@article {pmid38649742, year = {2024}, author = {Kaltenecker, D and Al-Maskari, R and Negwer, M and Hoeher, L and Kofler, F and Zhao, S and Todorov, M and Rong, Z and Paetzold, JC and Wiestler, B and Piraud, M and Rueckert, D and Geppert, J and Morigny, P and Rohm, M and Menze, BH and Herzig, S and Berriel Diaz, M and Ertürk, A}, title = {Virtual reality-empowered deep-learning analysis of brain cells.}, journal = {Nature methods}, volume = {}, number = {}, pages = {}, pmid = {38649742}, issn = {1548-7105}, support = {SFB 824//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 824//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 824//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1052//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TR 296//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 01KX2121//Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)/ ; 949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 2020 EKSE.23//Else Kröner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)/ ; }, abstract = {Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos[+] cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.}, } @article {pmid37479782, year = {2023}, author = {Fond, G and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Boyer, L}, title = {How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {5328-5336}, pmid = {37479782}, issn = {1476-5578}, mesh = {Humans ; *Schizophrenia/drug therapy/epidemiology ; Male ; Female ; Middle Aged ; Adult ; *Antipsychotic Agents/therapeutic use ; Cohort Studies ; Aged ; Comorbidity ; Antidepressive Agents/therapeutic use ; Anticonvulsants/therapeutic use ; Adolescent ; Young Adult ; }, abstract = {An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012-2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3-3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18-34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18-34-year-olds to reduce suicide rates.}, } @article {pmid38646373, year = {2024}, author = {Kani, V and Chander, V and Sonti, S and Manian, S and Vasudevan, S and Esakki, M and Grace Priyadarshini, S and Rajendran, K}, title = {A Rare and Intriguing Case Report of Metaplastic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e56619}, pmid = {38646373}, issn = {2168-8184}, abstract = {Metaplastic breast carcinoma (MBC) is a rare and aggressive subtype of breast cancer characterized by the presence of both epithelial and mesenchymal components within the tumor. Its clinical and radiological appearance is comparable to other types of breast cancer, but it grows rapidly. The diagnosis of metaplastic carcinoma is largely based on the epithelial origin of the cells confirmed by immunohistochemistry (IHC). Compared to invasive ductal carcinoma, metaplastic carcinoma has a worse overall survival rate. Any patient with a rapidly growing breast mass should be assessed with suspicion of sarcomatoid or metaplastic malignant neoplasm. We report this case due to its rarity and the complex nature of the disease.}, } @article {pmid38644311, year = {2024}, author = {Satoh, E and Innami, Y and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {4}, pages = {427-429}, pmid = {38644311}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy ; *Lung Neoplasms/secondary/drug therapy ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Time Factors ; Carcinoma, Ductal, Breast/secondary/therapy/drug therapy ; Mastectomy ; }, abstract = {We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer(invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).}, } @article {pmid38644310, year = {2024}, author = {Tanaka, Y and Ohshima, Y and Fukaya, Y and Hosoya, K and Wakahara, M}, title = {[Case Report of Occult Breast Cancer with Triple Negative Subtype].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {4}, pages = {421-423}, pmid = {38644310}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/surgery ; Mammography ; Ambulatory Care Facilities ; Axilla ; Biopsy, Fine-Needle ; Lymphatic Metastasis ; }, abstract = {A 61-year-old woman presented at a nearby clinic with a complaint of a mass in the right axilla. Initial imaging examinations, including mammography, ultrasonography, and breast MRI, did not reveal any obvious intramammary lesions, although a swollen lymph node was observed in the right axilla. Fine-needle aspiration cytology confirmed malignancy. Hence, a core needle biopsy was performed. The results indicated a suspected metastasis of invasive ductal carcinoma(ER-, PgR-, HER2-); however, the primary tumor could not be definitively determined. Despite an extensive whole-body examination, the primary tumor remained unidentified. Nonetheless, metastasis of occult breast cancer in the right axillary lymph node was postulated. Subsequent axillary dissection revealed metastases in only one lymph node. Taking the clinical findings into consideration, the patient was diagnosed with right occult breast cancer, and chemotherapy and radiotherapy were planned.}, } @article {pmid38638844, year = {2024}, author = {Zhou, H and Liu, D and Chen, L and Zhang, Y and Zhao, X and Ge, Y and Liu, M and Kong, T}, title = {Metastasis to the bladder from primary breast cancer: A case report and literature review.}, journal = {Oncology letters}, volume = {27}, number = {6}, pages = {249}, pmid = {38638844}, issn = {1792-1082}, abstract = {Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.}, } @article {pmid38628265, year = {2024}, author = {Chaane, N and Kuehnast, M and Rubin, G}, title = {An audit of breast cancer in patients 40 years and younger in two Johannesburg academic hospitals.}, journal = {SA journal of radiology}, volume = {28}, number = {1}, pages = {2772}, pmid = {38628265}, issn = {1027-202X}, abstract = {BACKGROUND: Breast cancer is the most common cancer in females, usually diagnosed after the age of 50 years. There is a perceived increase in breast cancer cases in young women in two public sector Johannesburg academic hospitals; however, there is a shortage of data to confirm this.

OBJECTIVES: This study aimed to assess data on breast cancer in young patients and determine any increase in the number of cases in patients 40 years and younger.

METHOD: A retrospective analysis of radiology and histopathology reports of patients 40 years and younger, seen at the radiology departments of two Johannesburg academic hospitals, was performed over a 5-year period. The frequency, histology and immunohistochemical results of breast cancer diagnoses were determined in patients with a Breast Imaging - Reporting and Data System (BI-RADS) classification of 4 or above.

RESULTS: Breast cancer was diagnosed in 73% of the total eligible 469 patients. The mean patient age was 34.35 years. Invasive ductal carcinoma was diagnosed in 83% (n = 283) of patients classified as BI-RADS 5 on imaging. Luminal A and B subtypes were the most common. The highest number of patients (n = 142) were seen in 2016 of which 92 had breast cancer.

CONCLUSION: In this very specific sample set, there was a lower number of breast cancer diagnoses in 2015 and then an increase of breast cancer diagnoses in young patients from 2016 to 2018.

CONTRIBUTION: Earlier breast cancer detection benefits the patient, their families and their reproductive ability. Knowledge of breast cancers in young patients can increase awareness, leading to effective, early diagnoses.}, } @article {pmid38633394, year = {2022}, author = {Evlice, O and Bektaş, M and Arık, Ö and Acet, A and Marim, F and Kaya, İ and Şener, A and Erarslan, S and Mistanoğlu, D and Ak, Ö}, title = {Antibiotic Use among Patients Hospitalized with COVID-19 and Treated in Three Different Clinics.}, journal = {Infectious diseases & clinical microbiology}, volume = {4}, number = {3}, pages = {199-205}, pmid = {38633394}, issn = {2667-646X}, abstract = {OBJECTIVE: In this study, we aimed to determine and compare the rates of empirical antibiotic use and duration between the chest diseases clinic (CDC), infectious disease clinic (IDC), and internal medicine clinic (IMC) among patients hospitalized because of COVID-19.

METHODS: This cross-sectional study was performed in a single university hospital. The study included all patients aged 18 years and older hospitalized with a PCR-confirmed COVID-19 between May 30, 2021, and August 30, 2021. Clinical and laboratory findings were recorded from the electronic medical records database.

RESULTS: The study included a total of 581 inpatients, of whom 310 (53.4%) were women. Of the 581 patients, 475 (81.8%) were prescribed antibiotics. The rate of antibiotic prescription was 71.6% for IDC, 88.5% for CDC, and 87.4% for IMC. The most commonly used antibiotic was moxifloxacin in all groups. The mean treatment duration was 8.9±6.16 days. The mean duration of antibiotic treatment was 11.1±5.90 days for CDC, 11.3±6.74 days for IMC, and 5.3 days±3.76 for IDC.

CONCLUSION: Patients with COVID-19 who were treated in IDC had a lower rate and shorter duration of antibiotic use compared to the other clinics. However, the rate of antibiotic prescription in all three groups was very high. Therefore, antimicrobial management programs should be meticulously conducted to reduce unnecessary antibiotic use.}, } @article {pmid38627759, year = {2024}, author = {Cipolla, C and Lupo, S and Grassi, N and Tutino, G and Greco, M and Eleonora, D and Gebbia, V and Valerio, MR}, title = {Correlation between sentinel lymph node biopsy and non-sentinel lymph node metastasis in patients with cN0 breast carcinoma: comparison of invasive ductal carcinoma and invasive lobular carcinoma.}, journal = {World journal of surgical oncology}, volume = {22}, number = {1}, pages = {100}, pmid = {38627759}, issn = {1477-7819}, mesh = {Humans ; Female ; Sentinel Lymph Node Biopsy ; Lymphatic Metastasis/pathology ; *Carcinoma, Lobular/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; *Breast Neoplasms/surgery/pathology ; *Sentinel Lymph Node/surgery/pathology ; Lymph Node Excision ; Lymph Nodes/pathology ; Axilla/pathology ; }, abstract = {BACKGROUND: Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1-2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC).

MATERIALS METHODS: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis.

RESULTS: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78-66.7%) compared to IDC (207/460 - 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs.

CONCLUSIONS: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1-2 positive SLNs still requires further investigation.}, } @article {pmid38624259, year = {2024}, author = {Petrakis, IL and Meshberg-Cohen, S and Nich, C and Kelly, MM and Claudio, T and Jane, JS and Pisani, E and Ralevski, E}, title = {Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.}, journal = {The American journal on addictions}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajad.13557}, pmid = {38624259}, issn = {1521-0391}, support = {1 I01 CX001517-01//VA MERIT grant, Division of Clinical Science Research and Development/ ; }, abstract = {BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine.

METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38).

RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study.

DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling.

SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.}, } @article {pmid38623464, year = {2024}, author = {Dye, A and Jhaveri, V and Ozdemir, S and Alkhasawneh, A and Hew, K}, title = {Recurrent invasive ductal carcinoma of the breast with metastasis to the uterine cervix: A case report.}, journal = {Case reports in women's health}, volume = {42}, number = {}, pages = {e00607}, pmid = {38623464}, issn = {2214-9112}, abstract = {This article presents a case of cervical metastasis from recurrence of invasive ductal carcinoma of the breast >20 years after initial diagnosis. The diagnosis was made after the patient presented with three months of intermittent post-menopausal vaginal spotting. She underwent palliative radiotherapy combined with chemotherapy and was disease free at the time of writing. Cervical metastasis of a primary breast cancer is extremely rare and can present with a variety of symptoms. This case report highlights the importance of life-long gynecologic care and surveillance in patients with a history of breast cancer.}, } @article {pmid38623446, year = {2024}, author = {Lue, M and Harrah, P and Shrestha, S and Wang, HT}, title = {Reconstruction after Resection of Undifferentiated Pleomorphic Sarcoma and Invasive Ductal Carcinoma in a Patient with Li-Fraumeni Syndrome.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {12}, number = {4}, pages = {e5737}, doi = {10.1097/GOX.0000000000005737}, pmid = {38623446}, issn = {2169-7574}, abstract = {This case exhibits a presentation of multiple primary malignancies in a patient with Li-Fraumeni syndrome, necessitating surgical excision and multistaged reconstruction. Due to Li-Fraumeni syndrome patients' predisposition to developing malignancies, management includes lifelong surveillance and aggressive treatment of cancers. Plastic surgeons can minimize damage to patient's quality of life by carrying out reconstruction in a thoughtful manner that maximizes function and considers a potential lifetime of future reconstructive needs.}, } @article {pmid38622289, year = {2024}, author = {Roy, S and Shanmugam, G and Rakshit, S and Pradeep, R and George, M and Sarkar, K}, title = {Exploring the immunomodulatory potential of Brahmi (Bacopa monnieri) in the treatment of invasive ductal carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {5}, pages = {115}, pmid = {38622289}, issn = {1559-131X}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, abstract = {Bacopa monnieri (L) Wettst, commonly known as Brahmi, stands as a medicinal plant integral to India's traditional medical system, Ayurveda, where it is recognized as a "medhya rasayana"-a botanical entity believed to enhance intellect and mental clarity. Its significant role in numerous Ayurvedic formulations designed to address conditions such as anxiety, memory loss, impaired cognition, and diminished concentration underscores its prominence. Beyond its application in cognitive health, Brahmi has historically been employed in Ayurvedic practices for the treatment of inflammatory diseases, including arthritis. In contemporary biomedical research, Bacopa monnieri can attenuate the release of pro-inflammatory cytokines TNF-α and IL-6 in animal models. However, there remains a paucity of information regarding Bacopa's potential as an anticancer agent, warranting further investigation in this domain. Based on previous findings with Brahmi (Bacopa monnieri), the current study aims to find out the role of Brahmi plant preparation (BPP) in immunomodulatory actions on IDC. Employing a specific BPP concentration, we conducted a comprehensive study using MTT assay, ELISA, DNA methylation analysis, Western blotting, ChIP, and mRNA profiling to assess BPP's immunomodulatory properties. Our research finding showed the role of BPP in augmenting the action of T helper 1 (TH1) cells which secreted interferon-γ (IFN-γ) which in turn activated cytotoxic T-lymphocytes (CTL) to kill the cells of IDC (*p < 0.05). Moreover, we found out that treatment with BPP not only increased the activities of tumor-suppressor genes (p53 and BRCA1) but also decreased the activities of oncogenes (Notch1 and DNAPKcs) in IDC (*p < 0.05). BPP had an immense significance in controlling the epigenetic dysregulation in IDC through the downregulation of Histone demethylation & Histone deacetylation and upregulation of Histone methylation and Histone acetylation (*p < 0.05). Our Chromatin immunoprecipitation (ChIP)-qPCR data showed BPP treatment increased percentage enrichment of STAT1 & BRCA1 (*p < 0.05) and decreased percentage enrichment of STAT3, STAT5 & NF ΚB (*p < 0.05) on both TBX21 and BRCA1 gene loci in IDC. In addition, BPP treatment reduced the hypermethylation of the BRCA1-associated-DNA, which is believed to be a major factor in IDC (*p < 0.05). BPP not only escalates the secretion of type 1 specific cytokines but also escalates tumor suppression and harmonizes various epigenetic regulators and transcription factors associated with Signal Transducer and Activator of Transcription (STAT) to evoke tumor protective immunity in IDC.}, } @article {pmid38621672, year = {2024}, author = {Sánchez-Dávila, JN and Verástegui, EL and Peña-Nieves, A and Allende-Pérez, SR}, title = {Integration of the geriatric palliative care in oncological care of elderly patient with cancer.}, journal = {Palliative & supportive care}, volume = {}, number = {}, pages = {1-9}, doi = {10.1017/S1478951524000294}, pmid = {38621672}, issn = {1478-9523}, abstract = {OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided.

METHODS: During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal.

RESULTS: The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population.

SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.}, } @article {pmid38618899, year = {2024}, author = {Kosie, JE and Lew-Williams, C}, title = {Infant-directed communication: Examining the many dimensions of everyday caregiver-infant interactions.}, journal = {Developmental science}, volume = {}, number = {}, pages = {e13515}, doi = {10.1111/desc.13515}, pmid = {38618899}, issn = {1467-7687}, support = {2004983//National Science Foundation SBE Postdoctoral Research Fellowship/ ; F32HD103439//National Institute of Child Health and Human Development/ ; R01HD095912//National Institute of Child Health and Human Development/ ; }, abstract = {Everyday caregiver-infant interactions are dynamic and multidimensional. However, existing research underestimates the dimensionality of infants' experiences, often focusing on one or two communicative signals (e.g., speech alone, or speech and gesture together). Here, we introduce "infant-directed communication" (IDC): the suite of communicative signals from caregivers to infants including speech, action, gesture, emotion, and touch. We recorded 10 min of at-home play between 44 caregivers and their 18- to 24-month-old infants from predominantly white, middle-class, English-speaking families in the United States. Interactions were coded for five dimensions of IDC as well as infants' gestures and vocalizations. Most caregivers used all five dimensions of IDC throughout the interaction, and these dimensions frequently overlapped. For example, over 60% of the speech that infants heard was accompanied by one or more non-verbal communicative cues. However, we saw marked variation across caregivers in their use of IDC, likely reflecting tailored communication to the behaviors and abilities of their infant. Moreover, caregivers systematically increased the dimensionality of IDC, using more overlapping cues in response to infant gestures and vocalizations, and more IDC with infants who had smaller vocabularies. Understanding how and when caregivers use all five signals-together and separately-in interactions with infants has the potential to redefine how developmental scientists conceive of infants' communicative environments, and enhance our understanding of the relations between caregiver input and early learning. RESEARCH HIGHLIGHTS: Infants' everyday interactions with caregivers are dynamic and multimodal, but existing research has underestimated the multidimensionality (i.e., the diversity of simultaneously occurring communicative cues) inherent in infant-directed communication. Over 60% of the speech that infants encounter during at-home, free play interactions overlap with one or more of a variety of non-speech communicative cues. The multidimensionality of caregivers' communicative cues increases in response to infants' gestures and vocalizations, providing new information about how infants' own behaviors shape their input. These findings emphasize the importance of understanding how caregivers use a diverse set of communicative behaviors-both separately and together-during everyday interactions with infants.}, } @article {pmid38617864, year = {2024}, author = {Park, SY and Lee, J and Park, JY and Kim, GC and Park, J and Cha, JG and Kim, HJ}, title = {Primary Invasive Ductal Carcinoma Arising in Axillary Accessory Breast: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {85}, number = {2}, pages = {421-427}, pmid = {38617864}, issn = {2951-0805}, abstract = {Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.}, } @article {pmid38611640, year = {2024}, author = {Sato, A and Fujioka, T and Onishi, I and Yamaga, E and Katsuta, L and Kubota, K and Kumaki, Y and Ishiba, T and Oda, G and Tateishi, U}, title = {Arterial Calcification Disappearance in Breast Imaging: A Key Indicator for Transition to Invasive Ductal Carcinoma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611640}, issn = {2075-4418}, abstract = {A woman in her 70s, initially suspected of having fibroadenoma due to a well-defined mass in her breast, underwent regular mammography and ultrasound screenings. Over several years, no appreciable alterations in the mass were observed, maintaining the fibroadenoma diagnosis. However, in the fourth year, an ultrasound indicated slight enlargement and peripheral irregularities in the mass, even though the mammography images at that time showed no alterations. Interestingly, mammography images over time showed the gradual disappearance of previously observed arterial calcification around the mass. Pathological examination eventually identified the mass as invasive ductal carcinoma. Although the patient had breast tissue arterial calcification typical of atherosclerosis, none was present around the tumor-associated arteries. This case highlights the importance of monitoring arterial calcification changes in mammography, suggesting that they are crucial indicators in breast cancer diagnosis, beyond observing size and shape alterations.}, } @article {pmid38611095, year = {2024}, author = {Bensenane, R and Beddok, A and Lesueur, F and Fourquet, A and Warcoin, M and Le Mentec, M and Cavaciuti, E and Le Gal, D and Eon-Marchais, S and Andrieu, N and Stoppa-Lyonnet, D and Kirova, Y}, title = {Safety of the Breast Cancer Adjuvant Radiotherapy in Ataxia-Telangiectasia Mutated Variant Carriers.}, journal = {Cancers}, volume = {16}, number = {7}, pages = {}, pmid = {38611095}, issn = {2072-6694}, abstract = {The Ataxia-Telangiectasia Mutated (ATM) gene is implicated in DNA double-strand break repair. Controversies in clinical radiosensitivity remain known for monoallelic carriers of the ATM pathogenic variant (PV). An evaluation of the single-nucleotide polymorphism (SNP) rs1801516 (G-A) showed different results regarding late subcutaneous fibrosis after breast radiation therapy (RT). The main objective of this study was to evaluate acute and late toxicities in carriers of a rare ATM PV or predicted PV and in carriers of minor allele A of rs1801516 facing breast RT. Fifty women with localized breast cancer treated with adjuvant RT between 2000 and 2014 at Institut Curie were selected. Acute and late toxicities in carriers of a rare PV or predicted PV (n= 9), in noncarriers (n = 41) and in carriers of SNP rs1801516 (G-A) (n = 8), were examined. The median age at diagnosis was 53 years old and 82% of patients had an invasive ductal carcinoma and 84% were at clinical stage I-IIB. With a median follow-up of 13 years, no significant difference between carriers and noncarriers was found for acute toxicities (p > 0.05). The same results were observed for late toxicities without an effect from the rs1801516 genotype on toxicities. No significant difference in acute or late toxicities was observed between rare ATM variant carriers and noncarriers after breast RT for localized breast cancer.}, } @article {pmid38609794, year = {2024}, author = {Weed, C and Wang, T and Mohan, SC and Wang, X and Tseng, J and Hu, T and Jaswinder, J and Boyle, MK and Amersi, F and Giuliano, A and Chung, A}, title = {Comparison of Clinical Breast Exam to Breast MRI Surveillance in Patients Following Nipple-Sparing Mastectomy.}, journal = {Clinical breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clbc.2024.03.011}, pmid = {38609794}, issn = {1938-0666}, abstract = {BACKGROUND: Nipple sparing mastectomy (NSM) is increasingly being performed for patients with breast cancer. However, optimal postoperative surveillance has not been defined.

METHODS: A prospectively maintained database identified patients with in-situ and invasive cancer who underwent NSM between 2007-2021. Clinical data on postoperative breast surveillance and interventions were collected. Patients who had MRI surveillance versus clinical breast exam (CBE) alone were compared with respect to tumor characteristics, recurrence, and survival.

RESULTS: A total of 483 NSMs were performed on 399 patients. 255 (63.9%) patients had invasive ductal carcinoma, 31 (7.8%) invasive lobular carcinoma, 92 (23.1%) DCIS, 6 (1.5%) mixed ductal and lobular carcinoma, 9 (2.3%) others, and 6 (1.5%) unknown. Postoperatively, 265 (66.4%) patients were followed with CBE alone and 134 (33.6%) had surveillance MRIs. At a median follow-up of 33 months, 20 patients (5.0%) developed in-breast recurrence, 6 patients had (1.5%) an axillary recurrence, and 28 with (7.0%) distant recurrence. 14 (53.8%) LRR were detected in the CBE group and 12 (46.2%) were detected in the MRI group (P = .16). Overall survival (OS) was 99%, with no difference in OS between patients who had CBE alone versus MRI (P = .46). MRI was associated with higher biopsy rates compared to CBE alone (15.8% vs. 7.8%, P = .01).

CONCLUSIONS: Compared to CBE alone, the use of screening MRI following NSM results in higher rate of biopsy and no difference in overall survival.}, } @article {pmid38605427, year = {2024}, author = {Wang, K and Schober, L and Fischer, A and Bechmann, N and Maurer, J and Peischer, L and Reul, A and Hantel, C and Reincke, M and Beuschlein, F and Robledo, M and Mohr, H and Pellegata, NS and Schilbach, K and Knösel, T and Ilmer, M and Angele, M and Kroiss, M and Maccio, U and Broglie-Däppen, M and Vetter, D and Lehmann, K and Pacak, K and Grossman, AB and Auernhammer, CJ and Zitzmann, K and Nölting, S}, title = {Opposing effects of cannabidiol in patient-derived neuroendocrine tumor, pheochromocytoma/paraganglioma primary cultures.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgae241}, pmid = {38605427}, issn = {1945-7197}, abstract = {CONTEXT: Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (together PPGLs) are still limited. In recent years, anti-tumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs.

OBJECTIVE: Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines.

METHODS: We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at two centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed.

RESULTS: We found opposing effects of 5 µM CBD: significant anti-tumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of anti-tumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (p = 0.042). Of the cluster 2-related tumors, NF1 PPGLs showed strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant anti-tumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures, significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures.

CONCLUSIONS: We suggest a potential novel treatment option for some NETs/PPGLs, but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients, and possibly as health supplements.}, } @article {pmid38599926, year = {2024}, author = {Sefidbakht, S and Beizavi, Z and Kanaani Nejad, F and Pishdad, P and Sadighi, N and Ghoddusi Johari, M and Bijan, B and Tahmasebi, S}, title = {Association of imaging and pathological findings of breast cancer in very young women: Report of a twenty-year retrospective study.}, journal = {Clinical imaging}, volume = {110}, number = {}, pages = {110094}, doi = {10.1016/j.clinimag.2024.110094}, pmid = {38599926}, issn = {1873-4499}, abstract = {PURPOSE: In this study, we aimed to assess the new trends in characteristics, molecular subtypes, and imaging findings of breast cancer in very young women.

METHODS: We retrospectively reviewed the database of a primary breast cancer referral center in southern Iran in 342 cases of 30-year-old or younger women from 2001 to 2020. Pathologic data, including nuclear subtype and grade, tumor stage, presence of in situ cancer, imaging data including lesion type in mammogram and ultrasound, and treatment data were recorded. Descriptive statistics were applied. Differences between categorical values between groups were compared using Pearson's Chi-square test.

RESULTS: The mean age was 27.89 years. The tumor type was invasive ductal carcinoma in 82 % of cases. Fourteen patients (4.4 %) had only in situ cancer, and 170 patients had in situ components (49.7 %). Molecular subtypes were available in 278 patients, including 117 (42.1 %) Luminal A, 64 (23.0 %) Luminal B, 58 (20.9 %) triple negative, and 39 (14 %) HER2 Enriched. In those with mammograms available, 63 (30.1 %) had no findings, 53 (25.3 %) had mass, 27 (12.9 %) had asymmetry, whether focal or global, 21 (10 %) had microcalcifications solely, and 45 (21.5 %) had more than one finding. Microcalcifications were significantly more common in Luminal cancers than HER2 and triple-negative cancers (p = 0.041).

CONCLUSION: Our study shows the most common subtype to be Luminal A cancer, with 74 % of the tumors being larger than 2 cm at the time of diagnosis. Irregular masses with non-circumscribed margins were the most common imaging findings.}, } @article {pmid38603004, year = {2022}, author = {Gruneau Brulin, J and Shaver, PR and Mikulincer, M and Granqvist, P}, title = {Attachment in the time of COVID-19: Insecure attachment orientations are associated with defiance of authorities' guidelines during the pandemic.}, journal = {Journal of social and personal relationships}, volume = {39}, number = {8}, pages = {2528-2548}, pmid = {38603004}, issn = {0265-4075}, abstract = {Previous research has linked people's relational attachment orientations to emotional reactions and coping during crises, and to social trust and trust in societal institutions. The COVID-19 pandemic is a global crisis for which collective efforts, such as social distancing, are necessary to stop the spread of the virus. During previous pandemics, people high in trust have typically adhered to such efforts. In the present study, we investigated whether attachment orientations were related to people's adherence to authorities' guidelines to stop the spread of COVID-19. We also tested whether previous mediational findings-linking attachment-related avoidance to welfare state trust via social trust-would replicate. We used a web-based survey of 620 participants. Our findings showed that attachment-related anxiety was linked to low adherence to social distancing regulations. This finding was especially noteworthy because high attachment-anxious participants also experienced more negative emotions, yet negative emotions were generally linked to high adherence. Thus, people higher in attachment anxiety seem to have more difficulties in avoiding social situations despite heightened risk of catching and spreading the virus. In addition, attachment-related avoidance was negatively related to adherence and to welfare state trust, and its effects on welfare state trust were statistically mediated by low social trust.}, } @article {pmid38597082, year = {2024}, author = {Wang, S and Zhou, Z and Yuan, Q and Yue, L and Yang, S}, title = {Trueness evaluation of three intraoral scanners for the recording of maximal intercuspal position.}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {42}, number = {2}, pages = {227-233}, doi = {10.7518/hxkq.2024.2023277}, pmid = {38597082}, issn = {2618-0456}, mesh = {Humans ; *Molar ; *Incisor ; Mandible ; Maxilla ; Computer-Aided Design ; Imaging, Three-Dimensional ; Dental Impression Technique ; }, abstract = {OBJECTIVES: This clinical study aimed to assess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position (MIP) to provide a reference for clinical practice.

METHODS: Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited. For the control group, facebow transferring procedures were performed, and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator, which were then scanned with a laboratory scanner to obtain digital cast data. For the experimental groups, three intraoral scanners (Trios 3, Carestream 3600, and Aoralscan 3) were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers. Subsequently, measurement points were marked on the control group's digital casts at the central incisors, canines, and first molars, and corresponding distances between these points on the maxillary and mandibular casts were measured to calculate the sum of measured distances (DA). Distances between measurement points in the incisor (DI), canine (DC), and first molar (DM) regions were also calculated. The control group's maxillary and mandibular digital casts with the added measurement points were aligned with the experimental group's casts, and DA, DI, DC, and DM values of the aligned control casts were determined. Statistical analysis was performed on DA, DI, DC, and DM obtained from both the control and experimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP.

RESULTS: In the control group, DA, DI, DC, and DM values were (39.58±6.40), (13.64±3.58), (14.91±2.85), and (11.03±1.56) mm. The Trios 3 group had values of (38.99±6.60), (13.42±3.66), (14.55±2.87), and (11.03±1.69) mm. The Carestream 3600 group showed values of (38.57±6.36), (13.56±3.68), (14.45±2.85), and (10.55±1.41) mm, while the Aoralscan 3 group had values of (38.16±5.69), (13.03±3.54), (14.23±2.59), and (10.90±1.54) mm. Analysis of variance revealed no statistically significant differences between the experimental and control groups for overall deviation DA (P=0.96), as well as local deviations DI (P=0.98), DC (P=0.96), and DM (P=0.89).

CONCLUSIONS: With standardized scanning protocols, the three intraoral scanners demonstrated comparable trueness to traditional methods in recording MIP, fulfilling clinical requirements.}, } @article {pmid38592540, year = {2024}, author = {Rukhsana, and Supty, AT and Hussain, M and Lee, Y}, title = {STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {38592540}, issn = {1573-7217}, support = {2022R1F1A1069631//National Research Foundation of Korea/ ; }, abstract = {PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.

METHODS: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis.

RESULTS: Increased STK3 expression in breast cancer was significantly associated with higher pathological cancer stages, and a different expression level was observed in the intrinsic subtypes of breast cancer. Kaplan-Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p < 0.05). The multivariate analysis unveiled a strong correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34-0.94, p = 0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42-0.92, p = 0.017) for all deceased patients. Additionally, in the METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64-0.91, p = 0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical significance (FDR < 0.25 and p < 0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3.

CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.}, } @article {pmid38586701, year = {2024}, author = {Nair, N and More, A and Singh, BR and Wadkar, A and Tilak, P}, title = {A Successful Pregnancy Following Intracytoplasmic Sperm Injection in a Breast Cancer Survivor: A Case Report.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e55756}, pmid = {38586701}, issn = {2168-8184}, abstract = {This report documents the case of a 36-year-old female diagnosed with stage I invasive ductal carcinoma of the left breast who, alongside her 39-year-old husband, sought fertility assistance at our center due to primary infertility. Having survived cancer twice in the span of their seven-year marriage, the couple faced the challenge of overcoming both the repercussions of cancer treatment and difficulties in conceiving. Initial attempts through three intrauterine insemination (IUI) cycles proved unsuccessful, leading the couple to opt for in vitro fertilization (IVF). The fertility assessment of the husband revealed the presence of several pus cells and a high sperm DNA fragmentation index (DFI). To address this, a medication regimen was administered to improve sperm quality. Concurrently, the female underwent controlled ovarian stimulation (COS) with the anti-estrogen agent letrozole to mitigate the risk of estrogen surges that could compromise her health. Subsequently, oocytes were retrieved from the female, and intracytoplasmic sperm injection (ICSI) was used to facilitate fertilization with her husband's sperm. Following successful embryo development, the patient underwent embryo transfer (ET), resulting in a positive beta-human chorionic gonadotropin (beta-hCG) result, signifying a successful conception. This case report highlights the intricate challenges faced by individuals with a history of breast cancer, emphasizing the delicate balance required in managing infertility in such circumstances. The described approach, involving personalized treatments and meticulous care, underscores the possibility of achieving successful conception for females struggling with fertility issues post-cancer survival. The documented journey serves as a testament to the resilience of individuals facing the dual challenges of cancer survival and infertility, offering insights into the complexities of their reproductive healthcare.}, } @article {pmid38578135, year = {2024}, author = {Zheng, MY and Jin, ZB and Ma, ZZ and Gu, ZG and Zhang, J}, title = {Photo-Curable 3D Printing of Circularly Polarized Afterglow Metal-Organic Framework Monoliths.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e2313749}, doi = {10.1002/adma.202313749}, pmid = {38578135}, issn = {1521-4095}, support = {2022YFA1503300//National Key Research and Development Program of China/ ; Y2022081//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; 2022J06031//Natural Science Foundation of Fujian Province/ ; 2023T3003//STS Project of Fujian-CAS/ ; 2023T3052//STS Project of Fujian-CAS/ ; }, abstract = {Developing coordination complexes (such as metal-organic frameworks, MOFs) with circularly polarized luminescence (CPL) is currently attracting tremendous attention and remains a significant challenge in achieving MOF with circularly polarized afterglow. Herein, MOFs-based circularly polarized afterglow is first reported by combining the chiral induction approach and tuning the afterglow times by using the auxiliary ligands regulation strategy. The obtained chiral R/S-ZnIDC, R/S-ZnIDC(bpy), and R/S-ZnIDC(bpe)(IDC = 1H-Imidazole-4,5-dicarboxylate, bpy = 4,4'-Bipyridine, bpe = trans-1,2-Bis(4-pyridyl) ethylene) containing a similar structure unit display different afterglow times with 3, 1, and <0.1 s respectively which attribute to that the longer auxiliary ligand hinders the energy transfer through the hydrogen bonding. The obtained chiral complexes reveal a strong chiral signal, obvious photoluminescence afterglow feature, and strong CPL performance (glum up to 3.7 × 10[-2]). Furthermore, the photo-curing 3D printing method is first proposed to prepare various chiral MOFs based monoliths from 2D patterns to 3D scaffolds for anti-counterfeiting and information encryption applications. This work not only develops chiral complexes monoliths by photo-curing 3D printing technique but opens a new strategy to achieve tunable CPL afterglow in optical applications.}, } @article {pmid38585820, year = {2024}, author = {Tang, X and Prodduturi, N and Thompson, KJ and Weinshilboum, R and O'Sullivan, CC and Boughey, JC and Tizhoosh, HR and Klee, EW and Wang, L and Goetz, MP and Suman, V and Kalari, KR}, title = {OmicsFootPrint: a framework to integrate and interpret multi-omics data using circular images and deep neural networks.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.21.586001}, pmid = {38585820}, abstract = {BACKGROUND: The integration and interpretation of multi-omics data are crucial in elucidating the pathophysiological mechanisms of complex diseases. While Deep Neural Networks (DNNs) and Graph Neural Networks (GNNs) have revolutionized the analysis of such data in cancer and neurodegenerative diseases, there remains a critical need for improved multi-omics analytic methodologies.

METHODS: We developed OmicsFootPrint, a novel framework for transforming multi-omics data into two-dimensional circular images for each sample, enabling intuitive representation and analysis.Utilizing DNNs for analysis, this framework incorporates the SHapley Additive exPlanations (SHAP) algorithm for model interpretation. We benchmarked OmicsFootPrint performance with data sets from The Cancer Genome Atlas (TCGA); we classified subtypes of lung cancer and breast cancer, specifically the PAM50 subtype and histological classifications. Additionally, we applied OmicsFootPrint to predict drug response data in cancer cell lines.

RESULTS: Evaluation of lung cancer subtypes using TCGA data sets, OmicsFootPrint achieved an average Area Under Curve (AUC) of over 0.90 for distinguishing between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) subtypes. Notably, the EfficientNetV2 model reached an AUC of 0.98±0.02. For the TCGA BRCA (breast cancer) PAM50 subtype classification, encompassing Luminal A, Luminal B, Basal, and HER2 subtypes (836 samples in total), the framework reported an average AUC of 0.83±0.07. Furthermore, the application of OmicsFootPrint to the BRCA data set for distinguishing between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) showed an average AUC of 0.87±0.04 with four-omics datatypes.Additionally, in drug response studies, OmicsFootPrint outperformed published algorithms, achieving the highest average AUC of 0.74 across all data sets. OmicsFootPrint also demonstrated robust performance with reduced training sample sizes.

CONCLUSIONS: OmicsFootPrint represents a significant advancement, offering a comprehensive, efficient, and interpretable framework for multi-omics data analysis. Its innovative approach in transforming extensive multi-omics data sets into compact, circular images not only reduces memory requirements but also enhances the interpretability of complex biological data. This approach facilitates personalized treatment strategies and enriches our understanding of disease mechanisms, marking a significant step forward in the field of multi-omics research.}, } @article {pmid38578876, year = {2024}, author = {Rodriguez, GF and Shah, A and Maderal, AD}, title = {Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {61-64}, doi = {10.3233/BD-230053}, pmid = {38578876}, issn = {1558-1551}, mesh = {Female ; Humans ; Aged ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Trastuzumab/adverse effects ; Quinazolines/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Oxazoles ; *Pyridines ; }, abstract = {BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.

OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.

RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.

CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.}, } @article {pmid38577141, year = {2024}, author = {Sukhija, S and Purohit, P and Pareek, P and Garg, PK and Vishnoi, JR and Elhence, PA and Varthya, SB and Sharma, P and Ambwani, S and Charan, J}, title = {Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.}, journal = {Indian journal of clinical biochemistry : IJCB}, volume = {39}, number = {2}, pages = {214-220}, pmid = {38577141}, issn = {0970-1915}, abstract = {Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.}, } @article {pmid38576929, year = {2024}, author = {Jamal, O and Makhchoune, M and Laidi, A and Misbahi, T and Haouas, MY and Chellaoui, A and Bertal, A and Hilmani, S and Ibahiouine, K and Naja, A and Lakhder, A}, title = {Rupture of a dermoid cyst in the subarachnoid space: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {4}, pages = {2366-2369}, pmid = {38576929}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.

CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.

CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.

CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.}, } @article {pmid38571894, year = {2024}, author = {Maiti, S and Nayak, S and Hebbar, KD and Pendem, S}, title = {Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {91}, pmid = {38571894}, issn = {2046-1402}, mesh = {Female ; Humans ; *Carcinoma, Lobular/diagnostic imaging/pathology ; Pilot Projects ; Retrospective Studies ; Radiomics ; *Breast Neoplasms/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).

METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.

RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.

CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.}, } @article {pmid38570490, year = {2024}, author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J}, title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {83}, pmid = {38570490}, issn = {2059-3635}, support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.}, } @article {pmid38561526, year = {2024}, author = {Foesleitner, O and Sulaj, A and Sturm, V and Kronlage, M and Preisner, F and Kender, Z and Bendszus, M and Szendroedi, J and Heiland, S and Schwarz, D}, title = {Diffusion tensor imaging in anisotropic tissues: application of reduced gradient vector schemes in peripheral nerves.}, journal = {European radiology experimental}, volume = {8}, number = {1}, pages = {37}, pmid = {38561526}, issn = {2509-9280}, support = {SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1118//Deutsche Forschungsgemeinschaft/ ; SFB 1158//Deutsche Forschungsgemeinschaft/ ; SFB 1158//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Diffusion Tensor Imaging/methods ; Anisotropy ; *Diabetes Mellitus, Type 2 ; Peripheral Nerves/diagnostic imaging ; Diffusion Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: In contrast to the brain, fibers within peripheral nerves have distinct monodirectional structure questioning the necessity of complex multidirectional gradient vector schemes for DTI. This proof-of-concept study investigated the diagnostic utility of reduced gradient vector schemes in peripheral nerve DTI.

METHODS: Three-Tesla magnetic resonance neurography of the tibial nerve using 20-vector DTI (DTI20) was performed in 10 healthy volunteers, 12 patients with type 2 diabetes, and 12 age-matched healthy controls. From the full DTI20 dataset, three reduced datasets including only two or three vectors along the x- and/or y- and z-axes were built to calculate major parameters. The influence of nerve angulation and intraneural connective tissue was assessed. The area under the receiver operating characteristics curve (ROC-AUC) was used for analysis.

RESULTS: Simplified datasets achieved excellent diagnostic accuracy equal to DTI20 (ROC-AUC 0.847-0.868, p ≤ 0.005), but compared to DTI20, the reduced models yielded mostly lower absolute values of DTI scalars: median fractional anisotropy (FA) ≤ 0.12; apparent diffusion coefficient (ADC) ≤ 0.25; axial diffusivity ≤ 0.96, radial diffusivity ≤ 0.07). The precision of FA and ADC with the three-vector model was closest to DTI20. Intraneural connective tissue was negatively correlated with FA and ADC (r ≥ -0.49, p < 0.001). Small deviations of nerve angulation had little effect on FA accuracy.

CONCLUSIONS: In peripheral nerves, bulk tissue DTI metrics can be approximated with only three predefined gradient vectors along the scanner's main axes, yielding similar diagnostic accuracy as a 20-vector DTI, resulting in substantial scan time reduction.

RELEVANCE STATEMENT: DTI bulk tissue parameters of peripheral nerves can be calculated with only three predefined gradient vectors at similar diagnostic performance as a standard DTI but providing a substantial scan time reduction.

KEY POINTS: • In peripheral nerves, DTI parameters can be approximated using only three gradient vectors. • The simplified model achieves a similar diagnostic performance as a standard DTI. • The simplified model allows for a significant acceleration of image acquisition. • This can help to introduce multi-b-value DTI techniques into clinical practice.}, } @article {pmid38560226, year = {2024}, author = {Lee, CP and Hashimoto, M}, title = {Prediction of textural properties of 3D-printed food using response surface methodology.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e27658}, doi = {10.1016/j.heliyon.2024.e27658}, pmid = {38560226}, issn = {2405-8440}, abstract = {3D printing has enabled modifying internal structures of the food affecting textural properties, but predicting desired texture remains challenging. To overcome this challenge, the use of response surface methodology (RSM) was demonstrated to develop empirical models relating 3D printing parameters to textural properties using aqueous inks containing cricket powders as a model system. Regression models were established for our key textural properties (i.e., hardness (H), adhesiveness (A), cohesiveness (C), and springiness (S)) in response to three 3D printing parameters: infill percentage (i), layer height (h), and print speed (s). Our developed model successfully predicted the 3D printing parameters to achieve the intended textural properties using a multi-objective optimization framework. The predicted limits for H, A, C, and S were 0.66-5.39 N, 0.01-12.43 mJ, 0.01-1.05, and 0-19.20 mm, respectively. To validate our models, we simulated the texture of other food using our model ink and achieved high accuracy for H (99%), C (82%), and S (87%). This work highlights a simple way to 3D-print foods with spatially different textures and materials, unlocking the full potential of 3D printing technology for manufacturing a range of customized foods.}, } @article {pmid38558414, year = {2024}, author = {Han, LK and Lee, J and Dodelzon, K and Towne, WS and Zhou, XK and Ginter, PS and Marti, JL}, title = {Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.}, journal = {World journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1002/wjs.12107}, pmid = {38558414}, issn = {1432-2323}, abstract = {BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS.

METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging.

RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1).

CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.}, } @article {pmid38556289, year = {2024}, author = {Nagai, N and Ogata, F and Kadowaki, R and Deguchi, S and Otake, H and Nakazawa, Y and Misra, M and Kawasaki, N}, title = {Design of an Oral Tablet Containing Furosemide Nanoparticles with Elevated Bioavailability.}, journal = {Journal of oleo science}, volume = {73}, number = {4}, pages = {563-571}, doi = {10.5650/jos.ess23229}, pmid = {38556289}, issn = {1347-3352}, abstract = {The solubility and permeability of the Biopharmaceutics Classification System (BCS) class IV drugs, such as furosemide (FUR), are low. Thus, the oral bioavailability of these drugs needs to be augmented. Here, we aimed to design orally disintegrating tablets containing FUR nanoparticles to improve bioavailability after oral administration. The FUR nanoparticles were generated by bead-milling in water containing 0.5% methylcellulose and 0.5% 2-hydroxypropyl-β-cyclodextrin (w/w%). Particle size was approximately 47-350 nm (mean particle size, 188 nm). An orally disintegrating tablet (FUR-NP tablet) comprising FUR nanoparticles (1%) was successfully produced by employing suspensions outlined above that incorporated additives (4% D-mannitol, 0.4% polyvinylpyrrolidone, and 16% gum Arabic, w/w%), followed by freeze-drying. The FUR-NP tablet disaggregated after only 5 s in water, liberating nano-sized FUR particles (172 nm). Experiments using rats showed the absorption of the FUR-NP tablet was significantly improved by comparison with a FUR tablet containing microparticles. In summary, the orally disintegrating tablet containing FUR nanoparticles markedly enhanced the bioavailability of FUR. We anticipate this formulation will also improve the bioavailability of other BCS class IV drugs.}, } @article {pmid38554305, year = {2024}, author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P}, title = {Outcomes of the patients with metastatic male breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {1}, pages = {98-102}, doi = {10.4103/jcrt.jcrt_1829_22}, pmid = {38554305}, issn = {1998-4138}, abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).

METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.

RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.

CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.}, } @article {pmid38553788, year = {2024}, author = {Dreindl, R and Bolsa-Ferruz, M and Fayos-Sola, R and Padilla Cabal, F and Scheuchenpflug, L and Elia, A and Amico, A and Carlino, A and Stock, M and Grevillot, L}, title = {Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.}, journal = {Journal of applied clinical medical physics}, volume = {}, number = {}, pages = {e14328}, doi = {10.1002/acm2.14328}, pmid = {38553788}, issn = {1526-9914}, abstract = {PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.

METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.

RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated.

CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.}, } @article {pmid38548533, year = {2024}, author = {Bai, L and You, C and Zhou, J and Xie, L and Zhu, X and Chang, C and Zhi, W}, title = {Quantitative Analysis of Shear Wave Elastography and US-Guided Diffuse Optical Tomography for Evaluating Biological Characteristics of Breast Cancer.}, journal = {Academic radiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.acra.2024.03.006}, pmid = {38548533}, issn = {1878-4046}, abstract = {RATIONALE AND OBJECTIVES: Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer.

MATERIALS AND METHODS: A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (Emax), Mean Elasticity (Emean), Standard Deviation of Elasticity (Esd), and Area Ratio were measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics.

RESULTS: Lesions in patient groups with ER-, PR-, HER2 + , high Ki67, LVI+ , and ALN+ exhibited higher THC, Emax, and Esd compared to groups with ER+ , PR+ , HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with Smax (r = 0.340, P < 0.001), Emax (r = 0.339, P < 0.001), Emean (r = 0.201, P = 0.003), and Esd (r = 0.313, P < 0.001).

CONCLUSION: US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with Emax, Emean, and Esd.}, } @article {pmid38545425, year = {2024}, author = {Magnoni, F and Corso, G and Maisonneuve, P and Bianchi, B and Accardo, G and Sangalli, C and Massari, G and Rotili, A and Nicosia, L and Pesapane, F and Montagna, E and Mazzarol, G and Galimberti, V and Veronesi, P and Curigliano, G}, title = {Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102552}, pmid = {38545425}, issn = {2589-5370}, abstract = {BACKGROUND: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria.

METHODS: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score.

FINDINGS: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population.

INTERPRETATION: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment.

FUNDING: Umberto Veronesi Foundation.}, } @article {pmid38539179, year = {2024}, author = {Esmat, E and Haidary, AM and Saadaat, R and Rizvi, SN and Aleena, S and Haidari, M and Hofiani, SMS and Hussaini, N and Hakimi, A and Khairy, A and Abdul-Ghafar, J}, title = {Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {388}, pmid = {38539179}, issn = {1471-2407}, abstract = {BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.

METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.

RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.

CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.}, } @article {pmid38536377, year = {2022}, author = {Harwood-Gross, A and Weltman, A and Kanat-Maymon, Y and Pat-Horenczyk, R and Brom, D}, title = {Peace of mind: Promoting psychological growth and reducing the suffering of combat veterans.}, journal = {Military psychology : the official journal of the Division of Military Psychology, American Psychological Association}, volume = {34}, number = {6}, pages = {668-678}, pmid = {38536377}, issn = {1532-7876}, abstract = {The Peace of Mind (POM) program was designed to enable combat veterans in Israel to process their combat experience, address difficulties in the transition to civilian life and facilitate psychological growth as a result of their military experience. During the course of the program, 1068 participants were studied at four time points. Post-traumatic symptoms were measured using the PTSD checklist for DSM-5 (PCL-5), and post-traumatic growth (PTG) was measured using the Post Traumatic Growth Inventory (PTGI). Multilevel Modeling (MLM) was used to assess symptom and psychological trajectories for all participants and for those who began with and without PTSD symptoms, respectively. The results demonstrated that those who began the program with elevated PTSD symptoms experienced a significant reduction in PTSD symptoms following the completion of the intensive element of the program. Additionally, all participants demonstrated an increase in PTG following the intensive section of the program and this was maintained throughout follow-up. The findings indicate that the POM program is beneficial in relation to both positive and negative outcomes of traumatic military experiences though it is clear that the transition from combat to civilian life is more complex than the current measures identify and that further research needs to examine the distinct lifestyle and functional changes which occur following the program.}, } @article {pmid38534445, year = {2024}, author = {Rapoport, R and Greenberg, A and Yakhini, Z and Simon, I}, title = {A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.}, journal = {Biology}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/biology13030175}, pmid = {38534445}, issn = {2079-7737}, abstract = {Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, large H3K9me3 and H3K27me3 domains, HiC compartments and lamina-associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNA) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.}, } @article {pmid38530283, year = {2024}, author = {Matta, L and Blaas, L and Gibis, C and Guerra, J}, title = {Functions require junctions: endurance exercise protects from age-induced alterations of the neuromuscular system.}, journal = {The Journal of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/JP286232}, pmid = {38530283}, issn = {1469-7793}, } @article {pmid38527731, year = {2024}, author = {Aksu, A and Zeynep Gülsüm, G and Küçüker, KA and Alacacıoğlu, A and Turgut, B}, title = {Intra and peritumoral PET radiomics analysis to predict the pathological response in breast cancer patients receiving neoadjuvant chemotherapy.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {}, number = {}, pages = {500002}, doi = {10.1016/j.remnie.2024.500002}, pmid = {38527731}, issn = {2253-8089}, abstract = {OBJECTIVE: The aim of our study was to evaluate the contribution of 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) radiomic data obtained from both the tumoral and peritumoral area in predicting pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC).

METHODS: Female patients with a diagnosis of invasive ductal carcinoma who received NAC were evaluated retrospectively. The volume of interest (VOI) of the primary tumor (VOI-T) was manually segmented, then a voxel-thick VOI was added around VOI-T to define the peritumoral area (VOI-PT). Morphological, intensity-based, histogram and texture parameters were obtained from VOIs. The patients were divided into two groups as pCR and non-complete pathological response (npCR). A "radiomic model" was created with only radiomic features, and a "patho-radiomic model" was created using radiomic features and immunohistochemical data.

RESULTS: Of the 66 patients included in the study, 21 were in the pCR group. The only statistically significant feature from the primary tumor among patients with pCR and npCR was Morphological_Compacity-T (AUC: 0.666). Between response groups, a significant difference was detected in 2 morphological, 1 intensity, 4 texture features from VOI-PT; no correlation was found between Morphological_Compacity-PT and NGTDM_contrast-PT. The obtained radiomic model's sensitivity and accuracy values were calculated as 61.9% and 75.8%, respectively (AUC: 0.786). When HER2 status was added, sensitivity and accuracy values of the patho-radiomic model increased to 85.7% and 81.8%, respectively (AUC: 0.903).

CONCLUSIONS: Evaluation of PET peritumoral radiomic features together with the primary tumor, rather than just the primary tumor, provides a better prediction of the pCR to NAC in patients with breast cancer.}, } @article {pmid38526962, year = {2024}, author = {Hauschildt, KE and Messersmith, J and Iwashyna, TJ}, title = {Inequities in Indirect Cost Rates Between Historically Black Colleges and Universities and Other Institutions.}, journal = {Academic medicine : journal of the Association of American Medical Colleges}, volume = {}, number = {}, pages = {}, doi = {10.1097/ACM.0000000000005717}, pmid = {38526962}, issn = {1938-808X}, abstract = {PURPOSE: Federal research grants provide support for the indirect costs (IDCs) of research infrastructure that are not specific to particular research projects but are nonetheless essential to enable research. Institutions independently negotiate IDC rates. The authors sought to identify whether inequities exist in negotiated IDC rates between historically Black colleges and universities (HBCUs) and other universities (non-HBCUs).

METHOD: In 2023, the authors analyzed mean negotiated IDC rates between the top 20 HBCUs (in fiscal year [FY] 2021 research expenditures) and 3 non-HBCU comparison groups: the top 40 non-HBCUs in FY 2021 research expenditures, metropolitan statistical area (MSA)-matched non-HBCUs (among the top 200 institutions by FY 2021 research expenditures), and FY 2021 research expenditure-matched non-HBCUs.

RESULTS: The authors found that the top 20 HBCUs' mean IDC rates (50.0%) were, after adjustment, 8.5 percentage points (95% confidence interval [CI] 5.7, 11.2) lower than those of the top 40 non-HBCUs (58.5%). The mean IDC rates of top HBCUs (n = 14, 48.4%) were, after adjustment, 6.3 percentage points (95% CI 3.1, 9.4) lower than those of MSA-matched non-HBCUs (n = 23, 55.3%). There was no statistically significant difference in the mean IDC rates between the top 20 HBCUs (50.0%) and expenditure-matched non-HBCUs (n = 31; 48.2%).

CONCLUSIONS: Inequities in negotiated IDC rates between top HBCUs and non-HBCUs likely both reflect and may contribute to the persistence of institution-level inequities in federally funded research. Proactive investments in HBCUs' research infrastructures are likely needed to ameliorate these funding inequities and support the role of HBCUs in providing opportunity for underrepresented groups in biomedical sciences.}, } @article {pmid38525191, year = {2024}, author = {Lopez-Vazquez, P and Fernandez-Caggiano, M and Barge-Caballero, E and Barge-Caballero, G and Couto-Mallon, D and Grille-Cancela, Z and Blanco-Canosa, P and Paniagua-Martin, MJ and Enriquez-Vazquez, D and Vazquez-Rodriguez, JM and Domenech, N and Crespo-Leiro, MG}, title = {Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1349417}, pmid = {38525191}, issn = {2297-055X}, abstract = {INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.

METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.

RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.

CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.}, } @article {pmid38523415, year = {2024}, author = {Seth, A and Slama, EM}, title = {Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348241241736}, doi = {10.1177/00031348241241736}, pmid = {38523415}, issn = {1555-9823}, abstract = {Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.}, } @article {pmid38523303, year = {2024}, author = {Yanase, Y and Bando, H and Sato, R and Matsuo, T and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Hara, H}, title = {Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {150}, pmid = {38523303}, issn = {1752-1947}, abstract = {BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.

CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine.

CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.}, } @article {pmid38517441, year = {2024}, author = {Garza, KY and King, ME and Nagi, C and DeHoog, RJ and Zhang, J and Sans, M and Krieger, A and Feider, CL and Bensussan, AV and Keating, MF and Lin, JQ and Sun, MW and Tibshirani, R and Pirko, C and Brahmbhatt, KA and Al-Fartosi, AR and Thompson, AM and Bonefas, E and Suliburk, J and Carter, SA and Eberlin, LS}, title = {Intraoperative Evaluation of Breast Tissues During Breast Cancer Operations Using the MasSpec Pen.}, journal = {JAMA network open}, volume = {7}, number = {3}, pages = {e242684}, pmid = {38517441}, issn = {2574-3805}, mesh = {Adult ; Female ; Humans ; Middle Aged ; Male ; *Breast Neoplasms/diagnosis/surgery/pathology ; Margins of Excision ; Breast/surgery/pathology ; Mastectomy ; Mass Spectrometry ; }, abstract = {IMPORTANCE: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance.

OBJECTIVE: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information.

In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult patients undergoing breast surgery for ductal carcinomas or nonmalignant conditions. Fresh-frozen tissue samples and touch imprints were analyzed in a laboratory. Intraoperative in vivo and ex vivo breast tissue analyses were performed by surgical staff in operating rooms (ORs) within 2 different hospitals at the Texas Medical Center. Molecular data were used to build statistical classifiers.

MAIN OUTCOMES AND MEASURES: Prediction results of tissue analyses from classification models were compared with gross assessment, frozen section analysis, and/or final postoperative pathology to assess accuracy.

RESULTS: All data acquired from the 143 banked tissue samples, including 79 healthy breast and 64 IDC tissues, were included in the statistical analysis. Data presented rich molecular profiles of healthy and IDC banked tissue samples, with significant changes in relative abundances observed for several metabolic species. Statistical classifiers yielded accuracies of 95.6%, 95.5%, and 90.6% for training, validation, and independent test sets, respectively. A total of 25 participants enrolled in the clinical, intraoperative study; all were female, and the median age was 58 years (IQR, 44-66 years). Intraoperative testing of the technology was successfully performed by surgical staff during 25 breast operations. Of 273 intraoperative analyses performed during 25 surgical cases, 147 analyses from 22 cases were subjected to statistical classification. Testing of the classifiers on 147 intraoperative mass spectra yielded 95.9% agreement with postoperative pathology results.

CONCLUSIONS AND RELEVANCE: The findings of this diagnostic study suggest that the mass spectrometry-based system could be clinically valuable to surgeons and patients by enabling fast molecular-based intraoperative assessment of in vivo and ex vivo breast tissue samples and surgical margins.}, } @article {pmid38512628, year = {2024}, author = {Rescinito, G and Brunetti, N and Garlaschi, A and Tosto, S and Gristina, L and Conti, B and Pieroni, D and Calabrese, M and Tagliafico, AS}, title = {Long-term outcome of 9G MRI-guided vacuum-assisted breast biopsy: results of 293 single-center procedures and underestimation rate of high-risk lesions over 12 years.}, journal = {La Radiologia medica}, volume = {}, number = {}, pages = {}, pmid = {38512628}, issn = {1826-6983}, abstract = {PURPOSE: Breast magnetic resonance imaging (MRI) can detect some malignant lesions that are not visible on mammography (MX) or ultrasound (US). If a targeted, second-look fails, MRI-guided breast biopsy is the only available tool to obtain a tissue sample and pathological proof of these "MRI-only lesions". The aim of this study is to report the performance and underestimation rate of 9G MRI-guided vacuum-assisted breast biopsy (VABB) over 12 years at a single center.

MATERIAL AND METHODS: All 9G MRI-VABB procedures performed from January 2010 to December 2021 were retrospectively reviewed. Two MRI scanners (1.5 T and 3 T) were used with the same image resolution and contrast media. All suspicious lesions detected only by breast MRI underwent biopsy. Reference standard was histological diagnosis or at least 1-year negative follow-up. All malignant and atypical lesions underwent surgery, which was used as the reference standard.

RESULTS: A total of 293 biopsies were retrospectively reviewed. Histopathological VABB results revealed 142/293 (48.4%) benign lesions, 77/293 (26.2%) high-risk lesions, and 74/293 (25.2%) malignant lesions. No significant complications were observed. Surgical pathology results allowed for the reclassification of n = 7/48 B3b lesions: n = 4 were ductal carcinoma in situ, while n = 3 presented invasive features at surgical histology (2 IDC; 1 ILC). B3b underestimation occurred overall in 14.6% of B3 cases. Breast follow-up was achieved for all benign VABB results, and only one false-negative case was observed.

CONCLUSION: Our results confirm that 1.5 T and 3 T MRI-guided VABB is an accurate and safe procedure for histopathologic final diagnosis of MRI-only lesions. Critical issues remain the potential high-risk underestimation rate of B3b VABB results and management of follow-up of benign lesions.}, } @article {pmid38509907, year = {2024}, author = {Yaqing, X and Yang, G and Linlin, Y and Youqing, R and Henghui, Y and Ping, Y and Hongying, Y and Shaojia, W}, title = {Identification of different subtypes of ovarian cancer and construction of prognostic models based on glutamine-metabolism associated genes.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27358}, pmid = {38509907}, issn = {2405-8440}, abstract = {Ovarian cancer (OC) is common malignant tumor of female reproductive system. Glutamine metabolism-related genes (GMRGs) play a key role in ovarian cancer. Here, available database-- The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases were applied in our research. OC samples from TCGA were divided into different clusters based on Cox analysis, which filtering GMRGs with survival information. Then, differentially expressed genes (DEGs) between these clusters were intersected with DEGs between normal ovary samples and OC samples, and GMRGs in order to obtain GMRGs-related DEGs. Next, a risk model of OC was constructed and enrichment analysis of risk model was performed based on hallmark gene set. Besides, the immune cells ratio in OC samples were detected via Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Finally, we explored a series of potential biomarkers of OC. In this research, 9 GMRGs-related DEGs were obtained. GMRGs-related DEGs were enriched to canonical Wnt signaling pathway.NKD2, C2orf88, and KLHDC8A, which were significantly associated with prognosis, were retained for risk model construction. Based on the risk model, 18 hallmark pathways with significant difference were enriched. Fifteen types of immune cells (such as iDC, NK CD56dim cells, and neutrophils) enjoying significant difference between these 2 risk groups (high risk group vs. low risk group) were detected, which indicates possible disparate TME in different metabolic subtypes of ovarian cancer.}, } @article {pmid38507631, year = {2024}, author = {Feizi, I and Isazadehfar, K and Sadegzadeh, F and Farshadi, P}, title = {Histopathological Feature of Early-Onset Breast Cancer: A Comparative Analysis.}, journal = {The international tinnitus journal}, volume = {27}, number = {2}, pages = {167-173}, doi = {10.5935/0946-5448.20230026}, pmid = {38507631}, issn = {0946-5448}, abstract = {BACKGROUND: Breast cancer is one of the most common malignancies among women. In some reports, it has been specified that the diagnosis of breast cancer at an earlier ages worsens the prognosis; this can be attributed to a combination of factors such as advanced stage of disease and late demonstration. Considering different results in last studies, this study's aim was investigation of breast cancer histopathology in two age groups of women under and above 40 years old.

MATERIAL AND METHODS: A cross-sectional study was performed on 64 patients with breast cancer referring to hospitals during 2014 and 2015 years. All histopathologic information is collected from patient's cases. Data were compared in two age groups with equal T. Also, the levels of axillary lymph nodes involvement were evaluated in the equal T for both groups.

RESULTS: We evaluated 64 patients, 71.9% of them were over 40 years old and 28.1% were under 40 years of age. The most common type of tumor was invasive ductal carcinoma. Involvement of the axillary lymph nodes in the equal T was significantly higher in patients less than 40 years of age (p 0.005) than patients over 40 years old (T=1 and T=2) (p=0.032 and p=0.05).

CONCLUSION: Our study signified that in equal T rates the level of axillary lymph nodes involvement in patients younger than 40 years old is higher than those older than 40 years of age. Therefore, breast cancer at early ages is associated with a worse prognosis.}, } @article {pmid38499660, year = {2024}, author = {Seifert, L and Létocart, A and Guignard, B and Regaieg, MA}, title = {Effect of breathing conditions on relationships between impairment, breathing laterality and coordination symmetry in elite para swimmers.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6456}, pmid = {38499660}, issn = {2045-2322}, support = {ANR-19-STHP-0004//Agence Nationale de la Recherche/ ; }, mesh = {Humans ; Biomechanical Phenomena ; *Functional Laterality ; Respiration ; *Musculoskeletal Physiological Phenomena ; Swimming ; Arm ; Vision Disorders ; }, abstract = {The aim was to investigate the effect of breathing conditions and swimming pace on the relationships between the impairment, the breathing laterality and motor coordination symmetry in elite front crawl Para swimmers. Fifteen elite Para swimmers with unilateral physical impairment or with visual impairment and unilateral breathing preference performed eight 25 m using four breathing conditions (every three strokes, every two strokes on preferred and non-preferred breathing side and apnea) at slow and fast paces in a randomized order. Multicamera video system and five sensors have been used to assess arm and leg stroke phases and to compute symmetry of arm coordination (SIIdC) and of leg kick rate (SIKR). Our findings emphasized motor coordination asymmetry whatever the breathing conditions and swimming paces, highlighting the influence of impairment. Multinomial logistic regression exhibited a high probability for motor coordination asymmetry (SIIdC and SIKR) to be present in categories of Para swimmers with impairment and breathing laterality on the same side, suggesting the joined effect of unilateral impairment and unilateral breathing. Moreover, unilateral physical impairment and breathing laterality could also occur on different sides and generate motor coordination asymmetry on different sides and different levels (arms vs. legs). Finally, visual impairment seems amplify the effect of unilateral breathing on motor coordination asymmetry.}, } @article {pmid38497796, year = {2024}, author = {Ward, K and Selvarajah, G and Al-Omishy, H and Sait, M and Khan, HN and McEvoy, K and Robertson, S}, title = {Surgical outcomes of total duct excision in the diagnosis and management of nipple discharge.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {}, number = {}, pages = {}, doi = {10.1308/rcsann.2022.0093}, pmid = {38497796}, issn = {1478-7083}, abstract = {INTRODUCTION: Total duct excision (TDE) is performed for the diagnosis and management of nipple discharge. The Association of Breast Surgery's recent guidelines recommend considering diagnostic surgery for single-duct, blood-stained or clear nipple discharge, and for symptomatic management.

METHODS: We retrospectively reviewed the diagnostic and surgical outcomes of all cases of TDE between January 2013 and November 2019.

RESULTS: In total, 259 TDEs were carried out: 219 for nipple discharge, 29 for recurrent mastitis, 3 for screening abnormalities and 8 for breast lumps. Of the nipple discharge group, 121 had blood-stained discharge. Mean patient age was 52 years (range 19-81). Median follow-up time was 45 months (interquartile range 24-63). The following cases were identified on histopathology: 236 benign breast changes, 10 atypical ductal hyperplasia, 4 lobular carcinoma in situ, 2 low-grade ductal carcinoma in situ (DCIS), 3 intermediate-grade DCIS, 2 high-grade DCIS and 2 invasive ductal carcinomas. In total, 3.5% of patients who underwent TDE had a diagnosis of DCIS or invasive carcinoma. Blood-stained discharge was associated with a significant increase in risk of DCIS or carcinoma compared with other nipple discharge colours (p = 0.043). The most common complications of TDE were infection, poor wound healing and haematoma. Nipple discharge recurred in 14.2% of cases.

CONCLUSIONS: TDE can be considered for the diagnostics and management of nipple discharge. Blood-stained nipple discharge increases the risk of DCIS or malignancy, but the majority of the time TDE reveals benign breast pathology.}, } @article {pmid38485913, year = {2024}, author = {Heidari, N and Abbasi-Kenarsari, H and Niknam, B and Asadirad, A and Amani, D and Mirsanei, Z and Hashemi, SM}, title = {Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {23}, number = {1}, pages = {97-106}, doi = {10.18502/ijaai.v23i1.14957}, pmid = {38485913}, issn = {1735-5249}, mesh = {*Exosomes ; Dendritic Cells ; Bone Marrow ; T-Lymphocytes ; Coculture Techniques ; Cell Differentiation ; }, abstract = {Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.}, } @article {pmid38485644, year = {2024}, author = {Shi, Y and Wang, H and Golijanin, B and Amin, A and Lee, J and Sikov, M and Hyams, E and Pareek, G and Carneiro, BA and Mega, AE and Lagos, GG and Wang, L and Wang, Z and Cheng, L}, title = {Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.01.037}, pmid = {38485644}, issn = {1873-2496}, abstract = {Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.}, } @article {pmid38483129, year = {2024}, author = {Cheng, M and Jia, Z and Zhang, G and Wang, Y and Li, S and Yang, S and Li, C and Geng, C}, title = {Gastric metastasis from breast cancer: five cases and a single-institutional review.}, journal = {The Journal of international medical research}, volume = {52}, number = {3}, pages = {3000605241233988}, doi = {10.1177/03000605241233988}, pmid = {38483129}, issn = {1473-2300}, abstract = {Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.}, } @article {pmid38478781, year = {2023}, author = {VanHoose, L and Eigsti, H}, title = {The Changing Landscape of Intercultural Mindset in 616 Doctor of Physical Therapy Students Over the Past 7 Years and the Implications for Doctor of Physical Therapy Cultural Competence Education.}, journal = {Journal, physical therapy education}, volume = {37}, number = {4}, pages = {271-277}, doi = {10.1097/JTE.0000000000000303}, pmid = {38478781}, issn = {1938-3533}, abstract = {INTRODUCTION: This prospective longitudinal study will report the results of a quantitative analysis of the change in Intercultural Development Inventory (IDI) scores and the distribution of students in 5 orientations along the Intercultural Developmental Continuum (IDC) in 8 cohorts of Doctor of Physical Therapy (DPT) students during their academic preparation.

REVIEW OF LITERATURE: The expanding interest in developing intercultural sensitivity in an increasingly more complex and diverse health care environment calls for the dissemination of research on the effectiveness of innovative curricular models that include psychometrically strong outcome measures. Research suggests that health care providers can develop intercultural sensitivity when provided with didactic knowledge, experiential learning, self-reflection, mentoring, and a systematic individualized development plan.

SUBJECTS: The participants were from a sample of convenience of 616 DPT students from the graduating classes of 2015-2022.

METHODS: The study is a repeated-measure design. The IDI was selected to guide targeted intervention and assessment of intercultural sensitivity at an individual level and group level and was administered in semesters 3 and 8 as part of the DPT program course requirements.

RESULTS: There was significant improvement in the IDI Perceived and Developmental Orientation (DO; P < .001) scores between semesters 3 and 8. There was a significant change (P = .0001) in the distribution of students along the 5 DOs of the IDC with 10% of students regressing 1 orientation, 51.7% of students remaining the same, 33.3% of students advancing 1 orientation, and 5% of students advancing 2 orientations along the IDC. Nearly 40% of participants had a positive shift along the IDC.

DISCUSSION AND CONCLUSION: The results of this study suggest that intercultural sensitivity or mindset, as measured by the IDI, can be developed in DPT students who participate in a targeted intercultural development curriculum based on the Process Model of Cultural Competence by Deardorff and the Developmental Model of Intercultural Sensitivity by Bennett.}, } @article {pmid38476685, year = {2024}, author = {Kohlhase, DR and O'Rourke, JA and Graham, MA}, title = {GmGLU1 and GmRR4 contribute to iron deficiency tolerance in soybean.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1295952}, pmid = {38476685}, issn = {1664-462X}, abstract = {Iron deficiency chlorosis (IDC) is a form of abiotic stress that negatively impacts soybean yield. In a previous study, we demonstrated that the historical IDC quantitative trait locus (QTL) on soybean chromosome Gm03 was composed of four distinct linkage blocks, each containing candidate genes for IDC tolerance. Here, we take advantage of virus-induced gene silencing (VIGS) to validate the function of three high-priority candidate genes, each corresponding to a different linkage block in the Gm03 IDC QTL. We built three single-gene constructs to target GmGLU1 (GLUTAMATE SYNTHASE 1, Glyma.03G128300), GmRR4 (RESPONSE REGULATOR 4, Glyma.03G130000), and GmbHLH38 (beta Helix Loop Helix 38, Glyma.03G130400 and Glyma.03G130600). Given the polygenic nature of the iron stress tolerance trait, we also silenced the genes in combination. We built two constructs targeting GmRR4+GmGLU1 and GmbHLH38+GmGLU1. All constructs were tested on the iron-efficient soybean genotype Clark grown in iron-sufficient conditions. We observed significant decreases in soil plant analysis development (SPAD) measurements using the GmGLU1 construct and both double constructs, with potential additive effects in the GmRR4+GmGLU1 construct. Whole genome expression analyses (RNA-seq) revealed a wide range of affected processes including known iron stress responses, defense and hormone signaling, photosynthesis, and cell wall structure. These findings highlight the importance of GmGLU1 in soybean iron stress responses and provide evidence that IDC is truly a polygenic trait, with multiple genes within the QTL contributing to IDC tolerance. Finally, we conducted BLAST analyses to demonstrate that the Gm03 IDC QTL is syntenic across a broad range of plant species.}, } @article {pmid38471320, year = {2024}, author = {Niu, Q and Li, H and Du, L and Wang, R and Lin, J and Chen, A and Jia, C and Jin, L and Li, F}, title = {Development of a Multi-Parametric ultrasonography nomogram for prediction of invasiveness in ductal carcinoma in situ.}, journal = {European journal of radiology}, volume = {175}, number = {}, pages = {111415}, doi = {10.1016/j.ejrad.2024.111415}, pmid = {38471320}, issn = {1872-7727}, abstract = {OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment.

METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established.

RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867.

CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.}, } @article {pmid38469751, year = {2024}, author = {Abazari, R and Sanati, S and Stelmachowski, P and Wang, Q and Krawczuk, A and Goscianska, J and Liu, M}, title = {Water-Stable Pillared Three-Dimensional Zn-V Bimetal-Organic Framework for Promoted Electrocatalytic Urea Oxidation.}, journal = {Inorganic chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.inorgchem.4c00053}, pmid = {38469751}, issn = {1520-510X}, abstract = {Urea oxidation reaction (UOR) is one of the potential routes in which urea-rich wastewater is used as a source of energy for hydrogen production. Metal-organic frameworks (MOFs) have promising applications in electrocatalytic processes, although there are still challenges in identifying the MOFs' molecular regulation and obtaining practical catalytic systems. The current study sought to synthesize [Zn6(IDC)4(OH)2(Hprz)2]n (Zn-MOF) with three symmetrically independent Zn(II) cations connected via linear N-donor piperazine (Hprz), rigid planar imidazole-4,5-dicarboxylate (IDC[3-]), and -OH ligands, revealing the 3,4T1 topology. The optimized noble-metal-free Zn0.33V0.66-MOF/NF electrocatalysts show higher robustness and performance compared to those of the parent Zn monometallic MOF/NF electrode and other bimetallic MOFs with different Zn-V molar ratios. The low potential of 1.42 V (vs RHE) at 50 mA cm[-2] in 1.0 M KOH with 0.33 M urea required by the developed Zn0.33V0.66-MOF electrode makes its application in the UOR more feasible. The availability of more exposed active sites, ion diffusion path, and higher conductivity result from the distinctive configuration of the synthesized electrocatalyst, which is highly stable and capable of synergistic effects, consequently enhancing the desired reaction. The current research contributes to introducing a practical, cost-effective, and sustainable solution to decompose urea-rich wastewater and produce hydrogen.}, } @article {pmid38468604, year = {2024}, author = {Cappiello, A and Abate, F and Adamo, S and Tepedino, MF and Donisi, L and Ricciardi, C and Avallone, AR and Caterino, M and Cuoco, S and Pellecchia, MT and Amboni, M and Barone, P and Erro, R and Picillo, M}, title = {Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/mds.29774}, pmid = {38468604}, issn = {1531-8257}, abstract = {BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms.

OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP.

METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance.

RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints.

CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.}, } @article {pmid38466719, year = {2024}, author = {Njee, RM and Imeda, CP and Ali, SM and Mushi, AK and Mbata, DD and Kapala, AW and Makundi, EA and Nyigo, VA and Majura, AM and Akyoo, WO and Mbatia, YJ and Baraka, GT and Msovela, JM and Ngadaya, ES and Senkoro, MF and Malebo, HM}, title = {Menstrual health and hygiene knowledge among post menarche adolescent school girls in urban and rural Tanzania.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0284072}, pmid = {38466719}, issn = {1932-6203}, abstract = {Adolescent girls' capacity to lead healthy lives and perform well in school has been hampered by their lack of awareness about menstruation and the requirements for its hygienic management. Lack of enabling infrastructure, improper menstrual supplies, and limited socioeconomic support for good menstrual health and cleanliness are characteristics of schools in Africa South of the Sahara. We evaluated school-age girls' knowledge of menstrual hygiene and identified bottlenecks that could affect policy and programming for menstrual health and hygiene. A school-based cross-sectional study involved 8,012 adolescent school girls in the age group of 11-18 years (mean age = 14.9 years). The study evaluated students' knowledge of menstrual health and hygiene (MHH) from the viewpoints of schools and communities using a combination of qualitative and quantitative approaches. Data was collected using self-administered surveys, focus group discussions, in-depth interviews, and site observations. Girls' older age (AOR = 1.62, P 0.001), having a female guardian (AOR = 1.39: P = 001), and having a parent in a formal job (AOR = 1.03: P 0.023) were positively associated with Menstrual health and Hygiene Knowledge. MHH knowledge levels varied significantly between girls attending government (53.3) and non-government schools (50.5%, P = 0.0001), although they were comparable for girls attending rural and urban schools. Only 21% of the study's schools had at least one instructor who had received training in MHH instruction for students. We have established that the majority of adolescent girls in schools have inadequate knowledge on menstrual health and hygiene, and that school teachers lack the skills to prepare and support young adolescents as they transition into puberty. Concerted actions aimed at building supportive policy are paramount, for school-aged teenagers to learn about and reap the long-term advantages of good menstrual health practices.}, } @article {pmid38461375, year = {2024}, author = {Turhan, Ş and Sultan, DAO and Altuner, EM and Kurnaz, A and Bakır, TK and Altamemi, RAA}, title = {Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.}, journal = {International journal of environmental health research}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09603123.2024.2327530}, pmid = {38461375}, issn = {1369-1619}, abstract = {The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.}, } @article {pmid38455655, year = {2024}, author = {Lorza-Gil, E and Ekim, B and Sancar, G}, title = {Editorial: Organ crosstalk in the pathophysiology and treatment of type-2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1379994}, pmid = {38455655}, issn = {1664-2392}, } @article {pmid38451627, year = {2024}, author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR}, title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e265550}, doi = {10.1590/1519-6984.265550}, pmid = {38451627}, issn = {1678-4375}, mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.}, } @article {pmid38449417, year = {2024}, author = {Yao, S and Goi, T and Takahashi, M and Kono, H and Yokoi, S and Maeda, H}, title = {[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {2}, pages = {214-216}, pmid = {38449417}, issn = {0385-0684}, abstract = {A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.}, } @article {pmid38446859, year = {2024}, author = {Gaeta Gazzola, M and Carmichael, ID and Thompson, E and Beitel, M and Madden, LM and Saeed, G and Hoffman, K and Hammouri, M and Hsaio, C and Barry, DT}, title = {A Quantitative Examination of Illness Models Among People With Opioid Use Disorder Receiving Methadone Treatment.}, journal = {Journal of addiction medicine}, volume = {}, number = {}, pages = {}, pmid = {38446859}, issn = {1935-3227}, abstract = {BACKGROUND: Few studies have examined illness models among people with addiction. We investigated illness models and their associations with demographics and treatment beliefs among patients receiving methadone treatment for opioid use disorder.

METHODS: From January 2019 to February 2020, patients receiving methadone treatment at outpatient opioid treatment programs provided demographics and rated using 1 to 7 Likert-type scales agreement with addiction illness models (brain disease model, chronic medical condition model [CMCM], and no explanation [NEM]) and treatment beliefs. Pairwise comparisons and multivariate regressions were used to examine associations between illness models, demographics, and treatment beliefs. Statistical significance was set at P < 0.05.

RESULTS: A total of 450 patients participated in the study. Forty percent self-identified as female, 13% as Hispanic, and 78% as White; mean age was 38.5 years. Brain disease model was the most frequently endorsed illness model (46.2%), followed by CMCM (41.7%) and NEM (21.9%). In multivariate analyses, agreement with brain disease model was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, and methadone is lifesaving, whereas agreement with CMCM was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, 12-step is the best treatment, taking methadone daily is important, and methadone is lifesaving. In multivariate analyses, agreement with NEM was negatively significantly associated with beliefs that methadone would be effective, counseling is important, taking methadone daily is important, and methadone is lifesaving.

DISCUSSION: Many patients in methadone treatment endorsed medicalized addiction models. Agreement with addiction illness models appear to be related to treatment beliefs.}, } @article {pmid38439896, year = {2024}, author = {Hu, J and Shen, Y and Zhang, K and Chen, Y}, title = {Germline RECQL gene mutations in Chinese patients with breast cancer.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1366769}, pmid = {38439896}, issn = {2296-858X}, abstract = {INTRODUCTION: Breast cancer is the most common malignant tumor in women, seriously threatening health and survival. TP-dependent DNA helicase Q1 (RECQL) is a breast cancer susceptibility gene with possible familial links. However, RECQL gene mutations among Chinese women with breast cancer have not been evaluated. Therefore, this study assessed RECQL mutations and their relationships with clinicopathological and epidemiological characteristics in Chinese women with breast cancer.

METHOD: Clinical information was also obtained via the hospital information system and a follow-up questionnaire. Peripheral venous blood (2 mL) was extracted from all patients and stored at -80°C for future use; the early venous blood samples were from our hospital's sample bank. RECQL gene sequencing were performed by the Shanghai Aishe Gene Company (China).

RESULTS: We found that a RECQL mutation is a susceptibility factor for breast cancer. Moreover, patients with RECQL mutations were more likely to have a family history of breast cancer than those without. Also, patients with RECQL variants of uncertain significance (VUS) were less likely to develop invasive ductal carcinoma than those without. In addition, unexplained RECQL mutations occurred more often in patients with human epidermal growth factor receptor 2+ breast cancer than in those with other subtypes.

DISCUSSION: These results provide a basis for creating screening criteria specific to Chinese women. However, the frequency of RECQL mutations was low, and the number of pathogenic mutations was too small and could not be analyzed. Thus, more extensive, long-term studies that include other functional experiments are needed to verify these results.}, } @article {pmid38438841, year = {2024}, author = {Molière, S and Lodi, M and Leblanc, S and Gressel, A and Mathelin, C and Alpy, F and Chenard, MP and Tomasetto, C}, title = {MMP-11 expression in early luminal breast cancer: associations with clinical, MRI, pathological characteristics, and disease-free survival.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {295}, pmid = {38438841}, issn = {1471-2407}, support = {ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-10-IDEX-0002//IdEx Unistra/ ; ANR-17-EURE-0023//EUR IMCBio/ ; ANR-17-EURE-0023//EUR IMCBio/ ; ANR-17-EURE-0023//EUR IMCBio/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; Ligue Contre le Cancer//Ligue Contre le Cancer/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; SEVE (Sein et Vie)//SEVE (Sein et Vie)/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; Alsace Contre le Cancer//Alsace Contre le Cancer/ ; }, abstract = {BACKGROUND: Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers.

METHODS: In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed.

RESULTS: Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11.

CONCLUSION: MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.}, } @article {pmid38438204, year = {2024}, author = {Omer, AA and Bin Dayel, SA and Hummedi, AS and Almuhaimed, NI}, title = {The epidemiological and clinicopathological features of breast cancer in Riyadh, Saudi Arabia.}, journal = {Saudi medical journal}, volume = {45}, number = {3}, pages = {288-294}, doi = {10.15537/smj.2024.45.3.20230656}, pmid = {38438204}, issn = {1658-3175}, abstract = {OBJECTIVES: To investigate the epidemiological and clinicopathological features of breast cancer (BC) in Saudi Arabia to improve decisions regarding resource allocation, disease control, and management.

METHODS: We retrieved the records of all patients who presented with histologically proven BC at King Fahad Medical City between 2019 and 2020. The data were analyzed quantitatively, and the results were expressed as percentages and frequencies.

RESULTS: This study comprised 419 patients. The mean age was 50.13 (± 10.96) years. The majority of the patients were obese (56.6%), and approximately a quarter had a history of oral contraceptive pill use, breast biopsy, or an affected family member. Most cases were from the central region (80.1%), followed by the southern provinces (12.7%). Breast lumps were the most common complaint (89%), whereas hypertension and diabetes mellitus were the most common comorbidities. Invasive ductal carcinoma was the most common pathologic type (89.7%). Most patients presented with TNM stages II and III (55.2%), and 27.7% had metastasis. The main therapeutic modalities included radical mastectomy (63.8%), neoadjuvant chemotherapy (60.4%), and adjuvant radiotherapy (82.9%).

CONCLUSION: In Saudi Arabia, a trend of BC incidence migration towards older patients may be ensuing. However, prediction of an advanced and aggressive presentation requires the enhancement of screening programs and standardized protocols for disease management.}, } @article {pmid38437141, year = {2024}, author = {Hall, G and Liang, W and Bhujwalla, ZM and Li, X}, title = {SHG fiberscopy assessment of collagen morphology and its potential for breast cancer optical histology.}, journal = {IEEE transactions on bio-medical engineering}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TBME.2024.3372629}, pmid = {38437141}, issn = {1558-2531}, abstract = {OBJECTIVE: this study is to investigate the feasibility of our recently developed nonlinear fiberscope for label-free in situ breast tumor detection and lymph node status assessment based on second harmonic generation (SHG) imaging of fibrillar collagen matrix with histological details. The long-term goal is to improve the current biopsy-based cancer paradigm with reduced sampling errors.

METHODS: in this pilot study we undertook retrospective SHG imaging study of ex vivo invasive ductal carcinoma human biopsy tissue samples, and carried out quantitative image analysis to search for collagen structural signatures that are associated with the malignance of breast cancer.

RESULTS: SHG fiberscopy image-based quantitative assessment of collagen fiber morphology reveals that: 1) cancerous tissues contain generally less extracellular collagen fibers compared with tumor-adjacent normal tissues, and 2) collagen fibers in lymph node positive biopsies are more aligned than lymph node negative counterparts.

CONCLUSION/SIGNIFICANCE: the results demonstrate the promising potential of our SHG fiberscope for in situ breast tumor detection and lymph node involvement assessment and for offering real-time guidance during ongoing tissue biopsy.}, } @article {pmid38433052, year = {2024}, author = {Sun, Q and Sun, JJ and Wang, M and Zhang, L and Zhang, XW and Wei, JG and Kong, LF and Li, J}, title = {[Intraductal carcinomas of the salivary glands: a clinicopathological and molecular genetic analysis of twenty-seven cases].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {53}, number = {3}, pages = {250-256}, doi = {10.3760/cma.j.cn112151-20230808-00056}, pmid = {38433052}, issn = {0529-5807}, support = {YBKB202106//Establishment of a Biobank for Head and Neck Cancer Based on Heterogeneity of Invasion and Metastasis of Shanghai Ninth People's Hospital/ ; }, abstract = {Objective: To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands. Methods: Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People's Hospital and two cases from Department of Pathology, Henan Provincial People's Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed. Results: There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption. Conclusions: IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.}, } @article {pmid38432595, year = {2024}, author = {Chuang, ML}, title = {Analyzing Key Elements of Breathing Patterns, Deriving Remaining Variables, and Identifying Cutoff Values in Individuals with Chronic Respiratory Disease and Healthy Subjects.}, journal = {Respiratory physiology & neurobiology}, volume = {}, number = {}, pages = {104242}, doi = {10.1016/j.resp.2024.104242}, pmid = {38432595}, issn = {1878-1519}, abstract = {BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.

METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.

RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104L/min may differentiate ILD from control, while V̇E of 54L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99s, and IDC of.45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).

CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.}, } @article {pmid38432310, year = {2024}, author = {Gimeno-Morales, M and Martínez-Monge, R and Martinez-Lage, A and Jablonska, PA and Blanco, J and Martínez-Regueira, F and Rodriguez-Spiteri, N and Olartecoechea, B and Ramos, L and Insausti, LP and Elizalde, A and Abengozar, M and Cambeiro, M}, title = {Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {}, number = {}, pages = {110193}, doi = {10.1016/j.radonc.2024.110193}, pmid = {38432310}, issn = {1879-0887}, abstract = {BACKGROUND AND PURPOSE: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation(APBI) in early breast cancer patients. Intraoperative multicatheter breast implant(IOMBI) followed by perioperative high-dose-rate brachytherapy(PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution.

MATERIALS AND METHODS: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT.

RESULTS: A total of 171 patients underwent IOMBI during BCS, 120 patients(70.1 %) were suitable for APBI and 51(29.8 %) for anticipated PHDRBT-boost. The median age was 61 years(range: 40-78), the median tumor size was 1.1 cm(range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range:4-14) were used. For APBI, the median CTV and V100 were 40.8 cc (range:8.6-99) and 35.4 cc (range:7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range:2.3-28 %) and the median local treatment duration was 10 days (range:7-16). With a median follow-up of 8.8 years (range:0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %.

CONCLUSION: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.}, } @article {pmid38424901, year = {2020}, author = {Samreen, N and Moy, L and Lee, CS}, title = {Architectural Distortion on Digital Breast Tomosynthesis: Management Algorithm and Pathological Outcome.}, journal = {Journal of breast imaging}, volume = {2}, number = {5}, pages = {424-435}, doi = {10.1093/jbi/wbaa034}, pmid = {38424901}, issn = {2631-6129}, abstract = {Architectural distortion on digital breast tomosynthesis (DBT) can occur due to benign and malignant causes. With DBT, there is an increase in the detection of architectural distortion compared with 2D digital mammography, and the positive predictive value is high enough to justify tissue sampling when imaging findings are confirmed. Workup involves supplemental DBT views and ultrasound, with subsequent image-guided percutaneous biopsy using the modality on which it is best visualized. If architectural distortion is subtle and/or questionable on diagnostic imaging, MRI may be performed for problem solving, with subsequent biopsy of suspicious findings using MRI or DBT guidance, respectively. If no suspicious findings are noted on MRI, a six-month follow-up DBT may be performed. On pathology, malignant cases are noted in 6.8%-50.7% of the cases, most commonly due to invasive ductal carcinoma, followed by invasive lobular carcinoma. Radial scars are the most common benign cause, with stromal fibrosis and sclerosing adenosis being much less common. As there is an increase in the number of benign pathological outcomes for architectural distortion on DBT compared with 2D digital mammography, concordance should be based on the level of suspicion of imaging findings. As discordant cases have upgrade rates of up to 25%, surgical consultation is recommended for discordant radiologic-pathologic findings.}, } @article {pmid38419665, year = {2024}, author = {Liao, YC and Yang, CJ and Yu, HY and Huang, CJ and Hong, TY and Li, WC and Chen, LF and Hsieh, JC}, title = {Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1342326}, pmid = {38419665}, issn = {1662-4548}, abstract = {INTRODUCTION: The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP).

METHODS: The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions.

RESULTS: Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule.

DISCUSSION: PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.}, } @article {pmid38424859, year = {2020}, author = {Bonnet, SE and Carter, GJ and Berg, WA}, title = {Encapsulated Papillary Carcinoma of the Breast: Imaging Features with Histopathologic Correlation.}, journal = {Journal of breast imaging}, volume = {2}, number = {6}, pages = {590-597}, doi = {10.1093/jbi/wbaa068}, pmid = {38424859}, issn = {2631-6129}, abstract = {Encapsulated papillary carcinoma (EPC) is a rare, clinically indolent breast malignancy most common in postmenopausal women. Absence of myoepithelial cells at the periphery is a characteristic feature. Mammographically, EPC typically presents as a mostly circumscribed, noncalcified, dense mass that can have focally indistinct margins when there is associated frank invasive carcinoma. Ultrasound shows a circumscribed solid or complex cystic and solid mass, and occasional hemorrhage in the cystic component may produce a fluid-debris level; the solid components typically show intense washout enhancement on MRI. Color Doppler may demonstrate a prominent vascular pedicle and blood flow within solid papillary fronds. Encapsulated papillary carcinoma can exist in pure form; however, EPC is often associated with conventional ductal carcinoma in-situ and/or invasive ductal carcinoma, no special type. Adjacent in-situ and invasive disease may be only focally present at the periphery of EPC and potentially unsampled at core-needle biopsy. In order to facilitate diagnosis, the mass wall should be included on core-needle biopsy, which will show absence of myoepithelial markers. Staging and prognosis are determined by any associated frankly invasive component, with usually excellent long-term survival and rare distant metastases.}, } @article {pmid38424856, year = {2020}, author = {Chen, C and Dodelzon, K and Ginter, PS and Drotman, MB and Arleo, EK}, title = {Postoperative Imaging Appearance of an Implantable Three-dimensional Bioabsorbable Tissue Marker After Breast Surgery: Initial Experience at a Single Institution.}, journal = {Journal of breast imaging}, volume = {2}, number = {6}, pages = {561-568}, doi = {10.1093/jbi/wbaa081}, pmid = {38424856}, issn = {2631-6129}, abstract = {OBJECTIVE: Three-dimensional bioabsorbable tissue marker (BTM) placement during breast surgery is performed for the purpose of improved surgical cavity delineation for radiotherapy and improved cosmetic outcome. The purpose of this study is to evaluate the postsurgical imaging findings of BTM.

METHODS: This Institutional Review Board-approved retrospective review included all patients implanted with BTM at breast surgery from January 2017 to September 2018. Demographics, tumor characteristics, imaging, and histologic findings were evaluated. Medical records were reviewed during a three-year period to evaluate for tumor recurrence.

RESULTS: Ninety-seven patients had BTM implanted, of which 76 patients had imaging follow-up of at least 1 year. Of the 76 patients who had mammographic follow-up, 3 (3.9%) developed suspicious microcalcifications requiring biopsy, yielding ductal carcinoma in-situ in 2 patients and benign calcifications in 1 patient. Of 61 patients who had sonographic follow-up, 44 (72.1%) patients had complex fluid collections containing avascular, heterogeneously hyperechoic solid components, which remained stable or decreased in size over time; no recurrent tumors were found in this group. One patient (1.6%) had a vascular solid mass, which yielded recurrent papilloma. Four (6.6%) patients developed irregular hypoechoic masses at the surgical site, one of which corresponded with a developing asymmetry mammographically; biopsy yielded fibromatosis. Tissue sampling of the remaining three cases yielded invasive ductal carcinoma, fat necrosis, and radiation changes, respectively.

CONCLUSION: Accurate identification of the expected postoperative imaging appearance of BTM may prevent unnecessary biopsy. Suspicious findings necessitating biopsy are pleomorphic calcifications, developing asymmetry and vascular and irregular hypoechoic masses.}, } @article {pmid38424872, year = {2019}, author = {Grimm, LJ and Enslow, M and Ghate, SV}, title = {Solitary, Well-Circumscribed, T2 Hyperintense Masses on MRI Have Very Low Malignancy Rates.}, journal = {Journal of breast imaging}, volume = {1}, number = {1}, pages = {37-42}, doi = {10.1093/jbi/wby014}, pmid = {38424872}, issn = {2631-6129}, abstract = {OBJECTIVE: The purpose of this study was to determine the malignancy rate of solitary MRI masses with benign BI-RADS descriptors.

METHODS: A retrospective review was conducted of all breast MRI reports that described a mass with a final BI-RADS assessment of 3, 4, or 5, from February 1, 2005, through February 28, 2014 (n = 1510). Studies were excluded if the mass was not solitary, did not meet formal criteria for a mass, or had classically suspicious BI-RADS features (e.g., washout kinetics, and spiculated margin). The masses were reviewed by 2 fellowship-trained breast radiologists who reported consensus BI-RADS mass margin, shape, internal-enhancement, and kinetics descriptors. The T2 signal was reported as hyperintense if equal to or greater than the signal intensity of the axillary lymph nodes. Pathology results or 2 years of imaging follow-up were recorded. Comparisons were made between mass descriptors and clinical outcomes.

RESULTS: There were 127 women with 127 masses available for analysis. There were 76 (60%) masses that underwent biopsy for an overall malignancy rate of 4% (5/127): 2 ductal carcinoma in situ (DCIS) and 3 invasive ductal carcinoma. The malignancy rate was 2% (1/59) for T2 hyperintense solitary masses. The malignancy rate was greater than 2% for all of the following BI-RADS descriptors: oval (3%, 3/88), round (5%, 2/39), circumscribed (4%, 5/127), homogeneous (4%, 3/74), and dark internal septations (4%, 2/44).

CONCLUSION: T2 hyperintense solitary masses without associated suspicious features have a low malignancy rate, and they could be considered for a BI-RADS 3 final assessment.}, } @article {pmid38419320, year = {2024}, author = {Toshima, K and Shien, T and Nishimura, MF and Suzuki, Y and Nakamoto, S and Uno, M and Yoshioka, R and Tsukioki, T and Takahashi, Y and Iwamoto, T and Iwatani, T and Yanai, H}, title = {Ectopic Breast Cancer Arising within an Axillary Lymph Node.}, journal = {Acta medica Okayama}, volume = {78}, number = {1}, pages = {89-93}, doi = {10.18926/AMO/66676}, pmid = {38419320}, issn = {0386-300X}, abstract = {We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis.}, } @article {pmid38417222, year = {2024}, author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B}, title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.}, journal = {Neoplasia (New York, N.Y.)}, volume = {50}, number = {}, pages = {100983}, doi = {10.1016/j.neo.2024.100983}, pmid = {38417222}, issn = {1476-5586}, abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.}, } @article {pmid38416903, year = {2023}, author = {Miceli, R and Mercado, CL and Hernandez, O and Chhor, C}, title = {Active Surveillance for Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ.}, journal = {Journal of breast imaging}, volume = {5}, number = {4}, pages = {396-415}, doi = {10.1093/jbi/wbad026}, pmid = {38416903}, issn = {2631-6129}, abstract = {Atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are relatively common breast lesions on the same spectrum of disease. Atypical ductal hyperblasia is a nonmalignant, high-risk lesion, and DCIS is a noninvasive malignancy. While a benefit of screening mammography is early cancer detection, it also leads to increased biopsy diagnosis of noninvasive lesions. Previously, treatment guidelines for both entities included surgical excision because of the risk of upgrade to invasive cancer after surgery and risk of progression to invasive cancer for DCIS. However, this universal management approach is not optimal for all patients because most lesions are not upgraded after surgery. Furthermore, some DCIS lesions do not progress to clinically significant invasive cancer. Overtreatment of high-risk lesions and DCIS is considered a burden on patients and clinicians and is a strain on the health care system. Extensive research has identified many potential histologic, clinical, and imaging factors that may predict ADH and DCIS upgrade and thereby help clinicians select which patients should undergo surgery and which may be appropriate for active surveillance (AS) with imaging. Additionally, multiple clinical trials are currently underway to evaluate whether AS for DCIS is feasible for a select group of patients. Recent advances in MRI, artificial intelligence, and molecular markers may also have an important role to play in stratifying patients and delineating best management guidelines. This review article discusses the available evidence regarding the feasibility and limitations of AS for ADH and DCIS, as well as recent advances in patient risk stratification.}, } @article {pmid38416170, year = {2024}, author = {Maggi, G and Loayza, F and Vitale, C and Santangelo, G and Obeso, I}, title = {Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.}, journal = {Journal of neurology}, volume = {}, number = {}, pages = {}, pmid = {38416170}, issn = {1432-1459}, abstract = {BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD).

OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD.

METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning.

RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions.

CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.}, } @article {pmid38414161, year = {2024}, author = {Geppert, J and Rohm, M}, title = {Cancer cachexia: biomarkers and the influence of age.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13590}, pmid = {38414161}, issn = {1878-0261}, support = {//Helmholtz-Gemeinschaft/ ; 949017//European Commission/ ; }, abstract = {Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.}, } @article {pmid38410339, year = {2024}, author = {Al Husban, H and Al Rabadi, A and Odeh, AH and Abu Rumman, K and Alkhawaldeh, F and Noures, H and Abo Ashoor, M and Abu Rumman, A and Atmeh, M and Bawaneh, M}, title = {Clinical Characteristics and Management of Triple-Negative Breast Cancer (TNBC) in Jordan: A Retrospective Analysis.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e53053}, pmid = {38410339}, issn = {2168-8184}, abstract = {Introduction Triple-negative breast cancer (TNBC) is known for its aggressive nature and poor prognosis. Despite its responsiveness to chemotherapy, TNBC presents challenges in terms of survival, recurrence, and mortality rates, particularly in diverse populations. Limited research in the Middle East hampers comprehensive understanding and tailored management. Methods A retrospective study at the King Hussein Medical Center in Jordan between the period 2009 to 2023 explored TNBC patients (n=110) who underwent adjuvant chemotherapy after local excision or modified radical mastectomy (MRM). Data encompassed demographics, clinical variables, and operative details. Statistical analysis employed Wilcoxon and chi-squared tests, examining mortality risks and associations between variables. Results Among 110 TNBC patients (mean age 52), 84% underwent MRM, 16% wide local excision and axillary clearance (WLE&AC). Lymphovascular invasion (LVI) was observed in 41%, linked to higher lymph node positivity. Neoadjuvant therapy preceded MRM in 25% of cases. While 75% had grade III tumors, the prevalence of invasive ductal carcinoma was 85%. Conclusions This study contributes crucial insights into TNBC characteristics and management in Jordan. Despite limitations such as retrospective design and sample size, the findings underscore the need for tailored interventions in TNBC patients, emphasizing the importance of neoadjuvant therapy and vigilant consideration of LVI status in treatment planning. Future longitudinal research should delve into disease progression and treatment outcomes in diverse populations, facilitating optimized TNBC management strategies.}, } @article {pmid38410238, year = {2024}, author = {Chen, Y and Xu, Z and Chen, Y and Dai, Y and Ding, J}, title = {Comparison of the prognosis of medullary breast carcinoma and invasive ductal carcinoma: a SEER-based study.}, journal = {Translational cancer research}, volume = {13}, number = {1}, pages = {231-248}, pmid = {38410238}, issn = {2219-6803}, abstract = {BACKGROUND: Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients.

METHODS: A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy.

RESULTS: There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors.

CONCLUSIONS: MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.}, } @article {pmid38409747, year = {2024}, author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , }, title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.}, journal = {American journal of hematology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajh.27263}, pmid = {38409747}, issn = {1096-8652}, support = {CA97422//University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE)/ ; }, abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.}, } @article {pmid38409268, year = {2024}, author = {Alkhafaji, S and Wolf, DM and Magbanua, MJM and J van 't Veer, L and Park, JW and Esserman, L and Mukhtar, RA}, title = {Circulating tumor cells in early lobular versus ductal breast cancer and their associations with prognosis.}, journal = {NPJ breast cancer}, volume = {10}, number = {1}, pages = {17}, pmid = {38409268}, issn = {2374-4677}, support = {K08CA256047//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {This is a secondary data analysis of the TIPPING study, which included 1,121 patients with stage I-III breast cancer who had enumeration of CTCs (by either CellSearch or immunomagnetic enrichment and flow cytometry [IE/FC]) and disseminated tumor cells (DTCs) at the time of surgical resection between 1999 and 2012. The primary endpoint was mean number of CTCs by histology, taking into account method of detection and treatment type, and evaluation of histology specific prognostic cutpoints. Overall, patients with ILC had significantly higher CTC counts than those with IDC, a finding which persisted in the 382 patients with CTC enumeration by IE/FC method. Additionally, among those with primary surgery, patients with ILC had significantly higher mean CTC counts than those with IDC (mean 2.11 CTCs/mL versus 0.71 CTCs/mL respectively, p < 0.001), which persisted on multivariate analysis. Patients with ILC and CTC-high/DTC-high status trended towards reduced DRFS HR = 9.27, 95% CI 0.95-90.5, p = 0.055) and had significantly decreased BCSS (HR = 10.4, 95% CI 1.07-99.7, P = 0.043) compared with those who were CTC-low/DTC-low. In the IDC group, CTC-high/DTC-high status was not associated with either DRFS or BCSS. In neoadjvuantly treated patients, there was no significant difference in CTC counts in the ILC group versus the IDC group (mean 0.89 CTCs/mL versus 1.06 CTCs/mL respectively, p = 0.82). Our findings contribute to the limited literature on CTCs and DTCs in ILC, and suggest that clinical utility and optimal thresholds for CTC and DTC assays may differ by histologic subtype in early-stage breast cancer.}, } @article {pmid38406950, year = {2023}, author = {Asad, S and Khan, SA and Khan, FA and Jalal-Ud-Din, M and Bhatti, G and Kamran, H}, title = {Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35}, number = {4}, pages = {629-632}, doi = {10.55519/JAMC-04-12089}, pmid = {38406950}, issn = {1819-2718}, abstract = {BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.

METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.

RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.

CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.}, } @article {pmid38406898, year = {2023}, author = {, and Haider, G and Shaikh, Z and Memon, P and Shahid, A and Rahul, R and Kumar, P and Beg, S and Parkash, J}, title = {Significance of ca15-3 in carcinoma of the breast with Visceral metastases.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35(Suppl 1)}, number = {4}, pages = {S710-S714}, pmid = {38406898}, issn = {1819-2718}, abstract = {BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.

METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.

RESULTS: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).

CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.}, } @article {pmid38406616, year = {2023}, author = {Netea, PDMG}, title = {I. IDC Key-note Lecture: Trained immunity: a memory for innate host defense.}, journal = {Journal of stem cells & regenerative medicine}, volume = {19}, number = {2}, pages = {37-39}, pmid = {38406616}, issn = {0973-7154}, } @article {pmid38406064, year = {2024}, author = {Udquim, KT and Lam, NB and Altshuler, E and Lin, RY}, title = {Primary Invasive Ductal Carcinoma of the Breast Occurring in a Patient With a History of Hepatocellular Carcinoma Developing From Focal Nodular Hyperplasia: A Case Report and Literature Review.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52818}, pmid = {38406064}, issn = {2168-8184}, abstract = {The risk of developing another primary malignancy after an initial liver cancer diagnosis is rare, and the management of multiple primary cancers is not typically discussed. Focal nodular hyperplasia (FNH) is considered a benign tumor, but there have been cases reported that describe hepatocellular carcinoma (HCC) arising from or within FNH. Here, we report a woman in her 70s who had a longstanding history of FNH, later found to be HCC upon resection, who also developed invasive ductal carcinoma. She had no family history of cancer and no genetic testing results were available. Each of her cancers was managed independently, hepatectomy for HCC and neoadjuvant therapy followed by mastectomy for her breast carcinoma. This case demonstrates that the diagnosis of FNH based on radiographic imaging may necessitate a biopsy to confirm diagnosis for a symptomatic patient or those with lesions suspicious for malignancy. It also showcases the importance of close follow-up after a primary cancer diagnosis for the possibility of another primary malignancy emerging. Fresh tissue biopsy for new lesions could help determine primary malignancy or metastasis. Genetic sequencing may help identify driver mutations or genetic alterations that can be targeted.}, } @article {pmid38405107, year = {2024}, author = {Bhimani, F and Lin, S and McEvoy, M and Cavalli, A and Obaid, L and Chen, Y and Gupta, A and Pastoriza, J and Shihabi, A and Feldman, S}, title = {Does Nipple-Ward Positive Margin Contribute to a Higher Rate of Re-Excision Procedures After a Lumpectomy with Pathology-Confirmed Positive Margins? A Retrospective Study.}, journal = {Breast cancer (Dove Medical Press)}, volume = {16}, number = {}, pages = {41-50}, pmid = {38405107}, issn = {1179-1314}, abstract = {BACKGROUND: Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population.

METHODS:  A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate.

RESULTS: A total of 98 patients' data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases.

CONCLUSION: Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.}, } @article {pmid38404556, year = {2024}, author = {Munien, K and Ravichandran, K and Flynn, H and Shugg, N and Flynn, D and Chambers, J and Desai, D}, title = {Catheter-associated meatal pressure injuries (CAMPI) in patients with long-term urethral catheters-a cross-sectional study of 200 patients.}, journal = {Translational andrology and urology}, volume = {13}, number = {1}, pages = {42-52}, pmid = {38404556}, issn = {2223-4691}, abstract = {BACKGROUND: Indwelling urethral catheters (IDC) are ubiquitous to healthcare settings, and are associated with many familiar risks like haematuria, infections, bladder spasms and stones. However, a less known complication is catheter-associated meatal pressure injury (CAMPI), especially in those with long-term IDCs. The objective of this study was to explore the prevalence, associated features and management of CAMPI in adults with a long-term IDC.

METHODS: A cross-sectional multi-centre study was undertaken of 200 adults with a long-term IDC across regional south-west Queensland, Australia between June 2019 to June 2021. The prevalence of CAMPI was determined by clinical examination, voluntary surveys completed by participants and documentation in medical records. Key IDC statistics included total duration of IDC, location of IDC changes, IDC size, type and fixation.

RESULTS: Out of 200 adults with a long-term IDC, 9% (18/200) had a CAMPI. There was a higher prevalence of male CAMPI (17/169, 10%) compared to female CAMPI (1/31, 3%). The median time to identification of a CAMPI after initial IDC insertion was 12 weeks (2-136 weeks), but occurred as soon as 2 weeks. CAMPI formation was associated with IDC changes in the community, impaired mobility and congestive cardiac failure (CCF). CAMPI were mostly treated by conservative means given the frailty of the population.

CONCLUSIONS: Poor mobility, community-managed IDCs, and CCF were all found to have statistically significant associations with the development of CAMPI. CAMPI represents an important and underserved iatrogenic complication within urology practice, and greater awareness is needed to prevent it in vulnerable patients with long-term IDCs.}, } @article {pmid38404027, year = {2024}, author = {Greenblatt-Kimron, L and Palgi, Y and Regev, T and Ben-David, BM}, title = {Associations among loneliness, internal locus of control and subjective accelerated ageing in older adults who received the booster vaccination.}, journal = {BJPsych open}, volume = {10}, number = {2}, pages = {e54}, doi = {10.1192/bjo.2024.14}, pmid = {38404027}, issn = {2056-4724}, abstract = {BACKGROUND: A rise in loneliness among older adults since the COVID-19 outbreak, even after vaccination, has been highlighted. Loneliness has deleterious consequences, with specific effects on perceptions of the ageing process during the COVID-19 pandemic. Coping with stressful life events and the challenges of ageing may result in a perception of acceleration of this process.

AIM: Studies have shown a buffering effect of an internal locus of control in the relationship between COVID-19 stress and mental distress. The current study examined whether loneliness predicts subjective accelerated ageing and whether internal locus of control moderates this relationship.

METHOD: Two waves of community-dwelling older adults (M = 70.44, s.d. = 5.95; age range 61-88 years), vaccinated three times, were sampled by a web-survey company. Participants completed the questionnaire after the beginning of the third vaccination campaign and reported again 4 months later on loneliness, internal locus of control and subjective accelerated ageing level in the second wave.

RESULTS: Participants with higher levels of loneliness presented 4 months later with higher subjective accelerated ageing. Participants with a low level of internal locus of control presented 4 months later with high subjective accelerated ageing, regardless of their loneliness level. Participants with a high level of internal locus of control and a low level of loneliness presented with the lowest subjective accelerated ageing 4 months later.

CONCLUSIONS: The findings emphasise the deleterious effects of loneliness and low internal locus of control on older adults' perception of their ageing process. Practitioners should focus their interventions not only on loneliness but also on improving the sense of internal locus of control to improve subjective accelerated ageing.}, } @article {pmid38402816, year = {2024}, author = {Laroiya, I and Tan, M and Kaehne, A and Shetty, G}, title = {A prospective study evaluating patient reported outcome measures in patients who have undergone chest wall perforator flaps.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {91}, number = {}, pages = {79-82}, doi = {10.1016/j.bjps.2024.02.044}, pmid = {38402816}, issn = {1878-0539}, abstract = {AIMS: To evaluate Patient Reported Outcome Measures (PROMs) and surgical outcomes in patients undergoing Chest Wall Perforator Flaps (CWPFs).

METHODS: This was an observational single cohort study using an audit approach and a survey instrument. 84 patients who had undergone CWPFs in the last 5 years at the Department of Breast Surgery, City Hospital Birmingham, were identified from a pre-existing database. Surgical outcomes were recorded. Patients were contacted telephonically or in person at the time of follow-up and were asked to fill up a PROMs questionnaire.

RESULTS: Out of 84 patients, 58 patients chose to respond. The average age of the patients was 51.3 years (±8.2 years). The average follow-up was 15.4 months (±9.9 months). The most common histological subtype was Infiltrating ductal carcinoma (IDC)-Not otherwise specified 34/58 (58.6%). Majority of the patients had T2 cancers-28/58 (48.3%). 26/58 (44.8%) were node negative. Eight patients (13.7%) had post-operative complications. No patient had total/partial flap loss. Nine patients (15.5%) had margin re-excision. One patient developed distant metastasis while 1 patient developed a second primary. Fifty-one patients (88%) were either satisfied or very satisfied with the post-operative appearance of the breasts. Thirty-six patients (62%) had no/little persistent pain or tenderness post-surgery. Eighty-six per cent (38/44) of the patients undergoing Lateral Intercostal Artery Perforator (LICAP) Flap and 16/18 (89%) of patients undergoing Anterior Intercostal Artery Perforator (AICAP) flap had no/little difficulty in carrying out normal activities at follow up.

CONCLUSION: CWPFs are associated with a low complication rate and a high patient satisfaction rate.}, } @article {pmid38399000, year = {2024}, author = {Khan, MRR}, title = {Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.}, journal = {Micromachines}, volume = {15}, number = {2}, pages = {}, pmid = {38399000}, issn = {2072-666X}, abstract = {In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.}, } @article {pmid38396137, year = {2024}, author = {Matsumoto, T and Tanaka, G and Mori, S and Niki, M and Sato, S and Shiraki, T and Iso, Y and Nagashima, K and Irisawa, A and Nozawa, Y and Takada-Owada, A and Ishida, K and Aoki, T}, title = {A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.}, journal = {Clinical journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {38396137}, issn = {1865-7265}, abstract = {A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.}, } @article {pmid38393931, year = {2024}, author = {Yang, XL and Ni, DH and Yu, Y and Zhao, JC and Lin, R and Xiu, C and Chang, ZX}, title = {Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {}, number = {}, pages = {}, doi = {10.3233/THC-230671}, pmid = {38393931}, issn = {1878-7401}, abstract = {BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy.

METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated.

RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model.

CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.}, } @article {pmid38388422, year = {2024}, author = {Gan, J and Liu, M and Liu, F and Wen, J and Fu, W and Jia, J}, title = {Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {93}, pmid = {38388422}, issn = {1471-2466}, abstract = {BACKGROUND: Although lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature.

CASE PRESENTATION: A 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient's diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20).

CONCLUSIONS: To the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.}, } @article {pmid38380465, year = {2024}, author = {Anichkina, KA and Pasternak, AV and Arslanov, KS and Kvetenadze, GE and Shivilov, EV and Klimashevich, AV}, title = {[Domestic system for fluorescent diagnostics in breast cancer: pros and cons].}, journal = {Khirurgiia}, volume = {}, number = {2. Vyp. 2}, pages = {55-60}, doi = {10.17116/hirurgia202402255}, pmid = {38380465}, issn = {0023-1207}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/surgery ; Sentinel Lymph Node Biopsy ; Lymph Nodes/pathology ; Indocyanine Green ; Coloring Agents ; }, abstract = {OBJECTIVE: To analyze the effectiveness of identifying the sentinel lymph node in breast cancer using the «MARS» system for fluorescent diagnostics in near infrared light.

MATERIAL AND METHODS: There were 51 patients with breast cancer cT0-2N0M0 between July 2023 and October 2023. Mean age of patients was 52.3 years. Invasive ductal carcinoma was diagnosed in 39 (76.5%) patients, invasive lobular carcinoma - in 8 (15.7%) patients, other forms of breast cancer - in 4 (7.8%) patients.

RESULTS: Sentinel lymph node was successfully identified in all cases (n=51). A total of 122 sentinel lymph nodes were detected and mapped (2.4 nodes per a patient).

CONCLUSION: The MARS system for intraoperative fluorescence diagnostics in near-infrared light is effective for identifying the sentinel lymph node in breast cancer.}, } @article {pmid38384043, year = {2023}, author = {Soman, PS and Hemalatha, A and Sreeramulu, PN}, title = {Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S706-S711}, doi = {10.4103/jcrt.jcrt_639_22}, pmid = {38384043}, issn = {1998-4138}, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.

AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.

MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.

RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.

CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.}, } @article {pmid38384039, year = {2023}, author = {Kathimanda, ST and Hussain, N and Bugalia, A and Sarangi, S}, title = {Role of breast ultrasonography in predicting accurate tumor dimensions in correlation with histopathology and its impact on staging of breast carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S682-S684}, doi = {10.4103/jcrt.jcrt_938_22}, pmid = {38384039}, issn = {1998-4138}, abstract = {BACKGROUND AND OBJECTIVES: Estimation of the preoperative size of a breast tumor is of primary importance in deciding the treatment modality. Hence, clinical examination of the lump aided by the imaging is necessary. Our study is instrumental in correlating the size of breast tumor by high-resolution ultrasonography (USG) with the morphological size and also in comparing clinical staging of breast carcinoma against the gold standard pathological staging.

METHODS: It is a cross-sectional study of correlating the size of tumor on USG with the morphological size of biopsy proven invasive ductal carcinoma when received after excision. The size of the tumor was measured grossly and was compared with the USG measurements and palpatory findings.

RESULTS: Seventy percent of cases had good correlation between the USG and morphological size. In 50% of cases, the size on physical examination corroborated with the USG findings and only in 40% of the cases size on physical examination matched with morphological findings. In 65% of cases, the clinical staging of the breast carcinoma matched with the pathological staging. Our study reflected that USG promised to be the most useful radiological tool in predicting the accurate preoperative size of the tumor.

INTERPRETATION AND CONCLUSION: We observed that USG has proved to be a very useful conjunct to clinical examination as only palpation was not found to be very accurate in predicting the actual tumor size. It proved to be safer and cheaper and effectively instrumental in meting out an effective management at pre- and postoperative level to the patient.}, } @article {pmid38379333, year = {2024}, author = {Zhu, S and Xu, N and Zeng, H}, title = {Molecular complexity of intraductal carcinoma of the prostate.}, journal = {Cancer medicine}, volume = {13}, number = {2}, pages = {e6939}, doi = {10.1002/cam4.6939}, pmid = {38379333}, issn = {2045-7634}, support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.}, } @article {pmid38379091, year = {2024}, author = {Bufman, H and Faermann, R and Halshtok-Neiman, O and Shalmon, A and Gotlieb, M and Samoocha, D and Yagil, Y and Feldman, DM and Friedman, E and Sklair-Levy, M}, title = {Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {38379091}, issn = {1573-7217}, abstract = {PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.

METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed.

RESULTS: Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age ± SD 73.7 ± 3.3 years (range 70-90 years), followed for an average of 3.8 years (range 1-11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72 ± 2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these ten cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29 ± 0.75 cm, with IDC and DCIS diagnosed in five cases each, and none had lymph node involvement.

CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.}, } @article {pmid38378247, year = {2024}, author = {Nguyen, NJ and Liu, K and Lajkosz, K and Iczkowski, KA and van der Kwast, TH and Downes, MR}, title = {Addition of cribriform pattern 4 and intraductal prostatic carcinoma into the CAPRA-S tool improves post-radical prostatectomy patient stratification in a multi-institutional cohort.}, journal = {Journal of clinical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1136/jcp-2023-209222}, pmid = {38378247}, issn = {1472-4146}, abstract = {AIMS: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.

METHODS: A retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC. Patients were classified, after calculating the CAPRA-S scores, into low-risk (0-2), intermediate-risk (3-5) and high-risk (6-12) groups. Kaplan-Meier curves were created to estimate biochemical recurrence (BCR)-free survival. Prognostic performance was examined using Harrell's concordance index, and the effects of CC/IDC within each risk group were evaluated using the Cox proportional hazards models.

RESULTS: Our cohort included 825 prostatectomies (grade group (GG)1, n=94; GG2, n=475; GG3, n=185; GG4, n=13; GG5, n=58). CC/IDC was present in 341 (41%) prostatectomies. With a median follow-up of 4.2 years (range 2.9-6.4), 166 (20%) patients experienced BCR. The CAPRA-S low-risk, intermediate-risk and high-risk groups comprised 357 (43%), 328 (40%) and 140 (17%) patients, and discriminated for BCR-free survival (p<0.0001). For CAPRA-S scores 3-5, the addition of CC/IDC status improved stratification for BCR (HR 2.27, 95% CI 1.41 to 3.66, p<0.001) and improved the overall c-index (0.689 vs 0.667, analysis of variance p<0.001).

CONCLUSION: The addition of CC/IDC into the CAPRA-S classification significantly improved post-radical prostatectomy patient stratification for BCR among the intermediate-risk group (CAPRA-S scores 3-5). The reporting of CC and IDC should be included in future prostate cancer stratification tools for improved outcome prediction.}, } @article {pmid38376291, year = {2023}, author = {Piracha, ZZ and Saeed, U}, title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1870-1879}, pmid = {38376291}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Leucine ; beta Catenin ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Prognosis ; Proto-Oncogene Proteins c-akt ; Immunoglobulin Domains ; *Carcinoma, Ductal ; Membrane Glycoproteins ; }, abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.

METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-β/β-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.

RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-β/β-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.

CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.}, } @article {pmid38376280, year = {2023}, author = {Bhatia, M and Ahmed, R and Nagarajakumar, A and Alani, A and Doddi, S and Metafa, A}, title = {Measurement of malignant spiculated mass lesions on mammogram: Do we include the length of the spicules?.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1794-1796}, doi = {10.4103/jcrt.jcrt_2052_21}, pmid = {38376280}, issn = {1998-4138}, abstract = {AIM: The aim of this study is to determine if the core size or size with spicules has a better correlation with the final histologic size of spiculated mass lesions.

METHODS: A retrospective study of 48-month duration from January 2014 to December 2017 of biopsy-proven invasive ductal carcinoma presenting as spiculated mass lesions on mammogram was conducted.

RESULTS: There were 195 patients in the study. The mean of the core size was 16.6 mm; when spicules were included the mean size was 27.4mm and final histologic size 21.1 mm. Using unpaired Student 't' test difference in the means was statistically significant (p<0.0001). Pearson number (R) core size versus final histologic size was 0.535 (P < 0.001) and for size with spicules versus final histologic size was 0.495 (P < 0.001).

CONCLUSION: Our study demonstrated that the core size has a stronger positive correlation to final histologic size and should be used preoperatively in decision-making about surgery.}, } @article {pmid38370290, year = {2024}, author = {Khalid, IB and Sarwar, A and Khalid, HB and Sajjad, B and Rehman, B and Parvaiz, MA}, title = {Clinicopathological Features and Treatment Outcomes of Male Breast Cancer in Pakistani Population: A 10-Year Retrospective Cross-Sectional Study.}, journal = {Breast cancer : basic and clinical research}, volume = {18}, number = {}, pages = {11782234241233120}, pmid = {38370290}, issn = {1178-2234}, abstract = {BACKGROUND: Male breast cancer (MBC) accounts for 1% of global breast cancer cases. On account of its rarity, very few prospective clinical trials have been carried out on MBC. Pakistan has the highest incidence of breast cancer in Asia, but very limited data are available on MBC.

OBJECTIVES: The objective is to determine the clinicopathological characteristics and treatment patterns of MBC in Pakistani population.

DESIGN: This is a retrospective cross-sectional study.

METHODS: A retrospective cross-sectional study carried out using the cancer database of Shaukat Khanum Memorial Cancer Hospital & Research Center. Men with a histologically proven breast cancer, stage 0 to III disease and requiring surgical intervention were included. The Kaplan-Meier curve and log-rank test were used for survival analysis.

RESULTS: Sixty-eight patients with MBC were included with a median age at diagnosis of 55 years. Most patients were stage II (47.1%). Invasive ductal carcinoma (IDC) was the commonest type (89.7%). Estrogen receptor (ER), progesterone receptor (PR), and Her-2 receptor positivity were 92.6%, 86.8%, and 32.4%, respectively. Mastectomy was performed in 95.6% of the cases. Neoadjuvant and adjuvant chemotherapy was administered in 25 (36.8%) and 26 (38.2%) patients, respectively. Fifty-five (80.9%) patients received adjuvant radiotherapy. Most of the patients (89.7%) received tamoxifen. The 5-year overall and disease-free survival was 88.2% and 80.9%, respectively. Patients receiving neoadjuvant chemotherapy had a better overall and disease-free survival (P = .025).

CONCLUSIONS: Male breast cancer occurs at a relatively earlier age in Pakistani population as compared with Western men. Mastectomy is the preferred surgical option for MBC on account of the advanced disease and delayed presentation. Neoadjuvant chemotherapy has a statistically significant effect on overall and disease-free survival, but in spite of these benefits, it remains underutilized.}, } @article {pmid38369589, year = {2024}, author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ}, title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4042}, pmid = {38369589}, issn = {2045-2322}, mesh = {Humans ; *Transcription Factors/metabolism ; LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Glycolysis ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; }, abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.}, } @article {pmid38375814, year = {2023}, author = {Huang, T and Lu, C and Zhang, Y and Lin, BY and Zhang, ZJ and Zhu, D and Wang, L and Lu, Y}, title = {Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2250987}, doi = {10.1080/07853890.2023.2250987}, pmid = {38375814}, issn = {1365-2060}, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.

METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).

RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p < 0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p = 0.035).

CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.}, } @article {pmid38368743, year = {2024}, author = {Shoshani, A}, title = {The roots of compassion in early childhood: Relationships between theory of mind and attachment representations with empathic concern and prosocial behavior.}, journal = {Journal of experimental child psychology}, volume = {242}, number = {}, pages = {105880}, doi = {10.1016/j.jecp.2024.105880}, pmid = {38368743}, issn = {1096-0457}, abstract = {This study focused on attachment representations and theory of mind as potential developmental origins of individual differences in preschoolers' peer- and adult-directed empathic concern and prosocial behavior. In two experiments, 3- to 6-year-olds were exposed to either a high-distressed or low-distressed adult or child using a laboratory setting (Experiment 1; N = 263) or hypothetical vignettes (Experiment 2; N = 202). Self-reported and coded expressions of empathic concern and prosocial behaviors were used as early indicators of compassion. The findings indicated that children expressed more empathic concern and engaged in more prosocial behavior in the high-distress condition than in the low-distress condition. Children's empathic concern and prosocial behavior increased with age. Secure attachment and theory of mind abilities played significant moderating roles in the association between distress conditions and empathic concern. Children with more advanced theory of mind abilities and secure attachment were better at recognizing the concerns of distressed peers or adults and showed significantly more empathic concern. Resistant and disorganized children exhibited more self-distress in response to others' distress. The implications for early interventions directed at increasing empathic concern and prosocial behavior are discussed.}, } @article {pmid38368669, year = {2024}, author = {Gomez, D and Seneviratne, S}, title = {Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.}, journal = {International journal of surgery case reports}, volume = {116}, number = {}, pages = {109397}, doi = {10.1016/j.ijscr.2024.109397}, pmid = {38368669}, issn = {2210-2612}, abstract = {INTRODUCTION & IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.

CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.

CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.

CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.}, } @article {pmid38363600, year = {2024}, author = {Sahin, SI and Balci, S and Guler, G and Altundag, K}, title = {Clinicopathological analysis of 38 male patients diagnosed with breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {1-8}, doi = {10.3233/BD-230050}, pmid = {38363600}, issn = {1558-1551}, abstract = {BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival.

OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes.

METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained. Cut-off values of 1% and 10% are applied to further classify ER and PR results.

RESULTS: Older men are more likely to develop MBC than younger men and are more likely to have spread to axillary lymph nodes. Invasive ductal carcinoma is a more common histologic type in MBC. All the tested patients have ER and PR positivity. Distant metastasis developed in 17/38 (44.7%) patients. Bone metastasis is seen commonly in metastatic MBC.

CONCLUSIONS: According to our cohort, MBC is seen in older males, presents in later stages, and shows hormone receptor positivity and a tendency to bone involvement. MBC is a heterogenous but distinct biological entity requiring a specific clinical and pathological approach.}, } @article {pmid38361878, year = {2023}, author = {Abusanad, A}, title = {Utilizing peripheral blood inflammatory biomarker (PBIB) to predict response to systemic therapy in patients with breast cancer.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {12}, pages = {3368-3373}, doi = {10.4103/jfmpc.jfmpc_1125_23}, pmid = {38361878}, issn = {2249-4863}, abstract = {BACKGROUND: Inflammation is a recognized factor in cancer progression and resistance to treatments. Several studies correlated inflammation-related peripheral blood inflammatory biomarkers (PBIB) to disease progression and poor survival in various cancer types and different populations. Nonetheless, inflammation is affected by the distinctive characteristics and environmental exposure of each population. There is no prior study addressing the association of pre-treatment inflammatory markers with outcomes in patients with breast cancer (BC) from Saudi Arabia. In this study, we evaluated the prognosis of locally advanced breast cancer (LABC) in relation to several PBIB.

MATERIALS AND METHODS: We retrospectively analyzed the data of female patients with LABC undergoing neoadjuvant chemotherapy (NACT). Demographics, body mass index (BMI), clinicopathologic characteristics and stage of the tumor, follow-up status, and response to treatment were collected. Outcomes were evaluated in relation to pre-treatment peripheral blood indices that were grouped based on the local laboratory cutoff values. Objective response rate (ORR) was predefined and assessed according to the post-NACT magnetic resonance imaging (MRI) breast and subcategorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

RESULTS: A total of 172 female patients with BC met the eligibility criteria from January 2014 to December 2019. The mean age at diagnosis was 53.4 ± 11, and BMI was 31.2 ± 6. Left BC accounted for 54.7%, and the majority was invasive ductal carcinoma (85.5%), moderately differentiated (51%), stage III (AJCC 8[th] edition) (73%), and estrogen receptor (ER)-positive tumor (79.1%). Human epidermal growth factor receptor 2 (HER2)-positive BC was reported in 32% and triple-negative breast cancer (TNBC) in 10%. Radiologic CR accounted for the majority of ORR (71.5%). Higher percentage of patients with normal red cell distribution width (RDW) of red blood cell (RBC) and low neutrophil-lymphocyte ratio (NLR) had CR with a significant P value of 0.003 and 0.014, respectively.

CONCLUSION: Among several peripheral blood indices, RDW and NLR significantly influenced ORR. They can be explored further to potentially predict response after systemic therapy in patients with LABC. The great advantage of these biomarkers stems from their availability and affordability in routine clinical practice.}, } @article {pmid38361780, year = {2024}, author = {Wilson, KL and Grewelle, RE and Gupta, T and Kim, SH and Katsumoto, TR}, title = {Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1189287}, doi = {10.3389/fonc.2024.1189287}, pmid = {38361780}, issn = {2234-943X}, abstract = {Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.}, } @article {pmid38360632, year = {2024}, author = {Yuan, H and Zhang, R and Li, N and Yao, H}, title = {Primary fallopian tube cancer followed by primary breast cancer in RAD51C mutation carrier treated with niraparib as first line maintenance therapy: a case report.}, journal = {Hereditary cancer in clinical practice}, volume = {22}, number = {1}, pages = {2}, pmid = {38360632}, issn = {1731-2302}, support = {No. CFA202202018//Chinese Academy of Medical Sciences Cancer Hospital - Shenzhen Hospital Cooperation Fund/ ; No. 2021-RW310-002//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Medical Sciences/ ; }, abstract = {Given the rarity of RAD51C mutations, the risk and treatment of metachronous breast cancer after the diagnosis of ovarian cancer in RAD51C mutation carriers is not clear, especially for those who have received PARPi treatment. We report the case of a 65-year-old woman diagnosed with stage IIIC high-grade serous primary fallopian tube cancer. The patient had no family history of breast or ovarian cancer. The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response. After interval debulking surgery, the patient received three cycles of adjuvant chemotherapy. Collection and extraction of saliva DNA for next-generation sequencing identified a RAD51C mutation c.838-2 A > G. The patient received niraparib as front-line maintenance treatment. After 36 months of niraparib treatment, the patient had grade II invasive ductal carcinoma of the left breast that was positive for estrogen receptor (90%) and Ki-67 (30%) and negative for progesterone receptor and human epidermal growth factor receptor 2. Computed tomography revealed the absence of distant metastases. Modified radical mastectomy and axillary lymph node dissection were then performed. The final pathological report of the breast showed a 1.8 cm Bloom-Richardson grade II invasive ductal carcinoma in the left breast with axillary lymph node metastasis (1/21). Finally, the breast cancer was stage IIA, pT1cN1M0. The metachronous breast cancer in this case may be the first report of second primary cancer in fallopian tube cancer patient harboring a RAD51C mutation during niraparib treatment. Further studies are required to determine optimal treatment.}, } @article {pmid38351793, year = {2023}, author = {Aleksiev, T and Ivanova, Z and Dobrev, H}, title = {Asynchronous bilateral male breast cancer. A rare case report.}, journal = {Folia medica}, volume = {65}, number = {6}, pages = {1011-1014}, doi = {10.3897/folmed.65.e96190}, pmid = {38351793}, issn = {1314-2143}, mesh = {Male ; Humans ; Aged ; *Breast Neoplasms, Male/diagnostic imaging/therapy ; Mastectomy ; Mammography ; *Carcinoma/surgery ; *Carcinoma, Ductal/surgery ; }, abstract = {We describe a rare case of asynchronous bilateral carcinoma of the mammary glands in a 66-year-old man. The patient was admitted to the Department of Dermatology and Venereology due to exacerbation of chronic eczema. During the examination, a 3×2-cm tumor with retraction of the mammilla was found in the right mammary gland. Mastectomy and regional lymphatic dissection were performed. Histological examination showed invasive ductal carcinoma, ER (+) 70%, PR (-), HER2 (-). Treatment included chemotherapy, radiotherapy, and hormone therapy. Three years later, the patient reported a lump in the left breast. The presence of a tumor formation was confirmed by mammography and ultrasound examination. A radical mastectomy with regional lymphatic dissection was performed. Histological examination showed invasive ductal carcinoma of the mammary gland, ER (3+) 80%, PP (2+) 60%, HER2 (+++), and Ki67 (+) 80%. Treatment with chemotherapy and radiation therapy was carried out. Five years after diagnosis of the second carcinoma, the patient is in a good general condition. Regardless of its rarity, the described case should draw doctors' attention to this pathology. Assessment of risk factors and periodic breast examination in men would allow early diagnosis, timely treatment, and better prognosis of the disease.}, } @article {pmid38348593, year = {2024}, author = {Schweiger, M and Arredondo-Lasso, MN and Friano, ME and Gil-Lozano, M and Herzig, S and Uhlenhaut, NH}, title = {Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.14818}, pmid = {38348593}, issn = {1873-3468}, support = {UH 275/6-1-ID 457050056//German Research Foundation DFG/ ; TRR333 BATEnergy ID 450149205//German Research Foundation DFG/ ; TRR205 Adrenal Gland ID 314061271//German Research Foundation DFG/ ; CRC1064 Chromatin Dynamics ID 213249687//German Research Foundation DFG/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.}, } @article {pmid38344422, year = {2024}, author = {Akhgarjand, C and Anoushirvani, A and Tavakoli, A and Ghorbi, MD}, title = {Breast Cancer and Chronic Lymphocytic Leukemia and Renal Cell Carcinoma: A Case Report of a Rare Cancer Combination.}, journal = {Case reports in oncology}, volume = {17}, number = {1}, pages = {232-238}, pmid = {38344422}, issn = {1662-6575}, abstract = {INTRODUCTION: The incidence of second malignancies in breast cancer survivors has increased because of early detection and improved cancer treatment modalities. The synchronous occurrence of chronic lymphocytic lymphoma (CLL) and renal cell carcinoma (RCC) in the same patient is higher than in the general population. Several factors, including the history of chemotherapy with alkylating agents, genetic alteration, and long-term survival of breast cancer patients may explain this condition, but further research is needed.

CASE PRESENTATION: In the present report, we discussed the case of a 48-year-old female who had clear cell RCC; 5 months after the diagnosis of CLL and 15 years after invasive ductal carcinoma.

CONCLUSION: Considering the continued elevated risk of second cancers in patients with breast cancer and CLL in a clinical setting, clinicians should be made aware of ongoing medical surveillance.}, } @article {pmid38343885, year = {2023}, author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S}, title = {Breast cancer in a Hispanic patient with Werner syndrome.}, journal = {Journal of radiology case reports}, volume = {17}, number = {10}, pages = {21-31}, pmid = {38343885}, issn = {1943-0922}, abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.}, } @article {pmid38336663, year = {2024}, author = {Ye, C and Shi, M and Xie, D and Wu, H and Chen, Q and Yang, L}, title = {A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.}, journal = {BMC musculoskeletal disorders}, volume = {25}, number = {1}, pages = {118}, pmid = {38336663}, issn = {1471-2474}, support = {82372431//National Natural Science Foundation of China/ ; 2022LJ007//Shanghai Municipal Health Commission Health Leading Talents Program/ ; 22ZR1476700//the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality/ ; 201409003200//the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality/ ; 0906//the Fifth Round Innovation Team of Shanghai Changning District, the Pyramid Talent Project of Shanghai Changzheng Hospital in 2020/ ; 2021X002//the Discipline Team Support Project of No. 905 Hospital of PLA Navy/ ; }, abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.

CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.

CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.}, } @article {pmid38336012, year = {2024}, author = {Tank, P and Vora, S and Tripathi, S and D'Souza, F}, title = {Qualification of a LC-HRMS platform method for biosimilar development using NISTmab as a model.}, journal = {Analytical biochemistry}, volume = {}, number = {}, pages = {115475}, doi = {10.1016/j.ab.2024.115475}, pmid = {38336012}, issn = {1096-0309}, abstract = {Biosimilars are a cost-effective alternative to biopharmaceuticals, necessitating rigorous analytical methods for consistency and compliance. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is a versatile tool for assessing key attributes, encompassing molecular mass, primary structure, and post-translational modifications (PTMs). Adhering to ICH Q2R1, we validated an LC-HRMS based peptide mapping method using NISTmab as a reference. The method validation parameters, covering system suitability, specificity, accuracy, precision, robustness, and carryover, were comprehensively assessed. The method effectively differentiated the NISTmab from similar counterparts as well as from artificially introduced spiked conditions. Notably, the accuracy of mass error for NISTmab specific complementarity determining region peptides was within a maximum of 2.42 parts per million (ppm) from theoretical and the highest percent relative standard deviation (%RSD) observed for precision was 0.000219 %. It demonstrates precision in sequence coverage and PTM detection, with a visual inspection of total ion chromatogram approach for variability assessment. The method maintains robustness when subjected to diverse storage conditions, encompassing variations in column temperature and mobile phase composition. Negligible carryover was noted during the carryover analysis. In summary, this method serves as a versatile platform for multiple biosimilar development by effectively characterizing and identifying monoclonal antibodies, ultimately ensuring product quality.}, } @article {pmid38329829, year = {2024}, author = {Fang, L and Simman, R and Workman, L and Ayoub, S and Bratton, C}, title = {Malignant wound aetiology, diagnosis and management: a case series and literature review.}, journal = {Journal of wound care}, volume = {33}, number = {2}, pages = {102-117}, doi = {10.12968/jowc.2024.33.2.102}, pmid = {38329829}, issn = {0969-0700}, abstract = {OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.

METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.

RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.

CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.}, } @article {pmid38307851, year = {2024}, author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J}, title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {997}, pmid = {38307851}, issn = {2041-1723}, support = {R01 AI153433/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; }, abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.}, } @article {pmid38329532, year = {2024}, author = {Guerra, J and Matta, L and Bartelt, A}, title = {Cardiac proteostasis in obesity and cardiovascular disease.}, journal = {Herz}, volume = {}, number = {}, pages = {}, pmid = {38329532}, issn = {1615-6692}, abstract = {Cardiovascular diseases (CVD) are closely linked to protein homeostasis (proteostasis) and its failure. Beside genetic mutations that impair cardiac protein quality control, obesity is a strong risk factor for heart disease. In obesity, adipose tissue becomes dysfunctional and impacts heart function and CVD progression by releasing cytokines that contribute to systemic insulin resistance and cardiovascular dysfunction. In addition, chronic inflammation and lipotoxicity compromise endoplasmic reticulum (ER) function, eliciting stress responses that overwhelm protein quality control beyond its capacity. Impairment of proteostasis-including dysfunction of the ubiquitin-proteasome system (UPS), autophagy, and the depletion of chaperones-is intricately linked to cardiomyocyte dysfunction. Interventions targeting UPS and autophagy pathways are new potential strategies for re-establishing protein homeostasis and improving heart function. Additionally, lifestyle modifications such as dietary interventions and exercise have been shown to promote cardiac proteostasis and overall metabolic health. The pursuit of future research dedicated to proteostasis and protein quality control represents a pioneering approach for enhancing cardiac health and addressing the complexities of obesity-related cardiac dysfunction.}, } @article {pmid38327751, year = {2024}, author = {Zhang, M and Sun, Y and Wu, H and Xiao, J and Chen, W and Wang, H and Yang, B and Luo, H}, title = {Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1319981}, doi = {10.3389/fonc.2024.1319981}, pmid = {38327751}, issn = {2234-943X}, abstract = {BACKGROUND: Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT).

METHODS: Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model.

RESULTS: The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05).

CONCLUSION: For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.}, } @article {pmid38326829, year = {2024}, author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L}, title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.}, journal = {Cell communication and signaling : CCS}, volume = {22}, number = {1}, pages = {100}, pmid = {38326829}, issn = {1478-811X}, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.

METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.

RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.

CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.}, } @article {pmid38318566, year = {2024}, author = {Youh, J and Yamaguchi, Y and Hiraguchi, E}, title = {Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51641}, pmid = {38318566}, issn = {2168-8184}, abstract = {Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.}, } @article {pmid38313690, year = {2024}, author = {Lind, M and Folmo, EJ and Kaufman, EA}, title = {Editorial: Self-understanding and other-understanding in personality pathology.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1328860}, pmid = {38313690}, issn = {1664-0640}, } @article {pmid38311000, year = {2024}, author = {Cavaller, L and Goupille, C and Arbion, F and Vilde, A and Body, G and Ouldamer, L}, title = {Metastatic Profiles and Survival Differences Between Infiltrating Ductal Carcinoma and Infiltrating Lobular Carcinoma in Invasive Breast Cancer.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {}, number = {}, pages = {102740}, doi = {10.1016/j.jogoh.2024.102740}, pmid = {38311000}, issn = {2468-7847}, abstract = {BACKGROUND: In this study, we conducted a comprehensive evaluation of metastatic profiles and survival outcomes in patients with infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) treated at our university hospital center.

METHODS: We collected and analyzed data from all patients diagnosed with invasive breast cancer at our center between January 1, 2007, and 31 December, 2014. We specifically compared three subgroups: patients with IDC, patients with ILC and patients with mixed carcinoma, which is a combination of IDC and ILC.

RESULTS: Among the 1963 patients treated for invasive breast cancer in our center during the study period, 1435 had IDC, 466 had ILC, and 59 had mixed carcinoma. The incidence of patients with at least one positive axillary lymph node differed significantly: 40% for IDC, 36% for ILC, and 45% for mixed carcinoma (p=0.001). However, there was no significant difference in the mean number of positive nodes (p=0.1633). The occurrence of distant metastases was lower in patients with ILC (p=0.04), particularly in the case of brain metastases (p=0.01), although there was no difference in bone or visceral metastatic sites. Patients with ILC exhibited a longer mean time to metastasis from the initial diagnosis of invasive breast carcinoma. Overall survival (p=0.0525) and survival without locoregional recurrence (p=0.026) were significantly different. Specifically, the 5-year overall survival rates for IDC, ILC, and mixed carcinoma were approximately 95%. Distance metastatic-free survival at 5 years was 85% for IDC, 91% for ILC, and 87% for mixed carcinoma (p=0.00506).

CONCLUSION: Our findings indicate variations in the distribution of distant metastatic sites among patients with IDC, ILC, and mixed carcinoma, as well as differences in survival outcomes. This study sheds light on the unique characteristics and clinical implications associated with these two distinct subtypes of invasive breast cancer.}, } @article {pmid38308423, year = {2024}, author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA}, title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.}, journal = {Cancer medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/cam4.6852}, pmid = {38308423}, issn = {2045-7634}, support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; }, abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).

METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.

RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable = 32, VUS = 89) and 223 variants in the non-cancer cohort (actionable = 25, VUS = 188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p < 0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.

CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.}, } @article {pmid38306823, year = {2024}, author = {Nimbalkar, R and Baheti, AM and Pawar, AT and Tagalpallewar, AA and Nimbalkar, MR}, title = {Eleven years of disease free survival in a case of Invasive Ductal Carcinoma (IDC) Rt Breast grade 3, stage 3, treated with add on Ayurveda treatment: A case report.}, journal = {Journal of Ayurveda and integrative medicine}, volume = {15}, number = {1}, pages = {100881}, doi = {10.1016/j.jaim.2023.100881}, pmid = {38306823}, issn = {0975-9476}, abstract = {Breast cancer shows high mortality, especially in women worldwide. This report discusses a case of female patient with a history of Invasive Ductal Carcinoma (IDC) Rt Breast, ER, PR negative, Grade 3 (Gr3) Stage 3 (St3) seen in our OPD treated with supporting herbo-mineral-metallic combination of Ayurveda medicines. Generally, breast cancers of such subtype and that too in Lower Outer Quadrant (LOQ) are always of a concern and can be more troublesome to the patient. When the patient came for the first time, her chief complaint was palpable lump in her right breast for previous three months. We advised her to undergo relevant investigations and, it was found to be malignant. She underwent surgery, Modified Radical Mastectomy,(MRM), followed by chemotherapy. During chemotherapy, which was Adriamycin + Cyclophosphamide (AC) protocol 4 cycles, followed by Docetaxel 4 cycles, every 21 days. After 2 cycles, she started complaints of pain in both calf regions, numbness in fingers of hand and foot, severe generalized skin rash with itching, hyperacidity and constipation. She visited our clinic again for the same, and Ayurveda treatment was started to her at this point. So, at the time of commencement of treatment, the diagnosis was "IDC Rt Breast, LOQ, Gr3 St3, ER, PR negative HER2Neu positive, post op, on chemo". After appropriate analysis based on Ayurvedic and modern parameters, she was diagnosed to have vitiation of Rakta and Pitta (Dushti avastha), due to cyto-toxic nature of (Visha exposure) chemotherapy and medication was planned accordingly, along with chemotherapy protocol. The Ayurveda treatment showed significant relief in the chemotoxicity symptoms, within one month and she could tolerate further chemotherapy cycles very conveniently. On completion of chemotherapy, she was diagnosed to have need of good immunity (Vyadhi-Kshamatva). Based on this diagnosis, Ayurveda treatment protocol was changed and this new regimen continued for almost 6 years afterwards. Laboratory and imaging investigations performed periodically showed marked improvement, and even currently not showing any abnormality. Till date, there is no recurrence and patient is living completely normally for last 11 years. As all the symptoms and investigations showed near complete improvement; it may be concluded that probably add on Ayurveda treatment (Integrative approach) proved effective in this patient of IDC. We have observed 11 years of disease-free survival and excellent quality of life in this patient and still ongoing.}, } @article {pmid38306382, year = {2024}, author = {Moreau, A and Mognetti, T and Kryza, D}, title = {Misleading FDG Uptake in Oncology Assessment: Beyond COVID-19 Vaccination-The Role of Pneumococcal Vaccination.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {3}, pages = {283-284}, doi = {10.1097/RLU.0000000000005049}, pmid = {38306382}, issn = {1536-0229}, abstract = {Here, we report the case of a 35-year-old woman who performed PET/CT 18F-FDG as an initial workup for HER2+ right breast invasive ductal carcinoma. Examination revealed multifocal breast involvement with homolateral lymph node involvement. Contralateral axillary adenopathy and diffuse splenic and osteomedullary hypermetabolism were also observed, suggesting associated lymphoma in the absence of a recent COVID-19 vaccination. Cytopuncture was discussed and finally postponed after the patient was found to have recently received a pneumococcal vaccination.}, } @article {pmid38305220, year = {2024}, author = {Tsilingiris, D and Schimpfle, L and Κender, Z and Sulaj, A and von Rauchhaupt, E and Herzig, S and Szendroedi, J and Kopf, S}, title = {Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.}, journal = {Diabetes & vascular disease research}, volume = {21}, number = {1}, pages = {14791641231223701}, doi = {10.1177/14791641231223701}, pmid = {38305220}, issn = {1752-8984}, abstract = {PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).

METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.

RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5° for males and 5.2-5.8° for females were predictive of commonly used cutoffs. The combination of ΑCC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.

CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.}, } @article {pmid38304352, year = {2024}, author = {Mogere, E and Mutebi, M and Njau, A and Mansour, MH and Abuodha, J and Okiro, P}, title = {A rare case of breast carcinoma metastasis into a meningioma in a 64-year-old female patient.}, journal = {Radiology case reports}, volume = {19}, number = {4}, pages = {1519-1523}, doi = {10.1016/j.radcr.2023.11.035}, pmid = {38304352}, issn = {1930-0433}, abstract = {This report discusses the occurrence of tumor-to-tumor metastasis-an atypical phenomenon in oncology where a secondary malignancy develops within an existing primary tumor. The case of a 64-year-old woman is presented, who, with a history of stage II invasive ductal carcinoma of the breast treated with mastectomy and chemoradiotherapy, developed neurological symptoms indicative of a secondary brain tumor. MRI and subsequent histopathological analysis post-craniotomy confirmed a meningioma with a metastatic breast carcinoma, demonstrating the clinical importance of considering tumor-to-tumor metastasis in similar patient histories.}, } @article {pmid38304030, year = {2023}, author = {Cao, T and Duan, Z and Zhu, J and Wu, J and Chen, J and Jiang, M and Lu, X and Li, Y}, title = {Case report: Urothelial injury in a female with breast cancer: a rare adverse event after the combination of paclitaxel and trastuzumab.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1258474}, doi = {10.3389/fonc.2023.1258474}, pmid = {38304030}, issn = {2234-943X}, abstract = {Several breast cancer (BC) patients showed urinary tract infection after adjuvant trastuzumab plus paclitaxel, but no case of urothelial injury has been reported. In this case, we report a 47-year-old female patient with stage I invasive ductal carcinoma in the left breast presenting with urothelial injury after the combination of trastuzumab and paclitaxel. Initially, the patient was highly suspected of having urinary tract infection as she showed abdominal and low back pain, as well as urinary irritation symptoms and hematuria. Unfortunately, the conditions were not attenuated after anti-infection therapy. Contrast-enhanced CT showed extensive exudation and edema in the bilateral renal pelvis, ureter, and bladder, together with dilatation and effusion in the renal pelvis and ureter. Cystoscopy showed extensive congestion, edema, and erosion in the bladder epithelium. Pathological analysis demonstrated slight thinning or even loss in the uroepithelial cell layer and interstitial congestion. In addition, there was growth arrest in the epithelial cells. Immunohistochemistry indicated HER2 expression in the urothelial cells. Finally, the patient was diagnosed with urothelial injury after combination of paclitaxel and trastuzumab. The symptoms were spontaneously cured with no administration of any antibiotics in the 3-month follow-up.}, } @article {pmid38303360, year = {2023}, author = {Maeda, N and Yu, X and Nabeya, M and Suyama, R and Suzuki, N and Takeda, S and Tamesa, M and Nagashima, Y and Kubo, H and Yamamoto, S and Nagano, H}, title = {[Invasive Ductal Carcinoma within a Borderline Malignancy Phyllodes Tumor-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1618-1620}, pmid = {38303360}, issn = {0385-0684}, abstract = {Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.}, } @article {pmid38303330, year = {2023}, author = {Awazu, M and Yamamoto, Y and Agawa, K and Omura, N and Nakayama, S and Idei, Y and Maeda, H}, title = {[Long-Term Survival with Distal Pancreatectomy and Postoperative Chemotherapy in a Patient of Pancreatic Invasive Ductal Adenocarcinoma of the Tail with Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1528-1530}, pmid = {38303330}, issn = {0385-0684}, abstract = {A 68-year-old man was referred to our hospital for detailed examination of the pancreatic tail tumor. The tumor was diagnosed as the pancreatic invasive ductal adenocarcinoma and the distal pancreatectomy was scheduled. During surgery, a 2 mm white nodule was observed on the posterior wall of the stomach. Intraoperative frozen section showed no obvious malignant findings, suggesting leiomyoma or gastrointestinal stromal tumor. Distal pancreatectomy with D2 lymphadenectomy was completed as planned. However, this nodule was later confirmed by permanent pathological specimen to be peritoneal dissemination of pancreatic cancer and final diagnosis was invasive ductal carcinoma of pancreatic tail, pT3, pN1a, M1 (PER), pStage Ⅳ. He received chemotherapy for 17 months. Although liver metastasis was appeared 26 months after surgery, the disease is still being controlled with chemotherapy at 33 months.}, } @article {pmid38303308, year = {2023}, author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H}, title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1462-1464}, pmid = {38303308}, issn = {0385-0684}, abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.}, } @article {pmid38303307, year = {2023}, author = {Hayakawa, T and Hasegawa, K and Maejima, K and Takatsuno, Y and Kaneko, J and Higashi, Y and Isogai, J and Tagawa, K and Yoshida, H}, title = {[A Case of Complete Remission in a Patient with Synchronous Double Cancers of the Breast and Lung].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1459-1461}, pmid = {38303307}, issn = {0385-0684}, abstract = {The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar metastasis, which led to the diagnosis synchronous double cancers of the breast and the lung. We decided to precede surgery for lung cancer because breast cancer was indicated hormonal receptor positive. Breast cancer is treated with anastrozole, thoracoscopic right upper lobectomy was performed for the lung cancer. Radiation therapy was performed for metastatic bone tumors. 13 months later, partial mastectomy sentinel lymph node biopsy performed. The histopathological diagnosis of breast cancer was pT2, pN0, cM0, pStage ⅡA, and histological response was Grade 2a. The remaining breast was treated radiation therapy. The breast cancer has not recurred and is doing well 6 months after surgery. As for primary lung cancer, 19 months have passed since surgery, and the patient is in complete remission without recurrence.}, } @article {pmid38303227, year = {2023}, author = {Adachi, K and Nagae, J and Kubota, H and Suzuki, S and Hirano, T and Sakurai, K}, title = {[Recurrent Breast Cancer with Bone Metastasis Effectively Treated with Abemaciclib plus Endocrine Therapy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1845-1847}, pmid = {38303227}, issn = {0385-0684}, abstract = {We report a case of recurrent breast cancer with bone metastasis in a premenopausal woman. A 46-year-old woman underwent mastectomy for right breast cancer 6 years ago. Histopathological diagnosis was invasive ductal carcinoma, T2N3aM0, stage ⅢC. She received adjuvant chemotherapy and irradiation followed by tamoxifen. Four and a half years after surgery, serum tumor marker levels elevated, and bone metastasis in the sacral region was revealed by PET-CT scan. After suppressing ovarian function with LH-RH agonist, we switched the endocrine therapy from tamoxifen to letrozole with a CDK4/6 inhibitor. Five months after starting administration of abemaciclib, the bone metastasis disappeared on PET-CT. The elevated tumor markers normalized and have continued to decrease. Abemaciclib combined with endocrine therapy was significantly effective as first-line treatment for premenopausal women with metastatic breast cancer.}, } @article {pmid38303226, year = {2023}, author = {Kikukawa, Y and Kawajiri, H and Tanda, H and Sakimura, C and Tendo, M and Hori, T and Nakata, B and Ishikawa, T and Hirakawa, K}, title = {[A Case of Multicentric HER2-Positive Breast Cancer with Alterations of the Intrinsic Subtype].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1842-1844}, pmid = {38303226}, issn = {0385-0684}, abstract = {In cases where there are 2 or more tumors, it is crucial to conduct core needle biopsies on each of them. A 39-year-old woman presented at our hospital with pain in her left breast. Ultrasonography(US)revealed the presence of 2 contiguous tumors: a 35 mm tumor(tumor 1)and a 20 mm tumor(tumor 2)in the AC area of the left breast. US-guided core needle biopsies(CNB)were performed. The histological findings confirmed an invasive ductal carcinoma, characterized by ER(-)/ PR(-)/HER2(3+). Neoadjuvant chemotherapy indicated tumor 1 as PD and tumor 2 as PR, and surgery was subsequently performed(Bt plus SLN). Upon histopathological examination, the findings demonstrated a non-pCR invasive ductal carcinoma, featuring an ER(+)/PR(-)/HER2(-)profile. Depending on the specific subtype identified, post-operative treatment included HER2-targeted therapy or ER/PR-targeting hormone therapy in conjunction with chemotherapy.}, } @article {pmid38303198, year = {2023}, author = {Yabe, N and Watanuki, R and Harada, Y and Kondo, A and Yanagisawa, T and Maeda, H and Kishi, M and Yoshikawa, T and Osumi, K and Kamiya, N and Sotome, K and Ishii, Y and Jinno, H and Ikeda, T and Watanabe, M}, title = {[A Case of Triple Negative Breast Cancer with Successful Control of Recurrent Disease Activity for More than Ten Years].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1759-1761}, pmid = {38303198}, issn = {0385-0684}, abstract = {A woman in her 70s underwent mastectomy plus axillary lymph node excision(Bt plus Ax)in December 2011 for left breast cancer classified as pT2N1M0, pStage ⅡB. The tumor was identified as an invasive ductal carcinoma(IDC), neural/ glial antigen 2(NG2), pT2(35 mm), INF γ, ly2, v0, g+, f+, s+, extensive intraductal component(EIC)-negative, ICT- positive, NCAT-positive, n(4/18), estrogen receptor(ER)-negative, progesterone receptor(PgR)-negative, human epidermal growth factor receptor 2(HER2)-negative, Ki-67 30-40%. Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered. The patient refused to undergo postoperative radiation therapy. Two years after the surgery, she was diagnosed as having a lung metastasis and local disease recurrence. Biopsy of the local recurrent lesion revealed the same histopathological diagnosis as before. Capecitabine was selected for treatment of the recurrent lesion. After 2 years of capecitabine treatment, the response was rated as progressive disease (PD). At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT). This resulted in disappearance of the tumor on imaging. However, considering that the histological findings did not suggest complete response(CR)and that the tumor was triple-negative(TN), we adopted a strategy of continuing the drug therapy at reduced dose level. With this strategy, the disease activity could be successfully controlled for 6.5 years. Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity). Meanwhile, a breast cancer susceptibility gene(BRCA)analysis was performed in January 2021, which was negative. Subsequently, in September 2021, we obtained a positive result for PDL1-SP142 and negative result for 22C3. About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.}, } @article {pmid38303174, year = {2023}, author = {Takeda, Y and Ohmura, Y and Katsura, Y and Shinke, G and Kinoshita, M and Aoyama, S and Kihara, Y and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K}, title = {[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1688-1690}, pmid = {38303174}, issn = {0385-0684}, abstract = {INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.

PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).

RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over Ⅲa Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.

CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.}, } @article {pmid38299501, year = {2024}, author = {Bernardino, R and Sayyid, RK and Lajkosz, K and Al-Daqqaq, Z and Tiwari, R and Cockburn, J and Leão, R and Metser, U and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through [18]F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.}, journal = {The Journal of urology}, volume = {}, number = {}, pages = {101097JU0000000000003850}, doi = {10.1097/JU.0000000000003850}, pmid = {38299501}, issn = {1527-3792}, abstract = {PURPOSE: Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT.

MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients undergoing a pretreatment [18]F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses.

RESULTS: The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01).

CONCLUSIONS: The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.}, } @article {pmid38298032, year = {2024}, author = {Gan, L and Xie, J and Li, K and Xu, Z and Wang, X and Pei, X and Xue, B}, title = {Triple-Negative or Close-to-Triple-Negative Breast Cancer Presenting as a Thick-Walled Cystic Lesion.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348241230089}, doi = {10.1177/00031348241230089}, pmid = {38298032}, issn = {1555-9823}, abstract = {Clinical and pathologic characteristics of the invasive ductal carcinoma (IDC) presenting as a thick-walled breast cyst are little known. Three female patients were included in this report. A palpable, nontender breast lump was found in all cases. While mammography showed a hyperdense mass, ultrasonography demonstrated a thick-walled cystic mass. Magnetic resonance imaging clearly showed the cystic breast lesions with ring-like or irregular rim enhancement. A grade III IDC was confirmed in all cases. All IDCs but one were estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative, with merely weak progesterone receptor positivity (5%) in one case. All cases underwent surgical management first and postoperative chemotherapy. Breast malignancy presenting as a thick-walled cystic mass could be a highly aggressive IDC, even triple-negative breast cancer. It is imperative for breast cancer-related practitioners to identify the potentially malignant cystic lesions timely and adopt appropriate management.}, } @article {pmid38297914, year = {2024}, author = {Alex, J and Ferguson, C and Ramjan, LM and Maneze, D and Montayre, J and Salamonson, Y}, title = {Development and psychometric evaluation of an expanded urinary catheter self-management scale: A cross-sectional study.}, journal = {Journal of advanced nursing}, volume = {}, number = {}, pages = {}, doi = {10.1111/jan.16081}, pmid = {38297914}, issn = {1365-2648}, support = {2020 Nursing & Midwifery Career Development Grant Scheme//Westmead Charitable Trust/ ; CF is supported by an NHMRC Investigator Grant 202//National Health and Medical Research Council/ ; 2018 Western Sydney Local Health District Research//Western Sydney Local Health District/ ; 2019 Integrated and Community Health Research Laun//Western Sydney Local Health District/ ; }, abstract = {AIM: To develop and test the psychometric properties of an expanded catheter self-management scale for patients with in-dwelling urinary catheters.

DESIGN: A cross-sectional validation study. Despite the utility of the original 13-item catheter self-management scale, this instrument did not include bowel management, general hygiene and drainage bag care, which are fundamental skills in urinary catheter self-management to prevent common problems resulting in unnecessary hospital presentations. The expanded catheter self-management scale was developed with 10 additional items to comprehensively assess all five essential aspects of urinary catheter self-management.

METHODS: A total of 101 adult community-dwelling patients living with indwelling urinary catheters were recruited from Western Sydney, Australia. Using exploratory factor analysis with Varimax rotation, the number of factors to be extracted from the expanded 23-item expanded catheter self-management scale was determined using a scree plot. The reliability of the overall scale and subscales was measured using Cronbach's alpha. Convergent validity was assessed using Spearman's correlations between clinical characteristics, overall scale and subscales.

RESULTS: The 23-item expanded catheter self-management scale yielded a 5-factor solution, labelled as: (i) self-monitoring of catheter function, (ii) proactive, help-seeking behaviour function, (iii) bowel self-care function, (iv) hygiene-related catheter site function and (v) drainage bag care function. Cronbach's alpha of the expanded catheter self-management scale indicating all 23 items contributed to the overall alpha value. Convergent validity results showed a negative correlation between the overall expanded catheter self-management scale and catheter-related problems.

CONCLUSION: The 5-factor structure provided a comprehensive assessment of key aspects of urinary catheter self-management essential to reduce the likelihood of catheter-related hospital presentations.

IMPLICATIONS: The expanded catheter self-management scale can be used to assess and monitor effective patient-centred interventions for optimal self-management to prevent catheter-related problems and improve the quality of life of patients.

IMPACT: Many patients start their journey of living with a urinary catheter unexpectedly and are not supported with quality information to care for their catheter. The findings of this study show the correlation between catheter self-management skills and catheter-related problems. The expanded catheter self-management scale (E-CSM) assists with analysing the self-management skills of patients living with a catheter and developing tailored interventions to prevent problems and improve their quality of life. In addition, this screening tool can be included in policies, guidelines, and care plans as a standard for improving catheter management and developing educational resources for patients.

REPORTING METHOD: STROBE checklist was used to report all aspects of this study comprehensively and accurately.

Patients living with indwelling urinary catheter and their carers have participated in surveys, interviews and co-designing interventions. This paper reports the psychometric analysis of the expanded catheter self-management scale (E-CSM) used in the patient survey as part of the main study 'Improving Quality of Life of Patients Living with Indwelling Urinary Catheters: IQ-IDC Study' (Alex et al. in Collegian, 29:405-413, 2021). We greatly value our consumers' contributions and continue to communicate the progress of the study to them. Their contributions will be acknowledged in all publications and presentations. In addition, all participants will be provided the option of receiving the interventions and publications generated from this study.}, } @article {pmid38288100, year = {2023}, author = {Chan, B and Lee, JS and Yuan, Y}, title = {Case report: An exceptional responder of low-dose continuous 5-FU in a patient with de-novo stage IV triple-negative breast cancer with liver and bone marrow failure.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1305584}, pmid = {38288100}, issn = {2234-943X}, abstract = {Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triple-negative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms.}, } @article {pmid38285778, year = {2024}, author = {El-Deek, HEM and El-Naggar, MS and Sayed, SG}, title = {Immunohistochemical Expression of Autophagy-Related Marker (LC3B) and Stem Cell Marker (CD44) in Molecular Subtypes of Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {145-152}, doi = {10.31557/APJCP.2024.25.1.145}, pmid = {38285778}, issn = {2476-762X}, abstract = {BACKGROUND: Breast cancer (BC) is among the most prevalent aggressive type of malignancy affecting females worldwide. Despite the advance in early detection and management of BC; recurrence, metastasis and mortality remains high. This may be attributed to heterogeneity of BC which explained by the presence of breast cancer stem cells (BCSCs). BCSCs is characterized by their ability of self-renewal, unlimited proliferation and their differentiation potential. BCSCs maintain their activity through process of autophagy. Autophagy is a catabolic pathway important for maintenance of cellular hemostasis in response to different stressful conditions. Autophagy allows BCSCs to adapt to different stressful conditions. So, it protects BCSCs from cytotoxic effects of anti-cancer therapy and anticancer resistance.

METHODS: Formalin-fixed paraffin embedded fifty specimens of Invasive duct carcinoma of no special type(IDC/NST) of breast was selected and immunostained with stem cell marker CD44 and autophagy related marker LC3B antibodies. Correlation with different clinicopathological, histopathological characteristics and molecular subtypes of studied specimens were evaluated.

RESULTS: Both CD44 and LC3B expression were significantly associated with lymph nodal metastasis (p =0.001 and 0.010 respectively), advanced pathological stage (p= 0.045 and 0.004 respectively) and with triple negative molecular subtype of BC (p=0.044 and 0.048 respectively). Statistically positive correlation was also found between both tumor markers expression.

CONCLUSION: Results of this study suggests that CD44 and LC3B expression play a role in the clinical behavior and progression of different molecular subtypes of BC.}, } @article {pmid38285770, year = {2024}, author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R}, title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {79-85}, doi = {10.31557/APJCP.2024.25.1.79}, pmid = {38285770}, issn = {2476-762X}, abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.}, } @article {pmid38284471, year = {2024}, author = {Shoshani, A and Kor, A and Farbstein-Yavin, S and Gvion, Y}, title = {Risk and protective factors for substance use and media addictive behaviors in adolescents during the COVID-19 pandemic.}, journal = {Journal of adolescence}, volume = {}, number = {}, pages = {}, doi = {10.1002/jad.12295}, pmid = {38284471}, issn = {1095-9254}, abstract = {OBJECTIVE: This study examined the long-term effects of the COVID-19 pandemic on adolescents' substance use, digital media use, and symptoms of internet, gaming, and social media addiction.

METHOD: A nationally representative longitudinal cohort of 1665 Israeli teens and preteens, aged 9-16, completed questionnaires assessing substance use prevalence, daily screen time, symptoms of media addiction, and potential risk and protective factors. Data were collected before the pandemic (October 2019), after the second wave lockdown (November 2020), and after the fifth wave (April 2022) in Israel.

RESULTS: The analysis documented significant increases in substance use, daily screen time, and social media addiction indices over time. Gratitude, life satisfaction, positive emotions, future orientation, grit, and secure attachment emerged as significant protective factors. Sensation-seeking, negative emotions, and mental health symptoms were identified as risk factors.

CONCLUSIONS: These findings highlight the importance of educational and public mental health services in addressing the pandemic's long-term impact on the mental health and addictive behaviors of adolescents. They also emphasize the significance of enhancing protective factors and reducing risk factors to effectively mitigate substance and digital media abuse among adolescents.}, } @article {pmid38283858, year = {2024}, author = {Qin, R and Wang, X and Fan, T and Wu, T and Lu, C and Shao, X and Yin, L}, title = {Bilateral inflammatory recurrence of HER-2 positive breast cancer: a unique case report and literature review.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1276637}, doi = {10.3389/fonc.2024.1276637}, pmid = {38283858}, issn = {2234-943X}, abstract = {Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.}, } @article {pmid38282218, year = {2024}, author = {Kool, M and Hafkamp, E and Gol, J and Aukema, EJ and Malfitano, C and Reyners, A and Hales, S and van de Poll, L and Rodin, G and de Vries, F}, title = {Managing cancer and living meaningfully (CALM): Implementation in Dutch cancer care.}, journal = {Psycho-oncology}, volume = {33}, number = {1}, pages = {e6281}, doi = {10.1002/pon.6281}, pmid = {38282218}, issn = {1099-1611}, support = {//Roparun/ ; }, abstract = {OBJECTIVE: Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands.

METHODS: In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6 months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6 months.

RESULTS: Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p = 0.006), death anxiety (p = 0.008), and anxiety (p = 0.024) was observed over time.

CONCLUSIONS: This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.}, } @article {pmid38281565, year = {2024}, author = {Dimitrov, G and Shousha, S and Troianova, P}, title = {CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.}, journal = {Experimental and molecular pathology}, volume = {}, number = {}, pages = {104885}, doi = {10.1016/j.yexmp.2024.104885}, pmid = {38281565}, issn = {1096-0945}, abstract = {BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.

AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.

METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.

RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples.

CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.}, } @article {pmid38281261, year = {2024}, author = {Cui, Y and Lin, J and Sun, D and Zhang, H and Diao, T and Fu, Q}, title = {Nomogram for predicting the overall survival and cancer-specific survival of patients with intraductal carcinoma of the prostate.}, journal = {Journal of cancer research and clinical oncology}, volume = {150}, number = {2}, pages = {45}, pmid = {38281261}, issn = {1432-1335}, support = {ZR2021QH366//project ZR2021QH366 supported by Shandong Provincial Natural Science Foundation/ ; ZR2021QH366//project ZR2021QH366 supported by Shandong Provincial Natural Science Foundation/ ; }, abstract = {PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS).

METHODS: Clinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using Kaplan‒Meier curves. Internal validation of the nomograms was verified using the bootstrap resampling method.

RESULTS: The study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model's C-index was 0.744, whereas the CSS prediction model's C-index was 0.831.

CONCLUSION: We developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.}, } @article {pmid38278448, year = {2024}, author = {Mahlow, J and Barry, M and Albertson, DJ and Jo, YJ and Balatico, M and Seasor, T and Gebrael, G and Kumar, SA and Sayegh, N and Tripathi, N and Agarwal, N and Swami, U and Sirohi, D}, title = {Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.}, journal = {Human pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.humpath.2024.01.005}, pmid = {38278448}, issn = {1532-8392}, abstract = {Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.}, } @article {pmid38276982, year = {2024}, author = {Deng, Y and Lu, Y and Li, X and Zhu, Y and Zhao, Y and Ruan, Z and Mei, N and Yin, B and Liu, L}, title = {Prediction of human epidermal growth factor receptor 2 (HER2) status in breast cancer by mammographic radiomics features and clinical characteristics: a multicenter study.}, journal = {European radiology}, volume = {}, number = {}, pages = {}, pmid = {38276982}, issn = {1432-1084}, support = {No. SHDC2020CR4069//Clinical Research Plan of SHDC/ ; No. yg2021-029//Medical Engineering Fund of Fudan University/ ; No. 21YF1404800//Shanghai Sailing Program/ ; No. 3030256001//Youth Medical Talents -Medical Imaging Practitioner Program/ ; No. 2018SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; }, abstract = {OBJECTIVES: To preoperatively evaluate the human epidermal growth factor 2 (HER2) status in breast cancer using mammographic radiomics features and clinical characteristics on a multi-vendor and multi-center basis.

METHODS: This multi-center study included a cohort of 1512 Chinese female with invasive ductal carcinoma of no special type (IDC-NST) from two different hospitals and five devices (1332 from Institution A, used for training and testing the models, and 180 women from Institution B, as the external validation cohort). The Gradient Boosting Machine (GBM) was employed to establish radiomics and multiomics models. Model efficacy was evaluated by the area under the curve (AUC).

RESULTS: The number of HER2-positive patients in the training, testing, and external validation cohort were 245(26.3%), 105 (26.3.8%), and 51(28.3%), respectively, with no statistical differences among the three cohorts (p = 0.842, chi-square test). The radiomics model, based solely on the radiomics features, achieved an AUC of 0.814 (95% CI, 0.784-0.844) in the training cohort, 0.776 (95% CI, 0.727-0.825) in the testing cohort, and 0.702 (95% CI, 0.614-0.790) in the external validation cohort. The multiomics model, incorporated radiomics features with clinical characteristics, consistently outperformed the radiomics model with AUC values of 0.838 (95% CI, 0.810-0.866) in the training cohort, 0.788 (95% CI, 0.741-0.835) in the testing cohort, and 0.722 (95% CI, 0.637-0.811) in the external validation cohort.

CONCLUSIONS: Our study demonstrates that a model based on radiomics features and clinical characteristics has the potential to accurately predict HER2 status of breast cancer patients across multiple devices and centers.

CLINICAL RELEVANCE STATEMENT: By predicting the HER2 status of breast cancer reliably, the presented model built upon radiomics features and clinical characteristics on a multi-vendor and multi-center basis can help in bolstering the model's applicability and generalizability in real-world clinical scenarios.

KEY POINTS: • The mammographic presentation of breast cancer is closely associated with the status of human epidermal growth factor receptor 2 (HER2). • The radiomics model, based solely on radiomics features, exhibits sub-optimal performance in the external validation cohort. • By combining radiomics features and clinical characteristics, the multiomics model can improve the prediction ability in external data.}, } @article {pmid38273267, year = {2024}, author = {Yang, ZJ and Xin, F and Chen, ZJ and Yu, Y and Wang, X and Cao, XC}, title = {Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {134}, pmid = {38273267}, issn = {1471-2407}, abstract = {BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.

METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.

RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.

CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.}, } @article {pmid38272241, year = {2024}, author = {Failayev, H and Ganoth, A and Tsfadia, Y}, title = {Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.}, journal = {Virus research}, volume = {}, number = {}, pages = {199330}, doi = {10.1016/j.virusres.2024.199330}, pmid = {38272241}, issn = {1872-7492}, abstract = {The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.}, } @article {pmid38273260, year = {2024}, author = {Saad, HA and Baz, A and Riad, M and Eraky, ME and El-Taher, A and Farid, MI and Sharaf, K and Said, HEM and Ibrahim, LA}, title = {Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.}, journal = {BMC immunology}, volume = {25}, number = {1}, pages = {9}, pmid = {38273260}, issn = {1471-2172}, abstract = {BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.

METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.

RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.

CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.}, } @article {pmid38271174, year = {2024}, author = {Wang, C and Xu, R and Xu, S and Meng, W and Wang, R and Zhang, X}, title = {Exploring Intrinsic Discrimination and Consistency for Weakly Supervised Object Localization.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TIP.2024.3356174}, pmid = {38271174}, issn = {1941-0042}, abstract = {Weakly supervised object localization (WSOL) is a challenging and promising task that aims to localize objects solely based on the supervision of image category labels. In the absence of annotated bounding boxes, WSOL methods must employ the intrinsic properties of the image classification task pipeline to generate object localizations. In this work, we propose a WSOL method for exploring the Intrinsic Discrimination and Consistency in the image classification task pipeline, and call it as IDC. First, we develop a Triplet Metrics Based Foreground Modeling (TMFM) framework to directly predict object foreground regions using intrinsic discrimination. Unlike Class Activation Map (CAM) based methods that also rely on intrinsic discrimination, our TMFM framework alleviates the problem of only focusing on the most discriminative parts by optimizing foreground and background regions synergistically. Second, we design a Dual Geometric Transformation Consistency Constraints (DGTC2) training strategy to introduce additional supervision and regularization constraints for WSOL by leveraging intrinsic geometric transformation consistency. The proposed pixel-wise and object-wise consistency constraint losses cost-effectively provide spontaneous supervision for WSOL. Extensive experiments show that our IDC method achieves significant and consistent performance gains compared to existing state-of-the-art WSOL approaches. Code is available at: https://github.com/vignywang/IDC.}, } @article {pmid38265547, year = {2024}, author = {Dai, Q and Feng, K and Liu, G and Cheng, H and Tong, X and Wang, X and Feng, L and Wang, Y}, title = {Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.}, journal = {Targeted oncology}, volume = {}, number = {}, pages = {}, pmid = {38265547}, issn = {1776-260X}, support = {CIFMS//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: 2021-I2M-1-014//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: LC2022A02//Beijing Hope Run Special Fund of Cancer Foundation of China/ ; }, abstract = {BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.

OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.

PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.

RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.

CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.}, } @article {pmid38263821, year = {2024}, author = {Wang, Y and Li, Y and Jiang, H and Zuo, C and Xu, W}, title = {Elevated splenic 18F-fluorodeoxyglucose positron emission tomography/computed tomography activity is associated with 5-year risk of recurrence in non-metastatic invasive ductal carcinoma of the breast.}, journal = {The British journal of radiology}, volume = {97}, number = {1153}, pages = {237-248}, doi = {10.1093/bjr/tqad015}, pmid = {38263821}, issn = {1748-880X}, support = {//The First Affiliated Hospital of Naval Medical University/ ; //Shanghai Changhai Hospital/ ; GH145-22//Guhai Plan in the 14th Five-Year Plan/ ; }, abstract = {OBJECTIVE: To construct prediction models including baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters of tumoural lesions and non-tumour lymphoid tissue for recurrence-free survival within 5 years (5y-RFS) after imaging examination in patients with invasive ductal carcinomas (IDCs) of the breast.

METHODS: The study included 101 consecutive female patients. Univariable and multivariable Cox regression were used to identify clinicopathological and metabolic parameters associated with risk of recurrence. Four prediction models based on the results of multivariable analysis were constructed and visualized as nomograms. Performance of each nomogram was evaluated using the concordance index (C-index), integrated discrimination improvement, decision curve analysis (DCA), and calibration curve.

RESULTS: N3 status, total metabolic tumour volume, the maximum standardized uptake value of spleen, and spleen-to-liver ratio were significant predictors of 5y-RFS. The nomogram including all significant predictors demonstrated superior predictive performance for 5y-RFS, with a C-index of 0.907 (95% CI, 0.833-0.981), greatest net benefit on DCA, good accuracy on calibration curves, and excellent risk stratification on Kaplan-Meier curves.

CONCLUSIONS: The model that included metabolic parameters of the spleen had the best performance for predicting 5y-RFS in patients with IDCs of the breast. This model may guide personalized treatment decisions and inform patients and clinicians about prognosis.

ADVANCES IN KNOWLEDGE: This research identifies 18F-FDG PET/CT metabolic parameters of non-tumour lymphoid tissue as predictors of recurrence in breast cancer.}, } @article {pmid38262156, year = {2024}, author = {Zeng, F and Yang, Z and Tang, X and Lin, L and Lin, H and Wu, Y and Wang, Z and Chen, M and Chen, L and Chen, L and Wu, PY and Wang, C and Xue, Y}, title = {Whole-tumor histogram models based on quantitative maps from synthetic MRI for predicting axillary lymph node status in invasive ductal breast cancer.}, journal = {European journal of radiology}, volume = {172}, number = {}, pages = {111325}, doi = {10.1016/j.ejrad.2024.111325}, pmid = {38262156}, issn = {1872-7727}, abstract = {PURPOSE: To investigate the potential of using histogram analysis of synthetic MRI (SyMRI) images before and after contrast enhancement to predict axillary lymph node (ALN) status in patients with invasive ductal carcinoma (IDC).

METHODS: From January 2022 to October 2022, a total of 212 patients with IDC underwent breast MRI examination including SyMRI. Standard T2 weight images, DCE-MRI and quantitative maps of SyMRI were obtained. 13 features of the entire tumor were extracted from these quantitative maps, standard T2 weight images and DCE-MRI. Statistical analyses, including Student's t-test, Mann-Whiney U test, logistic regression, and receiver operating characteristic (ROC) curves, were used to evaluate the data. The mean values of SyMRI quantitative parameters derived from the conventional 2D region of interest (ROI) were also evaluated.

RESULTS: The combined model based on T1-Gd quantitative map (energy, minimum, and variance) and clinical features (age and multifocality) achieved the best diagnostic performance in the prediction of ALN between N0 (with non-metastatic ALN) and N+ group (metastatic ALN ≥ 1) with the AUC of 0.879. Among individual quantitative maps and standard sequence-derived models, the synthetic T1-Gd model showed the best performance for the prediction of ALN between N0 and N+ groups (AUC = 0.823). Synthetic T2_entropy and PD-Gd_energy were useful for distinguishing N1 group (metastatic ALN ≥ 1 and ≤ 3) from the N2-3 group (metastatic ALN > 3) with an AUC of 0.722.

CONCLUSIONS: Whole-tumor histogram features derived from quantitative parameters of SyMRI can serve as a complementary noninvasive method for preoperatively predicting ALN metastases.}, } @article {pmid38256464, year = {2024}, author = {Al-Madani, SO and Jaber, M and Prasad, P and Maslamani, MJMA}, title = {The Patterns of Impacted Third Molars and Their Associated Pathologies: A Retrospective Observational Study of 704 Patients.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/jcm13020330}, pmid = {38256464}, issn = {2077-0383}, abstract = {Background: The study aims to investigate parameters in patients attending Fujairah Dental Center, including assessing the prevalence of impacted teeth, determining the frequency of associated pathological conditions, and evaluating the patterns and angulations of impacted third molars. Methods: It is a retrospective descriptive study of the panoramic radiographs of patients who attended Fujairah Dental Center for dental care between January 2011 and December 2017. The minimum age for inclusion was 17 years. Clinical records were used to obtain the demographic details of patients, such as age, gender, nationality, medical history, and smoking history. Seven hundred and four panoramic radiographs and clinical records of patients were analyzed. The age range was between 17 and 112 years old, with a mean age of 34 years (S.D 13.5). Results: Of the 704 panoramic radiographs evaluated, 236 (33.6%) X-rays showed teeth impaction with a total of 562 impacted teeth in the upper and lower jaws. Five hundred and twenty-five (93.4%) were impacted third molars, and 37 (6.5%) teeth were other kinds of impacted teeth. Females showed a higher frequency of impacted teeth (62.6%) compared to males (37.4%). The highest prevalence of impacted teeth was found in the 17-25 year age group (61%), and the prevalence declined with advancing age. Impacted third molars were more likely to occur in the mandible (57.3%) than in the maxilla (42.7%). Most of the impacted third molars were in the mesioangular position, followed by the vertical position. The evaluation of the depth of impacted third molars demonstrated that level C impaction was the most frequently seen, followed by level B impaction. Impacted third-molar teeth often presented with two roots (60.7%), followed by a single root (31.3%). An evaluation of the relationship between lower third molars and the inferior dental canal (IDC) revealed that the most frequently observed relation was interrupted (61.5%), followed by a distant relation to the ID canal, and 13% were superimposed. The most common morphological pattern of roots of the impacted third molars was either straight-type or curved and dilacerated roots (5.7%). Additionally, the most noticed pathological conditions associated with impacted teeth were carious second molars adjacent to impacted third molars (42%), which was more likely to be seen in the 17-25-year age group, with females having a higher prevalence than males.}, } @article {pmid38252633, year = {2024}, author = {Zarif, S and Abdulkader, H and Elaraby, I and Alharbi, A and Elkilani, WS and Pławiak, P}, title = {Using hybrid pre-trained models for breast cancer detection.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0296912}, pmid = {38252633}, issn = {1932-6203}, abstract = {Breast cancer is a prevalent and life-threatening disease that affects women globally. Early detection and access to top-notch treatment are crucial in preventing fatalities from this condition. However, manual breast histopathology image analysis is time-consuming and prone to errors. This study proposed a hybrid deep learning model (CNN+EfficientNetV2B3). The proposed approach utilizes convolutional neural networks (CNNs) for the identification of positive invasive ductal carcinoma (IDC) and negative (non-IDC) tissue using whole slide images (WSIs), which use pre-trained models to classify breast cancer in images, supporting pathologists in making more accurate diagnoses. The proposed model demonstrates outstanding performance with an accuracy of 96.3%, precision of 93.4%, recall of 86.4%, F1-score of 89.7%, Matthew's correlation coefficient (MCC) of 87.6%, the Area Under the Curve (AUC) of a Receiver Operating Characteristic (ROC) curve of 97.5%, and the Area Under the Curve of the Precision-Recall Curve (AUPRC) of 96.8%, which outperforms the accuracy achieved by other models. The proposed model was also tested against MobileNet+DenseNet121, MobileNetV2+EfficientNetV2B0, and other deep learning models, proving more powerful than contemporary machine learning and deep learning approaches.}, } @article {pmid38250443, year = {2023}, author = {Wang, Y and Zhang, X and Yan, Y and Niu, T and Zhang, M and Fan, C and Liang, W and Shu, Y and Guo, C and Guo, D and Bi, Y}, title = {GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1289801}, pmid = {38250443}, issn = {1664-462X}, abstract = {Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.}, } @article {pmid38247077, year = {2023}, author = {Terasawa, T and Sakurai, Y and Yanai, A and Fukuda, K and Shibuya, R}, title = {[A Case of Pathological Complete Response Following Neoadjuvant S-1 Monotherapy in an Elderly Patient with Locally Advanced Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {12}, pages = {1339-1341}, pmid = {38247077}, issn = {0385-0684}, abstract = {An 86-year-old woman was referred to our hospital after an incidental CT scan of the trunk revealed a mass in the left breast and enlarged axillary lymph nodes. A core needle biopsy(CNB)from a 2 cm mass in the left breast revealed invasive ductal carcinoma, weakly positive result for ER, negative result for PgR, and negative result for HER2. She also had multiple enlarged left supraclavicular lymph nodes and was T2N3cM0, Stage ⅢC on pretreatment evaluation. She was given the S-1 oral drug of choice, starting with 80 mg/day/4-week dosing with a 2-week rest. Eight months after the start of S-1, a partial mastectomy and sentinel lymph node biopsy were performed. Pathological findings showed a pathological complete response(ypTis/ypN0)with only a 2 mm non-invasive carcinoma remnant in the left mammary gland. S-1 is weakly recommended as primary chemotherapy for HER2-negative metastatic recurrent breast cancer, but there are no reports to date of complete response in resection cases. S-1 may be administered to patients with locally advanced breast cancer who cannot tolerate standard drug therapy and may be converted to resection after a successful response.}, } @article {pmid38233262, year = {2024}, author = {Wang, B and Fu, Y and Chen, M and Peng, S and Marra, G and Zhuang, J and Zhang, S and Guo, H and Qiu, X}, title = {The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2023.11.018}, pmid = {38233262}, issn = {1873-2496}, abstract = {OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.

METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.

RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.

CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.}, } @article {pmid38231892, year = {2024}, author = {Konwinski, L and Steenland, C and Miller, K and Boville, B and Fitzgerald, R and Connors, R and Sterling, E and Stowe, A and Rajasekaran, S}, title = {Evaluating Independent Double Checks in the Pediatric Intensive Care Unit: A Human Factors Engineering Approach.}, journal = {Journal of patient safety}, volume = {}, number = {}, pages = {}, doi = {10.1097/PTS.0000000000001205}, pmid = {38231892}, issn = {1549-8425}, abstract = {OBJECTIVES: The goal of this human factors engineering-led improvement initiative was to examine whether the independent double check (IDC) during administration of high alert medications afforded improved patient safety when compared with a single check process.

METHODS: The initiative was completed at a 24-bed pediatric intensive care unit and included all patients who were on the unit and received a medication historically requiring an IDC. The total review examined 37,968 high-risk medications administrations to 4417 pediatric intensive care unit patients over a 40-month period. The following 5 measures were reviewed: (1) rates of reported medication administration events involving IDC medications, (2) hospital length of stay, (3) patient mortality, (4) nurses' favorability toward single checking, and (5) nursing time spent on administration of IDC medications.

RESULTS: The rate of reported medication administration events involving IDC medications was not significantly different across the groups (95% confidence interval, 0.02%-0.08%; P = 0.4939). The intervention also did not significantly alter mortality (P = 0.8784) or length of stay (P = 0.4763) even after controlling for the patient demographic variables. Nursing favorability for single checking increased from 59% of nurses in favor during the double check phase, to 94% by the end of the single check phase. Each double check took an average of 9.7 minutes, and a single check took an average of 1.94 minutes.

CONCLUSIONS: Our results suggest that performing independent double checks on high-risk medications administered in a pediatric ICU setting afforded no impact on reported medication events compared with single checking.}, } @article {pmid38231374, year = {2024}, author = {Maggi, G and Vitale, C and Giacobbe, C and Barone, A and Mastromarino, C and Iannotta, F and Amboni, M and Weintraub, D and Santangelo, G}, title = {Validation of the Italian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) in an Italian Parkinson's disease cohort.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, pmid = {38231374}, issn = {1590-3478}, abstract = {INTRODUCTION: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated.

METHODS: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication.

RESULTS: Subsyndromal ICDs manifestations were observed in 54% of the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and the clinical aspects of PD and dopaminergic medication.

CONCLUSION: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD.}, } @article {pmid38229789, year = {2023}, author = {Singhal, VK}, title = {Receptor Positive Breast Lesions and Status of Axillary Lymph Node.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50645}, pmid = {38229789}, issn = {2168-8184}, abstract = {Objective This study aimed to examine the axillary pathological condition through the development of an assessment framework for hormone receptor-positive breast cancer subsequent to neoadjuvant chemotherapy (NAC). Furthermore, the primary objective of this study was to examine the association between axillary status and breast tumors that are positive for hormone receptors following neoadjuvant chemotherapy. Methodology The present retrospective investigation encompassed a cohort including 300 individuals who were administered neoadjuvant chemotherapy before receiving surgical intervention. The data collection period for this study was from September 2021 to December 2022. All patients received neoadjuvant chemotherapy, per the guidelines established by the National Comprehensive Cancer Network (NCCN). We divided patients into two distinct groups: a test set of 250 patients and a validity set of 50 patients. Patients with no evidence of lymphoid involvement underwent a biopsy of sentinel lymph nodes (SLNB) and would have undergone axillary dissection if the biopsy results had indicated positive findings. A logistic regression analysis was employed to investigate the variables linked to the presence of residual positive axillary lymph nodes in the test set. Subsequently, a multivariate analysis was conducted on the variables that exhibited a p-value below 0.2 in the univariate study. In addition, a value of 1 was assigned to all risk factors to construct a comprehensive correlation prediction model. Results The participants included in this study had a mean age and body mass index (BMI) of 46.24 ± 9.1 years and 25.8 ± 2.5 kg, respectively. The present investigation examined the presence of pathological axillary metastases in a cohort of 188 patients, which accounted for 62.55% of the total sample, by utilizing core-needle biopsy. Furthermore, the incidence rates of individuals presenting with clinical T1 were reported as 14.6%, while 55.2% cases of T2, 17.8% cases of T3, and 13% cases of T4 tumors were reported, respectively. Of the overall occurrences, the prevailing histological subtype was invasive ductal carcinoma, accounting for 91.4% (222 out of 243) of the cases. Multiple criteria were identified as independent predictors of the presence of residual positive axillary lymph nodes. The factors under consideration encompass lymphovascular invasion (odds ratio= 7.108; 95% breast cancer stage (odd ratio = 5.025; 95%, HER2 negativity (odd ratio= 2.997), low Ki-67 expression (odd ratio = 4.231), and suspected positive axillary lymph nodes before surgical intervention. Conclusion The present study presents a novel prediction model that integrates imaging and pathology data, aiming to assist patients and healthcare practitioners in evaluating the efficacy of NAC for hormone-receptor-positive breast tumors. The model holds particular significance for individuals who exhibit clinical positivity in their lymph nodes (LNs). Consequently, the model has the potential to provide guidance for the management of axillary lymph nodes and prevent unnecessary dissection.}, } @article {pmid38229073, year = {2024}, author = {Ido, M and Fujii, K and Mishima, H and Kubo, A and Saito, M and Banno, H and Ito, Y and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {85}, pmid = {38229073}, issn = {1471-2407}, abstract = {AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.

PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.

RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.

CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.}, } @article {pmid38225996, year = {2023}, author = {Wemimo, RM and Eziagu, UB and Sulaiman, OA and Abiodun, AE and Idowu, NA and Ayinde, AA and Taiwo, AA}, title = {Immunohistochemical and Clinicopathological Characteristics of Invasive Breast Carcinoma in Nigeria.}, journal = {Oman medical journal}, volume = {38}, number = {5}, pages = {e548}, pmid = {38225996}, issn = {1999-768X}, abstract = {OBJECTIVES: We aimed to study the immunohistochemical and clinicopathological characteristics of invasive breast carcinoma among Nigerian women.

METHODS: We conducted a retrospective assessment of female patients diagnosed with breast carcinoma at a tertiary hospital in Nigeria between 2012 and 2019. Archived pathology request forms and processed specimens (tissue blocks and slides) were used as source data in addition to the patients' demographic and other relevant data.

RESULTS: Reports pertaining to 113 patients were assessed. Their age range was 30 to 80 years (mean = 52.1±12.1 years). Breast carcinoma was most common in patients aged 40 to 49 years (32.7%), closely followed by those aged 50 to 59 years (30.1%). Invasive ductal carcinoma was the most common histopathological subtype (94.7%). Nottingham grade III and grade II breast carcinoma accounted for 41.6% and 40.7% of the cases, respectively. Mastectomy specimens formed 68.1% of the samples. The most common tumor size (75.9%) was > 5cm (mean = 6.8±3.2cm), consistent with the most common staging of T3 (46.0%). The most common lymph node involvement was N1 (56.6%). Immunohistochemical assessment of these tumors with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER-2) biomarkers expressed positivity of 36.3%, 28.3%, and 41.6%, respectively. These tumors were immunohistochemically classified into luminal A (16.8%), luminal B (20.4%), HER-2 enriched (20.4%), and triple-negative (42.5%) subtypes.

CONCLUSIONS: The most common immunohistochemical subtype of invasive breast carcinoma among this sample of Nigerian women was the triple-negative subtype, similar to the finding among African Americans.}, } @article {pmid38225559, year = {2024}, author = {Nisar, MI and das, S and Khanam, R and Khalid, J and Chetia, S and Hasan, T and Shahid, S and Marijani, ML and Ahmed, S and Khalid, F and Ali, SM and Chowdhury, NH and Mehmood, U and Dutta, A and Rahman, S and Qazi, MF and Deb, S and Mitra, DK and Usmani, AA and Dhingra, U and Raqib, R and Manu, A and Yoshida, S and Minckas, N and Bahl, R and Baqui, AH and Sazawal, S and Jehan, F}, title = {Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {66}, pmid = {38225559}, issn = {1471-2393}, support = {64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; 64438//Bill and Melinda Gates Foundation/ ; }, abstract = {BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa.

METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders.

RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6).

CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.}, } @article {pmid38223107, year = {2024}, author = {Yao, M and Luo, S and Li, L and Wang, Y and Zhu, W and Liu, Y and Liang, C}, title = {Sonographic and clinicopathologic features of metaplastic breast carcinoma and infiltrating ductal carcinoma: a comparative single-center cohort study.}, journal = {Quantitative imaging in medicine and surgery}, volume = {14}, number = {1}, pages = {909-919}, pmid = {38223107}, issn = {2223-4292}, abstract = {BACKGROUND: The rarity of metaplastic breast carcinoma (MBC) has resulted in limited sonographic data. Given the inferior prognosis of MBC compared to invasive ductal carcinoma (IDC), accurate preoperative differentiation between the two is imperative for effective treatment planning and prognostic prediction. The objective of this study was to assess the diagnostic accuracy of MBC and differentiate it from IDC by analyzing sonographic and clinicopathologic features.

METHODS: In this retrospective cohort study, 197 women comprising 200 IDC lesions were enrolled between January 2012 and December 2021 and 20 women comprising 20 pure MBC lesions were enrolled between January 2019 and December 2019. A comparison was made between the sonographic and clinicopathologic characteristics of MBC and IDC.

RESULTS: The results indicated that patients with MBC had a higher proportion of tumor grade 3 (95.0% vs. 32.5%; P<0.001), high Ki-67 expression (100.0% vs. 75.0%; P<0.001), and the triple-negative subtype (90.0% vs. 13.0%; P<0.001) as compared to those with IDC. On ultrasound (US) findings, MBC lesions tended to have a larger size (≥5 cm: 45.0% vs. 1.5%; P<0.001), regular shape (45.0% vs. 1.5%, P<0.001), circumscribed margin (40.0% vs. 0.5%, P<0.001), a complex cystic and solid echo pattern (50.0% vs. 3.5%; P<0.001), and posterior acoustic enhancement (95.0% vs. 14.5%; P<0.001). Additionally, MBC was more likely to be misinterpreted as a benign lesion by sonographers than was IDC (30.0% vs. 4.5%; P<0.001). Multilayer perceptron analysis revealed posterior acoustic enhancement, circumscribed margins, and size as distinguishing factors between these two tumor types. The estimated rates of local recurrence, distant metastasis, and 5-year overall survival in 19 cases with MBC were found to be 10.5%, 31.6%, and 65.0%, respectively.

CONCLUSIONS: MBC typically presents as a large breast mass with more benign US features in older women, findings which may facilitate its accurate diagnosis and differentiation from other breast masses.}, } @article {pmid38223094, year = {2024}, author = {Li, W and Zheng, Y and Liu, H and Tai, Z and Zhu, H and Li, Z and Gu, Q and Li, Y}, title = {Multimodal ultrasound imaging for diagnostic differentiation of sclerosing adenosis from invasive ductal carcinoma.}, journal = {Quantitative imaging in medicine and surgery}, volume = {14}, number = {1}, pages = {877-887}, pmid = {38223094}, issn = {2223-4292}, abstract = {BACKGROUND: Sclerosing adenosis (SA) is a common proliferative benign lesion without atypia in the breast that may mimic invasive ductal carcinoma (IDC) on medical imaging, leading to it often being misdiagnosed and mistreated. Consequently, the purpose of this study was to assess the diagnostic value of multimodal ultrasound imaging in distinguishing SA from IDC.

METHODS: Multimodal ultrasound imaging, including automated breast volume scan (ABVS), elasticity imaging (EI), and color Doppler flow imaging (CDFI), were performed on 120 consecutive patients comprising 122 breast lesions (54 SA, 68 IDC). All lesions were pathologically confirmed. Multimodal ultrasound imaging features were compared between the two groups. Binary logistic regression analysis based on ABVS, EI, and CDFI was conducted to formulate a logistic regression equation for differentiating SA from IDC. The diagnostic performances of ABVS, EI, CDFI, and their combination were compared by the receiver operating characteristic (ROC) curve analysis.

RESULTS: The sensitivity, specificity, and accuracy of ABVS, EI, CDFI, and their combination in differentiating SA from IDC were, respectively, 75.00%, 72.22%, and 73.77%; 86.76%, 72.22%, and 80.33%; 73.53%, 64.81%, and 69.67%; and 88.24%, 74.07%, and 81.97%. Combining multimodal ultrasound imaging yielded an area under the curve (AUC) of 0.895 (95% confidence interval: 0.827-0.943), which was higher than that of ABVS, EI, and CDFI, with AUC values of 0.736, 0.795, and 0.692, respectively, and the difference was statistically significant (ABVS vs. combined model, P<0.001; CDFI vs. combined model, P<0.001; EI vs. combined model, P<0.001). There was no significant difference in the diagnostic efficacy among the three imaging modalities (ABVS vs. EI, P=0.266; ABVS vs. CDFI, P=0.4671; EI vs. CDFI, P=0.051). Compared with those in IDC, the calcification (16.67% vs. 57.35%; P<0.001) and retraction phenomena in the coronal planes (18.52% vs. 57.35%; P<0.001) were less common in patients with SA, while circumscribed margin (38.89% vs. 5.88%; P<0.001), vascularity grade 0-I (64.81% vs. 26.47%; P<0.001), and elasticity scores 1-3 (72.22% vs. 13.24%; P<0.001) were more frequently found in patients with SA. Patients with SA were significantly younger than were patients with IDC (43±11 vs. 54±11 years; P<0.001), and the lesion size was smaller in patients with SA than in those with IDC (median size 1.0 cm; interquartile range (IQR), 0.9 cm vs. median size 1.3 cm; IQR, 1.3 cm; P<0.001).

CONCLUSIONS: The preliminary results suggested that multimodal ultrasound imaging can improve the diagnostic accuracy of SA and provide additional information for differential diagnosis of SA and IDC.}, } @article {pmid38222730, year = {2024}, author = {Gul, MH and Arooj, H and Siddiqui, A and Abdullah, L and Waseem, Z and Hashmi, MU}, title = {Breast cancer's hidden partner: meningoencephalitis as a paraneoplastic revelation: a rare presentation of invasive ductal carcinoma of breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {1}, pages = {512-516}, pmid = {38222730}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Paraneoplastic neurologic syndromes encompass a group of neurologic disorders arising from pathological processes unrelated to metastasis, metabolic disturbances, infections, coagulopathy, or treatment-related side effects. These syndromes can affect various regions of the nervous system, resulting in diverse clinical manifestations.

CASE PRESENTATION: The authors present a rare case of anti-amphiphysin-associated meningoencephalitis in a South Asian Pakistani woman. Initially, the patient was managed for suspected infectious meningitis, but empirical treatment failed to yield improvement. Subsequent investigations unveiled a paraneoplastic syndrome secondary to breast cancer.

DISCUSSION: Diagnosing these clinical entities is challenging due to their multifaceted presentations, often leading to delayed identification, increased patient suffering, economic burdens, and preventable complications.

CONCLUSION: Anti-amphiphysin-associated meningoencephalitis is a rare manifestation of paraneoplastic syndromes. It is crucial to raise awareness among healthcare professionals about the diverse presentations of paraneoplastic syndromes.}, } @article {pmid38216630, year = {2024}, author = {Zhang, M and Yuan, J and Wang, M and Zhang, M and Chen, H}, title = {Chemotherapy is of prognostic significance to metaplastic breast cancer.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1210}, pmid = {38216630}, issn = {2045-2322}, support = {21Y11912100//Science and Technology Innovation Plan of Shanghai Science and Technology Commission/ ; 075_ZC//a project to foster clinical research from Obstetrics and Gynecology Hospital of Fudan University/ ; }, mesh = {Female ; Humans ; Prognosis ; *Breast Neoplasms/drug therapy/pathology ; *Triple Negative Breast Neoplasms/pathology ; Treatment Outcome ; Kaplan-Meier Estimate ; Retrospective Studies ; Chemotherapy, Adjuvant/methods ; }, abstract = {This study aimed to evaluate the significance of chemotherapy (CT) among metaplastic breast cancer (MpBC), and to compare the survival outcomes between triple negative MpBC (MpBC-TNBC) and triple negative invasive ductal carcinoma (IDC-TNBC). SEER database was indexed to identify female unilateral primary MpBC diagnosed from 2010 to 2017. Patients were classified into neoadjuvant chemotherapy (NAC) with response (NAC-response), NAC-no response, adjuvant chemotherapy, and no CT. Breast cancer-specific survival (BCSS) and overall survival (OS) was estimated using the Kaplan-Meier method and compared by log-rank test. Cox regression was used to evaluate the independent prognostic factors. A 1:4 propensity score matching method was adopted to balance baseline differences. Altogether 1186 MpBC patients were enrolled, among them 181 received NAC, 647 received adjuvant CT and 358 did not receive any CT. Chemotherapy was an independent favorable prognostic factor. NAC-response and adjuvant CT had a significant or an obvious trend of survival improvement compared with NAC-no response or no CT. MpBC-TNBC was an independent unfavorable prognostic factor compared with IDC-TNBC. Among them, there was significant or trend of survival improvement among all TNBCs receiving NAC or adjuvant CT compared with no CT. Chemotherapy was of important significance to MpBC prognosis and should be integrated in comprehensive treatment for MpBC.}, } @article {pmid38215056, year = {2024}, author = {Schimpfle, L and Tsilingiris, D and Mooshage, CM and Kender, Z and Sulaj, A and von Rauchhaupt, E and Szendroedi, J and Herzig, S and Goepfert, J and Groener, J and Nawroth, PP and Bendszus, M and Heiland, S and Kurz, FT and Jende, JME and Kopf, S}, title = {Phase angle of bioelectrical impedance analysis as an indicator for diabetic polyneuropathy in type 2 diabetes mellitus.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgad737}, pmid = {38215056}, issn = {1945-7197}, abstract = {CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routine leading to increased morbidity and mortality.

OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory and physical markers of DPN to evaluate PhA as possible diagnostic method for DPN.

MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), amongst which 63 had DPN. The PhA was calculated from multi-frequency BIA. Nerve conduction studies (NCS), quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography (MRN) to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed.

RESULTS: T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, p = 0.007,  + 6.1%) and healthy controls (6.18 ± 0.08, p < 0.001,  + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=0.28; β=0.31, p < 0.001) and tibial nerves (β=0.28; β=0.32, p < 0.001), Z-scores of QST (thermal detection β=0.30, p < 0.05) and the FA (β=0.60, p < 0.001). ROC analysis showed similar performance of PhA in comparison to mentioned diagnostic methods.

CONCLUSION: The study shows that PhA is in comparison to other test systems used, at least an equally good and much easier to handle, investigator independent marker for detection of DPN.}, } @article {pmid38213367, year = {2023}, author = {Mada, SR and Zay, HH and Bies, JJ and Massebo, E and Didia, C}, title = {A Rare Case of Remittent Male Invasive Ductal Carcinoma With New Metastasis After Incomplete Adjuvant Therapy.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50400}, pmid = {38213367}, issn = {2168-8184}, abstract = {Breast cancer is a rare disease in men with many barriers to effective management such as limited research and treatment modalities. While the current standard of care utilizes mastectomy and axillary dissection with chemotherapy, clinicians must follow the female-staged breast cancer protocol, as there is no established regimen for men. In this case presentation, we report a 43-year-old male with a prior history of ER-positive invasive ductal carcinoma (IDC) who presented with a recurrent breast lesion. The patient had previously undergone left breast mastectomy with sentinel node biopsy with negative margins. The patient declined adjuvant chemotherapy and tamoxifen therapy after the initial dissection. Three years after the primary dissection, the patient presents with a breast lesion and metastasis to bilateral axillary lymph nodes, lungs, and spine. The diagnosis was supported by a right axillary biopsy which revealed an ER-positive and PR-positive lesion. We want to shed light on the importance of complete and thorough treatment of primary IDC in men while highlighting the implications of incomplete treatment. We hope that this clinical case will serve as a guide for physicians in promoting adjuvant treatments after primary tumor removal in male IDC.}, } @article {pmid38205326, year = {2024}, author = {Ibuki, E and Kadota, K and Kimura, N and Ishikawa, R and Oshima, M and Okano, K and Haba, R}, title = {Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23928}, pmid = {38205326}, issn = {2405-8440}, abstract = {Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm[2]) and at 40 × magnification (/0.237 mm[2]; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.}, } @article {pmid38213652, year = {2023}, author = {Bhatia, JK and Malik, A and Chaudhary, T and Gopal, A and Boruah, D and Singh, B}, title = {Evaluation of Number Density of Tumor-Associated Macrophages by Immunohistochemistry and Semiquantitative Scoring in Invasive Breast Cancer: An Indian Study.}, journal = {Journal of microscopy and ultrastructure}, volume = {11}, number = {4}, pages = {214-219}, pmid = {38213652}, issn = {2213-8803}, abstract = {CONTEXT: Tumor microenvironment is emerging as a critical factor for progression of breast cancer. Tumor-associated macrophages (TAMs) play an important role in promoting tumor growth.

AIM: This study was aimed at correlation of number density (ND) of TAMs with invasive ductal carcinoma (IDC) grading utilizing an image morphometric technique. We also sought to compare the TAMs and ND in the tumoral area and stromal region. We also explored the relationship between the clinical and pathological prognostic parameters.

SUBJECTS AND METHODS: The study included 75 cases of IDC that had undergone modified radical mastectomy. The Institutional Ethics Committee approved the study. Samples were classified as Grade 1, 2, and 3. Cases were graded as per the modified Bloom and Richardson criterion. Mean with standard deviation was calculated for each group. We utilized CD68 and CD163 immunostained sections for determining the ND of TAMs. TAMs were evaluated using computerized digital photomicrograph system with image analyzing software. ND was defined as the number of TAMs in total number of TAMs in five high-power fields/total area of five fields. ND was calculated separately in tumor and tumor stroma (TS). Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu) were scored in accordance with recommendations. Ki-67 was scored as per the recommended guidelines.

STATISTICAL ANALYSIS USED: Data were tabulated in Microsoft Excel. SPSS version 20.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. To determine the relationship between macrophage density and clinicopathologic parameters, we used the independent t-test. To determine the differences in the parameters, analysis of variance (ANOVA) was utilized.

RESULTS: Age of the patients ranged from 34 to 58 years (mean: 55.5). One-way ANOVA between various grades of tumor indicating significant differences in terms of CD68 and CD163 densities in tumor and stroma (P < 0.0001). i.e., significant increased density of CD68 and CD163 was observed in Grade 3 tumor as compared to other two groups. A greater histological grade, ER, PR negative status, and a high Ki-67 index were all associated with TAM ND. There was no relation to HER2/neu status. Result of unpaired t-test indicates increased density in stroma as compared to tumor among various grades of IDC.

CONCLUSIONS: We analyzed images with a software using photographs of the stained slides. This helped in quantitative analysis of TAMs on the CD68 and CD163 stained sections. This approach standardizes and reproducibly counts TAMs per unit area. We found significant difference between the number densities of TAMs in grades of invasive breast carcinoma. There were statistically significant differences in numerical densities of TAMs with ER, PR negativity, and Ki-67. There was no correlation with HER2/neu. Densities of CD68 and CD163 densities are more prevalent in TS as compared to intratumoral region.}, } @article {pmid38201445, year = {2023}, author = {Lim, GH and Hoo, JX and Shin, YC and Choo, RZT and Wong, FY and Allen, JC}, title = {Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?.}, journal = {Cancers}, volume = {16}, number = {1}, pages = {}, doi = {10.3390/cancers16010017}, pmid = {38201445}, issn = {2072-6694}, abstract = {BACKGROUND: Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge.

METHODS: A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging.

RESULTS: A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients.

CONCLUSIONS: Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.}, } @article {pmid38201413, year = {2024}, author = {Nicosia, L and Mariano, L and Bozzini, AC and Pesapane, F and Bagnardi, V and Frassoni, S and Oriecuia, C and Dominelli, V and Latronico, A and Palma, S and Venturini, M and Fontana, F and Priolo, F and Abiuso, I and Sangalli, C and Cassano, E}, title = {Radiological Features of Male Breast Neoplasms: How to Improve the Management of a Rare Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/diagnostics14010104}, pmid = {38201413}, issn = {2075-4418}, abstract = {The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35-81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid-partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing.}, } @article {pmid38200268, year = {2024}, author = {Cuoco, S and Blundo, C and Ricci, M and Cappiello, A and Bisogno, R and Carotenuto, I and Avallone, AR and Erro, R and Pellecchia, MT and Amboni, M and Barone, P and Picillo, M}, title = {Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {38200268}, issn = {1435-1463}, abstract = {OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D).

The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively.

RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57).

CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.}, } @article {pmid38196268, year = {2024}, author = {Rizzo, V and Cicciarelli, F and Galati, F and Moffa, G and Maroncelli, R and Pasculli, M and Pediconi, F}, title = {Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {}, number = {}, pages = {2841851231225807}, doi = {10.1177/02841851231225807}, pmid = {38196268}, issn = {1600-0455}, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis.

PURPOSE: To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC).

MATERIAL AND METHODS: Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome.

RESULTS: Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10[-3] mm[2]/s (P = 0.004).

CONCLUSION: Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.}, } @article {pmid38195987, year = {2024}, author = {Knödlseder, N and Fábrega, MJ and Santos-Moreno, J and Manils, J and Toloza, L and Marín Vilar, M and Fernández, C and Broadbent, K and Maruotti, J and Lemenager, H and Carolis, C and Zouboulis, CC and Soler, C and Lood, R and Brüggemann, H and Güell, M}, title = {Delivery of a sebum modulator by an engineered skin microbe in mice.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {38195987}, issn = {1546-1696}, support = {Marie Skłodowska-Curie Grant Agreement 882387//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; Award N62909-18-1-2155//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; - IdC 2019 PROD 00057//Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; Fellowship number 8240//European Molecular Biology Organization (EMBO)/ ; Award Juan de la Cierva FJC 2018-037096-I//Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)/ ; Grant Agreement 882387//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; }, abstract = {Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.}, } @article {pmid38195458, year = {2024}, author = {Hemida, AS and Shabaan, MI and Taha, MA and Abdou, AG}, title = {Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and β-catenin in infiltrating breast carcinoma of no special type.}, journal = {World journal of surgical oncology}, volume = {22}, number = {1}, pages = {15}, pmid = {38195458}, issn = {1477-7819}, abstract = {BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/β-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and β-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and β-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis.

MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and β-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and β-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered.

RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant β-catenin expression. High KIF18A and β-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and β-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low β-catenin H score.

CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating β-catenin. Overexpression of KIF18A and aberrant expression of β-catenin are considered proto-oncogenes of breast cancer development. KIF18A and β-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.}, } @article {pmid38193247, year = {2024}, author = {Okano, K and Miyai, K and Mikoshi, A and Edo, H and Ito, K and Tsuda, H and Shinmoto, H}, title = {Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {}, number = {}, pages = {}, doi = {10.1111/iju.15385}, pmid = {38193247}, issn = {1442-2042}, abstract = {OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.

METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.

RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.

CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.}, } @article {pmid38191821, year = {2024}, author = {Mooshage, CM and Schimpfle, L and Tsilingiris, D and Kender, Z and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Jende, JME and Kurz, FT}, title = {Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes.}, journal = {European radiology experimental}, volume = {8}, number = {1}, pages = {6}, pmid = {38191821}, issn = {2509-9280}, support = {SFB 1158//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).

METHODS: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data.

RESULTS: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r =  - 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r =  - 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016).

CONCLUSIONS: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D.

TRIAL REGISTRATION: https://classic.

CLINICALTRIALS: gov/ct2/show/NCT03022721 . 16 January 2017.

RELEVANCE STATEMENT: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes.

KEY POINTS: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.}, } @article {pmid38190274, year = {2024}, author = {Mancin, P and Malerba, A and Doron, G and Ghisi, M and Cerea, S}, title = {"Can I Have More Than This?" The Role of Romantic Relationship Quality, Maximization Style, and Social Media Addiction in Relationship Obsessive Compulsive Disorder Symptoms.}, journal = {Cyberpsychology, behavior and social networking}, volume = {}, number = {}, pages = {}, doi = {10.1089/cyber.2023.0348}, pmid = {38190274}, issn = {2152-2723}, abstract = {Relationship Obsessive Compulsive Disorder (ROCD) is a form of obsessive-compulsive disorder that manifests in the relationship domain, such as romantic relationships. Within romantic relationship, ROCD symptoms could be focused on flaws perceived on the relationship itself (ROCD relationship-centered) or on the partners' quality (ROCD partner-focused). These symptoms are associated with negative relationship outcomes, such as low relationship satisfaction. However, no studies have yet addressed the role of relationship quality in the context of ROCD. Furthermore, previous studies have shown the detrimental role of social media use and maximization style in obsessive-compulsive symptoms and the romantic relational domain; however, the associations with ROCD symptoms have not yet been explored. Thus, this study aimed to close this gap examining the associations between ROCD symptoms (relationship-centered and partner-focused) and relationship quality, social media addiction, and maximization style. A total of 211 participants currently involved in a romantic relationship (71.1 percent female, mean age = 30.4 ± 11.54 years) participated in the study. Multiple hierarchical regression analyses revealed that relationship quality, social media addiction, and maximization style emerged as being significantly associated with relationship-centered and partner-focused ROCD symptoms. The results highlighted potential risk factors for ROCD symptoms in romantic relationships, namely relationship quality, social media addiction, and maximization style. These psychological dimensions could be identified as possible targets in the assessment and treatment of ROCD symptoms.}, } @article {pmid38190207, year = {2023}, author = {Elshanbary, AA and Zaazouee, MS and Nourelden, AZ and Al-Kafarna, M and Matar, SG and Elsaeidy, AS and Ragab, KM and Elhady, MM and Albadrani, GM and Altyar, AE and Kensara, OA and Abdel-Daim, MM}, title = {Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {}, number = {}, pages = {}, pmid = {38190207}, issn = {1473-5709}, abstract = {BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast.

MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software.

RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV.

CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.}, } @article {pmid38187107, year = {2024}, author = {Kassem, M and Kamr, A and Wright, CB and Sobolewski, AP}, title = {Efficacy of the Radiofrequency Identification Technique in Breast Cancer Patients: A Single Institution Retrospective Study.}, journal = {European journal of breast health}, volume = {20}, number = {1}, pages = {52-56}, pmid = {38187107}, issn = {2587-0831}, abstract = {OBJECTIVE: Breast conserving surgery is an excellent option in the treatment of breast cancer. To achieve a good result with this modality, a surgeon needs to identify and excise the tumor with adequate margins. The radiofrequency identification (RFID) technique is a wireless localization technique used for intraoperative breast lesion identification. We assessed the efficacy and outcomes of the RFID technique in breast cancer patients at our institution.

MATERIALS AND METHODS: This is a single institution, retrospective study (BSMH 22-02X-MWH) of 73 patients. We analyzed the medical records of women with biopsy-proven breast cancer from June 2020 to August 2022; participants received surgical care at Mercy Health West Hospital. Data collected included demographics, clinicopathological characteristics, and surgical procedure. The primary objective was to determine the safety and efficacy of RFID. The secondary objective was to assess the impact of obesity and breast density on the RFID outcomes.

RESULTS: A total of 73 female patients met the eligibility criteria with stage I (59%) and grade 1 (51%) breast cancer with mean age of at diagnosis of 66.8 years and mean body mass index of 31.4 kg/m2. Patients had invasive ductal carcinoma (61%), hormonal positive (56%), and human epidermal growth factor receptor 2 negative (68%) disease. All RFID tags were placed under image guidance with 100% accuracy of placement with no evidence of migration or procedure revision. Ninety percent of patients had free surgical margins and only seven patients needed margin re-excision with successful removal of the lesion and the tag.

CONCLUSION: RFID localization technique is a safe, effective and reliable procedure that results in favorable patient outcomes and quality of life.}, } @article {pmid38185614, year = {2024}, author = {Leung, D and Castellani, D and Nicoletti, R and Dilme, RV and Sierra, JM and Serni, S and Franzese, C and Chiacchio, G and Galosi, AB and Mazzucchelli, R and Palagonia, E and Dell'Oglio, P and Galfano, A and Bocciardi, AM and Zhao, X and Ng, CF and Lee, HY and Sakamoto, S and Vasdev, N and Rivas, JG and Campi, R and Teoh, JY}, title = {The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.}, journal = {European urology oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euo.2023.12.006}, pmid = {38185614}, issn = {2588-9311}, abstract = {BACKGROUND AND OBJECTIVE: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP.

METHODS: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed.

KEY FINDINGS AND LIMITATIONS: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up.

In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate.

PATIENT SUMMARY: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery.}, } @article {pmid38180699, year = {2024}, author = {Nakagawa, S and Miyashita, M and Maeda, I and Goda, A and Tada, H and Amari, M and Kojima, Y and Tsugawa, K and Ohi, Y and Sagara, Y and Sato, M and Ebata, A and Harada-Shoji, N and Suzuki, T and Nakanishi, M and Ohta, T and Ishida, T}, title = {Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {38180699}, issn = {1573-7217}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.

RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.

CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.}, } @article {pmid38177130, year = {2024}, author = {Krishnaswamy, D and Bontempi, D and Thiriveedhi, VK and Punzo, D and Clunie, D and Bridge, CP and Aerts, HJWL and Kikinis, R and Fedorov, A}, title = {Enrichment of lung cancer computed tomography collections with AI-derived annotations.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {25}, pmid = {38177130}, issn = {2052-4463}, support = {HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; HHSN261201500003l//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; T32EB025823-04//U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)/ ; }, abstract = {Public imaging datasets are critical for the development and evaluation of automated tools in cancer imaging. Unfortunately, many do not include annotations or image-derived features, complicating downstream analysis. Artificial intelligence-based annotation tools have been shown to achieve acceptable performance and can be used to automatically annotate large datasets. As part of the effort to enrich public data available within NCI Imaging Data Commons (IDC), here we introduce AI-generated annotations for two collections containing computed tomography images of the chest, NSCLC-Radiomics, and a subset of the National Lung Screening Trial. Using publicly available AI algorithms, we derived volumetric annotations of thoracic organs-at-risk, their corresponding radiomics features, and slice-level annotations of anatomical landmarks and regions. The resulting annotations are publicly available within IDC, where the DICOM format is used to harmonize the data and achieve FAIR (Findable, Accessible, Interoperable, Reusable) data principles. The annotations are accompanied by cloud-enabled notebooks demonstrating their use. This study reinforces the need for large, publicly accessible curated datasets and demonstrates how AI can aid in cancer imaging.}, } @article {pmid38170222, year = {2024}, author = {Li, QY and Guo, Q and Luo, WM and Luo, XY and Ji, YM and Xu, LQ and Guo, JL and Shi, RS and Li, F and Lin, CY and Zhang, J and Ke, D}, title = {Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.}, journal = {Aging}, volume = {15}, number = {}, pages = {}, doi = {10.18632/aging.205338}, pmid = {38170222}, issn = {1945-4589}, abstract = {OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.

METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.

RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.

CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.}, } @article {pmid38112318, year = {2024}, author = {Brings, S and Mier, W and Beijer, B and Kliemank, E and Herzig, S and Szendroedi, J and Nawroth, PP and Fleming, T}, title = {Non-cross-linking advanced glycation end products affect prohormone processing.}, journal = {The Biochemical journal}, volume = {481}, number = {1}, pages = {33-44}, doi = {10.1042/BCJ20230321}, pmid = {38112318}, issn = {1470-8728}, abstract = {Advanced glycation end products (AGEs) are non-enzymatic post-translational modifications of amino acids and are associated with diabetic complications. One proposed pathomechanism is the impaired processing of AGE-modified proteins or peptides including prohormones. Two approaches were applied to investigate whether substrate modification with AGEs affects the processing of substrates like prohormones to the active hormones. First, we employed solid-phase peptide synthesis to generate unmodified as well as AGE-modified protease substrates. Activity of proteases towards these substrates was quantified. Second, we tested the effect of AGE-modified proinsulin on the processing to insulin. Proteases showed the expected activity towards the unmodified peptide substrates containing arginine or lysine at the C-terminal cleavage site. Indeed, modification with Nε-carboxymethyllysine (CML) or methylglyoxal-hydroimidazolone 1 (MG-H1) affected all proteases tested. Cysteine cathepsins displayed a reduction in activity by ∼50% towards CML and MG-H1 modified substrates. The specific proteases trypsin, proprotein convertases subtilisin-kexins (PCSKs) type proteases, and carboxypeptidase E (CPE) were completely inactive towards modified substrates. Proinsulin incubation with methylglyoxal at physiological concentrations for 24 h resulted in the formation of MG-modified proinsulin. The formation of insulin was reduced by up to 80% in a concentration-dependent manner. Here, we demonstrate the inhibitory effect of substrate-AGE modifications on proteases. The finding that PCSKs and CPE, which are essential for prohormone processing, are inactive towards modified substrates could point to a yet unrecognized pathomechanism resulting from AGE modification relevant for the etiopathogenesis of diabetes and the development of obesity.}, } @article {pmid38157332, year = {2023}, author = {Shinohara, T and Asoda, T and Nakano, Y and Yamada, H and Fujimori, Y}, title = {Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e942208}, doi = {10.12659/AJCR.942208}, pmid = {38157332}, issn = {1941-5923}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/pathology ; Mastectomy ; *Down Syndrome/complications/surgery ; Biomarkers, Tumor ; *Carcinoma, Ductal/surgery ; Germ Cells/pathology ; BRCA2 Protein/genetics ; }, abstract = {BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.}, } @article {pmid38152369, year = {2023}, author = {Wang, Z and Hua, L and Liu, X and Chen, X and Xue, G}, title = {A hematological parameter-based model for distinguishing non-puerperal mastitis from invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1295656}, pmid = {38152369}, issn = {2234-943X}, abstract = {PURPOSE: Non-puerperal mastitis (NPM) accounts for approximately 4-5% of all benign breast lesions. Ultrasound is the preferred method for screening breast diseases; however, similarities in imaging results can make it challenging to distinguish NPM from invasive ductal carcinoma (IDC). Our objective was to identify convenient and objective hematological markers to distinguish NPM from IDC.

METHODS: We recruited 89 patients with NPM, 88 with IDC, and 86 with fibroadenoma (FA), and compared their laboratory data at the time of admission. LASSO regression, univariate logistic regression, and multivariate logistic regression were used to screen the parameters for construction of diagnostic models. Receiver operating characteristic curves, calibration curves, and decision curves were constructed to evaluate the accuracy of this model.

RESULTS: We found significant differences in routine laboratory data between patients with NPM and IDC, and these indicators were candidate biomarkers for distinguishing between the two diseases. Additionally, we evaluated the ability of some classic hematological markers reported in previous studies to differentiate between NPM and IDC, and the results showed that these indicators are not ideal biomarkers. Furthermore, through rigorous LASSO and logistic regression, we selected age, white blood cell count, and thrombin time to construct a differential diagnostic model that exhibited a high level of discrimination, with an area under the curve of 0.912 in the training set and with 0.851 in the validation set. Furthermore, using the same selection method, we constructed a differential diagnostic model for NPM and FA, which also demonstrated good performance with an area under the curve of 0.862 in the training set and with 0.854 in the validation set. Both of these two models achieved AUCs higher than the AUCs of models built using machine learning methods such as random forest, decision tree, and SVM in both the training and validation sets.

CONCLUSION: Certain laboratory parameters on admission differed significantly between the NPM and IDC groups, and the constructed model was designated as a differential diagnostic marker. Our analysis showed that it has acceptable efficiency in distinguishing NPM from IDC and may be employed as an auxiliary diagnostic tool.}, } @article {pmid38151327, year = {2023}, author = {Kos, Z and Nielsen, TO and Laenkholm, AV}, title = {Breast Cancer Histopathology in the Age of Molecular Oncology.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a041647}, pmid = {38151327}, issn = {2157-1422}, abstract = {For more than a century, microscopic histology has been the cornerstone for cancer diagnosis, and breast carcinoma is no exception. In recent years, clinical biomarkers, gene expression profiles, and other molecular tests have shown increasing utility for identifying the key biological features that guide prognosis and treatment of breast cancer. Indeed, the most common histologic pattern-invasive ductal carcinoma of no special type-provides relatively little guidance to management beyond triggering grading, biomarker testing, and clinical staging. However, many less common histologic patterns can be recognized by trained pathologists, which in many cases can be linked to characteristic biomarker and gene expression patterns, underlying mutations, prognosis, and therapy. Herein we describe more than a dozen such histomorphologic subtypes (including lobular, metaplastic, salivary analog, and several good prognosis special types of breast cancer) in the context of their molecular and clinical features.}, } @article {pmid38145712, year = {2023}, author = {Bessell, E and Markovic, TP and Caterson, ID and Hendy, C and Burk, J and Picone, T and Fuller, NR}, title = {Cost-effectiveness analysis of recruitment strategies in a large diabetes prevention trial conducted across two sites in Sydney, Australia.}, journal = {Contemporary clinical trials}, volume = {137}, number = {}, pages = {107421}, doi = {10.1016/j.cct.2023.107421}, pmid = {38145712}, issn = {1559-2030}, abstract = {BACKGROUND: Diabetes prevention trials require large samples and community-based recruitment, which can be protracted and expensive. We analysed the cost-effectiveness of recruitment strategies used in a randomised placebo-controlled supplement trial in adults with prediabetes and overweight or obesity conducted in Sydney, Australia.

METHODS: Recruitment strategies included advertising through local radio stations and newspapers, television news coverage, online advertising and editorials, advertising in and referral from primary care settings, university- and hospital-based advertising, and attending or hosting local events. For each strategy, the number of expressions of interest, screenings booked, and randomised participants were collated. The percentage contribution from each strategy, overall cost, and cost per participant were calculated.

RESULTS: Of 4498 expressions of interest, 551 (12%) were eligible for onsite screening and 401 (9%) were randomised. Recruitment costs totalled AU$218,501, averaging AU$545 per participant. The recruitment strategy was recorded for 49% who expressed interest in the trial, and for 75% randomised into the trial. From these data, advertising on local radio stations was the most cost-effective strategy, contributing 46% of participants at AU$286 per participant, then advertising in and referral from primary care settings (57 participants [19%], AU$1438 per participant). The least cost-effective strategy was television news coverage, which was not targeted to the Sydney-based audience, contributing only six participants (AU$10,000 per participant).

CONCLUSION: Radio advertising and recruitment through healthcare were the most effective recruitment strategies in this trial. Recruitment strategies should be location-specific and appropriate for the target population, prioritising low-effort high-yield strategies. Trial investigators should seek opportunities for free advertising.}, } @article {pmid38147544, year = {2024}, author = {Hasan-Aslih, S and Idan, O and Willer, R and Halperin, E}, title = {Disadvantaged group members are prouder of their group when using the language of the dominant group compared to their native language.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {1}, pages = {e2307736120}, doi = {10.1073/pnas.2307736120}, pmid = {38147544}, issn = {1091-6490}, support = {335607//EC | European Research Council (ERC)/ ; }, abstract = {In ethnically and linguistically diverse societies, disadvantaged groups often face pressures to acquire and speak the advantaged group's language to achieve social inclusion and economic mobility. This work investigates how using the advantaged group's language affects disadvantaged group members' in-group pride and collective self-esteem, relative to using their native language. Across six experimental studies involving Palestinian citizens of Israel (total N = 1,348), we test two competing hypotheses: Disadvantaged group members may experience greater in-group pride when using a) their native language, due to its emotional significance (the nativity hypothesis), or b) the language of the advantaged group, due to activation of habituated compensatory responses to dominance relations (the identity enhancement hypothesis). We found that respondents reported significantly higher in-group pride when responding to a Hebrew survey when compared to performing the same activity in Arabic (Studies 1a and 1b), regardless of whether the researchers administering the survey were identified as Jewish or Arab (Studies 2a and 2b). Study 3 replicated this effect while employing the "bogus pipeline" technique, suggesting the pride expression was authentic, not merely driven by social desirability. Finally, Study 4 (pre-registered) examined additional measures of positive regard for the in-group, finding that participants described their group more positively in an attribute selection task, and reported greater collective self-esteem, when surveyed in Hebrew, rather than in Arabic. Taken together, these findings suggest that language use influences disadvantaged group members' perceptions and feelings concerning their group when those languages are associated with relative position in an intergroup hierarchy.}, } @article {pmid38141236, year = {2023}, author = {Thai, JN and Sevrukov, AB and Ward, RC and Monticciolo, DL}, title = {Cryoablation Therapy for Early-Stage Breast Cancer: Evidence and Rationale.}, journal = {Journal of breast imaging}, volume = {5}, number = {6}, pages = {646-657}, doi = {10.1093/jbi/wbad064}, pmid = {38141236}, issn = {2631-6129}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; *Cryosurgery/adverse effects ; Treatment Outcome ; Mammography ; Mastectomy, Segmental ; }, abstract = {Recent advances in breast cancer research and treatment propel a paradigm shift toward less aggressive and less invasive treatment for some early-stage breast cancer. Select patients with small, low-risk tumors may benefit from a less aggressive approach with de-escalated local therapy. Cryoablation of breast cancer is an emerging nonsurgical treatment alternative to breast-conserving surgery. Advantages of cryoablation over surgery include the use of local anesthesia, faster recovery, improved cosmesis, and cost savings. Proper patient selection and meticulous technique are keys to achieving successful clinical outcomes. The best candidates for cryoablation have unifocal invasive ductal carcinoma tumors that are low grade, hormone receptor positive, and ≤1.5 cm in size. In this review, we outline the current evidence, patient selection criteria, procedural technique, pre- and postablation imaging, and the advantages and limitations of cryoablation therapy.}, } @article {pmid38131316, year = {2023}, author = {Özden, A and Dalgıç, B and Demir, M and Hazırolan, G and Uzun, Ö and Metan, G}, title = {Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/1120009X.2023.2296146}, pmid = {38131316}, issn = {1973-9478}, abstract = {It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.}, } @article {pmid38125060, year = {2023}, author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E}, title = {Effectiveness of lower limb rehabilitation protocol using mobile health on quality of life, functional strength, and functional capacity among knee osteoarthritis patients who are overweight and obese: A randomized-controlled trial.}, journal = {Archives of rheumatology}, volume = {38}, number = {4}, pages = {590-601}, pmid = {38125060}, issn = {2618-6500}, abstract = {OBJECTIVES: This study aims to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) using mobile health (mHealth) on quality of life (QoL), functional strength, and functional capacity among knee OA patients who were overweight and obese.

PATIENTS AND METHODS: Between August 2019 and November 2020, a total of 96 patients (42 males, 54 females; mean age; 52.9±4.8 years; range, 40 to 60 years) were randomized into either the rehabilitation group with mobile health (RGw-mHealth) receiving reminders by using mHealth to carry on the strengthening exercises of LLRP and instructions of daily care (IDC), the rehabilitation group without mobile health (RGwo-mHealth) following the strengthening exercises of LLRP and instructions of daily care (IDC) and control group (CG) only following the IDC for duration of 12 weeks. The reminders for using mHealth were provided two times a day for three days a week. Primary outcome measures were QoL assessed by the Western Ontario and McMaster Universities Osteoarthritis Index summary score, and functional strength by five-repetition sit-to-stand test. Secondary outcome measure was functional capacity assessed by the Gait Speed Test. The assessments of QoL, functional strength, and functional capacity were taken at baseline and post-test after 12 weeks of intervention.

RESULTS: After 12 weeks of intervention, the patients in all three groups had a statistically significant improvement in QoL within groups (p<0.05). Patients in the RGw-mHealth and RGwo-mHealth had a statistically significant improvement in functional strength and walking gait speed within groups (p<0.05). The pairwise between-group comparisons (Bonferroni post-hoc test) of the mean changes in QoL, functional strength, and functional capacity at post-test assessments revealed that patients in the RGw-mHealth had a statistically significant greater mean change in QoL, functional strength and functional capacity relative to both the RGwo-mHealth and CG (p<0.001).

CONCLUSION: The improvement in QoL, functional strength, and functional capacity was greater among patients in the RGw-mHealth compared to the RGwo-mHealth or CG.}, } @article {pmid38114301, year = {2023}, author = {Khazaeli, M and Maruthi, VK and See, S and Ondracek, T and Gerami, P}, title = {Melanocyte colonization and pigmentation of breast carcinoma: A case report.}, journal = {Journal of cutaneous pathology}, volume = {}, number = {}, pages = {}, doi = {10.1111/cup.14564}, pmid = {38114301}, issn = {1600-0560}, abstract = {Pigmented mammary Paget disease is a rare variant of mammary Paget disease that is often clinically misdiagnosed as a melanocytic lesion of the skin or nipple-areolar complex. Careful morphological assessment, along with the performance of adequate immunohistochemical stains, will help in achieving the right diagnosis and avoiding misdiagnosis of the entity as malignant melanoma. We report a rare case of pigmented mammary Paget disease with concomitant colonization of the underlying invasive ductal carcinoma by melanocytes mimicking melanoma.}, } @article {pmid37479781, year = {2023}, author = {Boyer, L and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Fond, G}, title = {Real-world effectiveness of long-acting injectable antipsychotic treatments in a nationwide cohort of 12,373 patients with schizophrenia-spectrum disorders.}, journal = {Molecular psychiatry}, volume = {28}, number = {9}, pages = {3709-3716}, pmid = {37479781}, issn = {1476-5578}, mesh = {Male ; Humans ; Female ; *Antipsychotic Agents/therapeutic use ; *Schizophrenia/drug therapy ; Risperidone/therapeutic use ; Paliperidone Palmitate/therapeutic use ; Aripiprazole ; Injections ; Administration, Oral ; }, abstract = {This mirror-image study aimed to evaluate the real-life effectiveness of long-acting injectable antipsychotics (LAI) in schizophrenia. Patients with schizophrenia initiating LAIs January 2015-December 2016 were enrolled from the French National Health Data System (SNDS). Standardized mean differences (SMD > 0.1 deemed clinically significant) were calculated for psychiatric healthcare resource utilization measures assessed one year before (during oral AP treatment) and one year after LAI initiation. LAI effectiveness was analyzed overall and by age group, gender and compliance to oral AP, defined as exposure to an AP for at least 80% of the year before LAI initiation. 12,373 patients were included. LAIs were more frequently initiated in men (58.1%), young (18-34 years, 42.0%) and non-compliant (63.7%) patients. LAI initiation was effective in reducing the number and duration of psychiatric hospitalizations and psychiatric emergency department (ED) admissions in non-compliant patients (SMD = -0.19, -0.26 and -0.12, respectively), but not in compliant patients. First-generation LAIs, paliperidone and aripiprazole LAIs reduced psychiatric hospitalizations (SMD = -0.20, -0.24, -0.21, respectively) and ED admissions (SMD = -0.15, -0.13, -0.15, respectively). No differences in effectiveness were found for age or gender. In compliant patients, only aripiprazole LAI reduced the number of psychiatric hospitalizations (SMD = -0.13). Risperidone and paliperidone LAIs increased hospitalization duration (SMD = 0.15 and 0.18, respectively). The prescription of LAIs (except risperidone) should be recommended in all non-compliant patients, even in women and patients aged 35 or older. The lower frequency of administration of LAIs than of oral APs may improve compliance and hence reduce the risk of relapse. Aripiprazole LAI may represent a treatment of choice for compliant patients that should be further investigated.}, } @article {pmid38104283, year = {2023}, author = {Maman, A and Senol, O}, title = {Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.}, journal = {Puerto Rico health sciences journal}, volume = {42}, number = {4}, pages = {276-282}, pmid = {38104283}, issn = {2373-6011}, abstract = {OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.

MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.

RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.

CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.}, } @article {pmid38100925, year = {2023}, author = {Li, HM and Huang, TY and Chang, TH and Wen, TN}, title = {Paget's disease of the nipple with underlying occult invasive carcinoma detected by magnetic resonance imaging and second-look ultrasound: Case report.}, journal = {International journal of surgery case reports}, volume = {114}, number = {}, pages = {109139}, doi = {10.1016/j.ijscr.2023.109139}, pmid = {38100925}, issn = {2210-2612}, abstract = {INTRODUCTION: Paget's disease of the nipple (PDN) is a rare and often misdiagnosed condition characterized by the infiltration of adenocarcinoma cells into the nipple epidermis. It poses substantial diagnostic and therapeutic challenges due to its similarity to benign dermatological conditions and its association with in situ or invasive carcinoma.

CASE PRESENTATION: This report details the case of a 47-year-old woman with persistent nipple itching, rash, and occasional bloody discharge. No abnormalities were seen on the mammogram and ultrasound scans; punch biopsy was performed to confirm PDN. A small lesion missed by other imaging methods was detected via breast magnetic resonance imaging (MRI). A second-look ultrasound with needle localization enabled precise surgery. The pathology report after breast-conserving surgery (BCS) revealed invasive ductal carcinoma with no metastasis in the sentinel lymph node biopsy.

DISCUSSION: PDN often mimics benign skin conditions, leading to delayed diagnosis. Furthermore, timely identification is crucial as PDN is frequently associated with underlying breast malignancies. Additional imaging, such as breast MRI, is essential for comprehensive evaluation, as it can reveal hidden lesions previously undetected by conventional mammography and ultrasound. A second-look ultrasound guided needle placement for tumor localization, enhancing surgical precision, aesthetics, and reducing patient harm. Surgical management, including mastectomy, BCS with radiotherapy, and oncoplastic surgery, offers suitable options without affecting recurrence or survival in selected patients.

CONCLUSION: This case emphasizes the importance of employing additional imaging tools, such as breast MRI and second-look ultrasound for the early detection and surgical management of PDN.}, } @article {pmid38098206, year = {2023}, author = {Li, J and Wu, Y and Tian, Z and Shu, L and Wu, S and Wu, Z}, title = {Application Value of Ultrasound Elastography Combined With Contrast-Enhanced Ultrasound (CEUS) Quantitative Analysis in Differentiation of Nodular Fibrocystic Changes of the Breast From Invasive Ductal Carcinoma.}, journal = {Ultrasonic imaging}, volume = {}, number = {}, pages = {1617346231217087}, doi = {10.1177/01617346231217087}, pmid = {38098206}, issn = {1096-0910}, abstract = {This study aimed to compare the value of ultrasound elastography combined with contrast-enhanced ultrasound (CEUS) quantitative analysis in the differentiation of nodular fibrocystic breast change (FBC) from breast invasive ductal carcinoma (BIDC). We selected 50 patients each with nodular FBC and BIDC, who were admitted to the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2021. Their ultrasonic elastic images and CEUS videos were collected, their ultrasound elastography scores and the ratio of strain rate (SR) of the lesions were determined, and the exported DICOM format videos of CEUS were quantitatively analyzed using VueBox software to obtain quantitative perfusion parameters. The differences between the ultrasound elastography score and SR while comparing nodular FBC and BIDC cases were statistically significant (p < .05). The sensitivity, specificity, and accuracy of ultrasound elastography scores in the differential diagnoses of nodular FBC and BIDC were 74%, 88%, and 81%, respectively. Additionally, the sensitivity, specificity, and accuracy of SR in the differential diagnosis of nodular FBC and BIDC were 94%, 78%, and 86%, respectively. Statistically significant differences were observed in the CEUS quantitative perfusion parameters PE, AUC (WiAUC, WoAUC, WiWoAUC), and WiPI in both nodular FBC and BIDC according to the VueBox software (p < .05). The sensitivity, specificity, and accuracy of CEUS quantitative analysis in the differential diagnoses of nodular FBC and BIDC were 66%, 82%, and 74%, respectively. Using the pathological findings as the gold standard, ROC curves were established, and the area under the curve (AUC) of the CEUS quantitative analysis, elasticity score, SR, and ultrasound elastography combined with CEUS quantitative analysis were 0.731, 0.838, and 0.892, as well as 0.945, respectively. Ultrasound elasticity scoring, SR and CEUS quantitative analysis have certain application value for differentiating nodular FBC cases from BIDC; however, ultrasound elasticity imaging combined with CEUS quantitative analysis can help in improving the differential diagnostic efficacy of nodular FBC cases from BIDC.}, } @article {pmid38097248, year = {2023}, author = {Yin, L and Yin, AH and Pu, CC}, title = {Clinical characteristics and prognosis of primary small cell carcinoma of the breast: a propensity score-matched, population-based study.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e073841}, doi = {10.1136/bmjopen-2023-073841}, pmid = {38097248}, issn = {2044-6055}, abstract = {OBJECTIVE: The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC).

DESIGN: A retrospective cohort study.

SETTING: Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016.

PARTICIPANTS: Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study.

MATERIALS AND METHODS: Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB.

RESULTS: Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system.

CONCLUSION: PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.}, } @article {pmid38093163, year = {2023}, author = {Yi, S and Zhang, C and Li, M and Qu, T and Wang, J}, title = {Machine learning and experiments identifies SPINK1 as a candidate diagnostic and prognostic biomarker for hepatocellular carcinoma.}, journal = {Discover. Oncology}, volume = {14}, number = {1}, pages = {231}, pmid = {38093163}, issn = {2730-6011}, abstract = {Machine learning techniques have been widely used in predicting disease prognosis, including cancer prognosis. One of the major challenges in cancer prognosis is to accurately classify cancer types and stages to optimize early screening and detection, and machine learning techniques have proven to be very useful in this regard. In this study, we aimed at identifying critical genes for diagnosis and outcomes of hepatocellular carcinoma (HCC) patients using machine learning. The HCC expression dataset was downloaded from GSE65372 datasets and TCGA datasets. Differentially expressed genes (DEGs) were identified between 39 HCC and 15 normal samples. For the purpose of locating potential biomarkers, the LASSO and the SVM-RFE assays were performed. The ssGSEA method was used to analyze the TCGA to determine whether there was an association between SPINK1 and tumor immune infiltrates. RT-PCR was applied to examine the expression of SPINK1 in HCC specimens and cells. A series of functional assays were applied to examine the function of SPINK1 knockdown on the proliferation of HCC cells. In this study, 103 DEGs were obtained. Based on LASSO and SVM-RFE analysis, we identified nine critical diagnostic genes, including C10orf113, SPINK1, CNTLN, NRG3, HIST1H2AI, GPRIN3, SCTR, C2orf40 and PITX1. Importantly, we confirmed SPINK1 as a prognostic gene in HCC. Multivariate analysis confirmed that SPINK1 was an independent prognostic factor for overall survivals of HCC patients. We also found that SPINK1 level was positively associated with Macrophages, B cells, TFH, T cells, Th2 cells, iDC, NK CD56bright cells, Th1 cells, aDC, while negatively associated with Tcm and Eosinophils. Finally, we demonstrated that SPINK1 expression was distinctly increased in HCC specimens and cells. Functionally, silence of SPINK1 distinctly suppressed the proliferation of HCC cells via regulating Wnt/β-catenin pathway. The evidence provided suggested that SPINK1 may possess oncogenic properties by inducing dysregulated immune infiltration in HCC. Additionally, SPINK1 was identified as a novel biomarker and therapeutic target for HCC.}, } @article {pmid38091153, year = {2023}, author = {Schwartz, CJ and Khorsandi, N and Blanco, A and Mukhtar, RA and Chen, YY and Krings, G}, title = {Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {38091153}, issn = {1573-7217}, abstract = {PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.

METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).

RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months).

CONCLUSION: Almost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.}, } @article {pmid38090235, year = {2023}, author = {Adedokun, KA and Oluogun, WA and Oyenike, MA and Imodoye, SO and Yunus, LA and Lasisi, SA and Bello, IO and Kamorudeen, RT and Adekola, SA}, title = {Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.}, journal = {Sultan Qaboos University medical journal}, volume = {23}, number = {4}, pages = {526-533}, doi = {10.18295/squmj.7.2023.044}, pmid = {38090235}, issn = {2075-0528}, abstract = {OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.

METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.

RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.

CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.}, } @article {pmid38089951, year = {2023}, author = {Tong, CW and Cohen-Hallaleh, R}, title = {Goldilocks Mastectomy: The Middle Road Option for Obese Breast Cancer Patients.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50362}, doi = {10.7759/cureus.50362}, pmid = {38089951}, issn = {2168-8184}, abstract = {Breast cancer is the predominant cancer affecting females in Australia. With the rising obesity rates, the number of obese breast cancer patients is also rising. Full complex breast reconstruction is known to carry significant risk of complications in obese patients, hence we sought to utilize Goldilocks mastectomy as an alternative middle-ground option between standard mastectomy and complex breast reconstruction. A 63-year-old obese female presented with left nipple inversion. Ultrasonography revealed a 9.7 mm dilated retroareolar duct within the left breast, indicating lobular carcinoma. Subsequent biopsy analysis revealed estrogen/progesterone receptor (ER/PR)-positive cancer with equivocal human epidermal growth factor receptor 2 (HER2) status and a Ki67 index of 10%. Concurrently, a discrete area of conspicuous breast tissue prominence displayed characteristics of invasive ductal carcinoma with similar receptor status but a reduced Ki67 index of less than 5%. Traditional breast reconstruction options were unfavorable due to obesity, prompting consideration of a tailored Goldilocks mastectomy. The procedure was uncomplicated, and follow-up assessments revealed commendable wound healing, alongside the restoration of symmetrical breast contours. Conclusion: This study highlights the significance of Goldilocks mastectomy as an invaluable technique in the comprehensive management of breast cancer, particularly for obese patients characterized by a body mass index (BMI) exceeding 35 and substantial medical comorbidities.}, } @article {pmid38083560, year = {2023}, author = {Cheng, C and Foxworthy, GE and Fridman, GY}, title = {A Cuff Lead for Delivering Ionic Direct Current (iDC) to Block Neural Activities of Sciatic Nerve.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2023}, number = {}, pages = {1-4}, doi = {10.1109/EMBC40787.2023.10340183}, pmid = {38083560}, issn = {2694-0604}, abstract = {Direct current (DC) applied extracellularly can block action potential (AP) propagation in a neuron. This suppression paradigm has been proposed as a possible treatment for blocking nociceptive pain. However, the application of DC is limited in duration due to the charge injection constraint imposed by the evolution of electrochemical reactions at the metal electrode. To prolong the application of DC, a microfluidic lead filled with conductive electrolyte can be used to separate the metal electrode from the target nerve. Here, we describe a tripolar nerve cuff lead fabricated with biocompatible silicone to block the APs in the rat sciatic nerve. This lead has a self-curling silicone membrane to wrap around sciatic nerve for secured mechanical attachment and electrical isolation between the nerve and the surrounding muscle. In-vivo testing showed that delivering 1.4mA DC via the cuff lead blocked the nerve activity and reduced the evoked compound action potential (eCAP) to 30% of its unblocked response.}, } @article {pmid38076316, year = {2023}, author = {Qureshi, A and Gollamudi, S and Qureshi, S and Sondhi, N and Nabi, S and Genato, R and Xiao, P and Asarian, A}, title = {The phenomenon of spontaneous tumor regression in breast cancer.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {12}, pages = {rjad651}, pmid = {38076316}, issn = {2042-8812}, abstract = {Spontaneous tumor regression is an increasingly prevalent phenomenon of partial or complete disappearance of primary tumor tissue or associated metastases in the absence of therapeutic intervention. Cases of spontaneous regression have been established in malignant tumors, such as testicular germ cell tumor, renal cell cancer, melanoma, basal cell carcinoma, neuroblastoma, colon cancer, breast cancer, as well as metastases. Breast cancer has increasingly been reported to have a higher rate of spontaneous regression than previously thought. Immunologic response is cited as the forefront of spontaneous regression phenomenon, with the focus on immunologic cell death. This report brings awareness to a case of spontaneous regression observed in invasive ductal carcinoma of the breast and how disruption of the tumor microenvironment can take a variable course even in malignant disease.}, } @article {pmid38076287, year = {2023}, author = {Tractenberg, RE and Groah, SL and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH}, title = {Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {3}, pages = {31-43}, pmid = {38076287}, issn = {1945-5763}, abstract = {OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.

METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").

RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.

CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.}, } @article {pmid38075206, year = {2024}, author = {Sakurai, K and Yamada, S and Ito, R and Ochiai, M and Ando, T and Sakai, Y and Kato, T and Ito, H}, title = {Chromogenic in situ hybridization reveals specific expression pattern of long non-coding RNA DRAIC in formalin-fixed paraffin-embedded specimen.}, journal = {Non-coding RNA research}, volume = {9}, number = {1}, pages = {76-83}, pmid = {38075206}, issn = {2468-0540}, abstract = {Long non-coding RNA (lncRNA) plays an important role in the regulation of gene expression in normal and cancer cells. We previously discovered a novel tumor-suppressive lncRNA, DRAIC, in prostate cancer cells. Subsequent studies have demonstrated that DRAIC is dysregulated in various malignancies and exhibits a tumor-suppressive or pro-oncogenic function. However, details regarding its expression pattern in normal and cancerous tissues remain largely unknown. In this study, we performed chromogenic in situ hybridization (CISH) using RNAscope technology to assess DRAIC expression in formalin-fixed paraffin-embedded (FFPE) specimens. In the neuroendocrine-differentiated cancer cell line VMRC-LCD, CISH revealed a diffuse localization of DRAIC in the cytoplasm as well as specific accumulation in the nuclear compartment. DRAIC expression was comprehensively analyzed using tissue microarrays containing 89 normal and 155 tumor tissue samples. DRAIC was weakly expressed in normal epithelial cells of the colon, bronchiole, kidney, prostate, and testis. Conversely, DRAIC was moderately to highly expressed in some cancer tissues, including prostate adenocarcinoma, invasive ductal carcinoma of the breast, neuroendocrine carcinoma of the esophagus, lung adenocarcinoma, and small cell lung carcinoma. While DRAIC knockdown did not affect VMRC-LCD cellular viability and invasive ability, gene expression related to the neuroendocrine and cancer-related pathways was altered. Our expression analysis revealed the specific expression pattern of DRAIC in normal and cancerous FFPE tissues. The results presented here may lead to the elucidation of additional novel functions of DRAIC.}, } @article {pmid38071886, year = {2023}, author = {Ismail, Y and Zakaria, AS and Allam, R and Götte, M and Ibrahim, SA and Hassan, H}, title = {Compartmental Syndecan-1 (CD138) expression as a novel prognostic marker in triple-negative metaplastic breast cancer.}, journal = {Pathology, research and practice}, volume = {253}, number = {}, pages = {154994}, doi = {10.1016/j.prp.2023.154994}, pmid = {38071886}, issn = {1618-0631}, abstract = {BACKGROUND: Metaplastic breast cancer (MpBC) is rare, aggressive, and mostly triple-negative (TN) subtype of BC. We aimed to investigate the potential prognostic significance of Syndecan-1 (SDC1/CD138) expression in this unique tumor.

METHODS: Archived charts of 50 TNBC patients [21 MpBC and 29 invasive ductal carcinoma (IDC)] were retrospectively evaluated. Corresponding paraffin blocks were used for immunohistochemical (IHC) staining of SDC1. Compartmental (epithelial membranous, stromal, and cytoplasmic) staining scores were expressed in quartiles (Q) and correlated with disease-free survival (DFS) and overall survival (OS).

RESULTS: The median follow-up period was 54.6 months (range: 2.2-112.7). MpBC patients showed significantly worse DFS and OS than IDC (p = 0.007 and 0.004, respectively). MpBC demonstrated significantly higher Q4 stromal and membranous SDC1 compared to IDC (p = 0.016 and 0.021, respectively), whereas IDC exhibited significantly higher cytoplasmic Q4 SDC1 than MpBC (p = 0.015). Stromal Q4 SDC1 expression was found to be an independent factor associated with MpBC relative to IDC (OR: 6.7, 95% CI: 1.24-36.90; p = 0.028). Stromal Q4 SDC1 expression was also an independent prognostic parameter for worse DFS and OS compared to Q1-3 in the whole cohort (HR: 4.2, 95% CI: 1.6-10.5; p = 0.003 and HR: 5.8; 95% CI: 2.2-15.3; p < 0.001, respectively). In MpBC, cytoplasmic Q1-3 SDC1 expression was an independent prognostic indicator for worse OS compared with their IDC counterparts (HR: 2.837, 95% CI: 1.048-7.682; p = 0.04).

CONCLUSION: This study suggests, for the first time, that differential expression and localization of SDC1 may contribute to the pathogenesis and prognosis of TN-MpBC. Therefore, targeting SDC1 (CD138) could emerge as a novel therapeutic approach for this devastating disease.}, } @article {pmid38070191, year = {2023}, author = {Mouabbi, JA and Qaio, W and Shen, Y and Raghavendra, AS and Tripathy, D and Layman, RM}, title = {Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.}, journal = {The oncologist}, volume = {}, number = {}, pages = {}, doi = {10.1093/oncolo/oyad317}, pmid = {38070191}, issn = {1549-490X}, support = {MIRA RP170067//Cancer Prevention and Research Institute of Texas/ ; //NIH/ ; //NCI/ ; }, abstract = {BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.

RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001).

CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.}, } @article {pmid38067216, year = {2023}, author = {Bernhardt, M and Kristiansen, G}, title = {Molecular Alterations in Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {15}, number = {23}, pages = {}, doi = {10.3390/cancers15235512}, pmid = {38067216}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.}, } @article {pmid38065742, year = {2023}, author = {Su, H and Lin, X and Huo, J and Zhang, F}, title = {Multiple distant metastases after surgery for invasive ductal carcinoma of the parotid gland with ductal carcinoma in situ: A case report.}, journal = {Asian journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.asjsur.2023.11.140}, pmid = {38065742}, issn = {0219-3108}, } @article {pmid38059175, year = {2023}, author = {Zhou, S and Wang, J and Li, M and Yang, Y and Zhang, H and Chen, D}, title = {Bilateral and synchronous male breast cancer: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {16}, number = {11}, pages = {352-356}, pmid = {38059175}, issn = {1936-2625}, abstract = {Genetic mutational characterization of synchronous bilateral male breast cancer (BC) has been poorly reported due to its rarity. Herein, we present a 55-year-old male patient who was diagnosed with bilateral breast cancer (BBC) and harbored different gene mutations. The diagnosis of synchronous bilateral breast cancer (SBBC) was made using ultrasonography, magnetic resonance imaging (MRI), mammography and core-needle biopsy. Subsequently, bilateral modified radical mastectomies were performed, and histopathologic examination revealed invasive ductal carcinoma. To further investigate the genetic profile of the patient, the biopsy tissue from both breasts and a blood sample were subjected to targeted next generation sequencing (NGS). The genomic profile of the left breast (LB) sample revealed two copy number variations (CNVs), amplification of MCL1 and DAXX, while the right breast (RB) sample showed no obvious mutation. We are reporting this case along with its clinicopathologic findings and genetic investigations, since SBBS occurs extremely rarely, especially in men. The heterogeneity in gene mutations observed in this case may suggest a different pathogenesis and the need for different therapy strategies.}, } @article {pmid37776183, year = {2023}, author = {Liraz Zaltsman, S and Sharabi, S and Guez, D and Daniels, D and Cooper, I and Shemesh, C and Atrakchi, D and Ravid, O and Omesi, L and Rand, D and Livny, A and Schnaider Beeri, M and Friedman-Levi, Y and Shohami, E and Mardor, Y and Last, D}, title = {Application of Delayed Contrast Extravasation Magnetic Resonance Imaging for Depicting Subtle Blood-Brain Barrier Disruption in a Traumatic Brain Injury Model.}, journal = {Journal of neurotrauma}, volume = {}, number = {}, pages = {}, doi = {10.1089/neu.2023.0048}, pmid = {37776183}, issn = {1557-9042}, abstract = {The blood-brain barrier (BBB) is composed of brain microvasculature that provides selective transport of solutes from the systemic circulation into the central nervous system to protect the brain and spinal microenvironment. Damage to the BBB in the acute phase after traumatic brain injury (TBI) is recognized as a major underlying mechanism leading to secondary long-term damage. Because of the lack of technological ability to detect subtle BBB disruption (BBBd) in the chronic phase, however, the presence of chronic BBBd is disputable. Thus, the dynamics and course of long-term BBBd post-TBI remains elusive. Thirty C57BL/6 male mice subjected to TBI using our weight drop closed head injury model and 19 naïve controls were scanned by magnetic resonance imaging (MRI) up to 540 days after injury. The BBB maps were calculated from delayed contrast extravasation MRI (DCM) with high spatial resolution and high sensitivity to subtle BBBd, enabling depiction and quantification of BBB permeability. At each time point, 2-6 animals were sacrificed and their brains were extracted, sectioned, and stained for BBB biomarkers including: blood microvessel coverage by astrocyte using GFAP, AQP4, ZO-1 gaps, and IgG leakage. We found that DCM provided depiction of subtle yet significant BBBd up to 1.5 years after TBI, with significantly higher sensitivity than standard contrast-enhanced T1-weighted and T2-weighted MRI (BBBd volumes main effect DCM/T1/T2 p < 0.0001 F(2,70) = 107.3, time point p < 0.0001 F(2,133, 18.66) = 23.53). In 33% of the cases, both in the acute and chronic stages, there was no detectable enhancement on standard T1-MRI, nor detectable hyperintensities on T2-MRI, whereas DCM showed significant BBBd volumes. The BBBd values of TBI mice at the chronic stage were found significantly higher compared with age matched naïve animals at 30, 60, and 540 days. The calculated BBB maps were histologically validated by determining significant correlation between the calculated levels of disruption and a diverse set of histopathological parameters obtained from different brain regions, presenting different components of the BBB. Cumulative evidence from recent years points to BBBd as a central component of the pathophysiology of TBI. Therefore, it is expected that routine use of highly sensitive non-invasive techniques to measure BBBd, such as DCM with advanced analysis methods, may enhance our understanding of the changes in BBB function after TBI. Application of the DCM technology to other CNS disorders, as well as to normal aging, may shed light on the involvement of chronic subtle BBBd in these conditions.}, } @article {pmid38049608, year = {2023}, author = {Maggi, G and Giacobbe, C and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {}, number = {}, pages = {}, pmid = {38049608}, issn = {1531-135X}, abstract = {BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).

METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.

RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.

CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.}, } @article {pmid38047107, year = {2023}, author = {Zhang, W and Nowotny, H and Theodoropoulou, M and Simon, J and Hemmer, CM and Bidlingmaier, M and Auer, MK and Reincke, M and Uhlenhaut, H and Reisch, N}, title = {E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1249863}, pmid = {38047107}, issn = {1664-2392}, abstract = {PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.

METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.

RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.

CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.}, } @article {pmid38046940, year = {2023}, author = {van Veen, FEE and Scheepe, JR and Blok, BFM}, title = {Regional variation in urinary catheter use in the Netherlands from 2012 to 2021: a population-based cohort.}, journal = {Therapeutic advances in urology}, volume = {15}, number = {}, pages = {17562872231215181}, pmid = {38046940}, issn = {1756-2872}, abstract = {OBJECTIVES: Our aim was to evaluate trends and regional differences in the use of indwelling and intermittent urinary catheters in the community setting in the Netherlands from 2012 to 2021.

DESIGN AND METHODS: For this population-based cohort study, data on catheter use was collected from the Drug and Medical Devices Information System of the National Healthcare Institute of the Netherlands. This database contains information on the Dutch insured population, which was 100% of the total population in 2018. Users were divided into 12 provinces according to the Nomenclature of Territorial Units for Statistics codes. The number of catheter users was adjusted for the total population of the provinces by sex and age, and was expressed by users per 100,000 people. Negative binomial regression (NBR) was used to test for differences in clean intermittent catheter (CIC) and indwelling catheter (IDC) users across Dutch provinces.

RESULTS: Between 2012 and 2021, IDC users increased by 44.6% from 41,619 to 60,172, and CIC users increased by 27.3% from 34,204 to 43,528. The greatest increases were mainly observed among IDC users over 85 years old and male CIC users over 65 years old. NBR showed significant differences for IDC and CIC users between the 12 provinces. CIC incidence was higher in Drenthe and Groningen (Northern Netherlands) compared to Zuid-Holland (Southern Netherlands). IDC incidence was higher in seven provinces dispersed throughout the Netherlands compared to Noord-Holland.

CONCLUSION: CIC and IDC users have continued to increase in recent years; this was especially observed among older men. In addition, there were regional differences in the number of CIC and IDC users; CIC was more prominent in the northern region of the Netherlands, and IDC varied between multiple provinces. Practice variation in urinary catheterization may result from patient population differences or healthcare provider preferences and their alignment with guidelines.}, } @article {pmid38046902, year = {2023}, author = {Naeimzadeh, Y and Ilbeigi, S and Dastsooz, H and Rafiee Monjezi, M and Mansoori, Y and Tabei, SMB}, title = {Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {8236853}, pmid = {38046902}, issn = {2314-6141}, abstract = {Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.}, } @article {pmid38046195, year = {2023}, author = {Andrianto, A and Sudiana, IK and Suprabawati, DGA and Notobroto, HB}, title = {Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {841}, pmid = {38046195}, issn = {2046-1402}, abstract = {Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. Recurrence is still possible after mastectomy and chemotherapy and most often occurs in the first two years. We aimed to determine the mechanisms in early local recurrence in both types. Methods: We used an observational method with a cross-sectional study design. The samples were patients with early-stage IDC and ILC, who underwent modified radical mastectomy (MRM) and got adjuvant chemotherapy with taxan and anthracycline base, and experienced recurrence in the first two years after surgery. The materials in this study were paraffin blocks from surgical specimens; we examined vimentin, α-SMA and MMP1, PDGF and CD95 by immunohistochemistry (IHC). Data analysis was done using OpenEpi 3.0.1 and EZR. We used pathway analysis with linear regression. Results: There were 25 samples with local recurrence and 25 samples without recurrence in the ductal type group. The lobular type group consisted of six subjects without recurrence and seven with recurrence. There were significant differences in the expression of vimentin (p=0.000 and 0.021, respectively), PDGF (p=0.000 and 0.002) and CD95 (p=0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p=0.000) and α-SMA (p=0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: Local recurrence in early-stage IDC and ILC had different mechanisms. These findings are expected to make cancer treatment in both types more focused and efficient.}, } @article {pmid38028581, year = {2023}, author = {Tateishi, K and Kiyoi, M and Miyasaka, M and Kawaji, M and Nakanishi, H and Furuta, Y and Nishimatsu, M and Takahashi, Y and Nishikawa, M and Nishimura, Y}, title = {HER2-Positive Metaplastic Breast Cancer with Resistance to Neoadjuvant Chemotherapy: Case Report.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {1482-1488}, doi = {10.1159/000534847}, pmid = {38028581}, issn = {1662-6575}, abstract = {INTRODUCTION: Metaplastic breast carcinoma (MBC) is a rare histologic subtype of breast carcinoma, which is usually negative for estrogen receptor, progesterone receptor, and HER2. HER2-positive MBC is therefore extremely rare. Most MBCs have poor response to chemotherapy. HER2-targeted neoadjuvant chemotherapy (NAC) is widely performed and has high efficacy in treating HER2-positive breast cancer. We report an atypical case of HER2-positive breast cancer that had poor response to NAC and was diagnosed with MBC after the surgery.

CASE PRESENTATION: A 73-year-old woman noticed a mass in her right breast and visited our hospital. The mass was diagnosed as hormone receptor-negative, HER2-positive invasive ductal carcinoma, T2N0M0 stage IIA. She received HER2-targeted NAC comprising trastuzumab + pertuzumab + docetaxel. Despite three courses, we observed disease progression. The next NAC regimen was composed of two courses of epirubicin + cyclophosphamide, but the cancer continued to grow. She stopped receiving NAC and underwent a unilateral mastectomy and sentinel lymph node biopsy. Although the preoperative pathological result of core needle biopsy specimen showed invasive ductal carcinoma, the postoperative pathological result of the surgical specimen was MBC.

CONCLUSION: In this case, when the patient had undergone three courses of trastuzumab + pertuzumab + docetaxel, it would have been appropriate to review the result of the core needle biopsy with pathologists or to perform vacuum-assisted breast biopsy. This case suggests the importance of considering the possibility of special histologic subtypes such as MBC when a tumor with the diagnosis of invasive ductal carcinoma is resistant to NAC.}, } @article {pmid38027836, year = {2023}, author = {Gorelik, M and Szepsenwol, O and Doron, G}, title = {Promoting couples' resilience to relationship obsessive compulsive disorder (ROCD) symptoms using a CBT-based mobile application: A randomized controlled trial.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21673}, doi = {10.1016/j.heliyon.2023.e21673}, pmid = {38027836}, issn = {2405-8440}, abstract = {Relationship Obsessive Compulsive Disorder (ROCD) is a disabling form of obsessive-compulsive disorder (OCD) centering on interpersonal relationships. Previous findings suggest ROCD symptoms are particularly detrimental to romantic relationships. In this randomized controlled trial (RCT), we assessed influence a CBT-based mobile application used by both partners on resilience to ROCD symptoms, cognitions, and relationship dissatisfaction. The app consists of brief, daily exercises targeting OCD symptoms, related cognitions and attachment insecurities. Heterosexual couples (Ncouples = 103; Mage = 26.15) were randomly assigned to individually use a mobile application for 15 days (n = 49 couples) or to a control group (n = 54 couples). All participants completed questionnaires at baseline (T1), 15 days from baseline (T2), and 45 days from baseline (T3). All couples also underwent an ROCD resilience task at T2. Intention-to-treat analyses revealed that, in contrast to the control group, couples who used the app exhibited enhanced resilience in the resilience task, as well as measures of ROCD symptoms, cognitions, and relationship dissatisfaction. These observed effects persisted even at the 1-month follow-up. Concurrent use of brief mobile delivered cognitive training by both romantic partners may foster resilience in romantic couples.}, } @article {pmid38026906, year = {2023}, author = {Günay, S and Gökçek, B and Kandemir, Ö and Akan, A and Yalçın, O}, title = {Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.}, journal = {Turkish journal of surgery}, volume = {39}, number = {2}, pages = {115-120}, doi = {10.47717/turkjsurg.2023.5978}, pmid = {38026906}, issn = {2564-6850}, abstract = {OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.

MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).

RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.

CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.}, } @article {pmid38024932, year = {2023}, author = {Srivastava, NK and Singh, S and Mohanty, D and Hussain, N}, title = {Clinicopathological profile of breast cancer from Chhattisgarh India: A single-center hospital-based study.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {9}, pages = {1923-1930}, doi = {10.4103/jfmpc.jfmpc_2315_22}, pmid = {38024932}, issn = {2249-4863}, abstract = {BACKGROUND: Global breast cancer incidence is increasing at an annual rate of 3·1%. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%). However, the data from different parts of India are still lacking and the study was conducted to assess the burden of disease at tertiary referral centers in central India.

MATERIAL AND METHODS: Retrospective record analysis (June 2013-June 2017) of data from outdoor clinics and pathology reports. The patients aged <15 yrs, nonresidence of Chhattisgarh, and diagnosed outside the study period were excluded. The triple assessment was used to diagnose all breast lumps (sensitivity 99%).

RESULTS: Eighty patients were diagnosed having breast carcinoma. The mean age for breast cancer was 39 ± 3.028 years (ranged 31-50 years). Twenty patients had locally advanced breast carcinoma. The predominant religion was Hindu 55.00%. The referral pathway to seek medical care for breast cancer was via a gynecologist in 40% (32/80). Familial breast cancers were in 0.03% (3/80) of patients. None breast cancer patients have previous histology-proven benign breast disease. The mean size of the breast cancer lump was 3.56 cm (ranged 1.0-11.0 cm). Overlying skin ulceration (n = 2), skin infiltration/peau-d'- orange (n = 2), skin tethering (n = 4), and bloody nipple discharge were found in one patient. Breast cancer was diagnosed during lactation (postnatal period) in one patient. The maximum number of patients have tumor size >5 cm (72.6%). Immunohistochemistry and pathological analysis was done on core biopsy (n = 20) and surgical procedure (n = 60). Modified radical mastectomy was done in 52, breast conservative surgery with Sentinal Lymph node biopsy and axillary lymph node dissection in 6, and toilet mastectomy in two patients. The predominant tumors were solid (n = 79/80), with both solid and cystic types (1/80). The solid and cystic lesion on FNAC was of C3b type, and an excision biopsy revealed medullary carcinoma of the breast. Invasive ductal carcinoma-no special type (IDC-NST) was observed to be the most common histopathologic type (n = 70/80), followed by medullary carcinoma (n = 2), metaplastic carcinoma (n = 1), papillary carcinoma (n = 4), Paget disease with DCIS (n = 1), mucinous carcinoma (n = 1), invasive lobular carcinoma (n = 1). One male patient with breast cancer and two female patient having bilateral breast cancer also have IDC-NST.Scarff Bloom Richardson Grade was predominantly graded 2 in 46.25% (37/80) of breast cancer patients (Grade 1 = 9, Grade 2 = 37, Grade 3 = 34). Lymphovascular (LVI) and perineural invasion (PNI) were predominantly without LVI and PVI. (Lymphovascular present and perineural invasion present = 4, Lymphovascular present and perineural invasion absent = 32, Lymphovascular absent and perineural invasion absent = 42, Lymphovascular absent and perineural invasion present = 2). Histological examination of axillary lymph nodes showed the presence of malignant cells in all. Triple-negative breast carcinoma was 26.58% (21/79). Most breast cancer presented at stage II A = 37.5% (30/80) and II B = 28.7% (23/80) of the AJCC staging system.

CONCLUSION: The clinico-epidemio and histological profile of breast cancer in Chhattisgarh is similar to other parts of India. Scarff Bloom Richardson Grade was predominantly grade 2 in 46.25% (37/80) contrary to Grade III (70%) in other series from India.}, } @article {pmid38024052, year = {2023}, author = {Prabhu, SD and Rai, HS and Nayak, R and Naik, R and Jayasheelan, S}, title = {Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48557}, doi = {10.7759/cureus.48557}, pmid = {38024052}, issn = {2168-8184}, abstract = {BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.

OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.

METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.

RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.

CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.}, } @article {pmid38024024, year = {2023}, author = {Ishikawa, Y and Umezawa, R and Yamamoto, T and Takahashi, N and Takeda, K and Suzuki, Y and Kishida, K and Teramura, S and Ito, K and Jingu, K}, title = {Pre-treatment Evaluation of Patients Eligible for Whole Brain Radiation Therapy: The Risk of Hippocampal Metastases in a Retrospective Study of 248 Cases at a Single Institution.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49170}, doi = {10.7759/cureus.49170}, pmid = {38024024}, issn = {2168-8184}, abstract = {Whole brain radiation therapy (WBRT) is effective for multiple brain metastases (BMs) but may impair neurocognitive function (NCF). The incidence of hippocampal metastasis (HM) is low, and the factors associated with the occurrence of HM remain unclear. This study aimed to assess the occurrence of limbic system metastasis (LSM), including HM, and to analyze the risk of HM. We retrospectively analyzed 248 patients who underwent three-dimensional conformal radiation therapy for BMs between May 2008 and October 2015. Gadolinium-enhanced brain MRI or CT scans were used for diagnosis. Statistical analysis involved assessing clinical factors, including age, gender, primary tumor, number of BMs, and maximum metastasis diameter, in relation to the presence of HMs using logistic regression and receiver operating characteristic (ROC) curve analysis. The median age at treatment was 62 years (range: 11-83 years). Primary lesion sites included the lung (n = 150; 60.5%), breast (n = 45; 18.1%), gastrointestinal tract (n = 18; 7.3%), and bone and soft tissue (n = 2; 0.8%). Histological cancer types included adenocarcinoma (n = 113; 45.6%), squamous cell carcinoma (n = 26; 10.5%), small cell carcinoma (n = 28; 11.3%), invasive ductal carcinoma (n = 35; 14.1%), sarcoma (n = 3; 1.2%), and others (n = 43; 17.3%). MRI or CT scans of the 248 patients were analyzed, indicating a total count of 2,163 brain metastases (median: five metastases per patient). HMs were identified in 18 (7.3%) patients. The most common location for LSMs was the cingulum/cingulate gyrus in 26 (10.5%) patients. In univariate and multivariate analyses, patients with 15 or fewer BMs had a significantly lower incidence of HMs (odds ratio (OR), 0.018 (95% confidence interval (CI), 0.030-0.24)) (p < 0.0001). A maximal tumor size of less than 2 cm significantly increased the incidence of HMs (OR, 13.8 (95%CI, 1.80-105.3)) (p = 0.0003). The presence of cingulum/cingulate gyrus metastases also demonstrated a significant increase in the incidence of HMs (OR, 9.42 (95%CI, 3.30-26.84)) (p < 0.0001). The present study has uncovered a novel association between a high number of metastases in the cingulate gyrus and the development of HMs. Patients with BMs eligible for WBRT with metastases in the cingulate gyrus may be at risk of developing HM.}, } @article {pmid38022397, year = {2023}, author = {Zhu, XD and Yu, JH and Ai, FL and Wang, Y and Lv, W and Yu, GL and Cao, XK and Lin, J}, title = {Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.}, journal = {World journal of oncology}, volume = {14}, number = {6}, pages = {476-487}, doi = {10.14740/wjon1553}, pmid = {38022397}, issn = {1920-454X}, abstract = {BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.

METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.

RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.

CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.}, } @article {pmid38022128, year = {2023}, author = {Singh, I and Krasney, L and Civatte, W and Parrish, W}, title = {Treatment of Epiphyseal Metastasis to the Proximal Humerus Secondary to Breast Carcinoma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47564}, doi = {10.7759/cureus.47564}, pmid = {38022128}, issn = {2168-8184}, abstract = {Metastasis to the bone is a known risk of breast cancer, with the humerus being the most common upper extremity site of metastases, with most lesions located at the humeral diaphysis. We present a unique case of proximal humeral metastasis involving the epiphysis secondary to primary invasive ductal carcinoma in a middle-aged Caucasian female. It is important to have a high degree of suspicion for metastasis when musculoskeletal pain occurs in breast cancer patients, as it may be masked by common, degenerative conditions about the shoulder girdle. When humeral metastases involve the epiphysis, treatment options are complicated by its location, which jeopardizes the integrity of articular cartilage and the function of the shoulder girdle. External beam irradiation provides pain control in a non-invasive manner, sans surgical risks. Surgical intervention will vary depending on the characteristics of the bony lesion, but the use of endoprosthetics has emerged as the most effective option for restoring range of motion and pain control with acceptable rates of implant survival.}, } @article {pmid38020289, year = {2023}, author = {Koi, Y and Yamamoto, Y and Fukunaga, S and Kajitani, K and Ohara, M and Daimaru, Y and Tahara, H and Tamada, R}, title = {Assessment of the expression of microRNAs‑221‑3p, ‑146a‑5p, ‑16‑5p and BCL2 in oncocytic carcinoma of the breast: A case report.}, journal = {Oncology letters}, volume = {26}, number = {6}, pages = {535}, doi = {10.3892/ol.2023.14123}, pmid = {38020289}, issn = {1792-1082}, abstract = {Oncocytic carcinoma of the breast is rare and its molecular profiles remain poorly understood. MicroRNAs (miRNAs/miRs) have been identified as contributors to carcinogenesis at the post-transcriptional level; thus, an aberrant expression of miRNAs has attracted attention as a potential biomarker of numerous diseases, including cancer. The present study reports the case of a 76-year-old woman diagnosed with oncocytic carcinoma of the breast. Considering the distinctive feature of oncocytic carcinoma of the breast, which is the presence of granular eosinophilic cytoplasm containing numerous mitochondria, the present study hypothesized that the expression of mitochondria-related miRNAs could be altered in oncocytic carcinomas. Aberrant expression levels of the miRNAs previously reported as mitochondria-related miRNAs, such as miR-221-3p, -146a-5p and -16-5p, were revealed in tissue from specimens of oncocytic carcinoma of the breast, compared with that of a more typical type of invasive ductal carcinoma of the breast. The present study highlights the changes in miRNA expression in oncocytic carcinoma of the breast, suggesting its potential as a biomarker for diagnosis.}, } @article {pmid38019287, year = {2023}, author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Seebauer, L and Eldesouky, O and Aziz-Safaie, T and Hohmann, A and Herzig, S and Szendroedi, J and Nawroth, P and Heiland, S and Bendszus, M and Kurz, FT and Kopf, S and Jende, JME and Kender, Z}, title = {A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.}, journal = {Diabetologia}, volume = {}, number = {}, pages = {}, pmid = {38019287}, issn = {1432-0428}, support = {SFB 1158//Deutsche Forschungsgemeinschaft/ ; SFB1118//Deutsche Forschungsgemeinschaft/ ; }, abstract = {AIMS/HYPOTHESIS: Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.

METHODS: Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.

RESULTS: Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm[2]; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=-0.048 [95% CI -0.091, -0.006], p=0.027; SL B=-0.062 [95% CI -0.103, -0.020], p=0.004) and CSA (MH β=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=-0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio).

CONCLUSIONS/INTERPRETATION: The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03022721.}, } @article {pmid38012767, year = {2023}, author = {Deguchi, S and Iwakami, A and Tujigiwa, M and Otake, H and Mano, Y and Yamamoto, N and Nakazawa, Y and Misra, M and Nagai, N}, title = {Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.}, journal = {Journal of pharmaceutical health care and sciences}, volume = {9}, number = {1}, pages = {44}, pmid = {38012767}, issn = {2055-0294}, abstract = {BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).

METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.

RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.

CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.}, } @article {pmid38008819, year = {2023}, author = {Jalilian, E and Abolhasani-Zadeh, F and Afgar, A and Samoudi, A and Zeinalynezhad, H and Langroudi, L}, title = {Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20770}, pmid = {38008819}, issn = {2045-2322}, support = {IR.KMU.REC.1398.326//Kerman University of Medical Sciences/ ; }, abstract = {Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.}, } @article {pmid38007642, year = {2023}, author = {Zeng, YH and Yang, YP and Liu, LJ and Xie, J and Dai, HX and Zhou, HL and Huang, X and Huang, RL and Liu, EQ and Deng, YJ and Li, HJ and Wu, JJ and Zhang, GL and Liao, ML and Xu, XH}, title = {The discriminatory diagnostic value of multimodal ultrasound combined with blood cell analysis for granulomatous lobular mastitis and invasive ductal carcinoma of the breast.}, journal = {Clinical hemorheology and microcirculation}, volume = {}, number = {}, pages = {}, doi = {10.3233/CH-231999}, pmid = {38007642}, issn = {1875-8622}, abstract = {OBJECTIVE: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis(BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma(IDC) of the breast.

METHODS: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group(57 cases with 57 lesions) and the IDC group(100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic(ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval(CI), and the area under the curve(AUC) for patient age, lesion size, lesion resistive index(RI), and white blood cell(WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods.

RESULTS: There were statistically significant differences(P <  0.05) observed between GIM and IDC patients in terms of age, breast pain, the factors in Conventional US(lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS(contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA(white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15 cm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS(US-CEUS) was the highest(97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively.

CONCLUSION: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.}, } @article {pmid38007533, year = {2023}, author = {Wang, X and Zhou, L and Qi, L and Zhang, Y and Yin, H and Gan, Y and Gao, X and Cai, Y}, title = {High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.}, journal = {Prostate cancer and prostatic diseases}, volume = {}, number = {}, pages = {}, pmid = {38007533}, issn = {1476-5608}, support = {82273121//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2022JJ20096//Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation)/ ; }, abstract = {BACKGROUND: Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis, which were linked with discordant FDG positivity and low Prostate-Specific Membrane Antigen (PSMA) expression. A recent study only cited a DAC patient with low [68]Ga-PSMA-11 PET/CT uptake but high [18]F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients.

METHODS: The study was conducted on 87 DAC or/and IDC-P patients without any treatment and 97 PAC patients with a Gleason score ≥8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1.

RESULTS: PSMA expression in PAC was significantly higher than in DAC/IDC-P (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA expression between DAC/IDC-P and adjacent PAC (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P than in adjacent PAC (68.6 vs 51.3, p = 0.007), but was still lower than that in pure PAC (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in pure PAC (13.0 vs 6.6, p = 0.025), and in PAC adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001).

CONCLUSIONS: In DAC/IDC-P tissues, PSMA expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC/IDC-P may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism.}, } @article {pmid38007354, year = {2023}, author = {Miyajima, K and Sato, S and Uchida, N and Suzuki, H and Iwatani, K and Imai, Y and Aikawa, K and Yanagisawa, T and Kimura, S and Tashiro, K and Tsuzuki, S and Honda, M and Koike, Y and Miki, J and Miki, K and Shimomura, T and Yuen, S and Yamada, Y and Aoki, M and Takahashi, H and Urabe, F and Kimura, T}, title = {Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.}, journal = {Clinical genitourinary cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clgc.2023.10.005}, pmid = {38007354}, issn = {1938-0682}, abstract = {BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).

METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.

RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).

CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.}, } @article {pmid38001579, year = {2023}, author = {Surintrspanont, J and Zhou, M}, title = {Intraductal Carcinoma of the Prostate: To Grade or Not to Grade.}, journal = {Cancers}, volume = {15}, number = {22}, pages = {}, doi = {10.3390/cancers15225319}, pmid = {38001579}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a distinct tumor type characterized by an expansile growth of atypical glandular epithelial cells within pre-existing prostate glands and ducts and has significant implications on clinical outcomes and patient management. There is an agreement that isolated IDC-P should not be graded, and IDC-P should be reported with a comment on its clinical significance. However, whether IDC-P should be factored into Grade Group (GG) in the presence of concurrent prostate cancer (PCa) has been debated vigorously. The contradicting opinions were promulgated when the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathologists (ISUP) published their recommendations for this issue. When IDC-P is present with PCa, the ISUP recommends incorporating it in the GG for the entire case, whereas the GUPS recommends excluding it from the final GG. Consequently, pathologists and clinicians are faced with the conundrum of conflicting recommendations. In this review article, the authors evaluate the magnitude of discrepant GG between the two grading methods, explore the rationales behind the differing views of the two urological societies, present the current reporting practices for IDC-P, and propose a provisional and pragmatic guide to alleviate the dilemma of which recommendation to follow.}, } @article {pmid38000681, year = {2023}, author = {Boyraz, B and Ly, A}, title = {Spectrum of histopathologic findings in risk-reducing bilateral prophylactic mastectomy in patients with and without BRCA mutations.}, journal = {Human pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.humpath.2023.11.010}, pmid = {38000681}, issn = {1532-8392}, abstract = {Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.}, } @article {pmid37999984, year = {2023}, author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, SD and Gibbs, DL and Bridge, C and Herrmann, MD and Homeyer, A and Lewis, R and Aerts, HJWL and Krishnaswamy, D and Thiriveedhi, VK and Ciausu, C and Schacherer, DP and Bontempi, D and Pihl, T and Wagner, U and Farahani, K and Kim, E and Kikinis, R}, title = {National Cancer Institute Imaging Data Commons: Toward Transparency, Reproducibility, and Scalability in Imaging Artificial Intelligence.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {43}, number = {12}, pages = {e230180}, doi = {10.1148/rg.230180}, pmid = {37999984}, issn = {1527-1323}, abstract = {The remarkable advances of artificial intelligence (AI) technology are revolutionizing established approaches to the acquisition, interpretation, and analysis of biomedical imaging data. Development, validation, and continuous refinement of AI tools requires easy access to large high-quality annotated datasets, which are both representative and diverse. The National Cancer Institute (NCI) Imaging Data Commons (IDC) hosts large and diverse publicly available cancer image data collections. By harmonizing all data based on industry standards and colocalizing it with analysis and exploration resources, the IDC aims to facilitate the development, validation, and clinical translation of AI tools and address the well-documented challenges of establishing reproducible and transparent AI processing pipelines. Balanced use of established commercial products with open-source solutions, interconnected by standard interfaces, provides value and performance, while preserving sufficient agility to address the evolving needs of the research community. Emphasis on the development of tools, use cases to demonstrate the utility of uniform data representation, and cloud-based analysis aim to ease adoption and help define best practices. Integration with other data in the broader NCI Cancer Research Data Commons infrastructure opens opportunities for multiomics studies incorporating imaging data to further empower the research community to accelerate breakthroughs in cancer detection, diagnosis, and treatment. Published under a CC BY 4.0 license.}, } @article {pmid37999848, year = {2023}, author = {Tahir, S and Zahid, M and Hanif, MA and Javed, MY}, title = {g-C3N4/graphene oxide/SnFe2O4 ternary composite for the effective sunlight-driven photocatalytic degradation of methylene blue.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, pmid = {37999848}, issn = {1614-7499}, abstract = {A broadly used dye, methylene blue (MB), adversely impacts human health and water resources, which triggers efficient methods for its elimination. Semiconductor-based heterogeneous photocatalysis is an environmentally friendly approach that effectively degrades organic pollutants. The purpose of the current work is to elucidate and validate the application of a promising g-C3N4/GO/SnFe2O4 (CGS) composite for the environmental remediation of methylene blue dye. The ternary CGS composite has been synthesized using a solvothermal approach. The fabricated composites were analyzed through FTIR, XRD, SEM/EDX, UV-VIS spectroscopy, TEM, and XPS. The photoactivity of composites and affecting parameters (pH, H2O2 dosage, composite amount, initial dye concentration, and irradiation time) were observed in sunlight illumination. The optimal conditions for photocatalytic degradation were pH = 5, photocatalyst dosage = 30 mg/100 mL, H2O2 dosage = 6 mM, and initial dye concentration (IDC) of 10 ppm employing ternary CGS composite, and MB dye was degraded effectively within 1 h. Ninety-eight percent degradation efficacy was attained by employing ternary CGS composite under the optimized conditions. Scavenging analysis suggested that [•]OH radicals were the key reactive oxygen species (ROS) responsible for the photodegradation of MB dye. Furthermore, the CGS nanocomposite exhibited outstanding recyclability of 84% after five consecutive runs, demonstrating its potential for use in practical applications, particularly pollutant removal.}, } @article {pmid37996840, year = {2023}, author = {Yang, X and Tang, T and Zhou, T}, title = {Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {364}, pmid = {37996840}, issn = {1477-7819}, abstract = {BACKGROUND: Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC).

METHODS: We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups' disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS.

RESULTS: A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90-3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03-3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05-15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03-13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05-11.75, P = 0.04).

CONCLUSIONS: The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.}, } @article {pmid37995519, year = {2023}, author = {Antolín Novoa, S and Escrivá-de-Romaní, S and Tolosa Ortega, P and Oliva Fernández, L and López López, R and López González, A and de la Morena Barrio, P and Echavarria Díaz-Guardamino, I and Alés Martinez, JE and Garate, Z and González-Cortijo, L}, title = {Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100772}, doi = {10.1016/j.ctarc.2023.100772}, pmid = {37995519}, issn = {2468-2942}, abstract = {INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain.

MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients.

RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment.

CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.}, } @article {pmid37993928, year = {2023}, author = {Göker, M and Denys, H and Hendrix, A and De Wever, O and Van de Vijver, K and Braems, G}, title = {Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer.}, journal = {Breast cancer research : BCR}, volume = {25}, number = {1}, pages = {146}, pmid = {37993928}, issn = {1465-542X}, abstract = {PURPOSE: The aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC).

METHODS: Data of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001-2015, were analyzed.

RESULTS: ILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan-Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08-2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78-0.91), LVSI (hazard ratio 1.75, 95% CI 1.12-2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03-5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02-1.07), LVSI (hazard ratio 3.62, 95% CI 1.92-6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73-0.89).

CONCLUSION: The histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.}, } @article {pmid37993544, year = {2023}, author = {Voon, W and Hum, YC and Tee, YK and Yap, WS and Nisar, H and Mokayed, H and Gupta, N and Lai, KW}, title = {Evaluating the effectiveness of stain normalization techniques in automated grading of invasive ductal carcinoma histopathological images.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20518}, pmid = {37993544}, issn = {2045-2322}, support = {IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; IPSR/RMC/UTARRF/2022-C1/H01//Universiti Tunku Abdul Rahman Research Fund/ ; }, abstract = {Debates persist regarding the impact of Stain Normalization (SN) on recent breast cancer histopathological studies. While some studies propose no influence on classification outcomes, others argue for improvement. This study aims to assess the efficacy of SN in breast cancer histopathological classification, specifically focusing on Invasive Ductal Carcinoma (IDC) grading using Convolutional Neural Networks (CNNs). The null hypothesis asserts that SN has no effect on the accuracy of CNN-based IDC grading, while the alternative hypothesis suggests the contrary. We evaluated six SN techniques, with five templates selected as target images for the conventional SN techniques. We also utilized seven ImageNet pre-trained CNNs for IDC grading. The performance of models trained with and without SN was compared to discern the influence of SN on classification outcomes. The analysis unveiled a p-value of 0.11, indicating no statistically significant difference in Balanced Accuracy Scores between models trained with StainGAN-normalized images, achieving a score of 0.9196 (the best-performing SN technique), and models trained with non-normalized images, which scored 0.9308. As a result, we did not reject the null hypothesis, indicating that we found no evidence to support a significant discrepancy in effectiveness between stain-normalized and non-normalized datasets for IDC grading tasks. This study demonstrates that SN has a limited impact on IDC grading, challenging the assumption of performance enhancement through SN.}, } @article {pmid37993256, year = {2023}, author = {Wang, H and Ma, X and Li, S and Ni, X}, title = {SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.}, journal = {Aging}, volume = {15}, number = {}, pages = {}, doi = {10.18632/aging.205227}, pmid = {37993256}, issn = {1945-4589}, abstract = {BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.

METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.

RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.

CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.}, } @article {pmid37992687, year = {2023}, author = {d'Aquino, AI and Maikawa, CL and Nguyen, LT and Lu, K and Hall, IA and Jons, CK and Kasse, CM and Yan, J and Prossnitz, AN and Chang, E and Baker, SW and Hovgaard, L and Steensgaard, DB and Andersen, HB and Simonsen, L and Appel, EA}, title = {Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management.}, journal = {Cell reports. Medicine}, volume = {4}, number = {11}, pages = {101292}, doi = {10.1016/j.xcrm.2023.101292}, pmid = {37992687}, issn = {2666-3791}, abstract = {Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.}, } @article {pmid37991026, year = {2023}, author = {Su, HZ and Huang, M and Li, ZY and Tu, JH and Hong, LC and Zhang, ZB and Zhang, XD}, title = {Ultrasound characteristics of breast fibromatosis mimicking carcinoma.}, journal = {Journal of clinical ultrasound : JCU}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcu.23613}, pmid = {37991026}, issn = {1097-0096}, support = {2022J011366//Natural Science Foundation of Fujian Province/ ; 3502Z20214ZD1010//Science and Technology Foundation of Xiamen, China/ ; }, abstract = {PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma.

METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed.

RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities.

CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.}, } @article {pmid37652705, year = {2023}, author = {Li, X and Stitt, D and Lanzino, G and Giannini, C and Dubey, D and Carabenciov, ID}, title = {Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.}, journal = {Neurology}, volume = {101}, number = {21}, pages = {979-980}, doi = {10.1212/WNL.0000000000207762}, pmid = {37652705}, issn = {1526-632X}, } @article {pmid37978324, year = {2023}, author = {Stead, Z and Capuano, R and Di Natale, C and Pain, A}, title = {The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20167}, pmid = {37978324}, issn = {2045-2322}, support = {BAS/1/1020-01-01//KAUST faculty baseline fund/ ; BAS/1/1020-01-01//KAUST faculty baseline fund/ ; Giunta Regionale n. G10795//Regione Lazio/ ; Giunta Regionale n. G10795//Regione Lazio/ ; }, abstract = {Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.}, } @article {pmid37973797, year = {2023}, author = {Abdallah, N and Marion, JM and Tauber, C and Carlier, T and Hatt, M and Chauvet, P}, title = {Enhancing histopathological image classification of invasive ductal carcinoma using hybrid harmonization techniques.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20014}, pmid = {37973797}, issn = {2045-2322}, abstract = {This study aims to develop a robust pipeline for classifying invasive ductal carcinomas and benign tumors in histopathological images, addressing variability within and between centers. We specifically tackle the challenge of detecting atypical data and variability between common clusters within the same database. Our feature engineering-based pipeline comprises a feature extraction step, followed by multiple harmonization techniques to rectify intra- and inter-center batch effects resulting from image acquisition variability and diverse patient clinical characteristics. These harmonization steps facilitate the construction of more robust and efficient models. We assess the proposed pipeline's performance on two public breast cancer databases, BreaKHIS and IDCDB, utilizing recall, precision, and accuracy metrics. Our pipeline outperforms recent models, achieving 90-95% accuracy in classifying benign and malignant tumors. We demonstrate the advantage of harmonization for classifying patches from different databases. Our top model scored 94.7% for IDCDB and 95.2% for BreaKHis, surpassing existing feature engineering-based models (92.1% for IDCDB and 87.7% for BreaKHIS) and attaining comparable performance to deep learning models. The proposed feature-engineering-based pipeline effectively classifies malignant and benign tumors while addressing variability within and between centers through the incorporation of various harmonization techniques. Our findings reveal that harmonizing variabilities between patches from different batches directly impacts the learning and testing performance of classification models. This pipeline has the potential to enhance breast cancer diagnosis and treatment and may be applicable to other diseases.}, } @article {pmid37970339, year = {2023}, author = {Qu, J and Li, C and Liu, M and Wang, Y and Sun, S and Feng, Z and Wu, F and Zhang, S and Zhao, X}, title = {A novel web-based prognostic nomogram and the features influencing the curative effect of chemotherapy and radiotherapy for Paget's disease with invasive ductal carcinoma.}, journal = {American journal of cancer research}, volume = {13}, number = {10}, pages = {4508-4530}, pmid = {37970339}, issn = {2156-6976}, abstract = {Paget's disease (PD) of the breast is a rare underlying malignant tumor. Approximately 50% to 60% of patients with mammary PD are concurrently diagnosed with invasive ductal carcinoma (PD-IDC), a condition associated with a worse prognosis than IDC without PD. Thus far, there has been a lack of an accurate and efficient prognostic model for PD-IDC, and the factors influencing the effectiveness of chemotherapy and radiotherapy for these patients remain unknown. In this study, we developed a web-based nomogram based on the data from the Surveillance Epidemiology and End Results (SEER) database. We subjected the model to a series of validation methods, including area under the curve (AUC) values, receiver operating characteristic curve (ROC) analysis, calibration curves, and decision curve analysis (DCA). Our results demonstrated that our model exhibited high discrimination, accuracy, and clinical applicability in predicting the overall survival (OS) of patients with PD-IDC (testing set: three- and five-year AUCs, 0.831 and 0.841, respectively). To further validate our nomogram, we used external data from both our institution and sister hospitals (external data: three- and five-year AUCs, 0.892 and 0.914, respectively). Multivariable Cox regression analysis identified several independent unfavorable prognostic factors for the OS of patients with PD-IDC, including increasing age, high grade, widowed status, higher T stages, and the presence of bone metastases. Furthermore, propensity score matching (PSM)-adjusted analysis was conducted, revealing that chemotherapy did not significantly improve the survival of patients with PD-IDC across molecular subtypes, except for those in the grade III/IV group, where it improved both OS and breast cancer-specific survival (BCSS). Additionally, our findings indicated that only patients with PD-IDC with T4 and N3 stages benefited from radiotherapy, leading to improvements in both OS and BCSS. In conclusion, we have comprehensively analyzed the clinical characteristics and prognosis of patients with PD-IDC, culminating in the development of a user-friendly web-based nomogram for predicting their survival. Our predictive model is not only highly accurate but also offers simplicity, making it accessible for healthcare providers and patients. Furthermore, our stratified analysis highlights that the pathological grade, rather than the molecular subtype, plays a pivotal role in determining the efficacy of chemotherapy in improving the prognosis for patients with PD-IDC, while radiotherapy confers survival benefits to patients with PD-IDC in T4 and N3 stages.}, } @article {pmid37969442, year = {2023}, author = {Bai, J and Li, Y and Cai, L}, title = {Clinical implications of forkhead box M1, cyclooxygenase-2, and glucose-regulated protein 78 in breast invasive ductal carcinoma.}, journal = {World journal of clinical cases}, volume = {11}, number = {30}, pages = {7284-7293}, doi = {10.12998/wjcc.v11.i30.7284}, pmid = {37969442}, issn = {2307-8960}, abstract = {BACKGROUND: Breast infiltrating ductal carcinoma (BIDC) represents the largest heterotypic tumor group, and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.

AIM: To analyze the expression profiles and clinical implications of forkhead box M1 (FOXM1), cyclooxygenase-2 (COX-2), and glucose-regulated protein 78 (GRP78) in BIDC.

METHODS: A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis. The peripheral blood FOXM1, COX-2, and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined. Additionally, we investigated the diagnostic value of FOXM1, COX-2, and GRP78 in patients with BIDC and their correlations with clinicopathological features. Furthermore, BIDC patients were followed for 1 year to identify factors influencing patient prognosis.

RESULTS: The levels of FOXM1, COX-2, and GRP78 were significantly higher in BIDC patients compared to healthy controls (P < 0.05), and a positive correlation was observed among them (P < 0.05). Receiver operating characteristic analysis demonstrated that FOXM1, COX-2, and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC (P < 0.05). Subsequently, we found significant differences in FOXM1, COX-2, and GRP78 levels among patients with different histological grades and metastasis statuses (with vs without) (P < 0.05). Cox analysis revealed that FOXM1, COX-2, GRP78, increased histological grade, and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC (P < 0.001).

CONCLUSION: FOXM1, COX-2, and GRP78 exhibit abnormally high expression in BIDC, promoting malignant tumor development and closely correlating with prognosis. These findings hold significant research implications for the future diagnosis and treatment of BIDC.}, } @article {pmid37957878, year = {2023}, author = {Zhang, Y and Xin, Y and Zhang, N and Hu, X and Peng, B and Zhang, S and Yuan, Y}, title = {Breast Edema of Early-stage Invasive Ductal Carcinoma: Correlation with Axillary Lymph Node Metastasis and Clinical-pathological Characteristics.}, journal = {Current medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115734056243245231024082647}, pmid = {37957878}, issn = {1573-4056}, abstract = {OBJECTIVE: This study aimed to evaluate the association of different patterns of breast edema and clinical-pathological features and axillary lymph node (ALN) status in early invasive ductal carcinoma (IDC) for simple and readily available assessment and to guide surgeons to perform sentinel lymph node biopsy for selected patients.

MATERIALS AND METHODS: This retrospective analysis involved 207 individuals with clinical T1-T2 stage IDC. The clinical-pathological features of the patients were compared with different breast edema and ALN statuses. Independent risk factors for ALN metastasis were verified using multivariate logistic regression analysis.

RESULTS: ALN metastasis was confirmed in 100 of 207 patients (48.3%) with early-stage IDC. Significant differences were found between different ALN states for tumour size, clinical T stage, and breast edema (P <0.05). The clinical T2 stage (odds ratio-1.882, p=0.043) and moderate to severe edema (odds ratio-10.869, p=0.004) were independent risk factors for ALN metastasis. Moreover, better prognostic factors, including smaller tumour size, lower Ki-67 index and histologic grade, luminal A subtype, and lower incidence of lymph node metastasis, were more frequently found in patients with no breast edema (p<0.05).

CONCLUSION: Breast edema can be considered a promising feature to improve the predictive performance of pathological ALN status in patients with early-stage breast cancer and thus may contribute to preoperative treatment planning.}, } @article {pmid37957665, year = {2023}, author = {G K, AV and Gogoi, G and Kachappilly, MC and Rangarajan, A and Pandya, HJ}, title = {Label-free multimodal electro-thermo-mechanical (ETM) phenotyping as a novel biomarker to differentiate between normal, benign, and cancerous breast biopsy tissues.}, journal = {Journal of biological engineering}, volume = {17}, number = {1}, pages = {68}, pmid = {37957665}, issn = {1754-1611}, support = {BIRAC SRISTI PMU-2020/001//Biotechnology Industry Research Assistance Council/ ; CRG/2019/004963//Science and Engineering Research Board/ ; CRG/2019/004963//Science and Engineering Research Board/ ; 17X(3)/Ad-hoc/81/2022-ITR//Indian Council of Medical Research/ ; 17X(3)/Ad-hoc/81/2022-ITR//Indian Council of Medical Research/ ; SP-DSTO-0019//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, abstract = {BACKGROUND: Technologies for quick and label-free diagnosis of malignancies from breast tissues have the potential to be a significant adjunct to routine diagnostics. The biophysical phenotypes of breast tissues, such as its electrical, thermal, and mechanical properties (ETM), have the potential to serve as novel markers to differentiate between normal, benign, and malignant tissue.

RESULTS: We report a system-of-biochips (SoB) integrated into a semi-automated mechatronic system that can characterize breast biopsy tissues using electro-thermo-mechanical sensing. The SoB, fabricated on silicon using microfabrication techniques, can measure the electrical impedance (Z), thermal conductivity (K), mechanical stiffness (k), and viscoelastic stress relaxation (%R) of the samples. The key sensing elements of the biochips include interdigitated electrodes, resistance temperature detectors, microheaters, and a micromachined diaphragm with piezoresistive bridges. Multi-modal ETM measurements performed on formalin-fixed tumour and adjacent normal breast biopsy samples from N = 14 subjects were able to differentiate between invasive ductal carcinoma (malignant), fibroadenoma (benign), and adjacent normal (healthy) tissues with a root mean square error of 0.2419 using a Gaussian process classifier. Carcinoma tissues were observed to have the highest mean impedance (110018.8 ± 20293.8 Ω) and stiffness (0.076 ± 0.009 kNm[-1]) and the lowest thermal conductivity (0.189 ± 0.019 Wm[-1] K[-1]) amongst the three groups, while the fibroadenoma samples had the highest percentage relaxation in normalized load (47.8 ± 5.12%).

CONCLUSIONS: The work presents a novel strategy to characterize the multi-modal biophysical phenotype of breast biopsy tissues to aid in cancer diagnosis from small-sized tumour samples. The methodology envisions to supplement the existing technology gap in the analysis of breast tissue samples in the pathology laboratories to aid the diagnostic workflow.}, } @article {pmid37950182, year = {2023}, author = {Haghpanah, S and Hosseini-Bensenjan, M and Ramzi, M and Khosravizadegan, Z and Rezaianzadeh, A}, title = {Investigating the trends of incidence rates of breast cancer in Southern Iran: a population based survey.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {589}, pmid = {37950182}, issn = {1472-6874}, abstract = {BACKGROUND: The overall incidence of breast cancer is different all over the world and even within a nation. The present study aims to investigate the stratum-specific incidence trends of breast cancer in southern Iran.

METHODS: In this retrospective cohort study, the data of Fars Population-Based Cancer Registry was used during 2001-2018. New cancer cases with ICD-O-3 codes C50.0 to C50.9 were categorized based on age group, morphology, and topography. Age-specific incidence rates of breast cancer were calculated during 2001-2018. Annual overall and truncated age-standardized incidence rates and their 95% Confidence Intervals (CIs) were also calculated. Afterward, the Annual Percentage Changes (APCs) of the age-specific and age-standardized incidence rates of breast cancer during 2001-2018 were calculated using Joinpoint regression software.

RESULTS: An increasing trend was observed in the incidence of breast cancer among women during 2001-2018 (APC of age-standardized incidence rates: 9.5 (95% CI: 7.5, 11.5)).However, the trend was increasing less during the recent years. The APC of age-standardized rates decreased from 15.03 (95% CI: 10.4, 19.8) in 2007 to 6.15(95% CI: 4.0, 8.4) in 2018. The most common morphology of breast cancer was invasive ductal carcinoma (77.3% in females and 75.1% in males) and its trend was similar to the general trend of different types of breast cancer. The most common site of breast cancer was the upper outer quadrant. Most breast cancer cases were female and males accounted for 2.45% of the cases. Among females, 40-55 was the most prevalent age group.

CONCLUSION: The incidence of breast cancer among women living in southern Iran showed an increasing trend from 2001 to 2018. However, the rate of increase exhibited a milder slope during the more recent years. Based on the higher prevalence of breast cancer in the 40-55 age group observed in the present study, it offers valuable insight into the potential reduction of the breast cancer screening age from 50 to 40 years for healthy Iranian women. However, before implementing such a policy change, it is crucial to conduct additional studies that specifically examine the cost-effectiveness, as well as the potential benefits and risks associated with this alteration.}, } @article {pmid37949797, year = {2023}, author = {Aguado, JM and Navarro, D and Montoto, C and Yébenes, M and de Castro-Orós, I}, title = {Incidence of refractory CMV infection with or without antiviral resistance in Spain: A systematic literature review.}, journal = {Transplantation reviews (Orlando, Fla.)}, volume = {}, number = {}, pages = {100804}, doi = {10.1016/j.trre.2023.100804}, pmid = {37949797}, issn = {1557-9816}, abstract = {INTRODUCTION: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.

METHODS: PubMed, EMBASE, Cochrane and MEDES were searched systematically for relevant articles. We included randomized controlled trials and observational studies published during the period from January 1990 to June 2021.

RESULTS: From 212 screened records, we selected 19 papers including 1973 transplant recipients. Refractory infection ranged from 3 to 10% in studies with SOT recipients. The incidence of CMV resistance ranged from 1% to 36% in these patients. The incidence of CMV refractory infection in HSCT recipients ranged from 11 to 50%, while values for resistant infection ranged from 0% to 21%.

CONCLUSION: The wide range of definitions and values observed does not allow us to establish the true incidence of refractory CMV infection with or without resistances in SOT and HSCT patients in Spain. This review highlights the gap between clinical practice and clinical trials' definitions which needed to be updated to be easier followed in current clinical practice.}, } @article {pmid37941541, year = {2023}, author = {Bhimani, F and McEvoy, M and Gupta, A and Pastoriza, J and Shihabi, A and Basavatia, A and Tomé, WA and Fox, J and Mehta, K and Feldman, S}, title = {Case Report: Bilateral targeted intraoperative radiotherapy: a safe and effective alternative for synchronous bilateral breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1276766}, pmid = {37941541}, issn = {2234-943X}, abstract = {BACKGROUND: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC.

CASE REPORTS: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up.

CONCLUSION: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.}, } @article {pmid37938845, year = {2023}, author = {Yoon, TI and Jeong, J and Lee, S and Ryu, JM and Lee, YJ and Lee, JY and Hwang, KT and Kim, H and Kim, S and Lee, SB and Ko, BS and Lee, JW and Son, BH and Metzger, O and Kim, HJ}, title = {Survival Outcomes in Premenopausal Patients With Invasive Lobular Carcinoma.}, journal = {JAMA network open}, volume = {6}, number = {11}, pages = {e2342270}, doi = {10.1001/jamanetworkopen.2023.42270}, pmid = {37938845}, issn = {2574-3805}, abstract = {IMPORTANCE: The disparate prognostic implications between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have been demonstrated. However, information on premenopausal patients remains insufficient.

OBJECTIVE: To examine long-term survival outcomes of ILC and IDC in premenopausal patients using national databases.

This cohort study used the Surveillance, Epidemiology, and End Results (SEER), Korean Breast Cancer Registry (KBCR), and Asan Medical Center Research (AMCR) databases to identify premenopausal patients with stage I to III ILC or IDC between January 1, 1990, and December 31, 2015. The median follow-up time was 90 (IQR, 40-151) months in the SEER database, 94 (IQR, 65-131) months in the KBCR database, and 120 (IQR, 86-164) months in the AMCR database. Data were analyzed from January 1 to May 31, 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was breast cancer-specific survival (BCSS), which was analyzed according to histological type, and the annual hazard rate was evaluated. Survival rates were analyzed using a log-rank test and a Cox proportional hazards regression model with time-varying coefficients. Multivariable analysis was performed by adjusting for tumor characteristics and treatment factors.

RESULTS: A total of 225 938 women diagnosed with IDC or ILC and younger than 50 years were identified. Mean (SD) age at diagnosis was 42.7 (5.3) years in the SEER database, 41.8 (5.5) years in the KBCR database, and 41.8 (5.5) years in the AMCR database. In terms of race (available for the SEER database only), 12.4% of patients were Black, 76.1% were White, 11.0% were of other race (including American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander), and 0.5% were of unknown race). Patients with ILC had better BCSS in the first 10 years after diagnosis than those with IDC (hazard ratios [HRs], 0.73 [95% CI, 0.68-0.78] in the SEER database, 1.20 [95% CI, 0.91-1.58] in the KBCR database, and 0.50 [95% CI, 0.29-0.86] in the AMCR database), although BCSS was worse after year 10 (HRs, 1.80 [95% CI, 1.59-2.02] in the SEER database, 2.79 [95% CI, 1.32-5.88] in the KBCR database, and 2.23 [95% CI, 1.04-4.79] in the AMCR database). Similar trends were observed for hormone receptor-positive tumors (HRs, 1.55 [95% CI, 1.37-1.75] in the SEER database, 2.27 [95% CI, 1.01-5.10] in the KBCR database, and 2.12 [95% CI, 0.98-4.60] in the AMCR database). Considering the annual hazard model of BCSS, IDC events tended to decline steadily after peaking 5 years before diagnosis. However, the annual peak event of BCSS was observed 5 years after diagnosis for ILC, which subsequently remained constant.

CONCLUSIONS AND RELEVANCE: These findings suggest that premenopausal women with ILC have worse BCSS estimates than those with IDC, which can be attributed to a higher late recurrence rate of ILC than that of IDC. Histological subtypes should be considered when determining the type and duration of endocrine therapy in premenopausal women.}, } @article {pmid37936612, year = {2023}, author = {Li, Y and Wei, XL and Pang, KK and Ni, PJ and Wu, M and Xiao, J and Zhang, LL and Zhang, FX}, title = {A comparative study on the features of breast sclerosing adenosis and invasive ductal carcinoma via ultrasound and establishment of a predictive nomogram.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1276524}, pmid = {37936612}, issn = {2234-943X}, abstract = {OBJECTIVE: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA.

MATERIALS AND METHODS: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed.

RESULT: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets.

CONCLUSION: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.}, } @article {pmid37933375, year = {2023}, author = {Mahoney, MT and Kubinak, N and Masi, A and Lok, C and Eanelli, TR}, title = {Mind the Gap: Recurrence of Oligometastatic Breast Invasive Ductal Carcinoma in the Sternal Gap of Two Tangential Photon Fields of Bilateral Whole Breast Irradiation a Decade Later.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e46601}, pmid = {37933375}, issn = {2168-8184}, abstract = {Despite bilateral breast cancer being a rare clinical entity compared to unilateral breast cancer, both share a treatment paradigm of breast-conserving therapy for limited disease and metastasis direct therapy for oligometastatic disease. We present a case of left breast invasive ductal carcinoma in the setting of original bilateral breast cancer, now with oligometastatic recurrence to the soft tissue of the sternum, notably in an area not previously irradiated, over a decade later.}, } @article {pmid37925055, year = {2023}, author = {Derakhshan, F and Da Cruz Paula, A and Selenica, P and da Silva, EM and Grabenstetter, A and Jalali, S and Gazzo, AM and Dopeso, H and Marra, A and Brown, DN and Ross, DS and Mandelker, D and Razavi, P and Chandarlapaty, S and Wen, HY and Brogi, E and Zhang, H and Weigelt, B and Pareja, F and Reis-Filho, JS}, title = {Non-Lobular Invasive Breast Carcinomas with Bi-Allelic Pathogenic CDH1 Somatic Alterations: a Histologic, Immunophenotypic and Genomic Characterization.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {}, number = {}, pages = {100375}, doi = {10.1016/j.modpat.2023.100375}, pmid = {37925055}, issn = {1530-0285}, abstract = {CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, bi-allelic CDH1 alterations may be found in non-lobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 bi-allelic genetic alterations. Analysis of 5,842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multi-gene panel was conducted to identify BCs with bi-allelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 bi-allelic genetic alterations were compared to those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Out of 896 CDH1-altered BCs, 889 samples were excluded based on diagnosis of invasive mixed ductal/lobular carcinoma or ILC or detection of monoallelic CDH1 alterations. Only 7 of 5,842 (0.11%) BCs harbored bi-allelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive and 2/7 (29%) were ER-negative/HER2-negative. 5/7 (71%) were of Nottingham grade 2 and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 bi-allelic genetic alterations included a mucinous carcinoma (n=1), IDCs with focal nested growth (n=2), IDC with solid papillary (n=1) or apocrine (n=2) features and an IDC of no special type (NST; n=1). E-cadherin expression as detected by immunohistochemistry was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). NL-BCs with CDH1 bi-allelic genetic alterations displayed recurrent genetic alterations including TP53, PIK3CA (57%, 4/7; each), FGFR1 and NCOR1 (28%, 2/7, each) alterations. As compared to CDH1-wildtype IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, p=0.03) but no significant differences were detected when compared to matched ILCs. NL-BCs with CDH1 bi-allelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.}, } @article {pmid37922498, year = {2023}, author = {Maggi, G and Giacobbe, C and Iannotta, F and Santangelo, G and Vitale, C}, title = {Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.}, journal = {European journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ene.16109}, pmid = {37922498}, issn = {1468-1331}, abstract = {BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.

METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.

RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.

CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.}, } @article {pmid37921670, year = {2023}, author = {Kalra, R and Lim, B and Ellis, MJ and Kavuri, SM}, title = {The uncharted role of HER2 mutant alleles in breast cancer.}, journal = {Oncotarget}, volume = {14}, number = {}, pages = {904-907}, doi = {10.18632/oncotarget.28489}, pmid = {37921670}, issn = {1949-2553}, abstract = {Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.}, } @article {pmid37920380, year = {2023}, author = {Alshaibani, N and Chandramohan, JK and Khairi, SS and Al-Hashimi, F and Aljawder, AA}, title = {Invasive Cystic Hypersecretory Ductal Carcinoma of Breast: Challenges in Diagnosis and Management.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {1259-1266}, pmid = {37920380}, issn = {1662-6575}, abstract = {Cystic hypersecretory lesions of the breast are a spectrum of conditions ranging from cystic hypersecretory hyperplasia with atypia and invasive cystic hypersecretory carcinoma (CHC). It is a subtype of ductal carcinoma of the breast. The tumour is very infrequent and hence, extensive literature is limited. This culminates in the fact that it does not feature as part of the WHO classification of breast tumours. However, a good knowledge about its distinct pathological features can avert misdiagnosis and help differentiate CHC from other conditions. Thus far, only 22 cases of invasive CHC have been reported, of which 3 were microinvasive. Only 7 cases of axillary lymph node metastasis have been documented. We report a case of invasive CHC of the breast that was metastatic to the axilla and refractory to neoadjuvant chemotherapy. Our case report aims to add to the literature on the disease, aiming to support large-scale studies in the future in order to elaborate on its clinical and biological characteristics.}, } @article {pmid37919558, year = {2023}, author = {Avatefi, M and HadavandSiri, F and Nazari, SSH and Akbari, ME}, title = {Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {}, number = {}, pages = {e1927}, doi = {10.1002/cnr2.1927}, pmid = {37919558}, issn = {2573-8348}, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.

AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.

METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC.

CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.}, } @article {pmid37914605, year = {2023}, author = {Shuman, E and Goldenberg, A and Saguy, T and Halperin, E and van Zomeren, M}, title = {When Are Social Protests Effective?.}, journal = {Trends in cognitive sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tics.2023.10.003}, pmid = {37914605}, issn = {1879-307X}, abstract = {Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.}, } @article {pmid37910521, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Marquez, M and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0287829}, doi = {10.1371/journal.pone.0287829}, pmid = {37910521}, issn = {1932-6203}, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, } @article {pmid37908910, year = {2023}, author = {Malik, M and Yasmin, S and Kumar, A and Hassan, Y and Rizvi, Y and Iffat, }, title = {Can Artificial Intelligence Beat Humans in Detecting Breast Malignancy on Mammograms?.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e46208}, pmid = {37908910}, issn = {2168-8184}, abstract = {BACKGROUND: The study was aimed at identifying how useful Computer-Aided Detection (CAD) could be in reducing false-negative reporting in mammography and early detection of breast cancer at an early stage as the best protection is early detection.

MATERIALS AND METHODS: This retrospective study was conducted in a tertiary care setup of Atomic Energy Cancer Hospital, Nuclear Medicine, Oncology and Radiotherapy Institute (AECH-NORI), where 33 patients with suspicious findings on mammography and subsequent biopsy-proven malignancy were included. The findings of mammography including the lesion type, breast parenchymal density, and sensitivity of CAD detection, as well as the final biopsy results, were recorded. A second group of 40 normal screening mammograms was also included who had no symptoms, had Breast Imaging-Reporting and Data System category I(BI-RADS I) mammograms, and had no pathology identified on correlative sonomammography as well.

RESULTS: A total of 35 masses, 11 pleomorphic clusters of microcalcification, five clustered foci of macrocalcification, and nine lesions with pleomorphic clusters of microcalcification and two with pleomorphic clusters of microcalcification only were included. The CAD system was able to identify 26 masses (74%), eight lesions with pleomorphic clusters of microcalcification (72%), five foci of macrocalcification (100%), six lesions with pleomorphic clusters of microcalcification (66%), and two pleomorphic clusters of microcalcification without formed mass (100%). The overall sensitivity of the CAD system was 75.8%. CAD was able to identify 13 out of 16 masses with invasive ductal carcinoma (81.3%), eight out of nine lesions proven as invasive ductal carcinoma with ductal carcinoma in situ (DCIS) (88.9%), two out of five masses with invasive lobular carcinoma (40%), four out of four masses with invasive mammary carcinoma (100%), and zero out of one lesion identified as medullary carcinoma (0%). There was 100% detection for pleomorphic clusters of microcalcification without formed mass with CAD marking two out of two mammograms.

CONCLUSION: CAD performed better with combined lesions, accurately marked pleomorphic clusters of microcalcification, and identified small lesions in predominant fibrofatty parenchymal density but was not reliable in dense breast, areas of asymmetric increased density, summation artifacts, edematous breast parenchyma, and retroareolar lesions. It also performed poorly with ill-defined lesions of invasive lobular carcinoma. Human intelligence hence beats CAD for the diagnosis of breast malignancy in mammograms as per our experience.}, } @article {pmid37900827, year = {2023}, author = {Heng, YJ and Zhang, KJ and Valero, MG and Baker, GM and Fein-Zachary, VJ and Irwig, MS and Wulf, GM}, title = {Invasive Ductal Carcinoma of the Breast in a Transgender Man: A Case Report.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {811-817}, pmid = {37900827}, issn = {1662-6575}, abstract = {There is limited literature about breast cancer in the transgender population. Very little is known about how gender-affirming hormone therapy affects their breast cancer risk. On the other end, for those diagnosed with breast cancer, there are no clinical guidelines to manage their breast cancer, specifically, how to manage their gender-affirming hormone therapy during breast cancer treatment. Here, we report a 52-year-old transman diagnosed with a grade 2 invasive ductal carcinoma (ER+/PR+/HER2-), and ductal carcinoma in situ (DCIS) of intermediate grade. We discussed his risk factors as well as treatment options.}, } @article {pmid37900789, year = {2023}, author = {Mostafa, S and Habib, MB and Ahmed, N and Sawaf, B and Sadik, N and Abdulhadi, AM}, title = {Large Ascites in a Cirrhotic Patient Reveal an Isolated and Late Metastasis of Ductal Breast Cancer: A Case Study.}, journal = {Case reports in oncology}, volume = {16}, number = {1}, pages = {585-590}, pmid = {37900789}, issn = {1662-6575}, abstract = {Breast cancer is the most prevalent cancer in women worldwide, and its prevalence has increased since the introduction of screening programs. Most cases are discovered at an early stage; however, despite effective treatment, some cases progress to metastasis. The most common breast cancer metastatic locations are the bone, liver, and lungs. Ascites malignant due to peritoneal involvement is a rare manifestation of metastatic breast cancer. After 8 years of well-controlled breast cancer, we report a 54-year-old woman who presents with malignant ascites and is known to have cirrhosis of the liver.}, } @article {pmid37897648, year = {2023}, author = {Zhao, YY and Ge, HJ and Yang, WT and Shao, ZM and Hao, S}, title = {Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {37897648}, issn = {1573-7217}, support = {82203789//National Natural Science Foundation of China/ ; 82102683//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.

RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.

CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.}, } @article {pmid37890687, year = {2023}, author = {Liao, H and Wang, H and Zheng, R and Yu, Y and Zhang, Y and Lv, L and Zhang, B and Chen, J}, title = {LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.}, journal = {Cellular signalling}, volume = {}, number = {}, pages = {110943}, doi = {10.1016/j.cellsig.2023.110943}, pmid = {37890687}, issn = {1873-3913}, abstract = {Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.}, } @article {pmid37879875, year = {2023}, author = {Wang, HY and Li, SJ and Zhang, AL and Ni, XC}, title = {[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {40}, pages = {3204-3210}, doi = {10.3760/cma.j.cn112137-20230531-00902}, pmid = {37879875}, issn = {0376-2491}, abstract = {Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.}, } @article {pmid37874803, year = {2023}, author = {Coskunpinar, E and Tiryakioglu, DZ and Abaci, N and Tukenmez, M and Pence, S}, title = {Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {11}, pages = {814-820}, doi = {10.4149/BLL_2023_125}, pmid = {37874803}, issn = {0006-9248}, abstract = {OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.

BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.

METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR.  Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing  IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.

CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).}, } @article {pmid37874736, year = {2023}, author = {Munro-Kramer, ML and Loder, C and Kalpakjian, C and Martin, KE and Hess, A and Smith, E and Parrish, D and Ernst, S}, title = {Creating a tool to understand university students' experiences regarding inappropriate, disrespectful, and coercive (IDC) healthcare interactions.}, journal = {Journal of American college health : J of ACH}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/07448481.2023.2272190}, pmid = {37874736}, issn = {1940-3208}, abstract = {Objective: The purpose of this study was to develop a survey tool to capture inappropriate, disrespectful, and coercive (IDC) interactions with healthcare providers among a diverse sample of university students. Participants: Participants were university students at one large Midwestern public university. Methods: An exploratory qualitative approach was used to create a survey tool to capture IDC interactions. Results: In Phase I, 9 focus group discussions (FGDs) and 3 individual interviews were conducted with a total of 38 participants. In Phase II, 18 participants completed cognitive interviews. Themes across all FGDs included: (1) communication; (2) respect for identity; (3) institutional practices; (4) power imbalances; and (5) lack of patient education and empowerment. Queer participants discussed unique considerations of how queer identity influences one's IDC healthcare experiences. Conclusions: This study resulted in the development of a 64-70 item tool, the IDC Survey, to measure the prevalence and characteristics of IDC healthcare interactions.}, } @article {pmid37873952, year = {2023}, author = {Patel, K and Rao, DM and Sundersingh, S and Velusami, S and Rajkumar, T and Nair, B and Pandey, A and Chatterjee, A and Mani, S and Gowda, H}, title = {MicroRNA Expression Profile in Early-Stage Breast Cancers.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {}, number = {}, pages = {}, doi = {10.2174/0122115366256479231003064842}, pmid = {37873952}, issn = {2211-5374}, abstract = {BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We identified 76 miRNAs that were differentially expressed in DCIS and IDC.

METHODS: Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in early-stage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.

RESULTS: Higher expression of miR-301a-3p is associated with poor overall survival in The Can-cer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.

CONCLUSION: We also analyzed competing endogenous networks associated with differentially expressed miRNAs and identified LRRC75A-AS1 and MAGI2-AS3 as lncRNAs that potentially play an important role in early-stage breast cancers.}, } @article {pmid37872454, year = {2023}, author = {Lohani, KR and Hoskin, TL and Day, CN and Yasir, S and Boughey, JC and Degnim, AC}, title = {Lobular-Like Features and Outcomes of Mixed Invasive Ductolobular Breast Cancer (MIDLC): Insights from 54,403 Stage I-III MIDLC Patients.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {37872454}, issn = {1534-4681}, abstract = {BACKGROUND: Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized.

METHOD: The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis.

RESULTS: We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC).

CONCLUSIONS: MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery.}, } @article {pmid37871884, year = {2023}, author = {Grendarova, P and Roumeliotis, M and Quirk, S and Phan, T and Liu, HW and Craighead, P and Lesiuk, M and Pinilla, J and Long, K and Olivotto, IA}, title = {Accelerated Partial Breast Irradiation (APBI) Using Five Daily Fractions: A Prospective, Phase II, Multi-Center Trial of Cosmetic Outcomes and Toxicity: ACCEL Final Results.}, journal = {International journal of radiation oncology, biology, physics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijrobp.2023.10.016}, pmid = {37871884}, issn = {1879-355X}, abstract = {PURPOSE: To investigate cosmetic degradation and toxicity for an APBI prescription delivered in five fractions over one week compared to WBI.

METHODS: The trial is a multicentre, single-arm, phase II, prospective cohort study. Eligible women 50 years of age or older with ER-positive, HER2-negative, invasive ductal carcinoma or ductal carcinoma in situ after breast conserving surgery received 27 Gy in five daily fractions of APBI. The primary endpoint was non-inferiority of two-year cosmesis using the RAPID trial's WBI arm as the control arm. A global, consensus cosmetic score using the EORTC rating scale of excellent, good, fair, or poor for each patient at baseline and two-years was generated by a panel of five radiation oncologists using photographs of treated and untreated breasts.

RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the two-year follow-up, 76 patients were lost or withdrew, and three had died, resulting in 219 patients available for complete, two-year photographic cosmetic evaluation. The median (interquartile range) follow-up for all participants was 4·7 years (3·8 - 5·5 years). No patient had a fair or poor cosmetic score at the two-year evaluation. Cosmesis was better or unchanged for 97% of patients, worse for 3% (excellent to good), and no cosmetic failures. The confidence intervals are 0·88 (0·86-0·90) and 1·00 (0·99-1·00) for the RAPID and ACCEL trials, respectively.

CONCLUSION: Cosmetic degradation of five daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.}, } @article {pmid37870280, year = {2023}, author = {Aydos, U and Ateş, SG and Kurukahvecioğlu, O and Akdemir, ÜÖ and Uyar Göçün, P and Atay, LÖ}, title = {Relationship Between Metabolic Activity, Cellularity, Histopathological Features of Primary Tumors and Distant Metastatic Potential in Breast Cancer.}, journal = {Molecular imaging and radionuclide therapy}, volume = {32}, number = {3}, pages = {195-205}, doi = {10.4274/mirt.galenos.2022.60024}, pmid = {37870280}, issn = {2146-1414}, abstract = {OBJECTIVES: The aim of this study was to evaluate the relationship between the types of distant metastatic spread, histopathological features, and imaging features of primary tumor on positron emission tomography/magnetic resonance imaging (PET/MRI) for primary staging in newly diagnosed breast invasive ductal carcinoma (IDC) patients.

METHODS: Data from 289 female patients were retrospectively evaluated. Maximum standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and minimum apparent diffusion coefficient (ADCmin) values of primary tumors were obtained from PET/MRI. The patients were grouped as non-metastatic, oligometastatic (1-5 metastatic lesions) and multimetastatic (>5 metastatic lesions) disease according to the number of distant metastases, and divided into two groups as isolated bone metastasis (IBM) and mixed/soft tissue metastasis (M-SM) groups according to the sites of metastatic spread.

RESULTS: Metabolic parameters had higher values and ADCmin had lower values in the multimetastatic and oligometastatic groups than in the non-metastatic group. MTV was the only parameter that showed significant difference between the multimetastatic and oligometastatic groups. MTV and TLG were significantly higher in the M-SM group than in the IBM group. [18]F-fluorodeoxyglucose PET parameters had significantly higher values in grade 3, hormone receptor negative, human epidermal growth factor receptor 2 positive, triple negative, and highly proliferative (Ki-67 ≥14%) tumors. The prediction models that included imaging parameters to predict the presence of distant metastasis had higher discriminatory powers than the prediction models that included only histopathological parameters.

CONCLUSION: Primary tumors with higher metabolic-glycolytic activity and higher cellularity were more aggressive and had higher metastatic potential in breast IDC. Compared with histopathological parameters alone, the combination of imaging parameters and histopathological features of primary tumors may help to better understand tumor biology and behavior.}, } @article {pmid37869933, year = {2023}, author = {Bódis, K and Breuer, S and Crepzia-Pevzner, A and Zaharia, OP and Schön, M and Saatmann, N and Altenhofen, D and Springer, C and Szendroedi, J and Wagner, R and Al-Hasani, H and Roden, M and Pesta, D and Chadt, A and , }, title = {Impact of physical fitness and exercise training on subcutaneous adipose tissue beiging markers in humans with and without diabetes and a high-fat diet-fed mouse model.}, journal = {Diabetes, obesity & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.15322}, pmid = {37869933}, issn = {1463-1326}, support = {CH1659//Deutschen Diabetes Stiftung AllgemeineProjektförderung/ ; //EFSD/Novo Nordisk Programme for Diabetes Research/ ; //European Funds for Regional Development/ ; //German Center for Diabetes Research/ ; //German Federal Ministry of Education and Research/ ; //German Federal Ministry of Health/ ; 236177352//German Research Foundation/ ; //Ministry of Culture and Science of the state North Rhine-Westphalia/ ; //Schmutzler Stiftung/ ; }, abstract = {AIMS: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice.

MATERIALS AND METHODS: Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively.

RESULTS: Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity.

CONCLUSIONS: Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity.}, } @article {pmid37869296, year = {2023}, author = {Chen, W and Liu, F and Wang, R and Qi, M and Zhang, J and Liu, X and Song, S}, title = {End-to-end deep learning radiomics: development and validation of a novel attention-based aggregate convolutional neural network to distinguish breast diffuse large B-cell lymphoma from breast invasive ductal carcinoma.}, journal = {Quantitative imaging in medicine and surgery}, volume = {13}, number = {10}, pages = {6598-6614}, pmid = {37869296}, issn = {2223-4292}, abstract = {BACKGROUND: Apart from invasive pathological examination, there is no effective method to differentiate breast diffuse large B-cell lymphoma (DLBCL) from breast invasive ductal carcinoma (IDC). In this study, we aimed to develop and validate an effective deep learning radiomics model to discriminate between DLBCL and IDC.

METHODS: A total of 324 breast nodules from 236 patients with baseline [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) were retrospectively analyzed. After grouping breast DLBCL and breast IDC patients, external and internal datasets were divided according to the data collected by different centers. Preprocessing was then used to process the original PET/CT images and an attention-based aggregate convolutional neural network (AACNN) model was designed. The AACNN model was trained using patches of CT or PET tumor images and optimized with an improved loss function. The final ensemble predictive model was built using distance weight voting. Finally, the model performance was evaluated and statistically verified.

RESULTS: A total of 249 breast nodules from Fudan University Shanghai Cancer Center (FUSCC) and 75 breast nodules from Shanghai Proton and Heavy Ion Center (SPHIC) were selected as internal and external datasets, respectively. On the internal testing, our method yielded an area under the curve (AUC), accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and harmonic mean of precision and sensitivity (F1) of 0.886, 83.0%, 80.9%, 85.0%, 84.8%, 81.2%, and 0.828, respectively. Meanwhile on the external testing, the results were 0.788, 71.6%, 61.4%, 84.7%, 84.0%, 62.6%, and 0.709, respectively.

CONCLUSIONS: Our study outlines a deep learning radiomics method which can automatically, noninvasively, and accurately differentiate breast DLBCL from breast IDC, which will be more in line with the needs and strategies of precision medicine, individualized diagnosis, and treatment.}, } @article {pmid37862374, year = {2023}, author = {Tsilingiris, D and Schimpfle, L and Rauchhaupt, EV and Sulaj, A and Seebauer, L and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z}, title = {Sensory phenotypes provide insight into the natural course of diabetic polyneuropathy.}, journal = {Diabetes}, volume = {}, number = {}, pages = {}, doi = {10.2337/db23-0271}, pmid = {37862374}, issn = {1939-327X}, abstract = {We aimed to investigate the characteristics and longitudinal course of sensory phenotypes identified through Quantitative Sensory Testing in the frame of diabetic polyneuropathy (DSPN). 316 individuals with diabetes mellitus (DM) were examined (78.8% T2DM), of which 250 were follow-up visits 1, 2 and/or 4 (2.88±1.27) years. Allocation into four sensory phenotypes (healthy, thermal hyperalgesia-TH, mechanical hyperalgesia-MH, and sensory loss-SL) at every timepoint was based on QST profiles of the right foot. Cross-sectional analyses demonstrated a gradual worsening of clinical and electrophysiological sensory findings, and increased DSPN prevalence across the groups culminating in SL. Motor nerve impairment was observed solely in SL. Longitudinal analysis revealed a distinct pattern of the phenotype's developmental course (healthy to TH, to MH, to SL). Baseline MH exhibited the highest risk of transition to SL. Regression to healthy was uncommon and mostly observed in TH. Among those without DSPN initially, presence or future occurrence of SL was associated with a three- to fivefold higher likelihood of DSPN development. Our comprehensive longitudinal study of phenotyped patients with DM elucidates the natural course of DSPN. QST-based sensory examination together with other tools for phenotyping may perhaps be useful to determine the natural course of diabetic neuropathy, to identify patients at high risk for DSPN and guide preventive and therapeutic interventions.}, } @article {pmid37856936, year = {2023}, author = {Mansour, O and Kazem, A and El Wakil, A}, title = {Assessment of breast cytoarchitecture and its associated axillary lymph node status under normal and pathological conditions in Egyptian women.}, journal = {Tissue & cell}, volume = {85}, number = {}, pages = {102244}, doi = {10.1016/j.tice.2023.102244}, pmid = {37856936}, issn = {1532-3072}, abstract = {OBJECTIVE: Herein, we compare the features of neoplastic cancer cells in invasive ductal carcinoma (IDC) grade II and III patients to their corresponding normal cells both in breast and axillary lymph node (ALN) tissues.

METHODS: A retrospective cohort of 70 female breast cancer patients enrolled between 2018 and 2020 at Medical Research Institute, Alexandria University, Egypt, was analyzed for clinicopathological features presentation. Fresh tiny pieces of breast tissue and its associated ALN tissues were then processed to investigate the morphological appearance by scanning electron microscopy. Moreover, the histological architecture of tissue sections stained with hematoxylin and eosin was studied by light microscope, while the characterization of the ultrastructure features of breast and ALN tissues was analyzed by transmission electron microscopy.

RESULTS: Clinicopathological presentation of patients revealed that the Egyptian female breast cancer population adhered to the global trends of breast cancer disease with elevated incidence rate among postmenopausal women (61.3%), high frequency of IDC (95.7%), and increased ALN metastasis (65.7%). The percentage of estrogen receptor alpha (ERα) and human epidermal growth factor receptor 2 (HER2) expression, as key indicators for carcinogenesis and disease progression was 87.1% and 55.8%, respectively. The present study points to the observed discrepancies among the investigated variables in the diagnostic separation between IDC grade II and grade III. Ductal epithelial cells organization, nuclei size and irregularity, chromatin amount and uniformity, mitochondrial abundance and dysfunction were differentially manifested in IDC grades. Moreover, aberrations in the cellular organelles like lysosomes, endoplasmic reticulum, and lipid droplets vary according to the grade of IDC and the aggressiveness of the invasive breast cancer.

CONCLUSIONS: To sum up, this study emphasizes the importance of accurate specimen evaluation for treatment choice and decision.}, } @article {pmid37855288, year = {2023}, author = {Mohammed, BT and Uzodi, N and Gotimukul, A and Kokebie, R}, title = {Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.}, journal = {Current rheumatology reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115733971246438230924163114}, pmid = {37855288}, issn = {1875-6360}, abstract = {BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.

CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.

CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.}, } @article {pmid37848693, year = {2023}, author = {Özdemir, A and Güven, M and Binici, S and Uygur, S and Toktaş, O}, title = {Impact of 18F-FDG PET/CT in the management decisions of breast cancer board on early-stage breast cancer.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {37848693}, issn = {1699-3055}, abstract = {PURPOSE: Breast cancer is the most common malignancy accounting for 11.7% of all cancer cases, with a rising incidence rate. Various diagnostic methods, including 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), play a crucial role in breast cancer diagnosis and staging. However, the unnecessary use of advanced imaging techniques such as PET/CT in early-stage breast cancer can have negative effects on both economics and patients. We aimed to investigate the impact of PET/CT on the management decisions of early-stage breast cancer patients by the breast cancer tumor board.

METHODS: A retrospective analysis was performed on a cohort of 81 patients with early-stage breast cancer who were evaluated by breast cancer tumor board from January 2015 to December 2020. Demographic, clinical, and radiographic data, along with surgical procedures and treatment options, were documented and analyzed.

RESULTS: The results showed that 18F-FDG PET/CT had a moderate impact on treatment decisions of breast cancer tumor board, as only treatment decisions were changed in 14,86% of the patients. The surgical procedure decision of breast cancer tumor board changed in 12.35% of patients, while 87.65% of patients had consistent decisions before and after PET/CT. Pathological assessments revealed invasive ductal carcinoma as the most prevalent tumor type, and molecular subtypes were predominantly luminal B. PET/CT use had limited impact on surgical procedures and did not significantly alter treatment decisions of breast cancer tumor board in this early-stage breast cancer cohort.

CONCLUSIONS: In conclusion, this study highlights the importance of adherence to the guidelines and appropriate use of PET/CT in early-stage breast cancer management. PET/CT should be reserved for cases where it is clinically warranted, considering the potential economic burden and minimal impact on treatment decisions of breast cancer tumor board in this patient population.}, } @article {pmid37847513, year = {2023}, author = {Zhao, J and Zhu, S and Nie, L and Zhang, M and Zheng, L and Xu, N and Cai, D and Sun, X and Chen, J and Dai, J and Ni, Y and Wang, Z and Zhang, X and Liang, J and Chen, Y and Hu, X and Pan, X and Yin, X and Liu, H and Zhao, F and Zhang, B and Chen, H and Miao, J and Qin, C and Zhao, X and Yao, J and Liu, Z and Liao, B and Wei, Q and Li, X and Liu, J and Gao, AC and Huang, H and Shen, PF and Chen, N and Zeng, H and Sun, G}, title = {Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.}, journal = {Cancer research}, volume = {}, number = {}, pages = {}, doi = {10.1158/0008-5472.CAN-23-1176}, pmid = {37847513}, issn = {1538-7445}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally co-exists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared to concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathological heterogeneity between IDC-P and PAC. Compared to co-existing PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 metastatic prostate cancer patients revealed that IDC-P carriers with lower risk ISUP grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.}, } @article {pmid37835856, year = {2023}, author = {Khalid, A and Mehmood, A and Alabrah, A and Alkhamees, BF and Amin, F and AlSalman, H and Choi, GS}, title = {Breast Cancer Detection and Prevention Using Machine Learning.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, doi = {10.3390/diagnostics13193113}, pmid = {37835856}, issn = {2075-4418}, abstract = {Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.}, } @article {pmid37835373, year = {2023}, author = {Porter, BA and Frerich, C and Lainé, M and Clark, AB and Durdana, I and Lee, J and Taya, M and Sahoo, S and Greene, GL and Bennett, L and Conzen, SD}, title = {Glucocorticoid Receptor Activation in Lobular Breast Cancer Is Associated with Reduced Cell Proliferation and Promotion of Metastases.}, journal = {Cancers}, volume = {15}, number = {19}, pages = {}, doi = {10.3390/cancers15194679}, pmid = {37835373}, issn = {2072-6694}, support = {P30 CA142543/CA/NCI NIH HHS/United States ; }, abstract = {Estrogen receptor-positive (ER+) invasive lobular breast cancer (ILC) comprises about ~15% of breast cancer. ILC's unique genotypic (loss of wild type E-cadherin expression) and phenotypic (small individual round cancer cells that grow in discontinuous nests) are thought to contribute to a distinctive pattern of metastases to serosal membranes. Unlike invasive ductal carcinoma (IDC), ILC metastases often intercalate into the mesothelial layer of the peritoneum and other serosal surfaces. While ER activity is a known driver of ILC proliferation, very little is known about how additional nuclear receptors contribute to ILC's distinctive biology. In ER+ IDC, we showed previously that glucocorticoid receptor (GR) activity inhibits pro-proliferative gene expression and cell proliferation. Here we examined ER+ ILC models and found that GR activation similarly reduces S-phase entry gene expression and ILC proliferation. While slowing tumor growth rate, our data also suggest that GR activation results in an enhanced metastatic phenotype through increasing integrin-encoding gene expression, extracellular matrix protein adhesion, and mesothelial cell clearance. Moreover, in an intraductal mouse mammary gland model of ILC, we found that GR expression is associated with increased bone metastases despite slowed primary mammary tumor growth. Taken together, our findings suggest GR-mediated gene expression may contribute to the unusual characteristics of ILC biology.}, } @article {pmid37833450, year = {2023}, author = {Rothschild, HT and Clelland, EN and Abel, MK and Chien, AJ and Shui, AM and Esserman, L and Khan, SA and Mukhtar, RA}, title = {The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {37833450}, issn = {1573-7217}, support = {TL1 TR 001871/TR/NCATS NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.

METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses.

RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden.

CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.}, } @article {pmid37833434, year = {2023}, author = {Yu, Q and Wan, D and Fu, R and Li, F and Zhang, Y}, title = {Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {17346}, pmid = {37833434}, issn = {2045-2322}, support = {no. 2019YLSF03//the Key Science and Technology Project of Zigong, China/ ; }, abstract = {The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis-trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1-2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II-III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.}, } @article {pmid37832430, year = {2023}, author = {Schacherer, DP and Herrmann, MD and Clunie, DA and Höfener, H and Clifford, W and Longabaugh, WJR and Pieper, S and Kikinis, R and Fedorov, A and Homeyer, A}, title = {The NCI Imaging Data Commons as a platform for reproducible research in computational pathology.}, journal = {Computer methods and programs in biomedicine}, volume = {242}, number = {}, pages = {107839}, doi = {10.1016/j.cmpb.2023.107839}, pmid = {37832430}, issn = {1872-7565}, abstract = {BACKGROUND AND OBJECTIVES: Reproducibility is a major challenge in developing machine learning (ML)-based solutions in computational pathology (CompPath). The NCI Imaging Data Commons (IDC) provides >120 cancer image collections according to the FAIR principles and is designed to be used with cloud ML services. Here, we explore its potential to facilitate reproducibility in CompPath research.

METHODS: Using the IDC, we implemented two experiments in which a representative ML-based method for classifying lung tumor tissue was trained and/or evaluated on different datasets. To assess reproducibility, the experiments were run multiple times with separate but identically configured instances of common ML services.

RESULTS: The results of different runs of the same experiment were reproducible to a large extent. However, we observed occasional, small variations in AUC values, indicating a practical limit to reproducibility.

CONCLUSIONS: We conclude that the IDC facilitates approaching the reproducibility limit of CompPath research (i) by enabling researchers to reuse exactly the same datasets and (ii) by integrating with cloud ML services so that experiments can be run in identically configured computing environments.}, } @article {pmid37830404, year = {2023}, author = {Melli, G and Caccico, L and Micheli, E and Bulli, F and Doron, G}, title = {Pathological narcissism and relationship obsessive-compulsive disorder (ROCD) symptoms: Exploring the role of vulnerable narcissism.}, journal = {Journal of clinical psychology}, volume = {}, number = {}, pages = {}, doi = {10.1002/jclp.23601}, pmid = {37830404}, issn = {1097-4679}, abstract = {OBJECTIVE: Relationship obsessive-compulsive disorder (ROCD) symptoms, which include obsessive preoccupation, doubts, and compulsive behaviors focusing on the suitability of the relationship and/or partner, have been receiving increasing clinical, theoretical, and empirical attention. This clinical variant of OCD is associated with significant functional, personal, and dyadic consequences. ROCD symptoms have also been linked to several cognitive vulnerability factors, such as maladaptive relationship catastrophization. However, little is known about the connection between ROCD symptoms and specific personality traits. In this study, we examine whether vulnerable narcissistic personality traits may constitute a general vulnerability factor for ROCD symptoms. Specifically, we assess whether partner value self-contingencies moderate the association between vulnerable narcissistic traits and obsessive preoccupation with a romantic partner's perceived flaws.

METHOD: A total of 310 individuals self-reporting ROCD symptoms completed questionnaires assessing narcissistic personality traits, ROCD symptoms and cognitions, and partner value self-contingencies.

RESULTS: Vulnerable narcissistic traits were uniquely associated with ROCD symptoms over and above ROCD-related cognitions. Self-worth contingent on the partner's perceived value partially mediated the effect of vulnerable narcissistic traits on ROCD symptoms.

CONCLUSION: Results supported the role of vulnerable narcissistic traits and domain-relevant self-vulnerabilities on obsessive preoccupation with romantic partners' perceived flaws. Further research is needed to explore the susceptibility of vulnerable individuals to the development and maintenance of ROCD symptoms.}, } @article {pmid37828835, year = {2023}, author = {Yang, SY and Zhang, J and Yang, ZQ and Duan, JJ and Zhang, Y and Li, MK and Wang, L and Ye, CM and Nie, JY}, title = {Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.}, journal = {Science progress}, volume = {106}, number = {4}, pages = {368504231201043}, doi = {10.1177/00368504231201043}, pmid = {37828835}, issn = {2047-7163}, abstract = {The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.}, } @article {pmid37824772, year = {2023}, author = {Dieu Vuong, L and Ngoc Nguyen, Q}, title = {ABERRANT METHYLATION OF CANCER-RELATED GENES IN VIETNAMESE BREAST CANCER PATIENTS: ASSOCIATIONS WITH CLINICOPATHOLOGICAL FEATURES.}, journal = {Experimental oncology}, volume = {45}, number = {2}, pages = {195-202}, doi = {10.15407/exp-oncology.2023.02.195}, pmid = {37824772}, issn = {2312-8852}, abstract = {BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).

AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.

MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.

RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.

CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.}, } @article {pmid37821332, year = {2023}, author = {Ghuman, N and Ambinder, EB and Oluyemi, ET and Sutton, E and Myers, KS}, title = {Clinical and Imaging Features of MRI Screen-Detected Breast Cancer.}, journal = {Clinical breast cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clbc.2023.09.012}, pmid = {37821332}, issn = {1938-0666}, abstract = {BACKGROUND: Supplemental screening with breast MRI is recommended annually for patients who have greater than 20% lifetime risk for breast cancer. While there is robust data regarding features of mammographic screen-detected breast cancers, there is limited data regarding MRI-screen-detected cancers.

PATIENTS AND METHODS: Screening breast MRIs performed between August 1, 2016 and July 30, 2022 identified 50 screen-detected breast cancers in 47 patients. Clinical and imaging features of all eligible cancers were recorded.

RESULTS: During the study period, 50 MRI-screen detected cancers were identified in 47 patients. The majority of MRI-screen detected cancers (32/50, 64%) were invasive. Pathology revealed ductal carcinoma in situ (DCIS) in 36% (18/50), invasive ductal carcinoma (IDC) in 52% (26/50), invasive lobular carcinoma in 10% (5/50), and angiosarcoma in 2% (1/50). The majority of patients (43/47, 91%) were stage 0 or 1 at diagnosis and there were no breast cancer-related deaths during the follow-up periods. Cancers presented as masses in 50% (25/50), nonmass enhancement in 48% (25/50), and a focus in 2% (1/50). DCIS was more likely to present as nonmass enhancement (94.4%, 17/18), whereas invasive cancers were more likely to present as masses (75%, 24/32) (P < .001). All cancers that were stage 2 at diagnosis were detected either on a baseline exam or more than 4 years since the prior MRI exam.

CONCLUSION: MRI screen-detected breast cancers were most often invasive cancers. Cancers detected by MRI screening had an excellent prognosis in our study population. Invasive cancers most commonly presented as a mass.}, } @article {pmid37812297, year = {2023}, author = {Tsai, HY and Kao, YW and Wang, JC and Tsai, TY and Chung, WS and Hsu, JS and Hou, MF and Weng, SF}, title = {Multitask deep learning on mammography to predict extensive intraductal component in invasive breast cancer.}, journal = {European radiology}, volume = {}, number = {}, pages = {}, pmid = {37812297}, issn = {1432-1084}, support = {SI-10911//Kaohsiung Medical University Chung-Ho Memorial Hospital/ ; SI-11008//Kaohsiung Medical University Chung-Ho Memorial Hospital/ ; }, abstract = {OBJECTIVES: To develop a multitask deep learning (DL) algorithm to automatically classify mammography imaging findings and predict the existence of extensive intraductal component (EIC) in invasive breast cancer.

METHODS: Mammograms with invasive breast cancers from 2010 to 2019 were downloaded for two radiologists performing image segmentation and imaging findings annotation. Images were randomly split into training, validation, and test datasets. A multitask approach was performed on the EfficientNet-B0 neural network mainly to predict EIC and classify imaging findings. Three more models were trained for comparison, including a single-task model (predicting EIC), a two-task model (predicting EIC and cell receptor status), and a three-task model (combining the abovementioned tasks). Additionally, these models were trained in a subgroup of invasive ductal carcinoma. The DeLong test was used to examine the difference in model performance.

RESULTS: This study enrolled 1459 breast cancers on 3076 images. The EIC-positive rate was 29.0%. The three-task model was the best DL model with an area under the curve (AUC) of EIC prediction of 0.758 and 0.775 at the image and breast (patient) levels, respectively. Mass was the most accurately classified imaging finding (AUC = 0.915), followed by calcifications and mass with calcifications (AUC = 0.878 and 0.824, respectively). Cell receptor status prediction was less accurate (AUC = 0.625-0.653). The multitask approach improves the model training compared to the single-task model, but without significant effects.

CONCLUSIONS: A mammography-based multitask DL model can perform simultaneous imaging finding classification and EIC prediction.

CLINICAL RELEVANCE STATEMENT: The study results demonstrated the potential of deep learning to extract more information from mammography for clinical decision-making.

KEY POINTS: • Extensive intraductal component (EIC) is an independent risk factor of local tumor recurrence after breast-conserving surgery. • A mammography-based deep learning model was trained to predict extensive intraductal component close to radiologists' reading. • The developed multitask deep learning model could perform simultaneous imaging finding classification and extensive intraductal component prediction.}, } @article {pmid37811173, year = {2023}, author = {Parashar, S and Arora, J and Mittal, A}, title = {Bright Is Not Always Better: A Pictorial Review of Hyperechoic Malignant Breast Masses.}, journal = {The Indian journal of radiology & imaging}, volume = {33}, number = {4}, pages = {532-540}, pmid = {37811173}, issn = {0971-3026}, abstract = {Hyperechogenic breast lesions are a relatively rare finding at breast ultrasonography and are traditionally thought to be benign. However, hyperechogenicity on the ultrasound alone does not provide enough evidence to rule out malignancy completely. We herein reported a short series of nine cases of echogenic malignant breast lesions, which include invasive ductal carcinoma, ductal carcinoma in situ, invasive lobular carcinoma, angiosarcoma, lymphoma, and metastasis to the breast. Echogenic breast lesions should be carefully evaluated and properly categorized based on any other suspicious sonographic characteristics and must be correlated with mammographic findings and clinical history to lower the threshold for biopsy and avoid delay in diagnosis. Hyperechogenicity should not be considered as a characteristically benign feature and should not supersede the less specifically benign features of the same lesion on the other examination.}, } @article {pmid37811111, year = {2023}, author = {Mansour, M and Zahra, O and Nabulsi, D and Alhamwi, A and Chahin, M and Alani, WR and Yousef, D and Kanbour, I and Kurdi, B and Mohammad Deeb, A}, title = {Ectopic primary ductal breast carcinoma of the vulva: a case report and literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5138-5144}, pmid = {37811111}, issn = {2049-0801}, abstract = {BACKGROUND: Ectopic breast tissue (EBT) is normally found along the rudimentary mammary line, which is located from the axilla to the inguinal region and disappears during embryogenesis. Up to 6% of females around the world suffer from EBT. EBT cancer is rare, with only a few reports in the literature. The diagnosis, and treatment of these rare cases can be very difficult and complex.

CASE PRESENTATION: The authors report an interesting case of a 74-year-old female patient with a vulvar lump located on the mons pubis associated with ulceration, pain, and size increase. The histopathological study demonstrated an invasive ductal carcinoma grade 2 arising from EBT in the vulva. Within 4 months of follow-up, the patient's condition was stable.

Throughout this paper, the authors aim to highlight the diagnostic and therapeutic challenges since there are no current guidelines for treatment for such cases. Furthermore, this article describes this rare disease and includes surgical details, difficulties, diagnostic methods, and treatment options.}, } @article {pmid37811031, year = {2023}, author = {Rhoul, C and Kharkhach, A and Aabdi, H and Atmani, A and Mhand, M and Seghrouchni, N and Amal, B and Bouhout, T and Serji, B and El Harroudi, T}, title = {Radiation-induced angiosarcoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {5047-5050}, pmid = {37811031}, issn = {2049-0801}, abstract = {INTRODUCTION: Breast angiosarcoma is a rare, aggressive tumour affecting adult women. It can occur in two forms, primary form and secondary forms or radiation-induced breast angiosarcoma affecting patients with history of breast or chest radiotherapy.

CASE PRESENTATION: The authors report a new case of breast angiosarcoma in 52-year-old women, with history of invasive ductal carcinoma, and reporting a discoloration of her breast skin. The patient did undergo a mastectomy of right breast and adjuvant chemotherapy.

CONCLUSION/DISCUSSION: Surgery with total excision associated or not to adjuvant chemotherapy remains the treatment of choice in breast angiosarcoma.}, } @article {pmid37807773, year = {2023}, author = {Gozalishvilli-Boncheva, A and Gonzalez-Espinoza, IR and Castro-Ponce, A and Bravo-Gutiérrez, OA and Juárez-Salazar, G and Montes-de-Oca-Moreda, RI and Aguirre-Flores, E and Coyotl-Huexotl, M and Orozco-Luis, J and Chiquillo-Domínguez, M and Garibay-Díaz, JC and Aranda-Claussen, JE and Ponce-de-León, EA and Sánchez-Sosa, S and Sabaté-Fernández, M and García-Reyna, JC and Cordero-Vargas, C and González-Blanco, MJ and Aguilar-Priego, JM and Sánchez-Fernández, NJ and Cortés-García, CA and González-Lozada, LE and Miguel-Cruz, E and Ceja-Utrera, FJ and Hernández-Garcia, MS and Piña-Vazquez, M and Aguilar-Jiménez, C}, title = {Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.}, journal = {Breast disease}, volume = {42}, number = {1}, pages = {305-313}, doi = {10.3233/BD-230025}, pmid = {37807773}, issn = {1558-1551}, abstract = {Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.}, } @article {pmid37800299, year = {2023}, author = {Takashima, Y and Terasawa, R and Hirata, A and Morita, S and Kimura, K and Iwamoto, M and Hayashi, M}, title = {[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {9}, pages = {1009-1011}, pmid = {37800299}, issn = {0385-0684}, abstract = {The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.}, } @article {pmid37798148, year = {2023}, author = {Aitken, GL and Samuels, S and Gannon, CJ and Llaguna, OH}, title = {Influence of contralateral prophylactic mastectomy on textbook outcome attainment at time of mastectomy.}, journal = {American journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjsurg.2023.09.050}, pmid = {37798148}, issn = {1879-1883}, abstract = {INTRODUCTION: The objective of this study was to determine the incidence of textbook oncologic outcome (TOO) and its impact on overall survival (OS) among patients with invasive ductal carcinoma (IDC) following modified radical mastectomy (MRM) versus MRM with contralateral prophylactic mastectomy (MRM + CPM).

METHODS: The 2004-2017 National Cancer Database was queried for patients with IDC who underwent MRM and MRM ​+ ​CPM. TOO was defined as: resection with negative margins, adequate lymphadenectomy, length of stay ≤50th percentile, and no 30-day readmission or mortality.

RESULTS: 87,573 patients were identified, of which 14.3% underwent MRM ​+ ​CPM. Logistic regression models revealed that MRM ​+ ​CPM is independently associated with a reduced likelihood of achieving TOO (AOR ​= ​0.71; P ​< ​0.001). MRM patients who achieved TOO had a higher median OS compared to those who did not (164.6 vs.142.2 months, P ​< ​0.001).

CONCLUSIONS: MRM ​+ ​CPM is associated with a lower incidence of TOO attainment compared to MRM.}, } @article {pmid37792368, year = {2023}, author = {Martelli, G and Barretta, F and Vernieri, C and Folli, S and Pruneri, G and Segattini, S and Trapani, A and Carolla, C and Spatti, G and Miceli, R and Ferraris, C}, title = {Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.}, journal = {JAMA surgery}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamasurg.2023.4770}, pmid = {37792368}, issn = {2168-6262}, abstract = {IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.

OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.

This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.

EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.

MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.

RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.

CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.}, } @article {pmid37790038, year = {2023}, author = {Bahadure, SD and Noman, O and Jaiswal, N and Bandre, G and Akulwar, A}, title = {Incidental Finding of Invasive Ductal Carcinoma on Mastectomy in the Case of Lymphocytic Mastitis: A Case Report.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44545}, pmid = {37790038}, issn = {2168-8184}, abstract = {A rare inflammatory breast disorder called lymphocytic mastitis is characterized by lymphocyte infiltrates in the mammary parenchyma. Due to their rarity, incidental observations of invasive ductal carcinoma in lymphocytic mastitis present diagnostic and management challenges. We present a case of a 52-year-old female with a history of painfully swollen breasts for three months who underwent a core needle biopsy, consistent with lymphocytic mastitis on histopathology. Due to persistent and worsening symptoms, a mastectomy was performed. During the examination, an incidental finding of infiltrating ductal carcinoma was identified in the mastectomy specimen. This unexpected discovery led to further investigations and altered the patient's treatment plan. The detection of invasive ductal carcinoma in the presence of lymphocytic mastitis highlights the importance of continuous surveillance and thorough examination. In the circumstances of lymphocytic mastitis, it is vital to take the likelihood of concurrent malignancy into account, especially when symptoms persist or reappear after appropriate management. This case report seeks to raise awareness among physicians of this exceptional association and drive further research that will explain its pathophysiology while enhancing management strategies.}, } @article {pmid37787287, year = {2023}, author = {Chaudhary, D and Balhara, K and Mandal, S and Mallya, V and Tomar, R and Khurana, N and Bains, L}, title = {Metaplastic breast carcinoma: Analysis of clinical and pathologic features, a five-year study.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {5}, pages = {1226-1230}, doi = {10.4103/jcrt.jcrt_1229_21}, pmid = {37787287}, issn = {1998-4138}, abstract = {BACKGROUND: Metaplastic carcinoma breast (MCB) is a rare tumor comprising of both glandular and non-glandular patterns with epithelial and or mesenchymal components. Due to their varied clinicomorphological features, diagnosis has been challenging.

AIM: To study the clinicopathological and histomorphology of cases of metaplastic carcinoma breast diagnosed in a tertiary care hospital along with literature review.

MATERIALS AND METHODS: This is a retrospective study including data of 11 patients who were diagnosed with MCB either on trucut or mastectomy specimens conducted between January 2014 and December 2018.

RESULTS: The study includes 11 patients, out of which 10 were diagnosed on mastectomy while one on trucut specimen. All the patients were women with the mean age of presentation being 43.8 years. The most common presentation was palpable breast lump with mean tumor size of 7.3 cm in greatest dimension. Skin involvement was seen in 36.3% of cases. While eight cases (72.7%) were classified as epithelial, three (27.2%) were classified as mixed. Amongst epithelial variety, in eight cases, squamous component was seen along with infiltrating ductal carcinoma (IDC) while one was pure squamous type. In mixed variety, one case showed spindled areas along with squamous areas and areas of IDC. Other two showed focal sarcomatous and cartilaginous areas in one and angiosarcomatous, bone and cartilage formation admixed with areas of IDC in other case.

CONCLUSION: MCB are rare breast tumors with aggressive course and are characterized by their large size and rapid growth rate. Recently, there has been an upsurge in the cases of MCB due to increase in recognition of this entity. It has to be distinguished from other tumors by the pathologists so as to guide proper treatment.}, } @article {pmid37783506, year = {2023}, author = {Bola, Ł and Vetter, P and Wenger, M and Amedi, A}, title = {Decoding reach direction in early "visual" cortex of congenitally blind individuals.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1523/JNEUROSCI.0376-23.2023}, pmid = {37783506}, issn = {1529-2401}, abstract = {Motor actions, such as reaching or grasping, can be decoded from fMRI activity of early visual cortex in sighted humans. This effect can depend on vision or visual imagery, or alternatively, could be driven by mechanisms independent of visual experience. Here, we show that the actions of reaching in different directions can be reliably decoded from fMRI activity of early visual cortex in congenitally blind humans (both sexes). Thus, neither visual experience nor visual imagery is necessary for early visual cortex to represent action-related information. We also demonstrate that, within early visual cortex of blind humans, the accuracy of reach direction decoding is highest in areas typically representing foveal vision and gradually decreases in areas typically representing peripheral vision. We propose that this might indicate the existence of a predictive, hard-wired mechanism of aligning action and visual spaces. This mechanism might send action-related information primarily to the high-resolution foveal visual areas, which are critical for guiding and online correction of motor actions. Finally, we show that, beyond early visual cortex, the decoding of reach direction in blind humans is most accurate in dorsal stream areas known to be critical for visuo-spatial and visuo-motor integration in the sighted. Thus, these areas can develop space and action representations even in the lifelong absence of vision. Overall, our findings in congenitally blind humans match previous research on the action system in the sighted, and suggest that the development of action representations in the human brain might be largely independent of visual experience.Significance StatementEarly visual cortex (EVC) was traditionally thought to process only visual signals from the retina. Recent studies proved this account incomplete, and showed EVC involvement in many activities not directly related to incoming visual information, such as memory, sound, or action processing. Is EVC involved in these activities because of visual imagery? Here, we show robust reach direction representation in EVC of humans born blind. This demonstrates that EVC can represent actions independently of vision and visual imagery. Beyond EVC, we found that reach direction representation in blind humans is strongest in dorsal brain areas, critical for action processing in the sighted. This suggests that the development of action representations in the human brain is largely independent of visual experience.}, } @article {pmid37781368, year = {2023}, author = {Wang, W and Truong, K and Ye, C and Sharma, S and He, H and Liu, L and Wen, M and Misra, A and Zhou, P and Kimata, JT}, title = {Engineered CD4 T cells expressing a membrane anchored viral inhibitor restrict HIV-1 through cis and trans mechanisms.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1167965}, pmid = {37781368}, issn = {1664-3224}, support = {S10 OD028480/OD/NIH HHS/United States ; R33 AI116167/AI/NIAID NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R21 AI116167/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 AI106574/AI/NIAID NIH HHS/United States ; P30 AI161943/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *HIV-1 ; CD4-Positive T-Lymphocytes ; *HIV Infections ; HIV Antibodies ; Cell Line ; *HIV Seropositivity ; *Single-Chain Antibodies/pharmacology ; }, abstract = {HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4[+] cell lines by transduction with X5 derived anti-HIV-1 Env antibody linked to a GPI attachment signal directs GPI-anchored scFvs into lipid rafts of the plasma membrane. In this study, we further characterize the effect of GPI-scFv X5 on cell-cell HIV-1 transmission from DCs to target cells. We report that expression of GPI-scFv X5 in transduced CD4[+] cell lines and human primary CD4[+] T cells potently restricts viral replication in iDC- or mDC-captured HIV-1 in trans. Using live-cell imaging, we observed that when GPI-GFP or GPI-scFv X5 transduced T cells are co-cultured with iDCs, GPI-anchored proteins enrich in contact zones and subsequently migrate from T cells into DCs, suggesting that transferred GPI-scFv X5 interferes with HIV-1 infection of iDCs. We conclude that GPI-scFv X5 on the surface of transduced CD4[+] T cells not only potently blocks cell-mediated infection by DCs, but it transfers from transduced cells to the surface of iDCs and neutralizes HIV-1 replication in iDCs. Our findings have important implications for HIV-1 antibody-based immunotherapies as they demonstrate a viral inhibitory effect that extends beyond the transduced CD4+ T cells to iDCs which can enhance HIV-1 replication.}, } @article {pmid37771380, year = {2023}, author = {Asare, B and White, MJ and Rossi, J}, title = {Metaplastic carcinoma with osteosarcomatous differentiation in the breast: Case report.}, journal = {Radiology case reports}, volume = {18}, number = {12}, pages = {4272-4280}, pmid = {37771380}, issn = {1930-0433}, abstract = {Metaplastic breast carcinoma is rare and may present as a highly aggressive subtype of breast cancer. In this case report of metastatic metaplastic breast carcinoma with osteosarcomatous differentiation in a female patient previously treated for invasive ductal carcinoma, we describe the new presentation of a palpable mass with associated calcifications on imaging near the site of prior partial mastectomy. This article will detail the clinical presentation, imaging findings, histopathology, and clinical course following treatment of our case. Knowledge of the clinical and imaging presentation of this rare subtype, which can present with benign features on mammography and ultrasound, can facilitate timely diagnosis as treatment paradigms evolve.}, } @article {pmid37769530, year = {2023}, author = {Siregar, KB and Al Anas, M}, title = {Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100764}, doi = {10.1016/j.ctarc.2023.100764}, pmid = {37769530}, issn = {2468-2942}, abstract = {INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.

METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.

RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).

CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.}, } @article {pmid37761331, year = {2023}, author = {Al-Refai, R and Bendari, A and Morrar, D and Sham, S and Kataw, L and Garajayev, A and Hajiyeva, S}, title = {Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761331}, issn = {2075-4418}, abstract = {Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.}, } @article {pmid37749321, year = {2023}, author = {Taylor, J and Uhl, L and Moll, I and Hasan, SS and Wiedmann, L and Morgenstern, J and Giaimo, BD and Friedrich, T and Alsina-Sanchis, E and De Angelis Rigotti, F and Mülfarth, R and Kaltenbach, S and Schenk, D and Nickel, F and Fleming, T and Sprinzak, D and Mogler, C and Korff, T and Billeter, AT and Müller-Stich, BP and Berriel Diaz, M and Borggrefe, T and Herzig, S and Rohm, M and Rodriguez-Vita, J and Fischer, A}, title = {Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.}, journal = {Nature cancer}, volume = {}, number = {}, pages = {}, pmid = {37749321}, issn = {2662-1347}, support = {394046768 - SFB1366//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1118-A04/S01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BO 1639/9-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.}, } @article {pmid37747019, year = {2023}, author = {Choi, JH and Yu, J and Jung, M and Jekal, J and Kim, KS and Jung, SU}, title = {Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.}, journal = {Medicine}, volume = {102}, number = {38}, pages = {e35267}, pmid = {37747019}, issn = {1536-5964}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics ; Prognosis ; Mastectomy ; High-Throughput Nucleotide Sequencing ; Class I Phosphatidylinositol 3-Kinases/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.}, } @article {pmid37745509, year = {2023}, author = {Stindt, KR and McClean, MN}, title = {Tuning Interdomain Conjugation Toward in situ Population Modification in Yeast.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.12.557379}, pmid = {37745509}, abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes, and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to widespread use of IDC is its limited efficiency. In this work, we utilize interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture, and model how these tunable controls can predictably yield a range of IDC outcomes. Further, we demonstrate that these lessons can be utilized to lastingly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.}, } @article {pmid37743485, year = {2023}, author = {Pourriahi, R and Omranipour, R and Alipour, S and Hajimaghsoudi, L and Mashoori, N and Kenary, AY and Motamedi, M and Tavakol, M and Mohammadzadeh, M and Hessamiazar, S and Shabani, S and Mahmoodi, F and Goodarzi, MM and Eslami, B}, title = {Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {511}, pmid = {37743485}, issn = {1472-6874}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/epidemiology ; Iran/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Palpation ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.

METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.

RESULTS: A total of 1476 patients with a mean age of 48.03 (± 11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.

CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.}, } @article {pmid37738898, year = {2023}, author = {Peng, L and He, X and Peng, X and Li, Z and Zhang, L}, title = {STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.}, journal = {Computers in biology and medicine}, volume = {166}, number = {}, pages = {107440}, doi = {10.1016/j.compbiomed.2023.107440}, pmid = {37738898}, issn = {1879-0534}, abstract = {BACKGROUND: Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background.

METHODS: We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets.

RESULTS: We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters.

CONCLUSION: We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.}, } @article {pmid37738835, year = {2023}, author = {Coffey, K and Dixon, LB and Sevilimedu, V and Jochelson, MS and Sung, JS}, title = {Short-term follow-up of contrast-enhanced mammography lesions after negative breast MRI in women with elevated breast cancer risk.}, journal = {European journal of radiology}, volume = {168}, number = {}, pages = {111097}, doi = {10.1016/j.ejrad.2023.111097}, pmid = {37738835}, issn = {1872-7727}, abstract = {PURPOSE: To determine the outcome of enhancing lesions detected on contrast-enhanced mammography (CEM) that had no correlate on magnetic resonance imaging (MRI) and underwent short-term follow-up CEM.

METHODS: In this retrospective single-center study, we identified patients with elevated breast cancer risk who had a CEM between 2014 and 2021 showing indeterminate enhancement on recombined images (BI-RADS 0, 3, 4) that had no correlate on subsequent MRI (performed within one month), and therefore underwent short-term follow-up CEM (performed within eight months). Medical records and imaging studies were reviewed to collect data on patient and lesion characteristics, and outcomes. Cancer incidence with 95% confidence interval (CI) was calculated.

RESULTS: This study included 71 women (median age 49 years) with 81 enhancing CEM lesions who underwent short-term follow-up CEM (median 6.2 months) after MRI reported no correlate. Of 81 lesions (median size = 0.7 cm), 73 (90%) were non-mass enhancement and 8 (10%) were enhancing masses. No sonographic correlate was identified for 75 lesions that had a same-day targeted ultrasound. Two cancers (2.5%, 95% CI 0.3-8.6) were diagnosed during the short-term follow-up period, one at 6-months (invasive ductal carcinoma) and one at 12-months (ductal carcinoma in situ). The remaining 79 lesions were benign at 6-month follow-up CEM and at one-year mammographic follow-up.

CONCLUSIONS: Follow-up CEM of MRI-occult lesions is prudent and may be reasonable to perform at one-year given the low incidence of cancer detected at six-months (one of 81) in our small study sample.}, } @article {pmid37737015, year = {2023}, author = {Sijnesael, T and Richard, F and Rätze, MA and Koorman, T and Bassey-Archibong, B and Rohof, C and Daniel, J and Desmedt, C and Derksen, PW}, title = {Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.}, journal = {The Journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1002/path.6205}, pmid = {37737015}, issn = {1096-9896}, support = {2018NovPCC1297/BBC_/Breast Cancer Now/United Kingdom ; }, abstract = {Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid37734568, year = {2023}, author = {Deberti, M and Goupille, C and Arbion, F and Vilde, A and Body, G and Ouldamer, L}, title = {Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {}, number = {}, pages = {102665}, doi = {10.1016/j.jogoh.2023.102665}, pmid = {37734568}, issn = {2468-7847}, abstract = {BACKGROUND: Axillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma.

OBJECTIVES: our study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma.

METHODS: This is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Centre of Tours between January 1, 2007 and December 31, 2018. The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659 RESULTS: Our study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94% for N0 patients, 92.4% for low-risk patients, 85.6% for intermediate-risk patients and 58.5% for high-risk patients. The 5-year distant metastasis-free survival was 98.2% for N0 patients, 95.9% for low-risk patients, 80.1% for intermediate-risk patients, and 60.3% for high-risk patients. Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors . However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival.

CONCLUSION: Our study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.}, } @article {pmid37731440, year = {2023}, author = {Okubo, T and Minari, Y and Ikura, Y}, title = {Change in Main Histological Type of Invasive Breast Cancer From Ductal to Lobular Carcinoma by Neoadjuvant Chemotherapy.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43816}, pmid = {37731440}, issn = {2168-8184}, abstract = {We present a case study of breast cancer initially diagnosed as invasive ductal carcinoma (IDC), which subsequently substituted into invasive lobular carcinoma (ILC) following neoadjuvant chemotherapy (NAC). A 61-year-old woman presented with a palpable breast lump, and histological examination through core needle biopsy (CNB) confirmed the presence of IDC. After a 6-month course of NAC, the patient achieved a clinically complete response (cCR) and underwent mastectomy. The surgical specimen showed no detectable tumor upon palpation, but microscopic analysis revealed a highly infiltrative growth of poorly-cohesive small atypical cells in the original tumor area. Immunohistochemical staining demonstrated that the tumor cells were negative for E-cadherin, leading to a diagnosis of ILC. To address the histological discrepancy before and after NAC, we re-evaluated the initial CNB using E-cadherin immunohistochemistry. While most tumor cells were E-cadherin positive, a small area displaying scirrhous subtype-like morphology exhibited E-cadherin negativity. Consequently, we revised the diagnosis to mixed IDC-ILC. The differential chemosensitivity between IDC and ILC may provide insight into this phenomenon.}, } @article {pmid37729354, year = {2023}, author = {Ferreira, CJDS and Caires, IQS and Costa Neto, WJBD and Almeida, SMV}, title = {Collagen content and C-X-C motif chemokine ligand 12 expression in neoplastic breast stroma.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {69}, number = {9}, pages = {e20221210}, pmid = {37729354}, issn = {1806-9282}, mesh = {Adolescent ; Adult ; Female ; Humans ; *Breast Neoplasms ; *Carcinoma, Ductal ; Collagen ; Ligands ; Mastectomy ; Receptors, Chemokine ; Retrospective Studies ; Tumor Microenvironment ; }, abstract = {OBJECTIVE: This study aimed to evaluate the expression of C-X-C motif chemokine ligand 12 and its C-X-C chemokine receptor type 4, and the tumor-stroma ratio using collagen stromal content of breast cancer samples, correlating it with clinicopathological data.

METHODS: Through a retrospective cohort study, samples were obtained from female patients, over 18 years of age, with the disease in stages 1-4, who underwent mastectomy or lumpectomy. The biopsies were provided by the Oncology sector of the Hospital das Clínicas of Universidade Federal de Pernambuco, Recife city, in 2011-2014, including samples of invasive ductal carcinoma, ductal carcinoma in situ, or benign changes (fibroadenoma and hypertrophy), which were analyzed between 2020 and 2022 by immunohistochemistry for the expression of stromal cell characteristics. Collagen content was tested by Gomori staining and digital analysis of images.

RESULTS: Absence of stromal expression of C-X-C motif chemokine ligand 12 was associated with longer disease-free survival (disease-free survival=0.481), and expression of C-X-C chemokine receptor type 4 was associated with lower disease-free survival. An association was observed between clinicopathological variables and stromal expression of chemokines, that is, an association of stromal C-X-C motif chemokine ligand 12 with histological grade, angiolymphatic invasion, and an association between C-X-C chemokine receptor type 4 expression and histological grade. Analyses of digital pixels images of collagen and tumor cells showed a lower percentage of collagen in the invasive ductal carcinoma samples (39%), unlike samples without neoplasms (78%).

CONCLUSION: Low expression of C-X-C motif chemokine ligand 12 may be associated with a worse prognosis for breast cancer. Collagen staining analyzed using digital images represents an opportunity for clinical application and is indicative of the prognosis of the tumor microenvironment in breast carcinoma.}, } @article {pmid37724141, year = {2023}, author = {Rezaei, A and Shayan, N and Shirazinia, S and Mollazadeh, S and Ghiyasi-Moghaddam, N}, title = {The Prognostic Significance of P16 Immunohistochemical Expression Pattern in Women with Invasive Ductal Breast Carcinoma.}, journal = {Reports of biochemistry & molecular biology}, volume = {12}, number = {1}, pages = {83-91}, pmid = {37724141}, issn = {2322-3480}, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women worldwide. The p16 protein is a cell cycle regulator and tumor suppressor implicated in several types of cancers. However, its relationship to breast cancer is still unknown. The present study aimed to assess the association of p16 protein expression with clinicopathological features in breast cancer.This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

METHODS: The study enrolled 100 patients with invasive ductal carcinoma. The samples were collected before any adjuvant chemotherapy, and p16 protein expression was determined using immunohistochemistry. Clinicopathological features were obtained from the patient's medical records.

RESULTS: Our findings demonstrated that p16 protein expression increased in estrogen receptor-positive tumor tissues (P< 0.01). However, no significant correlation was found between the p16 protein expression and the other clinicopathological features.

CONCLUSIONS: Our study demonstrated that p16 protein expression increased in ER-positive tumor tissue from patients with invasive ductal breast carcinoma. However, no correlation was found between the p16 protein expression and the other clinicopathological features.}, } @article {pmid37705411, year = {2023}, author = {McMurtry, V and Cleary, AS and Ruano, AL and Lomo, L and Gulbahce, HE}, title = {Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.}, journal = {American journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1097/COC.0000000000001041}, pmid = {37705411}, issn = {1537-453X}, abstract = {OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.

CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.}, } @article {pmid37697863, year = {2023}, author = {Lu, D and Li, F and Zhao, C and Ye, Y and Zhang, X and Yang, P and Zhang, X}, title = {A Remineralizing and Antibacterial Coating for Arresting Caries.}, journal = {Journal of dental research}, volume = {}, number = {}, pages = {220345231189992}, doi = {10.1177/00220345231189992}, pmid = {37697863}, issn = {1544-0591}, abstract = {Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.}, } @article {pmid37697031, year = {2023}, author = {Onega, T and Abraham, L and Miglioretti, DL and Lee, CI and Henderson, LM and Kerlikowske, K and Tosteson, ANA and Weaver, D and Sprague, BL and Bowles, EJA and di Florio-Alexander, RM}, title = {Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, pmid = {37697031}, issn = {1573-7217}, support = {U54CA163303/CA/NCI NIH HHS/United States ; P01 CA154292/CA/NCI NIH HHS/United States ; PCS-1504-30370/PCORI/Patient-Centered Outcomes Research Institute/United States ; P01CA154292/CA/NCI NIH HHS/United States ; R50CA211115/CA/NCI NIH HHS/United States ; R01CA149365/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population.

METHODS: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium. Examinations were followed for one year to ascertain incident ILC, IDC, or IMC. We measured cancer detection rate (CDR) and interval invasive cancer rate/1000 screening examinations for each histological subtype and stratified by breast density and modality. We calculated relative risk (RR) for DM vs. DBT using log-binomial models to adjust for the propensity of receiving DBT vs. DM.

RESULTS: Unadjusted CDR per 1000 mammograms of ILC overall was 0.33 (95%CI: 0.30-0.36) for DM; 0.45 (95%CI: 0.39-0.52) for DBT, and for women with dense breasts- 0.33 (95%CI: 0.29-0.37) for DM and 0.54 (95%CI: 0.43-0.66) for DBT. Similar results were noted for IDC and IMC. Adjusted models showed a significantly increased RR for cancer detection with DBT compared to DM among women with dense breasts for all three histologies (RR; 95%CI: ILC 1.53; 1.09-2.14, IDC 1.21; 1.02-1.44, IMC 1.76; 1.30-2.38), but no significant increase among women with non-dense breasts.

CONCLUSION: DBT was associated with higher CDR for ILC, IDC, and IMC for women with dense breasts. Early detection of ILC with DBT may improve outcomes for this distinct clinical entity.}, } @article {pmid37696743, year = {2023}, author = {Bernardino, RM and Sayyid, RK and Lajkosz, K and Al-Daqqaq, Z and Cockburn, JG and Chavarriaga, J and Abedi, S and Leão, R and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2023.08.010}, pmid = {37696743}, issn = {2405-4569}, abstract = {BACKGROUND: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions.

OBJECTIVE: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples.

Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study.

We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC.

RESULTS AND LIMITATIONS: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36-49%) for detection of cribriform morphology and 44.1% (95% CI 36-52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47-58%). Among patients who underwent multiparametric magnetic resonance imaging-guided biopsies, the sensitivity was 54% (95% CI 39-68%) for detection of cribriform morphology and 37% (95% CI 19-58%) for detection of IDC.

CONCLUSIONS: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed.

PATIENT SUMMARY: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.}, } @article {pmid37694008, year = {2023}, author = {Tanpure, VR and Palagiri, FB and Kolhe, KK and Wajekar, NA and Pathak, SS and Tanpure, AV and Kumar, A and Badiyani, BK}, title = {A Study to Assess Indian Patients' Expectations of Check-Up and Diagnosis or Discussion about Treatment at their Initial Orthodontic Visit.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {15}, number = {Suppl 2}, pages = {S1253-S1256}, pmid = {37694008}, issn = {0976-4879}, abstract = {AIM: To access the patient's expectations of orthodontic treatment at the first visit.

MATERIALS AND METHODS: Three hundred new patients to the orthodontics department were included in the analysis. Their demographic details and their opinions on what they hoped to gain from orthodontic treatment were gleaned from their replies to a well-crafted questionnaire.

RESULTS: Most respondents were more concerned with the cosmetic results of orthodontic treatment than they were with the therapy's practical benefits. They hoped that after having their teeth straightened, they would feel more comfortable interacting with others and have a better overall appearance. In terms of improving one's job and making one's speaking simpler, the mean scores were the lowest. The female participants averaged higher marks than the male participants across all areas studied, with the greatest mark coming in the area of improved smiles.

CONCLUSION: An effective outcome from orthodontic therapy requires full patient participation. Before beginning treatment, it is important for the orthodontist and patient to have an agreement on the patient's reasonable expectations for the therapy's outcomes.}, } @article {pmid37688253, year = {2023}, author = {Yang, SY and Kang, DS and Lee, CY}, title = {Coloration on Bluish Alginate Films with Amorphous Heterogeneity Thereof.}, journal = {Polymers}, volume = {15}, number = {17}, pages = {}, pmid = {37688253}, issn = {2073-4360}, support = {2019R1I1A3A01060180//National Research Foundation of Korea/ ; 2021R1A5A1031868//National Research Foundation of Korea/ ; }, abstract = {Using sodium alginate (Alg) aqueous solution containing indigo carmine (IdC) at various concentrations we characterized the rippled surface pattern with micro-spacing on a flexible film as intriguing bluish Alg-IdC iridescence. The characterization was performed using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, field emission scanning electron microscopy, atomic force microscopy, electron microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction analysis, and photoluminescence detection. The edge pattern on the film had a maximum depth of 825 nm, a peak-to-peak distance of 63.0 nm, and an average distance of 2.34 nm. The center of the pattern had a maximum depth of 343 nm and a peak-to-peak distance of 162 nm. The pattern spacing rippled irregularly, widening toward the center and narrowing toward the edges. The rippled nano-patterned areas effectively generated iridescence. The ultraviolet absorption spectra of the mixture in the 270 and 615 nm ranges were the same for both the iridescent and non-iridescent film surfaces. By adding Ag[+] ions to Alg-IdC, self-assembled microspheres were formed, and conductivity was improved. Cross-linked bluish materials were immediately formed by the addition of Ca[2+] ions, and the film was prepared by controlling their concentration. This flexible film can be used in applications such as eco-friendly camouflage, anti-counterfeiting, QR code materials for imaging/sensing, and smart hybrid displays.}, } @article {pmid37686673, year = {2023}, author = {Timbres, J and Kohut, K and Caneppele, M and Troy, M and Schmidt, MK and Roylance, R and Sawyer, E}, title = {DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?.}, journal = {Cancers}, volume = {15}, number = {17}, pages = {}, pmid = {37686673}, issn = {2072-6694}, abstract = {Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35-60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT.}, } @article {pmid37684268, year = {2023}, author = {Zhao, F and Zhang, T and Sun, X and Zhang, X and Chen, L and Wang, H and Li, J and Fan, P and Lai, L and Sui, T and Li, Z}, title = {A strategy for Cas13 miniaturization based on the structure and AlphaFold.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5545}, pmid = {37684268}, issn = {2041-1723}, mesh = {*Dependovirus ; *Endonucleases ; Miniaturization ; RNA ; RNA Editing ; }, abstract = {The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.}, } @article {pmid37683019, year = {2023}, author = {Moon, SY and Lim, KR and Son, JS}, title = {The role of infectious disease consultations in the management of patients with fever in a long-term care facility.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0291421}, pmid = {37683019}, issn = {1932-6203}, mesh = {Humans ; Long-Term Care ; Retrospective Studies ; Nursing Homes ; Fever ; Referral and Consultation ; Tertiary Care Centers ; *Cardiomyopathy, Dilated ; *Communicable Diseases/therapy ; }, abstract = {BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.

METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.

RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8±0.6°C vs. 38.6±0.5°C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.

CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.}, } @article {pmid37682691, year = {2023}, author = {Goh, SSN and Syn, NLX and Lim, CJE and Lee, RE and Samuel, M and Ng, CWQ}, title = {Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.}, journal = {The British journal of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjs/znad199}, pmid = {37682691}, issn = {1365-2168}, abstract = {BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast.

METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy.

RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20).

CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.}, } @article {pmid37681174, year = {2023}, author = {Wang, W and Ge, J and Ma, H and Lian, H and Cui, L and Zhao, Y and Li, Z and Wang, T and Zhang, R}, title = {Cladribine and cytarabine in children refractory high risk multisystem Langerhans cell histiocytosis.}, journal = {Heliyon}, volume = {9}, number = {9}, pages = {e19277}, pmid = {37681174}, issn = {2405-8440}, abstract = {There is no uniform regimen for refractory Langerhans cell histiocytosis (LCH). We retrospectively described patients with refractory multisystem and risk organ involvement LCH treated with the low-dose (Ara-c, 100 mg/m[2]/d × 5day; 2-CDA, 5 mg/m[2]/d × 5day) chemotherapy (LDC) and the intermediate-dose (Ara-c, 500 mg/m[2]/d × 5day; 2-CDA, 9 mg/m[2]/d × 5day) chemotherapy (IDC). 26 patients and 10 patients receiving the LDC and IDC regimen from January 2013 to December 2016 were included in the study. The overall response rate exhibited no significant difference between the LDC and IDC groups after four courses (76.9% vs 90%, P = 0.375) and eight courses (80.8% vs 100%, P = 0.135) of treatment. No statistical differences in the overall survival rate were observed between the two groups, but 5-year event-free survival rate of patients in the IDC group was higher than that in the LDC group at the median follow-up of 6.16 and 5.07 years (88.9% vs 52.9%, P = 0.033). The patients in the IDC group had more severe myelosuppression than those in the LDC group (grade 3/4 myelosuppression, 80% vs 19.2%, P = 0.001). The intermediate-dose regimen of 2CDA and Ara-c had a higher event-free survival rate and a similar overall survival rate compared with the low-dose regimen.}, } @article {pmid37673327, year = {2023}, author = {Mudeng, V and Farid, MN and Ayana, G and Choe, SW}, title = {Domain and Histopathology Adaptations-Based Classification for Malignancy Grading System.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2023.07.007}, pmid = {37673327}, issn = {1525-2191}, abstract = {Through accurate proliferation rate quantification, an appropriate treatment for breast cancer may be devised. Pathologists use breast tissue biopsy glass slides stained with hematoxylin and eosin to obtain grading information. However, this manual evaluation may lead to high costs and ineffectiveness because diagnosis depends on the facility and the pathologists' insights and experiences. A convolutional neural network is considered feasible as a computer-based observer to improve clinicians' capacity in grading breast cancer. Therefore, this study proposes a novel scheme for automatic breast cancer malignancy grading from invasive ductal carcinoma. The proposed classifiers implement multistage transfer learning incorporating domain and histopathologic transformations. Domain adaptation using pretrained models, such as InceptionResNetV2, InceptionV3, NASNet-Large, ResNet50, ResNet101, VGG19, and Xception, was applied to classify the ×40 magnification BreaKHis data set into eight classes. Then, the best models, in this study, InceptionV3 and Xception, which contain the domain and histopathology pretrained weights, were used to categorize the Databiox database into grades 1, 2, or 3. To provide a comprehensive report, this study offers a patchless automated grading system for magnification-dependent and magnification-independent classifications. With an overall accuracy (means ± SD) of 90.17% ± 3.08% to 97.67% ± 1.09% and an F1 score of 0.9013 to 0.9760 for magnification-dependent classification, the classifiers in this work achieved outstanding performance. The proposed approach could be used for breast cancer grading systems in clinical settings.}, } @article {pmid37671834, year = {2023}, author = {Giroud, M and Kotschi, S and Kwon, Y and Le Thuc, O and Hoffmann, A and Gil-Lozano, M and Karbiener, M and Higareda-Almaraz, JC and Khani, S and Tews, D and Fischer-Posovszky, P and Sun, W and Dong, H and Ghosh, A and Wolfrum, C and Wabitsch, M and Virtanen, KA and Blüher, M and Nielsen, S and Zeigerer, A and García-Cáceres, C and Scheideler, M and Herzig, S and Bartelt, A}, title = {The obesity-linked human lncRNA AATBC stimulates mitochondrial function in adipocytes.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {e57600}, doi = {10.15252/embr.202357600}, pmid = {37671834}, issn = {1469-3178}, support = {//Helmholtz Zentrum München (Helmholtz Centre Munich, German Research Center for Environmental Health)/ ; //Alexander von Humboldt-Stiftung (AvH)/ ; FI1700/7#x2010;1//Deutsche Forschungsgemeinschaft (DFG)/ ; TE912/2#x2010;2//Deutsche Forschungsgemeinschaft (DFG)/ ; TRR205//Deutsche Forschungsgemeinschaft (DFG)/ ; SFB1123//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; //EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; }, abstract = {Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.}, } @article {pmid37668423, year = {2023}, author = {Amiri, A and Dietz, C and Rapp, A and Cardoso, MC and Stark, RW}, title = {The cyto-linker and scaffolding protein "plectin" mis-localization leads to softening of cancer cells.}, journal = {Nanoscale}, volume = {15}, number = {36}, pages = {15008-15026}, doi = {10.1039/d3nr02226a}, pmid = {37668423}, issn = {2040-3372}, mesh = {Humans ; *Carcinoma, Ductal/metabolism ; Cytoplasm/metabolism ; Cytoskeleton/metabolism ; Hydrolases/metabolism ; Microtubules/metabolism ; }, abstract = {Discovering tools to prevent cancer progression requires understanding the fundamental differences between normal and cancer cells. More than a decade ago, atomic force microscopy (AFM) revealed cancer cells' softer body compared to their healthy counterparts. Here, we investigated the mechanism underlying the softening of cancerous cells in comparison with their healthy counterparts based on AFM high resolution stiffness tomography and 3D confocal microscopy. We showed microtubules (MTs) network in invasive ductal carcinoma cell cytoskeleton is basally located and segmented for around 400 nm from the cell periphery. Additionally, the cytoskeleton scaffolding protein plectin exhibits a mis-localization from the cytoplasm to the surface of cells in the carcinoma which justifies the dissociation of the MT network from the cell's cortex. Furthermore, the assessment of MTs' persistence length using a worm-like-chain (WLC) model in high resolution AFM images showed lower persistence length of the single MTs in ductal carcinoma compared to that in the normal state. Overall, these tuned mechanics support the invasive cells to ascertain more flexibility under compressive forces in small deformations. These data provide new insights into the structural origins of cancer aids in progression.}, } @article {pmid37665386, year = {2023}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Correction: Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00702-023-02690-x}, pmid = {37665386}, issn = {1435-1463}, } @article {pmid37664269, year = {2023}, author = {Haque, E and Mushtaq, AH and Alkhatib, R and Alhusaini, H and Suleman, K}, title = {An Unexpected Diagnosis of Second Primary Malignancy in a Breast Cancer Survivor: A Case Report.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e42819}, pmid = {37664269}, issn = {2168-8184}, abstract = {BACKGROUND: Breast cancer survival rates are increasing more than ever with the development of better diagnostic and therapeutic techniques. Survivors of breast cancer have an increased risk of developing second primary malignancies, which may be mistaken for breast cancer recurrence and lead to delayed diagnosis and poor prognosis.

CASE REPORT: We report a case of a 62-year-old female who presented with shortness of breath and bone pain. She had a history of left triple-positive invasive ductal carcinoma (T1N0M0) treated with bilateral skin-sparing mastectomy, adjuvant Taxotere, and trastuzumab-based therapy and then continued on trastuzumab and letrozole. She underwent imaging to explore the source of her symptoms at which new pulmonary nodules were discovered. During workup, she was found to have elevated tumor markers. They were initially suspected to be breast cancer recurrence metastases based on elevated tumor markers; however, further investigations confirmed that the nodules were a second primary lung adenocarcinoma with a different molecular profile. The patient had disease progression despite chemotherapy and eventually succumbed to her disease.

CONCLUSION: This case highlights the importance of considering second primary malignancies in breast cancer survivors and utilizing advanced diagnostic modalities to efficiently diagnose such cases.}, } @article {pmid37661085, year = {2023}, author = {Park, SY and Kim, HJ and Lee, J and Jeong, JY and Byun, J and Kim, WH and Park, B and Hong, J}, title = {A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report.}, journal = {Journal of breast cancer}, volume = {26}, number = {4}, pages = {397-402}, pmid = {37661085}, issn = {1738-6756}, abstract = {Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.}, } @article {pmid37649292, year = {2023}, author = {Ramli Hamid, MT and Loi, KS and Chan, WY and Ab Mumin, N and Abdul Hamid, S and Izza Rozalli, F and Rahmat, K}, title = {Clinical usefulness of abbreviated mri protocol in breast cancer detection.}, journal = {Current medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.2174/1573405620666230829150218}, pmid = {37649292}, issn = {1573-4056}, abstract = {BACKGROUND: The use of breast MRI for screening has increased over the past decade, mostly in women with a high risk of breast cancer. Abbreviated breast MRI (AB-MR) is introduced to make MRI a more accessible screening modality. AB-MR decreases scanning and reporting time and the overall cost of MRI.

OBJECTIVE: This study aims to evaluate the diagnostic efficacy of abbreviated MRI protocol in detecting breast cancer in screening and diagnostic populations, using histopathology as the reference standard.

MATERIALS AND METHODS: This is a single-centre retrospective cross-sectional study of 134 patients with 198 histologically proven breast lesions who underwent full diagnostic protocol contrast-enhanced breast MRI (FDP-MR) at the University Malaya Medical Centre (UMMC) from 1st January 2018 to 31st December 2019. AB-MR was pre-determined and evaluated with regard to the potential to detect and exclude malignancy from 3 readers of varying radiological experiences. The sensitivity of both AB-MR and FDP-MR were compared using the McNemar test, where both protocols' diagnostic performances were assessed via the receiver operating characteristic (ROC) curve. Inter-observer agreement was analysed using Fleiss Kappa.

RESULT: There were 134 patients with 198 lesions. The average age was 50.9 years old (range 27 - 80). A total of 121 (90%) MRIs were performed for diagnostic purposes. Screening accounted for 9.4% of the cases, 55.6% (n=110) lesions were benign, and 44.4% (n=88) were malignant. The commonest benign and malignant lesions were fibrocystic change (27.3%) and invasive ductal carcinoma (78.4%). The mean sensitivity, specificity, positive predictive value, and negative predictive value for AB-MR were 0.96, 0.57, 0.68 and 0.94, respectively. Both AB-MR and FDP-MR showed excellent diagnostic performance with AUC of 0.88 and 0.96, respectively. The general inter-observer agreement of all three readers for AB-MR was substantial (k=0.69), with fair agreement demonstrated between AB-MR and FDP-MR (k=0.36).

CONCLUSION: The study shows no evidence that the diagnostic efficacy of AB-MR is inferior to FDP-MR. AB-MR, with high sensitivity, has proven its capability in cancer detection and exclusion, especially for biologically aggressive cancers.}, } @article {pmid37648809, year = {2023}, author = {Miljanic, M and Nwachukwu, C and Rahimi, A}, title = {Definitive ablative stereotactic partial breast irradiation in early stage inoperable breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37648809}, issn = {1432-1335}, abstract = {PURPOSE: This case series and literature review aims to investigate the efficacy and safety of definitive ablative radiation therapy as a treatment modality for non-operable patients with early stage breast cancer. We present two cases demonstrating the potential of this approach to achieve durable responses.

METHODS: We assessed the long-term response of two non-operable patients diagnosed with Stage II (cT2N0M) and Stage IA (T1bN0M0) invasive ductal carcinoma (IDC), who were deemed unfit for surgery due to significant co-morbid conditions. Definitive ablative radiation therapy was administered using stereotactic partial breast irradiation with ablative doses delivered in either a single fraction or two fractions. Serial imaging was conducted to assess treatment response and monitor adverse events.

RESULTS: Both patients exhibited notable treatment responses following definitive ablative radiation therapy. The first patient, an 84-year-old woman, experienced a 69% reduction in tumor size over a follow-up period exceeding 2 years. The second patient, an 87-year-old woman, achieved complete resolution of disease on imaging, with no signs of progression even 26 month post-treatment. Both patients tolerated the treatment well, without significant treatment-related adverse events.

CONCLUSIONS: Our case series suggests that definitive ablative radiation therapy may serve as a safe and effective treatment option for non-operable patients with early stage breast cancer. The observed durable treatment responses and minimal toxicity support the potential of this approach. Furthermore, a longer interval between ablative radiation therapy and surgery may enhance treatment response, potentially leading to increased complete pathologic response rates.}, } @article {pmid37637763, year = {2023}, author = {Abbasi, A and Ghaffarizadeh, F and Mojdeganlou, H}, title = {Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {17}, number = {2}, pages = {100-105}, pmid = {37637763}, issn = {2008-3009}, abstract = {Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.}, } @article {pmid37635979, year = {2023}, author = {Barlier, A and Romanet, P and Pellegata, NS}, title = {Editorial: New insights into multiple endocrine neoplasia type 1.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1266148}, pmid = {37635979}, issn = {1664-2392}, mesh = {Humans ; *Multiple Endocrine Neoplasia Type 1/genetics ; }, } @article {pmid37624596, year = {2023}, author = {Liu, G and Kong, X and Dai, Q and Cheng, H and Wang, J and Gao, J and Wang, Y}, title = {Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.}, journal = {JAMA network open}, volume = {6}, number = {8}, pages = {e2331078}, pmid = {37624596}, issn = {2574-3805}, mesh = {Female ; Humans ; Male ; Middle Aged ; Asian People ; *Breast Neoplasms/surgery ; Cohort Studies ; Lymphatic Metastasis ; Mastectomy ; Prognosis ; Receptor, ErbB-2/chemistry ; }, abstract = {IMPORTANCE: Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery.

OBJECTIVE: To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach.

This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023.

MAIN OUTCOMES AND MEASURES: Patients' OS and DFS.

RESULTS: The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC.

CONCLUSIONS AND RELEVANCE: This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.}, } @article {pmid37621419, year = {2023}, author = {Dao, E and Gohla, G and Williams, P and Lovrics, P and Badr, F and Fang, Q and Farrell, TJ and Farquharson, MJ}, title = {Multivariate analysis of breast tissue using optical parameters extracted from a combined time-resolved fluorescence and diffuse reflectance system for tumor margin detection.}, journal = {Journal of biomedical optics}, volume = {28}, number = {8}, pages = {085001}, pmid = {37621419}, issn = {1560-2281}, mesh = {Humans ; Multivariate Analysis ; *Breast/diagnostic imaging ; Mastectomy, Segmental ; Obesity ; *Optical Devices ; Radiopharmaceuticals ; }, abstract = {SIGNIFICANCE: Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system.

AIM: A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making.

APPROACH: Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets.

RESULTS: The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification.

CONCLUSION: The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.}, } @article {pmid37610487, year = {2023}, author = {Barker, VR and Naffouje, SA and Mallory, MA and Hoover, SA and Laronga, C}, title = {Surgical Management of the Axilla in HR+/HER2- Breast Cancer in the Z1071 Era: A Propensity Score-Matched Analysis of the National Cancer Database.}, journal = {Annals of surgical oncology}, volume = {}, number = {}, pages = {}, pmid = {37610487}, issn = {1534-4681}, abstract = {BACKGROUND: Axillary management varies between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) for patients with clinical N1 (cN1), hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)/neu-negative (HER2-), infiltrative ductal carcinoma (IDC) who achieve a complete clinical response (cCR) to neoadjuvant systemic therapy (NAST). This study sought to evaluate clinical practice patterns and survival outcomes of SLNB versus ALND in this patient subset.

METHODS: Patients with cN1, HR+/HER2-, unilateral IDC demonstrating a cCR to NAST were identified from the 2012-2017 National Cancer Database (NCDB) and stratified based on final axillary surgery management (SLNB vs ALND). After propensity score-matching, overall survival (OS) was compared using a Kaplan-Meier analysis, and significant OS predictors were identified using Cox regression.

RESULTS: Of the 1676 patients selected for this study, 593 (35.4%) underwent SLNB and 1083 (64.6%) underwent ALND. Use of SLNB increased by 28 % between 2012 and 2017. Among a total of 584 matched patients, 461 matched ypN0 patients, and 108 matched ypN+ patients, mean OS did not differ between SLNB and ALND (all patients [92.1 ± 0.8 vs 90.2 ± 1.0 months; p = 0.157], ypN0 patients [92.4 ± 0.8 vs 89.9 ± 0.9 months; p = 0.105], ypN+ patients [83.5 ± 2.3 vs 91.7 ± 2.7 months; p ± 0.963). Cox regression identified age, Charlson score, clinical T stage, and pathologic nodal status as significant predictors of OS.

CONCLUSION: The final surgical management strategy used for cN1, HR+/HER2- IDC patients who achieved a cCR to NAST did not have a significant impact on survival outcomes in this analysis. Potential opportunities for de-escalation of axillary management among this patient subset exist, and validation studies are needed.}, } @article {pmid37608749, year = {2023}, author = {Ito, T and Takahara, T and Taniguchi, N and Yamamoto, Y and Satou, A and Ohashi, A and Takahashi, E and Sassa, N and Tsuzuki, T}, title = {PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.}, journal = {Pathology international}, volume = {}, number = {}, pages = {}, doi = {10.1111/pin.13369}, pmid = {37608749}, issn = {1440-1827}, support = {21K06933//Japan Society for the Promotion of Science/ ; 21K15392//Japan Society for the Promotion of Science/ ; }, abstract = {Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.}, } @article {pmid37605516, year = {2023}, author = {Wang, Y and Liang, Y and Ye, F and Luo, D and Jin, Y and Li, Y and Zhao, W and Chen, B and Wang, L and Yang, Q}, title = {Histologic heterogeneity predicts patient prognosis of HER2-positive metastatic breast cancer: A retrospective study based on SEER database.}, journal = {Cancer medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/cam4.6469}, pmid = {37605516}, issn = {2045-7634}, support = {2020SDUCRCA015//Foundation from Clinical Research Center of Shandong University/ ; 2020YFA0712400//National Key Research and Development Program/ ; 2019-3//Qilu Hospital Clinical New Technology Developing Foundation/ ; ts20190971//Special Foundation for Taishan Scholars/ ; }, abstract = {BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC.

METHODS: HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods.

RESULTS: A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy.

CONCLUSIONS: Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.}, } @article {pmid37602185, year = {2023}, author = {Amritanand, A and Arthur, A and Horo, S and Obed, P and Ramamurthy, P and Rebekah, G and Abraham, VJ and Paul, P}, title = {Comparative evaluation of diabetic retinopathy screening programs in regular ophthalmology clinics versus integrated diabetic clinics within rural health-care services.}, journal = {Oman journal of ophthalmology}, volume = {16}, number = {2}, pages = {237-243}, pmid = {37602185}, issn = {0974-620X}, abstract = {BACKGROUND: Robust integration of diabetic retinopathy (DR) screening within health systems is essential to prevent DR-related blindness. This, however, remains a challenge in the developing world. The aim of this study was to evaluate two models of DR screening programs within rural general health-care services.

MATERIALS AND METHODS: This was a retrospective observational study from two rural health centers. Demographic and clinical data of patients completing DR screening were analyzed. Patients were screened in regular ophthalmology clinics (ROC) or integrated diabetic clinics (IDC). Referral and treatment completion data were retrieved from the clinical charts at the base hospital.

RESULTS: A total of 2535 DR screenings were conducted for 2296 patients. The total population prevalence for any DR was 14.2% (95% confidence interval [CI]: 12.8%-15.6%) and vision-threatening DR (VTDR) was 4.7% (95% CI: 3.8%-5.6%). In the ROC and IDC groups, respectively, the prevalence of any DR was 20.4% and 8.2%, VTDR, 7.8% and 1.7%, and blindness, 1.4% and 0.4% (all P < 0.001). Referral completion rates were higher in the ROC group (44.8% vs. 25.2%, P < 0.001), while treatment completion in both was similar (69.6% vs. 70.6%). Referral and treatment completion rates for referable DR were 61.2% and 48.2%, and for VTDR, 62% and 38.8%, respectively. Only 11.45% of patients completed the repeat screening follow-up.

CONCLUSIONS: Patients attending IDCs had a significantly lower prevalence of any DR, VTDR, and blindness demonstrating the advantages of integrated diabetic care in a rural setting. However, referral uptake and DR treatment completion need strengthening.}, } @article {pmid37602036, year = {2023}, author = {Ayandipo, O and Ajagbe, O and Afolabi, A and Ogundiran, T and Orunmuyi, A and Soneye, O}, title = {Venous Thromboembolism in Hospitalized Patients With Surgical Breast Cancer: Risks and Outcomes.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42096}, pmid = {37602036}, issn = {2168-8184}, abstract = {Background The Caprini risk assessment model has been validated in breast cancer surgery patients. However, its utility in our population has not been described. This study evaluated the benefits and risks of the Caprini risk stratification tool and the incidence of venous thromboembolism (VTE) in the 30-day postoperative period among surgical female patients with breast cancer who were hospitalized during their treatment. Methodology This is a retrospective review of prospectively collected data of all surgical patients with histologically confirmed breast cancer who were hospitalized between January and December 2018. Caprini score, treatment information, and 30-day outcome of prophylaxis were collated and analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results A total of 167 female patients with breast cancer aged 19 to 75 years were hospitalized during the study period. All patients had invasive ductal carcinoma, and the majority (76.6%) were premenopausal. Two fatal VTE events occurred during hospitalization, giving a 30-day incidence of 1.2%. There was no adverse event from chemoprophylaxis. Conclusions VTE is rare in hospitalized surgical patients with breast cancer undergoing routine pharmacologic and mechanical prophylaxis. The Caprini tool can identify extremely low-risk patients who require no prophylaxis.}, } @article {pmid37601676, year = {2023}, author = {Liu, G and Xing, Z and Guo, C and Dai, Q and Cheng, H and Wang, X and Tang, Y and Wang, Y}, title = {Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1217869}, pmid = {37601676}, issn = {2234-943X}, abstract = {OBJECTIVES: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS).

MATERIALS AND METHODS: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model.

RESULTS: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients.

CONCLUSION: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.}, } @article {pmid37596340, year = {2023}, author = {Aftab, A and Ahmad, B and Bashir, S and Rafique, S and Bashir, M and Ghani, T and Gul, A and Shah, AU and Khan, R and Sajini, AA}, title = {Comparative study of microscale and macroscale technique for encapsulation of Calotropis gigantea extract in metal-conjugated nanomatrices for invasive ductal carcinoma.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13474}, pmid = {37596340}, issn = {2045-2322}, mesh = {Silver ; Antioxidants/pharmacology ; *Calotropis ; *Metal Nanoparticles ; Plant Extracts/pharmacology ; *Carcinoma, Ductal ; }, abstract = {The encapsulation of plant extract in nanomatrices has limitations due to its adhesion to walls, size control, high cost and long durations that results in low yield. Macroscale and microscale level techniques for development of micro/nanoparticles may impact the encapsulation of plant extract. This study aimed to evaluate the relative efficiency of microscale and macroscale techniques for encapsulation of plant extract, which is not compared yet. Keeping this in view, encapsulation of Calotropis gigantea leaves extract (CaG) was attained in silver-conjugated poliglusam nanomatrices (POL/Ag) to induce apoptosis in invasive ductal carcinoma (IDC) cells. The ethanolic CaG extract was prepared using percolation method and characterized by chemical tests for its active phytochemical compounds. The droplet-based microfluidic system was utilized as microscale encapsulation technique for CaG in nanomatrices at two different aqueous to oil flow rate ratios 1.0:1.5, and 1.0:3.0. Moreover, conventional batch system was utilized as macroscale encapsulation technique consisted of hot plate magnetic stirrer. The prepared nanomatrices were analysed for antioxidant activity using DPPH test and for cytotoxicity analysis using MCF-7 cells. The characteristic peaks of UV-Vis, FTIR and XRD spectrum confirmed the synthesis of CaG(POL/Ag) by both the encapsulation methods. However, microfluidic system was found to be more expedient because of attaining small and uniform sized silver nanoparticles (92 ± 19 nm) at high flow rate and achieving high encapsulation efficiency (80.25%) as compared to the conventional batch method (52.5%). CaG(POL/Ag) nanomatrices found to have significant antioxidant activity (p = 0.0014) against DPPH radical scavenging activity. The CaG(POL/Ag) of the smallest sized formulated by the microfluidic system has also shown the highest cytotoxicity (90%) as compared to batch method (70%) at 80 µg/mL. Our results indicate that the microscale technique using microfluidic system is a more efficient method to formulate size-controlled CaG(POL/Ag) nanomatrices and achieve high encapsulation of plant extract. Additionally, CaG(Pol/Ag) was found to be an efficient new combination for inducing potent (p < 0.0001) apoptosis in IDC cells. Therefore, CaG(Pol/Ag) can be further tested as an anti-cancer agent for in-vivo experiments.}, } @article {pmid37595905, year = {2023}, author = {Hu, J and Effiong, K and Liu, M and Xiao, X}, title = {Broad spectrum and species specificity of plant allelochemicals 1,2-benzenediol and 3-indoleacrylic acid against marine and freshwater harmful algae.}, journal = {The Science of the total environment}, volume = {898}, number = {}, pages = {166356}, doi = {10.1016/j.scitotenv.2023.166356}, pmid = {37595905}, issn = {1879-1026}, mesh = {*Pheromones/toxicity ; Species Specificity ; *Harmful Algal Bloom ; Fresh Water ; }, abstract = {Allelochemicals derived from plants have shown great potential in mitigating harmful algal blooms (HABs), although different algal species can respond differently to these chemicals. Therefore, we first investigated the allelopathic effects of two newly identified plant-derived allelochemicals, 1,2-benzenediol (1,2-BD) and 3-indoleacrylic acid (3-IDC), on six algal species. Then we further evaluated the allelopathic responses of two bloom-forming species, Microcystis aeruginosa FACHB-905 and Heterosigma akashiwo to 1,2-BD. Results showed that 1,2-BD had a broader antialgal spectrum than 3-IDC. Allelopathic response analysis indicated that 1,2-BD consistently and stably inhibit the growth of M. aeruginosa FACHB-905, with inhibitory mechanism being disruption of photosynthetic activity, overwhelming of the antioxidant system and activation of programmed cell death (PCD). H. akashiwo displayed resistance to 1,2-BD during exposure, and the growth inhibition was mainly attributed to PCD. Therefore, the species-specific allelopathic responses provide new insights for controlling HABs using 1,2-BD and 3-IDC.}, } @article {pmid37592911, year = {2023}, author = {Rosa, C and Singh, P and Chen, P and Sinha, A and Claës, A and Preiser, PR and Dedon, PC and Baumgarten, S and Scherf, A and Bryant, JM}, title = {Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {e57090}, doi = {10.15252/embr.202357090}, pmid = {37592911}, issn = {1469-3178}, support = {MOE2018-T2-2-131//Academic Research Fund of the Ministry of Education, Singapore/ ; ANR-21-CE15-0010 PlasmoVarOrg//Agence Nationale de la Recherche (ANR)/ ; ANR-11-LABEX-0024-01 ParaFrap//Agence Nationale de la Recherche (ANR)/ ; //Alliance Française contre les Maladies Parasitaires (ParaFrap)/ ; PlasmoSilencing 670301//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; PlasmoEpiRNA 947819//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; EMBO ALTF 1444-2016//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 632-2018//European Molecular Biology Organization (EMBO)/ ; EMBO ALTF 180-2015//European Molecular Biology Organization (EMBO)/ ; //Institut Pasteur/ ; 6.11.18//Merlion Project/ ; //Ministry of Education, Singapore/ ; //National Research Foundation Singapore (NRF)/ ; }, abstract = {The complex life cycle of the human malaria parasite, Plasmodium falciparum, is driven by specific transcriptional programs, but it is unclear how most genes are activated or silenced at specific times. There is an association between transcription and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it has all core components of the cohesin complex. To investigate the role of cohesin in P. falciparum, we functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown during early stages of the intraerythrocytic developmental cycle (IDC) upregulates a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq analyses reveal that during the IDC, SMC3 enrichment at the promoter regions of these genes inversely correlates with gene expression and chromatin accessibility. These data suggest that SMC3 binding contributes to the repression of specific genes until their appropriate time of expression, revealing a new mode of stage-specific gene repression in P. falciparum.}, } @article {pmid37580403, year = {2023}, author = {Ishtiaq, A and Nasrullah, MA and Khan, JS and Malik, S and Tareen, U and Anees, M and Sultan, A and Murtaza, I}, title = {A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37580403}, issn = {1432-1335}, support = {HEC//Higher Education Commision, Pakistan/ ; URF//Quaid-i-Azam University/ ; }, abstract = {BACKGROUND: Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population.

METHODS: The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed.

RESULTS: The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level.

CONCLUSION: Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.}, } @article {pmid37579629, year = {2023}, author = {Bencherifi, Y and Watik, F and Lyafi, Y and Mostapha, B and Ennachit, M and Mohammed, EK}, title = {Mucinous carcinoma of the breast: Rare histological entity to know: About two cases and review of literature.}, journal = {International journal of surgery case reports}, volume = {110}, number = {}, pages = {108652}, pmid = {37579629}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Breast cancer is the first gynecological cancer in women, dominated by invasive ductal cancer . It is characterized by the presence of extracellular mucus, mucinous carcinoma represents one to 7 % of all invasive carcinomas and by a more favorable prognosis, Presentation of the case: We present two patients followed for an invasive mucinous carcinoma, CLINICAL DISCUSSION: Mucinous carcinoma of the breast is a rare entity. Therapeutic management does not differ from other histological types. It is based on surgery, chemotherapy and radiotherapy. Conservative treatment is recommended for T1, T2. Partial and accelerated irradiation of the breast is currently the most recommended after breast-conserving surgery.

CONCLUSION: Mucinous carcinoma is a rare histological entity with a favorable prognosis compared to other histological types. A benign-looking mass on imaging is not always reassuring, especially if it occurs in a woman over 60 years old. Since it can reveal colloid carcinoma.}, } @article {pmid37579325, year = {2023}, author = {Mooshage, CM and Tsilingiris, D and Schimpfle, L and Kender, Z and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Insulin resistance is associated with the capillary permeability of thigh muscles in patients with type 2 diabetes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgad481}, pmid = {37579325}, issn = {1945-7197}, abstract = {OBJECTIVE: Insulin-mediated microvascular permeability and blood flow of skeletal muscle appears to be altered in the condition of insulin resistance. Previous studies on this effect used invasive procedures in humans or animals. The aim of this study was to demonstrate the feasibility of a non-invasive assessment of human muscles' microcirculation via dynamic contrast-enhanced (DCE)-MRI of skeletal muscle in patients with type two diabetes (T2D).

METHODS: 56 participants (46 with T2D, 10 healthy controls, HC) underwent DCE-MRI of the right thigh at 3 Tesla. The constant of the musculature's microvascular permeability (Ktrans), extravascular extracellular volume fraction (ve), and plasma volume fraction (vp) were calculated.

RESULTS: In T2D patients, skeletal muscle Ktrans was lower (HC 0.0677 ± 0.002 min-1, T2D 0.0664 ± 0.002 min-1; p = 0.042) while the homeostasis model assessment (HOMA)-index was higher in patients with T2D compared to HC (HC 2.72 ± 2.2, T2D 6.11 ± 6.2; p = 0.011). In T2D, Ktrans correlated negatively with insulin (r = -0.39, p = 0.018) and HOMA-index (r = -0.38, p = 0.020).

CONCLUSION: The results signify that skeletal muscle DCE MRI can be employed as a non-invasive technique for the assessment of muscles' microcirculation in T2D. Our findings suggest that microvascular permeability of skeletal muscle is lowered in patients with T2D and that a decrease in microvascular permeability is associated with insulin resistance. These results are of interest with regards to the impact of muscle perfusion on diabetic complications such as diabetic sarcopenia.}, } @article {pmid37560809, year = {2023}, author = {Alfaro, AJ and Dittner, C and Becker, J and Loft, A and Mhamane, A and Maida, A and Georgiadi, A and Tsokanos, FF and Klepac, K and Molocea, CE and El-Merahbi, R and Motzler, K and Geppert, J and Karikari, RA and Szendrödi, J and Feuchtinger, A and Hofmann, S and Karaca, S and Urlaub, H and Berriel Diaz, M and Melchior, F and Herzig, S}, title = {Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {e55981}, doi = {10.15252/embr.202255981}, pmid = {37560809}, issn = {1469-3178}, support = {314061271//Deutsche Forschungsgemeinschaft (DFG)/ ; 329628492//Deutsche Forschungsgemeinschaft (DFG)/ ; A01//Deutsche Forschungsgemeinschaft (DFG)/ ; //Edith-Haberland-Wagner Stiftung/ ; 2020 EKSE.23//Else Köner-Fresenius-Stiftung (EKFS)/ ; ZT-0026//Helmholtz Gemeinschaft/ ; //DKFZ-ZMBH Alliance/ ; //Open Access funding enabled and organized by Projekt DEAL/ ; }, abstract = {Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.}, } @article {pmid37559588, year = {2023}, author = {Bai, X and Fang, C and Liu, B and Huagn, J and Chen, X and Xie, X and Zhang, Q and Liu, M and Liang, J and Guo, J and Song, L and Lan, X and Chen, L and Huang, S and Deng, W and Luo, Z and Du, C}, title = {Breast cancer metastases to the thyroid and stomach: A case report.}, journal = {Oncology letters}, volume = {26}, number = {3}, pages = {386}, pmid = {37559588}, issn = {1792-1082}, abstract = {The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.}, } @article {pmid37558640, year = {2023}, author = {Doi, K and Fujii, T and Hanamoto, M and Takamura, K and Nakada, T and Sato, Y and Ogura, K}, title = {[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {69}, number = {7}, pages = {189-192}, doi = {10.14989/ActaUrolJap_69_7_189}, pmid = {37558640}, issn = {0018-1994}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Hematuria ; *Prostatic Neoplasms/drug therapy/genetics/pathology ; Disease Progression ; Mutation ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; BRCA2 Protein/genetics ; }, abstract = {A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.}, } @article {pmid37558528, year = {2023}, author = {Downes, MR and Liu, KN and Yu, Y and Lajkosz, K and Kroon, LJ and Hollemans, E and Fleshner, N and Finelli, A and van Leenders, GJLH and Iczkowski, KA and van der Kwast, TH}, title = {Addition of Cribriform and Intraductal Carcinoma Presence to Prostate Biopsy Reporting Strengthens Pretreatment Risk Stratification Using CAPRA and NCCN Tools.}, journal = {Clinical genitourinary cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clgc.2023.07.013}, pmid = {37558528}, issn = {1938-0682}, abstract = {BACKGROUND: Pretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cribriform pattern 4 (CC).

OBJECTIVE: To assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts.

Matched prostate biopsies and radical prostatectomies from institutions in Toronto, Wisconsin and Rotterdam. The presence/absence of CC/IDC was recorded on all biopsies.

Relationship to outcome was assessed using Cox proportional hazard models, ANOVA and Harrell's concordance index.

RESULTS AND LIMITATIONS: We included 1326 patients (Toronto- 612, Wisconsin- 542, Rotterdam- 172) with median follow up of 4.2 years (IQR 2.9-6.4 years); 306 (23.1%) had CC/IDC on biopsy with 207 (20.9%) BCR and 154 (11.6%) events (metastases/death). Addition of CC/IDC improved stratification in CAPRA scores 3 to 5 for BCR-FS (c-index increase 0.633-0.658, P < .001) and scores 6-10 for EFS (c-index increase 0.653-0.697, P < .001). For NCCN, all risk groups apart from score 1 to 2 showed improvement in BCR-FS (c-index increase 0.599-0.636, P < 0.001) and EFS prediction (c-index increase 0.648-0.697, P < .001). Sub-analysis of grade group (GG) 2 biopsies showed similar findings. The retrospective nature and inclusion of cases only reported by genitourinary pathologists are study limitations.

CONCLUSIONS: The clinical benefit of the addition of CC/IDC to both CAPRA and NCCN pretreatment tools was validated in 3 cohorts, including the subset of biopsy GG2 prostate cancer patients.

PATIENT SUMMARY: Including additional pathologic features to existing pretreatment, clinical decision making tools improves the ability to predict prostate cancer recurrence, cancer spread and death of disease.}, } @article {pmid37555360, year = {2023}, author = {Chen, H and Li, X and Li, F and Li, Y and Chen, F and Zhang, L and Ye, F and Gong, M and Bu, H}, title = {Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.}, journal = {The Journal of pathology}, volume = {261}, number = {2}, pages = {125-138}, doi = {10.1002/path.6154}, pmid = {37555360}, issn = {1096-9896}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/metabolism ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Antioxidants ; Mass Spectrometry ; *Breast Neoplasms/diagnostic imaging ; }, abstract = {Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.}, } @article {pmid37552151, year = {2023}, author = {He, Y and Cazoulat, G and Wu, C and Svensson, S and Almodovar-Abreu, L and Rigaud, B and McCollum, E and Peterson, C and Wooten, Z and Rhee, DJ and Balter, P and Pollard-Larkin, J and Cardenas, C and Court, L and Liao, Z and Mohan, R and Brock, K}, title = {Quantifying the Effect of 4-Dimensional Computed Tomography-Based Deformable Dose Accumulation on Representing Radiation Damage for Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Standard-Fractionated Intensity-Modulated Radiation Therapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijrobp.2023.07.016}, pmid = {37552151}, issn = {1879-355X}, abstract = {PURPOSE: The aim of this study was to investigate the dosimetric and clinical effects of 4-dimensional computed tomography (4DCT)-based longitudinal dose accumulation in patients with locally advanced non-small cell lung cancer treated with standard-fractionated intensity-modulated radiation therapy (IMRT).

METHODS AND MATERIALS: Sixty-seven patients were retrospectively selected from a randomized clinical trial. Their original IMRT plan, planning and verification 4DCTs, and ∼4-month posttreatment follow-up CTs were imported into a commercial treatment planning system. Two deformable image registration algorithms were implemented for dose accumulation, and their accuracies were assessed. The planned and accumulated doses computed using average-intensity images or phase images were compared. At the organ level, mean lung dose and normal-tissue complication probability (NTCP) for grade ≥2 radiation pneumonitis were compared. At the region level, mean dose in lung subsections and the volumetric overlap between isodose intervals were compared. At the voxel level, the accuracy in estimating the delivered dose was compared by evaluating the fit of a dose versus radiographic image density change (IDC) model. The dose-IDC model fit was also compared for subcohorts based on the magnitude of NTCP difference (|ΔNTCP|) between planned and accumulated doses.

RESULTS: Deformable image registration accuracy was quantified, and the uncertainty was considered for the voxel-level analysis. Compared with planned doses, accumulated doses on average resulted in <1-Gy lung dose increase and <2% NTCP increase (up to 8.2 Gy and 18.8% for a patient, respectively). Volumetric overlap of isodose intervals between the planned and accumulated dose distributions ranged from 0.01 to 0.93. Voxel-level dose-IDC models demonstrated a fit improvement from planned dose to accumulated dose (pseudo-R[2] increased 0.0023) and a further improvement for patients with ≥2% |ΔNTCP| versus for patients with <2% |ΔNTCP|.

CONCLUSIONS: With a relatively large cohort, robust image registrations, multilevel metric comparisons, and radiographic image-based evidence, we demonstrated that dose accumulation more accurately represents the delivered dose and can be especially beneficial for patients with greater longitudinal response.}, } @article {pmid37548682, year = {2023}, author = {Mooshage, CM and Schimpfle, L and Kender, Z and Tsilingiris, D and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.}, journal = {Clinical neuroradiology}, volume = {}, number = {}, pages = {}, pmid = {37548682}, issn = {1869-1447}, abstract = {INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.

METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).

RESULTS: The K[trans] (HC 0.031 min[-1] ± 0.009, T2D 0.043 min[-1] ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with K[trans] (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively.

DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.}, } @article {pmid37546823, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, Autophagy, and YB-1 independent manner.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37546823}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3 % without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, } @article {pmid37540475, year = {2023}, author = {Shoshani, A and Kor, A}, title = {The longitudinal impact of the COVID-19 pandemic on adolescents' internalizing symptoms, substance use, and digital media use.}, journal = {European child & adolescent psychiatry}, volume = {}, number = {}, pages = {}, pmid = {37540475}, issn = {1435-165X}, abstract = {The present study examined the long-term effects of the COVID-19 pandemic on adolescent internalizing symptoms, substance use, and digital media use before and during the pandemic. A nationally representative longitudinal cohort of 3718 Israeli adolescents aged 12-16 at baseline completed measures of internalizing symptoms (anxiety, depression, and somatization), the prevalence of substance use (i.e., previous 30-day use of tobacco, alcohol, and cannabis), and average daily use of internet/television, video games, and social media. Social support and daily routines were assessed as potential protective factors for mental health. Data were collected in 10 public schools at four measurement points: before the Covid-19 outbreak (September 2019), after the first wave lockdown (May 2020), after the third wave lockdown (May 2021), and after the fifth wave of the pandemic (May 2022). Multi-level mixed models were used to analyze the longitudinal data. The results showed significant increases in internalizing symptoms, substance use (tobacco, alcohol, and cannabis), and daily screen time from the start of the study to the 33-month follow-up. Social support and daily routines moderated the increases in internalizing symptoms and digital media use. These findings highlight the need for public and educational mental health services to address the continuing impact of the pandemic on adolescents.}, } @article {pmid37536436, year = {2023}, author = {Abdollahi, E and Mozdarani, H}, title = {Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.}, journal = {Experimental and molecular pathology}, volume = {132-133}, number = {}, pages = {104865}, doi = {10.1016/j.yexmp.2023.104865}, pmid = {37536436}, issn = {1096-0945}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics/radiotherapy ; Epigenesis, Genetic ; Leukocytes, Mononuclear ; Radiation Tolerance/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; Protein Serine-Threonine Kinases ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.}, } @article {pmid37530887, year = {2023}, author = {Kishore, A and Venkataramana, L and Prasad, DVV and Mohan, A and Jha, B}, title = {Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.}, journal = {Medical & biological engineering & computing}, volume = {}, number = {}, pages = {}, pmid = {37530887}, issn = {1741-0444}, abstract = {Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.}, } @article {pmid37530324, year = {2023}, author = {Cakir, Y and Talu, CK and Trabulus, DC and Mermut, O}, title = {The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.}, journal = {Indian journal of pathology & microbiology}, volume = {66}, number = {3}, pages = {456-464}, doi = {10.4103/ijpm.ijpm_284_21}, pmid = {37530324}, issn = {0974-5130}, abstract = {BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.

AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.

MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.

STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.

RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.

CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.}, } @article {pmid37526280, year = {2023}, author = {Dao, E and Gohla, G and Williams, P and Lovrics, P and Badr, F and Fang, Q and Farrell, T and Farquharson, M}, title = {Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.}, journal = {Lasers in surgery and medicine}, volume = {55}, number = {8}, pages = {769-783}, doi = {10.1002/lsm.23710}, pmid = {37526280}, issn = {1096-9101}, mesh = {Humans ; Female ; Flavin-Adenine Dinucleotide ; NAD ; Breast/pathology ; *Neoplasms/pathology ; Spectrometry, Fluorescence ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; }, abstract = {OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated.

METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue.

RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification.

CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.}, } @article {pmid37524533, year = {2023}, author = {Neth, BJ and Raghunathan, A and Kizilbash, SH and Uhm, JH and Breen, WG and Johnson, DR and Daniels, DJ and Sener, U and Carabenciov, ID and Campian, JL and Khatua, S and Mahajan, A and Ruff, MW}, title = {Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.}, journal = {Neurology}, volume = {101}, number = {12}, pages = {e1256-e1271}, pmid = {37524533}, issn = {1526-632X}, mesh = {Child ; Humans ; Adult ; Male ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Female ; *Medulloblastoma/therapy/diagnosis ; Retrospective Studies ; *Cerebellar Neoplasms/therapy/diagnosis ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND AND OBJECTIVES: Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood.

METHODS: We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses.

RESULTS: We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses.

DISCUSSION: We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).}, } @article {pmid37521588, year = {2023}, author = {Shah, MH and Batool, M}, title = {Surviving the Test of Time: A Young Patient's Triumph Over Early-Onset Invasive Ductal Carcinoma and Its Recurrence a Decade Later.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42613}, pmid = {37521588}, issn = {2168-8184}, abstract = {Breast cancer is a complex, heterogeneous disease with diverse clinical presentations and variable outcomes. In this report, we provide a detailed analysis of a case involving a 22-year-old woman diagnosed with invasive ductal carcinoma, highlighting the difficulties of managing breast cancer in young patients. Through the examination of this patient's 10-year journey, from the initial diagnosis to surgery, adjuvant therapy, and recurrence, we underline the crucial role of early detection, personalised treatment, and interdisciplinary cooperation in optimising patient outcomes. Overall, the case study serves as a compelling narrative, effectively highlighting the aggressive nature of breast cancer in younger individuals and underscoring the need to provide care that addresses the multifaceted dimensions of this disease.}, } @article {pmid37520394, year = {2023}, author = {McFarland, BJ and Luo, A and Wang, X}, title = {Male breast cancer: Report of two cases with bloody nipple discharge.}, journal = {Radiology case reports}, volume = {18}, number = {9}, pages = {3323-3330}, pmid = {37520394}, issn = {1930-0433}, abstract = {We report 2 rare cases of male breast cancer with bloody nipple discharge. Patient 1, a 32-year-old male, presented with a bloody nipple discharge from the left breast. Diagnostic workup revealed papillary ductal carcinoma in situ. Patient 1 underwent bilateral mastectomy with left axillary sentinel lymph node biopsy and has been doing well ever since. Patient 2, a 70-year-old male with concomitant metastatic prostate cancer, presented with a palpable right breast mass and with initially serous, then bloody nipple discharge. Diagnostic workup revealed invasive ductal carcinoma with ductal carcinoma in situ of the right breast. Patient 2 received aromatase inhibitor therapy prior to right total mastectomy with SLN biopsy followed by adjuvant tamoxifen therapy. Patient 2 recovered without complication for 2 years until metastatic disease recurrence was detected. This case report's purpose is to increase awareness and enhance understanding of the presentation, diagnosis, treatment, and outcomes of rare malignant pathologies.}, } @article {pmid37519599, year = {2023}, author = {Grewal, IS and Rajagopal, T}, title = {Studying the Presentation of Paget Disease of the Breast.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e41057}, pmid = {37519599}, issn = {2168-8184}, abstract = {Paget disease of the breast is a rare breast cancer that accounts for 1-3% of all new presentations of breast cancer. It is characterized by an eczematous and ulcerative lesion of the nipple that may extend to the areola. Nearly 90% of cases are associated with underlying breast cancer. We report the presentation of Paget disease of the breast in a 41-year-old female, who presented due to a one-year history of an eczematous lesion of the left nipple area with no palpable mass, who was later found to have high-grade invasive ductal carcinoma treated with unilateral mastectomy and sentinel node biopsy.}, } @article {pmid37517027, year = {2023}, author = {Amato, S and Ramsey, J and Ahern, TP and Rovnak, J and Barlow, J and Weaver, D and Eyasu, L and Singh, R and Cintolo-Gonzalez, J}, title = {Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.}, journal = {Breast cancer research and treatment}, volume = {202}, number = {2}, pages = {325-334}, pmid = {37517027}, issn = {1573-7217}, mesh = {Cattle ; Humans ; Female ; Animals ; Sheep/genetics ; Male ; *Breast Neoplasms/epidemiology/genetics ; *Leukemia Virus, Bovine/genetics ; DNA, Viral/genetics ; Breast ; *Mammary Neoplasms, Animal ; }, abstract = {PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.

METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.

RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.

CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.}, } @article {pmid37513591, year = {2023}, author = {Hardt, LM and Herrmann, HJ and Reljic, D and Jaensch, P and Zerth, J and Neurath, MF and Zopf, Y}, title = {Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.}, journal = {Nutrients}, volume = {15}, number = {14}, pages = {}, pmid = {37513591}, issn = {2072-6643}, support = {MED1710//Hector-Stiftung/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; }, mesh = {Humans ; Quality of Life ; Nutritional Support ; *Malnutrition/diagnosis ; *Neoplasms/complications/therapy ; Exercise Therapy ; }, abstract = {Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.}, } @article {pmid37512689, year = {2023}, author = {Harnsoongnoen, S and Buranrat, B}, title = {Microwave Sensor for the Determination of DMSO Concentration in Water-DMSO Binary Mixture.}, journal = {Micromachines}, volume = {14}, number = {7}, pages = {}, pmid = {37512689}, issn = {2072-666X}, support = {//This research project was financially supported by Thailand Science Research and Innovation (TSRI)./ ; }, abstract = {This research aims to develop a microwave sensor to accurately measure the concentration of dimethyl sulfoxide (DMSO) in water-DMSO binary mixtures. The proposed sensor will utilize microwave frequency measurements to determine the DMSO concentration, providing a non-invasive and efficient method for analyzing DMSO solutions. The research will involve the design, fabrication, and testing of the sensor, as well as the development of an appropriate calibration model. The outcomes of this study will contribute to improved monitoring and quality control in various fields, including pharmaceuticals, chemical synthesis, and biomedical research. The binary mixtures of dimethyl sulfoxide (DMSO) and water with varying concentrations were investigated in the frequency range of 1 GHz to 5 GHz at room temperature using a microwave sensor. The proposed microwave sensor design was based on an interdigital capacitor (IDC) microstrip antenna loaded with a hexagonal complementary ring resonator (HCRR). The performance of the sensor, fabricated using the print circuit board (PCB) technique, was validated through simulations and experiments. The reflection coefficient (S11) and resonance frequency (Fr) of binary mixtures of DMSO and water solutions were recorded and analyzed for DMSO concentrations ranging from 0% v/v to 75% v/v. Mathematical models were developed to analyze the data, and laboratory tests showed that the sensor can detect levels of DMSO/water binary mixtures. The sensor is capable of detecting DMSO concentrations ranging from 0% v/v to 75% v/v, with a maximum sensitivity of 0.138 dB/% for S11 and ΔS11 and 0.2 MHz/% for Fr and ΔFr at a concentration of 50% v/v. The developed microwave sensor can serve as an alternative for detecting DMSO concentrations in water using a simple and cost-effective technique. This method can effectively analyze a wide range of concentrations, including highly concentrated solutions, quickly and easily.}, } @article {pmid37511674, year = {2023}, author = {Faraz, K and Dauce, G and Bouhamama, A and Leporq, B and Sasaki, H and Bito, Y and Beuf, O and Pilleul, F}, title = {Characterization of Breast Tumors from MR Images Using Radiomics and Machine Learning Approaches.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511674}, issn = {2075-4426}, support = {Not able to provide at the moment//FUJIFILM Healthcare Corporation/ ; }, abstract = {Determining histological subtypes, such as invasive ductal and invasive lobular carcinomas (IDCs and ILCs) and immunohistochemical markers, such as estrogen response (ER), progesterone response (PR), and the HER2 protein status is important in planning breast cancer treatment. MRI-based radiomic analysis is emerging as a non-invasive substitute for biopsy to determine these signatures. We explore the effectiveness of radiomics-based and CNN (convolutional neural network)-based classification models to this end. T1-weighted dynamic contrast-enhanced, contrast-subtracted T1, and T2-weighted MR images of 429 breast cancer tumors from 323 patients are used. Various combinations of input data and classification schemes are applied for ER[+] vs. ER[-], PR[+] vs. PR[-], HER2[+] vs. HER2[-], and IDC vs. ILC classification tasks. The best results were obtained for the ER[+] vs. ER[-] and IDC vs. ILC classification tasks, with their respective AUCs reaching 0.78 and 0.73 on test data. The results with multi-contrast input data were generally better than the mono-contrast alone. The radiomics and CNN-based approaches generally exhibited comparable results. ER and IDC/ILC classification results were promising. PR and HER2 classifications need further investigation through a larger dataset. Better results by using multi-contrast data might indicate that multi-parametric quantitative MRI could be used to achieve more reliable classifiers.}, } @article {pmid37503233, year = {2023}, author = {Rothschild, HT and Clelland, EN and Abel, MK and Chien, AJ and Shui, AM and Esserman, L and Khan, SA and Mukhtar, RA}, title = {The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37503233}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; }, abstract = {Purpose Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. Methods The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. Results In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. Conclusion Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.}, } @article {pmid37500355, year = {2023}, author = {Ding, W and Ye, D and Zhu, H and Lin, Y and Li, Z and Ruan, G}, title = {Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.}, journal = {Clinical breast cancer}, volume = {23}, number = {7}, pages = {e441-e450}, doi = {10.1016/j.clbc.2023.07.004}, pmid = {37500355}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Retrospective Studies ; Biomarkers, Tumor ; Prognosis ; Chemotherapy, Adjuvant ; Proportional Hazards Models ; Neoplasm Recurrence, Local/pathology ; }, abstract = {INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.

METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.

RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).

CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.}, } @article {pmid37500131, year = {2023}, author = {Namikawa, T and Yokota, K and Maeda, H and Kitagawa, H and Tamura, M and Satake, H and Sugimoto, T and Kobayashi, M and Hanazaki, K and Seo, S}, title = {Gastric and Bone Metastases Arising from Invasive Lobular Carcinoma With Ductal Carcinoma Occurring in one Breast Synchronously.}, journal = {Anticancer research}, volume = {43}, number = {8}, pages = {3701-3707}, doi = {10.21873/anticanres.16553}, pmid = {37500131}, issn = {1791-7530}, mesh = {Female ; Humans ; Aged ; *Carcinoma, Lobular/pathology ; Fluorodeoxyglucose F18 ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Bone Neoplasms ; Stomach/pathology ; }, abstract = {BACKGROUND/AIM: We report the case of a patient with gastric and bone metastases arising from an invasive lobular carcinoma of the breast coexisting with ductal carcinoma at the same time.

CASE REPORT: A 68-year-old woman with gastric and right costal tumors was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed irregular, slightly elevated lesions extending from the gastric body to the antrum, and biopsy specimens revealed a poorly differentiated adenocarcinoma. Furthermore, abdominal contrast-enhanced computed tomography (CT) revealed extensive wall thickening with homogeneous enhancement in the stomach. 18F-2-deoxy-2-fluoro-glucose positron emission tomography (FDG-PET) showed intense FDG uptake in the right mammary gland and right third rib. Moreover, fine-needle aspiration of the third right rib lump and the right breast mass lesion was performed, and subsequent pathological investigations revealed metastatic adenocarcinoma and invasive ductal carcinoma, respectively. Immunohistochemical examination revealed that estrogen receptor was strongly positive (>95%) in breast cancer and focally positive (<5%) in gastric cancer with bone metastasis. In addition, another right breast tumor was detected by breast magnetic resonance imaging (MRI), and biopsy revealed invasive lobular carcinoma that matched the histological findings of bone and gastric lesions, including immunohistochemical examination. The patient was treated with an aromatase inhibitor, a CDK4/6 inhibitor, and a receptor activator of nuclear factor-kappa B ligand (RANKL) monoclonal antibody. She showed no symptoms or disease progression at 9-month follow-up after the initiation of systemic drug treatment.

CONCLUSION: Invasive lobular carcinoma can metastasize to the gastrointestinal tract, and new treatment developments are expected as more cases will accumulate in the future.}, } @article {pmid37498719, year = {2023}, author = {Shoshani, A}, title = {Longitudinal changes in children's and adolescents' mental health and well-being and associated protective factors during the COVID-19 pandemic.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {}, number = {}, pages = {}, doi = {10.1037/tra0001556}, pmid = {37498719}, issn = {1942-969X}, abstract = {OBJECTIVE: The COVID-19 pandemic has heightened children's and adolescents' risk of experiencing long-term mental health problems and a decline in subjective well-being. To better understand the longitudinal impact of COVID-19, this study explored the role of demographic variables and the potential moderating effects of social support and daily routines as resilience factors.

METHOD: A nationally representative, longitudinal cohort of 5,217 Israeli children and adolescents aged 10-15 at baseline completed measures of mental health symptoms, life satisfaction, positive and negative emotions, gratitude, social support, and daily routines. Data were collected in school at four measurement points: September 2019 (before the outbreak of COVID-19; N = 5,127), May 2020 (after the first lockdown; N = 4,698), May 2021 (after the third wave lockdown; N = 4,813), and May 2022 (after the fourth and fifth waves of the pandemic; N = 4,897). The data were analyzed using multilevel mixed models.

RESULTS: Significant increases in depression, anxiety, and panic along with decreases in psychological well-being were found as a function of time. These effects were moderated by age and gender. Participants with high social support and structured daily routines reported smaller increases in mental health symptoms than students with low social support or irregular daily routines.

CONCLUSION: There is a critical need for clinical and educational interventions for young people during this period to promote the resilience factors that can moderate well-being and counter the decline in mental health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37496230, year = {2023}, author = {Konishi, K and Araya, J and Nagabuchi, M and Sakamoto, T and Ogino, J and Hirano, S}, title = {[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {7}, pages = {825-827}, pmid = {37496230}, issn = {0385-0684}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/surgery/pathology ; Docetaxel/therapeutic use ; Mastectomy ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Squamous Cell/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Cyclophosphamide/therapeutic use ; *Liver Neoplasms/drug therapy/surgery/secondary ; }, abstract = {Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.}, } @article {pmid37495452, year = {2023}, author = {Bódis, K and Bombrich, M and Schön, M and Knebel, B and Zaharia, OP and Bönhof, G and Karusheva, Y and Strassburger, K and Kupriyanova, Y and Kotzka, J and Guthoff, R and Schrauwen-Hinderling, V and Al-Hasani, H and Burkart, V and Szendroedi, J and Wagner, R and Markgraf, DF and Roden, M and , }, title = {Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {33}, number = {9}, pages = {1785-1796}, doi = {10.1016/j.numecd.2023.06.004}, pmid = {37495452}, issn = {1590-3729}, mesh = {Humans ; Male ; Case-Control Studies ; *Diabetes Mellitus, Type 2/diagnosis/genetics/complications ; *Insulin Resistance/genetics ; Liver/metabolism ; *Liver Neoplasms ; Membrane Proteins/genetics/metabolism ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics/complications ; Polymorphism, Single Nucleotide ; Triglycerides/metabolism ; }, abstract = {BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.

METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n = 16) or without (TM6SF2[EE]: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.

CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.}, } @article {pmid37493324, year = {2023}, author = {Lee, SE and Yoon, JH and Son, NH and Han, K and Moon, HJ}, title = {Screening in Patients With Dense Breasts: Comparison of Mammography, Artificial Intelligence, and Supplementary Ultrasound.}, journal = {AJR. American journal of roentgenology}, volume = {}, number = {}, pages = {}, doi = {10.2214/AJR.23.29655}, pmid = {37493324}, issn = {1546-3141}, abstract = {Background: Screening mammography has decreased performance in patients with dense breasts. Supplementary screening ultrasound is a recommended option in such patients, although has yielded mixed results in prior investigation. Objective: To compare the performance characteristics of screening mammography alone, standalone artificial intelligence (AI), ultrasound alone, as well as mammography in combination with AI and/or ultrasound, in patients with dense breasts. Methods: This retrospective study included 1325 women (mean age, 53 years) with dense breasts who underwent both screening mammography and supplementary breast ultrasound within a 1-month interval from January 2017 to December 2017; prior mammogram and prior ultrasound were available for comparison in 91.2% and 91.8%, respectively. Mammography and ultrasound examinations were interpreted by one of 15 radiologists (5 staff; 10 fellows); clinical reports were used for the present analysis. A commercial AI tool was used to retrospectively evaluate mammographic examinations for presence of cancer. Screening performances were compared among mammography, AI, ultrasound, and test combinations, using generalized estimating equations. Benign diagnoses required ≥24 months of imaging stability. Results: Twelve cancers (6 invasive ductal carcinoma; 6 ductal carcinoma in situ) were diagnosed. Mammography, standalone AI, and ultrasound showed cancer detection rate (per 1000 patients) of 6.0, 6.8, and 6.0 (all p>.05); recall rate of 4.4%, 11.9%, and 9.2% (all p<.05); sensitivity of 96.2%, 88.7%, and 91.3% (all p>.05); specificity of 96.2%, 88.7%, and 91.3% (all p>.50); and accuracy of 95.9%, 88.5%, and 91.1% (all p<.05). Mammography with AI, mammography with ultrasound, and mammography with both ultrasound and AI showed CDR of 7.5, 9.1, and 9.1 (all p>.05); recall rate of 14.9, 11.7, and 21.4 (all p<.05); sensitivity of 83.3%, 100.0%, and 100.0% (all p>.05); specificity of 85.8%, 89.1%, and 79.4% (all p<.05); and accuracy of 85.7%, 89.2%, and 79.5% (all p<.05). Conclusion: Mammography with supplementary ultrasound showed higher accuracy, higher specificity, and lower recall rate in comparison to mammography with AI as well as in comparison to mammography with both ultrasound and AI. Clinical Impact: The findings fail to show benefit of AI with respect to screening mammography performed with supplementary breast ultrasound in patients with dense breasts.}, } @article {pmid37492824, year = {2023}, author = {Kalantri, P and Lomashvili, K}, title = {Deruxtecan-Induced Reversible Fanconi Syndrome.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40890}, pmid = {37492824}, issn = {2168-8184}, abstract = {Increasingly complex and constantly emerging cancer treatment protocols are associated with kidney toxicities. Data clearly demonstrate that when patients with cancer develop acute or chronic kidney disease, severe fluid and electrolyte abnormalities, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. We present a case of a 74-year-old woman with metastatic, recurrent ER+/PR-/HER2+ invasive ductal carcinoma of the right breast, status post bilateral mastectomies, chemotherapy, radiation therapy, and hormonal therapies, who were clinically stable on Trastuzumab/Pertuzumab maintenance for about a year. She then experienced disease progression. She was started on Trastuzumab+Deruxtecan (T-Dxt). However, due to worsening diarrhea of more than 12 episodes per day, decreased oral intake, weakness and weight loss, she got admitted to the hospital. Laboratory data showed hyponatremia, hypokalemia, non-anion gap metabolic acidosis, hypomagnesemia, and hypophosphatemia. These laboratory abnormalities were initially attributed to diarrhea. Renal losses were suspected when the electrolyte abnormalities did not correct despite improving diarrhea. Urine electrolytes were hence tested. There was evidence of Fanconi syndrome with glucosuria, proteinuria, and renal potassium and phosphorus wasting. Fanconi syndrome was attributed to the Deruxtecan component of the combination chemotherapy, as she was previously on Trastuzumab with no such abnormalities. The electrolyte abnormalities resolved over the course of a few months. To our knowledge, this is the first case of Fanconi syndrome due to T-Dxt.}, } @article {pmid37492470, year = {2023}, author = {Li, Y and Zhang, Y and Zhou, Z and Shang, L and Huang, Y and Lu, X and Cheng, S}, title = {Predictive value of controlling nutritional status score in postoperative recurrence and metastasis of breast cancer patients with HER2-low expression.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1116631}, pmid = {37492470}, issn = {2234-943X}, abstract = {BACKGROUND: To investigate the predictive value of controlling nutritional status (CONUT) score in Postoperative Recurrence and Metastasis of Breast Cancer Patients with HER2-Low Expression.

METHODS: The clinicopathological data of 697 female breast cancer patients who pathology confirmed invasive ductal carcinoma and surgery in Harbin Medical University Tumor Hospital from January 2014 to January 2017 were retrospectively analyzed. The relationship between CONUT score and various clinicopathological factors as well as prognosis was evaluated.

RESULTS: Based on the cut-off point of ROC curve, compared with the low CONUT score group, the high CONUT score group had worse 5-year RFS. In subgroup analysis, compared with the low CONUT group, the high CONUT group had worse prognosis at different TNM stages. Univariate and multivariate results showed that the low CONUT score group had better overall survival and recurrence-free survival than the high CONUT group.

CONCLUSION: CONUT score is an independent predictor of postoperative recurrence and metastasis in HER2-low breast cancer patients. It is may be used as an effective tool to predict the recurrence and metastasis of HER2-low breast cancer.}, } @article {pmid37490163, year = {2023}, author = {Goldhaber, NH and O'Keefe, T and Kang, J and Douglas, S and Blair, SL}, title = {Is Choosing Wisely Wise for Lobular Carcinoma in Patients Over 70 Years of Age? A National Cancer Database Analysis of Sentinel Node Practice Patterns.}, journal = {Annals of surgical oncology}, volume = {30}, number = {10}, pages = {6024-6032}, pmid = {37490163}, issn = {1534-4681}, mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; *Carcinoma, Lobular/surgery/pathology ; *Carcinoma, Ductal, Breast/surgery/pathology ; Neoplasm Staging ; *Breast Neoplasms/surgery/pathology ; *Sentinel Lymph Node/surgery/pathology ; *Lymphadenopathy ; }, abstract = {BACKGROUND: Controversy continues in the treatment of breast cancer in women over 70 years of age. In 2016, the Society of Surgical Oncology recommended against routine use of sentinel lymph node biopsy (SLNBx) as part of the 'Choosing Wisely Campaign'. This study examines the oncologic safety of avoidance of routine SLNBx in patients over 70 years of age with invasive lobular carcinoma (ILC).

METHODS: The National Cancer Database was used to identify women with invasive ductal carcinoma (IDC) and ILC diagnosed between 2012 and 2020. Clinical and pathological staging, axillary staging, surgery type, and lymph node positivity between patients with IDC or ILC were compared.

RESULTS: Among women with T1 tumors, 85,949 (79.6%) patients with IDC and 12,761 (81.5%) patients with ILC underwent SLNBx (p < 0.001). Among patients who underwent SLNBx, those with IDC were more likely to have positive nodes (n = 7535, 8.8%) than those with ILC (n = 1041, 8.2%; p = 0.02). During the time interval of interest, for both IDC and ILC patients, the rate of axillary lymph node dissection decreased and rates of SLNBx or no axillary staging increased. On multivariate analysis, ILC histology was associated with use of SLNBx, but without nodal positivity.

CONCLUSION: A trend de-escalation of axillary staging was identified in this study, however the majority of patients meeting the 'Choosing Wisely' criteria are still undergoing SLNBx. No increased risk of nodal positivity was identified among patients with ILC, suggesting that surgeons can continue to choose wisely and limit the use of SLNBx in women over 70 years of age with T1 ILC tumors.}, } @article {pmid37490055, year = {2023}, author = {Choo, ZY and Xu, AZ}, title = {Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.}, journal = {Archives of dermatological research}, volume = {315}, number = {9}, pages = {2725-2728}, pmid = {37490055}, issn = {1432-069X}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/therapy ; Skin/pathology ; Administration, Cutaneous ; *Carcinoma, Lobular/pathology/secondary ; }, } @article {pmid37489961, year = {2023}, author = {Sanchez, D and Bloomquist, E and Wright, H and Barnavon, Y}, title = {Immediate Nipple Reconstruction With Areolar Flaps After Nipple Excision.}, journal = {Annals of plastic surgery}, volume = {91}, number = {2}, pages = {211-214}, doi = {10.1097/SAP.0000000000003570}, pmid = {37489961}, issn = {1536-3708}, mesh = {Humans ; Female ; Nipples ; *Carcinoma, Intraductal, Noninfiltrating ; *Breast Neoplasms ; Esthetics ; Genetic Predisposition to Disease ; }, abstract = {Nipple-sparing mastectomies (NSMs) have become a common surgical approach in the management of invasive breast cancers and ductal carcinoma in situ, and as a risk-reducing approach in genetically predisposed patients. The current standard of care in the management of positive nipple margin after NSM is total excision of the nipple-areola complex. In this article, we aimed to present a case series describing a novel approach to positive nipple margins with nipple-only excision and immediate nipple reconstruction using areolar flaps in patients who underwent NSM for noninvasive tumors. We conducted a retrospective review of patients who underwent NSM and were found to have positive nipple margins and underwent subsequent nipple excision with immediate areolar flap reconstruction. We identified 6 patients who underwent NSM and were found to have nipple margins-5 for ductal carcinoma in situ and 1 for invasive ductal carcinoma. These patients underwent nipple excision with immediate reconstruction using "sickle" flaps. We concluded that if nipple excision and immediate reconstruction with areolar sickle flaps can be performed, it results in good aesthetic outcomes without compromising oncologic results.}, } @article {pmid37480503, year = {2023}, author = {D'Iorio, A and Aiello, EN and Amboni, M and Vitale, C and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G}, title = {Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {10}, pages = {2157-2163}, pmid = {37480503}, issn = {1720-8319}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis ; Retrospective Studies ; Mental Status and Dementia Tests ; *Cognitive Dysfunction/diagnosis/etiology ; Language ; }, abstract = {BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.

METHODS: A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.

RESULTS: The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).

DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.}, } @article {pmid37480256, year = {2023}, author = {White, D and Sadough Shahmirzadi, M and Boulmay, B}, title = {Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.}, journal = {Journal of investigative medicine high impact case reports}, volume = {11}, number = {}, pages = {23247096231188251}, pmid = {37480256}, issn = {2324-7096}, abstract = {Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.}, } @article {pmid37479943, year = {2023}, author = {Adachi, Y and Asaga, S and Kumamaru, H and Kinugawa, N and Sagara, Y and Niikura, N and Jinno, H and Saji, S and Toi, M}, title = {Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {397-408}, pmid = {37479943}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/therapy ; *Carcinoma, Lobular/therapy ; East Asian People ; Prognosis ; Registries ; }, abstract = {PURPOSE: Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC.

METHODS: We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups.

RESULTS: For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases.

CONCLUSION: Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.}, } @article {pmid37479756, year = {2023}, author = {Tian, Z and Yang, Z and Jin, M and Ding, R and Wang, Y and Chai, Y and Wu, J and Yang, M and Zhao, W}, title = {Identification of cytokine-predominant immunosuppressive class and prognostic risk signatures in glioma.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37479756}, issn = {1432-1335}, support = {JJKH20181256KJ//The Scientific Research Planning Project of the Education Department of Jilin Province/ ; }, abstract = {PURPOSE: The advent of immune checkpoint blockade (ICB) therapies this year has changed the way glioblastoma (GBM) is treated. Meanwhile, some patients with strong PD-L1 expression remain immune checkpoint resistant. To better understand the molecular processes that influence the immune environment, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to predict patient survival outcomes.

PATIENTS AND METHODS: Our study analyzed RNA-sequencing data from 178 GBM samples. Their unique gene expression patterns in the tumor microenvironment were analyzed by an unsupervised clustering algorithm. Through these expression patterns, a panel of T-cell exhaustion signatures, immunosuppressive cells, and clinical features correlates with immunotherapy response. The presence or absence of immune status and prognostic signatures was then validated with the test dataset.

RESULTS: 38.2% of GBM patients showed increased expression of anti-inflammatory cytokines, significant enrichment of T cell exhaustion signals, higher proportion of immunosuppressive cells (macrophages and CD4 regulatory T cells) and nine inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA). The immunodepleted class (IDC) was used to classify these immunocompromised individuals. Despite the high density of tumor-infiltrating lymphocytes shown by IDC, such patients have a poor prognosis. Although PD-L1 was highly expressed in IDC, it suggested that there might be ICB resistance. There are many IDC predictive signatures to discover.

CONCLUSION: PD-1 is strongly expressed in a novel immunosuppressive class of GBM, but this cluster may be resistant to ICB therapy. A comprehensive description of this drug-resistant tumor microenvironment could provide new insights into drug resistance mechanisms and improved immunotherapy techniques.}, } @article {pmid37478120, year = {2023}, author = {Shi, K and Liu, XL and Guo, Q and Zhang, YQ and Fan, ST and Dai, L and Jiang, N and Li, D}, title = {TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0285817}, pmid = {37478120}, issn = {1932-6203}, mesh = {Female ; Humans ; *Endometrial Neoplasms/pathology ; Prognosis ; Nomograms ; RNA ; Biomarkers, Tumor/genetics/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.

METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.

RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.

CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.}, } @article {pmid37478042, year = {2023}, author = {Zhang, W and Yang, L and Geng, S and Hong, S}, title = {Self-Supervised Time Series Representation Learning via Cross Reconstruction Transformer.}, journal = {IEEE transactions on neural networks and learning systems}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TNNLS.2023.3292066}, pmid = {37478042}, issn = {2162-2388}, abstract = {Since labeled samples are typically scarce in real-world scenarios, self-supervised representation learning in time series is critical. Existing approaches mainly employ the contrastive learning framework, which automatically learns to understand similar and dissimilar data pairs. However, they are constrained by the request for cumbersome sampling policies and prior knowledge of constructing pairs. Also, few works have focused on effectively modeling temporal-spectral correlations to improve the capacity of representations. In this article, we propose the cross reconstruction transformer (CRT) to solve the aforementioned issues. CRT achieves time series representation learning through a cross-domain dropping-reconstruction task. Specifically, we obtain the frequency domain of the time series via the fast Fourier transform (FFT) and randomly drop certain patches in both time and frequency domains. Dropping is employed to maximally preserve the global context while masking leads to the distribution shift. Then a Transformer architecture is utilized to adequately discover the cross-domain correlations between temporal and spectral information through reconstructing data in both domains, which is called Dropped Temporal-Spectral Modeling. To discriminate the representations in global latent space, we propose instance discrimination constraint (IDC) to reduce the mutual information between different time series samples and sharpen the decision boundaries. Additionally, a specified curriculum learning (CL) strategy is employed to improve the robustness during the pretraining phase, which progressively increases the dropping ratio in the training process. We conduct extensive experiments to evaluate the effectiveness of the proposed method on multiple real-world datasets. Results show that CRT consistently achieves the best performance over existing methods by 2%-9%. The code is publicly available at https://github.com/BobZwr/Cross-Reconstruction-Transformer.}, } @article {pmid37474400, year = {2023}, author = {Chappidi, MR and Sjöström, M and Greenland, NY and Cowan, JE and Baskin, AS and Shee, K and Simko, JP and Chan, E and Stohr, BA and Washington, SL and Nguyen, HG and Quigley, DA and Davicioni, E and Feng, FY and Carroll, PR and Cooperberg, MR}, title = {Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.}, journal = {European urology oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euo.2023.06.007}, pmid = {37474400}, issn = {2588-9311}, abstract = {BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.

OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.

This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.

Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.

RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.

CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.

PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.}, } @article {pmid37470893, year = {2023}, author = {Chen, BF and Tsai, YF and Lien, PJ and Lin, YS and Feng, CJ and Chen, YJ and Cheng, HF and Tseng, LM and Huang, CC}, title = {Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {547-560}, pmid = {37470893}, issn = {1573-7217}, support = {V110E-005-3//Taipei Veterans General Hospital/ ; V111E-006-3//Taipei Veterans General Hospital/ ; V112E-004-3//Taipei Veterans General Hospital/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/epidemiology/genetics/therapy ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Taiwan/epidemiology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; Treatment Outcome ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.

METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.

RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05).

CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.}, } @article {pmid37458802, year = {2023}, author = {de Araújo, RA and da Luz, FAC and da Costa Marinho, E and Nascimento, CP and Mendes, TR and Mosca, ERT and de Andrade Marques, L and Delfino, PFR and Antonioli, RM and da Silva, ACAL and Dos Reis Monteiro, MLG and Neto, MB and Silva, MJB}, title = {The elusive Luminal B breast cancer and the mysterious chemokines.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37458802}, issn = {1432-1335}, abstract = {PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients.

METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1β), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)].

RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r =  0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1β/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases.

CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.}, } @article {pmid37444563, year = {2023}, author = {Modena, D and Moras, ML and Sandrone, G and Stevenazzi, A and Vergani, B and Dasgupta, P and Kliever, A and Gulde, S and Marangelo, A and Schillmaier, M and Luque, RM and Bäuerle, S and Pellegata, NS and Schulz, S and Steinkühler, C}, title = {Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas.}, journal = {Cancers}, volume = {15}, number = {13}, pages = {}, pmid = {37444563}, issn = {2072-6694}, abstract = {Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.}, } @article {pmid37444482, year = {2023}, author = {Kang, MK and Jiang, F and Kim, YJ and Ryu, K and Masamune, A and Hamada, S and Park, YY and Koh, SS}, title = {CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).}, journal = {Cancers}, volume = {15}, number = {13}, pages = {}, pmid = {37444482}, issn = {2072-6694}, support = {No. 2018R1D1A3B05050725//Ministry of Education/ ; }, abstract = {[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.}, } @article {pmid37443686, year = {2023}, author = {Su, IL and Chen, YK}, title = {Utility of FDG PET/CT in Patient with Synchronous Breast and Colon Cancer.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {37443686}, issn = {2075-4418}, abstract = {The most common malignancy in women is breast cancer, and the second one is colon cancer. Synchronous breast and colon cancers are rare. Here, we reported a 60-year-old woman with a left breast mass for six months. Biopsy revealed an invasive ductal carcinoma. She underwent 2-[Fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan for evaluation of the extent of the disease. FDG PET/CT revealed an advanced left breast cancer with multiple metastases in both regional and distant lymph nodes (in left axilla level I/II, lower paratracheal region, and right lung hilum), bilateral lungs, and axial and proximal appendicular skeletons. An early staged synchronous colon cancer was detected incidentally on FDG PET/CT images. After endoscopic mucosal resection of colon cancer, she received palliative chemotherapy for breast cancer with a marked therapeutic response. The disease status of post-treated breast cancer remained relatively stationary for more than one year. Brain metastasis was noted afterward. Nevertheless, there was no evidence of colon cancer recurrence throughout her breast cancer disease course.}, } @article {pmid37442866, year = {2023}, author = {Yang, J and Hussein Kadir, D}, title = {Data mining techniques in breast cancer diagnosis at the cellular-molecular level.}, journal = {Journal of cancer research and clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {37442866}, issn = {1432-1335}, abstract = {INTRODUCTION: Studies in the field of better diagnosis of breast cancer using machine learning and data mining techniques have always been promising. A new diagnostic method can detect the characteristics of breast cancer in the early stages and help in better treatment. The aim of this study is to provide a method for early detection of breast cancer by reducing human errors based on data mining techniques in medicine using accurate and rapid screening.

METHODOLOGY: The proposed method includes data pre-processing and image quality improvement in the first step. The second step consists of separating cancer cells from healthy breast tissue and removing outliers using image segmentation. Finally, a classification model is configured by combining deep neural networks in the third phase. The proposed ensemble classification model uses several effective features extracted from images and is based on majority vote. This model can be used as a screening system to diagnose the grade of invasive ductal carcinoma of the breast.

RESULTS: Evaluations have been done using two histopathological microscopic datasets including patients with invasive ductal carcinoma of the breast. With extracting high-level features with average accuracies of 92.65% and 93.34% in these two datasets, the proposed method has succeeded in quickly diagnosing and classifying breast cancer with high performance.

CONCLUSION: By combining deep neural networks and extracting features affecting breast cancer, the ability to diagnose with the highest accuracy is provided, and this is a step toward helping specialists and increasing the chances of patients' survival.}, } @article {pmid37441009, year = {2023}, author = {Sasamoto, M and Yamada, A and Oshi, M and Ota, I and Yoshida, K and Yakeishi, M and Tsuura, Y and Masui, H and Endo, I}, title = {Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review.}, journal = {Gland surgery}, volume = {12}, number = {6}, pages = {853-859}, pmid = {37441009}, issn = {2227-684X}, abstract = {BACKGROUND: Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB).

CASE DESCRIPTION: A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery.

CONCLUSIONS: Invasive ductal carcinoma may spontaneously regress after preoperative CNB.}, } @article {pmid37439959, year = {2023}, author = {Tsunokake, S and Iwabuchi, E and Miki, Y and Kanai, A and Onodera, Y and Sasano, H and Ishida, T and Suzuki, T}, title = {SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {499-513}, pmid = {37439959}, issn = {1573-7217}, mesh = {Humans ; Female ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; *Breast Neoplasms/drug therapy/genetics ; Glucose/metabolism ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.

METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.

RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.

CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.}, } @article {pmid37436978, year = {2023}, author = {Conway, JRW and Dinç, DD and Follain, G and Paavolainen, O and Kaivola, J and Boström, P and Hartiala, P and Peuhu, E and Ivaska, J}, title = {IGFBP2 secretion by mammary adipocytes limits breast cancer invasion.}, journal = {Science advances}, volume = {9}, number = {28}, pages = {eadg1840}, pmid = {37436978}, issn = {2375-2548}, mesh = {Female ; Humans ; Adipocytes ; Antibodies, Neutralizing ; Breast ; *Breast Neoplasms ; Insulin-Like Growth Factor II ; }, abstract = {The progression of noninvasive ductal carcinoma in situ to invasive ductal carcinoma for patients with breast cancer results in a significantly poorer prognosis and is the precursor to metastatic disease. In this work, we have identified insulin-like growth factor-binding protein 2 (IGFBP2) as a potent adipocrine factor secreted by healthy breast adipocytes that acts as a barrier against invasive progression. In line with this role, adipocytes differentiated from patient-derived stromal cells were found to secrete IGFBP2, which significantly inhibited breast cancer invasion. This occurred through binding and sequestration of cancer-derived IGF-II. Moreover, depletion of IGF-II in invading cancer cells using small interfering RNAs or an IGF-II-neutralizing antibody ablated breast cancer invasion, highlighting the importance of IGF-II autocrine signaling for breast cancer invasive progression. Given the abundance of adipocytes in the healthy breast, this work exposes the important role they play in suppressing cancer progression and may help expound upon the link between increased mammary density and poorer prognosis.}, } @article {pmid37435234, year = {2023}, author = {Li, S and Tong, J and Li, H and Mao, C and Shen, W and Lei, Y and Hu, P}, title = {L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {4435-4442}, pmid = {37435234}, issn = {1178-6973}, abstract = {We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.}, } @article {pmid37428725, year = {2023}, author = {Cosar, R and Sut, N and Topaloglu, S and Tastekin, E and Nurlu, D and Ozler, T and Şenödeyici, E and Dedeli, M and Chousein, M and Cicin, I}, title = {Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0283445}, pmid = {37428725}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/therapy/pathology ; Mastectomy ; Treatment Outcome ; Prognosis ; *Breast Neoplasms, Male/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups.

PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test.

RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival.

CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.}, } @article {pmid37421735, year = {2023}, author = {Krishna Swaroop, A and Krishnan Namboori, PK and Esakkimuthukumar, M and Praveen, TK and Nagarjuna, P and Patnaik, SK and Selvaraj, J}, title = {Leveraging decagonal in-silico strategies for uncovering IL-6 inhibitors with precision.}, journal = {Computers in biology and medicine}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.compbiomed.2023.107231}, pmid = {37421735}, issn = {1879-0534}, mesh = {Humans ; Molecular Docking Simulation ; *Interleukin-6 Inhibitors ; *Methotrexate ; Interleukin-6 ; Molecular Dynamics Simulation ; Inflammation ; }, abstract = {Interleukin-6 upregulation leads to various acute phase reactions such as local inflammation and systemic inflammation in many diseases like cancer, multiple sclerosis, rheumatoid arthritis, anemia, and Alzheimer's disease stimulating JAK/STAT3, Ras/MAPK, PI3K-PKB/Akt pathogenic pathways. Since no small molecules are available in the market against IL-6 till now, we have designed a class of small bioactive 1,3 - indanedione (IDC) molecules for inhibiting IL-6 using a decagonal approach computational studies. The IL-6 mutations were mapped in the IL-6 protein (PDB ID: 1ALU) from thorough pharmacogenomic and proteomics studies. The protein-drug interaction networking analysis for 2637 FFDA-approved drugs with IL-6 protein using Cytoscape software showed that 14 drugs have prominent interactions with IL-6. Molecular docking studies showed that the designed compound IDC-24 (-11.8 kcal/mol) and methotrexate (-5.20) bound most strongly to the 1ALU south asian population mutated protein. MMGBSA results indicated that IDC-24 (-41.78 kcal/mol) and methotrexate (-36.81 kcal/mol) had the highest binding energy when compared to the standard molecules LMT-28 (-35.87 kcal/mol) and MDL-A (-26.18 kcal/mol). These results we substantiated by the molecular dynamic studies in which the compound IDC-24 and the methotrexate had the highest stability. Further, the MMPBSA computations produced energies of -28 kcal/mol and -14.69 kcal/mol for IDC-24 and LMT-28. KDeep absolute binding affinity computations revealed energies of -5.81 kcal/mol and -4.74 kcal/mol for IDC-24 and LMT-28 respectively. Finally, our decagonal approach established the compound IDC-24 from the designed 1,3-indanedione library and methotrexate from protein drug interaction networking as suitable HITs against IL-6.}, } @article {pmid37420729, year = {2023}, author = {Sharma, RK and Issac, B and Xin, Q and Gadekallu, TR and Nath, K}, title = {Plant and Salamander Inspired Network Attack Detection and Data Recovery Model.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, pmid = {37420729}, issn = {1424-8220}, mesh = {*Biological Evolution ; *Internet ; Machine Learning ; }, abstract = {The number of users of the Internet has been continuously rising, with an estimated 5.1 billion users in 2023, which comprises around 64.7% of the total world population. This indicates the rise of more connected devices to the network. On average, 30,000 websites are hacked daily, and nearly 64% of companies worldwide experience at least one type of cyberattack. As per IDC's 2022 Ransomware study, two-thirds of global organizations were hit by a ransomware attack that year. This creates the desire for a more robust and evolutionary attack detection and recovery model. One aspect of the study is the bio-inspiration models. This is because of the natural ability of living organisms to withstand various odd circumstances and overcome them with an optimization strategy. In contrast to the limitations of machine learning models with the need for quality datasets and computational availability, bio-inspired models can perform in low computational environments, and their performances are designed to evolve naturally with time. This study concentrates on exploring the evolutionary defence mechanism in plants and understanding how plants react to any known external attacks and how the response mechanism changes to unknown attacks. This study also explores how regenerative models, such as salamander limb regeneration, could build a network recovery system where services could be automatically activated after a network attack, and data could be recovered automatically by the network after a ransomware-like attack. The performance of the proposed model is compared to open-source IDS Snort and data recovery systems such as Burp and Casandra.}, } @article {pmid37409201, year = {2023}, author = {Khalid, S and Atiq, A and Khalid, F and Khan, FW and Bashir, A}, title = {Invasive Micropapillary Carcinoma of the Breast With Solid Papillary Carcinoma: A Case Report.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e39928}, pmid = {37409201}, issn = {2168-8184}, abstract = {Invasive micropapillary carcinoma and Solid papillary carcinomas are rare histologic subtypes of breast cancer. Co-existence of tumors of the breast like invasive ductal and lobular carcinomas, or invasive ductal carcinoma and mucinous carcinomas have been reported before. But the existence of invasive micropapillary carcinoma with solid papillary carcinoma is a rare occurrence. Here, we are reporting a rare case of a 60-year-old female with a mass in her left breast. The histopathology report showed a tumor containing these two histologic subtypes. Recognition of all tumor subtypes is necessary, as this can impact the treatment strategy.}, } @article {pmid37408681, year = {2023}, author = {Martinez, C and Meterissian, S and Saidi, A and Tremblay, F and Meguerditchian, AN and Fleiszer, D and Lambert, C and David, M and Panet-Raymond, V and Abdulkarim, B and Hijal, T}, title = {Targeted Intraoperative Radiation Therapy during Breast-Conserving Surgery for Patients with Early Stage Breast Cancer: A Phase II Single Center Prospective Trial.}, journal = {Advances in radiation oncology}, volume = {8}, number = {5}, pages = {101236}, pmid = {37408681}, issn = {2452-1094}, abstract = {PURPOSE: Patients with early stage breast cancer (ESBC) are conventionally treated with breast-conserving surgery (BCS) followed by whole-breast external beam radiation therapy (EBRT). The emergence of targeted intraoperative radiation therapy (TARGIT) with Intrabeam has been used as a therapeutic alternative for patients with risk-adapted ESBC. Here we present our radiation therapy toxicities (RTT), postoperative complications (PC), and short-term outcomes of the prospective phase II trial at the McGill University Health Center.

METHODS AND MATERIALS: Patients aged ≥50 years with biopsy-proven hormone receptor-positive, grade 1 or 2, invasive ductal carcinoma of the breast, cT1N0, were eligible for the study. Enrolled patients underwent BCS followed by immediate TARGIT of 20 Gy in 1 fraction. Upon final pathology, patients with low-risk breast cancer (LRBC) received no further EBRT, and those with high-risk breast cancer (HRBC) received further 15 to 16 fractions of whole breast EBRT. HRBC criteria included pathologic tumor size >2 cm, grade 3, positive lympho-vascular invasion, multifocal disease, close margins (<2 mm), or positive nodal disease.

RESULTS: A total of 61 patients with ESBC were enrolled in the study; upon final pathology, 40 (65.6%) had LRBC, and 21 (34.4%) had HRBC. The median follow-up was 3.9 years. The most common HRBC criteria were close margins in 66.6% (n = 14) and lymphovascular invasion in 28.6% (n = 6). No grade 4 RTT were observed in either group. The most common PC were seroma and cellulitis for both groups. The rate of locoregional recurrence was 0% in both groups. The overall survival in LRBC was 97.5% and in HRBC 95.2% with no significant differences. Deaths were nonbreast cancer related.

CONCLUSIONS: In patients with ESBC undergoing BCS, the use of TARGIT shows low rates of RTT and PC complications. Moreover, our short-term outcomes show no significant difference at 3.9 years median follow-up for locoregional recurrence or overall survival between groups of patients receiving TARGIT alone or TARGIT followed by EBRT. Of all patients, 34.4% required further EBRT, most commonly due to close margins.}, } @article {pmid37408309, year = {2023}, author = {Ji, H and Englmaier, F and Morigny, P and Giroud, M and Gräsle, P and Brings, S and Szendrödi, J and Berriel Diaz, M and Plettenburg, O and Herzig, S and Rohm, M}, title = {Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {8}, pages = {2408-2421}, pmid = {37408309}, issn = {1525-0024}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Adipose Tissue/metabolism ; *AMP-Activated Protein Kinases/metabolism ; Cachexia/drug therapy/etiology/metabolism ; *Neoplasms/complications/metabolism ; Peptides/pharmacology ; Pharmaceutical Preparations/metabolism ; Quality of Life ; }, abstract = {Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.}, } @article {pmid37405478, year = {2023}, author = {Rong, XC and Kang, YH and Shi, GF and Ren, JL and Liu, YH and Li, ZG and Yang, G}, title = {The use of mammography-based radiomics nomograms for the preoperative prediction of the histological grade of invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {13}, pages = {11635-11645}, pmid = {37405478}, issn = {1432-1335}, mesh = {Humans ; *Nomograms ; Retrospective Studies ; Logistic Models ; Mammography ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Accurate prediction of the grade of invasive ductal carcinoma (IDC) before treatment is vital for individualized therapy and improving patient outcomes. This study aimed to develop and validate a mammography-based radiomics nomogram that would incorporate the radiomics signature and clinical risk factors in the preoperative prediction of the histological grade of IDC.

METHODS: The data of 534 patients from our hospital with pathologically confirmed IDC (374 in the training cohort and 160 in the validation cohort) were retrospectively analyzed. A total of 792 radiomics features were extracted from the patients' craniocaudal and mediolateral oblique view images. A radiomics signature was generated using the least absolute shrinkage and selection operator method. Multivariate logistic regression was adopted to establish a radiomics nomogram, the utility of which was evaluated using a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA).

RESULTS: The radiomics signature was found to have a significant correlation with histological grade (P < 0.01), but the efficacy of the model is limited. The radiomics nomogram, which incorporated the radiomics signature and spicule sign into mammography, showed good consistency and discrimination in both the training cohort [area under the curve (AUC) = 0.75] and the validation cohort (AUC = 0.75). The calibration curves and DCA demonstrated the clinical usefulness of the proposed radiomics nomogram model.

CONCLUSIONS: A radiomics nomogram based on the radiomics signature and spicule sign can be used to predict the histological grade of IDC and assist in clinical decision-making for patients with IDC.}, } @article {pmid37404109, year = {2023}, author = {Yang, L and Li, XM and Zhang, MN and Yao, J and Song, B}, title = {Nomogram Models for Distinguishing Intraductal Carcinoma of the Prostate From Prostatic Acinar Adenocarcinoma Based on Multiparametric Magnetic Resonance Imaging.}, journal = {Korean journal of radiology}, volume = {24}, number = {7}, pages = {668-680}, pmid = {37404109}, issn = {2005-8330}, mesh = {Male ; Humans ; Prostate/diagnostic imaging/pathology ; *Multiparametric Magnetic Resonance Imaging ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Nomograms ; Prostatectomy ; Retrospective Studies ; *Prostatic Neoplasms/pathology ; *Carcinoma, Acinar Cell/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: To compare multiparametric magnetic resonance imaging (MRI) features of intraductal carcinoma of the prostate (IDC-P) with those of prostatic acinar adenocarcinoma (PAC) and develop prediction models to distinguish IDC-P from PAC and IDC-P with a high proportion (IDC ≥ 10%, hpIDC-P) from IDC-P with a low proportion (IDC < 10%, lpIDC-P) and PAC.

MATERIALS AND METHODS: One hundred and six patients with hpIDC-P, 105 with lpIDC-P and 168 with PAC, who underwent pretreatment multiparametric MRI between January 2015 and December 2020 were included in this study. Imaging parameters, including invasiveness and metastasis, were evaluated and compared between the PAC and IDC-P groups as well as between the hpIDC-P and lpIDC-P subgroups. Nomograms for distinguishing IDC-P from PAC, and hpIDC-P from lpIDC-P and PAC, were made using multivariable logistic regression analysis. The discrimination performance of the models was assessed using the receiver operating characteristic area under the curve (ROC-AUC) in the sample, where the models were derived from without an independent validation sample.

RESULTS: The tumor diameter was larger and invasive and metastatic features were more common in the IDC-P than in the PAC group (P < 0.001). The distribution of extraprostatic extension (EPE) and pelvic lymphadenopathy was even greater, and the apparent diffusion coefficient (ADC) ratio was lower in the hpIDC-P than in the lpIDC-P group (P < 0.05). The ROC-AUCs of the stepwise models based solely on imaging features for distinguishing IDC-P from PAC and hpIDC-P from lpIDC-P and PAC were 0.797 (95% confidence interval, 0.750-0.843) and 0.777 (0.727-0.827), respectively.

CONCLUSION: IDC-P was more likely to be larger, more invasive, and more metastatic, with obviously restricted diffusion. EPE, pelvic lymphadenopathy, and a lower ADC ratio were more likely to occur in hpIDC-P, and were also the most useful variables in both nomograms for predicting IDC-P and hpIDC-P.}, } @article {pmid37402637, year = {2023}, author = {Shulder, S and Tamma, PD and Fiawoo, S and Dzintars, K and Escobar, D and Livorsi, DJ and Malani, AN and Palacio, D and Spivak, ES and Zimmerman, M and Bork, JT}, title = {Infectious Diseases Consultation Associated with Reduced Mortality in Gram-Negative Bacteremia.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciad383}, pmid = {37402637}, issn = {1537-6591}, abstract = {Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of ID consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4,861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.}, } @article {pmid37397657, year = {2023}, author = {Godbole, M and Wani, K and Zia, S and Dabak, V}, title = {Carcinoma En Cuirasse: A Rare but Striking Cutaneous Manifestation of Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e39838}, pmid = {37397657}, issn = {2168-8184}, abstract = {Carcinoma en cuirasse is a rare cutaneous metastatic presentation of breast cancer with a poor prognosis. We report a female in her 70s with a prior history of left breast ductal carcinoma in situ status post-radiation and lumpectomy who presented with skin thickening of the left breast and a few solid masses in bilateral breasts. Biopsy showed invasive ductal carcinoma of the left breast (estrogen receptor [ER]/progesterone receptor positive [PR], human epidermal growth factor receptor-2 [HER2] negative) and ductal carcinoma in situ of the right breast (ER/PR positive). She underwent a right breast lumpectomy; however, the left breast mastectomy was aborted due to the worsening of her skin findings on preoperative examination. A skin biopsy revealed poorly differentiated invasive ductal carcinoma. She was diagnosed with stage 4 breast cancer, specifically carcinoma en cuirasse. Systemic treatment was initiated, followed by a left breast mastectomy. A surgical biopsy was HER2-positive, and therefore anti-HER2 therapy was given. She remains on maintenance therapy with an excellent response at present.Any unexplained skin findings in breast cancer patients should prompt consideration of carcinoma en cuirasse. With ongoing treatment advances, many newer therapy options are available for metastatic breast cancer. Based on our case, we think that patients with this disease can have better outcomes.}, } @article {pmid37387350, year = {2023}, author = {Jin, M and Wang, Y and Zhou, T and Li, W and Wen, Q}, title = {Norepinephrine/β2-Adrenergic Receptor Pathway Promotes the Cell Proliferation and Nerve Growth Factor Production in Triple-Negative Breast Cancer.}, journal = {Journal of breast cancer}, volume = {26}, number = {3}, pages = {268-285}, pmid = {37387350}, issn = {1738-6756}, support = {81273923//National Natural Science Foundation of China/China ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC.

METHODS: The expression levels of the β2-adrenergic receptor (β2-AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2-AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2-AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis.

RESULTS: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2-AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the co-culture assay, the sympathetic adrenergic NE/β2-AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth.

CONCLUSION: These results suggest that NE/β2-AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.}, } @article {pmid37386078, year = {2023}, author = {Szekeres, H and Halperin, E and Kende, A and Saguy, T}, title = {The aversive bystander effect whereby egalitarian bystanders overestimate the confrontation of prejudice.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10538}, pmid = {37386078}, issn = {2045-2322}, mesh = {Humans ; Black or African American ; *Prejudice/ethnology/prevention & control ; United States ; Hungary ; *Human Rights ; Motivation ; Self-Assessment ; Social Behavior ; Roma ; Hispanic or Latino ; Islam ; }, abstract = {Everyday expression of prejudice continues to pose a social challenge across societies. We tend to assume that to the extent people are egalitarian, they are more likely to confront prejudice-but this might not necessarily be the case. We tested this assumption in two countries (US and Hungary) among majority members of society, using a behavioral paradigm for measuring confronting. Prejudice was directed at various outgroup minority individuals (African Americans, Muslims and Latinos in the US, and Roma in Hungary). Across four experiments (N = 1116), we predicted and found that egalitarian (anti-prejudiced) values were only associated with hypothetical confronting intentions, but not with actual confronting, and stronger egalitarians were more likely to overestimate their confronting than weaker egalitarians-to the point that while intentions differed, the actual confronting rate of stronger and weaker egalitarians were similar. We also predicted and found that such overestimation was associated with internal (and not external) motivation to respond without prejudice. We also identified behavioral uncertainty (being uncertain how to intervene) as a potential explanation for egalitarians' overestimation. The implications of these findings for egalitarians' self-reflection, intergroup interventions, and research are discussed.}, } @article {pmid37385107, year = {2023}, author = {Chen, J and Gao, P and Xiao, W and Cheng, G and Krishna, S and Wang, J and Wong, YK and Wang, C and Gu, L and Yang, DH and Wang, J}, title = {Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {70}, number = {}, pages = {100978}, doi = {10.1016/j.drup.2023.100978}, pmid = {37385107}, issn = {1532-2084}, mesh = {Humans ; Plasmodium falciparum/genetics ; Multiomics ; Drug Resistance/genetics ; Protozoan Proteins/genetics/pharmacology/therapeutic use ; *Artemisinins/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; Mutation ; }, abstract = {AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation.

METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain.

RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages.

CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.}, } @article {pmid37383682, year = {2023}, author = {Ricks-Santi, LJ and Fredenburg, K and Rajaei, M and Esnakula, A and Naab, T and McDonald, JT and Kanaan, Y}, title = {Characterization of GATA3 and Mammaglobin in breast tumors from African American Women.}, journal = {Archives of microbiology & immunology}, volume = {7}, number = {1}, pages = {18-28}, pmid = {37383682}, issn = {2572-9365}, support = {R15 CA239100/CA/NCI NIH HHS/United States ; }, abstract = {GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.}, } @article {pmid37383152, year = {2023}, author = {Shirian, F and Kheradmand, P and Ranjbari, N and Shahbazian, H and Latifi, SM}, title = {Immunoexpression of the GCDFP-15 Marker in Different Grades of Breast Carcinoma.}, journal = {Iranian journal of pathology}, volume = {18}, number = {1}, pages = {75-81}, pmid = {37383152}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: During the last decade, biological markers of breast cancer have been considered to predict the degree of histology, behavior, and extent of tumor invasion and the possibility of lymph node involvement. The aim of this study was to evaluate the expression of GCDFP-15 in different grades of invasive ductal carcinoma, as the most common type of breast cancer.

METHODS: In this retrospective study, paraffin blocks of tumors of 60 breast cancer patients registered in the histopathology laboratory of Imam Khomeini Hospital in Ahvaz between 2019 and 2020 were reviewed. Information on grade, invasion, stage and lymph node involvement was extracted from the pathology reports and immunohistochemical staining for GCDFP-15 was performed. Data were analyzed by SPSS 22.

RESULTS: GCDFP-15 marker expression was observed in 20 out of 60 breast cancer patients (33.3%). GCDFP-15 staining intensity was weak in 7 cases (35%), moderate in 8 cases (40%), and strong in 5 cases (25%). The patient's age and sex showed no significant relationship with the expression of GCDFP-15 and intensity of staining. Expression of the GCDFP-15 marker was correlated significantly with tumor grade, stage, and vascular invasion (P<0.05)) and its expression was higher in tumors with a lower grade, less depth of invasion, and no vascular invasion but unrelated to perineural invasion, lymph node involvement, and tumor size. The intensity of staining for GCDFP-15 showed significant relationship with the tumor grade (P<0.0001) but unrelated to the other factors.

CONCLUSION: GCDFP-15 marker may be significantly associated with tumor grade, depth of invasion, and vascular invasion, thus can be used as a prognostic marker.}, } @article {pmid37382756, year = {2023}, author = {Abouegylah, M and Elemary, O and Ahmed, AA and ElFeky, AM and Fayed, H and Gawish, M and Mahmoud, AA and Gawish, A}, title = {Impact of breath hold on regional nodal irradiation and heart volume in field in left breast cancer adjuvant irradiation.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {37382756}, issn = {1699-3055}, abstract = {PURPOSE: Compared to the free-breathing technique, adjuvant left breast irradiation after breast-conserving surgery or mastectomy using the breath-hold method significantly reduces the heart mean dose, Left anterior descending artery, and ipsilateral lung doses. Movement with deep inspiration may also reduce heart volume in the field and regional node doses.

MATERIALS AND METHODS: Pre-radiotherapy planning CT was performed in the free-breathing, and breath-hold techniques using RPM, demographic information, clinicopathological data, heart volume in the field, heart mean dose, LAD mean dose, and regional nodal doses were calculated in both free breathing and DIBH. Fifty patients with left breast cancer receiving left breast adjuvant radiation were enrolled.

RESULTS: There was no significant difference in axillary LN coverage between the two techniques, except for SCL maximum dose, Axilla I node maximum dose, and Axilla II minimum dose in favor of the breath hold technique. The mean age was 47.54 years, 78% had GII IDC, 66% had positive LVSI results, and 74% of patients had T2. The breath hold strategy resulted in considerably decreased mean heart dose (p = 0.000), LAD dose (p = 0.000), ipsilateral lung mean dose (p = 0.012), and heart volume if the field (p = 0.013). The mean cardiac dosage and the dose of the LAD were significantly correlated (p = 0.000, R = 0.673). Heart volume in the field and heart mean dosage was not significantly correlated (p = 0.285, r = - 0.108).

CONCLUSION: When compared to free breathing scans, DIBH procedures result in considerably reduced dosage to the OAR and no appreciable changes in dose exposure to regional lymph node stations in patients with left-sided breast cancer.}, } @article {pmid37377907, year = {2023}, author = {Ding, R and Wang, Y and Fan, J and Tian, Z and Wang, S and Qin, X and Su, W and Wang, Y}, title = {Identification of immunosuppressive signature subtypes and prognostic risk signatures in triple-negative breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1108472}, pmid = {37377907}, issn = {2234-943X}, abstract = {PURPOSE: Immune checkpoint blockade (ICB) therapy has transformed the treatment of triple-negative breast cancer (TNBC) in recent years. However, some TNBC patients with high programmed death-ligand 1 (PD-L1) expression levels develop immune checkpoint resistance. Hence, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to construct prognostic models of patient survival outcomes in order to understand biological mechanisms operating within the tumor microenvironment.

PATIENTS AND METHODS: RNA sequence (RNA-seq) data from 303 TNBC samples were analyzed using an unsupervised cluster analysis approach to reveal distinctive cellular gene expression patterns within the TNBC tumor microenvironment (TME). A panel of T cell exhaustion signatures, immunosuppressive cell subtypes and clinical features were correlated with the immunotherapeutic response, as assessed according to gene expression patterns. The test dataset was then used to confirm the occurrence of immune depletion status and prognostic features and to formulate clinical treatment recommendations. Concurrently, a reliable risk prediction model and clinical treatment strategy were proposed based on TME immunosuppressive signature differences between TNBC patients with good versus poor survival status and other clinical prognostic factors.

RESULTS: Significantly enriched TNBC microenvironment T cell depletion signatures were detected in the analyzed RNA-seq data. A high proportion of certain immunosuppressive cell subtypes, 9 inhibitory checkpoints and enhanced anti-inflammatory cytokine expression profiles were noted in 21.4% of TNBC patients that led to the designation of this group of immunosuppressed patients as the immune depletion class (IDC). Although IDC group TNBC samples contained tumor-infiltrating lymphocytes present at high densities, IDC patient prognosis was poor. Notably, PD-L1 expression was relatively elevated in IDC patients that indicated their cancers were resistant to ICB treatment. Based on these findings, a set of gene expression signatures predicting IDC group PD-L1 resistance was identified then used to develop risk models for use in predicting clinical therapeutic outcomes.

CONCLUSION: A novel TNBC immunosuppressive tumor microenvironment subtype associated with strong PD-L1 expression and possible resistance to ICB treatment was identified. This comprehensive gene expression pattern may provide fresh insights into drug resistance mechanisms for use in optimizing immunotherapeutic approaches for TNBC patients.}, } @article {pmid37371442, year = {2023}, author = {Maggi, G and Vitale, C and Delle Curti, A and Amboni, M and Santangelo, G}, title = {Unawareness of Apathy in Parkinson's Disease: The Role of Executive Dysfunction on Symptom Recognition.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371442}, issn = {2076-3425}, abstract = {Altered self-awareness or anosognosia may impact patients' everyday life by interfering with their safe and independent functioning. Symptom awareness has been linked to executive dysfunctions caused by damage to frontal regions. Apathy is a frequent neuropsychiatric manifestation of Parkinson's disease (PD) and is considered a consequence of altered functioning of cortico-subcortical circuitries connecting the prefrontal cortex (PFC) with the basal ganglia. Thus, apathetic PD patients may be not be fully aware of their condition due to shared neuropathophysiological mechanisms. The present study aimed to explore the awareness of apathy in PD patients by comparing the self-reported evaluations with their caregivers' ratings. Moreover, we explored the clinical predictors of possible discrepancies and their consequences on patients' self-reported evaluation of quality of life (QoL). We found a fair agreement between patients' self-reports and caregivers' ratings on apathy scores, with patients reporting less severe apathetic symptoms, especially those related to executive and auto-activation processing, compared to their caregivers' reports. Executive functioning was found to mediate the relationship between disease stage and awareness of the apathetic state. Awareness of executive apathy impacted patients' self-reported QoL. Therefore, PD patients might be unaware of their apathetic symptoms, especially those with worse executive functioning, which plays a key role in metacognitive processes such as self-monitoring and error detection. Anosognosia for apathy in PD patients may affect their QoL perception and leads to misleading self-report evaluations that delay diagnosis and treatment.}, } @article {pmid37370954, year = {2023}, author = {Abubakar, S and More, S and Tag, N and Olabinjo, A and Isah, A and Lawal, I}, title = {Differences in Tumour Aggressiveness Based on Molecular Subtype and Race Measured by [[18]F]FDG PET Metabolic Metrics in Patients with Invasive Carcinoma of the Breast.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {37370954}, issn = {2075-4418}, abstract = {Breast cancer in women of African descent tends to be more aggressive with poorer prognosis. This is irrespective of the molecular subtype. [[18]F]FDG PET/CT metrics correlate with breast cancer aggressiveness based on molecular subtype. This study investigated the differences in [[18]F]FDG PET/CT metrics of locally advanced invasive ductal carcinoma (IDC) among different racial groups and molecular subtypes. Qualitative and semiquantitative readings of [[18]F]FDG PET/CT acquired in women with locally advanced IDC were performed. Biodata including self-identified racial grouping and histopathological data of the primary breast cancer were retrieved. Statistical analysis for differences in SUVmax, MTV and TLG of the primary tumour and the presence of regional and distant metastases was conducted based on molecular subtype and race. The primary tumour SUVmax, MTV, TLG and the prevalence of distant metastases were significantly higher in Black patients compared with other races (p < 0.05). The primary tumour SUVmax and presence of distant metastases in the luminal subtype and the primary tumour SUVmax and TLG in the basal subtype were significantly higher in Black patients compared with other races (p < 0.05). The significantly higher PET parameters in Black patients with IDC in general and in those with luminal and basal carcinoma subtypes suggest a more aggressive disease phenotype in this race.}, } @article {pmid37369698, year = {2023}, author = {Meng, X and Morita, M and Kuba, S and Hayashi, H and Otsubo, R and Matsumoto, M and Yamanouchi, K and Kobayashi, K and Soyama, A and Hidaka, M and Kanetaka, K and Nagayasu, T and Eguchi, S}, title = {Association of quantitative analysis of intratumoral reduced E-cadherin expression with lymph node metastasis and prognosis in patients with breast cancer.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10434}, pmid = {37369698}, issn = {2045-2322}, mesh = {Female ; Humans ; Biomarkers, Tumor/analysis ; *Breast Neoplasms/pathology ; Cadherins/metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Prognosis ; }, abstract = {Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.}, } @article {pmid37364826, year = {2023}, author = {Wang, Y and Teramoto, Y and Miyamoto, H}, title = {Comedonecrosis within conventional prostatic adenocarcinoma vs. intraductal carcinoma of the prostate: their clinical significance is not comparable.}, journal = {Human pathology}, volume = {138}, number = {}, pages = {112-120}, doi = {10.1016/j.humpath.2023.06.011}, pmid = {37364826}, issn = {1532-8392}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; Prognosis ; Neoplasm Grading ; Prostatectomy ; Necrosis/pathology ; }, abstract = {It remains controversial if Gleason grade should be assigned to intraductal carcinoma of the prostate (IDC-P) and if the prognostic value of comedonecrosis associated with IDC-P is equivalent to that in conventional/invasive prostatic adenocarcinoma (CPA) as a Gleason grade 5 pattern. We herein assessed radical prostatectomy findings and postoperative outcomes in 287 patients with CPA exhibiting any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of necrosis within CPA and/or IDC-P: Cohort-1) no necrosis in CPA/IDC-P (n = 179; 62.4%); Cohort-2) necrosis only in CPA (n = 25; 8.7%); Cohort-3) necrosis only in IDC-P (n = 62; 21.6%); and Cohort-4) necrosis in both CPA and IDC-P (n = 21; 7.3%). Univariate analysis revealed patients with necrosis only in IDC-P (P < .001) or both CPA and IDC-P (P = .001) had a higher risk of progression than those with necrosis only in CPA, while the prognosis was comparable between the no necrosis group vs. the CPA only necrosis group (P = .680) or the IDC-P only necrosis group vs. the CPA/IDC-P necrosis group (P = .715). In a subgroup of patients exhibiting IDC-P (n = 198), the presence of IDC-P necrosis was still associated with a significantly higher progression risk, compared with CPA necrosis only. In multivariable analysis, necrosis only in IDC-P (vs. necrosis only in CPA) showed significantly worse progression-free survival (HR = 3.193, P = .003). IDC-P necrosis, as an independent predictor, was thus found to be associated with significantly worse oncologic outcomes, compared with necrosis only in CPA, and might therefore be better not to be simply considered as a grade 5 pattern.}, } @article {pmid37363526, year = {2023}, author = {Kara Tahhan, N and Abou Azan, A and Jomaa Al Ali, I and Abdul Aziz, J and Sara, S}, title = {Cutaneous metastases as a primary manifestation of invasive ductal carcinoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {3062-3065}, pmid = {37363526}, issn = {2049-0801}, abstract = {UNLABELLED: Cutaneous metastases as the first sign of invasive ductal carcinoma are not common. The ambiguous presentation of asymptomatic lesions may result in various diagnoses including dermatologic causes. Early diagnosis is essential in such cases.

CASE PRESENTATION: A 43-year-old woman with no risk factors for developing breast cancer at a young age was diagnosed with invasive ductal carcinoma of the left breast after dermatologic complaints of diffuse lesions on the left-back and right subclavian region. The patient remained asymptomatic except for the recent cutaneous presentation, which did not arouse much suspicion.

CONCLUSION: Cutaneous metastases of breast cancer remain uncommon, but at the same time represent a poor prognosis for the patient, and when they do occur, treatment options are limited. The delay in taking the proper diagnostic measures in such cases imposes a need to adopt a wider perspective when dealing with the possible occurrence of advanced disease. This also adds up to the importance of breast self-examination by women at a young age and full examination by physicians, especially when they encounter a misguiding presentation.}, } @article {pmid37363420, year = {2023}, author = {Singh, S and Singh, AL and Pal, KK and Reddy, KK and Gangadhara, K and Dey, R and Mahatma, MK and Verma, A and Kumar, N and Patel, CB and Thawait, LK and Ahmed, S and Navapara, R and Rani, K and Kona, P}, title = {Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.}, journal = {Physiology and molecular biology of plants : an international journal of functional plant biology}, volume = {29}, number = {5}, pages = {725-737}, pmid = {37363420}, issn = {0971-5894}, abstract = {UNLABELLED: Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe[2+]) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml[-1]), carotenoid accumulation (1.96-2.08 µg ml[-1]), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm[-1]) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.}, } @article {pmid37363122, year = {2023}, author = {Wani, K and Patel, K and Dabak, V}, title = {Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40871}, pmid = {37363122}, issn = {2168-8184}, abstract = {Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.}, } @article {pmid37355360, year = {2023}, author = {Fatehi, P and Mahboubi-Fooladi, Z and Dastmardi, M and Jafarzadeh Esfehani, R and Khameneh Bagheri, A}, title = {The correlation between imaging findings and breast cancer cell receptors status.}, journal = {Journal of medical imaging and radiation sciences}, volume = {54}, number = {3}, pages = {446-450}, doi = {10.1016/j.jmir.2023.05.044}, pmid = {37355360}, issn = {1876-7982}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/diagnosis ; Cross-Sectional Studies ; Mammography ; Receptors, Estrogen/metabolism ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: Breast cancer is the most common malignancy among women, and subtypes are mainly defined based on hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The relationship between breast cancer subtypes and imaging features in mammography and sonography has been studied but the results are controversial. The purpose of this study was to determine the relationship between the hormonal receptor status of breast tumors and the radiologic feature of the tumors on mammography and sonography.

METHODS: Eighty patients with breast cancer enrolled in this cross-sectional study. ER, PR, and HER2 determined by immunohistochemistry. Every patient underwent mammography and sonography before the biopsy. We evaluated the relationship between the hormonal receptor status and radiographic features of tumors on breast sonography and mammography.

RESULTS: The majority of the patients (n=75 (93.8%)) were diagnosed with invasive ductal carcinoma (IDC). The mean and standard deviation of the age was 49 ± 9 years. There was no significant relationship between the hormonal receptor status and the sonographic margin and shape (P>0.05). However, PR (P=0.002) and ER (P=0.001) status were significantly correlated with posterior features on sonography. ER-positive patients were more likely to have indistinct or speculated masses on mammography (P=0.017). Irregular or oval masses on mammography were higher in patients with ER (p=0.032).

CONCLUSION: There was a significant correlation between PR and ER status and posterior features on sonography. Positive ER was associated with indistinct or speculated masses on mammography, as well as irregular or oval masses.}, } @article {pmid37354822, year = {2023}, author = {Farho, MA and Sawas, MN and Alnajjar, M and Al-Kurdi, MA and Nawlo, A and Alloush, H}, title = {Subtrochanteric fracture in previously treated breast cancer patient handled by proximal femoral nail: A case report.}, journal = {International journal of surgery case reports}, volume = {108}, number = {}, pages = {108411}, pmid = {37354822}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast cancer (BC) is the most common and high mortality rate cancer in females. The main complication of BC is metastases, where bone metastases (BM) are present in 90 % of women with distant metastases and commonly recurrence after BC therapy. However, treatment options are numerous, and improving patients' quality of life (QoL) is a priority.

PRESENTATION OF CASE: A 58-year-old female patient presented to the emergency department with pain and movement restriction in the right lower extremity after minor trauma. Clinical history included a surgically resected BC eight years ago, besides chemotherapy and radiotherapy. After clinical and radiographic examination, we encountered a subtrochanteric femoral fracture although the patient is in the end stage, the multidisciplinary team discussed the surgery option with the patient and eventually internally fixed the fracture.

DISCUSSION: Subtrochanteric femur fractures represent a challenging orthopedic issue, ranging from 10 % to 34 % of all hip fractures. Hence, after a detailed discussion, the proximal femoral nail (PFN) was the procedure of choice acording to the patient's preferences and tumor prognosis. Proximal femoral metastasis treatment aims to improve the quality of life (QoL), alleviate bone pain, and rehabilitate skeletal function.

CONCLUSION: In this case report, we highlight the surgical decision consequences for a patient with end-stage cancer, as it may put their life at risk or improve their QoL, likewise the patient in this report.}, } @article {pmid37354223, year = {2023}, author = {Liu, Y and Yu, T}, title = {Clinicopathological characteristics and prognosis of triple-negative breast cancer invasive ductal carcinoma with ductal carcinoma in situ.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {13}, pages = {11181-11191}, pmid = {37354223}, issn = {1432-1335}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Triple Negative Breast Neoplasms/therapy ; Retrospective Studies ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/therapy/pathology ; Prognosis ; }, abstract = {PURPOSE: The purpose of this study is to compare and analyze the clinicopathological characteristics and prognosis of patients with invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) and invasive ductal carcinoma (IDC) in triple-negative breast cancer (TNBC), and to explore the factors affecting the prognosis, so as to provide new ideas for clinical diagnosis and treatment of these patients.

METHODS: The patients with TNBC underwent surgery in the Department of Breast Surgery of Harbin Medical University Cancer Hospital from October 2012 to December 2018 were retrospectively analyzed and divided into IDC-DCIS group and IDC group. The clinicopathological characteristics and prognosis of the two groups were compared. P < 0.05 was considered statistically significant.

RESULTS: A total of 358 patients were enrolled. There were significant differences in age (P = 0.002), family history (P = 0.016), menopausal status (P = 0.003), KI-67% (P < 0.001), lymphovascular invasion (P = 0.010), histologic grade of IDC (P < 0.001) and multifocal (P < 0.001) between the two groups. The disease-free survival (DFS) of the IDC-DCIS group was better than that of the IDC group (the 5-year DFS was 87.9% vs. 82.6%, P = 0.045), but the overall survival (OS) of the two groups was not statistically significant (the 5-year OS was 96.2% vs. 96.0%, P = 0.573). In addition, the coexistence of DCIS (P = 0.030), lymph node pathologic stage (P = 0.001), tumor location (P = 0.011), and adjuvant chemotherapy (P < 0.001) were independent prognostic factors for DFS.

CONCLUSION: In TNBC, the IDC-DCIS group had less invasive biological characteristics. The DFS of the IDC-DCIS group was better than that of the IDC group, but there was no statistical difference in OS between the two groups. In addition, the coexistence of DCIS, lymph node stage, tumor location and adjuvant chemotherapy may be independent prognostic factors for DFS.}, } @article {pmid37353557, year = {2023}, author = {Thomas, A and Reis-Filho, JS and Geyer, CE and Wen, HY}, title = {Rare subtypes of triple negative breast cancer: Current understanding and future directions.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {55}, pmid = {37353557}, issn = {2374-4677}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, abstract = {Rare subtypes of triple-negative breast cancers (TNBC) are a heterogenous group of tumors, comprising 5-10% of all TNBCs. Despite accounting for an absolute number of cases in aggregate approaching that of other less common, but well studied solid tumors, rare subtypes of triple-negative disease remain understudied. Low prevalence, diagnostic challenges and overlapping diagnoses have hindered consistent categorization of these breast cancers. Here we review epidemiology, histology and clinical and molecular characteristics of metaplastic, triple-negative lobular, apocrine, adenoid cystic, secretory and high-grade neuroendocrine TNBCs. Medullary pattern invasive ductal carcinoma no special type, which until recently was a considered a distinct subtype, is also discussed. With this background, we review how applying biological principals often applied to study TNBC no special type could improve our understanding of rare TNBCs. These could include the utilization of targeted molecular approaches or disease agnostic tools such as tumor mutational burden or germline mutation-directed treatments. Burgeoning data also suggest that pathologic response to neoadjuvant therapy and circulating tumor DNA have value in understanding rare subtypes of TNBC. Finally, we discuss a framework for advancing disease-specific knowledge in this space. While the conduct of randomized trials in rare TNBC subtypes has been challenging, re-envisioning trial design and technologic tools may offer new opportunities. These include embedding rare TNBC subtypes in umbrella studies of rare tumors, retrospective review of contemporary trials, prospective identification of patients with rare TNBC subtypes entering on clinical trials and querying big data for outcomes of patients with rare breast tumors.}, } @article {pmid37351769, year = {2023}, author = {Byrd, BK and Wells, WA and Strawbridge, RR and Barth, CW and Samkoe, KS and Gibbs, SL and Davis, SC}, title = {Evaluating Receptor-Specific Fresh Specimen Staining for Tumor Margin Detection in Clinical Breast Specimens.}, journal = {Molecular imaging and biology}, volume = {}, number = {}, pages = {}, pmid = {37351769}, issn = {1860-2002}, support = {R01CA188491/NH/NIH HHS/United States ; }, abstract = {PURPOSE: Reliable and rapid identification of tumor in the margins of breast specimens during breast-conserving surgery to reduce repeat surgery rates is an active area of investigation. Dual-stain difference imaging (DDSI) is one of many approaches under evaluation for this application. This technique aims to topically apply fluorescent stain pairs (one targeted to a receptor-of-interest and the other a spectrally distinct isotype), image both stains, and compute a normalized difference image between the two channels. Prior evaluation and optimization in a variety of preclinical models produced encouraging diagnostic performance. Herein, we report on a pilot clinical study which evaluated HER2-targeted DDSI on 11 human breast specimens.

PROCEDURES: Gross sections from 11 freshly excised mastectomy specimens were processed using a HER2-receptor-targeted DDSI protocol shortly after resection. After staining with the dual-probe protocol, specimens were imaged on a fluorescence scanner, followed by tissue fixation for hematoxylin and eosin and anti-HER2 immunohistochemical staining. Receiver operator characteristic curves and area under the curve (AUC) analysis were used to assess diagnostic performance of the resulting images. Performance values were also compared to expression level determined from IHC staining.

RESULTS: Eight of the 11 specimens presented with distinguishable invasive ductal carcinoma and/or were not affected by an imaging artifact. In these specimens, the DDSI technique provided an AUC = 0.90 ± 0.07 for tumor-to-adipose tissue and 0.81 ± 0.15 for tumor-to-glandular tissue, which was significantly higher than AUC values recovered from images of the targeted probe alone. DDSI values and diagnostic performance did not correlate with HER2 expression level, and tumors with low HER2 expression often produced high AUC, suggesting that even the low expression levels were enough to help distinguish tumor.

CONCLUSIONS: The results from this preliminary study of rapid receptor-specific staining in human specimens were consistent with prior preclinical results and demonstrated promising diagnostic potential.}, } @article {pmid37350603, year = {2023}, author = {Ruiz Ramos, J and Calderón Hernanz, B and Castellanos Clemente, Y and Bonete Sánchez, M and Vallve Alcon, E and Santolaya Perrin, MªR and García Martín, MªÁ and de Lorenzo Pinto, A and Real Campaña, JM and Ramos Rodríguez, J and Calzón Blanco, C and García Peláez, M and Alonso Ramos, H and Altimiras Ruiz, J and Sempere Serrano, P and Martín Cerezuela, M and Periañez Parraga, L and Juanes Borrego, AM and Somoza Fernández, B and Rodríguez Camacho, JM and Puig Campmany, M and Miguens Blanco, I and Tomás Vecina, S and Nadal Galmes, C and Povar Marco, J}, title = {Pharmacist care in hospital emergency departments: a consensus paper from the Spanish hospital pharmacy and emergency medicine associations.}, journal = {Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias}, volume = {35}, number = {3}, pages = {205-217}, pmid = {37350603}, issn = {2386-5857}, mesh = {Humans ; Pharmacists ; Consensus ; *Pharmacy Service, Hospital ; Emergency Service, Hospital ; *Emergency Medicine ; Hospitals ; }, abstract = {OBJECTIVES: To draft a list of actions and quality indicators for pharmacist care in hospital emergency departments, based on consensus among a panel of experts regarding which actions to prioritize in this setting.

MATERIAL AND METHODS: A panel of experts from the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Emergency Medicine (SEMES) evaluated a preliminary list of potential actions and quality of care indicators. The experts used a questionnaire to assess the proposals on the basis of available evidence. In the first round, each expert individually assessed the importance of each proposed action based on 4 dimensions: evidence base, impact on clinical response and patient safety, ease of implementation, and priority. In the second round the experts attended a virtual meeting to reach consensus on a revised list of proposals; suggestions and comments that had been made anonymously in the first round were included. The group then prioritized each action as basic, intermediate, or advanced.

RESULTS: The experts evaluated a total of 26 potential actions and associated quality indicators. No items were eliminated in the analysis of scores and comments from the first round. After the second round, 25 actions survived. Nine were considered basic, 10 intermediate, and 6 advanced.

CONCLUSION: The expert panel's list of pharmacist actions and care quality indicators provides a basis for developing a pharmacist care program in Spanish emergency departments on 3 levels of priority. The list can serve as a guide to pharmacists, managers, physicians, and nurses involved in the effort to improve drug therapy in this hospital setting.}, } @article {pmid37344429, year = {2023}, author = {Kishimoto, K and Shibagaki, K and Araki, A and Murakami, K and Takahashi, Y and Kotani, S and Oka, A and Yazaki, T and Fukuba, N and Mishima, Y and Oshima, N and Kawashima, K and Ishimura, N and Kadota, K and Ishihara, S}, title = {Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.1965-23}, pmid = {37344429}, issn = {1349-7235}, abstract = {A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.}, } @article {pmid37341223, year = {2023}, author = {Saeed, U and Uppal, MR and Uppal, MS and Uppal, R and Khan, AA and Hassan, A and Piracha, ZZ}, title = {Hepatitis C virus associated ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 19-9, iPTH biomarkers, computed tomography and HCV burden of disease during pre COVID-19 era (2018-2019) and post COVID-19 era (2020-2022) in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e271451}, doi = {10.1590/1519-6984.271451}, pmid = {37341223}, issn = {1678-4375}, mesh = {Humans ; Hepacivirus ; Glycated Hemoglobin ; alpha-Fetoproteins ; Pakistan/epidemiology ; *COVID-19 ; *Hepatitis C/epidemiology ; Biomarkers ; Tomography, X-Ray Computed ; Cost of Illness ; }, abstract = {The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.}, } @article {pmid37340705, year = {2023}, author = {Nassar, L and Nakad, S and Abou Zeid, F and Farah, Z and Saheb, G and Mroueh, N and Debs, P and Berjawi, G}, title = {Additional occult cancers identified on staging breast MRI: imaging appearances and pathologic characteristics.}, journal = {Journal of medical radiation sciences}, volume = {}, number = {}, pages = {}, doi = {10.1002/jmrs.694}, pmid = {37340705}, issn = {2051-3909}, abstract = {INTRODUCTION: Breast magnetic resonance imaging (MRI) is increasingly being used for staging of patients with breast cancer due to its high sensitivity in detecting additional cancers (ACs). However, the clinical impact of diagnosing and treating these cancers remains unclear.

METHODS: A retrospective study was undertaken of patients with newly diagnosed breast cancer who underwent staging MRI at The American University of Beirut Medical Centre (AUBMC) between 2012 and 2020. Pathology reports and breast MRI examinations were reviewed. Eighteen breast cancer patients with 19 pathology-proven index cancers (ICs) and 19 pathology-proven MRI-detected ACs were included. Chi-square and Fisher's exact tests for categorical variables and Wilcoxon signed rank test for numerical variables were used to compare ICs to ACs.

RESULTS: The ICs consisted of four ductal carcinoma in situ (DCIS), 13 invasive ductal carcinomas (IDC), of which five with associated DCIS, and two invasive lobular carcinomas, (ILC) of which one with associated DCIS. ACs comprised 12 DCIS, five IDC, two with associated DCIS and two ILC, one with associated DCIS. Interval cancers were more frequently invasive whereas ACs were more frequently in situ (P = 0.021). ACs were more frequently nuclear grade 2 (P = 0.009). There was no statistically significant difference between ICs and ACs in lesion type (P = 0.062), shape (P = 0.073), initial enhancement (P = 1), delayed enhancement (P = 0.732), hormonal receptor profile (P = 0.68) and Ki67 (P = 0.388). Among ACs, ten (53%) were larger than 10 mm of which five (26%) were invasive cancers, and five (26%) were larger than the ICs.

CONCLUSIONS: ACs detected by breast MRI were more likely to be in situ and to show a nuclear grade 2. Although not reaching statistical significance, some ACs tend to be clinically significant by their type, size or nuclear grade. The impact on clinical management remains to be determined.}, } @article {pmid37337121, year = {2023}, author = {Lemmer, IL and Bartelt, A}, title = {Brown fat has a sweet tooth.}, journal = {Nature metabolism}, volume = {5}, number = {7}, pages = {1080-1081}, pmid = {37337121}, issn = {2522-5812}, mesh = {*Adipose Tissue, Brown ; *Taste ; Dietary Fats ; }, } @article {pmid37329252, year = {2023}, author = {Rousseau, S and Feldman, T and Shlomi Polachek, I and Frenkel, TI}, title = {Persistent symptoms of maternal post-traumatic stress following childbirth across the first months postpartum: Associations with perturbations in maternal behavior and infant avoidance of social gaze toward mother.}, journal = {Infancy : the official journal of the International Society on Infant Studies}, volume = {28}, number = {5}, pages = {882-909}, doi = {10.1111/infa.12553}, pmid = {37329252}, issn = {1532-7078}, support = {//Ziama Arkin Infancy Institute at Reichman University, Herzliya, Israel/ ; }, abstract = {Recent literature identifies childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth (PTS-FC). The current study examines whether stable symptoms of PTS-FC during the early postpartum period may impose risk for perturbations in maternal behavior and infant social-engagement with mother, controlling for comorbid postpartum internalizing symptoms. Mother-infant dyads (N = 192) were recruited from the general population, during the third trimester of pregnancy. 49.5% of the mothers were primipara, and 48.4% of the infants were girls. Maternal PTS-FC was assessed at 3-day, 1-month and 4-month postpartum, via self-report and clinician-administered interview. Latent Profile Analysis generated two profiles of symptomology: "Stable-High-PTS-FC" (17.0%), and "Stable-Low-PTS-FC" (83%). Membership in the "Stable-High-PTS-FC" profile associated with perturbed maternal sensitivity, which was in turn significantly associated with infant avoidance of social gaze toward mother (Indirect effect β = -0.15). Results suggest the need for early screening and inform the planning of early preventive interventions.}, } @article {pmid37328333, year = {2023}, author = {Han, LK and Hussain, A and Dodelzon, K and Ginter, PS and Towne, WS and Marti, JL}, title = {Active Surveillance of Atypical Ductal Hyperplasia of the Breast.}, journal = {Clinical breast cancer}, volume = {23}, number = {6}, pages = {649-657}, doi = {10.1016/j.clbc.2023.05.008}, pmid = {37328333}, issn = {1938-0666}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Retrospective Studies ; Prospective Studies ; Watchful Waiting ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; Breast/diagnostic imaging/surgery/pathology ; Biopsy, Large-Core Needle ; Hyperplasia/diagnostic imaging/surgery/pathology ; }, abstract = {BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS.

MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging.

RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%).

CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.}, } @article {pmid37327766, year = {2023}, author = {Adiputra, PAT and Sudarsa, IW and Irawan, H and Saputra, H}, title = {Malignant adnexal tumor of the skin on breast: A case report of apocrine carcinoma.}, journal = {International journal of surgery case reports}, volume = {108}, number = {}, pages = {108383}, pmid = {37327766}, issn = {2210-2612}, abstract = {INTRODUCTION: Malignant adnexal tumors of the skin (MATS) are a group of rare and varied tumors that lack standardized guidelines for their management. Apocrine carcinoma (AC) is a highly uncommon form of breast malignancy, contributing to less than 1 % of all female invasive breast carcinomas. AC has a similar microscopic growth pattern to invasive ductal carcinoma, which can result in early misdiagnosis.

PRESENTATION OF CASE: This report presents a case of a 67-year-old female with a lump in the superior lateral quadrant of her left breast for six years. Surgical therapy was performed with wide excision due to clinical operability, no significant involvement of the axillary lymph nodes, and without metatasis. During the operation, Wide excision of 1-2 cm free margin according to standard and local reconstruction flaps were performed, with berry packing for the identified lymph nodes.

DISCUSSION: The tumor was ER and PR negative, so hormonal treatment would be ineffective, assuming that this is an apocrine carcinoma of the breast. A metastatic work up was already done, and no metastasis was found. A mastectomy would appear to be a viable option.

CONCLUSION: It is important to perform a clinical reevaluation to provide optimal treatment for breast malignancy. Misdiagnosis can occur early. In this case, a surgical procedure involving wide excision was performed, and as of now, the patient has not reported any recurrence.}, } @article {pmid37325006, year = {2023}, author = {Kim, HJ and Lee, JH and Park, YM and Lim, K}, title = {Clustered Microcysts Detected on Breast US in Asymptomatic Women.}, journal = {Journal of the Korean Society of Radiology}, volume = {84}, number = {3}, pages = {676-685}, pmid = {37325006}, issn = {2951-0805}, abstract = {PURPOSE: To investigate the incidence, outcomes, and imaging characteristics of clustered microcysts detected on breast US in asymptomatic women, and suggest appropriate management guidelines.

MATERIALS AND METHODS: We identified and reviewed the lesions recorded as "clustered microcysts" on breast US performed in asymptomatic women between August 2014 and December 2019. The final diagnosis was based on pathology and imaging follow-up results for at least 12 months.

RESULTS: The incidence was 1.5% and 100 patients with 117 lesions were included. Among 117 lesions, 3 (2.6%), 2 (1.7%), and 112 (95.7%) were malignant, high-risk benign, and benign lesions, respectively. The malignant lesions included two cases of ductal carcinoma in situ and one invasive ductal carcinoma. Two of them were assessed as category 4, showing mammographic suspicious microcalcifications and internal vascularity on Doppler US. The remainder was a false negative case and showed echo pattern change on the 12-month follow-up US.

CONCLUSION: The incidence of clustered microcysts on breast US in asymptomatic women was 1.5% and malignancy rate was 2.6% (3 of 117). Knowledge of outcomes and imaging features of benign and malignant clustered microcysts may be helpful for radiologists, thereby aiding categorization and management recommendations.}, } @article {pmid37324999, year = {2023}, author = {Han, YJ and Kim, YM}, title = {Squamous Cell Carcinoma Arising from Epidermal Inclusion Cyst of Breast: Imaging Findings and Literature Review.}, journal = {Journal of the Korean Society of Radiology}, volume = {84}, number = {3}, pages = {776-781}, pmid = {37324999}, issn = {2951-0805}, abstract = {Commonly, epidermal inclusion cysts (EICs) are benign cutaneous lesions that are lined with stratified squamous epithelium and may occur in all body parts, including the breasts. EICs in the breast (EICB) are commonly encountered clinically; it may be under-reported because of their mild and non-specific clinical presentation. Malignant transformation of EICs is extremely rare, occurring 0.011%-0.045%. Presently, we report a rare case of squamous cell carcinoma arising from an EICB of a woman with invasive ductal carcinoma.}, } @article {pmid37324312, year = {2023}, author = {Jain, AK}, title = {Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {2}, pages = {279-287}, pmid = {37324312}, issn = {0975-7651}, abstract = {In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.}, } @article {pmid37322939, year = {2023}, author = {Chaudhury, S and Sau, K and Khan, MA and Shabaz, M}, title = {Deep transfer learning for IDC breast cancer detection using fast AI technique and Sqeezenet architecture.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {20}, number = {6}, pages = {10404-10427}, doi = {10.3934/mbe.2023457}, pmid = {37322939}, issn = {1551-0018}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/diagnostic imaging/pathology ; Neural Networks, Computer ; }, abstract = {One of the most effective approaches for identifying breast cancer is histology, which is the meticulous inspection of tissues under a microscope. The kind of cancer cells, or whether they are cancerous (malignant) or non-cancerous, is typically determined by the type of tissue that is analyzed by the test performed by the technician (benign). The goal of this study was to automate IDC classification within breast cancer histology samples using a transfer learning technique. To improve our outcomes, we combined a Gradient Color Activation Mapping (Grad CAM) and image coloring mechanism with a discriminative fine-tuning methodology employing a one-cycle strategy using FastAI techniques. There have been lots of research studies related to deep transfer learning which use the same mechanism, but this report uses a transfer learning mechanism based on lightweight Squeeze Net architecture, a variant of CNN (Convolution neural network). This strategy demonstrates that fine-tuning on Squeeze Net makes it possible to achieve satisfactory results when transitioning generic features from natural images to medical images.}, } @article {pmid37318317, year = {2023}, author = {Gómez, AM and Bartelt, A}, title = {Endocrine communication of endoplasmic reticulum stress.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {8}, pages = {e2300093}, doi = {10.1002/bies.202300093}, pmid = {37318317}, issn = {1521-1878}, mesh = {*Endoplasmic Reticulum Stress ; *Endoplasmic Reticulum ; Apoptosis ; }, } @article {pmid37307248, year = {2023}, author = {Saito, M and Kato, S and Maeda, T and Komaya, K and Takagi, T and Sekimura, A and Kobayashi, S and Hori, A}, title = {Surgical Management of Breast Cancer Developing Along the Pathway of a Ventriculoperitoneal Shunt: A Case Report.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e939639}, pmid = {37307248}, issn = {1941-5923}, mesh = {Female ; Humans ; Aged, 80 and over ; *Breast Neoplasms ; Ventriculoperitoneal Shunt ; Mastectomy ; Neoplasm Recurrence, Local ; *Hydrocephalus ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND Ventriculoperitoneal shunts are commonly used in neurosurgery for the treatment of hydrocephalus. This case report details an unusual instance where breast cancer developed along the pathway of an existing ventriculoperitoneal shunt. CASE REPORT An 86-year-old woman, who previously underwent ventriculoperitoneal shunt placement for normal-pressure hydrocephalus, visited our hospital upon detecting a mass in her left breast. The physical examination discovered an irregular mass located at the 9 o'clock position of the left breast. Subsequent breast ultrasonography identified a 36 mm mass with indistinct borders, rough margins, and signs of skin infiltration. Invasive ductal carcinoma of a triple-negative subtype was diagnosed through a core-needle biopsy. Contrast-enhanced computed tomography indicated the ventriculoperitoneal shunt's pathway, running from the left ventricle, passing through the center of the breast mass, and leading into the abdominal cavity. Fears of shunt occlusion and potential infection due to the untreated breast cancer prompted surgical intervention after consultation with the neurosurgeon. The surgery involved rerouting the ventriculoperitoneal shunt from the left thoracoabdomen to the right, performing a left mastectomy, and removing the fistula in the abdominal wall to minimize the risk of cancer recurrence along the shunt pathway. Postoperative histopathological examination confirmed the initial diagnosis of invasive ductal carcinoma of a triple-negative subtype, with no malignancy detected in the removed abdominal wall fistula. CONCLUSIONS Taking into account prior cases of cancer metastasizing distantly due to ventriculoperitoneal shunts, our case emphasizes the necessity to consider additional preventative measures against cancer seeding. This approach is particularly significant when treating breast cancer that arises along the pathway of a ventriculoperitoneal shunt, apart from performing conventional breast cancer surgery.}, } @article {pmid37305344, year = {2023}, author = {Safari, A and Hamza, S and Paton, D}, title = {A rare case: synchronous ipsilateral breast implant-associated anaplastic large cell lymphoma and invasive ductal carcinoma.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {6}, pages = {rjad338}, pmid = {37305344}, issn = {2042-8812}, abstract = {A 78-year-old female with a history of cosmetic breast implants presented with unilateral breast enlargement and was subsequently diagnosed with stage IA breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as well as stage IB ipsilateral synchronous invasive ductal carcinoma (IDC). Her assessment included bilateral breast ultrasounds,mammograms and MRIs with right-sided fine needle aspiration of peri-implant fluid, core biopsy of right breast mass and a whole-body positron emission tomography scan. She was surgically treated with bilateral capsulectomy, implant removal and mastectomy. No adjuvant treatment was required for the BIA-ALCL. The IDC required adjuvant chemotherapy, radiotherapy and endocrine therapy. This rare case highlights the paramount importance of thorough evaluation of suspected BIA-ALCL patients for synchronous breast pathologies. We conclude with a concise summary of the salient points on evaluation and management of BIA-ALCL for surgeons.}, } @article {pmid37302209, year = {2023}, author = {Birnbaum, GE}, title = {The enticement of feeling understood, validated, and cared for: How does perceiving a partner as responsive affect the sexual arena?.}, journal = {Current opinion in psychology}, volume = {52}, number = {}, pages = {101594}, doi = {10.1016/j.copsyc.2023.101594}, pmid = {37302209}, issn = {2352-2518}, mesh = {Humans ; *Interpersonal Relations ; *Sexual Behavior ; Sexual Partners ; Emotions ; }, abstract = {Partners' behaviors outside the bedroom may spill over into the bedroom. One such behavior is responsiveness, as it creates a relationship ambiance conducive to the development of intimacy. In this article, I review research demonstrating how perceiving partners as responsive outside the bedroom affects the quality of sexual interactions, highlighting changes in the contextual meaning of partner responsiveness across individuals and relationship stages. I then provide an overview of the costs and benefits of responsiveness within the bedroom. I conclude by suggesting directions for future research on the potential of partner responsiveness for fostering a relationship environment that inoculates against alternative partners as well as for designing social robots and virtual mates for those in need of a surrogate partner.}, } @article {pmid37301537, year = {2023}, author = {Wu, K and Li, W and Liu, H and Niu, C and Shi, Q and Zhang, J and Gao, G and Sun, H and Liu, F and Fu, L}, title = {Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.}, journal = {The American journal of pathology}, volume = {193}, number = {9}, pages = {1267-1283}, doi = {10.1016/j.ajpath.2023.05.010}, pmid = {37301537}, issn = {1525-2191}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Disease-Free Survival ; *Carcinoma, Papillary/pathology ; *Breast Neoplasms/metabolism ; Metabolome ; Methyltransferases/metabolism ; Prognosis ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; Repressor Proteins/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.}, } @article {pmid37300453, year = {2023}, author = {Cicek, SK and Simsek, B and Gundogdu, C}, title = {Right Common Femoral Vein Invasion: A Unique Case of Inguinal Ectopic Breast Cancer.}, journal = {Vascular and endovascular surgery}, volume = {57}, number = {8}, pages = {914-918}, doi = {10.1177/15385744231183489}, pmid = {37300453}, issn = {1938-9116}, mesh = {Animals ; Cattle ; Humans ; Female ; *Breast Neoplasms/diagnostic imaging/therapy ; Breast/pathology ; Groin ; Femoral Vein/diagnostic imaging/surgery/pathology ; Treatment Outcome ; *Choristoma/diagnosis/pathology ; }, abstract = {OBJECTIVES: Ectopic breast cancer may present anywhere in the milk line, from the axilla to the groin which is extremely rare in the inguinal region. Despite morphologic differences, ectopic breast tissue presents characteristics related to orthotopic breast tissue in terms of function and pathologic degeneration. The case report describes the treatment of a unique ectopic breast carcinoma which was located in the inguinal region with a common femoral vein invasion.

METHODS: We present a unique case of an ectopic breast carcinoma presenting in an unusual anatomic location along the milk line. The study was approved by the local Ethics Committee (protocol no: 12.01.2023-2023/02) Informed consent was obtained from the patient.

RESULTS: The patient is surgically treated and supplemented with neoadjuvant chemotherapy,radiotherapy and endocrine therapy. Histopathological examination revealed the diagnosis of invasive ductal carcinoma. The right common femoral vein was reconstructed with bovine pericardial patch after totally removal of the mass.

CONCLUSIONS: This report alerts the reader to be cognizant of the unusual location of an ectopic breast cancer which was detected in the inguinal region with a common femoral vein invasion and discusses the treatment, suggesting novel therapeutic advice that could bring considerable clinical advantages. A multidisciplinary approach should be warranted in such cases to confirm a complete remission.}, } @article {pmid37296828, year = {2023}, author = {Kumaraswamy, E and Kumar, S and Sharma, M}, title = {An Invasive Ductal Carcinomas Breast Cancer Grade Classification Using an Ensemble of Convolutional Neural Networks.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {37296828}, issn = {2075-4418}, abstract = {Invasive Ductal Carcinoma Breast Cancer (IDC-BC) is the most common type of cancer and its asymptomatic nature has led to an increased mortality rate globally. Advancements in artificial intelligence and machine learning have revolutionized the medical field with the development of AI-enabled computer-aided diagnosis (CAD) systems, which help in determining diseases at an early stage. CAD systems assist pathologists in their decision-making process to produce more reliable outcomes in order to treat patients well. In this work, the potential of pre-trained convolutional neural networks (CNNs) (i.e., EfficientNetV2L, ResNet152V2, DenseNet201), singly or as an ensemble, was thoroughly explored. The performances of these models were evaluated for IDC-BC grade classification using the DataBiox dataset. Data augmentation was used to avoid the issues of data scarcity and data imbalances. The performance of the best model was compared to three different balanced datasets of Databiox (i.e., 1200, 1400, and 1600 images) to determine the implications of this data augmentation. Furthermore, the effects of the number of epochs were analysed to ensure the coherency of the most optimal model. The experimental results analysis revealed that the proposed ensemble model outperformed the existing state-of-the-art techniques in relation to classifying the IDC-BC grades of the Databiox dataset. The proposed ensemble model of the CNNs achieved a 94% classification accuracy and attained a significant area under the ROC curves for grades 1, 2, and 3, i.e., 96%, 94%, and 96%, respectively.}, } @article {pmid37293082, year = {2023}, author = {Subudhi, AK and Green, JL and Satyam, R and Lenz, T and Salunke, RP and Shuaib, M and Isaioglou, I and Abel, S and Gupta, M and Esau, L and Mourier, T and Nugmanova, R and Mfarrej, S and Sivapurkar, R and Stead, Z and Rached, FB and Otswal, Y and Sougrat, R and Dada, A and Kadamany, AF and Fischle, W and Merzaban, J and Knuepfer, E and Ferguson, DJP and Gupta, I and Le Roch, KG and Holder, AA and Pain, A}, title = {PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37293082}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI136511/AI/NIAID NIH HHS/United States ; R21 AI142506/AI/NIAID NIH HHS/United States ; }, abstract = {Malaria pathogenicity results from the parasite's ability to invade, multiply within and then egress from the host red blood cell (RBC). Infected RBCs are remodeled, expressing antigenic variant proteins (such as PfEMP1, coded by the var gene family) for immune evasion and survival. These processes require the concerted actions of many proteins, but the molecular regulation is poorly understood. We have characterized an essential Plasmodium specific Apicomplexan AP2 (ApiAP2) transcription factor in Plasmodium falciparum (PfAP2-MRP; Master Regulator of Pathogenesis) during the intraerythrocytic developmental cycle (IDC). An inducible gene knockout approach showed that PfAP2-MRP is essential for development during the trophozoite stage, and critical for var gene regulation, merozoite development and parasite egress. ChIP-seq experiments performed at 16 hour post invasion (h.p.i.) and 40 h.p.i. matching the two peaks of PfAP2-MRP expression, demonstrate binding of PfAP2-MRP to the promoters of genes controlling trophozoite development and host cell remodeling at 16 h.p.i. and antigenic variation and pathogenicity at 40 h.p.i. Using single-cell RNA-seq and fluorescence-activated cell sorting, we show de-repression of most var genes in Δpfap2-mrp parasites that express multiple PfEMP1 proteins on the surface of infected RBCs. In addition, the Δpfap2-mrp parasites overexpress several early gametocyte marker genes at both 16 and 40 h.p.i., indicating a regulatory role in the sexual stage conversion. Using the Chromosomes Conformation Capture experiment (Hi-C), we demonstrate that deletion of PfAP2-MRP results in significant reduction of both intra-chromosomal and inter-chromosomal interactions in heterochromatin clusters. We conclude that PfAP2-MRP is a vital upstream transcriptional regulator controlling essential processes in two distinct developmental stages during the IDC that include parasite growth, chromatin structure and var gene expression.}, } @article {pmid37292245, year = {2023}, author = {Thu Huong, N and Hue, TT and Duy Hung, N and Minh Duc, N}, title = {Ductal carcinoma in situ arises from microglandular adenosis and atypical microglandular adenosis in a young woman.}, journal = {Journal of clinical imaging science}, volume = {13}, number = {}, pages = {15}, pmid = {37292245}, issn = {2156-7514}, abstract = {Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are intensely rare and distinctive forms of adenosis of the breast, usually occurring in middle-aged women. Carcinoma arising in MGA is an extremely rare subtype of breast carcinoma, and most reported cases are of invasive carcinoma. Ultrasound and magnetic resonance imaging are accurate imaging modalities for diagnosing these abnormalities. Our goal in this article was to report a rare instance of ductal carcinoma in situ (DCIS) arising from MGA and AMGA in a very young Vietnamese woman who presented with a palpable mass in her right breast for 1 month. During clinical examination and imaging, suspected lesions were found and categorized as BI-RADS 4a. The final histopathological findings confirmed DCIS arising from MGA/AMGA. In this patient, the disease was detected and managed early when the lesion was localized in the duct and there were no signs of invasive ductal carcinoma.}, } @article {pmid37290673, year = {2023}, author = {Nieborak, A and Lukauskas, S and Capellades, J and Heyn, P and Santos, GS and Motzler, K and Zeigerer, A and Bester, R and Protzer, U and Schelter, F and Wagner, M and Carell, T and Hruscha, A and Schmid, B and Yanes, O and Schneider, R}, title = {Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.}, journal = {Molecular metabolism}, volume = {74}, number = {}, pages = {101748}, pmid = {37290673}, issn = {2212-8778}, mesh = {Animals ; *Pyruvate Kinase/genetics ; Reactive Oxygen Species ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; *Neoplasms/genetics/metabolism ; Thioredoxins/chemistry/metabolism ; }, abstract = {OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.

METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.

RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.

CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.}, } @article {pmid37284541, year = {2023}, author = {De Matos, CC and Guignard, B and Castro, FS and Guimard, A}, title = {Effects of paddles and fins on front crawl kinematics, arm stroke efficiency, coordination, and estimated energy cost.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1174090}, pmid = {37284541}, issn = {1664-042X}, abstract = {Paddles and fins are used in swimmers training with different objectives (e.g., increase propulsive areas of hands and feet, improve the feeling of water flow). These artificial modifications of the stroke might be viewed as external constraints of the stroke task, both will either disturb or facilitate swimming modalities, so the coaches should manipulate its use to extract benefits for performance. This study seeks to investigate the precise effects of wearing either paddles (PAD) or fins (FINS) vs. a no-equipment (NE) trial in three all-out front crawl exercises on swimmer kinematics, arm stroke efficiency (ηp), upper-limbs coordination patterns (Index of Coordination, IdC), and estimated energy cost (C). Eleven regional to national-level male swimmers participated in the study (age: 25.8 ± 5.5 years, body mass: 75.2 ± 5.5 kg, height: 177 ± 6.5 cm) and were recorded from both sides of the swimming pool to collect all variables. Repeated measures ANOVA and Bonferroni post hoc were used to compare the variables. Effects sizes were calculated. Time to cover the distance and velocity were higher in FINS swimming, with larger values of stroke length (SL) and lower kick amplitude in comparison to the other trials (PAD and NE). The use of FINS also modified the stroke phases durations by presenting significant lower propulsion time during the stroke in comparison to PAD or NE. Values of IdC were lower (IdC < -1%, so catch-up pattern of coordination) for FINS in comparison to NE. In terms of ηp, using PAD or FINS demonstrate higher arm stroke efficiency than swimming without equipment. Finally, C was significantly higher in FINS swimming in comparison to NE and PAD. From the present results, it should be noted that the use of equipment such as fins deeply modify the structure of the swimming stroke (from the performance-related parameters through the kinematics of both upper and lower limbs to the stroke efficiency and coordination pattern). So, using equipment should be appropriately scaled by the coaches to the objectives of the training session in swimming, and in emergent sports such as "SwimRun", paddles and fins must be viewed as tools to achieve higher velocities to cover a given distance.}, } @article {pmid37283256, year = {2023}, author = {Bukamal, Z and AlRayes, A}, title = {Prevalence of BRCA1 and BRCA2 Mutations Among High-risk Bahraini Patients with Breast Cancer.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {42}, pages = {22-25}, pmid = {37283256}, issn = {2078-2101}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/epidemiology/genetics/diagnosis ; Bahrain/epidemiology ; Retrospective Studies ; Prevalence ; Mutation ; *Carcinoma, Ductal ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; }, abstract = {OBJECTIVE: The purpose is to study the prevalence of BRCA1 and BRCA2 mutations in high-risk Bahraini patients diagnosed with breast cancer, its relation to family history, and to determine the clinicopathologic features of breast cancer associated with these genetic mutations, over a period of 7 years.

BACKGROUND: Breast cancer is the most common type of cancer occurring in women and the second most common type generally. Approximately 12% of women worldwide will develop carcinoma of the breast sometime during their life. Additionally, 72% of women with an inherited BRCA1 mutation and 69% of those with a mutated BRCA2 will develop breast cancer by 80 years of age. The incidence of breast cancer in Bahraini women have increased over the last decade. Still, the data on BRCA1 & BRCA2 mutations in relation to breast cancer patients is limited in the Arab region, not omitting Bahrain as a country with deficient BRCA prevalence data.

METHODS: This retrospective study was carried out in Salmaniya Medical Complex, Bahrain, to determine the prevalence of BRCA1 and BRCA2 mutations and to observe the breast cancer's histopathologic features that are associated with these mutations.

RESULTS: 271 patients underwent the BRCA gene testing between 2013 and 2019. Out of 271 patients, 35 were excluded. Out of the 236 breast cancer patients, 219 (93%) did not have the mutation. The BRCA gene was carried by a total of 17 (7%) patients; 13 (5%) BRCA1 and 4 (2%) BRCA2. Thirteen BRCA carrier patients had invasive ductal carcinoma (IDC) (76%), 2 had ductal carcinoma in situ (DCIS) (12%), while 2 patients' histopathology was not available. Molecular subtypes showed 4 triple negative basal sub-type (TNBC), 10 positive ER and PR hormonal status, 1 positive HER-2, while 2 patients' hormonal receptor status was not available. Two BRCA1 carriers had both breast and ovarian cancers. A total of 5 (2%) breast cancer male patients were among the tested population, out of which, 1 (0.4% of the total and 20% of the male patients) was a BRCA2 carrier. Out of the 236 patients, 76 (32%) were younger than 40 years of age at the time of diagnosis. Then again, out of the 17 BRCA carrier patients, 7 (41%) were younger than 40 years.

CONCLUSION: The prevalence of BRCA mutation in high risk Bahraini breast cancer patients is 7%. Among those patients, BRCA1 mutation is the most prevalent (5%) and invasive ductal carcinoma (IDC) is the most common histopathological subtype. However, there was not enough data to conclude the most prevalent molecular subtype of breast cancer in BRCA carriers due to deficiency of overseas pathology reports for patients operated outside Bahrain. When developing treatment plans for younger patients with breast cancer, inherited syndromes and precisely BRCA mutations need to be considered. Bahrain is implementing genetic testing for breast cancer patients ≤ 50 years of age since 2018, according to NCCN guidelines. We will continue to build our database to better characterize breast cancer subtypes and determine their hereditary pattern for identification of high risk families in Bahrain and for future development of more specific therapeutic approaches.

KEY WORDS: Breast cancer, BRCA1, BRCA2, BRCA mutation, Bahrain, Arab region.}, } @article {pmid37276118, year = {2023}, author = {Chen, CB and Wang, Y and Fu, X and Yang, H}, title = {Recurrence Network Analysis of Histopathological Images for the Detection of Invasive Ductal Carcinoma in Breast Cancer.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TCBB.2023.3282798}, pmid = {37276118}, issn = {1557-9964}, abstract = {The histopathological image analysis is one of the most crucial diagnostic procedures to identify Invasive ductal carcinoma (IDC) in breast cancers. However, this diagnosis process is currently time-consuming and heavily dependent on human expertise. Prior research has shown that different degrees of tumors present various microstructures in the histopathological images. However, very little has been done to utilize spatial recurrence features of microstructures for identifying IDC. This paper presents a novel recurrence analysis methodology for automatic image-guided IDC detection. We first utilize wavelet decomposition to delineate the subtle information in the images. Then, we model the patches with a weighted recurrence network approach to characterize the recurrence patterns of the histopathological images. Finally, we develop automated IDC detection models leveraging machine learning methods with spatial recurrence features extracted. The developed recurrence analysis models successfully characterize the complex microstructures of histopathological images and achieve the IDC detection performances of at least AUC = 0.96. This research developed a spatial recurrence analysis methodology to effectively identify IDC regions in histopathological images for BC. It shows a high potential to assist physicians in the decision-making process. The proposed methodology can further be applicable to image processing for other medical or biological applications.}, } @article {pmid37274780, year = {2023}, author = {Xiang, J and Gong, W and Liu, J and Zhang, H and Li, M and Wang, R and Lv, Y and Sun, P}, title = {Identification of DLL3-related genes affecting the prognosis of patients with colon adenocarcinoma.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1098190}, pmid = {37274780}, issn = {1664-8021}, abstract = {Background: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.}, } @article {pmid37270436, year = {2023}, author = {Jiao, Y and Guo, X and Wu, H and Lv, Q}, title = {Surgery on Metastatic Foci is a Better Strategy for Stage IV Breast Cancer Patients with only Nonregional Lymph Node Metastasis.}, journal = {Advances in therapy}, volume = {40}, number = {7}, pages = {3247-3262}, pmid = {37270436}, issn = {1865-8652}, support = {ZYJC18018//West China Hospital, Sichuan University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy ; Lymphatic Metastasis/pathology ; Lymph Nodes/surgery/pathology ; Prognosis ; Lymph Node Excision ; }, abstract = {INTRODUCTION: Our study aims to explore whether breast cancer patients with non-regional lymph node (NRLN) metastasis benefit from surgery on distant nodes, and to determine the influencing factors affecting the prognosis of this type of patient.

METHODS: Information of invasive ductal carcinoma (IDC) patients from 2004 to 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed by statistical methods, including multivariate Cox regression model, chi-squared test, propensity score matching (PSM), Kaplan-Meier plot, and log-rank test.

RESULTS: A total of 4236 M1 patients met the designated criteria. Among 847 patients with only NRLN metastasis who have detailed information, only 114 patients received surgery on metastatic distant lymph nodes. The Kaplan-Meier plot for overall survival (OS) showed that the prognosis of NRLN metastatic patients was superior to visceral metastasis (P < 0.0001) but similar to supraclavicular metastasis (P = 0.33). In addition, NRLN metastatic patients who underwent surgery on the NRLNs were found to have superior prognoses in terms of both OS (P = 0.041) and cancer-specific survival (P = 0.034) compared with those who did not undergo NRLN surgery. We have also demonstrated that NRLN metastatic patients who have received radiotherapy plus chemotherapy for primary tumors gain superior survival compared with those who only received chemotherapy apart from NRLN surgery.

CONCLUSION: Surgery on NRLN and radiotherapy for the primary tumor improved the prognosis of NRLN metastatic patients. Thus, the classification of NRLN, especially contralateral axillary lymph node metastasis (CAM), into the M1 breast cancer stage should be reconsidered. Different locoregional treatment strategies for metastatic foci should be recommended for patients with only NRLN and patients with visceral metastasis.}, } @article {pmid37268513, year = {2023}, author = {Bernardino, R and Sayyid, RK and Al-Daqqaq, Z and Tiwari, R and Cockburn, J and Vijayakanthan, S and Qaoud, Y and Berjaoui, MB and Metser, U and Berlin, A and van der Kwast, T and Fleshner, NE}, title = {Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2023.05.005}, pmid = {37268513}, issn = {2405-4569}, abstract = {BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns.

OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread.

A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing [18]F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre.

Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses.

RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004).

CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies.

PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.}, } @article {pmid37266479, year = {2023}, author = {Al-Zadjali, Y and Al-Rashdi, A and Al-Husaini, S and Al-Badi, S and Al-Badi, H and Arafa, M}, title = {Clinicopathological Study of Breast Carcinoma Patients with Equivocal HER2 Immunohistochemical Status: Five-Year Experience from a Tertiary Care Center.}, journal = {Maedica}, volume = {18}, number = {1}, pages = {27-34}, pmid = {37266479}, issn = {1841-9038}, abstract = {Background and objectives: Assessment of HER2 gene status has central role in the management of breast cancer patients. For determining HER2 status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most commonly used tests. Immunohistochemistry scores of 3+ and 1+ were considered as HER2 positive and negative, respectively. On the other hand, HER2 equivocal cases need further confirmation by FISH test assessment. This study aimed to identify the clinicopathological characteristics of patients with HER2 equivocal tumors served by Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, with emphasis on treatment plans and disease outcome. Methods: This was a retrospective cross-sectional study, which involved all breast cancer female patients who were referred to SQUH from 2016 to 2020. It included a total of 108 patients who were diagnosed with HER2 (2+) breast cancer. Patients' data were analyzed in relation to the subsequent FISH status. Results: During the study period, data from 108 females with HER2 2+ were collected; among them, 22 (20%) were FISH positive, 64 (59%) FISH negative, 17 (16%) FISH borderline and five (5%) with no results. Regarding patients' characteristics, 91.2% of all subjects had invasive ductal carcinoma, 93.2% expressed estrogen receptors and 77.6% progesterone receptor. Age, postmenopausal histopathology, tumor grade, TNM staging, ER, PR, Ki67, LVSI, NLR, treatment and follow-up did not show significant association with different FISH results. Conclusions: The majority of HER2 equivocal breast cancer cases were FISH negative. In trastuzumab chemotherapy, an association between different FISH results was expected.}, } @article {pmid37266061, year = {2023}, author = {Jogie, JA and Maharaj, A and Mahase, T and Bhagwandeen, S and Ramcharan, L and Mohammed, R and Ramdass, J and Deyalsingh, V}, title = {A Preliminary Analysis of Ki-67 Expression in Breast Cancer in the Caribbean.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e38351}, pmid = {37266061}, issn = {2168-8184}, abstract = {OBJECTIVE: There has been a void of data regarding Ki-67 expression in breast cancer in the Caribbean. Ki-67 is a widely used marker to determine the grade and prognosis of breast cancer. Ki-67 has been shown to be a valuable tool in predicting the response to chemotherapy and hormonal therapy in breast cancer patients. The objective of this preliminary study aims to describe the Ki-67 (Ki) status in this population and its correlations with other parameters in breast cancer histology. This study also aims to lay the groundwork for Ki-67 analysis in this population so that future studies may better describe it.

METHOD: The methodology involved gathering data from histology reports for all breast cancer-related biopsies from the 1st of January 2018 to the 12th of July 2021. This data was retrospectively analyzed.

RESULTS: Twenty-three Ki-67 cases were obtained, 19 of which had Ki expression >10%. This >10% group was mostly staged from T1c up (one T1, three T1c cases, two T2 cases, four T3 cases while nine were not T staged). Two were N2/M1 while 9 were N0 and two were M0, the rest were not staged. The mean age was 65.6 years with a range of 54 and a standard deviation of 12.5. Lymphovascular invasion was confirmed in four cases and suspected in three. Axillary lymph node dissection (ALND) yielded >10 nodes involved in two cases while <5 nodes in the remaining. The most common receptor status was hormone positive/ human epidermal growth factor receptor-2 (HER) negative (eight). Invasive Ductal Carcinoma (IDC) occurred in 10 cases while intermediate grade was in 14 cases. The Ki 6-10 % group consisted of two cases, one staged at T1aN0Mx while the other T2NxMx. Lymphovascular invasion was suspected in one. The average age was 67.5 years. ALND yielded less than five nodes in one case and 5-10 nodes in the other. Grades were high and intermediate. Histology was invasive ductal carcinoma/ductal carcinoma in situ (IDC/DCIS), and ductal carcinoma in situ (DCIS) respectively. The Ki <6% group comprised two cases, staged at T1NxMx and T3N2M1. Lymphovascular invasion was absent in both. The mean age was 58.5 years. ALND yielded >10 nodes in one case and <5 in the other. Grades were high and intermediate. Histology was IDC/DCIS in both. There were no sentinel nodes involved in all but two cases belonging to the Ki >10% group.

CONCLUSION: This preliminary study was the first to describe the Ki-67 marker in the Caribbean population. The vast majority of this population has a Ki-67 level of>10%. Higher Ki-67 expression is associated with larger tumors, lymphovascular invasion, metastases, and higher tumor grades. There is a need for consistent Ki-67 reporting in histology samples before follow-up studies are conducted.}, } @article {pmid37260825, year = {2023}, author = {Boșoteanu, LA and Așchie, M and Orǎșanu, CI and Boșoteanu, M}, title = {HER2 Negative Mammary Paget's Disease or In Situ Melanoma? A Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2023}, number = {}, pages = {1101130}, pmid = {37260825}, issn = {2090-6781}, abstract = {Mammary Paget's disease (MPD) is a rare histological condition, accounting for 1-4% of female breast cancers, which may appear either independently (1.4-13% of the cases), or in association with an in situ or invasive ductal carcinoma (approximately 90% of the cases). The purpose of this article is to highlight the histopathological challenges related to the microscopical polymorphism of this disease and the utmost importance of immunohistochemistry in the thorough process of Paget's disease differential diagnosis. Moreover, the primary objective of this review of literature was to corroborate the existing data concerning the potential peculiar immunohistochemical profile that mammary Paget's disease might express. We report the case of a 44-year-old female patient, histopathologically diagnosed with HER2-negative MPD accompanying an invasive mammary carcinoma. The histopathological and immunohistochemical approach is derived from the exigency of excluding the possibility of synchronous tumors-a mammary invasive carcinoma, accompanied by another component with MPD phenotypic mimicry. The unexpected negative HER2 reaction is conducted to a primary focus on excluding a malignant melanoma in situ. The absence of MelanA and S100 immunoexpression and lack of pigmentation and clinical aspects infirmed it. Bowen's disease was invalidated by its rare presentation in the breast cutaneous tissue and the absence of individual risk factors suggestive of an existing immunosuppressive status. In the case of similar morphoimmunohistochemical aspects, significant expression of Ki-67 signals MPD, an immunoreactivity that helped distinguish the cellular population from Toker cells. The great similarity of MPD with other benign and malignant cutaneous tumors might determine delay or misdiagnosis. Thus, the utmost importance of immunohistochemistry is reflected in its prognostic significance and geared towards extending the therapeutic arsenal.}, } @article {pmid37256575, year = {2023}, author = {Lobato, P and Moriano, JA and Laguía, A and Molero, F and Mikulincer, M}, title = {Security providing leadership and work stress in Spanish Air Force.}, journal = {Military psychology : the official journal of the Division of Military Psychology, American Psychological Association}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/08995605.2023.2218785}, pmid = {37256575}, issn = {1532-7876}, abstract = {Leadership plays a key role in the well-being of military personnel, either contributing to health improvement or, conversely, becoming a source of stress. In the present study we propose that security providing leadership can reduce work stress in the military context. Furthermore, we suggest that security-providing leaders exert their positive influence on work stress by creating a psychological safety climate and preventing organizational dehumanization. A sample of 204 members (72.5% men) of the Spanish Air Force volunteered to participate in this empirical study and completed an online questionnaire and both the direct and indirect structural equation models were analyzed. Results show a negative relationship between security providing leadership and work stress. Additionally, organizational dehumanization and psychological safety climate act as mediators in this relationship. These results support this novel approach to leadership in the military context. They also offer new ways to create better organizational environments. By treating their subordinates in a personalized manner and supporting them, security-providing leaders can improve employees' perceptions of psychological safety climate and combat feelings of organizational dehumanization, which, in turn, can reduce work stress.}, } @article {pmid37253791, year = {2023}, author = {Sorin, V and Klang, E and Sklair-Levy, M and Cohen, I and Zippel, DB and Balint Lahat, N and Konen, E and Barash, Y}, title = {Large language model (ChatGPT) as a support tool for breast tumor board.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {44}, pmid = {37253791}, issn = {2374-4677}, abstract = {Large language models (LLM) such as ChatGPT have gained public and scientific attention. The aim of this study is to evaluate ChatGPT as a support tool for breast tumor board decisions making. We inserted into ChatGPT-3.5 clinical information of ten consecutive patients presented in a breast tumor board in our institution. We asked the chatbot to recommend management. The results generated by ChatGPT were compared to the final recommendations of the tumor board. They were also graded independently by two senior radiologists. Grading scores were between 1-5 (1 = completely disagree, 5 = completely agree), and in three different categories: summarization, recommendation, and explanation. The mean age was 49.4, 8/10 (80%) of patients had invasive ductal carcinoma, one patient (1/10, 10%) had a ductal carcinoma in-situ and one patient (1/10, 10%) had a phyllodes tumor with atypia. In seven out of ten cases (70%), ChatGPT's recommendations were similar to the tumor board's decisions. Mean scores while grading the chatbot's summarization, recommendation and explanation by the first reviewer were 3.7, 4.3, and 4.6 respectively. Mean values for the second reviewer were 4.3, 4.0, and 4.3, respectively. In this proof-of-concept study, we present initial results on the use of an LLM as a decision support tool in a breast tumor board. Given the significant advancements, it is warranted for clinicians to be familiar with the potential benefits and harms of the technology.}, } @article {pmid37251671, year = {2023}, author = {Kender, Z and von Rauchhaupt, E and Schwarz, D and Tsilingiris, D and Schimpfle, L and Bartl, H and Longo, VD and Bendszus, M and Kopf, S and Herzig, S and Heiland, S and Szendroedi, J and Sulaj, A}, title = {Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1143799}, pmid = {37251671}, issn = {1664-2392}, mesh = {Humans ; Action Potentials ; *Diabetes Mellitus, Type 2/complications/pathology ; *Diabetic Neuropathies/diagnosis ; Fasting ; Pain ; }, abstract = {BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).

STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.

RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.

CONCLUSIONS: Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.

CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.}, } @article {pmid37248945, year = {2023}, author = {Ma, J}, title = {Application value of digital tungsten-molybdenum dual target three-dimensional positioning indwelling guide wire excision biopsy in diagnosis of breast microcalcification.}, journal = {Journal of X-ray science and technology}, volume = {31}, number = {4}, pages = {853-864}, doi = {10.3233/XST-230039}, pmid = {37248945}, issn = {1095-9114}, mesh = {Humans ; Female ; Molybdenum ; Tungsten ; Retrospective Studies ; Hyperplasia/pathology ; *Breast Diseases/diagnostic imaging/surgery/pathology ; *Breast Neoplasms/diagnostic imaging/surgery ; Breast/diagnostic imaging/surgery/pathology ; Biopsy/methods ; Mammography/methods ; *Calcinosis/diagnostic imaging/surgery/pathology ; }, abstract = {OBJECTIVE: To explore the application value of digital tungsten-molybdenum double target three-dimensional positioning indwelling guide wire and guided surgical resection biopsy in the diagnosis of breast microcalcification.

METHODS: A retrospective analysis of 168 patients with negative clinical palpation and molybdenum target X-ray examination found breast abnormalities were equally divided into two groups according to different surgical positioning methods. The control and observation group underwent gross positioning biopsy and digital tungsten-molybdenum dual-target three-dimensional positioning indwelling guide wire to guide surgical resection biopsy, respectively. The results of molybdenum target X-ray examination and the success rate of one-time complete resection of the lesions were compared between the two groups, and the corresponding relationship between the pathological diagnosis results of the lesions after surgical resection and the performance of mammography in the observation group was compared.

RESULTS: There was no significant difference in age and molybdenum target X-ray examination results between the two groups (P > 0.05). General information is comparable; the success rate of one-time complete resection of lesions in the observation group was significantly higher than that in the control group (95.2% vs 78.6%, P = 0.024). There were 34 cases of malignant lesions in the observation group, accounting for 40.5% (34/84), including 11 cases of invasive ductal carcinoma (64.7%), 50 cases of benign lesions, accounting for 59.5% (50/84), including 16 cases of breast lobular hyperplasia (32%), 18 cases of breast cystic hyperplasia (36%).

CONCLUSION: In diagnosis of breast microcalcifications, surgical resection biopsy guided using digital tungsten-molybdenum double target three-dimensional positioning indwelling guide wire achieves high success rate and has advantages of high safety and accurate diagnosis. Thus, it has potential to play a greater role in early diagnosis of breast cancer and is worthy of clinical application.}, } @article {pmid37246414, year = {2023}, author = {Lee, J and Park, S and Jung, HA and Lee, SH and Seo, S and Kim, SB and Kim, JW and Lee, KW and Kang, EJ and Kim, JW and Choi, YJ and Shim, BY and An, HJ and Park, LC and Shin, SH and Kim, JJ and Oh, SY and Kim, MK and Ahn, MJ}, title = {A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.}, journal = {Cancer}, volume = {129}, number = {19}, pages = {2966-2974}, doi = {10.1002/cncr.34892}, pmid = {37246414}, issn = {1097-0142}, mesh = {Humans ; Female ; Docetaxel/therapeutic use ; Micelles ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; *Carcinoma, Ductal ; Salivary Glands/metabolism ; *Breast Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.

METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m[2]) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR).

RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.

CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.

PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.}, } @article {pmid37235845, year = {2023}, author = {Dayes, IS and Metser, U and Hodgson, N and Parpia, S and Eisen, AF and George, R and Blanchette, P and Cil, TD and Arnaout, A and Chan, A and Levine, MN}, title = {Impact of [18]F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {23}, pages = {3909-3916}, doi = {10.1200/JCO.23.00249}, pmid = {37235845}, issn = {1527-7755}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography/methods ; *Breast Neoplasms/diagnostic imaging/therapy/pathology ; Radiopharmaceuticals ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Positron-Emission Tomography/methods ; }, abstract = {PURPOSE: Patients with locally advanced breast cancer (LABC) typically undergo staging tests at presentation. If staging does not detect metastases, treatment consists of curative intent combined modality therapy (neoadjuvant chemotherapy, surgery, and regional radiation). Positron emission tomography-computed tomography (PET-CT) may detect more asymptomatic distant metastases, but the evidence is based on uncontrolled studies.

METHODS: For inclusion, patients had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1). Consenting patients from six regional cancer centers in Ontario were randomly assigned to [18]F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of the chest/abdomen and pelvis). The primary end point was upstaging to stage IV. A key secondary outcome was receiving curative intent combined modality therapy (ClinicalTrials.gov identifier: NCT02751710).

RESULTS: Between December 2016 and April 2022, 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging. Forty-three (23%) PET-CT patients were upstaged to stage IV compared with 21 (11%) conventional staged patients (absolute difference, 12.3% [95% CI, 3.9 to 19.9]; P = .002). Consequently, treatment was changed in 35 (81.3%) of 43 upstaged PET-CT patients and 20 (95.2%) of the 21 upstaged conventional patients. Subsequently, 149 (81%) patients in the PET-CT group received combined modality treatment versus 165 (89.2%) patients in the conventional staging group (absolute difference, 8.2% [95% CI, 0.1 to 15.4]; P = .03).

CONCLUSION: In patients with LABC, PET-CT detected more distant metastases than conventional staging, and fewer PET-CT patients received combined modality therapy. Our randomized trial demonstrates the utility of the PET-CT staging strategy.}, } @article {pmid37233606, year = {2023}, author = {Belachew, EB and Desta, AF and Deneke, DB and Fenta, BD and Alem, AT and Abafogi, AK and Lukas, FY and Bezabih, M and Sewasew, DT and Kantelhardt, EJ and Tessema, TS and Howe, R}, title = {Clinicopathological Features of Invasive Breast Cancer: A Five-Year Retrospective Study in Southern and South-Western Ethiopia.}, journal = {Medicines (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {}, pmid = {37233606}, issn = {2305-6320}, abstract = {Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ[2] = 8.55, p = 0.033) and type of surgery (χ[2] = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.}, } @article {pmid37233002, year = {2023}, author = {Trivedi, J and Chourasia, A}, title = {Sodium Salt of Partially Carboxymethylated Sodium Alginate-g-Poly(acrylonitrile): I. Photo-Induced Synthesis, Characterization, and Alkaline Hydrolysis.}, journal = {Gels (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {37233002}, issn = {2310-2861}, support = {F-No.40-93/2011//University Grants Commission/ ; }, abstract = {An efficient redox initiating system, ceric ammonium nitrate/nitric acid, has been employed for the first time to carry out photo-induced graft copolymerization of acrylonitrile (AN) onto sodium salt of partially carboxymethylated sodium alginate, having an average degree of substitution value to be 1.10. The photo-grafting reaction conditions for maximum grafting have been systematically optimized by varying the reaction variables such as reaction time, temperature, the concentration of acrylonitrile monomer, ceric ammonium nitrate, and nitric acid, as well as the amount of the backbone. The optimum reaction conditions are obtained with a reaction time of 4 h, reaction temperature of 30 °C, acrylonitrile monomer concentration of 0.152 mol/L, initiator concentration of 5 × 10[-3] mol/L, nitric acid concentration of 0.20 mol/L, amount of backbone of 0.20 (dry basis) and the total volume of the reaction system of 150 mL. The highest percentage of grafting (%G) and grafting efficiency (%GE) achieved are 316.53% and 99.31%, respectively. The optimally prepared graft copolymer, sodium salt of partially carboxymethylated sodium alginate-g-polyacrylonitrile (%G = 316.53), has been hydrolyzed in an alkaline medium (0.7N NaOH, 90-95 °C for ~2.5 h) to obtain the superabsorbent hydrogel, H-Na-PCMSA-g-PAN. The chemical structure, thermal characteristics, and morphology of the products have also been studied.}, } @article {pmid37232999, year = {2023}, author = {Trivedi, J and Chourasia, A}, title = {Sodium Salt of Partially Carboxymethylated Sodium Alginate-Graft-Poly(Acrylonitrile): II Superabsorbency, Salt Sensitivity and Swelling Kinetics of Hydrogel, H-Na-PCMSA-g-PAN.}, journal = {Gels (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {37232999}, issn = {2310-2861}, support = {F.No. 40-93/2011//University Grants Commission/ ; }, abstract = {The water absorption measurements of a novel superabsorbent anionic hydrogel, H-Na-PCMSA-g-PAN, has been reported first time in water with a poor conductivity, 0.15 M saline (NaCl, CaCl2, and AlCl3) solutions, and simulated urine (SU) solutions at various times. The hydrogel has been prepared by the saponification of the graft copolymer, Na-PCMSA-g-PAN (%G = 316.53, %GE = 99.31). Results indicated that as compared to the swelling capacity values evaluated in water with a poor conductivity, the ability of the hydrogel to swell in various saline solutions with the same concentration is significantly reduced at all different durations. The swelling tends to be Na[+] > Ca[2+] > Al[3+] at the same saline concentration in the solution. Studies of the absorbency in various aqueous saline (NaCl) solutions also revealed that the swelling capacity decreased as the ionic strength of the swelling medium rose, which is consistent with the experimental results and Flory's equation. Furthermore, the experimental results strongly suggested that second-order kinetics governs the swelling process of the hydrogel in various swelling media. The swelling characteristics and equilibrium water contents for the hydrogel in various swelling media have also been researched. The hydrogel samples have been successfully characterized by FTIR to show the change in chemical environment to COO[-] and CONH2 groups after swelling in different swelling media. The samples have also been characterized by SEM technique.}, } @article {pmid37228888, year = {2023}, author = {Ayandipo, OO and Ogun, GO and Adepoju, OJ and Afuwape, OO and Fatunla, EO and Orunmuyi, AT}, title = {Immunohistochemical Profiling of HER-2/neu, Steroid Hormone Receptors and KI-67 Biomarkers in A Cohort of Nigerian Women with Breast Cancer.}, journal = {Journal of the West African College of Surgeons}, volume = {13}, number = {2}, pages = {7-15}, pmid = {37228888}, issn = {2276-6944}, abstract = {BACKGROUND: Progressive improvement in the accuracy of profiling of hormone receptors in breast cancer provides the basis for targeted endocrine therapy, a major pillar of multimodal breast cancer treatment. However, the disparity in findings from comparatively smaller sample-sized studies in West Africa has led to somewhat conflicting conclusions and recommendations.

OBJECTIVES: This study investigates the immunohistochemical (IHC) profile of breast cancer specimens for estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor-2 (HER2)/neu, and Ki-67 in a tertiary hospital in Ibadan, Nigeria over 12 years.

MATERIALS AND METHODS: We reviewed 998 IHC reports, documented clinicopathologic parameters, computed patterns of biomarkers, and stratified them based on the American Society of Clinical Oncology/College of American Pathologists recommendations. Descriptive analysis including frequency, mean, and median were generated from the data extracted.

RESULTS: Out of the 998 cases, 975 (97.7%) were females and 23 (2.3%) were males. The mean age was 48.84 ± 11.99 years. Open biopsies were the most common types of specimens (320, 41.6%): lumpectomy and incisional biopsy of ulcerated, fungating or unresectable tumours. In those cases, 246 (32.0%) were samples of breast-conserving or ablative surgical extirpation (mastectomy/wide local excision/quadrantectomy), and 203 (26.4%) were obtained by core needle biopsies. Invasive ductal carcinoma was the most common histopathological type (673, 94.5%). The majority of graded tumours were intermediate grade (444, 53.5%). Four hundred and sixty-nine (48.4%) were ER positive, 414 (42.8%) were PR positive, and 180 (19.4%) were HER2/neu positive. Three hundred and thirty-four (34.0%) were triple-negative. Eighty-nine cases had Ki-67 staining done, and of these 61 (68.5%) had positive nuclear staining.

CONCLUSION: Steroid hormone receptors and HER-2/neu proportions in our cohort are likely to be more representative than the widely varied figures hitherto reported in the sub-region. We advocate routine IHC analysis of breast cancer samples as a guide to personalized endocrine therapy.}, } @article {pmid37226494, year = {2023}, author = {Yoshida, H and Hiranuma, K and Nakahara, M and Kobayashi-Kato, M and Tanase, Y and Uno, M and Shiraishi, K and Ishikawa, M and Kato, T}, title = {Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969231177256}, doi = {10.1177/10668969231177256}, pmid = {37226494}, issn = {1940-2465}, abstract = {Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology.}, } @article {pmid37222952, year = {2023}, author = {Abdollahi, E and Mozdarani, H and Alizadeh, BZ}, title = {Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {5}, pages = {714-726}, pmid = {37222952}, issn = {1880-4233}, support = {Grant Number: IG-39711//Tarbiat Modares University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/radiotherapy ; Leukocytes, Mononuclear ; Apoptosis/genetics ; *Carcinoma ; *Drug-Related Side Effects and Adverse Reactions ; *MicroRNAs/genetics ; Cell Proliferation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Forkhead Box Protein O3/genetics ; }, abstract = {Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.}, } @article {pmid37217416, year = {2023}, author = {Rummel, KA and Gao, RW and Francis, LN and Petersen, IA and Mutter, RW and Corbin, KS}, title = {Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.}, journal = {Brachytherapy}, volume = {22}, number = {4}, pages = {487-490}, doi = {10.1016/j.brachy.2023.04.007}, pmid = {37217416}, issn = {1873-1449}, abstract = {PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.

METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.

RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.

CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.}, } @article {pmid37211759, year = {2023}, author = {Moradpour, M and Azizinik, F and Zeidabadi, H and Ghomi, Z and Shakki Katouli, F and Tavakol, E and Torabi Parizi, S}, title = {The imaging findings and diagnostic value of radiology modalities to assess breast malignancy among women aged younger than 30 years.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {64}, number = {8}, pages = {2363-2370}, doi = {10.1177/02841851231176271}, pmid = {37211759}, issn = {1600-0455}, mesh = {Female ; Humans ; Ultrasonography, Mammary/methods ; Sensitivity and Specificity ; *Breast Neoplasms/pathology ; Mammography/methods ; Magnetic Resonance Imaging/methods ; *Radiology ; }, abstract = {BACKGROUND: Breast cancer mainly affects women aged >50 years; however, younger women may also have advanced breast cancer, so early detection is important.

PURPOSE: To collect and review the imaging findings of women aged <30 years with breast cancer to find better diagnostic approaches for the early diagnosis of breast cancer in young women.

MATERIAL AND METHODS: In this study, 45 patients aged <30 years with a diagnosis of breast cancer were evaluated. Imaging assessments were performed based on ultrasound, mammography, and magnetic resonance imaging (MRI) findings. Finally, the findings were compared with the pathological results.

RESULTS: Predominant findings in ultrasound included irregular spiculated mass in 59.4%. In mammography, irregular high-density mass (46.5%) and suspicious micro calcification (42.8%) were the most common findings. In MRI, the predominant feature was a heterogeneous enhancing mass with an irregular shape and irregular margin (81%) with a 45% plateau and 36% washout kinetic pattern. In the pathology assessment, invasive ductal carcinoma was the most common finding (84.4%). All three modalities-MRI, ultrasonography, and mammography-are valuable, with sensitivities of 100%, 93.3%, and 90%, respectively.

CONCLUSION: Ultrasound, mammography, and MRI are highly sensitive and accurate tools for detecting breast cancer lesions in young women. Regular clinical breast examination with breast self-examination, and in suspected cases, ultrasound as the first imaging modality followed by mammography and/or MRI are the preferred diagnostic approach.}, } @article {pmid37210429, year = {2023}, author = {Joshi, U and Budhathoki, P and Gaire, S and Yadav, SK and Shah, A and Adhikari, A and Choong, G and Couzi, R and Giridhar, KV and Leon-Ferre, RA and Boughey, JC and Hieken, TJ and Mutter, R and Ruddy, KJ and Haddad, TC and Goetz, MP and Couch, FJ and Yadav, S}, title = {Clinical outcomes and prognostic factors in triple-negative invasive lobular carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {200}, number = {2}, pages = {217-224}, pmid = {37210429}, issn = {1573-7217}, support = {K12CA090628//Mayo Clinic/ ; P50CA116201//Mayo Clinic/ ; }, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; Prognosis ; *Carcinoma, Ductal, Breast/pathology ; Mastectomy ; }, abstract = {PURPOSE: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined.

METHODS: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy.

RESULTS: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001).

CONCLUSION: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.}, } @article {pmid37204630, year = {2023}, author = {Ito, Y and Fujii, K and Saito, M and Banno, H and Ido, M and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Invasive lobular carcinoma of the breast detected with real-time virtual sonography: a case report.}, journal = {Surgical case reports}, volume = {9}, number = {1}, pages = {85}, pmid = {37204630}, issn = {2198-7793}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) sometimes presents with unique clinical, pathologic, and radiographic features. In this case report, we describe a patient with ILC, whose initial presentation consisted with symptoms secondary to bone-marrow dissemination. In addition, the breast primary was revealed only by magnetic resonance imaging (MRI) followed by real-time virtual sonography (RVS).

CASE PRESENTATION: A 51-year-old woman presented to our outpatient clinic with dyspnea on exertion. She had severe anemia (hemoglobin, 5.3 g/dL) and thrombocytopenia (platelet count, 31 × 10[3]/mL). Bone-marrow biopsy was performed to evaluate hematopoietic function. The pathologic diagnosis was bone-marrow carcinomatosis due to metastatic breast cancer. Initial mammography followed by ultrasonography (US) failed to detect the primary tumor. On MRI, a non-mass-enhancement lesion was observed. While second-look US also did not detect the lesion, it was clearly visualized with RVS. We were finally able to biopsy the breast lesion. The pathologic diagnosis was ILC positive for both estrogen receptor and progesterone receptor, with 1 + immunohistochemical staining for human epidermal growth factor receptor 2. This case of ILC was characterized by bone-marrow metastasis. Due to decreased cell adhesion, the risk of bone-marrow metastasis is higher in ILC than in invasive ductal carcinoma, the most prevalent type of breast cancer. Biopsy of the primary lesion, which was initially only detected with MRI, was successfully performed with clear visualization during RVS, which is based on the fusion of MRI and US images.

CONCLUSION: In this case report and literature review, we describe the unique clinical characteristics of ILC and a strategy for identifying primary lesions that are initially only visualized with MRI.}, } @article {pmid37202608, year = {2023}, author = {Shawky, A and Sabit, H and Nazih, M and Baraka, K and El-Zawahry, M}, title = {CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {2}, pages = {374-383}, pmid = {37202608}, issn = {2210-6014}, mesh = {Humans ; *Cardiovascular Diseases ; Clopidogrel/adverse effects/metabolism/therapeutic use ; Cytochrome P-450 CYP2C19/genetics/metabolism ; Egypt/epidemiology ; *Myocardial Ischemia/genetics/therapy/chemically induced ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/adverse effects/metabolism/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.

METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded.

RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution.

CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.}, } @article {pmid37201361, year = {2023}, author = {Mekni, K and Mejri, O and Ayadi, A and ElFekif, C}, title = {Unexpected association between breast cancer and molar pregnancy in a 52-year-old woman: A case report.}, journal = {International journal of surgery case reports}, volume = {107}, number = {}, pages = {108253}, pmid = {37201361}, issn = {2210-2612}, abstract = {INTRODUCTION: There was no prior discussion about the association between breast cancer and molar pregnancy, particularly at an advanced age. Through our case and a systematic review, we will discuss the relevance of ovarian castration in hormone-receptor-positive breast cancer.

CASE PRESENTATION: We reported the case of a 52-year-old woman, not yet menopausal, who was diagnosed with a right breast tumor classified as BI-RADS category 4. The anatomopathological analysis of mammary biopsy revealed an invasive ductal carcinoma of no special type (grade 2). Hormone receptors were positive. It was a HER2-negative Breast cancer. It was then decided to treat the patient with radical surgery followed by chemotherapy, radiotherapy, and hormonotherapy. The patient had a "Patey operation". The postoperative course was without significant complications. No medical or surgical castration was indicated in the expectation that chemotherapy would cause ovarian failure. Unlikely, during chemotherapy course our patient developed a molar pregnancy.

CLINICAL DISCUSSION: Our case illustrates the possibility of pregnancy in non-menopausal women with estrogen-receptor-positive breast cancer. The combination of tamoxifen or aromatase inhibitors with ovarian suppression as standard adjuvant therapy may be recommended in such cases.

CONCLUSIONS: Ovarian function suppression in non-menopausal women with hormone receptor-positive breast cancer seems to be necessary. So that, we can avoid unexpected manifestations like molar pregnancy.}, } @article {pmid37201100, year = {2023}, author = {Koçberber, Z and Willemsen, N and Bartelt, A}, title = {The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1176733}, pmid = {37201100}, issn = {1664-2392}, mesh = {Animals ; Mice ; *Adipocytes, Brown/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Adipose Tissue, Brown/metabolism ; Adipogenesis/genetics ; Temperature ; Nuclear Proteins/metabolism ; }, abstract = {INTRODUCTION: Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.

METHODS: We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.

RESULTS: We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.

DISCUSSION: In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.}, } @article {pmid37200388, year = {2023}, author = {Amer, NN and Khairat, R and Hammad, AM and Kamel, MM}, title = {DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0284455}, pmid = {37200388}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Neoplasm Proteins/genetics ; RNA, Messenger/genetics ; Prognosis ; Disease Progression ; Biomarkers, Tumor/genetics/analysis ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes.

MATERIALS AND METHODS: A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data.

RESULTS: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades.

CONCLUSION: This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.}, } @article {pmid37198611, year = {2023}, author = {Abdulraheem, AM and Naji, D and Al Heyasat, AN and Alhasan, M and Almasri, NM and Odeh, R}, title = {Breast cancer with scalp metastases: a case report.}, journal = {Journal of medical case reports}, volume = {17}, number = {1}, pages = {203}, pmid = {37198611}, issn = {1752-1947}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/pathology ; Scalp/pathology ; Mastectomy ; *Skin Neoplasms/pathology ; *Carcinoma, Ductal, Breast/therapy ; }, abstract = {BACKGROUND: While breast cancer is the most common cancer in women, cutaneous metastases are rare in breast cancer. Additionally, scalp involvement in breast cancer metastasis is extremely rare. That being said, scalp lesions should always be thoroughly investigated to distinguish metastatic lesions from other neoplasms.

CASE PRESENTATION: A 47-year-old female Middle-Eastern patient presented with metastatic breast cancer in the lungs, bone, liver, and brain with no signs of multiple organ failure, in addition to cutaneous metastases, including the scalp. Between 2017 and 2022, she was managed through modified radical mastectomy, radiotherapy, and several lines of chemotherapy. She presented in September of 2022 with enlarging scalp nodules, which started developing 2 months prior to her presentation. Physical examination revealed firm, non-tender, and immobile skin lesions. Magnetic resonance imaging scan of the head showed soft tissue nodules in different sequences. A punch biopsy was taken from the largest scalp lesion and showed metastatic invasive ductal carcinoma. A panel of immunohistochemistry stains was applied, because a single specific marker for differentiating primary cutaneous adnexal tumors or other malignant neoplasms from breast cancer has not yet been identified. The panel showed positive estrogen receptor 95%, progesterone receptor 5%, negative human epidermal growth factor receptor 2, positive GATA binding protein 3, positive cytokeratin-7, negative P63, and negative KIT (CD117).

CONCLUSION: Breast cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. However, such lesions warrant a comprehensive radiologic and pathologic workup to rule out other possibilities of skin pathologies, such as sebaceous skin adenocarcinoma as it effects the management plan.}, } @article {pmid37195240, year = {2023}, author = {Murata, S and Yamashita, H and Kido, S and Harada, D and Ohtsuru, S and Sato, N}, title = {DYNAMIC METABOLIC CHANGES OBSERVED IN AN LPS-INDUCED SYSTEMIC INFLAMMATION RAT MODEL USING CONTINUOUS LONG-TERM INDIRECT CALORIMETRY EXPERIMENTS.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {1}, pages = {130-136}, pmid = {37195240}, issn = {1540-0514}, mesh = {Humans ; *Lipopolysaccharides/toxicity ; Calorimetry, Indirect/methods ; *Critical Illness ; Energy Metabolism/physiology ; Critical Care ; }, abstract = {Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.}, } @article {pmid37190710, year = {2023}, author = {Shahid, A and Mushtaq, S and Maqbool, H and Hassan, U and Hussain, M and Syed, M}, title = {Grading Intraductal Carcinoma of the Prostate; ISUP versus GUPS Recommendations.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {33}, number = {4}, pages = {396-399}, doi = {10.29271/jcpsp.2023.04.396}, pmid = {37190710}, issn = {1681-7168}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/pathology ; Biopsy ; Neoplasm Grading ; Prostatectomy ; }, abstract = {OBJECTIVE: To evaluate the frequency of intraductal component (IDC-P) in prostatic adenocarcinoma and its effect on the final grade using the ISUP and GUPS grading system.

STUDY DESIGN:  Descriptive study. Place and Duration of the Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, between June 2021 and June 2022.

METHODOLOGY: The study included 250 cases of prostatic adenocarcinoma. The presence of the intraductal carcinoma prostate (IDC-P) was confirmed by patchy or complete staining of the basal cell layer by p63 immunohistochemical stain. Cases with IDC-P were then graded using two different methods, first using the grading criteria based on the ISUP recommendations and then by the grading criteria based on the GUPS recommendations.

RESULTS: Two hundred and fifty cases showed invasive prostatic carcinoma ranging from Gleason grade group 2-5. IDC-P was identified in 5 of the 250 biopsies (2%). The final Gleason grade remained unchanged in these cases, when they were graded using the ISUP and GUPS recommendations.

CONCLUSION:  Although the present results are based on a relatively small sample size, IDC-P was not frequently present in biopsies of patients with adenocarcinoma in the studied population. Grading IDC-P in invasive prostate cancer led to only a minor change in grade group assignment of prostate cancer biopsies.

KEY WORDS:  Prostatic adenocarcinoma, Intraductal carcinoma, IDC-P, ISUP, GUPS, Gleason Grade group.}, } @article {pmid37190690, year = {2023}, author = {Zehra, T and Shams, M and Ahmad, Z and Chundriger, Q and Ahmed, A and Jaffar, N}, title = {Ki-67 Quantification in Breast Cancer by Digital Imaging AI Software and its Concordance with Manual Method.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {33}, number = {5}, pages = {544-547}, doi = {10.29271/jcpsp.2023.05.544}, pmid = {37190690}, issn = {1681-7168}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Ki-67 Antigen ; Retrospective Studies ; Artificial Intelligence ; Reproducibility of Results ; Software ; }, abstract = {OBJECTIVE: To validate the concordance of automated detection of Ki67 in digital images of breast cancer with the manual eyeball / hotspot method.

STUDY DESIGN: Descriptive study. Place and Duration of the Study: Jinnah Sindh Medical University, Karachi, from 1st January to 15th February 2022.

METHODOLOGY: Glass slides of cases diagnosed as invasive ductal carcinoma (IDC) were obtained from the Agha Khan Medical University Hospital, selected retrospectively and randomly from 60 patients. They were stained with the Ki67 antibody. An expert pathologist evaluated the Ki67 index in the hotspot fields using eyeball method. Digital images were taken from the hotspots using a camera attached to the microscope. The images were uploaded in the Mindpeak software to detect the exact percentage of Ki67-positive cells. The results obtained through automated detection were compared with the results reported by expert pathologists to see the differential outcome.

RESULTS: The manual and automated scoring methods showed strong positive concordance (p <0.001).

CONCLUSION: Automated scoring of Ki-67 staining has tremendous potential as the issues of lack of consistency, reproducibility, and accuracy can be eliminated. In the era of personalised medicine, pathologists can efficiently give a precise clinical diagnosis with the support of AI.

KEY WORDS: Artificial intelligence, Algorithms, Breast cancer, Deep learning, Image detection, Ki-67.}, } @article {pmid37190184, year = {2023}, author = {Bernhardt, SM and Mitchell, E and Stamnes, S and Hoffmann, RJ and Calhoun, A and Klug, A and Russell, TD and Pennock, ND and Walker, JM and Schedin, P}, title = {Isogenic Mammary Models of Intraductal Carcinoma Reveal Progression to Invasiveness in the Absence of a Non-Obligatory In Situ Stage.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190184}, issn = {2072-6694}, support = {R01CA169175/CA/NCI NIH HHS/United States ; PDF17480342/KOMEN/Susan G. Komen/United States ; }, abstract = {In breast cancer, progression to invasive ductal carcinoma (IDC) involves interactions between immune, myoepithelial, and tumor cells. Development of IDC can proceed through ductal carcinoma in situ (DCIS), a non-obligate, non-invasive stage, or IDC can develop without evidence of DCIS and these cases associate with poorer prognosis. Tractable, immune-competent mouse models are needed to help delineate distinct mechanisms of local tumor cell invasion and prognostic implications. To address these gaps, we delivered murine mammary carcinoma cell lines directly into the main mammary lactiferous duct of immune-competent mice. Using two strains of immune-competent mice (BALB/c, C57BL/6), one immune-compromised (severe combined immunodeficiency; SCID) C57BL/6 strain, and six different murine mammary cancer cell lines (D2.OR, D2A1, 4T1, EMT6, EO771, Py230), we found early loss of ductal myoepithelial cell differentiation markers p63, α-smooth muscle actin, and calponin, and rapid formation of IDC in the absence of DCIS. Rapid IDC formation also occurred in the absence of adaptive immunity. Combined, these studies demonstrate that loss of myoepithelial barrier function does not require an intact immune system, and suggest that these isogenic murine models may prove a useful tool to study IDC in the absence of a non-obligatory DCIS stage-an under-investigated subset of poor prognostic human breast cancer.}, } @article {pmid37190147, year = {2023}, author = {Diop, MK and Molina, OE and Birlea, M and LaRue, H and Hovington, H and Têtu, B and Lacombe, L and Bergeron, A and Fradet, Y and Trudel, D}, title = {Leukocytic Infiltration of Intraductal Carcinoma of the Prostate: An Exploratory Study.}, journal = {Cancers}, volume = {15}, number = {8}, pages = {}, pmid = {37190147}, issn = {2072-6694}, support = {CRP-154487/CAPMC/CIHR/Canada ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive histological subtype of prostate cancer (PCa) detected in approximately 20% of radical prostatectomy (RP) specimens. As IDC-P has been associated with PCa-related death and poor responses to standard treatment, the purpose of this study was to explore the immune infiltrate of IDC-P. Hematoxylin- and eosin-stained slides from 96 patients with locally advanced PCa who underwent RP were reviewed to identify IDC-P. Immunohistochemical staining of CD3, CD8, CD45RO, FoxP3, CD68, CD163, CD209 and CD83 was performed. For each slide, the number of positive cells per mm[2] in the benign tissues, tumor margins, cancer and IDC-P was calculated. Consequently, IDC-P was found in a total of 33 patients (34%). Overall, the immune infiltrate was similar in the IDC-P-positive and the IDC-P-negative patients. However, FoxP3[+] regulatory T cells (p < 0.001), CD68[+] and CD163[+] macrophages (p < 0.001 for both) and CD209[+] and CD83[+] dendritic cells (p = 0.002 and p = 0.013, respectively) were less abundant in the IDC-P tissues compared to the adjacent PCa. Moreover, the patients were classified as having immunologically "cold" or "hot" IDC-P, according to the immune-cell densities averaged in the total IDC-P or in the immune hotspots. The CD68/CD163/CD209-immune hotspots predicted metastatic dissemination (p = 0.014) and PCa-related death (p = 0.009) in a Kaplan-Meier survival analysis. Further studies on larger cohorts are necessary to evaluate the clinical utility of assessing the immune infiltrate of IDC-P with regards to patient prognosis and the use of immunotherapy for lethal PCa.}, } @article {pmid37189694, year = {2023}, author = {Minic, Z and Li, Y and Hüttmann, N and Uppal, GK and D'Mello, R and Berezovski, MV}, title = {Lysine Acetylome of Breast Cancer-Derived Small Extracellular Vesicles Reveals Specific Acetylation Patterns for Metabolic Enzymes.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189694}, issn = {2227-9059}, support = {RGPIN-2020-05775//Natural Sciences and Engineering Research Council/ ; }, abstract = {Cancer-derived small extracellular vesicles have been proposed as promising potential biomarkers for diagnosis and prognosis of breast cancer (BC). We performed a proteomic study of lysine acetylation of breast cancer-derived small extracellular vesicles (sEVs) to understand the potential role of the aberrant acetylated proteins in the biology of invasive ductal carcinoma and triple-negative BC. Three cell lines were used as models for this study: MCF10A (non-metastatic), MCF7 (estrogen and progesterone receptor-positive, metastatic) and MDA-MB-231 (triple-negative, highly metastatic). For a comprehensive protein acetylation analysis of the sEVs derived from each cell line, acetylated peptides were enriched using the anti-acetyl-lysine antibody, followed by LC-MS/MS analysis. In total, there were 118 lysine-acetylated peptides, of which 22, 58 and 82 have been identified in MCF10A, MCF7 and MDA-MB-231 cell lines, respectively. These acetylated peptides were mapped to 60 distinct proteins and mainly identified proteins involved in metabolic pathways. Among the acetylated proteins identified in cancer-derived sEVs from MCF7 and MDA-MB-231 cell lines are proteins associated with the glycolysis pathway, annexins and histones. Five acetylated enzymes from the glycolytic pathway, present only in cancer-derived sEVs, were validated. These include aldolase (ALDOA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK1), enolase (ENO) and pyruvate kinase M1/2 (PKM). For three of these enzymes (ALDOA, PGK1 and ENO) the specific enzymatic activity was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study reveals that sEVs contain acetylated glycolytic metabolic enzymes that could be interesting potential candidates for early BC diagnostics.}, } @article {pmid37186041, year = {2023}, author = {Wei, S and Bao, M and Zhu, Y and Zhang, W and Jiang, L}, title = {Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.}, journal = {Environmental toxicology}, volume = {38}, number = {8}, pages = {1951-1967}, doi = {10.1002/tox.23821}, pmid = {37186041}, issn = {1522-7278}, support = {82103309//Youth Found of National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism/pathology ; *Lung Neoplasms/pathology ; Lung/pathology ; Signal Transduction ; Glycerophospholipids/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.

METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.

RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.

CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.}, } @article {pmid37182091, year = {2023}, author = {Alvarez Moreno, JC and He, J}, title = {Invasive Breast Carcinoma With Sebaceous Morphologic Pattern Showing Lymph Node Macrometastasis: A Case Report.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37365}, pmid = {37182091}, issn = {2168-8184}, abstract = {Invasive ductal carcinoma of no special type can present with various patterns. It is not possible to diagnose them through imaging alone. Microscopic examination is necessary to accurately identify and characterize them. The sebaceous pattern was historically considered a distinct subtype of breast carcinoma. However, the number of cases is relatively small and the prognosis has not been fully established. In this paper, we present a case of invasive ductal carcinoma with focal sebaceous features, which had a macrometastasis to the axillary lymph nodes showing the sebaceous morphology.}, } @article {pmid37178723, year = {2023}, author = {Ogawa, M and Kan, H and Urano, M and Kawai, T and Nakajima, H and Murai, K and Miyaji, H and Toyama, T and Hiwatashi, A}, title = {Three-compartment spectral diffusion analysis for breast cancer magnetic resonance imaging.}, journal = {Magnetic resonance imaging}, volume = {103}, number = {}, pages = {179-184}, doi = {10.1016/j.mri.2023.04.006}, pmid = {37178723}, issn = {1873-5894}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Retrospective Studies ; Magnetic Resonance Imaging ; Diffusion Magnetic Resonance Imaging/methods ; Motion ; }, abstract = {RATIONALE AND OBJECTIVES: To examine the diagnostic performance of a three-compartment diffusion model with the fixed cut-off diffusion coefficient (D) using magnetic resonance spectral diffusion analysis for differentiating between invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) and compare the conventional apparent D (ADC), and mean kurtosis (MK), with the tissue D (DIVIM), perfusion D (D*IVIM), and perfusion fraction (fIVIM) calculated by conventional intravoxel incoherent motion.

PATIENTS AND METHODS: This retrospective study included women who underwent breast MRI with eight b-value diffusion-weighted imaging between February 2019 and March 2022. Spectral diffusion analysis was performed; very-slow, cellular, and perfusion compartments were defined using cut-off Ds of 0.1 × 10[-3] and 3.0 × 10[-3] mm[2]/s (static water D). The mean D (Ds, Dc, Dp, respectively) and fraction F (Fs, Fc, Fp, respectively) for each compartment were calculated. ADC and MK values were also calculated; receiver operating characteristic analyses were performed.

RESULTS: Histologically confirmed 132 ICD and 62 DCIS (age range 31-87 [53 ± 11] years) were evaluated. The areas under the curve (AUCs) for ADC, MK, DIVIM, D*IVIM, fIVIM, Ds, Dc, Dp, Fs, Fc, and Fp were 0.77, 0.72, 0.77, 0.51, 0.67, 0.54, 0.78, 0.51, 0.57, 0.54, and 0.57, respectively. The AUCs for the model combining very-slow and cellular compartments and the model combining the three compartments were 0.81 each, slightly and significantly higher than for ADC, DIVIM, and Dc (P = 0.09-0.14); and MK (P < 0.05), respectively.

CONCLUSION: Three-compartment model analysis using the diffusion spectrum accurately differentiated IDC from DCIS; however, it was not superior to ADC and DIVIM. The diagnostic performance of MK was lower than that of the three-compartment model.}, } @article {pmid37171457, year = {2023}, author = {Traberg, WC and Uribe, J and Druet, V and Hama, A and Moysidou, CM and Huerta, M and McCoy, R and Hayward, D and Savva, A and Genovese, AMR and Pavagada, S and Lu, Z and Koklu, A and Pappa, AM and Fitzgerald, R and Inal, S and Daniel, S and Owens, RM}, title = {Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.}, journal = {Advanced healthcare materials}, volume = {}, number = {}, pages = {e2301194}, doi = {10.1002/adhm.202301194}, pmid = {37171457}, issn = {2192-2659}, support = {2018-CRG7-3709//King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR)/ ; //Cambridge Commonwealth, European & International Trust/ ; //Churchill College Cambridge/ ; DGE-1650441//National Science Foundation Graduate Research Fellowship/ ; 70481//Sloan Foundation/ ; EP/S022953/1//EPSRC Cambridge NanoDTC/ ; //Trinity College Cambridge/ ; EP/L015889/1//EPSRC CDT in Sensor Technologies and Applications/ ; }, abstract = {Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.}, } @article {pmid37170638, year = {2023}, author = {Antón Rodriguez, Á and Odriozola Herrán, A and Echavarría Rodríguez, VJ and Alonso Fernández, S}, title = {Secondary sclerosing cholangitis induced by systemic chemotherapy.}, journal = {Revista espanola de enfermedades digestivas}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2023.9653/2023}, pmid = {37170638}, issn = {1130-0108}, abstract = {There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and, rarely, chemotherapy (1,2). We present the case of a 52-year-old woman with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 for painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Because of these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution, she was not candidate to liver transplantation on account of recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.}, } @article {pmid37163201, year = {2023}, author = {Kuroda, H and Yoshizako, T and Yamamoto, N and Kataoka, Y and Hyakudomi, M and Itakura, M and Kaji, Y}, title = {A case of breast cancer: Suppression of lactation-related FDG uptake 2 days after cabergoline administration.}, journal = {Acta radiologica open}, volume = {12}, number = {5}, pages = {20584601231174611}, pmid = {37163201}, issn = {2058-4601}, abstract = {We present a case of a 35-year-old woman with breast cancer in lactation 3 months after childbirth, in which a lactation inhibitor was useful for 18F-FDG PET/CT examination. Via ultrasonography and biopsy with histopathology, we diagnosed the lesion in the upper region of the left breast as invasive ductal carcinoma. She stopped breastfeeding and was administered cabergoline to suppress lactation. Two days after the administration, 18F-FDG PET/CT revealed segmental uptake (10 cm in diameter) and no lactation-related uptakes. Dynamic MRI also revealed a segmental enhancement of the same size as 18F-FDG PET/CT. The lactation inhibitor was useful to delineate the extent of the lesion during the 18F-FDG PET/CT examination.}, } @article {pmid37160814, year = {2023}, author = {Hu, J and Lang, R and Zhao, W and Jia, Y and Tong, Z and Shi, Y}, title = {The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer.}, journal = {Breast cancer research and treatment}, volume = {200}, number = {1}, pages = {23-36}, pmid = {37160814}, issn = {1573-7217}, support = {18ZXXYSY00070//Natural Science Foundation of Tianjin-Science and Technology Correspondent Project/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Prognosis ; *Carcinoma, Squamous Cell ; }, abstract = {OBJECTIVE: Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients.

METHODS: We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients.

RESULTS: A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms.

CONCLUSIONS: MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.}, } @article {pmid37159793, year = {2023}, author = {Jaramillo, C and Nazario-Toole, A and Xia, H and Adams, T and Josey, M}, title = {Luminal-Type Invasive Carcinoma in Association With Microglandular Adenosis/Atypical Microglandular Adenosis: A Case Report and Molecular Comparison.}, journal = {Cureus}, volume = {15}, number = {4}, pages = {e37198}, pmid = {37159793}, issn = {2168-8184}, abstract = {Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement membrane. The glands percolate haphazardly through the breast parenchyma rather than maintaining a lobular architecture, typical of other forms of adenosis.MGA is a benign lesion though atypical forms have been well described, often in close association with carcinoma. MGA, atypical MGA (AMGA), and the vast majority of MGA-associated carcinomas (MGACA) are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) by immunohistochemistry. In light of these findings and early molecular studies, MGA is hypothesized to represent a clonal process and nonobligate precursor of basal-type breast carcinomas. We present the case of a 58-year-old woman and the first published molecular comparison of a luminal-type invasive ductal carcinoma with its associated MGA/AMGA. Analysis of small nucleotide variants (SNVs) revealed that 63% of the SNVs identified in the MGA were present in the AMGA while only 10% of them were present in the MGACA, suggesting a direct relationship between MGA and AMGA but not MGA and MGACA.}, } @article {pmid37159559, year = {2023}, author = {Mnikhovich, MV and Romanov, AV and Nguyen, TM and Bezuglova, TV and Pastukhova, DA}, title = {Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review.}, journal = {Ultrastructural pathology}, volume = {47}, number = {4}, pages = {261-270}, doi = {10.1080/01913123.2023.2209162}, pmid = {37159559}, issn = {1521-0758}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/blood supply/metabolism/pathology ; Microcirculation ; Electrons ; *Breast Neoplasms/pathology ; Extracellular Matrix/metabolism ; Tumor Microenvironment ; }, abstract = {Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.}, } @article {pmid37156698, year = {2023}, author = {Khosravi, S and Khayyamfar, A and Karimi, J and Tutuni, M and Negahi, A and Akbari, ME and Nafissi, N}, title = {Machine Learning Approach for the Determination of the Best Cut-Off Points for Ki67 Proliferation Index in Adjuvant and Neo-Adjuvant Therapy Breast Cancer Patients.}, journal = {Clinical breast cancer}, volume = {23}, number = {5}, pages = {519-526}, doi = {10.1016/j.clbc.2023.03.015}, pmid = {37156698}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Ki-67 Antigen ; Neoadjuvant Therapy ; Receptors, Progesterone ; Cell Proliferation ; Prognosis ; Receptor, ErbB-2 ; }, abstract = {BACKGROUND: This study aims to evaluate Ki67 cut-off points for differentiating low and high-risk patients based on survival and recurrence and find the best Ki67 cut-off points in breast cancer patients undergoing adjuvant and neoadjuvant therapy using machine learning methods.

PATIENTS AND METHODS: Patients with breast cancer treated at 2 referral hospitals between December 2000 and March 2021 who had invasive breast cancer entered this study. There were 257 patients in the neoadjuvant group and 2139 in the adjuvant group. A decision tree method was used to predict the likelihood of survival and recurrence. The 2-ensemble technique of RUSboost and bagged tree were imposed on the decision tree method to increase the accuracy of the determination. 80 percent of the data was used to train and validate the model, and 20% was used as a test.

RESULTS: In adjuvant therapy breast cancer patients with Invasive ductal carcinoma (IDC) and Invasive lobular carcinoma (ILC) the cutoff points for survival were 20 and 10, respectively. For luminal A, luminal B, Her2 neu, and triple-negative adjuvant therapy patients' the cutoff points for survival were 25, 15, 20, and 20, respectively. For neoadjuvant therapy luminal A and luminal B group, survival cutoff points were 25 and 20, respectively.

CONCLUSION: Despite variability in measurement and cut-off points, the Ki-67 proliferation index is still helpful in the clinic. Further investigation is needed to determine the best cut-off points for different patients. The sensitivity and specificity of Ki-67 cutoff point prediction models in this study could further prove its significance as a prognostic factor.}, } @article {pmid37146126, year = {2023}, author = {Ma, Q and Zhang, J and Qi, W and Li, Z and Jiang, Y and Zhang, M and He, H and Su, K and Shi, H}, title = {Store-Operated Ca[2+] Channels Contribute to the Generation of Ca[2+] Waves in Interdental Cells in the Cochleae.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {10}, pages = {1896-1904}, doi = {10.1021/acschemneuro.3c00161}, pmid = {37146126}, issn = {1948-7193}, mesh = {*Cochlea ; *Spiral Ganglion/physiology ; Neurons ; }, abstract = {Cochlear calcium (Ca[2+]) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca[2+] waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca[2+] waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca[2+] wave formation and propagation by developing a single-cell Ca[2+] excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca[2+] excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca[2+] channels in IDCs are responsible for Ca[2+] wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca[2+] waves. Our results provide the mechanism of Ca[2+] formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca[2+] waves in the cochlea, with good potential for research on cochlear Ca[2+] and hearing functions.}, } @article {pmid37143728, year = {2023}, author = {Cipolletti, M and Leone, S and Bartoloni, S and Acconcia, F}, title = {A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1129162}, pmid = {37143728}, issn = {1664-2392}, mesh = {Female ; Humans ; Estrogen Receptor alpha/genetics/metabolism ; Biosynthetic Pathways ; Neoplasm Recurrence, Local ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast ; Purines ; *Carbon-Nitrogen Ligases/metabolism ; Phosphoribosylglycinamide Formyltransferase/metabolism ; }, abstract = {Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.}, } @article {pmid37140551, year = {2023}, author = {van der Slot, MA and Remmers, S and Kweldam, CF and den Bakker, MA and Nieboer, D and Busstra, MB and Gan, M and Klaver, S and Rietbergen, JBW and van Leenders, GJLH and , }, title = {Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.}, journal = {Histopathology}, volume = {83}, number = {3}, pages = {348-356}, doi = {10.1111/his.14934}, pmid = {37140551}, issn = {1365-2559}, support = {//BeterKeten Foundation/ ; }, mesh = {Male ; Humans ; *Prostate/surgery/pathology ; Margins of Excision ; Tumor Burden ; Neoplasm Invasiveness/pathology ; *Prostatic Neoplasms/surgery/pathology ; Biopsy ; Prostatectomy/adverse effects/methods ; }, abstract = {AIMS: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP.

METHODS AND RESULTS: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not.

CONCLUSIONS: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.}, } @article {pmid37140069, year = {2023}, author = {Nonnemacher, CJ and Dale, P and Scott, A and Bonner, M}, title = {Pathologic Tumor Size versus Mammography, Sonography, and MRI in Breast Cancer Based on Pathologic Subtypes.}, journal = {The American surgeon}, volume = {89}, number = {8}, pages = {3652-3654}, doi = {10.1177/00031348231174019}, pmid = {37140069}, issn = {1555-9823}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Mammography ; Magnetic Resonance Imaging/methods ; }, abstract = {INTRODUCTION: The standard of care for imaging of breast pathology has historically been mammography and sonography. MRI is a modern adjunct in the surgeon's toolkit. We looked to examine the differences in imaging modalities and their ability to predict the size in relation to the pathologic size after excision with focus on pathologic subtypes.

METHODS: We analyzed patient records across a 4-year period from 2017 to 2021 who were treated surgically for breast cancer at our facility. We used a retrospective chart review to collect measurements that were recorded of the tumors by the radiologist for available mammography, ultrasound, and MRI which were compared to pathology report measurements of the final specimens. We subdivided the results by pathologic subtypes including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS).

RESULTS: 658 total patients met criteria for analysis. Mammography overestimated specimens with DCIS by 1.93 mm (P = .15), US underestimated by .56 (.55), and MRI overestimated by 5.77 mm (P < .01). There was no statistically significant difference in any modalities with IDC. With specimens of ILC, all 3 imaging modalities underestimated tumor size, with only US being significant.

DISCUSSION: Mammography and MRI consistently overestimated tumor size with the exception of ILC while US underestimated tumor size on all pathologic subtypes. MRI significantly overestimated tumor size in DCIS by 5.77 mm. Mammography was the most accurate imaging modality for all pathologic subtypes and never had a statistically significant difference from actual tumor size.}, } @article {pmid37139855, year = {2023}, author = {Tsilingiris, D and Schimpfle, L and von Rauchhaupt, E and Sulaj, A and Seebauer, L and Bartl, H and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z}, title = {Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {108}, number = {10}, pages = {e979-e988}, pmid = {37139855}, issn = {1945-7197}, mesh = {Humans ; Male ; *Diabetes Mellitus, Type 2/complications ; *Metabolic Syndrome/complications/epidemiology ; *Peripheral Nervous System Diseases/epidemiology/etiology ; *Insulin Resistance ; Glycation End Products, Advanced ; }, abstract = {AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.

METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.

RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).

CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.}, } @article {pmid37129492, year = {2023}, author = {Berg, WA and López Aldrete, AL and Jairaj, A and Ledesma Parea, JC and García, CY and McClennan, RC and Cen, SY and Larsen, LH and de Lara, MTS and Love, S}, title = {Toward AI-supported US Triage of Women with Palpable Breast Lumps in a Low-Resource Setting.}, journal = {Radiology}, volume = {307}, number = {4}, pages = {e223351}, pmid = {37129492}, issn = {1527-1315}, support = {UH3 CA189966/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Artificial Intelligence ; Triage ; Prospective Studies ; Ultrasonography, Mammary/methods ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal ; }, abstract = {Background Most low- and middle-income countries lack access to organized breast cancer screening, and women with lumps may wait months for diagnostic assessment. Purpose To demonstrate that artificial intelligence (AI) software applied to breast US images obtained with low-cost portable equipment and by minimally trained observers could accurately classify palpable breast masses for triage in a low-resource setting. Materials and Methods This prospective multicenter study evaluated participants with at least one palpable mass who were enrolled in a hospital in Jalisco, Mexico, from December 2017 through May 2021. Orthogonal US images were obtained first with portable US with and without calipers of any findings at the site of lump and adjacent tissue. Then women were imaged with standard-of-care (SOC) US with Breast Imaging Reporting and Data System assessments by a radiologist. After exclusions, 758 masses in 300 women were analyzable by AI, with outputs of benign, probably benign, suspicious, and malignant. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. Results The mean patient age ± SD was 50.0 years ± 12.5 (range, 18-92 years) and mean largest lesion diameter was 13 mm ± 8 (range, 2-54 mm). Of 758 masses, 360 (47.5%) were palpable and 56 (7.4%) malignant, including six ductal carcinoma in situ. AI correctly identified 47 or 48 of 49 women (96%-98%) with cancer with either portable US or SOC US images, with AUCs of 0.91 and 0.95, respectively. One circumscribed invasive ductal carcinoma was classified as probably benign with SOC US, ipsilateral to a spiculated invasive ductal carcinoma. Of 251 women with benign masses, 168 (67%) imaged with SOC US were classified as benign or probably benign by AI, as were 96 of 251 masses (38%, P < .001) with portable US. AI performance with images obtained by a radiologist was significantly better than with images obtained by a minimally trained observer. Conclusion AI applied to portable US images of breast masses can accurately identify malignancies. Moderate specificity, which could triage 38%-67% of women with benign masses without tertiary referral, should further improve with AI and observer training with portable US. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Slanetz in this issue.}, } @article {pmid37124528, year = {2023}, author = {Zhang, N and Xiang, Y and Shao, Q and Wu, J and Liu, Y and Long, H and Tao, D and Zeng, X}, title = {Different risk and prognostic factors for liver metastasis of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1102853}, pmid = {37124528}, issn = {2234-943X}, abstract = {PURPOSE: The present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.

MATERIALS AND METHODS: Patients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan-Meier method.

RESULTS: In total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively.

CONCLUSIONS: De novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.}, } @article {pmid37121885, year = {2023}, author = {Ikegami, M}, title = {Prognostic benefit of comprehensive genomic profiling in clinical practice remains uncertain.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {3053-3055}, pmid = {37121885}, issn = {1349-7006}, support = {#22K15571//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/pathology ; Prognosis ; *Adenocarcinoma/genetics ; Retrospective Studies ; Genomics ; *Carcinoma, Pancreatic Ductal/genetics/therapy ; }, abstract = {The overall survival of patients who received genomically matched therapy was not significantly longer than that of patients receiving treatment only other than genomically matched therapy in the breast invasive ductal carcinoma (A), colorectal adenocarcinoma (B), and pancreatic adenocarcinoma (C) cohorts.}, } @article {pmid37113357, year = {2023}, author = {Takayasu, H and Kata, Y and Otsu, Y and Inoue, S and Kaneko, T}, title = {ALK-Rearranged NSCLC With Concomitant HER2-Mutant Breast Cancer Patient Treated With Alectinib, Trastuzumab, and Pertuzumab: A Case Report.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36711}, pmid = {37113357}, issn = {2168-8184}, abstract = {Multiple cancers are a common occurrence, and the choice of treatment can be a challenging decision. The current case report describes a 71-year-old woman with overlapping anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma and HER2-mutant breast cancer, who achieved improvement with concurrent use of the molecularly targeted agents Alectinib, Trastuzumab, and Pertuzumab. A 71-year-old woman was diagnosed with lung adenocarcinoma and brain metastases, and invasive ductal carcinoma of the right breast, HER2-mutant type. In March 2021, a biopsy confirmed the presence of the ALK fusion gene in lung cancer. In April 2021, he started Alectinib and showed shrinkage of lung cancer; in December 2021, a metastatic liver tumor was found, and a liver biopsy diagnosed liver metastasis of breast cancer. Therefore, Alectinib was discontinued in February 2022, and Trastuzumab, Pertuzumab, and Docetaxel were started as chemotherapy for breast cancer. She continued treatment with Trastuzumab and Pertuzumab, but in July 2022, she developed an increase in lung cancer. Her metastatic liver tumor continued shrinking, and she was started on Trastuzumab, Pertuzumab, and Alectinib. After six months of treatment, the patient showed a sustained reduction in both lung cancer, breast cancer, and brain metastases with no adverse events. ALK rearrangement lung cancer often develops in young women, and similarly, breast cancer often develops in women. Therefore, those cancers may occur simultaneously. In such cases, the choice of treatment can be difficult, as both cancers require different approaches. Alectinib has been shown to have a high response rate and prolonged progression-free survival in ALK-rearranged non-small cell lung cancer (NSCLC). Trastuzumab and Pertuzumab are commonly used for the treatment of HER2-mutant breast cancer and have been shown to significantly improve progression-free survival and overall survival. This case report provides evidence that the concurrent use of Alectinib, Trastuzumab, and Pertuzumab can be an effective treatment for patients with overlapping ALK-rearranged NSCLC and HER2-mutant breast cancer. It is important to consider concurrent treatment in patients with multiple cancers to optimize treatment outcomes and improve quality of life. However, further studies are needed to establish the safety and efficacy of this combination of drugs for the treatment of overlapping cancers.}, } @article {pmid37111277, year = {2023}, author = {Ballal, S and Yadav, MP and Roesch, F and Wakade, N and Raju, S and Sheokand, P and Mishra, P and Moon, ES and Tripathi, M and Martin, M and Bal, C}, title = {Head-to-Head Comparison between [[68]Ga]Ga-DOTA.SA.FAPi and [[18]F]F-FDG PET/CT Imaging in Patients with Breast Cancer.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {4}, pages = {}, pmid = {37111277}, issn = {1424-8247}, abstract = {This study aimed to compare the diagnostic performance of [[68]Ga]Ga-DOTA.SA.FAPi with that of [[18]F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer. [[18]F]F-FDG and [[68]Ga]Ga-DOTA.SA.FAPi PET/CT scans of histologically proven breast cancer patients were compared according to patient-based and lesion-based analysis. Forty-seven patients with a mean age of 44.8 ± 9.9 years (range: 31-66 years) were evaluated. A total of 85% of patients had invasive ductal carcinoma, and 15% had invasive lobular carcinoma. The tracer uptake [SULpeak, SULavg, and the median tumor-to-background ratio (TBR)] was significantly higher in [[68]Ga]Ga-DOTA.SA.FAPi than with [[18]F]F-FDG PET/CT for lymph nodes, pleural metastases, and liver lesions (p < 0.05). However, for brain metastasis, only the median TBR was significantly higher (p < 0.05) compared to [[18]F]F-FDG. In patient-based analysis the sensitivity of [[68]Ga]Ga-DOTA.SA.FAPi PET/CT was higher, but not significant than that of [[18]F]F-FDG PET/CT in the detection of both primary tumors and metastatic lesions. According to lesion-based analysis, on diagnostic CT, 47 patients had 44 primary tumors, 248 lymph nodes, 15 pleural, 88 liver, and 42 brain metastases. [[68]Ga]Ga-DOTA.SA.FAPi scan identified more abnormal lesions than [[18]F]F-FDG in all the primary and metastatic sites with a maximum marked difference in the primary site [88.6% vs. 81.8%; p-0.001], lymph nodes [89.1% vs. 83.8%; p-0.0001], pleural metastases [93.3% vs. 73%; p-0.096] and brain metastasis [100% vs. 59.5%; p-0.0001]. [[68]Ga]Ga-DOTA.SA.FAPi PET/CT was superior to [[18]F]F-FDG PET/CT in the imaging of breast cancers.}, } @article {pmid37104801, year = {2023}, author = {Bar-Kalifa, E and Goren, O and Gilboa-Schechtman, E and Wolff, M and Rafael, D and Heimann, S and Yehezkel, I and Scheniuk, A and Ruth, F and Atzil-Slonim, D}, title = {Clients' emotional experience as a dynamic context for client-therapist physiological synchrony.}, journal = {Journal of consulting and clinical psychology}, volume = {91}, number = {6}, pages = {367-380}, doi = {10.1037/ccp0000811}, pmid = {37104801}, issn = {1939-2117}, support = {//Israel Science Foundation/ ; }, mesh = {Humans ; *Psychotherapy ; Professional-Patient Relations ; Emotions/physiology ; *Emotional Regulation ; Databases, Factual ; }, abstract = {OBJECTIVE: Client-therapist physiological synchrony has recently attracted significant empirical attention. Recent theoretical accounts propose that physiological linkages should not be considered a stable dyadic virtue but rather a dynamic process that depends on the situational context in which they transpire. The present study adopted a "momentary" (vs. "global") approach that focuses on therapist-client physiological synchrony over relatively short periods of time. These temporal data served to examine the interplay between patterns of synchrony (in-phase vs. antiphase) and clients' momentary emotional experiences (inhibited/unproductive, productive, and positive). Synchrony was assessed by measuring respiratory sinus arrhythmia (RSA), an autonomic index that is known to be associated with interpersonal emotion regulation.

METHOD: Data were drawn from 28 clients undergoing a 16-session supportive-expressive dynamic therapy for depression. Clients' and therapists' electrocardiography were recorded in five sessions; clients' emotional experiences were coded at the speech-turn level. After each session, the clients also completed the session evaluation scale.

RESULTS: Client-therapist dyads had greater momentary RSA synchrony than would be predicted by chance. Compared to moments of unproductive emotional experience, greater antiphase synchrony was observed during moments of productive emotional experiences. In addition, compared to moments of unproductive emotional experience, greater in-phase and antiphase synchrony were observed during moments of positive emotional experiences. These patterns of synchrony were associated with clients' favorable evaluations of the session.

CONCLUSION: By considering the dynamic nature of synchrony, these findings provide a fine-grained picture of physiological synchrony and its potential effects on therapy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37103742, year = {2023}, author = {Jiao, Y and Guo, X and Lv, Q}, title = {Options of locoregional therapy for primary foci of breast cancer influence the rate of nonregional lymph node metastasis in N2-N3 status patients: a SEER database analysis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {647-656}, pmid = {37103742}, issn = {1880-4233}, support = {ZYJC18018//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; }, mesh = {Humans ; Aged, 80 and over ; Female ; *Breast Neoplasms/surgery/pathology ; Lymphatic Metastasis/pathology ; Prognosis ; Mastectomy ; Lymph Nodes/surgery/pathology ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {OBJECTIVE: We aim to use the SEER database to discuss the effect of various surgical methods of primary foci and other influencing factors on the nonregional lymph node (NRLN) metastasis in invasive ductal carcinoma (IDC) patients.

METHODS: Clinical information of IDC patients used in this study was obtained from the SEER database. The statistical analyses used included a multivariate logistic regression model, the chi-squared test, log-rank test and propensity score matching (PSM).

RESULTS: 243,533 patients were included in the analysis. 94.3% of NRLN patients had a high N positivity (N3) but an equal distribution in T status. The proportion of operation type, especially BCM and MRM, differed significantly between the N0-N1 and N2-N3 groups in the NRLN metastasis group and nonmetastasis group. Age > 80 years, positive PR, modified radical mastectomy (MRM)/radical mastectomy (RM) and radiotherapy for primary tumor were shown to be protective factors for NRLN metastasis, and higher N positivity was the most significant risk factors. N2-N3 patients receiving MRM had a lower metastasis to NRLN than those receiving BCM (1.4% vs 3.7%, P < 0.001), while this relevance was not discovered in N0-N1 patients. In N2-N3 patients, a better OS was observed in MRM group than BCM group (P < 0.001).

CONCLUSION: MRM exerted a protective effect on NRLN metastasis compared to BCM in N2-N3 patients but not N0-N1 patients. This implies the need for more consideration when choosing the operation methods of primary foci in patients with high N positivity.}, } @article {pmid37101747, year = {2023}, author = {Xiang, S and Wei, M and Zhao, L and Lin, A and Xiong, Z}, title = {Integrated Analyses of the Expression and Prognostic Value of EPHB6 in Cervical Cancer and Its Correlation with Immune Infiltrates.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {2258906}, pmid = {37101747}, issn = {1687-8450}, abstract = {Among women, cervical cancer (CC) ranks as the third most frequent form of carcinoma and the fourth greatest cancer-related cause of deaths. There is increasing evidence that points to the dysregulation of EPH receptor B6 (EPHB6) in various cancers. On the other hand, neither the expression nor the function of EPHB6 in CC has been researched. In the first part of this investigation, we analyzed the data from the TCGA and discovered that the level of EPHB6 was much lower in CC tissues than in normal cervical tissues. ROC assays revealed that high EPHB6 expression had an AUC value of 0.835 for CC. The survival study revealed that both the overall and disease-specific survivals in this condition were considerably lower among patients who had a low EPHB6 level compared to those who had a high EPHB6 level. It is important to note that the multivariate COX regression analysis indicated that the expression of EPHB6 was an independent predictive factor. In addition to this, the C-indexes and calibration plots of a nomogram derived from multivariate assays revealed an accurate prediction performance among patients with CC. Immune infiltration analysis indicated that the expression of EPHB6 was positively associated with the levels of Tcm, TReg, B cells, T cells, iDC, T helper cells, cytotoxic cells, and DC, while negatively associated with NK CD56bright cells and neutrophils. In summary, the downregulation of EPHB6 was strongly linked to a more aggressive clinical development of CC, suggesting its potential utility as a diagnostic and therapeutic target in CC.}, } @article {pmid37095978, year = {2023}, author = {Norooznezhad, AH and Yarani, R and Payandeh, M and Hoseinkhani, Z and Mahmoudi, H and Kiani, S and Mansouri, K}, title = {Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.}, journal = {Heliyon}, volume = {9}, number = {4}, pages = {e15165}, pmid = {37095978}, issn = {2405-8440}, abstract = {INTRODUCTION: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs).

CASE PRESENTATION: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp.

CONCLUSION: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.}, } @article {pmid37095044, year = {2023}, author = {Nelson, TJ and Kumar, A and Nalawade, V and Nonato, T and Shabaik, A and Roma, A and Rose, BS and McKay, RR}, title = {Associations Between Intraductal Prostate Cancer and Metastases Following Radical Prostatectomy in Men With Prostate Cancer in the Veterans Affairs Database.}, journal = {Clinical genitourinary cancer}, volume = {21}, number = {4}, pages = {452-458}, doi = {10.1016/j.clgc.2023.03.010}, pmid = {37095044}, issn = {1938-0682}, abstract = {PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases.

METHODS: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA >0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models.

RESULTS: Of 13,913 patients meeting inclusion criteria, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS ≥8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively.

CONCLUSIONS: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity.}, } @article {pmid37094629, year = {2023}, author = {Chovsepian, A and Prokopchuk, O and Petrova, G and Gjini, T and Kuzi, H and Heisz, S and Janssen, KP and Martignoni, ME and Friess, H and Hauner, H and Rohm, M}, title = {Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.}, journal = {Molecular metabolism}, volume = {73}, number = {}, pages = {101729}, pmid = {37094629}, issn = {2212-8778}, mesh = {Humans ; Cachexia/metabolism ; Retrospective Studies ; C-Reactive Protein ; *Diabetes Mellitus, Type 2/complications ; *Pancreatic Neoplasms/complications/metabolism ; Body Weight ; Obesity/complications ; Biomarkers ; *Colorectal Neoplasms/complications ; }, abstract = {OBJECTIVES: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.

METHODS: We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI ≥30 kg/m[2] was considered obese).

RESULTS: The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p ≤ 0.05), higher weight loss (8.9% vs. 6.0%, p ≤ 0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square = 4.96, p ≤ 0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919 μg/mL vs. 0.551 μg/mL, p ≤ 0.01) and interleukin 6 (5.98 pg/mL vs. 3.75 pg/mL, p ≤ 0.05) as well as lower serum albumin levels (3.98 g/dL vs. 4.18 g/dL, p ≤ 0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p ≤ 0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p ≤ 0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300 μg/mL vs. 0.571 μg/mL, p ≤ 0.0001; hemoglobin: 11.24 g/dL vs. 12.52 g/dL, p ≤ 0.05).

CONCLUSIONS: We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.}, } @article {pmid37092454, year = {2023}, author = {Neagu, AN and Whitham, D and Seymour, L and Haaker, N and Pelkey, I and Darie, CC}, title = {Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype.}, journal = {Proteomes}, volume = {11}, number = {2}, pages = {}, pmid = {37092454}, issn = {2227-7382}, abstract = {Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70-80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of the progression from intraductal pre-invasive malignant lesions of the breast, which characterize a ductal carcinoma in situ (DCIS), to IDC, are still poorly identified, validated, and clinically applied. In the era of "6P" medicine, it remains a great challenge to determine which patients should be over-treated versus which need to be actively monitored without aggressive treatment. The major difficulties for designating DCIS to IDC progression may be solved by understanding the integrated genomic, transcriptomic, and proteomic bases of invasion. In this review, we showed that multiple proteomics-based techniques, such as LC-MS/MS, MALDI-ToF MS, SELDI-ToF-MS, MALDI-ToF/ToF MS, MALDI-MSI or MasSpec Pen, applied to in-tissue, off-tissue, BC cell lines and liquid biopsies, improve the diagnosis of IDC, as well as its prognosis and treatment monitoring. Classic proteomics strategies that allow the identification of dysregulated protein expressions, biological processes, and interrelated pathway analyses based on aberrant protein-protein interaction (PPI) networks have been improved to perform non-invasive/minimally invasive biomarker detection of early-stage IDC. Thus, in modern surgical oncology, highly sensitive, rapid, and accurate MS-based detection has been coupled with "proteome point sampling" methods that allow for proteomic profiling by in vivo "proteome point characterization", or by minimal tissue removal, for ex vivo accurate differentiation and delimitation of IDC. For the detection of low-molecular-weight proteins and protein fragments in bodily fluids, LC-MS/MS and MALDI-MS techniques may be coupled to enrich and capture methods which allow for the identification of early-stage IDC protein biomarkers that were previously invisible for MS-based techniques. Moreover, the detection and characterization of protein isoforms, including posttranslational modifications of proteins (PTMs), is also essential to emphasize specific molecular mechanisms, and to assure the early-stage detection of IDC of the breast.}, } @article {pmid37092099, year = {2022}, author = {Al Nemer, A}, title = {Breast biomarkers profile of invasive lobular carcinoma in a cohort of arab women shows no significant differences from carcinoma of no special type.}, journal = {African health sciences}, volume = {22}, number = {4}, pages = {10-15}, pmid = {37092099}, issn = {1729-0503}, mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Lobular/epidemiology/diagnosis/pathology ; *Carcinoma, Ductal, Breast ; Ki-67 Antigen ; Retrospective Studies ; Arabs ; Receptors, Progesterone ; Receptors, Estrogen/metabolism ; *Breast Neoplasms/pathology ; Prognosis ; }, abstract = {OBJECTIVES: Invasive lobular carcinoma (ILC) of the breast is known for its common presentation at an older age, and the frequent expression of favourable profile of estrogen and progesterone receptors (ER & PR) positivity, and human epidermal growth factor receptor 2 (HER2) negativity combined with low proliferation rate as measured by Ki67. This study aimed to test these clinicopathological features of ILC in an Arabic cohort.

METHODS: All breast biopsies diagnosed as IDC or ILC were retrospectively reviewed over 2 years period (2017-2018) in an academic centre. Variables were compared using Fisher's exact test for statistical significance.

RESULTS: A total of 134 cases were recruited, 12.7% were ILC. The median age was 52 years for both types. Clustering of ILC cases was noticed in luminal A subtype (47.1%), but there was no statistically significant difference in subtyping between the 2 histologic groups. Ki67 was significantly lower in ILC than IDC category.

CONCLUSIONS: Our study showed that ILC in our cohort lacks the advantage of older age and the common high expression of ER positivity in comparison to IDC. There is, however, significant difference of the value of Ki67 proliferation marker. The prognosis of lobular morphology is questionable in our cohort.}, } @article {pmid37091166, year = {2023}, author = {Fang, WB and Medrano, M and Cote, P and Portsche, M and Rao, V and Hong, Y and Behbod, F and Knapp, JR and Bloomer, C and Noel-Macdonnell, J and Cheng, N}, title = {Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1130911}, pmid = {37091166}, issn = {2234-943X}, support = {R01 CA172764/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND/INTRODUCTION: As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.

GOALS: We sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression.

METHODS: Fibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells.

RESULTS: Through transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment.

CONCLUSION: DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.}, } @article {pmid37090301, year = {2023}, author = {Fakhry, J and Hanna, M}, title = {Low Radiologic Sensitivity in Detecting Radiation-Associated Breast Angiosarcoma (RAS).}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36508}, pmid = {37090301}, issn = {2168-8184}, abstract = {Due to its rarity, literature pertaining to radiation-associated breast angiosarcoma (RAS) remains sparse, with most studies focusing on retrospective review. Of more significant concern is the ambiguity of screening recommendations and modalities used to detect RAS, with current guidelines focusing on yearly mammographic imaging for women who underwent lumpectomy with radiation. Unfortunately, routine post-cancer screening has demonstrated low sensitivity in detecting RAS, often mistaking it for benign changes in roughly half of cases. We present an 83-year-old woman initially diagnosed with stage 1 invasive ductal carcinoma of the left breast who underwent a lumpectomy followed by radiation with 6040 cGy. Five years after her initial diagnosis, the patient noticed a suspicious lesion which then led her to undergo multiple modalities of imaging that described benign features. After continued concern, a biopsy was taken that demonstrated RAS of the left breast within the irradiated site. The patient underwent further radiation and declined surgical intervention. Routine screening with mammography and ultrasonography following breast radiation treatment are not sensitive modalities in detecting RAS. High-risk patient groups treated with greater than 0.5 Gy of radiation with concerning physical features 2-10 years after treatment should undergo MRI with biopsy at the initial concern to rule out angiosarcoma. Benign findings on imaging with patients in these groups should also consider biopsy.}, } @article {pmid37085500, year = {2023}, author = {Zhou, D and Li, M and Yasin, MH and Lu, Q and Fu, J and Jiang, K and Hong, R and Wang, S and Xu, F}, title = {The prognostic value and immune microenvironment association of AR in HER2+ nonmetastatic breast cancer.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {30}, pmid = {37085500}, issn = {2374-4677}, support = {320.6750.2021-10-97//Ministry of Health of China | Wu Jieping Medical Foundation/ ; 2019A1515011945//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, abstract = {This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.}, } @article {pmid37085014, year = {2023}, author = {van Balkom, IDC and Burdeus-Olavarrieta, M and Cooke, J and de Cuba, AG and Turner, A and , and Vogels, A and Maruani, A}, title = {Consensus recommendations on mental health issues in Phelan-McDermid syndrome.}, journal = {European journal of medical genetics}, volume = {66}, number = {6}, pages = {104770}, doi = {10.1016/j.ejmg.2023.104770}, pmid = {37085014}, issn = {1878-0849}, mesh = {Humans ; Consensus ; *Mental Health ; Quality of Life ; *Chromosome Disorders/genetics/psychology ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics ; }, abstract = {Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.}, } @article {pmid37083566, year = {2023}, author = {Bilici, A and Olmez, OF and Kaplan, MA and Oksuzoglu, B and Sezer, A and Karadurmus, N and Cubukcu, E and Sendur, MAN and Aksoy, S and Erdem, D and Basaran, G and Cakar, B and Shbair, ATM and Arslan, C and Sumbul, AT and Sezgin Goksu, S and Karadag, I and Cicin, I and Gumus, M and Selcukbiricik, F and Harputluoglu, H and Demirci, U}, title = {Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {62}, number = {4}, pages = {381-390}, doi = {10.1080/0284186X.2023.2202330}, pmid = {37083566}, issn = {1651-226X}, mesh = {Humans ; Female ; Trastuzumab/therapeutic use ; *Breast Neoplasms/pathology ; Neoadjuvant Therapy/methods ; Docetaxel ; Retrospective Studies ; Receptor, ErbB-2 ; Neoplasm Recurrence, Local/drug therapy/genetics ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.

METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.

RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR.

CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.}, } @article {pmid37082801, year = {2023}, author = {Hacking, SM and Yakirevich, E and Wang, Y}, title = {Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).}, journal = {The journal of pathology. Clinical research}, volume = {9}, number = {4}, pages = {313-321}, pmid = {37082801}, issn = {2056-4538}, mesh = {Humans ; *Triple Negative Breast Neoplasms/genetics/pathology ; Biomarkers, Tumor/analysis ; Tumor Suppressor Protein p53/genetics ; Retinoblastoma Protein/genetics/metabolism ; Retrospective Studies ; *Neuroendocrine Tumors/pathology ; *Carcinoma, Neuroendocrine/pathology ; *Carcinoma, Ductal, Breast ; Cell Differentiation ; RNA, Messenger ; Repressor Proteins ; }, abstract = {Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]). We also identified one separate small cell neuroendocrine carcinoma. Histologic types for these 11 TNBC-NED cases were as follows: 8 invasive ductal carcinoma (IDC) not otherwise specified (NOS), 2 IDC with apocrine features, 1 IDC with solid papillary features. INSM1 had the highest positivity and was seen in all 11 carcinomas. Seven (64%) cases showed p53 aberrant staining, 6 (55%) had Rb protein loss, while 6 (55%) had p53/Rb co-aberrant staining/protein loss. TNBC-NED was associated with Rb protein loss (p < 0.001), as well as p53/Rb co-aberrant staining/protein loss (p < 0.001). In 61 cases negative for NE markers, 37 (61%) showed p53 aberrant staining, while 5 (8%) had Rb protein loss. We also analyzed genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) PanCancer Atlas of 171 basal/TNBC patients. Transcriptomic analysis revealed mRNA expression of RB1 to be correlated negatively with SYN1 mRNA expression (p = 0.0400) and INSM1 mRNA expression (p = 0.0106) in this cohort. We would like to highlight the importance of these findings. TNBC-NED is currently diagnosed as TNBC, and although it overlaps morphologically with TNBC without NED, the unique p53/Rb signature highlights a genetic overlap with NE carcinomas of the breast.}, } @article {pmid37082278, year = {2023}, author = {Pandiar, D and Ramani, P and Krishnan, M and Krishnan, RP}, title = {Intraductal carcinoma of right parapharyngeal space presenting as a fluctuant swelling of retromolar region: Case emphasizing on the histological differential diagnosis.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {27}, number = {Suppl 1}, pages = {S28-S32}, pmid = {37082278}, issn = {0973-029X}, abstract = {Intraductal carcinoma (IDC) of salivary gland is an extremely rare malignancy affecting mainly the parotid glands. Intraoral occurrence is seen mainly on the palate where the tumour arises from the minor salivary glands. No previous case has been described in parapharyngeal space. We report a case of low-grade IDC of the anterior compartment of the right parapharyngeal space that clinically resembled a lesion of vascular origin. Due to the extreme rarity of intraductal carcinoma, it may not be considered by dentists and dental specialists in clinical differential diagnoses, leading to delay in treatment. Intraductal carcinoma must be differentiated from its close histological but high-grade mimickers to avoid unnecessary overtreatment and better patient outcome.}, } @article {pmid37064116, year = {2023}, author = {Yang, G and Zuo, C and Lin, Y and Zhou, X and Wen, P and Zhang, C and Xiao, H and Jiang, M and Fujita, M and Gao, XD and Fu, F}, title = {Comprehensive proteome, phosphoproteome and kinome characterization of luminal A breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1127446}, pmid = {37064116}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer is one of the most frequently occurring malignant cancers worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histological subtypes of breast cancer. In this study, we aimed to deeply explore molecular characteristics and the relationship between IDC and ILC subtypes in luminal A subgroup of breast cancer using comprehensive proteomics and phosphoproteomics analysis.

METHODS: Cancer tissues and noncancerous adjacent tissues (NATs) with the luminal A subtype (ER- and PR-positive, HER2-negative) were obtained from paired IDC and ILC patients respectively. Label-free quantitative proteomics and phosphoproteomics methods were used to detect differential proteins and the phosphorylation status between 10 paired breast cancer and NATs. Then, the difference in protein expression and its phosphorylation between IDC and ILC subtypes were explored. Meanwhile, the activation of kinases and their substrates was also revealed by Kinase-Substrate Enrichment Analysis (KSEA).

RESULTS: In the luminal A breast cancer, a total of 5,044 high-confidence proteins and 3,808 phosphoproteins were identified from 10 paired tissues. The protein phosphorylation level in ILC tissues was higher than that in IDC tissues. Histone H1.10 was significantly increased in IDC but decreased in ILC, Conversely, complement C4-B and Crk-like protein were significantly decreased in IDC but increased in ILC. Moreover, the increased protein expression of Septin-2, Septin-9, Heterogeneous nuclear ribonucleoprotein A1 and Kinectin but reduce of their phosphorylation could clearly distinguish IDC from ILC. In addition, IDC was primarily related to energy metabolism and MAPK pathway, while ILC was more closely involved in the AMPK and p53/p21 pathways. Furthermore, the kinomes in IDC were primarily significantly activated in the CMGC groups.

CONCLUSIONS: Our research provides insights into the molecular characterization of IDC and ILC and contributes to discovering novel targets for further drug development and targeted treatment.}, } @article {pmid37063453, year = {2023}, author = {Zhang, L and Hao, J and Guo, J and Zhao, X and Yin, X}, title = {Predicting of Ki-67 Expression Level Using Diffusion-Weighted and Synthetic Magnetic Resonance Imaging in Invasive Ductal Breast Cancer.}, journal = {The breast journal}, volume = {2023}, number = {}, pages = {6746326}, pmid = {37063453}, issn = {1524-4741}, mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; Retrospective Studies ; *Breast Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; Diffusion Magnetic Resonance Imaging/methods ; ROC Curve ; }, abstract = {OBJECTIVES: To investigate the association between quantitative parameters generated using synthetic magnetic resonance imaging (SyMRI) and diffusion-weighted imaging (DWI) and Ki-67 expression level in patients with invasive ductal breast cancer (IDC).

METHOD: We retrospectively reviewed the records of patients with IDC who underwent SyMRI and DWI before treatment. Precontrast and postcontrast relaxation times (T1, longitudinal; T2, transverse), proton density (PD) parameters, and apparent diffusion coefficient (ADC) values were measured in breast lesions. Univariate and multivariate regression analyses were performed to screen for statistically significant variables to differentiate the high (≥30%) and low (<30%) Ki-67 expression groups. Their performance was evaluated by receiver operating characteristic (ROC) curve analysis.

RESULTS: We analyzed 97 patients. Multivariate regression analysis revealed that the high Ki-67 expression group (n = 57) had significantly higher parameters generated using SyMRI (pre-T1, p=0.001) and lower ADC values (p=0.036) compared with the low Ki-67 expression group (n = 40). Pre-T1 showed the best diagnostic performance for predicting the Ki-67 expression level in patients with invasive ductal breast cancer (areas under the ROC curve (AUC), 0.711; 95% confidence interval (CI), 0.609-0.813).

CONCLUSIONS: Pre-T1 could be used to predict the pretreatment Ki-67 expression level in invasive ductal breast cancer.}, } @article {pmid37061239, year = {2023}, author = {López-Janeiro, Á and Rodriguez, AM and Mendiola, M and Sabbagh, RN and Feliu, J and Villadóniga, A and Mendez, MDC}, title = {Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report.}, journal = {Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia}, volume = {56}, number = {2}, pages = {124-128}, doi = {10.1016/j.patol.2021.05.004}, pmid = {37061239}, issn = {1988-561X}, mesh = {Female ; Humans ; Aged ; *Pancreatic Intraductal Neoplasms ; *Carcinoma, Pancreatic Ductal/pathology ; *Adenocarcinoma, Mucinous/genetics/pathology ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology ; }, abstract = {Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.}, } @article {pmid37060681, year = {2023}, author = {Chamadoira, J and Au, F and Ghai, S and Kulkarni, S and Grant, A and Fleming, R and Alvarenga, P and Freitas, V}, title = {Effects of delayed callback from screening mammography due to the COVID-19 pandemic.}, journal = {Clinical imaging}, volume = {99}, number = {}, pages = {41-46}, pmid = {37060681}, issn = {1873-4499}, mesh = {Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Mammography/methods ; *Breast Neoplasms/diagnostic imaging/epidemiology ; Pandemics ; Retrospective Studies ; Early Detection of Cancer ; *COVID-19/epidemiology ; Mass Screening ; }, abstract = {OBJECTIVE: To determine the frequency and distinguishing imaging characteristics of breast cancers detected on screening mammography which was initially evaluated as a probably benign lesion and the workup was delayed due to the COVID-19 pandemic.

MATERIALS AND METHODS: REB-approved multicenter retrospective screening mammography studies and patient's chart review carried out between February 2020 and March 2020. According to an institutional decision, the frequency and imaging findings deemed probably benign on screening mammography after review by a breast fellowship-trained radiologist with workup deferred until after the first pandemic wave plateau in late July 2020 were recorded. Results were correlated with histopathology if tissue sample performed or an uneventful 2 years follow-up. Descriptive statistical analysis was used to describe the retrieved data set.

RESULTS: Out of 1816 mammography screening between February 2020 and March 2020, 99 women, median age 58 years (range 35-84), 99 mammography had possibly benign findings with workup delayed, and two patients, age 49 and 56, had cancers (2.02%), misinterpreted as benign findings. Both malignant cases were focal asymmetries, with pathology of invasive ductal carcinoma, 12 mm and 9 mm in size. No in-situ carcinoma was detected.

CONCLUSION: The low rate of cancer detected suggests that a delay callback may be a reasonable option for some likely benign findings when immediate callback is not an option, such as during a pandemic. Larger studies would be helpful to support our findings and may allow us to translate the adoption of such a model during potential future pandemic.

CLINICAL RELEVANCE: The results of this study may be helpful for a future situation when delaying a call back from screening mammography is again required.}, } @article {pmid37056337, year = {2023}, author = {Pu, S and Xie, P and Chen, H and Li, Y and He, J and Zhang, H}, title = {Evaluation of outcome of chemotherapy for breast cancer patients older than 70 years: A SEER-based study.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {992573}, pmid = {37056337}, issn = {2234-943X}, abstract = {BACKGROUND: With the aging of the population, the number of elderly breast cancer cases has increased. However, there is a lack of effective randomized clinical trial data to support whether elderly patients should receive chemotherapy. Our goal was to observe the relationship between chemotherapy and breast cancer-specific survival (BCSS) in elderly breast cancer patients and to identify those who could benefit from chemotherapy.

METHODS: We collected the data of patients who were diagnosed with invasive ductal carcinoma and older than 70 years in the SEER database from 1995 to 2016. The independent predictors of BCSS were identified by Cox regression analysis. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to eliminate confounding factors.

RESULTS: A total of 142,537 patients were collected, including 21,782 patients in the chemotherapy group and 120,755 patients in the non-chemotherapy group. We identified the same potential predictors of BCSS after PSM and IPTW, such as age, race, grade, stage, therapy, subtype. A nomogram for predicting 3-year, 5-year and 10-year BCSS was constructed. The 3-year, 5-year and 10-year AUCs of the nomogram were 0.842, 0.819, and 0.788. According to the risk stratification of model predictive scores, patients in the high-risk group achieved the greatest improvement in BCSS after receiving chemotherapy.

CONCLUSIONS: Our study suggests that women older than 70 years with larger tumors, higher grade, positive nodes, negative hormone receptor and inactive local therapy gain prognostic benefits from chemotherapy, but for those with low- and median-risk, conventional chemotherapy should be administered cautiously.}, } @article {pmid37055018, year = {2023}, author = {De Angelis Rigotti, F and Wiedmann, L and Hubert, MO and Vacca, M and Hasan, SS and Moll, I and Carvajal, S and Jiménez, W and Starostecka, M and Billeter, AT and Müller-Stich, B and Wolff, G and Ekim-Üstünel, B and Herzig, S and Fandos-Ramo, C and Krätzner, R and Reich, M and Keitel-Anselmino, V and Heikenwälder, M and Mogler, C and Fischer, A and Rodriguez-Vita, J}, title = {Semaphorin 3C exacerbates liver fibrosis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {78}, number = {4}, pages = {1092-1105}, doi = {10.1097/HEP.0000000000000407}, pmid = {37055018}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.

APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-β-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice.

CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.}, } @article {pmid37042686, year = {2023}, author = {Gallucci, L and Abele, T and Fronza, R and Stolp, B and Laketa, V and Sid Ahmed, S and Flemming, A and Müller, B and Göpfrich, K and Fackler, OT}, title = {Tissue-like environments shape functional interactions of HIV-1 with immature dendritic cells.}, journal = {EMBO reports}, volume = {24}, number = {6}, pages = {e56818}, pmid = {37042686}, issn = {1469-3178}, mesh = {Humans ; *HIV-1 ; Cytokines/metabolism ; Collagen/metabolism ; Antiviral Agents ; Dendritic Cells ; *HIV Infections ; }, abstract = {Immature dendritic cells (iDCs) migrate in microenvironments with distinct cell and extracellular matrix densities in vivo and contribute to HIV-1 dissemination and mounting of antiviral immune responses. Here, we find that, compared to standard 2D suspension cultures, 3D collagen as tissue-like environment alters iDC properties and their response to HIV-1 infection. iDCs adopt an elongated morphology with increased deformability in 3D collagen at unaltered activation, differentiation, cytokine secretion, or responsiveness to LPS. While 3D collagen reduces HIV-1 particle uptake by iDCs, fusion efficiency is increased to elevate productive infection rates due to elevated cell surface exposure of the HIV-1-binding receptor DC-SIGN. In contrast, 3D collagen reduces HIV transfer to CD4 T cells from iDCs. iDC adaptations to 3D collagen include increased pro-inflammatory cytokine production and reduced antiviral gene expression in response to HIV-1 infection. Adhesion to a 2D collagen matrix is sufficient to increase iDC deformability, DC-SIGN exposure, and permissivity to HIV-1 infection. Thus, mechano-physical cues of 2D and 3D tissue-like collagen environments regulate iDC function and shape divergent roles during HIV-1 infection.}, } @article {pmid37038064, year = {2023}, author = {Cerullo, G and Videira-Silva, A and Carrancha, M and Rego, F and Nunes, R}, title = {Complexity of patient care needs in palliative care: a scoping review.}, journal = {Annals of palliative medicine}, volume = {12}, number = {4}, pages = {791-802}, doi = {10.21037/apm-22-894}, pmid = {37038064}, issn = {2224-5839}, mesh = {Humans ; *Quality of Life ; Palliative Care ; *Hospice and Palliative Care Nursing ; Patient Care ; Referral and Consultation ; }, abstract = {BACKGROUND: Recognizing the need for palliative care (PC) and referral to PC teams improves patients' quality of life. However, in patients with moderate/severe clinical complexity, early recognition of the need for PC may not correspond to referral to specialized PC services. The definition for clinical complexity is still underexplored, as well as the instruments available to assess complexity. This scoping review aims to gather relevant information on the definition of clinical complexity in PC, as well as on the instruments used to objectively assess complexity.

METHODS: According to the methodology of a Scoping Review, the keywords: "palliative care", "hospitalization criteria", "complexity criteria", "complexity assessment" and "clinical complexity", were searched in PubMed, Scopus, Cochrane, and b-on databases, during April 2022, for relevant information on the definition and/or approach and/or protocols related to clinical complexity in patients followed in PC, or on the instruments used to assess it, regardless of study design, the language, or year of publication.

RESULTS: From the 626 references found, 15 studies were included in the review. According to these studies, complexity may be organized/defined into 3, 4, or 6 domains, generally including the patient, the family, the health system, and the socio-cultural context. Of the 13 instruments mentioned for the objective assessment of complexity, the HexCom, IDC-Pal, and the recent ID-PALL seem to offer the broadest determinations of complexity.

CONCLUSIONS: Complexity is a dynamic process, which reflects the reality of patients and families, and patients, families, and health professionals' perceptions, and so it must be systematically adjusted to the stage of the disease. The definition of complexity and the development and use of suitable instruments can help to identify, assess, and improve patients' quality of life, while supporting their family across the grieving process. Yet, this may not always be summarized in a quantitative value by easy-to-use instruments, highlighting the role of PC interdisciplinary teams.}, } @article {pmid37035759, year = {2023}, author = {Fan, Z and Wu, S and Sang, H and Li, Q and Cheng, S and Zhu, H}, title = {Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.}, journal = {Mediators of inflammation}, volume = {2023}, number = {}, pages = {9162249}, pmid = {37035759}, issn = {1466-1861}, mesh = {Humans ; *Adenocarcinoma of Lung ; *Lung Neoplasms ; Clinical Relevance ; Disease-Free Survival ; Biomarkers ; Prognosis ; }, abstract = {Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.}, } @article {pmid37032571, year = {2023}, author = {Zemah-Shamir, S and Zemah-Shamir, Z and Peled, Y and Sørensen, OJR and Schwartz Belkin, I and Portman, ME}, title = {Comparing spatial management tools to protect highly migratory shark species in the Eastern Mediterranean Sea hot spots.}, journal = {Journal of environmental management}, volume = {337}, number = {}, pages = {117691}, doi = {10.1016/j.jenvman.2023.117691}, pmid = {37032571}, issn = {1095-8630}, mesh = {Animals ; Humans ; Ecosystem ; *Sharks ; Mediterranean Sea ; Animals, Wild ; *Turtles ; Fisheries ; Conservation of Natural Resources/methods ; Mammals ; }, abstract = {Bycatch of non-target species is a pressing problem for ocean management. It is one of the most concerning issues related to human-wildlife interactions and it affects numerous species including sharks, seabirds, sea turtles, and many critically endangered marine mammals. This paper compares different policy tools for ocean closure management around a unique shark aggregation site in Israel's nearshore coastal waters. We provide a set of recommendations based on an optimal management approach that allows humans to enjoy marine recreational activities such as fishing, while maintaining safe conditions for these apex predators which are vital to the local marine ecosystem. To learn more about recreational fishers' derived benefits, we use a benefit transfer method. Our main conclusion is that dynamic time-area closures offer sustainable and effective management strategies. Since these closures are based on near real-time data, they might successfully preserve specific species in limited areas (i.e., small areas).}, } @article {pmid37029001, year = {2023}, author = {Ramli Hamid, MT and Ab Mumin, N and Wong, YV and Chan, WY and Rozalli, FI and Rahmat, K}, title = {The effectiveness of an ultrafast breast MRI protocol in the differentiation of benign and malignant breast lesions.}, journal = {Clinical radiology}, volume = {78}, number = {6}, pages = {444-450}, doi = {10.1016/j.crad.2023.03.006}, pmid = {37029001}, issn = {1365-229X}, mesh = {Humans ; Adult ; Middle Aged ; Aged ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Contrast Media ; Diagnosis, Differential ; Retrospective Studies ; Magnetic Resonance Imaging/methods ; *Breast Carcinoma In Situ ; *Breast Neoplasms ; }, abstract = {AIM: To evaluate the effectiveness of an ultrafast breast magnetic resonance imaging (MRI) protocol in differentiating benign and malignant breast lesions.

MATERIALS AND METHODS: Fifty-four patients with Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions were recruited between July 2020 to May 2021. A standard breast MRI was performed with the inclusion of the ultrafast protocol between the unenhanced sequence and the first contrast-enhanced sequence. Three radiologists performed image interpretation in consensus. Ultrafast kinetic parameters analysed included the maximum slope (MS), time to enhancement (TTE), and arteriovenous index (AVI). These parameters were compared using receiver operating characteristics with p-values of <0.05 considered to indicate statistical significance.

RESULTS: Eighty-three histopathological proven lesions from 54 patients (mean age 53.87 years, SD 12.34, range 26-78 years) were analysed. Forty-one per cent (n=34) were benign and 59% (n=49) were malignant. All malignant and 38.2% (n=13) benign lesions were visualised on the ultrafast protocol. Of the malignant lesions, 77.6% (n=53) were invasive ductal carcinoma (IDC) and 18.4% (n=9) were ductal carcinoma in situ (DCIS). The MS for malignant lesions (13.27%/s) were significantly larger than for benign (5.45%/s; p<0.0001). No significant differences were seen for TTE and AVI. The area under the ROC curve (AUC) for the MS, TTE, and AVI were 0.836, 0.647, and 0.684, respectively. Different types of invasive carcinoma had similar MS and TTE. The MS of high-grade DCIS was also similar to that of IDC. Lower MS values were observed for low-grade (5.3%/s) compared to high-grade DCIS (14.8%/s) but the results were not significant statistically.

CONCLUSION: The ultrafast protocol showed potential to discriminate between malignant and benign breast lesions with high accuracy using MS.}, } @article {pmid37028455, year = {2023}, author = {Lin, Y and Amkul, K and Laosatit, K and Liu, J and Yimram, T and Chen, J and Yuan, X and Chen, X and Somta, P}, title = {Fine mapping of QTL conferring resistance to calcareous soil in mungbean reveals VrYSL3 as candidate gene for the resistance.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {332}, number = {}, pages = {111698}, doi = {10.1016/j.plantsci.2023.111698}, pmid = {37028455}, issn = {1873-2259}, mesh = {Quantitative Trait Loci/genetics ; *Vigna/genetics/metabolism ; Genome-Wide Association Study ; Soil ; Iron/metabolism ; *Iron Deficiencies ; }, abstract = {Iron is a crucial nutrient for biological functions in plants. High-pH and calcareous soil is a major stress causing iron deficiency chlorosis (IDC) symptoms and yield losses in crops. Use of calcareous soil-tolerance genetic resources is the most effective preventative method to combat the effects of high-pH and calcareous soils. A previous study using a mungbean recombinant inbred line (RIL) population of the cross Kamphaeg Saen 2 (KPS2; IDC susceptible) × NM-10-12 identified a major quantitative trait locus (QTL), qIDC3.1, which controls resistance and explains more than 40% of IDC variation. In this study, we fine-mapped qIDC3.1 and identified an underlying candidate gene. A genome wide association analysis (GWAS) using 162 mungbean accessions identified single nucleotide polymorphisms (SNPs) on chromosome 6; several SNPs were associated with soil plant analysis development (SPAD) values and IDC visual scores of mungbeans planted on calcareous soil, respectively. These SNPs corresponded to qIDC3.1. Using the same RIL population as in the previous study and an advanced backcross population developed from KPS2 and IDC-resistant inbred line RIL82, qIDC3.1 was further confirmed and fine-mapped to an interval of 217 kilobases harboring five predicted genes, including LOC106764181 (VrYSL3), which encodes a yellow stripe1-like-3 (YSL3) protein, YSL3 is involved in iron deficiency resistance. Gene expression analysis revealed that VrYSL3 was highly expressed in mungbean roots. In calcareous soil, expression of VrYSL3 was significantly up-regulated, and it was more obviously upregulated in the roots of RIL82, than in those of KPS2. Sequence comparison of VrYSL3 between the RIL82 and KPS2 revealed four SNPs that result in amino acid changes in the VrYSL3 protein and a 20-bp insertion/deletion in the promoter where a cis-regulatory element resides. Transgenic Arabidopsis thaliana plants overexpressing VrYSL3 showed enhanced iron and zinc contents in the leaves. Taken together, these results indicate that VrYSL3 is a strong candidate gene responsible for calcareous soil resistance in mungbean.}, } @article {pmid37028182, year = {2023}, author = {Yahaya, JJ and Ngaiza, AI and Morgan, ED and Abraham, ZS and Othieno, E}, title = {Invasive ductal carcinoma of breast in a 73-year old male: A rare case report and literature review.}, journal = {International journal of surgery case reports}, volume = {105}, number = {}, pages = {108121}, pmid = {37028182}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Male breast cancers despite being similar to female breast cancers in various aspects; however, they have important distinctive characteristics such as molecular biology, increased tendency for axillary lymph node metastasis and late age at presentation.

PRESENTATION OF CASE: We present the case of a 73-year old indigenous African male who had a 3-year history of right breast swelling which was associated with episodes of pain and tenderness. The assigned clinical stage for the patient was T2aNoMo. The mass was histologically confirmed to be invasive ductal carcinoma, not specified type (NST) without axillary lymph node involvement or distant metastasis. Immunohistochemistry also showed positive results for ER and PR hormonal receptors but negative for HER2.

CLINICAL DISCUSSION: Considering the rarity nature of male breast cancers, this contributes to lack of evidence of the specific treatment approaches despite the noticeable difference in clinical presentation and even biological characteristics of male breast cancers, which are more likely to contribute to poor prognosis.

CONCLUSION: The prevalence of male breast cancers has been reported to be less than 1 % of all male cancers. This contributes to the lack of analytical large studies that address the comprehensive data regarding the clinical outcomes of breast cancer among men and their predictors. Therefore, having prospective multicenter studies in future would help in providing high level of evidence on prognosis.}, } @article {pmid37020090, year = {2023}, author = {Kawaguchi, S and Kinowaki, K and Tamura, N and Masumoto, T and Nishikawa, A and Shibata, A and Tanaka, K and Kobayashi, Y and Ogura, T and Sato, J and Kawabata, H}, title = {High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {637-646}, pmid = {37020090}, issn = {1880-4233}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/pathology ; Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Lymph Nodes/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC.

METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH).

RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively.

CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.}, } @article {pmid37017594, year = {2023}, author = {Zheng, L and Wu, H and Wen, N and Zhang, Y and Wang, Z and Peng, X and Tan, Y and Qiu, L and Qu, F and Tan, W}, title = {Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {15}, pages = {18590-18597}, doi = {10.1021/acsami.2c20846}, pmid = {37017594}, issn = {1944-8252}, mesh = {Humans ; *Cancer Vaccines ; Immunotherapy/methods ; T-Lymphocytes ; Antigens, Neoplasm/genetics ; *Neoplasms/therapy ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Dendritic Cells ; }, abstract = {Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.}, } @article {pmid37015704, year = {2022}, author = {Haq, AU and Li, JP and Khan, I and Agbley, BLY and Ahmad, S and Uddin, MI and Zhou, W and Khan, S and Alam, I}, title = {DEBCM: Deep Learning-Based Enhanced Breast Invasive Ductal Carcinoma Classification Model in IoMT Healthcare Systems.}, journal = {IEEE journal of biomedical and health informatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/JBHI.2022.3228577}, pmid = {37015704}, issn = {2168-2208}, abstract = {Accurate breast cancer (BC) diagnosis is a difficult task that is critical for the proper treatment of BC in IoMT (Internet of Medical Things) healthcare systems. This paper proposes a convolutional neural network (CNN)-based diagnosis method for detecting early-stage breast cancer. In developing the proposed method, we incorporated the CNN model for the invasive ductal carcinoma (IDC) classification using breast histology image data. We have incorporated transfer learning (TL) and data augmentation (DA) mechanisms to improve the CNN model's predictive outcomes. For the fine-tuning process, the CNN model was trained with breast histology image data. Furthermore, the held-out cross-validation method for best model selection and hyper-parameter tuning was incorporated. In addition, various performance evaluation metrics for model performance assessment were computed. The experimental results confirmed that the proposed model outperformed the baseline models across all evaluation metrics, achieving 99.04% accuracy. We recommend the proposed method for early recognition of BC in IoMT healthcare systems due to its high performance.}, } @article {pmid37013774, year = {2023}, author = {Oh, J and Oh, JM and Cho, SY}, title = {METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6}, pages = {2561-2570}, doi = {10.26355/eurrev_202303_31793}, pmid = {37013774}, issn = {2284-0729}, mesh = {Humans ; *Adenocarcinoma of Lung ; Carcinogenesis ; *Colonic Neoplasms ; Down-Regulation ; *Lung Neoplasms/genetics/pathology ; *Methyltransferases/genetics ; *Serine-Arginine Splicing Factors/genetics ; }, abstract = {OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms.

MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression.

RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression.

CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.}, } @article {pmid37011225, year = {2023}, author = {Thomas, R and Umar, T and Borumandi, F}, title = {Intraductal Carcinoma: The Carcinoma In Situ of the Salivary Gland.}, journal = {The Journal of craniofacial surgery}, volume = {34}, number = {5}, pages = {e432-e434}, doi = {10.1097/SCS.0000000000009287}, pmid = {37011225}, issn = {1536-3732}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery ; *Salivary Gland Neoplasms/diagnostic imaging/surgery ; *Carcinoma in Situ ; Biopsy, Fine-Needle ; Parotid Gland/pathology ; *Parotid Neoplasms/diagnostic imaging/surgery ; }, abstract = {Intraductal carcinoma of the salivary gland (IDC) is a rare in situ neoplasm of the salivary gland with similar features to the ductal carcinoma in situ of the breast. This report aims to present the clinical presentation and histological features of IDC. The authors present a 90-year-old gentleman with an indurated and painless tumor within the right parotid. Preoperative diagnostics, including fine needle aspiration cytology, ultrasound scan, and magnetic resonance imaging, were suggestive of Warthin tumor. The tumour was excised by extracapsular dissection. The patient is disease free within the follow-up period of 33 months. Intraductal carcinoma is an indolent phenotype with only a few reported cases with nodal metastases, and to the best of our knowledge, no cases have been reported with distant metastases. Complete surgical excision is recommended to prevent a recurrence. The knowledge of this underreported salivary gland malignancy is important to prevent misdiagnosis and insufficient treatment.}, } @article {pmid37010596, year = {2023}, author = {Danzinger, S and Pöckl, K and Kronawetter, G and Pfeifer, C and Behrendt, S and Gscheidlinger, P and Harrasser, L and Mühlböck, H and Dirschlmayer, W and Schauer, C and Reitsamer, R and Uher, H and Schönau, K and Delmarko, I and Singer, CF}, title = {Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria.}, journal = {Wiener klinische Wochenschrift}, volume = {135}, number = {17-18}, pages = {463-471}, pmid = {37010596}, issn = {1613-7671}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis ; Austria/epidemiology ; *Carcinoma, Ductal, Breast/diagnosis/pathology/surgery ; *Carcinoma, Lobular/diagnosis/pathology/surgery ; Retrospective Studies ; Lymph Nodes/pathology ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register.

METHODS: Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824.

RESULTS: A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC.

CONCLUSION: The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.}, } @article {pmid37010048, year = {2023}, author = {Geitung, JT}, title = {Editorial for "Feasibility of Quantitative MRI using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast".}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {}, number = {}, pages = {}, doi = {10.1002/jmri.28712}, pmid = {37010048}, issn = {1522-2586}, } @article {pmid37008917, year = {2023}, author = {Kender, Z and Jende, JME and Kurz, FT and Tsilingiris, D and Schimpfle, L and Sulaj, A and von Rauchhaupt, E and Bartl, H and Mooshage, C and Göpfert, J and Nawroth, P and Herzig, S and Szendroedi, J and Bendszus, M and Kopf, S}, title = {Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1046690}, pmid = {37008917}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/pathology ; Anisotropy ; Intermediate Filaments ; Sciatic Nerve/diagnostic imaging/pathology ; *Diabetic Neuropathies/complications ; Lower Extremity/diagnostic imaging ; Biomarkers ; }, abstract = {BACKGROUND: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL).

MATERIALS AND METHODS: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage.

RESULTS: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain.

CONCLUSION: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.}, } @article {pmid37006812, year = {2023}, author = {Su, X and Wang, G and Zheng, S and Ge, C and Kong, F and Wang, C}, title = {Comprehensive Explorations of CCL28 in Lung Adenocarcinoma Immunotherapy and Experimental Validation.}, journal = {Journal of inflammation research}, volume = {16}, number = {}, pages = {1325-1342}, pmid = {37006812}, issn = {1178-7031}, abstract = {BACKGROUND: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy.

METHODS: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system.

RESULTS: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration.

CONCLUSION: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.}, } @article {pmid36999966, year = {2023}, author = {Tan, HJ and Tan, PH and Leong, LCH and Tan, VKM and Tan, BKT and Lim, SZ and Preetha, M and Wong, CY and Yong, WS and Sim, Y}, title = {Encapsulated papillary carcinoma of the breast: An institutional case series and literature review.}, journal = {Cancer medicine}, volume = {12}, number = {10}, pages = {11408-11416}, pmid = {36999966}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Papillary/surgery/pathology ; Breast/pathology ; *Carcinoma in Situ ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prognosis ; *Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Encapsulated papillary carcinoma of the breast is rare, making difficult diagnosis and resulting in patients undergoing excision biopsy before definitive surgery. Evidence-based guidelines are sparse. We would like to further elucidate the clinicopathological, treatment and survival outcomes.

MATERIALS AND METHODS: 54 patients identified, with a median follow up duration of 48 months. Patients' demographics, radiological and clinicopathological characteristics, treatment, adjuvant therapies as well as survival data were analysed.

RESULTS: 18 (33.3%) cases were pure EPC, 12 (22.2%) were EPC associated with ductal carcinoma in situ (DCIS) and 24 (44.4%) cases had concurrent invasive ductal carcinoma. EPCs were more likely to present as a solid-cystic mass on sonography (63.8%), regular-shaped (oval or round) (97.9%), lack spiculations (95.7%) and lack suspicious microcalcifications (95.6%). Median tumour size was largest in the EPC with IDC group (18.5 mm). 2 patients developed loco-regional recurrence. Overall survival is good for EPCs of all subtypes.

CONCLUSION: EPC is a rare tumour with excellent prognosis.}, } @article {pmid36993608, year = {2023}, author = {Joshi, U and Budhathoki, P and Gaire, S and Yadav, SK and Shah, A and Adhikari, A and Choong, G and Couzi, R and Giridhar, K and Leon-Ferre, R and Boughey, JC and Hieken, TJ and Mutter, R and Ruddy, KJ and Haddad, TC and Goetz, MP and Couch, FJ and Yadav, S}, title = {Clinical Outcomes and Prognostic Factors in Triple-Negative Invasive Lobular Carcinoma of the Breast.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36993608}, abstract = {Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.}, } @article {pmid36990811, year = {2023}, author = {Hong, F and Li, N and Feng, Z and Zhang, F}, title = {A case of male breast encapsulated papillary carcinoma with ductal carcinoma in situ and invasive ductal carcinoma.}, journal = {Asian journal of surgery}, volume = {46}, number = {9}, pages = {3777-3778}, doi = {10.1016/j.asjsur.2023.03.101}, pmid = {36990811}, issn = {0219-3108}, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Carcinoma, Papillary/pathology ; *Carcinoma, Ductal, Breast/pathology ; Lymphatic Metastasis ; *Breast Neoplasms ; }, } @article {pmid36989828, year = {2023}, author = {Trillo, P and Sandoval, J and Trapani, D and Nicolò, E and Zagami, P and Giugliano, F and Tarantino, P and Vivanet, G and Ascione, L and Friedlaender, A and Esposito, A and Criscitiello, C and Curigliano, G}, title = {Evolution of biological features of invasive lobular breast cancer: Comparison between primary tumour and metastases.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {185}, number = {}, pages = {119-130}, doi = {10.1016/j.ejca.2023.02.028}, pmid = {36989828}, issn = {1879-0852}, mesh = {Humans ; Female ; *Triple Negative Breast Neoplasms ; *Carcinoma, Ductal, Breast/drug therapy ; Retrospective Studies ; *Carcinoma, Lobular/drug therapy ; Receptor, ErbB-2/metabolism ; Neoplasm Recurrence, Local/metabolism ; *Breast Neoplasms/drug therapy ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited.

METHODS: We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications.

RESULTS: Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05).

CONCLUSION: Our results suggest that phenotype switch after metastatic progression may be associated with patients' outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.}, } @article {pmid36976351, year = {2023}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {130}, number = {5}, pages = {687-696}, pmid = {36976351}, issn = {1435-1463}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis/psychology ; Reproducibility of Results ; Cross-Sectional Studies ; Feasibility Studies ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Language ; }, abstract = {BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients.

METHODS: N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33).

RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach.

DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.}, } @article {pmid36974780, year = {2023}, author = {Buonomo, OC and Pellicciaro, M and Materazzo, M and Berardi, S and Gigliotti, PE and Caspi, J and Meucci, R and Perretta, T and Portarena, I and Dauri, M and Pistolese, CA and Vanni, G}, title = {Surgical Treatments for Ductal Carcinoma In Situ (DCIS) in Elderly Patients.}, journal = {Anticancer research}, volume = {43}, number = {4}, pages = {1555-1562}, doi = {10.21873/anticanres.16305}, pmid = {36974780}, issn = {1791-7530}, mesh = {Humans ; Female ; Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Lymphatic Metastasis ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {BACKGROUND/AIM: Despite an aging population, there is no consensus regarding ductal carcinoma in situ (DCIS) treatment for elderly women. Breast surgery can be well tolerated even in elderly patients. The aim of this study is to evaluate the surgical management of DCIS in elderly patients.

PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS from 2016 to 2022 at our Breast Unit and divided our population according to age.

RESULTS: Out of 231 patients with DCIS, 45 (19.5%) were elderly. The Charlson comorbidity index and American Society of Anesthesiology (ASA) score was significantly higher in the elderly (p<0.001 for both). Among the elderly, 10 (22.2%) patients received upstaging diagnoses, versus 18 (9.7%) in the control (p=0.048). Twelve (26.7%) of the elderly patients underwent sentinel lymph node biopsy, versus 93 (50%) in the control group (p=0.005). No difference was reported between groups in terms of breast conserving surgeries performed. A higher incidence of surgeries performed using local anesthesia was reported in the elderly group (p=0.041). Thirty-day surgical complications, according to Clavien-Dindo, did not show significant differences.

CONCLUSION: Despite higher comorbidity and ASA score, breast surgery is safe and feasible in elderly patients. Due to the higher risk of upstaging to invasive ductal carcinoma, surgery should be performed but sentinel lymph node biopsy should be omitted, owing to the low risk of lymph node metastasis and lower use of adjuvant treatments.}, } @article {pmid36973739, year = {2023}, author = {Cheng, X and Jia, X and Wang, C and Zhou, S and Chen, J and Chen, L and Chen, J}, title = {Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {112}, pmid = {36973739}, issn = {1477-7819}, support = {2021Y29//Medical science and technology program in Ningbo/ ; }, mesh = {Female ; Humans ; Phosphofructokinase-2/genetics/metabolism ; Cell Proliferation ; Cell Line, Tumor ; *MicroRNAs/genetics ; *Hyperglycemia/complications/genetics ; Phenotype ; *Carcinoma, Ductal/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; }, abstract = {BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.

METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.

RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.

CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.}, } @article {pmid36973678, year = {2023}, author = {Tong, S and Jiang, N and Wan, JH and Chen, CR and Wang, SH and Wu, CY and Guo, Q and Xiao, XY and Huang, H and Zhou, T}, title = {The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {275}, pmid = {36973678}, issn = {1471-2407}, mesh = {Humans ; Cyclin D1 ; Prognosis ; *Lung Neoplasms/pathology ; *Adenocarcinoma of Lung/genetics ; Biomarkers, Tumor/genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.

METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.

RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.

CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.}, } @article {pmid36970720, year = {2022}, author = {Glencer, AC and Miller, PN and Greenwood, H and Maldonado Rodas, CK and Freimanis, R and Basu, A and Mukhtar, RA and Brabham, C and Kim, P and Hwang, ES and Rosenbluth, JM and Hirst, GL and Campbell, MJ and Borowsky, AD and Esserman, LJ}, title = {Identifying Good Candidates for Active Surveillance of Ductal Carcinoma In Situ: Insights from a Large Neoadjuvant Endocrine Therapy Cohort.}, journal = {Cancer research communications}, volume = {2}, number = {12}, pages = {1579-1589}, pmid = {36970720}, issn = {2767-9764}, support = {U01 CA111234/CA/NCI NIH HHS/United States ; U01 CA196406/CA/NCI NIH HHS/United States ; T32 CA251070/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Watchful Waiting ; *Breast Neoplasms/diagnostic imaging ; }, abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment. This was an observational study that enrolled patients with DCIS who chose not to pursue surgical resection from 2002 to 2019 at a single academic medical center. All patients underwent breast MRI exams at 3- to 6-month intervals. Patients with hormone receptor-positive disease received endocrine therapy. Surgical resection was strongly recommended if clinical or radiographic evidence of disease progression developed. A recursive partitioning (R-PART) algorithm incorporating breast MRI features and endocrine responsiveness was used retrospectively to stratify risk of IDC. A total of 71 patients were enrolled, 2 with bilateral DCIS (73 lesions). A total of 34 (46.6%) were premenopausal, 68 (93.2%) were hormone-receptor positive, and 60 (82.1%) were intermediate- or high-grade lesions. Mean follow-up time was 8.5 years. Over half (52.1%) remained on active surveillance without evidence of IDC with mean duration of 7.4 years. Twenty patients developed IDC, of which 6 were HER2 positive. DCIS and subsequent IDC had highly concordant tumor biology. Risk of IDC was characterized by MRI features after 6 months of endocrine therapy exposure; low-, intermediate-, and high-risk groups were identified with respective IDC rates of 8.7%, 20.0%, and 68.2%. Thus, active surveillance consisting of neoadjuvant endocrine therapy and serial breast MRI may be an effective tool to risk-stratify patients with DCIS and optimally select medical or surgical management.

SIGNIFICANCE: A retrospective analysis of 71 patients with DCIS who did not undergo upfront surgery demonstrated that breast MRI features after short-term exposure to endocrine therapy identify those at high (68.2%), intermediate (20.0%), and low risk (8.7%) of IDC. With 7.4 years mean follow-up, 52.1% of patients remain on active surveillance. A period of active surveillance offers the opportunity to risk-stratify DCIS lesions and guide decisions for operative management.}, } @article {pmid36970436, year = {2023}, author = {Yoshida, K and Kotsuma, T and Takaoka, Y and Tamenaga, S and Yamazaki, H and Nose, T and Murakami, N and Inaba, K and Akiyama, H and Masui, K and Takenaka, T and Kubota, H and Tselis, N and Masuda, N and Yasojima, H and Takeda, M and Mano, M and Nakamura, S and Utsunomiya, K and Tanigawa, N and Tanaka, E}, title = {HDR-brachytherapy for accelerated partial breast irradiation: Long-term experience from a Japanese institution.}, journal = {Journal of contemporary brachytherapy}, volume = {15}, number = {1}, pages = {1-8}, pmid = {36970436}, issn = {1689-832X}, abstract = {PURPOSE: We investigated the long-term oncological outcome of high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIB) for adjuvant accelerated partial breast irradiation (APBI) after breast conserving surgery in Japanese patients.

MATERIAL AND METHODS: Between June 2002 and October 2011, 86 breast cancer patients were treated at National Hospital Organization Osaka National Hospital (trial number of the local institutional review board, 0329). Median age was 48 years (range, 26-73 years). Eighty patients had invasive and 6 patients non-invasive ductal carcinoma. Tumor stage distribution was pT0 in 2, pTis in 6, pT1 in 55, pT2 in 22, and pT3 in one patient, respectively. Twenty-seven patients had close/positive resection margins. Total physical HDR dose was 36-42 Gy in 6-7 fractions.

RESULTS: At a median follow-up of 119 months (range, 13-189 months), the 10-year local control (LC) and overall survival rate was 93% and 88%, respectively. Concerning the 2009 Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology risk stratification scheme, the 10-year LC rate was 100%, 100%, and 91% for patients considered as low-risk, intermediate-risk, and high-risk, respectively. According to the 2018 American Brachytherapy Society risk stratification scheme, the 10-year LC rate was 100% and 90% for patients 'acceptable' and 'unacceptable' for APBI, respectively. Wound complications were observed in 7 patients (8%). Risk factors for wound complications were the omission of prophylactic antibiotics during MIB, open cavity implantation, and V100 ≥ 190 cc. No grade ≥ 3 late complications (CTCVE version 4.0) were observed.

CONCLUSIONS: Adjuvant APBI using MIB is associated with favorable long-term oncological outcomes in Japanese patients for low-risk, intermediate-risk, and acceptable groups of patients.}, } @article {pmid36969041, year = {2023}, author = {Xu, J and Xu, Y and Xu, C and Wang, C}, title = {Morphological and molecular pathological features of the breast carcinoma with choriocarcinomatous features: A case report and a literature review.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {984425}, pmid = {36969041}, issn = {2234-943X}, abstract = {Here we present a rare case of breast cancer with both invasive ductal carcinoma and choriocarcinoma components in a 55-year-old woman. Firstly, the serum human chorionic gonadotropin level showed 15.9mIU/ml preoperatively. And adequate immunohistochemical tests were performed on the specimen. Secondly, High-throughput sequencing was performed to detect the molecular characteristics of the two components, respectively. Then, DNA short tandem repeat (STR) analysis confirmed the homology of the two components, indicating the somatic origin of choriocarcinoma components. Finally, the clinical course and pathological characteristics of the case were reviewed and a literature search for other cases was performed.}, } @article {pmid36959807, year = {2023}, author = {Huang, Q and Nong, W and Tang, X and Gao, Y}, title = {An ultrasound-based radiomics model to distinguish between sclerosing adenosis and invasive ductal carcinoma.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1090617}, pmid = {36959807}, issn = {2234-943X}, abstract = {OBJECTIVES: We aimed to develop an ultrasound-based radiomics model to distinguish between sclerosing adenosis (SA) and invasive ductal carcinoma (IDC) to avoid misdiagnosis and unnecessary biopsies.

METHODS: From January 2020 to March 2022, 345 cases of SA or IDC that were pathologically confirmed were included in the study. All participants underwent pre-surgical ultrasound (US), from which clinical information and ultrasound images were collected. The patients from the study population were randomly divided into a training cohort (n = 208) and a validation cohort (n = 137). The US images were imported into MaZda software (Version 4.2.6.0) to delineate the region of interest (ROI) and extract features. Intragroup correlation coefficient (ICC) was used to evaluate the consistency of the extracted features. The least absolute shrinkage and selection operator (LASSO) logistic regression and cross-validation were performed to obtain the radiomics score of the features. Based on univariate and multivariate logistic regression analyses, a model was developed. 56 cases from April 2022 to December 2022 were included for independent validation of the model. The diagnostic performance of the model and the radiomics scores were evaluated by performing the receiver operating characteristic (ROC) analysis. The calibration curve and decision curve analysis (DCA) were used for calibration and evaluation. Leave-One-Out Cross-Validation (LOOCV) was used for the stability of the model.

RESULTS: Three predictors were selected to develop the model, including radiomics score, palpable mass and BI-RADS. In the training cohort, validation cohort and independent validation cohort, AUC of the model and radiomics score were 0.978 and 0.907, 0.946 and 0.886, 0.951 and 0.779, respectively. The model showed a statistically significant difference compared with the radiomics score (p<0.05). The Kappa value of the model was 0.79 based on LOOCV. The Brier score, calibration curve, and DCA showed the model had a good calibration and clinical usefulness.

CONCLUSIONS: The model based on radiomics, ultrasonic features, and clinical manifestations can be used to distinguish SA from IDC, which showed good stability and diagnostic performance. The model can be considered a potential candidate diagnostic tool for breast lesions and can contribute to effective clinical diagnosis.}, } @article {pmid36952359, year = {2023}, author = {Wang, DY and Li, SF and Gao, SL and Yuan, P and Zhang, BL}, title = {Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population-based study from China.}, journal = {Cancer medicine}, volume = {12}, number = {8}, pages = {9644-9649}, pmid = {36952359}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/diagnosis/epidemiology/therapy ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Prognosis ; China/epidemiology ; *Carcinoma, Neuroendocrine/diagnosis/epidemiology/therapy ; }, abstract = {AIM: We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast.

METHODS: All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC.

RESULTS: After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR = 2.94, 95% CI: 1.69-5.12, p < 0.001).

CONCLUSION: NEC patients have a worse disease-free survival than IDC patients.}, } @article {pmid36951614, year = {2023}, author = {Amano, M and Fujita, S and Takei, N and Sano, K and Wada, A and Sato, K and Kikuta, J and Kuwatsuru, Y and Tachibana, R and Sekine, T and Horimoto, Y and Aoki, S}, title = {Feasibility of Quantitative MRI Using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {}, number = {}, pages = {}, doi = {10.1002/jmri.28683}, pmid = {36951614}, issn = {1522-2586}, support = {JP20K08035//JSPS KAKENHI/ ; //the Juntendo Research Branding Project/ ; }, abstract = {BACKGROUND: Two-dimensional synthetic MRI of the breast has limited spatial coverage. Three-dimensional (3D) synthetic MRI could provide volumetric quantitative parameters that may reflect the immunohistochemical (IHC) status in invasive ductal carcinoma (IDC) of the breast.

PURPOSE: To evaluate the feasibility of 3D synthetic MRI using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (QALAS) for discriminating the IHC status, including hormone receptor (HR), human epidermal growth factor receptor 2 (HER 2), and Ki-67 expression in IDC.

STUDY TYPE: Prospective observational study.

POPULATION: A total of 33 females with IDC of the breast (mean, 52.3 years).

FIELD STRENGTH/SEQUENCE: A 3-T, 3D-QALAS gradient-echo and fat-suppressed T1-weighted 3D fast spoiled gradient-echo sequences.

ASSESSMENT: Two radiologists semiautomatically delineated 3D regions of interest (ROIs) of the whole tumors on the dynamic MRI that was registered to the synthetic T1-weighted images acquired from 3D-QALAS. The mean T1 and T2 were measured for each IDC.

STATISTICAL TESTS: Intraclass correlation coefficient for assessing interobserver agreement. Mann-Whitney U test to determine the relationship between the mean T1 or T2 and the IHC status. Multivariate logistic regression analysis followed by receiver operating characteristics (ROC) analysis for discriminating IHC status. A P value <0.05 was considered statistically significant.

RESULTS: The interobserver agreement was good to excellent. There was a significant difference in the mean T1 between HR-positive and HR-negative lesions, while the mean T2 value differed between HR-positive and HR-negative lesions, between the triple-negative and HR-positive or HER2-positive lesions, and between the Ki-67 level > 14% and ≤ 14%. Multivariate analysis showed that the mean T2 was higher in HR-negative IDC than in HR-positive IDC. ROC analysis revealed that the mean T2 was predictive for discriminating HR status, triple-negative status, and Ki-67 level.

DATA CONCLUSION: 3D synthetic MRI using QALAS may be useful for discriminating IHC status in IDC of the breast.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36949078, year = {2023}, author = {Gorman, C and Punzo, D and Octaviano, I and Pieper, S and Longabaugh, WJR and Clunie, DA and Kikinis, R and Fedorov, AY and Herrmann, MD}, title = {Interoperable slide microscopy viewer and annotation tool for imaging data science and computational pathology.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1572}, pmid = {36949078}, issn = {2041-1723}, support = {HHSN2612015000031//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; *Microscopy/methods ; *Data Science ; Reproducibility of Results ; }, abstract = {The exchange of large and complex slide microscopy imaging data in biomedical research and pathology practice is impeded by a lack of data standardization and interoperability, which is detrimental to the reproducibility of scientific findings and clinical integration of technological innovations. We introduce Slim, an open-source, web-based slide microscopy viewer that implements the internationally accepted Digital Imaging and Communications in Medicine (DICOM) standard to achieve interoperability with a multitude of existing medical imaging systems. We showcase the capabilities of Slim as the slide microscopy viewer of the NCI Imaging Data Commons and demonstrate how the viewer enables interactive visualization of traditional brightfield microscopy and highly-multiplexed immunofluorescence microscopy images from The Cancer Genome Atlas and Human Tissue Atlas Network, respectively, using standard DICOMweb services. We further show how Slim enables the collection of standardized image annotations for the development or validation of machine learning models and the visual interpretation of model inference results in the form of segmentation masks, spatial heat maps, or image-derived measurements.}, } @article {pmid36939947, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Correction to: Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {7}, pages = {2631}, doi = {10.1007/s10072-023-06746-4}, pmid = {36939947}, issn = {1590-3478}, } @article {pmid36939123, year = {2023}, author = {Mareti, E and Vavoulidis, E and Papanastasiou, A and Maretis, T and Tsampazis, N and Margioula-Siarkou, C and Chatzinikolaou, F and Giasari, S and Nasioutziki, M and Daniilidis, A and Zepiridis, L and Dinas, K}, title = {Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.}, journal = {Diagnostic cytopathology}, volume = {51}, number = {7}, pages = {414-422}, doi = {10.1002/dc.25130}, pmid = {36939123}, issn = {1097-0339}, mesh = {Humans ; Female ; Biopsy, Fine-Needle ; Real-Time Polymerase Chain Reaction ; Human Papillomavirus Viruses ; Greece/epidemiology ; *Papillomavirus Infections ; *Breast Neoplasms/pathology ; Carcinogenesis ; Papillomaviridae/genetics ; }, abstract = {BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.

METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.

RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.

CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.}, } @article {pmid36937402, year = {2023}, author = {Zheng, C and Fu, C and Wen, Y and Liu, J and Lin, S and Han, H and Han, Z and Xu, C}, title = {Clinical characteristics and overall survival prognostic nomogram for metaplastic breast cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1030124}, pmid = {36937402}, issn = {2234-943X}, abstract = {BACKGROUND: Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC.

METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA).

RESULTS: MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram's C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model's (0.700 95% CI 0.644 -0.756). Nomogram's great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869).

CONCLUSIONS: Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses.}, } @article {pmid36934657, year = {2023}, author = {Varun, K and Zoltan, K and Alba, S and Manuel, B and Elisabeth, K and Dimitrios, T and Jan B, G and Maik, B and Khurrum, S and Berend, I and Stephen, H and Thomas, F and Julia, S and Peter, N and Stefan, K}, title = {Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104516}, pmid = {36934657}, issn = {2352-3964}, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Interleukin-6 ; *Prediabetic State ; Albuminuria/complications ; Cross-Sectional Studies ; Prospective Studies ; *Lung Diseases ; Fibrosis ; DNA Damage ; Cellular Senescence ; }, abstract = {BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.

METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years.

FINDINGS: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression.

INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis.

FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).}, } @article {pmid36933533, year = {2023}, author = {Tahir, N and Zahid, M and Jillani, A and Tahir, S and Yaseen, M and Abbas, Q and Abdul Shakoor, R and Hussain, SZ and Shahid, I}, title = {Impact of alternate Mn doping in ternary nanocomposites on their structural, optical and antimicrobial properties: Comparative analysis of photocatalytic degradation and antibacterial activity.}, journal = {Journal of environmental management}, volume = {337}, number = {}, pages = {117706}, doi = {10.1016/j.jenvman.2023.117706}, pmid = {36933533}, issn = {1095-8630}, mesh = {*Molybdenum ; Light ; Anti-Bacterial Agents/pharmacology ; Sunlight ; *Nanocomposites/chemistry ; Catalysis ; }, abstract = {The present study was done to investigate and compare the photocatalytic and antibacterial activity of two in situ Manganese doped ternary nanocomposites. The dual ternary hybrid systems comprised Mn-doped Ag2WO4 coupled with MoS2-GO and Mn-doped MoS2 coupled with Ag2WO4-GO. Both hierarchical alternate Mn-doped ternary heterojunctions formed efficient plasmonic catalysts for wastewater treatment. The novel nanocomposites were well-characterized using XRD, FTIR, SEM-EDS, HR-TEM, XPS, UV-VIS DRS, and PL techniques confirming the successful insertion of Mn[+2] ions in respective host substrates. The bandgap of the ternary nanocomposites evaluated by the tauc plot showed them visible light-active nanocomposites. The photocatalytic ability of both Mn-doped coupled nanocomposites was investigated against the dye methylene blue. Both ternary nanocomposites showed excellent sunlight harvesting ability for dye degradation in 60 min. The maximum catalytic efficiency of both photocatalysts was obtained at a solution pH value of 8, photocatalyst dose and oxidant dose of 30 mg/100 mL and 1 mM for Mn-Ag2WO4/MoS2-GO, 50 mg/100 mL, 3 mM for Mn-MoS2/Ag2WO4-GO keeping IDC of 10 ppm for all photocatalysts. The nanocomposites showed excellent photocatalytic stability after five successive cycles. The response surface methodology was used as a statistical tool for the evaluation of the photocatalytic response of several interacting parameters for dye degradation by ternary composites. The antibacterial activity was determined by the inactivation of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria by support-based doped ternary hybrids.}, } @article {pmid36933394, year = {2023}, author = {Vormittag-Nocito, E and Acosta, AM and Agarwal, S and Narayan, KD and Kumar, R and Al Rasheed, MRH and Kajdacsy-Balla, A and Behm, FG and Mohapatra, G}, title = {In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {6}, pages = {100130}, doi = {10.1016/j.modpat.2023.100130}, pmid = {36933394}, issn = {1530-0285}, mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/genetics/pathology ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostatectomy ; }, abstract = {Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.}, } @article {pmid36932870, year = {2023}, author = {Rastin, M and Mahmoudi, M and Tabasi, N and Kia, N and Hajavi, J and Esmaeili, SA}, title = {The Evaluation of the Effect of Tolerogenic Probiotics on the Maturation of Healthy Dendritic Cells versus Immature Dendritic Cells.}, journal = {Iranian journal of immunology : IJI}, volume = {20}, number = {1}, pages = {26-35}, doi = {10.22034/iji.2023.91783.2131}, pmid = {36932870}, issn = {1735-367X}, mesh = {*Interleukin-10 ; Cell Differentiation ; Cells, Cultured ; Interleukin-12 ; Dendritic Cells ; *Probiotics ; }, abstract = {BACKGROUND: Dendritic cells, (DCs) as one of the important immune cell populations, are responsible for the initiation, development, and control of acquired immune responses. Myeloid dendritic cells can be used as a vaccine for several autoimmune diseases and cancers. Tolerogenic probiotics with regulatory properties can affect the maturation and development of immature dendritic cells (IDC) into mature DCs with certain immunomodulatory effects.

OBJECTIVE: To assess the immunomodulatory effect of Lactobacillus rhamnosus and Lactobacillus delbrueckii, as two tolerogenic probiotics, in the differentiation and maturation of myeloid dendritic cells.

METHODS: The IDCs were derived from the healthy donors in GM-CSF and IL 4 medium. Mature DCs (MDC) were produced with L. delbrueckii, L. rhamnosus, and LPS from IDCs. Real-Time PCR and flow cytometry were used to confirm the DC maturation and to determine DC markers as well as IDO, IL10, and IL12 expression levels, respectively.

RESULTS: Probiotic-derived DCs showed a significant reduction in the level of HLA-DR (P≤0.05), CD86 (P≤0.05), CD80 (P≤0.001), CD83 (P≤0.001), and CD1a. Also, the expression of IDO (P≤0.001) and IL10 increased while IL12 expression decreased (P≤0.001).

CONCLUSION: Our findings revealed that tolerogenic probiotics could induce regulatory DCs by reducing co-stimulatory molecules along with increasing the expression of IDO and IL10 during the differentiation process. Therefore, the induced regulatory DCs probably can be used in the treatment of various inflammatory diseases.}, } @article {pmid36931261, year = {2023}, author = {Cardona Barberán, A and Bonte, D and Boel, A and Thys, V and Paredis, R and Machtelinckx, F and De Sutter, P and De Croo, I and Leybaert, L and Stoop, D and Coucke, P and Vanden Meerschaut, F and Heindryckx, B}, title = {Assisted oocyte activation does not overcome recurrent embryo developmental problems.}, journal = {Human reproduction (Oxford, England)}, volume = {38}, number = {5}, pages = {872-885}, doi = {10.1093/humrep/dead051}, pmid = {36931261}, issn = {1460-2350}, mesh = {Pregnancy ; Child ; Humans ; Male ; Female ; Animals ; Mice ; *Sperm Injections, Intracytoplasmic/methods ; *Calcium ; Ionomycin ; Calcimycin ; Prospective Studies ; Semen ; Pregnancy Rate ; Oocytes ; Embryonic Development ; Retrospective Studies ; Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; }, abstract = {STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?

SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.

WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.

STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (≥60%) but impaired embryonic development (≤15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.

Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.

We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value = 0.06); 9.35% (30/321, P-value = 0.18), 25.00% (11/44, P-value = 0.75), and 15.91% (7/44, P-value = 0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.

Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.

Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.

This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.

TRIAL REGISTRATION NUMBER: NCT03354013.}, } @article {pmid36927911, year = {2023}, author = {Mitsuyoshi, A and Yanagawa, T and Kikumori, K and Hori, A and Oshima, K and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {3}, pages = {366-368}, pmid = {36927911}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; Peritoneum ; *Breast Neoplasms/surgery/pathology ; Positron Emission Tomography Computed Tomography ; Umbilicus/surgery/pathology ; *Carcinoma, Ductal ; }, abstract = {The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.}, } @article {pmid36927901, year = {2023}, author = {Miyazaki, S and Iwasaki, K and Narita, T and Yoneda, G and Takei, H and Jibiki, N}, title = {[A Case of Bilateral HER2-Positive Invasive Ductal Carcinoma with Complete Response on One Side with Trastuzumab Deruxtecan].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {3}, pages = {327-331}, pmid = {36927901}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Receptor, ErbB-2 ; Mastectomy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Recurrence, Local/surgery ; Trastuzumab ; *Carcinoma, Ductal/drug therapy ; }, abstract = {A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy. After this treatment the right breast cancer, right axillary LN metastasis, and bilateral pulmonary metastases contracted, while the left breast cancer and left axillary LN metastasis expanded. Trastuzumab emtansine was then administered, and the left axillary LN metastasis contracted, however, the left breast cancer expanded, resulting in marked breast engorgement. When trastuzumab deruxtecan(T-DXd)was administered, the left breast cancer contracted for the first time during the overall treatment process, and the signs of breast inflammation disappeared. Other lesions showed no recrudescence. T-DXd was administered seven times, and, at the stage of maximum contraction during the treatment period, a total left mastectomy and left axillary LN dissection were performed. Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.}, } @article {pmid36927792, year = {2023}, author = {Onkar, S and Cui, J and Zou, J and Cardello, C and Cillo, AR and Uddin, MR and Sagan, A and Joy, M and Osmanbeyoglu, HU and Pogue-Geile, KL and McAuliffe, PF and Lucas, PC and Tseng, GC and Lee, AV and Bruno, TC and Oesterreich, S and Vignali, DAA}, title = {Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment.}, journal = {Nature cancer}, volume = {4}, number = {4}, pages = {516-534}, pmid = {36927792}, issn = {2662-1347}, support = {R35 GM146989/GM/NIGMS NIH HHS/United States ; }, mesh = {Female ; Humans ; *Carcinoma, Lobular/drug therapy ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; Treatment Outcome ; Disease-Free Survival ; Tumor Microenvironment ; }, abstract = {T cell-centric immunotherapies have shown modest clinical benefit thus far for estrogen receptor-positive (ER[+]) breast cancer. Despite accounting for 70% of all breast cancers, relatively little is known about the immunobiology of ER[+] breast cancer in women with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). To investigate this, we performed phenotypic, transcriptional and functional analyses for a cohort of treatment-naive IDC (n = 94) and ILC (n = 87) tumors. We show that macrophages, and not T cells, are the predominant immune cells infiltrating the tumor bed and the most transcriptionally diverse cell subset between IDC and ILC. Analysis of cellular neighborhoods revealed an interplay between macrophages and T cells associated with longer disease-free survival in IDC but not ILC. Our datasets provide a rich resource for further interrogation into immune cell dynamics in ER[+] IDC and ILC and highlight macrophages as a potential target for ER[+] breast cancer.}, } @article {pmid36926632, year = {2023}, author = {Tower, A and Hughes, J and Moore, L and Srivastava, K}, title = {Mixed metaplastic carcinoma of the breast: a case report.}, journal = {Journal of surgical case reports}, volume = {2023}, number = {3}, pages = {rjad144}, pmid = {36926632}, issn = {2042-8812}, abstract = {A 68 year-old woman with no significant medical history discovered a lump incidentally in her left breast. The patient's initial imaging revealed a 4.6-cm irregular mass at 11:00 categorized as a BI-RADS 5 as well as an enlarged axillary lymph node and an area of 2.5 cm of heterogeneous calcifications in the 3 o'clock position. The 4.6-cm lesion was revealed to be infiltrating ductal carcinoma with a squamous component, mixed metaplastic carcinoma, which was strongly ER (100+)/PR (100+) positive, HER-2/Neu negative on FISH. The 2.5-cm calcifications were ductal carcinoma in situ. The patient completed neoadjuvant chemotherapy, and had an excellent response. After further discussion, the patient elected for breast conservation therapy and underwent a left wireless localized partial mastectomy with a left axillary dissection. Surgical pathology revealed a near complete pathologic response with only 8-mm residual tumour as well as a negative conversion of the clipped axillary node.}, } @article {pmid36926394, year = {2023}, author = {Wang, YJ and Huang, CP and Hong, ZJ and Liao, GS and Yu, JC}, title = {Invasive breast carcinoma with osteoclast-like stromal giant cells: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {7}, pages = {1521-1527}, pmid = {36926394}, issn = {2307-8960}, abstract = {BACKGROUND: Invasive breast carcinoma with osteoclast-like stromal giant cells (OGCs) is an extremely rare morphology of breast carcinomas. To the best of our knowledge, the most recent case report describing this rare pathology was published six years ago. The mechanism controlling the development of this unique histological formation is still unknown. Further, the prognosis of patients with OGC involvement is also controversial.

CASE SUMMARY: We report the case of a 48-year-old woman, who presented to the outpatient department with a palpable, growing, painless mass in her left breast for about one year. Sonography and mammography revealed a 26.5 mm × 18.8 mm asymmetric, lobular mass with circumscribed margin and the Breast Imaging Reporting and Data System was category 4C. Sono-guided aspiration biopsy revealed invasive ductal carcinoma. The patient underwent breast conserving surgery and was diagnosed with invasive breast carcinoma with OGCs, grade II, with intermediate grade of ductal carcinoma in situ (ER: 80%, 3+, PR: 80%, 3+, HER-2: negative, Ki 67: 30%). Adjuvant chemotherapy and post-operation radiotherapy were initiated thereafter.

CONCLUSION: As a rare morphology of breast cancer, breast carcinoma with OGC occurs most often in relatively young women, has less lymph node involvement, and its occurrence is not race-dependent.}, } @article {pmid36926252, year = {2023}, author = {Song, G and Zhang, Y}, title = {Clinicopathological characteristics, treatments, and prognosis of breast ductal carcinoma in situ with microinvasion: A narrative review.}, journal = {Chronic diseases and translational medicine}, volume = {9}, number = {1}, pages = {5-13}, pmid = {36926252}, issn = {2589-0514}, abstract = {BACKGROUND: Ductal carcinoma in situ with microinvasion (DCIS-MI) is defined as ductal carcinoma in situ (DCIS) with a microscopic invasive focus ≤1 mm in the longest diameter. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, treatment, and prognosis of it.

METHODS: Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word: breast cancer, microinvasion, DCIS, DCIS-MI, and invasive ductal carcinoma (IDC).

RESULTS: DCIS-MI tends to express more aggressive pathological features such as necrosis, HER2+, ER- or PR-, and high nuclear grade. The overall prognosis of DCIS-MI is typically good, however, some indicators such as young age, HR-, HER2+ and multimicroinvasive lesions, were associated with worse prognoses. And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC. Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR- orHER2+ to improve the prognosis.

CONCLUSION: DCIS-MI has more aggressive pathological features, which may suggest its biological behavior is worse than that of DCIS and similar to early IDC. Although the overall prognosis of DCIS-MI is good, when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status, HER2 expression and axillary lymph node status of patients, because these may affect the prognosis and treatment response.}, } @article {pmid36923390, year = {2023}, author = {Surabhi, DM and Wilson, JC and Singh, M and Green, L}, title = {Recognizing invasive breast carcinoma of no special type with medullary pattern.}, journal = {Radiology case reports}, volume = {18}, number = {5}, pages = {1788-1792}, pmid = {36923390}, issn = {1930-0433}, abstract = {Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is an uncommon histologic type of invasive breast carcinoma. It is associated with high-grade, poorly differentiated tumor cells that form large sheets of irregular confluent tumor cells associated with a prominent lymphocytic infiltrate. Patients with IBC-NST with medullary pattern are often postmenopausal women with a high body mass index and multiparity. We report the case of a 71-year-old woman who presented for routine screening mammography and breast mass suspicious for malignancy, initially thought to be invasive ductal carcinoma with an associated prominent lymphoid infiltrate. However, it was ultimately diagnosed as IBC-NST with medullary pattern, and radiologic imaging (particularly ultrasound and mammography) along with pathology review were critical in making the diagnosis. We make the case of the importance of radiographic imaging in diagnosing this condition, as the prognosis of IBC-NST with medullary pattern is typically more favorable compared to IBC-NST.}, } @article {pmid36914070, year = {2023}, author = {Tholany, J and Suzuki, H and Livorsi, DJ and Perencevich, EN and Goto, M}, title = {The association of infectious diseases consultation and 30-day mortality rates among veterans with enterococcal bacteraemia: a propensity score-matched retrospective cohort study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {8}, pages = {1039-1044}, doi = {10.1016/j.cmi.2023.03.009}, pmid = {36914070}, issn = {1469-0691}, mesh = {Humans ; Vancomycin ; Retrospective Studies ; Propensity Score ; *Veterans ; *Gram-Positive Bacterial Infections/drug therapy/microbiology ; Survival Analysis ; Anti-Bacterial Agents/therapeutic use ; *Communicable Diseases/drug therapy ; *Bacteremia/microbiology ; Referral and Consultation ; Treatment Outcome ; }, abstract = {OBJECTIVES: Infectious disease consultation (IDC) has been associated with improved outcomes in several infections, but the benefit of IDC among patients with enterococcal bacteraemia has not been fully evaluated.

METHODS: We performed a 1:1 propensity score-matched retrospective cohort study evaluating all patients with enterococcal bacteraemia at 121 Veterans Health Administration acute-care hospitals from 2011 to 2020. The primary outcome was 30-day mortality. We performed conditional logistic regression to calculate the OR to determine the independent association of IDC and 30-day mortality adjusted for vancomycin susceptibility and the primary source of bacteraemia.

RESULTS: A total of 12,666 patients with enterococcal bacteraemia were included; 8400 (63.3%) had IDC, and 4266 (36.7%) did not have IDC. Two thousand nine hundred seventy-two patients in each group were included after propensity score matching. Conditional logistic regression revealed that IDC was associated with a significantly lower 30-day mortality rate compared with patients without IDC (OR = 0.56; 95% CI, 0.50-0.64). The association of IDC was observed irrespective of vancomycin susceptibility, and when the primary source of bacteraemia was a urinary tract infection, or from an unknown primary source. IDC was also associated with higher appropriate antibiotic use, blood culture clearance documentation, and the use of echocardiography.

DISCUSSION: Our study suggests that IDC was associated with improved care processes and 30-day mortality rates among patients with enterococcal bacteraemia. IDC should be considered for patients with enterococcal bacteraemia.}, } @article {pmid36905704, year = {2023}, author = {Öztürk, Ç and Okcu, O and Öztürk, SD and Aşkan, G and Şen, B and Bedir, R}, title = {A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score.}, journal = {Annals of diagnostic pathology}, volume = {64}, number = {}, pages = {152128}, doi = {10.1016/j.anndiagpath.2023.152128}, pmid = {36905704}, issn = {1532-8198}, mesh = {Humans ; Female ; Prognosis ; *Tumor Microenvironment ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; }, abstract = {BACKGROUND AND OBJECTIVE: In recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated.

MATERIALS AND METHODS: In our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied.

RESULTS: The patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS 1 and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an independent risk factor for DFS (HR: 2.144 (95 % CI: 1.219-3.77) p: 0.008), but not an independent risk factor for OS.

CONCLUSION: CMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis.}, } @article {pmid36902676, year = {2023}, author = {Ruan, Z and Quan, Q and Wang, Q and Jiang, J and Peng, R}, title = {New Staging System and Prognostic Model for Malignant Phyllodes Tumor Patients without Distant Metastasis: A Development and Validation Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902676}, issn = {2077-0383}, support = {2022A1515012387//Basic and Applied Basic Research Fund of Guangdong Province/ ; }, abstract = {PURPOSE: To build a new staging system and new prognostic models for MPTB.

METHODS: We performed a comprehensive analysis of the data from the SEER database.

RESULTS: We discussed the characteristics of MPTB by comparing 1085 MPTB cases with 382,718 invasive ductal carcinoma cases. We established a new stage- and age-stratification system for MPTB patients. Furthermore, we built two prognostic models for MPTB patients. The validity of these models was confirmed through multifaceted and multidata verification.

CONCLUSIONS: Our study provided a staging system and prognostic models for MPTB patients, which can not only help to predict patient outcomes, but also enhance the understanding of the prognostic factors associated with MPTB.}, } @article {pmid36901095, year = {2023}, author = {Shenkman, G}, title = {The Mediating Role of Insecure Attachment in the Gap in Parenthood Desire between Lesbian and Gay Individuals and Their Heterosexual Counterparts.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901095}, issn = {1660-4601}, mesh = {Humans ; Male ; Female ; Heterosexuality ; Homosexuality, Male ; *Homosexuality, Female ; *Sexual and Gender Minorities ; Parenting ; }, abstract = {Previous studies have shown that lesbian and gay (LG) individuals, in comparison to their heterosexual counterparts, tend to report lower levels of parenthood desire. While numerous variables have been suggested to explain this gap in parenthood aspirations, no study has investigated the mediating role of avoidant attachment in the association between sexual orientation and parenthood desire. For that purpose, a sample of 790 cisgender Israelis aged 18-49 years (M = 28.27, SD = 4.76) was recruited using convenience sampling. Among the participants, 345 self-reported as predominantly or exclusively lesbian or gay and 445 self-reported as exclusively heterosexual. Participants completed online questionnaires assessing their sociodemographic characteristics, parenthood desire, and avoidant and anxious attachment styles. Mediation analyses were performed using the PROCESS macro, and the results revealed that LG individuals reported lower parenthood desire, higher avoidant attachment, and higher anxious attachment compared to heterosexual individuals. Moreover, avoidant attachment had a significant mediation effect in the association between sexual orientation and parenthood desire. The findings suggest that LG individuals are more likely to report higher avoidant attachment due to possible rejection and discrimination from family members and peers, and this may be associated with lower parenthood desire. The results contribute to the growing body of research on family formation and parenthood aspirations among LG individuals, and specifically studies aimed at delineating the factors that contribute to the gap in parenthood aspirations between sexual minority individuals and their heterosexual counterparts.}, } @article {pmid36900347, year = {2023}, author = {Lee, JH and Ryu, JM and Lee, SK and Chae, BJ and Lee, JE and Kim, SW and Nam, SJ and Yu, J}, title = {Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900347}, issn = {2072-6694}, abstract = {BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified.

METHODS: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis.

RESULTS: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM.

CONCLUSION: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.}, } @article {pmid36900164, year = {2023}, author = {Osiecki, R and Kozikowski, M and Sarecka-Hujar, B and Pyzlak, M and Dobruch, J}, title = {Prostate Cancer Morphologies: Cribriform Pattern and Intraductal Carcinoma Relations to Adverse Pathological and Clinical Outcomes-Systematic Review and Meta-Analysis.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900164}, issn = {2072-6694}, abstract = {The present study aimed to assess the association between the cribriform pattern (CP)/intraductal carcinoma (IDC) and the adverse pathological and clinical outcomes in the radical prostatectomy (RP) cohort. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA). The protocol from this review was registered on the PROSPERO platform. We searched PubMed[®], the Cochrane Library and EM-BASE[®] up to the 30th of April 2022. The outcomes of interest were the extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LNS met), risk of biochemical recurrence (BCR), distant metastasis (MET) and disease-specific death (DSD). As a result, we identified 16 studies with 164 296 patients. A total of 13 studies containing 3254 RP patients were eligible for the meta-analysis. The CP/IDC was associated with adverse outcomes, including EPE (pooled OR = 2.55, 95%CI 1.23-5.26), SVI (pooled OR = 4.27, 95%CI 1.90-9.64), LNs met (pooled OR = 6.47, 95%CI 3.76-11.14), BCR (pooled OR = 5.09, 95%CI 2.23-11.62) and MET/DSD (pooled OR = 9.84, 95%CI 2.75-35.20, p < 0.001). In conclusion, the CP/IDC belong to highly malignant prostate cancer patterns which have a negative impact on both the pathological and clinical outcomes. The presence of the CP/IDC should be included in the surgical planning and postoperative treatment guidance.}, } @article {pmid36897545, year = {2023}, author = {Kikuchi, M and Gomi, N and Ueki, A and Osako, T and Terauchi, T}, title = {Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {577-583}, pmid = {36897545}, issn = {1880-4233}, mesh = {Humans ; Female ; *BRCA1 Protein/genetics ; *Breast Neoplasms/diagnostic imaging/genetics ; BRCA2 Protein/genetics ; Retrospective Studies ; Genetic Predisposition to Disease ; Magnetic Resonance Imaging ; Germ-Line Mutation ; }, abstract = {BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.

METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen.

RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer.

CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.}, } @article {pmid36896205, year = {2023}, author = {Terasaki, A and Bando, H and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Kondo, Y and Hara, H}, title = {Local recurrence of breast cancer histologically resembling Paget disease presumably due to needle tract seeding: a case report.}, journal = {International cancer conference journal}, volume = {12}, number = {2}, pages = {143-148}, pmid = {36896205}, issn = {2192-3183}, abstract = {Seeding of cancer cells along the needle tract during core needle biopsy is a well-known phenomenon, with a reported frequency of between 22 and 50% [Hoorntje et al. in Eur J Surg Oncol 30:520-525, 2004;Liebens et al. in Maturitas 62:113-123, 2009;Diaz et al. in AJR Am J Roentgenol 173:1303-1313, 1999;]. Local recurrence due to needle tract seeding is rare because the immune system eliminates the cancer cells in most cases. In addition, most local recurrences due to needle tract seeding occur as invasive carcinoma after diagnosis of invasive ductal carcinoma of the breast or mucinous carcinoma, and needle tract seeding due to noninvasive carcinoma is uncommon. We herein report a rare case of local breast cancer recurrence histologically resembling Paget disease, presumably due to needle tract seeding after core needle biopsy for diagnosis of ductal carcinoma in situ of the breast. After receiving a diagnosis of ductal carcinoma in situ, the patient underwent skin-sparing mastectomy and breast reconstruction with a latissimus dorsi musculocutaneous flap. The pathological study showed ER/PgR-negative ductal carcinoma in situ, and no postoperative radiation therapy or systemic therapy was administered. Six months after the surgery, the patient had a breast cancer recurrence histologically resembling Paget disease, presumably in the scar of her core needle biopsy. The pathological study showed Paget disease localized in the epidermis, no invasive carcinoma, and no lymph node metastasis. It was morphologically similar to the primary lesion and was diagnosed as a local recurrence due to needle tract seeding.}, } @article {pmid36893606, year = {2023}, author = {Göransson, S and Chen, S and Olofsson, H and Larsson, O and Strömblad, S}, title = {An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).}, journal = {Biochemical and biophysical research communications}, volume = {654}, number = {}, pages = {73-79}, doi = {10.1016/j.bbrc.2023.03.001}, pmid = {36893606}, issn = {1090-2104}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Transcriptome ; Extracellular Matrix/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; *Carcinoma in Situ ; }, abstract = {Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.}, } @article {pmid36891453, year = {2023}, author = {Wadhwa, S and Ashwini, RK and Khadri, SIS}, title = {A Diagnostic Revelation: Case of a Mucinous Carcinoma of the Breast.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {1}, pages = {144-149}, pmid = {36891453}, issn = {0975-7651}, abstract = {Mucinous or colloid cancers are a rare subtype of invasive ductal carcinoma, making up only 2-3% of infiltrating carcinomas. Prevalence of pure mucinous breast cancer(PMBC) among infiltrating duct carcinomas in less than 60 year olds is 2-7%, and in less than 35 year olds, it is 1%. Mucinous carcinoma of the breast is divided into 2 subtypes, the pure type and mixed type. PMBC is characterized by a lower incidence of nodal involvement, favourable histological grade, and higher ER/PR expression. Axillary metastases are rare, though found in 12-14%. It has a better prognosis than infiltrative ductal cancer with 10-year survival being more than 90%. Here is the case of a 70-year-old female who presented with lump in the left breast since 3 years. On examination, we detected a left breast lump occupying the whole breast except lower outer quadrant, measuring 10 × 8 cm with overlying skin stretched with puckering and engorged veins seen, nipple displaced laterally and higher by 1 cm, firm to hard in consistency, and mobile with breast tissue. Sonomammography, mammography, FNAC and biopsy were suggestive of benign phyllodes tumour. Patient was hence posted for simple mastectomy on the left side with removal of attached lymph nodes (near axillary tail). Histopathological examination revealed pure mucinous breast carcinoma with nine lymph nodes, free from tumour and showing reactive hyperplasia. Immunohistochemistry studies demonstrated ER + , PR + , HER-2-NEU-. The patient was started on hormonal therapy. Therefore, mucinous carcinoma of the breast is a rare entity with imaging features sometimes mimicking a benign tumour such as Phyllodes tumour, hence making it important to include it as a differential diagnosis in our daily practice. It is especially important in the subtyping of carcinoma of the breast since it carries a favourable risk profile with less chances of lymph node involvement, higher hormone receptor positivity and good response to endocrine treatment.}, } @article {pmid36891420, year = {2023}, author = {Rateria, N and Naidu, PG and Tewari, M}, title = {Invasive Cancer in Accessory Axillary Breast: a Rare Presentation.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {1}, pages = {40-41}, pmid = {36891420}, issn = {0975-7651}, abstract = {Accessory breast tissue has an incidence of 0.3-6% and primary cancer arising in it is even rarer 0.2-0.6%. It may have aggressive course with tendency for early metastasis. Due to its rarity, variety of differentials, and lack of clinical awareness, treatment is usually delayed. We present here an interesting case of a 65-year-old lady with a 8 × 7-cm hard lump in right axillary region for 3 years with fungation for 3 months and with no concomitant breast lesion or axillary lymphadenopathy. Biopsy revealed invasive ductal carcinoma with no systemic metastasis. Management of accessory breast cancer follows same guidelines with primary treatment being wide excision and lymphadenectomy. Adjuvant therapies include radiotherapy and hormonal therapy.}, } @article {pmid36890060, year = {2023}, author = {Verspyck, E and Attal, N}, title = {Diagnosing nociplastic pain in cancer survivors: a major step forward.}, journal = {British journal of anaesthesia}, volume = {130}, number = {5}, pages = {515-518}, doi = {10.1016/j.bja.2023.02.006}, pmid = {36890060}, issn = {1471-6771}, mesh = {Humans ; *Cancer Survivors ; Pain ; *Fibromyalgia/complications/diagnosis/therapy ; Headache ; Pain Management ; *Neoplasms/complications ; }, abstract = {Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients.}, } @article {pmid36884000, year = {2023}, author = {Thapa, P and Singh, V and Gupta, K and Shrivastava, A and Kumar, V and Kataria, K and Mishra, PR and Mehta, DS}, title = {Point-of-care devices based on fluorescence imaging and spectroscopy for tumor margin detection during breast cancer surgery: Towards breast conservation treatment.}, journal = {Lasers in surgery and medicine}, volume = {55}, number = {4}, pages = {423-436}, doi = {10.1002/lsm.23651}, pmid = {36884000}, issn = {1096-9101}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Point-of-Care Systems ; Spectrum Analysis ; Optical Imaging ; *Carcinoma, Ductal ; }, abstract = {OBJECTIVE: Fluorescence-based methods are highly specific and sensitive and have potential in breast cancer detection. Simultaneous fluorescence imaging and spectroscopy during intraoperative procedures of breast cancer have great advantages in detection of tumor margin as well as in classification of tumor to healthy tissues. Intra-operative real-time confirmation of breast cancer tumor margin is the aim of surgeons, and therefore, there is an urgent need for such techniques and devices which fulfill the surgeon's priorities.

METHODS: In this article, we propose the development of fluorescence-based smartphone imaging and spectroscopic point-of-care multi-modal devices for detection of invasive ductal carcinoma in tumor margin during removal of tumor. These multimodal devices are portable, cost-effective, noninvasive, and user-friendly. Molecular level sensitivity of fluorescence process shows different behavior in normal, cancerous and marginal tissues. We observed significant spectral changes, such as, red-shift, full-width half maximum (FWHM), and increased intensity as we go towards tumor center from normal tissue. High contrast in fluorescence images and spectra are also recorded for cancer tissues compared to healthy tissues. Preliminary results for the initial trial of the devices are reported in this article.

RESULTS: A total 44 spectra from 11 patients of invasive ductal carcinoma (11 spectra for invasive ductal carcinoma and rest are normal and negative margins) are used. Principle component analysis is used for the classification of invasive ductal carcinoma with an accuracy of 93%, specificity of 75% and sensitivity of 92.8%. We obtained an average 6.17 ± 1.66 nm red shift for IDC with respect to normal tissue. The red shift and maximum fluorescence intensity indicates p < 0.01. These results described here are supported by histopathological examination of the same sample.

CONCLUSION: In the present manuscript, simultaneous fluorescence-based imaging and spectroscopy is accomplished for the classification of IDC tissues and breast cancer margin detection.}, } @article {pmid36883497, year = {2023}, author = {}, title = {Yassir Alaa Muhammed Hassan Shubbar CORRELATION BETWEEN DIFFERENT CLINICOPATHOLOGICAL PARAMETERS AND MOLECULAR SUBTYPES OF FEMALE BREAST CARCINOMA IN SOUTH REGION OF IRAQ.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {76}, number = {1}, pages = {97-107}, doi = {10.36740/WLek202301114}, pmid = {36883497}, issn = {0043-5147}, mesh = {Female ; Humans ; *Breast Neoplasms/chemistry/metabolism/pathology ; Iraq ; Ki-67 Antigen/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; *Carcinoma, Ductal, Breast/chemistry/metabolism/pathology ; Receptor, ErbB-2/analysis/metabolism ; Immunohistochemistry ; }, abstract = {OBJECTIVE: The aim: To correlate variable clincopathological parameters with molecular subtypes of the breast carcinoma, which affect the prognosis and management of breast malignancy.

PATIENTS AND METHODS: Materials and methods: In this study a total of 511 female patients with breast carcinoma were included, ranging from 32 to 85 years of age, with 35.8% premenopausal and 64.1% being post-menopausal. The sample slides were stained immunohistochemically for estrogen receptors (ER), progesterone receptors (PR), ki67 and HER2, the tumors were graded histologically using the Nottingham criteria system.

RESULTS: Results: Most tumors (72.8%) ranged between 2 and 5 cm in size; the most common histological type of breast carcinoma (49.7%) was invasive ductal carcinoma of no special type, with grade 2 presented in 51.8% cases; most frequent stage at time of presentation was stage 3A, found in 39.9%; the most frequent molecular subtype was ER and/or PR+, Her2- with low proliferation rate ki67<14% subtype in 48.5%, and those group were more likely (statistically significant) to be older, have stage 3 breast cancer, present with tumor size between 2 and 5 cm and tend to be well differentiated histological grade (grade1), mostly with lymph node positive, and most likely have tumor type of invasive ductal carcinoma of no special type.

CONCLUSION: Conclusions: the most common histological type of breast carcinoma in Iraq south was invasive ductal carcinoma of no special type and most cases showed (ER and/or PR+, HER 2-, low ki67) as the most common molecular subtype.}, } @article {pmid36883168, year = {2023}, author = {Heller, B and Amir, A and Waxman, R and Maaravi, Y}, title = {Hack your organizational innovation: literature review and integrative model for running hackathons.}, journal = {Journal of innovation and entrepreneurship}, volume = {12}, number = {1}, pages = {6}, pmid = {36883168}, issn = {2192-5372}, abstract = {This article aims to offer a comprehensive overview of the existing literature on the hackathon phenomenon to offer scholars a common ground for future research and managers and practitioners research-based guidelines on best planning and running a hackathon. A review of the most relevant literature on hackathons was conducted to serve as the research basis for our integrative model and guidelines. This article synthesizes the research on hackathons to offer comprehensible guidelines for practitioners while also providing questions for future hackathon researchers. We differentiate between the different design characteristics of hackathons while noting their advantages and disadvantages, discuss tools and methodologies for successful hackathon setup and execution step-by-step, and provide recommendations to encourage project continuity.}, } @article {pmid36883155, year = {2022}, author = {Ali Khadem, Z and Abdul Wadood Al-Shammaree, S}, title = {Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.}, journal = {Archives of Razi Institute}, volume = {77}, number = {4}, pages = {1341-1348}, pmid = {36883155}, issn = {2008-9872}, mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Breast Neoplasms/chemistry/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/chemistry/genetics/metabolism/pathology ; *Estradiol/analysis/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/analysis/genetics/metabolism ; Iraq/epidemiology ; Prognosis ; *Tumor Suppressor Protein p53/analysis/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.}, } @article {pmid36880192, year = {2023}, author = {Zhao, Y and Chai, N and Li, S and Yan, L and Zhou, C and He, J and Zhang, H}, title = {Evaluation of the efficacy of chemotherapy for tubular carcinoma of the breast: A Surveillance, Epidemiology, and End Results cohort study.}, journal = {Cancer medicine}, volume = {12}, number = {9}, pages = {10326-10339}, pmid = {36880192}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/pathology ; Cohort Studies ; *Breast Neoplasms/drug therapy/epidemiology ; *Adenocarcinoma ; Propensity Score ; }, abstract = {BACKGROUND: The use of systematic treatment for tubular carcinoma (TC) of the breast remained controversial. This study aimed to explore the efficacy of chemotherapy on TC to develop individualized treatment strategies.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 6486 eligible cases with TC and 309,304 with invasive ductal carcinoma (IDC) were collected. Breast cancer-specific survival (BCSS) was assessed through multivariable Cox analyses and Kaplan-Meier analyses. Differences between groups were balanced using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).

RESULTS: Compared with IDC patients, TC patients had a more favorable long-term BCSS after PSM (hazard ratio = 0.62, p = 0.004) and IPTW (hazard ratio = 0.61, p < 0.001). Chemotherapy was an unfavorable predictor of BCSS for TC (hazard ratio = 3.20, p < 0.001). After stratifying by hormone receptor (HR) and lymph node (LN) status, chemotherapy was correlated with worse BCSS in the HR+/LN- subgroup (hazard ratio = 6.95, p = 0.001) but showed no impact on BCSS in the HR+/LN+ (hazard ratio = 0.75, p = 0.780) and HR-/LN- (hazard ratio = 7.87, p = 0.150) subgroups.

CONCLUSIONS: Tubular carcinoma is a low-grade malignant tumor with favorable clinicopathological features and excellent long-term survival. Adjuvant chemotherapy was not recommended for TC regardless of HR and LN status, while the therapy regimens should be carefully individualized.}, } @article {pmid36876593, year = {2023}, author = {Wang, L and Luo, R and Chen, Y and Liu, H and Guan, W and Li, R and Zhang, Z and Duan, S and Wang, D}, title = {Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {4}, pages = {1303-1313}, doi = {10.1002/jmri.28670}, pmid = {36876593}, issn = {1522-2586}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; Tumor Burden ; Retrospective Studies ; Magnetic Resonance Imaging ; Breast/diagnostic imaging/pathology ; Diffusion Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI).

PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs.

STUDY TYPE: Retrospective.

SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days).

FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging.

ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation.

STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R[2] and root mean square error (RMSE).

RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R[2] and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days).

DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36876173, year = {2023}, author = {Akbari, ME and Akbari, A and Khayamzadeh, M and Salmanian, R and Akbari, M}, title = {Ten-Year Survival of Breast Cancer in Iran: A National Study (Retrospective Cohort Study).}, journal = {Breast care (Basel, Switzerland)}, volume = {18}, number = {1}, pages = {12-21}, pmid = {36876173}, issn = {1661-3791}, abstract = {PURPOSE: This study aimed to estimate the 5- and 10-year survival rates of breast cancer in Iran.

METHODS: This retrospective cohort study was performed in 2019 on breast cancer patients registered in the national cancer registry system of Iran during 2007-2014. The patients were contacted to collect their information and status (alive or dead). Age and pathological type of tumor were categorized into five groups, and the place of residence was divided into 13 regions. The Kaplan-Meier method and the Cox proportional hazards model were used for data analysis.

RESULTS: A total of 87,902 patients were diagnosed with breast cancer during the study, 22,307 of whom were followed-up. The 5- and 10-year survival rates of the patients were 80% and 69%, respectively. The mean age of the patients was 50.68 ± 12.76 years (median age, 49 years). About 2.3% of the patients were male. The 5- and 10-year survival rates were 69% and 50% in men, respectively. The highest survival rate was reported in the age group of 40-49 years, and the lowest rate was found in the age group of ≥70 years. Of all pathological types, 88% were found in the invasive ductal carcinoma group; the highest survival rate was reported in the noninvasive carcinoma group. The highest survival rate was reported in the Tehran region and the lowest in the Hamedan region. Based on the results, the Cox proportional hazards model, sex, age group, and pathological type were statistically significant differences.

CONCLUSION: This nationwide study performed on breast cancer patients indicated an improvement in the overall survival rate of these patients over the past years (the 5-year survival rate increased from 71% in 2011 to 80% in the present study), which might be attributed to advances in cancer management.}, } @article {pmid36868097, year = {2023}, author = {Aktan, Ç and Küçükaslan, AŞ and Türk, BA and Yildirim, I}, title = {Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.}, journal = {Pathology, research and practice}, volume = {244}, number = {}, pages = {154391}, doi = {10.1016/j.prp.2023.154391}, pmid = {36868097}, issn = {1618-0631}, mesh = {Female ; Humans ; *RNA, Long Noncoding/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Treatment Outcome ; *Breast Neoplasms/pathology ; }, abstract = {AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast.

MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version.

RESULTS: The mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings.

CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.}, } @article {pmid36868037, year = {2023}, author = {Abate, F and Russo, M and Ricciardi, C and Tepedino, MF and Romano, M and Erro, R and Pellecchia, MT and Amboni, M and Barone, P and Picillo, M}, title = {Wearable sensors for assessing disease severity and progression in Progressive Supranuclear Palsy.}, journal = {Parkinsonism & related disorders}, volume = {109}, number = {}, pages = {105345}, doi = {10.1016/j.parkreldis.2023.105345}, pmid = {36868037}, issn = {1873-5126}, mesh = {Humans ; *Supranuclear Palsy, Progressive/diagnosis ; Patient Acuity ; Severity of Illness Index ; Gait ; *Wearable Electronic Devices ; Disease Progression ; }, abstract = {INTRODUCTION: Progressive supranuclear palsy (PSP) is an atypical parkinsonism characterized by prominent gait and postural impairment. The PSP rating scale (PSPrs) is a clinician-administered tool to evaluate disease severity and progression. More recently, digital technologies have been used to investigate gait parameters. Therefore, object of this study was to implement a protocol using wearable sensors evaluating disease severity and progression in PSP.

METHODS: Patients were evaluated with the PSPrs as well as with three wearable sensors located on the feet and lumbar area. Spearman coefficient was used to assess the relationship between PSPrs and quantitative measurements. Furthermore, sensor parameters were included in a multiple linear regression model to assess their ability in predicting the PSPrs total score and sub-scores. Finally, differences between baseline and three-month follow-up were calculated for PSPrs and each quantitative variable. The significance level in all analyses was set at ≤ 0.05.

RESULTS: Fifty-eight evaluations from thirty-five patients were analyzed. Quantitative measurements showed multiple significant correlations with the PSPrs scores (r between 0.3 and 0.7; p < 0.05). Linear regression models confirmed the relationships. After three months visit, significant worsening from baseline was observed for cadence, cycle duration and PSPrs item 25, while PSPrs item 10 showed a significant improvement.

CONCLUSION: We propose wearable sensors can provide an objective, sensitive quantitative evaluation and immediate notification of gait changes in PSP. Our protocol can be easily introduced in outpatient and research settings as a complementary tool to clinical measures as well as an informative tool on disease severity and progression in PSP.}, } @article {pmid36866842, year = {2023}, author = {Abdollahpour, N and Helali, F and Rasoulzadeh, Y and Hassankhani, H}, title = {Barriers and Challenges to Human Factors/Ergonomics Knowledge Transfer to Small Business Enterprises in an Industrially Developing Country.}, journal = {IISE transactions on occupational ergonomics and human factors}, volume = {11}, number = {1-2}, pages = {14-31}, doi = {10.1080/24725838.2023.2179687}, pmid = {36866842}, issn = {2472-5846}, abstract = {OCCUPATIONAL APPLICATIONWe found that small business enterprises (SBEs) face intra- and extra-organizational barriers in different dimensions related to their work system to practically implement human factors/ergonomics (HFE) knowledge transfer and to achieve its benefits in an industrially developing country. Utilizing a three-zone lens, we evaluated the feasibility of overcoming the barriers identified by stakeholders, especially ergonomists. To overcome the identified barriers in practice, three types of macroergonomics interventions (top-down, middle-out, and bottom-up) were distinguished through macroergonomics theory. The bottom-up approach of macroergonomics, as a participatory HFE intervention, was considered as the entry point to overcome the perceived barriers in the first zone of the lens, which included such themes as lack of competence, lack of involvement and interaction, and inefficient training and learning approaches. This approach focused on improving emotional literacy as a care zone among the small business enterprise personnel.}, } @article {pmid36863342, year = {2023}, author = {Aggius-Vella, E and Chebat, DR and Maidenbaum, S and Amedi, A}, title = {Activation of human visual area V6 during egocentric navigation with and without visual experience.}, journal = {Current biology : CB}, volume = {33}, number = {7}, pages = {1211-1219.e5}, doi = {10.1016/j.cub.2023.02.025}, pmid = {36863342}, issn = {1879-0445}, mesh = {Humans ; *Auditory Perception ; *Movement/physiology ; Motion ; Hearing ; Eye Movements ; }, abstract = {V6 is a retinotopic area located in the dorsal visual stream that integrates eye movements with retinal and visuo-motor signals. Despite the known role of V6 in visual motion, it is unknown whether it is involved in navigation and how sensory experiences shape its functional properties. We explored the involvement of V6 in egocentric navigation in sighted and in congenitally blind (CB) participants navigating via an in-house distance-to-sound sensory substitution device (SSD), the EyeCane. We performed two fMRI experiments on two independent datasets. In the first experiment, CB and sighted participants navigated the same mazes. The sighted performed the mazes via vision, while the CB performed them via audition. The CB performed the mazes before and after a training session, using the EyeCane SSD. In the second experiment, a group of sighted participants performed a motor topography task. Our results show that right V6 (rhV6) is selectively involved in egocentric navigation independently of the sensory modality used. Indeed, after training, rhV6 of CB is selectively recruited for auditory navigation, similarly to rhV6 in the sighted. Moreover, we found activation for body movement in area V6, which can putatively contribute to its involvement in egocentric navigation. Taken together, our findings suggest that area rhV6 is a unique hub that transforms spatially relevant sensory information into an egocentric representation for navigation. While vision is clearly the dominant modality, rhV6 is in fact a supramodal area that can develop its selectivity for navigation in the absence of visual experience.}, } @article {pmid36856731, year = {2023}, author = {Cao, S and Kalin, ML and Huang, X}, title = {EPISOL: A software package with expanded functions to perform 3D-RISM calculations for the solvation of chemical and biological molecules.}, journal = {Journal of computational chemistry}, volume = {44}, number = {17}, pages = {1536-1549}, doi = {10.1002/jcc.27088}, pmid = {36856731}, issn = {1096-987X}, mesh = {Thermodynamics ; Solvents/chemistry ; Solutions ; Computer Simulation ; *Software ; }, abstract = {Integral equation theory (IET) provides an effective solvation model for chemical and biological systems that balances computational efficiency and accuracy. We present a new software package, the expanded package for IET-based solvation (EPISOL), that performs 3D-reference interaction site model (3D-RISM) calculations to obtain the solvation structure and free energies of solute molecules in different solvents. In EPISOL, we have implemented 22 different closures, multiple free energy functionals, and new variations of 3D-RISM theory, including the recent hydrophobicity-induced density inhomogeneity (HI) theory for hydrophobic solutes and ion-dipole correction (IDC) theory for negatively charged solutes. To speed up the convergence and enhance the stability of the self-consistent iterations, we have introduced several numerical schemes in EPISOL, including a newly developed dynamic mixing approach. We show that these schemes have significantly reduced the failure rate of 3D-RISM calculations compared to AMBER-RISM software. EPISOL consists of both a user-friendly graphic interface and a kernel library that allows users to call its routines and adapt them to other programs. EPISOL is compatible with the force-field and coordinate files from both AMBER and GROMACS simulation packages. Moreover, EPISOL is equipped with an internal memory control to efficiently manage the use of physical memory, making it suitable for performing calculations on large biomolecules. We demonstrate that EPISOL can efficiently and accurately calculate solvation density distributions around various solute molecules (including a protein chaperone consisting of 120,715 atoms) and obtain solvent free energy for a wide range of organic compounds. We expect that EPISOL can be widely applied as a solvation model for chemical and biological systems. EPISOL is available at https://github.com/EPISOLrelease/EPISOL.}, } @article {pmid36856291, year = {2023}, author = {Johnson, HM and Valero, V and Yang, WT and Smith, BD and Krishnamurthy, S and Shen, Y and Lin, H and Lucci, A and Rauch, GM and Kuerer, HM}, title = {Eliminating Breast Surgery for Invasive Cancer with Exceptional Response to Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint.}, journal = {Journal of the American College of Surgeons}, volume = {237}, number = {1}, pages = {101-108}, doi = {10.1097/XCS.0000000000000670}, pmid = {36856291}, issn = {1879-1190}, mesh = {Female ; Humans ; Middle Aged ; Aged ; Neoadjuvant Therapy/methods ; *Triple Negative Breast Neoplasms/drug therapy ; Prospective Studies ; Feasibility Studies ; Neoplasm Recurrence, Local/prevention & control ; *Breast Neoplasms/surgery/drug therapy ; Receptor, ErbB-2/metabolism/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

STUDY DESIGN: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with <2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

RESULTS: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were White (69.2%) and non-Hispanic/Latino (84.6%). All patients had invasive ductal carcinoma (6 TNBC, 7 HER2+BC). Mean tumor size was 2.4 cm (range 0.9 to 5.0) before NST and 0.7 cm (range 0 to 1.8) after NST. Seven patients (53.8%) had residual disease identified on VACB; the remaining 6 (46.2%) comprised the feasibility cohort. At a median follow-up of 44.3 months (range 41.3 to 51.3) there was no ipsilateral breast tumor recurrence in this cohort.

CONCLUSIONS: These early data suggest that omission of breast surgery in patients with invasive TNBC and HER2+BC with no evidence of residual disease on standardized VACB after NST is potentially feasible. Results from the expansion phase of this clinical trial will be reported per protocol prespecified analyses.}, } @article {pmid36853294, year = {2023}, author = {Montazer, F and Boozari, B and Alizadeh-Navaei, R}, title = {Evaluation of LGR5 Cancer Stem Cell Marker Expression in Breast Cancer and Its Relationship with Hormonal Profile and Clinical Pathological Features.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {24}, number = {2}, pages = {467-470}, pmid = {36853294}, issn = {2476-762X}, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Breast Neoplasms ; Cross-Sectional Studies ; Cytoplasm ; Iran/epidemiology ; Neoplastic Stem Cells ; Receptors, G-Protein-Coupled ; Adult ; }, abstract = {BACKGROUND: Due to the high prevalence of breast cancer and the importance of evaluating new prognostic criteria for effective treatment of these patients, this study was performed to investigate the role of LGR5 in breast cancer and its relationship with hormonal and clinicalopathological features of the disease.

METHODS: This cross-sectional study was performed on breast cancer tissue samples in the archives of the pathology department of Firoozabadi Hospital in Tehran between 2019 and 2021. Inclusion criteria included invasive ductal carcinoma and exclusion criteria were preoperative chemotherapy. Blocks were examined for LGR5 marker expression by IHC method using LGR5 monoclonal antibody kits (Abcam). The expression pattern of LGR5 marker was cytoplasmic and cells presenting brown staining in the cytoplasm were considered positive for this marker and in terms of distribution and severity of staining were divided into three groups: mild, moderate and severe.

RESULTS: This study was performed on 60 patients with breast cancer with a mean age of 55.5±9.7. Most of the patients (55%) were in grade II. The KI67 marker was positive in 45 cases (75%) and the HER2 marker in 14 cases (23.3%) and 8 cases (13.3%) were triple-negative. The expression severity of staining of LGR5 marker in 41 cases (68.3%) was moderate and the distribution of marker expression in 31 cases (51.7%) was moderate. No significant relationship was observed between LGR5 expression severity and tumor characteristics.

CONCLUSION: LGR5 marker is expressed in a remarkable percentage of breast cancer patients and has no significant relationship with tumor characteristics.}, } @article {pmid36850582, year = {2023}, author = {Russo, M and Amboni, M and Barone, P and Pellecchia, MT and Romano, M and Ricciardi, C and Amato, F}, title = {Identification of a Gait Pattern for Detecting Mild Cognitive Impairment in Parkinson's Disease.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {4}, pages = {}, pmid = {36850582}, issn = {1424-8220}, support = {FARB2019//University of Salerno/ ; }, mesh = {Humans ; Bayes Theorem ; *Parkinson Disease/diagnosis ; Gait ; Gait Analysis ; *Cognitive Dysfunction/diagnosis ; }, abstract = {The aim of this study was to determine a gait pattern, i.e., a subset of spatial and temporal parameters, through a supervised machine learning (ML) approach, which could be used to reliably distinguish Parkinson's Disease (PD) patients with and without mild cognitive impairment (MCI). Thus, 80 PD patients underwent gait analysis and spatial-temporal parameters were acquired in three different conditions (normal gait, motor dual task and cognitive dual task). Statistical analysis was performed to investigate the data and, then, five ML algorithms and the wrapper method were implemented: Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB), Support Vector Machine (SVM) and K-Nearest Neighbour (KNN). First, the algorithms for classifying PD patients with MCI were trained and validated on an internal dataset (sixty patients) and, then, the performance was tested by using an external dataset (twenty patients). Specificity, sensitivity, precision, accuracy and area under the receiver operating characteristic curve were calculated. SVM and RF showed the best performance and detected MCI with an accuracy of over 80.0%. The key features emerging from this study are stance phase, mean velocity, step length and cycle length; moreover, the major number of features selected by the wrapper belonged to the cognitive dual task, thus, supporting the close relationship between gait dysfunction and MCI in PD.}, } @article {pmid36848617, year = {2023}, author = {Esserman, LJ and Ali, H and McKenzie, T}, title = {When Less Can Be More: How the 10-Year Updated Results From the Randomized Controlled AMAROS Trial Should Affect Axillary Management in the Setting of a Positive Node.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {41}, number = {12}, pages = {2144-2150}, doi = {10.1200/JCO.22.02070}, pmid = {36848617}, issn = {1527-7755}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/drug therapy ; Axilla/pathology ; Mastectomy ; *Lymphedema ; Mastectomy, Segmental ; Randomized Controlled Trials as Topic ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.It is important to reflect on how far we as a medical community have come when treating breast cancer. Ongoing research, clinical trials, and better understanding of biology have transformed our understanding and treatment of breast cancer. There is still much to learn. Although progress was slow for decades, treatments have evolved more quickly in the recent past. The Halsted radical mastectomy, first popularized in 1894, was performed for almost a century, and although it decreased local recurrence, it did not improve survival. This well-intentioned surgery disfigured women and was abandoned as better systemic therapies were introduced and less aggressive surgical procedures were found to be equivalent in clinical trials. The evolution of trials in the modern era has taught us an important lesson. De-escalation of surgical interventions in the setting of improved systemic therapy can lead to better patient outcomes. We present a case of a clinician with an early-stage invasive ductal carcinoma responsive to neoadjuvant endocrine therapy and who subsequently underwent a partial mastectomy with axillary sentinal lymph node biopsy. Although clinically node-negative, she was pathologically node-positive, and concerned about both optimizing her outcomes and minimizing the risk of lymphedema. The release of 10-year follow-up data from the AMAROS trial furthers our knowledge and understanding of the impact of local control measures of the axilla. The concepts illustrated by the findings of AMAROS may be applied in clinical practice and ultimately help us make rational treatment choices and support shared decision making for patients like ours.}, } @article {pmid36843866, year = {2023}, author = {Mansoor, NS and Arifin, F and Kornain, NKM and Razalli, MM}, title = {A rare invasive male breast cancer of nonspecific type presenting at a primary care clinic: Importance of early diagnosis and management.}, journal = {Journal of family & community medicine}, volume = {30}, number = {1}, pages = {65-67}, pmid = {36843866}, issn = {1319-1683}, abstract = {Male breast cancer is a rare disease with an incidence rate of <1% of all breast cancer cases, and only 1% of all male malignancies. Men tend to present at an older age and with more advanced stages compared to women. We report a case of a 74-year-old man who presented at a primary care clinic with a right subareolar painless breast mass. A mammogram and core biopsy were performed. A diagnosis of right invasive breast carcinoma was rendered. The patient underwent a right total mastectomy with ipsilateral axillary lymph node dissection, which revealed an invasive ductal carcinoma of no special type (NST). Chemotherapy, radiotherapy, and hormonal therapy were included in the adjuvant treatment plan. In this report, we discuss the important role of the primary care physician (PCP) in early diagnosis and referral for definitive management. The PCP also plays an essential role in the holistic care of male breast cancer patients, including the management of physical, psychological, social, and underlying chronic diseases.}, } @article {pmid36827339, year = {2023}, author = {Kelly, HK and Geller, S and Swami, V and Shenkman, G and Levy, S and Ridge, D}, title = {A relational investigation of Israeli gay fathers' experiences of surrogacy, early parenthood, and mental health in the context of the COVID-19 pandemic.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0282330}, pmid = {36827339}, issn = {1932-6203}, mesh = {Male ; Pregnancy ; Infant ; Child ; Female ; Humans ; Fathers/psychology ; Mental Health ; Israel ; Pandemics ; Surrogate Mothers/psychology ; *COVID-19 ; Parenting/psychology ; *Sexual and Gender Minorities ; }, abstract = {Perinatal distress affects approximately 10% of fathers, but little is known about how gay fathers experience the challenges surrounding childbirth and early parenting of a child. This study explored gay fathers' experiences of having a baby via transnational surrogacy, raising that baby as a gay parent, and the context of the COVID-19 pandemic. In-depth qualitative interviews were conducted with 15 Israeli men to understand their experiences of surrogacy and early parenthood, focusing on the impact on their mental health and the relational factors involved. Secondary narrative analysis revealed that fathers constructed surrogacy as a perilous quest that required strong intentionality to undertake. The first year of parenthood was conceptualised alternately as a joyful experience and/or one that challenged fathers' identities and mental health. A relational framework was applied to better conceptualise the fathers' narratives, revealing that actual connections-and the potentials for links-considerably shaped experiences of surrogacy, perinatal distress and recovery. Implications for research and policy are discussed.}, } @article {pmid36819928, year = {2023}, author = {Rounds, AK and Tractenberg, RE and Groah, SL and Frost, JK and Ljungberg, IH and Navia, H and Pham, CT}, title = {Urinary Symptoms Are Unrelated to Leukocyte Esterase and Nitrite Among Indwelling Catheter Users.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {1}, pages = {82-93}, pmid = {36819928}, issn = {1945-5763}, mesh = {Humans ; *Urinary Tract Infections/diagnosis ; Nitrites ; Urinary Bladder ; Prospective Studies ; Predictive Value of Tests ; Catheters, Indwelling ; *Spinal Cord Injuries ; *Spinal Cord Diseases ; }, abstract = {OBJECTIVES: To explore the association between dipstick results and urinary symptoms.

METHOD: This was a prospective 12-month observational study of real-time self-administered urine dipstick results and symptoms in a community setting that included 52 spinal cord injury/disease (SCI/D) participants with neurogenic lower urinary tract dysfunction (NLUTD) who use an indwelling catheter. Symptoms were collected using the Urinary Symptom Questionnaire for Neurogenic Bladder-Indwelling Catheter (USQNB-IDC). The USQNB-IDC includes actionable (A), bladder (B1), urine quality (B2), and other (C) symptoms; analyses focused on A, B1, and B2 symptoms. Dipstick results include nitrite (NIT +/-), and leukocyte esterase (LE; negative, trace, small, moderate, or large). Dipstick outcomes were defined as strong positive (LE = moderate/large and NIT+), inflammation positive (LE = moderate/large and NIT-), negative (LE = negative/trace and NIT-), and indeterminate (all others).

RESULTS: Nitrite positive dipsticks and moderate or large LE positive dipsticks were each observed in over 50% of the sample in every week. Strong positive dipstick results were observed in 35% to 60% of participants in every week. A, B1, or B2 symptoms co-occurred less than 50% of the time with strong positive dipsticks, but they also co-occurred with negative dipsticks. Participants were asymptomatic with a strong positive dipstick an average of 30.2% of the weeks. On average, 73% of the time a person had a negative dipstick, they also had no key symptoms (95% CI, .597-.865).

CONCLUSION: No association was observed between A, B1, and B2 symptoms and positive dipstick. A negative dipstick with the absence of key symptoms may better support clinical decision-making.}, } @article {pmid36819793, year = {2022}, author = {Wuraola, FO and Olasehinde, O and Di Bernardo, M and Akinkuolie, AA and Adisa, AO and Aderounmu, AA and Mohammed, TO and Omoyiola, OZ and Kingham, TP and Alatise, OI}, title = {Breast cancer in elderly patients: a clinicopathological review of a Nigerian database.}, journal = {Ecancermedicalscience}, volume = {16}, number = {}, pages = {1484}, pmid = {36819793}, issn = {1754-6605}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Breast cancer in the elderly population has not been evaluated in the Nigerian context. With the rising incidence of breast cancer and the changing demographics, it is likely that an increasing number of elderly patients will be managed in the coming years in Nigeria. This review describes the clinicopathological profile of elderly patients with breast cancer in a Nigerian database.

METHOD: From a prospective institutional database, elderly patients (65 years and above) managed for breast cancer over a 9-year period were reviewed. Details of their socio-demographic characteristics, patterns of presentation, pathology, treatment and outcome were obtained and analysed.

RESULTS: Of the 607 patients managed during the study period, there were 87 older patients accounting for 14.3% of the total. There was a progressive rise in the number of patients with breast cancer towards the latter part of the study. Expectedly, they were all post-menopausal, with their ages ranging from 65 to 92 years, with a mean of 71 ± 6.58 years. Systemic hypertension was the commonest co-morbidity (29.8%). The mean tumour size at presentation was 10 cm, with the majority presenting with stage 3 disease. Invasive ductal carcinoma was the predominant histological type 83 (95.4%); 44.4% of those who had immunohistochemistry were oestrogen receptor-positive. Approximately half underwent mastectomy (52.8%), 63 (72.4%) had chemotherapy, 8 (44.4%) had hormonal therapy and only 6 (6.9%) had combined multimodal therapy in addition to surgery. Overall 5-year survival was 42.1%.

CONCLUSION: The pattern of presentation and outcomes of care in this elderly cohort is similar to the general population. Early presentation and use of multimodal treatment is still the mainstay of survival.}, } @article {pmid36816390, year = {2022}, author = {Balsak, S and Yozgat, CY and Yuzkan, S and Uyar, A}, title = {Comparison of ultrasonographic and mammographic features of extremely rare papillary carcinoma and invasive ductal carcinoma.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {26}, number = {4}, pages = {275-281}, pmid = {36816390}, issn = {1428-2526}, abstract = {INTRODUCTION: This study aimed to investigate and compare ultrasonographic and mammographic findings of papillary breast carcinoma and invasive ductal carcinoma in breast masses that were diagnosed as pathological.

MATERIAL AND METHODS: This retrospective study included 88 patients with breast lesions, who underwent ultrasonography, mediolateral oblique-craniocaudal, and tomosynthesis imaging in the Picture Archiving and Communication System between January 2010 and March 2019.

RESULTS: 44 histopathologically diagnosed papillary carcinoma patients and 44 invasive ductal carcinoma patients were divided into groups according to contour, shape, internal structure, calcific-cystic component, echogenicity, posterior acoustic change, skin orientation, and environmental echogenic halo. There was a statistically significant difference between the groups in mammography contour, U/S contour, U/S shape, U/S posterior acoustics, and U/S internal structure. Logistic regression analysis showed that the presence of homogenous appearance (p < 0.001) and absence of shading in the posterior acoustic U/S (p = 0.001) were the most pertinent findings for determining papillary carcinoma. In the U/S, the likelihood of a homogenous tumour being a papillary carcinoma was 16.869 times higher than that of invasive ductal carcinoma, whereas the same probability was 0.1101 times less for a tumour with posterior acoustic shadowing.

CONCLUSIONS: It is challenging to differentiate between invasive ductal carcinoma and papillary carcinoma of the breast without histopathological diagnosis both on ultrasound and mammography. The results of our study demonstrated that the ultrasonographic and mammographic findings of invasive ductal carcinoma and papillary carcinoma were like each other. Therefore, it is still not possible to distinguish between these 2 types of cancer only in accordance with these 2 criteria.}, } @article {pmid36809741, year = {2023}, author = {Kor, A and Shoshani, A}, title = {Moderating the impact of the COVID-19 pandemic on children's and adolescents' substance use, digital media use, and mental health: A randomized positive psychology addiction prevention program.}, journal = {Addictive behaviors}, volume = {141}, number = {}, pages = {107660}, pmid = {36809741}, issn = {1873-6327}, mesh = {Humans ; Child ; Adolescent ; Mental Health ; Pandemics ; *COVID-19 ; Internet ; Psychology, Positive ; *Substance-Related Disorders/prevention & control ; }, abstract = {OBJECTIVE: Previous research suggests that well-being interventions are effective in moderating substance and digital media use and improving mental health. This study evaluated the feasibility and preliminary efficacy of a school-based Positive Psychology Addiction Prevention (PPAP) intervention aimed at reducing substance and digital media use and increasing the mental health of school children during the COVID-19 pandemic.

METHODS: The sample was composed of 1,670 children and adolescents (Mean age = 12.96, SD = 2.01) from six elementary and secondary schools in Israel who were randomly assigned to the PPAP intervention (n = 833) or the waiting-list control conditions (n = 837). A three-year longitudinal repeated-measures randomized control design was used to examine modifications in substance use, digital media use, and psychological symptoms in the intervention and control groups assessed on the pre-test (before the outbreak of COVID-19, September 2019), the post-test (May 2021), and the 12-month follow-up (May 2022).

RESULTS: The 12-month prevalence of tobacco use, alcohol use, and cannabis use decreased significantly from the pre- to the follow-up period in the intervention group, and increased significantly in the control group. Daily digital media use increased during the pandemic period in both groups, with a significantly higher increase in the control group. The intervention group reported significantly lower psychological symptoms and negative emotions, and greater positive emotions and life satisfaction after the intervention and at follow-up compared to the control group.

CONCLUSIONS: The COVID-19 pandemic has profoundly disrupted the lives of children and adolescents. Well-being and addiction prevention interventions may be effective in improving the mental health of school children during pandemics and crisis periods.}, } @article {pmid36805386, year = {2023}, author = {Kwong, A and Co, M and Fukuma, E}, title = {Prospective Clinical Trial on Expanding Indications for Cryosurgery for Early Breast Cancers.}, journal = {Clinical breast cancer}, volume = {23}, number = {4}, pages = {363-368}, doi = {10.1016/j.clbc.2023.01.007}, pmid = {36805386}, issn = {1938-0666}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/surgery/pathology ; *Cryosurgery/adverse effects ; Neoplasm, Residual/surgery ; Prospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; }, abstract = {INTRODUCTION: This is a prospective single arm clinical trial on cryosurgery for early breast cancers, to evaluate the expanded criteria to tumors larger than 1.5 cm and non-luminal breast cancers.

METHODS: Inclusion criteria include Solitary T1 breast cancers of any immunohistotypes. Cryosurgery was performed using the IceCure ProSense Cryoablation System. Lumpectomy of the cryoablated tumor was then performed 8 weeks after cryosurgery.

RESULTS: Fifteen patients underwent cryosurgery followed by lumpectomy (BCS). Median age was 53 years old 5 (33.3%) patients had ductal carcinoma in situ (DCIS), while 10 (66.7%) patients had invasive ductal carcinoma (IDC), of which 5 (50%) patients had luminal type cancers of which 3 (60%) were luminal A and 2 (40%) luminal B, 3 (30%) patients had HER2 enriched invasive carcinoma and 2 (20%) patients had triple negative IDC. Median tumor size was 13mm (Range 8.6-18mm). Seven (46.7%) patients were found to have residual cancer in the post-cryosurgery lumpectomy specimen. All residual cancers were found at the periphery of the cryoablated breast tissue. All breast cancers were otherwise completely ablated centrally as confirmed by routine histopathology, immunochemistry and TUNEL assay for evaluation of cell viability. None of the tumor factors such as tumor biology, as well as surgical factors such as ablation time and iceball size, were associated with risk of residual cancer. None of the 15 patients developed post-operative complications.

CONCLUSION: Residual cancer occurs at the periphery of the cryoablation site, careful pre-operative planning and intra-operative monitoring is crucial to ensure complete cryoablation.}, } @article {pmid36803091, year = {2023}, author = {Maybank, AK and Curtis, H and Topp, T and Barnes, PJ}, title = {Metastatic Mammary Carcinoma Presenting as a Large Cystic Axillary Mass: A Report of an Unusual Case.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {10668969231152574}, doi = {10.1177/10668969231152574}, pmid = {36803091}, issn = {1940-2465}, abstract = {The differential diagnosis of cystic axillary masses is broad and includes intranodal lesions. Cystic metastatic tumor deposits are rare, and have been reported in a few tumor types, most commonly in the head and neck region, but rarely described with metastatic mammary carcinoma. We report a case of a 61-year-old female who presented with a large right axillary mass. Imaging studies revealed a cystic axillary mass and ipsilateral breast mass. She was managed with breast conservation surgery and axillary dissection for invasive ductal carcinoma, no special type, Nottingham grade 2 (21 mm). One of nine lymph nodes contained a cystic nodal deposit (52 mm), which resembled a benign inclusion cyst. Oncotype DX recurrence score for the primary tumor was low (8), conferring a low risk of disease recurrence despite the large size of the nodal metastatic deposit. A cystic pattern of metastatic mammary carcinoma is rare and important to recognize for accurate staging and management decisions.}, } @article {pmid36798680, year = {2023}, author = {Aghajanzadeh, M and Torabi, H and Najafi, B and Talebi, P and Shirini, K}, title = {Intermammary breast cancer: A rare case of cancer with origin of breast cells in an unusual location.}, journal = {SAGE open medical case reports}, volume = {11}, number = {}, pages = {2050313X231154996}, pmid = {36798680}, issn = {2050-313X}, abstract = {The most common type of cancer among the female population is breast cancer. The most common site for the occurrence of breast cancer is the upper outer quadrant; the upper inner quadrant is the second site, and both the lower outer and the lower inner quadrants are in the third place. This problem is rarely seen in the central portion. Intermammary metastasis due to breast cancer is an infrequent finding. This article presents a 62-year-old lady who presented to the surgical ward with intermammary swelling that appeared suddenly 3 months ago. Ultrasound examination showed a hypoechoic micro-lobulated mass with internal vascularity on the chest wall. Although core needle biopsy suspected invasive ductal carcinoma, both right and left axillary lymph nodes were normal and free. The patient was consulted by an oncologist who recommended radiotherapy before surgery and chemotherapy before and after surgery. This study aims to report and discuss a rare case of intermammary cancer with the origin of breast cells without breast and axillary lymph node involvement. Although the intermammary region is an extremely rare location where breast cancer could occur, its management strategy is the same as other breast cancers.}, } @article {pmid36797734, year = {2023}, author = {Arias Ramos, D and Alzate, JA and Moreno Gómez, GA and Hoyos Pulgarín, JA and Olaya Gómez, JC and Cortés Bonilla, I and Vargas Mosquera, C}, title = {Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {13}, pmid = {36797734}, issn = {1476-0711}, mesh = {Humans ; Retrospective Studies ; Cross-Sectional Studies ; *Escherichia coli Infections/drug therapy ; Tertiary Care Centers ; Colombia/epidemiology ; beta-Lactamases/genetics ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; *Bacteremia/drug therapy/microbiology ; }, abstract = {BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.

METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum β-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.

RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58 years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score > 3 points, and not having an infectious disease consultation (IDC).

CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.}, } @article {pmid36797689, year = {2023}, author = {Al-Keilani, MS and Bdeir, R and Elstaty, RI and Alqudah, MA}, title = {Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {158}, pmid = {36797689}, issn = {1471-2407}, support = {20170380//Deanship of scientific research, jordan university of science and technology, Jordan/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Substance P ; Receptors, Neurokinin-1/metabolism ; Ki-67 Antigen/metabolism ; Pyruvate Kinase ; *Triple Negative Breast Neoplasms ; Hormones ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer.

METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder.

RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047).

CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.}, } @article {pmid36788935, year = {2023}, author = {Shenkman, G and Bos, HMW and D'Amore, S and Carone, N}, title = {Mental Health Disparities Between Lesbian Mothers and Heterosexual Parents: the Mediating Role of Positivity.}, journal = {Sexuality research & social policy : journal of NSRC : SR & SP}, volume = {}, number = {}, pages = {1-11}, pmid = {36788935}, issn = {1868-9884}, abstract = {INTRODUCTION: Previous evidence has shown better mental health outcomes for lesbian mothers, in comparison with heterosexual parents. The present study explored the mediating role of positivity (i.e., the tendency to view life with a positive outlook) in determining these mental health differences.

METHODS: Seventy-two Israeli lesbian mothers by donor insemination (from 36 families) were compared with 72 Israeli heterosexual parents by assisted reproduction (without donated gametes; from 36 families) on positivity, life satisfaction, and depressive symptomatology. All parents were cisgender and had at least one child born through assisted reproduction, aged 3-10 years. Data were collected between December 2019 and February 2021.

RESULTS: Mediational analyses indicated that lesbian mothers reported greater positivity, which was, in turn, associated with greater life satisfaction and less depressive symptomatology.

CONCLUSIONS: The results pinpoint the possible protective and strengthening role of positivity for lesbian mothers in the pronatalist and familistic environment of Israel. The research contributes to the literature on the mental health of parents with diverse sexual orientations living outside of the USA and Europe. Policy Implications Policymakers and mental health professional should be knowledgeable about the importance of improving positivity as a strategy for reducing depressive symptomatology and promoting life satisfaction among lesbian mothers. Moreover, policy makers and legislators are called to ease the access of sexual minority individuals to parenthood, as in this population parenthood associates with heightened mental health outcomes.}, } @article {pmid36788122, year = {2023}, author = {Huang, K and Dufresne, M and Baksh, M and Nussbaum, S and Abbaszadeh Kasbi, A and Mohammed, A and Advani, P and Morozov, A and Bagaria, S and McLaughlin, S and Gabriel, E}, title = {How Well Does Non-mass Enhancement Correlate With DCIS/Invasive Cancer?.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348231156776}, doi = {10.1177/00031348231156776}, pmid = {36788122}, issn = {1555-9823}, abstract = {INTRODUCTION: Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology.

METHODS: This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology.

RESULTS: From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT.

CONCLUSIONS: Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach.}, } @article {pmid36787199, year = {2023}, author = {Ochiai, S and Chiba, N and Gunji, T and Kobayashi, T and Sano, T and Tomita, K and Shigoka, M and Tabuchi, S and Hidaka, E and Wakiya, M and Nakatsugawa, M and Kawachi, S}, title = {Efficacy of CT Value Along Portal Vein for Preoperative Prediction of Portal Vein Resection in Pancreatic Head Cancer.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348231156772}, doi = {10.1177/00031348231156772}, pmid = {36787199}, issn = {1555-9823}, abstract = {BACKGROUND: It is important for surgeons to determine whether combined portal vein (PV) resection (PVR) is necessary before surgery. The present study aimed to determine the ability of computed tomography (CT) value along the PV in predicting the necessity for concomitant PVR.

METHODS: A total of 107 consecutive patients who underwent pancreaticoduodenectomy (PD) for invasive ductal carcinoma of the pancreatic head at our institute between September 2007 and September 2020 were reviewed retrospectively. Univariate analysis to predict PVR was performed with preoperative radiological valuables acquired by Synapse Vincent. The resected specimen near the PV or the PV notch was analyzed by histopathological findings.

RESULTS: Only the CT value of the PV was independently associated with PVR (Mann-Whitney U test; P = .045, logistic regression test; P = .039). The outer boundary of the PV was unclear in the cases without pathological PV invasion and PVR due to the development of smooth muscle in the outer membrane of the PV and the proliferation of collagen fibers. The elastic fibers were arranged regularly in the notch portion of the PV in cases wherein PVR was not performed.

DISCUSSION: The CT value along the PV was independently associated with PVR and is the only predictor of PVR. These results were very useful in predicting PVR preoperatively and were histopathologically supportive.}, } @article {pmid36786227, year = {2023}, author = {Salzano, S and Zappullo, I and Senese, VP and Conson, M and Finelli, C and Mikulincer, M and Shaver, PR}, title = {Validation and psychometric properties of the Italian version of the Power Behavioural System Scale.}, journal = {Research in psychotherapy (Milano)}, volume = {26}, number = {1}, pages = {}, pmid = {36786227}, issn = {2239-8031}, abstract = {The power behavioural system is a neurobehavioral system that motivates a person to acquire and control resources that are important for survival and reproductive success. When activated, its function is to protect or restore the sense of power, influence, or dominance. Repeated experiences of failure in achieving this goal may result in hyperactivation or deactivation of power-oriented behaviours (analogous to the secondary strategies observed with respect to the attachment behavioural system). Gaining a reliable and valid measure of hyperactivation and deactivation of the power system can be important for understanding an individual's responses to different social contexts and, in clinical settings, can help the therapist identify the client's difficulties that may undermine the therapeutic process. In the present study, we developed the Italian version of the Power Behavioural System Scale (PBSS), a self-report measure developed by Shaver et al. (2011) to assess individual differences in hyperactivation and deactivation of the power system. Results indicated an adequate fit to the expected two-factor model, and the measure proved to be reliable and had good convergent and structural validity, allowing the quantification of individual differences in power system hyperactivation and deactivation.}, } @article {pmid36781838, year = {2023}, author = {Sekido, N and Matsuoka, M and Takahashi, R and Sengoku, A and Nomi, M and Matsuyama, F and Murata, T and Kitta, T and Mitsui, T}, title = {Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.}, journal = {Spinal cord series and cases}, volume = {9}, number = {1}, pages = {3}, pmid = {36781838}, issn = {2058-6124}, mesh = {Humans ; *Urinary Catheters/adverse effects ; Cross-Sectional Studies ; Urinary Catheterization/adverse effects ; Japan/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Spinal Cord ; }, abstract = {STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.

OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.

SETTING: An internet survey.

METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).

RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.

CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.}, } @article {pmid36777854, year = {2023}, author = {Ma, R and Tang, Z and Wang, J}, title = {PTTG1IP (PBF) is a prognostic marker and correlates with immune infiltrate in ovarian cancer.}, journal = {American journal of translational research}, volume = {15}, number = {1}, pages = {27-46}, pmid = {36777854}, issn = {1943-8141}, abstract = {OBJECTIVE: An oncogenic protein, pituitary tumor transforming gene 1 binding factor (PTTG1IP, also called PBF), has been found to be expressed in various cancers. However, few studies have explored its prognostic significance and biologic function in epithelial ovarian cancer (EOC).

METHODS: Based on the Cancer Genome Atlas (TCGA) database, this study determined the differential expression of PBF at the mRNA level in EOC and normal tissues, which was then verified using real-time PCR and western blotting. Moreover, the Kaplan-Meier method and the Cox regression method were adopted to assess the clinical value of PBF in EOC. A nomogram model was constructed to evaluate the prognostic performance of PBF in EOC. Gene set enrichment analysis (GSEA) was employed to evaluate the signaling and pathway enrichment of PBF in EOC. The association between PBF expression and tumor-infiltrating immune cells (TIICs) in EOC was examined by single-sample GSEA and TIMER.

RESULTS: PBF was significantly higher in EOC than normal tissues as shown through TCGA database, and this result was verified by qRT-PCR and western blotting of EOC tissues and different cell lines. High PBF was associated with tumor size and lymphatic metastasis status. Kaplan-Meier (KM) analysis indicated that high PBF expression correlated with poor prognosis in patients with EOC (P < 0.0001). Moreover, multivariate Cox regression analysis was used to verify that PBF is an independent prognostic factor for EOC. The nomogram model exhibited moderate predictive accuracy and clinical utility in predicting EOC prognosis. The GSEA revealed that the expression of signaling pathways, such DNA damage replication, p53 pathway, Akt phosphorylation pathway, and estrogen-dependent nuclear pathway, were increased in the phenotype with high PBF expression. PBF expression was associated with neutrophil cells, iDC cells, NK cells, and Tem cells.

CONCLUSION: As a prognostic biomarker for EOC, PBF was found to be correlated with immune infiltration, and may therefore be a promising target for immunotherapy for EOC.}, } @article {pmid36769184, year = {2023}, author = {Górnicki, T and Lambrinow, J and Mrozowska, M and Romanowicz, H and Smolarz, B and Piotrowska, A and Gomułkiewicz, A and Podhorska-Okołów, M and Dzięgiel, P and Grzegrzółka, J}, title = {Expression of RBMS3 in Breast Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769184}, issn = {1422-0067}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Breast/metabolism ; *Carcinoma, Ductal, Breast/pathology ; MCF-7 Cells ; RNA, Messenger/genetics ; Cell Line, Tumor ; Trans-Activators/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.}, } @article {pmid36765396, year = {2023}, author = {Sui, Y and Li, S and Fu, XQ and Zhao, ZJ and Xing, S}, title = {Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {109}, pmid = {36765396}, issn = {1479-5876}, mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Janus Kinases/therapeutic use ; *Neoplasms ; Carcinogenesis ; Computational Biology ; RNA, Messenger/metabolism ; }, abstract = {BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.

RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.

CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.}, } @article {pmid36763857, year = {2023}, author = {Langley, RG and Sofen, H and Dei-Cas, I and Reich, K and Sigurgeirsson, B and Warren, RB and Paul, C and Szepietowski, JC and Tsai, TF and Hampele, I and You, R and Charef, P and Papavassilis, C}, title = {Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.}, journal = {The British journal of dermatology}, volume = {188}, number = {2}, pages = {198-207}, doi = {10.1093/bjd/ljac040}, pmid = {36763857}, issn = {1365-2133}, mesh = {Humans ; Quality of Life ; *Nasopharyngitis/chemically induced ; Antibodies, Monoclonal, Humanized/adverse effects ; *Psoriasis/drug therapy ; *Respiratory Tract Infections ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; }, abstract = {BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.

OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.

METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.

RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.

CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.}, } @article {pmid36762811, year = {2023}, author = {Joe, WH and Lee, CY and Kim, CH and Ko, YS and Kim, SP and Kwon, SM}, title = {Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.}, journal = {Brain tumor research and treatment}, volume = {11}, number = {1}, pages = {73-78}, pmid = {36762811}, issn = {2288-2405}, support = {2020R1G1A1013289//National Research Foundation of Korea/Korea ; }, abstract = {Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.}, } @article {pmid36755863, year = {2022}, author = {Zhu, S and Wang, H and Lin, L and Fei, X and Wu, J}, title = {Primary breast osteosarcoma in a patient previously treated for ipsilateral invasive ductal carcinoma: An unusual case report with clinical and genomic features.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1013653}, pmid = {36755863}, issn = {2234-943X}, abstract = {Primary breast osteosarcoma is a rare subtype of breast malignancy with limited clinical evidence, inadequate biological understanding, and unmet treatment consensus. Here, we report an unusual case of primary breast osteosarcoma developing in the same quadrant of the breast 2 years after initial dissection and radiation of invasive ductal carcinoma. Thorough evaluations of imaging and pathology were conducted while genomic alterations of both primary and secondary tumors, as well as peripheral blood samples, were explored through the next-generation sequencing technique. A comprehensive review of the current literature was also performed on this rare malignancy.}, } @article {pmid36754375, year = {2023}, author = {Goubar, A and Martin, FC and Sackley, C and Foster, NE and Ayis, S and Gregson, CL and Cameron, ID and Walsh, NE and Sheehan, KJ}, title = {Development and Validation of Multivariable Prediction Models for In-Hospital Death, 30-Day Death, and Change in Residence After Hip Fracture Surgery and the "Stratify-Hip" Algorithm.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {78}, number = {9}, pages = {1659-1668}, pmid = {36754375}, issn = {1758-535X}, support = {MR/S032819/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Aged ; Hospital Mortality ; *Hip Fractures/surgery ; Algorithms ; England/epidemiology ; }, abstract = {BACKGROUND: To develop and validate the stratify-hip algorithm (multivariable prediction models to predict those at low, medium, and high risk across in-hospital death, 30-day death, and residence change after hip fracture).

METHODS: Multivariable Fine-Gray and logistic regression of audit data linked to hospital records for older adults surgically treated for hip fracture in England/Wales 2011-14 (development n = 170 411) and 2015-16 (external validation, n = 90 102). Outcomes included time to in-hospital death, death at 30 days, and time to residence change. Predictors included age, sex, pre-fracture mobility, dementia, and pre-fracture residence (not for residence change). Model assumptions, performance, and sensitivity to missingness were assessed. Models were incorporated into the stratify-hip algorithm assigning patients to overall low (low risk across outcomes), medium (low death risk, medium/high risk of residence change), or high (high risk of in-hospital death, high/medium risk of 30-day death) risk.

RESULTS: For complete-case analysis, 6 780 of 141 158 patients (4.8%) died in-hospital, 8 693 of 149 258 patients (5.8%) died by 30 days, and 4 461 of 119 420 patients (3.7%) had residence change. Models demonstrated acceptable calibration (observed:expected ratio 0.90, 0.99, and 0.94), and discrimination (area under curve 73.1, 71.1, and 71.5; Brier score 5.7, 5.3, and 5.6) for in-hospital death, 30-day death, and residence change, respectively. Overall, 31%, 28%, and 41% of patients were assigned to overall low, medium, and high risk. External validation and missing data analyses elicited similar findings. The algorithm is available at https://stratifyhip.co.uk.

CONCLUSIONS: The current study developed and validated the stratify-hip algorithm as a new tool to risk stratify patients after hip fracture.}, } @article {pmid36753450, year = {2023}, author = {Taylor, DB and Burrows, S and Dessauvagie, BF and Saunders, CM and Ives, A}, title = {Accuracy and precision of contrast enhanced mammography versus MRI for predicting breast cancer size: how "good" are they really?.}, journal = {The British journal of radiology}, volume = {96}, number = {1144}, pages = {20211172}, pmid = {36753450}, issn = {1748-880X}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/pathology ; Prospective Studies ; Contrast Media ; Mammography/methods ; Magnetic Resonance Imaging/methods ; }, abstract = {OBJECTIVE: To evaluate and compare the accuracy and precision of contrast-enhanced mammography (CEM) vs MRI to predict the size of biopsy-proven invasive breast cancer.

METHODS: Prospective study, 59 women with invasive breast cancer on needle biopsy underwent CEM and breast MRI. Two breast radiologists read each patient's study, with access limited to one modality. CEM lesion size was measured using low-energy and recombined images and on MRI, the first post-contrast series. Extent of abnormality per quadrant was measured for multifocal lesions. Reference standards were size of largest invasive malignant lesion, invasive (PathInvasive) and whole (PathTotal). Pre-defined clinical concordance ±10 mm.

RESULTS: Mean patient age 56 years, 42 (71%) asymptomatic. Lesions were invasive ductal carcinoma 40 (68%) with ductal carcinoma in situ (31/40) in 78%, multifocal in 12 (20%). Median lesion size was 17 mm (invasive) and 27 mm (total), range (5-125 mm). Lin's concordance correlation coefficients for PathTotal 0.75 (95% CI 0.6, 0.84) and 0.71 (95% CI 0.56, 0.82) for MRI and contrast-enhanced spectral mammography (CESM) respectively. Mean difference for total size, 3% underestimated and 4% overestimated, and for invasive 41% and 50% overestimate on MRI and CESM respectively. LOAs for PathTotal varied from 60% under to a 2.4 or almost threefold over estimation. MRI was concordant with PathTotal in 36 (64%) cases compared with 32 (57%) for CESM. Both modalities concordant in 26 (46%) cases respectively.

CONCLUSION: Neither CEM nor MRI have sufficient accuracy to direct changes in planned treatment without needle biopsy confirmation.

ADVANCES IN KNOWLEDGE: Despite small mean differences in lesion size estimates using CEM or MRI, the 95% limits of agreement do not meet clinically acceptable levels.}, } @article {pmid36753185, year = {2019}, author = {Lima-Ribeiro, I and Lima-Ribeiro, I and Da Silva Santa Rosa, JG and Do Céu-Clara Costa, I}, title = {[Healthy eating, schoolchildren perception about themselves].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {21}, number = {3}, pages = {381-386}, doi = {10.15446/rsap.V21n3.54047}, pmid = {36753185}, issn = {2539-3596}, mesh = {Child ; Humans ; *Feeding Behavior ; *Diet, Healthy ; Parents ; Vegetables ; Perception ; Diet ; }, abstract = {OBJECTIVE: To evaluate the perception of schoolchildren between 7-10 years of a public school in Natal-RN about healthy eating.

METHOD: Descriptive study, with quantitative and qualitative approach by focus group interviews with 29 students whose average age was 8.8 years. The analysis was aided by IRAMUTEQ software and supported the concept of perception of Merleau-Ponty.

RESULTS: Children's perception about healthy eating was associated with fresh foods and culinary preparations. We identified concepts acquired at school on the topic, as well as teachers criticizing the consumption of ultra-processed foods. There were reports of predilection for certain school meals and rejection of others. In addition, children have cited the presence of unhealthy foods served at school. Regarding the role of families, parents were cited in the role of guide for a healthy consumption at the same time they encouraged to consumption of processed foods at home or they provided money to buy them. Many children did not consume healthy foods, mainly fruits and vegetables because they consider unpalatable.

CONCLUSION: The perception of children about healthy foods was influenced by school, family and media. Although they possessed sense of what would be a healthy feed, the pleasure in eating processed foods led to unhealthy practices. The findings show the need for a look magnified by the professionals involved in this role to stimulate and drive healthy practices.}, } @article {pmid36752370, year = {2023}, author = {Miceli, R and Gao, Y and Qian, K and Heller, SL}, title = {Predicting Upgrade of Ductal Carcinoma In Situ to Invasive Breast Cancer at Surgery With Ultrafast Imaging.}, journal = {AJR. American journal of roentgenology}, volume = {221}, number = {1}, pages = {34-43}, doi = {10.2214/AJR.22.28698}, pmid = {36752370}, issn = {1546-3141}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Mammography ; Magnetic Resonance Imaging/methods ; Sentinel Lymph Node Biopsy ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND. Biopsy-proven ductal carcinoma in situ (DCIS) lesions are often upgraded to invasive cancer at surgery. Therefore, accurate prediction of the likelihood of invasion is helpful for surgical planning, including the need for sentinel lymph node biopsy (SLNB). OBJECTIVE. The purpose of the present study was to investigate whether kinetic features of clinically available ultrafast MRI (UF-MRI) can predict upgrade of biopsy-proven DCIS to invasive cancer at surgical excision. METHODS. Consecutive patients with biopsy-proven pure DCIS lesions who underwent UF-MRI with conventional dynamic contrast-enhanced MRI (DCE-MRI) and subsequently underwent surgery between August 2019 and January 2021 were identified. Patient and lesion characteristics, biopsy method and pathology, and lesion features on mammography, ultrasound, DCE-MRI, and UF-MRI were assessed to determine predictors of upgrade to invasive cancer. The Fisher exact test and Kruskal-Wallis test were used for association analysis. RESULTS. In 68 patients (median age, 52.0 years; range, 31-79 years) with 68 biopsy-proven pure DCIS lesions, 26 lesions (38%) were upgraded from in situ to invasive cancer. An upgrade of DCIS to invasive cancer was significantly associated with a shorter time to enhancement (TTE) on preoperative UF-MRI (p = .03), with a threshold of 11 seconds providing maximum specificity (50%) and sensitivity (76%) for upgrade. Larger lesion size on DCE-MRI (p = .001) and mammography (p = .04) was also significantly associated with upgrade; an optimal predictive threshold of 4.4 cm on DCE-MRI yielded sensitivity of 88% and specificity of 56%. No other specific variables were significantly associated with upgrade after surgery. Logistic regression of selected features combined with TTE produced a higher AUC (0.85) in predicting upgrade to invasive disease than did each factor alone, but this result was not statistically significant. CONCLUSION. Preoperative UF-MRI TTE and lesion size on DCE-MRI and mammography show potential in predicting upgrade of DCIS to invasive cancer at surgery. CLINICAL IMPACT. UF-MRI provides useful information that can be used in surgical planning, including determination of the need to perform SLNB.}, } @article {pmid36747860, year = {2023}, author = {Ricks-Santi, LJ and Fredenburg, K and Rajaei, M and Esnakula, A and Naab, T and McDonald, JT and Kanaan, Y}, title = {Characterization of GATA3 and Mammaglobin in breast tumors from African American women.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36747860}, support = {R15 CA239100/CA/NCI NIH HHS/United States ; }, abstract = {GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.}, } @article {pmid36742232, year = {2022}, author = {Ghalkhani, E and Akbari, MT and Izadi, P and Mahmoodzadeh, H and Kamali, F}, title = {The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis.}, journal = {Iranian journal of public health}, volume = {51}, number = {12}, pages = {2808-2816}, pmid = {36742232}, issn = {2251-6093}, abstract = {BACKGROUND: A significant part of deaths related to breast cancer is the result of invasion to other organs. It is essential to discover new non-invasive biomarkers to improve anticipation of recurrence risk in breast cancer patients. In this study, the plasma levels of miR-129 and miR-203a were evaluated to investigate their diagnostic potential in breast cancer and its metastasis.

METHODS: In this case-control study, conducted in Tarbiat Modares University, Tehran, Iran, in 2019, Invasive Ductal Carcinoma blood samples were divided into 3 groups based on their stages as I, II/III, IV. Each group contained 30 individuals. We also recruited 30 normal individuals as a control group. Real-Time PCR was conducted to evaluate miR-129 and miR-203a expression levels. The discriminatory ability of the evaluated plasma miRNAs was assessed by ROC (Receiver Operating Characteristic) curves in breast cancer diagnosis and its metastasis.

RESULTS: MiR-129 and miR-203a expression levels were significantly downregulated in breast cancer. Reducing tendency was observed in the mentioned miRNAs from less to more invasive stages. The expression level of miR-129 was decreased in metastatic than non-metastatic patients and it was significantly related to metastasis. A significant association between miR-129 expression level and lymph node status was also observed (P=0.04). Evaluation of ROC curves revealed that miR-129 and miR-203a were able to discriminate breast cancer fairly and poorly respectively. The ability of miR-129 in the diagnosis of breast cancer metastasis was poor.

CONCLUSION: MiR-129 and miR-203a may both act as tumor suppressor miRNAs. Our results need further evidence in a large population to be confirmed as diagnostic markers.}, } @article {pmid36742153, year = {2023}, author = {Liu, W and Wan, Q and Zhou, E and He, P and Tang, L}, title = {LncRNA LINC01833 is a Prognostic Biomarker and Correlates with Immune Infiltrates in Patients with Lung Adenocarcinoma by Integrated Bioinformatics Analysis.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {3965198}, pmid = {36742153}, issn = {1687-8450}, abstract = {Due to the absence of accurate tools for early detection and successful treatment, lung adenocarcinoma (LUAD) is one of the most aggressive tumors with high morbidity and mortality globally. It is absolutely necessary to investigate the process behind its development and search for new biomarkers that could aid in the early detection of LUAD. There is a correlation between the immune microenvironment of the tumor and the prognosis of lung cancer as well as the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been identified as potential prognostic biomarkers linked to immunological activities. In this study, we identified 1 downregulated lncRNA and 76 upregulated lncRNAs in LUAD samples from TCGA datasets. Among the 77 dysregulated lncRNAs, our attention focused on lncRNA LINC01833 (LINC01833). When compared with nontumor specimens, the level of expression of LINC01833 was shown to be significantly elevated in LUAD samples. In addition, the data of the ROC study revealed that LUAD patients with high LINC01833 expression had an AUC value of 0.840 (95% confidence interval: 0.804 to 0.876). There was a correlation between high LINC01833 expression and an advanced clinical stage. Patients who had a high expression of LINC01833 were shown to have a lower overall survival rate (p < 0.001) and a lower disease-specific survival rate (p = 0.004) in comparison to patients who were in the low LINC01833 group, according to the data on survival. In addition, the results of the multivariate analysis revealed that high LINC01833 expression was an independent predictor of poor survival in LUAD. Moreover, the immune analysis revealed that we found that the expression of LINC01833 was positively associated with Th2 cells, aDC, and Tgd, while negatively associated with Mast cells, Tcm, Eosinophils, iDC, DC, Tem, Th17 cells, and pDC. Overall, our data point to the possibility that the unique lncRNA LINC01833 might be employed as a diagnostic and prognostic marker, and as a result, it has a significant impact on clinical practice.}, } @article {pmid36738975, year = {2023}, author = {Okubo, Y and Sato, S and Hasegawa, C and Koizumi, M and Suzuki, T and Yamamoto, Y and Yoshioka, E and Ono, K and Washimi, K and Yokose, T and Kishida, T and Miyagi, Y}, title = {Cribriform pattern and intraductal carcinoma of the prostate can have a clinicopathological impact, regardless of their percentage and/or number of cores.}, journal = {Human pathology}, volume = {135}, number = {}, pages = {99-107}, doi = {10.1016/j.humpath.2023.01.008}, pmid = {36738975}, issn = {1532-8392}, mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/pathology ; Prostate/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Lymphatic Metastasis/pathology ; *Prostatic Neoplasms/surgery/pathology ; Prostatectomy ; Neoplasm Grading ; }, abstract = {Cribriform pattern and intraductal carcinoma of the prostate (IDC-P) are widely accepted as poor prognostic factors in prostate cancer. However, it remains unclear to what extent the presence of these morphological features in prostate biopsy specimens, as diagnosed by hematoxylin-eosin-stained specimens only, affects the clinicopathological impact. In this study, we summarized the characteristics of the cribriform pattern and IDC-P in 850 prostate biopsy cases. The results showed a statistically significant increase in the incidence of cribriform pattern and IDC-P as grade group (GG) increased (especially in cases ≥ GG4, Chi-square test P < 0.001). The independent risk factors for cribriform pattern and IDC-P in biopsy specimens in the multivariate logistic regression analysis were the former GG, presence of IDC-P, lesion length of the highest GG core, latter GG, presence of the cribriform pattern, number of biopsies obtained, and number of highest GG core. Overall, 125 cases in which radical prostatectomy was conducted after biopsy were selected for further analysis. Multivariate logistic regression analysis using biopsy and surgical specimens confirmed that the presence of the cribriform pattern and IDC-P in biopsy specimens were independent risk factors for lymph node metastasis (odds ratios [95% confidence interval] were 6.54 [1.15-37.05] for the cribriform pattern and 23.71 [1.74-322.42] for IDC-P). The presence of the cribriform pattern and/or IDC-P in a biopsy specimen was a significant factor, even if only partially present, indicating lymph node metastasis. However, further validation is required to predict poor prognostic factors more accurately.}, } @article {pmid36733163, year = {2022}, author = {Oshima, K and Mitsuyoshi, A and Kikumori, K and Hori, A and Yanagawa, T and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of Locally Advanced Breast Cancer That Responded to Paclitaxel plus Bevacizumab and Underwent Radical Surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1645-1647}, pmid = {36733163}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Paclitaxel ; Bevacizumab/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; }, abstract = {The patient is a 69-year-old female. She was aware of a right breast mass about a year ago, but left it alone. In March 2021, she visited our hospital with a 11 cm mass occupying the right breast and self-destruction due to skin invasion. The diagnosis of invasive ductal carcinoma of the breast(ER-positive, PgR-positive, HER2-negative), cT4bN1M0, Stage ⅢB was made, and preoperative chemotherapy was decided. We expected a high response rate for bevacizumab(Bv)because it was predicted that the skin defect would increase at surgical resection if a response to chemotherapy was not achieved, and in April 2021, paclitaxel(PTX)plus Bv therapy was initiated. After 4 courses, the mass had shrunk to 5 cm and a marked response had been achieved. However, she was unable to continue the treatment due to peripheral neuropathy. Therefore, considering the period of delayed wound healing due to Bv, we decided on AC therapy followed by surgery. In December 2021, Bt plus Ax was performed and the wound could be closed without skin grafting. Since PTX plus Bv therapy is expected to have a high response rate, we considered it to be one of the effective treatment options for locally advanced breast cancer.}, } @article {pmid36733146, year = {2022}, author = {Hojo, S and Yoshioka, S and Wakabayashi, Y}, title = {[A Case Performed Mastectomy to Tumor Progression of Breast Cancer Omitting Surgery after Neoadjuvant Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1594-1596}, pmid = {36733146}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Mastectomy ; Neoadjuvant Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; }, abstract = {We report a case performed mastectomy to tumor progression of breast cancer omitting surgery after neoadjuvant chemotherapy. A 62-year-old female patient visited our hospital for left breast tumor. A tumor of the size of 26×24 mm was found at between lower and upper outer quadrant, and we diagnosed it as breast cancer(cT1, cN2, M0, Stage ⅢA, ER positive/HER2 positive). Neoadjuvant chemotherapy by triweekly trastuzumab and weekly paclitaxel followed by EC chemotherapy were performed. However, she rejected surgery after neoadjuvant chemotherapy, and although we consequently restarted a regimen of triweekly trastuzumab which she also refused to continue after 9 cycles. 32 months later, she noticed induration on her left breast, and we diagnosed it as tumor progression of breast cancer. After obtaining informed consent, we performed total mastectomy and axillary lymph node dissection. Histological diagnosis revealed invasive ductal carcinoma, ER negative/HER2 positive, and no axillary lymph node metastasis. So far omission of surgery after neoadjuvant chemotherapy to breast cancer is not defined yet, and we expect early definition of evidence.}, } @article {pmid36733112, year = {2022}, author = {Satoh, E and Hara, M and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Case of Recurrent Breast Cancer with Multiple Bone Metastasis Effectively Treated by CDK4/6 Inhibitor in Addition to Aromatase Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {13}, pages = {1491-1493}, pmid = {36733112}, issn = {0385-0684}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Aromatase Inhibitors/therapeutic use ; Letrozole ; Mastectomy ; Lymph Node Excision ; Cyclin-Dependent Kinase 4 ; }, abstract = {We report a case of recurrent breast cancer with multiple bone metastasis in a 62-year-old woman. Her breast cancer (invasive ductal carcinoma, T2N0M0, Stage ⅡA)was resected in 2001(partial mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(UFT)and irradiation to her left remnant breast. In February 2018, she complained of severe pain in right femoral joint and hip. CT scan showed a left cystic breast tumor(17 cm)and multiple bone metastasis. The core needle biopsy of the costal bone lesion and left mastectomy were performed. These pathological findings were recurrence of the breast cancer(ER+). The endocrine therapy(exemestane, aromatase inhibitor), the administration of denosumab and irradiation to painful bone lesions were performed, but it did not suppress tumor progression. The treatment of letrozole plus palbociclib(CDK4/6 inhibitor)were continued for 3 months from May 2018, and this therapy made her bone lesions smaller, but palbociclib were stopped due to its severe neutropenia. After that, the single administration of letrozole was continued, but the tumor marker did not become normal. In February 2019, abemaciclib was administered in addition to letrozole. One year later, her symptoms improved and her bone metastases have showed partial response.}, } @article {pmid36730303, year = {2023}, author = {Chang, H and Hu, T and Hu, J and Ding, T and Wang, Q and Cheng, J}, title = {Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {883-887}, pmid = {36730303}, issn = {1473-5741}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Trastuzumab ; Receptor, ErbB-2/metabolism ; *Liver Neoplasms/drug therapy/etiology ; }, abstract = {Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.}, } @article {pmid36729856, year = {2023}, author = {Li, J and Lu, Q and Zhou, H and Xu, F and Huang, J and Hong, R and Wang, S}, title = {Significant response to margetuximab in Chinese HER2-positive metastatic breast cancer patient who progressed after second-line targeted therapy.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {892-895}, pmid = {36729856}, issn = {1473-5741}, mesh = {Female ; Humans ; Antibodies, Monoclonal/therapeutic use ; *Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/pathology ; East Asian People ; Receptor, ErbB-2 ; Trastuzumab ; }, abstract = {Activation of the antibody-dependent cellular cytotoxicity is one of the key mechanisms of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody treatment. Margetuximab is a fragment C (Fc)-modified chimeric anti-HER2 immunoglobulin G1 monoclonal antibody that shares epitope specificity with trastuzumab. In this case, we reported that margetuximab plus chemotherapy was effective as later-line therapy in a postmenopausal Chinese woman with metastatic diseases, who was diagnosed with estrogen receptor -, progesterone receptor (PR)-, HER2+ invasive ductal carcinoma. This patient used paclitaxel-albumin plus trastuzumab and pertuzumab as the first-line therapy with progression-free survival (PFS) of 14 months, and pyrotinib in combined with vinorelbine as the second-line therapy with a PFS of 17 months. Then she received margetuximab plus capecitabine as the third-line treatment, the metastatic lesions in the liver were obviously shrunk, indicating clinical partial response and the PFS was 7 months. This case revealed that margetuximab plus chemotherapy may be an appropriate option for the patients who progressed after treating with anti-HER2 monoclonal antibodies and pyrotinib.}, } @article {pmid36715845, year = {2023}, author = {Kada Mohammed, S and Billa, O and Ladoire, S and Jankowski, C and Desmoulins, I and Poillot, ML and Coutant, C and Beltjens, F and Dabakuyo, S and Arnould, L}, title = {HER2-positive invasive lobular carcinoma: a rare breast cancer which may not necessarily require anti-HER2 therapy. A population-based study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {3}, pages = {343-353}, pmid = {36715845}, issn = {1880-4233}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular ; *Carcinoma, Ductal, Breast ; Treatment Outcome ; Disease-Free Survival ; }, abstract = {BACKGROUND: HER2-positive (HER2 +) invasive lobular breast cancer (ILC) is rare and poorly characterised. In particular, patient outcomes compared to those associated with HER2 + invasive ductal cancer (IDC) and HER2-negative (HER2 -) ILC, as well as the benefits of anti-HER2 therapy, are not well established.

METHODS: We analysed the data from the Côte d'Or Registry of Breast and Gynaecological Cancers (France) for all patients diagnosed with early-stage HER2 + ILC (62 cases), HER2 + IDC (833 cases) and HER2 - ILC (685 cases) between 1998 and 2015 to compare overall and disease-free survival (OS and DFS) between these groups in correlation with anti-HER2 therapy.

RESULTS: ILCs were associated with older age, larger tumours, lower histological grades, higher hormonal receptor positivity rates and multifocality, and more common endocrine therapy. OS and DFS between the three groups did not differ. We found that anti-HER2 therapy was associated with a survival benefit in patients with HER2 + IDC. In contrast, the survival of HER2 + ILC patients was not improved by anti-HER2 treatment, remaining close to that of HER2 - ILC patients.

CONCLUSION: HER2 + ILC seems not to be associated with better outcomes than HER2 + IDC but may not differ from HER2 - ILC in terms of survival.}, } @article {pmid36708642, year = {2023}, author = {Maggi, G and Vitale, C and Cerciello, F and Santangelo, G}, title = {Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.}, journal = {Sleep medicine reviews}, volume = {68}, number = {}, pages = {101759}, doi = {10.1016/j.smrv.2023.101759}, pmid = {36708642}, issn = {1532-2955}, mesh = {Humans ; *REM Sleep Behavior Disorder/etiology/complications ; *Parkinson Disease/complications/epidemiology/drug therapy ; Wakefulness ; *Sleep Initiation and Maintenance Disorders/epidemiology/complications ; Quality of Life ; Prevalence ; Sleep ; *Disorders of Excessive Somnolence/epidemiology/diagnosis ; *Sleep Wake Disorders ; }, abstract = {Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.}, } @article {pmid36703942, year = {2022}, author = {Zarchi, G and Sherman, M and Gady, O and Herzig, T and Idan, Z and Greenbaum, D}, title = {Blockchains as a means to promote privacy protecting, access availing, incentive increasing, ELSI lessening DNA databases.}, journal = {Frontiers in digital health}, volume = {4}, number = {}, pages = {1028249}, pmid = {36703942}, issn = {2673-253X}, abstract = {Not all blockchains are created equal, and many cannot accommodate all of the primary characteristics of big data: Variety, Velocity, Volume and Veracity. Currently, public blockchains are slow and clunky, it can be expensive to keep up with the velocity of genomic data production. Further, the transparent and universally accessible nature of public blockchain doesn't necessarily accommodate all of the variety of sequence data, including very private information. Bespoke private permissioned blockchains, however, can be created to optimally accommodate all of the big data features of genomic data. Further, private permissioned chains can be implemented to both protect the privacy and security of the genetic information therein, while also providing access to researchers. An NFT marketplace associated with that private chain can provide the discretized sale of anonymous and encrypted data sets while also incentivizing individuals to share their data through payments mediated by smart contracts. Private blockchains can provide a transparent chain of custody for each use of the customers' data, and validation that this data is not corrupted. However, even with all of these benefits there remain some concerns with the implementation of this new technology including the ethical, legal and social implications typically associated with DNA databases.}, } @article {pmid36703131, year = {2023}, author = {Shenkman, G and Itzhak, SB}, title = {Estimated likelihood of parenthood among sexual minority individuals associates with interpersonal vulnerability and traumatic outlook.}, journal = {Journal of reproductive and infant psychology}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/02646838.2023.2171563}, pmid = {36703131}, issn = {1469-672X}, abstract = {BACKGROUND: Lesbian women and gay men (LG) tend to report lower levels of parenthood aspiration than their heterosexual counterparts. While several variables have been suggested to explain this phenomenon, no study has investigated the potential mediating role of interpersonal vulnerability and subjective traumatic outlook in the association between sexual orientation and the estimated likelihood of parenthood.

OBJECTIVE: To investigate whether interpersonal vulnerability and subjective traumatic outlook mediate the association between sexual orientation and a lower estimated likelihood of parenthood.

METHODS: A sample of 435 childfree, cisgender Israeli participants, aged 18-49 years (M = 27.82, SD = 4.47), were recruited through convenience sampling. 192 participants self-reported as LG (64 lesbian women and 128 gay men). Participants completed online questionnaires assessing their estimated likelihood of parenthood, interpersonal vulnerability, and subjective traumatic outlook. Mediation analyses were performed using the PROCESS macro.

RESULTS: LG individuals reported a lower estimated likelihood of parenthood than their heterosexual counterparts. Interpersonal vulnerability and subjective traumatic outlook significantly mediated the association between sexual orientation and a lower estimated likelihood of parenthood.

CONCLUSIONS: Despite improvement in the socio-political climate relating to sexual minority rights and access to fertility technologies, LG individuals are still more likely to report a lower estimated likelihood of parenthood in comparison to heterosexual individuals. Moreover, this gap appears to be partially mediated by interpersonal vulnerability and subjective traumatic outlook. The results contribute to the growing body of international research exploring family formation among sexual minority individuals and are relevant for researchers, clinicians, and policymakers.}, } @article {pmid36694444, year = {2023}, author = {Da Prat, V and Galli, L and Cichero, P and Castiglioni, B and Oltolini, C and Tassan Din, C and Andolina, A and Bruzzesi, E and Poli, A and Moro, M and Mancini, N and Clementi, M and Tresoldi, M and Castagna, A and Scarpellini, P and Ripa, M}, title = {Antibiotic appropriateness for Gram-negative bloodstream infections: impact of infectious disease consultation.}, journal = {Infectious diseases (London, England)}, volume = {55}, number = {4}, pages = {255-262}, doi = {10.1080/23744235.2023.2169345}, pmid = {36694444}, issn = {2374-4243}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; Retrospective Studies ; *Bacteremia/diagnosis ; Referral and Consultation ; *Sepsis/drug therapy ; *Communicable Diseases/drug therapy ; *Gram-Negative Bacterial Infections ; }, abstract = {BACKGROUND: We investigated the role of infectious disease consultation (IDC) on therapeutic appropriateness in Gram-negative bloodstream infections (GNBSIs) in a setting with a high proportion of antibiotic resistance. Secondary outcomes were in-hospital mortality and the impact of rapid diagnostic tests (RDTs).

METHODS: Retrospective study on hospitalised patients with GNBSIs. Therapy was deemed appropriate if it had the narrowest spectrum considering infection and patients' characteristics. Interventional-IDC (I-IDC) group included patients with IDC-advised first appropriate or last non-appropriate therapy. Time to first appropriate therapy and survival were evaluated by Kaplan-Meier curves. Factors associated with therapy appropriateness were assessed by multivariate Cox proportional-hazard models.

RESULTS: 471 patients were included. High antibiotic resistance rates were detected: quinolones 45.5%, third-generation cephalosporins 37.4%, carbapenems 7.9%. I-IDC was performed in 31.6% of patients (149/471), RDTs in 70.7% (333/471). The 7-day probability of appropriate treatment was 91.9% (95% confidence interval [95%CI]: 86.4-95.8%) vs. 75.8% (95%CI: 70.9-80.4%) with and without I-IDC, respectively (p-value = 0.0495); 85.5% (95%CI: 81.3-89.1%) vs. 69.4% (95%CI: 61.3-77.2%) with and without RDTs, respectively (p-value = 0.0023). Compared to RDTs alone, the combination with I-IDC was associated with a higher proportion of appropriate therapies at day 7: 81.9% (95%CI: 76.4-86.7%) vs. 92.6% (95%CI: 86.3-96.7%). At multivariate analysis, I-IDC and RDTs were associated with time to first appropriate therapy [adjusted hazard-ratio 1.292 (95%CI: 1.014-1.647) and 1.383 (95%CI: 1.080-1.771), respectively], with no impact on mortality.

CONCLUSIONS: In a setting with a high proportion of antibiotic resistance, IDC and RDTs were associated with earlier prescription of appropriate therapy in GNBSIs, without impact on mortality.}, } @article {pmid36693540, year = {2023}, author = {Allegrini, M and Gaillard, C and Brousse, S and Levêque, J and Nyangoh-Timoh, K}, title = {A chyle leak following a tumorectomy and an axillary sentinel lymph node dissection: Case report.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {52}, number = {3}, pages = {102544}, doi = {10.1016/j.jogoh.2023.102544}, pmid = {36693540}, issn = {2468-7847}, mesh = {Female ; Humans ; Aged ; Sentinel Lymph Node Biopsy ; Axilla/pathology ; *Chyle ; Lymph Node Excision ; *Breast Neoplasms/pathology ; }, abstract = {A chyle leak following a tumorectomy is a rare complication of surgery for breast cancer. We report a case of chylous leakage after axillary sentinel lymph node dissection. A 78-year-old woman with a left breast invasive ductal carcinoma underwent a breast-conserving surgery and had two sentinel lymph nodes removed. Ten days after surgery she came back with a swelling the left breast and the axilla, the drainage fluid was "milky". She underwent a second surgery for positive margins, during which time we did a mass ligature in the axilla and placed a drain that was remove when it wasn't productive anymore.}, } @article {pmid36684641, year = {2023}, author = {Tuan, HX and Duc, NM and Huy, NA and Tri, CM and Quyen, HD and Truc, BT and Trung, NT and Dieu, AN and Dung, PX}, title = {A rare case of breast invasive cribriform carcinoma.}, journal = {Radiology case reports}, volume = {18}, number = {3}, pages = {1049-1052}, pmid = {36684641}, issn = {1930-0433}, abstract = {Although invasive ductal carcinoma accounts for 75% of all primary breast cancers diagnosed, there are other, more uncommon kinds, including invasive cribriform carcinoma (ICC). Invasive cribriform carcinoma has 2 subtypes: pure and mixed. Ultrasonography and magnetic resonance imaging are the best imaging methods for assessing the characteristics of breast ICC (MRI). Our goal in this article was to report a rare instance of breast ICC in a 38-year-old Vietnamese woman. During a clinical examination, a spherical mass in the left breast without ipsilateral axillary lymph nodes was seen. On ultrasonography, the lesion was classified as BI-RADS 4C. The lesion was with an apparent diffusion coefficient value of 0.46 × 10[-3] mm[2]/s. Lesion showed a quick initial increase on dynamic T1-weighted imaging with contrast enhancement, followed by a wash-out in the delayed phase. The final histopathological findings confirmed the presence of ICC.}, } @article {pmid36684123, year = {2022}, author = {Li, B and Liu, J and Wu, G and Zhu, Q and Cang, S}, title = {Evaluation of adjuvant therapy for T1-2N1miM0 breast cancer without further axillary lymph node dissection.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {905437}, pmid = {36684123}, issn = {2296-875X}, abstract = {BACKGROUND: For breast cancer (BC) with sentinel lymph node micrometastases (SLNMs), there are limited data to guide the selection of postoperative adjuvant therapy. This study aimed to identify target populations who might benefit most from adjuvant therapy and examine prognostic factors among patients with T1-2N1miM0 BC with one or two SLNMs who underwent sentinel lymph node biopsy (SLNB) alone.

METHODS: There were 7,423 patients diagnosed with T1-2N1miM0 BC between 2010 and 2015, and patients with one or two SLNMs were extracted from the Surveillance, Epidemiology, and End Results database. All the patients underwent SLNB alone without further axillary lymph node dissection, and they were stratified according to adjuvant therapy. The statistical significance of categorical variables was analyzed using the χ [2] test. Univariable and multivariable Cox analyses were used to analyze characteristics predictive of Breast-cancer-specific survival and overall survival (OS). Kaplan-Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments.

RESULTS: Adjuvant chemotherapy and radiotherapy improved 5-year OS rates. Multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and absence of radiotherapy were poor prognostic factors for OS. Patients who received breast-conserving surgery (BCS), and those with invasive ductal carcinoma (IDC), luminal A, luminal B, or basal-like subtype, and T1c or T2 stage benefited from adjuvant radiotherapy. Patients who received BCS, and those with IDC, luminal A subtype, and T1b, T1c, or T2 stage benefited from adjuvant chemotherapy.

CONCLUSION: Our findings provide a clinical evaluation of treatment choice after surgery, which may help clinicians make individualized clinical decisions.}, } @article {pmid36678422, year = {2023}, author = {Feredj, E and Audureau, E and Boueilh, A and Fihman, V and Fourati, S and Lelièvre, JD and Gallien, S and Grimbert, P and Matignon, M and Melica, G}, title = {Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36678422}, issn = {2076-0817}, abstract = {BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.

METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.

RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.}, } @article {pmid36674966, year = {2023}, author = {Hölken, JM and Teusch, N}, title = {The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674966}, issn = {1422-0067}, support = {281A308C18.//Federal Ministry of Food and Agriculture/ ; }, mesh = {Humans ; Cell Line ; *Dendritic Cells/metabolism ; Cell Differentiation ; }, abstract = {We have implemented an improved, cost-effective, and highly reproducible protocol for a simple and rapid differentiation of the human leukemia monocytic cell line THP-1 into surrogates for immature dendritic cells (iDCs) or mature dendritic cells (mDCs). The successful differentiation of THP-1 cells into iDCs was determined by high numbers of cells expressing the DC activation markers CD54 (88%) and CD86 (61%), and the absence of the maturation marker CD83. The THP-1-derived mDCs are characterized by high numbers of cells expressing CD54 (99%), CD86 (73%), and the phagocytosis marker CD11b (49%) and, in contrast to THP-1-derived iDCs, CD83 (35%) and the migration marker CXCR4 (70%). Treatment of iDCs with sensitizers, such as NiSO4 and DNCB, led to high expression of CD54 (97%/98%; GMFI, 3.0/3.2-fold induction) and CD86 (64%/96%; GMFI, 4.3/3.2-fold induction) compared to undifferentiated sensitizer-treated THP-1 (CD54, 98%/98%; CD86, 55%/96%). Thus, our iDCs are highly suitable for toxicological studies identifying potential sensitizing or inflammatory compounds. Furthermore, the expression of CD11b, CD83, and CXCR4 on our iDC and mDC surrogates could allow studies investigating the molecular mechanisms of dendritic cell maturation, phagocytosis, migration, and their use as therapeutic targets in various disorders, such as sensitization, inflammation, and cancer.}, } @article {pmid36671532, year = {2023}, author = {Yang, Y and Luo, D and Gao, W and Wang, Q and Yao, W and Xue, D and Ma, B}, title = {Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671532}, issn = {2218-273X}, support = {81602337//National Natural Science Foundation of China/ ; 81702564//National Natural Science Foundation of China/ ; 81570579//National Natural Science Foundation of China/ ; UNPYSCT-2017062//Education Department of Heilongjiang Province/ ; LH2021H050//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Ferroptosis/genetics ; Algorithms ; Cell Death ; Iron ; *Carcinoma, Ductal ; }, abstract = {Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.}, } @article {pmid36655741, year = {2023}, author = {Zavaglio, F and Rivela, F and Cassaniti, I and Arena, F and Gabanti, E and Asti, AL and Lilleri, D and Rampino, T and Baldanti, F and Gregorini, M}, title = {ELISPOT assays with pp65 peptides or whole HCMV antigen are reliable predictors of immune control of HCMV infection in seropositive kidney transplant recipients.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28507}, pmid = {36655741}, issn = {1096-9071}, mesh = {Humans ; Cytomegalovirus ; Enzyme-Linked Immunospot Assay ; CD8-Positive T-Lymphocytes ; *Kidney Transplantation ; *Cytomegalovirus Infections ; Antigens, Viral ; Antiviral Agents/therapeutic use ; Cytokines ; }, abstract = {Human cytomegalovirus (HCMV) infection represents a major complication for solid organ transplant recipients. The aim of this study was to verify if the measurement of HCMV-specific T-cells could help to identify patients protected against HCMV disease cytokine flow cytometry using infected dendritic cells as stimulus (CFC-iDC, which discriminates between CD4[+] and CD8[+] T cells), and ELISPOT, using infected cell lysate (ELISPOT-iCL) or pp65 (ELISPOT-pp65) as stimulus, were adopted. Among the 47 kidney transplant recipients (KTR) enrolled, 29 had a self-resolving HCMV infection (Controllers) and 18 required antiviral treatment (Non-Controllers). HCMV-specific T-cell frequency at the peak of HCMV infection identified Controllers and Non-Controllers, although the diagnostic performance of CD8[+] CFC-iDC (area under the curve [AUC] of the receiver-operator characteristic curve: 0.65) was lower than that of CD4[+] CFC-iDC (AUC: 0.83), ELISPOT-iCL (AUC: 0.83) and ELISPOT-pp65 (AUC: 0.80). CFC-iDC detected a protective immune reconstitution significantly earlier (median time: 38 days) than ELISPOT-iCL and ELISPOT-pp65 (median time: 126 and 133 days, respectively). Time to protective immune reconstitution in Non-Controllers was significantly longer than in Controllers with the ELISPOT and the CD4[+] CFC-iDC assays, but not with CD8[+] CFC-iDC. The majority of patients did not require antiviral treatment after protective immune reconstitution, with the exception of five patients according to CFC-iDC assay, one patient according to ELISPOT-iCL assay and three patients according to ELISPOT-pp65 assay. Monitoring the HCMV-specific immunological reconstitution with is effective in discriminating KTR at risk of or protected from HCMV disease and the ELISPOT assays are suitable for implementation in the clinical setting.}, } @article {pmid36653542, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {5}, pages = {1607-1612}, pmid = {36653542}, issn = {1590-3478}, mesh = {Humans ; Psychometrics ; *Depression/diagnosis/etiology ; *Parkinson Disease/complications/diagnosis/psychology ; Quality of Life ; Reproducibility of Results ; Psychiatric Status Rating Scales ; }, abstract = {INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort.

MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index.

RESULTS: The BDI-II proved to be internally consistent (Cronbach's α = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50.

CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.}, } @article {pmid36645627, year = {2023}, author = {Yashima, Y and Fujioka, T and Kubota, K and Mori, M and Sato, A and Oda, G and Nakagawa, T and Onishi, I and Tanaka, M and Tateishi, U}, title = {Comparison of the clinical and pathological characteristics of ultrasound-guided biopsy for breast masses and non-mass lesions between 16-gauge spring-loaded core needle biopsy and 12-gauge spring-loaded vacuum-assisted biopsy.}, journal = {Journal of medical ultrasonics (2001)}, volume = {50}, number = {2}, pages = {205-212}, pmid = {36645627}, issn = {1613-2254}, mesh = {Humans ; Female ; Biopsy, Large-Core Needle/methods ; Retrospective Studies ; *Breast/diagnostic imaging/pathology ; Image-Guided Biopsy/methods ; Ultrasonography, Interventional/methods ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {PURPOSE: To retrospectively compare the clinical and pathological characteristics of breast masses and non-mass lesions that underwent ultrasound (US)-guided 16-gauge spring-loaded core needle biopsy (CNB) or 12-gauge spring-loaded vacuum-assisted biopsy (VAB).

METHODS: We retrospectively compared the results from US-guided diagnostic breast biopsy performed with a 16-gauge CNB (Magnum™) or a 12-gauge VAB (Celero[®]). The patients' backgrounds and pathological features for each device were examined.

RESULTS: In 453 patients with 500 lesions, 373 lesions underwent CNB and 127 underwent VAB. The positive biopsy rate (positive predictive value 3) was significantly higher for VAB (92/127; 72.4%) than for CNB (231/373; 61.9%) (P = 0.032). Non-mass lesions were biopsied more frequently with VAB (57/127; 47.4%) than with CNB (27/378; 7.14%) (P = 0.000). The upgrade rate from high-risk to malignant lesions was significantly higher for CNB (5/19; 26.3%) than for VAB (1/8; 12.5%) (P = 0.043). There were five (1.34%) specimen failures with CNB and one (0.78%) with VAB, 18 (4.82%) re-biopsies with CNB and three (2.36%) with VAB, and 11/21 (52.4%) upgrades from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) with CNB and 11/30 (36.7%) with VAB. Although these rates tended to be higher with CNB than with VAB, the difference was not significant.

CONCLUSION: Although VAB had a significantly higher rate of non-mass lesion biopsies, the upgrade rate from high-risk to malignant lesions was significantly lower for VAB than for CNB. US-guided 12-gauge spring-loaded VAB may be more appropriate for biopsy of non-mass lesions.}, } @article {pmid36644191, year = {2022}, author = {Zuo, C and Xie, J}, title = {Mixed primary mucinous cystadenocarcinoma and invasive ductal carcinoma of the breast: a case report and literature review.}, journal = {Translational cancer research}, volume = {11}, number = {12}, pages = {4455-4464}, pmid = {36644191}, issn = {2219-6803}, abstract = {BACKGROUND: Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma (IDC) is the most common breast malignancy. Only 31 cases of the breast MCA have been reported in the English literature, and the coexistence of MCA and IDC in the breast are rare.

CASE DESCRIPTION: Here, we describe a 61-year-old postmenopausal woman with no family history of breast cancer or other breast-related diseases, who presented with a palpable mass in her left breast lasting for 2 months. On ultrasonography examination, the tumor was a cystic-solid lesion with clear boundary. Magnetic resonance imaging (MRI) showed a mass with low signal intensity on T1 weighted imaging and high signal intensity on T2 weighted imaging. Intraoperative frozen sections revealed metastatic tumor cells in one sentinel lymph node (1/4). She then underwent left modified radical mastectomy with axillary dissection. The post-operative pathological examination showed the tumor consisted mostly of MCA (60%), with a small proportion of intermediate-grade IDC. The MCA had a well-demarcated cystic structure with papillary projections and abundant mucoid material. The epithelium lining cystic spaces was tall columnar, with mucin-producing cells that had basally located nuclei. The degree of cytological atypia varied considerably. Axillary lymph nodes were normal (0/15). The MCA was triple-negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, and positive for CK7 but negative for CK20. Through next-generation sequencing, no mutations in the BRCA1 and BRCA2 genes were identified in our case, which was not highlighted in prior cases. After surgery, the patient underwent eight cycles of chemotherapy, and she has been disease-free during the 10-month follow-up. In addition to detailing this instance of mixed MCA and IDC of the breast, we reviewed relevant literature and compare our findings with other patients who had breast MCAs.

CONCLUSIONS: Our results improved the understanding of mixed MCA and IDC, especially MCA, and provided a basis for its diagnosis and differential diagnosis from other metastatic diseases.}, } @article {pmid36641657, year = {2022}, author = {Manginstar, C and Oley, MH and Oley, MC and Merung, M and Langi, FLFG and Kepel, BJ and Rusli, LV and Islam, AA and Faruk, M}, title = {Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {481-487}, doi = {10.3233/BD-229004}, pmid = {36641657}, issn = {1558-1551}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Neoadjuvant Therapy ; Prospective Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use ; Indonesia ; Hypoxia ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.

METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).

RESULTS: Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019).

CONCLUSIONS: There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.}, } @article {pmid36641655, year = {2022}, author = {Kridis, WB and Feki, A and Khmiri, S and Toumi, N and Chaabene, K and Daoud, J and Ayedi, I and Khanfir, A}, title = {Prognostic factors in inflammatory breast cancer: A single-center study.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {461-469}, doi = {10.3233/BD-220034}, pmid = {36641655}, issn = {1558-1551}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics ; Hormones ; *Inflammatory Breast Neoplasms/diagnosis/genetics ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.

METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.

RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.

CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.}, } @article {pmid36641174, year = {2023}, author = {Moghaddam, FD and Heidari, G and Zare, EN and Djatoubai, E and Paiva-Santos, AC and Bertani, FR and Wu, A}, title = {Carbohydrate polymer-based nanocomposites for breast cancer treatment.}, journal = {Carbohydrate polymers}, volume = {304}, number = {}, pages = {120510}, doi = {10.1016/j.carbpol.2022.120510}, pmid = {36641174}, issn = {1879-1344}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy ; Polymers/therapeutic use/chemistry ; *Nanocomposites/therapeutic use/chemistry ; Carbohydrates ; }, abstract = {Breast cancer is known as the most common invasive malignancy in women with the highest mortality rate worldwide. This concerning disease may be presented in situ (relatively easier treatment) or be invasive, especially invasive ductal carcinoma which is highly worrisome nowadays. Among several strategies used in breast cancer treatment, nanotechnology-based targeted therapy is currently being investigated, as it depicts advanced technological features able of preventing drugs' side effects on normal cells while effectively acting on tumor cells. In this context, carbohydrate polymer-based nanocomposites have gained particular interest among the biomedical community for breast cancer therapy applications due to their advantage features, including abundance in nature, biocompatibility, straightforward fabrication methods, and good physicochemical properties. In this review, the physicochemical properties and biological activities of carbohydrate polymers and their derivate nanocomposites were discussed. Then, various methods for the fabrication of carbohydrate polymer-based nanocomposites as well as their application in breast cancer therapy and future perspectives were discussed.}, } @article {pmid36637351, year = {2023}, author = {Zhi, R and Wu, K and Zhang, J and Liu, H and Niu, C and Li, S and Fu, L}, title = {PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.}, journal = {Cancer science}, volume = {114}, number = {5}, pages = {1912-1928}, pmid = {36637351}, issn = {1349-7006}, support = {31870860//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; 82173344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; Histones ; *Carcinoma, Papillary/metabolism ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.}, } @article {pmid36636972, year = {2022}, author = {Mareev, VY and Orlova, YA and Plisuk, AG and Pavlikova, EP and Akopyan, ZA and Matskeplishvili, ST and Malahov, PS and Krasnova, TN and Seredenina, EM and Potapenko, AV and Agapov, МA and Asratyan, DA and Dyachuk, LI and Samokhodskaya, LM and Mershina, EM and Sinitsyn, VE and Mareev, YV and Shatokhina, EA and Begrambekova, YL and Kamalov, AA}, title = {Proactive anti-inflammatory therapy in the advanced stages of a new coronavirus infection. Main results of the inpatient phase of the COLORIT study (Colchicin vs. Ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with novel coronavirus infection COVID-19).}, journal = {Kardiologiia}, volume = {62}, number = {12}, pages = {11-22}, doi = {10.18087/cardio.2022.12.n2316}, pmid = {36636972}, issn = {0022-9040}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Inpatients ; Prospective Studies ; RNA, Viral ; Inflammation ; Colchicine ; Anti-Inflammatory Agents ; Treatment Outcome ; Cytokines ; }, abstract = {Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.}, } @article {pmid36633721, year = {2023}, author = {Han, S and Lee, SB and Gong, G and Lee, J and Chae, SY and Oh, JS and Moon, DH}, title = {Prognostic significance of pretreatment [18]F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with T2N1 hormone receptor-positive, ERBB2-negative breast cancer who underwent adjuvant chemotherapy.}, journal = {Breast cancer research and treatment}, volume = {198}, number = {2}, pages = {207-215}, pmid = {36633721}, issn = {1573-7217}, support = {HI18C2383//Ministry of Health and Welfare/ ; }, mesh = {Humans ; Female ; Positron Emission Tomography Computed Tomography/methods ; *Breast Neoplasms/diagnostic imaging/drug therapy ; Fluorodeoxyglucose F18 ; Prognosis ; *Triple Negative Breast Neoplasms ; Cohort Studies ; Positron-Emission Tomography/methods ; Chemotherapy, Adjuvant ; Radiopharmaceuticals ; Retrospective Studies ; Receptor, ErbB-2 ; }, abstract = {PURPOSE: To determine whether tumor uptake of [18]F-fluorodeoxyglucose ([18]F-FDG) is associated with invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive ERBB2-negative early-stage breast cancer treated with adjuvant chemotherapy.

METHODS: This is a single-center cohort study of women with breast cancer who underwent surgery between 2008 and 2015 at Asan Medical Center, Seoul, Korea. Patients were enrolled if they were diagnosed with HR-positive ERBB2-negative breast cancer with histology of invasive ductal carcinoma, had an American Joint Committee on Cancer pathologic tumor stage of T2N1 with 1-3 positive axillary nodes, underwent preoperative [18]F-FDG positron emission tomography/computed tomography (PET/CT), and underwent breast cancer surgery followed by anthracycline- or taxane-based adjuvant chemotherapy. The primary outcome measure was IDFS. The maximum standardized uptake value (SUVmax) was dichotomized using a predefined cut-off of 4.14.

RESULTS: A total of 129 patients were included. The median follow-up period for IDFS in those without recurrence was 82 months (interquartile range, 65-106). Multivariable Cox analysis showed that SUVmax was independently associated with IDFS [adjusted hazard ratio 2.49; 95% confidence interval (CI), 1.06-5.84]. Ten-year IDFS estimates via the Kaplan-Meier method were 0.60 (95% CI, 0.42-0.74) and 0.82 (95% CI, 0.65-0.91) for high and low SUVmax groups, respectively. The overall association between SUVmax and IDFS appeared to be consistent across subgroups divided according to age, progesterone receptor status, histologic grade, or presence of lymphovascular invasion.

CONCLUSION: High SUVmax on preoperative [18]F-FDG PET/CT was independently associated with reduced long-term IDFS in T2N1 HR-positive ERBB2-negative breast cancer patients who underwent adjuvant chemotherapy.}, } @article {pmid36633438, year = {2023}, author = {Ganbold, E and Kim, ES and Li, Y and Yin, F and Sharma, PK and Jeon, JB and Oh, JM and Lee, DN and Kim, NY}, title = {Highly Sensitive Interdigitated Capacitive Humidity Sensors Based on Sponge-Like Nanoporous PVDF/LiCl Composite for Real-Time Monitoring.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {3}, pages = {4559-4568}, doi = {10.1021/acsami.2c20499}, pmid = {36633438}, issn = {1944-8252}, abstract = {In this study, a sponge-like poly(vinylidene fluoride) (PVDF)/lithium chloride (LiCl) nanocomposite-entrenched interdigitated capacitive (IDC) sensor was developed for real-time humidity-sensing applications. Here, we demonstrated a sponge-like nanoporous structure ranging from 200 nm to 2 μm size holes, the PVDF/LiCl structure fabricated on an interdigitated capacitor (IDC) electrode functioning as a high-performance sensor because of the presence of ionized LiCl. The nanoporous PVDF/LiCl composite-based humidity sensor exhibited a high sensitivity of 12.6 nF/% relative humidity (RH), a linearity of 0.990, and a low hysteresis of 2.6% in the range of 25-95% RH. The composite film exhibited a response time of 17.7 s, a recovery time of 21 s, and an intensified increase of 8.02 nF/s (a decrease of 6.7 nF/s). The sensor designed demonstrates ultra-high sensing characteristics with 10 times higher sensitivity, i.e., 12.678.96 pF/%RH as compared to other polymer-based composite humidity sensors. Owing to the sensing performance and portability, the proposed nanoporous PVDF/LiCl composite-based IDC sensor is expected to be a promising platform for a wide range of humidity-sensing applications, including real-time breath monitoring and non-contact sensing.}, } @article {pmid36631536, year = {2023}, author = {Hogenhout, R and Remmers, S and van Leenders, GJLH and Roobol, MJ}, title = {The transition from transrectal to transperineal prostate biopsy without antibiotic prophylaxis: Cancer detection rates and complication rates.}, journal = {Prostate cancer and prostatic diseases}, volume = {26}, number = {3}, pages = {581-587}, pmid = {36631536}, issn = {1476-5608}, mesh = {Male ; Humans ; *Prostate/pathology ; *Prostatic Neoplasms/diagnosis/pathology ; Anti-Bacterial Agents/therapeutic use ; Image-Guided Biopsy/adverse effects ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Currently, transperineal prostate biopsy (TPB) is preferred over transrectal biopsy (TRB) because of less infectious complications and improved clinically significant prostate cancer (csPCa) detection. However, literature on omitting antibiotic prophylaxis (AP) is limited. Furthermore, previous studies did not include invasive cribriform growth/intraductal carcinoma (CR/IDC) in the definition of csPCa. Therefore, we compared the infectious complication rates between TPB without AP and TRB with AP, and we compared the csPCa detection rates between TPB and TRB including CR/IDC in the definition of csPCa.

METHODS: We included 729 men who were referred to Erasmus MC Cancer Institute between 2013-2019 for MRI/TRUS fusion-guided prostate biopsy. Up to 2019, TRB was performed with AP, thereafter TPB was performed without AP. Data on complications were collected prospectively. We compared csPCa detection rates between the biopsy routes using multivariable logistic regressions for men without previous PCa diagnosis and mixed logistic regression for men on active surveillance. To compare the csPCa detection rates in anterior and apical lesions, and the complications rates between the biopsy routes, we used the chi-square test.

RESULTS: Overall, we found no difference in csPCa detection between TPB and TRB (odds ratio 1.0, 95%-confidence interval (CI) 0.62-1.76, p = 0.9; for men on active surveillance: odds ratio 1.05, 95%-CI 0.58-1.88, p = 0.9). This was confirmed in anterior and apical lesions although absolute numbers were low. TPB reduced infectious complications with fever compared to TRB (1.1% vs 5.1%, difference = 4.0%, 95%-CI 1.0-7.9, p = 0.010).

CONCLUSIONS: TPB has no different csPCa detection rate from TRB taking CR/IDC into account. TPB is, however, preferable because of less infectious complications, even if AP is omitted.}, } @article {pmid36626910, year = {2023}, author = {Quagliarotti, C and Cortesi, M and Coloretti, V and Fantozzi, S and Gatta, G and Bonifazi, M and Zamparo, P and Piacentini, MF}, title = {The Effects of a Wetsuit on Biomechanical, Physiological, and Perceptual Variables in Experienced Triathletes.}, journal = {International journal of sports physiology and performance}, volume = {18}, number = {2}, pages = {171-179}, doi = {10.1123/ijspp.2022-0029}, pmid = {36626910}, issn = {1555-0273}, mesh = {Humans ; Biomechanical Phenomena ; *Respiration ; *Swimming/physiology ; Arm/physiology ; }, abstract = {PURPOSE: Wetsuits have been shown to change swim biomechanics and, thus, increase performance, but not all athletes are comfortable with their use because of possible modifications in motor coordination. The aim of this study was to evaluate the effects of wetsuit use on biomechanical, physiological, and perceptual variables.

METHODS: Eleven national- and international-level triathletes, familiar with wetsuit use, performed 7 × 200-m front crawl at constant preset speed twice, with and without a full wetsuit. The trunk incline (TI) and index of coordination (IdC) were measured stroke by stroke using video analysis. Stroke, breaths, and kick count, and timing (as breathing/kick action per arm-stroke cycle); stroke length (SL); and underwater length were analyzed using inertial-measurement-unit sensors. Heart rate (HR), rating of perceived exertion (RPE), and swimming comfort were monitored during the task.

RESULTS: A lower TI; IdC; number of strokes, kicks, and breaths; HR; and RPE for each 200 m were found in wetsuit compared with swimsuit condition. Higher values of SL and underwater length were found in wetsuit, whereas no differences were found in swimming comfort and timing of kicks and breaths. An increase for swimsuit condition in number of strokes and breaths, HR, and RPE was found during the task compared with the first 200 m.

CONCLUSION: Wetsuit use reduces TI and, thus, drag; increases propelling proficiency; and shows lower fatigability, without modifying motor coordination, compared with swimsuit use at the same speed. The use of a wetsuit during training sessions is recommended to increase comfort and the positive effects on performance.}, } @article {pmid36624021, year = {2023}, author = {Zhang, J and Liu, Y and Fan, H and Wang, W and Shao, W and Cao, G and Shi, X}, title = {Prediction of Clinical Molecular Typing of Breast Invasive Ductal Carcinoma Using [18]F-FDG PET/CT Dual-Phase Imaging.}, journal = {Academic radiology}, volume = {30 Suppl 2}, number = {}, pages = {S82-S92}, doi = {10.1016/j.acra.2022.12.036}, pmid = {36624021}, issn = {1878-4046}, mesh = {Female ; Humans ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Ki-67 Antigen ; *Triple Negative Breast Neoplasms ; Positron-Emission Tomography/methods ; *Carcinoma, Ductal ; *Breast Neoplasms/diagnostic imaging ; Radiopharmaceuticals ; *Carcinoma, Ductal, Breast/diagnostic imaging ; }, abstract = {RATIONALE AND OBJECTIVES: To investigate the diagnostic value of Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography ([18]F-FDG PET/CT) dual-phase imaging for the different molecular subtypes of invasive ductal carcinoma of the breast.

MATERIALS AND METHODS: Clinical imaging data of 164 women with invasive ductal carcinoma of the breast confirmed by pathology who underwent [18]F-FDG PET/CT dual-phase imaging were retrospectively analyzed. The maximum standard uptake values (SUVmax) of the early and delayed phases of the lesion were measured and recorded as SUVmax1 and SUVmax2, respectively, and the retention index (RI) was calculated. We analyzed the change rule of SUVmax1, SUVmax2, and RI for the different molecular subtypes and molecular marker expression groups. The diagnostic threshold of different molecular marker expression status was determined using receiver operating characteristic curve analysis.

RESULTS: SUVmax1 and SUVmax2 were highest in the TNBC group and lowest in the luminal A group (p<0.001). TNBC and HER2 overexpression groups had higher RI than the luminal A and B groups (p<0.001), with no significant difference between the TNBC and HER2 overexpression groups or between the luminal A and B groups (p=0.640 and 0.345, respectively). The ER- and PR-negative groups had significantly higher SUVmax1, SUVmax2, and RI than the PR-positive group (p<0.001). The HER2-positive group had higher SUVmax1 and SUVmax2 than the negative group (p<0.001). The Ki67 overexpression group had higher SUVmax1 and SUVmax2 levels than the low expression group (p<0.001). There was no significant difference in RI between HER2-positive and negative groups or between Ki67 high and low expression groups (p=0.904 and 0.216, respectively). For ER-negative and positive expression status, the maximum area under the curve (AUC) of SUVmax2 was 0.852, diagnostic threshold was 10.87, sensitivity was 79.6%, and specificity was 74.5%. For PR-negative and positive expression status, the AUC of SUVmax2 was 0.858, diagnostic threshold was 10.45, sensitivity was 83.1%, and specificity was 75.3%. For HER2-negative and positive expression status, the AUC of SUVmax1 was 0.714, diagnostic threshold was 9.28, sensitivity was 79.6%, and specificity was 60.9%. For Ki67 high- and low expression status, the AUC of SUVmax2 was 0.915 at maximum, diagnostic threshold was 10.21, sensitivity was 83.4%, and specificity was 93.9%.

CONCLUSION: [18]F-FDG PET/CT dual-phase imaging facilitates the prediction of the expression of molecular markers and subtypes of invasive ductal carcinoma of the breast and the development of more tailored treatment plans for patients with this disease.}, } @article {pmid36617494, year = {2023}, author = {Matta, L and Blaas, L and de Faria, CC}, title = {From honeymoon to dysfunction: brown fat remodelling in obesity.}, journal = {The Journal of physiology}, volume = {601}, number = {4}, pages = {711-713}, doi = {10.1113/JP284187}, pmid = {36617494}, issn = {1469-7793}, mesh = {Humans ; Animals ; Mice ; *Adipose Tissue, Brown ; *Obesity ; Diet, High-Fat ; Mice, Inbred C57BL ; }, } @article {pmid36616805, year = {2022}, author = {Ahmad, S and Khosravi, R and Iyer, AK and Mirzavand, R}, title = {Wireless Capacitive Liquid-Level Detection Sensor Based on Zero-Power RFID-Sensing Architecture.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {1}, pages = {}, pmid = {36616805}, issn = {1424-8220}, support = {NA//Natural Sciences and Engineering Research Council/ ; NA//Future Energy Systems/ ; }, abstract = {In this paper, a new method for the wireless detection of liquid level is proposed by integrating a capacitive IDC-sensing element with a passive three-port RFID-sensing architecture. The sensing element transduces changes in the liquid level to corresponding fringe-capacitance variations, which alters the phase of the RFID backscattered signal. Variation in capacitance also changes the resonance magnitude of the sensing element, which is associated with a high phase transition. This change in the reactive phase is used as a sensing parameter by the RFID architecture for liquid-level detection. Practical measurements were conducted in a real-world scenario by placing the sensor at a distance of approximately 2 m (with a maximum range of about 7 m) from the RFID reader. The results show that the sensor node offers a high sensitivity of 2.15°/mm to the liquid-level variation. Additionally, the sensor can be used within or outside the container for the accurate measurement of conductive- or non-conductive-type liquids due to the use of polyethylene coating on the sensitive element. The proposed sensor increases the reliability of the current level sensors by eliminating the internal power source as well as complex signal-processing circuits, and it offers real-time response, linearity, high sensitivity, and excellent repeatability, which are suitable for widespread deployment of sensor node applications.}, } @article {pmid36613131, year = {2023}, author = {Norouzi, N and Angel, JL}, title = {Intergenerational Day Centers: A New Wave in Adult and Child Day Care.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36613131}, issn = {1660-4601}, mesh = {Child ; Humans ; Aged ; *Child Care ; *Child Day Care Centers ; }, abstract = {Intergenerational Day Centers (IDCs) are an innovation that addresses two important societal challenges, the continuing need for childcare and the emerging demand for older-adult supportive services that help them remain independent in their homes. These facilities provide care, and specialized resources and activities for both older adults and children in one location. While the importance and benefits of these programs have been proven, there is scant information in the literature and best-practice guidelines on the planning and development of these programs. This qualitative study focuses on the research, planning, and building development for new IDCs in metropolitan areas. It is based on a case example of the process of establishing an IDC in the City of Austin, which was an element of the Age-Friendly Austin Plan. It examines the applicable literature and the extensive involvement of experts in architecture, community planning, and public health policy as well as data collected from community engagement workshops to facilitate the IDC's creation and operation. This study offers a developmental strategy method that can be adopted and utilized by other cities, developers, and designers who are interested in building IDCs.}, } @article {pmid36611608, year = {2023}, author = {Kim, KY and Jang, CW and Chung, SY and Kim, M and Cho, SR and Cho, HE}, title = {Usefulness of YouTube in Sharing Information about New Gene Therapy for Spinal Muscular Atrophy: A Content Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {36611608}, issn = {2227-9032}, abstract = {This study aimed to objectively assess YouTube videos' quality, reliability, and information delivery capability regarding novel spinal muscular atrophy treatments. Using the keywords "nusinersen", "spinraza", "ridisplam", "evrysdi", "onasemnogene abeparvovec", and "zolgensma", we were able to retrieve and screen 360 videos before settling on a final sample of 99 on 25 September 2022. Then, two independent raters used the mDISCERN and GQS instruments to evaluate the videos' reliability and quality and the Information Delivery Capability (IDC) score to assess the videos' accuracy and patient-friendliness. The quality, reliability, and information delivery capability of the videos about the new treatment for SMA were quite heterogeneous, with an average mDISCERN, GQS, and IDC score of 3.172 ± 0.899, 2.980 ± 1.025, and 4.141 ± 1.747, respectively. In-depth analysis showed that healthcare expert videos that explained contents while showing infographic supplements had good quality, reliability, and information delivery capability. As YouTube is already a dominant media platform, the public may obtain new information about novel therapeutics for SMA through YouTube. It is necessary to consider how SMA patients and caregivers can choose trusted sources with reliable information on YouTube, and our results can provide clues. Additionally, experts should strive to provide more accurate, reliable, and patient-oriented videos.}, } @article {pmid36608855, year = {2023}, author = {Aune, T and Hamiel, D and Wolmer, L}, title = {Does emotion regulation mediate the effect of stressful life events on depressive symptoms in adolescents?.}, journal = {Journal of affective disorders}, volume = {325}, number = {}, pages = {354-359}, doi = {10.1016/j.jad.2022.12.158}, pmid = {36608855}, issn = {1573-2517}, mesh = {Humans ; Female ; Adolescent ; Male ; *Depression/psychology ; *Emotional Regulation ; Life Change Events ; Cross-Sectional Studies ; Emotions/physiology ; }, abstract = {INTRODUCTION: Adolescents' exposure to stressful life events (SLEs) is highly prevalent and increases their risk of developing depression considerably. A small number of studies have addressed the extent to which resilience factors, such as the ability to emotionally regulate, mediate the relationship between SLEs and depression. This study examined whether emotion regulation mediates and significantly attenuates the direct path between SLEs and depressive symptoms in a nonclinical sample of adolescents.

METHOD: A sample of 235 first- and second-year high-school students completed the Depression Anxiety Stress Scale, the Risk Factor Questionnaire, and the Difficulties in Emotion Regulation Scale. Mean age was 16.9 (SD = 1.8) years, and 65 % (n = 152) of the participants were female. To assess for mediation, a regression-based path analysis approach was used.

RESULTS: SLEs were significantly (t = 5.13, p < 0.001) associated with depressive symptoms, explaining 59.1 % of the total variance. Controlling for the mediation variable (emotion regulation), we found a reduced but statistically significant direct effect (t = 2.87, p = 0.005) between SLEs and depressive symptoms. A statistically significant indirect effect explaining 64.6 % of the total effect demonstrated partial mediation from stressful life events to depressive symptoms via emotion regulation.

LIMITATIONS: Our analyses are based on correlational and cross-sectional data and thus exclude statistical examination of temporal causal relationships, and assessments of whether reported affects are stable over time.

CONCLUSIONS: Our results indicate that interventions that can modify the ability to regulate emotions may help reduce depressive symptoms in at-risk adolescents.}, } @article {pmid36607851, year = {2023}, author = {Hadano, Y and Suyama, A and Hijikata, T and Miura, A and Fujii, S and Suzuki, Y and Tomoda, Y and Awaya, Y}, title = {The importance of infectious disease specialists consulting on a weekly basis in a Japanese tertiary care hospital: A retrospective observational study.}, journal = {Medicine}, volume = {102}, number = {1}, pages = {e32628}, pmid = {36607851}, issn = {1536-5964}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; Cefepime ; Meropenem ; Tertiary Care Centers ; Retrospective Studies ; East Asian People ; Referral and Consultation ; *Communicable Diseases/diagnosis ; Piperacillin, Tazobactam Drug Combination ; }, abstract = {Limited data are available regarding part-time infectious disease consultations (IDCs) and their importance in tertiary care teaching hospitals in Japan. This is a retrospective review of IDCs from June 2016 to March 2021 and describes IDC services provided by part-time infectious disease specialists once a week for 4 hours, and their impact on the quality of medical care, including antimicrobial stewardship. Data, such as the requesting department, requesting reasons, and final diagnoses, were analyzed. In April 2018, part-time infectious disease specialists launched consultation services and attended an antimicrobial stewardship team conference. Meropenem, tazobactam/piperacillin, and cefepime monthly days of therapy (DOT) were calculated to assess the effect of each intervention; a pre-post analysis was conducted using the Kruskal-Wallis test. Additional quality improvement (QI) projects related to infectious diseases were implemented. There were 237 IDCs during the study period. Consultations were mostly requested by the General Internal Medicine, Emergency Medicine, and Cardiology departments. The most common diagnoses were bone/joint, respiratory, and genitourinary infections. Infectious disease services, even on a part-time basis, achieve good outcomes in patient management, antimicrobial stewardship, and QI projects. DOT/1000 patient-days were reduced for meropenem and cefepime, while it increased for tazobactam/piperacillin. The DOT/1000 patient-days for the 3-antipseudomonal agents significantly decreased during this period. After implementing the QI tetanus vaccination project in the Emergency Room, the number of tetanus toxoid vaccinations per month increased.}, } @article {pmid36604587, year = {2023}, author = {Nasrazadani, A and Li, Y and Fang, Y and Shah, O and Atkinson, JM and Lee, JS and McAuliffe, PF and Bhargava, R and Tseng, G and Lee, AV and Lucas, PC and Oesterreich, S and Wolmark, N}, title = {Mixed invasive ductal lobular carcinoma is clinically and pathologically more similar to invasive lobular than ductal carcinoma.}, journal = {British journal of cancer}, volume = {128}, number = {6}, pages = {1030-1039}, pmid = {36604587}, issn = {1532-1827}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/drug therapy ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; }, abstract = {BACKGROUND: Mixed invasive ductal lobular carcinoma (mDLC) remains a poorly understood subtype of breast cancer composed of coexisting ductal and lobular components.

METHODS: We sought to describe clinicopathologic characteristics and determine whether mDLC is clinically more similar to invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC), using data from patients seen at the University of Pittsburgh Medical Center.

RESULTS: We observed a higher concordance in clinicopathologic characteristics between mDLC and ILC, compared to IDC. There is a trend for higher rates of successful breast-conserving surgery after neoadjuvant chemotherapy in patients with mDLC compared to patients with ILC, in which it is known to be lower than in those with IDC. Metastatic patterns of mDLC demonstrate a propensity to develop in sites characteristic of both IDC and ILC. A meta-analysis evaluating mDLC showed shared features with both ILC and IDC with significantly more ER-positive and fewer high grades in mDLC compared to IDC, although mDLCs were significantly smaller and included fewer late-stage tumours compared to ILC.

CONCLUSIONS: These findings support clinicopathologic characteristics of mDLC driven by individual ductal vs lobular components and given the dominance of lobular pathology, mDLC features are often more similar to ILC than IDC. This study exemplifies the complexity of mixed disease.}, } @article {pmid36602069, year = {2022}, author = {Serrano-Quintero, A and Sequeda-Juárez, A and Pérez-Hernández, CA and Sosa-Delgado, SM and Mendez-Tenorio, A and Ramón-Gallegos, E}, title = {Immunogenic analysis of epitope-based vaccine candidate induced by photodynamic therapy in MDA-MB-231 triple-negative breast cancer cells.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {40}, number = {}, pages = {103174}, doi = {10.1016/j.pdpdt.2022.103174}, pmid = {36602069}, issn = {1873-1597}, mesh = {Humans ; Female ; Photosensitizing Agents ; *Photochemotherapy/methods ; Calreticulin/metabolism/therapeutic use ; Epitopes/therapeutic use ; *Triple Negative Breast Neoplasms/drug therapy ; *Breast Neoplasms ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Vaccines/therapeutic use ; Cytokines/metabolism ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Photodynamic therapy (PDT) is used to treat tumors through selective cytotoxic effects. PDT induces damage-associated molecular patterns (DAMPs) expression, which can cause an immunogenic death cell (IDC). In this study we identified potential immunogenic epitopes generated by PDT on triple-negative breast cancer cell line (MDA-MB-231).

METHODS: MDA-MB-231 cells were exposed to PDT using ALA (160 µg/mL)/630 nm at 8 J/cm[2]. Membrane proteins were extracted and separated by 2D PAGE. Proteins overexpressed were identified by LC-MS/MS and analyzed in silico through a peptide-HLA docking in order to identify the epitopes with more immunogenicity and antigenicity properties, as well as lower allergenicity and toxicity activity. The selected peptides were evaluated in response to macrophage activation and cytokine release by flow cytometry.

RESULTS: Differential proteins were overexpressed in the cells treated with PDT. A group of 16 peptides were identified from them, established in a rigorous selection by measuring antigenicity, immunogenicity, allergenicity, and toxicity in silico. The final selection was based on molecular dynamics, where 2 peptides showed the highest stability regarding to the RMSD value. These peptides were obtained from the proteins calreticulin and HSP90. The cytokine analysis evidenced macrophage activation by the releasing of TNF.

CONCLUSION: Two peptides were identified from calreticulin and HSP90; proteins induced by PDT in MDA-MB-231 cells. Both epitopes showed immunogenic potential as a peptide-based vaccine for triple-negative breast cancer.}, } @article {pmid36600790, year = {2022}, author = {Kimchy, AV and Umoren, MD and Rosenberg, JJ and Ilagan, C and Nithagon, P and Shafa, S and Jennings, JJ}, title = {Breast Cancer Metastasis to the Gastrointestinal Tract With Unusual Endoscopic and Histologic Presentations.}, journal = {ACG case reports journal}, volume = {9}, number = {12}, pages = {e00938}, pmid = {36600790}, issn = {2326-3253}, abstract = {The gastrointestinal (GI) tract is an infrequent site of breast cancer metastasis, but it often poses a diagnostic challenge when it occurs. The symptoms of GI metastases are often nonspecific, and the endoscopic manifestations are variable, requiring tissue biopsies for histologic examination. We report 2 cases of breast cancer metastasizing to the GI tract: a case of human epidermal growth factor receptor 2-positive invasive ductal carcinoma that metastasized to the stomach, a rare location for this histologic subtype, and another case of invasive lobular cell carcinoma that metastasized to the colon with unusual findings of mucosal pallor and edema on colonoscopy.}, } @article {pmid36600314, year = {2023}, author = {Park, HL and Lee, SW and Hong, JH and Lee, J and Lee, A and Kwon, SJ and Park, SY and Yoo, IR}, title = {Prognostic impact of [18]F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {23}, number = {1}, pages = {2}, pmid = {36600314}, issn = {1470-7330}, mesh = {Humans ; Female ; Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology ; Fluorodeoxyglucose F18/metabolism ; Prognosis ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/therapy/metabolism ; Radiopharmaceuticals ; }, abstract = {BACKGROUND: The aim of this study is to investigate the impact of [18]F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery.

METHODS: The clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model.

RESULTS: There were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29-5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS.

CONCLUSION: Metabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.}, } @article {pmid36599340, year = {2022}, author = {Kim, MH and Suh, J and Kong, HJ and Oh, SJ}, title = {Maximum Voided Volume Is a Better Clinical Parameter for Bladder Capacity Than Maximum Cystometric Capacity in Patients With Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: A Prospective Cohort Study.}, journal = {International neurourology journal}, volume = {26}, number = {4}, pages = {317-324}, pmid = {36599340}, issn = {2093-4777}, support = {04-2019-0390//Seoul National University Hospital/ ; }, abstract = {PURPOSE: Bladder capacity is an important parameter in the diagnosis of lower urinary tract dysfunction. We aimed to determine whether the maximum bladder capacity (MCC) measured during a urodynamic study was affected by involuntary detrusor contraction (IDC) in patients with Lower Urinary Tract Symptoms (LUTS)/Benign Prostatic Hyperplasia (BPH).

METHODS: Between March 2020 and April 2021, we obtained maximum voided volume (MVV) from a 3-day frequency-volume chart, MCC during filling cystometry, and maximum anesthetic bladder capacity (MABC) during holmium laser enucleation of the prostate under spinal or general anesthesia in 139 men with LUTS/BPH aged >50 years. Patients were divided according to the presence of IDC during filling cystometry. We assumed that the MABC is close to the true value of the MCC, as it is measured under the condition of minimizing neural influence over the bladder.

RESULTS: There was no difference in demographic and clinical characteristics between the non-IDC (n=20) and IDC groups (n=119) (mean age, 71.5±7.4) (P>0.05). The non-IDC group had greater bladder volume to feel the first sensation, first desire, and strong desire than the IDC group (P<0.001). In all patients, MABC and MVV were correlated (r=0.41, P<0.001); however, there was no correlation between MCC and MABC (r=0.19, P=0.02). There was no significant difference in MABC between the non-IDC and IDC groups (P=0.19), but MVV and MCC were significantly greater in the non-IDC group (P<0.001). There was no significant difference between MABC and MVV (MABC-MVV, P=0.54; MVV/MABC, P=0.07), but there was a significant difference between MABC and MCC between the non-IDC and IDC groups (MABC-MCC, P<0.001; MCC/MABC, P<0.001).

CONCLUSION: Maximum bladder capacity from a urodynamic study does not represent true bladder capacity because of involuntary contractions.}, } @article {pmid36596982, year = {2023}, author = {Watson, JF and Radic, R and Frost, R and Paton, S and Kessell, MA and Dessauvagie, BF and Taylor, DB}, title = {Vacuum-assisted excision biopsy for definitive diagnosis of breast lesions of uncertain malignant potential (B3 lesions) on core biopsy - A single centre Western Australian experience.}, journal = {Journal of medical imaging and radiation oncology}, volume = {67}, number = {4}, pages = {365-376}, doi = {10.1111/1754-9485.13502}, pmid = {36596982}, issn = {1754-9485}, mesh = {Female ; Humans ; *Mammography ; Australia ; Breast/diagnostic imaging/pathology ; Biopsy, Needle ; Biopsy ; Image-Guided Biopsy ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: In Australia, the usual approach to breast lesions where core biopsy returns an uncertain result ("B3" breast lesion) is to perform surgical diagnostic open biopsy (DOB). This is associated with patient time off work, costs of hospital admission, risks of general anaesthesia and surgical complications. The majority of B3 lesions return benign results following surgery. Vacuum assisted excision biopsy (VAEB) is a less invasive, lower cost alternative, and is standard of care for selected B3 lesions in the United Kingdom. Similar use of VAEB in Australia, could save many women unnecessary surgery. The aim of this study was to document our experience during the introduction of VAEB as an alternative to DOB for diagnosis of selected B3 lesions.

METHODS: The multidisciplinary team developed an agreed VAEB pathway for selected B3 lesions. Technically accessible papillary lesions, mucocele-like lesions and radial scars without atypia measuring ≤ 15mm were selected.

RESULTS: Over a 7 month period, 18 women with 20 B3 lesions were offered VAEB. 16 women (18 lesions) chose VAEB over DOB. Papillomas were the commonest lesion type. All lesions were successfully sampled: 17/18 were benign. One lesion (6%) was upgraded to malignancy (ductal carcinoma in situ on VAEB, invasive ductal carcinoma at surgery). No major complications occurred. Patient satisfaction was high: 15/16 respondents would again choose VAEB over surgery.

CONCLUSION: VAEB is a patient-preferred, safe, well-tolerated, lower-cost alternative to DOB for definitive diagnosis of selected B3 breast lesions.}, } @article {pmid36591521, year = {2022}, author = {Yang, Y and Zhang, W and Wan, L and Tang, Z and Zhang, Q and Bai, Y and Zhang, D}, title = {Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1074478}, pmid = {36591521}, issn = {2234-943X}, abstract = {INTRODUCTION: Intraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes.

OBJECTIVE: To establish an effective predictive model for predicting IDC-P.

METHODS: Data for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People's Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People's Hospital and 430 patients from Jiaxing Second People's Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model.

RESULTS: Univariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P.

CONCLUSION: We developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.}, } @article {pmid36590775, year = {2022}, author = {Abur, PP and Yusufu, LM and Odigie, VI and Emeka, NS}, title = {Metachronous Contralateral Breast Cancer in Ahmadu Bello University Teaching Hospital, Zaria, Northwestern Nigeria.}, journal = {Journal of the West African College of Surgeons}, volume = {12}, number = {4}, pages = {52-55}, pmid = {36590775}, issn = {2276-6944}, abstract = {BACKGROUND: Breast cancer is the most frequent cancer of women. Metachronous contralateral breast cancer (MCBC) is a cancer in the contralateral breast after 6 months of the initial diagnosis of the first breast cancer. It is an important public health issue because of an increased incidence of a primary breast cancer and improved survival. There is a paucity of data in the Northwestern region of the country. The study was to document the incidence, the method of detection, clinicopathological features, and the treatment of MCBC in our hospital.

PATIENTS AND METHODS: It was a 7-year prospective study from January 2011 to December 2017. Patients who had treatment for nonmetastatic breast cancer, American Joint Committee on Cancer (AJCC) Stages 1-111, were followed up. Those that developed MCBC were studied. Age, the method of detection, stage at presentation, pathological types, hormone receptor status, and treatment were documented. Data obtained were analysed using SPSS version 21.0. Results were presented as simple percentages and charts.

RESULTS: Of 1285 women with nonmetastatic breast cancer, 47 had MCBC (incidence of 3.7%); 30 (63.8%) were aged 21-50 years; 23 (48.9%) detected by self-breast examination; 13 (27.7%) by clinical breast examination; seven (14.9%) by mammography; and four (8.5%) by breast ultrasound scan. Fourteen (29.8%) were AJCC stage I; 23 (48.9%), stage II; seven (14.9%), stage III; and three (6.4%), stage IV. Thirty-nine (83%) were invasive ductal carcinoma; 22 (50.0%) were estrogen receptor/progesterone receptor (ER/PR) positive, human epidermal receptor (HER)-2 neu negative; nine were (20.5%) ER/PR and HER-2 neu positive; six (13.6%) were ER/PR negative, HER-2 neu positive, whereas seven (15.9%) were triple negative. Forty-three (91.5%) had modified radical mastectomy and 19 (40.4%) had cytotoxics.

CONCLUSION: With an average of six cases in a year, MCBC is common in our hospital. Majority (63.8%) were young. The commonest method of detection was by self-breast examination. Majority (78.3%) presented at an early stage. Most (91.5%) still had modified radical mastectomy.}, } @article {pmid36587134, year = {2023}, author = {Levy-Jurgenson, A and Tekpli, X and Kristensen, VN and Yakhini, Z}, title = {Analysis of Spatial Molecular Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2614}, number = {}, pages = {349-356}, pmid = {36587134}, issn = {1940-6029}, mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Phenotype ; Algorithms ; Microscopy/methods ; }, abstract = {Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.}, } @article {pmid36586492, year = {2023}, author = {Ward, MC and Recht, A and Vicini, F and Al-Hilli, Z and Asha, W and Chadha, M and Abraham, A and Thaker, N and Khan, AJ and Keisch, M and Shah, C}, title = {Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older.}, journal = {International journal of radiation oncology, biology, physics}, volume = {116}, number = {3}, pages = {617-626}, doi = {10.1016/j.ijrobp.2022.12.028}, pmid = {36586492}, issn = {1879-355X}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/radiotherapy/pathology ; Cost-Effectiveness Analysis ; Anastrozole ; Breast/pathology ; Aromatase Inhibitors ; Cost-Benefit Analysis ; Hormones ; }, abstract = {PURPOSE: The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination.

METHODS AND MATERIALS: We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective."

RESULTS: The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%.

CONCLUSIONS: U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.}, } @article {pmid36584059, year = {2022}, author = {Farouk, O and Ezzat, M and El-Badrawy, A and Fady, T and El-Kashef, W and Shams, N and Senbel, A}, title = {Charcoal Localization for Surgical Resection of Non-Palpable Suspicious Breast Lesions.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {117}, number = {6}, pages = {671-680}, doi = {10.21614/chirurgia.2802}, pmid = {36584059}, issn = {1221-9118}, mesh = {Humans ; Adult ; Female ; *Breast Neoplasms/diagnostic imaging/surgery ; Mammography/methods ; Charcoal ; Prospective Studies ; Mastectomy ; Treatment Outcome ; Mastectomy, Segmental ; }, abstract = {Background: Breast cancer is more frequently detected as radiographic non-palpable lesions with the increased utilization of national screening programs. Moreover, the sizes of tumors detected have decreased in recent years, increasing the need for accurate image-directed localization for surgical excision in a significant portion of cases. Although Wire guided localization has been the most commonly used method for many years, inherent problems remain and limit its practice. Radio-guided occult lesion localization (ROLL) is currently the standard method of localization, however, it is unavailable in most low resource communities. This encourages us to use charcoal localization which is a simple and cheap method of surgical localization of non-palpable suspicious breast lesions. Methods: This prospective study included 34 patients who presented with non-palpable suspicious breast lesions (BIRADS 4 or 5). All patients were injected 1-3 ml of sterilized 3% aqueous suspension of charcoal granules under the guidance of ultrasound at the superficial border of the suspicious lesion and the track between the lesion and the needle entry point in the skin which will occur at the future incision. This method was carried out in most patients one day before the operation, however, two patients underwent surgical excision after 6 days of localization without any interruption. Results: Thirty-four patients had 36 Lesions. The median age was 43 years. The mean diameter of lesions was 10.9 mm. Of 36 lesions; the BIRADS as follow10 (4a), 12 (4b), 8 (4c), and 6 (5). Postoperative investigations revealed 16 malignant lesions and 20 benign lesions. All 20 benign lesions were managed by wide local excision; All 14 BIRADS 4a lesions were proved to be benign. Sixteen malignant lesions were managed as the following; nine patients had breast-conserving surgery, five patients had modified radical mastectomy (three patients had past history of modified radical mastectomy, one patient had Multicentric IDC and one patient had infiltrated safety margins on conservation), and one patient had Nipple Sparing Mastectomy with immediate breast reconstruction by Latissimus Dorsi Flap. There was no reaction or infection reported in our study. Conclusion: Charcoal localization has many advantages and helps surgical localization.}, } @article {pmid36577560, year = {2023}, author = {Lerner, G and Tang, H and Singh, K and Golestani, R and St Claire, S and Humphrey, PA and Lannin, D and Janostiak, R and Harigopal, M}, title = {AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast, and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers.}, journal = {Clinical breast cancer}, volume = {23}, number = {2}, pages = {199-210}, doi = {10.1016/j.clbc.2022.11.012}, pmid = {36577560}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; *Triple Negative Breast Neoplasms/diagnosis ; Lymphatic Metastasis ; Biomarkers, Tumor/metabolism ; Neoplasm Recurrence, Local ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Racemases and Epimerases ; }, abstract = {BACKGROUND: Carcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist.

MATERIALS AND METHODS: α-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray.

RESULTS: AMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively).

CONCLUSION: AMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.}, } @article {pmid36577332, year = {2023}, author = {Lemel, R and Shalev, L and Nitsan, G and Ben-David, BM}, title = {Listen up! ADHD slows spoken-word processing in adverse listening conditions: Evidence from eye movements.}, journal = {Research in developmental disabilities}, volume = {133}, number = {}, pages = {104401}, doi = {10.1016/j.ridd.2022.104401}, pmid = {36577332}, issn = {1873-3379}, mesh = {Young Adult ; Humans ; *Speech Perception/physiology ; Eye Movements ; *Attention Deficit Disorder with Hyperactivity ; Quality of Life ; Word Processing ; Speech Disorders ; }, abstract = {BACKGROUND: Cognitive skills such as sustained attention, inhibition and working memory are essential for speech processing, yet are often impaired in people with ADHD. Offline measures have indicated difficulties in speech recognition on multi-talker babble (MTB) background for young adults with ADHD (yaADHD). However, to-date no study has directly tested online speech processing in adverse conditions for yaADHD.

AIMS: Gauging the effects of ADHD on segregating the spoken target-word from its sound-sharing competitor, in MTB and working-memory (WM) load.

METHODS AND PROCEDURES: Twenty-four yaADHD and 22 matched controls that differ in sustained attention (SA) but not in WM were asked to follow spoken instructions presented on MTB to touch a named object, while retaining one (low-load) or four (high-load) digit/s for later recall. Their eye fixations were tracked.

OUTCOMES AND RESULTS: In the high-load condition, speech processing was less accurate and slowed by 140ms for yaADHD. In the low-load condition, the processing advantage shifted from early perceptual to later cognitive stages. Fixation transitions (hesitations) were inflated for yaADHD.

CONCLUSIONS AND IMPLICATIONS: ADHD slows speech processing in adverse listening conditions and increases hesitation, as speech unfolds in time. These effects, detected only by online eyetracking, relate to attentional difficulties. We suggest online speech processing as a novel purview on ADHD. WHAT THIS PAPER ADDS?: We suggest speech processing in adverse listening conditions as a novel vantage point on ADHD. Successful speech recognition in noise is essential for performance across daily settings: academic, employment and social interactions. It involves several executive functions, such as inhibition and sustained attention. Impaired performance in these functions is characteristic of ADHD. However, to date there is only scant research on speech processing in ADHD. The current study is the first to investigate online speech processing as the word unfolds in time using eyetracking for young adults with ADHD (yaADHD). This method uncovered slower speech processing in multi-talker babble noise for yaADHD compared to matched controls. The performance of yaADHD indicated increased hesitation between the spoken word and sound-sharing alternatives (e.g., CANdle-CANdy). These delays and hesitations, on the single word level, could accumulate in continuous speech to significantly impair communication in ADHD, with severe implications on their quality of life and academic success. Interestingly, whereas yaADHD and controls were matched on WM standardized tests, WM load appears to affect speech processing for yaADHD more than for controls. This suggests that ADHD may lead to inefficient deployment of WM resources that may not be detected when WM is tested alone. Note that these intricate differences could not be detected using traditional offline accuracy measures, further supporting the use of eyetracking in speech tasks. Finally, communication is vital for active living and wellbeing. We suggest paying attention to speech processing in ADHD in treatment and when considering accessibility and inclusion.}, } @article {pmid36574856, year = {2023}, author = {Ying, Z and van Eenige, R and Beerepoot, R and Boon, MR and Kloosterhuis, NJ and van de Sluis, B and Bartelt, A and Rensen, PCN and Kooijman, S}, title = {Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.}, journal = {Pharmacological research}, volume = {187}, number = {}, pages = {106634}, doi = {10.1016/j.phrs.2022.106634}, pmid = {36574856}, issn = {1096-1186}, mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Brown ; Adrenergic Agonists/metabolism/pharmacology ; Apolipoproteins E/genetics/metabolism ; *Atherosclerosis/drug therapy/metabolism ; Cholesterol/metabolism ; Fatty Acids/metabolism ; Lipoproteins, LDL/metabolism ; Liver/metabolism ; Triglycerides ; Receptors, LDL/metabolism ; }, abstract = {Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.}, } @article {pmid36572997, year = {2023}, author = {Bendarkawi, Y and Cherif Chefchaouni, A and Lkhoyaali, S and Bechar, H and Boudina, Y and Abercha, Y and Belahcen, MJ and Rahali, Y}, title = {Tamoxifen induced hands deformities.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {5}, pages = {1246-1250}, doi = {10.1177/10781552221147507}, pmid = {36572997}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; *Tamoxifen/adverse effects ; Antineoplastic Agents, Hormonal/adverse effects ; *Breast Neoplasms/pathology ; Arthralgia/chemically induced ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer. In this article, we report a case of a patient who developed hand deformities following long-term administration of tamoxifen.

CASE REPORT: A 57-year-old woman, followed for invasive ductal carcinoma of the left breast under tamoxifen for 7 years, presenting joint pain with deformities in her fingers.

MANAGEMENT & OUTCOME: Following the appearance of the adverse effect, tamoxifen was stopped. A series of biologic and radiologic analysis were performed in order to explain the appearance of this event. A substitution treatment was discussed and a rheumatologist's opinion was requested.

DISCUSSION: Tamoxifen appears to be associated with the development of inflammatory osteoarthritis resembling rheumatoid arthritis. Possible mechanisms of such an effect are discussed.}, } @article {pmid36568215, year = {2022}, author = {Xu, ML and Zeng, SE and Li, F and Cui, XW and Liu, GF}, title = {Preoperative prediction of lymphovascular invasion in patients with T1 breast invasive ductal carcinoma based on radiomics nomogram using grayscale ultrasound.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1071677}, pmid = {36568215}, issn = {2234-943X}, abstract = {PURPOSE: The aim of this study was to develop a radiomics nomogram based on grayscale ultrasound (US) for preoperatively predicting Lymphovascular invasion (LVI) in patients with pathologically confirmed T1 (pT1) breast invasive ductal carcinoma (IDC).

METHODS: One hundred and ninety-two patients with pT1 IDC between September 2020 and August 2022 were analyzed retrospectively. Study population was randomly divided in a 7: 3 ratio into a training dataset of 134 patients (37 patients with LVI-positive) and a validation dataset of 58 patients (19 patients with LVI-positive). Clinical information and conventional US (CUS) features (called clinic_CUS features) were recorded and evaluated to predict LVI. In the training dataset, independent predictors of clinic_CUS features were obtained by univariate and multivariate logistic regression analyses and incorporated into a clinic_CUS prediction model. In addition, radiomics features were extracted from the grayscale US images, and the radiomics score (Radscore) was constructed after radiomics feature selection. Subsequent multivariate logistic regression analysis was also performed for Radscore and the independent predictors of clinic_CUS features, and a radiomics nomogram was developed. The performance of the nomogram model was evaluated via its discrimination, calibration, and clinical usefulness.

RESULTS: The US reported axillary lymph node metastasis (LNM) (US_LNM) status and tumor margin were determined as independent risk factors, which were combined for the construction of clinic_CUS prediction model for LVI in pT1 IDC. Moreover, tumor margin, US_LNM status and Radscore were independent predictors, incorporated as the radiomics nomogram model, which achieved a superior discrimination to the clinic_CUS model in the training dataset (AUC: 0.849 vs. 0.747; P < 0.001) and validation dataset (AUC: 0.854 vs. 0.713; P = 0.001). Calibration curve for the radiomic nomogram showed good concordance between predicted and actual probability. Furthermore, decision curve analysis (DCA) confirmed that the radiomics nomogram had higher clinical net benefit than the clinic_CUS model.

CONCLUSION: The US-based radiomics nomogram, incorporating tumor margin, US_LNM status and Radscore, showed a satisfactory preoperative prediction of LVI in pT1 IDC patients.}, } @article {pmid36563298, year = {2023}, author = {Braun, A and Reddy, S and Cheng, L and Gattuso, P and Yan, L}, title = {Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {42}, number = {4}, pages = {414-420}, doi = {10.1097/PGP.0000000000000920}, pmid = {36563298}, issn = {1538-7151}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; *Genital Neoplasms, Female/secondary ; *Krukenberg Tumor ; *Ovarian Neoplasms ; }, abstract = {Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.}, } @article {pmid36551567, year = {2022}, author = {Lin, SE and Chang, WW and Hsiao, PK and Hsieh, MC and Chen, WY and Fang, CL and Tsai, CC}, title = {Feasibility of Breast Cancer Metastasis Assessment of Ex Vivo Sentinel Lymph Nodes through a p-H&E Optical Coherence Microscopic Imaging System.}, journal = {Cancers}, volume = {14}, number = {24}, pages = {}, pmid = {36551567}, issn = {2072-6694}, support = {CMRPVVL0151//Chang Gung Medical Foundation/ ; }, abstract = {Frozen-sectioned hematoxylin-eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.}, } @article {pmid36548300, year = {2022}, author = {Shapiro-Kulnane, L and Selengut, M and Salz, HK}, title = {Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.}, journal = {PLoS genetics}, volume = {18}, number = {12}, pages = {e1010568}, pmid = {36548300}, issn = {1553-7404}, support = {R01 GM129478/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Male ; *Drosophila/metabolism ; Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; Germ Cells/metabolism ; Homeodomain Proteins/metabolism ; Zinc Fingers/genetics ; Female ; }, abstract = {H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.}, } @article {pmid36542569, year = {2022}, author = {Pratt, D and Sunassee, A}, title = {Syringomatous Adenoma of the Nipple with Associated Invasive Carcinoma: A Case Report.}, journal = {South Dakota medicine : the journal of the South Dakota State Medical Association}, volume = {75}, number = {7}, pages = {302-303}, pmid = {36542569}, issn = {0038-3317}, mesh = {Female ; Humans ; Adult ; Nipples/pathology ; *Syringoma/diagnosis/surgery/pathology ; *Adenoma/diagnosis/surgery ; *Adenocarcinoma/pathology ; *Sweat Gland Neoplasms/diagnosis/surgery/pathology ; *Breast Neoplasms/diagnosis/surgery/pathology ; }, abstract = {Syringomatous adenoma of the nipple is a rare benign infiltrative neoplasm that was first described in 1983. At the time of this writing, a literature search revealed no cases of syringomatous adenoma of the nipple in association with invasive carcinoma of the breast. We report a case of syringomatous adenoma of the nipple in a 40-year old female who also had bilateral invasive ductal carcinoma and ductal carcinoma in situ of the breasts. Syringomatous adenomas of the nipple have been postulated to originate from eccrine structures of the nipple due to their microscopic similarity to other tumors of eccrine origin, such as syringomatous carcinoma. However, their exact origin is uncertain. Despite their benign behavior, they usually demonstrate an infiltrative and expansile proliferation into adjacent nipple and breast tissue. They have been confused with tubular carcinoma and low-grade adenosquamous carcinoma of the breast, both clinically and histologically. Complete excision is the therapy of choice, and only incompletely excised lesions have shown recurrence. We present this case to raise awareness that syringomatous adenoma of the nipple may present in patients with a simultaneous invasive carcinoma of the breast.}, } @article {pmid36539444, year = {2022}, author = {Mouabbi, JA and Raghavendra, AS and Bassett, RL and Hassan, A and Tripathy, D and Layman, RM}, title = {Histology-based survival outcomes in hormone receptor-positive metastatic breast cancer treated with targeted therapies.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {131}, pmid = {36539444}, issn = {2374-4677}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {The addition of targeted therapies (TT) to endocrine therapy (ET) has improved the outcomes of patients with HR-positive, HER2-negative metastatic breast cancer (mBC). However, it is unknown whether patients with invasive lobular carcinoma (ILC) or mixed invasive ductal and lobular carcinoma (mixed) histologies experience the same magnitude of benefit from this therapy as those with invasive ductal carcinoma (IDC). We aim to determine whether patients with IDC, ILC, and mixed HR+/HER2- mBC derive similar benefit from the addition of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is), mammalian target of rapamycin inhibitor (mTORi), and phosphoinositide 3-kinase inhibitor (PI3Ki) to ET in HR+/HER2- mBC. We conducted an observational, population-based investigation using data from the MD Anderson prospectively collected database. We conducted a histology-based analysis of progression-free survival (PFS) and overall survival (OS) durations in 3784 patients with HR+/HER2- mBC who were treated with TT plus ET between January 1, 2010, and December 31, 2021. Out of the 3784 patients, 2975 were included in the final analysis. Of these, 2249 received CDK4/6is (81% IDC, 15% ILC, and 4% mixed), 1027 received everolimus (82% IDC, 14% ILC, and 4% mixed) and 49 received alpelisib (81% IDC and 19% ILC). The addition of targeted therapy to ET did not result in statistically significant differences in PFS or OS duration among patients with IDC, ILC, and mixed HR+/HER2- mBC. We concluded that for patients with HR+/HER2- mBC, the addition of TT to ET leads to a similar magnitude of benefit, irrespective of histology.}, } @article {pmid36539250, year = {2022}, author = {Sugihara, M and Nakao, M and Maejima, T and Kinoshita, R and Hayashi, S and Hirata, Y and Arakawa, S and Kuriyama, M and Muramatsu, H}, title = {[A Case of Second Primary Small Cell Lung Carcinoma after Radiotherapy for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {12}, pages = {1361-1364}, pmid = {36539250}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/radiotherapy/surgery/pathology ; *Small Cell Lung Carcinoma ; Mastectomy ; *Lung Neoplasms/surgery ; Lung/pathology ; }, abstract = {We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.}, } @article {pmid36527274, year = {2022}, author = {Ansari, N and Nisar, MI and Khalid, F and Mehmood, U and Usmani, AA and Shaheen, F and Hotwani, A and Begum, K and Barkat, A and Yoshida, S and Manu, AA and Sazawal, S and Baqui, AH and Bahl, R and Jehan, F}, title = {Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05055}, pmid = {36527274}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Child ; Female ; Humans ; Child, Preschool ; *COVID-19/epidemiology ; Seroepidemiologic Studies ; Prevalence ; Pakistan/epidemiology ; Prospective Studies ; Antibodies, Viral ; Risk Factors ; }, abstract = {BACKGROUND: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan.

METHODS: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys®. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis.

RESULTS: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI) = 42.6-47.9) and 82.3% (95% CI = 79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI = 16.1-20.7) and 57.4% (95% CI = 54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR) = 0.8, 95% CI = 0.7-0.9 and RR = 1.2, 95% CI = 1.1-1.4, respectively) and children (RR = 0.7, 95% CI = 0.5-1.0 and RR = 1.4, 95% CI = 1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR = 0.4, 95% CI = 0.3-0.7 and RR = 0.7, 95% CI = 0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR = 0.6, 95% CI = 0.4-0.9 and RR = 0.7, 95% CI = 0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR = 0.7, 95% CI = 0.6-0.9 and RR = 0.8, 95% CI = 0.7-1.0, respectively).

CONCLUSION: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.}, } @article {pmid36525512, year = {2023}, author = {Wagner, R and Heni, M and Kantartzis, K and Sandforth, A and Machann, J and Schick, F and Peter, A and Fritsche, L and Szendrödi, J and Pfeiffer, AFH and Schürmann, A and Blüher, M and Hauner, H and Seissler, J and Bornstein, S and Roden, M and Stefan, N and Birkenfeld, AL and White, MF and Häring, HU and Fritsche, A}, title = {Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention.}, journal = {Diabetes}, volume = {72}, number = {3}, pages = {362-366}, pmid = {36525512}, issn = {1939-327X}, mesh = {Humans ; *Prediabetic State/metabolism ; Insulin Secretion ; Blood Glucose/metabolism ; Liver/metabolism ; *Insulin Resistance ; Life Style ; Insulin/metabolism ; }, abstract = {The objective of this work was to investigate whether impaired insulin secretion can be restored by lifestyle intervention in specific subphenotypes of prediabetes. We assigned 1,045 participants from the Prediabetes Lifestyle Intervention Study (PLIS) to six recently established prediabetes clusters. Insulin secretion was assessed by a C-peptide-based index derived from oral glucose tolerance tests and modeled from three time points during a 1-year intervention. We also analyzed the change of glycemia, insulin sensitivity, and liver fat. All prediabetes high-risk clusters (cluster 3, 5, and 6) had improved glycemic traits during the lifestyle intervention, whereas insulin secretion only increased in clusters 3 and 5 (P < 0.001); however, high liver fat in cluster 5 was associated with a failure to improve insulin secretion (Pinteraction < 0.001). Thus, interventions to reduce liver fat have the potential to improve insulin secretion in a defined subgroup of prediabetes.}, } @article {pmid36519609, year = {2023}, author = {Yuce, E and Karakullukcu, S and Bulbul, H and Alandag, C and Saygin, I and Kavgaci, H}, title = {The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {1}, pages = {59-63}, doi = {10.4149/BLL_2023_009}, pmid = {36519609}, issn = {0006-9248}, mesh = {Female ; Humans ; Male ; Albumins/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; Hemoglobins ; Ki-67 Antigen ; Lymphocytes ; *Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Adult ; Middle Aged ; }, abstract = {INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses.

MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively.

RESULTS: The mean - age was 50.3±12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were ≤ T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was ≤ 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to ≤ 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged.

CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.}, } @article {pmid36510982, year = {2022}, author = {Azmat, H and Faridi, J and Habib, HM and Bugti, UJ and Sheikh, AK and Riaz, SK}, title = {Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {Supplement}, pages = {S313-S319}, doi = {10.4103/jcrt.JCRT_735_20}, pmid = {36510982}, issn = {1998-4138}, mesh = {Humans ; Female ; Receptor, ErbB-2/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; *Carcinoma/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Hormones ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.

OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.

MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.

RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.

CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.}, } @article {pmid36507575, year = {2023}, author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and van Bezouw, MJ and Rovenpor, D and Paladino, MP and Baumert, A and Bilewicz, M and Bilgen, A and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Petrović, N and Selvanathan, HP and Uluğ, ÖM and Wohl, MJ and Yeung, WLV and Young, K and Zein, RA}, title = {The distinct associations of ingroup attachment and glorification with responses to the coronavirus pandemic: Evidence from a multilevel investigation in 21 countries.}, journal = {The British journal of social psychology}, volume = {62}, number = {2}, pages = {992-1012}, doi = {10.1111/bjso.12614}, pmid = {36507575}, issn = {2044-8309}, mesh = {Humans ; *Pandemics/prevention & control ; *COVID-19 ; Communicable Disease Control ; Government ; Hygiene ; }, abstract = {While public health crises such as the coronavirus pandemic transcend national borders, practical efforts to combat them are often instantiated at the national level. Thus, national group identities may play key roles in shaping compliance with and support for preventative measures (e.g., hygiene and lockdowns). Using data from 25,159 participants across representative samples from 21 nations, we investigated how different modalities of ingroup identification (attachment and glorification) are linked with reactions to the coronavirus pandemic (compliance and support for lockdown restrictions). We also examined the extent to which the associations of attachment and glorification with responses to the coronavirus pandemic are mediated through trust in information about the coronavirus pandemic from scientific and government sources. Multilevel models suggested that attachment, but not glorification, was associated with increased trust in science and compliance with federal COVID-19 guidelines. However, while both attachment and glorification were associated with trust in government and support for lockdown restrictions, glorification was more strongly associated with trust in government information than attachment. These results suggest that both attachment and glorification can be useful for promoting public health, although glorification's role, while potentially stronger, is restricted to pathways through trust in government information.}, } @article {pmid36505983, year = {2022}, author = {Gupta, NK and Gaur, S and Pal, DK}, title = {Role of videourodynamics in the identification of causes of lower urinary tract symptoms and low uroflow in young men.}, journal = {Urology annals}, volume = {14}, number = {4}, pages = {332-335}, pmid = {36505983}, issn = {0974-7796}, abstract = {INTRODUCTION: The etiology of lower urinary tract symptoms (LUTS) is multifactorial with causes attributed either to the dysfunction of the bladder or its outlet. Although the etiologies are well studied in aged men, very limited research trials are available in young men with LUTS. Most of the time young men presenting with chronic irritative or obstructive symptoms are labeled with chronic prostatitis or prostatodynia and are treated empirically. In this study using videourodynamics, we prospectively investigated the etiologies of LUTS and low uroflow in young men.

MATERIALS AND METHODS: Fifty male patients, 18-50 years of age attending the urology outpatient department at a tertiary care center from January 2021 to December 2021 with symptoms suggestive of chronic LUTS and low uroflow (maximum urinary flow rate [Qmax] <15 ml/s at a voided volume >150 ml) were included in the study and underwent multichannel videourodynamic study (VUDS). Clinical characteristics and urodynamic results in different diagnostic groups were tabulated and analyzed. The P ≤ 0.05 was considered statistically significant.

RESULTS: Out of 50 enrolled patients, primary bladder neck obstruction was seen in 21 patients (42%), dysfunctional voiding in 14 (28%), impaired detrusor contractility (IDC) in 9 (18%), and benign prostatic obstruction (BPO) was noted in 6 patients (12%). The mean age and size of the prostate of patients with BPO were greater than those in the remaining groups and patients with IDC had lower Qmax and Pdet at Qmax than those in the remaining patients.

CONCLUSION: Chronic LUTS in young men has a variety of underlying etiologies and VUDS in this population is helpful in attaining an accurate diagnosis and thus may guide toward efficient management.}, } @article {pmid36504399, year = {2023}, author = {Fuchs, H and Padilla-Cabal, F and Oborn, BM and Georg, D}, title = {Commissioning a beam line for MR-guided particle therapy assisted by in silico methods.}, journal = {Medical physics}, volume = {50}, number = {2}, pages = {1019-1028}, doi = {10.1002/mp.16143}, pmid = {36504399}, issn = {2473-4209}, mesh = {*Protons ; *Proton Therapy/methods ; Computer Simulation ; Magnetic Resonance Imaging/methods ; Monte Carlo Method ; Water ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; }, abstract = {BACKGROUND: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry.

PURPOSE: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations.

METHODS: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract high-quality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data.

RESULTS: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area.

CONCLUSION: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of-the art dose calculation methods.}, } @article {pmid36504339, year = {2022}, author = {Ambrose, JM and Veeraraghavan, VP and Vennila, R and Rupert, S and Sathyanesan, J and Meenakshisundaram, R and Selvaraj, S and Malayaperumal, S and Kullappan, M and Dorairaj, S and Gujarathi, JR and Gandhamaneni, SH and Surapaneni, KM}, title = {Comparison of mammosphere formation from stem-like cells of normal breast, malignant primary breast tumors, and MCF-7 cell line.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {34}, number = {1}, pages = {51}, pmid = {36504339}, issn = {2589-0409}, support = {F1-17.1/2013-14/MANF-2013-14-CHR-TAM-25064//University Grants Commission/ ; }, mesh = {Humans ; Female ; MCF-7 Cells ; *Breast ; *Breast Neoplasms ; Neoplastic Stem Cells ; }, abstract = {BACKGROUND: Mammosphere formation assay has become a versatile tool to quantify the activity of putative breast cancer stem cells in non-adherent in vitro cultures. However, optimizing the suspension culture system is crucial to establish mammosphere cultures from primary breast tumors.

METHODS: This study aimed at determining the self-renewal and sphere-forming potential of breast cancer stem-like cells derived from human primary invasive ductal carcinoma and normal breast tissue samples, and MCF-7 breast cancer cell line using an optimal suspension culture system. Mammosphere-forming efficiency of the mammospheres generated from the tissue samples and cell line were compared. We evaluated the expression of CD44[+]/CD24[-]/[low] and CD49f[+]/EpCAM[-]/[low] phenotypes in the stem-like cells by flow cytometry. CK-18, CK-19, α-SMA, and EpCAM marker expression was assessed using immunohistochemical staining.

RESULTS: Breast epithelial cells isolated from the three samples formed two-dimensional spheroids in suspension cultures. Interestingly, mammospheres formed from patient-derived primary breast tumors were enriched in breast cancer stem-like cells with the phenotype CD44[+]/CD24[-]/[low] and exhibited a relatively more number of large spheres when compared to the normal breast stem cells. MCF-7-derived SCs were more aggressive and resulted in the formation of a significantly higher number of spheroids. The expression of CK-18/CK-19 and α-SMA/EpCAM proteins was confirmed in breast cancer tissues.

CONCLUSIONS: Thus, the use of primary tumor specimens and breast cancer cell lines as suitable models for elucidating the breast cancer stem cell activity was validated using mammosphere culture system.}, } @article {pmid36501121, year = {2022}, author = {Leikin-Frenkel, A and Schnaider Beeri, M and Cooper, I}, title = {How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501121}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Blood-Brain Barrier/metabolism ; alpha-Linolenic Acid/metabolism ; Brain/metabolism ; Apolipoprotein E4/genetics/metabolism ; }, abstract = {Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.}, } @article {pmid36482277, year = {2023}, author = {Udayasiri, RI and Luo, T and Gorringe, KL and Fox, SB}, title = {Identifying recurrences and metastasis after ductal carcinoma in situ (DCIS) of the breast.}, journal = {Histopathology}, volume = {82}, number = {1}, pages = {106-118}, doi = {10.1111/his.14804}, pmid = {36482277}, issn = {1365-2559}, support = {GNT2002944//Cancer Australia/ ; IIRS-18-051//National Breast Cancer Foundation/ ; GNT1193630//National Health and Medical Research Council/ ; //Peter MacCallum Cancer Foundation/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumour that has the potential to progress to invasive ductal carcinoma (IDC). Thus, it represents a treatment dilemma: alone it does not present a risk to life, however, left untreated it may progress to a life-threatening condition. Current clinico-pathological features cannot accurately predict which patients with DCIS have invasive potential, and therefore clinicians are unable to quantify the risk of progression for an individual patient. This leads to many women being over-treated, while others may not receive sufficient treatment to prevent invasive recurrence. A better understanding of the molecular features of DCIS, both tumour-intrinsic and the microenvironment, could offer the ability to better predict which women need aggressive treatment, and which can avoid therapies carrying significant side-effects and such as radiotherapy. In this review, we summarise the current knowledge of DCIS, and consider future research directions.}, } @article {pmid36481204, year = {2023}, author = {Chen, J and Yang, Y and Luo, B and Wen, Y and Chen, Q and Ma, R and Huang, Z and Zhu, H and Li, Y and Chen, Y and Qian, D}, title = {Further predictive value of lymphovascular invasion explored via supervised deep learning for lymph node metastases in breast cancer.}, journal = {Human pathology}, volume = {131}, number = {}, pages = {26-37}, doi = {10.1016/j.humpath.2022.11.007}, pmid = {36481204}, issn = {1532-8392}, mesh = {Humans ; Female ; Lymphatic Metastasis/pathology ; *Breast Neoplasms/pathology ; *Deep Learning ; Breast ; Prognosis ; *Lymphoma/pathology ; Lymph Nodes/pathology ; Retrospective Studies ; }, abstract = {Lymphovascular invasion, specifically lymph-blood vessel invasion (LBVI), is a risk factor for metastases in breast invasive ductal carcinoma (IDC) and is routinely screened using hematoxylin-eosin histopathological images. However, routine reports only describe whether LBVI is present and does not provide other potential prognostic information of LBVI. This study aims to evaluate the clinical significance of LBVI in 685 IDC cases and explore the added predictive value of LBVI on lymph node metastases (LNM) via supervised deep learning (DL), an expert-experience embedded knowledge transfer learning (EEKT) model in 40 LBVI-positive cases signed by the routine report. Multivariate logistic regression and propensity score matching analysis demonstrated that LBVI (OR 4.203, 95% CI 2.809-6.290, P < 0.001) was a significant risk factor for LNM. Then, the EEKT model trained on 5780 image patches automatically segmented LBVI with a patch-wise Dice similarity coefficient of 0.930 in the test set and output counts, location, and morphometric features of the LBVIs. Some morphometric features were beneficial for further stratification within the 40 LBVI-positive cases. The results showed that LBVI in cases with LNM had a higher short-to-long side ratio of the minimum rectangle (MR) (0.686 vs. 0.480, P = 0.001), LBVI-to-MR area ratio (0.774 vs. 0.702, P = 0.002), and solidity (0.983 vs. 0.934, P = 0.029) compared to LBVI in cases without LNM. The results highlight the potential of DL to assist pathologists in quantifying LBVI and, more importantly, in exploring added prognostic information from LBVI.}, } @article {pmid36479602, year = {2022}, author = {Lee, HJ and Kang, SW and Lee, JE and Jeong, WG and Lee, JS and Park, MH and Lim, HS}, title = {Malignant Apocrine Lesions of the Breast: Multimodality Imaging Findings and Biologic Features.}, journal = {Journal of breast cancer}, volume = {25}, number = {6}, pages = {513-521}, pmid = {36479602}, issn = {1738-6756}, abstract = {The apocrine morphology of the breast is observed in a broad pathological spectrum, ranging from benign cysts to invasive carcinomas. However, the number of clinical research investigating malignant apocrine lesions is limited. This study retrospectively reviewed the data of patients with malignant apocrine lesions admitted in a tertiary center between January 2004 and December 2021, based on the radiology-pathology correlation and the recent advances in their status to enhance the therapeutic implications of androgen receptor (AR). Among the 37 patients with lesions, 27 (73.0%) had triple-negative subtypes with predominant AR expression. The radiological features of malignant apocrine lesions did not differ from those of typical invasive ductal carcinoma or ductal carcinoma in situ. This study demonstrated that knowledge on the imaging features of malignant apocrine lesions and their histological basis could enhance the adoption of new targeted therapies in patients with this particular type of breast cancer.}, } @article {pmid36478904, year = {2023}, author = {Wu, D and Yu, J and Guo, L and Wei, X and Tian, Z and Duan, X}, title = {Analysis of primary synchronous breast invasive ductal carcinoma and lung adenocarcinoma with next-generation sequencing: A case report.}, journal = {Oncology letters}, volume = {25}, number = {1}, pages = {18}, pmid = {36478904}, issn = {1792-1082}, abstract = {Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.}, } @article {pmid36473870, year = {2022}, author = {Sandbank, J and Bataillon, G and Nudelman, A and Krasnitsky, I and Mikulinsky, R and Bien, L and Thibault, L and Albrecht Shach, A and Sebag, G and Clark, DP and Laifenfeld, D and Schnitt, SJ and Linhart, C and Vecsler, M and Vincent-Salomon, A}, title = {Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {129}, pmid = {36473870}, issn = {2374-4677}, abstract = {Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone. Artificial Intelligence (AI)-based tools can support cancer detection and classification in breast biopsies ensuring rapid, accurate, and objective diagnosis. We present here the development, external clinical validation, and deployment in routine use of an AI-based quality control solution for breast biopsy review. The underlying AI algorithm is trained to identify 51 different types of clinical and morphological features, and it achieves very high accuracy in a large, multi-site validation study. Specifically, the area under the receiver operating characteristic curves (AUC) for the detection of invasive carcinoma and of ductal carcinoma in situ (DCIS) are 0.99 (specificity and sensitivity of 93.57 and 95.51%, respectively) and 0.98 (specificity and sensitivity of 93.79 and 93.20% respectively), respectively. The AI algorithm differentiates well between subtypes of invasive and different grades of in situ carcinomas with an AUC of 0.97 for invasive ductal carcinoma (IDC) vs. invasive lobular carcinoma (ILC) and AUC of 0.92 for DCIS high grade vs. low grade/atypical ductal hyperplasia, respectively, as well as accurately identifies stromal tumor-infiltrating lymphocytes (TILs) with an AUC of 0.965. Deployment of this AI solution as a real-time quality control solution in clinical routine leads to the identification of cancers initially missed by the reviewing pathologist, demonstrating both clinical utility and accuracy in real-world clinical application.}, } @article {pmid36472800, year = {2023}, author = {Chang, YS and Tu, SJ and Chen, HD and Hsu, MH and Chen, YC and Chao, DS and Chung, CC and Chou, YP and Chang, CM and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Integrated genomic analyses of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {17}, number = {1}, pages = {97-111}, pmid = {36472800}, issn = {1936-0541}, support = {DMR-111-135//China Medical University Hospital/ ; MOST-109-2320-B-039-052//Ministry of Science and Technology (TW)/ ; MOST-110-2321-B-039-002//Ministry of Science and Technology (TW)/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Liver Neoplasms/genetics/pathology ; Mutation ; Genomics ; Gene Expression Profiling ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.

METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.

RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+ Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+ memory T cells, CD8+ Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.

CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.}, } @article {pmid36472710, year = {2023}, author = {Tohi, Y and Ishikawa, R and Kato, T and Miyakawa, J and Matsumoto, R and Mori, K and Mitsuzuka, K and Inokuchi, J and Matsumura, M and Shiga, K and Naito, H and Kohjimoto, Y and Kawamura, N and Inoue, M and Kinoshita, H and Hashimoto, K and Goto, K and Haba, R and Kakehi, Y and Sugimoto, M}, title = {Clinical outcomes of intraductal carcinoma or cribriform in radical prostatectomy specimens of men opting for active surveillance: data from the PRIAS-JAPAN study.}, journal = {International journal of clinical oncology}, volume = {28}, number = {2}, pages = {299-305}, pmid = {36472710}, issn = {1437-7772}, mesh = {Male ; Humans ; Prostate/pathology/surgery ; *Prostatic Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Magnetic Resonance Imaging ; Japan ; Prospective Studies ; Watchful Waiting ; Prostatectomy ; Neoplasm Grading ; }, abstract = {BACKGROUND: Among early stage prostate cancer patients, intraductal carcinoma of the prostate (IDC-P) and invasive cribriform are key prognostic factors; however, their presence and clinical significance following active surveillance (AS) are unknown. In men who opted for AS, we aimed to examine the presence and impact of IDC-P or cribriform, utilizing radical prostatectomy (RP) specimens.

METHODS: We re-reviewed 137 RP specimens available in the PRIAS-JAPAN prospective cohort between January 2010 and September 2020. We assessed the presence of IDC-P or cribriform, and compared the patients' characteristics and prostate-specific antigen (PSA) recurrence-free survival after RP between groups with and without IDC-P or cribriform. In addition, we examined the predictive factors associated with IDC-P or cribriform.

RESULTS: The percentage of patients with IDC-P or cribriform presence was 34.3% (47 patients). IDC-P or cribriform pattern was more abundant in the higher Gleason grade group in RP specimens (P < 0.001). The rates of PSA recurrence-free survival were significantly lower in the IDC-P or cribriform groups than in those without them (log rank P = 0.0211). There was no association between IDC-P or cribriform on RP with the Prostate Imaging-Reporting and Data System (PI-RADS) 4,5 score on magnetic resonance imaging (MRI) before RP even with adjustments for other covariates (OR, 1.43; 95% confidence interval [CI] 0.511-3.980, P = 0.497).

CONCLUSIONS: IDC-P or cribriform comprised approximately one-third of all RP specimens in men who underwent RP following AS, confirming their prognostic significance.}, } @article {pmid36472640, year = {2023}, author = {Maalmi, H and Strom, A and Petrera, A and Hauck, SM and Strassburger, K and Kuss, O and Zaharia, OP and Bönhof, GJ and Rathmann, W and Trenkamp, S and Burkart, V and Szendroedi, J and Ziegler, D and Roden, M and Herder, C and , }, title = {Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy.}, journal = {Diabetologia}, volume = {66}, number = {3}, pages = {579-589}, pmid = {36472640}, issn = {1432-0428}, mesh = {Adult ; Humans ; Biomarkers ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2 ; *Diabetic Neuropathies/diagnosis ; Intermediate Filaments ; *Polyneuropathies/diagnosis/complications ; }, abstract = {AIMS/HYPOTHESIS: No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

METHODS: This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.

RESULTS: DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.

CONCLUSIONS/INTERPRETATION: Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.}, } @article {pmid36472055, year = {2022}, author = {Ortiz-Rey, JA and Bellas-Pereira, A and San Miguel-Fraile, P and Morellón-Baquera, R and Domínguez-Arístegui, P and González-Carreró Fojón, J}, title = {Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {9}, pages = {738-745}, doi = {10.56434/j.arch.esp.urol.20227509.108}, pmid = {36472055}, issn = {0004-0614}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/genetics/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Prostatectomy ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/surgery ; }, abstract = {OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.

MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.

RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.

CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.}, } @article {pmid36469156, year = {2023}, author = {Gao, SL and Wang, DY and Wang, X and Zhang, B and Du, F and Ju, J and Yue, J and Kang, YK and Wang, X and Xu, BH and Yuan, P}, title = {Prognostic factors and adjuvant systemic therapy for patients with HER2-positive T1N0 breast cancer: evidence from a real-world study with long-term follow-up.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {3}, pages = {569-582}, pmid = {36469156}, issn = {1573-7217}, support = {No. 81672634//National Natural Science Foundation of China/ ; No. 82172650//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; Adjuvants, Immunologic/therapeutic use ; Anthracyclines/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/pathology ; Chemotherapy, Adjuvant/adverse effects ; Disease-Free Survival ; Follow-Up Studies ; Prognosis ; Receptor, ErbB-2 ; Trastuzumab ; }, abstract = {PURPOSE: The optimal adjuvant systemic treatment and potential prognostic factors for patients with T1N0 HER2-positive breast cancer are still unclear. We conducted a real-world study in this relatively low-risk population to identify the clinical-pathological factors of potential prognostic value and to compare the efficacy of different adjuvant strategies.

METHODS: We included patients with HER2-positive T1N0 breast cancer of infiltrating ductal carcinoma (IDC) histology treated at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2010 to April 2017. We performed Cox multivariate analysis to identify the potential prognostic factors for invasive disease-free survival (IDFS). We also compared survival outcomes of (1) patients treated with adjuvant chemotherapy alone, or chemotherapy plus trastuzumab, or observation; (2) patients receiving adjuvant anthracycline-based and non-anthracycline regimens, both combined with trastuzumab. Inverse probability of treatment weighting (IPTW) propensity score was used to reduce selection bias.

RESULTS: Overall, 692 consecutive patients were included, with a median follow-up of 78.0 months for IDFS. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab were identified as independent prognostic factors. For adjuvant treatment, compared with observation and chemotherapy alone, chemotherapy plus trastuzumab could significantly benefit patients (HR = 2.70, P = 0.034; HR = 3.95, P < 0.001). Meanwhile, compared with observation, chemotherapy alone did not significantly benefit patients (HR = 1.37, P = 0.424). For the comparison of anthracycline-based versus non-anthracycline regimens when combined with trastuzumab, patients in both groups had similar IDFS (HR = 1.74, P = 0.242).

CONCLUSIONS: HER2-positive T1N0 IDC patients could benefit from adjuvant chemotherapy plus trastuzumab. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab are independent prognostic factors for this population.}, } @article {pmid36468069, year = {2022}, author = {Amboni, M and Ricciardi, C and Adamo, S and Nicolai, E and Volzone, A and Erro, R and Cuoco, S and Cesarelli, G and Basso, L and D'Addio, G and Salvatore, M and Pace, L and Barone, P}, title = {Machine learning can predict mild cognitive impairment in Parkinson's disease.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1010147}, pmid = {36468069}, issn = {1664-2295}, abstract = {BACKGROUND: Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI).

AIM: Finding significant features associated with PD-MCI through a machine learning approach.

PATIENTS AND METHODS: Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model.

RESULTS: Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2.

CONCLUSIONS: This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.}, } @article {pmid36465358, year = {2022}, author = {Li, ZX and Chen, JX and Zheng, ZJ and Cai, WJ and Yang, XB and Huang, YY and Gong, Y and Xu, F and Chen, YS and Lin, L}, title = {TGF-β1 promotes human breast cancer angiogenesis and malignant behavior by regulating endothelial-mesenchymal transition.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1051148}, pmid = {36465358}, issn = {2234-943X}, abstract = {BACKGROUND: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-β and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism.

METHODS: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-β1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-β1 on breast cancer progression.

RESULTS: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-β1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-β1 induced EndMT by activation of TGF-β and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-β and Notch signaling pathways.

CONCLUSION: Our findings elucidated the mechanism of TGF-β1 in the promotion of angiogenesis and progression by EndMT in breast cancer.}, } @article {pmid36459596, year = {2022}, author = {Birnbaum, GE and Bachar, T and Levy, GF and Zholtack, K and Reis, HT}, title = {Put Me in Your Shoes: Does Perspective-Taking Inoculate Against the Appeal of Alternative Partners?.}, journal = {Journal of sex research}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00224499.2022.2150998}, pmid = {36459596}, issn = {1559-8519}, abstract = {People commit to monogamous relationships with the intent of maintaining sexual exclusivity but often fail to do so. Existing research has focused on individual and relationship characteristics that render relationships more vulnerable to infidelity, paying less attention to strategies that decrease the likelihood of straying. Three experiments investigated the impact of one strategy that might encourage people to enact relationship-protective responses toward alternative partners, perspective-taking. In all studies, participants either adopted the perspective of their partner or not and then evaluated, encountered, or thought about attractive strangers, in Studies 1-3, respectively. Participants' pro-relationship orientation and reactions during these experiences (interest in alternative and current partners, commitment to current relationships, and fantasmatic themes) were recorded. Results showed that perspective-taking decreased sexual and romantic interest in alternatives, while increasing commitment and desire for current partners. These findings suggest that partner perspective-taking discourages engagement in behaviors that may hurt partners and damage the relationship with them.}, } @article {pmid36452681, year = {2022}, author = {Devi, A and Narwal, A and Kamboj, M and Gupta, M and Pandiar, D and Gupta, A}, title = {Low Grade Intraductal Carcinoma of Palate: An Extremely Rare Entity with Review of Literature.}, journal = {Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India}, volume = {74}, number = {Suppl 2}, pages = {2222-2227}, pmid = {36452681}, issn = {2231-3796}, abstract = {Low-grade intraductal carcinoma (LG-IDC) is the new World Health Organization designation for tumors previously called "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma". LG-IDC is a rare low grade malignant salivary gland neoplasm. A 56-year old woman presented with a painless swelling on the right posterior part of palate of 2 months duration. Radiographic examination revealed heterogenously enhancing soft tissue mass on right side of palate. A provisional diagnosis of pleomorphic adenoma was executed and local excision was done. The tumor had a typical feature of intraductal growth pattern composed of low grade ductal epithelial cells with cribriform and micropapillary patterns forming true "Roman bridges". Immunohistochemically myoepithelial cells displayed p63 around all tumor islands. The case was diagnosed as LG-IDC. LG-IDC is an extremely rare entity and awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment.}, } @article {pmid36451999, year = {2022}, author = {Göker, M and Denys, H and van de Vijver, K and Braems, G}, title = {Genomic assays for lobular breast carcinoma.}, journal = {Journal of clinical and translational research}, volume = {8}, number = {6}, pages = {523-531}, pmid = {36451999}, issn = {2424-810X}, abstract = {BACKGROUND: One of the current challenges in breast cancer is the appropriate treatment of invasive lobular breast cancer (ILC) and defining the high-risk group within ILC. The biological character of ILC typically translates to a good prognosis, however, several studies have indicated that the long-term prognosis is worse than for patients diagnosed with the more commonly invasive ductal carcinoma. Many genomic tests are now available to determine whether those patients are at high risk (HR) and enable tailored treatment. Unfortunately, most of the studies in which these genomic tests have been evaluated entail retrospective analysis of a prospective trial.

AIM: This review focuses on the validation of the available genomic assays based on trials performed in ILC patients, where in some instances, the various subtypes of ILC (classical, pleomorphic, and non-classic type) were taken into account.

RESULTS: Using Oncotype DX in retrospective studies, only 1.3%-8% of ILC tumors were categorized as HR tumors. For MammaPrint, 24% of patients were classified as HR, which was associated with poor outcome. In a recent sub-analysis of the MINDACT study comprising 487 ILC patients, 16.2% were high genomic risk. EndoPredict, Prosigna Breast Cancer Prognostic Gene Signature Assay, and the Breast Cancer Index have been validated in patients receiving only endocrine treatment.

CONCLUSION: Although ILC accounts for the second most common breast cancer subtype in women, none of these tests encompass tumor morphology in their algorithms. Prospective studies on ILC with genomic assays are warranted given the various subtypes of and treatment options for this underestimated, but frequently occurring cancer.

RELEVANCE FOR PATIENTS: Genomic assays can be employed in ILC patients to predict the risk of recurrence and identify those patients who might benefit from chemotherapy in addition to their standard treatment regimen.}, } @article {pmid36447634, year = {2023}, author = {Imai, J and Hanamura, T and Kawanishi, A and Ueda, T and Mishima, Y and Ito, A and Shirataki, Y and Morimachi, M and Kodama, T and Sato, H and Kaneko, M and Sano, M and Teramura, E and Monma, M and Tsuda, S and Tsuruya, K and Mizukami, H and Arase, Y and Fujisawa, M and Miyahara, S and Nakamura, N and Suzuki, T and Matsushima, M and Suzuki, H and Takashimizu, S and Kagawa, T and Nishizaki, Y}, title = {A case of breast cancer with extensive colon metastasis.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e189}, pmid = {36447634}, issn = {2692-4609}, abstract = {Breast cancer is one of the most common malignancies in women worldwide. Although most breast cancers are curable, in cases of metastasis, many are often found in the lungs, bones, liver, and central nervous system; however, metastasis to the gastrointestinal tract is rare. Invasive lobular carcinoma, which represents only 5%-10% of breast cancers, has a higher risk of metastasis to the gastrointestinal tract than invasive ductal carcinoma. Here, we report a rare case of gastrointestinal metastasis of invasive lobular carcinoma that spread extensively to the colonic mucosa. Given the improved survival rates of breast cancer patients with current treatments, many rarer metastatic diseases, including gastrointestinal metastases, are likely to be increased in the future.}, } @article {pmid36444584, year = {2022}, author = {Shahi, V and Agarwal, P and Qayoom, S and Kumar, V and Tewari, S and Raghuvanshi, S and Singh, US and Goel, MM}, title = {Detection of Epstein Barr Nuclear Antigen-1 (EBNA-1), Early Antigen 1F, 2R (EA-1F, EA- 2R) along with Epstein-Barr virus Latent Membrane Protein 1 (LMP1) in Breast Cancer of Northern India: An Interim Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {11}, pages = {3717-3723}, pmid = {36444584}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms ; Herpesvirus 4, Human/genetics ; *Epstein-Barr Virus Infections/complications ; Reproducibility of Results ; Epstein-Barr Virus Nuclear Antigens ; India/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Ductal ; }, abstract = {INTRODUCTION: Worldwide, breast cancer (BC) is a prominent cause of death, with a disproportionately high incidence in developed countries. Epstein-Barr virus (EBV) infection has been reported in up to 90% of the world's population. Although the exact link of EBV infection and breast carcinoma is not yet determined. The present study was carried out to assess the pathological correlation of EBV infection and BC in women from Northern India.

METHODOLOGY: In this prospective observational study, 130 patients with histologically proven breast carcinoma were included. After detailed histology, the paraffin block with infiltrative tumor was selected for molecular analysis and further immunohistochemistry (IHC)- EBV PCR and Epstein-Barr virus latent membrane protein 1 (LMP1) IHC.

RESULTS: Most of the patients were diagnosed with Infiltrating Ductal Carcinoma not otherwise specified (IDC-NOS), followed by Infiltrating Ductal Carcinoma + Ductal Carcinoma in situ (IDC + DCIS). The total of 25 tissues of breast carcinoma had positive EBV PCR results (19.23%). The co-relation between the molecular and immunohistochemical results was significant in 11/25 cases that showed immunoexpression for LMP1 by IHC. Sensitivity of 44% and specificity of 100% were observed for LMP1 IHC, having a PPV value of 100% and an NPV of 88%. No significant correlation was observed between age, tumor subtype, grade, stage with respect to EBV infection; however, there was a significant association with nodal metastasis with extra nodal extension in tumors that had EBV infection.

CONCLUSION: The present study establishes an association between LMP1 and patients with EBV positive breast cancer. The authors suggest that additional multicentric studies be conducted to strengthen the reliability and generalizability of the observations of the current study.}, } @article {pmid36443093, year = {2022}, author = {Burkoň, P and Selingerová, I and Slavik, M and Holánek, M and Vrzal, M and Kazda, T and Hůlková, V and Blažková, M and Poláchová, K and Šlampa, P}, title = {Adjuvant accelerated partial-breast irradiation of early-stage breast cancer using stereotactic approach - methodology, technical challenges and early results of prospective randomized trial.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {35}, number = {5}, pages = {379-391}, doi = {10.48095/ccko2022379}, pmid = {36443093}, issn = {1802-5307}, mesh = {Humans ; Aged ; Middle Aged ; Female ; *Breast Neoplasms/radiotherapy/surgery ; Prospective Studies ; Mastectomy ; Adjuvants, Immunologic ; Radiotherapy, Adjuvant ; }, abstract = {BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects.

MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients.

RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group.

CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.}, } @article {pmid36441068, year = {2023}, author = {Pahouja, G and Patel, HD and Desai, S and Rac, G and Cheng, T and Okabe, Y and Gorbonos, A and Quek, ML and Flanigan, RC and Picken, MM and Gupta, GN}, title = {The rising incidence of ductal adenocarcinoma and intraductal carcinoma of the prostate: Diagnostic accuracy of biopsy, MRI-visibility, and outcomes.}, journal = {Urologic oncology}, volume = {41}, number = {1}, pages = {48.e11-48.e18}, doi = {10.1016/j.urolonc.2022.09.025}, pmid = {36441068}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/diagnostic imaging/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Magnetic Resonance Imaging ; Incidence ; Retrospective Studies ; *Prostatic Neoplasms/diagnostic imaging/surgery ; }, abstract = {INTRODUCTION: Ductal adenocarcinoma (DA) and intraductal carcinoma (IDC) of the prostate are associated with higher stage disease at radical prostatectomy (RP). We evaluated diagnostic accuracy of biopsy, MRI-visibility, and outcomes for patients undergoing RP with DA/IDC histology compared to pure acinar adenocarcinoma (AA) of the prostate.

MATERIALS AND METHODS: A retrospective cohort study of men receiving RP between 2014 and 2021 revealing AA, DA, or IDC on final pathology was conducted. Multivariable logistic regression and Cox proportional hazards regression models were employed.

RESULTS: A total of 609 patients were included with 103 found to have DA/IDC. Patients with DA/IDC were older and had higher PSA, biopsy grade group (GG), RP GG, and other pathologic findings (extraprostatic extension, lymphovascular invasion, perineural invasion, pN stage) compared to AA patients (all P < 0.05). On multivariable analysis, higher age, RP GG, and pT3a were associated with DA/IDC on RP (all P < 0.05). Sensitivity and specificity of biopsy compared to RP for diagnosis of DA/IDC was 29.1% (16.7% DA, 27.8% IDC) and 96.6% (99.3% DA, 96.6% IDC), respectively. In a subset of 281 men receiving MRI, PI-RADS distribution was similar for patients with DA/IDC vs. AA (90.7% vs. 80.7% with PI-RADS 4-5 lesions, P = 0.23) with slightly higher biopsy sensitivity (41.9%). DA/IDC was associated with worse BCR (HR = 1.77, P = 0.02) but not biopsy DA/IDC (P = 0.90).

CONCLUSIONS: Sensitivity of prostate biopsy was low for detection of DA/IDC histology at RP. Patients with DA/IDC histology had unfavorable pathologic features at RP and worse BCR. Of patients with DA/IDC at RP, 90.7% were categorized as PI-RADS 4 to 5 on preoperative MRI.}, } @article {pmid36434575, year = {2022}, author = {Gupta, RB and Dang, H and Albreiki, D and Dollin, ML and Weston, B and Gottlieb, CC}, title = {Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.}, journal = {BMC ophthalmology}, volume = {22}, number = {1}, pages = {452}, pmid = {36434575}, issn = {1471-2415}, mesh = {Humans ; Female ; Fluorescein Angiography/methods ; *Retinal Diseases/complications/diagnosis ; Tomography, Optical Coherence/methods ; Vision Disorders ; Acute Disease ; Atrophy ; *Breast Neoplasms/complications/diagnosis ; }, abstract = {BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma.

CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3 weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation.

CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.}, } @article {pmid36433714, year = {2023}, author = {Xie, T and Jiang, T and Zhao, Q and Fu, C and Nickel, MD and Peng, W and Gu, Y}, title = {Model-Free and Model-based Parameters Derived From CAIPIRINHA-Dixon-TWIST-VIBE DCE-MRI: Associations With Prognostic Factors and Molecular Subtypes of Invasive Ductal Breast Cancer.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {58}, number = {1}, pages = {81-92}, doi = {10.1002/jmri.28533}, pmid = {36433714}, issn = {1522-2586}, support = {SHDC2020CR2008A//Clinical Research Plan of Shanghai Hospital Development Center/ ; 61731008//National Natural Science Foundation of China/ ; 82071878//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/diagnostic imaging/pathology ; Prognosis ; Prospective Studies ; Contrast Media ; Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {BACKGROUND: CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) dynamic contrast-enhanced MRI (DCE-MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model-free and model-based parameters has not been investigated.

PURPOSE: To compare model-free and model-based parameters of CDTV DCE-MRI with both clinicopathologic factors and molecular subtypes of IDC.

STUDY TYPE: Prospective.

POPULATION: A total of 152 patients (mean age, 52 years) with IDC including 42 luminal A, 64 luminal B, 22 human epidermal growth factor receptor-2 (HER2) positive, and 24 triple-negative subtypes.

FIELD STRENGTH/SEQUENCE: A 3 T; turbo-FLASH, Dixon VIBE, and CDTV.

ASSESSMENT: Model-free parameters (initial enhancement rate [IER] and maximum slope [MS]) were estimated from the time-intensity curve. The mean, minimum, maximum, and range between the minimum and maximum values of inline model-based parameters (K[trans] , kep , and ve) were measured to assess intratumoral heterogeneity of IDC lesions.

STATISTICAL TESTS: Student's t tests, Mann-Whitney U tests, Kruskal-Wallis tests, post hoc Steel-Dwass tests, and receiver operating characteristic (ROC) curves. P < 0.05 was considered significant.

RESULTS: No significant differences in IER and MS values were seen among the clinicopathologic factors and molecular subtypes (Bonferroni-corrected P = 0.011-0.862, P = 0.145-0.601, respectively). The minimum kep values in HER2-positive IDC were significantly lower than those in HER2-negative IDC. The mean and range kep values were independent predictors for distinguishing the high (grade 3) and low (grade 1 or 2) nuclear grade groups according to multivariable analyses. The post hoc test showed that the kep minimum and kep range values were significantly different between luminal A and HER2-positive tumor subtypes, yielding an area-under-the-curve of 0.820.

DATA CONCLUSION: Compared with the model-free parameters, inline kep related model-based parameters on CDTV DCE-MRI can be applied as a feasible tool to differentiate luminal A from HER2-positive breast cancers.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.}, } @article {pmid36431454, year = {2022}, author = {Cansever Mutlu, E and Kaya, M and Küçük, I and Ben-Nissan, B and Stamboulis, A}, title = {Exosome Structures Supported by Machine Learning Can Be Used as a Promising Diagnostic Tool.}, journal = {Materials (Basel, Switzerland)}, volume = {15}, number = {22}, pages = {}, pmid = {36431454}, issn = {1996-1944}, support = {University of Birmingham, College of Engineering and Physical Science//University of Birmingham, College of Engineering and Physical Science/ ; }, abstract = {Principal component analysis (PCA) as a machine-learning technique could serve in disease diagnosis and prognosis by evaluating the dynamic morphological features of exosomes via Cryo-TEM-imaging. This hypothesis was investigated after the crude isolation of similarly featured exosomes derived from the extracellular vehicles (EVs) of immature dendritic cells (IDCs) JAWSII. It is possible to identify functional molecular groups by FTIR, but the unique physical and morphological characteristics of exosomes can only be revealed by specialized imaging techniques such as cryo-TEM. On the other hand, PCA has the ability to examine the morphological features of each of these IDC-derived exosomes by considering software parameters such as various membrane projections and differences in Gaussians, Hessian, hue, and class to assess the 3D orientation, shape, size, and brightness of the isolated IDC-derived exosome structures. In addition, Brownian motions from nanoparticle tracking analysis of EV IDC-derived exosomes were also compared with EV IDC-derived exosome images collected by scanning electron microscopy and confocal microscopy. Sodium-Dodecyl-Sulphate-Polyacrylamide-Gel-Electrophoresis (SDS-PAGE) was performed to separate the protein content of the crude isolates showing that no considerable protein contamination occurred during the crude isolation technique of IDC-derived-exosomes. This is an important finding because no additional purification of these exosomes is required, making PCA analysis both valuable and novel.}, } @article {pmid36430783, year = {2022}, author = {Swindell, WR and Bojanowski, K and Chaudhuri, RK}, title = {Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430783}, issn = {1422-0067}, support = {N/A//Sytheon/ ; }, mesh = {Humans ; *Dermatitis, Atopic/drug therapy ; Cytokines ; Fatty Acids ; Isosorbide ; Tumor Necrosis Factor-alpha/pharmacology ; Plant Oils ; Oleic Acid ; }, abstract = {Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.}, } @article {pmid36428573, year = {2022}, author = {Gulde, S and Foscarini, A and April-Monn, SL and Genio, E and Marangelo, A and Satam, S and Helbling, D and Falconi, M and Toledo, RA and Schrader, J and Perren, A and Marinoni, I and Pellegata, NS}, title = {Combined Targeting of Pathogenetic Mechanisms in Pancreatic Neuroendocrine Tumors Elicits Synergistic Antitumor Effects.}, journal = {Cancers}, volume = {14}, number = {22}, pages = {}, pmid = {36428573}, issn = {2072-6694}, support = {314061271-TRR 205-B11//Deutsche Forschungsgemeinschaft/ ; 70113629//German Cancer Aid/ ; 2017.073.2 and 2017.012.1//Wilhelm Sander Stiftung/ ; KFS-4227-08-2017//Swiss Cancer Research Foundation/ ; }, abstract = {Pancreatic neuroendocrine neoplasms (PanNENs) are the second most common malignancy of the pancreas. Surgery remains the only curative treatment for localized disease. For patients with inoperable advanced or metastatic disease, few targeted therapies are available, but their efficacy is unpredictable and variable. Exploiting prior knowledge on pathogenetic processes involved in PanNEN tumorigenesis, we tested buparlisib (PI3K inhibitor) and ribociclib (CDK4/6 inhibitor), as single agents or in combination, in different preclinical models. First, we used cell lines representative of well-differentiated (INS-1E, NT-3) and poorly differentiated (BON-1) PanNENs. The combination of buparlisib with ribociclib reduced the proliferation of 2D and 3D spheroid cultures more potently than the individual drugs. Buparlisib, but not ribociclib, induced apoptosis. The anti-proliferative activity of the drugs correlated with downstream target inhibition at mRNA and protein levels. We then tested the drugs on primary islet microtissues from a genetic PanNET animal model (Men1-defective mice) and from wild-type mice: the drug combination was effective against the former without altering islet cell physiology. Finally, we treated PanNET patient-derived islet-like 3D tumoroids: the combination of buparlisib with ribociclib was effective in three out of four samples. Combined targeting of PI3K and CDK4/6 is a promising strategy for PanNENs spanning various molecular and histo-pathological features.}, } @article {pmid36420892, year = {2023}, author = {Naito, Y and Kato, M and Kawanishi, H and Yamamoto, A and Sakamoto, F and Hirabayashi, H and Kobayashi, M and Matsukawa, Y and Kimura, T and Araki, H and Nishikimi, T and Kondo, A and Yoshino, Y and Hashimoto, Y and Nakano, Y and Tsuzuki, T}, title = {Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer.}, journal = {The Prostate}, volume = {83}, number = {4}, pages = {307-315}, doi = {10.1002/pros.24462}, pmid = {36420892}, issn = {1097-0045}, mesh = {Male ; Humans ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; Androgen Antagonists/therapeutic use ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Retrospective Studies ; Hormones/therapeutic use ; }, abstract = {BACKGROUND: In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC.

METHODS: This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching.

RESULTS: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264).

CONCLUSIONS: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.}, } @article {pmid36420590, year = {2022}, author = {Roberts, AC and Lunt, LG and Coogan, AC and Madrigrano, A}, title = {The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.}, journal = {The American surgeon}, volume = {}, number = {}, pages = {31348221135780}, doi = {10.1177/00031348221135780}, pmid = {36420590}, issn = {1555-9823}, abstract = {Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.}, } @article {pmid36419161, year = {2022}, author = {Philippson, C and Larsen, S and Simon, S and Vandekerkhove, C and De Caluwe, A and Van Gestel, D and Chintinne, M and Veys, I and De Neubourg, F and Noterman, D and Roman, M and Nogaret, JM and Desmet, A}, title = {Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {83}, pmid = {36419161}, issn = {1465-542X}, mesh = {Humans ; Female ; *Mastectomy, Segmental ; Electrons ; *Breast Neoplasms/radiotherapy/surgery/pathology ; Prospective Studies ; Follow-Up Studies ; Neoplasm Recurrence, Local/radiotherapy ; Registries ; }, abstract = {BACKGROUND: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial.

METHODS: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical).

RESULTS: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%.

CONCLUSIONS: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.}, } @article {pmid36414494, year = {2023}, author = {Zhang, C and Liang, Z and Feng, Y and Xiong, Y and Manwa, C and Zhou, Q}, title = {Risk Factors for Lymphovascular Invasion in Invasive Ductal Carcinoma Based on Clinical and Preoperative Breast MRI Features: a Retrospective Study.}, journal = {Academic radiology}, volume = {30}, number = {8}, pages = {1620-1627}, doi = {10.1016/j.acra.2022.10.029}, pmid = {36414494}, issn = {1878-4046}, mesh = {Humans ; Retrospective Studies ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {RATIONALE AND OBJECTIVES: Lymphovascular invasion (LVI) plays an important role in the prediction of metastasis and prognosis in breast cancer (BC) patients. The present study assessed correlations between preoperative breast MRI, clinical features, and LVI in patients with invasive ductal carcinoma (IDC) and identified risk factors based on these correlation factors.

MATERIALS AND METHODS: Patients confirmed with IDC between 01/2012 and 12/2021 were retrospectively reviewed at our hospital. A total of 5 clinical and 14 MRI features to characterize tumours were extracted. LVI evaluated in hematoxylin and eosin sections. T-test and chi-square tests were used to compare the differences in clinical and MRI features between the LVI positive and negative groups. The associations between individual features and LVI were analysed by univariable logistic regression analysis, and risk factors for LVI were identified by multivariable logistic regression analysis based on these correlation factors.

RESULTS: This study included 353 patients with IDC, including 130 with positive LVI. Age, CEA, CA-153, amount of fibroglandular tissue (FGT), background parenchymal enhancement, tumour size, shape, skin thickening, nipple retraction, adjacent vessel sign, and axillary lymph node (ALN) size in the LVI positive group were significantly different from the LVI negative group (all p<0.05). Multivariate logistic regression analysis revealed that age (odds ratio OR = 1.030), CA-153 (OR = 1.018), heterogeneous FGT (OR = 2.484), shape (OR = 2.157), and ALN size (OR = 1.051) were risk factors for LVI (all p<0.05).

CONCLUSION: Preoperative breast MRI and clinical features correlated with LVI, age, CA-153, heterogeneous FGT, shape, and ALN size are risk factors for LVI in patients with IDC.}, } @article {pmid36412445, year = {2022}, author = {Karaman, H and Senel, F and Tasdemir, A and Özer, I and Dogan, M}, title = {A single centre experience in Turkey for comparison between core needle biopsy and surgical specimen evaluation results for HER2, SISH, estrogen receptors and progesterone receptors in breast cancer patients.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1789-1795}, doi = {10.4103/jcrt.JCRT_601_20}, pmid = {36412445}, issn = {1998-4138}, mesh = {Female ; Humans ; Male ; Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnosis ; *Carcinoma ; In Situ Hybridization ; Receptors, Estrogen ; Receptors, Progesterone ; Retrospective Studies ; Silver ; Turkey ; }, abstract = {BACKGROUND: Breast carcinoma diagnosis can be made with core-needle biopsy (CNB), but there are controversies regarding the evaluation of hormone receptor (HR) status in needle biopsy specimens. When preoperative neoadjuvant therapy is required in breast cancer cases, the CNB specimen should be evaluated to decide on the treatment.

OBJECTIVES: In this study, we aimed to compare the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and silver in situ hybridization (SISH) results of the CNB specimens and surgical specimens (SS) of our breast carcinoma cases.

MATERIALS AND METHODS: This retrospective study included cases diagnosed with breast cancer in our center for approximately 1 year between 2017 and 2018. About 97 cases with both CNB specimens and SS were included in the study. Data such as the ER, PR, HER2, and SISH evaluation results in CNB and SS, age distribution and histopathological type, metastatic lymph nodes, lymphovascular invasion, tumor size, and grade of the tumor were recorded. The data were analyzed using SPSS 22.0 (Statistical Package for the Social Sciences, Armonk, NY, USA) software.

RESULTS: All of the cases were female and 70.1% of them were aged over 45. About 27.8% of the cases were aged 31-45 years, and 2.1% were aged under 30. When evaluated according to the histopathological type of the tumor, 71.1% of cases were invasive ductal carcinoma (IDC), 8.2% were invasive lobular carcinoma (ILC), 6.2% were IDC + ILC, 11.3% were another carcinoma, and 3.1% were in situ carcinoma. 12.4% of the cases were Grade I, 43.3% were Grade II, and 20.6% were Grade III. 43.3% of our cases' tumor size were ≤2 cm and 56.7% >2 cm. 50 (51.5%) of these cases had no lymph node metastasis. It was found out that 36 (37.1%) of the cases had 1-4 metastatic lymph nodes and 11 (11.3%) of them had 5 and more metastatic lymph nodes. It was found out that 44 (45.4.%) of the cases had no lymphovascular invasion and 53 (54.6%) of them had a lymphovascular invasion. When HR statuses in CNB and SS were compared, ER was found to have a sensitivity of 96.1% and a specificity of 100%. PR was found to have a sensitivity of 94.2% and a specificity of 66.7%. HER2 was found to have a sensitivity of 100% and a specificity of 73.4%.

CONCLUSION: ER evaluation results are reliable in deciding on needle biopsy material. PR may show the heterogeneous distribution in HER2 tumor. Thus, if PR and HER2 results in needle biopsy material are negative, assessments should be repeated in SS.}, } @article {pmid36412439, year = {2022}, author = {Abbas, Z and Nouroz, F and Ejaz, S}, title = {Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1743-1753}, doi = {10.4103/jcrt.JCRT_1310_20}, pmid = {36412439}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Genes, BRCA1 ; BRCA1 Protein/genetics ; *Carcinoma/genetics ; *Antineoplastic Agents ; }, abstract = {BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.

AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.

MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.

RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.

CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.}, } @article {pmid36411355, year = {2022}, author = {Kalyan, VSRK and Meena, S and Karthikeyan, S and Jawahar, D}, title = {Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.}, journal = {Archives of microbiology}, volume = {204}, number = {12}, pages = {721}, pmid = {36411355}, issn = {1432-072X}, support = {E28ACC//Science and Engineering Research Board/ ; }, mesh = {*Siderophores ; *Soil ; India ; Bacteria/genetics ; Iron Chelating Agents ; }, abstract = {The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.}, } @article {pmid36406197, year = {2022}, author = {Albores-Mendez, EM and Casanas-Pimentel, RG and Reyes-Chacon, IR and Maldonado Cubas, J and Lopez-Cruz, J and Rincon-Huerta, JA and Camacho-Ibarra, A and San Martin-Martinez, E}, title = {Cancer Progression Is not Different in Mice of Different Gender Inoculated With Cells of the Triple-Negative 4T1 Breast Cancer Model.}, journal = {World journal of oncology}, volume = {13}, number = {5}, pages = {249-258}, pmid = {36406197}, issn = {1920-454X}, abstract = {BACKGROUND: Breast cancer in men is a rare and poorly studied disease, and its treatment is based on women breast cancer studies. However, clinical outcome is not the same in men and women. Basic studies and clinical trials in animal models provide detailed information on cancer, origin, development, cell signaling pathways, sites of metastasis, and target molecules. It is necessary to explore the biology of breast cancer in male animal models that allow observing their similarity.

METHODS: The triple-negative 4T1 breast cancer model was developed in both male and female mice and studied weekly during 4 weeks. For that, twenty 8-week-old female and male BALB/c mice were used. Sixteen mice (eight males and eight females) were inoculated into the second left thoracic mammary pad with 20,000 4T1 cells, resuspended in 20 µL phosphate-buffered saline (PBS). All samples were processed for immunodetection, characterized histopathologically and immunohistochemically.

RESULTS: In this work, we describe the development of a triple-negative 4T1 breast cancer model in male BALB/c mice. Breast tumors were characterized histopathologically at different time points and corresponded to a moderately differentiated invasive ductal carcinoma, estrogen receptor ER-/progesterone receptor PR-/human epidermal growth factor receptor 2 HER2-/Ki67+, with histological grade II (moderately differentiated; a solid mass with occasional duct formation and moderate to severe nuclear pleomorphism), infiltrating the adipose and muscular tissue, and metastasis to lungs. From the results, we did not observe differences in the time of tumor development, necrosis, color change of tumor tissue, and lung metastasis between male and female mice. Even though we did not find histological differences, response to treatment and molecular signaling may be different.

CONCLUSIONS: The histogenesis of male breast tumors was similar to that of female BALB/c mice. The histological and immunohistochemical characteristics of male tumors also match the features reported for stage IV human breast cancer of men and women. The murine male breast cancer model described here can be a significant tool to explore the molecular mechanisms involved in male breast cancer tumorigenesis and metastasis and may bring new approaches for clinical treatment of triple-negative breast cancer in men.}, } @article {pmid36399606, year = {2023}, author = {Gao, G and Epstein, JI}, title = {High-Grade Desmoplastic Foamy Gland Prostatic Adenocarcinoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {147}, number = {9}, pages = {1039-1049}, doi = {10.5858/arpa.2022-0165-OA}, pmid = {36399606}, issn = {1543-2165}, mesh = {Male ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Prostate/surgery/pathology ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/pathology ; Prostatectomy ; Biopsy, Needle ; }, abstract = {CONTEXT.—: It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and death.

OBJECTIVE.—: To review the morphology, immunohistochemistry, and prognosis for this rare subtype of prostate adenocarcinoma.

DESIGN.—: Twenty-four cases received for consultation from 2010 to 2021 were analyzed including needle biopsy (n = 21), transurethral resection (n = 2), and a cystoprostatectomy (n = 1).

RESULTS.—: Patients ranged in age from 40 to 89 years (mean, 67 years). On average, 8 cores per case were involved (mean 67% core involvement). Extraprostatic extension and seminal vesicle invasion were observed in 6 of 21 (29%) and 3 of 21 (14%) needle biopsy cases, respectively. Twenty of the 24 cases (83%) were Grade Group (GG) 5 with 4 of 24 (17%) being GG4. Tumor necrosis as a component of Gleason pattern 5 was observed in 21 of 24 cases (88%). Associated intraductal adenocarcinoma (IDC) was observed in 22 of 24 cases (92%), with 4 of 24 cases (17%) demonstrating extensive IDC. Diagnostic challenges were as follows: (1) sparse isolated cancer glands embedded in the dense desmoplastic stroma; (2) fragmented glands; and (3) aberrant staining for high-molecular-weight cytokeratin in a nonbasal cell pattern in all cases. PTEN loss was observed in 9 cases, and p53 nuclear accumulation was observed in 8 cases. Three patients were lost to follow-up. Overall, of the 16 patients with meaningful follow-up, 12 (75%) either had metastases or died from prostate cancer.

CONCLUSIONS.—: High-grade desmoplastic foamy gland adenocarcinoma is difficult to diagnose and grade and has a poor prognosis.}, } @article {pmid36398701, year = {2022}, author = {Kant, V}, title = {'The spirit is willing, but the flesh is weak?': systemic unknown-knowns for ergonomics in India.}, journal = {Ergonomics}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/00140139.2022.2149851}, pmid = {36398701}, issn = {1366-5847}, abstract = {While the worldwide ergonomics community increases its sophistication in solving global problems, specific systemic challenges still plague Indians in urban mega-cities such as Mumbai. This paper aims to highlight the gaps using the knowns-unknowns framework, which exists in the Indian ergonomics community's capability to address such systemic challenges. Within this framework, the epistemological category of 'unknown-knowns' is explicated further using a case study of urban accidental deaths and injuries in Mumbai, India. These systemic casualties are essential to note because they are not only hidden from public awareness but can be avoided by proper ergonomics interventions. The article concludes with four main directions for the Indian ergonomics community in solving systemic problems in terms of, (a) capacity-building, (b) advocacy; (c) developing all realms of ergonomics with particular emphasis on complex systems; (d) developing India-centric pathways for ergonomics as a discipline. Practitioner's summary: This paper aims to highlight gaps in the academic Indian ergonomics community's capacity to solve public systemic problems. An India-centric way forward for awareness, engagement, and academic capacity building is suggested to develop a comprehensive national ergonomics mission.}, } @article {pmid36396676, year = {2022}, author = {Contrepois, K and Chen, S and Ghaemi, MS and Wong, RJ and Jehan, F and Sazawal, S and Baqui, AH and Stringer, JSA and Rahman, A and Nisar, MI and Dhingra, U and Khanam, R and Ilyas, M and Dutta, A and Mehmood, U and Deb, S and Hotwani, A and Ali, SM and Rahman, S and Nizar, A and Ame, SM and Muhammad, S and Chauhan, A and Khan, W and Raqib, R and Das, S and Ahmed, S and Hasan, T and Khalid, J and Juma, MH and Chowdhury, NH and Kabir, F and Aftab, F and Quaiyum, A and Manu, A and Yoshida, S and Bahl, R and Pervin, J and Price, JT and Rahman, M and Kasaro, MP and Litch, JA and Musonda, P and Vwalika, B and Shaw, G and Stevenson, DK and Aghaeepour, N and Snyder, MP}, title = {Author Correction: Prediction of gestational age using urinary metabolites in term and preterm pregnancies.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19753}, doi = {10.1038/s41598-022-23715-7}, pmid = {36396676}, issn = {2045-2322}, support = {001/WHO_/World Health Organization/International ; }, } @article {pmid36395590, year = {2022}, author = {Lin, Z and He, Y and Qiu, C and Yu, Q and Huang, H and Yiwen Zhang, and Li, W and Qiu, T and Xiaoping Li, }, title = {A multi-omics signature to predict the prognosis of invasive ductal carcinoma of the breast.}, journal = {Computers in biology and medicine}, volume = {151}, number = {Pt A}, pages = {106291}, doi = {10.1016/j.compbiomed.2022.106291}, pmid = {36395590}, issn = {1879-0534}, mesh = {Humans ; *Breast ; Area Under Curve ; ROC Curve ; Risk Factors ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Precisely evaluating the prognosis of invasive ductal carcinoma (IDC) of the breast is challenging as most prognostic signatures use single-omics data based on gene or clinical information.

METHODS: Whole-slide images (WSIs), transcriptome, and clinical data of breast IDC were collected from the Cancer Genome Atlas Database. The cancer-associated fibroblast (CAF) gene sets were downloaded from the Molecular Signatures Database. The WSI feature was extracted by artificial feature engineering. The CAF prognostic genes were determined by the Gene Set Enrichment Analysis, the Wilcoxon test, and univariate Cox regression. The IDC patients were divided into the training and test sets. The prognostic signatures based on WSIs, IDC-CAFs, bi-omics, and tri-omics were constructed using multivariate Cox regression. The samples were divided into low- and high-risk groups according to the median risk score. The Kaplan-Meier survival and receiver operating characteristic curves were applied to validate the prediction performance of the four signatures.

RESULTS: In total, 508 IDC patients with complete data were included. The area under the curve (AUC) of single-omics signature based on WSI characteristics and CAFs was 0.765 and 0.775, whereas the AUC of bi-omics was 0.823. The tri-omics signature based on WSIs, CAFs, and lymph node status demonstrated the best predictive value with an AUC of 0.897.

CONCLUSION: The multi-omics signature based on WSIs, CAFs, and clinical characteristics showed excellent prediction ability in breast IDC patients, whose risk factors can also provide a valuable diagnostic reference for the clinical course.}, } @article {pmid36394689, year = {2023}, author = {Mamtani, A and Grabenstetter, A and Sevilimedu, V and Morrow, M and Gemignani, ML}, title = {Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {417-423}, pmid = {36394689}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Breast/pathology ; }, abstract = {PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.

METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.

RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.

CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.}, } @article {pmid36382077, year = {2022}, author = {Srinivasan, S and Patel, S and Khade, A and Bedi, G and Mohite, J and Sen, A and Poovaiah, R}, title = {Efficacy of a novel augmentative and alternative communication system in promoting requesting skills in young children with Autism Spectrum Disorder in India: A pilot study.}, journal = {Autism & developmental language impairments}, volume = {7}, number = {}, pages = {23969415221120749}, pmid = {36382077}, issn = {2396-9415}, abstract = {Background & aims: The study assessed the efficacy of a novel, child-friendly, socio-culturally sensitive, icon-based Augmentative and Alternative Communication (AAC) system called Jellow Communicator, in teaching requesting skills to young children with Autism Spectrum Disorder (ASD) in a special school in Mumbai, India. Jellow is a comprehensive AAC system with a lexicon and pictorial library designed using a participatory, user-centric design process. The content of Jellow has been developed bearing in mind the socio-cultural and linguistic diversity of India. Jellow is available in low-tech (flashcards, booklet) and high-tech (Android and iOS app and desktop application) versions. Methods: The quasi-experimental longitudinal study involved seventeen 3.5-12-year-old children with ASD with communication challenges. Children were taught to use the Jellow AAC system to request for preferred items, as part of their regular speech therapy sessions. Each child received one-on-one training sessions with a licensed speech therapist twice a week over a 3-month duration, with each session lasting around 20-30 min. A systematic training protocol adapted from the original Picture Exchange Communication System (PECS) was developed to train children to use the Jellow system, progressing from flashcards to the app version of Jellow. Behavioral training strategies such as modeling, least-to-most prompting, differential reinforcement, and behavior chain interruption were used to facilitate requesting behaviors. The speech therapist assessed children's developmental level across multiple domains at pretest and posttest. We coded 3 videos per child, i.e., one early, one mid, and one late training session each, to assess changes in children's stage of communication, spontaneous requesting abilities, level of attention during training trials, and average time to completion for requesting trials. In addition, caregivers filled out questionnaires to assess training-related changes in children's adaptive functioning levels as well as the psychosocial impact of the Jellow AAC system on children's quality of life. Results: Children significantly improved their stage of communication, and a majority of children transitioned from flashcards to using the Jellow app to request for preferred items. Children also increased the proportion of spontaneous requests over the course of training. Caregivers reported a positive perceived psychosocial impact of the Jellow AAC system on their child's self-esteem, adaptability, and competence. Conclusions: The findings from our pilot study support the use of the novel, socio-culturally adapted, Jellow Communicator AAC system for teaching requesting skills to young children with ASD who use multiple communication modalities. Future studies should replicate our findings with a larger group of participants using a randomized controlled trial design. Implications: This is the first experimental study to systematically assess the effects of an indigenously-developed comprehensive AAC system adapted to the sociocultural and linguistic landscape of India. Our study results provide support for the use of the cost-effective Jellow Communicator AAC system in facilitating requesting skills in children with ASD who use multiple communication modalities. Clinicians can use low-tech and high-tech versions of Jellow to promote communication skills in children with ASD.}, } @article {pmid36378000, year = {2022}, author = {Almehmadi, M and Salih, MM and Shafie, A and Alsharif, A and Alsiwiehr, N and El-Askary, A and Alzahrani, K and Al-Hazmi, A and Aljuaid, A and Abdulazziz, O and Almalki, AA and Allahyani, M and Eed, E and Alharbi, AM and Halawi, M and Allam, HH and Abutawil, H and Alosimi, E and Gharib, AF}, title = {Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.}, journal = {Clinical laboratory}, volume = {68}, number = {11}, pages = {}, doi = {10.7754/Clin.Lab.2022.220316}, pmid = {36378000}, issn = {1433-6510}, mesh = {Humans ; Female ; Middle Aged ; SARS-CoV-2 ; Immunoglobulin M ; Seroepidemiologic Studies ; *COVID-19/epidemiology/prevention & control ; BNT162 Vaccine ; *Breast Neoplasms ; COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose.

METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test).

RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups.

CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.}, } @article {pmid36376280, year = {2022}, author = {Haythorne, E and Lloyd, M and Walsby-Tickle, J and Tarasov, AI and Sandbrink, J and Portillo, I and Exposito, RT and Sachse, G and Cyranka, M and Rohm, M and Rorsman, P and McCullagh, J and Ashcroft, FM}, title = {Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6754}, pmid = {36376280}, issn = {2041-1723}, support = {MR/V011979/1/MRC_/Medical Research Council/United Kingdom ; BB/R017220/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Insulin/metabolism ; *Hyperglycemia/metabolism ; Pyruvic Acid/metabolism ; *Islets of Langerhans/metabolism ; *Diabetes Mellitus/metabolism ; }, abstract = {Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.}, } @article {pmid36375403, year = {2023}, author = {Baré, J and Gheddou, A and Kalinowski, MB}, title = {Overview of temporary radioxenon background measurement campaigns conducted for the CTBTO between 2008 and 2018.}, journal = {Journal of environmental radioactivity}, volume = {257}, number = {}, pages = {107053}, doi = {10.1016/j.jenvrad.2022.107053}, pmid = {36375403}, issn = {1879-1700}, mesh = {Xenon Radioisotopes/analysis ; *Air Pollutants, Radioactive/analysis ; *Radiation Monitoring/methods ; International Cooperation ; Nuclear Reactors ; }, abstract = {The Comprehensive Nuclear-Test-Ban Treaty (CTBT) specifies that an overall network of at least 40 International Monitoring System (IMS) stations should monitor the presence of radioxenon in the atmosphere upon its entry into force. The measurement of radioxenon concentrations in the air is one of the major techniques to detect underground nuclear explosions. It is, together with radionuclide particulate monitoring, the only component of the network able to confirm whether an event originates from a nuclear test, leaving the final proof to on-site inspection. Correct and accurate interpretation of radioxenon detections by State Signatories is a key parameter of the verification regime of the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO). In this context, the discrimination between the highly variable radioxenon background generated by normal operations of nuclear facilities and CTBT-relevant events is a challenging, but critical, task. To this end, the radioxenon background that can be expected at IMS noble gas systems must be sufficiently characterized and understood. All activities conducted to study the global radioxenon background are focused on the calibration and performance of the verification system as described in the Treaty. The unique CTBTO noble gas system network is designed to optimally covering the globe. By the end of 2019, 31 systems were put in operation, 25 of which being already certified. It took two decades from the first experimental setup of noble gas system in the field to reach this stage of maturity. In the meantime, it was an urgent need to gain empirical evidence of atmospheric radioxenon concentrations with the full spectrum of characteristics that IMS noble gas systems may be observing. This experience was significantly advanced through temporary measurement campaigns. Their objective was to gain the additional necessary knowledge for a correct understanding and categorization of radioxenon detections. The site selection for these campaigns put emphasis on regions with low coverage by the initially few experimental noble gas systems at IMS locations or where potential interferences with normal background might be observed. Short-term measurements were first initiated in 2008. Sites of potential interest were identified, and campaigns up to few weeks were performed. Based on the findings of these short campaigns, transportable systems were procured by the CTBTO. Longer temporary measurement campaigns were started afterwards and operated by local hosts in different regions of the globe. Site selections were based on purely scientific criteria. Objectives of the measurement campaigns were continually reassessed, and projects were designed to meet the scientific needs for radioxenon background understanding as required for nuclear explosion monitoring. As of today, several thousands of samples have been collected and measured. Spectra of temporary measurement campaigns were (and are still) analysed in the International Data Centre (IDC). As they are not part of the CTBT monitoring system, no IDC product is generated. Analysis results are stored in a non-operational database of the CTBTO and made available, together with raw data, to authorized users of States Signatories through a Secure Web Portal (SWP) and to scientific institutions for approved research projects through a virtual Data Exploitation Centre (vDEC) after signing a cost-free confidentiality agreement (https://www.ctbto.org/specials/vdec). This paper aims at providing an overview of the temporary measurement campaigns conducted by the CTBTO since the very first field measurements. It lays out scientific results in a systematic approach. This overview demonstrates the asset of radioxenon background measurement data that have been collected with a wide variety of characteristics that may be observed at IMS stations. It bears a tremendous opportunity for development, enhancement and validation of methodologies for CTBT monitoring. In 2018, a campaign started in Japan with transportable noble gas systems in the vicinity of the IMS station RN38 in Takasaki. It will be described separately once the measurements are completed.}, } @article {pmid36374375, year = {2023}, author = {Li, J and Sun, B and Li, Y and Li, S and Wang, J and Zhu, Y and Lu, H}, title = {Correlation analysis between shear-wave elastography and pathological profiles in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {269-276}, pmid = {36374375}, issn = {1573-7217}, support = {82172025//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Elasticity Imaging Techniques ; Multivariate Analysis ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: To explore the correlation between shear-wave elastography (SWE) parameters and pathological profiles of invasive breast cancer.

METHODS: A total of 197 invasive breast cancers undergoing preoperative SWE and primary surgical treatment were included. Maximum elastic modulus (Emax), mean elastic modulus (Emean), and elastic modulus standard deviation (Esd) were calculated by SWE. Pathological profile was gold standard according to postoperative pathology. The relationship between SWE parameters and pathological factors were analyzed using univariate and multivariate analysis.

RESULTS: In univariate analysis, large cancers showed significantly higher Emax, Emean and Esd (all P < 0.001). Emax and Esd in the group of histological grade III were higher than those in the group of grade I (both P < 0.05). Invasive lobular carcinomas (ILC) showed higher Emean than invasive ductal carcinoma (IDC) (P < 0.001). Lymphovascular invasion (LVI) group showed higher Emax values than negative group (P < 0.05). Emax, Emean and Esd of the Ki-67 positive group presented higher values than negative group (all P < 0.05). Androgen receptor (AR) positive lesions had lower Esd than AR negative lesions (P < 0.05). In multivariate analysis, invasive size independently influenced Emax (P < 0.001). Invasive size and pathological type both independently influenced Emean (both P < 0.001). Invasive size and AR status were both independently influenced Esd (both P < 0.05).

CONCLUSION: SWE parameters correlated with pathological profiles of invasive breast cancer.In particular, AR positive group showed significantly low Esd than negative group.}, } @article {pmid36372577, year = {2023}, author = {Di Lena, É and Antoun, A and Hopkins, B and Barone, N and Do, U and Meterissian, S}, title = {Sentinel lymph node biopsy in women over 70: Evaluation of rates of axillary staging and impact on adjuvant therapy in elderly women.}, journal = {Surgery}, volume = {173}, number = {3}, pages = {603-611}, doi = {10.1016/j.surg.2022.09.016}, pmid = {36372577}, issn = {1532-7361}, mesh = {Female ; Humans ; Aged ; Sentinel Lymph Node Biopsy ; Lymph Node Excision ; Retrospective Studies ; *Breast Neoplasms/surgery/pathology ; Mastectomy ; Axilla/pathology ; Neoplasm Staging ; *Sentinel Lymph Node/pathology ; }, abstract = {BACKGROUND: The 2016 Society of Surgical Oncology Choosing Wisely guidelines recommended against routine sentinel lymph node biopsy in women ≥70 years old with favorable, early-stage breast cancer, as sentinel lymph node biopsy does not decrease recurrence or mortality in these patients. This study's objective was to evaluate the use of sentinel lymph node biopsy and its effect on management in elderly patients.

METHODS: A retrospective analysis of female patients ≥70 years old with stage I-II, clinically node-negative, hormone-receptor positive, HER2-negative disease undergoing upfront breast cancer surgery between 2017 and 2019. Primary outcome was rate of sentinel lymph node biopsy. Secondary outcome was effect of sentinel lymph node biopsy on adjuvant therapy.

RESULTS: In total, 142 patients were included. Median age was 76 (interquartile range 73-81), and 71.8% underwent lumpectomy. On final pathology, 57.7% had invasive ductal carcinoma, and median tumor size was 15 mm (interquartile range 10-24.3). A total of 118 patients (83.1%) underwent sentinel lymph node biopsy; of these, 27 (22.9%) were positive for N1mi (7 patients) or N1a disease (20 patients). On multivariate regression analysis, patients undergoing sentinel lymph node biopsy were more likely to be younger (odds ratio 0.87, 95% confidence interval 0.78-0.95). The major risk factor for sentinel lymph node biopsy positivity was lymphovascular invasion (odds ratio 13.4, 95% confidence interval 4.57-40.1). Patients with sentinel lymph node biopsy positivity were more likely to receive local adjuvant radiation therapy (odds ratio 4.66, 95% confidence interval 1.49-16.8) and tended to receive more adjuvant regional radiation therapy (75.0% if sentinel lymph node biopsy positive compared with 15.3% if sentinel lymph node biopsy negative, P < .001).

CONCLUSION: Despite the 2016 Choosing Wisely guidelines, more than 80% of patients ≥70 years old underwent sentinel lymph node biopsy at our institution. If sentinel lymph node biopsy was positive, this is associated with over 4-fold higher rates of adjuvant radiation therapy.}, } @article {pmid36369328, year = {2022}, author = {Yang, Y and Gao, D and Xie, X and Qin, J and Li, J and Lin, H and Yan, D and Deng, K}, title = {DeepIDC: A Prediction Framework of Injectable Drug Combination Based on Heterogeneous Information and Deep Learning.}, journal = {Clinical pharmacokinetics}, volume = {61}, number = {12}, pages = {1749-1759}, pmid = {36369328}, issn = {1179-1926}, support = {82130112//the National Natural Science Foundation of China/ ; DFL20190702//the Beijing Excellent Talent Project/ ; }, mesh = {Humans ; *Deep Learning ; Drug Combinations ; Algorithms ; Machine Learning ; Drug Interactions ; }, abstract = {BACKGROUND AND OBJECTIVE: In clinical practice, injectable drug combination (IDC) usually provides good therapeutic effects for patients. Numerous clinical studies have directly indicated that inappropriate IDC generates adverse drug events (ADEs). The clinical application of injections is increasing, and many injections lack relevant combination information. It is still a significant need for experienced clinical pharmacists to participate in evidence-based drug decision making, monitor medication safety, and manage drug interactions. Meanwhile, a large number of injection pairs and dosage combinations limit exhaustive screening. Here, we present a prediction framework, called DeepIDC, that can expediently screen the feasibility of IDCs using heterogeneous information with deep learning. This is the first specific prediction framework to identify IDCs.

METHODS: Since the interaction between the injected drugs may occur in the direct physical and chemical reactions at the time of mixing or may be the indirect interaction of their drug targets and pathways, we used molecular fingerprints, drug-target associations, and drug-pathway associations to convert injections into a string of digital vectors. Then, based on these injection vectors, we combined a bidirectional long short-term memory and a feed-forward neural network to build a prediction model for accurate and instructive prediction of IDC.

RESULTS: In three realistic evaluation scenarios, DeepIDC has achieved ideal prediction results. Furthermore, compared with the other five machine-learning methods, the proposed predictor is more efficient and robust. Among the top 30 potential IDCs of each IDC class predicted by DeepIDC, we found that 9 cases were experimentally verified in the literature or available on Drug.com.

CONCLUSION: The information we extracted in vivo and in vitro can effectively characterize injectable drugs. DeepIDC developed based on deep learning algorithm provides a valuable unified framework for new IDC discovery, which can make up for the lack of IDC information and predict potential IDC events.}, } @article {pmid36365810, year = {2022}, author = {Malik, MS and Zulfiqar, MH and Khan, MA and Mehmood, MQ and Massoud, Y}, title = {Facile Pressure-Sensitive Capacitive Touch Keypad for a Green Intelligent Human-Machine Interface.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {21}, pages = {}, pmid = {36365810}, issn = {1424-8220}, support = {ITL//King Abdullah University of Science and Technology/ ; }, mesh = {Humans ; *Touch ; Electrodes ; Electronics ; *Graphite ; Plastics ; }, abstract = {There is a great demand for human-machine interfaces (HMIs) in emerging electronics applications. However, commercially available plastic-based HMIs are primarily rigid, application-specific, and hard to recycle and dispose of due to their non-biodegradability. This results in electronic and plastic waste, potentially damaging the environment by ending up in landfills and water resources. This work presents a green, capacitive pressure-sensitive (CPS), touch sensor-based keypad as a disposable, wireless, and intelligent HMI to mitigate these problems. The CPS touch keypads were fabricated through a facile green fabrication process by direct writing of graphite-on-paper, using readily available materials such as paper and pencils, etc. The interdigitated capacitive (IDC) touch sensors were optimized by analyzing the number of electrode fingers, dimensions, and spacing between the electrode fingers. The CPS touch keypad was customized to wirelessly control a robotic arm's movements based on the touch input. A low-pressure touch allows slow-speed robotic arm movement for precision movements, and a high-pressure touch allows high-speed robotic arm movement to cover the large movements quickly. The green CPS touch keypad, as a disposable wireless HMI, has the potential to enforce a circular economy by mitigating electronic and plastic waste, which supports the vision of a sustainable and green world.}, } @article {pmid36357456, year = {2022}, author = {Voon, W and Hum, YC and Tee, YK and Yap, WS and Salim, MIM and Tan, TS and Mokayed, H and Lai, KW}, title = {Performance analysis of seven Convolutional Neural Networks (CNNs) with transfer learning for Invasive Ductal Carcinoma (IDC) grading in breast histopathological images.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {19200}, pmid = {36357456}, issn = {2045-2322}, support = {IPSR/RMC/UTARRF/2022-C1/H02//UTAR Research Fund (UTARRF)/ ; FRGS/1/2019/ICT04/UTAR/02/1//Fundamental Research Grant Scheme/ ; }, mesh = {Humans ; *Neural Networks, Computer ; Publications ; Machine Learning ; *Carcinoma, Ductal ; }, abstract = {Computer-aided Invasive Ductal Carcinoma (IDC) grading classification systems based on deep learning have shown that deep learning may achieve reliable accuracy in IDC grade classification using histopathology images. However, there is a dearth of comprehensive performance comparisons of Convolutional Neural Network (CNN) designs on IDC in the literature. As such, we would like to conduct a comparison analysis of the performance of seven selected CNN models: EfficientNetB0, EfficientNetV2B0, EfficientNetV2B0-21k, ResNetV1-50, ResNetV2-50, MobileNetV1, and MobileNetV2 with transfer learning. To implement each pre-trained CNN architecture, we deployed the corresponded feature vector available from the TensorFlowHub, integrating it with dropout and dense layers to form a complete CNN model. Our findings indicated that the EfficientNetV2B0-21k (0.72B Floating-Point Operations and 7.1 M parameters) outperformed other CNN models in the IDC grading task. Nevertheless, we discovered that practically all selected CNN models perform well in the IDC grading task, with an average balanced accuracy of 0.936 ± 0.0189 on the cross-validation set and 0.9308 ± 0.0211on the test set.}, } @article {pmid36357366, year = {2022}, author = {Willemsen, N and Kotschi, S and Bartelt, A}, title = {Fire up the pyre: inosine thermogenic signaling for obesity therapy.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {375}, pmid = {36357366}, issn = {2059-3635}, support = {PROTEOFIT/ERC_/European Research Council/International ; }, mesh = {Humans ; *Bacterial Proteins ; *Signal Transduction ; Inosine ; Obesity/genetics ; }, } @article {pmid36353989, year = {2023}, author = {Vos, DY and Wijers, M and Smit, M and Huijkman, N and Kloosterhuis, NJ and Wolters, JC and Tissink, JJ and Pronk, ACM and Kooijman, S and Rensen, PCN and Kuivenhoven, JA and van de Sluis, B}, title = {Cargo-Specific Role for Retriever Subunit VPS26C in Hepatocyte Lipoprotein Receptor Recycling to Control Postprandial Triglyceride-Rich Lipoproteins.}, journal = {Arteriosclerosis, thrombosis, and vascular biology}, volume = {43}, number = {1}, pages = {e29-e45}, doi = {10.1161/ATVBAHA.122.318169}, pmid = {36353989}, issn = {1524-4636}, mesh = {Animals ; Humans ; Mice ; Hepatocytes/metabolism ; Lipoproteins/metabolism ; *Low Density Lipoprotein Receptor-Related Protein-1/genetics ; Mice, Knockout ; *Proprotein Convertase 9/genetics/metabolism ; Receptors, LDL ; Triglycerides/metabolism ; }, abstract = {BACKGROUND: The copper metabolism MURR1 domains/coiled-coil domain containing 22/coiled-coil domain containing 93 (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to the cell surface of hepatocytes. Impaired functioning of hepatocytic CCC causes hypercholesterolemia in mice, dogs, and humans. Retriever, a protein complex consisting of subunits VPS26C, VPS35L, and VPS29, is associated with CCC, but its role in endosomal lipoprotein receptor transport is unclear. We here investigated the contribution of retriever to hepatocytic lipoprotein receptor recycling and plasma lipids regulation.

METHODS: Using somatic CRISPR/Cas9 gene editing, we generated liver-specific VPS35L or VPS26C-deficient mice. We determined total and surface levels of LDLR and LRP1 and plasma lipids. In addition, we studied the protein levels and composition of CCC and retriever.

RESULTS: Hepatocyte VPS35L deficiency reduced VPS26C levels but had minimal impact on CCC composition. VPS35L deletion decreased hepatocytic surface expression of LDLR and LRP1, accompanied by a 21% increase in plasma cholesterol levels. Hepatic VPS26C ablation affected neither levels of VPS35L and CCC subunits, nor plasma lipid concentrations. However, VPS26C deficiency increased hepatic LDLR protein levels by 2-fold, probably compensating for reduced LRP1 functioning, as we showed in VPS26C-deficient hepatoma cells. Upon PCSK9 (proprotein convertase subtilisin/kexin type 9)-mediated LDLR elimination, VPS26C ablation delayed postprandial triglyceride clearance and increased plasma triglyceride levels by 26%.

CONCLUSIONS: Our study suggests that VPS35L is shared between retriever and CCC to facilitate LDLR and LRP1 transport from endosomes to the cell surface. Conversely, retriever subunit VPS26C selectively transports LRP1, but not LDLR, and thereby may control hepatic uptake of postprandial triglyceride-rich lipoprotein remnants.}, } @article {pmid36350000, year = {2022}, author = {Chen, W and Wang, G and Zhang, G}, title = {Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.}, journal = {Cancer biology & medicine}, volume = {19}, number = {10}, pages = {1487-1495}, pmid = {36350000}, issn = {2095-3941}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Tumor Microenvironment/genetics ; *Carcinoma, Ductal, Breast/pathology ; Biomarkers, Tumor ; *Breast Neoplasms/genetics ; }, } @article {pmid36347469, year = {2022}, author = {Forster, C and Prax, K and Jaensch, P and Müller, S and Hepp, T and Schlager, H and Friedland, K and Zerth, J}, title = {[The Economic Evaluation of the GLICEMIA 2.0 Study as an Example of a Complex Intervention].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {84}, number = {12}, pages = {1165-1173}, doi = {10.1055/a-1924-7672}, pmid = {36347469}, issn = {1439-4421}, mesh = {Humans ; Cost-Benefit Analysis ; *Diabetes Mellitus, Type 2/therapy ; Germany ; Research Design ; }, abstract = {BACKGROUND: A piggyback approach was used to evaluate the cost-effectiveness of the prevention program delivered at the point of care pharmacy in the GLICEMIA 2.0 study that sought to guide participants in the intervention group to improved glycemic control in type 2 diabetes with sustained incentivization of lifestyle changes, therapeutic compliance, and adherence. The control group received passive medication management and monitoring.

METHODS: Primary endpoint of the GLICEMIA 2.0 study was the stabilization of HbA1c values. For health economic evaluation, incremental differences in output changes were examined, defined as the difference in the distribution of the HbA1c values between both groups over time. Direct program costs and anticipated indirect costs of service utilization were used as cost parameters. A net monetary benefit approach was used to validate cost-effectiveness thresholds via the formation of ICER values.

RESULTS: The intervention group had significantly higher reductions in HbA1c-values. Risk stratification of initial HbA1c showed (short-term) cost effectiveness for initially higher HbA1c values. Due to the limited study period, no long-term differences in medical resource utilization could be assessed.

CONCLUSION: The GLICEMIA program indicates considerable effectiveness potentials, especially for high-risk patients. The study design seems to have assisted the intervention group's adherence in contrast to the control group. Detailed impacts within the complex intervention could not be validated due to restrictions of the study design as a complex intervention. Overall, statements about effect sustainability and further utilization rates progressions are limited due to a lack of follow-up.}, } @article {pmid36344177, year = {2022}, author = {Cai, Q and Shah, RB}, title = {Cribriform Lesions of the Prostate Gland.}, journal = {Surgical pathology clinics}, volume = {15}, number = {4}, pages = {591-608}, doi = {10.1016/j.path.2022.07.001}, pmid = {36344177}, issn = {1875-9157}, mesh = {Male ; Humans ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/pathology ; *Prostatic Neoplasms/diagnosis/pathology ; *Precancerous Conditions/pathology ; Diagnosis, Differential ; }, abstract = {"Cribriform lesions of the prostate represent an important and often diagnostically challenging spectrum of prostate pathology. These lesions range from normal anatomical variation, benign proliferative lesions, premalignant, suspicious to frankly malignant and biologically aggressive entities. The concept of cribriform prostate adenocarcinoma (CrP4) and intraductal carcinoma of the prostate (IDC-P), in particular, has evolved significantly in recent years with a growing body of evidence suggesting that the presence of these morphologies is important for clinical decision-making in prostate cancer management. Therefore, accurate recognition and reporting of CrP4 and IDC-P architecture are especially important. This review discusses a contemporary diagnostic approach to cribriform lesions of the prostate with a focus on their key morphologic features, differential diagnosis, underlying molecular alterations, clinical significance, and reporting recommendations."}, } @article {pmid36340971, year = {2022}, author = {Shir-Raz, Y and Elisha, E and Martin, B and Ronel, N and Guetzkow, J}, title = {Censorship and Suppression of Covid-19 Heterodoxy: Tactics and Counter-Tactics.}, journal = {Minerva}, volume = {}, number = {}, pages = {1-27}, pmid = {36340971}, issn = {0026-4695}, abstract = {The emergence of COVID-19 has led to numerous controversies over COVID-related knowledge and policy. To counter the perceived threat from doctors and scientists who challenge the official position of governmental and intergovernmental health authorities, some supporters of this orthodoxy have moved to censor those who promote dissenting views. The aim of the present study is to explore the experiences and responses of highly accomplished doctors and research scientists from different countries who have been targets of suppression and/or censorship following their publications and statements in relation to COVID-19 that challenge official views. Our findings point to the central role played by media organizations, and especially by information technology companies, in attempting to stifle debate over COVID-19 policy and measures. In the effort to silence alternative voices, widespread use was made not only of censorship, but of tactics of suppression that damaged the reputations and careers of dissenting doctors and scientists, regardless of their academic or medical status and regardless of their stature prior to expressing a contrary position. In place of open and fair discussion, censorship and suppression of scientific dissent has deleterious and far-reaching implications for medicine, science, and public health.}, } @article {pmid36339683, year = {2022}, author = {Wang, X and Xue, Y}, title = {Analysis of Prognostic Factors and Construction of Prognostic Models for Invasive Micropapillary Carcinoma of the Breast.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {1072218}, pmid = {36339683}, issn = {1748-6718}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/pathology ; Prognosis ; Retrospective Studies ; *Carcinoma, Papillary/therapy ; *Breast Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: To compare and analyze the clinical characteristics of invasive micropapillary carcinoma (IMPC) of the breast (IMPC-B) and invasive ductal carcinoma (IDC) of the breast (IDC-B) and establish a prognostic model of IMPC-B.

METHODS: We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 and screened 581 patients with IMPC and 1325 patients with IDC. We compared age, race, laterality, tumor site, histological grade, type of surgery, radiation, chemotherapy, whether the first primary tumor, T stage, N stage, M stage, and molecular type between IMPC-B and IDC-B and draw survival curves of IMPC-B and IDC-B. The relationship between clinical factors and prognosis was investigated by univariate analysis using the Log-rank test and multivariate analysis of the Cox proportional hazards regression model. A risk scoring model was constructed based on independent risk factors to distinguish high-risk and low-risk patients; in addition, a nomogram was created to predict patient survival.

RESULTS: There were differences between the two groups in the age of onset, race, tumor site, histological grade, type of surgery, N stage, and molecular type (p < 0.05). Overall survival was decreased in IMPC-B compared with IDC-B (p < 0.05). The prognosis of IMPC-B was significantly correlated with histological grade, whether the first primary tumor, type of surgery, radiotherapy, chemotherapy, T stage, and N stage. Based on the relationship between the above factors and overall survival prognosis, the risk score model we constructed can effectively distinguish high-risk and low-risk patients (p < 0.05). The established nomogram had better performance in predicting survival in patients with IMPC-B (C - index = 0.78).

CONCLUSION: IMPC-B has a worse prognosis than IDC-B, with earlier age of onset, higher histological grade, and later N stage, and luminal breast cancer is the main type. The nomogram can well predict the prognosis of patients with IMPC-B, which has a high clinical reference value and provides a scientific basis for clinical treatment.}, } @article {pmid36338724, year = {2022}, author = {Zhao, YY and Xiang, QM and Chen, JL and Zhang, L and Zheng, WL and Ke, D and Shi, RS and Yang, KW}, title = {SLC25A25-AS1 over-expression could be predicted the dismal prognosis and was related to the immune microenvironment in prostate cancer.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {990247}, pmid = {36338724}, issn = {2234-943X}, abstract = {It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.}, } @article {pmid36335424, year = {2022}, author = {Mekheal, E and Kania, BE and Kumari, P and Kumar, V and Maroules, M}, title = {Gynecomastia and Malignancy: A Case of Male Invasive Ductal Breast Carcinoma Treated with Neoadjuvant Chemotherapy.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e937370}, pmid = {36335424}, issn = {1941-5923}, mesh = {Humans ; Male ; Female ; Neoadjuvant Therapy ; *Breast Neoplasms/pathology ; Receptors, Progesterone/therapeutic use ; Receptor, ErbB-2 ; Receptors, Estrogen/therapeutic use ; Mastectomy ; *Breast Neoplasms, Male/surgery ; *Gynecomastia/etiology/drug therapy/surgery ; Estrogens/therapeutic use ; *Carcinoma, Ductal/drug therapy/surgery ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Chemotherapy, Adjuvant ; }, abstract = {BACKGROUND Male breast cancer represents a rare malignancy with identifiable risk factors, including genetics, radiation exposure, liver dysfunction, and concomitant diagnosis of Klinefelter syndrome. Gynecomastia can commonly present in these patients, and despite increased estrogen levels in adipose breast tissue, gynecomastia has not been proven to be a significant risk factor for carcinoma development. Male patients with new-onset breast masses are recommended to undergo diagnostic mammograms and breast ultrasound for further evaluation. Those diagnosed with breast cancer most commonly have invasive ductal carcinoma of the breast, and over half of these patients are found to have estrogen and progesterone receptor (ER/PR) positivity. CASE REPORT In this case report, we present a Black man with gynecomastia and an areolar lesion for a 6-month duration following a traumatic event. He was initially referred to the surgical team for further evaluation, and subsequent imaging and biopsy data revealed ER/PR-positive invasive ductal carcinoma. Multidisciplinary discussions were held, and the patient was arranged to begin neoadjuvant treatment with doxorubicin hydrochloride and cyclophosphamide, followed by treatment with paclitaxel (AC-T) chemotherapy, followed by bilateral mastectomy and adjuvant hormonal therapy. CONCLUSIONS The treatment of male breast cancer has remained relatively like that of female breast cancer, which may be due to the limited data in the treatment of male breast cancer. Thus far, studies involving neoadjuvant chemotherapy of female patients have demonstrated promising responses to expand surgical options for patients and possibly decrease the rates of recurrence. Additional studies are warranted to discern optimal therapy for the male patient population.}, } @article {pmid36332363, year = {2022}, author = {Davis, AA and Gerratana, L and Clifton, K and Medford, AJ and Velimirovic, M and Hensing, WL and Bucheit, L and Shah, AN and D'Amico, P and Reduzzi, C and Zhang, Q and Dai, CS and Denault, EN and Bagegni, NA and Opyrchal, M and Ademuyiwa, FO and Bose, R and Gradishar, WJ and Behdad, A and Ma, CX and Bardia, A and Cristofanilli, M}, title = {Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104316}, pmid = {36332363}, issn = {2352-3964}, support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Circulating Tumor DNA/genetics ; Retrospective Studies ; DNA Copy Number Variations ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.

METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.

FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05).

INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.

FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.}, } @article {pmid36328867, year = {2023}, author = {Cha, Y and Lee, S}, title = {Endoscopy-assisted latissimus dorsi muscle flap harvesting technique for immediate breast reconstruction.}, journal = {Annales de chirurgie plastique et esthetique}, volume = {68}, number = {4}, pages = {308-314}, doi = {10.1016/j.anplas.2022.09.004}, pmid = {36328867}, issn = {1768-319X}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/surgery/pathology ; Mastectomy/methods ; *Superficial Back Muscles/surgery ; Cicatrix/surgery ; *Mammaplasty/methods ; Endoscopy/methods ; Postoperative Complications/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: The purpose of this study is to investigate the usefulness of endoscopy-assisted latissimus dorsi muscle flap (LDMF) harvesting in immediate breast reconstruction following partial mastectomy.

MATERIALS AND METHODS: From November 2016 to December 2019, sixteen female breast cancer patients who underwent immediate breast reconstruction following partial mastectomy underwent LDMF harvesting with endoscopic assistance. This surgical technique was carried out with only one subaxillary skin incision without leaving a scar on the back. Patients' demographic characteristics, histopathologic factors, operative data, postoperative complications, and oncologic safety were collected through electronic chart review.

RESULTS: In sixteen patients, LDMFs were harvested successfully using an endoscopy-assisted technique without conversion to an open technique. The mean age of the patients was 48.0±8.0 years, and the mean body mass index was 24.4±3.9kg/m[2]. The most common histologic subtype was invasive ductal carcinoma, with a mean tumor size of 3.2±2.3cm. In terms of LDMF harvesting time, it took 168.4±44.0minutes. The most common postoperative complication, donor site seroma (75%), was managed non-surgically during the outpatient visit. In terms of cosmetic aspects, we've seen a high level of patient satisfaction, especially with scarring.

CONCLUSIONS: Endoscopy-assisted LDMF harvesting technique is safe and useful for breast reconstruction after partial mastectomy. Compared to the conventional open technique, this method does not leave a long scar on the donor site. As a result, it leads to better cosmetic outcomes and improves patient satisfaction.}, } @article {pmid36320968, year = {2022}, author = {Rathod, GB and Desai, KN and Shrivastava, A and Maru, AM}, title = {Correlation of Tumor Budding With Known Clinicopathological, Histomorphological and Hormonal Receptor Status in Patients With Invasive Breast Carcinoma.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29637}, pmid = {36320968}, issn = {2168-8184}, abstract = {Introduction: Tumor blossoming may be a predictive indicator for a variety of cancers. At the invasive origin of the tumor, cells get detached from the original tumor mass. Aims & objectives: Studying breast cancer tumor budding, as well as its link to other prognostic indicators, such as clinicopathological features and hormone receptor status, will be the focus of this study. Materials & methods: Over six years, 110 cases of invasive breast cancer were examined. Ten high-power fields were used to analyze H&E-stained slices for tumor sprouting. It was determined that the tumor buds were divided into low and high grades. Tumor budding and other prognostic factors were compared using the chi-square test. It was considered significant if the p-value was less than or equal to 0.05. Results: There were 110 cases of invasive ductal carcinoma, which accounts for more than half of the total cases (88.18%). A total of 144 tumors were present, of which 74 displayed strong budding and 36 displayed poor budding. A correlation between tumor budding and tumor size, lymph node metastasis, and tumor stage is statistically significant (P = 0.0099). Conclusion: Tumor budding in breast cancer is an easily visible in microscopy, novel prognostic indicator. A new prognostic element may be added to the reporting process.}, } @article {pmid36319039, year = {2022}, author = {Khan, AM and Arjyal, L and Shamaileh, L and Simon, M}, title = {Gemcitabine-induced digital ischaemia in a patient with metastatic breast cancer.}, journal = {BMJ case reports}, volume = {15}, number = {11}, pages = {}, pmid = {36319039}, issn = {1757-790X}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Deoxycytidine ; Ischemia ; Middle Aged ; Gemcitabine ; }, abstract = {A woman in her 50s with HER2 (human epidermal growth factor receptor 2) positive, estrogen/progesterone receptor negative, metastatic invasive ductal carcinoma of the breast, presented with acral cyanosis and severe throbbing pain after recent administration of gemcitabine. She was treated with aspirin, heparin, amlodipine, topical nitroglycerin and analgesics. Gemcitabine was discontinued permanently. She had a gradual recovery except for a small necrotic area over the right 4th digit. However, surgical intervention was avoided.}, } @article {pmid36309875, year = {2022}, author = {Chen, K and Chen, X and Su, Y}, title = {Is conservative treatment a good choice for pediatric intervertebral disc calcification in children?.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {31}, number = {12}, pages = {3324-3329}, pmid = {36309875}, issn = {1432-0932}, mesh = {Humans ; Male ; Female ; Child ; Child, Preschool ; Conservative Treatment ; *Intervertebral Disc Degeneration/diagnostic imaging/therapy/complications ; *Ossification of Posterior Longitudinal Ligament/complications ; Longitudinal Ligaments ; *Calcinosis/diagnostic imaging/therapy/complications ; Magnetic Resonance Imaging ; *Intervertebral Disc/diagnostic imaging/pathology ; *Intervertebral Disc Displacement/complications ; }, abstract = {PURPOSE: Paediatric intervertebral disc calcification (PIDC) is a rare disease, and its aetiology remains unknown. This study aimed to analyse the characteristics and clinical outcomes of patients with PIDC.

METHODS: After applying the exclusion and inclusion criteria, 159 children diagnosed with PIDC were analysed at our hospital between January 2010 and November 2020. Patients' demographic and clinical data were collected, such as sex, pain, duration time, physical examination, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and radiography, computed tomography, and magnetic resonance imaging findings. Patients were followed up for at least 6 months, and radiography or symptoms were evaluated. Fisher's exact test or χ[2]-test was used for statistical analyses.

RESULTS: One hundred and fifty-nine patients were ultimately followed up with for about 12.5 ± 5.8 months. There were 103 male and 56 female, with an average age of 6.08 ± 2.62 years (2 months to 12 years). A total of 109 patients had only one PIDC, 29 patients had two PIDCs, and 21 patients had multiple PIDCs. Thirty patients were found incidentally and were asymptomatic. A total of 106 patients had neck torticollis. Sixteen patients had IDC herniations, fifteen patients had posterior longitudinal ligament calcification, two patients had anterior longitudinal ligament calcification, and 17 patients had herniation of the vertebral canal. All patients underwent conservative treatment, and none underwent surgery. All patients' symptoms resolved after either collar fixation or neck traction.

CONCLUSION: PIDC can be treated conservatively, even when accompanied by herniation, longitudinal ligament calcification, or clinical neck symptoms.

LEVEL OF EVIDENCE: IV.}, } @article {pmid36309195, year = {2022}, author = {Lin, CW and Chiang, MH and Tam, KW}, title = {Treatment of Mammary Paget Disease: A systematic review and meta-analysis of real-world data.}, journal = {International journal of surgery (London, England)}, volume = {107}, number = {}, pages = {106964}, doi = {10.1016/j.ijsu.2022.106964}, pmid = {36309195}, issn = {1743-9159}, mesh = {Humans ; Female ; *Paget's Disease, Mammary/surgery ; Mastectomy ; *Breast Neoplasms/surgery ; Sentinel Lymph Node Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; }, abstract = {BACKGROUND: Because the lesions of mammary Paget disease (MPD) are often limited to the nipple-areolar complex, the extension of optimal tumor excision is inconclusive. Moreover, the risk of potential tumor upstaging is unknown; therefore, the application of sentinel lymph node biopsy (SLNB) is required for analysis. We systematically reviewed the real-world data to evaluate the optimal treatment and potential predictors of poorer prognosis for MPD.

METHODS: The PubMed, Embase, and Cochrane Library databases were searched for relevant studies. Clinical studies were included if they evaluated the outcome of positive rates of SLNB, prognostic risk factors of MPD, and survival outcomes of treatments of interest for MPD, including mastectomy, breast-conserving surgery (BCS) with radiotherapy, and BCS alone.

RESULTS: A total of 38 studies with 24,062 patients were retrieved. Compared with BCS alone (21.2%), mastectomy (5.9%; P < 0.001) and BCS with radiotherapy (8; P = 0.001) had significantly lower local recurrence rates. Patients with palpable tumors (30.2%) had significantly worse prognoses than those with impalpable (3.4%) tumors in metastasis (P < 0.001), and significantly higher local recurrence rates were observed in patients with underlying invasive carcinoma (6.7%) than those with noninvasive carcinoma (4.5%; P = 0.032). The positive rate of SLNB was 17% (95% CI: 0.115-0.226).

CONCLUSION: Except for MPD alone, BCS alone is not recommended for treating MPD with invasive ductal carcinoma and MPD with ductal carcinoma in situ. Moreover, a palpable mass, underlying invasive carcinoma, and positive lymph node status may lead to a poorer prognosis, which may be taken into consideration for the application of SLNB.}, } @article {pmid36308374, year = {2022}, author = {Gautam, P and Feroz, Z and Tiwari, S and Vijayraghavalu, S and Shukla, GC and Kumar, M}, title = {Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {10}, pages = {3481-3490}, pmid = {36308374}, issn = {2476-762X}, support = {R15 CA252997/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/epidemiology/genetics ; Case-Control Studies ; *Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Risk Factors ; }, abstract = {BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.

RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.

CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.}, } @article {pmid36303871, year = {2022}, author = {Al-Saoudi, E and Christensen, MMB and Nawroth, P and Fleming, T and Hommel, EE and Jørgensen, ME and Fleischer, J and Hansen, CS}, title = {Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {891442}, pmid = {36303871}, issn = {1664-2392}, mesh = {Young Adult ; Humans ; *Diabetic Neuropathies/complications ; *Diabetes Mellitus, Type 1/complications ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/complications ; Lipids ; }, abstract = {AIMS/HYPOTHESIS: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).

METHODS: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity".

RESULTS: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing.

CONCLUSIONS/INTERPRETATIONS: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.}, } @article {pmid36299777, year = {2022}, author = {Bealy, MA and Abugooda, AA and Ahmed, RME and Khalil, NAR and Elasbali, AM and Mohamed, GEY and Eltom, FM and Ahmed, H}, title = {Patterns of Immunohistochemical Expression of P53, BCL2, PTEN, and HER2/neu Tumor Markers in Specific Breast Cancer Lesions.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {2026284}, pmid = {36299777}, issn = {1741-427X}, abstract = {OBJECTIVE: This study aimed to associate the expression of P53, BCL2, PTEN, and HER2/neu tumor markers in specific breast cancer lesions.

METHODS: This study analyzed the immunohistochemical expression of P53, BCL2, PTEN, and HER2/neu tumor markers for 306 patients who presented with lesions. Tissue blocks and patients' identification data were retrieved from the department of pathology, AL Madinah Almonwarah hospital, Al Madinah, UAE.

RESULTS: Of the 306 patients, 104 had benign lesions and 202 had malignancy (including 194 females and 6 males). Most females were presented with invasive ductal carcinoma (IDC), followed by infiltrating ductal carcinoma, and invasive lobular carcinoma (ILC), representing 70%, 23.2%, and 3.7%, respectively. Positive P53, BCL2, PTEN, and HER2 were identified in 20.8%, 11.9%, 91%, and 18.3%, respectively.

CONCLUSION: : The expression of P53, BCL2, PTEN, and HER2/neu tumor markers among Saudi patients with breast cancer is relatively similar in many parts of the world.}, } @article {pmid36296007, year = {2022}, author = {Hu, W and Wu, B and Srivastava, SK and Ay, SU}, title = {Comparative Study and Simulation of Capacitive Sensors in Microfluidic Channels for Sensitive Red Blood Cell Detection.}, journal = {Micromachines}, volume = {13}, number = {10}, pages = {}, pmid = {36296007}, issn = {2072-666X}, abstract = {Microfluidics provides an indispensable platform for combining analytical operations such as sample preparation, mixing, separation/enrichment, and detection onto a single compact platform, defined as a lab-on-a-chip (LOC) device with applicability in biomedical and life science applications. Due to its ease of integration, 1D interdigital capacitive (IDC) sensors have been used in microfluidic platforms to detect particles of interest. This paper presents a comparative study on the use of capacitive sensors for microfluidic devices to detect bioparticles, more specifically red blood cells (RBCs). The detection sensitivities of 1D, 2D, and 3D capacitive sensors were determined by simulation using COMSOL Multiphysics[®] v5.5. A water-filled 25 μm × 25 μm PDMS microfluidic channel was used with different sizes (5-10 μm) of red blood cells passing across the capacitive sensor regions. The conformal mapping was used for translating the 1D IDC sensor dimensions into equivalent 2D/3D parallel plate capacitance (PPC) sensor dimensions, creating similar absolute sensor capacitance. The detection sensitivity of each capacitive sensor is determined, and a new 3D PPC sensor structure was proposed to improve the sensitivity for high-resolution RBC detection in microfluidic channels. Proposed 2D and 3D sensors provide a 3× to 20× improvement in sensitivity compared to the standard 1D IDC structures, achieving a 100 aF capacitance difference when a healthy RBC passes in the structure.}, } @article {pmid36291370, year = {2022}, author = {Riskin, Y and Riskin, A and Zaitoon, H and Habib, C and Blanche, E and Gover, A and Mintz, A}, title = {The Effects of Rudeness on NICU Medical Teams Studied by a New Tool for the Assessment of Decision-Making Group Dynamics.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {36291370}, issn = {2227-9067}, abstract = {BACKGROUND: Group decision-making can be placed on a continuum of group dynamics, between Groupthink and Polythink.

OBJECTIVE: To present a new assessment tool for the characterization of medical teams' decision-making group dynamics, and test it to study the effects of exposure to rudeness on various types of group dynamics.

METHODS: Three judges who watched videotapes of critical care simulations evaluated 24 neonatal intensive care unit teams' decision-making processes. Teams were rated using the new assessment tool, especially designed for this quantitative study, based on items adapted from symptoms of Polythink and Groupthink.

RESULTS: Measures of reliability, inter-rater agreement and internal consistency, were reasonably good. Confirmatory factor analysis refined the tool and verified that the symptoms in each category (Polythink or Groupthink) of the refined 14 items' assessment tool were indeed measures of the construct. The average General Score was in the range of the balanced dynamic on the continuum, and without tendency towards one of the extremities (Groupthink or Polythink). No significant effect of exposure to rudeness on group dynamics was found.

CONCLUSIONS: This is a first attempt at using quantitative methods to evaluate decision-making group dynamics in medicine, by adapting symptoms of Groupthink and Polythink as items in a structured assessment tool. It suggests a new approach to understanding decision-making processes of medical teams. The assessment tool seems to be a promising, feasible and reasonably reliable research tool to be further studied in medicine and other disciplines engaged in decision-making.}, } @article {pmid36289427, year = {2022}, author = {Xu, R and Yang, TX and Fang, KW and Wang, G and Li, P}, title = {Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {17905}, pmid = {36289427}, issn = {2045-2322}, mesh = {Humans ; *Botulinum Toxins, Type A ; Urodynamics ; Muscarinic Antagonists/therapeutic use/pharmacology ; *Urinary Bladder, Neurogenic/drug therapy ; Solifenacin Succinate/pharmacology/therapeutic use ; Network Meta-Analysis ; Tolterodine Tartrate/pharmacology ; Bayes Theorem ; Treatment Outcome ; *Urinary Bladder, Overactive/drug therapy ; }, abstract = {To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdetmax endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.}, } @article {pmid36288886, year = {2022}, author = {Takahashi, E and Imai, K and Fukuyama, M and Terata, K and Nanjo, H and Ishiyama, K and Hiroshima, Y and Yatsuyanagi, M and Kudo, C and Morishita, A and Wakita, A and Takashima, S and Sato, Y and Nomura, K and Minamiya, Y}, title = {Changes in Serum Trace Element Concentrations Before and After Surgery in Resectable Breast Cancer.}, journal = {Anticancer research}, volume = {42}, number = {11}, pages = {5323-5334}, doi = {10.21873/anticanres.16039}, pmid = {36288886}, issn = {1791-7530}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Breast Neoplasms/surgery/pathology ; *Carcinoma, Ductal, Breast/surgery/pathology ; Mastectomy ; *Trace Elements ; Vanadium ; Copper ; Boron ; *Selenium ; Titanium ; Reproducibility of Results ; Retrospective Studies ; Biomarkers ; Chromium ; Zinc ; }, abstract = {BACKGROUND/AIM: Minerals and trace elements (TEs) play vital roles in normal biological functions and in all cancers. Breast carcinoma is the most commonly occurring cancer in women. The aim of this study was to evaluate changes in TE levels before and after breast cancer surgery and the clinical utility and reliability of TE levels assayed using inductively coupled plasma mass spectrometry (ICP-MS).

PATIENTS AND METHODS: Thirteen patients with ductal carcinoma in situ (DCIS) and 34 with invasive ductal carcinoma (IDC) treated with planned surgery were enrolled between August 2017 and February 2019. Blood samples were collected before and the day after resection of the primary tumor. All enrolled patients received mastectomy or quadrantectomy and axillary lymph node dissection/biopsy. Serum TE concentrations were determined using ICP-MS.

RESULTS: Changes in boron, titanium, vanadium, chromium, copper, zinc, and selenium levels from before to after surgery differed between IDC and DCIS patients. Boron and copper levels before surgery and changes in titanium, vanadium, and chromium before and after surgery are potential predictors distinguishing DCIS from IDC. Subset analysis showed that chromium is a potential biomarker for luminal subtype, while titanium and chromium are potential biomarkers for pathological staging.

CONCLUSION: Changes in serum TEs before and after surgery may help with diagnosis and staging of breast cancer and in establishing TE supplementation protocols.}, } @article {pmid36284635, year = {2022}, author = {Zhang, H and Yuan, J and Xiang, Y and Liu, Y}, title = {Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {2099327}, pmid = {36284635}, issn = {1687-8450}, abstract = {The incidence of lung adenocarcinoma (LUAD), the most common subtype of lung cancer, continues to make lung cancer the largest cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been shown to have a significant role in both the onset and progression of lung cancer. In this study, we aimed to investigate the clinical significance and underlying mechanism of lncRNA NPSR1-AS1 (NPSR1-AS1) in LUAD. First, we performed an analysis on TCGA and identified 229 differentially expressed lncRNAs (DELs) (including 216 upregulated lncRNAs and 13 downregulated lncRNAs). Then, we carried out a screening of the lncRNAs associated with survival, and a total of 382 survival-related lncRNAs were found. 15 survival-related DELs were identified. Among them, our attention focused on NPSR1-AS1. We found that the expression of NPSR1-AS1 was much higher in LUAD specimens compared to nontumor tissues. According to the results of the ROC assays, high NPSR1-AS1 expression had an AUC value of 0.904 for LUAD, with a 95% confidence interval ranging from 0.881 to 0.927. The expression of NPSR1-AS1 was shown to be significantly elevated in a wide variety of cancers, according to the findings of a pancancer investigation. Functional enrichment analysis confirmed that NPSR1-AS1 was involved in LUAD progression via regulating several tumor-related pathways. Patients with high levels of NPSR1-AS1 expression were shown to have a shorter disease-specific survival (DSS) or overall survival (OS) than those with low levels of NPSR1-AS1 expression, according to the findings of a clinical investigation. It was determined by multivariate analysis that NPSR1-AS1 expressions served as an independent prognostic factor for the overall survival of LUAD patients. The results of immune cell infiltration revealed that the expressions of NPSR1-AS1 were negatively associated with CD8 T cells, pDC, cytotoxic cells, mast cells, iDC, neutrophils, NK CD56dim cells, DC, Th17 cells, Tgd, and macrophages, while they were positively associated with NK CD56bright cells and B cells. Overall, our findings revealed that NPSR1-AS1 could serve as a potential biomarker to assess the clinical outcome and immune infiltration level in LUAD.}, } @article {pmid36283996, year = {2022}, author = {Sanderson, C and Verdellen, C and Debes, N and Tárnok, Z and van de Griendt, J and Zimmerman-Brenner, S and Murphy, T}, title = {Addressing co-occurring conditions in behavioural therapy for tic disorders: a review and guideline.}, journal = {European child & adolescent psychiatry}, volume = {}, number = {}, pages = {}, pmid = {36283996}, issn = {1435-165X}, abstract = {Co-occurring psychiatric conditions are very common in tic disorders and Tourette syndrome. These additional symptoms are often detrimental to quality of life and may impact upon the implementation and efficacy of evidence-based behavioural therapies (BT) for tics. Combining a review of the available literature, relevant theory, and expert clinical practice, we present a guideline for implementing behavioural and psychosocial interventions when common comorbidities are present. These include attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, disruptive behaviour, autism spectrum disorder (ASD) and depression. Practical recommendations are provided for assessment, formulation and management of specific and multiple comorbidities in BT for both children and adults. Despite comorbidities being common in tic disorders, few studies have comprehensively addressed how they may influence the efficacy or implementation of existing therapies or how such treatments may need to be modified or sequenced. We outline recommendations for future research, including randomised control trials of BT for those with specific or multiple comorbidities, as well as adequately powered sub-group analyses within larger scale trials or naturalistic study designs. Transdiagnostic models of psychiatric disorders and treatment, including modular cross-diagnostic therapies, which recognise the dimensionality of psychiatric disorders are also highlighted as an important focus in treatment development in tic disorders.}, } @article {pmid36283257, year = {2022}, author = {Öztürk, Ç and Aşkan, G and Öztürk, SD and Okcu, O and Şen, B and Bedir, R}, title = {Does the number of cell forming tumor budding alter the prognostic value in invasive ductal carcinoma of breast?.}, journal = {Pathology, research and practice}, volume = {240}, number = {}, pages = {154157}, doi = {10.1016/j.prp.2022.154157}, pmid = {36283257}, issn = {1618-0631}, mesh = {Humans ; Female ; Prognosis ; Lymphatic Metastasis/pathology ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; *Carcinoma, Ductal/pathology ; *Carcinoma, Ductal, Breast/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND AND OBJECTIVE: The most commonly used definition for tumor budding (TB) is a single or a cell cluster of tumor cells up to 4 cells. However, there are different opinions regarding the number of cell (NOC) forming TB. It has been proven that TB is associated with poor prognostic factors in most tumors. The current study, it was aimed to investigate the prognostic value of NOC forming TB in invasive ductal carcinoma of the breast.

MATERIALS AND METHODS: 326 cases with the diagnosis of invasive ductal carcinoma were examined. The NOC forming TB was counted from hematoxylin and eosin stained slide under X200 magnification for each case, and scoring five different TB as 1, ≤ 2, ≤ 3, ≤ 4, ≤ 5, respectively. Receiver operating characteristic (ROC) analysis based on survival was performed for each TB value separately, and the cut-off was determined.

RESULTS: All TB values were associated with poor outcome (p < 0.001), presence of distant metastasis (p < 0.001), high Ki67 proliferation index (p < 0.05), advanced stage (p < 0.05), presence of lymphovascular invasion (p < 0.001), and metastatic axillary lymph node (p < 0.001). According to ROC analysis performed to compare the predictiveness of survival, the area under the curve was similar for all TB values.

CONCLUSION: TB was associated with poor prognostic parameters, and the prognostic value of TB was not affected by NOC forming TB. The NOC up to 4 cells which have been accepted for colon carcinomas, could also provide practicality in breast carcinomas.}, } @article {pmid36282904, year = {2022}, author = {Cao, S and Qiu, Y and Unarta, IC and Goonetilleke, EC and Huang, X}, title = {The Ion-Dipole Correction of the 3DRISM Solvation Model to Accurately Compute Water Distributions around Negatively Charged Biomolecules.}, journal = {The journal of physical chemistry. B}, volume = {126}, number = {43}, pages = {8632-8645}, doi = {10.1021/acs.jpcb.2c04431}, pmid = {36282904}, issn = {1520-5207}, mesh = {*Water/chemistry ; Thermodynamics ; Solvents/chemistry ; Solutions/chemistry ; *Nucleotides ; }, abstract = {The 3D reference interaction site model (3DRISM) provides an efficient grid-based solvation model to compute the structural and thermodynamic properties of biomolecules in aqueous solutions. However, it remains challenging for existing 3DRISM methods to correctly predict water distributions around negatively charged solute molecules. In this paper, we first show that this challenge is mainly due to the orientation of water molecules in the first solvation shell of the negatively charged solute molecules. To properly consider this orientational preference, position-dependent two-body intramolecular correlations of solvent need to be included in the 3DRISM theory, but direct evaluations of these position-dependent two-body intramolecular correlations remain numerically intractable. To address this challenge, we introduce the Ion-Dipole Correction (IDC) to the 3DRISM theory, in which we incorporate the orientation preference of water molecules via an additional solute-solvent interaction term (i.e., the ion-dipole interaction) while keeping the formulism of the 3DRISM equation unchanged. We prove that this newly introduced IDC term is equivalent to an effective direct correlation function which can effectively consider the orientation effect that arises from position dependent two-body correlations. We first quantitatively validate our 3DRISM-IDC theory combined with the PSE3 closure on Cl[-], [ClO][-] (a two-site anion), and [NO2][-] (a three-site anion). For all three anions, we show that our 3DRISM-IDC theory significantly outperforms the 3DRISM theory in accurately predicting the solvation structures in comparison to MD simulations, including RDFs and 3D water distributions. Furthermore, we have also demonstrated that the 3DRISM-IDC can improve the accuracy of hydration free-energy calculation for Cl[-]. We further demonstrate that our 3DRISM-IDC theory yields significant improvements over the 3DRISM theory when applied to compute the solvation structures for various negatively charged solute molecules, including adenosine triphosphate (ATP), a short peptide containing 19 residues, a DNA hairpin containing 24 nucleotides, and a riboswitch RNA molecule with 77 nucleotides. We expect that our 3DRISM-IDC-PSE3 solvation model holds great promise to be widely applied to study solvation properties for nucleic acids and other biomolecules containing negatively charged functional groups.}, } @article {pmid36281523, year = {2023}, author = {Chen, MY and Zarrin-Khameh, N and Xu, Y}, title = {Fine needle aspiration of pancreatic lesions focusing on secondary tumors with emphasis of metastatic breast cancer: A clinicopathological study with follow-up.}, journal = {Cancer medicine}, volume = {12}, number = {5}, pages = {5485-5493}, pmid = {36281523}, issn = {2045-7634}, mesh = {Humans ; Female ; Biopsy, Fine-Needle ; *Breast Neoplasms/pathology ; Retrospective Studies ; Follow-Up Studies ; Pancreas/pathology ; *Pancreatic Neoplasms/diagnosis/pathology ; *Carcinoma, Squamous Cell/pathology ; *Carcinoma, Renal Cell/pathology ; *Kidney Neoplasms/pathology ; }, abstract = {BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed as positive for malignancy, 20 (20/274, 7.3%) suspicious for malignancy, and 28 (28/274, 10.2%) cases in the category of neoplastic: other. The most common neoplasm diagnosed was ductal adenocarcinoma (114/274, 41.6%; 114/133, 85.7% in positive for malignancy category). Ten cases (10/274, 3.7%) were diagnosed as metastatic neoplasms to the pancreas, including four breast infiltrating ductal carcinomas (IDC), one endocervical adenocarcinoma, one anal/rectal squamous cell carcinoma, one renal cell carcinoma, one hepatocellular carcinoma, one seminoma and one lung adenocarcinoma. We summarized the biomarkers of the four metastatic breast cancers and conducted literature review on biomarkers of metastatic breast cancers to the pancreas.

CONCLUSIONS: Upon analyzing FNAs of primary and secondary tumors in the pancreas, we have found breast carcinoma is the most common secondary pancreatic neoplasm in our patient population. Triple negative breast ductal carcinoma is the most common tumor among the metastasis of breast carcinomas to the pancreas. To the best of our knowledge, this study is the first report with a literature review focusing on biomarkers of metastatic breast cancer to the pancreas.}, } @article {pmid36276283, year = {2022}, author = {Shen, N and Zhu, S and Zhang, Z and Yong, X}, title = {High Expression of COL10A1 Is an Independent Predictive Poor Prognostic Biomarker and Associated with Immune Infiltration in Advanced Gastric Cancer Microenvironment.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {1463316}, pmid = {36276283}, issn = {1687-8450}, abstract = {Medical technology has become more and more sophisticated recently, which, however, fails to contribute to a better prognosis for patients suffering advanced gastric cancer (GC). Hence, new biomarkers specific to GC diagnosis and prognosis shall be identified urgently. This study screened differentially expressed genes (DEGs) between 375 GC samples and 32 paracancer tissue samples from TCGA datasets. The expression of Collagen type X alpha 1 (COL10A1) in GC was analyzed. The chi-square test assisted in analyzing the relevance of COL10A1 to the clinicopathologic characteristics. The Kaplan-Meier method helped to assess the survival curves and log-rank tests assisted in the examination of the differences. The Cox proportional hazard regression model served for analyzing the risk factors for GC. Then, we developed a nomogram that contained the COL10A1 expression and clinical information. Finally, how COL10A1 expression was associated with the immune infiltration was also evaluated. In this study, 7179 upregulated and 3771 downregulated genes were identified. Among them, COL10A1 expression was distinctly increased in GC specimens compared with nontumor specimens. High COL10A1 expression exhibited an obvious relation to tumor T and pathologic stage. ROC assays confirmed the diagnostic value of COL10A1 expression in screening GC samples from normal samples. Survival data displayed that patients with high COL10A1 expression exhibited a shorter OS and DSS than those with low COL10A1 expression. We obtained a predictive nomogram, which could better predict the COL10A1 expression by virtue of discrimination and calibration. The prognostic value of COL10A1 expression was further confirmed in GSE84426 datasets. Immune assays revealed that COL10A1 expression was associated with tumor-filtrating immune cells, like CD8 T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, NK CD56dim cells, NK cells, pDC, T helper cells, Tem, Th1 cells, Th17 cells, and Treg. Overall, we firstly proved that COL10A1 may be a novel and valuable prognostic and diagnostic factor for GC patients. In addition, COL10A1 has potential to be an immune indicator in GC.}, } @article {pmid36276118, year = {2022}, author = {Wang, Z and Fan, G and Zhu, H and Yu, L and She, D and Wei, Y and Huang, J and Li, T and Zhan, S and Zhou, S and Zhu, Y and Wang, Y and Chen, X and Zhao, J and Zhou, G}, title = {PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {980390}, pmid = {36276118}, issn = {2234-943X}, abstract = {BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.

METHODS: The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.

RESULTS: PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.

CONCLUSION: PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.}, } @article {pmid36275485, year = {2022}, author = {Rehman, B and Mumtaz, A and Sajjad, B and Urooj, N and Khan, SM and Zahid, MT and Mannan, H and Chaudhary, MZ and Khan, A and Parvaiz, MA}, title = {Papillary Carcinoma of Breast: Clinicopathological Characteristics, Management, and Survival.}, journal = {International journal of breast cancer}, volume = {2022}, number = {}, pages = {5427837}, pmid = {36275485}, issn = {2090-3170}, abstract = {OBJECTIVE: To study clinicopathological features, treatment strategies, and prognosis of papillary carcinoma of breast. Material and Methods. Data from 58 patients were retrospectively reviewed from January 2010 to December 2016. Four types of papillary carcinoma (on final resected specimen) were included, i.e., invasive papillary carcinoma (IPC), intracystic (encapsulated) papillary carcinoma (EPC), solid papillary carcinoma (SPC), and papillary DCIS (ductal carcinoma in situ). Various features of the four types were observed and compared.

RESULTS: Of the 58 patients, 8 were males (13.7%). The mean age at presentation was 61 years; the mean tumor size was 33 mm. The frequency of each histological type was as follows: IPC (n = 22/38%), EPC (n = 22/38%), SPC (n = 12/20.6%), and papillary DCIS (n = 2/3.4%). Only two patients were ER negative (both IPC). HER-2 Neu was positive in 3 patients only, out of which 2 died of progressive disease (one EPC and one IPC). LN metastasis was present in 3 (5%) patients (one in each of 1st three types) and only one died of bone metastasis that was also Her-2Neu positive. All patients underwent upfront surgery except two patients who had synchronous IDC on the contralateral side. Breast conservation surgery (BCS) was performed in 34 (58.6%) and mastectomy in 22 (37.9%) patients. 13 patients did not undergo invasive axillary staging; the rest of 43 (74%) patients did (32 sentinel biopsy and 11 axillary dissection). Chemotherapy was given to 18 patients (31%), mostly to IPC (n = 12). Only 2 patients had bone metastasis (one was IPC and one EPC). Cancer-related death was observed in 3 patients. For all groups combined, 5-year OS was 98% and DFS was 92%.

CONCLUSION: Overall, papillary carcinoma of the breast has an excellent prognosis, even though less intense treatment modalities were used. It is still difficult to define the optimum management and avoid overtreatment, given the limited data in the literature.}, } @article {pmid36273358, year = {2022}, author = {Aihara, T and Kumamaru, H and Ishitobi, M and Miyashita, M and Miyata, H and Tamura, K and Yoshida, M and Ogo, E and Nagahashi, M and Asaga, S and Kojima, Y and Kadoya, T and Aogi, K and Niikura, N and Iijima, K and Hayashi, N and Kubo, M and Yamamoto, Y and Takeuchi, Y and Imoto, S and Jinno, H}, title = {Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {196}, number = {3}, pages = {635-645}, pmid = {36273358}, issn = {1573-7217}, mesh = {Humans ; Female ; Receptor, ErbB-2 ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/drug therapy/pathology ; Prognosis ; Chemotherapy, Adjuvant ; }, abstract = {PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer.

METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC.

RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC.

CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.}, } @article {pmid36270911, year = {2023}, author = {Cheng, L and Tariq, H and Yan, L and Reddy, SB and Gattuso, P}, title = {Fine-needle aspiration of intramammary lymph nodes: a clinical, radiographic, and cytologic review.}, journal = {Journal of the American Society of Cytopathology}, volume = {12}, number = {1}, pages = {41-47}, doi = {10.1016/j.jasc.2022.09.004}, pmid = {36270911}, issn = {2213-2945}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Biopsy, Fine-Needle ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Retrospective Studies ; *Fibroadenoma/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; Lymph Nodes/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: Recognizing and sampling intramammary lymph nodes (IMLNs) is important in the clinical management of patients with breast carcinomas. We undertook a retrospective study to evaluate the clinical utility of fine-needle aspiration (FNA) in assessing IMLNs.

MATERIALS AND METHODS: Our pathology database was searched for all IMLN FNA cytology cases from January 2005 to December 2021. The cytologic findings, radiographic features, and clinical data were reviewed.

RESULTS: A total of 149 cases were identified. Eighteen of 149 (12%) patients had synchronous breast tumors, including 13 invasive ductal carcinomas (IDCs), 1 ductal carcinoma in situ (DCIS), and 4 fibroadenomas. Among patients with synchronous IDCs, FNA of IMLNs was positive for metastatic carcinoma in 4 of 13 (30.7%) cases. The 4 patients with positive IMLNs all received mastectomies. Fifteen of 149 (10.7%) patients had a prior history of breast tumors, including 9 IDCs, 4 DCISs, 1 lobular carcinoma in situ (LCIS), and 1 fibroadenoma. Two of 149 (1.3%) patients had a prior history of lymphoma. In the patients with prior history of IDC, DCIS, LCIS, lymphomas and fibroadenomas, IMLN FNAs were all negative for malignancy. Two of 149 cases (1.3%) showed granulomatous lymphadenitis. The remaining 112 cases had negative IMLN FNAs and no significant clinical or pathological findings.

CONCLUSIONS: Our study showed that IMLNs are commonly associated with synchronous/metachronous breast tumors (33 of 149, 22.1%). The incidence of positive IMLN FNA in patients with synchronous invasive breast carcinoma was 30.7% (4 of 13). FNA of IMLNs in conjunction with clinical presentation and radiologic findings allows triage of patients for appropriate clinical management and avoids additional unnecessary surgical procedures.}, } @article {pmid36269831, year = {2022}, author = {Demir, S and Wolff, G and Wieder, A and Maida, A and Bühler, L and Brune, M and Hautzinger, O and Feuchtinger, A and Poth, T and Szendroedi, J and Herzig, S and Ekim Üstünel, B}, title = {TSC22D4 interacts with Akt1 to regulate glucose metabolism.}, journal = {Science advances}, volume = {8}, number = {42}, pages = {eabo5555}, pmid = {36269831}, issn = {2375-2548}, mesh = {Animals ; Mice ; Glucose/metabolism ; Insulin/metabolism ; *Insulin Resistance ; Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; Transcription Factors ; Transforming Growth Factor beta1 ; }, abstract = {Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor-β1 stimulated clone 22 D4 (TSC22D4) as a novel interaction partner for protein kinase B/Akt1, a critical mediator of insulin/phosphatidylinositol 3-kinase signaling pathway. While energy deprivation and oxidative stress promote the TSC22D4-Akt1 interaction, refeeding mice or exposing cells to glucose and insulin impairs this interaction, which relies on an intrinsically disordered region (D2 domain) within TSC22D4. Functionally, the interaction with TSC22D4 reduces basal phosphorylation of Akt and its downstream targets during starvation, thereby promoting insulin sensitivity. Genetic, liver-specific reconstitution experiments in mice demonstrate that the interaction between TSC22D4 and Akt1 improves glucose handling and insulin sensitivity. Overall, our findings postulate a model whereby TSC22D4 acts as an environmental sensor and interacts with Akt1 to regulate insulin signaling and glucose metabolism.}, } @article {pmid36259855, year = {2022}, author = {Peach, A and Blaise, B and Parker, J and Larson, R}, title = {Noninflammatory presentation of cutaneous breast cancer: a retrospective case series at a single academic institution with review of the literature.}, journal = {Dermatology online journal}, volume = {28}, number = {4}, pages = {}, doi = {10.5070/D328458515}, pmid = {36259855}, issn = {1087-2108}, mesh = {Humans ; Male ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; *Skin Neoplasms/diagnosis/pathology ; *Melanoma/pathology ; Hormones ; }, abstract = {Breast cancer with skin involvement is an uncommon clinical presentation of this malignancy. Breast cancer overall has a relatively high mortality rate and wide variety of presentations, making skin involvement by breast cancer a necessary consideration in the differential diagnosis for many types of breast lesions. A retrospective review of our own small academic dermatology outpatient clinic, between August 2006 and January 2020, found four cases of noninflammatory breast cancer with skin involvement diagnosed through biopsy by our dermatologists. This review was approved by the local Institutional Review Board. Of the four patients identified, three were female and one was male. One patient had prior history of invasive ductal carcinoma in remission before recurrence was diagnosed. Another patient had a history of melanoma in situ before diagnosis with breast cancer. Patients were treated with various combinations of surgery, radiation, and hormone therapy. These four cases are presented here in detail, which emphasize the role of the dermatologist in recognizing various cutaneous manifestations of noninflammatory breast cancer in order to make a timely diagnosis.}, } @article {pmid36258934, year = {2022}, author = {Salehiazar, S and Huang, H and Aghighi, M and Venegas, R}, title = {Lymphoepithelioma-Like Carcinoma of the Breast: A Case Report of a Rare Type of Invasive Carcinoma.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29231}, pmid = {36258934}, issn = {2168-8184}, abstract = {Lymphoepithelioma carcinoma (LELC) is an extremely rare type of mammary cancer. Based on the histology, it can be misdiagnosed with inflammatory lesions like mastitis and medullary carcinoma or other hematopoietic neoplasms like lymphoma in the breast. Since LELC has a good response to chemotherapy with a good prognosis, t is prognostically important to recognize LELC. We report a rare case of LELC in a 51-year-old pre-menopausal female with a left breast mass, diagnosed with invasive ductal carcinoma (IDC), LELC type, treated with mastectomy, followed by adjuvant chemotherapy and radiotherapy, with a disease-free interval of 10 months. Herein, we present the case with its clinical presentation, radiologic imaging, histopathological features, and immunohistochemistry (IHC) findings. The rarity of this type of breast tumor warrants studying the behavior of these uncommon tumors to avoid misdiagnosis and establish well-defined criteria for diagnosis.}, } @article {pmid36257189, year = {2022}, author = {Metz, L and Bowyer, T and Burnett, J and Dion, M and Eslinger, P and Friese, J and Doll, C and McIntyre, J and Schrom, B}, title = {Source Term Analysis of Xenon (STAX): An effort focused on differentiating man-made isotope production from nuclear explosions via stack monitoring.}, journal = {Journal of environmental radioactivity}, volume = {255}, number = {}, pages = {107037}, doi = {10.1016/j.jenvrad.2022.107037}, pmid = {36257189}, issn = {1879-1700}, abstract = {An overview of the hardware and software developed for the Source Term Analysis of Xenon (STAX) project is presented which includes the data collection from two stack monitoring systems installed at medical isotope production facilities, infrastructure to transfer data to a central repository, and methods for sharing data from the repository with users. STAX is an experiment to collect radioxenon emission data from industrial nuclear facilities with the goal of developing a better understanding of the global radioxenon background and the effect industrial radioxenon releases have on nuclear explosion monitoring. A final goal of this work is to utilize collected data along with atmospheric transport modeling to calculate the contribution of a peak or set of peaks detected by the International Monitoring System (IMS) to provide desired discriminating information to the International Data Centre (IDC) and National Data Centers (NDCs). Types of data received from the STAX equipment are shown and collected data was used for a case study to predict radioxenon concentrations at two IMS stations closest to the Institute for RadioElements (IRE) in Belgium. The initial evaluation of results indicate that the data is very valuable to the nuclear explosion monitoring community.}, } @article {pmid36249638, year = {2022}, author = {Adam, R and Herman, M and Hodges, L and Duong, TQ and Fineberg, S and Roknsharifi, S}, title = {Invasive Lobular Cancer Arising in a Surgical Scar From Lumpectomy for a Previous Invasive Ductal Cancer of the Breast.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e29054}, pmid = {36249638}, issn = {2168-8184}, abstract = {We describe a case of pathology-proven invasive lobular breast cancer (ILC) arising in a scar over 15 years after lumpectomy for previous invasive ductal carcinoma (IDC). The tumor was detected on screening mammography as a new focal asymmetry at the scar site and confirmed at diagnostic mammography. Ultrasound demonstrated an irregular, shadowing, hypoechoic mass at the scar site. Ultrasound-guided biopsy revealed poorly differentiated invasive lobular carcinoma. MRI and CT showed an irregular mass with pectoralis muscle invasion. Multimodality imaging findings are described. This is the first case to our knowledge reporting multimodality imaging findings of a breast cancer developing at the site of a surgical scar that is histologically different from the originally resected cancer.}, } @article {pmid36249118, year = {2022}, author = {Sabour Takanlou, L and Cecener, G and Sabour Takanlou, M and Ozturk Nazlioglu, H and Tezcan Unlu, H and Isik, O and Egeli, U and Tunca, B and Cubukcu, E and Tolunay, S and Gokgoz, MS}, title = {Correlation between Ubiquitin E3 Ligases (SIAHs) and Heat Shock Protein 90 in Breast Cancer Patients.}, journal = {Iranian journal of public health}, volume = {51}, number = {8}, pages = {1836-1846}, pmid = {36249118}, issn = {2251-6093}, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR, and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.

METHODS: The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85 invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018-2019, and its association with the clinicopathologic variables of patients was evaluated.

RESULTS: HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor tissue of patients with breast cancer. Moreover, this study observed a significant association between the high expression of SIAH2/HSP90 with ER status, high expression of HSP90 with Recurrence/Metastasis, and high expression of SIAH2 with Ki-67 proliferation index.

CONCLUSION: The HSP90 and SIAH2 expressions play a significant role in breast cancer development by combining the experimental and clinical data obtained from the literature.}, } @article {pmid36248759, year = {2022}, author = {Zengel, B and Çavdar, D and Özdemir, Ö and Taşlı, F and Karataş, M and Şimşek, C and Uslu, A}, title = {Gastrointestinal Tract Metastases of Invasive Lobular Carcinoma of the Breast: An Immunohistochemical Survey Algorithm.}, journal = {European journal of breast health}, volume = {18}, number = {4}, pages = {375-380}, pmid = {36248759}, issn = {2587-0831}, abstract = {Invasive lobular carcinoma (ILC) accounts for almost 15% of all breast carcinomas. The potential of ILC to metastasize to the gastointestinal system is significantly greater than that of invasive ductal carcinoma. Gastric metastasis occurred in the ninth year of the follow-up in a patient who was operated on the right breast due to ILC. The patient was investigated for simultaneous masses in the stomach and colon, and a random mass was found in her right breast.}, } @article {pmid36248758, year = {2022}, author = {Kelten Talu, C and Yeni Erdem, B and Arslan, E and Nazli, MA and Cakir, Y and Can Trabulus, D}, title = {The Clinicopathologic Features of 22 Cases With Primary Invasive Papillary Carcinoma of the Breast Identified in 1153 Cases With Invasive Breast Carcinoma: Single-Center Experience.}, journal = {European journal of breast health}, volume = {18}, number = {4}, pages = {360-370}, pmid = {36248758}, issn = {2587-0831}, abstract = {OBJECTIVE: Invasive papillary carcinoma (IPC) of the breast is an uncommon histologic subtype with limited data in the literature. The aim of this study was to increase the evidence base by presenting clinicopathological findings of cases diagnosed as IPC.

MATERIALS AND METHODS: Hematoxylin and eosin sections and immunostaining of surgical excision specimens diagnosed as invasive breast carcinoma were re-evaluated, retrospectively.

RESULTS: IPC was detected in 22 cases (1.9%), of which 7 (0.6%) had pure and 15 (1.3%) had mixed morphology. Histologic types accompanying IPC were: Invasive ductal carcinoma (IDC) (15/15); invasive micropapillary carcinoma (3/15); and pleomorphic lobular carcinoma (1/15). Patient ages ranged between 36 and 89 (median 56.5) and the tumor size from 8 to 70 mm (median 19 mm). The histologic grade was 3 in five cases, 2 in 13, and 1 in four cases. The nuclear grade was 3 in 10 cases and 2 in 12. The values of positivity for estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and Ki-67 index indicated Luminal B phenotype in 16 (72.7%), triple-negative in 5 (22.7%), and Luminal A in 1 case (4.6%). Ductal carcinoma in situ was noted in 19 cases (86.4%).

CONCLUSION: IPC was mostly detected as an accompanying carcinoma to IDC at postmenopausal ages and was mostly Luminal B phenotype with intermediate-to-high grade features.}, } @article {pmid36246806, year = {2022}, author = {Ren, Y and Zhang, J and Zhang, JD and Xu, JZ}, title = {Efficacy of digital breast tomosynthesis combined with magnetic resonance imaging in the diagnosis of early breast cancer.}, journal = {World journal of clinical cases}, volume = {10}, number = {28}, pages = {10042-10052}, pmid = {36246806}, issn = {2307-8960}, abstract = {BACKGROUND: The incidence and mortality rate of breast cancer in China rank 120[th] and 163[rd], worldwide, respectively. The incidence of breast cancer is on the rise; the risk increases with age but is slightly reduced after menopause. Early screening, diagnosis, and timely determination of the best treatment plan can ensure clinical efficacy and prognosis.

AIM: To evaluate the clinical value of magnetic resonance imaging (MRI) combined with digital breast tomosynthesis (DBT) in diagnosing early breast cancer and the effect of breast-conserving surgery by arc incision.

METHODS: This study was divided into two parts. Firstly, 110 patients with early breast cancer confirmed by pathological examination and 110 with benign breast diseases diagnosed simultaneously in Changzhi People's Hospital of Shanxi Province and Shanxi Dayi Hospital from May 2019 to September 2020 were included in the breast cancer group and the benign group, respectively. Both groups underwent DBT and MRI examination, and the pathological results were used as the gold standard to evaluate the effectiveness of the combined application of DBT and MRI in the diagnosis of early breast cancer. Secondly, according to the operation method, 110 patients with breast cancer were divided into either a breast-conserving group (69 patients) or a modified radical mastectomy group (41 patients). The surgical effect, cosmetic effect, and quality of life of the two groups were compared.

RESULTS: Among the 110 cases of breast cancer, 66 were of invasive ductal carcinoma (60.00%), and 22 were of ductal carcinoma in situ (20.00%). Among the 110 cases of benign breast tumors, 55 were of breast fibromas (50.00%), and 27 were of breast adenosis (24.55%). The sensitivity, specificity, and area under the curve (AUC) of DBT in the differential diagnosis of benign and malignant breast tumors were 73.64%, 84.55%, and 0.791, respectively. The sensitivity, specificity, and AUC of MRI in the differential diagnosis of benign and malignant breast tumors were 84.55%, 85.45%, and 0.850, respectively. The sensitivity, specificity, and AUC of DBT combined with MRI in the differential diagnosis of benign and malignant breast tumors were 97.27%, 93.64%, and 0.955, respectively. The blood loss, operation time and hospitalization time of the breast-conserving group were significantly lower than those of the modified radical treatment group, and the difference was statistically significant (P < 0.05). After 3 mo of observation, the breast cosmetic effect of the breast-conserving group was better than that of the modified radical group, and the difference was statistically significant (P < 0.05). Before surgery, the quality-of-life scores of the breast-conserving and modified radical mastectomy groups did not differ (P > 0.05). Three months after surgery, the quality-of-life scores in both groups were higher than those before surgery (P < 0.05), and the quality-of-life score of the breast-conserving group was higher than that of the modified radical group (P < 0.05). In the observation of tumor recurrence rate two years after the operation, four patients in the breast-conserving group and one in the modified radical treatment group had a postoperative recurrence. There was no significant difference in the recurrence rate between the two groups (χ [2] = 0.668, P = 0.414 > 0.05).

CONCLUSION: MRI combined with DBT in diagnosing early breast cancer can significantly improve the diagnostic efficacy compared with the two alone. Breast-conserving surgery leads to better cosmetic breast effects and reduces the impact of surgery on postoperative quality of life.}, } @article {pmid36246597, year = {2022}, author = {Zhao, Z and Jiang, N and Zhang, Y and Bai, Y and Liu, T and Li, T and Guo, H and Yang, R}, title = {Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {919829}, pmid = {36246597}, issn = {1664-8021}, abstract = {Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but the current therapeutic strategy based on chemotherapy and immune checkpoint inhibitor (ICI) therapy cannot meet the treatment needs, mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy and targeted drugs and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed the necroptosis landscape on therapy and prognosis in BLCA. We first divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analyses. Next, we constructed a novel necroptosis-related gene (NRG) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, and the accuracy of the NRG score was also verified by external datasets. In addition, a nomogram combining NRG score and several clinicopathological features was established to more accurately and conveniently predict the BLCA patient's survival. We also found that the NRG score was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD-1, TIGIT, and LAG3 of TME, and the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRG score has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME), and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICI therapy, and combination therapy.}, } @article {pmid36245246, year = {2022}, author = {Blawski, R and Toska, E}, title = {A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3668-3670}, pmid = {36245246}, issn = {1538-7445}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; R21 CA252530/CA/NCI NIH HHS/United States ; K22 CA245487/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Receptors, Estrogen/genetics/metabolism ; Retrospective Studies ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.}, } @article {pmid36243006, year = {2022}, author = {Sekar, R and Motzler, K and Kwon, Y and Novikoff, A and Jülg, J and Najafi, B and Wang, S and Warnke, AL and Seitz, S and Hass, D and Gancheva, S and Kahl, S and Yang, B and Finan, B and Schwarz, K and Okun, JG and Roden, M and Blüher, M and Müller, TD and Krahmer, N and Behrends, C and Plettenburg, O and Miaczynska, M and Herzig, S and Zeigerer, A}, title = {Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes.}, journal = {Cell metabolism}, volume = {34}, number = {11}, pages = {1824-1842.e9}, doi = {10.1016/j.cmet.2022.09.022}, pmid = {36243006}, issn = {1932-7420}, mesh = {Animals ; Mice ; *Diabetes Mellitus, Type 2/metabolism ; Endosomes/metabolism ; Glucagon/metabolism ; Glucose/metabolism ; Lipids ; Liver/metabolism ; Mammals/metabolism ; Mice, Inbred C57BL ; *Receptors, Glucagon/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; }, abstract = {During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.}, } @article {pmid36240525, year = {2022}, author = {Sandor, MF and Schwalbach, B and Hofmann, V and Istrate, SE and Schuller, Z and Ionescu, E and Heimann, S and Ragazzi, M and Lux, MP}, title = {Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {66}, number = {}, pages = {118-125}, pmid = {36240525}, issn = {1532-3080}, mesh = {Female ; Humans ; *Breast Neoplasms/diagnostic imaging/surgery/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery/pathology ; Lasers ; Margins of Excision ; Mastectomy, Segmental/methods ; Neoplasm Recurrence, Local/pathology ; Prospective Studies ; Reoperation ; Retrospective Studies ; }, abstract = {INTRODUCTION: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10-40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.

MATERIALS AND METHODS: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.

RESULTS: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.

CONCLUSION: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase-III-trial.}, } @article {pmid36239760, year = {2022}, author = {Oesterreich, S and Nasrazadani, A and Zou, J and Carleton, N and Onger, T and Wright, MD and Li, Y and Demanelis, K and Ramaswamy, B and Tseng, G and Lee, AV and Williams, N and Kruse, M}, title = {Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {114}, number = {11}, pages = {1511-1522}, pmid = {36239760}, issn = {1460-2105}, support = {NCI P30CA047904/NH/NIH HHS/United States ; NCI P30CA016058/CA/NCI NIH HHS/United States ; F30 CA264963/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; /KOMEN/Susan G. Komen/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy ; *Breast Neoplasms/drug therapy ; Receptors, Estrogen ; Retrospective Studies ; *Carcinoma, Lobular/diagnosis ; }, abstract = {BACKGROUND: There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC).

METHODS: The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values.

RESULTS: Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P < .001). Estrogen receptor-positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P < .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)-positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay.

CONCLUSIONS: This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.}, } @article {pmid36238916, year = {2022}, author = {Kim, YJ and Jung, HK and Kim, W}, title = {An Unusual Presentation of Extensive Ductal Carcinoma in Situ Accompanying Invasive Ductal Carcinoma on MRI: A Case Report.}, journal = {Journal of the Korean Society of Radiology}, volume = {83}, number = {4}, pages = {898-903}, pmid = {36238916}, issn = {2951-0805}, abstract = {The incidence of ductal carcinoma in situ has increased with the rise in screening mammography; currently, ductal carcinoma in situ constitutes 20%-25% of all breast cancers, and up to half of them may become invasive. Its early detection is critical in improving the cure rate. Moreover, MRI has higher sensitivity for its detection than mammography. Herein, we report an unusual case of ductal carcinoma in situ presenting as a continuous, serpentine, linear enhancement with regional distribution on MRI.}, } @article {pmid36238494, year = {2022}, author = {Zhao, W and Wu, T and Zhan, J and Dong, Z}, title = {Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {7153491}, pmid = {36238494}, issn = {1748-6718}, mesh = {Animals ; Biomarkers ; *Cardiomyopathy, Hypertrophic/genetics/metabolism ; Gene Regulatory Networks ; Mice ; *MicroRNAs ; Sequence Analysis, RNA ; }, abstract = {OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.

METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.

RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.

CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.}, } @article {pmid36237742, year = {2022}, author = {Makaranka, S and Frixou, M and Mustafa, A and Husain, E}, title = {Cutaneous Sebaceous Carcinoma Presenting as a Large Fungating Breast Tumour in Synchronicity With Primary Carcinomata of the Breasts.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28896}, pmid = {36237742}, issn = {2168-8184}, abstract = {Sebaceous carcinomas are rare malignant tumours which arise from sebaceous glands. They are subclassified into ocular and extraocular subtypes and most commonly occur in the head and neck region. Tumours below the neck occur infrequently, and most commonly resemble benign skin lesions such as pyogenic granulomata and molluscum contagiosum, or malignant skin tumours like basal and squamous cell carcinomas (SCCs). We report a case of an 86-year-old lady presenting with a fungating breast tumour which began as a "mole" and exhibited insidious growth over five years to reach a maximum size of 10 cm. An excision biopsy was performed by the breast surgery team and histopathological analysis revealed a sebaceous carcinoma arising from the skin adnexa. On subsequent follow up, the patient was found to have a 19 mm mass in the left breast and a 20 mm mass in the right breast, which was P5 and P3 on clinical palpation, respectively. Core biopsies of left and right breast lesions showed invasive lobular carcinoma and invasive ductal carcinoma with lobular features respectively; the patient was started on primary letrozole treatment. The patient also went on to have a 2 cm wide local excision of the sebaceous carcinoma scar which was excised down to the pectoralis fascia. This is a unique presentation of a sebaceous gland carcinoma presenting as a fungating breast tumour. These tumours have a high metastatic potential and local recurrence rate, and can co-exist with primary carcinoma of the breast.}, } @article {pmid36237483, year = {2022}, author = {Alsumai, TS and Alhazzaa, N and Alshamrani, A and Assiri, S and Alhefdhi, A}, title = {Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer.}, journal = {Breast cancer (Dove Medical Press)}, volume = {14}, number = {}, pages = {323-334}, pmid = {36237483}, issn = {1179-1314}, abstract = {PURPOSE: Sentinel lymph node (SLN) biopsy (SLNB) is the standard tool to stage the axilla of breast cancer patients. This study aimed to identify the predictors of positive SLNB in patients with clinically node-negative breast cancer.

PATIENTS AND METHODS: A retrospective, single-institution cohort of patients with early-stage breast cancer without clinically identifiable axillary lymphadenopathy was chosen from January 2010 to December 2018. Logistic regression was used to identify possible predictors of positive SLNB.

RESULTS: Four hundred and seventy patients were identified; their mean age was 50±11 years. Most patients had the following characteristics: invasive ductal carcinoma (n=382, 81.3%), unilateral tumor (n=461, 98.1%), unifocal disease (n=351, 74.7%), intermediate grade (n=276, 59.0%), and estrogen and progesterone receptor positivity with human epidermal growth factor receptor 2 negativity (n=305, 64.9%). The mean size of the breast mass was 2.3±1.5 cm. SLNB was positive in 128 (27.2%) cases. The mean number of SLNs was 2±1.2. Axillary lymph node dissection was performed in 109 patients. The mean number of lymph nodes removed was 15±6. In 66 (60.6%) of the 109 patients with metastatic axillary nodes, only the SLNs were found to be positive. The number of SLNs, tumor size, tumor grade, receptor status, prominent axillary lymph nodes, and lymphovascular invasion predicted positive SLNB (P = 0.01, 0.03, 0.03, and 0.04 and <0.001 and <0.001, respectively).

CONCLUSION: Our results suggest that a number of histopathological and radiological characteristics of breast cancer can predict SLNB positivity in clinically node-negative breast cancer patients.}, } @article {pmid36230503, year = {2022}, author = {Chang, YS and Chou, YP and Chung, CC and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Molecular Classification of Hepatocellular Carcinoma Using Wnt-Hippo Signaling Pathway-Related Genes.}, journal = {Cancers}, volume = {14}, number = {19}, pages = {}, pmid = {36230503}, issn = {2072-6694}, support = {DMR-111-131//China Medical University Hospital/ ; MOST-109-2320-B-039-052 and MOST-110-2321-B-039-002//Ministry of Science and Technology of Taiwan/ ; }, abstract = {In Taiwan, a combination of hepatitis B and C infection, economic boom-related food and alcohol overconsumption, and Chinese medicine prescriptions has led to a high rate of hepatocellular carcinoma (HCC). However, the causative factors and underlying tumor biology for this unique HCC environment have not been identified. Wnt and Hippo signaling pathways play an important regulatory role in HCC development, and their functions are generally considered as positive and negative regulators of cell proliferation, respectively. In this study, we characterized the molecular features of HCC using a newly developed classification system based on the expression of the Wnt-Hippo signaling pathway-related genes. RNA sequencing (RNA-Seq) was performed on liver tumor tissues from 100 patients with liver cancer. RNA-Seq data for 272 previously characterized Wnt-Hippo signaling pathway-related genes were used for hierarchical clustering. We analyzed the data in terms of prognostic value, transcriptome features, immune infiltration, and clinical characteristics, and compared the resulting subclasses with previously published classifications. Four subclasses of HCC (HCCW1-4) were identified. Subclass HCCW1 displayed the highest PCDHB4 expression. Subclass HCCW2 displayed lower Edmondson-Steiner grades (I and II) and CTNNB1 mutation frequencies. Subclass HCCW3 was associated with a good prognosis, the highest PCDHGB7 expression, high CD8+ naïve T cells abundance, and relatively low TP53 mutation rates. Subclass HCCW4 was associated with a poor prognosis, the highest PCDHB2 and PCDHB6 expression, a relatively high abundance of Th1 cells, NKT and class-switched memory B cells, relatively low enrichment of cDC, iDC, and CD4+ memory T cells, and high Edmondson-Steiner grades (III and IV). We also identified Wnt-Hippo signaling pathway-related genes that may influence immune cell infiltration. We developed a panel of 272 Wnt-Hippo signaling pathway-related genes to classify HCC into four groups based on Taiwanese HCC and The Cancer Genome Atlas Liver Hepatocellular Carcinoma datasets. This novel molecular classification system may aid the treatment of HCC.}, } @article {pmid36229464, year = {2022}, author = {Wong, HY and Sheng, Q and Hesterberg, AB and Croessmann, S and Rios, BL and Giri, K and Jackson, J and Miranda, AX and Watkins, E and Schaffer, KR and Donahue, M and Winkler, E and Penson, DF and Smith, JA and Herrell, SD and Luckenbaugh, AN and Barocas, DA and Kim, YJ and Graves, D and Giannico, GA and Rathmell, JC and Park, BH and Gordetsky, JB and Hurley, PJ}, title = {Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6036}, pmid = {36229464}, issn = {2041-1723}, support = {S10 OD023475/OD/NIH HHS/United States ; R01 CA194024/CA/NCI NIH HHS/United States ; S10 OD016355/OD/NIH HHS/United States ; T32 CA009582/CA/NCI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; R01 CA214494/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; R01 CA217987/CA/NCI NIH HHS/United States ; R01 CA211695/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Apolipoproteins E ; *Carcinoma, Intraductal, Noninfiltrating/genetics ; Extracellular Matrix Proteins ; Humans ; Ligands ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; RNA ; Receptors, Antigen, T-Cell ; Single-Cell Analysis ; Tumor Microenvironment/genetics ; }, abstract = {Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.}, } @article {pmid36223973, year = {2022}, author = {Singh, N and Singh, R and Decker, B and Robins, D and Vidal, G}, title = {Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.}, journal = {BMJ case reports}, volume = {15}, number = {10}, pages = {}, pmid = {36223973}, issn = {1757-790X}, mesh = {*Breast Neoplasms/genetics/pathology ; Carcinoma ; *Circulating Tumor DNA/genetics ; Female ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics ; Protein Kinase Inhibitors ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; }, abstract = {A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.}, } @article {pmid36220898, year = {2022}, author = {Batashvili, M and Sheaffer, R and Katz, M and Doron, Y and Kempler, N and Levy, DA}, title = {Behavioural reconsolidation interference not observed in a within-subjects design.}, journal = {NPJ science of learning}, volume = {7}, number = {1}, pages = {26}, pmid = {36220898}, issn = {2056-7936}, abstract = {Studies of reconsolidation interference posit that reactivation of a previously consolidated memory via a reminder brings it into an active, labile state, leaving it open for potential manipulation. If interfered with, this may disrupt the original memory trace. While evidence for pharmacological reconsolidation interference is widespread, it remains unclear whether behavioural interference using the presentation of competing information can engender it, especially in declarative memory. Almost all previous studies in this area have employed between-subjects designs, in which there are potential confounds, such as different retrieval strategies for the multiple conditions. In the current studies, within-subjects paradigms were applied to test the effects of reconsolidation interference on associative recognition and free recall. In Experiment 1, participants engaged in pair-associate learning of unrelated object pictures on Day 1, and after a reminder, interference, reminder + interference, or no manipulation (control) on Day 2, were tested on associative recognition of these pairs on Day 3. In Experiments 2 and 3, memoranda were short stories studied on Day 1. On Day 2, stories were assigned to either control, reminder, interference by alternative stories, or reminder + interference conditions. On Day 3 participants recalled the Day 1 stories, and answered yes/no recognition questions. Reminders improved subsequent memory, while interference was effective in reducing retrieval in differing degrees across the experiments. Importantly, the reminder + interference condition was no more effective in impairing retrieval than the interference-alone condition, contrary to the prediction of the behavioural reconsolidation-interference approach.}, } @article {pmid36216835, year = {2022}, author = {Tzachor, A and Richards, CE and Jeen, S}, title = {Transforming agrifood production systems and supply chains with digital twins.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {47}, pmid = {36216835}, issn = {2396-8370}, abstract = {Digital twins can transform agricultural production systems and supply chains, curbing greenhouse gas emissions, food waste and malnutrition. However, the potential of these advanced virtualization technologies is yet to be realized. Here, we consider the promise of digital twins across six typical agrifood supply chain steps and emphasize key implementation barriers.}, } @article {pmid36214134, year = {2022}, author = {Zweck, E and Scheiber, D and Schultheiss, HP and Kuss, O and Kelm, M and Roden, M and Westenfeld, R and Szendroedi, J}, title = {Impaired Myocardial Mitochondrial Respiration in Humans With Prediabetes: A Footprint of Prediabetic Cardiomyopathy.}, journal = {Circulation}, volume = {146}, number = {15}, pages = {1189-1191}, doi = {10.1161/CIRCULATIONAHA.122.058995}, pmid = {36214134}, issn = {1524-4539}, mesh = {Blood Glucose ; *Cardiomyopathies ; *Diabetes Mellitus, Type 2 ; Humans ; Mitochondria, Heart ; Myocardium ; *Prediabetic State ; Respiration ; }, } @article {pmid36213813, year = {2022}, author = {Akpoghor, OD and Eghonghon, AR and Osime, OC}, title = {Pattern of Emergency Presentation of Patients with Breast Cancer at the University of Benin Teaching Hospital.}, journal = {Journal of the West African College of Surgeons}, volume = {12}, number = {2}, pages = {70-74}, pmid = {36213813}, issn = {2276-6944}, abstract = {BACKGROUND: Breast cancer is the most common malignancy affecting women in Nigeria. Presentation is usually elective. However, some patients present as an emergency with complications of the disease and its treatment. This study aimed to capture the features of this population of patients with breast cancer presenting as an emergency.

MATERIALS AND METHODS: The study was a prospective cross-sectional study conducted between March 2021 and February 2022. All the patients with histologically diagnosed breast cancer presenting as an emergency were recruited into the study. Relevant information was retrieved and analysed.

RESULTS: Over the study period, 34 patients were recruited. They were all females and ages ranged between 27 and 74 years of age (mean: 45.56 ± 11.71 years), and the highest incidence was in the fifth decade of life. The first symptom in all patients was a breast lump, and the duration of disease ranged between 3 and 84 months (mean: 29.21 ± 22.38 months). The right breast was most commonly involved, and invasive ductal carcinoma (no specific type) was the commonest histologic type in 88.24% of cases. Over half of the patients seen had received no treatment after establishing the diagnosis of breast cancer. For those who received treatment, radiotherapy was the least accessed form of treatment. The most common symptoms were difficulty breathing and jaundice (29.41% each), and metastatic disease was the most common diagnosis. The duration of admission ranged between 1 and 35 days, and a mortality rate of 45.45% was recorded.

CONCLUSION: The most common indication for emergency presentation in patients with breast cancer was metastatic disease.}, } @article {pmid36213589, year = {2022}, author = {Paulson, MR and Maita, K and Avila, FR and Torres-Guzman, RA and Garcia, JP and Eldaly, A and Forte, AJ and Maniaci, MJ}, title = {Colectomy Complicated by High-Output Ileostomy Managed in a Virtual Hybrid Hospital-at-Home Program.}, journal = {Case reports in surgery}, volume = {2022}, number = {}, pages = {3177934}, pmid = {36213589}, issn = {2090-6900}, abstract = {Chronically ill patients with superimposed acute illness requiring hospitalization are more likely to develop an extended length of stay, hospital-acquired infections, and adverse events throughout their hospitalization. An excellent alternative to managing this population of patients in the traditional bricks-and-mortal (BAM) hospital is the hospital-at-home (HaH) model. The Advanced Care at Home (ACH) program is Mayo Clinic's HaH model that provides acute and postacute care to high-acuity patients in their homes rather than in the traditional hospital and skilled nursing facility. We report a case of postoperative care through the ACH program of a patient suffering from short gut syndrome, high-output ileostomy, and severe protein-calorie malnutrition in the setting of previously diagnosed triple-negative invasive ductal carcinoma (IDC) of the right breast complicated by lung and brain metastasis. The patient had multiple complications that required repeated scare escalations directed by a multidisciplinary virtual care. Despite these complications, the ACH model of care was able to keep the patient in the home setting the majority of the time, limiting BAM hospital days, and eliminating the need to use the emergency department for acute escalation for 3 months. The patient was able to recover during this time period and proceed to successful take-down of the ileostomy. This case highlights the benefits of the ACH program by offering high-acuity hospital-level care to severely ill patients in the comfort of their homes. Highly qualified providers paired with curated technology in the home allowed for prompt identification of patient decompensation and timely initiation of treatment while avoiding institutionalization.}, } @article {pmid36210658, year = {2022}, author = {Erdogan, O and Parlakgumus, A and Tas, ZA and Yener, K and Turan, U}, title = {Invasive and Non-invasive Ductal Carcinoma within Malignant Phyllodes Tumour with Axillary Lymph Node Metastases.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {S92-S94}, doi = {10.29271/jcpsp.2022.Supp2.S92}, pmid = {36210658}, issn = {1681-7168}, mesh = {Axilla/pathology ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Mastectomy ; *Phyllodes Tumor/pathology/surgery ; }, abstract = {Phyllodes tumours are uncommon breast neoplasms constituting 1-2% of breast malignancies. Metastasis is usually haematogenous, and axillary lymph node dissection is not routinely performed. A phyllodes tumour with concomitant invasive ductal carcinoma (IDC) is even rarer. When IDCor ductal carcinoma in-situ (DCIS) is detected, the management of the condition changes completely. We report a case of a 22-year female presenting with a mass in the right breast and palpable axillary lymph nodes. The pathological examination demonstrated a malignant phyllodes tumour with concomitant IDC and DCIS. The patient elected to have modified radical mastectomy, and the pathological examination showed metastasis in the axillary lymph nodes. The patient was administered appropriate therapy. At the last visit, she did not have the clinical signs of disease. This is the first youngest case of axillary lymph node metastases with both DCIS and IDC on pathological examination in malignant phyllodes tumour. Key Words: Malignant phyllodes, Invasive ductal carcinoma, Ductal carcinoma in-situ, Lymph node metastasis.}, } @article {pmid36208091, year = {2023}, author = {Lu, X and Ying, Y and Zhang, W and Li, R and Zhang, J}, title = {High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.}, journal = {Cell biology international}, volume = {47}, number = {1}, pages = {201-215}, doi = {10.1002/cbin.11925}, pmid = {36208091}, issn = {1095-8355}, support = {182102410095//Science and Technology Department of Henan Province/ ; 212102310466//Science and Technology Department of Henan Province/ ; 2019GGJS004//Education Department of Henan Province/ ; LHGJ20220473//Health Commission of Henan Province/ ; SBGJ202002119//Health Commission of Henan Province/ ; }, mesh = {Female ; Humans ; *Endometrial Neoplasms/diagnosis/pathology ; *MutS Homolog 2 Protein/genetics/metabolism ; Promoter Regions, Genetic ; *Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.}, } @article {pmid36206823, year = {2022}, author = {Maggi, G and Di Meglio, D and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {The impact of executive dysfunctions on Theory of Mind abilities in Parkinson's disease.}, journal = {Neuropsychologia}, volume = {176}, number = {}, pages = {108389}, doi = {10.1016/j.neuropsychologia.2022.108389}, pmid = {36206823}, issn = {1873-3514}, mesh = {Humans ; *Theory of Mind/physiology ; *Parkinson Disease/complications/psychology ; Neuropsychological Tests ; Executive Function/physiology ; *Cognitive Dysfunction ; }, abstract = {Theory of Mind (ToM) is the ability to infer and reason about others' mental states, a process impaired by Parkinson's disease (PD). ToM performance in PD seems to be strongly related to executive functioning but the exact nature of this relationship is still unclear. We aim to investigate the direct impact of several executive dysfunctions on ToM deficits (Affective and Cognitive ToM) in PD patients. Sixty-eight PD patients underwent neuropsychological tests evaluating executive control such as inhibition, cognitive flexibility, processing speed or working memory and Cognitive and Affective ToM. We divided participants into two groups based on their performance on executive tests: PD patients with poor executive functioning (PD-EF-) and those with preserved executive functioning (PD-EF+). To explore the direct impact of executive subdomains on ToM abilities, two mediation models were executed in the whole sample. We found that PD patients with poor executive functioning reported poorer scores on Affective and Cognitive ToM tasks than PD patients with preserved executive functions, controlling for age and education. Moreover, parallel mediation models, conducted in the whole sample, indicated that performance on phonological fluency mediated the relationships between educational level and both Affective and Cognitive ToM, controlling the effect of other executive tests. These findings further support the idea that executive functions are crucial in ToM processes. Particularly, phonological fluency, whose execution requires both verbal abilities and cognitive flexibility, mediated ToM performance controlling the effect of other executive functions. The identification of neuropsychological processes underpinning ToM abilities might represent a plausible target for cognitive training to strengthen ToM abilities in PD.}, } @article {pmid36203455, year = {2022}, author = {Zheng, Y and Bai, L and Sun, J and Zhu, L and Huang, R and Duan, S and Dong, F and Tang, Z and Li, Y}, title = {Diagnostic value of radiomics model based on gray-scale and contrast-enhanced ultrasound for inflammatory mass stage periductal mastitis/duct ectasia.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {981106}, pmid = {36203455}, issn = {2234-943X}, abstract = {OBJECTIVE: The present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitis/duct ectasia (IMSPDM/DE) and invasive ductal carcinoma (IDC).

METHODS: In this retrospective study, 254 patients (IMSPDM/DE: 129; IDC:125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDM/DE:40; IDC:40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses.

RESULTS: Three radiomics signatures were able to differentiate IMSPDM/DE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p<0.001), higher neutrophil count (p<0.001), lack of pausimenia (p=0.023) and GSCEUS radiomics features (p<0.001) were independent risk factors of IMSPDM/DE. The classification model that included the clinical factors and the GSCEUS radiomics signature outperformed the GSCEUS radiomics signature alone (the AUC values of the training and validation cohorts were 0.962 and 0.891, respectively). The nomogram was applied to the validation cohort, reaching optimal discrimination, with an AUC value of 0.891, a sensitivity of 0.888, and a specificity of 0.750.

CONCLUSIONS: The present study combined the clinical parameters with the GSCEUS radiomics signature and developed a nomogram. This GSCEUS radiomics-based classification model could be used to differentiate IMSPDM/DE from IDC in a non-invasive manner.}, } @article {pmid36202832, year = {2022}, author = {Shawi, RE and Kilanava, K and Sakr, S}, title = {An interpretable semi-supervised framework for patch-based classification of breast cancer.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {16734}, pmid = {36202832}, issn = {2045-2322}, mesh = {*Breast Neoplasms/diagnosis/pathology ; Cohort Studies ; Female ; Humans ; Neural Networks, Computer ; New Jersey ; Supervised Machine Learning ; }, abstract = {Developing effective invasive Ductal Carcinoma (IDC) detection methods remains a challenging problem for breast cancer diagnosis. Recently, there has been notable success in utilizing deep neural networks in various application domains; however, it is well-known that deep neural networks require a large amount of labelled training data to achieve high accuracy. Such amounts of manually labelled data are time-consuming and expensive, especially when domain expertise is required. To this end, we present a novel semi-supervised learning framework for IDC detection using small amounts of labelled training examples to take advantage of cheap available unlabeled data. To gain trust in the prediction of the framework, we explain the prediction globally. Our proposed framework consists of five main stages: data augmentation, feature selection, dividing co-training data labelling, deep neural network modelling, and the interpretability of neural network prediction. The data cohort used in this study contains digitized BCa histopathology slides from 162 women with IDC at the Hospital of the University of Pennsylvania and the Cancer Institute of New Jersey. To evaluate the effectiveness of the deep neural network model used by the proposed approach, we compare it to different state-of-the-art network architectures; AlexNet and a shallow VGG network trained only on the labelled data. The results show that the deep neural network used in our proposed approach outperforms the state-of-the-art techniques achieving balanced accuracy of 0.73 and F-measure of 0.843. In addition, we compare the performance of the proposed semi-supervised approach to state-of-the-art semi-supervised DCGAN technique and self-learning technique. The experimental evaluation shows that our framework outperforms both semi-supervised techniques and detects IDC with an accuracy of 85.75%, a balanced accuracy of 0.865, and an F-measure of 0.773 using only 10% labelled instances from the training dataset while the rest of the training dataset is treated as unlabeled.}, } @article {pmid36196411, year = {2022}, author = {Giap, F and O'steen, L and Liu, IC and Spiguel, LE and Shaw, CM and Morris, CG and Mailhot Vega, RB and Lightsey, JL and Bradley, JA and Mendenhall, NP and Okunieff, PG and Lockney, NA}, title = {Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {27}, number = {4}, pages = {666-676}, pmid = {36196411}, issn = {1507-1367}, abstract = {BACKGROUND: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).

MATERIALS AND METHODS: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.

RESULTS: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity.

CONCLUSIONS: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.}, } @article {pmid36196281, year = {2022}, author = {Culbert, M and Shock, L and Fabricius, MM and Nelson, N}, title = {Reverse Abdominoplasty for Reconstruction Following Oncologic Resection of Extensive Breast Disease.}, journal = {Cureus}, volume = {14}, number = {9}, pages = {e28664}, pmid = {36196281}, issn = {2168-8184}, abstract = {We present two cases of patients with extensive breast disease who underwent a reverse abdominoplasty for closure following resection: one of Paget's disease extending beyond the breast borders and another of a locally recurrent triple-negative invasive ductal carcinoma following mastectomy in a patient who previously had an ipsilateral thoracotomy. The reverse abdominoplasty flap is a reconstructive option not readily considered for closure following mastectomy. However, we believe that the reverse abdominoplasty flap should be considered when evaluating patients for anterior chest wall reconstruction because it is a simple and versatile coverage option.}, } @article {pmid36192585, year = {2022}, author = {Arakawa, T and Miyake, H and Nagai, H and Yoshioka, Y and Shibata, K and Takahashi, D and Yuasa, N and Sumi, H and Yoshikawa, K and Kiriyama, A and Fujino, M}, title = {Non-tumor forming and diffusely spreading invasive pancreatic cancer.}, journal = {Clinical journal of gastroenterology}, volume = {15}, number = {6}, pages = {1185-1192}, pmid = {36192585}, issn = {1865-7265}, mesh = {Male ; Humans ; Aged ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/surgery ; *Pancreatic Intraductal Neoplasms/pathology ; *Pancreatic Neoplasms/diagnostic imaging/surgery ; Pancreatectomy ; Pancreatic Ducts/diagnostic imaging/pathology ; }, abstract = {A 78-year-old man presented to our hospital with loss of appetite and epigastric discomfort. Computed tomography (CT) revealed dilation of the main pancreatic duct and three cystic lesions in the pancreatic neck, body, and tail. Endoscopic ultrasonography showed a mural nodule > 5 mm enhanced with Sonazoid in a cyst. Therefore, the patient was diagnosed with intra-ductal papillary mucinous neoplasm (IPMN) and underwent distal pancreatectomy. Macroscopic examination of the cut surface of the resected specimen showed no solid tumors in the pancreatic parenchyma. The histopathological diagnosis of the cysts was IPMN with low-grade dysplasia. Ten months after surgery, the serum carbohydrate antigen 19-9 level was elevated, and CT showed multiple peritoneal and pulmonary nodules, suggesting peritoneal dissemination and lung metastases. Since recurrence of pancreatic cancer was suspected, repeat histopathological examination of the resected specimen was performed, revealing small clusters of atypical epithelial cells diffusely spreading in the pancreatic tissue. The diagnosis was changed to invasive ductal carcinoma (pT2N1bM0, stage IIB). Invasive pancreatic cancer that does not form a solid mass, and shows diffuse spreading with small clusters is extremely rare. Imaging diagnosis and histopathological examination should be carefully performed in such cases.}, } @article {pmid36190529, year = {2022}, author = {van der Slot, MA and Seyrek, N and Kweldam, CF and den Bakker, MA and Busstra, MB and Gan, M and Klaver, S and Rietbergen, JBW and van Leenders, GJLH}, title = {Percentage Gleason pattern 4 and PI-RADS score predict upgrading in biopsy Grade Group 2 prostate cancer patients without cribriform pattern.}, journal = {World journal of urology}, volume = {40}, number = {11}, pages = {2723-2729}, pmid = {36190529}, issn = {1433-8726}, mesh = {Male ; Humans ; *Prostatic Neoplasms/surgery/pathology ; Magnetic Resonance Imaging ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; Biopsy ; }, abstract = {PURPOSE: To identify parameters to predict upgrading in biopsy Grade Group (GG) 2 prostate cancer patients without cribriform and intraductal carcinoma (CR/IDC) on biopsy.

METHODS: Preoperative biopsies from 657 men undergoing radical prostatectomy (RP) for prostate cancer were reviewed for GG, presence of CR/IDC, percentage Gleason pattern 4, and tumor length. In men with biopsy GG2 without CR/IDC (n = 196), clinicopathologic features were compared between those with GG1 or GG2 without CR/IDC on RP (GG ≤ 2-) and those with GG2 with CR/IDC or any GG > 2 (GG ≥ 2+). Logistic regression analysis was used to predict upgrading in the biopsy cohort.

RESULTS: In total 283 men had biopsy GG2 of whom 87 (30.7%) had CR/IDC and 196 (69.3%) did not. CR/IDC status in matched biopsy and RP specimens was concordant in 179 (63.3%) and discordant in 79 (27.9%) cases (sensitivity 45.1%; specificity 92.6%). Of 196 biopsy GG2 men without CR/IDC, 106 (54.1%) had GG ≥ 2+ on RP. Multivariable logistic regression analysis showed that age [odds ratio (OR): 1.85, 95% confidence interval (CI)1.09-3.20; p = 0.025], percentage Gleason pattern 4 (OR 1.54, 95% CI 1.17-2.07; p = 0.003), PI-RADS 5 lesion (OR 2.17, 95% CI 1.03-4.70; p = 0.045) and clinical stage T3 (OR 3.60; 95% CI 1.08-14.50; p = 0.049) were independent parameters to predict upgrading to GG ≥  2+ on RP in these men.

CONCLUSIONS: Age, clinical stage T3, percentage Gleason pattern 4 and presence of PI-RADS 5 lesions are independent predictors for upgrading in men with biopsy GG2 without CR/IDC. These findings allow for improved clinical decision-making on surveillance eligibility in intermediate-risk prostate cancer patients.}, } @article {pmid36189356, year = {2022}, author = {Saeed, U and Piracha, ZZ and Uppal, SR and Waheed, Y and Uppal, R}, title = {SARS-CoV-2 induced hepatic injuries and liver complications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {726263}, pmid = {36189356}, issn = {2235-2988}, mesh = {Aged ; *COVID-19/complications ; *Carcinoma, Hepatocellular ; *Gastrointestinal Diseases ; Humans ; Liver/pathology ; *Liver Neoplasms/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.

DISCUSSION: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.

CONCLUSION: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.}, } @article {pmid36182676, year = {2023}, author = {Sogunro, OA and Maini, M and Deldar, R and Maini, AS and Greige, N and Greenwalt, I and Wehner, P and De La Cruz, L and Son, JD}, title = {Prognostic Predictors of Mortality in Male Breast Cancer: Outcomes in an Urban Population.}, journal = {The Journal of surgical research}, volume = {281}, number = {}, pages = {192-199}, doi = {10.1016/j.jss.2022.08.035}, pmid = {36182676}, issn = {1095-8673}, mesh = {Humans ; Male ; Female ; *Breast Neoplasms, Male/pathology ; Prognosis ; Retrospective Studies ; Urban Population ; *Atrial Fibrillation ; *Breast Neoplasms ; *Kidney Failure, Chronic ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) accounts for 0.5% to 1% of all breast cancers diagnosed annually. The purpose of this study is to evaluate prognostic factors in MBC.

METHODS: We performed a retrospective chart review of patients with MBC between 2010 and 2021. Demographics, comorbidities, cancer characteristics, recurrence, and mortality were collected. Cox proportional hazards regression model was used to determine prognostic factors. A Kaplan-Meier curve was used to plot survival probabilities.

RESULTS: A total of 47 male patients were identified. The mean age at presentation was 64.1 y. Twenty eight (59.6%) patients were African American and 14 patients (29.8%) were Caucasian. Most patients had invasive ductal carcinoma (89.4%) and presented with T1 or T2 tumors (40.4% and 38.3%, respectively). Three patients (6.4%) had a recurrence and eight patients (17%) died. Using mortality as an end point, age (≥ 76.1 y) indicated a hazard ratio (HR) of 1.13 (P = 0.004), diabetes mellitus (HR = 5.45, P = 0.023), atrial fibrillation (HR = 8.0, P = 0.009), end-stage renal disease (HR 6.47, P = 0.023), Eastern Cooperative Oncology Group performance status of 3 (HR = 7.92, P = 0.024), poorly differentiated grade (HR = 7.21, P = 0.033), and metastatic disease (HR = 30.94, P = 0.015) had an increased risk of mortality. Overall survival at 3 y was 79.2%.

CONCLUSIONS: Advanced age, diabetes mellitus, atrial fibrillation, end-stage renal disease, Eastern Cooperative Oncology Group score of 3, poorly differentiated tumors, and metastatic disease are unfavorable prognostic factors in MBC. Compared to female breast cancer, MBC showed poorer overall survival.}, } @article {pmid36178915, year = {2022}, author = {Mussa, FM and Massawe, HP and Bhalloo, H and Moledina, S and Assenga, E}, title = {Magnitude and associated factors of anti-retroviral therapy adherence among children attending HIV care and treatment clinics in Dar es Salaam, Tanzania.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0275420}, pmid = {36178915}, issn = {1932-6203}, mesh = {Child ; Cross-Sectional Studies ; *HIV Infections/complications/drug therapy/epidemiology ; Humans ; Odds Ratio ; Surveys and Questionnaires ; Tanzania/epidemiology ; }, abstract = {INTRODUCTION: The HIV pandemic continues to contribute significantly towards childhood mortality and morbidity. The up-scaling of the Anti-retroviral therapy (ART) access has seen more children surviving and sanctions great effort be made on ensuring adherence. Adherence is a dynamic process that changes over time and is determined by variable factors. This necessitates the urgency to conduct studies to determine the potential factors affecting adherence in our setting and therefore achieve the 90-90-90 goal of sustainable viral suppression.

OBJECTIVES: To assess the magnitude and associated factors of ART adherence among children (1-14 years) attending HIV care and treatment clinics during the months of July to November 2018 in Dar es Salaam.

METHODS: A cross-sectional clinic-based study, conducted in three selected HIV care and treatment clinics in urban Dar es Salaam; Muhimbili National Hospital (MNH), Temeke Regional Referral Hospital (TRRH), Infectious Disease Centre- DarDar Paediatric Program (IDC-DPP) HIV clinics during the months of July to November 2018. HIV-infected children aged 1-14 years who had been on treatment for at least six months were consecutively enrolled until the sample size was achieved. A structured questionnaire was used for data collection. Four-day self-report, one-month self-recall report and missed clinic appointments were used to assess adherence. Frequencies and percentages were used to describe categorical data. The odds ratio was used to analyse the possible factors affecting ART adherence Logistic regression models were used to determine the factors associated with ART adherence. Analysis was conducted using SPSS version 20.0 and p-value <0.05 were considered statistically significant.

RESULTS: 333 participants were recruited. The overall good adherence (≥95%) was approximated to be 60% (CI-54.3-65.1) when subjected to all three measures. On multivariable logistic regression, factors associated with higher odds of poor adherence were found to be caregivers aged 17-25 years [AOR = 3.5, 95%CI-(1.5-8.4)], children having an inter-current illness [AOR = 10.8, 95%CI-(2.3-50.4)], disbelief in ART effectiveness [AOR = 5.495; 95%CI-(1.669-18.182)] and advanced clinical stage [AOR = 1.972; 95% CI-(1.119-3.484)]. The major reasons reported by caregivers for missing medications included forgetfulness (41%), high pill burden (21%), busy schedule (11%) and long waiting hours at the clinic (9%).

In the urban setting of Dar es Salaam, ART adherence among children was found to be relatively low when combined adherence measures were used. Factors associated with poor ART adherence found were younger aged caregivers, and child intercurrent illness, while factors conferring good adherence were belief in ART effectiveness and lower HIV clinical stage. More attention and support should be given to younger aged caregivers, children with concomitant illness and advanced HIV clinical stages. Educating caregivers on ART effectiveness may also aid in improving adherence.}, } @article {pmid36176414, year = {2022}, author = {Kawaguchi, S and Tamura, N and Tanaka, K and Kobayashi, Y and Sato, J and Kinowaki, K and Shiiba, M and Ishihara, M and Kawabata, H}, title = {Clinical prediction model based on 18F-FDG PET/CT plus contrast-enhanced MRI for axillary lymph node macrometastasis.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {989650}, pmid = {36176414}, issn = {2234-943X}, abstract = {PURPOSE: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are useful for detecting axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC); however, there is limited clinical evidence to demonstrate the effectiveness of the combination of PET/CT plus MRI. Further axillary surgery is not recommended against ALN micrometastasis (lesion ≤2 mm) seen in sentinel lymph nodes, especially for patients who received proper adjuvant therapy. We aimed to evaluate the efficacy of a prediction model based on PET/CT plus MRI for ALN macrometastasis (lesion >2 mm) and explore the possibility of risk stratification of patients using the preoperative PET/CT plus MRI and biopsy findings.

MATERIALS AND METHODS: We retrospectively investigated 361 female patients (370 axillae; mean age, 56 years ± 12 [standard deviation]) who underwent surgery for primary IDC at a single center between April 2017 and March 2020. We constructed a prediction model with logistic regression. Patients were divided into low-risk and high-risk groups using a simple integer risk score, and the false negative rate for ALN macrometastasis was calculated to assess the validity. Internal validation was also achieved using a 5-fold cross-validation.

RESULTS: The PET/CT plus MRI model included five predictor variables: maximum standardized uptake value of primary tumor and ALN, primary tumor size, ALN cortical thickness, and histological grade. In the derivation (296 axillae) and validation (74 axillae) cohorts, 54% and 61% of patients, respectively, were classified as low-risk, with a false-negative rate of 11%. Five-fold cross-validation yielded an accuracy of 0.875.

CONCLUSIONS: Our findings demonstrate the validity of the PET/CT plus MRI prediction model for ALN macrometastases. This model may aid the preoperative identification of low-risk patients for ALN macrometastasis and provide helpful information for PET/MRI interpretation.}, } @article {pmid36175695, year = {2022}, author = {Silva, FHS and Underwood, A and Almeida, CP and Ribeiro, TS and Souza-Fagundes, EM and Martins, AS and Eliezeck, M and Guatimosim, S and Andrade, LO and Rezende, L and Gomes, HW and Oliveira, CA and Rodrigues, RC and Borges, IT and Cassali, GD and Ferreira, E and Del Puerto, HL}, title = {Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {12}, pages = {212}, pmid = {36175695}, issn = {1559-131X}, support = {05/20160//PRPq UFMG/ ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Caspase 3 ; Female ; Fluorescein-5-isothiocyanate ; Humans ; RNA, Messenger ; SOXB1 Transcription Factors ; Tumor Suppressor Proteins ; Up-Regulation ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.

RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.

CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.}, } @article {pmid36172685, year = {2022}, author = {Alinezhadi, M and Makvandi, M and Kaydani, GA and Jazayeri, SN and Charostad, J and Talaeizadeh, AT and Angali, KA}, title = {Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {9}, pages = {3201-3207}, pmid = {36172685}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Alphapapillomavirus/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; Case-Control Studies ; DNA ; DNA, Viral/genetics ; Female ; *Fibroadenoma/genetics ; Formaldehyde ; Humans ; Middle Aged ; Papillomaviridae/genetics ; *Papillomavirus Infections ; Paraffin Embedding ; Young Adult ; }, abstract = {BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.

MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.

RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54±16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.

CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.}, } @article {pmid36172329, year = {2022}, author = {Zangouri, V and Niazkar, HR and Nasrollahi, H and Homapour, F and Ranjbar, A and Seyyedi, MS}, title = {Benign or premalignant? Idiopathic granulomatous mastitis later diagnosed as ductal carcinoma breast cancer: Case report and review of literature.}, journal = {Clinical case reports}, volume = {10}, number = {9}, pages = {e6323}, pmid = {36172329}, issn = {2050-0904}, abstract = {Idiopathic granulomatous mastitis (IGM) is a rare benign infectious disease of the breast, commonly presenting with a unilateral breast mass. Since GM's clinical presentation and imaging can be very similar to breast cancer, diagnosing GM can be challenging. So far, various reports have demonstrated the probable correlation and co-occurrence of granulomatous mastitis and breast cancer. This report presents a 38-year-old female with invasive ductal carcinoma, previously diagnosed as IGM.}, } @article {pmid36171873, year = {2022}, author = {Levy, DA}, title = {Optimizing the social utility of judicial punishment: An evolutionary biology and neuroscience perspective.}, journal = {Frontiers in human neuroscience}, volume = {16}, number = {}, pages = {967090}, pmid = {36171873}, issn = {1662-5161}, abstract = {Punishment as a response to impairment of individual or group welfare may be found not only among humans but also among a wide range of social animals. In some cases, acts of punishment serve to increase social cooperation among conspecifics. Such phenomena motivate the search for the biological foundations of punishment among humans. Of special interest are cases of pro-social punishment of individuals harming others. Behavioral studies have shown that in economic games people punish exploiters even at a cost to their own welfare. Additionally, neuroimaging studies have reported activity during the planning of such punishment in brain areas involved in the anticipation of reward. Such findings hint that there is an evolutionarily honed basic drive to punish social offenders. I argue that the transfer of punishment authority from the individual to the group requires that social offenders be punished as a public good, even if such punishment is not effective as retribution or deterrent. Furthermore, the social need for punishment of offenders has implications for alternatives to incarceration, publicity of punishment, and judicial structure.}, } @article {pmid36168611, year = {2022}, author = {Martin, TA and Choudhry, S and Holton, LH and Mylander, WC and Tafra, L and Liang, W and Jackson, RS}, title = {Outcomes of Margin Reexcision after Oncoplastic Breast Reduction.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {10}, number = {9}, pages = {e4509}, pmid = {36168611}, issn = {2169-7574}, abstract = {UNLABELLED: Tissue rearrangement after an oncoplastic breast reduction may complicate identification of margins during reexcision. Little is known about outcomes of reoperation in this setting.

METHODS: This is a single-institution, retrospective analysis of outcomes of margin reexcisions after lumpectomy with concurrent oncoplastic Wise-pattern reduction from 2015 to 2020. Outcomes assessed were the rate of successful breast conservation, in-breast recurrence, wound issues or complications, effect on cosmesis, and delay to onset of adjuvant therapy.

RESULTS: From 2015 to 2020, 649 patients underwent lumpectomy with oncoplastic Wise-pattern reduction. Forty-seven patients (7.2%) had greater than or equal to one positive margin(s); of these, 28 went directly to mastectomy, and 19 underwent margin reexcision. Residual disease was found in seven of 19 patients (37%) at reexcision. The rate of successful breast-conserving therapy was 95% with a mean follow-up of 31 months. There was one (5%) in-breast recurrence (invasive ductal carcinoma [IDC] occurring 30 months after the original operation); this patient had a mastectomy for treatment of her recurrence. The overall complication rate was 37%. Radiation was administered to 18 patients (95%), and two patients (11%) had delay of radiation past 6 weeks due to wound complications. Of the 14 patients with photographs available, 12 of 14 patients (86%) were blindly assessed to have equivalent or better cosmesis after margin reexcision (versus initial lumpectomy).

CONCLUSION: Margin reexcision after oncoplastic breast reduction with Wise-pattern is feasible and effective, and can be done without compromising the initial cosmetic results.}, } @article {pmid36168441, year = {2022}, author = {Wenger, D and Kurumety, S and Aydi, ZB}, title = {A case report: invasive ductal carcinoma in mosaic Li-Fraumeni syndrome.}, journal = {Journal of surgical case reports}, volume = {2022}, number = {9}, pages = {rjac408}, pmid = {36168441}, issn = {2042-8812}, abstract = {Li-Fraumeni syndrome (LFS) is a rare autosomal dominant condition caused by pathogenic variants in the TP53 tumor suppressor gene and characterized by a high lifetime risk of various cancers with a very early age of onset. We are presenting a 41-year-old woman with right invasive ductal cancer and no family history of cancers, diagnosed with mosaic LFS confirmed with blood and skin punch biopsy samples. She was treated with neoadjuvant chemotherapy, mastectomy and sentinel node biopsy with completion axillary dissection. Adjuvant radiation was not recommended due to increased risk of secondary cancers. She also elected to undergo risk reducing contralateral mastectomy. Further research is warranted to determine the appropriate clinical management and surveillance strategies in patients with mosaic LFS as whether individuals with mosaic LFS have differing cancer risks in comparison to classic germline LFS is unknown.}, } @article {pmid36168301, year = {2022}, author = {Amiri-Dashatan, N and Yekta, RF and Koushki, M and Arefi Oskouie, A and Esfahani, H and Taheri, S and Kazemian, E}, title = {Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.}, journal = {The International journal of biological markers}, volume = {37}, number = {4}, pages = {349-359}, doi = {10.1177/03936155221123343}, pmid = {36168301}, issn = {1724-6008}, mesh = {Humans ; Female ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Metabolomics/methods ; *Breast Neoplasms/pathology ; Case-Control Studies ; *Carcinoma, Ductal, Breast/metabolism ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2.

METHODS: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis.

RESULTS: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.

CONCLUSIONS: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.}, } @article {pmid36162357, year = {2022}, author = {Camarneiro, R and Ferreira, Á and Barros, M and Brito E Melo, M}, title = {Occult breast cancer presenting as axillary lymphadenopathy - Case Report.}, journal = {International journal of surgery case reports}, volume = {99}, number = {}, pages = {107677}, pmid = {36162357}, issn = {2210-2612}, abstract = {INTRODUCTION: Occult breast carcinoma (OBC) is a rare entity and therefore generates discussion regarding diagnosis, approach, and prognosis. This article aims to present a case of OBC and reviews some concepts discussed in the literature.

PRESENTATION OF CASE: 43-year-old woman with right axillary adenopathies, without further complaints, whose biopsy shows a lymph node metastasis from invasive ductal carcinoma of the breast. Breast study, breast RMI and FDG-PET did not identify the primary tumour. As decided by a multidisciplinary team, the patient underwent neoadjuvant chemotherapy, axillary surgery, breast radiotherapy and hormone therapy. Four years after surgery, the patient has no evidence of the primary tumour and no axillary recurrence.

DISCUSSION: OBC was described in 1907. Although the best therapeutic approach is widely discussed in the literature, it is consensual that as long as the existence of a primary tumour is excluded by breast MRI, the conservative approach (excision of axillary adenopathy and breast and axillary radiotherapy) is more advocated.

CONCLUSION: Breast cancer must be considered in the differential diagnosis of a patient with axillary lymphadenopathy. The conservative approach of OBC is the preferred since breast MRI does not identify any suspicious lumps.}, } @article {pmid36157240, year = {2022}, author = {Wang, L and Deng, X and Chen, Y and Zhao, Y and Li, Z}, title = {PRR15 Is a Novel Diagnostic and Prognostic Biomarker in Papillary Thyroid Cancer and Modulates the Tumor Microenvironment.}, journal = {Journal of oncology}, volume = {2022}, number = {}, pages = {3290479}, pmid = {36157240}, issn = {1687-8450}, abstract = {Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with PTC who are already in an advanced state have a dismal outlook. This study aimed to establish the diagnostic relevance of PRR15 expression in PTC patients as well as its levels in PTC samples and its connection with immune infiltrates. The TCGA and GEO datasets were combed through to obtain information on PTC patients. The "Limma" program was used to screen for differentially expressed mRNAs (DEMs), and the results were displayed using volcano plots and heat maps. The Wilcoxon test was used to examine the level of PRR15 expression in PTC patients in comparison with that of normal tissues. To study the connection between the immune infiltration level and PRR15 expression in PTC, the single-sample sequence set enrichment analysis (ssGSEA) from the R package was utilized. The expression of PRR15 was analyzed with RT-PCR in PTC cells and normal cells. In order to evaluate the diagnostic significance of PRR15 expression, ROC assays were carried out. Experiments using CCK-8 were carried out to investigate the impact that PRR15 knockdown could have on the proliferation of PTC cells. In this study, 17 overlapped DEMs between PTC specimens and normal specimens were identified, including MPPED2, IPCEF1, SLC4A4, PKHD1L1, DIO1, CRABP1, TPO, TFF3, SPX, TCEAL2, ZCCHC12, SYTL5, PRR15, CHI3L1, SERPINA1, GABRB2, and CITED1. Our attention focused on PRR15 which was highly expressed in PTC specimens as compared with nontumor specimens. PRR15 had an AUC value of 0.926 (95% CI 0.902-0.950) for PTC based on TCGA datasets. Pan-cancer assays suggested PRR15 as an oncogenic gene in many types of tumors. Moreover, we found that PRR15 expression was positively correlated with eosinophils, NK cells, NK CD56bright cells, IDC, macrophages, DC, mast cells, and Th1 cells. Further investigations with CCK-8 demonstrated that inhibiting PRR15 resulted in a decrease in the proliferation of PTC cells. Overall, PRR15 was confirmed to be a biomarker for PTC patients and a predictor of response to immunotherapy.}, } @article {pmid36156504, year = {2022}, author = {Gherlone, N and Sowa, P and Osipova, M and Walton, R}, title = {Acellular Dermal Matrix Mimicking a New Retroareolar Mass After Central Pillar Neonipple Reconstruction.}, journal = {Annals of plastic surgery}, volume = {89}, number = {5}, pages = {500-501}, doi = {10.1097/SAP.0000000000003270}, pmid = {36156504}, issn = {1536-3708}, mesh = {Female ; Humans ; Middle Aged ; *Acellular Dermis ; *Breast Neoplasms/surgery ; Mastectomy/methods ; *Mammaplasty/methods ; Nipples/surgery ; *Breast Implants ; *Breast Implantation/methods ; Retrospective Studies ; }, abstract = {Acellular dermal matrix (ADM) is an increasingly popular alloplastic cadaveric dermis used to enhance postmastectomy reconstruction. Acellular dermal matrix can be used as a nipple-shaped cylinder in central pillar nipple reconstruction to help maintain long-term projection. We report a unique presentation of ADM mimicking a retroareolar mass after central pillar neonipple reconstruction. A 49-year-old woman with a history of invasive ductal carcinoma underwent delayed nipple reconstruction after lumpectomy and oncoplastic closure using an inframammary V-Y advancement flap.The nipple reconstruction was performed using pretattoo and articulated tab flaps. A rolled tube of acellular dermal matrix was placed in the central aspect of the neonipple reconstruction for projection. At 4 months postoperative, a screening mammogram and ultrasound noted a new retroareolar mass classified as BIRADS 4 necessitating a breast biopsy. Biopsy revealed portions of fibrous connective tissue consistent with partially incorporated acellular dermal matrix allograft. There was no evidence of malignancy. To mitigate the risk of future radiographic or clinical misinterpretation of ADM in nipple reconstruction, the placement of radiopaque markers such as microclips on the ADM implant could be a useful adjunct. Radiologists and surgeons should include ADM artifact in their differential diagnosis of radiologic imaging when evaluating a new mass in the proximity of prior ADM placement in neonipple reconstruction of the breast.}, } @article {pmid36151122, year = {2022}, author = {Vitkin, E and Singh, A and Wise, J and Ben-Elazar, S and Yakhini, Z and Golberg, A}, title = {Nondestructive protein sampling with electroporation facilitates profiling of spatial differential protein expression in breast tumors in vivo.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15835}, pmid = {36151122}, issn = {2045-2322}, mesh = {Animals ; Electroporation ; Mice ; Neoplasm Proteins ; *Neoplasms/pathology ; Precision Medicine ; *Proteomics ; }, abstract = {Excision tissue biopsy, while central to cancer treatment and precision medicine, presents risks to the patient and does not provide a sufficiently broad and faithful representation of the heterogeneity of solid tumors. Here we introduce e-biopsy-a novel concept for molecular profiling of solid tumors using molecular sampling with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor by permeabilization of the cell membrane, it facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its non tissue destructive characteristics, e-biopsy enables probing the solid tumor multiple times in several distinct locations in the same procedure, thereby enabling the spatial profiling of tumor molecular heterogeneity.We demonstrate e-biopsy in vivo, using the 4T1 breast cancer model in mice to assess its performance, as well as the inferred spatial differential protein expression. In particular, we show that proteomic profiles obtained via e-biopsy in vivo distinguish the tumors from healthy breast tissue and reflect spatial tumor differential protein expression. E-biopsy provides a completely new molecular sampling modality for solid tumors molecular cartography, providing information that potentially enables more rapid and sensitive detection at lesser risk, as well as more precise personalized medicine.}, } @article {pmid36143823, year = {2022}, author = {Nanev, V and Naneva, S and Yordanov, A and Strashilov, S and Konsoulova, A and Vasileva-Slaveva, M and Betova, T and Ivanov, I}, title = {Lymphoepithelioma-like Carcinoma of the Breast Synchronous with a High-Grade Invasive Ductal Carcinoma and Ductal Carcinoma in Situ in a Different Quadrant of the Same Breast: A Case Report.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {9}, pages = {}, pmid = {36143823}, issn = {1648-9144}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Middle Aged ; }, abstract = {Lymphoepithelioma-like breast carcinoma (LELC) is a rare type of malignant breast tumor that is not included in the current edition of the World Health Organization (WHO) classification of breast tumors. Currently, there are no clearly defined therapeutic strategies, and the general information on breast LELC is based on sporadic clinical cases described in the medical literature. We present a clinical case that describes a 49-year-old woman with a tumor formation in the right breast, histologically verified as LELC, together with a non-palpable, synchronous high-grade invasive ductal carcinoma and ductal carcinoma in situ Grade 2 (DCIS G2) in a different quadrant of the same breast. To our knowledge, this is the first case described in the literature that combines a LELC with a synchronous carcinoma in the same breast.}, } @article {pmid36131945, year = {2022}, author = {Ramdass, MJ and Gonzales, J and Maharaj, D and Simeon, D and Barrow, S}, title = {Breast Carcinoma Receptor Expression in a Caribbean Population.}, journal = {Surgery journal (New York, N.Y.)}, volume = {8}, number = {3}, pages = {e262-e265}, pmid = {36131945}, issn = {2378-5128}, abstract = {Trinidad and Tobago are islands in the Southern Caribbean with a unique mix of races within the population consisting of East Indian (EI) (37.6%), Afro-Caribbean (AC) (36.3%), mixed (24.2%), and Caucasian, Chinese, Lebanese, Syrian, Amerindian, and Spanish groups accounting for 1.9%. It makes it suitable for a comparison of breast carcinoma receptor expression within a fixed environment. This study included 257 women with an age range of 28 to 93 years (mean = 57.2, standard deviation = 15.0), peak age group of 51 to 60 consisting of 105 EI, 119 AC, and 33 mixed descent. Invasive ductal carcinoma accounted for 88%, invasive lobular 9.7%, and ductal carcinoma in situ 2.3%. The triple-negative rates were 24.8, 33.6, and 30.3% for EI, AC, and mixed races, respectively, with the Pearson's chi-square test revealing statistical significance for the AC versus EI (p < 0.001); AC versus mixed (p < 0.001); and EI versus mixed (p = 0.014) groups. The overall estrogen (ER), progesterone (PR), and human epidermal growth receptor (HER) expression negative rates were 52, 64, and 79%, respectively. Chi-square test of the following combinations: ER +/PR +/HER + ; ER +/PR +/HER - ; ER -/PR -/HER + ; ER +/PR -/HER + ; ER +/PR -/HER - ; ER -/PR +/HER + ; ER -/PR +/HER- revealed no statistical differences (p = 0.689).}, } @article {pmid36131807, year = {2022}, author = {Sapon-Cousineau, S and Moldoveanu, D and Charpentier, D and Gagnon, A and Patocskai, É}, title = {Locally advanced breast cancer arising in the axilla.}, journal = {Journal of surgical case reports}, volume = {2022}, number = {9}, pages = {rjac425}, pmid = {36131807}, issn = {2042-8812}, abstract = {Locally advanced breast cancer arising from ectopic axillary breast tissue is an unusual presentation of this malignancy. The work-up and treatment approach pose some unique challenges. We present the case of a 37-year-old female presenting with a left axillary lesion with skin involvement. Radiological studies and biopsy demonstrated an underlying axillary mass compatible with a triple-positive invasive ductal carcinoma of the breast. Following neoadjuvant therapy, the patient underwent nipple-sparing mastectomy with wide local excision of the involved axillary skin and axillary lymph node dissection. Ectopic locally advanced breast cancer can be treated similarly to its orthotopic counterpart, favoring a neoadjuvant therapy approach followed by surgical excision. Special considerations include the local anatomy of the tumor, the extent of surgery and reconstructive options.}, } @article {pmid36128357, year = {2022}, author = {Miyazaki, Y and Shimizu, J and Kubo, Y and Tabata, N and Aso, T}, title = {Quantitative classification of invasive and noninvasive breast cancer using dynamic magnetic resonance imaging of the mammary gland.}, journal = {Journal of clinical imaging science}, volume = {12}, number = {}, pages = {45}, pmid = {36128357}, issn = {2156-7514}, abstract = {OBJECTIVES: Breast cancers are classified as invasive or noninvasive based on histopathological findings. Although time-intensity curve (TIC) analysis using magnetic resonance imaging (MRI) can differentiate benign from malignant disease, its diagnostic ability to quantitatively distinguish between invasive and noninvasive breast cancers has not been determined. In this study, we evaluated the ability of TIC analysis of dynamic MRI data (MRI-TIC) to distinguish between invasive and noninvasive breast cancers.

MATERIAL AND METHODS: We collected and analyzed data for 429 cases of epithelial invasive and noninvasive breast carcinomas. TIC features were extracted in washout areas suggestive of malignancy.

RESULTS: The graph determining the positive diagnosis rate for invasive and noninvasive cases revealed that the cut-off θi/ni value was 21.6° (invasive: θw > 21.6°, noninvasive: θw ≤ 21.6°). Tissues were classified as invasive or noninvasive using this cut-off value, and each result was compared with the histopathological diagnosis. Using this method, the accuracy of tissue classification by MRI-TIC was 88.6% (380/429), which was higher than that using ultrasound (73.4%, 315/429).

CONCLUSION: MRI-TIC is effective for the classification of invasive vs. noninvasive breast cancer.}, } @article {pmid36120242, year = {2022}, author = {Ali, S and Rathore, Z and Rafique, Z and Chughtai, AS and Atiq, A}, title = {Expression of SOX10 in Triple-Negative Breast Carcinoma in Pakistan.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27938}, pmid = {36120242}, issn = {2168-8184}, abstract = {Background The term triple-negative breast cancer (TNBC) refers to a particular class of aggressive, poorly differentiated neoplasms that show the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) antibodies. SOX10 (SRY-related HMG-box 10) is a nuclear transcription factor that is commonly used to identify cancers of neural origin, but it has recently been linked to TNBC. The purpose of this study is to determine SOX10 expression in TNBC, its association with tumor grade for molecular categorization, and to determine the diagnostic significance of SOX10 in TNBC at the metastatic site in the case of an unknown primary. Methodology SOX10 was used to stain a tissue microarray of 100 patients. According to the tumor grade, SOX10 staining was classified as negative (<1%), patchy (1-10%), focal (10-70%), and diffuse (70-100%). SPSS version 22 (IBM Corp., Armonk, NY, USA) software was used to conduct the statistical analysis. Results The expression of SOX10 regarding positivity and intensity was higher in high-grade tumors than in intermediate-grade tumors (p = 0.001 and p = 0.007, respectively). Conclusions SOX10 is a reliable novel marker for the diagnosis of TNBC and has diagnostic utility in the unknown primary at the metastatic site.}, } @article {pmid36110985, year = {2022}, author = {}, title = {Erratum: Skin eruption involving bilateral breasts following radiation therapy for invasive ductal carcinoma of the left breast: Erratum.}, journal = {International journal of women's dermatology}, volume = {8}, number = {3}, pages = {e052}, pmid = {36110985}, issn = {2352-6475}, abstract = {[This corrects the article DOI: 10.1097/JW9.0000000000000016.].}, } @article {pmid36109587, year = {2022}, author = {Sobhani, F and Muralidhar, S and Hamidinekoo, A and Hall, AH and King, LM and Marks, JR and Maley, C and Horlings, HM and Hwang, ES and Yuan, Y}, title = {Spatial interplay of tissue hypoxia and T-cell regulation in ductal carcinoma in situ.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {105}, pmid = {36109587}, issn = {2374-4677}, abstract = {Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.}, } @article {pmid36107313, year = {2022}, author = {Walth-Hummel, AA and Herzig, S and Rohm, M}, title = {Nuclear Receptors in Energy Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1390}, number = {}, pages = {61-82}, pmid = {36107313}, issn = {0065-2598}, mesh = {Adipose Tissue/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Energy Metabolism/physiology ; Humans ; *Metabolic Diseases/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.}, } @article {pmid36101863, year = {2022}, author = {Yu, T and Cheng, W and Wang, T and Chen, Z and Ding, Y and Feng, J and Duan, Y and Hu, A and Li, M and Zhang, H and Li, Y and Ma, F and Guo, B}, title = {Survival Outcomes of Breast-Conserving Therapy versus Mastectomy in Early-Stage Breast Cancer, Including Centrally Located Breast Cancer: A SEER-Based Study.}, journal = {The breast journal}, volume = {2022}, number = {}, pages = {5325556}, pmid = {36101863}, issn = {1524-4741}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Mastectomy, Segmental ; }, abstract = {PURPOSE: This study aims to analyze the survival outcomes of breast cancer (BC) patients, especially centrally located breast cancer (CLBC) patients undergoing breast-conserving therapy (BCT) or mastectomy.

METHODS: Surveillance, epidemiology, and end results (SEER) data of patients with T1-T2 invasive ductal or lobular breast cancer receiving BCT or mastectomy were reviewed. We used X-tile software to convert continuous variables to categorical variables. Chi-square tests were utilized to compare baseline information. The multivariate logistic regression model was performed to evaluate the relationship between predictive variables and treatment choice. Survival outcomes were visualized by Kaplan-Meier curves and cumulative incidence function curves and compared using multivariate analyses, including the Cox proportional hazards model and competing risks model. Propensity score matching was performed to alleviate the effects of baseline differences on survival outcomes.

RESULT: A total of 180,495 patients were enrolled in this study. The breast preservation rates fluctuated around 60% from 2000 to 2015. Clinical features including invasive ductal carcinoma (IDC), lower histologic grade, smaller tumor size, fewer lymph node metastases, positive ER and PR status, and chemotherapy use were independently correlated with BCT in both BC and CLBC cohorts. In all the classic Cox models and competing risks models, BCT was an independent favorable prognostic factor for BC, including CLBC patients in most subgroups. In addition, despite the low breast-conserving rate compared with tumors located in the other areas, CLBC did not impair the prognosis of BCT patients.

CONCLUSION: BCT is optional and preferable for most early-stage BC, including CLBC patients.}, } @article {pmid36098873, year = {2022}, author = {Hiraoka, E and Masumoto, N and Furukawa, T and Kuraoka, N and Nagamine, I and Kido, A and Sentani, K and Ootagaki, S}, title = {Follicular lymphoma without lymphadenopathy incidentally diagnosed by sentinel lymph node biopsy during breast cancer surgery: a case report.}, journal = {Surgical case reports}, volume = {8}, number = {1}, pages = {167}, pmid = {36098873}, issn = {2198-7793}, abstract = {BACKGROUND: Concurrent breast cancer and malignant lymphoma is a rare phenomenon. This report describes malignant lymphoma that was incidentally diagnosed from a sentinel lymph node biopsy (SLNB) during breast cancer surgery.

CASE PRESENTATION: A 73-year-old woman with a history of ovarian cancer and diabetes presented with right focal asymmetric density on a mammogram acquired during routine breast cancer screening. Ultrasonography (US) and magnetic resonance imaging (MRI) showed a 13.5-mm tumor in the upper lateral region of the right breast. A US-guided Mammotome biopsy revealed invasive ductal carcinoma of the right breast. Preoperative assessments including positron emission tomography-computerized tomography, found no evidence of axillary lymphadenopathy or distant metastasis. Because the breast cancer was stage I, the patient underwent a right mastectomy and a sentinel lymph node biopsy (SLNB) at our hospital. Pathological assessment of the biopsy revealed follicular lymphoma (FL), but no metastatic breast cancer. The patient was referred to hematology to stage the FL. Bone marrow findings were negative and stage I FL was diagnosed. After the mastectomy, she was monitored and given adjuvant therapy with an aromatase inhibitor.

CONCLUSIONS: Follicular lymphoma was incidentally diagnosed from an SLNB obtained to determine the dissemination of early-stage breast cancer. Collaboration with hematologists is important to determine optimal treatment plans for such patients regardless of the rarity of such events.}, } @article {pmid36098816, year = {2023}, author = {Patil, A and Swerdlow, SH and Lossos, IS and Chapman, JR}, title = {Atypical follicular hyperplasia with light chain-restricted germinal centers after COVID-19 booster: a diagnostic pitfall.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {482}, number = {5}, pages = {905-910}, pmid = {36098816}, issn = {1432-2307}, mesh = {Humans ; Female ; COVID-19 Vaccines/adverse effects ; Hyperplasia/pathology ; *COVID-19/pathology ; Neoplasm Recurrence, Local/pathology ; *Precancerous Conditions/pathology ; Germinal Center/pathology ; *Lymphoma, Follicular/pathology ; *Lymphadenopathy/pathology ; *Breast Neoplasms/pathology ; COVID-19 Testing ; }, abstract = {There has been a surge in COVID-19 vaccine-associated lymphadenopathy (LAD), including after the booster dose of vaccine. This can create diagnostic dilemmas in oncology patients as the relatively sudden LAD can mimic metastasis or cancer recurrence, at a risk of leading to additional but unnecessary anti-neoplastic therapy. Here we report the histopathologic features in a case of persistent LAD occurring in a patient with history of breast invasive ductal carcinoma which followed a COVID-19 vaccine booster. A needle core and then excisional biopsy showed atypical follicular hyperplasia with features that histologically and phenotypically could mimic follicular lymphoma, but the findings were ultimately interpreted to be reactive in nature and related temporally to COVID-19 vaccine. To our knowledge, this is the first case of an atypical lymphoproliferative lesion with features potentially mimicking lymphoma associated with COVID-19 vaccine.}, } @article {pmid36097900, year = {2022}, author = {Gao, BB and Zheng, Q and Yu, L and Luo, DJ and Nie, X and Xu, X}, title = {[Clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {51}, number = {9}, pages = {843-849}, doi = {10.3760/cma.j.cn112151-20220430-00356}, pmid = {36097900}, issn = {0529-5807}, mesh = {*Carcinoma, Ductal ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Receptor, ErbB-2/metabolism ; }, abstract = {Objective: To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma (MSCC) of the breast. Methods: A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from January 2010 to December 2021 were reviewed. The clinical information (including the follow-up data of HER2 positive patients) and pathological features were collected and analyzed. Results: All of the patients were female. Among the 47 cases, 25 were pure squamous cell carcinoma (PSCC) and 22 were mixed metaplastic carcinoma with squamous cell component (MMSC). The median age of the patients was 54 years (range, 29-84 years). The maximum diameter of the mass ranged from 0.8 to 10.0 cm, with a mean value of 3.3 cm, 85.7% (24/28) of the cases were smaller than 5 cm, and only 4 cases were larger than or equal to 5 cm. 89.5% of the MMSC presented with a solid mass. Cystic changes were more commonly found in the PSCC group (50%, P<0.05) than the MMSC group. 36.7% (11/30) of the patients had lymph node metastasis at the time of diagnosis. The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63, p40 and CK5/6. 55.3% (26/47) of the cases showed triple-negative phenotype. Among the 7 HER2-positive patients, 6 were MMSC group, which had a significantly higher rate of HER2-positivity than that in the PSCC group (1 case). In 1 MMSC case, immunohistochemistry showed HER2 2+in the invasive ductal carcinoma component and HER2 negativity (0) in the squamous cell carcinoma component, but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component. Six HER2-positive MSCC patients received anti-HER2-targeted therapy, including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery. One patient achieved pathological complete remission, while the other achieved partial remission (the residual tumors were squamous cell carcinoma components). After 9-26 months of follow-up, four patients had no disease progression, two patients developed pulmonary metastases, and one patient showed local recurrence. Conclusions: MSCC is a group of heterogeneous diseases. PSCC and MMSC may be two different entities. Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component. Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy, but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.}, } @article {pmid36097899, year = {2022}, author = {Pan, XY and Wu, JK and Lang, ZQ and Qu, L and Jiang, L}, title = {[The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {51}, number = {9}, pages = {838-842}, doi = {10.3760/cma.j.cn112151-20220428-00339}, pmid = {36097899}, issn = {0529-5807}, mesh = {Antigens, CD34 ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Cell Adhesion Molecules ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; *Neuroblastoma ; }, abstract = {Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.}, } @article {pmid36096439, year = {2022}, author = {Li, H and Wang, S and Zeng, Q and Chen, C and Lv, X and Ma, M and Su, H and Ma, B and Chen, C and Fang, J}, title = {Serum Raman spectroscopy combined with multiple classification models for rapid diagnosis of breast cancer.}, journal = {Photodiagnosis and photodynamic therapy}, volume = {40}, number = {}, pages = {103115}, doi = {10.1016/j.pdpdt.2022.103115}, pmid = {36096439}, issn = {1873-1597}, mesh = {Humans ; Female ; Spectrum Analysis, Raman/methods ; *Breast Neoplasms/diagnosis ; Reproducibility of Results ; *Photochemotherapy/methods ; Discriminant Analysis ; Support Vector Machine ; Principal Component Analysis ; Algorithms ; }, abstract = {Breast cancer is a malignant tumor with the highest incidence rate in women. Current diagnostic methods are time-consuming, costly, and dependent on physician experience. In this study, we used serum Raman spectroscopy combined with multiple classification algorithms to implement an auxiliary diagnosis method for breast cancer, which will help in the early diagnosis of breast cancer patients. We analyzed the serum Raman spectra of 171 invasive ductal carcinoma (IDC) and 100 healthy volunteers; The analysis showed differences in nucleic acids, carotenoids, amino acids, and lipid concentrations in their blood. These differences provide a theoretical basis for this experiment. First, we used adaptive iteratively reweighted penalized least squares (airPLS) and Savitzky-Golay (SG) for baseline correction and smoothing denoising to remove the effect of noise on the experiment. Then, the Principal component analysis (PCA) algorithm was used to extract features. Finally, we built four classification models: support vector machine (SVM), decision tree (DT), linear discriminant analysis (LDA), and Neural Network Language Model (NNLM). The LDA, SVM, and NNLM achieve 100% accuracy. As supplementary, we added the classification experiment of the raw data. By comparing the experimental results of the two groups, We concluded that the NNLM was the best model. The results show the reliability of the combination of serum Raman spectroscopy and classification models under large sample conditions.}, } @article {pmid36093543, year = {2022}, author = {Li, C and Qian, B}, title = {Male triple negative axillary accessory breast cancer-a case report.}, journal = {Translational cancer research}, volume = {11}, number = {8}, pages = {2926-2930}, pmid = {36093543}, issn = {2219-6803}, abstract = {BACKGROUND: Breast cancer is the most common malignancy among women worldwide. In men, cases of breast cancer are few and account for less than 1% of all cases of breast cancer. Majority of male breast cancer is hormone receptor-positive. The incidence of male breast cancer derived from axillary accessory breast is very low. Here we report a case of male triple negative axillary accessory breast cancer.

CASE DESCRIPTION: We present a case of male triple negative axillary accessory breast cancer in a 67-year-old man, which progressively increased in size through a period of 1 year. Ultrasound examination showed a 31 mm × 17 mm mass in the right axillary tail region with some accessory breast tissue around. We performed right accessory breast resection and right axillary lymph nodes dissection. Postoperative pathological analysis revealed right accessory breast invasive ductal carcinoma with apocrine metaplasia. The tumor size was 3.5 cm × 3.3 cm. In addition, 5 metastatic lymph nodes were seen in 27 axillary lymph nodes. Immunohistochemistry showed estrogen-receptor (ER) (-), progesterone-receptor (PR) (-), human epidermal growth factor receptor 2 (HER2) (2+). Fluorescence in situ hybridization (FISH) test obtained a negative result. The patient was treated with adjuvant chemotherapy and radiotherapy. Until now, no obvious signs of recurrence or metastasis have been observed during regular follow-ups.

CONCLUSIONS: Male triple negative axillary accessory breast cancer is rare. Treatment of male triple negative axillary accessory breast cancer is similar to that of women. Most patients undergo surgery and adjuvant chemotherapy.}, } @article {pmid36093343, year = {2022}, author = {Choi, JI and Prabhu, K and Hartsell, WF and DeWees, T and Sinesi, C and Vargas, C and Benda, RK and Cahlon, O and Chang, AL}, title = {Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial.}, journal = {Clinical and translational radiation oncology}, volume = {37}, number = {}, pages = {71-77}, pmid = {36093343}, issn = {2405-6308}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI.

METHODS AND MATERIALS: This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL).

RESULTS: Thirty-eight evaluable patients enrolled between 2/2013-11/2016. Median age was 67 years (range 50-79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12-62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively.

CONCLUSION: At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.}, } @article {pmid36089720, year = {2022}, author = {Aker, FV and Ekren, E and Dogan, M and Gurleyik, G and Tanrikulu, E and Oven, BB}, title = {Clinicopathological Features and Prognosis of Invasive Micropapillary Carcinoma Compared to Invasive Ductal Carcinoma-NOS: Worse or Better?.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {9}, pages = {1196-1201}, doi = {10.29271/jcpsp.2022.09.1196}, pmid = {36089720}, issn = {1681-7168}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Papillary/pathology ; Female ; Humans ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate whether there are differences in invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma-NOS (IDC-NOS) according to the clinicopathological features and prognosis including molecular subtypes.

STUDY DESIGN: Descriptive study.

PLACE AND DURATION OF STUDY: Department of Pathology, University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, from 2003 to 2016.

METHODOLOGY: Operated breast cancer cases (58 IMPC + 326 IDC-NOS), with long-term follow-up findings (cases followed up until 2020), were reviewed. The cases, whose other component was only IDC-NOS, were included in the mixed IMPC group. The clinical features, including clinical presentation, treatments, and follow-up information were obtained from the patient clinical database. The IMPC cases included in the study were re-examined, and micropapillary tumour components were confirmed based on the criteria set by the World Health Organisation (WHO). The clinicopathological findings, recurrence, and survival data of both groups were compared. In addition, IDC-NOS was divided into the molecular subgroups and compared with IMPC cases in terms of 5-year overall survival (OS).

RESULTS: There was no significant difference between the two groups for the distribution of molecular subtypes. There was a statistically significant difference among the nuclear grade, tumour size, nodal status, lymphovascular, and perineural invasion. In the first 5-year period, the OS rate for IDC-NOS and IMPC was 90.8% and 86.2% (p<0.05). The 5-year OS rate of luminal A, luminal B, HER2, triple negative (TN), and IMPC patients was 97.6%, 91.3%, 90%, 70%, and 86.2%, respectively (p<0.05). The OS rate in patients with TN and IMPC was similar which was found significantly lower than the other groups (luminal A, luminal B, and HER2). The median OS was 51.3 months and 53.9 months for the patients with TN and IMPC, respectively (p<0.001). This difference disappeared in the 10th and 15th years of follow-up.

CONCLUSION: The majority of the deaths in IMPC occurred within the first 5 years. The 5-year OS rates were similar in the TN and IMPC patients. The survival pattern of IMPC is parallel with TN, Therefore, clinical, therapeutic, and prognostic evaluation in IMPC can be done like TN.

KEY WORDS: Invasive ductal carcinoma, Invasive micropapillary carcinoma, Survival.}, } @article {pmid36085291, year = {2022}, author = {Karihtala, P and Porvari, K and Roininen, N and Voutilainen, S and Mattson, J and Heikkilä, P and Haapasaari, KM and Selander, K}, title = {Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas.}, journal = {Oncogenesis}, volume = {11}, number = {1}, pages = {53}, pmid = {36085291}, issn = {2157-9024}, abstract = {The pathophysiology and the optimal treatment of breast neuroendocrine tumours (NETs) are unknown. We compared the mutational profiles of breast NETs (n = 53) with those of 724 publicly available invasive ductal carcinoma (IDC) and 98 pancreatic NET (PNET) cases. The only significantly different pathogenetic or unknown variant rate between breast NETs and IDCs was detected in the TP53 (11.3% in breast NETs and 41% in IDCs, adjusted p value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p value 0.045) genes. Between breast NETs and PNETs, different pathogenetic or unknown variant frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p value 0.00050), and GATA3 pathogenetic or unknown variants were only found in 17.0% of breast NETs and 0% in PNETs (adjusted p value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Our results suggest that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd, in breast NETs. In conclusion, breast NETs are indeed a separate breast cancer entity, but their optimal treatment remains to be elucidated.}, } @article {pmid36084562, year = {2022}, author = {Nguyen, TH and El-Helou, E and Pop, CF and Shall, A and Zaiter, M and Naccour, J and Ho, XD and Nguyen, TTH and Nguyen, TMC and Bui, TT and Nguyen, VC and Hoang, H}, title = {Primary invasive ductal carcinoma of axillary accessory breast.}, journal = {International journal of surgery case reports}, volume = {98}, number = {}, pages = {107597}, pmid = {36084562}, issn = {2210-2612}, abstract = {Primary accessory breast cancer is an extremely rare pathology, representing less than 1 % of all breast cancers, and it is found in more than 90 % of cases in the axilla. The diagnosis of accessory axillary breast cancer (AABC) is often late and at an advanced stage with an average delay of 40.5 months. Histological sampling and immunohistochemical results confirm the diagnosis. Most patients are diagnosed with stage II disease or higher, so it is considered to have a poor prognosis. There is no specific management for AABC; it follows the guidelines for orthotopic pectoral breast cancer. We therefore report the case of a 50-year-old woman diagnosed with grade II invasive ductal carcinoma found in accessory axillary breast, treated by wide local resection and sentinel lymph node dissection.}, } @article {pmid36082773, year = {2022}, author = {Ryder, JH and Van Schooneveld, TC and Lyden, E and El Ramahi, R and Stohs, EJ}, title = {The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.}, journal = {Infection control and hospital epidemiology}, volume = {}, number = {}, pages = {1-6}, doi = {10.1017/ice.2022.209}, pmid = {36082773}, issn = {1559-6834}, abstract = {OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance.

DESIGN: Retrospective cohort study from January 2016 to December 2019.

SETTING: Academic quaternary-care referral center.

PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours.

METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score.

RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81).

CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.}, } @article {pmid36082093, year = {2022}, author = {Kimura, A and Yamada, A and Shibata, Y and Inoue, S and Oshi, M and Harada, F and Kadokura, T and Takeuchi, H and Hasegawa, N and Kakuta, Y and Endo, I and Chishima, T}, title = {A case of matrix-producing carcinoma of the breast treated with preoperative chemotherapy.}, journal = {Gland surgery}, volume = {11}, number = {8}, pages = {1424-1430}, pmid = {36082093}, issn = {2227-684X}, abstract = {BACKGROUND: Matrix-producing carcinoma (MPC) is a rare tumor accounting for 0.1% of all breast cancers. Although MPC is usually triple-negative breast cancer, there have been few reports of preoperative chemotherapy for MPC that is considered chemotherapy-resistant. Herein, we report a case of MPC that was successfully treated with preoperative chemotherapy.

CASE DESCRIPTION: The patient was a 47-year-old woman diagnosed with right multiple breast cancer, clinical stage IIA. One of the tumors was identified as MPC and the other was invasive ductal carcinoma. The maximum tumor diameter of MPC was 3.8-cm. On immunohistochemistry, the tumor cells of MPC tested negative for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). The Ki67 index was 90%. Preoperative chemotherapy was performed. EC (epirubicin 90 mg/m[2] and cyclophosphamide 600 mg/m[2]) was administered every 3 weeks for a total of 4 courses, followed by 12 courses of weekly paclitaxel (80 mg/m[2]). Then, she underwent right skin-sparing mastectomy, sentinel lymph node biopsy, and deep inferior epigastric perforator flap reconstruction. There was no metastasis to the sentinel lymph nodes. Postoperative pathological results showed that the residual tumor of the MPC measured only 0.1 cm. On the other hand, the residual tumor of the invasive ductal carcinoma was 0.7 cm. Endocrine therapy with oral tamoxifen was initiated for the invasive ductal carcinoma. Three years after surgery, no recurrence was observed. It has been reported that prognosis was correlated with residual cancer after preoperative chemotherapy. In addition, preoperative chemotherapy is of high clinical significance for the selection of postoperative treatment.

CONCLUSIONS: Although our case of MPC was successfully treated with preoperative chemotherapy, the standard of care for MPC remains uncertain. Development of a new targeted therapy for MPC is warranted.}, } @article {pmid36077795, year = {2022}, author = {Shu, L and Tong, Y and Li, Z and Chen, X and Shen, K}, title = {Can HER2 1+ Breast Cancer Be Considered as HER2-Low Tumor? A Comparison of Clinicopathological Features, Quantitative HER2 mRNA Levels, and Prognosis among HER2-Negative Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {17}, pages = {}, pmid = {36077795}, issn = {2072-6694}, support = {81772797, 82072937//National Natural Science Foundation of China/ ; 20172007//Shanghai Municipal Education Commission/ ; 21YF1427400//Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {Background: Human epidermal growth factor receptor 2 (HER2)-low tumor is a new entity defined as HER2 immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization (FISH)-negative. We aimed to evaluate whether HER2 mRNA levels tested by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) could better define HER2-low tumors. Patients and methods: Consecutive breast cancer patients with hormonal receptor-positive, HER2-negative diseases, and HER2 mRNA results were included. Clinicopathologic features, HER2 mRNA expression level, and prognosis were compared among HER2 0, 1+ and 2+/FISH− groups. Concordance of the HER2 category between qRT-PCR and IHC/FISH was analyzed for each group. Results: 2296 patients were included: 368 (16.0%) HER2 0, 911 (39.7%) 1+, and 1017 (44.3%) 2+/FISH− tumors. HER2 1+ cases shared similarities with HER2 0 tumors in terms of clinicopathologic features (all p > 0.05), whereas IHC 2+/FISH− cases were less often non-IDC (p = 0.045), node-negative (p = 0.044), and Ki-67 < 14% (p <0.001). The mRNA expression was similar between HER2 0 and 1+ cases (p = 0.063), and both were lower than 2+/FISH− cases (p < 0.001). A poor concordance rate was found between IHC/FISH and qRT-PCR for HER2 0 and HER2-low cases (Cohen’s kappa 0.126, p < 0.001). No survival difference was observed among these groups, whether stratified by HER2 IHC/FISH status or mRNA level (all p > 0.05). Conclusions: HER2 1+ cases had similar clinicopathological features to HER2 0 breast cancers, and both were different from HER2 2+/FISH− cases. HER2 mRNA levels were comparable between HER2 0 and 1+ tumors, and both were significantly lower than IHC 2+/FISH− tumors. Neither IHC nor qRT-PCR may be optimal to quantify HER2-low expression, especially for HER2 1+ patients.}, } @article {pmid36074318, year = {2022}, author = {Pellegata, NS and Berriel Diaz, M and Rohm, M and Herzig, S}, title = {Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {3}, pages = {517-547}, pmid = {36074318}, issn = {1573-7233}, mesh = {Adipose Tissue ; *Adrenergic Agents ; Extracellular Matrix ; Humans ; *Neoplasms/epidemiology ; Obesity/complications ; }, abstract = {Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.}, } @article {pmid36072237, year = {2022}, author = {Ahmed, Y and Khan, AMH and Shaukat, F and Tahseen, R and Tariq, M and Mazhar, B and Abrar, S and Ali, N}, title = {Acute dermatitis in adult female patients receiving hypofractionated radiotherapy for breast cancer: experience from a low- and middle-income country.}, journal = {Ecancermedicalscience}, volume = {16}, number = {}, pages = {1412}, pmid = {36072237}, issn = {1754-6605}, abstract = {Radiotherapy (RT) is an important component of treatment in the management of breast cancer patients. The radiation treatment paradigm has been shifted towards hypofractionated RT. This study aims to determine the severity of acute dermatitis in patients receiving hypofractionated RT for breast cancer at a tertiary care university hospital in Pakistan. Patients with biopsy-proven invasive breast carcinoma or DCIS who were referred for radical radiotherapy after discussion in the breast tumour board were retrospectively reviewed. Physical assessment of the patients for evaluation of the severity of radiation dermatitis will be carried out in the first week, last week and on the first follow-up after 1 month of completion of RT, according to the Radiation Therapy Oncology Group/European Organisation For Research And Treatment Of Cancer (RTOG/EORTC) criteria. We identified 92 female patients in 6 months at Aga Khan University Hospital, with a mean age of 53.1 years. Most of the treated patients had clinical stage 3 (64%) cancer, while others were stage 2 (42%), stage 1 (2%) and stage 0 (2%). The surgeries performed were mastectomy in 59 patients and breast-conserving surgery in 33 patients. Histology was Intra Ductal Carcinoma (IDC) (95%), DCIS (3%) and Invasive Lobular Carcinoma (ILC) (2%). Most of the patients received chemotherapy (96%). Radiotherapy dose was 4256 cGy in 16 fractions, followed by a boost of 10 Gy. The radiation techniques used were intensity-modulated radiotherapy (47.8%) and three-dimensional conformal radiotherapy (52.2%). Most of the patients experienced no toxicity (59%), while grade I toxicity was observed in 29% of the patients and grade II toxicity was observed in 11%. Only 1% of the patients experienced grade III skin toxicity. Hypofractionated radiation therapy is beneficial because of the shorter overall treatment time which reduces the socio-economic burden, not only for patients but also for radiotherapeutic institutions. However, extended follow-up is to be reported for long-term toxicity and other consequences.}, } @article {pmid36068624, year = {2022}, author = {Kvopka, M and Smith, JR and Koczwara, B and Lake, SR}, title = {Bilateral intermediate uveitis following treatment with paclitaxel in a patient with invasive ductal carcinoma of the breast.}, journal = {International journal of retina and vitreous}, volume = {8}, number = {1}, pages = {63}, pmid = {36068624}, issn = {2056-9920}, abstract = {BACKGROUND: To report a case of bilateral intermediate uveitis without cystoid macular edema secondary to paclitaxel therapy, and its successful management with oral corticosteroids.

CASE PRESENTATION: A 66-year-old female developed bilateral intermediate uveitis with reduced best corrected visual acuity to 20/40 right and 20/200 left, following 12 cycles of paclitaxel therapy for breast carcinoma. Optical coherence tomography demonstrated no cystoid macular edema in either eye, and fundus fluorescein angiography showed localized retinal vascular leakage. Resolution of uveitis and improvement of visual acuity followed treatment with oral prednisolone for two months. Fourteen months after presentation, right and left visual acuities had returned to 20/32 and 20/40, respectively, and there was no recurrence of the uveitis.

CONCLUSIONS: This is the first reported case of bilateral intermediate uveitis in a patient treated with paclitaxel. Drug-induced uveitis should be considered in patients with visual symptoms in the setting of taxane chemotherapy, and oral corticosteroids are a safe and effective treatment.}, } @article {pmid36065403, year = {2022}, author = {Liu, Y and Jin, Z and Yu, X and Zheng, A and Jin, F and Wang, X}, title = {An insight into the invasion of breast ductal carcinoma in situ based on clinical, pathological and hematological data.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13966}, pmid = {36065403}, issn = {2167-8359}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; *Breast Neoplasms/diagnosis ; Neoplastic Processes ; Lymphatic Metastasis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) has become a non-negligible part of breast cancers owing to the greatly increased incidence. While its natural history was not fully elucidated, which is the reason for current controversies in clinical treatment. Exploration of this issue from a clinical perspective is meaningful.

METHODS: Medical records of 389 patients diagnosed with DCIS or DCIS with invasive ductal carcinoma (IDC) were reviewed. All of them received appropriate medical care in our center. All 324 patients in training cohort were divided into invasion and non-invasion groups based on pathology. Differences in DCIS immunohistochemical markers and hematological indicators between them were analyzed. In the invasion group, differences between DCIS and matched IDC were compared to explore changes in the tumor heterogeneity during invasion. Conclusions are validated in the validation cohort of 65 patients.

RESULTS: Patients in invasion and non-invasion groups were balanced in baseline characteristics and no statistically significant differences were noticed for DCIS immunohistochemical markers. For hematological indicators, high expression of platelet >291.50) (odds ratio, 2.46; CI [1.35-4.46]; p = 0.003) and SII (>347.20) (odds ratio, 2.54; CI [1.56-4.12]; p < 0.001) were established as independent predictors for invasion by logistic analysis and were validated in the validation cohort. Ki-67 of IDC was significantly higher than that of matched DCIS (p < 0.001). HER2 expression and histological grade of DCIS were separately linearly related to those of IDC.

CONCLUSION: The change in hematological indicators is an independent predictor for invasion and can be incorporated into the treatment decision-making process for DCIS. Invasion tumor cells exhibit a stronger proliferative capacity compared with the in-situ ones. There are linear relationships in HER2 expression and histological grades between DCIS and matched IDC. DCIS subclones with different histological grades will develop into invasive carcinomas separately.}, } @article {pmid36065259, year = {2022}, author = {Malakzai, HA and Haidary, AM and Gulzar, S and Haidari, M and Ibrahimkhil, AS and Saadaat, R and Hakimi, A and Sadat Hofiani, SM and Rahmani, S and Abdul-Ghafar, J}, title = {Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {2569-2582}, pmid = {36065259}, issn = {1179-1322}, support = {001/WHO_/World Health Organization/International ; }, abstract = {PURPOSE: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development.

PATIENTS AND METHODS: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan.

RESULTS: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II.

CONCLUSION: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.}, } @article {pmid36060830, year = {2022}, author = {Kroeze, E and Huijsman, R}, title = {One for All, All for One: A Mixed Methods Case Study into the Role Organisational and Personal Interests Play on Cooperation in Dutch Integrated Dementia Care Networks.}, journal = {International journal of integrated care}, volume = {22}, number = {3}, pages = {10}, pmid = {36060830}, issn = {1568-4156}, abstract = {INTRODUCTION: Cooperation is key to provide integrated dementia care. However, different kinds of (personal and organisational) interests will affect collaboration in integrated dementia care (IDC) networks. Hence, it is crucial to understand how interests influence relations in IDC-networks in order to shape future policies.

METHODS: A sequential mixed methods single case study design was used, in three phases: a Social Network Analysis (SNA) based on data from questionnaires (n = 24-26), explorative interviews with network partners (n = 14) and a focus group with network coordinators (n = 7) to explore the conceptual generalisability of the single case of the IDC-network.

RESULTS: The SNA revealed that highly connected organisations were often established care organisations that deliver case management, while smaller care organisations or welfare organisations tend to be less connected. Care-related, strategic, and financial interests influence participation of organisations in the IDC-network, while personal intrinsic motivations determine a representative's contribution to the network. Especially conflicting interests strongly influence the network structure.

DISCUSSION AND CONCLUSION: We conclude that conflicting interests in IDC-networks stand in the way of reaching the collective goal of an IDC-network, i.e., optimising the wellbeing of people with dementia and their informal caregivers in the region. Thus, IDC-networks should act to manage, resolve and prevent disputes arising from conflicting interests.}, } @article {pmid36052460, year = {2022}, author = {Isaogullari, SY and Topal, U and Ozturk, F and Gok, M and Oz, B and Akcan, AC}, title = {The relationship of patients, giving or not giving a pathological full response, wıth YAP (Yes Associated Protein) in breast cancer cases to which neo-adjuvant chemotherapy is applied.}, journal = {Annali italiani di chirurgia}, volume = {92}, number = {}, pages = {263-270}, pmid = {36052460}, issn = {2239-253X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; *Breast Neoplasms/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Ki-67 Antigen ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/drug therapy ; Receptor, ErbB-2/metabolism/therapeutic use ; Receptors, Estrogen/metabolism/therapeutic use ; Receptors, Progesterone/metabolism/therapeutic use ; Retrospective Studies ; YAP-Signaling Proteins ; }, abstract = {AIM: We aimed to evaluate (immunohistochemically) the YAP expression in breast cancer patients undergoing neoadjuvant chemotherapy and to clarify the relationship between the molecular characteristics, treatment response and survival data and the YAP expression, and hence, to clarify the prognostic significance.

MATERIAL AND METHODS: One hundred and four patients who were diagnosed with Breast Cancer between 2015-2020 and underwent Neo Adjuvant Chemotherapy were included in the study. Estrogen Receptor(ER), Progesterone Receptor(PR), Human Epidermal Growth Receptor-2(HER2) and Ki-67. Expression are routinely stained immunohistochemically. In this study, existing immunohistochemical markers were reviewed and also, the relationship of YAP with these biological markers was evaluated by using immunohistochemistry and its effect on prognosis has been investigated.

RESULTS: The average age of the patients was 52.37. While YAP was positive in 78 patients (75%), it was negative in 26 patients (25%). In the evaluation after neoadjuvant therapy, pathological complete response (MillerPayne Grade5 response) in 28 patients (26.9%), relapse in 6 patients (5.8%), and exitus in 6 patients (5.8%) were detected. In the pathological evaluation, invasive Ductal Carcinoma was the most common one observed in 88 patients (84.6%). As a result of the statistical evaluation, no significant result was obtained between the parameters and YAP negative/positive.

CONCLUSION: As a result of staining with additional YAP in patients who were diagnosed with breast cancer and routinely stained with ER, PR, Cerb B2 and Ki-67 in pathology samples, we could not reach a result that would contribute positively to survival. Longer studies to be conducted prospectively will be meaningful.

KEY WORDS: Breast Cancer, Chemotherapy, Neoadjuvant, Yes Associated Protein.}, } @article {pmid36051653, year = {2022}, author = {Yang, X and Chen, L and Shen, Y}, title = {Breast Metaplastic Carcinoma With Osteosarcomatous Differentiation: A Case Report and literature Review.}, journal = {Clinical pathology (Thousand Oaks, Ventura County, Calif.)}, volume = {15}, number = {}, pages = {2632010X221118056}, pmid = {36051653}, issn = {2632-010X}, abstract = {Metaplastic breast carcinoma (MBCs) is a rare heterogeneous group of malignancies. Herein, we report a case of metaplastic breast carcinoma, which had 2 components. One of them was typical invasive ductal carcinoma (IDC), the other one was presenting as osteosarcoma with lots of immature trabeculae. The results of immunohistochemistry showed different presentations between them. The majority of MBCs show triple-negativity for ER, PR, and HER-2 and are thus associated with poor prognosis. Our report shows that, it is necessary to describe the proportion of the components and the presentations of immunohistochemistry in the diagnosis, which will be important to develop specific and effective therapies.}, } @article {pmid36048457, year = {2022}, author = {Tannir, NM and Agarwal, N and Porta, C and Lawrence, NJ and Motzer, R and McGregor, B and Lee, RJ and Jain, RK and Davis, N and Appleman, LJ and Goodman, O and Stadler, WM and Gandhi, S and Geynisman, DM and Iacovelli, R and Mellado, B and Sepúlveda Sánchez, JM and Figlin, R and Powles, T and Akella, L and Orford, K and Escudier, B}, title = {Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial.}, journal = {JAMA oncology}, volume = {8}, number = {10}, pages = {1411-1418}, pmid = {36048457}, issn = {2374-2445}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *Carcinoma, Renal Cell/drug therapy/mortality ; Nivolumab/therapeutic use ; Ipilimumab/therapeutic use ; Glutaminase/therapeutic use ; Double-Blind Method ; Immune Checkpoint Inhibitors ; Glutamine/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Glutamates/therapeutic use ; }, abstract = {IMPORTANCE: Dysregulated metabolism is a hallmark of renal cell carcinoma (RCC). Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor that blocks glutamine utilization and downstream pathways. Preclinically, telaglenastat synergized with cabozantinib, a VEGFR2/MET/AXL inhibitor, in RCC models.

OBJECTIVE: To compare the efficacy and safety of telaglenastat plus cabozantinib (Tela + Cabo) vs placebo plus cabozantinib (Pbo + Cabo).

CANTATA was a randomized, placebo-controlled, double-blind, pivotal trial conducted at sites in the US, Europe, Australia, and New Zealand. Eligible patients had metastatic clear-cell RCC following progression on 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or nivolumab plus ipilimumab. The data cutoff date was August 31, 2020. Data analysis was performed from December 2020 to February 2021.

INTERVENTIONS: Patients were randomized 1:1 to receive oral cabozantinib (60 mg daily) with either telaglenastat (800 mg twice daily) or placebo until disease progression or unacceptable toxicity.

MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by blinded independent radiology review.

RESULTS: A total of 444 patients were randomized: 221 to Tela + Cabo (median [range] age, 61 [21-81] years; 47 [21%] women and 174 [79%] men) and 223 to Pbo + Cabo (median [range] age, 62 [29-83] years; 68 [30%] women and 155 [70%] men). A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy. Median progression-free survival was 9.2 months for Tela + Cabo vs 9.3 months for Pbo + Cabo (HR, 0.94; 95% CI, 0.74-1.21; P = .65). Overall response rates were 31% (69 of 221) with Tela + Cabo vs 28% (62 of 223) with Pbo + Cabo. Treatment-emergent adverse event (TEAE) rates were similar between arms. Grade 3 to 4 TEAEs occurred in 160 patients (71%) with Tela + Cabo and 172 patients (79%) with Pbo + Cabo and included hypertension (38 patients [17%] vs 40 patients [18%]) and diarrhea (34 patients [15%] vs 29 patients [13%]). Cabozantinib was discontinued due to AEs in 23 patients (10%) receiving Tela + Cabo and 33 patients (15%) receiving Pbo + Cabo.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, telaglenastat did not improve the efficacy of cabozantinib in metastatic RCC. Tela + Cabo was well tolerated with AEs consistent with the known risks of both agents.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428217.}, } @article {pmid36045608, year = {2022}, author = {Flosdorf, N and Zenke, M}, title = {Dendritic cells generated from induced pluripotent stem cells and by direct reprogramming of somatic cells.}, journal = {European journal of immunology}, volume = {52}, number = {12}, pages = {1880-1888}, doi = {10.1002/eji.202149550}, pmid = {36045608}, issn = {1521-4141}, mesh = {Humans ; *Induced Pluripotent Stem Cells ; Dendritic Cells ; }, abstract = {Novel and exciting avenues allow generating dendritic cells (DC) by reprogramming of somatic cells. DC are obtained from induced pluripotent stem cells (iPS cells), referred to as ipDC, and by direct reprogramming of cells toward DC, referred to as induced DC (iDC). iPS cells represent pluripotent stem cells generated by reprogramming of somatic cells and can differentiate into all cell types of the body, including DC. This makes iPS cells and ipDC derived thereof useful for studying various DC subsets, acquiring high cell numbers for research and clinical use, or applying genome editing to generate DC with wanted properties. Thereby, ipDC overcome limitations in specific DC subsets, which are only found in low abundance in blood or lymphoid organs. iDC are generated by direct reprogramming of somatic cells with a specific set of transcription factors and offer an avenue to obtain DC without a pluripotent cell intermediate. ipDC and iDC retain patient and disease-specific mutations and this opens new perspectives for studying DC in disease. This review summarizes the current techniques used to generate ipDC and iDC, and the types and functionality of the DC generated.}, } @article {pmid36043708, year = {2022}, author = {Gadi, V and Shetty, SR}, title = {Potential of Anti-inflammatory Molecules in the Chemoprevention of Breast Cancer.}, journal = {Recent advances in inflammation & allergy drug discovery}, volume = {16}, number = {2}, pages = {60-76}, pmid = {36043708}, issn = {2772-2716}, mesh = {Humans ; Female ; *Breast Neoplasms/prevention & control ; Vascular Endothelial Growth Factor A ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Chemoprevention ; *Anticarcinogenic Agents/pharmacology ; Phytochemicals/pharmacology ; }, abstract = {Breast cancer is a global issue, affecting greater than 1 million women per annum. Over the past two decades, there have been numerous clinical trials involving the use of various pharmacological substances as chemopreventive agents for breast cancer. Various pre-clinical as well as clinical studies have established numerous anti-inflammatory molecules, including nonsteroidal anti-inflammatory drugs (NSAIDs) and dietary phytochemicals as promising agents for chemoprevention of several cancers, including breast cancer. The overexpression of COX-2 has been detected in approximately 40% of human breast cancer cases and pre-invasive ductal carcinoma in-situ lesions, associated with aggressive elements of breast cancer such as large size of the tumour, ER/PR negative and HER-2 overexpression, among others. Anti-inflammatory molecules inhibit COX, thereby inhibiting the formation of prostaglandins and inhibiting nuclear factor-κBmediated signals (NF-kB). Another probable explanation entails inflammation-induced degranulation, with the production of angiogenesis-regulating factors, such as vascular endothelial growth factor, which can be possibly regulated by anti-inflammatory molecules. Apart from NSAIDS, many dietary phytochemicals have the ability to decrease, delay, or stop the progression and/or incidence of breast cancer by their antioxidant action, regulating inflammatory and proliferative cell signalling pathways as well as inducing apoptosis. The rapid progress in chemoprevention research has also established innovative strategies that can be implemented to prevent breast cancer. This article gives a comprehensive overview of the recent advancements in using antiinflammatory molecules in the chemoprevention of breast cancer along with their mechanism of action, supported by latest preclinical and clinical data. The merits of anti-inflammatory chemopreventive agents in the prevention of cardiotoxicity have been described. We have also highlighted the ongoing research and advancements in improving the efficacy of using antiinflammatory molecules as chemopreventive agents.}, } @article {pmid36040027, year = {2023}, author = {Thompson, LDR and Bishop, JA}, title = {Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {2}, pages = {112-129}, pmid = {36040027}, issn = {1533-4031}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Salivary Gland Neoplasms/pathology ; Transcription Factors ; Salivary Glands/pathology ; Biomarkers, Tumor/genetics ; }, abstract = {Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.}, } @article {pmid36039062, year = {2022}, author = {Wu, Q and He, L and Luo, J and Jin, W and Xu, Y and Wang, C}, title = {Long-term remission under Disitamab Vedotin (RC48) in HR-positive/HER2-positive metastatic breast cancer with brain meningeal, and bone marrow involvement: A case report.}, journal = {Oncology letters}, volume = {24}, number = {4}, pages = {339}, pmid = {36039062}, issn = {1792-1082}, abstract = {Breast cancer (BC) with overexpression of human epidermal growth factor receptor 2 (HER2) is closely associated with an elevated risk of multiple distant metastases and unfavorable prognosis. Disitamab Vedotin (RC48) is a newly developed antibody-drug conjugate targeting HER2, which is comprised of hertuzumab coupled to monomethyl auristatin E via a cleavable linker. Pre-clinical studies indicated its strong anti-tumor activity in HER2-positive and low HER2 expression models of BC. The present study reported on the case of a 60-year-old postmenopausal female who suffered from fatigue and was diagnosed with a right-sided BC tumor. The diagnosis was stage IV (cT4N3M1) hormone receptor (HR)-positive and HER2-positive invasive ductal carcinoma with systemic metastases (brain included). The patient initially responded well to 26 cycles of the first-line anti-HER2 targeted therapy plus chemotherapy (trastuzumab+pertuzumab+nab-paclitaxel) combined with whole-brain radiotherapy. However, both extracranial and intracranial lesions achieved progressive disease (PD), which eventually occurred during 5 sequential cycles of maintenance therapy. Subsequently, 4 cycles of second-line treatment (trastuzumab + pyrotinib + capecitabin) were continued until the levels of blood tumor markers CEA, CA15-3 and CA125 were elevated, and systemic PD was able to be attained (the brain metastases were rated as stable disease). Finally, the patient received RC48 as the third-line therapy and achieved a durable and effective clinical response. To date, the patient has benefited from 12 cycles of RC48 without any severe adverse effects. The overall survival was >3 years. The present study showcased that RC48 was effective and tolerable for a patient with HR- and HER2-positive BMBC.}, } @article {pmid36034829, year = {2022}, author = {Pillai, SS and Pereira, DG and Bonsu, G and Chaudhry, H and Puri, N and Lakhani, HV and Tirona, MT and Sodhi, K and Thompson, E}, title = {Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {953178}, pmid = {36034829}, issn = {1663-9812}, abstract = {Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.}, } @article {pmid36031887, year = {2022}, author = {Sogunro, O and Sayyed, AA and Aminpour, N and Towfighi, P and Maini, M and Masanam, M and Deldar, R and Murray, A and De La Cruz, L and Greenwalt, I and Son, JD}, title = {Triple negative breast cancer and reconstruction: Predictors of recurrence, complications, and mortality.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {343-350}, doi = {10.3233/BD-220005}, pmid = {36031887}, issn = {1558-1551}, mesh = {*Breast Neoplasms ; Female ; Humans ; *Mammaplasty ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; *Triple Negative Breast Neoplasms ; }, abstract = {BACKGROUND: Only 42% of all breast cancer patients undergoing mastectomy elect for breast reconstruction.

OBJECTIVE: We evaluate factors impacting complications, recurrence, and mortality in triple-negative breast cancer (TNBC) patients undergoing reconstruction.

METHODS: Reconstructive TNBC patients at a single institution from 2010 to 2020 were retrospectively reviewed. Patient demographics, cancer characteristics, reconstruction choice, and complications were collected. Statistical significance was defined at p < 0.05.

RESULTS: A total of 131 patients were identified. Average age was 47.8 years, 50.4% were Caucasian and 36.4% were African American. Most patients had invasive ductal carcinoma (90.8%), and most underwent nipple-sparing (41.2%) or skin-sparing (38.9%) mastectomies. Twenty-one patients (16.0%) experienced postoperative complications. Patients with complications tended to be older (52.1 versus 46.9 years, p = 0.052). At mean follow-up of 52.1 months, 14.5% experienced cancer recurrence and 5.3% died. Deceased patients were significantly younger at diagnosis (42.2 versus 48.5 years, p = 0.008) and had a lower BMI compared to surviving patients (21.2 versus 26.9 kg/m2; p = 0.014). Patients younger than age 45 years had higher Ki-67 than those older than 45 years (80.0% versus 60.0%, p = 0.013). Outcomes in autologous- versus implant-based reconstruction were not significantly different.

CONCLUSIONS: In TNBC post-mastectomy reconstruction patients, age and BMI were predictors of mortality while race, smoking history, reconstruction choice, or type of implant-based reconstruction had no significant effect on these outcomes.

SYNOPSIS: The purpose of this study is to evaluate factors that impact complications, recurrence, and mortality in triple negative breast cancer (TNBC) patients undergoing reconstruction. We identified BMI, neoadjuvant chemotherapy, and age as predictors of complications, recurrence, and mortality in TNBC.}, } @article {pmid36031387, year = {2022}, author = {Rios Garcia, M and Meissburger, B and Chan, J and de Guia, RM and Mattijssen, F and Roessler, S and Birkenfeld, AL and Raschzok, N and Riols, F and Tokarz, J and Giroud, M and Gil Lozano, M and Hartleben, G and Nawroth, P and Haid, M and López, M and Herzig, S and Berriel Diaz, M}, title = {Trip13 Depletion in Liver Cancer Induces a Lipogenic Response Contributing to Plin2-Dependent Mitotic Cell Death.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {9}, number = {29}, pages = {e2104291}, pmid = {36031387}, issn = {2198-3844}, support = {2015_A240//Else-Kröner-Fresenius-Stiftung/ ; //Helmholtz Future Topic AmPro/ ; 2016-PG068//Xunta de Galicia/ ; RTI2018-101840-B-I00//Ministerio de Economía y Competitividad (MINECO) co-funded by FEDER Program of EU/ ; }, mesh = {ATPases Associated with Diverse Cellular Activities/metabolism ; Cell Cycle Proteins/metabolism ; Cell Death ; Humans ; *Insulins/metabolism ; Lipids ; *Liver Neoplasms ; Mad2 Proteins/metabolism ; Paclitaxel/pharmacology ; Perilipin-2 ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Thyroid Hormone/metabolism ; }, abstract = {Aberrant energy metabolism and cell cycle regulation both critically contribute to malignant cell growth and both processes represent targets for anticancer therapy. It is shown here that depletion of the AAA+-ATPase thyroid hormone receptor interacting protein 13 (Trip13) results in mitotic cell death through a combined mechanism linking lipid metabolism to aberrant mitosis. Diminished Trip13 levels in hepatocellular carcinoma cells result in insulin-receptor-/Akt-pathway-dependent accumulation of lipid droplets, which act as functional acentriolar microtubule organizing centers disturbing mitotic spindle polarity. Specifically, the lipid-droplet-coating protein perilipin 2 (Plin2) is required for multipolar spindle formation, induction of DNA damage, and mitotic cell death. Plin2 expression in different tumor cells confers susceptibility to cell death induced by Trip13 depletion as well as treatment with paclitaxel, a spindle-interfering drug commonly used against different cancers. Thus, assessment of Plin2 levels enables the stratification of tumor responsiveness to mitosis-targeting drugs, including clinically approved paclitaxel and Trip13 inhibitors currently under development.}, } @article {pmid36018614, year = {2022}, author = {Sun, Z and Li, L and Sun, C and Ni, Q and Zhao, Y and Wu, H and Jin, H}, title = {Active Control of Interface Dynamics in NASICON-Based Rechargeable Solid-State Sodium Batteries.}, journal = {Nano letters}, volume = {22}, number = {17}, pages = {7187-7194}, doi = {10.1021/acs.nanolett.2c02509}, pmid = {36018614}, issn = {1530-6992}, abstract = {Severe challenges are restraining the practical application of solid-state batteries, such as the dendrite growth and unsatisfactory compatibility between solid electrolyte and electrode. Here, we propose an interface dynamic control (IDC) strategy to ensure the stable operation of NASICON-based solid-state sodium batteries. First, we introduce intergranular phase (CuO) to effectively promote the densification of Na3Zr2Si2PO12 with an optimized ionic conductivity of 1.74 × 10[-3] S cm[-1] at 25 °C. Moreover, the kinetically formed Na-Cu-O interlayer reveals outstanding conductive capability. The dramatically reduced interfacial area-specific resistance (70 ohm cm[-2]) boosts the resistance to Na dendrite growth, ensuring the excellent cycling stability of symmetric Na cells at a current density of 0.4 mA cm[-2] and room temperature. All-solid-state sodium metal batteries with Na3V1.5Cr0.5(PO4)3 cathode and modified Na3Zr2Si2PO12 ceramic electrolyte reveal a high retention of 87.4% at 100 mA g[-1] over 300 cycles. This work opens up a new route for the rational interface design of NASICON-structure solid electrolyte toward the application in the high energy-density and high safety electrochemical energy storage devices.}, } @article {pmid36016722, year = {2022}, author = {Barker, T and D'hulst, P and Fong, E}, title = {Urethro-venous fistula following straddle injury: A case report and image series.}, journal = {Urology case reports}, volume = {45}, number = {}, pages = {102184}, pmid = {36016722}, issn = {2214-4420}, abstract = {We present a case of a 49-year-old man with an acute traumatic urethral injury after a fall onto a fence post. Retrograde contrast study showed a contrast leak and suspicion of a traumatic urethro-venous fistula. We successfully placed a urethral indwelling catheter (IDC) in the operating room and follow-up urethrocystoscopy showed healing of the injury. The patient remained asymptomatic during further follow-up visits.}, } @article {pmid36016067, year = {2022}, author = {Benmussa, C and Cauchard, JR and Yakhini, Z}, title = {Generating Alerts from Breathing Pattern Outliers.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {16}, pages = {}, pmid = {36016067}, issn = {1424-8220}, mesh = {Humans ; Models, Statistical ; *Respiration ; *Respiratory Rate ; Rest ; }, abstract = {Analysing human physiological data allows access to the health state and the state of mind of the subject individual. Whenever a person is sick, having a panic attack, happy or scared, physiological signals will be different. In terms of physiological signals, we focus, in this manuscript, on monitoring breathing patterns. The scope can be extended to also address heart rate and other variables. We describe an analysis of breathing rate patterns during activities including resting, walking, running and watching a movie. We model normal breathing behaviours by statistically analysing signals, processed to represent quantities of interest. We consider moving maximum/minimum, the amplitude and the Fourier transform of the respiration signal, working with different window sizes. We then learn a statistical model for the basal behaviour, per individual, and detect outliers. When outliers are detected, a system that incorporates our approach would send a visible signal through a smart garment or through other means. We describe alert generation performance in two datasets-one literature dataset and one collected as a field study for this work. In particular, when learning personal rest distributions for the breathing signals of 14 subjects, we see alerts generated more often when the same individual is running than when they are tested in rest conditions.}, } @article {pmid36012443, year = {2022}, author = {Kmiecik, A and Ratajczak-Wielgomas, K and Grzegrzółka, J and Romanowicz, H and Smolarz, B and Dziegiel, P}, title = {Expression of NUCB2/NESF-1 in Breast Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012443}, issn = {1422-0067}, support = {STM.A350.20.064//Wrocław Medical University/ ; }, mesh = {*Breast Neoplasms/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Cytoplasm/metabolism ; Female ; Humans ; RNA, Messenger/genetics/metabolism ; }, abstract = {Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.}, } @article {pmid36010848, year = {2022}, author = {Kastora, SL and Kounidas, G and Speirs, V and Masannat, YA}, title = {Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers.}, journal = {Cancers}, volume = {14}, number = {16}, pages = {}, pmid = {36010848}, issn = {2072-6694}, support = {NER11101//NHS Grampian Endowment Fund/ ; }, abstract = {Globally, BC is the most frequently diagnosed cancer in women. The aim of this study was to identify novel secreted biomarkers that may indicate progression to high-grade BC malignancies and therefore predict metastatic potential. A total of 33 studies of breast cancer and 78 of other malignancies were screened via a systematic review for eligibility, yielding 26 datasets, 8 breast cancer secretome datasets, and 18 of other cancers that were included in the comparative secretome analysis. Sequential bioinformatic analysis using online resources enabled the identification of enriched GO_terms, overlapping clusters, and pathway reconstruction. This study identified putative predictors of IDC grade progression and their association with breast cancer patient mortality outcomes, namely, HSPG2, ACTG1, and LAMA5 as biomarkers of in silico pathway prediction, offering a putative approach by which the abovementioned proteins may mediate their effects, enabling disease progression. This study also identified ITGB1, FBN1, and THBS1 as putative pan-cancer detection biomarkers. The present study highlights novel, putative secretome biomarkers that may provide insight into the tumor biology and could inform clinical decision making in the context of IDC management in a non-invasive manner.}, } @article {pmid36010160, year = {2022}, author = {Cho, H and Cho, A and Kang, WJ}, title = {Prognosis Associated with Glycolytic Activity in Regional Lymph Nodes of Patients with Previously Untreated Metastatic Breast Cancer: A Preliminary Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010160}, issn = {2075-4418}, support = {2020M2D9A1093991//Ministry of Science ICT and Future Planning/ ; 6-2019-0112//Yonsei University College of Medicine/ ; }, abstract = {Better mechanisms of predicting prognoses in patients with metastatic breast cancer will improve the identification of patients for whom curative treatments may be the most effective. In this study, the prognostic value of [18]F-fluorodeoxyglucose positron emission tomography/computed tomography ([18]F-FDG PET/CT) was assessed in patients with metastatic breast cancer. A retrospective analysis of women who underwent [18]F-FDG PET/CT for staging of newly diagnosed metastatic breast cancer was conducted. In each patient, the maximum standardized uptake value (SUV) and total lesion glycolysis (TLG) of primary tumors and regional lymph nodes were measured and analyzed for association with survival using the Cox proportional hazards regression model. From 346 consecutive patients, 32 with metastatic invasive ductal carcinoma of the breast were included in the study. The median duration of follow-up was 22.5 months. Disease progression occurred in 26 patients, and 11 patients died. When multivariate analyses with a stepwise forward regression were applied, only the maximum SUV and TLG of regional lymph nodes showed a significant correlation with progression-free survival and overall survival, respectively. This study demonstrates that increased [18]F-FDG uptake in regional lymph nodes is a strong independent predictor of survival in women with metastatic invasive ductal carcinoma of the breast.}, } @article {pmid36009260, year = {2022}, author = {Pigazzani, F and Gorni, D and Dyar, KA and Pedrelli, M and Kennedy, G and Costantino, G and Bruno, A and Mackenzie, I and MacDonald, TM and Tietge, UJF and George, J}, title = {The Prognostic Value of Derivatives-Reactive Oxygen Metabolites (d-ROMs) for Cardiovascular Disease Events and Mortality: A Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009260}, issn = {2076-3921}, abstract = {Oxidative stress participates in the development and exacerbation of cardiovascular diseases (CVD). The ability to promptly quantify an imbalance in an individual reductive-oxidative (RedOx) state could improve cardiovascular risk assessment and management. Derivatives-reactive oxygen metabolites (d-ROMs) are an emerging biomarker of oxidative stress quantifiable in minutes through standard biochemical analysers or by a bedside point-of-care test. The current review evaluates available data on the prognostic value of d-ROMs for CVD events and mortality in individuals with known and unknown CVD. Outcome studies involving small and large cohorts were analysed and hazard ratio, risk ratio, odds ratio, and mean differences were used as measures of effect. High d-ROM plasma levels were found to be an independent predictor of CVD events and mortality. Risk begins increasing at d-ROM levels higher than 340 UCARR and rises considerably above 400 UCARR. Conversely, low d-ROM plasma levels are a good negative predictor for CVD events in patients with coronary artery disease and heart failure. Moreover, combining d-ROMs with other relevant biomarkers routinely used in clinical practice might support a more precise cardiovascular risk assessment. We conclude that d-ROMs represent an emerging oxidative-stress-related biomarker with the potential for better risk stratification both in primary and secondary cardiovascular prevention.}, } @article {pmid36008255, year = {2022}, author = {Cai, Q and Costa, DN and Metter, CK and Goldberg, K and Roehrborn, CG and Cadeddu, J and Pedrosa, I and Meng, X and Mostardeiro, TR and Shah, RB}, title = {Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology.}, journal = {Urologic oncology}, volume = {40}, number = {10}, pages = {452.e1-452.e8}, doi = {10.1016/j.urolonc.2022.07.012}, pmid = {36008255}, issn = {1873-2496}, mesh = {Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Image-Guided Biopsy/methods ; Magnetic Resonance Imaging/methods ; Male ; *Multiparametric Magnetic Resonance Imaging ; Neoplasm Grading ; *Prostatic Neoplasms/diagnostic imaging/surgery ; Retrospective Studies ; }, abstract = {PURPOSE: Accurate preoperative detection of prostate cancer (PCa) exhibiting "cribriform" morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting "cribriform" morphology remains controversial.

MATERIALS AND METHODS: A total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation.

RESULTS: Of the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI.

CONCLUSION: At a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.}, } @article {pmid36002899, year = {2022}, author = {Molinaro, J and DeVries, P and Ha, J and Knight, JM}, title = {New-onset hallucinations with amiodarone: a case report.}, journal = {Annals of general psychiatry}, volume = {21}, number = {1}, pages = {34}, pmid = {36002899}, issn = {1744-859X}, abstract = {BACKGROUND: Amiodarone is a commonly used antiarrhythmic for the treatment of atrial fibrillation with a unique pharmacokinetic profile. While general side effects can be frequently associated with amiodarone, psychiatric adverse reactions to this medication are uncommon. The relationship between amiodarone and hallucinations independent of delirium has been rarely reported in the literature.

CASE PRESENTATION: We report the case of a 63-year-old female with a history of estrogen and progesterone receptor positive invasive ductal carcinoma with osseous metastases to the ribs and skull, major depressive disorder, and unspecified anxiety. She was diagnosed with invasive ductal carcinoma 12 years prior and underwent a lumpectomy with axillary lymph node dissection and radiation, currently maintained on anastrozole and trastuzumab for the past 11 years. Her symptoms of major depressive disorder and anxiety have remained in remission on a regimen of bupropion extended release, duloxetine, and trazodone without recent dose changes. This patient presented to the emergency department with dyspnea and was admitted to the general medical floor with new-onset atrial fibrillation. She was subsequently started on amiodarone for rhythm control. Shortly after its initiation, the patient developed new onset auditory and visual hallucinations with an unremarkable extensive medical evaluation. Auditory hallucinations consisted of music and unintelligible conversations, while visual hallucinations were of a family member crying on the floor and a man carrying a gun. The differential diagnoses included depression with psychotic features, delirium, and amiodarone-induced hallucinations. Given the lack of current depressive symptoms, absence of altered cognition, and the temporal relationship between the initiation of amiodarone and the onset of hallucinations, amiodarone was suspected to be probable etiology of her hallucinations. For this reason, amiodarone was replaced with dronedarone. Visual and auditory hallucinations ceased within less than 3 days after the discontinuation of amiodarone.

CONCLUSIONS: Psychiatric adverse events from amiodarone are uncommon, and associated isolated hallucinations have only been rarely reported in the literature. While the risk of visual and auditory hallucinations appears to be low with amiodarone initiation, clinicians should be aware of this potential side effect.}, } @article {pmid35999153, year = {2022}, author = {Carmon, E and Alster, T and Maly, B and Kadouri, L and Kleinman, TA and Sella, T}, title = {Preoperative MRI for Evaluation of Extent of Disease in IDC Compared to ILC.}, journal = {Clinical breast cancer}, volume = {22}, number = {7}, pages = {e745-e752}, doi = {10.1016/j.clbc.2022.07.007}, pmid = {35999153}, issn = {1938-0666}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/diagnostic imaging/pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVES: The purpose of this study was to assess the incremental value of preoperative breast MRI over mammography and US in depicting the accurate extent of disease in invasive duct carcinoma (IDC) compared to invasive lobular carcinoma (ILC).

PATIENTS AND METHODS: Retrospective analysis of pre-operative mammography, US and MRI was performed in 239 patients with either IDC (n = 193) or ILC (n = 46). Images were evaluated for solitary, multifocal or multi centric disease and compared for concordance with postsurgical pathology. Discordance was documented as either overestimation or underestimation. Two tailed paired T and Fischer's exact tests were used for analysis.

RESULTS: Multifocality was present on pathology in 35% and 61% of patients with IDC and ILC (P < .05) and multicentricity in 23% and 41% respectively (P = .84). In ILC, MRI demonstrated better concordance with pathology compared to mammography and US (89%, 44%, 49% for multifocality [P < .05] and 80.5%, 63%, 71% for multicentricity [P = .3]). For IDC, concordance with pathology for all modalities was similar (65%-76%). Among discordant cases, underestimation was significantly more common for mammography and US, while MRI more frequently overestimated disease extent. MRI very rarely overestimated multifocal disease in ILC (2%).

CONCLUSION: MRI demonstrates an 80% to 90% concordance rate with pathology for ILC, superior to mammography and US. The addition of MRI in IDC patients may decrease underestimation of disease extent and potentially contribute to a reduction in post-operative residual disease.}, } @article {pmid35996660, year = {2022}, author = {Shakuf, V and Ben-David, B and Wegner, TGG and Wesseling, PBC and Mentzel, M and Defren, S and Allen, SEM and Lachmann, T}, title = {Processing emotional prosody in a foreign language: the case of German and Hebrew.}, journal = {Journal of cultural cognitive science}, volume = {6}, number = {3}, pages = {251-268}, pmid = {35996660}, issn = {2520-1018}, abstract = {UNLABELLED: This study investigated the universality of emotional prosody in perception of discrete emotions when semantics is not available. In two experiments the perception of emotional prosody in Hebrew and German by listeners who speak one of the languages but not the other was investigated. Having a parallel tool in both languages allowed to conduct controlled comparisons. In Experiment 1, 39 native German speakers with no knowledge of Hebrew and 80 native Israeli speakers rated Hebrew sentences spoken with four different emotional prosodies (anger, fear, happiness, sadness) or neutral. The Hebrew version of the Test for Rating of Emotions in Speech (T-RES) was used for this purpose. Ratings indicated participants' agreement on how much the sentence conveyed each of four discrete emotions (anger, fear, happiness and sadness). In Experient 2, 30 native speakers of German, and 24 Israeli native speakers of Hebrew who had no knowledge of German rated sentences of the German version of the T-RES. Based only on the prosody, German-speaking participants were able to accurately identify the emotions in the Hebrew sentences and Hebrew-speaking participants were able to identify the emotions in the German sentences. In both experiments ratings between the groups were similar. These findings show that individuals are able to identify emotions in a foreign language even if they do not have access to semantics. This ability goes beyond identification of target emotion; similarities between languages exist even for "wrong" perception. This adds to accumulating evidence in the literature on the universality of emotional prosody.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41809-022-00107-x.}, } @article {pmid35995898, year = {2022}, author = {Bridge, CP and Gorman, C and Pieper, S and Doyle, SW and Lennerz, JK and Kalpathy-Cramer, J and Clunie, DA and Fedorov, AY and Herrmann, MD}, title = {Highdicom: a Python Library for Standardized Encoding of Image Annotations and Machine Learning Model Outputs in Pathology and Radiology.}, journal = {Journal of digital imaging}, volume = {35}, number = {6}, pages = {1719-1737}, pmid = {35995898}, issn = {1618-727X}, support = {P41EB028741/EB/NIBIB NIH HHS/United States ; R01 CA241817/CA/NCI NIH HHS/United States ; HHSN26110071/CA/NCI NIH HHS/United States ; U24 CA264044/CA/NCI NIH HHS/United States ; 5P41EB015902/NH/NIH HHS/United States ; 5R01CA235589/NH/NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; P41 EB015902/EB/NIBIB NIH HHS/United States ; U01CA242879/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Ecosystem ; Data Curation ; *Radiology ; *Radiology Information Systems ; Tomography, X-Ray Computed ; Machine Learning ; }, abstract = {Machine learning (ML) is revolutionizing image-based diagnostics in pathology and radiology. ML models have shown promising results in research settings, but the lack of interoperability between ML systems and enterprise medical imaging systems has been a major barrier for clinical integration and evaluation. The DICOM[®] standard specifies information object definitions (IODs) and services for the representation and communication of digital images and related information, including image-derived annotations and analysis results. However, the complexity of the standard represents an obstacle for its adoption in the ML community and creates a need for software libraries and tools that simplify working with datasets in DICOM format. Here we present the highdicom library, which provides a high-level application programming interface (API) for the Python programming language that abstracts low-level details of the standard and enables encoding and decoding of image-derived information in DICOM format in a few lines of Python code. The highdicom library leverages NumPy arrays for efficient data representation and ties into the extensive Python ecosystem for image processing and machine learning. Simultaneously, by simplifying creation and parsing of DICOM-compliant files, highdicom achieves interoperability with the medical imaging systems that hold the data used to train and run ML models, and ultimately communicate and store model outputs for clinical use. We demonstrate through experiments with slide microscopy and computed tomography imaging, that, by bridging these two ecosystems, highdicom enables developers and researchers to train and evaluate state-of-the-art ML models in pathology and radiology while remaining compliant with the DICOM standard and interoperable with clinical systems at all stages. To promote standardization of ML research and streamline the ML model development and deployment process, we made the library available free and open-source at https://github.com/herrmannlab/highdicom .}, } @article {pmid35985745, year = {2022}, author = {Lerttiendamrong, B and Vongsaisuwon, M}, title = {First report of bilateral synchronous male accessory breast cancer.}, journal = {BMJ case reports}, volume = {15}, number = {8}, pages = {}, pmid = {35985745}, issn = {1757-790X}, mesh = {Axilla/pathology ; *Breast Diseases/surgery ; *Breast Neoplasms/pathology ; *Breast Neoplasms, Male/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Exanthema ; Humans ; Lymph Node Excision ; Male ; Mastectomy ; }, abstract = {Accessory breast occurs due to the persistence of milk line in the non-thoracic region. Malignant transformation in male accessory breast is very rare, with 16 reports documented across the world. No bilateral synchronous accessory male breast cancer has been reported. We present the first case reported globally of a man in his 70s with a complaint of left axillary lump and chronic rash for 3 years. About 1 year ago, additional reddish rash was detected in the right axilla. Initial skin biopsy from a private hospital confirmed mammary carcinoma with skin invasion. Subsequent left breast mastectomy with left axillary lymph node dissection and right wide excision was performed. Final pathological result was grade 2 invasive ductal carcinoma in the left accessory breast and Paget's disease in the contralateral axilla. Postoperative treatment of adjuvant paclitaxel and trastuzumab was prescribed, which was followed by adjuvant radiation therapy.}, } @article {pmid35983810, year = {2022}, author = {Kalemci, S and Kizilay, F and Simsir, A and Emre Ergun, K and Kose, T}, title = {The Influence of the Intraductal Carcinoma of the Prostate on the Short-Term Oncological Outcomes.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {5}, pages = {405-409}, doi = {10.37554/en-j.arch.esp.urol-20210522-3503-23}, pmid = {35983810}, issn = {0004-0614}, mesh = {Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Humans ; Male ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; *Prostatic Neoplasms/pathology ; Retrospective Studies ; }, abstract = {AIM: The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse biochemical recurrence-free survival, higher grade and stage disease. This study aimed to investigate the effect of IDC-P in radical prostatectomy specimens on short-term oncological outcomes.

MATERIALS AND METHODS: Patients who underwent RP at our clinic for prostate cancer between May 2016 and November 2019 were included in the study. They were divided into two groups based on the presence of IDC-P in RP specimens. Their clinical, pathological, and oncologic data were evaluated retrospectively.

RESULTS: A total of 98 patients underwent RP with a mean age of 65.5 years (50-83) and a mean follow-up time of 31.2 months (6-52). Seventy and 28 patients were evaluated in the group without IDC-P and group with IDC-P, respectively. Surgical margin positivity (p=0.307) and lymph node metastasis (p=0.017) rates were higher in the group with IDC-P. Although there were no statistical differences between the groups, at follow-up biochemical recurrence rate (p=0.052) was higher, and mean time to biochemical recurrence rates were lower (p=0.057) in the group with IDC-P. The group with IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality to the group without IDC-P (p=0.037).

CONCLUSIONS: Patients with IDC-P at RP specimens have more advanced disease, shorter biochemical recurrence-free, and cancerspecific survival than those without IDC-P. Defining the presence of IDC-P in RP specimens is critical in choosing the appropriate treatment strategy and predicting the prognosis.}, } @article {pmid35982591, year = {2022}, author = {Kovalenko, I and Roy, P and Soni, B and Sangha, L and Toom, S}, title = {Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e936665}, pmid = {35982591}, issn = {1941-5923}, mesh = {*Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma/pathology ; *Carcinoma, Ductal/genetics/surgery ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mastectomy ; Translocation, Genetic ; }, abstract = {BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.}, } @article {pmid35978202, year = {2022}, author = {Birnbaum, GE and Zholtack, K and Ayal, S}, title = {Is Infidelity Contagious? Online Exposure to Norms of Adultery and Its Effect on Expressions of Desire for Current and Alternative Partners.}, journal = {Archives of sexual behavior}, volume = {51}, number = {8}, pages = {3919-3930}, pmid = {35978202}, issn = {1573-2800}, mesh = {Humans ; *Extramarital Relations ; *Sexual Partners ; Marriage ; Motivation ; Deception ; Interpersonal Relations ; Sexual Behavior ; }, abstract = {Research exploring the determinants of infidelity has mainly focused on individual and relationship characteristics that render relationships vulnerable, paying less attention to the external circumstances that increase the likelihood of straying. The present research examined whether online exposure to norms of adultery would affect expressions of desire for alternative mates. In three studies, romantically involved participants were exposed to others' cheating behavior and then thought of or encountered attractive strangers. Their relationship perceptions and reactions during these experiences (fantasmatic themes, expressed interest in alternative partners, and overt flirtation with them in Studies 1-3, respectively) were recorded. Results showed that following exposure to others' cheating behavior, participants were less likely to devalue the attractiveness of alternative partners and to be committed to their relationship. These findings suggest that exposure to adultery norms decreases the awareness of long-term priorities of relationship maintenance, lessening the resistance to the temptation of attractive alternatives.}, } @article {pmid35976519, year = {2023}, author = {Eum, SY and Schurhoff, N and Teglas, T and Wolff, G and Toborek, M}, title = {Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.}, journal = {Molecular and cellular biochemistry}, volume = {478}, number = {3}, pages = {581-595}, pmid = {35976519}, issn = {1573-4919}, support = {DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Catenins/genetics ; *Circadian Rhythm ; Gene Expression Regulation ; }, abstract = {We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.}, } @article {pmid35969492, year = {2022}, author = {Li, C and Su, N and Wu, H and Liu, C and Che, G and Dong, H}, title = {Synergies of Adjacent Sites in Atomically Dispersed Ruthenium toward Achieving Stable Hydrogen Evolution.}, journal = {Inorganic chemistry}, volume = {61}, number = {34}, pages = {13453-13461}, doi = {10.1021/acs.inorgchem.2c01908}, pmid = {35969492}, issn = {1520-510X}, abstract = {It is a challenge to fabricate atomically dispersed metal clusters in polymeric carbon nitride (PCN) for durable photocatalytic reactions owing to the thermodynamic stability limitation. Herein, atomically dispersed Ru clusters are implanted into the PCN skeleton matrix based on an ionic diffusion and coordination (IDC) strategy, the stability of which is improved owing to the robust Ru-N bonds in the formed RuN4 and RuN3 configurations. Additionally, RuN4 and RuN3 as charge transport bridges between two adjacent melon strands efficaciously conquer hydrogen bond restriction in the skeleton to facilitate the in-plane mobility and separation of charge carriers. Moreover, the synergistic effect of adjacent Ru atoms is triggered on the assembled RuN3-RuN4 and RuN3-RuN3 in the atomically dispersed Ru clusters to significantly decrease hydrogen adsorption energy. As a result, the optimal PCN-Ru photocatalyst achieves nearly 6 times higher than the photocatalytic hydrogen evolution (PHE) rate of the Pt/PCN benchmark and maintains the long-term stable running for 104 h of 26 cycles; its overall PHE performance is far superior to the most of single atoms supported on g-C3N4 photocatalysts reported. The findings here gain new insight into the preparation strategy, structure configuration, and reaction mechanism for atomically dispersed metal clusters supported on PCN, which further stimulates the intensive investigations toward developing more efficient and stable PCN-like photocatalytic materials.}, } @article {pmid35963427, year = {2022}, author = {Brecklinghaus, T and Albrecht, W and Duda, J and Kappenberg, F and Gründler, L and Edlund, K and Marchan, R and Ghallab, A and Cadenas, C and Rieck, A and Vartak, N and Tolosa, L and Castell, JV and Gardner, I and Halilbasic, E and Trauner, M and Ullrich, A and Zeigerer, A and Demirci Turgunbayer, Ö and Damm, G and Seehofer, D and Rahnenführer, J and Hengstler, JG}, title = {In vitro/in silico prediction of drug induced steatosis in relation to oral doses and blood concentrations by the Nile Red assay.}, journal = {Toxicology letters}, volume = {368}, number = {}, pages = {33-46}, doi = {10.1016/j.toxlet.2022.08.006}, pmid = {35963427}, issn = {1879-3169}, mesh = {*Chemical and Drug Induced Liver Injury/etiology ; *Drug-Related Side Effects and Adverse Reactions ; *Fatty Liver/chemically induced ; Hepatocytes ; Humans ; Oxazines/toxicity ; }, abstract = {The accumulation of lipid droplets in hepatocytes is a key feature of drug-induced liver injury (DILI) and can be induced by a subset of hepatotoxic compounds. In the present study, we optimized and evaluated an in vitro technique based on the fluorescent dye Nile Red, further named Nile Red assay to quantify lipid droplets induced by the exposure to chemicals. The Nile Red assay and a cytotoxicity test (CTB assay) were then performed on cells exposed concentration-dependently to 60 different compounds. Of these, 31 were known to induce hepatotoxicity in humans, and 13 were reported to also cause steatosis. In order to compare in vivo relevant blood concentrations, pharmacokinetic models were established for all compounds to simulate the maximal blood concentrations (Cmax) at therapeutic doses. The results showed that several hepatotoxic compounds induced an increase in lipid droplets at sub-cytotoxic concentrations. To compare how well (1) the cytotoxicity test alone, (2) the Nile Red assay alone, and (3) the combination of the cytotoxicity test and the Nile Red assay (based on the lower EC10 of both assays) allow the differentiation between hepatotoxic and non-hepatotoxic compounds, a previously established performance metric, the Toxicity Separation Index (TSI) was calculated. In addition, the Toxicity Estimation Index (TEI) was calculated to determine how well blood concentrations that cause an increased DILI risk can be estimated for hepatotoxic compounds. Our findings indicate that the combination of both assays improved the TSI and TEI compared to each assay alone. In conclusion, the study demonstrates that inclusion of the Nile Red assay into in vitro test batteries may improve the prediction of DILI compounds.}, } @article {pmid35962150, year = {2022}, author = {Berkowitz, SJ and Kwan, D and Cornish, TC and Silver, EL and Thullner, KS and Aisen, A and Bui, MM and Clark, SD and Clunie, DA and Eid, M and Hartman, DJ and Ho, K and Leontiev, A and Luviano, DM and O'Toole, PE and Parwani, AV and Pereira, NS and Rotemberg, V and Vining, DJ and Gaskin, CM and Roth, CJ and Folio, LR}, title = {Interactive Multimedia Reporting Technical Considerations: HIMSS-SIIM Collaborative White Paper.}, journal = {Journal of digital imaging}, volume = {35}, number = {4}, pages = {817-833}, pmid = {35962150}, issn = {1618-727X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Communication ; Diagnostic Imaging ; Electronic Health Records ; Humans ; *Medicine ; Multimedia ; *Radiology Information Systems ; }, abstract = {Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting.}, } @article {pmid35960332, year = {2023}, author = {De Jaeghere, EA and Tuyaerts, S and Van Nuffel, AMT and Belmans, A and Bogaerts, K and Baiden-Amissah, R and Lippens, L and Vuylsteke, P and Henry, S and Trinh, XB and van Dam, PA and Aspeslagh, S and De Caluwé, A and Naert, E and Lambrechts, D and Hendrix, A and De Wever, O and Van de Vijver, KK and Amant, F and Vandecasteele, K and Denys, HG}, title = {Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {72}, number = {2}, pages = {475-491}, pmid = {35960332}, issn = {1432-0851}, support = {1195919N//Fonds Wetenschappelijk Onderzoek/ ; T002218N//Fonds Wetenschappelijk Onderzoek/ ; ZKD5584//Kom op tegen Kanker/ ; G0H7516N//ERA-NET-Transcan-2/ ; SW/OPS/SUB 11719-0001//Nationale Loterij/ ; }, mesh = {Female ; Humans ; *Uterine Cervical Neoplasms/drug therapy ; Quality of Life ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Endometrial Neoplasms/pathology ; }, abstract = {A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0-31.0) in cervical cancer and 12.0% (90% CI 3.4-28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1-25.7) in cervical cancer and 3.6 weeks (95% CI 3.6-15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0-67.0) and 37.4 weeks (95% CI 19.0-50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).}, } @article {pmid35958350, year = {2022}, author = {Fujita, K and Okamura, M and Imakita, T and Yamamoto, Y and Sawai, S and Moriyoshi, K and Mio, T}, title = {Natural course of pulmonary hyalinizing granuloma over a decade.}, journal = {Respiratory medicine case reports}, volume = {39}, number = {}, pages = {101715}, pmid = {35958350}, issn = {2213-0071}, abstract = {BACKGROUND: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response.

CASE PRESENTATION: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG.

CONCLUSIONS: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.}, } @article {pmid35953564, year = {2023}, author = {Telha, W and Abotaleb, B and Zhang, J and Bi, R and Zhu, S and Jiang, N}, title = {Correlation between mandibular anatomy and bad split occurrence during bilateral sagittal split osteotomy: a three-dimensional study.}, journal = {Clinical oral investigations}, volume = {27}, number = {3}, pages = {1035-1042}, pmid = {35953564}, issn = {1436-3771}, mesh = {Humans ; *Osteotomy, Sagittal Split Ramus/methods ; *Mandible/surgery ; Cortical Bone/anatomy & histology ; Molar ; Tooth Root ; Polymers ; }, abstract = {OBJECTIVES: This study aimed to find out the correlation between different anatomical parameters of the mandible and the occurrence of a bad split in patients who had undergone bilateral split sagittal ramus osteotomy (BSSRO).

MATERIALS AND METHOD: At both the distal roots of the first molar (1) and the retromolar area (2), we measured the distance from the buccal margin of the inferior dental canal (IDC) to the buccal margin of the cortical bone (MCBC), the thickness of both buccal cortical (WBCB) and cancellous bone (WBCA), distance from the superior border of IDC to the alveolar crest (MCAC), buccolingual thickness (BLT), and thickness of cancellous bone (WCA). At the ramus, the distances between the sigmoid notch to the upper part of the lingula (SL) and the inferior border of the mandible (SIBM), the thickness of the ramus at the level of the lingula (BLTR), and the anteroposterior width of the ramus (APWR) were measured. The paired and independent t-tests were used when applicable, and a P-value < 0.05 was considered significant.

RESULTS: MCBC1 showed a significant difference between bad and non-bad split sides (P = 0.037). Both WBCA1 and WBCA2 show the same significant difference (P = 0.023, 0.024). Similarly, WCA1 and WCA2 showed a statistical difference between the bad and non-bad split sides (P = 0.027, 0.036). There were no statistically significant differences between the compared sides of WBCB1, WBCB2, MCAC1, MCAC2, SIBM, APWR, SL, and BLTR.

CONCLUSION: Narrow space between IDC and the buccal cortical margin, along with the decrease in the thickness of both buccal cancellous bone and total cancellous bone at the inferior border of the mandible along the course of SSRO, has been implicated in the occurrence of bad split intraoperatively.}, } @article {pmid35950920, year = {2022}, author = {Nardone, A and Qiu, X and Spisak, S and Nagy, Z and Feiglin, A and Feit, A and Cohen Feit, G and Xie, Y and Font-Tello, A and Guarducci, C and Hermida-Prado, F and Syamala, S and Lim, K and Munoz Gomez, M and Pun, M and Cornwell, M and Liu, W and Ors, A and Mohammed, H and Cejas, P and Brock, JB and Freedman, ML and Winer, EP and Fu, X and Schiff, R and Long, HW and Metzger Filho, O and Jeselsohn, R}, title = {A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3673-3686}, pmid = {35950920}, issn = {1538-7445}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; P01 CA250959/CA/NCI NIH HHS/United States ; R01 CA237414/CA/NCI NIH HHS/United States ; R01 CA193910/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Prognosis ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.}, } @article {pmid35949419, year = {2022}, author = {Luo, Y and Ma, A and Huang, S and Yu, Y}, title = {Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis.}, journal = {Breast care (Basel, Switzerland)}, volume = {17}, number = {3}, pages = {296-305}, pmid = {35949419}, issn = {1661-3791}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis.

METHODS: We evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's χ[2] test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS).

RESULTS: Overall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2- subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2- subtype (OS, hazard ratio: 1.501, 95% CI 1.270-1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281-1.825, p < 0.001), lower histological grade (I-II) (OS, hazard ratio: 1.411, 95% CI 1.184-1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235-1.791, p < 0.001), or tumor burden, such as T0-2 (OS, hazard ratio: 1.693, 95% CI 1.368-2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405-2.205, p < 0.001) and N1-2 (OS, hazard ratio: 1.451, 95% CI 1.171-1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187-1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients.

CONCLUSION: Patients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.}, } @article {pmid35949409, year = {2022}, author = {Aryal, V and Singh, M and Neupane, K and Marhatta, A and Amatya, KS and Dhakal, HP}, title = {Invasive ductal carcinoma of breast with neuroendocrine differentiation: A case report.}, journal = {Clinical case reports}, volume = {10}, number = {8}, pages = {e6171}, pmid = {35949409}, issn = {2050-0904}, abstract = {Primary invasive breast carcinoma with neuroendocrine differentiation is an uncommon presentation. We hereby report a case diagnosed as invasive ductal carcinoma with neuroendocrine differentiation in a 52-year-old female patient who presented with a painless right breast lump.}, } @article {pmid35945526, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {872}, pmid = {35945526}, issn = {1471-2407}, support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; }, mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; }, abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.

METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).

RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram.

CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.}, } @article {pmid35943969, year = {2022}, author = {Boyd, CJ and Salibian, AA and Bekisz, JM and Axelrod, DM and Guth, AA and Shapiro, RL and Schnabel, FR and Karp, NS and Choi, M}, title = {Long-Term Cancer Recurrence Rates following Nipple-Sparing Mastectomy: A 10-Year Follow-Up Study.}, journal = {Plastic and reconstructive surgery}, volume = {150}, number = {}, pages = {13S-19S}, doi = {10.1097/PRS.0000000000009495}, pmid = {35943969}, issn = {1529-4242}, mesh = {*Breast Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; *Mastectomy, Subcutaneous/adverse effects ; Neoplasm Recurrence, Local/pathology ; Nipples/pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Despite the increased use of nipple-sparing mastectomies, there are limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who underwent therapeutic nipple-sparing mastectomy with a median of 10 years of follow-up.

METHODS: All patients undergoing nipple-sparing mastectomy at a single institution were retrospectively reviewed temporally to obtain a median of 10 years of follow-up. Patient demographic factors, mastectomy specimen pathologic findings, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence.

RESULTS: One hundred twenty-six therapeutic nipple-sparing mastectomies were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4 percent) and ductal carcinoma in situ (38.1 percent). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0 percent and 10.3 percent of nipple-sparing mastectomy specimens, respectively. Sentinel lymph node biopsy was performed in 84.9 percent of nipple-sparing mastectomies, and 17.8 percent were positive. The rate of positive frozen subareolar biopsy was 7.3 percent (n = 82) and that of permanent subareolar pathology was 9.5 percent (n = 126). The most frequently observed pathologic tumor stages were stage I (44.6 percent) and stage 0 (33.9 percent). The incidence of recurrent disease was 3.17 percent per mastectomy and 3.33 percent per patient. On univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence.

CONCLUSIONS: Overall recurrence rates are low in patients undergoing nipple-sparing mastectomy at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence.

Risk, III.}, } @article {pmid35943964, year = {2022}, author = {Sorotos, M and Paolini, G and D'Orsi, G and Firmani, G and Timmermans, FW and Santanelli di Pompeo, F}, title = {Oncologic Outcome of 1000 Postmastectomy Breast Reconstructions with Fat Transfer: A Single-Center, Matched Case-Control Study.}, journal = {Plastic and reconstructive surgery}, volume = {150}, number = {}, pages = {4S-12S}, doi = {10.1097/PRS.0000000000009494}, pmid = {35943964}, issn = {1529-4242}, mesh = {Adipose Tissue/pathology ; *Breast Neoplasms/etiology ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; *Mammaplasty/adverse effects ; Mastectomy/adverse effects ; Neoplasm Recurrence, Local/epidemiology/etiology/prevention & control ; Retrospective Studies ; }, abstract = {BACKGROUND: Autologous fat transfer has an important role in breast reconstructive surgery. Nevertheless, some concerns remain with regard to its oncologic safety. The authors present a single-center, case-matching study analyzing the impact of autologous fat transfer in the cumulative incidence of local recurrences.

METHODS: From a prospectively maintained database, the authors identified 902 patients who underwent 1025 breast reconstructions from 2005 to 2017. Data regarding demographics, tumor characteristics, surgery details, and follow-up were collected. Exclusion criteria were patients with distant metastases at diagnosis, recurrent tumor, or incomplete data regarding primary tumor; and patients who underwent prophylactic mastectomies and breast-conserving operations. Statistical analysis was conducted to evaluate the impact of the variables on the incidence of local recurrence. A value of p < 0.05 was considered statistically significant.

RESULTS: After 1: n case-matching, we selected 919 breasts, of which 425 patients (46.2 percent) received at least one autologous fat transfer session versus 494 control cases (53.8 percent). Local recurrences had an overall rate of 6.8 percent, and we found local recurrences in 14 autologous fat transfer cases (3.0 percent) and 54 controls (9.6 percent). Statistical analysis showed that autologous fat transfer did not increase the risk of local recurrences (hazard ratio, 0.337; CI, 0.173 to 0.658; p = 0.00007). Multivariate analysis identified invasive ductal carcinoma subtype and lymph node metastases to have an increased risk of local recurrences (hazard ratio >1). Conversely, positive hormonal receptor status was associated with a reduced risk of events (hazard ratio <1).

CONCLUSIONS: Autologous fat transfer was not associated with a higher probability of locoregional recurrence in patients undergoing breast reconstruction; therefore, it can be safely used for total breast reconstruction or aesthetic refinements.

Risk, II.}, } @article {pmid35942356, year = {2022}, author = {Kufel, WD and Blaine, BE and Avery, LM}, title = {Pharmacy students' knowledge and confidence of COVID-19 following an interactive didactic class.}, journal = {Journal of the American College of Clinical Pharmacy : JACCP}, volume = {5}, number = {10}, pages = {1082-1087}, pmid = {35942356}, issn = {2574-9870}, abstract = {BACKGROUND: COVID-19 education for the pharmacy workforce is important to ensure pharmacists are optimizing patient care for the prevention and management of COVID-19. However, there are currently no reports to our knowledge of education and training experiences for COVID-19 prevention and management in the Doctor of Pharmacy (PharmD) curricula.

OBJECTIVE: To evaluate pharmacy students' knowledge and confidence regarding COVID-19 prevention and management before and after an interactive didactic class (IDC).

METHODS: A multicenter, quasi-experimental, cross-sectional survey study was performed among pharmacy students before and after IDC on COVID-19 at two schools of pharmacy. The IDC on COVID-19 consisted of student-led presentations on a COVID-19 drug, an infectious disease pharmacist faculty-led interactive lecture on COVID-19 prevention and management, and clinical case vignettes to assess COVID-19 management strategies. An anonymous, voluntary, electronic survey was distributed to students (n = 85) before and after. The pre- and postintervention survey contained 10 COVID-19 knowledge-based questions and multi-step, 5-point Likert scale statements related to COVID-19 prevention and management confidence. The postintervention survey also evaluated students' perceptions of the COVID-19 IDC. Descriptive statistics were performed, and Student t test was used to compare pre- and postintervention responses.

RESULTS: About 61 surveys were completed resulting in a response rate of 72%. COVID-19 knowledge scores (mean ± SD) increased overall following the IDC (5.9 ± 1.31 vs 8.6 ± 1.29). Pharmacy students' COVID-19 confidence scores (mean ± SD) also improved following the IDC (2.66 ± 0.75 vs 4.03 ± 0.53). Students performed well on the COVID-19 clinical case vignettes with a mean ± SD score of 22.41 ± 0.46 out of 25. Pharmacy students' perceptions of the IDC on COVID-19 were also positive overall.

CONCLUSION: Pharmacy students' knowledge and confidence of COVID-19 prevention and management improved following an IDC. This may be an effective strategy to provide COVID-19 education during the PharmD curricula.}, } @article {pmid35932126, year = {2022}, author = {Yaltirik Bilgin, E and Unal, O and Ciledag, N}, title = {Vasogenic Edema Pattern in Brain Metastasis.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {32}, number = {8}, pages = {1020-1025}, doi = {10.29271/jcpsp.2022.08.1020}, pmid = {35932126}, issn = {1681-7168}, mesh = {Brain/pathology ; *Brain Edema/diagnostic imaging/etiology ; *Brain Neoplasms/complications/diagnostic imaging/pathology ; Cross-Sectional Studies ; Edema/etiology ; Humans ; *Lung Neoplasms/complications ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: To determine the relationship of the presence and amount of vasogenic edema with origin, type, and grade of primary cancer.

STUDY DESIGN: Cross-sectional study.

PLACE AND DURATION OF STUDY: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiology Clinic, Ankara, Turkey, from July 2017 to October 2021.

METHODOLOGY: Brain MRI scans of 292 patients were retrospectively evaluated. Age, gender, origin, type, and grade of primary cancer were determined. Metastasis type, and presence of vasogenic edema accompanying metastatic lesion were questioned. In cases of vasogenic edema accompanying metastatic lesions, the largest diameter of the vasogenic edema mass complex was measured in T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured, and the edema-mass ratio (EMR) was calculated by proportioning the diameter of the edema mass complex to the diameter of the mass.

RESULTS: The frequency of vasogenic edema was found higher in patients with lung cancer compared to other primaries. The EMR was found statistically significantly higher in patients with primary lung cancer (p=0.001). This was particularly evident in the adenocarcinoma group. In the patient group with primary breast cancer, EMR was found significantly lower in patients with invasive ductal carcinoma. (IDC→1.95±0.66 vs. Other→2.48±0.52, Z=-2.301, p=0.021).

CONCLUSION: The amount and presence of vasogenic edema in patients with brain metastases may differ according to the origin and type of primary tumour.

KEY WORDS: Brain edema, Metastatic disease, Magnetic resonance imaging.}, } @article {pmid35929120, year = {2023}, author = {Kim, KN and Salerno, M and Shah, PD and Matro, J and LaRiviere, MJ}, title = {Severe acute radiation dermatitis after palbociclib therapy in the setting of palliative radiotherapy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {29}, number = {3}, pages = {764-767}, doi = {10.1177/10781552221118841}, pmid = {35929120}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; Retrospective Studies ; Pyridines/adverse effects ; *Breast Neoplasms/drug therapy/radiotherapy/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Dermatitis/drug therapy/etiology ; Protein Kinase Inhibitors/therapeutic use ; }, abstract = {INTRODUCTION: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT.

CASE REPORT: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib. A 49-year-old woman with newly diagnosed hormone receptor-positive invasive ductal carcinoma of the left breast presented with lytic bone lesions in the left femur and lumbar spine. The patient initiated treatment with goserelin, tamoxifen, and palbociclib. She underwent prophylactic surgical fixation of the left femur and received post-operative RT encompassing the entire surgical nail (30 Gy/10 fractions) and palliative RT to the lumbar spine for pain relief (20 Gy/5 fractions). During cycle 4, palbociclib was stopped 3 days prior to the start of RT to reduce the risk of toxicity risk. However, 16 days after starting RT, she developed painful erythematous papules and bullae with moist desquamation on the left groin and lumbar spine.

MANAGEMENT & OUTCOME: Her symptoms were managed with topical Aquaphor-lidocaine, silver sulfadiazine, and aluminum acetate soaks. Dermatitis subsided to dry desquamation within 2 weeks. The patient denied late toxicity at 11 months follow-up.

DISCUSSION: Larger retrospective or prospective studies are needed to further elucidate the safety of combined CDK4/6 inhibitors and RT. In the meantime, special precautions are warranted in patients receiving combined therapy.}, } @article {pmid35924707, year = {2022}, author = {Kamido, S and Kakuta, Y and Fukuhara, S and Fujita, K and Uemura, M and Kiuchi, H and Imamura, R and Miyagawa, Y and Nonomura, N}, title = {[A Rare Case of Adrenal Metastasis Diagnosed before Discovery of Invasive Ductal Breast Cancer which was Confirmed to Be the Primary Site].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {68}, number = {7}, pages = {239-243}, doi = {10.14989/ActaUrolJap_68_7_239}, pmid = {35924707}, issn = {0018-1994}, mesh = {*Adrenal Gland Neoplasms/diagnostic imaging/surgery ; Adrenalectomy ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {A 54-year-old female underwent open left adrenalectomy for a left adrenal tumor in 2013. The pathology showed metastatic poorly differentiated adenocarcinoma. Despite a close examination, the primary tumor could not be identified. During the follow-up, a computed tomographic scan showed a hyper vascular tumor in the left breast in2015. A left mastectomy was performed for diagnosis and treatment. The pathology showed invasive ductal carcinoma of the breast. Comparing the histopathology and immunohistochemistry of the breast tumor with the adrenal tumor, the adrenal tumor was finally confirmed as metastatic invasive ductal carcinoma. Adrenal gland metastasis from invasive ductal carcinoma is said to be extremely rare. To our knowledge, there have been no reports of cases in which metastatic invasive ductal carcinoma of the adrenal gland was found before the primary site. We report this case with some literature review.}, } @article {pmid35914749, year = {2022}, author = {Dang, X and Zhang, X and Gao, Y and Song, H}, title = {Assessment of Neoadjuvant Treatment Response Using Automated Breast Ultrasound in Breast Cancer.}, journal = {Journal of breast cancer}, volume = {25}, number = {4}, pages = {344-348}, pmid = {35914749}, issn = {1738-6756}, abstract = {Breast imaging techniques are used to assess the tumor response to neoadjuvant treatment (NAT), which is increasingly one of the preferred therapeutic options and increases the rate of breast conservation for breast cancer. Herein, we report a case in which a woman was diagnosed with invasive ductal carcinoma in the left breast and received NAT before surgery. Automated breast ultrasound (AB US) was regularly performed before and during the NAT to evaluate the tumor response to NAT by measuring diameter changes and volume reductions of the tumor. Images showed that the tumor size was significantly reduced and disappeared after 7 cycles of NAT, except for macrocalcification. Postoperative histopathological examination confirmed that there were no residual tumor cells. We found that AB US overcame the limitations of handheld US, such as operator dependence, poor reproducibility and limited field of view, and can be an alternative modality to assess the tumor response of NAT in the absence of magnetic resonance imaging (MRI) instruments.}, } @article {pmid35914650, year = {2022}, author = {Petrus, P and Cervantes, M and Samad, M and Sato, T and Chao, A and Sato, S and Koronowski, KB and Park, G and Alam, Y and Mejhert, N and Seldin, MM and Monroy Kuhn, JM and Dyar, KA and Lutter, D and Baldi, P and Kaiser, P and Jang, C and Sassone-Corsi, P}, title = {Tryptophan metabolism is a physiological integrator regulating circadian rhythms.}, journal = {Molecular metabolism}, volume = {64}, number = {}, pages = {101556}, pmid = {35914650}, issn = {2212-8778}, support = {P30 CA062203/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Circadian Clocks ; *Circadian Rhythm/physiology ; Liver/metabolism ; Mammals ; Mice ; Suprachiasmatic Nucleus/metabolism ; Tryptophan/metabolism ; }, abstract = {OBJECTIVE: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.

METHODS: Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.

RESULTS: Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.

CONCLUSIONS: Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.}, } @article {pmid35910358, year = {2022}, author = {Xu, C and Liang, T and Liu, J and Fu, Y}, title = {RAB39B as a Chemosensitivity-Related Biomarker for Diffuse Large B-Cell Lymphoma.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {931501}, pmid = {35910358}, issn = {1663-9812}, abstract = {Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis. Methods: RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein-protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database. Results: RAB39B was highly expressed in multiple tumors including DLBCL. The protein-protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4[+] T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. In vitro experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells. Conclusion: RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.}, } @article {pmid35910265, year = {2022}, author = {Zhuang, J and Mei, H and Fang, F and Ma, X}, title = {What Is New in Classification, Diagnosis and Management of Chronic Musculoskeletal Pain: A Narrative Review.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {3}, number = {}, pages = {937004}, pmid = {35910265}, issn = {2673-561X}, abstract = {Chronic musculoskeletal pain (CMP) is the most common type of chronic pain, defined as persistent or recurrent pain condition deriving from musculoskeletal structures such as muscles, joints or bones that lasts for more than 3 months. CMP is multifactorial and severely affects people's quality of life. CMP may be influenced by a number of factors, including contextual factors, the presence of comorbidities, arthritis coping efficacy and access to CMP care. To deepen the comprehensive understanding of CMP, this narrative review provides the latest literature on disease classification, clinical diagnosis, treatment and basic research. In terms of the classification of the disease, here we introduce the 11th edition of the International Classification of Diseases (IDC-11), in which CMP is divided into chronic primary musculoskeletal pain and chronic secondary musculoskeletal pain. In the clinical diagnosis section, the progress of central sensitization in the diagnosis of CMP will also be summarized. In addition, we summarize some recent advances in clinical treatment and basic research.}, } @article {pmid35909232, year = {2023}, author = {Yang, ZJ and Liu, YX and Huang, Y and Chen, ZJ and Zhang, HZ and Yu, Y and Wang, X and Cao, XC}, title = {The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {2493-2504}, pmid = {35909232}, issn = {2045-7634}, mesh = {Humans ; Female ; Ki-67 Antigen/metabolism ; *Receptor, ErbB-2/metabolism ; Retrospective Studies ; *Breast Neoplasms/pathology ; Disease-Free Survival ; Receptors, Progesterone/metabolism ; Biomarkers, Tumor/metabolism ; Prognosis ; }, abstract = {BACKGROUND: Breast cancer (BC) remains the leading cause of cancer-related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed.

METHODS: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2-negative breast invasive ductal carcinoma. According to the expression level of PR and Ki-67 index, the Luminal B (HER2-negative) BCs were divided into three groups: ER+PR-Ki67low (ER-positive, PR-negative, and Ki-67 index <20%), ER+PR+Ki67high (ER-positive, PR-positive, and Ki-67 index ≥20%), and ER+PR-Ki67high (ER-positive, PR-negative, and Ki-67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log-rank χ[2] value.

RESULTS: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease-free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR-Ki67high subgroup have the worst survival outcome in Luminal B (HER2-negative) subtype, similar to Triple-negative patients. Besides, the ER+PR+Ki67high has worse 5-year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR-Ki67high subtype were more likely to have high RI for distance recurrence (RI-DR) and local recurrence (RI-LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2-negative) BC patients, which may help in clinical decision-making for individual treatment.}, } @article {pmid35909017, year = {2022}, author = {Rao, RA and Kozaily, E and Jawaid, O and Sabra, M and El-Am, EA and Chaaya, RGB and Woiewodski, L and Elsemesmani, H and Ramchandani, J and Shah, C and Guglin, M and Das, MK}, title = {Comparison of and Frequency of Mortality, Left Ventricular Assist Device Implantation, Ventricular Arrhythmias, and Heart Transplantation in Patients With Familial Versus Nonfamilial Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {179}, number = {}, pages = {83-89}, doi = {10.1016/j.amjcard.2022.06.018}, pmid = {35909017}, issn = {1879-1913}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac ; *Cardiomyopathy, Dilated ; *Heart Transplantation ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Stroke Volume ; Ventricular Remodeling ; }, abstract = {We postulated that familial idiopathic dilated cardiomyopathy (F-IDC) is associated with a worse prognosis than nonfamilial IDC (nonF-IDC). Patients with F-IDC had either a strong family history and/or proved genetic mutations. We studied long-term prognosis (mean follow-up: 6.1 ± 4.1 years) of 162 patients with IDC (age: 55.5 ± 17.9 years, men: 57.8%, 50% F-IDC) with an implantable cardioverter-defibrillator or cardiac resynchronization therapy. The primary end point was a composite of death, left ventricular (LV) assist device implant, or heart transplantation. The secondary end point was a ventricular arrhythmia event. There was no significant difference in the prevalence of diabetes, hypertension, New York Heart Association class, medical therapy, and years of follow-up between the F-IDC and nonF-IDC groups. Patients with F-IDC were younger than patients with nonF-IDC (49.1 ± 17.0 years vs 61.6 ± 16.5 years, p <0.001). Mean LV ejection fraction was significantly lower in F-IDC group than in the nonF-IDC group (26 ± 12% vs 31 ± 12%, p = 0.022). The primary end point was achieved in 54 patients in F-IDC group (66.7%) versus 19 in the nonF-IDC group (23.5%) (p <0.001). The Kaplan-Meier survival estimates for the composite end point and for ventricular arrhythmia were significantly lower in the F-IDC versus nonF-IDC (log-rank p ≤0.001 and 0.04, respectively). F-IDC was the only multivariable predictor of the primary composite end point (hazard ratio 3.419 [95% confidence interval 1.845 to 6.334], p <0.001). The likelihood of LV remodeling manifested by LV ejection fraction improvement (≥10%) was significantly lower in F-IDC than nonF-IDC (27.1% vs 44.8%, p = 0.042). In conclusion, F-IDC is a predictor of mortality, need for LV assist device, or heart transplantation. F-IDC is associated with significantly lower event-free survival for primary end point and ventricular arrhythmia than nonF-IDC. F-IDC has significantly lower likelihood of LV reverse remodeling than nonF-IDC.}, } @article {pmid35908296, year = {2022}, author = {Cerea, S and Doron, G and Manoli, T and Patania, F and Bottesi, G and Ghisi, M}, title = {Cognitive training via a mobile application to reduce some forms of body dissatisfaction in young females at high-risk for body image disorders: A randomized controlled trial.}, journal = {Body image}, volume = {42}, number = {}, pages = {297-306}, doi = {10.1016/j.bodyim.2022.07.010}, pmid = {35908296}, issn = {1873-6807}, mesh = {*Body Dissatisfaction ; *Body Dysmorphic Disorders/diagnosis/psychology/therapy ; Body Image/psychology ; Cognition ; *Feeding and Eating Disorders/prevention & control ; Female ; Humans ; *Mobile Applications ; }, abstract = {Body dissatisfaction has been related to Body Image Disorders (BIDs) such as Eating Disorders (EDs) and Body Dysmorphic Disorder (BDD). This study investigates the efficacy of a mHealth app in reducing body dissatisfaction, BDD/ED symptoms and related features. Ninety-five women who were identified as high-risk of developing BIDs (using the Structured Clinical Interview for DSM-5) were randomized into: immediate-use App (iApp group; n = 47) and delayed-use App (dApp group; n = 48). The iApp group started using the app at baseline for 16 days (T1). The dApp group started using the app at T1 for 16 days. Participants completed questionnaires at baseline (T0), 16 days from baseline (T1), and 32 days from baseline (T2). Repeated measure Multivariate Analysis of Variance (MANOVA) showed Group (iApp vs. dApp) × Time (T0 vs. T1) interactions indicating decrease in BDD symptoms and body dissatisfaction related to EDs in the iApp group at T1. The Reliable Change Index indicated changes on extreme body dissatisfaction/BDD symptoms for 34.74% of participants. Although preliminary, these findings highlight that a mHeatlh app might reduce BDD symptoms and body dissatisfaction related to EDs in women at high-risk for BIDs. Effects on ED symptoms and associated features seem more limited.}, } @article {pmid35907957, year = {2022}, author = {Oehler, D and Spychala, A and Gödecke, A and Lang, A and Gerdes, N and Ruas, J and Kelm, M and Szendroedi, J and Westenfeld, R}, title = {Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {169}, pmid = {35907957}, issn = {1741-7007}, mesh = {Alternative Splicing ; Animals ; Humans ; Mice ; *Myocardial Ischemia/genetics ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; Protein Isoforms/genetics ; RNA, Messenger/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction.

RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice.

CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.}, } @article {pmid35906698, year = {2022}, author = {Lee, S and Osmanbeyoglu, HU}, title = {Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.}, journal = {Breast cancer research : BCR}, volume = {24}, number = {1}, pages = {54}, pmid = {35906698}, issn = {1465-542X}, support = {R00 CA207871/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Chromatin/genetics ; Female ; Humans ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored.

METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset.

RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC.

CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.}, } @article {pmid35904971, year = {2022}, author = {Wan, M and Song, S and Feng, W and Shen, H and Luo, Y and Wu, W and Shen, J}, title = {Metal-Organic Framework (UiO-66)-Based Temperature-Responsive Pesticide Delivery System for Controlled Release and Enhanced Insecticidal Performance against Spodoptera frugiperda.}, journal = {ACS applied bio materials}, volume = {5}, number = {8}, pages = {4020-4027}, doi = {10.1021/acsabm.2c00549}, pmid = {35904971}, issn = {2576-6422}, mesh = {Animals ; Delayed-Action Preparations/pharmacology ; *Insecticides/pharmacology ; *Metal-Organic Frameworks ; *Pesticides/pharmacology ; Phthalic Acids ; Spodoptera ; Temperature ; }, abstract = {Spodoptera frugiperda is a global pest that brings about great disasters to crops. Conventional pesticide formulations often suffer from poor water solubility, low stability, burst release, weak leaf adhesion, and low efficiency. To improve the insecticidal activity of pesticides, a stimuli-responsive controlled release pesticide delivery system (PDS) has attracted extensive attention in recent years. This paper reports a temperature-responsive controlled release PDS based on poly(N-isopropyl acrylamide) (PNIPAm)-modified indoxacarb (IDC)-loaded UiO-66-(COOH)2 (IDC@UiO-66-(COOH)2-PNIPAm) and studies its insecticidal activities against S. frugiperda. The UiO-66-(COOH)2 nanocarrier has an excellent pesticide loading performance, and the loading rate for IDC is 78.69%. The as-prepared PDS has good stability, temperature-responsive controllable release performance, and enhanced leaf affinity, so it can effectively improve the utilization rate of IDC. The insecticidal experiment indicates that the PDS has an enhanced control effect against S. frugiperda. In addition, biosafety analysis further verifies that the PDS exhibits no obvious negative effects on the germination of maize seeds and the growth of maize seedlings. In view of this, we believe that this PDS will have a broad application in the field of pesticide formulation innovation, pest management, and sustainable agricultural development.}, } @article {pmid35903710, year = {2022}, author = {Bhimani, F and Johnson, K and Brodin, NP and Tomé, WA and Fox, J and Mehta, K and McEvoy, M and Feldman, S}, title = {Case Report: Can Targeted Intraoperative Radiotherapy in Patients With Breast Cancer and Pacemakers be the New Standard of Care?.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {927174}, pmid = {35903710}, issn = {2234-943X}, abstract = {BACKGROUND: Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker.

CASE REPORTS: Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 - invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT.

CONCLUSION: Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.}, } @article {pmid35900825, year = {2022}, author = {Nitsan, G and Baharav, S and Tal-Shir, D and Shakuf, V and Ben-David, BM}, title = {Speech Processing as a Far-Transfer Gauge of Serious Games for Cognitive Training in Aging: Randomized Controlled Trial of Web-Based Effectivate Training.}, journal = {JMIR serious games}, volume = {10}, number = {3}, pages = {e32297}, pmid = {35900825}, issn = {2291-9279}, abstract = {BACKGROUND: The number of serious games for cognitive training in aging (SGCTAs) is proliferating in the market and attempting to combat one of the most feared aspects of aging-cognitive decline. However, the efficacy of many SGCTAs is still questionable. Even the measures used to validate SGCTAs are up for debate, with most studies using cognitive measures that gauge improvement in trained tasks, also known as near transfer. This study takes a different approach, testing the efficacy of the SGCTA-Effectivate-in generating tangible far-transfer improvements in a nontrained task-the Eye tracking of Word Identification in Noise Under Memory Increased Load (E-WINDMIL)-which tests speech processing in adverse conditions.

OBJECTIVE: This study aimed to validate the use of a real-time measure of speech processing as a gauge of the far-transfer efficacy of an SGCTA designed to train executive functions.

METHODS: In a randomized controlled trial that included 40 participants, we tested 20 (50%) older adults before and after self-administering the SGCTA Effectivate training and compared their performance with that of the control group of 20 (50%) older adults. The E-WINDMIL eye-tracking task was administered to all participants by blinded experimenters in 2 sessions separated by 2 to 8 weeks.

RESULTS: Specifically, we tested the change between sessions in the efficiency of segregating the spoken target word from its sound-sharing alternative, as the word unfolds in time. We found that training with the SGCTA Effectivate improved both early and late speech processing in adverse conditions, with higher discrimination scores in the training group than in the control group (early processing: F1,38=7.371; P=.01; ηp[2]=0.162 and late processing: F1,38=9.003; P=.005; ηp[2]=0.192).

CONCLUSIONS: This study found the E-WINDMIL measure of speech processing to be a valid gauge for the far-transfer effects of executive function training. As the SGCTA Effectivate does not train any auditory task or language processing, our results provide preliminary support for the ability of Effectivate to create a generalized cognitive improvement. Given the crucial role of speech processing in healthy and successful aging, we encourage researchers and developers to use speech processing measures, the E-WINDMIL in particular, to gauge the efficacy of SGCTAs. We advocate for increased industry-wide adoption of far-transfer metrics to gauge SGCTAs.}, } @article {pmid35900570, year = {2022}, author = {Bansal, VY and Bansal, VV and Shah, SV and Bellige, AR}, title = {Primary ectopic breast carcinoma arising in the inguinal region in a male patient.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {3}, pages = {837-839}, doi = {10.4103/jcrt.JCRT_777_20}, pmid = {35900570}, issn = {1998-4138}, mesh = {Aged ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/therapy ; Humans ; Male ; Neoplasm, Residual ; Tamoxifen/therapeutic use ; }, abstract = {Carcinoma arising in ectopic breast tissue is a rare entity, especially in males, in whom the diagnosis is often delayed due to a low index of suspicion. Conventional imaging techniques fail to characterize the tumor, adding further to the diagnostic dilemma. We report the first case in our knowledge of an extramammary primary breast carcinoma arising in the inguinal region in a male. Our patient, a 69-year-old male, presented with a swelling in the left inguinal region, which was excised and diagnosed as luminal A type invasive ductal carcinoma. He received adjuvant external beam radiotherapy (50 Gy administered in 25 fractions) and tamoxifen. A follow-up examination performed 6 months after the completion of the last dose of radiotherapy showed no residual disease. The modalities of treatment for such tumors have been discussed, with emphasis on surgery and radiotherapy, given the aggressive nature of the disease.}, } @article {pmid35899956, year = {2023}, author = {Shi, J and Chen, L and Wang, B and Zhang, H and Xu, L and Ye, J and Liu, Y and Shao, Y and Sun, X and Zou, Y}, title = {Diagnostic Value of Ultrasound Elastography in the Differentiation of Breast Invasive Ductal Carcinoma and Ductal Carcinoma In situ.}, journal = {Current medical imaging}, volume = {19}, number = {3}, pages = {286-291}, doi = {10.2174/1573405618666220721091940}, pmid = {35899956}, issn = {1573-4056}, mesh = {Female ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Elasticity Imaging Techniques ; Breast/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Ultrasound elastography (US-E) has been shown superior to the conventional US in diagnosing benign and malignant breast lesions. In contrast, the role of US-E in the differentiation of breast invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) has been poorly described.

OBJECTIVE: This study was designed to examine the diagnostic value of US-E in the differentiation of IDC and DCIS.

METHODS: Medical records of all patients who underwent preoperative US-E evaluation and were diagnosed with IDC or DCIS at our hospital from April-December 2019 were retrieved and analyzed. Those who had prior surgical treatment, chemotherapy or radiotherapy were excluded.

RESULTS: Twenty women with DCIS and 111 women with IDC were included in this study. There were no significant differences in age, maximum lesion diameter and tumor volume between the two groups. While shear wave velocity (SWV) inside the lesion and in the surrounding tissue, strain ratio and tumor area ratio were not substantially different between the two groups, SWV at the edge of the lesion was significantly higher in IDC cases, which had an AUC value of 0.66 with a sensitivity of 65.8% and a specificity of 60.0% for the differential diagnosis of IDC and DCIS.

CONCLUSION: Edge SWV is significantly higher in IDC than that in DCIS, which had a moderate diagnostic value for the differentiation of IDC and DCIS, similar to the performance of diffusion-weighted magnetic resonance imaging as reported in the literature. In terms of cost-effectiveness, US-E could be very useful while waiting for further evaluations to determine whether US-E combined with other diagnostic modalities improves the diagnostic performance.}, } @article {pmid35898837, year = {2023}, author = {Suzuki, Y and Hoshi, K and Tominaga, K and Inaba, Y and Yoshinaga, T and Kojimahara, S and Maki, R and Nemoto, R and Tetsuka, Y and Kawata, Y and Yamamiya, A and Sugaya, T and Iso, Y and Takada-Owada, A and Ishida, K and Goda, K and Irisawa, A}, title = {A case of obstructive jaundice caused by metastasis of breast cancer to the intra/extrahepatic bile duct.}, journal = {DEN open}, volume = {3}, number = {1}, pages = {e144}, pmid = {35898837}, issn = {2692-4609}, abstract = {A 38-year-old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.}, } @article {pmid35893780, year = {2022}, author = {Jolivet, L and Ait Mohamed Amar, I and Horiot, C and Boursin, F and Colas, C and Letast, S and Denevault-Sabourin, C and Allard-Vannier, E and Joubert, N and Aubrey, N}, title = {Intra-Domain Cysteines (IDC), a New Strategy for the Development of Original Antibody Fragment-Drug Conjugates (FDCs).}, journal = {Pharmaceutics}, volume = {14}, number = {8}, pages = {}, pmid = {35893780}, issn = {1999-4923}, abstract = {Antibody-drug conjugates (ADCs) derived from a full immunoglobulin-G (IgG) are associated with suboptimal solid-tumor penetration and Fc-mediated toxicities. Antibody fragment-drug conjugates (FDCs) could be an alternative. Nevertheless, innovative solutions are needed to implant cysteines as conjugation sites in the single-chain fragment variable (scFv) format, which is the backbone from which many other antibody formats are built. In addition, the bioconjugation site has the utmost importance to optimize the safety and efficacy of bioconjugates. Our previous intra-tag cysteine (ITC) strategy consisted of introducing a bioconjugation motif at the C-terminal position of the 4D5.2 scFv, but this motif was subjected to proteolysis when the scFv was produced in CHO cells. Considering these data, using three intra-domain cysteine (IDC) strategies, several parameters were studied to assess the impact of different locations of a site-specific bioconjugation motif in the variable domains of an anti-HER2 scFv. In comparison to the ITC strategy, our new IDC strategy allowed us to identify new fragment-drug conjugates (FDCs) devoid of proteolysis and exhibiting enhanced stability profiles, better affinity, and better ability to kill selectively HER2-positive SK-BR-3 cells in vitro at picomolar concentrations. Thus, this work represents an important optimization step in the design of more complex and effective conjugates.}, } @article {pmid35892151, year = {2022}, author = {Lee, WP and Shetty, SS and Seah, CMJ and Tan, PT and Tan, SM}, title = {Does concomitant ductal carcinoma in situ affect the clinical outcome in breast cancer patients with invasive ductal carcinoma: An Asian perspective.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {5}, number = {9}, pages = {e1646}, pmid = {35892151}, issn = {2573-8348}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology/therapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology/therapy ; Disease Progression ; Female ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is an established precursor to invasive ductal carcinoma (IDC) and its coexistence with IDC appear to favor reduced biological aggressiveness. Its prognostic implication and ability to affect clinical outcome has been understudied in Asia. This study aims to explore if concomitant DCIS affects the clinical behavior and outcomes among Asians.

AIM: Stages I to III breast cancer patients with histological proven IDC, diagnosed and treated in a single institution from June 1, 2004 to June 30, 2014 were included in this study. Statistical analyses were conducted using Χ[2] test, independent t test, multivariate logistic regression and Kaplan-Meier test.

METHODS AND RESULTS: A total of 818 patients were identified, including 224 and 594 patients with isolated IDC (No-DCIS) and IDC with coexisting DCIS (IDC-DCIS) respectively. Patients with IDC-DCIS were found to have smaller tumors (median: 22 mm, p ≤ .01), estrogen receptor positivity (p = .001), progesterone receptor positivity (p < .001) and associated with better pathological stage (p = .001). Patients with No-DCIS were 1.6 times more likely to develop disease progression (95% CI: 1.1-2.3, p = .027) and subsequently associated with distant recurrences (20.5% vs. 13.6%, p = .02). The breast cancer specific 5 year overall survival rate for patients with No-DCIS and those with IDC-DCIS was 90.9% (95% CI: 86.2%-94.5%) and 93.7% (95% CI: 91.4%-95.5%), respectively (p = .202).

CONCLUSION: The presence of DCIS component in IDC among Asians is associated with favorable tumor biological profile, thereby indicating reduced disease aggressiveness. Our study is the first to report the clinical significance in terms of disease progression and distant recurrences among Asians.}, } @article {pmid35891814, year = {2022}, author = {Javed, A and Medina, Y and Bux, A and Sahra, S and Rojas-Marte, G}, title = {Rare Case of Reversible Pulmonary Arterial Hypertension Secondary to Cyclophosphamide and Doxorubicin Chemotherapy.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e26207}, pmid = {35891814}, issn = {2168-8184}, abstract = {Pulmonary arterial hypertension (PAH), characterized as a resting mean pulmonary artery pressure greater than 25 mmHg, is due to the narrowing of the pulmonary arteries, which can be idiopathic, inherited, or drug-related. Alkylating agents, including cyclophosphamide, are a risk factor for developing the pulmonary veno-occlusive disease. Drug-induced PAH is extremely rare. A 59-year-old female with newly diagnosed invasive ductal carcinoma of the right breast and high-grade ductal carcinoma in situ of the left breast was initiated treatment with doxorubicin and cyclophosphamide. About one week after receiving the first cycle, the patient developed worsening lower extremity edema and shortness of breath. She was then hospitalized, and a transthoracic echocardiogram and coronary angiogram revealed PAH. The team then changed the breast cancer treatment regimen to Taxol and carboplatin, and PAH was resolved in a follow-up echocardiogram after five months. This report has described the first case of PAH directly related to cyclophosphamide and doxorubicin. It is imperative to promptly recognize this rare but important side-effect as early diagnosis and response can potentially reverse the disease progression.}, } @article {pmid35890415, year = {2022}, author = {Deguchi, S and Kadowaki, R and Otake, H and Taga, A and Nakazawa, Y and Misra, M and Yamamoto, N and Sasaki, H and Nagai, N}, title = {Combination of Lanosterol and Nilvadipine Nanosuspensions Rescues Lens Opacification in Selenite-Induced Cataractic Rats.}, journal = {Pharmaceutics}, volume = {14}, number = {7}, pages = {}, pmid = {35890415}, issn = {1999-4923}, support = {21K06656//The Ministry of Education, Culture, Sports, Science, and Technology of Japan/ ; }, abstract = {It has recently been reported that lanosterol (LAN) plays a preventive role against lens opacification through the reversal of crystalline aggregation. However, the effect of LAN is not sufficient to restore lens transparency. In this study, we designed ophthalmic nanosuspensions (LAN-ONSs and NIL-ONSs) based on LAN and nilvadipine (NIL), which can counteract cataract-related factors (e.g., enhanced Ca[2+] and calpain levels), and investigated whether the combination of LAN-ONSs and NIL-ONSs can restore the nuclear lens opacity in sodium-selenite-induced cataractic rats (cataractic rats). The mean particle sizes of the LAN-ONSs and NIL-ONSs were 108.8 nm and 89.0 nm, respectively. The instillation of the LAN-ONSs or NIL-ONSs successfully delivered the drugs (LAN or NIL) into the lenses of the rats, although the instillation of LAN-ONSs or NIL-ONSs alone did not increase lens transparency in the cataractic rats. On the other hand, the cataract-related factors (enhanced Ca[2+] and calpain levels) were significantly alleviated by the combination of LAN-ONSs and NIL-ONSs; furthermore, the perinuclear refractile ring in the lens nucleus and enhanced number of swollen fibers were attenuated by the LAN-ONS and NIL-ONS combination. Moreover, the opacity levels in the cataractic rats were reduced after treatment with the combination of LAN-ONSs and NIL-ONSs. It is possible that the combination of LAN and NIL will be useful for the treatment of lens opacification in the future.}, } @article {pmid35884039, year = {2022}, author = {Aggius-Vella, E and Gori, M and Campus, C and Petri, S and Tinelli, F}, title = {Motor Influence in Developing Auditory Spatial Cognition in Hemiplegic Children with and without Visual Field Disorder.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35884039}, issn = {2227-9067}, support = {9848349//European Union/ ; RC Finalizzata 2021 and 5x1000 volountary contribution//Governo Italiano/ ; }, abstract = {Spatial representation is a crucial skill for everyday interaction with the environment. Different factors seem to influence spatial perception, such as body movements and vision. However, it is still unknown if motor impairment affects the building of simple spatial perception. To investigate this point, we tested hemiplegic children with (HV) and without visual field (H) disorders in an auditory and visual-spatial localization and pitch discrimination task. Fifteen hemiplegic children (nine H and six HV) and twenty with typical development took part in the experiment. The tasks consisted in listening to a sound coming from a series of speakers positioned at the front or back of the subject. In one condition, subjects were asked to discriminate the pitch, while in the other, subjects had to localize the position of the sound. We also replicated the spatial task in a visual modality. Both groups of hemiplegic children performed worse in the auditory spatial localization task compared with the control, while no difference was found in the pitch discrimination task. For the visual-spatial localization task, only HV children differed from the two other groups. These results suggest that movement is important for the development of auditory spatial representation.}, } @article {pmid35880762, year = {2022}, author = {Billeter, AT and Scheurlen, KM and Israel, B and Straub, BK and Schirmacher, P and Kopf, S and Nawroth, PP and Müller-Stich, BP}, title = {Gastric Bypass Resolves Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Low-BMI Patients: A Prospective Cohort Study.}, journal = {Annals of surgery}, volume = {276}, number = {5}, pages = {814-821}, pmid = {35880762}, issn = {1528-1140}, mesh = {Adipokines ; Adolescent ; Adult ; Aged ; Blood Glucose/metabolism ; Body Mass Index ; C-Peptide ; *Diabetes Mellitus, Type 2/complications ; *Gastric Bypass ; *Gastrointestinal Hormones/metabolism ; Glucagon ; Glycated Hemoglobin/metabolism ; Humans ; Insulin ; *Liver Diseases/complications ; Middle Aged ; *Obesity, Morbid/complications/metabolism/surgery ; Prospective Studies ; Sirtuin 1 ; Young Adult ; }, abstract = {OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.

METHODS: Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.

RESULTS: MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.

CONCLUSIONS: RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.}, } @article {pmid35880695, year = {2023}, author = {Zhang, J and Lin, H and Hou, L and Xiao, H and Gong, X and Guo, X and Cao, X and Liu, Z}, title = {Exploration of the breast ductal carcinoma in situ signature and its prognostic implications.}, journal = {Cancer medicine}, volume = {12}, number = {3}, pages = {3758-3772}, pmid = {35880695}, issn = {2045-7634}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Prospective Studies ; *Breast Neoplasms/pathology ; Kaplan-Meier Estimate ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Protein Serine-Threonine Kinases ; NIMA-Related Kinases ; }, abstract = {Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.}, } @article {pmid35879144, year = {2023}, author = {Song, YQ and Hong, J and Wang, JY and Peng, J and Han, JH and Luo, HL}, title = {Dosimetric comparison of different intensity-modulated radiotherapy techniques for whole-breast irradiation of right-breast cancer.}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {27}, number = {1}, pages = {11-16}, doi = {10.1016/j.canrad.2022.04.009}, pmid = {35879144}, issn = {1769-6658}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/surgery ; *Radiotherapy, Intensity-Modulated/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Breast ; Radiometry ; Radiotherapy Dosage ; Organs at Risk/radiation effects ; }, abstract = {PURPOSE: This study compared the dosimetric parameters of field-in-field forward intensity-modulated radiotherapy (FIF-IMRT) and fixed-field inversely optimized intensity-modulated radiotherapy (FFIO-IMRT) for the whole-breast irradiation of patients undergoing right-breast lumpectomy.

MATERIAL AND METHODS: A total of 30 patients with pT1-2N0M0 right-breast invasive ductal carcinoma were enrolled in this study. Two different treatment plans, i.e., FIF-IMRT and FFIO-IMRT, were designed for each patient. The dosimetric parameters of the two treatment plans were compared including ipsilateral lung and heart, conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV).

RESULTS: Fixed-field inversely optimized intensity-modulated radiotherapy was found to significantly improve CI (83.302% vs. 60.146%) and HI (11.837% vs. 19.280%), and significantly reduced V25 (18.038% vs. 19.653%) and V30 (15.790% vs. 18.492%) of the ipsilateral lung. It also significantly increased V5 (69.791% vs. 32.615%) of the ipsilateral lung and V5 (61.579% vs. 3.829%), V10 (14.130% vs. 0.381%), V20 (1.843% vs. 0.051%), and Dmean (5.211Gy vs. 1.870Gy) of the heart.

CONCLUSION: Regardless of improving the conformity and homogeneity of PTV and reducing the ipsilateral lung irradiation volume at high doses, FFIO-IMRT significantly raised the ipsilateral lung irradiated volume at low doses, as well as the irradiation volume and mean radiation doses to the heart. This limits its use in patients with early-stage right breast cancer.}, } @article {pmid35875050, year = {2022}, author = {Liu, WC and Li, MX and Wu, SN and Tong, WL and Li, AA and Sun, BL and Liu, ZL and Liu, JM}, title = {Using Machine Learning Methods to Predict Bone Metastases in Breast Infiltrating Ductal Carcinoma Patients.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {922510}, pmid = {35875050}, issn = {2296-2565}, mesh = {Bayes Theorem ; *Breast Neoplasms ; *Carcinoma, Ductal ; Female ; Humans ; Machine Learning ; Quality of Life ; }, abstract = {Breast cancer (BC) was the most common malignant tumor in women, and breast infiltrating ductal carcinoma (IDC) accounted for about 80% of all BC cases. BC patients who had bone metastases (BM) were more likely to have poor prognosis and bad quality of life, and earlier attention to patients at a high risk of BM was important. This study aimed to develop a predictive model based on machine learning to predict risk of BM in patients with IDC. Six different machine learning algorithms, including Logistic regression (LR), Naive Bayes classifiers (NBC), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), and Extreme gradient boosting (XGB), were used to build prediction models. The XGB model offered the best predictive performance among these 6 models in internal and external validation sets (AUC: 0.888, accuracy: 0.803, sensitivity: 0.801, and specificity: 0.837). Finally, an XGB model-based web predictor was developed to predict risk of BM in IDC patients, which may help physicians make personalized clinical decisions and treatment plans for IDC patients.}, } @article {pmid35873268, year = {2022}, author = {Cohen, R and Slobodin, O}, title = {An Authentic Inner Compass and Need Satisfaction as Wellbeing Resources in Bedouin Teaching Students During the COVID-19.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {870764}, pmid = {35873268}, issn = {1664-0640}, abstract = {A growing body of literature suggests that students from underserved backgrounds are more vulnerable to the adverse economic, emotional, and academic effects of the current COVID-19 pandemic. While this vulnerability was attributed to multiple structural and socio-cultural barriers, little attention has been paid to the role of psychological resources in preserving wellbeing in times of crisis and change. Guided by the Self-Determination Theory (SDT), the current study examined the role of the authentic inner compass (AIC) and need-satisfaction in predicting the wellbeing of Bedouin students attending teachers' higher education institutes in the south of Israel during the COVID-19. Participants were 84 Bedouin teaching students (84.1% female) who completed online questionnaires addressing the sense of AIC, need-based experiences, psychological distress, and positive affect. Consistent with the propositions of the SDT, we found that a strong and clear sense of AIC, as well as high need satisfaction and low need frustration, were associated with lower distress and higher positive effect in Bedouin teaching students. We have also found that need satisfaction moderated the effect of the AIC on students' wellbeing so that AIC better predicted lower distress and higher positive effect when students' levels of need satisfaction were higher. Our findings lend further support to the importance of the AIC and need satisfaction to optimal functioning even in collectivist cultural contexts that do not prioritize values of autonomy. The current study provides insight into the interplay between AIC and need-based experience by describing the conditions under which AIC may be beneficial for wellbeing in times of crisis.}, } @article {pmid35869577, year = {2022}, author = {Chen, Z and Salibay, C and Elatre, W and Naritoku, WY and Ma, Y and Martin, SE and Wang, T}, title = {Performance of breast fine needle aspiration as an initial diagnostic tool: A large academic hospital experience.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {33}, number = {6}, pages = {707-715}, pmid = {35869577}, issn = {1365-2303}, mesh = {Biopsy, Fine-Needle ; Breast/abnormalities ; *Breast Neoplasms/diagnosis/pathology ; Female ; *Fibroadenoma/diagnosis ; Hospitals ; Humans ; Hypertrophy ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: The clinical performance of the Yokohama reporting system for breast cytology remains uncertain.

METHODS: In this study, we retrospectively evaluated 318 breast fine needle aspirations (FNABs) from Los Angeles County Hospital over a five-year period, analysing data for breast cytology, histology, and radiology.

RESULTS: Among 318 breast FNAB cases, 78.3% (249/318) were benign and 5.3% (17/318) malignant. Of 83 cases with follow-up histology, 14.5% (12/83) were insufficient, 66.3% (55/83) were benign, and 16.9% (17/83) were malignant. Of 55 benign cases, 61.8% (34/55) were fibroadenoma and 9 (9/55, 16.4%) were fibrocystic changes. Two cases were diagnosed as "atypical" but confirmed "benign" on core needle biopsy (CNB). No "suspicious" cases were found. Seventeen malignant cases were confirmed by CNB, including 70.6% (12/17) invasive ductal carcinoma, 11.8% (2/17) invasive lobular carcinoma, and one malignant phyllodes tumour. Receptor studies on cell blocks of three malignant cases showed concordant results with CNB results. In addition, 82.2% (148/180) of lesions with Breast Imaging-Reporting and Data System (BI-RADS) scores of 2 or 3 were benign and 92.3% (12/13) BI-RADS score 5 lesions were malignant on FNAB. Finally, 90% (67/74) of BI-RADS 4a lesions were benign, and 97% (36/37) of fibroadenomas were BI-RADS score 4a.

CONCLUSION: This, by far the largest U.S. breast cytology study, showed 93.3% sensitivity, 100% specificity, 100% positive predictive value, and 98.2% negative predictive value for breast FNAB. Women with breast lesions of BI-RADS score 3 or less have a low risk of malignancy; FNAB would contribute to the reduction of excisional biopsies. FNAB can be considered as an initial diagnostic tool for BI-RADS 4 mass/lesions and satellite lesions, as well as for triaging patients.}, } @article {pmid35868130, year = {2022}, author = {Ou, Q and Li, YD and Chen, J and Yuan, LL and Li, W}, title = {A Very rare case report of male invasive micropapillary breast carcinoma in China and review of literature.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107408}, pmid = {35868130}, issn = {2210-2612}, abstract = {INTRODUCTION: To report a rare case of male breast micropapillary carcinoma (MBMC) with early metastasis of axillary lymph nodes, the molecular characteristics were further studied in both primary and metastatic foci. In addition, we have reviewed similar published cases in the literature and tried to outline the molecular characteristics of this disease.

PRESENTATION OF CASE: A 63-year-old male patient presented with a painless mass on the medial side of left breast and was pathologically diagnosed with MBMC. Postoperative examination revealed 80 % invasive ductal carcinoma (IDC) and 20 % invasive micropapillary carcinoma (IMPC) in the mass, with a histological grade WHO III. There were 25 axillary lymph nodes, 11 of which were metastatic, including 5 macrometastasis and 1 micrometastasis, with a lymph node metastasis rate of 44 % (11/25). Pathological TNM stage: pT2N2M0. Immunohistochemical results in primary foci: AR (90 %, +), HER- 2 (1 +) and ER (90 %, +), PR (60 %, +), E - cadherin (+), EGFR (-), GATA - 3 (90 %, 3 +), Ki - 67 (50 %). Lymph node metastasis: AR (40 %, strong +), HER-2 (2+), ER (90 %, strong +), PR (40 %, strong +), Ki-67 (50 %). AR and Ki-67 were obviously expressed in both primary and metastatic foci. A mixture of IDC and IMPC was found in lymph node metastases, both of which expressed varying degrees of AR and Ki-67.

CLINICAL DISCUSSION: MBMC is easy to early metastasized to lymph node. In this case, there was no significant difference between primary and metastatic cancer in molecular results. It is positive for ER and PR, but negative for HER-2 in this patient. There is few data on male HER-2 expression, HER-2 expression is deficient in this case. AR is found to be positive in 50 % of MBMC cases, although their clinical relevance has not been established yet. The significance of EGFR in the prognosis of MBMC remains unclear, however, EGFR positive expression is not found in this patient.

CONCLUSIONS: MBMC is a rare disease characterized by early lymph node metastasis, high histological grade, positive ER and PR, and generally negative HER-2. The molecular biological characteristics and prognostic significance of MBMC need to be further studied in order to develop the optimal treatment strategy.}, } @article {pmid35866222, year = {2022}, author = {Khanam, R and Islam, S and Rahman, S and Ahmed, S and Islam, A and Hasan, T and Hasan, E and Chowdhury, NH and Roy, AD and Jaben, IA and Nehal, AA and Yoshida, S and Manu, AA and Raqib, R and McCollum, ED and Shahidullah, M and Jehan, F and Sazawal, S and Bahl, R and Baqui, AH}, title = {Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05030}, pmid = {35866222}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Antibodies, Viral ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Communicable Disease Control ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Seroepidemiologic Studies ; }, abstract = {BACKGROUND: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh.

METHODS: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models.

RESULTS: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16,  95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years.

CONCLUSIONS: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.}, } @article {pmid35864546, year = {2022}, author = {Zhu, S and Zhao, J and Nie, L and Yin, W and Zhang, Y and Zhao, F and Ni, Y and Zhang, X and Wang, Z and Dai, J and Liu, Z and Chen, J and Zeng, Y and Wang, Z and Sun, G and Liang, J and Zhao, X and Zhu, X and Tao, R and Yang, J and He, B and Chen, N and Shen, P and Zeng, H}, title = {Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {237}, pmid = {35864546}, issn = {1741-7015}, mesh = {*Adenocarcinoma/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Homologous Recombination/genetics ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort.

METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method.

RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort.

CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.}, } @article {pmid35863289, year = {2022}, author = {Angellotti, G and Tomasicchio, G and Montanaro, AE and Telgrafo, M and Mastropasqua, MG and Punzo, C}, title = {Osteoclast-like stromal giant cells in invasive ductal breast cancer: A case series.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107421}, pmid = {35863289}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast Cancer with osteoclast-like stromal giant cells (OLGCs) is a rare pattern of invasive non-special type ductal carcinoma. The OLGCs are specific type of macrophage and are likely distinct from true osteoclasts. The aim of this case series was to describe the characteristics of this invasive ductal carcinoma rare histotype.

PRESENTATION OF CASES: The authors present the cases of two young women that, during national screening, discovered with mammography X-ray a breast lump suspected for malignancy. The core needle biopsy confirmed the malignancy of both nodule and in one patient the histological analysis revealed pre-operative OLGCs. In both cases the sentinel lymph node biopsy was negative therefore a quadrantectomy without axillary lymphadenectomy was done. The definitive histopathological examination was positive for invasive ductal carcinoma with OLGCs and CD 68 marker positivity. After surgery, patients underwent adjuvant therapy and multidisciplinary follow-up.

DISCUSSION: The origin and mechanism for developing osteoclast-like giant cells is unknown. The OLGCs directly descend from the precursors of the monocyte-macrophage. The rarity of this entity often promotes a misleading diagnosis, with >50 % of erroneous diagnosis of benign lesion. The prognostic significance of OLGCs in breast cancer is controversial, however it doesn't seem to influence the axillary lymph nodes spread. The presence of preoperative OLGCs didn't modify our surgical and oncological approach.

CONCLUSION: Breast Cancer with OLGCs is a rare tumour that has a similar prognosis to other carcinomas of identical grade and stage in most cases. The rarity and characteristics of this neoplasm require personalized treatments, discussed by a multidisciplinary team.}, } @article {pmid35860832, year = {2022}, author = {Chang, PH and Lee, CH and Wu, TM and Yeh, KY and Wang, HM and Huang, WK and Chan, SC and Chou, WC and Kuan, FC and Kuo, HC and Kuo, YC and Hu, CC and Hsieh, JC}, title = {Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer.}, journal = {Therapeutic advances in medical oncology}, volume = {14}, number = {}, pages = {17588359221110182}, pmid = {35860832}, issn = {1758-8340}, abstract = {BACKGROUND: This study aimed to investigate the role of circulating tumor cells (CTCs) and circulating cancer stem-like cells (cCSCs) before and after one cycle of chemotherapy and assessed the effects of early changes in CTCs and cCSCs on the outcomes of patients with metastatic breast cancer.

METHODS: Patients with stage IV invasive ductal carcinoma of the breast who received first-line chemotherapy between April 2014 and January 2016 were enrolled. CTCs and cCSCs were measured before the first cycle of chemotherapy (baseline) and on day 21, before the second cycle of chemotherapy commenced; a negative selection strategy and flow cytometry protocol were employed.

RESULTS: CTC and cCSC counts declined in 68.8 and 45.5% of patients, respectively. Declines in CTCs and cCSCs following the first chemotherapy cycle were associated with superior chemotherapy responses, longer progression-free survival (PFS), and longer overall survival (OS). An early decline in cCSCs remained an independent prognostic indicator for OS and PFS in multivariate analysis.

CONCLUSIONS: A cCSC decline after one cycle of chemotherapy for metastatic breast cancer is predictive of a superior chemotherapy response and longer PFS and OS, implying that cCSC dynamic monitoring may be helpful in early prediction of treatment response and prognosis.}, } @article {pmid35855704, year = {2022}, author = {Bhatia, JK and Chaudhary, T and Boruah, D and Bharadwaj, R}, title = {Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.}, journal = {Medical journal, Armed Forces India}, volume = {78}, number = {3}, pages = {345-354}, pmid = {35855704}, issn = {0377-1237}, abstract = {BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.

METHODS: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated.

RESULTS: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels.

CONCLUSIONS: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.}, } @article {pmid35855193, year = {2022}, author = {Somashekhar, SP and Jaiswal, R and Kumar, R and Ashok, BC and Rakshit, S and Rauthan, A and Patil, P and Yashas, N and Karthik, HK and Prasad, A and Islam, H and Ashwin, KR}, title = {An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.}, journal = {European journal of breast health}, volume = {18}, number = {3}, pages = {271-278}, pmid = {35855193}, issn = {2587-0831}, abstract = {OBJECTIVE: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer.

MATERIALS AND METHODS: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category.

RESULTS: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively.

CONCLUSION: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.}, } @article {pmid35852797, year = {2022}, author = {Tokura, M and Nakayama, J and Prieto-Vila, M and Shiino, S and Yoshida, M and Yamamoto, T and Watanabe, N and Takayama, S and Suzuki, Y and Okamoto, K and Ochiya, T and Kohno, T and Yatabe, Y and Suto, A and Yamamoto, Y}, title = {Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {82}, number = {18}, pages = {3236-3248}, doi = {10.1158/0008-5472.CAN-22-0090}, pmid = {35852797}, issn = {1538-7445}, mesh = {Biomarkers ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Female ; Gene Expression Profiling ; Humans ; }, abstract = {UNLABELLED: Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC.

SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.}, } @article {pmid35851387, year = {2022}, author = {Thennavan, A and Garcia-Recio, S and Liu, S and He, X and Perou, CM}, title = {Molecular signatures of in situ to invasive progression for basal-like breast cancers: An integrated mouse model and human DCIS study.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {83}, pmid = {35851387}, issn = {2374-4677}, support = {R01 CA148761/CA/NCI NIH HHS/United States ; RO1-CA148761//Breast Cancer Research Foundation (BCRF)/ ; RO1-CA195740//Breast Cancer Research Foundation (BCRF)/ ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of Invasive Ductal Carcinoma (IDC) and thus the identification of features that may predict DCIS progression would be of potential clinical value. Experimental mouse models can be used to address this challenge by studying DCIS-to-IDC biology. Here we utilize single cell RNA sequencing (scRNAseq) on the C3Tag genetically engineered mouse model that forms DCIS-like precursor lesions and for which many lesions progress into end-stage basal-like molecular subtype IDC. We also perform bulk RNAseq analysis on 10 human synchronous DCIS-IDC pairs comprised of estrogen receptor (ER) positive and ER-negative subsets and utilize 2 additional public human DCIS data sets for comparison to our mouse model. By identifying malignant cells using inferred DNA copy number changes from the murine C3Tag scRNAseq data, we show the existence of cancer cells within the C3Tag pre-DCIS, DCIS, and IDC-like tumor specimens. These cancer cells were further classified into proliferative, hypoxic, and inflammatory subpopulations, which change in frequency in DCIS versus IDC. The C3Tag tumor progression model was also associated with increase in Cancer-Associated Fibroblasts and decrease in activated T cells in IDC. Importantly, we translate the C3Tag murine genomic findings into human DCIS where we find common features only with human basal-like DCIS, suggesting there are intrinsic subtype unique DCIS features. This study identifies several tumor and microenvironmental features associated with DCIS progression and may also provide genomic signatures that can identify progression-prone DCIS within the context of human basal-like breast cancers.}, } @article {pmid35847444, year = {2022}, author = {Minagawa, T and Sugiura, T and Okamura, Y and Ito, T and Yamamoto, Y and Ashida, R and Ohgi, K and Sasaki, K and Uesaka, K}, title = {Clinical implications of lymphadenectomy for invasive ductal carcinoma of the body or tail of the pancreas.}, journal = {Annals of gastroenterological surgery}, volume = {6}, number = {4}, pages = {531-542}, pmid = {35847444}, issn = {2475-0328}, abstract = {AIM: The appropriate extent of lymphadenectomy for pancreatic cancer of the body/tail has not been standardized worldwide. The present study evaluated the optimal extent of harvesting lymph nodes.

METHODS: Patients who underwent distal pancreatectomy for invasive ductal carcinoma of the pancreas between 2007 and 2018 were retrospectively reviewed. Patients were subclassified into three groups depending on the tumor location: pancreatic body (Pb), proximal pancreatic tail (Ptp), and distal pancreatic tail (Ptd). The pancreatic tail was further divided into even sections of Ptp and Ptd. Patterns of lymph node metastasis and the impact of lymph node metastasis on the prognosis were examined.

RESULTS: A total of 120 patients were evaluated. Fifty-eight patients had a tumor in the Pb, 38 in the Ptp, and 24 in the Ptd. No patients with a Ptd tumor had metastasis beyond the peripancreatic and splenic hilar lymph nodes (LN-PSH). All patients with metastasis to the lymph nodes along the common hepatic artery (LN-CHA) or along the left lateral superior mesenteric artery (LN-SMA) also had metastasis to the LN-PSH. Recurrence after surgery occurred significantly earlier in this population. In a multivariate analysis, metastasis to the LN-CHA or LN-SMA (hazard ratio [HR] 3.3; P = .04) was an independent risk factor for overall survival. Furthermore, high levels of preoperative serum CA19-9 (HR 10.9; P = .013) were a predictive factor for metastasis to the LN-CHA or LN-SMA.

CONCLUSIONS: Metastasis to the LN-CHA or LN-SMA was rare but a significant prognostic factor in patients with pancreatic body/tail cancer.}, } @article {pmid35846408, year = {2023}, author = {Chen, XY and Thike, AA and Lim, JX and Bay, BH and Tan, PH}, title = {More microinvasive foci in larger tumours of breast ductal carcinoma in situ.}, journal = {Singapore medical journal}, volume = {64}, number = {8}, pages = {493-496}, pmid = {35846408}, issn = {2737-5935}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating ; Prognosis ; Disease-Free Survival ; Progression-Free Survival ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/pathology ; Neoplasm Invasiveness ; }, abstract = {INTRODUCTION: Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.

METHODS: The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.

RESULTS: Higher numbers of Mi foci were found in larger tumours (P = 0.031).

CONCLUSION: Greater extent of DCIS is associated with multifocal Mi.}, } @article {pmid35846138, year = {2022}, author = {Niu, X and Ren, L and Wang, S and Gao, D and Ma, M and Hu, A and Qi, H and Zhang, S}, title = {High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {952335}, pmid = {35846138}, issn = {1664-8021}, abstract = {Background: Gastric cancer (GC) has a high mortality rate and is particularly prevalent in China. The extracellular matrix protein, prolyl 4-hydroxylase subunit alpha 3 (P4HA3), has been implicated in various cancers. We aimed to assess the diagnostic and prognostic value of P4HA3 in GC and investigate its correlation with immune cell infiltration. Methods: The present study used microarray data from the Cancer Genome Atlas (TCGA) to analyze the association of P4HA3 expression with clinicopathological features. Data from the Gene Expression Omnibus (GEO) were used for validation. Receiver operating characteristic (ROC) and Kaplan-Meier curves were constructed to determine the diagnostic and prognostic value of P4HA3 in GC. Univariate and multivariate regression analyses were performed to assess the impact of P4HA3 on overall survival (OS) rates. A protein-protein interaction (PPI) network was generated and functional enrichment evaluated. Single-sample gene set enrichment analysis (ssGSEA) was conducted to correlate P4HA3 expression with immune cell infiltration. The correlation between P4HA3 and immune check point genes was studied. Results: P4HA3 was over-expressed in GC, along with 15 other types of cancer, including breast invasive carcinoma and cholangiocarcinoma. P4HA3 showed high diagnostic and prognostic value in GC and was an independent prognostic factor. P4HA3, TNM (tumor, node, metastases) stage, pathological stage and age all correlated with OS rates. Genes related to P4HA3 were enriched in the lumen of the endoplasmic reticulum and included procollagen-proline 3-dioxygenase activity. P4HA3 expression correlated with numbers of macrophages, natural killer (NK) cells, immature dendritic cells (iDC), mast cells, eosinophils, effective memory T cells (Tem), T-helper 1 (Th1) cells and dendritic cells (DC). P4HA3 was positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2) and programmed cell death 1 ligand 2 (PDCD1LG2). Conclusion: P4HA3 is a potential independent biomarker for prognosis of GC and may be an immunotherapy target in the treatment of GC.}, } @article {pmid35842661, year = {2022}, author = {Zhang, WT and Zhu, GL and Xu, WQ and Zhang, W and Wang, HZ and Wang, YB and Li, YX}, title = {Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer.}, journal = {Diagnostic pathology}, volume = {17}, number = {1}, pages = {61}, pmid = {35842661}, issn = {1746-1596}, support = {No.2008085QH408//Natural Science Foundation of Anhui Province/ ; No.81874063//National Natural Science Foundation of China/ ; }, mesh = {B7-H1 Antigen/metabolism ; Biomarkers, Tumor/analysis ; *Breast Neoplasms ; *Epstein-Barr Virus Infections/complications ; Female ; Herpesvirus 4, Human ; Humans ; Ligands ; Prognosis ; Programmed Cell Death 1 Receptor ; }, abstract = {PURPOSE: Causative factors of breast cancer include infections, such as Epstein-Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.

METHODS: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.

RESULTS: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan-Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.

CONCLUSIONS: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.}, } @article {pmid35837116, year = {2022}, author = {Yang, L and Li, Z and Liang, X and Xu, J and Cai, Y and Huang, C and Zhang, M and Yao, J and Song, B}, title = {Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {934291}, pmid = {35837116}, issn = {2234-943X}, abstract = {PURPOSE: To assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models.

MATERIALS AND METHODS: We retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (<10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test.

RESULTS: Overall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P.

CONCLUSIONS: Radiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.}, } @article {pmid35836477, year = {2022}, author = {Wu, X and Liu, Y and Zhu, J and Yu, W and Lin, X}, title = {A Prospective Trial of the Microneedle Fractional Radiofrequency System Application in the Treatment of Infraorbital Dark Circles.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {15}, number = {}, pages = {1293-1300}, pmid = {35836477}, issn = {1178-7015}, abstract = {BACKGROUND: Infraorbital dark circles (IDC) are commonly consulted in aesthetic practice. There is not yet a multifactorial approach to facilitating their treatment.

OBJECTIVE: To investigate the safety and efficacy of the microneedle fractional radiofrequency (MRF) system for the treatment of IDC.

METHODS: A prospective, split-face, evaluator-blind clinical trial was conducted to study the change in the overall appearance, color, and wrinkles in 21 female patients with mixed type IDC before and after MFR treatment.

RESULTS: Both patients and independent evaluators found significant improvement on the global aesthetic scales after the MFR treatment, especially on periorbital wrinkles (p=0.031). Trends in decreased melanin density in the IDC area were found, but no statistical differences were established. No side effects were observed.

CONCLUSION: MFR is a safe and effective modality for improving mixed type IDC by correcting the structural factors.}, } @article {pmid35834927, year = {2022}, author = {Syamsu, SA and Setiady, R and Smaradania, N and Prihantono, and Irsandy, F and Faruk, M}, title = {Synchronous breast cancer and non-Hodgkin lymphoma: A case report.}, journal = {International journal of surgery case reports}, volume = {97}, number = {}, pages = {107398}, pmid = {35834927}, issn = {2210-2612}, abstract = {INTRODUCTION: Among women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.

PRESENTATION OF CASE: A 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.

CLINICAL DISCUSSION: Treating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.

CONCLUSION: The enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.}, } @article {pmid35821630, year = {2022}, author = {Ciudad, P and Escandón, JM and Manrique, OJ and Gutierrez-Arana, J and Mayer, HF}, title = {Lymphedema prevention and immediate breast reconstruction with simultaneous gastroepiploic vascularized lymph node transfer and deep inferior epigastric perforator flap: A case report.}, journal = {Microsurgery}, volume = {42}, number = {6}, pages = {617-621}, doi = {10.1002/micr.30939}, pmid = {35821630}, issn = {1098-2752}, mesh = {*Breast Neoplasms/complications/surgery ; Female ; Humans ; Lymph Nodes/blood supply ; *Lymphedema/etiology/prevention & control/surgery ; *Mammaplasty/adverse effects/methods ; Mastectomy/adverse effects ; Middle Aged ; *Perforator Flap/blood supply ; }, abstract = {Breast cancer-related lymphedema following axillary lymph node dissection (ALND) has been documented in 6%-55% of patients, mostly occurring within the next 3 years after radiation or surgery. We present a case of a 53-year-old patient with hormone positive, stage IB, left breast invasive ductal carcinoma treated with immediate lymphatic and microvascular breast reconstruction (MBR) using vascularized lymph node transfer (VLNT) for lymphedema prevention. A deep inferior epigastric perforator (DIEP) flap (18.3 × 11.2-cm) and simultaneous prophylactic gastroepiploic-VLNT (7 × 3-cm), orthotopically inset in the axilla, were used for reconstruction following mastectomy and radical ALND. The procedure was uneventful. The patient did not display increased postoperative arm circumferences. ICG lymphography did not show any changes at 2- and 3-years after surgery. Preventive lymphatic reconstruction with GE-VLNT and immediate MBR using the DIEP flap offers a new possibility for the primary prevention of lymphedema and simultaneous immediate autologous breast reconstruction without the risk of iatrogenic lymphedema. Further studies will be directed to unveil the external validity of these findings and the risk reduction rate of this approach.}, } @article {pmid35810223, year = {2022}, author = {Abel, MK and Shui, AM and Chien, AJ and Rugo, HS and Melisko, M and Baehner, F and Mukhtar, RA}, title = {The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study.}, journal = {Annals of surgical oncology}, volume = {29}, number = {12}, pages = {7739-7747}, pmid = {35810223}, issn = {1534-4681}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; K08CA256047/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Cohort Studies ; Databases, Factual ; Female ; Humans ; Middle Aged ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1-3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology.

METHODS: We performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I-III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1-3 positive nodes and RS ≤25 who did and did not receive chemotherapy.

RESULTS: Overall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1-3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1-3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC.

CONCLUSION: Our findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.}, } @article {pmid35805604, year = {2022}, author = {Shenkman, G and Levy, S and Winkler, ZB and Bass, D and Geller, S}, title = {Higher Levels of Postnatal Depressive Symptomatology, Post-Traumatic Growth, and Life Satisfaction among Gay Fathers through Surrogacy in Comparison to Heterosexual Fathers: A Study in Israel in Times of COVID-19.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {13}, pages = {}, pmid = {35805604}, issn = {1660-4601}, mesh = {*COVID-19 ; Fathers/psychology ; Female ; Heterosexuality/psychology ; Homosexuality, Male/psychology ; Humans ; Israel/epidemiology ; Male ; Personal Satisfaction ; *Posttraumatic Growth, Psychological ; Pregnancy ; *Sexual and Gender Minorities ; Surrogate Mothers/psychology ; }, abstract = {This study aimed to explore the psychological welfare, as indicated by postnatal depressive symptomatology, life satisfaction, and posttraumatic growth (growth after contending with stressful birth events), of Israeli gay fathers through surrogacy in comparison to heterosexual fathers. For that purpose, a sample of 167 Israeli fathers (M = 35.6, SD = 4.4) was recruited (68 identified as gay fathers through surrogacy and 99 as heterosexual fathers). Participants completed questionnaires assessing their postnatal depressive symptomatology, life satisfaction, and sense of posttraumatic growth after becoming fathers. Results indicated that gay fathers through surrogacy reported higher levels of life satisfaction and posttraumatic growth than heterosexual fathers. Yet, gay fathers also reported higher levels of postnatal depressive symptomatology than heterosexual fathers when life satisfaction or posttraumatic growth values were low or medium. The findings were interpreted in light of the hardships associated with cross-border surrogacy and the psychological outcomes associated with succeeding to become fathers after contending with them. The study contributes to the limited literature on postnatal depressive symptomatology and posttraumatic growth among gay fathers through surrogacy and provides clinicians and policymakers with relevant information on the psychological strengths and potential difficulties associated with cross-border surrogacy among gay fathers.}, } @article {pmid35804316, year = {2022}, author = {Chang, C and Zhu, J and Li, H and Yang, Q}, title = {Enhanced magnetic resonance imaging manifestations of paediatric intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: case report and literature review.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {400}, pmid = {35804316}, issn = {1471-2431}, mesh = {*Calcinosis/diagnostic imaging ; Cervical Vertebrae/diagnostic imaging ; Child ; Female ; Humans ; *Intervertebral Disc/diagnostic imaging/pathology ; Longitudinal Ligaments/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging ; Osteogenesis ; }, abstract = {BACKGROUND: Since the first description of paediatric intervertebral disc calcification (IDC) by Báron in 1924, only approximately 400 cases have been reported in the literature. Paediatric IDC combined with ossification of the posterior longitudinal ligament (OPLL) is an even rarer condition, with only 8 cases described in detail to date. In this paper, we present a review of the disease characteristics described in the relevant English language literature and discuss the possible mechanisms of lesion enhancement in contrast-enhanced magnetic resonance imaging (MRI).

CASE PRESENTATION: In May 2020, a 6-year-old Han nationality girl presented with the chief complaint of neck pain that had lasted for a week. She did not report a history of trauma or a past illness. On admission, there was no personal and family history, congenital diseases, or non-specific infections such as tuberculosis, among others. Further physical examination revealed that the movement of her cervical spine was limited. Computed tomography (CT) and MRI revealed ossification of the intervertebral discs and posterior longitudinal ligament (PLL) at the C4/5 levels and an absence of obvious spinal cord compression. When contrast-enhanced MRI was performed, significant enhancement was observed in the intervertebral discs and PLL at the C4/5 level. We adopted a non-interventional approach and performed an imaging re-examination 8 months later. Both the plain and contrast-enhanced MRI scans indicated swelling in the C4/5 intervertebral discs and disappearance of the previously observed enhancement in the nucleus pulposus (NP) and PLL at the corresponding levels; CT examination revealed that the ossified lesions had been completely resorbed.

CONCLUSION: Obvious lesion enhancement in contrast-enhanced MRI is an extremely rare manifestation of paediatric IDC combined with OPLL. However, the exact mechanisms of this phenomenon remain unclear. We surmise that it may be caused by a series of biophysical changes related to vertebral endplate injury and repair, but further research will be required for in-depth investigation.}, } @article {pmid35803346, year = {2022}, author = {de Barros, HA and Remmers, S and Luiting, HB and van Leenders, GJLH and Roobol, MJ and Bekers, EM and Amin, A and Haynes, AM and Delprado, W and Stricker, PD and van der Poel, HG and van der Kwast, TH and van Leeuwen, PJ}, title = {Predictive Value of Cribriform and Intraductal Carcinoma for the Nomogram-based Selection of Prostate Cancer Patients for Pelvic Lymph Node Dissection.}, journal = {Urology}, volume = {168}, number = {}, pages = {156-164}, doi = {10.1016/j.urology.2022.04.043}, pmid = {35803346}, issn = {1527-9995}, mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Retrospective Studies ; Lymph Nodes/pathology ; Lymph Node Excision ; Nomograms ; *Prostatic Neoplasms/pathology ; Lymphatic Metastasis/pathology ; }, abstract = {OBJECTIVE: To assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa).

METHODS: We retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Both nomograms were augmented with CR/IDC. The original model was compared with the CR/IDC-updated model using the likelihood ratio test. The performance of the prediction tools was assessed using calibration, discrimination, and clinical utility.

RESULTS: Overall, 109 (28%) men were diagnosed with LNM. Calibration plots of the Briganti and MSKCC nomograms demonstrated an underestimation of the LNM risk across clinically relevant thresholds (≤15%). The addition of CR/IDC to the Briganti nomogram increased the fit of the data (χ[2](1) = 4.30, P = .04), but did not improve the area under the curve (AUC) (0.69, 95% CI 0.63-0.75 vs 0.69, 95% CI 0.64-0.75). Incorporation of CR/IDC in the MSKCC nomogram resulted in an increased fit on the data (χ[2](1) = 10.04, P <.01), but did not increase the AUC (0.66, 95% CI 0.60-0.72 vs 0.68, 95% CI 0.62-0.74). The addition of CR/IDC to the Briganti and MSKCC nomograms did not improve the clinical risk prediction.

CONCLUSION: Incorporation of CR/IDC into the 2 clinically most used pre-radical prostatectomy nomograms does not improve LNM prediction in a multinational, contemporary PCa cohort.}, } @article {pmid35801025, year = {2022}, author = {Yang, SY and Li, Y and Nie, JY and Yang, ST and Yang, XJ and Wang, MH and Zhang, J}, title = {Metaplastic breast cancer with chondrosarcomatous differentiation combined with concurrent bilateral breast cancer: A case report.}, journal = {World journal of clinical cases}, volume = {10}, number = {15}, pages = {5064-5071}, pmid = {35801025}, issn = {2307-8960}, abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer comprising malignant epithelial and mesenchymal cells. Compared with other invasive breast cancers, MBC is not only histologically distinctly heterogeneous but also has a rapid and aggressive growth pattern, which leads to a significant risk of recurrence and mortality.

CASE SUMMARY: In this study, we report the case of a patient with a large left breast mass diagnosed with bilateral invasive ductal carcinoma in both breasts after a preoperative core needle aspiration biopsy of the bilateral breast mass. The patient received neoadjuvant chemotherapy and underwent bilateral breast modified radical mastectomy. Postoperative pathology suggested carcinosarcoma with predominantly chondrosarcoma in the left breast and invasive ductal carcinoma (luminal B) in the right breast. As the patient did not achieve complete pathological remission after six cycles of neoadjuvant chemotherapy, we administered six months of intensive capecitabine treatment. Then the patient was switched to continuous treatment with endocrine therapy using letrozole + goserelin, and the patient is currently in stable condition. However, as MBC of the breast is concurrently diagnosed with chondrosarcoma differentiation, our case is sporadic.

CONCLUSION: Given the variety of immunohistochemical types of bilateral breast cancer, achieving effective chemotherapy should be a key research focus.}, } @article {pmid35797677, year = {2022}, author = {Kapatia, G and Kaur, S and Kumar, S and Laroiya, I and Singh, G and Sharma, M and Bal, A and Luthra-Guptasarma, M}, title = {Expression of Proteinase-activated Receptor 2 (PAR2) as a Correlate of Concern in Triple-negative Breast Cancer (TNBC).}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {30}, number = {6}, pages = {446-452}, doi = {10.1097/PAI.0000000000001025}, pmid = {35797677}, issn = {1533-4058}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Mastectomy ; Receptor, ErbB-2/metabolism ; *Receptor, PAR-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; *Triple Negative Breast Neoplasms/diagnosis/pathology ; }, abstract = {PURPOSE: Triple-negative breast cancer (TNBC), a highly aggressive cancer with poor outcome and lacking specific diagnostic, prognostic, or targeted therapeutic strategies, constitutes roughly 20% of all breast cancer cases. TNBC cells lack receptors for estrogen, progesterone, and human epidermal growth factor. The effort continues to find a suitable correlate that could serve as a TNBC biomarker, or as therapeutic target, or both.

MATERIALS AND METHODS: A retrospective study was performed with 88 TNBC and 74 non-TNBC patients who had undergone mastectomy/lumpectomy with axillary clearance for carcinoma breast. Immunohistochemical staining was carried out for levels of proteinase-activated receptor 2 (PAR2), encoded by F2RL1 gene, and staining scores were calculated, based on intensity and percentage positivity.

RESULTS: PAR2 levels were markedly upregulated in TNBC patients, compared with patients with other breast cancer subtypes. Amongst different non-TNBC subtypes, higher expression was noted in luminal B (88.8%) and HER2+ (100%), compared with luminal A (52.5%). PAR2 levels were significantly high in TNBC patients with age more than 40 years than corresponding patients of non-TNBC group (P=0.0017). Furthermore, there was a statistically significant increase in levels of PAR2 expression in lymph node negative (P=0.0096) and early stage (P=0.005) of TNBC versus non-TNBC patients. PAR2 staining of ductal carcinoma in situ and invasive ductal carcinoma revealed lower expression in invasive component.

CONCLUSIONS: Our data suggest that PAR2 levels constitute a correlate of concern for TNBC, tying in with a recent report that higher levels of F2RL1 gene expression correlate with poorer disease-free, as well as overall survival in TNBCs.}, } @article {pmid35794948, year = {2022}, author = {Tholany, J and Kobayashi, T and Marra, AR and Schweizer, ML and Samuelson, RJ and Suzuki, H}, title = {Impact of Infectious Diseases Consultation on the Outcome of Patients With Enterococcal Bacteremia: A Systematic Literature Review and Meta-analysis.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac200}, pmid = {35794948}, issn = {2328-8957}, abstract = {BACKGROUND: Enterococcal bacteremia carries significant mortality. While multiple studies have evaluated the impact of infectious disease consultation (IDC) on this condition, these studies were limited by the low numbers of patients enrolled. This systemic literature review and meta-analysis was conducted to determine whether IDC is associated with a mortality benefit among patients with enterococcal bacteremia.

METHODS: We performed a systematic literature search using 5 databases for studies evaluating IDC among patients with enterococcal bacteremia. We conducted a meta-analysis to assess whether IDC was associated with reduced mortality. Random-effects models were used to calculate pooled odds ratios (pORs). Heterogeneity was evaluated using I [2] estimation and the Cochran's Q statistic test.

RESULTS: The systematic literature review revealed 6496 reports, from which 18 studies were evaluated in the literature review and 16 studies in the meta-analysis. When all studies were pooled, the association between IDC and mortality was not statistically significant with a pOR of 0.81 (95% CI, 0.61-1.08) and substantial heterogeneity (I [2] = 58%). When the studies were limited to those reporting multivariate analysis including IDC, there was a significant protective effect of IDC (pOR, 0.40; 95% CI, 0.24-0.68) without heterogeneity (I [2] = 0%). Some studies also showed additional benefits to IDC, including appropriate antibiotic therapy and improved diagnostic use.

CONCLUSIONS: IDC was associated with 60% lower odds of mortality when patients were well-matched, potentially through improvement in the care of patients with enterococcal bacteremia. IDC should be considered part of routine care for patients with enterococcal bacteremia.}, } @article {pmid35789311, year = {2022}, author = {Martinez, EO and Jorns, JM and Kong, AL and Kijak, J and Lee, WY and Huang, CC and Cortina, CS}, title = {Primary Breast Neuroendocrine Tumors: An Analysis of the National Cancer Database.}, journal = {Annals of surgical oncology}, volume = {29}, number = {10}, pages = {6339-6346}, pmid = {35789311}, issn = {1534-4681}, support = {UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1TR001436/TR/NCATS NIH HHS/United States ; UL1TR001436/TR/NCATS NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Hormones ; Humans ; Male ; *Neuroendocrine Tumors/epidemiology/therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Primary breast neuroendocrine tumors (BNETs) represent < 1% of breast cancers. Diagnosing BNETs can be challenging, and a limited amount of cohort data currently exists in literature. We aimed to describe primary BNET characteristics, treatment modalities, and survival outcomes through the National Cancer Database (NCDB).

METHODS: A retrospective cohort analysis was performed using the NCDB from 2004 to 2017. BNET cases were compared with patients with invasive ductal carcinoma (IDC). A matched IDC cohort was created by matching patient age, race, and disease stage. Kaplan-Meier analysis was performed, and hazard ratios (HR) were calculated through the bootstrap sampling method.

RESULTS: A total of 1389 BNET and 1,967,401 IDC cases were identified. When compared with IDC patients, BNET patients were older, had more comorbidities, and were more often male (p < 0.01). BNETs were larger, higher grade, and more frequently hormone receptor negative (p < 0.01). While BNET patients were treated with surgery and radiotherapy (p < 0.01) less often compared with IDC patients, they presented at later disease stage (p < 0.001) and received systemic treatment more frequently (53.5% vs. 40%, p < 0.01). Patients with BNET had increased mortality compared with the matched IDC cohort: stage 1 HR 1.8, stage 2 HR 2.0, stage 3 HR 1.8, and stage 4 HR 1.5 (p < 0.001 for all).

CONCLUSION: Patients with BNET tend to present at higher clinical stages, are more frequently hormone receptor negative, and have inferior overall survival compared with patients with IDC. Further treatment strategies and studies are needed to elucidate optimal therapies to maximize patient outcomes.}, } @article {pmid35785686, year = {2022}, author = {Al Laham, O and Atia, F and Ibrahim, D and Shaheen, J and Hokouk, B}, title = {An exceedingly rare simultaneous incidental occurrence of synchronous primary malignancies; Invasive Ductal Carcinoma and Renal Cell Carcinoma in a male - A Case Report.}, journal = {International journal of surgery case reports}, volume = {96}, number = {}, pages = {107367}, pmid = {35785686}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Synchronous malignancies are defined as the emergence of one or more tumors which either occur simultaneously or within 6 months of each other. Populations older than 50 years of age are the most vulnerable. Documented prevalence rates of synchronous neoplasia are 4.5-11.7 %. To the best of our knowledge, ours is the first documented case of synchronous primary incidental occurrence of Invasive Ductal Carcinoma (IDC) and Renal Cell Carcinoma (RCC) in a Middle Eastern male. This type of co-occurrence must be borne in mind because such neoplastic occurrence is potentially fatal. Documentation is essential to raise awareness and to decrease the resultant morbidity and mortality.

CASE PRESENTATION: We present a case of a 61-year-old male who presented to our clinic with a 22-day-history of gradual, painless, and disproportionate hypertrophy of his left breast. CT scan revealed incidental breast and right kidney masses. Therapeutic intervention included a modified radical mastectomy with Sentinel lymph node excision along with right radical nephrectomy.

CLINICAL DISCUSSION: Treatment of our patient was multimodal. Accurate radiological studying together with clinical examination helped us in making a diagnosis. Treatment options for this pathology consist of a combination of surgery and/or adjuvant therapy.

CONCLUSION: Synchronous IDC and RCC are an extremely rare co-occurrence, especially in males, particularly Middle Eastern males, and more specifically, those presenting asymptomatically as incidental findings. It is vital to further document and study such cases to establish innovative surgical techniques, screening modalities for males, and to overcome the consequential morbidity and mortality.}, } @article {pmid35784659, year = {2022}, author = {Saeed, M and Abdulshakour, BM and Bantan, NAA and Falemban, AH and Abdulla, M and Melibary, EM and Mufti, AH and Taher, MM}, title = {Profile of Male Breast Cancer in Makkah Region of Saudi Arabia: A 4-Year Retrospective Analysis of Radiology and Histopathology.}, journal = {International journal of breast cancer}, volume = {2022}, number = {}, pages = {8831011}, pmid = {35784659}, issn = {2090-3170}, abstract = {BACKGROUND: Mammography is a method widely used for the diagnosis of breast disorders in women and may help detect breast cancer in its early stages. Male breast cancer often remains undiagnosed or is poorly controlled until serious complications arise; therefore, the use of screening methods is needed to help with early diagnosis.

METHODS: From a total of 1,667 registered mammography cases screened, 17 male breast disease cases were included in this study. Mammography and ultrasound data were analyzed by Statistical Package of Social Sciences v.22 (SPSS). Diagnosis was made following biopsy in suspicious cases, and histopathological and immunological findings of all such patients were obtained for final diagnosis.

RESULTS: The mean age of the patients was 35 years (range, 14-70 years); 17.6% of the cases were aged 37 yrs, and 2 cases were aged 51 and 52 yrs. Of the 17 cases, 11 had breast lesions, and skin thickening was observed in only 1 case. The different patterns of lesions detected were asymmetry of the parenchyma, mastitis, and hamartoma (n = 1 each), malignant lesions (n = 2), and gynecomastia (n = 6). According to the BI-RADS categorization, 8 cases were benign, one case was probably benign, and 2 cases were likely malignant. In the 2 cases with malignant lesions, pathological diagnosis was made after hematoxylin and eosin and immunocytochemistry examination as invasive ductal carcinoma (IDC) of no special type (NST), grade II and grade III.

CONCLUSIONS: Most breast lesions in this study population were benign, while IDC was the most common malignancy encountered. Mammography is currently the most accurate and cost-effective method for detecting breast lesions. The findings of our study may help increase awareness of male breast cancer and encourage Saudi men at risk to perform self-breast exam and undergo routine breast screening.}, } @article {pmid35779088, year = {2023}, author = {Sadeghipour, N and Tseng, J and Anderson, K and Ayalasomayajula, S and Kozlov, A and Ikeda, D and DeMartini, W and Hori, SS}, title = {Tumor volume doubling time estimated from digital breast tomosynthesis mammograms distinguishes invasive breast cancers from benign lesions.}, journal = {European radiology}, volume = {33}, number = {1}, pages = {429-439}, pmid = {35779088}, issn = {1432-1084}, support = {W81XWH-18-1-0342//U.S. Department of Defense/ ; R25 CA217729/CA/NCI NIH HHS/United States ; T15 LM007033/LM/NLM NIH HHS/United States ; R25 CA217729//National Cancer Institute/ ; R25 CA217729//National Cancer Institute/ ; T15 LM007033//U.S. National Library of Medicine/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Retrospective Studies ; Tumor Burden ; Mammography/methods ; Breast Density ; Early Detection of Cancer/methods ; }, abstract = {OBJECTIVES: The aim of this study was to determine whether lesion size metrics on consecutive screening mammograms could predict malignant invasive carcinoma versus benign lesion outcome.

METHODS: We retrospectively reviewed suspicious screen-detected lesions confirmed by biopsy to be invasive breast cancers or benign that were visible on current and in-retrospect prior screening mammograms performed with digital breast tomosynthesis from 2017 to 2020. Four experienced radiologists recorded mammogram dates, breast density, lesion type, lesion diameter, and morphology on current and prior exams. We used logistic regression models to evaluate the association of invasive breast cancer outcome with lesion size metrics such as maximum dimension, average dimension, volume, and tumor volume doubling time (TVDT).

RESULTS: Twenty-eight patients with invasive ductal carcinoma or invasive lobular carcinoma and 40 patients with benign lesions were identified. The mean TVDT was significantly shorter for invasive breast cancers compared to benign lesions (0.84 vs. 2.5 years; p = 0.0025). Patients with a TVDT of less than 1 year were shown to have an odds ratio of invasive cancer of 6.33 (95% confidence interval, 2.18-18.43). Logistic regression adjusted for age, lesion maximum dimension, and lesion volume demonstrated that shorter TVDT was the size variable significantly associated with invasive cancer outcome.

CONCLUSION: Invasive breast cancers detected on current and in-retrospect prior screening mammograms are associated with shorter TVDT compared to benign lesions. If confirmed to be sufficiently predictive of benignity in larger studies, lesions visible on mammograms which in comparison to prior exams have longer TVDTs could potentially avoid additional imaging and/or biopsy.

KEY POINTS: • We propose tumor volume doubling time as a measure to distinguish benign from invasive breast cancer lesions. • Logistic regression results summarized the utility of the odds ratio in retrospective clinical mammography data.}, } @article {pmid35776828, year = {2022}, author = {Liu, M and Hu, L and Tang, Y and Wang, C and He, Y and Zeng, C and Lin, K and He, Z and Huo, W}, title = {A Deep Learning Method for Breast Cancer Classification in the Pathology Images.}, journal = {IEEE journal of biomedical and health informatics}, volume = {26}, number = {10}, pages = {5025-5032}, doi = {10.1109/JBHI.2022.3187765}, pmid = {35776828}, issn = {2168-2208}, mesh = {Breast/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; *Deep Learning ; Diagnosis, Computer-Assisted/methods ; Female ; Humans ; Neural Networks, Computer ; }, abstract = {Breast cancer is the most common female cancer in the world, and it poses a huge threat to women's health. There is currently promising research concerning its early diagnosis using deep learning methodologies. However, some commonly used Convolutional Neural Network (CNN) and their variations, such as AlexNet, VGGNet, GoogleNet and so on, are prone to overfitting in breast cancer classification, due to both small-scale breast pathology image datasets and overconfident softmax-cross-entropy loss. To alleviate the overfitting issue for better classification accuracy, we propose a novel framework for breast pathology classification, called the AlexNet-BC model. The model is pre-trained using the ImageNet dataset and fine-tuned using an augmented dataset. We also devise an improved cross-entropy loss function to penalize overconfident low-entropy output distributions and make the predictions suitable for uniform distributions. The proposed approach is then validated through a series of comparative experiments on BreaKHis, IDC and UCSB datasets. The experimental results show that the proposed method outperforms the state-of-the-art methods at different magnifications. Its strong robustness and generalization capabilities make it suitable for histopathology clinical computer-aided diagnosis systems.}, } @article {pmid35776197, year = {2022}, author = {Rakshit, S and Sunny, JS and George, M and Hanna, LE and Leela, KV and Sarkar, K}, title = {T helper cell-mediated epitranscriptomic regulation via m6A RNA methylation bridges link between coronary artery disease and invasive ductal carcinoma.}, journal = {Journal of cancer research and clinical oncology}, volume = {148}, number = {12}, pages = {3421-3436}, pmid = {35776197}, issn = {1432-1335}, support = {ECR/2016/000965//Science and Engineering Research Board/ ; }, mesh = {Humans ; Female ; Methylation ; *Coronary Artery Disease/genetics ; Tumor Suppressor Protein p53 ; RNA/genetics ; T-Lymphocytes, Helper-Inducer ; Lactate Dehydrogenases ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) and coronary artery disease (CAD), remains the greatest cause of death annually in women, driven by complex signalling pathways and shared several predisposing risk factors together. Therefore, it is important to find out the common epigenetic modifications which are responsible for possible disease progression from CAD to IDC.

METHODS: CD4+T cell isolation by MACS, RT2 profiler PCR array, Gene ontology study, m6A RNA methylation, ChIP-qPCR, Q-PCR, CRISPR/Cas9-mediated knockout/overexpression, Lactate dehydrogenase release assay, RDIP-qPCR.

RESULTS: We have identified several epigenetic regulators (e.g., VEGFA, AIMP1, etc.) which are mainly involved in inflammatory pathways in both the diseased conditions. Epitranscriptomic alterations such as m6A RNA methylation found abnormal in CD4+T helper cells in both IDC as well as CAD. CRISPR-Cas9 mediated knockout/overexpression of specific gene (BRCA1) are promising therapeutic approaches in diseased conditions by regulating m6A RNA methylation and also tumor suppressor gene P53. It also affected the R-loop formation which is vulnerable to DNA damage and BRCA1 can also induce CTL mediated cytotoxicity in breast cancer cells.

CONCLUSIONS: Therefore, by understanding the modifications of epigenetic mechanisms, their alterations and interactions will aid in the development of newer therapeutic approaches to stop the possible spread from one disease to another.}, } @article {pmid35775660, year = {2022}, author = {Morin, B and Ahmadi, M and Rector, L and Allen, G}, title = {Development of an integrated duty cycle test method to assess cordwood stove performance.}, journal = {Journal of the Air & Waste Management Association (1995)}, volume = {72}, number = {7}, pages = {629-646}, doi = {10.1080/10962247.2022.2057615}, pmid = {35775660}, issn = {2162-2906}, mesh = {*Air Pollutants/analysis ; Heating/methods ; *Household Articles ; Household Products ; Particulate Matter/analysis ; }, abstract = {The US Environmental Protection Agency's (EPA's) New Source Performance Standards (NSPS) for Residential Wood Heaters (RWH) require certification emission testing of prototype appliances. In 2015, EPA revised those standards to further reduce particulate matter emissions from this critical source. However, to achieve that goal, lower emissions measured in certification tests must reflect lower emissions when the appliance is operated in homes. Woodstove certification tests have used either the Federal Reference Method (FRM), a crib wood method, or a cordwood testing method developed by ASTM International that was designated as a broadly applicable Alternative Test Method (ATM) by the EPA until December 2021, when that status was revoked. There is broad agreement that the FRM and ASTM procedures do not simulate typical fueling and operating of wood stoves in the field, raising questions about the efficacy of the current program. Effective emission reduction efforts require robust, accurate, and reproducible test methods. With input from a range of stakeholders, the Northeast States for Coordinated Air Use Management (NESCAUM) developed the Integrated Duty Cycle Test Method for Certification of Wood-Fired Stoves Using Cordwood (IDC), a cordwood testing protocol designed to improve the efficacy of residential wood heater certification testing. That method was approved by EPA as a broadly applicable ATM in 2021. IDC test runs assess appliance performance under a range of operating and fueling conditions representative of typical consumer use patterns. Unlike previous test methods, the IDC protocol requires three replicate runs to assess appliance performance variability. Including variable fueling and operating conditions, along with the requirement for replicates runs, will increase the effectiveness of certification testing and promote the development of improved wood stove technology. This paper reports on experiments conducted to develop and test the IDC method.Implications: Residential wood heating is one of the largest sources of primary particulate matter pollution nationwide. EPA's New Source Performance Standards (NSPS) establish emission limits for this source category and require certification testing of prototype wood appliances to demonstrate compliance with those limits. However, the operating and fueling requirements in NSPS compliance testing protocols do not represent typical conditions in the field. We developed a new testing approach, the Integrated-Duty Cycle (IDC) Test Method, to address the shortcomings of current certification test approaches. The IDC procedure for cordwood stoves, which was approved by EPA as a broadly applicable alternative test method in 2021, assesses appliance operations over various operating and fueling conditions representing typical consumer use patterns in an integrated run and requires three replicate runs to enable the assessment of variability in stove performance. Stoves certified with this method will be equipped to meet the NSPS limits consistently in field operation.}, } @article {pmid35770272, year = {2022}, author = {Tayubi, IA and Madar, IH}, title = {Biomineralization associated alkaline phosphatase as a potential marker of bone metastasis in the patients with invasive breast cancer.}, journal = {Saudi journal of biological sciences}, volume = {29}, number = {8}, pages = {103340}, pmid = {35770272}, issn = {1319-562X}, abstract = {Breast Cancer is the most predominant form of cancer among women worldwide. It has been rigorously studied for biomarker identifications and therapeutic targets. However, various potential genes and their clinical relevance to breast cancer remain unexplored. The heterogeneity of breast cancer is one of the major challenges in early detection. Several studies have reported the significant role of alkaline phosphate (ALP) in the regulation of tumor growth and overall free survival in the pathogenesis of different cancer, including breast cancer which may offer unique therapeutic targets. Therefore, these findings demand a comprehensive study for the biogenesis of ALP genes. This study aims to expression profiling of alkaline phosphate genes in breast cancer and to identify the key pathways and molecular mechanisms underlying breast cancer proliferation and progression. In this study, the transcriptome profiling of invasive breast carcinoma samples was performed and analyzed. We identified that all the ALP genes were downregulated in both Invasive Lobular and Invasive Ductal Carcinoma patients. To understand the underlying molecular mechanism and the clinical significance for these genes in breast cancer, the expression values of genes were measured in adjacent normal and tumor tissues of patients followed by network analysis and functional enrichment analysis. The overall analysis revealed the highly aberrant expression of ALPL gene among all four ALP genes. We identified the functional significance of RUNX2 and WNT3A in deregulating ALPL. Therefore, our findings suggests that downregulation of ALPL could be a potential marker gene for invasive breast carcinoma progression towards bone metastasis.}, } @article {pmid35765108, year = {2022}, author = {Ogbu, TJ and Scales, SE and de Almeida, MM and van Loenhout, JAF and Speybroeck, N and Guha-Sapir, D}, title = {Predictors of exceeding emergency under-five mortality thresholds using small-scale survey data from humanitarian settings (1999 - 2020): considerations for measles vaccination, malnutrition, and displacement status.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {80}, number = {1}, pages = {160}, pmid = {35765108}, issn = {0778-7367}, abstract = {BACKGROUND: Quantifying the effect of measles containing vaccine (MCV) coverage and the prevalence of global acute malnutrition (GAM) on mortality levels in populations of displaced and crisis-affected resident children is important for intervention programming in humanitarian emergencies.

METHODS: A total of 1597 surveys containing data on under-five death rate, population status (internally displaced, refugee, or crisis-affected resident), measles containing vaccine coverage, and global acute malnutrition were extracted from the Complex Emergency Database (CE-DAT). Under-five mortality rates were dichotomized to those exceeding critical levels or otherwise. A Bayesian multivariable mixed-effect logistic regression model was used to assess the association between an under-five death rate (U5DR) exceeding this threshold and population status (i.e., internally displaced, refugees or residents), GAM prevalence (proxy for food security), and MCV coverage.

RESULTS: The prevalence of GAM, MCV and U5DR were higher in internally displaced children (IDC) with values of 14.6%, 69.9% and 2.07 deaths per 10 000 per day, respectively. Refugee populations had lower average under-five mortality rate (0.89 deaths per 10 000 per day), GAM of 12.0% and the highest measles containing vaccine coverage (80.0%). In crisis-affected residents the prevalence of GAM, MCV and average U5DR are 11.1%, 65.5% and 1.20 deaths per 10 000 per day respectively. In mixed-effect logistic model taking 2 deaths per 10 000 children less than five years old per as emergency threshold (Model III); MCV (AOR = 0.66, 95% Highest Density Interval (HDI): 0.57, 0.78), GAM (AOR = 1.79, 95% HDI: 1.52, 2.12) were associated with a reduction of the odds of U5DR exceeding critical level accounting for country-specific levels of variability. The odds of U5DR exceeding critical level (2/10000/day) in crisis-affected resident children and refugees were 0.36 (95% HDI: 0.22, 0.58) and 0.25(95% HDI: 0.11, 0.55) less than amongst IDP children adjusting for GAM and MCV. In considering country specific yearly median U5DR (model IV) the odds of U5DR exceeding twice the median U5DR were associated with MCV (AOR = 0.72, 95% HDI: 0.64, 0.82), GAM (AOR = 1.53, 95%HDI: 1.34, 1.76). The odds of U5DR exceeding critical level in crisis-affected resident children was 0.30(95% HDI: 0.20, 0.45) less than IDP children, after adjusting for MCV and GAM. We found no difference between the odds of U5DR exceeding twice the country level median U5DR in the refugee population compared to the IDPs.

CONCLUSIONS: In this study vaccination coverage and global acute malnutrition (proxy for food security) were associated with U5DR exceeding critical level. The emergency threshold for IDPs and affected residents is significantly different and consistent across the different outcomes, whereas the result is inconsistent for IDPs and refugees. Continued improvement in measles vaccination coverage and reduction of malnutrition in humanitarian emergencies have the potential to minimize the deterioration of mortality level amongst children in emergency settings. To generate a robust understanding of the critical level of child mortality in displaced and affected resident populations, studies accounting for the impact of the duration of displacement, contextual factors in humanitarian settings, and the level of humanitarian assistance provided are needed.}, } @article {pmid35761974, year = {2022}, author = {Chen, S and Yang, L and Li, Y}, title = {Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.}, journal = {Emergency medicine international}, volume = {2022}, number = {}, pages = {3158956}, pmid = {35761974}, issn = {2090-2840}, abstract = {OBJECTIVE: To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy.

MATERIALS AND METHODS: The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis.

RESULTS: Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months, the median survival time in the inner upper quadrant group by 67 months, and the median survival time in the inner lower quadrant group by 61 months. The log-rank test showed all P < 0.001.

CONCLUSION: Patients with primary tumors located in the central area have larger tumor diameters. Patients located in the central area, upper inner quadrant, and lower inner quadrant are more likely to have lymphatic metastasis, have a more serious condition, and have a shorter prognosis survival time. Unluminal type, multiple lymph node metastases, vascular invasion, and the location of the primary tumor in the inner quadrant are all independent risk factors for prognosis in patients after modified radical surgery for IDC.}, } @article {pmid35758969, year = {2022}, author = {Abou Shousha, SA and Hussein, B and Shahine, Y and Fadali, G and Zohir, M and Hamed, Y and Hemedah, M and Baheeg, SA and Ibrahim, A and El Shannawy, M and Osman, EM}, title = {Angiogenic activities of interleukin-8, vascular endothelial growth factor and matrix metalloproteinase-9 in breast cancer.}, journal = {The Egyptian journal of immunology}, volume = {29}, number = {3}, pages = {54-63}, pmid = {35758969}, issn = {1110-4902}, mesh = {*Breast Neoplasms ; Female ; Humans ; Interleukin-8/*metabolism ; Mastectomy ; Matrix Metalloproteinase 9/*metabolism ; Neovascularization, Pathologic/metabolism/pathology ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/*metabolism ; Vascular Endothelial Growth Factors ; }, abstract = {Angiogenesis is a major contributor to tumor growth and metastasis within breast cancer tumor microenvironment in which different proangiogenic factors have been identified and associated with tumor progression, metastasis and poor prognosis. The aim of the current study was to evaluate the angiogenesis among breast cancer patients through ex vivo assessment of the angiogenic factors interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF)-A expressions in excised tumor tissues as well as matrix metalloproteinase 9 (MMP-9) serum levels as well as the prognostic value of MMP-9. Our study included 28 invasive ductal carcinoma female patients who were scheduled for modified radical mastectomy at Medical Research Institute, Alexandria University, Egypt and 10 control subjects. Both IL-8 and VEGF-A expressions were immunohistochemically detected in tumor tissues and serum MMP-9 was determined by ELISA. Although no significant correlations were found between each of IL-8, VEGF-A, MMP-9 levels, and patients' clinicopathological parameters, a significant positive correlation was found between these angiogenic factors each other suggesting their synergistic roles in proceeding angiogenesis. Higher serum MMP-9 level was detected in breast cancer patients compared to the control group, indicating that it can be used as a prognostic biomarker in breast cancer patients.}, } @article {pmid35758185, year = {2022}, author = {Kench, JG and Amin, MB and Berney, DM and Compérat, EM and Cree, IA and Gill, AJ and Hartmann, A and Menon, S and Moch, H and Netto, GJ and Raspollini, MR and Rubin, MA and Tan, PH and Tsuzuki, T and Turjalic, S and van der Kwast, TH and Zhou, M and Srigley, JR}, title = {WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer.}, journal = {Histopathology}, volume = {81}, number = {4}, pages = {447-458}, pmid = {35758185}, issn = {1365-2559}, mesh = {Androgen Antagonists ; *Carcinoma, Ductal/pathology ; Humans ; Male ; *Prostatic Intraepithelial Neoplasia/pathology ; *Prostatic Neoplasms/pathology ; World Health Organization ; }, abstract = {The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)-like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to "adenoid cystic (basal cell) cell carcinoma" given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.}, } @article {pmid35754328, year = {2022}, author = {Ghafil, JA and İbrahim, BMS and Zgair, AK}, title = {Coating indwelling urinary catheters with moxifloxacin prevents biofilm formation by Burkholderia cepacia.}, journal = {Polimery w medycynie}, volume = {52}, number = {1}, pages = {7-11}, doi = {10.17219/pim/149986}, pmid = {35754328}, issn = {0370-0747}, mesh = {Biofilms ; *Burkholderia cepacia ; Catheters, Indwelling ; Moxifloxacin/pharmacology ; Urinary Catheterization ; Urinary Catheters ; }, abstract = {BACKGROUND: Burkholderia cepacia adhesion and biofilm formation onto abiotic surfaces is an important feature of clinically relevant isolates. The in vitro biofilm formation of B. cepacia onto coated indwelling urinary catheters (IDCs) with moxifloxacin has not been previously investigated.

OBJECTIVES: To examine the ability of B. cepacia to form biofilms on IDCs and the effect of coating IDCs with moxifloxacin on biofilm formation by B. cepacia in vitro.

MATERIAL AND METHODS: The adhesion of B. cepacia to coated and uncoated IDCs with moxifloxacin was evaluated. Pieces of IDCs were coated with moxifloxacin (adsorption method). The spectrophotometric method was used to check moxifloxacin leaching into tubes. Coated and uncoated tubes were incubated with 107 colony forming units (cfu)/mL of B. cepacia. The viable bacterial count was used to count the number of bacteria adhered to coated and uncoated IDC pieces.

RESULTS: A significant adhesion of B. cepacia to uncoated IDC pieces started 15 min after the incubation in a bacterial suspension (107 cfu/mL). A maximum adhesion was observed at 48 h. The pretreatment of IDCs with 100 μg/mL of moxifloxacin produced the best adsorption of antibiotic onto the IDCs. Coating IDC pieces with moxifloxacin significantly reduced the adhesion and biofilm formation of B. cepacia (p < 0.05) at various time intervals (1 h, 4 h and 24 h).

CONCLUSIONS: The present study has demonstrated for the first time that coated IDCs with moxifloxacin reduce B. cepacia adhesion and biofilm formation. This finding has opened the door to the production of the new generation IDCs that prevent bacteria from attaching and forming biofilms.}, } @article {pmid35752823, year = {2022}, author = {Jeong, Y and Jin, M and Kim, KS and Na, K}, title = {Biocompatible carbonized iodine-doped dots for contrast-enhanced CT imaging.}, journal = {Biomaterials research}, volume = {26}, number = {1}, pages = {27}, pmid = {35752823}, issn = {1226-4601}, support = {NRF-2022R1A2B5B03001432//Ministry of Science and ICT, South Korea/ ; }, abstract = {BACKGROUND: Computed tomography (CT) imaging has been widely used for the diagnosis and surveillance of diseases. Although CT is attracting attention due to its reasonable price, short scan time, and excellent diagnostic ability, there are severe drawbacks of conventional CT contrast agents, such as low sensitivity, serious toxicity, and complicated synthesis process. Herein, we describe iodine-doped carbon dots (IDC) for enhancing the abilities of CT contrast agents.

METHOD: IDC was synthesized by one-pot hydrothermal synthesis for 4 h at 180 ℃ and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, NMR, TEM, and DLS. Furthermore, the CT values of IDC were calculated and compared with those of conventional CT contrast agents (Iohexol), and the in vitro and in vivo toxicities of IDC were determined to prove their safety.

RESULTS: IDC showed improved CT contrast enhancement compared to iohexol. The biocompatibility of the IDC was verified via cytotoxicity tests, hemolysis assays, chemical analysis, and histological analysis. The osmotic pressure of IDC was lower than that of iohexol, resulting in no dilution-induced contrast decrease in plasma.

CONCLUSION: Based on these results, the remarkable CT contrast enhancement and biocompatibility of IDC can be used as an effective CT contrast agent for the diagnosis of various diseases compared with conventional CT contrast agents.}, } @article {pmid35752268, year = {2022}, author = {Maimon, A and Yizhar, O and Buchs, G and Heimler, B and Amedi, A}, title = {A case study in phenomenology of visual experience with retinal prosthesis versus visual-to-auditory sensory substitution.}, journal = {Neuropsychologia}, volume = {173}, number = {}, pages = {108305}, pmid = {35752268}, issn = {1873-3514}, mesh = {Adult ; Blindness/surgery ; Humans ; Male ; Phosphenes ; Vision Disorders ; *Visual Prosthesis ; }, abstract = {The phenomenology of the blind has provided an age-old, unparalleled means of exploring the enigmatic link between the brain and mind. This paper delves into the unique phenomenological experience of a man who became blind in adulthood. He subsequently underwent both an Argus II retinal prosthesis implant and training, and extensive training on the EyeMusic visual to auditory sensory substitution device (SSD), thereby becoming the first reported case to date of dual proficiency with both devices. He offers a firsthand account into what he considers the great potential of combining sensory substitution devices with visual prostheses as part of a complete visual restoration protocol. While the Argus II retinal prosthesis alone provided him with immediate visual percepts by way of electrically stimulated phosphenes elicited by the device, the EyeMusic SSD requires extensive training from the onset. Yet following the extensive training program with the EyeMusic sensory substitution device, our subject reports that the sensory substitution device allowed him to experience a richer, more complex perceptual experience, that felt more "second nature" to him, while the Argus II prosthesis (which also requires training) did not allow him to achieve the same levels of automaticity and transparency. Following long-term use of the EyeMusic SSD, our subject reported that visual percepts representing mainly, but not limited to, colors portrayed by the EyeMusic SSD are elicited in association with auditory stimuli, indicating the acquisition of a high level of automaticity. Finally, the case study indicates an additive benefit to the combination of both devices on the user's subjective phenomenological visual experience.}, } @article {pmid35749404, year = {2022}, author = {Hardeman, AA and Han, YJ and Grushko, TA and Mueller, J and Gomez, MJ and Zheng, Y and Olopade, OI}, title = {Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0268693}, pmid = {35749404}, issn = {1932-6203}, support = {K12 CA139160/CA/NCI NIH HHS/United States ; UL1 RR024999/RR/NCRR NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; DNA Copy Number Variations ; Female ; Humans ; Protein Serine-Threonine Kinases ; RNA, Messenger/genetics ; *Triple Negative Breast Neoplasms/genetics ; }, abstract = {Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.}, } @article {pmid35749114, year = {2022}, author = {Weis, S and Hagel, S and Palm, J and Scherag, A and Kolanos, S and Bahrs, C and Löffler, B and Schmitz, RPH and Rißner, F and Brunkhorst, FM and Pletz, MW and , }, title = {Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {6}, pages = {e2218515}, pmid = {35749114}, issn = {2574-3805}, mesh = {Adolescent ; Aged ; *Bacteremia/therapy ; *Communicable Diseases ; Female ; Hospitals ; Humans ; Male ; Referral and Consultation ; Retrospective Studies ; *Staphylococcal Infections/therapy ; Staphylococcus aureus ; Telephone ; Treatment Outcome ; }, abstract = {IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.

OBJECTIVES: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.

This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).

INTERVENTIONS: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.

MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality.

RESULTS: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).

CONCLUSIONS AND RELEVANCE: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.

TRIAL REGISTRATION: drks.de Identifier: DRKS00010135.}, } @article {pmid35743985, year = {2022}, author = {Ortega, MA and Fraile-Martinez, O and García-Montero, C and Borja-Vergel, S and Torres-Carranza, D and Pekarek, L and Arribas, CB and De León-Luis, JA and Sánchez-Rojo, C and Alvarez-Mon, MA and García-Honduvilla, N and Buján, J and Coca, S and Alvarez-Mon, M and Saez, MA and Guijarro, LG}, title = {Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {6}, pages = {}, pmid = {35743985}, issn = {1648-9144}, support = {MITICAD//Comunidad de Madrid/ ; }, mesh = {*Breast Neoplasms/drug therapy/genetics ; *Carcinoma, Ductal, Breast/diagnosis/drug therapy/genetics ; *Carcinoma, Lobular/pathology ; Cyclin D1/therapeutic use ; Cyclooxygenase 2 ; Female ; Humans ; Insulin Receptor Substrate Proteins/genetics ; }, abstract = {Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.}, } @article {pmid35739035, year = {2022}, author = {Clawson, A and Zahir, SF and Stewart, S and Torr, S and Hempenstall, N and Vernon, C and Subedi, S}, title = {Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in Queensland.}, journal = {Infection, disease & health}, volume = {27}, number = {4}, pages = {219-226}, doi = {10.1016/j.idh.2022.05.004}, pmid = {35739035}, issn = {2468-0869}, mesh = {Adult ; Humans ; Urinary Catheters/adverse effects ; Catheters, Indwelling/adverse effects ; Retrospective Studies ; Urinary Catheterization/adverse effects ; *Catheter-Related Infections/epidemiology/etiology ; Inpatients ; Queensland/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Hospitals ; }, abstract = {BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI).

AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI.

METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection.

RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p = 0.03). Age, gender, and catheter reinsertion were not associated with UTI development.

CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.}, } @article {pmid35734688, year = {2022}, author = {Hammood, ZD and Najar, KA and Latif, S and Salih, AM and Kakamad, FH and Mohammed, SH and Ali, RK}, title = {Bilateral invasive ductal carcinoma of the breast; a case report with literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {78}, number = {}, pages = {103743}, pmid = {35734688}, issn = {2049-0801}, abstract = {INTRODUCTION: Carcinoma of breast is a heterogeneous disease. Using their light microscopic appearance, the invasive forms are usually divided into three main types: infiltrating lobular carcinomas, infiltrating ductal carcinomas, and other infiltrating carcinomas. This paper aims to discuss and report a case of bilateral invasive ductal carcinoma of the breast.

CASE REPORT: A 48-year-old female presented with bilateral breast masses of 5-month duration. On examination. she had bilateral palpable breast masses, which were hard, mobile, and irregular. On the right side, there was skin tethering and palpable axillary lymph nodes. Ultrasound examination showed a heterogeneous, irregular, ill-defined, mass-like lesion, seen in the upper outer quadrant of the right breast along with a hypoechoic. irregular mass 12*13mm in the upper outer quadrant of the left breast. FNA showed bilateral invasive ductal carcinoma. Right axillary lymph nodes were positive for adenocarcinoma. She received 4 sessions of NACT which was followed by right-side mastectomy with axillary lymph node dissection and left-side mastectomy with sentinel lymph node biopsy.

DISCUSSION: Bilateral breast carcinomas are very rare. They form 2-5% of all breast malignancies. About 2-11% of breast cancer patients develop cancer in the opposite breast in their lifetime with an incidence rate varying from 4 to 8 per 1000 people per year.

CONCLUSION: Bilateral carcinoma of the breast is very rare. Microscopically, the findings usually reveal infiltrative ductal carcinoma. The treatment of choice is bilateral modified radical mastectomy.}, } @article {pmid35720864, year = {2022}, author = {Gordon, O and Peart Akindele, N and Schumacher, C and Hanlon, A and Simner, PJ and Carroll, KC and Sick-Samuels, AC}, title = {Increasing Pediatric Infectious Diseases Consultation Rates for Staphylococcus aureus Bacteremia.}, journal = {Pediatric quality & safety}, volume = {7}, number = {3}, pages = {e560}, pmid = {35720864}, issn = {2472-0054}, support = {T32 AI052071/AI/NIAID NIH HHS/United States ; }, abstract = {INTRODUCTION: Staphylococcus aureus bacteremia (SAB) in children is associated with significant mortality and morbidity, including recurrent bacteremia. Infectious disease consultation (IDC) improves SAB outcomes in adult patients. However, increasing IDC and impact for pediatric patients with SAB is not well described.

METHODS: This quality improvement project aimed to increase IDC for SAB events at a quaternary pediatric medical center. First, we evaluated the local practices regarding pediatric SAB and engaged stakeholders (July 2018-August 2020). We added an advisory comment supporting IDC for SAB to all blood culture results in September 2020. Using statistical process control charts, we monitored the number of SAB events with IDC before a SAB event without IDC. Finally, we evaluated SAB recurrences before and after initiating the advisory comment.

RESULTS: In the baseline period, 30 of 49 (61%) SAB events received an IDC with a mean of 1.4 SAB events with IDC before a SAB event without IDC. Postintervention, 22 of 23 (96%) SAB events received IDC with a mean of 14 events with IDC before 1 event without IDC. The SAB recurrence rate was 8%, with 6 events in 4 children; none of the index cases resulting in recurrence received an IDC (P = 0.0002), and all occurred before any intervention.

CONCLUSIONS: An electronic advisory comment supporting IDC for SAB significantly increased the rate of pediatric IDC with no further SAB recurrence episodes following intervention. This low-resource intervention may be considered in other pediatric centers to optimize SAB management.}, } @article {pmid35720757, year = {2021}, author = {Enochs, C and Filbrun, AG and Iwanicki, C and Moraniec, H and Lehrmann, J and Stiffler, J and Dagher, S and Tapley, C and Phan, H and Raines, R and Nasr, SZ}, title = {Development of an Interdisciplinary Telehealth Care Model in a Pediatric Cystic Fibrosis Center.}, journal = {Telemedicine reports}, volume = {2}, number = {1}, pages = {224-232}, pmid = {35720757}, issn = {2692-4366}, abstract = {Background: People with cystic fibrosis (PCF) have unique physical and emotional needs, which are best met through interdisciplinary care (IDC). In the midst of the pandemic, our center aimed to begin a telehealth care model with an objective to increase successful care visits from baseline of 0-95% by June 26, 2020, including meeting cystic fibrosis (CF) care standards of IDC visits that are coproduced through agenda setting with PCF. Methods: Shifting IDC for pediatric CF patients to telehealth was part of a quality improvement initiative. Our team used asynchronous virtual visits (VVs), with the IDC team members' VVs done on different days than the physician's. Multiple plan-do-study-act cycles were completed to address evolving telehealth needs, including IDC team member flow logistics, communication with PCF, and surveying PCF for the patient perspective. Rates of IDC and agenda setting were measured from March 16, 2020 to June 26, 2020. Results: IDC VVs were at 86% in March 2020 with fluctuations until mid-May when we reached 100% and achieved sustainability. Agenda setting was reached at 100% and maintained. With continued effort, an additional 46.3% of PCF registered for the patient portal, totaling 90.6% with access. Our survey revealed 100% of PCF were able to see IDC team members that they needed to, with 87% "extremely satisfied" and 13% "somewhat satisfied" with their telehealth experience. Conclusions: Successful telehealth in pediatric CF IDC can be achieved through continuous communication, optimal utilization of available technologies, and may help foster unique opportunities to help improve health outcomes.}, } @article {pmid35719670, year = {2022}, author = {Ssentongo, P and Oh, JS and Amponsah-Manu, F and Wong, W and Candela, X and Acharya, Y and Ssentongo, AE and Dodge, DG}, title = {Breast Cancer Survival in Eastern Region of Ghana.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {880789}, pmid = {35719670}, issn = {2296-2565}, mesh = {Ghana/epidemiology ; Humans ; *Receptor, ErbB-2/metabolism ; Retrospective Studies ; Survival Rate ; *Triple Negative Breast Neoplasms/pathology ; }, abstract = {OBJECTIVE: Five-year overall survival rate of breast cancer in low-income countries (LICs) is significantly lower than in high-resource countries. This study explored clinical and pathological factors influencing mortality in the Eastern region of Ghana.

METHODS: We performed a retrospective medical chart review for patients undergoing surgery and chemotherapy for breast cancer at a regional hospital in Ghana from January 2014 to January 2017. Descriptive and survival analysis was done.

RESULTS: One hundred and twenty-nine patients were included in the study. The median age at presentation was 51 years. Sixty percent of patients presented with poorly differential histological grade III. The most common histological type was invasive ductal carcinoma (83%). Based on stage assessment using only tumor size and lymph node status, 60% presented at stage 3. Only 25% were tested for hormone receptor proteins and HER2 status. Of these, 57% had triple-negative breast cancer (TNBC). The 3-year overall survival rate was only 52%.

CONCLUSION: The cumulative 3-year survival was 52%. Despite success in reducing cancer mortality in northern Africa, survival in sub-Saharan Africa remains poor. A significantly higher percentage of GIII and TNBC is found in breast cancers seen in Ghana. When combined with limited capacity for accurate diagnosis, cancer subtype analysis, adequate therapy, and follow-up, late-stage presentation leads to poor outcomes. Future studies should emphasize the identification of barriers to care and opportunities for cost-effective and sustainable improvements in diagnosing and treating breast cancer in LICs.}, } @article {pmid35719192, year = {2022}, author = {Lu, X and Jing, L and Liu, S and Wang, H and Chen, B}, title = {miR-149-3p Is a Potential Prognosis Biomarker and Correlated with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma.}, journal = {International journal of endocrinology}, volume = {2022}, number = {}, pages = {5006123}, pmid = {35719192}, issn = {1687-8337}, abstract = {BACKGROUND: Endocrine disruption is an important factor in the development of endometrial cancer. Expression of miR-149-3p is observed in some cancer types, while its role in uterine corpus endometrial carcinoma (UCEC) is unclear.

METHODS: The clinical and genomic data and prognostic information on UCEC were obtained for patients from the TCGA database. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between clinical characteristics and miR-149-3p expression. Kaplan-Meier survival curve analysis was used to study the influence of miR-149-3p expression and miR-149-3p target genes on the prognosis of UCEC patients. The TargetScan, PicTar, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the involvement of miR-149-3p target genes in function. Immune infiltration analysis was used to analyze the functional involvement of miR-149-3p. QRT-PCR was used to validate the expression of miR-149-3p in UCEC cell lines.

RESULTS: High expression of miR-149-3p in UCEC was significantly associated with age (P < 0.001), histological type (P < 0.001), histological grade (P < 0.001), tumor invasion (P=0.014), and radiation therapy (P=0.011). High miR-149-3p expression predicted poorer overall survival (OS) (HR: 2.56; 95% CI: 1.64-4.00; P < 0.001), progression-free interval (PFI) (HR: 1.85; 95% CI: 1.29-2.65; P=0.001), and disease-specific survival (DSS) (HR: 2.33; 95% CI: 1.37-3.99; P=0.002). Low expressions of miR-149-3p target genes, including ADCYAP1R1, CGNL1, CHST3, CYGB, DNAH9, ESR1, HHIP, HIC1, HOXD11, IGF1, INMT, LSP1, MTMR10, NFIC, PLCE1, RARA, SNTN, SPRYD3, and ZBTB7A, were associated with poor OS in UCEC. MiR-149-3p may be involved in the occurrence and development of UCEC via pathways including PI3K-Akt signaling pathway, Ras signaling pathway, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and MAPK signaling pathway. miR-149-3p may inhibit the function of CD8 T cells, cytotoxic cells, eosinophils, iDC, mast cells, neutrophils, NK CD56bright cells, NK CD56dim cells, pDC, T cells, T helper cells, TFH, Th17 cells, and Treg. miR-149-3p was significantly upregulated in UCEC cell lines compared with endometriotic stromal cells.

CONCLUSION: High expression of miR-149-3p was significantly associated with poor survival in UCEC patients. It may be a promising biomarker of prognosis and response to immunotherapy for UCEC patients.}, } @article {pmid35714570, year = {2022}, author = {Sakurai, M and Weber, P and Wolff, G and Wieder, A and Szendroedi, J and Herzig, S and Ekim Üstünel, B}, title = {TSC22D4 promotes TGFβ1-induced activation of hepatic stellate cells.}, journal = {Biochemical and biophysical research communications}, volume = {618}, number = {}, pages = {46-53}, doi = {10.1016/j.bbrc.2022.05.100}, pmid = {35714570}, issn = {1090-2104}, mesh = {Diabetes Mellitus, Type 2/metabolism/pathology ; *Hepatic Stellate Cells/metabolism/pathology ; Humans ; *Liver Cirrhosis/metabolism/pathology ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology ; *Transcription Factors/metabolism ; *Transforming Growth Factor beta1/metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and liver fibrosis emerge as progressive liver diseases that accompany metabolic syndrome usually characterized by obesity, insulin resistance and type 2 diabetes. Currently no FDA approved treatments exist for the treatment of NASH and liver fibrosis, which requires a better knowledge of the underlying molecular mechanisms. TSC22D4 belongs to the TSC-22 protein family, the members of which are regulated by inflammatory and stress signals. Interestingly, patients with type 2 diabetes, with NAFLD as well as with NASH all have elevated levels of hepatic TSC22D4 expression. Previous studies with targeted deletion of TSC22D4 specifically in hepatocytes showed that TSC22D4 not only acts as a critical controller of diabetic hyperglycemia, but also contributes to NAFLD/NASH progression. To gain better insight into the development of progressive liver diseases, here we studied the function of TSC22D4 in hepatic stellate cells (HSCs), which play a key role in the pathogenesis of liver fibrosis. Our results indicated that TSC22D4 contributes to TGFβ1-mediated activation of HSCs and promotes their proliferation and migration. RNA-Sequencing analysis revealed that TSC22D4 initiates transcriptional events associated with HSC activation. Overall, our findings establish TSC22D4 as a key hub in the development of liver fibrosis, acting across different cellular compartments. Combinatorial TSC22D4 targeting in both hepatocytes and HSC may thus show superior efficacy against progressive liver disease.}, } @article {pmid35714104, year = {2022}, author = {Icht, M and Bergerzon-Bitton, O and Ben-David, BM}, title = {Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.}, journal = {International journal of language & communication disorders}, volume = {57}, number = {5}, pages = {1023-1049}, pmid = {35714104}, issn = {1460-6984}, mesh = {Aged ; *Dysarthria/psychology ; Humans ; Linguistics ; Reproducibility of Results ; Speech Disorders/complications ; *Speech Intelligibility ; Speech Production Measurement/methods ; Young Adult ; }, abstract = {'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.}, } @article {pmid35711899, year = {2022}, author = {Choi, JDW and Hughes, TMD and Marx, G and Boyages, J and Rutovitz, J and Hasovits, C and Parasyn, A and Edirimanne, S and Ngui, NK}, title = {The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.}, journal = {The breast journal}, volume = {2022}, number = {}, pages = {1199245}, pmid = {35711899}, issn = {1524-4741}, mesh = {Australia ; *Breast Neoplasms/drug therapy/genetics/pathology ; Female ; Gene Expression Profiling/methods ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Receptors, Estrogen/genetics ; Retrospective Studies ; }, abstract = {INTRODUCTION: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.

METHODS: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).

CONCLUSION: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.}, } @article {pmid35703412, year = {2022}, author = {Gong, AJ and Nguyen, DL and Lee, EE and Mullen, LA and Myers, KS and Oluyemi, E and Ambinder, EB}, title = {Comparison of Outcomes for One-View Asymmetries Recalled From Digital Breast Tomosynthesis Versus Full-Field Digital Mammography Screening Examinations.}, journal = {AJR. American journal of roentgenology}, volume = {219}, number = {5}, pages = {724-733}, doi = {10.2214/AJR.22.27820}, pmid = {35703412}, issn = {1546-3141}, mesh = {Humans ; Middle Aged ; Aged ; Female ; *Mammography/methods ; Early Detection of Cancer/methods ; *Breast Neoplasms/diagnostic imaging ; Retrospective Studies ; Breast Density ; }, abstract = {BACKGROUND. Recall rates are lower for digital breast tomosynthesis (DBT) than for full-field digital mammography (FFDM). This difference could have important implications with respect to one-view asymmetries given that missed cancers are often visible on one view. OBJECTIVE. The purpose of this study is to compare the outcomes of one-view asymmetries recalled from DBT versus FFDM screening examinations and to determine predictors of malignancy among recalled asymmetries. METHODS. This retrospective study first determined recall rates associated with one-view asymmetries for screening mammography performed using DBT and FFDM from July 14, 2016, through July 14, 2020. Further analyses included patients recalled for a one-view asymmetry who completed subsequent diagnostic workup and all recommended follow-up. Patient and cancer characteristics were extracted from the electronic health record. RESULTS. The recall rate associated with asymmetries was lower for DBT screening (2.5% [3169/128,755]) than for FFDM screening (3.4% [815/23,898]) (p < .001). Further analyses of patients who completed diagnostic workup and subsequent follow-up included 3119 patients (mean age, 57 years) for DBT screening and 811 patients (mean age, 56 years) for FFDM screening. Distribution of final BI-RADS categories from subsequent diagnostic workup was not different between the two modalities (p > .99). The frequency of malignancy was not different between asymmetries recalled from DBT (1.7% [54/3119]) and FFDM (1.7% [14/811]) (p > .99). Malignant asymmetries identified on FFDM versus DBT were more frequently associated with architectural distortion on diagnostic workup (35.7% [5/14] vs 9.3% [5/54]) (p < .001) and were more commonly invasive ductal carcinoma (92.9% vs 57.4%) and less commonly invasive lobular carcinoma (0.0% vs 24.1%) (p = .05). In multivariable analysis, independent predictors of malignancy among recalled asymmetries from DBT were age (for 55-69 years, odds ratio [OR] = 2.40 [p = .04]; for ≥ 70 years, OR = 7.93 [p < .001]; reference, < 55 years) and breast density (not dense, OR = 2.47 [p = .001]; reference, dense breasts). CONCLUSION. Recalled asymmetries were less frequent for DBT than for FFDM. The malignancy rate was low for both modalities (1.7%). Age 55 years old and older and lower breast density predicted malignancy for DBT-recalled asymmetries. CLINICAL IMPACT. Our results support the use of DBT to reduce unnecessary recalls without altering PPV for asymmetry-associated malignancies. Patient factors should be considered when assessing whether a potential asymmetry on DBT screening represents overlapping fibroglandular tissue or a suspicious finding that requires diagnostic workup.}, } @article {pmid35700595, year = {2022}, author = {Chen, YQ and Xu, XF and Xu, JW and Di, TY and Wang, XL and Huo, LQ and Wang, L and Gu, J and Zhou, GH}, title = {A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis.}, journal = {Translational oncology}, volume = {22}, number = {}, pages = {101467}, pmid = {35700595}, issn = {1936-5233}, abstract = {BACKGROUND: Breast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments.

PATIENTS AND METHODS: A total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram.

RESULTS: Nomograms were constructed for the breast NEC and breast IDC groups after PSM. The C-index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818-0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone.

CONCLUSIONS: We established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.}, } @article {pmid35697697, year = {2022}, author = {Rebbeck, CA and Xian, J and Bornelöv, S and Geradts, J and Hobeika, A and Geiger, H and Alvarez, JF and Rozhkova, E and Nicholls, A and Robine, N and Lyerly, HK and Hannon, GJ}, title = {Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3399}, pmid = {35697697}, issn = {2041-1723}, support = {A21143/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Homeodomain Proteins/genetics/metabolism ; Humans ; Transcription Factors/genetics ; Transcriptome ; }, abstract = {Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.}, } @article {pmid35695947, year = {2023}, author = {Gur, N and Zimmerman-Brenner, S and Fattal-Valevski, A and Rotstein, M and Pilowsky Peleg, T}, title = {Group comprehensive behavioral intervention for tics contribution to broader cognitive and emotion regulation in children.}, journal = {European child & adolescent psychiatry}, volume = {32}, number = {10}, pages = {1925-1933}, pmid = {35695947}, issn = {1435-165X}, mesh = {Adolescent ; Child ; Humans ; *Tics/therapy/complications ; *Emotional Regulation ; Severity of Illness Index ; *Tic Disorders/psychology ; *Tourette Syndrome/psychology ; Cognition ; }, abstract = {There is increasing evidence for the effectiveness of behavioral techniques in managing tics in youth with Tourette syndrome and tics disorders (TDs). One such intervention is Comprehensive Behavioral Intervention for Tics (CBIT), which focuses on reducing tic severity by training control and regulation. In view of the regulation deficits characteristic to TDs, in the current study, we aimed to explore the contribution of CBIT beyond tic control, to a wider expression of regulation abilities-cognitive inhibition and emotion regulation. A total of 55 participants with TDs, aged 8-15, who were randomly assigned to group-CBIT or group-Educational Intervention for Tics, were compared on cognitive inhibition tests and use of emotion-regulation strategies, pre- and post-intervention. Whereas on none of the scales a significant interaction effect was found reflecting superiority of CBIT over EIT, repeated measures ANOVA revealed a significant time effect, with post hoc analyses indicating that cognitive inhibition and cognitive reappraisal significantly increased following CBIT intervention only. Within the group-CBIT, the increase in cognitive reappraisal was associated with higher intellectual ability. These findings may lead to a broader understanding of CBIT contribution to more than tic control, but rather to better cognitive and emotional regulation abilities.}, } @article {pmid35695563, year = {2022}, author = {Agostinetto, E and Nader-Marta, G and Paesmans, M and Ameye, L and Veys, I and Buisseret, L and Neven, P and Taylor, D and Fontaine, C and Duhoux, FP and Canon, JL and Denys, H and Coussy, F and Chakiba, C and Ribeiro, JM and Piccart, M and Desmedt, C and Ignatiadis, M and Aftimos, P}, title = {ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.}, journal = {Future oncology (London, England)}, volume = {18}, number = {22}, pages = {2383-2392}, doi = {10.2217/fon-2022-0358}, pmid = {35695563}, issn = {1744-8301}, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; Cadherins ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/pathology ; Clinical Trials, Phase II as Topic ; Female ; Humans ; Neoadjuvant Therapy ; Protein-Tyrosine Kinases/therapeutic use ; Proto-Oncogene Proteins ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.}, } @article {pmid35694092, year = {2022}, author = {Yan, Z and Wong, A and Ng, RP and Lee, YS and Lim, MEA and Leong, LCH and Allen, J and Lim, GH}, title = {Determining the benefit of neoadjuvant chemotherapy in reduction of axillary dissection rates in Z0011 trial cohort with high nodal burden.}, journal = {Gland surgery}, volume = {11}, number = {5}, pages = {788-794}, pmid = {35694092}, issn = {2227-684X}, abstract = {BACKGROUND: In breast cancer patients fulfilling the Z0011 trial criteria, axillary lymph node dissection (ALND) is reserved for patients with a high nodal burden of ≥3 metastatic nodes. In this group of patients, to avoid an ALND, neoadjuvant chemotherapy (NACT) could be given instead to achieve nodal pathological complete response (pCR). However, the benefit of NACT in achieving nodal pCR and avoiding ALND in this group of patients is unknown. We aimed to determine the nodal pCR rate in this group of patients who otherwise would have needed an ALND.

METHODS: cT1-2N0 breast cancer patients, with histologically proven nodal metastasis, who underwent NACT were identified from a prospectively maintained database. The sonographic criteria of ≥3 abnormal nodes, which has been reported as highly predictive of high nodal burden, was then used to identify the high nodal burden group. Nodal pCR was determined based on the ALND following NACT.

RESULTS: Twenty-four patients with high nodal burden were identified. Mean age was 55.2 years. 91.7% had invasive ductal carcinoma and 29.2% had grade III cancer. 54.2% achieved nodal pCR which was associated with ypT (P=0.006). Nodal pCR was 75%, 70% and 30% in the triple negative, human epidermal growth factor receptor2 (HER2) positive and ER/PR+HER2- tumors, respectively.

CONCLUSIONS: In the postulated T1-2 breast cancer patients with high nodal burden, needing an upfront ALND, NACT could result in nodal pCR of 54.2%, with higher pCR in certain subtypes. Hence, to minimize ALND risk, NACT should be offered in this high nodal burden group.}, } @article {pmid35689181, year = {2022}, author = {Lambe, K and Guerra, S and Salazar de Pablo, G and Ayis, S and Cameron, ID and Foster, NE and Godfrey, E and Gregson, CL and Martin, FC and Sackley, C and Walsh, N and Sheehan, KJ}, title = {Effect of inpatient rehabilitation treatment ingredients on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with unplanned admission: an overview review.}, journal = {BMC geriatrics}, volume = {22}, number = {1}, pages = {501}, pmid = {35689181}, issn = {1471-2318}, support = {MR/S032819/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Activities of Daily Living ; Aged ; Humans ; Inpatients ; Length of Stay ; *Patient Discharge ; *Quality of Life ; }, abstract = {BACKGROUND: To synthesise the evidence for the effectiveness of inpatient rehabilitation treatment ingredients (versus any comparison) on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with an unplanned hospital admission.

METHODS: A systematic search of Cochrane Library, MEDLINE, Embase, PsychInfo, PEDro, BASE, and OpenGrey for published and unpublished systematic reviews of inpatient rehabilitation interventions for older adults following an unplanned admission to hospital from database inception to December 2020. Duplicate screening for eligibility, quality assessment, and data extraction including extraction of treatment components and their respective ingredients employing the Treatment Theory framework. Random effects meta-analyses were completed overall and by treatment ingredient. Statistical heterogeneity was assessed with the inconsistency-value (I[2]).

RESULTS: Systematic reviews (n = 12) of moderate to low quality, including 44 non-overlapping relevant RCTs were included. When incorporated in a rehabilitation intervention, there was a large effect of endurance exercise, early intervention and shaping knowledge on walking endurance after the inpatient stay versus comparison. Early intervention, repeated practice activities, goals and planning, increased medical care and/or discharge planning increased the likelihood of discharge home versus comparison. The evidence for activities of daily living (ADL) was conflicting. Rehabilitation interventions were not effective for functional mobility, strength, or quality of life, or reduce length of stay or mortality. Therefore, we did not explore the potential role of treatment ingredients for these outcomes.

CONCLUSION: Benefits observed were often for subgroups of the older adult population e.g., endurance exercise was effective for endurance in older adults with chronic obstructive pulmonary disease, and early intervention was effective for endurance for those with hip fracture. Future research should determine whether the effectiveness of these treatment ingredients observed in subgroups, are generalisable to older adults more broadly. There is a need for more transparent reporting of intervention components and ingredients according to established frameworks to enable future synthesis and/or replication.

TRIAL REGISTRATION: PROSPERO Registration CRD42018114323 .}, } @article {pmid35687769, year = {2022}, author = {Silva, DJ and Miranda, G and Mesquita, A}, title = {Clinical relevance of receptor conversion in metastatic breast cancer: Case report.}, journal = {Medicine}, volume = {101}, number = {23}, pages = {e29136}, pmid = {35687769}, issn = {1536-5964}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/therapy ; Disease Progression ; Female ; Humans ; Mastectomy ; Quality of Life ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.

PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.

DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.

INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated.

OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.

CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.}, } @article {pmid35685958, year = {2022}, author = {da Luz, FAC and da Costa Marinho, E and Nascimento, CP and de Andrade Marques, L and Delfino, PFR and Antonioli, RM and de Araújo, RA and Silva, MJB}, title = {Prognosis value of lymphovascular invasion in patients with invasive ductal breast carcinoma according to lymph node metastasis status.}, journal = {Ecancermedicalscience}, volume = {16}, number = {}, pages = {1364}, pmid = {35685958}, issn = {1754-6605}, abstract = {BACKGROUND: Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma.

METHODS: This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status.

RESULTS: Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406), p = 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010), p = 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728), p = 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335), p = 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509), p = 0.004).

CONCLUSION: The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3).}, } @article {pmid35684680, year = {2022}, author = {Yan, R and Ren, F and Li, J and Rao, X and Lv, Z and Zheng, C and Zhang, F}, title = {Nuclei-Guided Network for Breast Cancer Grading in HE-Stained Pathological Images.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {11}, pages = {}, pmid = {35684680}, issn = {1424-8220}, mesh = {Breast/pathology ; *Breast Neoplasms/pathology ; Cell Nucleus ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Humans ; Image Processing, Computer-Assisted/methods ; }, abstract = {Breast cancer grading methods based on hematoxylin-eosin (HE) stained pathological images can be summarized into two categories. The first category is to directly extract the pathological image features for breast cancer grading. However, unlike the coarse-grained problem of breast cancer classification, breast cancer grading is a fine-grained classification problem, so general methods cannot achieve satisfactory results. The second category is to apply the three evaluation criteria of the Nottingham Grading System (NGS) separately, and then integrate the results of the three criteria to obtain the final grading result. However, NGS is only a semiquantitative evaluation method, and there may be far more image features related to breast cancer grading. In this paper, we proposed a Nuclei-Guided Network (NGNet) for breast invasive ductal carcinoma (IDC) grading in pathological images. The proposed nuclei-guided attention module plays the role of nucleus attention, so as to learn more nuclei-related feature representations for breast IDC grading. In addition, the proposed nuclei-guided fusion module in the fusion process of different branches can further enable the network to focus on learning nuclei-related features. Overall, under the guidance of nuclei-related features, the entire NGNet can learn more fine-grained features for breast IDC grading. The experimental results show that the performance of the proposed method is better than that of state-of-the-art method. In addition, we released a well-labeled dataset with 3644 pathological images for breast IDC grading. This dataset is currently the largest publicly available breast IDC grading dataset and can serve as a benchmark to facilitate a broader study of breast IDC grading.}, } @article {pmid35678506, year = {2022}, author = {Russo, M and Amboni, M and Volzone, A and Ricciardelli, G and Cesarelli, G and Ponsiglione, AM and Barone, P and Romano, M and Ricciardi, C}, title = {Interplay between gait and neuropsychiatric symptoms in Parkinson's Disease.}, journal = {European journal of translational myology}, volume = {32}, number = {2}, pages = {}, pmid = {35678506}, issn = {2037-7452}, abstract = {Parkinson's Disease (PD) is a neurodegenerative disease which involves both motor and non-motor symptoms. Non-motor mental symptoms are very common among patients with PD since the earliest stage. In this context, gait analysis allows to detect quantitative gait variables to distinguish patients affected by non-motor mental symptoms from patients without these symptoms. A cohort of 68 PD subjects (divided in two groups) was acquired through gait analysis (single and double task) and spatial temporal parameters were analysed; first with a statistical analysis and then with a machine learning (ML) approach. Single-task variables showed that 9 out of 16 spatial temporal features were statistically significant for the univariate statistical analysis (p-value< 0.05). Indeed, a statistically significant difference was found in stance phase (p-value=0.032), swing phase (p-value=0.042) and cycle length (p-value=0.03) of the dual task. The ML results confirmed the statistical analysis, in particular, the Decision Tree classifier showed the highest accuracy (80.9%) and also the highest scores in terms of specificity and precision. Our findings indicate that patients with non-motor mental symptoms display a worse gait pattern, mainly dominated by increased slowness and dynamic instability.}, } @article {pmid35677896, year = {2022}, author = {Albogami, S}, title = {Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer.}, journal = {Saudi journal of biological sciences}, volume = {29}, number = {7}, pages = {103318}, pmid = {35677896}, issn = {1319-562X}, abstract = {Breast cancer accounts for nearly half of all cancer-related deaths in women worldwide. However, the molecular mechanisms that lead to tumour development and progression remain poorly understood and there is a need to identify candidate genes associated with primary and metastatic breast cancer progression and prognosis. In this study, candidate genes associated with prognosis of primary and metastatic breast cancer were explored through a novel bioinformatics approach. Primary and metastatic breast cancer tissues and adjacent normal breast tissues were evaluated to identify biomarkers characteristic of primary and metastatic breast cancer. The Cancer Genome Atlas-breast invasive carcinoma (TCGA-BRCA) dataset (ID: HS-01619) was downloaded using the mRNASeq platform. Genevestigator 8.3.2 was used to analyse TCGA-BRCA gene expression profiles between the sample groups and identify the differentially-expressed genes (DEGs) in each group. For each group, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to determine the function of DEGs. Networks of protein-protein interactions were constructed to identify the top hub genes with the highest degree of interaction. Additionally, the top hub genes were validated based on overall survival and immunohistochemistry using The Human Protein Atlas. Of the top 20 hub genes identified, four (KRT14, KIT, RAD51, and TTK) were considered as prognostic risk factors based on overall survival. KRT14 and KIT expression levels were upregulated while those of RAD51 and TTK were downregulated in patients with breast cancer. The four proposed candidate hub genes might aid in further understanding the molecular changes that distinguish primary breast tumours from metastatic tumours as well as help in developing novel therapeutics. Furthermore, they may serve as effective prognostic risk markers based on the strong correlation between their expression and patient overall survival.}, } @article {pmid35676330, year = {2022}, author = {Yu, Y and Lajkosz, K and Finelli, A and Fleshner, N and van der Kwast, TH and Downes, MR}, title = {Impact of cribriform pattern 4 and intraductal prostatic carcinoma on National Comprehensive Cancer Network (NCCN) and Cancer of Prostate Risk Assessment (CAPRA) patient stratification.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {35}, number = {11}, pages = {1695-1701}, pmid = {35676330}, issn = {1530-0285}, mesh = {Male ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Prostate-Specific Antigen ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; Prostatectomy/methods ; Risk Assessment/methods ; *Carcinoma, Intraductal, Noninfiltrating ; }, abstract = {Pretreatment classification tools are used in prostate cancer to inform patient management. The effect of cribriform pattern 4 (CC) and intraductal carcinoma (IDC) on such nomograms is still underexplored. We analyzed the Cancer of Prostate Risk Assessment (CAPRA) and National Comprehensive Cancer Network (NCCN) risk scores in cases with and without CC/IDC to assess impact on biochemical recurrence (BCR) and metastases/death of prostate cancer (event free survival-EFS) after prostatectomy. A matched biopsy- prostatectomy cohort (2010-2017) was reviewed for CC/IDC. CAPRA and NCCN scores were calculated. CAPRA score 0-2 were deemed "low", 3-5 "intermediate" and 6-10 "high". NCCN scores 1-2 "very low/low", 3 "favorable intermediate", 4 "unfavorable intermediate", 5-6 "high/very high". Cases were stratified by presence of CC/IDC. BCR and EFS probabilities were estimated using the Kaplan-Meier method. Prognostic performance was evaluated using log-rank tests and Harrell's concordance index. 612 patients with mean age 63.1 years were included with mean follow up of 5.3 (range 0-10.8) years. CC/IDC was noted in 159/612 (26%) biopsies. There were 101 (17%) BCR and 36 (6%) events. CAPRA discriminated three distinct risk categories for BCR (p < 0.001) while only high risk separated significantly for EFS (p < 0.001). NCCN distinguished two prognostic groups for BCR (p < 0.0001) and three for EFS (p < 0.0001). Addition of CC/IDC to CAPRA impacted scores 3-5 for BCR and scores 3-5 and 6-10 for EFS and improved the overall concordance index (BCR: 0.66 vs. 0.71; EFS: 0.74 vs. 0.80). Addition of CC/IDC to NCCN impacted scores 4 and 5-6 and also improved the concordance index for BCR (0.62 vs. 0.68). Regarding EFS, NCCN scores 4 and 5-6 demonstrated markedly different outcomes with the addition of CC/IDC. The CAPRA nomogram allows better outcome stratification than NCCN. Addition of CC/IDC status particularly improves patient stratification for CAPRA scores 3-5, 6-10, and for NCCN scores 4 and 5-6.}, } @article {pmid35675775, year = {2022}, author = {Fougerat, A and Schoiswohl, G and Polizzi, A and Régnier, M and Wagner, C and Smati, S and Fougeray, T and Lippi, Y and Lasserre, F and Raho, I and Melin, V and Tramunt, B and Métivier, R and Sommer, C and Benhamed, F and Alkhoury, C and Greulich, F and Jouffe, C and Emile, A and Schupp, M and Gourdy, P and Dubot, P and Levade, T and Meynard, D and Ellero-Simatos, S and Gamet-Payrastre, L and Panasyuk, G and Uhlenhaut, H and Amri, EZ and Cruciani-Guglielmacci, C and Postic, C and Wahli, W and Loiseau, N and Montagner, A and Langin, D and Lass, A and Guillou, H}, title = {ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity.}, journal = {Cell reports}, volume = {39}, number = {10}, pages = {110910}, doi = {10.1016/j.celrep.2022.110910}, pmid = {35675775}, issn = {2211-1247}, support = {I 3535/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adipose Tissue/metabolism ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Hepatocytes/metabolism ; Ketone Bodies/metabolism ; *Lipolysis/physiology ; *PPAR alpha/metabolism ; }, abstract = {In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β3-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.}, } @article {pmid35673084, year = {2022}, author = {de Assis, ÉG and do Patrocínio, ZKG and Nobre, CN}, title = {The Use of Convolutional Neural Networks in the Prediction of Invasive Ductal Carcinoma in Histological Images of Breast Cancer.}, journal = {Studies in health technology and informatics}, volume = {290}, number = {}, pages = {587-591}, doi = {10.3233/SHTI220145}, pmid = {35673084}, issn = {1879-8365}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal ; Female ; Humans ; Neural Networks, Computer ; Semantics ; }, abstract = {This paper presents a deep learning approach for automatic detection and visual analysis of Invasive Ductal Carcinoma (IDC) tissue regions. The method proposed in this work is a convolutional neural network (CNN) for visual semantic analysis of tumor regions for diagnostic support. Detection of IDC is a time-consuming and challenging task, mainly because a pathologist needs to examine large tissue regions to identify areas of malignancy. Deep Learning approaches are particularly suitable for dealing with this type of problem, especially when many samples are available for training, ensuring high quality of the learned features by the classifier and, consequently, its generalization capacity. A 3-hidden-layer CNN with data balancing reached both accuracy and F1-Score of 0.85 and outperforming other approaches from the literature. Thus, the proposed method in this article can serve as a support tool for the identification of invasive breast cancer.}, } @article {pmid35672838, year = {2022}, author = {Bhaludin, BN and Tunariu, N and Senthivel, N and Babiker, A and Soneji, ND and Hujairi, N and Sharma, B and McGrath, SE and Okines, AF and Ring, AE and Messiou, C and Downey, K and Koh, DM}, title = {Does the addition of whole-body MRI to routine imaging influence real-world treatment decisions in metastatic breast cancer?.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {22}, number = {1}, pages = {26}, pmid = {35672838}, issn = {1470-7330}, mesh = {*Breast Neoplasms/diagnostic imaging ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/methods ; Positron Emission Tomography Computed Tomography/methods ; Positron-Emission Tomography/methods ; Retrospective Studies ; Whole Body Imaging/methods ; }, abstract = {BACKGROUND: The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC.

METHODS: MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated.

RESULTS: There were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone. 81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%). 24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone. SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC).

CONCLUSIONS: The use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further.}, } @article {pmid35666369, year = {2022}, author = {Utsunomiya, T and Funamizu, N and Ozaki, E and Tamura, K and Sakamoto, K and Ogawa, K and Kusakabe, K and Suehiro, S and Yamashita, D and Kurata, M and Kitazawa, R and Takada, Y}, title = {A case of radical resection for brain metastases of pancreatic cancer after curative chemotherapy for para-aortic lymph node metastases.}, journal = {Surgical case reports}, volume = {8}, number = {1}, pages = {108}, pmid = {35666369}, issn = {2198-7793}, abstract = {BACKGROUND: The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood-brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature.

CASE PRESENTATION: A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors.

CONCLUSIONS: Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.}, } @article {pmid35666367, year = {2022}, author = {Zhang, Y and Luo, X and Chen, M and Yang, L and Lei, T and Pu, T and Wei, B and Bu, H and Zhang, Z}, title = {Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.}, journal = {Breast cancer research and treatment}, volume = {194}, number = {2}, pages = {279-295}, pmid = {35666367}, issn = {1573-7217}, support = {2022YFS0376//Department of Science and Technology of Sichuan Province/ ; }, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; }, abstract = {PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.

METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.

RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67 > 20% tumors (P < 0.05). P-ILCs were subdivided into ER+ (63.1%), HER2+ (21.1%) and TN (15.8%). ER+ P-ILCs were mainly showed trabecular and solid growth patterns. Apocrine and solid features were more strongly associated with HER2+ P-ILCs and TN-P-ILCs, respectively. The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had worse prognosis than the same subtypes in the IDC group, while there was no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC had the worst prognosis. Bone was the most common metastatic site in ER+ P-ILCs and TN-P-ILCs. HER2+ P-ILCs tended to metastasize to the brain and liver. DFS of HER2+ P-ILCs and TN-P-ILCs were worse than that of ER+ P-ILCs. Lacking lobular carcinoma in situ and sTILs ≤ 10% were associated with worse survival of ER+ P-ILCs and TN-P-ILCs, respectively. For HER2+ P-ILCs, Ki-67 > 20% and sTILs ≤ 10% were significant factors for lower DFS.

CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.}, } @article {pmid35665642, year = {2022}, author = {Elangovan, A and Hooda, J and Savariau, L and Puthanmadhomnarayanan, S and Yates, ME and Chen, J and Brown, DD and McAuliffe, PF and Oesterreich, S and Atkinson, JM and Lee, AV}, title = {Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma.}, journal = {Molecular cancer research : MCR}, volume = {20}, number = {9}, pages = {1405-1419}, pmid = {35665642}, issn = {1557-3125}, support = {F30 CA250167/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA224909/CA/NCI NIH HHS/United States ; R01 CA252378/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/pathology ; Cadherins/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; Receptor, IGF Type 1/genetics/metabolism ; Signal Transduction ; }, abstract = {UNLABELLED: No special-type breast cancer [NST; commonly known as invasive ductal carcinoma (IDC)] and invasive lobular carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the IGF1R and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling that thus alters their sensitivity to growth factor-signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediated CDH1 knockout (CDH1 KO) IDC cell lines (MCF7, T47D, and ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation. CDH1 KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and collagen I. CDH1 KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wild-type (WT) and CDH1 KO cells, significantly higher ligand-receptor interaction was observed in the CDH1 KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt, and MEK inhibitors was observed in CDH1 KO cells and ILC patient-derived organoids.

IMPLICATIONS: Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.}, } @article {pmid35664741, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Prediction Breast Molecular Typing of Invasive Ductal Carcinoma Based on Dynamic Contrast Enhancement Magnetic Resonance Imaging Radiomics Characteristics: A Feasibility Study.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {799232}, pmid = {35664741}, issn = {2234-943X}, abstract = {OBJECTIVE: To investigate the feasibility of radiomics in predicting molecular subtype of breast invasive ductal carcinoma (IDC) based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI).

METHODS: A total of 303 cases with pathologically confirmed IDC from January 2018 to March 2021 were enrolled in this study, including 223 cases from Fudan University Shanghai Cancer Center (training/test set) and 80 cases from Shaoxing Central Hospital (validation set). All the cases were classified as HR+/Luminal, HER2-enriched, and TNBC according to immunohistochemistry. DCE-MRI original images were treated by semi-automated segmentation to initially extract original and wavelet-transformed radiomic features. The extended logistic regression with least absolute shrinkage and selection operator (LASSO) penalty was applied to identify the optimal radiomic features, which were then used to establish predictive models combined with significant clinical risk factors. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis were adopted to evaluate the effectiveness and clinical benefit of the models established.

RESULTS: Of the 223 cases from Fudan University Shanghai Cancer Center, HR+/Luminal cancers were diagnosed in 116 cases (52.02%), HER2-enriched in 71 cases (31.84%), and TNBC in 36 cases (16.14%). Based on the training set, 788 radiomic features were extracted in total and 8 optimal features were further identified, including 2 first-order features, 1 gray-level run length matrix (GLRLM), 4 gray-level co-occurrence matrices (GLCM), and 1 3D shape feature. Three multi-class classification models were constructed by extended logistic regression: clinical model (age, menopause, tumor location, Ki-67, histological grade, and lymph node metastasis), radiomic model, and combined model. The macro-average areas under the ROC curve (macro-AUC) for the three models were 0.71, 0.81, and 0.84 in the training set, 0.73, 0.81, and 0.84 in the test set, and 0.76, 0.82, and 0.83 in the validation set, respectively.

CONCLUSION: The DCE-MRI-based radiomic features are significant biomarkers for distinguishing molecular subtypes of breast cancer noninvasively. Notably, the classification performance could be improved with the fusion analysis of multi-modal features.}, } @article {pmid35662504, year = {2022}, author = {Lone, Z and Benidir, T and Rainey, M and Nair, M and Davicioni, E and Gibb, EA and Williamson, S and Gupta, S and Chaim Ornstein, M and Tendulkar, R and Weight, C and Nguyen, JK and Klein, EA and Mian, OY}, title = {Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.}, journal = {European urology focus}, volume = {8}, number = {6}, pages = {1575-1582}, doi = {10.1016/j.euf.2022.05.005}, pmid = {35662504}, issn = {2405-4569}, support = {L30 CA220908/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Prostate ; *Carcinoma, Intraductal, Noninfiltrating/genetics/surgery ; Genomics ; *Prostatic Neoplasms/genetics/surgery ; }, abstract = {BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.

OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.

We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).

Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.

RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).

CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.

PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.}, } @article {pmid35661214, year = {2022}, author = {Sulaj, A and Kopf, S and von Rauchhaupt, E and Kliemank, E and Brune, M and Kender, Z and Bartl, H and Cortizo, FG and Klepac, K and Han, Z and Kumar, V and Longo, V and Teleman, A and Okun, JG and Morgenstern, J and Fleming, T and Szendroedi, J and Herzig, S and Nawroth, PP}, title = {Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {107}, number = {8}, pages = {2167-2181}, pmid = {35661214}, issn = {1945-7197}, support = {236360313-SFB 1118//German Research Foundation/ ; //Deutsches Zentrum für Diabetesforschung/ ; 82DZD07C2G//Diabetes Research/ ; 236360313-SFB 1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Albuminuria/etiology ; Biomarkers ; Creatinine ; DNA/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetic Nephropathies/etiology ; Fasting ; Humans ; *Insulin Resistance ; Lipids ; Receptors, Urokinase Plasminogen Activator ; }, abstract = {CONTEXT: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.

OBJECTIVE: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.

DESIGN/PARTICIPANTS: Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.

MAIN OUTCOMES MEASURES: Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.

RESULTS: FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [-30.3 (-35.7, -24.9) mg/g; P ≤ 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [-3.8 (-5.6, -2.0); P ≤ 0.05] and soluble urokinase plasminogen activator receptor [-156.6 (-172.9, -140.4) pg/mL; P ≤ 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [-1.9 (-3.7, -0.1), P ≤ 0.05]) was sustained.

CONCLUSIONS: Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.}, } @article {pmid35659767, year = {2022}, author = {Wetzel, CL and Gardiner, SK and Johnson, N and Garreau, JR and Sutton, TL}, title = {Variation in adoption of skin and nipple sparing mastectomy: An opportunity to enhance patient outcomes.}, journal = {American journal of surgery}, volume = {224}, number = {2}, pages = {710-715}, doi = {10.1016/j.amjsurg.2022.05.020}, pmid = {35659767}, issn = {1879-1883}, mesh = {*Breast Neoplasms/pathology/surgery ; Female ; Humans ; *Mammaplasty ; Mastectomy ; *Mastectomy, Subcutaneous ; Nipples/pathology/surgery ; Organ Sparing Treatments ; Retrospective Studies ; }, abstract = {BACKGROUND: Nipple-sparing mastectomies (NSM) for breast cancer are under-utilized. We sought to investigate NSM utilization.

METHODS: Females with nonmetastatic breast cancer undergoing mastectomy in the Legacy Health System from 2007 to 2020 were identified. Multivariable logistic regression was utilized to evaluate odds of receiving NSM.

RESULTS: Three-thousand-four-hundred-seventeen mastectomies were performed with 772 undergoing NSM. On multivariable analysis, later year (OR 1.22/year, P < 0.001), neoadjuvant chemotherapy (OR 1.33, P = 0.04), HR+ (OR 1.61, P = 0.001) and surgeon volume (OR 1.16/10 yearly mastectomies, P < 0.001) were independently associated with increased odds of receiving a NSM while age (OR 0.94/year, P < 0.001), IDC (OR 0.58, P = 0.01), T3/T4 stage (OR 0.36, P = 0.009), and clinical node positivity (OR 0.63, P = 0.003) were independently associated with decreased odds. Surgeon volume was not associated with odds of receiving a non-NSM with reconstruction (OR 1.01 P = 0.48).

CONCLUSION: NSM is under-utilized by low-volume breast surgeons. Understanding barriers to adoption is an is an opportunity to enhance patient-centered outcomes.}, } @article {pmid35647336, year = {2022}, author = {Hamed, MM and Gouida, MS and Abd El-Aziz, SR and El-Sokkary, AMA}, title = {Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.}, journal = {Heliyon}, volume = {8}, number = {5}, pages = {e09474}, pmid = {35647336}, issn = {2405-8440}, abstract = {BACKGROUND: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.

METHODS: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.

RESULTS: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p˂0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.

CONCLUSION: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.}, } @article {pmid35646630, year = {2022}, author = {Ruan, M and Ding, Z and Shan, Y and Pan, S and Shao, C and Xu, W and Zhen, T and Pang, P and Shen, Q}, title = {Radiomics Based on DCE-MRI Improved Diagnostic Performance Compared to BI-RADS Analysis in Identifying Sclerosing Adenosis of the Breast.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {888141}, pmid = {35646630}, issn = {2234-943X}, abstract = {PURPOSE: Sclerosing adenosis (SA) is a benign lesion that could mimic breast carcinoma and be evaluated as malignancy by Breast Imaging-Reporting and Data System (BI-RADS) analysis. We aimed to construct and validate the performance of radiomic model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) compared to BI-RADS analysis to identify SA.

METHODS: Sixty-seven patients with invasive ductal carcinoma (IDC) and 58 patients with SA were included in this retrospective study from two institutions. The 125 patients were divided into a training cohort (n= 88) from institution I and a validation cohort from institution II (n=37). Dynamic contrast-enhanced sequences including one pre-contrast and five dynamic post-contrast series were obtained for all cases with different 3T scanners. Single-phase enhancement, multi-phase enhancement, and dynamic radiomic features were extracted from DCE-MRI. The least absolute shrinkage and selection operator (LASSO) logistic regression and cross-validation was performed to build the radscore of each single-phase enhancement and the final model combined multi-phase and dynamic radiomic features. The diagnostic performance of radiomics was evaluated by receiver operating characteristic (ROC) analysis and compared to the performance of BI-RADS analysis. The classification performance was tested using external validation.

RESULTS: In the training cohort, the AUCs of BI-RADS analysis were 0.71 (95%CI [0.60, 0.80]), 0.78 (95%CI [0.67, 0.86]), and 0.80 (95%CI [0.70, 0.88]), respectively. In single-phase analysis, the second enhanced phase radiomic signature achieved the highest AUC of 0.88 (95%CI [0.79, 0.94]) in distinguishing SA from IDC. Nine multi-phase radiomic features and two dynamic radiomic features showed the best predictive ability for final model building. The final model improved the AUC to 0.92 (95%CI [0.84, 0.97]), and showed statistically significant differences with BI-RADS analysis (p<0.05 for all). In the validation cohort, the AUC of the final model was 0.90 (95%CI [0.75, 0.97]), which was higher than all BI-RADS analyses and showed statistically significant differences with one of the BI-RADS analysis observers (p = 0.03).

CONCLUSIONS: Radiomics based on DCE-MRI could show better diagnostic performance compared to BI-RADS analysis in differentiating SA from IDC, which may contribute to clinical diagnosis and treatment.}, } @article {pmid35645339, year = {2022}, author = {Engelhard, CA and Huang, C and Khani, S and Kasparek, P and Prochazka, J and Rozman, J and Reguera, DP and Sedlacek, R and Kornfeld, JW}, title = {Comprehensive Transcriptional Profiling and Mouse Phenotyping Reveals Dispensable Role for Adipose Tissue Selective Long Noncoding RNA Gm15551.}, journal = {Non-coding RNA}, volume = {8}, number = {3}, pages = {}, pmid = {35645339}, issn = {2311-553X}, support = {675014/ERC_/European Research Council/International ; 00000//Danish Diabetes Academy/ ; NNF18OC0033444//Novo Nordisk Foundation/ ; }, abstract = {Cold and nutrient-activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via the uncoupled respiration and secretion of endocrine factors, thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine-tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive. We identified lncRNAs correlating to interscapular brown adipose tissue (iBAT) function in a high fat diet (HFD) and cold stressed mice. We focused on Gm15551, which has an adipose tissue specific expression profile, is highly upregulated during adipogenesis, and downregulated by β-adrenergic activation in mature adipocytes. Although we performed comprehensive transcriptional and adipocyte physiology profiling in vitro and in vivo, we could not detect an effect of gain or loss of function of Gm15551.}, } @article {pmid35639416, year = {2022}, author = {Schwartz-Lifshitz, M and Hertz-Palmor, N and Dekel, I and Balan-Moshe, L and Mekori-Domachevsky, E and Weisman, H and Kaufman, S and Gothelf, D and Amichai-Hamburger, Y}, title = {Loneliness and Social Media Use Among Adolescents with Psychiatric Disorders.}, journal = {Cyberpsychology, behavior and social networking}, volume = {25}, number = {6}, pages = {392-397}, doi = {10.1089/cyber.2021.0337}, pmid = {35639416}, issn = {2152-2723}, mesh = {Adolescent ; Child ; Humans ; Loneliness/psychology ; *Mental Disorders ; Peer Group ; *Social Media ; Social Support ; }, abstract = {Studies have demonstrated that a prolonged feeling of loneliness is a major risk factor for psychopathology among children and adolescents. The purpose of this study was to evaluate the association between patterns of social media use with loneliness and psychopathology among 65 adolescents who were diagnosed with psychiatric disorders and treated at a psychiatric outpatient clinic in Israel. Social capital (online and offline) was negatively associated with loneliness. There was no association between loneliness and patterns of social media use, age, gender, psychiatric diagnosis, or disease severity. Our findings indicate that both online and offline social capital are associated with loneliness, and highlight the importance of studying the effect of peer online social support in alleviating loneliness.}, } @article {pmid35636977, year = {2022}, author = {Groheux, D}, title = {FDG-PET/CT for Primary Staging and Detection of Recurrence of Breast Cancer.}, journal = {Seminars in nuclear medicine}, volume = {52}, number = {5}, pages = {508-519}, doi = {10.1053/j.semnuclmed.2022.05.001}, pmid = {35636977}, issn = {1558-4623}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Neoplasm Recurrence, Local/diagnostic imaging/pathology ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; }, abstract = {Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate baseline staging is necessary to plan optimal breast cancer management. Early detection and staging of recurrence are also essential for optimal therapeutic management. Hybrid FDG-PET/CT imaging offers high sensitivity in detecting extra axillary lymph nodes and distant metastases. Although FDG-PET/CT has some limitations for low proliferative tumors, low-grade tumors and for well-differentiated luminal breast cancer, PET/CT is useful for the initial staging of breast cancer, regardless of tumor phenotype (luminal, triple negative, or HER2+) and of tumor grade. Although FDG-PET/CT performs better for invasive ductal carcinoma (invasive carcinoma of no specific subtype), it is also helpful for staging invasive lobular carcinomas. At initial staging, FDG-PET/CT becomes very useful for staging from clinical stage IIB (T2N1 or T3N0). FDG-PET/CT could be useful in patients with clinical stage IIA (T1N1 or T2N0), but there is not enough strong evidence to recommend routine use in this subgroup. For clinical stage I (T1N0) patients, FDG-PET/CT offers no added value. In patients with recurrent breast cancer, FDG-PET/CT is more effective than conventional imaging in detecting locoregional or distant recurrence, whether suspected by clinical examination, conventional imaging, or elevation of a tumor marker (CA 15.3 or CEA). PET/CT is effective even in the presence of normal tumor markers. PET/CT is also a powerful imaging modality for performing a whole-body workup of a known recurrence and for determining whether or not the recurrence is isolated.}, } @article {pmid35636710, year = {2022}, author = {Willemsen, N and Arigoni, I and Studencka-Turski, M and Krüger, E and Bartelt, A}, title = {Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.}, journal = {Molecular metabolism}, volume = {62}, number = {}, pages = {101518}, pmid = {35636710}, issn = {2212-8778}, mesh = {Adipocytes, Brown/metabolism ; *Adipogenesis/genetics ; Animals ; Inflammation/metabolism ; *Lipodystrophy/metabolism ; Mice ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.

METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.

RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.

CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.}, } @article {pmid35636516, year = {2022}, author = {Akin-Sari, B and Inozu, M and Haciomeroglu, AB and Trak, E and Tufan, D and Doron, G}, title = {Cognitive training using a mobile app as a coping tool against COVID-19 distress: A crossover randomized controlled trial.}, journal = {Journal of affective disorders}, volume = {311}, number = {}, pages = {604-613}, pmid = {35636516}, issn = {1573-2517}, mesh = {Adaptation, Psychological ; *COVID-19 ; Cognition ; Cross-Over Studies ; Female ; Humans ; *Mobile Applications ; Pandemics ; }, abstract = {BACKGROUND: The COVID-19 pandemic has been suggested to constitute a broad base stressor with severe mental health consequences. mHealth applications are accessible self-help tools that can be used to reduce psychological distress during the pandemic. This randomized controlled trial evaluated the effects of mobile-based cognitive training exercises on COVID-19 related distress and maladaptive cognitions.

METHODS: Following initial screening (n = 924), participants scoring 1 standard deviations above the mean of the COVID-19 Distress Scale were randomized into two groups. Participants in the immediate-app group (iApp; n = 25) started using the application at baseline (T0) for 12 days (from T0 to T1). Participants in the delayed-app group (dApp; n = 22) started using the mobile application at T1 (crossover) and used it for the following 12 days (T1 to T2).

RESULTS: Intention to treat analyses indicated that the iApp group exhibited lower COVID-19 distress, lower depression, fewer intolerance of uncertainty and obsessive beliefs than the dApp group at T1. In addition, using the app for 12 consecutive days was associated with large effect-size reductions (Cohen's d ranging from 0.81 to 2.35) in COVID-19 distress and related maladaptive cognitions in the iApp group (from T0 to T1) and the dApp group (from T1 to T2). Moreover, these reductions were maintained at the follow-up.

LIMITATIONS: This study was a crossover trial with a relatively limited sample size and mainly female participants.

CONCLUSION: Our findings underscore the usefulness of brief, low-intensity, portable interventions in alleviating the negative effects of the pandemic on mental health.}, } @article {pmid35625777, year = {2022}, author = {Yu, JM and Chen, LY and Pan, MC and Hsu, YF and Pan, MC and Lin, YL and Sun, SY and Chou, CC}, title = {In Vivo Validation of Diffuse Optical Imaging with a Dual-Direction Measuring Module of Parallel-Plate Architecture for Breast Tumor Detection.}, journal = {Biomedicines}, volume = {10}, number = {5}, pages = {}, pmid = {35625777}, issn = {2227-9059}, support = {MOST 105-2221-E-008-045//Ministry of Science and Technology/ ; MOST 105-2221-E236-005//Ministry of Science and Technology/ ; NCU-LSH-110-B-00//Landseed International Hospital/ ; }, abstract = {We demonstrate a working prototype of an optical breast imaging system involving parallel-plate architecture and a dual-direction scanning scheme designed in combination with a mammography machine; this system was validated in a pilot study to demonstrate its application in imaging healthy and malignant breasts in a clinical environment. The components and modules of the self-developed imaging system are demonstrated and explained, including its measuring architecture, scanning mechanism, and system calibration, and the reconstruction algorithm is presented. Additionally, the evaluation of feature indices that succinctly demonstrate the corresponding transmission measurements may provide insight into the existence of malignant tissue. Moreover, five cases are presented including one subject without disease (a control measure), one benign case, one suspected case, one invasive ductal carcinoma, and one positive case without follow-up treatment. A region-of-interest analysis demonstrated significant differences in absorption between healthy and malignant breasts, revealing the average contrast between the abnormalities and background tissue to exceed 1.4. Except for ringing artifacts, the average scattering property of the structure densities was 0.65-0.85 mm[-1].}, } @article {pmid35621626, year = {2022}, author = {Cho, YA and Ko, SY and Suh, YJ and Kim, S and Park, JH and Park, HR and Seo, J and Choi, HG and Kang, HS and Lim, H and Park, HY and Kwon, MJ}, title = {PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.}, journal = {Current oncology (Toronto, Ont.)}, volume = {29}, number = {5}, pages = {2895-2908}, pmid = {35621626}, issn = {1718-7729}, mesh = {*Asian People/genetics ; B7-H1 Antigen/metabolism ; *Breast Neoplasms/drug therapy/genetics/surgery ; Chemotherapy, Adjuvant ; *Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Prognosis ; }, abstract = {Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.}, } @article {pmid35620494, year = {2022}, author = {Wang, X and Mathews, A and Erickson, A and Veselack, T and Bucholz, E and Vandevender, D and Godellas, C and Vaince, F}, title = {Single Center Oncoplastic Experience and Patient Satisfaction Reported via Patient Reported Outcomes.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {10}, number = {5}, pages = {e4336}, pmid = {35620494}, issn = {2169-7574}, abstract = {UNLABELLED: Oncoplastic breast surgery (OPS) is gaining in popularity compared with traditional breast conserving surgery due to wider resections and better satisfaction with cosmetic outcomes. This study analyzed OPS versus traditional breast conserving surgery outcomes: wound complications, reoperations for margins or fat necrosis, and ipsilateral recurrence.

METHODS: This retrospective review compared 191 OPS and traditional breast conserving surgery patients on patient-related factors, primary outcomes, and patient reported outcome measures results. A propensity score method analysis using 1:1 to nearest neighbor was also performed.

RESULTS: OPS patients were younger, less likely to be smokers, more likely to be ER+ and PR+, and had larger specimen volumes than did traditional breast conserving surgery patients (P < 0.05). There were also differences in distribution of invasive ductal carcinoma and noninvasive disease (P < 0.05). After the propensity score method, the differences observed between the cohorts disappeared. No differences were observed between groups for wound complication, reoperation for positive margins or fat necrosis, or ipsilateral recurrence. Results of patient reported outcome measures showed greater satisfaction with breast surgery in OPS patients (P < 0.01).

CONCLUSIONS: We showed that OPS is a noninferior technique that should be discussed with appropriate patients. Operative planning should involve patient preferences in optimizing long-term cosmetic outcomes.}, } @article {pmid35619675, year = {2022}, author = {Belzer, A and McNiff, JM and Leventhal, JS}, title = {Skin eruption involving bilateral breasts following radiation therapy for invasive ductal carcinoma of the left breast.}, journal = {International journal of women's dermatology}, volume = {8}, number = {2}, pages = {e016}, pmid = {35619675}, issn = {2352-6475}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, } @article {pmid35615799, year = {2022}, author = {Zhang, ML and Wang, X and Xing, ZY and Liu, JQ and Wang, X}, title = {[Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {44}, number = {5}, pages = {425-429}, doi = {10.3760/cma.j.cn112152-20200827-00771}, pmid = {35615799}, issn = {0253-3766}, support = {D161100000816003//Beijing Municipal Scientific and Technical Commission Project/ ; 2016-12M-1-001, 2017-12M-3-004//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Adult ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Ki-67 Antigen ; Lymphatic Metastasis ; *Paget's Disease, Mammary/metabolism ; Prognosis ; Retrospective Studies ; }, abstract = {Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.}, } @article {pmid35610436, year = {2022}, author = {Artati, A and Prehn, C and Lutter, D and Dyar, KA}, title = {Untargeted and Targeted Circadian Metabolomics Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Flow Injection-Electrospray Ionization-Tandem Mass Spectrometry (FIA-ESI-MS/MS).}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2482}, number = {}, pages = {311-327}, pmid = {35610436}, issn = {1940-6029}, mesh = {*Body Fluids ; Chromatography, Liquid/methods ; Metabolomics/methods ; Spectrometry, Mass, Electrospray Ionization/methods ; *Tandem Mass Spectrometry/methods ; }, abstract = {A diverse array of 24-h oscillating hormones and metabolites direct and reflect circadian clock function. Circadian metabolomics uses advanced high-throughput analytical chemistry techniques to comprehensively profile these small molecules (<1.5 kDa) across 24 h in cells, media, body fluids, breath, tissues, and subcellular compartments. The goals of circadian metabolomics experiments are often multifaceted. These include identifying and tracking rhythmic metabolic inputs and outputs of central and peripheral circadian clocks, quantifying endogenous free-running period, monitoring relative phase alignment between clocks, and mapping pathophysiological consequences of clock disruption or misalignment. Depending on the particular experimental question, samples are collected under free-running or entrained conditions. Here we describe both untargeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow injection-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS) based assays we have used for circadian metabolomics studies. We discuss tissue homogenization, chemical derivatization, measurement, and tips for data processing, normalization, scaling, how to handle outliers, and imputation of missing values.}, } @article {pmid35606411, year = {2022}, author = {Shah, RB and Palsgrove, DN and Desai, NB and Gagan, J and Mennie, A and Raj, G and Hannan, R}, title = {Enrichment of "Cribriform" morphologies (intraductal and cribriform adenocarcinoma) and genomic alterations in radiorecurrent prostate cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {35}, number = {10}, pages = {1468-1474}, doi = {10.1038/s41379-022-01093-9}, pmid = {35606411}, issn = {1530-0285}, mesh = {*Adenocarcinoma/genetics/pathology/radiotherapy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Genomics ; Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local/genetics/pathology/radiotherapy ; Prostatectomy ; *Prostatic Neoplasms/genetics/pathology/radiotherapy ; }, abstract = {Locally relapsed prostate cancer (PCa) after radiation therapy (RT) is associated with substantial morbidity and mortality. Morphological and molecular consequences that may contribute to RT resistance and local recurrence remain poorly understood. Locally recurrent PCa tissue from 53 patients with clinically localized PCa who failed with primary RT and subsequently underwent salvage radical prostatectomy (RP) was analyzed for tumor focality, clinicopathological, molecular, and genomic characteristics. Targeted next-generation sequencing with full exon coverage of 1,425 cancer-related genes was performed on 10 representative radiorecurrent PCas exhibiting no RT effect with matched adjacent benign prostate tissue. At RP, 37 (70%) of PCas had no RT effect with the following characteristics: grade group (GG) ≥ 3 (70%), unifocal tumor (75%), extraprostatic disease (78%), lymph node metastasis (8%), and "cribriform" morphologies (84%) [cribriform PCa (78%) or intraductal carcinoma (IDC-P) (61%)] at a median percentage of approximately 80% of tumor volume. In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included: defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.}, } @article {pmid35602239, year = {2022}, author = {de Faria Castro Fleury, E and Castro, C and do Amaral, MSC and Roveda Junior, D}, title = {Management of Non-Mass Enhancement at Breast Magnetic Resonance in Screening Settings Referred for Magnetic Resonance-Guided Biopsy.}, journal = {Breast cancer : basic and clinical research}, volume = {16}, number = {}, pages = {11782234221095897}, pmid = {35602239}, issn = {1178-2234}, abstract = {RATIONALE AND OBJECTIVES: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions.

MATERIALS AND METHODS: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions.

RESULTS: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns.

CONCLUSION: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.}, } @article {pmid35598158, year = {2022}, author = {Iyengar, AS and Ein-Dor, T and Zhang, EX and Chan, SJ and Kaimal, AJ and Dekel, S}, title = {Increased traumatic childbirth and postpartum depression and lack of exclusive breastfeeding in Black and Latinx individuals.}, journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics}, volume = {158}, number = {3}, pages = {759-761}, pmid = {35598158}, issn = {1879-3479}, support = {R21HD100817//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; //Mass General Executive Committee of Research (ECOR)/ ; R21 HD100817/HD/NICHD NIH HHS/United States ; R03 HD101724/HD/NICHD NIH HHS/United States ; R03HD101724//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, mesh = {Breast Feeding ; Depression ; *Depression, Postpartum/epidemiology ; Female ; Humans ; Parturition ; Postpartum Period ; Pregnancy ; *Stress Disorders, Post-Traumatic ; }, } @article {pmid35595629, year = {2023}, author = {Lafcı, O and Celepli, P and Seher Öztekin, P and Koşar, PN}, title = {DCE-MRI Radiomics Analysis in Differentiating Luminal A and Luminal B Breast Cancer Molecular Subtypes.}, journal = {Academic radiology}, volume = {30}, number = {1}, pages = {22-29}, doi = {10.1016/j.acra.2022.04.004}, pmid = {35595629}, issn = {1878-4046}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Ki-67 Antigen ; Receptor, ErbB-2/metabolism ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: The aim of the present study was to investigate the association between Luminal A and Luminal B molecular subtypes and radiomic features of dynamic contrast‑enhanced magnetic resonance imaging in patients with invasive breast cancer.

MATERIALS AND METHODS: Seventy-three patients with histopathologically proven invasive ductal cancer (IDC) were selected. Tumors were classified into molecular subtypes: Luminal A (estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67<20) and Luminal B (ER-positive and/or PR-positive, HER2-positive or HER2-negative with high Ki-67 ≥20). A total of 81 tumoral lesions were evaluated on T1-weighted fat-suppressed sagittal post-contrast late-phase MRI images after the required "pre-process" steps and 3D segmentations were made. Forty-three radiomic features including: 1 conventional, 4 shape, 6 histogram, 7 Grey-Level Co-occurrence Matrix (GLCM), 11 Grey-Level Run-Length Matrix (GLRLM), 3 Neighborhood Grey-Level Difference Matrix (NGLDM), 11 Grey-Level Zone-Length Matrix (GLZLM) were extracted by using the software LIFEX.

RESULTS: A statistically significant difference was found in radiomic features including; a) Histogram: "skewness", b) Shape: "volume-ml, volume-voxel," c) GLCM: "entropy.log10, entropy.log2, energy", d) GLRLM: "GLNU, RLNU, HGRE," e) NGLDM: "busyness," f) GLZLM: "GLNU, HGZE, ZLNU, SZE" between two different molecular subtypes. The model combining Shape-volume (ml) and GLZLM-HGZE yielded 0.746 area under the curve (AUC), 0.744 sensitivity, 0.643 specificity and 0.694 accuracy.

CONCLUSION: Radiomic properties that may distinguish Luminal A and Luminal B molecular subtypes of IDC were identified. The radiomic features were thought to reflect the intratumoral heterogeneity in molecular subtypes. This study demonstrated that the characterization of Luminal A and Luminal B tumors could be made non-invasively by radiomics analysis.}, } @article {pmid35594028, year = {2022}, author = {Koori, N and Miyati, T and Ohno, N and Kawashima, H and Nishikawa, H}, title = {Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.}, journal = {Journal of applied clinical medical physics}, volume = {23}, number = {6}, pages = {e13651}, pmid = {35594028}, issn = {1526-9914}, mesh = {Breast/diagnostic imaging/pathology ; *Breast Neoplasms/pathology ; Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Retrospective Studies ; }, abstract = {Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE-MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype. A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1-min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann-Whitney U-test was used for the statistical analysis. The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A-like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05). The sigmoid model analysis of breast DCE-MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A-like breast cancer.}, } @article {pmid35593951, year = {2023}, author = {Fernandez-Pacheco, M and Ortmann, O and Ignatov, A and Inwald, EC}, title = {Does cavity margin shaving reduce residual tumor and re-excision rates? A systematic review.}, journal = {Archives of gynecology and obstetrics}, volume = {307}, number = {4}, pages = {1295-1309}, pmid = {35593951}, issn = {1432-0711}, mesh = {Humans ; Female ; Neoplasm, Residual/pathology ; Reoperation ; *Breast Neoplasms/surgery/pathology ; Mastectomy, Segmental/methods ; *Plastic Surgery Procedures ; *Carcinoma, Ductal, Breast/pathology/surgery ; Retrospective Studies ; }, abstract = {PURPOSE: Cavity shaving (CS) is a surgical technique used in the treatment of breast cancer (BC). It may reduce margin positivity in histologic assessment and consequently reduces re- excision rates in breast conserving surgery (BCS). The evidence for this assumption is described in the present review.

METHODS: A systematic review of relevant literature in English from January 1999 to April 2019 was conducted. The analysis included studies on CS and its effects on re-excision rates and margin positivity. We searched PubMed databases for relevant publications. In total, 22 studies were included in the present review.

RESULTS: The benefit from CS on re-excision rates and histologic margin positivity was variable. Out of 22 studies, 17 reported a reduction in both re-excision rates and histologic margin positivity in margin shaved patients. Four studies could not find a significant reduction of second surgeries and residual tumor rates. One study suggested that CS after BCS was superior to single BCS only in subgroup analysis in IDC tumors.

CONCLUSION: CS is a surgical technique that was shown to reduce re-excision and margin positivity rates in most of the studies. Furthermore, it can be a useful tool to assess specimen margins and detect multifocality.}, } @article {pmid35592037, year = {2022}, author = {Vincenzi, P and Stronati, M and Isidori, P and Iuorio, S and Gaudenzi, D and Boccoli, G and Starnari, R}, title = {Opioid-Free Segmental Thoracic Spinal Anesthesia with Intrathecal Sedation for Breast and Axillary Surgery: Report of Four Cases.}, journal = {Local and regional anesthesia}, volume = {15}, number = {}, pages = {23-29}, pmid = {35592037}, issn = {1178-7112}, abstract = {PURPOSE: Few studies have described segmental thoracic spinal anesthesia (STSA) as primary anesthesiologic method in breast and axillary surgery, documenting the association of intrathecal local anesthetics and opioids. This case series reports an opioid-free scheme of STSA in four elderly patients undergoing major breast and axillary oncological surgery.

PATIENTS AND METHODS: STSA was performed in three female patients undergoing unilateral mastectomy ± axillary lymph node dissection (ALND) or sentinel lymph node biopsy for invasive ductal carcinoma and in one male patient undergoing ALND for melanoma metastases. The level of needle insertion was included between T6-8, via a median or paramedian approach. Midazolam (2 mg) and ketamine (20 mg) were used as adjuvants for intrathecal sedation, followed by the administration of hypobaric ropivacaine 0.25% at a dose of 8 mg. The level of sensory blockade achieved was comprised between C2-3 and T11-12. Postoperative analgesia was maintained through continuous intravenous administration of Ketorolac by an elastomeric pump (90 mg over 24 hrs.).

RESULTS: Spinal anesthesia was completed without complications in all patients. Conversion to general anesthesia (GA) and perioperative intravenous sedation were not required. No major postoperative complications and no episodes of postoperative nausea and vomiting (PONV) were reported. No rescue analgesic was administered. All patients were discharged in postoperative day 2 and are alive at 30, 29, 27 and 13 months after surgery, respectively. High grade of satisfaction on the anesthesiologic method was expressed by all cases.

CONCLUSION: STSA with local anesthetic plus midazolam and ketamine might be considered a safe and effective alternative to GA, even in surgeries involving the breast and axillary region, particularly in elderly and frail patients. Larger prospective studies are required to validate these findings.}, } @article {pmid35590107, year = {2022}, author = {Bean, GR and Najjar, S and Shin, SJ and Hosfield, EM and Caswell-Jin, JL and Urisman, A and Jones, KD and Chen, YY and Krings, G}, title = {Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {35}, number = {10}, pages = {1349-1361}, pmid = {35590107}, issn = {1530-0285}, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Intraductal, Noninfiltrating ; *Carcinoma, Large Cell/genetics/pathology ; *Carcinoma, Neuroendocrine/pathology ; Carrier Proteins ; Cell Cycle Proteins ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Female ; Humans ; *Neuroendocrine Tumors/pathology ; Proto-Oncogene Proteins/metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.}, } @article {pmid35589277, year = {2022}, author = {Albon, D and Thomas, L and Hoberg, L and Stamper, S and Somerville, L and Varghese, P and Balasa, E and Roman, M and Britto, MT and Miner, M and Gehring, E and Gammon, C and Amin, RS and Seid, M and Powers, M and , }, title = {Cystic fibrosis learning network telehealth innovation lab during the COVID-19 pandemic: a success QI story for interdisciplinary care and agenda setting.}, journal = {BMJ open quality}, volume = {11}, number = {2}, pages = {}, pmid = {35589277}, issn = {2399-6641}, mesh = {*COVID-19 ; *Cystic Fibrosis/therapy ; Humans ; Pandemics ; Quality Improvement ; *Telemedicine/methods ; }, abstract = {INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH.

AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020.

METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform.

RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS.

CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.}, } @article {pmid35587319, year = {2022}, author = {Elisha, E and Guetzkow, J and Shir-Raz, Y and Ronel, N}, title = {Suppressing Scientific Discourse on Vaccines? Self-perceptions of researchers and practitioners.}, journal = {HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues}, volume = {}, number = {}, pages = {1-19}, pmid = {35587319}, issn = {1572-8498}, abstract = {The controversy over vaccines has recently intensified in the wake of the global COVID-19 pandemic, with calls from politicians, health professionals, journalists, and citizens to take harsh measures against so-called "anti-vaxxers," while accusing them of spreading "fake news" and as such, of endangering public health. However, the issue of suppression of vaccine dissenters has rarely been studied from the point of view of those who raise concerns about vaccine safety. The purpose of the present study was to examine the subjective perceptions of professionals (physicians, nurses, researchers) involved with vaccines through practice and/or research and who take a critical view on vaccines, about what they perceive as the suppression of dissent in the field of vaccines, their response to it, and its potential implications on science and medicine. Respondents reported being subjected to a variety of censorship and suppression tactics, including the retraction of papers pointing to vaccine safety problems, negative publicity, difficulty in obtaining research funding, calls for dismissal, summonses to official hearings, suspension of medical licenses, and self-censorship. Respondents also reported on what has been termed a "backfire effect" - a counter-reaction that draws more attention to the opponents' position. Suppression of dissent impairs scientific discourse and research practice while creating the false impression of scientific consensus.}, } @article {pmid35586787, year = {2022}, author = {Leong-Škorničková, J and Böhmová, A and Trần, HĐ}, title = {A new species and new combination in basally flowering Vietnam Costaceae.}, journal = {PhytoKeys}, volume = {190}, number = {}, pages = {103-111}, pmid = {35586787}, issn = {1314-2011}, abstract = {Cheilocostuscandidus sp. nov. (Costaceae), a basally flowering spiral ginger with cream white flowers from southern Vietnam, is described and illustrated here. A new combination, Cheilocostustonkinensis (Gagnep.) Škorničk., is proposed here and the lectotype is designated. A key to Cheilocostus in Vietnam is included.}, } @article {pmid35585552, year = {2022}, author = {Oride, Y and Koi, Y and Sasada, T and Kajitani, K and Ohara, M and Kondo, T and Daimaru, Y and Kawamura, S}, title = {Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.}, journal = {Journal of medical case reports}, volume = {16}, number = {1}, pages = {194}, pmid = {35585552}, issn = {1752-1947}, mesh = {Aged ; *Breast Neoplasms/complications/pathology ; Bronchoscopy/methods ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; *Lung Neoplasms/pathology ; Lymph Nodes/diagnostic imaging/pathology ; *Lymphadenopathy/diagnostic imaging/pathology ; Mastectomy ; Mediastinum/pathology ; Receptors, Interleukin-2 ; *Sarcoidosis/complications/diagnosis/pathology ; }, abstract = {BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.

CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.

CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.}, } @article {pmid35585469, year = {2022}, author = {Ban, K and Tsunoda, H and Togashi, S and Kawakami, M and Takei, J and Kyeongil, K and Inagaki, M}, title = {Comparative study of the usefulness of adjunctive tomosynthesis in breast cancer screening by mammography and ultrasound in Japan.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {29}, number = {5}, pages = {790-795}, pmid = {35585469}, issn = {1880-4233}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Early Detection of Cancer/methods ; Female ; Humans ; Japan/epidemiology ; Mammography/methods ; Mass Screening/methods ; Retrospective Studies ; }, abstract = {INTRODUCTION: There are few studies have conducted digital breast tomosynthesis (DBT) in addition to digital mammography (2DDM) and ultrasound (US) for screening. The purpose of this study is to determine the possibility of synergistic effects of DBT and US screening for Japanese.

METHODS: 5023 examinations of the opportunistic screening using 2DDM and US (2D group: 2581) or 2DDM and US plus DBT (3 group: 2442) were performed at our facility from May 1, 2017 to March 31, 2019. This study was not RCT, and the backgrounds of the two groups were different.

RESULTS: The recall rate was 3.1% in the 2D group and 2.6% for the 3D group (p = 0.27). The number of detected cancer cases was 6 (0.23%) in the 2D group and 12 (0.49%) in the 3D group (p = 0.16). The positive predictive value (PPV) was 7.4% for the 2D group and 19.0% for the 3D group (p = 0.045). There was one invasive ductal carcinoma case which had no findings in 2DDM and US, but had a slight distortion in the images of DBT.

CONCLUSION: We examined and reported whether DBT was useful for breast cancer screening combined with mammography and US. Compared to the 2D group, the 3D group showed better results of PPV with significant difference. However, due to the non-randomized design and difference between the two groups, the results should be interpreted in caution. Adding DBT in 2DDM and US screening would be acceptable only if the benefits and disadvantages are explained to the women undergoing the screening.}, } @article {pmid35578939, year = {2022}, author = {Higashi, T and Ozawa, K and Takei, S and Takagi, S and Yokoyama, M and Mase, K and Moriya, T and Takeshita, A and Mizutani, M}, title = {[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {5}, pages = {581-583}, pmid = {35578939}, issn = {0385-0684}, mesh = {Aged ; Aged, 80 and over ; Aminopyridines ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzimidazoles ; *Breast Neoplasms/drug therapy/pathology/surgery ; Female ; Fulvestrant/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/surgery ; Mastectomy ; Neoplasm Recurrence, Local/surgery ; }, abstract = {A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.}, } @article {pmid35578698, year = {2022}, author = {Aladag Kurt, S and Celik, V}, title = {Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion.}, journal = {Bulletin of the National Research Centre}, volume = {46}, number = {1}, pages = {136}, pmid = {35578698}, issn = {2522-8307}, abstract = {BACKGROUND: The tumor growth pattern in breast cancer appears to be variable and unpredictable. A minor increase in size in a pre-existing lesion, especially under 1 cm, corresponds to a more pronounced increase in volume.

CASE PRESENTATION: We report a 63-year-old woman with a nodular density mimicking intramammary lymph node, diagnosed as invasive carcinoma of luminal B subtype. The lesion increased size and density over time in following mammograms until having indistinct margins. While the tumor volume was 12.7 mm[3] at the first observation on mammography, it has increased approximately 6.7 times to reach 85.7 mm[3] in four years. Finally, the patient diagnosed with early-stage breast cancer (T1N0M0) was treated with breast-conserving surgery.

CONCLUSIONS: Minor changes in size, density, and margin status of a lesion on serial mammograms are warning for breast cancer. Withal, a slight increase in lesion size in two dimensions can result in significant differences in volume. Therefore, comparative evaluation with previous mammograms and observing any difference in morphological features by screening are crucial for early diagnosis and optimal management of the disease.}, } @article {pmid35577875, year = {2022}, author = {Contrepois, K and Chen, S and Ghaemi, MS and Wong, RJ and Jehan, F and Sazawal, S and Baqui, AH and Stringer, JSA and Rahman, A and Nisar, MI and Dhingra, U and Khanam, R and Ilyas, M and Dutta, A and Mehmood, U and Deb, S and Hotwani, A and Ali, SM and Rahman, S and Nizar, A and Ame, SM and Muhammad, S and Chauhan, A and Khan, W and Raqib, R and Das, S and Ahmed, S and Hasan, T and Khalid, J and Juma, MH and Chowdhury, NH and Kabir, F and Aftab, F and Quaiyum, A and Manu, A and Yoshida, S and Bahl, R and Pervin, J and Price, JT and Rahman, M and Kasaro, MP and Litch, JA and Musonda, P and Vwalika, B and , and , and Shaw, G and Stevenson, DK and Aghaeepour, N and Snyder, MP}, title = {Prediction of gestational age using urinary metabolites in term and preterm pregnancies.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8033}, pmid = {35577875}, issn = {2045-2322}, support = {T32 HD075731/HD/NICHD NIH HHS/United States ; R35GM138353/NH/NIH HHS/United States ; OPP1203327/GATES/Bill & Melinda Gates Foundation/United States ; OPP1113682/GATES/Bill & Melinda Gates Foundation/United States ; R35 GM138353/GM/NIGMS NIH HHS/United States ; 2RM1HG00773506/NH/NIH HHS/United States ; T32 HD075731/NH/NIH HHS/United States ; P30AI050410/AI/NIAID NIH HHS/United States ; P30 AI050410/AI/NIAID NIH HHS/United States ; K01 TW010857/TW/FIC NIH HHS/United States ; }, mesh = {Chromatography, Liquid ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Metabolomics ; Pregnancy ; *Ultrasonography, Prenatal ; }, abstract = {Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC-MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value.}, } @article {pmid35576836, year = {2022}, author = {He, S and Jia, Q and Zhou, L and Wang, Z and Li, M}, title = {SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.}, journal = {Pathology, research and practice}, volume = {235}, number = {}, pages = {153943}, doi = {10.1016/j.prp.2022.153943}, pmid = {35576836}, issn = {1618-0631}, mesh = {*Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Glucose/metabolism ; Glycolysis/genetics ; Humans ; *Sirtuins/metabolism/pharmacology ; }, abstract = {OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.

METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500 mg/L) and normal glucose (2000 mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1α, which play roles in aerobic glycolysis, was investigated using western blot.

RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1α caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.

CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.}, } @article {pmid35575162, year = {2022}, author = {Bergman, YS and Palgi, Y and Ben-David, B and Bodner, E}, title = {COVID-19 Vaccinations and Anxiety in Middle-Aged and Older Jews and Arabs in Israel: The Moderating Roles of Ethnicity and Subjective Age.}, journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society}, volume = {41}, number = {8}, pages = {1843-1850}, pmid = {35575162}, issn = {1552-4523}, mesh = {Aged ; Aged, 80 and over ; Anxiety/epidemiology ; Arabs/psychology ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Ethnicity ; Humans ; Israel/epidemiology ; *Jews/psychology ; Middle Aged ; Vaccination ; }, abstract = {Subjective age (i.e., feeling younger/older than one's chronological age) plays a significant role in older minority group members' psychological well-being. In light of the importance of vaccinations for fighting COVID-19, it is unclear whether ethnicity and subjective age moderate the connection between receiving COVID-19 vaccinations and anxiety in Israel. Jewish (n = 198) and Arab older adults (n = 84) provided information regarding COVID-19 vaccinations, subjective age, and anxiety symptoms, as well as additional socio-demographic and COVID-19-related health factors (age range= 40-100, M = 62.5, SD = 12.34). Results demonstrated that feeling older was associated with increased anxiety (p < .001) and that vaccinations were linked to increased anxiety among Jews (p < .05). Moreover, the association between COVID-19 vaccinations and anxiety was significant only among Jewish participants with an older subjective age (p < .05). We stress the importance of examining cultural diversities regarding the contribution of subjective age in the context of COVID-19 and psychological well-being.}, } @article {pmid35567670, year = {2022}, author = {Wilson, GM and Dinh, P and Pathmanathan, N and Graham, JD}, title = {Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {27}, number = {1}, pages = {101-131}, pmid = {35567670}, issn = {1573-7039}, mesh = {Biomarkers ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease Progression ; Female ; Humans ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.}, } @article {pmid35561534, year = {2022}, author = {Shenkman, G}, title = {Winds of change: Will current amendments to Israeli laws discriminating against LGBTQ+ individuals positively affect their mental health?.}, journal = {Psychiatry research}, volume = {313}, number = {}, pages = {114607}, doi = {10.1016/j.psychres.2022.114607}, pmid = {35561534}, issn = {1872-7123}, mesh = {Humans ; Israel ; *Mental Health ; *Sexual and Gender Minorities ; }, } @article {pmid35547416, year = {2022}, author = {Smith, PD and Bhenderu, LS and Kommuri, S and Fleener, EE and Hoover, JM}, title = {Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24008}, pmid = {35547416}, issn = {2168-8184}, abstract = {Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.}, } @article {pmid35546888, year = {2022}, author = {Dor, YI and Algom, D and Shakuf, V and Ben-David, BM}, title = {Age-Related Changes in the Perception of Emotions in Speech: Assessing Thresholds of Prosody and Semantics Recognition in Noise for Young and Older Adults.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {846117}, pmid = {35546888}, issn = {1662-4548}, abstract = {Older adults process emotions in speech differently than do young adults. However, it is unclear whether these age-related changes impact all speech channels to the same extent, and whether they originate from a sensory or a cognitive source. The current study adopted a psychophysical approach to directly compare young and older adults' sensory thresholds for emotion recognition in two channels of spoken-emotions: prosody (tone) and semantics (words). A total of 29 young adults and 26 older adults listened to 50 spoken sentences presenting different combinations of emotions across prosody and semantics. They were asked to recognize the prosodic or semantic emotion, in separate tasks. Sentences were presented on the background of speech-spectrum noise ranging from SNR of -15 dB (difficult) to +5 dB (easy). Individual recognition thresholds were calculated (by fitting psychometric functions) separately for prosodic and semantic recognition. Results indicated that: (1). recognition thresholds were better for young over older adults, suggesting an age-related general decrease across channels; (2). recognition thresholds were better for prosody over semantics, suggesting a prosodic advantage; (3). importantly, the prosodic advantage in thresholds did not differ between age groups (thus a sensory source for age-related differences in spoken-emotions processing was not supported); and (4). larger failures of selective attention were found for older adults than for young adults, indicating that older adults experienced larger difficulties in inhibiting irrelevant information. Taken together, results do not support a sole sensory source, but rather an interplay of cognitive and sensory sources for age-related differences in spoken-emotions processing.}, } @article {pmid35538300, year = {2022}, author = {D'Iorio, A and Baiano, C and Maraucci, G and Vitale, C and Amboni, M and Santangelo, G}, title = {A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {8}, pages = {4605-4609}, pmid = {35538300}, issn = {1590-3478}, mesh = {Aged ; Anhedonia ; *COVID-19 ; Humans ; Longitudinal Studies ; Pandemics ; *Parkinson Disease/complications/diagnosis/epidemiology ; Quality of Life/psychology ; }, abstract = {INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.

METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.

RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z =  - 2.49; p = 0.013; Cohen dz = 0.691. Higher scores of the TEPS total score, Z =  - 2.38; p = 0.025; Cohen dz = 0.621, and LEDD, Z =  - 2.63; p = 0.008; Cohen dz = 0.731, were also reported at T1.

CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.}, } @article {pmid35538223, year = {2022}, author = {Simond, AM and Bui, T and Zuo, D and Sanguin-Gendreau, V and Rao, T and Phillips, WA and Cardiff, RD and Muller, WJ}, title = {Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.}, journal = {Oncogene}, volume = {41}, number = {25}, pages = {3445-3451}, pmid = {35538223}, issn = {1476-5594}, support = {FDN-148373//CIHR/Canada ; }, mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Receptor, ErbB-2/genetics ; }, abstract = {p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110α[HR]) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110α[HR] bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110α[HR] mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.}, } @article {pmid35536810, year = {2023}, author = {Garg, S and Singh, P}, title = {Transfer Learning Based Lightweight Ensemble Model for Imbalanced Breast Cancer Classification.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {2}, pages = {1529-1539}, doi = {10.1109/TCBB.2022.3174091}, pmid = {35536810}, issn = {1557-9964}, mesh = {Reproducibility of Results ; *Neural Networks, Computer ; Machine Learning ; *Neoplasms ; }, abstract = {Automated classification of breast cancer can often save lives, as manual detection is usually time-consuming & expensive. Since the last decade, deep learning techniques have been most widely used for the automatic classification of breast cancer using histopathology images. This paper has performed the binary and multi-class classification of breast cancer using a transfer learning-based ensemble model. To analyze the correctness and reliability of the proposed model, we have used an imbalance IDC dataset, an imbalance BreakHis dataset in the binary class scenario, and a balanced BACH dataset for the multi-class classification. A lightweight shallow CNN model with batch normalization technology to accelerate convergence is aggregated with lightweight MobileNetV2 to improve learning and adaptability. The aggregation output is fed into a multilayer perceptron to complete the final classification task. The experimental study on all three datasets was performed and compared with the recent works. We have fine-tuned three different pre-trained models (ResNet50, InceptionV4, and MobilNetV2) and compared it with the proposed lightweight ensemble model in terms of execution time, number of parameters, model size, etc. In both the evaluation phases, it is seen that our model outperforms in all three datasets.}, } @article {pmid35530044, year = {2022}, author = {Chen, WM and Fu, M and Zhang, CJ and Xing, QQ and Zhou, F and Lin, MJ and Dong, X and Huang, J and Lin, S and Hong, MZ and Zheng, QZ and Pan, JS}, title = {Deep Learning-Based Universal Expert-Level Recognizing Pathological Images of Hepatocellular Carcinoma and Beyond.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {853261}, pmid = {35530044}, issn = {2296-858X}, abstract = {BACKGROUND AND AIMS: We aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types.

METHODS: Microscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation.

RESULTS: In the human-machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively.

CONCLUSION: The performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI's application to diagnoses and treatment recommendations is a promising area for future investigation.}, } @article {pmid35525256, year = {2022}, author = {Weiler, G and Bartovic, J and Ebbesen, BB and Gottardo, C and Puthoopparambil, SJ}, title = {Improving health in immigration detention and promoting alternatives to detention.}, journal = {Lancet (London, England)}, volume = {399}, number = {10338}, pages = {1849-1850}, doi = {10.1016/S0140-6736(22)00742-5}, pmid = {35525256}, issn = {1474-547X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Emigration and Immigration ; Humans ; *Refugees ; }, } @article {pmid35522890, year = {2022}, author = {Butcher, MR and White, MJ and Rooper, LM and Argani, P and Cimino-Mathews, A}, title = {MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {7}, pages = {878-888}, doi = {10.1097/PAS.0000000000001913}, pmid = {35522890}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; In Situ Hybridization ; RNA ; *Salivary Gland Neoplasms/pathology ; *Triple Negative Breast Neoplasms/diagnosis/genetics/pathology ; }, abstract = {Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.}, } @article {pmid35521917, year = {2023}, author = {Kryvenko, ON and Punnen, S and Udayakumar, TS and Gaston, SM and Tao, W and Ma, W and Stoyanova, R and Pollack, A}, title = {Experimental Support for the Possibility of Retrograde Genesis of Intraductal Carcinoma of the Prostate.}, journal = {International journal of surgical pathology}, volume = {31}, number = {2}, pages = {184-189}, doi = {10.1177/10668969221098080}, pmid = {35521917}, issn = {1940-2465}, mesh = {Male ; Humans ; Animals ; Mice ; Prostate/surgery/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Prostatic Intraepithelial Neoplasia/pathology ; Prostate-Specific Antigen ; *Prostatic Neoplasms/pathology ; }, abstract = {Background. Historically, intraductal carcinoma of the prostate (IDC-P) was postulated to be a retrograde spread of high-grade invasive prostate cancer. There is evidence that IDC-P can primarily originate in the prostatic ducts. The retrograde genesis has never been experimentally or clinically confirmed before. Methods. Biopsy proven intermediate or high-risk prostate cancer was orthotopically grafted in the prostate of severe combined immunodeficiency gamma mice. Cancer growth was monitored by serum PSA levels. The animals were sacrificed and grafted areas were histological examined. Results. Twenty-one of 23 mice survived and demonstrated rising serum PSA. In 10 of 21 animals, human prostate cancer was identified orthotopically. Except for one case where the human biopsy showed a Grade Group 2 prostate cancer and mouse graft was Grade Group 5, other 9 specimens showed comparable grades. One of the specimens demonstrated a cribriform invasive prostate cancer and adjacent IDC-P. Conclusion. These experimental data offer some evidence that invasive prostate cancer can demonstrate a retrograde spread in the prostatic ducts as IDC-P. Its ability to primarily arise in the ducts has been demonstrated in other studies. However, the issue which remains unresolved is in its most common presentation of IDC-P intermixed with high-grade invasive cancer if it is the former or the latter which came first. Possibly resolving this dilemma will shed some light on the existing controversies if IDC-P should or should not be graded when invasive cancer is present.}, } @article {pmid35514196, year = {2022}, author = {Aizawa, R and Tsuzuki, T and Haga, H and Nakamura, K and Ogata, T and Inoue, T and Kobayashi, T and Akamatsu, S and Goto, T and Ogawa, O and Mizowaki, T}, title = {Clinical significance of IDC-P as predictive factor after intensity-modulated radiation therapy.}, journal = {Cancer science}, volume = {113}, number = {7}, pages = {2425-2433}, pmid = {35514196}, issn = {1349-7006}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Male ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; *Radiotherapy, Intensity-Modulated ; Retrospective Studies ; }, abstract = {The clinical significance of intraductal carcinoma of the prostate (IDC-P) in men with nonmetastatic prostate cancer (PCa) treated with high-dose external-beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC-P in men who received intensity-modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high-risk (H-R) and very high-risk (VH-R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re-reviewed biopsy cores for the presence of IDC-P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6-month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H-R and VH-R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow-up period was 8.4 years. The 10-year PCa-specific survival, biochemical failure (BF), clinical failure, and castration-resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC-P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC-P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC-P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC-P was correlated with a significantly higher incidence of disease progression in men with H-R and VH-R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC-P as an independent predictive factor for survival outcomes.}, } @article {pmid35513312, year = {2022}, author = {Bruce, MK and Joseph, WJ and Grunwaldt, L and Nguyen, VT and De La Cruz, C}, title = {Transgender Mastectomy: Incidence of High-Risk Pathologic Findings and the Need for Postoperative Cancer Surveillance.}, journal = {Annals of plastic surgery}, volume = {88}, number = {3 Suppl 3}, pages = {S148-S151}, doi = {10.1097/SAP.0000000000003175}, pmid = {35513312}, issn = {1536-3708}, mesh = {Adult ; *Breast Neoplasms/diagnosis/epidemiology/surgery ; Female ; Humans ; Incidence ; Male ; Mastectomy/methods ; Middle Aged ; *Transgender Persons ; *Transsexualism ; }, abstract = {BACKGROUND: Chest masculinization surgeries are one of the most common gender-affirming procedures performed. There is a need for better understanding of the risk of breast cancer and postsurgical screening in female to male (FtM) individuals. This study aimed to evaluate the incidence of high-risk pathologic findings in FtM transgender patients undergoing gender-affirming chest reconstructive surgery.

METHODS: Medical records were reviewed from all FtM patients undergoing gender-affirming chest reconstructive surgery from January 2010 to February 2021 by 3 plastic surgeons at the University of Pittsburgh Medical Center. Relative risk of malignant progression was used to stratify pathologic data. Subsequent management of atypical, in situ, and invasive pathology were recorded.

RESULTS: A total of 318 patients were included in this study; the average age at surgery was 24.6 ± 8.1 years. Eighty-six patients (27%) had a family history of breast and/or ovarian cancer. Overall, 21 patients (6.6%) had some increased risk of breast cancer: 17 (5.3%) had proliferative lesions, mean age 38.2 ± 12.4 years; 2 had atypical ductal hyperplasia, ages 33.4 and 38.3 years; and 2 had invasive ductal carcinoma, ages 35.4 and 40.6 years.

CONCLUSIONS: In this study, we found that 6.6% of FtM transgender patients undergoing top surgery had an elevated risk of breast cancer, with 1.2% of patients having a greater than 2 times risk of breast cancer. These results highlight the importance of appropriate preoperative screening as well as pathological analysis of surgical specimens to help guide clinical care. The authors advocate for a thorough breast cancer risk assessment before surgery for all patients, as well as using pathologic findings to guide postoperative cancer screening and follow-up.}, } @article {pmid35509603, year = {2022}, author = {Tao, Q and Li, X and Zhu, T and Ge, X and Gong, S and Guo, J and Ma, R}, title = {Lactate Transporter SLC16A3 (MCT4) as an Onco-Immunological Biomarker Associating Tumor Microenvironment and Immune Responses in Lung Cancer.}, journal = {International journal of general medicine}, volume = {15}, number = {}, pages = {4465-4474}, pmid = {35509603}, issn = {1178-7074}, abstract = {PURPOSE: Lactate, a marker of tumor metabolic reprogramming, maintains the acidic microenvironment and also affects the metabolism and function of immune cells. SLC16A3 is responsible for the extracellular transport of lactate, which is a key component of glycolysis. However, the role of SLC16A3 in immune infiltration and immunosuppression of lung cancer is largely unknown. Our study explored the therapeutic and prognostic value of SLC16A3 in predicting immune infiltration and immune checkpoint efficacy of lung cancer.

METHODS: SLC16A3 expression was evaluated with TCGA database. Kaplan-Meier analysis was performed for survival rates. GO and KEEG enrichment was conducted to determine predictive signaling pathways. We utilized TIMER and CIBERSORT to analyze the correlation between SLC16A3 and immunocyte infiltration as well as immune checkpoint. Interleukin and HIF-1a expression was measured with ELISA kit and flow cytometry separately.

RESULTS: In comparison with normal tissues, SLC16A3 expression was significantly upregulated in both lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC), which was closely related to poor prognosis. GO analysis indicated that SLC16A3 involved in different signal pathways in LUAD and LUSC and linked to HIF-1 signaling in LUAD. High SLC16A3 was correlated with immunosuppressive cells (Treg, Th2 and iDC), immune checkpoint (PD1, PD-L1, PVR, Tim-3, ITGAM) and immunosuppressive factors (foxp3, TGF-β) in LUAD not LUSC. Furthermore, SLC16A3 was identified to tightly interact with IL-8 which may induce microenvironment immune tolerance. Based on the clinical prediction, we performed experiments with LUAD A549 cells and showed reduced IL-8 and HIF-1a when treated with SLC16A3 knockdown. HIF-1a stimulation by dimethyloxalylglycine (DMOG) could restore IL-8 secretion in SLC16A3 downregulated cells.

CONCLUSION: Taken together, our results suggest that SLC16A3 contributes to a worse prognosis in lung cancer and may play an important role in immune microenvironment and evasion through HIF-1a-IL8 axis, which could be a novel therapeutic target for immunotherapy in lung cancer.}, } @article {pmid35507295, year = {2023}, author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM}, title = {Response to McKenzie et al. 2021: Keep It Simple; Young Adults With Autism Spectrum Disorder Without Intellectual Disability Can Process Basic Emotions.}, journal = {Journal of autism and developmental disorders}, volume = {53}, number = {3}, pages = {1269-1272}, pmid = {35507295}, issn = {1573-3432}, mesh = {Humans ; Young Adult ; *Autism Spectrum Disorder/psychology ; *Intellectual Disability ; Emotions/physiology ; Empathy ; *Autistic Disorder ; }, abstract = {We recently read the interesting and informative paper entitled "Empathic accuracy and cognitive and affective empathy in young adults with and without autism spectrum disorder" (McKenzie et al. in Journal of Autism and Developmental Disorders 52: 1-15, 2021). This paper expands recent findings from our lab (Ben-David in Journal of Autism and Developmental Disorders 50: 741-756, 2020a; International Journal of Audiology 60: 319-321, 2020b) and a recent theoretical framework (Icht et al. in Autism Research 14: 1948-1964, 2021) that may suggest a new purview for McKenzie et al.'s results. Namely, these papers suggest that young adults with autism spectrum disorder without intellectual disability can successfully recruit their cognitive abilities to distinguish between different simple spoken emotions, but may still face difficulties processing complex, subtle emotions. McKenzie et al. (Journal of Autism and Developmental Disorders 52: 1-15, 2021) extended these findings to the processing of emotions in video clips, with both visual and auditory information.}, } @article {pmid35505755, year = {2022}, author = {Latif, S and Perveen, S and Iqbal, M and Ahmed, T and Moula Bux, K and Jafri, SNA}, title = {Epidemiology of Carcinoma Breast in Young Adolescence Women.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23683}, pmid = {35505755}, issn = {2168-8184}, abstract = {Introduction The aim of this study was to compare epidemiological characteristics of breast cancer in young adolescent women (YAW) versus older women (OW). Methods This was a cross-sectional prospective observational study, conducted in Ward 3, Jinnah Postgraduate Medical Center, Karachi, Pakistan, from September 2021 to February 2022. A total of 120 female patients were recruited in this study from the Outpatient Department of Jinnah Postgraduate Medical Center, out of which 22 patients were below the age of 40 years and 98 were above 40 years. For breast cancer diagnosis, we used the triple assessment method involving clinical examination, radiology, and histopathology. Diagnosed patients were further evaluated for hormonal status and metastatic workup. Results were noted on a performa, and differences between both age groups were analyzed. Results Out of 120 patients, 22 were younger than 40 years and 98 were older than 40 years. YAW used to present late after the appearance of symptoms. Patients of both age groups mostly presented with breast lumps (68.18% in YAW and 81.6% in OW). YAW presented with larger sizes of lumps and with more nodal involvement as compared to OW. BI-RADS IV (Breast Imaging Reporting and Data System Category IV) was the most commonly observed (27.27% in YAW and 48.97% in OW) mammographic finding in both age groups. Invasive ductal carcinoma was the most common histological type in both age groups (72.73% in YAW and 76.53% in OW). The triple-negative disease was more commonly found in YAW than OW (40.91% in YAW vs 21.43% in OW). We found that usually YAW presented at advanced stages (stages III and IV, 54.55%) and higher grades (grade III, 63.63%). Conclusion Breast cancer in young patients is rare but more aggressive with higher grades, advanced stages, and poor prognostic features. Heredity is mainly the risk factor in young breast cancer patients. There should be proper screening programs for high-risk group for early diagnosis and prompt treatment. Other age-specific concerns such as psychological impact of disease should be addressed as well.}, } @article {pmid35494985, year = {2022}, author = {Grove, J and Komforti, MK and Craig-Owens, L and Beuerlein, F}, title = {A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23588}, pmid = {35494985}, issn = {2168-8184}, abstract = {Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.}, } @article {pmid35494886, year = {2022}, author = {Kim, DH and Webster, TK and Bartolacci, JG and Araya, S and Panichella, J and Patel, SA}, title = {Use of Needle Localization in the Surgical Management of Non-seroma, Mass-forming BIA-ALCL.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {10}, number = {4}, pages = {e4286}, pmid = {35494886}, issn = {2169-7574}, abstract = {Outcomes related to the treatment of breast implant-associated anaplastic large cell lymphoma, a rare extranodal T-cell lymphoma associated with textured breast implants, are largely dependent on the successful resection to negative margins via en bloc capsulectomy and resection of any associated masses. To date, the use of needle localization, a common technique used in breast surgery, to assist in the complete removal of breast implant-associated anaplastic large cell lymphoma has not been described. We present the case report of a 66-year-old woman, with a previous medical history of left-sided invasive ductal carcinoma, who presented 7 years after textured breast implant placement with a left-sided mass without peri-implant seroma. Biopsy demonstrated breast implant-associated anaplastic large cell lymphoma and the associated breast mass extended beyond the capsule borders. The present report describes the novel use of needle localization in this patient to facilitate the complete removal of the malignancy-associated mass with maximal preservation of the overlying soft tissue envelope.}, } @article {pmid35493781, year = {2022}, author = {Sazawal, S and Das, S and Ryckman, KK and Khanam, R and Nisar, I and Deb, S and Jasper, EA and Rahman, S and Mehmood, U and Dutta, A and Chowdhury, NH and Barkat, A and Mittal, H and Ahmed, S and Khalid, F and Ali, SM and Raqib, R and Ilyas, M and Nizar, A and Manu, A and Russell, D and Yoshida, S and Baqui, AH and Jehan, F and Dhingra, U and Bahl, R}, title = {Machine learning prediction of gestational age from metabolic screening markers resistant to ambient temperature transportation: Facilitating use of this technology in low resource settings of South Asia and East Africa.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {04021}, pmid = {35493781}, issn = {2047-2986}, mesh = {*Dry Ice ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; *Machine Learning ; Pakistan ; Pregnancy ; Tanzania ; Technology ; Temperature ; }, abstract = {BACKGROUND: Knowledge of gestational age is critical for guiding preterm neonatal care. In the last decade, metabolic gestational dating approaches emerged in response to a global health need; because in most of the developing world, accurate antenatal gestational age estimates are not feasible. These methods initially developed in North America have now been externally validated in two studies in developing countries, however, require shipment of samples at sub-zero temperature.

METHODS: A subset of 330 pairs of heel prick dried blood spot samples were shipped on dry ice and in ambient temperature from field sites in Tanzania, Bangladesh and Pakistan to laboratory in Iowa (USA). We evaluated impact on recovery of analytes of shipment temperature, developed and evaluated models for predicting gestational age using a limited set of metabolic screening analytes after excluding 17 analytes that were impacted by shipment conditions of a total of 44 analytes.

RESULTS: With the machine learning model using all the analytes, samples shipped in dry ice yielded a Root Mean Square Error (RMSE) of 1.19 weeks compared to 1.58 weeks for samples shipped in ambient temperature. Out of the 44 screening analytes, recovery of 17 analytes was significantly different between the two shipment methods and these were excluded from further machine learning model development. The final model, restricted to stable analytes provided a RMSE of 1.24 (95% confidence interval (CI) = 1.10-1.37) weeks for samples shipped on dry ice and RMSE of 1.28 (95% CI = 1.15-1.39) for samples shipped at ambient temperature. Analysis for discriminating preterm births (gestational age <37 weeks), yielded an area under curve (AUC) of 0.76 (95% CI = 0.71-0.81) for samples shipped on dry ice and AUC of 0.73 (95% CI = 0.67-0.78) for samples shipped in ambient temperature.

CONCLUSIONS: In this study, we demonstrate that machine learning algorithms developed using a sub-set of newborn screening analytes which are not sensitive to shipment at ambient temperature, can accurately provide estimates of gestational age comparable to those from published regression models from North America using all analytes. If validated in larger samples especially with more newborns <34 weeks, this technology could substantially facilitate implementation in LMICs.}, } @article {pmid35489766, year = {2022}, author = {Chung, Y and Kim, S and Kim, HS and DO, SI}, title = {High Receptor-interacting Serine/Threonine-protein Kinase 3 (RIP3) Expression Serves as an Independent Poor Prognostic Factor for Triple-negative Breast Carcinoma.}, journal = {Anticancer research}, volume = {42}, number = {5}, pages = {2753-2761}, doi = {10.21873/anticanres.15754}, pmid = {35489766}, issn = {1791-7530}, mesh = {Breast/pathology ; Humans ; Prognosis ; Serine ; Threonine ; *Triple Negative Breast Neoplasms/pathology ; }, abstract = {BACKGROUND/AIM: Receptor-interacting serine/threonine-protein kinase 3 (RIP3) is a key component related to tumor necrosis factor-dependent necroptosis. RIP3 has been known to be a predictive biomarker in many types of carcinomas. We aimed to investigate whether RIP3 expression is correlated with clinicopathological characteristics and the outcomes of patients with breast carcinoma.

PATIENTS AND METHODS: We performed immunostaining for RIP3 and analyzed the association of RIP3 expression status with the clinicopathological characteristics and survival of 203 patients with invasive ductal carcinoma of the breast.

RESULTS: High RIP3 expression was significantly correlated with lymph node metastasis and human epidermal growth factor receptor 2 positivity. In patients with triple-negative breast carcinoma (TNBC), high RIP3 expression was an independent prognostic factor for disease-free survival (DFS). RIP3-high TNBC showed the lowest DFS rate.

CONCLUSION: High RIP3 expression is associated with aggressive clinical behavior of breast carcinoma. Our data suggest that RIP3 serves as an independent prognostic factor in TNBC.}, } @article {pmid35478743, year = {2022}, author = {Nitsan, G and Banai, K and Ben-David, BM}, title = {One Size Does Not Fit All: Examining the Effects of Working Memory Capacity on Spoken Word Recognition in Older Adults Using Eye Tracking.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {841466}, pmid = {35478743}, issn = {1664-1078}, abstract = {Difficulties understanding speech form one of the most prevalent complaints among older adults. Successful speech perception depends on top-down linguistic and cognitive processes that interact with the bottom-up sensory processing of the incoming acoustic information. The relative roles of these processes in age-related difficulties in speech perception, especially when listening conditions are not ideal, are still unclear. In the current study, we asked whether older adults with a larger working memory capacity process speech more efficiently than peers with lower capacity when speech is presented in noise, with another task performed in tandem. Using the Eye-tracking of Word Identification in Noise Under Memory Increased Load (E-WINDMIL) an adapted version of the "visual world" paradigm, 36 older listeners were asked to follow spoken instructions presented in background noise, while retaining digits for later recall under low (single-digit) or high (four-digits) memory load. In critical trials, instructions (e.g., "point at the candle") directed listeners' gaze to pictures of objects whose names shared onset or offset sounds with the name of a competitor that was displayed on the screen at the same time (e.g., candy or sandal). We compared listeners with different memory capacities on the time course for spoken word recognition under the two memory loads by testing eye-fixations on a named object, relative to fixations on an object whose name shared phonology with the named object. Results indicated two trends. (1) For older adults with lower working memory capacity, increased memory load did not affect online speech processing, however, it impaired offline word recognition accuracy. (2) The reverse pattern was observed for older adults with higher working memory capacity: increased task difficulty significantly decreases online speech processing efficiency but had no effect on offline word recognition accuracy. Results suggest that in older adults, adaptation to adverse listening conditions is at least partially supported by cognitive reserve. Therefore, additional cognitive capacity may lead to greater resilience of older listeners to adverse listening conditions. The differential effects documented by eye movements and accuracy highlight the importance of using both online and offline measures of speech processing to explore age-related changes in speech perception.}, } @article {pmid35478712, year = {2022}, author = {Xu, M and Li, F and Yu, S and Zeng, S and Weng, G and Teng, P and Yang, H and Li, X and Liu, G}, title = {Value of Histogram of Gray-Scale Ultrasound Image in Differential Diagnosis of Small Triple Negative Breast Invasive Ductal Carcinoma and Fibroadenoma.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {1515-1524}, pmid = {35478712}, issn = {1179-1322}, abstract = {OBJECTIVE: To investigate the value of gray-scale ultrasound (US) image histogram in the differential diagnosis between small (≤2.00 cm), oval, or round triple negative breast invasive ductal carcinoma (TN-IDC) and fibroadenoma (FA).

METHODS: Fifty-five cases of triple negative breast invasive ductal carcinoma (TN-IDC group) and 57 cases of breast fibroadenoma (FA group) confirmed by pathology in Hubei cancer hospital from September 2017 to September 2021 were analyzed retrospectively. The gray-scale US images were analyzed by histogram analysis method, from which some parameters (including mean, variance, skewness, kurtosis and 1st, 10th, 50th, 90th and 99th percentile) can be obtained. Intraclass correlation coefficient (ICC) was used to evaluate the inter observer reliability of histogram parameters. Histogram parameters between the TN-IDC and FA groups were compared using independent Student's t-test or Mann-Whitney U-test, respectively. In addition, the receiver operating characteristic (ROC) curve analysis was used for the significant parameters to calculate the differential diagnosis efficiency.

RESULTS: All the histogram parameters showed excellent inter-reader consistency, with the ICC values ranged from 0.883 to 0.999. The mean value, 1st, 10th, 50th, 90th and 99th percentiles of TN-IDC group were significantly lower than those of FA group (P < 0.05). The area under ROC curve (AUC) values of mean and n percentiles were from 0.807 to 0.848. However, there were no significant differences in variance, skewness and kurtosis between the two groups (P > 0.05).

CONCLUSION: Histogram analysis of gray-scale US images can well distinguish small, oval, or round TN-IDC from FA.}, } @article {pmid35478129, year = {2022}, author = {Salih, MM and Higgo, AA and Khalifa, AS and Eed, EM}, title = {Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {3}, pages = {1513-1518}, pmid = {35478129}, issn = {1791-7549}, mesh = {Adult ; Antibodies, Monoclonal ; *Antineoplastic Agents, Immunological ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal/complications ; *Epstein-Barr Virus Infections/complications/epidemiology/pathology ; Female ; Herpesvirus 4, Human ; Humans ; Incidence ; Male ; Membrane Proteins ; Middle Aged ; Viral Proteins ; }, abstract = {BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.

PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.

RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14±14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.

CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.}, } @article {pmid35477215, year = {2022}, author = {Shah, NR and Pfost, SS and Mao, RD and Klimberg, VS}, title = {Oncoplastic reconstruction of a large chest wall defect using dual fasciocutaneous flaps: A case report.}, journal = {International journal of surgery case reports}, volume = {93}, number = {}, pages = {107010}, pmid = {35477215}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Large chest wall defects in the context of breast cancer or its sequelae can be challenging to address. Oncoplastic techniques have been demonstrated to be safe and feasible options for immediate reconstruction. We describe the use of dual fasciocutaneous flaps for coverage following resection of a large chest wall mass in an area with a remote history of radiation therapy.

CASE PRESENTATION: A 67-year-old woman with a distant history of bilateral mastectomies and adjuvant chemoradiation for Stage IIB triple negative invasive ductal carcinoma presented with an enlarging left chest wall mass and chronic wound. The mass was excised with adequate margins, and the resulting defect was reconstructed with two locoregional fasciocutaneous flaps. Pathology returned negative for malignancy and follow-up demonstrated viable flaps that were healing well.

CLINICAL DISCUSSION: Fasciocutaneous flaps are one of many techniques for breast reconstruction and offer advantages of a relatively superficial dissection, shorter operative time, and decreased risk of functional impairment. They are consequently an attractive option for patients with multiple comorbidities and high risk of perioperative complications. Historically used for immediate reconstruction at the time of oncologic resection, we present its successful use decades after the index cancer operation to manage a chest wall defect secondary to radiation injury.

CONCLUSIONS: Oncoplastic reconstruction with dual fasciocutaneous flaps is a feasible option for a large chest wall defect in the setting of previous radiation.}, } @article {pmid35475284, year = {2022}, author = {Cole, NA and Copeland-Halperin, LR and Shank, N and Shankaran, V}, title = {BRCA2-associated Breast Cancer in Transgender Women: Reconstructive Challenges and Literature Review.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {10}, number = {4}, pages = {e4059}, pmid = {35475284}, issn = {2169-7574}, abstract = {Breast cancer in trans women is rare. Only 21 cases have been reported worldwide. Multidisciplinary teams must balance oncologic treatment with patient goals. Here we describe a case of invasive ductal carcinoma in a transgender woman who was found to have a BRCA2 gene mutation. A shared decision-making process led to the patient undergoing bilateral nipple-sparing mastectomy with immediate tissue expander placement. Later findings prompted discussions about adjuvant chemotherapy and radiation. Additionally, we discuss the complexities associated with reconstructing a transfeminine chest.}, } @article {pmid35472669, year = {2023}, author = {Wang, Y and Teramoto, Y and Weisenthal, SJ and Goto, T and Miyamoto, H}, title = {The Clinical Impact of Comedonecrosis Within Intraductal Carcinoma of the Prostate.}, journal = {Archives of pathology & laboratory medicine}, volume = {147}, number = {1}, pages = {94-99}, doi = {10.5858/arpa.2021-0346-OA}, pmid = {35472669}, issn = {1543-2165}, mesh = {Male ; Humans ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; *Prostatic Neoplasms/pathology ; Neoplasm Grading ; Prostatectomy ; Necrosis ; }, abstract = {CONTEXT.—: Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally present. Meanwhile, assigning a Gleason grade to IDC-P remains controversial.

OBJECTIVE.—: To assess the clinical significance of necrosis associated with IDC-P.

DESIGN.—: We compared radical prostatectomy (RP) findings and oncologic outcomes in men with prostate cancer exhibiting IDC-P with (IDC-P+/N+) versus without (IDC-P+/N-) comedonecrosis.

RESULTS.—: Of the 558 RPs examined, IDC-P was present in 213 cases (38.2%), including 167 (78.4%) with IDC-P+/N- and 46 (21.6%) with IDC-P+/N+. When comparing IDC-P+/N- versus IDC-P+/N+ cases, the presence of necrosis was significantly associated with higher tumor grade, higher incidence of pT3/pT3b or pN1 disease, and larger estimated tumor volume. Outcome analysis revealed a significantly higher risk of disease progression in IDC-P+/N+ patients than in IDC-P+/N- patients (P < .001). Significant differences in progression-free survival between IDC-P+/N- and IDC-P+/N+ patients were also seen in subgroups, such as those without (P = .01) or with (P = .03) adjuvant therapy immediately after RP, those with pN0 disease (P < .001), and, more interestingly, those exhibiting conventional Gleason pattern 5 component (P = .02). Multivariate analysis showed significance for IDC-P+/N+ when IDC-P (grade 4) and IDC-P+/N+ (grade 5) were (hazard ratio, 1.768; P = .049) or were not (hazard ratio, 2.000; P = .008) incorporated into the Gleason score.

CONCLUSIONS.—: IDC-P+/N+ was found to be associated with worse histopathologic features on RP and poorer prognosis as an independent predictor. Pathologists may thus need to report the presence or absence of not only IDC-P but also comedonecrosis within IDC-P.}, } @article {pmid35470542, year = {2022}, author = {Lim, JSH and Sim, Y and Ngeow, J and Yuen, J and Tan, VKM and Tan, BKT and Yong, WS and Wong, CY and Lim, SZ and Hamzah, JLB and Tan, SY and Wong, FY and Madhukumar, P}, title = {Male breast cancer: a Singapore perspective.}, journal = {ANZ journal of surgery}, volume = {92}, number = {6}, pages = {1440-1446}, doi = {10.1111/ans.17737}, pmid = {35470542}, issn = {1445-2197}, mesh = {Axilla/pathology ; *Breast Neoplasms/pathology ; *Breast Neoplasms, Male/epidemiology/surgery ; Disease-Free Survival ; Female ; Humans ; Lymph Node Excision/methods ; Lymphatic Metastasis ; Male ; Mastectomy ; Sentinel Lymph Node Biopsy ; Singapore/epidemiology ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) is rare, representing <1% of all breast cancers. Treatment recommendations have been extrapolated from trial data of female breast cancer patients. This study aims to report our institutional experience of MBC across a 20 year period, analyse the survival outcome and prognosis of this group against female breast cancer patients treated at the same centre.

METHODS: Clinical, histopathological, treatment and survival data of male and female breast cancer patients treated between Jan 1999 and July 2019 at Singapore General Hospital and National Cancer Centre Singapore were identified and analysed.

RESULTS: Fifty-seven male patients were identified. The median age at diagnosis was 63 years. Majority had invasive ductal carcinoma (86%) and presented at an early disease stage: 70.2% presented as Tis/T1/T2 and 49.1% had no axillary nodal involvement. 84.2% had a simple mastectomy with either a sentinel lymph node biopsy or axillary clearance. The median follow up was 5.69 years for males and 5.83 years for females. The median survival was 11.86 years for males and 16.3 years for females. At 5 years, overall survival (OS) was 69.9% (52.3-82.1%) and disease free survival (DFS) was 62.9% (44.9-76.5%) for males compared with OS 83.8% (83.21-84.39%) and DFS 74.5% (73.91-75.09%) for females.

CONCLUSION: MBC remains understudied. Our institutional data indicates that good long term survival in South-East Asian patients can be achieved with treatment protocols that are similar to female breast cancer. More prospective studies are required.}, } @article {pmid35466619, year = {2022}, author = {Shamsi, FB and Anwar, A and Lail, RA and Bukhari, MH and Naseem, N and Nagi, AH}, title = {Immunohistochemical Expression Of Matrix Metalloproteinase-1 (MMP-1) in Different Types Of Breast Carcinoma And Its Comparison With ER/PER and HER2/neu.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {34}, number = {1}, pages = {12-16}, doi = {10.55519/JAMC-01-8189}, pmid = {35466619}, issn = {1819-2718}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/pathology ; Female ; Humans ; Mastectomy ; Matrix Metalloproteinase 1/*metabolism ; Middle Aged ; Receptor, ErbB-2 ; Receptors, Estrogen/metabolism ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Breast cancer is a complex disease that comprises of various biological sub-types with different natural history. Matrix metalloproteinase-1(MMP-1) expression has been reported to inversely correlate with the survival. The current study was conducted to classify breast cancer into four subtypes based on IHC, to assess the immunohistochemical expression of MMP-1 in primary breast carcinoma, to compare its expression with ER/PR and HER2/neu.

METHODS: A descriptive study was conducted on 100 mastectomy specimens of breast carcinoma after being fixed in 10% formalin at Department of Histopathology, University of Health Sciences Lahore. Sections were taken on frosted slides for H&E and on lysine coated slides for immunohistochemistry (IHC). Haematoxylin and eosin (H&E) and IHC for oestrogen receptor/progesterone receptor (ER/PR), HER2/neu and Matrix metalloproteinase (MMP-1) were performed according to protocol.

RESULTS: The mean age was 48.4411.79 Years (ranging 25 to 90 years). 97 cases were of Invasive ductal carcinoma (IDC) type, two showed the features of invasive lobular carcinoma and only one case was found to be of mucinous type, 19 cases were found to be in grade I, 74 in grade II and seven cases were in grade III. Breast cancer has been classified into four major groups based on IHC profile ER/PR and HER2/neu expression. The groups were: Triple positive, ER/PR+, HER2-, ER/PR-, HER2/neu+ and triple negative) cases. Among 100 cases of breast cancer, 9 were of triple positive type, (ER/PR +, HER2/neu+), 28 cases were of ER/PR +, HER2- type, 19 were ER/PR-, HER2/neu +ve and 44 cases were of triple negative type (ER/PR-, HER2/neu-ve). 13 cases were of score 1 MMP-1out of which 7 (25.0%) were ER/PR+, HER2-, 1 (5.3%) case was ER/PR-, HER2/neu +ve and 5 (11.4%) cases were triple negative. Among 30 cases of MMP-1 score 4, 5(55.6%) cases were of triple positive type, 3 (10.7%) cases were of ER/PR +, HER 2/neu-ve type, 12(63.2%) cases were of ER/PR-, HER 2/neu+ve type, and 10 (22.7%) cases were of triple negative type. A significant p-value of <0.05 was obtained.

CONCLUSIONS: Among four IHC based subtypes, most frequent were triple negative breast cancers which showed high IHC score of MMP-I which is reported to be an important marker for metastatic potential in breast carcinoma.}, } @article {pmid35456414, year = {2022}, author = {Zadrożna-Nowak, A and Romanowicz, H and Zadrożny, M and Bryś, M and Forma, E and Smolarz, B}, title = {Analysis of Long Non-Coding RNA (lncRNA) uc.38 and uc.63 Expression in Breast Carcinoma Patients.}, journal = {Genes}, volume = {13}, number = {4}, pages = {}, pmid = {35456414}, issn = {2073-4425}, mesh = {*Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {Background. The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer. Aim. The presented work assessed the expression of two transcribed-ultra conserved regions−uc.63 and uc.38−in breast cancer tissue samples. Material and methods. The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group). Results. As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient’s age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035). Conclusion. The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.}, } @article {pmid35454045, year = {2022}, author = {Chen, K and Yin, G and Xu, W}, title = {Predictive Value of [18]F-FDG PET/CT-Based Radiomics Model for Occult Axillary Lymph Node Metastasis in Clinically Node-Negative Breast Cancer.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {35454045}, issn = {2075-4418}, abstract = {To develop and validate a radiomics model based on [18]F-FDG PET/CT images to preoperatively predict occult axillary lymph node (ALN) metastases in patients with invasive ductal breast cancer (IDC) with clinically node-negative (cN0); Methods: A total of 180 patients (mean age, 55 years; range, 31-82 years) with pathologically proven IDC and a preoperative [18]F-FDG PET/CT scan from January 2013 to January 2021 were included in this retrospective study. According to the intraoperative pathological results of ALN, we divided patients into the true-negative group and ALN occult metastasis group. Radiomics features were extracted from PET/CT images using Pyradiomics implemented in Python, t-tests, and LASSO were used to screen the feature, and the random forest (RF), support vector machine (SVM), stochastic gradient descent (SGD), and k-nearest neighbor (KNN) were used to build the prediction models. The best-performing model was further tested by the permutation test; Results: Among the four models, RF had the best prediction results, the AUC range of RF was 0.661-0.929 (mean AUC, 0.817), and the accuracy range was 65.3-93.9% (mean accuracy, 81.2%). The p-values of the permutation tests for the RF model with maximum and minimum accuracy were less than 0.01; Conclusions: The developed RF model was able to predict occult ALN metastases in IDC patients based on preoperative [18]F-FDG PET/CT radiomic features.}, } @article {pmid35453053, year = {2022}, author = {Aitken, GL and Correa, G and Samuels, S and Gannon, CJ and Llaguna, OH}, title = {Assessment of Textbook Oncologic Outcomes Following Modified Radical Mastectomy for Breast Cancer.}, journal = {The Journal of surgical research}, volume = {277}, number = {}, pages = {17-26}, doi = {10.1016/j.jss.2022.03.018}, pmid = {35453053}, issn = {1095-8673}, mesh = {*Breast Neoplasms/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy/adverse effects ; *Mastectomy, Modified Radical ; Retrospective Studies ; }, abstract = {INTRODUCTION: Textbook oncologic outcome (TOO) is a composite outcome measure attained when all desired short-term quality metrics are met following an oncologic operation. The objective of this study was to determine the incidence of TOO and its impact on the overall survival (OS) among patients with invasive ductal carcinoma (IDC) following modified radical mastectomy (MRM).

METHODS: The 2004-2017 National Cancer Database was queried for patients with non-metastatic IDC who underwent MRM. TOO was defined as having attained five metrics: resection with negative microscopic margins, American Joint Committee on Cancer compliant lymph node evaluation (n ≥ 10), no prolonged length of stay (50[th] percentile by year), no 30-d readmission, and no 30-d mortality. OS was defined as the time in months between the date of diagnosis and the date of death or last contact.

RESULTS: A total of 75,063 patients were identified, of which 40.8% achieved TOO. The TOO patients had a lower median age and were more likely to be White, privately insured, and without comorbidities. In terms of facility characteristics, patients with TOO were more likely to be seen in comprehensive community cancer programs with a high case-volume per year. The TOO group had a statistically significant higher median OS compared to the non-TOO group (165.6 versus 142.2 mo; P < 0.001). On multivariate analysis TOO was independently associated with a reduced risk of death (HR = 0.82; P < 0.001).

CONCLUSIONS: TOO is achieved in approximately 41% of patients undergoing MRM for IDC. Achieving TOO is associated with improved median OS and reduced risk of death. TOO therefore merits further attention in efforts to improve surgical outcomes.}, } @article {pmid35452911, year = {2022}, author = {Effiong, K and Hu, J and Xu, C and Zhang, Y and Yu, S and Tang, T and Huang, Y and Lu, Y and Li, W and Zeng, J and Xiao, X}, title = {3-Indoleacrylic acid from canola straw as a promising antialgal agent - Inhibition effect and mechanism on bloom-forming Prorocentrum donghaiense.}, journal = {Marine pollution bulletin}, volume = {178}, number = {}, pages = {113657}, doi = {10.1016/j.marpolbul.2022.113657}, pmid = {35452911}, issn = {1879-3363}, mesh = {*Dinoflagellida ; Harmful Algal Bloom ; Indoles ; Photosynthesis ; }, abstract = {Harmful algal blooms (HABs) have induced severe damage worldwide. A novel high-efficient antialgal natural chemical, 3-indoleacrylic acid (3-IDC) with a 5-day half-maximal inhibitory concentration (IC50, 5d), was discovered from canola straw, and its algal inhibition mechanism was investigated. Adverse effects were observed on the growth of P. donghaiense with 3-IDC addition, following an increase in reactive oxygen species (ROS) production. 3-IDC also hindered the photosynthetic mechanism of P. donghaiense cells. Transcriptional results showed 3-IDC inhibiting the functions of all the nutrient assimilating genes, down-regulated ribulose-1,5-bisphosphate carboxylase/oxygenase II, and cytochrome f genes. The expression of heat shock protein (HSP) 70 and 90 and rhodopsin genes were also suppressed. The binding affinity of investigated receptors was observed. The conformational changes induced by the spatial microstructural alteration through 3-IDC may further contribute to the perturbation of those enzyme catalytic activities. The present results provide new insights on controlling HABs using 3-IDC.}, } @article {pmid35447386, year = {2022}, author = {Pisano, CE and Kharouta, MZ and Harris, EE and Shenk, R and Lyons, JA}, title = {Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer.}, journal = {Practical radiation oncology}, volume = {12}, number = {6}, pages = {e493-e500}, doi = {10.1016/j.prro.2022.04.002}, pmid = {35447386}, issn = {1879-8519}, mesh = {Humans ; Female ; *Breast Neoplasms/radiotherapy/surgery/pathology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; *Re-Irradiation ; Prospective Studies ; Mastectomy, Segmental/methods ; *Brachytherapy/methods ; Treatment Outcome ; }, abstract = {PURPOSE: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation.

METHODS AND MATERIALS: This was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period.

RESULTS: From 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience.

CONCLUSIONS: APBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.}, } @article {pmid35444128, year = {2022}, author = {Ogikubo, M and Yoshida, T and Suganuma, N and Takahashi, A and Rino, Y and Masuda, M}, title = {[A Case of Pregnancy-Associated Breast Cancer Which Underwent Surgical Treatment during Pregnancy and Chemotherapy after Delivery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {49}, number = {4}, pages = {433-435}, pmid = {35444128}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/pathology/surgery ; Cesarean Section ; Chemotherapy, Adjuvant ; Female ; Humans ; Pregnancy ; *Pregnancy Complications, Neoplastic/drug therapy/pathology ; Receptor, ErbB-2 ; Sentinel Lymph Node Biopsy ; Trastuzumab ; }, abstract = {CASE: A 37-year-old pregnant woman arrived at our hospital with an abnormal mammogram.

MEDICAL HISTORY: Mammography performed in June 2018 revealed an abnormal shadow on the left breast. Cytology from the 6-mm tumor in the left upper-outer quadrant revealed a malignancy. At the same time, a transvaginal echo revealed cysts, and the patient was diagnosed at 5 weeks gestation. Needle biopsy revealed a luminal A-like cStage Ⅰ, cT1bN0M0 invasive ductal carcinoma (IDC). Tumor resection and sentinel lymph node biopsy were performed under local anesthesia at 12 weeks gestation, and post-delivery adjuvant therapy was planned. Histologic examination of the resected tumor revealed that it was HER2-positive(immunohistochemistry score 3+); therefore, we had to reconsider the use of trastuzumab and decided to administer it to the patient after childbirth. The patient gave birth by cesarean section, and weekly paclitaxel plus trastuzumab was initiated 7 months after surgery. The patient is currently alive without recurrence.

DISCUSSION: We faced several difficulties during the treatment of this patient. Postoperative adjuvant therapy is recommended to be administered 8 weeks after the surgical resection of the tumor. However, in our case, given that the tumor was HER2-positive, we could administer adjuvant therapy with trastuzumab only after delivery. Although the prevalence of breast cancer in women below the age of 40 years in Japan is currently as low as 4-6%, the incidence of pregnancy-associated breast cancer is predicted to increase as the number of elderly primigravida increases due to later marriage.}, } @article {pmid35439160, year = {2023}, author = {Guan, Y and Ren, Y and Sun, Q and Li, SE and Ma, H and Duan, J and Dai, Y and Cheng, B}, title = {Integrated Decision and Control: Toward Interpretable and Computationally Efficient Driving Intelligence.}, journal = {IEEE transactions on cybernetics}, volume = {53}, number = {2}, pages = {859-873}, doi = {10.1109/TCYB.2022.3163816}, pmid = {35439160}, issn = {2168-2275}, abstract = {Decision and control are core functionalities of high-level automated vehicles. Current mainstream methods, such as functional decomposition and end-to-end reinforcement learning (RL), suffer high time complexity or poor interpretability and adaptability on real-world autonomous driving tasks. In this article, we present an interpretable and computationally efficient framework called integrated decision and control (IDC) for automated vehicles, which decomposes the driving task into static path planning and dynamic optimal tracking that are structured hierarchically. First, the static path planning generates several candidate paths only considering static traffic elements. Then, the dynamic optimal tracking is designed to track the optimal path while considering the dynamic obstacles. To that end, we formulate a constrained optimal control problem (OCP) for each candidate path, optimize them separately, and follow the one with the best tracking performance. To unload the heavy online computation, we propose a model-based RL algorithm that can be served as an approximate-constrained OCP solver. Specifically, the OCPs for all paths are considered together to construct a single complete RL problem and then solved offline in the form of value and policy networks for real-time online path selecting and tracking, respectively. We verify our framework in both simulations and the real world. Results show that compared with baseline methods, IDC has an order of magnitude higher online computing efficiency, as well as better driving performance, including traffic efficiency and safety. In addition, it yields great interpretability and adaptability among different driving scenarios and tasks.}, } @article {pmid35435571, year = {2022}, author = {Tsuda, H and Kurosumi, M and Akiyama, F and Ohno, S and Saji, S and Masuda, N and Shimomura, A and Sato, N and Takao, S and Ohsumi, S and Tokuda, Y and Inaji, H and Watanabe, T}, title = {Validation of a nuclear grading system for resected stage I-IIIA, high-risk, node-negative invasive breast carcinoma in the N·SAS-BC 01 trial.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {29}, number = {4}, pages = {720-729}, pmid = {35435571}, issn = {1880-4233}, mesh = {*Breast Neoplasms/drug therapy/surgery ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; *Carcinoma, Lobular/drug therapy/surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Retrospective Studies ; }, abstract = {BACKGROUND: This retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20-30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients.

METHODS: Of 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated.

RESULTS: Local diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC.

CONCLUSIONS: The N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial.

TRIAL REGISTRATION NUMBER: UMIN000022571. Date of registration: June 1, 2016.}, } @article {pmid35425619, year = {2022}, author = {Park, DJ and Park, S and Ma, SW and Seo, H and Lee, SG and Lee, KE}, title = {Assessment of risks for breast cancer in a flight attendant exposed to night shift work and cosmic ionizing radiation: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {34}, number = {}, pages = {e5}, pmid = {35425619}, issn = {2052-4374}, abstract = {BACKGROUND: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data.

CASE PRESENTATION: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer.

CONCLUSIONS: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.}, } @article {pmid35419208, year = {2022}, author = {Al-Keilani, MS and Elstaty, R and Alqudah, MA}, title = {The Prognostic Potential of Neurokinin 1 Receptor in Breast Cancer and Its Relationship with Ki-67 Index.}, journal = {International journal of breast cancer}, volume = {2022}, number = {}, pages = {4987912}, pmid = {35419208}, issn = {2090-3170}, abstract = {BACKGROUND: Neurokinin 1 receptor (NK1R) is a promising biomarker and therapeutic target in breast cancer. This study was aimed at investigating the expression level of NK1R in breast cancer tissues and its relationship with proliferation index as measured by Ki-67, clinicopathological characteristics of patients, and overall survival rate.

METHODS: Immunohistochemical expression of NK1R and Ki-67 was measured in 164 paraffin-embedded breast cancer tissues of four molecular subtypes (42 HER2-enriched, 40 luminal A, 42 luminal B, and 40 triple negative). NK1R was scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff values for NK1R and Ki-67 were assessed by Cutoff Finder. Pearson's Chi-square (χ [2]) and Fisher's exact tests were used to compare the staining scores between groups. The Kaplan-Meier method with log-rank test was used for survival analysis. ANOVA and Student's t-test were used to compare group means.

RESULTS: A total of 164 patients were included in the study which represented females with invasive ductal carcinoma. NK1R was expressed at high levels in about 34% of investigated cases. The mean Ki-67 level was about 27% and 41.5% of sample had high Ki-67 (expression level > 22%). NK1R expression levels were associated with higher tumor grade (p = 0.021) and high Ki-67 (p = 0.012). NK1R expression negatively impacted overall survival in grade II tumors (p = 0.027).

CONCLUSION: NK1R contributes to cellular proliferation and is associated with negative prognosis in breast cancer. These findings suggest the potential role of NK1R as a therapeutic target in breast cancer.}, } @article {pmid35410836, year = {2022}, author = {Zhao, H and Ming, X and Yang, Z}, title = {DCIS (Ductal carcinoma in situ)-like invasive ductal carcinoma of the breast.}, journal = {Asian journal of surgery}, volume = {45}, number = {10}, pages = {1855-1856}, doi = {10.1016/j.asjsur.2022.03.113}, pmid = {35410836}, issn = {0219-3108}, mesh = {Breast/pathology ; *Breast Neoplasms/diagnostic imaging/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Female ; Humans ; Neoplasm Invasiveness/pathology ; }, } @article {pmid35410038, year = {2022}, author = {Abu-Kaf, S and Nakash, O and Hayat, T and Cohen, M}, title = {Social Support and Psychological Distress among the Bedouin Arab Elderly in Israel: The Moderating Role of Gender.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35410038}, issn = {1660-4601}, mesh = {Aged ; *Arabs/psychology ; Cross-Sectional Studies ; Female ; Humans ; Israel/epidemiology ; Male ; *Psychological Distress ; Social Support ; Stress, Psychological/epidemiology ; Surveys and Questionnaires ; }, abstract = {In Israel, as in other developed countries, mental health problems are common among older adults who are members of disadvantaged ethnic minorities that are experiencing cultural and social changes. The main goals of the current study were: (a) to examine gender differences in the levels of psychological distress and social support among Bedouin elders, and (b) to examine the moderating role of gender in the associations between social support indices and psychological distress. We used a cross-sectional design, and independent t-tests and hierarchical linear regression analysis were performed. The study was conducted in homes and in social clubs and community centers for elderly people and involved face-to-face interviews and self-administered questionnaires. A convenience sample of 170 Bedouin Arab elderly people living in Israel participated in the study. Participants completed self-report questionnaires that assessed psychological distress, perceived social support, instrumental social support, and socio-demographic characteristics. Male elders reported lower levels of psychological distress and higher levels of instrumental support. Female elders, who reported low levels of both perceived and instrumental support, also reported higher levels of psychological distress. Among the women, there were significant associations between psychological distress and perceived social support, and instrumental support only when the levels of support were low. This study underscores the moderating role of gender in the associations between different types of social support and psychological distress among elderly people belonging to ethnic and cultural underprivileged minority groups.}, } @article {pmid35410036, year = {2022}, author = {Shenkman, G and Segal-Engelchin, D and Taubman-Ben-Ari, O}, title = {What We Know and What Remains to Be Explored about LGBTQ Parent Families in Israel: A Sociocultural Perspective.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35410036}, issn = {1660-4601}, mesh = {Child ; Female ; Gender Identity ; *Homosexuality, Female/psychology ; Humans ; Israel ; Male ; Sexual Behavior ; *Sexual and Gender Minorities ; }, abstract = {This paper reviews research on gay and lesbian parent families in Israel through cultural lenses while recognizing the diversity of these families. The major aims of the review are: (1) to provide an overview of the situation of LGBTQ parent families in Israel, as well as of the sociocultural background of the Israeli context and its effects on sexual minorities and LGBTQ parent families; and (2) to identify the limitations and lacunas in the existing research and shed light on what remains to be explored. We searched numerous databases for relevant studies, adopting a narrative approach to summarize the main findings while taking into account the literature on the socio-cultural context in Israel and its impact on sexual minorities and LGBTQ parent families. The search yielded empirical results only for gay and lesbian parent families, with studies emphasizing the challenges they face and the factors related to their well-being and that of LGB individuals aspiring to become parents. In addition, it revealed that research on children's psychosocial adjustment as a function of parental sexual orientation is quite scarce in Israel. Moreover, it indicated the absence of investigations of bisexual, transgender, or queer parents. We conclude that the sociocultural context of Israel, including its pronatalist and familistic orientation, may play an important role in shaping the experiences of LGBTQ parent families, and should be taken into consideration when studying LGBTQ parents.}, } @article {pmid35406430, year = {2022}, author = {Cabarcas-Petroski, S and Schramm, L}, title = {BDP1 Alterations Correlate with Clinical Outcomes in Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {7}, pages = {}, pmid = {35406430}, issn = {2072-6694}, abstract = {TFIIIB is deregulated in a variety of cancers. However, few studies investigate the TFIIIB subunit BDP1 in cancer. BDP1 has not been studied in breast cancer patients. Herein, we analyzed clinical breast cancer datasets to determine if BDP1 alterations correlate with clinical outcomes. BDP1 copy number (n = 1602; p = 8.03 × 10[-9]) and mRNA expression (n = 130; p = 0.002) are specifically decreased in patients with invasive ductal carcinoma (IDC). In IDC, BDP1 copy number negatively correlates with high grade (n = 1992; p = 2.62 × 10[-19]) and advanced stage (n = 1992; p = 0.005). BDP1 mRNA expression also negatively correlated with high grade (n = 55; p = 6.81 × 10[-4]) and advanced stage (n = 593; p = 4.66 × 10[-4]) IDC. Decreased BDP1 expression correlated with poor clinical outcomes (n = 295 samples): a metastatic event at three years (p = 7.79 × 10[-7]) and cancer reoccurrence at three years (p = 4.81 × 10[-7]) in IDC. Decreased BDP1 mRNA correlates with patient death at three (p = 9.90 × 10[-6]) and five (p = 1.02 × 10[-6]) years. Both BDP1 copy number (n = 3785; p = 1.0 × 10[-14]) and mRNA expression (n = 2434; p = 5.23 × 10[-6]) are altered in triple-negative invasive breast cancer (TNBC). Together, these data suggest a role for BDP1 as potential biomarker in breast cancer and additional studies are warranted.}, } @article {pmid35405500, year = {2022}, author = {Acevedo, DS and Fang, WB and Rao, V and Penmetcha, V and Leyva, H and Acosta, G and Cote, P and Brodine, R and Swerdlow, R and Tan, L and Lorenzi, PL and Cheng, N}, title = {Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.}, journal = {Neoplasia (New York, N.Y.)}, volume = {28}, number = {}, pages = {100791}, pmid = {35405500}, issn = {1476-5586}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Ductal, Breast/metabolism/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cell Line, Tumor ; *Chemokine CCL2/genetics/metabolism ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local/metabolism/pathology ; *Proto-Oncogene Proteins c-met/metabolism ; *Receptors, CCR2/metabolism ; }, abstract = {With over 60,000 cases diagnosed annually in the US, ductal carcinoma in situ (DCIS) is the most prevalent form of early-stage breast cancer. Because many DCIS cases never progress to invasive ductal carcinomas (IDC), overtreatment remains a significant problem. Up to 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat DCIS for a subset of patients. By understanding the mechanisms of DCIS progression, we can develop new treatment strategies better tailored to patients. The chemokine CCL2 and its receptor CCR2 are known to regulate macrophage recruitment during inflammation and cancer progression. Recent studies indicate that increased CCL2/CCR2 signaling in breast epithelial cells enhance formation of IDC. Here, we characterized the molecular mechanisms important for CCL2/CCR2-mediated DCIS progression. Phospho-protein array profiling revealed that CCL2 stimulated phosphorylation of MET receptor tyrosine kinases in breast cancer cells. Co-immunoprecipitation and proximity ligation assays demonstrated that CCL2-induced MET activity depended on interactions with CCR2 and SRC. Extracellular flux analysis and biochemical assays revealed that CCL2/CCR2 signaling in breast cancer cells enhanced glycolytic enzyme expression and activity. CRISPR knockout and pharmacologic inhibition of MET revealed that CCL2/CCR2-induced breast cancer cell proliferation, survival, migration and glycolysis through MET-dependent mechanisms. In animals, MET inhibitors blocked CCR2-mediated DCIS progression and metabolism. CCR2 and MET were significantly co-expressed in patient DCIS and IDC tissues. In summary, MET receptor activity is an important mechanism for CCL2/CCR2-mediated progression and metabolism of early-stage breast cancer, with important clinical implications.}, } @article {pmid35402478, year = {2022}, author = {Feng, Y and Zhang, Y and Xiang, Y and Guo, K and Jin, H and Ruan, S and Guan, Z}, title = {Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Breast Invasive Ductal Carcinoma Patients After Surgery: A Large Population-Based Study.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {779220}, pmid = {35402478}, issn = {2296-875X}, abstract = {BACKGROUND: Breast cancer (BC) has become the most common malignancy worldwide, accounting for 11.7% of newly diagnosed cancer cases last year. Invasive ductal carcinoma (IDC) is the most common pathological type of BC. However, there were few studies to predict distant metastatic sites and overall survival (OS) of IDC patients.

METHODS: Post-operative IDC patients from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Nomograms were developed to predict the specific distant metastatic sites and OS of IDC patients. The performance of nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of IDC patients with distant metastases.

RESULTS: A total of 171,967 post-operative IDC patients were enrolled in our study. Univariate and multivariate analyses were used to establish the nomograms of significant variables. The AUC of the nomograms for the prediction of liver, lung, bone, and brain metastases was 0.903, 0.877, 0.863, and 0.811, respectively. In addition, the AUC of the nomogram for the prediction of 1-, 3-, and 5-year OS was 0.809, 0.813, 0.787, respectively. Calibration curves and DCA showed good consistency and clinical benefits, respectively.

CONCLUSIONS: We constructed new predictive models for liver, lung, brain, bone metastases and 1-, 3-, and 5-year OS in IDC patients. These can help clinicians to individualize the treatment of IDC patients, so that patients can get the more appropriate treatment options.}, } @article {pmid35402236, year = {2022}, author = {Li, YZ and Chen, B and Lin, XY and Zhang, GC and Lai, JG and Li, C and Lin, JL and Guo, LP and Xiao, WK and Mok, H and Ren, CY and Wen, LZ and Cao, FR and Lin, X and Qi, XF and Liu, Y and Liao, N}, title = {Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {830124}, pmid = {35402236}, issn = {2234-943X}, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population.

METHODS: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies.

RESULTS: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035).

CONCLUSIONS: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.}, } @article {pmid35397740, year = {2022}, author = {Ensenyat-Mendez, M and Rünger, D and Orozco, JIJ and Le, J and Baker, JL and Weidhaas, J and Marzese, DM and DiNome, ML}, title = {Epigenetic Signatures Predict Pathologic Nodal Stage in Breast Cancer Patients with Estrogen Receptor-Positive, Clinically Node-Positive Disease.}, journal = {Annals of surgical oncology}, volume = {29}, number = {8}, pages = {4716-4724}, pmid = {35397740}, issn = {1534-4681}, support = {CP17/00188//European Regional Development Fund/ ; PI19/01514)//European Regional Development Fund/ ; UL1TR000124UCLA//CTSI UCLA/ ; }, mesh = {Axilla/pathology ; *Breast Neoplasms/genetics/metabolism/surgery ; Epigenesis, Genetic ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node Biopsy/methods ; }, abstract = {BACKGROUND: Breast cancer patients with clinically positive nodes who undergo upfront surgery are often recommended for axillary lymph node dissection (ALND), yet more than half are found to have limited nodal disease (≤ 3 positive nodes, pN1) at surgery. In this study, we examined the efficiency of molecular classifiers in stratifying patients with clinically positive nodes to pN1 versus > pN1 disease.

METHODS: We evaluated the clinical and epigenetic data of patients in The Cancer Genome Atlas with estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma who underwent ALND for node-positive disease. Patients were divided into control (pN1, ≤ 3 positive nodes) and case (> pN1, > 3 positive nodes) groups. Machine learning algorithms were trained on 50% of the cohort and validated on the remaining 50% to identify DNA methylation signatures that predict > pN1 disease. Clinical variables and epigenetic signatures were compared.

RESULTS: Controls (n = 34) and case (n = 24) cohorts showed similar mean age (56.4 ± 12.2 vs. 57.6 ± 16.7 years; p = 0.77), number of nodes removed (16.1 ± 7.3 vs. 17.5 ± 6.2; p = 0.45), tumor grade (p = 0.76), presence of lymphovascular invasion (p = 0.18), extranodal extension (p = 0.17), tumor laterality (p = 0.89), and tumor location (p = 0.42). The mean number of positive nodes was significantly different (1.76 ± 0.82, pN1; 8.83 ± 5.36, > pN1; p < 0.001). Three epigenetic signatures (EpiSig14, EpiSig13, EpiSig10) based on DNA methylation patterns of the primary tumors demonstrated high accuracy in predicting > pN1 disease (area under the curve 0.98).

CONCLUSIONS: Epigenetic signatures have an excellent diagnostic accuracy for stratifying nodal disease in patients with clinically positive nodes. Validation of this tool is warranted and may provide an accurate and cost-effective method of identifying patients with predicted low nodal burden who could be spared the morbidity of ALND.}, } @article {pmid35393463, year = {2022}, author = {Foroozani, E and Akbari, A and Amanat, S and Rashidi, N and Bastam, D and Ataee, S and Sharifnia, G and Faraouei, M and Dianatinasab, M and Safdari, H}, title = {Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {5859}, pmid = {35393463}, issn = {2045-2322}, mesh = {*Breast Neoplasms/complications/etiology ; *Carcinoma, Ductal, Breast/complications/etiology ; *Carcinoma, Lobular/epidemiology/etiology/pathology ; Case-Control Studies ; Diet, Western ; Female ; Humans ; }, abstract = {Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.}, } @article {pmid35392241, year = {2022}, author = {Jiang, Y and Chai, L and Dong, D and Chughtai, AR and Kong, W}, title = {Case Report: Mucocele-Like Tumor of the Breast Associated With Ductal Carcinoma In Situ.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {855028}, pmid = {35392241}, issn = {2234-943X}, abstract = {Mucocele-like tumor of the breast is histologically characterized as mucin-containing cysts with mucin leaking to the stroma. It could be associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We report a case of mucocele-like tumor of the breast associated with DCIS confirmed by paraffin section. We review the literature and discuss the imaging features, pathology, and clinical management of the lesion. These lesions demonstrate characteristic imaging features, and we especially highlight the MR characteristics, as they have not been well documented. Performing a diagnostic fine-needle aspiration cytology (FNAC) of mucocele-like tumor carries a risk of tumor underestimation; therefore, excision for all mucocele-like tumors is suggested to be the best approach. However, some recent reports recommend close follow-up for patients with low-risk factors who have mucocele-like tumor without atypia on FNAC.}, } @article {pmid35389579, year = {2022}, author = {Clarey, D and DiMaio, D and Trowbridge, R}, title = {Deep Sweet Syndrome Secondary to Pegfilgrastim.}, journal = {Journal of drugs in dermatology : JDD}, volume = {21}, number = {4}, pages = {422-424}, doi = {10.36849/JDD.4794}, pmid = {35389579}, issn = {1545-9616}, mesh = {Filgrastim/adverse effects ; Granulocyte Colony-Stimulating Factor/adverse effects ; Humans ; Polyethylene Glycols/adverse effects ; *Sweet Syndrome/chemically induced/diagnosis/drug therapy ; }, abstract = {Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.}, } @article {pmid35388016, year = {2022}, author = {Van Bavel, JJ and Cichocka, A and Capraro, V and Sjåstad, H and Nezlek, JB and Pavlović, T and Alfano, M and Gelfand, MJ and Azevedo, F and Birtel, MD and Cislak, A and Lockwood, PL and Ross, RM and Abts, K and Agadullina, E and Aruta, JJB and Besharati, SN and Bor, A and Choma, BL and Crabtree, CD and Cunningham, WA and De, K and Ejaz, W and Elbaek, CT and Findor, A and Flichtentrei, D and Franc, R and Gjoneska, B and Gruber, J and Gualda, E and Horiuchi, Y and Huynh, TLD and Ibanez, A and Imran, MA and Israelashvili, J and Jasko, K and Kantorowicz, J and Kantorowicz-Reznichenko, E and Krouwel, A and Laakasuo, M and Lamm, C and Leygue, C and Lin, MJ and Mansoor, MS and Marie, A and Mayiwar, L and Mazepus, H and McHugh, C and Minda, JP and Mitkidis, P and Olsson, A and Otterbring, T and Packer, DJ and Perry, A and Petersen, MB and Puthillam, A and Riaño-Moreno, JC and Rothmund, T and Santamaría-García, H and Schmid, PC and Stoyanov, D and Tewari, S and Todosijević, B and Tsakiris, M and Tung, HH and Umbreș, RG and Vanags, E and Vlasceanu, M and Vonasch, A and Yucel, M and Zhang, Y and Abad, M and Adler, E and Akrawi, N and Mdarhri, HA and Amara, H and Amodio, DM and Antazo, BG and Apps, M and Ay, FC and Ba, MH and Barbosa, S and Bastian, B and Berg, A and Bernal-Zárate, MP and Bernstein, M and Białek, M and Bilancini, E and Bogatyreva, N and Boncinelli, L and Booth, JE and Borau, S and Buchel, O and Cameron, CD and Carvalho, CF and Celadin, T and Cerami, C and Chalise, HN and Cheng, X and Cian, L and Cockcroft, K and Conway, J and Córdoba-Delgado, MA and Crespi, C and Crouzevialle, M and Cutler, J and Cypryańska, M and Dabrowska, J and Daniels, MA and Davis, VH and Dayley, PN and Delouvee, S and Denkovski, O and Dezecache, G and Dhaliwal, NA and Diato, AB and Di Paolo, R and Drosinou, M and Dulleck, U and Ekmanis, J and Ertan, AS and Etienne, TW and Farhana, HH and Farkhari, F and Farmer, H and Fenwick, A and Fidanovski, K and Flew, T and Fraser, S and Frempong, RB and Fugelsang, JA and Gale, J and Garcia-Navarro, EB and Garladinne, P and Ghajjou, O and Gkinopoulos, T and Gray, K and Griffin, SM and Gronfeldt, B and Gümren, M and Gurung, RL and Halperin, E and Harris, E and Herzon, V and Hruška, M and Huang, G and Hudecek, MFC and Isler, O and Jangard, S and Jørgensen, FJ and Kachanoff, F and Kahn, J and Dangol, AK and Keudel, O and Koppel, L and Koverola, M and Kubin, E and Kunnari, A and Kutiyski, Y and Laguna, O and Leota, J and Lermer, E and Levy, J and Levy, N and Li, C and Long, EU and Longoni, C and Maglić, M and McCashin, D and Metcalf, AL and Mikloušić, I and El Mimouni, S and Miura, A and Molina-Paredes, J and Monroy-Fonseca, C and Morales-Marente, E and Moreau, D and Muda, R and Myer, A and Nash, K and Nesh-Nash, T and Nitschke, JP and Nurse, MS and Ohtsubo, Y and Oldemburgo de Mello, V and O'Madagain, C and Onderco, M and Palacios-Galvez, MS and Palomäki, J and Pan, Y and Papp, Z and Pärnamets, P and Paruzel-Czachura, M and Pavlović, Z and Payán-Gómez, C and Perander, S and Pitman, MM and Prasad, R and Pyrkosz-Pacyna, J and Rathje, S and Raza, A and Rêgo, GG and Rhee, K and Robertson, CE and Rodríguez-Pascual, I and Saikkonen, T and Salvador-Ginez, O and Sampaio, WM and Santi, GC and Santiago-Tovar, N and Savage, D and Scheffer, JA and Schönegger, P and Schultner, DT and Schutte, EM and Scott, A and Sharma, M and Sharma, P and Skali, A and Stadelmann, D and Stafford, CA and Stanojević, D and Stefaniak, A and Sternisko, A and Stoica, A and Stoyanova, KK and Strickland, B and Sundvall, J and Thomas, JP and Tinghög, G and Torgler, B and Traast, IJ and Tucciarelli, R and Tyrala, M and Ungson, ND and Uysal, MS and Van Lange, PAM and van Prooijen, JW and van Rooy, D and Västfjäll, D and Verkoeijen, P and Vieira, JB and von Sikorski, C and Walker, AC and Watermeyer, J and Wetter, E and Whillans, A and Willardt, R and Wohl, MJA and Wójcik, AD and Wu, K and Yamada, Y and Yilmaz, O and Yogeeswaran, K and Ziemer, CT and Zwaan, RA and Boggio, PS}, title = {Author Correction: National identity predicts public health support during a global pandemic.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1949}, doi = {10.1038/s41467-022-29658-x}, pmid = {35388016}, issn = {2041-1723}, support = {I 3381/FWF_/Austrian Science Fund FWF/Austria ; }, } @article {pmid35386523, year = {2022}, author = {Leshem, R and Icht, M and Ben-David, BM}, title = {Processing of Spoken Emotions in Schizophrenia: Forensic and Non-forensic Patients Differ in Emotional Identification and Integration but Not in Selective Attention.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {847455}, pmid = {35386523}, issn = {1664-0640}, abstract = {Patients with schizophrenia (PwS) typically demonstrate deficits in visual processing of emotions. Less is known about auditory processing of spoken-emotions, as conveyed by the prosodic (tone) and semantics (words) channels. In a previous study, forensic PwS (who committed violent offenses) identified spoken-emotions and integrated the emotional information from both channels similarly to controls. However, their performance indicated larger failures of selective-attention, and lower discrimination between spoken-emotions, than controls. Given that forensic schizophrenia represents a special subgroup, the current study compared forensic and non-forensic PwS. Forty-five PwS listened to sentences conveying four basic emotions presented in semantic or prosodic channels, in different combinations. They were asked to rate how much they agreed that the sentences conveyed a predefined emotion, focusing on one channel or on the sentence as a whole. Their performance was compared to that of 21 forensic PwS (previous study). The two groups did not differ in selective-attention. However, better emotional identification and discrimination, as well as better channel integration were found for the forensic PwS. Results have several clinical implications: difficulties in spoken-emotions processing might not necessarily relate to schizophrenia; attentional deficits might not be a risk factor for aggression in schizophrenia; and forensic schizophrenia might have unique characteristics as related to spoken-emotions processing (motivation, stimulation).}, } @article {pmid35386144, year = {2022}, author = {Zeeshan, S and Siddiqiui, T and Shaukat, F and Tariq, MU and Khan, N and Vohra, L}, title = {Male Breast Cancer: The Three Decades' Experience of a Tertiary Care Hospital in a Lower-Middle Income Country.}, journal = {Cureus}, volume = {14}, number = {2}, pages = {e22670}, pmid = {35386144}, issn = {2168-8184}, abstract = {Introduction Male breast cancer is uncommon and managed on the guidelines of female breast cancer due to tumor rarity. We sought to identify the incidence, clinicopathological features, and survival of all male breast cancer patients managed in our hospital. Methods A retrospective cross-sectional study was conducted at Aga Khan University Hospital (AKUH), Karachi, Pakistan, from January 1986 to December 2018. Demographic data, treatment records, and follow-up data of all male breast cancer patients who were treated at AKUH was reviewed. Results Thirty-eight out of 42 patients who presented over a period of 32 years were included. The mean age was 63 years. The most common tumor type and subtype were invasive ductal carcinoma (89.5%) and luminal A (73.7%), respectively. The majority (36.8%) of the patients presented at stage III. Among 30 (78.9%) patients who underwent surgery, mastectomy was performed in 30 (78.9%), upfront axillary clearance in 24 (63.2%), axillary sampling in five (15.1%) cases, and sentinel lymph node biopsy in one (2.6%) case. Neoadjuvant chemotherapy was given to 10 (26.3%) patients, and adjuvant chemotherapy to eight (21.1%) patients. Adjuvant hormonal treatment was administered to 22 (57.9%) patients, and 13 (34%) patients received adjuvant radiation to the chest wall. The five-year overall survival was 38.2% and the median survival was 36 months. The five-year disease-free survival (DFS) was found to be 33.7%. Conclusion Breast cancer in males presents at an advanced stage with poor survival. Multicenter studies are required to accurately identify incidence, prognostic factors, and outcomes in order to have a better understanding of its management.}, } @article {pmid35384476, year = {2023}, author = {Tiiri, E and Uotila, J and Elonheimo, H and Sillanmäki, L and Brunstein Klomek, A and Sourander, A}, title = {Bullying at 8 years and violent offenses by 31 years: the Finnish nationwide 1981 birth cohort study.}, journal = {European child & adolescent psychiatry}, volume = {32}, number = {9}, pages = {1667-1678}, pmid = {35384476}, issn = {1435-165X}, support = {320162//Academy of Finland/ ; 303581//Academy of Finland/ ; 308552//Academy of Finland/ ; }, mesh = {Adult ; Child ; Humans ; Male ; Female ; Cohort Studies ; Finland/epidemiology ; Aggression ; *Bullying ; *Crime Victims ; }, abstract = {This study explored the associations between bullying perpetration and victimization at 8 years of age and violent offenses by the age of 31. Data were obtained for subjects enrolled in a population-based longitudinal birth cohort study. In 1989, 5813 8-year-old children (attrition 3.4%), and their parents and teachers, were surveyed about bullying. When 5405 subjects (attrition 10.2%) were 15-31 years of age, violent offenses were extracted from the Finnish National Police Register. We analyzed the data by sex and categorized bullying perpetration and victimization by frequency. Violent offenses were categorized by severity. Cox regression analyses estimated the hazard ratios (HRs) and 95% confidence intervals (95% CIs). When they were compared to males who had not been bullies at 8 years of age, frequent male bullies had an increased hazard for violent offenses (adjusted HR 3.01, 95% CI 2.11-4.33) and severe violent offenses (adjusted HR 2.86, 95% CI 1.07-7.59) as adults, even when the data were controlled for them being victims, parental education level, family structure and child psychopathology. Frequent female bullies also had an increased hazard for violent offenses, compared to those who had not bullied others (adjusted HR 5.27, 95% CI 1.51-18.40). Frequent male bullying was associated with higher odds for violent offenses compared to only bullying sometimes. Being a victim was not associated with violent offenses. Preventing childhood bullying could reduce violent offenses by both sexes.}, } @article {pmid35384456, year = {2022}, author = {Bhaludin, BN and Tunariu, N and Koh, DM and Messiou, C and Okines, AF and McGrath, SE and Ring, AE and Parton, MM and Sharma, B and Gagliardi, T and Allen, SD and Pope, R and Johnston, SRD and Downey, K}, title = {A review on the added value of whole-body MRI in metastatic lobular breast cancer.}, journal = {European radiology}, volume = {32}, number = {9}, pages = {6514-6525}, pmid = {35384456}, issn = {1432-1084}, mesh = {*Bone Neoplasms/secondary ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/methods ; Positron Emission Tomography Computed Tomography/methods ; Positron-Emission Tomography/methods ; Whole Body Imaging/methods ; }, abstract = {Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.}, } @article {pmid35384019, year = {2022}, author = {Rijstenberg, LL and Hansum, T and Kweldam, CF and Kümmerlin, IP and Remmers, S and Roobol, MJ and van Leenders, GJLH}, title = {Large and small cribriform architecture have similar adverse clinical outcome on prostate cancer biopsies.}, journal = {Histopathology}, volume = {80}, number = {7}, pages = {1041-1049}, pmid = {35384019}, issn = {1365-2559}, mesh = {*Adenocarcinoma/pathology ; Biopsy ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Male ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; *Prostatic Neoplasms/pathology ; }, abstract = {AIMS: Invasive cribriform and intraductal carcinoma (IDC) are associated with adverse outcome in prostate cancer patients, with the large cribriform pattern having the worst outcome in radical prostatectomies. Our objective was to determine the impact of the large and small cribriform patterns in prostate cancer biopsies.

METHODS AND RESULTS: Pathological revision was carried out on biopsies of 1887 patients from the European Randomised Study of Screening for Prostate Cancer. The large cribriform pattern was defined as having at least twice the size of adjacent benign glands. The median follow-up time was 13.4 years. Hazard ratios for metastasis-free survival (MFS) and disease-specific survival (DSS) were calculated using Cox proportional hazards regression. Any cribriform pattern was found in 280 of 1887 men: 1.1% IDC in grade group (GG) 1, 18.2% in GG2, 57.1% in GG3, 55.4% in GG4 and 59.3% in GG5; the large cribriform pattern was present in 0, 0.5, 9.8, 18.1 and 17.3%, respectively. In multivariable analyses, small and large cribriform patterns were both (P < 0.005) associated with worse MFS [small: hazard ratio (HR) = 3.04, 95% confidence interval (CI) = 1.93-4.78; large: HR = 3.17, 95% CI = 1.68-5.99] and DSS (small: HR = 4.07, 95% CI = 2.51-6.62; large: HR = 4.13, 95% CI = 2.14-7.98). Patients with the large cribriform pattern did not have worse MFS (P = 0.77) or DSS (P = 0.96) than those with the small cribriform pattern.

CONCLUSIONS: Both small and large cribriform patterns are associated with worse MFS and DSS in prostate cancer biopsies. Patients with the large cribriform pattern on biopsy have a similar adverse outcome as those with the small cribriform pattern.}, } @article {pmid35380021, year = {2022}, author = {Adin, ME and Wu, J and Isufi, E and Tsui, E and Pucar, D}, title = {Ipsilateral Malignant Axillary Lymphadenopathy and Contralateral Reactive Lymph Nodes in a COVID-19 Vaccine Recipient With Breast Cancer.}, journal = {Journal of breast cancer}, volume = {25}, number = {2}, pages = {140-144}, pmid = {35380021}, issn = {1738-6756}, abstract = {Vaccine-related axillary nodal enlargement is a common benign condition that many mRNA vaccine receivers experience. However, a false attribution of axillary swelling to vaccination may result in delay in cancer care and potential disease progression, particularly in breast cancer patients presenting with ipsilateral axillary lymphadenopathy. We report the case of a 41-year-old pre-menopausal female who presented with suspicious axillary nodal enlargement and a right breast lump (triple-negative invasive ductal carcinoma) after recent administration of the second dose of Moderna mRNA coronavirus disease 2019 (COVID-19) vaccine. On imaging, bilateral axillary lymph nodes were detected. The ipsilateral right-sided node was proven to be metastatic, whereas contralateral nodes were related to a recent mRNA COVID-19 vaccination. Right-sided lymph node had intense uptake (maximum standardized uptake value [SUVmax] = 5), while the contralateral reactive nodes were mildly avid (SUVmax = 2.6). On magnetic resonance imaging, the right-sided node revealed asymmetric cortical thickening and marked cortical enhancement as opposed to normal-appearing left-sided nodes.}, } @article {pmid35379029, year = {2022}, author = {Ben-David, BM and Keisari, S and Palgi, Y}, title = {Vaccine and Psychological Booster: Factors Associated With Older Adults' Compliance to the Booster COVID-19 Vaccine in Israel.}, journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society}, volume = {41}, number = {7}, pages = {1636-1640}, pmid = {35379029}, issn = {1552-4523}, mesh = {Aged ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines/therapeutic use ; Humans ; Israel ; Vaccination/psychology ; *Vaccines ; }, abstract = {Israel became the first country to offer the booster COVID-19 vaccination. The study tested for the first time the role of sense of control (SOC) due to vaccinations, trust and vaccination hesitancy (VH), and their association with compliance to the booster COVID-19 vaccine among older adults, during the first 2 weeks of the campaign. 400 Israeli citizens (≥ 6 years old), eligible for the booster vaccine, responded online. They completed demographics, self-reports, and booster vaccination status (already vaccinated, booked-a-slot, vaccination intent, and vaccination opposers). Multinomial logistic regression was conducted with pseudo R[2] = .498. Higher SOC and lower VH were related to the difference between early and delayed vaccination (booked-a-slot, OR = 0.7 [0.49-0.99]; 2.2 [1.32-3.62], intent OR = 0.6 [0.42-0.98]; 2.7 [1.52-4.86]), as well as to rejection (OR = 0.3 [0.11-0.89]; 8.5 [3.39-21.16]). Increased trust was only related to the difference between early vaccinations and vaccine rejection (OR = 0.3 [0.11-0.89]). We suggest that SOC, as well as low VH, can be used as positive motivators, encouraging earlier vaccinations in older age.}, } @article {pmid35378329, year = {2022}, author = {Wolff, G and Sakurai, M and Mhamane, A and Troullinaki, M and Maida, A and Deligiannis, IK and Yin, K and Weber, P and Morgenstern, J and Wieder, A and Kwon, Y and Sekar, R and Zeigerer, A and Roden, M and Blüher, M and Volk, N and Poth, T and Hackert, T and Wiedmann, L and De Angelis Rigotti, F and Rodriguez-Vita, J and Fischer, A and Mukthavaram, R and Limphong, P and Tachikawa, K and Karmali, P and Payne, J and Chivukula, P and Ekim-Üstünel, B and Martinez-Jimenez, CP and Szendrödi, J and Nawroth, P and Herzig, S}, title = {Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.}, journal = {Molecular metabolism}, volume = {60}, number = {}, pages = {101487}, pmid = {35378329}, issn = {2212-8778}, mesh = {Animals ; *Diabetes Mellitus, Type 2/metabolism ; Fibrosis ; Hepatocytes/metabolism ; Humans ; *Insulin Resistance ; Lipids ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; Transcription Factors/metabolism ; }, abstract = {OBJECTIVE: Fibrotic organ responses have recently been identified as long-term complications in diabetes. Indeed, insulin resistance and aberrant hepatic lipid accumulation represent driving features of progressive non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to fibrosis. Effective pharmacological regimens to stop progressive liver disease are still lacking to-date.

METHODS: Based on our previous discovery of transforming growth factor beta-like stimulated clone (TSC)22D4 as a key driver of insulin resistance and glucose intolerance in obesity and type 2 diabetes, we generated a TSC22D4-hepatocyte specific knockout line (TSC22D4-HepaKO) and exposed mice to control or NASH diet models. Mechanistic insights were generated by metabolic phenotyping and single-nuclei RNA sequencing.

RESULTS: Hepatic TSC22D4 expression was significantly correlated with markers of liver disease progression and fibrosis in both murine and human livers. Indeed, hepatic TSC22D4 levels were elevated in human NASH patients as well as in several murine NASH models. Specific genetic deletion of TSC22D4 in hepatocytes led to reduced liver lipid accumulation, improvements in steatosis and inflammation scores and decreased apoptosis in mice fed a lipogenic MCD diet. Single-nuclei RNA sequencing revealed a distinct TSC22D4-dependent gene signature identifying an upregulation of mitochondrial-related processes in hepatocytes upon loss of TSC22D4. An enrichment of genes involved in the TCA cycle, mitochondrial organization, and triglyceride metabolism underscored the hepatocyte-protective phenotype and overall decreased liver damage as seen in mouse models of hepatocyte-selective TSC22D4 loss-of-function.

CONCLUSIONS: Together, our data uncover a new connection between targeted depletion of TSC22D4 and intrinsic metabolic processes in progressive liver disease. Hepatocyte-specific reduction of TSC22D4 improves hepatic steatosis and promotes hepatocyte survival via mitochondrial-related mechanisms thus paving the way for targeted therapies.}, } @article {pmid35372457, year = {2022}, author = {Niknam, K and Safaei, A and Ghaderi, A}, title = {Evaluation of the Prognostic Value of CD56 (140 kDa Isoform) Expression in Breast Cancer Tissues: an Eight-Year Retrospective Study.}, journal = {Iranian biomedical journal}, volume = {26}, number = {3}, pages = {175-182}, pmid = {35372457}, issn = {2008-823X}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/pathology ; *CD56 Antigen/genetics ; Female ; Humans ; Mastectomy ; Prognosis ; Protein Isoforms/genetics ; Retrospective Studies ; }, abstract = {BACKGROUND: Identification of specific antigens is highly beneficial for early detection, diagnosis, staging, and outcome prediction of cancer. This study aimed to evaluate the expression and prognostic value of CD56 (140 kDa isoform) in invasive ductal carcinoma (IDC).

METHODS: Sixty-five patients with IDC who underwent radical surgery or mastectomy as the primary treatment were included. Proper formalin-fixed and paraffin embedded tissue blocks of the patients were prepared and stained by IHC for CD56 (140 kDa isoform) molecule. Chi-square and fisher exact tests were used to compare the results against the clinicopathologic data of patients. Kaplan-Meier and log-rank test were employed to study the prognostic value of the target antigen.

RESULTS: The expression pattern of CD56 was granular and cytoplasmic. There were significant associations between the intensity of CD56 expression in invasive cells and carcinoma in situ (p = 0.005) and normal ducts (p = 0.010). Among all clinicipathologic parameters, there was only a significant association between the expression of estrogen receptor (ER) and CD56 (p = 0.023). Neither OS (overall survival; p = 0.356) nor DFS (disease-free survival; p = 0.976) had significant correlation with CD56 expression.

CONCLUSION: Our data indicated that the CD56 marker offers no prognostic value in terms of predicting the OS or DFS for up to eight years after primary surgery. Furthermore, the intensity of its expression is similar between normal, non-invasive, and invasive cells. Considering the generally better outcome of ER+ BC patients than their ER-counterparts, the CD56 marker may be indirectly associated with a more favorable prognosis among IDC patients.}, } @article {pmid35369542, year = {2022}, author = {Sugiyama, H and Tsutsumi, S and Watanabe, A and Nonaka, S and Okura, H and Izumi, H and Ishii, H}, title = {A large cystic meningioma incidentally detected during general examination for breast cancer.}, journal = {Radiology case reports}, volume = {17}, number = {5}, pages = {1777-1783}, pmid = {35369542}, issn = {1930-0433}, abstract = {A 57-year-old woman who underwent needle biopsy for a subcutaneous mass in the breast was diagnosed with invasive ductal carcinoma. General examination incidentally revealed an intracranial tumor. At presentation, the patient showed memory disturbance but no focal neurological deficits. Cranial computed tomography (CT) revealed a large, hypodense cyst in the left frontotemporal region, involving a tumor with extensive hyperostotic changes in the left sphenoid and frontal bones. Magnetic resonance imaging showed that the tumor was attached to the dura mater of the pterional region and extensively enhanced, with involvement of the frontal and sphenoid bones. The less vascular tumor was removed en bloc by drilling the affected sphenoid and frontal bones as much as possible. The microscopic findings of the tumor were consistent with meningothelial meningioma with invasion into the dura mater and bone. Cystic meningioma should be considered when encountered with a dural-based cystic tumor, even in patients with cancer. In such circumstances, prompt and preferential resection may be indicated for intracranial tumors for timely initiation of the long-term treatment of cancer.}, } @article {pmid35368648, year = {2022}, author = {Thom, RL and Dalle-Ave, A and Bunnik, EM and Krones, T and Van Assche, K and Ruck Keene, A and Cronin, AJ}, title = {Inequitable Access to Transplants: Adults With Impaired Decision-Making Capacity.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {35}, number = {}, pages = {10084}, pmid = {35368648}, issn = {1432-2277}, support = {203376/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; *Healthcare Disparities ; Humans ; }, abstract = {Inequitable access to deceased donor organs for transplantation has received considerable scrutiny in recent years. Emerging evidence suggests patients with impaired decision-making capacity (IDC) face inequitable access to transplantation. The "Ethical and Legal Issues" working group of the European Society of Transplantation undertook an expert consensus process. Literature relating to transplantation in patients with IDC was examined and collated to investigate whether IDC is associated with inferior transplant outcomes and the legitimacy of this healthcare inequality was examined. Even though the available evidence of inferior transplant outcomes in these patients is limited, the working group concluded that access to transplantation in patients with IDC may be inequitable. Consequently, we argue that IDC should not in and of itself be considered as a barrier to either registration on the transplant waiting list or allocation of an organ. Strategies for non-discrimination should focus on ensuring eligibility is based upon sound evidence and outcomes without reference to non-medical criteria. Recommendations to support policy makers and healthcare providers to reduce unintended inequity and inadvertent discrimination are set out. We call upon transplant centres and national bodies to include data on decision-making capacity in routine reporting schedules in order to improve the evidence base upon which organ policy decisions are made going forward.}, } @article {pmid35364707, year = {2023}, author = {Wu, Y and Sun, S and Huang, Y and Xiao, M and Zhao, X and Lu, X and Xia, B and Qiao, K and Zhang, S and Wu, Q and Xiong, J and Cheng, S and Song, Y}, title = {Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {3}, pages = {1175-1184}, pmid = {35364707}, issn = {1432-1335}, support = {No.HLJ2019010//Ministry of Education Chunhui Project Cooperative Research Project/ ; No.LH2020H120//Heilongjiang Natural Science Foundation of China/ ; No.JJZD2020-04//Haiyan Research Fund of Harbin Medical University Cancer Hospital/ ; }, mesh = {Humans ; Female ; *Paget's Disease, Mammary/complications/metabolism/pathology ; Receptors, Androgen ; Prognosis ; Gene Expression ; *Breast Neoplasms/complications ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value.

METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC).

RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P = 0.037) and pathological N stage (P = 0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P = 0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P = 0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P = 0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P = 0.029).

CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.}, } @article {pmid35360132, year = {2022}, author = {Keisari, S and Palgi, Y and Ring, L and Folkman, A and Ben-David, BM}, title = {"Post-lockdown Depression": Adaptation Difficulties, Depressive Symptoms, and the Role of Positive Solitude When Returning to Routine After the Lifting of Nation-Wide COVID-19 Social Restrictions.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {838903}, pmid = {35360132}, issn = {1664-0640}, abstract = {OBJECTIVES: The aim of the current study was to identify difficulties in adapting to normal life once COVID-19 lockdown has been lifted. Israel was used as a case study, as COVID-19 social restrictions, including a nation-wide lockdown, were lifted almost completely by mid-April 2021, following a large-scale vaccination operation.

METHODS: A sample of 293 mid-age and older Israeli adults (M age = 61.6 ± 12.8, range 40-85 years old) reported on return-to-routine adaptation difficulties (on a novel index), depression, positive solitude, and several demographic factors.

RESULTS: Of the participants, 40.4% met the criteria of (at least) mild depressive symptoms. Higher levels of adaptation difficulties were related to higher ratios of clinical depressive symptoms. This link was moderated by positive solitude. Namely, the association between return-to-routine adaptation difficulties and depression was mainly indicated for individuals with low positive solitude.

CONCLUSIONS: The current findings are of special interest to public welfare, as adaptation difficulties were associated with higher chance for clinical depressive symptoms, while positive solitude was found to be as an efficient moderator during this period. The large proportion of depressive symptoms that persist despite lifting of social restrictions should be taken into consideration by policy makers when designing return-to-routine plans.}, } @article {pmid35356428, year = {2022}, author = {Ajaz, S and Zaidi, SE and Ali, S and Siddiqa, A and Memon, MA}, title = {Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {820610}, pmid = {35356428}, issn = {1664-8021}, abstract = {Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately and accurately in highly-consanguineous Pakistani population. In the present discovery case series, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy gender-matched controls. The clinico-pathological features were evaluated by descriptive analysis and Pearson χ[2] test (with significant p-value <0.05). The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the analyses were stratified on the basis of age (≤40 years vs. >40 years) and ethnicity. The breast cancer gene panel assay was carried out by BROCA, which is a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (≤40 years) was higher in Sindhis (n = 12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grade III (50%), tumor size 2-5 cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients, which was not significantly associated with younger age or any particular ethnicity. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of hereditary-based preventive and treatment strategies against breast cancers in Pakistani population.}, } @article {pmid35356272, year = {2022}, author = {He, Q and Fan, B and Du, P and Jin, Y}, title = {Construction and Validation of Two Hepatocellular Carcinoma-Progression Prognostic Scores Based on Gene Set Variation Analysis.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {806989}, pmid = {35356272}, issn = {2296-634X}, abstract = {Background: Liver hepatocellular carcinoma (LIHC) remains a global health challenge with a low early diagnosis rate and high mortality. Therefore, finding new biomarkers for diagnosis and prognosis is still one of the current research priorities. Methods: Based on the variation of gene expression patterns in different stages, the LIHC-development genes (LDGs) were identified by differential expression analysis. Then, prognosis-related LDGs were screened out to construct the LIHC-unfavorable gene set (LUGs) and LIHC-favorable gene set (LFGs). Gene set variation analysis (GSVA) was conducted to build prognostic scoring models based on the LUGs and LFGs. ROC curve analysis and univariate and multivariate Cox regression analysis were carried out to verify the diagnostic and prognostic utility of the two GSVA scores in two independent datasets. Additionally, the key LCGs were identified by the intersection analysis of the PPI network and univariate Cox regression and further evaluated their performance in expression level and prognosis prediction. Single-sample GSEA (ssGSEA) was performed to understand the correlation between the two GSVA enrichment scores and immune activity. Result: With the development of LIHC, 83 LDGs were gradually upregulated and 247 LDGs were gradually downregulated. Combining with LIHC survival analysis, 31 LUGs and 32 LFGs were identified and used to establish the LIHC-unfavorable GSVA score (LUG score) and LIHC-favorable GSVA score (LFG score). ROC curve analysis and univariate/multivariate Cox regression analysis suggested the LUG score and LFG score could be great indicators for the early diagnosis and prognosis prediction. Four genes (ESR1, EHHADH, CYP3A4, and ACADL) were considered as the key LCGs and closely related to good prognosis. The frequency of TP53 mutation and copy number variation (CNV) were high in some LCGs. Low-LFG score patients have active metabolic activity and a more robust immune response. The high-LFG score patients characterized immune activation with the higher infiltration abundance of type I T helper cells, DC, eosinophils, and neutrophils, while the high-LUG score patients characterized immunosuppression with the higher infiltration abundance of type II T helper cells, TRegs, and iDC. The high- and low-LFG score groups differed significantly in immunotherapy response scores, immune checkpoints expression, and IC50 values of common drugs. Conclusion: Overall, the LIHC-progression characteristic genes can be great diagnostic and prognostic signatures and the two GSVA score systems may become promising indices for guiding the tumor treatment of LIHC patients.}, } @article {pmid35349777, year = {2022}, author = {Oron, Y and Ben David, BM and Doron, G}, title = {Brief cognitive-behavioral training for tinnitus relief using a mobile application: A pilot open trial.}, journal = {Health informatics journal}, volume = {28}, number = {1}, pages = {14604582221083483}, doi = {10.1177/14604582221083483}, pmid = {35349777}, issn = {1741-2811}, mesh = {Cognition ; *Cognitive Behavioral Therapy ; Exercise ; Humans ; *Mobile Applications ; *Tinnitus/psychology/therapy ; }, abstract = {BACKGROUND: Tinnitus may be a disabling, distressing disorder whereby patients report of sounds, in the absence of external stimulus. Recent evidence supports the effectiveness of psychological interventions, particularly, cognitive behavioral therapy (CBT) based intervention for the reduction of tinnitus-related distress and disability. This study assessed the effectiveness of mobile delivered cognitive training exercises to reduce tinnitus-related distress.

MATERIALS AND METHODS: Out of 26 patients diagnosed with tinnitus, 14 participants completed all 48 levels of the app. Levels of pre-post intervention tinnitus intrusiveness and handicap were evaluated using the short Hebrew version of the Tinnitus Handicap Inventory (H-THI). Mood was assessed using a Visual Analogue Scale (VAS). Participants were instructed to complete 3-4 min of daily training for 14 days.

RESULTS: Repeated-measures ANOVA of completers showed a significant large-effect size reduction on H-THI scores. 50% of completers have shown reliable change (indicated by their Reliable Change Index [RCI] scores). No significant change was found in mood.

DISCUSSION: Several minutes a day of training using a CBT-based app targeting maladaptive believes may decreased patients' tinnitus intrusiveness and handicap.

CONCLUSIONS: Mobile apps can provide access to CBT-based interventions, using an efficient, inviting and simple platform, addressing the ramifications of tinnitus symptoms.}, } @article {pmid35348974, year = {2022}, author = {Sivadas, A and Kok, VC and Ng, KL}, title = {Multi-omics analyses provide novel biological insights to distinguish lobular ductal types of invasive breast cancers.}, journal = {Breast cancer research and treatment}, volume = {193}, number = {2}, pages = {361-379}, pmid = {35348974}, issn = {1573-7217}, support = {MOST 109-2221-E-468-013//Ministry of Science and Technology, Taiwan/ ; MOST 108-2221-E-468-020//Ministry of Science and Technology, Taiwan/ ; 07-Asia-02//Asia University Taiwan/ ; 107-Asia-09//Asia University Taiwan/ ; IA/E/19/1/504945//The Wellcome Trust DBT India Alliance/ ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; *Immediate-Early Proteins ; Prognosis ; Receptors, G-Protein-Coupled ; Survival Analysis ; Tumor Suppressor Proteins ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) treatment is similar to invasive ductal carcinoma (IDC; now invasive carcinoma-no special type, IBC-NST), based on its intrinsic subtype. However, further investigation is required for an integrative understanding of differentially perturbed molecular patterns and pathways in these histotypes.

METHODS: A dataset of 780 IDC and 201 ILC samples from the TCGA-BRCA project for cross-platform multi-omics was analyzed. We leveraged a consensus approach integrating different bioinformatic algorithms to analyze mutations, CNAs, mRNA, miRNA abundance, methylation, and protein abundance to understand the complex crosstalks that distinguish ILC and IDC samples. A histotype-matched comparison was performed. We performed Cox survival analyses for prognosis based on our identified 53 histotype-specific and four discordant genes.

RESULTS: Approximately 90% of ILC cases were of the luminal subtype. Somatic mutations in CDH1 were higher in ILC than in IDC (FDR-adjusted p < 0.01). Fifty-three significant oncogenic or tumor-suppressive DEGs were identified in a single histotype. PPAR signaling and lipolysis regulation in adipocytes were significantly enriched in ILC tumors. CDH1 protein had the highest differential abundance (AUC: 0.85). Moreover, BTG2, GSTA2, GPR37L1, and PGBD5 amplification was associated with poorer OS in ILC compared with no alteration. RIMS2, NACA4P, MYC, ZFPM2, and POU5F1B amplification showed a lower overall survival in patients with IDC. miR-195 showed an IDC-specific downregulation, causing overexpression of CCNE1. Integrative multi-omics supervised analysis identified 296 differentially expressed genes that successfully distinguished IDC and ILC histotypes.

CONCLUSIONS: Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.}, } @article {pmid35348061, year = {2021}, author = {Khan, NA and Nguyen, ST and Teh, PG and Ranpura, VN and Bhatia, T}, title = {Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.}, journal = {The Permanente journal}, volume = {25}, number = {}, pages = {}, pmid = {35348061}, issn = {1552-5775}, mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary ; *Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Mammography ; Receptors, Estrogen ; }, abstract = {Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.}, } @article {pmid35347549, year = {2022}, author = {Mouabbi, JA and Hassan, A and Lim, B and Hortobagyi, GN and Tripathy, D and Layman, RM}, title = {Invasive lobular carcinoma: an understudied emergent subtype of breast cancer.}, journal = {Breast cancer research and treatment}, volume = {193}, number = {2}, pages = {253-264}, pmid = {35347549}, issn = {1573-7217}, mesh = {*Breast Neoplasms/diagnosis/epidemiology/therapy ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/therapy ; Female ; Humans ; Prognosis ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer after invasive ductal carcinoma (IDC), accounting for 10-15% of all breast cancer cases. Although most ILCs are of the luminal A intrinsic subtype, with favorable prognostic features, conflicting literature data are available on their outcomes compared to IDC with reports suggesting a higher risk of distant recurrence after 10 years. Historically, studies have combined ILC and IDC, with outcomes largely driven by the behavior of IDC given that it represents 90% of breast cancers. However, over the past 5 years, reports of several studies aimed at understanding ILC at the clinical, cellular, and molecular levels have been published, showing that IDC and ILC are distinct entities. In this review, we highlight the unique characteristics of ILC and describe the need for dedicated ILC clinical trials.}, } @article {pmid35345370, year = {2022}, author = {Henna, N and Rehman, A and Niazi, FB and Sami, W and Aslam, U}, title = {Association of Proliferative Activity in Invasive Ductal Carcinoma Breast in Pakistani Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {3}, pages = {971-975}, pmid = {35345370}, issn = {2476-762X}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Female ; Humans ; Pakistan/epidemiology ; Prognosis ; Prospective Studies ; }, abstract = {Background: Personalized medicine has played very important role in management of breast cancer. Proliferative index is one among the prognostic and predictive factor but unfortunately due to varied reports , no definite consensus and routine medical practice has been approved for it. The objective of the study is to observe the association of Ki-67 index using St. Gallen Conference criteria in invasive ductal carcinoma breast in Pakistani Population. Methods: Eighty-three patients with confirmed light microscopic diagnosis of primary invasive ductal carcinoma were recruited in this prospective study . Expression of Ki67 was determined by classifying as low (<15%) and high (>15%) Ki67 in tumour. Statistical analysis was performed to observe the association of Ki-67 with clinicopathological parameters and molecular group (i.e., Luminal A, Luminal B, Her2 enriched and triple negative). Results: Out of 83 patients, 73.5% of patients showed >15% Ki67 (p value <0.001). High expression of Ki 67 (>15%) was observed in 3.6%, 21.7% and 48.2 % of Nottingham grade I, II and III (p value=0.017) respectively. Among molecular group, high expression of Ki67 was observed 20.5% in Luminal A, 9.6% in Luminal B, 15.7% in Her2 enriched and 27.7% in triple negative groups (p= 0.017). There was no significant association observed in expression of Ki 67 among lymph node stage, tumour stage and Nottingham prognostic index. Conclusion: Higher Ki-67 reactivity is usually associated with higher-grade morphology of tumour. It can act as an independent predictor in assessment of tumour behavior. However, larger validation clinical studies are still required for confirmation of its importance and for routine practice.}, } @article {pmid35343265, year = {2022}, author = {Zhao, CM and Li, LL and Xu, JW and Li, ZW and Shi, P and Jiang, R}, title = {LINC00092 Suppresses the Malignant Progression of Breast Invasive Ductal Carcinoma Through Modulating SFRP1 Expression by Sponging miR-1827.}, journal = {Cell transplantation}, volume = {31}, number = {}, pages = {9636897221086967}, pmid = {35343265}, issn = {1555-3892}, mesh = {*Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; }, abstract = {Breast invasive ductal carcinoma (IDC) is a most common kind of breast cancer (BC), yet to date the corresponding effective therapies are limited. Extensive evidence has indicated that lncRNAs are involved in multiple cancers, and the potential mechanism of lncRNAs, such as LINC00092, mentioned in IDC remains elusive. IDC clinical samples from TCGA database were used to analyze the expression levels of LINC00092, miR-1827 and SFRP1. Kaplan-Meier method was applied to plot the overall survival curves. KEGG and GO were employed to screen the pathway that LINC00092 participated in. Pearson's correlation analysis determined the relationship between LINC00092 and SFRP1. Bioinformatics analysis and dual-luciferase reporter assay examined the association among LINC00092, miR-1827, and SFRP1. Cell counting kit-8, colony formation and transwell assays were performed to detect cell viability, colony formation, and migration and invasion, respectively. Quantitative reverse-transcription polymerase chain reaction and western blot were utilized to investigate the expression at RNA and protein levels. LINC00092 expression was down-regulated in IDC tissues and cells, which was correlated with poor prognosis. Down-regulated LINC00092 facilitated cell proliferation, colony formation, and cell migration and invasion, while up-regulated LINC00092 inhibited cell malignant behaviors. LINC00092/SFRP1 physically bound to miR-1827 in IDC. SFRP1 expression was proportional to LINC00092 expression and inversely proportional to miR-1827 expression. The inhibitory effects of LINC00092 on cell aggressive behaviors were partially regulated by miR-1827/SFRP1. In summary, our results indicated that overexpression of LINC00092 inhibited the development of IDC through modulating miR-1827/SFRP1 axis, suggesting new therapeutic targets to treat IDC.}, } @article {pmid35340411, year = {2022}, author = {Du, W and Miao, Y and Zhang, G and Luo, G and Yang, P and Chen, F and Zhang, B and Yang, C and Li, G and Chang, J}, title = {The Regulatory Role of Neuropeptide Gene Glucagon in Colorectal Cancer: A Comprehensive Bioinformatic Analysis.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {4262600}, pmid = {35340411}, issn = {1875-8630}, mesh = {Biomarkers, Tumor/metabolism ; *Colonic Neoplasms/genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Glucagon/genetics/metabolism ; Humans ; }, abstract = {BACKGROUND: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer.

METHODS: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells.

RESULTS: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells.

CONCLUSIONS: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.}, } @article {pmid35337805, year = {2022}, author = {Rajabi, F and Mozdarani, H}, title = {Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.}, journal = {Experimental and molecular pathology}, volume = {126}, number = {}, pages = {104758}, doi = {10.1016/j.yexmp.2022.104758}, pmid = {35337805}, issn = {1096-0945}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/genetics/radiotherapy ; Environmental Biomarkers ; Female ; Humans ; *MicroRNAs ; ROC Curve ; Radiation Tolerance/genetics ; }, abstract = {Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.}, } @article {pmid35335161, year = {2022}, author = {Wen, M and Erb, W and Mongin, F and Halauko, YS and Ivashkevich, OA and Matulis, VE and Roisnel, T}, title = {Synthesis of Polysubstituted Ferrocenesulfoxides.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {6}, pages = {}, pmid = {35335161}, issn = {1420-3049}, support = {Ferrodance project//Agence Nationale de la Recherche/ ; 1/CX/CSRD VA/United States ; }, mesh = {*Halogens ; Indicators and Reagents ; Metallocenes ; Stereoisomerism ; }, abstract = {The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe3, PPh2) S-tert-butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe3, I, D, C(OH)Ph2, Me, PPh2, CH2NMe2, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the "halogen dance" reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated pKa values. Further functionalizations were also possible. Thus, new enantiopure, planar chiral di- and trisubstituted ferrocenes have been obtained, in addition to several original 2-substituted, 2,3- and 2,5-disubstituted, 2,3,5-trisubstituted and even 2,3,4,5-tetrasubstituted ferrocenesulfoxides, also enantiopure.}, } @article {pmid35332139, year = {2022}, author = {Griessinger, J and Schwab, J and Chen, Q and Kühn, A and Cotton, J and Bowden, G and Preibsch, H and Reischl, G and Quintanilla-Martinez, L and Mori, H and Dang, AN and Kohlhofer, U and Aina, OH and Borowsky, AD and Pichler, BJ and Cardiff, RD and Schmid, AM}, title = {Intratumoral in vivo staging of breast cancer by multi-tracer PET and advanced analysis.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {41}, pmid = {35332139}, issn = {2374-4677}, support = {EXC-2180 - 390900677//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; ZUK 63//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, abstract = {The staging and local management of breast cancer involves the evaluation of the extent and completeness of excision of both the invasive carcinoma component and also the intraductal component or ductal carcinoma in situ. When both invasive ductal carcinoma and coincident ductal carcinoma in situ are present, assessment of the extent and localization of both components is required for optimal therapeutic planning. We have used a mouse model of breast cancer to evaluate the feasibility of applying molecular imaging to assess the local status of cancers in vivo. Multi-tracer positron emission tomography (PET) and magnetic resonance imaging (MRI) characterize the transition from premalignancy to invasive carcinoma. PET tracers for glucose consumption, membrane synthesis, and neoangiogenesis in combination with a Gaussian mixture model-based analysis reveal image-derived thresholds to separate the different stages within the whole-lesion. Autoradiography, histology, and quantitative image analysis of immunohistochemistry further corroborate our in vivo findings. Finally, clinical data further support our conclusions and demonstrate translational potential. In summary, this preclinical model provides a platform for characterizing multistep tumor progression and provides proof of concept that supports the utilization of advanced protocols for PET/MRI in clinical breast cancer imaging.}, } @article {pmid35330465, year = {2022}, author = {Lello, S and Capozzi, A and Scardina, L and Ionta, L and Sorge, R and Scambia, G and Franceschini, G}, title = {Vitamin D and Histological Features of Breast Cancer: Preliminary Data from an Observational Retrospective Italian Study.}, journal = {Journal of personalized medicine}, volume = {12}, number = {3}, pages = {}, pmid = {35330465}, issn = {2075-4426}, abstract = {Background: Vitamin D (vitD) may be involved in different extraskeletal conditions as well as skeletal muscle diseases. It has been hypothesized that, at least in part, a low level of vitD could contribute to facilitating cancer development. Breast cancer (BC) seems to be associated with low levels of vitD. Materials and methods: This was an observational retrospective evaluation of 87 women (mean age: 54 ± 12 years old) who underwent surgery for the treatment of BC. Our main purpose was to correlate the types of BC and the levels of vitD. Results: A positive significant correlation (R > 0.7) was found between non-invasive carcinoma in situ and 25(OH)D levels and age (R = 0.82, p < 0.05). A positive, but nonsignificant, correlation was reported between invasive ductal carcinoma and 25(OH)D and age (R = 0.45, p > 0.05). A negative but nonsignificant correlation was found between invasive lobular carcinoma and 25(OH)D and age (R = 0.24, p > 0.05). Discussion and Conclusions: We did not find a significant relationship between vitD and BC subtypes. Considering the positive significant correlation between vitD levels and age for in situ BC, although preliminary, our results seem to suggest a possible role of vitD in in situ BC. However, these findings need to be confirmed in larger studies.}, } @article {pmid35328247, year = {2022}, author = {Jo, JH and Chung, HW and So, Y and Yoo, YB and Park, KS and Nam, SE and Lee, EJ and Noh, WC}, title = {FDG PET/CT to Predict Recurrence of Early Breast Invasive Ductal Carcinoma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {35328247}, issn = {2075-4418}, abstract = {This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence.}, } @article {pmid35324454, year = {2022}, author = {Wang, K and Schütze, I and Gulde, S and Bechmann, N and Richter, S and Helm, J and Lauseker, M and Maurer, J and Reul, A and Spoettl, G and Klink, B and William, D and Knösel, T and Friemel, J and Bihl, M and Weber, A and Fankhauser, M and Schober, L and Vetter, D and Broglie Däppen, M and Ziegler, CG and Ullrich, M and Pietzsch, J and Bornstein, SR and Lottspeich, C and Kroiss, M and Fassnacht, M and Wenter, VUJ and Ladurner, R and Hantel, C and Reincke, M and Eisenhofer, G and Grossman, AB and Pacak, K and Beuschlein, F and Auernhammer, CJ and Pellegata, NS and Nölting, S}, title = {Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.}, journal = {Endocrine-related cancer}, volume = {29}, number = {6}, pages = {285-306}, doi = {10.1530/ERC-21-0355}, pmid = {35324454}, issn = {1479-6821}, mesh = {*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism ; Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Everolimus/therapeutic use ; Humans ; Mice ; *Paraganglioma/drug therapy/genetics/pathology ; *Pheochromocytoma/drug therapy/genetics/metabolism ; Zoledronic Acid/therapeutic use ; }, abstract = {Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.}, } @article {pmid35317367, year = {2021}, author = {Ozdemir, O and Zengel, B and Yildiz, Y and Saray, S and Alacacioglu, A and Tasli, F and Can Erdi, Z and Oflazoglu, U and Taskaynatan, H and Salman, T and Varol, U and Hilal Adibelli, Z and Durusoy, R and Kucukzeybek, Y}, title = {Neuroendocrine Differentiated Breast Cancer Cases: A Retrospective Analysis and Literature Review.}, journal = {Sisli Etfal Hastanesi tip bulteni}, volume = {55}, number = {4}, pages = {503-509}, pmid = {35317367}, issn = {1302-7123}, abstract = {OBJECTIVES: Neuroendocrine breast carcinoma (NEBC) is a rare subgroup of breast cancer, which makes up 2-5% of all invasive breast cancers. The aim of this retrospective analysis is to present and analyze our own data of primary NEBCs.

METHODS: We retrospectively analyzed clinical, pathological, and radiological characteristics of 36 patients diagnosed with neuroendocrine differentiated breast cancer between 2008 and 2019 compared to that of 925 patients with invasive ductal carcinoma (IDC/NOS) along with a literature review.

RESULTS: In this study, 36 patients with neuroendocrine differentiated breast carcinoma and 961 patients with (IDC/NOS), as the comparison group, were identified between 2008 and 2019. In NEBC patients, seven were premenopausal and 29 postmenopausal. Patients whose ultrasound (USG), magnetic resonance, and mammographic (MMG) images available in our hospital, high-density masses were detected in the MMG with irregular (77%), microlobulated (80%) and spiculated margins (63%), unaccompanied by asymmetry and structural distortion. Calcifications were less common than invasive breast cancer, present only in four patients (17%). When NEBC were compared to ductal carcinomas (n=925), NEBC were more often human epidermal growth factor receptor 2 negative (p=0.039), estrogen receptor positive (p=0.05), progesterone receptor positive (0.03), and the NEBC patients were older (p=0.02). Age, grade, metastatic status, lymph node number, and molecular type were identified as prognostic factors that significantly affect survival in both groups (p<0.05).

CONCLUSION: NEBC is a subtype that is both histopathologically and radiologically distinct from other breast cancer subtypes, and neuroendocrine differentiation may be an important predictive marker in the future.}, } @article {pmid35313896, year = {2022}, author = {Merry, R and Espina, MJ and Lorenz, AJ and Stupar, RM}, title = {Development of a controlled-environment assay to induce iron deficiency chlorosis in soybean by adjusting calcium carbonates, pH, and nodulation.}, journal = {Plant methods}, volume = {18}, number = {1}, pages = {36}, pmid = {35313896}, issn = {1746-4811}, abstract = {BACKGROUND: Soybean iron deficiency chlorosis (IDC) is an important nutrient stress frequently found in high pH and/or soils high in calcium carbonates. To advance the understanding of IDC resistance in soybean, a rapid (21-day) controlled-environment assay was developed to investigate the effects of nodulation, pH, and calcium carbonate levels on soybean iron deficiency traits. This system was tested on four genotypes known to exhibit differences in iron efficiency, including two standard IDC check cultivars and a pair of near-isogenic lines exhibiting variation at an IDC resistance quantitative trait locus. Visual score, chlorophyll content, plant height, root dry mass, and shoot dry mass were measured to quantify iron stress.

RESULTS: Calcium carbonate levels and nodulation were found to have the greatest effects on IDC severity. Increasing calcium carbonate levels worsened IDC symptoms, while nodulation reduced symptoms in all genotypes. Higher pH levels increased iron deficiency symptoms in check genotypes 'Corsoy 79' and 'Dawson', but did not induce iron deficiency symptoms in near-isogenic lines. A significant interaction was observed between genotype, nodulation, and calcium carbonate level, indicating that a specific treatment level could discern IDC symptoms between genotypes differing in resistance to IDC.

CONCLUSIONS: IDC symptoms were successfully induced in the Check Genotypes Experiment as well as the NIL Experiment, indicating the success of using this assay for inducing IDC in controlled environments. However, our results suggest that treatment levels that best differentiate genotypes for their IDC resistance may need to be determined for each experiment because of the unique way in which different genotypes display symptoms and respond to iron deficiency conditions.}, } @article {pmid35312051, year = {2022}, author = {Turk, E and Vroomen, J and Fonken, Y and Levy, J and van den Heuvel, MI}, title = {In sync with your child: The potential of parent-child electroencephalography in developmental research.}, journal = {Developmental psychobiology}, volume = {64}, number = {3}, pages = {e22221}, doi = {10.1002/dev.22221}, pmid = {35312051}, issn = {1098-2302}, mesh = {*Brain/physiology ; *Electroencephalography/methods ; Humans ; Parent-Child Relations ; Parents/psychology ; }, abstract = {Healthy interaction between parent and child is foundational for the child's socioemotional development. Recently, an innovative paradigm shift in electroencephalography (EEG) research has enabled the simultaneous measurement of neural activity in caregiver and child. This dual-EEG or hyperscanning approach, termed parent-child dual-EEG, combines the strength of both behavioral observations and EEG methods. In this review, we aim to inform on the potential of dual-EEG in parents and children (0-6 years) for developmental researchers. We first provide a general overview of the dual-EEG technique and continue by reviewing the first empirical work on the emerging field of parent-child dual-EEG, discussing the limited but fascinating findings on parent-child brain-to-behavior and brain-to-brain synchrony. We then continue by providing an overview of dual-EEG analysis techniques, including the technical challenges and solutions one may encounter. We finish by discussing the potential of parent-child dual-EEG for the future of developmental research. The analysis of multiple EEG data is technical and challenging, but when performed well, parent-child EEG may transform the way we understand how caregiver and child connect on a neurobiological level. Importantly, studying objective physiological measures of parent-child interactions could lead to the identification of novel brain-to-brain synchrony markers of interaction quality.}, } @article {pmid35311108, year = {2022}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {708632}, pmid = {35311108}, issn = {2234-943X}, abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

PATIENTS AND METHODS: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT.

CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.}, } @article {pmid35310217, year = {2022}, author = {Schori-Eyal, N and Sobol-Sarag, D and Shuman, E and Halperin, E}, title = {Shamed If You Do, Shamed If You Do Not: Group-Based Moral Emotions, Accountability, and Tolerance of Enemy Collateral Casualties.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {750548}, pmid = {35310217}, issn = {1664-1078}, abstract = {Civilian casualties contribute to the perpetuation of intergroup conflicts through increased radicalization and hostilities, but little is known on the psychological processes that affect responses to outgroup civilian casualties. The goal of the present research was to explore two factors expected to lead group members to act more cautiously, thereby reducing civilian casualties: perceived accountability and forecast group-based moral emotions. In two studies, Jewish-Israeli civilians (Study 1) and soldiers (Study 2) were asked to forecast their group-based moral emotions in case of Palestinian (i.e., outgroup) civilian casualties, then exposed to accountability manipulations. Participants who expected to feel low levels of shame and were primed with accountability made more cautious decisions than those in the control condition. Participants who expected to feel high levels of shame were unaffected by accountability primes. Theoretical and practical implications regarding forecast moral emotions and accountability as an intervention in intergroup conflicts are discussed.}, } @article {pmid35308412, year = {2023}, author = {Shenkman, G and Carone, N and Mouton, B and d'Amore, S and Bos, HMW}, title = {Assisted Conception Socialization Self-Efficacy Among Israeli Lesbian, Gay, and Heterosexual Parent Families and its Association with Child Externalizing Problems.}, journal = {Journal of child and family studies}, volume = {32}, number = {1}, pages = {180-196}, pmid = {35308412}, issn = {1062-1024}, abstract = {This questionnaire-based study compared 36 Israeli lesbian mother families (n = 72 lesbian mothers) formed by donor insemination, 39 Israeli gay father families (n = 78 gay fathers) formed by gestational surrogacy, and 36 Israeli heterosexual parent families (n = 72 heterosexual parents) formed by assisted reproduction (without donated gametes), all with a target child aged 3-10 years. The families were examined for parents' assisted conception socialization self-efficacy, depression, negative and positive affect, life satisfaction, positivity, resilience, social support, and child externalizing problems. Multiple factors associated with child externalizing problems were also examined. Multilevel modeling analyses indicated that parents' assisted conception socialization self-efficacy did not differ between family groups; however, lesbian mothers and gay fathers reported fewer child externalizing problems and greater social support, relative to heterosexual parents. Also, lesbian mothers-but not gay fathers-reported lower levels of depression, greater life satisfaction, and more positivity than did heterosexual parents. Finally, irrespective of family type, greater assisted conception socialization self-efficacy was associated with fewer parent-reported child externalizing problems. Findings are interpreted in light of the cultural socialization framework and Israel's familistic and pronatalist environment. Implications for health professionals, educators, and policymakers working with diverse family forms are discussed.}, } @article {pmid35300617, year = {2022}, author = {Chan, KS and Cheung, SM and Senn, N and Husain, E and Masannat, Y and Heys, S and He, J}, title = {Peri-tumoural spatial distribution of lipid composition and tubule formation in breast cancer.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {285}, pmid = {35300617}, issn = {1471-2407}, support = {C68628/A28312/CRUK_/Cancer Research UK/United Kingdom ; 1654748//BBSRC EASTBIO scholarship/ ; 15/1/052//NHS Grampian Endowment Research Fund/ ; }, mesh = {Adult ; Aged ; Breast/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/*metabolism ; Cross-Sectional Studies ; Entropy ; Fatty Acids/*metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymphocytes, Tumor-Infiltrating/metabolism ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {BACKGROUND: Response guided treatment in breast cancer is highly desirable, but the effectiveness is only established based on residual cellularity from histopathological analysis after surgery. Tubule formation, a key component of grading score, is directly associated with cellularity, with significant implications on prognosis. Peri-tumoural lipid composition, a potential marker, can be rapidly mapped across the entire breast using novel method of chemical shift-encoded imaging, enabling the quantification of spatial distribution. We hypothesise that peri-tumoural spatial distribution of lipid composition is sensitive to tumour cellular differentiation and proliferative activity.

METHODS: Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma (9 Score 2 and 11 Score 3 in tubule formation) were scanned on a 3 T clinical scanner (Achieva TX, Philips Healthcare). Quantitative lipid composition maps were acquired for polyunsaturated, monounsaturated, and saturated fatty acids (PUFA, MUFA, SFA). The peri-tumoural spatial distribution (mean, skewness, entropy and kurtosis) of each lipid constituent were then computed. The proliferative activity marker Ki-67 and tumour-infiltrating lymphocytes (TILs) were assessed histologically.

RESULTS: For MUFA, there were significant differences between groups in mean (p = 0.0119), skewness (p = 0.0116), entropy (p = 0.0223), kurtosis (p = 0.0381), and correlations against Ki-67 in mean (ρ = -0.5414), skewness (ρ = 0.6045) and entropy (ρ = 0.6677), and TILs in mean (ρ = -0.4621). For SFA, there were significant differences between groups in mean (p = 0.0329) and skewness (p = 0.0111), and correlation against Ki-67 in mean (ρ = 0.5910). For PUFA, there was no significant difference in mean, skewness, entropy or kurtosis between the groups.

CONCLUSIONS: There was an association between peri-tumoural spatial distribution of lipid composition with tumour cellular differentiation and proliferation. Peri-tumoural lipid composition imaging might have potential in non-invasive quantitative assessment of patients with breast cancer for treatment planning and monitoring.}, } @article {pmid35300231, year = {2022}, author = {Sae-Kho, TM and Bhatt, A and Solanki, MH and Jeans, EB and Corbin, KS and Fazzio, RT and Glazebrook, KN}, title = {Imaging features of adenosquamous carcinoma of the breast - A rare variant of metaplastic breast carcinoma.}, journal = {BJR case reports}, volume = {7}, number = {6}, pages = {20210108}, pmid = {35300231}, issn = {2055-7159}, abstract = {Adenosquamous carcinoma of the breast is a rare subtype of metaplastic carcinoma, which accounts for <1% of invasive breast malignancy. Metaplastic carcinoma is usually high grade and aggressive with typically reported benign imaging features when compared to invasive ductal carcinoma. However, the adenosquamous variant is a subtype with a more favorable prognosis. Within the literature, there is limited imaging description with case studies focusing on metaplastic carcinoma. Herein, we report seven cases of the adenosquamous subtype describing the imaging findings with correlation to clinical history and pathology. The majority of patients (n = 6) presented with palpable breast masses. One patient was identified through screening mammography. Mammographically (n = 6), tumors appeared as irregular masses. Sonographically (n = 7), tumors appeared as irregular masses ranging from solid to mixed solid/cystic masses. On MRI (n = 1), one tumor appeared as an irregular rim enhancing mass. FDG PET/CT (n = 2) and whole-body bone scan (n = 1) were also available for review. The majority of tumors were low-grade (n = 6) with only one high-grade tumor. This case series of seven patients demonstrated predominantly suspicious imaging features despite the majority being low-grade tumors.}, } @article {pmid35299943, year = {2022}, author = {Amboni, M and Ricciardi, C and Cuoco, S and Donisi, L and Volzone, A and Ricciardelli, G and Pellecchia, MT and Santangelo, G and Cesarelli, M and Barone, P}, title = {Mild Cognitive Impairment Subtypes Are Associated With Peculiar Gait Patterns in Parkinson's Disease.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {781480}, pmid = {35299943}, issn = {1663-4365}, abstract = {BACKGROUND: Mild cognitive impairment (MCI) is frequent in Parkinson's disease (PD) and represents a risk factor for the development of dementia associated with PD (PDD). Since PDD has been associated with disability, caregiver burden, and an increase in health-related costs, early detection of MCI associated with PD (PD-MCI) and its biomarkers is crucial.

OBJECTIVE: Given that gait is considered a surrogate marker for cognitive decline in PD, the aim of this study was to compare gait patterns in PD-MCI subtypes in order to verify the existence of an association between specific gait features and particular MCI subtypes.

METHODS: A total of 67 patients with PD were consecutively enrolled and assessed by an extensive clinical and cognitive examination. Based on the neuropsychological examination, patients were diagnosed as patients with MCI (PD-MCI) and without MCI (no-PD-MCI) and categorized in MCI subtypes. All patients were evaluated using a motion capture system of a BTS Bioengineering equipped with six IR digital cameras. Gait of the patients was assessed in the ON-state under three different tasks (a single task and two dual tasks). Statistical analysis included the t-test, the Kruskal-Wallis test with post hoc analysis, and the exploratory correlation analysis.

RESULTS: Gait pattern was poorer in PD-MCI vs. no-PD-MCI in all tasks. Among PD-MCI subtypes, multiple-domain PD-MCI and amnestic PD-MCI were coupled with worse gait patterns, notably in the dual task.

CONCLUSION: Both the magnitude of cognitive impairment and the presence of memory dysfunction are associated with increased measures of dynamic unbalance, especially in dual-task conditions, likely mirroring the progressive involvement of posterior cortical networks.}, } @article {pmid35292677, year = {2022}, author = {Kao, Y and Wu, YJ and Hsu, CC and Lin, HJ and Wang, JJ and Tian, YF and Weng, SF and Huang, CC}, title = {Short- and long-term recurrence of early-stage invasive ductal carcinoma in middle-aged and old women with different treatments.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {4422}, pmid = {35292677}, issn = {2045-2322}, mesh = {*Breast Neoplasms/epidemiology/pathology/therapy ; *Carcinoma, Ductal/pathology ; *Carcinoma, Ductal, Breast/epidemiology/therapy ; Cohort Studies ; Female ; Humans ; Male ; Mastectomy/methods ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; }, abstract = {Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36-2.66] vs. 2.07 [95% CI 0.97-4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26-0.35] vs. 0.43 [95% CI 0.30-0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.}, } @article {pmid35292141, year = {2022}, author = {Rebollo Aguirre, AC and Fernández Fernández, J and Sánchez Sánchez, R and Mendoza Arnau, I and Rivas Navas, DJ and Martínez Meca, S}, title = {Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {41}, number = {2}, pages = {71-77}, doi = {10.1016/j.remnie.2021.04.017}, pmid = {35292141}, issn = {2253-8089}, mesh = {Adult ; Aged ; *Breast Neoplasms/diagnostic imaging/drug therapy/surgery ; Female ; Humans ; Iodine Radioisotopes/therapeutic use ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Prospective Studies ; *Surgery, Computer-Assisted ; *Thyroid Neoplasms/surgery ; }, abstract = {OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC).

MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7 ± 11.4 years. Tumor size: 34.1 ± 14.6 mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%.

RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7 ± 111.2 cm[3]. Of the 5 s local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients.

CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.}, } @article {pmid35285011, year = {2022}, author = {Bai, Y and Lu, J and Wu, H and Wang, J and Niu, Y and Pang, J and Wu, S and Liu, Y and Liang, Z}, title = {A comparative clinicopathological and survival analysis of synchronous bilateral breast cancers.}, journal = {Histology and histopathology}, volume = {37}, number = {8}, pages = {791-802}, pmid = {35285011}, issn = {1699-5848}, support = {2016-I2M-1-002//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease-Free Survival ; Female ; Humans ; Prognosis ; Survival Analysis ; }, abstract = {OBJECTIVE: The present study aimed to explore the clinicopathological characteristics, potential heterogeneity and prognostic factors in synchronous bilateral breast cancer (SBBC).

METHODS: We performed a retrospective review and paired comparison of the clinicopathological characteristics of 114 patients with SBBC in the Peking Union Medical College Hospital from January 2008 to September 2019. The prognostic significance of triple negativity status and coexistence ductal carcinoma in situ (DCIS) with bilateral invasive ductal carcinomas of no special type (IDC-NST) was analyzed in SBBC.

RESULTS: Most bilateral lesions on both sides were of IDC-NST, grade 2, luminal subtype, and stage I. Although most lesions were concordant between the left and right side, discordances were observed in histological type (25 cases, 21.9%), histological grade (31 cases, 27.2%), pTNM (61 cases, 53.5%), molecular subtypes (20 cases, 17.5%), and immunohistochemical staining of ER (18 cases, 15.8%), PR (26 cases, 22.8%), and HER2 (12 cases, 10.5%). Moreover, there was no significant difference in disease-free survival (DFS) and overall survival (OS) between IDC-NST with coexisting DCIS on both sides and IDC-NST with coexisting DCIS on one side or pure IDC-NST. SBBC with triple negativity on both sides exhibited a significantly shorter DFS and OS when compared with triple negativity on one side or non-triple negativity on both sides (p<0.001), and remained an independent prognostic factor by multivariate analysis.

CONCLUSIONS: A considerable proportion of discordance in clinicopathological characteristics is observed in SBBC, supporting the necessity of comprehensive pathological examination including immunohistochemical testing on both sides in clinical practice. Moreover, SBBC with triple negativity on both sides is a prognostic for poor survival.}, } @article {pmid35284300, year = {2022}, author = {Zhou, M and Jiang, L and Fan, Y and Ma, T and Wang, Y and Wang, X}, title = {Correlation between circulating tumor cells and different molecular biological characteristics in breast cancer patients.}, journal = {Gland surgery}, volume = {11}, number = {2}, pages = {466-471}, pmid = {35284300}, issn = {2227-684X}, abstract = {BACKGROUND: This study sought to detect the number of circulating tumor cells (CTCs) in breast cancer patients, and examine the relationship between CTCs and molecular biological characteristics.

METHODS: From June 2016 to June 2018, 150 female patients with invasive breast cancer detected by CTCs at the Department of Breast Surgery, Fudan University Cancer Hospital were enrolled in this study. The patients had an average age of 52.6±7.8 (range, 35-77) years. Routine pathological and immunohistochemical examinations were performed on tissues obtained during surgery. In this study, CTCs were detected using the immunomagnetic bead negative enrichment technique (i.e., the Cyttel technique). The measurement data are expressed by x ± s, and were compared by t-tests. A univariate analysis of variance was used to compare differences between groups. The count data are expressed as the absolute value, and the test χ[2] or Fisher's exact test were used to compare differences.

RESULTS: There were 109 cases of positive CTC (≥3 CTCs/4 mL) (72.7%), and 41 cases of negative CTC (<3 CTCs/4 mL) (27.3%). There were no significant differences in terms of age and menopausal status between the two groups (P>0.05). There was no significant difference in the positive rate of CTC in T1, T2, and T3 and above patients (P>0.05). There was no significant difference in the CTC positive rate between ER positive and negative patients, PR positive and negative patients, and Ki-67 ≥14% and <14% patients (P>0.05). However, there was a statistical difference in the positive rate of CTC between human epidermal growth factor receptor 2 (HER-2) positive and negative patients (P<0.05). There was no significant difference in the CTC positive rate among patients with Luminal A type, B type, HER-2 overexpression type, and triple negative breast cancer (TNBC) (P>0.05). There was no significant difference in the positive rate of CTC among patients with invasive ductal carcinoma, invasive lobular carcinoma, and other types of invasive carcinoma (P>0.05).

CONCLUSIONS: It can be concluded that there is a relationship between CTC and HER-2 expression, which has certain predictive value for patients with positive HER-2 expression, thus predicting poor prognosis.}, } @article {pmid35284250, year = {2022}, author = {Cho, E and Baek, HJ and Szczepankiewicz, F and An, HJ and Jung, EJ and Lee, HJ and Lee, J and Gho, SM}, title = {Clinical experience of tensor-valued diffusion encoding for microstructure imaging by diffusional variance decomposition in patients with breast cancer.}, journal = {Quantitative imaging in medicine and surgery}, volume = {12}, number = {3}, pages = {2002-2017}, pmid = {35284250}, issn = {2223-4292}, abstract = {BACKGROUND: Diffusion-weighted imaging plays a key role in magnetic resonance imaging (MRI) of breast tumors. However, it remains unclear how to interpret single diffusion encoding with respect to its link with tissue microstructure. The purpose of this retrospective cross-sectional study was to use tensor-valued diffusion encoding to investigate the underlying microstructure of invasive ductal carcinoma (IDC) and evaluate its potential value in a clinical setting.

METHODS: We retrospectively reviewed biopsy-proven breast cancer patients who underwent preoperative breast MRI examination from July 2020 to March 2021. We reviewed the MRI of 29 patients with 30 IDCs, including analysis by diffusional variance decomposition enabled by tensor-valued diffusion encoding. The diffusion parameters of mean diffusivity (MD), total mean kurtosis (MKT), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), macroscopic fractional anisotropy (FA), and microscopic fractional anisotropy (µFA) were estimated. The parameter differences were compared between IDC and normal fibroglandular breast tissue (FGBT), as well as the association between the diffusion parameters and histopathologic items.

RESULTS: The mean value of MD in IDCs was significantly lower than that of normal FGBT (1.07±0.27 vs. 1.34±0.29, P<0.001); however, MKT, MKA, MKI, FA, and µFA were significantly higher (P<0.005). Among all the diffusion parameters, MKI was positively correlated with the tumor size on both MRI and pathological specimen (rs=0.38, P<0.05 vs. rs=0.54, P<0.01), whereas MKT had a positive correlation with the tumor size in the pathological specimen only (rs=0.47, P<0.02). In addition, the lymph node (LN) metastasis group had significantly higher MKT, MKA, and µFA compared to the metastasis negative group (P<0.05).

CONCLUSIONS: Tensor-valued diffusion encoding enables a useful non-invasive method for characterizing breast cancers with information on tissue microstructures. Particularly, µFA could be a potential imaging biomarker for evaluating breast cancers prior to surgery or chemotherapy.}, } @article {pmid35284127, year = {2022}, author = {Mo, J and Zhang, J and Huang, H and Liu, C and Cheng, Y and Mo, Y and Wu, S and Zhong, Y and Zhong, C and Zhang, B}, title = {The early predictive effect of low expression of the ITGA4 in colorectal cancer.}, journal = {Journal of gastrointestinal oncology}, volume = {13}, number = {1}, pages = {265-278}, pmid = {35284127}, issn = {2078-6891}, abstract = {BACKGROUND: The early diagnosis of colorectal cancer (CRC) is very important for the prognosis of patients. It has been suggested that the cytosine-phosphate-guanine (CpG) island of itga4 is highly methylated in colorectal adenoma cell lines AA/C1, Vaco 235 and so on. So the purpose of our study is to explore the diagnostic accuracy and related mechanism of integrin alpha 4 (ITGA4) in early CRC.

METHODS: The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between the expression of ITGA4 and the clinicopathological features and the overall survival rate of the disease. Then, the interaction protein and function enrichment region of ITGA4 were analyzed. Finally, the infiltration of related immune cells was analyzed.

RESULTS: Compared with normal tissues, the expression of ITGA4 in colon adenocarcinoma and rectum adenocarcinoma (COAD-READ) tumor tissues was lower (P<0.05). The overall survival rate of COAD-READ patients with low ITGA4 level was lower than that of patients with high ITGA4 expression (P<0.05), and expression of ITGA4 had a more significant predictive effect in the early stage of tumor development. The results of protein network and enrichment analysis suggested that ITGA4 was closely related to ITGB2 and might be involved in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of inflammatory bowel disease (IBD), which was verified by another independent sequence. In terms of immune infiltration, the expression level of ITGA4 was positively correlated with the infiltration level of intestinal macrophages (Th17), immature dendritic cells (IDC), dendritic cells (DC), mast cells, and eosinophils in COAD-READ, and significantly negatively correlated with CD56[bright] natural killer (NK) cells.

CONCLUSIONS: The low expression of ITGA4 was related to the poor prognosis of COAD-READ. Findings showed that ITGA4 might participate in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of IBD, and that ITGA4 was related to the infiltration of immune cells, macrophages, syndactyls, and CD56[bright] NK cells. The expression of ITGA4 could be used as an early predictor of CRC. However, the mechanism of ITGA4 promoting tumor progression in CRC still needs further research.}, } @article {pmid35278202, year = {2022}, author = {Nakayama, S and Masuda, H and Miura, S and Kuwayama, T and Hashimoto, R and Taruno, K and Sawada, T and Akashi-Tanaka, S and Nakamura, S}, title = {Identifying ductal carcinoma in situ cases not requiring surgery to exclude postoperative upgrade to invasive ductal carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {29}, number = {4}, pages = {610-617}, pmid = {35278202}, issn = {1880-4233}, mesh = {*Breast Neoplasms/surgery ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Female ; Humans ; Prognosis ; Prospective Studies ; }, abstract = {BACKGROUND: Prospective cohort studies are being conducted worldwide to identify a low-grade group of ductal carcinoma in situ (DCIS) that does not require surgery. However, to do this, it is necessary to predict which cases, diagnosed with preoperative DCIS, will be upgraded to invasive ductal carcinoma (IDC) after surgery.

METHODS: In this study, we evaluated the frequency of IDC upgrades in patients who were preoperatively diagnosed with DCIS at Showa University using the criteria of ongoing clinical trials. We divided our cases into those that could be enrolled in the ongoing trial and those that could not. Moreover, we evaluated whether CNB, which is allowed only in Japanese clinical trials, is related to the IDC mixture.

RESULTS: There were 211 (52.1%) cases that matched the criteria of the U.K. and Netherlands trials, of which 62 (29.4%) were upgraded to IDC. A total of 113 (27.9%) cases met the criteria for clinical trials in Japan and the U.S., 25 (22.1%) of which were upgraded to IDC and 47 (34.6%) which matched when considering biopsy methods. The number of cases upgraded to IDC decreased to four (8.5%).

CONCLUSIONS: This study demonstrated that there were a certain number of mixed IDC. We will pay attention to the results of ongoing clinical trials regarding how the presence of this mixed IDC affects the prognosis in non-surgery cases. Careful follow-up is recommended for non-surgical treatment.}, } @article {pmid35277835, year = {2022}, author = {Sheaffer, R and Levy, DA}, title = {Negative recency effects in delayed recognition: Spacing, consolidation, and retrieval strategy processes.}, journal = {Memory & cognition}, volume = {50}, number = {8}, pages = {1683-1693}, pmid = {35277835}, issn = {1532-5946}, mesh = {Humans ; *Recognition, Psychology ; *Mental Recall ; Memory, Short-Term ; Memory, Long-Term ; }, abstract = {While items learned immediately before testing are generally remembered better than prior items in a study list, in delayed testing this relationship is reversed, yielding a negative recency effect. To adjudicate between the strategic rehearsal and spacing accounts of this phenomenon, we examined performance of 169 participants on a delayed recognition test following multiple sessions requiring the study and immediate free recall testing of 16 lists of 16 words. This revealed a strong effect of the amount of spacing between initial study position and initial free recall position on the degree of negative recency, supporting the spacing account. Furthermore, these spacing effects were nonmonotonic, suggesting that they are mediated by consolidation processes. Additional analyses indicate that strategies and rehearsal opportunities may also contribute to the effects of within-list encoding position on subsequent long-term memory, but for recall more than for recognition.}, } @article {pmid35272171, year = {2022}, author = {Acikgoz, E and Duzagac, F and Guven, U and Yigitturk, G and Kose, T and Oktem, G}, title = {"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108684}, doi = {10.1016/j.intimp.2022.108684}, pmid = {35272171}, issn = {1878-1705}, mesh = {Animals ; *Cancer Vaccines/therapeutic use ; Dendritic Cells ; Mice ; N-Acetylneuraminic Acid ; *Neoplasms ; Neoplastic Stem Cells ; }, abstract = {Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44[+]/CD24[-/low] breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.}, } @article {pmid35266635, year = {2022}, author = {Karabid, NM and Wiedemann, T and Gulde, S and Mohr, H and Segaran, RC and Geppert, J and Rohm, M and Vitale, G and Gaudenzi, G and Dicitore, A and Ankerst, DP and Chen, Y and Braren, R and Kaissis, G and Schilling, F and Schillmaier, M and Eisenhofer, G and Herzig, S and Roncaroli, F and Honegger, JB and Pellegata, NS}, title = {Angpt2/Tie2 autostimulatory loop controls tumorigenesis.}, journal = {EMBO molecular medicine}, volume = {14}, number = {5}, pages = {e14364}, pmid = {35266635}, issn = {1757-4684}, mesh = {*Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Heterografts ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Pituitary Neoplasms/genetics/metabolism/pathology ; Rats ; Receptor, TIE-2/genetics/metabolism ; Zebrafish ; }, abstract = {Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.}, } @article {pmid35262438, year = {2022}, author = {Jones, VM and Pearce, JB and Khalil, M and Cain, O and Coldren, D and Martin, H and Howard-McNatt, M and Levine, E and Chiba, A}, title = {Upstage Rate of Complex Sclerosing Lesions/Radial Scars.}, journal = {The American surgeon}, volume = {88}, number = {5}, pages = {964-967}, doi = {10.1177/00031348211056282}, pmid = {35262438}, issn = {1555-9823}, mesh = {Biopsy, Large-Core Needle/methods ; Breast/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology/surgery ; Cicatrix/pathology ; Female ; Humans ; Mammography ; Retrospective Studies ; }, abstract = {BACKGROUND: Radial scars (RS) and complex sclerosing lesions (CSL) are breast radiologic findings described as small, stellate lesions causing architectural distortion. This can mimic malignancy. Core needle biopsy (CNB) is often performed. Advances in breast imaging have led to increased detection of RS/CSL. The upstage rate of RS/CSL to in situ or invasive disease is 0-40%. We sought to determine the upstaging rate of RS/CSL to in situ, invasive disease, or high-risk lesion at our institution to create excision guidelines.

METHODS: The pathology database of a single center was searched for RS/CSL, from January 2013 to September 2020. We included CNB without malignancy or high-risk lesion (eg, atypical ductal hyperplasia). Patient demographics, indications for biopsy, imaging findings, biopsy procedure, and final pathology were collected.

RESULTS: Forty-four patients were included. 52.3% had CNB for architectural distortion on mammography, 18.2% for mass, 11.4% for calcifications, 2.3% for abnormal MRI, and 15.9% for multiple reasons (eg, calcifications and mass). Most had an ultrasound: 43.2% had no abnormality and 34.1% had a mass. All CNB were vacuum assisted, 65.9% with 9-gauge needle, and averaged 10.0 cores. 77.3% were stereotactic biopsies, 13.6% ultrasound, and 6.8% MRI. 59.1% had excision after CNB. 82.1% of patients did not upstage. One patient upstaged to invasive ductal carcinoma (3.6%) and two patients to high-risk lesion (7.1%).

DISCUSSION: There was low upstage rate of RS/CSL on excisional biopsy. Centers could consider close surveillance for RS/CSL on CNB. Longer follow-up in cases of deferred excision is needed to ensure oncologic safety.}, } @article {pmid35261882, year = {2022}, author = {Sun, Y and Liang, S and Li, T and Peng, C and Yang, Y and Lin, Y and Ma, Y and Dong, C}, title = {Prognostic implications of combined high expression of CD47 and MCT1 in breast cancer: a retrospective study during a 10-year period.}, journal = {Translational cancer research}, volume = {11}, number = {1}, pages = {29-42}, pmid = {35261882}, issn = {2219-6803}, abstract = {BACKGROUND: Clinical outcome after surgery of breast cancer needs more prognostic markers to predict currently. Cluster of differentiation 47 (CD47), due to its overexpression in various tumors and ability to inhibit phagocytosis, has been identified as a new immune checkpoint. Monocarboxylate transporter 1 (MCT1) is a protein involved in the immunomodulatory activities of the tumor microenvironment (TME) by maintaining the pH through aerobic glycolysis.

METHODS: We explored the expression of CD47 and MCT1 in breast invasive ductal carcinoma specimens to determine their association with prognosis. A total of 137 breast invasive ductal carcinoma tissues were collected for CD47 and MCT1 immunohistochemical staining.

RESULTS: Statistically analyzed, our study first indicated that in both univariate and multivariate analyses, the coexpression of CD47 and MCT1 was an independent prognostic factor for a poor 10-year overall survival rate (10-OS) and 10-year progression-free survival rate (10-DFS) (P<0.05). In addition, the combined high expression of these two markers also led to worse OS and PFS rates in the TNM (II + III), histologic grade (I + II), HER2 overexpression and basal-like subgroups. High expression of CD47 and MCT1 and combined high expression of CD47 and MCT1 were associated with clinicopathological parameters, such as histological grade, TNM stage, death status, and recurrence status in breast cancer patients. However, in the multivariate survival analysis, high expression of CD47 alone was not an independent prognostic factor for the 10-OS or the 10-DFS (P=0.104; P=0.153), and high expression of MCT1 alone was not an independent predictor for a poor 10-DFS (P=0.177) either.

CONCLUSIONS: The coexpression of CD47 and MCT1 can serve as a prognostic biomarker leading to poor survival and an increased risk for recurrence, and this novel information could help guide the development of adjuvant therapy for breast cancer.}, } @article {pmid35260605, year = {2022}, author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and Young, K and Zein, RA and Baumert, A and Bilewicz, M and Bilgen, A and van Bezouw, MJ and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Paladino, MP and Petrović, N and Selvanathan, HP and Uluğ, ÖM and Wohl, MJ and Yeung, WLV and Burrows, B}, title = {Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3724}, pmid = {35260605}, issn = {2045-2322}, support = {2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; }, mesh = {Adult ; Aged ; Attitude ; COVID-19/*epidemiology/virology ; Canada ; Female ; Health Behavior ; Humans ; Indonesia ; Male ; Middle Aged ; *Politics ; Quarantine ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; *Trust ; United States/epidemiology ; }, abstract = {U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.}, } @article {pmid35252796, year = {2022}, author = {Mizusawa, H and Komatsu, A and Mimura, Y and Maejima, T}, title = {Development of male breast cancer in a patient with prostate cancer during androgen deprivation therapy.}, journal = {IJU case reports}, volume = {5}, number = {2}, pages = {118-121}, pmid = {35252796}, issn = {2577-171X}, abstract = {INTRODUCTION: Male breast cancer accounts for <1% of all breast cancer. We report a patient with prostate cancer during hormone therapy who developed breast cancer.

CASE PRESENTATION: An 88-year-old male underwent androgen deprivation therapy for prostate cancer and developed an induration in the left breast 7 years after the start of treatment. After close examination, he was diagnosed with left breast cancer with lymph node metastasis. The prostate cancer was stable in a hormone-sensitive state. Left mastectomy was performed and the pathological diagnosis was invasive ductal carcinoma.

DISCUSSION: In addition to our patient, seven patients who developed breast cancer during hormone therapy for prostate cancer were examined. Five of six patients had stage II or above, and four patients had lymph node metastases. Although local breast symptoms are frequently observed as adverse effects of hormone therapy, caution is warranted regarding male breast cancer.}, } @article {pmid35251981, year = {2022}, author = {Chi, Y and Shang, M and Xu, L and Gong, H and Tao, R and Song, L and Zhang, B and Yin, S and Cong, B and Li, H}, title = {Durable Effect of Pyrotinib and Metronomic Vinorelbine in HER2-Positive Breast Cancer With Leptomeningeal Disease: A Case Report and Literature Review.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {811919}, pmid = {35251981}, issn = {2234-943X}, abstract = {Leptomeningeal metastases (LM) are rare and catastrophic for metastatic breast cancer (MBC). The prognosis of HER2-positive breast cancer (BC) with LM is extremely poor. There is no high-quality evidence of treatment regimens in HER2-positive BC with LM yet. Here, we present a case of LM in a 50-year-old woman with HER2-positive BC. Immunohistochemistry revealed invasive ductal carcinoma, estrogen receptor negative, progesterone receptor negative, HER2 3+, P53 positive 80%, and Ki-67 positive 35%. Reported for the first time, the patient was given pyrotinib-targeted therapy (400 mg, oral, every day), metronomic vinorelbine (40 mg, oral, three times a week), and intrathecal methotrexate (10 mg, infrequent and irregular use due to poor compliance) synchronously. The patient received and benefited from the treatment regimen for 16 months. And the quality of life, as self-reported, improved significantly. We also comprehensively summarized all the case reports, observational studies, and clinical trials related to HER2-positive BC with LM in the PubMed database and ClinicalTrials.gov. Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa), intrathecal trastuzumab, whole-brain radiotherapy, and systemic therapy are commonly used treatment options according to a review of the literature and research. Pembrolizumab and trastuzumab deruxtecan (DS-8201) as novel drugs are promising in LM. Furthermore, trastuzumab emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs) such as tucatinib and neratinib have exhibited good efficacy in HER2-positive BC with central nervous system (CNS) metastases and deserve further exploration. In our report, combining pyrotinib-targeted therapy with metronomic chemotherapy is a potential regimen, which has presented satisfactory therapeutic efficacy and also warrants additional investigation in HER2-positive BC with LM.}, } @article {pmid35247977, year = {2022}, author = {Foster, GJ and Sievert, MAC and Button-Simons, K and Vendrely, KM and Romero-Severson, J and Ferdig, MT}, title = {Cyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {180}, pmid = {35247977}, issn = {1471-2164}, support = {P01 AI127338/AI/NIAID NIH HHS/United States ; P01 AI127338/NH/NIH HHS/United States ; }, mesh = {Animals ; *Antimalarials/pharmacology/therapeutic use ; Drug Resistance ; Genes, Developmental ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites/genetics ; Plasmodium falciparum ; Protozoan Proteins/genetics ; }, abstract = {BACKGROUND: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance. In lab-based studies, P. falciparum cultures are synchronized to remove this confounding factor, but the rapid detection of emerging resistance to artemisinin therapies requires rapid analysis of transcriptomes extracted directly from clinical samples. Here we propose the use of cyclical regression covariates (CRC) to eliminate the major confounding effect of developmentally driven transcriptional changes in clinical samples. We show that elimination of this confounding factor reduces both Type I and Type II errors and demonstrate the effectiveness of this approach using a published dataset of 1043 transcriptomes extracted directly from patient blood samples with different patient clearance times after treatment with artemisinin.

RESULTS: We apply this method to two publicly available datasets and demonstrate its ability to reduce the confounding of differences in transcript levels due to misaligned intraerythrocytic development time. Adjusting the clinical 1043 transcriptomes dataset with CRC results in detection of fewer functional categories than previously reported from the same data set adjusted using other methods. We also detect mostly the same functional categories, but observe fewer genes within these categories. Finally, the CRC method identifies genes in a functional category that was absent from the results when the dataset was adjusted using other methods. Analysis of differential gene expression in the clinical data samples that vary broadly for developmental stage resulted in the detection of far fewer transcripts in fewer functional categories while, at the same time, identifying genes in two functional categories not present in the unadjusted data analysis. These differences are consistent with the expectation that CRC reduces both false positives and false negatives with the largest effect on datasets from samples with greater variance in developmental stage.

CONCLUSIONS: Cyclical regression covariates have immediate application to parasite transcriptome sequencing directly from clinical blood samples and to cost-constrained in vitro experiments.}, } @article {pmid35245349, year = {2022}, author = {Hophan, SL and Odnokoz, O and Liu, H and Luo, Y and Khan, S and Gradishar, W and Zhou, Z and Badve, S and Torres, MA and Wan, Y}, title = {Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management.}, journal = {Endocrinology}, volume = {163}, number = {4}, pages = {}, pmid = {35245349}, issn = {1945-7170}, support = {R01 CA245699/CA/NCI NIH HHS/United States ; UG3 CA256967/CA/NCI NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Breast ; *Breast Neoplasms/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/therapy ; Female ; Humans ; }, abstract = {Ductal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.}, } @article {pmid35239627, year = {2021}, author = {Choi, B}, title = {Comparison of Ultrasound Features With Maximum Standardized Uptake Value Assessed by 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Prognosis of Estrogen Receptor+/Human Epithelial Growth Factor Receptor 2- Breast Cancer.}, journal = {Ultrasound quarterly}, volume = {38}, number = {1}, pages = {18-24}, pmid = {35239627}, issn = {1536-0253}, mesh = {*Breast Neoplasms/diagnostic imaging ; Estrogen Receptor beta ; Female ; *Fluorodeoxyglucose F18/metabolism ; Humans ; Positron Emission Tomography Computed Tomography/methods ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Growth Factor ; Retrospective Studies ; }, abstract = {estrogen receptor (ER)+/human epithelial growth factor receptor 2 (HER2)- breast cancers have less aggressive traits and a favorable prognosis when treated early. Prediction of prognosis for treatment outcome or survival in ER+/HER2- cancer is important. Ultrasound (US) is an effective and easy technique for breast cancer diagnosis and tumor characterization. Positron emission tomography/computed tomography (PET/CT) is widely used for diagnosis, staging, and therapeutic response in cancer evaluation, and a high maximum standardized uptake value (SUVmax) is associated with poor prognosis. The study aim was to compare the prognostic value of US features with that of the SUVmax assessed by PET/CT in ER+/HER- breast cancer patients. We retrospectively identified breast cancer patients in our institutional database who had undergone preoperative US and PET/CT, and 96 patients with invasive ductal carcinoma and ductal carcinoma in situ were included in this study. The US features of mass shape, margin, echo pattern, orientation, posterior features, boundary, and calcification in the mass were analyzed. We then analyzed the US features to look for correlations with SUVmax and associations with margins, boundaries, posterior features, histological grade, and ki-67 expression. High SUVmax was correlated with irregular shape, not-circumscribed margin, posterior acoustic enhancement, echogenic halo, and calcification in the mass (P < 0.05, all). Posterior acoustic enhancement was correlated with high ki-67 expression. Many US features of ER+/HER- breast cancer showed associations with SUVmax. Some US features of ER+/HER- breast cancer were useful for predicting prognosis.}, } @article {pmid35238350, year = {2023}, author = {Egea, V and Megens, RTA and Santovito, D and Wantha, S and Brandl, R and Siess, W and Khani, S and Soehnlein, O and Bartelt, A and Weber, C and Ries, C}, title = {Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques.}, journal = {Cardiovascular research}, volume = {119}, number = {1}, pages = {155-166}, pmid = {35238350}, issn = {1755-3245}, mesh = {Mice ; Animals ; Humans ; *MicroRNAs/genetics ; *Plaque, Atherosclerotic ; *Atherosclerosis/genetics ; Cytokines ; Immunologic Factors ; *Mesenchymal Stem Cells ; }, abstract = {AIMS: Atherosclerosis is a chronic inflammatory disease of the arteries leading to the formation of atheromatous plaques. Human mesenchymal stem cells (hMSCs) are recruited from the circulation into plaques where in response to their environment they adopt a phenotype with immunomodulatory properties. However, the mechanisms underlying hMSC function in these processes are unclear. Recently, we described that miRNA let-7f controls hMSC invasion guided by inflammatory cytokines and chemokines. Here, we investigated the role of let-7f in hMSC tropism to human atheromas and the effects of the plaque microenvironment on cell fate and release of soluble factors.

METHODS AND RESULTS: Incubation of hMSCs with LL-37, an antimicrobial peptide abundantly found in plaques, increased biosynthesis of let-7f and N-formyl peptide receptor 2 (FPR2), enabling chemotactic invasion of the cells towards LL-37, as determined by qRT-PCR, flow cytometry, and cell invasion assay analysis. In an Apoe-/- mouse model of atherosclerosis, circulating hMSCs preferentially adhered to athero-prone endothelium. This property was facilitated by elevated levels of let-7f in the hMSCs, as assayed by ex vivo artery perfusion and two-photon laser scanning microscopy. Exposure of hMSCs to homogenized human atheromatous plaque material considerably induced the production of various cytokines, chemokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinases, as studied by PCR array and western blot analysis. Moreover, exposure to human plaque extracts elicited differentiation of hMSCs into cells of the myogenic lineage, suggesting a potentially plaque-stabilizing effect.

CONCLUSIONS: Our findings indicate that let-7f promotes hMSC tropism towards atheromas through the LL-37/FPR2 axis and demonstrate that hMSCs upon contact with human plaque environment develop a potentially athero-protective signature impacting the pathophysiology of atherosclerosis.}, } @article {pmid35231053, year = {2022}, author = {Troughton, LD and O'Loughlin, DA and Zech, T and Hamill, KJ}, title = {Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0264430}, pmid = {35231053}, issn = {1932-6203}, support = {BB/L020513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P0257731/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Immunohistochemistry ; Laminin/genetics/metabolism ; Neoplasm Invasiveness ; }, abstract = {Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.}, } @article {pmid35229941, year = {2022}, author = {Naim-Feil, J and Fitzgerald, PB and Rubinson, M and Lubman, DI and Sheppard, DM and Bradshaw, JL and Levit-Binnun, N and Moses, E}, title = {Anomalies in global network connectivity associated with early recovery from alcohol dependence: A network transcranial magnetic stimulation and electroencephalography study.}, journal = {Addiction biology}, volume = {27}, number = {2}, pages = {e13146}, pmid = {35229941}, issn = {1369-1600}, mesh = {*Alcoholism ; Brain Mapping ; Electroencephalography ; Humans ; Prefrontal Cortex/diagnostic imaging/physiology ; Transcranial Magnetic Stimulation ; }, abstract = {Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery.}, } @article {pmid35225800, year = {2022}, author = {Menezes, ACS and Alves, LDB and Heimlich, FV and Fonseca, RCSP and Antunes, HS and Pereira, DL}, title = {Adenocarcinoma of mammary origin in the maxillary gingiva: a case report and brief literature review.}, journal = {General dentistry}, volume = {70}, number = {2}, pages = {28-32}, pmid = {35225800}, issn = {0363-6771}, mesh = {*Adenocarcinoma/pathology ; Aged ; *Breast Neoplasms/diagnosis/pathology ; Female ; Gingiva/pathology ; Humans ; }, abstract = {Maxillofacial metastases are rare but represent advanced disease progression and a poor prognosis. The primary purpose of this article is to describe a patient with previously diagnosed and treated invasive ductal breast carcinoma who developed a metastatic lesion in the maxillary gingiva. In addition, this article presents a brief literature review of case reports on metastatic breast cancer manifestations in the gingiva. In the present case, a 68-year-old woman had been diagnosed and treated for invasive ductal breast carcinoma. At the 6-month follow-up after treatment for breast cancer, she complained of pain in the right leg and spine, swelling in the right arm associated with redness, and a nodular growth in the maxillary gingiva that was painful, friable, and associated with tooth mobility. Imaging examinations and microscopic analysis of an oral biopsy specimen revealed disease progression to the oral cavity, femur, lung, and brain. Because of the advanced disease, the patient died within a few weeks. The literature review identified 6 articles that reported varied clinical presentations of metastatic breast cancer in the gingiva. Invasive ductal carcinoma was the most common histologic type. Routine dental follow-up of patients with cancer is essential for the identification and diagnosis of oral lesions to ensure early intervention for lesions that may be distant metastases mimicking benign lesions.}, } @article {pmid35225058, year = {2022}, author = {Alhesa, A and Awad, H and Bloukh, S and Al-Balas, M and El-Sadoni, M and Qattan, D and Azab, B and Saleh, T}, title = {PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy.}, journal = {International journal of immunopathology and pharmacology}, volume = {36}, number = {}, pages = {3946320221078433}, pmid = {35225058}, issn = {2058-7384}, mesh = {*B7-H1 Antigen/metabolism ; Biomarkers, Tumor/metabolism ; *Carcinoma, Ductal ; Humans ; Neoadjuvant Therapy ; }, abstract = {OBJECTIVES: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC).

METHODS: PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients (n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples (n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off.

RESULTS: In the post-operative, post-NAC samples (n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar's, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples (p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status (p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate (p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples (t = 0.581, p = 0.563 or Wilcoxon's Signed Rank test; z = -0.625, p = 0.529).

CONCLUSION: Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.}, } @article {pmid35222844, year = {2022}, author = {Fenollar, À and Ros-Lucas, A and Pía Alberione, M and Martínez-Peinado, N and Ramírez, M and Ángel Rosales-Motos, M and Y Lee, L and Alonso-Padilla, J and Izquierdo, L}, title = {Compounds targeting GPI biosynthesis or N-glycosylation are active against Plasmodium falciparum.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {850-863}, pmid = {35222844}, issn = {2001-0370}, abstract = {The emergence of resistance to first-line antimalarials, including artemisinin, the last effective malaria therapy in some regions, stresses the urgent need to develop new effective treatments against this disease. The identification and validation of metabolic pathways that could be targeted for drug development may strongly contribute to accelerate this process. In this study, we use fully characterized specific inhibitors targeting glycan biosynthetic pathways as research tools to analyze their effects on the growth of the malaria parasite Plasmodium falciparum and to validate these metabolic routes as feasible chemotherapeutic targets. Through docking simulations using models predicted by AlphaFold, we also shed new light into the modes of action of some of these inhibitors. Molecules inhibiting N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase (GlcNAc-PI de-N-acetylase, PIGL/GPI12) or the inositol acyltransferase (GWT1), central for glycosylphosphatidylinositol (GPI) biosynthesis, halt the growth of intraerythrocytic asexual parasites during the trophozoite stages of the intraerythrocytic developmental cycle (IDC). Remarkably, the nucleoside antibiotic tunicamycin, which targets UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (ALG7) and N-glycosylation in other organisms, induces a delayed-death effect and inhibits parasite growth during the second IDC after treatment. Our data indicate that tunicamycin induces a specific inhibitory effect, hinting to a more substantial role of the N-glycosylation pathway in P. falciparum intraerythrocytic asexual stages than previously thought. To sum up, our results place GPI biosynthesis and N-glycosylation pathways as metabolic routes with potential to yield much-needed therapeutic targets against the parasite.}, } @article {pmid35220223, year = {2022}, author = {Dantas, FT and Felix-Silva, PH and Angotti-Carrara, HH and Dos-Reis, FJC and Junior, MT and DE-Souza, SLS and Palioto, DB}, title = {A New Method for Obtaining Tumor Interstitial Fluid Applied to Cytokine Analysis of Breast Carcinoma Samples.}, journal = {Anticancer research}, volume = {42}, number = {3}, pages = {1327-1332}, doi = {10.21873/anticanres.15600}, pmid = {35220223}, issn = {1791-7530}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Large-Core Needle ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/*immunology ; Female ; Humans ; Interleukin-1beta/*analysis ; Middle Aged ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: Tumor interstitial fluid (TIF), a component of the tumor microenvironment, is a valuable source of molecules and substances that help in diagnosis and prognosis of solid tumors. There is still no consensus on the optimal method for collecting TIF. Therefore, this study aimed to evaluate the effectiveness of a new method of collecting TIF in invasive ductal carcinoma (IDC) samples for cytokine interleukin 1β (IL1β) quantification.

MATERIALS AND METHODS: Forty women allowed the collection of TIF using absorbent paper strips during the performance of the core biopsy. The samples were stored at a temperature of -80°C and then analyzed using an enzyme-linked immunoassay.

RESULTS: The mean values for IL1β and total protein were 11.39 mg/ml and 2.15 mg/ml, respectively.

CONCLUSION: it was possible to quantify the cytokine IL1β and the total protein concentration present in the tumor tissue through TIF collection with the use of absorbent paper filters, demonstrating the effectiveness of this new method in oncology.}, } @article {pmid35220107, year = {2022}, author = {Aggius-Vella, E and Gori, M and Campus, C and Moore, BCJ and Pardhan, S and Kolarik, AJ and Van der Stoep, N}, title = {Auditory distance perception in front and rear space.}, journal = {Hearing research}, volume = {417}, number = {}, pages = {108468}, doi = {10.1016/j.heares.2022.108468}, pmid = {35220107}, issn = {1878-5891}, mesh = {Acoustic Stimulation ; Auditory Perception ; Cues ; *Distance Perception ; Humans ; Sound ; *Sound Localization ; Space Perception ; }, abstract = {The distance of sound sources relative to the body can be estimated using acoustic level and direct-to-reverberant ratio cues. However, the ability to do this may differ for sounds that are in front compared to behind the listener. One reason for this is that vision, which plays an important role in calibrating auditory distance cues early in life, is unavailable for rear space. Furthermore, the filtering of sounds by the pinnae differs if they originate from the front compared to the back. We investigated auditory distance discrimination in front and rear space by comparing performance for auditory spatial bisection of distance and minimum audible distance discrimination (MADD) tasks. In the bisection task, participants heard three successive bursts of noise at three different distances and indicated whether the second sound (probe) was closer in space to the first or third sound (references). In the MADD task, participants reported which of two successive sounds was closer. An analysis of variance with factors task and region of space showed worse performance for rear than for front space, but no significant interaction between task and region of space. For the bisection task, the point of subjective equality (PSE) was slightly biased towards the body, but the absolute magnitude of the PSE did not differ between front and rear space. These results are consistent with the hypothesis that visual information is important in calibrating the auditory representation of front space in distance early in life.}, } @article {pmid35210951, year = {2021}, author = {Halilbasic, E and Iljazovic, E and Mehmedovic, Z and Brkic, E and Sarkanovic, G}, title = {Methylene Blue as Inexpensive and Reliable Sole Sentinel Lymph Node Mapping Agent for Patients with Invasive Ductal Carcinoma.}, journal = {Materia socio-medica}, volume = {33}, number = {4}, pages = {282-287}, pmid = {35210951}, issn = {1512-7680}, abstract = {BACKGROUND: Invasive ductal cancer (IDC) represents about 75% of all breast malignancies. There are many breast cancer prognostic factors, but the ones that have the most impact on the survival rates in advanced breast cancer are tumor size and regional lymph node involvement. Axillary lymph node dissection (ALND) has particularly important and undoubtful role in current surgical options for breast cancer treatment. With the introduction of sentinel lymph node biopsy (SLNB) for breast cancer patients it was possible to identify those to whom regional spread of the disease did not occur at the time of surgery, and thus spare them an unnecessary ALND procedure.

OBJECTIVE: To determine the rate of sentinel lymph node (SLN) detection using only methylene blue dye as a mapping agent, as well as to correlate the number of positive SLNs with the number of positive non-sentinel lymph nodes (non-SLNs).

METHODS: The study represents a prospective study that included 50 female patients with histologically confirmed invasive ductal carcinoma (IDC) who underwent SLNB using only methylene blue dye as the mapping agent, while the detection and harvest of SNL was done by visual control only. All patients also underwent an obligatory complete ALND, which was as that time the institutional oncological protocol for surgical treatment of histologically confirmed IDC. The final data such as tumor size, SLN and non-SLN status were obtained by further analysis of pathohistological reports from tumor biopsy and other surgical specimens.

RESULTS: The accuracy rate of SLN detection was 98%. The number of detected SLN was in the range of 1 to 6, with an average of 2 for each patient. The number of positive SLN was in significant correlation with the number of tumor-affected non-SNL (p<0,001). Further analysis showed that for each increase in the number of positive SLN by 1, the risk of positive non-SLN increased 6-fold, OR=6,22 (p<0,001).

CONCLUSION: Use of methylene blue dye as a sole mapping agent when performing SLNB in patients with IDC is a reliable and effective method that can be safely implemented in medical institutions that lack availability of nuclear medicine services or significant monetary funds.}, } @article {pmid35210861, year = {2022}, author = {Han, B and Gu, Z and Liu, Z and Ling, H}, title = {Clinical Characteristics and Survival Outcomes of Infiltrating Lobular Carcinoma: A Retrospective Study of 365 Cases in China.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {647-658}, pmid = {35210861}, issn = {1179-1322}, abstract = {PURPOSE: The objective of this study was to compare the demographic characteristics, clinicopathological factors and survival outcomes between infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) using our single-center database.

METHODS: Seventeen thousand two hundred and three breast cancer patients were treated at Fudan University Shanghai Cancer Center (FUSCC) from January 2000 to December 2017. We identified 365 cases with ILC and 16,838 cases with IDC. The Pearson chi-square test was used to compare tumor characteristics, and the Kaplan-Meier methods were used to perform the survival analysis.

RESULTS: ILC had some distinctive characteristics from IDC such as older age (ranged from 61 to 80: ILC 26.8% vs IDC 19.9%, P < 0.001; over 80: ILC 1.6% vs IDC 0.8%, P < 0.001), larger tumor size (ranged from 2 to 5: ILC 45.2% vs IDC 37.1%, P = 0.011), much more hormone receptor expression (ILC 92.9% vs IDC 73.0%, P < 0.001), extremely less HER-2 expression (ILC 7.1% vs IDC 25.9%, P < 0.001). The overall survival and disease-free survival of ILC were worse than IDC (5-year OS, ILC 93.6% vs IDC 94.5%, P < 0.001; 5-year DFS, ILC 88.5% vs IDC 91.6%, P = 0.008). It was worth noting that the ILC patients had a worse overall survival than IDC patients after our propensity score matching study (P = 0.037). The univariate analysis concluded that positive HR (hormone receptor), high expression of Ki-67 and higher pathologic tumor stage were poor prognostic markers of ILC. Multivariate analysis demonstrated that tumor stage was a poor prognostic marker after adjustment for the effects of the above three factors. The most common primary site of metastasis was bone, but the proportion in the ILC group was much higher than that in the IDC group (56.25% vs 36.40%, P = 0.003).

CONCLUSION: Compared with IDC, ILC survived worse and was more prone to bone metastasis. Therefore, a comprehensive understanding of ILC and specific treatments are needed for further research.}, } @article {pmid35207775, year = {2022}, author = {Huang, CC and Chang, CL and Sun, M and Chiang, MF and Sum, SY and Zhang, J and Wu, SY}, title = {Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {12}, number = {2}, pages = {}, pmid = {35207775}, issn = {2075-4426}, abstract = {This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.}, } @article {pmid35206957, year = {2022}, author = {Gouda, W and Almurafeh, M and Humayun, M and Jhanjhi, NZ}, title = {Detection of COVID-19 Based on Chest X-rays Using Deep Learning.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {35206957}, issn = {2227-9032}, support = {DSR-2021-02-0370//Al Jouf University/ ; }, abstract = {The coronavirus disease (COVID-19) is rapidly spreading around the world. Early diagnosis and isolation of COVID-19 patients has proven crucial in slowing the disease's spread. One of the best options for detecting COVID-19 reliably and easily is to use deep learning (DL) strategies. Two different DL approaches based on a pertained neural network model (ResNet-50) for COVID-19 detection using chest X-ray (CXR) images are proposed in this study. Augmenting, enhancing, normalizing, and resizing CXR images to a fixed size are all part of the preprocessing stage. This research proposes a DL method for classifying CXR images based on an ensemble employing multiple runs of a modified version of the Resnet-50. The proposed system is evaluated against two publicly available benchmark datasets that are frequently used by several researchers: COVID-19 Image Data Collection (IDC) and CXR Images (Pneumonia). The proposed system validates its dominance over existing methods such as VGG or Densnet, with values exceeding 99.63% in many metrics, such as accuracy, precision, recall, F1-score, and Area under the curve (AUC), based on the performance results obtained.}, } @article {pmid35205651, year = {2022}, author = {Gómez-Cuadrado, L and Bullock, E and Mabruk, Z and Zhao, H and Souleimanova, M and Noer, PR and Turnbull, AK and Oxvig, C and Bertos, N and Byron, A and Dixon, JM and Park, M and Haider, S and Natrajan, R and Sims, AH and Brunton, VG}, title = {Characterisation of the Stromal Microenvironment in Lobular Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {4}, pages = {}, pmid = {35205651}, issn = {2072-6694}, support = {C157/A23219/CRUK_/Cancer Research UK/United Kingdom ; C157/A29279/CRUK_/Cancer Research UK/United Kingdom ; 734/2018/878//Endeavour Scholarship/ ; NA/BBC_/Breast Cancer Now/United Kingdom ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways.}, } @article {pmid35204438, year = {2022}, author = {Huang, PC and Wu, RC and Juan, YH and Ho, HY and Lin, YC and Huang, YT and Ng, SH and Lai, CH and Chao, A and Lin, G}, title = {Diagnostic Accuracy of Whole-Body Computed Tomography for Incidental Ovarian Tumors in Patients with Prior Breast Cancer.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35204438}, issn = {2075-4418}, support = {CLRPG3K0021//Chang Gung Medical Foundation/ ; CLRPG3K0022//Chang Gung Medical Foundation/ ; MOST 110-2628-B-182A-018//Ministry of Science and Technology (Taiwan)/ ; }, abstract = {Whole-body computed tomography (WBCT) serves as the first-line imaging modality for breast cancer follow-up. To investigate the imaging characteristics and diagnostic accuracy of WBCT for incidental ovarian tumors in patients with prior breast cancer, we retrospectively reviewed a consecutive cohort of 13,845 patients with breast cancer, of whom 149 had pathologically-proven ovarian lesions. We excluded patients with ovarian diagnosis before breast cancer, CT scan not including ovary, CT-pathology interval >30 days, and severe CT artifact. Among our 60 breast cancer patients (median age, 46 years) with pathologically proven ovarian lesions, 49 patients had benign diseases, seven had primary ovarian cancer and four had ovarian metastasis from breast cancer. The histologic types of breast cancer with ovarian metastases included invasive ductal carcinoma, lobular carcinoma and angiosarcoma. Cystic ovarian lesions identified on WBCT during the breast cancer follow-up are more likely to be benign, while solid-cystic lesions are likely to be primary ovarian cancers, and solid lesions may indicate ovarian metastasis. The diagnostic accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve of WBCT were 98.3%, 100.0%, 98.0%, and 0.99 (malignant vs. benign); 90.0%, 100.0%, 85.7%, and 0.93 (metastasis vs. primary ovarian cancer), respectively. The only false positive solid lesion was a Sertoli-Leydig tumor. In conclusion, WBCT may help diagnose incidental ovarian tumors in patients with prior breast cancers and guide disease management.}, } @article {pmid35200056, year = {2022}, author = {Hannarici, Z and Yılmaz, A and Buyukbayram, ME and Turhan, A and Tekin, SB and Bilici, M}, title = {Lipegfilgrastim may cause hyperleukocytosis.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {28}, number = {8}, pages = {1902-1905}, doi = {10.1177/10781552221082645}, pmid = {35200056}, issn = {1477-092X}, mesh = {Humans ; Female ; Middle Aged ; Filgrastim/therapeutic use ; *Allopurinol ; *Uric Acid ; Polyethylene Glycols ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Pain/chemically induced ; }, abstract = {INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.

CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.

MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.

DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.}, } @article {pmid35199786, year = {2021}, author = {Neupane, S and Dhakal, S and Walawalakar, S and Parajuli, SB and Sapkota, S}, title = {Bilateral Neuroendocrine Carcinoma of Breast: A Case Report.}, journal = {JNMA; journal of the Nepal Medical Association}, volume = {59}, number = {244}, pages = {1320-1322}, pmid = {35199786}, issn = {1815-672X}, mesh = {Breast/pathology ; *Breast Neoplasms/diagnosis ; *Carcinoma, Neuroendocrine/diagnosis/drug therapy/surgery ; Diagnosis, Differential ; Female ; Humans ; Mastectomy ; }, abstract = {Primary neuroendocrine carcinomas of the breast are rare of all breast carcinomas. They may be welldifferentiated, poorly differentiated, or invasive breast cancers with neuroendocrine differentiation. They are staged and treated similarly to conventional breast cancer. Herein, we report a case of invasive ductal carcinoma with neuroendocrine differentiation of the breast in a 73 years female with a history of breast lump initially in the lower inner quadrant of left breast and a month later, similar lump at the same site in right breast. Patient underwent Modified Radical Mastectomy bilaterally followed by adjuvant chemotherapy based on Carboplatin and Etoposide regimen.}, } @article {pmid35193807, year = {2022}, author = {Haque, W and Verma, V and Schwartz, MR and Lim, B and Mangalampalli, N and Butler, EB and Teh, BS}, title = {Neoadjuvant Chemotherapy for Metaplastic Breast Cancer: Response Rates, Management, and Outcomes.}, journal = {Clinical breast cancer}, volume = {22}, number = {5}, pages = {e691-e699}, doi = {10.1016/j.clbc.2022.01.006}, pmid = {35193807}, issn = {1938-0666}, mesh = {Breast/pathology ; *Breast Neoplasms/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Staging ; }, abstract = {INTRODUCTION: Neoadjuvant chemotherapy (NAC) for breast cance has not been well studied for metaplastic breast cancer (MBC), a rare but aggressive type of breast cancer.

MATERIALS AND METHODS: The National Cancer Database was queried (2004-2017) for females with cM0 MBC who received NAC and definitive surgery with a pathologic staging record. Statistics included Kaplan-Meier overall survival (OS) analysis, multivariable logistic regression, and Cox proportional hazards modeling.

RESULTS: Of 903 MBC patients, 88 (9.8%) experienced a pathologic complete response (pCR). The vast majority of ypT0 cases were initially cT1-2. On multivariable logistic regression, cT1 disease was a single factor that was associated with pCR. The majority of patients with MBC undergoing pCR still underwent mastectomy (62.5%) and sentinel node biopsy (67.1%). Axillary dissection was more common in non-pCR cases (49.3% vs. 29.6%, P = .001). The 5 year OS difference amongst MBC patients between pCR vs. RCB1-3 was significant (93 vs. 63%, P < .001). There was no difference observed between MpBC with pCR and non-MpBC invasive ductal carcinoma (IDC) with pCR (93 vs. 93%), with pCR (P > .05 for all molecular subtypes).

CONCLUSION: This study confirms that response rates of MBC to NAC are low, with pCR being relatively infrequent. However, early-stage MBC may be more likely to achieve pCR. These findings combined with emerging research on identifying favorable histopathologic subtypes of MBC may better elucidate subsets with higher proclivity for pCR, especially because these patients achieve satisfactory survival, comparable to that of IDC with pCR.}, } @article {pmid35187122, year = {2022}, author = {Neves, EGA and Koh, CC and Souza-Silva, TG and Passos, LSA and Silva, ACC and Velikkakam, T and Villani, F and Coelho, JS and Brodskyn, CI and Teixeira, A and Gollob, KJ and Nunes, MDCP and Dutra, WO}, title = {T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {787423}, pmid = {35187122}, issn = {2297-055X}, abstract = {Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4[+], CD8[+], and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8[+] T-cells were highly activated in CCC as compared to IDC, CD4[+] T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.}, } @article {pmid35186753, year = {2022}, author = {Mao, C and Jiang, W and Huang, J and Wang, M and Yan, X and Yang, Z and Wang, D and Zhang, X and Shen, J}, title = {Quantitative Parameters of Diffusion Spectrum Imaging: HER2 Status Prediction in Patients With Breast Cancer.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {817070}, pmid = {35186753}, issn = {2234-943X}, abstract = {OBJECTIVE: To explore the value of quantitative parameters derived from diffusion spectrum imaging (DSI) in preoperatively predicting human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer.

METHODS: In this prospective study, 114 and 56 female patients with invasive ductal carcinoma were consecutively included in a derivation cohort and an independent validation cohort, respectively. Each patient was categorized into HER2-positive or HER2-negative groups based on the pathologic result. All patients underwent DSI and conventional MRI including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI). The tumor size, type of the time-signal intensity curve (TIC) from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, and quantitative parameters derived from DSI, including diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) of primary tumors, were measured and compared between the HER2-positive and HER2-negative groups in the derivation cohort. Univariable and multivariable logistic regression analyses were used to determine the potential independent predictors of HER2 status. The discriminative ability of quantitative parameters was assessed by receiver operating characteristic (ROC) curve analyses and validated in the independent cohort.

RESULTS: In the derivation cohort, the tumor size, TIC type, and ADC values did not differ between the HER2-positive and HER2-negative groups (p = 0.126-0.961). DSI quantitative parameters including axial kurtosis of DKI (DKI_AK), non-Gaussianity (MAP_NG), axial non-Gaussianity (MAP_NGAx), radial non-Gaussianity (MAP_NGRad), return-to-origin probability (MAP_RTOP), return-to-axis probability of MAP (MAP_RTAP), and intracellular volume fraction of NODDI (NODDI_ICVF) were lower in the HER2-positive group than in the HER2-negative group (p ≤ 0.001-0.035). DSI quantitative parameters including radial diffusivity (DTI_RD), mean diffusivity of DTI (DTI_MD), mean squared diffusion (MAP_MSD), and q-space inverse variance of MAP (MAP_QIV) were higher in the HER2-positive group than in the HER2-negative group (p = 0.016-0.049). The ROC analysis showed that the area under the curve (AUC) of ADC was 0.632 and 0.568, respectively, in the derivation and validation cohorts. The AUC values of DSI quantitative parameters ranged from 0.628 to 0.700 and from 0.673 to 0.721, respectively, in the derivation and validation cohorts. Logistic regression analysis showed that only NODDI_ICVF was an independent predictor of HER2 status (p = 0.001), with an AUC of 0.700 and 0.721, respectively, in the derivation and validation cohorts.

CONCLUSIONS: DSI could be helpful for preoperative prediction of HER2, but DSI alone may not be sufficient in predicting HER2 status preoperatively in patients with breast cancer.}, } @article {pmid35181468, year = {2022}, author = {Russell, AE and Liao, Z and Tkach, M and Tarwater, PM and Ostrowski, M and Théry, C and Witwer, KW}, title = {Cigarette smoke-induced extracellular vesicles from dendritic cells alter T-cell activation and HIV replication.}, journal = {Toxicology letters}, volume = {360}, number = {}, pages = {33-43}, pmid = {35181468}, issn = {1879-3169}, support = {R01 AI144997/AI/NIAID NIH HHS/United States ; R01 DA040385/DA/NIDA NIH HHS/United States ; R01 DA047807/DA/NIDA NIH HHS/United States ; T32 AG052375/AG/NIA NIH HHS/United States ; }, mesh = {*Cigarette Smoking ; Dendritic Cells ; *Extracellular Vesicles/metabolism ; Lymphocyte Activation ; Virus Replication ; }, abstract = {Despite decreased rates of tobacco smoking in many areas, cigarette smoking remains a major contributor to many health problems. Cigarette smoking can reduce immune system functioning while concurrently increasing inflammation. Dendritic cells in the lung exposed to cigarette smoke become stimulated and go on to activate T-cells. Extracellular vesicles (EVs) are nano-sized particles released by cells. They participate in intercellular communication by transferring functional proteins and nucleic acids to recipient cells and have been implicated in immune responses. For example, they can display MHC-peptide complexes to activate T-cells. In the current study, we sought to understand the role of cigarette smoke extract (CSE) on dendritic cell-derived EVs and their capacity to activate and differentiate T-cells. Primary human dendritic cells (iDCs) were exposed to CSE and EVs were separated and characterized. We exposed autologous primary CD4 + T-cells to iDC-EVs and observed T helper cell populations skewing towards Th1 and Th17 phenotypes. As HIV + individuals are disproportionately likely to be current smokers, we also examined the effects of iDC-EVs on acutely infected T-cells as well as on a cell model of HIV latency (ACH-2). We found that in most cases, iDC-CSE EVs tended to reduce p24 release from the acutely infected primary T-cells, albeit with great variability. We did not observe large effects of iDC-EVs or direct CSE exposure on p24 release from the ACH-2 cell line. Together, these data suggest that iDC-CSE EVs have the capacity to modulate the immune responses, in part by pushing T-cells towards Th1 and Th17 phenotypes.}, } @article {pmid35180758, year = {2022}, author = {Parmeshwar, N and Song, S and Alcon, A and Kim, EA}, title = {The Incidence of Breast Cancer After Gender-Affirming Mastectomy in Transmen.}, journal = {Annals of plastic surgery}, volume = {88}, number = {4 Suppl 4}, pages = {S332-S336}, doi = {10.1097/SAP.0000000000003083}, pmid = {35180758}, issn = {1536-3708}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/surgery/pathology ; Mastectomy ; Receptors, Progesterone ; Receptors, Estrogen ; Incidence ; Hormones ; }, abstract = {BACKGROUND: The incidence of breast cancer in transmale patients and their continued risk after gender-affirming mastectomy (GAM) has not been well established. Plastic surgeons who offer GAM are often one of the few medical professionals sought out by this population, placing them in a unique position to not only deliver surgical care but also improve access to preventative cancer care.

METHODS: We reviewed the senior author's experience with GAMs over the past 5 years for any incidence of breast cancer noted after or at time of surgery. We subsequently performed a thorough review of the literature for cases of breast cancer in transmen, to provide a comprehensive overview of screening, therapy, and postoperative surveillance practices.

RESULTS: We identified 2 cases of breast cancer (ages 49 and 54 years) found on routine examination of pathology specimens after GAM at our institution. Both patients had been taking hormone therapy for the past 1 year. Pathology specimen revealed low-grade estrogen receptor-/progesterone receptor-positive ductal carcinoma in situ in 1 patient, and estrogen receptor-/progesterone receptor-positive invasive ductal carcinoma in the other. Both patients were referred to oncology for appropriate treatment, and both elected to continue their exogenous hormone therapy for personal reasons.Review of the literature demonstrated 36 other cases of documented breast cancer in transmen. Sixty-seven percent (24) were found after GAM, and of those, 50% were incidentally found on pathology specimen. At least 50% were found to be either estrogen-, progesterone-, or androgen receptor-positive cancers. At least 17% of cases documented continued use of masculinizing hormone therapy after cancer diagnosis.

CONCLUSIONS: Most documented cases of breast cancer in transmen were diagnosed after gender-affirming surgery, which would suggest residual breast tissue does pose some risk for breast cancer. In addition, those diagnosed with cancer may elect to continue exogenous testosterone therapy despite potential added risks with hormone-receptor positivity. These cases highlight the need for agreement in current screening practices, surgical recommendations, and continuation of masculinizing hormone therapy.Plastic surgeons have the unique opportunity to educate these patients on appropriate breast cancer-related surveillance both before and after chest surgery.}, } @article {pmid35180589, year = {2022}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Contralateral axillary lymph node metastasis in primary breast cancer: A case report.}, journal = {International journal of surgery case reports}, volume = {92}, number = {}, pages = {106810}, pmid = {35180589}, issn = {2210-2612}, abstract = {INTRODUCTION: Contralateral axillary lymph node metastasis (CAM) is rare, especially in primary breast cancer.

PRESENTATION OF CASE: A 71-year-old woman visited our hospital after noticing a mass in her right breast. A mass of 5 cm in diameter with skin infiltration was palpable on the medial side of the right breast. She underwent a needle biopsy and was diagnosed with invasive ductal carcinoma. On various imaging modalities, there were no distant metastases but bilateral axillary lymph node metastases were found. She underwent preoperative chemotherapy and showed a clinical partial response. After thorough discussion, she opted for surgery and underwent partial mastectomy of the right breast and bilateral axillary lymph node dissection. Histopathological examination revealed residual breast tumor and one metastatic axillary lymph node on each side. Postoperative radiotherapy and hormone therapy were performed. The patient is alive and recurrence-free as of 1 year after the start of treatment.

CONCLUSION: CAM is often regarded as distant metastasis, but can be considered curable if there is no distant metastasis to other organs. CAM without distant metastasis to other organs should be treated with curative intent in order to avoid a disadvantage to the patient.}, } @article {pmid35178446, year = {2022}, author = {Li, X and Zhao, G and Mi, X and Xu, T and Li, X and Liu, B}, title = {Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {3321409}, pmid = {35178446}, issn = {2314-6141}, mesh = {*Breast Neoplasms/drug therapy/genetics ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; Glucose Transporter Type 3/genetics ; Humans ; *LIM Domain Proteins/genetics ; Survivin/genetics ; TEA Domain Transcription Factors/genetics ; }, abstract = {The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.}, } @article {pmid35176614, year = {2022}, author = {Dalenc, F and Lusque, A and De La Motte Rouge, T and Pistilli, B and Brain, E and Pasquier, D and Debled, M and Thery, JC and Gonçalves, A and Desmoulins, I and Levy, C and Uwer, L and Ferrero, JM and Eymard, JC and Mouret-Reynier, MA and Patsouris, A and Frenel, JS and Petit, T and Chevrot, M and Bachelot, T and Guiu, S}, title = {Impact of lobular versus ductal histology on overall survival in metastatic breast cancer: a French retrospective multicentre cohort study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {164}, number = {}, pages = {70-79}, doi = {10.1016/j.ejca.2021.12.031}, pmid = {35176614}, issn = {1879-0852}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/pathology ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: The impact of the histological lobular subtype on overall survival (OS) in metastatic breast cancer (MBC) is still under debate, with very few data available.

PATIENTS AND METHODS: Using the French national multicentre Epidemiological Strategy and Medico Economics [ESME]) data platform, the primary objective was to compare the OS of patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) MBC, with adjustment on the main prognostic factors using two approaches: multivariable analysis and matching with a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1) and describe patients and tumour characteristics.

RESULTS: Of the 16,703 patients with MBC in the ESME database, 13,111 met all inclusion criteria for the present analysis. One-thousand eight-hundred and four (13.8%) patients had ILC and 11.307 (86.2%) IDC. In the multivariable analysis, patients with ILC had a worse OS [hazard ratio (HR): 1.31; 95%CI 1.20-1.42; p < 0.0001] and a worse PFS1 (HR: 1.15; 95%CI 1.07-1.22; p < 0.0001) as compared with those with IDC, independently of hormone receptor and HER2 status. Interestingly, OS was better (HR 0.79; 95% confidence interval [CI] 0.64-0.98; p = 0.0302), worse (HR: 1.17; 95%CI 1.08-1.27; p = 0.0001) or similar (HR: 0.88; 95%CI 0.67-1.15; p = 0.3455) in patients with ILC with triple-negative, hormone receptor-positive/HER2-negative and HER2-positive MBC, respectively, compared with patients with IDC.

CONCLUSION: Lobular histology is an independent adverse prognostic factor among women with MBC. ILC MBC could be considered a specific entity. Dedicated prospective studies are needed to tailor the management of these patients.}, } @article {pmid35175871, year = {2022}, author = {Nagar, S and Mikulincer, M and Nitsan, G and Ben-David, BM}, title = {Safe and Sound: The Effects of Experimentally Priming the Sense of Attachment Security on Pure-Tone Audiometric Thresholds Among Young and Older Adults.}, journal = {Psychological science}, volume = {33}, number = {3}, pages = {424-432}, doi = {10.1177/09567976211042008}, pmid = {35175871}, issn = {1467-9280}, mesh = {Aged ; Audiometry, Pure-Tone/methods ; *Hearing ; Humans ; *Noise ; Sound ; }, abstract = {Attachment security has consistently been found to correlate with relaxed exploration, openness, and mindful attention to incoming information. The present studies explored whether contextually infusing a sense of attachment security (security priming) can improve hearing in young and older adults. In Study 1, participants (29 young, 30 older) performed a standardized pure-tone audiometric-thresholds test twice. In the security-priming condition, a picture of a participant's security-enhancing figure was presented throughout the task. In the control condition, a picture of an unknown person (matched in sex, age, and facial expression) was used as a neutral prime. Study 2 (14 young, 14 older) was almost identical, except that it was preregistered and the neutral prime was a circle. In both studies, participants performed better (had lower hearing thresholds) in the security-priming condition. The current study is the first to show that attachment security improves sensory perception, and these results have meaningful implications for theory and clinical hearing tests.}, } @article {pmid35172312, year = {2022}, author = {Shashar, M and Nacasch, N and Grupper, A and Benchetrit, S and Halperin, T and Erez, D and Rozenberg, I and Shitrit, P and Sela, Y and Wand, O and Cohen-Hagai, K}, title = {Humoral Response to Pfizer BNT162b2 Vaccine Booster in Maintenance Hemodialysis Patients.}, journal = {American journal of nephrology}, volume = {53}, number = {2-3}, pages = {207-214}, pmid = {35172312}, issn = {1421-9670}, mesh = {BNT162 Vaccine ; *COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; Renal Dialysis ; SARS-CoV-2 ; *Vaccines ; }, abstract = {INTRODUCTION: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine.

METHODS: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose.

RESULTS: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response.

CONCLUSIONS: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule.}, } @article {pmid35171689, year = {2022}, author = {Carl, M and Icht, M and Ben-David, BM}, title = {A Cross-Linguistic Validation of the Test for Rating Emotions in Speech: Acoustic Analyses of Emotional Sentences in English, German, and Hebrew.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {65}, number = {3}, pages = {991-1000}, doi = {10.1044/2021_JSLHR-21-00205}, pmid = {35171689}, issn = {1558-9102}, mesh = {Acoustics ; *COVID-19 ; Emotions ; Humans ; Language ; Linguistics ; SARS-CoV-2 ; Speech ; *Speech Perception ; }, abstract = {PURPOSE: The Test for Rating Emotions in Speech (T-RES) has been developed in order to assess the processing of emotions in spoken language. In this tool, spoken sentences, which are composed of emotional content (anger, happiness, sadness, and neutral) in both semantics and prosody in different combinations, are rated by listeners. To date, English, German, and Hebrew versions have been developed, as well as online versions, iT-RES, to adapt to COVID-19 social restrictions. Since the perception of spoken emotions may be affected by linguistic (and cultural) variables, it is important to compare the acoustic characteristics of the stimuli within and between languages. The goal of the current report was to provide cross-linguistic acoustic validation of the T-RES.

METHOD: T-RES sentences in the aforementioned languages were acoustically analyzed in terms of mean F0, F0 range, and speech rate to obtain profiles of acoustic parameters for different emotions.

RESULTS: Significant within-language discriminability of prosodic emotions was found, for both mean F0 and speech rate. Similarly, these measures were associated with comparable patterns of prosodic emotions for each of the tested languages and emotional ratings.

CONCLUSIONS: The results demonstrate the lack of dependence of prosody and semantics within the T-RES stimuli. These findings illustrate the listeners' ability to clearly distinguish between the different prosodic emotions in each language, providing a cross-linguistic validation of the T-RES and iT-RES.}, } @article {pmid35169198, year = {2022}, author = {Sangha, GS and Hu, B and Li, G and Fox, SE and Sholl, AB and Brown, JQ and Goergen, CJ}, title = {Assessment of photoacoustic tomography contrast for breast tissue imaging using 3D correlative virtual histology.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2532}, pmid = {35169198}, issn = {2045-2322}, support = {P30 CA023168/CA/NCI NIH HHS/United States ; R33 CA196457/CA/NCI NIH HHS/United States ; T32 DK101001/DK/NIDDK NIH HHS/United States ; R01 CA222831/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Phantoms, Imaging ; Photoacoustic Techniques/*methods ; Ultrasonography, Mammary/*methods ; }, abstract = {Current breast tumor margin detection methods are destructive, time-consuming, and result in significant reoperative rates. Dual-modality photoacoustic tomography (PAT) and ultrasound has the potential to enhance breast margin characterization by providing clinically relevant compositional information with high sensitivity and tissue penetration. However, quantitative methods that rigorously compare volumetric PAT and ultrasound images with gold-standard histology are lacking, thus limiting clinical validation and translation. Here, we present a quantitative multimodality workflow that uses inverted Selective Plane Illumination Microscopy (iSPIM) to facilitate image co-registration between volumetric PAT-ultrasound datasets with histology in human invasive ductal carcinoma breast tissue samples. Our ultrasound-PAT system consisted of a tunable Nd:YAG laser coupled with a 40 MHz central frequency ultrasound transducer. A linear stepper motor was used to acquire volumetric PAT and ultrasound breast biopsy datasets using 1100 nm light to identify hemoglobin-rich regions and 1210 nm light to identify lipid-rich regions. Our iSPIM system used 488 nm and 647 nm laser excitation combined with Eosin and DRAQ5, a cell-permeant nucleic acid binding dye, to produce high-resolution volumetric datasets comparable to histology. Image thresholding was applied to PAT and iSPIM images to extract, quantify, and topologically visualize breast biopsy lipid, stroma, hemoglobin, and nuclei distribution. Our lipid-weighted PAT and iSPIM images suggest that low lipid regions strongly correlate with malignant breast tissue. Hemoglobin-weighted PAT images, however, correlated poorly with cancerous regions determined by histology and interpreted by a board-certified pathologist. Nuclei-weighted iSPIM images revealed similar cellular content in cancerous and non-cancerous tissues, suggesting malignant cell migration from the breast ducts to the surrounding tissues. We demonstrate the utility of our nondestructive, volumetric, region-based quantitative method for comprehensive validation of 3D tomographic imaging methods suitable for bedside tumor margin detection.}, } @article {pmid35159368, year = {2022}, author = {Helm, J and Drukewitz, S and Poser, I and Richter, S and Friedemann, M and William, D and Mohr, H and Nölting, S and Robledo, M and Bornstein, SR and Eisenhofer, G and Bechmann, N}, title = {Treatment of Pheochromocytoma Cells with Recurrent Cycles of Hypoxia: A New Pseudohypoxic In Vitro Model.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159368}, issn = {2073-4409}, support = {CRC/Transregio 205/2, Project No. 314061271 - TRR205//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adrenal Gland Neoplasms/pathology/*therapy ; Animals ; Cell Hypoxia ; Cell Proliferation ; Disease Models, Animal ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Pheochromocytoma/pathology/*therapy ; Rats ; }, abstract = {Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most of the commonly used in vitro models lack characteristics of these pseudohypoxic tumors, including elevated expression of hypoxia-inducible factor (HIF) 2α. To address this shortcoming, we investigated whether recurrent hypoxia cycles lead to continuous activation of hypoxia pathways under normoxic conditions and whether this pseudohypoxia is associated with increased cellular aggressiveness. Rat pheochromocytoma cells (PC12) were incubated under hypoxia for 24 h every 3-4 days, up to 20 hypoxia-reoxygenation cycles, resulting in PC12 Z20 cells. PC12 Z20 control cells were obtained by synchronous cultivation under normoxia. RNA sequencing revealed upregulation of HIF2α in PC12 Z20 cells and a pseudohypoxic gene signature that overlapped with the gene signature of pseudohypoxic PPGLs. PC12 Z20 cells showed a higher growth rate, and the migration and adhesion capacity were significantly increased compared with control cells. Changes in global methylation, together with the pseudohypoxic conditions, may be responsible for the increased aggressiveness of this new model. The established sub-cell line with characteristics of pseudohypoxic PPGLs represent a complementary model for further investigations, for example, with regard to new therapeutic approaches.}, } @article {pmid35159086, year = {2022}, author = {Pantazopoulos, H and Diop, MK and Grosset, AA and Rouleau-Gagné, F and Al-Saleh, A and Boblea, T and Trudel, D}, title = {Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, pmid = {35159086}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.}, } @article {pmid35159065, year = {2022}, author = {Chen, YC and Chen, WM and Chiang, MF and Shia, BC and Wu, SY}, title = {Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.}, journal = {Cancers}, volume = {14}, number = {3}, pages = {}, pmid = {35159065}, issn = {2072-6694}, abstract = {PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC).

METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching.

RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001).

CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.}, } @article {pmid35157140, year = {2022}, author = {Seyrek, N and Hollemans, E and Andrinopoulou, ER and Osanto, S and Pelger, RCM and van der Poel, HG and Bekers, E and Remmers, S and Schoots, IG and van Leenders, GJLH}, title = {Alternative prostate cancer grading systems incorporating percent pattern 4/5 (IQ-Gleason) and cribriform architecture (cGrade) improve prediction of outcome after radical prostatectomy.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {480}, number = {6}, pages = {1149-1157}, pmid = {35157140}, issn = {1432-2307}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Male ; Neoplasm Grading ; Prostate/pathology ; Prostatectomy ; *Prostatic Neoplasms/pathology ; }, abstract = {Percentage Gleason pattern 4, invasive cribriform and/or intraductal carcinoma (IC/IDC) and minor pattern 5 are recognized as independent parameters for prostate cancer outcome, but are not incorporated in current grade groups (GGs). Two proof-of-principle studies have proposed alternative grading schemes based on percentage Gleason pattern 4/5 (integrated quantitative Gleason score; IQ-Gleason) and IC/IDC presence (cribriform grade; cGrade). Our objective was to compare the performance of GG, IQ-Gleason and cGrade for predicting biochemical recurrence and metastasis after radical prostatectomy (RP). RP specimens of 1064 patients were pathologically reviewed and graded according to the three schemes. Discriminative power for prediction of biochemical recurrence-free (BCRFS) and metastasis-free (MFS) survival was compared using Harrell's c-index. The GG distribution at RP was 207 (19.4%) GG1, 472 (44.4%) GG2, 126 (11.8%) GG3, 140 (13.2%) GG4 and 119 (11.2%) GG5. Grading according to 5-tier IQ-Gleason and cGrade systems led to categorical shifts in 49.8% and 29.7% of cases, respectively. Continuous IQ-Gleason had the best performance for predicting BCRFS (c-index 0.743, 95% confidence interval (CI) 0.715-0.771), followed by cGrade (c-index 0.738, 95%CI 0.712-0.759), 5-tier categorical IQ-Gleason (c-index 0.723, 95%CI 0.695-0.750) and GG (c-index 0.718, 95%CI 0.691-0.744). Continuous IQ-Gleason (c-index 0.834, 95%CI 0.802-0.863) and cGrade (c-index 0.834, 95%CI 0.808-0.866) both had better predictive value for MFS than categorical IQ-Gleason (c-index 0.823, 95%CI 0.788-0.857) and GG (c-index 0.806, 95%CI 0.777-0.839). In conclusion, the performance of prostate cancer grading can be improved by alternative grading schemes incorporating percent Gleason pattern 4/5 and IC/IDC.}, } @article {pmid35155685, year = {2022}, author = {Zhang, L and Du, J and Song, Q and Zhang, C and Wu, X}, title = {A Novel In Situ Dendritic Cell Vaccine Triggered by Rose Bengal Enhances Adaptive Antitumour Immunity.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {1178874}, pmid = {35155685}, issn = {2314-7156}, mesh = {Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*immunology ; Cell Differentiation ; Dendritic Cells/*immunology/transplantation ; Humans ; Immunization ; Immunotherapy/*methods ; Lung Neoplasms/*immunology/secondary ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma/*immunology/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Rose Bengal/metabolism ; }, abstract = {Dendritic cell- (DC-) based vaccination has emerged as a promising antitumour immunotherapy. However, overcoming immune tolerance and immunosuppression in the tumour microenvironment (TME) is still a great challenge. Recent studies have shown that Rose Bengal (RB) can effectively induce immunogenic cell death (ICD) in cancer cells, presenting whole tumour antigens for DC processing and presentation. However, the synergistic antitumour effect of combining intralesional RB with immature DCs (RB-iDCs) remains unclear. In the present study, we investigated whether RB-iDCs have superior antitumour effects compared with either single agent and evaluated the immunological mechanism of RB-iDCs in a murine lung cancer model. The results showed that intralesional RB-iDCs suppressed subcutaneous tumour growth and lung metastasis, which resulted in 100% mouse survival and significantly increased TNF-α production by CD8[+] T cells. These effects were closely related to the induction of the expression of distinct ICD hallmarks by RB in both bulk cancer cells and cancer stem cells (CSCs), especially calreticulin (CRT), thus enhancing immune effector cell (i.e., CD4[+], CD8[+], and memory T cells) infiltration and attenuating the accumulation of immunosuppressive cells (i.e., Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs)) in the TME. This study reveals that the RB-iDC vaccine can synergistically destroy the primary tumour, inhibit distant metastasis, and prevent tumour relapse in a lung cancer mouse model, which provides important preclinical data for the development of a novel combinatorial immunotherapy.}, } @article {pmid35155209, year = {2021}, author = {Liu, C and Zhou, J and Chang, C and Zhi, W}, title = {Feasibility of Shear Wave Elastography Imaging for Evaluating the Biological Behavior of Breast Cancer.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {820102}, pmid = {35155209}, issn = {2234-943X}, abstract = {OBJECTIVE: To explore the feasibility of shear wave elastography (SWE) parameters for assessing the biological behavior of breast cancer.

MATERIALS AND METHODS: In this prospective study, 224 breast cancer lesions in 216 female patients were examined by B-mode ultrasound and shear wave elastography in sequence. The maximum size (Smax) of the lesion was measured by B-mode ultrasound, and then shear wave elastography was performed on this section to obtain relevant parameters, including maximum elasticity (Emax), mean elasticity (Emean), standard deviation of elasticity (SD), and the area ratio of shear wave elastography to B-mode ultrasound (AR). The relationship between SWE parameters and pathological type, histopathological classification, histological grade, lymphovascular invasion status (LVI), axillary lymph node status (ALN), and immunohistochemistry of breast cancer lesions was performed according to postoperative pathology.

RESULTS: In the univariate analysis, the pathological type and histopathological classification of breast cancer were not significantly associated with SWE parameters; with an increase in the histological grade of invasive ductal carcinoma (IDC), SD (p = 0.016) and Smax (p = 0.000) values increased. In the ALN-positive group, Smax (p = 0.004) was significantly greater than in the ALN-negative group; Smax (p = 0.003), Emax (p = 0.034), and SD (p = 0.045) were significantly higher in the LVI-positive group than in the LVI-negative group; SD (p = 0.043, p = 0.047) and Smax (p = 0.000, p = 0.000) were significantly lower in the ER[+] and PR[+] groups than in the ER[-] and PR[-] groups, respectively; AR (p = 0.032) was significantly higher in the ER[+] groups than in the ER[-] groups, and Smax (p = 0.002) of the HER2[+] group showed higher values than that of the HER2[-] group; Smax (p = 0.000), SD (p = 0.006), and Emax (p = 0.004) of the Ki-67 high-expression group showed significantly higher values than those of the Ki-67 low-expression group. In the multivariate analysis, Ki-67 was an independent factor of Smax (p = 0.005), Emax (p = 0.004), and SD (p = 0.006); ER was an independent influencing factor of Smax (p = 0.000) and AR (p = 0.032). LVI independently influences Smax (p = 0.006).

CONCLUSIONS: The SWE parameters Emax, SD, and AR can be used to evaluate the biological behavior of breast cancer.}, } @article {pmid35151601, year = {2022}, author = {Jeyapala, R and Kamdar, S and Olkhov-Mitsel, E and Zlotta, A and Fleshner, N and Visakorpi, T and van der Kwast, T and Bapat, B}, title = {Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients.}, journal = {Clinical genitourinary cancer}, volume = {20}, number = {3}, pages = {e217-e226}, doi = {10.1016/j.clgc.2022.01.003}, pmid = {35151601}, issn = {1938-0682}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Humans ; Male ; Neoplasm Recurrence, Local/pathology ; Prostate-Specific Antigen ; Prostatectomy/methods ; *Prostatic Neoplasms/pathology ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings.

MATERIALS AND METHODS: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts.

RESULTS: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients.

CONCLUSION: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.}, } @article {pmid35151355, year = {2022}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.}, journal = {Radiation oncology (London, England)}, volume = {17}, number = {1}, pages = {33}, pmid = {35151355}, issn = {1748-717X}, mesh = {Adult ; Aged ; Female ; Heart Failure/*complications ; Humans ; *Mastectomy, Simple ; Middle Aged ; Radiotherapy, Adjuvant ; Survival Rate ; Unilateral Breast Neoplasms/*complications/*mortality/*radiotherapy/surgery ; Young Adult ; }, abstract = {BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).

RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P = 0.0356) and 0.89 (0.54-1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group.

CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.}, } @article {pmid35141340, year = {2022}, author = {Ângelo, ACLPG and de Campos Azevedo, CI}, title = {Donor-Site Morbidity After Autologous Fascia Lata Harvest for Arthroscopic Superior Capsular Reconstruction: A Midterm Follow-up Evaluation.}, journal = {Orthopaedic journal of sports medicine}, volume = {10}, number = {2}, pages = {23259671211073133}, pmid = {35141340}, issn = {2325-9671}, abstract = {BACKGROUND: Autologous fascia lata (AFL) graft use in arthroscopic superior capsular reconstruction (ASCR) is effective for the treatment of irreparable rotator cuff tears (RCTs). Although donor-site morbidity (DSM) is a recurrent argument against AFL graft use, scientific evidence for this argument is lacking.

PURPOSE: To report the midterm clinical follow-up evaluation of DSM in ASCR using minimally invasively harvested AFL grafts and compare thigh function and patient satisfaction with those of an unharvested control group.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Of 66 consecutive patients who underwent ASCR using a minimally invasively harvested AFL graft, 39 patients with a minimum follow-up of 24 months were retrospectively evaluated (ASCR group) and compared with 39 randomly selected patients who underwent arthroscopic RCT repair by the same surgeons (control group). The functional outcomes of both thighs were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Patient satisfaction was evaluated using the Patient Scar Assessment Questionnaire (PSAQ) and a subjective questionnaire. Pain was quantified using a visual analog scale (VAS).

RESULTS: The ASCR group had a mean age of 65 years (range, 51-77 years) and a mean follow-up of 47 months (range, 24-66 months). The WOMAC score in the harvested thigh differed by 0.8% from that in the contralateral thigh (P = .002). The mean PSAQ score differed by 6 points from the minimum PSAQ score (P < .001). Overall, 95% of the patients indicated that they would undergo the same surgery again and that the shoulder outcome compensated for the thigh symptoms. There was no significant association between the presence of residual thigh symptoms and the willingness to undergo the same surgery again (P = .354). The mean VAS score in the harvested thigh was 0.6 (range, 0-5). There was no significant difference in the average WOMAC score or VAS score between groups (P = .684 and P = .148, respectively).

CONCLUSION: Despite the proportion of residual symptoms, the associated functional effects were small and not clinically significant, and the vast majority of patients were accepting of the harvest symptoms given the improvement in shoulder function.}, } @article {pmid35137951, year = {2022}, author = {Weiser, R and Polychronopoulou, E and Hatch, SS and Haque, W and Ghani, HA and He, J and Kuo, YF and Gradishar, WJ and Klimberg, VS}, title = {Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.}, journal = {Cancer}, volume = {128}, number = {9}, pages = {1738-1747}, doi = {10.1002/cncr.34127}, pmid = {35137951}, issn = {1097-0142}, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/drug therapy/genetics ; *Carcinoma, Lobular/drug therapy/genetics/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients.

METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy.

RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease.

CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.

LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.}, } @article {pmid35137941, year = {2022}, author = {Jozanovic, V and Huic, D}, title = {Incidental detection of breast cancer by 18F-fluorocholine PET/CT performed for primary hyperparathyroidism.}, journal = {Nuclear medicine review. Central & Eastern Europe}, volume = {25}, number = {1}, pages = {66-67}, doi = {10.5603/NMR.a2022.0013}, pmid = {35137941}, issn = {1644-4345}, mesh = {*Breast Neoplasms/diagnostic imaging ; Choline/analogs & derivatives ; Female ; Humans ; *Hyperparathyroidism, Primary/diagnostic imaging ; Parathyroid Glands ; Positron Emission Tomography Computed Tomography ; Technetium Tc 99m Sestamibi ; }, abstract = {We present a case report of incidental detection of breast cancer in a female patient referred for 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) due to primary hyperparathyroidism. This imaging method was recently shown as more sensitive for the detection of metabolically hyperactive parathyroid glands than neck ultrasound and (2-metoksyizobutyloizonitryl labeled with technetium-99m) [99mTc]MIBI. Increased accumulation of FCH was found in the hyperactive parathyroid gland and unexpectedly in the right breast lesion. The surgery confirmed parathyroid adenoma. One month later right upper medial quadrantectomy confirmed breast carcinoma - a combination of invasive ductal carcinoma and intracystic papillary breast carcinoma. To the best of our knowledge, this is the first reporting of simultaneous detection of parathyroid adenoma and breast cancer by using 18F-fluorocholine PET/CT.}, } @article {pmid35137931, year = {2022}, author = {Sarikaya, I and Sarikaya, A and Albatineh, AN and Tastekin, E and Sezer, YA}, title = {Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.}, journal = {Nuclear medicine review. Central & Eastern Europe}, volume = {25}, number = {1}, pages = {6-11}, doi = {10.5603/NMR.a2022.0003}, pmid = {35137931}, issn = {1644-4345}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; }, abstract = {BACKGROUND: Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS.

MATERIAL AND METHODS: FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS.

RESULTS: This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively).

CONCLUSIONS: Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.}, } @article {pmid35137713, year = {2023}, author = {Fredericks, S}, title = {Integrating Interactive Digital Content Into Existing Professional Development Programs for Nurses: A Brief Discussion Paper.}, journal = {Journal for nurses in professional development}, volume = {39}, number = {3}, pages = {150-155}, pmid = {35137713}, issn = {2169-981X}, mesh = {Humans ; Pandemics ; *COVID-19 ; *Education, Nursing ; *Education, Distance ; *Nurses ; }, abstract = {Current nursing professional development programs include online education related to caring for COVID-19-positive patients. However, these resources failed to attract significant uptake of knowledge acquisition mainly because of poorly structured web pages. This discussion paper presents a unique perspective to designing professional development programs for frontline nurses working during the COVID-19 pandemic and beyond through the use of interactive digital content (IDC). An overview of IDC is provided, followed by strategies for transforming existing nursing professional development education into IDC.}, } @article {pmid35136530, year = {2021}, author = {Yıldırım, M and Artas, H}, title = {A Case of İntrapancreatic Accessory Spleen Mimicking a Pancreatic Metastasis on the [18] F-FDG PET/CT Scan: A Case with Breast Cancer.}, journal = {The Indian journal of radiology & imaging}, volume = {31}, number = {4}, pages = {1062-1064}, pmid = {35136530}, issn = {0971-3026}, abstract = {The accessory spleen is a focus of splenic tissue which is separated from the main of the spleen. Although accessory spleens are generally recognized on computed tomography (CT), intrapancreatic accessory spleen (IPAS) may be mistaken for other pancreatic tail lesions. We report a case of IPAS mimicking a pancreatic metastasis on the [18] F-fluorodeoxyglucose positron emission tomography/computed tomography ([18] F-FDG PET/CT). A 41-year-old with diagnosed breast cancer (invasive ductal carcinoma) woman patient underwent an [18] F-FDG PET/CT for metastasis screening and staging. [18] F-FDG PET/CT showed a focal uptake in the pancreatic tail. The patient underwent a contrast-enhanced CT and magnetic resonance imaging (MRI) for lesion characterization. The density and intensity of lesion were similar to spleen on all phases and all sequences. The lesion was evaluated as IPAS. The diagnosis was confirmed by endoscopic ultrasound (EUS) biopsy. A case of IPAS positive at [18] F-FDG PET/CT could not found in the literature. We present a case of IPAS mimicking a pancreatic metastasis positive at [18] F-FDG PET/CT.}, } @article {pmid35132340, year = {2022}, author = {Alkhathami, AG and Hadi, A and Alfaifi, M and Alshahrani, MY and Verma, AK and Beg, MMA}, title = {Serum-Based lncRNA ANRIL, TUG1, UCA1, and HIT Expressions in Breast Cancer Patients.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {9997212}, pmid = {35132340}, issn = {1875-8630}, mesh = {Breast Neoplasms/*blood/metabolism ; Female ; Humans ; Middle Aged ; RNA, Long Noncoding/biosynthesis/*blood ; }, abstract = {Breast cancer is a heterogeneous disease and is the most common and prevalent form of malignancy diagnosed in women. lncRNAs are found to be frequently dysregulated in cancer, and its expression plays a critical role in tumorigenesis. The study included 100 histopathologically confirmed, newly diagnosed untreated patients of invasive ductal carcinoma (IDC) of breast cancer patients and 100 healthy subjects. After blood collection, the serum was separated and total RNA was extracted, cDNA was synthesized using 100 ng of total RNA, and lncRNA (ANRIL, TUG1, UCA1, and HIT) expression was analyzed. Increased ANRIL (3.83-fold), TUG1 (7.64-fold), UCA1 (7.82-fold), and HIT (3.31-fold) expressions were observed in breast cancer patients compared to healthy controls. Relative expression of lncRNAs UCA-1 (p = 0.010) and HIT-1 (p < 0.0001) was significantly elevated in patients with advanced breast cancer stage compared to those with early-stage disease. While lncRNA TUG-1 expression was found to be higher in patients with early-stage tumors than those with advanced-stage tumors (p = 0.06), lncRNA ANRIL showed increased expression in patients with PR positive status (p = 0.04). However, we found a significant difference in lncRNA HIT expression in HER-2 positive breast cancer patients compared to HER-2 negative breast cancer patients (p = 0.005). An increase in the expression of serum lncRNAs ANRIL (p < 0.0001), UCA-1 (p = 0.004), and HIT (p < 0.0001) was observed in the distant organ metastatic breast cancer patients. In the ROC curve concerning lymph node involvement, the sensitivity and specificity of lncRNA HIT were 68% and 58%, respectively (p value = 0.007). In the ROC curve w.r.t. stages of disease, the sensitivity and specificity of lncRNA HIT were 80% and 50%, respectively (p value < 0.0001). Better sensitivity and specificity were observed for lncRNA HIT (sensitivity 91% and specificity 78%; p value < 0.0001) and ANRIL (sensitivity 70% and specificity 60%; p value < 0.0001) w.r.t distant organ metastases.}, } @article {pmid35130270, year = {2022}, author = {Khanam, R and Applegate, J and Nisar, I and Dutta, A and Rahman, S and Nizar, A and Ali, SM and Chowdhury, NH and Begum, F and Dhingra, U and Tofail, F and Mehmood, U and Deb, S and Ahmed, S and Muhammad, S and Das, S and Ahmed, S and Mittal, H and Minckas, N and Yoshida, S and Bahl, R and Jehan, F and Sazawal, S and Baqui, AH}, title = {Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.}, journal = {PloS one}, volume = {17}, number = {2}, pages = {e0263091}, pmid = {35130270}, issn = {1932-6203}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; Asia/epidemiology ; Bangladesh/epidemiology ; Cohort Studies ; Depression/complications/*epidemiology ; Female ; Humans ; Infant, Newborn ; Pakistan/epidemiology ; Pregnancy ; Pregnancy Complications/epidemiology/psychology ; Pregnancy Outcome/*epidemiology/psychology ; Premature Birth/*epidemiology ; Prenatal Care/statistics & numerical data ; Risk Factors ; Young Adult ; }, abstract = {INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth.

METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of ≥12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).

RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of ≥2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).

CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.}, } @article {pmid35127926, year = {2022}, author = {Wen, W and Jiang, H and Wen, HY and Peng, YL}, title = {Metastasis to the thyroid gland from primary breast cancer presenting as diffuse goiter: A case report and review of literature.}, journal = {World journal of clinical cases}, volume = {10}, number = {3}, pages = {1106-1115}, pmid = {35127926}, issn = {2307-8960}, abstract = {BACKGROUND: Metastasis to the thyroid gland (TM) from primary breast cancer is uncommon and usually presents as thyroid nodules; however, diffuse goiter without thyroid nodules is the first sign of TM in rare cases. Skip metastases (SMs) to the lymph nodes in breast cancer, defined as discontiguous higher-level metastases in the absence of lower levels of contiguous metastases, have been reported in the contralateral cervical area of the primary tumor site in rare cases.

CASE SUMMARY: A 49-year-old previously healthy Chinese woman was diagnosed with right lateral invasive ductal carcinoma and underwent neoadjuvant chemotherapy treatment and bilateral mastectomy with axillary lymph node dissection. No malignancy of the left breast or axillary or distant metastases were identified preoperatively. However, enlarged left cervical lymph nodes were detected 36 mo after surgery, and rapidly enlarging thyroid glands without nodules were detected 42 mo after surgery. Fine-needle aspiration cytology was performed on the left cervical lymph nodes and left lobe of the thyroid, which were both revealed to contain metastases from the primary breast cancer. Additionally, the immunostaining profiles changed in the process of metastases. The patient was discharged with the NP (vinorelbine and cisplatin) regimen for subsequent treatment, and stable disease was determined when the curative effect was evaluated.

CONCLUSION: Diffuse goiter may be the first sign of TM, and enlarged lymph nodes in the contralateral cervical area may be SMs of primary breast cancer.}, } @article {pmid35125891, year = {2022}, author = {Han, BY and Xu, XL and Zhu, XZ and Han, XC and Hu, X and Ling, H}, title = {Clinicopathological Characteristics and Survival Outcomes of Mammary Paget's Disease: A Retrospective Study Based on a Chinese Population.}, journal = {Cancer management and research}, volume = {14}, number = {}, pages = {237-247}, pmid = {35125891}, issn = {1179-1322}, abstract = {BACKGROUND: Mammary Paget's disease (PD) is a rare type of breast cancer. Most cases of PD are presented with underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IDC). This study aimed to investigate the clinicopathological characteristics and survival outcomes of PD patients.

MATERIALS AND METHODS: A total of 406 patients diagnosed with PD with IDC/DCIS at Fudan University Shanghai Cancer Center (FUSCC) were recruited as the PD group, 1218 patients diagnosed with IDC/DCIS alone during the same period were selected as the non-PD group, and the clinicopathological results of these two groups were compared. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the clinicopathological features between PD and non-PD patients for validation.

RESULTS: Compared with the non-PD group, the PD group was much more likely to have larger (≥2 cm: 43.1% vs 35.5%, P < 0.001), less hormone receptor (HR)-positive (68.5% vs 26.6%, P < 0.001), more human epidermal growth factor receptor-2 (HER-2)-positive (70.7% vs 27.5%, P < 0.001) and higher Ki-67 proportion (51.5% vs 42.5%, P < 0.001) tumors. The HER-2 overexpression subtype accounted for the largest proportion in the PD-IDC group and the lowest proportion in the non-PD-IDC group (54% vs 8%, P < 0.01). Moreover, the PD group had significantly worse disease-free survival (DFS) than the non-PD group (5-year DFS: 91.8% vs 97.3%, P = 0.001), and the SEER database showed a similar trend. Univariate and multivariate Cox regression analyses demonstrated that PD was an independent poor-risk factor. Our matched study showed that the PD group had worse survival than the non-PD group after excluding age, HR, HER-2, tumor size and lymph node status.

CONCLUSION: PD with IDC/DCIS is associated with more aggressive tumor characteristics and worse survival outcomes. More than half of PD breast cancers are HER-2 overexpression subtype. PD is an independent poor-risk factor for breast cancer survival.}, } @article {pmid35123076, year = {2022}, author = {Patel, V and Gleeson, PK and Delaney, K and Ralston, SJ and Feldman, S and Fadugba, O}, title = {Safety and outcomes of penicillin allergy evaluation in pregnant women.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {128}, number = {5}, pages = {568-574}, doi = {10.1016/j.anai.2022.01.032}, pmid = {35123076}, issn = {1534-4436}, mesh = {Anti-Bacterial Agents/adverse effects ; *Drug Hypersensitivity/diagnosis/drug therapy ; Female ; Humans ; Male ; Penicillins/adverse effects ; Pregnancy ; *Pregnancy Complications, Infectious/drug therapy ; Pregnant Women ; Skin Tests/methods ; }, abstract = {BACKGROUND: Penicillin allergy in pregnancy is associated with increased morbidity and the use of less effective antibiotics. Penicillin allergy evaluation in pregnancy is now recommended as per obstetrical guidelines but remains infrequent.

OBJECTIVE: We studied pregnant women who underwent penicillin allergy evaluation in an allergy clinic to assess the effectiveness and safety of penicillin skin testing (PST) and incremental drug challenge (IDC) in pregnancy.

METHODS: Index drug reactions, PST, and IDC results were reviewed. Antibiotic use, pregnancy outcomes, and pregnancy complications were compared with a control cohort of pregnant women with penicillin allergy who did not undergo allergy evaluation before delivery.

RESULTS: Penicillin allergy was evaluated in 136 women. Culprit drugs included penicillin (37%), amoxicillin (30%), and unknown (20%). Index reactions occurred greater than 5 years ago in 91%, and these reactions were cutaneous or unknown in 92%. Of the 133 patients who underwent skin testing, 131 (99%) had negative or equivocal results and proceeded to incremental challenge. All 131 women passed penicillin IDC. Of the 69 women who ultimately used intrapartum beta-lactam antibiotics, all but 1 patient tolerated them. Women who underwent penicillin allergy evaluation did not have an increased risk of cesarean delivery or other pregnancy complications when compared with women without penicillin allergy evaluation.

CONCLUSION: PST and IDC can be safely conducted in pregnant women. When evaluated as low risk, most women tolerate IDC and can receive penicillin intrapartum without adverse reactions or negative pregnancy outcomes.}, } @article {pmid35122559, year = {2022}, author = {Abraham, E and Feldman, R}, title = {The Neural Basis of Human Fatherhood: A Unique Biocultural Perspective on Plasticity of Brain and Behavior.}, journal = {Clinical child and family psychology review}, volume = {25}, number = {1}, pages = {93-109}, pmid = {35122559}, issn = {1573-2827}, mesh = {Brain/physiology ; Child ; *Father-Child Relations ; *Fathers/psychology ; Female ; Humans ; Male ; Parenting/psychology ; Paternal Behavior/physiology/psychology ; Pregnancy ; }, abstract = {With the growing involvement of fathers in childrearing and the application of neuroscientific tools to research on parenting, there is a need to understand how a father's brain and neurohormonal systems accommodate the transition to parenthood and how such neurobiological changes impact children's mental health, sociality, and family functioning. In this paper, we present a theoretical model on the human father's brain and the neural adaptations that take place when fathers assume an involved role. The neurobiology of fatherhood shows great variability across individuals, societies, and cultures and is shaped to a great extent by bottom-up caregiving experiences and the amount of childrearing responsibilities. Mechanisms of mother-father coparental brain coordination and hormonal correlates of paternal behavior are detailed. Adaptations in the father's brain during pregnancy and across the postpartum year carry long-term implications for children's emotion regulation, stress management, and symptom formation. We propose a new conceptual model of HEALthy Father Brain that describes how a father's brain serves as a source of resilience in the context of family adversity and its capacity to "heal", protect, and foster social brain maturation and functionality in family members via paternal sensitivity, attunement, and support, which, in turn, promote child development and healthy family functioning. Father's brain provides a unique model on neural plasticity as sustained by committed acts of caregiving, thereby affording a novel perspective on the brain basis of human affiliation.}, } @article {pmid35120589, year = {2022}, author = {Loft, A and Schmidt, SF and Caratti, G and Stifel, U and Havelund, J and Sekar, R and Kwon, Y and Sulaj, A and Chow, KK and Alfaro, AJ and Schwarzmayr, T and Rittig, N and Svart, M and Tsokanos, FF and Maida, A and Blutke, A and Feuchtinger, A and Møller, N and Blüher, M and Nawroth, P and Szendrödi, J and Færgeman, NJ and Zeigerer, A and Tuckermann, J and Herzig, S}, title = {A macrophage-hepatocyte glucocorticoid receptor axis coordinates fasting ketogenesis.}, journal = {Cell metabolism}, volume = {34}, number = {3}, pages = {473-486.e9}, doi = {10.1016/j.cmet.2022.01.004}, pmid = {35120589}, issn = {1932-7420}, mesh = {Animals ; *Fasting/metabolism ; Hepatocytes/metabolism ; Humans ; Ketone Bodies/metabolism ; Liver/metabolism ; Macrophages/metabolism ; Mice ; Mice, Knockout ; PPAR alpha/metabolism ; *Receptors, Glucocorticoid/metabolism ; }, abstract = {Fasting metabolism and immunity are tightly linked; however, it is largely unknown how immune cells contribute to metabolic homeostasis during fasting in healthy subjects. Here, we combined cell-type-resolved genomics and computational approaches to map crosstalk between hepatocytes and liver macrophages during fasting. We identified the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome including fasting-suppressed cytokines and showed that lack of macrophage GR impaired induction of ketogenesis during fasting as well as endotoxemia. Mechanistically, macrophage GR suppressed the expression of tumor necrosis factor (TNF) and promoted nuclear translocation of hepatocyte GR to activate a fat oxidation/ketogenesis-related gene program, cooperatively induced by GR and peroxisome proliferator-activated receptor alpha (PPARα) in hepatocytes. Together, our results demonstrate how resident liver macrophages directly influence ketogenesis in hepatocytes, thereby also outlining a strategy by which the immune system can set the metabolic tone during inflammatory disease and infection.}, } @article {pmid35119530, year = {2022}, author = {Okines, A and Irfan, T and Asare, B and Mohammed, K and Osin, P and Nerurkar, A and Smith, IE and Parton, M and Ring, A and Johnston, S and Turner, NC}, title = {Clinical outcomes in patients with triple negative or HER2 positive lobular breast cancer: a single institution experience.}, journal = {Breast cancer research and treatment}, volume = {192}, number = {3}, pages = {563-571}, pmid = {35119530}, issn = {1573-7217}, mesh = {*Breast Neoplasms/drug therapy/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/metabolism ; Female ; Humans ; Neoplasm Recurrence, Local ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular carcinomas (ILC) are characterised by loss of the cell adhesion molecule E-cadherin. Approximately 15% of ILC are ER negative at the time of breast cancer diagnosis, or at relapse due to loss of ER expression. Less than 5% of classical ILC but up to 35% of pleomorphic ILC are HER2 positive (HER2+).

METHODS: Retrospective analysis of clinic-pathological data from patients with Triple negative (TN) or HER2+ ILC diagnosed 2004-2014 at the Royal Marsden Hospital. The primary endpoint was median overall survival (OS) in patients with metastatic disease. Secondary endpoints included response rate to neo-adjuvant chemotherapy (NAC), median disease-free interval (DFI) and OS for patients with early disease.

RESULTS: Three of 16 patients with early TN ILC and 7/33 with early HER2+ ILC received NAC with pCR rates of 0/3 and 3/5 patients who underwent surgery, respectively. Median DFI was 28.5 months [95% Confidence interval (95%CI) 15-78.8] for TN ILC and not reached (NR) (111.2-NR) for HER2+ early ILC. Five-year OS was 52% (95%CI 23-74%) and 77% (95%CI 58-88%), respectively. Twenty-three patients with advanced TN ILC and 14 patients with advanced HER2+ ILC were identified. Median OS was 18.3 months (95%CI 13.0-32.8 months) and 30.4 months (95%CI 8.8-NR), respectively.

CONCLUSIONS: In our institution we report a high relapse rate after treatment for early TN ILC, but median OS from metastatic disease is similar to that expected from TN IDC. Outcomes for patients with advanced HER2+ ILC were less favourable than those expected for IDC, possibly reflecting incomplete exposure to anti-HER2 therapies.

CLINICAL TRIAL REGISTRATION: ROLo (ClinicalTrials.gov Identifier: NCT03620643), ROSALINE (ClinicalTrials.gov Identifier: NCT04551495).}, } @article {pmid35116565, year = {2021}, author = {Wang, J and Wang, X and Du, W and Guo, Y and Yang, X and Pan, J and Yin, L}, title = {Primary neuroendocrine carcinoma of the breast with markedly elevated alpha-fetoprotein: a case report.}, journal = {Translational cancer research}, volume = {10}, number = {5}, pages = {2503-2508}, pmid = {35116565}, issn = {2219-6803}, abstract = {Primary neuroendocrine carcinoma of the breast (PNECB) is a relatively rare subtype of breast cancer that has seldom been studied since its initial description. At present, the pathogenesis of the disease remains unknown, and there exit no specific clinical guidelines or specifications for its diagnosis and treatment. In addition, alpha-fetoprotein (AFP)-despite being a tumor marker-plays a small role in the diagnosis of breast cancer. Here, we explain the diagnosis and treatment of primary neuroendocrine (NE) breast carcinoma in a patient with a markedly elevated level of AFP. A 52-year-old woman visited our hospital, reporting she had palpated a nodule in her left breast 1 day before admission. After ultrasonographic detection of the hypoechoic lesion in her left breast-which was classified according to the Breast Imaging Reporting and Data System (BI-RADS) as grade 4C-and the abnormal enlargement of her left axillary lymph nodes, the patient was referred to our department as a case of malignant breast tumor. Meanwhile, the level of the tumor marker AFP was found to be over 1,210 ng/mL (0-7 ng/mL). And the patient had no past medical history of increased AFP, abnormal liver function, or gastrointestinal tumor. Analysis of the surgical specimens obtained from the left breast showed grade II invasive ductal carcinoma with NE differentiation. After discussion with a multidisciplinary team (MDT), according to the results of pathological and immunohistochemical examinations, the patient was diagnosed with PNECB. Due to axillary lymph node metastasis, she received combined chemotherapy with cyclophosphamide, epirubicin, and paclitaxel on postoperative day 13. Up to now, six cycles of chemotherapy have been successfully administered, with no evidence of adverse reactions. AFP levels were all above 1,210 ng/mL during chemotherapy. At the time of submission, the patient has been followed up for 10 months and there has been axillary lymph node metastasis, but no tumors in other parts have been found. Therefore, we think that the increase in AFP levels is related to the occurrence and poor prognosis of PNECB.}, } @article {pmid35116538, year = {2021}, author = {Sang, G and Pan, H and Lu, C and Sun, R and Zha, X and Wang, S and Zhu, D}, title = {Clinical features and prognostic factors of male breast cancer vs. female breast cancer.}, journal = {Translational cancer research}, volume = {10}, number = {5}, pages = {2199-2209}, pmid = {35116538}, issn = {2219-6803}, abstract = {BACKGROUND: To investigate the clinicopathological features and prognostic factors of male breast cancer (MBC) and female breast cancer (FBC) patients.

METHODS: A total of 90 MBC and 180 FBC patients were included in this retrospective study. The clinicopathological features, disease-free survival rate (DFSR), and overall survival rate (OSR) were compared between the two groups. Cox proportional hazard model was used to analyze the factors affecting the survival rates.

RESULTS: Most MBC were invasive ductal carcinoma (70/90, 77.8%) and luminal type (83/90, 92.2%), and were treated with modified radical mastectomy (78/90, 86.7%). Compared with women, there were more patients with one-set age of ≥70 years old, having family history of cancer, comorbid with underlying diseases in the male patients. They also had higher portion of patients at T3 and T4 stages. The rates of male patients receiving adjuvant radiotherapy, chemotherapy and endocrine therapy were lower (P<0.05) than female patients. OSR and DFSR were lower in the male patients than in the female patients (P<0.05). T stage, TNM stage, the status of progesterone receptor and endocrine therapy were independent prognostic factors for survival of MBC (P<0.05); TNM stage, chemotherapy or endocrine therapy were independent factors for survival of FBC (P<0.05).

CONCLUSIONS: Compared with FBC, MBC occurs later with more underlying diseases and lower survival rates. MBC is less active in adjuvant therapy and endocrine therapy. Since MBC has more luminal type, increased endocrine therapy may improve the survival.}, } @article {pmid35114136, year = {2022}, author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR}, title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.}, journal = {The lancet. Diabetes & endocrinology}, volume = {10}, number = {3}, pages = {221-230}, pmid = {35114136}, issn = {2213-8595}, support = {CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom ; RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.}, } @article {pmid35103835, year = {2022}, author = {Cai, M and McNamara, K and Yamazaki, Y and Harada, N and Miyashita, M and Tada, H and Ishida, T and Sasano, H}, title = {The role of mineralocorticoids and glucocorticoids under the impact of 11β-hydroxysteroid dehydrogenase in human breast lesions.}, journal = {Medical molecular morphology}, volume = {55}, number = {2}, pages = {110-122}, pmid = {35103835}, issn = {1860-1499}, mesh = {11-beta-Hydroxysteroid Dehydrogenases ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Female ; Glucocorticoids ; Humans ; Mineralocorticoids ; }, abstract = {We attempted to explore the possible involvement of the in situ availability of mineralocorticoids and mineralocorticoid receptor (MR) in the pathogenesis of mammary ductal carcinoma. We also explored their individual profiles among different subtypes of invasive ductal carcinomas of no special type (IDC-NST) by evaluating the status of MR, Glucocorticoid receptor (GR), and 11β hydroxysteroid dehydrogenase (HSD) 1/2 at each stage of the putative cascade of the mammary ductal proliferative disorders. In this study, IDC-NST, ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH), and non-pathological breast tissues were all evaluated by immunohistochemistry. MR was significantly lower in ADH than in DCIS or IDC-NST. 11βHSD2 was significantly lower in ADH than normal breast tissue and 11βHSD1 was significantly higher in DCIS than normal, ADH, or IDC-NST. MR in progesterone receptor (PR)-positive IDC-NST cases tended to be associated with the Ki-67 labeling index. Results of the present study demonstrated that the status of MR and GR in conjunction with the 11βHSDs was correlated with the development of low-grade proliferative disorders in mammary glands. In addition, the potential crosstalk between MR and PR could also influence cell proliferation of breast carcinoma cells but further investigations are required for clarification.}, } @article {pmid35097195, year = {2022}, author = {Parthasarathy, S and Lee, DH and Levitt, AH and Manavalan, A}, title = {Pituitary Metastasis Presenting With Central Diabetes Insipidus and Panhypopituitarism.}, journal = {AACE clinical case reports}, volume = {8}, number = {1}, pages = {15-18}, pmid = {35097195}, issn = {2376-0605}, abstract = {OBJECTIVE: We report a case of pituitary metastasis (PM) presenting with acute anterior and posterior pituitary dysfunction following a two-decade-long oncologic course marked by disease progression.

CASE REPORT: An elderly woman with a history of stage IIA invasive ductal carcinoma of the breast presented with confusion. Her laboratory evaluation was significant for panhypopituitarism and central diabetes insipidus, and magnetic resonance imaging findings were suggestive of PM. She was treated with hormone replacement, resulting in the reversal of her metabolic and cognitive derangements.

DISCUSSION: PM is a rare complication of advanced malignancy. Although several malignancies may spread to the pituitary, the most common are breast cancer in women and lung cancer in men. Unlike pituitary adenomas, which predominantly involve the anterior pituitary, PM has a predilection for the posterior lobe and infundibulum due to direct access via systemic circulation. The clinical presentation of PM depends on the size of the metastatic deposit and other structures involved in the vicinity of the sella. Magnetic resonance imaging with gadolinium is the gold standard for the evaluation of sellar masses. The diagnosis of PM involves a thorough history, physical examination, biochemical evaluation of the hypothalamic-pituitary axis, and imaging studies.

CONCLUSION: Metastatic involvement of the pituitary is a rare condition seen in <2% of resected pituitary masses. The clinical presentation is heterogeneous and can include headache, visual impairment, and panhypopituitarism. Unfortunately, the presence of PM portends a poor prognosis, and the median survival rate after diagnosis is 6 to 13.6 months.}, } @article {pmid35094669, year = {2022}, author = {Li, J and Luu, LDW and Wang, X and Cui, X and Huang, X and Fu, J and Zhu, X and Li, Z and Wang, Y and Tai, J}, title = {Metabolomic analysis reveals potential biomarkers and the underlying pathogenesis involved in Mycoplasma pneumoniae pneumonia.}, journal = {Emerging microbes & infections}, volume = {11}, number = {1}, pages = {593-605}, pmid = {35094669}, issn = {2222-1751}, mesh = {Biomarkers ; Humans ; Metabolomics ; *Mycoplasma pneumoniae ; *Pneumonia, Mycoplasma/diagnosis ; Reproducibility of Results ; }, abstract = {Although previous studies have reported the use of metabolomics for infectious diseases, little is known about the potential function of plasma metabolites in children infected with Mycoplasma pneumoniae (MP). Here, a combination of liquid chromatography-quadrupole time-of-flight mass spectrometry and random forest-based classification model was used to provide a broader range of applications in MP diagnosis. In the training cohort, plasma from 63 MP pneumonia children (MPPs), 37 healthy controls (HC) and 29 infectious disease controls (IDC) was collected. After multivariate analyses, 357 metabolites were identified to be differentially expressed among MPP, HC and IDC groups, and 3 metabolites (568.5661, 459.3493 and 411.3208) had high diagnostic values. In an independent cohort with 57 blinded subjects, samples were successfully classified into different groups, demonstrating the reliability of these biomarkers for distinguishing MPPs from controls. A metabolomic signature analysis identified major classes of glycerophospholipids, sphingolipids and fatty acyls were increased in MPPs. These markedly altered metabolites are mainly involved in glycerophospholipid and sphingolipid metabolism. As the ubiquitous building blocks of eukaryotic cell membranes, dysregulated lipid metabolism indicates damage of the cellular membrane and the activation of immunity in MPPs. Moreover, lipid metabolites, differentially expressed between severe and mild MPPs, were correlated with the markers of extrapulmonary complications, suggesting that they may be involved in MPP disease severity. These findings may offer new insights into biomarker selection and the pathogenesis of MPP in children.}, } @article {pmid35089237, year = {2022}, author = {}, title = {Neoadjuvant chemotherapy reduces the expression rates of ER, PR, HER2, Ki67, and P53 of invasive ductal carcinoma: Erratum.}, journal = {Medicine}, volume = {101}, number = {4}, pages = {e28714}, pmid = {35089237}, issn = {1536-5964}, } @article {pmid35082620, year = {2021}, author = {Kitahara, M and Hozumi, Y and Machinaga, M and Hayashi, Y}, title = {A Case of Triple-Negative Breast Cancer with Germline Pathogenic Variants in Both BRCA1 and BRCA2.}, journal = {Case reports in oncology}, volume = {14}, number = {3}, pages = {1645-1651}, pmid = {35082620}, issn = {1662-6575}, abstract = {We report a rare case of hereditary breast and ovarian cancer syndrome (HBOC) with pathogenic variants in both BRCA1 and BRCA2. The patient was a 78-year-old woman who visited the hospital after noticing a lump in her left breast 6 months before, which gradually increased in size. According to her family history, her maternal aunt developed breast cancer in her 40s. On palpation, a 4-cm large mass was palpated in the upper outer part of the left breast. A needle biopsy revealed invasive ductal carcinoma of the breast, which was negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The patient was diagnosed with cT2N0M0 stage IIA, and primary systemic treatment was planned. The patient developed drug-induced interstitial pneumonia after receiving paclitaxel. Although she recovered spontaneously, she did not wish to receive further chemotherapy, and thus surgery was performed. Four months after the surgery, the patient became aware of dyspnea. After a thorough examination, she was diagnosed with postoperative cancer recurrence of the left breast with multiple liver metastases, cancerous peritonitis, multiple bone metastases, and multiple lymph node metastases. Genetic testing was performed, and pathogenic variants were found in both BRAC1 and BRCA2. However, her condition worsened, and she died 8 months after the surgery. BRCA pathogenic variants had more advanced breast cancer on initial diagnosis and worse cancer-related outcomes. It is desirable to consider the optimal approach to the treatment of breast cancer in pathogenic variants. In elderly patients with triple-negative breast cancer, HBOC may be suspected, based on biomarkers and family history. It is important to provide information on genetic counseling, genetic testing, and effective treatment plans proactively.}, } @article {pmid35082277, year = {2022}, author = {Van Bavel, JJ and Cichocka, A and Capraro, V and Sjåstad, H and Nezlek, JB and Pavlović, T and Alfano, M and Gelfand, MJ and Azevedo, F and Birtel, MD and Cislak, A and Lockwood, PL and Ross, RM and Abts, K and Agadullina, E and Aruta, JJB and Besharati, SN and Bor, A and Choma, BL and Crabtree, CD and Cunningham, WA and De, K and Ejaz, W and Elbaek, CT and Findor, A and Flichtentrei, D and Franc, R and Gjoneska, B and Gruber, J and Gualda, E and Horiuchi, Y and Huynh, TLD and Ibanez, A and Imran, MA and Israelashvili, J and Jasko, K and Kantorowicz, J and Kantorowicz-Reznichenko, E and Krouwel, A and Laakasuo, M and Lamm, C and Leygue, C and Lin, MJ and Mansoor, MS and Marie, A and Mayiwar, L and Mazepus, H and McHugh, C and Minda, JP and Mitkidis, P and Olsson, A and Otterbring, T and Packer, DJ and Perry, A and Petersen, MB and Puthillam, A and Riaño-Moreno, JC and Rothmund, T and Santamaría-García, H and Schmid, PC and Stoyanov, D and Tewari, S and Todosijević, B and Tsakiris, M and Tung, HH and Umbreș, RG and Vanags, E and Vlasceanu, M and Vonasch, A and Yucel, M and Zhang, Y and Abad, M and Adler, E and Akrawi, N and Mdarhri, HA and Amara, H and Amodio, DM and Antazo, BG and Apps, M and Ay, FC and Ba, MH and Barbosa, S and Bastian, B and Berg, A and Bernal-Zárate, MP and Bernstein, M and Białek, M and Bilancini, E and Bogatyreva, N and Boncinelli, L and Booth, JE and Borau, S and Buchel, O and Cameron, CD and Carvalho, CF and Celadin, T and Cerami, C and Chalise, HN and Cheng, X and Cian, L and Cockcroft, K and Conway, J and Córdoba-Delgado, MA and Crespi, C and Crouzevialle, M and Cutler, J and Cypryańska, M and Dabrowska, J and Daniels, MA and Davis, VH and Dayley, PN and Delouvee, S and Denkovski, O and Dezecache, G and Dhaliwal, NA and Diato, AB and Di Paolo, R and Drosinou, M and Dulleck, U and Ekmanis, J and Ertan, AS and Etienne, TW and Farhana, HH and Farkhari, F and Farmer, H and Fenwick, A and Fidanovski, K and Flew, T and Fraser, S and Frempong, RB and Fugelsang, JA and Gale, J and Garcia-Navarro, EB and Garladinne, P and Ghajjou, O and Gkinopoulos, T and Gray, K and Griffin, SM and Gronfeldt, B and Gümren, M and Gurung, RL and Halperin, E and Harris, E and Herzon, V and Hruška, M and Huang, G and Hudecek, MFC and Isler, O and Jangard, S and Jørgensen, FJ and Kachanoff, F and Kahn, J and Dangol, AK and Keudel, O and Koppel, L and Koverola, M and Kubin, E and Kunnari, A and Kutiyski, Y and Laguna, O and Leota, J and Lermer, E and Levy, J and Levy, N and Li, C and Long, EU and Longoni, C and Maglić, M and McCashin, D and Metcalf, AL and Mikloušić, I and El Mimouni, S and Miura, A and Molina-Paredes, J and Monroy-Fonseca, C and Morales-Marente, E and Moreau, D and Muda, R and Myer, A and Nash, K and Nesh-Nash, T and Nitschke, JP and Nurse, MS and Ohtsubo, Y and Oldemburgo de Mello, V and O'Madagain, C and Onderco, M and Palacios-Galvez, MS and Palomäki, J and Pan, Y and Papp, Z and Pärnamets, P and Paruzel-Czachura, M and Pavlović, Z and Payán-Gómez, C and Perander, S and Pitman, MM and Prasad, R and Pyrkosz-Pacyna, J and Rathje, S and Raza, A and Rêgo, GG and Rhee, K and Robertson, CE and Rodríguez-Pascual, I and Saikkonen, T and Salvador-Ginez, O and Sampaio, WM and Santi, GC and Santiago-Tovar, N and Savage, D and Scheffer, JA and Schönegger, P and Schultner, DT and Schutte, EM and Scott, A and Sharma, M and Sharma, P and Skali, A and Stadelmann, D and Stafford, CA and Stanojević, D and Stefaniak, A and Sternisko, A and Stoica, A and Stoyanova, KK and Strickland, B and Sundvall, J and Thomas, JP and Tinghög, G and Torgler, B and Traast, IJ and Tucciarelli, R and Tyrala, M and Ungson, ND and Uysal, MS and Van Lange, PAM and van Prooijen, JW and van Rooy, D and Västfjäll, D and Verkoeijen, P and Vieira, JB and von Sikorski, C and Walker, AC and Watermeyer, J and Wetter, E and Whillans, A and Willardt, R and Wohl, MJA and Wójcik, AD and Wu, K and Yamada, Y and Yilmaz, O and Yogeeswaran, K and Ziemer, CT and Zwaan, RA and Boggio, PS}, title = {National identity predicts public health support during a global pandemic.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {517}, pmid = {35082277}, issn = {2041-1723}, support = {I 3381/FWF_/Austrian Science Fund FWF/Austria ; MR/P014097/1/MRC_/Medical Research Council/United Kingdom ; MR/P014097/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/epidemiology/prevention & control/psychology ; Cross-Cultural Comparison ; Health Behavior ; Humans ; Leadership ; Pandemics/*legislation & jurisprudence/prevention & control/statistics & numerical data ; Public Health/*legislation & jurisprudence ; SARS-CoV-2 ; Self Report ; *Social Conformity ; Social Identification ; }, abstract = {Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.}, } @article {pmid35077053, year = {2022}, author = {Yariv, O and Benouaich-Amiel, A and Kab, T and Yust-Katz, S and Yerushalmi, R and Goldvaser, H}, title = {[RAPIDLY PROGRESSING PARAPARESIS AND LOSS OF SENSATION BELOW T10 DURING NEOADJUVANT CHEMOTHERAPY FOR BREAST CANCER].}, journal = {Harefuah}, volume = {161}, number = {1}, pages = {14-16}, pmid = {35077053}, issn = {0017-7768}, mesh = {Adult ; *Breast Neoplasms/diagnosis/drug therapy ; Female ; *Guillain-Barre Syndrome ; Humans ; Neoadjuvant Therapy ; Paraparesis ; Sensation ; }, abstract = {A 35 years old woman was diagnosed with clinical stage 2, grade 3, hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative invasive ductal carcinoma, with ki-67 of 60%. She was treated with neoadjuvant chemotherapy with dose dense adriamycin and cyclophosphamide followed by paclitaxel. Six days following the third cycle of paclitaxel the patient presented with rapidly progressive weakness, proximal paresthesia and decreased sensation in both legs. Physical examination revealed hypoesthesia below level, proximal and distal weakness in both lower limbs and absence of reflexes. MRI of the spine demonstrated diffuse leptomeningeal enhancement from T11 to S1 including the cauda equina roots. The rapidly progressive neurological symptoms and the MRI findings were initially interpreted as leptomeningeal spread. High dose dexamethasone was promptly initiated and the patient was urgently planned for radiotherapy and received the first fraction of 3 Gy to level T11-S1. Further workup included lumbar puncture which showed elevated protein level (350 mg/dL), negative cytology for malignancy and EMG which demonstrated demyelinating injury compatible with Guillain-Barre syndrome (GBS). A diagnosis of GBS was made and treatment with intravenous immunoglobulins (IVIG) was initiated, followed by a gradual clinical improvement. Two months after the initial diagnosis, she had a near complete resolution of her neurological deficits. This case illustrates both the tendency to ascribe new symptoms and clinical findings in cancer patients to progressive disease, and the importance of keeping a wide differential diagnosis for non-cancer etiologies when treating our patients.}, } @article {pmid35076741, year = {2022}, author = {Kanavati, F and Ichihara, S and Tsuneki, M}, title = {A deep learning model for breast ductal carcinoma in situ classification in whole slide images.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {480}, number = {5}, pages = {1009-1022}, pmid = {35076741}, issn = {1432-2307}, mesh = {Area Under Curve ; Biopsy ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/diagnosis ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; *Deep Learning ; Female ; Humans ; Pathologists ; }, abstract = {The pathological differential diagnosis between breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) is of pivotal importance for determining optimum cancer treatment(s) and clinical outcomes. Since conventional diagnosis by pathologists using microscopes is limited in terms of human resources, it is necessary to develop new techniques that can rapidly and accurately diagnose large numbers of histopathological specimens. Computational pathology tools which can assist pathologists in detecting and classifying DCIS and IDC from whole slide images (WSIs) would be of great benefit for routine pathological diagnosis. In this paper, we trained deep learning models capable of classifying biopsy and surgical histopathological WSIs into DCIS, IDC, and benign. We evaluated the models on two independent test sets (n= 1382, n= 548), achieving ROC areas under the curves (AUCs) up to 0.960 and 0.977 for DCIS and IDC, respectively.}, } @article {pmid35074971, year = {2022}, author = {Kumari, S and Mishra, S and Husain, N and Verma, T and Tiwari, V and Kaif, M and Agarwal, A and Rastogi, M and Shukla, S and Sonkar, AA}, title = {Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.}, journal = {Indian journal of pathology & microbiology}, volume = {65}, number = {1}, pages = {93-99}, doi = {10.4103/IJPM.IJPM_474_20}, pmid = {35074971}, issn = {0974-5130}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/genetics ; Brain Neoplasms/blood/diagnosis/genetics ; Carcinoma, Squamous Cell/blood/diagnosis/genetics ; Cell-Free Nucleic Acids/*blood ; Female ; Gallbladder Neoplasms/blood/diagnosis/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/blood/classification/*diagnosis/*genetics ; Young Adult ; }, abstract = {CONTEXT: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage.

DESIGN: Serum samples were collected from treatment naïve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis.

RESULTS: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases.

CONCLUSION: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.}, } @article {pmid35071526, year = {2022}, author = {Wang, L and Jiang, Q and He, MY and Shen, P}, title = {HER2 changes to positive after neoadjuvant chemotherapy in breast cancer: A case report and literature review.}, journal = {World journal of clinical cases}, volume = {10}, number = {1}, pages = {260-267}, pmid = {35071526}, issn = {2307-8960}, abstract = {BACKGROUND: As the most common cancer in women, breast cancer is the leading cause of death. Most patients are initially diagnosed as stage I-III. Among those without distant metastases, 64% are local tumors and 27% are regional tumors. Patients in stage IIA-IIIC and those who meet the breast-conserving criterion with the exception of tumor size can consider neoadjuvant chemotherapy (NACT). It is worth noting that the status of tumor cell biomarkers is not consistently static. Endocrine-related estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) encoded by erythroblastic leukemia viral oncogene homolog 2 gene can all alter from positive to negative or vice versa, especially in luminal B subtype after NACT. In addition, determination of HER2 status currently mainly relies on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), but FISH is commonly used when the result of IHC is uncertain. HER2 is regarded as negative when the IHC result is 0/1+ without the addition of FISH. To the best of our knowledge, this is the first report of a case harboring HER2 status transformation and IHC1+ with positive amplification by FISH after NACT.

CASE SUMMARY: A 49-year-old woman discovered a mass in her right breast and underwent diagnostic workup. Biopsies of the right breast lesion and axillary lymph nodes were obtained. The results pointed to invasive ductal carcinoma with the IHC result for ER (80%), PR (60%), Ki-67 (20%) and ambiguous expression of HER2 (IHC 2+) with negative amplification by FISH (HER2/CEP17 ratio of 1.13). She underwent surgery after NACT. The pathological findings of the surgically resected sample supported invasive ductal carcinoma with the tumor measuring 1.1 cm × 0.8 cm × 0.5 cm and had spread to one of fifteen dissected lymph nodes. Retesting of the specimen showed that the tumor was positive for ER (2+, 85%) and PR (2+, 10%) but negative for HER2 by IHC (1+). Also Ki-67 had dropped to 2%. The patient was regularly monitored every 3 mo without evidence of recurrence.

CONCLUSION: Biomarker status should be reassessed after NACT especially in luminal subtypes.}, } @article {pmid35070628, year = {2022}, author = {Sun, S and Li, J and Song, H and Chen, D and Tu, M and Chen, Q and Jiang, G and Zhou, Z}, title = {Comparative transcriptome and physiological analyses reveal key factors in the tolerance of peach rootstocks to iron deficiency chlorosis.}, journal = {3 Biotech}, volume = {12}, number = {1}, pages = {38}, pmid = {35070628}, issn = {2190-572X}, abstract = {UNLABELLED: Iron (Fe) deficiency chlorosis (IDC) is a major nutritional disorder in fruit trees grown on calcareous soils. As a peach rootstock, 'GF677' (Prunus dulcis Miller × P. persica (L.) Batsch) has great tolerance to Fe deficiency, but the molecular mechanisms of 'GF677' that support the process of iron deficiency chlorosis tolerance are still unknown. In this study, the key factors for differential iron deficiency chlorosis tolerance in two contrasting rootstocks (IDC-tolerant: 'GF677', IDC-susceptible: 'Maotao' (P. persica)) were investigated. 'GF677' exhibited greater Fe transfer and accumulation capacities when compared with 'Maotao', and the analysis of photosynthetic pigments, related precursors, and antioxidative enzyme activities further demonstrated that 'GF677' was more tolerant to IDC when compared with 'Maotao'. Furthermore, comparative transcriptome analysis revealed differential expression in many genes involved in iron transport and storage, and in photosynthesis recovery. These results suggest that the greater IDC tolerance of 'GF677' can be attributed to the greater expression of key genes related to specific Fe transporters, defense systems, photosynthetic recovery, and/or special proteins.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03046-6.}, } @article {pmid35064153, year = {2022}, author = {Tewari, SG and Kwan, B and Elahi, R and Rajaram, K and Reifman, J and Prigge, ST and Vaidya, AB and Wallqvist, A}, title = {Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {1167}, pmid = {35064153}, issn = {2045-2322}, support = {T32 AI138953/AI/NIAID NIH HHS/United States ; R01 AI154499/AI/NIAID NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command (MRDC)/ ; R01 AI132508/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; R01AI125534//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; W81XWH-20-C-0031//U.S. Army Medical Research and Development Command (MRDC)/ ; R01 AI098413/AI/NIAID NIH HHS/United States ; W81XWH-14-2-0134//U.S. Army Medical Research and Development Command (MRDC)/ ; }, mesh = {Antimalarials/*pharmacology/therapeutic use ; Carbohydrate Metabolism/drug effects/genetics ; Dose-Response Relationship, Drug ; Drug Resistance ; Erythrocytes/parasitology ; Gene Expression Profiling ; Humans ; Inositol/biosynthesis ; Malaria, Falciparum/*drug therapy/parasitology ; Metabolomics ; Oxidative Stress ; Plasmodium falciparum/*drug effects/genetics/metabolism ; Pyrazoles/*pharmacology/therapeutic use ; RNA, Protozoan/biosynthesis ; }, abstract = {Due to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol-a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.}, } @article {pmid35060538, year = {2022}, author = {Kim, YS and Lee, SE and Chang, JM and Kim, SY and Bae, YK}, title = {Ultrasonographic morphological characteristics determined using a deep learning-based computer-aided diagnostic system of breast cancer.}, journal = {Medicine}, volume = {101}, number = {3}, pages = {e28621}, pmid = {35060538}, issn = {1536-5964}, support = {06-2018-0030//Research fund of Samsung Medison, Seoul National University Hospital/ ; NRF-2021R1G1A1007686//National Research Foundation of Korea/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Computers ; *Deep Learning ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Ultrasonography/*methods ; }, abstract = {To investigate the correlations between ultrasonographic morphological characteristics quantitatively assessed using a deep learning-based computer-aided diagnostic system (DL-CAD) and histopathologic features of breast cancer.This retrospective study included 282 women with invasive breast cancer (<5 cm; mean age, 54.4 [range, 29-85] years) who underwent surgery between February 2016 and April 2017. The morphological characteristics of breast cancer on B-mode ultrasonography were analyzed using DL-CAD, and quantitative scores (0-1) were obtained. Associations between quantitative scores and tumor histologic type, grade, size, subtype, and lymph node status were compared.Two-hundred and thirty-six (83.7%) tumors were invasive ductal carcinoma, 18 (6.4%) invasive lobular carcinoma, and 28 (9.9%) micropapillary, apocrine, and mucinous. The mean size was 1.8 ± 1.0 (standard deviation) cm, and 108 (38.3%) cases were node positive. Irregular shape score was associated with tumor size (P < .001), lymph nodes status (P = .001), and estrogen receptor status (P = .016). Not-circumscribed margin (P < .001) and hypoechogenicity (P = .003) scores correlated with tumor size, and non-parallel orientation score correlated with histologic grade (P = .024). Luminal A tumors exhibited more irregular features (P = .048) with no parallel orientation (P = .002), whereas triple-negative breast cancer showed a rounder/more oval and parallel orientation.Quantitative morphological characteristics of breast cancers determined using DL-CAD correlated with histopathologic features and could provide useful information about breast cancer phenotypes.}, } @article {pmid35059584, year = {2022}, author = {Friedman-Eldar, O and Melnikau, S and Tjendra, Y and Avisar, E}, title = {Axillary Reverse Lymphatic Mapping in the Treatment of Axillary Accessory Breast Cancer: A Case Report and Review of Management.}, journal = {European journal of breast health}, volume = {18}, number = {1}, pages = {1-5}, pmid = {35059584}, issn = {2587-0831}, abstract = {Accessory breast tissue is a rare aberration of normal breast development, that presents most commonly in the axilla. Similar to normal breast tissue, it can undergo physiologic and pathologic changes, including malignant transformation. We report a rare case of accessory breast cancer, treated with surgical resection and axillary reverse mapping (ARM), and review current literature focusing on management. We report a 68-year-old female with a history of left breast cancer treated with lumpectomy and axillary dissection, who later developed in-breast recurrence treated with re-lumpectomy and sentinel node biopsy which mapped at the contralateral (right) axilla, but was negative. Two years later screening imaging revealed right axillary tail focal asymmetry with two spiculated masses. Core biopsy showed invasive ductal carcinoma (IDC), and histologic examination of the biopsy could not determine whether this represents a new primary breast cancer or axillary metastasis from the contralateral site. She underwent lumpectomy of the two masses and sentinel node biopsy. During surgery, the masses were identified in the axilla itself, rather than the axillary tail. Final pathology revealed IDC, pT1N0(sn), and extensive ductal carcinoma in situ (DCIS). Due to positive margins, she underwent re-lumpectomy with ARM. Final pathology revealed residual DCIS with negative new margins. The patient was referred for adjuvant radiotherapy. Accessory axillary breast tissue can be confused with axillary tail tissue. It is necessary for the surgeon to distinguish between them by meticulous physical examination and radiologic evaluation, as resection of axillary breast tissue may warrant reverse lymphatic mapping for lymphedema prevention.}, } @article {pmid35058312, year = {2022}, author = {Carlson, AL and Daniel, TD and DeSantis, A and Jabbour, S and Karslioglu French, E and Kruger, D and Miller, E and Ozer, K and Elliott, T}, title = {Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.}, journal = {BMJ open diabetes research & care}, volume = {10}, number = {1}, pages = {}, pmid = {35058312}, issn = {2052-4897}, mesh = {Adult ; Blood Glucose ; *Blood Glucose Self-Monitoring ; Canada/epidemiology ; *Diabetes Mellitus, Type 2/drug therapy ; Humans ; Insulin/therapeutic use ; Retrospective Studies ; United States/epidemiology ; }, abstract = {INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin.

RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort.

RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I[2]=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth.

CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.}, } @article {pmid35056420, year = {2022}, author = {Nakagawa, T and Oda, G and Mori, H and Uemura, N and Onishi, I and Sagawa, N and Fujioka, T and Mori, M and Kubota, K and Ishikawa, T and Okamoto, K and Uetake, H}, title = {Prognosis of Subcutaneous Mastectomy for Special Types of Breast Cancer.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {1}, pages = {}, pmid = {35056420}, issn = {1648-9144}, mesh = {*Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; *Mastectomy, Subcutaneous ; Prognosis ; Surgical Flaps ; }, abstract = {Background and objectives: In the treatment of the special type of breast cancer (STBC), the choice of chemotherapeutic agents is often based on the characteristic features of the histological type. On the other hand, the surgical strategy is usually determined by the tumor size and presence of lymph node metastasis, and the indication for immediate reconstruction is rarely discussed based on the histological type. The prognoses of STBC and invasive ductal carcinoma of the breast (IDC) patients who underwent subcutaneous mastectomy (SCM) with immediate reconstruction at our institution were compared. Materials and Methods: A total of 254 patients with SCM with immediate reconstruction from 1998 to 2018 were included; their tumor diameter or induration was less than 25 mm, and it was not in close proximity to the skin. Preoperative chemotherapy and non-invasive cancer cases were excluded. Results: The number of patients was 166 for skin-sparing mastectomy (SSM) and 88 for nipple-sparing mastectomy (NSM). The reconstructive techniques were deep inferior epigastric artery perforator flap (DIEP) reconstruction in 43 cases, latissimus dorsi flap reconstruction (LDflap) in 63 cases, tissue expander (TE) in 117 cases, and transverse rectus abdominis myocutaneous flap/vertical rectus abdominis myocutaneous flap (TRAM/VRAM) reconstruction in 31 cases. The histological types of breast cancer were 211 IDC and 43 STBC; 17 were mucinous carcinoma (MUC), 17 were invasive lobular carcinoma (ILC), 6 were apocrine carcinoma, 1 was tubular carcinoma, and 2 were invasive micropapillary carcinoma. There was no difference in local recurrence or disease-free survival (LRFS, DFS) between IDC and STBC, and overall survival (OS) was significantly longer in STBC. OS was better in the STBC group because SCM with immediate reconstruction was performed for STBC, which is a histological type with a relatively good prognosis. Highly malignant histological types, such as squamous cell carcinoma or metaplastic carcinoma, were totally absent in this study. Conclusions: The indications for SCM with immediate reconstruction for relatively common STBCs such as MUC and ILC can be the same as for IDC.}, } @article {pmid35054193, year = {2021}, author = {Adachi, M and Nakagawa, T and Fujioka, T and Mori, M and Kubota, K and Oda, G and Kikkawa, T}, title = {Feasibility of Portable Microwave Imaging Device for Breast Cancer Detection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054193}, issn = {2075-4418}, abstract = {PURPOSE: Microwave radar-based breast imaging technology utilizes the principle of radar, in which radio waves reflect at the interface between target and normal tissues, which have different permittivities. This study aims to investigate the feasibility and safety of a portable microwave breast imaging device in clinical practice.

MATERIALS AND METHODS: We retrospectively collected the imaging data of ten breast cancers in nine women (median age: 66.0 years; range: 37-78 years) who had undergone microwave imaging examination before surgery. All were Japanese and the tumor sizes were from 4 to 10 cm. Using a five-point scale (1 = very poor; 2 = poor; 3 = fair; 4 = good; and 5 = excellent), a radiologist specialized in breast imaging evaluated the ability of microwave imaging to detect breast cancer and delineate its location and size in comparison with conventional mammography and the pathological findings.

RESULTS: Microwave imaging detected 10/10 pathologically proven breast cancers, including non-invasive ductal carcinoma in situ (DCIS) and micro-invasive carcinoma, whereas mammography failed to detect 2/10 breast cancers due to dense breast tissue. In the five-point evaluation, median score of location and size were 4.5 and 4.0, respectively.

CONCLUSION: The results of the evaluation suggest that the microwave imaging device is a safe examination that can be used repeatedly and has the potential to be useful in detecting breast cancer.}, } @article {pmid35051228, year = {2022}, author = {Kwon, D and Ko, BK and Jung, SP and Kim, HK and Kim, EK and Jung, YS and Youn, HJ and Lee, SB}, title = {Survival analysis in patients with invasive lobular cancer and invasive ductal cancer according to hormone receptor expression status in the Korean population.}, journal = {PloS one}, volume = {17}, number = {1}, pages = {e0262709}, pmid = {35051228}, issn = {1932-6203}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/metabolism/*mortality/pathology ; Carcinoma, Lobular/metabolism/*mortality/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Republic of Korea/epidemiology ; Survival Analysis ; Survival Rate ; }, abstract = {BACKGROUND: We compared the clinicopathological characteristics and survival outcomes of invasive lobular carcinoma (ILC) cases with those of invasive ductal carcinoma (IDC) cases in various hormone receptor expression subgroups.

METHODS: We compared clinicopathological characteristics, overall survival (OS), and breast cancer-specific survival (BCSS) between patients with IDC (n = 95,486) and ILC (n = 3,023). In addition, we analyzed the effects of different hormone receptor expression subgroups on survival.

RESULTS: The ILC group had more instances of advanced stage and hormonal receptor positivity than did the IDC group (p < 0.001), but the IDC group had higher histological grade and nuclear grade, as well as higher frequency of human epidermal growth factor receptor 2 and Ki67 expression than did the ILC group (p < 0.001). The OS and BCSS were not significantly different between the IDC and ILC groups. The 5-year OS of the IDC group was 88.8%, while that of the ILC group was 90.6% (p = 0.113). The 5-year BCSS of the IDC group was 94.8%, while that of the ILC group was 95.0% (p = 0.552). When analyzing each hormone receptor expression subgroup, there were no significant differences in survival between the IDC and ILC groups. However, the estrogen receptor (ER) negative/progesterone receptor (PR) negative subgroup showed differences in survival between the IDC and ILC groups. Moreover, the hazard ratio of ILC in the ER negative/PR negative subgroup was 1.345 (95% confidence interval: 1.012-1.788; p = 0.041).

CONCLUSIONS: Hormone receptor expression should be considered when determining prognosis and treatment regimen for IDC and ILC. Researchers should further study the ER negative/PR negative population to identify treatment and prognostic models that will facilitate the development of individualized therapy for these patients, which is needed for good outcomes.}, } @article {pmid35050415, year = {2022}, author = {Zhang, J and Wang, G and Ren, J and Yang, Z and Li, D and Cui, Y and Yang, X}, title = {Multiparametric MRI-based radiomics nomogram for preoperative prediction of lymphovascular invasion and clinical outcomes in patients with breast invasive ductal carcinoma.}, journal = {European radiology}, volume = {32}, number = {6}, pages = {4079-4089}, pmid = {35050415}, issn = {1432-1084}, support = {82001789//national natural science foundation of china/ ; 81802479//national natural science foundation of china/ ; 2019058//youth project of shanxi provincial health commission/ ; 2020-MS01//open fund from shanxi medical university-collaborative innovation center for molecular imaging of precision medicine/ ; 201801D121307//applied basic research programs of shanxi province/ ; 201801D221390//applied basic research programs of shanxi province/ ; 82171923//National Natural Science Foundation of China/ ; }, mesh = {*Carcinoma, Ductal ; Humans ; Magnetic Resonance Imaging/methods ; *Multiparametric Magnetic Resonance Imaging ; Nomograms ; Retrospective Studies ; }, abstract = {OBJECTIVE: To develop a multiparametric MRI-based radiomics nomogram for predicting lymphovascular invasion (LVI) status and clinical outcomes in patients with breast invasive ductal carcinoma (IDC).

METHODS: A total of 160 patients with pathologically confirmed breast IDC (training cohort: n = 112; validation cohort: n = 48) who underwent preoperative breast MRI were included. Imaging features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted imaging (cT1WI) sequences. A four-step procedure was applied for feature selection and radiomics signature building. Univariate and multivariate logistic regression analyses were conducted to identify the features associated with LVI, which were then incorporated into the radiomics nomogram. The performance of the nomogram was evaluated by its discrimination, calibration, and clinical usefulness. Kaplan-Meier survival curves based on the two radiomics models were used to estimate disease-free survival (DFS).

RESULTS: The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. The proposed radiomics nomogram, incorporating the fusion radiomics signature and MRI-reported peritumoral edema, showed satisfactory capabilities of calibration and discrimination in both training and validation datasets, with AUCs of 0.919 (95% CI: 0.871-0.967) and 0.863 (95% CI: 0.726-0.999), respectively. The radiomics signature and nomogram-defined high-risk groups had a shorter DFS than those in the low-risk groups (both p < 0.05). Higher Rad-scores were independently associated with a worse DFS in the whole cohort (p < 0.05).

CONCLUSIONS: The proposed nomogram, incorporating multiparametric MRI-based radiomics signature and MRI-reported peritumoral edema, achieved a satisfactory preoperative prediction of LVI and clinical outcomes in IDC patients.

KEY POINTS: • The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. • The proposed nomogram achieved a favorable prediction of LVI in IDC patients with AUCs of 0.919 and 0.863 in the training and validation datasets, respectively. • The radiomics model could classify patients into high- and low-risk groups with significant differences in DFS.}, } @article {pmid35047160, year = {2022}, author = {Jiang, M and Lei, S and Zhang, J and Hou, L and Zhang, M and Luo, Y}, title = {Multimodal Imaging of Target Detection Algorithm under Artificial Intelligence in the Diagnosis of Early Breast Cancer.}, journal = {Journal of healthcare engineering}, volume = {2022}, number = {}, pages = {9322937}, pmid = {35047160}, issn = {2040-2309}, mesh = {Algorithms ; *Artificial Intelligence ; Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging/pathology ; Female ; Humans ; Male ; Multimodal Imaging ; }, abstract = {This study aimed to analyze the diagnostic value of multimodal images based on artificial intelligence target detection algorithms for early breast cancer, so as to provide help for clinical imaging examinations of breast cancer. This article combined residual block with inception block, constructed a new target detection algorithm to detect breast lumps, used deep convolutional neural network and ultrasound imaging in diagnosing benign and malignant breast lumps, took breast density grading with mammography, compared the convolutional neural network (CNN) algorithm with the proposed algorithm, and then applied the proposed algorithm to the diagnosis of 120 female patients with breast lumps. According to the results, accuracy rates of breast lump detection (94.76%), benign and malignant breast lumps diagnosis (98.22%), and breast grading (93.65%) with the algorithm applied in this study were significantly higher than those (75.67%, 87.23%, and 79.54%) with CNN algorithm, and the difference was statistically significant (P < 0.05); among 62 patients with malignant breast lumps of the 120 patients with breast lumps, 37 were patients with invasive ductal carcinoma, 8 with lobular carcinoma in situ, 16 with intraductal carcinoma, and 4 with mucinous carcinoma; among the remaining 58 patients with benign breast lumps, 28 were patients with fibrocystic breast disease, 17 with intraductal papilloma, 4 with breast hyperplasia, and 9 with adenopathy; the differences in shape, growth direction, edge, and internal echo of multimodal ultrasound imaging of patients with benign and malignant breast lumps had statistical significance (P < 0.05); the malignant constituent ratios of patients with breast density grades I to IV were 0%, 7.10%, 80.40%, and 100%, respectively. In short, the multimodal imaging diagnosis under the algorithm in this article was superior to CNN algorithm in all aspects; according to the judgment on benign and malignant breast lumps and breast density with multimodal imaging features, the higher the breast density, the higher the probability of breast cancer.}, } @article {pmid35046349, year = {2021}, author = {Adachi, K and Kubota, H and Suzuki, S and Hirano, T and Ishibashi, N and Sakurai, K}, title = {[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {1843-1845}, pmid = {35046349}, issn = {0385-0684}, mesh = {Adult ; Axilla ; *Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Nodes ; Mastectomy ; *Ovarian Neoplasms/genetics/surgery ; }, abstract = {We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.}, } @article {pmid35046335, year = {2021}, author = {Yanai, A and Nishino, M and Kojima, S and Yamasaki, J and Uda, Y and Ohara, S and Hamada, T and Ohashi, K and Nakao, E and Murakami, M and Okada, T}, title = {[A Case of Breast Cancer in the Elderly Localized in the Nipple].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {1801-1803}, pmid = {35046335}, issn = {0385-0684}, mesh = {Aged, 80 and over ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Mammography ; Nipples/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {An 89-year-old woman presented to our clinic with a complaint of a wound in the left nipple. The pathological diagnosis via skin biopsy revealed adenocarcinoma. A physical examination, mammography, ultrasonography, and CT scan revealed a mass in the left nipple. However, a definite diagnosis could not be established by skin biopsy. Left breast-conserving surgery and sentinel lymph node biopsy were performed for diagnosis and treatment. Histological examination revealed a scirrhous type invasive ductal carcinoma in the left nipple and areola with skin invasion and lymph node metastasis. Radiation and hormone therapy were used as adjuvant therapy. She is alive with no local recurrence for 5 months post surgery. Since ductal carcinoma of the nipple is uncommon, we present this case report along with a review of the relevant literature.}, } @article {pmid35046283, year = {2021}, author = {Kawai, H and Imamura, Y and Kondoh, A and Mizuno, D and Suemori, K and Miyauchi, S and Iga, N and Yoshida, R and Uno, F and Ishizaki, M and Nishi, H and Yamashita, K and Miyohi, S}, title = {[A Case of Intraductal Apocrine Carcinoma of the Breast].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {1643-1645}, pmid = {35046283}, issn = {0385-0684}, mesh = {Breast ; *Breast Neoplasms/surgery ; *Carcinoma, Intraductal, Noninfiltrating/surgery ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; }, abstract = {A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.}, } @article {pmid35046255, year = {2021}, author = {Terakawa, H and Ogaito, T and Okamoto, K and Shima, S and Terasaki, K and Tanaka, H and Hashimoto, M and Zaimoku, R and Takei, R and Terada, I and Tsukioka, Y and Kiriyama, M}, title = {[Stage Ⅳ HER2-Positive Breast Cancer That Showed Complete Response for Over One Year after Discontinuation of Anti-HER2 Therapy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {1559-1560}, pmid = {35046255}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy ; Female ; Humans ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {A 75-year-old woman with a left breast mass on breast cancer screening was referred to our hospital for detailed evaluation. Further examination revealed left breast cancer with metastases to the left axilla, left parasternal region, left supraclavicular fossa, mediastinum, and left hilar lymph nodes, as well as multiple lung metastases. Histopathological evaluation of a needle biopsy specimen revealed invasive ductal carcinoma(scirrhous type), and she was diagnosed with Stage Ⅳ human epidermal growth factor receptor 2(HER2)-positive breast cancer. Following diagnosis, treatment was initiated with trastuzumab, pertuzumab, and docetaxel; however, she developed hypersensitivity to docetaxel and received only trastuzumab and pertuzumab after the second course. We observed a complete response after 3 courses, and treatment was discontinued after 13 courses. She underwent regular evaluation after treatment discontinuation, and a complete response was maintained for 1 year and 6 months. We conclude that combination therapy comprising trastuzumab and pertuzumab was effective for Stage Ⅳ HER2-positive breast cancer and that a complete response could be maintained even after treatment discontinuation.}, } @article {pmid35045506, year = {2021}, author = {Satoh, E and Yatabe, Y and Uehira, D and Yonekura, K and Murakata, A and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T and Maruyama, S}, title = {[A Case of Pyloric Stenosis Due to Gastric Metastasis of Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {2103-2105}, pmid = {35045506}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pyloric Stenosis ; }, abstract = {We report a case of left advanced breast cancer(T4N1M0, Stage ⅢA)in a 67-year-old woman. In August 2010, her breast cancer(triple-negative invasive ductal carcinoma)was resected(mastectomy plus axillary lymph node dissection) with adjuvant chemotherapy(TC)and irradiation to her chest wall. In July 2018, she experienced recurrent vomiting. Gastrointestinal endoscopy(GS)revealed type Ⅳ advanced gastric cancer-like appearance with pyloric stenosis. Pathological findings confirmed hormone-positive gastric metastasis of breast cancer. Systemic chemo-endocrine therapy(EC and anastrozole) was performed, following which her symptoms improved. In May 2019, recurrent vomiting appeared again. Thereafter, systemic chemo-endocrine therapy(paclitaxel plus bevacizumab and fulvestrant)was initiated, and her symptoms showed improvement. In November 2020, she showed obstructive jaundice due to malignant biliary stenosis. She was treated using endoscopic biliary stenting, but died 2 months later. Gastric metastasis is reported rarely in 4% of all breast cancers, and GS should be recommended in cases of recurrent abdominal complaints.}, } @article {pmid35045484, year = {2021}, author = {Goto, W and Nagamori, M and Yamakoshi, Y and Nomura, S and Takashima, T and Otani, H and Ohira, M}, title = {[A Case of Adenoid Cystic Carcinoma of the Breast].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {2033-2035}, pmid = {35045484}, issn = {0385-0684}, mesh = {Biopsy, Large-Core Needle ; *Breast Neoplasms/surgery ; *Carcinoma, Adenoid Cystic/diagnostic imaging/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {Primary adenoid cystic carcinoma(ACC)of the breast is a rare type of breast cancer. A 53-year-old woman with a right breast mass was examined at our institute. Ultrasonography showed 12.5×10.3×8.4 mm sized an ill-defined hypoechoic mass at zone C of the right breast. Pathological examination of core needle biopsy revealed atypical cells with solid and cribriform growth pattern. Computed tomography did not reveal lymph node metastases or distant metastases. The preoperative diagnosis was Stage ⅠA(cT1cN0M0, ER/PgR/HER2=-/-/1+)invasive ductal carcinoma or ACC. Surgery consisted of breast-conserving surgery and sentinel node biopsy. Pathological examination of the excised specimen revealed a so- called adenoid cystic pattern, so the final diagnosis was Stage ⅠA(pT1cN0M0, ER/PgR/HER2=-/-/1+)ACC. After 1 year of observation without adjuvant treatment, there has been no recurrence.}, } @article {pmid35045475, year = {2021}, author = {Nakanishi, K and Goto, W and Ishihara, A and Tauchi, J and Kashiwagi, S and Amano, R and Kubo, S and Ohira, M}, title = {[A Case of Synchronous Double Cancer including Borderline Resectable Pancreatic Body Cancer and Breast Carcinoma with Osseous/Cartilaginous Differentiation Treated with Neoadjuvant Chemotherapy and Radical Resection].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {2005-2007}, pmid = {35045475}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Mastectomy ; Neoadjuvant Therapy ; *Pancreatic Neoplasms/drug therapy/surgery ; }, abstract = {A 78-year-old woman with a left breast cancer was examined at our institute. Ultrasonography showed 48 mm sized mass at zone C of the left breast, and left axillary lymph node swelling. Pathological examination of core needle biopsy revealed invasive ductal carcinoma and lymph node metastasis. In addition, contrast computed tomography showed 30 mm sized an hypovascular mass at pancreatic body involved the portal vein. Endoscopic ultrasound guided fine needle aspiration biopsy of the pancreas revealed adenocarcinoma. The diagnosis was synchronous double cancer including borderline resectable pancreatic body cancer and left breast cancer, and she received neoadjuvant chemotherapy consisting of gemcitabine and nab-paclitaxel. The effect of neoadjuvant chemotherapy was judged to be stable disease for breast cancer, partial response for pancreatic cancer. Then, she underwent pancreatosplenectomy with portal vein and gastroduodenal artery resection and reconstruction, left mastectomy and axillary lymph node dissection. Pathologic examination of the excised specimen revealed the diagnosis of breast cancer with osseous/cartilaginous differentiation and pancreatic moderately differentiated adenocarcinoma. She was treated with fluorouracil, epirubicin, and cyclophosphamide as adjuvant therapy, and there has been no recurrence.}, } @article {pmid35045474, year = {2021}, author = {Otake, H and Takizawa, K and Nagaro, H and Toge, K and Hirose, Y and Ishikawa, H and Miura, K and Ichikawa, H and Hanyu, T and Nagahashi, M and Shimada, Y and Ishikawa, T and Sakata, J and Kobayashi, T and Wakai, T}, title = {[A Case of Long-Term Survival after Resection of Pancreatic Ductal Adenocarcinoma with Para-Aortic Lymph Node Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {2002-2004}, pmid = {35045474}, issn = {0385-0684}, mesh = {*Carcinoma, Pancreatic Ductal/drug therapy/surgery ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Middle Aged ; *Pancreatic Neoplasms/drug therapy/surgery ; Prognosis ; Retrospective Studies ; }, abstract = {The patient was a 64-year-old man with diagnosis of pancreatic head cancer. Initially, abdominal CT showed pancreatic head tumor with bile duct invasion and no distant metastases including para-aortic lymph nodes(PALN). Although, subtotal stomach-preserving pancreatoduodenectomy(SSPPD)and PALN sampling was performed, intraoperative frozen section examination revealed PALN metastasis. He had chronic kidney disease and was unsuitable for standard chemotherapy, SSPPD and PALN dissection was performed instead of standard chemotherapy. Histopathological examination of the resected specimens revealed invasive ductal carcinoma in the pancreatic head region and 11 nodes out of the 17 dissected PALN. Adjuvant chemotherapy with S-1 was performed. 22 months after surgery, intraabdominal lymph nodes metastasis and lung metastasis was found. 24 months after surgery, palliative radiation therapy at a dose of 40 Gy was performed. Systemic chemotherapy with gemcitabine alone was performed, but he was dead 67 months after the initial therapy.}, } @article {pmid35045436, year = {2021}, author = {Tojo, K and Abe, S and Tachibana, K and Hoshi, N and Murakami, Y and Noda, M and Ishigami, H and Soeda, S and Watanabe, N and Kiko, Y and Hashimoto, Y and Otake, T}, title = {[A Case Report of Uterine Metastasis Four Years after Breast Surgery for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {13}, pages = {1885-1888}, pmid = {35045436}, issn = {0385-0684}, mesh = {Breast ; *Breast Neoplasms/drug therapy/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Mastectomy ; Mastectomy, Segmental ; Sentinel Lymph Node Biopsy ; }, abstract = {We report a case of uterine metastasis of the breast cancer. The patient was diagnosed with invasive ductal carcinoma of the breast and underwent partial right mastectomy and sentinel lymph node biopsy. Tamoxifen was administered as adjuvant endocrine therapy. Four years after the surgery, she had irregular genital bleeding, and was referred to our hospital for cytological diagnosis of uterine cancer. Postoperative pathological diagnosis showed uterine metastasis of breast cancer, and it was decided to treat the recurrence of breast cancer with aromatase inhibitors and CDK4/6 inhibitors, a molecular targeted therapy. The patient has been progression-free for 5 months.}, } @article {pmid35039654, year = {2022}, author = {Imhoff, R and Zimmer, F and Klein, O and António, JHC and Babinska, M and Bangerter, A and Bilewicz, M and Blanuša, N and Bovan, K and Bužarovska, R and Cichocka, A and Delouvée, S and Douglas, KM and Dyrendal, A and Etienne, T and Gjoneska, B and Graf, S and Gualda, E and Hirschberger, G and Kende, A and Kutiyski, Y and Krekó, P and Krouwel, A and Mari, S and Đorđević, JM and Panasiti, MS and Pantazi, M and Petkovski, L and Porciello, G and Rabelo, A and Radu, RN and Sava, FA and Schepisi, M and Sutton, RM and Swami, V and Thórisdóttir, H and Turjačanin, V and Wagner-Egger, P and Žeželj, I and van Prooijen, JW}, title = {Conspiracy mentality and political orientation across 26 countries.}, journal = {Nature human behaviour}, volume = {6}, number = {3}, pages = {392-403}, pmid = {35039654}, issn = {2397-3374}, support = {20-01214S//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; }, abstract = {People differ in their general tendency to endorse conspiracy theories (that is, conspiracy mentality). Previous research yielded inconsistent findings on the relationship between conspiracy mentality and political orientation, showing a greater conspiracy mentality either among the political right (a linear relation) or amongst both the left and right extremes (a curvilinear relation). We revisited this relationship across two studies spanning 26 countries (combined N = 104,253) and found overall evidence for both linear and quadratic relations, albeit small and heterogeneous across countries. We also observed stronger support for conspiracy mentality among voters of opposition parties (that is, those deprived of political control). Nonetheless, the quadratic effect of political orientation remained significant when adjusting for political control deprivation. We conclude that conspiracy mentality is associated with extreme left- and especially extreme right-wing beliefs, and that this non-linear relation may be strengthened by, but is not reducible to, deprivation of political control.}, } @article {pmid35036180, year = {2021}, author = {Das Majumdar, SK and Das, DK and Barik, S and Badajena, A and Parida, DK}, title = {Evaluation of Clinicopathological and Prognostic Factors of Male Breast Cancer: A Single-Centre Experience.}, journal = {Cureus}, volume = {13}, number = {12}, pages = {e20298}, pmid = {35036180}, issn = {2168-8184}, abstract = {Male breast cancer (MBC) is a rare malignancy with an overall incidence of less than 1%. The epidemiological data of MBC is very limited owing to its rarity, particularly data from India. Hence, it is important to study different aspects of this rare malignancy. This paper reports a single-center experience from India that evaluated the clinicopathological behavior of MBC, their management, and outcomes. This was a retrospective review, which included 18 patients managed between 2013 to 2021. Seventeen out of the 18 patients were aged ≥50 years; the median age was 60 years. Left sides were affected more than right (left: 11, right: seven), and the most commonly affected quadrant was central (n=15/17, 88.2%). The most common (n=14) surgery was modified radical mastectomy (MRM), and the invasive ductal carcinoma was the most common (n=14) histological finding. Most cases were estrogen-receptor (ER) and progesterone-receptor-positive (n=15/18, 83.3%). The present study, though with a small sample size, adds valuable information to the literature about this rare occurrence in men.}, } @article {pmid35033452, year = {2022}, author = {Kim, MY and Suh, YJ and An, YY}, title = {Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection among Women with a History of Breast Cancer.}, journal = {Academic radiology}, volume = {29}, number = {10}, pages = {1458-1465}, doi = {10.1016/j.acra.2021.12.013}, pmid = {35033452}, issn = {1878-4046}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Early Detection of Cancer ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Mass Screening ; Middle Aged ; }, abstract = {RATIONALE AND OBJECTIVES: To compare the diagnostic performance of abbreviated breast MRI (AB-MRI) and digital breast tomosynthesis (DBT) in women with a personal history (PH) of breast cancer as a postoperative screening tool.

MATERIALS AND METHODS: A total of 471 patients who completed both DBT and AB-MRI examinations were included in this study (median age, 54.5 years). The detected cancer characteristics were analyzed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) were calculated by receiver operating characteristic (ROC) curve analysis.

RESULTS: Eleven malignancies were diagnosed, and most of the detected cancers were stage I (7 of 11, 63.6%). Eight were invasive ductal carcinomas (IDC), and 3 were ductal carcinoma in situ (DCIS). Of the 11 recurrences, 6 malignancies were detected by DBT, and 11 were detected by AB-MRI. AB-MRI detected all 8 IDC and 3 DCIS lesions, and DBT detected 6 of 8 IDC lesions. The CDRs for DBT and AB-MRI screenings were 12.7 and 23.4 per 1,000 women, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of DBT versus AB-MRI were 54.6% versus 100%, 97.6% versus 96.5%, 35.3% versus 40.7%, 98.9% versus 100%, and 96.6% versus 96.6%, respectively. AB-MRI showed a higher AUC value (0.983) than DBT (0.761) (p = 0.0049).

CONCLUSION: AB-MRI showed an improved CDR, especially for invasive cancer. The diagnostic performance of AB-MRI was superior to that of DBT with high sensitivity and PPV without sacrificing specificity in women with a PH of breast cancer.}, } @article {pmid35030551, year = {2022}, author = {Taitelbaum-Swead, R and Icht, M and Ben-David, BM}, title = {More Than Words: the Relative Roles of Prosody and Semantics in the Perception of Emotions in Spoken Language by Postlingual Cochlear Implant Users.}, journal = {Ear and hearing}, volume = {43}, number = {4}, pages = {1378-1389}, doi = {10.1097/AUD.0000000000001199}, pmid = {35030551}, issn = {1538-4667}, mesh = {Adolescent ; Adult ; Aged ; *Cochlear Implantation ; *Cochlear Implants ; Emotions ; Humans ; Language ; Middle Aged ; Semantics ; *Speech Perception ; Young Adult ; }, abstract = {OBJECTIVES: The processing of emotional speech calls for the perception and integration of semantic and prosodic cues. Although cochlear implants allow for significant auditory improvements, they are limited in the transmission of spectro-temporal fine-structure information that may not support the processing of voice pitch cues. The goal of the current study is to compare the performance of postlingual cochlear implant (CI) users and a matched control group on perception, selective attention, and integration of emotional semantics and prosody.

DESIGN: Fifteen CI users and 15 normal hearing (NH) peers (age range, 18-65 years) 1istened to spoken sentences composed of different combinations of four discrete emotions (anger, happiness, sadness, and neutrality) presented in prosodic and semantic channels-T-RES: Test for Rating Emotions in Speech. In three separate tasks, listeners were asked to attend to the sentence as a whole, thus integrating both speech channels (integration), or to focus on one channel only (rating of target emotion) and ignore the other (selective attention). Their task was to rate how much they agreed that the sentence conveyed each of the predefined emotions. In addition, all participants performed standard tests of speech perception.

RESULTS: When asked to focus on one channel, semantics or prosody, both groups rated emotions similarly with comparable levels of selective attention. When the task was called for channel integration, group differences were found. CI users appeared to use semantic emotional information more than did their NH peers. CI users assigned higher ratings than did their NH peers to sentences that did not present the target emotion, indicating some degree of confusion. In addition, for CI users, individual differences in speech comprehension over the phone and identification of intonation were significantly related to emotional semantic and prosodic ratings, respectively.

CONCLUSIONS: CI users and NH controls did not differ in perception of prosodic and semantic emotions and in auditory selective attention. However, when the task called for integration of prosody and semantics, CI users overused the semantic information (as compared with NH). We suggest that as CI users adopt diverse cue weighting strategies with device experience, their weighting of prosody and semantics differs from those used by NH. Finally, CI users may benefit from rehabilitation strategies that strengthen perception of prosodic information to better understand emotional speech.}, } @article {pmid35029184, year = {2022}, author = {Hussain, M and Abbott, M and Zargham, R and Pabani, A and Khan, OF}, title = {Evolution of an invasive ductal carcinoma to a small cell carcinoma of the breast: A case report.}, journal = {Medicine}, volume = {101}, number = {2}, pages = {e28433}, pmid = {35029184}, issn = {1536-5964}, mesh = {*Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; *Carcinoma, Small Cell/diagnosis/therapy ; Female ; Humans ; *Lymphadenopathy ; Middle Aged ; Retrospective Studies ; }, abstract = {RATIONALE: Small cell carcinoma (SCC) is a rare subtype of breast cancer and presents a complex diagnostic and treatment challenge, due to paucity of data. To the best of our knowledge, most cases of breast SCC reported in the literature describe a de novo breast primary. Our case is unique as it describes the evolution of an invasive ductal carcinoma after treatment into a SCC of the breast.

We report a case of a 53-year-old female, lifelong non-smoker, who initially presented with breast mass noted on self examination. Breast and axillary lymph node biopsy demonstrated a hormone receptor positive invasive ductal carcinoma with a metastatic T3 lesion.

INTERVENTION: She was treated with first-line palbociclib/letrozole with initial clinical response, and at progression was switched to capecitabine with no response. Repeat biopsy of the axillary lesion showed evolution of the tumor into a triple negative breast cancer. She was then treated with third-line paclitaxel and radiation therapy with good initial response. She eventually had further disease progression and presented with a new mediastinal lymphadenopathy causing SVC syndrome. Biopsy of this showed a small cell variant of breast neuroendocrine carcinoma. Due to the evolution of histology in this case, a retrospective review of her initial breast specimen as well as the second biopsy from the axilla was conducted which confirmed that the mediastinal lymphadenopathy was metastatic from the original breast tumor.

OUTCOMES AND LESSONS: We speculate that the initial treatment allowed a minority of treatment-resistant neuroendocrine cells to grow and become the dominant face of the tumor. Our patient had an excellent response to carboplatin/etoposide and consolidative locoregional radiotherapy but presented with an early intracranial recurrence. This is a similar pattern of metastases as seen in lung SCC and highlights a potential role for prophylactic cranial irradiation in breast SCC. Further studies are needed to better understand the biology and treatment of breast SCC which continues to present a challenge for clinicians.}, } @article {pmid35027533, year = {2022}, author = {Makower, D and Qin, J and Lin, J and Xue, X and Sparano, JA}, title = {The 21-gene recurrence score in early non-ductal breast cancer: a National Cancer Database analysis.}, journal = {NPJ breast cancer}, volume = {8}, number = {1}, pages = {4}, pmid = {35027533}, issn = {2374-4677}, support = {UL1 TR002556/TR/NCATS NIH HHS/United States ; }, abstract = {The 21-gene recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit in early estrogen receptor-positive (ER +) HER2-negative (HER2-) breast cancer (BCA). We evaluated clinicopathologic characteristics, RS and chemotherapy benefit in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and carcinomas of mixed histologies (ductal + lobular (DLC), ductal + other (DOC), lobular + other (LOC)). Women diagnosed between 1/1/2010 and 1/1/2014 with ER + HER2- BCA, measuring <5 cm, with 0-3 involved axillary nodes, surgery as first treatment, and available RS, were identified from the NCDB. Associations between categorical variables were examined using chi-square test. Cox proportional hazards model was used to examine overall survival (OS) differences among histology subtypes. IDC was associated with smaller size, high grade, and RS > 26. ILC was associated with larger size, and least likely to be high grade (p < 0.0001). Lobular histology was associated with lower incidence of RS > 26. IDC patients (pts) were more likely to receive chemotherapy than pts with other histologies (p < 0.0001). OS for IDC, ILC and DOC were similar. DLC was associated with improved OS (HR 0.82, p = 0.02). Adjuvant chemotherapy was associated with improved OS in IDC (HR = 0.76, p < 0.0001) but not in ILC (HR = 0.99, p = 0.93), DLC (HR = 1.04, p = 0.86), DOC (HR = 0.87, p = 0.71), or LOC (HR = 2.91, p = 0.10). Lobular and mixed BCA histologies have distinct clinicopathologic features compared with IDC, and are less likely to have high RS. OS is similar for IDC and ILC. Although chemotherapy benefit was seen only in IDC, benefit for ILC with RS > 26 cannot be excluded.}, } @article {pmid35022341, year = {2022}, author = {Kawaguchi, Y and Kuba, S and Morita, M and Meng, X and Hayashi, H and Kobayashi, K and Adachi, T and Hidaka, M and Itoh, S and Kanetaka, K and Eguchi, S}, title = {Bilateral Inflammatory Breast Cancer That Developed Two Years after Treatment for Triple-negative Breast Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {61}, number = {15}, pages = {2387-2391}, pmid = {35022341}, issn = {1349-7235}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols ; *Breast Neoplasms/drug therapy ; Epirubicin/adverse effects ; Female ; Humans ; *Inflammatory Breast Neoplasms/surgery ; Lymph Node Excision ; Mastectomy ; Sentinel Lymph Node Biopsy ; *Triple Negative Breast Neoplasms/surgery ; }, abstract = {A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.}, } @article {pmid35012758, year = {2022}, author = {Gault, N and Sallah, K and Régent, A and Le Jeunne, C and Lechat, P}, title = {[Analysis of off-label prescriptions of medicines in hospital in adult patients and feasibility study of their detection using CIM-10 coding].}, journal = {Therapie}, volume = {77}, number = {3}, pages = {329-338}, doi = {10.1016/j.therap.2021.10.005}, pmid = {35012758}, issn = {1958-5578}, mesh = {Adult ; Delivery of Health Care ; Feasibility Studies ; Hospitals ; Humans ; *Off-Label Use ; *Prescriptions ; }, abstract = {UNLABELLED: Analysis of off-label prescriptions of medicines in hospital in adult patients and study of feasibility of their detection by use of international disease classification, 10th version (IDC-10 codes).

CONTEXT: In order to improve the appropriate use of medicines, a method of detection of off label prescriptions, especially in hospitalised patients, should be available.

STUDY OBJECTIVES: Evaluate the performance of the detection of off-label prescriptions in hospitalised patients by use of IDC-10 codes.

METHODS: Data prescriptions (excluding those directly taken in charge by the national health care system), clinical history and biological results were extracted from Assistance publique des Hôpitaux de Paris (AP-HP) data-warehouse for 108 in-hospital adults patients' journeys. An adjudication committee established the classification reference for the appropriate or off label drug prescriptions status after analysis of medical information for each patient. IDC-10 codification that is performed after every hospitalisation was crossed with those IDC-10 codes that were to be expected corresponding to the marketing authorisation labelling (section 4.1 of specifications of product characteristics [SPC]). Results of IDC-10 coding were compared to the reference for off label use identification.

RESULTS: Out of the 1131 analysed prescriptions, 44 (3.9%) were classified as off label by the adjudication committee. Sensitivity of detection by IDC-10 coding was 87 (95% CI [0.73-0.96]) to 92% (95% CI [0.79-0.98]) and specificity 25 (95% CI [0.22-0.27]) to 41% (95% CI [0.38-0.44]) according to the number of characters of ICD-10 that could be used.

CONCLUSIONS: Incidence of in-hospital off label use of drugs (restricted to within drug related groups prescriptions) appeared relatively low (3.9%). Its semi-automatic detection by IDC-10 coding appears feasible with a good sensitivity but a low specificity. Such method could be further assessed as a first step detection focusing on one pharmacological class or on one pathologic condition.}, } @article {pmid35011787, year = {2021}, author = {Rachamim, L and Mualem-Taylor, H and Rachamim, O and Rotstein, M and Zimmerman-Brenner, S}, title = {Acute and Long-Term Effects of an Internet-Based, Self-Help Comprehensive Behavioral Intervention for Children and Teens with Tic Disorders with Comorbid Attention Deficit Hyperactivity Disorder, or Obsessive Compulsive Disorder: A Reanalysis of Data from a Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {11}, number = {1}, pages = {}, pmid = {35011787}, issn = {2077-0383}, abstract = {Attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and tic disorders (TD) commonly co-occur. In addition, specific inattention difficulties and poor impulse control are related to TD in the absence of comorbid ADHD. In this study we reanalyzed data from a recently completed study comparing internet-delivered, self-help comprehensive behavioral intervention for tics (ICBIT) with a waiting-list control group. The current study describes the effects of an (ICBIT) in children and adolescents with TD with and without comorbid diagnoses of ADHD or OCD at post intervention and over three- and six-month follow-up periods. Thirty-eight 7 to 18-year-olds completed the ICBIT. Of these, 16 were diagnosed with comorbid ADHD and 11 were diagnosed with OCD. A significant improvement in tic measures was found in all groups. Both the TD + ADHD and the TD - ADHD groups were similar in the magnitude of tic reduction from baseline to post-treatment, and at the three and six-month follow-up assessments. However, the TD + OCD group benefitted less from intervention than the TD-OCD group. There were meaningful reductions in parental reports of inattention, as well as hyperactive and impulsive symptoms at post intervention and over the 6-month follow-up period. Thus, ICBIT can be effectively delivered in the presence of comorbid ADHD or OCD symptomatology and may reduce symptoms of inattention and impulsivity. Larger studies of ICBIT in children and teens with TD and comorbid ADHD and OCD are needed to optimize responses to ICBIT.}, } @article {pmid35011590, year = {2021}, author = {Greulich, F and Bielefeld, KA and Scheundel, R and Mechtidou, A and Strickland, B and Uhlenhaut, NH}, title = {Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.}, journal = {Cells}, volume = {11}, number = {1}, pages = {}, pmid = {35011590}, issn = {2073-4409}, support = {GR 5179/1-1//Deutsche Forschungsgemeinschaft/ ; UH 275/1-1//Deutsche Forschungsgemeinschaft/ ; ERC-2014-StG 638573/ERC_/European Research Council/International ; TRR205, The Adrenal//Deutsche Forschungsgemeinschaft/ ; CRC1064 Chromatin Dynamics//Deutsche Forschungsgemeinschaf/ ; }, mesh = {Acetylation/drug effects ; Animals ; Binding Sites ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Glucocorticoids/*pharmacology ; Histones/metabolism ; Lysine/metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism ; Organ Specificity/drug effects ; RNA/*genetics/metabolism ; Receptors, Glucocorticoid/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; }, abstract = {Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.}, } @article {pmid35008253, year = {2021}, author = {Geppert, J and Walth, AA and Terrón Expósito, R and Kaltenecker, D and Morigny, P and Machado, J and Becker, M and Simoes, E and Lima, JDCC and Daniel, C and Berriel Diaz, M and Herzig, S and Seelaender, M and Rohm, M}, title = {Aging Aggravates Cachexia in Tumor-Bearing Mice.}, journal = {Cancers}, volume = {14}, number = {1}, pages = {}, pmid = {35008253}, issn = {2072-6694}, support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {BACKGROUND: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models.

METHODS: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer.

RESULTS: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients.

CONCLUSIONS: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.}, } @article {pmid35008028, year = {2022}, author = {Mikulincer, M and Shaver, PR}, title = {An attachment perspective on loss and grief.}, journal = {Current opinion in psychology}, volume = {45}, number = {}, pages = {101283}, doi = {10.1016/j.copsyc.2021.11.003}, pmid = {35008028}, issn = {2352-2518}, mesh = {Adaptation, Psychological ; Adult ; *Bereavement ; Divorce ; Grief ; Humans ; }, abstract = {Attachment theory provides a useful framework for understanding emotional reactions to separation and loss and the process of adapting to these painful events. In this article, we review adult attachment studies that have examined emotional reactions and adjustment to separation and loss in romantic and marital relationships. We begin with a brief account of attachment theory. Next, we review studies examining the emotional consequences of losing a relationship partner and the coping responses that can help a person adjust to this loss. Throughout the article, we also summarize research documenting attachment-related individual differences in responses to separation and loss. (99 words).}, } @article {pmid35003765, year = {2021}, author = {Pereira, C and Martis, M and D'Souza, R and Tauro, LF}, title = {Correlation of Clinicopathological Features of Breast Cancer with Molecular Subtypes Taking Ki-67 into Consideration: Single Institution Experience Over 5 Years.}, journal = {Current health sciences journal}, volume = {47}, number = {3}, pages = {348-352}, pmid = {35003765}, issn = {2067-0656}, abstract = {BACKGROUND: Molecular classification of breast cancer is commonly done to determine response to therapy and cancer prognosis. Aim of the study was to compare prevalence of molecular subtypes of breast cancer in our institute using immunohistochemistry, including Ki-67, and correlate it with clinical and pathological prognostic factors.

RESULTS: 300 cases of invasive breast cancer were included in the study. Average age at time of diagnosis was 44 years and average size of tumor was 3.4cms. Invasive ductal carcinoma was the most common histological type (75.3%). The most common molecular subtype was triple negative (34.3%) followed by Luminal B (33.4%), luminal A (17%) and Her-2 positive (15.3%). Large size and poorly differentiated tumors were predominantly triple negative tumors while lymph node metastasis was most commonly seen in Her-2 positive tumors.

CONCLUSION: Molecular subtype of breast carcinoma should routinely be done for all cases of carcinoma breast as it allows to identify aggressive tumors and target therapy accordingly.}, } @article {pmid34999881, year = {2022}, author = {Aftab, F and Ahmed, S and Ali, SM and Ame, SM and Bahl, R and Baqui, AH and Chowdhury, NH and Deb, S and Dhingra, U and Dutta, A and Hasan, T and Hotwani, A and Ilyas, M and Javaid, M and Jehan, F and Juma, MH and Khalid, F and Khanam, R and Manu, AA and Mehmood, U and Minckas, N and Mitra, DK and Nisar, I and Polašek, O and Rahman, S and Rudan, I and Sajid, M and Sazawal, S and Yoshida, S and , }, title = {Cohort Profile: The Alliance for Maternal and Newborn Health Improvement (AMANHI) biobanking study.}, journal = {International journal of epidemiology}, volume = {50}, number = {6}, pages = {1780-1781i}, pmid = {34999881}, issn = {1464-3685}, support = {001/WHO_/World Health Organization/International ; GRANT NUMBER I64438/WHO_/World Health Organization/International ; /GATES/Bill & Melinda Gates Foundation/United States ; }, mesh = {*Biological Specimen Banks ; Cohort Studies ; Family ; Humans ; *Infant Health ; Infant, Newborn ; }, } @article {pmid34999280, year = {2022}, author = {Kotschi, S and Jung, A and Willemsen, N and Ofoghi, A and Proneth, B and Conrad, M and Bartelt, A}, title = {NFE2L1-mediated proteasome function protects from ferroptosis.}, journal = {Molecular metabolism}, volume = {57}, number = {}, pages = {101436}, pmid = {34999280}, issn = {2212-8778}, mesh = {Animals ; *Ferroptosis ; Homeostasis ; Humans ; Mice ; Mitochondria/metabolism ; *NF-E2-Related Factor 1/genetics/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Proteasome Endopeptidase Complex/metabolism ; }, abstract = {OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.

METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.

CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.}, } @article {pmid34993063, year = {2022}, author = {Jeong, S and Kim, TH}, title = {Diffusion-weighted imaging of breast invasive lobular carcinoma: comparison with invasive carcinoma of no special type using a histogram analysis.}, journal = {Quantitative imaging in medicine and surgery}, volume = {12}, number = {1}, pages = {95-105}, pmid = {34993063}, issn = {2223-4292}, abstract = {BACKGROUND: To investigate the imaging findings and visibility of breast invasive lobular carcinoma (ILC) on diffusion-weighted imaging (DWI) and compare quantitative apparent diffusion coefficient (ADC) metrics of ILC and invasive carcinoma of no special type (NST) using a histogram analysis.

METHODS: We performed an observational retrospective study of 629 consecutive women with pathologically proven ILC and invasive ductal carcinoma of NST, who underwent 3-T MRI including DWI, between January 2017 and August 2020.

RESULTS: After propensity score matching, 71 women were allocated to each group. On DWI, 9 (12.7%) lesions of ILC and 4 (5.6%) invasive carcinomas of the NST were not visualized. For the tumor visibility on DWI, tumor size, tumor ADC value, and background diffusion grade were significantly associated with the visibility score in both groups (all P<0.05), whereas the mean background ADC value was not significant (P>0.05). The mean ADC (1.226×10[-3] vs. 1.052×10[-3] mm[2]/s, P<0.001), median ADC (1.222×10[-3] vs. 1.051×10[-3] mm[2]/s, P=0.002), maximum ADC (1.758×10[-3] vs. 1.504×10[-3] mm[2]/s, P<0.001), minimum ADC (0.717×10[-3] vs. 0.649×10[-3] mm[2]/s, P=0.003), 90th percentile ADC (1.506×10[-3] vs. 1.292×10[-3] mm[2]/s, P<0.001) and 10th percentile ADC (0.956×10[-3] vs. 0.818×10[-3] mm[2]/s, P=0.008) were higher in ILC than in invasive carcinoma of NST. Additionally, the ADC difference value of the ILC was higher than that of invasive carcinoma of NST (1.04×10[-3] vs. 0.855×10[-3] mm[2]/s, P=0.027).

CONCLUSIONS: On DWI, the visibility of ILC was lower compared to invasive carcinoma of NST. ILC showed higher quantitative ADC values and higher ADC difference values.}, } @article {pmid34987224, year = {2022}, author = {Rasmussen, M and Reddy, M and Nolan, R and Camunas-Soler, J and Khodursky, A and Scheller, NM and Cantonwine, DE and Engelbrechtsen, L and Mi, JD and Dutta, A and Brundage, T and Siddiqui, F and Thao, M and Gee, EPS and La, J and Baruch-Gravett, C and Santillan, MK and Deb, S and Ame, SM and Ali, SM and Adkins, M and DePristo, MA and Lee, M and Namsaraev, E and Gybel-Brask, DJ and Skibsted, L and Litch, JA and Santillan, DA and Sazawal, S and Tribe, RM and Roberts, JM and Jain, M and Høgdall, E and Holzman, C and Quake, SR and Elovitz, MA and McElrath, TF}, title = {RNA profiles reveal signatures of future health and disease in pregnancy.}, journal = {Nature}, volume = {601}, number = {7893}, pages = {422-427}, pmid = {34987224}, issn = {1476-4687}, support = {P50 HD103556/HD/NICHD NIH HHS/United States ; }, mesh = {*Cell-Free Nucleic Acids/blood ; Female ; Humans ; *Pre-Eclampsia/diagnosis/genetics ; Predictive Value of Tests ; Pregnancy ; *RNA/blood ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden[1]. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method[2]. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.}, } @article {pmid34985683, year = {2022}, author = {McLean-Holden, AC and Rooper, LM and Lubin, DJ and Magliocca, KR and Manucha, V and Sadow, PM and Tobias, J and Vargo, RJ and Thompson, LDR and Heidarian, A and Weinreb, I and Wenig, B and Gagan, J and Hernandez-Prera, JC and Bishop, JA}, title = {Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology.}, journal = {Head and neck pathology}, volume = {16}, number = {3}, pages = {657-669}, pmid = {34985683}, issn = {1936-0568}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; }, mesh = {*Adenocarcinoma ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; *Carcinoma, Ductal ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Gene Fusion ; Humans ; Male ; Middle Aged ; Receptor Protein-Tyrosine Kinases ; *Salivary Gland Neoplasms ; Transcription Factors ; }, abstract = {Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.}, } @article {pmid34984130, year = {2021}, author = {Betlloch-Mas, I and Soriano-García, T and Boira, I and Palazón, JC and Juan-Carpena, G and Sancho-Chust, JN and Chiner, E}, title = {Cutaneous Metastases of Solid Tumors: Demographic, Clinical, and Survival Characteristics.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19970}, pmid = {34984130}, issn = {2168-8184}, abstract = {BACKGROUND: Cutaneous metastasis (CM), while uncommon, is usually an indicator of poor prognosis. With cancer patients living longer, the incidence of CM has increased, which justifies its analysis.

OBJECTIVES: The objective of this study was to carry out a descriptive study of CM diagnosed for 18 years in a dermatology department of a tertiary care hospital and to assess the epidemiological, clinical, and histological variables that condition them, as well as data on their survival and prognosis.

METHODS: We performed a descriptive study of cases of CM diagnosed over 18 years in the dermatology department of a tertiary referral hospital analyzing the following variables: patient age and sex, site of primary neoplasm, pathochronology, survival time, histological findings, immunohistochemical markers, the anatomical area affected, the clinical appearance of the metastasis, therapeutic plan, and existence of metastases in other regions. We checked normal distribution using the Kolmogorov-Smirnov test and then compared the quantitative variables using the Student's t-test (unpaired samples), Mann-Whitney test (non-normal distribution), analysis of variance (ANOVA; for more than two groups), and categorical variables using the chi-square or Fisher's exact test.

RESULTS: We included 37 cases (20 men and 17 women), of whom 32 had died. The mean age was 62 ± 15 years. CM detection was defined early in 8% of cases, synchronous in 32%, and metachronous in 60%. The most frequent primary tumor sites were lungs (24%), breasts (21%), and bladders (11%). Most metastases were solitary. The most frequent locations for CM were the scalp, trunk, armpits, and groin. Most lesions had a nodular presentation (81%). Squamous cell carcinoma and adenocarcinoma showed the same frequency in lung cancer CM. Breast cancer leading to CM was the most common invasive ductal carcinoma. The most aggressive cases, with the worst survival, originated in lung neoplasms. Therapeutic management for most patients involved surgery in combination with other procedures. The only difference detected between the lung and breast cancer CM was the predominance of lung tumors in men (89%) and breast tumors in women compared with metastases from other sites; breast cancer CM manifested more frequently as plaques and less frequently as nodules (p < 0.05) and was less frequently associated with multisystemic metastasis. In lung cancer CM, time from tumor diagnosis to CM occurrence was shorter (p < 0.01) and multisystemic metastasis was more frequent than in CM of other tumors.

CONCLUSIONS: CM tends to affect patients aged above 60 years and arises predominantly from lung cancer in men and breast cancer in women. The most typical locations are the chest and scalp, and the appearance is usually nodular. Survival after CM detection is low, particularly in lung cancer CM.}, } @article {pmid34977692, year = {2022}, author = {Remmers, S and Nieboer, D and Rijstenberg, LL and Hansum, T and van Leenders, GJLH and Roobol, MJ}, title = {Updating the Rotterdam Prostate Cancer Risk Calculator with Invasive Cribriform and/or Intraductal Carcinoma for Men with a Prior Negative Biopsy.}, journal = {European urology open science}, volume = {36}, number = {}, pages = {19-22}, pmid = {34977692}, issn = {2666-1683}, abstract = {UNLABELLED: The Rotterdam Prostate Cancer Risk Calculator (RPCRC) is a well-validated tool for upfront risk stratification to reduce the number of prostate biopsies and magnetic resonance imaging scans among both biopsy-naïve and previously biopsied men. The presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) identifies men with aggressive grade group (GG) 2 tumors. This finding was recently incorporated in the RPCRC for biopsy-naïve men to predict the probability of no PCa, indolent PCa (GG 1 disease and GG 2 disease without CR/IDC), and clinically significant PCa (csPCa: GG 2 disease with CR/IDC and higher). The aim of the current study was to update the RPCRC for men with a previous negative biopsy with the presence of CR/IDC. A total of 2215 men were eligible for analyses, of whom 1776 (80%) were not diagnosed with PCa, 358 (16%) were diagnosed with indolent PCa, and 81 (4%) were diagnosed with csPCa according to the original 2014 Gleason grading. The optimism-corrected area under the curve was 0.69 for any PCa and 0.77 for csPCa. With a threshold of 10% for indolent PCa or 1% for csPCa, 20% of all prostate biopsies could be avoided and 2% of all csPCa cases would be missed. Our results support upfront risk stratification with the updated RPCRC.

PATIENT SUMMARY: Risk stratification for men without a prior diagnosis of prostate cancer can reduce the number of prostate biopsies and magnetic resonance imaging scans carried out in this patient population. Our study shows that it is possible to update the Rotterdam Prostate Cancer Risk Calculator for men with a previous negative biopsy with the presence of invasive cribriform and/or intraductal carcinoma.}, } @article {pmid34976715, year = {2021}, author = {Constantin, A and Alexandru, C and Korte, J and Wilson, C and Fails, JA and Sim, G and Read, JC and Eriksson, E}, title = {Distributing participation in design: Addressing challenges of a global pandemic.}, journal = {International journal of child-computer interaction}, volume = {28}, number = {}, pages = {100255}, pmid = {34976715}, issn = {2212-8689}, abstract = {Participatory Design (PD) - whose inclusive benefits are broadly recognised in design - can be very challenging, especially when involving children. The recent COVID-19 pandemic has given rise to further barriers to PD with such groups. One key barrier is the advent of social distancing and government-imposed social restrictions due to the additional risks posed for e.g. children and families vulnerable to COVID-19. This disrupts traditional in-person PD (which involves close socio-emotional and often physical collaboration between participants and researchers). However, alongside such barriers, we have identified opportunities for new and augmented approaches to PD across distributed geographies, backgrounds, ages and abilities. We examine Distributed Participatory Design (DPD) as a solution for overcoming these new barriers, during and after COVID-19. We offer new ways to think about DPD, and unpick some of its ambiguities. We do this through an examination of the results from an online Interaction Design and Children (IDC) 2020 workshop. The workshop included 24 researchers with experience in PD, in a range of forms, in the context of children. Initially designed to take place in-person and to include a design session with children in a school in London, the workshop was adjusted to an online format in response to the COVID-19 pandemic. Despite the adverse circumstances, we discovered that the unexpected change of the workshop style from in-person to online was an opportunity and an impetus for us to address the new PD challenges of the global pandemic. In this article we contribute seven themes which were revealed during our IDC workshop, providing guidance on important areas for consideration when planning and conducting PD in the context of a global pandemic. With a focus on the term 'distributed', we offer insights on how DPD can be applied and explored in these circumstances with child participants. We conclude with a number of lessons learned, highlighting the opportunities and challenges DPD offers to enable continued co-design during a global pandemic. In particular, DPD provides greater access for some populations to be involved in PD, but technical and social challenges must be addressed.}, } @article {pmid34975349, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E}, title = {Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.}, journal = {TheScientificWorldJournal}, volume = {2021}, number = {}, pages = {6672274}, pmid = {34975349}, issn = {1537-744X}, mesh = {*Body Mass Index ; *Exercise Therapy ; Female ; Humans ; Lower Extremity/*physiopathology ; Male ; Middle Aged ; Obesity/*complications ; Osteoarthritis, Knee/complications/physiopathology/*rehabilitation ; Overweight/*complications ; Pain/*complications ; Range of Motion, Articular ; Single-Blind Method ; }, abstract = {BACKGROUND: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.

RESULTS: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p ≤ 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.

CONCLUSION: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.}, } @article {pmid34972731, year = {2022}, author = {Salih, MM and Higgo, AA and Eed, EM}, title = {Prognostic Significance of p16 Protein Expression in Breast Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {36}, number = {1}, pages = {336-340}, pmid = {34972731}, issn = {1791-7549}, mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Female ; Humans ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND/AIM: Breast cancer is the most common cancer in Sudan. The p16 protein plays a vital role in the regulation of the cell cycle.

PATIENTS AND METHODS: This study analysed the protein expression of p16 in 202 paraffin blocks from Sudanese women with breast cancer using immunohistochemistry.

RESULTS: This study included 168 (83.2%), 16 (7.9%), and 18 (8.9%) patients with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. There were 95 cases (47.0%) with grade III, 70 cases (34.6%) with grade II, and 23 cases (11.4%) with grade I breast cancer. The hormone receptor status was available for 119 of the cases, and 31 (15.3%), 25 (12.4%), and 63 (31.2%) cases were positive for oestrogen, progesterone, and HER2 receptors, respectively.

CONCLUSION: p16 protein expression was associated with high histologic grade, lymph node metastasis, and poor prognosis. p16 protein expression may potentially be used as a prognostic marker.}, } @article {pmid34969739, year = {2022}, author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Shibutani, M and Tanaka, H and Hirakawa, K and Ohira, M}, title = {The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Breast Carcinoma: A Retrospective Study.}, journal = {Anticancer research}, volume = {42}, number = {1}, pages = {311-320}, doi = {10.21873/anticanres.15487}, pmid = {34969739}, issn = {1791-7530}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/chemically induced/*diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis/*diagnosis/diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy/methods ; Smoking/*adverse effects ; }, abstract = {BACKGROUND/AIM: If ductal carcinoma in situ (DCIS) is diagnosed by needle biopsy, invasion is often found by removing the entire tumor and performing pathological examination. Smoking is a risk factor for carcinogenesis in breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients diagnosed with DCIS by preoperative biopsy.

PATIENTS AND METHODS: We examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.

RESULTS: Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy. Number of pack-years was not an independent factor (p=0.349, OR=0.329), but current-smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).

CONCLUSION: Tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.}, } @article {pmid34967546, year = {2021}, author = {Abbasi, A and Rahimi, S and Mahmoudzadeh, L and Mojdeganlou, H}, title = {High grade breast ductal carcinomas have high density of tumor-associated macrophages.}, journal = {Experimental oncology}, volume = {43}, number = {4}, pages = {328-330}, doi = {10.32471/exp-oncology.2312-8852.vol-43-no-4.16898}, pmid = {34967546}, issn = {2312-8852}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mastectomy ; Prognosis ; Tumor-Associated Macrophages ; }, abstract = {BACKGROUND: The role of tumor-associated macrophages (TAMs) is double-natured and still controversial. Depending on different settings, macrophages may suppress or promote tumor growth. TAM density may be one of the predictive factors of treatment outcome in cancer patients.

AIM: To evaluate the density of tumor-associated macrophages in breast cancer and its relationship with various histopathologic findings.

MATERIALS AND METHODS: 55 patients with invasive ductal carcinoma of breast who underwent mastectomy were enrolled. Sections of tumor samples were stained and the density of CD68[+] cells was evaluated.

RESULTS: There was an association between estrogen receptor (ER) expression and CD68 density (p = 0.010) as the higher densities of CD68 were seen in ER negative tumors. Moreover, there was a significant relationship between histological grade and CD68 density (p = 0.006).

CONCLUSION: The higher TAM density is associated with higher tumor grade and negative ER expression in breast cancer tissues. These findings revealed that inflammation could have an important role in malignancies.}, } @article {pmid34964158, year = {2022}, author = {Mikoshi, A and Miyai, K and Hamabe, F and Edo, H and Ito, K and Matsukuma, S and Tsuda, H and Shinmoto, H}, title = {MRI-detectability and histological factors of prostate cancer including intraductal carcinoma and cribriform pattern.}, journal = {The Prostate}, volume = {82}, number = {4}, pages = {452-463}, doi = {10.1002/pros.24291}, pmid = {34964158}, issn = {1097-0045}, mesh = {Aged ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Humans ; Male ; Middle Aged ; *Multiparametric Magnetic Resonance Imaging ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Preoperative Period ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Histopathological characteristics affecting the detectability of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI) remain unclear. This study aimed to compare the histopathology between MRI-detectable and MRI-undetectable cancers, emphasizing intraductal carcinoma of the prostate (IDC-P) and predominant Gleason pattern 4 subtype.

METHODS: This single-center retrospective study enrolled 153 consecutive patients with 191 lesions who underwent preoperative multiparametric MRI and subsequent radical prostatectomy. MRI/histopathological findings and area fractions of histological components (cancer cells, stroma, and luminal spaces) of MRI-detectable and MRI-undetectable cancers were compared. Data were analyzed using Fisher's exact, independent t, or Mann-Whitney U tests.

RESULTS: Overall, 148 (77%) and 43 (23%) cancers were MRI-detectable and MRI-undetectable, respectively. MRI-detectable cancers were significantly larger than MRI-undetectable cancers (p = 0.03). The percentage of lesions in Grade Group 3 or higher was significantly higher among MRI-detectable cancers than among MRI-undetectable cancers (p = 0.02). MRI detectability of csPCa was associated with increases in relative area fractions of cancer cells (p < 0.001) and decreases in those of stroma (p < 0.001) and luminal spaces (p < 0.001) in prostate cancer (PCa) than the percentage of Gleason pattern 4 (p = 0.09). The percentage of lesions containing IDC-P was similar for MRI-detectable and MRI-undetectable cancers (40% vs. 33%; p = 0.48). The distribution of cribriform gland subtypes was not significantly different between MRI-detectable and MRI-undetectable Gleason pattern 4 subtype cancers (p > 0.99). Contrarily, the ratio of fused gland subtype was significantly higher in MRI-detectable than in MRI-undetectable cancers (p = 0.03). Furthermore, the ratio of poorly-formed gland subtype was significantly higher in MRI-undetectable than in MRI-detectable cancers (p = 0.01).

CONCLUSIONS: MRI detectability of csPCa is strongly associated with the relative area fractions of cancer cells, stroma, and luminal spaces in PCa rather than conventional histopathological parameters. Neither the presence nor the percentage of IDC-P affected MRI detectability.}, } @article {pmid34963837, year = {2021}, author = {Azhar, M and Hamdani, SAM and Iftikhar, J and Ahmad, W and Mushtaq, S and Kalsoom Awan, UE}, title = {An Unusual Occurrence of Uterine Metastases in a Case of Invasive Ductal Breast Carcinoma.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19820}, pmid = {34963837}, issn = {2168-8184}, abstract = {Breast cancer is the most frequent cancer in women and has a high proclivity for metastasizing, yet it seldom affects gynaecological organs. We present a case of invasive ductal carcinoma of the breast that metastasized to the uterus following initial curative treatment. Our patient was taking tamoxifen, which can induce endometrial hyperplasia and make diagnosis more complicated.}, } @article {pmid34950479, year = {2021}, author = {Adachi, Y and Katsuki, T and Sasaguri, T and Hirata, K and Nagata, N}, title = {Invasive cribriform carcinoma of the breast detected incidentally on computed tomography: A case report.}, journal = {Clinical case reports}, volume = {9}, number = {12}, pages = {e05214}, pmid = {34950479}, issn = {2050-0904}, abstract = {Invasive cribriform carcinoma is a rare type of invasive breast carcinoma, and a few cases have been reported. Its features are a cribriform pattern resembling the histological structures of cribriform ductal carcinoma in situ and an excellent prognosis. However, the extent of progress for intraductal extension must be carefully evaluated.}, } @article {pmid34950005, year = {2021}, author = {Caterino, U and Cesaro, C and Zamparelli, E and Cesaro, F and Palma, A and Lucci, R and Imitazione, P and Casazza, D and Amore, D}, title = {Different Therapeutic Strategies in 2 Young Patients with Advanced ALK-Rearranged Lung Adenocarcinoma: "The Light at the End of the Tunnel".}, journal = {Case reports in oncology}, volume = {14}, number = {3}, pages = {1616-1620}, pmid = {34950005}, issn = {1662-6575}, abstract = {Malignant pleural effusion represents a prognostic negative factor on survival conferring stage IV disease. The median of survival is 5 months and a 5-year survival of about 3%. We describe the therapeutic success obtained from different strategies in anaplastic lymphoma kinase (ALK) inhibitors in 2 young women showing malignant pleural effusion secondary to advanced ALK-rearranged lung adenocarcinoma. This report shows that for patients with EGFR mutations in advanced lung adenocarcinoma-associated malignant pleural effusion, complete response to EGFR TKI inhibitor can be observed mostly if pleural effusion and primary lung adenocarcinoma show the same EGFR mutation status.}, } @article {pmid34949236, year = {2021}, author = {Mthembu, JG and Bhuiyan, M}, title = {Profile of molecular subtyping of breast cancer and clinicopathological features in Mankweng Hospital breast oncology clinic, Limpopo Province, South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {111}, number = {11b}, pages = {1132-1135}, doi = {10.7196/SAMJ.2021.v111i11b.16104}, pmid = {34949236}, issn = {2078-5135}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; South Africa/epidemiology ; }, abstract = {BACKGROUND: Breast cancer is recognised as a heterogeneous disorder, comprising a number of subcategories of several cellular compositions, molecular alterations as well as clinical behaviour. Across the world, research has been able to show that the most common molecular subtype is luminal A, followed by triple negative and human epidermal receptor 2 (HER2)-positive (non-luminal) subtype. However, another study found that the most common molecular subtype was HER2/neu amplification, suggesting that subtypes case frequencies differ in different people.

OBJECTIVES: To determine the case frequency of molecular subtypes of breast cancers and the associated clinicopathological features in women from Limpopo Province, South Africa.

METHOD: We performed a retrospective, cross-sectional descriptive study from July 2021 - June 2021 at Mankweng Hospital breast oncology clinic. The inclusion criterion was all women with histologically confirmed breast cancer.

RESULT: We identified 222 women who met the inclusion criteria, and the age range (median) was 25 - 91 (54.8) years. The majority of the women came from the Vhembe district (28%; n=62), followed by Capricorn district (26%; n=59), Mopani district (17%; n=38), Sekhukhune district (16%; n=35), and Waterberg district (13%; n=28). Histology revealed that the most common type was invasive ductal carcinoma (no special type; 91.44%; n=203), followed by invasive mucinous carcinoma (4%; n=9). The most predominant molecular subtype was luminal B (48.19%; n=107), followed by luminal A (22.97%; n=51), triple negative (17.12%; n=38) and 11.75% (n=26) overexpressed HER2. More than one-third of the cancers were HER2-positive (40.54%; n=90), and 59.46% (n=132) were HER2-negative. The majority of patients presented with late-stage cancer (62.16%; n=138), and the rest presented with early-stage (I and II) disease (37.84%; n=84).

CONCLUSION: The majority of our patients had luminal subtypes and hormonal receptor-positive breast cancers, which should be associated with very good clinical outcomes. However, the majority of patients presented late with advanced-stage disease and high Ki-67 expression. Therefore, research is required to help us understand why in our context patients present late with advanced-stage disease.}, } @article {pmid34949235, year = {2021}, author = {Mavhungu, R and Bhuiyan, M and Ooko, F}, title = {Profile of patients seen at Pietersburg and Mankweng breast cancer clinics in Limpopo.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {111}, number = {11b}, pages = {1129-1131}, doi = {10.7196/SAMJ.2021.v111i11b.16108}, pmid = {34949235}, issn = {2078-5135}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology ; Breast Neoplasms, Male/epidemiology/pathology ; Female ; Humans ; Incidence ; Male ; Mammography ; Middle Aged ; Neoplasm Staging ; Prevalence ; Retrospective Studies ; South Africa/epidemiology ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer diagnosed among women worldwide. It is the most prevalent cancer and leading cause of death among South African (SA) women. The increasing incidence of breast cancer is a major health concern. Until now, the distribution of breast cancer demography, stage at first presentation, and histological characterisation have not been studied in Limpopo Province, SA.

OBJECTIVES: To record the demographic profile of breast cancer patients, to report the stage at the time of presentation and to characterise the pattern of malignant disease in Limpopo, SA.

METHODS: We conducted a retrospective descriptive review of the records of patients managed at Pietersburg Hospital oncology and Mankweng Hospital breast cancer clinics during the period 1 March 2015 - 28 February 2017. Stata was used to analyse data.

RESULTS: A total of 248 patients with a mean age of 55 years were included for analysis, 7 males (3%) and 241 females (97%). Capricorn and Vhembe districts constituted 32% and 27% respectively. The majority (69%) of patients were diagnosed with disease stage III or IV. The most common histological type was invasive ductal cell carcinoma (IDC) (87%).

CONCLUSIONS: More than one-third of patients were younger than 50 years. The majority (69%) had an advanced breast cancer (stage III or IV). We recommend provision of mammography services in regional hospitals.}, } @article {pmid34945830, year = {2021}, author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY}, title = {Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.}, journal = {Journal of personalized medicine}, volume = {11}, number = {12}, pages = {}, pmid = {34945830}, issn = {2075-4426}, abstract = {BACKGROUND: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

PATIENTS AND METHODS: we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).

RESULTS: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group.

CONCLUSION: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.}, } @article {pmid34944863, year = {2021}, author = {Diop, MK and Albadine, R and Kougioumoutzakis, A and Delvoye, N and Hovington, H and Bergeron, A and Fradet, Y and Saad, F and Trudel, D}, title = {Identification of Morphologic Criteria Associated with Biochemical Recurrence in Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {13}, number = {24}, pages = {}, pmid = {34944863}, issn = {2072-6694}, support = {CRP-154487/CAPMC/CIHR/Canada ; CRP-154487//Cancer Research Society/ ; N/A//Institut du cancer de Montréal/ ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer strongly associated with an increased risk of biochemical recurrence (BCR). However, approximately 40% of men with IDC-P remain BCR-free five years after radical prostatectomy. In this retrospective multicenter study, we aimed to identify histologic criteria associated with BCR for IDC-P lesions. A total of 108 first-line radical prostatectomy specimens were reviewed. In our test cohort (n = 39), presence of larger duct size (>573 µm in diameter), cells with irregular nuclear contours (CINC) (≥5 CINC in two distinct high-power fields), high mitotic score (>1.81 mitoses/mm[2]), blood vessels, and comedonecrosis were associated with early BCR (<18 months) (p < 0.05). In our validation cohort (n = 69), the presence of CINC or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09-4.96, p = 0.029). When combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21-6.19, p = 0.015). Our results suggest that IDC-P can be classified as low versus high-risk of BCR. The defined morphologic criteria can be easily assessed and should be integrated for clinical application following validation in larger cohorts.}, } @article {pmid34934587, year = {2021}, author = {Tan, CMP and Kaliya-Perumal, AK and Ho, GWK and Oh, JY}, title = {Postoperative Urinary Retention Following Thoracolumbosacral Spinal Fusion: Prevalence, Risk Factors, and Outcomes.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19724}, pmid = {34934587}, issn = {2168-8184}, abstract = {Objective Postoperative urinary retention (POUR) is an often-underestimated common complication following spine surgery, and it is essential to avoid its untoward long-term consequences. Besides, a dilemma exists regarding the appropriate timing for the postoperative removal of indwelling catheter (IDC). Hence, we aim to describe the prevalence, risk factors, and outcomes of POUR and also come up with recommendations for the removal of IDC. Methods Electronic records of patients who underwent elective thoracolumbosacral spinal fusion surgery from January 2017 to December 2019 were retrospectively reviewed. Excluded were those who underwent fusion for indications such as trauma, cauda equina syndrome, infection, and malignancy. Both surgery-related and patient-related risk factors were tabulated, and their association with the likely development of POUR was assessed by univariate and multivariate analysis. Results One hundred sixty-eight patients (median age=64.1 years; 58.9% female) were included, with the incidence of POUR being 7.8%. Our findings suggest surgery-related factors, both intra- and postoperative, including operating time (p=0.008), anesthetic time (p=0.005), number of fusion levels (p<0.001), mobilization status prior to trial off catheter (TOC; p=0.021), and TOC timing (p=0.029) may have an association with POUR. In addition, patient-related factors, including the use of beta-blockers (p=0.020) and pre-operative mobility status (p<0.001), may also be associated with the likely development of POUR. Conclusion POUR seems to be a frequent complication following thoracolumbosacral spinal fusion surgery, which was found to have an association with some surgery-related and patient-related factors. While most of these factors are non-modifiable, certain modifiable risk factors provide the surgeon an opportunity to prevent POUR. Considering these factors, we recommend appropriate and timely mobilization of the patient prior to removal of IDC, which is to be performed preferably in the daytime.}, } @article {pmid34934489, year = {2021}, author = {Tarrab, R and Sabouni, R and Jarad, L and Mansour, N and Saifo, MS}, title = {Metachronous breast cancer in a male with previous history of liposarcoma: A case report from Syria.}, journal = {Annals of medicine and surgery (2012)}, volume = {72}, number = {}, pages = {103151}, pmid = {34934489}, issn = {2049-0801}, abstract = {INTRODUCTION: Multiple primary cancers (MPC) are defined as the occurrence of two or more non-related cancers. The acquiring of male breast cancer (MBC) as secondary cancer in a sequence of MPC is extremely rare. Only one case of breast cancer following liposarcoma (LP) was previously reported in a female patient. We report the first case of MBC following LP.

CASE PRESENTATION: A non-smoker male patient with a history of a well-differentiated liposarcoma was treated surgically and with radiotherapy 14 years ago with no signs of recurrence. The patient presented with a left breast mass; The excisional biopsy showed poorly differentiated grade III invasive ductal carcinoma. The patient underwent a mastectomy with axillary node resection and the final diagnosis was invasive ductal carcinoma stage IIA [T:2, N:0, M:0]. The tumor markers reported; Positive Estrogen Receptor (ER+), negative Progesterone Receptor (PR-), and negative Human Epidermal Receptor (HER-). He received eight sessions of chemotherapy with Docetaxel and 16 fractions of radiotherapy. The follow-up showed no signs of recurrence.

DISCUSSION: Despite the rarity of diagnosis MBC as a second primary. Studies have found a relation between different types of breast cancer in male patients, and further, a relation was also found between MBC and lymphoma. While no studies that link MBC and LP were previously reported.

CONCLUSION: We found that acquiring a treated LP would not affect the MBC prognosis or its response to treatment, yet further studies are needed to confirm this outcome.}, } @article {pmid34934058, year = {2021}, author = {Abel, MK and Shui, AM and Melisko, M and Chien, AJ and Yoshida, EJ and Lancaster, EM and Van 't Veer, L and Esserman, LJ and Mukhtar, RA}, title = {The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study.}, journal = {NPJ breast cancer}, volume = {7}, number = {1}, pages = {156}, pmid = {34934058}, issn = {2374-4677}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; }, abstract = {When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010-2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.}, } @article {pmid34931549, year = {2021}, author = {Gebretsadik, A and Bogale, N and Negera, DG}, title = {Epidemiological Trends of Breast Cancer in Southern Ethiopia: A Seven-Year Retrospective Review.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {28}, number = {}, pages = {10732748211055262}, pmid = {34931549}, issn = {1526-2359}, mesh = {Adult ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/epidemiology ; Ethiopia/epidemiology ; Female ; Hospitals, Special ; Hospitals, University ; Humans ; Incidence ; Middle Aged ; *Population Surveillance ; Prevalence ; Retrospective Studies ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: African women are affected by cancer at an early age of their productivity. However, the exact prevalence and incidence of cancer, including breast cancer is not known in most sub-Saharan African countries, including Ethiopia because of lack of well-established cancer registry. This study aims to assess the epidemiology of breast cancer at Hawassa University Comprehensive Specialized Hospital (HUCSH), the biggest referral hospital with cancer treatment center serving the southern part of the country.

METHODS: Retrospective review of charts of all patients with a diagnosis of breast cancer between 2013 and 2019 at HUCSH was conducted. A standardized questionnaire was used to collect relevant data that include sociodemographic, symptoms, type of diagnosis, treatment, and outcomes. Data were entered using epidata version 3.1 and analyzed using MS Excel and SPSS version 20.

RESULTS: Five hundred fifty-nine (18.6%) breast cancer cases were retrieved in 7 years between 2013 and 2019. Of this, 548 (98%) were women. The median ages of the patents were 38 years. Invasive ductal carcinoma was the leading 309 (55.3%) histologic type followed by 185 (33.1%) lobular carcinoma. One hundred seventy-seven (31.7%) were moderately differentiated and 155 (27.7%) were poorly differentiated. Three hundred seventy-two (66.5%) were advanced breast cancer (Stages III and IV). Trends of breast cancer showed the case load is continuously increasing except with a slight reduction of cases in between 2015 and 2016. The majority were advanced breast cancer occurring at an early age by the time diagnosis made. Invasive ductal carcinomas were the predominant one. The trend also showed a continuous increment of cancer case load. Therefore, cancer registration center establishment, community awareness creation, and intensive early detection strategy are mandatory.}, } @article {pmid34928689, year = {2022}, author = {Shoshani, A and Kor, A}, title = {The mental health effects of the COVID-19 pandemic on children and adolescents: Risk and protective factors.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {14}, number = {8}, pages = {1365-1373}, doi = {10.1037/tra0001188}, pmid = {34928689}, issn = {1942-969X}, mesh = {Child ; Female ; Adolescent ; Humans ; Male ; *Pandemics/prevention & control ; *COVID-19 ; Mental Health ; Protective Factors ; Communicable Disease Control ; }, abstract = {OBJECTIVE: The restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic have led to considerable social isolation, posing significant threats to mental health worldwide. The preventive lockdowns may be especially difficult for children and adolescents, who rely extensively on their daily routines and peer connections for stability and optimal development. However, there is a dearth of longitudinal research examining the mental health and daily life impact of the pandemic among children and adolescents. This study addresses this gap by examining the influence of the COVID-19 pandemic on children and adolescents' mental health and well-being, and potential risk and protective moderators of mental health change.

METHOD: In the present study, 1,537 Israeli children and adolescents (Mage = 13.97; 52% girls) completed a battery of questionnaires in September 2019; before the COVID-19 outbreak and immediately after an 8-week lockdown period when schools reopened in May 2020.

RESULTS: A repeated measures multivariant analysis of variance (MANOVA) revealed significantly greater anxiety, depression, and panic symptoms, increases in video game, Internet and TV screen time use, and decreases in positive emotions, life satisfaction, social media use, and peer support during the pandemic. Participants with higher baseline mental health symptoms showed greater symptoms after the lockdown period. Perceived social support and consistent daily routines were found to act as significant protective factors against symptomatology.

CONCLUSIONS: The results highlight the significant mental health consequences of the pandemic on children and adolescents, and substantiate the significant parents' and peers' roles in children's and adolescents' coping during this global pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid34928417, year = {2022}, author = {Worthmann, A and Bartelt, A}, title = {MALDI MSI for a fresh view on atherosclerotic plaque lipids.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {474}, number = {2}, pages = {185-186}, pmid = {34928417}, issn = {1432-2013}, mesh = {Animals ; Brain/metabolism/pathology ; Humans ; Lipids/*chemistry ; Plaque, Atherosclerotic/*metabolism/*pathology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; }, } @article {pmid34926664, year = {2021}, author = {Zhang, L and Cheng, M and Chen, Y and Zhuang, X and Yang, C and Ji, F and Gao, H and Yang, M and Zhu, T and Li, J and Wang, K}, title = {Visualization positioning-guided biopsy of suspicious breast microcalcifications: a retrospective cohort study.}, journal = {Annals of translational medicine}, volume = {9}, number = {21}, pages = {1620}, pmid = {34926664}, issn = {2305-5839}, abstract = {BACKGROUND: At present, most histological evaluations of microcalcifications without a mass are performed using X-ray guided hook wire localization or vacuum-assisted stereotactic biopsy (VASB), but there are still several limitations to these techniques. Therefore, we designed a visualization positioning technique based on three directions of mammography to accurately locate suspected microcalcifications to guide the biopsy.

METHODS: We retrospectively analyzed consecutive patients with suspicious microcalcifications who underwent visualization positioning-guided biopsy (VPB) from June 1, 2016, to June 1, 2021. The visualization positioning technique was performed using an electronic ruler to measure the vertical distance from the microcalcification core to the vertical lines on mammography.

RESULTS: A total of 133 patients (median age 46 years; range, 22-87 years) who underwent VPB were included in our study. Among the 133 cases of microcalcifications based on pathological results, 104 were benign, 14 were high risk, and 15 were malignant. In 124 (93.2%) patients, microcalcification was confirmed during the first round of VPB specimen analysis. Only 6 (4.5%) and 3 (2.3%) patients underwent second and third extended resections, respectively, as the resected specimens did not contain microcalcifications. Four patients (3.0%) with malignant biopsy results underwent a subsequent operation. Two patients with DCIS underwent mastectomy and sentinel lymph node biopsy because of diffuse calcification. One patient had no residual cancer, and the other was upgraded to invasive ductal carcinoma (IDC). Two patients with IDC underwent breast-conserving surgery and mastectomy with sentinel lymph node biopsy.

CONCLUSIONS: VPB can be used to evaluate breast microcalcifications when a mass is not present, making it an effective diagnostic technique.}, } @article {pmid34926229, year = {2021}, author = {Yu, Y and Wang, R and Deng, J and Zhou, J and Zhou, H and Wang, J}, title = {Invasive micropapillary carcinoma of mixed breast cancer metastasizing to the cervical region and thyroid: report of a rare case.}, journal = {Gland surgery}, volume = {10}, number = {11}, pages = {3141-3146}, pmid = {34926229}, issn = {2227-684X}, abstract = {While the incidence of metastatic breast cancer tumors in the thyroid gland is extremely rare, invasive micropapillary carcinoma (IMPC) of the breast metastasizing to the thyroid gland is even rarer. There are no known reported cases in which both invasive ductal carcinoma-no special type (IDC-NST) and IMPC existed in the breast tissue and where only the latter metastasized into the thyroid gland. This report details the case of a 59-year-old Chinese woman who was first diagnosed with grade 2 IDC-NST of the breast with involvement of 6 axillary lymph nodes in 2015. However, 5 years later, blood tests revealed increased tumor markers. Imaging revealed multiple solid nodules in both sides of the thyroid gland. Total thyroidectomy and bilateral cervical lymph node dissection were performed; the findings showed both IDC-NST and IMPC in the lymph nodes, but only the latter in the thyroid gland. Immunohistochemically, these tumor cells were positive for estrogen receptor (ER), progesterone receptor (PR), GATA binding protein 3 (GATA3), and mammaglobin, but negative for thyroglobulin (TG) and thyroid transcription factor-1 (TTF-1). Ultimately, the patient was diagnosed as having mixed breast cancer with metastatic IMPC in the thyroid gland, and chemotherapy was continued. Apart from the possibility of IDC-NST in breast tissue metastasizing to the thyroid, metastasis of IMPC of the breast must also be taken into consideration, especially when the patient has a history of breast cancer and thyroid nodules. Accurate diagnosis of metastatic breast carcinoma is vital for precise treatment and can improve the prognosis of patients.}, } @article {pmid34925997, year = {2021}, author = {Rana, MK and Rana, APS and Khera, U}, title = {Expression of p53 and p16 in Carcinoma Breast Tissue: Depicts Prognostic Significance or Coincidence.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19395}, pmid = {34925997}, issn = {2168-8184}, abstract = {Breast cancer remains the most common malignancy among the Indian female population. The p16 and p53 genes are frequently mutated in breast cancer. Therefore, we aimed to evaluate the prognostic significance of p16 and p53 overexpression in breast cancer and their correlation with various traditional prognostic parameters. Total of 100 confirmed cases of breast cancers were selected. Patients who underwent chemotherapy treatment were excluded from the study. Estrogen receptor (ER), progesterone receptor (PR), and Her2neu immunohistochemistry were performed. The p16 and p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined. The mean age of carcinoma breast was 53.3+11.6 with age ranging from 28 to 82 years. On histopathological examination, 93% of cases were of invasive ductal cell carcinoma (IDC) with majority of grade I (43%). Only 14% of cases showed positive p53 expression and 19% of cases showed positive p16 expression. P16 was seen in a very significant correlation with p53 expression in all breast carcinoma cases (<0.002). p53 expression showed a positively significant (<0.05) correlation with age and grade III. The p16 expression was seen significantly correlated with low mitotic activity index (MAI) only. The p53 over-expression was seen in worse prognostic factors such as high tumor grade, Her2neu and triple-negative expression suggested its potential role in pathogenesis of carcinoma breast. In addition, high expression of p16 seen in low mitotic count and Her2neu expression also emphasized the role of this biomarker and recommends further molecular-based research.}, } @article {pmid34924083, year = {2022}, author = {Szepsenwol, O and Simpson, JA and Griskevicius, V and Zamir, O and Young, ES and Shoshani, A and Doron, G}, title = {The effects of childhood unpredictability and harshness on emotional control and relationship quality: A life history perspective.}, journal = {Development and psychopathology}, volume = {34}, number = {2}, pages = {607-620}, doi = {10.1017/S0954579421001371}, pmid = {34924083}, issn = {1469-2198}, mesh = {Adult ; Adolescent ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Young Adult ; Longitudinal Studies ; *Emotions ; Minnesota ; }, abstract = {Being able to control oneself in emotionally upsetting situations is essential for good relationship functioning. According to life history theory, childhood exposure to harshness and unpredictability should forecast diminished emotional control and lower relationship quality. We examined this in three studies. In Studies 1 and 2, greater childhood unpredictability (frequent financial, residential, and familial changes), but not harshness (low SES), was associated with lower emotional control in adolescents (N = 1041) and adults (N = 327). These effects were stronger during the participants' reproductive years. Moreover, in Study 2, greater childhood unpredictability was indirectly associated with lower relationship quality through lower emotional control. In study 3, we leveraged the Minnesota Longitudinal Study of Risk and Adaptation (N = 160). Greater early-life unpredictability (ages 0-4) prospectively predicted lower relationship quality at age 32 via lower emotional control at the same age. This relation was serially mediated by less supportive observed early maternal care (ages 1.5-3.5) and insecure attachment representations (ages 19 and 26). Early unpredictability also predicted greater observed emotional distress during conflict interactions with romantic partners (ages 19-36). These findings point to the role of emotional control in mediating the effects of unpredictable childhood environments on relationship functioning in adulthood.}, } @article {pmid34916360, year = {2021}, author = {Avci, O and Tacar, SY and Seber, ES and Yetisyigit, T}, title = {Breast cancer in young and very young women; Is age related to outcome?.}, journal = {Journal of cancer research and therapeutics}, volume = {17}, number = {6}, pages = {1322-1327}, doi = {10.4103/jcrt.JCRT_545_20}, pmid = {34916360}, issn = {1998-4138}, mesh = {Adult ; Age Factors ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/drug therapy/*epidemiology/pathology ; Disease Progression ; Female ; Follow-Up Studies ; Hospitalization/*statistics & numerical data ; Humans ; Medical History Taking ; Ovarian Neoplasms/*epidemiology/pathology ; Prognosis ; Retrospective Studies ; Turkey/epidemiology ; }, abstract = {BACKGROUND: Breast cancer in young women is associated with aggressive biology. We analyzed histopathological and clinical properties of breast cancer patients diagnosed at ≤40 years of age.

METHODS: Breast cancer patients who were admitted between 2015 and 2019 were included. Baseline characteristics of the patients with treatment-related outcomes were assessed. The study group was divided into two subgroups; <35 years old as "very young" and ≥35 years old as "young."

RESULTS: The data of 137 patients (60 patients <35 years) were reviewed. The mean age was 34.7 years. The mean follow-up duration was 44.45 ± 26.39 months, and the mean disease-free survival was 36.17 ± 21.97 months. 11.4% of the patients were diagnosed with Stage 4 disease. Pathologic subtype was invasive ductal carcinoma in 86% of patients. 16.8% of the patients were luminal A, 38.7% luminal B, 30.5% were human epidermal growth factor receptor-2-positive type, and 15.3% were triple-negative. Only 5 (3.3%) patients had given birth after chemotherapy. During the follow-up period of early-staged diagnosed patients, metastatic disease occurred in 24.6%. The rate of distant metastasis development was statistically higher in the very young group (31% vs. 11%; P = 0.004). Thirteen patients (10.7%) died due to disease progression. Thirty-seven percent of the patients had a positive family history for either breast or ovarian cancer.

CONCLUSIONS: Very young breast cancer patients seem to have a more aggressive disease course. The low rate of childbearing in this young patient population is conspicuous. An interdisciplinary approach for the management of this special patient population should be taken into consideration.}, } @article {pmid34916202, year = {2021}, author = {Cai, W and Zhuang, Y and Chen, J and Wang, H}, title = {[Effect of postmastectomy radiotherapy on survival outcomes of patients with metaplastic breast cancer].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {41}, number = {11}, pages = {1733-1740}, pmid = {34916202}, issn = {1673-4254}, mesh = {*Breast Neoplasms/radiotherapy/surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Multivariate Analysis ; Prognosis ; }, abstract = {OBJECTIVE: To evaluate the effect of postmastectomy radiotherapy (PMRT) on the overall survival (OS) and breast cancer-specific survival (BCSS) of patients with metaplastic breast cancer (MpBC) in comparison with those of patients with invasive ductal breast carcinoma (IDC).

METHODS: We selected the patients with pathologically confirmed MpBC and IDC who either received PMRT or not from the archived cases (from January, 1998 to December, 2016) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. In total, 31 982 patients were selected, including 308 patients with MpBC and PMRT, 629 with MpBC and PMRT, and 31 045 with IDC and PMRT. All the included patients were above 18 years of age without distant metastases or a second primary cancer and underwent radical surgery. Baseline characteristics of the patients were compared among the 3 subgroups, and multivariate Cox regression and Kaplan-Meier analyses were performed for analyzing the prognostic factors of MpBC, OS, and BCSS.

RESULTS: The majority (81.2%) of patients with MpBC were older than 50 years, had pathological grade III (68%), and were negative for ER (75.9%) and PR (79.8%) and in stage T2-3 (71.3%) and N0-1 (85.6%). Multivariate Cox regression analysis showed that age, T stage, N stage, PMRT, and chemotherapy were significantly associated with the prognosis of patients with MpBC (P < 0.05), while pathological grade, ER status, or PR status did not significantly affect the prognosis (P>0.05). Kaplan-Meier analysis showed that the patients with MpBC and PMRT had better OS (HR=1.394, 95% CI: 1.125-1.727; P < 0.05) and BCSS (HR=1.390, 95% CI: 1.074-1.800; P < 0.05) than those with MpBC who did not receive PMRT; but after PMRT, the patients with MpBC had worse OS (HR=1.626, 95%CI: 1.386-1.908; P < 0.001) and BCSS (HR=1.710, 95% CI: 1.418-2.062; P < 0.001) as compared with those with IDC.

CONCLUSION: MpBC has unique clinicopathological features. In patients with MpBC, age, T stage, N stage, radiotherapy and chemotherapy are all the prognostic factors affecting the survival outcomes, and PMRT can improve the OS and BCSS of the patients.}, } @article {pmid34899603, year = {2021}, author = {Kopf, S and Kumar, V and Kender, Z and Han, Z and Fleming, T and Herzig, S and Nawroth, PP}, title = {Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {765201}, pmid = {34899603}, issn = {1664-2392}, mesh = {Animals ; DNA Damage/genetics ; Diabetes Complications/blood/*complications/genetics ; Diabetes Mellitus, Type 1/blood/*complications/genetics ; Diabetes Mellitus, Type 2/blood/*complications/genetics ; Humans ; Pulmonary Fibrosis/blood/*etiology/genetics ; }, abstract = {Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.}, } @article {pmid34896356, year = {2022}, author = {Somerville, LAL and List, RP and Compton, MH and Bruschwein, HM and Jennings, D and Jones, MK and Murray, RK and Starheim, ER and Webb, KM and Gettle, LS and Albon, DP}, title = {Real-World Outcomes in Cystic Fibrosis Telemedicine Clinical Care in a Time of a Global Pandemic.}, journal = {Chest}, volume = {161}, number = {5}, pages = {1167-1179}, pmid = {34896356}, issn = {1931-3543}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; *COVID-19/epidemiology ; *Cystic Fibrosis/drug therapy/therapy ; Humans ; Pandemics ; Retrospective Studies ; *Telemedicine ; }, abstract = {BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes.

RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared with in-person clinical care for patients with CF during the COVID-19 pandemic?

STUDY DESIGN AND METHODS: Adults with CF were included. The prepandemic year was defined as March 17, 2019, through March 16, 2020, and the pandemic year (PY) was defined as March 17, 2020, through March 16, 2021. Patients were enrolled starting in the PY. Prepandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included previsit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. FEV1 percent predicted, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/tezacaftor/ivacaftor treatment.

RESULTS: One hundred twenty-four patients participated. One hundred ten patients were analyzed (mean age, 35 years; range, 18-69 years). Ninety-five percent had access to telemedicine (n = 105). Telemedicine visits accounted for 64% of encounters (n = 260), hybrid visits with telemedicine support accounted for 28% of encounters (n = 114), and in-person visits accounted for 7% of encounters (n = 30). No difference in lung function or exacerbation rate during the PY was found. BMI increased from 25 to 26 kg/m[2] (t100 = -4.72; P < .001). Antibiotic use decreased from 316 to 124 episodes (z = 8.81; P < .0001).

INTERPRETATION: This CF care model, which includes IDC-TM, successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests that social mitigation strategies were protective.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04402801; URL: www.

CLINICALTRIALS: gov.}, } @article {pmid34894301, year = {2021}, author = {Mohr, H and Foscarini, A and Steiger, K and Ballke, S and Rischpler, C and Schilling, F and Pellegata, NS}, title = {Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment.}, journal = {EJNMMI research}, volume = {11}, number = {1}, pages = {121}, pmid = {34894301}, issn = {2191-219X}, support = {391523415-SFB824-B8//deutsche forschungsgemeinschaft/ ; 391523415-SFB824-Z02//deutsche forschungsgemeinschaft/ ; 391523415-SFB824-Z03//deutsche forschungsgemeinschaft/ ; 314061271-TRR 205-B11//deutsche forschungsgemeinschaft/ ; }, abstract = {Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.}, } @article {pmid34886276, year = {2021}, author = {Moriano, JA and Molero, F and Laguía, A and Mikulincer, M and Shaver, PR}, title = {Security Providing Leadership: A Job Resource to Prevent Employees' Burnout.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {23}, pages = {}, pmid = {34886276}, issn = {1660-4601}, mesh = {*Burnout, Professional/prevention & control ; Burnout, Psychological ; Female ; Humans ; *Leadership ; Male ; Organizations ; Workplace ; }, abstract = {Leadership styles in work contexts play a role in employees' well-being, contributing to better health or, on the contrary, being a source of stress. In this study we propose that security providing leadership may be considered as a resource to prevent employees' job burnout. First, we examine the relationship between employees' perception of their leader's degree of security in providing leadership and the employees' degree of job-related burnout. Second, the underlying processes by which leaders as security providers exert their influence on burnout are analyzed with a focus on the mediating role of two variables: an organizational climate oriented to psychological safety and organizational dehumanization. A total of 655 Spanish employees (53.7% women) completed a paper-and-pencil self-report questionnaire. To recruit participants, we employed an exponential non-discriminative snowball sampling. Results, using Partial Least Squares Structural Equation Modeling (PLS-SEM) to test hypotheses, show that security providing leadership was related negatively to burnout. Furthermore, psychological safety climate and organizational dehumanization mediated the relationship between security providing leadership and burnout. These findings support the attachment approach to leadership and open new avenues for creating better organizational environments. Security-providing leaders, by supporting employees and treating them in a personalized way, can enhance the psychological safety climate and prevent organizational dehumanization and consequent job burnout.}, } @article {pmid34884926, year = {2021}, author = {Kang, M and Lee, H and Byeon, SJ and Kwon, GY and Jeon, SS}, title = {Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884926}, issn = {1422-0067}, support = {NRF-2020R1A2C2007662//National Research Foundation of Korea/ ; NRF-2020R1C1C1005054//National Research Foundation of Korea/ ; }, mesh = {Animals ; DNA Repair/genetics ; Genomic Instability ; Humans ; Male ; *Mutation ; Precision Medicine ; Prostatic Neoplasms/*genetics/*pathology/therapy ; Xenograft Model Antitumor Assays ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2-ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate-ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.}, } @article {pmid34884498, year = {2021}, author = {Betz, IR and Qaiyumi, SJ and Goeritzer, M and Thiele, A and Brix, S and Beyhoff, N and Grune, J and Klopfleisch, R and Greulich, F and Uhlenhaut, NH and Kintscher, U and Foryst-Ludwig, A}, title = {Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884498}, issn = {1422-0067}, mesh = {Animals ; Cardiomegaly/chemically induced/*drug therapy/metabolism/pathology ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects/metabolism/pathology ; PPAR alpha/genetics/*metabolism ; PPAR delta/genetics/*metabolism ; }, abstract = {Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.}, } @article {pmid34881777, year = {2022}, author = {Sidhanth, C and Bindhya, S and Shabna, A and Krishnapriya, S and Manasa, P and Nagare, RP and Joshua, T and Sneha, S and Murhekar, K and Ganesan, TS}, title = {LASP-1 interacts with ErbB2 in ovarian cancer cells.}, journal = {The Biochemical journal}, volume = {479}, number = {1}, pages = {23-38}, doi = {10.1042/BCJ20210173}, pmid = {34881777}, issn = {1470-8728}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Ovarian Epithelial/*metabolism/pathology ; Cell Line, Tumor ; Cohort Studies ; Cytoskeletal Proteins/genetics/*metabolism ; Female ; HEK293 Cells ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Lapatinib/pharmacology ; Middle Aged ; Ovarian Neoplasms/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Plasmids ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Receptor, ErbB-2/genetics/*metabolism ; Signal Transduction/drug effects/*genetics ; Transfection ; }, abstract = {LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.}, } @article {pmid34881099, year = {2021}, author = {Dudgeon, SN and Wen, S and Hanna, MG and Gupta, R and Amgad, M and Sheth, M and Marble, H and Huang, R and Herrmann, MD and Szu, CH and Tong, D and Werness, B and Szu, E and Larsimont, D and Madabhushi, A and Hytopoulos, E and Chen, W and Singh, R and Hart, SN and Sharma, A and Saltz, J and Salgado, R and Gallas, BD}, title = {A Pathologist-Annotated Dataset for Validating Artificial Intelligence: A Project Description and Pilot Study.}, journal = {Journal of pathology informatics}, volume = {12}, number = {}, pages = {45}, pmid = {34881099}, issn = {2229-5089}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Validating artificial intelligence algorithms for clinical use in medical images is a challenging endeavor due to a lack of standard reference data (ground truth). This topic typically occupies a small portion of the discussion in research papers since most of the efforts are focused on developing novel algorithms. In this work, we present a collaboration to create a validation dataset of pathologist annotations for algorithms that process whole slide images. We focus on data collection and evaluation of algorithm performance in the context of estimating the density of stromal tumor-infiltrating lymphocytes (sTILs) in breast cancer.

METHODS: We digitized 64 glass slides of hematoxylin- and eosin-stained invasive ductal carcinoma core biopsies prepared at a single clinical site. A collaborating pathologist selected 10 regions of interest (ROIs) per slide for evaluation. We created training materials and workflows to crowdsource pathologist image annotations on two modes: an optical microscope and two digital platforms. The microscope platform allows the same ROIs to be evaluated in both modes. The workflows collect the ROI type, a decision on whether the ROI is appropriate for estimating the density of sTILs, and if appropriate, the sTIL density value for that ROI.

RESULTS: In total, 19 pathologists made 1645 ROI evaluations during a data collection event and the following 2 weeks. The pilot study yielded an abundant number of cases with nominal sTIL infiltration. Furthermore, we found that the sTIL densities are correlated within a case, and there is notable pathologist variability. Consequently, we outline plans to improve our ROI and case sampling methods. We also outline statistical methods to account for ROI correlations within a case and pathologist variability when validating an algorithm.

CONCLUSION: We have built workflows for efficient data collection and tested them in a pilot study. As we prepare for pivotal studies, we will investigate methods to use the dataset as an external validation tool for algorithms. We will also consider what it will take for the dataset to be fit for a regulatory purpose: study size, patient population, and pathologist training and qualifications. To this end, we will elicit feedback from the Food and Drug Administration via the Medical Device Development Tool program and from the broader digital pathology and AI community. Ultimately, we intend to share the dataset, statistical methods, and lessons learned.}, } @article {pmid34877215, year = {2021}, author = {Athamnah, M and Rabai, NA and Shkoukani, ZW and Al Azzam, HS and Abu-Shanab, A}, title = {Nipple-Sparing Mastectomy: Initial Experience Evaluating Patients Satisfaction and Oncological Safety in a Tertiary Care Centre in Jordan.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19238}, pmid = {34877215}, issn = {2168-8184}, abstract = {Introduction Nipple-sparing mastectomy (NSM), a procedure involving careful dissection of the breast tissue whilst keeping the nipple-areola complex (NAC) intact, is now increasingly practiced amongst surgeons in the treatment of certain situations of breast cancer. Given the importance of breasts to the female body image, this type of conservative breast surgery takes into account patient satisfaction and overall cosmesis, whilst ensuring appropriate oncological safety. Methods and results Four nipple-sparing mastectomy procedures were performed in our tertiary care centre, Princess Basma Teaching Hospital, in Jordan between June and September 2019. Indications for these procedures included invasive ductal carcinoma, malignant phyllodes, and high-grade ductal carcinoma in-situ. Patients were carefully assessed prior to surgical intervention using radiological imaging, ensuring a distance from NAC of >2 cm in all cases. Procedures were performed successfully with minimal intraoperative and no post-operative complications. Follow-up was carried out at 24 months, with no cases of local or distant post-operative recurrence, and patient satisfaction was qualitatively measured with the use of a BREAST-Q questionnaire. The questionnaire demonstrated improved overall physical well-being and satisfaction with an average overall post-operative physical well-being of 97%. Conclusion Following nipple-sparing mastectomy and immediate submuscular reconstruction with silicone implants,patients demonstrated high levels of satisfaction and quality of life (QoL) as measured by BREAST-Q survey. Two years of follow-up confirmed high patient satisfaction with increased scores from the preoperative baseline level.}, } @article {pmid34877066, year = {2021}, author = {Adrada, BE and Karbasian, N and Huang, M and Rauch, GM and Woodtichartpreecha, P and Whitman, G}, title = {Imaging Surveillance of the Reconstructed Breast in a Subset of Patients May Aid in Early Detection of Breast Cancer Recurrence.}, journal = {Journal of clinical imaging science}, volume = {11}, number = {}, pages = {58}, pmid = {34877066}, issn = {2156-7514}, abstract = {OBJECTIVES: The purpose of this study is to determine the biological markers more frequently associated with recurrence in the reconstructed breast, to evaluate the detection method, and to correlate recurrent breast cancers with the detection method.

MATERIAL AND METHODS: An institutional review board-approved retrospective study was conducted at a single institution on 131 patients treated with mastectomy for primary breast cancer followed by breast reconstruction between 2005 and 2012. Imaging features were correlated with clinical and pathologic findings.

RESULTS: Of the 131 patients who met our inclusion criteria, 40 patients presented with breast cancer recurrence. The most common histopathologic type of primary breast cancer was invasive ductal carcinoma in 82.5% (33/40) of patients. Triple-negative breast cancer was the most common biological marker with 42.1% (16/38) of cases. Clinically, 70% (28/40) of the recurrences presented as palpable abnormalities. Of nine patients who underwent mammography, a mass was seen in eight patients. Of the 35 patients who underwent ultrasound evaluation, an irregular mass was found in 48.6% (17/35) of patients. Nine patients with recurrent breast cancer underwent breast MRI, and MRI showed an irregular enhancing mass in four patients, an oval mass in four patients, and skin and trabecular thickening in one patient. About 55% of patients with recurrent breast cancer were found to have distant metastases.

CONCLUSION: Patients at higher risk for locoregional recurrence may benefit from imaging surveillance in order to detect early local recurrences.}, } @article {pmid34868577, year = {2021}, author = {Aldulaijan, FA and Alsahwan, AG and Alsulaiman, MHA and Mashhour, MM and Alwabari, A}, title = {Histiocytoid variant of invasive lobular breast carcinoma. A case report and literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {72}, number = {}, pages = {103091}, pmid = {34868577}, issn = {2049-0801}, abstract = {INTRODUCTION: Histiocytoid breast carcinoma (HBC) is a variant of invasive lobular carcinoma. The occurrence of HBC is rare and the natural history and clinical course of HBC is still not well known due to limited numbers of reported cases. In reality, many tumors have been misdiagnosed and reported as benign lesions.

CASE PRESENTATION: A 66-year-old- postmenopausal women, who has previous personal history of right breast invasive ductal carcinoma, for which she underwent right breast wide local excision with negative sentinel lymph node biopsy and received adjuvant radiotherapy and hormonal therapy. Two years later, a new left breast suspicious lesion was detected by Imaging. Breast Ultrasound showed left breast hypo-echoic area at 12-1 o'clock with irregular spiculated lesion 3 cm away from the nipple with posterior acoustic shadowing measuring 1 × 0.7 × 0.7 cm and mild tissue distortion with thicken cortical left Axillary lymph node. Mammography of both breasts confirmed the left breast lesion at 12o'clock with necrosis and irregular margins measuring 1.1 × 1.0 cm. MRI breasts showed, left breast heterogeneously enhancing mass at 12 o'clock with no other suspicious mass in the left or right breast. Ultrasound guided left breast biopsy of the suspicious lesion seen at 12-1 o'clock which confirmed the diagnosis of invasive lobular carcinoma, histiocytoid variant She underwent wire guided left breast wide local excision with left sentinel lymph node and axillary clearance. Final histopathology showed invasive lobular carcinoma, histiocytoid variant.

CLINICAL DISCUSSION: The recognition of histiocytoid breast carcinoma is often a challenge, particularly when histiocytoid tumor cells occur in a metastatic site before the primary diagnosis of breast cancer. An awareness of histological features are needed to make the accurate diagnosis.

CONCLUSION: Findings that support the correct diagnosis include identifying tumor cells with more cytological atypia, the presence of cytoplasmic vacuoles and secretions. Moreover, coexistence with invasive lobular carcinoma and/or lobular neoplasia and the use of immunohistochemistry to confirm their epithelial nature. clinico-radiological correlation is essential, as any discordance should trigger further diagnostic determination.}, } @article {pmid34867990, year = {2021}, author = {Teixeira, PC and Ducret, A and Langen, H and Nogoceke, E and Santos, RHB and Silva Nunes, JP and Benvenuti, L and Levy, D and Bydlowski, SP and Bocchi, EA and Kuramoto Takara, A and Fiorelli, AI and Stolf, NA and Pomeranzeff, P and Chevillard, C and Kalil, J and Cunha-Neto, E}, title = {Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {755782}, pmid = {34867990}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Chagas Cardiomyopathy/*metabolism/*physiopathology ; Energy Metabolism/physiology ; Female ; Heart/*physiopathology ; Humans ; Male ; Middle Aged ; Mitochondria/*metabolism/pathology ; Myocardium/*metabolism/pathology ; Young Adult ; }, abstract = {Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.}, } @article {pmid34864494, year = {2022}, author = {O'Connor, DJ and Davey, MG and Barkley, LR and Kerin, MJ}, title = {Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery-A systematic review and meta-analysis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {61}, number = {}, pages = {1-10}, pmid = {34864494}, issn = {1532-3080}, mesh = {*Breast Neoplasms/drug therapy/surgery ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; *Carcinoma, Lobular/drug therapy/surgery ; Female ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; }, abstract = {UNLABELLED: Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins.

BACKGROUND: Neoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences.

AIM: To determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC.

METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P-values <0.05 were statistically significant.

RESULTS: 40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5-3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77-2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87-2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88-8.15] p < 0.00001).

CONCLUSION: This is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.}, } @article {pmid34862071, year = {2022}, author = {Di Lena, É and Hopkins, B and Wong, SM and Meterissian, S}, title = {Delays in operative management of early-stage, estrogen receptor-positive breast cancer during the COVID-19 pandemic: A multi-institutional matched historical cohort study.}, journal = {Surgery}, volume = {171}, number = {3}, pages = {666-672}, pmid = {34862071}, issn = {1532-7361}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/drug therapy/metabolism/*surgery ; *COVID-19 ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*surgery ; Case-Control Studies ; Female ; Humans ; Mastectomy/statistics & numerical data ; Middle Aged ; Neoadjuvant Therapy ; Prospective Studies ; Receptors, Estrogen/metabolism ; Time-to-Treatment/*statistics & numerical data ; }, abstract = {BACKGROUND: During the COVID-19 pandemic, guidelines recommended that breast cancer centers delay estrogen receptor-positive breast cancer surgeries with neoadjuvant endocrine therapy. We aimed to evaluate pathologic upstaging of breast cancer patients affected by these guidelines.

METHODS: Female patients with stage I/II breast cancer receiving neoadjuvant endocrine therapy were prospectively identified and were matched to a historical cohort of stage I/II estrogen receptor-positive breast cancer patients treated with upfront surgery ≤35 days. Primary outcomes were pathologic T and N upstaging versus clinical staging.

RESULTS: After matching, 28 neoadjuvant endocrine therapy and 48 control patients remained. Median age in each group was 65 (P = .68). Most patients (78.6% and 79.2%) had invasive ductal carcinoma with a clinical tumor size of 0.9 cm vs 1.7 cm (P = .056). Time to surgery was 68 days in the neoadjuvant endocrine therapy group and 26.5 days in the control (P < .001). A total of 23 neoadjuvant endocrine therapy patients (82.1%) had the same or lower pT-stage compared with 31 (64.5%) control patients (P = .115). Only 3 (10.7%) neoadjuvant endocrine therapy patients had increased pN-stage vs 14 (29.2%) control patients (P = .063).

CONCLUSION: Despite 2.5-times longer delays, patients with early-stage estrogen receptor-positive breast cancer receiving neoadjuvant endocrine therapy did not experience pathologic upstaging during the COVID-19 pandemic. These findings may support the use of neoadjuvant endocrine therapy in similar patients if delays to surgery are projected.}, } @article {pmid34858260, year = {2021}, author = {Sanilevici, M and Reuveni, O and Lev-Ari, S and Golland, Y and Levit-Binnun, N}, title = {Mindfulness-Based Stress Reduction Increases Mental Wellbeing and Emotion Regulation During the First Wave of the COVID-19 Pandemic: A Synchronous Online Intervention Study.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {720965}, pmid = {34858260}, issn = {1664-1078}, abstract = {The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking mental health support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing and mental health by reducing stress and anxiety and improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar to face-to-face programs. However, the effectiveness of such online-MBIs to support mental health in highly stressful times, such as a global pandemic, requires further study. To this end, we investigated the effect of an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects of mental health during the first wave of the COVID-19 pandemic. Participants (N=92) who expressed interest in discounted online-MBSR programs were recruited for the study. The division into experimental and control groups was based on actual enrollment to the courses. Those who enrolled in a program were assigned to the experimental condition and those who decided not to enroll served as controls. Participants were assessed pre-intervention, post-intervention, and 1-month post-intervention for levels of mindfulness, perceived stress, anxiety, emotion regulation, and intolerance of uncertainty. Differences between the groups were tested using the general linear mixed effects model (GLMM) and Individual Growth Curve Models (IGCM) in intent to treat analysis. The findings indicated that, relative to the control group, MBSR improved mindfulness abilities (p <0.001), decreased anxiety (p <0.001), and stress (p <0.001) and increased emotion regulation (p <0.001). These effects were found to persist 1 month after the end of the program, despite the increased governmental public-health restrictions due to COVID-19 at that time. The ability to tolerate uncertainty, a central characteristic of the pandemic, was not found to be affected by the program. A mediation analysis revealed that the effect of the intervention on mental health improvement was partially mediated by the improvement in emotion regulation. Overall, the findings provide positive evidence for the feasibility of an online-MBSR program to support the mental health of individuals from the general population through the mediation of emotion regulation in challenging times, such as a global pandemic.}, } @article {pmid37197402, year = {2021}, author = {Bashir, S and Loya, A and Tabish, S and Mushtaq, S and Hassan, U and Hussain, M}, title = {Expression of B-cell Lymphoma 2 in Breast Cancer.}, journal = {Journal of cancer & allied specialties}, volume = {7}, number = {1}, pages = {e369}, pmid = {37197402}, issn = {2411-989X}, abstract = {INTRODUCTION: Immunohistochemical expression of B-cell lymphoma 2 (BCL-2) is seen variably in invasive ductal carcinoma. This study was conducted to determine the frequency of BCL-2 expression in different histologic grades of invasive ductal carcinoma.

MATERIALS AND METHODS: A cross-sectional study was conducted in the Department of Pathology at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan, on subjects with invasive ductal carcinoma of various histologic grades. Immunohistochemistry was done using the BCL-2 antibody in all cases. The frequency of BCL-2-positive cases in different histologic grades was noted. Post-stratification, the Chi-square test was applied. P ≤ 0.05 was considered statistically significant.

RESULTS: All 52 subjects were female (100%) with a mean age of 47.58 ± 1.43 years. BCL-2 expression was observed in 28 (53.85 %) subjects with breast cancer. Out of 33 participants with Grade III, 13 (39.39 %) participants were positive for BCL- 2 expression. Among 18 subjects with Grade II, 14 (77.78 %) subjects were positive for BCL-2 expression. Reduced frequency of BCL-2 expression was observed with increasing histologic grade (i.e., more in low-grade tumours and less in Grade III), but the difference was statistically not significant.

CONCLUSION: A differential expression of BCL-2 was observed across different grades of invasive ductal carcinoma. However, the difference was not statistically significant.}, } @article {pmid36238077, year = {2021}, author = {Lee, SY and Woo, OH and Shin, HS and Song, SE and Cho, KR and Seo, BK and Hwang, SY}, title = {Assessment of Additional MRI-Detected Breast Lesions Using the Quantitative Analysis of Contrast-Enhanced Ultrasound Scans and Its Comparability with Dynamic Contrast-Enhanced MRI Findings of the Breast.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {4}, pages = {889-902}, pmid = {36238077}, issn = {2288-2928}, abstract = {PURPOSE: To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) for additional MR-detected enhancing lesions and to determine whether or not kinetic pattern results comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can be obtained using the quantitative analysis of CEUS.

MATERIALS AND METHODS: In this single-center prospective study, a total of 71 additional MR-detected breast lesions were included. CEUS examination was performed, and lesions were categorized according to the Breast Imaging-Reporting and Data System (BI-RADS). The sensitivity, specificity, and diagnostic accuracy of CEUS were calculated by comparing the BI-RADS category to the final pathology results. The degree of agreement between CEUS and DCE-MRI kinetic patterns was evaluated using weighted kappa.

RESULTS: On CEUS, 46 lesions were assigned as BI-RADS category 4B, 4C, or 5, while 25 lesions category 3 or 4A. The diagnostic performance of CEUS for enhancing lesions on DCE-MRI was excellent, with 84.9% sensitivity, 94.4% specificity, and 97.8% positive predictive value. A total of 57/71 (80%) lesions had correlating kinetic patterns and showed good agreement (weighted kappa = 0.66) between CEUS and DCE-MRI. Benign lesions showed excellent agreement (weighted kappa = 0.84), and invasive ductal carcinoma (IDC) showed good agreement (weighted kappa = 0.69).

CONCLUSION: The diagnostic performance of CEUS for additional MR-detected breast lesions was excellent. Accurate kinetic pattern assessment, fairly comparable to DCE-MRI, can be obtained for benign and IDC lesions using CEUS.}, } @article {pmid36238057, year = {2021}, author = {Park, HM and Lim, HS and Ki, SY and Lee, HJ and Lee, JS and Park, MH}, title = {[Invasive Ductal Carcinoma Originating from a Borderline Phyllodes Tumor in a Young Female: A Case Report].}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {4}, pages = {971-976}, pmid = {36238057}, issn = {2288-2928}, abstract = {Phyllodes tumors of the breast are relatively rare fibroepithelial tumors that account for less than 1% of primary breast neoplasms. Phyllodes tumors have epithelial and stromal components and they originate from the periductal stroma. They are classified as benign, borderline, or malignant. Carcinomatous differentiation of the epithelial components of phyllodes tumors is rare, and their imaging features have not been accurately described. Herein, we report a rare case of invasive ductal carcinoma originating from a borderline phyllodes tumor in a 21-year-old female with radiologic and pathologic findings.}, } @article {pmid37117717, year = {2021}, author = {Tzachor, A and Richards, CE and Holt, L}, title = {Future foods for risk-resilient diets.}, journal = {Nature food}, volume = {2}, number = {5}, pages = {326-329}, pmid = {37117717}, issn = {2662-1355}, abstract = {Future foods, such as microalgae, mycoprotein and mealworm, have been suggested as nutritious and sustainable dietary options. Here we consider one of the most profound, yet neglected, benefits of future foods farming systems-their potential to provide essential nutrition in the face of systemic disturbances-and discuss major barriers to realizing this prospect.}, } @article {pmid36238736, year = {2021}, author = {Woo, SH and Jung, HK and Kim, W}, title = {Bilateral Breast Cancer in a Patient with Neurofibromatosis Type 1: A Case Report.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {82}, number = {2}, pages = {417-422}, pmid = {36238736}, issn = {2288-2928}, abstract = {Neurofibromatosis type 1 (NF1) is a rare neuroectodermal disease that is associated with an increased risk of malignancy. Here, we report a rare case of bilateral breast cancer in a 49-year-old woman with NF1 that presented as a microlobulated oval hypoechoic mass and a complex cystic solid mass on sonography. She underwent bilateral mastectomy. The masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ, and a malignant peripheral nerve sheath tumor. We describe the imaging findings, including ultrasonography, CT, and [18]F-fluorodeoxyglucose PET.}, } @article {pmid35423059, year = {2020}, author = {Taware, R and More, TH and Bagadi, M and Taunk, K and Mane, A and Rapole, S}, title = {Lipidomics investigations into the tissue phospholipidomic landscape of invasive ductal carcinoma of the breast.}, journal = {RSC advances}, volume = {11}, number = {1}, pages = {397-407}, pmid = {35423059}, issn = {2046-2069}, abstract = {The need of identifying alternative therapeutic targets for invasive ductal carcinoma (IDC) of the breast with high specificity and sensitivity for effective therapeutic intervention is crucial for lowering the risk of fatality. Lipidomics has emerged as a key area for the discovery of potential candidates owing to its several shared pathways between cancer cell proliferation and survival. In the current study, we performed comparative phospholipidomic analysis of IDC, benign and control tissue samples of the breast to identify the significant lipid alterations associated with malignant transformation. A total of 33 each age-matched tissue samples from malignant, benign and control were analyzed to identify the altered phospholipids by using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS). A combination of univariate and multivariate statistical approaches was used to select the phospholipid species with the highest contribution in group segregation. Furthermore, these altered phospholipids were structurally confirmed by tandem mass spectrometry. A total of 244 phospholipids were detected consistently at quantifiable levels, out of which 32 were significantly altered in IDC of the breast. Moreover, in pairwise comparison of IDC against benign and control samples, 11 phospholipids were found to be significantly differentially expressed. Particularly, LPI 20:3, PE (22:1/22:2), LPE 20:0 and PC (20:4/22:4) were observed to be most significantly associated with IDC tissue samples. Apart from that, we also identified that long-chain unsaturated fatty acids were enriched in the IDC tissue samples as compared to benign and control samples, indicating its possible association with the invasive phenotype.}, } @article {pmid35117367, year = {2020}, author = {Feng, Y and Zhao, X and Lv, S and Xiong, B and Li, Y and Zhang, M}, title = {Long disease-free survival (48 months) in a breast cancer patient with ovarian and pelvic metastasis-a case report.}, journal = {Translational cancer research}, volume = {9}, number = {12}, pages = {7669-7675}, pmid = {35117367}, issn = {2219-6803}, abstract = {Breast cancer is one of the most common malignant tumors in woman. Ovarian and pelvic metastasis in breast cancer are very rare, and the prognosis is often poor. Lacking typical clinical manifestation, misdiagnose is common. We report a case about a middle-aged postmenopausal woman with complaints of finding a left breast mass and irregular vaginal bleeding. Through ultrasound-guided core-needle biopsy of the masses, the patient's final diagnosis was breast cancer with ovarian and pelvic metastasis. The patient received combinations of chemotherapy (intravenous infusion or peritoneal perfusion), radical surgery (gynecological operation and modified radical mastectomy), radiation and endocrine therapy. Forty-eight months follow-up showed that the patient is generally in good condition and had no signs of local recurrence or metastasis. Invasive ductal carcinoma (IDC) of the breast with unilateral ovarian and pelvic metastasis is rare. It is not easy to differentiate from primary ovarian malignant tumor, and the prognosis is generally poor. We chose a combination chemotherapy regimen sensitive to both breast and ovarian tumors for the patient. The therapeutic effect is remarkable. Only a small number of tumor cells were found in pelvic and ovarian tumors. The patient's breast tumors reached pathological complete remission (pCR), which might be the reason for the patient's good prognosis.}, } @article {pmid35019522, year = {2020}, author = {Mishra, S and Kim, ES and Sharma, PK and Wang, ZJ and Yang, SH and Kaushik, AK and Wang, C and Li, Y and Kim, NY}, title = {Tailored Biofunctionalized Biosensor for the Label-Free Sensing of Prostate-Specific Antigen.}, journal = {ACS applied bio materials}, volume = {3}, number = {11}, pages = {7821-7830}, doi = {10.1021/acsabm.0c01002}, pmid = {35019522}, issn = {2576-6422}, abstract = {The increase in the demand and popularity of smart biosensors has brought a novel and innovative concept to develop a diverse range of semen mutual biomarker (i.e., prostate-specific antigen, PSA)-based biodevices for our daily life applications. Using a versatile strategy, here we have developed a next-generation miniaturized capacitive biomarker-based sensor, which facilitates a direct, rapid quantitation and ultrafast detection of prostate-specific antigen (PSA) selectively. To fabricate an affordable PSA biosensor, an interdigitated capacitor (IDC) was functionalized and to detect PSA at concentrations varying from 0.1 to 10 μL/mL, with a response time of 3 s. Moreover, the PSA biosensor showed a high level of selectivity due to the successful probing of the capacitive response-generated biomolecular interactions using external stimuli at the bioelectrode. The resulting IDC-based PSA biosensors are capable of excellent reproducibility and reusability, which are required for real-time biosensing of any targeted biomolecules where low-concentration detection is a key for point-of-care, on-site sensing applications. We anticipate that this research could open exciting opportunities for PSA detection at a low concentration level.}, } @article {pmid35117337, year = {2020}, author = {Ma, XL and Du, Q and Liu, Y and Zhao, RM and Zhang, SY and Zhao, HF}, title = {Histiocytoid breast carcinoma, neither lobular nor ductal? A case report and literature review.}, journal = {Translational cancer research}, volume = {9}, number = {11}, pages = {7372-7378}, pmid = {35117337}, issn = {2219-6803}, abstract = {Histiocytoid breast carcinoma (HBC) is a rare type of breast cancer with controversial histogenesis, which is characterized by abundant foamy cytoplasm, fuzzy cell boundary, linear or annular infiltration, eccentric large irregular nuclei or prominent nucleoli and low mitotic activity. HBC has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. We presented a case of 75-year-old woman with a 5-cm mass in the left breast. The mass was yellow-beige on cut section. HBC was diagnosed including invasive carcinoma (IC) of apocrine differentiation (diameter about 5 mm) which was surrounded by extensive carcinoma in situ (CIS, diameter about 25 mm) of apocrine type, and a 4-mm invasive ductal carcinoma (IDC) in grade II. The distance between HBC and IDC was 4 mm. There was extensive (42 of 43 lymph nodes) metastasis and intravascular tumor emboli. The tumor extended into peripheral nerve. The pathology showed histiocytoid breast carcinoma with a smaller conventional invasive ductal carcinoma in adjacent area. She received a left modified radical mastectomy. However, on the follow-up imaging techniques, the mass showed no response. We discussed the pathology and immunohistochemical finding, and reviewed the literatures. We found that this case was a unique type of HBC.}, } @article {pmid35117292, year = {2020}, author = {Aliyu, UM and Kehinde, A}, title = {Tolerance and outcome of hypofractionated post-mastectomy radiotherapy among elderly breast cancer patients in a specialized center in Nigeria.}, journal = {Translational cancer research}, volume = {9}, number = {11}, pages = {6833-6840}, pmid = {35117292}, issn = {2219-6803}, abstract = {BACKGROUND: The incidence of breast cancer rises dramatically with age, and numerous studies have reported the benefits of post mastectomy radiotherapy in both young and elderly breast cancer patients. The limited numbers of radiotherapy machines and the conventional fractionation schedule which are of long duration make access to radiotherapy more difficult especially among the elderly in Nigeria. Hypo fractionated radiotherapy offers an alternative option (with a shorter duration and comparable side effects and outcomes) to conventional radiotherapy as reported in western literatures. Such studies are grossly lacking in a sub-Saharan African country like Nigeria, hence the need for this study.

METHODS: In this retrospective study, the records of 83 elderly patients with stages II and III breast cancer that were treated with radiotherapy in the Radiotherapy and Oncology Department of UDUTH, Sokoto, Nigeria, from January 2015 to February 2019 were evaluated. Radiotherapy was given at a dose of 45 Gy in 18 fractions of 2.5 Gy to the chest wall and the regional lymph nodes over a period of 3.5 weeks. The end point was freedom from any grade 3 or higher toxicities and disease free survival at 2 years.

RESULTS: Majority, 67 (80.7%) of the 83 patients had invasive ductal carcinoma which were not otherwise specific. About two-thirds of the patients (69.9%) had the disease located in the right breast. After a 24 month follow up, there were no grade 3 or 4 toxicities. Forty-two (50.6%) and 16 (19.2%) patients had grade 2 skin and nausea/vomiting toxicities respectively. Eighty (96.4%) were disease free at 24 months, 3 (3.6%) patients had local recurrence, while 1 (1.2%) had distant metastasis to the lungs. The two years overall survival rate was 90%.

CONCLUSIONS: Hypofractionated radiotherapy in elderly breast cancer patients proved to be comparable to conventional radiotherapy in terms of toxicities and outcome in our center.}, } @article {pmid35117209, year = {2020}, author = {Lian, W and Zheng, J and Chen, D}, title = {Different prognosis by subtype in the early mucinous breast cancer: a SEER population-based analysis.}, journal = {Translational cancer research}, volume = {9}, number = {10}, pages = {5969-5978}, pmid = {35117209}, issn = {2219-6803}, abstract = {BACKGROUND: Our study aims to investigate the clinicopathological characteristics and survival outcomes of mucinous breast cancer (MBC), and explore the effect of histology type on the breast cancer-specific survival (BCSS) by different subtypes.

METHODS: we identified 7,083 patients who were diagnosed with MBC and 248,751 with infiltrating ductal carcinoma (IDC) by using the Surveillance, Epidemiology and End Results (SEER) database. The propensity score matching was used to match baseline characteristics among MBC and IDC, and multivariable cox proportional hazards models were used to analyze the relationship between histology type stratified by subtype and BCSS.

RESULTS: MBC patients were associated with a fewer nodal involvement, lower grade, earlier stage, more estrogen receptor (ER) or progesterone receptor (PR) positive, and more favorable prognosis compared to the overall IDC population. After 1:1 matching of MBC with IDC by other factors, we found that MBC patients presented better prognosis than the Matched IDC for BCSS. Analysis among ER+PR+ subgroup revealed that MBC patients was significantly better than that Matched IDC patients for BCSS (HR =0.78, 95% CI, 0.63-0.96). However, the survival analysis in the ER+PR- or ER-PR- subgroups suggested that no significant difference was seen between MBC patients and matched IDC patients for BCSS.

CONCLUSIONS: Our findings support that MBC seems to be an independent factor for the better prognosis for breast cancer patients with ER+PR+ breast cancer but not in those with ER+PR- or ER-PR- disease.}, } @article {pmid35518232, year = {2020}, author = {Lee, CP and Karyappa, R and Hashimoto, M}, title = {3D printing of milk-based product.}, journal = {RSC advances}, volume = {10}, number = {50}, pages = {29821-29828}, pmid = {35518232}, issn = {2046-2069}, abstract = {We developed a method to perform direct ink writing (DIW) three-dimensional (3D) printing of milk products at room temperature by changing the rheological properties of the printing ink. 3D printing of food products has been demonstrated by different methods such as selective laser sintering (SLS) and hot-melt extrusion. Methods requiring high temperatures are, however, not suitable to creating 3D models consisting of temperature-sensitive nutrients. Milk is an example of such foods rich in nutrients such as calcium and protein that would be temperature sensitive. Cold-extrusion is an alternative method of 3D printing, but it requires the addition of rheology modifiers and the optimization of the multiple components. To address this limitation, we demonstrated DIW 3D printing of milk by cold-extrusion with a simple formulation of the milk ink. Our method relies on only one milk product (powdered milk). We formulated 70 w/w% milk ink and successfully fabricated complex 3D structures. Extending our method, we demonstrated multi-material printing and created food with various edible materials. Given the versatility of the demonstrated method, we envision that cold extrusion of food inks will be applied in creating nutritious and visually appealing food, with potential applications in formulating foods with various needs for nutrition and materials properties, where food inks could be extruded at room temperature without compromising the nutrients that would be degraded at elevated temperatures.}, } @article {pmid36238615, year = {2020}, author = {Lee, DH and Yoon, RG and An, JK and Woo, JJ}, title = {Ultrasonographic Features and the Diagnostic Role of Core Needle Biopsy at Metastatic Breast Cancer in the Thyroid gland: A Case Report.}, journal = {Taehan Yongsang Uihakhoe chi}, volume = {81}, number = {3}, pages = {719-725}, pmid = {36238615}, issn = {2288-2928}, abstract = {Metastases to the thyroid gland have rarely been reported in clinical settings, and the thyroid gland is an uncommon site for breast carcinoma metastasis. We report a case of a 64-year-old breast cancer patient diagnosed with metastatic breast carcinoma in the thyroid gland after performing ultrasonography (US)-guided core needle biopsy (CNB) and subsequent total thyroidectomy. On US, the thyroid lesion appeared to be mildly enlarged with multiple internal hypoechoic lines and a few microcalcifications without mass formation. Under US-guidance, CNB was performed by targeting the area with microcalcifications and subsequently diagnosed as metastatic breast carcinoma. Total thyroidectomy revealed that the patient had metastatic invasive ductal carcinoma of the breast with lymphatic spread involving both lobes and the isthmus of the thyroid gland. Although the thyroid gland is an uncommon metastatic site, the unusual features of thyroid metastasis can be observed on US; thus, US-guided CNB effectively aids the diagnosis of thyroid metastasis.}, } @article {pmid36133137, year = {2019}, author = {Amiri, A and Hastert, F and Stühn, L and Dietz, C}, title = {Structural analysis of healthy and cancerous epithelial-type breast cells by nanomechanical spectroscopy allows us to obtain peculiarities of the skeleton and junctions.}, journal = {Nanoscale advances}, volume = {1}, number = {12}, pages = {4853-4862}, pmid = {36133137}, issn = {2516-0230}, abstract = {The transition of healthy epithelial cells to carcinoma is associated with an alteration in the structure and organization of the cytoskeleton of the cells. A comparison of the mechanical properties of cancerous and healthy cells indicated a higher deformability of the cancer cells based on averaging the mechanical properties of single cells. However, the exact reason for softening of the cancerous cells compared to their counterparts remains unclear. Here, we focused on nanomechanical spectroscopy of healthy and cancerous ductal epithelial-type breast cells by means of atomic force microscopy with high lateral and depth precision. As a result, based on atomic force microscopy measurements formation of significantly fewer microtubules in cancerous cells which was observed in our study is most likely one of the main causes for the overall change in mechanical properties without any phenotypic shift. Strikingly, in a confluent layer of invasive ductal carcinoma cells, we observed the formation of cell-cell junctions that have the potential for signal transduction among neighboring cells such as desmosomes and adherens junctions. This increases the possibility of cancerous cell collaboration in malignancy, infiltration or metastasis phenomena.}, } @article {pmid35117128, year = {2019}, author = {Botti, G and Cantile, M and Collina, F and Cerrone, M and Sarno, S and Anniciello, A and Di Bonito, M}, title = {Morphological and pathological features of basal-like breast cancer.}, journal = {Translational cancer research}, volume = {8}, number = {Suppl 5}, pages = {S503-S509}, pmid = {35117128}, issn = {2219-6803}, abstract = {Basal-like breast cancer (BLBC) is characterized by high grade, high mitotic indices, presence of central necrotic or fibrotic zones, and lymphocytic infiltrate. Patients presenting with BLBC have a poor prognosis and a short-term disease-free and overall survival. BLBCs may include different histological types of breast cancers but the most common histological type is represented by invasive ductal carcinomas of no special type (IDC-NST). Typical immunohistochemical markers for these tumors are basal-type cytokeratin markers such as CK5/6, CK14, CK17, but several BLBCs also express luminal-type CKs, such as CK8/18, CK19. Different molecular alterations, including BRCA1 dysfunction, p53 mutations, up-regulation of EGFR, inactivation of PTEN and the aberrant expression of many non-coding RNAs molecules are detected in BLBC cells suggesting the possibility of defining new targeted therapeutic strategies for this tumor type.}, } @article {pmid35116851, year = {2019}, author = {Yang, Y and Liu, G and Qin, L and Ye, L and Zhu, F and Ying, Y}, title = {Overexpression of UHRF1 and its potential role in the development of invasive ductal breast cancer validated by integrative bioinformatics and immunohistochemistry analyses.}, journal = {Translational cancer research}, volume = {8}, number = {4}, pages = {1086-1096}, pmid = {35116851}, issn = {2219-6803}, abstract = {BACKGROUND: Increasing evidence has highlighted the role of ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) in the development of cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. However, the correlation between UHRF1 and breast cancer remains unclear. The present study aimed to analyze the expression of UHRF1 and its role in the development of invasive ductal breast cancer (IDC) by integrating multilevel expression data and immunohistochemistry analysis.

METHODS: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to gather UHRF1 expression data on IDC. Additionally, immunohistochemistry analysis was used to investigate the correlations between UHRF1 expression and the clinical characteristics of IDC.

RESULTS: The GEO and TCGA databases indicated that UHRF1 was up-regulated in IDC. Consistently, the immunohistochemical specimens showed that the significant overexpression of UHRF1 in IDC, and its expression level showed an increasing trend from ductal carcinomas in situ to IDC. Notably, the increased levels of UHRF1 were closely correlated with estrogen receptor expression, pathological grade, and the prognosis of the disease. In addition, patients with a high UHRF1 expression had a poorer prognosis.

CONCLUSIONS: In conclusion, our findings suggested that UHRF1 plays a promoting role in breast tumorigenesis, and the over-expression of UHRF1 could serve as a biomarker for the prognosis in invasive ductal carcinomas in breast cancer.}, } @article {pmid35316897, year = {2022}, author = {Budzik, MP and Sobieraj, MT and Sobol, M and Patera, J and Czerw, A and Deptała, A and Badowska-Kozakiewicz, AM}, title = {Medullary breast cancer is a predominantly triple-negative breast cancer - histopathological analysis and comparison with invasive ductal breast cancer.}, journal = {Archives of medical science : AMS}, volume = {18}, number = {2}, pages = {432-439}, pmid = {35316897}, issn = {1734-1922}, abstract = {INTRODUCTION: Medullary breast cancer (MdBC) is an uncommon type of breast cancer representing 1-7% of all cases. It is characterized by the occurrence of many histopathological features associated with a high grade of malignancy.

MATERIAL AND METHODS: Twelve MdBCs chosen from a group of 1,122 women suffering from invasive breast cancer were analyzed. Histopathological examination and analysis of a basic molecular profile, i.e. estrogen (ER), progesterone (PR) and HER2 receptor expression, and their comparison with invasive ductal breast cancer (IDC), were performed.

RESULTS: MdBC accounted for 1.07% of all analyzed invasive breast cancer patients. All patients were female, with an average age of 58.54 years. The MdBC group exhibited a larger median tumor diameter (2.05 vs. 1.89 cm), although ≥ T2 tumors comprised 42% vs. 51% for IDCs. Women without regional lymph node involvement (pN0) (83%) formed the largest group. There was a statistically significant difference in the presence of nodal involvement between the studied groups (p < 0.001). Based on the histological grade of malignancy, the majority of MdBC comprised grade II tumors (G2) (93%). In general, MdBC showed statistically higher histologic grade (G1-G3) than IDC (p = 0.003). The 5-year overall survival rate of MdBC patients was 91%. Most MdBCs (92%) were triple-negative, whereas the remaining 8% were HER2 positive.

CONCLUSIONS: MdBC presented at a younger age than IDC, had a higher histological grade, larger median size and less frequent regional lymph node involvement. Most MdBCs were triple-negative, whereas IDCs were predominantly luminal. Despite numerous aggressive pathological features of MdBC, its clinical outcome and overall prognosis are favorable.}, } @article {pmid36338780, year = {2019}, author = {Lam, JC and Gregson, DB and Robinson, S and Somayaji, R and Welikovitch, L and Conly, JM and Parkins, MD}, title = {Infectious diseases consultation improves key performance metrics in the management of Staphylococcus aureus bacteremia: A multicentre cohort study.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {4}, number = {1}, pages = {24-32}, pmid = {36338780}, issn = {2371-0888}, abstract = {BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. We sought to identify factors associated with infectious diseases consultation (IDC) and understand how IDC associates with SAB patient management and outcomes.

METHODS: A multicentre retrospective study was performed between 2012 and 2014 in a large Canadian Health Zone in order to determine factors associated with IDC and performance of key quality of care determinants in SAB management and clinical outcomes. Factors subject to quality of care determinants were established a priori and studied for associations with IDC and 30-day all-cause mortality using multivariable analysis.

RESULTS: Of 961 SAB episodes experienced by 892 adult patients, 605 episodes received an IDC. Patients receiving IDC were more likely to have prosthetic valves and joints and to have community-acquired and known sources of SAB, but increasing age decreased IDC occurrence. IDC was the strongest independent predictor for quality of care performance metrics, including repeat blood cultures and echocardiography. Mortality at 30 days was 20% in the cohort, and protective factors included IDC, achievement of source control, targeted therapy within 48 hours, and follow-up blood cultures but not the performance of echocardiography.

CONCLUSIONS: There were significant gaps between the treatments and investigations that patients actually received for SAB and what is considered the optimal management of their condition. IDC is associated with improved attainment of targeted SAB quality of care determinants and reduced mortality rates. Based on our findings, we propose a policy of mandatory IDC for all cases of SAB to improve patient management and outcomes.}, } @article {pmid35542123, year = {2018}, author = {Taunk, K and Taware, R and More, TH and Porto-Figueira, P and Pereira, JAM and Mohapatra, R and Soneji, D and Câmara, JS and Nagarajaram, HA and Rapole, S}, title = {A non-invasive approach to explore the discriminatory potential of the urinary volatilome of invasive ductal carcinoma of the breast.}, journal = {RSC advances}, volume = {8}, number = {44}, pages = {25040-25050}, pmid = {35542123}, issn = {2046-2069}, abstract = {Worldwide, breast invasive ductal carcinoma (IDC) accounts for the majority of the reported cases of this form of cancer. IDC effective management, as for any form of cancer, would greatly benefit from early diagnosis. This, however, due to various socio-economic reasons, is very far for the reality in developing countries like India, where cancer diagnosis is often carried out at late stages when disease management is troublesome. With the present work, we aim to evaluate a simple analytical methodology to identify a set of volatile organic compounds (VOCs) in urine samples, as a biosignature for IDC. Using solid-phase microextraction followed by gas chromatography/mass spectrometry, a panel of 14 urinary VOCs was found to discriminate IDC (n = 65) from a healthy control (HC) group (n = 70) through multivariate statistical treatments. Furthermore, metabolic pathway analysis revealed various dysregulated pathways involved in IDC patients hinting that their detailed investigations could lead to novel mechanistic insights into the disease pathophysiology. In addition, we validated the expression pattern of five of these VOCs namely 2-ethyl-1-hexanol, isolongifolenone, furan, dodecanoic acid, 2-methoxy-phenol in another external cohort of 59 urinary samples (IDC = 32 and HC = 27) and found their expression pattern to be consistent with the primary sample set. To our knowledge, this is the first study exploring breast IDC volatome alterations in Indian patients.}, } @article {pmid35540134, year = {2018}, author = {Irshad, M and Mujahid, A and Afzal, A and Bajwa, SZ and Hussain, T and Zaman, WU and Latif, U and Athar, MM}, title = {A miniaturized electronic sensor for instant monitoring of ethanol in gasohol fuel blends.}, journal = {RSC advances}, volume = {8}, number = {41}, pages = {22952-22962}, pmid = {35540134}, issn = {2046-2069}, abstract = {Gasoline-ethanol (gasohol) fuel blends have gained considerable attention in the petroleum and energy sectors as relatively cheaper and greener high-octane alternative fuels with gasoline-comparable efficiency in modern transportation vehicles. However, due to different combustion rates the relative concentration of ethanol in gasohol fuel blends may vary over time. Furthermore, there is a need to monitor ethanol concentration in fuel blends for quality control applications. This article reports a miniaturized electronic sensor based on an interdigital capacitor (IDC) as the transducer and a dual-imprinted titania-polyaniline composite film as the receptor. The device has an active surface area of 0.9 cm[2] and is easy to fabricate. The receptor material is synthesized by imprinting ethanol in both titania sol (EITS, the matrix) and polyaniline nanoparticles (EIPani, the filler), and subsequently mixing them to obtain a dual-imprinted EITS-EIPani composite. The structural and morphological characteristics of the receptor layers are determined with Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM), respectively. The IDC devices are fabricated with pristine EITS and dual-imprinted EITS-EIPani composite to test their metrological sensor characteristics in standard ethanol solutions and real-time gasohol fuel blends. The instant shift in capacitance is measured upon exposure to different concentrations of ethanol. These devices show excellent sensitivity and selectivity patterns and demonstrate reliable sensor response toward ethanol in different gasohol fuel blends with 1-10 vol% ethanol. The results of this study reveal that these miniaturized ethanol sensors are potentially useful for rapid analysis of ethanol in gasohol and may be optimized for onboard fuel quality control applications.}, } @article {pmid34854982, year = {2022}, author = {Highton, PJ and March, DS and Churchward, DR and Grantham, CE and Young, HML and Graham-Brown, MPM and Estruel, S and Martin, N and Brunskill, NJ and Smith, AC and Burton, JO and Bishop, NC}, title = {Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients.}, journal = {European journal of applied physiology}, volume = {122}, number = {3}, pages = {599-609}, pmid = {34854982}, issn = {1439-6327}, support = {CS-2013-13-014//NIHR/ ; DRF-2016-09-015//NIHR/ ; }, mesh = {Biomarkers/*blood ; Cell-Derived Microparticles/*metabolism ; Exercise Therapy/*methods ; Humans ; Inflammation/*blood ; Kidney Failure, Chronic/*blood/*rehabilitation/therapy ; Male ; Middle Aged ; Phenotype ; Renal Dialysis ; }, abstract = {PURPOSE: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients.

METHODS: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays.

RESULTS: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ[2] ≤ 0.399) other than TNF-α (p = 0.001, ηρ[2] = 0.186), though no significance was revealed upon post hoc analysis.

CONCLUSION: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this.

TRIAL REGISTRATION: ISRCTN1129707, prospectively registered on 05/03/2015.}, } @article {pmid34853710, year = {2021}, author = {Husain, S and Isa, M and Almarzooq, R}, title = {A Rare Metastatic Site of Invasive Lobular Breast Carcinoma: A Case Report.}, journal = {Case reports in surgery}, volume = {2021}, number = {}, pages = {9922296}, pmid = {34853710}, issn = {2090-6900}, abstract = {Here, we report a case of a 42-year-old female patient with left lobular breast cancer-gastric metastasis (initially misdiagnosed five years ago as an invasive ductal carcinoma) presenting with dyspepsia, weight loss, and persistent vomiting lasting for four weeks. Upper GI endoscopy revealed evidence of linitis plastica, and histological and immunocytochemical analyses of the biopsy confirmed gastric metastasis secondary to invasive lobular breast carcinoma.}, } @article {pmid34851990, year = {2021}, author = {D'Amora, P and Silva, IDCG and Budib, MA and Ayache, R and Silva, RMS and Silva, FC and Appel, RM and Júnior, SS and Pontes, HBD and Alvarenga, AC and Arima, EC and Martins, WG and Silva, NLF and Diaz, RS and Salzgeber, MB and Palma, AM and Evans, SS and Nagourney, RA}, title = {Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0259909}, pmid = {34851990}, issn = {1932-6203}, support = {UL1 TR001414/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Area Under Curve ; COVID-19/mortality/*pathology/virology ; Carnitine/metabolism ; Citrulline/metabolism ; Female ; Glutamic Acid/metabolism ; Humans ; Kynurenine/metabolism ; Male ; *Metabolome ; Metabolomics/*methods ; Middle Aged ; Ornithine/metabolism ; ROC Curve ; Risk Factors ; SARS-CoV-2/isolation & purification ; Severity of Illness Index ; Tryptophan/metabolism ; }, abstract = {This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.}, } @article {pmid34847802, year = {2022}, author = {Khanam, R and Fleischer, TC and Boghossian, NS and Nisar, I and Dhingra, U and Rahman, S and Fox, AC and Ilyas, M and Dutta, A and Naher, N and Polpitiya, AD and Mehmood, U and Deb, S and Choudhury, AA and Badsha, MB and Muhammad, K and Ali, SM and Ahmed, S and Hickok, DE and Iqbal, N and Juma, MH and Quaiyum, MA and Boniface, JJ and Yoshida, S and Manu, A and Bahl, R and Jehan, F and Sazawal, S and Burchard, J and Baqui, AH}, title = {Performance of a validated spontaneous preterm delivery predictor in South Asian and Sub-Saharan African women: a nested case control study.}, journal = {The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians}, volume = {35}, number = {25}, pages = {8878-8886}, doi = {10.1080/14767058.2021.2005573}, pmid = {34847802}, issn = {1476-4954}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Infant, Newborn ; Female ; Humans ; *Premature Birth/diagnosis ; Case-Control Studies ; Artificial Intelligence ; Prospective Studies ; Biomarkers ; Africa South of the Sahara ; }, abstract = {OBJECTIVES: To address the disproportionate burden of preterm birth (PTB) in low- and middle-income countries, this study aimed to (1) verify the performance of the United States-validated spontaneous PTB (sPTB) predictor, comprised of the IBP4/SHBG protein ratio, in subjects from Bangladesh, Pakistan and Tanzania enrolled in the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, and (2) discover biomarkers that improve performance of IBP4/SHBG in the AMANHI cohort.

STUDY DESIGN: The performance of the IBP4/SHBG biomarker was first evaluated in a nested case control validation study, then utilized in a follow-on discovery study performed on the same samples. Levels of serum proteins were measured by targeted mass spectrometry. Differences between the AMANHI and U.S. cohorts were adjusted using body mass index (BMI) and gestational age (GA) at blood draw as covariates. Prediction of sPTB < 37 weeks and < 34 weeks was assessed by area under the receiver operator curve (AUC). In the discovery phase, an artificial intelligence method selected additional protein biomarkers complementary to IBP4/SHBG in the AMANHI cohort.

RESULTS: The IBP4/SHBG biomarker significantly predicted sPTB < 37 weeks (n = 88 vs. 171 terms ≥ 37 weeks) after adjusting for BMI and GA at blood draw (AUC= 0.64, 95% CI: 0.57-0.71, p < .001). Performance was similar for sPTB < 34 weeks (n = 17 vs. 184 ≥ 34 weeks): AUC = 0.66, 95% CI: 0.51-0.82, p = .012. The discovery phase of the study showed that the addition of endoglin, prolactin, and tetranectin to the above model resulted in the prediction of sPTB < 37 with an AUC= 0.72 (95% CI: 0.66-0.79, p-value < .001) and prediction of sPTB < 34 with an AUC of 0.78 (95% CI: 0.67-0.90, p < .001).

CONCLUSION: A protein biomarker pair developed in the U.S. may have broader application in diverse non-U.S. populations.}, } @article {pmid34846777, year = {2022}, author = {Kamal, AM and Pal, UM and Kumar, A and Das, GR and Pandya, HJ}, title = {Toward the development of portable light emitting diode-based polarization spectroscopy tools for breast cancer diagnosis.}, journal = {Journal of biophotonics}, volume = {15}, number = {3}, pages = {e202100282}, doi = {10.1002/jbio.202100282}, pmid = {34846777}, issn = {1864-0648}, mesh = {Biopsy ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Pilot Projects ; Spectrum Analysis ; }, abstract = {A robust, affordable and portable light emitting diode-based diagnostic tools (POLS-NIRDx) using a polarization-sensitive (linear as well as circular polarization) technique were designed and developed to quantify the degree of linear polarization (DOLP), degree of circular polarization (DOCP). The study was performed on malignant (invasive ductal carcinoma) and adjacent normal ex-vivo biopsy tissues excised from N = 10 patients at the operating wavelengths of 850 and 940 nm. The average DOLP and DOCP values were lower for malignant than adjacent normal while operating at 850 and 940 nm. The highest accuracy was observed for DOLP (100%) and DOCP (80%) while operating at 850 nm, which reduced (80% for DOLP and 65% for DOCP) at 940 nm. This pilot study can be utilized as a differentiating factor to delineate malignant tissues from adjacent normal tissues.}, } @article {pmid34841287, year = {2021}, author = {Erener, S and Ellis, CE and Ramzy, A and Glavas, MM and O'Dwyer, S and Pereira, S and Wang, T and Pang, J and Bruin, JE and Riedel, MJ and Baker, RK and Webber, TD and Lesina, M and Blüher, M and Algül, H and Kopp, JL and Herzig, S and Kieffer, TJ}, title = {Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.}, journal = {Cell reports. Medicine}, volume = {2}, number = {11}, pages = {100434}, pmid = {34841287}, issn = {2666-3791}, support = {//CIHR/Canada ; }, mesh = {Animals ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; Diet, High-Fat ; *Disease Progression ; *Gene Deletion ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism/*pathology ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Organ Specificity ; Pancreatic Neoplasms/*genetics/*pathology ; Rats ; }, abstract = {miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras[G12D];Ptf1a[CreER] reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.}, } @article {pmid34841014, year = {2021}, author = {Beltran-Bless, A and Murshed, M and Zakikhani, M and Kuchuk, I and Bouganim, N and Robertson, S and Kekre, N and Vandermeer, L and Li, J and Addison, CL and Rauch, F and Clemons, M and Kremer, R}, title = {Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients.}, journal = {Bone reports}, volume = {15}, number = {}, pages = {101145}, pmid = {34841014}, issn = {2352-1872}, abstract = {BACKGROUND: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm "Bordier" core needle. We examined the feasibility of using a 2 mm "Jamshidi™" core needle as a more practical and less invasive technique.

METHODS: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry.

RESULTS: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size.

DISCUSSION: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.}, } @article {pmid34837348, year = {2022}, author = {Price, J}, title = {12-year review of MRI-detected breast cancers. How often was a diagnosis of malignancy established using targeted ultrasound and standard 14-gauge core biopsy?.}, journal = {Journal of medical imaging and radiation oncology}, volume = {66}, number = {6}, pages = {738-748}, doi = {10.1111/1754-9485.13352}, pmid = {34837348}, issn = {1754-9485}, mesh = {Australia ; Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnostic imaging/pathology ; *Calcinosis ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging ; Mammography ; Retrospective Studies ; }, abstract = {INTRODUCTION: This retrospective study aimed to determine the percentage of MRI-detected breast cancers diagnosed using targeted ultrasound and standard 14-gauge (14g) biopsy in the setting of an Australian breast MRI service. This is of clinical relevance because malignancies not identifiable on mammography or by ultrasound may then require more invasive, technically demanding and costly MRI-guided interventional procedures, usually by large-core vacuum-assisted biopsy (VAB) or hook-wire localisation with open surgical biopsy.

METHODS: On review of the 12-year period 2006-2018, we identified 67 new breast cancer events in 64 women where the diagnosis was made on the basis of the MRI scan findings either alone (n = 60) or in combination with a concurrent mammogram (n = 7), with no recorded clinical abnormality. The percentage in which malignancy was confirmed on histopathology using targeted ultrasound in combination with 14g biopsy was determined versus other biopsy methods, for both invasive cancer and in situ disease.

RESULTS: Ultrasound-guided 14g biopsy was successful in establishing the presence of malignancy in 42/46 (91%) of events with a final diagnosis of invasive cancer, with 2 more proven by MRI-guided interventional procedures (1 VAB and 1 hook-wire) and 1 by open surgical biopsy. In the final case, a 5 mm focus on MRI with no sonographic correlate at the initial presentation was only identified and biopsied by ultrasound at 12-month follow-up. For events with a final diagnosis of DCIS/pLCIS (pleomorphic LCIS, n = 2), US-guided 14g biopsy was successful in 10/21 (48%), while 4/7 events with corresponding mammographic microcalcifications were proven by x-ray stereotactic interventions. A further 5 events had MRI-guided interventions (3 VAB and 2 hook-wires) and 1 an open surgical biopsy to confirm malignancy. In the final case (a woman with a 30 × 20 mm focal area of non-mass enhancement with corresponding microcalcifications consistent with DCIS), a pathologic diagnosis was not made until the patient presented 5 years later with invasive disease. There were also 3 instances of upgrades to invasion on final surgical pathology, one from pLCIS to microinvasion and 2 others from DCIS to IDC. Among the DCIS/pLCIS events, semi-random 14g core biopsy (sampling at the expected location of the MRI abnormality without a specific sonographic correlate) proved to be successful in 3 women.

CONCLUSION: Ultrasound-guided 14g core biopsy established a malignant diagnosis in 91% of invasive cancers and in 48% of DCIS/pLCIS cases. This relatively non-invasive, technically easy to perform and low-cost biopsy procedure can be used immediately when targeted ultrasound shows a correlate for a suspicious MRI scan finding. Careful imaging-pathologic correlation is required after 14g biopsy, and a discordant result will usually prompt recourse to an MRI-guided VAB or hook-wire localisation.}, } @article {pmid34831010, year = {2021}, author = {Keller, CR and Hu, Y and Ruud, KF and VanDeen, AE and Martinez, SR and Kahn, BT and Zhang, Z and Chen, RK and Li, W}, title = {Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells.}, journal = {Cancers}, volume = {13}, number = {22}, pages = {}, pmid = {34831010}, issn = {2072-6694}, support = {N/A//Washington State University/ ; N/A//Elsa U. Pardee Foundation/ ; }, abstract = {Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.}, } @article {pmid34829743, year = {2021}, author = {Liu, PF and Shu, CW and Yang, HC and Lee, CH and Liou, HH and Ger, LP and Tzeng, YT and Wang, WC}, title = {Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.}, journal = {Biomedicines}, volume = {9}, number = {11}, pages = {}, pmid = {34829743}, issn = {2227-9059}, support = {MOST 108-2320-B-037-038, MOST 109-2320-B-037-015-MY3//The Ministry of Science and Technology/ ; KMU-Q109008; KMU-Q110002//Kaohsiung Medical University Research Foundation/ ; NSYSUKMU 109-I007; NSYSUKMU-110-I006//The National Sun Yat-sen University-KMU Joint Research Project/ ; KMU-TC108A04//Kaohsiung Medical University Research Center Grant/ ; VGHKS106-015; VGHKS107-014//Kaohsiung Veterans General Hospital/ ; }, abstract = {Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.}, } @article {pmid34825721, year = {2022}, author = {Kulali, F and Guner, G}, title = {Outcomes in Sonographically Categorized Complex Cystic Breast Lesions.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {41}, number = {8}, pages = {2071-2077}, doi = {10.1002/jum.15891}, pmid = {34825721}, issn = {1550-9613}, mesh = {Breast/diagnostic imaging/pathology ; *Breast Neoplasms/diagnostic imaging/pathology ; *Cysts/diagnostic imaging ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Ultrasonography ; }, abstract = {OBJECTIVES: To investigate outcomes of patients with complex cystic breast lesions and to determine malignancy rates for each sonographic category.

MATERIAL AND METHODS: A total of 124 women with a mean age of 45 were enrolled in this retrospective study. Complex cysts were classified into four categories according to sonographic findings (thick septa/wall, intramural nodule, solid/cystic ratio) by two radiologists. Size, margin, short-to-long axis ratio, and vascularity were also noted. The relationship between sonographic features and histopathological/follow-up results was evaluated.

RESULTS: Of 124 complex cysts, 11 were malignant and 113 were benign. There were 31 with thick septa/wall (category 1), 14 with intramural nodule (category 2), 60 with solid/cystic ratio < 1 (category 3), and 19 with solid/cystic ratio > 1 (category 4). Among 11 malignant tumors, six intraductal papillary carcinomas and three invasive ductal carcinomas were in category 3, whereas one invasive ductal carcinoma was in category 1 and one was in category 4. Most of malignant lesions (9/11, 82%) were in category 3. Most of benign lesions (96/113, 85%) were fibroadenomatoid/fibrocystic changes. The presence of vascularity (96%), irregular margin (94%), and short-to-long axis ratio ≥ 1 (94%) had higher accuracy rates for diagnosis of malignancy.

CONCLUSION: The malignancy rate was 8.8% in our study. Besides internal morphological features, other sonographic features should be considered in the evaluation of complex cystic breast lesions. Due to substantial risk of malignancy and the overlapping sonographic features of benign and malignant lesions, tissue sampling of all complex cysts should be performed.}, } @article {pmid34825640, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Rashid, K and Chaudhary, FA}, title = {The Role of Rehabilitation Exercises on Weight, Functional Strength, and Exercise Adherence in Knee Osteoarthritis Patients.}, journal = {Current rheumatology reviews}, volume = {17}, number = {4}, pages = {397-403}, doi = {10.2174/1573397117666210719101551}, pmid = {34825640}, issn = {1875-6360}, mesh = {*Exercise Therapy ; Humans ; Muscle Strength ; Obesity ; *Osteoarthritis, Knee/therapy ; Overweight ; Treatment Adherence and Compliance ; Treatment Outcome ; }, abstract = {INTRODUCTION: Knee osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of this study was to determine the role of rehabilitation exercises (REs) of lower limbs on weight, functional strength, and exercise adherence in overweight and obese knee OA patients.

MATERIALS AND METHODS: The patients were recruited from the urban community of Lahore, Pakistan. The patients were divided into the rehabilitation group (RG) and control group (CG). The patients in the RG performed the REs of lower limbs and followed the instructions of daily care (IDC), while the patients in the CG only followed the IDC for a 12 weeks period. Outcome measures were assessed at pre-test before grouping and post-test after 12-weeks of interventions. The measures included: weight, functional strength, and exercise adherence. The Paired Samples t-test (for normally distributed data) and the Wilcoxon Signed Ranked Test (for data that was not normally distributed) were used to analyze the differences within groups from pre to post-test measurements. The variance 2 × 2 factors and the Mann Whitney U-test were used to analyze the difference in weight and functional strength between the groups.

RESULTS: The patients in the RG reported a statistically significant weight reduction (p < 0.001) and improvement in the functional strength (p < 0.001) within a group. Similarly, the patients in the CG also reported a significant improvement in the scores of functional strength (p = 0.004) within a group. The improvement in the scores of functional strength was higher in the patients of RG than the CG (p < 0.001). Similarly, the patients in the RG reported a statistically significant reduction in weight than the CG (p < 0.001).

CONCLUSION: The REs could improve weight, functional strength and exercise adherence.}, } @article {pmid34824843, year = {2022}, author = {Eto, R and Nakamura, R and Yamamoto, N and Miyaki, T and Hayama, S and Sonoda, I and Itami, M and Tsujimura, H and Hashimoto, H and Otsuka, M}, title = {Synchronous early-stage breast cancer and axillary follicular lymphoma diagnosed by core needle biopsy: A case report.}, journal = {Molecular and clinical oncology}, volume = {16}, number = {1}, pages = {3}, pmid = {34824843}, issn = {2049-9469}, abstract = {Synchronous double cancers are an infrequent finding. The focus of this study was a case of diagnosed synchronous double breast cancer (BC) and axillary (Ax) follicular lymphoma (FL). The patient was a 73-year-old woman who had been visiting her local doctor for follow-up of a fibroadenoma of the left breast, and was referred to our hospital after being diagnosed with invasive ductal carcinoma (IDC) of the left breast. Ultrasonography (US) revealed enlarged Ax lymph nodes (LNs) and US-guided core needle biopsy (CNB) was performed. CNB revealed no metastasis of IDC; however, a diagnosis of FL was made. Therefore, the patient was diagnosed with synchronous double BC and Ax FL and underwent partial surgical resection of the BC and close monitoring of the FL. To the best of our knowledge, this is the first case of malignant lymphoma diagnosed by CNB of Ax LNs during preoperative BC screening. CNB allows for a shorter waiting time for the examination, and it is considered to be minimally invasive, cost-effective and non-inferior to surgical resection in terms of specimen volume. Therefore, active preoperative evaluation of Ax LNs using US-guided CNB may contribute to BC staging, and may also help diagnose synchronous cancers.}, } @article {pmid34824605, year = {2021}, author = {Gnanamuttupulle, M and Henke, O and Ntundu, SH and Serventi, F and Mwakipunda, LE and Amsi, P and Mremi, A and Chilonga, K and Msuya, D and Chugulu, SG}, title = {Clinicopathological characteristics of breast cancer patients from Northern Tanzania: common aspects of late stage presentation and triple negative breast cancer.}, journal = {Ecancermedicalscience}, volume = {15}, number = {}, pages = {1282}, pmid = {34824605}, issn = {1754-6605}, abstract = {PURPOSE: Breast cancer (BC) is the second most common cancer among Tanzanian women. Oestrogen (ER), progesterone and human epidermal growth factor receptor 2 play major roles in prognosis and treatment but data for Tanzania are sparse. This study aimed to determine these patterns and histological types, tumour grading and staging of BC patients in northern Tanzania for a better understanding of BC in the Sub-Saharan African (SSA) setting.

METHODS: A cross-sectional study recorded newly diagnosed BC cases at Kilimanjaro Christian Medical Centre between October 2018 and March 2019. Receptor status, histological types and grade, clinical stage and socio-demographic were recorded and descriptive and bivariate analyses performed.

RESULTS: 116 patients were enrolled. Median age was 53 years, 71.6% were ≥45 years. The commonest molecular subtype was triple negative breast cancer (TNBC) (n = 33; 28.4%). One hundred and two (87.9%) patients had invasive ductal carcinoma (IDC), poorly differentiated tumours (60; 51.7%) and clinical stage III disease (62; 53.0%). ER negative tumours were associated with poorly differentiated histological grade (relative risk (RR): 1.34 (0.87-2.07)), tumour size > 5 cm (RR: 1.67 (0.33-8.35)) and IDC (RR: 3.35 (0.56-20.23)). Clinical stages III & IV (odds ratio (OR): 1.64 (0.63-4.24)) were associated with hormone receptor (HR) negative tumours and metastasis (OR: 1.60 (0.68-3.74)) with TNBC. 18% of the patients reported about first-degree relatives with BC.

CONCLUSIONS: Most patients presented in advanced stages and TNBC in their menopause. HR negative tumours were associated with poor histological differentiation and IDC. The high percentage of positive family history of BC and the differences in receptor patterns compared to other parts of the world should urge further genetic research on BC in SSA.}, } @article {pmid34824281, year = {2021}, author = {Della Torre, S and Benedusi, V and Pepe, G and Meda, C and Rizzi, N and Uhlenhaut, NH and Maggi, A}, title = {Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6883}, pmid = {34824281}, issn = {2041-1723}, mesh = {Amino Acids, Branched-Chain/pharmacology/therapeutic use ; Amino Acids, Essential/*pharmacology/therapeutic use ; Animals ; Diet Therapy ; Estrogen Receptor alpha/deficiency/*metabolism ; Female ; Lipid Metabolism/drug effects ; Liver/*drug effects/metabolism ; Male ; Mice ; Mice, Knockout ; Ovariectomy/*adverse effects ; Sex Characteristics ; Transcriptome/drug effects ; Weight Gain/drug effects ; }, abstract = {In female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.}, } @article {pmid34820122, year = {2021}, author = {Salih, AM and Hammood, ZD and Kakamad, FH and Othman, S and Ali, RK and Latif, S}, title = {Paget's disease of the breast in male with underlying invasive ductal carcinoma: A case report with review of literature.}, journal = {Annals of medicine and surgery (2012)}, volume = {72}, number = {}, pages = {103035}, pmid = {34820122}, issn = {2049-0801}, abstract = {INTRODUCTION: Paget's disease of the breast is a rare cutaneous eczema-like condition that occurs in the nipple-areolar complex of the breast. The current study aims to report a rare case of Paget's disease of the breast associated with invasive ductal carcinoma in a male breast.

CASE REPORT: A 54-year-old male presented with ulceration of the left nipple-areolar complex that has been progressing over the last 6 months. On examination; there was a palpable axillary lymph node. On ultrasound, a small hypoechoic heterogenous mass was seen beneath the areola (8*4 mm) with surrounding vascularity, and a few axillary lymph nodes with normal morphology and cortical thickness. The mammography revealed some points of calcification arranged in clusters. The patient underwent left side mastectomy and sentinel lymph node biopsy. The result of histopathological examination showed left side unifocal invasive ductal carcinoma.

DISCUSSION: There are two main theories that explain the histogenesis of Paget's disease of the breast with and without underlying malignancy: epidermotropic theory, which suggests an epidermal infiltration of the nipple with Paget cells, and transformative theory, which proposes a malignant transformation of normal glandular cells of the epidermis.

CONCLUSION: The clinical presentation of Paget's disease of the breast is characteristic and should always warn the surgeon of the possibility of underlying malignancy.}, } @article {pmid34816360, year = {2022}, author = {Mizukoshi, K and Fujii, M and Yamauchi, Y and Fukuda, A and Seno, H}, title = {A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.}, journal = {Clinical journal of gastroenterology}, volume = {15}, number = {1}, pages = {199-204}, pmid = {34816360}, issn = {1865-7265}, mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal/surgery ; Constriction, Pathologic/etiology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Retroperitoneal Neoplasms/surgery ; }, abstract = {A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.}, } @article {pmid34812516, year = {2022}, author = {Verbrugge, SAJ and Alhusen, JA and Kempin, S and Pillon, NJ and Rozman, J and Wackerhage, H and Kleinert, M}, title = {Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.}, journal = {Journal of cellular biochemistry}, volume = {123}, number = {2}, pages = {202-214}, doi = {10.1002/jcb.30179}, pmid = {34812516}, issn = {1097-4644}, mesh = {Animals ; *Blood Glucose/genetics/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Humans ; Insulin Resistance/*genetics ; Muscle, Skeletal/*metabolism ; Physical Endurance/*genetics ; *Resistance Training ; }, abstract = {Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.}, } @article {pmid34812466, year = {2021}, author = {Feresin, RG and Johnson, SA and Elam, ML and Pourafshar, S and Navaei, N and Akhavan, NS and Tenenbaum, G and Figueroa, A and Arjmandi, BH}, title = {Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.}, journal = {Food & function}, volume = {12}, number = {24}, pages = {12526-12534}, doi = {10.1039/d1fo01555a}, pmid = {34812466}, issn = {2042-650X}, mesh = {Aged ; Biomarkers/blood ; Bone Density/*drug effects ; Bone Resorption/blood/drug therapy ; Female ; *Fragaria ; Humans ; Hypertension/blood/complications/*drug therapy ; Middle Aged ; Osteoporosis, Postmenopausal/blood/complications/*prevention & control ; Plant Extracts/blood/*pharmacology ; Polyphenols/blood/*pharmacology ; Postmenopause ; }, abstract = {Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m[-2]; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.}, } @article {pmid34805589, year = {2021}, author = {Lee, AY and Pant, A and Pojchanun, K and Lee, CP and An, J and Hashimoto, M and Tan, UX and Leo, CH and Wong, G and Chua, CK and Zhang, Y}, title = {Three-Dimensional Printing of Food Foams Stabilized by Hydrocolloids for Hydration in Dysphagia.}, journal = {International journal of bioprinting}, volume = {7}, number = {4}, pages = {393}, pmid = {34805589}, issn = {2424-8002}, abstract = {Three-dimensional food printing offers the possibility of modifying the structural design, nutrition, and texture of food, which may be used for consumers with special dietary requirements such as dysphagic patients. One of the food matrices that can be used for liquid delivery to dysphagic patients is food foams. Foams are widely used in different food products to adjust food density, rheological properties, and texture. Foams allow the food to stay in the mouth for sufficient time to provide hydration while minimizing the danger of choking. Our work studies the foam properties and printability of both egg white foams and eggless foams with a strong focus on their foaming properties, rheological properties, printability, and suitability for dysphagic patients. Food hydrocolloid, xanthan gum (XG), is added to improve foam stability and rheological properties so that the inks are printable. Rheological and syneresis properties of the pre-printed foam inks are examined. The texture profile and microstructure properties are studied post-printing. International dysphagia diet standardization initiative tests are carried out to assess the inks' potential for dysphagic diets. Inks with XG performed better with minimal water seepage, better foam stability, and excellent printability. This suggests that hydrocolloids lead to more stable food foams that are suitable for 3DFP and safe for hydration delivery to dysphagic patients.}, } @article {pmid34802330, year = {2023}, author = {Fernández, S and Saguy, T and Gaviria, E and Agudo, R and Halperin, E}, title = {The Role of Witnesses in Humiliation: Why Does the Presence of an Audience Facilitate Humiliation Among Victims of Devaluation?.}, journal = {Personality & social psychology bulletin}, volume = {49}, number = {1}, pages = {32-47}, doi = {10.1177/01461672211053078}, pmid = {34802330}, issn = {1552-7433}, mesh = {Humans ; *Shame ; *Anger ; Hostility ; }, abstract = {We examined the role that witnesses play in triggering humiliation. We hypothesized that witnesses trigger humiliation because they intensify the two core appraisals underlying humiliation: unfairness and internalization of a devaluation of the self. However, we further propose that witnesses are not a defining characteristic of humiliating situations. Results of a preliminary study using an event-recall method confirmed that witnesses were as characteristic of humiliating episodes as of those that elicited shame or anger. In Experiments 1 and 2, we manipulated the presence (vs. absence) of witnesses when a professor devalued participants and the hostile tone of this devaluation. As hypothesized, in both experiments, witnesses indirectly increased humiliation via the appraisal of unfairness. Results of Experiment 2 revealed that the presence of witnesses also interacted with hostility, enhancing humiliation. As expected, this moderating effect occurred via the other key appraisal of humiliation (i.e., internalization).}, } @article {pmid34801929, year = {2022}, author = {Mampel, A and Sottile, ML and Denita-Juárez, SP and Vargas, AL and Vargas-Roig, LM}, title = {Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.}, journal = {Cancer genetics}, volume = {260-261}, number = {}, pages = {14-17}, doi = {10.1016/j.cancergen.2021.11.003}, pmid = {34801929}, issn = {2210-7762}, mesh = {Adult ; Aged ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; Humans ; Male ; Neoplasms, Second Primary/*genetics ; Pedigree ; *Point Mutation ; Sequence Analysis, DNA ; *Sequence Deletion ; }, abstract = {Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.}, } @article {pmid34797318, year = {2021}, author = {Chi, MS and Ko, HL and Chen, CC and Hsu, CH and Chen, LK and Cheng, FT}, title = {Single institute experience of intraoperative radiation therapy in early-stage breast cancer.}, journal = {Medicine}, volume = {100}, number = {46}, pages = {e27842}, pmid = {34797318}, issn = {1536-5964}, mesh = {Aged ; Aged, 80 and over ; *Brachytherapy ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local ; Treatment Outcome ; }, abstract = {Intraoperative radiation therapy (IORT) is an alternative to whole breast irradiation in selected early-stage breast cancer patients. In this single institute analysis, we report the preliminary results of IORT given by Axxent Electronic Brachytherapy (eBT) system.Patients treated with lumpectomy and eBT within a minimum follow-up period of 12 months were analyzed. Eligible criteria include being over the age of 45, having unifocal invasive ductal carcinoma (IDC) or ductal carcinoma in situ <3 cm in diameter, not exhibiting lymph node involvement on preoperative images, and negative sentinel lymph node biopsy. The eBT was given by preloaded radiation plans to deliver a single fraction of 20 Gray (Gy) right after lumpectomy.From January 2016 to April 2019, a total of 103 patients were collected. There were 78 patients with IDC and 25 with ductal carcinoma in situ. At a mean follow-up time of 31.1 months (range, 14.5-54.0 months), the local control rate was 98.1%. Two IDC patients had tumor recurrences (1 local and 1 regional failure). Post-IORT radiotherapy was given to 4 patients. There were no cancer related deaths, no distant metastases, and treatment side effects greater than grade 3 documented.We report the largest single institute analysis using the eBT system in Taiwan. The low recurrence and complication rates at a 31.1 month follow-up time support the use of the eBT system in selected early-stage breast cancer patients.}, } @article {pmid34790794, year = {2021}, author = {Zhang, J and Ling, Y and Wang, T and Yan, C and Huang, M and Fan, Z and Ling, R and , }, title = {Analysis of sentinel lymph node biopsy and non-sentinel lymph node metastasis in invasive ductal and invasive lobular breast cancer: a nationwide cross-sectional study (CSBrS-001).}, journal = {Annals of translational medicine}, volume = {9}, number = {20}, pages = {1588}, pmid = {34790794}, issn = {2305-5839}, abstract = {BACKGROUND: Information regarding the implementation of sentinel lymph node biopsy (SLNB) in invasive lobular carcinoma (ILC) is scarce, and whether ILC patients with 1-2 positive sentinel lymph nodes (SLNs) can be omitted from axillary lymph node dissection (ALND) remains controversial. This study aimed to compare involvement of SLNs and non-SLNs between patients with invasive ductal carcinoma (IDC) and ILC.

METHODS: We retrospectively collected the clinical and pathological data of invasive breast cancer patients from 37 medical centers in China from January 2018 to December 2018. The number of resected SLNs, positive rate of SLNs, and non-SLNs metastasis were compared between patients with IDC and ILC.

RESULTS: A total of 6,922 patients were included, comprising 6,650 with IDC (96.1%) and 272 with ILC (3.9%). No difference was observed in the number of resected SLNs between patients with IDC and ILC (IDC: 4.0±1.9 vs. ILC: 3.9±1.6, P=0.352). The positive rate of SLNs was significantly higher in patients with IDC than that in patients with ILC (19.3% in IDC vs. 12.9% in ILC, P=0.008). The difference in positive rate of SLNs between IDC and ILC was mainly attributed to macro-metastasis. For patients with positive SLNs who received ALND, and those with 1-2 positive SLNs, the metastatic rate of non-SLNs in the ILC group was higher than that in the IDC group (for patients with positive SLNs: 50.0% in ILC vs. 39.9% in IDC, P=0.317; for patients with 1-2 positive SLNs: 45.4% in ILC vs. 34.8% in IDC, P=0.366), but the differences were not statistically significant.

CONCLUSIONS: Patients with ILC had similar number of resected SLNs and lower positive rate of SLNs compared to those with IDC. In participants with 1-2 positive SLNs, the ILC group had an increased tendency for non-SLNs metastasis compared with the IDC group. Surgeons may need to be more cautious about omitting ALND for ILC patients with 1-2 positive SLNs.}, } @article {pmid34788615, year = {2021}, author = {Sebag, SC and Zhang, Z and Qian, Q and Li, M and Zhu, Z and Harata, M and Li, W and Zingman, LV and Liu, L and Lira, VA and Potthoff, MJ and Bartelt, A and Yang, L}, title = {ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.}, journal = {Cell reports}, volume = {37}, number = {7}, pages = {110003}, pmid = {34788615}, issn = {2211-1247}, support = {P30 DK054759/DK/NIDDK NIH HHS/United States ; R01 DK108835/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue, Brown/*metabolism ; Alcohol Dehydrogenase/*metabolism/physiology ; Animals ; Diet ; HEK293 Cells ; Homeostasis/physiology ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Nitric Oxide/chemistry/*metabolism ; Obesity/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Thermogenesis/physiology ; Uncoupling Protein 1/metabolism/physiology ; }, abstract = {Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.}, } @article {pmid34781971, year = {2021}, author = {Kostoglou, A and Vlastos, D and Bakalis, A and Ghosh, D}, title = {Breast cancer-associated opsoclonus-myoclonus syndrome: a case report.}, journal = {World journal of surgical oncology}, volume = {19}, number = {1}, pages = {328}, pmid = {34781971}, issn = {1477-7819}, mesh = {Adult ; *Breast Neoplasms/complications ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Opsoclonus-Myoclonus Syndrome/etiology ; Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {BACKGROUND: Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.

CASE PRESENTATION: A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.

CONCLUSIONS: In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.}, } @article {pmid34781210, year = {2021}, author = {Jeong, JS and Cho, KJ and Kim, D and Lee, YS and Song, JS}, title = {Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.}, journal = {Pathology, research and practice}, volume = {228}, number = {}, pages = {153678}, doi = {10.1016/j.prp.2021.153678}, pmid = {34781210}, issn = {1618-0631}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Middle Aged ; Salivary Ducts/pathology ; Salivary Gland Neoplasms/genetics/*pathology ; }, abstract = {AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.

METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.

CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.}, } @article {pmid34778983, year = {2022}, author = {O'Donnell, AJ and Greischar, MA and Reece, SE}, title = {Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.}, journal = {Parasite immunology}, volume = {44}, number = {3}, pages = {e12898}, pmid = {34778983}, issn = {1365-3024}, support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Circadian Rhythm/physiology ; Fasting ; *Malaria/parasitology/prevention & control ; *Parasites ; *Plasmodium chabaudi/physiology ; }, abstract = {AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.

METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process.

RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.}, } @article {pmid34777203, year = {2021}, author = {Gogia, B and Shanina, E and Fang, X and He, J and Li, X}, title = {Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {735895}, pmid = {34777203}, issn = {1664-2295}, abstract = {Background: Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS). Case Description: We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot. There are coexisting long-tract disturbance and lower-extremity weakness. Treatment with diazepam provided symptomatic relief while plasma exchange (PLEX) did not lead to significant clinical improvement. The patient was bedridden within 3 months and passed away within 6 months from symptom onset. Conclusion: This case highlights the importance of recognition of uncommon presentation of SPS and its oncological significance. This entity requires a high degree of suspicion for initiation of the proper workup. The rapid identification and treatment of the underlying tumor might offer the best chance for recovery.}, } @article {pmid34771617, year = {2021}, author = {Tzelepi, V and Grypari, IM and Logotheti, S and Kontogiannis, S and Kallidonis, P and Melachrinou, M and Zolota, V}, title = {Contemporary Grading of Prostate Cancer: The Impact of Grading Criteria and the Significance of the Amount of Intraductal Carcinoma.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771617}, issn = {2072-6694}, support = {56570000//University of Patras/ ; }, abstract = {(1) Background: Prognostic grade group (PGG) is an important prognostic parameter in prostate cancer that guides therapeutic decisions. The cribriform pattern and intraductal carcinoma (IDC) are two histological patterns, that have additional prognostic significance. However, discrepancies exist regarding the handling of IDC according to the guidelines published by two international genitourinary pathology societies. Furthermore, whether, in addition to its presence, the amount of IDC is also of importance has not been studied before. Lastly, the handling of tertiary patterns has also been a matter of debate in the literature. (2) Methods: A total of 129 prostatectomy cases were retrieved and a detailed histopathologic analysis was performed. (3) Results: Two cases (1.6%) upgraded their PGG, when IDC was incorporated in the grading system. The presence and the amount of IDC, as well as the presence of cribriform carcinoma were associated with adverse pathologic characteristics. Interestingly, in six cases (4.7%) there was a difference in PGG when using the different guidelines regarding the handling of tertiary patterns. In total, 6.2% of the cases would be assigned a different grade depending on the guidelines followed. (4) Conclusions: These findings highlight a potential area of confusion among pathologists and clinicians and underscore the need for a consensus grading system.}, } @article {pmid34771530, year = {2021}, author = {Kanavati, F and Tsuneki, M}, title = {Breast Invasive Ductal Carcinoma Classification on Whole Slide Images with Weakly-Supervised and Transfer Learning.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771530}, issn = {2072-6694}, abstract = {Invasive ductal carcinoma (IDC) is the most common form of breast cancer. For the non-operative diagnosis of breast carcinoma, core needle biopsy has been widely used in recent years for the evaluation of histopathological features, as it can provide a definitive diagnosis between IDC and benign lesion (e.g., fibroadenoma), and it is cost effective. Due to its widespread use, it could potentially benefit from the use of AI-based tools to aid pathologists in their pathological diagnosis workflows. In this paper, we trained invasive ductal carcinoma (IDC) whole slide image (WSI) classification models using transfer learning and weakly-supervised learning. We evaluated the models on a core needle biopsy (n = 522) test set as well as three surgical test sets (n = 1129) obtaining ROC AUCs in the range of 0.95-0.98. The promising results demonstrate the potential of applying such models as diagnostic aid tools for pathologists in clinical practice.}, } @article {pmid34769077, year = {2021}, author = {Kohlhase, DR and McCabe, CE and Singh, AK and O'Rourke, JA and Graham, MA}, title = {Comparing Early Transcriptomic Responses of 18 Soybean (Glycine max) Genotypes to Iron Stress.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769077}, issn = {1422-0067}, support = {3625-21220-006-00D//USDA-ARS/ ; IOW04714//USDA/ ; FAR0024859//North Central Soybean Research Program/ ; }, mesh = {*Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Iron/*metabolism ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; Transcriptome ; }, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress that negatively affects soybean (Glycine max [L.] Merr.) production. Much of our knowledge of IDC stress responses is derived from model plant species. Gene expression, quantitative trait loci (QTL) mapping, and genome-wide association studies (GWAS) performed in soybean suggest that stress response differences exist between model and crop species. Our current understanding of the molecular response to IDC in soybeans is largely derived from gene expression studies using near-isogenic lines differing in iron efficiency. To improve iron efficiency in soybeans and other crops, we need to expand gene expression studies to include the diversity present in germplasm collections. Therefore, we collected 216 purified RNA samples (18 genotypes, two tissue types [leaves and roots], two iron treatments [sufficient and deficient], three replicates) and used RNA sequencing to examine the expression differences of 18 diverse soybean genotypes in response to iron deficiency. We found a rapid response to iron deficiency across genotypes, most responding within 60 min of stress. There was little evidence of an overlap of specific differentially expressed genes, and comparisons of gene ontology terms and transcription factor families suggest the utilization of different pathways in the stress response. These initial findings suggest an untapped genetic potential within the soybean germplasm collection that could be used for the continued improvement of iron efficiency in soybean.}, } @article {pmid34765304, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study.}, journal = {American journal of cancer research}, volume = {11}, number = {10}, pages = {4966-4980}, pmid = {34765304}, issn = {2156-6976}, abstract = {To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.}, } @article {pmid34764233, year = {2021}, author = {Saleem, T and Mi, K and Pathak, R and Yari, K and Lu, K}, title = {Concurrent Breast Carcinoma and Follicular Lymphoma: A Case Series.}, journal = {The American journal of case reports}, volume = {22}, number = {}, pages = {e931772}, pmid = {34764233}, issn = {1941-5923}, mesh = {Axilla ; *Breast Neoplasms/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Lymphoma, Follicular/diagnosis ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND The incidence of multiple primaries in cancer patients is 2-17%. However, the synchronous co-occurrence of adenocarcinoma of the breast and follicular lymphoma is rare. CASE REPORT We describe a case series of 3 post-menopausal women who presented to our institute with a breast lump. On further investigations, 2 of them had invasive ductal carcinoma and 1 had invasive lobular carcinoma of the breast. All 3 cancers were estrogen/progesterone receptor (ER/PR)-positive and human epidermal growth factor receptor 2 (HER-2)-negative. During the staging PET scans, all 3 patients had increased FDG uptake in axillary, mesenteric, and inguinal lymph nodes, respectively, raising concerns for metastatic disease. However, subsequent biopsies revealed them as follicular lymphomas occurring as a second concurrent primary malignancy. All patients underwent radical mastectomies with sentinel lymph node dissection followed by chemotherapy and hormonal therapy. Most of the lymphomas were low grade, which the oncologist closely followed. CONCLUSIONS Very few cases of breast cancer and follicular lymphoma co-occur; this is not limited to the axillary lymph nodes and can occur in any part of the lymphatic chain. Regional lymph node enlargement detected on examination or imaging does not always indicate metastasis. A high index of suspicion is needed followed by lymph node biopsy to rule out any second primary malignancy.}, } @article {pmid34763167, year = {2021}, author = {Mallapasi, MN and Kusumanegara, J and Kabo, P and Usman, U and Mulyono, MT and Faruk, M}, title = {Cardiac metastasis of triple-negative breast cancer mimicking myxoma: A case report.}, journal = {International journal of surgery case reports}, volume = {88}, number = {}, pages = {106552}, pmid = {34763167}, issn = {2210-2612}, abstract = {INTRODUCTION: Metastatic heart tumors are rare, occurring in 1.5-20% of cancer patient autopsies. Lymphoma, melanoma, leukemia, and carcinomas of the lung, esophagus, and breast are the most prevalent causes of these metastases, although they can originate from any malignant tumor. Here we report a case of triple-negative breast cancer with cardiac metastasis mimicking myxoma.

PRESENTATION OF CASE: A 39-year-old woman presented at the emergency department with shortness of breath. Vital signs were hypotension and tachypnea. There were coarse crackles at the bases of both lungs. Electrocardiography results showed a normal sinus rhythm. Chest X-ray revealed cardiomegaly with signs of pulmonary edema. Echocardiography revealed a large left atrial (LA) mass protruding to the mitral valve and attached to the interatrial septum during diastole. The patient was diagnosed with cardiogenic shock, acute kidney injury, elevated liver enzymes, and an LA mass. Surgical excision through median sternotomy was planned. Intraoperatively, an LA mass was found. The histopathology evaluation showed an LA mass with invasive ductal carcinoma of metastatic breast tumors. Immunohistochemistry (IHC) confirmed the diagnosis of triple-negative breast cancer that had metastasized to the heart. Postoperative echocardiography confirmed complete excision of the tumor.

DISCUSSION: Breast cancer that has metastasized to the heart is uncommon. This patient was referred to the surgical oncology section for the treatment of triple-negative breast cancer with cardiac metastasis.

CONCLUSION: A heart mass should be suspected of having metastasized if the patient has a history of malignancy, even if it occurred several years earlier.}, } @article {pmid34761609, year = {2021}, author = {Chen, S and Wang, J and Yang, L and Ji, M and Chen, S}, title = {Comparative analysis of clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast and invasive ductal carcinoma: results from SEER database.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {26}, number = {5}, pages = {1991-2002}, pmid = {34761609}, issn = {2241-6293}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/*classification/mortality/*pathology ; Carcinoma, Ductal, Breast/*classification/mortality/*pathology ; Carcinoma, Papillary/*classification/mortality/*pathology ; Databases, Factual ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; SEER Program ; Survival Rate ; Young Adult ; }, abstract = {PURPOSE: To investigate the difference of clinicopathologic characteristics and prognosis between invasive papillary carcinoma (IPC) and invasive ductal carcinoma (IDC) in breast cancer patients, and to further confirm the influence of molecular subtype on prognosis of IPC.

METHODS: A total of 158,132 eligible patients from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, of which 348 patients were IPC and 157,784 patients were IDC. We assessed the clinicopathologic characteristics, molecular subtypes and prognostic value of IPC and compared them with those of IDC.

RESULTS: IPC was more frequently presented with older age at diagnosis, less proportion of married and white race, lower grade, smaller tumor size, higher rates of negative nodal status, more AJCC stage I disease and HR+/Her2- breast cancer, and was less likely to be treated with mastectomy, chemotherapy, and radiation therapy than IDC (p<0.05). IPC had a better 5-year breast cancer-specific survival (BCSS) and overall survival (OS) rates than IDC. After adjusting confounding and matching the confounding factors, IPC patients were still associated with better BCSS. Regarding patients with specific subtypes, patients with IPC had more HR+/Her2- subtypes. In addition, HR+/Her2--IPC patients had a better BCSS than HR+/Her2--IDC patients, but OS was similar between the two groups. However, BCSS and OS did not differ in the two groups after matching the confounding factors. Subgroup analysis indicated that molecular subtype may be the main confounding factor in IPC prognosis.

CONCLUSIONS: IPC showed more favorable behavior than IDC, but prognosis was not as favorable as people once thought. The determination of the appropriate therapeutic regimen for IPC still needs to be made according to risk factors such as histological grade, pathological stage and molecular subtype.}, } @article {pmid34760317, year = {2021}, author = {Cozzi, S and Najafi, M and Bardoscia, L and Ruggieri, MP and Giaccherini, L and Blandino, G and Botti, A and Ciammella, P and Iotti, C}, title = {Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {26}, number = {5}, pages = {827-832}, pmid = {34760317}, issn = {1507-1367}, abstract = {BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy.

CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient.

DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient's specifications.

CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival.}, } @article {pmid34756596, year = {2022}, author = {Barrault-Couchouron, M and Béracochéa, M and Dorval, M and Allafort, V and Barthélémy, V and Garguil, V and Auriacombe, M and Bussières, E and M'bailara, K}, title = {[Tobacco and alcohol consumption in women treated for breast cancer in a department of surgical oncology: Frequent behaviours to consider].}, journal = {Bulletin du cancer}, volume = {109}, number = {3}, pages = {307-317}, doi = {10.1016/j.bulcan.2021.07.005}, pmid = {34756596}, issn = {1769-6917}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking/*epidemiology ; Breast Neoplasms/*psychology/*surgery ; Cross-Sectional Studies ; Female ; Health Behavior ; Humans ; Middle Aged ; Prevalence ; Self Report ; Surgery Department, Hospital ; Surgical Oncology ; Tobacco Use/*epidemiology ; }, abstract = {INTRODUCTION: Tobacco and alcohol represent the two most important risk factors increasing cancer incidence and mortality, particularly among women with breast cancer. However, few researches have focused on the consumption of psychoactive substances in women treated for breast cancer. The present study describes the prevalence of tobacco and alcohol consumption and their relationships with the sociodemographic, medical and psychological variables in a population of women receiving surgery treatment for breast cancer.

METHODS: Between October 2014 and August 2015, a group of women receiving breast cancer treatment were recruited to participate to a screening and brief intervention program (SBI) for the consumption of tobacco and alcohol, adapted to the oncology context. Data on tobacco and alcohol consumption were collected using two questionnaires : the smoking status identification (NIDA) and alcohol consumption (AUDIT-C). A questionnaire for socio- demographic data and two for psychological data (Thermometer of psychological distress; ESAS), have been used. The medical data were reported by participants and verified on medical records.

RESULTS: In a total of 11 months, 120 women with breast cancer were included in this study. A large majority of patients were hospitalized for a first-time cancer (80.8%), type invasive ductal carcinoma (70.8%) and were receiving surgery as primary treatment (45%). Furthermore, 30.8% of the women reported tobacco consumption and 38.4% high-risk alcohol consumption. Regarding mental health, 40.8% presented moderate to intense levels of psychological distress. No significant relationships were found between consumption scores and sociodemographic, medical or psychological characteristics. Only the patient's age was negatively associated with tobacco consumption.

DISCUSSION: Tobacco and at-risk alcohol consumption are frequently reported behaviors during breast cancer treatment. Intervention strategies targeting risk behaviors related to addictive consumption should be implemented during the full treatment of breast cancer patients.}, } @article {pmid34754678, year = {2021}, author = {Barron, M and Asaad, A and Idaewor, P and Rasheed, N and Saad Abdalla Al-Zawi, A}, title = {Breast Apocrine Carcinoma Detected Incidentally as Axillary Lymphadenopathy in a CT Scan.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e18523}, pmid = {34754678}, issn = {2168-8184}, abstract = {Breast apocrine cell pathology varieties include benign papilloma, non-high-grade apocrine ductal carcinoma in situ (DCIS), and breast invasive apocrine carcinoma (BAC). BAC is a rare type of invasive breast cancer and is histologically distinguished by large-sized cells with copious eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. Its prognosis is similar to breast invasive ductal carcinoma, of no special type (IDC-NST), when matched for tumour stage and histological grade. In this paper, we report the case of a 75-year-old lady presenting with apocrine carcinoma of the left breast diagnosed at the stage of mediastinal lymph node metastasis.}, } @article {pmid34753585, year = {2021}, author = {Othong, J and Boonmak, J and Cheansirisomboon, A and Puangmali, T and Phanchai, W and Youngme, S}, title = {pH modulated luminescent switching and discriminative detection of amino acid based on metal-organic framework.}, journal = {Analytica chimica acta}, volume = {1187}, number = {}, pages = {339157}, doi = {10.1016/j.aca.2021.339157}, pmid = {34753585}, issn = {1873-4324}, mesh = {Amino Acids ; Humans ; Hydrogen-Ion Concentration ; Luminescence ; *Metal-Organic Frameworks ; Reproducibility of Results ; }, abstract = {The detection of glutamic (Glu) or aspartic (Asp) acids is vital for human nutrition and diagnosis of disease. Herein, the dht ligand containing hydroxy group (-OH) is used to design and synthesize a 2D luminescent [Cd2(idc)(dht)(H2O)4] (1); H2idc = 4,5-imidazoledicarboxylic acid and H2dht = 2,5-dihydroxyterephthalic acid for sensing amino acids. The compound 1 can discriminatively detect Asp and Glu among other amino acids through blue-shifted emission (yellow → green). The dual sensing mechanism may be attributed to the intermolecular excited-state proton transfer between MOF and water to produce keto form along with the subsequent switching of keto form to enol form by protonation causing the increased band gap energy. This material can serve several benefits in terms of high selectivity, fast response (30s), good reproducibility and low LOD value of 11.34 μM which is less than the harmful concentration of Glu for human health (>400 μM). In addition, 1 shows the broad range detection of Glu covering in safe and unsafe levels. For on-site detection of Glu, MOF-based paper is devised and can be applied through color-scanning application in smartphone. Besides, this sensor can serve to detect Glu in real samples with good recovery.}, } @article {pmid34745804, year = {2021}, author = {Maglic, D and Moss, W and Pires, G and Agarwal, A and Matsen, C and Kwok, A}, title = {A Case Report of Misdiagnosed Breast Implant-associated Anaplastic Large Cell Lymphoma with Lymphatic Extension.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {9}, number = {11}, pages = {e3916}, pmid = {34745804}, issn = {2169-7574}, abstract = {Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare peripheral T-cell lymphoma associated with textured implants and usually presents as a late-onset periprosthetic seroma. We present a 70-year-old woman with a history of left breast invasive ductal carcinoma treated with mastectomy and textured implant-based reconstruction, and subsequent adjuvant chemotherapy due to lymphovascular extension. Eleven years following her reconstruction, the patient developed a periprosthetic seroma. Fine needle aspiration and partial capsulectomy were performed, but appropriate pathologic evaluation was not initially submitted. She then presented with lymphadenopathy, which was biopsied and revealed BIA-ALCL within an axillary lymph node. Despite implant explantation, complete capsulectomy, axillary lymph node dissection, and excision of groin lymphadenopathy, no evidence of primary ALCL was appreciated. This initially misdiagnosed case demonstrates the importance of following the National Comprehensive Cancer Network guidelines when a patient presents with late onset breast periprosthetic effusions.}, } @article {pmid34743937, year = {2021}, author = {Ben-Zvi Feldman, S and Soroker, N and Levy, DA}, title = {Lesion-behaviour mapping reveals multifactorial neurocognitive processes in recognition memory for unfamiliar faces.}, journal = {Neuropsychologia}, volume = {163}, number = {}, pages = {108078}, doi = {10.1016/j.neuropsychologia.2021.108078}, pmid = {34743937}, issn = {1873-3514}, mesh = {Brain Mapping ; *Facial Recognition ; Humans ; Memory ; Mental Recall ; Pattern Recognition, Visual ; *Recognition, Psychology ; }, abstract = {Face recognition abilities, which play a critical role in social interactions, involve face processing and identifying familiar faces, but also remembering one-off encounters with previously unfamiliar faces. Previous functional imaging and lesion studies have found evidence for temporal, frontal, and parietal contributions to episodic recognition memory for previously unfamiliar faces. However, the functional contributions of these regions remain unclear. We, therefore, conducted a systematic group analysis of this memory function using lesion-behavior mapping. 95 first-event stroke patients (53 with right- and 42 with left-hemisphere damage) in the sub-acute phase performed the Wechsler Memory Scale (WMS-III) face recognition memory subtest. We analyzed their performance relative to 75 healthy controls, using signal detection measures. To identify brain lesions specifically implicated in face recognition deficits, we used voxel-based lesion-behavior mapping (VLBM; an analysis comparing the performance of participants with and without damage affecting a given voxel). Behavioral analysis disclosed a pronounced impairment in the performance of patients with right hemisphere damage. Frontal damage was associated with an increased amount of false alarms (i.e., failed rejection of new face items) and overly liberal criterion setting, without affecting the recognition of studied faces. In contrast, parietal damage was associated with impaired recognition of studied faces, which was more pronounced in immediate than in delayed retrieval. These findings suggest the existence of multifactorial neurocognitive processes in recognition memory for unfamiliar faces.}, } @article {pmid34743445, year = {2021}, author = {Plante, A and Dallaire, F and Grosset, AA and Nguyen, T and Birlea, M and Wong, J and Daoust, F and Roy, N and Kougioumoutzakis, A and Azzi, F and Aubertin, K and Kadoury, S and Latour, M and Albadine, R and Prendeville, S and Boutros, P and Fraser, M and Bristow, RG and van der Kwast, T and Orain, M and Brisson, H and Benzerdjeb, N and Hovington, H and Bergeron, A and Fradet, Y and Têtu, B and Saad, F and Trudel, D and Leblond, F}, title = {Dimensional reduction based on peak fitting of Raman micro spectroscopy data improves detection of prostate cancer in tissue specimens.}, journal = {Journal of biomedical optics}, volume = {26}, number = {11}, pages = {}, pmid = {34743445}, issn = {1560-2281}, mesh = {Area Under Curve ; *Carcinoma, Intraductal, Noninfiltrating ; Humans ; Machine Learning ; Male ; *Prostatic Neoplasms/diagnostic imaging ; Spectrum Analysis, Raman ; }, abstract = {SIGNIFICANCE: Prostate cancer is the most common cancer among men. An accurate diagnosis of its severity at detection plays a major role in improving their survival. Recently, machine learning models using biomarkers identified from Raman micro-spectroscopy discriminated intraductal carcinoma of the prostate (IDC-P) from cancer tissue with a ≥85 % detection accuracy and differentiated high-grade prostatic intraepithelial neoplasia (HGPIN) from IDC-P with a ≥97.8 % accuracy.

AIM: To improve the classification performance of machine learning models identifying different types of prostate cancer tissue using a new dimensional reduction technique.

APPROACH: A radial basis function (RBF) kernel support vector machine (SVM) model was trained on Raman spectra of prostate tissue from a 272-patient cohort (Centre hospitalier de l'Université de Montréal, CHUM) and tested on two independent cohorts of 76 patients [University Health Network (UHN)] and 135 patients (Centre hospitalier universitaire de Québec-Université Laval, CHUQc-UL). Two types of engineered features were used. Individual intensity features, i.e., Raman signal intensity measured at particular wavelengths and novel Raman spectra fitted peak features consisting of peak heights and widths.

RESULTS: Combining engineered features improved classification performance for the three aforementioned classification tasks. The improvements for IDC-P/cancer classification for the UHN and CHUQc-UL testing sets in accuracy, sensitivity, specificity, and area under the curve (AUC) are (numbers in parenthesis are associated with the CHUQc-UL testing set): +4  %   (+8  %  ), +7  %   (+9  %  ), +2  %   (6%), +9 (+9) with respect to the current best models. Discrimination between HGPIN and IDC-P was also improved in both testing cohorts: +2.2  %   (+1.7  %  ), +4.5  %   (+3.6  %  ), +0  %   (+0  %  ), +2.3 (+0). While no global improvements were obtained for the normal versus cancer classification task [+0  %   (-2  %  ), +0  %   (-3  %  ), +2  %   (-2  %  ), +4 (+3)], the AUC was improved in both testing sets.

CONCLUSIONS: Combining individual intensity features and novel Raman fitted peak features, improved the classification performance on two independent and multicenter testing sets in comparison to using only individual intensity features.}, } @article {pmid34736165, year = {2021}, author = {Mojra, A and Hooman, K}, title = {Viscoelastic parameters of invasive breast cancer in correlation with porous structure and elemental analysis data.}, journal = {Computer methods and programs in biomedicine}, volume = {212}, number = {}, pages = {106482}, doi = {10.1016/j.cmpb.2021.106482}, pmid = {34736165}, issn = {1872-7565}, mesh = {*Breast Neoplasms/diagnostic imaging ; Elasticity ; Female ; Humans ; Porosity ; Stress, Mechanical ; Viscosity ; }, abstract = {BACKGROUND AND OBJECTIVE: Invasive ductal carcinoma (IDC) is the most common and aggressive type of breast cancer. As many clinical diagnoses are concerned with the tumor behavior at the compression, the IDC characterization using a compression test is performed in the present study. In the field of tissue characterization, most of the previous studies have focused on healthy and cancerous breast tissues at the cellular level; however, characterization of cancerous tissue at the tissue level has been under-represented, which is the target of the present study.

METHODS: Throughout this article, 18 IDC samples are tested using a ramp-relaxation test. The strain rate in the ramp phase is similar for all samples, whereas the strain level is set at 2,4 and 6%. The experimental stress-time data is interpolated by a viscoelastic model. Two relaxation times, as well as the instantaneous and long-term shear moduli, are calculated for each specimen.

RESULTS: The results show that the long-term and instantaneous shear moduli vary in the range of 0.31-17.03 kPa and 6.03-55.13 kPa, respectively. Our assessment of the viscoelastic parameters is accompanied by observing structural images of the IDCs and inspecting their elemental composition. It is concluded that IDCs with lower Magnesium to Calcium ratio (Mg:Ca) have smaller shear modulus and longer relaxation time, with a p-value of 0.001 and 0.01 for the correlation between Mg:Ca and long-term shear modulus, and Mg:Ca and early relaxation time.

CONCLUSIONS: Our identification of the IDC viscoelastic parameters can contribute to the IDC inspection at the tissue level. The results also provide useful information for modeling of breast cancer.}, } @article {pmid34733733, year = {2021}, author = {Deshpande, N and Murti, S and Singh, R and Coker, C and Rudra, S and Paudel, N and Fan, KL and Greenwalt, IT}, title = {Management of invasive ductal carcinoma in hypermobile Ehlers-Danlos syndrome: a case report.}, journal = {Gland surgery}, volume = {10}, number = {9}, pages = {2861-2866}, pmid = {34733733}, issn = {2227-684X}, abstract = {Literature is sparse regarding the management and long-term outcomes of breast cancer in patients with Ehlers-Danlos syndrome (EDS). Of the EDS subtypes, hypermobile Ehlers-Danlos Syndrome (hEDS) is associated with cardiovascular dysautonomia which manifests as spontaneous episodes of tachycardia and hypotension. Given this clinical autonomic system impact, hEDS is known to have significant intraoperative risk and postoperative complications. However, outcomes of hEDS patients have not been specifically studied in the field of breast cancer surgery. Here we present a case of a 62-year-old female with hEDS and node-positive invasive ductal breast carcinoma. Given the patient's medical history of hEDS, close attention was given to the patient's intraoperative vital signs and predisposition for poor wound healing. The patient underwent left Goldilocks mastectomy with left axillary lymph node dissection. Due to cardiac comorbidities, she was not a candidate for neoadjuvant or adjuvant chemotherapy. The patient tolerated adjuvant radiation and endocrine therapy without side effects, and has remained free of local, regional, and distant cancer recurrence following treatment. This case report highlights a literature gap in the surgical and radiation therapy management of breast cancer in patients with hEDS. Although breast surgery and radiation therapy in patients with invasive breast cancer and hEDS can be a safe management option, we discuss how perioperative complications must be cautiously navigated and how treatment must be tailored to individuals' specific hEDS variant to ensure optimal patient safety and positive long-term outcomes.}, } @article {pmid34725819, year = {2022}, author = {Chen, X and Zhang, C and Guo, D and Wang, Y and Hu, J and Hu, J and Wang, S and Liu, X}, title = {Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.}, journal = {European journal of clinical investigation}, volume = {52}, number = {4}, pages = {e13704}, doi = {10.1111/eci.13704}, pmid = {34725819}, issn = {1365-2362}, support = {2017YFC0108602//The National Key Research and Development Program of China/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate ; }, abstract = {OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.

METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.

RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ[2]  = 18784, p < 0.001; χ[2]  = 47.1, p < 0.001; χ[2]  = 20, p < 0.001).

CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.}, } @article {pmid34722229, year = {2021}, author = {Liu, L and Mei, N and Yin, B and Peng, W}, title = {Correlation of DCE-MRI Perfusion Parameters and Molecular Biology of Breast Infiltrating Ductal Carcinoma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {561735}, pmid = {34722229}, issn = {2234-943X}, abstract = {OBJECTIVE: We aimed to investigate the correlation of the perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with the molecular biological expression of breast infiltrating ductal carcinoma (IDC) in order to guide appropriate therapeutic advice and clinical outcome prediction.

MATERIALS AND METHODS: In a prospective analysis of 67 patients with breast IDC, preoperative DCE-MRI and routine MRI images were obtained. The double-chamber model (extended Tofts model) was employed to calculate the perfusion parameters. Postoperative pathological immunohistochemistry was examined, including human epidermal growth factor receptor 2 (HER-2), estrogen receptor (ER), progesterone receptor (PR), cell nuclear-associated antigen (Ki-67), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR). Statistical analysis was applied to explore the relationship between the perfusion parameters and the molecular biomarkers of breast cancer.

RESULTS: A total of 67 lesions were included in our study. The mean maximum diameter of lesions was 4.48 ± 1.73 cm. Perfusion parameters had no correlation with tumor diameters (p > 0.05). The volume transfer constant (K [trans]) and the rate constant (k ep) had positive correlations with Ki-67 (p < 0.05). The plasma volume ratio (v p) had a statistical difference between CK5/6 positivity and CK5/6 negativity. The maximum rising slope (MAX Slope) was higher in HER-2-enriched tumors than that in luminal A or B tumors (p < 0.05). k ep was higher in HER-2-enriched tumors than that in luminal A tumors (p < 0.05). The extravascular extracellular space volume fraction (v e) was higher in triple-negative tumors than that in HER-2-enriched and in luminal A and B tumors (p < 0.05). The time to peak enhancement (TTP) was lower in HER-2-enriched tumors than that in luminal A and B tumors (p < 0.05). Maximum concentration (MAX Conc) was higher in triple-negative tumors than that in luminal B tumors (p < 0.05).

CONCLUSION: DCE-MRI perfusion parameters can behave as a noninvasive tool to assess the molecular biological expression and the molecular subtypes of breast IDC. They may aid in predicting breast IDC invasiveness, metastasis, and prognosis.}, } @article {pmid34718690, year = {2022}, author = {Shimizu, N and Myojin, M and Tamura, M and Nishiyama, N and Yamashiro, K and Yuyama, Y and Okazaki, Y and Suzuki, Y and Takahashi, M}, title = {Significance of boost radiotherapy in early invasive ductal breast cancer with ductal carcinoma in situ component under negative surgical margins.}, journal = {Journal of radiation research}, volume = {63}, number = {1}, pages = {80-87}, pmid = {34718690}, issn = {1349-9157}, mesh = {*Breast Neoplasms/radiotherapy/surgery ; *Carcinoma, Intraductal, Noninfiltrating/pathology/radiotherapy/surgery ; Female ; Humans ; Margins of Excision ; Mastectomy, Segmental/adverse effects ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; }, abstract = {We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.}, } @article {pmid34717732, year = {2021}, author = {Ropri, AS and DeVaux, RS and Eng, J and Chittur, SV and Herschkowitz, JI}, title = {Cis-acting super-enhancer lncRNAs as biomarkers to early-stage breast cancer.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {101}, pmid = {34717732}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line ; Disease Progression ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/*genetics ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: Increased breast cancer screening over the past four decades has led to a substantial rise in the diagnosis of ductal carcinoma in situ (DCIS). Although DCIS lesions precede invasive ductal carcinoma (IDC), they do not always transform into cancer. The current standard-of-care for DCIS is an aggressive course of therapy to prevent invasive and metastatic disease resulting in over-diagnosis and over-treatment. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive disease. Recent studies show that super-enhancers, in addition to promoting other gene transcription, are themselves transcribed producing super-enhancer associated long noncoding RNAs (SE-lncRNAs). These SE-lncRNAs can interact with their associated enhancer regions in cis and influence activities and expression of neighboring genes. Furthermore, they represent a novel, untapped group of therapeutic targets.

METHODS: With an integrative analysis of enhancer loci with global expression of SE-lncRNAs in the MCF10A progression series, we have identified differentially expressed SE-lncRNAs which can identify mechanisms for DCIS to IDC progression. Furthermore, cross-referencing these SE-lncRNAs with patient samples in the The Cancer Genome Atlas (TCGA) database, we have unveiled 27 clinically relevant SE-lncRNAs that potentially interact with their enhancer to regulate nearby gene expression. To complement SE-lncRNA expression studies, we conducted an unbiased global analysis of super-enhancers that are acquired or lost in progression.

RESULTS: Here we designate SE-lncRNAs RP11-379F4.4 and RP11-465B22.8 as potential markers of progression of DCIS to IDC through regulation of the expression of their neighboring genes (RARRES1 and miR-200b, respectively). Moreover, we classified 403 super-enhancer regions in MCF10A normal cells, 627 in AT1, 1053 in DCIS, and 320 in CA1 cells. Comparison analysis of acquired/lost super-enhancer regions with super-enhancer regions classified in 47 ER positive patients, 10 triple negative breast cancer (TNBC) patients, and 11 TNBC cell lines reveal critically acquired pathways including STAT signaling and NF-kB signaling. In contrast, protein folding, and local estrogen production are identified as major pathways lost in progression.

CONCLUSION: Collectively, these analyses identify differentially expressed SE-lncRNAs and acquired/lost super-enhancers in progression of breast cancer important for promoting DCIS lesions to IDC.}, } @article {pmid34716548, year = {2021}, author = {Cattaneo, C and Rieg, S and Schwarzer, G and Müller, MC and Blümel, B and Kern, WV}, title = {Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?.}, journal = {Infection}, volume = {49}, number = {6}, pages = {1289-1297}, pmid = {34716548}, issn = {1439-0973}, mesh = {Adult ; Aged ; *Bacteremia/epidemiology ; *Communicable Diseases ; Enterococcus faecalis ; *Gram-Positive Bacterial Infections/epidemiology ; Humans ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; *Sepsis ; }, abstract = {PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes.

METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression.

RESULTS: A total of 151 patients with a median age of 68 years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76).

CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.}, } @article {pmid34712178, year = {2021}, author = {Levit-Binnun, N and Arbel, K and Dorjee, D}, title = {The Mindfulness Map: A Practical Classification Framework of Mindfulness Practices, Associated Intentions, and Experiential Understandings.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {727857}, pmid = {34712178}, issn = {1664-1078}, abstract = {When considering the numerous mindfulness-based and mindfulness-informed programs that have flourished in the past decades it is not always clear that they all refer to the same "mindfulness. " To facilitate more clarity and precision in describing, researching and teaching mindfulness in the secular settings, we propose a classification framework of mindfulness practices, intentions behind them and the experiential understandings the practices may aim to develop. Accordingly, the proposed framework, called the Mindfulness Map, has two axes. The first axis outlines mindfulness practices (and associated instructions) classified into four groups (MGs), e.g. the MG1 focuses on cultivating attention to the present moment somatic and sensory experience while the MG4 focuses on cultivating the ability to recognize and deconstruct perceptual, cognitive and emotional experiences and biases. The second axis outlines possible intentions (INTs) to cultivate particular experiential understanding (EU) via teaching and practicing the MGs, e.g., the INT1 designates the intention to gain EU of how our relationship to experience contributes to wellbeing, the INT2 refers to the intention to gain EU of the changing nature of body, mind and external phenomenon. We suggest that the same MG can lead to different EUs outcomes based on the specific INTs applied in their teaching or practice. The range of INTs and EUs included here is not exhaustive, there are further types the Map could be expanded toward. Aside from encouraging more fine-grained distinctions of mindfulness practices, the proposed Map aims to open discussions about interactions between MGs, INTs, EUs and practice outcomes. The Map may facilitate more nuanced and precise approaches to researching the range of outcomes cultivated by mindfulness practices, help bridge contradictory findings, and catalyze further debate and research into ethical aspects of mindfulness. The Map also highlights the need for further teaching development and research on longer-term trajectories of mindfulness practice. While the proposed Mindfulness Map organises the mindfulness practice territory along two axes, it is aimed as a starting point for further discussion and can be further revised and/or expanded by other axes.}, } @article {pmid34708717, year = {2021}, author = {Wang, YY and Liu, C and Chen, X and Ji, J and Zhu, SL and Sun, Q and Zhang, K and Zhu, J and Zhao, S and Wang, YW and Ma, R and Wang, JL}, title = {Heat shock protein 90α in nipple discharge as a potential tumor marker for breast cancer.}, journal = {The Chinese journal of physiology}, volume = {64}, number = {5}, pages = {251-256}, doi = {10.4103/cjp.cjp_72_21}, pmid = {34708717}, issn = {0304-4920}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; Female ; HSP90 Heat-Shock Proteins/*genetics ; Humans ; *Nipple Discharge ; }, abstract = {Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.}, } @article {pmid34707969, year = {2021}, author = {Blum, K and Bowirrat, A and Gondre Lewis, MC and Simpatico, TA and Ceccanti, M and Steinberg, B and Modestino, EJ and Thanos, PK and Baron, D and McLaughlin, T and Brewer, R and Badgaiyan, RD and Ponce, JV and Lott, L and Gold, MS}, title = {Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development.}, journal = {Current psychopharmacology}, volume = {10}, number = {}, pages = {}, pmid = {34707969}, issn = {2211-5560}, support = {I01 CX000479/CX/CSRD VA/United States ; }, abstract = {BACKGROUND: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait.

OBJECTIVE: The primary issue involves the question of whether there exists a mixed hypo or hyper-dopaminergia in this population.

METHOD: Genetic Addiction Risk Score (GARS®) testing was carried out of 24 Caucasians of ages 12-19, derived from families with RDS.

RESULTS: We have found that adolescents from this cohort, derived from RDS parents, displayed a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64%).

CONCLUSION: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly, in future studies, we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This "two-hit" approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant epidemic.}, } @article {pmid34706697, year = {2021}, author = {Kim, K and Kim, IJ and Pak, K and Kang, T and Seol, YM and Choi, YJ and Kim, H}, title = {Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative [18]F-FDG PET-CT in breast cancer: a retrospective cross-sectional study.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {1151}, pmid = {34706697}, issn = {1471-2407}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*metabolism/pathology/surgery ; Cross-Sectional Studies ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; *Insulin Resistance ; Liver/metabolism ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; *Positron Emission Tomography Computed Tomography ; Preoperative Care ; Prognosis ; Proportional Hazards Models ; Psoas Muscles/*metabolism ; Radiopharmaceuticals/*pharmacokinetics ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; Triple Negative Breast Neoplasms ; }, abstract = {BACKGROUND: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by [18]F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer.

METHODS: The medical records of 288 patients who had undergone surgical resection for stages I-III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver.

RESULTS: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS.

CONCLUSIONS: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.}, } @article {pmid34706119, year = {2022}, author = {Seyrek, N and Hollemans, E and Osanto, S and Pelger, RCM and van der Poel, HG and Bekers, E and Bangma, CH and Rietbergen, J and Roobol, MJ and Schoots, IG and van Leenders, GJLH}, title = {Cribriform architecture outperforms Gleason pattern 4 percentage and tertiary Gleason pattern 5 in predicting the outcome of Grade Group 2 prostate cancer patients.}, journal = {Histopathology}, volume = {80}, number = {3}, pages = {558-565}, pmid = {34706119}, issn = {1365-2559}, support = {//Jaap Schouten Foundation/ ; }, mesh = {Adenocarcinoma/*pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Male ; Middle Aged ; *Neoplasm Grading ; Predictive Value of Tests ; *Prognosis ; Prostatectomy ; Prostatic Neoplasms/*pathology ; }, abstract = {AIMS: Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence-free survival (BCRFS).

METHODS AND RESULTS: Of 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with ≥25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0-1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, ≥25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2-2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors.

CONCLUSION: In conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports.}, } @article {pmid34703931, year = {2021}, author = {Molaei Ramshe, S and Ghaedi, H and Omrani, MD and Geranpayeh, L and Alipour, B and Ghafouri-Fard, S}, title = {Up-regulation of FOXN3-AS1 in invasive ductal carcinoma of breast cancer patients.}, journal = {Heliyon}, volume = {7}, number = {10}, pages = {e08179}, pmid = {34703931}, issn = {2405-8440}, abstract = {Oncogenic and tumor-suppressive roles of long non-coding RNA make them an appropriate target for expression analysis in cancer studies. In this study, we selected two lncRNAs (EMX2OS and FOXN3-AS1) that are resided near the GWAS-identified SNPs for breast cancer (rs2901157 and rs141061110). These transcripts have been identified in different cancer types as either oncogenes or tumor suppressors. In the present investigation, we aimed to quantify the expression level of EMX2OS and FOXN3-AS1 in 44 breast cancer samples and normal adjacent tissues (ANCTs). The FOXN3-AS1 expression level was significantly increased in breast cancer samples compared with ANCTs (P value = 0.02), Also its amounts could distinguish two sets of samples with an accuracy of 70% (P value = 0.009). We have found an association between FOXN3-AS1 expression and tumor size (P value = 0.02). On the other hand, no significant differences were found in the EMX2OS expression level between two sets of samples (P value = 0.44); however, EMX2OS expression level has a significant association with the age of the patients (P value = 0.03). According to our result, FOXN3-AS1 can be demonstrated as a probable diagnostic marker in breast cancer so we suggest further functional studies to find the precise role of these lncRNAs in breast cancer progression.}, } @article {pmid34703443, year = {2021}, author = {Lardinois, B and Miller, L and Randazzo, A and Laurent, T and Debois, R and Henry, S}, title = {Leptomeningeal Carcinomatosis: A Call for Optimizing Diagnostic Sensitivity by the Hematology Laboratory.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {1248-1253}, pmid = {34703443}, issn = {1662-6575}, abstract = {In the cerebrospinal fluid (CSF), the demonstration of malignant cells by cytological examination is currently the gold standard for the diagnosis of leptomeningeal carcinomatosis (LC). However, a positive cytology is observed in only 50-60% of patients with LC and highly dependent on pre-analytical factors. The hematology laboratory could provide an immediate and accurate diagnosis, but diagnostic sensitivity is not always optimized once the sample is received. We hereby report a 49-year-old woman with a 3-year grade III invasive ductal carcinoma who was admitted to the emergency department due to headaches, nausea, and vomiting. The CSF revealed pleocytosis with suspicious high fluorescent cells on the hematology analyzer concomitantly with biochemical alterations. Cytomorphological examination confirmed tumor cells, thus diagnosing a leptomeningeal metastasis of her breast cancer. The patient was eventually transferred to palliative care. Cytological examination is a valuable tool for a rapid diagnosis of LC if diagnostic performance is optimized. In addition to repeated CSF collections with a sufficient volume (5-10 mL), this could be reached by processing the CSF as soon as possible, taking into account the fluorescence information from the analyzer, proceeding systematically to microscopic examination even with normal CSF white blood cell count, and providing quality improvement of the staff to identify malignant cells.}, } @article {pmid34703442, year = {2021}, author = {Goto, W and Kashiwagi, S and Kawano, Y and Komoda, A and Ishihara, S and Asano, Y and Morisaki, T and Hirakawa, K and Ohira, M}, title = {Pathological Complete Response following Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma with Mammary Paget's Disease: A Case Report.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {1242-1247}, pmid = {34703442}, issn = {1662-6575}, abstract = {Mammary Paget's disease is a rare malignancy. Mastectomy or breast-conserving surgery has been considered as the standard treatment, while there have been few reports of neoadjuvant chemotherapy (NAC). A 53-year-old woman with erythema and skin ulceration of the left breast was admitted to our institution. Breast examinations revealed left invasive ductal carcinoma (cT1bN0M0, cStage I), and a punch biopsy of the left mammary erythema indicated Paget's disease (cTisN0M0, cStage0). The patient received NAC because of multiple lesions. Consequently, the breast tumor clinically disappeared, and the erythema improved. These outcomes made it easier to perform surgery (left mastectomy and sentinel node biopsy). Histopathological examination revealed no residual cancer cells in either the mammary gland or breast skin, and no metastasis was found in the sentinel lymph node. Therefore, NAC may be a useful treatment for mammary Paget's disease.}, } @article {pmid34702413, year = {2021}, author = {Greenbaum, D}, title = {Cyberbiosecurity: An Emerging Field that has Ethical Implications for Clinical Neuroscience.}, journal = {Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees}, volume = {30}, number = {4}, pages = {662-668}, doi = {10.1017/S096318012100013X}, pmid = {34702413}, issn = {1469-2147}, mesh = {Computer Security ; Genomics ; Humans ; Morals ; *Neurosciences ; *Privacy ; }, abstract = {Cyberbiosecurity is an emerging field that relates to the intersection of cybersecurity and the clinical and research practice in the biosciences. Beyond the concerns that usually arise in the areas of genomics, this paper highlights ethical concerns raised by cyberbiosecurity in clinical neuroscience. These concerns relate not only to the privacy of the data collected by imaging devices, but also the concern that patients using various stimulatory devices can be harmed by a hacker who either obfuscates the outputs or who interferes with the stimulatory process. The paper offers some suggestions as to how to rectify these increasingly dire concerns.}, } @article {pmid34702045, year = {2021}, author = {Ilbeigi, S and Naeimzadeh, Y and Davoodabadi Farahani, M and Rafi Monjezi, M and Dastsooz, H and Daraei, A and Farahani, F and Dastgheib, A and Mansoori, Y and Tabei, SMB}, title = {Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {34}, number = {5}, pages = {382-391}, doi = {10.48095/ccko2021382}, pmid = {34702045}, issn = {1802-5307}, mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Middle Aged ; *RNA, Long Noncoding ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC.

METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done.

RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10).

CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.}, } @article {pmid34698916, year = {2022}, author = {Deshpande, SS and Malik, SC and Conforti, P and Lin, JD and Chu, YH and Nath, S and Greulich, F and Dumbach, MA and Uhlenhaut, NH and Schachtrup, C}, title = {P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.}, journal = {Cell and tissue research}, volume = {387}, number = {3}, pages = {415-431}, pmid = {34698916}, issn = {1432-0878}, support = {1442/8-1//Deutsche Forschungsgemeinschaft/ ; 1442/9-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Lateral Ventricles/metabolism ; Mice ; *Neural Stem Cells ; Neurogenesis ; Receptor, Nerve Growth Factor/metabolism ; *Stroke ; }, abstract = {Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75[NTR-/-]) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75[NTR-/-] NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75[NTR] abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75[NTR-/-] NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75[NTR-/-] NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75[NTR] abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.}, } @article {pmid34697300, year = {2021}, author = {Abel, MK and Melisko, ME and Rugo, HS and Chien, AJ and Diaz, I and Levine, JK and Griffin, A and McGuire, J and Esserman, LJ and Borno, HT and Mukhtar, RA}, title = {Decreased enrollment in breast cancer trials by histologic subtype: does invasive lobular carcinoma resist RECIST?.}, journal = {NPJ breast cancer}, volume = {7}, number = {1}, pages = {139}, pmid = {34697300}, issn = {2374-4677}, support = {K08 CA256047/CA/NCI NIH HHS/United States ; }, abstract = {Enrollment in metastatic breast cancer trials usually requires measurable lesions, but patients with invasive lobular carcinoma (ILC) tend to form diffuse disease. We found that the proportion of patients with metastatic ILC enrolled in clinical trials at our institution was significantly lower than that of patients with invasive ductal carcinoma (IDC). Possible links between requiring measurable disease and decreased enrollment of ILC patients require further study to ensure equitable trial access.}, } @article {pmid34695137, year = {2021}, author = {Opoku, F and Bedu-Addo, K and Titiloye, NA and Atta Manu, E and Ameh-Mensah, C and Duduyemi, BM}, title = {Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0258543}, pmid = {34695137}, issn = {1932-6203}, mesh = {Adult ; Aged ; *Breast Neoplasms ; Female ; Ghana ; Humans ; Middle Aged ; Retrospective Studies ; Tertiary Care Centers ; Tumor Suppressor Protein p53 ; }, abstract = {BACKGROUND: Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort.

METHOD: A 9-year retrospective cross-sectional study on archived tissue blocks-formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes.

RESULTS: The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05).

CONCLUSION: The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.}, } @article {pmid34689837, year = {2021}, author = {Rafiq, MT and Abdul Hamid, MS and Hafiz, E}, title = {The effect of rehabilitation protocol using mobile health in overweight and obese patients with knee osteoarthritis: a clinical trial.}, journal = {Advances in rheumatology (London, England)}, volume = {61}, number = {1}, pages = {63}, pmid = {34689837}, issn = {2523-3106}, mesh = {Clinical Protocols ; Humans ; Middle Aged ; *Obesity/complications ; *Osteoarthritis, Knee/rehabilitation ; *Overweight/complications ; *Telemedicine ; Treatment Outcome ; }, abstract = {OBJECTIVE: The objective of this randomized controlled trial (RCT) was to investigate the effectiveness of the lower limb rehabilitation protocol (LLRP) combined with mobile health (mHealth) applications on knee pain, mobility, functional activity and activities of daily living (ADL) among knee osteoarthritis (OA) patients who were overweight and obese.

METHODS: This study was a single-blind, RCT conducted at Teaching Bay of Rehmatul-Lil-Alameen Post Graduate Institute of Cardiology between February and November 2020. 114 knee OA patients who were overweight and obese were randomly divided by a computer-generated number into the rehabilitation group with mHealth (RGw-mHealth) to receive LLRP + instructions of daily care (IDC) combined with mHealth intervention, rehabilitation group without mHealth (RGwo-mHealth) to receive LLRP + IDC intervention and control group (CG) to receive IDC intervention. All three groups were also provided leaflets explaining about their intervention. The primary outcome measure was knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index score. The secondary outcome measures were mobility measured by the Timed up and go (TUG) test, functional activity measured by the patient-specific functional scale (PSFS), and ADL measured by the Katz Index of independence in ADL scores.

RESULTS: Among the 114 patients who were randomized (mean age, 53 years), 96 (84%) completed the trial. After 3-months of intervention, patients in all three groups had statistically significant knee pain reduction (RGw-mHealth: 2.54; RGwo-mHealth: 1.47; and CG: 0.37) within groups (P < 0.05). Furthermore, patients in the RGw-mHealth and RGwo-mHealth had statistically significant improvement in mobility, functional activity, and ADL within groups (P < 0.05), but no improvement was noted in the CG (p > 0.05). As indicated in the overall analysis of covariance, there were statistically significant differences in the mean knee pain, mobility, functional activity, and ADL changes between groups after 3-months (p < 0.001). The pairwise between-group comparisons (Bonferroni post hoc analysis) of the knee pain, mobility, functional activity, and ADL scores at 3-months revealed that patients in the RGw-mHealth had significantly higher mean change in the knee pain, TUG test, functional activity, and ADL scores compared to patients in the RGwo-mHealth or CG.

CONCLUSION: Reduction in knee pain, improvement in mobility, functional activity, and ADL were more among patients in the RGw-mHealth compared with the RGwo-mHealth or CG. Trial registration National Medical Research Registry: NMRR-20-1094-52911. Date of registration: 05-05-2020. URL: https://www.nmrr.gov.my .}, } @article {pmid34674235, year = {2021}, author = {Danon-Kraun, S and Horovitz, O and Frenkel, T and Richter-Levin, G and Pine, DS and Shechner, T}, title = {Return of fear following extinction in youth: An event-related potential study.}, journal = {Developmental psychobiology}, volume = {63}, number = {7}, pages = {e22189}, pmid = {34674235}, issn = {1098-2302}, support = {ZIA MH002781/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Brain/physiology ; Child ; Conditioning, Classical/physiology ; Evoked Potentials/physiology ; *Extinction, Psychological/physiology ; *Fear/physiology ; Humans ; }, abstract = {The ability to learn to differentiate safety from danger matures gradually, particularly when such learning occurs over an extended time period. And yet, most research on fear learning examines the early phases of such learning and mainly in adults. The current study examined fear conditioning and extinction, as well as one form of extended learning, return of fear (ROF). Thirty-three typically developing children (age range: 7-14 years) completed fear conditioning and extinction; self-reports and psychophysiological indices were measured at this point. Two weeks later, children completed a ROF test (n = 23), and event-related potentials (ERPs) were recorded. Results indicated successful fear acquisition and extinction. Moreover, participants reported greater fear of the conditioned stimulus (CS+) than the safety stimulus (CS-) in the ROF test 2 weeks later. In electrophysiology data, ROF manifested as a larger late positive potential (LPP) response to the CS+ than the CS-. Finally, these differences in LPP responses were positively correlated with poorer extinction, as indicated by the GSR responses 2 weeks earlier. This is the first ERP study to demonstrate ROF in children. The LPP measure may index an interplay between inhibitory and excitatory brain-related processes underlying the long-term effects of fear learning.}, } @article {pmid34673584, year = {2021}, author = {Senel, F}, title = {The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.}, journal = {Indian journal of pathology & microbiology}, volume = {64}, number = {4}, pages = {671-676}, doi = {10.4103/IJPM.IJPM_606_20}, pmid = {34673584}, issn = {0974-5130}, mesh = {Adult ; Age Factors ; Biomarkers, Tumor/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/*physiopathology ; Female ; Genetic Variation ; Genotype ; Humans ; Middle Aged ; Pathology, Clinical/methods ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; }, abstract = {AIM: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features.

MATERIALS AND METHODS: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded.

RESULTS AND CONCLUSIONS: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.}, } @article {pmid34672684, year = {2021}, author = {Yadav, S and Hu, C and Nathanson, KL and Weitzel, JN and Goldgar, DE and Kraft, P and Gnanaolivu, RD and Na, J and Huang, H and Boddicker, NJ and Larson, N and Gao, C and Yao, S and Weinberg, C and Vachon, CM and Trentham-Dietz, A and Taylor, JA and Sandler, DR and Patel, A and Palmer, JR and Olson, JE and Neuhausen, S and Martinez, E and Lindstrom, S and Lacey, JV and Kurian, AW and John, EM and Haiman, C and Bernstein, L and Auer, PW and Anton-Culver, H and Ambrosone, CB and Karam, R and Chao, E and Yussuf, A and Pesaran, T and Dolinsky, JS and Hart, SN and LaDuca, H and Polley, EC and Domchek, SM and Couch, FJ}, title = {Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {39}, number = {35}, pages = {3918-3926}, pmid = {34672684}, issn = {1527-7755}, support = {P01 CA087969/CA/NCI NIH HHS/United States ; R01 CA097396/CA/NCI NIH HHS/United States ; K07 CA092044/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; R01 CA225662/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 CA204819/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; R01 CA067264/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; R01 CA047147/CA/NCI NIH HHS/United States ; U01 CA082004/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genetic Testing/*methods ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {PURPOSE: To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast.

MATERIALS AND METHODS: The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC).

RESULTS: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC.

CONCLUSION: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.}, } @article {pmid34668757, year = {2021}, author = {Saelens, JW and Petersen, JEV and Freedman, E and Moseley, RC and Konaté, D and Diakité, SAS and Traoré, K and Vance, N and Fairhurst, RM and Diakité, M and Haase, SB and Taylor, SM}, title = {Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0075521}, pmid = {34668757}, issn = {2379-5042}, support = {R21 AI125988/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hemoglobin A/*genetics ; Hemoglobin, Sickle/*genetics ; Hemoglobins/metabolism ; Humans ; Malaria, Falciparum/blood/*genetics/parasitology ; Male ; Plasmodium falciparum/physiology ; Sickle Cell Trait/blood/*genetics/parasitology ; Transcriptional Activation ; }, abstract = {Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both in vitro cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During in vitro cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen in vitro and in vivo indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. IMPORTANCE Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in in vitro time series experiments and in vivo samples from natural infections. Our in vitro time series data reveal that, during its blood stage, P. falciparum's gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our in vitro and in vivo data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.}, } @article {pmid34666229, year = {2021}, author = {Barsha, NA and Rahman, A and Mahdy, MRC}, title = {Automated detection and grading of Invasive Ductal Carcinoma breast cancer using ensemble of deep learning models.}, journal = {Computers in biology and medicine}, volume = {139}, number = {}, pages = {104931}, doi = {10.1016/j.compbiomed.2021.104931}, pmid = {34666229}, issn = {1879-0534}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Deep Learning ; Diagnosis, Computer-Assisted ; Female ; Humans ; Survival Rate ; }, abstract = {Invasive ductal carcinoma (IDC) breast cancer is a significant health concern for women all around the world and early detection of the disease may increase the survival rate in patients. Therefore, Computer-Aided Diagnosis (CAD) based systems can assist pathologists to detect the disease early. In this study, we present an ensemble model to detect IDC using DenseNet-121 and DenseNet-169 followed by test time augmentation (TTA). The model achieved a balanced accuracy of 92.70% and an F1-score of 95.70% outperforming the current state-of-the-art. Comparative analysis against various pre-trained deep learning models and preprocessing methods have been carried out. Qualitative analysis has also been conducted on the test dataset. After the detection of IDC breast cancer, it is important to grade it for further treatment. In our study, we also propose an ensemble model for the grading of IDC using the pre-trained DenseNet-121, DenseNet-201, ResNet-101v2, and ResNet-50 architectures. The model is inferred from two validation cohorts. For the patch-level classification, the model yielded an overall accuracy of 69.31%, 75.07%, 61.85%, and 60.50% on one validation cohort and 62.44%, 79.14%, 76.62%, and 71.05% on the second validation cohort for 4×, 10×, 20×, and 40× magnified images respectively. The same architecture is further validated using a different IDC dataset where it achieved an overall accuracy of 90.07%. The performance of the models on the detection and grading of IDC shows that they can be useful to help pathologists detect and grade the disease.}, } @article {pmid34665029, year = {2022}, author = {Foesleitner, O and Sulaj, A and Sturm, V and Kronlage, M and Godel, T and Preisner, F and Nawroth, PP and Bendszus, M and Heiland, S and Schwarz, D}, title = {Diffusion MRI in Peripheral Nerves: Optimized b Values and the Role of Non-Gaussian Diffusion.}, journal = {Radiology}, volume = {302}, number = {1}, pages = {153-161}, doi = {10.1148/radiol.2021204740}, pmid = {34665029}, issn = {1527-1315}, mesh = {Adult ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*physiopathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Male ; Middle Aged ; Peripheral Nerves/*diagnostic imaging/*physiopathology ; Prospective Studies ; Reproducibility of Results ; }, abstract = {Background Diffusion-weighted imaging (DWI) provides specific in vivo information about tissue microstructure, which is increasingly recognized for various applications outside the central nervous system. However, standard sequence parameters are commonly adopted from optimized central nervous system protocols, thus potentially neglecting differences in tissue-specific diffusional behavior. Purpose To characterize the optimal tissue-specific diffusion imaging weighting scheme over the b domain in peripheral nerves under physiologic and pathologic conditions. Materials and Methods In this prospective cross-sectional study, 3-T MR neurography of the sciatic nerve was performed in healthy volunteers (n = 16) and participants with type 2 diabetes (n = 12). For DWI, 16 b values in the range of 0-1500 sec/mm[2] were acquired in axial and radial diffusion directions of the nerve. With a region of interest-based approach, diffusion-weighted signal behavior as a function of b was estimated using standard monoexponential, biexponential, and kurtosis fitting. Goodness of fit was assessed to determine the optimal b value for two-point DWI/diffusion tensor imaging (DTI). Results Non-Gaussian diffusional behavior was observed beyond b values of 600 sec/mm[2] in the axial and 800 sec/mm[2] in the radial diffusion direction in both participants with diabetes and healthy volunteers. Accordingly, the biexponential and kurtosis models achieved a better curve fit compared with the standard monoexponential model (Akaike information criterion >99.9% in all models), but the kurtosis model was preferred in the majority of cases. Significant differences between healthy volunteers and participants with diabetes were found in the kurtosis-derived parameters Dk and K. The results suggest an upper bound b value of approximately 700 sec/mm[2] for optimal standard DWI/DTI in peripheral nerve applications. Conclusion In MR neurography, an ideal standard diffusion-weighted imaging/diffusion tensor imaging protocol with b = 700 sec/mm[2] is suggested. This is substantially lower than in the central nervous system due to early-occurring non-Gaussian diffusion behavior and emphasizes the need for tissue-specific b value optimization. Including higher b values, kurtosis-derived parameters may represent promising novel imaging markers of peripheral nerve disease. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jang and Du in this issue.}, } @article {pmid34660022, year = {2021}, author = {Koseci, T and Haksöyler, V and Olgun, P and Koyuncu, MB and Bozkurt Duman, B and Çil, T}, title = {Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e17812}, pmid = {34660022}, issn = {2168-8184}, abstract = {Background and objective Male breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients. Materials and methods We retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded. Results The mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4. Conclusion The hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.}, } @article {pmid34659834, year = {2021}, author = {Ntirenganya, F and Twagirumukiza, JD and Bucyibaruta, G and Rugwizangoga, B and Rulisa, S}, title = {Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.}, journal = {International journal of breast cancer}, volume = {2021}, number = {}, pages = {5560559}, pmid = {34659834}, issn = {2090-3170}, abstract = {BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women.

OBJECTIVES: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda.

METHODS: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis.

RESULTS: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI 2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI 4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI 3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI 1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI 1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype.

CONCLUSION: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.}, } @article {pmid34659414, year = {2021}, author = {Alkhathami, AG and Verma, AK and Alfaifi, M and Kumar, L and Alshahrani, MY and Hakami, AR and Alshehri, OM and Asiri, M and Ali Beg, MM}, title = {Role of miRNA-495 and NRXN-1 and CNTN-1 mRNA Expression and Its Prognostic Importance in Breast Cancer Patients.}, journal = {Journal of oncology}, volume = {2021}, number = {}, pages = {9657071}, pmid = {34659414}, issn = {1687-8450}, abstract = {Breast cancer is a heterogeneous disease in which genetic factors are involved in disease worsening and higher mortality. Epidemiological and clinical research revealed that breast cancer incidence continues to rise. 100 histopathologically confirmed untreated newly diagnosed cases of invasive ductal carcinoma (IDC) of breast and 100 healthy subjects were involved and blood samples were collected in non-EDTA plain vials. Serum was separated by centrifugation, total RNA was extracted from serum, and cDNA synthesis was done to study the miRNA-495 and neurexin-1 (NRXN-1) and contactin 1 (CNTN-1) mRNA expression by QRT-PCR. The expression levels of miRNA-495, NRXN-1, and CNTN-1 were expressed in fold change. The present study observed decreased relative miRNA-495 expression (0.07-fold) while an increase in NRXN-1 (11.61-fold) and CNTN-1 (4.92-fold) was observed among breast cancer patients compared to healthy controls. A significant difference was observed in miRNA-495 expression with menopausal status (p=0.0001) and TNM stages (p=0.02). It was observed that NRXN-1 expression was significantly associated with menopausal status (p=0.03), lymph node involvement (p < 0.0001), estrogen receptor (ER) status (p=0.03), progesterone receptor (PR) status (p=0.005), TNM stages (p < 0.0001), and distant metastases (p < 0.0001). CNTN-1 expression was also found to be associated with lymph node involvement (p=0.01), PR status (p=0.03), HER2 status (p=0.04), TNM stages (p < 0.0001), and distant metastases (p < 0.0001). ROC suggested that NRXN-1 and CNTN-1 could be the important predictive marker for disease advancement and distant organ metastases. The study concluded that the decreased expression of miR-495 observed in breast cancer patients showed a negative correlation with NRXN-1 while the increased expression of NRXN-1 and CNTN-1 was linked with disease advancement and distant metastases and could be the important predictive marker for breast cancer patients.}, } @article {pmid34658590, year = {2021}, author = {Rathod, V and Jha, CK and Sinha, U and Singh, PK and Kumar, A and Bhadani, PP and Kumar, M}, title = {First Comprehensive Report of Clinicopathological Profile of Breast Cancer from Bihar, India.}, journal = {Indian journal of surgical oncology}, volume = {12}, number = {3}, pages = {598-602}, pmid = {34658590}, issn = {0975-7651}, abstract = {Only a few countries of the world have a population more than Bihar, but due to the lack of a cancer registry, authentic research, and publications, data regarding the clinicopathological characteristics of breast cancer patients from this state are scarce. The present study was aimed to report the clinicopathological characteristics of breast cancer patients at a tertiary care center in Bihar, India. This is a retrospective review of a prospectively maintained database of patients of breast cancer treated between January-2018 and March-2020. One hundred fifteen patients with breast carcinoma were included of which 112 (97.4%) were women. The mean age was 47.28 ± 11.62 years and 54.5% of women were postmenopausal. Most patients had a clinical stage of II or III (44.5% each) while 8.7% of patients had stage IV disease. Invasive ductal carcinoma no special type (IDC-NST) was the most common histology (85.2%). The majority of tumors were grade II (55.6%), lymphovascular invasion was seen in 45.6%, and perineural invasion in 18.4%. Estrogen receptor was found in 41.8%, progesterone receptor was positive in 47.3%, and human epidermal growth factor receptor-2 (HER-2/Neu) overexpression was observed in 39.8%. Triple-negative breast cancer was found in 26.2% of patients. The majority underwent mastectomy (71.3%) while breast conservation was done in 26%. All except one patient underwent axillary lymph node dissection for axillary staging. 43.5% patients received neoadjuvant chemotherapy, 52.9% received adjuvant chemotherapy, while 3.5% patients received palliative chemotherapy. The clinicopathological profile of breast cancer patients from Bihar is similar to that reported from other parts of India except for a lower rate of distant metastasis.}, } @article {pmid34657058, year = {2021}, author = {Takagi, H and Fukai, H and Misawa, S and Kurogochi, A and Kirii, Y}, title = {[A Case of Bone Marrow Carcinomatosis Associated with Breast Cancer with Anemia and Thrombocytopenia Successfully Treated with Aromatase Inhibitor Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {10}, pages = {1255-1257}, pmid = {34657058}, issn = {0385-0684}, mesh = {*Anemia/drug therapy/etiology ; Aromatase Inhibitors ; Bone Marrow ; *Breast Neoplasms/complications/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Peritoneal Neoplasms ; *Thrombocytopenia/drug therapy/etiology ; }, abstract = {The patient was a 61-year-old woman who presented to the hospital with the chief complaints of anemia and thrombocytopenia. There was a mass in her left breast, and a needle biopsy with pathology revealed invasive ductal carcinoma, which was HR-positive and HER2-negative. A PET scan revealed multiple bone metastases, which were confirmed on bone marrow biopsy, leading to the diagnosis of bone marrow carcinomatosis. As the patient was in good general condition, an aromatase inhibitor(AI)therapy was selected. Rapid improvements in her hemoglobin level and platelet count were observed. At 19 months after the start of treatment, we were able to perform a left mastectomy with left axillary lymph node dissection. The histological evaluation of her response to treatment was Grade 2a, and severe lymph node metastasis was observed. The patient continued to receive the AI postoperatively. Thirty-two months after the start of treatment, there was no evidence of cancer on clinical imaging. Although it is rare for bone marrow carcinomatosis to occur, as in the present case, it is also notable that the patient had been in long-term remission with consistent AI therapy.}, } @article {pmid34654324, year = {2021}, author = {Han, Y and Wang, J and Wang, Z and Xu, B}, title = {Clinicopathological Characteristics and Prognosis of Squamous Cell Carcinoma of the Breast: A Population-Based Analysis.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {28}, number = {}, pages = {10732748211044355}, pmid = {34654324}, issn = {1526-2359}, mesh = {Age Factors ; Aged ; Breast Neoplasms/*mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/pathology ; Carcinoma, Squamous Cell/*mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Propensity Score ; Prospective Studies ; Receptor, ErbB-2/biosynthesis ; SEER Program ; Sex Factors ; Triple Negative Breast Neoplasms/mortality/pathology ; }, abstract = {BACKGROUND: To better understand the clinicopathological features and prognostic profiles of squamous cell carcinoma (SCC) of the breast.

METHODS: Information on breast cancer was obtained from the Surveillance, Epidemiology, and End Results database (2004-2016). Comparative analyses were carried out to investigate the heterogeneity in the clinicopathological characteristics and survival outcomes between SCC and invasive ductal carcinoma (IDC), while propensity score matching was conducted to analyze the variations among baseline characteristics. Prognostic factors for SCC of the breast were successively identified using Cox regression analysis.

RESULTS: A total of 382 SCC patients and 561477 IDC patients were identified in this study. Comparatively, the SCC cohort exhibited a higher proportion of male individuals, poor differentiation, an advanced TNM stage, an increasing percentage of triple-negative (TN) subtype, an increasing rate of organ involvement, and less access to therapeutics. The aggressive profile was consistent in the TN subgroup, with a significantly higher proportion in SCC than in IDC (25.7% vs 6.8%). Prognosis of SCC was profoundly poorer than that of IDC (mOS, 78.6 months and 121.6 months, P < .0001; mBCSS 91.9 months vs 135.6 months, P < .0001), of which the inferior tendency remained stable among disease stage and therapeutic options, while no difference was detected in the 2 subgroups with the TN subtype. The 2-year survival rate was 66.9% and the 5-year survival rate was 51.4%, with the risk factors being older age, bilateral disease, advanced TNM stage, bone and visceral involvement, surgical intervention, radiation treatment, and chemotherapy.

CONCLUSIONS: This study systematically analyzed the heterogeneous characteristics of SCC of the breast in comparison with IDC. Squamous cell breast cancer presented with increasing aggressive behavior and inferior prognosis. Prospective studies should focus on this subgroup and introduce individualized therapeutic protocols in clinical practice.}, } @article {pmid34652983, year = {2022}, author = {Ferber, SG and Weller, A and Maor, R and Feldman, Y and Harel-Fisch, Y and Mikulincer, M}, title = {Perceived social support in the social distancing era: the association between circles of potential support and COVID-19 reactive psychopathology.}, journal = {Anxiety, stress, and coping}, volume = {35}, number = {1}, pages = {58-71}, doi = {10.1080/10615806.2021.1987418}, pmid = {34652983}, issn = {1477-2205}, mesh = {Adult ; Anxiety Disorders/epidemiology ; *COVID-19 ; Communicable Disease Control ; Humans ; Pandemics ; Physical Distancing ; SARS-CoV-2 ; Social Support ; }, abstract = {BACKGROUND AND OBJECTIVES: Stressors related to the COVID-19 pandemic are risk factors for psychopathology, but psychosocial protective factors might play a crucial role in buffering the pathogenic effects of the outbreak.

DESIGN: In the current study, we examined the association of inner resources and potential external sources of support for coping with the pandemic and related lockdowns to mental health during the pandemic, while controlling for sociodemographic variables as covariates.

METHODS: We tested the model in a probability-based internet survey of a representative sample of the Israeli adult population (N = 812) conducted during the COVID-19 pandemic.

RESULTS: Perceived support in close relationships was negatively associated with the intensity of depression, anxiety, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Larger rings of potential support such as perceived belongingness to a community and trust in government were also negatively related to anxiety and depression but were positively associated with the intensity of OCD and PTSD.

CONCLUSIONS: Findings support the "tend and befriend" theory in the social distancing era and highlight the importance of keeping personal relationships alive when facing a mass trauma.}, } @article {pmid34651113, year = {2021}, author = {Çakır, Y and Kelten Talu, C and Mermut, Ö and Can Trabulus, D and Arslan, E}, title = {The Expression of Galectin-3 in Tumor and Cancer-Associated Fibroblasts in Invasive Micropapillary Breast Carcinomas: Relationship with Clinicopathologic Parameters.}, journal = {European journal of breast health}, volume = {17}, number = {4}, pages = {341-351}, pmid = {34651113}, issn = {2587-0831}, abstract = {OBJECTIVE: Galectin-3 affects tumor progression and cell surface polarization by expressing from the tumor and cancer-associated fibroblasts (CAFs). Therefore, it may have a role on micropapillary carcinomas (IMPC), which have characteristic morphological features. The aim was to investigate the expression levels of Galectin-3 within tumor and peritumoral CAFs in IMPC, and to compare with expression in invasive ductal carcinomas (IDC).

MATERIALS AND METHODS: Hematoxylin and Eosin-stained preparations of resection materials examined between 2010-2016 were re-evaluated. Thirty-four IMPC cases and 34 IDC cases with similar molecular subtype distribution to IMPC were compared. Galectin-3 levels were evaluated with a calculated H-score in tumor and semi-quantitatively in CAFs.

RESULTS: While tumoral Galectin-3 expression levels were higher in IMPCs compared to IDCs, there was no difference for Galectin-3 expression in CAFs between the two histologic types. However, there was no significant relationship between tumoral Galectin-3 expression and clinicopathological parameters in IMPCs. When the subjects were divided into two groups, depending on their Galectin-3 status regardless of histological types, the loss of Galectin-3 expression in tumor was found to be related to larger tumor size/advanced pT stage and a greater number of metastatic nodes. Additionally, expression of Galectin-3 in CAFs was found to be associated with distant metastasis.

CONCLUSION: IMPC showed prominent Galectin-3 expression in tumor compared to IDC. However, independent from the histological type, whereas the loss of Galectin-3 expression in tumor showed an association with larger tumor size and higher number of metastatic axillary lymph nodes, the presence of Galectin-3 expression in CAFs showed an association with distant metastasis.}, } @article {pmid34650520, year = {2021}, author = {Muley, C and Kotschi, S and Bartelt, A}, title = {Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {739021}, pmid = {34650520}, issn = {1664-2392}, mesh = {Adipocytes, Brown/*metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Cell Line ; Endoplasmic Reticulum Stress/physiology ; Mice ; Proteasome Endopeptidase Complex/metabolism ; Proteostasis/*physiology ; Thermogenesis/*physiology ; Ubiquitins/*metabolism ; Uncoupling Protein 1/metabolism ; }, abstract = {The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis.}, } @article {pmid34645713, year = {2021}, author = {Teodorescu, K and Plonsky, O and Ayal, S and Barkan, R}, title = {Frequency of enforcement is more important than the severity of punishment in reducing violation behaviors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {42}, pages = {}, pmid = {34645713}, issn = {1091-6490}, mesh = {COVID-19/*prevention & control/virology ; Decision Making ; Humans ; Probability ; *Punishment ; SARS-CoV-2/isolation & purification ; }, abstract = {External enforcement policies aimed to reduce violations differ on two key components: the probability of inspection and the severity of the punishment. Different lines of research offer different insights regarding the relative importance of each component. In four studies, students and Prolific crowdsourcing participants (Ntotal = 816) repeatedly faced temptations to commit violations under two enforcement policies. Controlling for expected value, we found that a policy combining a high probability of inspection with a low severity of fines (HILS) was more effective than an economically equivalent policy that combined a low probability of inspection with a high severity of fines (LIHS). The advantage of prioritizing inspection frequency over punishment severity (HILS over LIHS) was greater for participants who, in the absence of enforcement, started out with a higher violation rate. Consistent with studies of decisions from experience, frequent enforcement with small fines was more effective than rare severe fines even when we announced the severity of the fine in advance to boost deterrence. In addition, in line with the phenomenon of underweighting of rare events, the effect was stronger when the probability of inspection was rarer (as in most real-life inspection probabilities) and was eliminated under moderate inspection probabilities. We thus recommend that policymakers looking to effectively reduce recurring violations among noncriminal populations should consider increasing inspection rates rather than punishment severity.}, } @article {pmid34644211, year = {2021}, author = {Guan, X and Dong, Y and Fan, Z and Zhan, Y and Xie, X and Xu, G and Zhang, Y and Guo, G and Shi, A}, title = {Aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases is an independent prognostic factor in ALDH1-positive breast cancer.}, journal = {The Journal of international medical research}, volume = {49}, number = {10}, pages = {3000605211047279}, pmid = {34644211}, issn = {1473-2300}, mesh = {Aldehyde Dehydrogenase 1 Family ; Axilla ; *Breast Neoplasms ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Prospective Studies ; Retrospective Studies ; }, abstract = {OBJECTIVE: To determine whether aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases in patients with breast cancer is associated with poor clinical prognosis.

METHODS: This retrospective study reviewed data from the medical records of patients with immunohistochemistry-confirmed invasive ductal carcinoma (IDC) and 1-3 metastatic lymph nodes in the ipsilateral axilla between December 2012 and July 2015. The association between ALDH1 immunostaining in axillary lymph node metastases and clinical parameters and prognosis was analysed using χ[2]-test, Kaplan-Meier survival analysis, univariate and multivariate Cox regression analyses.

RESULTS: A total of 229 patients with IDC were enrolled in the study. The median follow-up was 61 months (range, 20-89 months). Patients with ALDH1-positive axillary lymph node metastases had significantly shorter relapse-free survival and overall survival compared with those with ALDH1-negative axillary lymph node metastases. ALDH1 immunostaining in axillary lymph node metastases was a significant predictor of poor prognosis in univariate and multivariate analyses.

CONCLUSION: This large study with long-term follow-up suggests that ALDH1 immunostaining in axillary lymph node metastases is an independent predictor of poor prognosis in patients with breast cancer. The clinical relevance of this finding should be confirmed in further well-designed prospective studies.}, } @article {pmid34640879, year = {2021}, author = {Yeo, J and Lee, JI and Kwon, Y}, title = {Humidity-Sensing Chipless RFID Tag with Enhanced Sensitivity Using an Interdigital Capacitor Structure.}, journal = {Sensors (Basel, Switzerland)}, volume = {21}, number = {19}, pages = {}, pmid = {34640879}, issn = {1424-8220}, support = {2018R1D1A1B07046040//National Research Foundation of Korea/ ; }, abstract = {An eight-bit chipless radio frequency identification tag providing humidity sensing and identification information is proposed. A compact, enhanced-sensitivity resonator based on an interdigital capacitor (IDC) structure is designed for humidity sensing, whereas seven electric-field-coupled inductor capacitor (ELC) resonators are used for identification information. These eight resonators are placed in a two-by-four array arrangement. A step-by-step investigation for the effect of varying the number of elements and array configuration on the resonant frequency and radar cross-section (RCS) magnitude of the IDC resonator is conducted. The RCS value of the resonant peak frequency for the IDC resonator increases as the number of array elements placed nearby increases due to the mutual coupling among the elements, and the increase in the RCS value becomes larger as the number of arrays increases in the vertical direction. Polyvinyl alcohol (PVA) is coated on the IDC-based resonator at a thickness of 0.02 mm. A non-reflective temperature and humidity chamber is fabricated using Styrofoam, and the relative humidity (RH) is varied from 50% to 80% in 10% intervals at 25 °C in order to measure a bistatic RCS of the proposed tag. The humidity sensing performance of the IDC resonator in the proposed tag is measured by the shift in the resonant peak frequency and the RCS value, and is compared with a single ELC resonator. Experiment results show that when RH increased from 50% to 80%, the sensitivities of both the resonant peak frequency and the RCS value of the IDC resonator were better than those of the ELC resonator. The variation in the RCS value is much larger compared to the resonant peak frequency for both IDC and ELC resonators. In addition, the resonant peak frequency and RCS value of the PVA-coated IDC-based resonator change, whereas those of the other seven resonators without a PVA coating do not change.}, } @article {pmid34638022, year = {2021}, author = {Liu, L and Zhao, D and Yu, F and Heidari, AA and Ru, J and Chen, H and Mafarja, M and Turabieh, H and Pan, Z}, title = {Performance optimization of differential evolution with slime mould algorithm for multilevel breast cancer image segmentation.}, journal = {Computers in biology and medicine}, volume = {138}, number = {}, pages = {104910}, doi = {10.1016/j.compbiomed.2021.104910}, pmid = {34638022}, issn = {1879-0534}, mesh = {Algorithms ; *Breast Neoplasms/diagnostic imaging ; Entropy ; Female ; Humans ; Image Processing, Computer-Assisted ; }, abstract = {Breast cancer is one of the most dangerous diseases for women's health, and it is imperative to provide the necessary diagnostic assistance for it. The medical image processing technology is one of the most critical of all complementary diagnostic technologies. Image segmentation is the core step of image processing, where multilevel image segmentation is considered one of the most efficient and straightforward methods. Many multilevel image segmentation methods based on evolutionary and population-based methods have been proposed in recent years, but many have the fatal weakness of poor convergence accuracy and the tendency to fall into local optimum. Therefore, to overcome these weaknesses, this paper proposes a modified differential evolution (MDE) algorithm with a vision based on the slime mould foraging behavior, where the recently proposed slime mould algorithm (SMA) inspires it. Besides, to obtain high-quality breast cancer image segmentation results, this paper also develops an excellent MDE-based multilevel image segmentation model, the core of which is based on non-local means 2D histogram and 2D Kapur's entropy. To effectively validate the performance of the proposed method, a comparison experiment between MDE and its similar algorithms was first carried out on IEEE CEC 2014. Then, an initial validation of the MDE-based multilevel image segmentation model was performed by utilizing a reference image set. Finally, the MDE-based multilevel image segmentation model was compared with peers using breast invasive ductal carcinoma images. A series of experimental results have proved that MDE is an evolutionary algorithm with high convergence accuracy and the ability to jump out of the local optimum, as well as effectively demonstrated that the developed model is a high-quality segmentation method that can provide practical support for further research of breast invasive ductal carcinoma pathological image processing.}, } @article {pmid34634790, year = {2021}, author = {Hung, CC and Huang, HI and Hung, CM and Moi, SH}, title = {Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study.}, journal = {Public health genomics}, volume = {}, number = {}, pages = {1-10}, doi = {10.1159/000519140}, pmid = {34634790}, issn = {1662-8063}, abstract = {INTRODUCTION: Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival.

METHODS: The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes.

RESULTS: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall -survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51-28.7, p = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group.

CONCLUSIONS: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.}, } @article {pmid34634714, year = {2021}, author = {Kufel, WD and Mastro, KA and Steele, JM and Wang, D and Riddell, SW and Paolino, KM and Thomas, SJ}, title = {Impact of a pharmacist-facilitated, evidence-based bundle initiative on Staphylococcus aureus bacteremia management.}, journal = {Diagnostic microbiology and infectious disease}, volume = {101}, number = {4}, pages = {115535}, doi = {10.1016/j.diagmicrobio.2021.115535}, pmid = {34634714}, issn = {1879-0070}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship ; Bacteremia/*drug therapy/microbiology ; Female ; Humans ; Male ; Middle Aged ; *Patient Care Bundles ; Patient Compliance ; *Pharmacists ; Referral and Consultation ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/drug effects/isolation & purification ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).

METHODS: This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.

RESULTS: Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.

CONCLUSIONS: Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.}, } @article {pmid34631552, year = {2021}, author = {Zhang, H and Zhao, Y and Liu, X and Fu, L and Gu, F and Ma, Y}, title = {High Expression of Complement Component C7 Indicates Poor Prognosis of Breast Cancer and Is Insensitive to Taxane-Anthracycline Chemotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {724250}, pmid = {34631552}, issn = {2234-943X}, abstract = {BACKGROUND: Breast cancer is the most commonly diagnosed cancer worldwide. However, the well-known biomarkers are not enough to meet the needs of precision medicine. Novel targets are desirable and highly valuable for improved patient survival. In this regard, we identified complement component C7 as one of the candidates based on data from the OCOMINE database.

METHODS: C7 expression was examined by immunohistochemistry in 331 cases of invasive ductal carcinoma (IDC), 45 cases of ductal carcinoma in situ (DCIS), and 52 cases of non-neoplastic tissues adjacent to tumor. Then, C7 expression was further confirmed by Western blot analysis based on IDC specimens and non-neoplastic breast specimens. The relationship between the C7 expression and prognosis of breast cancer patients was analyzed in order to investigate the function of C7 in breast cancer patients. Meanwhile, we also analyzed the relationship between the C7 expression and prognosis of 149 patients treated with conventional TE (taxane and anthracycline)-based chemotherapy. Then, a cohort of patients (22 cases) treated with TE neoadjuvant chemotherapy was used to further confirm the relationship between the C7 expression and TE-based chemosensitivity.

RESULTS: In our present study, we reported for the first time that C7 was an independent prognostic factor of breast cancer and C7 expression of IDC tissues was higher than non-neoplastic tissues adjacent to tumor and DCIS. In a cohort of 331 IDC patients, high expression of C7 indicated poor prognosis especially in the triple negative subtype and luminal B subtype. Furthermore, C7 was also a promoting factor for triple negative subtype patients to develop bone metastasis. Meanwhile, we provided the first evidence that patients with high C7 expression were insensitive to TE (taxane and anthracycline)-based chemotherapy by analyzing a cohort of 149 patients treated with TE-based chemotherapy and another cohort of 22 patients treated with TE neoadjuvant chemotherapy.

CONCLUSIONS: In summary, high expression of C7 may promote breast cancer development and might be insensitive to TE-based chemotherapy. Our present study laid a foundation to help clinicians improve the identification of patients for TE-based chemotherapy by C7 in the era of precision medicine.}, } @article {pmid34631542, year = {2021}, author = {Zhang, Q and Agyekum, EA and Zhu, L and Yan, L and Zhang, L and Wang, X and Yin, L and Qian, X}, title = {Clinical Value of Three Combined Ultrasonography Modalities in Predicting the Risk of Metastasis to Axillary Lymph Nodes in Breast Invasive Ductal Carcinoma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {715097}, pmid = {34631542}, issn = {2234-943X}, abstract = {OBJECTIVE: The present study aimed to assess the clinical value of conventional ultrasound (C-US), ultrasound elastography (UE), percutaneous contrast-enhanced ultrasound (P-CUES), and the combination of these three ultrasonography modalities for evaluating the risk of axillary lymph node (ALN) metastasis in breast invasive ductal carcinoma (IDC).

METHODS: This retrospective analysis included 120 patients with pathologically confirmed IDC who underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Based on the gold standard of postoperative pathology, ALN pathology results were evaluated and compared with findings obtained using C-US, UE, P-CUES, and the three modalities combined.

RESULTS: (1) There was a statistically significant difference between the histological grade of the tumor and the pathological condition of ALNs. (2) The difference between C-US parameters and UE score were statistically significant. The accuracy of P-CEUS localization of SLNs was 100% (96/96) when compared with localization guided by methylene blue. The difference in the distribution of the four SLN enhancement patterns was statistically significant. (3) The sensitivity, specificity, positive predictive value, and negative predictive value of C-US and UE were 75%, 71%, 58%, and 89%, and 71%, 72%, 50%, and 86%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of P-CUES were 91%, 82%, 78%, 92%, respectively. When all three modalities were combined, the sensitivity, specificity, positive predictive value, and negative predictive value were 94%, 89%, 86%, and 95%, respectively. In the detection of ALN metastasis, there was a good correlation between histopathological results and evaluations based on the three combined ultrasonography modalities (kappa: 0.82, p<0.001).

CONCLUSIONS: When compared to C-US, UE, or P-CEUS alone, the combination of the three ultrasonography modalities was found to be superior in distinguishing metastatic and non-metastatic ALNs. This combined strategy may aid physicians in determining the most appropriate approach to ALN surgery as well as the prognosis of breast IDC.}, } @article {pmid34629562, year = {2021}, author = {Días, R and Mendes, ÂB and Lages, N and Machado, H}, title = {[Ultrasound-guided fascial plane blocks as unique anesthetic technique for total mastectomy in a covid-19 era: a case report].}, journal = {Revista espanola de anestesiologia y reanimacion}, volume = {68}, number = {7}, pages = {408-413}, pmid = {34629562}, issn = {2340-3284}, abstract = {INTRODUCTION: Regional anesthesia techniques were recently introduced to provide analgesia for breast surgery. These techniques are rarely used as the primary anesthesia due to the complexity of breast innervation, with numerous structures that can potentially be disrupted during breast surgery.

CASE REPORT: A female patient in her sixties diagnosed with invasive ductal carcinoma on her left breast was scheduled for a simple mastectomy. After anesthetic evaluation, identification of high risk perioperative cardiovascular complications, it was proposed to perform the surgery only with regional anesthesia. A combination of pectoral nerve block (Pecs II), pecto-intercostal fascial block (PIFB) and supraclavicular nerve block ultrasound-guided were successfully performed.

CONCLUSION: This is the first case reporting a novel approach in a patient with severe cardiopulmonary disease who underwent breast surgery in a COVID-19 era.}, } @article {pmid34624832, year = {2021}, author = {Mohammed, AA}, title = {The clinical behavior of different molecular subtypes of breast cancer.}, journal = {Cancer treatment and research communications}, volume = {29}, number = {}, pages = {100469}, doi = {10.1016/j.ctarc.2021.100469}, pmid = {34624832}, issn = {2468-2942}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous group of tumors classified, according to different gene expressions that encodes for the hormone receptor status, into 4 main categories which are: luminal types A and B, triple negative/basal-like, and Her-2 molecular subtypes.

PATIENTS AND METHODS: This retrospective study included 311 breast cancer females. Patients were classified according to the expression of hormone receptors into: Luminal-A, luminal-B, HER-2 enriched and basal-like types. All groups were then studied for differences in clinical course of the disease.

RESULTS: Luminal-B type was the commonest molecular type (43.73%). Invasive ductal carcinoma was the commonest histological type (89.1%). Stages IIB and IIIA were the commonest clinical stages (24.4% & 22.2%) respectively. Most patients had no recurrence (85.5%), the commonest recurrence was local and axillary ones (7.1%). Low grade tumors were less frequent than intermediate and high grades (3.5%, 51.1%, and 45.3%). We found a significant correlation between molecular subtypes and survival status, tumor grade, and histopathological types (P values 0.029, 0.001, and 0.006) respectively, while it was not significant with age, BMI, recurrence & metastatic disease, overall survival, and TNM stage (P values 0.648, 0.398, 0.5, 0.063 and 0.319).

CONCLUSION: Luminal types A and B are the commonest molecular subtypes of breast cancer. Luminal type A is associated with improved survival, and basal like has the highest breast cancer fatality rates. Invasive ductal carcinomas of specific types mostly found in patients with luminal types A and B, while other rare forms like Paget's disease was diagnosed HER-2 enriched types.}, } @article {pmid34623274, year = {2022}, author = {Khurana, D and Vikas, and Shaw, AK and Soni, S}, title = {Polydopamine Coated Gold Nano Blackbodies for Tumor-Selective Spatial Thermal Damage During Plasmonic Photothermal Cancer Therapy.}, journal = {IEEE transactions on nanobioscience}, volume = {21}, number = {4}, pages = {482-489}, doi = {10.1109/TNB.2021.3118895}, pmid = {34623274}, issn = {1558-2639}, mesh = {*Gold ; Humans ; Indoles ; *Neoplasms/therapy ; Polymers ; }, abstract = {Plasmonic photothermal therapy (PPTT), which involves nanoparticles and near-infrared radiation (NIR) to generate confined heat, is a potential technique for selective thermal damage of cancerous tissue. Herein, tumor-selective spatial damage characteristics during polydopamine (PDA) coated gold nano blackbodies (AuNBs) mediated PPTT is investigated through a tumor-tissue mimicking phantom. The spatial temperatures during PPTT were measured within the phantom mimicking the optical scattering of superficial invasive ductal carcinoma (injected with AuNBs) surrounded by a region without AuNBs. The phantom was irradiated using broadband NIR radiation (754-816 nm), and spatial temperatures were measured using thermocouples and an infrared thermal camera. The obtained results demonstrate that the tumor region's temperature was elevated to >50°C in about 2.5 minutes and was maintained thereafter for about 6 minutes, which is well sufficient for the thermal ablation of the tumor. While for the region surrounding the tumor, a temperature of about 40-44°C was attained, which is within safe limits for the said exposure duration. Overall, this study demonstrates that for the considered experimental parameters and tumor dimensions, heat-based thermal damage could be confined to the nanoparticle embedded tumor region while maintaining the safe temperature levels for the surrounding region, i.e., 2 mm beyond the tumor boundary.}, } @article {pmid34621293, year = {2021}, author = {Li, J and Du, J and Wang, Y and Jia, H}, title = {A Coagulation-Related Gene-Based Prognostic Model for Invasive Ductal Carcinoma.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {722992}, pmid = {34621293}, issn = {1664-8021}, abstract = {Background: Invasive ductal carcinoma (IDC) is the most common type of metastatic breast cancer. Due to the lack of valuable molecular biomarkers, the diagnosis and prognosis of IDC remain a challenge. A large number of studies have confirmed that coagulation is positively correlated with angiogenesis-related factors in metastatic breast cancer. Therefore, the purpose of this study was to construct a COAGULATION-related genes signature for IDC using the bioinformatics approaches. Methods: The 50 hallmark gene sets were obtained from the molecular signature database (MsigDB) to conduct Gene Set Variation Analysis (GSVA). Gene Set Enrichment Analysis (GSEA) was applied to analyze the enrichment of HALLMARK_COAGULATION. The COAGULATION-related genes were extracted from the gene set. Then, Limma Package was used to identify the differentially expressed COAGULATION-related genes (DECGs) between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) samples in GSE26340 data set. A total of 740 IDC samples from The Cancer Genome Atlas (TCGA) database were divided into a training set and a validation set (7:3). The univariate and multivariate Cox regression analyses were performed to construct a risk signature, which divided the IDC samples into the high- and low-risk groups. The overall survival (OS) curve and receiver operating characteristic (ROC) curve were drawn in both training set and validation set. Finally, a nomogram was constructed to predict the 1-, 2-, 3-, 4-, and 5-year survival rates of IDC patients. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic genes. Results: The "HALLMARK_COAGULATION" was significantly activated in IDC. There was a significant difference in the clinicopathological parameters between the DCIS and IDC patients. Twenty-four DECGs were identified, of which five genes (SERPINA1, CAPN2, HMGCS2, MMP7, and PLAT) were screened to construct the prognostic model. The high-risk group showed a significantly lower survival rate than the low-risk group both in the training set and validation set (p=3.5943e-06 and p=0.014243). The risk score was demonstrated to be an independent predictor of IDC prognosis. A nomogram including risk score, pathological_stage, and pathological_N provided a quantitative method to predict the survival probability of 1-, 2-, 3-, 4-, and 5-year in IDC patients. The results of decision curve analysis (DCA) further demonstrated that the nomogram had a high potential for clinical utility. Conclusion: This study established a COAGULATION-related gene signature and showed its prognostic value in IDC through a comprehensive bioinformatics analysis, which may provide a potential new prognostic mean for patients with IDC.}, } @article {pmid34619708, year = {2022}, author = {Russell, DH and Epstein, JI}, title = {Intraductal Adenocarcinoma of the Prostate With Cribriform or Papillary Ductal Morphology: Rare Biopsy Cases Lacking Associated Invasive High-grade Carcinoma.}, journal = {The American journal of surgical pathology}, volume = {46}, number = {2}, pages = {233-240}, doi = {10.1097/PAS.0000000000001819}, pmid = {34619708}, issn = {1532-0979}, mesh = {Adenocarcinoma, Papillary/classification/*pathology/therapy ; Biopsy ; Carcinoma, Ductal/classification/*pathology/therapy ; Humans ; Male ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; Prostatic Neoplasms/classification/*pathology/therapy ; Terminology as Topic ; Treatment Outcome ; }, abstract = {Prostatic duct adenocarcinoma, characterized by pseudostratified columnar epithelium, has historically been considered invasive carcinoma, although it may commonly have an intraductal component. Usual (acinar) intraductal carcinoma of the prostate (IDC-P) is a noninvasive high-risk lesion typically associated with high-grade, high-stage prostate cancer. Whereas there have been rare biopsy studies of pure acinar IDC-P or IDC-P associated with only low-grade carcinoma, there have been no analogous series of IDC-P with cribriform or papillary ductal morphology on biopsy unassociated with invasive high-grade carcinoma. We identified 14 patients with biopsies showing IDC-P with ductal morphology, defined as prostatic duct adenocarcinoma confined to glands/ducts with immunohistochemically proven retention of basal cells. Our series includes 12 patients with pure IDC-P and 2 patients with concurrent low-volume Grade Group 1 invasive cancer in unassociated cores. Three patients underwent radical prostatectomy: 2/3 had high-grade cancer in their resection specimen (Grade Group 3, Grade Group 5), including 1 with advanced stage and nodal metastases; 1/3 had Grade Group 1 organ-confined carcinoma and spatially distinct IDC-P with ductal morphology. Five men had only follow-up biopsies: 2/5 had cancer (Grade Group 2, Grade Group 4); 1/5 had IDC-P (on 2 repeat biopsies); and 2/5 had benign transurethral resection of the prostate. In all 5 cases with invasive cancer, the invasive portion was comprised purely of acinar morphology; no invasive ductal component was identified. Five patients did not have follow-up biopsies and were treated with radiation therapy±androgen deprivation. One patient had no follow-up information. In an analogous situation to acinar IDC-P, we propose that rarely there is a precursor form of ductal adenocarcinoma that can exist without concurrent invasive high-grade carcinoma and propose the term "IDC-P with ductal morphology," consistent with the terminology for acinar prostate adenocarcinoma. Until more evidence is accumulated, we recommend reporting and treating patients with IDC-P with ductal morphology in a manner analogous to those with acinar IDC-P. As with pure IDC-P with acinar morphology, we would also recommend not grading pure IDC-P with ductal morphology. Finally, we propose a new addition to the diagnostic criteria of IDC-P to include intraductal lesions with ductal morphology consisting of papillary fronds or cribriform lesions lined by cytologically atypical pseudostratified epithelium.}, } @article {pmid34618610, year = {2021}, author = {Alkhawari, HA and Asbeutah, AM and Almajran, AA and AlKandari, LA}, title = {Kuwait National Mammography Screening Program: outcomes of 5 years of screening in Kuwaiti women.}, journal = {Annals of Saudi medicine}, volume = {41}, number = {5}, pages = {257-267}, pmid = {34618610}, issn = {0975-4466}, mesh = {Adult ; *Breast Neoplasms/diagnostic imaging/epidemiology ; Early Detection of Cancer ; Female ; Humans ; Kuwait/epidemiology ; *Mammography ; Mass Screening ; Middle Aged ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy among women in Kuwait, representing 39.8% of all female cancer cases.

OBJECTIVES: Report the data of the Kuwait National Mammography Screening Program (KNMSP) for a 5-year period.

DESIGN: Prospective data collection.

SETTING: Population-based screening.

SUBJECTS AND METHODS: We included mammography screens done for Kuwaiti women (age 40 years and older) who attended the KNMSP from 2014 to 2019 to screen for breast cancer. A full-field digital mammography system was used to acquire the mammographic images in craniocaudal and mediolateral oblique projections. Independent double-blind reading of the mammograms was performed by two radiologists.

MAIN OUTCOME MEASURE: Early detection of breast cancer.

SAMPLE SIZE: 14 773 asymptomatic women met inclusion criteria (mean [SD] age, 51.8 (8.2).

RESULTS: Lesions were detected in 551 women (3.7%). These included 233 malignant lesions (233/551, 42.3%), 57 high-risk lesions (10.3%) and 261 benign lesions (47.4%). The participation rate was 7.8% of the target population of women 40-69 years of age. The majority of breast cancer cases were reported in the age group 45-49 years (23.2%). The KNMSP study recall rate for 5 consecutive years was in a range of 11.9-16.5% (mean, 14.3%). The detection rate of ductal/lobular carcinoma in situ and invasive breast cancer were 2.5 and 13.6 per 1000 screened women, respectively. Invasive ductal carcinoma was the most common type. Only 4314 women followed up within 12-15 months of the first mammography for a retention rate of 29.2%.

CONCLUSIONS: Screening mammography improves early detection of breast cancer in women older than 40 years but poor participation is a limitation. We are aiming to increase the participation rate to 70% of the population.

LIMITATIONS: Lack of participation by women.

CONFLICT OF INTEREST: None.}, } @article {pmid34610495, year = {2021}, author = {Rousseau, S and Katz, D and Shlomi-Polachek, I and Frenkel, TI}, title = {Prospective risk from prenatal anxiety to post traumatic stress following childbirth: The mediating effects of acute stress assessed during the postnatal hospital stay and preliminary evidence for moderating effects of doula care.}, journal = {Midwifery}, volume = {103}, number = {}, pages = {103143}, doi = {10.1016/j.midw.2021.103143}, pmid = {34610495}, issn = {1532-3099}, mesh = {Anxiety/etiology ; *Doulas ; Female ; Humans ; Length of Stay ; Parturition ; Postpartum Period ; Pregnancy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/etiology ; }, abstract = {OBJECTIVE: Growing literature has identified childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth. The current study is the first to prospectively examine a pathway of risk from mothers' prenatal trait-anxiety, to Acute-Stress-Immediately-Following-Childbirth, and later symptoms of Post-Traumatic-Stress-Following-Childbirth, in a low-risk community sample. Auxiliary analyses explored whether doula care during childbirth moderated risk.

METHOD: 149 pregnant women were randomly selected. Prenatal trait-anxiety was assessed toward the end of pregnancy, Acute-Stress-Immediately-Following-Childbirth at two-days post-partum, and symptoms of Post-Traumatic-Stress-Following-Childbirth at one-month post-partum.

RESULTS: Results indicated a significant indirect pathway from prenatal trait-anxiety to Post-Traumatic-Stress-Following-Childbirth, through Acute-Stress-Immediately-Following-Childbirth. Two groups were generated ad hoc for auxiliary analyses: participants who opted to receive doula care during childbirth (n=21; 14%) versus participants who received care as usual (n=128; 86%). Analyses provided preliminary support for doula care as a potential moderator of risk.

CONCLUSIONS: Results point toward prenatal trait-anxiety and Acute-Stress-Immediately-Following-Childbirth as significant risk factors for Post-Traumatic-Stress-Following-Childbirth. Findings inform preventive screening implicating the prenatal period as well as the postnatal hospital stay as important time windows for preventive screening. Finally, preliminary support for moderating effects of doula care suggest that preventive interventions administered during the perinatal period may effectively reduce anxiety-related risk for Post-Traumatic-Stress-Following-Childbirth.}, } @article {pmid34601849, year = {2021}, author = {Ediz, C and Kaya, N and Akan, S}, title = {Synchronous Breast Cancer and Renal Leiomyoma.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {31}, number = {10}, pages = {1234-1236}, doi = {10.29271/jcpsp.2021.10.1234}, pmid = {34601849}, issn = {1681-7168}, mesh = {*Breast Neoplasms/surgery ; Female ; Humans ; *Leiomyoma/diagnostic imaging/surgery ; Mastectomy ; Neoplasm Recurrence, Local ; Sentinel Lymph Node Biopsy ; }, abstract = {We present a case of a 49-year Turkish woman who had synchronous renal leiomyoma and breast cancer. The patient was evaluated for a suspicious breast mass; and renal mass was detected incidentally by contrast-enhanced computed tomography (CT). Diagnostic tru-cut biopsy was performed for both masses. Breast mass biopsy was reported as invasive ductal carcinoma (IDC) while renal biopsy was described as benign mesenchymal tumour. According to the biopsy results, the renal mass was followed for six months. For breast cancer, segmental mastectomy and concomitant sentinel lymph node biopsy was performed. Histologically, the tumour was reported as IDC and low-grade cribriform ductal carcinoma in situ (less than 1%). Six months later, renal mass was excised by laparoscopic approach. Histopathological examination was consistent with renal leiomyoma. For both tumours, no recurrence within one year was found on follow-up. Key Words: Renal leiomyoma, Breast cancer, Laparoscopy.}, } @article {pmid34601301, year = {2022}, author = {Rousseau, S and Polachek, IS and Frenkel, TI}, title = {A machine learning approach to identifying pregnant women's risk for persistent post-traumatic stress following childbirth.}, journal = {Journal of affective disorders}, volume = {296}, number = {}, pages = {136-149}, doi = {10.1016/j.jad.2021.09.014}, pmid = {34601301}, issn = {1573-2517}, mesh = {Delivery, Obstetric ; Female ; Humans ; Machine Learning ; Parturition ; Postpartum Period ; Pregnancy ; Pregnant Women ; *Stress Disorders, Post-Traumatic/diagnosis ; }, abstract = {INTRO: Recent literature identifies childbirth as a potentially traumatic event, following which mothers may develop symptoms of Post-Traumatic-Stress-Following-Childbirth (PTS-FC). Especially when persistent, PTS-FC may interfere with mothers' caregiving and associated infant development, underscoring the need for accurate predictive screening of risk. Drawing on recent developments in advanced statistical modeling, the aim of the current study was to identify a set of prenatal indicators and prediction rules that may accurately identify pregnant women's risk for developing symptoms of PTS-FC which persist throughout the early postpartum period.

METHODS: 182 women from the general population completed a comprehensive set of approximately 200 potentially predictive questions during pregnancy, and subsequently reported on their acute stress and PTS-FC at three days, one month, and three months postpartum (self-report and clinician-administered interview). Based on the postpartum acute stress and PTS-FC data, women were classified into profiles of "Stable-High-PTS-FC" and "Stable-Low-PTS-FC" by means of Latent-Class Analyses. Prenatal data were modeled to identify women at risk for "Stable-High PTS-FC".

RESULTS: Employing machine-learning decision-tree analyses, a total of 36 questions and 7 prediction-rules were selected. Based on a cost-rate of 15 versus 100 for false-negative "Stable-Low-PTS-FC" versus false-negative "Stable-High-PTS-FC", the final model showed 80.6% accuracy for "Stable-High-PTS-FC" prediction.

DISCUSSION: This study identifies a short set of questions and prediction rules that may be included in future large-scale validation studies aimed at developing and validating a brief PTS-FC screening instrument that could be implemented in general population prenatal healthcare practice. Accurate screening would allow for selective administering of preventive interventions towards women at risk.}, } @article {pmid34597463, year = {2021}, author = {Bishop, JA}, title = {IDK what's next for IDC: The unfolding saga of intraductal carcinoma of salivary glands.}, journal = {Cancer cytopathology}, volume = {129}, number = {12}, pages = {926-927}, doi = {10.1002/cncy.22508}, pmid = {34597463}, issn = {1934-6638}, mesh = {*Carcinoma, Ductal/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Humans ; Salivary Glands/pathology ; }, } @article {pmid34597458, year = {2021}, author = {Viswanathan, K and Sadow, PM and Maleki, Z and Nishino, M and Baloch, ZW and Abbott, TE and Rao, R and Faquin, WC}, title = {Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.}, journal = {Cancer cytopathology}, volume = {129}, number = {12}, pages = {928-946}, pmid = {34597458}, issn = {1934-6638}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; 1PO1CA240239-01//National Cancer Institute of the National Institutes of Health/ ; }, mesh = {Biopsy, Fine-Needle/methods ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Gene Fusion ; Humans ; *Salivary Gland Neoplasms/pathology ; Salivary Glands/pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.

METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.

RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.

CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.}, } @article {pmid34592934, year = {2021}, author = {Mathew, D and Gupta, S and Ashman, N}, title = {A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.}, journal = {BMC nephrology}, volume = {22}, number = {1}, pages = {324}, pmid = {34592934}, issn = {1471-2369}, mesh = {Adult ; Autoantibodies/*blood ; Breast Neoplasms/*complications ; Estrogen Receptor beta/analysis ; Female ; Glomerulonephritis, Membranous/*complications/immunology ; Humans ; Kidney/pathology ; Receptors, Phospholipase A2/*immunology ; }, abstract = {BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.

CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.

DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.}, } @article {pmid34592507, year = {2021}, author = {Pozza, A and Dèttore, D and Marazziti, D and Doron, G and Barcaccia, B and Pallini, S}, title = {Facets of adult attachment style in patients with obsessive-compulsive disorder.}, journal = {Journal of psychiatric research}, volume = {144}, number = {}, pages = {14-25}, doi = {10.1016/j.jpsychires.2021.09.045}, pmid = {34592507}, issn = {1879-1379}, mesh = {Adult ; Anxiety ; Anxiety Disorders/diagnosis ; *Hoarding ; Humans ; *Obsessive-Compulsive Disorder/diagnosis ; Surveys and Questionnaires ; }, abstract = {Literature data did not show univocal evidence in discriminating which form of attachment insecurity is involved in obsessive-compulsive disorder (OCD): both anxiety and avoidance was related to OCD symptomatology. No study used the Attachment Style Questionnaire (ASQ) that allows for investigation of differentiated facets of attachment anxiety and of avoidance. We investigated: (1) whether individuals with OCD differed from controls in the facets of attachment security (anxiety and avoidance), (2) which attachment facets predicted a diagnosis of OCD, controlling for socio-demographics and obsessive beliefs, (3) which attachment facets predicted specific OCD symptoms, controlling for socio-demographics and obsessive beliefs. Two hundred seventy participants (135 OCD patients and 135 matched controls) completed the Obsessive-Compulsive Inventory-Revised, Obsessive Beliefs Questionnaire-46 and ASQ. OCD patients reported respectively lower and higher levels on confidence and attachment anxiety than controls. Higher need of approval was the most important predictor of OCD diagnosis beyond the other attachment facets, and even of the obsessive beliefs. Using multivariate generalised linear models, the two facets of attachment anxiety, the need for approval (that predicted higher levels of obsessing and ordering symptoms), and preoccupation with relationships (that predicted higher hoarding symptoms) seemed to explain variance over and above OCD-related beliefs and socio-demographics. Discomfort with closeness contributed to the predictions of ordering symptoms. In conclusion, the interpersonal dynamics related to attachment in OCD patients should be carefully considered during assessment and treatment of OCD patients in clinical practice.}, } @article {pmid34587941, year = {2021}, author = {Teughels, W and Celik, GU and Tarce, M and De Cock, I and Persyn, SM and Haytac, MC}, title = {The effect of choline-stabilized orthosilicic acid in patients with peri-implantitis: an exploratory randomized, double-blind, placebo controlled study.}, journal = {BMC oral health}, volume = {21}, number = {1}, pages = {485}, pmid = {34587941}, issn = {1472-6831}, mesh = {Choline ; *Dental Implants/adverse effects ; Double-Blind Method ; Humans ; *Peri-Implantitis/diagnostic imaging/drug therapy ; Periodontal Index ; Treatment Outcome ; }, abstract = {BACKGROUND: Choline-stabilized orthosilicic acid (CS-OSA) was previously found to stimulate bone collagen formation in osteopenia and to improve biomarkers of cartilage degradation in knee osteoarthritis. The aim of the present study was to investigate the effect of oral administration of CS-OSA on clinical symptoms of peri-implantitis and the associated bone loss.

METHODS: Twenty-one patients with peri-implantitis were randomized in CS-OSA or placebo groups. After initial clinical and cone beam computed tomography (CBCT) measurements [probing pocket depth (PPD), bleeding on probing (BOP), mucosal recession (REC), distance from implant shoulder to alveolar crest (IS-AC) and distance from implant shoulder to first bone-to-implant contact (IS-BIC)], flap operations were performed at the peri-implantitis sites. All patients were instructed to use either placebo or CS-OSA capsules twice a day for 1 year. Measurements were repeated 6 and 12 months after randomization.

RESULTS: The data of 18 patients (36 implants) were used in the per protocol analysis. PPD and BOP improved significantly (p < 0.05) compared to baseline for both groups after 6 and 12 months. However, REC significantly increased in the placebo group but not in the CS-OSA group. The change in REC over 6 and 12 months was significantly different between groups (p < 0.01). IS-BIC and IS-AC measurements remained stable in the CS-OSA group whereas in the placebo group, both parameters increased significantly after 6 and 12 months. The change in IS-BIC over 12 months was significantly different between groups (p < 0.05).

CONCLUSION: The results of this preliminary study suggest that CS-OSA may stabilize and even prevent further bone loss after surgical peri-implantitis treatment and support mucosal tissue healing. Trial registration The trial was retrospectively registered at ISRCTN registry, registration number: ISRCTN14348802, registration date: 24/06/2020.}, } @article {pmid34587404, year = {2021}, author = {Yang, L and Xiong, Y and Sun, Z and Lin, X and Ni, H}, title = {Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {40}, number = {3}, pages = {51-61}, doi = {10.1615/JEnvironPatholToxicolOncol.2021038118}, pmid = {34587404}, issn = {2162-6537}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects/physiology ; Benzylisoquinolines/*pharmacology ; Body Weight/drug effects ; Carcinogens/toxicity ; Cell Proliferation/drug effects/physiology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Lipid Peroxidation/drug effects ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/metabolism/pathology ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/drug effects ; }, abstract = {AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals.

METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats.

RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats.

CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.}, } @article {pmid34576148, year = {2021}, author = {Heidenreich, E and Pfeffer, T and Kracke, T and Mechtel, N and Nawroth, P and Hoffmann, GF and Schmitt, CP and Hell, R and Poschet, G and Peters, V}, title = {A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles.}, journal = {International journal of molecular sciences}, volume = {22}, number = {18}, pages = {}, pmid = {34576148}, issn = {1422-0067}, support = {236360313//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Amino Acids/analysis ; Animals ; Body Fluids/metabolism ; Chromatography, High Pressure Liquid ; Dipeptides/*analysis/chemistry ; Mice, Inbred C57BL ; *Organ Specificity ; Reference Standards ; Reproducibility of Results ; Stereoisomerism ; *Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Amino acids have a central role in cell metabolism, and intracellular changes contribute to the pathogenesis of various diseases, while the role and specific organ distribution of dipeptides is largely unknown.

METHOD: We established a sensitive, rapid and reliable UPLC-MS/MS method for quantification of 36 dipeptides. Dipeptide patterns were analyzed in brown and white adipose tissues, brain, eye, heart, kidney, liver, lung, muscle, sciatic nerve, pancreas, spleen and thymus, serum and urine of C57BL/6N wildtype mice and related to the corresponding amino acid profiles.

RESULTS: A total of 30 out of the 36 investigated dipeptides were detected with organ-specific distribution patterns. Carnosine and anserine were most abundant in all organs, with the highest concentrations in muscles. In liver, Asp-Gln and Ala-Gln concentrations were high, in the spleen and thymus, Glu-Ser and Gly-Asp. In serum, dipeptide concentrations were several magnitudes lower than in organ tissues. In all organs, dipeptides with C-terminal proline (Gly-Pro and Leu-Pro) were present at higher concentrations than dipeptides with N-terminal proline (Pro-Gly and Pro-Leu). Organ-specific amino acid profiles were related to the dipeptide profile with several amino acid concentrations being related to the isomeric form of the dipeptides. Aspartate, histidine, proline and serine tissue concentrations correlated with dipeptide concentrations, when the amino acids were present at the C- but not at the N-terminus.

CONCLUSION: Our multi-dipeptide quantification approach demonstrates organ-specific dipeptide distribution. This method allows us to understand more about the dipeptide metabolism in disease or in healthy state.}, } @article {pmid34575694, year = {2021}, author = {Reichl, F and Muhr, D and Rebhan, K and Kramer, G and Shariat, SF and Singer, CF and Tan, YY}, title = {Cancer Spectrum, Family History of Cancer and Overall Survival in Men with Germline BRCA1 or BRCA2 Mutations.}, journal = {Journal of personalized medicine}, volume = {11}, number = {9}, pages = {}, pmid = {34575694}, issn = {2075-4426}, abstract = {BACKGROUND: Men with germline BRCA1/2 mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male BRCA1/2 mutation carriers.

METHODS: All men with germline BRCA1/2 mutations who attended genetic assessment between October 1995 and October 2019 at the Medical University of Vienna were identified. Clinicohistopathological features, family history of cancer, and outcomes were assessed by mutation status.

RESULTS: Of the 323 men included, 45 (13.9%) had a primary cancer diagnosis, many of whom were BRCA2 carriers (75.5%). Breast cancer (BC) was the most common cancer (57.8%) followed by prostate cancer (15.6%). Invasive ductal carcinoma and hormone receptor positive tumors were the most common. Among 26 BC-affected patients, 42% did not have any relatives with cancer. Parent of origin was only known in half of the 26 men, with 42% of them inherited through the maternal lineage versus 8% through the paternal. BRCA2 carriers and those with a family history of BC had worse overall survival (20 y vs. 23 y BRCA1 carriers; P = 0.007; 19 y vs. 21 y for those without family history of BC; P = 0.036).

CONCLUSION: Male BRCA2 carriers were most likely to develop cancer and had worse prognosis. In our dataset, BC was the most common cancer, likely due to referral bias. Not all mutation carriers present with BC or have a family history of cancer to warrant genetic testing.}, } @article {pmid34568216, year = {2021}, author = {Kalhan, S and Garg, S and Satarkar, R and Sharma, P and Hasija, S and Sharma, S}, title = {Correlation of Nuclear Morphometry with Clinicopathologic Parameters in Malignant Breast Aspirates.}, journal = {South Asian journal of cancer}, volume = {10}, number = {2}, pages = {64-68}, pmid = {34568216}, issn = {2278-330X}, abstract = {Objectives The primary objective of this study was to correlate nuclear morphometric parameters with clinicopathologic features such as cytologic grade, tumor size, lymph node status, mitotic index, and histopathologic grade. Secondary objective was to quantify nuclear changes on malignant breast aspirates using morphometry. Material and Methods Forty-five cases of carcinoma breast diagnosed on cytology were included in this study. These were graded into cytologic grades 1, 2, and 3 as per Robinson's cytologic grading system. Nuclear morphometry was done in all cases on smears stained with Papanicolaou stain. Clinicopathologic parameters including cytological grade, tumor size, lymph node status, mitotic count, and histological grade were correlated with nuclear morphometric parameters, namely, area, perimeter, shape, long axis, short axis, intensity, long-run emphasis, total run length, and T1 homogeneity. Results There were 9 cases in cytologic grade 1, 26 in grade 2, and 10 cases in cytologic grade 3. Histopathology showed 42 cases of infiltrating duct carcinoma, not otherwise specified (IDC, NOS) and 3 cases (6.7%) of ductal carcinoma in situ (DCIS). IDC (NOS) included 6, 27, and 9 cases in grades 1, 2, and 3, respectively. Majority of our cases had a tumor size less than 5 cm (n = 38, 84.4%) and had positive nodes (n = 30, 66.7%). Correlation of cytologic and histopathologic grades (including DCIS) with all morphometric features except long-run emphasis was statistically significant. Correlation of morphometry with tumor size yielded significant results for nuclear area, perimeter, long and short axes, and intensity with p < 0.05. Study of lymph node status (positive/negative) versus morphometry showed a highly significant statistical association with all the geometric as well as textural parameters. Mitotic count was significantly associated with all the geometric parameters and one textural parameter (total run length). Statistics Continuous variables were presented as mean ± standard deviation and compared using the two-tailed, independent sample t -test and one-way analysis of variance test. Tests were performed at significance level of 0.05. Conclusion Morphometry is an objective technique which holds immense promise in prognostication in breast carcinoma.}, } @article {pmid34568189, year = {2021}, author = {Saeed, U and Uppal, SR and Piracha, ZZ and Uppal, R}, title = {SARS-CoV-2 Spike Antibody Levels Trend among Sinopharm Vaccinated People.}, journal = {Iranian journal of public health}, volume = {50}, number = {7}, pages = {1486-1487}, pmid = {34568189}, issn = {2251-6093}, } @article {pmid34567263, year = {2021}, author = {Onitilo, AA and Engel, J and Joseph, AO and Li, YH}, title = {Is oestrogen receptor-negative/progesterone receptor-positive (ER-/PR+) a real pathological entity?.}, journal = {Ecancermedicalscience}, volume = {15}, number = {}, pages = {1278}, pmid = {34567263}, issn = {1754-6605}, abstract = {BACKGROUND: The existence of oestrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists.

METHODS: To re-evaluate breast cancers originally classified as ER-/PR+ via Oncotype DX® assay and compare molecular phenotype with Recurrence Score® (RS) result, clinicopathologic features and clinical outcomes were retrospectively obtained from electronic health records between January 1998 and June 2005. Archived formalin-fixed, paraffin-embedded (FFPE) tumour specimens were tested for the expression of ER, PR and human-epidermal-growth-factor-2. The number of positive ER-/PR+ samples confirmed by transcriptional analysis was the primary outcome of interest with event-free and overall survival as secondary outcomes. Biopsies from 26 patients underwent Oncotype DX testing and analysis.

RESULTS: Approximately 60% were middle-aged (40-50 years old) women, and 84.6% had invasive ductal carcinoma. Based on the Oncotype DX assay, approximately 65% (N = 17) had ER+/PR+ status; 23% (N = 6) had ER-/PR- status; and 12% had a single hormone positive receptor (1 ER-/PR+, 2 ER+/PR-) status. Almost one-quarter of patients were stratified into the low-RS (<18) or intermediate-RS (18-30) results, and half of the patients had a high-RS (>30) result.

CONCLUSION: Our findings suggest the ER-/PR+ subtype is not a reproducible entity and emphasises the value of retesting this subtype via molecular methods for appropriate treatment selection and patient outcomes. Multigene assay analysis may serve as a second-line or confirming tool for clinical determination of ER/PR phenotype in breast cancer patients for targeted therapies.}, } @article {pmid34566937, year = {2021}, author = {Pradhan, P and Margolin, W and Beuria, TK}, title = {Targeting the Achilles Heel of FtsZ: The Interdomain Cleft.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {732796}, pmid = {34566937}, issn = {1664-302X}, support = {R35 GM131705/GM/NIGMS NIH HHS/United States ; }, abstract = {Widespread antimicrobial resistance among bacterial pathogens is a serious threat to public health. Thus, identification of new targets and development of new antibacterial agents are urgently needed. Although cell division is a major driver of bacterial colonization and pathogenesis, its targeting with antibacterial compounds is still in its infancy. FtsZ, a bacterial cytoskeletal homolog of eukaryotic tubulin, plays a highly conserved and foundational role in cell division and has been the primary focus of research on small molecule cell division inhibitors. FtsZ contains two drug-binding pockets: the GTP binding site situated at the interface between polymeric subunits, and the inter-domain cleft (IDC), located between the N-terminal and C-terminal segments of the core globular domain of FtsZ. The majority of anti-FtsZ molecules bind to the IDC. Compounds that bind instead to the GTP binding site are much less useful as potential antimicrobial therapeutics because they are often cytotoxic to mammalian cells, due to the high sequence similarity between the GTP binding sites of FtsZ and tubulin. Fortunately, the IDC has much less sequence and structural similarity with tubulin, making it a better potential target for drugs that are less toxic to humans. Over the last decade, a large number of natural and synthetic IDC inhibitors have been identified. Here we outline the molecular structure of IDC in detail and discuss how it has become a crucial target for broad spectrum and species-specific antibacterial agents. We also outline the drugs that bind to the IDC and their modes of action.}, } @article {pmid34563762, year = {2021}, author = {Twick, M and Levy, DA}, title = {Fractionating the episodic buffer.}, journal = {Brain and cognition}, volume = {154}, number = {}, pages = {105800}, doi = {10.1016/j.bandc.2021.105800}, pmid = {34563762}, issn = {1090-2147}, mesh = {Amnesia ; Brain ; Hippocampus ; Humans ; *Memory, Episodic ; *Memory, Short-Term ; Neuropsychological Tests ; }, abstract = {The episodic buffer is a putative component of working memory proposed to account for several short-term memory functions, including unexpectedly preserved immediate prose recall by amnesic patients. Over the course of time, this component has increasingly become associated with binding functions. Considering recent findings regarding the performance of both memory-impaired and healthy individuals on the range of tasks purported to require the contribution of the episodic buffer, we suggest that it should be fractionated into two functional systems. One is a schematic store instantiated in brain areas responsible for conceptual and schema representations, which is likely to be hippocampus-independent, and preserved in the face of amnesia. In contrast, short-term maintenance of novel associative binding is likely to require the contribution of the hippocampus and may therefore not be functionally dissociable from long-term memory.}, } @article {pmid34561670, year = {2021}, author = {Kumar, V and Nawroth, PP}, title = {Is the association between diabetes mellitus and pulmonary fibrosis real?.}, journal = {Nature reviews. Endocrinology}, volume = {17}, number = {12}, pages = {703-704}, pmid = {34561670}, issn = {1759-5037}, mesh = {*Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Fibrosis/epidemiology ; Risk Factors ; }, } @article {pmid34560418, year = {2021}, author = {Wan, D and Zhang, Y and Yu, Q and Li, F and Zhuo, J}, title = {14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.}, journal = {Pathology, research and practice}, volume = {227}, number = {}, pages = {153619}, doi = {10.1016/j.prp.2021.153619}, pmid = {34560418}, issn = {1618-0631}, mesh = {14-3-3 Proteins/genetics/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/analysis ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/analysis ; Up-Regulation ; Young Adult ; Zinc Finger Protein Gli2/analysis ; }, abstract = {BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.

METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.

RESULTS: The positive expression rates of 14-3-3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3ζ was significantly increased in ADH, DCIS and IDC groups. 14-3-3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14-3-3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14-3-3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively.

CONCLUSION: 14-3-3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.}, } @article {pmid34557972, year = {2021}, author = {Han, J and Harrison, L and Patzelt, L and Wu, M and Junker, D and Herzig, S and Berriel Diaz, M and Karampinos, DC}, title = {Imaging modalities for diagnosis and monitoring of cancer cachexia.}, journal = {EJNMMI research}, volume = {11}, number = {1}, pages = {94}, pmid = {34557972}, issn = {2191-219X}, support = {SFB824/A9//deutsche forschungsgemeinschaft/ ; }, abstract = {Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities-that is, computed tomography, magnetic resonance imaging, ([18]F) fluoro-2-deoxy-D-glucose ([18]FDG) PET and dual-energy X-ray absorptiometry-shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.}, } @article {pmid34556536, year = {2021}, author = {Ruddock-Walker, S and Shaaban, S and Jacobson, JL and Meltzer, L and Minutti, CZ and Hovey, SW}, title = {Improving Timeliness of Insulin Administration by Using an Insulin Dose Calculator.}, journal = {Hospital pediatrics}, volume = {11}, number = {10}, pages = {1163-1173}, doi = {10.1542/hpeds.2020-003103}, pmid = {34556536}, issn = {2154-1671}, mesh = {Child ; Cohort Studies ; Electronic Health Records ; Humans ; *Inpatients ; *Insulin ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Insulin is a high-risk medication, and its dosing depends on the individualized clinical and nutritional needs of each patient. Our hospital implemented an insulin dose calculator (IDC) imbedded in the electronic medical record with the goal of decreasing average wait times in inpatient insulin ordering and administration. In this study, we evaluated whether implementation of an IDC decreased the average wait time for insulin administration for hospitalized pediatric patients.

METHODS: This pre- and postintervention cohort study measured wait times between point-of-care glucose testing and insulin administration. Patients admitted to the inpatient pediatric services who were treated with subcutaneous insulin during the study period were included. Additionally, nurses completed satisfaction surveys on the insulin administration process at our hospital pre- and post-IDC implementation. Descriptive statistics, χ[2], Fisher's exact test, and Student t tests were used to compare groups. Statistical process control charts were used to analyze data trends.

RESULTS: The preintervention cohort included 79 insulin doses for admitted pediatric patients. The postimplementation cohort included 128 insulin doses ordered via the IDC. Post-IDC implementation, the average wait time between point-of-care glucose testing and insulin administration decreased from 37 to 25 minutes (P < .05). The statistical process control chart revealed a 5-month run below the established mean after implementation of the IDC. Before IDC implementation, 15.6% of nurses expressed satisfaction in the insulin-dosing process compared with 69.2% postimplementation (P < .05).

CONCLUSIONS: Implementation of an IDC reduced the average wait time in ordering and administration of rapid-acting insulin and improved nursing satisfaction with the process.}, } @article {pmid34556291, year = {2021}, author = {Mangiardi-Veltin, M and Chamming's, F and Jaffre, A and Rousvoal, A and Tunon de Lara, C and Brouste, V and Hoppe, S and Sénéchal, C}, title = {[Prophylactic mastectomy and occult cancer: a ten-year experience at a cancer center].}, journal = {Bulletin du cancer}, volume = {108}, number = {11}, pages = {999-1009}, doi = {10.1016/j.bulcan.2021.05.007}, pmid = {34556291}, issn = {1769-6917}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/genetics ; Cancer Care Facilities ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Neoplasms, Unknown Primary/diagnostic imaging/*epidemiology/genetics ; Postoperative Complications/*epidemiology ; Prevalence ; Prophylactic Mastectomy/*adverse effects/methods ; Reoperation ; Retrospective Studies ; Time Factors ; }, abstract = {INTRODUCTION: Women identified as high-risk for breast cancer may choose between close follow-up and radical mastectomy. Prophylactic mastectomy, as any other surgery, is associated with benefits and harms. The aim of this study was to assess the morbidity associated with prophylactic mastectomy and to evaluate the prevalence of occult cancers.

METHODS: All patients who underwent unilateral or bilateral prophylactic mastectomy between 2007 and 2017 in our institution were eligible for inclusion in this retrospective study. Medical history, type of surgery, occurrence of complication or reoperation and pathological reports were examined in medical charts.

RESULTS: 79 women underwent prophylactic mastectomy over the studied period of which 58.2% were contralateral after breast cancer. A genetic mutation was present in 86.1% of cases. Postoperative complications occurred in 43.0% of cases. An additional surgery for medical or esthetic purpose was needed in 72.1% of cases. Occult cancer was found in 11.4% of the pathological reports. Triple negative invasive ductal carcinoma was discovered in two cases (2.5%).

DISCUSSION: Prophylactic mastectomy is the only effective preventive action against breast cancer. Women must be clearly informed of possible complications, high reoperation rate and potential pathological findings. Identifying women most at risk for breast cancer would help to better target those who will benefit most from surgery.}, } @article {pmid34555180, year = {2022}, author = {Giroud, M and Jodeleit, H and Prentice, KJ and Bartelt, A}, title = {Adipocyte function and the development of cardiometabolic disease.}, journal = {The Journal of physiology}, volume = {600}, number = {5}, pages = {1189-1208}, doi = {10.1113/JP281979}, pmid = {34555180}, issn = {1469-7793}, mesh = {Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/physiology ; Adipose Tissue, White/metabolism ; Animals ; *Cardiovascular Diseases/etiology/metabolism ; Diet, High-Fat/adverse effects ; Energy Metabolism ; Mice ; Obesity/metabolism ; Thermogenesis/physiology ; }, abstract = {Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which means temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease.}, } @article {pmid34550736, year = {2021}, author = {Greco, CM and Koronowski, KB and Smith, JG and Shi, J and Kunderfranco, P and Carriero, R and Chen, S and Samad, M and Welz, PS and Zinna, VM and Mortimer, T and Chun, SK and Shimaji, K and Sato, T and Petrus, P and Kumar, A and Vaca-Dempere, M and Deryagin, O and Van, C and Kuhn, JMM and Lutter, D and Seldin, MM and Masri, S and Li, W and Baldi, P and Dyar, KA and Muñoz-Cánoves, P and Benitah, SA and Sassone-Corsi, P}, title = {Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms.}, journal = {Science advances}, volume = {7}, number = {39}, pages = {eabi7828}, pmid = {34550736}, issn = {2375-2548}, support = {DP1 DK130640/DK/NIDDK NIH HHS/United States ; R00 HL138193/HL/NHLBI NIH HHS/United States ; T32 CA009054/CA/NCI NIH HHS/United States ; }, abstract = {The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE), in otherwise clock-less mice, and controlling timing of food intake. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal carbohydrate homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.}, } @article {pmid34548294, year = {2021}, author = {Fujimoto, A and Kosaka, Y and Hasebe, T and Saeki, T}, title = {Hidden breast cancer after breast augmentation, not presenting as a hypoechoic mass lesion, diagnosed using colour Doppler ultrasound.}, journal = {BMJ case reports}, volume = {14}, number = {9}, pages = {}, pmid = {34548294}, issn = {1757-790X}, mesh = {Aged, 80 and over ; Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging/surgery ; Female ; Fluorodeoxyglucose F18 ; Humans ; *Mammaplasty ; Ultrasonography, Doppler, Color ; }, abstract = {The main concern after breast augmentation with silicone injection is that silicone granulomas make it difficult to detect breast cancer. A case of breast cancer was diagnosed using colour Doppler ultrasound (CD) to detect an non-palpable mass not presenting as a hypoechoic mass lesion. An 83-year-old woman was incidentally found to have a lesion in her right breast, which was injected with silicone, showing 18F-fluorodeoxyglucose (FDG) uptake; the lesion was suspected to be breast cancer or silicone granuloma. A mass at the FDG uptake site was not detected on ultrasonography (US); however, observation using CD revealed a slightly hypoechoic area with hypervascularity. Core needle biopsy showed invasive ductal carcinoma. Patients in whom US does not reveal lesions after breast augmentation with silicone injection should undergo CD to detect hypervascularised tissue. To prevent false-negative biopsy results, CD is essential to detect cancer at suspected sites.}, } @article {pmid34547924, year = {2022}, author = {Moghalu, O and Stoffel, JT and Elliott, SP and Welk, B and Zhang, C and Presson, A and Myers, J}, title = {Time-Related Changes in Patient Reported Bladder Symptoms and Satisfaction after Spinal Cord Injury.}, journal = {The Journal of urology}, volume = {207}, number = {2}, pages = {392-399}, pmid = {34547924}, issn = {1527-3792}, support = {UL1 RR025764/RR/NCRR NIH HHS/United States ; UL1 TR000105/TR/NCATS NIH HHS/United States ; UL1 TR001067/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects/statistics & numerical data ; Cross-Sectional Studies ; Female ; Humans ; Intermittent Urethral Catheterization/*adverse effects/psychology/statistics & numerical data ; Male ; Patient Reported Outcome Measures ; Patient Satisfaction/*statistics & numerical data ; Prospective Studies ; Quality of Life ; Registries ; Self Report/statistics & numerical data ; Spinal Cord Injuries/*complications/therapy ; Time Factors ; Urinary Bladder/physiopathology ; Urinary Bladder, Neurogenic/etiology/psychology/*therapy ; Young Adult ; }, abstract = {PURPOSE: Increased time after spinal cord injury (SCI) is associated with a migration to bladder managements with higher morbidity such as indwelling catheter (IDC). Still, it is unclear how this affects bladder-related quality of life (QoL). We hypothesized that time from injury (TFI) would be associated with changes in bladder management, symptoms and satisfaction.

MATERIALS AND METHODS: Cross-sectional analysis of time-related changes in patient-reported bladder management, symptoms and satisfaction using the Neurogenic Bladder Research Group SCI Registry. Outcomes included Neurogenic Bladder Symptom Score (NBSS) and bladder-related satisfaction (NBSS-satisfaction). Multivariable regression was performed to assess associations between TFI and outcomes, adjusting for participant characteristics, injury specifics, and psychosocial aspects of health-related QoL. Participants with TFI <1 year were excluded and TFI was categorized 1-5 (reference), 6-10, 11-15, 16-20 and >20 years.

RESULTS: Of 1,420 participants mean age at injury was 29.7 years (SD 13.4) and mean TFI was 15.2 years (SD 11.6). Participants grouped by TFI included 298 (21%) 1-5, 340 (24%) 6-10, 198 (14%) 11-15, 149 (10%) 16-20 and 435 (31%) >20 years. As TFI increased, clean intermittent catheterization (CIC) declined (55% 1-5 vs 45% >20 years, p <0.001) and IDC increased (16% 1-5 vs 21% >20 years, p <0.001). On multivariable analysis, increased TFI was associated with fewer bladder symptoms at >20 years from injury (-3.21 [CI -1.29, -5.14, p <0.001]) and better satisfaction (6-10 years -0.20 [CI -0.41, 0.01, p=0.070], 11-15 years -0.36 [CI -0.60, -0.11, p=0.002], 16-20 years -0.59 [CI -0.86, -0.32, p <0.001], >20 years -0.85 [CI -1.07, -0.63, <0.001]).

CONCLUSIONS: After SCI, CIC decreases and IDC increases over time; however, increasing TFI is associated with reduced urinary symptoms and improved bladder-related satisfaction.}, } @article {pmid34543668, year = {2021}, author = {Chen, Z and Pham, H and Abreu, A and Amin, MB and Sherrod, AE and Xiao, GQ and Aron, M}, title = {Prognostic value of cribriform size, percentage, and intraductal carcinoma in Gleason score 7 prostate cancer with cribriform Gleason pattern 4.}, journal = {Human pathology}, volume = {118}, number = {}, pages = {18-29}, doi = {10.1016/j.humpath.2021.09.005}, pmid = {34543668}, issn = {1532-8392}, mesh = {Aged ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; }, abstract = {Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer; however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017-2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR)-free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity, and presence of IDC, whereas the presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22 of 111 (20%) patients after a median follow-up of 11 months, and of these, 21 had large cribriform pattern. On univariate analysis, all parameters had significant predictive values for BCR-free survival except for tertiary Gleason pattern 5. On multivariate analysis, while >20% cribriform pattern was trending to be an independent predictor, only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform, and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.}, } @article {pmid34540990, year = {2021}, author = {Wang, XD and Su, XJ and Chen, YK and Wang, WG}, title = {Regression of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: A case report.}, journal = {World journal of clinical cases}, volume = {9}, number = {24}, pages = {7285-7291}, pmid = {34540990}, issn = {2307-8960}, abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment.

CASE SUMMARY: Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment.

CONCLUSION: IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.}, } @article {pmid34540509, year = {2021}, author = {Das, S and Bramhachari, S and Halder, A and Tandon, A and Lalchandani, A}, title = {Synchronous Breast Carcinoma, Uterine Myoma, and Ovarian Teratoma in a Single Woman.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e17977}, pmid = {34540509}, issn = {2168-8184}, abstract = {Multiple primary tumors in a patient diagnosed with invasive ductal breast cancer are rarely reported in the literature. Here we present a case of invasive ductal carcinoma of the breast in a 42-year-old lady, with synchronous uterine leiomyoma (UL), ovarian teratoma and with prior history of follicular adenoma of thyroid in the same patient. The clinical presentation and management plan is discussed with a review of the literature. Breast cancer is the most common cancer in women where the concomitant occurrence of multiple primary tumors is a diagnostic and therapeutic challenge. In low- and middle-income countries, where facilities of genetic screening in all patients of synchronous neoplasia are limited due to scarcity of resources, strong clinical suspicion, multidisciplinary management, and follow-up remain important.}, } @article {pmid34538726, year = {2022}, author = {Ramotar, M and Chua, MLK and Truong, H and Hosni, A and Pintilie, M and Davicioni, E and Fleshner, NE and Dicker, AP and Bristow, RG and He, HH and van der Kwast, T and Den, RB and Berlin, A}, title = {Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.}, journal = {Urologic oncology}, volume = {40}, number = {1}, pages = {5.e1-5.e13}, doi = {10.1016/j.urolonc.2021.08.013}, pmid = {34538726}, issn = {1873-2496}, mesh = {Adult ; Aged ; Cohort Studies ; Combined Modality Therapy ; Genome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; *Prostatectomy ; Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery ; }, abstract = {PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.

MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.

RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)).

CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.}, } @article {pmid34535389, year = {2022}, author = {Lin, X and He, Y and Fu, S and Lin, S and Xue, E and Lin, L}, title = {The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.}, journal = {Clinical breast cancer}, volume = {22}, number = {3}, pages = {252-260}, doi = {10.1016/j.clbc.2021.08.004}, pmid = {34535389}, issn = {1938-0666}, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; *Calcinosis ; Capsules ; Diagnostic Errors/prevention & control ; Female ; Humans ; Male ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast.

MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3).

RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic.

CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.}, } @article {pmid34531293, year = {2021}, author = {Fritsche, A and Wagner, R and Heni, M and Kantartzis, K and Machann, J and Schick, F and Lehmann, R and Peter, A and Dannecker, C and Fritsche, L and Valenta, V and Schick, R and Nawroth, PP and Kopf, S and Pfeiffer, AFH and Kabisch, S and Dambeck, U and Stumvoll, M and Blüher, M and Birkenfeld, AL and Schwarz, P and Hauner, H and Clavel, J and Seißler, J and Lechner, A and Müssig, K and Weber, K and Laxy, M and Bornstein, S and Schürmann, A and Roden, M and de Angelis, MH and Stefan, N and Häring, HU}, title = {Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS).}, journal = {Diabetes}, volume = {70}, number = {12}, pages = {2785-2795}, doi = {10.2337/db21-0526}, pmid = {34531293}, issn = {1939-327X}, mesh = {Adolescent ; Adult ; Aged ; Behavior Therapy/methods ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/*prevention & control ; Female ; Germany ; Glucose Tolerance Test ; Humans ; *Life Style ; Male ; Middle Aged ; Patient Acuity ; Prediabetic State/blood/pathology/*therapy ; Risk Assessment ; Risk Reduction Behavior ; Treatment Outcome ; Young Adult ; }, abstract = {Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years' follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was -0.29 mmol/L [95% CI -0.54; -0.04], P = 0.025. Liver fat (-1.34 percentage points [95% CI -2.17; -0.50], P = 0.002) and cardiovascular risk (-1.82 percentage points [95% CI -3.13; -0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype-based LI may be beneficial for the prevention of diabetes.}, } @article {pmid34528573, year = {2021}, author = {Trontzas, IP and Syrigos, NK and Kotteas, EA}, title = {A case of trastuzumab-induced dermatomyositis.}, journal = {Journal of cancer research and therapeutics}, volume = {17}, number = {4}, pages = {1112-1114}, doi = {10.4103/jcrt.JCRT_209_19}, pmid = {34528573}, issn = {1998-4138}, mesh = {Antineoplastic Agents, Immunological/*adverse effects ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Dermatomyositis/chemically induced/*pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Trastuzumab/*adverse effects ; }, abstract = {Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention.}, } @article {pmid34527961, year = {2021}, author = {Loft, A and Herzig, S and Schmidt, SF}, title = {Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100805}, pmid = {34527961}, issn = {2666-1667}, mesh = {Animals ; Cell Nucleus/*chemistry/metabolism ; *Chromatin Immunoprecipitation Sequencing ; Cytological Techniques/*methods ; Female ; Green Fluorescent Proteins/*chemistry/genetics/metabolism ; Liver/chemistry/*cytology ; Male ; Mice ; *RNA-Seq ; }, abstract = {Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).}, } @article {pmid34527256, year = {2021}, author = {Fujimoto, A and Matsuura, K and Kawasaki, T and Ichinose, Y and Nukui, A and Hiratsuka, M and Asano, A and Shimada, H and Osaki, A and Saeki, T}, title = {Early HER2-positive breast cancer arising from a fibroadenoma: a case report.}, journal = {Oxford medical case reports}, volume = {2021}, number = {9}, pages = {omab083}, pmid = {34527256}, issn = {2053-8855}, abstract = {Breast cancer arising from fibroadenoma (FA) is rare, in which almost all reported cases are human epidermal growth factor receptor 2 (HER2)-negative. This is the first report to describe a case of HER2-positive breast cancer arising from FA that was treated with chemotherapy plus anti-HER2 therapy. In this early case, upfront surgery outcomes guided the selection of appropriate systemic therapy. A 31-year-old woman previously diagnosed with FA experienced tumor growth. Core needle biopsy and imaging studies confirmed a diagnosis of stage IIA HER2-positive invasive ductal carcinoma (IDC) with no evidence of lymph node metastasis (cT2N0M0). Breast-conserving surgery was performed. Pathological diagnosis revealed stage IA IDC with a predominant intraductal component (pT1aN0M0), arising from FA. In conclusion, we encountered an extremely rare case of HER2-positive breast cancer arising from FA in which pathological infiltration was difficult to predict based on preoperative imaging.}, } @article {pmid34522780, year = {2021}, author = {Chen, X and Chen, J and Liao, S and Cao, Y}, title = {Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review.}, journal = {Open life sciences}, volume = {16}, number = {1}, pages = {867-871}, pmid = {34522780}, issn = {2391-5412}, abstract = {Collision breast tumors, consisting of breast cancer (BC) and non-Hodgkin's lymphoma (NHL), are extremely rare. Here we report the case of a 64-year-old woman with a collision tumor in her left breast mass that was composed of invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia. In addition, we reviewed the published comparable English-language literature. Collision breast tumor composed of BC and NHL is extremely rare. For that reason, there is a lack of consensus about the underlying mechanism, and diagnosing it without delay remains a complex clinical challenge. We found that post-menopausal, age-related estrogen levels changes and Epstein-Barr virus infection are possible pathogenic factors. However, the symptoms are almost identical, and it is difficult to distinguish a simple breast tumor from a breast collision tumor. In this study, we reviewed the clinical features of all patients with BC and NHL colliding breast tumors; this information might enable early identification and prevention of misdiagnosis.}, } @article {pmid34520952, year = {2021}, author = {Wj, H and As, E and Js, R and C, P and Dh, B}, title = {Rates of margin positive resection with breast conservation for invasive breast cancer using the NCDB.}, journal = {Breast (Edinburgh, Scotland)}, volume = {60}, number = {}, pages = {86-89}, pmid = {34520952}, issn = {1532-3080}, mesh = {*Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Lobular/surgery ; Female ; Humans ; Margins of Excision ; Mastectomy ; Mastectomy, Segmental ; Retrospective Studies ; }, abstract = {BACKGROUND: Previous studies suggest the rate of positive surgical margin (PSM) after lumpectomy for breast cancer is approximately 20 %. The risk of PSM at time of resection is often a source of fear for patients, driving some to elect to undergo mastectomy. This study describes rates and predictors of positive margins for invasive breast cancers in the National Cancer Database (NCDB).

MATERIALS AND METHODS: From 2004 to 2013, patients with non-metastatic invasive breast cancers who underwent breast conservation surgery were identified from the NCDB. Patients' demographic, clinical, and facility of treatment characteristics were collected and compared. Per SSO-ASTRO-ASCO criteria, margin negative is defined as no gross or microscopic disease (i.e. no tumor on ink). Bivariate tests and multivariate logistic regression were conducted to identify independent predictors of patients with PSM at the time of resection.

RESULTS: A total of 707,798 patients were identified with non-metastatic invasive breast tumors who underwent lumpectomy. Rate of PSM across the entire cohort was 5.02 %. Over time, the rate of PSM decreased significantly from 6.54 % in 2004 to 3.91 % in 2013 (p < 0.001). Pure lobular histology predicted for the highest rate of PSM compared with IDC (8.63 vs 4.55 %; p < 0.001). In adjusted analysis, high grade, non-ductal histology and HER2 amplification were significantly associated with PSM with breast conservation while estrogen and progesterone status were not.

CONCLUSION: This study demonstrates a 5 % risk of PSM at time of breast conservation surgery using a large, modern national database. Patients with invasive lobular and mixed histology have a nearly two-fold risk of PSM compared to invasive ductal cancers. These results provide important data points to help appropriately counsel patients regarding the risk of PSM.}, } @article {pmid34516030, year = {2021}, author = {Mills, MN and Russo, NW and Fahey, M and Nanda, RH and Raiker, S and Jastrzebski, J and Stout, LL and Wilson, JP and Altoos, TA and Allen, KG and Blumencranz, PW and Diaz, R}, title = {Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.}, journal = {The oncologist}, volume = {26}, number = {11}, pages = {e1931-e1938}, pmid = {34516030}, issn = {1549-490X}, mesh = {Aged ; *Brachytherapy ; *Breast Neoplasms/radiotherapy ; *Carcinoma, Lobular/radiotherapy/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local/radiotherapy ; Retrospective Studies ; }, abstract = {BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences.

MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method.

RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p = .008) and lack of nodal evaluation (HR, 6.9; p = .01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p = .04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS.

CONCLUSION: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC.

IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%).}, } @article {pmid34515426, year = {2021}, author = {Brink, HM and Rubin, G and Benn, CA and Lucas, S}, title = {An audit of patients clinically deemed as high risk for malignant breast pathology at the Helen Joseph Hospital Breast Clinic.}, journal = {South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie}, volume = {59}, number = {3}, pages = {102-107}, pmid = {34515426}, issn = {2078-5151}, mesh = {Breast ; *Breast Neoplasms/diagnostic imaging ; Female ; Hospitals ; Humans ; *Mammography ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: The Helen Joseph Hospital Breast Clinic has implemented a clinical triage system for patients presenting with a variety of breast concerns. The goal of this system is to expedite the process from initial presentation to radiological assessment of patients with suspected breast malignancy or breast abscess in a resource limited setting. The objective was to assess the clinical, imaging and histological diagnoses of breast disease in these patients with malignancy and sepsis.

METHODS: A retrospective audit of patients clinically deemed high risk for malignant breast pathology referred to the breast imaging unit (BIU) in 2018. Patients were triaged based on strict clinical criteria: presence of a breast mass with or without lymph nodes or a breast abscess. Patients that were subsequently referred for mammography/ultrasound were identified using the patient files in the BIU. Results were recorded on Microsoft Excel and analysed using SAS version 9.2.

RESULTS: Three hundred and twenty-five patients were included in this study. Eighty-seven (26.8%) were diagnosed with breast cancer and 236 (72.6%) with benign disease. The most common presenting complaint was a palpable mass (n = 227; 69.9%). Ninety-five per cent of patients characterised as BI-RADS 5 had malignant disease. 55.8% of malignancies diagnosed on ultrasound had locally advanced disease. The most common histological diagnosis of malignancy was invasive ductal carcinoma (n = 67, 77%). The most commonly diagnosed benign disease was breast abscess (n = 42, 17.8%).

CONCLUSION: BI-RADS findings correspond to similar studies, however, a large number of benign breast disease was diagnosed. This may indicate heightened clinical awareness of breast cancer diagnosis and early detection. A significant percentage of malignancies presented as locally advanced. Except for a lower number of invasive lobular carcinoma, the histological spectrum of malignant disease is similar to comparative studies.}, } @article {pmid34513212, year = {2021}, author = {Vijayaraghavan, GR and Kona, M and Maheswaran, A and Kandil, DH and Toke, MK and Vedantham, S}, title = {Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast.}, journal = {Journal of clinical imaging science}, volume = {11}, number = {}, pages = {48}, pmid = {34513212}, issn = {2156-7514}, support = {R01 CA195512/CA/NCI NIH HHS/United States ; R01 CA199044/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVES: Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists' interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC).

MATERIAL AND METHODS: This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained.

RESULTS: The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042-1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337-3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393-0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238-0.523). These features achieved an AUC of 0.799 (CI: 0.752-0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206-6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159-5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933-0.986) and hypoechoic features (OR: 0.399; CI: 0.198- 0.801), and achieved an AUC of 0.787 (CI: 0.733-0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744-4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412-4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937-0.985) and hypoechoic features (OR: 0.571; CI: 0.335-0.975), and achieved an AUC of 0.739 (CI: 0.689-0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17- 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177-0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98-4.505) and circumscribed margins (OR: 4.225; CI: 0.919-19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614-0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249-5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161-0.513), and achieved an AUC of 0.739 (CI: 0.671- 0.806). No statistical association was observed between US imaging morphology and BRCA mutation.

CONCLUSION: In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.}, } @article {pmid34509278, year = {2021}, author = {Dias, R and Mendes, ÂB and Lages, N and Machado, H}, title = {Ultrasound-guided fascial plane blocks as unique anesthetic technique for total mastectomy in a covid-19 era: A case report.}, journal = {Revista espanola de anestesiologia y reanimacion}, volume = {68}, number = {7}, pages = {408-413}, pmid = {34509278}, issn = {2341-1929}, mesh = {*Anesthetics ; *Breast Neoplasms/surgery ; *COVID-19 ; Female ; Humans ; Mastectomy ; Mastectomy, Simple ; Middle Aged ; *Nerve Block ; SARS-CoV-2 ; Stroke Volume ; *Ultrasonography, Interventional ; Ventricular Function, Left ; }, abstract = {INTRODUCTION: Regional anesthesia techniques were recently introduced to provide analgesia for breast surgery. These techniques are rarely used as the primary anesthesia due to the complexity of breast innervation, with numerous structures that can potentially be disrupted during breast surgery.

CASE REPORT: A female patient in her sixties diagnosed with invasive ductal carcinoma on her left breast was scheduled for a simple mastectomy. After anesthetic evaluation, identification of high risk perioperative cardiovascular complications, it was proposed to perform the surgery only with regional anesthesia. A combination of pectoral nerve block (Pecs II), pecto-intercostal fascial block (PIFB) and supraclavicular nerve block ultrasound-guided were successfully performed.

CONCLUSION: This is the first case reporting a novel approach in a patient with severe cardiopulmonary disease who underwent breast surgery in a COVID-19 era.}, } @article {pmid34507268, year = {2021}, author = {Greenwood, HI and Price, ER and Lee, AY and Kelil, T and Jones, C and Le, M and Jaswa, EG}, title = {Outcomes of screening mammography performed prior to fertility treatment in women ages 40-49.}, journal = {Clinical imaging}, volume = {80}, number = {}, pages = {359-363}, doi = {10.1016/j.clinimag.2021.08.028}, pmid = {34507268}, issn = {1873-4499}, mesh = {Adult ; *Breast Neoplasms/diagnostic imaging/epidemiology ; Early Detection of Cancer ; Female ; Humans ; *Mammography ; Mass Screening ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: There are currently various conflicting recommendations for breast cancer screening with mammography in women between ages 40-49. There are no specific guidelines for breast cancer screening in women of this age group prior to assisted reproductive technology (ART) for the treatment of infertility. The purpose of our study was to evaluate outcomes of screening mammography, specifically ordered for the purpose of pre-fertility treatment clearance in women aged 40-49 years old.

MATERIALS AND METHODS: This was an IRB approved retrospective study of women aged 40-49 presenting for screening mammography prior to ART between January 2010 and October 2018. Clinical history, imaging, and pathology results were gathered from the electronic medical record. Descriptive statistics were performed.

RESULTS: Our study cohort consisted of 118 women with a mean age of 42 years (range 40-49). Sixteen of 118 (14%) women were recalled from screening for additional diagnostic work-up. Five of the 16 (31%) were recommended for biopsy (BI-RADS 4 or 5). One of 5 biopsies yielded a malignant result (PPV 20%). Overall cancer detection rate was 0.85% or 8.5 women per 1000 women screened. The single cancer in this cohort was an ER+ PR+ HER2- invasive ductal carcinoma.

CONCLUSION: Screening mammography in women 40-49 performed prior to initiation of ART may identify asymptomatic breast malignancy. In accordance with ACR and SBI guidelines to screen women of this age group, women of this age group should undergo screening mammography prior to ART.}, } @article {pmid34503243, year = {2021}, author = {Patzelt, L and Junker, D and Syväri, J and Burian, E and Wu, M and Prokopchuk, O and Nitsche, U and Makowski, MR and Braren, RF and Herzig, S and Diaz, MB and Karampinos, DC}, title = {MRI-Determined Psoas Muscle Fat Infiltration Correlates with Severity of Weight Loss during Cancer Cachexia.}, journal = {Cancers}, volume = {13}, number = {17}, pages = {}, pmid = {34503243}, issn = {2072-6694}, abstract = {PURPOSE: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time.

METHODS: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section.

RESULTS: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = -0.55, p < 0.01) and baseline psoas PDFF (r = -0.52, p = 0.02) with maximum BMI change during the course of the disease.

CONCLUSION: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.}, } @article {pmid34503181, year = {2021}, author = {Cheung, YC and Chen, K and Yu, CC and Ueng, SH and Li, CW and Chen, SC}, title = {Contrast-Enhanced Mammographic Features of In Situ and Invasive Ductal Carcinoma Manifesting Microcalcifications Only: Help to Predict Underestimation?.}, journal = {Cancers}, volume = {13}, number = {17}, pages = {}, pmid = {34503181}, issn = {2072-6694}, abstract = {BACKGROUND: The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict IDC underestimation.

METHODS: We reviewed patients who underwent mammography-guided biopsy on suspicious breast microcalcifications only and received contrast-enhanced spectral mammography (CESM) within 2 weeks before the biopsy. Those patients who were proven to have cancers (DCIS or IDC) by biopsy and subsequently had surgical treatment in our hospital were included for analysis. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were reviewed by consensus of two radiologists.

RESULTS: A total of 49 patients were included for analysis. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All nine unenhanced cancers were pure DCIS. Pure DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% vs. 27.8%) and solid enhancements (83.33% vs. 16.67%). The cancer and texture of enhancement were significantly different between pure DCIS and IDC, with moderate diagnostic performance for the former (p-value < 0.01, AUC = 0.66, sensitivity = 93%, specificity = 39%) and the latter (p-value < 0.01, AUC = 0.74, sensitivity = 65%, specificity = 83%). Otherwise, pure DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC (p = 0.0226 and 0.0018, respectively).

CONCLUSIONS: Nonmass and pure ground glass enhancements were closely related to pure DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC. Unenhanced DCIS with microcalcifications only has a low DCIS upgrade rate. The CESM-enhanced features could feasibly predict IDC underestimation.}, } @article {pmid34503159, year = {2021}, author = {Gawin, M and Kurczyk, A and Niemiec, J and Stanek-Widera, A and Grela-Wojewoda, A and Adamczyk, A and Biskup-Frużyńska, M and Polańska, J and Widłak, P}, title = {Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer.}, journal = {Cancers}, volume = {13}, number = {17}, pages = {}, pmid = {34503159}, issn = {2072-6694}, support = {2016/23/B/NZ4/03901//Narodowe Centrum Nauki/ ; }, abstract = {Intra-tumor heterogeneity (ITH) results from the coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed the potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After the on-tissue trypsin digestion of cellular proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated the relative homogeneity of cancer regions. However, when the number and diversity of the detected clusters of spectra were analyzed, differences between patient groups were observed. It is noteworthy that a higher degree of heterogeneity was found in tumors from patients who remained disease-free during a 5-year follow-up (n = 38) compared to tumors from patients with progressive disease (distant metastases detected during the follow-up, n = 21). Interestingly, such differences were not observed between patients with a different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in corresponding tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. Further, a positive correlation between the level of tumor-infiltrating lymphocytes and heterogeneity revealed by MSI was observed. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including infiltrating immune cells, that facilitated the response to treatment.}, } @article {pmid34499022, year = {2022}, author = {Mikulincer, M and Shaver, PR}, title = {Enhancing the "broaden-and-build" cycle of attachment security as a means of overcoming prejudice, discrimination, and racism.}, journal = {Attachment & human development}, volume = {24}, number = {3}, pages = {260-273}, doi = {10.1080/14616734.2021.1976921}, pmid = {34499022}, issn = {1469-2988}, mesh = {Attitude ; Humans ; Object Attachment ; *Racism ; }, abstract = {Attachment theory emphasizes both the importance of supportive relationship partners, beginning in infancy, for developing a sense of security, and the adaptive benefits of this sense. In this article, we consider bolstering the sense of attachment security as a means of reducing and overcoming prejudice, discrimination, and racism. We review basic concepts of attachment theory, focusing on what we call the broaden-and-build cycle of attachment security. We review studies showing that the sense of attachment security is associated with reduced prejudice and less discriminatory attitudes and behavior toward people outside one's own social or racial group. Finally, we propose theoretical ideas and research suggesting that attachment security can protect against the adverse psychological effects of others' acts of prejudice and discrimination toward oneself. We conclude that, despite large gaps in the research literature, attachment theory is a useful conceptual framework for understanding and combatting prejudice, discrimination, and racism.}, } @article {pmid34495428, year = {2021}, author = {Eguchi, Y and Yoshinaka, H and Hayashi, N and Sueyoshi, K and Uchikura, K and Nomoto, Y and Nagata, A and Saho, H and Shinden, Y and Ohtsuka, T}, title = {Accessory breast cancer in the inframammary region: a case report and review of the literature.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {203}, pmid = {34495428}, issn = {2198-7793}, abstract = {BACKGROUND: Although a few cases of accessory breast cancer (ABC) have been reported, most were in the axillary region. We encountered an extremely rare case of ABC in the inframammary region (IMR).

CASE PRESENTATION: The patient was a 68-year-old postmenopausal woman who had noticed a congenital accessory nipple in her left IMR with slight, occasional discharge 20 years ago. Recently, she noticed a mass under the accessory nipple and visited a nearby clinic; fine-needle aspiration cytology of the mass revealed that it was malignant. She presented to our department 2 weeks after she had noticed the mass. Physical and imaging examinations showed an irregular tumor mass 1.7 × 1.4 × 1.0 cm in size connected to the accessory nipple beneath the left normal breast. Neither distant metastasis nor lymph node swelling was observed. Ultrasound-guided core needle biopsy revealed the mass to be invasive ductal carcinoma. We diagnosed her tumor as ABC in the left IMR; cT1cN0M0: stage IA. Curative wide resection with sentinel node biopsy was performed. Intraoperative evaluation of the frozen section revealed a hot and green ipsilateral axillary lymph node that was free from carcinoma; therefore, nodal dissection was avoided. Histopathological examination including immunochemical staining revealed that the tumor was invasive ductal carcinoma arising from the accessory breast tissue, scirrhous type, 1.7 × 1.4 × 1.0 cm in size, with a solid intraductal component. There was no lymphovascular infiltration, and the surgical margin was 1.5 cm or more. The tumor was estrogen and progesterone receptor-positive, Her2/neu-negative, and had a Ki-67 labeling index of 20%. There was no involvement of the three hot and/or green nodes. The final classification was pT1cN0(sn)M0: stage IA. Letrozole 2.5 mg/day will be administered for 5 years as adjuvant hormonal therapy.

CONCLUSIONS: A cutaneous and/or subcutaneous lesion except for proper breast tissue on the milk line, or mammary ridge from axilla to groin may be an accessory breast tissue. Its serial abnormalities must be worried malignant potential to ductal carcinoma which needs some imaging and pathological examinations for definitive diagnosis and appropriate treatment according to the usual orthotopic breast cancer without delay.}, } @article {pmid34493237, year = {2021}, author = {Sazawal, S and Ryckman, KK and Das, S and Khanam, R and Nisar, I and Jasper, E and Dutta, A and Rahman, S and Mehmood, U and Bedell, B and Deb, S and Chowdhury, NH and Barkat, A and Mittal, H and Ahmed, S and Khalid, F and Raqib, R and Manu, A and Yoshida, S and Ilyas, M and Nizar, A and Ali, SM and Baqui, AH and Jehan, F and Dhingra, U and Bahl, R}, title = {Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.}, journal = {BMC pregnancy and childbirth}, volume = {21}, number = {1}, pages = {609}, pmid = {34493237}, issn = {1471-2393}, support = {001/WHO_/World Health Organization/International ; K12 HD043483/HD/NICHD NIH HHS/United States ; }, mesh = {Africa South of the Sahara/epidemiology ; *Algorithms ; Asia/epidemiology ; Cohort Studies ; Developing Countries ; Female ; *Gestational Age ; Humans ; Infant, Newborn ; *Machine Learning ; Male ; Metabolomics ; Neonatal Screening/*methods ; Pregnancy ; Premature Birth/*epidemiology ; Prospective Studies ; ROC Curve ; Ultrasonography, Prenatal ; }, abstract = {BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings.

METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed.

RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002).

CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.}, } @article {pmid34493033, year = {2021}, author = {Kar, H and Altındağ, SD and Etit, D and Yiğit, S and Acar, N and Tekindal, MA and Gür, Ö and Küçükzeybek, B and Akgül, Ö and Atahan, K}, title = {Clinicopathological features of mammary Paget’s disease: a single-center experience in Turkey.}, journal = {Turkish journal of medical sciences}, volume = {51}, number = {6}, pages = {2994-3000}, pmid = {34493033}, issn = {1303-6165}, mesh = {Adenocarcinoma ; Adult ; Aged ; Breast Neoplasms/epidemiology/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Paget's Disease, Mammary/epidemiology/mortality/*pathology ; Retrospective Studies ; Survival Analysis ; Turkey/epidemiology ; }, abstract = {BACKGROUND/AIM: Paget’s disease (PD) of the breast is a very rare presentation of breast malignancy, accounting for 1%–3% of all primary breast tumors. We aimed to evaluate and compare the clinicopathological features and clinical outcome of PD accompanied by in situ carcinoma and invasive cancer.

MATERIALS AND METHODS: We used the archive of our pathology laboratory retrospectively for age, sex, history of surgery, histopathological findings, treatment modalities, and follow-up information. We used the Kaplan–Meier method for survival analysis.

RESULTS: There were 46 female patients diagnosed with PD. In 39 (84.7%) patients, invasive carcinoma accompanied PD, while 7 (15.3%) patients had ductal carcinoma in situ. The median age at diagnosis was 53.5 years. The median follow-up period was 47 months. Of the 39 invasive carcinoma, 10 (25.6%) died during the follow-up period. Invasive ductal carcinoma group had a mean overall survival of rate of 57.8 ± 6.6 months. According to univariate analysis, only the tumor type was found to impact overall survival (p < 0.001).

CONCLUSIONS: The current study displayed the tumor type as the only parameter affecting overall survival in the invasive carcinoma group. Although it was not statistically significant, breast cancers accompanied by PD were found to be predominantly advanced stage tumors, high grade, hormone receptor negative, and HER2 positive.}, } @article {pmid34490749, year = {2021}, author = {Scheiber, D and Zweck, E and Albermann, S and Jelenik, T and Spieker, M and Bönner, F and Horn, P and Schultheiss, HP and Aleshcheva, G and Escher, F and Boeken, U and Akhyari, P and Roden, M and Kelm, M and Szendroedi, J and Westenfeld, R}, title = {Human myocardial mitochondrial oxidative capacity is impaired in mild acute heart transplant rejection.}, journal = {ESC heart failure}, volume = {8}, number = {6}, pages = {4674-4684}, pmid = {34490749}, issn = {2055-5822}, mesh = {*Diabetes Mellitus, Type 2 ; *Heart Diseases ; *Heart Transplantation/adverse effects ; Humans ; Mitochondria, Heart ; Oxidative Stress ; }, abstract = {AIMS: Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long-term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high-resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction.

METHODS AND RESULTS: We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high-resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P = 0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P = 0.57; chronic kidney disease stage 5: 8% vs. 9%, P > 0.99; arterial hypertension: 59% vs. 30%, P = 0.35), medications (tacrolimus: 100% vs. 91%, P = 0.54; mycophenolate mofetil: 92% vs. 91%, P > 0.99; prednisolone: 92% vs. 96%, P > 0.99) and time post-transplantation (21.5 ± 26.0 months vs. 29.4 ± 26.4 months, P = 0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8 ± 23.0 vs. 128.0 ± 33.0; P < 0.0001). Quantitative assessment of myocardial CD3[+] -lymphocyte infiltration identified ACR (1R) with a cut-off of >14 CD3[+] -lymphocytes/mm[2] (100% sensitivity, 82% specificity; P < 0.0001). Myocardial CD3[+] infiltration (r = -0.41, P < 0.05), systemic oxidative stress (thiobarbituric acid reactive substances; r = -0.42, P < 0.01) and myocardial oedema depicted by global CMR derived T2 time (r = -0.62, P < 0.01) correlated with lower oxidative capacity and overt cardiac dysfunction (global longitudinal strain; r = -0.63, P < 0.01).

CONCLUSIONS: Mild ACR with inflammatory cell infiltration associates with impaired mitochondrial bioenergetics in cardiomyocytes. Our findings may help to identify novel checkpoints in cardiac immune metabolism as potential therapeutic targets in post-transplant care.}, } @article {pmid34476342, year = {2021}, author = {Peila, R and Xue, X and Cauley, JA and Chlebowski, R and Manson, JE and Nassir, R and Saquib, N and Shadyab, AH and Zhang, Z and Wassertheil-Smoller, S and Rohan, TE}, title = {A Randomized Trial of Calcium Plus Vitamin D Supplementation and Risk of Ductal Carcinoma In Situ of the Breast.}, journal = {JNCI cancer spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {34476342}, issn = {2515-5091}, mesh = {Aged ; Breast Neoplasms/*epidemiology/prevention & control ; Calcium Carbonate/*administration & dosage ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/prevention & control ; Cholecalciferol/*administration & dosage ; Confidence Intervals ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Middle Aged ; Placebos/administration & dosage ; Postmenopause ; Proportional Hazards Models ; Risk ; Time Factors ; Vitamins/*administration & dosage ; }, abstract = {BACKGROUND: The effect of calcium plus vitamin D (CaD) supplementation on risk of ductal carcinoma in situ (DCIS) of the breast, a nonobligate precursor of invasive ductal carcinoma, is not well understood. In this secondary analysis, we examined this association in the Women's Health Initiative CaD trial over approximately 20 years of follow-up.

METHODS: A total of 36 282 cancer-free postmenopausal women (50-79 years) were randomly assigned to daily (d) calcium (1000 mg) plus vitamin D (400 IU) supplementation or to a placebo. Personal supplementation with vitamin D (≤600 IU/d, subsequently raised to 1000 IU/d) and calcium (≤1000 mg/d) was allowed. The intervention phase (median = 7.1 years), was followed by a postintervention phase (additional 13.8 years), which included 86.0% of the surviving women. A total of 595 incident DCIS cases were ascertained. Hazard ratios (HRs) plus 95% confidence intervals (CIs) were calculated.

RESULTS: The intervention group had a lower risk of DCIS throughout follow-up (HR = 0.82, 95% CI = 0.70 to 0.96) and during the postintervention phase (HR = 0.76, 95% CI = 0.61 to 0.94). The group that used CaD personal supplements in combination with the trial intervention had a lower risk of DCIS compared with the trial placebo group that did not use personal supplementation (HR = 0.72, 95% CI = 0.56 to 0.91).

CONCLUSIONS: CaD supplementation in postmenopausal women was associated with reduced risk of DCIS, raising the possibility that consistent use of these supplements might provide long-term benefits for the prevention of DCIS.}, } @article {pmid34475090, year = {2021}, author = {Watanabe, J and Nakamoto, S and Sugino, T}, title = {The Real-world Outcomes of Patients With Advanced Invasive Lobular Carcinoma of the Breast Compared With Invasive Ductal Carcinoma: A Review at a Single Institution.}, journal = {Anticancer research}, volume = {41}, number = {9}, pages = {4619-4627}, doi = {10.21873/anticanres.15275}, pmid = {34475090}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Carcinoma, Lobular/metabolism/mortality/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity.

PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER[+]), HER2-negative (HER2[-]) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively.

RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER[+] HER2[-] breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow.

CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER[+] HER2[-] breast cancer, ILC histopathology was associated with increased risk of death.}, } @article {pmid34472719, year = {2021}, author = {Guo, F and Yi, Z and Wang, W and Han, Y and Yu, P and Zhang, S and Ouyang, Q and Yan, M and Wang, X and Hu, X and Jiang, Z and Huang, T and Tong, Z and Wang, S and Yin, Y and Li, H and Yang, R and Yang, H and Teng, Y and Sun, T and Cai, L and Li, H and Chen, X and He, J and Liu, X and Yang, S and Fan, J and Qiao, Y and Wang, J and Xu, B}, title = {Profile, treatment patterns, and influencing factors of anthracycline use in breast cancer patients in China: A nation-wide multicenter study.}, journal = {Cancer medicine}, volume = {10}, number = {19}, pages = {6744-6761}, pmid = {34472719}, issn = {2045-7634}, support = {CH-BC-045//the Investigator-initiated program of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/ ; }, mesh = {Adult ; Aged ; Anthracyclines/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy ; China ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection.

METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889).

RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC.

CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.}, } @article {pmid34466203, year = {2021}, author = {Zingue, S and Atenguena, EO and Zingue, LL and Tueche, AB and Njamen, D and Nkoum, AB and Ndom, P}, title = {Epidemiological and clinical profile, and survival of patients followed for breast cancer between 2010 and 2015 at the Yaounde General Hospital, Cameroon.}, journal = {The Pan African medical journal}, volume = {39}, number = {}, pages = {182}, pmid = {34466203}, issn = {1937-8688}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Cameroon/epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/pathology ; Early Detection of Cancer/methods ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult ; }, abstract = {INTRODUCTION: approximately 6000 Cameroonian women died of cancer in 2018, and the breast is the most affected with 2625 new cases. The aim of this study was to establish a pattern of malignant breast tumours in Yaoundé (Cameroon).

METHODS: this study was a descriptive and analytical retrospective study of breast cancer between January 2010 and December 2015 in Yaoundé General Hospital (YGH) after the Institutional ethics committee approval. The variables studied were the socio-demographic characteristics, risk factors for breast cancer, types of tumours and type of treatments. The 5-year survival was analyzed by the Kaplan-Meier method. The adjusted hazard ratios and their 95% confidence intervals were calculated to assess the association between studied variables and patient survival through the cox regression using SPSS 23 software. The difference was considered significant at p < 0.05.

RESULTS: among the 344 files collected in this study, breast cancer patients were predominantly female (96.64%, n = 288) aged 45.39 ± 13.35 years, with invasive ductal carcinoma (68.03%, n = 270), located in the left breast (52%, n= 147). The average tumour size was ~6.5 ± 0.3 cm and diagnosed in grade II of Scarf Bloom Richardson (SBR) in 60% (n= 150) of cases. The 5-year survival was 43.3%. Factors associated with this poor survival were the religion (aHR 5.05, 95% CI: 1.57 - 16.25; p = 0.007 for animist and aHR 4.2, 95% CI: 1.53 - 11.46; p = 0.005 for protestant), location of the tumour (aHR 6.24, 95% CI: 1.58 - 24.60; p = 0.012), tumor height (aHR 0.21, 95% CI: 0.04 - 1.11; p = 0.011) and the time spent before medical treatment (aHR 5.12, 95% CI: 0.39 - 8.38; p = 0.011).

CONCLUSION: the young age, large tumour size and high histological grade in our studied population suggest a weak awareness of women about breast cancer. Action should be taken in early screening to improve the management of breast cancer in Cameroon.}, } @article {pmid34465119, year = {2021}, author = {Jesenková, A and Mergancová, J and Mergancová, J and Dvořáková, D and Šnáblová, E and Hácová, M}, title = {Phyllodes tumor and its malignization into invasive ductal carcinoma a case report.}, journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti}, volume = {100}, number = {6}, pages = {295-301}, doi = {10.33699/PIS.2021.100.6.295-301}, pmid = {34465119}, issn = {0035-9351}, mesh = {Breast ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal ; Female ; Humans ; Neoplasm Recurrence, Local ; *Phyllodes Tumor/diagnostic imaging/surgery ; }, abstract = {INTRODUCTION: Phyllodes tumors of the breast are rare and very distinct types of mammary neoplasms. They are characterized by their biphasicity, i.e. the presence of stromal and epithelial components at the same time. Malignancy is determined by the degree of stromal differentiation. The coexistence of the malignant epithelial component is a very rare phenomenon. Dozens of cases of simultaneous phyllodes tumor and epithelial malignancy have been reported so far. Nevertheless, the biological nature of this process is still an unexplained and a controversial topic.

CASE REPORT: In this paper, we present a case of a patient with a suddenly enlarging lesion in the breast. According to the first surgical resection, a diagnosis of high-grade malignant phyllodes tumor was made with fibrosarcoma differentiation, stromal overgrowth and suppression of the epithelial component. Examination of scar resistence in early postoperative period revealed a triple-negative invasive low-differentiated breast carcinoma with very high proliferative activity, thus malignization of the epithelial component of the tumor occurred. Shortly, a diagnosis of second recurrence was made, treatment included axillary lymph node dissection (ALND) with a negative histological findings. The patient underwent complex adjuvant chemotherapy and radiotherapy and remained disease free 3 years after the surgery.

CONCLUSION: Coexistence of phyllodes tumor and the breast carcinoma is very rare. The article describes the first published case, which documents the subsequent development of invasive low-differentiated ductal carcinoma immediately after resection of high-grade phyllodes tumor. Treatment and prognosis are generally determined by the characteristics of the carcinomatous component.}, } @article {pmid34461516, year = {2022}, author = {Meng, J and Yang, Q and Wan, W and Zhu, Q and Zeng, X}, title = {Physicochemical properties and adaptability of amine-producing Enterobacteriaceae isolated from traditional Chinese fermented fish (Suan yu).}, journal = {Food chemistry}, volume = {369}, number = {}, pages = {130885}, doi = {10.1016/j.foodchem.2021.130885}, pmid = {34461516}, issn = {1873-7072}, mesh = {Animals ; *Biogenic Amines ; China ; Enterobacter ; *Enterobacteriaceae/genetics ; Fermentation ; }, abstract = {The formation of biogenic amines (BAs) is an important potential danger in traditional fermented fish (Suan yu), and Enterobacteriaceae play an important role in the formation of BAs. The amine production abilities of 97 strains of Enterobacteriaceae screened from traditional fermented Suan yu were analyzed by reversed-phased high-performance liquid chromatography (HPLC). The genotypic diversity of amino acid decarboxylase on 23 strains of high-yield BAs was verified by PCR. Enterobacteriaceae with the highest production of amines was determined by analysis of the effects of physicochemical factors (pH, NaCl, temperature, and aerobic/anaerobic) on BA production and principal component analysis (PCA). The adaptability of the strains was examined using surimi simulation fermentation system, and the correlations among the indicators were analyzed using Cytoscape. Results showed that 97 strains of Enterobacteriaceae had strong amine-producing ability. Furthermore, 23 strains producing high yields of putrescine, cadaverine, and histamine were identified. All of the strains carried Idc, odc, speA, speB, and adiA, and five strains carried hdc. pH mainly affected the BA production of amine-producing bacteria. Three strains (Enterobacter asburiae 26C3, Klebsiella pneumoniae 47C2, and Morganella morganii 45C3) had the best amine-producing ability and used as the inoculated group. In this group, the values of BA (228.70-290.05 mg/kg) and the total volatile base nitrogen (TVB-N, 173.87-221.87 mg/100 g) exceeded the limit. Moreover, myofibrillar protein degradation was significant as indicated by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and decreased FAA content. Cytoscape software and principal component analysis (PCA) indicated that Enterobacteriaceae and pH were related to BA formation in Suan yu. These results provide a theoretical basis for controlling the BA of fermented fish products.}, } @article {pmid34455714, year = {2021}, author = {Ghalkhani, E and Akbari, MT and Izadi, P and Mahmoodzadeh, H and Kamali, F}, title = {Assessment of DAPK1 and CAVIN3 Gene Promoter Methylation in Breast Invasive Ductal Carcinoma and Metastasis.}, journal = {Cell journal}, volume = {23}, number = {4}, pages = {397-405}, pmid = {34455714}, issn = {2228-5806}, abstract = {OBJECTIVE: Metastasis might be latent or occur several years after primary tumor removal. Currently used methods for detection of distant metastasis have still some limitations. Blood tests may improve sensitivity and specificity of currently used screening procedures. The present study was designed to investigate promoter methylation status of DAPK1 and CAVIN3 genes in plasma circulating free DNA (cfDNA) samples in Iranian invasive ductal carcinoma (IDC) patients. We also investigated association of two gene promoter methylations with breast cancer (BC) and metastatic BC was also assessed.

MATERIALS AND METHODS: In this case-control study, MethySYBR assay was performed to determine DAPK1 and CAVIN3 promoter methylation status in breast IDC from 90 patients and 30 controls. Based on clinicopathological information, patient samples subdivided into stage I, II/III and IV groups (each group contained 30 individuals).

RESULTS: According to the results an increased promoter methylation level of the DAPK1 gene in BC patients was observed. It was found that as disease progressed, the percentage of methylation was changed while it was not significant. Methylation changes in metastatic and non-metastatic BC revealed that methylation levels were significantly increased in metastatic than non-metastatic group. Analysis revealed that promoter methylation of CAVIN3 gene in BC patients was significantly increased. The observed methylation changes from less to more invasive stages were not significant in the CAVIN3 gene. Moreover, promoter methylation was changed in metastatic rather than non-metastatic condition, although it was not significant.

CONCLUSION: Promoter hypermethylation of c and CAVIN3 genes in plasma are associated with the risk of BC and they can be potential diagnostic biomarkers along with current methods. Additionally, association of aberrant DAPK1 promoter methylation with metastasis suggests its potential usage as a non-invasive strategy for metastatic BC diagnosis.}, } @article {pmid34452576, year = {2021}, author = {Ameli, F and Ghafourina Nassab, F and Masir, N and Kahtib, F}, title = {Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {22}, number = {8}, pages = {2603-2609}, pmid = {34452576}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/enzymology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Matrix Metalloproteinase 13/*metabolism ; Middle Aged ; Neoplasms/enzymology/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.}, } @article {pmid34449311, year = {2021}, author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY}, title = {Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {142}, number = {}, pages = {111991}, doi = {10.1016/j.biopha.2021.111991}, pmid = {34449311}, issn = {1950-6007}, mesh = {Adult ; Aged ; Anesthesia, Conduction/*methods ; Anesthesia, General/*methods ; Anesthetics, Inhalation/administration & dosage ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Cohort Studies ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Nerve Block/methods ; Propofol/administration & dosage ; Radiotherapy, Adjuvant/methods ; Sevoflurane/administration & dosage ; Young Adult ; }, abstract = {PURPOSE: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

PATIENTS AND METHODS: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46-0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 2-3, and Her-2 positivity were 1.87 (1.03-3.42), 2.31 (1.20-4.44), 1.67 (1.09-2.56), 2.43 (1.18-4.97), 1.17 (1.03-1.19), 1.28 (1.13-2.24), 1.20 (1.05-2.22), and 1.59 (1.01-2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38-0.97) compared with that for no adjuvant radiotherapy.

CONCLUSION: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.}, } @article {pmid34448091, year = {2021}, author = {Jimbo, H and Horimoto, Y and Okazaki, M and Ishizuka, Y and Kido, H and Saito, M}, title = {Drug-induced aortitis of the subclavian artery caused by pegfilgrastim: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {197}, pmid = {34448091}, issn = {2198-7793}, abstract = {BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.

CASE PRESENTATION: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.

CONCLUSIONS: The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.}, } @article {pmid34442398, year = {2021}, author = {Mandapathil, M and Szczepanski, MJ and Jackson, EK and Lang, S and Whiteside, TL}, title = {Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells.}, journal = {Journal of personalized medicine}, volume = {11}, number = {8}, pages = {}, pmid = {34442398}, issn = {2075-4426}, support = {P30 DK079307/DK/NIDDK NIH HHS/United States ; U01 DE029759/DE/NIDCR NIH HHS/United States ; }, abstract = {INTRODUCTION: Adaptive regulatory T cells (Tr1) are induced in the periphery by environmental stimuli. CD73 expression and adenosine (ADO) production by tumor cells may influence Tr1 generation and their immunosuppressive activity.

MATERIAL AND METHODS: Tr1 were generated in co-cultures of CD4+CD25neg T cells, autologous immature dendritic cells (iDC), and irradiated ADO-producing CD73+ or non-producing CD73neg breast cancer (BrCa) cell lines (TU). The expression of ectonucleotidases and other surface markers on Tr1 was determined by flow cytometry. Tr1-mediated suppression of proliferation was evaluated in CFSE-based assays. Luciferase-based ATP detection assays and mass spectrometry were used to measure ATP hydrolysis and ADO levels. Cytokine levels were measured by ELISA or Luminex. CD73 expression on tumor cells or T cells in TU tissues was assessed by immunofluorescence.

RESULTS: CD73+ TU induced higher numbers of Tr1 cells (p < 0.01) than CD73neg TU. Tr1TU73+ hydrolyzed more exogenous ATP, produced more ADO, and mediated higher suppression than Tr1TU73neg (p < 0.05 for all). ARL67156, an ectonucleotidase inhibitor, and ZM241385, A2A receptor antagonist, reduced suppression of proliferation mediated by Tr1TU73+ cells (p < 0.01). Basal-like primary BrCa cells expressed higher levels of ectonucleotidases and induced more Tr1 than less aggressive primary luminal-like BrCa.

CONCLUSION: BrCa producing ADO (CD73+ TU) favor the induction of Tr1, which expresses CD39 and CD73, hydrolyzes ATP to ADO, and effectively suppresses anti-tumor immunity.}, } @article {pmid34439348, year = {2021}, author = {Kwong, A and Shin, VY and Ho, CYS and Khalid, A and Au, CH and Chan, KKL and Ngan, HYS and Chan, TL and Ma, ESK}, title = {Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, pmid = {34439348}, issn = {2072-6694}, support = {03143406//Health and Medical Research Fund/ ; }, abstract = {The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.}, } @article {pmid34437555, year = {2021}, author = {Shulman, D and Shnitzer-Akuka, M and Reifen-Tagar, M}, title = {The cost of attributing moral blame: Defensiveness and resistance to change when raising awareness to animal suffering in factory farming.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0254375}, pmid = {34437555}, issn = {1932-6203}, mesh = {Diet, Vegan/ethics ; Farms/*ethics ; Female ; Food Industry/*ethics ; Humans ; Male ; Meat ; *Morals ; *Motivation ; }, abstract = {Social change campaigns often entail raising awareness of harm caused by people's behavior. For example, campaigns to reduce meat eating frequently highlight the suffering endured by animals. Such messages may simultaneously attribute moral blame to individuals for causing the harm described. Given people's motivation to protect their moral self-image, we expected that information about the suffering of animals in the meat industry presented with a blaming (versus absolving) frame would generate greater defensiveness and correspondingly resistance to change in support of veg*nism (veganism/vegetarianism). We ran three studies to test this expectation. In two studies, we found that raising awareness of animal suffering using a blaming frame increased defensiveness, leading to lower veg*n-supporting attitudes and behavioral intentions. In one study, our hypothesis was not supported, however, a mini-meta analysis across the three studies suggests the overall pattern is robust. This work expands our understanding of the role of moral self-image preservation in defensiveness and resistance to change, and has applied relevance for the development of effective communication strategies in social and moral campaigns.}, } @article {pmid34436740, year = {2021}, author = {Elboga, U and Sahin, E and Kus, T and Cayirli, YB and Aktas, G and Uzun, E and Cinkir, HY and Teker, F and Sever, ON and Aytekin, A and Yilmaz, L and Aytekin, A and Cimen, U and Mumcu, V and Kilbas, B and Çelen, YZ}, title = {Superiority of [68]Ga-FAPI PET/CT scan in detecting additional lesions compared to [18]FDG PET/CT scan in breast cancer.}, journal = {Annals of nuclear medicine}, volume = {35}, number = {12}, pages = {1321-1331}, pmid = {34436740}, issn = {1864-6433}, mesh = {*Positron Emission Tomography Computed Tomography ; }, abstract = {PURPOSE: We compared the ability of [68]Ga-FAPI PET//CT with [18]FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options.

METHODS: A total of 48 patients with breast cancer underwent concurrent [68]Ga-FAPI-04 and [18]FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group.

RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in [68]Ga-FAPI PET/CT imaging with higher uptake values compared to [18]FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to [18]FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary [68]Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians.

CONCLUSION: It was determined that [68]Ga-FAPI PET/CT was superior to [18]FDG PET/CT in terms of accuracy and it was thought that [68]Ga-FAPI PET/CT could be utilized as an additional complementary imaging to [18]FDG PET/CT. Moreover, [68]Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.}, } @article {pmid34435696, year = {2021}, author = {Wang, Z and Zhu, S and Zhao, J and Nie, L and Chen, X and Zhang, M and Chen, N and Sun, G and Chen, J and Ni, Y and Dai, J and Liu, Z and Tao, R and Zhang, X and Zhu, X and Zhang, H and Liang, J and Wang, Z and He, B and Shen, P and Zeng, H}, title = {The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer.}, journal = {The Prostate}, volume = {81}, number = {15}, pages = {1191-1201}, pmid = {34435696}, issn = {1097-0045}, mesh = {Aged ; Androstenes/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Disease-Free Survival ; Docetaxel/*therapeutic use ; Humans ; Male ; Middle Aged ; Progression-Free Survival ; Prostate/pathology ; Prostatic Neoplasms/*drug therapy/mortality/pathology ; Prostatic Neoplasms, Castration-Resistant/*drug therapy/mortality/pathology ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment.

METHODS: We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns.

RESULTS: IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007).

CONCLUSION: Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.}, } @article {pmid34429412, year = {2021}, author = {Pauliuk, S and Heeren, N and Berrill, P and Fishman, T and Nistad, A and Tu, Q and Wolfram, P and Hertwich, EG}, title = {Global scenarios of resource and emission savings from material efficiency in residential buildings and cars.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {5097}, pmid = {34429412}, issn = {2041-1723}, abstract = {Material production accounts for a quarter of global greenhouse gas (GHG) emissions. Resource-efficiency and circular-economy strategies, both industry and demand-focused, promise emission reductions through reducing material use, but detailed assessments of their GHG reduction potential are lacking. We present a global-scale analysis of material efficiency for passenger vehicles and residential buildings. We estimate future changes in material flows and energy use due to increased yields, light design, material substitution, extended service life, and increased service efficiency, reuse, and recycling. Together, these strategies can reduce cumulative global GHG emissions until 2050 by 20-52 Gt CO2-eq (residential buildings) and 13-26 Gt CO2e-eq (passenger vehicles), depending on policy assumptions. Next to energy efficiency and low-carbon energy supply, material efficiency is the third pillar of deep decarbonization for these sectors. For residential buildings, wood construction and reduced floorspace show the highest potential. For passenger vehicles, it is ride sharing and car sharing.}, } @article {pmid34427055, year = {2021}, author = {Morigny, P and Kaltenecker, D and Zuber, J and Machado, J and Mehr, L and Tsokanos, FF and Kuzi, H and Hermann, CD and Voelkl, M and Monogarov, G and Springfeld, C and Laurent, V and Engelmann, B and Friess, H and Zörnig, I and Krüger, A and Krijgsveld, J and Prokopchuk, O and Fisker Schmidt, S and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {12}, number = {5}, pages = {1333-1351}, pmid = {34427055}, issn = {2190-6009}, support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; J4224-B34/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {1-Alkyl-2-acetylglycerophosphocholine Esterase ; Animals ; Benzaldehydes ; Biomarkers ; *Cachexia/drug therapy/etiology ; Humans ; Mice ; Oximes ; *Pancreatic Neoplasms ; Prospective Studies ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour-derived and host-derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.

METHODS: Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia-inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well-established mouse models of CCx and in different cohorts of weight-stable and weight-losing cancer patients with different tumour entities. Genetic PLA2G7 knock-down in tumours and pharmacological treatment using the well-studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour-bearing mice.

RESULTS: High expression and secretion of PLA2G7 were hallmarks of cachexia-inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock-down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.

CONCLUSIONS: Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre-cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.}, } @article {pmid34423517, year = {2021}, author = {Yun, NK and Slostad, JA and Naqib, A and Frankenberger, C and Perez, CB and Ghai, R and Usha, L}, title = {Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.}, journal = {The oncologist}, volume = {26}, number = {12}, pages = {1000-1005}, pmid = {34423517}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Precision Medicine ; Sequence Analysis, DNA ; }, abstract = {Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.}, } @article {pmid34417460, year = {2021}, author = {Gonzalez-Rellan, MJ and Fondevila, MF and Fernandez, U and Rodríguez, A and Varela-Rey, M and Veyrat-Durebex, C and Seoane, S and Bernardo, G and Lopitz-Otsoa, F and Fernández-Ramos, D and Bilbao, J and Iglesias, C and Novoa, E and Ameneiro, C and Senra, A and Beiroa, D and Cuñarro, J and Dp Chantada-Vazquez, M and Garcia-Vence, M and Bravo, SB and Da Silva Lima, N and Porteiro, B and Carneiro, C and Vidal, A and Tovar, S and Müller, TD and Ferno, J and Guallar, D and Fidalgo, M and Sabio, G and Herzig, S and Yang, WH and Cho, JW and Martinez-Chantar, ML and Perez-Fernandez, R and López, M and Dieguez, C and Mato, JM and Millet, O and Coppari, R and Woodhoo, A and Fruhbeck, G and Nogueiras, R}, title = {O-GlcNAcylated p53 in the liver modulates hepatic glucose production.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {5068}, pmid = {34417460}, issn = {2041-1723}, mesh = {Acetylglucosamine/*metabolism ; Animals ; Base Sequence ; Caloric Restriction ; Cell Line ; Colforsin/pharmacology ; Diabetes Mellitus, Type 2/complications/metabolism ; Epinephrine/metabolism ; Glucagon/metabolism ; Glucocorticoids/metabolism ; Gluconeogenesis/drug effects ; Glucose/*metabolism ; Glycosylation ; Hepatocytes/drug effects/metabolism ; Humans ; Hydrocortisone/metabolism ; Hyperglycemia/complications/metabolism ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/metabolism ; Liver/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications/metabolism ; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein Stability/drug effects ; Pyruvic Acid/metabolism ; RNA, Messenger/genetics/metabolism ; Transcription, Genetic/drug effects ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.}, } @article {pmid34413744, year = {2021}, author = {Moghimi, M and Khodadadi, K}, title = {Dermatomyositis following Biosimilar Trastuzumab in a Breast Cancer Patient: A Case Report.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {1134-1138}, pmid = {34413744}, issn = {1662-6575}, abstract = {Trastuzumab, as a recombinant IgG1 kappa, is a humanized monoclonal antibody against human epidermal growth factor receptor 2. Accordingly, it is widely used in breast cancers at early and advanced stages. Dermatomyositis is a rare adverse event of trastuzumab therapy, which is not well documented yet. In this study, a patient was treated for invasive ductal carcinoma with some symptoms of rash and generalized fatigue. These symptoms started after the fifth cycle of trastuzumab, which were gradually deteriorating. This patient's medical and family histories were unremarkable. The progression of the disease was ruled out as a possible cause of dermatomyositis, and the laboratory evaluation revealed a moderate increase in serum muscle protein (CPK). So, trastuzumab treatment was discontinued, and by passing 1 month from the start of prednisolone and hydroxychloroquine, the patient had no symptoms.}, } @article {pmid34413672, year = {2021}, author = {Kim, SJ and Lee, JH and Park, WJ and Kim, S}, title = {Bioinformatic Exploration for Prognostic Significance of Sphingolipid Metabolism-Related Genes in Invasive Ductal Carcinoma Using the Cancer Genome Atlas Cohort.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {4423-4434}, pmid = {34413672}, issn = {1178-7074}, abstract = {INTRODUCTION: Sphingolipid metabolism is a highly controlled process that is involved in regulating bioactive lipid signaling pathways and serves important roles in several cellular processes in breast cancer. Invasive ductal carcinoma (IDC), which is characterized by the malignant proliferation of the ductal epithelium and stromal invasion, is the most common type of breast cancer. Recent advances in genetic research have accelerated the discovery of novel prognostic factors and therapeutic targets for the disease. The aim of the present study was to investigate the expression and prognostic significance of sphingolipid metabolism-related genes in female IDC.

METHODS: The present study used gene expression RNAseq data obtained from The Cancer Genome Atlas breast invasive carcinoma (TCGA BRCA) datasets.

RESULTS: Sphingolipid metabolism-related genes exhibited dysregulated mRNA expression levels in IDC. The Student's t-test revealed that SMPDL3B, B4GALNT1, LPAR2, and LASS2 were significantly upregulated, while LASS3, LPAR1, B4GALT6, GAL3ST1, HPGD, ST8SIA1, UGT8, and S1PR1 were significantly downregulated in female IDC tissues compared with normal solid tissues. Kaplan-Meier survival analyses revealed that high SMPDL3B mRNA expression levels were associated with good prognosis in female IDC, suggesting that SMPDL3B plays a tumor suppressor role. To the best of our knowledge, the present study was the first to report that dysregulated expressions of SMPDL3B are significantly associated with age, estrogen receptor status, progesterone receptor status, and histological subtype.

CONCLUSION: Taken together, our study indicated that SMPDL3B may have a pathophysiological role and serve as a novel prognostic biomarker in IDC.}, } @article {pmid34410532, year = {2021}, author = {Omi, Y and Kamio, H and Yoshida, Y and Masui, K and Yamamoto, T and Nagashima, Y and Okamoto, T}, title = {Breast metastasis from medullary thyroid carcinoma: a report of a case.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {188}, pmid = {34410532}, issn = {2198-7793}, abstract = {BACKGROUND: Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.

CASE PRESENTATION: A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of [18]F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of [18]F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.

CONCLUSION: Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.}, } @article {pmid34409828, year = {2021}, author = {Shabanov, GA and Rybchenko, AA and Lugovaya, EA and Vdovenko, SI}, title = {[Biological age estimation based on the spectral analysis of the human brain bioelectric activity.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {34}, number = {3}, pages = {466-471}, pmid = {34409828}, issn = {1561-9125}, mesh = {*Aging ; *Brain ; Cell Differentiation ; Humans ; Risk Factors ; }, abstract = {For the first time, the research work offers a method of estimating human biological age based on the spectral analysis of the brain bioelectric activity. IDC decentralization index, which could consider summary degree of reduction of the background neurotrophic influences of the brain activating system on the peripheral tissues and organs, was developed. The close to linear dependence of the IDC index on the age of healthy people aged 10-90 as well as on the oncological patients' cancer G1-G4 cells differentiation was obtained. The cell disorders and mutations in relation with the age from 10 to 90 could be seen in growth of the IDC index from 100 to 900 units. The greater amount of the cell mutations in the oncological patients with the G1-G4 differentiation resulted in the IDC index growth up to the 3 000 units and more. All the obtained data allowed estimating the real biological age after a 10-minute registration of the human brain bioelectric activity. The accuracy increased with the averaging several surveys taken from one particular person. The technology will be highly efficient for scientific researches in the field of gerontology, monitoring of healthy people, revealing of risk groups, and for controlling of the cancer patients' medical treatment.}, } @article {pmid34408430, year = {2021}, author = {Rafiq, MT and A Hamid, MS and Hafiz, E}, title = {Effect of Progressive Resistance Strength Training on Body Mass Index, Quality of Life and Functional Capacity in Knee Osteoarthritis: A Randomized Controlled Trial.}, journal = {Journal of multidisciplinary healthcare}, volume = {14}, number = {}, pages = {2161-2168}, pmid = {34408430}, issn = {1178-2390}, abstract = {PURPOSE: This study aimed to investigate the effectiveness of progressive resistance strength training of the lower limb rehabilitation protocol (LLRP) on body mass index (BMI), quality of life, and functional capacity in patients with knee osteoarthritis (OA) who were overweight and obese.

PATIENTS AND METHODS: Fifty-six patients were allocated into either the Rehabilitation Protocol Group (RPG) or the Control Group (CG) by a computer-generated random number. The patients in the RPG performed the strengthening exercises of the LLRP and followed the instruction of daily care (IDC). The patients in the CG only followed the IDC as a usual care. Gait Speed Test, quality of life, and BMI were taken at pre-test and post-test measurements. Paired samples t-test and two way mixed analysis of variance were used to analyze the change of BMI within and compare the difference of BMI between the groups, respectively. Wilcoxon signed ranked test and Mann-Whitney U-test were used to analyze the changes of quality of life and functional capacity within and compare the differences of quality of life and functional capacity between the groups, respectively.

RESULTS: The patients in the RPG reported a significant reduction in BMI (p = 0.025), improvement in quality of life (p ≤ 0.001), and functional capacity (p ≤ 0.001) within group. The patients in the CG also reported a significant improvements in quality of life (p < 0.05). The improvement in quality of life score was greater in the patients with RPG than the CG (p = 0.053).

CONCLUSION: The progressive resistance strength training of LLRP is effective in terms of reducing BMI, improving quality of life and functional capacity.

TRIAL REGISTRATION: Name: Iranian Registry of Clinical Trials. Number: IRCT20191221045846N3. Enrollment of first participant: 27-07-2020.}, } @article {pmid34408355, year = {2021}, author = {Kohli, P and Penumadu, P and Srivastava, N and Srinivas, BH and Rangarajan, V}, title = {Primary Extra-Uterine Endometrial Stromal Sarcoma and Synchronous Breast Cancer: A Double Whammy: A Case report.}, journal = {Journal of obstetrics and gynaecology of India}, volume = {71}, number = {3}, pages = {326-329}, pmid = {34408355}, issn = {0971-9202}, abstract = {Endometrial stromal sarcoma is an uncommon gynecological tumor. Extra-uterine endometrial stromal sarcoma (EESS), the extra-uterine variant of its relatively more common counterpart, is even rarer with only few documented case reports. We report a case of a 40-year woman with bilateral adnexal tumors and synchronous invasive ductal breast carcinoma (IDC) posing a diagnostic challenge. The histopathology of specimen confirmed the diagnosis of EESS in the absence of florid endometriosis and synchronous hormone-positive infiltrating duct cancer in the breast. Patient was started on adjuvant endocrine therapy and is disease free at the end of 2 years. To the best of our knowledge, this is the first documentation of synchronous presentation of IDC and EESS, highlighting the possible role of hyper-estrogenemia as an etiological factor.}, } @article {pmid34401774, year = {2021}, author = {Madhavan, BK and Han, Z and Sickmann, A and Pepperkok, R and Nawroth, PP and Kumar, V}, title = {A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100700}, pmid = {34401774}, issn = {2666-1667}, mesh = {Biomechanical Phenomena/*physiology ; DNA/genetics ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Repair/genetics/*physiology ; Kinetics ; Lasers ; Microscopy, Confocal/*methods ; }, abstract = {With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).}, } @article {pmid34399237, year = {2021}, author = {Salih, AM and Hammood, ZD and Pshtiwan, LRA and Kakamad, FH and Salih, RQ and Ali, BS}, title = {Intermammary breast cancer; the first reported case.}, journal = {International journal of surgery case reports}, volume = {86}, number = {}, pages = {106223}, pmid = {34399237}, issn = {2210-2612}, abstract = {INTRODUCTION: Cancer of the breast is the most common cancer among females. The current study aims to report and discuss a rare case of breast cancer in the intermammary region.

CASE REPORT: A 61-year-old lady presented with intermammary swelling for three months. Ultrasound examination showed a hypoechoic micro lobulated mass with internal vascularity seated on the chest wall. There was pathological lymphnodes in the right axilla. Core needle biopsy suspected invasive ductal carcinoma of no specific type. The patient was referred to an oncology center receiving 21 cycles of radiotherapy and hormonal therapy.

DISCUSSION: The most common site of the occurrence of breast cancer is the upper outer quadrant (found in one-third of patients), followed by the upper inner quadrant (9.4%)-both lower outer and inner quadrants (5.2%) and rarely in the central portion. Intermammary breast cancer is an infrequent finding.

CONCLUSION: Although it is extremely rare, breast cancer could occur in the intermammary region. It has the same management strategy as breast cancer.}, } @article {pmid34397397, year = {2022}, author = {Cerimele, F and Tagliati, C and Salvatori, F and Baldassarre, S and Di Martino, A and Calamita, V and Pressanti, GL and Mingliang, Y and Giuseppetti, GM and Giovagnoni, A}, title = {Invasive ductal carcinoma mammographic findings: Correlation with age, breast composition and tumor size.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {45-49}, doi = {10.3233/BD-201072}, pmid = {34397397}, issn = {1558-1551}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging/*pathology ; Calcinosis/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/epidemiology ; Female ; Humans ; Logistic Models ; Mammography/*statistics & numerical data ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND/OBJECTIVE: The aim of this study was to identify the mammographic findings associated with malignancy in different age groups, taking into account breast composition (BC) and lesion size.

METHODS: Preoperative mammograms of 1023 invasive ductal carcinomas were retrospectively evaluated. According to the American College of Radiology Breast Imaging Reporting and Data System, cancer mammographic findings were classified as mass, calcifications, architectural distortion and asymmetry, and breasts were assessed as non-dense (A or B BC) and dense (C or D BC). Patient cohort was subdivided into three age groups (group 1: <50 years of age; group 2: between 50 and 69; group 3: ≥70 years of age).

RESULTS: Significant results of multinomial logistic regression were the association between mass and non-dense breast (p < 0.0001) and the association between mass and tumor size larger than 15 mm (p = 0.0049).

CONCLUSIONS: Mass finding of invasive ductal breast carcinoma is associated with breast composition and tumor size.}, } @article {pmid34396635, year = {2021}, author = {Dieng, O and Laurence, V and Logerot, C and Kirova, YM}, title = {Eribulin combined with radiation therapy in a young patient re-irradiated for a new lesion of breast cancer.}, journal = {The breast journal}, volume = {27}, number = {10}, pages = {787-790}, doi = {10.1111/tbj.14278}, pmid = {34396635}, issn = {1524-4741}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; *Breast Neoplasms/drug therapy/radiotherapy ; Female ; Furans/therapeutic use ; Humans ; Ketones ; Neoplasm Recurrence, Local ; }, abstract = {Eribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin.}, } @article {pmid34396426, year = {2021}, author = {Kobayashi, H and Nakai, T and Nakanishi, Y and Esumi, M and Masuda, S}, title = {Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.}, journal = {Molecular medicine reports}, volume = {24}, number = {4}, pages = {}, pmid = {34396426}, issn = {1791-3004}, mesh = {Adult ; Breast ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Carcinoma, Lobular/*classification/genetics/pathology ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; *Phylogeny ; Polymorphism, Single Nucleotide ; }, abstract = {Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal‑lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D‑loop, digital PCR targeting of chromosomes 1q and 16q, as well as next‑generation sequencing. DNA was extracted from formalin‑fixed paraffin‑embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non‑neoplastic mammary gland and extramammary organs, using laser‑assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele‑specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.}, } @article {pmid34393847, year = {2021}, author = {Goldstein Ferber, S and Shoval, G and Zalsman, G and Mikulincer, M and Weller, A}, title = {Between Action and Emotional Survival During the COVID-19 era: Sensorimotor Pathways as Control Systems of Transdiagnostic Anxiety-Related Intolerance to Uncertainty.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {680403}, pmid = {34393847}, issn = {1664-0640}, abstract = {Objectives: The COVID-19 pandemic and aligned social and physical distancing regulations increase the sense of uncertainty, intensifying the risk for psychopathology globally. Anxiety disorders are associated with intolerance to uncertainty. In this review we describe brain circuits and sensorimotor pathways involved in human reactions to uncertainty. We present the healthy mode of coping with uncertainty and discuss deviations from this mode. Methods: Literature search of PubMed and Google Scholar. Results: As manifestation of anxiety disorders includes peripheral reactions and negative cognitions, we suggest an integrative model of threat cognitions modulated by sensorimotor regions: "The Sensorimotor-Cognitive-Integration-Circuit." The model emphasizes autonomic nervous system coupling with the cortex, addressing peripheral anxious reactions to uncertainty, pathways connecting cortical regions and cost-reward evaluation circuits to sensorimotor regions, filtered by the amygdala and basal ganglia. Of special interest are the ascending and descending tracts for sensory-motor crosstalk in healthy and pathological conditions. We include arguments regarding uncertainty in anxiety reactions to the pandemic and derive from our model treatment suggestions which are supported by scientific evidence. Our model is based on systematic control theories and emphasizes the role of goal conflict regulation in health and pathology. We also address anxiety reactions as a spectrum ranging from healthy to pathological coping with uncertainty, and present this spectrum as a transdiagnostic entity in accordance with recent claims and models. Conclusions: The human need for controllability and predictability suggests that anxiety disorders reactive to the pandemic's uncertainties reflect pathological disorganization of top-down bottom-up signaling and neural noise resulting from non-pathological human needs for coherence in life.}, } @article {pmid34392891, year = {2021}, author = {Roberts, WC and Jeong, M}, title = {Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {157}, number = {}, pages = {101-106}, doi = {10.1016/j.amjcard.2021.07.023}, pmid = {34392891}, issn = {1879-1913}, mesh = {Adult ; Aged ; Cardiomyopathies/complications/epidemiology ; Cardiomyopathy, Dilated/*complications/epidemiology ; Female ; Follow-Up Studies ; *Forecasting ; Heart Failure/epidemiology/etiology/surgery ; Heart Transplantation ; Humans ; Incidence ; Middle Aged ; Peripartum Period ; Pregnancy ; *Pregnancy Complications, Cardiovascular ; Retrospective Studies ; Texas/epidemiology ; Young Adult ; }, abstract = {Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.}, } @article {pmid34392462, year = {2021}, author = {Fine, RE and Gilmore, RC and Dietz, JR and Boolbol, SK and Berry, MP and Han, LK and Kenler, AS and Sabel, M and Tomkovich, KR and VanderWalde, NA and Chen, M and Columbus, KS and Curcio, LD and Feldman, SM and Gold, L and Hernandez, L and Manahan, ER and Seedman, SA and Vaidya, RP and Sevrukov, AB and Aoun, HD and Hicks, RD and Simmons, RM}, title = {Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.}, journal = {Annals of surgical oncology}, volume = {28}, number = {10}, pages = {5525-5534}, pmid = {34392462}, issn = {1534-4681}, support = {https://clinicaltrials.gov/ct2/show/NCT02200705//IceCure Medical Ltd./ ; }, mesh = {Aged ; *Breast Neoplasms/surgery ; *Cryosurgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Prospective Studies ; }, abstract = {BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks.

METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method.

RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation.

CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.}, } @article {pmid34388695, year = {2021}, author = {Chamalidou, C and Fohlin, H and Albertsson, P and Arnesson, LG and Einbeigi, Z and Holmberg, E and Nordenskjöld, A and Nordenskjöld, B and Karlsson, P and Linderholm, B and , }, title = {Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up.}, journal = {Breast (Edinburgh, Scotland)}, volume = {59}, number = {}, pages = {294-300}, pmid = {34388695}, issn = {1532-3080}, mesh = {Aged ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular ; Female ; Follow-Up Studies ; Humans ; Prognosis ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial.

PURPOSE: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort.

MATERIAL AND METHODS: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed.

RESULTS: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC.

CONCLUSIONS: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.}, } @article {pmid34379693, year = {2021}, author = {He, X and Anthony, DC and Catoni, Z and Cao, W}, title = {Pulmonary tumor embolism: A retrospective study over a 30-year period.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0255917}, pmid = {34379693}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Autopsy ; Breast Neoplasms/complications/diagnosis/pathology ; Carcinoma, Ductal/complications/diagnosis/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/complications/diagnosis/*pathology ; Pulmonary Embolism/complications/*diagnosis ; Retrospective Studies ; Urinary Bladder Neoplasms/complications/diagnosis/pathology ; }, abstract = {BACKGROUND: Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

METHODS: We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.

RESULTS: We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3-17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).

CONCLUSIONS: The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.}, } @article {pmid34377307, year = {2021}, author = {Gan, J and Zhang, Z}, title = {Relationship between ultrasound values and pathology and metastasis in patients with breast cancer.}, journal = {American journal of translational research}, volume = {13}, number = {7}, pages = {8207-8213}, pmid = {34377307}, issn = {1943-8141}, abstract = {PURPOSE: This study was designed to investigate the relationship between ultrasound values of breast cancer and its pathology and metastasis.

METHODS: A retrospective study was conducted on 80 patients diagnosed with breast cancer by pathologic examination in our hospital. The tumor size, tumor type, tumor grade, and the presence of distant metastasis were recorded. Vascular invasion, molecular subtype, pathobiologic indicators, and other measures were analyzed to explore the correlation between ultrasound measurements and pathology and metastasis in breast cancer patients.

RESULT: The proportion of ultrasound scores did not differ significantly among the groups (P > 0.05). The enrolled subjects were grouped according to tumor types (intraductal carcinoma, invasive ductal carcinoma, invasive lobular carcinoma, and special types), tumor grade (grade 1-3), metastasis, vascular invasion, and pathobiologic indicators (positive or negative ER/PR and HER-2 expression). These factors affected the ultrasound scores of breast cancer patients, resulting in significant differences in the proportions of scores between the groups (P < 0.05).

CONCLUSION: The ultrasound scores of breast cancer are closely related to its pathologic changes, and this has implications for the types of pathological tissues, biologic indicators, and presence of metastasis. Therefore, ultrasound values may be useful as a primary pathologic screening method for breast cancer patients.}, } @article {pmid34377272, year = {2021}, author = {Eren Karanis, Mİ and Küçükosmanoğlu, İ and Ünlü, Y and Eryılmaz, MA and Köksal, H}, title = {Increased expression of ASRGL1 in invasive ductal carcinoma and its association with estrogen-progesterone receptor status of tumors.}, journal = {American journal of translational research}, volume = {13}, number = {7}, pages = {7928-7934}, pmid = {34377272}, issn = {1943-8141}, abstract = {AIMS: Human asparaginase-like protein 1 (ASRGL1) is closely related to tumor growth. ASRGL1 can significantly promote cell proliferation and suppress apoptosis. To date, high levels of expression of ASRGL1 have been reported in various tumors, but the function of ASRGL1 in carcinogenesis is still not well understood. In this study, we aimed to immunohistochemically investigate the expression of ASRGL1 in non-neoplastic breast tissue and invasive ductal carcinoma.

METHODS AND RESULTS: ASRGL1 was evaluated immunohistochemically in 148 invasive ductal carcinomas and 105 nonneoplastic breast tissue samples to assess the impact on breast cancer development and its association with clinicopathologic features. ASRGL1 was observed positive in 63 (42.6%) and negative in 85 (57.4%) invasive ductal carcinoma. In nonneoplastic breast tissue, 24 (22.9%) cases were ASRGL1 positive and 81 (77.1%) were negative. A significant difference was observed between invasive ductal carcinoma and nonneoplastic breast tissue in terms of ASRGL1 expression, and ASRGL1 expression was increased in invasive ductal carcinoma (P = .001). Most estrogen receptor-negative tumors and progesterone receptor-negative tumors were also negative with ASRGL1 and the difference was significant (P = .006 and P = .001, respectively). The correlation between the ASRGL1 expression of the tumors and event-free survival or overall survival was not significant (P>.05).

CONCLUSIONS: ASRGL1 may play a role in increasing cell proliferation and breast cancer development. ASRGL-1 expression in breast cancer closely correlates with the hormone receptor status of the tumor. In breast cancer, ASRGL-1 expression does not contribute to predicting tumor behavior.}, } @article {pmid34366444, year = {2021}, author = {Dey, A and Dhumal, CV and Sengupta, P and Kumar, A and Pramanik, NK and Alam, T}, title = {Challenges and possible solutions to mitigate the problems of single-use plastics used for packaging food items: a review.}, journal = {Journal of food science and technology}, volume = {58}, number = {9}, pages = {3251-3269}, pmid = {34366444}, issn = {0022-1155}, abstract = {Single-use plastic (SUP) being a versatile material, is adopted as an alternate to traditional materials specifically for the use in food packaging due to its inherent characteristics like high durability, inertness, and protecting ability but has become a curse for living being today due to its random usage and unplanned rejection to nature. Mostly plastics used in packaging of beverages, fresh meats, fruits and vegetables are under concern today. Single-use packages result in generation of several billion tons of garbage till date, which pollutes the environment. At the immediate past, it has come to light that micro plastics obtained due to slow degradation of SUP present in oceans, are also being consumed by marine organisms such as fishes and shellfish species which disturbs the marine life extensively. Hence, finding right strategy to mitigate the plastic waste related issues has becoming inevitable today. This review paper briefs various strategies undertaken worldwide to mitigate the pollution due to generation of plastic waste. Various notable impact of adopted strategies and recent innovations to replace the SUP products are also discussed and in view of this a roadmap is also suggested which can be used to achieve the milestone of Zero Plastic Waste.}, } @article {pmid34362902, year = {2021}, author = {Mani, L and Tzachor, A and Cole, P}, title = {Global catastrophic risk from lower magnitude volcanic eruptions.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4756}, pmid = {34362902}, issn = {2041-1723}, abstract = {Globalisation supports the clustering of critical infrastructure systems, sometimes in proximity to lower-magnitude (VEI 3–6) volcanic centres. In this emerging risk landscape, moderate volcanic eruptions might have cascading, catastrophic effects. Risk assessments ought to be considered in this light.}, } @article {pmid34360722, year = {2021}, author = {Tokarz, J and Möller, G and Artati, A and Huber, S and Zeigerer, A and Blaauw, B and Adamski, J and Dyar, KA}, title = {Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, pmid = {34360722}, issn = {1422-0067}, support = {ExNet-0041-Phase2-3 ("SyNergy-HMGU")//Helmholtz Association/ ; }, mesh = {Aging/*metabolism/pathology ; Animals ; Arginine/*metabolism ; Lysine/*metabolism ; Male ; Mice ; Muscle, Skeletal/*metabolism/pathology ; *Oxidative Stress ; *Signal Transduction ; }, abstract = {Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a 'rewired' metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.}, } @article {pmid34359556, year = {2021}, author = {Zhang, JQ and Cheng, TM and Lin, WC and Chiu, KC and Wu, SY}, title = {Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.}, journal = {Cancers}, volume = {13}, number = {15}, pages = {}, pmid = {34359556}, issn = {2072-6694}, abstract = {PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments.

METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group).

RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE.

CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.}, } @article {pmid34354885, year = {2021}, author = {Hashmi, AA and Riaz, R and Zia, S and Shahid, H and Malik, UA and Khan, R and Irfan, M and Shamail, F and Zia, F and Asif, MG}, title = {Impact of Histological Type and Grade on the Diagnostic Accuracy of Intraoperative Frozen Section for Detecting Breast Cancer Metastasis to Axillary Sentinel Lymph Nodes.}, journal = {Cureus}, volume = {13}, number = {7}, pages = {e16146}, pmid = {34354885}, issn = {2168-8184}, abstract = {Introduction Intraoperative sentinel lymph node (SLN) evaluation is the standard of care in patients with clinically node-negative breast cancer. The most common histological subtype of breast carcinoma is invasive ductal carcinoma (IDC), followed by invasive lobular carcinoma (ILC). Alternatively, histological grades vary from grades G1 to G3. Therefore, in this study, we evaluated the diagnostic accuracy of frozen section (FS) for detecting breast cancer metastasis to SLNs with respect to histological subtypes and grades. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, from January 2013 till December 2020, over a duration of eight years. A total of 540 cases of primary breast cancer, undergoing upfront breast surgery were included in the study. Intraoperatively, SLNs were identified and sent for FS. After FS reporting, the remaining tissue was submitted for final (paraffin) section examination after formalin fixation, and results of FS and final (paraffin) sections were compared. Results The mean age of the patients included in the study was 52.05±12.42 years, and the median number of SLNs was three (ranging from one to 14). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of intraoperative FS were 88.2%, 100%, 100%, 92.5%, and 95.2%, respectively. The sensitivity of FS for IDC was 88.3%, whereas it was 85.7% for ILC. Alternatively, the sensitivity of FS for grade G1, G2, and G3 tumors was 78.3%, 91.5%, and 90.2%, respectively. The false-negative rate for grade G1 tumors was 21.7%, which was higher than G2 and G3 tumors (8.5% and 9.8%, respectively). Similarly, the false-negative rate for cases where the number of SLNs was more than three was only 5.4%, which was lower than cases with a single and two to three SLNs sent on FS (23.1 and 14.7%, respectively). Conclusion The sensitivity of intraoperative FS for detecting ILC metastasis to axillary SLNs was not substantially different from IDC; however, histological grade affects the sensitivity of FS diagnosis, with lower-grade tumors having low sensitivity. Moreover, increasing the number of SLNs sent intraoperatively on FS improves the sensitivity of FS for detecting breast cancer metastasis to axillary SLNs.}, } @article {pmid34352627, year = {2021}, author = {Shelly, S and Liraz Zaltsman, S and Ben-Gal, O and Dayan, A and Ganmore, I and Shemesh, C and Atrakchi, D and Garra, S and Ravid, O and Rand, D and Israelov, H and Alon, T and Lichtenstein, G and Sharabi, S and Last, D and Gosselet, F and Rosen, V and Burstein, G and Friedlander, A and Harel, R and Vogel, G and Schnaider Beeri, M and Mardor, Y and Lampl, Y and Fleminger, G and Cooper, I}, title = {Potential neurotoxicity of titanium implants: Prospective, in-vivo and in-vitro study.}, journal = {Biomaterials}, volume = {276}, number = {}, pages = {121039}, doi = {10.1016/j.biomaterials.2021.121039}, pmid = {34352627}, issn = {1878-5905}, mesh = {Animals ; Endothelial Cells ; Humans ; Male ; Mice ; *Nanoparticles ; Prospective Studies ; Prostheses and Implants/adverse effects ; Rats ; *Titanium/toxicity ; }, abstract = {Titanium dioxide (TiO2) is a frequently used biomaterial, particularly in orthopedic and dental implants, and it is considered an inert and benign compound. This has resulted in toxicological scrutiny for TiO2 in the past decade, with numerus studies showing potential pathologic downstream effects. Herein we describe case report of a 77-year-old male with subacute CNS dysfunction, secondary to breakdown of a titanium-based carotid stent and leading to blood levels 1000 times higher (3 ppm) than the reported normal. We prospectively collected tissues adjacent to orthopedic implants and found a positive correlation between titanium concentration and time of implant in the body (r = 0.67, p < 0.02). Rats bearing titanium implants or intravascularly treated with TiO2 nanoparticles (TiNP) exhibited memory impairments. A human blood-brain barrier (BBB) in-vitro model exposed to TiNP showed paracellular leakiness, which was corroborated in-vivo with the decrease of key BBB transcripts in isolated blood vessels from hippocampi harvested from TiNP-treated mice. Titanium particles rapidly internalized into brain-like endothelial cells via caveolae-mediated endocytosis and macropinocytosis and induced pro-inflammatory reaction with increased expression of pro-inflammatory genes and proteins. Immune reaction was mediated partially by IL-1R and IL-6. In summary, we show that high levels of titanium accumulate in humans adjacent to orthopedic implants, and our in-vivo and in-vitro studies suggest it may be neurotoxic.}, } @article {pmid34350113, year = {2021}, author = {Luz, FAC and Araújo, RA and Silva, MJB}, title = {Decreased Survival of Invasive Ductal Breast Cancer Patients With Two Macrometastatic Lymph Nodes Among Few Resected Ones: Should Current Sentinel-Lymph-Node Guidelines Be Revised?.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {669890}, pmid = {34350113}, issn = {2234-943X}, abstract = {PURPOSE: Sentinel-lymph-node (SLN) biopsy (SLB) is an efficient and safe axillary surgical approach with decreased morbidity than total axillary lymph node dissection (ALND) in initial patients (T1-T2). Current guidelines strongly suggest avoiding completion of ALND in patients with one or two positive SLNs that will be submitted to whole-breast radiation therapy, but must be done when three SLNs are affected.

METHODS: We performed a SEER-based study with breast invasive ductal carcinoma patients treated between 2010 and 2015. Optimal cutoffs of positive LNs predictive of survival were obtained with ROC curves and survival as a continuous variable. Bias was reduced through propensity score matching. Cox regression was employed to estimate prognosis. Nomograms were constructed to analyze the predictive value of clinicopathological factors for axillary burden.

RESULTS: Of 43,239 initial patients that had one to three analyzed LNs, only 425 had two positive LNs and matched analysis demonstrated no survival difference versus pN2 patients [HR: 0.960 (0.635-1.452), p = 0.846]. The positive-to-analyzed LN proportion demonstrated a strong prognostic factor for a low rate (1 positive to ≤1.5 analyzed) [HR = 1.567 (1.156-2.126), p = 0.004], and analysis derived from the results demonstrated that a "negative LN margin" improves survival. Nomograms shows that tumor size is the main factor of axillary burden.

CONCLUSION: Macrometastasis of two LNs is a poor prognostic factor, similar to pN2, in SLNB (-like) patients; more extensive studies including preconized therapies must be done in order to corroborate or refute the resistance of this prognostic difference in patients with two macrometastatic lymph nodes within few resected.}, } @article {pmid34349234, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Validity of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {948-958}, pmid = {34349234}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; 90IF0121/ACL/ACL HHS/United States ; 90IF0121/ACL/ACL HHS/United States ; }, mesh = {Catheters, Indwelling ; Humans ; Psychometrics ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: Descriptive Psychometrics Study OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).

SETTING: Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.

METHODS: Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".

RESULTS: Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.

CONCLUSIONS: The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.}, } @article {pmid34347221, year = {2021}, author = {Kedrzycki, MS and Leiloglou, M and Chalau, V and Chiarini, N and Thiruchelvam, PTR and Hadjiminas, DJ and Hogben, KR and Rashid, F and Ramakrishnan, R and Darzi, AW and Elson, DS and Leff, DR}, title = {The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery.}, journal = {Annals of surgical oncology}, volume = {28}, number = {10}, pages = {5617-5625}, pmid = {34347221}, issn = {1534-4681}, support = {208857/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_18050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; Female ; Humans ; *Indocyanine Green ; Margins of Excision ; Mastectomy, Segmental ; Prospective Studies ; }, abstract = {BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system.

METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts.

RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099).

DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.}, } @article {pmid34345005, year = {2021}, author = {Tractenberg, RE and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH and Groah, SL}, title = {Reliability of the Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB) who void or use indwelling catheters.}, journal = {Spinal cord}, volume = {59}, number = {9}, pages = {939-947}, pmid = {34345005}, issn = {1476-5624}, support = {90IF0121/ACL/ACL HHS/United States ; 385077//Craig H. Neilsen Foundation/ ; }, mesh = {Bayes Theorem ; Catheters, Indwelling ; Humans ; Reproducibility of Results ; *Spinal Cord Injuries/complications/diagnosis ; Surveys and Questionnaires ; United States ; *Urinary Bladder, Neurogenic/diagnosis/etiology ; }, abstract = {STUDY DESIGN: This is a descriptive psychometrics study.

OBJECTIVES: Neurogenic lower urinary tract dysfunction (NLUTD), also called Neurogenic Bladder (NB), is a common and disruptive condition in a variety of neurologic diagnoses. Our team developed patient-centered instruments, Urinary Symptom Questionnaires for people with neurogenic bladder (USQNB), specific to people with NLUTD who manage their bladders with intermittent catheterization (IC), indwelling catheters (IDC), or who void (V). This article reports evidence of reliability of the IDC and V instruments.

SETTING: Online surveys completed by individuals in the United States with NLUTD due to spinal cord injury (SCI), or multiple sclerosis (MS) who manage their bladder with IDC (SCI, n = 306), or by voiding (SCI, n = 103; MS, n = 383).

METHODS: Reliability estimates were based on endorsement of the items on the USQNB-IDC and USQNB-V. Reliability evidence was representativeness of these symptoms for a national sample (by determining if endorsement > 10%); internal consistency estimates (by Cronbach's alpha and item correlation coefficient, ICC); and interrelatedness of the items (by inferred Bayesian network, BN). We also tested whether a one-factor conceptualization of "urinary symptoms in NLUTD" was supportable for either instrument.

RESULTS: All items were endorsed by >20% of our samples. Urine quality symptoms tended to be the most commonly endorsed on both instruments. Cronbach's alpha and ICC estimates were high (>0.74), but not suggestive of redundancy. BNs showed interpretable associations among the items, and did not discover uninterpretable or unexpected associations. Neither instrument fit a one-factor model, as expected.

CONCLUSIONS: The USQNB-IDC and USQNB-V instruments show sufficient, multidimensional reliability for implementation and further study.}, } @article {pmid34340541, year = {2021}, author = {Pickford, AK and Michel-Todó, L and Dupuy, F and Mayor, A and Alonso, PL and Lavazec, C and Cortés, A}, title = {Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0163621}, pmid = {34340541}, issn = {2150-7511}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antigens, Protozoan/immunology ; *Gene Expression Profiling ; *Genetic Variation ; Host-Parasite Interactions/*genetics/immunology ; Humans ; Malaria, Falciparum/immunology/*parasitology ; Plasmodium falciparum/*genetics/immunology ; Protozoan Proteins/*genetics/immunology ; Transcriptome ; }, abstract = {Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families. Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs. In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression. Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites. Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature. Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state. Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages. IMPORTANCE The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites. However, how these genes are expressed under the natural conditions of the human circulation and how their expression is affected by passage through transmission stages are not well understood. Here, we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences with in vitro-cultured parasites. We also show that, during transmission stages, the previous expression patterns for many CVG families are lost, and new patterns are established.}, } @article {pmid34336518, year = {2021}, author = {McCray, E and Naron, R and White, S and Messersmith, S and Stewart, C}, title = {Metastatic Breast Cancer Masked as Constipation.}, journal = {Cureus}, volume = {13}, number = {6}, pages = {e16031}, pmid = {34336518}, issn = {2168-8184}, abstract = {Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic. A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer. Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.}, } @article {pmid34336079, year = {2021}, author = {Kapoor, MM and Moseley, TW}, title = {Fluid-filled breast: A unique clinical presentation of invasive micropapillary carcinoma.}, journal = {Radiology case reports}, volume = {16}, number = {9}, pages = {2731-2735}, pmid = {34336079}, issn = {1930-0433}, abstract = {Invasive micropapillary carcinoma is a rare variant of invasive ductal carcinoma of the breast. This variant has been described as clinically aggressive due to its high frequency of lymphovascular invasion, axillary nodal metastases, and a greater degree of loco-regional recurrence. Invasive micropapillary carcinoma can have a variety of imaging presentations, typically presenting as an irregular mass. This case report describes a unique presentation of invasive micropapillary carcinoma and illustrates the propensity of invasive micropapillary carcinoma to secrete fluid and have a lack of regional lymphadenopathy. The challenges of the accompanying diagnostic imaging-work up are discussed.}, } @article {pmid34331497, year = {2021}, author = {Chu, SY and Foong, JH and Lee, J and Ben-David, BM and Barlow, SM and Hsu, C}, title = {Oral diadochokinetic rates across languages: Multilingual speakers comparison.}, journal = {International journal of language & communication disorders}, volume = {56}, number = {5}, pages = {1026-1036}, doi = {10.1111/1460-6984.12653}, pmid = {34331497}, issn = {1460-6984}, mesh = {Aging ; Female ; Humans ; Language ; Male ; *Multilingualism ; Speech ; Speech Production Measurement ; }, abstract = {BACKGROUND: It is unclear whether oral diadochokinetic rate (oral-DDK) performance is affected by different languages within a multilingual country.

AIMS: This study investigated the effects of age, sex, and stimulus type (real word in L1, L2 vs. non-word) on oral-DDK rates among healthy Malaysian-Malay speakers in order to establish language- and age-sensitive norms. The second aim was to compared the nonword 'pataka' oral-DDK rates produced by Malaysian-Malay speakers on currently available normative data for Hebrew speakers and Malaysian-Mandarin speakers.

METHODS & PROCEDURES: Oral-DDK performance of 90 participants (aged 20-77 years) using nonword ('pataka'), Malay real word ('patahkan'), and English real word ('buttercake') was audio recorded. The number of syllables produced in 8 seconds was calculated. Mixed analysis of variance (ANOVA) was conducted to examine the effects of stimulus type (nonword, Malay, and English real word), sex (male, female), age (younger, 20-40 years; middle, 41-60 years; older, ≥61 years), and their interactions on the oral-DDK rate. Data obtained were also compared with the raw data of Malaysian-Mandarin and Hebrew speakers from the previous studies.

OUTCOMES & RESULTS: A normative oral-DDK rate has been established for healthy Malaysian-Malay speakers. The oral-DDK rate was significantly affected by stimuli (p < 0.001). Malay real word showed the slowest rate, whereas there was no significant difference between English real word and nonword. The oral-DDK rate for Malay speakers was significantly higher than Mandarin and Hebrew speakers across stimuli (all p < 0.01). Interestingly, oral-DDK rates were not affected by age group for Malay speakers.

Stimuli type and language affect the oral-DDK rate, indicating that speech-language therapists should consider using language-specific norms when assessing multilingual speakers.

WHAT THIS PAPER ADDS: What is already known on the subject Age, sex, and language are factors that need to be considered when developing oral-DDK normative protocol. It is unclear whether oral-DDK performance is affected by different languages within a multilingual country. What this paper adds to existing knowledge No ageing effect across real word versus nonword on oral-DDK performance was observed among Malaysian-Malay speakers, contrasting with current available literature that speech movements slow down as we age. Additionally, Malaysian-Malay speakers have faster oral-DDK rates than Malaysian-Mandarin and Hebrew speakers across all stimuli. What are the potential or actual clinical implications of this work? Establishing normative data of different languages will enable speech-language therapists to select the appropriate reference dataset based on the language mastery of these multilingual speakers.}, } @article {pmid34330920, year = {2021}, author = {Thomson-Luque, R and Votborg-Novél, L and Ndovie, W and Andrade, CM and Niangaly, M and Attipa, C and Lima, NF and Coulibaly, D and Doumtabe, D and Guindo, B and Tangara, B and Maiga, F and Kone, AK and Traore, K and Kayentao, K and Ongoiba, A and Doumbo, S and Thera, MA and Traoré, B and Seydel, K and Osório, NS and Portugal, S}, title = {Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4711}, pmid = {34330920}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI099628/AI/NIAID NIH HHS/United States ; }, mesh = {Blood Circulation Time ; Erythrocytes/parasitology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Bacterial ; Gene Ontology ; Genes, Bacterial/genetics ; Humans ; Malaria, Falciparum/*blood/parasitology/physiopathology ; Parasitemia/*blood/parasitology/physiopathology ; Plasmodium falciparum/*genetics/physiology ; }, abstract = {Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum's tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.}, } @article {pmid34326994, year = {2021}, author = {Sazawal, S and Ryckman, KK and Mittal, H and Khanam, R and Nisar, I and Jasper, E and Rahman, S and Mehmood, U and Das, S and Bedell, B and Chowdhury, NH and Barkat, A and Dutta, A and Deb, S and Ahmed, S and Khalid, F and Raqib, R and Ilyas, M and Nizar, A and Ali, SM and Manu, A and Yoshida, S and Baqui, AH and Jehan, F and Dhingra, U and Bahl, R}, title = {Using AMANHI-ACT cohorts for external validation of Iowa new-born metabolic profiles based models for postnatal gestational age estimation.}, journal = {Journal of global health}, volume = {11}, number = {}, pages = {04044}, pmid = {34326994}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Cohort Studies ; *Gestational Age ; Humans ; Infant, Newborn ; *Metabolome ; *Models, Biological ; Reproducibility of Results ; }, abstract = {BACKGROUND: Globally, 15 million infants are born preterm and another 23.2 million infants are born small for gestational age (SGA). Determining burden of preterm and SGA births, is essential for effective planning, modification of health policies and targeting interventions for reducing these outcomes for which accurate estimation of gestational age (GA) is crucial. Early pregnancy ultrasound measurements, last menstrual period and post-natal neonatal examinations have proven to be not feasible or inaccurate. Proposed algorithms for GA estimation in western populations, based on routine new-born screening, though promising, lack validation in developing country settings. We evaluated the hypothesis that models developed in USA, also predicted GA in cohorts of South Asia (575) and Sub-Saharan Africa (736) with same precision.

METHODS: Dried heel prick blood spots collected 24-72 hours after birth from 1311 new-borns, were analysed for standard metabolic screen. Regression algorithm based, GA estimates were computed from metabolic data and compared to first trimester ultrasound validated, GA estimates (gold standard).

RESULTS: Overall Algorithm (metabolites + birthweight) estimated GA to within an average deviation of 1.5 weeks. The estimated GA was within the gold standard estimate by 1 and 2 weeks for 70.5% and 90.1% new-borns respectively. Inclusion of birthweight in the metabolites model improved discriminatory ability of this method, and showed promise in identifying preterm births. Receiver operating characteristic (ROC) curve analysis estimated an area under curve of 0.86 (conservative bootstrap 95% confidence interval (CI) = 0.83 to 0.89); P < 0.001) and Youden Index of 0.58 (95% CI = 0.51 to 0.64) with a corresponding sensitivity of 80.7% and specificity of 77.6%.

CONCLUSION: Metabolic gestational age dating offers a novel means for accurate population-level gestational age estimates in LMIC settings and help preterm birth surveillance initiatives. Further research should focus on use of machine learning and newer analytic methods broader than conventional metabolic screen analytes, enabling incorporation of region-specific analytes and cord blood metabolic profiles models predicting gestational age accurately.}, } @article {pmid34323051, year = {2021}, author = {Deng, Y and Li, FL and Qin, HY and Zhou, YY and Zhou, QQ and Mei, J and Li, L and Liu, HH and Wang, YZ and Bu, H and Bao, J}, title = {[Application Test of the AI-Automatic Diagnostic System for Ki-67 in Breast Cancer].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {52}, number = {4}, pages = {693-697}, pmid = {34323051}, issn = {1672-173X}, mesh = {Artificial Intelligence ; *Breast Neoplasms/diagnosis ; Female ; Humans ; Ki-67 Antigen ; Microscopy ; Reproducibility of Results ; }, abstract = {OBJECTIVE: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results.

METHODS: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient (ICC) was used to evaluate the correlation.

RESULTS: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal.

CONCLUSION: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.}, } @article {pmid34321100, year = {2021}, author = {Meyer, D and Kames, J and Bar, H and Komar, AA and Alexaki, A and Ibla, J and Hunt, RC and Santana-Quintero, LV and Golikov, A and DiCuccio, M and Kimchi-Sarfaty, C}, title = {Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {122}, pmid = {34321100}, issn = {1756-994X}, support = {R01 HL151392/HL/NHLBI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Codon ; *Codon Usage ; Computational Biology/*methods ; *Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Kaplan-Meier Estimate ; Neoplasms/*diagnosis/*genetics/mortality ; Prognosis ; Transcriptome ; }, abstract = {BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.

METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.

RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.

CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.}, } @article {pmid34320711, year = {2021}, author = {Fan, T and Wang, CQ and Li, XT and Yang, H and Zhou, J and Song, YJ}, title = {MiR-22-3p Suppresses Cell Migration and Invasion by Targeting PLAGL2 in Breast Cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {31}, number = {8}, pages = {937-940}, doi = {10.29271/jcpsp.2021.08.937}, pmid = {34320711}, issn = {1681-7168}, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *MicroRNAs/genetics ; RNA-Binding Proteins/genetics ; Transcription Factors/genetics ; }, abstract = {OBJECTIVE: To investigate the expression of miR-22-3p in breast cancer and the mechanism of targeting PLAGL2 to inhibit the invasion and migration in human breast cancer.

STUDY DESIGN: An experimental study.

PLACE AND DURATION OF STUDY: Department of Oncology and Department of General Surgery, The People's Hospital of China Three Gorges University, China, from March 2019 to December 2020.

METHODOLOGY: The miR-22-3p expression level in 41 paired human primary breast invasive ductal carcinoma tissues and para-cancer tissues was obtained by real-time fluorescence quantitative reverse transcriptase PCR (qRT-PCR). The effect of miR-22-3p on the proliferation of breast cancer cells was detected by growth curve method. Online software TargetScan was used to predict the target genes of miR-22-3p. The prediction results were verified by luciferase reporter gene assay and qRT⁃PCR.

RESULTS: MiR-22-3p expression was significantly decreased in the breast cancer tissues than in para⁃carcinoma normal breast tissues (p<0.05). Over-expression of miR-22-3p can inhibit the proliferation of MCF-7 cells significantly. Pleomorphic adenoma gene-like protein 2(PLAGL2) is the predicted target gene of miR-22-3p. MiR-22-3p binds to its predicted target gene PLAGL2-3'UTR. The expression of miR-22-3p was negatively correlated with PLAGL2 in MCF-7 cells.

CONCLUSION: MiR-22-3p could suppress the proliferation of breast cancer by targeting PLAGL2. This suggests that miR-22-3p may be a strategy of choice for targeted therapy of breast cancer. Key Words: Breast cancer, MiR-22-3p, PLAGL2, Cell proliferation.}, } @article {pmid34319162, year = {2022}, author = {Chung, HL and Tso, HH and Middleton, LP and Sun, J and Leung, JWT}, title = {Axillary Nodal Metastases in Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma: Comparison of Node Detection and Morphology by Ultrasound.}, journal = {AJR. American journal of roentgenology}, volume = {218}, number = {1}, pages = {33-41}, doi = {10.2214/AJR.21.26135}, pmid = {34319162}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis/*diagnostic imaging ; Male ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; Young Adult ; }, abstract = {BACKGROUND. Invasive lobular carcinoma is more subtle on imaging compared with invasive ductal carcinoma; nodal metastases may also differ on imaging between these two. OBJECTIVE. The purpose of this study was to determine whether invasive lobular carcinoma and invasive ductal carcinoma differ in the detection rate by ultrasound (US) of metastatic axillary nodes and in the metastatic nodes' US characteristics. METHODS. This retrospective study included 695 women (median age, 53 years) who had breast cancer in a total of 723 breasts (76 lobular, 586 ductal, 61 mixed ductal and lobular histology) with biopsy-proven axillary nodal metastases and who underwent pretreatment US. A single breast radiologist reviewed US images in patients with suspicious nodes on US and classified number of nodes, size, and morphology. Morphologic assessment used a previously described classification according to the relationship between node cortex and hilum. Nodal findings were compared between lobular and ductal carcinoma. A second radiologist independently classified node morphology in 241 cancers to assess interreader agreement. RESULTS. A total of 99 metastatic axillary nodes (15 lobular, 66 ductal, 18 mixed histology) were not visualized on US and were diagnosed by surgical biopsy. The remaining 624 metastatic nodes (61 lobular, 520 ductal, 43 mixed ductal and lobular histology) were visualized on US and diagnosed by US-guided fine-needle aspiration. US detected the metastatic nodes in 80.3% for lobular carcinoma versus 88.7% for ductal carcinoma (p = .04). Among metastatic nodes detected by US, retrospective review identified three or more abnormal nodes in 50.8% of lobular carcinoma versus 69.2% of ductal carcinoma (p = .003); node size was 2.0 cm or smaller in 65.6% for lobular carcinoma versus 47.3% for ductal carcinoma (p = .03); morphology was type III or IV (diffuse cortical thickening without hilar mass effect) rather than type V or VI (marked cortical thickening with hilar mass effect) in 68.9% for lobular carcinoma versus 28.8% for ductal carcinoma (p < .001). Interreader agreement assessment for morphology exhibited a kappa coefficient of 0.63 (95% CI, 0.54-0.73). CONCLUSION. US detects a lower percentage of nodal metastases in lobular than in ductal carcinoma. Nodal metastases in lobular carcinoma more commonly show diffuse cortical thickening and with less hilar mass effect. CLINICAL IMPACT. A lower threshold may be warranted to recommend biopsy of suspicious axillary nodes detected on US in patients with lobular carcinoma.}, } @article {pmid34319011, year = {2021}, author = {Demir, S and Nawroth, PP and Herzig, S and Ekim Üstünel, B}, title = {Emerging Targets in Type 2 Diabetes and Diabetic Complications.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {18}, pages = {e2100275}, pmid = {34319011}, issn = {2198-3844}, support = {EK 108/1-1//German Research Foundation (DFG)/ ; 1118//DFG - Collaborative Research Center/ ; }, mesh = {Diabetes Complications/*drug therapy/*physiopathology ; Diabetes Mellitus, Type 2/*drug therapy/*physiopathology ; Humans ; Hypoglycemic Agents/*therapeutic use ; }, abstract = {Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.}, } @article {pmid34318951, year = {2021}, author = {Lopez Salazar, V and Karikari, RA and Li, L and El-Merahbi, R and Troullinaki, M and Wu, M and Wiedemann, T and Walth, A and Gil Lozano, M and Rohm, M and Herzig, S and Georgiadi, A}, title = {WITHDRAWN: Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35 Suppl 1}, number = {}, pages = {}, doi = {10.1096/fasebj.2021.35.S1.00447}, pmid = {34318951}, issn = {1530-6860}, support = {2017/18//DAAD Forschungsstipendien - Promotionen in Deutschland/ ; }, abstract = {Withdrawal: Valeria Lopez Salazar, Rhoda Anane Karikari, Lun Li, Rabih El-Merahbi, Maria Troullinaki, Moya Wu, Tobias Wiedemann, Alina Walth, Manuel Gil Lozano, Maria Rohm, Stephan Herzig, Anastasia Georgiadi. Adipocyte Deletion of ADAM17 Leads to Insulin Resistance in Association with Age and HFD in Mice (2021). The FASEB Journal. 35:s1. doi: 10.1096/fasebj.2021.35.S1.00447. The above abstract, published online on May 14, 2021 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, FASEB, and Wiley Periodicals Inc. The withdrawal is due to a request made by the authors prior to publication. The Publisher apologizes that this abstract was published in error.}, } @article {pmid34316107, year = {2021}, author = {Ramani, SK and Rastogi, A and Nair, N and Shet, TM and Thakur, MH}, title = {Hyperechoic Lesions on Breast Ultrasound: All Things Bright and Beautiful?.}, journal = {The Indian journal of radiology & imaging}, volume = {31}, number = {1}, pages = {18-23}, pmid = {34316107}, issn = {0971-3026}, abstract = {Ultrasound (US) lexicon of the Breast Imaging Reporting and Data System (BI-RADS) defines an echogenic breast mass as a lesion that is hyperechoic in comparison with subcutaneous adipose tissue. However, at sonography, only 0.6 to 5.6% of breast masses are echogenic and the majority of these lesions are benign. approximately, 0.5% of malignant breast lesions appear hyperechoic. The various benign pathologic entities that appear echogenic on US are lipoma, hematoma, seroma, fat necrosis, abscess, pseudoangiomatous stromal hyperplasia, galactocele, etc. The malignant diagnoses that may present as hyperechoic lesions on breast US are invasive ductal carcinoma, invasive lobular carcinoma, metastasis, lymphoma, and angiosarcoma. Echogenic breast masses need to be correlated with mammographic findings and clinical history. Lesions with worrisome features such as a spiculated margin, interval enlargement, interval vascularity, or association with suspicious microcalcifications on mammography require biopsy. In this article, we would like to present a pictorial review of patients who presented to our department with echogenic breast masses and were subsequently found to have various malignant as well as benign etiologies on histopathology.}, } @article {pmid34315379, year = {2021}, author = {Rafiq, MT and Hamid, MSA and Hafiz, E and Chaudhary, FA and Khan, MI}, title = {Feasibility and Acceptability of Instructions of Daily Care in Overweight and Obese Knee Osteoarthritis Participants.}, journal = {Current rheumatology reviews}, volume = {17}, number = {4}, pages = {421-427}, doi = {10.2174/1573397117666210727095552}, pmid = {34315379}, issn = {1875-6360}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Feasibility Studies ; Humans ; *Obesity/complications ; *Osteoarthritis, Knee/drug therapy/therapy ; *Overweight/complications ; Pain ; *Self Care/methods ; Treatment Outcome ; }, abstract = {INTRODUCTION: Knee Osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of the study was to assess the feasibility and acceptability of Instructions of Daily Care (IDC) on pain, mobility, and Body Mass Index (BMI) among knee OA participants who are overweight or obese.

MATERIALS AND METHODS: The study was an open-label randomized controlled trial of six weeks. Forty overweight and obese participants with knee OA were randomly divided into two groups by a computer-generated number. The participants in the Instruction Group (IG) were provided with leaflets explaining IDC for the duration of six weeks. Both groups were instructed to take low doses of the non-steroid anti-inflammatory drug (NSAIDs) on alternate days. The outcome measures were pain, mobility and BMI. The feasibility and acceptability of knee pain and mobility were assessed using a questionnaire designed by experts in rehabilitation.

RESULTS: Participants in the IG reported more statistically significant pain relief as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index score (p=0.001) and improvement in mobility (p=0.000) assessed by the Timed Up and Go test score after six weeks compared to the Control Group (CG). Both groups did not demonstrate any significant change in BMI (p-value > 0.05). The results of descriptive statistics showed a significantly higher satisfaction score for participants who received a combination of IDC and NSAIDs, indicating an acceptable intervention.

CONCLUSION: The IDC is effective and acceptable in terms of improving pain and mobility and should be recommended as the usual care of treatment.}, } @article {pmid34314763, year = {2021}, author = {Offermann, A and Joerg, V and Hupe, MC and Becker, F and Müller, M and Brägelmann, J and Kirfel, J and Merseburger, AS and Sailer, V and Tharun, L and Perner, S}, title = {CDK19 as a diagnostic marker for high-grade prostatic intraepithelial neoplasia.}, journal = {Human pathology}, volume = {117}, number = {}, pages = {60-67}, doi = {10.1016/j.humpath.2021.07.006}, pmid = {34314763}, issn = {1532-8392}, mesh = {Aged ; Biomarkers, Tumor/*metabolism ; Cyclin-Dependent Kinases/analysis/*biosynthesis ; Humans ; Male ; Middle Aged ; Prostatic Intraepithelial Neoplasia/*diagnosis/pathology ; Prostatic Neoplasms/*diagnosis/pathology ; }, abstract = {High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.}, } @article {pmid34313861, year = {2022}, author = {Andrén, P and Jakubovski, E and Murphy, TL and Woitecki, K and Tarnok, Z and Zimmerman-Brenner, S and van de Griendt, J and Debes, NM and Viefhaus, P and Robinson, S and Roessner, V and Ganos, C and Szejko, N and Müller-Vahl, KR and Cath, D and Hartmann, A and Verdellen, C}, title = {European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part II: psychological interventions.}, journal = {European child & adolescent psychiatry}, volume = {31}, number = {3}, pages = {403-423}, pmid = {34313861}, issn = {1435-165X}, mesh = {Behavior Therapy ; Humans ; Psychosocial Intervention ; *Tic Disorders ; *Tics/therapy ; *Tourette Syndrome/psychology/therapy ; }, abstract = {Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011-2019 and a manual search for the years 2019-2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.}, } @article {pmid34307863, year = {2021}, author = {Wang, D and Zhang, J and Jin, J and Liu, D and Mao, X}, title = {Rapid global path planning algorithm for unmanned surface vehicles in large-scale and multi-island marine environments.}, journal = {PeerJ. Computer science}, volume = {7}, number = {}, pages = {e612}, pmid = {34307863}, issn = {2376-5992}, abstract = {A global path planning algorithm for unmanned surface vehicles (USVs) with short time requirements in large-scale and complex multi-island marine environments is proposed. The fast marching method-based path planning for USVs is performed on grid maps, resulting in a decrease in computer efficiency for larger maps. This can be mitigated by improving the algorithm process. In the proposed algorithm, path planning is performed twice in maps with different spatial resolution (SR) grids. The first path planning is performed in a low SR grid map to determine effective regions, and the second is executed in a high SR grid map to rapidly acquire the final high precision global path. In each path planning process, a modified inshore-distance-constraint fast marching square (IDC-FM[2]) method is applied. Based on this method, the path portions around an obstacle can be constrained within a region determined by two inshore-distance parameters. The path planning results show that the proposed algorithm can generate smooth and safe global paths wherein the portions that bypass obstacles can be flexibly modified. Compared with the path planning based on the IDC-FM[2] method applied to a single grid map, this algorithm can significantly improve the calculation efficiency while maintaining the precision of the planned path.}, } @article {pmid34297787, year = {2021}, author = {Ahmed, F and Adnan, M and Malik, A and Tariq, S and Kamal, F and Ijaz, B}, title = {Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0255243}, pmid = {34297787}, issn = {1932-6203}, mesh = {Adult ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Pakistan ; Smad2 Protein/genetics/metabolism ; Smad4 Protein/genetics/metabolism ; Transforming Growth Factor beta/genetics/*metabolism ; }, abstract = {Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient's data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to this in silico analysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of the TGF-β1 signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients' biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulate SMAD4 and SMAD2 expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.}, } @article {pmid34297443, year = {2021}, author = {Ikeda, J and Ohe, C and Ohsugi, H and Matsuda, T and Tsuta, K and Kinoshita, H}, title = {Association of intraductal carcinoma of the prostate detected by initial histological specimen and neuroendocrine prostate cancer: A report of three cases.}, journal = {Pathology international}, volume = {71}, number = {9}, pages = {621-626}, doi = {10.1111/pin.13137}, pmid = {34297443}, issn = {1440-1827}, mesh = {Adenocarcinoma/*diagnosis/pathology ; Aged ; Androgen Antagonists/therapeutic use ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Carcinoma, Neuroendocrine/*diagnosis/pathology ; Humans ; Male ; Prostate/pathology ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/*diagnosis/pathology ; }, abstract = {We present three cases of neuroendocrine prostate cancer (NEPC) and histologically investigate the association of intraductal carcinoma of the prostate (IDC-P) and NEPC. Case 1 was a 76-year-old man who had NEPC identified by repeated biopsy specimens when his prostate-specific antigen (PSA) level became elevated 8 years after the initiation of androgen deprivation therapy (ADT). Case 2 was a 70-year-old man who had NEPC detected when multiple bone metastases were found 3 years after the initiation of ADT. Case 3 was a 70-year-old man who was diagnosed with NEPC based on histological examination of transurethral resected specimens. The histological findings in these three cases showed mixed neuroendocrine carcinoma-acinar adenocarcinoma with various proportions of both components. In all three cases, the neuroendocrine carcinoma components were positive for synaptophysin and chromogranin A, whereas the adenocarcinoma components were positive for PSA and NKX3.1. When we retrospectively reviewed the initial hematoxylin and eosin-stained slides, IDC-P was detected in all three cases. Furthermore, we collected nine additional cases of NEPC and found that all six cases with initial biopsy specimens available had an IDC-P component. Detecting IDC-P on initial histological specimens of the prostate may predict transformation to NEPC.}, } @article {pmid34295827, year = {2021}, author = {Yan, Z and Qu, J and Li, Z and Yi, J and Su, Y and Lin, Q and Yu, G and Lin, Z and Yin, W and Lu, F and Liu, J}, title = {NEK7 Promotes Pancreatic Cancer Progression And Its Expression Is Correlated With Poor Prognosis.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {705797}, pmid = {34295827}, issn = {2234-943X}, abstract = {The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.}, } @article {pmid34295085, year = {2021}, author = {Keelara, AG and Satish, C and Rudresh, HK and Harish, K and Kapali, AS}, title = {Rotter's Lymph Nodes-Do We Really Need to Remove During Axillary Clearance?.}, journal = {Indian journal of surgical oncology}, volume = {12}, number = {2}, pages = {397-400}, pmid = {34295085}, issn = {0975-7651}, abstract = {Surgical management of node positive breast cancer requires axillary dissection. Interpectoral nodes (IPNs) or Rotter's nodes removal is controversial as there is hardly any tissue in this region. IPNs involvement is rarely seen among breast cancer patients. Developing an effective protocol for surgical management of axilla is necessary for uniformity, to reduce the risk of regional recurrence and to avoid the morbidity of interpectoral lymphatic tissue clearance. This study aimed to evaluate the detection of lymph nodes in Rotter's region and positive metastasis rate of IPNs in patients with node positive breast cancer for analyzing the prognostic and therapeutic value of IPN excision during axillary clearance. Fifty-six patients undergoing axillary clearance, aged ≥ 18 years, were studied. Patients with recurrence or those who underwent neoadjuvant chemotherapy were excluded. Baseline investigations were done pre-operatively along with core needle biopsy, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 status. Association between IPN status, age, and clinicopathological parameters were assessed by Kruskal Wallis and Chi-square test using R v 3.6.0. P value of ≤ 0.05 was considered statistically significant. Majority of patients had upper outer quadrant tumor location (22/56), and the most common histopathological type was invasive ductal carcinoma (46/56). IPNs were identified in 35.71% (20/56) of 56 patients, with metastasis prevalence of 27.27% (9/33 node positive patients). Patients having IPN metastasis had larger tumor size, later TNM classification, lower ER/PR, and higher Ki-67 positivity. Dissection of IPNs can be practiced routinely during axillary clearance and should be subjected to histopathological examination separately.}, } @article {pmid34293926, year = {2021}, author = {Chen, X and Li, X and Wang, J and Zhao, L and Peng, X and Zhang, C and Liu, K and Huang, G and Lai, Y}, title = {Breast invasive ductal carcinoma diagnosis with a three-miRNA panel in serum.}, journal = {Biomarkers in medicine}, volume = {15}, number = {12}, pages = {951-963}, doi = {10.2217/bmm-2020-0785}, pmid = {34293926}, issn = {1752-0371}, mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/blood/diagnosis/*genetics ; Carcinoma, Ductal, Breast/blood/diagnosis/*genetics ; Cohort Studies ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; }, abstract = {Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC = 0.880, sensitivity = 86.25%, specificity = 81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.}, } @article {pmid34293708, year = {2021}, author = {Okcu, O and Öztürk, Ç and Şen, B and Arpa, M and Bedir, R}, title = {Tumor Budding is a reliable predictor for death and metastasis in invasive ductal breast cancer and correlates with other prognostic clinicopathological parameters.}, journal = {Annals of diagnostic pathology}, volume = {54}, number = {}, pages = {151792}, doi = {10.1016/j.anndiagpath.2021.151792}, pmid = {34293708}, issn = {1532-8198}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/diagnosis/*pathology ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND AND OBJECTIVE: Breast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches. Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.

MATERIALS AND METHODS: 311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.

RESULTS: We determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.

CONCLUSION: Tumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.}, } @article {pmid34290853, year = {2021}, author = {Elgazar, A and Awad, AK and Mnadal, D and Elbadawy, MA and Elseidy, SA}, title = {Synchronous breast invasive ductal carcinoma and clear cell renal carcinoma: case report and a review of literature.}, journal = {Journal of surgical case reports}, volume = {2021}, number = {7}, pages = {rjab317}, pmid = {34290853}, issn = {2042-8812}, abstract = {Multiple primary tumors' incidence is rare, yet more rare is the incidence of multiple primary malignant tumors. Co-occurring tumors can be divided into synchronous and non-synchronous. Synchronous tumors are those tumors that present within a period not >6 months from each other. To define synchronous malignant tumors: metastasis should not be present, both tumors have to show criteria of malignancy, and they should differ pathologically from each other. Breast cancer is the most common tumor to be associated with other primaries especially; colorectal cancer, endometrial and ovarian cancer, yet the occurrence of invasive ductal carcinoma with clear cell renal cancer is uncommon. In our case, we present a 59-year-old female with invasive ductal carcinoma and clear cell renal carcinoma.}, } @article {pmid34288516, year = {2021}, author = {Muley, C and Bartelt, A}, title = {Fuse your mitochondria, lose appetite: an anorexic, anti-obesity sphingolipid.}, journal = {EMBO molecular medicine}, volume = {13}, number = {8}, pages = {e14618}, pmid = {34288516}, issn = {1757-4684}, mesh = {*Appetite ; Ceramides ; Humans ; Mitochondria ; Obesity ; *Sphingolipids ; }, abstract = {Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side chain length determines lipotoxicity of ceramides, as those composed of C16:0 or C18:0 side chains are toxic whereas those with C24:0 or C24:1 are not (Meikle and Summers 2017). Counteracting the deleterious effects of high-fat diets (HFDs) rich in saturated fat either by inhibiting synthesis or by promoting degradation of ceramides mitigates insulin resistance and ectopic lipid accumulation (Meikle and Summers 2017). However, drugs that safely and selectively target ceramide metabolism have failed to translate into metabolic benefit in human trials so far.}, } @article {pmid34287742, year = {2021}, author = {Horiguchi, J and Nakashoji, A and Kawahara, N and Matsui, A and Kinoshita, T}, title = {Chemotherapy resumption in breast cancer patient after COVID-19.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {170}, pmid = {34287742}, issn = {2198-7793}, abstract = {BACKGROUND: While many studies have verified the effect of recent anti-cancer treatment in patients with COVID-19, there are no data on the optimal time for cancer treatment resumption, as well as the safety of chemotherapy in COVID-19 patients. As many cancer patients are recovering from COVID-19, there is an urgent need for reliable clinical information. Herein, we report a case of invasive ductal carcinoma in which we were able to successfully resume chemotherapy after infection with SAR-CoV-2.

CASE PRESENTATION: The patient was a 38-year-old non-smoking Japanese woman with no significant medical history. She had fever on days 5 and 6 of her second course of adjuvant FEC therapy, and on day 7, she tested positive for SARS-CoV-2 by RT-PCR. She was hospitalized for 11 days. We resumed the therapy on day 25 after discharge, as she had no remaining clinical symptoms. The patient completed four courses of the initial chemotherapy without any major adverse events nor the recurrence of COVID-19, and subsequently completed four courses of docetaxel as her second regimen therapy.

CONCLUSIONS: Evaluating the risk for each patient is essential when resuming anti-cancer therapy in cancer patient's post-COVID-19.}, } @article {pmid34279157, year = {2021}, author = {Ren, X and Ju, Y and Wang, C and Wei, R and Sun, H and Zhang, Q}, title = {MARCKS on Tumor-Associated Macrophages is Correlated with Immune Infiltrates and Poor Prognosis in Hepatocellular Carcinoma.}, journal = {Cancer investigation}, volume = {39}, number = {9}, pages = {756-768}, doi = {10.1080/07357907.2021.1950757}, pmid = {34279157}, issn = {1532-4192}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Carcinoma, Hepatocellular/*genetics/metabolism/pathology ; Cell Line, Tumor ; Exosomes/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/*genetics/metabolism/pathology ; MicroRNAs/genetics ; Myristoylated Alanine-Rich C Kinase Substrate/*genetics/metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; THP-1 Cells ; Tumor-Associated Macrophages/*metabolism ; }, abstract = {BACKGROUND: Hepatocellular carcinoma is the fourth most common cause of cancer-related death. However, the cross-talk between tumor immune microenvironment and hepatocellular carcinoma (HCC) remains unclear.

MATERIAL AND METHODS: We analyzed the expression of miR-143-3p in exosomes from different HCC cell lines. Differentially expressed genes (DEGs) in Tumor-associated macrophages (TAMs) co-cultured with HCC cell lines were overlapped with miR-143-3p target genes. We used the Oncomine, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) databases to assess Myristoylated alanine-rich C-kinase substrate (MARCKS) expression in various types of cancers. The relationship between patient clinicopathological characteristics and MARCKS expression level was identified using the Kaplan-Meier plotter database. Last, we analyzed how MARCKS expression correlated with immune infiltration makers using the TCGA database, Tumor IMmune Estimation Resource (TIMER), and Gene Expression Profiling Interactive Analysis (GEPIA).

RESULTS: Exosomal miR-143-3p was elevated after IL-6 treatment in the HCC cell line. MARCKS, a target gene of miR-143-3p, was up-regulated in Tumor-associated macrophages co-cultured with high-metastatic-potential HCC cell line. MARCKS expression was identified as significantly correlated with outcome in multiple types of cancer, especially in HCC. High MARCKS expression level was associated with poorer overall survival (OS), Progress-free survival (PFS), and also with patient gender, race, hepatitis virus background, stage, grade, AJCC_T, and vascular invasion. MARCKS was positively associated with levels of T follicular helper cells (TFH) (R = .48, p < .001), T helper type 2 (Th2) cells (R = .47, p < .001), macrophages (R = .41, p ≤ .001), T helper cells (R = .40, p < .001), T helper type 1 (Th1) cells (R = .38, p < .001), T cells (R = .34, p < .001), NK CD56bright cells (R = .34, p < .001) and immature DC (iDC) (R = .33, p < .001), and negatively associated with levels of T helper 17 (Th17) cells. Also, MARCKS may influence the M2 polarization and immune escape.

CONCLUSION: The present study suggests that MARCKS on TAMs is associated with poor prognosis and immune cell infiltration in HCC.}, } @article {pmid34278746, year = {2021}, author = {Qi, H and Schmöhl, F and Li, X and Qian, X and Tabler, CT and Bennewitz, K and Sticht, C and Morgenstern, J and Fleming, T and Volk, N and Hausser, I and Heidenreich, E and Hell, R and Nawroth, PP and Kroll, J}, title = {Reduced Acrolein Detoxification in akr1a1a Zebrafish Mutants Causes Impaired Insulin Receptor Signaling and Microvascular Alterations.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {18}, pages = {e2101281}, pmid = {34278746}, issn = {2198-3844}, support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; IRTG1874/2 DIAMICOM//Deutsche Forschungsgemeinschaft/ ; CSC 201806230275//China Scholarship Council/ ; 81800390//National Natural Science Foundation of China/ ; }, mesh = {Acrolein/*metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Disease Models, Animal ; Glucose/*metabolism ; Homeostasis ; Larva/metabolism ; Liver/*metabolism ; Metabolomics/methods ; Receptor, Insulin/*metabolism ; Signal Transduction ; Transcriptome ; Zebrafish/metabolism ; }, abstract = {Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a[-/-] zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a[-/-] larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a[-/-] larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a[-/-] mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.}, } @article {pmid34277087, year = {2021}, author = {Haque, W and Verma, V and Adeberg, S and Rustomily, R and Lo, S and Butler, EB and Teh, BS}, title = {Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {26}, number = {3}, pages = {341-351}, pmid = {34277087}, issn = {1507-1367}, abstract = {BACKGROUND: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.

MATERIALS AND METHODS: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.

RESULTS: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT.

CONCLUSIONS: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.}, } @article {pmid34276997, year = {2021}, author = {Gortman, A and Aherne, NJ and Westhuyzen, J and Amalaseelan, JV and Dwyer, PM and Hoffmann, M and Last, AT and Shakespeare, TP}, title = {Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up.}, journal = {Molecular and clinical oncology}, volume = {15}, number = {3}, pages = {178}, pmid = {34276997}, issn = {2049-9469}, abstract = {Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.}, } @article {pmid34272624, year = {2021}, author = {Considine, B and Adeniran, A and Hurwitz, ME}, title = {Current Understanding and Management of Intraductal Carcinoma of the Prostate.}, journal = {Current oncology reports}, volume = {23}, number = {9}, pages = {110}, pmid = {34272624}, issn = {1534-6269}, mesh = {Carcinoma, Ductal/*genetics/pathology/therapy ; DNA Mismatch Repair/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; *Microsatellite Instability ; *Mutation ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/pathology/therapy ; Signal Transduction/genetics ; }, abstract = {PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.

RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.}, } @article {pmid34269730, year = {2021}, author = {Scolozzi, V and Giancipoli, RG and Macciomei, MC and Vigna, L and Leccisotti, L}, title = {Cavernous Hemangioma: A Potential Pitfall at Delayed 18F-FDG PET/CT Scan.}, journal = {Clinical nuclear medicine}, volume = {46}, number = {12}, pages = {e584-e586}, doi = {10.1097/RLU.0000000000003808}, pmid = {34269730}, issn = {1536-0229}, mesh = {Aged ; Female ; *Fluorodeoxyglucose F18 ; *Hemangioma, Cavernous ; Humans ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; }, abstract = {We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.}, } @article {pmid34263155, year = {2021}, author = {Coşkun Bilge, A and Aydın, H and Bostancı, IE and Tanişman, Ö and Saygılı Öz, D}, title = {Comparison of the Magnetic Resonance Imaging Findings of Paget's Disease of the Breast and Malignant Tumor Invasion of the Nipple-Areola Complex.}, journal = {European journal of breast health}, volume = {17}, number = {3}, pages = {265-273}, pmid = {34263155}, issn = {2587-0831}, abstract = {OBJECTIVE: We aimed to investigate the distinction between Paget's disease of the breast (PDB) and malignant tumor invasion of nipple-areolar complex (MTION) with Magnetic resonance imaging (MRI) findings without the need for skin punch biopsy.

MATERIALS AND METHODS: MRI findings of 16 patients with pathologically proven PDB and 11 patients with pathologically proven MTION were reviewed retrospectively. MRI images were assessed for nipple morphological changes; areolar-periareolar skin changes; thickness, classification, and kinetic characteristics of the nipple-areolar complex (NAC) enhancement; morphological pattern, size, and pathological diagnosis of concomitant malignant lesions; kinetic characteristics of the concomitant malignant lesions enhancement; continuity of enhancement between the nipple and closest concomitant malignant lesion; similarity of enhancement kinetics of the NAC and concomitant malignant lesions; and nipple-to-malignant lesion distance in both patient groups.

RESULTS: Areolar-periareolar skin thickening was statistically different between the patient groups. Enhancement kinetic pattern was classified as persistent in four patients with MTION and plateau in seven patients with PDB. Moreover, NAC enhancement kinetic characteristics were statistically different between the groups. Invasive ductal carcinoma was detected in three patients with PDB and five patients with MTION. A statistically significant difference in malignant lesion pathological types was detected between the patient groups.

CONCLUSION: The significant MRI findings in patients with MTION diagnosed as invasive ductal carcinoma were areolar-periareolar skin thickening and asymmetric NAC enhancement with persistent kinetics pattern. In patients diagnosed with ductal carcinoma in situ, a plateau pattern of asymmetric NAC enhancement without any areolar-periareolar skin changes on MRI may indicate PDB.}, } @article {pmid34259124, year = {2021}, author = {Lifshin, U and Mikulincer, M}, title = {Further evidence for motivated helplessness in the context of the COVID-19 outbreak: the case of Argentina before and during the pandemic.}, journal = {The Journal of social psychology}, volume = {161}, number = {4}, pages = {452-465}, doi = {10.1080/00224545.2021.1918618}, pmid = {34259124}, issn = {1940-1183}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Anxiety/*psychology ; Argentina ; COVID-19/*psychology ; Fear/*psychology ; Female ; Humans ; Male ; Middle Aged ; *Motivation ; Pandemics ; SARS-CoV-2 ; Young Adult ; }, abstract = {According to the motivated helplessness hypothesis, a sense of helplessness in coping with threats in a specific domain can serve an anxiety-buffering function. The purpose of this study was to test this hypothesis in the context of the coronavirus (COVID-19) pandemic in Argentina, using data collected before and during the pandemic. Findings supported the motivated helplessness hypothesis: Whereas feelings of helplessness to avoid being infected with COVID-19 were positively related to fear of being infected with COVID-19 and state anxiety before the pandemic, these feelings were negatively related to fear of being infected (and not directly related to state anxiety) during the pandemic. These findings demonstrate the specificity of the motivated helplessness effect and further establish this effect in the context of the COVID-19 pandemic.}, } @article {pmid34258723, year = {2021}, author = {Naffouje, SA and Sabesan, A and Hoover, SJ and Lee, MC and Laronga, C}, title = {Surgical Management of the Axilla of HER2+ Breast Cancer in the Z1071 Era: A Propensity-Score-Matched Analysis of the NCDB.}, journal = {Annals of surgical oncology}, volume = {28}, number = {13}, pages = {8777-8788}, pmid = {34258723}, issn = {1534-4681}, mesh = {Axilla ; *Breast Neoplasms/surgery ; Female ; Humans ; Lymph Node Excision ; Neoadjuvant Therapy ; Propensity Score ; Sentinel Lymph Node Biopsy ; }, abstract = {INTRODUCTION: We aim to analyze survival outcomes for sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in human epidermal growth factor receptor (HER2)+ infiltrative ductal carcinoma (IDC) that demonstrate complete clinical response (cCR) to neoadjuvant systemic therapy (NAST) after initial presentation with clinical N1 (cN1) disease.

METHODS: NCDB 2004-2017 was utilized for the analysis. Female patients with unilateral HER2+ IDC, stage cT1-T4 cN1, who demonstrated cCR to NAST with reported definitive axillary surgical management were included. Patients were propensity score matched, and overall survival (OS) was compared. Cox regression analysis was used to identify survival predictors.

RESULTS: 6453 patients were selected, of whom 2461 (38.1%) had SLNB and 3992 (69.1%) had ALND as definitive axillary surgical management. The trend of SLNB utilization increased from 20% in 2012 to 50% in 2017. A total of 2454 patients were matched from each group with adequate adjustment for all variables. There was no difference in OS between SLNB versus ALND (84.03 ± 0.36 versus 84.62 ± 0.42 months; p = 0.522). Cox regression identified age, cT stage, primary tumor response to NAST, ypN+, and endocrine therapy as significant OS predictors. In subgroup analysis of patients with ypN+ who had SLNB as a definitive procedure, primary tumor response to NAST and continuation of adjuvant chemotherapy were associated with improved OS.

CONCLUSION: In cN1 HER2+ IDC patients who demonstrate cCR to NAST, SLNB is a reasonable definitive procedure for axillary management with comparable OS outcomes to ALND. However, higher-level data are required to determine the appropriate management in the case of ypN+.}, } @article {pmid34257000, year = {2022}, author = {Cernusco, NLV and Bianco, PD and Romano, M and Muraglia, A and Rossi, G and Giri, MG and Guariglia, S and Lombardi, D and Pellini, F and Cavedon, C and Pollini, GP and Mazzarotto, R}, title = {Long-Term Outcomes Using Electron IOERT APBI for Early Stage Breast Cancer: The Verona University Hospital Experience.}, journal = {Clinical breast cancer}, volume = {22}, number = {2}, pages = {e167-e172}, doi = {10.1016/j.clbc.2021.05.015}, pmid = {34257000}, issn = {1938-0666}, mesh = {Adult ; Breast Neoplasms/pathology/surgery/*therapy ; Electrons/*therapeutic use ; Female ; Humans ; Italy ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Staging ; Radiotherapy Dosage ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {METHODS AND MATERIALS: From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status.

RESULTS: With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively.

CONCLUSION: Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.}, } @article {pmid34253952, year = {2022}, author = {Shoshani, A and Yaari, S}, title = {Parental Flow and Positive Emotions: Optimal Experiences in Parent-Child Interactions and Parents' Well-Being.}, journal = {Journal of happiness studies}, volume = {23}, number = {2}, pages = {789-811}, pmid = {34253952}, issn = {1389-4978}, abstract = {Flow is a mental state of thorough absorption and concentration in an activity, in which intrinsic motivation and enjoyment are maximized, and the individual achieves optimal performance. This study investigated how daily flow experiences during parents' interactions with their children contribute to parental well-being. The Day Reconstruction Method was completed by 832 employed Israeli parents of children aged 2 to 12, who reconstructed their experiences on three different working days over three weeks, and rated their levels of flow, as well as positive and negative affect for each experience. Participants also completed measures of subjective well-being and parental satisfaction and efficacy. The results indicated that parents' flow experiences during interactions with their children were positively related to parents' positive affect, self-efficacy and satisfaction, and greater subjective well-being. The findings underscore the importance for parental well-being of daily optimal experiences with their children.}, } @article {pmid34251074, year = {2021}, author = {Dabiri, C and Hotton, J and Wehbe, K and Gornes, H and Garbar, C and Guillemin, F and Ceccato, V}, title = {Assessment of the Grisotti oncoplastic procedure for the management of central breast tumors.}, journal = {The breast journal}, volume = {27}, number = {7}, pages = {595-602}, doi = {10.1111/tbj.14256}, pmid = {34251074}, issn = {1524-4741}, mesh = {Aged ; *Breast Neoplasms/surgery ; Female ; Humans ; *Mammaplasty/adverse effects ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Nipples/surgery ; Retrospective Studies ; }, abstract = {INTRODUCTION: The Grisotti technique consists to excise central breast tumor with nipple areolar and mobilize a dermo-glandular flap which is de-epithelized in order to reshape the breast and recreate an areola. The objective was to assess oncological results, postoperative side-effects, and patient and surgeon satisfaction rates resulting from this technique.

MATERIALS AND METHODS: From September 2016 to December 2019, 38 patients have been treated with a central breast tumor using the Grisotti technique.

RESULTS: The mean age was 61.6 ± 11. The median body mass index was 27 kg/m² [20-42]. Thirty one patients benefited from a sentinel lymph node dissection. Preoperative histology found a majority of invasive ductal carcinomas (IDC) (71%). There were no intraoperative complications, and the average operating time was 90 min [60-200]. Postoperative histology found IDC associated with ductal carcinoma in situ in 28 patients. The surgical margins were invaded in two patients (reoperated by mastectomy after adjuvant treatment) and invasion of a margin of less than 1 mm in another six patients (supplemented by re-excision). The main postoperative complications were an abscess of the operating site and a partial necrosis of the neo-areola. The appearance of the breasts after radiotherapy gives a high satisfaction rate, both for patients and for surgeons.

CONCLUSION: The Grisotti technique is an easily reproducible procedure without major complications. It makes it possible to perform a carcinological satisfactory central lumpectomy, correction of the central glandular defect, and reconstruction of a new areola.}, } @article {pmid34249415, year = {2021}, author = {Lin, Q and Chen, X and Meng, F and Ogawa, K and Li, M and Song, R and Zhang, S and Zhang, Z and Kong, X and Xu, Q and He, F and Liu, D and Bai, X and Sun, B and Hung, MC and Liu, L and Wands, JR and Dong, X}, title = {Multi-organ metastasis as destination for breast cancer cells guided by biomechanical architecture.}, journal = {American journal of cancer research}, volume = {11}, number = {6}, pages = {2537-2567}, pmid = {34249415}, issn = {2156-6976}, abstract = {A majority of breast cancer patients die of widespread aggressive multidrug-resistant tumors. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase and oncofetal antigen involved in embryogenesis. To illustrate if ASPH could be targeted for metastatic breast cancer, embedded and on-top three-dimensional (3-D) cultures, 3-D invasion, mammosphere formation, immunofluorescence, immunohistochemistry, Western blot, co-IP and microarray were conducted. In vitro metastasis was developed to imitate how cancer cells invade basement membrane at the primary site, transendothelially migrate, consequently colonize and outgrow at distant sites. Orthotopic and experimental pulmonary metastatic (tail vein injection) murine models were established using stable breast cancer cell lines. Cox proportional hazards regression models and Kaplan-Meier plots were applied to assess clinical outcome of breast cancer patients. In adult non-cancerous breast tissue, ASPH is undetectable. Pathologically, ASPH expression re-emerged at ductal carcinoma in situ (DCIS), and enhanced with disease progression, from early-stage invasive ductal carcinoma (IDC) to late-stage carcinoma. ASPH at moderate to high levels contribute to aggressive molecular subtypes, early relapse or more frequent progression and metastases, whereas substantially shortened overall survival and disease-free survival of breast cancer patients. Through direct physical interactions with A disintegrin and metalloproteinase domain-containing protein (ADAM)-12/ADAM-15, ASPH could activate SRC cascade, thus upregulating downstream components attributed to multifaceted metastasis. ASPH-SRC axis initiated pro-invasive invadopodium formation causing breakdown/disorganization of extracellular matrix (ECM), simultaneously potentiated epithelial-mesenchymal transition (EMT), induced cancer stem cell markers (CD44 and EpCAM), enhanced mammosphere formation and intensified 3-dimentional invasion. Oncogenic SRC upregulated matrix metallopeptidases (MMPs) were assembled by invadopodia, acting as executive effectors for multi-step metastasis. ASPH-SRC signal guided multi-organ metastases (to lungs, liver, bone, spleen, lymph nodes, mesentery or colon) in immunocompromised mice. Malignant phenotypes induced by ASPH-SRC axis were reversed by the third-generation small molecule inhibitor (SMI) specifically against β-hydroxylase activity of ASPH in pre-clinical models of metastatic breast cancer. Collectively, ASPH could activate ADAMs-SRC-MMPs cascades to promote breast cancer tumor progression and metastasis. ASPH could direct invadopodium construction as a biomechanical sensor and pro-metastatic outlet. ASPH-mediated cancer progression could be specifically/efficiently subverted by SMIs of β-hydroxylase activity. Therefore, ASPH emerges as a therapeutic target for breast cancer.}, } @article {pmid34248562, year = {2021}, author = {Sato, F and Shimomura, A and Nakayama, K and Kawamura, Y and Hashimoto, K and Ishibashi, Y and Shimizu, C and Kitagawa, D}, title = {Breast Cancer Treatment in a Patient with Decubitus Ulcer Infection Secondary to Spina Bifida: Surgical Resection versus Neoadjuvant Chemotherapy.}, journal = {Case reports in oncology}, volume = {14}, number = {2}, pages = {944-949}, pmid = {34248562}, issn = {1662-6575}, abstract = {Spina bifida (SB) is a congenital neural tube defect that often presents with neurological disability and decubitus ulcers. A 66-year-old woman with SB presented to our hospital with decubitus ulcers and was treated by a plastic surgeon. She was referred to our department because of a mass measuring 5 × 4 cm in the superolateral quadrant of the right breast. The size of the right axillary lymph node (LN) was 2 × 1 cm. A core-needle biopsy revealed an invasive ductal carcinoma. Total mastectomy and axillary LN dissection were planned. However, 2 days prior to surgery, the size of the mass and the LN rapidly increased to 7 × 4 cm and 3 × 2 cm, respectively. Furthermore, the enlarged LN was close to the thoracodorsal artery. Since complete resection was difficult, neoadjuvant chemotherapy was also administered. On day 11 of neoadjuvant chemotherapy, the patient was febrile and developed a decubitus ulcer infection at the buttock. The neutrophil count was within normal limits; thus, she was not diagnosed with febrile neutropenia. Follow-up computed tomography revealed a shrinking of the mass to 5 × 4 cm after the first cycle of neoadjuvant chemotherapy. After 17 days of antibiotic therapy and drainage, total mastectomy and axillary LN dissection were performed. Due to the risk of recurrence of infection, adjuvant chemotherapy was discontinued and hormone therapy was initiated. In conclusion, indications for chemotherapy should be carefully evaluated in SB patients with lower limb paralysis and decubitus ulcers.}, } @article {pmid34248081, year = {2021}, author = {Hirabayashi, M and Ozawa, M and Kako, S and Ashihara, N and Kuraishi, Y and Kanai, K and Watanabe, T and Notake, T and Nobuoka, M and Iwaya, M and Umemura, T}, title = {[Pancreatic adenocarcinoma:a case containing a cyst enclosing a dilated tubular gland duct].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {118}, number = {7}, pages = {679-685}, doi = {10.11405/nisshoshi.118.679}, pmid = {34248081}, issn = {0446-6586}, mesh = {*Adenocarcinoma/diagnostic imaging/surgery ; Aged ; *Breast Neoplasms ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/surgery ; *Cysts ; Female ; Humans ; Mastectomy ; Pancreatectomy ; Pancreatic Ducts ; *Pancreatic Neoplasms/diagnostic imaging/surgery ; }, abstract = {This case report describes a 73-year-old woman with pancreatic adenocarcinoma who had undergone a colectomy for colorectal cancer in 1995 and a right mastectomy and axillary dissection for breast cancer in 2013. In January 2019, a tumor, approximately 20mm in diameter, was detected in the pancreatic body. It contained a cyst noted to have delayed perfusion towards the center on abdominal computed tomography. On T1-weighted magnetic resonance imaging (MRI), almost the entire tumor exhibited low intensity. On T2-weighted MRI, however, the tumor center displayed high intensity, the tumor wall displayed low intensity, and the outermost layer displayed high intensity. On endoscopic ultrasound, the tumor center displayed low echo density, the tumor wall had a slightly elevated echo density, and the outermost layer had a low echo density. A distal pancreatectomy was performed for a suspected metastatic pancreatic cancer, pancreatic neuroendocrine neoplasm, or invasive ductal carcinoma without tubular adenocarcinoma. Histopathological examination revealed that the tumor cells had formed atypical tubular gland ducts with a fibrous stroma in the background. The lesion differed from the histopathological findings of her previous colorectal and breast cancers, and it was ultimately diagnosed as a pancreatic ductal adenocarcinoma. The lumen of the cyst was covered with tumor cells identical to those of the atypical tubular gland ducts in the tumor parenchyma, suggesting that the cyst was a dilated tubular gland duct.}, } @article {pmid34246859, year = {2021}, author = {Maida, A and Zota, A and Vegiopoulos, A and Appak-Baskoy, S and Augustin, HG and Heikenwalder, M and Herzig, S and Rose, AJ}, title = {Corrigendum to "Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance" [The Journal of Nutritional Biochemistry 57 (2018) 189-196].}, journal = {The Journal of nutritional biochemistry}, volume = {97}, number = {}, pages = {108807}, doi = {10.1016/j.jnutbio.2021.108807}, pmid = {34246859}, issn = {1873-4847}, } @article {pmid34245220, year = {2022}, author = {Bodner, E and Bergman, YS and Ben-David, B and Palgi, Y}, title = {Vaccination anxiety when vaccinations are available: The role of existential concerns.}, journal = {Stress and health : journal of the International Society for the Investigation of Stress}, volume = {38}, number = {1}, pages = {111-118}, pmid = {34245220}, issn = {1532-2998}, mesh = {Anxiety ; *COVID-19 ; *COVID-19 Vaccines ; Communicable Disease Control ; Humans ; SARS-CoV-2 ; Vaccination ; }, abstract = {This study examined how existential fears are related to COVID-19 vaccination anxiety and followed the Terror Management Theory (TMT) by examining the contribution of two existential concerns, subjective nearness-to-death (SNtD) and death anxiety, to COVID-19 vaccination anxiety during the first month of COVID-19 vaccinations. Data were collected during January 2021, when Israel was in lockdown, from a convenience sample of 381 Jewish Israelis (M = 55.39, SD = 17.17). Participants completed questionnaires examining demographics, SNtD, death anxiety and COVID-19 vaccination anxiety. A hierarchical regression analysis examined the connections between these variables and COVID-19 vaccination anxiety while controlling for demographics and for receiving COVID-19 vaccinations. In line with the hypotheses, SNtD and death anxiety were each positively associated with COVID-19 vaccination anxiety, and death anxiety levels moderated the positive connection between SNtD and COVID-19 vaccination anxiety, as this association was not significant for individuals with low death anxiety. The findings of this study provide preliminary evidence concerning the role of death anxiety in moderating the effect that SNtD has on COVID-19 vaccination anxiety. These findings are in line with the TMT and justify further investigation and may be utilized in future research in order to address COVID-19 vaccination anxiety more effectively.}, } @article {pmid34243714, year = {2021}, author = {Chiong, F and Wasef, MS and Liew, KC and Cowan, R and Tsai, D and Lee, YP and Croft, L and Harris, O and Gwini, SM and Athan, E}, title = {The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {671}, pmid = {34243714}, issn = {1471-2334}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/mortality/surgery ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Pseudomonas Infections/*drug therapy/mortality/surgery ; *Pseudomonas aeruginosa ; *Referral and Consultation ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB.

METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality.

RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups.

CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.}, } @article {pmid34243615, year = {2021}, author = {Samanta, A and Sarkar, A}, title = {Altered expression of ERK, Cytochrome-c, and HSP70 triggers apoptosis in Quinacrine-exposed human invasive ductal carcinoma cells.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {139}, number = {}, pages = {111707}, doi = {10.1016/j.biopha.2021.111707}, pmid = {34243615}, issn = {1950-6007}, mesh = {Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/metabolism ; Carcinoma, Ductal/*drug therapy/*metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Cytochromes c/*metabolism ; Female ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; MAP Kinase Signaling System/*drug effects ; MCF-7 Cells ; Neoplasm Recurrence, Local/drug therapy/metabolism ; Quinacrine/*pharmacology ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; }, abstract = {Invasive ductal carcinoma (IDC) is the most recurrent cancer, accounting for 80% of all breast cancers worldwide. Originating from the milk duct, it eventually invades the fibrous tissue of the breast outside the duct, proliferation takes 1-2 months for each division. Quinacrine (QC), an FDA-approved small molecule, has been shown to have anti-cancer activity in numerous cancerous cell lines through diverse pathways; ultimately leading to cell death. Here, we have investigated the mode of action of QC in MCF7 cells. This study demonstrated the modulation of cellular cytoskeleton, such as the formation of distinct filopodial and lamellipodial structures and spikes, through the regulation of small-GTPases. We also observed that QC induces a signaling cascade by inducing apoptotic cell death by increasing ROS generation and altering HSP70 expression; which presumably involves ERK regulation. Our findings show that QC could be an attractive chemotherapeutic agent having a "shotgun" nature with potential of inducing different signaling pathways leading to apoptotic cell death. This opens new avenues for research on developing QC as an effective therapeutic agent for the treatment of invasive ductal carcinomas.}, } @article {pmid34242220, year = {2021}, author = {Xu, Z and Kurek, A and Cannon, SB and Beavis, WD}, title = {Predictions from algorithmic modeling result in better decisions than from data modeling for soybean iron deficiency chlorosis.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0240948}, pmid = {34242220}, issn = {1932-6203}, mesh = {*Algorithms ; Bayes Theorem ; Cluster Analysis ; *Iron Deficiencies ; Logistic Models ; Machine Learning ; *Models, Statistical ; Soybeans/*metabolism ; }, abstract = {In soybean variety development and genetic improvement projects, iron deficiency chlorosis (IDC) is visually assessed as an ordinal response variable. Linear Mixed Models for Genomic Prediction (GP) have been developed, compared, and used to select continuous plant traits such as yield, height, and maturity, but can be inappropriate for ordinal traits. Generalized Linear Mixed Models have been developed for GP of ordinal response variables. However, neither approach addresses the most important questions for cultivar development and genetic improvement: How frequently are the 'wrong' genotypes retained, and how often are the 'correct' genotypes discarded? The research objective reported herein was to compare outcomes from four data modeling and six algorithmic modeling GP methods applied to IDC using decision metrics appropriate for variety development and genetic improvement projects. Appropriate metrics for decision making consist of specificity, sensitivity, precision, decision accuracy, and area under the receiver operating characteristic curve. Data modeling methods for GP included ridge regression, logistic regression, penalized logistic regression, and Bayesian generalized linear regression. Algorithmic modeling methods include Random Forest, Gradient Boosting Machine, Support Vector Machine, K-Nearest Neighbors, Naïve Bayes, and Artificial Neural Network. We found that a Support Vector Machine model provided the most specific decisions of correctly discarding IDC susceptible genotypes, while a Random Forest model resulted in the best decisions of retaining IDC tolerant genotypes, as well as the best outcomes when considering all decision metrics. Overall, the predictions from algorithmic modeling result in better decisions than from data modeling methods applied to soybean IDC.}, } @article {pmid34238275, year = {2021}, author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K}, title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {790}, pmid = {34238275}, issn = {1471-2407}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; }, abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.

METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.

RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.

CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.}, } @article {pmid34237252, year = {2021}, author = {Loft, A and Alfaro, AJ and Schmidt, SF and Pedersen, FB and Terkelsen, MK and Puglia, M and Chow, KK and Feuchtinger, A and Troullinaki, M and Maida, A and Wolff, G and Sakurai, M and Berutti, R and Ekim Üstünel, B and Nawroth, P and Ravnskjaer, K and Diaz, MB and Blagoev, B and Herzig, S}, title = {Liver-fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication.}, journal = {Cell metabolism}, volume = {33}, number = {8}, pages = {1685-1700.e9}, doi = {10.1016/j.cmet.2021.06.005}, pmid = {34237252}, issn = {1932-7420}, mesh = {Communication ; *Gene Regulatory Networks ; Hepatocytes/metabolism ; Humans ; Liver/metabolism ; Liver Cirrhosis/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; }, abstract = {Liver fibrosis is a strong predictor of long-term mortality in individuals with metabolic-associated fatty liver disease; yet, the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely understood. Using cell-type-resolved genomics, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the transcription factor Elf-3 (ELF3) and zinc finger protein GLIS2 (GLIS2). Indeed, ELF3- and GLIS2-controlled fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell gene programs. Thus, interconnected transcription factor networks not only promoted hepatocyte dysfunction but also directed the intra-hepatic crosstalk necessary for NASH and fibrosis progression, implying that molecular "hub-centered" targeting strategies are superior to existing mono-target approaches as currently used in NASH therapy.}, } @article {pmid34230895, year = {2021}, author = {Muthumani, K and Xu, Z and Jeong, M and Maslow, JN and Kalyanaraman, VS and Srinivasan, A}, title = {Preexisting vs. de novo antibodies against SARS-CoV-2 in individuals without or with virus infection: impact on antibody therapy, vaccine research and serological testing.}, journal = {Translational medicine communications}, volume = {6}, number = {1}, pages = {13}, pmid = {34230895}, issn = {2396-832X}, abstract = {The causative agent of the ongoing pandemic in the world is SARS-CoV-2. The research on SARS-CoV-2 has progressed with lightning speed on various fronts, including clinical research and treatment, virology, epidemiology, drug development, and vaccine research. Recent studies reported that sera from healthy individuals, who were confirmed negative for SARS-CoV-2 by RT-PCR method, tested positive for antibodies against spike and nucleocapsid proteins of SARS-CoV-2. Further, such antibodies also exhibited neutralizing activity against the virus. These observations have prompted us to prepare a commentary on this topic. While the preexisting antibodies are likely to protect against SARS-CoV-2 infection, they may also complicate serological testing results. Another unknown is the influence of preexisting antibodies on immune responses in individuals receiving vaccines against SARS-CoV-2. The commentary identifies the potential limitations with the serological tests based on spike and nucleocapsid proteins as these tests may overestimate the seroprevalence due to cross-reactive antibodies. The inclusion of tests specific to SARS-CoV-2 (such as RBD of spike protein) could overcome these limitations.}, } @article {pmid34229990, year = {2021}, author = {Zeigerer, A}, title = {NAFLD - A rising metabolic disease.}, journal = {Molecular metabolism}, volume = {50}, number = {}, pages = {101274}, doi = {10.1016/j.molmet.2021.101274}, pmid = {34229990}, issn = {2212-8778}, mesh = {Animals ; Disease Models, Animal ; Humans ; Liver/*pathology ; Metabolic Diseases/drug therapy/*metabolism/pathology ; Non-alcoholic Fatty Liver Disease/drug therapy/*metabolism/pathology ; }, } @article {pmid34229213, year = {2021}, author = {Fosko, NK and Davis, CH and Koshenkov, VP and Kowzun, MJ}, title = {Simultaneous primary invasive breast carcinoma and ipsilateral cutaneous melanoma of the back: Surgical approach and considerations, a case report.}, journal = {International journal of surgery case reports}, volume = {84}, number = {}, pages = {106155}, pmid = {34229213}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: A patient presented with ipsilateral, synchronous primary malignancies of left upper back melanoma and left breast invasive ductal carcinoma. This complex presentation was managed with a multidisciplinary approach.

CASE PRESENTATION: A 61-year-old female presented with multiple cutaneous lesions, revealed to be several foci of melanoma in situ as well as a T4b melanoma of the left upper back. On staging work up, a left breast malignancy was incidentally discovered. Genetic testing did not delineate a relevant mutation to explain the synchronous malignancies. Multidisciplinary surgical planning entailed consideration of the lymphatic drainage patterns of the lesions, with both the upper back melanoma and breast carcinoma expected to drain to the left axilla. Ultimately, simultaneous resections of both malignancies were performed as well as concomitant left sentinel lymph node biopsies utilizing dual tracer technique.

CLINICAL DISCUSSION: Currently, cases of synchronous primary cutaneous melanoma and independent, ipsilateral primary breast carcinoma have not been examined, and thus surgical considerations for axillary staging in this circumstance have not been discussed. The existing literature instead explores the incidence and operative challenges of one malignancy following the other after an interval of time.

CONCLUSION: This case highlights the utility of a multidisciplinary team for complex oncologic presentations and discusses a creative surgical approach to address two simultaneous primary malignancies involving the left breast and ipsilateral skin of the back. This case emphasizes an exceedingly rare presentation and serves as an important example to educate medical professionals on the innovative and team-based approach to treatment.}, } @article {pmid34225099, year = {2021}, author = {Pariyar, M and Johns, A and Thorne, RF and Scott, RJ and Avery-Kiejda, KA}, title = {Copy number variation in triple negative breast cancer samples associated with lymph node metastasis.}, journal = {Neoplasia (New York, N.Y.)}, volume = {23}, number = {8}, pages = {743-753}, pmid = {34225099}, issn = {1476-5586}, mesh = {*Biomarkers, Tumor ; Chromosome Mapping ; Computational Biology/methods ; *DNA Copy Number Variations ; DNA Methylation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Ontology ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Molecular Sequence Annotation ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*etiology/mortality/*pathology ; }, abstract = {Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients. CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDCs), 12 lymph node metastases (LNmets), and 7 normal adjacent tissues (NATs); as well as in an independent cohort containing 70 TNBC IDCs and the same 7 NATs. CNV-associated genes were analyzed using GO-enrichment and Pathway analysis. The prognostic role for genes showing CNV-based changes in messenger RNA expression was determined using the Kaplan-Meier plotter database. For the IDCs, there were a number of variations that were common in both the study and independent cohorts in the amplified regions of 1q, 8q, 19 (p and q), 2p, 5p and the deleted regions in 8p followed by 5q, and 19p. The most frequently amplified regions in the LNmets of the study cohort were 4q28.3, 2p, 3q24, 1q21.2, 10p, 12p11.1, 8q, 20p11.22-20p11.21, 21q22.13, 6p22.1 and the most frequently deleted regions were in 1p36.23, 4q21.1 and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with LNmets. The LNmet-associated genes were highly enriched for "regulation of complement activation," "regulation of protein activation cascade," "regulation of humoral immune response," "oxytocin signalling pathway," and "TRAIL binding" pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse-free survival. This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.}, } @article {pmid34224950, year = {2021}, author = {Jones, BM and Green, S}, title = {Modern radiation techniques in early stage breast cancer for the breast radiologist.}, journal = {Clinical imaging}, volume = {80}, number = {}, pages = {19-25}, doi = {10.1016/j.clinimag.2021.06.035}, pmid = {34224950}, issn = {1873-4499}, mesh = {*Breast Neoplasms/diagnostic imaging/radiotherapy/surgery ; *COVID-19 ; Female ; Humans ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; Radiologists ; SARS-CoV-2 ; }, abstract = {Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are contemporary alternatives to conventional and standard hypofractionated whole breast irradiation (WBI), which shorten treatment from 3 to 6 weeks to 1-2 weeks for select patients. PBI and accelerated PBI (APBI) can be delivered with external beam radiation (3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT)), intraoperative radiation (IORT), or brachytherapy. These new radiation techniques offer the advantage of convenience and lower cost, which ultimately improves access to care. Globally, the COVID 19 pandemic has accelerated APBI/PBI and ultra-hypofractionated regimens into routine practice for carefully selected patients. Recent long-term data from randomized controlled trials (RCTs) have demonstrated these techniques are safe and effective in suitable patients demonstrating equivalent or improved local recurrence, acute/late toxicity, and cosmesis. PBI and APBI should be limited to low risk unifocal invasive ductal carcinoma and ductal carcinoma in situ with tumor size < 2 cm, clear margins (≥2 mm), ER+, and negative nodes. Based on the results from UK Fast-Forward and UK FAST ultra-hypofractionated breast radiation can be safely employed for early stage node negative patients, but is not yet considered an international standard of care. In this review, authors will appraise recent data for these shorter course radiation treatment regimens, as well as, considerations for breast radiologists including surveillance imaging and radiographic findings.}, } @article {pmid34223213, year = {2020}, author = {Carpinello, O and Aserlind, A and Chang, F and Sagoskin, A and Widra, E}, title = {Fertility preservation in an oncology patient who presented with positive human chorionic gonadotropin.}, journal = {F&S reports}, volume = {1}, number = {1}, pages = {51-53}, pmid = {34223213}, issn = {2666-3341}, abstract = {OBJECTIVE: To report the case of a woman who presented for fertility preservation before breast cancer treatment who was found to be pregnant with an undesired pregnancy.

DESIGN: Case report.

SETTING: Single infertility practice.

PATIENT: A 28-year-old woman with a new diagnosis of grade 3 invasive ductal carcinoma of the breast was planning to undergo oocyte cryopreservation and was found to be pregnant with an undesired pregnancy. She underwent a medical termination at a gestational age of 5 weeks 4 days. Neither the patient nor her oncology team wished to delay treatment more than was necessary. The physician and patient decided to initiate controlled ovarian hyperstimulation (COH) before her human chorionic gonadotropin (hCG) returned to normal.

INTERVENTIONS: COH in the setting of a positive quantitative hCG.

MAIN OUTCOME MEASURES: Number of metaphase II (MII) oocytes cryopreserved; doses of Gonal-F and Menopur; serum E2, follicle-stimulating hormone, luteinizing hormone, hCG levels.

RESULTS: COH began 7 days after passing the products of conception. Baseline labs demonstrated hCG at 222 mIU/mL, follicle-stimulating hormone at <0.10 mIU/mL, luteinizing hormone at <1.10 mIU/mL, and E2 at 147 pg/mL. She was started on an antagonist protocol with the use of 150 IU Gonal F and 75 IU Menopur. She was triggered on stimulation day 14 with 5,000 U hCG, and her peak E2 was 5,924 pg/mL. She ultimately had 18 oocytes retrieved, 12 of which were MII, one MI, and five germinal vesicle. All were vitrified.

CONCLUSIONS: COH can be achieved in the setting of low positive hCG levels with subsequent successful oocyte maturation. The threshold for hCG trigger to be ineffective in the setting of a positive hCG has yet to be determined.}, } @article {pmid34221657, year = {2021}, author = {Sprenger, J and Murray, C and Lad, J and Jones, B and Thomas, G and Nofech-Mozes, S and Khorasani, M and Vitkin, A}, title = {Toward a quantitative method for estimating tumour-stroma ratio in breast cancer using polarized light microscopy.}, journal = {Biomedical optics express}, volume = {12}, number = {6}, pages = {3241-3252}, pmid = {34221657}, issn = {2156-7085}, abstract = {The tumour-stroma ratio (TSR) has been explored as a useful source of prognostic information in various cancers, including colorectal, breast, and gastric. Despite research showing potential prognostic utility, its uptake into the clinic has been limited, in part due to challenges associated with subjectivity, reproducibility, and quantification. We have recently proposed a simple, robust, and quantifiable high-contrast method of imaging intra- and peri-tumoural stroma based on polarized light microscopy. Here we report on its use to quantify TSR in human breast cancer using unstained slides from 40 patient samples of invasive ductal carcinoma (IDC). Polarimetric results based on a stromal abundance metric correlated well with pathology designations, showing a statistically significant difference between high- and low-stroma samples as scored by two clinical pathologists. The described polarized light imaging methodology shows promise for use as a quantitative, automatic, and standardizable tool for quantifying TSR, potentially addressing some of the challenges associated with its current estimation.}, } @article {pmid34221278, year = {2021}, author = {Abedi, SM and Mardanshahi, A and Zeanali, R}, title = {Added diagnostic value of SPECT to evaluate bone metastases in breast cancer patients with normal whole body bone scan.}, journal = {Caspian journal of internal medicine}, volume = {12}, number = {3}, pages = {290-293}, pmid = {34221278}, issn = {2008-6164}, abstract = {BACKGROUND: In this research, we aimed to survey the added value of single photon emission computed tomography (SPECT) in comparison with planar whole body bone scan to visualize bone metastatic lesions in patients with breast cancer.

METHODS: A total of 80 patients with breast cancer (invasive ductal carcinoma) were examined with planar whole body bone scan and SPECT imaging using 99mTc-labelled methylene diphosphonate (99mTc-MDP). The patients with abnormal uptakes in SPECT imaging were also investigated with magnetic resonance imaging (MRI).

RESULTS: Among these 80 patients with normal whole body bone SPECT scan, 19 (23.25%) of them revealed abnormal 99mTc-MDP uptake in skeleton. Furthermore, these 19 patients were subjected to MRI and 3 (3.75%) of them were confirmed with metastatic bone lesion.

CONCLUSION: The obtained data suggest that SPECT possess the added diagnostic over planar whole body bone scan.}, } @article {pmid34219706, year = {2022}, author = {Avau, F and Chintinne, M and Baudry, S and Buxant, F}, title = {Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {5-13}, doi = {10.3233/BD-210001}, pmid = {34219706}, issn = {1558-1551}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary ; Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy ; Humans ; Male ; Mammography ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.}, } @article {pmid34207042, year = {2021}, author = {Timbres, J and Moss, C and Mera, A and Haire, A and Gillett, C and Van Hemelrijck, M and Sawyer, E}, title = {Survival Outcomes in Invasive Lobular Carcinoma Compared to Oestrogen Receptor-Positive Invasive Ductal Carcinoma.}, journal = {Cancers}, volume = {13}, number = {12}, pages = {}, pmid = {34207042}, issn = {2072-6694}, abstract = {Invasive lobular breast cancer (ILC) accounts for 10-15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan-Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2- ILC had worse survival compared to ER+HER2- IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2- IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population.}, } @article {pmid34205778, year = {2021}, author = {Gulde, S and Wiedemann, T and Schillmaier, M and Valença, I and Lupp, A and Steiger, K and Yen, HY and Bäuerle, S and Notni, J and Luque, R and Schmid, H and Schulz, S and Ankerst, DP and Schilling, F and Pellegata, NS}, title = {Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors.}, journal = {Cancers}, volume = {13}, number = {12}, pages = {}, pmid = {34205778}, issn = {2072-6694}, support = {391523415-SFB824//Deutsche Forschungsgemeinschaft/ ; 314061271-TRR 205//Deutsche Forschungsgemeinschaft/ ; 70112383//Deutsche Krebshilfe/ ; 2017.012.1//Wilhelm Sander-Stiftung/ ; }, abstract = {Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors' proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.}, } @article {pmid34204158, year = {2021}, author = {Itani, MM and Nassar, FJ and Tfayli, AH and Talhouk, RS and Chamandi, GK and Itani, ARS and Makoukji, J and Boustany, RN and Hou, L and Zgheib, NK and Nasr, RR}, title = {A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.}, journal = {International journal of molecular sciences}, volume = {22}, number = {11}, pages = {}, pmid = {34204158}, issn = {1422-0067}, support = {R. NASR Grant//Lebanese National Council for Scientific Research (CNRS-L)/ ; R NASR proposal//Medical Practice Plan, AUB/ ; R Nasr proposal//Northwestern University Kiphart award/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*diagnosis/genetics/pathology ; Circulating MicroRNA/*blood/*genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Statistics, Nonparametric ; Young Adult ; }, abstract = {Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.}, } @article {pmid34200336, year = {2021}, author = {Madhavan, BK and Han, Z and Singh, B and Bordt, N and Kaymak, S and Bandapalli, OR and Kihm, L and Shahzad, K and Isermann, B and Herzig, S and Nawroth, P and Kumar, V}, title = {Elevated Expression of the RAGE Variant-V in SCLC Mitigates the Effect of Chemotherapeutic Drugs.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34200336}, issn = {2072-6694}, support = {SFB 1118.//Deutsche Forschungsgemeinschaft/ ; GRK 1874-DIAMICOM//DIAMICOM/ ; }, abstract = {Small cell lung carcinoma (SCLC) is a highly aggressive malignancy with a very high mortality rate. A prominent part of this is because these carcinomas are refractory to chemotherapies, such as etoposide or cisplatin, making effective treatment almost impossible. Here, we report that elevated expression of the RAGE variant-V in SCLC promotes homology-directed DNA DSBs repair when challenged with anti-cancer drugs. This variant exclusively localizes to the nucleus, interacts with members of the double-strand break (DSB) repair machinery and thus promotes the recruitment of DSBs repair factors at the site of damage. Increased expression of this variant thus, promotes timely DNA repair. Congruently, the tumor cells expressing high levels of variant-V can tolerate chemotherapeutic drug treatment better than the RAGE depleted cells. Our findings reveal a yet undisclosed role of the RAGE variant-V in the homology-directed DNA repair. This variant thus can be a potential target to be considered for future therapeutic approaches in advanced SSLC.}, } @article {pmid34198195, year = {2021}, author = {Solomon, Z and Mikulincer, M and Ohry, A and Ginzburg, K}, title = {Prior trauma, PTSD long-term trajectories, and risk for PTSD during the COVID-19 pandemic: A 29-year longitudinal study.}, journal = {Journal of psychiatric research}, volume = {141}, number = {}, pages = {140-145}, pmid = {34198195}, issn = {1879-1379}, mesh = {*COVID-19 ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Pandemics ; *Prisoners of War ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology ; *Veterans ; }, abstract = {This study assessed the contributions of prior war captivity trauma, the appraisal of the current COVID-19 danger and its resemblance to the prior trauma, and long-term trajectories of posttraumatic stress disorder (PTSD) to risk for PTSD during the COVID-19 pandemic. Capitalizing on a 29-year longitudinal study with four previous assessments, two groups of Israeli veterans - ex-Prisoners-of-War (ex-POWs) of the 1973 Yom Kippur War and comparable combat veterans of the same war - were reassessed during the COVID-19 pandemic. Previous data were collected on their PTSD trajectory 18, 30, 35, and 42 years after the war and exposure to stressful life events after the war. Currently, we collected data on their PTSD during the COVID-19 pandemic and their appraisal of similarities of past trauma with the current pandemic. Previously traumatized ex-POWs were found to be more vulnerable and had significantly higher rates of PTSD and more intense PTSD during the current pandemic than comparable combat veterans. Moreover, veterans in both groups who perceived the current adversity (captivity, combat) as hindering their current coping were more likely to suffer from PTSD than veterans who perceived it as a facilitating or irrelevant experience. In addition, chronic and delayed trajectories of PTSD among ex-POWs increased the risk for PTSD during the pandemic, and lifetime PTSD mediated the effects of war captivity on PTSD during the current pandemic. These findings support the stress resolution perspective indicating that the response to previous trauma - PTSD and its trajectories - increased the risk of PTSD following subsequent exposure to stress.}, } @article {pmid34198053, year = {2021}, author = {Sela, Y and Bar-Or, RL and Kor, A and Lev-Ran, S}, title = {The Internet addiction test: Psychometric properties, socio-demographic risk factors and addictive co-morbidities in a large adult sample.}, journal = {Addictive behaviors}, volume = {122}, number = {}, pages = {107023}, doi = {10.1016/j.addbeh.2021.107023}, pmid = {34198053}, issn = {1873-6327}, mesh = {Adult ; *Behavior, Addictive/epidemiology ; Cross-Sectional Studies ; Humans ; Internet ; *Internet Addiction Disorder ; Prevalence ; Psychometrics ; Reproducibility of Results ; Risk Factors ; Surveys and Questionnaires ; }, abstract = {The Internet Addiction Test (IAT) (Young, 1998) is one of the most utilized diagnostic instruments to evaluate internet addiction. Despite the wide use of IAT in research and clinical settings, there is lack of an empirical validation of this scale among a largescale adult population. The present study aimed to: (1) investigate the psychometric properties of a Hebrew version of the IAT among large-scale Israeli adult sample. (2) Assess the socio-demographic characteristics of individuals who suffer from IA. (3) Assess the co-morbidity of IA in relation to substance and behavioral addictions. A cross sectional study was conducted, by constructing a representative sample (N = 4035) of the Jewish adult (18-70 y/o, M = 40.5, SD = 14.5) population in Israel. Participants responded an online survey, that measured IAT, socio-demographic characteristics, substance and behavioral addictions. Results showed that two-factor model (Emotional and Cognitive Preoccupation with the Internet and Loss of Control and Interference with Daily Life) has good psychometric properties and fits the data well. Young age, not being married (Risk Ratio [RR] = 1.98, 95% CI [1.51-2.63]), and having a low socio-economic status (RR = 1.41, 95% CI [1.05-1.90]) were found to be associated with IA. Drug (RR = 4.50, 95% CI [2.89-7.01]) and alcohol (RR = 3.54, 95% CI [1.50-5.42]) use disorders were associated with IA. High co-morbidity between behavioral addictions and IA was also found (RR = 15.24, 95% CI [11.17-20.78]). Overall, results show that the Hebrew version of the IAT is a valid and reliable instrument, and provide a comprehensive picture of IA prevalence and profile in adult Israeli sample.}, } @article {pmid34196595, year = {2023}, author = {Abdelsattar, JM and Afridi, FG and Dai, Z and Yousaf, N and Seldomridge, A and Battin, AO and Wen, S and Gray, D and Marsh, JW and Cowher, MS and Partin, JF and Hazard-Jenkins, H and Lupinacci, K}, title = {The Effect of Lumpectomy and Cavity Shave Margin Status on Recurrence and Survival in Breast-Conserving Surgery.}, journal = {The American surgeon}, volume = {89}, number = {3}, pages = {424-433}, doi = {10.1177/00031348211030464}, pmid = {34196595}, issn = {1555-9823}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery/pathology ; Mastectomy, Segmental/methods ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology ; Reoperation ; Mastectomy ; Retrospective Studies ; Margins of Excision ; *Carcinoma, Ductal, Breast/surgery/pathology ; }, abstract = {BACKGROUND/OBJECTIVE: Cavity shave margins (CSMs) decrease rate of positive margins and need for re-excision. Recurrence data following breast-conserving surgery (BCS) are not always available in large cancer registries. We sought to define our recurrence and survival data in BCS with routine excision of CSMs.

METHODS: A single institution, 10-year retrospective review of breast cancer patients who underwent BCS with routine CSMs was conducted. Cavity shave margin technique was standard. Cox proportional hazard analyses and the Kaplan-Meier method were used to estimate recurrence and survival.

RESULTS: Breast-conserving surgery with CSM was performed in 839 patients. Re-excision rate to achieve negative margins was 8.5%. Fifty-two patients (75%) underwent margin re-excision vs 18 patients (25%) underwent salvage mastectomy. Positive margin rate stratified by tumor histology was highest for invasive lobular carcinoma followed by mixed invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), followed by pure DCIS and lowest for IDC. Length of follow-up was (4.7 ± 2.6, years). Overall recurrence rate (locoregional and systemic) was 4.3%: highest in patients with negative lumpectomy margin but positive CSM (L-S+ = 15%) followed by positive lumpectomy and CSMs (L+S+ = 14%), followed by patients with positive lumpectomy margin but negative CSMs (L+S- = 13%) and lowest for negative lumpectomy and CSM (L-S- = 5%), (P = .0008). There was no difference in 5-year breast cancer-specific survival between the 4 subgroups: 96% for L-S-, 86.7% L-S+, 94.7% L+S+ and 90% L+S- (P = .094).

CONCLUSIONS: Recurrence following BCS with CSMs can be stratified based on both lumpectomy and cavity shave margin positivity. Routine excision of CSMs allows identification of these patient subsets.}, } @article {pmid34196203, year = {2021}, author = {Gity, M and Jafari, M and Olfatbakhsh, A and Rezaei Kalantari, K and Hashemi, E and Sari, F}, title = {Assessment of Ultrasound Features and BI-RADS Categories of Malignant Breast Masses in Women ≤40.}, journal = {Archives of Iranian medicine}, volume = {24}, number = {5}, pages = {383-389}, doi = {10.34172/aim.2021.55}, pmid = {34196203}, issn = {1735-3947}, mesh = {Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Retrospective Studies ; Ultrasonography ; *Ultrasonography, Mammary ; }, abstract = {BACKGROUND: To evaluate ultrasound (US) characteristics and BI-RADS (Breast imaging-reporting and data system) of malignant breast masses in women <40 years and to compare with older patients.

METHODS: In a retrospective, descriptive-analytical study, we assessed the US images and BI-RADS category of 78 malignant masses with a final pathology of invasive ductal carcinoma (IDC, NOS type).

RESULTS: Overall, the most frequent US descriptors of IDC were indistinct margin (45%), irregular shaped (63.5%), posterior shadowing (38.8%), heterogeneous internal echogenicity (56.3%) and non-parallel orientation (76.3%). In this study, most malignant masses of young patients were categorized as BI-RADS 4a while in the older patients (over 40), they were mostly BI-RADS 4b and 5 with P=0.03 and odds ratio (OR) of 2.57 (95% confidence interval (CI), 0.74-8.8). In addition, the mean dimension of the mass in young cases was greater (18.3 mm) compared with older patients (13.2 mm) with P value of 0.04 and OR of 3.8 (95% CI, 1.1-13.4).

CONCLUSION: Similar to previous studies, malignant masses were diagnosed in greater dimensions in younger cases which may be due to the delay in diagnosis, the rapid growth of the tumor and the absence of routine screening guidelines. Radiologists should be aware of the possibility of malignancy in palpable slightly suspicious masses (BI-RADS 4A) in young cases.}, } @article {pmid34196187, year = {2021}, author = {Tahmasebi, S and Almayali, AMJ and Arasteh, P and Akrami, M and Zangouri, V and Arasteh, P and Hosseini, SM and Salehi Nobandegani, A and Asgari, A and Sadeghi, E and Zahiri, L and Talei, A}, title = {Determinants of Prognosis in Triple-Negative Breast Cancer: Report from a Large Breast Cancer Registry.}, journal = {Archives of Iranian medicine}, volume = {24}, number = {4}, pages = {280-288}, doi = {10.34172/aim.2021.39}, pmid = {34196187}, issn = {1735-3947}, mesh = {Breast/pathology ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local/epidemiology/pathology ; Neoplasm Staging ; Prognosis ; Registries ; Retrospective Studies ; *Triple Negative Breast Neoplasms/epidemiology/pathology/surgery ; }, abstract = {BACKGROUND: The outcome of patients with triple-negative breast cancer (TNBC) is highly dependent on demographic factors and ethnicity. We aimed to evaluate the clinicopathological determinants of prognosis among women with TNBC using data from one of the largest breast cancer (BC) registries.

METHODS: A total of 6145 patients with BC from our referral center were evaluated from 1995 to 2018, among whom 523 had TNBC. The baseline, menstrual and reproductive, treatment and pathology related characteristics were evaluated.

RESULTS: Among TNBC patients, the rate of stage 3 and 4 BC (29.9% vs. 14.4% and 7.8% vs. 0% for stage 3 and 4, respectively; P<0.001), invasive ductal carcinoma (90.7% vs. 75.6%; P=0.004), nodal involvement (46.7% vs. 33.4%; P=0.026), mastectomy (57.3% vs. 37.8%; P=0.001) and axillary node dissection (76.7% vs. 59.8%; P=0.019) was significantly higher in the group that developed recurrence. Disease-free-survival was 80.6% (157.76 ± 9.48 months) and overall-survival was 90.1% (182.73 ± 3.28 months). For death, stage 3 BC (compared to stages 0 and 1 as base) showed a higher risk of earlier death (adjusted HR: 4.191, 95% CI=1.392-12.621; P=0.011). For recurrence, stage 3 BC (adjusted HR: 1.044, 95% CI=1.209-6.673; P=0.017) (compared to stages 0 and 1 as base) showed significantly higher risk for developing earlier recurrence. Moreover, those who had invasive ductal carcinoma (compared to other types of BCs) had a higher risk for developing earlier recurrence (adjusted HR: 3.307, 95% CI=1.191-0.724; P=0.012).

CONCLUSION: BC stage plays a significant role in both earlier recurrence and earlier mortality among patients with TNBC.}, } @article {pmid34194774, year = {2021}, author = {Uenaka, N and Yamamoto, S and Sato, S and Kudo, T and Adachi, S and Narui, K and Tanabe, M and Yamada, A and Ishikawa, T and Endo, I}, title = {Primary breast lymphoma initially diagnosed as invasive ductal carcinoma: A case report.}, journal = {Clinical case reports}, volume = {9}, number = {6}, pages = {e04189}, pmid = {34194774}, issn = {2050-0904}, abstract = {A malignant tumor in the breast may not be conclusive of breast cancer. It is important to keep the possibility of primary breast lymphoma in rare scenarios. For the diagnosis of primary breast lymphoma, immunohistochemical staining is necessary.}, } @article {pmid34194268, year = {2021}, author = {Almomen, A and Arafah, M and Alwhaibi, M and Alsaigh, N and Alshememry, A and Alsaleh, NB and Alrabeeah, D and Al Saleh, K and Alshamsan, A and Alkholief, M}, title = {Ceramide expression in relation to breast cancer molecular subtypes in Saudi women.}, journal = {Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society}, volume = {29}, number = {6}, pages = {609-615}, pmid = {34194268}, issn = {1319-0164}, abstract = {BACKGROUND/INTRODUCTION: Despite advances in the diagnosis and management of breast cancer (BC), it is still associated with high mortality rates. New biomarkers are being developed for the diagnosis, treatment, and prediction of responses of BC. Ceramide (CER), a bioactive sphingolipid, has emerged recently as a useful diagnostic tool in several types of tumors. In this study, we evaluated CER expression in invasive BC and assessed its relation to the molecular subtypes of BC.

MATERIALS AND METHODS: The clinical data and histopathological slides of 50 patients with invasive ductal carcinoma were retrieved and reviewed. The cases were then stained with a mouse monoclonal anti-ceramide antibody. Pearson correlation was used to assess the correlation between CER percentage and intensity and other clinical and pathological variables.

RESULTS: CER expression showed a direct relationship with estrogen and progesterone receptors Allred scores. However, it showed an inverse relation with tumor grade, HER2/neu status and Ki-67 index.

CONCLUSIONS: CER expression is likely to be associated with luminal BC molecular subtypes. However, more research is needed to confirm these results and to explore its relation to the different clinical outcomes, including response to treatment and prognosis.}, } @article {pmid34190628, year = {2022}, author = {Badjatia, N and Haymore, J and Voorhees, ME and Goundry, K and Lewis, C and Judd, G and Sanchez, S}, title = {Development of a Resting Energy Expenditure Estimation in Patients Undergoing Targeted Temperature Management with a Surface Gel Pad Temperature Modulating Device.}, journal = {Therapeutic hypothermia and temperature management}, volume = {12}, number = {1}, pages = {38-42}, doi = {10.1089/ther.2021.0005}, pmid = {34190628}, issn = {2153-7933}, mesh = {Calorimetry, Indirect ; Energy Metabolism ; Female ; Humans ; *Hypothermia, Induced ; Male ; Middle Aged ; Shivering ; Temperature ; }, abstract = {Targeted temperature management (TTM) directly impacts energy expenditure via temperature modulation and shivering associated with temperature modulating devices. We hypothesized that resting energy expenditure (REE) can be accurately estimated utilizing data obtained from a surface gel pad temperature modulating device (TMD) and demographic factors. Baseline demographic data, along with concurrent temperature, sedation, and shivering data, and indirect calorimetry (IDC) were collected from patients undergoing TTM. The data from the IDC and temperature modulation device (TMD) were synchronized and averaged over 60-second intervals to provide simultaneous comparisons. Heat transfer (calories) was calculated from the TMD by an equation that assessed water temperature from the TMD to the patient, water temperature returning to the TMD, water flow rates, and device mode. A linear regression model was used to determine factors associated with REE as measured by IDC. A difference in the mean between REE and estimated REE was used to assess accuracy. There were 48 assessments conducted in 40 subjects [mean (standard deviation)] age: 58 (14) years, 60% female, body surface area (BSA): 2.0 ± 0.3 who underwent simultaneous assessments. Target temperature was 36-37°C in 75%, with a median Bedside Shivering Assessment Score of 0 (range 0-2). Factors associated with REE on multivariable linear regression included older age (p < 0.001), male sex (p = 0.004), higher BSA (p < 0.001), higher patient temperature (p < 0.001), and lower heat transfer (p = 0.003). Adjusted prediction coefficients from this model were then tested against REE by a Bland-Altman analysis. The difference between difference in resting energy estimation (REEdiff) and measured REE by IDC was 6.2 calories/min (REEdiff: 95% confidence interval: -14.1 calories, 26.5 calories, p = 0.5). We believe that the heat transfer data from the TMD coupled with clinical characteristics of patients can be utilized to calculate the REE for every minute of TTM. These data can be utilized to mitigate the consequences of shivering and malnutrition during TTM.}, } @article {pmid34189474, year = {2021}, author = {Greulich, F and Mechtidou, A and Horn, T and Uhlenhaut, NH}, title = {Protocol for using heterologous spike-ins to normalize for technical variation in chromatin immunoprecipitation.}, journal = {STAR protocols}, volume = {2}, number = {3}, pages = {100609}, pmid = {34189474}, issn = {2666-1667}, mesh = {Animals ; Binding Sites ; Chromatin Immunoprecipitation/*methods ; Drosophila melanogaster ; High-Throughput Nucleotide Sequencing/methods ; Mice ; Proteins/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {Quantifying differential genome occupancy by chromatin immunoprecipitation (ChIP) remains challenging due to variation in chromatin fragmentation, immunoprecipitation efficiencies, and intertube variability. In this protocol, we add heterologous spike-ins from Drosophila chromatin as an internal control to the mice chromatin before immunoprecipitation to normalize for technical variation in ChIP-qPCR or ChIP-seq. The choice of spike-in depends on the evolutionary conservation of the protein of interest and the antibody used. For complete details on the use and execution of this protocol, please refer to Greulich et al. (2021).}, } @article {pmid34188137, year = {2021}, author = {Mayopoulos, GA and Ein-Dor, T and Li, KG and Chan, SJ and Dekel, S}, title = {COVID-19 positivity associated with traumatic stress response to childbirth and no visitors and infant separation in the hospital.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13535}, pmid = {34188137}, issn = {2045-2322}, support = {R21 HD100817/HD/NICHD NIH HHS/United States ; R21HD100817//National Institute of Child Health and Human Development/ ; }, mesh = {Adult ; Anxiety/diagnosis ; Birth Weight ; COVID-19/diagnosis/*psychology/virology ; Female ; Hospitals ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Pain/pathology ; Parturition/*psychology ; Patient Admission/statistics & numerical data ; Pregnancy ; Pregnant Women/*psychology ; SARS-CoV-2/isolation & purification ; Stress Disorders, Post-Traumatic/*diagnosis ; Stress, Psychological ; Surveys and Questionnaires ; }, abstract = {As the novel coronavirus (COVID-19) has spread globally, a significant portion of pregnant and delivering women were infected with COVID-19. While emerging studies examined birth outcomes in COVID-19 positive women, knowledge of the psychological experience of childbirth and maternal wellness remains lacking. This matched-control survey-based study included a sample of women recruited during the first wave of the pandemic in the US who gave birth in the previous six months. Women reporting confirmed/suspected COVID-19 (n = 68) during pregnancy or childbirth were matched on background factors with women reporting COVID-19 negativity (n = 2,276). We found nearly 50% of COVID positive women endorsed acute traumatic stress symptoms at a clinical level in response to childbirth. This group was more than twice as likely to endorse acute stress and to have no visitors during maternity hospitalization than COVID negative women; they were also less likely to room-in with newborns. The COVID positive group reported higher levels of pain in delivery, lower newborn weights, and more infant admission to neonatal intensive care units. Our findings suggest COVID-19 affected populations are at increased risk for traumatic childbirth and associated risk for psychiatric morbidity. Attention to delivering women's wellbeing is warranted during the pandemic.}, } @article {pmid34187216, year = {2021}, author = {Danzinger, S and Hielscher, N and Izsó, M and Metzler, J and Trinkl, C and Pfeifer, C and Tendl-Schulz, K and Singer, CF}, title = {Invasive lobular carcinoma: clinicopathological features and subtypes.}, journal = {The Journal of international medical research}, volume = {49}, number = {6}, pages = {3000605211017039}, pmid = {34187216}, issn = {1473-2300}, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Lobular/surgery ; Female ; Humans ; Retrospective Studies ; }, abstract = {OBJECTIVE: To analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors.

METHODS: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC).

RESULTS: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (+), have a lower proliferation rate (Ki67 <14%), and a higher pathological T stage (pT2-4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ER+, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1-3) was significantly more frequent with ILC versus IDC.

CONCLUSIONS: Our data suggest that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.}, } @article {pmid34185954, year = {2022}, author = {Zhao, J and Sun, G and Zhu, S and Dai, J and Chen, J and Zhang, M and Ni, Y and Zhang, H and Shen, P and Zhao, X and Zhang, B and Pan, X and Nie, L and Yin, X and Liang, J and Zhang, X and Wang, Z and Zhu, X and Liao, B and Liu, Z and Armstrong, CM and Gao, AC and Huang, H and Chen, N and Zeng, H}, title = {Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.}, journal = {BJU international}, volume = {129}, number = {3}, pages = {345-355}, doi = {10.1111/bju.15530}, pmid = {34185954}, issn = {1464-410X}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Circulating Tumor DNA/genetics ; Humans ; Male ; Phenotype ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; }, abstract = {OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P).

PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.

RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036).

CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.}, } @article {pmid34185678, year = {2021}, author = {Fedorov, A and Longabaugh, WJR and Pot, D and Clunie, DA and Pieper, S and Aerts, HJWL and Homeyer, A and Lewis, R and Akbarzadeh, A and Bontempi, D and Clifford, W and Herrmann, MD and Höfener, H and Octaviano, I and Osborne, C and Paquette, S and Petts, J and Punzo, D and Reyes, M and Schacherer, DP and Tian, M and White, G and Ziegler, E and Shmulevich, I and Pihl, T and Wagner, U and Farahani, K and Kikinis, R}, title = {NCI Imaging Data Commons.}, journal = {Cancer research}, volume = {81}, number = {16}, pages = {4188-4193}, pmid = {34185678}, issn = {1538-7445}, support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201000031C/CA/NCI NIH HHS/United States ; HHSN261201500001C/CA/NCI NIH HHS/United States ; HHSN261201500001G/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; P41 EB028741/EB/NIBIB NIH HHS/United States ; HHSN261201500001W/CA/NCI NIH HHS/United States ; }, mesh = {Biomedical Research/trends ; Cloud Computing ; Computational Biology/methods ; Computer Graphics ; Computer Security ; Data Interpretation, Statistical ; Databases, Factual ; Diagnostic Imaging/*methods/standards ; Humans ; Image Processing, Computer-Assisted ; *National Cancer Institute (U.S.) ; Neoplasms/*diagnostic imaging/*genetics ; Pilot Projects ; Programming Languages ; Radiology/methods/standards ; Reproducibility of Results ; Software ; United States ; User-Computer Interface ; }, abstract = {The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) aims to establish a national cloud-based data science infrastructure. Imaging Data Commons (IDC) is a new component of CRDC supported by the Cancer Moonshot. The goal of IDC is to enable a broad spectrum of cancer researchers, with and without imaging expertise, to easily access and explore the value of deidentified imaging data and to support integrated analyses with nonimaging data. We achieve this goal by colocating versatile imaging collections with cloud-based computing resources and data exploration, visualization, and analysis tools. The IDC pilot was released in October 2020 and is being continuously populated with radiology and histopathology collections. IDC provides access to curated imaging collections, accompanied by documentation, a user forum, and a growing number of analysis use cases that aim to demonstrate the value of a data commons framework applied to cancer imaging research. SIGNIFICANCE: This study introduces NCI Imaging Data Commons, a new repository of the NCI Cancer Research Data Commons, which will support cancer imaging research on the cloud.}, } @article {pmid34181649, year = {2021}, author = {Aftab, F and Ahmed, I and Ahmed, S and Ali, SM and Amenga-Etego, S and Ariff, S and Bahl, R and Baqui, AH and Begum, N and Bhutta, ZA and Biemba, G and Cousens, S and Das, V and Deb, S and Dhingra, U and Dutta, A and Edmond, K and Esamai, F and Ghosh, AK and Gisore, P and Grogan, C and Hamer, DH and Herlihy, J and Hurt, L and Ilyas, M and Jehan, F and Juma, MH and Kalonji, M and Khanam, R and Kirkwood, BR and Kumar, A and Kumar, A and Kumar, V and Manu, A and Marete, I and Mehmood, U and Minckas, N and Mishra, S and Mitra, DK and Moin, MI and Muhammad, K and Newton, S and Ngaima, S and Nguwo, A and Nisar, MI and Otomba, J and Quaiyum, MA and Sarrassat, S and Sazawal, S and Semrau, KE and Shannon, C and Singh, VP and Soofi, S and Soremekun, S and Suleiman, AM and Sunday, V and Dilip, TR and Tshefu, A and Wasan, Y and Yeboah-Antwi, K and Yoshida, S and Zaidi, AK and , }, title = {Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.}, journal = {PLoS medicine}, volume = {18}, number = {6}, pages = {e1003644}, pmid = {34181649}, issn = {1549-1676}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adolescent ; Adult ; Africa South of the Sahara/epidemiology ; Asia/epidemiology ; Female ; Humans ; Infant ; *Infant Mortality ; Infant, Newborn ; *Maternal Mortality ; Pregnancy ; Pregnancy Complications/diagnosis/*mortality ; Pregnancy Outcome ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stillbirth/*epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.

METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.

CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.

TRIAL REGISTRATION: The study is not a clinical trial.}, } @article {pmid34180691, year = {2021}, author = {Zilcha-Mano, S and Dolev-Amit, T and Fisher, H and Ein-Dor, T and Strauß, B}, title = {Patients' individual differences in implicit and explicit expectations from the therapist as a function of attachment orientation.}, journal = {Journal of counseling psychology}, volume = {68}, number = {6}, pages = {682-695}, doi = {10.1037/cou0000503}, pmid = {34180691}, issn = {0022-0167}, support = {//Israeli Science Foundation/ ; }, mesh = {Anxiety ; Anxiety Disorders ; Humans ; *Individuality ; *Motivation ; Object Attachment ; Professional-Patient Relations ; Psychotherapy ; }, abstract = {Patients' attachment orientation was found to be an important predictor of the process and outcome of psychotherapy. The present study is the first to examine whether patients' attachment orientation toward significant others predicts their implicit and explicit expectations from the therapist, and whether this effect is moderated by the extent to which the therapist has become an attachment figure. In two studies (N = 308), we developed measures of implicit (lexical decision task) and explicit expectations from therapist, and tested the presence of individual differences in expectations as a function of the patients' attachment orientation, early and late in treatment. Whereas individuals higher on attachment anxiety did not report having fewer positive expectations from therapist early in treatment, they showed lower accessibility of positive expectations when measured implicitly. As treatment progressed, the extent to which the therapist has become an attachment figure may mitigate the adverse effects of pretreatment attachment anxiety. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid34180038, year = {2021}, author = {Uomori, T and Horimoto, Y and Takanashi, M and Shikanai, A and Nakai, K and Arakawa, A and Saito, M}, title = {Cerebral hemorrhage due to amyloid angiopathy that was difficult to differentiate from breast cancer metastasis: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {150}, pmid = {34180038}, issn = {2198-7793}, abstract = {BACKGROUND: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient's cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA.

CASE PRESENTATION: A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells.

CONCLUSION: Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.}, } @article {pmid34177779, year = {2021}, author = {Picillo, M and Ricciardi, C and Tepedino, MF and Abate, F and Cuoco, S and Carotenuto, I and Erro, R and Ricciardelli, G and Russo, M and Cesarelli, M and Barone, P and Amboni, M}, title = {Gait Analysis in Progressive Supranuclear Palsy Phenotypes.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {674495}, pmid = {34177779}, issn = {1664-2295}, abstract = {The objective of the present study was to describe gait parameters of progressive supranuclear palsy (PSP) phenotypes at early stage verifying the ability of gait analysis in discriminating between disease phenotypes and between the other variant syndromes of PSP (vPSP) and Parkinson's disease (PD). Nineteen PSP (10 PSP-Richardson's syndrome, five PSP-parkinsonism, and four PSP-progressive gait freezing) and nine PD patients performed gait analysis in single and dual tasks. Although phenotypes showed similar demographic and clinical variables, Richardson's syndrome presented worse cognitive functions. Gait analysis demonstrated worse parameters in Richardson's syndrome compared with the vPSP. The overall diagnostic accuracy of the statistical model during dual task was almost 90%. The correlation analysis showed a significant relationship between gait parameters and visuo-spatial, praxic, and attention abilities in PSP-Richardson's syndrome only. vPSP presented worse gait parameters than PD. Richardson's syndrome presents greater gait dynamic instability since the earliest stages than other phenotypes. Computerized gait analysis can differentiate between PSP phenotypes and between vPSP and PD.}, } @article {pmid34177448, year = {2021}, author = {Baharav, S and Nitsan, G and Ben-David, BM}, title = {Commentary: Working Memory Load Affects Processing Time in Spoken Word Recognition: Test Retest Reliability of the E-WINDMIL Eyetracking Paradigm.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {663930}, pmid = {34177448}, issn = {1662-4548}, } @article {pmid34169195, year = {2021}, author = {March, DS and Hurt, AW and Grantham, CE and Churchward, DR and Young, HML and Highton, PJ and Dungey, M and Bishop, NC and Smith, AC and Graham-Brown, MPM and Cooper, NJ and Burton, JO}, title = {A Cost-Effective Analysis of the CYCLE-HD Randomized Controlled Trial.}, journal = {Kidney international reports}, volume = {6}, number = {6}, pages = {1548-1557}, pmid = {34169195}, issn = {2468-0249}, abstract = {INTRODUCTION: No formal cost-effectiveness analysis has been performed for programs of cycling exercise during dialysis (intradialytic cycling [IDC]). The objective of this analysis is to determine the effect of a 6-month program of IDC on health care costs.

METHODS: This is a retrospective formal cost-effectiveness analysis of adult participants with end-stage kidney disease undertaking in-center maintenance hemodialysis enrolled in the CYCLE-HD trial. Data on hospital utilization, primary care consultations, and prescribed medications were extracted from medical records for the 6 months before, during, and after a 6-month program of thrice-weekly IDC. The cost-effectiveness analysis was conducted from a health care service perspective and included the cost of implementing the IDC intervention. The base-case analyses included a 6-month "within trial" analysis and a 12-month "within and posttrial" analysis considering health care utilization and quality of life (QoL) outcomes.

RESULTS: Data from the base-case within trial analysis, based on 109 participants (n = 56 control subjects and n = 53 IDC subjects) showed a reduction in health care utilization costs between groups, favoring the IDC group, and a 73% chance of IDC being cost-effective compared with control subjects at a willingness to pay of £20,000 and £30,000 per quality-adjusted life year (QALY) gained. When QoL data points were extrapolated forward to 12 months, the probability of IDC being cost-effective was 93% and 94% at £20,000 and £30,000 per QALY gained. Sensitivity analysis broadly confirms these findings.

CONCLUSION: A 6-month program of IDC is cost-effective and the implementation of these programs nationally should be a priority.}, } @article {pmid34167092, year = {2021}, author = {Zhou, J and He, Y and Wang, Y and Li, X and Xu, C}, title = {Metal-free N and O Co-doped carbon directly derived from bicrystal Zn-based zeolite-like metal-organic frameworks as durable high-performance pH-universal oxygen reduction reaction catalyst.}, journal = {Nanotechnology}, volume = {32}, number = {40}, pages = {}, doi = {10.1088/1361-6528/ac0e6a}, pmid = {34167092}, issn = {1361-6528}, abstract = {A simple and green approach is studied for the preparation of a high-activity metal-free N,O-codoped porous carbon (NOPC) electrocatalyst by one-step pyrolysis of pristine zinc-based zeolite-like metal-organic framework (Zn-ZMOF) synthesized by hydrothermal method from Zn[2+]and 4,5-imidazoledicarboxylic acid (H3IDC) in H2O solvent. It is found that the structure and electroactivity of Zn-ZMOF and NOPC vary with the molar ratio of H3IDC to zinc acetate. NOPC shows pH-universal electrocatalytic property for oxygen reduction reaction and its electrocatalytic performance is similar to that of Pt/C in alkaline and neutral electrolytes, and is close to that of Pt/C in acidic electrolyte, which is a relatively rare case for metal-free porous carbon derived from pristine MOF. Meanwhile, NOPC displays higher long-term stability and better tolerance to methanol and carbon monoxide poisoning than that of commercial Pt/C. The excellent performance of NOPC is mainly due to the special structure of the precursor Zn-ZMOF, and the synergism of abundant active sites, micro/mesoporous structure, large specific surface area, and high degree of graphitization.}, } @article {pmid34166430, year = {2021}, author = {Nkadimeng, MV and Makombe, G and Mapiye, O and Mapiye, C and Oluwatayo, I and Dzama, K and Mojapelo, C and Mollel, N and Ngambi, J and Mautjana, MH}, title = {A gross margin analysis for Nguni cattle farmers in Limpopo Province, South Africa.}, journal = {PloS one}, volume = {16}, number = {6}, pages = {e0253657}, pmid = {34166430}, issn = {1932-6203}, mesh = {Animal Husbandry/*economics ; Animals ; Cattle ; *Farmers ; Farms/*economics ; Humans ; South Africa ; }, abstract = {Factors such as increases in population, urbanization, growth in per capita income and changes in consumer taste and preferences are causing gradual increases in livestock product consumption and demand. South Africa is addressing this predicted increase in livestock products demand by commercializing smallholder livestock producers. The Limpopo Industrial Development Corporation (IDC) Nguni Cattle Development Project is an example of such effort. The economic performance of these efforts needs to be evaluated. We use gross margin analysis to evaluate the performance of the Limpopo IDC Nguni Cattle Development Project. Additionally, we use regression analysis to identify factors influencing gross margins. Our results indicate that although smallholders show potential to commercialize, they lack commercial farming experience and require that a strong extension support system be used as one of the strategies to improve profitability. We also noted that individual farmers were more profitable than group farmers. Multiple regression analysis shows that three variables could be used to stimulate gross margin among the Limpopo IDC Nguni Cattle Development Project farmers. These are herd size, distance to market and farm size. Since farm size is a given, policy should focus on assisting farmers to build their herds and to have better access to markets.}, } @article {pmid34154844, year = {2021}, author = {Sugie, M and Takahara, T and Ohashi, A and Sassa, N and Tsuzuki, T}, title = {Presence of corpora amylacea among prostate cancer cells: an unrecognised feature of intraductal carcinoma of the prostate.}, journal = {Pathology}, volume = {53}, number = {5}, pages = {574-578}, doi = {10.1016/j.pathol.2020.09.033}, pmid = {34154844}, issn = {1465-3931}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Humans ; Hyalin ; Inclusion Bodies/pathology ; Male ; Middle Aged ; Neoplasm Grading ; Prostate/pathology ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; }, abstract = {Corpora amylacea (CA) is usually present in benign prostatic ducts and acini, and its presence is considered suggestive of negative or low-risk prostate cancer. The clinicopathological definition of CA among prostate cancer cells (CAPCCs)-described as CA entirely surrounded by invasive cancer cells-has not been discussed. As intraductal carcinoma of the prostate (IDC-P) is a well-known adverse prognostic factor in prostate cancer, this study aimed to elucidate the relationship between CAPCC and IDC-P. We enrolled 366 patients who underwent robotic-assisted radical prostatectomies between 2012 and 2018 at Aichi Medical University Hospital. All surgical specimens were independently reviewed by two genitourinary pathologists. The median age of the patients was 68.5 years; the median serum prostate-specific antigen was 6.49 ng/mL. IDC-P was observed in 143 (39.1%) patients, while the presence of CAPCC was observed in 47 cases (12.8%). Patients with CAPCC were associated with more advanced clinical and pathological T stages, as well as Gleason scores, than those without CAPCC (p=0.018, p<0.001, p=0.036). Notably, the presence of CAPCC was significantly associated with the presence of IDC-P (39 cases) and a high Gleason score compared with the absence of CAPCC (12 cases) (p<0.001 and p=0.036, respectively). The presence of CAPCC is an adverse pathological feature, often closely related to IDC-P. Therefore, CAPCC may be a surrogate finding to detect IDC-P via haematoxylin and eosin staining.}, } @article {pmid34153806, year = {2021}, author = {Gandolfi, M and Fiorio, M and Geroin, C and Prior, M and De Marchi, S and Amboni, M and Smania, N and Tinazzi, M}, title = {Motor dual task with eyes closed improves postural control in patients with functional motor disorders: A posturographic study.}, journal = {Gait & posture}, volume = {88}, number = {}, pages = {286-291}, doi = {10.1016/j.gaitpost.2021.06.011}, pmid = {34153806}, issn = {1879-2219}, mesh = {Accidental Falls ; Adult ; Attention ; Cognition ; Humans ; Middle Aged ; *Motor Disorders ; *Postural Balance ; Young Adult ; }, abstract = {BACKGROUND: Functional motor disorders (FMD) are highly disabling neurological conditions in which postural control deficits increase the risk of falls and disability in performing daily living activities. Scattered evidence suggests that such disturbances may depend on abnormal attentional focus and might improve with distraction.

RESEARCH QUESTION: How do motor and cognitive dual tasks performed under two different sensory conditions shape postural control in patients with FMD.

METHODS: This posturographic study involved 30 patients with FMD (age, 45.20 ± 14.57 years) and 30 healthy controls (age, 41.20 ± 16.50 years). Postural parameters were measured with eyes open, and eyes closed in quiet stance (single task) and on a motor dual task (m-DT) and a calculation (cognitive) dual task (c-DT). The dual task effect (DTE, expressed in percentage) on motor and cognitive performance was calculated for sway area, length of Center of Pressure (CoP), and velocity of CoP displacement.

RESULTS: There was a statistically significant three-way interaction between task, condition, and group for the DTE on sway area (p = 0.03). The mean sway area DTE on the motor task in the eyes-closed condition was increased by 70.4 % in the healthy controls, while it was decreased by 1% in the patient group (p = 0.003). No significant three-way interaction was observed for the DTE on length of CoP and velocity of CoP displacement.

SIGNIFICANCE: This study provides novel preliminary evidence for the benefit of a simple motor dual task in the eyes closed condition as a way to improve postural control in patients with FMD. These findings are relevant for the management of postural control disorders in patients with FMD.}, } @article {pmid34152024, year = {2021}, author = {DeCoste, RC and Carter, MD and Barnes, PJ and Andea, AA and Wang, M and Rayson, D and Walsh, NM}, title = {Independent primary cutaneous and mammary apocrine carcinomas with neuroendocrine differentiation: Report of a case and literature review.}, journal = {Journal of cutaneous pathology}, volume = {48}, number = {11}, pages = {1397-1403}, doi = {10.1111/cup.14085}, pmid = {34152024}, issn = {1600-0560}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Skin Appendage/*pathology ; Female ; Humans ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; }, abstract = {Cutaneous apocrine carcinomas share common features with their counterparts in the breast; hence, metastatic mammary carcinoma must be excluded before such lesions can be designated primary cutaneous neoplasms. Primary tumors from either source rarely exhibit neuroendocrine differentiation. We report a case of a 72-year-old female with a painless 1.2-cm scalp nodule. An incisional biopsy revealed dermal involvement by an invasive apocrine carcinoma juxtaposed to a benign apocrine cystic lesion. Immunohistochemically, the carcinoma expressed neuroendocrine proteins including synaptophysin, chromogranin, and CD56. A primary cutaneous apocrine carcinoma with neuroendocrine differentiation was favored, but additional investigations to exclude breast origin were recommended. These revealed a 1.1-cm nodule in the right breast, which proved to be an invasive ductal carcinoma, morphologically and immunophenotypically similar to the scalp lesion. This confounded the case, yet factors militating against metastatic breast carcinoma to skin included (a) the small size of the mammary tumor, (b) absence of other metastatic disease, and (c) juxtaposition of the scalp carcinoma to a putative benign precursor. Molecular studies were undertaken to resolve the diagnostic quandary. Single nucleotide polymorphism microarray analysis revealed distinct patterns of chromosomal copy number alterations in the two tumors, supporting the concept of synchronous and unusual primary neoplasms.}, } @article {pmid34150374, year = {2021}, author = {Munawar, S and Haider, R and Ali, SM and Yaqeen, SR and Islam, S and Asghar, IA and Afzal, A and Zia, S and Irfan, M and Hashmi, AA}, title = {Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome.}, journal = {Cureus}, volume = {13}, number = {5}, pages = {e15006}, pmid = {34150374}, issn = {2168-8184}, abstract = {Introduction Metaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. Methods We conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. Results The mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. Conclusion We found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.}, } @article {pmid34147428, year = {2021}, author = {Abascal-Junquera, JM and Fumadó-Ciutat, L and Gasa-Galmes, B and Costa-Planells, M and Munarriz-Polo, M and Sanromà-Salvà, A and Polaina-Barroso, L and Solà-Marqués, C and Juanpere-Rodero, N and Lloreta-Trull, J and Cecchini-Rosell, L}, title = {Concomitant intraductal carcinoma of the prostate and response to hormonal therapy in metastatic prostate carcinoma.}, journal = {Actas urologicas espanolas}, volume = {45}, number = {6}, pages = {455-460}, doi = {10.1016/j.acuroe.2020.06.004}, pmid = {34147428}, issn = {2173-5786}, mesh = {*Carcinoma, Intraductal, Noninfiltrating ; Humans ; Male ; Phenylthiohydantoin ; *Prostatic Neoplasms, Castration-Resistant/drug therapy ; Retrospective Studies ; }, abstract = {INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.

PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.

RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (P = .007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (P = .05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (P = .001). In the multivariate analysis, adenocarcinoma subtype was statistically significant P .014, CI 95% (HR 0.058, 0.006-0.56) CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. Once IDC-P is identified, clinicians could extrapolate the relative poor response to hormonal therapy. Consequently, follow-up of these patients in this scenario should be more strict.}, } @article {pmid34142156, year = {2021}, author = {Nakamura, T and Okabe, K and Hirayama, S and Chirifu, M and Ikemizu, S and Morioka, H and Nakabeppu, Y and Yamagata, Y}, title = {Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.}, journal = {Nucleic acids research}, volume = {49}, number = {12}, pages = {7154-7163}, pmid = {34142156}, issn = {1362-4962}, mesh = {Adenine ; Adenomatous Polyposis Coli/genetics ; Amino Acid Motifs ; Animals ; DNA/chemistry ; DNA Glycosylases/*chemistry/genetics ; DNA Repair ; DNA Replication ; Guanine/analogs & derivatives ; Humans ; Mice ; Models, Molecular ; Mutation ; Proliferating Cell Nuclear Antigen/chemistry ; Zinc ; }, abstract = {Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9-Rad1-Hus1 complex (9-1-1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9-1-1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.}, } @article {pmid34133649, year = {2021}, author = {Rocha, SR and Marques, CAV}, title = {Functional capacity of women with breast neoplasm undergoing palliative chemotherapy.}, journal = {Revista da Escola de Enfermagem da U S P}, volume = {55}, number = {}, pages = {e03714}, doi = {10.1590/S1980-220X2020006303714}, pmid = {34133649}, issn = {1980-220X}, mesh = {*Breast Neoplasms/drug therapy ; Cross-Sectional Studies ; Female ; Humans ; *Palliative Care ; }, abstract = {OBJECTIVE: To evaluate the functional capacity of women with breast neoplasm undergoing palliative chemotherapy.

METHOD: Cross-sectional study with an analysis of medical records of women with breast cancer undergoing palliative chemotherapy.

RESULTS: Out of one hundred evaluated records, most registered 50 years or older (66%), primary education (53%), an income of 1 to 2 minimum wages (87%), invasive ductal carcinoma (95%), positive hormone receptor (64%), and histological grade 1 and 2 (57%). Performance status 0 (49%), 1 (39%), and 2 (12%) were prevalent; these imply, respectively, active patients, with mild and moderate activity restriction. One to four chemotherapy schemes were associated with the inappetence (p =0.00) and weight loss (p =0.001) symptoms. The main complications were neuropathy (31%), medullary compression syndrome (21%), neutropenia (9%), and death (28%).

CONCLUSION: Out of the analyzed women, 88% presented functional capacity 0 and 1, had no or mild restriction of daily activities, were multiply treated, and manifested manageable symptoms. Others, however, presented moderate to severe clinical complications during the treatment, progressing to exclusive palliative care or death.}, } @article {pmid34133406, year = {2021}, author = {Akhavan, AA and Wirtz, EC and Ollila, DW and Bhatt, N}, title = {An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.}, journal = {Plastic and reconstructive surgery}, volume = {148}, number = {2}, pages = {299-303}, doi = {10.1097/PRS.0000000000008155}, pmid = {34133406}, issn = {1529-4242}, mesh = {Adalimumab/*adverse effects ; Breast Implantation/*adverse effects/instrumentation ; Breast Implants/*adverse effects ; Breast Neoplasms/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant/adverse effects/methods ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/etiology/surgery ; Mastectomy/adverse effects ; Middle Aged ; Surface Properties ; Tissue Expansion Devices/*adverse effects ; }, abstract = {Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.}, } @article {pmid34132930, year = {2022}, author = {Rachamim, L and Nacasch, N and Sinay, I}, title = {Complicated Grief, Depression, Health and Attachment Style in First Degree Relatives of Individuals with a Chronic Psychotic Disorders.}, journal = {Community mental health journal}, volume = {58}, number = {3}, pages = {526-535}, pmid = {34132930}, issn = {1573-2789}, mesh = {Adult ; Humans ; Depression/epidemiology ; Grief ; *Mental Disorders/epidemiology ; Prevalence ; *Psychotic Disorders/epidemiology ; Adult Children ; }, abstract = {Complicated grief (CG) is a form of unrelenting grief after the death of a loved one. However, family members of individuals who suffer from Schizophrenia, Schizoaffective disorders and Bipolar disorder may experience symptoms of CG even though their loved one is still alive. The present study assessed CG and risk factors for CG in first degree relatives of individuals with severe chronic mental illness. The incidence of CG was examined in 78 parents, siblings, adult children and spouses recruited through organizations and social media that provide support services for individuals suffering from mental illness and their families. High rates of CG (39.7%) were found in this group. CG was associated with a higher prevalence of posttraumatic and depression symptoms and poorer physical health. These findings may contribute to heightening therapists' awareness of the importance of assessing, acknowledging and resolving CG in the family members of patients with chronic psychotic disorders.}, } @article {pmid34131793, year = {2021}, author = {Roth, CJ and Clunie, DA and Vining, DJ and Berkowitz, SJ and Berlin, A and Bissonnette, JP and Clark, SD and Cornish, TC and Eid, M and Gaskin, CM and Goel, AK and Jacobs, GC and Kwan, D and Luviano, DM and McBee, MP and Miller, K and Hafiz, AM and Obcemea, C and Parwani, AV and Rotemberg, V and Silver, EL and Storm, ES and Tcheng, JE and Thullner, KS and Folio, LR}, title = {Multispecialty Enterprise Imaging Workgroup Consensus on Interactive Multimedia Reporting Current State and Road to the Future: HIMSS-SIIM Collaborative White Paper.}, journal = {Journal of digital imaging}, volume = {34}, number = {3}, pages = {495-522}, pmid = {34131793}, issn = {1618-727X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Consensus ; Diagnostic Imaging ; Humans ; Multimedia ; *Radiology ; *Radiology Information Systems ; }, abstract = {Diagnostic and evidential static image, video clip, and sound multimedia are captured during routine clinical care in cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, endoscopic procedural specialties, and other medical disciplines. Providers typically describe the multimedia findings in contemporaneous electronic health record clinical notes or associate a textual interpretative report. Visual communication aids commonly used to connect, synthesize, and supplement multimedia and descriptive text outside medicine remain technically challenging to integrate into patient care. Such beneficial interactive elements may include hyperlinks between text, multimedia elements, alphanumeric and geometric annotations, tables, graphs, timelines, diagrams, anatomic maps, and hyperlinks to external educational references that patients or provider consumers may find valuable. This HIMSS-SIIM Enterprise Imaging Community workgroup white paper outlines the current and desired clinical future state of interactive multimedia reporting (IMR). The workgroup adopted a consensus definition of IMR as "interactive medical documentation that combines clinical images, videos, sound, imaging metadata, and/or image annotations with text, typographic emphases, tables, graphs, event timelines, anatomic maps, hyperlinks, and/or educational resources to optimize communication between medical professionals, and between medical professionals and their patients." This white paper also serves as a precursor for future efforts toward solving technical issues impeding routine interactive multimedia report creation and ingestion into electronic health records.}, } @article {pmid34130539, year = {2021}, author = {Bai, Y and Tao, X and Xu, C and Zhu, Y}, title = {Diagnosis and treatment of chylous leakage after modified radical mastectomy for breast cancer: a case report.}, journal = {The Journal of international medical research}, volume = {49}, number = {6}, pages = {3000605211021375}, pmid = {34130539}, issn = {1473-2300}, mesh = {Axilla ; *Breast Neoplasms/surgery ; Female ; Humans ; Lymph Node Excision ; Mastectomy/adverse effects ; Mastectomy, Modified Radical ; Middle Aged ; }, abstract = {The post-operative complication of chylous leakage after breast cancer is relatively rare, and few clinical studies have been published. We report a 64-year-old woman with chylous leakage following modified radical mastectomy. We describe the patient's diagnostic and treatment process in detail. The patient was diagnosed with grade II (left) breast invasive ductal carcinoma. Post-operatively, the patient's chest wall and axilla were pressurized, and negative pressure drainage was initiated. On the fifth post-operative day, the drainage from the chest wall and axilla increased significantly, and the patient developed chylous leakage on the eighth postoperative day. We injected meglumine diatrizoate (100 mL) and elemene (10 mL) into the patient's axilla, and the chylous leakage gradually resolved 18 days post-operatively. In this report, we focus on managing a case of chylous leakage after modified radical mastectomy for breast cancer. Meglumine diatrizoate combined with elemene is a possible treatment for the management of this rare complication.}, } @article {pmid34127332, year = {2021}, author = {Kayadibi, Y and Ucar, N and Kaya, MF and Yildirim, E and Bektas, S}, title = {Characterization of Suspicious Microcalcifications on Mammography Using 2D Shear-Wave Elastography.}, journal = {Ultrasound in medicine & biology}, volume = {47}, number = {9}, pages = {2532-2542}, doi = {10.1016/j.ultrasmedbio.2021.05.008}, pmid = {34127332}, issn = {1879-291X}, mesh = {*Calcinosis/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating ; *Elasticity Imaging Techniques ; Humans ; Mammography ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {Our aim was to investigate the correlations between the findings of two-dimensional shear-wave elastography (2D-SWE) and the histopathologic results of microcalcifications (MCs) visualized using ultrasonography (USG). Fifty people with suspicious MCs without accompanying mass were evaluated. They underwent USG and 2D-SWE before USG-guided tru-cut biopsy. SWE values and histopathologic features were compared statistically. The variables between groups were analyzed using the Mann-Whitney U test. Receiver operating characteristic analysis was performed and cut-off values determined to discriminate malignancy, invasiveness and high grade. Pathology confirmed 27 malignant lesions (18 invasive ductal carcinomas, one invasive lobular and eight ductal carcinomas in situ) and 23 benign ones. There was a statistically significant difference between the SWE values of malignant and benign MCs (p < 0.001). The diagnostic performance of SWE for malignancy, invasiveness and high grade were as follows, repectively: sensitivity (93%, 83%, 88%), specificity (91%, 88%, 53%), positive predictive value (93%, 94%, 44%), negative predictive value (91%, 70%, 90%) and area under the curve (0.952, 0.885, 0.776). Cut-off values were determined as 57 kPa for malignancy, 124 kPa for invasiveness and 124.5 kPa for high grade. In conclusion, SWE is a useful method in clinical practice for characterizing MCs that can be visualized with USG.}, } @article {pmid34119440, year = {2021}, author = {Gnangnon, B and Duraisingh, MT and Buckee, CO}, title = {Deconstructing the parasite multiplication rate of Plasmodium falciparum.}, journal = {Trends in parasitology}, volume = {37}, number = {10}, pages = {922-932}, doi = {10.1016/j.pt.2021.05.001}, pmid = {34119440}, issn = {1471-5007}, mesh = {Animals ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Humans ; Malaria, Falciparum/parasitology ; *Plasmodium falciparum/growth & development ; *Protozoan Proteins/metabolism ; }, abstract = {Epidemiological indicators describing population-level malaria transmission dynamics are widely used to guide policy recommendations. However, the determinants of malaria outcomes within individuals are still poorly understood. This conceptual gap partly reflects the fact that there are few indicators that robustly predict the trajectory of individual infections or clinical outcomes. The parasite multiplication rate (PMR) is a widely used indicator for the Plasmodium intraerythrocytic development cycle (IDC), for example, but its relationship to clinical outcomes is complex. Here, we review its calculation and use in P. falciparum malaria research, as well as the parasite and host factors that impact it. We also provide examples of metrics that can help to link within-host dynamics to malaria clinical outcomes when used alongside the PMR.}, } @article {pmid34117742, year = {2021}, author = {Fortunato, A and Mallo, D and Rupp, SM and King, LM and Hardman, T and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC}, title = {A new method to accurately identify single nucleotide variants using small FFPE breast samples.}, journal = {Briefings in bioinformatics}, volume = {22}, number = {6}, pages = {}, pmid = {34117742}, issn = {1477-4054}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {*Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Computational Biology/*methods ; DNA, Neoplasm ; Female ; Genetic Heterogeneity ; Genetic Testing/methods/standards ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; *Polymorphism, Single Nucleotide ; Workflow ; }, abstract = {Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.}, } @article {pmid34103599, year = {2021}, author = {Bin Kanner, Y and Ganoth, A and Tsfadia, Y}, title = {Extracellular mutation induces an allosteric effect across the membrane and hampers the activity of MRP1 (ABCC1).}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12024}, pmid = {34103599}, issn = {2045-2322}, mesh = {Allosteric Regulation ; Amino Acid Substitution ; Humans ; Multidrug Resistance-Associated Proteins/*chemistry/*genetics ; *Mutation, Missense ; Protein Domains ; Protein Structure, Secondary ; }, abstract = {Dynamic conformational changes play a major role in the function of proteins, including the ATP-Binding Cassette (ABC) transporters. Multidrug Resistance Protein 1 (MRP1) is an ABC exporter that protects cells from toxic molecules. Overexpression of MRP1 has been shown to confer Multidrug Resistance (MDR), a phenomenon in which cancer cells are capable to defend themselves against a broad variety of drugs. In this study, we used varied computational techniques to explore the unique F583A mutation that is known to essentially lock the transporter in a low-affinity solute binding state. We demonstrate how macro-scale conformational changes affect MRP1's stability and dynamics, and how these changes correspond to micro-scale structural perturbations in helices 10-11 and the nucleotide-binding domains (NBDs) of the protein in regions known to be crucial for its ATPase activity. We demonstrate how a single substitution of an outward-facing aromatic amino acid causes a long-range allosteric effect that propagates across the membrane, ranging from the extracellular ECL5 loop to the cytoplasmic NBD2 over a distance of nearly 75 Å, leaving the protein in a non-functional state, and provide the putative allosteric pathway. The identified allosteric structural pathway is not only in agreement with experimental data but enhances our mechanical understanding of MRP1, thereby facilitating the rational design of chemosensitizers toward the success of chemotherapy treatments.}, } @article {pmid34101373, year = {2021}, author = {Icht, M and Zukerman, G and Ben-Itzchak, E and Ben-David, BM}, title = {Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta-analysis study.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1948-1964}, doi = {10.1002/aur.2551}, pmid = {34101373}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/complications ; Emotions ; Humans ; *Intellectual Disability/complications ; Language ; }, abstract = {Daily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) experience difficulties in identification of spoken emotions. We conducted a meta-analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer-reviewed journal articles) comparing individuals with ASD-without-ID (N = 614) and typically-developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF-ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD-without-ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new-look on emotion processing in ASD-without-ID. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions and target improved performance with complex emotions. LAY SUMMARY: Individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta-analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD-without-ID to process simple emotions.}, } @article {pmid34100170, year = {2021}, author = {Mahajan, K and Rojekar, S and Desai, D and Kulkarni, S and Bapat, G and Zinjarde, S and Vavia, P}, title = {Layer-by-Layer Assembled Nanostructured Lipid Carriers for CD-44 Receptor-Based Targeting in HIV-Infected Macrophages for Efficient HIV-1 Inhibition.}, journal = {AAPS PharmSciTech}, volume = {22}, number = {5}, pages = {171}, pmid = {34100170}, issn = {1530-9932}, mesh = {Alkynes/administration & dosage/chemical synthesis/metabolism ; Benzoxazines/administration & dosage/chemical synthesis/metabolism ; Cell Survival/drug effects/physiology ; Cyclopropanes/administration & dosage/chemical synthesis/metabolism ; Dose-Response Relationship, Drug ; Drug Carriers/*administration & dosage/chemical synthesis/metabolism ; Drug Delivery Systems/methods ; HEK293 Cells ; HIV Infections/drug therapy/metabolism ; HIV-1/*drug effects/physiology ; Humans ; *Hyaluronan Receptors/metabolism ; Lipids/administration & dosage/chemical synthesis ; Macrophages/*drug effects/metabolism ; Nanostructures/*administration & dosage/chemistry ; Reverse Transcriptase Inhibitors/*administration & dosage/chemical synthesis/metabolism ; THP-1 Cells ; }, abstract = {Macrophages act as a cellular reservoir in HIV infection. Elimination of HIV from macrophages has been an unfulfilled dream due to the failure of drugs to reach them. To address this, we developed CD44 receptor-targeted, novel hyaluronic acid (HA)-coated nanostructured lipid carriers (NLCs) of efavirenz via washless layer-by-layer (LbL) assembly of HA and polyallylamine hydrochloride (PAH). NLCs were subjected to TEM analysis, size and zeta potential, in vitro release and encapsulation efficiency studies. The uptake of NLCs in THP-1 cells was studied using fluorescence microscopy and flow cytometry. The anti-HIV efficacy was evaluated using p24 antigen inhibition assay. NLCs were found to be spherical in shape with anionic zeta potential (-23.66 ± 0.87 mV) and 241.83 ± 5.38 nm particle size. NLCs exhibited prolonged release of efavirenz during in vitro drug release studies. Flow cytometry revealed 1.73-fold higher uptake of HA-coated NLCs in THP-1 cells. Cytotoxicity studies showed no significant change in cell viability in presence of NLCs as compared with the control. HA-coated NLCs distributed throughout the cell including cytoplasm, plasma membrane and nucleus, as observed during fluorescence microscopy. HA-coated NLCs demonstrated consistent and significantly higher inhibition (81.26 ± 1.70%) of p24 antigen which was 2.08-fold higher than plain NLCs. The obtained results suggested preferential uptake of HA-coated NLCs via CD44-mediated uptake. The present finding demonstrates that HA-based CD44 receptor targeting in HIV infection is an attractive strategy for maximising the drug delivery to macrophages and achieve effective viral inhibition.}, } @article {pmid34099756, year = {2021}, author = {Netzer, O and Heimler, B and Shur, A and Behor, T and Amedi, A}, title = {Backward spatial perception can be augmented through a novel visual-to-auditory sensory substitution algorithm.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11944}, pmid = {34099756}, issn = {2045-2322}, mesh = {Adaptation, Physiological/physiology ; Adult ; *Algorithms ; Auditory Perception/*physiology ; Blindness/physiopathology ; Female ; Humans ; Male ; Psychomotor Performance/physiology ; Space Perception/*physiology ; Touch Perception/*physiology ; Visual Cortex/physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Can humans extend and augment their natural perceptions during adulthood? Here, we address this fascinating question by investigating the extent to which it is possible to successfully augment visual spatial perception to include the backward spatial field (a region where humans are naturally blind) via other sensory modalities (i.e., audition). We thus developed a sensory-substitution algorithm, the "Topo-Speech" which conveys identity of objects through language, and their exact locations via vocal-sound manipulations, namely two key features of visual spatial perception. Using two different groups of blindfolded sighted participants, we tested the efficacy of this algorithm to successfully convey location of objects in the forward or backward spatial fields following ~ 10 min of training. Results showed that blindfolded sighted adults successfully used the Topo-Speech to locate objects on a 3 × 3 grid either positioned in front of them (forward condition), or behind their back (backward condition). Crucially, performances in the two conditions were entirely comparable. This suggests that novel spatial sensory information conveyed via our existing sensory systems can be successfully encoded to extend/augment human perceptions. The implications of these results are discussed in relation to spatial perception, sensory augmentation and sensory rehabilitation.}, } @article {pmid34098822, year = {2021}, author = {Maitre, T and Ok, V and Calin, R and Lassel, L and Canestri, A and Denis, M and Hamidi, M and Tavolaro, S and Verdet, C and Parrot, A and Cadranel, J and Pialoux, G}, title = {Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.}, journal = {Therapeutic advances in respiratory disease}, volume = {15}, number = {}, pages = {17534666211003012}, pmid = {34098822}, issn = {1753-4666}, mesh = {Hospital Units ; Humans ; *Liver Abscess, Pyogenic/epidemiology/therapy ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.

METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.

RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05).

CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.}, } @article {pmid34098400, year = {2021}, author = {Busheri, L and Dixit, S and Nare, S and Alhat, R and Thomas, G and Jagtap, M and Navgire, R and Shinde, P and Banale, R and Unde, R and Reddy, R and Shaikh, S and Konnur, A and Namewar, N and Bapat, A and Patil, A and Johari, R and Kushwaha, R and Kumari, W and Varghese, B and Deshpande, P and Deshmukh, C and Kelkar, DA and Shashidhara, LS and Koppiker, CB and Kulkarni, M}, title = {Breast cancer biobank from a single institutional cohort in an urban setting in india: Tumor characteristics and survival outcomes.}, journal = {Cancer treatment and research communications}, volume = {28}, number = {}, pages = {100409}, doi = {10.1016/j.ctarc.2021.100409}, pmid = {34098400}, issn = {2468-2942}, mesh = {Breast Neoplasms/mortality ; Cohort Studies ; Female ; Humans ; India ; Middle Aged ; Survival Analysis ; Tissue Banks/*standards ; }, abstract = {BACKGROUND: A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines.

METHODS: The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank.

RESULTS: Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n = 799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years.

CONCLUSION: The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.}, } @article {pmid34097163, year = {2022}, author = {Joachim-Célestin, M and Chara, R and Montgomery, SB}, title = {Living Near an Immigration Detention Center: Impact on Latinas' Health.}, journal = {Journal of immigrant and minority health}, volume = {24}, number = {3}, pages = {626-638}, pmid = {34097163}, issn = {1557-1920}, support = {#2170480//Ardmore Foundation/ ; }, mesh = {Culture ; *Emigrants and Immigrants ; *Emigration and Immigration ; Hispanic or Latino ; Humans ; Jails ; }, abstract = {There is ample evidence that exposure to Immigration and Customs Enforcement (ICE) activities could widen Latinas' health disparities. Whether or not residing near an ICE detention center (IDC) further impacts their health is unknown. During nationwide increased ICE activities Latinas (N=45) attended an intervention at two separate sites: one near and another one far from an IDC. A focus group discussion and an interview were conducted using a grounded theory approach. Quantitative data were collected and analyzed. Participants residing near an IDC benefited less from the intervention and reported changes in anxiety levels and in mobility, and a sense of powerlessness. They also requested resources to respond to ICE overreach and broadcasting of their reality. Our results suggest that proximity to IDCs impacts immigrant communities and public health programming, which is inevitably embedded in political realities. These need to be addressed when providing much needed interventions.}, } @article {pmid34096509, year = {2021}, author = {Badak, B and Aykanat, NEB and Kacar, S and Sahinturk, V and Arik, D and Canaz, F}, title = {Effects of astaxanthin on metastasis suppressors in ductal carcinoma. A preliminary study.}, journal = {Annali italiani di chirurgia}, volume = {92}, number = {}, pages = {565-574}, pmid = {34096509}, issn = {2239-253X}, mesh = {*Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Neoplasm Metastasis ; Xanthophylls/pharmacology ; }, abstract = {BACKGROUND: Breast cancer (BC) is a major public health problem diagnosed in more than 2 million women worldwide in 2018, causing more than 600,000 deaths. 90% of deaths due to breast cancer are caused by metastasis. Metastasis is a complex process that is divided into several steps, including separation of tumor cells from the primary tumor, invasion, cell migration, intravasation, vasculature survival, extravasation, and colonization of the secondary site. Astaxanthin (AXT) is a marine-based ketocarotenoid that has many different potential functions such as anti-oxidant, anti-inflammatory and oxidative stress-reducing properties to potentially reduce the incidence of cancer or inhibit the expansion of tumor cells. This study aims to investigate the effects of astaxanthin as a new metastasis inhibitor on T47D human invasive ductal carcinoma breast cancer cell.

MATERIAL AND METHODS: To investigate the effects of the astaxanthin as a new metastasis inhibitor on T47D cell, expression levels of anti-maspin, anti-Kai1, anti-BRMS1, and anti-MKK4 were examined by western blot. Also, we evaluated differences of these suppressors expression levels in tissue sections of 10 patients diagnosed with in situ and invasive ductal carcinoma by immunohistochemistry method.

RESULT: 250 μM astaxanthin increased the activation of all metastasis suppressing proteins. Also, these metastasis suppressors showed higher expression in invasive ductal carcinoma tissues than in situ ductal carcinoma patients.

CONCLUSION: We think that astaxanthin is a promising therapeutic agent for invasive ductal carcinoma patients. The effects of astaxanthin on metastasis in breast cancer should be investigated further based on these results.

KEY WORDS: Breast, cancer, metastasis.}, } @article {pmid34094915, year = {2021}, author = {Wang, Y and Liang, F and Zhou, Y and Qiu, J and Lv, Q and Du, Z}, title = {Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {634569}, pmid = {34094915}, issn = {2234-943X}, abstract = {INTRODUCTION: Breast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.

METHODS: Laser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.

RESULTS: Two modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e-07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e-12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.

CONCLUSIONS: Five hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.}, } @article {pmid34093928, year = {2021}, author = {Thompson, HK and Spicer, PJ}, title = {Recurrent breast cancer diagnosis delayed by COVID-19 pandemic.}, journal = {Radiology case reports}, volume = {16}, number = {9}, pages = {2450-2453}, pmid = {34093928}, issn = {1930-0433}, abstract = {We describe the case of a 64-year-old female with a no relevant medical history. Screening mammography in March 2020 demonstrated calcifications in the right breast, and a diagnostic mammogram was recommended. In the months that followed, the patient experienced tissue changes in the right breast but avoided returning to the facility as the COVID-19 pandemic worsened. The patient returned for a diagnostic mammogram in September of 2020, which indicated suspicious lymph nodes and an increase in calcifications. Further analysis through ultrasound-guided core biopsy ultimately led to a right mastectomy and lymph node biopsy, which were performed in October 2020. Pathology results confirmed the diagnosis of invasive ductal carcinoma with lobular features.}, } @article {pmid34084681, year = {2021}, author = {Ahmed, M and Frederickson, J and Khan, K and Bashir, K}, title = {Rhabdomyolysis After Total Abdominal Hysterectomy Requiring Urgent Hemodialysis Due to Hyperkalemia.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14757}, pmid = {34084681}, issn = {2168-8184}, abstract = {A 63-year-old woman with a past medical history of invasive ductal carcinoma of the breast, status post lumpectomy and chemoradiation, 15 cm left inguinal-femoral enlarged lymph node consistent with high-grade serous carcinoma of the ovary and 4.7 cm right adnexal mass underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection with cystoscopy and bilateral ureteral catheter placement. There was no intraoperative complication. After surgery, patient's urine output decreased, and she developed acute kidney injury (AKI). Initially, it was thought that her reduced output might be due to surgery/anesthesia. She also developed arm and leg weakness raising suspicion for stroke. The neurological workup was unremarkable for any acute abnormality. Her creatinine kinase (CK) level was >20,000 u/l consistent with rhabdomyolysis. She was hydrated aggressively and required hemodialysis due to hyperkalemia. During the hospital course, her kidney function improved, and rhabdomyolysis resolved, and she did not require dialysis after discharge.}, } @article {pmid34083791, year = {2021}, author = {Zhao, E and Stone, MR and Ren, X and Guenthoer, J and Smythe, KS and Pulliam, T and Williams, SR and Uytingco, CR and Taylor, SEB and Nghiem, P and Bielas, JH and Gottardo, R}, title = {Spatial transcriptomics at subspot resolution with BayesSpace.}, journal = {Nature biotechnology}, volume = {39}, number = {11}, pages = {1375-1384}, pmid = {34083791}, issn = {1546-1696}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Cluster Analysis ; Gene Expression Profiling/methods ; Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; }, abstract = {Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.}, } @article {pmid34073849, year = {2021}, author = {Ali, R and Al Zahrani, H and Barhoumi, T and Alhallaj, A and Mashhour, A and Alshammari, MA and Alshawakir, YA and Baz, O and Alanazi, AH and Khan, AL and Al Nikhli, H and Al Balwi, MA and Al Riyees, L and Boudjelal, M}, title = {Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34073849}, issn = {2073-4409}, support = {RC18/173//KAIMRC/ ; }, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Cell Line, Tumor ; *Cell Proliferation ; Female ; Humans ; Neoplasm Proteins/*metabolism ; *Neoplastic Stem Cells/metabolism/pathology ; *Triple Negative Breast Neoplasms/metabolism/pathology ; }, abstract = {In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells' expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.}, } @article {pmid34071029, year = {2021}, author = {Roy, SD and Das, S and Kar, D and Schwenker, F and Sarkar, R}, title = {Computer Aided Breast Cancer Detection Using Ensembling of Texture and Statistical Image Features.}, journal = {Sensors (Basel, Switzerland)}, volume = {21}, number = {11}, pages = {}, pmid = {34071029}, issn = {1424-8220}, mesh = {*Breast Neoplasms/diagnosis ; *Carcinoma, Intraductal, Noninfiltrating ; Computers ; Humans ; Machine Learning ; Neural Networks, Computer ; }, abstract = {Breast cancer, like most forms of cancer, is a fatal disease that claims more than half a million lives every year. In 2020, breast cancer overtook lung cancer as the most commonly diagnosed form of cancer. Though extremely deadly, the survival rate and longevity increase substantially with early detection and diagnosis. The treatment protocol also varies with the stage of breast cancer. Diagnosis is typically done using histopathological slides from which it is possible to determine whether the tissue is in the Ductal Carcinoma In Situ (DCIS) stage, in which the cancerous cells have not spread into the encompassing breast tissue, or in the Invasive Ductal Carcinoma (IDC) stage, wherein the cells have penetrated into the neighboring tissues. IDC detection is extremely time-consuming and challenging for physicians. Hence, this can be modeled as an image classification task where pattern recognition and machine learning can be used to aid doctors and medical practitioners in making such crucial decisions. In the present paper, we use an IDC Breast Cancer dataset that contains 277,524 images (with 78,786 IDC positive images and 198,738 IDC negative images) to classify the images into IDC(+) and IDC(-). To that end, we use feature extractors, including textural features, such as SIFT, SURF and ORB, and statistical features, such as Haralick texture features. These features are then combined to yield a dataset of 782 features. These features are ensembled by stacking using various Machine Learning classifiers, such as Random Forest, Extra Trees, XGBoost, AdaBoost, CatBoost and Multi Layer Perceptron followed by feature selection using Pearson Correlation Coefficient to yield a dataset with four features that are then used for classification. From our experimental results, we found that CatBoost yielded the highest accuracy (92.55%), which is at par with other state-of-the-art results-most of which employ Deep Learning architectures. The source code is available in the GitHub repository.}, } @article {pmid34070538, year = {2021}, author = {Cheng, CW and Liao, WL and Chen, PM and Yu, JC and Shiau, HP and Hsieh, YH and Lee, HJ and Cheng, YC and Wu, PE and Shen, CY}, title = {MiR-139 Modulates Cancer Stem Cell Function of Human Breast Cancer through Targeting CXCR4.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34070538}, issn = {2072-6694}, support = {MOST 102-2628-B-040-002-MY3; MOST 103-2811-B-040-001//Ministry of Science and Technology, Taiwan/ ; }, abstract = {Elevated expression of C-X-C motif chemokine receptor 4 (CXCR4) correlates with chemotaxis, invasion, and cancer stem cell (CSC) properties within several solid-tumor malignancies. Recent studies reported that microRNA (miRNA) modulates the stemness of embryonic stem cells. We aimed to investigate the role of miRNA, via CXCR4-modulation, on CSC properties in breast cancer using cell lines and xenotransplantation mouse model and evaluated miR-193 levels in 191 patients with invasive ductal carcinoma. We validated miR-139 directly targets the 3'-untranslated region of CXCR4. Hoechst 33342 fluorescence-activated cell sorting (FACS) and sphere-forming assay were used to identify CSCs. MiR-139 suppressed breast CSCs with mesenchymal traits; led to decreased migration and invasion abilities through down-regulating CXCR4/p-Akt signaling. In lung cancer xenograft model of nude mice transplanted with human miR-139-carrying MDA-MB-231 cells, metastatic lung nodules were suppressed. Clinically, microdissected breast tumor tissues showed miR-139 reduction, compared to adjacent non-tumor tissues, that was significantly associated with worse clinicopathological features, including larger tumor size, advanced tumor stage and lymph node metastasis; moreover, reduced miR-139 level was predominately occurred in late-stage HER2-oreexpression tumors. Collectively, our findings highlight miR-139-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.}, } @article {pmid34062284, year = {2021}, author = {Salles, DC and Vidotto, T and Faisal, FA and Tosoian, JJ and Guedes, LB and Muranyi, A and Bai, I and Singh, S and Yan, D and Shanmugam, K and Lotan, TL}, title = {Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {23}, number = {8}, pages = {1030-1041}, pmid = {34062284}, issn = {1943-7811}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Molecular Diagnostic Techniques/methods/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics/*metabolism ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/genetics/*metabolism/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Reproducibility of Results ; }, abstract = {This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.}, } @article {pmid34058243, year = {2021}, author = {Hesterberg, AB and Gordetsky, JB and Hurley, PJ}, title = {Cribriform Prostate Cancer: Clinical Pathologic and Molecular Considerations.}, journal = {Urology}, volume = {155}, number = {}, pages = {47-54}, pmid = {34058243}, issn = {1527-9995}, support = {R01 CA211695/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*genetics/pathology ; }, abstract = {Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations.}, } @article {pmid34056582, year = {2021}, author = {Tran, V and Kim, R and Maertens, M and Hartung, T and Maertens, A}, title = {Similarities and Differences in Gene Expression Networks Between the Breast Cancer Cell Line Michigan Cancer Foundation-7 and Invasive Human Breast Cancer Tissues.}, journal = {Frontiers in artificial intelligence}, volume = {4}, number = {}, pages = {674370}, pmid = {34056582}, issn = {2624-8212}, abstract = {Failure to adequately characterize cell lines, and understand the differences between in vitro and in vivo biology, can have serious consequences on the translatability of in vitro scientific studies to human clinical trials. This project focuses on the Michigan Cancer Foundation-7 (MCF-7) cells, a human breast adenocarcinoma cell line that is commonly used for in vitro cancer research, with over 42,000 publications in PubMed. In this study, we explore the key similarities and differences in gene expression networks of MCF-7 cell lines compared to human breast cancer tissues. We used two MCF-7 data sets, one data set collected by ARCHS4 including 1032 samples and one data set from Gene Expression Omnibus GSE50705 with 88 estradiol-treated MCF-7 samples. The human breast invasive ductal carcinoma (BRCA) data set came from The Cancer Genome Atlas, including 1212 breast tissue samples. Weighted Gene Correlation Network Analysis (WGCNA) and functional annotations of the data showed that MCF-7 cells and human breast tissues have only minimal similarity in biological processes, although some fundamental functions, such as cell cycle, are conserved. Scaled connectivity-a network topology metric-also showed drastic differences in the behavior of genes between MCF-7 and BRCA data sets. Finally, we used canSAR to compute ligand-based druggability scores of genes in the data sets, and our results suggested that using MCF-7 to study breast cancer may lead to missing important gene targets. Our comparison of the networks of MCF-7 and human breast cancer highlights the nuances of using MCF-7 to study human breast cancer and can contribute to better experimental design and result interpretation of study involving this cell line.}, } @article {pmid34055313, year = {2021}, author = {Jayawardane, M and Gankanda, W and Gunathilake, M}, title = {Prevalence of pre-operative anxiety and associated factors among a group of women undergoing gynaecological surgeries at a single unit in a tertiary care hospital in Sri Lanka.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {74}, pmid = {34055313}, issn = {2046-1402}, mesh = {Adult ; *Anxiety/epidemiology ; Cross-Sectional Studies ; Female ; *Gynecologic Surgical Procedures/adverse effects ; Humans ; Middle Aged ; Prevalence ; Sri Lanka/epidemiology ; Tertiary Care Centers ; }, abstract = {Background: Surgery-related anxiety is universal, leading to complications. The objective of this study was to assess the prevalence of pre-operative anxiety levels among a group of patients. Methods: A descriptive cross-sectional study of 64 women was conducted in a tertiary care hospital, Sri Lanka. Patients who underwent emergency surgeries, those with mental illnesses or those aged <18 years were excluded. Pre-operative assessment was done one day prior to the surgery using a self-administered Sinhala validated Amsterdam-Preoperative-Anxiety-and-Information-Scale (APAIS), Hospital Anxiety and Depression Scale (HADS) and Visual-Analogue-Scale (VAS). The APAIS consists of six questions which assess three anxiety components: anesthesia-related-anxiety (Sum A), surgery-related-anxiety (Sum S) and information-desire-component (Sum IDC). The combined score (Sum C) is given by the total of Sum A and Sum S. A Sum C of ≥11 indicates significant anxiety. Results: The mean age of participants was 38.03 years (SD=13.53 years). The mean total score of APAIS was 10.36 (4.06), of HADS was 5.734 (4.487) and of VAS was 3.156 (2.773). All scores were higher in participants <50 years. There were negative correlations between age and anxiety levels in VAS and APAIS scales; the Sum IDC in APAIS (r=-0.416, p=0.001) and VAS scores (r=-246, p=0.050) showed significant negative correlations. Excepting Sum IDC all APAIS, HADS and VAS scores were higher among the group without insurance; despite free healthcare. However only Sum S (t=-3.716, p=0.000) and Sum C (t=-2.281, p=0.026) in APAIS, HADS (t=-3.412, p=0.001) and VAS (t=-2.135, p=0.037) had statistically higher values. Anxiety scores were higher in the group that underwent minor surgeries but where not significantly related to education level, marital status, income, employment or living status. Conclusions: Pre-operative anxiety is common. Age <50 years, lacking insurance cover and undergoing minor surgeries are associated with increased pre-operative anxiety levels. Screening and appropriate interventions would be beneficial.}, } @article {pmid34054577, year = {2021}, author = {Gerasimova-Chechkina, E and Toner, BC and Batchelder, KA and White, B and Freynd, G and Antipev, I and Arneodo, A and Khalil, A}, title = {Loss of Mammographic Tissue Homeostasis in Invasive Lobular and Ductal Breast Carcinomas vs. Benign Lesions.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {660883}, pmid = {34054577}, issn = {1664-042X}, support = {R15 CA246335/CA/NCI NIH HHS/United States ; }, abstract = {The 2D wavelet transform modulus maxima (WTMM) method is used to perform a comparison of the spatial fluctuations of mammographic breast tissue from patients with invasive lobular carcinoma, those with invasive ductal carcinoma, and those with benign lesions. We follow a procedure developed and validated in a previous study, in which a sliding window protocol is used to analyze thousands of small subregions in a given mammogram. These subregions are categorized according to their Hurst exponent values (H): fatty tissue (H ≤ 0.45), dense tissue (H ≥ 0.55), and disrupted tissue potentially linked with tumor-associated loss of homeostasis (0.45 < H < 0.55). Following this categorization scheme, we compare the mammographic tissue composition of the breasts. First, we show that cancerous breasts are significantly different than breasts with a benign lesion (p-value ∼ 0.002). Second, the asymmetry between a patient's cancerous breast and its contralateral counterpart, when compared to the asymmetry from patients with benign lesions, is also statistically significant (p-value ∼ 0.006). And finally, we show that lobular and ductal cancerous breasts show similar levels of disruption and similar levels of asymmetry. This study demonstrates reproducibility of the WTMM sliding-window approach to help detect and characterize tumor-associated breast tissue disruption from standard mammography. It also shows promise to help with the detection lobular lesions that typically go undetected via standard screening mammography at a much higher rate than ductal lesions. Here both types are assessed similarly.}, } @article {pmid34050841, year = {2023}, author = {Ferencz-Kaddari, M and Reizer, A and Koslowsky, M and Nakash, O and Konas, S}, title = {Psychiatric Hospital Ethics Committee Discussions Over a Span of Nearly Three Decades.}, journal = {HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues}, volume = {35}, number = {1}, pages = {55-71}, pmid = {34050841}, issn = {1572-8498}, mesh = {Humans ; *Ethics Committees, Clinical ; *Confidentiality ; Health Personnel ; }, abstract = {Various types of health settings use clinical ethics committees (CEC) to deal with the ethical issues that confront both healthcare providers and their patients. Although these committees are now more common than ever, changes in the content of ethical dilemmas through the years is still a relatively unexplored area of research. The current study examines the major topics brought to the CEC of a psychiatric hospital in Israel and explores whether there were changes in their frequency across nearly three decades. The present paper reports on a thematic analysis of the written verbatim transcripts from 466 ethical topics brought to the CEC between the years 1991 and 2016. The following major topics related to ethical dilemmas were identified: confidentiality (30%), patient autonomy (23%), health records (14%), dual relationship (12%), allocation of resources (11%), inappropriate professional and personal conduct (9%), and multicultural sensitivity (1%). Topics related to confidentiality increased significantly over the years, as did inappropriate professional and personal conduct. In addition, the analysis showed that the content of the ethical cases and the resolutions suggested by the CEC also varied over the years. In conclusion, although most ethical topics have remained relatively stable over time, the discourse around them has evolved, requiring a dynamic assessment and reflection by the mental health practitioners serving as members of a CEC.}, } @article {pmid34048471, year = {2021}, author = {Brock, EJ and Jackson, RM and Boerner, JL and Li, Q and Tennis, MA and Sloane, BF and Mattingly, RR}, title = {Sprouty4 negatively regulates ERK/MAPK signaling and the transition from in situ to invasive breast ductal carcinoma.}, journal = {PloS one}, volume = {16}, number = {5}, pages = {e0252314}, pmid = {34048471}, issn = {1932-6203}, support = {F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; }, abstract = {Breast ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC). It is still unclear which DCIS will become invasive and which will remain indolent. Patients often receive surgery and radiotherapy, but this early intervention has not produced substantial decreases in late-stage disease. Sprouty proteins are important regulators of ERK/MAPK signaling and have been studied in various cancers. We hypothesized that Sprouty4 is an endogenous inhibitor of ERK/MAPK signaling and that its loss/reduced expression is a mechanism by which DCIS lesions progress toward IDC, including triple-negative disease. Using immunohistochemistry, we found reduced Sprouty4 expression in IDC patient samples compared to DCIS, and that ERK/MAPK phosphorylation had an inverse relationship to Sprouty4 expression. These observations were reproduced using a 3D culture model of disease progression. Knockdown of Sprouty4 in MCF10.DCIS cells increased ERK/MAPK phosphorylation as well as their invasive capability, while overexpression of Sprouty4 in MCF10.CA1d IDC cells reduced ERK/MAPK phosphorylation, invasion, and the aggressive phenotype exhibited by these cells. Immunofluorescence experiments revealed reorganization of the actin cytoskeleton and relocation of E-cadherin back to the cell surface, consistent with the restoration of adherens junctions. To determine whether these effects were due to changes in ERK/MAPK signaling, MEK1/2 was pharmacologically inhibited in IDC cells. Nanomolar concentrations of MEK162/binimetinib restored an epithelial-like phenotype and reduced pericellular proteolysis, similar to Sprouty4 overexpression. From these data we conclude that Sprouty4 acts to control ERK/MAPK signaling in DCIS, thus limiting the progression of these premalignant breast lesions.}, } @article {pmid34044957, year = {2021}, author = {Yang, L and Kaziem, AE and Lin, Y and Li, C and Tan, Y and Huang, S and Cheng, D and Xu, H and Zhang, Z}, title = {Carboxylated β-cyclodextrin anchored hollow mesoporous silica enhances insecticidal activity and reduces the toxicity of indoxacarb.}, journal = {Carbohydrate polymers}, volume = {266}, number = {}, pages = {118150}, doi = {10.1016/j.carbpol.2021.118150}, pmid = {34044957}, issn = {1879-1344}, mesh = {Animals ; Drug Carriers/*chemistry/toxicity ; Insecticides/*pharmacology ; Nanoparticles/*chemistry/toxicity ; Oxazines/*pharmacology ; Porosity ; Silicon Dioxide/*chemistry/toxicity ; Spodoptera/drug effects ; Zebrafish ; beta-Cyclodextrins/*chemistry/toxicity ; }, abstract = {In this study, a pesticide controlled release system with dual response characteristics of pH and enzyme triggering was developed. Indoxacarb (IDC) was loaded into hollow mesoporous silica (HMS) nanoparticles, carboxylated β-cyclodextrin (β-CD) acted as a capping molecule to couple with the amino-functionalized HMS, and their well-defined morphological structures were confirmed by scanning electron microscopy and transmission electron microscopy. The results showed that the prepared IDC loaded HMS-CD had high loading efficiency (26.42%, w/w) and showed excellent dual response properties to pH and the α-amylase enzyme. IDC loaded HMS-CD nanoparticles showed better insecticidal activity against Spodoptera frugiperda than applying the same dose of IDC emulsifiable concentrate, and the toxicity of IDC loaded HMS-CD to zebrafish was reduced by more than 5-fold, indicating that insecticide delivery systems based on β-CD-anchored HMS nanoparticles could potentially be applied for sustainable control of pests and reduce harm to non-target organisms and the environment.}, } @article {pmid34044580, year = {2021}, author = {Markus, HS and Egle, M and Croall, ID and Sari, H and Khan, U and Hassan, A and Harkness, K and MacKinnon, A and O'Brien, JT and Morris, RG and Barrick, TR and Blamire, AM and Tozer, DJ and Ford, GA and , }, title = {PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.}, journal = {Stroke}, volume = {52}, number = {8}, pages = {2484-2493}, doi = {10.1161/STROKEAHA.120.032054}, pmid = {34044580}, issn = {1524-4628}, mesh = {Aged ; Antihypertensive Agents/*therapeutic use ; Blood Pressure ; Cerebral Small Vessel Diseases/complications/*diagnostic imaging/physiopathology ; *Cognition ; Diffusion Tensor Imaging ; Disease Progression ; Female ; Humans ; Hypertension/complications/*drug therapy/physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; *Patient Care Planning ; Stroke, Lacunar/complications/*diagnostic imaging/physiopathology ; White Matter/*diagnostic imaging ; }, abstract = {[Figure: see text].}, } @article {pmid34044549, year = {2021}, author = {Zhang, W and Qu, X and Fang, Y}, title = {Recurrent radiation-associated leiomyosarcoma after postoperative radiotherapy for breast invasive ductal carcinoma: a case report and literature review.}, journal = {Annals of palliative medicine}, volume = {10}, number = {7}, pages = {8467-8473}, doi = {10.21037/apm-20-2561}, pmid = {34044549}, issn = {2224-5839}, mesh = {*Breast Neoplasms/radiotherapy ; *Carcinoma, Ductal ; Female ; Humans ; *Leiomyosarcoma ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; }, abstract = {Radiation-associated leiomyosarcoma has a poor prognosis. Fewer than 20 cases of radiation-associated leiomyosarcoma of the breast have been reported in the literature to date. We report the first case of recurrent radiation-associated leiomyosarcoma after invasive ductal carcinoma postoperative radiotherapy. A 45-year-old female patient with no familial history of cancer underwent breast-conserving surgery (BCS) and dissection of axillary lymph nodes for invasive ductal carcinoma in the right upper outer region in 2014. After the operation, she received adjuvant chemotherapy followed by radiotherapy and endocrine therapy. She came to our institution for a lump in the right breast radiation region in 2019. Ultrasonography revealed an oval mass, with ill-defined borders, irregular margins, and speculation at 6 o'clock direction of the right breast, approximately 2.5 cm from the nipple. Ultimately, excisional biopsy established the pathological diagnosis of leiomyosarcoma. The female then underwent simple mastectomy of the right breast. The patient received no radiation or chemotherapy after the simple mastectomy. After 13 months of follow-up, a lump was found in the right chest wall and axillary levels of the radiation region. Excisional biopsy confirmed the pathological diagnosis of leiomyosarcoma. This rare case indicated that simple mastectomy seemed to be inadequate treatment for radiation-associated leiomyosarcoma.}, } @article {pmid34035906, year = {2020}, author = {Maaravi, Y and Heller, B}, title = {Studying the prominence effect amid the COVID-19 crisis: implications for public health policy decision-making.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {1356}, pmid = {34035906}, issn = {2046-1402}, mesh = {Bias ; *COVID-19 ; Health Policy ; Humans ; SARS-CoV-2 ; }, abstract = {The novel coronavirus disease 2019 (COVID-19) has brought with it crucial policy- and decision-making situations, especially when making judgments between financial and health concerns. One particularly relevant decision-making phenomenon is the prominence effect, where decision-makers base their decisions on the most prominent attribute of the object at hand (e.g., health concerns) rather than weigh all the attributes together. This bias diminishes when the decision-making mode inhibits heuristic processes. In this study, we tested the prominence of health vs. financial concerns across two decision-making modes - choice (prone to heuristics) and matching (mitigates heuristics) - during the peak of the COVID-19 in the UK using Tversky et al.'s classic experimental paradigm. We added to the classic experimental design a priming condition. Participants were presented with two casualty-minimization programs, differing in lives saved and costs: program X would save 100 lives at the cost of 55-million-pound sterling, whereas program Y would save 30 lives at the cost of 12-million-pound sterling. Half of the participants were required to choose between the programs (choice condition). The other half were not given the cost of program X and were asked to determine what the cost should be to make it as equally attractive as the program Y. Participants in both groups were primed for either: a) financial concerns; b) health concerns; or c) control (no priming). Results showed that in the choice condition, unless primed for financial concerns, health concerns are more prominent. In the matching condition, on the other hand, the prominence of health concerns did not affect decision-makers, as they all "preferred" the cheaper option. These results add further support to the practical relevance of using the proper decision-making modes in times of consequential crises where multiple concerns, interests, and parties are involved.}, } @article {pmid34042093, year = {2021}, author = {Guerrieri, C and Sesti, J and Gupta, S and Hudacko, R}, title = {Pagetoid involvement of bronchioles by metastatic breast carcinoma.}, journal = {Pathologica}, volume = {113}, number = {2}, pages = {121-125}, pmid = {34042093}, issn = {1591-951X}, mesh = {Adult ; *Breast Neoplasms/diagnostic imaging/surgery ; *Bronchioles ; Female ; Humans ; }, abstract = {We report a case of a 36-year-old female with endobronchiolar spread of breast carcinoma in the lung. The patient had recently been diagnosed with invasive ductal breast carcinoma and imaging of the lungs revealed bilateral lung nodules. She then underwent a wedge resection of a lung nodule. The biopsy revealed a subpleural metastatic nodule of invasive ductal carcinoma with an intra-alveolar pattern of spread at its advancing edge. Several smaller foci of intra-alveolar tumor were noted as well as pagetoid spread of tumor cells along a 0.9 mm wide bronchiole. The neoplastic cells were TTF-1 negative, GATA3 positive and ER positive. This is the third reported case of pagetoid spread of metastatic breast carcinoma along the bronchial tree. This case emphasizes the importance of examining not only bronchi but also bronchioles to detect this unusual pattern of spread of metastatic breast carcinoma in lung resection specimens.}, } @article {pmid34038841, year = {2021}, author = {Icht, M and Ben-David, BM}, title = {Evaluating rate and accuracy of real word vs. non-word diadochokinetic productions from childhood to early adulthood in Hebrew speakers.}, journal = {Journal of communication disorders}, volume = {92}, number = {}, pages = {106112}, doi = {10.1016/j.jcomdis.2021.106112}, pmid = {34038841}, issn = {1873-7994}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Humans ; *Language ; Linguistics ; *Speech ; Speech Articulation Tests ; Speech Disorders ; Young Adult ; }, abstract = {BACKGROUND: Oral-Diadochokinesis (oral-DDK) tasks measure how quickly and accurately one can repeat a series of target sounds. Thus, they are a popular tool for evaluating oral-motor skills for individuals with various speech disorders. Typically, oral-DDK tasks involve rapid repetition of non-words. For several populations (e.g., young children, older adults), it has been suggested that repetitions of real words may be more suitable, commonly resulting in faster rates. Yet, the literature is either silent or inconsistent regarding this real-word repetition advantage for other age groups, from preschoolers to young adults. It is not clear whether performance accuracy is affected as well. Specifically, for Hebrew speakers, this data is missing.

AIMS: The goal of this study was to compare rate and accuracy for non-word and real-word repetition, in four groups of Hebrew-speaking individuals; preschoolers (5 years old), younger elementary school children (7 years old), adolescents (15 years old) and young adults (25 years old). Secondary goals were to provide a developmental pattern for oral-DDK rates for Hebrew speakers, and to compare it to the English norms.

METHODS & PROCEDURES: All participants (n=150) had typical speech and language development. They were asked to repeat "pataka" (non-word) and "bodeket" (Hebrew real word) as quickly and accurately as possible for 10 sec. Production rates (syllables per second) and accuracy (on a 5-point scale) were measured.

OUTCOMES & RESULTS: As expected, oral-DDK rates gradually increased with age, with similar rates for both real- and non-words. Accuracy scores were higher for real- than non-word repetition, across all age groups. For the group of school-age children, the Hebrew rates differed from the English ones.

A real-word repetition advantage was documented only for repetition accuracy, but not for rate. These findings can be explained as each stimulus involves different demands on an individual's neuro-motor and linguistic processing abilities. Further research using real- and non-word tasks should be conducted with clinical populations to assess whether both procedures could assist in differential diagnosis between various speech disorders. Finally, the large differences between children of different ages, as well as the apparent rate differences between Hebrew and English, highlight the need to create age- and language-sensitive norms.}, } @article {pmid34036425, year = {2021}, author = {Mourad, S and Ayoub, GM and Al Hindi, M and Zayyat, RM}, title = {Occurrence and hazard assessment of natural radioactivity in drinking water in South Lebanon.}, journal = {Environmental monitoring and assessment}, volume = {193}, number = {6}, pages = {358}, pmid = {34036425}, issn = {1573-2959}, mesh = {Adult ; Child ; *Drinking Water/analysis ; Humans ; Infant ; Lebanon ; Radiation Dosage ; *Radiation Monitoring ; *Radioactivity ; *Radon/analysis ; *Water Pollutants, Radioactive/analysis ; Water Supply ; }, abstract = {This study is intended to assess the natural radioactivity in the drinking water in the southern region of Lebanon and to determine its suitability for human consumption. In this context, activity concentrations for gross alpha, gross beta, [238]U, [234]U, and radon from selected drinking water sources, wells, and springs and the corresponding tap water, in the area under investigation, were determined during both the wet and the dry seasons. The maximum recorded activities of gross alpha, gross beta, and radon measured using liquid scintillation counter were found to be 374.6 ± 11.5 mBq L[-1] for gross alpha, 418 ± 12 mBq L[-1] for gross beta, and 42,900 ± 370 mBq L[-1] for radon. Whereas, alpha spectroscopy analysis for uranium content showed maximum activities of 53.7 ± 2.1 mBq L[-1] for [238]U and 55.9 ± 2.3 mBq L[-1] for [234]U. Significant seasonal activity variation between wet and dry season was noticed only in gross alpha concentrations. In addition, significant variation between sources and tap water was recorded only in radon concentrations. Whereas, no significant variation was noted in radioactivity concentrations in waters from springs and those from wells. In contrast to all sampled locations, the annual effective dose of only one sampled well (Aitaroun) exceeded the WHO individual dose criterion (IDC) level of 100 µSv year[-1] and recorded an annual effective dose of 170 µSv year[-1], 103 µSv year[-1], and 127 µSv year[-1] for infants, children, and adults, respectively.}, } @article {pmid34035435, year = {2021}, author = {Vaidya, JS and Bulsara, M and Baum, M and Wenz, F and Massarut, S and Pigorsch, S and Alvarado, M and Douek, M and Saunders, C and Flyger, H and Eiermann, W and Brew-Graves, C and Williams, NR and Potyka, I and Roberts, N and Bernstein, M and Brown, D and Sperk, E and Laws, S and Sütterlin, M and Corica, T and Lundgren, S and Holmes, D and Vinante, L and Bozza, F and Pazos, M and Blanc-Onfroy, ML and Gruber, G and Polkowski, W and Dedes, KJ and Niewald, M and Blohmer, J and McReady, D and Hoefer, R and Kelemen, P and Petralia, G and Falzon, M and Joseph, D and Tobias, JS}, title = {New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.}, journal = {British journal of cancer}, volume = {125}, number = {3}, pages = {380-389}, pmid = {34035435}, issn = {1532-1827}, support = {14/49/13/DH_/Department of Health/United Kingdom ; 07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental/*methods ; Middle Aged ; Prognosis ; Survival Analysis ; Treatment Outcome ; Tumor Burden ; Whole-Body Irradiation ; }, abstract = {BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses.

METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT.

RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091.

CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect.

TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).}, } @article {pmid34034113, year = {2021}, author = {Weinstein, G}, title = {Is the EHT black hole experiment a new experiment in the guise of an old experiment?.}, journal = {Studies in history and philosophy of science}, volume = {88}, number = {}, pages = {41-49}, doi = {10.1016/j.shpsa.2021.05.002}, pmid = {34034113}, issn = {0039-3681}, mesh = {*Telescopes ; }, abstract = {This paper analyzes the experiment presented in 2019 by the Event Horizon Telescope (EHT) Collaboration that unveiled the first image of the supermassive black hole at the center of galaxy M87. The intended aim of the paper is to assess whether the EHT Collaboration has made an "inference to the best explanation" (IBE) to conclude that the data effectively confirm the hypothesis that the object at the center of M87 is in fact a supermassive Kerr rotating black hole. I demonstrate that the EHT Collaboration has applied an IBE. It is shown that the hypothesis that at the center of M87 there is a supermassive Kerr rotating black hole was already the best explanation at the time in which the 2017 EHT experiment was conducted. My analysis is intertwined with considerations on realist and empiricist interpretations of IBE, which are used to assess whether the conclusion that the object at the center of M87 is a Kerr rotating black hole implies holding a realist commitment with respect to such object.}, } @article {pmid34031394, year = {2021}, author = {Amit, I and Iancu, O and Levy-Jurgenson, A and Kurgan, G and McNeill, MS and Rettig, GR and Allen, D and Breier, D and Ben Haim, N and Wang, Y and Anavy, L and Hendel, A and Yakhini, Z}, title = {CRISPECTOR provides accurate estimation of genome editing translocation and off-target activity from comparative NGS data.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3042}, pmid = {34031394}, issn = {2041-1723}, mesh = {Algorithms ; *CRISPR-Cas Systems ; Computational Biology/*methods ; DNA-Binding Proteins/genetics ; Gene Editing/*methods ; HEK293 Cells ; Homeodomain Proteins/genetics ; Humans ; Nuclear Proteins/genetics ; Software ; Transcription Factors/genetics ; }, abstract = {Controlling off-target editing activity is one of the central challenges in making CRISPR technology accurate and applicable in medical practice. Current algorithms for analyzing off-target activity do not provide statistical quantification, are not sufficiently sensitive in separating signal from noise in experiments with low editing rates, and do not address the detection of translocations. Here we present CRISPECTOR, a software tool that supports the detection and quantification of on- and off-target genome-editing activity from NGS data using paired treatment/control CRISPR experiments. In particular, CRISPECTOR facilitates the statistical analysis of NGS data from multiplex-PCR comparative experiments to detect and quantify adverse translocation events. We validate the observed results and show independent evidence of the occurrence of translocations in human cell lines, after genome editing. Our methodology is based on a statistical model comparison approach leading to better false-negative rates in sites with weak yet significant off-target activity.}, } @article {pmid34031061, year = {2021}, author = {Connolly, C and Cobain, E and Hughes, T}, title = {Anti-amphiphysin positive stiff-person syndrome due to invasive ductal carcinoma in a male patient.}, journal = {BMJ case reports}, volume = {14}, number = {5}, pages = {}, pmid = {34031061}, issn = {1757-790X}, mesh = {Autoantibodies ; *Breast Neoplasms ; *Carcinoma, Ductal ; Humans ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; *Stiff-Person Syndrome/diagnosis/drug therapy ; }, abstract = {Stiff-person syndrome (SPS) is a rare progressive neurological disorder characterised by painful muscle spasms and progressive muscle rigidity, leading in some cases to impaired ambulation. Anti-amphiphysin positive SPS is a paraneoplastic variant, frequently associated with breast carcinomas and small cell lung cancers. We report the case of a 53-year-old patient who developed symptoms of anti-amphiphysin positive SPS 3 years before being diagnosed with invasive ductal carcinoma. Specifically, computed tomography (CT) of the chest, abdomen and pelvis, positron emission tomography-CT (PET-CT), mammogram, colonoscopy and magnetic resonance imaging (MRI) did not identify malignancy during the 3 years following the onset of symptoms. Following diagnosis of invasive ductal carcinoma and completion of curative-intent oncological treatment, the patient experienced improvement, though not complete resolution, in his SPS symptoms. This case highlights the importance of thorough oncological workup when clinical presentation and diagnostic testing are suggestive of anti-amphiphysin positive SPS.}, } @article {pmid34022480, year = {2021}, author = {Hoshina, H and Takei, H and Nakamura, M and Nishimoto, F and Hanamura, S}, title = {Carcinomatous cirrhosis as radiographically occult liver metastases of breast cancer: A systematic literature review.}, journal = {Cancer treatment and research communications}, volume = {28}, number = {}, pages = {100388}, doi = {10.1016/j.ctarc.2021.100388}, pmid = {34022480}, issn = {2468-2942}, mesh = {Ascites/*diagnosis/etiology ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Liver Neoplasms/complications/*diagnosis/secondary ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; }, abstract = {In the present study, we aimed to clarify features of carcinomatous cirrhosis from breast cancer presenting as refractory transudate ascites and acute liver failure. In our systematic literature review, we identified 26 studies and 31 cases including our case of this rare condition. Our patient was a 49-year-old woman with a history of ascites and liver failure for the past 4 years and currently being treated for invasive ductal breast cancer. On radiography, she had occult liver metastases that were confirmed using laparoscopic liver biopsy. In the 31 cases, data on the reported year, age, type of primary breast cancer, time from breast cancer diagnosis, presence of ascites and/or varices, liver biopsy, diagnostic modalities, outcomes, and survival were documented and analyzed. All cases were reported during 1984-2020, with a mean patient age of 52.9 years. Eighteen patients (58.1%) were diagnosed with ductal breast cancer. Twenty-two patients (70.9%) had ascites. All patients had gradual progression to liver dysfunction. The following tests were performed: computed tomography (77.4%); ultrasound (58.0%); liver biopsy (100%); postmortem biopsy (35.5%), transjugular liver biopsy (32.3%), and laparoscopic liver biopsy (3.2%). Outcomes were reported for 29 patients, of whom 24 (82.3%) died after 1 day to 16 months. Invasive ductal carcinoma was the most common histological type; however, invasive lobular carcinoma was more frequent (32.3%) than its reported incidence in the breast. Carcinomatous cirrhosis has poor prognosis at relatively rash and is difficult to diagnose with usual modalities. It may be associated with E-cadherin loss or CD44 pronouncement.}, } @article {pmid34017184, year = {2021}, author = {Li, C and Fang, H and Lu, H}, title = {Case Report of a Breast Mass with Three Types of Malignant Tumors-Squamous Cell Carcinoma, Invasive Ductal Carcinoma, and Breast Sarcoma.}, journal = {OncoTargets and therapy}, volume = {14}, number = {}, pages = {3193-3197}, pmid = {34017184}, issn = {1178-6930}, abstract = {Breast malignancy comprises malignant tumors originating from epithelial tissue and breast sarcoma arising from mesodermal tissues. Despite heterogeneity in tumors, most malignant tumors of the breast are composed of a single type of tumor. Here, we report a patient with breast tumor consisting of three different types of malignancies-squamous cell carcinoma, invasive ductal carcinoma, and high-grade breast sarcoma.}, } @article {pmid34016966, year = {2021}, author = {Georgiadi, A and Lopez-Salazar, V and Merahbi, RE and Karikari, RA and Ma, X and Mourão, A and Klepac, K and Bühler, L and Alfaro, AJ and Kaczmarek, I and Linford, A and Bosma, M and Shilkova, O and Ritvos, O and Nakamura, N and Hirose, S and Lassi, M and Teperino, R and Machado, J and Scheideler, M and Dietrich, A and Geerlof, A and Feuchtinger, A and Blutke, A and Fischer, K and Müller, TD and Kessler, K and Schöneberg, T and Thor, D and Hornemann, S and Kruse, M and Nawroth, P and Pivovarova-Ramich, O and Pfeiffer, AFH and Sattler, M and Blüher, M and Herzig, S}, title = {Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2999}, pmid = {34016966}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Adipocytes/metabolism ; Adipose Tissue, White/cytology/*metabolism ; Adolescent ; Adult ; Aged ; Animals ; CHO Cells ; Cohort Studies ; Cricetulus ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood/metabolism/prevention & control ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Female ; Gene Knockdown Techniques ; Glucose/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; Insulin/metabolism ; Insulin Resistance ; Islets of Langerhans/metabolism ; Liver/metabolism ; Male ; Membrane Proteins/administration & dosage/blood/genetics/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; NIH 3T3 Cells ; Prediabetic State/blood/drug therapy/etiology/*metabolism ; Primary Cell Culture ; Proteins/analysis/*metabolism ; Receptors, G-Protein-Coupled/blood/genetics/*metabolism ; Recombinant Fusion Proteins/administration & dosage/genetics/isolation & purification ; Young Adult ; }, abstract = {The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.}, } @article {pmid34016957, year = {2021}, author = {Egea, V and Kessenbrock, K and Lawson, D and Bartelt, A and Weber, C and Ries, C}, title = {Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.}, journal = {Cell death & disease}, volume = {12}, number = {6}, pages = {516}, pmid = {34016957}, issn = {2041-4889}, mesh = {Animals ; Cell Communication/physiology ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Chemokine CXCL12/*metabolism ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics/*metabolism/pathology ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; MicroRNAs/biosynthesis/*genetics ; Transfection ; Tumor Hypoxia/*physiology ; }, abstract = {Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.}, } @article {pmid34015750, year = {2021}, author = {de Araújo, RA and Cordero da Luz, FA and da Costa Marinho, E and Mendes, TR and Nascimento, CP and Ribeiro Delfino, PF and Antonioli, RM and Ruas, AC and Alves, AR and Araújo, BJ and de Paula Machado, JP and Guedes Pereira, TO and França do Espírito Santo, M and Barbosa Silva, MJ}, title = {Operable breast cancer: How not to worsen the prognosis, especially in triple negative and stage II tumors.}, journal = {Surgical oncology}, volume = {38}, number = {}, pages = {101596}, doi = {10.1016/j.suronc.2021.101596}, pmid = {34015750}, issn = {1879-3320}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology/*surgery ; }, abstract = {INTRODUCTION: Oncological surgery must follow some fundamental principles to be truly curative, one of which is the resection of the tumor with surgical margins free of neoplasia. In breast cancer, surgery with positive margins should be expanded immediately. There are probably different intensities, between the stages and molecular subtypes of operable breast cancer, of worsening prognosis due to the surgical margin compromised by the neoplasia in women not submitted to the necessary enlargement of the positive surgical margin. MATERIALS AND.

METHODS: Seven hundred and forty-seven women with invasive ductal carcinoma of the breast, analyzing anatomical-pathological information, types of surgery, molecular subtypes, and the presence or absence of the surgical margin compromised by neoplasia.

RESULTS: Sixty-one (8.2%) patients had positive surgical margin, causing 2.85 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis. In subgroup analysis, among stages I, II and III, stage II was the most negatively impacted, with those patients presenting 2.42 times more risk of distant metastasis and 4.94 times more risk of locoregional relapses compared to negative surgical margin by multivariate analysis. Among the molecular subtypes, Triple Negative tumors with a positive surgical margin had 3.56 times more risk of death, 4.98 times more risk of distant metastasis and 5.55 times more risk of locoregional relapse compared to negative surgical margin by multivariate analysis.

CONCLUSIONS: The positive surgical margin, especially in Stage II and Triple-Negative breast cancer patients negatively impact the patient's evolution, increasing risk of distant metastasis and death.}, } @article {pmid34014371, year = {2021}, author = {Giroud, M and Tsokanos, FF and Caratti, G and Kotschi, S and Khani, S and Jouffe, C and Vogl, ES and Irmler, M and Glantschnig, C and Gil-Lozano, M and Hass, D and Khan, AA and Garcia, MR and Mattijssen, F and Maida, A and Tews, D and Fischer-Posovszky, P and Feuchtinger, A and Virtanen, KA and Beckers, J and Wabitsch, M and Uhlenhaut, H and Blüher, M and Tuckermann, J and Scheideler, M and Bartelt, A and Herzig, S}, title = {HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.}, journal = {Diabetologia}, volume = {64}, number = {8}, pages = {1850-1865}, pmid = {34014371}, issn = {1432-0428}, mesh = {Adipocytes/*metabolism ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism ; Adult ; Aged ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cross-Sectional Studies ; Female ; Gene Expression Regulation/*physiology ; Gene Silencing ; Glucocorticoids/*pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity/*genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIMS/HYPOTHESIS: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.

METHODS: Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2[AdipoqCre]) and performed a large panel of metabolic tests.

RESULTS: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.

CONCLUSIONS/INTERPRETATION: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.

DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).}, } @article {pmid34011405, year = {2021}, author = {Dinca, SC and Greiner, D and Weidenfeld, K and Bond, L and Barkan, D and Jorcyk, CL}, title = {Novel mechanism for OSM-promoted extracellular matrix remodeling in breast cancer: LOXL2 upregulation and subsequent ECM alignment.}, journal = {Breast cancer research : BCR}, volume = {23}, number = {1}, pages = {56}, pmid = {34011405}, issn = {1465-542X}, support = {R25 GM123927/GM/NIGMS NIH HHS/United States ; 1C06RR020533/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; 0619737//National Science Foundation/ ; 0923535//National Science Foundation/ ; AR298//Smylie Family Cancer Fund (US)/ ; 2017237//United States - Israel Binational Science Foundation/ ; }, mesh = {Amino Acid Oxidoreductases/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Matrix/*metabolism ; Female ; Glycosylation ; Humans ; Inflammation ; Neoplasm Metastasis ; Oncostatin M/genetics/*metabolism/pharmacology ; Oncostatin M Receptor beta Subunit/genetics/metabolism ; Prognosis ; Signal Transduction ; Tumor Microenvironment ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a serious problem for patients as it metastasizes, decreasing 5-year patient survival from > 95 to ~ 27%. The breast tumor microenvironment (TME) is often saturated with proinflammatory cytokines, such as oncostatin M (OSM), which promote epithelial-to-mesenchymal transitions (EMT) in IDC and increased metastasis. The extracellular matrix (ECM) also plays an important role in promoting invasive and metastatic potential of IDC. Specifically, the reorganization and alignment of collagen fibers in stromal ECM leads to directed tumor cell motility, which promotes metastasis. Lysyl oxidase like-2 (LOXL2) catalyzes ECM remodeling by crosslinking of collagen I in the ECM. We propose a novel mechanism whereby OSM induces LOXL2 expression, mediating stromal ECM remodeling of the breast TME.

METHODS: Bioinformatics was utilized to determine survival and gene correlation in patients. IDC cell lines were treated with OSM (also IL-6, LIF, and IL-1β) and analyzed for LOXL2 expression by qRT-PCR and immunolabelling techniques. Collagen I contraction assays, 3D invasion assays, and confocal microscopy were performed with and without LOXL2 inhibition to determine the impact of OSM-induced LOXL2 on the ECM.

RESULTS: Our studies demonstrate that IDC patients with high LOXL2 and OSM co-expression had worse rates of metastasis-free survival than those with high levels of either, individually, and LOXL2 expression is positively correlated to OSM/OSM receptor (OSMR) expression in IDC patients. Furthermore, human IDC cells treated with OSM resulted in a significant increase in LOXL2 mRNA, which led to upregulated protein expression of secreted, glycosylated, and enzymatically active LOXL2. The expression of LOXL2 in IDC cells did not affect OSM-promoted EMT, and LOXL2 was localized to the cytoplasm and/or secreted. OSM-induced LOXL2 promoted an increase in ECM collagen I fiber crosslinking, which led to significant fiber alignment between cells and increased IDC cell invasion.

CONCLUSIONS: Aligned collagen fibers in the ECM provide pathways for tumor cells to migrate more easily through the stroma to nearby vasculature and tissue. These results provide a new paradigm through which proinflammatory cytokine OSM promotes tumor progression. Understanding the nuances in IDC metastasis will lead to better potential therapeutics to combat against the possibility.}, } @article {pmid34009452, year = {2021}, author = {Kusafuka, K and Ito, I and Hirata, K and Miyamoto, K and Shimizu, T and Satomi, H and Inagaki, H and Suzuki, M}, title = {A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.}, journal = {Medical molecular morphology}, volume = {54}, number = {3}, pages = {281-288}, pmid = {34009452}, issn = {1860-1499}, mesh = {Asian People ; Biomarkers, Tumor/analysis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/surgery ; ErbB Receptors/analysis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Japan ; Keratin-19/analysis/genetics ; Keratin-5/analysis/genetics ; Keratin-6/analysis/genetics ; Lip/surgery ; Lip Neoplasms/*diagnosis/metabolism/surgery ; Middle Aged ; Receptors, Androgen/analysis/genetics ; SOXE Transcription Factors/analysis/genetics ; }, abstract = {Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.}, } @article {pmid34007008, year = {2021}, author = {Liu, X and Huang, X and Bai, Y and Zhang, Z and Jin, T and Wu, H and Liang, Z}, title = {Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast.}, journal = {NPJ precision oncology}, volume = {5}, number = {1}, pages = {42}, pmid = {34007008}, issn = {2397-768X}, support = {2016-I2M-1-002//Chinese Academy of Medical Sciences (CAMS)/ ; 2019-I2M-2-002//Chinese Academy of Medical Sciences (CAMS)/ ; }, abstract = {Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of tumor. To date, the genetic abnormalities underlying EPC remain elusive. The purpose of this study was to gain further insight into EPC mutation profile. Forty-one EPCs diagnosed from 2015 to 2018 were included. Twenty-six EPCs were submitted to whole-exome sequencing (WES), and a 185 gene-targeted sequencing panel was designed to validate the results of the 26 EPCs that underwent WES and 15 additional cases. Recurrently mutated genes were further confirmed by Sanger sequencing. Our study revealed multiple recurrently mutated genes including PI3K-AKT-mTOR pathway genes (PIK3CA, AKT1, ULK1, MAP3K1, MAP2K4, RHOA, and PTEN) (27/41, 65.8%) and chromatin modification genes (ZFPM1, GATA3, CTCF, and KMT2C) (21/41, 51.2%) in EPC. Importantly, somatic ZFPM1 mutations existed in 9/41 (21.9%) of the EPCs. The frequency of ZFPM1 mutations in the EPCs was significantly higher than that of other tumor types. Of the nine ZFPM1 mutations, seven were frameshift mutations, and the remaining two were nonsense mutations. Moreover, a significant concurrence of ZFPM1 and PI3K-AKT-mTOR mutations were revealed in the EPCs. Of note, no TP53 mutations were detected in our EPCs, whereas it was detected in a considerable proportion of the luminal A invasive ductal carcinomas of no special type (IDC-NSTs) from TCGA. We reveal that recurrent somatic ZFPM1 mutation is characteristic of EPC and concurred with mutations in the PI3K-AKT-mTOR pathway. The distinctive genetic features of EPC might underlie its special histological structures and indolent behavior.}, } @article {pmid34002584, year = {2021}, author = {Lei, S and Zheng, R and Zhang, S and Chen, R and Wang, S and Sun, K and Zeng, H and Wei, W and He, J}, title = {Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030.}, journal = {Cancer biology & medicine}, volume = {18}, number = {3}, pages = {900-909}, pmid = {34002584}, issn = {2095-3941}, support = {2018-I2M-3-003//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2018YFC1315305//National Key Research and Development Program of China/ ; }, abstract = {OBJECTIVE: Breast cancer was the most common cancer and the fifth cause of cancer deaths among women in China in 2015. The evaluation of the long-term incidence and mortality trends and the prediction of the future burden of breast cancer could provide valuable information for developing prevention and control strategies.

METHODS: The burden of breast cancer in China in 2015 was estimated by using qualified data from 368 cancer registries from the National Central Cancer Registry. Incident cases and deaths in 22 cancer registries were used to assess the time trends from 2000 to 2015. A Bayesian age-period-cohort model was used to project the burden of breast cancer to 2030.

RESULTS: Approximately 303,600 new cases of breast cancer (205,100 from urban areas and 98,500 from rural areas) and 70,400 breast cancer deaths (45,100 from urban areas and 24,500 from rural areas) occurred in China in 2015. Urban regions of China had the highest incidence and mortality rates. The most common histological subtype of breast cancer was invasive ductal carcinoma, followed by invasive lobular carcinoma. The age-standardized incidence and mortality rates increased by 3.3% and 1.0% per year during 2000-2015, and were projected to increase by more than 11% until 2030. Changes in risk and demographic factors between 2015 and 2030 in cases are predicted to increase by approximately 13.3% and 22.9%, whereas deaths are predicted to increase by 13.1% and 40.9%, respectively.

CONCLUSIONS: The incidence and mortality of breast cancer continue to increase in China. There are no signs that this trend will stop by 2030, particularly in rural areas. Effective breast cancer prevention strategies are therefore urgently needed in China.}, } @article {pmid34001921, year = {2021}, author = {Hosio, M and Urpilainen, E and Hautakoski, A and Marttila, M and Arffman, M and Sund, R and Ahtikoski, A and Puistola, U and Läärä, E and Karihtala, P and Jukkola, A}, title = {Association of antidiabetic medication and statins with survival from ductal and lobular breast carcinoma in women with type 2 diabetes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {10445}, pmid = {34001921}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/complications/*mortality/therapy ; Carcinoma, Ductal, Breast/complications/*mortality/therapy ; Carcinoma, Lobular/complications/*mortality/therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypoglycemic Agents/*therapeutic use ; Middle Aged ; Prognosis ; Registries/statistics & numerical data ; Survival Analysis ; }, abstract = {We investigated the survival of female patients with pre-existing type 2 diabetes (T2D) diagnosed with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of breast, in relation to the use of metformin, other antidiabetic medication (ADM) and statins. The study cohort consisted of 3,165 women (2,604 with IDC and 561 with ILC). The cumulative mortality from breast cancer (BC) and from other causes was calculated using the Aalen-Johansen estimator. The cause-specific mortality rates were analysed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of different medications. No evidence of an association of metformin use with BC mortality was observed in either IDC (HR 0.92, 95% confidence interval [CI] 0.64-1.31) or ILC (HR 0.68, 95% CI 0.32-1.46) patients, when compared to other oral ADMs. The mortality from other causes was found to be lower amongst the IDC patients using metformin (HR 0.64, 95% CI 0.45-0.89), but amongst ILC patients the evidence was inconclusive (HR 1.22, 95% CI 0.64-2.32). Statin use was consistently associated with reduced mortality from BC in IDC patients (HR 0.77, 95% CI 0.62-0.96) and ILC patients (HR 0.59, 95% CI 0.37-0.96), and also mortality from other causes in IDC patients (HR 0.81, 95% CI 0.67-0.96) and in ILC patients (HR 0.66, 95% CI 0.43-1.01). We found no sufficient evidence for the possible effects of metformin and statins on the prognosis of BC being different in the two histological subtypes.}, } @article {pmid34001333, year = {2022}, author = {Cheng, D and Baynosa, J and Cross, C and Kirgan, D and Williams, SJ and St Hill, C}, title = {Comparing the effect of distance to treatment facility on reconstruction and breast conservation therapy for early-stage invasive ductal carcinoma between the nation and the mountain region.}, journal = {American journal of surgery}, volume = {224}, number = {4}, pages = {1049-1056}, doi = {10.1016/j.amjsurg.2021.04.024}, pmid = {34001333}, issn = {1879-1883}, mesh = {*Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Logistic Models ; *Mammaplasty ; Mastectomy ; Mastectomy, Segmental ; }, abstract = {BACKGROUND: Our objective is to evaluate the effect of distance to facility on the use of breast conservation therapy and reconstruction for early stage breast cancer.

METHODS: Utilizing the National Cancer Database, we identified females, age <65, with Stage I invasive ductal carcinoma from 2004 to 2015. Using logistic regression, we compared radiation, mastectomy, and reconstruction treatment patterns. A subgroup analysis was performed within the mountain region (MR).

RESULTS: Nationwide, there are decreasing odds of radiation, increasing odds of mastectomy, and increasing odds of reconstruction. Patients living farther were less likely to receive radiation, more likely to undergo mastectomy, with no effect on reconstruction. Within the MR, patients living farther from their facility were less likely to receive radiation, more likely to undergo mastectomy, however, they were less likely to undergo reconstruction.

CONCLUSIONS: Nationwide and within the MR, patients living farther from their facility are less likely to receive radiation and more likely to undergo mastectomy. There is a disparity between the MR and the nation in use of reconstruction for this population.}, } @article {pmid33998215, year = {2021}, author = {Song, D and Li, Z and Zhou, X and Zhang, Y and Feng, G and Zhou, B and Lü, C and Wu, P and Tang, Y and Yi, L and Luo, Z}, title = {[Muscle-sparing rectus abdominis myocutaneous flap vascularized with intercostal artery perforator and inferior epigastric artery perforator for breast reconstruction].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {35}, number = {5}, pages = {605-610}, pmid = {33998215}, issn = {1002-1892}, mesh = {Adult ; Epigastric Arteries/surgery ; Humans ; *Mammaplasty ; Middle Aged ; *Myocutaneous Flap ; Neoplasm Recurrence, Local ; *Perforator Flap ; Rectus Abdominis/transplantation ; }, abstract = {OBJECTIVE: To explore the surgical technique, effectiveness, and safety of muscle-sparing rectus abdominis myocutaneous flap vascularized with intercostal artery perforator and inferior epigastric artery perforator for breast reconstruction.

METHODS: Between December 2016 and February 2019, 6 cases of early breast cancer received modified radical surgery, lower abdominal flap was applied for one- or two-staged breast reconstruction. The average age of the patients was 34.6 years (range, 29-56 years). The disease duration ranged from 2 to 16 months, with an average of 9.5 months. The tumor was located in the upper outer quadrant in 4 cases and the lower outer quadrant in 2 cases. Pathological examination showed that they were all invasive ductal carcinoma. Four cases of breast cancer were in stage Ⅰ and 2 cases was in stage Ⅱ. During operation, the inferior epigastric artery perforators were found to be close to the upper edge of the flap and/or near the umbilical cord in 4 cases, the inferior epigastric artery perforator vessels were relatively small (<0.3 mm) in 2 cases; and the breast was reconstructed with muscle-sparing rectus abdominis myocutaneous flap vascularized with intercostal artery perforator and inferior epigastric artery perforator. The length, width, and thickness of the flap were (28.9±0.2), (12.1±0.4), and (4.4±0.3) cm, respectively. The length of the vascular pedicle was (11.5±0.2) cm and the weight of the flap was (420.5±32.7) g.

RESULTS: All 6 muscle-sparing rectus abdominis myocutaneous flaps were successful, and the breast incisions healed by first intention. There was no vascular crisis, donor site effusion, hematoma, or infection. All 6 patients were followed up 12-36 months (mean, 26.8 months). The reconstructed breast had a good shape, good elasticity, and no flap contracture or deformation; only linear scars left at the donor site of the flap, and the abdominal wall function was not affected. During follow-up, there was no breast cancer recurrence and metastasis.

CONCLUSION: When the inferior epigastric artery perforators are too close to the upper edge of the flap and/or near the umbilical cord, the vascularity of lower abdominal flap can be ruined, harvested in form of muscle-sparing rectus abdominis myocutaneous flap vascularized with intercostal artery perforator and inferior epigastric artery perforator can efficiently ensure blood supply safety.}, } @article {pmid33997437, year = {2021}, author = {Lee, CP and Hoo, JY and Hashimoto, M}, title = {Effect of Oil Content on the Printability of Coconut Cream.}, journal = {International journal of bioprinting}, volume = {7}, number = {2}, pages = {354}, pmid = {33997437}, issn = {2424-8002}, abstract = {We developed a method to perform direct ink writing (DIW) three-dimensional (3D) printing of coconut-based products with high oil content by varying compositions of the coconut oil and the coconut cream. The addition of oils is particularly crucial in providing energy, developing neurological functions, and improving the palatability of food. Despite the potential merits of high oil-content foods, there have been limited studies on 3D printing of high oil-content foods. In particular, the effect of oil content on the printability of food inks has not been studied to date. 3D printing of food inks with high oil contents is challenging due to oil separation that leads to unpredictable changes in rheological properties. In this work, we surveyed the behavior of the mixture of the coconut oil and the coconut cream and identified the appropriate conditions for the food inks that show the printability in DIW 3D printing. We initially formulated coconut cream inks added with coconut oil that did not exhibit oil separation, and characterized the rheological properties of such inks. We successfully 3D-printed coconut cream with additional coconut oil and successfully fabricated 3D structures with inks containing 25% water with an additional 10% (w/w) of coconut oil. Texture profile analysis (TPA) suggested that the hardness index and the chewiness index of mesh-shaped 3D-printed coconut cream decreased due to an increase in the water content of the ink. Overall, this study offered an understanding of the stability of the food inks and demonstrated the fabrication of 3D colloidal food with controlled oil content, which can be applied to formulating foods with tunable oil content to cater to individual nutritional needs without compromising the stability of the inks.}, } @article {pmid33996360, year = {2021}, author = {Salemis, NS}, title = {Synchronous occurrence of breast cancer and refractory diffuse large B-cell abdominal lymphoma: Management and review of the literature.}, journal = {Intractable & rare diseases research}, volume = {10}, number = {2}, pages = {131-135}, pmid = {33996360}, issn = {2186-3644}, abstract = {The synchronous occurrence of primary breast cancer and lymphoid tissue malignant tumors has been rarely reported in the literature. We present an exceedingly rare case of synchronous breast invasive ductal carcinoma with an abdominal diffuse large B-cell lymphoma (DLBCL). A 78-year-old woman who was diagnosed with a luminal A invasive breast cancer on core biopsy, and complaint of progressively worsening low back pain. An abdominal computed tomography (CT) scan that was performed as part of the preoperative staging showed a large abdominal mass measuring 10.5 × 4.8 × 9.5 cm surrounding the lower part of the abdominal aorta, the right common iliac, right external, right internal iliac, and the left internal iliac arteries. A CT-guided fine-needle aspiration biopsy (FNAB) of the abdominal mass was then performed, to exclude the possibility of being an abdominal tumor metastasis of the known primary breast cancer. Histopathological findings were suggestive of DLBCL. Following a multidisciplinary team discussion, chemotherapy was initiated for DLBCL. The tumor however was refractory to multiple chemotherapy regimens and exhibited a highly aggressive clinical course. The diagnostic evaluation and management of the patient are discussed, along with a review of the relevant literature. This case underscores the fact that the presence of synchronous malignancies may pose both diagnostic and treatment challenges. Accurate staging of both malignancies and multidisciplinary team discussion is of utmost importance to guide an optimal therapeutic approach. Histopathological evaluation is essential for both tumors, for the second malignancy not to be misinterpreted as a secondary deposit of the primary one.}, } @article {pmid33995786, year = {2021}, author = {Hajji, A and Mhabrech, HE and Daldoul, A and Toumia, N and Hajjaji, A and Njima, M and Jebali, F and Faleh, R}, title = {[Breast cancer and pregnancy: about 15 cases collected at the maternity center Monastir, Tunisia].}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {180}, pmid = {33995786}, issn = {1937-8688}, mesh = {Adult ; Age Factors ; Breast Neoplasms/diagnosis/*pathology/therapy ; Carcinoma/diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*pathology/therapy ; Female ; Humans ; Neoplasm Staging ; Postpartum Period ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/*pathology/therapy ; Prognosis ; Retrospective Studies ; Survival Rate ; Tunisia ; }, abstract = {The purpose of this study was to describe the clinical, radiological, histological and therapeutic features of breast cancer diagnosed during pregnancy. We performed a review of all medical records of patients with breast cancer diagnosed during pregnancy in the Maternity and Neonatal Center, Monastir-Tunisia, over the period 2004-2019. We collected data on 15 cases. The average age of patients was 34 years; most pregnancy-associated breast cancers (PABCs) had been diagnosed during the postpartum period. Invasive ductal carcinoma was the major histological type (93% of cases), a rare case of secretory breast carcinoma had been observed. The main clinical stages were T2 and T4 breast cancer. Hormone receptor (HR)-negative breast cancers had been reported in 40% of cases, HER2-positive breast cancers in 26.6% of cases. Treatment included surgery, radiotherapy, chemotherapy and palliative chemotherapy. The median overall survival was 32.2 months. Pregnancy-associated breast cancer is a rare entity. Patients' prognosis is generally poor due to the young age at onset and a usually delayed diagnosis. Patients should participate in therapeutic decision making, which is difficult and multidisciplinary. Targeted therapy is the great hope for new therapies.}, } @article {pmid33987039, year = {2021}, author = {Haroon, S and Zia, S and Shirazi, UA and Ahmed, O and Asghar, IA and Diwan, MA and Afzal, A and Irfan, M and Ali, SJ and Hashmi, AA}, title = {Metaplastic Breast Carcinoma: Clinicopathological Parameters and Prognostic Profile.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14347}, pmid = {33987039}, issn = {2168-8184}, abstract = {Introduction Metaplastic breast carcinoma (MBC) is defined as breast cancer with a heterologous non-glandular component. MBC is considered a special type of breast cancer with a prognosis that is worse than invasive ductal carcinoma (IDC) of the breast. MBC is the most common breast cancer with a triple-negative profile. Therefore, in this study, we evaluated the clinicopathological parameters, recurrence and survival of MBC in our population. Methods We conducted a retrospective observational study in the Department of Histopathology at Prince Faisal Oncology Centre, Buraidah, Saudi Arabia, over a period of five years. All cases diagnosed as MBC were included in the study. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) immunohistochemistry (IHC) was performed on representative tissue blocks. Results Total 183 cases of MBCs were included in the study, out of which 120 cases were excision specimens. The mean age of the patients was 48.84±12.99 years, and the most common age group was between 36 and 50 years of age. Most of the cases were tumor (T) stage T3 (50%), and nodal metastasis was present in 40% of cases. Most cases were grade III (78.7%). ER, PR and HER2/neu positivity was noted in 15.8%, 13.1%, and 9.8% cases, respectively. Follow-up data were available for 70 cases, with a median follow-up period of 4 (1-7) years. Tumor recurrence was noted in 31.4% cases, with a survival rate of 71.4%. Squamous, chondroid, spindle cell differentiation, and matrix production were noted in 70.5%, 7.1%, 13.7%, and 2.2% cases, respectively. A significant association of squamous differentiation was noted with HER2/neu positivity. An inverse association of spindle cell differentiation was seen with axillary metastasis. Survival analysis by Kaplan-Meier revealed a significant association of survival with tumor recurrence. Conclusion MBC is an important subtype of breast cancer, histopathological identification of which is challenging, owing to varied histological differentiation. We found squamous differentiation to be the most common in MBC, which was associated with HER2/neu positivity. A high recurrence rate of MBC was also observed in our study that was significantly associated with survival.}, } @article {pmid33983449, year = {2022}, author = {March, DS and Lai, KB and Neal, T and Graham-Brown, MPM and Highton, PJ and Churchward, DR and Young, HML and Dungey, M and Stensel, DJ and Smith, AC and Bishop, NC and Szeto, CC and Burton, JO}, title = {Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {2}, pages = {366-374}, doi = {10.1093/ndt/gfab178}, pmid = {33983449}, issn = {1460-2385}, mesh = {*Endotoxins ; Exercise ; Humans ; Inflammation/etiology ; Physical Fitness ; *Renal Dialysis/adverse effects ; }, abstract = {BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.

METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months.

RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio.

CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.}, } @article {pmid33977328, year = {2021}, author = {Iezzi, R and Campenni, P and Posa, A and Parello, A and Rodolfino, E and Marra, AA and Ratto, C and Manfredi, R}, title = {Outpatient Transradial Emborrhoid Technique: A Pilot Study.}, journal = {Cardiovascular and interventional radiology}, volume = {44}, number = {8}, pages = {1300-1306}, pmid = {33977328}, issn = {1432-086X}, mesh = {Aged ; Embolization, Therapeutic/*methods ; Female ; Hemorrhoids/*therapy ; Humans ; Male ; *Outpatients ; Pilot Projects ; Prospective Studies ; Rectum/blood supply ; Treatment Outcome ; }, abstract = {PURPOSE: To determine whether outpatient transradial emborrhoid technique can be performed safely and effectively in the treatment of symptomatic hemorrhoids.

MATERIALS AND METHODS: The transradial emborrhoid technique was used to treat 12 patients with symptomatic hemorrhoids in an outpatient setting during a 4-month period. After percutaneous catheterization of the left radial artery, a 5-Fr sheath was introduced to catheterize the inferior mesenteric artery and a microcatheter was advanced into the branches of the superior rectal artery for embolization with 0.018-inch detachable coils (Interlock and IDC-interlocking detachable coils). After embolization, the sheath was withdrawn and puncture site hemostasis was achieved using a wrist band. All patients were evaluated 6 h after the procedure to determine whether they meet the discharge criteria and were discharged the following day. The results of the emborrhoid treatment were assessed at the 4-week follow-up.

RESULTS: The emborrhoid technique was successful in all patients. There was no major complication associated with the procedure. All patients met the discharge criteria 6 h after the procedure. Reduction of local edema and of hemorrhoidal congestion was observed in all patients. At the follow-up visit, the mean Rorvik score (HDSS + SHS-HD) decreased from 31.50 (7.50) to 13.11 (8.33) (p < .001).

CONCLUSIONS: Transradial rectal artery embolization is a safe and effective treatment option for patients with chronic symptoms of hemorrhoid disease.}, } @article {pmid33975551, year = {2021}, author = {Zhou, X and Zheng, Z and Li, Y and Zhao, W and Lin, Y and Zhang, J and Sun, Q}, title = {The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {536}, pmid = {33975551}, issn = {1471-2407}, mesh = {Adenocarcinoma, Mucinous/*mortality/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: At present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test.

RESULTS: From 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5-/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238-2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330-2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334-0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552-0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288-0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459-0.756, P < 0.001) were identified as protective factors.

CONCLUSION: Compared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.}, } @article {pmid33973829, year = {2022}, author = {Hanfee, AR and Ghazi, KR and Ashfaq, Z and Kayani, N and Din, NU}, title = {Primary Follicular Dendritic Cell Sarcoma of Breast: 2 Further Cases with Review of the Literature.}, journal = {International journal of surgical pathology}, volume = {30}, number = {1}, pages = {55-62}, doi = {10.1177/10668969211017317}, pmid = {33973829}, issn = {1940-2465}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/diagnosis/metabolism/*pathology ; Dendritic Cell Sarcoma, Follicular/diagnosis/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; }, abstract = {Follicular dendritic cell sarcoma (FDCS) is a tumor derived from antigen-presenting cells and can occur within lymphoid tissue or at extranodal sites. FDCS of the breast is remarkably rare, with only 4 cases previously reported in literature. FDCS appears grossly as a well-circumscribed, firm mass with a grey-yellow surface, areas of necrosis, and histologically comprises of spindled, oval, or epithelioid cells with intensely eosinophilic cytoplasm. Immunohistochemistry plays a key role in its diagnosis. Here we describe 2 cases of FDCS of breast in 2 women aged 70 and 35 years old, who presented with a palpable lump in the breast. One patient had concomitant invasive ductal carcinoma as well. We highlight the key histopathological and immunohistochemical features of the tumor.}, } @article {pmid33970384, year = {2021}, author = {Ramadan, A and Hashim, M and Abouzid, A and Swellam, M}, title = {Clinical impact of PTEN methylation status as a prognostic marker for breast cancer.}, journal = {Journal, genetic engineering & biotechnology}, volume = {19}, number = {1}, pages = {66}, pmid = {33970384}, issn = {2090-5920}, abstract = {BACKGROUND: Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0-I, n = 48) and late stage (II-III, n = 64), and graded into low grade (I-II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method.

RESULTS: The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up.

CONCLUSIONS: PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.}, } @article {pmid33966784, year = {2021}, author = {Weinstein, G}, title = {Coincidence and reproducibility in the EHT black hole experiment.}, journal = {Studies in history and philosophy of science}, volume = {85}, number = {}, pages = {63-78}, doi = {10.1016/j.shpsa.2020.09.007}, pmid = {33966784}, issn = {0039-3681}, mesh = {Knowledge ; Philosophy/history ; Reproducibility of Results ; *Telescopes ; }, abstract = {This paper discusses some philosophical aspects related to the recent publication of the experimental results of the 2017 black hole experiment, namely the first image of the supermassive black hole at the center of galaxy M87. In this paper I present a philosophical analysis of the 2017 Event Horizon Telescope (EHT) black hole experiment. I first present Hacking's philosophy of experimentation. Hacking gives his taxonomy of elements of laboratory science and distinguishes a list of elements. I show that the EHT experiment conforms to major elements from Hacking's list. I then describe with the help of Galison's Philosophy of the Shadow how the EHT Collaboration created the famous black hole image. Galison outlines three stages for the reconstruction of the black hole image: Socio-Epistemology, Mechanical Objectivity, after which there is an additional Socio-Epistemology stage. I subsequently present my own interpretation of the reconstruction of the black hole image and I discuss model fitting to data. I suggest that the main method used by the EHT Collaboration to assure trust in the results of the EHT experiment is what philosophers call the Argument from Coincidence. I show that using this method for the above purpose is problematic. I present two versions of the Argument from Coincidence: Hacking's Coincidence and Cartwright's Reproducibility by which I analyse the EHT experiment. The same estimation of the mass of the black hole is reproduced in four different procedures. The EHT Collaboration concludes: the value we have converged upon is robust. I analyse the mass measurements of the black hole with the help of Cartwright's notion of robustness. I show that the EHT Collaboration construe Coincidence/Reproducibility as Technological Agnosticism and I contrast this interpretation with van Fraassen's scientific agnosticism.}, } @article {pmid33966256, year = {2021}, author = {Tsokanos, FF and Muley, C and Khani, S and Hass, D and Fleming, T and Wolff, G and Bartelt, A and Nawroth, P and Herzig, S}, title = {Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.}, journal = {Thrombosis and haemostasis}, volume = {121}, number = {11}, pages = {1464-1475}, doi = {10.1055/s-0041-1726346}, pmid = {33966256}, issn = {2567-689X}, support = {Deutsche Forschungsgemeinschaft//SFB1118/ ; }, mesh = {Animals ; Cells, Cultured ; Gene Expression Profiling ; Glycolysis/*drug effects ; Macrophage Activation/*drug effects ; Macrophages/*drug effects/immunology/metabolism ; Mice ; Phenotype ; Phosphorylation ; Pyruvaldehyde/*toxicity ; Signal Transduction ; Transcriptome ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.}, } @article {pmid33964737, year = {2021}, author = {Choudhary, T and Mishra, V and Goswami, A and Sarangapani, J}, title = {A transfer learning with structured filter pruning approach for improved breast cancer classification on point-of-care devices.}, journal = {Computers in biology and medicine}, volume = {134}, number = {}, pages = {104432}, doi = {10.1016/j.compbiomed.2021.104432}, pmid = {33964737}, issn = {1879-0534}, mesh = {*Breast Neoplasms ; Female ; Humans ; Machine Learning ; Neural Networks, Computer ; Point-of-Care Systems ; }, abstract = {BACKGROUND AND OBJECTIVE: A significant progress has been made in automated medical diagnosis with the advent of deep learning methods in recent years. However, deploying a deep learning model for mobile and small-scale, low-cost devices is a major bottleneck. Further, breast cancer is more prevalent currently, and ductal carcinoma being its most common type. Although many machine/deep learning methods have already been investigated, still, there is a need for further improvement.

METHOD: This paper proposes a novel deep convolutional neural network (CNN) based transfer learning approach complemented with structured filter pruning for histopathological image classification, and to bring down the run-time resource requirement of the trained deep learning models. In the proposed method, first, the less important filters are pruned from the convolutional layers and then the pruned models are trained on the histopathological image dataset.

RESULTS: We performed extensive experiments using three popular pre-trained CNNs, VGG19, ResNet34, and ResNet50. With VGG19 pruned model, we achieved an accuracy of 91.25% outperforming earlier methods on the same dataset and architecture while reducing 63.46% FLOPs. Whereas, with the ResNet34 pruned model, the accuracy increases to 91.80% with 40.63% fewer FLOPs. Moreover, with the ResNet50 model, we achieved an accuracy of 92.07% with 30.97% less FLOPs.

CONCLUSION: The experimental results reveal that the pre-trained model's performance complemented with filter pruning exceeds original pre-trained models. Another important outcome of the research is that the pruned model with reduced resource requirements can be deployed in point-of-care devices for automated diagnosis applications with ease.}, } @article {pmid33962262, year = {2021}, author = {Salih, AM and Hammood, ZD and Hassan, MN and Baba, HO and Muhialdeen, AS and Abdullah, IY and Abdulla, BA and Kakamad, FH and Mustafa, SM and Mohammed, SH and Mustafa, MQ}, title = {Breast cancer metastasizing to the contralateral axilla several years after treatment: A case report with literature review.}, journal = {International journal of surgery case reports}, volume = {82}, number = {}, pages = {105900}, pmid = {33962262}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Lymph node metastasis is the most prominent prognostic factor in breast cancer. The aim of this paper is to report a case of contralateral axillary lymph node metastasis (CAM) which look like metachronous initially, but histopathologicaly confirmed as synchronous CAM.

CASE PRESENTATION: A-44-year old female was a known case of left breast cancer five years prior to this presentation (T2,N2,M0, grade III, Triple negative, multifocal invasive ductal carcinoma). On follow up, multiple contralateral axillary suspicious lymph nodes were discovered. Fine Needle Aspiration Cytology from the lesion revealed grade III, Triple negative, invasive ductal carcinoma consistent with metastasis from the left invasive ductal carcinoma. Bilateral mastectomy and right axillary dissection were performed. The histopathological examination and immunohistochemistry showed left breast recurrent 0.5 cm grade III, Triple negative invasive ductal carcinoma.

DISCUSSION: If a cancer is found in the contralateral axilla, three main potential sources should be considered: contralateral spread from the original breast tumor, metastasis from an occult primary in the ipsilateral breast, and metastasis from an extramammary site.

CONCLUSION: Although CAM in patients with breast cancer is an uncommon condition, it is still possible to occur. There is a controversy regarding the appropriate management.}, } @article {pmid33960872, year = {2021}, author = {Alvarez, DR and Ospina, A and Barwell, T and Zheng, B and Dey, A and Li, C and Basu, S and Shi, X and Kadri, S and Chakrabarti, K}, title = {The RNA structurome in the asexual blood stages of malaria pathogen plasmodium falciparum.}, journal = {RNA biology}, volume = {18}, number = {12}, pages = {2480-2497}, pmid = {33960872}, issn = {1555-8584}, mesh = {Erythrocytes/*metabolism ; *Gene Expression Regulation ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*parasitology ; *Nucleic Acid Conformation ; Plasmodium falciparum/*genetics/growth & development/pathogenicity ; Protozoan Proteins/genetics/metabolism ; RNA, Protozoan/*chemistry ; Transcriptome ; }, abstract = {Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and non-coding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, ApiAP2, DNA-/RNA-binding protein, Alba3 and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in P. falciparum. Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs. Abbreviations: CDS: Coding Sequence; DNA: Deoxyribonucleic Acid; dsRNA: double-stranded RNA; IDC: Intra-erythrocytic Developmental Cycle (IDC); m6A: N6-methyladenosine; mRNA: Messenger RNA; ncRNA: Non-coding RNA; RBC: Red Blood cells; RBP: RNA-Binding Protein; REC: Relative Expression Counts; RNA-seq: RNA-sequencing; RNA: Ribonucleic Acid; RNP: Ribonucleoprotein; RPKM: Reads Per Kilobase of transcript Per Million; rRNA: Ribosomal RNA 16. RUFs: RNAs of Unknown Function; SHAPE: Selective 2'-hydroxyl acylation analysed by primer extension; snoRNA: Small Nucleolar RNA; snRNA: Small Nuclear RNA; SRP-RNA: Signal Recognition Particle RNA; ssRNA: (Single-stranded RNA); TE: Translation Efficiency; tRNA: transfer RNA; UTR: Untranslated Region.}, } @article {pmid33947745, year = {2021}, author = {Sottnik, JL and Bordeaux, EK and Mehrotra, S and Ferrara, SE and Goodspeed, AE and Costello, JC and Sikora, MJ}, title = {Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {8}, pages = {1270-1282}, pmid = {33947745}, issn = {1557-3125}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; R00 CA193734/CA/NCI NIH HHS/United States ; T32 GM007635/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Breast/pathology ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Lobular/drug therapy/*genetics/pathology ; Cell Cycle Proteins/*genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; MCF-7 Cells ; Promoter Regions, Genetic/drug effects/genetics ; Receptors, Estrogen/*genetics ; Signal Transduction/genetics ; Tamoxifen/therapeutic use ; Transcriptome/drug effects/genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER[+] ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER[+] invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER[+] ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.}, } @article {pmid33945869, year = {2021}, author = {Sethy, C and Goutam, K and Das, B and Dash, SR and Kundu, CN}, title = {Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis.}, journal = {Vascular pharmacology}, volume = {140}, number = {}, pages = {106865}, doi = {10.1016/j.vph.2021.106865}, pmid = {33945869}, issn = {1879-3649}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; *Cell Adhesion Molecules/metabolism ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; *Nectins/metabolism ; *Receptors, CXCR4/metabolism ; *Vesicular Transport Proteins/metabolism ; }, abstract = {Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD). LVD was significantly higher in axillary lymph node (ALN) than primary tumor. Depleting Nectin-4, VEGF-C or both attenuated the important lymphangiogenic marker LYVE-1 expression, tube formation, and migration of ALN derived primary cells. Nectin-4 stimulated the expressions of CXCR4 and CXCL12 under hypoxic conditions in ALN derived primary cells. Further, Nectin-4 augmented expressions of lymphatic metastatic markers (e.g. eNOS, TGF-β, CD-105) and MMPs. Induced expressions of Nectin-4 along with other representative metastatic markers were noted in lymph and blood circulating tumor cells (LCTCs and BCTCs) of local and distant metastatic samples. Thus, Nectin-4 displayed a predominant role in promoting tumor-induced lymphangiogenesis and lymphatic metastasis by modulating CXCR4/CXCL12-LYVE-1- axis.}, } @article {pmid33945680, year = {2021}, author = {Soussy, N and Dufayet, L and Ravault, E and Viron, S and Gorgiard, C and Fournier, L}, title = {Management of the COVID-19 epidemic in a French immigration detention center.}, journal = {International journal of prisoner health}, volume = {}, number = {}, pages = {}, doi = {10.1108/IJPH-05-2020-0035}, pmid = {33945680}, issn = {1744-9219}, abstract = {PURPOSE: The purpose of this paper is to give an overview of management of the COVID-19 epidemic in a French immigration detention center.

DESIGN/METHODOLOGY/APPROACH: During containment in France because of COVID-19, the judicial authorities had to deal with the risk of contamination within immigration detention centers (IDC). In the Paris IDC, which can usually receive up to 240 individuals, measures have been taken to limit the risk of contamination by releasing individuals without prior judicial conviction and testing the others by a nasal swab.

FINDINGS: The test was done for all the present individuals (48), except two who refused. Eight tests (17.4%) were positive and only one was symptomatic. Individuals testing positive for COVID-19 were transferred into COVID-centers specially created during this health crisis.

ORIGINALITY/VALUE: Management of the COVID-19 epidemic in this French IDC illustrates the necessity of good cooperation between judicial authorities and medical teams in charge of those centers and the difficulty of balancing public health actions with state security.}, } @article {pmid33937141, year = {2021}, author = {Groheux, D and Hindie, E}, title = {Breast cancer: initial workup and staging with FDG PET/CT.}, journal = {Clinical and translational imaging}, volume = {9}, number = {3}, pages = {221-231}, pmid = {33937141}, issn = {2281-5872}, abstract = {PURPOSE: Precise staging is needed to plan optimal management in breast cancer. 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG-PET/CT) offers high sensitivity in detecting extra axillary lymph nodes and distant metastases. This review aims to clarify in which groups of patients staging with FDG-PET/CT would be beneficial and should be offered. We also discuss how tumor biology and breast cancer subtypes should be taken into account when interpreting FDG-PET/CT scans.

METHODS: We performed a comprehensive literature review and rigorous appraisal of research studies assessing indications for FDG-PET/CT in breast cancer. This assessment regarding breast cancer served as a basis for the recommendations set by a working group of the French Society of Nuclear Medicine, in collaboration with oncological societies, for developing good clinical practice recommendations on the use of FDG-PET/CT in oncology.

RESULTS: FDG-PET/CT is useful for initial staging of breast cancer, independently of tumor phenotype (triple negative, luminal or HER2 +) and regardless of tumor grade. Considering histological subtype, FDG-PET/CT performs better for staging invasive ductal carcinoma, although it is also helpful for staging invasive lobular carcinomas. Based on the available data, FDG-PET/CT becomes useful for staging starting from clinical stage IIB. FDG-PET/CT is possibly useful in patients with clinical stage IIA (T1N1 or T2N0), but there is not enough strong data to recommend routine use in this subgroup. For clinical stage I (T1N0) patients, staging with FDG-PET/CT offers no added value.

CONCLUSION: FDG-PET/CT is useful for staging patients with breast cancer, starting from clinical stage IIB.}, } @article {pmid33936237, year = {2021}, author = {Felezi, S and Nosrati, A and Eslami Jouybari, M and Jafarshad, J}, title = {Interdigitating Dendritic Cell Tumor of Submandibular Lymph Node: Case Report and Literature Review.}, journal = {Iranian journal of pathology}, volume = {16}, number = {2}, pages = {237-242}, pmid = {33936237}, issn = {1735-5303}, abstract = {Dendritic cells (DCs) are key arms of immune system, which act in antigen presenting processes, and are considered as a bridge between innate and adaptive immune responses. DCs are found in both lymphoid and non-lymphoid organs. They are called interdigitating dendritic cells (IDCs) in secondary lymphoid organs. IDCs lack lineage surface markers and are positive for S-100 and vimentin. IDC sarcoma (IDCS) is a very rare neoplasm, which mainly affects lymph nodes, though there are reports of extra-nodal involvement. IDCS is thought to have poor prognosis. Although there is no consensus on the treatment modalities, such options as radical surgery, chemotherapy, and radiotherapy are performed depending on severity and site of the lesion. In this study, we present a case of IDCS in a 53-year-old male with a history of several skin lesions and prior diagnoses of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and metatypical carcinoma (MTC).}, } @article {pmid33930678, year = {2021}, author = {Solomon, Z and Ginzburg, K and Ohry, A and Mikulincer, M}, title = {Overwhelmed by the news: A longitudinal study of prior trauma, posttraumatic stress disorder trajectories, and news watching during the COVID-19 pandemic.}, journal = {Social science & medicine (1982)}, volume = {278}, number = {}, pages = {113956}, pmid = {33930678}, issn = {1873-5347}, mesh = {*COVID-19 ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Pandemics ; *Prisoners of War ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology/etiology ; *Veterans ; }, abstract = {RATIONALE: It has been recognized that exposure to mass trauma tends to increase the time spent watching television (TV) news. Yet, research on the effects of this tendency on individuals' well-being yielded inconclusive findings.

OBJECTIVE: The aim of this longitudinal study is to examine the effects of prior trauma and posttraumatic stress disorder (PTSD) on changes in the amount of TV news watching and its effect on subsequent PTSD. More specifically, we examined the interrelations of prior exposure to war captivity, long-term PTSD trajectories, and amount of change TV news watching with PTSD severity during the COVID-19 pandemic, among aging Israeli combat veterans.

METHODS: One-hundred-and-twenty Israeli ex-prisoners of war (ex-POWs) from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) were followed up at five points of time: 1991 (T1), 2003 (T2), 2008 (T3), 2015 (T4), and in April-May 2020 (T5), during the outbreak of the COVID-19 pandemic.

RESULTS: Ex-POWs had higher odds of COVID-19 related increase in TV news watching, which, in turn, contributed to PTSD severity at T5. In addition, delayed PTSD trajectory was associated with COVID-19 related increase in TV news watching, which, in turn, contributed to more severe PTSD at T5.

CONCLUSIONS: These findings highlight the negative implications of TV news watching during a mass trauma for traumatized individuals. More specifically, they demonstrate its potential pathogenic role in exacerbating prior PTSD among trauma survivors.}, } @article {pmid33927959, year = {2021}, author = {İyikesici, MS and Slocum, AK and Winters, N and Kalamian, M and Seyfried, TN}, title = {Metabolically Supported Chemotherapy for Managing End-Stage Breast Cancer: A Complete and Durable Response.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14686}, pmid = {33927959}, issn = {2168-8184}, abstract = {Breast cancer accounts for significant morbidity and mortality worldwide. Currently, treatment options in metastatic breast cancer consist of chemotherapy, along with endocrine, radiation, and/or biological therapies. Although advances in management have improved overall survival times, the treatment options for women with end-stage disease are mostly limited to supportive care. Herein, we present a case report that highlights the response of a 47-year-old premenopausal woman with end-stage (T4N3M1) breast cancer treated with metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT). The patient first noticed a right breast mass in late 2016, which was initially evaluated and ruled out as a cyst. Skin ulceration was observed in the region of the suspected cyst in May 2017. Subsequent bilateral breast ultrasound identified masses in both breasts and an enlarged right axillary lymph node. The diagnosis following biopsy was grade 3, estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2 negative (HER2-), invasive ductal carcinoma of the breast. Initially, the patient refused to receive conventional chemotherapy because of its potential for side effects and toxicity, but she sought medical treatment in August 2018 following extensive disease progression and deterioration of general health. On reevaluation, the patient was considered ineligible for conventional treatment due to her advanced end-stage disease, poor performance status (Eastern Cooperative Oncology Group score: 3), and advanced respiratory symptoms. Exploring other options, the patient was admitted to the ChemoThermia Oncology Center, Istanbul, Turkey in November 2018. At that time, the patient weighed 38 kg (body mass index: 18.1 kg/m[2]) and had extensive metastatic disease with lesions in the brain, lungs, mediastinum, liver, abdomen, and bones that were detected by magnetic resonance imaging of the brain (with contrast) and whole-body (18F)-fluorodeoxyglucose-positron emission tomography-computed tomography. The patient received a six-month treatment protocol comprised of MSCT, KD, HT, and HBOT, which eliminated all detectable lesions. The therapeutic response was sustained for two years with maintenance treatment comprising KD, dietary supplements, and repurposed medications. This single case report presents evidence of a complete and durable response to a treatment protocol combining MSCT and a novel metabolic therapy in a patient with end-stage breast cancer.}, } @article {pmid33927856, year = {2021}, author = {Leite, C and Dias, N and Oliveira, D and Mesquita Pinto, R and Cortez Vaz, F}, title = {Metaplastic breast cancer with chondroid differentiation-case report and literature review.}, journal = {Journal of surgical case reports}, volume = {2021}, number = {4}, pages = {rjab113}, pmid = {33927856}, issn = {2042-8812}, abstract = {Metaplastic breast cancer (MBC) comprises less than 1% of all breast cancers, and it is defined by a mixture of adenocarcinoma plus mesenchymal and epithelial components. It is more common in older and black female patients. It has a larger size and faster growth, and it is frequently node-negative and triple-negative when compared with invasive ductal carcinoma. The authors report the case of a 72-year-old female patient, presenting with a breast lump, whose biopsy revealed a probable MBC with chondroid differentiation. She underwent a breast conservative surgery (BCS) and axillary sentinel lymph node dissection (SLND). The pathological report was concordant with the biopsy, and the patient was proposed to chemoradiotherapy. Despite its rarity and more severe features at diagnosis, BCS plus SLND plus radiotherapy should be offered to these patients, associated with chemotherapy. Chondroid differentiation is the rarest of all histological subtypes.}, } @article {pmid33927317, year = {2021}, author = {Amboni, M and Ricciardi, C and Picillo, M and De Santis, C and Ricciardelli, G and Abate, F and Tepedino, MF and D'Addio, G and Cesarelli, G and Volpe, G and Calabrese, MC and Cesarelli, M and Barone, P}, title = {Gait analysis may distinguish progressive supranuclear palsy and Parkinson disease since the earliest stages.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {9297}, pmid = {33927317}, issn = {2045-2322}, mesh = {Aged ; Diagnosis, Differential ; Female ; *Gait Analysis ; Humans ; Logistic Models ; Male ; Middle Aged ; Parkinson Disease/*diagnosis/physiopathology ; Supranuclear Palsy, Progressive/*diagnosis/physiopathology ; }, abstract = {Progressive supranuclear palsy (PSP) is a rare and rapidly progressing atypical parkinsonism. Albeit existing clinical criteria for PSP have good specificity and sensitivity, there is a need for biomarkers able to capture early objective disease-specific abnormalities. This study aimed to identify gait patterns specifically associated with early PSP. The study population comprised 104 consecutively enrolled participants (83 PD and 21 PSP patients). Gait was investigated using a gait analysis system during normal gait and a cognitive dual task. Univariate statistical analysis and binary logistic regression were used to compare all PD patients and all PSP patients, as well as newly diagnosed PD and early PSP patients. Gait pattern was poorer in PSP patients than in PD patients, even from early stages. PSP patients exhibited reduced velocity and increased measures of dynamic instability when compared to PD patients. Application of predictive models to gait data revealed that PD gait pattern was typified by increased cadence and longer cycle length, whereas a longer stance phase characterized PSP patients in both mid and early disease stages. The present study demonstrates that quantitative gait evaluation clearly distinguishes PSP patients from PD patients since the earliest stages of disease. First, this might candidate gait analysis as a reliable biomarker in both clinical and research setting. Furthermore, our results may offer speculative clues for conceiving early disease-specific rehabilitation strategies.}, } @article {pmid33927073, year = {2021}, author = {Huang, X and Cai, S and Wu, P and Huang, S and Yao, M}, title = {Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {46}, number = {3}, pages = {263-271}, doi = {10.11817/j.issn.1672-7347.2021.190371}, pmid = {33927073}, issn = {1672-7347}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/diagnostic imaging/genetics ; Female ; Humans ; Receptor, ErbB-2/genetics ; Receptors, Estrogen ; Receptors, Progesterone ; X-Rays ; }, abstract = {OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer.

METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed.

RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively).

CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.}, } @article {pmid33922137, year = {2021}, author = {Lin, IH and Kuo, BI and Liu, FY}, title = {Adjuvant Intravitreal Bevacizumab Injection for Choroidal and Orbital Metastases of Refractory Invasive Ductal Carcinoma of the Breast.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {5}, pages = {}, pmid = {33922137}, issn = {1648-9144}, mesh = {*Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; *Carcinoma, Ductal/drug therapy ; Female ; Humans ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence ; }, abstract = {The efficacy of combined intravitreal bevacizumab injection with systemic chemotherapy, palliative radiotherapy, and hormonal therapy to treat choroidal and orbital metastases is not known. Herein, we report the case of a 48-year-old woman with systemic chemotherapy-resistant choroidal and orbital metastases of the left eye originating from a stage IV invasive ductal carcinoma of the left breast. We describe the addition of a single intravitreal injection of bevacizumab in addition to treatment with systemic chemotherapy, hormonal therapy, and palliative radiotherapy. The patient's outcome at 6-month follow-up was favorable, as the metastatic lesion reduced in size and visual acuity improved. Combined treatment with intravitreal bevacizumab injection, systemic chemotherapy, palliative radiotherapy, and hormonal therapy can resolve ocular metastatic lesions originating from breast cancers.}, } @article {pmid33921735, year = {2021}, author = {Oprean, CM and Badau, LM and Segarceanu, NA and Ciocoiu, AD and Rivis, IA and Vornicu, VN and Hoinoiu, T and Grujic, D and Bredicean, C and Dema, A}, title = {Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {33921735}, issn = {2075-4418}, abstract = {The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.}, } @article {pmid33917306, year = {2021}, author = {Kothari, C and Clemenceau, A and Ouellette, G and Ennour-Idrissi, K and Michaud, A and Diorio, C and Durocher, F}, title = {Is Carboxypeptidase B1 a Prognostic Marker for Ductal Carcinoma In Situ?.}, journal = {Cancers}, volume = {13}, number = {7}, pages = {}, pmid = {33917306}, issn = {2072-6694}, abstract = {Ductal carcinoma in situ (DCIS) is considered a non-obligatory precursor for invasive ductal carcinoma (IDC). Around 70% of women with atypical ductal hyperplasia (ADH) undergo unnecessary surgery due to the difficulty in differentiating ADH from low-grade DCIS. If untreated, 14-60% of DCIS progress to IDC, highlighting the importance of identifying a DCIS gene signature. Human transcriptome data of breast tissue samples representing each step of BC progression were analyzed and high expression of carboxypeptidase B1 (CPB1) expression strongly correlated with DCIS. This was confirmed by quantitative PCR in breast tissue samples and cell lines model. High CPB1 expression correlated with better survival outcome, and mRNA level was highest in DCIS than DCIS adjacent to IDC and IDC. Moreover, loss of CPB1 in a DCIS cell line led to invasive properties associated with activation of HIF1α, FN1, STAT3 and SPP1 and downregulation of SFRP1 and OS9. The expression of CPB1 could predict 90.1% of DCIS in a cohort consisting of DCIS and IDC. We identified CPB1, a biomarker that helps differentiate DCIS from ADH or IDC and in predicting if a DCIS is likely to progress to IDC, thereby helping clinicians in their decisions.}, } @article {pmid33915261, year = {2021}, author = {López-Salazar, V and Tapia, MS and Tobón-Cornejo, S and Díaz, D and Alemán-Escondrillas, G and Granados-Portillo, O and Noriega, L and Tovar, AR and Torres, N}, title = {Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil.}, journal = {The Journal of nutritional biochemistry}, volume = {94}, number = {}, pages = {108751}, doi = {10.1016/j.jnutbio.2021.108751}, pmid = {33915261}, issn = {1873-4847}, mesh = {Animals ; Bacteria/classification/genetics ; Cells, Cultured ; Coconut Oil/*pharmacology ; Computational Biology ; DNA, Bacterial/genetics ; Feces/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Regulation/drug effects ; Genotype ; Glucose Intolerance ; Hepatocytes/drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/genetics/metabolism ; Non-alcoholic Fatty Liver Disease/*prevention & control ; Olive Oil/*pharmacology ; Oxygen Consumption/drug effects ; PPAR alpha/genetics/*metabolism ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S ; Random Allocation ; Soybean Oil/*pharmacology ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {Diets rich in mono or polyunsaturated fats have been associated with a healthy phenotype, but there is controversial evidence about coconut oil (CO), which is rich in saturated medium-chain fatty acids. Therefore, the purpose of the present work was to study whether different types of oils rich in polyunsaturated (soybean oil, SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO) can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial function in wild type and PPARα KO mice. The group that received SO showed the highest microbial diversity, increase in Akkermansia muciniphila, high insulin sensitivity and low grade inflammation, The OO group showed similar insulin sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in fatty acid oxidation and low grade inflammation. The CO consumption led to the lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-cholesterol concentration and the lowest respiratory capacity and fatty acid oxidation in the mitochondria. The absence of PPARα decreased alpha diversity and increased LPS concentration particularly in the CO group, and increased insulin sensitivity in the groups fed SO or OO. These results indicate that consuming mono or polyunsaturated fatty acids produced health benefits at the recommended intake but a high concentration of oils (three times the recommended oil intake in rodents) significantly decreased the microbial alpha-diversity independent of the type of oil.}, } @article {pmid33907159, year = {2021}, author = {He, Q and Xue, S and Wa, Q and He, M and Feng, S and Chen, Z and Chen, W and Luo, X}, title = {Mining immune-related genes with prognostic value in the tumor microenvironment of breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {100}, number = {17}, pages = {e25715}, pmid = {33907159}, issn = {1536-5964}, support = {No. 81572769, No. 81372238//National Natural Science Foundation of China/ ; 2016ZDXM006//Natural Science Foundation of Chongqing (CN)/ ; No. 20PJ198//Scientific Research Foundation of Health Commission of Sichuan Provinc/ ; }, mesh = {Biomarkers, Tumor/*genetics ; *Breast Neoplasms/genetics/immunology/pathology ; *Carcinoma, Ductal/genetics/immunology/pathology ; Databases, Genetic ; Female ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; Kaplan-Meier Estimate ; Molecular Targeted Therapy/methods ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; *Tumor Microenvironment/genetics/immunology ; }, abstract = {The tumor microenvironment (TME) plays an important role in the development of breast cancer. Due to limitations in experimental conditions, the molecular mechanism of TME in breast cancer has not yet been elucidated. With the development of bioinformatics, the study of TME has become convenient and reliable.Gene expression and clinical feature data were downloaded from The Cancer Genome Atlas database and the Molecular Taxonomy of Breast Cancer International Consortium database. Immune scores and stromal scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data algorithm. The interaction of genes was examined with protein-protein interaction and co-expression analysis. The function of genes was analyzed by gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and gene set enrichment analysis. The clinical significance of genes was assessed with Kaplan-Meier analysis and univariate/multivariate Cox regression analysis.Our results showed that the immune scores and stromal scores of breast invasive ductal carcinoma (IDC) were significantly lower than those of invasive lobular carcinoma. The immune scores were significantly related to overall survival of breast IDC patients and both the immune and stromal scores were significantly related to clinical features of these patients. According to the level of immune/stromal scores, 179 common differentially expressed genes and 5 hub genes with prognostic value were identified. In addition, the clinical significance of the hub genes was validated with data from the molecular taxonomy of breast cancer international consortium database, and gene set enrichment analysis analysis showed that these hub genes were mainly enriched in signaling pathways of the immune system and breast cancer.We identified five immune-related hub genes with prognostic value in the TME of breast IDC, which may partly determine the prognosis of breast cancer and provide some direction for development of targeted treatments in the future.}, } @article {pmid33907012, year = {2021}, author = {Rand, D and Cooper, I}, title = {Caspase-1: an important player and possible target for repair of the blood-brain barrier underlying neurodegeneration.}, journal = {Neural regeneration research}, volume = {16}, number = {12}, pages = {2390-2392}, pmid = {33907012}, issn = {1673-5374}, } @article {pmid33905446, year = {2021}, author = {Buchs, G and Haimler, B and Kerem, M and Maidenbaum, S and Braun, L and Amedi, A}, title = {A self-training program for sensory substitution devices.}, journal = {PloS one}, volume = {16}, number = {4}, pages = {e0250281}, pmid = {33905446}, issn = {1932-6203}, mesh = {Acoustic Stimulation/instrumentation/methods ; Adult ; *Algorithms ; Auditory Perception/physiology ; Biofeedback, Psychology ; Female ; Healthy Volunteers ; Humans ; Learning/*physiology ; Male ; *Sensory Aids ; Touch Perception/physiology ; Visually Impaired Persons/*rehabilitation ; *Wearable Electronic Devices ; }, abstract = {Sensory Substitution Devices (SSDs) convey visual information through audition or touch, targeting blind and visually impaired individuals. One bottleneck towards adopting SSDs in everyday life by blind users, is the constant dependency on sighted instructors throughout the learning process. Here, we present a proof-of-concept for the efficacy of an online self-training program developed for learning the basics of the EyeMusic visual-to-auditory SSD tested on sighted blindfolded participants. Additionally, aiming to identify the best training strategy to be later re-adapted for the blind, we compared multisensory vs. unisensory as well as perceptual vs. descriptive feedback approaches. To these aims, sighted participants performed identical SSD-stimuli identification tests before and after ~75 minutes of self-training on the EyeMusic algorithm. Participants were divided into five groups, differing by the feedback delivered during training: auditory-descriptive, audio-visual textual description, audio-visual perceptual simultaneous and interleaved, and a control group which had no training. At baseline, before any EyeMusic training, participants SSD objects' identification was significantly above chance, highlighting the algorithm's intuitiveness. Furthermore, self-training led to a significant improvement in accuracy between pre- and post-training tests in each of the four feedback groups versus control, though no significant difference emerged among those groups. Nonetheless, significant correlations between individual post-training success rates and various learning measures acquired during training, suggest a trend for an advantage of multisensory vs. unisensory feedback strategies, while no trend emerged for perceptual vs. descriptive strategies. The success at baseline strengthens the conclusion that cross-modal correspondences facilitate learning, given SSD algorithms are based on such correspondences. Additionally, and crucially, the results highlight the feasibility of self-training for the first stages of SSD learning, and suggest that for these initial stages, unisensory training, easily implemented also for blind and visually impaired individuals, may suffice. Together, these findings will potentially boost the use of SSDs for rehabilitation.}, } @article {pmid33898985, year = {2021}, author = {Schnitzler, C and Seifert, L and Button, C}, title = {Adaptability in Swimming Pattern: How Propulsive Action Is Modified as a Function of Speed and Skill.}, journal = {Frontiers in sports and active living}, volume = {3}, number = {}, pages = {618990}, pmid = {33898985}, issn = {2624-9367}, abstract = {The objectives of this study were to identify how spatiotemporal, kinetic, and kinematic parameters could (i) characterize swimmers' adaptability to different swimming speeds and (ii) discriminate expertise level among swimmers. Twenty male participants, grouped into (a) low-, (b) medium-, and (c) high-expertise levels, swam at four different swim paces of 70, 80, 90% (for 20 s), and 100% (for 10 s) of their maximal speed in a swimming flume. We hypothesized that (i) to swim faster, swimmers increase both propulsion time and the overall force impulse during a swimming cycle; (ii) in the frequency domain, expert swimmers are able to maintain the relative contribution of the main harmonics to the overall force spectrum. We used three underwater video cameras to derive stroking parameters [stroke rate (SR), stroke length (SL), stroke index (SI)]. Force sensors placed on the hands were used to compute kinetic parameters, in conjunction with video data. Parametric statistics examined speed and expertise effects. Results showed that swimmers shared similarities across expertise levels to increase swim speed: SR, the percentage of time devoted to propulsion within a cycle, and the index of coordination (IdC) increased significantly. In contrast, the force impulse (I [+]) generated by the hand during propulsion remained constant. Only the high-expertise group showed modification in the spectral content of its force distribution at high SR. Examination of stroking parameters showed that only high-expertise swimmers exhibited higher values of both SL and SI and that the low- and high-expertise groups exhibited similar IdC and even higher magnitude in I [+]. In conclusion, all swimmers exhibit adaptable behavior to change swim pace when required. However, high-skilled swimming is characterized by broader functional adaptation in force parameters.}, } @article {pmid33898857, year = {2021}, author = {Mahalingam, S and Peter, J and Xu, Z and Bordoloi, D and Ho, M and Kalyanaraman, VS and Srinivasan, A and Muthumani, K}, title = {Landscape of humoral immune responses against SARS-CoV-2 in patients with COVID-19 disease and the value of antibody testing.}, journal = {Heliyon}, volume = {7}, number = {4}, pages = {e06836}, pmid = {33898857}, issn = {2405-8440}, abstract = {A new pandemic is ongoing in several parts of the world. The agent responsible is the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The symptoms associated with this virus are known as the coronavirus disease-2019 (COVID-19). In this review, we summarize the published data on virus specific antibodies in hospitalized patients with COVID-19 disease, patients recovered from the disease and the individuals who are asymptomatic with SARS-CoV-2 infections. The review highlights the following: i) an adjunct role of antibody tests in the diagnosis of COVID-19 in combination with RT-PCR; ii) status of antibodies from COVID-19 convalescent patients to select donors for plasma therapy; iii) the potential confounding effects of other coronaviruses, measles, mumps and rubella in antibody testing due to homology of certain viral genes; and iv) the role of antibody testing for conducting surveillance in populations, incidence estimation, contact tracing and epidemiologic studies.}, } @article {pmid33898059, year = {2021}, author = {Al Abri, S and Al Rawahi, A and Rao, L}, title = {Elastosis in Breast Cancer as a Surrogate Marker for Estrogen Receptor Positivity.}, journal = {Oman medical journal}, volume = {36}, number = {2}, pages = {e247}, pmid = {33898059}, issn = {1999-768X}, abstract = {OBJECTIVES: We sought to describe the occurrence of stromal elastosis in breast carcinoma among Omani female patients using semi-quantitative methods. We also sought to investigate the relationship between stromal elastosis and estrogen receptor (ER), progesterone receptor (PR), HER2/neu receptor tumor grade, and Ki-67 index. Furthermore, we evaluated the diagnostic accuracy of hematoxylin and eosin (H&E) stain method in quantifying elastosis compared to Elastin van Gieson (EVG) stain and if elastosis can be used as prognostic marker for overall survival.

METHODS: The content of elastic tissue in primary infiltrating carcinomas of the breast was assessed using semi-quantitative methods (H&E and EVG stains) in 80 female Omani patients by two independent pathologists. Data of primary breast cancer patients who were not treated with neoadjuvant therapy from 2009 to 2019 at the Armed Forces Hospital of Oman were collected from medical records. Demographic and clinical data, including age, menstrual status, tumor type and grade, ER, PR, HER2/neu status, and Ki-67 index were obtained. Follow-up data, including clinical remission, evidence of metastasis, death, or lost follow-up were traced from medical records.

RESULTS: Among the 80 cases studied, 80.0% were diagnosed with invasive ductal carcinoma, not otherwise specified, while 12.6% were diagnosed with infiltrating lobular carcinoma. Interobserver agreement of grading elastosis on H&E and EVG was strong (Kappa coefficient = 0.858). Using EVG, absent elastosis, grade 1, grade 2, and grade 3 were observed in 12.5%, 37.5%, 30.0%, and 20.0%, respectively. A statistically significant relationship between high elastosis and ER positivity (p = 0.015) and negative HER2/neu receptor (p = 0.045) was observed. No statistically significant relationship between elastosis and other entities, including menopausal status, tumor type and grade, PR, Ki-67, and prognosis. The sensitivity and specificity of quantifying elastosis on H&E stained sections compared to EVG stain (the gold standard) were 68.75% and 96.88%, respectively.

CONCLUSIONS: Elastosis occurrence varies in different breast cancer populations. Elastosis can be considered a surrogate marker for estrogen positivity and HER2/neu negativity in breast cancer patients. In addition, H&E stain is considered an accurate method for quantifying elastosis compared to the EVG staining method.}, } @article {pmid33895652, year = {2021}, author = {Heimler, B and Behor, T and Dehaene, S and Izard, V and Amedi, A}, title = {Core knowledge of geometry can develop independently of visual experience.}, journal = {Cognition}, volume = {212}, number = {}, pages = {104716}, doi = {10.1016/j.cognition.2021.104716}, pmid = {33895652}, issn = {1873-7838}, mesh = {Adult ; Blindness ; Child ; Humans ; Knowledge ; Mathematics ; Touch ; *Touch Perception ; Vision, Ocular ; }, abstract = {Geometrical intuitions spontaneously drive visuo-spatial reasoning in human adults, children and animals. Is their emergence intrinsically linked to visual experience, or does it reflect a core property of cognition shared across sensory modalities? To address this question, we tested the sensitivity of blind-from-birth adults to geometrical-invariants using a haptic deviant-figure detection task. Blind participants spontaneously used many geometric concepts such as parallelism, right angles and geometrical shapes to detect intruders in haptic displays, but experienced difficulties with symmetry and complex spatial transformations. Across items, their performance was highly correlated with that of sighted adults performing the same task in touch (blindfolded) and in vision, as well as with the performances of uneducated preschoolers and Amazonian adults. Our results support the existence of an amodal core-system of geometry that arises independently of visual experience. However, performance at selecting geometric intruders was generally higher in the visual compared to the haptic modality, suggesting that sensory-specific spatial experience may play a role in refining the properties of this core-system of geometry.}, } @article {pmid33893728, year = {2021}, author = {Song, Y and Sun, H and Wu, K and Lyu, J and Zhang, J and Gu, F and Ma, Y and Shen, B and Wang, C and Chen, X and Xu, J and Li, W and Liu, F and Fu, L}, title = {sLe[x] expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator.}, journal = {Cancer biology & medicine}, volume = {18}, number = {2}, pages = {477-489}, pmid = {33893728}, issn = {2095-3941}, support = {81672637//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: Mucin 1 (MUC1/EMA) and sialyl Lewis X (sLe[x]) indicate polarity reversal in invasive micropapillary carcinoma (IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLe[x] and to assess their diagnostic and prognostic value in patients with IMPC.

METHODS: The expression of sLe[x] and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis.

RESULTS: The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLe[x] and MUC1/EMA in the cytomembranes (the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLe[x], but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLe[x]+/EMA- expression patterns, and 8 patients had sLe[x]-/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLex were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells.

CONCLUSIONS: sLe[x] can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.}, } @article {pmid33890520, year = {2022}, author = {van Lierop, ZY and Wieske, L and Koel-Simmelink, MJ and Chatterjee, M and Dekker, I and Leurs, CE and Willemse, EA and Moraal, B and Barkhof, F and Eftimov, F and Uitdehaag, BM and Killestein, J and Teunissen, CE}, title = {Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {28}, number = {1}, pages = {102-110}, pmid = {33890520}, issn = {1477-0970}, mesh = {Biomarkers ; Contactin 1 ; Disease Progression ; Humans ; Immunologic Factors ; *Multiple Sclerosis ; *Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Natalizumab ; }, abstract = {BACKGROUND: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS).

OBJECTIVE: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients.

METHODS: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria.

RESULTS: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04-1.45) (p = 0.017) for progression during follow-up.

CONCLUSION: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS.}, } @article {pmid33889201, year = {2021}, author = {Ali-Gombe, M and Mustapha, MI and Folasire, A and Ntekim, A and Campbell, OB}, title = {Pattern of survival of breast cancer patients in a tertiary hospital in South West Nigeria.}, journal = {Ecancermedicalscience}, volume = {15}, number = {}, pages = {1192}, pmid = {33889201}, issn = {1754-6605}, abstract = {BACKGROUND OF THE STUDY: Breast cancer is the most common cancer among women in both developed and developing nations. The survival of breast cancer is increasing in developed countries with improved treatment modalities, while still very poor in developing countries. In Nigeria, few breast cancer survival data are available.

RESEARCH DESIGN: This is a retrospective cross-sectional study.

OBJECTIVES: To determine the survival of breast cancer patients and possible factors influencing it.

METHODOLOGY: Socio-demographic and clinical variables from treatment records and case notes of breast cancer patients treated from 1 January 2004 to 31 December 2008 at the Department of Radiation Oncology, University College Hospital, Ibadan. The status of patients was determined at 2 and 5 years after diagnosis. The survival of patients with breast cancer was compared using Log Rank test according to socio-demographic and clinical variables. The median survival times were obtained from the Kaplan-Meier survival curve. Cox's proportional hazard model was fitted for those that were statistically significant in the Log Rank test. Missing data were reported as unknown, not documented or missing.

RESULTS: A total of 378 patients were analysed. Age ranged between 22.0 and 87.0 years with mean of 47.6 (standard deviation (SD) = 11.2) years. Almost all patients were females (98.4%). More than half (55.3%) presented at stage III, 28.0% had metastasis and the stage was unknown in about 6.6% of the patients. Invasive ductal carcinoma was the most prevalent histology (89.2%). Only 124 (32.8%) patients had their histological grade stated and most of the patients had no immunohistochemistry done. All the patients had radiotherapy, chemotherapy and surgery. About 25.1% of the patients were lost to follow up. The 2- and 5-year survival rates were 56.4% and 37.6%, respectively. The 2- and 5-year survival rates according to stage were stage I (80.0% and 66.7%), stage II (67.7% and 57.6%), stage III (51.4% and 27.9%) and stage IV (37.9% and 13.8%). Median survival time was 41 months (95%CI = 35.0-44.0). The disease-free survival at 2 and 5 years was 66.6% and 60.3%, respectively. Median time for recurrence was 8.0 months. Level of education, height, tumour unilaterality, clinical tumour size, stage at presentation, presence of distant metastases, clinical axillary lymph node metastasis, supraclavicular node metastasis, mode of surgery and axillary clearance were found to have statistically significant association with survival.

CONCLUSION: A large number of the patients in our study presented at a young age, late with advanced stage disease which results in poor survival outcome.}, } @article {pmid33888841, year = {2021}, author = {Fang, WB and Sofia Acevedo, D and Smart, C and Zinda, B and Alissa, N and Warren, K and Fraga, G and Huang, LC and Shyr, Y and Li, W and Xie, L and Staggs, V and Hong, Y and Behbod, F and Cheng, N}, title = {Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8708}, pmid = {33888841}, issn = {2045-2322}, support = {P20 GM130423/GM/NIGMS NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; R01 CA207445/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Chemokine CCL2/*metabolism ; Disease Progression ; Female ; Heterografts ; Humans ; Mice ; Middle Aged ; *Neoplasm Invasiveness ; Receptors, CCR2/*metabolism ; *Signal Transduction ; }, abstract = {Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.}, } @article {pmid33888263, year = {2021}, author = {Schaub, JR and Tang, SC}, title = {Delayed Gemcitabine-Induced Posterior Reversible Encephalopathy Syndrome.}, journal = {The American journal of the medical sciences}, volume = {361}, number = {6}, pages = {795-798}, doi = {10.1016/j.amjms.2020.10.030}, pmid = {33888263}, issn = {1538-2990}, mesh = {Antimetabolites, Antineoplastic/*adverse effects ; Deoxycytidine/adverse effects/*analogs & derivatives ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Posterior Leukoencephalopathy Syndrome/*chemically induced/*diagnostic imaging ; Time Factors ; Gemcitabine ; }, abstract = {INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiographic syndrome that has been expanding rapidly in the world of clinical medical oncology and hematology. In this article, we provide a unique patient case of delayed gemcitabine-induced PRES.

BRIEF CASE REPORT: A 60-year-old African American female with significant past medical history of ER+/PR+/HER2- invasive ductal carcinoma of the left breast is seen in the medical oncology clinic with vague, mild complaints of lightheadedness. She had progressed on multiple lines of chemotherapy and was ultimately switched to gemcitabine. One month after her third dose of gemcitabine, she developed acute vision loss and soon developed generalized tonic-clonic seizure. Extensive workup was unrevealing other than PRES and she slowly improved with supportive care and withdrawal of the medication.

DISCUSSION: Multiple case reports have described PRES in the context of combination chemotherapy with gemcitabine and a platinum agent in the treatment of gastrointestinal malignancies. With growing evidence, this case is consistent with the hypothesis that gemcitabine as monotherapy has a direct association with PRES. This case highlights a unique aspect in that PRES can occur at a delayed time interval, much further than the expected hours to days after the previous treatment.}, } @article {pmid33884501, year = {2022}, author = {Chudal, R and Tiiri, E and Brunstein Klomek, A and Ong, SH and Fossum, S and Kaneko, H and Kolaitis, G and Lesinskiene, S and Li, L and Huong, MN and Praharaj, SK and Sillanmäki, L and Slobodskaya, HR and Srabstein, JC and Wiguna, T and Zamani, Z and Sourander, A and , }, title = {Victimization by traditional bullying and cyberbullying and the combination of these among adolescents in 13 European and Asian countries.}, journal = {European child & adolescent psychiatry}, volume = {31}, number = {9}, pages = {1391-1404}, pmid = {33884501}, issn = {1435-165X}, support = {320162//Academy of Finland/ ; 308552//Academy of Finland/ ; 16-18-00003//Russian Scientific Foundation/ ; }, mesh = {Adolescent ; *Bullying/psychology ; *Crime Victims/psychology ; Cross-Sectional Studies ; *Cyberbullying/psychology ; Female ; Humans ; Male ; Schools ; }, abstract = {There has been a lack of studies on bullying in non-western low-income and middle-income countries. This study reported the prevalence of traditional victimization, cybervictimization, and the combination of these, in 13 European and Asian countries, and explored how psychiatric symptoms were associated with victimization. The data for this cross-sectional, school-based study of 21,688 adolescents aged 13-15 were collected from 2011 to 2017. The main outcomes were traditional and cybervictimization obtained from student self-reports. The Strengths and Difficulties Questionnaire was used to assess psychiatric symptoms. Generalized estimating equation and logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). The mean prevalence of any victimization was 28.9%, of traditional victimization only, this was 17.7%, and for cybervictimization only this was 5.1%. Cybervictimization occurred both independently, and in combination with, traditional victimization. The mean prevalence of combined victimization was 6.1%. The mean proportion of those who were cyberbullied only among those who were either cyberbullied only or bullied both traditionally and in cyber was 45.1%. The rates of prevalence varied widely between countries. In the total sample, those who experienced combined victimization, reported the highest internalizing symptoms (girls, OR 1.25, 95% CI 1.22-1.29; boys, OR 1.29, 95% CI 1.25-1.33). The study findings suggest that anti-bullying interventions should include mental health components and target both traditional and cyberbullying. Due to the overlap between these, targeting bullying should primarily focus on how to reduce bullying behavior rather than just focusing on where bullying takes place.}, } @article {pmid33881947, year = {2021}, author = {Zhang, C and Wang, EY and Liu, F and Ruhul Quddus, M and James Sung, C}, title = {Type of Architecture, Presence of Punctate Necrosis, and Extent of Involvement in Atypical Ductal Hyperplasia Can Predict the Diagnosis of Breast Carcinoma on Excision: A Clinicopathologic Study of 143 Cases.}, journal = {International journal of surgical pathology}, volume = {29}, number = {7}, pages = {716-721}, doi = {10.1177/10668969211010954}, pmid = {33881947}, issn = {1940-2465}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/statistics & numerical data ; Breast Neoplasms/*diagnosis/epidemiology/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/epidemiology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology/surgery ; Female ; Humans ; Hyperplasia/diagnosis/pathology/surgery ; Mammary Glands, Human/*pathology/surgery ; Mastectomy, Segmental/*statistics & numerical data ; Middle Aged ; Necrosis/diagnosis/pathology/surgery ; Prognosis ; Reproducibility of Results ; Risk Assessment/methods/statistics & numerical data ; }, abstract = {The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was <2 mm and type B was considered when one or more ducts were partially involved by low-grade ductal carcinoma in situ type cells regardless of lesion size. Type A was associated with a significantly higher frequency of breast carcinoma (63.6%) than type B (30.0%). ADH containing punctate necrosis showed a higher association of carcinoma (66.7%) compared to those without necrosis (35.1%). Within type B ADH, involvement of 3 or more foci had a higher frequency of carcinoma (50.0%) than involvement of fewer foci (26.6%). These histologic features of ADH may prove useful in predicting the likelihood of breast carcinoma and provide helpful information for patient's management.}, } @article {pmid33868044, year = {2021}, author = {Blum, K and Khalsa, J and Cadet, JL and Baron, D and Bowirrat, A and Boyett, B and Lott, L and Brewer, R and Gondré-Lewis, M and Bunt, G and Kazmi, S and Gold, MS}, title = {Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {623403}, pmid = {33868044}, issn = {1664-0640}, support = {U54 MD007597/MD/NIMHD NIH HHS/United States ; }, abstract = {Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce 'dopamine homeostasis,' that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.}, } @article {pmid33863935, year = {2021}, author = {Nobili, S and Mannini, A and Parenti, A and Raggi, C and Lapucci, A and Chiorino, G and Paccosi, S and Di Gennaro, P and Vezzosi, V and Romagnoli, P and Susini, T and Coronnello, M}, title = {Establishment and characterization of a new spontaneously immortalized ER[-]/PR[-]/HER2[+] human breast cancer cell line, DHSF-BR16.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8340}, pmid = {33863935}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/drug therapy/*genetics/*pathology/surgery ; CD24 Antigen/genetics/metabolism ; Carcinoma, Ductal/drug therapy/*genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Movement ; Chemotherapy, Adjuvant ; Epithelial Cell Adhesion Molecule/genetics/metabolism ; Female ; Humans ; Hyaluronan Receptors/genetics/metabolism ; Intracellular Membranes/metabolism ; Keratin-7/genetics/metabolism ; Keratin-8/genetics/metabolism ; Neoadjuvant Therapy ; *Receptor, ErbB-2 ; *Receptors, Estrogen ; *Receptors, Progesterone ; Spheroids, Cellular/pathology ; }, abstract = {Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER[-]/PR[-]/HER2[+], and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44[+]/CD24[-/low]), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.}, } @article {pmid33863696, year = {2021}, author = {Rebollo Aguirre, AC and Fernández Fernández, J and Sánchez Sánchez, R and Mendoza Arnau, I and Rivas Navas, DJ and Martínez Meca, S}, title = {Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.remn.2021.02.017}, pmid = {33863696}, issn = {2253-8089}, abstract = {OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC).

MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%.

RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm[3]. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients.

CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.}, } @article {pmid33863525, year = {2021}, author = {D'Iorio, A and Esposito, M and Maggi, G and Amboni, M and Vitale, C and Santangelo, G}, title = {Neuropsychological correlates of prospective memory: A comparison between tremor-dominant Parkinson's disease and cervical dystonia.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {87}, number = {}, pages = {156-161}, doi = {10.1016/j.jocn.2021.03.006}, pmid = {33863525}, issn = {1532-2653}, mesh = {Aged ; Cognitive Dysfunction/diagnosis/etiology/*psychology ; Executive Function/physiology ; Female ; Humans ; Male ; Memory Disorders/diagnosis/etiology/psychology ; *Memory, Episodic ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/complications/diagnosis/*psychology ; Retrospective Studies ; Torticollis/complications/diagnosis/*psychology ; Tremor/complications/diagnosis/*psychology ; }, abstract = {Cervical Dystonia (CD) and Parkinson's disease, particularly tremor-dominant motor phenotype (TD-PD), showed a selective deficit of time-based prospective memory (TBPM). The two movement disorders are mainly characterized by dysfunctions of basal-ganglia and prefrontal cortex but it is reported that cerebellum also plays a key role in their pathogenesis. These cerebral structures are specifically involved in TBPM rather than in event-based PM (EBPM), but until now no study directly compared these two components of PM between CD and TD-PD patients. Therefore, the present study aimed at investigating if differences in PM functioning between CD and TD-PD patients might exist and if the type of movement disorder moderated the relationship between deficit of PM and deficit of executive functions and retrospective memory. Thirty TD-PD, 27CD patients and 29 healthy subjects (HCs), matched for demographic features, underwent neuropsychological tests for PM, executive functions, retrospective memory and self-rated questionnaires. The three groups did not differ on neuropsychological variables except for TBPM where TD-PD and CD patients performed worse than HCs; moreover, TD-PD performed worse than CD patients. Moderation analysis indicated that the type of movement disorder moderated the relationship between executive dysfunction and TBPM, but not EBPM. In conclusion, selective deficit of TBPM characterizes both CD and TD-PD but it is associated with executive dysfunction only in TD-PD. It might be possible to speculate that the involvement of the cerebellum, responsible for internal timing processes, could explain the impairment of TBPM in both movement disorders. This issue deserves to be explored in future neuroimaging studies.}, } @article {pmid33859904, year = {2021}, author = {Alaref, A and Hassan, A and Sharma Kandel, R and Mishra, R and Gautam, J and Jahan, N}, title = {Magnetic Resonance Imaging Features in Different Types of Invasive Breast Cancer: A Systematic Review of the Literature.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e13854}, pmid = {33859904}, issn = {2168-8184}, abstract = {Breast cancer is the most common malignancy affecting women worldwide, and early diagnosis of breast cancer is the key to its successful and effective treatment. Traditional imaging techniques such as mammography and ultrasound are used to detect and configure breast abnormalities; unfortunately, these modalities have low sensitivity and specificity, particularly in young patients with dense breast tissue, breast implants, or post-surgical scar/architecture distortions. Therefore, breast magnetic resonance imaging (MRI) has been superior in the characterization and detection of breast cancer, especially that with invasive features. This review article explores the importance of breast MRI in the early detection of invasive breast cancer versus traditional tools, including mammography and ultrasound, while also analyzing the use of MRI as a screening tool for high-risk women. We will also discuss the different MRI features for invasive ductal carcinoma and lobular carcinoma and the role of breast MRI in the detection of ductal carcinoma in situ with a focus on the utilization of new techniques, including MR spectroscopy and diffusion-weighted imaging.}, } @article {pmid33857828, year = {2021}, author = {Li, Q and Xiao, Q and Yang, M and Chai, Q and Huang, Y and Wu, PY and Niu, Q and Gu, Y}, title = {Histogram analysis of quantitative parameters from synthetic MRI: Correlations with prognostic factors and molecular subtypes in invasive ductal breast cancer.}, journal = {European journal of radiology}, volume = {139}, number = {}, pages = {109697}, doi = {10.1016/j.ejrad.2021.109697}, pmid = {33857828}, issn = {1872-7727}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: To evaluate intra-tumoral heterogeneity through a histogram analysis of quantitative parameters obtained from synthetic MRI (magnetic resonance imaging), and determine correlations of these histogram characteristics with prognostic factors and molecular subtypes of invasive ductal carcinoma (IDC).

METHODS: A total of 122 IDC from 122 women who underwent preoperative synthetic MRI and DCE (dynamic contrast enhancement)-MRI were investigated. The synthetic MRI parameters (T1, T2, and PD (proton density)) were obtained. For each parameter, the minimum, 10th percentile, mean, median, 90th percentile, maximum, skewness, and kurtosis values of tumor were calculated, and correlations with prognostic factors and subtypes were assessed. The Mann-Whitney U test or the Student[']s t test were utilized to analyze the association between the histogram features of synthetic MRI parameters and prognostic factors. The Kruskal-Wallis test followed by the post-hoc test was used to analyze differences of synthetic MRI parameters among molecular subtypes.

RESULTS: IDC with high histopathologic grade showed statistically higher PDmaxium, T1mean and T1median values than those with low grade (p = 0.003, p = 0.007, p = 0.003). The T110th were significantly higher in cancers with PR (progesterone receptor) negativity than those with PR positivity (p = 0.005). ER-negative cancers had significant higher values of T210th, T2mean, and T2median than ER-positive cancers (p = 0.006, 0.002, and 0.006, respectively). The values of PDmedian were significantly higher in IDC with HER2 (human epidermal growth factor receptor 2) positivity than those with HER2 negativity (p = 0.001). When discriminating molecular subtypes of IDC, the T2mean achieved the highest performance. The T2mean values of TN (triple-negative), luminal B and luminal A types are arranged in descending order (p <  0.0001).

CONCLUSIONS: Histogram features derived from synthetic MRI quantifies the distributions of tissue relaxation time and proton density, and may serve as a potential biomarker for discriminating histopathological grade, hormone receptor status, HER2 expression status and breast cancer subtypes.}, } @article {pmid33855763, year = {2021}, author = {Powell, M and Gate, T and Kalake, O and Ranjith, C and Pennick, MO}, title = {Magnetic Seed Localization (Magseed) for excision of impalpable breast lesions-The North Wales experience.}, journal = {The breast journal}, volume = {27}, number = {6}, pages = {529-536}, doi = {10.1111/tbj.14232}, pmid = {33855763}, issn = {1524-4741}, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; Female ; Humans ; Magnetic Phenomena ; Margins of Excision ; Mastectomy, Segmental ; Wales ; }, abstract = {The breast surgical community has faced huge challenges due to close working relationships with radiologists who are in short supply. Breast lesion localization is moving away from the traditional wire technique, which requires an on-site radiologist to support theater scheduling. In North Wales, the introduction of Magseed for impalpable breast lesion localization has facilitated theater scheduling in the absence of same day radiology presence. We audited our first 200 Magseed cases to assess the safety and efficacy of the technique, the ease of use, and patient experience. Data were entered prospectively into an excel data base relating to Magseed cases. Data collected included demographics, pre and postoperative lesion size, histology, margin positivity, and re-excision rates. Data were submitted in real time by the radiologist performing Magseed insertion to ascertain degree of difficulty. A PROMS questionnaire was designed and sent to patients undergoing Magseed vs wire localizations. Two hundred patients underwent Magseed-guided wide local excision between May 2018 and January 2020 across 2 district general hospital sites in North Wales. Histology: 69% IDC, 20% ILC, and 11% others. Mean preoperative size 12.3 mm, postoperative size 19 mm. Re-excision rate 15%. Re-excision for DCIS was significantly more likely than for invasive disease (p < 0.0001). A significant difference was also observed between radiological mean preoperative tumor size estimate and actual histological tumor size in patients undergoing margin re-excision (p = 0.000019). Wire-guided re-excision rate was 21% in the same unit. PROMs found the procedure well tolerated by patients. Surgeons and radiologists reported Magseed to be user-friendly with minimal learning curve. Magseed use for impalpable breast lesion localization is safe, user friendly, and well tolerated by patients. It produces favorable re-excision rates when compared to published figures for wire-guided excision. The presence of DCIS and preoperative radiological size underestimation was associated with margin re-excision.}, } @article {pmid33850600, year = {2021}, author = {Thompson, HK and Spicer, PJ}, title = {Recurrent breast cancer diagnosis delayed by COVID-19 pandemic.}, journal = {Radiology case reports}, volume = {16}, number = {6}, pages = {1489-1492}, pmid = {33850600}, issn = {1930-0433}, abstract = {We describe the case of a 65-year-old female with a history of left-sided ductal carcinoma in situ in 2008. Mammography in January 2020 demonstrated calcifications in the previously affected breast. Subsequent stereotactic biopsy results were benign. In the months that followed, the patient experienced breast changes but avoided returning to the facility as the COVID-19 pandemic worsened. In August of 2020, the patient returned for a repeat mammogram, which indicated 2 suspicious masses in the left breast. Further analysis through ultrasound-guided core biopsy ultimately led to a left mastectomy and lymph node biopsy, which were performed in September 2020. Pathology results revealed multifocal invasive ductal carcinoma stage IIB.}, } @article {pmid33850160, year = {2021}, author = {Fayad, R and Rojas, MV and Partisani, M and Finetti, P and Dib, S and Abelanet, S and Virolle, V and Farina, A and Cabaud, O and Lopez, M and Birnbaum, D and Bertucci, F and Franco, M and Luton, F}, title = {EFA6B regulates a stop signal for collective invasion in breast cancer.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2198}, pmid = {33850160}, issn = {2041-1723}, mesh = {Animals ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockout Techniques ; Guanine Nucleotide Exchange Factors/*genetics/*metabolism ; Humans ; Mice ; Mice, Nude ; Transcriptome ; cdc42 GTP-Binding Protein ; }, abstract = {Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.}, } @article {pmid33840267, year = {2021}, author = {Davidson, JL and Bergenstal, RM and Conry, JA and Taswell, R and Carlson, AL}, title = {Initiating Insulin in the Emergency Center and Urgent Care to Prevent Hospital Admission for Patients with Hyperglycemia: A Unique Insulin Starter Kit.}, journal = {Journal of diabetes science and technology}, volume = {15}, number = {4}, pages = {755-761}, pmid = {33840267}, issn = {1932-2968}, mesh = {Ambulatory Care ; Blood Glucose ; Blood Glucose Self-Monitoring ; *Diabetes Mellitus, Type 2 ; Hospitalization ; Hospitals ; Humans ; *Hyperglycemia/drug therapy/prevention & control ; Hypoglycemic Agents ; Insulin ; }, abstract = {BACKGROUND: Clinicians in the Emergency Center (EC) and Urgent Care (UC) can play a vital role in preventing hospital admissions and improving outcomes of patients with newly diagnosed diabetes or pre-existing diabetes who present with hyperglycemia and the need to initiate insulin.

METHODS: This article describes a unique EC/UC discharge insulin starter kit protocol with clinician instructions via an Electronic Medical Record (EMR) order set that includes: starting doses for insulin, a prescription for glucose monitoring supplies, and an emergent referral to diabetes education at International Diabetes Center. Patients receive insulin during the EC/UC visit and are provided an insulin pen to take home. Nurses from the EC or UC review and provide educational material on how to use an insulin pen, treating hypoglycemia and healthy eating. The Certified Diabetes Care and Education Specialist (CDCES) sees patients within 24-72 hours after the referral is placed.

RESULTS: Within our single healthcare system's EC and UC (multiple sites), the kit has enabled clinicians to metabolically stabilize patients and decrease the need for hospitalization without experiencing hypoglycemia. In the recent three years of use, of 42 patients given the insulin starter kit, there were only 2 patients with repeat EC/UC visits within the first six months (1 hyperglycemia and 1 hypoglycemia).

CONCLUSIONS: An insulin starter kit and EMR-based order set initiated in the EC/UC setting is a tool that can be used to improve the quality of care for people with newly diagnosed or pre-existing diabetes experiencing significant hyperglycemia.}, } @article {pmid33836269, year = {2021}, author = {Hofstetter, S and Zuiderbaan, W and Heimler, B and Dumoulin, SO and Amedi, A}, title = {Topographic maps and neural tuning for sensory substitution dimensions learned in adulthood in a congenital blind subject.}, journal = {NeuroImage}, volume = {235}, number = {}, pages = {118029}, doi = {10.1016/j.neuroimage.2021.118029}, pmid = {33836269}, issn = {1095-9572}, mesh = {Auditory Perception/*physiology ; Blindness/*physiopathology ; Brain/*physiology ; Humans ; Learning/*physiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; *Orientation ; }, abstract = {Topographic maps, a key principle of brain organization, emerge during development. It remains unclear, however, whether topographic maps can represent a new sensory experience learned in adulthood. MaMe, a congenitally blind individual, has been extensively trained in adulthood for perception of a 2D auditory-space (soundscape) where the y- and x-axes are represented by pitch and time, respectively. Using population receptive field mapping we found neural populations tuned topographically to pitch, not only in the auditory cortices but also in the parietal and occipito-temporal cortices. Topographic neural tuning to time was revealed in the parietal and occipito-temporal cortices. Some of these maps were found to represent both axes concurrently, enabling MaMe to represent unique locations in the soundscape space. This case study provides proof of concept for the existence of topographic maps tuned to the newly learned soundscape dimensions. These results suggest that topographic maps can be adapted or recycled in adulthood to represent novel sensory experiences.}, } @article {pmid33835493, year = {2021}, author = {Nash, Y and Ganoth, A and Borenstein-Auerbach, N and Levy-Barazany, H and Goldsmith, G and Kopelevich, A and Pozyuchenko, K and Sakhneny, L and Lazdon, E and Blanga-Kanfi, S and Alhadeff, R and Benromano, T and Landsman, L and Tsfadia, Y and Frenkel, D}, title = {From virus to diabetes therapy: Characterization of a specific insulin-degrading enzyme inhibitor for diabetes treatment.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {5}, pages = {e21374}, doi = {10.1096/fj.201901945R}, pmid = {33835493}, issn = {1530-6860}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Diabetes Mellitus, Experimental/etiology/pathology/*therapy ; Diabetes Mellitus, Type 1/etiology/pathology/*therapy ; Diabetes Mellitus, Type 2/etiology/pathology/*therapy ; Enzyme Inhibitors/administration & dosage ; Female ; Herpesvirus 3, Human/physiology ; Insulin/*metabolism ; Insulysin/*antagonists & inhibitors/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Peptide Fragments/*administration & dosage ; Viral Envelope Proteins/*metabolism ; }, abstract = {Inhibition of insulin-degrading enzyme (IDE) is a possible target for treating diabetes. However, it has not yet evolved into a medical intervention, mainly because most developed inhibitors target the zinc in IDE's catalytic site, potentially causing toxicity to other essential metalloproteases. Since IDE is a cellular receptor for the varicella-zoster virus (VZV), we constructed a VZV-based inhibitor. We computationally characterized its interaction site with IDE showing that the peptide specifically binds inside IDE's central cavity, however, not in close proximity to the zinc ion. We confirmed the peptide's effective inhibition on IDE activity in vitro and showed its efficacy in ameliorating insulin-related defects in types 1 and 2 diabetes mouse models. In addition, we suggest that inhibition of IDE may ameliorate the pro-inflammatory profile of CD4[+] T-cells toward insulin. Together, we propose a potential role of a designed VZV-derived peptide to serve as a selectively-targeted and as an efficient diabetes therapy.}, } @article {pmid33832078, year = {2021}, author = {Jung, SU and Jung, M and Choi, JH and Jeon, CW}, title = {Palbociclib with letrozole as second-line neo-systemic therapy after failure of neo-adjuvant chemotherapy for luminal type breast cancer: A case report.}, journal = {Medicine}, volume = {100}, number = {14}, pages = {e25175}, pmid = {33832078}, issn = {1536-5964}, mesh = {Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant/methods ; Female ; Humans ; Letrozole/*administration & dosage ; Lymphatic Metastasis/pathology ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy/adverse effects ; Piperazines/*administration & dosage ; Protein Kinase Inhibitors/*administration & dosage ; Pyridines/*administration & dosage ; }, abstract = {RATIONALE: Neo-adjuvant systemic therapy includes endocrine therapy and chemotherapy, which is widely used. Luminal breast cancer is resistant to chemotherapy and is more likely to not respond to chemotherapy before surgery. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor. Palbociclib with letrozole combination therapy was an effective chemotherapy in metastatic luminal type breast cancer and had fewer side effects; however, the benefit of palbociclib in neoadjuvant systemic therapy is unclear.

PATIENT CONCERNS: A 50-year-old female patient visited our hospital with palpable lump in the right breast. The lymph nodes fixed in the ipsilateral axilla.

DIAGNOSIS: The patient was diagnosed with invasive ductal carcinoma of the right breast; the nuclear grade was moderate. The ipsilateral fixed lymph node was diagnosed as metastasis. The breast cancer subtype was luminal A type and was positive for estrogen receptor and progesterone receptor, and negative for HER2/neu and Ki-67 marker index <10% on immunohistochemistry.

INTERVENTIONS: Neo-systemic therapy was performed with 3 cycles of adriamycin with docetaxel. After follow-up study, the breast and axillary lesions progressed. Palbociclib with letrozole was administered as second neo-systemic therapy for 10 months. Subsequently, breast-conserving surgery with sentinel lymph node biopsy was performed.

OUTCOMES: In the postoperative pathologic result, 4 mm invasive lesion remained, and the sentinel lymph node biopsy was negative. The results achieved a residual cancer burden classification class 1.

CONCLUSION: Second-line neo-systemic therapy can further reduce the size of the tumor and increase the likelihood of avoiding the side effects of surgery. Palbociclib with letrozole may be a good treatment in the preoperative stage for luminal breast cancer that is resistant to chemotherapy.}, } @article {pmid33828234, year = {2022}, author = {Hu, A and Hong, F and Li, D and Xie, Q and Chen, K and Zhu, L and He, H}, title = {KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.}, journal = {Cancer gene therapy}, volume = {29}, number = {2}, pages = {215-224}, pmid = {33828234}, issn = {1476-5500}, mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; LIM Domain Proteins ; Mice ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.}, } @article {pmid33828068, year = {2021}, author = {Nehmeh, WA and Derienne, J and El Khoury, L and Kassar, S and Track-Smayra, V and Noun, R and Chakhtoura, G}, title = {A 58-Year-Old Woman with Acute Gastric Perforation Due to Metastatic Ductal Carcinoma 18 Years Following Bilateral Mastectomy for Invasive Ductal Carcinoma of the Breast.}, journal = {The American journal of case reports}, volume = {22}, number = {}, pages = {e927094}, pmid = {33828068}, issn = {1941-5923}, mesh = {Breast ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Lobular ; Female ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {BACKGROUND Invasive lobular carcinoma and ductal carcinoma of the breast can metastasize to all sites in the body, including the gastrointestinal tract. Late presentation of metastases of lobular carcinoma of the breast to the gastrointestinal tract have previously been reported, but late metastasis of ductal carcinoma of the breast to the gastric mucosa is rare. This report is of a 58-year-old Lebanese woman who presented with acute gastric perforation due to metastatic ductal carcinoma,18 years following bilateral mastectomy for invasive ductal carcinoma of the breast. CASE REPORT We present the case of a 58-year-old woman who underwent a right modified mastectomy for an invasive ductal carcinoma in 2002 combined with a contralateral prophylactic mastectomy for cosmetic purposes. She presented a secondary gastric lesion 18 years later. The clinical presentation resembled perforated ulcer. The choice of gastrectomy was denied due to retrogastric and pancreatic invasion by the tumor. A laparoscopic gastric closure failed to heal the perforation. A supraumbilical laparotomy incision was performed for the placement of a Pezzer tube in the gastric perforation and the installation of a feeding jejunostomy. CONCLUSIONS This report is of a rare presentation of metastatic ductal carcinoma of the breast to the gastric mucosa associated with gastric perforation that presented 18 years after bilateral mastectomy. This case highlights the importance of obtaining a full past medical history to identify previous primary malignancy, and also is a reminder that ductal carcinoma of the breast can present with metastatic involvement in the gastrointestinal tract several months, or even years, following mastectomy.}, } @article {pmid33827325, year = {2021}, author = {Weaver, KD and Isom, J and Esnakula, A and Daily, K and Asirvatham, JR}, title = {Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.}, journal = {International journal of surgical pathology}, volume = {29}, number = {8}, pages = {882-886}, doi = {10.1177/10668969211008508}, pmid = {33827325}, issn = {1940-2465}, mesh = {Adult ; Anoctamin-1/analysis/metabolism ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Breast/*pathology/surgery ; Carcinoma, Acinar Cell/*diagnosis/genetics/pathology ; DNA Mutational Analysis ; Female ; GATA3 Transcription Factor/analysis/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Mastectomy ; Neoplasm Proteins/analysis/metabolism ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology ; Proto-Oncogene Proteins c-ret/genetics ; Sentinel Lymph Node Biopsy ; Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.}, } @article {pmid33824828, year = {2021}, author = {Khanam, R and Fanous, IS and Fadhel, EN and Hyder, T and Brufsky, A}, title = {Voltage-Gated Calcium Channel Antibody-Induced Oropharyngeal Dysphagia Presenting as a Paraneoplastic Neurological Complication in Breast Cancer.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e13677}, pmid = {33824828}, issn = {2168-8184}, abstract = {Paraneoplastic neurologic syndromes (PNS) are a group of disorders characterized by an autoimmune response against the nervous system due to cross-reactivity between malignant and normal neural tissue. The most commonly associated malignancies include small cell lung cancer, ovarian cancer, breast cancer, and lymphoma. Multiple PNS have been reported including paraneoplastic cerebellar degeneration, retinopathy, sensorimotor peripheral neuropathy, encephalopathy, opsoclonus-myoclonus syndrome, and stiff-person syndrome. We report a case of a 67-year-old woman with breast cancer who presented with a history of progressive oropharyngeal dysphagia as a paraneoplastic neurologic complication. She was diagnosed with invasive ductal carcinoma, nuclear grade 3 with moderate peritumoral lymphoid infiltrate. Hormone receptors were weakly positive for estrogen receptor (ER) (H score 15), weakly positive for progesterone receptor (PR) (H score 30), and negative for human epidermal growth factor receptor 2 (HER-2/NEU). The patient underwent a localized segmental mastectomy but declined any further adjuvant treatment. Three years after being diagnosed with invasive ductal carcinoma of the breast, she developed progressive oropharyngeal dysphagia that warranted percutaneous endoscopic gastrostomy (PEG) tube placement. Testing for onconeural antibodies was positive for voltage-gated calcium channel antibody. An extensive workup was negative for any alternative etiology that would explain her neurological symptoms. The patient declined further treatment and eventually succumbed to her illness.}, } @article {pmid33824803, year = {2021}, author = {Hashmi, AA and Zia, S and Yaqeen, SR and Ahmed, O and Asghar, IA and Islam, S and Afzal, A and Irfan, M and Zia, F and Ali, J}, title = {Mucinous Breast Carcinoma: Clinicopathological Comparison With Invasive Ductal Carcinoma.}, journal = {Cureus}, volume = {13}, number = {3}, pages = {e13650}, pmid = {33824803}, issn = {2168-8184}, abstract = {Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.}, } @article {pmid33824344, year = {2021}, author = {Kricheli-Katz, T and Regev, T}, title = {The effect of language on performance: do gendered languages fail women in maths?.}, journal = {NPJ science of learning}, volume = {6}, number = {1}, pages = {9}, pmid = {33824344}, issn = {2056-7936}, abstract = {Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.}, } @article {pmid33820744, year = {2021}, author = {Vartholomatos, G and Harissis, H and Andreou, M and Tatsi, V and Pappa, L and Kamina, S and Batistatou, A and Markopoulos, GS and Alexiou, GA}, title = {Rapid Assessment of Resection Margins During Breast Conserving Surgery Using Intraoperative Flow Cytometry.}, journal = {Clinical breast cancer}, volume = {21}, number = {5}, pages = {e602-e610}, doi = {10.1016/j.clbc.2021.03.002}, pmid = {33820744}, issn = {1938-0666}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/*surgery ; Female ; Flow Cytometry/*methods ; Humans ; Intraoperative Period ; *Margins of Excision ; Neoplasm Grading ; Reoperation ; }, abstract = {BACKGROUND: Positive margins are the most important factor for recurrence of the disease after breast-conserving surgery. Several methods have been developed throughout the years to evaluate the margin status during surgery in an attempt to assist the surgeon in excising the whole tumor at once, a goal that has not yet been accomplished.

PATIENTS AND METHODS: In our study, we compared intraoperative flow cytometry (iFC) with cytology and pathology in order to evaluate 606 samples of margins and tumors corresponding to 99 patients with invasive ductal carcinoma of no special type and invasive lobular carcinoma obtained from breast-conserving surgeries.

RESULTS: Using the pathology as the gold standard, flow cytometry had 93.3% sensitivity, 92.4% specificity, and 92.5% accuracy. Cytology had 82.3% sensitivity, 94.6% specificity, and 94.2% accuracy.

CONCLUSIONS: Our data support the suggestion that iFC is a novel, reliable technique that allows rapid evaluation of the excision margins of lumpectomies, thus improving the precision of breast-conserving surgery. Among the advantages of iFC are that it does not rely on the expertise of a pathologist or cytologist, it is low cost, and it has no additional psychological effect on patients, because no re-operation is needed.}, } @article {pmid33819733, year = {2021}, author = {Palgi, Y and Bergman, YS and Ben-David, B and Bodner, E}, title = {No psychological vaccination: Vaccine hesitancy is associated with negative psychiatric outcomes among Israelis who received COVID-19 vaccination.}, journal = {Journal of affective disorders}, volume = {287}, number = {}, pages = {352-353}, pmid = {33819733}, issn = {1573-2517}, mesh = {*COVID-19 ; COVID-19 Vaccines ; Cross-Sectional Studies ; Humans ; Israel/epidemiology ; SARS-CoV-2 ; Vaccination ; *Vaccines ; }, abstract = {BACKGROUND: The widespread COVID-19 vaccination program, issued by the Israel Government, provides a unique opportunity to examine psychiatric morbidity and vaccine attitudes among individuals who have already been vaccinated. Accordingly, the current study examined how vaccine hesitancy contributes to clinical levels of depression, anxiety, and peritraumatic stress among individuals who had received COVID-19 vaccinations.

METHODS: We analyzed data obtained from 254 vaccinated individuals, and assessed vaccine hesitancy, depression, anxiety, and peritraumatic distress, as well as several demographic, health, and COVID-19-related factors.

RESULTS: Logistic regressions demonstrated that above and beyond socio-demographic, health, and COVID-19-related factors, COVID-19 vaccine hesitancy was the most prominent risk factor for anxiety, depression, and peritraumatic distress. Higher levels of vaccine hesitancy were found to double the risk for depression and peritraumatic stress (ORs > 2), and to triple the risk for anxiety (OR > 3).

LIMITATIONS: A cross-sectional design; a preliminary study requiring further investigation CONCLUSIONS: This study points to the importance of vaccine hesitancy among vaccinated populations and provides knowledge regarding its associations with negative psychiatric outcomes. These findings may offer important information for healthcare practitioners and policy makers in their attempt to encourage individuals to receive COVID-19 vaccinations and emphasize the need to further understand the underlying mechanisms of psychiatric morbidity among vaccinated individuals.}, } @article {pmid33818021, year = {2021}, author = {Alyami, H and Yoo, TK and Cheun, JH and Lee, HB and Jung, SM and Ryu, JM and Bae, SJ and Jeong, J and Yoon, CI and Ahn, J and Paik, PS and Cho, MK and Park, WC}, title = {Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations.}, journal = {Journal of breast cancer}, volume = {24}, number = {2}, pages = {175-182}, pmid = {33818021}, issn = {1738-6756}, abstract = {PURPOSE: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes; however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations.

METHODS: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea.

RESULTS: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8-222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer.

CONCLUSION: As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2. A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.}, } @article {pmid33816303, year = {2021}, author = {Jiang, X and Wang, X and Shen, T and Yao, Y and Chen, M and Li, Z and Li, X and Shen, J and Kou, Y and Chen, S and Zhou, X and Luo, Z and Cheng, Z}, title = {FAPI-04 PET/CT Using [[18]F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {649148}, pmid = {33816303}, issn = {2234-943X}, abstract = {[68]Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [[18]F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [[18]F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [[18]F]AlF-NOTA-FAPI-04 on patients. [[18]F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [[18]F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [[18]F]AlF-NOTA-FAPI-04 and [18]F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [[18]F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [[18]F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [[18]F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [[18]F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by [18]F-FDG. [[18]F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.}, } @article {pmid33816188, year = {2021}, author = {Xu, M and Tang, Q and Li, M and Liu, Y and Li, F}, title = {An analysis of Ki-67 expression in stage 1 invasive ductal breast carcinoma using apparent diffusion coefficient histograms.}, journal = {Quantitative imaging in medicine and surgery}, volume = {11}, number = {4}, pages = {1518-1531}, pmid = {33816188}, issn = {2223-4292}, abstract = {BACKGROUND: To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC).

METHODS: The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters.

RESULTS: The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05).

CONCLUSIONS: Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.}, } @article {pmid33804802, year = {2021}, author = {Ardila, DC and Aggarwal, V and Singh, M and Chattopadhyay, A and Chaparala, S and Sant, S}, title = {Identifying Molecular Signatures of Distinct Modes of Collective Migration in Response to the Microenvironment Using Three-Dimensional Breast Cancer Models.}, journal = {Cancers}, volume = {13}, number = {6}, pages = {}, pmid = {33804802}, issn = {2072-6694}, support = {R37 CA232209/CA/NCI NIH HHS/United States ; R37CA232209/NH/NIH HHS/United States ; }, abstract = {Collective cell migration is a key feature of transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) among many other cancers, yet the microenvironmental factors and underlying mechanisms that trigger collective migration remain poorly understood. Here, we investigated two microenvironmental factors, tumor-intrinsic hypoxia and tumor-secreted factors (secretome), as triggers of collective migration using three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of DCIS-IDC transition. Interestingly, the two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (600 µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional migration, while small (150 µm), non-hypoxic microtumors exhibited radial migration only when exposed to the secretome of large microtumors. To investigate the mechanisms underlying hypoxia- and secretome-induced directional vs. radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors compared with non-hypoxic, non-migratory small microtumors as controls. We propose unique gene signature sets related to tumor-intrinsic hypoxia, hypoxia-induced epithelial-mesenchymal transition (EMT), as well as hypoxia-induced directional migration and secretome-induced radial migration. Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis revealed enrichment and potential interaction between hypoxia, EMT, and migration gene signatures for the hypoxia-induced directional migration. In contrast, hypoxia and EMT were not enriched in the secretome-induced radial migration, suggesting that complete EMT may not be required for radial migration. Survival analysis identified unique genes associated with low survival rate and poor prognosis in TCGA-breast invasive carcinoma dataset from our tumor-intrinsic hypoxia gene signature (CXCR4, FOXO3, LDH, NDRG1), hypoxia-induced EMT gene signature (EFEMP2, MGP), and directional migration gene signature (MAP3K3, PI3K3R3). NOS3 was common between hypoxia and migration gene signature. Survival analysis from secretome-induced radial migration identified ATM, KCNMA1 (hypoxia gene signature), and KLF4, IFITM1, EFNA1, TGFBR1 (migration gene signature) to be associated with poor survival rate. In conclusion, our unique 3D cultures with controlled microenvironments respond to different microenvironmental factors, tumor-intrinsic hypoxia, and secretome by adopting distinct collective migration modes and their gene expression analysis highlights the phenotypic heterogeneity and plasticity of epithelial cancer cells.}, } @article {pmid33795819, year = {2021}, author = {Nagasawa, S and Kuze, Y and Maeda, I and Kojima, Y and Motoyoshi, A and Onishi, T and Iwatani, T and Yokoe, T and Koike, J and Chosokabe, M and Kubota, M and Seino, H and Suzuki, A and Seki, M and Tsuchihara, K and Inoue, E and Tsugawa, K and Ohta, T and Suzuki, Y}, title = {Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {438}, pmid = {33795819}, issn = {2399-3642}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Female ; GATA3 Transcription Factor/genetics/metabolism ; *Gene Amplification ; Gene Expression Profiling ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/genetics/metabolism ; Young Adult ; }, abstract = {In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.}, } @article {pmid33790186, year = {2021}, author = {Yamamoto, D and Yamamoto, C and Okugawa, H and Tsubota, Y and Kawakami, K}, title = {[The Treatment of Olaparib for BRCA Positive-Metastatic Breast Cancer Patient].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {3}, pages = {455-456}, pmid = {33790186}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Neoadjuvant Therapy ; Phthalazines ; Piperazines ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {Breast cancer patient(invasive ductal carcinoma, ER[+], PgR[+], HER2[3+], Ki-67: 30%)had neoadjuvant chemotherapy(FEC followed by docetaxel plus trastuzumab). After surgical operation(mastectomy and Ax)was performed and she received trastuzumab plus hormone therapy. After 2 years later, she had liver metastasis that showed IDC, ER(+), PgR (+), HER2(-). In addition, BRCA positive was shown. Therefore, the patient received olaparib tablets(300 mg twice daily). After 2 months later, liver metastasis reduced dramatically.}, } @article {pmid33790181, year = {2021}, author = {Satoh, E and Uchiyama, D and Uehira, D and Yonekura, K and Murakata, A and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Useful Method of Nipple-Side HydroMARK-Marking before Neoadjuvant Chemotherapy in the Breast Preserving Surgery-A Case Report with pCR of the Triple Negative Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {3}, pages = {440-442}, pmid = {33790181}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Nipples/surgery ; Receptor, ErbB-2 ; Treatment Outcome ; *Triple Negative Breast Neoplasms/drug therapy/surgery ; }, abstract = {When the primary breast cancer disappears by neoadjuvant chemotherapy, it is often difficult to detect it during the breast preserving surgery. Before neoadjuvant chemotherapy, preoperative nipple-side HydroMARK-marking, which was made of titanium coil and hydrogel, was a very useful and effective method because of its fine detection by ultrasonography. We report a case of 51-year-old female with the triple negative breast cancer(TNBC). At first, the HydroMARK was inserted between the nipple and the tumor. Its distance was about 10 mm toward the nipple. EC therapy followed by docetaxel was performed for 6 months as neoadjuvant chemotherapy. After that, her left TNBC(T1N0M0, Stage Ⅰ, invasive ductal carcinoma, ER[-], PgR[-], HER2[-])was disappeared in all imagings and resected in August 2018. The HydroMARK was clearly detected by intraoperative ultrasonography and her right breast preserving surgery was completely performed. Its pathological finding was pCR(pathological complete response).}, } @article {pmid33790169, year = {2021}, author = {Kimura, A and Hashimoto, N and Sawano, T and Yamamoto, T and Yamauchi, Y and Kagiya, T and Ohashi, M and Kato, M and Umehara, Y and Nishikawa, S and Murata, A and Takahashi, K}, title = {[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {3}, pages = {403-406}, pmid = {33790169}, issn = {0385-0684}, mesh = {*Breast Neoplasms/surgery ; Esophagectomy ; Female ; Humans ; *Laparoscopy ; Mastectomy ; Retrospective Studies ; }, abstract = {Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.}, } @article {pmid33790164, year = {2021}, author = {Ishikawa, H and Kouki, T and Oda, R and Midorikawa, R and Kojima, S and Kinoe, H and Kishimoto, Y and Okabe, M and Hosokawa, Y and Okazaki, T and Tayama, K and Kosuga, K and Ogou, E and Akiba, J and Yano, H}, title = {Neoadjuvant Hyperthermia and Chemoradiotherapy for Borderline Resectable Pancreatic Cancer.}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {3}, pages = {388-390}, pmid = {33790164}, issn = {0385-0684}, mesh = {Aged, 80 and over ; *Carcinoma, Pancreatic Ductal ; Chemoradiotherapy ; Humans ; Hyperthermia ; Male ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/drug therapy ; Tumor Microenvironment ; }, abstract = {Pancreatic cancer(PC)is associated with poor prognosis and low resectability rates. Currently, only 15-20% of all patients are candidates for upfront surgery at the time of diagnosis, which offers the chance of long-term survival. In recent years, patients with borderline resectable PC(BR-PC)have been treated with surgery following neoadjuvant chemoradiotherapy or intensive multi-agent chemotherapy. In PC, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of chemo(radio)therapy. An 84-year-old man with fatty stool was diagnosed with pancreatic head cancer according to the result of contrast computed tomography(CT), which showed a 37 mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric artery(SMA)plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was BR-PC, cT3, N0, M0, cStage Ⅱ A. The patient was treated with hyperthermia plus S-1 and radiotherapy. The size of the tumor had reduced from 37 mm to 15 mm after the neoadjuvant therapy, and the infiltration into the SMA plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)concomitant resection of the PV, SMV, SV confluence. The histopathological findings were invasive ductal carcinoma with R0 radical resection. There has been no recurrence 18 months after the surgery. Based on the above-mentioned findings, hyperthermia and chemoradiotherapy can be an effective option of neoadjuvant treatment for BR-PC.}, } @article {pmid33785437, year = {2021}, author = {Garcia, AM and Bishop, EL and Li, D and Jeffery, LE and Garten, A and Thakker, A and Certo, M and Mauro, C and Tennant, DA and Dimeloe, S and Evelo, CT and Coort, SL and Hewison, M}, title = {Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {211}, number = {}, pages = {105891}, pmid = {33785437}, issn = {1879-1220}, support = {MR/T016736/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Adipogenesis ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/*metabolism ; Fatty Acids/*biosynthesis ; Glycolysis ; Humans ; *Immune Tolerance ; Vitamin D/*analogs & derivatives/pharmacology ; }, abstract = {The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of immune function, promoting anti-inflammatory, tolerogenic T cell responses by modulating antigen presentation by dendritic cells (DC). Transcriptomic analyses indicate that DC responses to 1,25D involve changes in glycolysis, oxidative phosphorylation, electron transport and the TCA cycle. To determine the functional impact of 1,25D-mediated metabolic remodelling, human monocyte-derived DC were differentiated to immature (+vehicle, iDC), mature (+LPS, mDC), and immature tolerogenic DC (+1,25D, itolDC) and characterised for metabolic function. In contrast to mDC which showed no change in respiration, itolDC showed increased basal and ATP-linked respiration relative to iDC. Tracer metabolite analyses using [13]C -labeled glucose showed increased lactate and TCA cycle metabolites. Analysis of lipophilic metabolites of [13]C-glucose revealed significant incorporation of label in palmitate and palmitoleate, indicating that 1,25D promotes metabolic fatty acid synthesis in itolDC. Inhibition of fatty acid synthesis in itolDC altered itolDC morphology and suppressed expression of CD14 and IL-10 by these cells. These data indicate that the ability of 1,25D to induce tolerogenic DC involves metabolic remodelling leading to synthesis of fatty acids.}, } @article {pmid33779370, year = {2021}, author = {Gaertner, KM and Poornima, IG and Hilton, C}, title = {Trastuzumab and pertuzumab in hemodialysis: A case report.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {27}, number = {7}, pages = {1799-1801}, doi = {10.1177/10781552211003641}, pmid = {33779370}, issn = {1477-092X}, mesh = {Antibodies, Monoclonal, Humanized ; *Antineoplastic Combined Chemotherapy Protocols ; Female ; Humans ; Renal Dialysis ; Stroke Volume ; Trastuzumab/therapeutic use ; *Ventricular Function, Left ; }, abstract = {INTRODUCTION: Trastuzumab and pertuzumab are recombinant humanized monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2). Currently, six reported cases on the use of trastuzumab in dialysis, and one on the use of pertuzumab, have been identified in the literature. This case is one of the first to describe the use of pertuzumab, and adds to currently available reports on the use of trastuzumab, in hemodialysis.

CASE REPORT: A female receiving hemodialysis three times per week was diagnosed with a clinical T2N1M0, hormone receptor-negative, HER2-positive, invasive ductal carcinoma of the breast. She received six cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, with left ventricular ejection fraction (LVEF) remaining stable throughout. Following surgery, she continued dual HER2 blockade with trastuzumab and pertuzumab, after six cycles of which she was found on routine echocardiogram to have an asymptomatic decline in LVEF.Management & outcome: Following the decline in LVEF, trastuzumab and pertuzumab were held, and cardio-oncology was consulted. LVEF recovered within one month, after which she continued on single-agent trastuzumab to complete one year of HER2-directed therapy.

DISCUSSION: To our knowledge, this is one of the first published cases describing the use of pertuzumab in a patient receiving hemodialysis. Though our patient did experience a reversible decline in LVEF following twelve cycles of combination trastuzumab and pertuzumab, this case demonstrates the relatively safe and effective use of pertuzumab in a patient with end-stage renal disease undergoing hemodialysis, and lends additional support to the use of trastuzumab in this particular patient population.}, } @article {pmid33778749, year = {2020}, author = {Komoroski, RA and Lee, JH and Welge, JA and Dudley, JA and Chu, WJ and Mahoney, MC}, title = {[1]H MR Spectroscopy of Fine-Needle Aspiration Biopsy Specimens for the Discrimination of Breast Cancer.}, journal = {Radiology. Imaging cancer}, volume = {2}, number = {6}, pages = {e200033}, pmid = {33778749}, issn = {2638-616X}, mesh = {Biopsy, Fine-Needle ; Breast ; *Breast Neoplasms/diagnosis ; Female ; Humans ; *Magnetic Resonance Spectroscopy ; Middle Aged ; Prospective Studies ; }, abstract = {PURPOSE: To determine whether MR spectroscopic assessment of fine-needle aspiration (FNA) biopsy specimens from suspicious breast lesions could be used to improve the diagnostic utility of FNA biopsies for the characterization of breast lesions.

MATERIALS AND METHODS: In this prospective study, a previously reported technique using high-spatial-resolution proton MR spectroscopy was modified and used to examine the utility of FNA biopsies in the evaluation of suspicious breast lesions. Tissue samples from 115 lesions (from 102 women; average age, 54 years) were excised by using FNA and core biopsies and were collected between September 7, 2012, and April 11, 2014. Histologic results from core biopsy specimens determined the lesions to be benign (n = 55), invasive ductal carcinoma (n = 51), invasive lobular carcinoma (n = 5), or ductal carcinoma in situ (n = 4). Measures of phosphocholine (PC), glycerophosphocholine, and choline relative to each other and to total creatine (tCr) were obtained from usable spectra. Planned comparisons among lesion groups were carried out using t test contrasts, and differences of each contrast level from zero were judged significant when the two-tailed P value was less than .05.

RESULTS: Of the 115 samples, 69 (60%) yielded no usable MR spectra. Analysis of the 46 with usable spectra found that only the difference in PC/tCr between benign and cancer lesions was statistically significant (P = .028).

CONCLUSION: Given that 60% of FNA biopsy specimens yielded no usable spectra and that results were largely inconclusive when derived from usable spectra, the combined MR and FNA technique, as modified and implemented in this study, is of little value for detection and diagnosis of breast cancer.Keywords: Breast, MR-Spectroscopy, Neoplasms-Primary© RSNA, 2020.}, } @article {pmid33777568, year = {2021}, author = {Hashmi, AA and Munawar, S and Rehman, N and Ahmed, O and Islam, S and Asghar, IA and Afzal, A and Irfan, M and Shamail, F and Ali, SJ}, title = {Invasive Papillary Carcinoma of the Breast: Clinicopathological Features and Hormone Receptor Profile.}, journal = {Cureus}, volume = {13}, number = {2}, pages = {e13480}, pmid = {33777568}, issn = {2168-8184}, abstract = {Introduction Papillary neoplasms are a heterogeneous group of breast lesions, ranging from benign to in situ and invasive malignant tumors. The term invasive papillary carcinoma (IPC) is reserved for rare invasive breast tumors showing greater than 90% papillary morphology. The clinical, epidemiological and pathological characteristics of IPC are not widely described in the existing literature; therefore, in this study, we evaluated the clinicopathological features and biomarker profile of IPC and compared it with invasive ductal carcinoma (IDC) diagnosed in the same study duration. Methods A retrospective study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 to December 2020. During the study period, 44 cases of IPC and 1,268 cases of IDC were diagnosed. Slides and blocks of all cases were retrieved and histopathological diagnosis was reviewed. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), and Ki67 immunohistochemical (IHC) stains were applied on representative tissue blocks. Results The mean age of the patients with IPC was 58.77±8.38 years, and the mean Ki67 index was 19.95±21.12%. The mean tumor size was 32.41±17.39 mm, and most tumors (59.1%) were tumor (T)-stage T2. Axillary metastasis was present in 13.6% cases, and 86.4% cases had nodal (N)-stage N0. ER and PR expression was noted in 72.7% cases, and HER2/neu positivity was seen in 13.6% cases. IPC cases had a higher mean age than IDC. Conversely, IPC had a lower mean Ki67 index than IDC. Similarly, IPC cases were found to have a lower frequency of axillary metastasis than IDC. IPC was noted to have a lower frequency of T3-stage and lymphovascular invasion than IDC. A higher expression of PR and lower frequency of HER2/neu expression was noted in IPC than IDC. Conclusion IPC is a rare malignant papillary breast tumor with a wide differential diagnosis and therefore poses a significant diagnostic challenge. We found that IPC had a favorable pathological profile than IDC, in terms of T-stage, Ki67 index, axillary metastasis, PR and HER2/neu expression.}, } @article {pmid33776732, year = {2021}, author = {Sugimoto, H and Oda, G and Yokoyama, M and Hayashi, K and Yoshino, M and Ogawa, A and Hosoya, T and Nakagawa, T and Uetake, H}, title = {Hydronephrosis Caused by Metastatic Breast Cancer.}, journal = {Case reports in oncology}, volume = {14}, number = {1}, pages = {378-385}, pmid = {33776732}, issn = {1662-6575}, abstract = {Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.}, } @article {pmid33776729, year = {2021}, author = {Al-Gahmi, A and Alhuthali, M and Alrehaili, M and Baltow, B and Tashkandi, E}, title = {Unusual Synchronous Association of Solid Tumors with Hematological Malignancies in Multiple Primary Cancers: Case Series and Literature Review.}, journal = {Case reports in oncology}, volume = {14}, number = {1}, pages = {352-364}, pmid = {33776729}, issn = {1662-6575}, abstract = {The incidence of synchronous multiple primary malignancies (MPMs), which include both solid and hematological malignancy, is considered very rare. In addition, the involvement of sites such as brain, thyroid, and breast are among the least reported in such complex conditions. Here we report five different types of solid tumors including glioblastoma multiforme, thyroid papillary carcinoma, breast invasive ductal carcinoma, colon cancer, and gastric adenocarcinoma that were associated with synchronous five different hematological malignancies in the form of T-cell lymphoblastic non-Hodgkin lymphoma (NHL), nodal marginal zone NHL, diffuse large B-cell NHL, Hodgkin lymphoma, and gastric mucosa-associated lymphoid tissue marginal zone NHL, respectively. The diagnosis of MPMs can be challenging, and there is no standard treatment for such difficult primary malignancies. However, the management of these conditions should be individualized using tumor board discussion and ensuring multidisciplinary coordinated care, besides considering treatment of the more aggressive malignancy before that with the less malignant potential.}, } @article {pmid33768925, year = {2021}, author = {Ali, EA and Elmalik, H and Omar, NE and Yassin, MA}, title = {Invasive ductal breast carcinoma preceded by CALR-positive essential thrombocythemia.}, journal = {Clinical case reports}, volume = {9}, number = {3}, pages = {1732-1736}, pmid = {33768925}, issn = {2050-0904}, abstract = {Persistent thrombocytosis in patients with cancer needs workup because it can be linked to essential thrombocytosis. The management should be individualized to start treatment for low-risk essential thrombocytosis due to the combined risk of thrombosis.}, } @article {pmid33768733, year = {2022}, author = {Teh, J and Dessauvagie, B and Kessell, M and Dissanayake, D and Wylie, EJ}, title = {An atypically located pleomorphic adenoma: Radiological and pathological correlation.}, journal = {Journal of medical imaging and radiation oncology}, volume = {66}, number = {1}, pages = {105-106}, doi = {10.1111/1754-9485.13178}, pmid = {33768733}, issn = {1754-9485}, mesh = {*Adenoma, Pleomorphic/diagnostic imaging/surgery ; *Breast Neoplasms ; Female ; Humans ; Middle Aged ; Radiography ; *Salivary Gland Neoplasms/diagnostic imaging ; }, abstract = {Pleomorphic adenoma is a common benign salivary gland neoplasm which very rarely occurs in the breast. Its radiologic and pathologic appearance may be mistaken for other benign or malignant lesions such as a fibroadenoma or invasive ductal carcinoma. Due to the risk of local recurrence and, rarely, malignant transformation, wide local excision with clear margins is recommended. As such, a correct diagnosis of this lesion is important to ensure appropriate surgical treatment. We report a case of an atypically located pleomorphic adenoma with radiologic-pathologic correlation in an asymptomatic 63-year-old woman.}, } @article {pmid33764299, year = {2021}, author = {Shimon-Raz, O and Salomon, R and Bloch, M and Aisenberg Romano, G and Yeshurun, Y and Ulmer Yaniv, A and Zagoory-Sharon, O and Feldman, R}, title = {Mother brain is wired for social moments.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33764299}, issn = {2050-084X}, mesh = {Adult ; Brain/*diagnostic imaging ; Cross-Over Studies ; Double-Blind Method ; Female ; Humans ; *Magnetic Resonance Imaging ; Mothers/*psychology ; *Neuroimaging ; *Parent-Child Relations ; *Social Interaction ; Young Adult ; }, abstract = {Reorganization of the maternal brain upon childbirth triggers the species-typical maternal social behavior. These brief social moments carry profound effects on the infant's brain and likely have a distinct signature in the maternal brain. Utilizing a double-blind, within-subject oxytocin/placebo administration crossover design, mothers' brain was imaged twice using fMRI while observing three naturalistic maternal-infant contexts in the home ecology; 'unavailable', 'unresponsive', and 'social', when mothers engaged in synchronous peek-a-boo play. The social condition elicited greater neural response across the human caregiving network, including amygdala, VTA, hippocampus, insula, ACC, and temporal cortex. Oxytocin impacted neural response primarily to the social condition and attenuated differences between social and non-social stimuli. Greater temporal consistency emerged in the 'social' condition across the two imaging sessions, particularly in insula, amygdala, and TP. Findings describe how mother's brain varies by caregiving experiences and gives salience to moments of social synchrony that support infant development and brain maturation.}, } @article {pmid33763866, year = {2021}, author = {Garg, KK and Anantha, KH and Venkataradha, A and Dixit, S and Singh, R and Ragab, R}, title = {Impact of Rainwater Harvesting on Hydrological Processes in a Fragile Watershed of South Asia.}, journal = {Ground water}, volume = {59}, number = {6}, pages = {839-855}, doi = {10.1111/gwat.13099}, pmid = {33763866}, issn = {1745-6584}, mesh = {Asia ; *Ecosystem ; *Groundwater ; Hydrology ; Soil ; }, abstract = {Agricultural water management (AWM) interventions play an important role in ensuring sustainable food production and mitigating climate risks. This study was carried out in a watershed located in a low rainfall (400-600 mm) region of western India. The Soil and Water Assessment Tool model was calibrated using surface runoff, soil loss, and reservoir storage levels, between the year 2000 and 2006. The investigation indicated that the various AWM interventions increased groundwater recharge from 30 mm/year to 80 mm/year and reduced surface runoff from 250 mm/year to 100 mm/year. The intervention structures were refilled two to three times during the monsoon season depending on rainfall intensity and duration. The interventions have the advantage of building a resilient system by enhancing groundwater availability even in dry years, stimulating crop intensification and protecting the landscape from severe erosion. The results indicate that soil erosion has been reduced by more than 75% compared to the nonintervention situation. Moreover, the AWM interventions led to the cultivation of 100-150 ha of fallow land with high-value crops (horticulture, vegetables, and fodder). Household income increased by several folds compared to the nonintervention situation. The study showed about 50% reduction in downstream water availability, which could be a major concern. However, there are a number of ecosystem trade-offs such as improved base flow to the stream and reduction in soil loss that should be considered. The study is of great importance to stakeholders to decide on the optimal design for AWM interventions to achieve sustainable development goals.}, } @article {pmid33761962, year = {2021}, author = {Rodrigues, MA and Caldeira-Brant, AL and Gomes, DA and Silveira, TL and Chiarini-Garcia, H and Cassali, GD}, title = {Characterization of neoplastic cells outlining the cystic space of invasive micropapillary carcinoma of the canine mammary gland.}, journal = {BMC veterinary research}, volume = {17}, number = {1}, pages = {130}, pmid = {33761962}, issn = {1746-6148}, mesh = {Animals ; Biomarkers, Tumor/metabolism ; Carcinoma, Papillary/metabolism/pathology/*veterinary ; Dog Diseases/metabolism/*pathology ; Dogs ; Female ; Fluorescent Antibody Technique/veterinary ; Immunohistochemistry/veterinary ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Animal/metabolism/*pathology ; Microscopy, Electron, Transmission/veterinary ; Phenotype ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC.

RESULTS: Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs. Cells expressing the mesenchymal markers alpha-smooth muscle actin (αSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples. Furthermore, associated with peculiar morphology, such as thin cytoplasmic extensions outlining cystic spaces, was observed under TEM. These observations suggested cells with characteristics of myoepithelial-like cells.

CONCLUSIONS: The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing αSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.}, } @article {pmid33759587, year = {2021}, author = {Martens, TW and Lima, JS and Johnson, EA and Conry, JA and Hoppe, JJ and Bergenstal, RM and Carlson, AL and Davidson, JL}, title = {Trial of a New Diabetes Education Model: Closing the Gap in Health Disparity for People with Diabetes.}, journal = {Journal of diabetes science and technology}, volume = {15}, number = {3}, pages = {568-574}, pmid = {33759587}, issn = {1932-2968}, mesh = {Delivery of Health Care ; *Diabetes Mellitus/therapy ; Glycated Hemoglobin/analysis ; Humans ; Pilot Projects ; Quality Improvement ; }, abstract = {BACKGROUND: Quality measures relating to diabetes care in America have not improved between 2005 and 2016, and have plateaued even in areas that outperform national statistics. New approaches to diabetes care and education are needed and are especially important in reaching populations with significant barriers to optimized care.

METHODS: A pilot quality improvement study was created to optimize diabetes education in a clinic setting with a patient population with significant healthcare barriers. Certified Diabetes Care and Education Specialists (CDCES) were deployed in a team-based model with flexible scheduling and same-day education visits, outside of the traditional framework of diabetes education, specifically targeting practices with underperforming diabetes quality measures, in a clinic setting significantly impacted by social determinants of health.

RESULTS: A team-based and flexible diabetes education model decreased hemoglobin A1C for individuals participating in the project (and having a second A1C measured) by an average of -2.3%, improved Minnesota Diabetes Quality Measures (D5) for clinicians participating in the project by 5.8%, optimized use of CDCES, and reduced a high visit fail rate for diabetes education.

CONCLUSIONS: Diabetes education provided in a team-based and flexible model may better meet patient needs and improve diabetes care metrics, in settings with a patient population with significant barriers.}, } @article {pmid33759307, year = {2021}, author = {Zhang, J and Zhou, B and Sun, J and Chen, H and Yang, Z}, title = {Betulin ameliorates 7,12-dimethylbenz(a)anthracene-induced rat mammary cancer by modulating MAPK and AhR/Nrf-2 signaling pathway.}, journal = {Journal of biochemical and molecular toxicology}, volume = {35}, number = {7}, pages = {e22779}, doi = {10.1002/jbt.22779}, pmid = {33759307}, issn = {1099-0461}, mesh = {9,10-Dimethyl-1,2-benzanthracene/*toxicity ; Animals ; Female ; MAP Kinase Signaling System/*drug effects ; Mammary Neoplasms, Animal/chemically induced/drug therapy/*metabolism/pathology ; NF-E2-Related Factor 2/*metabolism ; Neoplasm Proteins/*metabolism ; Rats ; Receptors, Aryl Hydrocarbon/*metabolism ; Triterpenes/*pharmacology ; }, abstract = {The aim of the present study is to explore the preventive efficacy of betulin (BE) in 7,12-dimethylbenz(a)anthracene (DMBA)-administered mammary cancer by modulating Ahr/Nrf2 signaling in experimental models. The mammary cancer was stimulated by the addition of DMBA (25 mg/kg/b.Wt) mixed in 1 ml of vehicle solution (sunflower oil and saline 1:1) through subcutaneous injection. The DMBA-exposed mammary tumor models showed low bodyweight, elevated quantities of lipid peroxidation molecules (TBARS and LOOH), and low enzymatic (GPx, SOD, and CAT), and nonenzymatic (GSH, vitamin C, and vitamin E) antioxidant activities in plasma and mammary tissues. Moreover, histopathological studies confirmed that invasive ductal carcinoma was observed in DMBA-induced mammary tissue of the experimental model. Dietary oral supplementation of BE prevents the loss of bodyweight, overproduces lipid peroxidation, and restores the antioxidant activities in DMBA-exposed experimental animals. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial antioxidant protein that involves preventing numerous cancers. Therefore, Nrf2-associated signaling concern is a significant target for preventing mammary cancer. This study observed an increased expression of MAPKs, Keap1, ARNT, AhR, and CYP1A1, whereas decreased expression of HO-1 and Nrf2 in DMBA-induced cancer-bearing experimental animals. The oral supplementation of BE effectively modulates the expression of MAPKs, AhR/Nrf2-associated protein expressions in DMBA-exposed experimental animals. This current study concluded that BE is a strong antioxidant, which triggers the MAPKs-mediated oxidative stress and inhibits proliferative markers by restoring the activity of Nrf2 signaling.}, } @article {pmid33758419, year = {2021}, author = {Okun, JG and Rusu, PM and Chan, AY and Wu, Y and Yap, YW and Sharkie, T and Schumacher, J and Schmidt, KV and Roberts-Thomson, KM and Russell, RD and Zota, A and Hille, S and Jungmann, A and Maggi, L and Lee, Y and Blüher, M and Herzig, S and Keske, MA and Heikenwalder, M and Müller, OJ and Rose, AJ}, title = {Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.}, journal = {Nature metabolism}, volume = {3}, number = {3}, pages = {394-409}, pmid = {33758419}, issn = {2522-5812}, mesh = {Alanine/blood/*metabolism ; Alanine Transaminase/blood ; Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/*metabolism/pathology ; Disease Models, Animal ; Homeostasis ; Humans ; Hyperglycemia/*metabolism ; Liver/*metabolism ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*pathology ; Muscular Atrophy/*metabolism ; Obesity/metabolism ; }, abstract = {Both obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. We find that expression of alanine aminotransferases is increased in the liver in mice with obesity and diabetes, as well as in humans with type 2 diabetes. Hepatocyte-selective silencing of both alanine aminotransferase enzymes in mice with obesity and diabetes retards hyperglycaemia and reverses skeletal muscle atrophy through restoration of skeletal muscle protein synthesis. Mechanistically, liver alanine catabolism driven by chronic glucocorticoid and glucagon signalling promotes hyperglycaemia and skeletal muscle wasting. We further provide evidence for amino acid-induced metabolic cross-talk between the liver and skeletal muscle in ex vivo experiments. Taken together, we reveal a metabolic inter-tissue cross-talk that links skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.}, } @article {pmid33756165, year = {2021}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Bilateral nipple-sparing mastectomy and breast reconstruction in BRCA1 mutation-positive simultaneous bilateral breast cancer: A case study.}, journal = {International journal of surgery case reports}, volume = {81}, number = {}, pages = {105788}, pmid = {33756165}, issn = {2210-2612}, abstract = {BACKGROUND: Mutation-positive patients who develop unilateral breast cancer require different treatments, such as prophylactic mastectomy of the contralateral breast, from those used for other breast cancer patients. If a mutation is found before surgery, it is necessary to consider a surgical procedure that includes reconstruction. For BRCA mutation-positive patients, a suitable treatment must be selected. In Japan, a test for BRCA mutation has been covered by health insurance since 2020, making it possible to preoperatively test patients who are suspected of being positive. We report a case of simultaneous bilateral breast cancer that was found to be BRCA mutation-positive preoperatively and underwent bilateral subcutaneous mastectomy and breast reconstruction.

CASE PRESENTATION: A 57-year-old woman was admitted to our hospital after a breast cancer screening revealed a mass in the left breast. She had a family history of breast cancer, including her sister, aunt, and cousin. She was suspected of being malignant with a mass on both sides of her breast on imaging. She underwent needle biopsy and was diagnosed as having bilateral invasive ductal carcinoma, for which she was placed on preoperative chemotherapy. Due to the strong family history of bilateral breast cancer, the patient was recommended to undergo a BRCA gene-mutation test and she consented. The result was positive for BRCA1 mutation. Although it was judged that bilateral breast-conserving surgery was sufficiently possible, bilateral subcutaneous mastectomy and breast reconstruction were performed based on BRCA mutation-positive status.

DISCUSSION: Performing a preoperative BRCA test may change the surgical procedure. BRCA tests are beneficial to patients, but the timing of the tests is important. Care must be taken not to force the patient.

CONCLUSIONS: Knowing whether the patient is BRCA mutation-positive is extremely important for selecting surgical procedures and treatment methods. BRCA testing should be recommended for patients who are strongly suspected of being positive, but the decision should be the patient's. It is therefore necessary to provide accurate information and engage in a dialogue with the patient, but the medical staff should not pressure the patient to have the test.}, } @article {pmid33753865, year = {2021}, author = {Bergeron, A and MacGrogan, G and Bertaut, A and Ladoire, S and Arveux, P and Desmoulins, I and Bonnefoi, H and Loustalot, C and Auriol, S and Beltjens, F and Degrolard-Courcet, E and Charon-Barra, C and Richard, C and Boidot, R and Arnould, L}, title = {Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {34}, number = {7}, pages = {1282-1296}, pmid = {33753865}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Lobular/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Female ; Humans ; Middle Aged ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/*genetics ; Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology ; }, abstract = {Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma (TN-IDC) and hormone receptor-positive invasive lobular carcinoma (HR + ILC). All primary TN-ILCs registered in our database between 2000 and 2018 (n = 38) were compared to tumors from control groups, matched by stage and Elston/Ellis grade, with regard to clinical, pathologic, and immunohistochemical characteristics. A comparative molecular analysis (whole-exome and RNA sequencing using next-generation technology) was also performed. We found that TN-ILC patients were older than those with HR + ILC (P = 0.002) or TN-IDC (P < 0.001). Morphologically, TN-ILCs had aggressive phenotypes, with more pleomorphism (P = 0.003) and higher nuclear grades than HR + ILCs (P = 0.009). Immunohistochemistry showed that TN-ILCs less frequently expressed basal markers (CK5/6, EGFR and SOX10) than TN-IDCs (P < 0.001), while androgen receptor (AR) positivity was more prevalent (P < 0.001). Survival curves analysis did not show differences between TN-ILC and TN-IDC patients, while overall and distant metastasis-free survival were significantly worse compared to those with HR + ILCs (P = 0.047 and P = 0.039, respectively). At a molecular level, we found that TN-ILCs had particular transcriptomic profiles, characterized by increased AR signaling, and associated with frequent alterations in the PI3K network and ERBB2. Interestingly, whole-exome analysis also identified three specific recurrent ESRRA hotspot mutations in these tumors, which have never been described in breast cancer to date and which were absent in the other two tumor subtypes. Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.}, } @article {pmid33752581, year = {2021}, author = {Nakash, O and Cruz-Gonzalez, M and Lincoln, AK and Banerjee, S and Alegría, M}, title = {Similarities in client-clinician perceptions of subjective social status and its association to similarities in the quality of working alliance and client anxiety symptoms.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {31}, number = {8}, pages = {1079-1091}, doi = {10.1080/10503307.2021.1900618}, pmid = {33752581}, issn = {1468-4381}, mesh = {Anxiety/therapy ; Humans ; Perception ; *Professional-Patient Relations ; *Psychological Distance ; Psychotherapy ; }, abstract = {Subjective social status (SSS) has largely been ignored within psychotherapy literature. We investigated the association between similarities in client-clinician perceptions of SSS, similarities in their report of the quality of working alliance, and resultant anxiety symptoms. Participants represented a primarily low-income, culturally diverse sample of 312 clients receiving care from 68 clinicians at 13 outpatient mental health clinics in the Northeastern United States between September 2013 and August 2016. As part of a larger randomized controlled trial, clients and clinicians completed the MacArthur Scale of subjective social status and the Working Alliance Inventory (WAI), and clients completed the Generalized Anxiety Disorder 7-item Scale (GAD-7). At the within-clinician level, client-clinician dyads with less similar perceptions of the client's SSS were characterized by less similar perceptions of their alliance, which in turn resulted in worsening anxiety symptoms. Clinicians' correct perception of their clients' social status might be important for sharing a similar view of the client-clinician level of alliance, which can, in turn, contribute to lowering the client's anxiety symptoms.}, } @article {pmid33751160, year = {2021}, author = {Zhu, Z and Chen, C and Chen, C and Yan, Z and Chen, F and Yang, B and Zhang, H and Han, H and Lv, X}, title = {Prediction of tumor size in patients with invasive ductal carcinoma using FT-IR spectroscopy combined with chemometrics: a preliminary study.}, journal = {Analytical and bioanalytical chemistry}, volume = {413}, number = {12}, pages = {3209-3222}, pmid = {33751160}, issn = {1618-2650}, support = {This work was supported by Graduate Student Innova//Graduate Student Innovation Project of Xinjiang Uygur Autonomous Region/ ; }, mesh = {Algorithms ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal/*diagnostic imaging/metabolism/pathology ; Female ; Humans ; Models, Biological ; *Neoplasm Invasiveness ; Neural Networks, Computer ; Principal Component Analysis ; Spectroscopy, Fourier Transform Infrared/*methods ; Support Vector Machine ; }, abstract = {Precise detection of tumor size is essential for early diagnosis, treatment, and evaluation of the prognosis of breast cancer. However, there are some errors between the tumor size of breast cancer measured by conventional imaging methods and the pathological tumor size. Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer. In this study, serum Fourier transform infrared spectroscopy (FT-IR) combined with chemometric methods was used to predict the maximum diameter and maximum vertical diameter of tumors in IDC patients. Three models were evaluated based on the pathological tumor size measured after surgery and included grid search support vector machine regression (GS-SVR), back propagation neural network optimized by genetic algorithm (GA-BP-ANN), and back propagation neural network optimized by particle swarm optimization (PSO-BP-ANN). The results show that three models can accurately predict tumor size. The GA-BP-ANN model provided the best fitting quality of the largest tumor diameter with the determination coefficients of 0.984 in test set. And the GS-SVR model provided the best fitting quality of the largest vertical tumor diameter with the determination coefficients of 0.982 in test set. The GS-SVR model had the highest prediction efficiency and the lowest time complexity of the models. The results indicate that serum FT-IR spectroscopy combined with chemometric methods can predict tumor size in IDC patients. In addition, compared with traditional imaging methods, we found that the experimental results of the three models are better than traditional imaging methods in terms of correlation and fitting degree. And the average fitting error of PSO-BP-ANN and GA-BP-ANN models was less than 0.3 mm. The minimally invasive detection method is expected to be developed into a new clinical diagnostic method for tumor size estimation to reduce the diagnostic trauma of patients and provide new diagnostic experience for patients. Graphical Abstract.}, } @article {pmid33749417, year = {2022}, author = {Shenkman, G and Ifrah, K and Shmotkin, D}, title = {The moderation of socio-demographics in physical and mental health disparities among Israeli gay and heterosexual middle-aged and older men.}, journal = {Aging & mental health}, volume = {26}, number = {5}, pages = {1061-1068}, doi = {10.1080/13607863.2021.1901259}, pmid = {33749417}, issn = {1364-6915}, mesh = {Aged ; Demography ; *Heterosexuality/psychology ; Humans ; Israel/epidemiology ; Male ; Mental Health ; Middle Aged ; *Sexual and Gender Minorities ; }, abstract = {OBJECTIVES: Physical and mental health disparities were explored among Israeli middle-aged and older gay and heterosexual men alongside the moderating role of age, relationship status, and place of birth.

METHOD: 173 middle-aged and older gay men were individually matched with 173 middle-aged and older heterosexual men at the age range of 50-86 (M = 60.56, SD = 8.42). All participants completed measures of doctor visits, physical health comorbidity, depressive symptoms, and anxiety.

RESULTS: Israeli middle-aged and older gay and heterosexual men did not significantly differ on physical or mental health indicators. However, a more differential analysis revealed that older age and relationship status had a moderating role, such that older gay men reported more physical health comorbidity in comparison to older heterosexual men. Similarly, gay men who were not in a steady relationship reported more frequent visits to the doctor and more anxiety in comparison to heterosexual men who were not in a steady relationship. Additionally, immigration history appeared as a potential resiliency factor, such that gay men who were not born in Israel reported less frequent doctor visits and less anxiety in comparison to heterosexual men who were not born in Israel.

CONCLUSIONS: This study presents a pioneering examination of physical and mental health disparities in an Israeli sample of middle-aged and older gay and heterosexual men. These results may call the attention of clinicians and policymakers to both vulnerabilities and strengths of middle-aged and older gay men.}, } @article {pmid33743147, year = {2021}, author = {Kato, E and Mori, N and Mugikura, S and Sato, S and Ishida, T and Takase, K}, title = {Value of ultrafast and standard dynamic contrast-enhanced magnetic resonance imaging in the evaluation of the presence and extension of residual disease after neoadjuvant chemotherapy in breast cancer.}, journal = {Japanese journal of radiology}, volume = {39}, number = {8}, pages = {791-801}, pmid = {33743147}, issn = {1867-108X}, support = {18K07742//Japan Society for the Promotion of Science/ ; 19K17159//Japan Society for the Promotion of Science/ ; }, mesh = {*Breast Neoplasms/diagnostic imaging/drug therapy ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging ; *Neoadjuvant Therapy ; Neoplasm, Residual/diagnostic imaging ; Time Factors ; }, abstract = {PURPOSE: To evaluate the diagnostic performance of ultrafast and standard dynamic contrast-enhanced (DCE)-MRI in evaluating the residual disease after neoadjuvant chemotherapy (NAC) for breast cancer.

MATERIALS AND METHODS: Sixty-seven consecutive patients underwent MRI after NAC. Visual analysis of enhancement was performed on ultrafast and standard DCE-MRI, and compared between no residual disease and residual disease groups. The lesion diameters measured on the last phase of ultrafast DCE-MRI and early and delayed phases of standard DCE-MRI were compared with pathological diameter of entire residual cancer and residual invasive ductal carcinoma (IDC).

RESULTS: The visual analysis in the delayed phase of standard DCE-MRI exhibited the highest sensitivity (90%), whereas ultrafast DCE-MRI revealed the highest positive predictive value (92%). There were no significant differences between the diameters in the delayed phase of the standard DCE-MRI and the pathological entire residual cancer (p = 0.97), and the diameters in ultrafast DCE-MRI and the pathological residual IDC (p = 0.97).

CONCLUSION: The delayed phase of standard DCE-MRI may be effective for detecting the residual disease and evaluating the extension of entire residual cancer. Enhancement in ultrafast DCE-MRI may be strongly suggestive of the presence of residual disease, and effective for evaluating the extension of residual IDC.}, } @article {pmid33735776, year = {2021}, author = {Levin, Y and Lev Bar-Or, R and Forer, R and Vaserman, M and Kor, A and Lev-Ran, S}, title = {The association between type of trauma, level of exposure and addiction.}, journal = {Addictive behaviors}, volume = {118}, number = {}, pages = {106889}, doi = {10.1016/j.addbeh.2021.106889}, pmid = {33735776}, issn = {1873-6327}, mesh = {*Alcoholism ; *Behavior, Addictive/epidemiology ; Checklist ; Humans ; Risk Factors ; *Substance-Related Disorders/epidemiology ; }, abstract = {Exposure to trauma is considered a risk factor for the development of addictive disorders. Currently, there is a knowledge gap concerning specific links between types and levels of exposure to traumatic events and addiction.In this study we explored the associations between interpersonal trauma and risk of addictive behaviors, stratified by type of trauma (physical, weapon, sexual assault, and combat) and level of exposure (direct/indirect), focusing on a wide range of substances and behaviors. Data from an online representative sample of 4025 respondents were collected, including the Life Events Checklist (LEC-5), substance use disorders and behavioral addictions metrics, and sociodemographic data. Substantial differences were found between specific types of trauma and risk of addiction. Among those exposed to sexual assault, the risk of alcohol use disorder was found to 15.4%, 95%CI[14.4-16.4%], compared to 12.1%,95%CI[11.3-12.8] among those exposed to combat-related trauma. Both direct and indirect exposure to trauma were found to be significantly related with risk of addiction. While direct exposure was most highly associated with addictions across several types of trauma, in the case of combat-related trauma, indirect exposure was more highly associated with alcohol and pornography addiction (14.5%,95%CI[13.2-15.8%] and 10.0%, 95%CI[6.3-15.0%], respectively) compared to direct exposure (10.7%,95%CI[9.9-11.6%] and 7.4%, 95%CI[4.7-11.6%], respectively). Our findings emphasize the strong association between all types of trauma and the risk of several specific substance and behavioral addictions. Specifically, the role of indirect exposure to trauma is highlighted.}, } @article {pmid33735360, year = {2021}, author = {Yaman, ME and Kayili, HM and Albayrak, M and Kadioglu, Y and Salih, B}, title = {Differential N-glycosylation profiling of formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma tissues using MALDI-TOF-MS.}, journal = {Molecular omics}, volume = {17}, number = {3}, pages = {394-404}, doi = {10.1039/d0mo00150c}, pmid = {33735360}, issn = {2515-4184}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Case-Control Studies ; Female ; Glycosylation ; Humans ; Mannose/*chemistry ; Middle Aged ; N-Acetylneuraminic Acid/chemistry ; Paraffin Embedding ; Polysaccharides/*analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tissue Fixation ; ortho-Aminobenzoates/chemistry ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.}, } @article {pmid33731245, year = {2021}, author = {Ginzburg, K and Mikulincer, M and Ohry, A and Solomon, Z}, title = {Echoes from the past: adjustment of aging former prisoners of war to the COVID-19 pandemic.}, journal = {Psychological medicine}, volume = {}, number = {}, pages = {1-9}, pmid = {33731245}, issn = {1469-8978}, abstract = {BACKGROUND: The aim of this study was to examine whether exposure to previous traumatic events is a risk factor for stress reactions during this pandemic. Capitalizing on a 29-year longitudinal study of Israeli ex-prisoners of war (ex-POWs) and combat veterans, we examined whether captivity is a risk factor for fear of coronavirus disease 2019 (COVID-19) and COVID-19-induced acute stress disorder (COVID-19 ASD) beyond the effects of combat exposure and other stressful life events. In addition, we examined the contribution of captivity experiences (severity of captivity, experience of solitary confinement, and suffering during captivity) and veterans' appraisal of the impact of their war-related experiences on adjustment to the current quarantine and isolation to fear of COVID-19 and COVID-19 ASD.

METHODS: One-hundred-and-twenty Israeli ex-POWs from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) filled out self-report questionnaires 18 (T1), 35 (T2), 42 (T3), and 47 (T4) years after the war.

RESULTS: Findings revealed that although ex-POWs and controls did not differ in their level of exposure to COVID-19, ex-POWS reported higher levels of fear of COVID-19 and COVID-19 ASD than controls. Suffering during captivity, measured at 1991, and participants' appraisal of the extent to which their war-related experiences affected adjustment to COVID-19 were significantly associated with fear of COVID-19 and COVID-19 ASD.

CONCLUSIONS: The findings of the study demonstrate the long-term effects of exposure to traumatic experiences (captivity) during young adulthood on adjustment to an unrelated collective stress, such as COVID-19, 40 years later.}, } @article {pmid33730716, year = {2021}, author = {Bar-Or, RL and Kor, A and Jaljuli, I and Lev-Ran, S}, title = {The Epidemiology of Substance Use Disorders among the Adult Jewish Population in Israel.}, journal = {European addiction research}, volume = {27}, number = {5}, pages = {362-370}, doi = {10.1159/000513776}, pmid = {33730716}, issn = {1421-9891}, mesh = {Adult ; *Alcoholism ; Humans ; Israel/epidemiology ; Jews/statistics & numerical data ; Prevalence ; *Substance-Related Disorders/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.

METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.

RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).

CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.}, } @article {pmid33726715, year = {2021}, author = {Mallard, SR and Clifford, KA and Park, R and , and Cousins, K and Patton, A and Woodfield, JC and Thompson-Fawcett, M}, title = {Role for colorectal teams to support non-colorectal teams to improve clinical outcomes and adherence to ERAS guidelines for segmental colectomy: a cohort study.}, journal = {BMC surgery}, volume = {21}, number = {1}, pages = {132}, pmid = {33726715}, issn = {1471-2482}, mesh = {Cohort Studies ; *Colectomy ; Elective Surgical Procedures ; Enhanced Recovery After Surgery ; Guideline Adherence/statistics & numerical data ; Humans ; *Interprofessional Relations ; Length of Stay/statistics & numerical data ; New Zealand ; *Patient Care Team/organization & administration ; Practice Guidelines as Topic ; *Professional Role ; Treatment Outcome ; }, abstract = {BACKGROUND: To identify whether compliance with Enhanced Recovery After Surgery (ERAS) Society recommendations is associated with length of stay (LOS) in a New Zealand hospital for patients undergoing segmental colectomy in mixed acute and elective general surgery wards.

METHODS: Consecutive elective colorectal surgeries (n = 770) between October 2012 and February 2019 were audited. Patients with non-segmental colectomies, multi-organ surgeries, LOS > 14 days, and those who died were excluded. Logistic regression was used to determine the relationship between patient demographics, compliance with ERAS guidelines, and suboptimal LOS (> 4 days).

RESULTS: Analysis included 376 patients. Age, surgery prior to 2014, surgical approach, non-colorectal surgical team, operation type, and complications were significantly associated with suboptimal LOS. Non-compliance with ERAS recommendations for laparoscopy [OR 8.9, 95% CI (4.52, 19.67)], removal of indwelling catheters (IDC) [OR 3.14, 95% CI (1.85, 5.51)], use of abdominal drains [OR 4.27, 95% CI (0.99, 18.35)], and removal of PCA [OR 8.71, 95% CI (1.78, 157.27)], were associated with suboptimal LOS (univariable analysis). Multivariable analysis showed that age, surgical team, late removal of IDC, and open approach were independent predictors of suboptimal LOS.

CONCLUSIONS: Non-compliance with ERAS guidelines for laparoscopic approach and early removal of IDC was higher among procedures performed by non-colorectal surgery teams, and was also associated with adverse postoperative events and suboptimal LOS. This study demonstrates the importance of the surgical team's expertise in affecting surgical outcomes, and did not find significant independent associations between most individual ERAS guidelines and suboptimal LOS once adjusting for other factors.}, } @article {pmid33725931, year = {2021}, author = {Oh, BH and Woo, CG and Lee, YJ and Park, YS}, title = {Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.}, journal = {Medicine}, volume = {100}, number = {11}, pages = {e24373}, pmid = {33725931}, issn = {1536-5964}, support = {NRF-2019R1A2C1085809//Chungbuk National University Korea National University Development Project (2020)/ ; }, mesh = {Brain Neoplasms/metabolism/*secondary ; Breast Neoplasms, Male/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {RATIONALE: Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis.

PATIENT CONCERNS: we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen).

DIAGNOSES: Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -).

INTERVENTIONS: The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions).

OUTCOMES: There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care.

LESSONS: Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.}, } @article {pmid33723981, year = {2021}, author = {Parmeshwar, N and Alcon, A and Kim, EA}, title = {A Dual-Surgeon Approach to Breast Cancer Surgery in a Transmale.}, journal = {Annals of plastic surgery}, volume = {87}, number = {6}, pages = {633-638}, pmid = {33723981}, issn = {1536-3708}, mesh = {Adult ; *Breast Neoplasms/surgery ; Chemotherapy, Adjuvant ; Humans ; Male ; Mastectomy ; Nipples ; *Surgeons ; }, abstract = {With increasing numbers of gender-affirming chest surgery, new questions regarding breast cancer management and surgical practice arise. Guided by our case report, we present a comprehensive review of breast cancer surgery in a transman to educate both plastic and breast surgeons on various factors to consider when caring for these patients.Our case involves a 31-year-old transmale patient who presented for plastic surgery consultation for gender-affirming mastectomy but was subsequently found to have a right breast mass. This is the first case in the literature of a transmale on hormone therapy with breast cancer interested in gender-affirming surgery, thus requiring a dual-surgeon approach for oncologic and gender-affirming mastectomy. With a multidisciplinary patient-centered approach involving breast surgery, plastic surgery, medical oncology, and radiology, we devised a surgical plan to safely remove his breast tissue with consideration for his gender-affirming goals. He underwent a right skin-sparing mastectomy with sentinel node biopsy and left prophylactic skin-sparing mastectomy through skin markings by the plastic surgeon, with bilateral free nipple grafts. Final pathology confirmed estrogen and progesterone receptor-positive and androgen receptor-positive invasive ductal carcinoma with clear margins and negative sentinel node. The patient did not require adjuvant chemotherapy or radiation but was started on adjuvant hormone therapy targeting his hormone receptor positive cancer. He elected to stay on low-dose masculinizing hormone therapy with continued surveillance examinations.We follow our case with a review of the current literature involving breast cancer in transmales to explore current screening practices, surgical recommendations, adjuvant therapies, continuation of masculinizing hormone therapy, and postoperative surveillance guidelines in the hopes of informing plastic surgeons in having these discussions with their transmale patients and thus improving informed cancer care for this population.}, } @article {pmid33722650, year = {2021}, author = {Bartels, AK and Fadare, O and Hasteh, F and Zare, SY}, title = {Nonmass enhancement lesions of the breast on core needle biopsy: outcomes, frequency of malignancy, and pathologic findings.}, journal = {Human pathology}, volume = {111}, number = {}, pages = {92-97}, doi = {10.1016/j.humpath.2021.03.003}, pmid = {33722650}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology ; Carcinoma, Lobular/diagnosis/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; }, abstract = {Nonmass enhancement (NME) on breast magnetic resonance imaging (MRI) is defined as an area whose internal enhancement characteristics can be distinguished from the normal surrounding breast parenchyma, without an associated mass in the Breast Imaging Reporting and Data System lexicon. In this study, we evaluated the pathologic correlates of NME lesions of the breast identified on MRI at our institution, including the frequency of atypical or malignant lesions in the core needle biopsies (CNBs), performed after such a radiologic finding. A retrospective study was performed on all CNBs performed for NME on breast MRI between 2010 and 2019. A total of 443 biopsies from 411 patients were identified, comprising 5.5% of all CNBs over the study period. The pathologic diagnoses were benign in the majority of the biopsies (68.0%), whereas 11.5% and 20.5% of the cases were atypical and malignant lesions, respectively. Of the malignant cases, 69.2% were ductal carcinoma in situ (DCIS) and 30.8% were invasive carcinomas. The most common invasive cancer was invasive ductal carcinoma (50%), followed by invasive lobular carcinoma (39.3%). NME identified on breast MRI carried a significant (32%) risk of atypia and malignancy in our cohort, which confirms that biopsy evaluation of these lesions is warranted. DCIS was the most commonly identified malignancy. Notably, among invasive cancers, invasive lobular carcinoma was identified at a substantially higher frequency that would be expected for that histotype.}, } @article {pmid33710293, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity.}, journal = {JAMA network open}, volume = {4}, number = {3}, pages = {e211785}, pmid = {33710293}, issn = {2574-3805}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/*mortality/pathology ; Carcinoma, Ductal/chemistry/*drug therapy/*mortality/pathology ; Cause of Death ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Young Adult ; }, abstract = {IMPORTANCE: Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer.

OBJECTIVE: To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT.

This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020.

EXPOSURES: NET vs NACT for IDC with strong HR positivity and ERBB2 negativity.

MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments.

RESULTS: A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.}, } @article {pmid33708922, year = {2021}, author = {Qian, L and Lv, Z and Zhang, K and Wang, K and Zhu, Q and Zhou, S and Chang, C and Tian, J}, title = {Application of deep learning to predict underestimation in ductal carcinoma in situ of the breast with ultrasound.}, journal = {Annals of translational medicine}, volume = {9}, number = {4}, pages = {295}, pmid = {33708922}, issn = {2305-5839}, abstract = {BACKGROUND: To develop an ultrasound-based deep learning model to predict postoperative upgrading of pure ductal carcinoma in situ (DCIS) diagnosed by core needle biopsy (CNB) before surgery.

METHODS: Of the 360 patients with DCIS diagnosed by CNB and identified retrospectively, 180 had lesions upstaged to ductal carcinoma in situ with microinvasion (DCISM) or invasive ductal carcinoma (IDC) postoperatively. Ultrasound images obtained from the hospital database were divided into a training set (n=240) and validation set (n=120), with a ratio of 2:1 in chronological order. Four deep learning models, based on the ResNet and VggNet structures, were established to classify the ultrasound images into postoperative upgrade and pure DCIS. We obtained the area under the receiver operating characteristic curve (AUROC), specificity, sensitivity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) to estimate the performance of the predictive models. The robustness of the models was evaluated by a 3-fold cross-validation.

RESULTS: Clinical features were not significantly different between the training set and the test set (P value >0.05). The area under the receiver operating characteristic curve of our models ranged from 0.724 to 0.804. The sensitivity, specificity, and accuracy of the optimal model were 0.733, 0.750, and 0.742, respectively. The three-fold cross-validation results showed that the model was very robust.

CONCLUSIONS: The ultrasound-based deep learning prediction model is effective in predicting DCIS that will be upgraded postoperatively.}, } @article {pmid33708771, year = {2021}, author = {Mastrototaro, G and Zaghi, M and Massimino, L and Moneta, M and Mohammadi, N and Banfi, F and Bellini, E and Indrigo, M and Fagnocchi, G and Bagliani, A and Taverna, S and Rohm, M and Herzig, S and Sessa, A}, title = {TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {641410}, pmid = {33708771}, issn = {2296-634X}, abstract = {TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein is involved in the modulation of important cellular pathways and master regulators of transcriptional output, including nuclear receptor repressors, Wnt signaling, and MECP2 protein. However, TBL1XR1 mutations (including complete loss of its functions) have not been experimentally studied in a neurological context, leaving a knowledge gap in the mechanisms at the basis of the diseases. Here, we show that Tbl1xr1 knock-out mice exhibit behavioral and neuronal abnormalities. Either the absence of TBL1XR1 or its point mutations interfering with stability/regulation of NCOR complex induced decreased proliferation and increased differentiation in neural progenitors. We suggest that this developmental unbalance is due to a failure in the regulation of the MAPK cascade. Taken together, our results broaden the molecular and functional aftermath of TBL1XR1 deficiency associated with human disorders.}, } @article {pmid33708094, year = {2021}, author = {Tajima, Y and Sone, Y and Yaguchi, H and Mito, Y}, title = {Very-Late-Onset Neuromyelitis Optica Spectrum Disorder in a Patient with Breast Cancer and Parkinson Disease.}, journal = {Case reports in neurology}, volume = {13}, number = {1}, pages = {53-58}, pmid = {33708094}, issn = {1662-680X}, abstract = {Anti-aquaporin-4 (anti-AQP-4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder resulting in severe, recurrent optic neuritis, transverse myelitis, brain stem syndrome, and other types of neurological involvement. Its median age of onset has been reported to be around 40 years. We report herein a case of very-late-onset NMOSD (76 years of age) and try to promote its awareness as a type of neurological deterioration in elder patients. A 76-year-old woman suffering from Parkinson disease was admitted to our hospital because of consciousness disturbance. Cranial magnetic resonance imaging revealed the presence of fluid-attenuated inversion recovery high-signal-intensity lesions in the right peri- and intralateral ventricle. Part of this lesion and the meninges showed gadolinium enhancement. Physical examination revealed the presence of a tumor in the right breast, which was later diagnosed as invasive ductal carcinoma. In addition, laboratory examinations led to the detection of anti-AQP-4 antibodies in her serum; consequently, the patient was diagnosed as having NMOSD. She received initial pulsed steroid therapy, followed by right mastectomy. Although the patient's consciousness improved significantly, she developed abrupt-onset bilateral leg weakness and multiple longitudinal spinal cord lesions. Additional steroid therapy ameliorated the patient's leg weakness and reduced the swelling of the spinal cord.}, } @article {pmid33706600, year = {2021}, author = {Grant, M and de Graaf, E and Teunissen, S}, title = {A systematic review of classifications systems to determine complexity of patient care needs in palliative care.}, journal = {Palliative medicine}, volume = {35}, number = {4}, pages = {636-650}, pmid = {33706600}, issn = {1477-030X}, mesh = {Delivery of Health Care ; *Hospice and Palliative Care Nursing ; Humans ; *Palliative Care ; Patient Care Team ; Quality of Health Care ; }, abstract = {BACKGROUND: Providing the right care for each individual patient is a key element of quality palliative care. Complexity is a relatively new concept, defined as the nature of patients' situations and the extent of resulting needs. Classifying patients according to the complexity of their care needs can guide integration of services, anticipatory discussions, health service planning, resource management and determination of needs for specialist or general palliative care. However, there is no consistent approach to interpreting and classifying complexity of patient needs.

AIM: The aim of this article is to identify and describe classification systems for complexity of patient care needs in palliative care.

DESIGN: Narrative systematic review (PROSPERO registration number CRD42020182102).

DATA SOURCES: MEDLINE, Embase, CINAHL and PsychINFO databases were searched without time limitations. Articles were included that described classification systems for complexity of care requirements in populations with palliative care needs.

RESULTS: In total, 4301 records were screened, with nine articles identified reporting the use of patient classification systems in populations with palliative care needs. These articles included the use of six classification systems: HexCom, Perroca Scale, AN-SNAP, Hui Major Criteria, IDC-Pal and PALCOM. These systems were heterogenous in the manner they determined complexity of care needs. The HexCom and IDC-Pal systems contained items that covered all domains of complexity as described by Hodiamont; personal, social support, health care team and environment.

CONCLUSION: Although six classification systems have been developed, they access differing aspects of care needs and their application has been limited. The HexCOM and IDC-Pal systems offer the broadest determinations of complexity from an individual perspective. Further research is needed to apply these systems to populations external to those in which they were developed, and to appreciate how they may integrate with, and impact, clinical care.}, } @article {pmid33705172, year = {2021}, author = {Nachoum, R and Moed, A and Madjar, N and Kanat-Maymon, Y}, title = {Prenatal childbearing motivations, parenting styles, and child adjustment: A longitudinal study.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {35}, number = {6}, pages = {715-724}, doi = {10.1037/fam0000826}, pmid = {33705172}, issn = {1939-1293}, mesh = {Child ; Child Behavior ; Female ; Humans ; Infant, Newborn ; Longitudinal Studies ; Mothers ; *Motivation ; Parenting ; Pregnancy ; *Premature Birth ; }, abstract = {To have a child is among individuals' most important and meaningful decisions, with far-reaching implications. Despite evidence linking this decision to a wide variety of consequences, little is known about what motivates people to have children, and even less so about the long-term effects of different childbearing motivations on parenting and child adjustment. This study took a self-determination theory (SDT) perspective, examining how prenatal maternal autonomous and controlled childbearing motivations are related to child behavior problems through parenting styles. The rationale was that prenatal autonomous (sense of volition and self-fulfillment) and controlled (feeling pressured) childbearing motivations would shape later parental styles (autonomy-supportive vs. controlling, respectively) and, consequently, child adjustment. Over a period of 2 years beginning at pregnancy, 326 Israeli mothers reported their prenatal childbearing motivations, as well as parental styles and child behavior problems 20 months postpartum. Results of a path analysis revealed that prenatal autonomous childbearing motivation predicted autonomy-supportive parenting, yet the latter was not associated with children's behavior problems. Prenatal controlled motivation predicted controlling parenting, which, in turn, predicted children's internalizing and externalizing problems. No direct effects of childbearing motivation on children's behavior problems are observed, suggesting that childbearing motivation is a distal antecedent operating through more proximal factors such as parenting style. Findings were robust to children's temperamental tendencies and sociodemographic risk factors such as maternal age, high-risk pregnancy, and preterm birth. These findings have theoretical and practical implications for the discourse on motivations underlying the childbearing decision and their effects on parenting and child adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid33704190, year = {2020}, author = {Bondy, S and Tajzler, C and Hotte, SJ and Kapoor, A and Zbuk, K and Lalani, AA}, title = {Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report.}, journal = {Current oncology (Toronto, Ont.)}, volume = {28}, number = {1}, pages = {226-232}, pmid = {33704190}, issn = {1718-7729}, mesh = {*Adrenal Cortex Neoplasms/genetics ; *Adrenocortical Carcinoma/diagnosis/genetics ; Adult ; *Breast Neoplasms ; Female ; Genomics ; Humans ; *Li-Fraumeni Syndrome/genetics ; Mastectomy ; Neoplasm Recurrence, Local ; }, abstract = {Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina[®] HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.}, } @article {pmid33692758, year = {2021}, author = {Togashi, K and Nishitsuka, K and Hayashi, S and Namba, H and Goto, S and Takeda, Y and Suzuki, S and Kato, T and Yamada, Y and Konno, E and Yoshioka, T and Yamakawa, M and Sonoda, Y and Suzuki, T and Yamashita, H}, title = {Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {625663}, pmid = {33692758}, issn = {1664-2392}, mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*secondary ; Exophthalmos/diagnostic imaging/*etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Orbital Neoplasms/complications/diagnostic imaging/*secondary ; }, abstract = {BACKGROUND: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function.

CASE PRESENTATION: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation.

CONCLUSION: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.}, } @article {pmid33692294, year = {2021}, author = {Iwamoto, M and Takei, H and Ninomiya, J and Asakawa, H and Kurita, T and Yanagihara, K and Iida, S and Sakatani, T and Ohashi, R}, title = {Neoadjuvant Endocrine Therapy for Operable Breast Cancer: A Retrospective Analysis of Real-World Use.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {88}, number = {5}, pages = {448-460}, doi = {10.1272/jnms.JNMS.2021_88-603}, pmid = {33692294}, issn = {1347-3409}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Carcinoma, Lobular/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; *Neoadjuvant Therapy ; Prognosis ; Receptor, ErbB-2/metabolism/therapeutic use ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism/therapeutic use ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing the role of NET in breast cancer care.

METHODS: In a consecutive series of women with operable breast cancer who received NET for ≥28 days, associations of NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survival with clinicopathological factors were examined.

RESULTS: NET objectives were reduction in surgical extent in 49 patients, avoidance of surgery in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1,923), 869.8 (range, 36-4,859), and 55.8 (range, 39-113) days, respectively, in these cohorts (success rate: 79.6%, 64.5%, and 100%, respectively), and the differences were significant. Among patients in the former two cohorts, progression-free survival was significantly better in patients with stage 0 or I disease, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgical extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly associated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high preoperative endocrine prognostic index at the time of surgery after NET. Better recurrence-free survival after surgery was significantly associated with high ER expression after NET or high progesterone receptor expression before or after NET.

CONCLUSIONS: NET can help reduce surgical extent or avoid surgery in women with early breast cancer, ductal carcinoma, or high ER expression. NET may also aid in decisions related to postoperative systemic therapy to improve survival.}, } @article {pmid33691002, year = {2021}, author = {Greenbaum, D}, title = {Making Compassionate Use More Useful: Using real-world data, real-world evidence and digital twins to supplement or supplant randomized controlled trials.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {26}, number = {}, pages = {38-49}, pmid = {33691002}, issn = {2335-6936}, mesh = {*Compassionate Use Trials ; Computational Biology ; Humans ; *Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; United States ; United States Food and Drug Administration ; }, abstract = {The coronavirus pandemic has placed renewed focus on expanded access (EA) programs to provide compassionate use exceptions to the waves of patients seeking medical care in treating the novel disease. While commendable, justifiable, and compassionate, EA programs are not designed to collect the necessary vital clinical data that can be later used in the New Drug Application process before the U.S. Food and Drug Administration (FDA). In particular, they lack the necessary rigor of properly crafted and controlled randomized controlled trials (RCT) which ensure that each patient closely monitored for side effects and other potential dangers associated with the drug, that the data is documented, stable and are traceable and that the patient population is well defined with the defined target condition. Overall, while RCTs is deemed to be of the most reliable methodologies within evidence-based medicine, morally, however, they are problematic in EA programs. Nevertheless, actionable data ought to be collected from EA patients. To this end, we look to the growing incorporation of real-world data real-world evidence as increasingly useful substitutes for data collected via RCTs, including the ethical, legal and social implications thereof. Finally, we suggest the use of digital twins as an additional method to derive causal inferences from real-world trials involving expanded access patients.}, } @article {pmid33680266, year = {2021}, author = {Parikh, P and Rose, T and Jeong, D and Lam, CA and Afiat, TP and Rosa, M and Araujo, C}, title = {Diffuse intrasinusoidal hepatic metastasis from breast cancer: Multimodality imaging with pathology correlation.}, journal = {Radiology case reports}, volume = {16}, number = {5}, pages = {1005-1009}, pmid = {33680266}, issn = {1930-0433}, abstract = {Metastatic disease to the liver is a known and common site of breast cancer spread, classically presenting as either hypovascular or hypervascular masses. Rarely, hepatic metastatic disease may have an atypical diffuse and intrasinusoidal pattern of involvement, which may be radiographically occult or extremely challenging to diagnose even with multiphase contrast enhanced techniques. We report a case of a 28-year-old female with stage III invasive ductal carcinoma of the breast, who recently discontinued treatment due to pregnancy, presenting with progressive signs and symptoms of rapidly decompensating liver failure due to sinusoidal obstruction. Multimodality imaging was performed without evidence for focal hepatic metastatic disease; however, intrahepatic vein (IVC) compression was noted. Hepatic sinusoidal tumor infiltration was confirmed by liver biopsy. After palliative chemotherapy the disease became less infiltrative and more conspicuous on imaging, revealing itself as hepatic metastases, with decreased compression of the intrahepatic IVC and resolution of signs and symptoms of sinusoidal obstruction syndrome.}, } @article {pmid33679568, year = {2021}, author = {Carone, N and Bos, HMW and Shenkman, G and Tasker, F}, title = {Editorial: LGBTQ Parents and Their Children During the Family Life Cycle.}, journal = {Frontiers in psychology}, volume = {12}, number = {}, pages = {643647}, pmid = {33679568}, issn = {1664-1078}, } @article {pmid33676449, year = {2021}, author = {Ji, L and Cheng, L and Zhu, X and Gao, Y and Fan, L and Wang, Z}, title = {Risk and prognostic factors of breast cancer with liver metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {238}, pmid = {33676449}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/secondary/therapy ; Chemoradiotherapy, Adjuvant/methods ; Datasets as Topic ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/*epidemiology/secondary/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/analysis/antagonists & inhibitors/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).

METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.

RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).

CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.}, } @article {pmid33672165, year = {2021}, author = {Irelli, A and Sirufo, MM and Quaglione, GR and De Pietro, F and Bassino, EM and D'Ugo, C and Ginaldi, L and De Martinis, M}, title = {Invasive Ductal Breast Cancer with Osteoclast-Like Giant Cells: A Case Report Based on the Gene Expression Profile for Changes in Management.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33672165}, issn = {2075-4426}, abstract = {We report the case of a 49-year-old woman diagnosed with a rare histotype of early breast cancer (BC), invasive ductal carcinoma with osteoclast-like giant cells (OGCs), from the perspective of gene profile analysis tests. The patient underwent a quadrantectomy of the right breast with removal of 2 cm neoplastic nodule and three ipsilateral sentinel lymph nodes. The Oncotype Dx gave a recurrence score (RS) of 23, and taking into account the patient's age, an RS of 23 corresponds to a chemotherapy benefit of 6.5%. After a multidisciplinary collegial discussion, and in consideration of the patient's age, the absence of comorbidity, the premenopausal state, the rare histotype and the Oncotype Dx report, the patient was offered adjuvant chemotherapy treatment followed by hormone therapy. This case may be an example of the utility of integrating gene expression profiling tests into clinical practice in the adjuvant treatment decision of a rare histotype BC. The Oncotype Dx test required to supplement the histological examination made us opt for the proposal of a combined treatment of adjuvant chemotherapy followed by adjuvant hormone therapy. It demonstrates the importance of considering molecular tests and, in particular, the Oncotype Dx, in estimating the risk of disease recovery at 10 years in order to identify patients who benefit from hormone therapy alone versus those who benefit from the addition of chemotherapy, all with a view toward patient-centered oncology. Here, we discuss the possible validity and limitations of the Oncotype Dx in a rare luminal A-like histotype with high infiltrate of stromal/inflammatory cells.}, } @article {pmid33670876, year = {2021}, author = {Rand, D and Ravid, O and Atrakchi, D and Israelov, H and Bresler, Y and Shemesh, C and Omesi, L and Liraz-Zaltsman, S and Gosselet, F and Maskrey, TS and Beeri, MS and Wipf, P and Cooper, I}, title = {Endothelial Iron Homeostasis Regulates Blood-Brain Barrier Integrity via the HIF2α-Ve-Cadherin Pathway.}, journal = {Pharmaceutics}, volume = {13}, number = {3}, pages = {}, pmid = {33670876}, issn = {1999-4923}, support = {11816372//Defense Threat Reduction Agency/ ; 3-13576//Nehemia Rubin Excellence in Biomedical Research - The TELEM Program supported by the Aaron Gutwirth Fund and by a Ministry of Science and Technology/ ; }, abstract = {The objective of this study was to investigate the molecular response to damage at the blood brain barrier (BBB) and to elucidate critical pathways that might lead to effective treatment in central nervous system (CNS) pathologies in which the BBB is compromised. We have used a human, stem-cell derived in-vitro BBB injury model to gain a better understanding of the mechanisms controlling BBB integrity. Chemical injury induced by exposure to an organophosphate resulted in rapid lipid peroxidation, initiating a ferroptosis-like process. Additionally, mitochondrial ROS formation (MRF) and increase in mitochondrial membrane permeability were induced, leading to apoptotic cell death. Yet, these processes did not directly result in damage to barrier functionality, since blocking them did not reverse the increased permeability. We found that the iron chelator, Desferal© significantly decreased MRF and apoptosis subsequent to barrier insult, while also rescuing barrier integrity by inhibiting the labile iron pool increase, inducing HIF2α expression and preventing the degradation of Ve-cadherin specifically on the endothelial cell surface. Moreover, the novel nitroxide JP4-039 significantly rescued both injury-induced endothelium cell toxicity and barrier functionality. Elucidating a regulatory pathway that maintains BBB integrity illuminates a potential therapeutic approach to protect the BBB degradation that is evident in many neurological diseases.}, } @article {pmid33668874, year = {2021}, author = {Abramczyk, H and Brozek-Pluska, B and Kopec, M and Surmacki, J and Błaszczyk, M and Radek, M}, title = {Redox Imbalance and Biochemical Changes in Cancer by Probing Redox-Sensitive Mitochondrial Cytochromes in Label-Free Visible Resonance Raman Imaging.}, journal = {Cancers}, volume = {13}, number = {5}, pages = {}, pmid = {33668874}, issn = {2072-6694}, support = {UMO-2019/33/B/ST4/01961//Narodowe Centrum Nauki/ ; }, abstract = {To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm[-1] as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.}, } @article {pmid33667646, year = {2021}, author = {He, B and Chen, J and Song, W and Bai, Y}, title = {miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.}, journal = {Genomics}, volume = {113}, number = {3}, pages = {1469-1481}, doi = {10.1016/j.ygeno.2020.12.044}, pmid = {33667646}, issn = {1089-8646}, mesh = {*Carcinoma, Ductal ; Cell Line, Tumor ; DNA Methylation ; Demethylation ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.

METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.

RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.

CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.}, } @article {pmid33667422, year = {2021}, author = {Schwartz, CJ and Boroujeni, AM and Khodadadi-Jamayran, A and Heguy, A and Snuderl, M and Jour, G and Cotzia, P and Darvishian, F}, title = {Molecular analysis of encapsulated papillary carcinoma of the breast with and without invasion.}, journal = {Human pathology}, volume = {111}, number = {}, pages = {67-74}, doi = {10.1016/j.humpath.2021.02.005}, pmid = {33667422}, issn = {1532-8392}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; }, abstract = {Encapsulated papillary carcinomas (EPCs) of the breast are a unique variant of papillary carcinoma confined to a cystic space with absent or attenuated myoepithelial cell layer. Although staged as an in situ lesion, it can be associated with invasive ductal carcinoma (IDC). We sought to compare the genomic characteristics of pure EPC and EPC with associated invasive carcinoma (EPCi) at the genomic level. All cases of EPCi harbored recurrent hotspot mutations in PIK3CA. PIK3CA, KMT2A, and CREBBP deleterious somatic events were found across both tumor groups, irrespective of invasion status. At the whole transcriptomic level, EPCi cases displayed remarkably similar mRNA profiles when compared to EPC. When EPCi cases were compared with their corresponding IDC, despite significant overlap, we identified differential gene expression in 39 genes with enrichment of multiple pathways including extracellular matrix regulation, cell adhesion, and collagen fibril organization. Despite morphologic, genotypic, and transcriptomic overlap between pure EPC and EPCi, the latter tumors are likely advanced lesions with PIK3CA activating mutations and enrichment of stromal-related genes implicated in the switch to IDC.}, } @article {pmid33665961, year = {2021}, author = {Hartleben, G and Schorpp, K and Kwon, Y and Betz, B and Tsokanos, FF and Dantes, Z and Schäfer, A and Rothenaigner, I and Monroy Kuhn, JM and Morigny, P and Mehr, L and Lin, S and Seitz, S and Tokarz, J and Artati, A and Adamsky, J and Plettenburg, O and Lutter, D and Irmler, M and Beckers, J and Reichert, M and Hadian, K and Zeigerer, A and Herzig, S and Berriel Diaz, M}, title = {Combination therapies induce cancer cell death through the integrated stress response and disturbed pyrimidine metabolism.}, journal = {EMBO molecular medicine}, volume = {13}, number = {4}, pages = {e12461}, pmid = {33665961}, issn = {1757-4684}, mesh = {*Antineoplastic Agents ; Cell Death ; Humans ; *Neoplasms ; Niclosamide ; Pyrimidines ; }, abstract = {By accentuating drug efficacy and impeding resistance mechanisms, combinatorial, multi-agent therapies have emerged as key approaches in the treatment of complex diseases, most notably cancer. Using high-throughput drug screens, we uncovered distinct metabolic vulnerabilities and thereby identified drug combinations synergistically causing a starvation-like lethal catabolic response in tumor cells from different cancer entities. Domperidone, a dopamine receptor antagonist, as well as several tricyclic antidepressants (TCAs), including imipramine, induced cancer cell death in combination with the mitochondrial uncoupler niclosamide ethanolamine (NEN) through activation of the integrated stress response pathway and the catabolic CLEAR network. Using transcriptome and metabolome analyses, we characterized a combinatorial response, mainly driven by the transcription factors CHOP and TFE3, which resulted in cell death through enhanced pyrimidine catabolism as well as reduced pyrimidine synthesis. Remarkably, the drug combinations sensitized human organoid cultures to the standard-of-care chemotherapy paclitaxel. Thus, our combinatorial approach could be clinically implemented into established treatment regimen, which would be further facilitated by the advantages of drug repurposing.}, } @article {pmid33664023, year = {2021}, author = {Varshney, B and Kumar, A and Deka, L and Aiyer, HM}, title = {Bilateral alveolar rhabdomyosarcoma of breast: a rare entity.}, journal = {BMJ case reports}, volume = {14}, number = {3}, pages = {}, pmid = {33664023}, issn = {1757-790X}, mesh = {Adolescent ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; *Rhabdomyosarcoma ; *Rhabdomyosarcoma, Alveolar/diagnostic imaging ; *Rhabdomyosarcoma, Embryonal ; *Soft Tissue Neoplasms ; }, abstract = {Sarcomas of breast constitute less than 1% of all malignant breast tumours. Alveolar rhabdomyosarcoma (RMS) is very rare in breast with limited case reports in literature, and primary alveolar RMS arising from breast is still less common than metastatic RMS. Here, we report a case of primary bilateral alveolar RMS of breast in an adolescent female where the correct diagnosis was obfuscated by an overlap in the histological features of RMS and high-grade invasive ductal carcinoma.}, } @article {pmid33663447, year = {2021}, author = {Mills, MN and Walker, C and Thawani, C and Naz, A and Figura, NB and Kushchayev, S and Etame, A and Yu, HM and Robinson, TJ and Liu, J and Vogelbaum, MA and Forsyth, PA and Czerniecki, BJ and Soliman, HH and Han, HS and Ahmed, KA}, title = {Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {223}, pmid = {33663447}, issn = {1471-2407}, mesh = {Ado-Trastuzumab Emtansine/adverse effects/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Brain/pathology ; Brain Neoplasms/*secondary ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Necrosis ; *Radiosurgery/adverse effects ; Radiotherapy Dosage ; Receptor, ErbB-2/*analysis ; }, abstract = {BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation.

METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging.

RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis.

CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.}, } @article {pmid33662042, year = {2021}, author = {Mohamed, RI and Bargal, SA and Mekawy, AS and El-Shiekh, I and Tuncbag, N and Ahmed, AS and Badr, E and Elserafy, M}, title = {The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.}, journal = {PloS one}, volume = {16}, number = {3}, pages = {e0247837}, pmid = {33662042}, issn = {1932-6203}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; Precision Medicine ; Transcriptome ; Up-Regulation ; }, abstract = {In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients' response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients' samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients' samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients' samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.}, } @article {pmid33659906, year = {2021}, author = {Santamaría-García, H and Baez, S and Aponte-Canencio, DM and Pasciarello, GO and Donnelly-Kehoe, PA and Maggiotti, G and Matallana, D and Hesse, E and Neely, A and Zapata, JG and Chiong, W and Levy, J and Decety, J and Ibáñez, A}, title = {Uncovering social-contextual and individual mental health factors associated with violence via computational inference.}, journal = {Patterns (New York, N.Y.)}, volume = {2}, number = {2}, pages = {100176}, pmid = {33659906}, issn = {2666-3899}, abstract = {The identification of human violence determinants has sparked multiple questions from different academic fields. Innovative methodological assessments of the weight and interaction of multiple determinants are still required. Here, we examine multiple features potentially associated with confessed acts of violence in ex-members of illegal armed groups in Colombia (N = 26,349) through deep learning and feature-derived machine learning. We assessed 162 social-contextual and individual mental health potential predictors of historical data regarding consequentialist, appetitive, retaliative, and reactive domains of violence. Deep learning yields high accuracy using the full set of determinants. Progressive feature elimination revealed that contextual factors were more important than individual factors. Combined social network adversities, membership identification, and normalization of violence were among the more accurate social-contextual factors. To a lesser extent the best individual factors were personality traits (borderline, paranoid, and antisocial) and psychiatric symptoms. The results provide a population-based computational classification regarding historical assessments of violence in vulnerable populations.}, } @article {pmid33657249, year = {2021}, author = {Nakamura, R and Oyama, T and Inokuchi, M and Ishikawa, S and Hirata, M and Kawashima, H and Ikeda, H and Dobashi, Y and Ooi, A}, title = {Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration.}, journal = {Pathology international}, volume = {71}, number = {5}, pages = {326-336}, doi = {10.1111/pin.13087}, pmid = {33657249}, issn = {1440-1827}, support = {16K07165//JSPS KAKENHI/ ; 16K08687//JSPS KAKENHI/ ; 17K08727//JSPS KAKENHI/ ; 20K07378//JSPS KAKENHI/ ; //Smoking Research Foundation/ ; //The Hokkoku Cancer Foundation/ ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast/pathology ; *Breast Neoplasms/metabolism/pathology ; Cadherins/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Receptors, Cell Surface/*metabolism ; }, abstract = {Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.}, } @article {pmid33648758, year = {2021}, author = {He, X and Zhou, J and Ye, S and Cheng, Q and Miao, H and Xu, N and Li, J and Pan, Z and Cheng, J and Wang, M}, title = {Differences in tumour heterogeneity based on dynamic contrast-enhanced MRI between tumour and peritumoural stroma for predicting Ki-67 status of invasive ductal carcinoma.}, journal = {Clinical radiology}, volume = {76}, number = {6}, pages = {470.e13-470.e22}, doi = {10.1016/j.crad.2020.12.008}, pmid = {33648758}, issn = {1365-229X}, mesh = {Adult ; Aged ; Breast/diagnostic imaging/metabolism/pathology ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Contrast Media ; Female ; Humans ; Image Enhancement/*methods ; Ki-67 Antigen/*metabolism ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {AIM: To evaluate and compare the heterogeneity of intratumour and peritumour areas in the prediction of Ki-67 of invasive ductal carcinoma (IDC) and the predictive accuracy of different contrast frames based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

MATERIALS AND METHODS: This study included 88 patients with histologically confirmed IDC with 57 patients with high Ki-67 status and 31 patients with low Ki-67 status. All patients underwent DCE-MRI before surgery. A grey-level co-occurrence matrix (GLCM) was performed on slice-matched images from six frames by drawing the region of the interest (ROI) on the inner and outer regions of the tumours. The correlations between texture characteristics and Ki-67 status of lesions were analysed, using the Mann-Whitney test and receiver operating characteristic curve analysis.

RESULTS: In the high-Ki-67 group, the entropy was significantly higher than that of the low-Ki-67 group (p<0.001). The entropy obtained, based on the tumour boundary as a band-like area inside and outside at the first post-contrast series, revealed the highest receiver operating characteristic (AUC = 0.765). In the multivariate analysis, a higher entropy value (>4.305; p<0.001) remained independently associated with a high-Ki-67 status after adjustment for menopausal status, tumour size, histologic grade, oestrogen receptor (ER) status, and progesterone receptor (PR) status. The other parameters did not show significant differences between the high- and low-Ki-67 groups.

CONCLUSION: Heterogeneity analysis based on DCE-MRI could discriminate between high- and low-Ki-67 status. Texture characteristics from the band-like region inside and outside the tumour boundary could predict the Ki-67 status and showed higher accuracy.}, } @article {pmid33647708, year = {2021}, author = {Efrati, Y and Amichai-Hamburger, Y}, title = {Adolescents who solely engage in online sexual experiences are at higher risk for compulsive sexual behavior.}, journal = {Addictive behaviors}, volume = {118}, number = {}, pages = {106874}, doi = {10.1016/j.addbeh.2021.106874}, pmid = {33647708}, issn = {1873-6327}, mesh = {Adolescent ; *Adolescent Behavior ; Compulsive Behavior/epidemiology ; Female ; Humans ; Male ; Risk-Taking ; Sexual Behavior ; *Sexual Dysfunctions, Psychological ; }, abstract = {In addition to its expression offline, sexual behavior is frequently expressed online. Some adolescents solely engage in online sexual activities, whereas others in offline and online activities, or have no sexual experience at all. In the current research, we examined whether those who solely engage in online sexual activities are at greater risk for compulsive sexual behavior. In Study 1 (n = 164), we examined differences in compulsive sexual behavior (CSB) and risky sexual action tendencies between study groups. In Study 2 (n = 713), we statistically replicated the classification into different sexual behaviors and examined differences between the clusters in CSB, social tendencies and socio-demographic measures. Results indicated that adolescents who only engaged in online sexual activities had significantly higher percentage of clinical CSB, were less likely boys and more likely to be religious. There were not more prone to risky sexual behavior, however. The current research expands the knowledge about offline or online sexually related activities among adolescence.}, } @article {pmid33645934, year = {2021}, author = {Da Costa, I and Belnou, P and Soulier, A and Lapidus, N and Tsai, ES and Bourcier, E and Moisi, L and Sautet, A and Bonnet, F and Lescot, T and Verdonk, F}, title = {Impact of delayed patient flow on surgical outcomes after hip fracture: An observational study.}, journal = {European journal of anaesthesiology}, volume = {38 Suppl 1}, number = {}, pages = {S67-S68}, doi = {10.1097/EJA.0000000000001271}, pmid = {33645934}, issn = {1365-2346}, mesh = {Aged ; Aged, 80 and over ; Female ; France/epidemiology ; Hemorrhage/*epidemiology/etiology ; Hip Fractures/complications/*surgery ; Humans ; Male ; Middle Aged ; Outcome Assessment, Health Care ; Postoperative Complications/epidemiology ; Recovery of Function/*physiology ; Time Factors ; Time-to-Treatment/*statistics & numerical data ; Treatment Outcome ; }, } @article {pmid33645196, year = {2021}, author = {Gunizi, OC and Calis, H}, title = {A Collision Tumor with Squamous Cell Carcinoma of Skin Overlying Breast and Invasive Breast Carcinoma.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {31}, number = {2}, pages = {225-227}, doi = {10.29271/jcpsp.2021.02.225}, pmid = {33645196}, issn = {1681-7168}, mesh = {Breast ; *Breast Neoplasms ; *Carcinoma, Squamous Cell ; Female ; Humans ; *Neoplasms, Second Primary ; }, abstract = {Invasive breast cancer is the most common carcinoma in women. Invasive ductal carcinoma, not otherwise specified (NOS), is the largest group of invasive breast cancers. The second most common cancer of skin is squamous cell carcinoma (SCC). Collision tumor is a very rare and unusual tumor. It is defined as the concrescence of two distinct primary neoplasms at one site. Herein, we report a 56-year- female patient who had a collision tumor in the right breast, composed of moderately differentiated squamous cell carcinoma (SCC) and invasive breast carcinoma NOS. In the literature, collision tumors in the breast are very rare and reported in various combinations, but there is only one reported case with SCC and invasive breast cancer, the same as in our case. Key Words: Collision tumor, Squamous cell carcinoma, Invasive breast carcinoma.}, } @article {pmid33644087, year = {2020}, author = {Caffery, LJ and Rotemberg, V and Weber, J and Soyer, HP and Malvehy, J and Clunie, D}, title = {The Role of DICOM in Artificial Intelligence for Skin Disease.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {619787}, pmid = {33644087}, issn = {2296-858X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {There is optimism that artificial intelligence (AI) will result in positive clinical outcomes, which is driving research and investment in the use of AI for skin disease. At present, AI for skin disease is embedded in research and development and not practiced widely in clinical dermatology. Clinical dermatology is also undergoing a technological transformation in terms of the development and adoption of standards that optimizes the quality use of imaging. Digital Imaging and Communications in Medicine (DICOM) is the international standard for medical imaging. DICOM is a continually evolving standard. There is considerable effort being invested in developing dermatology-specific extensions to the DICOM standard. The ability to encode relevant metadata and afford interoperability with the digital health ecosystem (e.g., image repositories, electronic medical records) has driven the initial impetus in the adoption of DICOM for dermatology. DICOM has a dedicated working group whose role is to develop a mechanism to support AI workflows and encode AI artifacts. DICOM can improve AI workflows by encoding derived objects (e.g., secondary images, visual explainability maps, AI algorithm output) and the efficient curation of multi-institutional datasets for machine learning training, testing, and validation. This can be achieved using DICOM mechanisms such as standardized image formats and metadata, metadata-based image retrieval, and de-identification protocols. DICOM can address several important technological and workflow challenges for the implementation of AI. However, many other technological, ethical, regulatory, medicolegal, and workforce barriers will need to be addressed before DICOM and AI can be used effectively in dermatology.}, } @article {pmid33641217, year = {2021}, author = {Pramod, N and Nigam, A and Basree, M and Mawalkar, R and Mehra, S and Shinde, N and Tozbikian, G and Williams, N and Majumder, S and Ramaswamy, B}, title = {Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.}, journal = {The oncologist}, volume = {26}, number = {6}, pages = {e943-e953}, pmid = {33641217}, issn = {1549-490X}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular/genetics/therapy ; Female ; Humans ; Mastectomy, Segmental ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.}, } @article {pmid33640524, year = {2021}, author = {Bajpai, J and Simha, V and Shylasree, TS and Sarin, R and Pathak, R and Popat, P and Mokal, S and Dandekar, S and Bhansal, V and Ghosh, J and Nair, N and Gulia, S and Rath, S and Joshi, S and Wadasadawala, T and Sheth, T and Parmar, V and Banavali, SD and Badwe, RA and Gupta, S}, title = {Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.}, journal = {Breast (Edinburgh, Scotland)}, volume = {56}, number = {}, pages = {88-95}, pmid = {33640524}, issn = {1532-3080}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/epidemiology/pathology/therapy ; Female ; Gestational Age ; Humans ; Incidence ; India/epidemiology ; Mastectomy ; Postpartum Period ; Pregnancy ; *Pregnancy Complications, Neoplastic/epidemiology/pathology/therapy ; Prognosis ; Receptor, ErbB-2 ; Registries ; Survival Analysis ; }, abstract = {BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration.

METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC.

RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones.

CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.}, } @article {pmid33636408, year = {2021}, author = {Salita, A and Rosado, M and Mack, K and Pui, J and Zekman, R and Dinnan, K}, title = {Metastatic lobular carcinoma of the breast found incidentally on pathology following cholecystectomy for chronic cholecystitis: A case report.}, journal = {International journal of surgery case reports}, volume = {80}, number = {}, pages = {105612}, pmid = {33636408}, issn = {2210-2612}, abstract = {BACKGROUND: Traditional oncologic pattern of spread of breast cancer is metastasis to axillary lymph nodes, lung, liver and bone (Doval et al., 2006 [1]). Here we present a case of unknown synchronous breast cancer in a patient that was revealed on histopathologic assessment following elective cholecystectomy.

CASE SUMMARY: A 57 year old female presented for an elective laparoscopic cholecystectomy secondary to biliary colic. Histopathologic assessment of the gallbladder revealed metastatic adenocarcinoma with signet ring features, consistent with metastatic lobular carcinoma. The patient went on to have a complete oncologic workup that revealed invasive ductal carcinoma with components of high grade ductal carcinoma in situ in the left breast, lobular carcinoma in the right breast, and metastatic lobular carcinoma to left and right axillary lymph nodes as well as diffuse osseous metastatic disease.

CONCLUSIONS: Metastatic disease to the gallbladder found incidentally on elective cholecystectomy is a rare presentation of synchronous breast cancer.}, } @article {pmid33634508, year = {2021}, author = {Zhang, J and Lemberskiy, G and Moy, L and Fieremans, E and Novikov, DS and Kim, SG}, title = {Measurement of cellular-interstitial water exchange time in tumors based on diffusion-time-dependent diffusional kurtosis imaging.}, journal = {NMR in biomedicine}, volume = {34}, number = {6}, pages = {e4496}, pmid = {33634508}, issn = {1099-1492}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; R01 CA219964/CA/NCI NIH HHS/United States ; UH3 CA228699/CA/NCI NIH HHS/United States ; S10 OD018337/OD/NIH HHS/United States ; UG3 CA228699/CA/NCI NIH HHS/United States ; R01 CA160620/CA/NCI NIH HHS/United States ; P41 EB017183/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Brain Neoplasms/diagnostic imaging/pathology ; Breast Neoplasms ; *Diffusion Tensor Imaging ; Disease Models, Animal ; Female ; Glioma/diagnostic imaging/pathology ; Humans ; Mammary Neoplasms, Animal/diagnostic imaging/pathology ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms/*diagnostic imaging/pathology ; Water/*chemistry ; }, abstract = {PURPOSE: To assess the feasibility of using diffusion-time-dependent diffusional kurtosis imaging (tDKI) to measure cellular-interstitial water exchange time (τex) in tumors, both in animals and in humans.

METHODS: Preclinical tDKI studies at 7 T were performed with the GL261 glioma model and the 4T1 mammary tumor model injected into the mouse brain. Clinical studies were performed at 3 T with women who had biopsy-proven invasive ductal carcinoma. tDKI measurement was conducted using a diffusion-weighted STEAM pulse sequence with multiple diffusion times (20-800 ms) at a fixed echo time, while keeping the b-values the same (0-3000 s/mm[2]) by adjusting the diffusion gradient strength. The tDKI data at each diffusion time t were used for a weighted linear least-squares fit method to estimate the diffusion-time-dependent diffusivity, D(t), and diffusional kurtosis, K(t).

RESULTS: Both preclinical and clinical studies showed that, when diffusion time t ≥ 200 ms, D(t) did not have a noticeable change while K(t) decreased monotonically with increasing diffusion time in tumors and t ≥ 100 ms for the cortical ribbon of the mouse brain. The estimated τex averaged median and interquartile range (IQR) of GL261 and 4T1 tumors were 93 (IQR = 89) ms and 68 (78) ms, respectively. For the cortical ribbon, the estimated τex averaged median and IQR were 41 (34) ms for C57BL/6 and 30 (17) ms for BALB/c. For invasive ductal carcinoma, the estimated τex median and IQR of the two breast cancers were 70 (94) and 106 (92) ms.

CONCLUSION: The results of this proof-of-concept study substantiate the feasibility of using tDKI to measure cellular-interstitial water exchange time without using an exogenous contrast agent.}, } @article {pmid33629753, year = {2021}, author = {Min, X and Zhu, J and Shang, M and Liu, J and Zhang, K and Guo, L and Li, L and Cheng, L and Li, J}, title = {Stiffness Could be a Predictor of AJCC Prognostic Stage Groups in Preoperative Invasive Ductal Carcinoma.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {40}, number = {12}, pages = {2665-2674}, doi = {10.1002/jum.15657}, pmid = {33629753}, issn = {1550-9613}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal ; *Elasticity Imaging Techniques ; Female ; Humans ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {OBJECTIVES: This study aimed to evaluate the stiffness of 2-dimensional (2D) shear wave elastography (SWE) in preoperatively predicting the prognostic stage groups of invasive ductal carcinoma (IDC).

METHODS: Eighty-six newly diagnosed lesions on 83 patients with IDCs were analyzed. All parameters from conventional ultrasound and stiffness to virtual touch tissue imaging and quantification were collected, and mean shear wave velocity (SWVmean) was calculated. Data on maximum diameter, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), histologic grading system and Tumor Node Metastasis (TNM) stages were collected. The levels of maximum shear wave velocity (SWVmax), minimum shear wave velocity (SWVmin) and SWVmean were compared. In receiver operating characteristic (ROC) curves analysis, the diagnostic efficacy was found in area under the curve (AUC). Parallel mode was used to improve the predictive value of sensitivity.

RESULTS: The median stiffness of SWVmax and SWVmean for IDCs were 9.38 and 6.32 m/s for late stage (stages II, III, IV) and 6.39 m/s and 4.72 m/s for early stage (stage I) of the prognostic stage groups, respectively. The median stiffness values in the late stage were significantly higher than those in the early stage (P = .003, P = .005). The optimal cutoff stiffness of SWVmax and SWVmean were 8.62 and 6.13 m/s, respectively. In ROC curves analysis, the AUC for SWVmax was 0.742, and it showed a better diagnostic value than SWVmean (0.725). In predictive diagnosis, the sensitivity for SWVmax and SWVmean were both 62.50%. The parallel mode improved the prediction power of sensitivity to 68.75%.

CONCLUSIONS: Preoperative SWV level may serve as a promising prognostic imaging indicator for breast IDCs.}, } @article {pmid33629743, year = {2021}, author = {Santos, CS and Rodrigues, E and Ferreira, S and Moniz, T and Leite, A and Carvalho, SMP and Vasconcelos, MW and Rangel, M}, title = {Foliar application of 3-hydroxy-4-pyridinone Fe-chelate [Fe(mpp)3 ] induces responses at the root level amending iron deficiency chlorosis in soybean.}, journal = {Physiologia plantarum}, volume = {173}, number = {1}, pages = {235-245}, doi = {10.1111/ppl.13367}, pmid = {33629743}, issn = {1399-3054}, support = {PTDC/AGRPRO/3515/2014//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {*Anemia, Hypochromic ; Iron ; Plant Roots ; Pyridones ; *Soybeans ; }, abstract = {Iron (Fe) deficiency chlorosis (IDC) affects the growth of several crops, especially when growing in alkaline soils. The application of synthetic Fe-chelates is one of the most commonly used strategies in IDC amendment, despite their associated negative environmental impacts. In a previous work, the Fe-chelate tris(3-hydroxy-1-(H)-2-methyl-4-pyridinonate) iron(III) [Fe(mpp)3 ] has shown great potential for alleviating IDC in soybean (Glycine max) in the early stages of plant development under hydroponic conditions. Herein, its efficacy was verified under soil conditions in soybean grown from seed to full maturity. Chlorophyll levels, plant growth, root and shoot mineral accumulation (K, Mg, Ca, Na, P, Mn, Zn, Ni, and Co) and FERRITIN expression were accessed at V5 phenological stage. Compared to a commonly used Fe chelate, FeEDDHA, supplementation with [Fe(mpp)3 ] led to a 29% higher relative chlorophyll content, 32% higher root biomass, 36% higher trifoliate Fe concentration, and a twofold increase in leaf FERRITIN gene expression. [Fe(mpp)3 ] supplementation also resulted in increased accumulation of P, K, Zn, and Co. At full maturity, the remaining plants were harvested and [Fe(mpp)3 ] application led to a 32% seed yield increase when compared to FeEDDHA. This is the first report on the use of [Fe(mpp)3 ] under alkaline soil conditions for IDC correction, and we show that its foliar application has a longer-lasting effect than FeEDDHA, induces efficient root responses, and promotes the uptake of other nutrients.}, } @article {pmid33628571, year = {2021}, author = {Sarawagi, A and Maxwell, J}, title = {Chyle Leak after Right Axillary Lymph Node Dissection in a Patient with Breast Cancer.}, journal = {Case reports in surgery}, volume = {2021}, number = {}, pages = {8812315}, pmid = {33628571}, issn = {2090-6900}, abstract = {BACKGROUND: A female patient was diagnosed with a right-sided chyle leak following right skin sparing mastectomy, axillary lymph node dissection, and immediate tissue expander placement in the setting of invasive ductal carcinoma status post neoadjuvant chemotherapy. Summary. Our patient underwent a level I and II right axillary lymph node dissection followed by an axillary drain placement. On the first postoperative day, a change from serosanguinous to milky fluid in this drain was noted. The patient was diagnosed with a chyle leak based on the milky appearance and elevated triglyceride levels in the fluid. While chyle leaks are rare after an axillary dissection and even rarer to present on the right side, it is a complication of which breast surgeons should be aware. The cause of this complication is thought to be due to injury of the main thoracic duct, its branches, the subclavian duct, or its tributaries. Management is usually conservative; however, awareness of this potential complication even on the right side is of the utmost importance.

CONCLUSION: Chyle leaks are an uncommon complication of axillary node dissections and even rarer for them to present on the right side. It can be diagnosed by monitoring the drainage for changes in appearance and volume and by conducting supporting laboratory tests. Conservative management is generally suggested.}, } @article {pmid33627950, year = {2021}, author = {Rouillé, E and Bilbault, H and Levin, C and Lezmi, S}, title = {Characterization of an interdigitating dendritic cell hyperplasia case in a lymph node of a control C57BL/6 mouse.}, journal = {Journal of toxicologic pathology}, volume = {34}, number = {1}, pages = {101-106}, pmid = {33627950}, issn = {0914-9198}, abstract = {Interdigitating dendritic cell (IDC) hyperplasia is considered a benign spontaneous condition occasionally observed in the lymph nodes of mice. It has been rarely reported and, to the best of our knowledge, it has never been characterized using immunohistochemistry. The present work describes a spontaneous IDC hyperplasia case in a lymph node of a 16-week-old control female C57BL/6 mouse. Microscopically, the lymph node architecture was completely effaced by the proliferation of eosinophilic spindle cells with an abundant pale cytoplasm forming trabecule admixed lymphocyte infiltrates. The spindle cell population was positive for F4/80, partially positive for S100 calcium-binding protein A4 (S100A4), slightly positive for E-cadherin, and negative for α-Smooth muscle actin (SMA) and cytokeratin. Lymphocytes were positive for CD3, CD4, CD20 and negative for CD8. Spindle cells were considered to be originated from the myeloid lineage, based on the immunohistochemistry (IHC) results, but their precise origin remains unclear (IDC or macrophages); even if macrophage origin is most likely based on F4/80 positivity, this remains to be further clarified using other markers.}, } @article {pmid33627836, year = {2021}, author = {Morigny, P and Boucher, J and Arner, P and Langin, D}, title = {Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics.}, journal = {Nature reviews. Endocrinology}, volume = {17}, number = {5}, pages = {276-295}, pmid = {33627836}, issn = {1759-5037}, mesh = {Adipocytes, White/*metabolism ; Animals ; *Disease Management ; Homeostasis ; Humans ; Lipid Metabolism/*physiology ; Obesity/*metabolism/therapy ; }, abstract = {In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.}, } @article {pmid33626496, year = {2021}, author = {Lozano, R and Salles, DC and Sandhu, S and Aragón, IM and Thorne, H and López-Campos, F and Rubio-Briones, J and Gutierrez-Pecharroman, AM and Maldonado, L and di Domenico, T and Sanz, A and Prieto, JD and García, I and Pacheco, MI and Garcés, T and Llacer, C and Romero-Laorden, N and Zambrana, F and López-Casas, PP and Lorente, D and Mateo, J and Pritchard, CC and Antonarakis, ES and Olmos, D and Lotan, TL and Castro, E}, title = {Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {147}, number = {}, pages = {74-83}, doi = {10.1016/j.ejca.2021.01.027}, pmid = {33626496}, issn = {1879-0852}, support = {R01 CA185297/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA2 Protein/*genetics ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; DNA Mutational Analysis ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; *Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics ; Phenotype ; Prostatic Neoplasms/*genetics/pathology ; Risk Assessment ; Risk Factors ; Spain ; }, abstract = {BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour.

PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns.

RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3).

CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.}, } @article {pmid33625616, year = {2021}, author = {Chandrika, M and Chua, PJ and Muniasamy, U and Huang, RYJ and Thike, AA and Ng, CT and Tan, PH and Yip, GW and Bay, BH}, title = {Prognostic significance of phosphoglycerate dehydrogenase in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {186}, number = {3}, pages = {655-665}, pmid = {33625616}, issn = {1573-7217}, support = {NMRC/CIRG/1370/2013//National Medical Research Council/ ; }, mesh = {*Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; *Phosphoglycerate Dehydrogenase/genetics ; Prognosis ; Serine ; }, abstract = {PURPOSE: Breast cancer is the most common type of cancer affecting women worldwide. Phosphoglycerate dehydrogenase (PHGDH) is an oxidoreductase in the serine biosynthesis pathway. Although it has been reported to affect growth of various tumors, its role in breast cancer is largely unknown. This study aimed to analyze the expression of PHGDH in breast cancer tissue samples and to determine if PHGDH regulates breast cancer cell proliferation.

METHODS: Tissue microarrays consisting of 305 cases of breast invasive ductal carcinoma were used for immunohistochemical evaluation of PHGDH expression. The role of PHGDH in breast cancer was investigated in vitro by knocking down its expression and determining the effect on cell proliferation and cell cycling, and in ovo by using a chorioallantoic membrane (CAM) assay.

RESULTS: Immunohistochemical examination showed that PHGDH is mainly localized in the cytoplasm of breast cancer cells and significantly associated with higher cancer grade, larger tumor size, increased PCNA expression, and lymph node positivity. Analysis of the GOBO dataset of 737 patients demonstrated that increased PHGDH expression was associated with poorer overall survival. Knockdown of PHGDH expression in breast cancer cells in vitro resulted in a decrease in cell proliferation, reduction in cells entering the S phase of the cell cycle, and downregulation of various cell cycle regulatory genes. The volume of breast tumor in an in ovo CAM assay was found to be smaller when PHGDH was silenced.

CONCLUSION: The findings suggest that PHGDH has a regulatory role in breast cancer cell proliferation and may be a potential prognostic marker and therapeutic target in breast cancer.}, } @article {pmid33625070, year = {2021}, author = {Nakash, O and Nagar, M and Razon, L and Westen, D}, title = {Association Between Attachment Patterns and Personality Disorders: A Multimethod Multi-Informant Study Using a Clinical Sample.}, journal = {The Journal of nervous and mental disease}, volume = {209}, number = {5}, pages = {386-394}, doi = {10.1097/NMD.0000000000001310}, pmid = {33625070}, issn = {1539-736X}, mesh = {Adaptation, Psychological ; Adult ; Anxiety/psychology ; Comorbidity ; Female ; Humans ; Male ; *Object Attachment ; Outpatients/*statistics & numerical data ; Personality Disorders/*epidemiology ; Self Report ; }, abstract = {We investigated the association between personality disorders (PDs) and attachment patterns, and examined the construct validity of attachment patterns against adaptive functioning. We used a multimeasure multi-informant approach, which allowed us to disentangle the effects of the methods and to examine the utility of the various methods for measuring these constructs. The participants included 80 clinicians and 170 clinical outpatients, recruited via convenience sampling. Results showed that secure attachment was positively associated with adaptive functioning, whereas insecure patterns were negatively associated with adaptive functioning. Both categorical and dimensional PD diagnoses were associated with insecure attachment patterns. However, after controlling for comorbidity among the PD diagnoses, only some findings remained significant, most notably the association between borderline PD and the clinicians' assessment of preoccupied and incoherent/disorganized attachment, and the patients' self-reported attachment anxiety. Our findings underscore the importance of controlling for comorbidity in examining the associations between attachment patterns and PDs.}, } @article {pmid33621744, year = {2021}, author = {Gupta, V and Agarwal, P and Deshpande, P}, title = {Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer.}, journal = {Annals of diagnostic pathology}, volume = {52}, number = {}, pages = {151722}, doi = {10.1016/j.anndiagpath.2021.151722}, pmid = {33621744}, issn = {1532-8198}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology ; Carcinoma, Lobular/diagnosis/epidemiology/pathology ; Cross-Sectional Studies ; DNA Methylation ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; India/epidemiology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging/methods ; Phyllodes Tumor/diagnosis/epidemiology/pathology ; Prognosis ; Promoter Regions, Genetic/*genetics ; Tumor Suppressor Proteins/*genetics ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.

MATERIALS AND METHODS: A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.

RESULTS: Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.

CONCLUSION: A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.

MICRO ABSTRACT: The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.}, } @article {pmid33619822, year = {2021}, author = {Karakoc, S and Celik, S and Kaya, N and Bozkurt, O and Ellidokuz, H and Tuna, B and Yorukoglu, K and Mungan, MU}, title = {Prognostic value of intraductal carcinoma for adjuvant radiotherapy candidates after radical prostatectomy.}, journal = {International journal of clinical practice}, volume = {75}, number = {6}, pages = {e14099}, doi = {10.1111/ijcp.14099}, pmid = {33619822}, issn = {1742-1241}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/surgery ; Humans ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Prostate ; Prostate-Specific Antigen ; Prostatectomy ; *Prostatic Neoplasms/radiotherapy/surgery ; Radiotherapy, Adjuvant ; Retrospective Studies ; }, abstract = {OBJECTIVE: To investigate the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens and predictive value of IDC-P for biochemical recurrence and adjuvant therapy decision.

METHOD: We retrospectively evaluated patients who were performed RP between 2000 and 2014. Among, 67 patients who had stage pT3a tumour with negative surgical margin (Group 1, n = 35) and who had stage pT2 tumour with positive surgical margin (Group 2, n = 32) were included in the study. RP specimens were re-evaluated for the presence of IDC-P component and other prognostic factors. In both the groups, prognostic factors were compared according to the presence of IDC-P and biochemical recurrence status.

RESULTS: In Group 1, IDC-P was detected in five cases and biochemical recurrence was detected in three cases. Patients with IDC-P showed significantly higher biochemical recurrence than those without IDC-P (P = .002). In univariate analysis, IDC-P was found to be significantly associated with worse progression-free survival (P < .001). In Group 2, IDC-P was detected in four cases and biochemical recurrence was detected in 10 cases. Also, tumour volume was significantly higher in patients with IDC-P than those without IDC-P (P = .02). IDC-P was also significantly associated with worse progression-free survival in Group 2 (P = .033).

CONCLUSIONS: In both the groups, IDC-P was a prognostic factor for progression-free survival and/or biochemical recurrence. Especially in these patients, the presence of IDC-P might be helpful for postoperative adjuvant therapy management decision.}, } @article {pmid33616312, year = {2021}, author = {Kozma, KJ and Done, SJ and Egan, SE}, title = {The tumor cell-derived matrix of lobular breast cancer: a new vulnerability.}, journal = {EMBO molecular medicine}, volume = {13}, number = {3}, pages = {e13807}, pmid = {33616312}, issn = {1757-4684}, support = {//CIHR/Canada ; }, mesh = {Breast ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular ; Female ; Humans ; Retrospective Studies ; }, abstract = {Invasive lobular carcinoma (ILC) of the breast is a very common disease. Despite its prevalence, these tumors are relatively understudied. One reason for this is a relative lack of models for ILC. This challenge was addressed by Brisken and colleagues through development of an intraductal injection-based xenograft system for the study of ERα[+] breast cancers, including both ILC and more common invasive ductal carcinoma (IDC; Sflomos et al, 2016). In this issue of EMBO Molecular Medicine, the same group have applied intraductal injection-based xenografts to identify novel tumor cell-specific transcriptional signatures in ILC (Sflomos et al, 2021). In doing so they found overexpression of lysyl oxidase-like 1 (LOXL1) to be both responsible for the frequently seen stiff collagen-rich extracellular matrix of lobular breast cancer and essential for their robust growth and metastatic dissemination in vivo, thereby identifying a novel therapeutic target.}, } @article {pmid33614481, year = {2020}, author = {Zhang, M and Sadinski, M and Haddad, D and Bae, MS and Martinez, D and Morris, EA and Gibbs, P and Sutton, EJ}, title = {Background Parenchymal Enhancement on Breast MRI as a Prognostic Surrogate: Correlation With Breast Cancer Oncotype Dx Score.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {595820}, pmid = {33614481}, issn = {2234-943X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: Breast MRI background parenchymal enhancement (BPE) can potentially serve as a prognostic marker, by possible correlation with molecular subtype. Oncotype Dx, a gene assay, is a prognostic and predictive surrogate for tumor aggressiveness and treatment response. The purpose of this study was to investigate the association between contralateral non-tumor breast magnetic resonance imaging (MRI) background parenchymal enhancement and tumor oncotype score.

METHODS: In this retrospective study, patients with ER+ and HER2- early stage invasive ductal carcinoma who underwent preoperative breast MRI, oncotype risk scoring, and breast conservation surgery from 2008-2010 were identified. After registration, BPE from the pre and three post-contrast phases was automatically extracted using a k-means clustering algorithm. Four metrics were calculated: initial enhancement (IE) relative to the pre-contrast signal, late enhancement, overall enhancement (OE), and area under the enhancement curve (AUC). Histogram analysis was performed to determine first order metrics which were compared to oncotype risk score groups using Mann-Whitney tests and Spearman rank correlation analysis.

RESULTS: This study included 80 women (mean age = 51.1 ± 10.3 years); 46 women were categorized as low risk (≤17) and 34 women were categorized as intermediate/high risk (≥18) according to Oncotype Dx. For the mean of the top 10% pixels, significant differences were noted for IE (p = 0.032), OE (p = 0.049), and AUC (p = 0.044). Using the risk score as a continuous variable, correlation analysis revealed a weak but significant correlation with the mean of the top 10% pixels for IE (r = 0.26, p = 0.02), OE (r = 0.25, p = 0.02), and AUC (r = 0.27, p = 0.02).

CONCLUSION: BPE metrics of enhancement in the non-tumor breast are associated with tumor Oncotype Dx recurrence score, suggesting that the breast microenvironment may relate to likelihood of recurrence and magnitude of chemotherapy benefit.}, } @article {pmid33614164, year = {2020}, author = {Blum, K and Bowirrat, A and Baron, D and Lott, L and Ponce, JV and Brewer, R and Siwicki, D and Boyett, B and Gondre-Lewis, MC and Smith, DE and Panayotis K, T and Badgaiyan, S and Hauser, M and Fried, L and A, R and Downs, BW and Badgaiyan, RD}, title = {Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).}, journal = {Journal of systems and integrative neuroscience}, volume = {6}, number = {2}, pages = {}, pmid = {33614164}, issn = {2059-9781}, support = {R01 AA021262/AA/NIAAA NIH HHS/United States ; R01 NS073884/NS/NINDS NIH HHS/United States ; R21 MH073624/MH/NIMH NIH HHS/United States ; R41 MD012318/MD/NIMHD NIH HHS/United States ; }, abstract = {Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case -control studies indicating selective association of these risk alleles (measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data -a work in progress.}, } @article {pmid33613347, year = {2021}, author = {Eckstein, M and Zietlow, AL and Gerchen, MF and Levy, J}, title = {Editorial: Neurobiological Systems Underlying Reward and Emotions in Social Settings.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {644672}, pmid = {33613347}, issn = {1664-0640}, } @article {pmid33612000, year = {2021}, author = {Saguy, T and Reifen-Tagar, M and Joel, D}, title = {The gender-binary cycle: the perpetual relations between a biological-essentialist view of gender, gender ideology, and gender-labelling and sorting.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1822}, pages = {20200141}, pmid = {33612000}, issn = {1471-2970}, mesh = {Female ; *Gender Identity ; Humans ; Male ; *Politics ; Sex Factors ; *Social Perception ; }, abstract = {Gender inequality is one of the most pressing issues of our time. A core factor that feeds gender inequality is people's gender ideology-a set of beliefs about the proper order of society in terms of the roles women and men should fill. We argue that gender ideology is shaped, in large parts, by the way people make sense of gender differences. Specifically, people often think of gender differences as expressions of a predetermined biology, and of men and women as different 'kinds'. We describe work suggesting that thinking of gender differences in this biological-essentialist way perpetuates a non-egalitarian gender ideology. We then review research that refutes the hypothesis that men and women are different 'kinds' in terms of brain function, hormone levels and personality characteristics. Next, we describe how the organization of the environment in a gender-binary manner, together with cognitive processes of categorization drive a biological-essentialist view of gender differences. We then describe the self-perpetuating relations, which we term the gender-binary cycle, between a biological-essentialist view of gender differences, a non-egalitarian gender ideology and a binary organization of the environment along gender lines. Finally, we consider means of intervention at different points in this cycle. This article is part of the theme issue 'The political brain: neurocognitive and computational mechanisms'.}, } @article {pmid33611829, year = {2021}, author = {Huang, D and Zhou, B and Luo, ZZ and Yu, SC and Tang, B}, title = {Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th-17/Treg imbalance via the c-Jun/allograft inflammatory factor 1 axis.}, journal = {The Kaohsiung journal of medical sciences}, volume = {37}, number = {7}, pages = {594-603}, doi = {10.1002/kjm2.12367}, pmid = {33611829}, issn = {2410-8650}, support = {//The Science and Technology Plan of Jiangxi Province Health Committee, Grant/Award Number: 20204366/ ; //The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee, Grant/Award Number: 20181001/ ; 20204366//The Science and Technology Plan of Jiangxi Province Health Committee/ ; 20181001//The Science and Technology Plan of Jiangxi Provincial Health and Family Planning Committee/ ; }, mesh = {Allografts ; Animals ; Anthracenes/pharmacology ; CD4-Positive T-Lymphocytes/cytology ; Calcium-Binding Proteins/*metabolism ; Cell Differentiation ; Cells, Cultured ; DNA Methyltransferase 3A/*metabolism ; Dendritic Cells/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Microfilament Proteins/*metabolism ; Proto-Oncogene Proteins c-jun/*metabolism ; Pulmonary Disease, Chronic Obstructive/genetics ; Signal Transduction ; *Smoke ; Smoking/*adverse effects ; T-Lymphocytes, Regulatory/*metabolism ; Tetrazolium Salts/pharmacology ; Th17 Cells/metabolism ; Thiazoles/pharmacology ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder. Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4[+] T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.}, } @article {pmid33610628, year = {2021}, author = {McLamore, Q and Leidner, B and Park, J and Hirschberger, G and Li, M and Reinhard, D and Beals, K}, title = {Strong hearts, open minds: Cardiovascular challenge predicts non-defensive responses to ingroup-perpetrated violence.}, journal = {Biological psychology}, volume = {161}, number = {}, pages = {108054}, doi = {10.1016/j.biopsycho.2021.108054}, pmid = {33610628}, issn = {1873-6246}, mesh = {Australia ; Humans ; Iran ; *Motivation ; *Social Identification ; Violence ; }, abstract = {Reminders of ingroup-perpetrated violence represent a psychological stressor that some people respond to defensively (e.g., justifying the violence), while others react non-defensively (e.g., accepting collective responsibility). To explain these divergent responses, we applied the biopsychosocial model of challenge and threat to the context of intergroup conflict. Participants (N = 130) read about either an ingroup (American) or outgroup (Australian) soldier torturing an Iranian captive. We recorded cardiovascular responses while participants video-recorded introductions to an Iranian confederate who they believed they would meet. In the ingroup (but not the outgroup) condition, cardiovascular responses of challenge (relative to threat) were associated with less psychological defensiveness of ingroup-perpetrated violence and greater support for diplomacy towards its victims. Self-reported challenge/threat appraisals demonstrated no such relationships. These findings suggest that motivational states of challenge and threat can differentiate defensive and non-defensive responses, and that these motivational states may be better captured with physiological rather than self-report measures.}, } @article {pmid33608619, year = {2021}, author = {Wetstein, SC and Stathonikos, N and Pluim, JPW and Heng, YJ and Ter Hoeve, ND and Vreuls, CPH and van Diest, PJ and Veta, M}, title = {Deep learning-based grading of ductal carcinoma in situ in breast histopathology images.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {101}, number = {4}, pages = {525-533}, pmid = {33608619}, issn = {1530-0307}, mesh = {Biopsy ; Breast/pathology ; *Breast Neoplasms/diagnosis/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology ; *Deep Learning ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Grading/*methods ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed and evaluated a deep learning-based DCIS grading system. The system was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen's kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the three observers (o1, o2 and o3) (κo1,dl = 0.81, κo2,dl = 0.53 and κo3,dl = 0.40) than the observers amongst each other (κo1,o2 = 0.58, κo1,o3 = 0.50 and κo2,o3 = 0.42) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers (κo1,dl = 0.77, κo2,dl = 0.75 and κo3,dl = 0.70) as the observers amongst each other (κo1,o2 = 0.77, κo1,o3 = 0.75 and κo2,o3 = 0.72). The deep learning system better reflected the grading spectrum of DCIS than two of the observers. In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. To the best of our knowledge, this is the first automated system for the grading of DCIS that could assist pathologists by providing robust and reproducible second opinions on DCIS grade.}, } @article {pmid33608011, year = {2021}, author = {O'Donnell, AJ and Reece, SE}, title = {Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms.}, journal = {Malaria journal}, volume = {20}, number = {1}, pages = {105}, pmid = {33608011}, issn = {1475-2875}, support = {UF110155//The Royal Society/ ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; NF140517//The Royal Society/ ; RGP0046/2013//Human Frontier Science Program/ ; }, mesh = {Animals ; Anopheles/parasitology/*physiology ; *Circadian Rhythm ; Erythrocytes/parasitology ; Female ; Mosquito Vectors/parasitology/*physiology ; Plasmodium berghei/growth & development/*physiology ; *Reproduction, Asexual ; }, abstract = {BACKGROUND: Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious.

METHODS: This study reports a series of five experiments probing the relationships between the asynchronous IDC schedule of P. berghei and the rhythms of hosts and vectors by manipulating host time-of-day, photoperiod and feeding rhythms.

RESULTS: The results reveal that: (i) a lack coordination between host and parasite rhythms does not impose appreciable fitness costs on P. berghei; (ii) the IDC schedule of P. berghei is impervious to host rhythms, including altered photoperiod and host-feeding-related rhythms; (iii) there is weak evidence for daily rhythms in the density and activities of transmission stages; but (iv), these rhythms have little consequence for successful transmission to mosquitoes.

CONCLUSIONS: Overall, host rhythms do not affect the performance of P. berghei and its asynchronous IDC is resistant to the scheduling forces that underpin synchronous replication in closely related parasites. This suggests that natural variation in the IDC schedule across species represents different parasite strategies that maximize fitness. Thus, subtle differences in the ecological interactions between parasites and their hosts/vectors may select for the evolution of very different IDC schedules.}, } @article {pmid33608001, year = {2021}, author = {Nimmolrat, A and Sutham, K and Thinnukool, O}, title = {Patient triage system for supporting the operation of dispatch centres and rescue teams.}, journal = {BMC medical informatics and decision making}, volume = {21}, number = {1}, pages = {68}, pmid = {33608001}, issn = {1472-6947}, mesh = {*Emergency Medical Services ; Emergency Service, Hospital ; Humans ; Reproducibility of Results ; Retrospective Studies ; Thailand ; *Triage ; }, abstract = {BACKGROUND: The Thai medical application for patient triage, namely Triagist, is an mHealth application designed to support the pre-hospital process. However, since the functions of the application that are necessary for the pre-hospital process have been found not to be fully developed, the addition of a back-end system has been considered to increase its performance and usability.

OBJECTIVE: To determine the ability of the previous version to effectively manage the pre-hospital process and analyse the current problems with the pre-hospital operation. Therefore, the new system was developed to support the connection of dispatch centres or operational centres to the Triagist mobile application and system evaluation.

METHOD: Design thinking methodology was used to analyse, design and develop a patient triage system to support the pre-hospital process in Thailand based on users' requirements. 68 active members of the rescue teams and emergency medical staff in Chiang Mai and Lampang provinces were recruited to test the reliability of the system based on a prototype application.

RESULTS: The new medical mobile application for patient triage in Thailand was validated for use due to containing the two essential functions of Initial Dispatch Code (IDC) geolocation and IDC management. When the system was tested by emergency staff who were responsible for using it, those with the least experience were found to use it better than their highly experienced colleagues. Moreover, in cases where the system had been implemented, it was found to determine the frequency of symptoms, the time period during which cases occurred, and the density of cases in each area.

CONCLUSION: This system, which has been developed based on the use of smart technology, will play an important role in supporting emergency services in Thailand by enhancing the efficiency of the pre-hospital process. Emergency centres will receive IDC information from the geolocation system so that they can determine patients' location without undue delay. Emergency services will be able to rapidly prepare the necessary resources and administrative tasks will be supported by linking the dispatch centre to central rescue teams.}, } @article {pmid33605547, year = {2021}, author = {Xu, F and Gao, Y and Diao, X and Li, J and Jiang, H and Zhao, H}, title = {Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.}, journal = {Cancer medicine}, volume = {10}, number = {5}, pages = {1783-1790}, pmid = {33605547}, issn = {2045-7634}, mesh = {Adult ; Antigens, Tumor-Associated, Carbohydrate/*analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Breast/immunology/pathology ; Breast Neoplasms/complications/*immunology/pathology ; Carcinoma, Ductal, Breast/complications/*immunology/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*immunology/pathology ; Confidence Intervals ; Female ; Humans ; Hyperplasia/immunology/pathology ; Immunohistochemistry ; Logistic Models ; Nipple Discharge/*immunology ; Odds Ratio ; Papilloma, Intraductal/complications/*immunology/pathology ; Receptor, ErbB-2/analysis ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Mucin-associated sialyl-Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.

METHODS: PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.

RESULTS: PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2-positive IDC (p = 0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p = 0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p = 0.037) were statistically significant independent risk factors for malignant PND.

CONCLUSIONS: Mucin-associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.}, } @article {pmid33600720, year = {2021}, author = {Haberl, H and Wiedenhofer, D and Schug, F and Frantz, D and Virág, D and Plutzar, C and Gruhler, K and Lederer, J and Schiller, G and Fishman, T and Lanau, M and Gattringer, A and Kemper, T and Liu, G and Tanikawa, H and van der Linden, S and Hostert, P}, title = {High-Resolution Maps of Material Stocks in Buildings and Infrastructures in Austria and Germany.}, journal = {Environmental science & technology}, volume = {55}, number = {5}, pages = {3368-3379}, pmid = {33600720}, issn = {1520-5851}, mesh = {Austria ; Germany ; }, abstract = {The dynamics of societal material stocks such as buildings and infrastructures and their spatial patterns drive surging resource use and emissions. Two main types of data are currently used to map stocks, night-time lights (NTL) from Earth-observing (EO) satellites and cadastral information. We present an alternative approach for broad-scale material stock mapping based on freely available high-resolution EO imagery and OpenStreetMap data. Maps of built-up surface area, building height, and building types were derived from optical Sentinel-2 and radar Sentinel-1 satellite data to map patterns of material stocks for Austria and Germany. Using material intensity factors, we calculated the mass of different types of buildings and infrastructures, distinguishing eight types of materials, at 10 m spatial resolution. The total mass of buildings and infrastructures in 2018 amounted to ∼5 Gt in Austria and ∼38 Gt in Germany (AT: ∼540 t/cap, DE: ∼450 t/cap). Cross-checks with independent data sources at various scales suggested that the method may yield more complete results than other data sources but could not rule out possible overestimations. The method yields thematic differentiations not possible with NTL, avoids the use of costly cadastral data, and is suitable for mapping larger areas and tracing trends over time.}, } @article {pmid33599914, year = {2021}, author = {Tanaka, K and Masuda, N and Hayashi, N and Sagara, Y and Hara, F and Kadoya, T and Matsui, A and Miyazaki, C and Shien, T and Tokunaga, E and Hayashi, T and Niikura, N and Maeda, S and Komoike, Y and Bando, H and Kanbayashi, C and Iwata, H}, title = {Clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with ductal carcinoma in situ (DCIS): a multi-institutional retrospective cohort study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {28}, number = {4}, pages = {896-903}, pmid = {33599914}, issn = {1880-4233}, support = {26-A-4//the National Cancer Center Research and Development Fund/ ; 20ck0106429h0003//the Japan Agency for Medical Research and Development/ ; }, mesh = {Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology ; Female ; Humans ; Mammography/methods ; Middle Aged ; Postoperative Period ; Retrospective Studies ; }, abstract = {BACKGROUND: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS.

PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records.

RESULTS: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm.

CONCLUSION: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.}, } @article {pmid33598361, year = {2021}, author = {Miyazaki, Y and Tabata, N and Kubo, Y and Shinozaki, K}, title = {Utility of Tissue Classification in Invasive Ductal Carcinoma using Dynamic Magnetic Resonance Imaging of the Mammary Gland.}, journal = {Journal of clinical imaging science}, volume = {11}, number = {}, pages = {4}, pmid = {33598361}, issn = {2156-7514}, abstract = {OBJECTIVES: In Japan, invasive ductal carcinomas, which account for 75% of breast cancer cases, are sub-classified as solid, tubule-forming, scirrhous, and other types based on the histopathological findings. Although time-intensity curve (TIC) analysis of magnetic resonance (MR) images has shown diagnostic ability in differentiating benign and malignant tumors, its ability to diagnose different tumor tissue types has not yet been achieved. In this study, we report a histological classification of invasive ductal carcinoma using the TIC analysis of dynamic MR images of the mammary gland.

MATERIAL AND METHODS: A total of 312 invasive ductal carcinomas were analyzed, and each tissue type that indicated malignancy in the washout parts of the tumors was classified and characterized using the TIC.

RESULTS: The tissue was classified, and the results were then compared to the pathohistological diagnosis. Using this method, the accuracy of tissue classification by quantitative analysis of TIC-MR images was 86.9% (271/312), which was higher than that obtained by ultrasonography 68.9% (215/312).

CONCLUSION: This method is effective for classifying tissue types in invasive ductal carcinoma.}, } @article {pmid33597376, year = {2021}, author = {Mimata, A and Yoshitomi, S and Morikawa, N and Hara, K and Tsuji, H}, title = {[A Case of HER2-Positive Metastatic Breast Cancer Achieved a Complete Response to Paclitaxel and Trastuzumab in Combination with Pertuzumab in Fifth Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {48}, number = {2}, pages = {263-265}, pmid = {33597376}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; Mastectomy ; Paclitaxel/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {We report a case of HER2-positive metastatic breast cancer achieved a complete response(CR)to paclitaxel(PTX) and trastuzumab(HER) in combination with pertuzumab(PER) in 5th therapy. A 69-year-old woman was diagnosed left breast cancer and underwent mastectomy and sentinel lymph node biopsy in January 2011. Pathological examination revealed an invasive ductal carcinoma that was ER 0%, PgR 0%, HER2(3+), Ki-67 67% and node negative. Two years after the operation, she found multiple lung metastases in both lungs. She was administered drug treatment as HER2-positive metastatic breast cancer, but multiple lung metastases got worse after 4th treatment. Weekly PTX, trastuzumab and pertuzumab were administered as 5th therapy. After 2 months, lung metastases diminished significantly. After 44 courses of drug treatment, positron emission tomography computed tomography(PET-CT)scan revealed CR. She wanted to cease treatment, so she continues to get CT scan every half a year and the CR has been maintained.}, } @article {pmid33596950, year = {2021}, author = {Nayak, A and Saxena, H and Bathula, C and Kumar, T and Bhattacharjee, S and Sen, S and Gupta, A}, title = {Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum.}, journal = {Malaria journal}, volume = {20}, number = {1}, pages = {100}, pmid = {33596950}, issn = {1475-2875}, mesh = {Antimalarials/chemistry/*pharmacology ; Artemisinins/*pharmacology ; *Drug Resistance ; Indoles/chemistry/*pharmacology ; Plasmodium falciparum/*drug effects ; }, abstract = {BACKGROUND: Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

METHODS: The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library.

RESULTS: Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds.

CONCLUSION: Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.}, } @article {pmid33593316, year = {2021}, author = {Liu, J and Zheng, X and Han, Z and Lin, S and Han, H and Xu, C}, title = {Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {168}, pmid = {33593316}, issn = {1471-2407}, mesh = {Adenocarcinoma/*mortality/pathology/therapy ; Aged ; Breast Neoplasms/*mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program/*statistics & numerical data ; Survival Rate ; }, abstract = {BACKGROUND: The prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.

METHODS: We retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient's 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).

RESULTS: Comparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.

CONCLUSIONS: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.}, } @article {pmid33582923, year = {2021}, author = {Hu, XQ and Peng, L and Wintermark, M and Lipson, JA and Zhang, YR and Gao, Y}, title = {Shear Wave Elastography of Invasive Ductal Carcinoma: Correlations between Shear Wave Velocity and Histological Prognostic Factors.}, journal = {Current medical science}, volume = {41}, number = {1}, pages = {173-179}, pmid = {33582923}, issn = {2523-899X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal/classification/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/*methods/standards ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Sensitivity and Specificity ; }, abstract = {The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P<0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.}, } @article {pmid33582618, year = {2021}, author = {Durhan, G and Poker, A and Settarzade, E and Karakaya, J and Kösemehmetoğlu, K and Akpınar, MG and Demirkazık, FB}, title = {Magnetic resonance imaging findings of invasive breast cancer in different histological grades and different histopathological types.}, journal = {Clinical imaging}, volume = {76}, number = {}, pages = {98-103}, doi = {10.1016/j.clinimag.2021.01.039}, pmid = {33582618}, issn = {1873-4499}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the magnetic resonance imaging (MRI) findings of invasive breast cancer in different histopathological types (invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and mixed ductal-lobular carcinoma (MDLC)) and different histological grades.

METHODS: A retrospective review was made of 1256 patients who underwent breast MRI at our hospital between January 2015 and December 2018. A total of 152 lesions (27 ILC, 102 IDC, 23 MDLC and 20 grade 1, 83 grade 2 and 49 grade 3) were included in the study. All the lesions were evaluated according to size, shape, margin, dynamic curve, ADC value and T2 signal intensity ratio (SIR).

RESULTS: Most of the lesions tended to show type 2 and type 3 dynamic curve, type 1 dynamic curve was more commonly seen in ILC and grade 1 groups. IDC showed higher T2 SIR than the other types and grade 3 showed higher T2 SIR than other grades (p< 0,05) There was no statistically significant difference between the groups according to morphological features and mean ADC values (p > 0,05).

CONCLUSION: T2 SIR and dynamic curve can help the radiologists predict histopathological findings while morphological features and ADC values were not helpful in distinguishing histological types and grades.}, } @article {pmid33581714, year = {2021}, author = {Saeed, U and Uppal, SR and Piracha, ZZ and Rasheed, A and Aftab, Z and Zaheer, H and Uppal, R}, title = {Evaluation of SARS-CoV-2 antigen-based rapid diagnostic kits in Pakistan: formulation of COVID-19 national testing strategy.}, journal = {Virology journal}, volume = {18}, number = {1}, pages = {34}, pmid = {33581714}, issn = {1743-422X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology/*isolation & purification ; COVID-19/*diagnosis/epidemiology/immunology/virology ; COVID-19 Serological Testing/*methods ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; SARS-CoV-2/genetics/immunology/*isolation & purification ; Young Adult ; }, abstract = {Rapid diagnosis of SARS-CoV-2 during pandemic enables timely treatment and prevention of COVID-19. Evaluating the accuracy and reliability of rapid diagnostic testing kits is crucial for surveillance and diagnosis of SARS-CoV-2 infections in general population, injection drug users, multi-transfused populations, healthcare workers, prisoners, barbers and other high risk populations. The aim of this study was to evaluate performance and effectiveness of nasopharyngeal swab (NSP) and saliva based rapid antigen detection testing kits in comparison with USFDA approved triple target gold standard real-time polymerase chain reaction. A cross-sectional study was conducted on 33,000 COVID-19 suspected patients. From RT-PCR positive patients, nasopharyngeal swab (NSP) and saliva samples were obtained for evaluation of rapid COVID-19 testing kits (RDT). 100/33,000 (0.3%) of specimens were RT-PCR positive for SARS-CoV-2. Among RT-PCR positive, 62% were males, 34% were females, and 4% were children. The NSP-RDT (Lepu Medical China) analysis revealed 53% reactivity among males, 58% reactivity among females, and 25% reactivity among children. However saliva based RDT (Lepu Medical China) analysis showed 21% reactivity among males and 23% among females, and no reactivity in children. False negative results were significantly more pronounced in saliva based RDT as compared to NSP-RDT. The sensitivity of these NSP-RDT and saliva based RDT were 52% and 21% respectively. The RDTs evaluated in this study showed limited sensitivities in comparison to gold standard RT-PCR, indicating that there is a dire need in Pakistan for development of suitable testing to improve accurate COVID-19 diagnosis in line with national demands.}, } @article {pmid33580464, year = {2021}, author = {Xu, C and Gu, Z and Liu, J and Lin, X and Wang, C and Li, J and Fu, Y and Cheng, X and Zhuang, Z}, title = {Adenosquamous carcinoma of the breast: a population-based study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {28}, number = {4}, pages = {848-858}, pmid = {33580464}, issn = {1880-4233}, support = {YP18M03//Shanghai Yangpu district science projects/ ; }, mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Adenosquamous/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Carcinoma, Squamous Cell/mortality/pathology/therapy ; Female ; Humans ; Mastectomy/statistics & numerical data ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; SEER Program ; }, abstract = {BACKGROUND: To summarize the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC).

METHODS: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology, and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016.

RESULTS: ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC. ASC patients underwent the similar surgical and systematic treatment as IDC, only with less radiotherapy. Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all p < 0.05 for BCSM and OS). ASC was not an independent prognosis factor of breast cancer. After propensity score matching (PSM), no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the 5-year survival rate of ASC was 63.5%, which was far less than that in ASC of HR-negative (81.0%). Multivariate analysis showed that older age (age > 60) and advanced AJCC-stage were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC.

CONCLUSIONS: ASC has unique clinicopathological characteristics and prognosis. It is imperative to focus on a more precise and personalized treatment management of ASC patients.}, } @article {pmid33579357, year = {2021}, author = {Khatri, R and Petry, SF and Linn, T}, title = {Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration.}, journal = {Stem cell research & therapy}, volume = {12}, number = {1}, pages = {121}, pmid = {33579357}, issn = {1757-6512}, mesh = {Animals ; *Diabetes Mellitus, Experimental/therapy ; Insulin ; *Islets of Langerhans ; *Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Nude ; Streptozocin ; }, abstract = {BACKGROUND: Type 1 diabetes mellitus (T1D) is characterized by the autoimmune destruction of the pancreatic β cells. The transplantation of mesenchymal stromal/stem cells (MSC) was reported to rescue the damaged pancreatic niche. However, there is an ongoing discussion on whether direct physical contact between MSC and pancreatic islets results in a superior outcome as opposed to indirect effects of soluble factors released from the MSC entrapped in the lung microvasculature after systemic administration. Hence, MSC were studied in direct contact (DC) and indirect contact (IDC) with murine pancreatic β cell line MIN6-cells damaged by nitrosourea derivative streptozotocin (STZ) in vitro. Further, the protective and antidiabetic outcome of MSC transplantation was evaluated through the intrapancreatic route (IPR) and intravenous route (IVR) in STZ-induced diabetic NMRI nude mice.

METHODS: MSC were investigated in culture with STZ-damaged MIN6-cells, either under direct contact (DC) or separated through a semi-permeable membrane (IDC). Moreover, multiple low doses of STZ were administered to NMRI nude mice for the induction of hyperglycemia. 0.5 × 10[6] adipose-derived mesenchymal stem cells (ADMSC) were transferred through direct injection into the pancreas (IPR) or the tail vein (IVR), respectively. Bromodeoxyuridine (BrdU) was injected for the detection of proliferating islet cells in vivo, and real-time polymerase chain reaction (RT-PCR) was employed for the measurement of the expression of growth factor and immunomodulatory genes in the murine pancreas and human MSC. Phosphorylation of AKT and ERK was analyzed with Western blotting.

RESULTS: The administration of MSC through IPR ameliorated hyperglycemia in contrast to IVR, STZ, and non-diabetic control in a 30-day window. IPR resulted in a higher number of replicating islet cells, number of islets, islet area, growth factor (EGF), and balancing of the Th1/Th2 response in vivo. Physical contact also provided a superior protection to MIN6-cells from STZ through the AKT and ERK pathway in vitro in comparison with IDC.

CONCLUSION: Our study suggests that the physical contact between MSC and pancreatic islet cells is required to fully unfold their protective potential.}, } @article {pmid33572420, year = {2021}, author = {Li, H and Ning, T and Yu, F and Chen, Y and Zhang, B and Wang, S}, title = {Raman Microspectroscopic Investigation and Classification of Breast Cancer Pathological Characteristics.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {4}, pages = {}, pmid = {33572420}, issn = {1420-3049}, support = {61911530695//National Natural Science Foundation of China/ ; }, mesh = {Adenocarcinoma, Mucinous/*pathology/surgery ; Algorithms ; Breast Neoplasms/*classification/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Papillary/*pathology/surgery ; Case-Control Studies ; Discriminant Analysis ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Principal Component Analysis ; Spectrum Analysis, Raman/*methods ; }, abstract = {Breast cancer is one of the major cancers of women in the world. Despite significant progress in its treatment, an early diagnosis can effectively reduce its incidence rate and mortality. To improve the reliability of Raman-based tumor detection and analysis methods, we conducted an ex vivo study to unveil the compositional features of healthy control (HC), solid papillary carcinoma (SPC), mucinous carcinoma (MC), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissue samples. Following the identification of biological variations occurring as a result of cancer invasion, principal component analysis followed by linear discriminate analysis (PCA-LDA) algorithm were adopted to distinguish spectral variations among different breast tissue groups. The achieved results confirmed that after training, the constructed classification model combined with the leave-one-out cross-validation (LOOCV) method was able to distinguish the different breast tissue types with 100% overall accuracy. The present study demonstrates that Raman spectroscopy combined with multivariate analysis technology has considerable potential for improving the efficiency and performance of breast cancer diagnosis.}, } @article {pmid33567280, year = {2021}, author = {Greulich, F and Wierer, M and Mechtidou, A and Gonzalez-Garcia, O and Uhlenhaut, NH}, title = {The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers.}, journal = {Cell reports}, volume = {34}, number = {6}, pages = {108742}, pmid = {33567280}, issn = {2211-1247}, mesh = {Animals ; Enhancer Elements, Genetic/*immunology ; Inflammation/genetics/immunology ; Macrophages/*immunology ; Mice ; *Multiprotein Complexes/genetics/immunology ; *RNA-Seq ; *Receptors, Glucocorticoid/genetics/immunology ; Transcription, Genetic/*immunology ; }, abstract = {Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.}, } @article {pmid33565307, year = {2021}, author = {Seckin, ZI and Libertin, CR and Brumble, LM}, title = {Serologic screening and infectious diseases consultation in renal transplant candidates for measles, mumps, rubella and varicella.}, journal = {Romanian journal of internal medicine = Revue roumaine de medecine interne}, volume = {59}, number = {2}, pages = {159-165}, doi = {10.2478/rjim-2020-0036}, pmid = {33565307}, issn = {2501-062X}, mesh = {Antibodies, Viral/blood ; Chickenpox/*diagnosis/prevention & control ; Humans ; Immunoglobulin G/blood ; *Kidney Transplantation ; Measles/*diagnosis/prevention & control ; Mumps/*diagnosis/prevention & control ; *Preoperative Care ; Referral and Consultation ; Retrospective Studies ; Rubella/*diagnosis/prevention & control ; Vaccination ; }, abstract = {Background. Renal transplant recipients are at increased risk for developing complications of vaccine-preventable diseases. They benefit from a comprehensive pre-transplant evaluation when they might safely receive live vaccines. The primary aim of our study was to investigate the number of renal transplant recipients who were evaluated for serologic status against measles, mumps, rubella (MMR), and varicella. Secondarily, we investigated if pre-transplant Infectious Diseases consultation (IDC) improved vaccination rates.Methods. We retrospectively analyzed 282 kidney-alone and kidney-plus adult transplant recipients who were born in or after 1957. Patients were evaluated at Mayo Clinic, Florida Transplant Center between January 2015 and December 2017. Serologic status evaluation and vaccination rates were compared in two groups created based on IDC and no ID consultation (NIDC).Results. 235 (83%) of a total 282 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 235 IDC candidates. Among the IDC patients, mumps, measles and rubella IgG serologies were performed in 7 (3%), 143 (61%) and 144 (61%), respectively. Among 44 patients seronegative for any of MMR, 24 (55%) were vaccinated. Ten (66%) of 15 varicella seronegative patients were vaccinated. Zostavax was not given to 18% of IDC patients. Zostavax and MMR were administered more frequently in the IDC group compared to NIDC (p < .001 and p = 0.0016, respectively).Conclusion. Although the majority of patients had IDC, the screening rate for MMR serologies was lower than varicella. A protocol-driven serologic screening similar to the one for VZV is required for MMR. Pre-transplant IDC increases vaccination rates.}, } @article {pmid33563872, year = {2021}, author = {Ohno, M and Ohno, N and Miyati, T and Kawashima, H and Kozaka, K and Matsuura, Y and Gabata, T and Kobayashi, S}, title = {Triexponential Diffusion Analysis of Diffusion-weighted Imaging for Breast Ductal Carcinoma in Situ and Invasive Ductal Carcinoma.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {20}, number = {4}, pages = {396-403}, pmid = {33563872}, issn = {1880-2206}, mesh = {Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Diffusion Magnetic Resonance Imaging ; Echo-Planar Imaging ; Female ; Humans ; }, abstract = {PURPOSE: To obtain detailed information in breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) using triexponential diffusion analysis.

METHODS: Diffusion-weighted images (DWI) of the breast were obtained using single-shot diffusion echo-planar imaging with 15 b-values. Mean signal intensities at each b-value were measured in the DCIS and IDC lesions and fitted with the triexponential function based on a two-step approach: slow-restricted diffusion coefficient (Ds) was initially determined using a monoexponential function with b-values > 800 s/mm[2]. The diffusion coefficient of free water at 37°C was assigned to the fast-free diffusion coefficient (Df). Finally, the perfusion-related diffusion coefficient (Dp) was derived using all the b-values. Furthermore, biexponential analysis was performed to obtain the perfusion-related diffusion coefficient (D*) and the perfusion-independent diffusion coefficient (D). Monoexponential analysis was performed to obtain the apparent diffusion coefficient (ADC). The sensitivity and specificity of the aforementioned diffusion coefficients for distinguishing between DCIS and IDC were evaluated using the pathological results.

RESULTS: The Ds, D, and ADC of DCIS were significantly higher than those of IDC (P < 0.01 for all). There was no significant correlation between Dp and Ds, but there was a weak correlation between D* and D. The combination of Dp and Ds showed higher sensitivity and specificity (85.9% and 71.4%, respectively), compared to the combination of D* and D (81.5% and 33.3%, respectively).

CONCLUSION: Triexponential analysis can provide detailed diffusion information for breast tumors that can be used to differentiate between DCIS and IDC.}, } @article {pmid33562262, year = {2021}, author = {Yanagihara, R and Berry, MJ and Carson, MJ and Chang, SP and Corliss, H and Cox, MB and Haddad, G and Hohmann, C and Kelley, ST and Lee, ESY and Link, BG and Noel, RJ and Pickrel, J and Porter, JT and Quirk, GJ and Samuel, T and Stiles, JK and Sy, AU and Taira, DA and Trepka, MJ and Villalta, F and Wiese, TE}, title = {Building a Diverse Workforce and Thinkforce to Reduce Health Disparities.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33562262}, issn = {1660-4601}, support = {U54 MD007579/MD/NIMHD NIH HHS/United States ; U54 MD007597/MD/NIMHD NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 MD013376/MD/NIMHD NIH HHS/United States ; U54 MD007592/MD/NIMHD NIH HHS/United States ; U54 MD007602/MD/NIMHD NIH HHS/United States ; U24MD015970/NH/NIH HHS/United States ; U54 MD012397/MD/NIMHD NIH HHS/United States ; G12 MD007601/MD/NIMHD NIH HHS/United States ; R01 DK047320/DK/NIDDK NIH HHS/United States ; U54 MD007585/MD/NIMHD NIH HHS/United States ; U54 MD007586/MD/NIMHD NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; U54 MD007582/MD/NIMHD NIH HHS/United States ; U54 MD012393/MD/NIMHD NIH HHS/United States ; T32 AI007281/AI/NIAID NIH HHS/United States ; U54 MD013368/MD/NIMHD NIH HHS/United States ; U54 MD007595/MD/NIMHD NIH HHS/United States ; U13 MD014961/MD/NIMHD NIH HHS/United States ; }, mesh = {*Biomedical Research ; Humans ; Maryland ; *Minority Groups ; Research Personnel ; Workforce ; }, abstract = {The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the "workforce") and the harnessing of the heterogeneity of thought (the "thinkforce") to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success.}, } @article {pmid33561470, year = {2021}, author = {Kabay, S and Kabay, SC}, title = {The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results.}, journal = {Urology}, volume = {153}, number = {}, pages = {49-55}, doi = {10.1016/j.urology.2021.01.044}, pmid = {33561470}, issn = {1527-9995}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lower Urinary Tract Symptoms/etiology/*therapy ; Male ; Middle Aged ; Parkinson Disease/complications ; Prospective Studies ; *Tibial Nerve ; Time Factors ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/*therapy ; Urodynamics ; }, abstract = {OBJECTIVE: To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months.

METHODS: After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3[rd], 6[th], 9[th],12[th] and 24[th] month.

RESULTS: A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P ˃.05).

CONCLUSIONS: These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.}, } @article {pmid33558501, year = {2021}, author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P}, title = {Publisher Correction: Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {989}, doi = {10.1038/s41467-021-21406-x}, pmid = {33558501}, issn = {2041-1723}, } @article {pmid33556643, year = {2021}, author = {Novikoff, A and O'Brien, SL and Bernecker, M and Grandl, G and Kleinert, M and Knerr, PJ and Stemmer, K and Klingenspor, M and Zeigerer, A and DiMarchi, R and Tschöp, MH and Finan, B and Calebiro, D and Müller, TD}, title = {Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists.}, journal = {Molecular metabolism}, volume = {49}, number = {}, pages = {101181}, pmid = {33556643}, issn = {2212-8778}, support = {/WT_/Wellcome Trust/United Kingdom ; 212313/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Gastric Inhibitory Polypeptide/pharmacology ; Glucagon-Like Peptide 1/*analogs & derivatives/*metabolism ; HEK293 Cells ; Humans ; Ligands ; Peptides/pharmacology ; Receptors, Gastrointestinal Hormone/*metabolism ; Signal Transduction/*drug effects ; }, abstract = {OBJECTIVE: We assessed the spatiotemporal GLP-1 and GIP receptor signaling, trafficking, and recycling dynamics of GIPR mono-agonists, GLP-1R mono-agonists including semaglutide, and GLP-1/GIP dual-agonists MAR709 and tirzepatide.

METHODS: Receptor G protein recruitment and internalization/trafficking dynamics were assessed using bioluminescence resonance energy transfer (BRET)-based technology and live-cell HILO microscopy.

RESULTS: Relative to native and acylated GLP-1 agonists, MAR709 and tirzepatide showed preserved maximal cAMP production despite partial Gαs recruitment paralleled by diminished ligand-induced receptor internalization at both target receptors. Despite MAR709's lower internalization rate, GLP-1R co-localization with Rab11-associated recycling endosomes was not different between MAR709 and GLP-1R specific mono-agonists.

CONCLUSIONS: Our data indicated that MAR709 and tirzepatide induce unique spatiotemporal GLP-1 and GIP receptor signaling, trafficking, and recycling dynamics relative to native peptides, semaglutide, and matched mono-agonist controls. These findings support the hypothesis that the structure of GLP-1/GIP dual-agonists confer a biased agonism that, in addition to its influence on intracellular signaling, uniquely modulates receptor trafficking.}, } @article {pmid33554951, year = {2020}, author = {Şahin, S and Cakir, A and Gonul, II and Seckin, S and Uluoglu, O}, title = {Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.}, journal = {Annali italiani di chirurgia}, volume = {91}, number = {}, pages = {583-591}, pmid = {33554951}, issn = {2239-253X}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Prognosis ; Receptor, IGF Type 1/*genetics ; }, abstract = {OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.

MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.

RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025).

CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis.

KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.}, } @article {pmid33551925, year = {2020}, author = {Gershgoren, L and Blatt, A and Sela, T and Tenenbaum, G}, title = {Does the League Table Lie? The Development and Validation of the Perceived Performance in Team Sports Questionnaire (PPTSQ).}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {615018}, pmid = {33551925}, issn = {1664-1078}, abstract = {Objective performance measures are vastly used in sport psychology despite their inherent limitations (e.g., unaccounted baseline differences). Founded on the nature of group goals in team sports, we aimed at developing the Perceived Performance in Team Sports Questionnaire (PPTSQ) to capture the team members' perception of their team's performance. Accordingly, three dimensions were hypothesized: effort investment, skills execution, and perceived outcome. To measure these dimensions, items were generated to address the players' perception of their team performance as a whole. Four samples of athletes were used to test the psychometric properties of the PPTSQ: professional (n = 231), collegiate (n = 222), professional-retest (n = 89), and mixed professional-collegiate (n = 139). Exploratory and confirmatory factor analyses were used to estimate construct and content validities. These procedures revealed a better data fit to a two-dimensional model that consists of effort investment and perceived outcome. The reliability analyses for the PPTSQ provide satisfactory evidence that the questionnaire is a reliable measure of perceived performance in team sport. Adequate internal consistency emerged for both dimensions (0.75 < ω < 0.89). Furthermore, a high correlation was obtained for temporal stability. Concurrent validity was addressed by correlating the PPTSQ scores with the Group Environment Questionnaire and the Team Assessment Diagnostic Instrument. Correlational analysis between the PPTSQ and an objective measure of performance was used to test its predictive validity. The correlations strongly support the concurrent and predictive validities of the PPTSQ. We conclude that our perceived performance questionnaire can address various objective measures shortcomings (e.g., considering base-rate biases) resulting in a more meaningful team performance metric. Implication of the PPTSQ for sport psychology research and applied work enhancement are discussed in detail.}, } @article {pmid33548588, year = {2021}, author = {Monib, S and Anis, K and Habashy, H}, title = {Routine cavity shaves following breast conserving surgery; friend or foe?.}, journal = {Surgical oncology}, volume = {37}, number = {}, pages = {101521}, doi = {10.1016/j.suronc.2021.101521}, pmid = {33548588}, issn = {1879-3320}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma/pathology ; Female ; Humans ; *Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: Radial margin status is considered one of the most important prognostic predictor for patients undergoing breast-conserving surgery (BCT), not only related to regional recurrence but also to 5y survival, especially in patients with invasive disease.

AIM: While our primary aim was to evaluate whether doing routine radial cavity shaves following at the time of primary conservative breast surgery will decrease the need for a second operation or not, our secondary aim was to assess time added to the operation to resect and mark the radial shaves, as well as patients' satisfaction with the results.

MATERIAL AND METHODS: We have conducted a case series prospective analysis, including158 patients who underwent breast-conserving surgery looking into the histological status of resection margins and radial shaves, added time taken to take and mark the shaves as well as patients' satisfaction.

RESULTS: 158 female breast cancer patients have been included in our analysis, the mean age was 56 years; total number of lesions was 160. While 89.3% of lesions were palpable, 10.6% were not requiring wire-guided localisation. Mean tumour size was 24 mm SD 7, final histology revealed that 86.8% lesion was invasive ductal carcinoma, 5.6% invasive lobular carcinoma, 1.2% medullary carcinoma. 12.4% had invasive disease as well as DCIS, and 1.8% had DCIS only with no invasive disease. Mean preoperative breast volume was 723 ml, Mean wide local excision specimen weight was 73 g, and mean shave weight was 1.6 g. Total number of radial margins was 640, 81.8% was clear, 14.6% was close, and 3.4% was involved. Total number of shaves was 640 out of which 98.7% was clear 0.7% was close and 0.4% was involved. Out of the 160 lesions, 3.7% required a second procedure to clear margins, out of which 2.5% had re-excision for close or involved single shaves each while 1.2% had mastectomy due to close or involved two shaves each. Average time utilised in resection of radial shaves and marking was 7 min 0.6% of patients developed a haematoma, 1.8% had a Seroma, and 1.2% had wound infection. Mean hospital stay was 1day SD 1.

CONCLUSION: Routine radial cavity shaves not only ensure microscopic clearance, reduce the need for re-excision with no significant added operating time but also has no impact on patients' satisfaction.}, } @article {pmid33545323, year = {2021}, author = {Leikin-Frenkel, A and Liraz-Zaltsman, S and Hollander, KS and Atrakchi, D and Ravid, O and Rand, D and Kandel-Kfir, M and Israelov, H and Cohen, H and Kamari, Y and Shaish, A and Harats, D and Schnaider-Beeri, M and Cooper, I}, title = {Dietary alpha linolenic acid in pregnant mice and during weaning increases brain docosahexaenoic acid and improves recognition memory in the offspring.}, journal = {The Journal of nutritional biochemistry}, volume = {91}, number = {}, pages = {108597}, doi = {10.1016/j.jnutbio.2021.108597}, pmid = {33545323}, issn = {1873-4847}, mesh = {Animals ; Animals, Newborn ; Brain/drug effects/*metabolism ; *Dietary Supplements ; Docosahexaenoic Acids/*metabolism ; Female ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Weaning ; alpha-Linolenic Acid/*pharmacology ; }, abstract = {Docosahexaenoic acid (DHA) is critical for normal brain development and function. DHA is in danger of being significantly reduced in the human food supply, and the question of whether its metabolic precursor, the essential n-3 alpha linolenic acid (ALA) during pregnancy, can support fetal brain DHA levels for optimal neurodevelopment, is fundamental. Female mice were fed either ALA-enriched or Control diet during pregnancy and lactation. The direct effect of maternal dietary ALA on lipids was analyzed in liver, red blood cells, brain and brain vasculature, together with genes of fatty acid metabolism and transport in three-week-old offspring. The long-term effect of maternal dietary ALA on brain fatty acids and memory was studied in 19-week-old offspring. Three-week-old ALA offspring showed higher levels of n-3 fatty acids in liver, red blood cell, blood-brain barrier (BBB) vasculature and brain parenchyma, DHA enrichment in brain phospholipids and higher gene and protein expression of the DHA transporter, major facilitator superfamily domain containing 2a, compared to Controls. 19-week-old ALA offspring showed higher brain DHA levels and better memory performance than Controls. The increased brain DHA levels induced by maternal dietary ALA during pregnancy-lactation, together with the up-regulated levels of major facilitator superfamily domain containing 2a, may indicate a mode for greater DHA uptake with long-term impact on better memory in ALA offspring.}, } @article {pmid33542123, year = {2021}, author = {Jones, KM and Cook-Deegan, R and Rotimi, CN and Callier, SL and Bentley, AR and Stevens, H and Phillips, KA and Jansen, JP and Weyant, CF and Roberts, DE and Zielinski, D and Erlich, Y and Garrison, NA and Carroll, SR and Ossorio, PN and Moreau, Y and Wang, M}, title = {Complicated legacies: The human genome at 20.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {564-569}, pmid = {33542123}, issn = {1095-9203}, support = {P2C HD044964/HD/NICHD NIH HHS/United States ; R01 CA221870/CA/NCI NIH HHS/United States ; R01 CA237118/CA/NCI NIH HHS/United States ; U01 HG009599/HG/NHGRI NIH HHS/United States ; }, } @article {pmid33541824, year = {2021}, author = {Yoshida, S and Koshima, I and Imai, H and Uchiki, T and Sasaki, A and Fujioka, Y and Nagamatsu, S and Yokota, K and Yamashita, S}, title = {Modified intraoperative distal compression method for lymphaticovenous anastomosis with high success and a low venous reflux rates.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {74}, number = {9}, pages = {2050-2058}, doi = {10.1016/j.bjps.2020.12.103}, pmid = {33541824}, issn = {1878-0539}, mesh = {Anastomosis, Surgical/*methods ; *Compression Bandages ; Humans ; Intraoperative Care ; Lower Extremity/*blood supply/surgery ; Lymphatic Vessels/anatomy & histology/*surgery ; Lymphedema/*surgery ; Microcirculation ; Microsurgery/*methods ; Treatment Outcome ; Veins/*surgery ; }, abstract = {INTRODUCTION: For successful lymphaticovenous anastomosis (LVA), it is important to create anastomoses with high flow to maintain patency. To ensure that this can be achieved, we compared the efficacy of a modified intraoperative distal compression (IDC) technique with the conventional no compression (NC) method for lower limb lymphedema.

PATIENTS AND METHODS: In the IDC group, compression was applied to an area of the foot distal to the first LVA site. After completion of the first LVA, the distal compression was extended over the first LVA site to the distal end of the second LVA site.

RESULTS: There was no significant difference between the IDC (n = 25) and NC (n = 25) groups in detection rate. However, significant differences were observed in lymphatic vessel diameter and LVA success rate. No intraoperative anastomotic obstruction was seen at the conclusion of surgery. Intraoperative congestion with blood was detected in lymphatic vessels in 8 of 79 anastomoses (10.1%) in the NC group, but not in any cases in the IDC group (p = 0.002). There was a significant between-group difference in the rate of improvement in lymphedema between the IDC (16.1±3.6) and NC groups (14.0±3.4; p = 0.03).

DISCUSSION: IDC during LVA is thought to increase lymph flow in larger caliber lymphatics, leading to a high success rate and a low rate of venous reflux. IDC is beneficial when performing LVA.}, } @article {pmid33536239, year = {2021}, author = {Bühler, L and Maida, A and Vogl, ES and Georgiadi, A and Takacs, A and Kluth, O and Schürmann, A and Feuchtinger, A and von Toerne, C and Tsokanos, FF and Klepac, K and Wolff, G and Sakurai, M and Ekim Üstünel, B and Nawroth, P and Herzig, S}, title = {Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.}, journal = {Life science alliance}, volume = {4}, number = {4}, pages = {}, pmid = {33536239}, issn = {2575-1077}, mesh = {Animals ; Biomarkers ; *Energy Metabolism ; Fluorescent Antibody Technique ; Gene Expression ; Gene Knockdown Techniques ; Glucose/metabolism ; *Insulin Secretion ; Islets of Langerhans/cytology/metabolism ; Lipid Metabolism ; Lipocalins/blood/*genetics/*metabolism ; Liver/metabolism ; Male ; Mice ; Obesity/etiology/metabolism ; }, abstract = {Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.}, } @article {pmid33534078, year = {2021}, author = {Oses, G and Cases, C and Valduvieco, I and Farrús, B and Alonso, I and Caparrós, X and Mases, J and Muñoz-Guglielmetti, D and Biete, A and Castro, C and Escudero, E and Molina, M and Herreros, A and Saez, J and Mollà, M}, title = {Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {8}, pages = {1593-1600}, pmid = {33534078}, issn = {1699-3055}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*radiation effects ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/secondary/surgery ; Electrons/*therapeutic use ; Female ; Fibrosis/pathology ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; Postoperative Complications ; Prospective Studies ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Treatment Outcome ; }, abstract = {PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost.

MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0.

RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema.

CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.}, } @article {pmid33531875, year = {2020}, author = {Sołek, JM and Braun, M and Kalwas, M and Jesionek-Kupnicka, D and Romańska, HM}, title = {Adenoid cystic carcinoma of the breast - an uncommon malignancy with unpredictable clinical behaviour. A case series of three patients.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {24}, number = {4}, pages = {263-265}, pmid = {33531875}, issn = {1428-2526}, abstract = {Adenoid cystic carcinoma (AdCC) is a common tumour of the minor salivary gland, rarely seen in other anatomical locations. In particular, AdCC of the breast accounts for < 0.1% of patients diagnosed with breast cancer. Here we report our institutional experience with three cases of breast AdCC diagnosed between 2009 and 2017. Mean age of women included in the report was 53 (range from 41 to 62). One case was of no special subtype, two were solid variants and one presented with a component of invasive ductal carcinoma. At diagnosis in all cases neither lymph node involvement nor distal metastases were detected. All patients underwent surgical resection of the tumour - mastectomy or lumpectomy, followed by either adjuvant radiotherapy and chemotherapy (one case), chemotherapy without radiotherapy (one case) or no treatment (one case). Two patients were reported to develop metastatic disease. No deaths were recorded. In contrast to other anatomical locations AdCC of the breast is regarded as a rare tumour with low malignant potential. However, as shown in our case series, it can present as an aggressive disease with distal metastases, which calls for deep awareness among both pathologists and clinicians involved in the process of diagnosis and therapy.}, } @article {pmid33530236, year = {2021}, author = {Liu, N and Li, S and Jia, J and Qiao, Y and Li, Y}, title = {Advanced breast cancer with cachexia: A case report.}, journal = {Medicine}, volume = {100}, number = {4}, pages = {e24397}, pmid = {33530236}, issn = {1536-5964}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*complications/therapy ; Cachexia/etiology/*therapy ; Fatal Outcome ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; }, abstract = {RATIONALE: Cachexia is a clinically relevant syndrome in cancer that is associated with reduced tolerance to anticancer therapy, reduced quality of life, and reduced survival rates. Cachexia is most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers. It is rarely documented in breast cancer patients.

PATIENT CONCERNS: In our case report of a breast cancer patient with bone metastasis who was monitored throughout the course of her treatment, we document the development of cachexia using image analyses in relation to her metastatic burden. In the 2-year period, from April 10, 2015, to February 09, 2017, she lost 16% of her baseline weight. During this time, she was repeatedly hospitalized for chest tightness, edema of both lower limbs, numbness and pain in the left lower extremity and backache.

DIAGNOSES: Our patient was a 46-year-old premenopausal woman when she was firstly diagnosed. Several years after surgery for invasive ductal carcinoma of the left breast, she had multiple systemic bone metastases (the thoracic spine, the ribs, etc), lung metastasis, bilateral axillary lymph node metastasis, and metastasis of the right neck lymph node in IV area.

INTERVENTIONS: The patient completed 6 cycles of postoperative adjuvant chemotherapy and long-term endocrine therapy after a radical mastectomy for breast cancer. During the fourth progression, 6 cycles of rescue chemotherapy were performed. Local lumbosacral radiotherapy, and lumbar surgery were carried out to relieve symptoms after several progressions.

OUTCOMES: She became extremely thin, weighing only 50 kg at admission on July 23, 2018. This eventually led to multiple organ failure and death.

LESSONS: We noted a strong negative correlation between the abdominal muscle area and the metastatic tumor area at the second lumbar vertebral (L2) level. The monitoring of abdominal muscle wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and the extent of metastatic disease. This is especially true with breast cancer, where metastasis to bone is frequent. Our data from a computational tomography radiological quantification, may provide clinicians with early indications of the extent of cachexia in metastatic breast cancer patients.}, } @article {pmid33528758, year = {2021}, author = {Yang, L and Roy, M and Lin, H and Shen, Y and Albarracin, C and Huo, L and Chen, H and Wei, B and Bedrosian, I and Bu, H and Wu, Y}, title = {Validation of prognostic significance of the proposed uniform classification framework in neuroendocrine neoplasms of the breast.}, journal = {Breast cancer research and treatment}, volume = {186}, number = {2}, pages = {403-415}, pmid = {33528758}, issn = {1573-7217}, mesh = {*Breast Neoplasms ; *Carcinoma, Neuroendocrine/diagnosis ; Female ; Humans ; *Neuroendocrine Tumors ; Prognosis ; Survival Analysis ; }, abstract = {PURPOSE: A uniform classification framework for neuroendocrine neoplasms (NENs) in all the organ systems has been recently proposed by an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert panel. Based on the new classification system, the NENs of the breast are divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). This study is aimed to analysis the prognostic differences between NENs and invasive ductal carcinomas of no special type (IDCs-NST).

METHODS: The surveillance, epidemiology, and end results (SEER) database released on November 2018 was used for this study. Between 2003 and 2016, 361 NENs (NET = 239, NEC = 122) of the breast and 491,908 of IDCs-NST were identified. Survival analysis was performed for disease-specific survival (DSS) and overall survival (OS).

RESULTS: The 5-year DSS of NET, NEC, and IDC-NST was 63.39%, 46.00%, and 89.17%, respectively. And the 5-year OS of NET, NEC, and IDC-NST was 55.66%, 38.87%, and 83.17%, respectively. Within the same clinical stage or grade, NETs and NECs of the breast had worse DSS and OS than corresponding stage or grade IDCs-NST (all P < 0.050). In univariate and multivariate survival analysis, NENs of the breast had significantly worse DSS and OS than IDCs-NST (P < 0.001).

CONCLUSION: The universal classification framework for NEN allowed us to further refine the breast carcinoma with neuroendocrine differentiation as a unique pathologic and clinical entity, which has worse clinical outcome compared to IDC-NST.}, } @article {pmid33526379, year = {2021}, author = {Yamashita, Y and Tsunoda, H and Nagura, N and Kajiura, Y and Yoshida, A and Takei, J and Suzuki, K and Watanabe, T and Iwahira, Y and Yamauchi, H and Hayashi, N}, title = {Long-Term Oncologic Safety of Nipple-Sparing Mastectomy With Immediate Reconstruction.}, journal = {Clinical breast cancer}, volume = {21}, number = {4}, pages = {352-359}, doi = {10.1016/j.clbc.2021.01.002}, pmid = {33526379}, issn = {1938-0666}, mesh = {Adult ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Mammaplasty/*adverse effects ; Mastectomy, Subcutaneous/*adverse effects ; Middle Aged ; Nipples ; Patient Satisfaction ; Postoperative Complications/*epidemiology ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction.

PATIENTS AND METHODS: Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD < 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed.

RESULTS: The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43).

CONCLUSION: NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.}, } @article {pmid33523806, year = {2021}, author = {Hossain, MM and Saharkhiz, N and Konofagou, EE}, title = {Feasibility of Harmonic Motion Imaging Using a Single Transducer: In Vivo Imaging of Breast Cancer in a Mouse Model and Human Subjects.}, journal = {IEEE transactions on medical imaging}, volume = {40}, number = {5}, pages = {1390-1404}, pmid = {33523806}, issn = {1558-254X}, support = {R01 CA228275/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/diagnostic imaging ; *Elasticity Imaging Techniques ; Feasibility Studies ; Female ; Humans ; Mice ; Phantoms, Imaging ; Research Subjects ; Transducers ; }, abstract = {Harmonic motion imaging (HMI) interrogates the mechanical properties of tissues by simultaneously generating and tracking harmonic oscillation using focused ultrasound and imaging transducers, respectively. Instead of using two transducers, the objective of this work is to develop a single transducer HMI (ST-HMI) to both generate and track harmonic motion at "on-axis" to the force for facilitating data acquisition. In ST-HMI, the amplitude-modulated force was generated by modulating excitation pulse duration and tracking of motion was performed by transmitting tracking pulses interleaved between excitation pulses. The feasibility of ST-HMI was performed by imaging two elastic phantoms with three inclusions (N = 6) and comparing it with acoustic radiation force impulse (ARFI) imaging, in vivo longitudinal monitoring of 4T1, orthotropic breast cancer mice (N = 4), and patients (N = 3) with breast masses in vivo. Six inclusions with Young's moduli of 8, 10, 15, 20, 40, and 60 kPa were embedded in a 5 kPa background. The ST-HMI-derived peak-to-peak displacement (P2PD) successfully detected all inclusions with [Formula: see text] of the linear regression between the P2PD ratio of background to inclusion versus Young's moduli ratio of inclusion to background. The contrasts of 10 and 15 kPa inclusions were higher in ST-HMI than ARFI-derived images. In the mouse study, the median P2PD ratio of tumor to non-cancerous tissues was 3.0, 5.1, 6.1, and 7.7 at 1, 2, 3, and 4 weeks post-injection of the tumor cells, respectively. In the clinical study, ST-HMI detected breast masses including fibroadenoma, pseudo angiomatous stromal hyperplasia, and invasive ductal carcinoma with a P2PD ratio of 1.37, 1.61, and 1.78, respectively. These results indicate that ST-HMI can assess the mechanical properties of tissues via generation and tracking of harmonic motion "on-axis" to the ARF. This study is the first step towards translating ST-HMI in clinics.}, } @article {pmid33513952, year = {2021}, author = {O'Rourke, JA and Graham, MA}, title = {Gene Expression Responses to Sequential Nutrient Deficiency Stresses in Soybean.}, journal = {International journal of molecular sciences}, volume = {22}, number = {3}, pages = {}, pmid = {33513952}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//United States Department of Agriculture, Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Iron/metabolism ; Nutrients/*metabolism ; Phosphates/metabolism ; Plant Roots/genetics/growth & development ; Soybeans/*genetics/growth & development/metabolism ; Stress, Physiological/*genetics ; Transcriptome/*genetics ; }, abstract = {Throughout the growing season, crops experience a multitude of short periods of various abiotic stresses. These stress events have long-term impacts on plant performance and yield. It is imperative to improve our understanding of the genes and biological processes underlying plant stress tolerance to mitigate end of season yield loss. The majority of studies examining transcriptional changes induced by stress focus on single stress events. Few studies have been performed in model or crop species to examine transcriptional responses of plants exposed to repeated or sequential stress exposure, which better reflect field conditions. In this study, we examine the transcriptional profile of soybean plants exposed to iron deficiency stress followed by phosphate deficiency stress (-Fe-Pi). Comparing this response to previous studies, we identified a core suite of genes conserved across all repeated stress exposures (-Fe-Pi, -Fe-Fe, -Pi-Pi). Additionally, we determined transcriptional response to sequential stress exposure (-Fe-Pi) involves genes usually associated with reproduction, not stress responses. These findings highlight the plasticity of the plant transcriptome and the complexity of unraveling stress response pathways.}, } @article {pmid33510180, year = {2021}, author = {Heylmann, D and Ponath, V and Kindler, T and Kaina, B}, title = {Comparison of DNA repair and radiosensitivity of different blood cell populations.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {2478}, pmid = {33510180}, issn = {2045-2322}, mesh = {DNA Repair/*radiation effects ; Dendritic Cells/*metabolism ; *Gamma Rays ; Humans ; Lymphocytes/*metabolism ; Macrophages/*metabolism ; Myeloid Progenitor Cells/*metabolism ; Radiation Tolerance/*radiation effects ; }, abstract = {Despite the frequent use of ionising radiation (IR) in therapy and diagnostics and the unavoidable exposure to external radiation sources, our knowledge regarding the radiosensitivity of human blood cell populations is limited and published data, obtained under different experimental conditions, are heterogeneous. To compare the radiosensitivity of different hematopoietic cell populations, we set out to determine the responses of cells obtained from peripheral blood of healthy volunteers under identical conditions (resting, non-stimulated cells). First, we measured the radiation response of T cells (Treg, Th, CTL), B cells, NK cells, CD34+ progenitor cells and monocytes obtained from peripheral blood and monocyte-derived macrophages (Mph) and immature dendritic cells (iDC) ex vivo and show that T and B cells are highly sensitive, starting to undergo apoptosis following IR with a dose as low as 0.125 Gy. Importantly, there was no clear threshold dose and cell death/apoptosis increased up to a saturation level with a dose of 2 Gy. The sensitivity decreased in the order of T cells > NK and B cells > monocytes > macrophages and iDC. The data confirm a previous report that Mph and iDC are radiation-resistant compared to their progenitor monocytes. Although non-stimulated T and B cells were highly radiation-sensitive compared to monocytes and macrophages, they were competent in the repair of DNA double-strand breaks, as shown by a decline in γH2AX foci in the post-exposure period. CD34+ cells obtained from peripheral blood also showed γH2AX decline post-exposure, indicating they are repair competent. Granulocytes (CD15+) did not display any γH2AX staining following IR. Although peripheral blood lymphocytes, the main fraction are T cells, were significantly more radiation-sensitive than monocytes, they displayed the expression of the repair proteins XRCC1, ligase III and PARP-1, which were nearly non-expressed in monocytes. To assess whether monocytes are depleted in vivo following IR, we measured the amount of T cells and monocytes in cancer patients who received total-body radiation (TBR, 6 × 2 Gy). We observed that the number of T cells in the peripheral blood significantly declined already after the first day of TBR and remained at a low level, which was accompanied by an increase in the number of γH2AX foci in the surviving CD3+ T cell fraction. In contrast, the number of monocytes did not decline extensively, reflecting their radiation resistance compared to T cells. Monocytes also showed an accumulation of γH2AX foci in vivo, but the levels were significantly lower than in T cells. CD56+ NK cells displayed a response similar to T cells. The data support the notion that unstimulated T cell subfractions are nearly equally radiation sensitive. There are, however, remarkable differences in the radiation sensitivity between the lymphoid and the myeloid lineage, with lymphoid cells being significantly more sensitive than cells of the myeloid lineage. In the myeloid lineage, macrophages and iDCs were the most radio-resistant cell types.}, } @article {pmid33495219, year = {2021}, author = {Tewari, SG and Rajaram, K and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic Survival Adaptations of Plasmodium falciparum Exposed to Sublethal Doses of Fosmidomycin.}, journal = {Antimicrobial agents and chemotherapy}, volume = {65}, number = {4}, pages = {}, pmid = {33495219}, issn = {1098-6596}, support = {R01 AI065853/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; T32 AI007417/AI/NIAID NIH HHS/United States ; }, mesh = {*Antimalarials/therapeutic use ; *Apicoplasts ; *Fosfomycin/analogs & derivatives/pharmacology/therapeutic use ; Humans ; *Malaria, Falciparum/drug therapy ; Plasmodium falciparum/genetics ; }, abstract = {The malaria parasite Plasmodium falciparum contains the apicoplast organelle that synthesizes isoprenoids, which are metabolites necessary for posttranslational modification of Plasmodium proteins. We used fosmidomycin, an antibiotic that inhibits isoprenoid biosynthesis, to identify mechanisms that underlie the development of the parasite's adaptation to the drug at sublethal concentrations. We first determined a concentration of fosmidomycin that reduced parasite growth by ∼50% over one intraerythrocytic developmental cycle (IDC). At this dose, we maintained synchronous parasite cultures for one full IDC and collected metabolomic and transcriptomic data at multiple time points to capture global and stage-specific alterations. We integrated the data with a genome-scale metabolic model of P. falciparum to characterize the metabolic adaptations of the parasite in response to fosmidomycin treatment. Our simulations showed that, in treated parasites, the synthesis of purine-based nucleotides increased, whereas the synthesis of phosphatidylcholine during the trophozoite and schizont stages decreased. Specifically, the increased polyamine synthesis led to increased nucleotide synthesis, while the reduced methyl-group cycling led to reduced phospholipid synthesis and methyltransferase activities. These results indicate that fosmidomycin-treated parasites compensate for the loss of prenylation modifications by directly altering processes that affect nucleotide synthesis and ribosomal biogenesis to control the rate of RNA translation during the IDC. This also suggests that combination therapies with antibiotics that target the compensatory response of the parasite, such as nucleotide synthesis or ribosomal biogenesis, may be more effective than treating the parasite with fosmidomycin alone.}, } @article {pmid33484951, year = {2021}, author = {Lemmer, IL and Willemsen, N and Hilal, N and Bartelt, A}, title = {A guide to understanding endoplasmic reticulum stress in metabolic disorders.}, journal = {Molecular metabolism}, volume = {47}, number = {}, pages = {101169}, pmid = {33484951}, issn = {2212-8778}, mesh = {Adipocytes/metabolism ; Animals ; Autophagy ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/*physiology ; Humans ; Inflammation/metabolism ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases/*metabolism ; Obesity/metabolism ; Proteins/metabolism ; Ubiquitin ; Unfolded Protein Response ; }, abstract = {BACKGROUND: The global rise of metabolic disorders, such as obesity, type 2 diabetes, and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore disturbed ER function, known as "ER stress," is a key feature of metabolic disorders.

SCOPE OF REVIEW: As ER stress remains a poorly defined phenomenon, this review provides a general guide to understanding the nature, etiology, and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction.

MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell type-specific metabolic control by hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.}, } @article {pmid33483115, year = {2021}, author = {Cerea, S and Ghisi, M and Bottesi, G and Manoli, T and Carraro, E and Doron, G}, title = {Cognitive Behavioral Training Using a Mobile Application Reduces Body Image-Related Symptoms in High-Risk Female University Students: A Randomized Controlled Study.}, journal = {Behavior therapy}, volume = {52}, number = {1}, pages = {170-182}, doi = {10.1016/j.beth.2020.04.002}, pmid = {33483115}, issn = {1878-1888}, mesh = {*Body Dysmorphic Disorders/therapy ; Body Image ; Cognition ; Female ; Humans ; *Mobile Applications ; Students ; Universities ; }, abstract = {Body dissatisfaction is prevalent in young women, and is associated with symptoms of body dysmorphic disorder (BDD) and eating disorders (EDs). The aim of the study was to assess the efficacy of a mobile application, based on cognitive behavioral principles, in reducing body dissatisfaction and BDD/ED symptoms in female university students considered at high-risk of developing body image disorders (BIDs). Fifty university students at high-risk of developing BIDs (using self-report questionnaires assessing BIDs and the Structured Clinical Interview for DSM-5 Clinical Version) were randomized in two groups: immediate-use App group (iApp group; n = 25) and delayed-use App group (dApp group; n = 25). The iApp group started using the app at baseline for 16 days (T0 to T1). The dApp group waited for 16 days before starting to use the app (T1 to T2). Participants completed questionnaires at baseline (T0), 16 days from baseline (T1), and 32 days from baseline (T2). Repeated measure Analyses of Variance (ANOVAs) showed a Group (iApp vs. dApp) × Time (T0 vs. T1) interaction on BDD symptoms indicating medium effect size (partial eta squared) reductions in the iApp group compared to dApp group at T1; post-intervention means for BDD symptoms were under the cut-off for extreme body dissatisfaction/BDD symptoms in both groups. Pertaining to ED symptoms, no significant Group × Time interaction was detected. Training 3 minutes a day for 16 days with a CBT-based mobile application may lead to reductions in some forms of body dissatisfaction, including BDD symptoms in female university students at high-risk of developing BIDs. On the other hand, effects of the intervention on ED symptoms seem more limited.}, } @article {pmid33482684, year = {2021}, author = {Cochrane, K and Bell, JL and Heidel, RE and Orucevic, A}, title = {Adenosquamous carcinoma of the breast, an uncommon diagnosis with poor prognosis-Lessons learned from a 12-year analysis of the National Cancer Database.}, journal = {The breast journal}, volume = {27}, number = {2}, pages = {165-169}, doi = {10.1111/tbj.14135}, pmid = {33482684}, issn = {1524-4741}, mesh = {Breast ; *Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Adenosquamous/diagnosis ; *Carcinoma, Ductal, Breast ; Female ; Humans ; Prognosis ; }, abstract = {We compared the clinicopathologic characteristics and prognosis of adenosquamous carcinoma (ASQ) of the breast with invasive ductal carcinoma (IDC), utilizing the National Cancer Database (NCDB) from 2004 to 2015. 1 932 688 female patients had invasive breast carcinoma; 1 421 250 had IDC (73.5%); and 453 had ASQ (0.0002%). When compared to IDC, ASQ patients were significantly (P < .05) older and had grade 1 tumors; negative lymph nodes; ER/PR/HER2-negative tumors; and worse 5-year overall survival (64.9% vs 74%, respectively). Our study, largest to date on ASQ, revealed an aggressive carcinoma with a significantly worse prognosis than IDC. "Personalized medicine" treatment approach for patients with this uncommon carcinoma is needed.}, } @article {pmid33482449, year = {2021}, author = {Matsumoto, M and Yano, H and Otsubo, R and Tanaka, A and Nagayasu, T}, title = {Favorable survival with combined treatment in a metastatic breast cancer patient undergoing hemodialysis: A case report.}, journal = {International journal of surgery case reports}, volume = {79}, number = {}, pages = {206-209}, pmid = {33482449}, issn = {2210-2612}, abstract = {INTRODUCTION: Management of breast cancer patients undergoing hemodialysis (HD) is difficult because of a lack of evidence about drug selection, dose adjustment, and surgical procedures. We herein present a case of metastatic breast cancer in a patient undergoing HD.

PRESENTATION OF CASE: A 58-year-old Japanese woman with breast cancer undergoing HD underwent total mastectomy of the left breast and left axillary dissection. Histopathological examination revealed invasive ductal carcinoma, and the diagnosis was pT2N3cM0 Stage ⅢC. Immunostaining of the resected specimen indicated that the tumor was estrogen receptor-positive, progesterone receptor-negative, human epithelial growth factor receptor 2-positive, and the Ki-67 labeling index was 70%. A postoperative positron emission tomography/computed tomography (PET/CT) scan indicated fluorodeoxyglucose uptake in the supraclavicular nodes. She received adjuvant therapy of epirubicin and cyclophosphamide followed by docetaxel, trastuzumab (T-mab) and radiation therapy. However, she developed multiple liver metastases during adjuvant T-mab and hormone therapy. Therefore, her regimen was changed to trastuzumab emtansine (T-DM1) as first-line therapy, T-mab, pertuzumab (P-mab), and eribulin as second-line therapy, and T-mab, P-mab, and weekly paclitaxel as third-line therapy. Eventually, she was administered fourth-line treatment of T-mab, P-mab, and vinorelbine because of adverse events. She has survived more than 25 months after the initial detection of recurrence of breast cancer and maintained quality of life.

CONCLUSION: We report a case of breast cancer in a patient undergoing HD. It is very difficult to identify the appropriate drugs and dosages in patients undergoing HD to improve survival and quality of life.}, } @article {pmid33478862, year = {2021}, author = {Zhang, H and Ge, XY and Qiao, HQ}, title = {Analysis of prognostic risk factors in 3427 patients with invasive ductal carcinoma of breast: Results based on the SEER database.}, journal = {Asian journal of surgery}, volume = {44}, number = {3}, pages = {577-579}, doi = {10.1016/j.asjsur.2020.12.014}, pmid = {33478862}, issn = {0219-3108}, mesh = {Breast/pathology ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Risk Factors ; }, } @article {pmid33473040, year = {2021}, author = {Erdogan, O and Parlakgumus, A and Turan, U and Toyran, T and Irkorucu, O}, title = {Non-invasive ductal carcinoma within malignant phyllodes tumor of the breast.}, journal = {Nigerian journal of clinical practice}, volume = {24}, number = {1}, pages = {135-137}, doi = {10.4103/njcp.njcp_261_20}, pmid = {33473040}, issn = {1119-3077}, mesh = {Breast ; *Breast Neoplasms ; *Carcinoma, Ductal ; Female ; *Fibroadenoma ; Humans ; Middle Aged ; *Phyllodes Tumor/surgery ; }, abstract = {Phyllodes tumors are uncommon breast neoplasms that constitute of 1-2% of breast malignancies. The tumor can mimic fibroadenoma clinically, radiologically and histologically. Ductal carcinoma in-situ in the epithelial component of phyllodes tumor is very rare. When ductal carcinoma in-situ is detected within the specimen, the management of treatment changes completely. We report a rare case of low grade ductal carcinoma in-situ arising in a malignant phyllodes tumor in a 55-year-old female patient.}, } @article {pmid33469357, year = {2021}, author = {da Silva, JL and Rodrigues, FR and de Mesquita, GG and Fernandes, PV and Thuler, LCS and de Melo, AC}, title = {Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment.}, journal = {Breast cancer (Dove Medical Press)}, volume = {13}, number = {}, pages = {31-44}, pmid = {33469357}, issn = {1179-1314}, abstract = {OBJECTIVE: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC).

MATERIALS AND METHODS: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes.

RESULTS: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0-1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p <0.0001, respectively) and LNR (p <0.0001 and p <0.0001, respectively) showed significant association.

CONCLUSION: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.}, } @article {pmid33468979, year = {2020}, author = {Ogasawara, K and Hasebe, T and Nara, M and Nozaki, T and Oishi, S and Yoshihara, S}, title = {[A Case of Pancreatotomy of the Pancreatic Tail with a Preserved Residual Stomach Using ICG Fluorescence Method for Pancreatic Cancer after Gastrectomy of the Pyloric Side].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {2415-2417}, pmid = {33468979}, issn = {0385-0684}, mesh = {Fluorescence ; Gastrectomy ; *Gastric Stump ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/surgery ; *Stomach Neoplasms/surgery ; }, abstract = {A 53-year-old male had a history of gastrectomy of the pyloric side for gastric cancer and Billroth Ⅰ reconstruction done 20 years ago. The patient visited the gastrointestinal internal medical department of our hospital with abdominal pain as the chief complaint. Pancreatic cancer was diagnosed with the help of an abdominal CT, and he was then referred to our department. The preoperative disease stage was cT3, N0, M0, Stage ⅡA. As it was over 20 years since the previous surgery and the preoperative CT showed cardiac branches of the left inferior phrenic artery, we inferred that the residual stomach can be preserved. The blood flow was confirmed by the intraoperative ICG fluorescence method, and we then performed pancreatotomy of the pancreatic tail, preserving the stomach and a splenectomy. The pathologic findings were invasive ductal carcinoma, pT3, N1a, M0, Stage ⅡB, and R0. S-1 was administered orally as postoperative adjunctive chemotherapy. The postoperative course has been favorable without recurrence for 2 years. In case a pancreatotomy of the pancreatic tail is performed for cancer of the pancreatic body after gastrectomy of the pyloric side, it was considered that the intraoperative ICG fluorescence method was useful to confirm the blood flow of the residual stomach.}, } @article {pmid33468975, year = {2020}, author = {Nabeya, M and Maeda, N and Sato, Y and Suzuki, N and Takeda, S and Yamamoto, T and Kubo, H and Nagashima, Y and Yamamoto, S and Nagano, H}, title = {[A Case of Local Recurrence in the Reconstructed Breast Three Years after Reconstructive Surgery and Seven Years after Breast Cancer Surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {2403-2405}, pmid = {33468975}, issn = {0385-0684}, mesh = {*Breast Implants ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; *Mammaplasty ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; }, abstract = {In recent years, breast reconstruction has been increasingly performed in breast cancer surgery with improving the appearance of the breast. We report a case of local breast cancer recurrence after artificial breast reconstruction. The patient was a 52-year-old woman. She had undergone total mastectomy for left breast cancer 11 years ago, and reconstruction with breast implant 3 years ago. She presented to our hospital with the chief complaint of skin redness and induration of the reconstructed breast. A core needle biopsy was performed, and its results showed in the invasive ductal carcinoma. She had an operation of resection of tumor and reconstruction implant. As a result of histopathological diagnosis, it was a local recurrence of breast cancer 11 years ago. After the surgery, she underwent endocrine therapy and there is no recurrence. As the increase in the number of cases of breast reconstruction, the number of recurrences in the reconstructed breast is expected to increase the future. The treatment strategy for cases of local recurrence after breast reconstruction is currently under review, the accumulation of evidence is necessary.}, } @article {pmid33468958, year = {2020}, author = {Aoki, K and Kametaka, H and Makino, H and Fukada, T and Akiyama, T and Hyakutake, Y and Yoshida, H and Mitomi, H and Seike, K}, title = {[A Case of Primary Breast Cancer and Gastric Cancer Metastasis to the Skin-Usefulness of Immunohistochemistry in Differentiating Primary Breast Cancer from Metastatic Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {2352-2354}, pmid = {33468958}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/surgery ; Female ; Gastrectomy ; Humans ; Immunohistochemistry ; Mastectomy ; *Stomach Neoplasms/surgery ; }, abstract = {We herein report the case of a 76-year-old female patient who had undergone gastrectomy for advanced gastric cancer (histologically tubular adenocarcinoma)before 5 months, presenting with abdominal skin tumor. A skin biopsy revealed tubular adenocarcinoma. Positron emission tomography-computed tomographic scanning detected right breast tumor. A partial mastectomy of the right breast and local resection of abdominal skin tumor were performed and both tumors depicted similar histology of tubular adenocarcinoma in routine pathological examination. Immunohistochemically, positive for CDX2 and MUC5AC in previously resected gastric cancer and skin tumor tissues, whereas negative for both antigens in breast cancer. Thus, the final pathological diagnosis demonstrated skin metastasis originating from gastric cancer and primary breast cancer(invasive ductal carcinoma)histologically mimicking gastric cancer. We emphasize difficulties in diagnosis of this situation and that immunohistochemistry is helpful to distinguish primary breast cancer from gastric cancer metastasizing to the breast.}, } @article {pmid33468859, year = {2020}, author = {Yamamuro, M and Konishi, J and Nozaki, Y and Ueno, M and Ishida, T and Kamo, N and Tanaka, N}, title = {[A Case of Lung Metastasis of the Breast Cancer with a Remarkable Response to Stereotactic Body Radiation Therapy(SBRT)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {1878-1880}, pmid = {33468859}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; *Lung Neoplasms/therapy ; Neoplasm Recurrence, Local ; *Radiosurgery ; Tegafur ; }, abstract = {A 69-year-old woman admitted to our hospital with the lump in the left breast. Further examination was performed for the lesion, and it was diagnosed as invasive ductal carcinoma. Partial resection and sentinel lymph node biopsy were performed. Pathological diagnosis was metaplastic carcinoma with squamous metaplasia. As the adjuvant treatment, docetaxel and cyclophosphamide(TC)therapy and radiotherapy was performed. Following the treatment of those, tegafur-uracil was administered for 2 years. Three years after the surgery, an isolated lung metastasis was revealed by CT. Capecitabine and cyclophosphamide(XC)therapy was administered, but not effective. Stereotactic body radiation therapy(SBRT)was performed for the lesion. As a result, the metastatic lesion was obscured. Drug therapy was stopped due to adverse events, and she is observed by no medication. Thirty-six months after SBRT and 78 months after the surgery, the patient is alive without recurrence. SBRT could be an effective treatment strategy for the oligometastais of the lung.}, } @article {pmid33468854, year = {2020}, author = {Okazaki, S and Takahashi, M and Fukahori, M and Taguchi, K and Minoshima, K and Hattori, S and Suematsu, Y and Saito, H and Teranishi, N and Wakabayashi, K and Itoh, Y}, title = {[A Case Report of Accessory Breast Cancer in the Right Axillary Region].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {1863-1865}, pmid = {33468854}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Axilla ; *Breast Diseases ; *Breast Neoplasms/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Node Excision ; Mammography ; }, abstract = {An 80-year-old woman visited a previous hospital complaining of a lump in the right axillary region. Because it was suspected of accessory breast cancer from the findings of image inspection, she was referred for surgery. Based on mammography and ultrasonography, both bilateral mammary glands were reported normal, but an irregular mass was found in the right axillary region. Resection biopsy showed adenocarcinoma like invasive ductal carcinoma. In addition, ER and PgR were positive. With a preoperative diagnosis of accessory breast cancer, she underwent wide local resection of the right axillary region with lymph-node dissection(Level Ⅰ), and local pedicle flap formation. Histopathological findings revealed that the tumor was composed of invasive ductal carcinoma. The center of tumor was consisted of ductal tissue discontinuous with normal mammary gland. So, a diagnosis of accessory breast cancer in the right axillary region was confirmed. She is currently in recurrence-free survival. Accessory breast cancer is relatively rare. We report a case of accessory breast cancer in the axillary region with some review of the literature.}, } @article {pmid33468814, year = {2020}, author = {Asano, Y and Kashiwagi, S and Kawano, Y and Kouhashi, R and Yabumoto, A and Ishihara, S and Goto, W and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Hirakawa, K and Ohira, M}, title = {[Effectiveness of Atezolizumab Combination Therapy for PD-L1(SP142)Positive Lung and Breast Double Cancer-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {1741-1743}, pmid = {33468814}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; Lung ; Mastectomy ; Middle Aged ; }, abstract = {The anti-PD-L1 antibody atezolizumab has become the standard of immunochemotherapy with the results of the international phase Ⅲ trials in lung cancer and breast cancer. We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer. A 56-years-old woman. She noticed a lump in her right breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonography revealed about 5 cm mass on the right mammary gland and axillary lymph nodes swelling. Core-needle biopsy was confirmed invasive ductal carcinoma(ER negative, PgR negative, HER2 negative, Ki-67 high expression). CT findings showed right mammary mass, right axillary lymph nodes swelling, liver mass, and lung tumor with mediastinal lymph nodes swelling. Therefore, a bronchoscopic biopsy was performed and a diagnosis of primary lung cancer was obtained. Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage ⅢA/B or ⅣA/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage ⅢB or Ⅳ triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.}, } @article {pmid33468810, year = {2020}, author = {Ishihara, S and Kashiwagi, S and Asano, Y and Kawano, Y and Kouhashi, R and Yabumoto, A and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {2089-2091}, pmid = {33468810}, issn = {0385-0684}, mesh = {Aged ; Axilla ; *Breast Neoplasms/drug therapy ; *Dermatitis/drug therapy/etiology ; Female ; Humans ; Metronidazole ; Trastuzumab/adverse effects ; }, abstract = {Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.}, } @article {pmid33468794, year = {2020}, author = {Tanaka, A and Nakayama, H and Ono, Y and Nukada, S and Amano, S and Katayama, Y and Osaragi, T and Tani, K and Masuda, M}, title = {[Case of Spindle Cell Carcinoma of the Breast Resistant Neoadjuvant Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {13}, pages = {2041-2043}, pmid = {33468794}, issn = {0385-0684}, mesh = {Aged ; Axilla ; *Breast Neoplasms/drug therapy/surgery ; *Carcinoma ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Neoadjuvant Therapy ; }, abstract = {We report a rare case of spindle cell carcinoma of the breast which grew rapidly during neoadjuvant chemotherapy. A 72- year-old female was presenting with chief complaint of a mass in the right breast; a tumor about 20 mm in size. Core needle biopsy of tumor revealed invasive ductal carcinoma and fine needle aspiration cytology of axillary lymph node was Class Ⅴ. So she was diagnosis breast cancer as cT2N1M0, cStage ⅡB. The tumor subtype was triple negative breast cancer (TNBC). She received the neoadjuvant chemotherapy by FEC100. After FEC 4 courses, we detected a huge and rapid growing breast mass of 40 mm by CT. She was administered received mastectomy and axillary lymph node dissection after 4 months from initial contact. Pathological finding was spindle cell carcinoma of the breast. Postoperatively, she was treated with weekly PTX for a total of 12 courses and radiation therapy for a right chest wall and supraclavicular fossa. Although the tumor was resistant for neoadjuvant chemotherapy, she is alive and well without metastasis for more than 3 years.}, } @article {pmid33466767, year = {2021}, author = {Mota-Romero, E and Tallón-Martín, B and García-Ruiz, MP and Puente-Fernandez, D and García-Caro, MP and Montoya-Juarez, R}, title = {Frailty, Complexity, and Priorities in the Use of Advanced Palliative Care Resources in Nursing Homes.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {1}, pages = {}, pmid = {33466767}, issn = {1648-9144}, mesh = {Cross-Sectional Studies ; *Frailty ; Humans ; Nursing Homes ; Palliative Care ; Spain ; }, abstract = {Background and objectives: This study aimed to determine the frailty, prognosis, complexity, and palliative care complexity of nursing home residents with palliative care needs and define the characteristics of the cases eligible for receiving advanced palliative care according to the resources available at each nursing home. Materials and Methods: In this multi-centre, descriptive, and cross-sectional study, trained nurses from eight nursing homes in southern Spain selected 149 residents with palliative care needs. The following instruments were used: the Frail-VIG index, the case complexity index (CCI), the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal), the palliative prognosis index, the Barthel index (dependency), Pfeiffer's test (cognitive impairment), and the Charlson comorbidity index. A consensus was reached on the complexity criteria of the Diagnostic Instrument of Complexity in Palliative Care that could be addressed in the nursing home (no priority) and those that required a one-off (priority 2) or full (priority 1) intervention of advanced palliative care resources. Non-parametric tests were used to compare non-priority patients and patients with some kind of priority. Results: A high percentage of residents presented frailty (80.6%), clinical complexity (80.5%), and palliative care complexity (65.8%). A lower percentage of residents had a poor prognosis (10.1%) and an extremely poor prognosis (2%). Twelve priority 1 and 14 priority 2 elements were identified as not matching the palliative care complexity elements that had been previously identified. Of the studied cases, 20.1% had priority 1 status and 38.3% had priority 2 status. Residents with some kind of priority had greater levels of dependency (p < 0.001), cognitive impairment (p < 0.001), and poorer prognoses (p < 0.001). Priority 1 patients exhibited higher rates of refractory delirium (p = 0.003), skin ulcers (p = 0.041), and dyspnoea (p = 0.020). Conclusions: The results indicate that there are high levels of frailty, clinical complexity, and palliative care complexity in nursing homes. The resources available at each nursing home must be considered to determine when advanced palliative care resources are required.}, } @article {pmid33462507, year = {2021}, author = {Gao, R and Bai, S and Henderson, YC and Lin, Y and Schalck, A and Yan, Y and Kumar, T and Hu, M and Sei, E and Davis, A and Wang, F and Shaitelman, SF and Wang, JR and Chen, K and Moulder, S and Lai, SY and Navin, NE}, title = {Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes.}, journal = {Nature biotechnology}, volume = {39}, number = {5}, pages = {599-608}, pmid = {33462507}, issn = {1546-1696}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA240526/CA/NCI NIH HHS/United States ; T32 CA217789/CA/NCI NIH HHS/United States ; R01 CA236864/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; *Clonal Evolution ; DNA Copy Number Variations/*genetics ; Gene Expression Regulation, Neoplastic ; Genomics/trends ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/genetics ; Single-Cell Analysis ; Transcriptome/*genetics ; Tumor Microenvironment/genetics ; }, abstract = {Single-cell transcriptomic analysis is widely used to study human tumors. However, it remains challenging to distinguish normal cell types in the tumor microenvironment from malignant cells and to resolve clonal substructure within the tumor. To address these challenges, we developed an integrative Bayesian segmentation approach called copy number karyotyping of aneuploid tumors (CopyKAT) to estimate genomic copy number profiles at an average genomic resolution of 5 Mb from read depth in high-throughput single-cell RNA sequencing (scRNA-seq) data. We applied CopyKAT to analyze 46,501 single cells from 21 tumors, including triple-negative breast cancer, pancreatic ductal adenocarcinoma, anaplastic thyroid cancer, invasive ductal carcinoma and glioblastoma, to accurately (98%) distinguish cancer cells from normal cell types. In three breast tumors, CopyKAT resolved clonal subpopulations that differed in the expression of cancer genes, such as KRAS, and signatures, including epithelial-to-mesenchymal transition, DNA repair, apoptosis and hypoxia. These data show that CopyKAT can aid in the analysis of scRNA-seq data in a variety of solid human tumors.}, } @article {pmid33462216, year = {2021}, author = {Deshpande, D and Agarwal, N and Fleming, T and Gaveriaux-Ruff, C and Klose, CSN and Tappe-Theodor, A and Kuner, R and Nawroth, P}, title = {Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {426}, pmid = {33462216}, issn = {2041-1723}, mesh = {Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus, Experimental/chemically induced/*complications ; Diabetic Neuropathies/etiology/*pathology ; Female ; Ganglia, Spinal/cytology/pathology ; Humans ; Lysosomes ; Male ; Mice ; Mice, Knockout ; Nociception/*physiology ; Pro-Opiomelanocortin/*deficiency/genetics ; Proteolysis ; Receptors, Opioid, mu/genetics/metabolism ; Sensory Receptor Cells/*pathology ; Streptozocin/toxicity ; }, abstract = {Painful neuropathy is a frequent complication in diabetes. Proopiomelanocortin (POMC) is an endogenous opioid precursor peptide, which plays a protective role against pain. Here, we report dysfunctional POMC-mediated antinociception in sensory neurons in diabetes. In streptozotocin-induced diabetic mice the Pomc promoter is repressed due to increased binding of NF-kB p50 subunit, leading to a loss in basal POMC level in peripheral nerves. Decreased POMC levels are also observed in peripheral nervous system tissue from diabetic patients. The antinociceptive pathway mediated by POMC is further impaired due to lysosomal degradation of μ-opioid receptor (MOR). Importantly, the neuropathic phenotype of the diabetic mice is rescued upon viral overexpression of POMC and MOR in the sensory ganglia. This study identifies an antinociceptive mechanism in the sensory ganglia that paves a way for a potential therapy for diabetic neuropathic pain.}, } @article {pmid33454875, year = {2021}, author = {Song, BI}, title = {A machine learning-based radiomics model for the prediction of axillary lymph-node metastasis in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {28}, number = {3}, pages = {664-671}, pmid = {33454875}, issn = {1880-4233}, support = {2019//Bisa Research Grant of Keimyung University/ ; }, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Fluorodeoxyglucose F18/administration & dosage ; Humans ; Lymphatic Metastasis/*diagnostic imaging/pathology ; *Machine Learning ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals/administration & dosage ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The aim of this study was to develop and validate machine learning-based radiomics model for predicting axillary lymph-node (ALN) metastasis in invasive ductal breast cancer (IDC) using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).

METHODS: A total of 100 consecutive IDC patients who underwent surgical resection of primary tumor with sentinel lymph-node biopsy and/or ALN dissection without any neoadjuvant treatment were analyzed. Volume of interests (VOIs) were drawn more than 2.5 of standardized uptake value in the primary tumor on the PET scan using 3D slicer. Pyradiomics package was used for the extraction of texture features in python. The radiomics prediction model for ALN metastasis was developed in 75 patients of the training cohort and validated in 25 patients of the test cohort. XGBoost algorithm was utilized to select features and build radiomics model. The sensitivity, specificity, and accuracy of the predictive model were calculated.

RESULTS: ALN metastasis was found in 43 patients (43%). The sensitivity, specificity, and accuracy of F-18 FDG PET/CT for the diagnosis of ALN metastasis in the entire patients were 55.8%, 93%, and 77%, respectively. The radiomics model for the prediction of ALN metastasis was successfully developed. The sensitivity, specificity, and accuracy of the radiomics model for the prediction of ALN metastasis in the test cohorts were 90.9%, 71.4%, and 80%, respectively.

CONCLUSION: The machine learning-based radiomics model showed good sensitivity for the prediction of ALN metastasis and could assist the preoperative individualized prediction of ALN status in patients with IDC.}, } @article {pmid33452367, year = {2021}, author = {Dortaj, H and Dolatyari, M and Zarghami, A and Alidoust, F and Rostami, A and Matloub, S and Yadipour, R}, title = {High-speed and high-precision PbSe/PbI2 solution process mid-infrared camera.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {1533}, pmid = {33452367}, issn = {2045-2322}, abstract = {Infrared (IR) cameras based on semiconductors grown by epitaxial methods face two main challenges, which are cost and operating at room temperature. The alternative new technologies which can tackle these two difficulties develop new and facile material and methods. Moreover, the implementation of high speed camera, which makes high resolution images with normal methods, is very expensive. In this paper, a new nanostructure based on a cost-effective solution processed technology for the implementation of the high-speed mid-infrared light camera at room temperature is proposed. To this end, the chemically synthesized PbSe-PbI2 core-shell Quantum Dots (QDs) are used. In this work, a camera including 10 × 10 pixels is fabricated and synthesized QDs spin-coated on interdigitated contact (IDC) and then the fabricated system passivated by epoxy resin. Finally, using an electronic reading circuit, all pixels are converted to an image on the monitor. To model the fabricated camera, we solved Schrodinger-Poisson equations self consistently. Then output current from each pixel is modeled based on semiconductor physics and dark and photocurrent, as well as Responsivity and Detectivity, are calculated. Then the fabricated device is examined, and dark and photocurrents are measured and compared to the theoretical results. The obtained results indicate that the obtained theoretical and measured experimental results are in good agreement together. The fabricated detector is high speed with a rise time of 100 ns. With this speed, we can get 10 million frames per second; this means we can get very high-resolution images. The speed of operation is examined experimentally using a chopper that modulates input light with 50, 100, 250, and 500 Hz. It is shown that the fabricated device operates well in these situations, and it is not limited by the speed of detector. Finally, for the demonstration of the proposed device operation, some pictures and movies taken by the camera are attached and inserted in the paper.}, } @article {pmid33449096, year = {2021}, author = {Sutton, EJ and Braunstein, LZ and El-Tamer, MB and Brogi, E and Hughes, M and Bryce, Y and Gluskin, JS and Powell, S and Woosley, A and Tadros, A and Sevilimedu, V and Martinez, DF and Toni, L and Smelianskaia, O and Nyman, CG and Razavi, P and Norton, L and Fung, MM and Sedorovich, JD and Sacchini, V and Morris, EA}, title = {Accuracy of Magnetic Resonance Imaging-Guided Biopsy to Verify Breast Cancer Pathologic Complete Response After Neoadjuvant Chemotherapy: A Nonrandomized Controlled Trial.}, journal = {JAMA network open}, volume = {4}, number = {1}, pages = {e2034045}, pmid = {33449096}, issn = {2574-3805}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Female ; Humans ; Image-Guided Biopsy/*methods ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Pilot Projects ; Predictive Value of Tests ; }, abstract = {IMPORTANCE: After neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) is an optimal outcome and a surrogate end point for improved disease-free and overall survival. To date, surgical resection remains the only reliable method for diagnosing pCR.

OBJECTIVE: To evaluate the accuracy of magnetic resonance imaging (MRI)-guided biopsy for diagnosing a pCR after NAC compared with reference-standard surgical resection.

Single-arm, phase 1, nonrandomized controlled trial in a single tertiary care cancer center from September 26, 2017, to July 29, 2019. The median follow-up was 1.26 years (interquartile range, 0.85-1.59 years). Data analysis was performed in November 2019. Eligible patients had (1) stage IA to IIIC biopsy-proven operable invasive breast cancer; (2) standard-of-care NAC; (3) MRI before and after NAC, with imaging complete response defined as no residual enhancement on post-NAC MRI; and (4) definitive surgery. Patients were excluded if they were younger than 18 years, had a medical reason precluding study participation, or had a prior history of breast cancer.

INTERVENTIONS: Post-NAC MRI-guided biopsy without the use of intravenous contrast of the tumor bed before definitive surgery.

MAIN OUTCOMES AND MEASURES: The primary end point was the negative predictive value of MRI-guided biopsy, with true-negative defined as negative results of the biopsy (ie, no residual cancer) corresponding to a surgical pCR. Accuracy, sensitivity, positive predictive value, and specificity were also calculated. Two clinical definitions of pCR were independently evaluated: definition 1 was no residual invasive cancer; definition 2, no residual invasive or in situ cancer.

RESULTS: Twenty of 23 patients (87%) had evaluable data (median [interquartile range] age, 51.5 [39.0-57.5] years; 20 women [100%]; 13 White patients [65%]). Of the 20 patients, pre-NAC median tumor size on MRI was 3.0 cm (interquartile range, 2.0-5.0 cm). Nineteen of 20 patients (95%) had invasive ductal carcinoma; 15 of 20 (75%) had stage II cancer; 11 of 20 (55%) had ERBB2 (formerly HER2 or HER2/neu)-positive cancer; and 6 of 20 (30%) had triple-negative cancer. Surgical pathology demonstrated a pCR in 13 of 20 (65%) patients and no pCR in 7 of 20 patients (35%) when pCR definition 1 was used. Results of MRI-guided biopsy had a negative predictive value of 92.8% (95% CI, 66.2%-99.8%), with accuracy of 95% (95% CI, 75.1%-99.9%), sensitivity of 85.8% (95% CI, 42.0%-99.6%), positive predictive value of 100%, and specificity of 100% for pCR definition 1. Only 1 patient had a false-negative MRI-guided biopsy result (surgical pathology showed <0.02 cm of residual invasive cancer).

CONCLUSIONS AND RELEVANCE: This study's results suggest that the accuracy of MRI-guided biopsy to diagnose a post-NAC pCR approaches that of reference-standard surgical resection. MRI-guided biopsy may be a viable alternative to surgical resection for this population after NAC, which supports the need for further investigation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03289195.}, } @article {pmid33447554, year = {2020}, author = {Zhang, C and Li, J and Jiang, H and Li, M}, title = {Use of fiberoductoscopy for the management of pathological nipple discharge: ten years follow up of a single center in China.}, journal = {Gland surgery}, volume = {9}, number = {6}, pages = {2035-2043}, pmid = {33447554}, issn = {2227-684X}, abstract = {BACKGROUND: Pathological nipple discharge (PND) is usually associated with benign intraductal papilloma, which has a higher malignant rate than other benign tumors in most cases. Fiberoductoscopy (FDS) is an alternative possibility in diagnostic and finding lesions in PND patients. Previously, the bloody discharge was presumed to show papilloma or breast cancer. However, as we started using FDS, papilloma or cancer also can be found in the cases with a transparent or yellow discharge. This study investigated the value of FDS for the diagnosis and locating of intraductal lesions in cases with nipple discharge.

METHODS: A retrospective analysis of 3,696 cases that initially presented with pathologic nipple discharge was performed. There were 4,456 FDSs performed, and the correlations between the FDS findings for distinct types of lesions and the pathological diagnosis were determined.

RESULTS: Among the 2,816 cases of elevated lesions, FDS confirmed 1,933 cases of intraductal papilloma, 584 cases of intraductal papillomatosis, and 299 cases of intraductal carcinoma. Among the 880 cases of non-elevated lesions, FDS confirmed 380 cases of duct dilation, 350 cases of duct inflammation, 136 cases of duct dilation and inflammation, and 14 cases of ductal carcinoma in situ (DCIS). All patients followed up 3 months to 12 years. There were 241 DCIS in total, and 8 cases had local recurrence, 2 cases had metastasis. Invasive ductal carcinoma, 41 cases, 3 had recurrence and 3 had metastases, and 1 for death. Invasive lobular carcinoma 23 cases, recurrence 2 cases, metastasis 1 case.

CONCLUSIONS: FDS has a high positive predictive rate and correlates well with the results of the pathological examination. The advantage of FDS is that it can observe the lesions, increasing the detection rate of early stage breast cancer, simple to operate, low cost, and no need for the appointment, appropriate for Chinese conditions.}, } @article {pmid33447551, year = {2020}, author = {Wang, L and Yang, W and Xie, X and Liu, W and Wang, H and Shen, J and Ding, Y and Zhang, B and Song, B}, title = {Application of digital mammography-based radiomics in the differentiation of benign and malignant round-like breast tumors and the prediction of molecular subtypes.}, journal = {Gland surgery}, volume = {9}, number = {6}, pages = {2005-2016}, pmid = {33447551}, issn = {2227-684X}, abstract = {BACKGROUND: This study aimed to investigate the diagnostic performance of radiomic features based on digital mammography (DM) in the differential diagnosis of benign and malignant round-like (round and oval) solid tumors with circumscribed or obscured margins but without suspicious malignant or benign macrocalcifications and to investigate whether quantitative radiomic features can distinguish triple-negative breast cancer (TNBC) from non-TNBC (NTNBC).

METHODS: This retrospective study included 112 patients with round-like tumors who underwent DM within 20 days preoperatively. Breast masses were segmented manually on the DM images, then radiomic features were extracted. The predictive models were used to distinguish between benign and malignant tumors and to predict TNBC in invasive ductal carcinoma. The receiver operating characteristic curves (ROCs) for these models were obtained for initial DM characteristics, radiomic features to predict malignant tumors and TNBC. The decision curve was obtained to evaluate the clinical usefulness of the model for the prediction of benign or malignant tumors.

RESULTS: The study cohort included 79 patients with pathologically confirmed malignant masses and 33 patients with benign (training cohort: n=79; testing cohort: n=33). A total of 396 features were extracted from the DM images for each patient. The radiomics model for the prediction of malignant tumors achieved an area under the receiver operating characteristic curve (AUC) of 0.88 [95% confidence interval (CI), 0.76-1.00] in the testing cohort; the radiomics model for the prediction of TNBC achieved an AUC of 0.84 (95% CI, 0.73-0.96). In contrast, DM characteristics alone poorly predicted malignant tumors, with the density achieving an AUC 0.69 (95% CI, 0.59-0.79); there was no significant difference in DM characteristics between TNBC and NTNBC (P>0.05, all). The decision curve showed the good clinical usefulness of the model for the prediction of malignant tumors.

CONCLUSIONS: This study showed that DM-based radiomics can accurately discriminate between benign and malignant round-like tumors with circumscribed or obscured margins but without suspicious malignant or benign macrocalcifications. Additionally, it can be used to predict TNBC in invasive ductal carcinoma. DM-based radiomics can aid radiologists in mammogram reading, clinical diagnosis and decision-making.}, } @article {pmid33445940, year = {2020}, author = {Bartovská, Z and Andrle, F and Beran, O and Zlámal, M and Řezáč, D and Murinova, I and Holub, M}, title = {Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {69}, number = {4}, pages = {164-171}, pmid = {33445940}, issn = {1210-7913}, mesh = {COVID-19/diagnosis/*epidemiology/therapy ; Czech Republic/epidemiology ; Female ; Hospitals, Military ; Humans ; Male ; Middle Aged ; Retrospective Studies ; United States ; }, abstract = {AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature.

PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results.  These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software.

RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc).

CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.}, } @article {pmid33443130, year = {2021}, author = {Trinh, A and Gil Del Alcazar, CR and Shukla, SA and Chin, K and Chang, YH and Thibault, G and Eng, J and Jovanović, B and Aldaz, CM and Park, SY and Jeong, J and Wu, C and Gray, J and Polyak, K}, title = {Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {4}, pages = {623-635}, pmid = {33443130}, issn = {1557-3125}, support = {R35 CA197623/CA/NCI NIH HHS/United States ; U01 CA195469/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; U24 CA224331/CA/NCI NIH HHS/United States ; R50 CA211482/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*immunology ; Carcinoma, Ductal, Breast/*genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*immunology ; Female ; Genomics ; Humans ; Immune System ; }, abstract = {The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions. Immune "hot" and "cold" tumors can arise as early as DCIS and are subtype-specific. Topologic analysis showed a similar degree of pan-leukocyte-tumor mixing in both DCIS and IDC but differ when assessing specific immune subpopulations such as CD4 T cells and CD68 macrophages. Tumor-specific copy-number aberrations in MHC-I presentation machinery and losses in 3p, 4q, and 5p are associated with differences in immune signaling in estrogen receptor (ER)-negative IDC. Common oncogenic hotspot mutations in genes including TP53 and PIK3CA are predicted to be neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition, and are associated with differences in immune signaling. We highlight both tumor and immune-specific changes in the transition of pure DCIS to IDC, including genetic changes in tumor cells that may have a role in modulating immune function and assist in immune escape, driving the transition to IDC. IMPLICATIONS: We demonstrate that the in situ to IDC evolutionary bottleneck is shaped by both tumor and immune cells.}, } @article {pmid33440156, year = {2021}, author = {Schlein, C and Fischer, AW and Sass, F and Worthmann, A and Tödter, K and Jaeckstein, MY and Behrens, J and Lynes, MD and Kiebish, MA and Narain, NR and Bussberg, V and Darkwah, A and Jespersen, NZ and Nielsen, S and Scheele, C and Schweizer, M and Braren, I and Bartelt, A and Tseng, YH and Heeren, J and Scheja, L}, title = {Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution.}, journal = {Cell reports}, volume = {34}, number = {2}, pages = {108624}, pmid = {33440156}, issn = {2211-1247}, support = {F32 DK102320/DK/NIDDK NIH HHS/United States ; K01 DK111714/DK/NIDDK NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue, Brown/*metabolism ; Animals ; Fatty Acids/*biosynthesis ; Humans ; Mice ; }, abstract = {Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans.}, } @article {pmid33437736, year = {2020}, author = {Abdolahi, M and Salehi, M and Shokatian, I and Reiazi, R}, title = {Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {34}, number = {}, pages = {140}, pmid = {33437736}, issn = {1016-1430}, abstract = {Background: Breast cancer is one of the most causes of death in women. Early diagnosis and detection of Invasive Ductal Carcinoma (IDC) is an important key for the treatment of IDC. Computer-aided approaches have great potential to improve diagnosis accuracy. In this paper, we proposed a deep learning-based method for the automatic classification of IDC in whole slide images (WSI) of breast cancer. Furthermore, different types of deep neural networks training such as training from scratch and transfer learning to classify IDC were evaluated. Methods: In total, 277524 image patches with 50×50-pixel size form original images were used for model training. In the first method, we train a simple convolutional neural network (named it baseline model) on these images. In the second approach, we used the pre-trained VGG-16 CNN model via feature extraction and fine-tuning for the classification of breast pathology images. Results: Our baseline model achieved a better result for the automatic classification of IDC in terms of F-measure and accuracy (83%, 85%) in comparison with original paper on this data set and achieved a comparable result with a new study that introduced accepted-rejected pooling layer. Also, transfer learning via feature extraction yielded better results (81%, 81%) in comparison with handcrafted features. Furthermore, transfer learning via feature extraction yielded better classification results in comparison with the baseline model. Conclusion: The experimental results demonstrate that using deep learning approaches yielded better results in comparison with handcrafted features. Also, using transfer learning in histopathology image analysis yielded significant results in comparison with training from scratch in much less time.}, } @article {pmid33433431, year = {2021}, author = {Xia, Y and Liu, X and Li, W and Zhu, Y}, title = {Potential role of significant GATA3 mutation in male breast cancer responding to endocrine therapy: A case report.}, journal = {Indian journal of pathology & microbiology}, volume = {64}, number = {1}, pages = {161-164}, doi = {10.4103/IJPM.IJPM_160_19}, pmid = {33433431}, issn = {0974-5130}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast/pathology ; Breast Neoplasms, Male/diagnostic imaging/*drug therapy/*genetics/secondary ; Endocrine System/drug effects ; GATA3 Transcription Factor/*genetics ; Humans ; Male ; Middle Aged ; *Mutation ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.}, } @article {pmid33433407, year = {2021}, author = {Farrag, MS and Anter, AH and Farrag, NS and Ibrahiem, AT}, title = {"Switch of E-Cadherin to N-Cadherin expression in different molecular subtypes of breast invasive duct carcinomas and its correlation with clinicopathological features".}, journal = {Indian journal of pathology & microbiology}, volume = {64}, number = {1}, pages = {38-46}, doi = {10.4103/IJPM.IJPM_924_19}, pmid = {33433407}, issn = {0974-5130}, mesh = {Antigens, CD/*genetics ; Biomarkers, Tumor ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/classification/*genetics/*pathology/secondary ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paraffin Embedding ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma.

MATERIALS AND METHODS: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57).

CONCLUSIONS/SIGNIFICANCE: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.}, } @article {pmid33432595, year = {2021}, author = {Abraham, E and Zagoory-Sharon, O and Feldman, R}, title = {Early maternal and paternal caregiving moderates the links between preschoolers' reactivity and regulation and maturation of the HPA-immune axis.}, journal = {Developmental psychobiology}, volume = {63}, number = {5}, pages = {1482-1498}, doi = {10.1002/dev.22089}, pmid = {33432595}, issn = {1098-2302}, mesh = {Child ; Child, Preschool ; Fathers/psychology ; Female ; Humans ; Hypothalamo-Hypophyseal System ; Infant ; Male ; Parenting/psychology ; *Pituitary-Adrenal System ; *Saliva ; }, abstract = {While early caregiving and child's temperamental dispositions work in concert to shape social-emotional outcomes, their unique and joint contribution to the maturation of the child's stress and immune systems remain unclear. We followed children longitudinally from infancy to preschool to address the buffering effect of early parenting on the link between temperamental dysregulation and hypothalamic-pituitary-adrenal (HPA)-immune axis in preschool-aged children. Participants included 47 typically developing children and their 94 parents in both mother-father and two-father families followed across the first 4-years of family formation. In infancy, we observed parent-infant synchrony and measured parental oxytocin; in preschool, we observed temperamental reactivity and self-regulation and assessed children's cortisol and secretory Immunoglobulin A (s-IgA), biomarkers of the stress and immune systems. Greater self-regulation and lower negative emotionality were associated with lower baseline s-IgA and cortisol, respectively. However, these links were defined by interactive effects so that preschoolers with low self-regulation displayed higher s-IgA levels only in cases of low parent-infant synchrony and negative emotionality linked with greater baseline cortisol levels only when parental oxytocin levels were low. Results emphasize the long-term stress-buffering role of the neurobiology of parental care, demonstrate comparable developmental paths for mothers and fathers, and delineate the complex developmental cascades to the maturation of children's stress-management systems.}, } @article {pmid33429799, year = {2021}, author = {Karatas, M and Zengel, B and Durusoy, R and Tasli, F and Adibelli, Z and Simsek, C and Uslu, A}, title = {Clinicopathologic features of single bone metastasis in breast cancer.}, journal = {Medicine}, volume = {100}, number = {1}, pages = {e24164}, pmid = {33429799}, issn = {1536-5964}, mesh = {Adult ; Aged ; Bone Neoplasms/*classification/pathology ; Bone and Bones/*pathology/physiopathology ; Breast Neoplasms/*complications ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis/*physiopathology ; }, abstract = {The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.}, } @article {pmid33428505, year = {2021}, author = {Nevagi, RJ and Good, MF and Stanisic, DI}, title = {Plasmodium infection and drug cure for malaria vaccine development.}, journal = {Expert review of vaccines}, volume = {20}, number = {2}, pages = {163-183}, doi = {10.1080/14760584.2021.1874923}, pmid = {33428505}, issn = {1744-8395}, mesh = {Animals ; Antigens, Protozoan/immunology ; Antimalarials/administration & dosage ; Humans ; Malaria/immunology/parasitology/*prevention & control ; Malaria Vaccines/*administration & dosage/immunology ; Plasmodium/*immunology/parasitology ; }, abstract = {Introduction: Despite decades of research into the development of a vaccine to combat the malaria parasite, a highly efficacious malaria vaccine is not yet available. Different whole parasite-based vaccine approaches, including deliberate Plasmodium infection and drug cure (IDC), have been evaluated in pre-clinical and early phase clinical trials. The advantage of whole parasite vaccines is that they induce immune responses against multiple parasite antigens, thus lowering the impact of antigenic diversity. Deliberate Plasmodium IDC, as a vaccine approach, involves administering infectious, live parasites in combination with an anti-malarial drug, which controls the infection and enables induction of protective immune responses.}, } @article {pmid33425023, year = {2020}, author = {Zhang, H and Zhang, N and Li, Y and Liang, Y and Yang, Q}, title = {Evaluation of efficacy of chemotherapy for mucinous carcinoma: a surveillance, epidemiology, and end results cohort study.}, journal = {Therapeutic advances in medical oncology}, volume = {12}, number = {}, pages = {1758835920975603}, pmid = {33425023}, issn = {1758-8340}, abstract = {BACKGROUND: In this study, we investigated the impact of chemotherapy on breast cancer-specific survival (BCSS) in patients with mucinous carcinoma using the surveillance, epidemiology, and end results (SEER) database.

METHODS: A large-scale SEER-based retrospective analysis was conducted; 13,329 patients with mucinous carcinoma from 1994 to 2014 were identified. Clinicopathological characteristics were compared using the chi-square test. BCSS curves were generated using the Kaplan-Meier method. The prognostic significance of all demographic and clinicopathological characteristics and treatment patterns were calculated using univariate and multivariate regression analyses.

RESULTS: Mucinous carcinoma was demonstrated to be less aggressive than invasive ductal carcinoma and predicted a better prognosis in the Kaplan-Meier analysis (hazard ratios = 0.336, 95% confidence interval: 0.308-0.368, p < 0.001). Univariate and multivariate analyses revealed that chemotherapy did not provide any additional benefit for patients with mucinous carcinoma. Predictors for receiving chemotherapy were younger age, estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-positive status, higher grade, larger tumor size, lymph node involvement, radiation reception, and mastectomy. Further subgroup analysis verified that regardless of the hormone receptor (HR) and lymph node (LN) status, patients did not benefit from chemotherapy.

CONCLUSION: Our study showed that patients with HR+/LN- mucinous carcinoma did not benefit from chemotherapy and that chemotherapy could not improve the survival of all subtypes of mucinous carcinoma based on large-scale SEER data. These results support that patients with mucinous carcinoma could be exempt from chemotherapy. Additional research is needed to further evaluate the impact of adjuvant treatments, particularly in patients with favorable histology.}, } @article {pmid33422900, year = {2021}, author = {Huang, K and Appiah, L and Mishra, A and Bagaria, SP and Gabriel, ME and Misra, S}, title = {Clinicopathologic Characteristics and Prognosis of Invasive Papillary Carcinoma of the Breast.}, journal = {The Journal of surgical research}, volume = {261}, number = {}, pages = {105-112}, doi = {10.1016/j.jss.2020.12.026}, pmid = {33422900}, issn = {1095-8673}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*pathology ; Breast Neoplasms/diagnosis/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*mortality/pathology/therapy ; Carcinoma, Papillary/diagnosis/*mortality/pathology/therapy ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; United States/epidemiology ; }, abstract = {BACKGROUND: Invasive papillary carcinoma (IPC) of the breast is thought to carry a more favorable prognosis than invasive ductal carcinoma (IDC). The aim of this study is to investigate the clinicopathological characteristics between IPC and IDC and their prognosis using a large nationwide data set.

METHODS: Female patients diagnosed with malignant IPC and IDC between 2005 and 2014 were analyzed. Patients with incomplete survival data, stage 0/IV, unknown stage, or recurrent disease were excluded. Five-year overall survival was compared between IPC and IDC.

RESULTS: Among 308,426 patients, 1147 had IPC and 307,279 had IDC. IPC presented more in older postmenopausal women, black Americans, and people who had government insurance. IPC had larger tumor size, lower-grade, and earlier-stage disease, less node-positive disease, higher hormone positivity, and lower human epidermal growth factor receptor 2 amplification. Adjuvant radiation and chemotherapy rates were lower in IPC than those in IDC. IPC had a similar 5-year overall survival as compared with IDC overall (86.8% versus 88.7%) (P = 0.06). Age, pathologic stage, and radiation treatment were shown to be independent prognostic factors of IPC.

CONCLUSIONS: IPC has a similar prognosis as IDC, suggesting that these patients should follow the same treatment protocols.}, } @article {pmid33421821, year = {2021}, author = {Hoshina, H and Takei, H and Sakatani, T and Naito, Z}, title = {CDX2-positive breast cancer presented with axillary lymph node metastases: A case report.}, journal = {Cancer treatment and research communications}, volume = {26}, number = {}, pages = {100300}, doi = {10.1016/j.ctarc.2020.100300}, pmid = {33421821}, issn = {2468-2942}, mesh = {Axilla ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/therapy ; CDX2 Transcription Factor/analysis/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Ultrasonography ; }, abstract = {BACKGROUND: The caudal type homeobox 2 transcription factor (CDX2) is a specific and sensitive marker for intestinal carcinoma, but usually not expressed in breast cancer. In CDX2-positive metastatic cancer of occult primary, the origin is highly suspicious of an enteric carcinoma.

CASE PRESENTATION: A 50-year-old woman complained of enlarged lymph nodes (LNs) in the right axilla. Mammography and ultrasonography scans showed no abnormal findings in her breasts. Core needle biopsy (CNB) revealed metastatic adenocarcinoma. Immunohistochemical staining was positive for CDX2 intensely. The primary tumor was suspicious of intestinal adenocarcinoma. A dynamic contrast-enhanced magnetic resonance imaging scan revealed an accentuated lesion which was detected using a second-look ultrasound, and diagnosed invasive ductal carcinoma by CNB. A partial mastectomy of the right breast with level I and II axillary LN dissection was performed. A few cells of primary cancer were expressed CDX2 and estrogen receptor. The final pathological diagnosis was T1bN3aM0 stage IIIC. The fluorescent double staining showed that CDX2 simultaneously expressed on the Ki67 positive cells of metastatic tumors. The adjuvant treatment included chemotherapy and radiation, followed by tamoxifen administration. The patient survived without any recurrences over the following 36 months.

CONCLUSIONS: We report a rare case of CDX2-positive metastatic breast cancer in the axillary LNs. As some literatures reported vitamin D pathways induced cancer cell apoptosis and inhibition, these metastatic cells of our case might play the effort of autoregulation of inhibiting progression.}, } @article {pmid33419057, year = {2021}, author = {Lopes, BC and Braga, CZ and Ventura, FV and de Oliveira, JG and Kato-Junior, EM and Bordin-Junior, NA and Zuccari, DAPC}, title = {miR-210 and miR-152 as Biomarkers by Liquid Biopsy in Invasive Ductal Carcinoma.}, journal = {Journal of personalized medicine}, volume = {11}, number = {1}, pages = {}, pmid = {33419057}, issn = {2075-4426}, support = {2017/11807-3//Fundação de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)/ ; 2017/15006-5//Fundação de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)/ ; 028/2018//Fundação de Apoio à Pesquisa e Extensão de Sao Jose do Rio Preto (FAPERP)/ ; }, abstract = {UNLABELLED: Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis.

METHODS: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins.

RESULTS: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel-Lindau (VHL) protein expression was observed.

CONCLUSIONS: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging.}, } @article {pmid33417752, year = {2020}, author = {Téllez-Duarte, A and González-Ramírez, LV}, title = {[COVID-19 in orthopedics].}, journal = {Acta ortopedica mexicana}, volume = {34}, number = {3}, pages = {153-157}, pmid = {33417752}, issn = {2306-4102}, mesh = {*COVID-19 ; Humans ; *Orthopedic Procedures ; *Orthopedics ; SARS-CoV-2 ; }, abstract = {STUDY DESIGN: This is a systematic literature review for COVID-19, SARS-CoV-2 with Orthopedic and Spine Surgery relevance.

OBJECTIVES: It is to determine in Orthopedic surgery and Spine Surgery and its branches the new required safety protocols when attending patients with risk of infection, or transmission for COVID-19 and comorbidities in the outpatient and inpatient hospital setting.

METHODS: A systematic literature review.

RESULTS: Recent knowledge for this disease has changed the Virus affects ORF-8 protein of the Hemoglobin destroying B-Hemoglobin, and IDC (intravascular disseminated coagulation) is found to happen in many patients, together with its capsular capability to adhere to metallic and plastic surfaces, pneumonic pattern associated with ventilator use, and the relapse in some patients, changes the view, preventative measures and treatment of this disease. Publication of global statistics show that patients with hypertension tend to have a higher rate of suffering the disease. Some new measures are proposed.

CONCLUSIONS: New care guidelines for COVID-19 patients are proposed based on the new research on SARS-CoV-2 clinical pathologic findings are necessary.}, } @article {pmid33416185, year = {2021}, author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD}, title = {miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {45}, number = {2}, pages = {706-716}, pmid = {33416185}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology/surgery ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/mortality/secondary/surgery ; Cell Line, Tumor ; DNA-Binding Proteins/*genetics ; Disease Progression ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mastectomy ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasm Recurrence, Local/*epidemiology/genetics ; RNA-Binding Proteins/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {MicroRNA (miRNA/mir)‑490‑3p has been defined as a tumor suppressor in different types of cancer, including breast cancer. However, miR‑490‑3p has been shown to function as a tumor suppressor and promoter in a context‑dependent manner in hepatocellular and lung cancer. Contrary to previous studies, the present study revealed that miR‑490‑3p expression was significantly higher in invasive ductal carcinoma (IDC) tissue specimens, the most common form of breast cancer, compared to tumor‑adjacent normal tissue specimens (n=20). Its expression was also higher in the more metastatic breast cancer cell line, MDA‑MB‑231, compared to the non‑metastatic breast cancer cell line, MCF7, and the moderately metastatic breast cancer cell line, MDA‑MB‑468. The expression of miR‑490‑3p was induced following transforming growth factor (TGF)‑β‑induced epithelial‑to‑mesenchymal transition (EMT) in MCF10A cells. Gain‑and loss‑of‑function assays revealed that the expression of miR‑490‑3p regulated the proliferation, colony formation, EMT, migration and invasion in vitro, but not the apoptosis of MDA‑MB‑468 and MDA‑MB‑231 cells. The knockdown of miR‑490‑3p expression in MDA‑MB‑231 cells inhibited experimental metastasis in a tumor xenograft assay. As in lung cancer, miR‑490‑3p was found to target and downregulate the expression of the tumor suppressor RNA binding protein poly r(C) binding protein 1 (PCBP1). PCBP1 protein and miR‑490‑3p expression inversely correlated in patients with ductal carcinoma in situ (DCIS; n=10; no nodal involvement) and IDC (n=10; different stages of metastatic progression) with a significantly higher miR‑490‑3p expression in patients with IDC compared to those with DCIS. The expression of miR‑490‑3p was negatively associated with both overall and disease‑free survival in the patients with breast cancer included in the present study. On the whole, the results confirm a pro‑metastatic role of miR‑490‑3p in IDC, establishing it as a biomarker for disease progression in these patients.}, } @article {pmid33415472, year = {2022}, author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M}, title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.}, journal = {European child & adolescent psychiatry}, volume = {31}, number = {4}, pages = {637-648}, pmid = {33415472}, issn = {1435-165X}, mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; }, abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).}, } @article {pmid33415073, year = {2020}, author = {Yang, C and Lei, C and Zhang, Y and Zhang, J and Ji, F and Pan, W and Zhang, L and Gao, H and Yang, M and Li, J and Wang, K}, title = {Comparison of Overall Survival Between Invasive Lobular Breast Carcinoma and Invasive Ductal Breast Carcinoma: A Propensity Score Matching Study Based on SEER Database.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {590643}, pmid = {33415073}, issn = {2234-943X}, abstract = {OBJECTIVE: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most breast cancers. However, the overall survival (OS) differences between ILC and IDC remain controversial. This study aimed to compare nonmetastatic ILC to IDC in terms of survival and prognostic factors for ILC.

METHODS: This retrospective cohort study used data from the Surveillance, Epidemiology and End Results (SEER) Cancer Database (www.seer.cancer.gov). Women diagnosed with nonmetastatic ILC and IDC between 2006 and 2016 were included. A propensity score matching (PSM) method was used in our analysis to reduce baseline differences in clinicopathological characteristics and survival outcomes. Kaplan-Meier curves and log-rank test were used for survival analysis.

RESULTS: Compared to IDC patients, ILC patients were diagnosed later in life with poorly differentiated and larger lesions, as well as increased expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). A lower rate of radiation therapy and chemotherapy was observed in ILC. After PSM, ILC, and IDC patients exhibited similar OS (HR=1.017, p=0.409, 95% CI: 0.967-1.069). In subgroup analysis of HR-negative, AJCC stage III, N2/N3 stage patients, or those who received radiotherapy, ILC patients exhibited worse OS compared to IDC patients. Furthermore, multivariate analysis revealed a 47% survival benefit for IDC compared to ILC in HR-negative patients who received chemotherapy (HR=1.47, p=0.01, 95% CI: 1.09-1.97).

CONCLUSIONS: Our results demonstrated that ILC and IDC patients had similar OS after PSM. However, ILC patients with high risk indicators had worse OS compared to IDC patients by subgroup analysis.}, } @article {pmid33413755, year = {2020}, author = {Zeng, XQ and Jiang, SS and Peng, YY and Liu, MF and Ye, CS and Dong, JY}, title = {Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.}, journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih}, volume = {35}, number = {4}, pages = {377-382}, doi = {10.24920/003799}, pmid = {33413755}, issn = {1001-9294}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Platelet Count ; Thrombocytopenia/blood/*chemically induced/drug therapy ; Trastuzumab/*adverse effects ; }, abstract = {We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×10[9]/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.}, } @article {pmid33412491, year = {2021}, author = {Mayopoulos, GA and Ein-Dor, T and Dishy, GA and Nandru, R and Chan, SJ and Hanley, LE and Kaimal, AJ and Dekel, S}, title = {COVID-19 is associated with traumatic childbirth and subsequent mother-infant bonding problems.}, journal = {Journal of affective disorders}, volume = {282}, number = {}, pages = {122-125}, pmid = {33412491}, issn = {1573-2517}, support = {R21 HD100817/HD/NICHD NIH HHS/United States ; }, mesh = {*COVID-19 ; Female ; Humans ; Infant ; Mothers ; Parturition ; Pregnancy ; Retrospective Studies ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic/epidemiology ; }, abstract = {BACKGROUND: Knowledge of women's experience of childbirth in the outbreak of the coronavirus (COVID-19) pandemic and associated maternal health outcomes is scarce.

METHODS: A sample of primarily American women who gave birth around the height of COVID-19 (n = 1,611) and matched controls, i.e., women who gave birth before COVID-19 (n = 640), completed an anonymous Internet survey about recent childbirth, birth-related traumatic stress (peritraumatic distress inventory; PTSD-checklist), maternal bonding (maternal attachment inventory; mother-to-infant bonding scale) and breastfeeding status. Groups (n = 637 in each) were matched on demographics, prior mental health/trauma and childbirth factors to determine the unique contribution of COVID-19 to the psychological experience of childbirth.

RESULTS: Mothers in COVID-19-exposed communities endorsed more clinically acute stress response to childbirth than matched controls (Z = 2.65, p = .008, OR= 1.38). A path mediation model revealed that acute stress mediated the relationship between study group and postpartum outcomes. Specifically, higher acute stress response in birth was associated with more childbirth-related posttraumatic stress disorder symptoms (β = .42, p < .001) and less bonding with the infant (β = .26, p < .001), including breastfeeding problems (β = .10, p < .01).

LIMITATIONS: Use of a convenient internet sample introduces bias towards more educated women and reliance on retrospective self-report assessments may entail recall bias.

CONCLUSIONS: COVID-19 is a major stressor for delivering women. It can heighten traumatic childbirth experiences and interfere with successful postpartum adjustment. Clinical attention to traumatic stress in childbirth and problems with caring for the young during this pandemic is important.}, } @article {pmid33409705, year = {2021}, author = {Ohara, M and Koi, Y and Sasada, T and Kajitani, K and Mizuno, S and Takata, A and Okamoto, A and Nagata, I and Sumita, M and Imachi, K and Watanabe, M and Daimaru, Y and Kawamura, S}, title = {Spontaneous regression of breast cancer with immune response: a case report.}, journal = {Surgical case reports}, volume = {7}, number = {1}, pages = {10}, pmid = {33409705}, issn = {2198-7793}, abstract = {BACKGROUND: Spontaneous regression (SR) is a rare phenomenon in which a cancer disappears or remits without treatment. We report a case of breast cancer that showed spontaneous tumor regression in the surgical specimen after core needle biopsy.

CASE PRESENTATION: A 59-year-old woman came to our hospital complaining of a painful lump in the right breast. In the upper-outer quadrant of the right breast, a tumor with an unclear boundary, 30 mm in diameter, was palpable. In pathological findings from needle biopsy, the tumor was diagnosed as solid-type invasive ductal breast carcinoma. Partial coagulation necrosis was generated in estrogen receptor-negative, HER2-negative, and AE1/AE3-positive ductal carcinoma without infiltration of lymphocytes. Surgery for right breast cancer was then performed. Histological examination of the surgical specimen revealed the tumor was invasive ductal carcinoma with lymphocyte infiltration, coagulation necrosis, and fibrous tissue with hemosiderin. The tumor formed a solid nest, 3 mm in diameter, suggesting the possibility of SR.

CONCLUSIONS: Immune responses, infection, hormones, surgical stress, and ischemia have been reported as mechanisms of SR. The findings in this case strongly suggest that SR of breast cancer is associated with anti-tumor immune responses.}, } @article {pmid33409083, year = {2020}, author = {Sinduja, R and Kumaran, R and Sundaramurthi, S and Krishnaraj, B and Sistla, SC}, title = {Carcinoma of the Accessory Axillary Breast: A Diagnostic Dilemma and a Management Challenge.}, journal = {Cureus}, volume = {12}, number = {12}, pages = {e11844}, pmid = {33409083}, issn = {2168-8184}, abstract = {Carcinoma of the accessory axillary breast is uncommon, with an incidence of 0.2 to 0.6%. We report a patient whose biopsy of a suspicious lesion in the axilla present for one year revealed invasive ductal carcinoma (IDC). There was presence of breast tissue and absence of lymphoid tissue in the biopsy, suggesting a breast malignancy. Magnetic resonance mammography was suggestive of the lesion well away from the normal breast, confirming an accessory axillary breast. She was offered wide local excision of the lesion with axillary lymph node dissection and modified radical mastectomy (MRM), and she chose the latter. Her post-operative biopsy showed the involvement of all the 25 lymph nodes harvested. Any suspicious lesion in the axilla should be promptly worked up for malignancy. Accessory axillary breast carcinoma, if confirmed, can be addressed with wide local excision along with axillary lymph node dissection. However, further studies should clarify this and the outcomes.}, } @article {pmid33408892, year = {2020}, author = {Lee, YJ and Shin, J and Jung, JM and Kim, EK and Jung, J and Jeong, JH and Gong, G and Ko, B}, title = {Bilateral Metachronous Paget's Disease of the Accessory Breasts in a Male.}, journal = {Journal of breast cancer}, volume = {23}, number = {6}, pages = {665-671}, pmid = {33408892}, issn = {1738-6756}, abstract = {Bilateral axillary Paget's disease in men is a rare occurrence with limited reports on its diagnosis, treatment, and prognosis. Here, we report the case of a 55-year-old Korean male, who presented with a palpable mass and eczematous skin lesion on the left axilla. An incisional biopsy and histopathologic examination indicated invasive ductal carcinoma with Paget's disease arising in the accessory breast. Magnetic resonance imaging and positron emission tomography revealed no malignancy in the normal breast and other organs. The patient was subjected to a wide excision, wherein the left axillary lymph node was dissected, followed by the administration of adjuvant chemotherapy and radiation therapy. After 17 months of disease-free survival, the patient was diagnosed with Paget's disease of the contralateral accessory breast. He underwent wide excision surgery along with radiation therapy. To the best of our knowledge, this is the first report of bilateral extramammary Paget's disease in a male.}, } @article {pmid33407746, year = {2021}, author = {Yamashita, M and Kamei, Y and Murakami, A and Ozaki, E and Okujima, K and Takemoto, K and Takaoka, M and Tsukamoto, D and Kusakabe, E and Shidahara, T and Noda, H and Aoki, R and Taguchi, K and Nishiyama, K and Eguchi, M and Takada, Y}, title = {Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review.}, journal = {Hereditary cancer in clinical practice}, volume = {19}, number = {1}, pages = {3}, pmid = {33407746}, issn = {1731-2302}, support = {19K16715//JSPS KAKENHI/ ; }, abstract = {BACKGROUND: Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia.

CASE PRESENTATION: A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery.

CONCLUSIONS: There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.}, } @article {pmid33402291, year = {2021}, author = {Mnejja, M and Kallel, S and Thabet, W and Regaieg, M and Kallel, R and Boudawara, T and Daoud, J and Hammami, B and Charfeddine, I}, title = {[Ductal carcinomas of the parotid gland].}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {25}, number = {2}, pages = {155-160}, doi = {10.1016/j.canrad.2020.06.034}, pmid = {33402291}, issn = {1769-6658}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology/secondary/*surgery ; Carcinoma, Ductal, Breast/pathology/secondary ; Facial Nerve/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neck Dissection/statistics & numerical data ; Neoplasm Invasiveness ; Parotid Gland/diagnostic imaging/surgery ; Parotid Neoplasms/diagnostic imaging/pathology/secondary/*surgery ; Prognosis ; Retrospective Studies ; Skin Neoplasms/pathology ; }, abstract = {PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland.

MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed.

RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression.

CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.}, } @article {pmid33401758, year = {2021}, author = {Mohr, H and Ballke, S and Bechmann, N and Gulde, S and Malekzadeh-Najafabadi, J and Peitzsch, M and Ntziachristos, V and Steiger, K and Wiedemann, T and Pellegata, NS}, title = {Mutation of the Cell Cycle Regulator p27kip1 Drives Pseudohypoxic Pheochromocytoma Development.}, journal = {Cancers}, volume = {13}, number = {1}, pages = {}, pmid = {33401758}, issn = {2072-6694}, support = {CRC/Transregio 205/1, Project B11, B12 and S01 "The Adrenal: Central Relay in Health and Disease"//Deutsche Forschungsgemeinschaft/ ; CRC 824 "Imaging for Selection, Monitoring and Individualization of Cancer Therapies", Project B8, A1/Z3 and Z2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Pseudohypoxic tumors activate pro-oncogenic pathways typically associated with severe hypoxia even when sufficient oxygen is present, leading to highly aggressive tumors. Prime examples are pseudohypoxic pheochromocytomas and paragangliomas (p-PPGLs), neuroendendocrine tumors currently lacking effective therapy. Previous attempts to generate mouse models for p-PPGLs all failed. Here, we describe that the rat MENX line, carrying a Cdkn1b (p27) frameshift-mutation, spontaneously develops pseudohypoxic pheochromocytoma (p-PCC).

METHODS: We compared rat p-PCCs with their cognate human tumors at different levels: histology, immunohistochemistry, catecholamine profiling, electron microscopy, transcriptome and metabolome. The vessel architecture and angiogenic potential of pheochromocytomas (PCCs) was analyzed by light-sheet fluorescence microscopy ex vivo and multi-spectral optoacoustic tomography (MSOT) in vivo.

RESULTS: The analysis of tissues at various stages, from hyperplasia to advanced grades, allowed us to correlate tumor characteristics with progression. Pathological changes affecting the mitochrondrial ultrastructure where present already in hyperplasias. Rat PCCs secreted high levels of norepinephrine and dopamine. Transcriptomic and metabolomic analysis revealed changes in oxidative phosphorylation that aggravated over time, leading to an accumulation of the oncometabolite 2-hydroxyglutarate, and to hypermethylation, evident by the loss of the epigenetic mark 5-hmC. While rat PCC xenografts showed high oxygenation, induced by massive neoangiogenesis, rat primary PCC transcriptomes possessed a pseudohypoxic signature of high Hif2a, Vegfa, and low Pnmt expression, thereby clustering with human p-PPGL.

CONCLUSION: Endogenous rat PCCs recapitulate key phenotypic features of human p-PPGLs. Thus, MENX rats emerge as the best available animal model of these aggressive tumors. Our study provides evidence of a link between cell cycle dysregulation and pseudohypoxia.}, } @article {pmid33400149, year = {2021}, author = {Has Simsek, D and Isik, EG and Engin, MN and Kuyumcu, S and Mudun, A and Sanli, Y}, title = {Somatostatin receptor-positive breast lesions on [68]Ga-DOTATATE PET/CT.}, journal = {Annals of nuclear medicine}, volume = {35}, number = {2}, pages = {270-277}, pmid = {33400149}, issn = {1864-6433}, mesh = {Adolescent ; Adult ; Breast/*diagnostic imaging ; Female ; Fibroadenoma/diagnostic imaging ; Gallium Radioisotopes/*chemistry ; Humans ; Image Processing, Computer-Assisted ; Middle Aged ; Neoplasm Recurrence, Local/*diagnostic imaging ; Octreotide/*analogs & derivatives/chemistry ; Organometallic Compounds/*chemistry ; Positron Emission Tomography Computed Tomography/methods ; Radiopharmaceuticals/chemistry ; Receptors, Somatostatin/*analysis ; Retrospective Studies ; }, abstract = {OBJECTIVE: This study sets out to evaluate patients with increased uptake in breast lesions on [68]Ga-DOTATATE PET/CT (DOTA PET) and determine the clinical significance of somatostatin receptor (SSTR) positive breast lesions.

METHODS: We retrospectively evaluated all patients with increased SSTR uptake in breast lesions on DOTA PET. Patients with physiological (e.g., lactation) or normal variant breast uptake (e.g., mild diffuse glandular uptake) were excluded. The maximum standard uptake value (SUVmax) was calculated using a manually drawn region of interest in the most intense uptake of breast lesions. All lesions were correlated with breast imaging, including mammography and ultrasonography. Histopathological correlation was performed if the lesion was suspicious for malignancy. Lesions were followed up radiologically (1-8 years).

RESULTS: Out of 1573 retrospectively analyzed DOTA PET scans, the incidence of SSTR + breast lesions was measured as 1.1% (n = 18); however, 4 of 18 patients were excluded due to the lack of final diagnosis of lesions. The median age was 35 (range 14-58 years), and all patients were female. The median SUVmax of SSTR + breast lesions was 5.2 (range 1.5-12.6) for a total of 14 patients. Twelve patients had a single SSTR + breast lesion, while 2 patients had multiple SSTR + lesions on bilateral breasts. In 6 patients, single SSTR + lesions were considered as fibroadenoma; in 2 patients, multiple SSTR + lesions were considered as metastases of NET, based on correlative breast imaging. In 6 patients, histopathological confirmation was needed for the final diagnosis. Histopathologic findings confirmed fibroadenoma in 4 patients by biopsy, in 1 patient with surgical removal of the lesion. The last patient who had a history of IDC was diagnosed with a recurrence of IDC with biopsy. The median SUVmax was 5.1 (range 1.5-9.4) for malignant breast lesions and 5.4 (range 2.2-12.6) for benign breast lesions.

CONCLUSION: SSTR + breast lesions on DOTA PET are rarely seen in clinical practice. Uptakes of breast lesions in our cases were variable and not useful for differential diagnosis of lesions. It seems that SSTR + breast lesions should be evaluated with clinical and radiological characteristics, and correlative breast imaging and/or histopathological verification should be performed for suspicious lesions to avoid misdiagnosis.}, } @article {pmid33397202, year = {2021}, author = {Kulwatno, J and Gong, X and DeVaux, R and Herschkowitz, JI and Mills, KL}, title = {An Organotypic Mammary Duct Model Capturing Matrix Mechanics-Dependent Ductal Carcinoma In Situ Progression.}, journal = {Tissue engineering. Part A}, volume = {27}, number = {7-8}, pages = {454-466}, doi = {10.1089/ten.TEA.2020.0239}, pmid = {33397202}, issn = {1937-335X}, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; Cell Line, Tumor ; Female ; Humans ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is a precancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment. In vitro models are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. In this study, we modeled an organotypic mammary duct as a channel molded in a collagen matrix and lined with basement membrane. By adjusting the concentration of collagen (4 and 8 mg/mL), we modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells, including the isogenic MCF10 series that spans the range from healthy to aggressive, behaved within our model. We observed distinct characteristics of breast cancer progression such as hyperplasia and invasion. Normal mammary epithelial cells (MCF10A) formed a single-cell layer on the lumen surface, whereas the most aggressive (MCF10CA1) were several cell layers thick. The model captured collagen concentration-dependent protrusive behaviors by the MCF10A and MCF10CA1 cells, as well as a known invasive cell line (MDA-MB-231). The MCF10A and MCF10CA1 cells extended protrusions into the lower collagen concentration matrix, while the MDA-MB-231 cells fully invaded matrices of either collagen concentration but to a greater distance in the higher collagen concentration matrix. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevant in vitro studies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC. Impact statement The success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development of in vitro models that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. In this study, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.}, } @article {pmid33395878, year = {2020}, author = {Bouri, S and Simon, P and D'Haene, N and Catteau, X and Noël, JC}, title = {Invasive ductal carcinoma arising in borderline phyllode tumor: A potential role of PIK3CA mutation.}, journal = {International journal of surgery case reports}, volume = {77}, number = {}, pages = {701-703}, pmid = {33395878}, issn = {2210-2612}, abstract = {INTRODUCTION: Carcinomatous lesions associated with phyllodes tumors are extremely rare and are found in less than 1% of all cases. To date, the molecular biological mechanisms associated with this carcinomatous transformation remain unknown.

PRESENTATION OF CASE: We present here the case of a 61-year-old patient with invasive ductal of no special type (NST) carcinoma originating in a borderline phyllode tumor with mutation in the PIK3CA gene.

DISCUSSION: To the best of our knowledge, this mutation has never been described in this type of association.

CONCLUSION: Based on these data, we can better understand the ethiopathogenic molecular mechanisms in this type of lesion. Consequently, they could also in the future give rise to new therapeutic alternatives.}, } @article {pmid33393046, year = {2021}, author = {Pardo, JA and Fan, B and Mele, A and Serres, S and Valero, MG and Emhoff, I and Alapati, A and James, TA}, title = {The Role of Oncotype DX[®] Recurrence Score in Predicting Axillary Response After Neoadjuvant Chemotherapy in Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {28}, number = {3}, pages = {1320-1325}, pmid = {33393046}, issn = {1534-4681}, mesh = {*Breast Neoplasms/diagnosis/drug therapy/metabolism ; Chemotherapy, Adjuvant ; Female ; Humans ; Neoadjuvant Therapy ; *Neoplasm Recurrence, Local/diagnosis/drug therapy/metabolism ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {INTRODUCTION: Oncotype DX[®] recurrence score (RS) is well-recognized for guiding decision making in adjuvant chemotherapy; however, the predictive capability of this genomic assay in determining axillary response to neoadjuvant chemotherapy (NCT) has not been established.

METHODS: Using the National Cancer Data Base (NCDB), we identified patients diagnosed with T1-T2, clinically N1/N2, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER +/HER2 -) invasive ductal carcinoma of the breast between 2010 and 2015. Patients with an Oncotype DX[®] RS who received NCT were included. RS was defined as low (< 18), intermediate (18-30), or high (> 30). Unadjusted and adjusted analyses were performed to determine the association between axillary pathologic complete response (pCR) and RS.

RESULTS: This study included a total of 158 women. RS was low in 56 (35.4%) patients, intermediate in 62 (39.2%) patients, and high in 40 (25.3%) patients. The majority of patients presented with clinical N1 disease (89.2%). Axillary pCR was achieved in 23 (14.6%) patients. When stratifying patients with axillary pCR by RS, 11 (47.8%) patients had a high RS, 6 (26.1%) patients had an intermediate RS, and 6 (26.1%) patients had a low RS. Comparing cohorts by RS, 27.5% of patients with high RS tumors had an axillary pCR, compared with only 9.7% in the intermediate RS group, and 10.7% in the low RS group (p = 0.0268).

CONCLUSION: Our findings demonstrate that Oncotype DX[®] RS is an independent predictor of axillary pCR in patients with ER +/HER2 - breast cancers receiving NCT. A greater proportion of patients with a high RS achieved axillary pCR. These results support Oncotype DX[®] as a tool to improve clinical decision making in axillary management.}, } @article {pmid33391657, year = {2020}, author = {De Pauw, V and Navez, J and Holbrechts, S and Lemaitre, J}, title = {Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {12}, pages = {rjaa535}, pmid = {33391657}, issn = {2042-8812}, abstract = {Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.}, } @article {pmid33389809, year = {2021}, author = {Jackson, CR and Felty, CC and Marotti, JD and Rosenkranz, KM and Muller, KE}, title = {Encapsulated papillary carcinoma with and without frank invasion: Comparison of clinicopathologic features and role of axillary staging.}, journal = {The breast journal}, volume = {27}, number = {3}, pages = {209-215}, doi = {10.1111/tbj.14153}, pmid = {33389809}, issn = {1524-4741}, mesh = {Axilla/pathology ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Papillary/pathology ; Female ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; }, abstract = {To investigate clinical and pathologic features of encapsulated papillary carcinomas (EPCs) that may be associated with invasive disease and characterize the axillary staging practices for EPCs at our institution. A pathology database search for cases containing "papillary carcinoma" was performed. Slides were reviewed by two pathologists. Clinicopathological features and axillary staging practices of EPCs with and without invasion were compared. Twenty-five cases of EPCs were identified. Fifteen cases contained a frank invasive tumor (60%), which were all pT1 (0.7 ± 0.56 cm), and the majority were ER-positive, HER2-negative, low-grade IDC-NST. Seventeen patients underwent sentinel lymph node biopsies (SLNB). No nodal metastases were identified. Follow-up was available for 24 patients (mean = 39 ± 29 months); 23 had no NED. Patients that presented with a self-palpated mass (versus screening) were more likely to have an invasive component; however, no pathologic or radiologic features differentiated EPCs with and without frank invasion. Pathologic and radiologic characteristics did not differentiate EPCs with and without frank invasion. EPCs have an excellent prognosis supported by the notable disease-free survival and negative nodal status in our cohort, which supports the notion that patients with EPCs may forgo axillary staging.}, } @article {pmid33389406, year = {2021}, author = {Ha, SM and Chang, JM and Kim, SY and Lee, SH and Kim, ES and Kim, YS and Cho, N and Moon, WK}, title = {Prediction of axillary nodal burden in patients with invasive lobular carcinoma using MRI.}, journal = {Breast cancer research and treatment}, volume = {186}, number = {2}, pages = {463-473}, pmid = {33389406}, issn = {1573-7217}, support = {HI15C1532//Korea Health Industry Development Institute/Republic of Korea ; HA17C0056//Ministry of Health and Welfare/ ; }, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate clinical and imaging features associated with a high nodal burden (≥ 3 metastatic lymph nodes [LNs]) and compare diagnostic performance of US and MRI in patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).

METHODS: Retrospective search revealed 239 patients with ILC and 999 with IDC who underwent preoperative US and MRI between January 2016 and June 2019. Patients with ILC were propensity-score-matched with patients with IDC. Univariate and multivariate logistic regression analyses were performed to determine factors associated with ≥ 3 metastatic LNs.

RESULTS: 412 patients (206 ILC and 206 IDC) were evaluated. Of all patients with ILC, 27.2% (56/206) were node-positive and 7.8% (16/206) showed a high nodal burden. In multivariate analysis, the clinical N stage was the only independent factor associated with a high nodal burden in patients with IDC (odds ratio [OR] 6.24; 95% confidence interval [CI] 1.57-24.73; P = 0.009), but not in patients with ILC. Increased cortical thickness with loss of fatty hilum on US was associated with a high nodal burden in patients with ILC (OR 58.40; 95% CI 5.09-669.71; P = 0.001) and IDC (OR 24.14; 95% CI 3.52-165.37; P = 0.001), while suspicious LN findings at MRI were independently associated with a high nodal burden in ILC only (OR 13.94; 95% CI 2.61-74.39; P = 0.002).

CONCLUSION: In patients with ILC, MRI findings of suspicious LNs were helpful to predict a high nodal disease burden.}, } @article {pmid33389280, year = {2021}, author = {Rosenberg, A and Hamiel, D}, title = {Reducing Test Anxiety and Related Symptoms Using a Biofeedback Respiratory Practice Device: A Randomized Control Trial.}, journal = {Applied psychophysiology and biofeedback}, volume = {46}, number = {1}, pages = {69-82}, pmid = {33389280}, issn = {1573-3270}, mesh = {Adult ; *Biofeedback, Psychology ; *Breathing Exercises ; Depression/psychology ; Female ; Health Education ; Humans ; Male ; Quality of Life/psychology ; Students ; Surveys and Questionnaires ; *Test Anxiety/psychology/therapy ; Young Adult ; }, abstract = {Test Anxiety is a widespread psychological phenomenon. With prevalence rates of 20-40 percent of university students, it impedes adaptive functioning and life quality. Many available treatments for Test Anxiety involve the intervention of clinicians and usually a few months are required before symptom reduction is reported. The present randomized controlled trial examined a simple behavioral intervention-the use of breathing tools-as an exclusive therapy for Test Anxiety. Specifically, the efficacy of a biofeedback respiratory practice device was examined. 34 students were assigned to 3 treatment groups during their exam period: Biofeedback device group, self-directed breathing exercise group, and psychoeducation group. Self-report measures of Test Anxiety were collected pre- and post-intervention. Participants also reported additional exploratory measures such as depression and anxiety, quality of life, and their perceived adaptive functioning post-intervention. The results reveal that only participants from the biofeedback device group reported a significant reduction in Test Anxiety symptoms (p's < 0.05). Participants from the biofeedback device group also reported a decrease in depression and anxiety symptoms and an increase in psychological wellbeing (p's < 0.05), a subscale of the quality of life questionnaire. Findings support the notion that using biofeedback respiratory devices may reduce students' Test Anxiety symptoms. Indications for further research are discussed.}, } @article {pmid33385274, year = {2021}, author = {Kato, M and Hirakawa, A and Sato, H and Hanazawa, R and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T}, title = {Grade group 2 (10% ≥ GP4) patients have very similar malignant potential with grade group 1 patients, given the risk of intraductal carcinoma of the prostate.}, journal = {International journal of clinical oncology}, volume = {26}, number = {4}, pages = {764-769}, pmid = {33385274}, issn = {1437-7772}, mesh = {*Carcinoma, Intraductal, Noninfiltrating ; Humans ; Male ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Prostate/surgery ; Prostatectomy ; *Prostatic Neoplasms/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: It has been argued that grade group 2 (GG2) with a low Gleason pattern 4 (GP4) proportion should be an indication for active surveillance (AS) of prostate cancer (PCa). However, the cut-off GP4 proportion for AS remains unclear. Here, we evaluated the effect of GP4 proportion and IDC-P on cancer recurrence following radical prostatectomy (RP) in GG1 and GG2 patients, and identified candidates for AS.

METHODS: We retrospectively evaluated 646 patients with PCa who underwent RP between 2005 and 2014, and whose specimens were of GG1 or GG2 status.

RESULTS: The GGs were as follows: GG1, 25.2% (n = 163); GG2 (5% ≥ GP4), 11.4% (n = 74); GG2 (5% < GP4 ≤ 10%), 25.9% (n = 167); and GG2 (20% ≤ GP4), 37.5% (n = 242). IDC-P was detected in 26 patients (4%), i.e., in 2/167 GG2 (5% < GP4 ≤ 10%; 1%) cases and 24/242 GG2 (20% ≤ GP4; 10%) cases. GG2 patients with IDC-P exhibited a significantly poorer prognosis than did those without IDC-P (P < 0.0001), as did GG2 (20% ≤ GP4) patients without IDC-P (P < 0.05). The GG2 (5% ≥ GP4) and (5% < GP4 ≤ 10%) groups exhibited prognoses similar to those of the GG1 patients. In multivariate analysis, GG2 (20% ≤ GP4) without IDC-P, the presence of IDC-P, and the prostate-specific antigen level at diagnosis significantly predicted prognosis (P < 0.05, < 0.0001, and < 0.0001, respectively).

CONCLUSION: Our findings suggest that GG2 (GP4 ≤ 10%) patients could be indicated for AS, similar to GG1 patients, given the risk of IDC-P tumors.}, } @article {pmid33380828, year = {2020}, author = {Zhu, X and Xu, M and Zhao, X and Shen, F and Ruan, C and Zhao, Y}, title = {The Detection of Plasma Soluble Podoplanin of Patients with Breast Cancer and Its Clinical Signification.}, journal = {Cancer management and research}, volume = {12}, number = {}, pages = {13207-13214}, pmid = {33380828}, issn = {1179-1322}, abstract = {BACKGROUND: Podoplanin (PDPN) is a type-1 membrane sialoglycoprotein that is expressed in many cancer tumors including breast cancer; nonetheless, its roles in tumor occurrence, development, and metastasis are unclear. In this study, we aimed to investigate the clinical significance of plasma soluble PDPN (sPDPN) levels in patients with breast cancer and its significance in the diagnosis and metastasis.

MATERIALS AND METHODS: Blood samples from healthy controls (CTL), patients with fibroadenomas of breast (FOB), and breast cancer (pathological type: invasive ductal carcinoma, IDC) were collected. sPDPN levels in the plasma of CTL and patients with FOB and IDC were measured by the ELISA.

RESULTS: The plasma sPDPN levels in IDC patients (159 cases, 22.59±3.70 ng/mL) were higher than those in FOB patients (50 cases, 8.29±1.09 ng/mL; P<0.05) and CTL (100 cases, 1.21±0.12 ng/mL; P<0.0001). The sPDPN levels in patients at stage III and stage IV (30.08±4.66 ng/mL) were higher than in patients at stage I and stage II (11.84±1.12 ng/mL; P=0.005). The sPDPN levels in patients with high-moderate and moderate differentiation (17.50±3.02 ng/mL) were lower than those in patients with moderately low and low differentiation (35.73±4.26 ng/mL; P=0.026). The sPDPN levels in patients with metastasis (30.60±4.27 ng/mL) were much higher than those in patients without metastasis (13.02±1.30 ng/mL; P=0.017).

CONCLUSION: Plasma sPDPN may be used as a new marker for the determination of the clinical stage, differentiation degree, and metastasis status of breast cancer.}, } @article {pmid33377394, year = {2022}, author = {Toprak, N and Toktas, O and Ince, S and Gunduz, AM and Yokus, A and Akdeniz, H and Ozkacmaz, S}, title = {Does ARFI elastography complement B-mode ultrasonography in the radiological diagnosis of idiopathic granulomatous mastitis and invasive ductal carcinoma?.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {63}, number = {1}, pages = {28-34}, doi = {10.1177/0284185120983568}, pmid = {33377394}, issn = {1600-0455}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diagnosis, Differential ; *Elasticity Imaging Techniques ; Female ; Granulomatous Mastitis/*diagnostic imaging ; Humans ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging ; Prospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a chronic, unpleasant autoimmune inflammatory condition and is clinically and radiologically often confused with breast malignancy.

PURPOSE: To investigate the contributions of qualitative and quantitative aspects of acoustic radiation force impulse (ARFI) elastography to the differential diagnosis between IGM and invasive ductal carcinoma (IDC) in the breast.

MATERIAL AND METHODS: Ninety-four women with IDC and 39 with IGM were included in the study. Shear wave velocity (SWV) was calculated for all lesions using quantitative elastography. Next, each lesion's correspondence on qualitative elastographic images to those on the B-mode images was evaluated: pattern 1, no findings on elastography images; pattern 2, lesions that were bright inside; pattern 3, lesions that contained both bright and dark areas; and pattern 4, lesions that were dark inside. Pattern 4 was subdivided into 4a (dark area same size as lesion) and 4b (dark area larger than lesion size). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated.

RESULTS: The mean SWV based on ARFI elastography was 3.78 ± 1.26 m/s for IGM and 5.34 ± 1.43 m/s for IDC lesions (P < 0.05). Based on qualitative ARFI elastography, IDC lesions were mostly classified as pattern 4b, while IGM lesions were mostly classified as pattern 1 or 2 (P = 0.01). Evaluation of both the qualitative and quantitative aspects of ARFI elastography yielded a sensitivity of 89% and specificity of 84%.

CONCLUSION: ARFI elastography may facilitate the differential diagnosis between IGM and IDC.}, } @article {pmid33371804, year = {2021}, author = {Ben-Gal Dahan, A and Mikulincer, M}, title = {Attachment and task persistence: attachment orientations, perception of teacher's responsiveness, and adolescents' persistence in academic tasks.}, journal = {Attachment & human development}, volume = {23}, number = {5}, pages = {665-686}, doi = {10.1080/14616734.2020.1865425}, pmid = {33371804}, issn = {1469-2988}, mesh = {Adolescent ; Anxiety ; Anxiety Disorders ; Humans ; *Motivation ; *Object Attachment ; Perception ; }, abstract = {The goal of the two studies reported here was to examine the contribution of adolescents' attachment orientations (anxiety, avoidance) and their perception of teacher's responsiveness to persistence in academic tasks. In Study 1 (N = 160), we assessed self-reports of persistence in schoolwork. In Study 2 (N = 240), we manipulated the symbolic presence of participants' teacher (teacher priming) and assessed their actual persistence in a cognitive task. Across the two studies, attachment anxiety was associated with decreased persistence, and the perception of teacher as a responsive figure contributed to heightened persistence and buffered the detrimental effects of attachment anxiety. Study 2's findings also showed that the beneficial effects of perceived teacher's responsiveness on actual task persistence were found only when the teacher was made contextually salient but not when the teacher was not salient. We discussed the dispositional and contextual sources of attachment security that contribute to task persistence.}, } @article {pmid33371069, year = {2020}, author = {Yue, L and Wentao, L and Xin, Z and Jingjing, H and Xiaoyan, Z and Na, F and Tonghui, M and Dalin, L}, title = {Human epidermal growth factor receptor 2-positive metastatic breast cancer with novel epidermal growth factor receptor -ZNF880 fusion and epidermal growth factor receptor E114K mutations effectively treated with pyrotinib: A case report.}, journal = {Medicine}, volume = {99}, number = {51}, pages = {e23406}, pmid = {33371069}, issn = {1536-5964}, mesh = {Acrylamides/administration & dosage/*therapeutic use ; Adult ; Aminoquinolines/administration & dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; ErbB Receptors/*genetics/*metabolism ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, ErbB-2/antagonists & inhibitors/metabolism ; }, abstract = {INTRODUCTION: In about 15% to 20% of breast cancer cases, human epidermal growth factor receptor 2 (HER2) over-expression or gene-amplification is associated with poor prognosis. Thanks to the development of target therapies, HER2 positive patients can be managed using HER2-targeting drugs. There are several kinds ofHER2 inhibitors, such as trastuzumab, lapatinib, and pyrotinib. Pyrotinib which exert different functions, of note, the latest generation of the drug, is an irreversible small-molecule tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) (HER1) and/or HER2 and/or HER4. Both lapatinib and pyrotinib potentially target EGFR and/or HER2, but in some instances, induces different responses of patients with EGFR and/or HER2 mutations. This is attributed to the different mutations in EGFR and HER2 genes, which may form distinct types of HER2 dimers, with different binding capacities to drugs.

PATIENT CONCERNS: Five years ago, a patient underwent a radical mastectomy in an external hospital. Results of the resection histopathology revealed an invasive ductal carcinoma, pT3N0M0, stage IIB, HER2 positive. The lady patient received 6 cycles of adjuvant chemotherapy and was subjected to adjuvant trastuzumab therapy for 1 year. After a regular 1-year follow-up and in March 2018, she complained of chest pain and visited our hospital. We diagnosed her with metastatic breast cancer, positive for HER2.

DIAGNOSIS: positron emission tomography/computed tomography showed multiple metastases in the lung and sternum, while the breast lesions did not progress, the curative effect of which we evaluated as a progressive disease. Then, lapatinib integrated with chemotherapy was administered to the patient. After 5 cycles of the treatment, the patient experienced lower back pain. Through CT examination, it was revealed that she had multiple metastases in the lung and sternum, in addition to new metastases in the lumbar spine and right lobe of the liver. Moreover, magnetic resonance imaging revealed multiple metastases in the brain, and the disease further progressed. The results of circulating tumor DNA assays showed that other than HER2 amplification, novel EGFR-ZNF880 fusion and EGFR E114K mutations developed.

INTERVENTIONS: The patient was administered with a combination of pyrotinib with chemotherapy.

OUTCOMES: After 2 months of pyrotinib treatment, the metastases of the lung, sternum, lumbar spine, and right lobe of the liver disappeared. Also, the size of the brain metastases reduced while bone metastases were relieved. The curative effect was evaluated as a partial response. Following the results of circulating tumor DNA assays, HER2 amplification, EGFR-ZNF880 fusion, and EGFR E114K mutations disappeared. However, since a small lesion was present in the brain, the patient was subjected to radiotherapy in the head. Notably, after 9 months treatment with pyrotinib, enhanced CT indicated that tumors in the breast, liver, both lungs, brain, and bone were under control. The patient continually received oral pyrotinib, however, a new brain lesion appeared 6 months later. Overall, we managed to regulate the efficacy of pyrotinib for up to 15 months.

CONCLUSION: This case report demonstrates that EGFR-ZNF880 fusion and EGFR E114K mutations may contribute or lead to the formation of a special HER2 dimer, which is rapidly resistant to lapatinib but sensitive to pyrotinib. Of note, this is the first report that such a new fusion has been found.}, } @article {pmid33370550, year = {2021}, author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q}, title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.}, journal = {Viral immunology}, volume = {34}, number = {2}, pages = {96-111}, doi = {10.1089/vim.2020.0052}, pmid = {33370550}, issn = {1557-8976}, mesh = {Animals ; *Hepatitis B/prevention & control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunity ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology/therapeutic use ; *beta-Defensins/immunology/therapeutic use ; }, abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3[+]/CD4[+] T cells and CD3[+]/CD8[+] T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.}, } @article {pmid33362595, year = {2020}, author = {Haruvi Catalan, L and Levis Frenk, M and Adini Spigelman, E and Engelberg, Y and Barzilay, S and Mufson, L and Apter, A and Benaroya Milshtein, N and Fennig, S and Klomek, AB}, title = {Ultra-Brief Crisis IPT-A Based Intervention for Suicidal Children and Adolescents (IPT-A-SCI) Pilot Study Results.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {553422}, pmid = {33362595}, issn = {1664-0640}, abstract = {In recent years, suicidal behaviors have shown substantial increase worldwide. This trend is also prominent in Israel and has led to a dramatic increase in mental health treatment demand resulting in long wait times and low treatment acceptance rate. To address the critical need in crisis intervention for children and adolescents at suicidal risk we developed an ultra-brief acute crisis intervention, based on Interpersonal Psychotherapy (IPT). IPT is an evidence-based intervention for various psychopathologies among different age groups. The current adaptation of IPT-A is comprised of five weekly sessions, followed by monthly follow-up caring email contacts to the patients and their parents, over a period of 3 months. This paper aims to review the theoretical foundation of this intervention, describe the research design, and present preliminary results of a pilot study. Preliminary Results from our samples of 26 adolescents indicate meaningful trends for both the suicidal ideation (SIQ) and depression (MFQ) outcome measures. Significant interaction was found concerning suicidal ideation but not for depression. Main limitations include small sample size and stratified controls. The treatment appears to be safe, feasible and acceptable and initial results show promising trends to support further study of the approach.}, } @article {pmid33362306, year = {2020}, author = {Hasan-Aslih, S and Shuman, E and Pliskin, R and van Zomeren, M and Saguy, T and Halperin, E}, title = {With or without you: The paradoxical role of identification in predicting joint and ingroup collective action in intergroup conflict.}, journal = {European journal of social psychology}, volume = {50}, number = {6}, pages = {1334-1343}, pmid = {33362306}, issn = {0046-2772}, abstract = {While we have a rich understanding of the motivations of disadvantaged group members to act collectively with their group, especially the important role played by identification, we know less about the disadvantaged's motivations to engage in joint action with the advantaged. This research examines the role of identification in predicting joint and ingroup collective action in intergroup conflicts. Since joint action inherently diffuses the perception of "us versus them", we propose that identification predicts ingroup action, but not joint action. We also examine conflict intensity as a moderator, and examine how changing identification is linked to change in support for joint action. We test these hypotheses in a three-wave longitudinal study in the Palestinian-Israeli conflict. Results support our hypotheses, demonstrating that identification positively predicts ingroup action but not necessarily joint action, and that when conflict intensifies, changes in identification are negatively related to joint action with outgroup members.}, } @article {pmid33360037, year = {2021}, author = {Alawami, HA and Al-Faraj, ZH and Al Duhileb, MA and AlOmran, HA and El Sayed, AA}, title = {Unusual collision tumor with infiltrating ductal carcinoma and breast skin squamous cell carcinoma: A case report and literature review.}, journal = {International journal of surgery case reports}, volume = {78}, number = {}, pages = {167-171}, pmid = {33360037}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast cancer is the most common diagnosed cancer among women worldwide. Invasive ductal carcinoma (IDC) is the most common type, on the other hand, squamous cell carcinoma of the skin (SCC) overlying the breast is a rare tumor. The co-presence of two tumor types in one organ is even a rarer entity, termed as collision tumor. Only 3 known cases of collision tumor with breast invasive ductal and skin squamous carcinoma were reported in the literature.

CASE PRESENTATION: An otherwise medically free 91-year-old, postmenopausal, female presented with left breast fungating mass for four months. Pre-operative core tissue biopsy and incisional skin biopsy revealed two distinct tumor subtypes of invasive ductal carcinoma, positive for progesterone, estrogen receptors and negative for human epidermal growth factor receptor 2, as well as skin squamous cell carcinoma, and axillary lymph node metastasis. Patient underwent left breast modified radical mastectomy and split skin grafting for wound closure. The final histopathology was consistent with grade 2 IDC. The nipple and areola complex were involved by moderately differentiated squamous cell carcinoma. Currently patient on adjuvant hormonal treatment. Follow up showed no local recurrence or distal metastasis.

CONCLUSION: Collision tumors of the breast with IDC and SCC of the overlying skin is very rare. The surgeon has to be aware of of such entity as the proper peri-operative management should be tailored to target the most aggressive histologic subtype.}, } @article {pmid33360004, year = {2021}, author = {Venkatesh, SL and Oseni, TO and Bahl, M}, title = {Symptomatic ductal carcinoma in situ (DCIS): Upstaging risk and predictors.}, journal = {Clinical imaging}, volume = {73}, number = {}, pages = {101-107}, doi = {10.1016/j.clinimag.2020.11.050}, pmid = {33360004}, issn = {1873-4499}, mesh = {Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; }, abstract = {PURPOSE: To estimate the upstaging risk of symptomatic ductal carcinoma in situ (DCIS) to invasive disease and to identify features related to upstaging risk.

MATERIALS AND METHODS: This retrospective investigation includes symptomatic women with DCIS at core needle biopsy from January 2007 to December 2016 at a large academic institution. Patient characteristics, findings at imaging, core needle biopsy histopathology results, and final surgical histopathology results were retrieved from the medical records. Using standard statistical tests, patient, imaging, and pathology features were compared between DCIS cases that were upstaged to invasive disease at surgery versus cases that were not upstaged.

RESULTS: From 2007 to 2016, fewer than 5% (63/1399) of women diagnosed with DCIS presented with symptoms. Therefore, 63 women (mean age, 51; range, 27-88 years) comprised the study cohort. 84.1% (n = 53) presented with an area of clinical concern, and 15.9% (n = 10) presented with pathologic nipple discharge. The most common finding at mammography was calcifications with or without an associated asymmetry or mass (74.1%, 40/54). The upstaging rate of symptomatic DCIS to invasive disease was 34.9% (22/63). Imaging modality used for biopsy was associated with higher upstaging risk, with cases that were biopsied under MRI guidance accounting for 22.7% of upstaged cases versus 4.9% of non-upstaged cases (p = 0.03).

CONCLUSIONS: Women with DCIS uncommonly present with symptoms, and the upstaging rate of symptomatic DCIS is high at nearly 35%. Biopsy modality type of MRI is associated with higher upstaging risk.}, } @article {pmid33356097, year = {2021}, author = {Zhong, S and Wong, HC and Low, HY and Zhao, R}, title = {Phototriggerable Transient Electronics via Fullerene-Mediated Degradation of Polymer:Fullerene Encapsulation Layer.}, journal = {ACS applied materials & interfaces}, volume = {13}, number = {1}, pages = {904-911}, doi = {10.1021/acsami.0c18795}, pmid = {33356097}, issn = {1944-8252}, abstract = {Transient electronics is an emerging class of electronics that has attracted a lot of attention because of its potential as an environmental-friendly alternative to the existing end-of-life product disposal or treatments. However, the controlled degradation of transient electronics under environmentally benign conditions remains a challenge. In this work, the tunable degradation of transient electronics including passive resistor devices and active memory devices was realized by photodegradable thin polymer films comprising fullerene derivatives, [6,6]-phenyl-C61-butyric acid methyl esters (PCBM). The photodegradation of polymer:PCBM under an aqueous environment is triggered by ultraviolet (UV) light. Experimental results demonstrate that the addition of PCBM in commodity polymers, including but not limited to polystyrene, results in a catalytic effect on polymer photodegradation when triggered by UV light. The degradation mechanism of transient electronics is ascribed to the photodegradation of polymer:PCBM encapsulation layers caused by the synergistic effect between UV and water exposure. The polymer:PCBM encapsulation system presented herein offers a simple way to achieve the realization of light-triggered device degradation for bioapplication and expands the material options for tailorable degradation of transient electronics.}, } @article {pmid33355663, year = {2021}, author = {Duguid, RC and Al Reesi, M and Bartlett, AW and Palasanthiran, P and McMullan, BJ}, title = {Impact of Infectious Diseases Consultation on Management and Outcome of Staphylococcus aureus Bacteremia in Children.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {10}, number = {5}, pages = {569-575}, doi = {10.1093/jpids/piaa155}, pmid = {33355663}, issn = {2048-7207}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Bacteremia/drug therapy ; Child ; *Communicable Diseases/drug therapy ; Humans ; Referral and Consultation ; Retrospective Studies ; *Staphylococcal Infections/drug therapy ; Staphylococcus aureus ; Treatment Outcome ; }, abstract = {BACKGROUND: To examine the impact of infectious diseases consultation (IDC) on the management and outcome of Staphylococcus aureus bacteremia (SAB) in children.

METHODS: A retrospective cohort study of children with SAB at a teritary pediatric hospital (January 2009-June 2015) identified by medical record review as to whether they received an IDC for SAB at the discretion of the admitting physician or surgeon was conducted. Differences in management and outcomes for those with and without IDC were evaluated, and multivariate regression analysis was used to determine factors associated with cure.

RESULTS: There were 100 patients included in the analysis. Fifty-five patients received IDC and 45 had no IDC (NIDC). Appropriate directed therapy within 24 hours (54/55 = 98.2% vs 34/45 = 75.6%, P < .01), choice (54/55 = 98.2% vs 37/45 = 82.2%, P < .01), dose (54/55 = 98.2% vs 36/45 = 80%, P < .01), and duration (52/55 = 94.5% vs 24/45 = 53.3%, P < .01) of directed antibiotic therapy were appropriate in more IDC group patients. Achievement of source control in indicated cases was also more common in the IDC group (28/32 = 87.5% vs 5/26 = 19.1%, P < .01). Appropriate investigation with repeat blood cultures and echocardiograms was not significantly different. All 55 patients in the IDC group had a complete response (cure) compared with 40 of the 45 (88.9%) patients in the NIDC group: 2 patients died and 3 patients had a relapse of infection with subsequent cure. In multivariate regression analysis, methicillin-susceptible SAB and IDC were factors independently associated with cure.

CONCLUSIONS: Children who received IDC for SAB in a tertiary pediatric setting were more likely to have appropriate investigations and management and had improved outcomes.}, } @article {pmid33348399, year = {2020}, author = {Reis, APAM and Teixeira, CMS and Medeiros, ARL and Chaves, KZC and Albuquerque, CR and Melo, MR}, title = {Sociodemographic and Clinical-pathological Study of Molecular Subtitles of Breast Carcinoma in a Reference Unit of Maranhão.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {42}, number = {12}, pages = {820-828}, pmid = {33348399}, issn = {1806-9339}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*epidemiology/etiology/pathology ; Cross-Sectional Studies ; Demography ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Medical Records ; Middle Aged ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Social Class ; }, abstract = {OBJECTIVE: To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry.

METHODS:  A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive.

RESULTS:  A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others.

CONCLUSION:  It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.}, } @article {pmid33344602, year = {2020}, author = {Yang, P and Peng, SJ and Dong, YM and Yang, L and Yang, ZY and Hu, XE and Bao, GQ}, title = {Neoadjuvant targeted therapy for apocrine carcinoma of the breast: A case report.}, journal = {World journal of clinical cases}, volume = {8}, number = {23}, pages = {6036-6042}, pmid = {33344602}, issn = {2307-8960}, abstract = {BACKGROUND: Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice. Neoadjuvant therapy, especially neoadjuvant targeted therapy, has rarely been reported for apocrine carcinoma of the breast.

CASE SUMMARY: A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy. The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status (estrogen receptor and progesterone receptor) but showed overexpression of human epidermal factor receptor 2 (HER-2). Moreover, positive expression of androgen receptor (approximately 60%) and gross cystic disease fluid protein 15 was observed. The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen (docetaxel, carboplatin area under curve 6 and trastuzumab) every 21 d. The mass in the left breast was significantly reduced, and pain in the breast and left upper arm also improved.

CONCLUSION: HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.}, } @article {pmid33342987, year = {2020}, author = {Shinseki, K and Takahashi, M and Kushima, A and Nakamoto, T and Wakata, M and Nakajima, T and Toda, T and Ito, K and Fujibayashi, M}, title = {[One Case of Accessory Breast Cancer Complicated by Contralateral Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {12}, pages = {1703-1705}, pmid = {33342987}, issn = {0385-0684}, mesh = {Axilla ; *Breast Diseases ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/complications/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.}, } @article {pmid33342807, year = {2020}, author = {Mohapatra, M and Sarma, YS}, title = {A study on clinico-pathological assessment of response to neoadjuvant chemotherapy in breast carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {6}, pages = {1419-1425}, doi = {10.4103/jcrt.JCRT_295_19}, pmid = {33342807}, issn = {1998-4138}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/metabolism ; Biopsy, Large-Core Needle/statistics & numerical data ; Breast/drug effects/pathology/surgery ; Breast Neoplasms/diagnosis/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/*therapy ; Chemotherapy, Adjuvant/methods/statistics & numerical data ; Clinical Decision-Making/methods ; Female ; Humans ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis/diagnosis/pathology/*therapy ; Mastectomy, Segmental/statistics & numerical data ; Middle Aged ; Neoadjuvant Therapy/*methods/statistics & numerical data ; Neoplasm Grading ; Neoplasm Staging ; Neoplasm, Residual ; Patient Selection ; Prognosis ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {CONTEXT: Neoadjuvant chemotherapy (NACT) has become a strategy in the multidisciplinary treatment approach to breast cancer. Since clinical and radiological responses do not correlate well with residual tumor after treatment, pathological evaluation of tumor response to chemotherapy is essential for accurate assessment.

AIMS: The aim of this study is to assess clinicopathological response to NACT in patients with invasive breast carcinoma.

SETTINGS AND DESIGN: Single institution, retrospective study was conducted for 4 years.

SUBJECTS AND METHODS: The study included 95 cases with the clinical diagnosis of locally advanced breast cancer and invasive breast carcinoma on histopathological examination of core needle biopsy/lumpectomy specimen. These cases were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors and treated with four cycles of NACT (adriamycin-cyclophosphamide) therapy. Histopathological examination of postchemo modified radical mastectomy specimens was performed following standard protocol. The pathological response of tumor to chemotherapy was assessed on Miller-Payne grading (MPG) and residual disease in breast and lymph node (RDBN) level.

STATISTICAL ANALYSIS USED: Data were analyzed in percentages and presented in charts and tables.

RESULTS: Histopathological examination of pre-chemo biopsy specimens revealed invasive ductal carcinoma No special type (NST) in maximum, 89 (93.7%) cases. Majority 43 (45.3%) cases were HER2-positive followed by estrogen receptor-positive and/or progesterone receptor positive and HER2-positive type seen in 23 (24.2%) cases and 22 (23.1%) cases were triple negative. Sixteen (16.8%) and 76 (80%) cases showed pathological complete response (pCR) and partial pathological response, respectively, to NACT on MPG; 12 (12.6%) and 83 (87.4%) cases showed pCR and residual disease, respectively, on RDBN level. Majority 37.5% and 50% of cases showing pCR on MPG and RDBN level, respectively, were triple negative.

CONCLUSIONS: This study highlights the clinicopathological response to NACT in carcinoma breast patients and identifies the molecular subtypes of these patients likely to respond to NACT.}, } @article {pmid33342786, year = {2020}, author = {Yadav, BS and Sharma, SC and Singh, R and Dahiya, D and Ghoshal, S}, title = {Male breast cancer: Outcome with adjuvant treatment.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {6}, pages = {1287-1293}, doi = {10.4103/jcrt.JCRT_1305_16}, pmid = {33342786}, issn = {1998-4138}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms, Male/*mortality/pathology/*therapy ; Chemotherapy, Adjuvant ; Humans ; Male ; Mastectomy ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/*mortality/pathology/therapy ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Male breast cancer (MBC) incidence is <1%, but it is increasing. MBC incidence increases with age. There are no randomized trials on MBC because of low number of patients seen in any institution and hence its management is derived from breast cancer (BC) in women. In this study, we analyzed outcome in MBC patients with adjuvant treatment.

MATERIALS AND METHODS: From 1991 to 2014, 81 men with BC were retrospectively analyzed for demographic, clinicopathological, and treatment outcomes. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. DFS and OS were estimated using Kaplan-Meier method and compared between patients receiving and not receiving adjuvant treatment using log-rank test.

RESULTS: The median age was 57 years (range 30-86 years). Right, left, and bilateral BCs were seen in 41 (51%), 38 (47%), and 2 (2%) men, respectively. The mean duration of symptoms was 25 months (range 1-240 months). Comorbidity and family history was present in 31 (38%) and 3 (4%) men, respectively. The mean tumor size was 5 cm × 5 cm (range, 1 cm × 1 cm to 10 cm × 10 cm). Nipple was involved in 46 (57%) men. Early, locally advanced, and metastatic disease were seen in ??30 (37%), 34 (42%), and 17 (21%) men, respectively. Majority (71, 88%) of men had invasive ductal carcinoma histology. In radically treated 64 men, neoadjuvant chemotherapy was given to 12 (19%) patients (fluorouracil, adriamycin, and cyclophosphamide [FAC] to 9 and FAC + taxanes to 3), with CR in 4 (33.3%) and partial response (PR) in 8 (66.7%) patients. Mastectomy was done in 55 (86%) and wide local excision in 9 (14%) men. Margins and nodes were positive in 17 (27%) and 38 (59%) men, respectively. Estrogen receptor, PR, and human epidermal growth factor receptor 2/neu positive were seen in 27 (42%), 17 (26.5%), and 2 (3%) patients, respectively. Adjuvant hypofractionated radiotherapy, chemotherapy, and tamoxifen were received by 51 (80%), 35 (55%), and 45 (70%) men, respectively. Median follow-up was 60 months (range 4-278 months). Locoregional recurrence occurred in 8 (12.5%) and distant metastasis in 22 (34%) men, respectively. DFS and OS at 10 years were 42% and 53%, respectively. DFS and OS were significantly better in men with adjuvant radiation (54% vs. 24%, P = 0.007 and 57% vs. 35%, P = 0.022, respectively) and hormonal therapy (57% vs. 14.5%, P = 0.004 and 62% vs. 39%, P = 0.045, respectively). Chemotherapy had no impact on DFS and OS.

CONCLUSION: Adjuvant hypofractionated radiotherapy and hormonal therapy significantly improved DFS and OS in MBC patients. Chemotherapy had no impact on DFS and OS.}, } @article {pmid33336932, year = {2021}, author = {Liang, RB and Yu, K and Wu, JL and Liu, JX and Lin, Q and Li, B and Zhang, YQ and Ge, QM and Li, QY and Shu, HY and Shao, Y}, title = {Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma.}, journal = {Cancer medicine}, volume = {10}, number = {3}, pages = {824-832}, pmid = {33336932}, issn = {2045-7634}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/metabolism/*pathology/surgery ; Case-Control Studies ; Eye Neoplasms/epidemiology/metabolism/*secondary/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) is a major type of breast cancer. Ocular metastasis (OM) in IDC is rarely seen, but patients with OM often have a poor prognosis. Furthermore, OM is difficult to detect in the early stages by common imaging examinations. In the present study, we tried to figure out the risk factors of OM in IDC and evaluate their diagnostic values for early detection. There were 1192 IDC patients who were divided into two groups according to ocular metastasis involved in this study. Clinical parameters of those patients were used to detect differences. The binary logistic regression test was then used to determine the risk factors of OM in IDC. Furthermore, ROC curves of both single and combined risk factors were established to examine their diagnostic values. The incidence of axillary lymph node metastases was significantly higher in the OM group (p = 0.002). Higher carbohydrate antigen 153 (CA153), lower apolipoprotein A1 (ApoA1), and hemoglobin (Hb) were risk factors for OM in IDC (p < 0.001, p < 0.001, p = 0.038, respectively). In the single risk factor ROC analysis, cutoff values of CA153, ApoA1, and Hb were 43.3 u/mL (CI: 0.966-0.984, p < 0.001), 1.11 g/L (CI: 0.923-0.951, p < 0.001), and 112 g/L (CI: 0.815-0.857, p < 0.001), respectively. Among the ROC curves of combined risk factors, CA153+ApoA1+Hb had the best accuracy, with the sensitivity and specificity of 89.47% and 99.32%, respectively (CI: 0.964-0.983, p < 0.001). CA153, ApoA1, and Hb are risk factors for OM in IDC. In clinical practice, the three parameters could be used as predictive factors for the early detection of OM.}, } @article {pmid33335279, year = {2021}, author = {Zeng, Y and Gao, W and Chen, X and Shen, K}, title = {Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component.}, journal = {British journal of cancer}, volume = {124}, number = {5}, pages = {975-981}, pmid = {33335279}, issn = {1532-1827}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.

METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.

RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.

CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.}, } @article {pmid33331427, year = {2020}, author = {Bertoldi, AS and Guetter, CR and Coltro, GA and Vosgerau, LM and Brighenti, LMV and Fauat, NI and Kubrusly, FB and Marques, CAM and Kubrusly, LF}, title = {CARVEDILOL AS PRIMARY PROPHYLAXIS FOR GASTRIC VARICEAL BLEEDING IN PORTAL HYPERTENSION MODEL IN RATS.}, journal = {Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery}, volume = {33}, number = {3}, pages = {e1525}, pmid = {33331427}, issn = {2317-6326}, mesh = {Adrenergic beta-Antagonists/*administration & dosage ; Animals ; Antihypertensive Agents/*administration & dosage ; Carvedilol/*administration & dosage ; Esophageal and Gastric Varices/complications/prevention & control ; Gastrointestinal Hemorrhage/etiology/*prevention & control ; Hypertension, Portal/*complications ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: Portal hypertension (PH) can be measured indirectly through a hepatic vein pressure gradient greater than 5 mmHg. Cirrhosis is the leading cause for PH and can present as complications ascites, hepatic dysfunction, renal dysfunction, and esophagogastric varices, characterizing gastropathy.

AIM: To evaluate the use of carvedilol as primary prophylaxis in the development of collateral circulation in rats submitted to the partial portal vein ligament (PPVL) model.

METHOD: This is a combined qualitative and quantitative experimental study in which 32 Wistar rats were divided into four groups (8 animals in each): group I - cirrhosis + carvedilol (PPVL + C); group II - cirrhosis + vehicle (PPVL); group III - control + carvedilol (SO-sham-operated + C); group IV - control + vehicle (SO-sham-operated). After seven days of the surgical procedure (PPVL or sham), carvedilol (10 mg/kg) or vehicle (1 mL normal saline) were administered to the respective groups daily for seven days.

RESULTS: The histological analysis showed no hepatic alteration in any group and a decrease in edema and vasodilatation in the PPVL + C group. The laboratory evaluation of liver function did not show a statistically significant change between the groups.

CONCLUSION: Carvedilol was shown to have a positive effect on gastric varices without significant adverse effects.}, } @article {pmid33329930, year = {2020}, author = {Gelezhe, PB and Blokhin, IA and Marapov, DI and Morozov, SP}, title = {Quantitative parameters of MRI and [18]F-FDG PET/CT in the prediction of breast cancer prognosis and molecular type: an original study.}, journal = {American journal of nuclear medicine and molecular imaging}, volume = {10}, number = {6}, pages = {279-292}, pmid = {33329930}, issn = {2160-8407}, abstract = {The purpose of this work is to evaluate the quantitative parameters of magnetic resonance imaging (MRI), particularly diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) as well as positron-emission tomography, combined with computer tomography (PET/CT), with [18]F-fluorodesoxyglucose, in the prediction of breast cancer molecular type. We studied the correlation between a set of parameters in the invasive ductal carcinoma of the breast, not otherwise specified (IDC-NOS) as it is the most common invasive breast tumor. The parameters were as follows: apparent diffusion coefficient (ADC) in DWI, positive enhancement integral (PEI) in DCE, maximum standardized uptake value (SUVmax) in [18]F-FDG PET/CT, tumor size, grade, and Ki-67 index, level of lymph node metastatic lesions. We also evaluated the probability of a statistically significant difference in mean ADC, PEI, and SUVmax values for patient groups with different Nottingham prognostic index (NPI) and molecular tumor type. Statistically significant correlations between SUVmax, tumor size, and NPI, mean and minimal ADC values with Ki-67 and molecular tumor type were found. The PEI showed a correlation with the NPI risk level and was characterized by a relationship with the magnitude of the predicted NPI risk and regional lymph node involvement. The prognostic model created in our work allows for NPI risk group prediction. The SUVmax, ADC and PEI are non-invasive prognostic markers in the invasive breast cancer of no specific type. The correlation between ADC values and the expression of some tumor receptors can be used for in vivo molecular tumor type monitoring and treatment adjustment.}, } @article {pmid33329538, year = {2020}, author = {Niespolo, C and Johnston, JM and Deshmukh, SR and Satam, S and Shologu, Z and Villacanas, O and Sudbery, IM and Wilson, HL and Kiss-Toth, E}, title = {Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574046}, pmid = {33329538}, issn = {1664-3224}, support = {PG/16/44/32146/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {3' Untranslated Regions ; Animals ; Binding Sites ; Cell Line, Tumor ; Cytokines/*metabolism ; Gene Expression Regulation ; Humans ; Inflammation ; Interleukin-8/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism/*physiology ; Macrophages/*metabolism ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics/*metabolism ; Phenotype ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics/metabolism/physiology ; RNA, Messenger/genetics/metabolism ; }, abstract = {The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3'untranslated region (3'UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple "high confidence" miRNAs potentially binding to the 3'UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3'UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.}, } @article {pmid33329225, year = {2020}, author = {Roth, Y and Plonsky, O and Shalev, E and Erev, I}, title = {On the Value of Alert Systems and Gentle Rule Enforcement in Addressing Pandemics.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {577743}, pmid = {33329225}, issn = {1664-1078}, abstract = {The COVID-19 pandemic poses a major challenge to policy makers on how to encourage compliance to social distancing and personal protection rules. This paper compares the effectiveness of two policies that aim to increase the frequency of responsible health behavior using smartphone-tracking applications. The first involves enhanced alert capabilities, which remove social externalities and protect the users from others' reckless behavior. The second adds a rule enforcement mechanism that reduces the users' benefit from reckless behavior. Both strategies should be effective if agents are expected-value maximizers, risk averse, and behave in accordance with cumulative prospect theory (Tversky and Kahneman, 1992) or in accordance with the Cognitive Hierarchy model (Camerer et al., 2004). A multi-player trust-game experiment was designed to compare the effectiveness of the two policies. The results reveal a substantial advantage to the enforcement application, even one with occasional misses. The enhanced-alert strategy was completely ineffective. The findings align with the small samples hypothesis, suggesting that decision makers tend to select the options that lead to the best payoff in a small sample of similar past experiences. In the current context, the tendency to rely on a small sample appears to be more consequential than other deviations from rational choice.}, } @article {pmid33328559, year = {2020}, author = {Wu, SG and Yang, SP and Zhang, WW and Wang, J and Lian, CL and Chen, YX and He, ZY}, title = {The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {22070}, pmid = {33328559}, issn = {2045-2322}, mesh = {Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; Survival Rate ; }, abstract = {The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.}, } @article {pmid33327281, year = {2020}, author = {Guan, X and Xu, G and Shi, A and Zou, Y and Zhan, Y and Fan, Z and Dong, Y}, title = {Comparison of clinicopathological characteristics and prognosis among patients with pure invasive ductal carcinoma, invasive ductal carcinoma coexisted with invasive micropapillary carcinoma, and invasive ductal carcinoma coexisted with ductal carcinoma in situ: A retrospective cohort study.}, journal = {Medicine}, volume = {99}, number = {50}, pages = {e23487}, pmid = {33327281}, issn = {1536-5964}, mesh = {Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Prognosis ; Retrospective Studies ; }, abstract = {This paper aimed to analyze the clinicopathological characteristics of invasive ductal carcinoma with an invasive micropapillary carcinoma component (IDC + IMPC), invasive ductal carcinoma with a ductal carcinoma in situ component (IDC + DCIS), and compare the clinicopathological characteristics and prognosis to those of IDC.A total of 1713 patients (130 IDC + IMPC cases, 352 IDC + DCIS cases, and 1231 pure IDC cases) who underwent appropriate surgery from June 2011 to September 2017 were retrospectively selected.Compared to the pure IDC and IDC + DCIS patients, the IDC + IMPC patients presented with more aggressive characteristics, such as a higher proportion of vascular invasion (P < .001), fewer progesterone receptor (PR)-positive patients (P < .001), a lower proportion of cases in American Joint Committee on Cancer stage I (P < .001), a higher recurrence risk (P < .001), more deaths (P < .001), and more metastatic cases (P < .001). Compared to the pure IDC and IDC + IMPC patients, the IDC+DCIS patients presented with less aggressive characteristics, such as a higher proportion of estrogen receptor-positive patients (P < .001) and PR-positive patients (P < .001), a lower proportion of cases with nerve invasion (P < .001) and vascular invasion (P < .001), a higher proportion of cases in American Joint Committee on Cancer stage I (P < .001), fewer deaths (P < .001), and fewer metastatic cases (P < .001). The patients with IDC + DCIS had significantly better disease-free survival (DFS) and overall survival (OS) compared to those with pure IDC and IDC + IMPC (P < .001). The patients with IDC + IMPC had significantly worse DFS and OS compared to those with pure IDC and IDC + DCIS (P < .001). In univariate analysis, the presence of an IMPC component in IDC (P = .007), estrogen receptor status (P = .05), and PR status (P = .003) were factors associated with OS. In multivariate analysis, coexisting IMPC (P = .04) was the only independent prognostic factor associated with OS.Compared to IDC and IDC + DCIS, IDC + IMPC had more aggressive characteristics and significantly worse DFS and OS. Compared to IDC and IDC + IMPC, IDC + DCIS had less aggressive characteristics and significantly better DFS and OS.}, } @article {pmid33316685, year = {2021}, author = {Zhang, J and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response rates for breast cancer stages as a predictor of outcomes in patients receiving neoadjuvant chemotherapy followed by breast-conserving surgery.}, journal = {Surgical oncology}, volume = {36}, number = {}, pages = {91-98}, doi = {10.1016/j.suronc.2020.11.015}, pmid = {33316685}, issn = {1879-3320}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*pathology/therapy ; Chemotherapy, Adjuvant/*methods ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Prognosis ; Young Adult ; }, abstract = {PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.

PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients' PRRs; other independent predictors were controlled for or stratified in the analysis.

RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13-0.56), 0.36 (0.15-0.85), and 0.15 (0.08-0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35-0.89), 0.91 (0.62-0.96), and 0.63 (0.43-0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06-2.24), 1.08 (1.03-1.82), and 1.19 (1.07-2.01) for all-cause mortality, LRR, and DM, respectively.

CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.}, } @article {pmid33313192, year = {2020}, author = {Jing, N and Ma, MW and Gao, XS and Liu, JT and Gu, XB and Zhang, M and Zhao, B and Wang, Y and Wang, XL and Jia, HX}, title = {Development and validation of a prognostic nomogram for patients with triple-negative breast cancer with histology of infiltrating duct carcinoma.}, journal = {Annals of translational medicine}, volume = {8}, number = {21}, pages = {1447}, pmid = {33313192}, issn = {2305-5839}, abstract = {BACKGROUND: The purpose of this study was to develop prognostic nomograms from a cohort of patients with triple-negative breast cancer (TNBC) with histology of infiltrating duct carcinoma (IDC) by correlating their clinical and pathological parameters with the rates of disease-free survival (DFS) and overall survival (OS).

METHODS: We retrospectively analyzed TNBC patients with histology of IDC at our institution between 2009 and 2012. Age, family history, menopausal status, surgery type, T stage, N stage, histological grade, vascular invasion, perineural invasion, cytokeratin 5/6 status, Ki-67 expression, and epithelial cadherin (E-cadherin) status were analyzed. Predictors were used in multivariable logistic regression analysis to develop a nomogram to predict DFS and OS rates. The nomograms were then subjected to internal validation, with external validation of the nomogram for predicting OS using separate cohorts of TNBC patients known from the Cancer Genome Atlas (TCGA) database. Using the concordance index (C-index) with calibration curves, the predictive accuracy and discriminative ability were calculated.

RESULTS: A total of 242 eligible TNBC patients were included for analysis. The median follow-up time was 70.73 months. Of the patients, 32.6%, 42.6%, and 24.8% had stage I, II, and III disease, respectively. The 3- and 5-year survival rates were 81.0% and 76.5% for DFS, and 86.5% and 81.1%, for OS, respectively. Age, T stage, N stage, and E-cadherin status were found to be risk factors. The nomograms based on those risk factors accurately predicted the 3- and 5-year survival rates. The C-index was 0.798 and 0.821 for DFS and OS, respectively. Besides, the nomogram for OS showed relatively reliable performance in stratifying different risk groups of patients in training and validation cohorts identified from the TCGA database. The C-index reached 0.843. DFS validation was not completed, as there was insufficient data.

CONCLUSIONS: Using clinicopathological information, we produced a prognostic nomogram that accurately predicts the 3- and 5-year DFS and OS for patients with TNBC with histology of IDC. More external confirmation is required.}, } @article {pmid33312887, year = {2020}, author = {Aliyu, UM and Musa, AA}, title = {Assessment of breast cancer immunohistochemistry and tumor characteristics in Nigeria.}, journal = {World journal of clinical oncology}, volume = {11}, number = {11}, pages = {935-944}, pmid = {33312887}, issn = {2218-4333}, abstract = {BACKGROUND: Female breast cancer is the leading type of cancer worldwide with an incidence of approximately 2.1 million in 2018. Hormone receptor status plays a vital role in its management.

AIM: To determine the molecular expression pattern of biomarkers in breast cancer and their correlation with tumor variables.

METHODS: This prospective study was designed to analyze expression patterns of estrogen receptor(ER), progesterone receptor (PR) and human epidermal growth factor receptor(HER2/neu) in breast cancer patients. The dataset has been taken from the Department of Radiotherapy and Oncology of Usmanu Danfodiyo University Teaching Hospital Sokoto, Nigeria from 1 January 2015 to 2 December 2019. The dataset had 259 records and 7 attributes. SPSS version 23.0 for statistical analysis was used. The data analyzed demographic and other clinicopathological characteristics as categorical variables. The mean and standard deviation were determined for the quantitative variable.

RESULTS: A total of 259 breast cancer cases were included in the study. The mean age was 48.3 ± 11.0, with an age range of 26-80 years and a median age of 46 years. The morphological categories were invasive ductal carcinoma 258 (99.6%) and invasive lobular carcinoma 1 (0.4%). ER, positivity increased in 73 patients (50%) under the age of 50 years, as well as PR positivity increased in 34 patients (23.6%) under the age of 50 years. HER/2neupositivity decreased in 8 patients (5.6%) under the age of 50 years. Hormonal receptors were statistically significant with clinicopathological characteristics (P < 0.05).

CONCLUSION: Our study showed that ER, PR and HER2/neuexpression had a strong correlation with age, tumor grade, tumor size and lymph node status. Hence, hormone receptor assessment is highly recommended because of its significance in clinical management and prognostication.}, } @article {pmid33309471, year = {2021}, author = {Declemy, A and Chesnel, C and Charlanes, A and Le Breton, F and Sheikh Ismael, S and Amarenco, G}, title = {Short-term reproducibility of cystometry in multiple sclerosis patients.}, journal = {Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie}, volume = {31}, number = {3}, pages = {169-174}, doi = {10.1016/j.purol.2020.11.012}, pmid = {33309471}, issn = {1166-7087}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/*physiopathology ; Prospective Studies ; Reproducibility of Results ; Urinary Bladder/*physiopathology ; }, abstract = {OBJECTIVE: To assess the reproducibility of detrusor activity cystometric pattern in multiple sclerosis (MS) patients, which is poorly documented in the medical literature, by means of successive filling.

METHODS: We conducted a prospective study in MS patients; cystometry was repeated twice at 5minutes of interval if a detrusor overactivity before 300mL of filling was observed. Thus, 3 successive cystometries were analysed. The following characteristics were recorded: detrusor maximum pressure (Pmax), volume at the first involuntary detrusor contraction (IDC), maximum cystometric capacity (MCC), pressure at the first IDC, the existence of an overactive detrusor classified as phasic or terminal.

RESULTS: We included 31 patients (19 women and 12 men); only 6 patients were naïve-treatment, the mean EDSS was: 5.3 (±1.6) and the mean age was 48.4 (±12.5) years. All the patients had an overactive detrusor for each cystometry. The reproducibility was good for all the parameters (range ICC between 0.7 and 0.83).

CONCLUSION: Quantitative and qualitative cystometric data have a good reproducibility in MS patients with detrusor overactivity before 300mL of filling.

LEVEL OF PROOF: 3.}, } @article {pmid33306310, year = {2020}, author = {Wanderley, J and Buffolo, E and Mendonça, JT}, title = {Brazilian Academy of Cardiovascular Surgery: From Idea to Reality.}, journal = {Brazilian journal of cardiovascular surgery}, volume = {35}, number = {6}, pages = {IV-VI}, pmid = {33306310}, issn = {1678-9741}, mesh = {*Academies and Institutes ; Brazil ; *Cardiovascular Surgical Procedures ; }, } @article {pmid33306068, year = {2020}, author = {Halbony, H and Salman, K and Alqassieh, A and Albrezat, M and Hamdan, A and Abualhaija'a, A and Alsaeidi, O and Masad Melhem, J and Sagiroglu, J and Alimoglu, O}, title = {Breast cancer epidemiology among surgically treated patients in Jordan: A retrospective study.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {34}, number = {}, pages = {73}, pmid = {33306068}, issn = {1016-1430}, abstract = {Background: Multiple risk factors contribute to the development of breast cancer, including age, positive family history, early menarche, late menopause and the strongest factor being female gender. In this study, we aimed to investigate the proportion of breast cancer patients with certain risk factors, the prevalence of each cancer type, in addition to the surgical procedures performed. Methods: The medical records of patients diagnosed with breast cancer from January 2010 to November 2015 were evaluated retrospectively regarding demographics, breast cancer risk factors, comorbidities, diagnostic methods, tumor location, cancer type and stage, pathological findings, tumor markers, harvested lymph nodes and the types of surgical procedures. The collected data were statistically analyzed as number, mean, and frequency as percentages. Cases with deficient medical records were excluded from the analysis of certain parameters. Results: The sample consisted of 120 patients, 118 (98.3%) of whom were women. The mean age was 56.5±12.0 years. The most common diagnostic method at presentation was self-exam in 93.3% of patients. Invasive ductal carcinoma was the most common type of tumor (80.0%). The pathological stages could be determined for only 106 patients, and 26 patients (24.5%) were at stage 1 disease, 45 patients (42.5%) were at stage 2 whereas 34 patients (32.1%) were at stage 3. According to the results of pathological examinations, 72.6% (85 patients) of the cases were estrogen receptor positive, 61.2% (71 patients) were progesterone receptor positive while 24.8% (27 patients) were HER positive. Modified radical mastectomy (MRM) was performed in 52 (43.3%) patients and wide local excision (WLE) was preferred in 46 (38.3%) cases. Conclusion: Advanced age, positive family history, and prolonged estrogen exposure were remarkable in the majority of patients. Moreover, the most common type of breast cancer was invasive ductal carcinoma, and around half of the patients presented at stage 2 disease. Modified radical mastectomy and WLE were the most commonly performed surgical procedures.}, } @article {pmid33302909, year = {2020}, author = {Desa, DE and Strawderman, RL and Wu, W and Hill, RL and Smid, M and Martens, JWM and Turner, BM and Brown, EB}, title = {Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1217}, pmid = {33302909}, issn = {1471-2407}, support = {R21 CA208921/CA/NCI NIH HHS/United States ; W81XWH-15-1-0040//U.S. Department of Defense/ ; W81XWH-17-1-0011//U.S. Department of Defense/ ; R21CA208921//Foundation for the National Institutes of Health/ ; }, mesh = {Breast Neoplasms/chemistry/*ultrastructure ; Carcinoma, Ductal, Breast/chemistry/secondary/*ultrastructure ; *Estrogens ; Female ; Fibrillar Collagens/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; *Neoplasm Metastasis ; Neoplasm Proteins/*ultrastructure ; Neoplasms, Hormone-Dependent/chemistry/*ultrastructure ; Prognosis ; Risk ; *Second Harmonic Generation Microscopy ; Single-Blind Method ; Stromal Cells/chemistry/ultrastructure ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Metastases are the leading cause of breast cancer-related deaths. The tumor microenvironment impacts cancer progression and metastatic ability. Fibrillar collagen, a major extracellular matrix component, can be studied using the light scattering phenomenon known as second-harmonic generation (SHG). The ratio of forward- to backward-scattered SHG photons (F/B) is sensitive to collagen fiber internal structure and has been shown to be an independent prognostic indicator of metastasis-free survival time (MFS). Here we assess the effects of heterogeneity in the tumor matrix on the possible use of F/B as a prognostic tool.

METHODS: SHG imaging was performed on sectioned primary tumor excisions from 95 untreated, estrogen receptor-positive, lymph node negative invasive ductal carcinoma patients. We identified two distinct regions whose collagen displayed different average F/B values, indicative of spatial heterogeneity: the cellular tumor bulk and surrounding tumor-stroma interface. To evaluate the impact of heterogeneity on F/B's prognostic ability, we performed SHG imaging in the tumor bulk and tumor-stroma interface, calculated a 21-gene recurrence score (surrogate for OncotypeDX®, or S-ODX) for each patient and evaluated their combined prognostic ability.

RESULTS: We found that F/B measured in tumor-stroma interface, but not tumor bulk, is prognostic of MFS using three methods to select pixels for analysis: an intensity threshold selected by a blinded observer, a histogram-based thresholding method, and an adaptive thresholding method. Using both regression trees and Random Survival Forests for MFS outcome, we obtained data-driven prediction rules that show F/B from tumor-stroma interface, but not tumor bulk, and S-ODX both contribute to predicting MFS in this patient cohort. We also separated patients into low-intermediate (S-ODX < 26) and high risk (S-ODX ≥26) groups. In the low-intermediate risk group, comprised of patients not typically recommended for adjuvant chemotherapy, we find that F/B from the tumor-stroma interface is prognostic of MFS and can identify a patient cohort with poor outcomes.

CONCLUSIONS: These data demonstrate that intratumoral heterogeneity in F/B values can play an important role in its possible use as a prognostic marker, and that F/B from tumor-stroma interface of primary tumor excisions may provide useful information to stratify patients by metastatic risk.}, } @article {pmid33297647, year = {2020}, author = {Chen, QX and Zhang, YX and Li, K and Dong, H and Xu, H and Lin, GZ and Ren, ZF}, title = {[Characteristics and prognosis of female breast cancer in Guangzhou, 2008-2017].}, journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi}, volume = {41}, number = {11}, pages = {1831-1835}, doi = {10.3760/cma.j.cn112338-20191012-00731}, pmid = {33297647}, issn = {0254-6450}, mesh = {Age Distribution ; Aged ; *Breast Neoplasms/pathology/therapy ; China/epidemiology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate/trends ; }, abstract = {Objective: To describe the distributions of demographic and clinic pathological characteristics and relations with survival on female breast cancer patients in Guangzhou from 2008 to 2017. Methods: The baseline information of the subjects was obtained from the Guangzhou cancer registry and the outcomes were from the Cancer Follow-up System of Guangzhou. Kaplan-Meier was used to calculate the 1-, 3-, 5-year overall survival rates. Univariate and multivariate Cox proportional hazards regression models were used to identify the factors related to the overall survival. Results: Among the 12 465 breast cancer patients recruited in the study, the average age at diagnosis was 53.9 years old, with those aged 45 to 54 making up the largest proportion (43.9%). Only 15.6% of the patients had college or above degrees. Patients with normal BMI accounted for 78.2%. Most of the patients (90.0%) had received surgical treatment. Invasive ductal carcinoma appeared the most common histologic type, accounting for 82.3%. Among the 2 640 patients diagnosed in the four large hospitals, clinical stages 0-Ⅰ, Ⅱ, Ⅲ and Ⅳ accounted for 35.0%, 44.8%, 17.2% and 3.0%, respectively. The proportions of ER-positive, PR-positive and HER-2 positive breast cancer were 79.5%, 70.8%, and 19.2%, respectively. In terms of subtypes, Luminal B was the most common one, accounted for 53.3%. The 1-, 3- and 5-year overall survival rates were 99.0%, 95.3% and 92.1%, respectively. Results from the multivariate analysis indicated that factors as: age over 55 years old at diagnosis, advanced TNM stage, ER negative, PR negative, Luminal B subtype and triple-negative subtype were associated with poorer prognosis. Conclusions: Compared with the previous hospital-based studies in China, this population-based study revealed that the proportions of patients with advanced age, early clinical stage or ER positive breast cancer were relatively high and the overall survival rate for breast cancer was higher than that in the previous studies. Relationships between characteristics and prognosis of breast cancer were consistent with the previous findings.}, } @article {pmid33289978, year = {2020}, author = {Roy, M and Teshome, M and Damodaran, S and Sahin, AA and Khazai, L and Arribas, E and Candelaria, RP and Scoggins, ME and Lane, DL and Giordano, SH and Albarracin, CT and Prieto, VG and Nagarajan, P}, title = {Male Mammary Paget Disease: A Tale of 2 Contrasting Cases.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {12}, pages = {981-985}, doi = {10.1097/DAD.0000000000001799}, pmid = {33289978}, issn = {1533-0311}, mesh = {Aged, 80 and over ; Breast Neoplasms, Male/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Paget's Disease, Mammary/diagnostic imaging/*pathology/surgery ; Treatment Outcome ; }, abstract = {Mammary Paget disease (MPD) comprises 1.45% all male breast cancers, compared with only 0.68% of all female breast cancers. Patients usually present in the fifth and sixth decades of life with ulceration, eczematous changes, discharge, bleeding, itching, and induration of the nipple and areola. Typically, there is a delay in definitive diagnosis and treatment from the onset of symptoms because most patients are initially treated for a rash. At the time of diagnosis, about half of the patients may have palpable breast mass, positive lymph nodes, or both. In this article, we present 2 cases of male MPD representing the extremes of clinical, radiologic, and histopathologic spectrum of the disease. One patient presented with a rash of the nipple of several months duration without an underlying lesion, whereas the other presented with sensitivity and pain of the nipple for 1 year and an underlying mass. Biopsies were diagnostic of MPD in both cases, and definitive surgery revealed an underlying ductal carcinoma in situ in the first case and an invasive ductal carcinoma in the second, highlighting the importance of early biopsy to initiate appropriate management.}, } @article {pmid33285997, year = {2020}, author = {Zhang, Y and Liu, R}, title = {Robust Power Optimization for Downlink Cloud Radio Access Networks with Physical Layer Security.}, journal = {Entropy (Basel, Switzerland)}, volume = {22}, number = {2}, pages = {}, pmid = {33285997}, issn = {1099-4300}, abstract = {Since the cloud radio access network (C-RAN) transmits information signals by jointly transmission, the multiple copies of information signals might be eavesdropped on. Therefore, this paper studies the resource allocation algorithm for secure energy optimization in a downlink C-RAN, via jointly designing base station (BS) mode, beamforming and artificial noise (AN) given imperfect channel state information (CSI) of information receivers (IRs) and eavesdrop receivers (ERs). The considered resource allocation design problem is formulated as a nonlinear programming problem of power minimization under the quality of service (QoS) for each IR, the power constraint for each BS, and the physical layer security (PLS) constraints for each ER. To solve this non-trivial problem, we first adopt smooth ℓ 0 -norm approximation and propose a general iterative difference of convex (IDC) algorithm with provable convergence for a difference of convex programming problem. Then, a three-stage algorithm is proposed to solve the original problem, which firstly apply the iterative difference of convex programming with semi-definite relaxation (SDR) technique to provide a roughly (approximately) sparse solution, and then improve the sparsity of the solutions using a deflation based post processing method. The effectiveness of the proposed algorithm is validated with extensive simulations for power minimization in secure downlink C-RANs.}, } @article {pmid33284403, year = {2020}, author = {Katano, K and Yoshimitsu, Y and Kyuno, T and Haba, Y and Maeda, T and Kitamura, S}, title = {Temporary spontaneous regression of male breast cancer: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {311}, pmid = {33284403}, issn = {2198-7793}, abstract = {BACKGROUND: Spontaneous regression (SR) of a malignant tumor is the partial or complete disappearance of primary or metastatic tumor tissue in the absence of treatment, which can be temporary or permanent. Here, we report an extremely rare case of male breast cancer that exhibited temporary SR followed by reappearance 8 months after tumor disappearance.

CASE PRESENTATION: A 70-year-old man presented at our hospital with a primary complaint of pain and a lump in his left breast. Ultrasonography revealed a hypoechoic lesion measuring 12 mm × 10 mm × 8 mm. Fine-needle aspiration cytology revealed numerous necrotic and degenerated cells and few sheet-like clusters of atypical ductal epithelial cells. The atypical cells had mildly enlarged nuclei with nucleoli, were focally overlapped and formed tubular patterns. The cytological diagnosis indicated a suspicion of malignancy. Core needle biopsy (CNB) revealed necrotic and degenerated cells with microcalcification. The pathological diagnosis was indeterminate because there was no area of viable atypical cells. An excisional biopsy of the left breast lesion was scheduled one month later. However, it was difficult to detect the tumor during physical examination and ultrasonography performed 1 month after the patient's first visit. The operation was canceled, and the patient received follow-up observation. After 8 months of follow-up, ultrasonography and computed tomography (CT) revealed reappearance of a 0.6-cm-diameter breast tumor in the same place. CNB was performed again and revealed invasive ductal carcinoma. A total mastectomy with sentinel lymph node biopsy was performed 13 months after the first tumor disappeared. Histopathological examination revealed invasive cribriform carcinoma without sentinel lymph node metastasis. The patient did not have any complications, and adjuvant therapy with tamoxifen was started. The patient was alive without recurrence 7 months after surgery.

CONCLUSIONS: Temporary SR followed by tumor reappearance can occur in breast cancer cases, and it is important to follow patients even if their breast tumor has seemingly disappeared. When breast tumors disappear without treatment, clinicians must be aware of the possibility of SR of cancer and should follow the patient for early detection of tumor reappearance.}, } @article {pmid33283376, year = {2020}, author = {Crown, A and Carlson, E and Rocha, FG and Grumley, JW}, title = {Oncoplastic breast-conserving therapy and intraoperative radiotherapy for management of carcinoma in situ of the breast: A single-center experience.}, journal = {The breast journal}, volume = {26}, number = {12}, pages = {2391-2394}, doi = {10.1111/tbj.14093}, pmid = {33283376}, issn = {1524-4741}, mesh = {Breast ; *Breast Neoplasms/radiotherapy/surgery ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating/radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Neoplasm Recurrence, Local/surgery ; Radiotherapy, Adjuvant ; }, abstract = {Intraoperative radiation therapy (IORT) has been shown to reduce local recurrence rates among women with early-stage invasive ductal carcinoma, but data regarding its use among women with in situ carcinoma are limited. In this single-institution study, 50 women with in situ carcinoma were treated with oncoplastic breast-conserving surgery (OPS) and single-dose IORT. All 50 patients had "no tumor on ink," but 9 (16%) had margins < 2 mm and required additional therapy. No local recurrences were observed after a median follow-up of 46 months. Single-dose IORT is an efficacious treatment for well-selected patients with DCIS.}, } @article {pmid33281649, year = {2020}, author = {Leshem, R and Icht, M and Bentzur, R and Ben-David, BM}, title = {Processing of Emotions in Speech in Forensic Patients With Schizophrenia: Impairments in Identification, Selective Attention, and Integration of Speech Channels.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {601763}, pmid = {33281649}, issn = {1664-0640}, abstract = {Individuals with schizophrenia show deficits in recognition of emotions which may increase the risk of violence. This study explored how forensic patients with schizophrenia process spoken emotion by: (a) identifying emotions expressed in prosodic and semantic content separately, (b) selectively attending to one speech channel while ignoring the other, and (c) integrating the prosodic and the semantic channels, compared to non-clinical controls. Twenty-one forensic patients with schizophrenia and 21 matched controls listened to sentences conveying four emotions (anger, happiness, sadness, and neutrality) presented in semantic or prosodic channels, in different combinations. They were asked to rate how much they agreed that the sentences conveyed a predefined emotion, focusing on one channel or on the sentence as a whole. Forensic patients with schizophrenia performed with intact identification and integration of spoken emotions, but their ratings indicated reduced discrimination, larger failures of selective attention, and under-ratings of negative emotions, compared to controls. This finding doesn't support previous reports of an inclination to interpret social situations in a negative way among individuals with schizophrenia. Finally, current results may guide rehabilitation approaches matched to the pattern of auditory emotional processing presented by forensic patients with schizophrenia, improving social interactions and quality of life.}, } @article {pmid33279405, year = {2021}, author = {Jafferbhoy, SF and Goussous, G and Chandarana, M and Salehi-Bird, S and Mohd-Isa, Z and Gunning, E and Bajwa, S and Hammond, L and Marla, S and Narayanan, S and Soumian, S}, title = {Impact of Preoperative MRI in Invasive Ductal Carcinoma With Lobular Features on Core Biopsy.}, journal = {Clinical breast cancer}, volume = {21}, number = {3}, pages = {e194-e198}, doi = {10.1016/j.clbc.2020.08.007}, pmid = {33279405}, issn = {1938-0666}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Ultrasonography, Mammary/methods ; }, abstract = {BACKGROUND: Invasive breast cancer is comprised of a wide spectrum of histological types with different clinical presentations, imaging characteristics, and behaviors. Almost 10% of breast cancers with predominantly invasive ductal features have lobular components on core biopsy at primary diagnosis. Although the role of magnetic resonance imaging (MRI) in patients with purely lobular cancers is well-established, it is not clear if preoperative MRI is indicated in ductal cancer with lobular features. The aim of this study was to assess the role of preoperative MRI in patients with invasive ductal cancers with lobular features on core biopsy.

MATERIALS AND METHODS: Data regarding patients with lobular features on core biopsy who underwent a preoperative MRI from January 2015 to December 2017 were retrospectively identified and analyzed. Imaging findings, additional investigations, and changes in treatment plans following the MRI scan were reviewed.

RESULTS: The study included 120 patients, of whom 42 (35%) patients required a second-look ultrasound. Following a repeat ultrasound scan, 25 breasts and 4 axillae were biopsied. Thirty-eight percent of the breast biopsies and 50% of the axillary biopsies were malignant. Based on MRI findings, treatment plans changed in 22.5% of patients. MRI size was concordant with the histological size in 58.3% of cases, and MRI was accurate in 90% of patients in detecting multifocal disease requiring mastectomy. The majority of patients with changes in the management plans had mixed ductal and lobular cancer on final histology.

CONCLUSION: This study has demonstrated that MRI picks up additional malignancies and changes management plans in patients with lobular features on core biopsy and should be considered in the preoperative workup.}, } @article {pmid33278619, year = {2021}, author = {Hadano, Y and Kakuma, T and Matsumoto, T and Ishibashi, K and Isoda, M and Yasunaga, H}, title = {Reduction of 30-day death rates from Staphylococcus aureus bacteremia by mandatory infectious diseases consultation: Comparative study interventions with and without an infectious disease specialist.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {103}, number = {}, pages = {308-315}, doi = {10.1016/j.ijid.2020.11.199}, pmid = {33278619}, issn = {1878-3511}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/microbiology/mortality ; Case Management ; Female ; Hospitals ; Humans ; Japan ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Specialization ; Staphylococcal Infections/*drug therapy/microbiology ; Staphylococcus aureus/*drug effects ; Treatment Outcome ; }, abstract = {OBJECTIVES: Most Japanese hospitals need to keep to higher Staphylococcus aureus bacteremia (SAB) quality-of-care indicators (QCIs) and create strategies that can maximize the effect of these QCIs with only a small number of infectious disease specialists. This study aimed to evaluate the clinical outcomes of patients with SAB before and after the enhancement of the mandatory infectious disease consultations (IDCs).

METHODS: This retrospective study was conducted at a tertiary care hospital in Japan. The primary outcome was the 30-day mortality between each period. A generalized structural equation model was employed to examine the effect of the mandatory IDC enhancement on 30-day mortality among patients with SAB.

RESULTS: A total of 114 patients with SAB were analyzed. The 30-day all-cause mortality differed significantly between the two periods (17.3% vs. 4.8%, P = 0.02). Age, three-QCI point ≥ 1, and Pitt bacteremia score ≥ 3 were the significant risk factors for 30-day mortality. The intervention was also significantly associated with improved adherence to QCIs.

CONCLUSION: Mandatory IDCs for SAB improved 30-day mortality and adherence to QCIs after the intervention. In Japan, improving the quality of management in patients with SAB should be an important target.}, } @article {pmid33276203, year = {2021}, author = {Kim, G and Mercaldo, S and Bahl, M}, title = {Impact of digital breast tomosynthesis (DBT) on finding types leading to true-positive and false-positive examinations.}, journal = {Clinical imaging}, volume = {71}, number = {}, pages = {155-159}, doi = {10.1016/j.clinimag.2020.10.046}, pmid = {33276203}, issn = {1873-4499}, mesh = {Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging ; *Calcinosis ; *Choristoma ; Early Detection of Cancer ; Humans ; Mammography ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate the frequencies of finding types with combined digital breast tomosynthesis (DBT) and digital mammography (DM) leading to true-positive (TP) and false-positive (FP) examinations.

MATERIALS AND METHODS: Consecutive screening mammograms at an academic medical center from March 2008 to February 2011 (DM group) and from January 2013 to December 2017 (DBT/DM group) were retrospectively reviewed. Multivariable logistic regression models were used to compare the proportions of mammographic finding types leading to TP and FP examinations between the two groups.

RESULTS: The DM group had 554 TP and 7278 FP examinations, and the DBT/DM group had 1271 TP and 14,544 FP examinations. The finding type of calcifications led to a lower proportion of TP examinations in the DBT/DM than DM group (34.3% versus 47.7%, p < 0.001) but also a lower proportion of FP examinations (18.7% versus 21.7%, p < 0.001). Mass led to a higher proportion of TP examinations in the DBT/DM than DM group (5.7% versus 1.3%, p < 0.001) but also a higher proportion of FP examinations (4.6% versus 0.3%, p < 0.001). Asymmetry led to a higher proportion of TP examinations in the DBT/DM than DM group (58.3% versus 50.4%, p = 0.03) and a lower proportion of FP examinations (75.9% versus 77.6%, p < 0.001). Architectural distortion led a similar proportion of TP examinations in the DBT/DM and DM groups (1.7% versus 0.7%, p = 0.12) but a higher proportion of FP examinations (0.8% versus 0.4%, p = 0.007).

CONCLUSIONS: Mammographic findings leading to TP and FP examinations have shifted with the addition of DBT to DM.}, } @article {pmid33274157, year = {2020}, author = {Hashmi, AA and Iftikhar, SN and Munawar, S and Shah, A and Irfan, M and Ali, J}, title = {Encapsulated Papillary Carcinoma of Breast: Clinicopathological Features and Prognostic Parameters.}, journal = {Cureus}, volume = {12}, number = {10}, pages = {e11282}, pmid = {33274157}, issn = {2168-8184}, abstract = {Introduction Encapsulated papillary carcinoma (EPC) is a rare malignant papillary breast tumor that, despite a lack of distinct myoepithelial layer, is considered an in situ carcinoma unless associated with a frank invasive component. Data regarding clinicopathologic features of rare breast tumors like EPC are especially scarce. Therefore, in this study, we evaluated the clinicopathologic features of EPC and performed a clinicopathological comparison with conventional invasive ductal carcinoma (IDC). Methods It was a retrospective study conducted in the Department of Pathology, Liaquat National Hospital and Medical College, from January 2013 to December 2019 over a period of seven years. During this period, 16 cases were diagnosed as EPC, and 634 cases were labeled as IDC. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) immunohistochemical (IHC) stains were performed on both EPC and IDC cases. Moreover, myoepithelial IHC stains were performed on all cases of EPC. Clinicopathologic features of EPC were compared with IDC. Results The mean age of the EPC patients was 51.81±13.94 years, with a mean tumor size of 2.97±2.46 cm. The majority of cases were grade II, and axillary metastasis was present in 18.8% of cases. About 56.3% of cases were in situ, and 43.8% showed foci of invasion in the form of IDC. Recurrence was noted in 12.5% of cases with a survival rate of 93.8%. ER, PR, and HER2/neu positivity was noted in 81.3%, 75%, and 12.5% cases, respectively. EPC was significantly noted to have lower tumor grade and pathological T-stage than IDC. Similarly, a lower frequency of axillary metastasis was noted in EPC than IDC. Conclusion EPC is a rare distinct subtype of papillary breast tumors with overall good survival and low recurrence rate. Compared to IDC, we found EPC to be associated with better prognostic parameters such as lower tumor grade and T-stage and lower frequency of axillary metastasis.}, } @article {pmid33270144, year = {2021}, author = {Cheung, SM and Husain, E and Mallikourti, V and Masannat, Y and Heys, S and He, J}, title = {Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic resonance spectroscopy.}, journal = {European radiology}, volume = {31}, number = {6}, pages = {3703-3711}, pmid = {33270144}, issn = {1432-1084}, support = {RS2015 004//Friends of ANCHOR/ ; }, mesh = {Adult ; Aged ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Lipids ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {OBJECTIVES: Despite improved survival due to new treatments, the 10-year survival rate in patients with breast cancer is approximately 75%. Lymphovascular invasion (LVI), a prognostic marker independent from histological grade and stage, can only be fully determined at final histological examination. Lipid composition is deregulated in tumour via de novo lipogenesis, with alteration in lipogenic genes in LVI. We hypothesise alteration in lipid composition derived from novel non-invasive spectroscopy method is associated with LVI positivity.

METHODS: Thirty female patients (age 39-78) with invasive ductal carcinoma were enrolled, with 13 LVI negative and 17 LVI positive. Saturated, monounsaturated, polyunsaturated fatty acids and triglycerides (SFA, MUFA, PUFA and TRG) were quantified from ex vivo breast tumours freshly excised from patients on a 3 T clinical MRI scanner, and proliferative activity marker Ki-67 and serotonin derived histologically.

RESULTS: There were significantly lower MUFA (p = 0.0189) in LVI positive (median: 0.37, interquartile range (IQR): 0.25-0.64) than negative (0.63, 0.49-0.96). There were significantly lower TRG (p = 0.0226) in LVI positive (1.32, 0.95-2.43) than negative (2.5, 1.92-4.15). There was no significant difference in SFA (p = 0.6009) or PUFA (p = 0.1641). There was no significant correlation between lipid composition against Ki-67 or serotonin, apart from a borderline negative correlation between PUFA and serotonin (r = - 0.3616, p = 0.0496).

CONCLUSION: Lipid composition might provide a biomarker to study lymphovascular invasion in breast cancer.

KEY POINTS: • Monounsaturated fatty acids in lymphovascular invasion (LVI) positive invasive breast carcinoma were significantly lower than that in LVI negative. • Triglycerides in LVI positive invasive breast carcinoma were significantly lower than that in LVI negative. • Lipid composition from MR spectroscopy reflects the rate of de novo lipogenesis and provides a potential biomarker independent from histological grade and stage.}, } @article {pmid33267867, year = {2020}, author = {Fredolini, C and Pathak, KV and Paris, L and Chapple, KM and Tsantilas, KA and Rosenow, M and Tegeler, TJ and Garcia-Mansfield, K and Tamburro, D and Zhou, W and Russo, P and Massarut, S and Facchiano, F and Belluco, C and De Maria, R and Garaci, E and Liotta, L and Petricoin, EF and Pirrotte, P}, title = {Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {135}, pmid = {33267867}, issn = {1465-542X}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Biopsy ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/blood/*diagnosis ; Carcinoma, Ductal, Breast/blood/*diagnosis/pathology ; Case-Control Studies ; Cohort Studies ; Early Detection of Cancer/*methods ; Extracellular Matrix Proteins/*blood/chemistry ; Female ; Humans ; Male ; Mammography ; Middle Aged ; Nanoparticles/chemistry ; Proteomics/methods ; }, abstract = {BACKGROUND: The lack of specificity and high degree of false positive and false negative rates when using mammographic screening for detecting early-stage breast cancer is a critical issue. Blood-based molecular assays that could be used in adjunct with mammography for increased specificity and sensitivity could have profound clinical impact. Our objective was to discover and independently verify a panel of candidate blood-based biomarkers that could identify the earliest stages of breast cancer and complement current mammographic screening approaches.

METHODS: We used affinity hydrogel nanoparticles coupled with LC-MS/MS analysis to enrich and analyze low-abundance proteins in serum samples from 20 patients with invasive ductal carcinoma (IDC) breast cancer and 20 female control individuals with positive mammograms and benign pathology at biopsy. We compared these results to those obtained from five cohorts of individuals diagnosed with cancer in organs other than breast (ovarian, lung, prostate, and colon cancer, as well as melanoma) to establish IDC-specific protein signatures. Twenty-four IDC candidate biomarkers were then verified by multiple reaction monitoring (LC-MRM) in an independent validation cohort of 60 serum samples specifically including earliest-stage breast cancer and benign controls (19 early-stage (T1a) IDC and 41 controls).

RESULTS: In our discovery set, 56 proteins were increased in the serum samples from IDC patients, and 32 of these proteins were specific to IDC. Verification of a subset of these proteins in an independent cohort of early-stage T1a breast cancer yielded a panel of 4 proteins, ITGA2B (integrin subunit alpha IIb), FLNA (Filamin A), RAP1A (Ras-associated protein-1A), and TLN-1 (Talin-1), which classified breast cancer patients with 100% sensitivity and 85% specificity (AUC of 0.93).

CONCLUSIONS: Using a nanoparticle-based protein enrichment technology, we identified and verified a highly specific and sensitive protein signature indicative of early-stage breast cancer with no false positives when assessing benign and inflammatory controls. These markers have been previously reported in cell-ECM interaction and tumor microenvironment biology. Further studies with larger cohorts are needed to evaluate whether this biomarker panel improves the positive predictive value of mammography for breast cancer detection.}, } @article {pmid33263939, year = {2021}, author = {D'Alfonso, TM and Pareja, F and Da Cruz Paula, A and Vahdatinia, M and Gazzo, A and Ferrando, L and da Silva, EM and Cheng, E and Sclafani, L and Chandarlapaty, S and Zhang, H and Hoda, SA and Wen, HY and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma.}, journal = {The journal of pathology. Clinical research}, volume = {7}, number = {2}, pages = {113-120}, pmid = {33263939}, issn = {2056-4538}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/complications/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; *DNA Copy Number Variations ; DNA Mutational Analysis ; Female ; Humans ; Mutation ; Papilloma/complications/diagnosis/*genetics/pathology ; Exome Sequencing ; }, abstract = {Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.}, } @article {pmid33262909, year = {2020}, author = {Hashmi, AA and Iftikhar, SN and Haider, R and Haider, R and Irfan, M and Ali, J}, title = {Solid Papillary Carcinoma of Breast: Clinicopathologic Comparison With Conventional Ductal Carcinoma of Breast.}, journal = {Cureus}, volume = {12}, number = {10}, pages = {e11172}, pmid = {33262909}, issn = {2168-8184}, abstract = {Introduction Solid papillary carcinoma (SPC) is a distinct rare subtype of breast tumour that often exhibits a neuroendocrine differentiation. Due to the rarity of these tumours, few studies have assessed the clinicopathological features of these tumours. Therefore, in this study, we evaluated the clinical and pathological profiles of SPC and compared the pathologic features with conventional invasive ductal carcinoma (IDC) in our population. Methods It was a retrospective cross-sectional study conducted at Liaquat National Hospital and Medical College from January 2013 until December 2019 over seven years. Cases with histological diagnosis of SPC and IDC were included in the study, and clinicopathological characteristics were compared. Results We included 39 cases of SPC in our study diagnosed during the study period. During the same timeline, 634 cases of IDC were reported and therefore included in the study for comparison. The mean age of the patients with SPC was 53.97 ± 12.15 years, and the mean tumour size was 3.42 ± 1.87 cm. Axillary metastasis was noted in 15.4% of cases. 94.9% of cases of SPC were invasive. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2/neu) and synaptophysin positivity was seen in 84.6%, 87.2%, 10.3%, and 59% respectively. Recurrence was noted in 10.3% of cases with 94.9% survival rate. Cases of SPC had significantly lower grade (grade I + II), tumour (T) and nodal (N) stage than IDC. Moreover, the frequency of hormonal receptor expression (ER and PR) was higher, and the frequency of human epidermal growth factor receptor 2 (HER2/neu) expression was lower compared to IDC. Conclusion SPC is a distinct variant of malignant papillary breast tumours with overall better prognostic parameters than IDC. Therefore, it is essential to recognize the histological features of this rare breast tumour.}, } @article {pmid33262647, year = {2020}, author = {Kunnuru, SKR and Thiyagarajan, M and Martin Daniel, J and Singh K, B}, title = {A Study on Clinical and Pathological Responses to Neoadjuvant Chemotherapy in Breast Carcinoma.}, journal = {Breast cancer (Dove Medical Press)}, volume = {12}, number = {}, pages = {259-266}, pmid = {33262647}, issn = {1179-1314}, abstract = {AIM AND OBJECTIVES: To assess the effectiveness of neo-adjuvant chemotherapy and its impact on the clinical and pathological response in locally advanced breast cancer. To compare molecular subtypes of breast cancer with response to neo-adjuvant chemotherapy.

PATIENTS AND METHODS: This was a prospective study on patients who received neoadjuvant chemotherapy for breast carcinoma for a 3-year period. A total of 60 patients who presented with locally advanced breast cancer (LABC) were treated with neoadjuvant chemotherapy. Forty patients were treated with the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) schedule, 16 patients were treated with Adriamycin and cyclophosphamide (AC), and four patients were treated with oral cyclophosphamide, intravenous methotrexate, and fluorouracil (CMF). Taxol was added in all node-positive cases, triple negative breast cancer (TNBC), and Her 2 positive cases. The clinical response was assessed with RECIST criteria after neoadjuvant chemotherapy. The response was compared with molecular subtypes of carcinoma breast and receptor status individually.

RESULTS: A total of 60 female patients receiving primary chemotherapy for locally advanced breast malignancy were studied. The median age of the patients at the time of diagnosis was 44 years (range=24-73). In terms of menopausal status, 25 (42%) patients were pre-menopausal and 35 (58%) patients were post-menopausal. Histological classification showed invasive ductal carcinoma in 72% of patients, invasive lobular carcinoma in 15% of patients, and other types including mixed patterns in 13% of patients. Among 60 patients, 16 patients (26.6%) had clinically complete remission (cCR), 30 patients (50%) had partial remission, eight patients (13.3%) had stable disease, and six patients (10%) had progressive disease. Following neoadjuvant chemotherapy, 46 (76.6%) patient underwent Modified radical mastectomy surgery. Target therapy was given for Her2 neu patients after surgery. Hormonal therapy was added to hormone ER PR positive cases postoperatively. Eight patients (13.3%) among this operated cases attained complete pathological response.

CONCLUSION: Preoperative chemotherapy downstages the primary tumors and axillary metastasis in patients with locally advanced breast carcinoma. Comparison of molecular subtypes with chemotherapy response is a better way to find out the predictors of response to chemotherapy.}, } @article {pmid33257728, year = {2020}, author = {de Vera, P and Azzolini, M and Sushko, G and Abril, I and Garcia-Molina, R and Dapor, M and Solov'yov, IA and Solov'yov, AV}, title = {Multiscale simulation of the focused electron beam induced deposition process.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20827}, pmid = {33257728}, issn = {2045-2322}, support = {1197139//Alexander von Humboldt-Stiftung/ ; FJCI-2017-32233//Ministerio de Ciencia e Innovación/ ; PGC2018-096788-B-I00//Ministerio de Ciencia e Innovación/ ; 19907/GERM/15//Fundación Séneca/ ; AICO/2019/070//Conselleria d'Educació, Investigació, Cultura i Esport/ ; CA17126//European Cooperation in Science and Technology/ ; 415716638//Deutsche Forschungsgemeinschaft/ ; GRK1885//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Focused electron beam induced deposition (FEBID) is a powerful technique for 3D-printing of complex nanodevices. However, for resolutions below 10 nm, it struggles to control size, morphology and composition of the structures, due to a lack of molecular-level understanding of the underlying irradiation-driven chemistry (IDC). Computational modeling is a tool to comprehend and further optimize FEBID-related technologies. Here we utilize a novel multiscale methodology which couples Monte Carlo simulations for radiation transport with irradiation-driven molecular dynamics for simulating IDC with atomistic resolution. Through an in depth analysis of [Formula: see text] deposition on [Formula: see text] and its subsequent irradiation with electrons, we provide a comprehensive description of the FEBID process and its intrinsic operation. Our analysis reveals that simulations deliver unprecedented results in modeling the FEBID process, demonstrating an excellent agreement with available experimental data of the simulated nanomaterial composition, microstructure and growth rate as a function of the primary beam parameters. The generality of the methodology provides a powerful tool to study versatile problems where IDC and multiscale phenomena play an essential role.}, } @article {pmid33257364, year = {2020}, author = {Ramakrishna, KN and Durland, J and Ramos, C and Dhamoon, AS}, title = {Unilateral nipple discharge in a man without a palpable mass diagnosed as breast cancer.}, journal = {BMJ case reports}, volume = {13}, number = {11}, pages = {}, pmid = {33257364}, issn = {1757-790X}, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms, Male/*diagnosis/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/therapy ; Carcinoma, Papillary/*diagnosis/therapy ; Combined Modality Therapy ; Humans ; Male ; Mastectomy ; Neoplasms, Multiple Primary/diagnosis/therapy ; *Nipple Discharge ; Tamoxifen/therapeutic use ; }, abstract = {A 69-year-old man without a family history of breast cancer presented to his primary care physician with a 1-year history of clear, unilateral nipple discharge (ND) without an associated palpable breast mass. His laboratory findings were significant for hyperprolactinaemia at 28 ng/mL. Diagnostic work up including mammography, ultrasound and core needle biopsy ultimately revealed a ductal carcinoma in situ and a rare papillary variant of invasive ductal carcinoma. The patient was referred to a multidisciplinary oncology team and underwent a right total mastectomy followed by adjuvant hormonal therapy. The patient made a good postoperative recovery and remains without evidence of recurrence 6 months from surgery. Male breast cancer is rare, but its incidence is increasing. Male breast cancer presenting as ND without a palpable mass is uncommon. Early recognition of breast symptoms in men can lead to earlier diagnoses and improved outcomes.}, } @article {pmid33251496, year = {2020}, author = {Li, X and Schmöhl, F and Qi, H and Bennewitz, K and Tabler, CT and Poschet, G and Hell, R and Volk, N and Poth, T and Hausser, I and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J}, title = {Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish.}, journal = {iScience}, volume = {23}, number = {12}, pages = {101763}, pmid = {33251496}, issn = {2589-0042}, abstract = {Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b [-/-] mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b [-/-] embryos. Akr1a1b [-/-] mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b [-/-] mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis.}, } @article {pmid33250747, year = {2020}, author = {Semba, R and Horimoto, Y and Arakawa, A and Edahiro, Y and Takaku, T and Iijima, K and Saito, M}, title = {Difficulty Diagnosing a Brain Tumor during Clinical Maintenance of a Complete Response to anti-HER2 Treatments for Metastatic Breast Cancer: A Case Report.}, journal = {Case reports in oncology}, volume = {13}, number = {3}, pages = {1311-1316}, pmid = {33250747}, issn = {1662-6575}, abstract = {A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.}, } @article {pmid33250296, year = {2021}, author = {Shin, K and Whitman, GJ}, title = {Clinical Indications for Mammography in Men and Correlation With Breast Cancer.}, journal = {Current problems in diagnostic radiology}, volume = {50}, number = {6}, pages = {792-798}, doi = {10.1067/j.cpradiol.2020.11.001}, pmid = {33250296}, issn = {1535-6302}, mesh = {Breast ; *Breast Diseases ; *Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Male ; Mammography ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: The purpose of this study is to examine the correlation between presenting clinical symptoms and imaging findings in men with breast cancer.

METHOD AND MATERIALS: Four hundred twenty-nine male patients who presented for mammography at one institution between January 2004 and December 2014 were retrospectively evaluated. Of the 429 patients, 291 presented with clinical symptoms for diagnostic mammography. The presenting clinical symptoms in 291 patients were recorded and correlated with imaging and histopathologic findings.

RESULTS: Two hundred ninety-one male patients were included. Some presented with multiple symptoms, for a total of 318 clinical symptoms. One hundred and ninety (65%) men presented with palpable abnormalities, 44 (15%) with nonfocal pain, 31 (11%) with breast swelling, 14 (5%) with breast enlargement, 13 (4%) with focal pain, 7 (2%) with skin changes, 6 (2%) with nipple discharge/changes and 13 (4%) with other symptoms (itching, throbbing and breast heaviness). A total of 290 patients underwent mammography and 176 underwent sonography. Forty-one malignancies were diagnosed, of which 24 (59%) were invasive ductal carcinoma. Nipple changes/discharge had a 100% positive predictive value for malignancy while breast pain showed a 0% positive predictive value. Fifty-two patients showed either a mass or a focal asymmetry on mammography, of which 38 (73%) were malignant. Three patients (1%) without a mass or focal asymmetry were diagnosed with malignancy.

CONCLUSION: Correlating clinical symptoms and imaging findings can help with timely and accurate diagnosis of breast cancer in men. Nipple discharge/changes and skin changes with palpable abnormalities and mammographic findings of masses and focal asymmetries were associated with breast cancer. Pain, breast enlargement, and breast swelling were unlikely to be associated with malignancy.}, } @article {pmid33248010, year = {2021}, author = {Ramakrishna, JM and Brumble, LM and Larimore, KL and Wadei, HM and Jarmi, T and Libertin, CR}, title = {Establishing best practices in measles, mumps, and rubella serologic screening for kidney transplant candidates.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {23}, number = {3}, pages = {e13529}, doi = {10.1111/tid.13529}, pmid = {33248010}, issn = {1399-3062}, support = {PFI-260399/FP00105263/17-004563//Pfizer Foundation/ ; }, mesh = {Antibodies, Viral ; Florida ; Humans ; *Kidney Transplantation ; *Measles ; Measles-Mumps-Rubella Vaccine ; *Mumps ; Retrospective Studies ; *Rubella ; Vaccination ; }, abstract = {Optimizing immunity against vaccine-preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al, World J Transplant, 2019, 9:1; Sester et al, Transplant Rev, 2008, 22:274; Fishman, N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live-attenuated vaccines are contraindicated post-transplantation (Malinis et al, Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan-Do-Study-Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol-driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre-KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre-KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%-87.4% post-PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol-driven orders combined with our pre-existing IDCs.}, } @article {pmid33247280, year = {2020}, author = {Puzis, R and Farbiash, D and Brodt, O and Elovici, Y and Greenbaum, D}, title = {Increased cyber-biosecurity for DNA synthesis.}, journal = {Nature biotechnology}, volume = {38}, number = {12}, pages = {1379-1381}, pmid = {33247280}, issn = {1546-1696}, mesh = {*Computer Security ; DNA/*biosynthesis ; Genetic Engineering ; Plasmids/genetics ; }, } @article {pmid33245711, year = {2020}, author = {Sigei, AC and Bartow, BB and Wheeler, Y}, title = {Sentinel Lymph Node Involvement by Epithelial Inclusions Mimicking Metastatic Carcinoma: A Diagnostic Pitfall.}, journal = {The American journal of case reports}, volume = {21}, number = {}, pages = {e926094}, pmid = {33245711}, issn = {1941-5923}, mesh = {Axilla ; *Breast Neoplasms/diagnosis/surgery ; *Carcinoma ; Frozen Sections ; Humans ; Lymph Nodes ; *Sentinel Lymph Node ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND An epithelial inclusion cyst within a lymph node denotes a heterotopic phenomenon. Nodal epithelial inclusion cysts have been reported in a variety of anatomical locations including pelvic, abdominal, mediastinal, and axillary regions. While nodal melanocytic nevus (also known as nevus cell aggregates) is the most common heterotopic phenomena involving the axillary lymph nodes, the presence of benign epithelial inclusion cysts in axillary lymph nodes is a rare but well-reported finding. Such documentation is in part due to assessment of sentinel lymph nodes in breast cancer becoming standard of care. These epithelial inclusion cysts offer a diagnostic pitfall in evaluation of sentinel lymph node in the setting of breast carcinoma. They also complicate assessment of sentinel lymph node during intraoperative frozen sections analysis. CASE REPORT We report a case of co-existent of benign squamous-type and glandular-type epithelial inclusions cysts in 2 sentinel lymph nodes in a patient with grade III invasive ductal carcinoma involving the left breast. There have been at least 4 cases reported in literature in which benign epithelial inclusion cysts in sentinel lymph nodes were first mistakenly diagnosed as metastatic carcinoma both during intraoperative frozen section analysis and during review of permanent sections. The missed diagnosis could potentially occur intraoperatively during frozen section sentinel lymph node analysis secondarily due to lack of availability of the primary tumor for comparison and inability to use immunohistochemical stains. CONCLUSIONS Pathologists should be aware of this pitfall especially in frozen section analysis of sentinel lymph node to avoid misdiagnosis and its associated potential grave consequences.}, } @article {pmid33243732, year = {2020}, author = {Xu, X and Wang, J and Yan, C and Men, Y and Jiang, H and Fang, H and Xu, X and Yang, J}, title = {[Association of JMJD3, MMP-2 and VEGF expressions with clinicopathological features of invasive ductal breast carcinoma].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {40}, number = {11}, pages = {1593-1600}, pmid = {33243732}, issn = {1673-4254}, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A ; }, abstract = {OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells.

METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR.

RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue (P < 0.05). The positivity rates of JMJD3, MMP-2 and VEGF in breast cancer tissues were significantly correlated with tumor diameter, differentiation, TNM stage, lymph node metastasis, and molecular subtypes (P < 0.05). KaplanMeier analysis showed that JMJD3 expression level was positively while MMP-2 and VEGF were inversely correlated with the disease-free survival time of the patients (P < 0.05). Cox regression analysis identified JMJD3, MMP-2, VEGF and tumor differentiation as independent prognostic factors of breast cancer. Spearman correlation analysis suggested a negative correlation of JMJD3 with MMP2 (r=-0.569, P < 0.05) and VEGF (r=-0.533, P < 0.05) and a positive correlation between MMP2 and VEGF (r=0.923, P < 0.05). In MDA-MB-231 cells, overexpression of JMJD3 inhibited the proliferation of MDA-MB-231 cells and the expression of MMP-2 and VEGF.

CONCLUSIONS: The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.}, } @article {pmid33240433, year = {2021}, author = {Xu, S and Chen, T and Dong, L and Li, T and Xue, H and Gao, B and Ding, X and Wang, H and Li, H}, title = {Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism.}, journal = {Oncology letters}, volume = {21}, number = {1}, pages = {27}, pmid = {33240433}, issn = {1792-1074}, abstract = {Fatty acid metabolism is closely associated with the occurrence and development of tumors. The aim of the present study was to investigate whether the key enzyme involved in fatty acid synthesis, fatty acid synthase (FASN), mediates fatty acid changes that affect the activity and migration of breast cancer cells, and whether specific fatty acids play a role in tumor metastasis. The difference in serum fatty acid profiles between patients with invasive ductal carcinoma (IDC) and healthy controls was evaluated by gas chromatography-mass spectrometry (GC-MS) fatty acid profile analysis, and it was revealed that five types of fatty acids may be potential tumor markers in IDC. Immunohistochemistry and GC-MS analysis revealed that FASN expression affected the serum fatty acid profiles of patients with IDC. Following FASN knockdown, the migration of SK-Br-3 breast cancer cells was inhibited, and the contents of various fatty acids both inside and outside the cell decreased, while the contents of various fatty acids inside and outside the cell increased following FASN overexpression. The results of the present study revealed that the expression level of FASN affected the content of fatty acids in IDC tissues and breast cancer cell lines, and that FASN-mediated changes in specific fatty acids promoted tumor cell migration.}, } @article {pmid33239449, year = {2021}, author = {Chen, J and Fleming, T and Katz, S and Dewenter, M and Hofmann, K and Saadatmand, A and Kronlage, M and Werner, MP and Pokrandt, B and Schreiter, F and Lin, J and Katz, D and Morgenstern, J and Elwakiel, A and Sinn, P and Gröne, HJ and Hammes, HP and Nawroth, PP and Isermann, B and Sticht, C and Brügger, B and Katus, HA and Hagenmueller, M and Backs, J}, title = {CaM Kinase II-δ Is Required for Diabetic Hyperglycemia and Retinopathy but Not Nephropathy.}, journal = {Diabetes}, volume = {70}, number = {2}, pages = {616-626}, doi = {10.2337/db19-0659}, pmid = {33239449}, issn = {1939-327X}, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/*metabolism ; Diabetic Nephropathies/genetics/*metabolism ; Diabetic Retinopathy/genetics/*metabolism ; Gene Expression ; Hyperglycemia/genetics/*metabolism ; Mice ; Mice, Knockout ; Receptors, Leptin/genetics/metabolism ; }, abstract = {Type 2 diabetes has become a pandemic and leads to late diabetic complications of organs, including kidney and eye. Lowering hyperglycemia is the typical therapeutic goal in clinical medicine. However, hyperglycemia may only be a symptom of diabetes but not the sole cause of late diabetic complications; instead, other diabetes-related alterations could be causative. Here, we studied the role of CaM kinase II-δ (CaMKIIδ), which is known to be activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we provide evidence for improved insulin sensing with increased glucose transport into skeletal muscle and also reduced hepatic glucose production. Despite normoglycemia, CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy, but diabetic retinopathy was prevented. We also unmasked a retina-specific gene expression signature that might contribute to CaMKII-dependent retinal diabetic complications. These data challenge the clinical concept of normalizing hyperglycemia in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolic signals in different diabetic organs.}, } @article {pmid33238981, year = {2020}, author = {Huang, Z and Hu, C and Liu, K and Yuan, L and Li, Y and Zhao, C and Hu, C}, title = {Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infiltrating duct carcinoma of the breast: a population-based study.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {1145}, pmid = {33238981}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*secondary/therapy ; Brain Neoplasms/*secondary/therapy ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*secondary/therapy ; Male ; Middle Aged ; *Nomograms ; Prognosis ; Retrospective Studies ; Risk Factors ; SEER Program ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women, and it is also the leading cause of death in female patients; the most common pathological type of BC is infiltrating duct carcinoma (IDC). Some nomograms have been developed to predict bone metastasis (BM) in patients with breast cancer. However, there are no studies on diagnostic and prognostic nomograms for BM in newly diagnosed IDC patients.

METHODS: IDC patients with newly diagnosed BM from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were reviewed. Multivariate logistic regression analysis was used to identify risk factors for BM in patients with IDC. Univariate and multivariate Cox proportional hazards regression analysis were used to explore the prognostic factors of BM in patients with IDC. We then constructed nomograms to predict the risk and prognosis of BM for patients with IDC. The results were validated using bootstrap resampling and retrospective research on 113 IDC patients with BM from 2015 to 2018 at the Affiliated Hospital of Chengde Medical University.

RESULTS: This study included 141,959 patients diagnosed with IDC in the SEER database, of whom 2383 cases were IDC patients with BM. The risk factors for BM in patients with IDC included sex, primary site, grade, T stage, N stage, liver metastasis, race, brain metastasis, breast cancer subtype, lung metastasis, insurance status, and marital status. The independent prognostic factors were brain metastases, race, grade, surgery, chemotherapy, age, liver metastases, breast cancer subtype, insurance status, and marital status. Through calibration, receiver operating characteristic curve and decision curve analyses, we found that the nomogram for predicting the prognosis of IDC patients with BM displayed great performance both internally and externally.

CONCLUSION: These nomograms are expected to be a precise and personalized tool for predicting the risk and prognosis for BM in patients with IDC. This will help clinicians develop more rational and effective treatment strategies.}, } @article {pmid33238073, year = {2021}, author = {Okada, K and Takahara, T and Suzuki, Y and Kohno, K and Sakakibara, A and Satou, A and Takahashi, E and Nakamura, S}, title = {Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.}, journal = {Pathology international}, volume = {71}, number = {1}, pages = {24-32}, doi = {10.1111/pin.13044}, pmid = {33238073}, issn = {1440-1827}, mesh = {Adolescent ; Adult ; Aged ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/analysis ; *Dendritic Cell Sarcoma, Follicular/immunology/metabolism/pathology ; Dendritic Cells/metabolism/pathology ; Female ; Histiocytes/metabolism/pathology ; *Histiocytic Sarcoma/immunology/metabolism/pathology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Japan ; Langerhans Cell Sarcoma/immunology/metabolism/pathology ; Lymphoma, Follicular/immunology/metabolism/pathology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes/metabolism ; }, abstract = {Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.}, } @article {pmid33237591, year = {2021}, author = {Graetz, DE and Chen, Y and Devidas, M and Antillon-Klussmann, F and Fu, L and Quintero, K and Fuentes-Alabi, SL and Gassant, PY and Kaye, EC and Baker, JN and Rodriguez Galindo, C and Mack, JW}, title = {Interdisciplinary care of pediatric oncology patients in Central America and the Caribbean.}, journal = {Cancer}, volume = {127}, number = {14}, pages = {2579-2586}, doi = {10.1002/cncr.33339}, pmid = {33237591}, issn = {1097-0142}, support = {//American Lebanese Syrian Associated Charities/ ; }, mesh = {Child ; Cross-Sectional Studies ; Humans ; Interdisciplinary Communication ; Medical Oncology ; *Neoplasms/therapy ; *Oncologists ; Patient Care Team ; }, abstract = {BACKGROUND: Interdisciplinary teamwork supports high-quality cancer care and effective utilization of limited resources. This study purposed to examine the value, structure, process, and effectiveness of interdisciplinary care (IDC) among pediatric oncology providers in low-income and middle-income countries in Central America and the Caribbean.

METHODS: A cross-sectional survey was disseminated to pediatric oncology providers at 5 centers participating in the Pediatric Hematology-Oncology Association of Central America. The survey included previously validated items and novel questions assessing the value (importance), structure (multidisciplinary meeting attendance), process (team climate), and effectiveness (job satisfaction, quality of care and communication) of IDC.

RESULTS: The survey was completed by 174 providers, including 22 oncologists, 9 pathologists, 9 radiologists, 5 radiation oncologists, 12 surgeons, 35 subspecialists, 60 nurses, 20 psychosocial providers, and 2 other staff. Participants agreed that IDC benefits team members (95%) and patients (96%). IDC structure and processes varied across the region. Multidisciplinary meeting attendance differed by center (P = .005) and discipline (P < .0001). Participants who frequently attended multidisciplinary meetings reported a more positive team climate (P = .0003). Team climate was positively associated with job satisfaction (P < .001). In multivariable analyses, team climate was predictive of an improved perception of communication between professionals (P < .0001), with families (P < .0001), and with patients (P = .0005), as well as with quality of the care environment (P = .006) and overall care quality (P < .0001).

CONCLUSIONS: Nearly all surveyed participants valued IDC, and the structure and processes supporting IDC varied by center. Associations between a collaborative professional climate, job satisfaction, and the perception of quality care encourage continued investigation and prioritization of IDC in these settings.}, } @article {pmid33235571, year = {2020}, author = {Djordjevic, M and Karanikolic, A and Velickovic, L and Milentijevic, M}, title = {Association of axillary node status with clinicopathological characteristics and expression of EZH2 and CD44 in primary breast ductal carcinoma.}, journal = {Pakistan journal of medical sciences}, volume = {36}, number = {7}, pages = {1539-1544}, pmid = {33235571}, issn = {1682-024X}, abstract = {OBJECTIVE: In order to enhance the prognostic benefit of new molecular markers, the aim of this study was to identify possible association of axillary lymph node (ALN) status and pN with clinicopathological characteristics and expression of EZH2 and CD44 in invasive ductal carcinoma (IDC) of the breast.

METHODS: The investigation included 106 patients with IDC who had undergone radical mastectomy at the Clinic of Endocrine Surgery in Nis. Clinicopathologic parameters and immunohistochemical expression of EZH2 and CD44 in primary IDC were investigated in relation to ALN status and pN.

RESULTS: Our univariate analysis established that T3-T4 stage, high EZH2, and high EZH2 with ER- were associated with ALN metastasis (p=0.014; 0.003; 0.013). Decreased probability for ALN involvement was found with T1 stage, and low EZH2 with ER+ (p=0.032; 0.022). Multivariant analysis established that high EZH2 in cancer cells was associated with high risk for ALN metastases (p=0.004); T1 tumors were associated with low risk (p=0.037). Higher pN was associated with high EZH2, high EZH2 with ER-, as well as an advanced clinical and disease stage (p=0.006; 0.001; p=0.002, 0.001). Lower pN was associated with ER+, and ER+ with low EZH2 (p= 0.004; 0.012). CD44 was not associated with ALN involvement, nor with pN.

CONCLUSIONS: This study revealed association of EZH2 with ALN metastases, where disease stage and expression profiles of EZH2 and ER may have affected regional pN.}, } @article {pmid33231786, year = {2022}, author = {Rachamim, L and Zimmerman-Brenner, S and Rachamim, O and Mualem, H and Zingboim, N and Rotstein, M}, title = {Internet-based guided self-help comprehensive behavioral intervention for tics (ICBIT) for youth with tic disorders: a feasibility and effectiveness study with 6 month-follow-up.}, journal = {European child & adolescent psychiatry}, volume = {31}, number = {2}, pages = {275-287}, pmid = {33231786}, issn = {1435-165X}, mesh = {Adolescent ; *COVID-19 ; Child ; Feasibility Studies ; Follow-Up Studies ; Humans ; Internet ; Pandemics ; Psychotherapy ; SARS-CoV-2 ; *Telemedicine ; *Tic Disorders/therapy ; *Tics ; Treatment Outcome ; }, abstract = {Practice guidelines endorse comprehensive behavioral intervention for tics (CBIT) as first-line treatment for tic disorders (TD) in youth. Nevertheless, CBIT is rarely available due to various barriers. This study evaluated the feasibility and potential effectiveness of an Internet-based, self-help CBIT program (ICBIT) guided by parents with minimal therapist support delivered via telepsychotherapy. Forty-one youths, aged 7-18 years, were randomly assigned to receive either ICBIT (n = 25) or a wait-list (WL) condition (n = 16) in a crossover design. ICBIT was feasible to implement and at post-treatment, 64% of the participants have improved significantly. Results demonstrated clinically meaningful reductions in tic severity and improved youth global impairment and functioning. Gains were maintained over a 6-month follow-up period. The effect size for the primary outcome measure (Yale Global Tic Severity Scale) ranged between large effect size (Cohen"s d = 0.91) at post-intervention to very large effect size (Cohen's d = 2.25) 6 months after the end of the acute intervention. These were comparable to face-to-face delivery treatment trials for TD. Participants rated the intervention as highly acceptable and satisfactory. Youth receiving ICBIT experienced improvement in self-esteem and comorbidity. Finally, during the COVID-19 pandemic, the ICBIT program enabled the delivery of the intervention consecutively without interruption. The results observed provide preliminary evidence of the feasibility and effectiveness of this innovative modality to assist youth with TD and remove various barriers to treatment, including those during a public crisis, such as the COVID-19 pandemic. Larger studies with an active control group are warranted.Trial registration URL: http://clinicaltrials.gov, ClinicalTrials.gov Identifier: NCT04087616.}, } @article {pmid33229203, year = {2021}, author = {Madabhavi, I and Sarkar, M and Chavan, C and Trivedi, M}, title = {Maxillary bone metastasis, as an early sign of breast cancer; an unusual & rare site of metastasis from the common cancer.}, journal = {Oral oncology}, volume = {115}, number = {}, pages = {105098}, doi = {10.1016/j.oraloncology.2020.105098}, pmid = {33229203}, issn = {1879-0593}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Maxilla/*pathology ; Maxillary Neoplasms/*secondary ; Neoplasm Metastasis ; }, abstract = {Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Due to their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. In this article we present a rare, unusual & exceptional case of left maxillary mass which on further evaluation leading to diagnosis of left breast carcinoma with metastasis to isolated left maxillary bone. Sixty five year old postmenopausal woman of low socioeconomic status with good performance status presented with a 3 months history of progressive pain and swelling in the left maxillary region. Fine Needle Aspiration Cytology (FNAC) from the maxillary mass shows invasive ductal carcinoma. On further clinical, radiographic, and histopathological examination findings from the breast lesion confirmed the diagnosis of hormone receptor positive metastatic breast carcinoma. In view of painful metastatic maxillary lesion with breast disease she was managed with a palliative radiotherapy to the maxillary lesion and palliative chemotherapy with Doxorubicin-Cyclophosphamide and bhisphosphonate-Zolendronic acid. Patient responded very well to palliative radiotherapy and chemotherapy, in view of hormone receptor positive breast cancer, now she is on Tab. Anastrazole 1 mg once a day along with monthly Zolendronic acid injection since last 13 months without any symptoms of disease evolution. A high index of clinical thought of metastatic cancer to maxilla is necessary when evaluating patients who complain of maxillary pain and swelling without a history of pain or swelling in the head and neck & non-head and neck region. To the best of our knowledge, this is the first reported case of a metastatic isolated solitary maxillary bone metastasis presenting as an early sign of breast cancer.}, } @article {pmid33228656, year = {2020}, author = {Adani-Ifè, A and Amégbor, K and Doh, K and Darré, T}, title = {Breast cancer in togolese women: immunohistochemistry subtypes.}, journal = {BMC women's health}, volume = {20}, number = {1}, pages = {261}, pmid = {33228656}, issn = {1472-6874}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Togo ; }, abstract = {BACKGROUND: Molecular classification of breast cancer is an important factor for prognostic and clinical outcomes. There are no data regarding molecular breast cancer subtypes among Togolese women. The objective of this study was to evaluate the expression of ER, PR, HER2, and molecular subtypes of breast cancer receptors in Togolese patients and to establish the correlation between clinical and histological data and molecular types.

METHODS: Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR, and HER2) were assessed in patients who have been diagnosed with invasive breast cancer from March 2016 to March 2020 in the department of oncology. The analysis of variance and the Chi-square Test was used to analyze the data.

RESULTS: A total of 117 cases were collected. The mean age of patients was 52.05 ± 12.38 with an age range of 30 to 85 years. Half of the patients were over 50 years old and the majority (70.9%) was postmenopausal. More than half of patients (52.1%) presented with T3-T4tumors.The most common histologic subtype of breast cancer was invasive ductal carcinoma of no special type (95.7%). Tumors grade 2 were predominant (51.3%) followed by grade 3 (42.7%). Advanced carcinomas were found in 69 patients (59%). The percentage of ER+, PR+, and HER2 positive tumors was 54.7%, 41%, and 15.4% respectively. The predominant molecular subtype was Triple negative (37.6%), followed by Luminal A (30.8.7%), Luminal B subtype (23.9%), and HER2 enriched (7.7%). There was a significant association between stage and breast cancer subtypes (p 0.025), histologic grade, and subtype (p < 0.0001) but no correlation was found with age, menopausal status, and tumor size.

CONCLUSION: Breast carcinoma in our patients are high grade tumors and are diagnosed at an advanced stage. Triple negative and Luminal A are the two predominant breast cancer subtypes in Togolese women. Consequently, Receptor testing availability should be a priority to offer the best breast cancer treatment.}, } @article {pmid33214271, year = {2020}, author = {Greenbaum, D}, title = {Space debris puts exploration at risk.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6519}, pages = {922}, doi = {10.1126/science.abf2682}, pmid = {33214271}, issn = {1095-9203}, } @article {pmid33209515, year = {2020}, author = {Sabir, AU and Sabir, S and Abbas, S}, title = {Bloody Aggressive: A Case Report on a Fungating Breast Mass in a Paraplegic Requiring Emergency Mastectomy.}, journal = {Cureus}, volume = {12}, number = {10}, pages = {e10952}, pmid = {33209515}, issn = {2168-8184}, abstract = {Fungating malignant lesions pose a huge deal of agony to the patients. Their management is also deemed as difficult by most physicians. This report describes a case of a 45-year-old paraplegic female with delayed presentation of a very aggressive fungating left breast mass, which was diagnosed as invasive ductal carcinoma. The uncontrollable hemorrhage had the surgeons succumb to the option of emergency mastectomy as a palliative treatment to save the life of the patient. Hence, we infer that the emergency mastectomy in a hemorrhagic fungating breast lesion can be life-saving and can be performed with little to no risk to the patient. Such a procedure, surprisingly, has never been documented in the surgical literature before.}, } @article {pmid33209168, year = {2020}, author = {Fouhi, ME and Benider, A and Gaëtan, KZA and Mesfioui, A}, title = {[Epidemiological and anatomopathological profile of breast cancer at the Ibn Rochd University Hospital, Casablanca].}, journal = {The Pan African medical journal}, volume = {37}, number = {}, pages = {41}, pmid = {33209168}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Delayed Diagnosis ; Female ; Hospitals, University ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {The present study aims to determine the various epidemiological characteristics among newly diagnosed patients with breast cancer in Casablanca during 2018. During that period, 668 cases were collected, the average age was 51.6 years, the female was the most represented with 662 cases (99.1%) and men with 6 cases (0.9%), a sex ratio (M/F) of 0.009. The average age of menopause was 49.8 years and the average age of menarche was 13.5 years, 31.7% had a history of cancer (breast 14.1%, stomach and 9% liver 7%). The average diagnosis delay was 10 months, the thyroid disease was the most represented pathology, the left breast was diagnosed in 50.2% and the right breast in 44.7% and 1.3% in the bilateral location. The most common histological type was invasive ductal carcinoma (73.2%). The vascular and lymphatic invasion was observed in 42.2%, axillary nodes were affected in 71.1% of cases. The histological prognosis (SBR) revealed a predominance of grade II in 55.9% of cases. The Luminal B continues to be the most common phenotype (46%) followed by Triple Negative (15.3%) and Luminal A (14.2%) and HER2 (7.4%). The immediate prognosis is a cause for concern because of delayed diagnosis. It seems urgent to develop the health information policy and education.}, } @article {pmid33209111, year = {2020}, author = {Hassan, MA and Fakhrudiin, N and Farhat, F}, title = {Synchronous invasive ductal carcinoma of the breast and clear cell renal carcinoma with rare presentation and behaviour: a case report with a literature review.}, journal = {Ecancermedicalscience}, volume = {14}, number = {}, pages = {1120}, pmid = {33209111}, issn = {1754-6605}, abstract = {The presence of two or more primary tumours is a relatively uncommon phenomenon. Recently with the improvement of diagnostic modalities, such cases are increasingly reported in the literature. This paper presents a rare case of synchronous breast and renal tumour with unusual features including RCC metastasis to the duodenum and stomach, rapid recurrence of the tumour at the nephrectomy site, rapid renal cell carcinoma growth rate and the rare presence of syncytial-type giant cells in the renal cell tumour.}, } @article {pmid33204769, year = {2020}, author = {Buus, TW and Sivesgaard, K and Fris, TL and Christiansen, PM and Jensen, AB and Pedersen, EM}, title = {Fat fractions from high-resolution 3D radial Dixon MRI for predicting metastatic axillary lymph nodes in breast cancer patients.}, journal = {European journal of radiology open}, volume = {7}, number = {}, pages = {100284}, pmid = {33204769}, issn = {2352-0477}, abstract = {PURPOSE: To assess diagnostic performance of fat fractions (FF) from high-resolution 3D radial Dixon MRI for differentiating metastatic and non-metastatic axillary lymph nodes in breast cancer patients.

METHOD: High-resolution 3D radial Dixon MRI was prospectively performed on 1.5 T in 70 biopsy-verified breast cancer patients. 35 patients were available for analysis with histopathologic and imaging data. FF images were calculated as fat / in-phase. Two radiologists measured lymph node FF and assessed morphological features in one ipsilateral and one contralateral lymph node in consensus. Diagnostic performance of lymph node FF and morphological criteria were compared using histopathology as reference.

RESULTS: 22 patients had metastatic axillary lymph nodes. Mean lymph node FF were 0.20 ± 0.073, 0.31 ± 0.079, and 0.34 ± 0.15 (metastatic, non-metastatic ipsi- and non-metastatic contralateral lymph nodes, respectively). Metastatic lymph node FF were significantly lower than non-metastatic ipsi- (p <  0.001) and contralateral lymph nodes (p <  0.001). Area under the receiver operating characteristics curve for lymph node FF was 0.80 compared to 0.76 for morphological criteria (p =  0.29). Lymph node FF yielded sensitivity 0.91, specificity 0.69, positive predictive value (PPV) 0.83, and negative predictive value (NPV) 0.82, while morphological criteria yielded sensitivity 0.91, specificity 0.62, PPV 0.80, and NPV 0.80 (p =  0.71). Combining lymph node FF and morphological criteria increased diagnostic performance with sensitivity 1.00, specificity 0.67, PPV 0.86, NPV 1.00, and AUC 0.83.

CONCLUSIONS: Lymph node FF from high-resolution 3D Dixon images are a promising quantitative indicator of metastases in axillary lymph nodes.}, } @article {pmid33204409, year = {2020}, author = {Missori, G and Serra, F and Prestigiacomo, G and Ricciardolo, AA and Brugioni, L and Gelmini, R}, title = {Case Report: Metastatic breast cancer to the gallbladder.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {343}, pmid = {33204409}, issn = {2046-1402}, mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; *Cholecystitis, Acute/etiology/surgery ; Female ; *Gallbladder Neoplasms/secondary/surgery ; Humans ; }, abstract = {Cholecystitis is one of the leading causes of emergency surgical interventions; the occurrence of metastases to the gallbladder is rare and has only been reported in the literature exceptionally. Metastatic breast cancer to the gallbladder is even less frequent; in fact, breast cancer usually metastasizes to bone, lung, lymph nodes, liver and brain. We report the case of an 83-year-old female patient with a previous history of breast surgery with axillary dissection in 1997, followed by adjuvant chemotherapy due to invasive ductal carcinoma of the left breast. The patient was admitted at the emergency department for sepsis and an episode of acute kidney failure, anuria and fever. Right-upper quadrant abdominal pain triggered by food intake and abdominal tenderness was also present, placing the diagnostic suspicion of biliary sepsis due to acute cholecystitis. The histological examination of the surgical specimen highlighted the presence of metastasis from an infiltrating ductal breast carcinoma with positive hormone receptors. We also report here the results of a review of the literature looking at articles describing cases of gallbladder metastasis from breast cancer.}, } @article {pmid33200356, year = {2021}, author = {Ueda, D and Yamamoto, A and Takashima, T and Onoda, N and Noda, S and Kashiwagi, S and Morisaki, T and Tsutsumi, S and Honjo, T and Shimazaki, A and Goto, T and Miki, Y}, title = {Visualizing "featureless" regions on mammograms classified as invasive ductal carcinomas by a deep learning algorithm: the promise of AI support in radiology.}, journal = {Japanese journal of radiology}, volume = {39}, number = {4}, pages = {333-340}, pmid = {33200356}, issn = {1867-108X}, support = {JP18K15597//Kaken/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/classification/*diagnostic imaging/pathology ; *Deep Learning ; Female ; Humans ; Mammography/*methods ; Middle Aged ; }, abstract = {PURPOSE: To demonstrate how artificial intelligence (AI) can expand radiologists' capacity, we visualized the features of invasive ductal carcinomas (IDCs) that our algorithm, developed and validated for basic pathological classification on mammograms, had focused on.

MATERIALS AND METHODS: IDC datasets were built using mammograms from patients diagnosed with IDCs from January 2006 to December 2017. The developing dataset was used to train and validate a VGG-16 deep learning (DL) network. The true positives (TPs) and accuracy of the algorithm were externally evaluated using the test dataset. A visualization technique was applied to the algorithm to determine which malignant findings on mammograms were revealed.

RESULTS: The datasets were split into a developing dataset (988 images) and a test dataset (131 images). The proposed algorithm diagnosed 62 TPs with an accuracy of 0.61-0.70. The visualization of features on the mammograms revealed that the tubule forming, solid, and scirrhous types of IDCs exhibited visible features on the surroundings, corners of the masses, and architectural distortions, respectively.

CONCLUSION: We successfully showed that features isolated by a DL-based algorithm trained to classify IDCs were indeed those known to be associated with each pathology. Thus, using AI can expand the capacity of radiologists through the discovery of previously unknown findings.}, } @article {pmid33197426, year = {2021}, author = {Tuzuner, MB and Ozturk, T and Ilvan, S and Turna, H and Yurdun, T and Yilmaz-Aydogan, H and Ozturk, O}, title = {Local aromatase activity alterations in breast cancer tissues: A potential way of decision support for clinicians.}, journal = {Experimental and molecular pathology}, volume = {118}, number = {}, pages = {104574}, doi = {10.1016/j.yexmp.2020.104574}, pmid = {33197426}, issn = {1096-0945}, mesh = {Aromatase/*metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/enzymology/*pathology/surgery ; Carcinoma, Ductal, Breast/enzymology/*pathology/surgery ; Case-Control Studies ; *Decision Making ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Precision Medicine ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Stromal Cells/enzymology/*pathology ; Tumor Microenvironment ; }, abstract = {BACKGROUND AND AIMS: It is becoming evident that local estrogen exposure is important in postmenopausal breast cancer patients. The microenvironment is established by breast stromal cells based on communication with tumor cells that is essential to cancer development, invasion, and metastasis. Here we investigated aromatase activity levels in both tumor and matched stromal tissues by showing their impact on the manufacturing of local estrogen and tumor progression in cases of invasive ductal carcinoma (IDC).

METHODS: Tumor (T) and tumor-associated stroma (TAS) neighboring tissues were acquired from each postmenopausal patient, diagnosed with IDC, and categorized as luminal A (n = 20). The control group was formed from tumor-free breast tissue samples (N, n = 12). A microsomal-based technique was created to compare breast tissue aromatase activities using liquid chromatography - mass spectrometry.

FINDINGS: We observed that the TAS tissues have the highest aromatase activities (p < 0.05). High progesterone receptor (PR) intensity levels were found to be decreasing the activity level in these tissues significantly (p < 0.05). Tumor tissue specific aromatase activity levels of postmenopausal patients' were tend to be lower compared to healthy premenopausal subjects' (3 fold, p < 0.001). In addition low activity in tumor tissues were associated with low grade and late stage cancers.

CONCLUSIONS: Early detection and personalized therapy is essential for postmenopausal breast cancer patients. Together, our in-house tandem mass spectrometry technique has the potential for further development and standardization for the measurement of aromatase activity and may assist clinicians decide on therapy policies for postmenopausal IDC patients which could be an invaluable asset for precise and specific evaluation.}, } @article {pmid33194733, year = {2020}, author = {Liang, J and Zeng, S and Li, Z and Kong, Y and Meng, T and Zhou, C and Chen, J and Wu, Y and He, N}, title = {Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Quantitative Differentiation of Breast Tumors: A Meta-Analysis.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {585486}, pmid = {33194733}, issn = {2234-943X}, abstract = {Objectives: The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of breast tumors remains debatable among published studies. Therefore, this meta-analysis aimed to pool relevant evidence regarding the diagnostic performance of IVIM-DWI in the differential diagnosis of breast tumors. Methods: Studies on the differential diagnosis of breast lesions using IVIM-DWI were systemically searched in the PubMed, Embase and Web of Science databases in recent 10 years. The standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D[*]), and perfusion fraction (f) were calculated using Review Manager 5.3, and Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as assess publication bias and heterogeneity. Fagan's nomogram was used to predict the posttest probabilities. Results: Sixteen studies comprising 1,355 malignant and 362 benign breast lesions were included. Most of these studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer had significant lower ADC (SMD = -1.38, P < 0.001) and D values (SMD = -1.50, P < 0.001), and higher f value (SMD = 0.89, P = 0.001) than benign lesions, except D[*] value (SMD = -0.30, P = 0.20). Invasive ductal carcinoma showed lower ADC (SMD = 1.34, P = 0.01) and D values (SMD = 1.04, P = 0.001) than ductal carcinoma in situ. D value demonstrated the best diagnostic performance (sensitivity = 86%, specificity = 86%, AUC = 0.91) and highest post-test probability (61, 48, 46, and 34% for D, ADC, f, and D[*] values) in the differential diagnosis of breast tumors, followed by ADC (sensitivity = 76%, specificity = 79%, AUC = 0.85), f (sensitivity = 80%, specificity = 76%, AUC = 0.85) and D[*] values (sensitivity = 84%, specificity = 59%, AUC = 0.71). Conclusion: IVIM-DWI parameters are adequate and superior to the ADC in the differentiation of breast tumors. ADC and D values can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. IVIM-DWI is also superior in identifying lymph node metastasis, histologic grade, and hormone receptors, and HER2 and Ki-67 status.}, } @article {pmid33194685, year = {2020}, author = {Li, Z and Li, X and Peng, C and Dai, W and Huang, H and Li, X and Xie, C and Liang, J}, title = {The Diagnostic Performance of Diffusion Kurtosis Imaging in the Characterization of Breast Tumors: A Meta-Analysis.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {575272}, pmid = {33194685}, issn = {2234-943X}, abstract = {Rationale and Objectives: Diffusion kurtosis imaging (DKI) is a promising imaging technique, but the results regarding the diagnostic performance of DKI in the characterization and classification of breast tumors are inconsistent among published studies. This study aimed to pool all published results to provide more robust evidence of the differential diagnosis between malignant and benign breast tumors using DKI. Methods: Studies on the differential diagnosis of breast tumors using DKI-derived parameters were systemically retrieved from PubMed, Embase, and Web of Science without a time limit. Review Manager 5.3 was used to calculate the standardized mean differences (SMDs) and 95% confidence intervals of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC). Stata 12.0 was used to pool the sensitivity, specificity, and diagnostic odds ratio (DOR) as well as the publication bias and heterogeneity of each parameter. Fagan's nomograms were plotted to predict the post-test probabilities. Results: Thirteen studies including 867 malignant and 460 benign breast lesions were analyzed. Most of the included studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer showed a higher MK (SMD = 1.23, P < 0.001) but a lower MD (SMD = -1.29, P < 0.001) and ADC (SMD = -1.21, P < 0.001) than benign tumors. The MK (SMD = -1.36, P = 0.006) rather than the MD (SMD = 0.29, P = 0.20) or ADC (SMD = 0.26, P = 0.24) can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. The DKI-derived MK (sensitivity = 90%, specificity = 88%, DOR = 66) and MD (sensitivity = 86% and specificity = 88%, DOR = 46) demonstrated superior diagnostic performance and post-test probability (65, 64, and 56% for MK, MD, and ADC) in differentiating malignant from benign breast lesions, with a higher sensitivity and specificity than the DWI-derived ADC (sensitivity = 85% and specificity = 83%, DOR = 29). Conclusion: The DKI-derived MK and MD demonstrate a comparable diagnostic performance in the discrimination of breast tumors based on their microstructures and non-Gaussian characteristics. The MK can further differentiate invasive ductal carcinoma from ductal carcinoma in situ.}, } @article {pmid33194424, year = {2020}, author = {Li, X and Yu, Q and Chen, J and Huang, H and Liu, Z and Wang, C and He, Y and Zhang, X and Li, W and Li, C and Zhao, J and Long, W}, title = {Prognostic model of invasive ductal carcinoma of the breast based on differentially expressed glycolysis-related genes.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e10249}, pmid = {33194424}, issn = {2167-8359}, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer that is characterized by high malignancy and rapid progression. Upregulation of glycolysis is a hallmark of tumor growth, and correlates with the progression of breast cancer. We aimed to establish a model to predict the prognosis of patients with breast IDC based on differentially expressed glycolysis-related genes (DEGRGs).

METHODS: Transcriptome data and clinical data of patients with breast IDC were from The Cancer Genome Atlas (TCGA). Glycolysis-related gene sets and pathways were from the Molecular Signatures Database (MSigDB). DEGRGs were identified by comparison of tumor tissues and adjacent normal tissues. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen for DEGRGs with prognostic value. A risk-scoring model based on DEGRGs related to prognosis was constructed. Receiver operating characteristic (ROC) analysis and calculation of the area under the curve (AUC) were used to evaluate the performance of the model. The model was verified in different clinical subgroups using an external dataset (GSE131769). A nomogram that included clinical indicators and risk scores was established. Gene function enrichment analysis was performed, and a protein-protein interaction network was developed.

RESULTS: We analyzed data from 772 tumors and 88 adjacent normal tissues from the TCGA database and identified 286 glycolysis-related genes from the MSigDB. There were 185 DEGRGs. Univariate Cox regression and LASSO regression indicated that 13 of these genes were related to prognosis. A risk-scoring model based on these 13 DEGRGs allowed classification of patients as high-risk or low-risk according to median score. The duration of overall survival (OS) was longer in the low-risk group (P < 0.001), and the AUC was 0.755 for 3-year OS and 0.726 for 5-year OS. The results were similar when using the GEO data set for external validation (AUC for 3-year OS: 0.731, AUC for 5-year OS: 0.728). Subgroup analysis showed there were significant differences in OS among high-risk and low-risk patients in different subgroups (T1-2, T3-4, N0, N1-3, M0, TNBC, non-TNBC; all P < 0.01). The C-index was 0.824, and the AUC was 0.842 for 3-year OS and 0.808 for 5-year OS from the nomogram. Functional enrichment analysis demonstrated the DEGRGs were mainly involved in regulating biological functions.

CONCLUSIONS: Our prognostic model, based on 13 DEGRGs, had excellent performance in predicting the survival of patients with IDC of the breast. These DEGRGs appear to have important biological functions in the progression of this cancer.}, } @article {pmid33193929, year = {2021}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Primary lymphoma of the breast: A case report and review of the literature.}, journal = {Radiology case reports}, volume = {16}, number = {1}, pages = {55-61}, pmid = {33193929}, issn = {1930-0433}, abstract = {Primary lymphoma of the breast is a rare disease, accounting for about 0.5% of all primary breast tumors. Often found as a solitary indolent mass, it is difficult to distinguish from breast cancer on imaging and is often diagnosed for the first time based on histological findings. Diffuse large B-cell lymphoma is the most common histological subtype. A 48-year-old woman visited our hospital because of a painless mass in the left breast. Breast cancer was suspected based on the imaging findings. A core needle biopsy was performed, and the invasive ductal carcinoma was diagnosed. Partial mastectomy and sentinel lymph node biopsy were performed. The resected specimen was finally diagnosed as diffuse large B-cell lymphoma based on immunohistochemical staining. The patient was treated with R-CHOP and intrathecal injection of methotrexate. The patient remains alive without recurrence 4 years later. Awareness of primary breast lymphoma is essential for accurate and timely diagnosis and avoidance of unnecessary surgery.}, } @article {pmid33191115, year = {2021}, author = {Shah, OS and Soran, A and Sahin, M and Knapick, BA and Ugras, S and Celik, E and Lucas, PC and Lee, AV}, title = {Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.}, journal = {Clinical breast cancer}, volume = {21}, number = {3}, pages = {210-217}, doi = {10.1016/j.clbc.2020.08.009}, pmid = {33191115}, issn = {1938-0666}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/genetics ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {BACKGROUND: Identification of genomic alterations present in cancer patients may aid in cancer diagnosis, prognosis and therapeutic target discovery. In this study, we aimed to identify clinically actionable variants present in stage IV breast cancer (BC) samples.

MATERIALS AND METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of BC (n = 41). DNA was sequenced using MammaSeq, a BC-specific next-generation sequencing panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data, and the resulting single nucleotide variants were annotated using the CRAVAT toolkit. Single nucleotide variations (SNVs) were filtered to remove common polymorphisms and germline variants. CNVkit was employed to identify copy number variations (CNVs). The Precision Medicine Knowledgebase (PMKB) and OncoKB Precision Oncology Database were used to associate clinical significance with the identified variants.

RESULTS: A total of 41 samples from Turkish patients with BC were sequenced (read depth of 94-13,340; median of 1529). These patients were diagnosed with various BC subtypes including invasive ductal carcinoma, invasive lobular carcinoma, apocrine BC, and micropapillary BC. In total, 59 different alterations (49 SNVs and 10 CNVs) were identified. From these, 8 alterations (3 CNVs - ERBB2, FGFR1, and AR copy number gains and 5 SNVs - IDH1.R132H, TP53.E204∗, PI3KCA.E545K, PI3KCA.H1047R, and PI3KCA.R88Q) were identified to have some clinical significance by PMKB and OncoKB. Moreover, the top 5 genes with the most SNVs included PIK3CA, TP53, MAP3K1, ATM, and NCOR1. Additionally, copy number gains and losses were found in ERBB2, GRB7, IGFR1, AR, FGFR1, MYC, and IKBKB, and BRCA2, RUNX1, and RB1, respectively.

CONCLUSION: We identified 59 unique alterations in 38 genes in 41 stage IV BC tissue samples using MammaSeq[TM]. Eight of these alterations were found to have some clinical significance by OncoKB and PKMB. This study highlights the potential use of cancer specific next-generation sequencing panels in clinic to get better insight into the patient-specific genomic alterations.}, } @article {pmid33186270, year = {2020}, author = {Le, VT and Wong, FC and Bassett, RL and Whitman, GJ}, title = {A Comparison of the Diagnostic Value of Positron Emission Tomography/Computed Tomography and Ultrasound for the Detection of Metastatic Axillary Nodal Disease in Treatment-Naive Breast Cancer.}, journal = {Ultrasound quarterly}, volume = {37}, number = {1}, pages = {28-33}, pmid = {33186270}, issn = {1536-0253}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymphatic Metastasis ; Multimodal Imaging ; *Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; }, abstract = {The objective of this study was to describe the diagnostic value of positron emission tomography/computed tomography (PET/CT) and ultrasound (US) for identifying metastatic axillary disease in primary breast cancer. This is a retrospective review of 240 patients with treatment-naive unilateral primary breast cancer of at least stage T2. Eighty-five patients met our inclusion criteria. Initial whole-body PET/CT and axillary US examinations were reviewed and compared with the criterion standard of fine-needle aspiration cytology. Sensitivity, accuracy, and positive predictive value (PPV) for each modality were computed. Because of all positive US cases, specificity and negative predictive value of US were not determined. Sensitivity and accuracy between modalities were compared using McNemar test. The majority of the patients were White women with clinical inflammatory breast cancer and with histologically invasive ductal carcinoma. The most common tumor and nodal stage was T4N3. The tumors were predominantly estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 negative. The sensitivities of PET/CT and US were 96.2% and 100%, respectively. The accuracies for PET/CT and US were 91.8% and 94.1%, respectively. The PPV for PET/CT was 95.1%, and for US, the PPV was 94.1%. No significant difference in sensitivity or accuracy was shown between PET/CT and US for the diagnosis of metastatic axillary nodal disease. Three of 85 cases showed discordance between negative PET/CT and positive US and fine-needle aspiration cytology.}, } @article {pmid33179556, year = {2020}, author = {Zheng, J and Yu, J and Zhou, T}, title = {Clinical characteristics of breast ductal carcinoma in situ with microinvasion: a narrative review.}, journal = {The Journal of international medical research}, volume = {48}, number = {11}, pages = {300060520969304}, pmid = {33179556}, issn = {1473-2300}, mesh = {*Breast Neoplasms/diagnosis ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Humans ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; }, abstract = {Ductal carcinoma in situ (DCIS) with microinvasion (DCIS-MI) is defined as the extension of cancer cells beyond the basement membrane into adjacent tissue with no focus larger than 1 mm or a maximum diameter of less than 1 mm for multiple invasive foci. DCIS-MI constitutes approximately 1% of all breast cancer cases and 5% to 10% of cases of DCIS. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, diagnosis, treatment, and prognosis of DCIS-MI.}, } @article {pmid33173683, year = {2020}, author = {Tsuruta, Y and Miyashita, H and Kuramoto, Y and Karakawa, R and Suesada, N and Shibata, T and Yoshimatsu, H and Yano, T}, title = {An Idea of Hemi-abdominal Free Flap for Breast Reconstruction: A Case Report.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {8}, number = {10}, pages = {e3168}, pmid = {33173683}, issn = {2169-7574}, abstract = {A deep inferior epigastric perforator (DIEP) flap is one of the gold standards for autologous breast reconstructions. However, this flap cannot be chosen again if asynchronous contralateral breast cancer occurs in the future. To solve this problem, we propose an idea and design for a hemi-abdominal DIEP flap. The patient was a 50-year-old woman who was suffering from right invasive ductal carcinoma. In using a hemi-abdominal DIEP flap, the poor postoperative appearance of the donor site might be a problem. To obtain a good donor site shape, we use a specific design to make the appearance of the donor site as good as possible. Specifically, we make an oblique spindle-shaped flap that can cover the deep inferior epigastric perforators, the superficial circumflex iliac artery, and the superficial inferior epigastric artery and avoid dog-ears, without passing over the median line. The flap weight was 800 g, the operating time was 6 hours and 22 minutes, and the bleeding amount was 110 ml. The patient had a minor wound infection in the donor site, and it was treated with a local wound treatment. The patient is satisfied with the result. We believe our flap design could minimize the unfavorable appearance of the donor site. This method might be suited to cases where the patients present with excess skin and fat on the abdomen, and half the abdominal tissue is enough to create the necessary volume of the breast. Although more cases and studies will be required to justify our technique, this case may show the possibility of a new option for breast reconstructions.}, } @article {pmid33173478, year = {2020}, author = {Kashu, N and Oura, S and Yoshida, H and Nishino, E and Makimoto, S}, title = {A Case of Squamous Cell Carcinoma of the Breast with Low-Grade Adenosquamous Carcinoma.}, journal = {Case reports in oncology}, volume = {13}, number = {3}, pages = {1152-1157}, pmid = {33173478}, issn = {1662-6575}, abstract = {A 68-year-old woman with a breast mass was referred to our hospital. Imaging studies showed an oval well-defined mass, 1.3 cm in size, in her left lower outer quadrant of the breast. Core needle biopsy with immunohistochemical staining showed atypical spindle cells forming solid nests with necrosis and papillary lesions, leading to the tentative and pre-operative diagnosis of invasive ductal carcinoma. Due to the absence of daughter nodules, extensive ductal spread, and lymphadenopathy on imaging evaluation, the patient underwent breast-conserving surgery and sentinel node biopsy, resulting in negative surgical margins and no lymph node involvement. Post-operative pathological examination showed triple negative atypical cells with squamous differentiation, squamous cell carcinoma (SCC), with cystic parts and a small amount of low-grade adenosquamous cell carcinoma (LGASC), both encompassing the cystic parts in a contiguous fashion. No cases with synchronous SCC and LGASC in the breast have been reported to date. An etiologic correlation between SCC and LGASC should be further evaluated.}, } @article {pmid33167552, year = {2020}, author = {Dimitrov, KC and Song, S and Chang, H and Lim, T and Lee, Y and Kwak, BJ}, title = {Interdigital Capacitor-Based Passive LC Resonant Sensor for Improved Moisture Sensing.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {21}, pages = {}, pmid = {33167552}, issn = {1424-8220}, abstract = {Herein, a passive low-profile moisture sensor design based on radio frequency identification (RFID) technology is proposed. The sensor consists of an LC resonant loop, and the sensing mechanism is based on the fringing electric field generated by the capacitor in the circuit. A standard planar inductor and a two-layer interdigital capacitor (IDC) with a significantly higher fringing capacitance compared to that of a conventional parallel plate capacitor (PPC) are used, resulting in improved frequency offset and sensitivity of the sensor. Furthermore, a sensor tag was designed to operate at an 8.2 MHz electronic article surveillance (EAS) frequency range and the corresponding simulation results were experimentally verified. The IDC- and PPC-based capacitor designs were comprehensively compared. The proposed IDC sensor exhibits enhanced sensitivity of 10% in terms of frequency offset that is maintained over time, increased detection distance of 5%, and more than 20% increase in the quality factor compared to sensors based on PPC. The sensor's performance as a urine detector was experimentally qualified. Additionally, it was shown experimentally that the proposed sensor shows a faster response to moisture. Both simulation and experimental data are presented and elucidated herein.}, } @article {pmid33164285, year = {2021}, author = {Homma, MK and Kiko, Y and Hashimoto, Y and Nagatsuka, M and Katagata, N and Masui, S and Homma, Y and Nomizu, T}, title = {Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas.}, journal = {Cancer science}, volume = {112}, number = {2}, pages = {619-628}, pmid = {33164285}, issn = {1349-7006}, support = {20lm0203006j0004//Japan Agency for Medical Research and Development/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Casein Kinase II/*metabolism ; Cell Nucleolus/enzymology ; Cell Nucleus/enzymology ; Female ; Humans ; MCF-7 Cells ; Middle Aged ; Prognosis ; }, abstract = {Overexpression of the ubiquitous protein kinase, CK2α, has been reported in various human cancers. Here, we demonstrate that nuclear and nucleolar CK2α localization in invasive ductal carcinomas of the breast is a reliable predictor of poor prognosis. Cellular localization of CK2α in nuclei and nucleoli was analyzed immunohistochemically using surgical tissue blocks from 112 patients, who had undergone surgery without neoadjuvant chemotherapy. Clinical data collection and median follow-up period were for more than 5 y. In total, 93.8% of patients demonstrated elevated CK2α expression in nuclei and 36.6% of them displayed elevated expression predominantly in nucleoli. Clinicopathological malignancy was strongly correlated with elevated nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly worse (P = .0002) in patients with positive nucleolar CK2α staining. The 5-y survival rate decreased to a roughly 50% in nucleolar CK2α-positive patients of triple-negative (P = .0069) and p Stage 3 (P = .0073) groups. In contrast, no patients relapsed or died in the triple-negative group who exhibited a lack of nucleolar CK2α staining. Evaluation of nucleolar CK2α staining showed a high secondary index with a hazard ratio of 6.629 (P = .001), following lymph node metastasis with a hazard ratio of 14.30 (P = .0008). Multivariate analysis demonstrated that nucleolar CK2α is an independent factor for recurrence-free survival. Therefore, we propose that histochemical evaluation of nucleolar CK2α-positive staining may be a new and robust prognostic indicator for patients who need further treatment. Functional consequences of nucleolar CK2 dysfunction may be a starting point to facilitate development of novel treatments for invasive breast carcinoma.}, } @article {pmid33163280, year = {2020}, author = {Zhang, J and Sun, M and Chang, E and Lu, CY and Chen, HM and Wu, SY}, title = {Pathologic response as predictor of recurrence, metastasis, and survival in breast cancer patients receiving neoadjuvant chemotherapy and total mastectomy.}, journal = {American journal of cancer research}, volume = {10}, number = {10}, pages = {3415-3427}, pmid = {33163280}, issn = {2156-6976}, abstract = {To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in breast invasive ductal carcinoma (IDC) patients receiving neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we used the pathologic response (PR) of primary breast diseases (T stages), nodal diseases (N stages), and combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) based on existing clinical and pathologic reports as predictors. We enrolled patients with IDC who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) of PR; other independent predictors were controlled for or stratified in the analysis. We analyzed 3654 IDC patients (1031, 1215, 1003, and 405 patients with clinical stages IIB, IIIA, IIIB, and IIIC, respectively) receiving NACT and TM. After multivariate Cox regression analyses, the adjusted HRs (aHRs) (95% CI) for all-cause mortality, LRR, and DM were noted to be 0.21 (0.13-0.34), 0.19 (0.08-0.48), and 0.33 (0.23-0.47), respectively, for pCR; 0.56 (0.48-0.65), 0.67 (0.51-0.89), and 0.61 (0.52-0.70), respectively, for AJCC downstaging; and 1.85 (1.56-2.18), 1.17 (0.84-1.62), and 1.61 (1.36-1.90), respectively, for AJCC upstaging. The PR parameters used in the study are easily applied because they are based on existing staging records, and they can strongly predict OS, LRR, and DM in IDC patients receiving NACT and TM, regardless of clinical stage. The results can be used to guide adjuvant treatment.}, } @article {pmid33163131, year = {2021}, author = {Chung, HL and Leung, JWT}, title = {Breast cancer recurrences in myocutaneous flap reconstruction.}, journal = {Radiology case reports}, volume = {16}, number = {1}, pages = {40-46}, pmid = {33163131}, issn = {1930-0433}, abstract = {Autologous flap reconstruction is widely used after skin sparing mastectomy to reconstruct the appearance of the breast. We present 2 cases of breast cancer recurrence in a deep inferior epigastric perforator reconstruction, including a 65-year-old female with history of papillary carcinoma and a 35-year-old female with history of a high grade invasive ductal carcinoma with extensive ductal carcinoma in situ. Differential imaging considerations of the post mastectomy patient are reviewed. Typical appearance of a deep inferior epigastric perforator flap reconstruction as well as location and timing of presentation may help differentiate a recurrence from the more commonly encountered postsurgical etiologies.}, } @article {pmid33159966, year = {2021}, author = {Lin, LH and Ozerdem, U and Cotzia, P and Lee, J and Chun, J and Schnabel, F and Darvishian, F}, title = {Upgrade rate of intraductal papilloma diagnosed on core needle biopsy in a single institution.}, journal = {Human pathology}, volume = {110}, number = {}, pages = {43-49}, doi = {10.1016/j.humpath.2020.10.012}, pmid = {33159966}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/methods ; Biopsy, Large-Core Needle/methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Hyperplasia/pathology ; Middle Aged ; Papilloma, Intraductal/diagnosis/*pathology/*surgery ; Retrospective Studies ; Young Adult ; }, abstract = {The management of intraductal papilloma (IDP) diagnosed on core needle biopsy (CNB) is controversial due to the variable upgrade rates to breast carcinoma (BC) on subsequent surgical excision reported in the literature. The purpose of our study was to investigate the upgrade rate of IDP diagnosed on CNB to BC in subsequent surgical excision and the impact of clinical, pathologic, and radiologic variables. This is a retrospective cohort of all women who had a diagnosis of IDP on a CNB between 2005 and 2018 in a tertiary academic center with subsequent surgical excision. Upgrade was defined as ductal carcinoma in situ (DCIS) and invasive carcinoma on surgical excision. Statistical analyses included Pearson's chi-square, Wilcoxon rank-sum, and logistic regression. A total of 216 women with IDP in a CNB were included. Nineteen patients (8.8%) upgraded to BC in the overall cohort, including 14 DCIS and 5 invasive carcinomas. An upgrade rate of 27% was found in atypical IDP (14 of 51 cases), while only 3% of pure IDP upgraded to BC (5 of 165 cases). Older age (>53 years) at the time of biopsy (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.01-1.09, p = 0.027) and concomitant atypical ductal hyperplasia (ADH) (OR = 9.69, 95% CI = 3.37-27.81, p < 0.0001) were significantly associated with upgrade. Our results support surgical excision of IDP on CNB when associated with ADH or diagnosed in women aged older than 53 years. The low surgical upgrade rate of 3% for pure IDP on CNB in younger women should be part of the management discussion.}, } @article {pmid33154305, year = {2020}, author = {Singh, V and Kaur, N and Mandal, S and Mallya, V and Tomar, R and Khurana, N and Bains, L}, title = {Neuroendocrine carcinomas of the breast: Case series with review of literature.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {4}, pages = {559-563}, doi = {10.4103/IJPM.IJPM_908_19}, pmid = {33154305}, issn = {0974-5130}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/classification/*pathology ; Carcinoma, Neuroendocrine/*pathology ; Female ; Histological Techniques ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: The breast tumors with neuroendocrine differentiation show features similar to their counterparts in other organs. Neuroendorine carcinomas account for less than 0.1% of all breast carcinomas.

AIMS: To study the demographics and clinicopathological prameters ten cases showing neuroendocrine carcinoma breast. Material and Methods: Ten cases showing neuroendocrine carcinoma were studied. The data was analysed for demographics and clinicopathological prameters. The Immunohistochemistry for ER, PR, Her2neu, Synaptophysin, Chromogranin, NSE, Ki67 index and EMA were done in these cases.

RESULTS: Nine Trucut biopsies were reported as infiltrating duct carcinoma and one case as IDC with neuroendocrine differentiation with focal mucinous areas.The histopathological slides of breast excision specimens revealed clusters of cells arranged in sheets and small nests separated by thin fibrous septae in eight of the cases. Trabeculae were noted in two case and in another rosettes were noted. DCIS component was noted in two cases. Infiltration into fat in five of the cases. One case showed pools of mucin. The tumour cells were positive for synaptophysin in 5/10 cases, chromogranin in 8/10 cases and NSE in 9/10 cases. Estrogen receptor positivity was noted 6 cases (6/10), progesterone receptor positivity in 8 cases (8/10) and Her2neu positivity in 5 cases (5/10).

CONCLUSION: NECB cases are more likely to ER/PR positive with variability of expression of neuroendocrine markers. These tumors are more aggressive with propensity for distant metastasis. Endocrine therapy may be more beneficial than standard chemotherapy. Anti-angiogenic markers are an exciting new approach for these case, which is yet to be explored.}, } @article {pmid33154304, year = {2020}, author = {Oral, O and Unverdi, H and Kumcu, E and Turkbey, D and Dogan, S and Hucumenoglu, S}, title = {Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {4}, pages = {551-558}, doi = {10.4103/IJPM.IJPM_637_18}, pmid = {33154304}, issn = {0974-5130}, mesh = {Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mucin 5AC/*genetics ; Mucin-1/*genetics ; Mucin-2/*genetics ; Mucin-6/*genetics ; Prognosis ; }, abstract = {AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters.

MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas.

RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion.

CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.}, } @article {pmid33149700, year = {2020}, author = {Bendardaf, R and Saheb Sharif-Askari, F and Saheb Sharif-Askari, N and Yousuf Guraya, S and A AlMadhi, S and Abusnana, S}, title = {Incidence and Clinicopathological Features of Breast Cancer in the Northern Emirates: Experience from Sharjah Breast Care Center.}, journal = {International journal of women's health}, volume = {12}, number = {}, pages = {893-899}, pmid = {33149700}, issn = {1179-1411}, abstract = {BACKGROUND: Breast cancer is the most frequently reported cancer among women in the Middle East and North Africa (MENA) region. However, the available data about women breast cancer from the MENA and particularly from the Northern Emirates region of the United Arab Emirates (UAE) are scarce and inconsistent. Therefore, this study estimated the incidence, patient-specific factors including 25(OH)D levels, and clinicopathological features of breast cancer in women from the Northern Emirates.

METHODS: We conducted this retrospective case-control study on 1,048 women who were referred to the Sharjah Breast Care Centre at University Hospital Sharjah between March 2016 and July 2018. Multivariate logistic regression was used for the statistical analysis of clinical data.

RESULTS: Out of 1048 women with breast-related conditions referred to our canter, 94 (10%) were diagnosed with breast cancer (1 in 11), and approximately 1 in 5 of these women was younger than 40 years. After adjusting for age, body mass index and menopause status, women with serum 25-hydroxyvitamin D [25(OH)D] levels lower than 20 ng/mL were found to be at higher risk of breast cancer (odd ratio, 4.63; 95% CI, 2.61-8.23). The majority of breast cancer cases had invasive-ductal carcinoma with hormone-positive receptor molecular subtype (78 cases out of 94, 83%). HER2 overexpressing tumor (3+ by immunohistochemistry (IHC) or by fluorescence in situ hybridization (FISH)) was seen more in women younger than 40 years as compared to older women (7 cases out of 19 HER2 expressed tumors, p=0.007).

CONCLUSION: Our study cohort showed a mean age of diagnosis of breast cancer in women a decade earlier than in the developed countries. Furthermore, women with breast cancer tend to be serum 25(OH)D deficient at diagnosis and to have luminal A tumors.}, } @article {pmid33148767, year = {2020}, author = {Young, HML and March, DS and Highton, PJ and Graham-Brown, MPM and Churchward, DC and Grantham, C and Goodliffe, S and Jones, W and Cheung, MM and Greenwood, SA and Eborall, HC and Conroy, S and Singh, SJ and Smith, AC and Burton, JO}, title = {Exercise for people living with frailty and receiving haemodialysis: a mixed-methods randomised controlled feasibility study.}, journal = {BMJ open}, volume = {10}, number = {11}, pages = {e041227}, pmid = {33148767}, issn = {2044-6055}, support = {CS-2013-13-014/DH_/Department of Health/United Kingdom ; DRF-2016-09-015/DH_/Department of Health/United Kingdom ; }, mesh = {Accidental Falls ; Adult ; Exercise ; Exercise Therapy ; Feasibility Studies ; Female ; *Frailty ; Humans ; Male ; Quality of Life ; Renal Dialysis ; }, abstract = {OBJECTIVES: Frailty is highly prevalent in haemodialysis (HD) patients, leading to poor outcomes. This study aimed to determine whether a randomised controlled trial (RCT) of intradialytic exercise is feasible for frail HD patients, and explore how the intervention may be tailored to their needs.

DESIGN: Mixed-methods feasibility.

SETTING AND PARTICIPANTS: Prevalent adult HD patients of the CYCLE-HD trial with a Clinical Frailty Scale Score of 4-7 (vulnerable to severely frail) were eligible for the feasibility study.

INTERVENTIONS: Participants in the exercise group undertook 6 months of three times per week, progressive, moderate intensity intradialytic cycling (IDC).

OUTCOMES: Primary outcomes were related to feasibility. Secondary outcomes were falls incidence measured from baseline to 1 year following intervention completion, and exercise capacity, physical function, physical activity and patient-reported outcomes measured at baseline and 6 months. Acceptability of trial procedures and the intervention were explored via diaries and interviews with n=25 frail HD patients who both participated in (n=13, 52%), and declined (n=12, 48%), the trial.

RESULTS: 124 (30%) patients were eligible, and of these 64 (52%) consented with 51 (80%) subsequently completing a baseline assessment. n=24 (71% male; 59±13 years) dialysed during shifts randomly assigned to exercise and n=27 (81% male; 65±11 years) shifts assigned to usual care. n=6 (12%) were lost to follow-up. The exercise group completed 74% of sessions. 27%-89% of secondary outcome data were missing. Frail HD patients outlined several ways to enhance trial procedures. Maintaining ability to undertake activities of daily living and social participation were outcomes of primary importance. Participants desired a varied exercise programme.

CONCLUSIONS: A definitive RCT is feasible, however a comprehensive exercise programme may be more efficacious than IDC in this population.

TRIAL REGISTRATION NUMBERS: ISRCTN11299707; ISRCTN12840463.}, } @article {pmid33148662, year = {2021}, author = {Chen, F and Ding, K and Priedigkeit, N and Elangovan, A and Levine, KM and Carleton, N and Savariau, L and Atkinson, JM and Oesterreich, S and Lee, AV}, title = {Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells.}, journal = {Cancer research}, volume = {81}, number = {2}, pages = {268-281}, pmid = {33148662}, issn = {1538-7445}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/genetics/metabolism ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Cadherins/antagonists & inhibitors/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Prognosis ; Single-Cell Analysis/*methods ; *Transcriptome ; Tumor Cells, Cultured ; }, abstract = {Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. SIGNIFICANCE: This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.}, } @article {pmid33148628, year = {2022}, author = {Pareja, F and Vahdatinia, M and Marchio, C and Lee, SSK and Da Cruz Paula, A and Derakhshan, F and da Silva, EM and Selenica, P and Dopeso, H and Chandarlapaty, S and Wen, HY and Vincent-Salomon, A and Brogi, E and Weigelt, B and Reis-Filho, JS}, title = {Neuroendocrine tumours of the breast: a genomic comparison with mucinous breast cancers and neuroendocrine tumours of other anatomic sites.}, journal = {Journal of clinical pathology}, volume = {75}, number = {1}, pages = {10-17}, pmid = {33148628}, issn = {1472-4146}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; Female ; Genomics ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neuroendocrine Tumors/*genetics/pathology ; Pancreatic Neoplasms/*genetics/pathology ; Receptors, Estrogen/genetics ; Transcription Factors/genetics ; *Transcriptome ; Exome Sequencing ; }, abstract = {AIMS: Breast neuroendocrine tumours (NETs) constitute a rare histologic subtype of oestrogen receptor (ER)-positive breast cancer, and their definition according to the WHO classification was revised in 2019. Breast NETs display histologic and transcriptomic similarities with mucinous breast carcinomas (MuBCs). Here, we sought to compare the repertoire of genetic alterations in breast NETs with MuBCs and NETs from other anatomic origins.

METHODS: On histologic review applying the new WHO criteria, 18 breast tumours with neuroendocrine differentiation were reclassified as breast NETs (n=10) or other breast cancers with neuroendocrine differentiation (n=8). We reanalysed targeted sequencing or whole-exome sequencing data of breast NETs (n=10), MuBCs type A (n=12) and type B (n=11).

RESULTS: Breast NETs and MuBCs were found to be genetically similar, harbouring a lower frequency of PIK3CA mutations, 1q gains and 16q losses than ER-positive/HER2-negative breast cancers. 3/10 breast NETs harboured the hallmark features of ER-positive disease (ie, PIK3CA mutations and concurrent 1q gains/16q losses). Breast NETs showed an enrichment of oncogenic/likely oncogenic mutations affecting transcription factors compared with common forms of ER-positive breast cancer and with pancreatic and pulmonary NETs.

CONCLUSIONS: Breast NETs are heterogeneous and are characterised by an enrichment of mutations in transcription factors and likely constitute a spectrum of entities histologically and genomically related to MuBCs. While most breast NETs are distinct from ER-positive/HER2-negative IDC-NSTs, a subset of breast NETs appears to be genetically similar to common forms of ER-positive breast cancer, suggesting that some breast cancers may acquire neuroendocrine differentiation later in tumour evolution.}, } @article {pmid33140128, year = {2021}, author = {Chen, XY and Thike, AA and Koh, VCY and Nasir, NDM and Bay, BH and Tan, PH}, title = {Breast ductal Carcinoma in situ associated with microinvasion induces immunological response and predicts ipsilateral invasive recurrence.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {478}, number = {4}, pages = {679-686}, pmid = {33140128}, issn = {1432-2307}, support = {SHF/FG668S/2015//SingHealth Foundation/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*immunology/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*immunology/metabolism/*pathology/prevention & control ; Prognosis ; Proportional Hazards Models ; }, abstract = {Although microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and established invasive ductal carcinoma, survival outcomes and biological behaviour of DCIS-Mi are still poorly understood. This study investigated the potential influence of Mi on disease-free survival (DFS) and assessed its correlations with clinicopathological parameters, prognosis, molecular, and immune markers. CD4, CD8, forkhead box P3 (FOXP3), CD68, CD163, programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression in pure DCIS and DCIS-Mi, from a cohort of 198 patients, were determined by immunohistochemistry. DFS, clinicopathological parameters, immune markers, and biomarker expression were correlated with presence of Mi. Twelve out of 198 DCIS cases were associated with Mi. DCIS-Mi was significantly linked with ipsilateral invasive recurrence (p = 0.032). Kaplan-Meier analysis revealed that DCIS-Mi had worse DFS for ipsilateral invasive recurrence (p = 0.011) and this was affirmed by multivariate Cox regression analysis (95% CI 1.181-9.010, HR = 3.262, p = 0.023). DCIS-Mi was associated with higher densities of immune infiltrates positive for CD4 (p = 0.037), FOXP3 (p = 0.037), CD163 (p = 0.01), and PD-L1 (p = 0.015). This study demonstrated that DCIS-Mi was correlated with high densities of immune infiltrates and predicted ipsilateral invasive recurrence.}, } @article {pmid33137841, year = {2020}, author = {Woodward, S and Willis, A and Lazar, M and Berger, AC and Tsangaris, T}, title = {Nipple-sparing mastectomy: A review of outcomes at a single institution.}, journal = {The breast journal}, volume = {26}, number = {11}, pages = {2183-2187}, doi = {10.1111/tbj.14088}, pmid = {33137841}, issn = {1524-4741}, mesh = {*Breast Neoplasms/surgery ; Female ; Follow-Up Studies ; Humans ; Male ; *Mammaplasty ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; Nipples/surgery ; Organ Sparing Treatments ; Retrospective Studies ; }, abstract = {Nipple-sparing mastectomy (NSM) offers patients who are not candidates for breast-conserving treatment an aesthetically pleasing alternative to traditional mastectomy. Some studies have demonstrated its oncologic safety while others have demonstrated residual occult tumor cells at the nipple-areolar complex (NAC). These data prompt further review of oncologic outcomes after NSM.A single institution retrospective chart review was performed of all NSMs performed by 4 breast surgeons at Thomas Jefferson University Hospital over a span of 2012-2019. In this cohort, we review the reconstruction performed, axillary lymph node status, surgical margins, final pathology, loss of the NAC, recurrence rates, and follow-up. In our cohort, we reviewed 170 NSMs performed on 105 patients. All patients were female, and the average age was 46.9 years. Prophylactic procedures were performed on 43% of patients with 17.1% of patients being BRCA positive. Of those undergoing NSM for cancer (n = 94), the associated pathology was 28.8% DCIS, 32.9% IDC, and 3.5% ILC (this accounts for some patients with multiple diagnoses on final pathology). Sentinel lymph node biopsy (SLNB) was performed in 52.9% of cases with 10.6% of cases being positive for axillary disease. Margins were positive in 10.6% (n = 10) of cases performed for cancer with 8.5% (n = 8) of cases having positive margin at the NAC and the remainder being at the deep margin. Based on margin positivity, 2.4% (n = 4) of patients underwent redo surgery with 1 patient requiring re-resection at the NAC margin and 3 patients having total NAC resection. Total loss of NAC occurred in 5.9% (n = 10) of cases due to positive margins (n = 3) and necrosis (n = 7). Recurrence occurred in 7.2% (n = 7) of cases who underwent NSM for cancer. Locoregional recurrence in breast tissue, skin, or axilla occurred in 4.1% (n = 4) of cases with 0 recurrences at the NAC. Distant recurrence occurred in 4.1% (n = 4) of cases at both liver and bone. Average time to recurrence was 27.3 months. Of the 170 NSM performed, 98% had immediate tissue expander placement with 60% converting to permanent subpectoral implant reconstruction, 14% latissimus dorsi flap reconstruction, 0.6% delayed deep inferior epigastric artery perforator free-flap reconstruction, and 5.2% undergoing delayed free transversus abdominus muscle flap reconstruction. Of all the cases reviewed, there was only 1 death. Our average follow-up was 26.7 months. We demonstrate similar numbers in our analysis as other studies that have looked at oncologic outcomes after NSM. Although we demonstrate evidence of occult disease at the NAC margin when performing NSM, there was no evidence of recurrence at the NAC demonstrating its efficacy and safety. With proper patient selection, this procedure can be safely offered as an esthetically appealing alternative to traditional mastectomy.}, } @article {pmid33136445, year = {2020}, author = {Qian, L and Fei, Q and Zhang, H and Qiu, M and Zhang, B and Wang, Q and Yu, Y and Guo, C and Ren, Y and Mei, M and Zhang, L and Zhu, Y and Yang, B}, title = {lncRNA HOTAIR Promotes DNA Repair and Radioresistance of Breast Cancer via EZH2.}, journal = {DNA and cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1089/dna.2020.5771}, pmid = {33136445}, issn = {1557-7430}, abstract = {Mounting evidence shows that long noncoding RNAs play important roles in human diseases and radioresistance could be an important factor for tumor recurrence. We observed that HOX antisense intergenic RNA (HOTAIR) expression increased in invasive ductal carcinoma (IDC) tissue. The irradiation effect of HOTAIR was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, cell cycle and apoptosis analysis, and xenografts in nude mice. Western blot, RNA pulldown assay, and RNA immunoprecipitation were used for mechanistic studies. HOTAIR, upregulated in IDC of breast cancer tissue, could promote breast cancer cell proliferation by regulating cell cycle and apoptosis. Overexpression of HOTAIR promoted DNA damage repair factors KU70, KU80, DNA-PKs, and ATM expression, and these could be impeded by small molecular inhibitors of enhancer of zeste homolog 2 (EZH2). Meanwhile, we found that HOTAIR could facilitate recruitment of EZH2 to the Avian Myelocytomatosis Viral Oncogene Homolog (MYC) promoter. HOTAIR is an important modulator not only to the prognostic of breast cancer, but also a good marker for radiotherapy.}, } @article {pmid33135196, year = {2021}, author = {Bishop, JA and Nakaguro, M and Whaley, RD and Ogura, K and Imai, H and Laklouk, I and Faquin, WC and Sadow, PM and Gagan, J and Nagao, T}, title = {Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.}, journal = {Histopathology}, volume = {79}, number = {3}, pages = {338-346}, pmid = {33135196}, issn = {1365-2559}, support = {P01 CA240239/CA/NCI NIH HHS/United States ; //UT Southwestern Medical Center/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Carcinoma, Ductal/diagnosis/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Mutation ; Oncogene Fusion ; Oxyphil Cells/pathology ; Proto-Oncogene Proteins B-raf/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/diagnosis/genetics/pathology ; Salivary Glands/pathology ; Sequence Analysis, RNA ; Transcription Factors/*genetics ; }, abstract = {AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.

METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.

CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.}, } @article {pmid33132109, year = {2021}, author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L}, title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.}, journal = {European urology focus}, volume = {7}, number = {5}, pages = {955-963}, doi = {10.1016/j.euf.2020.10.007}, pmid = {33132109}, issn = {2405-4569}, mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.}, } @article {pmid33132071, year = {2021}, author = {Sumodhee, S and Pujalte, M and Gal, J and Cham Kee, DL and Gautier, M and Schiappa, R and Chand, ME and Hannoun-Levi, JM}, title = {Accelerated partial breast irradiation in the elderly: 8-year oncological outcomes and prognostic factors.}, journal = {Brachytherapy}, volume = {20}, number = {1}, pages = {146-154}, doi = {10.1016/j.brachy.2020.08.012}, pmid = {33132071}, issn = {1873-1449}, mesh = {Aged ; Aged, 80 and over ; *Brachytherapy/methods ; *Breast Neoplasms/radiotherapy/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: The purpose of the study is to evaluate long-term clinical outcomes and prognostic factors after accelerated partial breast irradiation (APBI) in the elderly using high-dose-rate interstitial multicatheter brachytherapy (HIBT).

METHODS AND MATERIALS: Between 2005 and 2018, 109 patients underwent APBI using HIBT (34 Gy/10f/5d or 32 Gy/8f/4d). Based on a prospective database, outcomes were retrospectively analyzed (local relapse-free survival, metastatic-free survival, specific survival (SS), and overall survival (OS)). Prognostic factors were investigated. Late toxicity and cosmetic evaluation were reported.

RESULTS: With a median followup of 97 months [7-159], median age was 81.7 years [58-89]. In accordance with the GEC-ESTRO APBI classification, 72.5%, 11.9%, and 15.6% were classified as low, intermediate, and high risk, respectively. The histological type was mainly invasive ductal carcinoma (87.1%). The median tumor size was 10 mm [range 1-35]. Eight-year local relapse-free survival, SS, and OS were 96.7% [95% confidence interval (CI) [0.923; 1]), 96.7% [95% CI [0.924; 1], and 72% [95% CI [0.616; 0.837], respectively. In univariate analysis, APBI classification was not considered as prognostic factor, whereas molecular classification was prognostic factor for OS (p < 0.0001), SS (p = 0.007), and metastatic-free survival (p = 0.009) but not for local recurrence (p = 0.586). No Grade ≥3 late toxicity was observed, whereas 61 patients (88.4%) and 8 patients (11.6%) presented Grade 1 and 2 toxicities, respectively. The cosmetic outcome was excellent/good for 96.4%.

CONCLUSIONS: Long-term followup confirms that HIBT is safe and effective for elderly early breast cancer. Our results suggest that selected elderly women presenting with high-risk breast cancer could be also considered for APBI.}, } @article {pmid33130707, year = {2020}, author = {Kosaka, Y and Kikuchi, M and Nishimiya, H and Katoh, H and Kawaguchi, R and Araki, N and Shimazu, M and Tsumura, H and Waraya, M and Takada, F and Sengoku, N and Sangai, T}, title = {[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {9}, pages = {1387-1389}, pmid = {33130707}, issn = {0385-0684}, mesh = {*Breast Neoplasms/genetics/surgery ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating ; Child ; Female ; *Hereditary Breast and Ovarian Cancer Syndrome/genetics/surgery ; Humans ; Mastectomy ; }, abstract = {A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy(CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.}, } @article {pmid33130245, year = {2021}, author = {Zhang, Z and Rao, R and Mango, VL and Wilson-Gardner, P and Vempalle, S and Ojutiku, O}, title = {Presentation of self-detected breast mass in minority women with limited access to care: Can self-examination assist in early cancer detection?.}, journal = {Clinical imaging}, volume = {70}, number = {}, pages = {89-92}, pmid = {33130245}, issn = {1873-4499}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/diagnostic imaging ; Early Detection of Cancer ; Female ; Health Services Accessibility ; Humans ; *Mammography ; Mass Screening ; Retrospective Studies ; Self-Examination ; United States ; }, abstract = {OBJECTIVE: The United States Preventive Services Task Force recommends against breast self-examination. However, racial disparities exist in mammogram screening. We aimed to evaluate the presentation of women with newly diagnosed breast cancer in the underserved African-American and Hispanic community to provide insight regarding breast cancer screening in this population.

METHODS: This retrospective cohort study included women newly diagnosed with breast cancer from 1/1/2016 to 1/1/2018 in an inner city public community hospital. Data was collected via chart review. Patients were divided based on whether they presented with self-detected breast mass. Logistic regression was used for analysis.

RESULTS: 59 women were newly diagnosed with breast cancer. 34 women (58%) were African-American, 20 (34%) were Hispanic, and 5 (8%) were other race. Of 59 women, 36 (61%) presented with self-detected breast mass, and only 21 (36%) reported prior mammography. For women who presented with breast mass, the odds of having prior mammography were 78% lower (OR = 0.22, 95% CI 0.07-0.69, p = 0.009), while the odds of having invasive ductal carcinoma were 4.33 times higher (OR = 4.33, 95% CI 1.09-17.25, p = 0.037), as compared to the odds for women not presenting with breast mass.

CONCLUSION: Many of our newly diagnosed breast cancer patients were African-American or Hispanic women presenting with self-detected breast mass without prior screening mammography. Further studies should evaluate whether supplemental screening methods, such as breast self-examination or clinical examination, can help with early breast cancer detection in minority women with limited access to care, and such disparities should be considered by organizations when creating screening guidelines.}, } @article {pmid33126344, year = {2020}, author = {Liu, C and Wang, C and Du, Z and Xue, H and Liu, Z}, title = {Clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia.}, journal = {Medicine}, volume = {99}, number = {44}, pages = {e22904}, pmid = {33126344}, issn = {1536-5964}, mesh = {Age Factors ; Anticarcinogenic Agents/therapeutic use ; *Breast Neoplasms/drug therapy/pathology ; China/epidemiology ; Female ; Humans ; Imatinib Mesylate/*therapeutic use ; Incidence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/diagnosis/epidemiology/pathology ; Male ; Middle Aged ; *Neoplasms, Multiple Primary/blood/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Time Factors ; }, abstract = {This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.}, } @article {pmid33125923, year = {2020}, author = {Wang, K and Zhao, S and Jackson, E}, title = {Investigating exposure measures and functional forms in urban and suburban intersection safety performance functions using generalized negative binomial - P model.}, journal = {Accident; analysis and prevention}, volume = {148}, number = {}, pages = {105838}, doi = {10.1016/j.aap.2020.105838}, pmid = {33125923}, issn = {1879-2057}, mesh = {Accidents, Traffic/*statistics & numerical data ; Environment Design/*statistics & numerical data ; Forecasting/*methods ; Humans ; Models, Statistical ; Risk Assessment/methods/*statistics & numerical data ; Safety/*statistics & numerical data ; Suburban Population/*statistics & numerical data ; United States ; Urban Population/*statistics & numerical data ; }, abstract = {Selecting an appropriate exposure measure and functional form for Safety Performance Functions (SPFs) is critical in precisely predicting crash counts by different crash types for intersections. This study proposes a new approach, namely Generalized Negative Binomial-P (GNB-P) model, to model the complex relationship between crashes and different exposure measures by crash type for intersections, which helps not only identify the most reliable exposure measure for intersection SPFs, but also explore the most appropriate functional form of the NB models. To this end, three types of SPF functional forms, namely Power function, Hoerl function 1 and Hoerl function 2 with different exposure measures including major road AADT, minor road AADT and total AADT were estimated by crash type for stop-controlled and two types of signalized intersections. The over-dispersion of the SPF models was estimated using the exposure measures to account for crash data variation across different intersections. The SPF estimation results highlighted that the mean-variance structure of NB models is not consistent and varies by crash data. The over-dispersion of SPFs by crash type is not constant and varies across different intersections. The minor road AADT is shown to be positively correlated with the over-dispersion of SPFs in estimating crash counts for Same-Direction Crashes (SDC), Intersecting-Direction Crashes (IDC) and Single-Vehicle Crashes (SVC). Estimating the over-dispersion using exposure measures results in more reliable SPF results. Furthermore, it is found that the Power function with major road and minor road AADT as the exposure measure performs the best in estimating SPFs for Opposite-Direction Crashes (ODC). The Hoerl function 2 with total AADT and the proportion of minor road AADT over the total as the exposure measure performs the best in estimating SVC SPFs for intersections. The Hoerl function 1 with major road and minor road AADT as the exposure measure is more accurate in estimating SPFs for both SDC and IDC.}, } @article {pmid33125672, year = {2021}, author = {Sakamoto, N and Nashimoto, M and Nakagawa, M and Haruyama, Y and Koshida, Y and Fukuma, E}, title = {Skin grafting utilizing a skin of lateral thoracic area for chest wall reconstruction in patient who underwent mastectomy for locally advanced breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {28}, number = {2}, pages = {533-537}, pmid = {33125672}, issn = {1880-4233}, mesh = {Aged, 80 and over ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Axilla ; Biopsy ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal/drug therapy/pathology/*surgery ; Drug Combinations ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/pathology ; Mammaplasty/*methods ; Mastectomy/*methods ; Oxonic Acid/therapeutic use ; Skin Transplantation/*methods ; Surgical Flaps ; Tegafur/therapeutic use ; Thoracic Wall/*surgery ; Trastuzumab/therapeutic use ; Treatment Outcome ; }, abstract = {Locally advanced breast cancer sometimes results in a large chest wall defect at mastectomy. When closing the wound horizontally, the skin tension is usually severe in the middle of the wound, while the skin of the lateral area tends to make a dog-ear deformity. Triangle technique is a procedure to prevent the dog ear in which the skin and subcutaneous fat of the axilla are cut into an equilateral triangle. Herein, we present a case of breast cancer who underwent a mastectomy and closed the wound with a skin graft by utilizing the skin removed from lateral thoracic area using triangle technique. An 85-year-old female visited our institution complaining about the mass on her right breast. Preoperative images showed a 10 cm-sized mass with suspicious axillary and mediastinal lymph nodes swelling. A biopsy revealed a hormone receptor-negative, HER2-positive invasive ductal carcinoma. A mastectomy and axillary lymph node sampling were performed for a local control as the tumor did not respond to four cycles of triweekly trastuzumab combined with S-1. After a transverse elliptical incision, a skin of the lateral thoracic area was harvested using triangle technique. As the middle of the wound had excessive closing tension, the skin was grafted on the defect. After 10 day fixation by a tie-over dressing, the wound healed without complications. This procedure is a simple method for closing a large defect after mastectomy preventing both the dog-ear deformity and a new wound scarring of a donor site.}, } @article {pmid33125331, year = {2021}, author = {Martini, E and Cesini, I and D'Abbraccio, J and Arnetoli, G and Doronzio, S and Giffone, A and Meoni, B and Oddo, CM and Vitiello, N and Crea, S}, title = {Increased Symmetry of Lower-Limb Amputees Walking With Concurrent Bilateral Vibrotactile Feedback.}, journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society}, volume = {29}, number = {}, pages = {74-84}, doi = {10.1109/TNSRE.2020.3034521}, pmid = {33125331}, issn = {1558-0210}, mesh = {*Amputees ; Biomechanical Phenomena ; Feedback ; Gait ; Humans ; Pilot Projects ; Quality of Life ; Walking ; }, abstract = {Gait asymmetry in lower-limb amputees can lead to several secondary conditions that can decrease general health and quality of life. Including augmented sensory feedback in rehabilitation programs can effectively mitigate spatiotemporal gait irregularities. Such benefits can be obtained with non-invasive haptic systems representing an advantageous choice for usability in overground training and every-day life. In this study, we tested a wearable tactile feedback device delivering short-lasting (100ms) vibrations around the waist syncronized to gait events, to improve the temporal gait symmetry of lower-limb amputees. Three above-knee amputees participated in the study. The device provided bilateral stimulations during a training program that involved ground-level gait training. After three training sessions, participants showed higher temporal symmetry when walking with the haptic feedback in comparison to their natural walking (resulting symmetry index increases of +2.8% for Subject IDA, +12.7% for Subject IDB and +2.9% for Subject IDC). One subject retained improved symmetry (Subject IDB,+14.9%) even when walking without the device. Gait analyses revealed that higher temporal symmetry may lead to concurrent compensation strategies in the trunk and pelvis. Overall, the results of this pilot study confirm the potential utility of sensory feedback devices to positively influence gait parameters when used in supervised settings. Future studies shall clarify more precisely the training modalities and the targets of rehabilitation programs with such devices.}, } @article {pmid33123426, year = {2020}, author = {Roberts, JT and Digiacinto, W and Nguyen, QD}, title = {Pitfalls of Breast Evaluation in the Emergency Department.}, journal = {Cureus}, volume = {12}, number = {9}, pages = {e10612}, pmid = {33123426}, issn = {2168-8184}, abstract = {Breast complaints in the emergency department (ED) include trauma, infection, pain, masses, and nipple discharge. Breast cancer mimics other inflammatory conditions such as mastitis and abscess. Differentiating infectious processes versus cancer can become problematic when no imaging is used. While mammogram is included in the initial imaging for outpatient breast evaluation, ultrasound is more available in the ED. We present a case of a patient seen in the ED for breast pain and mass. The patient had no imaging done, yet the ED physician attempted to drain the mass unsuccessfully and prescribed antibiotics. The patient followed up at a breast center where clinical Stage IIA right breast invasive ductal carcinoma (IDC) was diagnosed. This case highlights the importance of breast imaging before drainage for suspected abscess and the importance of follow-up for all breast complaints that present in the ED to rule out a malignancy.}, } @article {pmid33118309, year = {2021}, author = {Peters, A and Cohen, N and Calhoun, P and Ruedy, KJ and Beck, RW and Martens, TW and Bao, S and Njeru, NM and Beck, SE and Price, DA}, title = {Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data.}, journal = {Diabetes, obesity & metabolism}, volume = {23}, number = {2}, pages = {631-636}, pmid = {33118309}, issn = {1463-1326}, mesh = {Aged ; Blood Glucose ; Blood Glucose Self-Monitoring ; *Diabetes Mellitus, Type 1 ; *Diabetes Mellitus, Type 2/drug therapy ; Female ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin ; Male ; Middle Aged ; }, abstract = {Basal insulin is often prescribed to patients with suboptimally controlled type 2 diabetes (T2D); however, its therapeutic efficacy is inadequate in many. During the MOBILE study's baseline phase, we evaluated 173 participants' continuous glucose monitoring (CGM) data (mean ± SD age 57 ± 9 years; 50% female; HbA1c 9.1% [range 7.1%-11.6%]; 40% using sulphonylureas; 19% using NPH; reported self-monitored blood glucose [SMBG] frequency median 1.0 checks/day) who were using basal, but not prandial insulin. Blinded CGM data were recorded for 10 days prior to randomization. The mean glucose value was 208 ± 47 mg/dL and it was lowest in the early morning. Mean time in the 70-180 mg/dL range was 9.6 ± 6.1 hours/day (40% ± 25%). Hyperglycaemia was extensive with medians of 14.7 (61%) and 5.0 (20.9%) hours/day with glucose greater than 180 and 250 mg/dL, respectively. Hypoglycaemia was infrequent (median [IQR] 0 [0, 4.3] minutes/day [0.0% {0.0%, 0.3%} ] with glucose less than 70 mg/dL). Blinded CGM highlights the limitations of infrequent SMBG in basal insulin users with T2D and allows characterization of hyperglycaemia and hypoglycaemia in basal insulin users with suboptimal control. The MOBILE study randomized phase will define the benefits of using real-time CGM compared with SMBG in this population.}, } @article {pmid33117849, year = {2020}, author = {Nguyen, CT and Olson, G and Pho, MT and Lew, AK and Pitrak, D and Saltzman, J and Hazra, A and Pursell, K and Pettit, NN}, title = {Automatic ID Consultation for Inpatients With COVID-19: Point, Counterpoint, and a Single-Center Experience.}, journal = {Open forum infectious diseases}, volume = {7}, number = {10}, pages = {ofaa318}, pmid = {33117849}, issn = {2328-8957}, abstract = {There are many unknowns with regard to COVID-19 clinical management, including the role of Infectious Diseases Consultation (IDC). As hospitalizations for COVID-19 continue, hospitals are assessing how to optimally and efficiently manage COVID-19 inpatients. Typically, primary teams must determine when IDC is appropriate, and ID clinicians provide consultation upon request of the primary team. IDC has been shown to be beneficial for many conditions; however, the impact of IDC for COVID-19 is unknown. Herein, we discuss the potential benefits and pitfalls of automatic IDC for COVID-19 inpatients. Important considerations include the quality of care provided, allocation and optimization of resources, and clinician satisfaction. Finally, we describe how automatic IDC changed throughout the COVID-19 pandemic at a single academic medical center.}, } @article {pmid33117685, year = {2020}, author = {Yu, J and Han, ZY and Li, T and Feng, WZ and Yu, XL and Luo, YC and Wu, H and Jiang, J and Wang, JD and Liang, P}, title = {Microwave Ablation Versus Nipple Sparing Mastectomy for Breast Cancer ≤5 cm: A Pilot Cohort Study.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {546883}, pmid = {33117685}, issn = {2234-943X}, abstract = {OBJECTIVES: Compared with nipple sparing mastectomy (NSM), microwave ablation (MWA) is one relatively new modality indicated for selected breast cancer with nipple sparing and with little of evidence-based medical research for decision-making. The objective of this study was to compare the effect of ultrasound-guided percutaneous MWA and NSM for breast cancer.

MATERIALS AND METHODS: A retrospective cohort study was conducted in a single institution from 2014 to 2020. Women with invasive ductal carcinoma of the breast ≤ 5cm treated by MWA or NSM were enrolled. The primary end point was tumor progression and secondary end points included survival, cosmetic results, and complications.

RESULTS: 21 patients in the MWA group and 43 in the NSM group were evaluated. The mean tumor size was 2.3 cm (range, 0.3-5.0 cm). Median follow-up was 26.7 months (range, 14.6-62.5 months). The mean age of MWA was 24 years older than that of the NSM group. All the patients achieved technique effectiveness. One local tumor progression and one ipsilateral breast recurrence occurred at 42 and 28 months after MWA, respectively. One ipsilateral breast recurrence and two bone metastasis occurred at 31.2, 34, and 30.5 months after NSM. Two groups had no significant difference in tumor progression (P = 0.16). No participants in both groups developed cancer related death (P > 0.99) and major complications (P > 0.99). However, MWA needed less hospitalization time (P < 0.001) and achieved better cosmetic results (P < 0.001).

CONCLUSIONS: MWA achieved similar short term effect for breast cancer control and better cosmetic satisfaction compared with NSM in selected patients. MWA provides appropriate option for elderly patients who are unfit for surgery.}, } @article {pmid33116614, year = {2020}, author = {Martuszewski, A and Paluszkiewicz, P and Nowak, M and Szewczyk, K and Staszek-Szewczyk, U}, title = {Triple Discordances in Receptor Status During Breast Cancer Local Progression and Metastases: Case Report and Literature Review.}, journal = {OncoTargets and therapy}, volume = {13}, number = {}, pages = {10343-10349}, pmid = {33116614}, issn = {1178-6930}, abstract = {Breast cancer is the most common female malignant neoplasm in Poland and around the world. Precise determination of tumor molecular profile allows application of appropriate anticancer therapy, increasing the chances of recovery. A 28-year-old woman detected a thickening in her left breast. Mammography showed a change measuring 60 mm (radiologically BIRADS 5). The biopsy revealed invasive ductal carcinoma, luminal subtype B, HER2 positive (cT3N1M0). Neoadjuvant chemotherapy was administered and then breast conserving surgery was performed. In postoperative histopathology cancer, biological subtype was evaluated: HER2 positive, nonluminal (ypT2ypN0cM0). Then, postoperative radiotherapy was performed. After 14 months, breast ultrasonography (US) and mammography (MGF) revealed the presence of suspicious changes (BIRADS 4). Tru-cut biopsy confirmed cancer recurrence (luminal subtype B, HER2 negative, ER negative, PgR: 10%, Ki-67: 70%). Despite implemented and modified chemotherapy regimens, local progression occurred. Genetic testing excluded BRCA gene mutation. The patient qualified for radical mastectomy modo Halsted (ypT4bN0cM0). Postoperative microscopic examination revealed triple negative breast invasive carcinoma of no special type. After 22 months, metastatic lesions in lungs and left retrosternal nodes appeared. Due to the limited possibilities of systemic treatment, the patient qualified for stereotactic radiotherapy of tumors in the lungs' and left retrosternal nodes. Advancement, histological type and molecular profile should be controlled at each stage of the disease, as they may change several times and require modification of therapy.}, } @article {pmid33112567, year = {2020}, author = {Utnal, PA and A, H and Pn, S and Gn, M}, title = {Expression of CD 133 in Invasive Ductal Carcinoma of Breast.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {10}, pages = {3055-3059}, pmid = {33112567}, issn = {2476-762X}, mesh = {AC133 Antigen/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: CD133 is a commonly used cancer stem cell (CSC) marker in breast cancer. However, the association between CD133 expression, with clinicopathological features and prognosis in breast cancer, is poorly understood in the Indian subcontinent. This study was designed to explore the expression of CD 133 in breast carcinoma and to know its association between CD133 and clinicopathological characteristics.

METHODS: A total of fifty seven cases were included in the study. All the clinicopathological parameters were collected from Department of Pathology archives. Slides, blocks, clinical information, tumor size and axillary lymph node status were obtained from medical records and the pathology reports. Immunohistochemistry was done using CD 133 antibodies. Both Cytoplasmic and membranous staining was taken a positive. Scoring was done based on percentage of positive cells and intensity of staining. MS Excel, SPSS version 22 (IBM SPSS Statistics, Somers NY, USA) was used to analyze data.p value < 0.05 was considered as statistically significant.

RESULTS: Statistically significant association between the CD 133 expression and nodal metastasis, tumor stage and Nottingham prognostic index was analysed. There was no statistical correlation between CD 133 expression age, tumor grade and tumor size. The disease free survival showed the mean disease free survival of CD 133 positivity cases was 16months. And the patients who were negative for CD 133 expression had mean survival of 30 months. By the Kaplan Mayer graph it was evident that the more the CD 133 expression the lesser was the disease free survival of the patients.

CONCLUSION: CD 133 expression was seen in 77.08% cases and was associated with tumor stage, lymph node metastasis, poor Nottingham prognostic index and  worse disease free survival. An increasing trend of association was seen between CD 133 expression and Age, Tumor Size and Tumor grade.
.}, } @article {pmid33112116, year = {2020}, author = {Köy, Y and Dirilenoglu, F and Tetikkurt, Ü and Muhammedoğlu, A and Çelik, A}, title = {Aldehyde dehydrogenase-1 positivity is associated with ER negativity in patients with invasive ductal carcinoma of the breast.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {71}, number = {3}, pages = {254-260}, doi = {10.5114/pjp.2020.99792}, pmid = {33112116}, issn = {1233-9687}, mesh = {Aldehyde Dehydrogenase 1 Family/*metabolism ; Biomarkers, Tumor ; *Breast Neoplasms ; *Carcinoma, Ductal, Breast ; Humans ; Mastectomy ; Prognosis ; }, abstract = {Cancer stem cells (CSCs) are self-renewable and can be differentiated into different cell types. They play an important role in oncogenic signaling pathways, tumor cell heterogeneity, metastasis, and therapeutic resistance. Aldehyde dehydrogenase 1 (ALDH1) was identified as a specific marker for breast CSCs. The study included a total of 105 patients with a diagnosis of invasive ductal carcinoma (IDC) who underwent mastectomy and with sufficient pathology material for histopathological examination. Patient demographics, tumor location, tumor diameter, the presence of lymphovascular and perineural invasion and lymph node metastasis, surgical margin status, and immunohistochemistry (IHC) staining results were obtained from patients' records. The tumors were classified into IHC-based molecular subtypes according to the St. Gallen Consensus Conference in 2013. A four-tiered scoring system was used based on ALDH1 staining percentage in tumor cells. The tumor was determined as positive if the score was 2 or higher. Clinical, histopathological findings, and ALDH1 staining results were correlated. Twenty-five cases (23.8%) were ALDH1 positive. The ALDH1 positive group compared to the negative group was found to be associated with ER negativity (p = 0.044), but there was no correlation with other clinical and histopathological findings. ALDH1-positive IDCs may be less sensitive to hormonal therapy and associated with aggressive behavior.}, } @article {pmid33111573, year = {2021}, author = {Santangelo, G and Raimo, S and Erro, R and Picillo, M and Amboni, M and Pellecchia, MT and Pivonello, C and Barone, P and Vitale, C}, title = {Vitamin D as a possible biomarker of mild cognitive impairment in parkinsonians.}, journal = {Aging & mental health}, volume = {25}, number = {11}, pages = {1998-2002}, doi = {10.1080/13607863.2020.1839860}, pmid = {33111573}, issn = {1364-6915}, mesh = {Biomarkers ; *Cognitive Dysfunction/epidemiology ; Cross-Sectional Studies ; Humans ; Longitudinal Studies ; Neuropsychological Tests ; Vitamin D ; }, abstract = {INTRODUCTION: Mild Cognitive Impairment in Parkinson's Disease (PD-MCI) is a transitional state between normal cognition and dementia. Cross-sectional studies revealed that low Vitamin D levels were associated with worse performance on cognitive tests in Parkinson's Disease. The present longitudinal study aimed to examine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at baseline and possible development of PD-MCI at 24 and 48 months.

MATERIALS AND METHODS: Sixty untreated, de novo PD patients underwent clinical and cognitive evaluations and measurement of serum 25(OH)D at baseline assessment (T0). After 24 (T1) and 48 months (T2), cognitive status (presence or absence of PD-MCI) of PD patients were re-evaluated.

RESULTS: Vitamin D insufficiency occurred in 93.3% at T0. At T1, significant differences among patients with PD-MCI at both baseline and follow-up, patients with PD-MCI at follow-up and patients who never developed PD-MCI were found on age, age at onset of PD, and education; no significant difference was found on vitamin D levels at T0. A binary logistic regression analysis showed that a lower level of 25(OH)D at T0 (B= -0.158, Wald= 5.280, p = 0.022, Exp (B)=0.854; CI 95%: 0.746-0.977) and lower education (B= -0.214, Wald= 3.859, p = 0.049, Exp (B)=0.807; CI 95%: 0652-1.000) were predictors of PD-MCI occurrence at T2.

DISCUSSION: Our results demonstrated that a lower level of 25(OH)D is conceivable as a biomarker of development of PD-MCI throughout the disease. Early diagnosis of Vitamin D insufficiency and its management might be useful to prevent cognitive decline in PD patients.}, } @article {pmid33108259, year = {2022}, author = {Mason, JR and Tenenbaum, G and Jaime, S and Roque, N and Maharaj, A and Figueroa, A}, title = {Arterial Stiffness and Cardiorespiratory Fitness Are Associated With Cognitive Function in Older Adults.}, journal = {Behavioral medicine (Washington, D.C.)}, volume = {48}, number = {1}, pages = {54-65}, pmid = {33108259}, issn = {0896-4289}, support = {T32 AG049676/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; *Cardiorespiratory Fitness ; Carotid Intima-Media Thickness ; Cognition ; Cross-Sectional Studies ; Humans ; Pulse Wave Analysis ; *Vascular Stiffness ; }, abstract = {Age-related cognitive impairment has been associated with arterial stiffening and decreased cardiorespiratory fitness. The aims of this cross-sectional study were to compare cognitive function domains and cardiovascular parameters in older adults (≥ 65 years old) with high and normal aortic stiffness (via carotid-femoral pulse wave velocity, cfPWV) and to explore relationships among cfPWV, carotid intima-media thickness, cardiorespiratory fitness, and cognitive function. Vascular and cognitive function were measured in older adults with either normal or high cfPWV. Cognitive function was measured via an intensive one-time neuropsychological battery, while cfPWV by applanation tonometry, carotid intima-media thickness and function (i.e., distensibility) by ultrasonography, and cardiorespiratory fitness (i.e., VO2peak) by a submaximal exercise test. Correlations among age, VO2peak, carotid intima-media thickness, cfPWV, and cognitive function were performed along with a series of multivariate analyses of variance. Compared with NAS, participants with HAS had greater aortic, carotid, and brachial blood pressures but similar cardiorespiratory fitness and carotid intima-media thickness and distensibility. Participants with NAS exhibited better neuropsychological performance in executive function and attention and overall cognitive function than those with HAS. When controlling for age, visual scanning and perception scores were correlated with cfPWV and VO2peak. Our findings suggest that certain cognitive domains for older adults are associated with their cardiorespiratory fitness and aortic stiffness.}, } @article {pmid33106505, year = {2020}, author = {Tsai, HT and Huang, CS and Tu, CC and Liu, CY and Huang, CJ and Ho, YS and Tu, SH and Tseng, LM and Huang, CC}, title = {Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18276}, pmid = {33106505}, issn = {2045-2322}, mesh = {Bayes Theorem ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Calcinosis/*diagnosis/genetics ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Taiwan ; Exome Sequencing ; }, abstract = {Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ[2]-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.}, } @article {pmid33103460, year = {2020}, author = {Srour, MK and Amersi, F and Mirocha, J and Giuliano, AE and Chung, A}, title = {Male Breast Cancer: 13-Year Single Institution Experience.}, journal = {The American surgeon}, volume = {86}, number = {10}, pages = {1345-1350}, doi = {10.1177/0003134820964444}, pmid = {33103460}, issn = {1555-9823}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Humans ; Lymphatic Metastasis ; Male ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Survival Rate ; }, abstract = {Due to the low incidence of male breast cancer (BC), there are few studies evaluating outcomes. We evaluated the clinicopathologic features and outcomes of male BC. Male patients with BC from January 2006 to December 2018 were identified. Of 49 patients, mean age was 64 (range 33-94) years. Of the 27 (55.1%) patients who had genetic testing, 9 (33.3%) had a Breast Cancer gene (BRCA) 1 or 2 mutation. The majority of patients had a mastectomy (n = 43/49, 87.8%) and had invasive ductal carcinoma (n = 47/49, 95.9%). 20 patients (n = 20/43, 46.5%) had positive lymph nodes. 41 (n = 41/47, 87.2%) patients had estrogen receptor positive disease. The majority of patients were pathologic stage 2 (n = 21/46, 45.7%), followed by stage 1 (n = 15/46, 32.6%), stage 3 (n = 6/46, 13.0%), and stage 4 (n = 4/46, 8.7%). Eight patients had the 21-gene recurrence score performed. Of patients with stage 1-3 BC, 10 (n = 10/43, 23.3%) patients had recurrence. With median follow-up of 4.1 (range .6-10.6) years, 5-year overall survival was 82.9% and 5-year disease-free survival was 65.9%. In conclusion, our cohort of patients with male BC had a high incidence of BRCA mutations and most commonly had high-grade estrogen positive stage 2 tumors. Breast conserving surgery was utilized in 4% of patients and genomic testing utilized in 55% of patients.}, } @article {pmid33103343, year = {2020}, author = {Milder, MTW and Alber, M and Söhn, M and Hoogeman, MS}, title = {Commissioning and clinical implementation of the first commercial independent Monte Carlo 3D dose calculation to replace CyberKnife M6™ patient-specific QA measurements.}, journal = {Journal of applied clinical medical physics}, volume = {21}, number = {11}, pages = {304-311}, pmid = {33103343}, issn = {1526-9914}, mesh = {Humans ; Monte Carlo Method ; Phantoms, Imaging ; Radiotherapy Dosage ; *Radiotherapy Planning, Computer-Assisted ; *Radiotherapy, Intensity-Modulated ; }, abstract = {PURPOSE: To report on the commissioning and clinical validation of the first commercially available independent Monte Carlo (MC) three-dimensional (3D) dose calculation for CyberKnife robotic radiosurgery system® (Accuray, Sunnyvale, CA).

METHODS: The independent dose calculation (IDC) by SciMoCa® (Scientific RT, Munich, Germany) was validated based on water measurements of output factors and dose profiles (unshielded diode, field-size dependent corrections). A set of 84 patient-specific quality assurance (QA) measurements for multi-leaf collimator (MLC) plans, using an Octavius two-dimensional SRS1000 array (PTW, Freiburg, Germany), was compared to results of respective calculations. Statistical process control (SPC) was used to detect plans outside action levels.

RESULTS: Of all output factors for the three collimator systems of the CyberKnife, 99% agreed within 2% and 81% within 1%, with a maximum deviation of 3.2% for a 5-mm fixed cone. The profiles were compared using a one-dimensional gamma evaluation with 2% dose difference and 0.5 mm distance-to-agreement (Γ(2,0.5)). The off-centre ratios showed an average pass rate >99% (92-100%). The agreement of the depth dose profiles depended on field size, with lowest pass rates for the smallest MLC field sizes. The average depth dose pass rate was 88% (35-99%). The IDCs showed a Γ(2,1) pass rate of 98%. Statistical process control detected six plans outside tolerance levels in the measurements, all of which could be attributed the measurement setup. Independent dose calculations showed problems in five plans, all due to differences in the algorithm between TPS and IDC. Based on these results changes were made in the class solution for treatment plans.

CONCLUSION: The first commercially available MC 3D dose IDC was successfully commissioned and validated for the CyberKnife and replaced all routine patient-specific QA measurements in our clinic.}, } @article {pmid33102390, year = {2020}, author = {Haroon, UM and O'Grady-Coyne, S and Davis, NF and Gullmann, C and Forde, JC and Smyth, GP and Power, RE and Cheema, IA and McLornan, L}, title = {Intraductal carcinoma of the prostate in an Irish prostate cancer patient cohort-an aggressive pathology and a strong familial link.}, journal = {Prostate international}, volume = {8}, number = {3}, pages = {107-111}, pmid = {33102390}, issn = {2287-8882}, abstract = {BACKGROUND: The prevalence of intraductal carcinoma of the prostate (IDC-P) is poorly studied in the Irish population. This study investigated the incidence and clinicopathologic characteristics of IDC-P in an Irish prostate cancer (PCa) patient cohort. The study also discusses the rationale for genetic counseling and screening in Irish patients with familial risk factors for IDC-P.

MATERIALS AND METHODS: This study investigated patients diagnosed with IDC-P on prostate biopsy from 2012 to 2016. Primary outcome measurements were incidence, management, and clinical outcomes after follow-up in patients with IDC-P. The secondary outcome measurement was to identify a familial link for IDC-P.

RESULTS: A total of 1,143 patients were diagnosed with PCa on needle biopsy, of which 30 (2.3%) had concomitant IDC-P. Mean age and prostate-specific antigen at diagnosis were 68.6 ± 10.5 years (range 53-85 years) and 9.15 ± 8.65 ng/mL (range 2.1-166 ng/mL), respectively. In total, 17 of 30 patients (57%) were diagnosed with concomitant high-grade (i.e., ≥Gleason score 8) PCa. Eight patients (27%) were treated with radical prostatectomy; of which five had biochemical recurrence (BCR) after 10.55 ± 25.9 months. Eleven patients (37%) received radical radiotherapy; of which one had BCR after 36 months. Eleven patients (37%) presented with advanced PCa and were managed with androgen deprivation therapy ± chemotherapy. A family history for PCa in first-degree relatives was found in eight patients (27%).

CONCLUSIONS: IDC-P is associated with more aggressive clinicopathologic features and an increased risk of BCR after treatment. In Ireland, clinical guidelines and a genetic screening pathway are required to provide early detection and appropriate multimodal management of patients with IDC-P.}, } @article {pmid33097605, year = {2021}, author = {Kurley, SJ and Tischler, V and Bierie, B and Novitskiy, SV and Noske, A and Varga, Z and Zürrer-Härdi, U and Brandt, S and Carnahan, RH and Cook, RS and Muller, WJ and Richmond, A and Reynolds, AB}, title = {A requirement for p120-catenin in the metastasis of invasive ductal breast cancer.}, journal = {Journal of cell science}, volume = {134}, number = {6}, pages = {}, pmid = {33097605}, issn = {1477-9137}, support = {R01 CA200681/CA/NCI NIH HHS/United States ; IK6 BX005225/BX/BLRD VA/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 CA055724/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; P30 HD015052/HD/NICHD NIH HHS/United States ; R01 CA243326/CA/NCI NIH HHS/United States ; R01 CA111947/CA/NCI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms/genetics ; Cadherins/genetics ; Catenins/genetics ; Cell Adhesion ; Female ; Humans ; Mice ; Tumor Microenvironment ; Delta Catenin ; }, abstract = {We report here the effects of targeted p120-catenin (encoded by CTNND1; hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal (mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor growth but caused significant pro-metastatic alterations in the tumor microenvironment, ultimately leading to a marked increase in the number and size of pulmonary metastases. Surprisingly, although early effects of p120-ablation included decreased cell-cell adhesion and increased invasiveness, cells lacking p120 were almost entirely unable to colonized distant metastatic sites in vivo The relevance of this observation to human IDC was established by analysis of a large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation in primary IDC predicted worse overall survival. However, as in the mice, distant metastases were almost invariably p120 positive, even in matched cases where the primary tumors were p120 negative. Collectively, our results demonstrate a strong positive role for p120 (and presumably E-cadherin) during metastatic colonization of distant sites. On the other hand, downregulation of p120 in the primary tumor enhanced metastatic dissemination indirectly via pro-metastatic conditioning of the tumor microenvironment.}, } @article {pmid33094579, year = {2020}, author = {Gill, SM and Hassan, A and Bashir, H}, title = {Unforeseen COVID-19 on Oncologic Bone Scan with SPECT/CT in a High Prevalence Area.}, journal = {Molecular imaging and radionuclide therapy}, volume = {29}, number = {3}, pages = {139-142}, pmid = {33094579}, issn = {2146-1414}, abstract = {A 65-year-old woman with known diabetes and hypertension underwent a technetium methylene diphosphonate (Tc-99m MDP) bone scan with single photon emission computed tomography/computed tomography (SPECT/CT) for shoulder pain. She was initially treated for breast cancer and later for hepatocellular carcinoma. SPECT/CT showed MDP nonavid and scattered pulmonary ground-glass opacities bilaterally along with rounded nodular densities. Another 56-year-old patient who was newly diagnosed with right breast invasive ductal carcinoma underwent a bone scan with SPECT/CT, which revealed bilateral pulmonary infiltrates. Both patients later tested positive for Coronavirus Disease-2019 (COVID-19). Therefore, nuclear physicians should be watchful of findings related to COVID-19 on SPECT/CT thorax as this is becoming the new normal.}, } @article {pmid33093167, year = {2020}, author = {Heaster, TM and Humayun, M and Yu, J and Beebe, DJ and Skala, MC}, title = {Autofluorescence Imaging of 3D Tumor-Macrophage Microscale Cultures Resolves Spatial and Temporal Dynamics of Macrophage Metabolism.}, journal = {Cancer research}, volume = {80}, number = {23}, pages = {5408-5423}, pmid = {33093167}, issn = {1538-7445}, support = {F31 CA247248/CA/NCI NIH HHS/United States ; R01 CA185747/CA/NCI NIH HHS/United States ; R01 CA205101/CA/NCI NIH HHS/United States ; R01 CA211082/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*pathology ; Cell Culture Techniques/instrumentation/*methods ; Cell Movement ; Coculture Techniques ; Female ; Flavin-Adenine Dinucleotide/metabolism ; Humans ; Imaging, Three-Dimensional ; Lab-On-A-Chip Devices ; Macrophages/*metabolism ; Mice ; NADP/metabolism ; Optical Imaging/*methods ; RAW 264.7 Cells ; Tumor Microenvironment ; }, abstract = {Macrophages within the tumor microenvironment (TME) exhibit a spectrum of protumor and antitumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to nondestructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours poststimulation for mouse macrophages (RAW264.7) stimulated with IFNγ or IL4 plus IL13 in 2D culture, confirming that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse polyoma-middle T virus or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor cocultures exhibited significantly different FAD mean lifetimes and greater migration than monocultures at 24, 48, and 72 hours postseeding. In cocultures with primary human cancer cells, actively migrating monocyte-derived macrophages had greater redox ratios [NAD(P)H/FAD intensity] compared with passively migrating monocytes at 24 and 48 hours postseeding, reflecting metabolic heterogeneity in this subpopulation of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor-immune cross-talk within the 3D TME. SIGNIFICANCE: Label-free metabolic imaging and microscale culture technologies enable monitoring of single-cell macrophage metabolism, migration, and function in the 3D tumor microenvironment.}, } @article {pmid33090732, year = {2020}, author = {Morigny, P and Zuber, J and Haid, M and Kaltenecker, D and Riols, F and Lima, JDC and Simoes, E and Otoch, JP and Schmidt, SF and Herzig, S and Adamski, J and Seelaender, M and Berriel Diaz, M and Rohm, M}, title = {High levels of modified ceramides are a defining feature of murine and human cancer cachexia.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {11}, number = {6}, pages = {1459-1475}, pmid = {33090732}, issn = {2190-6009}, support = {J 4224/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Cachexia/etiology ; *Ceramides/metabolism ; Humans ; Mice ; Muscular Atrophy ; *Neoplasms/complications ; Quality of Life ; }, abstract = {BACKGROUND: Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.

METHODS: Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc[Min/+] mutant mice), and plasma from weight stable and cachectic patients with gastrointestinal cancer, were analysed using the Lipidyzer™ platform. In total, 13 lipid classes and more than 1100 lipid species, including sphingolipids, neutral and polar glycerolipids, were covered by the analysis. Correlation analysis between specific lipid species and readouts of CCx were performed. Lipidomics data were confirmed by gene expression analysis of metabolic organs to analyse enzymes involved in sphingolipid synthesis and degradation.

RESULTS: A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.

CONCLUSIONS: High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.}, } @article {pmid33086236, year = {2021}, author = {Bishop, JA and Rooper, LM and Sangoi, AR and Gagan, J and Thompson, LDR and Inagaki, H}, title = {The Myoepithelial Cells of Salivary Intercalated Duct-type Intraductal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {4}, pages = {507-515}, doi = {10.1097/PAS.0000000000001605}, pmid = {33086236}, issn = {1532-0979}, mesh = {Aged ; Automation, Laboratory ; *Biomarkers, Tumor/analysis/genetics ; Calcium-Binding Proteins/*analysis ; *Carcinoma, Ductal/chemistry/genetics/pathology ; Female ; *Fluorescent Antibody Technique ; Gene Fusion ; Humans ; Image Interpretation, Computer-Assisted ; *In Situ Hybridization, Fluorescence ; Male ; Microfilament Proteins/*analysis ; Middle Aged ; Predictive Value of Tests ; Proto-Oncogene Proteins c-ret/*genetics ; *Salivary Gland Neoplasms/chemistry/genetics/pathology ; }, abstract = {Intraductal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) intercalated duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary duct carcinoma; and (3) mixed intercalated duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 intercalated duct-like IDCs with NCOA4-RET, and 1 mixed intercalated duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.}, } @article {pmid33084216, year = {2021}, author = {Arslan, E and Can Trabulus, D and Mermut, Ö and Şavlı, TC and Çermik, TF}, title = {Alternative volumetric PET pjmirometers for evaluation of breast cancer cases with 18F-FDG PET/CT imaging: Metabolic tumour volume and total lesion glycolysis.}, journal = {Journal of medical imaging and radiation oncology}, volume = {65}, number = {1}, pages = {38-45}, doi = {10.1111/1754-9485.13114}, pmid = {33084216}, issn = {1754-9485}, mesh = {*Breast Neoplasms/diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Glycolysis ; Humans ; Positron Emission Tomography Computed Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tumor Burden ; }, abstract = {INTRODUCTION: We aimed to investigate the prognostic and clinical values of two volumetric PET pjmirometers used in conjunction with SUVmax at different thresholds in invasive ductal carcinoma (IDC).

METHODS: A total of 139 metastatic IDC BC who underwent 18F-FDG PET/CT imaging were included to study. MTV and TLG (40%, 50%, 60% and 70%) used in conjunction with primary tumour SUVmax . Nodal involvement, distant metastasis, ER, PR, Ki-67 expression and survival data evaluated by comparing FDG PET pjmirometers.

RESULTS: Mean ± SD SUVmax of lesions (n = 139) was 13.97 ± 9.21. Primary tumour 18F-FDG uptake associated increased tumour diameter (>2 cm), high Ki-67 (>15%) and distant organ metastasis (DOM) (P = 0.015, 0.005 and 0.016, respectively). There was significant association between molecular subtypes and SUVmax (P = 0.002). High MTV associated with tumour diameter (MTV 40-70%), axillary lymph node (ALN) diameter (MTV 40-70%), and distant nodal metastasis (DNM) (MTV 50-70%). High TLG associated with tumour diameter (TLG 40-70%), high Ki-67 (TLG 40-70%), ALN metastasis (TLG 40%), ALN diameter (TLG 40-70%) and DNM (TLG 40-70%). Median survival found shorter in DOM patients (P = 0.030, Log Rank = 0.110).

CONCLUSION: We think evaluation of MTV and TLG at different thresholds in addition to SUVmax would enhance diagnostic and prognostic value of 18F-FDG PET/CT, and thus contribute to disease management.}, } @article {pmid33083532, year = {2020}, author = {Pareja, F and Ferrando, L and Lee, SSK and Beca, F and Selenica, P and Brown, DN and Farmanbar, A and Da Cruz Paula, A and Vahdatinia, M and Zhang, H and Zoppoli, G and Wen, HY and Brogi, E and Robson, ME and Razavi, P and Chandarlapaty, S and Weigelt, B and Reis-Filho, JS}, title = {The genomic landscape of metastatic histologic special types of invasive breast cancer.}, journal = {NPJ breast cancer}, volume = {6}, number = {}, pages = {53}, pmid = {33083532}, issn = {2374-4677}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {Histologic special types of breast cancer (BC) account for ~20% of BCs. Large sequencing studies of metastatic BC have focused on invasive ductal carcinomas of no special type (IDC-NSTs). We sought to define the repertoire of somatic genetic alterations of metastatic histologic special types of BC. We reanalyzed targeted capture sequencing data of 309 special types of BC, including metastatic and primary invasive lobular carcinomas (ILCs; n = 132 and n = 127, respectively), mixed mucinous (n = 5 metastatic and n = 14 primary), micropapillary (n = 12 metastatic and n = 8 primary), and metaplastic BCs (n = 6 metastatic and n = 5 primary), and compared metastatic histologic special types of BC to metastatic IDC-NSTs matched according to clinicopathologic characteristics and to primary special type BCs. The genomic profiles of metastatic and primary special types of BC were similar. Important differences, however, were noted: metastatic ILCs harbored a higher frequency of genetic alterations in TP53, ESR1, FAT1, RFWD2, and NF1 than primary ILCs, and in CDH1, PIK3CA, ERBB2, TBX3, NCOR1, and RFWD2 than metastatic IDC-NSTs. Metastatic ILCs displayed a higher mutational burden, and more frequently dominant APOBEC mutational signatures than primary ILCs and matched metastatic IDC-NSTs. ESR1 and NCOR mutations were frequently detected in metastatic mixed mucinous BCs, whereas PIK3CA and TP53 were the most frequently altered genes in metastatic micropapillary and metaplastic BCs, respectively. Taken together, primary and metastatic BCs histologic special types have remarkably similar repertoires of somatic genetic alterations. Metastatic ILCs more frequently harbor APOBEC mutational signatures than primary ILCs and metastatic IDC-NSTs.}, } @article {pmid33082758, year = {2020}, author = {Kitahara, M and Hozumi, Y and Takeuchi, N and Ichinohe, S and Machinaga, M and Iijima, T}, title = {Invasive Cancer Confined to the Nipple of the Conserved Breast: A Case Report.}, journal = {Case reports in oncology}, volume = {13}, number = {3}, pages = {1125-1130}, pmid = {33082758}, issn = {1662-6575}, abstract = {Invasive breast cancer deriving from the milk duct and lobule that develops in the nipple is extremely rare, except in Paget's disease and skin cancer. This is the second reported case of the development of invasive cancer confined to the nipple after breast-conserving surgery. A 69-year-old woman visited our department due to redness, swelling, and bloody discharge of the right nipple in the last month. A needle biopsy was suggestive of invasive ductal carcinoma; we performed a removal surgery of the right residual breast tissue and a second sentinel lymph node biopsy. She underwent these procedures 10 years previously as well. Thus, we diagnosed the present lesion as a local recurrence, but it was unknown whether the lesion was a true recurrence or second cancer, namely, metachronal ipsilateral breast cancer. The present case helps promote awareness that invasive cancer rarely develops in the nipple after conserving surgery. Patients should be encouraged to visit a medical facility if experiencing skin changes and swelling of the nipple. Additionally, breast cancer patients must be carefully selected for breast-conserving surgery; failure to do so may later result in nipple-specific local recurrence.}, } @article {pmid33078470, year = {2020}, author = {Vetter, C and Ashok, A and Perez, M and Musaad, S and Rahimi, G and Gohil, K and Higham, A}, title = {Impact of systematic cavity shave margins in breast-conserving surgery at a large community hospital with a low baseline re-excision rate.}, journal = {The breast journal}, volume = {26}, number = {10}, pages = {1960-1965}, doi = {10.1111/tbj.14057}, pmid = {33078470}, issn = {1524-4741}, mesh = {*Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating/surgery ; Female ; Hospitals, Community ; Humans ; Margins of Excision ; Mastectomy, Segmental ; Neoplasm, Residual ; Reoperation ; Retrospective Studies ; }, abstract = {Systematic cavity shave margins (CSM) can decrease rate of positive margins and re-excision beyond that of selective CSM. The objective of this study was to determine whether systematic CSM decreased re-excision rate in a population with a low baseline re-excision rate. We conducted a retrospective chart review of patients who underwent breast-conserving surgery (BCS) from November 2013 to November 2017. Primary end points were re-excision rate and margin status. Secondary end points were total volume of tissue excised, operative time, and concordance of core needle biopsy (CNB) pathology with final surgical pathology. The re-excision rates were 14.29% in the no shave margin group; 15.38% in the selective CSM; and 14.59% in the systematic CSM (P = .985). Odds of re-excision with ductal carcinoma in situ (DCIS) was 5.04 times greater than with invasive cancer (INV) and 1.94 times higher than with INV and DCIS. There was no significant difference in positive margins between groups (P = .362). Mean specimen volume was lowest in the systematic CSM group (64.6 cm[3]), compared to no CSM and selective CSM (94.6 cm[3] and 91.8 cm[3] , respectively). With inclusion of shave margin volumes, total volume removed was not significantly different between no shave margin group (94.6 cm[3]) and systematic CSM (89.7 cm[3]) (P = .949). For patients with invasive ductal carcinoma (IDC) alone on their initial biopsy pathology, 69% were discovered to also have DCIS upon final pathology. Re-excision rate and specimen volume between all groups were not statistically different. There was a higher re-excision rate when DCIS was present, especially when not identified on CNB. As systematic CSM is most impactful when DCIS is involved, it is important to establish its presence for proper surgical planning.}, } @article {pmid33078312, year = {2021}, author = {Özkurt, E and Wong, S and Rhei, E and Golshan, M and Brock, J and Barbie, TU}, title = {Omission of Surgical Axillary Lymph Node Staging in Patients with Tubular Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {28}, number = {5}, pages = {2589-2598}, pmid = {33078312}, issn = {1534-4681}, mesh = {Axilla/pathology ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Humans ; Lymph Nodes/pathology/surgery ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {BACKGROUND: With more effective screening and treatment strategies, there is debate over whether surgical axillary staging should be deescalated for patients with small favorable breast cancers, such as tubular carcinoma (TC).

PATIENTS AND METHODS: We identified patients with TC [defined as > 90% tubular tubules (angulated, not multilayered)] and known surgical axillary staging from our institutional database (2000-2018). Using the National Cancer Database (NCDB) (2004-2015), we identified patients with TC, ductal carcinoma in situ (DCIS), and pT1 estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). We determined the rates of lymph node (LN) metastases, and the 5- and 10-year overall survival (OS) for patients with LN-negative versus LN-positive disease using the Kaplan-Meier method and propensity match analysis.

RESULTS: In our institutional cohort, we identified 112 patients with T1 TC; only one (0.9%) patient had nodal involvement. In the NCDB cohort, we identified 6938 patients with T1 TC; 323 (4.7%) patients had axillary LN disease. The rate of axillary LN involvement for TC was comparable to that identified for patients with DCIS (4.2%), and much lower than that found for patients with grade I-III, T1, ER-positive IDC (20.5%), and patients with grade I, T1, ER-positive IDC (14.4%). There was no difference in 5-year (94.6% versus 95.4%, p = 0.67) and 10-year (83.9% versus 85.2%, p = 0.98) OS between TC patients with or without LN involvement. Kaplan-Meier survival curves even after propensity score matching suggest that tubular histology is independently associated with improved survival.

CONCLUSIONS: T1 TC is an excellent starting point for deescalation of surgical axillary staging.}, } @article {pmid33077335, year = {2021}, author = {Downes, MR and Xu, B and van der Kwast, TH}, title = {Cribriform architecture prostatic adenocarcinoma in needle biopsies is a strong independent predictor for lymph node metastases in radical prostatectomy.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {148}, number = {}, pages = {432-439}, doi = {10.1016/j.ejca.2020.09.016}, pmid = {33077335}, issn = {1879-0852}, mesh = {Adenocarcinoma/*pathology/surgery ; Aged ; Biopsy, Needle ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Follow-Up Studies ; Humans ; Lymphatic Metastasis/*diagnosis ; Male ; Middle Aged ; Neoplasm Grading ; *Nomograms ; Prostatectomy/*methods ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; }, abstract = {AIM: Lymph node metastases (pN1) at prostatectomy are infrequent but impact prognosis. Traditional prostate nomograms assess age, serum prostatic-specific antigen (PSA), clinical stage, and biopsy parameters to inform decisions on pelvic lymph node dissection. The impact of intraductal carcinoma (IDC) and cribriform pattern 4 (CC) on nodal metastases has yet to be explored.

METHODS: Five hundred forty three radical prostatectomy cases were reviewed for International Society of Urological Pathology (ISUP) grade, CC/IDC, T- and N-stage. Two hundred seventy five cases had matched biopsies with age, serum PSA, CC/IDC and ISUP grade recorded. The association of CC/IDC with pN1 in both prostatectomy and biopsy settings was assessed using Fisher's exact test, as well as univariable (UVA) and multivariable (MVA) logistic regression.

RESULTS: In 543 men in whom a prostatectomy was performed, a nodal dissection was also available in 340 (63%), and 37 (10.9%) of them had pN1 disease. ISUP grade, stage and CC/IDC were significantly associated with pN1 (p < 0.001). UVA regression showed grade (p < 0.001, odds ratio [OR]: 5.85), CC/IDC (p = 0.003, OR: 14.06) and T stage (p = 0.004, OR: 61.94) associated with pN1 as did MVA regression: grade (p = 0.010, OR: 2.81), CC/IDC (p = 0.015, OR: 5.12) and T stage (p = 0.016, OR: 30.38). In 275 patients with matched biopsies, a nodal dissection was performed in 197 (71.6%) and 20 (10.2%) patients had pN1 disease. On UVA regression, grade (p < 0.001, OR: 6.33), CC/IDC (p = 0.013, OR: 3.28), serum PSA (p = 0.001, OR: 1.08) and age (p = 0.047, OR: 1.07) were significant for pN1 at prostatectomy. All parameters including specifically grade (p = 0.007, OR: 5.35) and CC/IDC (p = 0.018, OR: 4.42) on biopsies predicted for pN1 by multivariate analysis.

CONCLUSION: CC/IDC in prostatectomy and biopsy significantly associates with pN1. Incorporation of CC/IDC status into preoperative nomograms may optimize patient selection for pelvic nodal dissection.}, } @article {pmid33077158, year = {2021}, author = {Lyons, D and Wahab, RA and Vijapura, C and Mahoney, MC}, title = {The nipple-areolar complex: comprehensive imaging review.}, journal = {Clinical radiology}, volume = {76}, number = {3}, pages = {172-184}, doi = {10.1016/j.crad.2020.09.013}, pmid = {33077158}, issn = {1365-229X}, mesh = {Breast Diseases/*diagnostic imaging/pathology ; Diagnostic Imaging/*methods ; Female ; Humans ; Nipples/*diagnostic imaging/pathology ; }, abstract = {The nipple-areolar complex can be affected by a variety of benign and malignant entities that can present with non-specific symptoms. Benign pathologies commonly affecting the nipple-areolar complex include nipple calcifications, nipple adenoma, abscess of Montgomery tubercles, ductal ectasia, periductal mastitis, and papilloma. Malignant pathologies that affect the nipple-areolar complex include Paget's disease of the breast, ductal carcinoma in-situ, and invasive ductal carcinoma. Clinical history and examination, imaging, and tissue sampling when appropriate are co-dependent factors that guide the assessment of nipple-areolar pathologies. This article provides a review of the normal anatomy, common anatomical variants, benign and malignant pathologies, and imaging techniques to guide the diagnostic assessment of the nipple-areolar complex.}, } @article {pmid33075624, year = {2021}, author = {Cherniak, AD and Mikulincer, M and Shaver, PR and Granqvist, P}, title = {Attachment theory and religion.}, journal = {Current opinion in psychology}, volume = {40}, number = {}, pages = {126-130}, doi = {10.1016/j.copsyc.2020.08.020}, pmid = {33075624}, issn = {2352-2518}, mesh = {Cross-Sectional Studies ; Humans ; Mental Health ; *Object Attachment ; Religion ; *Religion and Psychology ; }, abstract = {Attachment theory deals with the development and dynamics of interpersonal affectional bonds. It also provides a framework for understanding individuals' relationship with God, which is central to religion. We review basic concepts of attachment theory and survey research that has examined religion both in terms of normative attachment processes and individual differences in attachment. We cite evidence from cross-sectional, experimental, and longitudinal studies showing that many religious individuals experience God as a source of resilience (e.g. a safe haven and secure base). We also summarize proposed attachment-related developmental pathways to religion. Finally, we review research on religion and mental health undertaken from an attachment viewpoint and discuss future directions.}, } @article {pmid33075188, year = {2021}, author = {Zheng, YZ and Wang, XM and Fan, L and Shao, ZM}, title = {Breast Cancer-Specific Mortality in Small-Sized Tumor with Stage IV Breast Cancer: A Population-Based Study.}, journal = {The oncologist}, volume = {26}, number = {2}, pages = {e241-e250}, pmid = {33075188}, issn = {1549-490X}, mesh = {*Breast Neoplasms/mortality/pathology ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Small-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease.

MATERIALS AND METHODS: Data between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size.

RESULTS: We identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did.

CONCLUSION: Patients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients.

IMPLICATIONS FOR PRACTICE: This study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.}, } @article {pmid33074216, year = {2020}, author = {Tsuji, W}, title = {Metachronous bilateral ectopic breast carcinoma in the axilla: A case report and literature review.}, journal = {Breast disease}, volume = {39}, number = {3-4}, pages = {149-153}, doi = {10.3233/BD-200452}, pmid = {33074216}, issn = {1558-1551}, mesh = {Aged ; Axilla/*pathology ; Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast ; Choristoma/diagnosis/*pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Neoplasm Recurrence, Local/diagnosis/pathology/surgery ; }, abstract = {Bilateral ectopic axillary breast carcinoma is extremely rare. Here, we report the case of a 68-year-old woman who presented with a palpable mass in the right axilla. After ectopic breast carcinoma diagnosis, the patient underwent partial mastectomy and sentinel lymph node biopsy, followed by radiotherapy of the whole breast. Adjuvant endocrine therapy was administered for 5 years. Seven years after the first carcinoma diagnosis, the patient noticed a second tumor in the left axilla by herself at the age of 75 years. Core needle biopsy revealed second primary breast carcinoma of the axilla. She underwent partial mastectomy and sentinel lymph node biopsy followed by chemotherapy, radiotherapy, and endocrine therapy. No recurrence has been observed so far. Therefore, ectopic breast carcinoma should be treated as typical breast carcinoma.}, } @article {pmid33073677, year = {2020}, author = {Qi, P and Bai, QM and Yao, QL and Yang, WT and Zhou, XY}, title = {Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.}, journal = {Technology in cancer research & treatment}, volume = {19}, number = {}, pages = {1533033820960760}, pmid = {33073677}, issn = {1533-0338}, mesh = {Breast Neoplasms/*genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Transcriptome/*genetics ; }, abstract = {This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.}, } @article {pmid33073211, year = {2020}, author = {Dueñas, JP and Duque, CS and Cristancho, L and Méndez, M}, title = {Completion thyroidectomy: is timing important for transcervical and remote access approaches?.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {6}, number = {3}, pages = {165-170}, pmid = {33073211}, issn = {2589-1081}, abstract = {Completion thyroidectomy (CT) is employed after lobectomy when histopathological results mandates total removal of the gland as in case of well differentiated thyroid carcinoma (DTC). It is also employed as a second stage thyroid surgery when unfavorable events occur as in recurrent laryngeal nerve injury or when the surgeon finds out the case is beyond his/her expertise in an attempt to protect the contralateral side and allowing time for recovery or for an expert surgeon to help.}, } @article {pmid33072727, year = {2020}, author = {Gonjo, T and Narita, K and McCabe, C and Fernandes, RJ and Vilas-Boas, JP and Takagi, H and Sanders, R}, title = {Front Crawl Is More Efficient and Has Smaller Active Drag Than Backstroke Swimming: Kinematic and Kinetic Comparison Between the Two Techniques at the Same Swimming Speeds.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {570657}, pmid = {33072727}, issn = {2296-4185}, abstract = {The purpose of this study was to investigate differences in Froude efficiency (η F) and active drag (D A) between front crawl and backstroke at the same speed. η F was investigated by the three-dimensional (3D) motion analysis using 10 male swimmers. The swimmers performed 50 m swims at four swimming speeds in each technique, and their whole body motion during one upper-limb cycle was quantified by a 3D direct linear transformation algorithm with manually digitized video footage. Stroke length (SL), stroke frequency (SF), the index of coordination (IdC), η F , and the underwater body volume (UWV body) were obtained. D A was assessed by the measuring residual thrust method (MRT method) using a different group of swimmers (six males) due to a sufficient experience and familiarization required for the method. A two-way repeated-measures ANOVA (trials and techniques as the factors) and a paired t-test were used for the outcomes from the 3D motion analysis and the MRT method, respectively. Swimmers had 8.3% longer SL, 5.4% lower SF, 14.3% smaller IdC, and 30.8% higher η F in front crawl than backstroke in the 3D motion analysis (all p < 0.01), which suggest that front crawl is more efficient than backstroke. Backstroke had 25% larger D A at 1.2 m⋅s[-1] than front crawl (p < 0.01) in the MRT trial. A 4% difference in UWV body (p < 0.001) between the two techniques in the 3D motion analysis also indirectly showed that the pressure drag and friction drag were probably larger in backstroke than in front crawl. In conclusion, front crawl is more efficient and has a smaller D A than backstroke at the same swimming speed.}, } @article {pmid33063553, year = {2021}, author = {Ben-David, BM and Mentzel, M and Icht, M and Gilad, M and Dor, YI and Ben-David, S and Carl, M and Shakuf, V}, title = {Challenges and opportunities for telehealth assessment during COVID-19: iT-RES, adapting a remote version of the test for rating emotions in speech.}, journal = {International journal of audiology}, volume = {60}, number = {5}, pages = {319-321}, doi = {10.1080/14992027.2020.1833255}, pmid = {33063553}, issn = {1708-8186}, mesh = {Adult ; Attention ; Audiology/*methods ; Audiometry, Speech/*methods ; *COVID-19 ; Emotions ; Female ; Humans ; Male ; Quarantine ; SARS-CoV-2 ; Semantics ; Speech Perception ; Telemedicine/*methods ; *Voice Recognition ; Young Adult ; }, abstract = {OBJECTIVE: COVID-19 social isolation restrictions have accelerated the need to adapt clinical assessment tools to telemedicine. Remote adaptations are of special importance for populations at risk, e.g. older adults and individuals with chronic medical comorbidities. In response to this urgent clinical and scientific need, we describe a remote adaptation of the T-RES (Oron et al. 2020; IJA), designed to assess the complex processing of spoken emotions, based on identification and integration of the semantics and prosody of spoken sentences.

DESIGN: We present iT-RES, an online version of the speech-perception assessment tool, detailing the challenges considered and solution chosen when designing the telehealth tool. We show a preliminary validation of performance against the original lab-based T-RES.

STUDY SAMPLE: A between-participants design, within two groups of 78 young adults (T-RES, n = 39; iT-RES, n = 39).

RESULTS: i-TRES performance closely followed that of T-RES, with no group differences found in the main trends, identification of emotions, selective attention, and integration.

CONCLUSIONS: The design of iT-RES mapped the main challenges for remote auditory assessments, and solutions taken to address them. We hope that this will encourage further efforts for telehealth adaptations of clinical services, to meet the needs of special populations and avoid halting scientific research.}, } @article {pmid33062963, year = {2020}, author = {Groth, AK and Closs Ono, MC and Weihermann, V and Brasil Bastos, LZ and de Santana Rezende, TM and de Zorzi Dalke, DB and Borssuk Ferreira, CI}, title = {A Picture of Breast Reconstruction in a Public Oncology Hospital in Latin America: A Ten-Year Experience.}, journal = {European journal of breast health}, volume = {16}, number = {4}, pages = {244-249}, pmid = {33062963}, issn = {2587-0831}, abstract = {OBJECTIVE: Breast cancer is the most frequent malignant tumor among women worldwide, with the sole exception of non-melanoma skin cancer. Currently, one of the most common treatments in Brazil is modified radical mastectomy, which, although effective, leads to both physical and psychological complications. In this context, breast reconstruction seeks to restore the functional and psychosocial health of women. This study aims to investigate the characteristics of breast reconstructions after mastectomy by comparing immediate and delayed reconstructions.

MATERIALS AND METHODS: This is a retrospective observational study, which was performed by analyzing the electronic medical records of the Erasto Gaertner Hospital in Curitiba, Brazil, from between January 2007 and December 2017.

RESULTS: After applying exclusion criteria, we analyzed a total of 268 medical records from January 2010 to December 2017. The most frequent histological type was invasive ductal carcinoma. Patients treated after 2014 had a higher number of immediate reconstructions, and the most commonly used method was alloplastic reconstruction using expanders (66.5%). There was no significant difference in the frequency of immediate or late complications between patients who opted for immediate or delayed reconstructions. The most common immediate complication was surgical wound dehiscence, and the use of neoadjuvant chemotherapy was not associated with a higher rate of complications in immediate reconstructions.

CONCLUSION: The current preference is for immediate reconstructions with breast tissue expanders in combination with chemotherapy, which follows a trend in Brazil and worldwide that has been identified in the literature. Finally, the growth in immediate reconstructions with no associated increase in complications demonstrates the effectiveness of this practice.}, } @article {pmid33062353, year = {2020}, author = {Junak, M and Jecius, H and Erdrich, J}, title = {Cutaneous Metastasis in the Setting of Both Colon and Breast Primary Malignancies.}, journal = {Case reports in gastrointestinal medicine}, volume = {2020}, number = {}, pages = {8852459}, pmid = {33062353}, issn = {2090-6528}, abstract = {Colorectal cancer (CRC) is the third most diagnosed cancer in the United States, and many patients unfortunately have metastases at the time of their diagnosis. Cutaneous metastases of CRC have been reported in few journals and primarily as case reports due to their rarity. Here, we present the case of an 83-year-old woman with recently resected colon cancer, T4aN1bMx stage IIIB. She presented to our clinic for evaluation of a right midback mass, and a punch biopsy revealed dermal involvement by invasive, poorly differentiated carcinoma with epidermoid features. The mass was excised, and we ordered a PET scan in search of the primary tumor, which at that time was suspected to be of skin cancer origin. Surprisingly, this revealed a second malignancy triple-negative invasive ductal carcinoma of the left breast. The back mass stained positive for CK20, which was compatible with a metastasis from a colonic primary. After initially declining adjuvant therapy, the patient completed one cycle of capecitabine and oxaliplatin, which she tolerated poorly. She continued to further decline, developed widespread cutaneous metastases, and went home on hospice. Cutaneous lesions are an exceedingly rare site of metastasis for colon adenocarcinoma, and their clinical presentation can vary widely. It is important for providers to investigate any new skin lesion in a patient with a recent or remote history of malignancy, even if there were no sites of distant metastasis at initial diagnosis.}, } @article {pmid33059474, year = {2021}, author = {Chu, SY and Lee, J and Barlow, SM and Ben-David, B and Lim, KX and Foong, JH}, title = {Oral-diadochokinetic rates among healthy Malaysian-Mandarin speakers: A cross linguistic comparison.}, journal = {International journal of speech-language pathology}, volume = {23}, number = {4}, pages = {419-429}, doi = {10.1080/17549507.2020.1808701}, pmid = {33059474}, issn = {1754-9515}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging ; Female ; Humans ; *Language ; *Linguistics ; Male ; Middle Aged ; Young Adult ; }, abstract = {PURPOSE: This study examined the effects of non-word versus real word, age, and gender on oral-DDK rates among healthy Malaysian-Mandarin speakers. Comparison between non-word of Malaysian-Mandarin and Hebrew speakers was examined.

METHOD: One-hundred and seventeen speakers (18-83 years old, 46% men) were audio-recorded while performing non-word (repetition of "pataka") and real-word oral-DDK tasks ("butter cake" and " ([p[h]a4t[h]a1k[h]an4])"). The number of syllables produced in 8 seconds was counted from the audio recording to derive the oral-DDK rates. A MANOVA was conducted to compare the rates between age groups (young = 18-40 years, n = 56; middle = 41-60 years, n = 39; older = 61-83 years, n = 22) and gender. In a second analysis, "pataka" results were compared between this study and previous findings with Hebrew speakers.

RESULT: No gender effects were found. However, rates significantly decreased with age (p < 0.001). Repetition of real words was faster than that of non-words - English words (5.55 ± 1.19 syllables/s) > non-words (5.29 ± 1.23) > Mandarin words (4.91 ± 1.13). Malaysian-Mandarin speakers performed slower than Hebrew speakers on "pataka" task.

CONCLUSION: Aging has a large impact on oromotor functions, indicating that speech-language pathologists should consider using age-adjusted norms.}, } @article {pmid33053889, year = {2020}, author = {Sela, Y and Santamaria, L and Amichai-Hamburge, Y and Leong, V}, title = {Towards a Personalized Multi-Domain Digital Neurophenotyping Model for the Detection and Treatment of Mood Trajectories.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {20}, pages = {}, pmid = {33053889}, issn = {1424-8220}, support = {ES/N006461/1//Economic and Social Research Council/ ; M4081585.SS0//Nanyang Technological University/ ; M4012105.SS0//Ministry of Education - Singapore/ ; }, mesh = {*Affect ; *Electroencephalography ; Humans ; Mental Health ; *Mobile Applications ; Technology ; }, abstract = {The commercial availability of many real-life smart sensors, wearables, and mobile apps provides a valuable source of information about a wide range of human behavioral, physiological, and social markers that can be used to infer the user's mental state and mood. However, there are currently no commercial digital products that integrate these psychosocial metrics with the real-time measurement of neural activity. In particular, electroencephalography (EEG) is a well-validated and highly sensitive neuroimaging method that yields robust markers of mood and affective processing, and has been widely used in mental health research for decades. The integration of wearable neuro-sensors into existing multimodal sensor arrays could hold great promise for deep digital neurophenotyping in the detection and personalized treatment of mood disorders. In this paper, we propose a multi-domain digital neurophenotyping model based on the socioecological model of health. The proposed model presents a holistic approach to digital mental health, leveraging recent neuroscientific advances, and could deliver highly personalized diagnoses and treatments. The technological and ethical challenges of this model are discussed.}, } @article {pmid33049657, year = {2020}, author = {Zhang, J and Lu, CY and Qin, L and Chen, HM and Wu, SY}, title = {Breast-conserving surgery with or without irradiation in women with invasive ductal carcinoma of the breast receiving preoperative systemic therapy: A cohort study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {139-147}, pmid = {33049657}, issn = {1532-3080}, mesh = {Adult ; Antineoplastic Protocols ; Breast/pathology ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Chemotherapy, Adjuvant/methods/*mortality ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods/*mortality ; Middle Aged ; Neoplasm Recurrence, Local/etiology/pathology ; Neoplasm Staging ; Neoplasm, Residual ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant/methods/*mortality ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival.

PATIENTS AND METHODS: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs).

RESULTS: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2-4) or nodal (ypN2-3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03-0.81), 0.32 (0.16-0.64), 0.43 (0.23-0.79), 0.23 (0.13-0.42), 0.52 (0.20-1.33), and 0.34 (0.13-0.87) in the ypT0, ypT1, ypT2-4, ypN0, ypN1, and ypN2-3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00-4.07), 0.46 (0.26-0.83), 0.18 (0.06-0.51), 0.28 (0.06-1.34), 0.25 (0.10-0.63), 0.47 (0.23-0.88), and 0.32 in the cT0-1, cT2, cT3, cT4, cN0, cN1, and cN2-3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST.

CONCLUSION: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.}, } @article {pmid33047861, year = {2020}, author = {Singh, K and Sung, CJ and Quddus, MR}, title = {Descriptive study comparing outcomes of classic and nonclassic lobular carcinoma in situ (florid and pleomorphic) initially diagnosed on core needle biopsy.}, journal = {The breast journal}, volume = {26}, number = {12}, pages = {2350-2356}, doi = {10.1111/tbj.14085}, pmid = {33047861}, issn = {1524-4741}, mesh = {Biopsy, Large-Core Needle ; *Breast Carcinoma In Situ/surgery ; *Breast Neoplasms ; *Carcinoma in Situ/surgery ; *Carcinoma, Lobular ; Female ; Humans ; Neoplasm Recurrence, Local ; }, abstract = {The lobular carcinoma in situ (LCIS) subtypes include classic (CLCIS), pleomorphic (PLCIS), and florid LCIS (FLCIS). The CLCIS is considered a breast cancer risk factor, but clinical significance and natural history of other LCIS subtypes are unclear. The outcome data on PLCIS and FLCIS is limited. The aim of current study is to compare excision and follow-up findings of CLCIS and nonclassic LCIS (NCLCIS). The breast needle biopsies (NBs) with LCIS during 01/2007-12/2017 were identified. The imaging, clinical findings, and outcome were compared between CLCIS and NCLCIS. A total of 36 NBs from 32 patients with NCLCIS (14 PLCIS & 22 FLCIS) and 73 NBs from 68 patients with CLCIS were identified. The NCLCIS patients were older (57 vs 52 years; P = .02) and presented more often with calcifications (78% vs 44%; P = .01). Seven (19%) PLCIS were initially diagnosed as ductal carcinoma in situ (DCIS). The microscopic invasion was frequent with NCLCIS (25%). No invasion was identified in NBs with CLCIS. A separate concurrent NBs with a carcinoma (29% vs 6%; P = .018) or ductal atypia (12% vs 3%; P = .1) was more frequent with CLCIS. The upgrade rate (invasion or DCIS) was higher with NCLCIS (25% vs 4%). Four NCLCIS developed ipsilateral recurrences: 2 NCLCIS, 1 IDC, and 1 ILC (50; 10-96 months). No breast event was reported in 24 pure CLCIS (60; 8-144 months). Invasive carcinoma with NCLCIS, unlike CLCIS, is always lobular type. Recurrences following NCLCIS are ipsilateral lobular tumors. NCLCIS subtypes are nonobligate precursors to invasive lobular carcinoma.}, } @article {pmid33047834, year = {2021}, author = {Nishimoto, A and Kuwahara, H and Ohashi, R and Ansai, SI}, title = {Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.}, journal = {Journal of cutaneous pathology}, volume = {48}, number = {1}, pages = {165-170}, doi = {10.1111/cup.13896}, pmid = {33047834}, issn = {1600-0560}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Mucins ; Neoplasms, Multiple Primary/*pathology ; Skin Neoplasms/*pathology ; Sweat Gland Neoplasms/*pathology ; Uterine Neoplasms/pathology ; }, abstract = {Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.}, } @article {pmid33039708, year = {2020}, author = {Bitencourt, AGV and Gibbs, P and Rossi Saccarelli, C and Daimiel, I and Lo Gullo, R and Fox, MJ and Thakur, S and Pinker, K and Morris, EA and Morrow, M and Jochelson, MS}, title = {MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103042}, pmid = {33039708}, issn = {2352-3964}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Biomarkers ; Breast Neoplasms/*diagnostic imaging/*genetics/therapy ; Female ; *Gene Expression ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; *Machine Learning ; *Magnetic Resonance Imaging/methods ; Middle Aged ; Neoadjuvant Therapy ; ROC Curve ; Receptor, ErbB-2/*genetics/metabolism ; Young Adult ; }, abstract = {BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC).

METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20).

FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test).

INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients.

FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.}, } @article {pmid33034530, year = {2021}, author = {}, title = {Corrigendum to Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data.}, journal = {Journal of medical screening}, volume = {28}, number = {3}, pages = {NP1}, doi = {10.1177/0969141320966461}, pmid = {33034530}, issn = {1475-5793}, } @article {pmid33033351, year = {2020}, author = {Shin, J and Park, S and Kim, E}, title = {Anisotropic transport induced by DC electrical current bias near the critical current.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {16841}, pmid = {33033351}, issn = {2045-2322}, abstract = {We investigated the transport characteristics of a square shape superconducting Ta thin film under DC electrical current bias along the diagonal direction. The resistance parallel (R∥) and perpendicular (R⊥) to the DC current, IDC, is measured with various magnetic fields. R∥ and R⊥ show contrasting dependence on IDC. First, the critical current of R∥ is smaller than that of R⊥. Second, R⊥ shows an unexpected reduction at current bias where R∥ shows a rapid increase near the transition from a flux flow state to a normal state. The intriguing anisotropic transport characteristics can be understood by the inhomogeneous current density profile over the square sample. Diagonal DC current induces an anisotropic current density profile where the current density is high near the biasing electrode and low at the center of the sample. Accordingly, the electrical transport in the perpendicular direction could remain less affected even near the critical current of R∥, which leads to the higher critical current in R⊥. Complicated conduction profile may also allow the anomalous reduction in the R⊥ before finally shifting to the normal state.}, } @article {pmid33029926, year = {2020}, author = {Gao, Y and Wang, C and Chi, W and Liu, X}, title = {Molecular Origins of Heteroatom Engineering on the Emission Wavelength Tuning, Quantum Yield Variations and Fluorogenicity of NBD-like SCOTfluors.}, journal = {Chemistry, an Asian journal}, volume = {15}, number = {23}, pages = {4082-4086}, doi = {10.1002/asia.202000966}, pmid = {33029926}, issn = {1861-471X}, support = {51902124//National Natural Science Foundation of China/ ; //SUTD/ ; T1SRCI17126//SUTD-MIT International Design Centre (IDC)/ ; IDG31800104//SUTD-MIT International Design Centre (IDC)/ ; }, abstract = {Molecular engineering of fluorophore scaffolds, especially heteroatom replacement, is a promising method to yield novel fluorophores with tailored properties for various applications. Yet, molecular origins of the distinct fluorescent properties in newly developed SCOTfluors, i. e., varied emission wavelengths, distinct quantum yields, and fluorogenicity, remain elusive. Such understanding, however, is critical for the rational molecular engineering of high-performance fluorophores. Herein, we employed quantum chemical calculations to understand the structure-property relationships of nitrobenzoxadiazole (NBD)-like SCOTfluors. Our findings are important not only for the rational deployment of SCOTfluors, but also for the effective modifications of other fluorophore scaffolds, for satisfying the increasingly diversified requirements of bioimaging and biosensing applications.}, } @article {pmid33027710, year = {2021}, author = {Thongpiya, J and Sa-Nguanraksa, D and Samarnthai, N and Sarasombath, PT}, title = {Filariasis of the breast caused by Brugia pahangi: A concomitant finding with invasive ductal carcinoma.}, journal = {Parasitology international}, volume = {80}, number = {}, pages = {102203}, pmid = {33027710}, issn = {1873-0329}, mesh = {Animals ; Breast Diseases/*diagnosis/parasitology ; Breast Neoplasms/*pathology ; Brugia pahangi/classification/*isolation & purification ; Carcinoma, Ductal, Breast/*pathology ; DNA, Ribosomal Spacer/analysis ; Female ; Filariasis/*diagnosis/parasitology ; Humans ; Middle Aged ; RNA, Helminth/analysis ; RNA, Ribosomal/analysis ; Thailand ; }, abstract = {Extralymphatic filariasis is an uncommon phenomenon that can be caused by several lymphatic filarial species, including zoonotic filaria of animal origins. In this study, we report a case of a 64-year-old Thai woman who presented with a lump in her left breast that was diagnosed with invasive ductal carcinoma. At the same time, a small nodule was found in her right breast, via imaging study, without any abnormal symptoms. A core needle biopsy of the right breast nodule revealed a filarial-like nematode compatible with the adult stage of Brugia sp. A molecular identification of the nematode partial mt 12rRNA gene and ITS1 suggested the causative species as closely related to Brugia pahangi, a zoonotic lymphatic filaria of animals such as cats and dogs. The sequence of the partial mt 12rRNA and ITS1 gene in this patient was 94% and 99% identical to the previously reported sequence of mt 12rRNA and ITS1 genes of B. pahangi. The sequence of ITS1 gene is 99% similar to B. pahangi microfilaria from infected dogs in Bangkok, which was highly suspected of having a zoonotic origin. As far as we know, this is the first case report of B. pahangi filariasis presented with a breast mass concomitantly found in a patient with invasive ductal carcinoma. This raised serious concern regarding the zoonotic transmission of filariasis from natural animal reservoirs.}, } @article {pmid33027673, year = {2020}, author = {Bartelt, A and Weber, C}, title = {Mitochondrial Ejection for Cardiac Protection: The Macrophage Connection.}, journal = {Cell metabolism}, volume = {32}, number = {4}, pages = {512-513}, doi = {10.1016/j.cmet.2020.09.014}, pmid = {33027673}, issn = {1932-7420}, mesh = {*Heart Failure/metabolism ; Homeostasis ; Humans ; Macrophages ; *Mitochondria ; Myocytes, Cardiac/metabolism ; }, abstract = {Mitochondrial dysfunction is a hallmark of heart disease. Nicolás-Ávila et al. (2020) now find that cardiomyocytes eject dysfunctional mitochondria in exopher vesicles, which require elimination by specialized heart-resident macrophages, altogether supporting proper heart function.}, } @article {pmid33027370, year = {2020}, author = {Gewehr, DM and Salgueiro, GR and Noronha, L and Kubrusly, FB and Kubrusly, LF and Coltro, GA and Preto, PC and Bertoldi, AS and Vieira, HI}, title = {Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {3}, pages = {480-490}, pmid = {33027370}, issn = {1678-4170}, mesh = {Animals ; Humans ; *Hypertension, Pulmonary/chemically induced ; Hypertrophy, Right Ventricular/chemically induced ; Male ; Monocrotaline/toxicity ; *Pulmonary Arterial Hypertension ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.

OBJECTIVE: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.

METHODS: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.

RESULTS: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).

CONCLUSION: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).}, } @article {pmid33024608, year = {2020}, author = {Matich, A and Sud, S and Buxi, TBS and Dogra, V}, title = {Idiopathic Granulomatous Mastitis and its Mimics on Magnetic Resonance Imaging: A Pictorial Review of Cases from India.}, journal = {Journal of clinical imaging science}, volume = {10}, number = {}, pages = {53}, pmid = {33024608}, issn = {2156-7514}, abstract = {OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast, which is benign but potentially morbid. Mammographic and sonographic findings have been well characterized, but magnetic resonance imaging (MRI) findings have been less thoroughly documented. The objective of this study was to demonstrate characteristic findings for IGM and its mimics via a retrospective review.

MATERIAL AND METHODS: Breast MRI examinations performed at Sir Ganga Ram Hospital in New Delhi, India between 2014 and 2019 were retrospectively reviewed to identify cases in which a pattern suggestive of granulomatous mastitis was seen. Cases of known malignancy were excluded. Any available breast pathology results were then obtained, and cases with presumptive or definitive diagnoses were compiled for analysis.

RESULTS: Overall, cases identified with characteristic imaging findings and confirmed diagnosis included seven cases of IGM, four cases of invasive ductal carcinoma, two cases of tuberculous mastitis, one case of non- tuberculous infectious mastitis, one case of foreign body mastitis, and one case of eosinophilc mastitis. One case of IGM with masses rather than of non-mass enhancement was also identified.

CONCLUSION: In our review, cases with clustered ring enhancement were found to have inflammatory, idiopathic, infectious and malignant etiologies. While, these etiologies can only be reliably differentiated on pathology, familiarity with the pattern and an awareness of the differential may lead to decreased morbidity due to delays in diagnosis.}, } @article {pmid33023170, year = {2020}, author = {Petre, AR and Craciunescu, R and Fratu, O}, title = {Design, Implementation and Simulation of a Fringing Field Capacitive Humidity Sensor.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {19}, pages = {}, pmid = {33023170}, issn = {1424-8220}, support = {51675/09.07.2019, SMIS code 125125//Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement/ ; 33PCCDI/2018//Ministry of Innovation and Research, UEFISCDI, MultiMonD2 within PNCDI III/ ; }, abstract = {The world population is growing in an accelerated way urging the need for a more efficient and sustainable agricultural industry. Initially developed for smart cities which face the same challenges caused by an increasing population, Internet of Things (IoT) technologies have evolved rapidly over the last few years and are now moving successfully to agriculture. Wireless Sensor Networks (WSNs) have been reported to be used in the agri-food sector and could answer the call for a more optimized agricultural management. This paper investigates a PCB-made interdigited capacitive (IDC) soil humidity sensor as a low-price alternative to the existing ones on the market. An in-depth comparative study is performed on 30 design variations, part of them also manufactured for further investigations. By measurements and simulations, the influence of the aspect ratio and dielectric thickness on the sensitivity and capacitance of the sensor are studied. In the end, a Humidity and Temperature Measurement Wireless Equipment (HTMWE) for IoT agriculture applications is implemented with this type of sensor.}, } @article {pmid33016589, year = {2019}, author = {Merry, R and Butenhoff, K and Campbell, BW and Michno, JM and Wang, D and Orf, JH and Lorenz, AJ and Stupar, RM}, title = {Identification and Fine-Mapping of a Soybean Quantitative Trait Locus on Chromosome 5 Conferring Tolerance to Iron Deficiency Chlorosis.}, journal = {The plant genome}, volume = {12}, number = {3}, pages = {1-13}, doi = {10.3835/plantgenome2019.01.0007}, pmid = {33016589}, issn = {1940-3372}, mesh = {Genome-Wide Association Study ; *Iron Deficiencies ; *Plant Diseases ; Quantitative Trait Loci ; Soybeans/*genetics ; }, abstract = {CORE IDEAS: 'Fiskeby III' harbors a combination of abiotic stress traits, including iron deficiency chlorosis (IDC) tolerance. An IDC quantitative trait locus on chromosome Gm05 was identified in genome-wide association studies and biparental populations. Fine-mapping resolved a 137-kb interval containing strong candidate genes. Iron deficiency chlorosis (IDC) is an important nutrient stress for soybean [Glycine max (L.) Merr.] grown in high-pH soils. Despite numerous agronomic attempts to alleviate IDC, genetic tolerance remains the most effective preventative measure against symptoms. In this study, two association mapping populations and a biparental mapping population were used for genetic mapping of IDC tolerance. Quantitative trait loci (QTLs) were identified on chromosomes Gm03, Gm05, and Gm06. Heterogenous inbred families were developed to fine-map the Gm05 QTL, which was uniquely supported in all three mapping populations. Fine-mapping resulted in a QTL with an interval size of 137 kb on the end of the short arm of Gm05, which produced up to a 1.5-point reduction in IDC severity on a 1 to 9 scale in near isogenic lines.}, } @article {pmid33014784, year = {2020}, author = {Ding, S and Zong, Y and Lin, C and Andriani, L and Chen, W and Liu, D and Chen, W and Li, Y and Shen, K and Wu, J and Zhu, L}, title = {Validation of the Prognostic Stage of American Joint Committee on Cancer Eighth Edition Staging Manual in Invasive Lobular Carcinoma Compared to Invasive Ductal Carcinoma and Proposal of a Novel Score System.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1471}, pmid = {33014784}, issn = {2234-943X}, abstract = {Purpose: The objective of this study was to evaluate the American Joint Committee on Cancer (AJCC) pathological prognostic stage among patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) and to propose a modified score system if necessary. Methods: Women diagnosed with IDC and ILC during 2010-2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively identified. Disease-specific survival (DSS) and overall survival (OS) were estimated by Kaplan-Meier method. Predictive performances of different staging systems were evaluated based on Harrell concordance index (C-index) and Akaike Information Criterion (AIC). Multivariate Cox models were conducted to build preferable score systems. Results: A total of 184,541 female patients were included in the final analyses, with a median follow-up of 30.0 months. In IDC cohort, the pathological prognostic stage (C-index, 0.8281; AIC, 110274.5) was superior to the anatomic stage (C-index, 0.8125; AIC, 112537.0; P < 0.001 for C-index) in risk stratification with respect to DSS. In ILC cohort, the prognostic stage (C-index, 0.8281; AIC, 7124.423) didn't outperform the anatomic stage (C-index, 0.8324; AIC, 7144.818; P = 0.748 for C-index) with respect to DSS. Similar results were observed with respect to OS. The score system defined by anatomic stage plus grade plus estrogen receptor and progesterone receptor (AS+GEP) allows for better staging (C-index, 0.8085; AIC, 7178.448) for ILC patients. Conclusion: Compared with anatomic stage, the pathological prognostic stage provided more accurate stratification for patients with IDC, but not for patients with ILC. The AS+GEP score system may fit ILC tumors better.}, } @article {pmid33014597, year = {2020}, author = {Butola, A and Prasad, DK and Ahmad, A and Dubey, V and Qaiser, D and Srivastava, A and Senthilkumaran, P and Ahluwalia, BS and Mehta, DS}, title = {Deep learning architecture "LightOCT" for diagnostic decision support using optical coherence tomography images of biological samples.}, journal = {Biomedical optics express}, volume = {11}, number = {9}, pages = {5017-5031}, pmid = {33014597}, issn = {2156-7085}, abstract = {Optical coherence tomography (OCT) is being increasingly adopted as a label-free and non-invasive technique for biomedical applications such as cancer and ocular disease diagnosis. Diagnostic information for these tissues is manifest in textural and geometric features of the OCT images, which are used by human expertise to interpret and triage. However, it suffers delays due to the long process of the conventional diagnostic procedure and shortage of human expertise. Here, a custom deep learning architecture, LightOCT, is proposed for the classification of OCT images into diagnostically relevant classes. LightOCT is a convolutional neural network with only two convolutional layers and a fully connected layer, but it is shown to provide excellent training and test results for diverse OCT image datasets. We show that LightOCT provides 98.9% accuracy in classifying 44 normal and 44 malignant (invasive ductal carcinoma) breast tissue volumetric OCT images. Also, >96% accuracy in classifying public datasets of ocular OCT images as normal, age-related macular degeneration and diabetic macular edema. Additionally, we show ∼96% test accuracy for classifying retinal images as belonging to choroidal neovascularization, diabetic macular edema, drusen, and normal samples on a large public dataset of more than 100,000 images. The performance of the architecture is compared with transfer learning based deep neural networks. Through this, we show that LightOCT can provide significant diagnostic support for a variety of OCT images with sufficient training and minimal hyper-parameter tuning. The trained LightOCT networks for the three-classification problem will be released online to support transfer learning on other datasets.}, } @article {pmid33011829, year = {2021}, author = {Sadeghalvad, M and Mohammadi-Motlagh, HR and Rezaei, N}, title = {Immune microenvironment in different molecular subtypes of ductal breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {185}, number = {2}, pages = {261-279}, pmid = {33011829}, issn = {1573-7217}, support = {41086//Tehran University of Medical Sciences/ ; }, mesh = {Biomarkers, Tumor ; *Breast Neoplasms/genetics/immunology ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; *Immunity, Cellular ; Prognosis ; *Tumor Microenvironment ; }, abstract = {PURPOSE: Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.

RESULTS: The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR[-] T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER[-] and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER[+] BC, although in other subtypes such as TN or HER2[+] are associated with a favorable prognosis.

CONCLUSION: Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.}, } @article {pmid33011180, year = {2020}, author = {Roberts, WC and Everett, BP and Won, VS and Kondapalli, N}, title = {Diagnostic Usefulness of Histological Examination of the Left Ventricular "Core" Excised to Insert a Left Ventricular Assist Device in Patients With Severe Heart Failure.}, journal = {The American journal of cardiology}, volume = {137}, number = {}, pages = {71-76}, doi = {10.1016/j.amjcard.2020.09.038}, pmid = {33011180}, issn = {1879-1913}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Female ; Heart Failure/*diagnosis/physiopathology/therapy ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Severity of Illness Index ; Stroke Volume/*physiology ; Ventricular Function, Left/*physiology ; Young Adult ; }, abstract = {The left ventricular assist device (LVAD) has proven to be beneficial for patients with severe heart failure poorly responsive to anti heart failure medicine. To examine both grossly and histologically the portion of left ventricular (LV) free wall excised ("the left ventricular core") to insert a LVAD in 337 patients with severe heart failure from a variety of causes. We collected together all photographs of LV "cores" and the histologic sections prepared from them and reexamined both. Despite the fact that these LV cores usually weighed >100 times the quantity of myocardium available to examine compared with that available by biotome inserted via a transvenous catheter, the number in which histologic study allowed an unequivocal diagnosis was limited. Examination of the clinical records usually was required to establish the definitive diagnosis. Although the presence of a scarred myocardial wall usually suggested ischemic cardiomyopathy (IC), the scarring may not have involved the LV apex resulting in a nonscarred portion of myocardium simulating idiopathic dilated cardiomyopathy (IDC). Moreover, about 10% of the patients with IDC have myocardial scars thus simulating IC. Involvement of the LV core by amyloid, sarcoid, myocarditis, and acute infarction, of course, allowed a specific anatomic diagnosis. Despite the presence of ample tissue to secure a definitive diagnosis, the combination of clinical input and morphologic assessment was required to arrive at a definite diagnosis in most patients.}, } @article {pmid33005404, year = {2020}, author = {Monzen, S and Tatara, Y and Mariya, Y and Chiba, M and Wojcik, A and Lundholm, L}, title = {HER2-positive breast cancer that resists therapeutic drugs and ionizing radiation releases sphingomyelin-based molecules to circulating blood serum.}, journal = {Molecular and clinical oncology}, volume = {13}, number = {6}, pages = {70}, pmid = {33005404}, issn = {2049-9450}, abstract = {Breast cancer is the second most common cancer in the world based on incidence, reaching more than 2 million new cases in 2018, while continuing to increase. Invasive ductal carcinoma is the most common type of this cancer, making up approximately 70-80% of all breast cancer diagnoses. In particular, the type of breast cancer overexpressing human epidermal growth factor receptor 2 (HER2) has potential of strong proliferation, migration and invasion and early treatment is necessary. The authors identified and studied a single patient displaying complete therapeutic resistance to monoclonal anti-HER2 antibody therapy, chemotherapy and radiotherapy. A patient who exhibited resistance to postoperative adjuvant therapy after mastectomy was selected from HER2-positive breast cancer, and this patient had the grade of T4bN2aM0, Stage IIIB. The patient samples, blood serum and cancer tissue, were analyzed by metabolome and immunostaining technique, respectively. The characteristics of peripheral blood serum and solid tumor were investigated, aiming to find new serum biomarker(s) using the metabolomics technique. A correlation between the appearance of HER2-positive cancer tissue and serum concentration of the sphingomyelin family was found. In addition, HER2-positive tumor tissue in both the primary and recurrent cancer express the sphingomyelinase. These results suggest that sphingomyelins from this cancer tissue leads to therapy resistance, induction of invasion and strong proliferation.}, } @article {pmid33005283, year = {2020}, author = {Paolini, B and Leddy, R and Irshad, A}, title = {Disappearing grouped breast calcifications: An ominous sign.}, journal = {Radiology case reports}, volume = {15}, number = {11}, pages = {2453-2458}, pmid = {33005283}, issn = {1930-0433}, abstract = {Spontaneous disappearing breast calcifications is a rarely-reported phenomenon and the relatively small number of studies that have been done mostly associated the resolution of benign-appearing breast calcifications with benign processes. We present a case of a postmenopausal woman who had spontaneously resolving grouped, coarse heterogenous calcifications in the setting a new soft tissue mass which was pathologically proven to be invasive ductal carcinoma. A handful of studies have shown the resolution of indeterminant calcifications to be associated with malignancy, and interestingly, all of these cases also demonstrated a new parenchymal abnormality which is akin to the present case. Overall, the majority of benign-appearing spontaneous resolving microcalcifications likely are related to benign processes; however, radiologists should be aware of the association of disappearing grouped, indeterminant calcifications with the resulting development of malignancy, especially in the presence of a nearby, newly-forming soft tissue mass.}, } @article {pmid32996352, year = {2021}, author = {Solan, M and Brunstein Klomek, A and Ankori, G and Bloch, A and Apter, A and Plishty, S}, title = {Impact of a New Parent Behavioral-Schema Training on Children with ADHD: A Pragmatic Control Trial.}, journal = {Journal of attention disorders}, volume = {25}, number = {14}, pages = {2048-2059}, doi = {10.1177/1087054720959711}, pmid = {32996352}, issn = {1557-1246}, mesh = {*Attention Deficit Disorder with Hyperactivity/therapy ; Behavior Therapy ; Child ; Comorbidity ; Humans ; Parents ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: To examine whether adding schema therapy strategies to the conventional parent behavioral program prevents symptom relapse in children with attention deficit hyperactivity disorder (ADHD).

METHOD: The intervention was designed as an adaptive pragmatic control trial. The parent behavioral training and schema-enhanced parent behavior therapy (SPBT) protocols were delivered to the control group (40 parents of 23 children) and experimental group (97 parents of 54 children), respectively. Participants were assessed at baseline, mid-treatment, and termination. Parents and teachers indicated the severity of ADHD and comorbid symptoms through their responses to standardized questionnaires designed for this purpose.

RESULTS: A nested growth curve analysis demonstrated that participants in the schema-enhanced intervention group had a lower risk of symptom relapse than the control group.

CONCLUSION: Participation in the SPBT program significantly reduced relapse rates by the end of the intervention. Future research may determine the long-term effects of the treatment.}, } @article {pmid32995936, year = {2021}, author = {Doello, K and Conde, V and Perez, MC and Mendoza, I and Mesas, C and Prados, J}, title = {Unusual long survival in a case of heterotaxy and polysplenia.}, journal = {Surgical and radiologic anatomy : SRA}, volume = {43}, number = {4}, pages = {607-611}, pmid = {32995936}, issn = {1279-8517}, mesh = {Bone Neoplasms/diagnosis/secondary ; Breast Neoplasms/diagnosis/therapy ; Carcinoma, Ductal, Breast/diagnosis/therapy ; Chemoradiotherapy, Adjuvant ; Contrast Media/administration & dosage ; Female ; Heterotaxy Syndrome/*diagnosis ; Humans ; Incidental Findings ; Liver Neoplasms/diagnosis/secondary ; Mastectomy, Segmental ; Middle Aged ; Spleen/*abnormalities/diagnostic imaging ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.}, } @article {pmid32993586, year = {2020}, author = {Lee, J and Jung, JH and Kim, WW and Park, CS and Lee, RK and Kim, HJ and Kim, WH and Park, HY}, title = {Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {934}, pmid = {32993586}, issn = {1471-2407}, support = {2014R1A5A2009242, 2019R1F1A1063853//National Research Foundation of Korea (NRF) grant funded by the Korea government/ ; 2017M3A9G8083382//National Research Foundation of Korea (NRF) grant funded by the Korea government/ ; 1420040//grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea/ ; HI17C1142//grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea/ ; NRF-2019R1A2C1006264//National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; }, mesh = {Aged ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/pathology/surgery ; Contrast Media/administration & dosage ; *Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Mammography/methods ; Margins of Excision ; Mastectomy, Segmental/methods ; Middle Aged ; }, abstract = {BACKGROUND: Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC).

METHODS: A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans.

RESULTS: Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138).

CONCLUSIONS: Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.}, } @article {pmid32988889, year = {2020}, author = {Yildirim, E and Bektas, S and Gundogar, O and Findik, D and Alcicek, S and Erdogan, KO and Yildiz, M}, title = {The Relationship of GATA3 and Ki-67 With Histopathological Prognostic Parameters, Locoregional Recurrence and Disease-free Survival in Invasive Ductal Carcinoma of the Breast.}, journal = {Anticancer research}, volume = {40}, number = {10}, pages = {5649-5657}, doi = {10.21873/anticanres.14578}, pmid = {32988889}, issn = {1791-7530}, mesh = {Adult ; Biomarkers, Tumor ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Disease-Free Survival ; Estrogens/genetics ; Female ; GATA3 Transcription Factor/*genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Ki-67 Antigen/*genetics ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*genetics/pathology ; Progesterone/genetics ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: In recent years, GATA-binding protein 3 (GATA3) has been indicated as a marker showing good prognosis in breast cancer. In luminal breast cancer, which has good a prognosis, it shows more significant elevation in small-sized and low-grade tumors. In contrast, Ki-67 is defined as a poor prognostic factor. The aim of this study was to emphasise the prognostic importance of GATA3 and the inverse relationship with Ki-67.

MATERIALS AND METHODS: In our study, 90 patients with invasive ductal breast cancer were immunohistochemically evaluated for Ki-67 and GATA3 expression. The relationship between GATA3 and Ki-67 expression was examined. In addition, the relationship between these two factors with estrogen, progesterone, human epidermal growth factor 2 receptor antibodies and other prognostic parameters such as disease-free survival and local recurrence was investigated. We accepted the level of ≥5% nüclear reaction as positive for GATA 3. A Ki-67 cut-off value of 20% was accepted as positive.

RESULTS: In GATA3 positive breast cancers, good prognostic parameters were seen including high estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, small tumor size and low histological grade as well as low Ki-67 expression. In breast cancers showing high Ki-67 expression, ER, PR, and GATA3 positivity were lower and there was higher human epidermal growth factor receptor 2 (HER2) positivity and high histological grade while the tumor size was larger.

CONCLUSION: Our study has revealed that GATA3 has an inverse relationship with Ki-67, whereas it has a positive releationship with good prognostic factors.}, } @article {pmid32983462, year = {2020}, author = {Mallik, D and Ravi, B and Kumar, N and Chattopadhyay, D and Syed, A and Joshi, P}, title = {Invasive ductal carcinoma of breast and squamous cell carcinoma of anterior chest wall-A rare collision.}, journal = {Clinical case reports}, volume = {8}, number = {9}, pages = {1618-1621}, pmid = {32983462}, issn = {2050-0904}, abstract = {Collision tumors are two distinct neoplasms seen together in same anatomic site. Management of such rare entity still lacks standardization with unknown prognosis. Here we are presenting one such rare case of invasive ductal carcinoma of breast and squamous cell carcinoma of anterior chest wall in a 31-year-old lady.}, } @article {pmid32980661, year = {2020}, author = {Lou, B and Boger, M and Bennewitz, K and Sticht, C and Kopf, S and Morgenstern, J and Fleming, T and Hell, R and Yuan, Z and Nawroth, PP and Kroll, J}, title = {Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans.}, journal = {Redox biology}, volume = {37}, number = {}, pages = {101723}, pmid = {32980661}, issn = {2213-2317}, mesh = {*Aldehyde Dehydrogenase/genetics ; Aldehydes ; Animals ; *Diabetes Mellitus ; Gene Knockout Techniques ; Humans ; *Hyperglycemia/genetics ; *Zebrafish/genetics ; }, abstract = {Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1[-/-] zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1[-/-] zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.}, } @article {pmid32979771, year = {2020}, author = {Han, Y and Wang, J and Xu, B}, title = {Clinicopathological characteristics and prognosis of breast cancer with special histological types: A surveillance, epidemiology, and end results database analysis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {114-120}, pmid = {32979771}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/pathology ; Databases, Factual ; Female ; Humans ; Middle Aged ; Neoplasm Grading/*mortality ; Neoplasm Staging/*mortality ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; SEER Program ; Survival Analysis ; }, abstract = {OBJECTIVES: To explore the clinicopathological features and prognosis of breast cancer with special histological types.

MATERIALS AND METHODS: The information of breast cancer patients was obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016). Comparative analyses were performed to explore the difference in clinicopathological characteristics and propensity score matching (PSM) was used to weaken the effects from clinical profiles. Survival analysis was conducted to investigate the prognostic effects from histological types, and the prognostic factors of this group of patients were identified with the univariate COX proportional model.

RESULTS: A total of 242863 breast cancer patients were eligible, of which 230213 individuals were ductal breast cancer (IDC) and 12650 individuals were special breast lesions, respectively. Comparatively, special breast cancer had a lower histological grade, a smaller tumor size, a lower proportion of nodal involvement and distant metastasis, in addition to a higher proportion of triple-negative subtype. The overall prognosis of special histological breast cancer was comparable to IDC, while the survival of HER2 enriched breast cancer was in favor of special breast cancer. With the PSM performance, the prognosis exhibited an inferior profile in the metaplastic breast cancer and was significantly favorable to apocrine, medullary, micropapillary, and papillary breast cancer.

CONCLUSION: This study revealed that the special histological breast cancer presented distinct clinicopathological characteristics and great heterogeneity in the prognosis among diverse histological subtypes.}, } @article {pmid32975612, year = {2020}, author = {Yoshida, Y and Matsumoto, I and Tanaka, T and Yamao, K and Hayashi, A and Kamei, K and Satoi, S and Takebe, A and Nakai, T and Takenaka, M and Takeyama, Y}, title = {Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {222}, pmid = {32975612}, issn = {2198-7793}, abstract = {BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.

CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.

CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.}, } @article {pmid32972772, year = {2020}, author = {Alvarado-Cabrero, I and Valencia-Cedillo, R and Estevez-Castro, R}, title = {Preneoplasia of the Breast and Molecular Landscape.}, journal = {Archives of medical research}, volume = {51}, number = {8}, pages = {845-850}, doi = {10.1016/j.arcmed.2020.09.011}, pmid = {32972772}, issn = {1873-5487}, mesh = {Breast/*pathology ; Breast Neoplasms/*physiopathology ; Female ; Humans ; Hyperplasia/*pathology ; Pathology, Molecular/*methods ; }, abstract = {The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into ductal carcinoma in situ (DCIS) and culminates in the potentially lethal stage of invasive ductal carcinoma. FEA commonly coexists with well-developed examples of ADH, low-grade DCIS, lobular neoplasia and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. At the same time, many of the genomic changes of ADH are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.}, } @article {pmid32968589, year = {2020}, author = {Mandal, S and Bethala, MG and Dadeboyina, C and Khadka, S and Kasireddy, V}, title = {A Rare Presentation of an Invasive Ductal Carcinoma of Ectopic Axillary Breast Tissue.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9928}, pmid = {32968589}, issn = {2168-8184}, abstract = {Ectopic breast tissue (EBT) is a rare entity and can present anywhere along the milk line, including the axilla, inframammary region, thighs, perineum, groin, and vulva. However, the axilla is the most common area of presentation. EBT can present as supernumerary breasts or aberrant breast tissue. Malignancy arising in EBT is rare, but the most common morphological variant is invasive ductal carcinoma. We report a case of a 43-year-old woman, a smoker with a family history of breast cancer, who presented to our clinic with a small mass in the right axillary area. After monitoring it for one year, the mass increased in size, so she returned to the clinic and decided with her care team to excise the mass. Histopathology showed invasive mammary adenocarcinoma arising in EBT and was diagnosed as right accessory stage I breast cancer. This case illustrates the imperative that any mass in the axillary region should be thoroughly assessed to rule out carcinoma in the accessory axillary tissue for timely management.}, } @article {pmid32958157, year = {2020}, author = {Layeequr Rahman, R and Puckett, Y and Habrawi, Z and Crawford, S}, title = {A decade of intraoperative ultrasound guided breast conservation for margin negative resection - Radioactive, and magnetic, and Infrared Oh My….}, journal = {American journal of surgery}, volume = {220}, number = {6}, pages = {1410-1416}, doi = {10.1016/j.amjsurg.2020.09.008}, pmid = {32958157}, issn = {1879-1883}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Female ; Humans ; Intraoperative Period ; Margins of Excision ; Mastectomy/statistics & numerical data ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Reoperation/statistics & numerical data ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: The oncologic goal of margin-negative breast conservation requires adequate localization of tumor. Intraoperative ultrasound remains most feasible but under-utilized method to localize the tumor and assess margins.

METHODS: A prospectively maintained breast cancer database over a decade was queried for margin status in breast cancer patients undergoing breast conservation. Techniques of tumor localization, margin re-excision and closest margins were analyzed. Rate of conversion to mastectomy was determined.

RESULTS: Of the 945 breast cancer patients treated at a university-based Breast Center of Excellence between January 1, 2009 and December 31, 2018, 149(15.8%) had ductal carcinoma in situ; 712(75.3%) had invasive ductal carcinoma, and 63(6.7%) had invasive lobular carcinoma. Clinical stage distribution was: T1 = 372(39.4%); T2 = 257(27.2%); T3 = 87(9.2%). Five hundred and eighty three (61.7%) patients underwent breast conservation. The median (25th -75th centile) closest margin was 6(2.5, 10.0) mm. Thirty five (6.0%) patients underwent margin re-excision, of which 9(25%) were converted to mastectomy. Tumor localization was achieved with ultrasound in 521(89.4%) patients and with wire localization in 62(10.6%) patients. The median (25th-75th centile) closest margin with wire localization was 5.0(2.0, 8.5) mm versus 5.0 (2.0, 8.0) mm with ultrasound guidance [p = 0.6635]. The re-excision rate with wire localization was 14.5% versus 4.9% with ultrasound guidance [p = 0.0073]. The unadjusted Odds Ratio (95% CI) for margin revision in wire localized group compared with ultrasound was 3.2 (7.14, 1.42) [p = 0.0045]; multivariate adjusted OR (95%) was 4(9.09, 1.7) [p = 0.0013].

CONCLUSIONS: Ultrasound guidance for localization of breast cancer remains the most effective option for margin negative breast conservation.}, } @article {pmid32957504, year = {2020}, author = {Griffin, N and Marsland, M and Roselli, S and Oldmeadow, C and Attia, J and Walker, MM and Hondermarck, H and Faulkner, S}, title = {The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer.}, journal = {Biomolecules}, volume = {10}, number = {9}, pages = {}, pmid = {32957504}, issn = {2218-273X}, support = {G1101013//Faculty of Health and Medicine, University of Newcastle Australia/International ; }, mesh = {Biomarkers, Tumor/antagonists & inhibitors/*biosynthesis/genetics ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/metabolism ; Carcinoma, Lobular/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Targeted Therapy/methods ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Receptor, ErbB-2/*metabolism ; Receptor, trkA/antagonists & inhibitors/*biosynthesis/genetics ; Survival Analysis ; }, abstract = {The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.}, } @article {pmid32957459, year = {2020}, author = {Cheung, YC and Chen, SC and Ueng, SH and Yu, CC}, title = {Ductal Carcinoma In Situ Underestimation of Microcalcifications Only by Stereotactic Vacuum-Assisted Breast Biopsy: A New Predictor of Specimens without Microcalcifications.}, journal = {Journal of clinical medicine}, volume = {9}, number = {9}, pages = {}, pmid = {32957459}, issn = {2077-0383}, abstract = {The mammographic appearance of ductal carcinoma in situ (DCIS) is mostly observed as microcalcifications. Although stereotactic vacuum-assisted breast biopsy (VABB) is a reliable alternative to surgical biopsy for suspicious microcalcifications, underestimation of VABB-proven DCIS is inevitable in clinical practice. We therefore retrospectively analyzed the variables in the prediction of DCIS underestimation manifesting as microcalcifications only proved by stereotactic VABB. In 1147 consecutive VABB on microcalcification-only lesions from 2010 to 2016, patients diagnosed with DCIS were selected to evaluate the underestimation rate. The analyzed variables included clinical characteristics, mammographic features, VABB procedure, and biomarkers. Univariate and multivariate analyses were used, and a p value < 0.05 was considered statistically significant. Of the 131 VABB-proven DCIS, 108 cases were diagnosed with DCIS and 23 were upgraded to invasive ductal carcinoma (IDC) after subsequent surgery. The small extent of microcalcification, grouped microcalcifications distribution, nearly complete microcalcification removal, and non-calcified specimens without DCIS were low for DCIS underestimation. Among them, the results of non-calcified specimens with or without DICS were the only statistically significant variables by multivariate logistic regression. These results indicate that the histology of non-calcified specimens was highly predictive of DCIS underestimation. Specimens without DCIS had a low upgrade rate to IDC.}, } @article {pmid32952827, year = {2020}, author = {Methamem, M and Ghadhab, I and Hidar, S and Briki, R}, title = {Breast cancer in men: a serie of 45 cases and literature review.}, journal = {The Pan African medical journal}, volume = {36}, number = {}, pages = {183}, pmid = {32952827}, issn = {1937-8688}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*diagnosis/pathology ; Disease-Free Survival ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/*diagnosis/pathology ; }, abstract = {Immunohistochemical profiling studies carried out on female breast cancer has been extrapolated to breast cancer in males. Although, we do not know if it really reflects the reality of this pathology in males patients since the studies are often retrospective and studying a limited number of patients. The objectives was to describe particualrities of breast cancer in males and analyze the evolutionary characteristics and study the molecular profile of this rare disease in Tunisian men. It is a retrospective, descriptive and analytic study carried out over a period of 15 years in the departments of gynecology-obstetrics, general surgery, medical carcinology and anatomopathology of the Farhat Hached Teaching Hospital in Sousse, Tunisia. Fourty five patients were included.The most common histological type was invasive ductal carcinoma (95% of our patients). Our series was divided into 3 immunohistochemical groups with a majority group: luminal A (68.2%), followed by luminal B (27.3%) and only one patient had a triple negative type tumor (4.5%).The Overall survival rate (OSR) at 5 and 10 years was 83.2% and 76.8% respectively. Recurrence-free survival (RFS) at 5 and 10 years was 64.5% and 58.6%, respectively. The OSR was influenced significantly by age, clinical and histological size of the tumor, the presence of distant metastases and the occurrence of recurrence. Recurrence-free survival (RFS) was influenced by age, clinical and histological size of the tumor, and infiltration of the dermis. Breast cancer in males has similarities with women's breast cancer. However, it remains diagnosed at a later stage.}, } @article {pmid32952761, year = {2020}, author = {Allen, A and Mehta, N and Younes, IE and Singh, M and Green, L and Saran, N}, title = {Multiorgan metastatic invasive lobular Carcinoma initially presenting as diplopia.}, journal = {Radiology case reports}, volume = {15}, number = {11}, pages = {2229-2236}, pmid = {32952761}, issn = {1930-0433}, abstract = {We present an interesting case of biopsy-proven multiorgan metastatic invasive lobular carcinoma to the orbits and kidney, initially presenting in a 76-year-old woman with diplopia. Invasive lobular carcinoma is a less common subtype of breast cancer and is often difficult to detect on imaging with an unusual metastatic pattern when compared to invasive ductal carcinoma. Metastatic invasive lobular carcinoma most frequently involves the orbits, ovaries, gastrointestinal tract, retroperitoneum and bone. Disease involving these organ systems detected on imaging should raise concern for metastatic disease when appropriate.}, } @article {pmid32951175, year = {2021}, author = {Ohno, A and Fujimori, N and Miki, M and Oono, T and Igarashi, H and Matsuda, R and Koga, Y and Oda, Y and Ohtsuka, T and Nakamura, M and Ito, T and Ogawa, Y}, title = {Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1.}, journal = {Clinical journal of gastroenterology}, volume = {14}, number = {1}, pages = {358-363}, pmid = {32951175}, issn = {1865-7265}, mesh = {*Adenocarcinoma/diagnostic imaging/surgery ; *Carcinoma, Pancreatic Ductal/diagnostic imaging/surgery ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; *Neuroendocrine Tumors/diagnostic imaging/surgery ; *Pancreatic Neoplasms/diagnostic imaging/surgery ; }, abstract = {A 54-year-old man with pancreatic head tumor had undergone pancreaticoduodenectomy and was diagnosed with pancreatic neuroendocrine tumor (P-NET) associated with sporadic multiple endocrine neoplasm type 1. Five years after the resection, P-NET recurred and liver metastases were observed. He was treated with a somatostatin analog. Eleven years after the resection, computed tomography revealed a new pancreatic hypodense and hypovascular mass adjacent to the P-NET that was diagnosed as pancreatic adenocarcinoma via endoscopic ultrasound-guided fine-needle aspiration. He underwent a total remnant pancreatectomy. Pathological examination showed that the lesion was constituted by a pancreatic ductal adenocarcinoma (PDAC) and a neuroendocrine tumor. Additionally, the invasive ductal carcinoma collided with the neuroendocrine tumor. Both PDAC and P-NET cells were observed in the collision area. We could observe the onset of PDAC during the treatment of P-NET. Moreover, we are the first to report the case of a collision of pancreatic endocrine and exocrine tumors diagnosed preoperatively.}, } @article {pmid32947148, year = {2020}, author = {Zhang, J and Lu, CY and Chen, CH and Chen, HM and Wu, SY}, title = {Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {54}, number = {}, pages = {70-78}, pmid = {32947148}, issn = {1532-3080}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; *Radiotherapy, Adjuvant ; Registries ; Regression Analysis ; Taiwan ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).

PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.

RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P < 0.0001) and 0.58 (0.47-0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P < 0.0001), 0.60 (0.40-0.88, P = 0.0096), and 0.64 (0.48-0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.

CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.}, } @article {pmid32944466, year = {2020}, author = {Sohail, SK and Sarfraz, R and Imran, M and Kamran, M and Qamar, S}, title = {Estrogen and Progesterone Receptor Expression in Breast Carcinoma and Its Association With Clinicopathological Variables Among the Pakistani Population.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9751}, pmid = {32944466}, issn = {2168-8184}, abstract = {Introduction The prognosis of breast cancer depends on the histological type, size of the tumor, tumor necrosis, skin, nipple and chest wall invasion, lymphovascular invasion, grade, stage, the status of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2), cell proliferation marker (ki-67), and type of therapy. Estrogen receptor and progesterone receptor expression in breast cancer is, so far, the most useful predictive marker. We have undertaken this study to find the expression of ER and PgR in breast carcinoma and its association with other prognostically important clinicopathological variables. Materials and methods In this cross-sectional study, a total of 130 cases of modified radical mastectomy that have been diagnosed as malignant on histopathology were collected from the pathology department of Allama Iqbal Medical College, Lahore, from January 2016 to May 2018. The demographic data and gross and microscopic findings were recorded. Immunohistochemistry (ER, PgR) was applied to suitable tumor sections and their status was evaluated semi-quantitatively by histopathologists using College American Pathologist (CAP) guidelines. Result Most of the breast cancer patients (69; 53.1%) were below 50 years of age. Fifty-nine (45.4%) and 48 (36.9%) cases were positive for ER and PgR, respectively, showing lower hormonal receptor positivity than that reported in the western population where ER expression has been found in 50%-80% of cases and PR expression is found in 60%-70% of cases of invasive ductal carcinoma. The association of the expression of hormone receptors with a clinicopathological variable was demonstrated. ER-/PgR- tumors showed a higher histologic grade, greater tumor size, and more lymph node involvement by metastasis. Conclusion Low hormone receptor positivity is associated with young patients, advanced stage at presentation, and higher grade in our population. The tumor characteristics are different as compared to the western population. This suggests more consideration to the screening, early diagnosis, and molecular or immunohistochemical typing of this cancer in our population.}, } @article {pmid32943456, year = {2020}, author = {Richard, F and Majjaj, S and Venet, D and Rothé, F and Pingitore, J and Boeckx, B and Marchio, C and Clatot, F and Bertucci, F and Mariani, O and Galant, C and Eynden, GVD and Salgado, R and Biganzoli, E and Lambrechts, D and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C and Desmedt, C}, title = {Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {23}, pages = {6254-6265}, doi = {10.1158/1078-0432.CCR-20-2268}, pmid = {32943456}, issn = {1557-3265}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/immunology/metabolism/*secondary ; Carcinoma, Lobular/genetics/immunology/metabolism/*secondary ; Female ; Follow-Up Studies ; Genomics/*methods ; Humans ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Stromal Cells/*immunology ; Survival Rate ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.

EXPERIMENTAL DESIGN: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT.

RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases.

CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.}, } @article {pmid32931396, year = {2020}, author = {Weinstein, SP and Korhonen, K and Cirelli, C and Schnall, MD and McDonald, ES and Pantel, AR and Zuckerman, S and Borthakur, A and Conant, EF}, title = {Abbreviated Breast Magnetic Resonance Imaging for Supplemental Screening of Women With Dense Breasts and Average Risk.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {38}, number = {33}, pages = {3874-3882}, doi = {10.1200/JCO.19.02198}, pmid = {32931396}, issn = {1527-7755}, mesh = {Adult ; Aged ; Biopsy/methods ; Breast/*diagnostic imaging/*pathology ; Breast Density ; Breast Neoplasms/*diagnostic imaging/pathology ; Early Detection of Cancer/methods ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: Although mammography is the standard of care for breast cancer screening, dense breast tissue decreases mammographic sensitivity. We report the prevalent cancer detection rate (CDR) from the first clinical implementation of abbreviated breast magnetic resonance imaging (AB-MR) as a supplemental screening test in women with dense breasts.

METHODS: The study was approved by the institutional review board and is Health Insurance Portability and Accountability Act complaint. This retrospective review includes women who were imaged between January 1, 2016 and February 28, 2019. On a 1.5 Tesla magnet, the imaging protocol consisted of three sequences: Short-TI Inversion Recovery (STIR), precontrast, and postcontrast. A subtraction sequence and a maximum intensity projection were generated. We report the patient-level CDR and the positive predictive value of AB-MR examinations after negative/benign digital breast tomosynthesis (DBT).

RESULTS: Out of 511 prevalent rounds of AB-MR examinations, 36 women were excluded. The remaining 475 asymptomatic women with dense breasts had negative/benign DBT examinations before the AB-MR. There were 420 of 475 (88.4%) benign/negative examinations, 13 of 475 (2.7%) follow-up recommendations, and 42 biopsy recommendations. Thirty-nine biopsies were completed, resulting in 12/39 (30.8%) malignancies in 12 women: seven invasive carcinomas and five ductal carcinoma in situ. One additional patient was diagnosed with invasive ductal carcinoma at the time of 6-month follow-up. The CDR was 27.4 per 1,000 (13 of 475; 95% CI, 16.1 to 46.3). The size of invasive carcinomas ranged from 0.6-1.0 cm (mean, 0.5 cm). Of the seven women who underwent surgical evaluation of the axilla, zero of seven patients had positive nodes. There were no interval cancers at 1-year follow-up.

CONCLUSION: Preliminary results from clinical implementation of screening AB-MR resulted in a CDR of 27.4/1,000 at the patient level after DBT in women with dense breasts. Additional evaluation is warranted.}, } @article {pmid32931030, year = {2021}, author = {Taverna, C and Baněčková, M and Lorenzon, M and Palomba, A and Franchi, A and Skalova, A and Agaimy, A}, title = {MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.}, journal = {Histopathology}, volume = {79}, number = {3}, pages = {315-324}, doi = {10.1111/his.14251}, pmid = {32931030}, issn = {1365-2559}, mesh = {Biomarkers, Tumor/analysis ; Carcinoma/diagnosis/pathology ; Carcinoma, Acinar Cell/diagnosis/pathology ; *Diagnosis, Differential ; Humans ; Mammaglobin A/metabolism ; Mammary Analogue Secretory Carcinoma/*diagnosis/metabolism/pathology ; Mucin-4/*analysis ; *Salivary Gland Neoplasms/diagnosis/metabolism/pathology ; Salivary Glands/pathology ; }, abstract = {AIMS: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin.

METHODS AND RESULTS: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high-grade SCs lost MUC4 expression in the high-grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK versus non-ETV6-NTRK).

CONCLUSION: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.}, } @article {pmid32923781, year = {2020}, author = {Cruz, C and Vega Carvallo, AI and Spodine, E and Escuer, A and Marco, JF and Menéndez, N and Venegas-Yazigi, D and Paredes-García, V}, title = {New Highly Charged Iron(III) Metal-Organic Cube Stabilized by a Bulky Amine.}, journal = {ACS omega}, volume = {5}, number = {35}, pages = {22238-22247}, pmid = {32923781}, issn = {2470-1343}, abstract = {In this work, we report a new octanuclear cluster based on Fe[III] and the ligand 1H-imidazole-4,5-dicarboxylic acid, [Et3NH]12[Fe8(IDC)12]·10DMF·13H2O (1), with a metal core containing eight Fe[III] connected by only one type of organic ligand. A peak at 573 m/z in the mass spectra of the compound suggests the adduct species {[Fe8(IDC)12]+8H} [4-]. By X-ray photoelectron spectroscopy, the oxidation state of the iron cation was confirmed to be 3+, also identifying the presence of a quaternary nitrogen species, which act as a countercation of the anionic metal core [Fe8(IDC)12][12-]. Mössbauer spectra recorded at different temperatures show an isomer shift and quadrupole splitting parameters that confirm the existence of only Fe[III]-HS in the structure of 1. X-ray analysis reveals that compound 1 crystallizes in the orthorhombic system space group Ibam, confirming a molecular cluster structure with an almost regular cube as geometry, with the Fe[III] atoms located at the corners of the cube and connected by μ-1κ[2] N,O:2κ[2] N',O‴-IDC[3-] bridges. Additionally, the magnetic measurements reveal a weak antiferromagnetic coupling in the Fe8 [III] coordination cluster (J = -3.8 cm[-1]). To the best of our knowledge, 1 is the first member of the family of cubes assembled with 1H-imidazole-4,5-dicarboxylic acid and Fe[III] cation, exhibiting high pH stability over a broad pH range, making it an ideal candidate for the design of supramolecular structures and metal-organic frameworks.}, } @article {pmid32923401, year = {2020}, author = {Xu, N and Ke, ZB and Chen, YH and Wu, YP and Chen, SH and Wei, Y and Zheng, QS and Huang, JB and Li, XD and Xue, XY}, title = {Risk Factors for Pathologically Confirmed Lymph Nodes Metastasis in Patients With Clinical T2N0M0 Stage Prostate Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1547}, pmid = {32923401}, issn = {2234-943X}, abstract = {OBJECTIVE: To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa).

METHODS: We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score.

RESULTS: A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ≥ 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ≥ 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden.

CONCLUSION: There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ≥ 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ≥ 3.}, } @article {pmid32920553, year = {2020}, author = {Bartlett, H and Elghobashy, M and Deshmukh, N and Rao, R and Shaaban, AM}, title = {Radiation-Associated Primary Osteosarcoma of the Breast.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {5}, pages = {322-326}, doi = {10.1159/000509580}, pmid = {32920553}, issn = {1423-0291}, mesh = {Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/*etiology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Osteosarcoma/*diagnostic imaging/*etiology/surgery ; Radiation Injuries/complications ; Radiotherapy/*adverse effects ; }, abstract = {INTRODUCTION: Non-epithelial primary mammary osteosarcomas are extremely rare. The differentials include metaplastic carcinoma and malignant phyllodes tumour. This is the first published case of primary breast osteosarcoma arising after local radiotherapy.

CASE PRESENTATION: A 73-year-old female presented with a right-sided breast lump. The same breast had been irradiated 11 years previously for invasive ductal carcinoma. Diagnostic excision revealed a highly cellular, malignant spindle-cell lesion merged with an osteoid matrix and foci of calcification and bone formation. Immunohistochemistry and molecular studies showed no lines of differentiation. Due to the lack of epithelial/glandular differentiation, in situ carcinoma or leaf-like pattern, the diagnosis of post-irradiation osteosarcoma was made. She underwent mastectomy and is disease-free at 8 months of follow-up.

CONCLUSION: Post-irradiation osteosarcoma should be considered in the differential diagnosis of breast lesions showing malignant osteoid. Extensive sampling and careful search for epithelial differentiation is required to guide management. Complete surgical excision is recommended.}, } @article {pmid32920164, year = {2020}, author = {Aboody, D and Siev, J and Doron, G}, title = {Building resilience to body image triggers using brief cognitive training on a mobile application: A randomized controlled trial.}, journal = {Behaviour research and therapy}, volume = {134}, number = {}, pages = {103723}, doi = {10.1016/j.brat.2020.103723}, pmid = {32920164}, issn = {1873-622X}, mesh = {Adult ; Body Dissatisfaction/*psychology ; Body Dysmorphic Disorders/psychology/*therapy ; Body Image/*psychology ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; *Mobile Applications ; *Resilience, Psychological ; *Social Media ; Young Adult ; }, abstract = {OBJECTIVE: Body image disturbance (BID) is common among women, characterized by persistent and distressing appearance dissatisfaction, and linked with eating disorders. Although effective, cognitive behavioral therapy (CBT) delivered by trained professionals is not easily accessible. This randomized trial evaluated the effects of a CBT-based mobile application designed to increase resilience to body image triggers and reduce BID symptoms.

METHOD: A non-clinical sample of women (N = 90; Mage = 23.52) was randomized to use the mobile application for approximately 4 min of daily exercises for two weeks or to a control condition. Body image was measured at baseline, immediately after two weeks of mobile application use, and at 1-month follow-up. To examine whether using the application was associated with increased resilience to common BID triggers, participants completed an Instagram exposure resilience task upon completion and at 1-month follow-up.

RESULTS: Relative to those in the control condition, participants who used the application demonstrated increased resiliency and reduced BID symptoms. Theses effects were medium-to-large and were maintained at 1-month follow-up.

CONCLUSION: These results underscore the potential usefulness of brief, low-intensity, portable interventions in reducing BID symptoms and in increasing resilience to thin-ideal body messages often portrayed on social media.}, } @article {pmid32917802, year = {2021}, author = {Larson, AS and Cloft, H and Carabenciov, ID and Lanzino, G}, title = {Teaching NeuroImages: The Venous System and Developmental Venous Anomalies: Drivers of Vascular Malformations?.}, journal = {Neurology}, volume = {96}, number = {6}, pages = {e960-e961}, doi = {10.1212/WNL.0000000000010815}, pmid = {32917802}, issn = {1526-632X}, mesh = {Angiography, Digital Subtraction ; Arteriovenous Fistula/*diagnostic imaging ; Female ; Humans ; Intracranial Arteriovenous Malformations/*diagnostic imaging ; Middle Aged ; Neuroimaging/methods ; }, } @article {pmid32911313, year = {2020}, author = {Ucar, EA and Durur-Subasi, I and Yilmaz, KB and Arikok, AT and Hekimoglu, B}, title = {Quantitative perfusion parameters of benign inflammatory breast pathologies: A descriptive study.}, journal = {Clinical imaging}, volume = {68}, number = {}, pages = {249-256}, doi = {10.1016/j.clinimag.2020.08.024}, pmid = {32911313}, issn = {1873-4499}, mesh = {*Breast/diagnostic imaging ; *Contrast Media ; Humans ; Magnetic Resonance Imaging ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {PURPOSE: With this study, we evaluated the perfusion magnetic resonance imaging (MRI) features of benign inflammatory breast lesions for the first time and compared their Ktrans, Kep, Ve values and contrast kinetic curves to benign masses and invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: Perfusion MRIs of the benign masses (n = 42), inflammatory lesions (n = 25), and IDCs (n = 16) were evaluated retrospectively in terms of Ktrans, Kep, Ve values and contrast kinetic curves and compared by the Kruskal-Wallis, Mann-Whitney U, chi-square tests statistically. Cronbach α test was used to measure intraobserver and interobserver reliability.

RESULTS: Mean Ktrans values were 0.052 for benign masses, 0.086 for inflammatory lesions and 0.101 for IDC (p < 0.001). Mean Kep values were 0.241 for benign masses, 0.435 for inflammatory lesions and 0.530 for IDC (p < 0.001). Mean Ve values were 0.476 for benign masses, 0.318 for inflammatory lesions and 0.310 for IDC (p = 0.067). For inflammatory and IDC lesions, Ktrans and Kep values were found to be higher and Ve values were lower than benign masses (p = 0.001 for Ktrans, p = 0.001 for Kep, p = 0.045 for Ve). There were excellent or good intra-interobserver reliabilities. For the kinetic curve pattern, most of the benign lesions showed progressive (81%), inflammatory lesions progressive (64%) and IDC lesions plateau (75%) patterns (p < 0.001).

CONCLUSIONS: On T1 perfusion MRI, similar to IDC lesions, inflammatory lesions demonstrate higher Ktrans and Kep and lower Ve values than benign masses. Quantitative perfusion parameters are not helpful in differentiating them from IDC lesions.}, } @article {pmid32908789, year = {2020}, author = {Cha, YJ and Koo, JS}, title = {Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.}, journal = {Journal of breast cancer}, volume = {23}, number = {4}, pages = {385-397}, pmid = {32908789}, issn = {1738-6756}, abstract = {PURPOSE: Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications.

METHODS: In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data.

RESULTS: EMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index.

CONCLUSION: EMP2 may be involved in the early stage of tumor development in hormone-positive breast cancer.}, } @article {pmid32908506, year = {2020}, author = {Verma, AK and Ahmad, I and Yadav, P and Rahmani, AH and Khan, B and Alsahli, MA and Joshi, PC and Ahmad, H and Ali Beg, MM}, title = {Expression and Correlation of Cell-Free cIAP-1 and cIAP-2 mRNA in Breast Cancer Patients: A Study from India.}, journal = {Journal of oncology}, volume = {2020}, number = {}, pages = {3634825}, pmid = {32908506}, issn = {1687-8450}, abstract = {BACKGROUND: Inhibitors of apoptosis proteins such as cIAP-1 and cIAP-2 have recently emerged as the key mechanism in resistance to apoptosis in various cancers and lead to cell survival. Therefore, the present study aimed to evaluate the cIAP-1 and cIAP-2 expression in breast cancer patients, as well as their association with overall patient survival.

METHODS: Histopathologically confirmed 100 invasive ductal carcinoma patients and healthy controls were included in the present study. Total RNA extraction was done from the serum sample of the patients; further, 100 ng of total RNA was used to synthesise cDNA from patients' as well as from healthy controls' serum. Quantitative real-time PCR was performed using the maxima SYBR Green dye to study the expression of cIAP-1 and cIAP-2, and beta-actin was used as the internal control.

RESULTS: The study observed that breast cancer patients had 13.50 mean fold increased cIAP-1 mRNA and 8.76 mean fold increased cIAP-2 mRNA expression compared to the control subjects. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p=0.004). Distant organ metastasis, (p=0.008), PR status of breast cancer patients (p < 0.0001), and HER2 status of breast cancer patients (p < 0.0001) were found to be associated with cIAP-1 mRNA expression. Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p=0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p < 0.0001). Breast cancer patients with <13-fold and >13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p=0.0001). However, cIAP-2 mRNA expression among <8-fold and >8-fold mRNA expression groups showed 35 months and 27.90 months of overall median survival time (p < 0.0001). Higher cIAP-1 mRNA expression was linked with smoking and alcoholism among the breast cancer patients (p < 0.0001 and p < 0.0001). Significant association of higher cIAP-1 mRNA expression was found with the advancement of the disease, while higher mRNA expression of cIAP-1 was associated with distant organ metastases in ROC curve analysis.

CONCLUSION: The present study suggested that increased cell-free cIAP-1 and cIAP-2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease.}, } @article {pmid32907600, year = {2020}, author = {Israelov, H and Ravid, O and Atrakchi, D and Rand, D and Elhaik, S and Bresler, Y and Twitto-Greenberg, R and Omesi, L and Liraz-Zaltsman, S and Gosselet, F and Schnaider Beeri, M and Cooper, I}, title = {Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair.}, journal = {Journal of neuroinflammation}, volume = {17}, number = {1}, pages = {267}, pmid = {32907600}, issn = {1742-2094}, support = {11816372//Defense Threat Reduction Agency/ ; 3-13576//Ministry of Science and Technology, Israel/ ; }, mesh = {Animals ; Blood-Brain Barrier/drug effects/injuries/*metabolism ; Caspase 1/*metabolism ; Cell Death/physiology ; Cell Movement/physiology ; Coculture Techniques ; Dipeptides/pharmacology ; Endothelial Cells/*metabolism ; Humans ; Inflammasomes/*metabolism ; Interleukin-8/metabolism ; Male ; Mice ; Pericytes/*metabolism ; para-Aminobenzoates/pharmacology ; }, abstract = {BACKGROUND: Excessive inflammation might activate and injure the blood-brain barrier (BBB), a common feature of many central nervous system (CNS) disorders. We previously developed an in vitro BBB injury model in which the organophosphate paraoxon (PX) affects the BBB endothelium by attenuating junctional protein expression leading to weakened barrier integrity. The objective of this study was to investigate the inflammatory cellular response at the BBB to elucidate critical pathways that might lead to effective treatment in CNS pathologies in which the BBB is compromised. We hypothesized that caspase-1, a core component of the inflammasome complex, might have important role in BBB function since accumulating evidence indicates its involvement in brain inflammation and pathophysiology.

METHODS: An in vitro human BBB model was employed to investigate BBB functions related to inflammation, primarily adhesion and transmigration of peripheral blood mononuclear cells (PBMCs). Caspase-1 pathway was studied by measurements of its activation state and its role in PBMCs adhesion, transmigration, and BBB permeability were investigated using the specific caspase-1 inhibitor, VX-765. Expression level of adhesion and junctional molecules and the secretion of pro-inflammatory cytokines were measured in vitro and in vivo at the BBB endothelium after exposure to PX. The potential repair effect of blocking caspase-1 and downstream molecules was evaluated by immunocytochemistry, ELISA, and Nanostring technology.

RESULTS: PX affected the BBB in vitro by elevating the expression of the adhesion molecules E-selectin and ICAM-1 leading to increased adhesion of PBMCs to endothelial monolayer, followed by elevated transendothelial-migration which was ICAM-1 and LFA-1 dependent. Blocking caspase-8 and 9 rescued the viability of the endothelial cells but not the elevated transmigration of PBMCs. Inhibition of caspase-1, on the other hand, robustly restored all of barrier insults tested including PBMCs adhesion and transmigration, permeability, and VE-cadherin protein levels. The in vitro inflammatory response induced by PX and the role of caspase-1 in BBB injury were corroborated in vivo in isolated blood vessels from hippocampi of mice exposed to PX and treated with VX-765.

CONCLUSIONS: These results shed light on the important role of caspase-1 in BBB insult in general and specifically in the inflamed endothelium, and suggest therapeutic potential for various CNS disorders, by targeting caspase-1 in the injured BBB.}, } @article {pmid32907593, year = {2020}, author = {Alan, O and Akin Telli, T and Aktas, B and Koca, S and Ökten, IN and Hasanov, R and Basoglu, T and Arikan, R and Demircan, NC and Ercelep, O and Kaya, S and Ugurlu, MU and Kaya, H and Akgul Babacan, N and Dane, F and Yumuk, PF}, title = {Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?.}, journal = {World journal of surgical oncology}, volume = {18}, number = {1}, pages = {242}, pmid = {32907593}, issn = {1477-7819}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy ; Humans ; *Insulin Resistance ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment.

METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated.

RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01].

CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.}, } @article {pmid32904995, year = {2020}, author = {Kobayashi, T and Marra, AR and Schweizer, ML and Ten Eyck, P and Wu, C and Alzunitan, M and Salinas, JL and Siegel, M and Farmakiotis, D and Auwaerter, PG and Healy, HS and Diekema, DJ}, title = {Impact of Infectious Disease Consultation in Patients With Candidemia: A Retrospective Study, Systematic Literature Review, and Meta-analysis.}, journal = {Open forum infectious diseases}, volume = {7}, number = {9}, pages = {ofaa270}, pmid = {32904995}, issn = {2328-8957}, support = {UL1 TR002537/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Morbidity and mortality from candidemia remain unacceptably high. While infectious disease consultation (IDC) is known to lower the mortality from Staphylococcus aureus bacteremia, little is known about the impact of IDC in candidemia.

METHODS: We conducted a retrospective observational cohort study of candidemia patients at a large tertiary care hospital between 2015 and 2019. The crude mortality rate was compared between those with IDC and without IDC. Then, we systematically searched 5 databases through February 2020 and performed a meta-analysis of the impact of IDC on the mortality of patients with candidemia.

RESULTS: A total of 151 patients met the inclusion criteria, 129 (85%) of whom received IDC. Thirty-day and 90-day mortality rates were significantly lower in the IDC group (18% vs 50%; P = .002; 23% vs 50%; P = .0022, respectively). A systematic literature review returned 216 reports, of which 13 studies including the present report fulfilled the inclusion criteria. Among the 13 studies with a total of 3582 patients, IDC was performed in 50% of patients. Overall mortality was 38.2% with a significant difference in favor of the IDC group (28.4% vs 47.6%), with a pooled relative risk of 0.41 (95% CI, 0.35-0.49). Ophthalmology referral, echocardiogram, and central line removal were performed more frequently among patients receiving IDC.

CONCLUSIONS: This study is the first systematic literature review and meta-analysis to evaluate the association between IDC and candidemia mortality. IDC was associated with significantly lower mortality and should be considered in all patients with candidemia.}, } @article {pmid32898519, year = {2020}, author = {Aggius-Vella, E and Gori, M and Animali, S and Campus, C and Binda, P}, title = {Non-spatial skills differ in the front and rear peri-personal space.}, journal = {Neuropsychologia}, volume = {147}, number = {}, pages = {107619}, doi = {10.1016/j.neuropsychologia.2020.107619}, pmid = {32898519}, issn = {1873-3514}, mesh = {*Auditory Perception ; Humans ; *Personal Space ; Pupil ; Sound ; }, abstract = {In measuring behavioural and pupillary responses to auditory oddball stimuli delivered in the front and rear peri-personal space, we find that pupils dilate in response to rare stimuli, both target and distracters. Dilation in response to targets is stronger than the response to distracters, implying a task relevance effect on pupil responses. Crucially, pupil dilation in response to targets is also selectively modulated by the location of sound sources: stronger in the front than in the rear peri-personal space, in spite of matching behavioural performance. This supports the concept that even non-spatial skills, such as the ability to alert in response to behaviourally relevant events, are differentially engaged across subregions of the peri-personal space.}, } @article {pmid32896509, year = {2020}, author = {Okun, JG and Conway, S and Schmidt, KV and Schumacher, J and Wang, X and de Guia, R and Zota, A and Klement, J and Seibert, O and Peters, A and Maida, A and Herzig, S and Rose, AJ}, title = {Corrigendum to "Molecular regulation of urea cycle function by the liver glucocorticoid receptor" [Mol Metab 4 (10) (2015 Oct) 732-740].}, journal = {Molecular metabolism}, volume = {41}, number = {}, pages = {101068}, doi = {10.1016/j.molmet.2020.101068}, pmid = {32896509}, issn = {2212-8778}, } @article {pmid32888139, year = {2020}, author = {Amitai, Y and Menes, TS and Scaranelo, A and Fleming, R and Kulkarni, S and Ghai, S and Cil, T and Done, S and Freitas, V}, title = {Lobular neoplasia occult on conventional imaging and diagnosed on MRI-guided biopsy: can we estimate upgrade on surgical pathology?.}, journal = {Breast cancer research and treatment}, volume = {184}, number = {3}, pages = {881-890}, doi = {10.1007/s10549-020-05893-y}, pmid = {32888139}, issn = {1573-7217}, mesh = {Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnostic imaging/epidemiology ; *Carcinoma, Lobular/diagnostic imaging/surgery ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging ; *Pathology, Surgical ; *Precancerous Conditions ; Retrospective Studies ; }, abstract = {PURPOSE: The goal of this study is to evaluate the frequency and imaging features of lobular neoplasia (LN) diagnosed on MRI-guided biopsy, determine the upgrade rate to malignancy, and assess for any features that may be associated with an upgrade on surgical excision.

MATERIALS AND METHODS: Research ethical board approved the review of consecutive patients with MRI-detected LN between January 2009 and December 2018 with differentiation between pure LN and LN with associated other high-risk lesions. The final outcome was determined by final pathology results from surgical excision or 24 months of follow-up. Appropriate statistical tests were used.

RESULTS: Out of 1250 MRI-guided biopsies performed, 76 lesions (6%) fulfilled the inclusion criteria and formed the study cohort. Of the 76 lesions, 54 (71%) were pure LN while the rest had coexistent high-risk lesion. Non-mass enhancement (NME) was the most common lesion type (62, 82%). Fifty-nine lesions (78%) were surgically excised, the other 17 had benign follow-up. Overall, 8 lesions (11%) were upgraded to malignancy on final pathology. Malignant outcome was associated with larger lesion size (5.5 versus 1.9 cm, P < 0.001) and a clumped NME pattern (75% versus 24%, P = 0.006). Lesion size and clumped NME remained significantly associated with upgrade on sub-analysis of the pure LN group.

CONCLUSION: Larger lesion size and clumped NME are imaging findings associated with upgrade of LN diagnosed by MRI-guided biopsy. This may influence patient management in this clinical setting. Additional larger studies are needed to consolidate our results and to potentially detect additional factors associated with upgrade.}, } @article {pmid32885737, year = {2020}, author = {Hirabayashi, M and Chambers, JK and Sumi, A and Harada, K and Haritani, M and Omachi, T and Kobayashi, T and Nakayama, H and Uchida, K}, title = {Immunophenotyping of Nonneoplastic and Neoplastic Histiocytes in Cats and Characterization of a Novel Cell Line Derived From Feline Progressive Histiocytosis.}, journal = {Veterinary pathology}, volume = {57}, number = {6}, pages = {758-773}, doi = {10.1177/0300985820953538}, pmid = {32885737}, issn = {1544-2217}, mesh = {Animals ; *Cat Diseases ; Cats ; Cell Line ; Histiocytes ; *Histiocytic Sarcoma/veterinary ; Immunohistochemistry ; *Immunophenotyping/veterinary ; Tumor Microenvironment ; }, abstract = {Histiocytic proliferative diseases are rare in cats, and their pathogenesis is poorly understood. In the present study, 25 cases of histiocytic sarcoma (HS) and 6 of feline progressive histiocytosis (FPH) were examined, and survival times were recorded in 19 cases. The immunophenotypes of tumor cells in these cases as well as of nonneoplastic feline histiocytes were characterized using formalin-fixed, paraffin-embedded tissues. An FPH cell line (AS-FPH01) and xenotransplant mouse model of FPH were also established. The median survival time of HS (150 days) was significantly shorter than that of FPH (470 days). Immunohistochemically, nonneoplastic histiocytes were immunopositive for various combinations of Iba-1, HLA-DR, E-cadherin, CD204, CD163, CD208, and MAC387. By immunohistochemistry, dermal interstitial dendritic cells (iDCs) and macrophages were CD204+/E-cadherin-, while epidermal Langerhans cells (LCs) were CD204-/E-cadherin+. Neoplastic cells of 4 FPH and 18 HS were CD204+/E-cadherin- (iDC/macrophage immunophenotype), while 2 FPH and 2 HS were CD204-/E-cadherin+ (LC immunophenotype), and 5 HS were CD204+/E-cadherin+ (LC-like cell immunophenotype). Furthermore, immunohistochemical and western blot analyses of AS-FPH01 cells derived from E-cadherin-negative FPH revealed that cultured cells were immunopositive for both CD204 and E-cadherin in vitro and in vivo. These results indicate that the neoplastic cells of feline HS and FPH were variably positive for iDC/macrophage and LC markers, and their immunophenotype changed in different microenvironments. The novel cell line established in the present study may serve as an experimental model of FPH that will enable further molecular and therapeutic studies on this disease.}, } @article {pmid32884870, year = {2020}, author = {Sharma, S and Blaudeau, E and Sharma, S}, title = {A Case of Asymmetric Nipple Enhancement as an Imaging Precursor to Invasive Ductal Carcinoma.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9514}, pmid = {32884870}, issn = {2168-8184}, abstract = {On multidetector computed tomography (CT), it is important to scrutinize the imaged portions of the breasts. In recent years, the dramatic rise in CT imaging has led to the increased detection of incidental breast lesions. We describe a case of invasive ductal carcinoma that presented as stage IV cancer, and retrospective review of prior imaging study revealed asymmetric nipple enhancement on a trauma protocol CT chest acquired three years earlier. This report highlights the importance of being attentive to breast abnormalities on CT performed for indications other than breast disease and additionally focuses on the approach to address abnormal enhancement of the nipple areolar complex (NAC).}, } @article {pmid32884540, year = {2020}, author = {Ramdas, Y and Benn, CA and Grubnik, A and Mayat, Y and Holmes, DR}, title = {Targeted Intraoperative Radiotherapy Is a Safe Approach for Patients with Pacemakers: A Case Study and Literature Review.}, journal = {Case reports in oncology}, volume = {13}, number = {2}, pages = {916-922}, pmid = {32884540}, issn = {1662-6575}, abstract = {Case reports detailing the effects of targeted intraoperative radiation therapy (IORT) on patients with cardiac pacemakers (PMs) are rare. This growing population sub-group requiring IORT and lack of standardized guidelines necessitate more practical published research. An 81-year-old patient with clinical stage II, T1 N0 grade III, triple-negative invasive ductal carcinoma and an implanted single-lead chamber PM (VVIR mode, model: Biotronik, type Effecta SR) received targeted intraoperative radiotherapy at the time of wide local excision and sentinel lymph node biopsy. It presents the shortest distance between the outer diameter of the PM and IORT applicator in literature. Target IORT was performed utilizing an Intrabeam device (50 kV, Carl Zeiss Surgical, Oberkochen, Germany). This case elucidates the successful use of targeted IORT for breast-conserving surgery in a patient with a single ipsilateral chamber VVIR mode PM. No device failure or malfunction was reported for the PM before, during, or after the procedure. These findings support the use of targeted IORT for patients diagnosed with early-stage breast carcinomas who have a PM implanted. However, further research is needed to understand the safety of other methods and devices for IORT patients with cardiac implantable electronic devices.}, } @article {pmid32884534, year = {2020}, author = {Liu, IC and Giap, F and Mailhot-Vega, RB and Bradley, JA and Mendenhall, NP and Okunieff, P and Lu, L and Jantz, MA and Daily, K and Spiguel, L and Lockney, NA}, title = {Concomitant Radiation Recall Dermatitis and Organizing Pneumonia following Breast Radiotherapy: A Case Report.}, journal = {Case reports in oncology}, volume = {13}, number = {2}, pages = {875-882}, pmid = {32884534}, issn = {1662-6575}, abstract = {PURPOSE: Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction.

PATIENT: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2- invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0.

RESULT: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration.

CONCLUSIONS: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.}, } @article {pmid32880425, year = {2020}, author = {Othong, J and Boonmak, J and Kielar, F and Youngme, S}, title = {Dual Function Based on Switchable Colorimetric Luminescence for Water and Temperature Sensing in Two-Dimensional Metal-Organic Framework Nanosheets.}, journal = {ACS applied materials & interfaces}, volume = {12}, number = {37}, pages = {41776-41784}, doi = {10.1021/acsami.0c12014}, pmid = {32880425}, issn = {1944-8252}, abstract = {A simple, rapid, highly selective, and real-time determination of water is urgently required for preventing danger from water contamination in materials. Herein, the excited-state proton transfer (ESPT) concept-based luminescent sensor [Cd2(2,5-tpt)(4,5-idc)(H2O)4] (1) (2,5-tpt = 2,5-dihydroxyterephthalic acid and 4,5-idc = 4,5-imidazoledicarboxylic acid) has been designed for discriminative detection via enol-keto tautomerism. To improve the sensitivity, two-dimensional (2D) nanosheets of 1 have been synthesized by top-down liquid ultrasonic exfoliation technology for sensing water in dimethylformamide, which lead to fast detection (<30 s), high selectivity, broad-range detection (0-50% v/v), and a low detection limit value (0.25% v/v). This sensor can serve dual sensing mechanisms along with a luminescent color change via shifted emission (green→yellow) in low water content and a turn-off method in high water content. For ease of use, the test-strip paper-based 2D nanosheets of 1 have been prepared and applied for water detection with long-term stability, pH stability, and good reusability. On-site water detection in real time can be evaluated using a smartphone color-scanning application for quantitative scanometric assays coupled with test-strip paper-based 2D nanosheets of 1. Also, 1 can be utilized for a colorimetric luminescent thermometer in the ranges of physiological and high temperature with good linearity and recyclability.}, } @article {pmid32877689, year = {2020}, author = {Rohm, M and Herzig, S}, title = {An Antibody Attack against Body Wasting in Cancer.}, journal = {Cell metabolism}, volume = {32}, number = {3}, pages = {331-333}, doi = {10.1016/j.cmet.2020.08.003}, pmid = {32877689}, issn = {1932-7420}, mesh = {Adipose Tissue ; Animals ; *Cachexia/etiology ; Growth Differentiation Factor 15 ; Humans ; Mice ; *Neoplasms/complications ; }, abstract = {Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.}, } @article {pmid32876204, year = {2020}, author = {Salim, TR and Andrade, TM and Klein, CH and Oliveira, GMM}, title = {Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.}, journal = {Arquivos brasileiros de cardiologia}, volume = {115}, number = {6}, pages = {1164-1173}, pmid = {32876204}, issn = {1678-4170}, mesh = {Brazil/epidemiology ; *Cardiovascular Diseases ; *Cardiovascular System ; Cause of Death ; Female ; *Heart Defects, Congenital ; Humans ; Male ; Mortality ; }, abstract = {BACKGROUND: Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment.

OBJECTIVES: To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015.

METHODS: A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil.

RESULTS: There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4).

CONCLUSIONS: MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; 115(6):1164-1173).}, } @article {pmid32871469, year = {2020}, author = {Molocea, CE and Tsokanos, FF and Herzig, S}, title = {Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {101-116}, doi = {10.1016/j.coph.2020.07.006}, pmid = {32871469}, issn = {1471-4973}, mesh = {Animals ; Appetite Regulation ; *Cachexia/etiology/immunology/metabolism/therapy ; Humans ; Inflammation Mediators/immunology ; Macrophages/immunology ; *Neoplasms/complications/immunology/metabolism/therapy ; *Obesity/immunology/metabolism/therapy ; }, abstract = {Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.}, } @article {pmid32868877, year = {2020}, author = {Murray, AS and Hyland, TE and Sala-Hamrick, KE and Mackinder, JR and Martin, CE and Tanabe, LM and Varela, FA and List, K}, title = {The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.}, journal = {Oncogene}, volume = {39}, number = {41}, pages = {6421-6436}, pmid = {32868877}, issn = {1476-5594}, support = {R25 GM058905/GM/NIGMS NIH HHS/United States ; F31 CA217148/CA/NCI NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; R01 CA160565/CA/NCI NIH HHS/United States ; R01 CA222359/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use ; Apoptosis/drug effects/genetics ; Breast/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Cell Line, Tumor ; Cell Survival/genetics ; Datasets as Topic ; Disease Progression ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/drug therapy/genetics/*pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*pathology ; }, abstract = {Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.}, } @article {pmid32865471, year = {2021}, author = {Feiss, R and Kostrna, J and Scruggs, JW and Pangelinan, M and Tenenbaum, G}, title = {Effects of music tempo on perceived exertion, attention, affect, heart rate, and performance during isometric strength exercise.}, journal = {Journal of sports sciences}, volume = {39}, number = {2}, pages = {161-169}, doi = {10.1080/02640414.2020.1809974}, pmid = {32865471}, issn = {1466-447X}, mesh = {Adult ; Affect/physiology ; Attention/*physiology ; Exercise/*physiology/*psychology ; Female ; *Heart Rate ; Humans ; Male ; Muscle Strength/physiology ; *Music ; Perception/*physiology ; Physical Exertion/*physiology ; Pleasure/physiology ; Resistance Training/methods ; Young Adult ; }, abstract = {This study examined the effects of slow and fast music tempi on effort-related thoughts, rating of perceived exertion (RPE), affect, heart rate, and performance during isometric strength exercises. Participants were randomly assigned to one of three conditions (no-music control, fast-tempo music, and slow-tempo music) and performed two isometric strength exercises (wall-sit and plank). RPE, attention allocation, and affect were measured during each exercise task. Participants in both the fast- and slow-tempo music conditions maintained a dissociative state for longer than those in the no-music control condition during the wall-sit exercise; however, this effect did not manifest during the plank exercise. Neither music condition influenced HR, RPE, time to volitional exhaustion, or affect. Within the first few minutes of exercise, participants exhibited an increase in HR and perceived exertion, as well as a corresponding shift towards associative attention and a high arousal state. The results are discussed with reference to potential underlying mechanisms and current theories pertaining to RPE, attention allocation, and affect.}, } @article {pmid32862671, year = {2020}, author = {Miller-Ocuin, JL and Howard-McNatt, M and Levine, EA and Chiba, A}, title = {Is Sentinel Lymph Node Biopsy Necessary for Ductal Carcinoma In Situ Patients Undergoing Mastectomy?.}, journal = {The American surgeon}, volume = {86}, number = {8}, pages = {955-957}, doi = {10.1177/0003134820942164}, pmid = {32862671}, issn = {1555-9823}, mesh = {Adult ; Aged ; Axilla ; Biopsy, Large-Core Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mastectomy ; Middle Aged ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; *Unnecessary Procedures ; }, abstract = {BACKGROUND: Current treatment guidelines for ductal carcinoma in situ (DCIS) treated with mastectomy recommend sentinel lymph node biopsy (SLNB). In the modern era, there is a trend toward minimizing invasive staging and treatment of the axilla. In this study, we seek to determine the role of SLNB in patients undergoing mastectomy for the treatment of DCIS.

METHODS: Patients undergoing mastectomy were identified from our institution's SLNB database from 2012 to 2016. Patients were included if core needle biopsy demonstrated DCIS. Patient demographics, tumor characteristics, and pathologic variables were abstracted.

RESULTS: Of 187 patients undergoing mastectomy with SLNB from 2012 to 2016 for DCIS or invasive ductal carcinoma, 39 (21%) were diagnosed with DCIS on core biopsy. Mean age was 57 years. 70% were Caucasian, 18% were African American, 8% were Asian, and the remaining 5% were unknown. One patient (3%) had positive nodes on SLNB and underwent axillary lymph node dissection. Of those with DCIS on core biopsy, 14 (36%) were upstaged to invasive disease on final surgical pathology, including the patient with positive SLNB. Of the remaining 25 (64%) patients with DCIS on final pathology, 0 (0%) had SLNB positivity.

CONCLUSION: Only 3% of patients with DCIS undergoing mastectomy were found to have SLN metastases. However, a significant number of patients (36%) were upstaged due to invasive cancer. Although limited by a small sample size, our results suggest that SLNB should still be recommended to patients undergoing mastectomy for DCIS on core needle biopsy due to the high rate of upstage rate to invasive disease.}, } @article {pmid32862372, year = {2021}, author = {Imamura, T and Yamamoto, Y and Sugiura, T and Okamura, Y and Ito, T and Ashida, R and Ohgi, K and Uesaka, K}, title = {Reconsidering the Optimal Regional Lymph Node Station According to Tumor Location for Pancreatic Cancer.}, journal = {Annals of surgical oncology}, volume = {28}, number = {3}, pages = {1602-1611}, pmid = {32862372}, issn = {1534-4681}, mesh = {Humans ; Lymph Node Excision ; Lymph Nodes/surgery ; Lymphatic Metastasis ; *Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/surgery ; }, abstract = {BACKGROUND: A consensus regarding the optimal extent of lymph node dissection for pancreatic cancer has not yet been achieved. The purpose of this study was to evaluate the efficacy of lymph node dissection according to the location for pancreatic cancer.

METHODS: A total of 495 patients diagnosed with invasive ductal carcinoma of the pancreas who had undergone a pancreatectomy between October 2002 and December 2015 were analyzed. The efficacy index (EI) was calculated for each lymph node station via multiplication of the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to that station.

RESULTS: For pancreatic head (Ph) tumors, mesocolon lymph nodes had a high EI, although not regional. For pancreatic body (Pb) tumors, peri-Ph lymph nodes had a high EI, although not regional. For pancreatic tail (Pt) tumors, lymph nodes along the celiac axis and common hepatic artery had a zero EI, although regional. When the Ph was segmented into the pancreatic neck (Ph-neck), uncinate process (Ph-up), and periampullary regions, hepatoduodenal ligament lymph nodes had a zero EI for Ph-up, although regional; the mesojejunum lymph node also had a zero EI, even for Ph-up, regardless of a high incidence of metastasis. Regarding lymph node recurrence after surgery, recurrence was most frequently found at the peri-Ph lymph node (12%) in patients with Pb tumors who had undergone a distal pancreatectomy.

CONCLUSIONS: The optimal extent of lymph node dissection should be estimated in regard to the tumor location.}, } @article {pmid32858489, year = {2020}, author = {Picillo, M and Amboni, M and Bruni, A and Maletta, R and Barone, P}, title = {Prevalence of heterozygous mutations in Niemann-Pick type C genes in a cohort of progressive supranuclear palsy.}, journal = {Parkinsonism & related disorders}, volume = {79}, number = {}, pages = {9-10}, doi = {10.1016/j.parkreldis.2020.08.013}, pmid = {32858489}, issn = {1873-5126}, mesh = {Heterozygote ; Humans ; Mutation ; *Niemann-Pick Disease, Type C ; Prevalence ; *Supranuclear Palsy, Progressive ; }, } @article {pmid32856854, year = {2020}, author = {Chowdhury, SS and Khatun, M and Khan, TH and Laila, AB}, title = {Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {8}, pages = {2265-2270}, pmid = {32856854}, issn = {2476-762X}, mesh = {Adult ; BRCA1 Protein/*genetics ; Bangladesh/epidemiology ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cross-Sectional Studies ; *Exons ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Tertiary Care Centers ; }, abstract = {BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.

METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.

RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.

CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.}, } @article {pmid32854582, year = {2021}, author = {Weedon-Fekjær, H and Li, X and Lee, S}, title = {Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data.}, journal = {Journal of medical screening}, volume = {28}, number = {3}, pages = {302-310}, doi = {10.1177/0969141320945736}, pmid = {32854582}, issn = {1475-5793}, support = {U01 CA199218/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/diagnosis/epidemiology ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Mass Screening ; }, abstract = {OBJECTIVES: In addition to invasive breast cancer, mammography screening often detects preinvasive ductal carcinoma in situ (DCIS) lesions. The natural progression of DCIS is largely unknown, leading to uncertainty regarding treatment. The natural history of invasive breast cancer has been studied using screening data. DCIS modeling is more complicated because lesions might progress to clinical DCIS, preclinical invasive cancer, or may also regress to a state undetectable by screening. We have here developed a Markov model for DCIS progression, building on the established invasive breast cancer model.

METHODS: We present formulas for the probability of DCIS detection by time since last screening under a Markov model of DCIS progression. Progression rates were estimated by maximum likelihood estimation using BreastScreen Norway data from 1995-2002 for 336,533 women (including 399 DCIS cases) aged 50-69. As DCIS incidence varies by age, county, and mammography modality (digital vs. analog film), a Poisson regression approach was used to align the input data.

RESULTS: Estimated mean sojourn time in preclinical, screening-detectable DCIS phase was 3.1 years (95% confidence interval: 1.3, 7.6) with a screening sensitivity of 60% (95% confidence interval: 32%, 93%). No DCIS was estimated to be non-progressive.

CONCLUSION: Most preclinical DCIS lesions progress or regress with a moderate sojourn time in the screening-detectable phase. While DCIS mean sojourn time could be deduced from DCIS data, any estimate of preclinical DCIS progressing to invasive breast cancer must include data on invasive cancers to avoid strong, probably unrealistic, assumptions.}, } @article {pmid32853021, year = {2021}, author = {Bakhtari, N and Mozdarani, H and Salimi, M and Omranipour, R}, title = {Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.}, journal = {Neoplasma}, volume = {68}, number = {1}, pages = {190-199}, doi = {10.4149/neo_2020_200225N185}, pmid = {32853021}, issn = {0028-2685}, mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/blood/genetics/radiotherapy ; Female ; Humans ; Leukocytes, Mononuclear/metabolism ; *MicroRNAs/biosynthesis/blood ; Middle Aged ; ROC Curve ; Radiation Tolerance ; }, abstract = {Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47±9.93) and 30 healthy women (mean age: 44.43±6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p<0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mirR-22 might be a potential biomarker for the prediction of CR in BC patients.}, } @article {pmid32846803, year = {2020}, author = {Li, G and Yao, J and Wu, T and Chen, Y and Wang, Z and Wang, Y and Wang, F and Zhong, R and Yang, S}, title = {Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.}, journal = {Medicine}, volume = {99}, number = {34}, pages = {e21764}, pmid = {32846803}, issn = {1536-5964}, mesh = {Aged ; Breast Neoplasms/*complications/pathology/therapy ; Colonic Neoplasms/*complications ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; Uterine Neoplasms/*complications ; }, abstract = {RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.

PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.

DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.

OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.

LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.}, } @article {pmid32842718, year = {2020}, author = {An, JK and Woo, JJ and Kwak, HY}, title = {The 8-Year Management of an Older Breast Cancer Patient by Non-surgical Primary Therapies and Minimized Surgery: A Case Report.}, journal = {Annals of geriatric medicine and research}, volume = {24}, number = {3}, pages = {218-222}, doi = {10.4235/agmr.20.0026}, pmid = {32842718}, issn = {2508-4909}, abstract = {A 74-year-old woman presented with a palpable lesion in her right breast. At the time of her visit, she was taking medications for diabetes, hypertension, tremors, tinnitus, and lumbago. She was also caring for her husband, who had dementia. Imaging studies revealed another lesion in addition to the palpable mass. A core biopsy of the palpable mass confirmed invasive ductal carcinoma. Surgery was recommended to remove both masses. However, the patient refused the operation due to her comorbidities and her husband's nursing needs. A modified treatment process, including non-surgical primary therapies, minimized surgery, and close follow-up, for 8 years proved successful. This report focuses on the points to consider in the treatment and management of older patients with breast cancer.}, } @article {pmid32834867, year = {2020}, author = {Tuchner, T and Gilboa-Freedman, G}, title = {Bullshit in a network structure: the two-sided influence of self-generated signals.}, journal = {Social network analysis and mining}, volume = {10}, number = {1}, pages = {65}, pmid = {32834867}, issn = {1869-5450}, abstract = {In today's social network age, information flowing in networks does not derive solely from external sources; people in the network also independently generate signals. These self-generated signals may not be deliberate lies, but they may not bear any relationship with the truth, either. Following the philosopher Harry G. Frankfurt, we refer to such self-generated signals as bullshit. We present an information diffusion model that allows nodes which hold no value to spread information, capturing the diffusion of bullshit information. The presence of self-generated signals (i.e., bullshit) increases the amount of information available for transmission in the network. However, participants in the spread process respond to the existence of such self-generated information by receiving data from internal sources with caution. These two contradictory forces-the increase in information transmission on the one hand, and in suspicion on the other-result in a two-sided effect of bullshit on the total spread time. We first take a numerical approach, simulating our model on Watts-Strogatz networks and building a decision tree to characterize the effects of bullshit given different network structures. We find that increasing the rate of self-generated information may have either a monotonic or non-monotonic effect on the rumor spread time, depending on the network structure and rate of non-self-generated internal communications. Then, taking an analytical approach, we analyze the spread behavior for cliques, and identify the conditions for monotonic behavior in a 2-clique network.}, } @article {pmid32833091, year = {2020}, author = {Shinden, Y and Saho, H and Nomoto, Y and Nagata, A and Minami, K and Nakajo, A and Akahane, T and Hiraki, T and Tanimoto, A and Owaki, T and Kijima, Y and Natsugoe, S}, title = {Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {215}, pmid = {32833091}, issn = {2198-7793}, abstract = {BACKGROUND: When diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty.

CASE PRESENTATION: A 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components.

CONCLUSION: Herein we report a genetically proven contralateral breast metastasis with some intraductal components.}, } @article {pmid32831621, year = {2019}, author = {Kozbial, A and Bhandary, L and Murthy, SK}, title = {Effect of Monocyte Seeding Density on Dendritic Cell Generation in an Automated Perfusion-Based Culture System.}, journal = {Biochemical engineering journal}, volume = {150}, number = {}, pages = {}, pmid = {32831621}, issn = {1369-703X}, support = {U24 AI118665/AI/NIAID NIH HHS/United States ; }, abstract = {Dendritic cells (DCs) are increasingly important for research and clinical use but obtaining sufficient numbers of dendritic cells is a growing challenge. We systemically investigated the effect of monocyte (MO) seeding density on the generation of monocyte-derived immature DCs (iDCs) in MicroDEN, a perfusion-based culture system, as well as 6-well plates. Cell surface markers and the ability of the iDCs to induce proliferation of allogeneic T cells were examined. The data shows a strong relationship between iDC phenotype, specifically CD80/83/86 expression, and T cell proliferation. MicroDEN generated iDCs proved better than well plate generated iDCs at inducing T cell proliferation within the 200k-600k MO/cm[2] seeding density range studied. We attribute this to perfusion in MicroDEN which supplies fresh differentiation medium continuously to the differentiating MOs while concurrently removing depleted medium and toxic byproducts of cellular respiration. MicroDEN generated fewer iDCs on a normalized basis than the well plates at lower MO seeding densities but generated equivalent numbers of iDCs at 600k MO seeding density. These results demonstrate that MicroDEN is capable of generating greater numbers of iDCs with less manual work than standard well plate culture and the MicroDEN generated iDCs have greater ability to induce T cell proliferation.}, } @article {pmid32821874, year = {2020}, author = {Santos, CS and Leite, A and Vinhas, S and Ferreira, S and Moniz, T and Vasconcelos, MW and Rangel, M}, title = {A combined physiological and biophysical approach to understand the ligand-dependent efficiency of 3-hydroxy-4-pyridinone Fe-chelates.}, journal = {Plant direct}, volume = {4}, number = {8}, pages = {e00256}, pmid = {32821874}, issn = {2475-4455}, abstract = {UNLABELLED: Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) class were considered eligible to formulate new Fe fertilizers for Iron Deficiency Chlorosis (IDC). Soybean (Glycine max L.) plants grown in hydroponic conditions and supplemented with Fe-chelate [Fe(mpp)3] were significantly greener, had increased biomass, and were able to translocate more iron from the roots to the shoots than those supplemented with an equal amount of the commercially available chelate [FeEDDHA]. To understand the influence of the structure of 3,4-HPO ligand on the role of the Fe-chelate to improve Fe-uptake, we investigated and report here the effect of Fe-chelates ([Fe(mpp)3], [Fe(dmpp)3], and [Fe(etpp)3]) in addressing IDC. Chlorosis development was assessed by measurement of morphological parameters, quantification of chlorophyll and Fe, and other micronutrient contents, as well as measurement of enzymatic activity (FCR) and gene expression (FRO2, IRT1, and Ferritin). All [Fe(3,4-HPO)3] chelates were able to provide Fe to plants and prevent IDC but with a different efficiency depending on the ligand. We hypothesize that this may be related with the distinct physicochemical characteristics of ligands and complexes, namely, the diverse hydrophilic-lipophilic balance of the three chelates. To test the hypothesis, we performed an EPR biophysical study using liposomes prepared from a soybean (Glycine3 max L.) lipid extract and spin probes. The results showed that the most effective chelate [Fe(mpp)3] shows a preferential location close to the surface while the others prefer the hydrophobic region inside the bilayer.

SIGNIFICANCE STATEMENT: The 3-hydroxy-4-pyridinone Fe-chelates, [Fe(mpp)3], [Fe(dmpp)3], and [Fe(etpp)3], were all able to provide Fe to plants and prevent IDC. Efficacy is dependent on the structure of the ligand. From an EPR biophysical study using spin probes and liposomes, prepared from a soybean lipid extract, we hypothesize that this may be related with the distinct preferential location close to the surface or on the hydrophobic region of the lipid bilayer. [Fe(mpp)3] provide higher amounts of Fe in the leaves.}, } @article {pmid32816842, year = {2020}, author = {Vaidya, JS and Bulsara, M and Baum, M and Wenz, F and Massarut, S and Pigorsch, S and Alvarado, M and Douek, M and Saunders, C and Flyger, HL and Eiermann, W and Brew-Graves, C and Williams, NR and Potyka, I and Roberts, N and Bernstein, M and Brown, D and Sperk, E and Laws, S and Sütterlin, M and Corica, T and Lundgren, S and Holmes, D and Vinante, L and Bozza, F and Pazos, M and Le Blanc-Onfroy, M and Gruber, G and Polkowski, W and Dedes, KJ and Niewald, M and Blohmer, J and McCready, D and Hoefer, R and Kelemen, P and Petralia, G and Falzon, M and Joseph, DJ and Tobias, JS}, title = {Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m2836}, pmid = {32816842}, issn = {1756-1833}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; 14/49/13/DH_/Department of Health/United Kingdom ; HTA/14/49/13/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Radiotherapy Dosage ; Survival Rate ; }, abstract = {OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).

MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.

RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).

CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.

TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.}, } @article {pmid32816400, year = {2020}, author = {Ceh, SM and Annerer-Walcher, S and Körner, C and Rominger, C and Kober, SE and Fink, A and Benedek, M}, title = {Neurophysiological indicators of internal attention: An electroencephalography-eye-tracking coregistration study.}, journal = {Brain and behavior}, volume = {10}, number = {10}, pages = {e01790}, pmid = {32816400}, issn = {2162-3279}, support = {P 29801/FWF_/Austrian Science Fund FWF/Austria ; P29801-B27//Austrian Science Fund/ ; }, mesh = {*Attention ; Cognition ; Electroencephalography ; *Eye-Tracking Technology ; Neurophysiology ; }, abstract = {INTRODUCTION: Many goal-directed and spontaneous everyday activities (e.g., planning, mind wandering) rely on an internal focus of attention. Internally directed cognition (IDC) was shown to differ from externally directed cognition in a range of neurophysiological indicators such as electroencephalogram (EEG) alpha activity and eye behavior.

METHODS: In this EEG-eye-tracking coregistration study, we investigated effects of attention direction on EEG alpha activity and various relevant eye parameters. We used an established paradigm to manipulate internal attention demands in the visual domain within tasks by means of conditional stimulus masking.

RESULTS: Consistent with previous research, IDC involved relatively higher EEG alpha activity (lower alpha desynchronization) at posterior cortical sites. Moreover, IDC was characterized by greater pupil diameter (PD), fewer microsaccades, fixations, and saccades. These findings show that internal versus external cognition is associated with robust differences in several indicators at the neural and perceptual level. In a second line of analysis, we explored the intrinsic temporal covariation between EEG alpha activity and eye parameters during rest. This analysis revealed a positive correlation of EEG alpha power with PD especially in bilateral parieto-occipital regions.

CONCLUSION: Together, these findings suggest that EEG alpha activity and PD represent time-sensitive indicators of internal attention demands, which may be involved in a neurophysiological gating mechanism serving to shield internal cognition from irrelevant sensory information.}, } @article {pmid32815708, year = {2020}, author = {Wong, HC and Wang, Q and Speller, EM and Li, Z and Cabral, JT and Low, HY}, title = {Photoswitchable Solubility of Fullerene-Doped Polymer Thin Films.}, journal = {ACS nano}, volume = {14}, number = {9}, pages = {11352-11362}, doi = {10.1021/acsnano.0c03450}, pmid = {32815708}, issn = {1936-086X}, abstract = {Controlling polymer film solubility is of fundamental and practical interest and is typically achieved by synthetically modifying the polymer structure to insert reactive groups. Here, we demonstrate that the addition of fullerenes or its derivatives (C60 or phenyl-C61-butyric acid methyl ester, PCBM) to polymers, followed by ultraviolet (UV) illumination can change the film solubility. Contrary to most synthetic polymers, which dissolve in organic solvents but not in water, the fullerene-doped polymer films (such as polystyrene) can dissolve in water yet remain stable in organic solvents. This photoswitchable solubility effect is not observed in either film constituents individually and is derived from a synergy of photochemistries. First, polymer photooxidation generates macroradicals which cross-link with radical-scavenging PCBM, thereby contributing to the films' insolubility in organic solvents. Second, light exposure enhances polymer photooxidation in the presence of PCBM via the singlet oxygen pathway. This results in polymer backbone scission and formation of photooxidized products which can form hydrogen bonds with water, both contributing to water solubility. Nevertheless, the illuminated doped polymer thin films are mechanically robust, exhibiting significantly increased modulus and density compared to their pristine counterpart, such that they can remain intact even upon sonication in conventional organic solvents. We further demonstrate the application of this solubility-switching effect in dual tone photolithography, via a facile, economical, and environmentally benign solution-processing route made possible by the photoactive nature of polymer-PCBM thin films.}, } @article {pmid32815034, year = {2021}, author = {van der Slot, MA and Hollemans, E and den Bakker, MA and Hoedemaeker, R and Kliffen, M and Budel, LM and Goemaere, NNT and van Leenders, GJLH}, title = {Inter-observer variability of cribriform architecture and percent Gleason pattern 4 in prostate cancer: relation to clinical outcome.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {478}, number = {2}, pages = {249-256}, pmid = {32815034}, issn = {1432-2307}, mesh = {Aged ; Carcinoma/*pathology/surgery ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Observer Variation ; Predictive Value of Tests ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Reproducibility of Results ; Treatment Outcome ; Tumor Burden ; }, abstract = {The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3-119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0-25%, 26-50%, 51-75% and 76-100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff's α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.}, } @article {pmid32812198, year = {2021}, author = {Zhao, H}, title = {The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {28}, number = {1}, pages = {187-195}, pmid = {32812198}, issn = {1880-4233}, mesh = {Aged ; Biomarkers, Tumor/analysis/metabolism ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*mortality/pathology/therapy ; Carcinoma, Lobular/diagnosis/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/statistics & numerical data ; Clinical Decision-Making ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy/methods/statistics & numerical data ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Complex and Mixed/diagnosis/*mortality/pathology/therapy ; Prognosis ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Retrospective Studies ; SEER Program/statistics & numerical data ; }, abstract = {BACKGROUND: To investigate the prognosis of females with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) according to hormone receptor (HR) and HER2 status.

METHODS: Data of 171,881 patients from the SEER database were analyzed. Propensity score matching was used to balance the covariates. Breast cancer-specific survival (BCSS) and overall survival (OS) of IDC, ILC, and IDLC were investigated.

RESULTS: Patients with ILC were older, had lower tumor grade, higher tumor stage, larger tumor size, more nodal metastasis, higher estrogen receptor(+), lower HER2(-), and less likely to receive partial mastectomy and chemotherapy compared with IDC and IDLC. ILC and IDLC showed better prognosis than IDC after matching by Kaplan-Meier curves. Multivariate Cox regression showed better OS of ILC and IDLC compared with IDC with hazard ratio and a 95% confidence interval of 0.84 (0.77-0.90) and 0.91 (0.83-1.00), respectively. For HR(+)HER2(-) subgroup, ILC showed better OS than IDC; IDC showed worse BCSS and OS than IDLC. For HR(+)HER2(+); ILC showed better OS compared with IDLC; there were no survival differences of IDC, ILC, and IDLC for HER2(+). For HR(-)HER2(-), ILC and IDC showed better BCSS and OS compared with IDLC by multivariate analysis.

CONCLUSIONS: The prognoses of female patients with IDC, ILC or IDLC were associated with the molecular subtypes of breast carcinoma. Management decisions should be based on pathological types and molecular subtypes.}, } @article {pmid32811533, year = {2020}, author = {Chao, X and Liu, L and Sun, P and Yang, X and Li, M and Luo, R and Huang, Y and He, J and Yun, J}, title = {Immune parameters associated with survival in metaplastic breast cancer.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {92}, pmid = {32811533}, issn = {1465-542X}, mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*immunology/metabolism ; Biomarkers, Tumor/*immunology/metabolism ; Breast Neoplasms/*immunology/*mortality/pathology/therapy ; CD8-Positive T-Lymphocytes/*immunology ; Carcinoma, Squamous Cell/immunology/mortality/pathology/therapy ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Programmed Cell Death 1 Receptor/*immunology/metabolism ; Survival Rate ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.

METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm[2]) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm[2]), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.

RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm[2], 20%), CD4+ TILs (> 250/mm[2]), and CD8+ TILs (> 70/mm[2]) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.

CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.}, } @article {pmid32797262, year = {2021}, author = {Makary, J and Phan, K and McClintock, G and Doctor, M and Habashy, D and Heywood, S and McCombie, SP and Arianayagam, M and Canagasingham, B and Ferguson, R and Goolam, A and Khadra, M and Ko, R and Varol, C and Winter, M and Roberts, MJ}, title = {Bladder infusion versus standard catheter removal for trial of void: a systematic review and meta-analysis.}, journal = {World journal of urology}, volume = {39}, number = {6}, pages = {1781-1788}, pmid = {32797262}, issn = {1433-8726}, mesh = {*Catheters, Indwelling ; *Device Removal ; Humans ; Urinary Bladder ; *Urinary Catheters ; Urinary Retention/*therapy ; *Urination ; }, abstract = {PURPOSE: To compare the efficacy and time-to-discharge of two methods of trial of void (TOV): bladder infusion versus standard catheter removal.

METHODS: Electronic searches for randomized controlled trials (RCTs) comparing bladder infusion versus standard catheter removal were performed using multiple electronic databases from dates of inception to June 2020. Participants underwent TOV after acute urinary retention or postoperatively after intraoperative indwelling catheter (IDC) placement. Quality assessment and meta-analyses were performed, with odds ratio and mean time difference used as the outcome measures.

RESULTS: Eight studies, comprising 977 patients, were included in the final analysis. Pooled meta-analysis demonstrated that successful TOV was significantly higher in the bladder infusion group compared to standard TOV (OR 2.41, 95% CI 1.53-3.8, p = 0.0005), without significant heterogeneity (I[2]=19%). The bladder infusion group had a significantly shorter time-to-decision in comparison to standard TOV (weighted mean difference (WMD)-148.96 min, 95% CI - 242.29, - 55.63, p = 0.002) and shorter time-to-discharge (WMD - 89.68 min, 95% CI - 160.55, - 18.88, p = 0.01). There was no significant difference in complication rates between the two groups.

CONCLUSION: The bladder infusion technique of TOV may be associated with a significantly increased likelihood of successful TOV and reduced time to discharge compared to standard TOV practices.}, } @article {pmid32797086, year = {2020}, author = {Grosset, AA and Dallaire, F and Nguyen, T and Birlea, M and Wong, J and Daoust, F and Roy, N and Kougioumoutzakis, A and Azzi, F and Aubertin, K and Kadoury, S and Latour, M and Albadine, R and Prendeville, S and Boutros, P and Fraser, M and Bristow, RG and van der Kwast, T and Orain, M and Brisson, H and Benzerdjeb, N and Hovington, H and Bergeron, A and Fradet, Y and Têtu, B and Saad, F and Leblond, F and Trudel, D}, title = {Identification of intraductal carcinoma of the prostate on tissue specimens using Raman micro-spectroscopy: A diagnostic accuracy case-control study with multicohort validation.}, journal = {PLoS medicine}, volume = {17}, number = {8}, pages = {e1003281}, pmid = {32797086}, issn = {1549-1676}, support = {P50 CA211015/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Aged ; Canada/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/epidemiology/pathology ; Case-Control Studies ; Cohort Studies ; Humans ; Machine Learning/*standards ; Male ; Middle Aged ; Nonlinear Optical Microscopy/methods/*standards ; Prostatic Neoplasms/*diagnostic imaging/epidemiology/pathology ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {BACKGROUND: Prostate cancer (PC) is the most frequently diagnosed cancer in North American men. Pathologists are in critical need of accurate biomarkers to characterize PC, particularly to confirm the presence of intraductal carcinoma of the prostate (IDC-P), an aggressive histopathological variant for which therapeutic options are now available. Our aim was to identify IDC-P with Raman micro-spectroscopy (RμS) and machine learning technology following a protocol suitable for routine clinical histopathology laboratories.

METHODS AND FINDINGS: We used RμS to differentiate IDC-P from PC, as well as PC and IDC-P from benign tissue on formalin-fixed paraffin-embedded first-line radical prostatectomy specimens (embedded in tissue microarrays [TMAs]) from 483 patients treated in 3 Canadian institutions between 1993 and 2013. The main measures were the presence or absence of IDC-P and of PC, regardless of the clinical outcomes. The median age at radical prostatectomy was 62 years. Most of the specimens from the first cohort (Centre hospitalier de l'Université de Montréal) were of Gleason score 3 + 3 = 6 (51%) while most of the specimens from the 2 other cohorts (University Health Network and Centre hospitalier universitaire de Québec-Université Laval) were of Gleason score 3 + 4 = 7 (51% and 52%, respectively). Most of the 483 patients were pT2 stage (44%-69%), and pT3a (22%-49%) was more frequent than pT3b (9%-12%). To investigate the prostate tissue of each patient, 2 consecutive sections of each TMA block were cut. The first section was transferred onto a glass slide to perform immunohistochemistry with H&E counterstaining for cell identification. The second section was placed on an aluminum slide, dewaxed, and then used to acquire an average of 7 Raman spectra per specimen (between 4 and 24 Raman spectra, 4 acquisitions/TMA core). Raman spectra of each cell type were then analyzed to retrieve tissue-specific molecular information and to generate classification models using machine learning technology. Models were trained and cross-validated using data from 1 institution. Accuracy, sensitivity, and specificity were 87% ± 5%, 86% ± 6%, and 89% ± 8%, respectively, to differentiate PC from benign tissue, and 95% ± 2%, 96% ± 4%, and 94% ± 2%, respectively, to differentiate IDC-P from PC. The trained models were then tested on Raman spectra from 2 independent institutions, reaching accuracies, sensitivities, and specificities of 84% and 86%, 84% and 87%, and 81% and 82%, respectively, to diagnose PC, and of 85% and 91%, 85% and 88%, and 86% and 93%, respectively, for the identification of IDC-P. IDC-P could further be differentiated from high-grade prostatic intraepithelial neoplasia (HGPIN), a pre-malignant intraductal proliferation that can be mistaken as IDC-P, with accuracies, sensitivities, and specificities > 95% in both training and testing cohorts. As we used stringent criteria to diagnose IDC-P, the main limitation of our study is the exclusion of borderline, difficult-to-classify lesions from our datasets.

CONCLUSIONS: In this study, we developed classification models for the analysis of RμS data to differentiate IDC-P, PC, and benign tissue, including HGPIN. RμS could be a next-generation histopathological technique used to reinforce the identification of high-risk PC patients and lead to more precise diagnosis of IDC-P.}, } @article {pmid32795725, year = {2020}, author = {Fleury, EFC and Marcomini, K}, title = {Impact of radiomics on the breast ultrasound radiologist's clinical practice: From lumpologist to data wrangler.}, journal = {European journal of radiology}, volume = {131}, number = {}, pages = {109197}, doi = {10.1016/j.ejrad.2020.109197}, pmid = {32795725}, issn = {1872-7727}, mesh = {*Artificial Intelligence ; Biopsy ; Breast/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Fibroadenoma/diagnostic imaging/pathology ; Humans ; Phyllodes Tumor/diagnostic imaging/pathology ; Physician's Role ; ROC Curve ; *Radiologists ; Sensitivity and Specificity ; *Software ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: The study aims to assess the impact of radiomics in the clinical practice of breast ultrasound, to determine which lesions are undetermined by the software, and to discuss the future of the radiologist's role.

METHODS: Consecutive analyses of 207 ultrasound masses from January 2018 to April 2019 referred for percutaneous breast biopsy. Breast masses were classified using dedicated ultrasound software (AI). The AI software automatically classified the masses on a scale of 0-100, where 100 is the most suspicious. We adopt the histology results as the gold standard. The cut-off point of malignancy by radiomics was determined, with ±10 % of margin error according to the Youden's index. We considered these lesions as undetermined masses. The performance of the AI software and the radiologist classification was compared using the area under roc curves (AUROC). We also discuss the impact of radiologist validation of AI results, especially in undetermined lesions.

RESULTS: Of the 207 evaluated masses, 143 were benign, and 64 were malignant. The Youden's index was 0.516, including undetermined masses with a varied range of 10 % (0.464-0.567). Twenty-one (14.58 %) benign and twelve (19.05 %) malignant masses were in this range. The best accuracy performance to classify masses was the combination of the reader and AI (0.829). The most common undetermined masses in AI were fibroadenoma, followed by phyllodes tumor, steatonecrosis as benign. Whereas, low-grade, and high-grade invasive ductal carcinoma represents the malignant lesions.

CONCLUSIONS: Artificial Intelligence has a reliable performance in ultrasound breast masses classification. Radiologist validation is critical to determine the final BI-RADS assessment, especially in undetermined masses to obtain the best classification performance.}, } @article {pmid32792796, year = {2020}, author = {Chikkannaiah, P and Thangngeo, D and Guruprasad, C and Venkataramanappa, S}, title = {Clinicopathological Study of Mucinous Carcinoma of Breast with Emphasis on Cytological Features: A Study at Tertiary Care Teaching Hospital of South India.}, journal = {Journal of laboratory physicians}, volume = {12}, number = {1}, pages = {68-75}, pmid = {32792796}, issn = {0974-2727}, abstract = {Introduction Mucinous carcinoma (MC) is a rare form of breast cancer. It accounts for 1 to 7% of the cases and characterized by the presence of extracellular mucin (ECM). Depending on the amount of mucin, it is classified into pure mucinous carcinoma (> 90%, PMC) and mixed mucinous carcinoma (MMC; < 90%). In comparison to most common subtypes, MC is having better prognosis. There exist clinicopathological differences among PMC and MMC and also MC and IDC-NOS. Materials and Methods MCs diagnosed between January 2012 and December 2017 were included. Fine needle aspiration cytology smears were screened for cellularity, ECM, nuclear pleomorphism, signet ring cells (SRC), mucinophages, and myxovascular fragments (MVF). Histopathology slides were screened to confirm the diagnosis. Immunohistochemistry slides were graded as per the standard protocol. Statistical analyses were performed by SPSS software. Results In the present study, MC constituted 3.3%. The mean age of the patients was 50.9 years. ECM, mucinophages, and SRC were the key diagnostic cytological features. The PMC and MMC were clinicopathologically distinct with respect to gross findings and lymph node status. MMCs were highly proliferative. The mean duration of follow-up was 24.5 months. Complications were more common in MMC than PMC. Lymph node involvement is the key prognostic factor and it is independent of other prognostic factors like age, size, and hormonal receptor status. Conclusion PMC are rare subtype of breast cancer. The diagnostic cytological features are ECM, MVF, and SRC. MMC and PMC are clinicopathologically and genetically distinct.}, } @article {pmid32791433, year = {2021}, author = {Rais, S and Islam, A and Ahmad, I and Kumar, S and Chauhan, A and Javed, H}, title = {Preparation of a new magnetic ion-imprinted polymer and optimization using Box-Behnken design for selective removal and determination of Cu(II) in food and wastewater samples.}, journal = {Food chemistry}, volume = {334}, number = {}, pages = {127563}, doi = {10.1016/j.foodchem.2020.127563}, pmid = {32791433}, issn = {1873-7072}, mesh = {Adsorption ; Allyl Compounds/chemistry ; Copper/*analysis/isolation & purification ; Dicarboxylic Acids/chemistry ; Food Analysis/instrumentation/*methods ; Food Contamination/analysis ; Imidazoles/chemistry ; Limit of Detection ; Magnetic Phenomena ; Molecular Imprinting/*methods ; Polymers/*chemistry ; Wastewater/analysis ; Water Pollutants, Chemical/*analysis/isolation & purification ; }, abstract = {A new magnetic Cu(II) IIP (Fe3O4@IIP-IDC) is synthesized by polymerization of Imidazole-4,5-dicarboxylic acid functionalized Allyl chloride, and significant improvement of its performance has been compared. SPE parameters were optimized using Box-Behnken design to achieve the twin objectives of quantitative determination and removal of Cu(II). FLPSO kinetic model and BS isotherm model fits well with the capacity of 175 mg g[-1]. Analytical figures of merit includes a linearity range of 10-5,000 µg L[-1] (R[2] = 0.9986), preconcentration factor of 50 after eluting with 5 mL of 1 M HNO3, LOD of 1.03 µg L[-1] and LOQ of 4.5 µg L[-1]. Accuracy was assessed by analysis of SRM (Standard Reference Material) and recovery experiments after spiking in food samples (Tea, coffee, chocolate, spinach, infant milk substitute) and battery wastewater. Ease of use, reusability (15 cycles), rapid adsorption and high selectivity makes it a promising candidate for efficient and selective removal and trace determination.}, } @article {pmid32790473, year = {2021}, author = {Shuman, E and Saguy, T and van Zomeren, M and Halperin, E}, title = {Disrupting the system constructively: Testing the effectiveness of nonnormative nonviolent collective action.}, journal = {Journal of personality and social psychology}, volume = {121}, number = {4}, pages = {819-841}, doi = {10.1037/pspi0000333}, pmid = {32790473}, issn = {1939-1315}, support = {//Ruderman Family Foundation/ ; //Arison Foundation/ ; }, mesh = {Aggression ; Humans ; Intention ; *Motivation ; *Social Change ; Vulnerable Populations ; }, abstract = {Collective action research tends to focus on motivations of the disadvantaged group, rather than on which tactics are effective at driving the advantaged group to make concessions to the disadvantaged. We focused on the potential of nonnormative nonviolent action as a tactic to generate support for concessions among advantaged group members who are resistant to social change. We propose that this tactic, relative to normative nonviolent and to violent action, is particularly effective because it reflects constructive disruption: a delicate balance between disruption (which can put pressure on the advantaged group to respond) and perceived constructive intentions (which can help ensure that the response to action is a conciliatory one). We test these hypotheses across 4 contexts (total N = 3650). Studies 1-3 demonstrate that nonnormative nonviolent action (compared with inaction, normative nonviolent action, and violent action) is uniquely effective at increasing support for concessions to the disadvantaged among resistant advantaged group members (compared with advantaged group members more open to social change). Study 3 shows that constructive disruption mediates this effect. Study 4 shows that perceiving a real-world ongoing protest as constructively disruptive predicts support for the disadvantaged, whereas Study 5 examines these processes longitudinally over 2 months in the context of an ongoing social movement. Taken together, we show that nonnormative nonviolent action can be an effective tactic for generating support for concessions to the disadvantaged among those who are most resistant because it generates constructive disruption. (PsycInfo Database Record (c) 2021 APA, all rights reserved).}, } @article {pmid32789812, year = {2021}, author = {Wakefield, B and Diko, S and Gilmer, R and Connell, KA and DeWitt, PE and Hurt, KJ}, title = {Accuracy of obstetric laceration diagnoses in the electronic medical record.}, journal = {International urogynecology journal}, volume = {32}, number = {7}, pages = {1907-1915}, pmid = {32789812}, issn = {1433-3023}, mesh = {Anal Canal/injuries ; Delivery, Obstetric ; Electronic Health Records ; Female ; Humans ; *Lacerations/diagnosis/epidemiology ; Perineum/injuries ; Pregnancy ; Retrospective Studies ; Risk Factors ; }, abstract = {INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes.

METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs).

RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity = 96%, specificity = 100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p = 0.070) or the IDCs (p = 0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p < 0.05) owing to errors in IDC minor laceration diagnoses.

CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.}, } @article {pmid32789159, year = {2020}, author = {Cochrane, E and Kim, S and Kudelka, A and Burke, W}, title = {Invasive ductal breast carcinoma metastasis to the cervix: A case review and clinical correlation.}, journal = {Gynecologic oncology reports}, volume = {33}, number = {}, pages = {100616}, pmid = {32789159}, issn = {2352-5789}, abstract = {•Metastatic invasive ductal carcinoma.•IDC metastasis to cervix.•Unusual metastasis to cervix.}, } @article {pmid32788081, year = {2021}, author = {Habrawi, Z and Melkus, MW and Khan, S and Henderson, J and Brandi, L and Chu, V and Layeequr Rahman, R}, title = {Cryoablation: A promising non-operative therapy for low-risk breast cancer.}, journal = {American journal of surgery}, volume = {221}, number = {1}, pages = {127-133}, doi = {10.1016/j.amjsurg.2020.07.028}, pmid = {32788081}, issn = {1879-1883}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; *Cryosurgery ; Feasibility Studies ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Risk Assessment ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the feasibility of cryoablation for early-stage low-risk breast cancer without tumor resection.

METHODS: Women diagnosed with ER+, PR+, and HER2-infiltrating ductal carcinomas ≤1.5 cm were treated with cryoablation. The non-surgical procedure used a Visica® 2 Treatment System with ultrasound guidance for ablation of the tumor with a 1 cm margin. Patients were monitored at 6-month intervals by MRI, mammogram, and ultrasound.

RESULTS: Twelve patients with unifocal breast cancer were treated with cryoablation for local control without follow-up tumor resection. All patients received adjuvant endocrine therapy, and none had radiation. The median follow-up was 28.5 (range = 4-41) months with 11 patients having at least one six-month follow-up. All imaging modalities showed complete ablation of target zone 11/11 (100%). Four patients (33.3%) have been followed up for ≥ 2 years with no local failure or residual disease.

CONCLUSION: Cryoablation of early-stage low-risk (ER+, PR+, and HER2-) breast cancer is a safe alternative to surgery.}, } @article {pmid32787871, year = {2020}, author = {Yoon, GY and Choi, WJ and Cha, JH and Shin, HJ and Chae, EY and Kim, HH}, title = {The role of MRI and clinicopathologic features in predicting the invasive component of biopsy-confirmed ductal carcinoma in situ.}, journal = {BMC medical imaging}, volume = {20}, number = {1}, pages = {95}, pmid = {32787871}, issn = {1471-2342}, mesh = {Adult ; Biopsy ; Breast/diagnostic imaging/metabolism/*pathology ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/metabolism ; Logistic Models ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness/*diagnostic imaging/pathology ; Odds Ratio ; Radiographic Image Interpretation, Computer-Assisted ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: The upgrade rate of biopsy-confirmed ductal carcinoma in situ (DCIS) to invasive carcinoma is up to 50% on final pathology. We investigated MRI and clinicopathologic predictors of the invasive components of DCIS diagnosed by preoperative biopsy and then compared MRI features between patients with DCIS, microinvasive ductal carcinoma (mIDC), and invasive ductal carcinoma (IDC) diagnosed on final pathology.

METHODS: Two hundred and one patients with 206 biopsy-confirmed DCIS lesions were enrolled. MRI and clinicopathologic features were used to predict either mIDC or IDC via a cumulative logistic regression analysis. For the lesions detected on MRI, morphologic and kinetic analyses were performed using the Chi-square, Fisher's exact, and Kruskal-Wallis tests.

RESULTS: Of all the lesions, 112 (54.4%) were diagnosed as DCIS, 50 (24.3%) were upgraded to mIDC, and 44 (21.4%) to IDC. The detection on MRI as mass (Odds ratio (OR) = 8.84, 95% confidence interval (CI) = 1.05-74.04, P = 0.045) or non-mass enhancement (NME; OR = 11.17, 95% CI = 1.35-92.36, P = 0.025), negative progesterone receptor (PR; OR = 2.40, 95% CI = 1.29-4.44, P = 0.006), and high Ki-67 level (OR = 2.42, 95% CI = 1.30-4.50, P = 0.005) were significant independent predictors of histologic upgrade. On MRI, 87 (42.2%) lesions appeared as mass and 107 (51.9%) as NME. Irregularly shaped, not-circumscribed, heterogeneous, or rim-enhancing masses with intratumoral high signal intensity or peritumoral edema, clumped or clustered ring-enhancing NMEs, and high peak enhancement were significantly associated with histologic upgrade (P < 0.001).

CONCLUSION: MRI detection, negative PR, and high Ki-67 levels are associated with a histologic upgrade in patients with biopsy-confirmed DCIS. Suspicious MRI features are more frequent in such patients.}, } @article {pmid32785515, year = {2020}, author = {Souza, TO and Souza, ER and Pinto, LW}, title = {Analysis of the correlation of socioeconomic, sanitary, and demographic factors with homicide deaths - Bahia, Brazil, 2013-2015.}, journal = {Revista brasileira de enfermagem}, volume = {73}, number = {6}, pages = {e20190346}, doi = {10.1590/0034-7167-2019-0346}, pmid = {32785515}, issn = {1984-0446}, mesh = {Brazil/epidemiology ; Demography ; Educational Status ; *Homicide ; Humans ; Socioeconomic Factors ; }, abstract = {OBJECTIVE: To analyze the correlation of socioeconomic, sanitary, and demographic factors with homicides in Bahia, from 2013 to 2015.

METHODS: Ecological study, using data from the Information System on Mortality and from the Superintendence of Economic and Social Studies. The depending variable is the corrected homicide rate. Explanatory variables were categorized in four axes. Simple and multiple negative binomial regression models were used.

RESULTS: Positive associations were found between homicides and the Index of Economy and Finances (IEF), the Human Development Index, the Gini Index, population density, and legal intervention death rates (LIDR). The variables Index of Education Levels (IEL), rates of death with undetermined intentions (RDUI), and the proportion of ill-defined causes (IDC) presented a negative association with the homicide rates.

CONCLUSION: The specific features of the context of each community, in addition to broader socioeconomic municipal factors, directly interfere in life conditions and increase the risk of dying by homicide.}, } @article {pmid32783993, year = {2020}, author = {Domínguez-de-la-Cruz, E and Muñoz, ML and Pérez-Muñoz, A and García-Hernández, N and Moctezuma-Meza, C and Hinojosa-Cruz, JC}, title = {Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.}, journal = {Gene}, volume = {761}, number = {}, pages = {145047}, doi = {10.1016/j.gene.2020.145047}, pmid = {32783993}, issn = {1879-0038}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism ; Case-Control Studies ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes/genetics ; Humans ; Mexico/epidemiology ; Middle Aged ; Mitochondria/genetics ; }, abstract = {Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.}, } @article {pmid32782691, year = {2020}, author = {Chen, ML and Ma, ZS and Cao, FL and Yan, XQ and Zhang, LM and Wang, XB and Xie, BJ}, title = {Retroperitoneal metastasis synchronous with brain and mediastinal lymph nodes metastasis from breast invasive ductal carcinoma as the first site of distant metastasis: a case report and review of literature.}, journal = {International journal of clinical and experimental pathology}, volume = {13}, number = {7}, pages = {1693-1697}, pmid = {32782691}, issn = {1936-2625}, abstract = {Breast carcinoma retroperitoneal metastasis is rare. The clinical symptoms of this disease are always non-specific. Laboratory tests are not always helpful for diagnosis and evaluation. We reported a case of a 52 year old Chinese patient who was diagnosed with retroperitoneal metastasis from breast invasive ductal carcinoma as the first site of distant metastasis synchronous with brain and mediastinal lymph nodes metastasis 4 years after modified radical mastectomy. Second-line chemotherapy of docetaxel and capecitabine was recommended. The response evaluation every two to three months was good. Unfortunately, the metastasis in the brain advanced. The patient was transferred to a radiotherapy department to receive radiotherapy and died 10 months later. We also review the related literature.}, } @article {pmid32782569, year = {2020}, author = {Zhao, J and Liu, J and Wu, N and Zhang, H and Zhang, S and Li, L and Wang, M}, title = {ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer.}, journal = {Oncology letters}, volume = {20}, number = {3}, pages = {2499-2505}, pmid = {32782569}, issn = {1792-1074}, abstract = {The aim of the present study was to analyze the expression levels of angiopoietin-like 4 (ANGPTL4) in breast cancer to investigate the association between ANGPTL4 and breast cancer. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues, including 205 invasive ductal carcinoma (IDC) of no special type, 40 normal breast, 40 atypical ductal hyperplasia (ADH) and 40 ductal carcinomas in situ (DCIS) tissues. The non-parametric Kruskal-Wallis test was used to evaluate the differential expression of ANGPTL4 and clinicopathological parameters in breast cancer. Kaplan-Meier analysis and Cox regression analysis were used to evaluate the association between the expression levels of ANGPTL4 and the prognosis of breast cancer. The results revealed that ANGPTL4 expression was higher in IDC (63.4%; 130/205) compared with in normal breast tissues (17.5%; 7/40), ADH (30%; 12/40) and DCIS (37.5%; 15/40). The clinical significance of ANGPTL4 expression was analyzed in a total of 205 IDC tissues, and high expression levels of ANGPTL4 were positively associated with pathological stage (P<0.001), tumor size (P<0.001), histological grade (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P<0.001) and local recurrence (P<0.001). Kaplan-Meier analysis revealed that patients with high ANGPTL4 expression had a shorter overall survival (OS; P<0.001) and disease-free survival (DFS; P<0.001) compared with patients with low ANGPTL4 expression. Multivariate Cox regression analysis revealed that ANGPTL4 was an independent prognostic factor for breast cancer OS (P=0.034) and DFS (P=0.011). The results of the present study demonstrated that ANGPLT4 was associated with malignant progression and poor prognosis of breast cancer, suggesting that ANGPLT4 may be a novel therapeutic target for breast cancer.}, } @article {pmid32782013, year = {2020}, author = {Kurozumi, S and Alsaleem, M and Monteiro, CJ and Bhardwaj, K and Joosten, SEP and Fujii, T and Shirabe, K and Green, AR and Ellis, IO and Rakha, EA and Mongan, NP and Heery, DM and Zwart, W and Oesterreich, S and Johnston, SJ}, title = {Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {85}, pmid = {32782013}, issn = {1465-542X}, support = {AAM127669/WT_/Wellcome Trust/United Kingdom ; SAC160073/KOMEN/Susan G. Komen/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Computer Simulation ; Databases, Genetic/statistics & numerical data ; Female ; Humans ; Middle Aged ; *Mutation ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.

METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.

RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2-11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04-5.05; p = 0.040).

CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.}, } @article {pmid32781417, year = {2020}, author = {Lu, K and Wang, X and Zhang, W and Ye, H and Lao, L and Zhou, X and Yao, S and Lv, F}, title = {Clinicopathological and genomic features of breast mucinous carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {130-137}, pmid = {32781417}, issn = {1532-3080}, mesh = {Adenocarcinoma, Mucinous/*genetics/*pathology ; Adult ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Female ; Gene Expression Profiling ; Genome ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prospective Studies ; SEER Program ; Young Adult ; }, abstract = {INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood.

MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis.

RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P < 0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3.

CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.}, } @article {pmid32776387, year = {2020}, author = {Takahara, T and Satou, A and Sugie, M and Watanabe, M and Kanao, K and Sumitomo, M and Tsuzuki, T}, title = {Prognostic significance of p16 expression in high-grade prostate adenocarcinoma.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {743-751}, doi = {10.1111/pin.12997}, pmid = {32776387}, issn = {1440-1827}, mesh = {Adenocarcinoma/*diagnosis/drug therapy/metabolism/pathology ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/*diagnosis/drug therapy/metabolism/pathology ; }, abstract = {Management of advanced hormone-naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52-87) years. The median follow-up was 62 months (range 2-98). Fourteen patients had p16-positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16-positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC-P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis-targeted therapy.}, } @article {pmid32775251, year = {2020}, author = {Wang, H and Hu, Y and Li, H and Xie, Y and Wang, X and Wan, W}, title = {Preliminary study on identification of estrogen receptor-positive breast cancer subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) texture analysis.}, journal = {Gland surgery}, volume = {9}, number = {3}, pages = {622-628}, pmid = {32775251}, issn = {2227-684X}, support = {U24 EB028980/EB/NIBIB NIH HHS/United States ; }, abstract = {BACKGROUND: Currently, breast cancer is divided into Luminal A, Luminal B, HER-2 overexpression (HER-2) and basal cell at genetic level. However, the differential diagnosis of estrogen receptor (ER)-positive breast cancer subtypes is rare. Therefore, we aimed to investigate the feasibility of identifying the ER-positive breast cancer subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) texture analysis.

METHODS: A retrospective analysis was performed for clinical data of 51 patients with ER-positive breast invasive ductal carcinoma confirmed by surgery and pathology from January 20 to October 2018. FireVoxel texture analysis software was used to delineate the tumor boundary layer by layer. The differences in the above characteristics between Luminal A and Luminal B breast cancer were compared, and the diagnostic efficacy of statistically significant texture parameters for ER-positive breast cancer subtypes was analyzed.

RESULTS: There were no significant differences in mean, standard deviation (SD), skewness and tumor size between Luminal A and Luminal B groups (P>0.05). The kurtosis, inhomogeneity and entropy could effectively distinguish between the two groups with statistically significant difference (P=0.001, P=0.000, and P=0.000). The area under the receiver operating characteristic (ROC) curve (AUC) of kurtosis, inhomogeneity and entropy diagnosed with malignant mass were 0.832, 0.859 and 0.891, respectively (P<0.01). In addition, the entropy was the best among the three indicators. When the entropy was ≤4.22, the sensitivity of the diagnosis Luminal B was 90.62% and the specificity was 78.95%.

CONCLUSIONS: The texture analysis features based on DCE-MRI can help to identify ER-positive breast cancer subtypes. Entropy can be the best single texture indicator.}, } @article {pmid32775010, year = {2020}, author = {Zhang, JQ and Lu, CY and Qin, L and Chen, HM and Wu, SY}, title = {Outcome of post-mastectomy radiotherapy after primary systemic treatment in patients with different clinical tumor and nodal stages of breast cancer: a cohort study.}, journal = {American journal of cancer research}, volume = {10}, number = {7}, pages = {2185-2198}, pmid = {32775010}, issn = {2156-6976}, abstract = {To evaluate the effect of post-mastectomy radiation therapy (PMRT) stratified by clinical tumor (T) or nodal (N) staging and determine predictors of overall survival (OS), locoregional recurrence (LRR), distant metastasis, and disease-free survival (DFS) in patients with breast cancer who received neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we enrolled patients who received a diagnosis of breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was employed to calculate hazard ratios (HRs) and confidence intervals (CIs). Univariate and multivariate Cox regression analyses indicated that non-PMRT, Charlson comorbidity index ≥ 2, advanced clinical T or N stage, pathologic partial response, pathologic stationary disease, or pathologic progression disease were poor prognostic factors for OS. Well-differentiated tumor grade, pathologic complete response, and positive hormone receptors were better independent prognostic factors for OS. Adjusted HRs derived from PMRT for breast cancer after NACT and TM were 0.69 (0.53-0.89) and 0.74 (0.59-0.93) in clinical T3 and T4, respectively. aHRs derived from PMRT for breast cancer after NACT and TM were 0.67 (0.45-0.99), 0.75 (0.62-0.92), and 0.77 (0.60-0.98) in clinical N0, N1, N2-3, respectively. The aHRs (95% CI) of the PMRT group to the non-PMRT group for LRR-free survival and DFS were improved significantly. Our study indicated that PMRT significantly improved OS in clinical T3N0-T4N3 and for LRR-free survival and DFS in clinical T2N0-T4N3 from those of non-PMRT patients regardless of pathologic response and other predictors.}, } @article {pmid32772474, year = {2020}, author = {Geha, RC and Taback, B and Cadena, L and Borden, B and Feldman, S}, title = {A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers.}, journal = {The breast journal}, volume = {26}, number = {11}, pages = {2157-2162}, doi = {10.1111/tbj.14004}, pmid = {32772474}, issn = {1524-4741}, support = {//Dune Medical Devices/ ; }, mesh = {*Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Intraductal, Noninfiltrating/surgery ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; Middle Aged ; Prospective Studies ; Reoperation ; Retrospective Studies ; }, abstract = {Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64 years old. The average size of the specimen was 5.6 cm, the average volume was 37.8 cm[3] , and the average weight was 32.7 g. The mean size of DCIS was 1.4 cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P < .05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.}, } @article {pmid32772437, year = {2020}, author = {Silveira, WA and Gonçalves, DA and Machado, J and Lautherbach, N and Lustrino, D and Paula-Gomes, S and Pereira, MG and Miyabara, EH and Sandri, M and Kettelhut, IC and Navegantes, LC}, title = {cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {9}, pages = {12946-12962}, doi = {10.1096/fj.201902102RR}, pmid = {32772437}, issn = {1530-6860}, mesh = {Animals ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Forkhead Box Protein O1/*metabolism ; Forkhead Box Protein O3/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*enzymology/pathology ; Muscular Atrophy/*metabolism ; Myoblasts, Skeletal/enzymology ; Signal Transduction ; }, abstract = {Although we have shown that catecholamines suppress the activity of the Ubiquitin-Proteasome System (UPS) and atrophy-related genes expression through a cAMP-dependent manner in skeletal muscle from rodents, the underlying mechanisms remain unclear. Here, we report that a single injection of norepinephrine (NE; 1 mg kg[-1] ; s.c) attenuated the fasting-induced up-regulation of FoxO-target genes in tibialis anterior (TA) muscles by the stimulation of PKA/CREB and Akt/FoxO1 signaling pathways. In addition, muscle-specific activation of PKA by the overexpression of PKA catalytic subunit (PKAcat) suppressed FoxO reporter activity induced by (1) a wild-type; (2) a non-phosphorylatable; (3) a non-phosphorylatable and non-acetylatable forms of FoxO1 and FoxO3; (4) downregulation of FoxO protein content, and probably by (5) PGC-1α up-regulation. Consistently, the overexpression of the PKAcat inhibitor (PKI) up-regulated FoxO activity and the content of Atrogin-1 and MuRF1, as well as induced muscle fiber atrophy, the latter effect being prevented by the overexpression of a dominant negative (d. n.) form of FoxO (d.n.FoxO). The sustained overexpression of PKAcat induced fiber-type transition toward a smaller, slower, and more oxidative phenotype and improved muscle resistance to fatigue. Taken together, our data provide the first evidence that endogenous PKA activity is required to restrain the basal activity of FoxO and physiologically important to maintain skeletal muscle mass.}, } @article {pmid32770432, year = {2020}, author = {Kimura, M and Narui, K and Shima, H and Ikejima, S and Muto, M and Satake, T and Tanabe, M and Inayama, Y and Adachi, S and Yamada, A and Shimada, K and Sugae, S and Ichikawa, Y and Ishikawa, T and Endo, I}, title = {Development of an invasive ductal carcinoma in a contralateral composite nipple graft after an autologous breast reconstruction: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {203}, pmid = {32770432}, issn = {2198-7793}, abstract = {BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time.

CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2.

CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.}, } @article {pmid32767139, year = {2020}, author = {Tsutsumi, C and Abe, T and Sawatsubashi, Y and Tamiya, S and Kakihara, D and Nishihara, K and Nakano, T}, title = {Synchronous solid pseudopapillary neoplasm and invasive ductal carcinoma of the pancreas: a case report.}, journal = {Surgical case reports}, volume = {6}, number = {1}, pages = {202}, pmid = {32767139}, issn = {2198-7793}, abstract = {BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare neoplasm with a favorable prognosis. On the other hand, pancreatic invasive ductal carcinoma (IDC) is known to be an aggressive malignancy. To the best of our knowledge, there is no report of SPN combined with IDC of the pancreas.

CASE PRESENTATION: A 66-year-old woman presented with abnormal genital bleeding and was diagnosed with inoperable cervical cancer. During computed tomography for cancer staging, the patient was incidentally diagnosed with pancreatic cancer. After radiation therapy for the cervical cancer, distal pancreatectomy with D2 lymph node dissection was performed. A postoperative pathological examination revealed SPN with ossification and well-differentiated IDC in the pancreatic body. On immunohistochemical staining, SPN tumor cells showed positive β-catenin and CD10 staining, whereas IDC cells were negative for both. The tumor boundaries were clear. Accordingly, the final pathological diagnosis was synchronous SPN and IDC of the pancreas. Moreover, pathological findings such as the ossification and small number of SPN cells suggested that SPN may have existed long before IDC initiation.

CONCLUSIONS: Here, we report the first case of SPN combined with IDC of the pancreas. They may occur independently, and the long-term presence of SPN may lead to the development of IDC.}, } @article {pmid32766014, year = {2020}, author = {Nguyen, QD and Tavana, A and Saenz Rios, F and Posleman Monetto, FE and Robinson, AS}, title = {A Case of Male Breast Cancer Patient with CHEK2*1100delC Mutation.}, journal = {Cureus}, volume = {12}, number = {7}, pages = {e8972}, pmid = {32766014}, issn = {2168-8184}, abstract = {Male breast cancer (MBC) is a rare disease that accounts for less than one percent of all breast cancers. The association between BRCA1 and BRCA2 mutations and MBC has been well-established; recent data suggest that CHEK2 1100delC heterozygosity is also associated with an increased risk of MBC. Herein, we present the case of a 47-year-old male who was initially diagnosed with bilateral symmetric gynecomastia on a diagnostic mammogram performed for right breast palpable lump. Sixteen months after his diagnosis of gynecomastia, he presented with enlarging right breast palpable lumps and underwent a diagnostic mammogram and breast ultrasound. Ultrasound-guided biopsies were performed on the right breast mass and axillary lymphadenopathy. Pathology revealed right breast invasive ductal carcinoma (IDC) and right axillary metastatic lymphadenopathy. Subsequent genetic testing found CHEK2*1100delC mutation. This case report focuses on the presentation, diagnosis, and management of breast cancer, as well as long-term cancer screening in the setting of CHEK2 mutation in a relatively young male patient.}, } @article {pmid32762289, year = {2022}, author = {Keisari, S and Feniger-Schaal, R and Palgi, Y and Golland, Y and Gesser-Edelsburg, A and Ben-David, B}, title = {Synchrony in Old Age: Playing the Mirror Game Improves Cognitive Performance.}, journal = {Clinical gerontologist}, volume = {45}, number = {2}, pages = {312-326}, doi = {10.1080/07317115.2020.1799131}, pmid = {32762289}, issn = {1545-2301}, mesh = {Affect ; Aged ; *Cognition ; *Emotions ; Exercise ; Humans ; }, abstract = {OBJECTIVES: Studies have shown that synchronized motion between people positively affects a range of emotional and social functions. The mirror-game is a synchrony-based paradigm, common to theater, performance arts, and therapy, which includes dyadic synchronized motion, playfulness, and spontaneity. The goal of the current study is to examine the effects of the mirror-game on subjective and cognitive indices in late life.

METHODS: Thirty-four older adults (aged 71-98) participated in a within-group study design. Participants conducted two sessions of 9-minute movement activities: the mirror-game and the control condition - a physical exercise class. Several measures were taken before and after experimental sessions to assess socio-emotional and attentional functions.

RESULTS: The mirror-game enhanced performance on the attention sub-scale and led to faster detections of spoken words in noise. Further, it enhanced perceived partner responsiveness and led to an increase in positive reported experience.

CONCLUSIONS: Our preliminary findings suggest that the mirror-game, rather than the exercise class, may have an immediate impact on mood and some attentional functions.

CLINICAL IMPLICATIONS: The mirror-game is a novel intervention, with potential benefits of social-emotional and cognitive functioning, which can be easily implemented into the daily routine care of older adults. Future studies should explore the effect of the mirror-game on additional cognitive and socio-emotional aspects.}, } @article {pmid32762104, year = {2021}, author = {Falicov, C and Nakash, O and Alegría, M}, title = {Centering the Voice of the Client: On Becoming a Collaborative Practitioner with Low-Income Individuals and Families.}, journal = {Family process}, volume = {60}, number = {2}, pages = {670-687}, pmid = {32762104}, issn = {1545-5300}, support = {CD-12-11-4187/PCORI/Patient-Centered Outcomes Research Institute/United States ; }, mesh = {Communication ; Emotions ; Humans ; *Professional-Patient Relations ; *Psychotherapy ; }, abstract = {Despite current interest in collaborative practices, few investigations document the ways practitioners can facilitate collaboration during in-session interactions. This investigation explores verbatim psychotherapy transcripts to describe and illustrate therapist's communications that facilitate or hinder centering client's voice in work with socioeconomically disadvantaged populations. Four exemplar cases were selected from a large intervention trial aimed at improving shared decision making (SDM) skills of psychotherapists working with low-income clients. The exemplar cases were selected because they showed therapist's different degrees of success in facilitating SDM. Therapist's verbalizations were grouped into five distinct communicative practices that centered or de-centered the voice of clients. Communication practices were examined through the lens of collaborative approaches in family therapy. The analysis suggests that cross-fertilization between SDM and family-oriented collaborative and critical approaches shows promise to illuminate and enhance the challenging road from clinician-led to client-led interactions. This paper also stresses the importance of incorporating relational intersectionality with individuals and families who may not feel entitled to express their expectations or raise questions when interacting with authority figures.}, } @article {pmid32758491, year = {2020}, author = {Sechrist, H and Glasgow, A and Bomeisl, P and Gilmore, H and Harbhajanka, A}, title = {Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.}, journal = {Human pathology}, volume = {104}, number = {}, pages = {54-65}, doi = {10.1016/j.humpath.2020.07.022}, pmid = {32758491}, issn = {1532-8392}, mesh = {Aged ; *Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology/therapy ; Clinical Decision-Making ; Female ; *Gene Expression Profiling ; Humans ; *Immunohistochemistry ; *In Situ Hybridization ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Receptor, ErbB-2/analysis/genetics ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Retrospective Studies ; *Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; Transcriptome ; Treatment Outcome ; }, abstract = {Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.}, } @article {pmid32756100, year = {2020}, author = {Lee, J and Yang, JD and Lee, JW and Li, J and Jung, JH and Kim, WW and Park, CS and Lee, JS and Park, HY}, title = {Acellular dermal matrix combined with oxidized regenerated cellulose for partial breast reconstruction: Two case reports.}, journal = {Medicine}, volume = {99}, number = {31}, pages = {e21217}, pmid = {32756100}, issn = {1536-5964}, mesh = {Acellular Dermis ; Breast Neoplasms/*surgery ; Carcinoma, Ductal/*surgery ; Cellulose, Oxidized/administration & dosage ; Female ; Humans ; Mammaplasty ; Mastectomy, Segmental ; Middle Aged ; Treatment Outcome ; }, abstract = {RATIONALE: Filling materials for partial defect of the breast have rarely been developed because of safety and durability.

PATIENT CONCERNS: Two female patients (ages, 53 and 50 years) with breast cancer underwent partial mastectomy with sentinel lymph node biopsy.

DIAGNOSIS: Core needle biopsy revealed an invasive ductal carcinoma in both patients. Breast ultrasound showed hypoechoic nodules with irregular margins. Breast magnetic resonance imaging showed an irregularly shaped enhancing mass with duct extension in Patient 1 and irregularly shaped multifocal, enhancing masses with non-mass enhancement in Patient 2.

INTERVENTION: A combination method using acellular dermal matrix and oxidized regenerated cellulose was used for partial breast reconstruction. The safety and cosmetic outcomes were evaluated for both patients.

OUTCOMES: There were no significant complications, and the breast shape and volume were well maintained, even 2 years after surgery. There was no postoperative tumor recurrence.

CONCLUSION: The combination of acellular dermal matrix and oxidized regenerated cellulose for partial breast reconstruction can be a good option based on oncological safety and cosmetic outcome.}, } @article {pmid32754680, year = {2020}, author = {Keshavarzi, B and Tabatabaei, M and Zarnani, AH and Tehrani, FR and Bozorgmehr, M and Mosaffa, N}, title = {The effect of human amniotic epithelial cell on dendritic cell differentiation of peripheral blood monocytes: An experimental study.}, journal = {International journal of reproductive biomedicine}, volume = {18}, number = {6}, pages = {449-464}, pmid = {32754680}, issn = {2476-4108}, abstract = {BACKGROUND: The amniotic membrane plays an important role in maintaining a healthy pregnancy. The main population cells from amniotic membrane include human amnion epithelial cells (hAECs) which have been shown to possess immunomodulatory properties.

OBJECTIVE: The proximity of hAECs with monocyte leads to the generation of tollerogenic dendritic cells.

MATERIALS AND METHODS: hAECs were obtained from normal pregnancy. Peripheral blood monocytes were isolated by anti-CD14 MACS method. Co-cultures of monocytes and hAECs were established in Transwell chambers supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in the absence and presence of lipopolysaccharide (LPS) to produce immature and mature DCs, respectively. Immunophenotyping of the obtained DCs was done through flow cytometry and the production of cytokines was measured by ELISA. Mixed leukocyte Reaction (MLR) was also performed for the functional assessment of DCs.

RESULTS: Immunophenotyping of [hAECs - Immature DC (iDC)] and [hAECs - iDC] + LPS cells revealed that the expression of CD1a, CD80, CD86, CD40, HLA-DR, and CD83 markers showed no significant difference as compared with the control group (iDCs and mDCs alone). In the [hAECs-iDCs] + LPS cells, the percentage of CD14 cells at the ratio of 1:2.5 showed significant differences compared to the control group. The production of IL-10 and IL-12 showed no significant difference in any of the cultures as compared to the control groups. Also, co-cultured DCs did not inhibit proliferation of lymphocyte.

CONCLUSION: Our findings show that factors secreted from cultured hAECs are unable to generate of tollerogenic dendritic cells. To achieve a better understanding of other mechanisms more investigations are needed.}, } @article {pmid32754217, year = {2020}, author = {Hashemi Bahremani, M and Ebrahimi, A and Fallahi, M}, title = {Predicting Effects of Clinicopathological Variables on Her2 Gene Amplification by Chromogenic in situ Hybridization (CISH) in IHC Her2 (2+) Breast Cancer Patients; A Study from Iran.}, journal = {Iranian journal of pathology}, volume = {15}, number = {3}, pages = {217-224}, pmid = {32754217}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: The her2 amplification plays an important role in breast cancer management. Therefore, there is a need for using supplementary molecular methods in IHC equivocal cases. Present study has been conducted to determine the effects of clinicopathological variables on her2 gene amplification by chromogenic in situ hybridization (CISH) in IHC Her2 (2+) breast cancer individuals.

METHODS: A cross-sectional study was conducted in Zaferanyeh Laboratory collaborated with Shahid Beheshti University of Medical Sciences (Tehran-Iran; 2015-2018). All pathological data related invasive breast cancer patients with equivocal IHC results were included. CISH method was performed as a supplementary technique. The associations between histopathologic variables, status of Ki-67 index, progesterone and estrogen receptors (PR & ER) with her2 amplification by CISH were investigated and analyzed. The level of significance was considered as P-value < 0.05.

RESULTS: Totally, 239 patients with mean age of 53.2 years were studied. CISH identified her2 gene amplification in 51 subjects (21.3%). The type of tumor (invasive ductal carcinoma), the tumor grade, and the value of Ki-67 index were directly correlated with her2 amplification. Significant negative associations were also observed between CISH results and ER and PR expression.

CONCLUSION: As her2 gene amplification was identified in 21.3% of invasive breast cancer patients with equivocal IHC results, it is supposed that applying CISH method may consider as a potentially valuable supplementary method. Results have also shown that higher grades of tumor, invasive ductal carcinoma, absences of hormone receptors and high Ki-67 index significantly correlated with the her2 amplification.}, } @article {pmid32753069, year = {2020}, author = {Choridah, L and Sari, WK and Dwianingsih, EK and Widodo, I and Suwardjo, and Anwar, SL}, title = {Advanced lesions of synchronous bilateral mammary Paget's disease: a case report.}, journal = {Journal of medical case reports}, volume = {14}, number = {1}, pages = {119}, pmid = {32753069}, issn = {1752-1947}, support = {PPUPT 2274/2019//Kementerian Riset, Teknologi dan Pendidikan Tinggi/ ; Dana Masyarakat 1499/2019//Universitas Gadjah Mada/ ; RTA Nr 133/2607-2020//Universitas Gadjah Mada/ ; 1/2018//NUS-UGM-Tahir Foundation/ ; }, mesh = {*Breast Neoplasms/diagnosis/surgery ; Female ; Humans ; Indonesia ; Mastectomy ; Middle Aged ; Nipples ; *Paget's Disease, Mammary/diagnostic imaging/surgery ; }, abstract = {BACKGROUND: Mammary Paget's disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget's disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient's physical, psychological, and social aspects of well-being.

CASE PRESENTATION: A 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget's cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%).

CONCLUSIONS: In a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.}, } @article {pmid32749847, year = {2020}, author = {Gatek, J and Petru, V and Kosac, P and Ratajsky, M and Duben, J and Dudesek, B and Jancik, P and Zabojnikova, M and Katrusak, J and Opelova, P and Podrazska, L and Vazan, P and Kudlova, P and Holik, P and Melichar, B and Vrana, D}, title = {Targeted axillary dissection with preoperative tattooing of biopsied positive axillary lymph nodes in breast cancer.}, journal = {Neoplasma}, volume = {67}, number = {6}, pages = {1329-1334}, doi = {10.4149/neo_2020_191228N1344}, pmid = {32749847}, issn = {0028-2685}, mesh = {Axilla/pathology ; *Breast Neoplasms/drug therapy/pathology/surgery ; Dissection ; Female ; Humans ; *Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Staging ; Prospective Studies ; Sentinel Lymph Node Biopsy ; *Tattooing ; }, abstract = {Sentinel lymph node biopsy (SLNB) has emerged as an alternative to axillary lymph node dissection during breast cancer surgery during the last 2 decades. However, there are several controversies regarding the indication of the sentinel node biopsy after neoadjuvant chemotherapy which can convert positive lymph nodes to negative. The false-negative rate after neoadjuvant chemotherapy is unacceptably high. This high false-negative rate can be decreased by marking of the positive lymph nodes and removal during sentinel lymph node biopsy procedure in addition to the sentinel lymph nodes. The aim of this study was to investigate the possibility of carbon tattooing of the positive sentinel lymph nodes before neoadjuvant chemotherapy. In 2016, a prospective protocol was launched investigating the black carbon tattooing procedure of the suspective and positive axillary lymph nodes by injecting 0.1-0.5 carbon ink in normal saline under ultrasound guidance. All patients underwent black carbon tattooing of the suspected or positive axillary lymph nodes before the chemotherapy or one week before the primary surgery when chemotherapy was not indicated in the neoadjuvant setting. Sentinel lymph nodes together with lymph nodes marked by the black carbon ink were removed and histologically evaluated. So far 27 patients were treated under this protocol. Breast saving surgery was performed in 22 cases and mastectomy in 5 cases. All patients had invasive ductal carcinoma. In 20 patients neoadjuvant chemotherapy was indicated and in 7 patients primary surgery was performed. All lymph nodes marked by black carbon ink were successfully identified and removed. Sentinel lymph node biopsy was performed in 8 cases and sentinel lymph node biopsy followed by axillary dissection in 15 cases. Axillary dissection alone was performed in 4 cases. In 19 cases, the black carbon ink was present in the sentinel lymph node at the same time and in 4 cases carbon dye was present in other lymph nodes than the lymph node identified during SLNB, which corresponds to 17.4%. In the group of patients undergoing primary surgery, in one case from six, the sentinel lymph node was negative and the lymph node marked with carbon ink positive which represents false-negative lymph node and failure of the SLNB procedure. After neoadjuvant chemotherapy, there was no false-negative lymph node identified, but the conversion of the positive lymph nodes to negative was present in 10 cases (50%). There were no complications attributed to carbon ink tattooing. The results of positive sentinel lymph nodes tattooing have confirmed that this method is safe and allows a decrease in the false negativity rate during the sentinel node biopsy procedure.}, } @article {pmid32748295, year = {2020}, author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Naito, Y and Tochigi, K and Sano, T and Ishida, S and Funahashi, Y and Fujita, T and Matsukawa, Y and Hattori, R and Tsuzuki, T}, title = {Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.}, journal = {International journal of clinical oncology}, volume = {25}, number = {12}, pages = {2130-2137}, pmid = {32748295}, issn = {1437-7772}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Bone Neoplasms/secondary ; Carcinoma, Ductal/mortality/*pathology ; Hormones ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/mortality/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).

METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.

RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively).

CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.}, } @article {pmid32745951, year = {2020}, author = {Altinoz, A and Al Ameri, M and Qureshi, W and Boush, N and Nair, SC and Abdel-Aziz, A}, title = {Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.}, journal = {Breast (Edinburgh, Scotland)}, volume = {53}, number = {}, pages = {119-124}, pmid = {32745951}, issn = {1532-3080}, mesh = {Adult ; Arabs/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease/*epidemiology/ethnology/genetics ; Genetic Testing/statistics & numerical data ; Hereditary Breast and Ovarian Cancer Syndrome/ethnology/*genetics/pathology ; Humans ; Middle Aged ; Prevalence ; Retrospective Studies ; United Arab Emirates/epidemiology ; }, abstract = {INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE.

MATERIAL & METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation.

RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (±9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%).

CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.}, } @article {pmid32740809, year = {2020}, author = {Gao, W and Zeng, Y and Fei, X and Chen, X and Shen, K}, title = {Axillary lymph node and non-sentinel lymph node metastasis among the ACOSOG Z0011 eligible breast cancer patients with invasive ductal, invasive lobular, or other histological special types: a multi-institutional retrospective analysis.}, journal = {Breast cancer research and treatment}, volume = {184}, number = {1}, pages = {193-202}, doi = {10.1007/s10549-020-05842-9}, pmid = {32740809}, issn = {1573-7217}, support = {81772797//National Natural Science Foundation of China/ ; 20172007//Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support/ ; GCQN-2017-A18//Ruijin Hospital, Shanghai Jiao Tong University School of Medicine-Guangci Excellent Youth Training Program/ ; }, mesh = {Axilla ; *Breast Neoplasms/surgery ; *Carcinoma, Ductal, Breast/surgery ; *Carcinoma, Lobular/drug therapy/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; }, abstract = {PURPOSE: Given the histological special types (HST) of breast carcinoma accounted for minority of the Z0011 study population, this study aimed to assess the rates of axillary lymph node (ALN) involvement and non-sentinel lymph node (SLN) metastasis in patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or other HST.

METHODS: Patients with cT1-2N0M0 breast cancer treated between 2009 and 2018 were retrospectively included from a multi-institutional database. Rates of nodal involvement were analyzed among different histological subgroups. The impact of ALN dissection (ALND) on adjuvant treatment decisions and prognosis were also analyzed among patients with 1-2 + SLNs.

RESULTS: A total of 8294 patients were included: 6854 (82.6%), 257 (3.1%), and 1183 (14.3%) patients with IDC, ILC, and other HST, respectively. IDC patients had a significantly higher rate of ALN metastasis compared with ILC or other HST (31.9% vs. 22.6% vs. 16.4%, P < 0.001). However, in patients with 1-2 + SLNs, rates of non-SLN metastasis were similar among three groups (IDC: n = 182, 28.6% vs. ILC: n = 5, 31.2% vs. other HST: n = 29, 34.9%, P = 0.481). For patients with 1-2 + SLNs, rates of adjuvant chemotherapy and the estimated 3-year recurrence-free survival were similar between the SLN biopsy and ALND arms, regardless of the histological types.

CONCLUSION: Among patients with 1-2 + SLNs, ILC or other HST had similar rates of non-SLN metastasis compared with IDC. Omission of ALND may not influence adjuvant chemotherapy usage or disease outcome regardless of histological types.}, } @article {pmid32740271, year = {2020}, author = {Granek, L and Nakash, O}, title = {Prevalence and risk factors for suicidality in cancer patients and oncology healthcare professionals strategies in identifying suicide risk in cancer patients.}, journal = {Current opinion in supportive and palliative care}, volume = {14}, number = {3}, pages = {239-246}, pmid = {32740271}, issn = {1751-4266}, mesh = {Age Factors ; Cancer Care Facilities/organization & administration ; Health Personnel/education/*organization & administration ; Humans ; Inservice Training ; Mass Screening/organization & administration ; Neoplasms/pathology/*psychology ; Prevalence ; Risk Factors ; Sex Factors ; Socioeconomic Factors ; Suicide/*statistics & numerical data ; }, abstract = {PURPOSE OF REVIEW: The aim of this study was to summarize the literature on prevalence and risk factors for suicidality in cancer patients and to document the research on oncology healthcare professionals' strategies in identifying this risk.

RECENT FINDINGS: Cancer patients exhibit increased risk of suicidality compared with the general population. Various risk factors have been identified including sociodemographic factors such as poverty, being male and elderly as well as disease-related attributes such as cancer type and stage. The literature on how healthcare professionals identify suicide risk is sparse. Ten articles were found that focused on two main themes. These included information on systematic strategies in identifying suicide risk and factors that affect healthcare professionals' ability to identify risk in their patients.

SUMMARY: Although there is an immense amount of literature documenting the problem of suicidality among patients, the research on how healthcare professionals identify and respond to these indications in patients is nearly nonexistent. Cancer centres should implement standardized and systematic screening of cancer patients for suicidality and research on this patient population should collect and report these data. Ongoing training and education for healthcare professionals who work in the oncology setting on how to identify and respond to suicide risk among cancer patients is urgently needed.}, } @article {pmid32738662, year = {2020}, author = {Cerea, S and Ghisi, M and Bottesi, G and Carraro, E and Broggio, D and Doron, G}, title = {Reaching reliable change using short, daily, cognitive training exercises delivered on a mobile application: The case of Relationship Obsessive Compulsive Disorder (ROCD) symptoms and cognitions in a subclinical cohort.}, journal = {Journal of affective disorders}, volume = {276}, number = {}, pages = {775-787}, doi = {10.1016/j.jad.2020.07.043}, pmid = {32738662}, issn = {1573-2517}, mesh = {Cognition ; Exercise ; Humans ; *Mobile Applications ; *Obsessive-Compulsive Disorder/therapy ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Relationship Obsessive Compulsive Disorder (ROCD) is a presentation of OCD centering on interpersonal relationships. The aim of this Randomized Control Trial (RCT) was to assess the efficacy of short, game like, daily cognitive interventions delivered via mobile application in reducing subclinical ROCD symptoms and associated phenomena.

METHODS: Fifty university students identified as having subclinical levels of ROCD symptoms (using the Structured Clinical Interview for DSM-5 Clinical Version) were randomized into: immediate-use group (iApp group; n = 25) and delayed-use group (dApp group; n = 25). The iApp group started using the evaluated cognitive-behavioral training application at baseline for 15 days (T0 to T1). The dApp group commenced using the application at T1 for 15 days (T1 to T2). All participants completed questionnaires at baseline (T0), 15 days from baseline (T1), and 30 days from baseline (T2).

RESULTS: Repeated measure MANOVAs showed significant Group (iApp vs. dApp) × Time (T0 vs. T1) interactions. These interactions indicated greater decrease in ROCD symptoms, OCD beliefs and social anxiety symptoms, as well as a greater increase in self-esteem in the iApp group compared to dApp group at T1. Moreover, the Reliable Change Index (RCI) indicated reliable change on ROCD symptoms for a significant portion of participants (42-52%).

LIMITATIONS: Sample size and the use of self-report measures limits the generalizability of the results.

CONCLUSIONS: Short, daily cognitive training interventions delivered via mobile applications may be useful in reducing subclinical ROCD symptoms and associated features. Further testing is needed for clinical populations.}, } @article {pmid32738557, year = {2020}, author = {Lilly, AJ and Johnson, M and Kuzmiak, CM and Ollila, DW and O'Connor, SM and Hertel, JD and Calhoun, BC}, title = {MRI-guided core needle biopsy of the breast: Radiology-pathology correlation and impact on clinical management.}, journal = {Annals of diagnostic pathology}, volume = {48}, number = {}, pages = {151563}, pmid = {32738557}, issn = {1532-8198}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biopsy, Large-Core Needle/*instrumentation ; Breast/*diagnostic imaging/*pathology ; Breast Neoplasms/pathology/surgery ; Female ; Humans ; Image-Guided Biopsy/methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasms/diagnostic imaging/pathology/surgery ; Patient Care Management/methods/trends ; Radiology ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {OBJECTIVE: Breast MRI is used to screen high-risk patients and determine extent of disease in breast cancer (BC) patients. The goal of this study was to determine the pathologic correlates of breast MRI abnormalities biopsied under MRI guidance.

METHODS: We retrospectively identified 101 MRI-guided core needle biopsies (CNB) of the breast from 79 women over a 4-year period. MRI-detected lesions biopsied with ultrasound or stereotactic guidance were excluded. MRI studies and pathology were reviewed by breast radiologists and pathologists.

RESULTS: Of the 79 patients, 72 (91%) had a history of prior (n = 13) or concurrent (n = 59) BC. There were 101 MRI abnormalities: 60 (59%) with non-mass enhancement (NME) and 41 (41%) with mass enhancement. Pathology was benign in 83/101 (82%), including in the majority of NME lesions (43/60, 72%). The most common benign findings were: fibrocystic changes (FCC) (49%), sclerosing lesions (13%), and fibroadenoma (FA) (9%). There were 18 (18%) malignant diagnoses: 8 (44%) invasive lobular carcinoma (ILC), 7 (39%) ductal carcinoma in situ (DCIS), and 3 (17%) invasive ductal carcinoma (IDC). Of the 18 malignant diagnoses, 16 (89%) occurred in 14 unique patients with concurrent BC. Based on the malignant MRI-guided CNB, 6 (46%) of these patients had additional (sentinel lymph node biopsy or contralateral breast surgery) or more extensive (wider lumpectomy) surgery.

CONCLUSION: In this series, most MRI-guided CNB of the breast were benign. The vast majority of malignant diagnoses occurred in patients with concurrent BC and frequently resulted in changes in clinical management.}, } @article {pmid32738354, year = {2021}, author = {Camacho Londoño, JE and Kuryshev, V and Zorn, M and Saar, K and Tian, Q and Hübner, N and Nawroth, P and Dietrich, A and Birnbaumer, L and Lipp, P and Dieterich, C and Freichel, M}, title = {Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca[2+] entry after pressure-overload induced cardiac remodelling.}, journal = {Progress in biophysics and molecular biology}, volume = {159}, number = {}, pages = {86-104}, doi = {10.1016/j.pbiomolbio.2020.07.006}, pmid = {32738354}, issn = {1873-1732}, support = {Z01 ES101684/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena/physiology ; Calcium/*metabolism ; Calcium Signaling ; Cardiomegaly/metabolism ; Gene Expression Regulation ; Humans ; Ion Channels/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Myocytes, Cardiac/*metabolism ; TRPC Cation Channels/*metabolism ; Transcriptional Activation/physiology ; Ventricular Remodeling/*physiology ; }, abstract = {AIMS: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca[2+] entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.

METHODS AND RESULTS: Mn[2+]-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (-51.4%) or after one week of transverse aortic constriction (TAC; -73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts.

CONCLUSIONS: Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.}, } @article {pmid32733648, year = {2020}, author = {Laurito, S and Branham, MT and Campoy, E and Real, S and Cueto, J and Urrutia, G and Gago, F and Tello, O and Glatstein, T and De la Iglesia, P and Atanesyan, L and Savola, S and Roqué, M}, title = {Working together for the family: determination of HER oncogene co-amplifications in breast cancer.}, journal = {Oncotarget}, volume = {11}, number = {28}, pages = {2774-2792}, pmid = {32733648}, issn = {1949-2553}, abstract = {HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r [2] = 0,91, p < 0,0001), CISH (Adjusted r [2] = 0,938, p < 0,0001) and IHC (Adjusted r [2] = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.}, } @article {pmid32733646, year = {2020}, author = {Murali, P and Johnson, BP and Lu, Z and Climer, L and Scott, DA and Foulquier, F and Oprea-Ilies, G and Lupashin, V and Drake, RR and Abbott, KL}, title = {Novel role for the Golgi membrane protein TMEM165 in control of migration and invasion for breast carcinoma.}, journal = {Oncotarget}, volume = {11}, number = {28}, pages = {2747-2762}, pmid = {32733646}, issn = {1949-2553}, support = {R01 GM083144/GM/NIGMS NIH HHS/United States ; U01 CA226055/CA/NCI NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; P30 CA225520/CA/NCI NIH HHS/United States ; U01 CA168870/CA/NCI NIH HHS/United States ; }, abstract = {The TMEM165 gene encodes for a multiple pass membrane protein localized in the Golgi that has been linked to congenital disorders of glycosylation. The TMEM165 protein is a putative ion transporter that regulates H[+]/Ca[++]/Mn[++] homeostasis and pH in the Golgi. Previously, we identified TMEM165 as a potential biomarker for breast carcinoma in a glycoproteomic study using late stage invasive ductal carcinoma tissues with patient- matched adjacent normal tissues. The TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry. Our hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer. In this preliminary study we have investigated the expression of TMEM165 in earlier stage invasive ductal carcinoma and ductal carcinoma in situ cases. We created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231. Our results indicate that removal of TMEM165 in these cells results in a significant reduction of cell migration, tumor growth, and tumor vascularization in vivo. Furthermore, we find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in regulation of the epithelial to mesenchymal transition such as E-cadherin. These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion.}, } @article {pmid32729645, year = {2020}, author = {Botty Van den Bruele, A and Gemignani, ML}, title = {Management of ipsilateral supernumerary nipple at time of breast cancer diagnosis.}, journal = {The breast journal}, volume = {26}, number = {10}, pages = {2042-2044}, pmid = {32729645}, issn = {1524-4741}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Diseases ; *Breast Neoplasms/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery ; *Carcinoma, Intraductal, Noninfiltrating/surgery ; Female ; Humans ; Mastectomy ; Nipples/surgery ; }, abstract = {Supernumerary breast components occur predominantly between the breast and umbilicus. Carcinoma of this ectopic, or accessory breast tissue (ABT), is exceedingly rare, accounting for <1% of breast cancer cases. Historically, ectopic breast carcinoma was considered aggressive with poor outcome. In 1995, Evans et al reported 90 cases spanning from 1929 to 1993 with a 9.4% survival beyond 4 years. More contemporary studies reveal improvement in both treatment and survival. There is currently no consensus on whether prophylactic excision of an ipsilateral supernumerary nipple at the time of initial breast cancer diagnosis is necessary. The following describes a patient with an ipsilateral tumor uniquely located within her supernumerary nipple 5 years after mastectomy.}, } @article {pmid32727156, year = {2020}, author = {Mutlu, EC and Kaya, Ö and Wood, M and Mager, I and Topkara, KÇ and Çamsarı, Ç and Birinci Yildirim, A and Çetinkaya, A and Acarel, D and Odabaşı Bağcı, J}, title = {Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial.}, journal = {Materials (Basel, Switzerland)}, volume = {13}, number = {15}, pages = {}, pmid = {32727156}, issn = {1996-1944}, abstract = {Immature dendritic cells (IDc), 'dexosomes', are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/10[6] cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMask[TM] membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between -15 to -20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the "BioNanoMaterial" after DOX loading via ultrasonication technique.}, } @article {pmid32725525, year = {2020}, author = {Findlay-Shirras, LJ and Lima, I and Smith, G and Clemons, M and Arnaout, A}, title = {Population Trends in Lobular Carcinoma of the Breast: The Ontario Experience.}, journal = {Annals of surgical oncology}, volume = {27}, number = {12}, pages = {4711-4719}, doi = {10.1245/s10434-020-08895-8}, pmid = {32725525}, issn = {1534-4681}, mesh = {Adolescent ; *Breast Neoplasms/epidemiology ; *Carcinoma, Lobular/epidemiology ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Ontario/epidemiology ; Retrospective Studies ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is less common that invasive ductal carcinoma (IDC), and more challenging to diagnose by examination and screening mammography. This study evaluated current trends in ILC incidence, and described the 5-, 10-, and 15-year survival probabilities for women diagnosed with ILC in Ontario, Canada.

METHODS: This retrospective cohort analysis included all women aged 18 years and older diagnosed with breast cancer between 1991 and 2015. Health administrative data from the Institute of Clinical Evaluative Sciences and the Ontario Cancer Registry were used to identify breast cancer cases. Age-adjusted incidence was plotted by year. Crude proportions were plotted by year of diagnosis for stage and hormone receptor status. Kaplan-Meier curves were generated to determine the 5-, 10-, and 15-year survival probabilities for ILC and IDC.

RESULTS: From 1991 to 2015, there were 194,065 cases of breast cancer in Ontario, 14.7% of which were ILC. The age-adjusted incidence of breast cancer increased 1.04-fold, while ILC rates increased 1.53-fold. All bilateral breast cancers were of lobular origin. The proportion of stage 1 ILC decreased, while the proportion of stage 2-4 ILC increased. The 5-, 10-, and 15-year overall survival probabilities for women diagnosed with ILC were 82.7%, 65.3%, and 50.2%, respectively.

CONCLUSIONS: This study contains the largest population dataset of ILC evaluated to date. While total breast cancer incidence rates in Ontario are largely unchanged, ILC incidence rates are steadily increasing and there is a trend towards diagnosis of ILC at a later stage. These trends highlight the ongoing diagnostic and treatment challenge ILC presents for patients and clinicians.}, } @article {pmid32723248, year = {2020}, author = {Yilmaz, TF and Sari, L and Temur, HO and Toprak, H and Yildiz, Ş}, title = {A Case Series of Malign Hyperechoic Breast Lesions.}, journal = {Current medical imaging}, volume = {16}, number = {6}, pages = {766-773}, doi = {10.2174/1573405615666190828162202}, pmid = {32723248}, issn = {1573-4056}, mesh = {Adult ; Aged ; Breast Carcinoma In Situ/diagnostic imaging ; Breast Diseases/*diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Calcinosis/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Elasticity Imaging Techniques ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/diagnostic imaging ; Mammography/*methods ; Middle Aged ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Hyperechoic breast lesions are a rare group of breast masses in routine practice. Most of these lesions are benign. However, they rarely may be malignant. Hyperechoic lesions can be evaluated using the same criteria for malignant lesions. Clinical history, mammographic appearance, and certain sonographic features (non-circumscribed margins, irregular shape, presence of hypoechoic areas, nonparallel orientation, and association with microcalcifications can be suggestive of malignancy). In this article, hyperechoic breast lesions with malignant pathology have been presented.

METHODS: Seven cases during breast ultrasound examination were detected.

RESULTS: Four patients had invasive ductal carcinoma, 1 patient had invasive lobular carcinoma, 1 patient had high-grade ductal carcinoma in situ (DCIS), and 1 patient had lymphoma. Ultrasonography of the breast showed a heterogeneous appearance in all the patients, microcalcification in two patients, and an ambiguous contour in one patient.

CONCLUSION: Hyperechoic breast lesions should be evaluated using specific sonographic criteria to prevent misdiagnosis and identify patients who require biopsy and further examination.}, } @article {pmid32719289, year = {2020}, author = {Dhia, SB and Belaid, I and Stita, W and Hochlaf, M and Ezzairi, F and Ahmed, SB}, title = {Bilateral parotid gland metastasis from a breast invasive ductal carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {16}, number = {3}, pages = {672-674}, doi = {10.4103/jcrt.JCRT_1047_17}, pmid = {32719289}, issn = {1998-4138}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/therapy ; Palliative Care ; Parotid Neoplasms/*secondary/therapy ; }, abstract = {Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.}, } @article {pmid32714691, year = {2020}, author = {Nguyen, QD and Nguyen, NT and Dixon, L and Posleman Monetto, FE and Robinson, AS}, title = {Spontaneously Disappearing Calcifications in the Breast: A Rare Instance Where a Decrease in Size on Mammogram Is Not Good.}, journal = {Cureus}, volume = {12}, number = {6}, pages = {e8753}, pmid = {32714691}, issn = {2168-8184}, abstract = {Spontaneously resolving breast calcification on mammography is a rare radiologic finding. This phenomenon is defined by a decrease in number and/or prominence of breast calcifications on mammogram when compared to prior imaging. The significance of resolving breast calcifications remains unclear, but they have been reported in cases of malignancy. In current literature, patients whose imaging illustrated a decrease in calcifications usually had other concomitant breast complaints. We are presenting a case of invasive ductal carcinoma, in which the patient was asymptomatic on physical examination. Spontaneously resolving breast calcification and lymphadenopathy were the only abnormal findings on screening mammogram.}, } @article {pmid32710711, year = {2020}, author = {Jones, B and Thomas, G and Sprenger, J and Nofech-Mozes, S and Khorasani, M and Vitkin, A}, title = {Peri-tumoural stroma collagen organization of invasive ductal carcinoma assessed by polarized light microscopy differs between OncotypeDX risk group.}, journal = {Journal of biophotonics}, volume = {13}, number = {11}, pages = {e202000188}, doi = {10.1002/jbio.202000188}, pmid = {32710711}, issn = {1864-0648}, support = {PJT-156110//CIHR/Canada ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/genetics ; Collagen ; Female ; Humans ; Microscopy, Polarization ; Risk Factors ; }, abstract = {A commercially available genomic test, OncotypeDX has emerged as a useful postsurgical treatment guide for early stage breast cancer. Despite widespread clinical adoption, there remain logistical issues with its implementation. Collagenous stromal architecture has been shown to hold prognostic value that may complement OncotypeDX. Polarimetric analysis of breast cancer surgical samples allows for the quantification of collagenous stroma abundance and organization. We examine intratumoural collagen abundance and alignment along the tumor-host interface for 45 human samples of invasive ductal carcinoma categorized as low or higher risk by OncotypeDX. Furthermore, we probe the separatory power of collagen alignment patterns to classify unlabeled samples as low or higher OncotypeDX risk group using a linear discriminant (LD) model. No significant difference in mean collagen abundance was found between the two risk groups. However, collagen alignment along the tumor boundary was found to be significantly lower in higher risk samples. The LD model achieved a 71% total accuracy and 81% sensitivity to higher risk samples. Prognostic information extracted from the stromal morphology has potential to complement OncotypeDX as an easy-to-implement prescreening methodology.}, } @article {pmid32709582, year = {2021}, author = {Zhou, J and Tan, H and Li, W and Liu, Z and Wu, Y and Bai, Y and Fu, F and Jia, X and Feng, A and Liu, H and Wang, M}, title = {Radiomics Signatures Based on Multiparametric MRI for the Preoperative Prediction of the HER2 Status of Patients with Breast Cancer.}, journal = {Academic radiology}, volume = {28}, number = {10}, pages = {1352-1360}, doi = {10.1016/j.acra.2020.05.040}, pmid = {32709582}, issn = {1878-4046}, mesh = {*Breast Neoplasms/diagnostic imaging ; Female ; Humans ; *Multiparametric Magnetic Resonance Imaging ; Receptor, ErbB-2 ; Retrospective Studies ; }, abstract = {OBJECTIVES: The aim of our study was to preoperatively predict the human epidermal growth factor receptor 2 (HER2) status of patients with breast cancer using radiomics signatures based on single-parametric and multiparametric magnetic resonance imaging (MRI).

METHODS: Three hundred six patients with invasive ductal carcinoma of no special type (IDC-NST) were retrospectively enrolled. Quantitative imaging features were extracted from fat-suppressed T2-weighted and dynamic contrast-enhanced T1 weighted (DCE-T1) preoperative MRI. Then, three radiomics signatures based on fat-suppressed T2-weighted images, DCE-T1 images and their combination were developed using a support vector machine (SVM) to predict the HER2-positive vs HER2-negative status of patients with breast cancer. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the predictive performances of the signatures.

RESULTS: Twenty-eight quantitative radiomics features, namely, 14 texture features, 4 first-order features, 9 wavelet features, and 1 shape feature, were used to construct radiomics signatures. The performance of the radiomics signatures for distinguishing HER2-positive from HER2-negative breast cancer based on fat-suppressed T2-weighted images, DCE-T1 images, and their combination had an AUC of 0.74 (95% confidence interval [CI], 0.700 to 0.770), 0.71 (0.673 to 0.738), and 0.86 (0.832 to 0.882) in the primary cohort and 0.70 (0.666 to 0.744), 0.68 (0.650 to 0.726), and 0.81 (0.776 to 0.837) in the validation cohort, respectively.

CONCLUSION: Radiomics signatures based on multiparametric MRI represent a potential and efficient alternative tool to evaluate the HER2 status in patients with breast cancer.}, } @article {pmid32709042, year = {2020}, author = {Narbe, U and Bendahl, PO and Aaltonen, K and Fernö, M and Forsare, C and Jørgensen, CLT and Larsson, AM and Rydén, L}, title = {The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast-Long-Term Prognostic Significance.}, journal = {Cells}, volume = {9}, number = {7}, pages = {}, pmid = {32709042}, issn = {2073-4409}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Cell Count ; Disease Progression ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Mucin-1/metabolism ; Neoplasm Metastasis ; Neoplastic Cells, Circulating/*pathology ; Prognosis ; Progression-Free Survival ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST.

MATERIALS AND METHODS: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS).

RESULTS: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST.

CONCLUSIONS: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.}, } @article {pmid32707685, year = {2020}, author = {Ali, I and Asif, M and Rehman, MRU and Khan, D and Yingge, H and Kim, SJ and Pu, Y and Yoo, SS and Lee, KY}, title = {A Highly Reliable, 5.8 GHz DSRC Wake-Up Receiver with an Intelligent Digital Controller for an ETC System.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {14}, pages = {}, pmid = {32707685}, issn = {1424-8220}, support = {2014R1A5A1011478//National Research Foundation of Korea/ ; }, abstract = {In this article, a highly reliable radio frequency (RF) wake-up receiver (WuRx) is presented for electronic toll collection (ETC) applications. An intelligent digital controller (IDC) is proposed as the final stage for improving WuRx reliability and replacing complex analog blocks. With IDC, high reliability and accuracy are achieved by sensing and ensuring the successive, configurable number of wake-up signal cycles before enabling power-hungry RF transceiver. The IDC and range communication (RC) oscillator current consumption is reduced by a presented self-hibernation technique during the non-wake-up period. For accommodating wake-up signal frequency variation and enhancing WuRx accuracy, a digital hysteresis is incorporated. To avoid uncertain conditions during poor and false wake-up, a watch-dog timer for IDC self-recovery is integrated. During wake-up, the digital controller consumes 34.62 nW power and draws 38.47 nA current from a 0.9 V supply. In self-hibernation mode, its current reduces to 9.7 nA. It is fully synthesizable and needs 809 gates for its implementation in a 130 nm CMOS process with a 94 × 82 µm[2] area. The WuRx measured power consumption is 2.48 µW, has -46 dBm sensitivity, and a 0.484 mm[2] chip area.}, } @article {pmid32702610, year = {2020}, author = {Taylor, S and Ayres, T and Jones, E}, title = {Enlightened hedonism? Independent drug checking amongst a group of ecstasy users.}, journal = {The International journal on drug policy}, volume = {83}, number = {}, pages = {102869}, doi = {10.1016/j.drugpo.2020.102869}, pmid = {32702610}, issn = {1873-4758}, mesh = {Affect ; *Drug Users ; Harm Reduction ; Humans ; *N-Methyl-3,4-methylenedioxyamphetamine ; *Pharmaceutical Preparations ; Philosophy ; }, abstract = {BACKGROUND: Research indicates that a body of ecstasy users across the globe employ 'home' drug testing technologies to learn more about the content of their drugs - a process referred to throughout this article as independent drug checking (IDC). Whilst a small number of studies offer accounts of this process, they do so through a narrow lens of harm reduction, potentially overlooking wider socio-cultural factors which may affect this. In response, this article draws on Slavoj Žižek's political theory of the cultural injunction to enjoy, situating IDC in the wider political economy of neoliberal consumer capitalism to contextualise and interpret its use as integral to pleasure and leisure.

METHODS: This empirical study documents the thoughts and experiences of a group of UK ecstasy users who independently use a privately owned drug-testing kit. Drawing on qualitative data generated through 20 semi-structured interviews, the article considers two research questions; what role did drug checking play in the group's drug journeys and leisure activities?; and is drug checking thought to be purposeful?

FINDINGS: For this group of ecstasy users, issues of safety and self-responsibility interweaved with the pursuit of pleasure as they sought to enjoy their drug consumption, but in a way that navigated potential harms. IDC therefore served to maximise pleasure via its 'guarantee' of a prolonged, enjoyable, authentic consumer experience whilst simultaneously safeguarding wellbeing via its premise of more responsible and controlled consumption practices.

CONCLUSION: IDC allowed this group of drug consumers to partake in 'enlightened hedonism' - demonstrating their conformity to the imperatives of capitalism and its social norms. Despite recognising the limitations of IDC and disclosing potentially harmful outcomes, the group's engagement with capitalist markets provided a belief that investment in your consumer experience can both improve it and make it safer - premises that belie the empirical reality.}, } @article {pmid32700071, year = {2020}, author = {Richards, D and Ayala, AA and Wu, Y and Middleton, LP}, title = {Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.}, journal = {Oncology and therapy}, volume = {8}, number = {1}, pages = {81-89}, pmid = {32700071}, issn = {2366-1089}, abstract = {INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.

METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.

RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3 years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.

CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.}, } @article {pmid32700069, year = {2020}, author = {Luveta, J and Parks, RM and Heery, DM and Cheung, KL and Johnston, SJ}, title = {Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy.}, journal = {Oncology and therapy}, volume = {8}, number = {1}, pages = {1-11}, pmid = {32700069}, issn = {2366-1089}, abstract = {Invasive lobular carcinoma comprises 10-15% of all breast cancers and is increasingly recognised as a distinct and understudied disease compared with the predominant histological subtype, invasive ductal carcinoma. Hallmarks of invasive lobular carcinoma include E-cadherin loss, leading to discohesive morphology with cells proliferating in single-file strands and oestrogen receptor positivity, with favourable response to endocrine therapy. This review summarises the distinct histological and molecular features of invasive lobular carcinoma with focus on diagnostic challenges and the impact on surgical management and medical therapy. Emphasis is placed on recent advances in our understanding of the unique molecular biology of lobular breast cancer and how this is optimising our therapy approach in the clinic.}, } @article {pmid32694843, year = {2019}, author = {Seitz, S and Kwon, Y and Hartleben, G and Jülg, J and Sekar, R and Krahmer, N and Najafi, B and Loft, A and Gancheva, S and Stemmer, K and Feuchtinger, A and Hrabe de Angelis, M and Müller, TD and Mann, M and Blüher, M and Roden, M and Berriel Diaz, M and Behrends, C and Gilleron, J and Herzig, S and Zeigerer, A}, title = {Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.}, journal = {Nature metabolism}, volume = {1}, number = {10}, pages = {1009-1026}, pmid = {32694843}, issn = {2522-5812}, mesh = {Adiposity ; Adult ; Animals ; Autophagy ; Blood Glucose/*metabolism ; Cholesterol/blood ; Female ; Homeostasis ; Humans ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Liver/*metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism ; Up-Regulation ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.}, } @article {pmid32693034, year = {2021}, author = {Bhagat, R and Swanson, SJ and Hammer, MM and Mallidi, HR and White, A}, title = {Multimodality Curative Treatment of IIIA/T4 Lung Adenocarcinoma.}, journal = {The Annals of thoracic surgery}, volume = {111}, number = {2}, pages = {e73-e75}, doi = {10.1016/j.athoracsur.2020.05.122}, pmid = {32693034}, issn = {1552-6259}, mesh = {Adenocarcinoma of Lung/diagnosis/*therapy ; Adult ; Antineoplastic Agents/*therapeutic use ; Combined Modality Therapy/methods ; Female ; Humans ; Lung Neoplasms/diagnosis/*therapy ; Magnetic Resonance Imaging ; Neoplasm Invasiveness ; *Neoplasm Staging ; Pneumonectomy/*methods ; Tomography, X-Ray Computed ; }, abstract = {We present a 41-year-old female smoker with concurrent invasive ductal carcinoma of the right breast and stage IIIA (T4N0M0) adenocarcinoma of the left lung requiring neoadjuvant chemoradiation followed by left pneumonectomy. We use this report as an educational work to show how multidisciplinary clinical decisions can be made to give way to successful treatment of a highly complex lung adenocarcinoma. Specifically, we show curative radical treatment of T4 disease and successful radical intervention of radiation-induced cardiac complications to achieve a comprehensive and curative treatment.}, } @article {pmid32688099, year = {2020}, author = {Maaravi, Y and Heller, B}, title = {Not all worries were created equal: the case of COVID-19 anxiety.}, journal = {Public health}, volume = {185}, number = {}, pages = {243-245}, pmid = {32688099}, issn = {1476-5616}, mesh = {Adult ; Anxiety/*epidemiology ; COVID-19 ; Coronavirus Infections/epidemiology/*psychology ; Cross-Sectional Studies ; Family/psychology ; Female ; Humans ; Interpersonal Relations ; Male ; *Pandemics ; Pneumonia, Viral/epidemiology/*psychology ; Psychological Theory ; Sex Distribution ; Socioeconomic Factors ; Surveys and Questionnaires ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: The objective of this study was to investigate possible differences in COVID-19-related anxiety based on previous theories in social psychology.

STUDY DESIGN: Cross-sectional online questionnaire delivered via the crowdworking platform.

METHODS: Four-hundred and seven (120 men and 287 women) adults (aged >18 years) from the United Kingdom answered the State-Trait Anxiety Inventory 'in light of the COVID-19 situation', followed by three health and three financial anxiety items.

RESULTS: Our findings imply that women are more anxious than men, people are more anxious about others than about themselves, their anxiety about relatives is higher than about strangers, and anxiety about health is higher than about financial issues.

CONCLUSIONS: We suggest that these preliminary findings should be further investigated to help policymakers improve both their treatment of pandemic-related anxiety and their messages.}, } @article {pmid32686908, year = {2020}, author = {Ma, L and Qi, L and Li, S and Yin, Q and Liu, J and Wang, J and She, C and Li, P and Liu, Q and Wang, X and Li, W}, title = {Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.}, journal = {Thoracic cancer}, volume = {11}, number = {9}, pages = {2493-2505}, pmid = {32686908}, issn = {1759-7714}, support = {81702481//National Natural Science Foundation of China/ ; 15JCQNJC44800//Natural Science Foundation of Tianjin City/ ; 18JCYBJC27600//Natural Science Foundation of Tianjin City/ ; }, mesh = {Brain Neoplasms/*enzymology/*secondary ; Breast Neoplasms/*complications/*enzymology/pathology ; Female ; Histone Deacetylases/*metabolism ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.

METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.

RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.

CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.

KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.}, } @article {pmid32685081, year = {2020}, author = {Yoo, K and Choi, RY and Sun, J and Veselis, C and Kamat, B and Kumaran, M and Agosto, O and Maresky, HS}, title = {Incidental COVID-19 in the radiology department: Radiographic findings of COVID-19 in asymptomatic patient undergoing CT staging for breast cancer.}, journal = {Radiology case reports}, volume = {15}, number = {9}, pages = {1614-1617}, pmid = {32685081}, issn = {1930-0433}, abstract = {A 59-year-old incarcerated woman who was diagnosed with invasive ductal carcinoma in 2016 was brought in for evaluation of the breast cancer. Upon evaluation of the computed tomography chest for breast cancer restaging, diffuse bilateral ground glass opacities and a reverse halo sign in the right lower lobe concerning for atypical viral pneumonia were discovered. The patient was afebrile, had an oxygen saturation of 100%, and denied chest pain as well as shortness of breath. On physical exam, she exhibited decreased breath sounds bilaterally and expiratory wheezing. She later received a COVID-19 test, which came back positive. Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also known as COVID-19) may remain asymptomatic in the initial phase, leading to under-recognition and incidental detection on procedures for standard clinical indications. Hospitals, in particular diagnostic imaging services, should prepare accordingly in regard to health precautions while keeping in mind the potential discrepancies between clinical presentation and resultant radiologic patterns. This awareness should be heightened in patients at higher risk (ie, prisoners). Furthermore, by acting upon the incidental detection of this virus during its early stages, subsequent steps could help prevent the spread of the virus.}, } @article {pmid32680923, year = {2021}, author = {Ulaner, GA and Jhaveri, K and Chandarlapaty, S and Hatzoglou, V and Riedl, CC and Lewis, JS and Mauguen, A}, title = {Head-to-Head Evaluation of [18]F-FES and [18]F-FDG PET/CT in Metastatic Invasive Lobular Breast Cancer.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {62}, number = {3}, pages = {326-331}, pmid = {32680923}, issn = {1535-5667}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Estradiol/*analogs & derivatives ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Positron Emission Tomography Computed Tomography/*methods ; Retrospective Studies ; }, abstract = {Invasive lobular carcinoma (ILC) demonstrates lower conspicuity on [18]F-FDG PET than the more common invasive ductal carcinoma. Other molecular imaging methods may be needed for evaluation of this malignancy. As ILC is nearly always (95%) estrogen receptor (ER)-positive, ER-targeting PET tracers such as 16α-[18]F-fluoroestradiol ([18]F-FES) may have value. We reviewed prospective trials at Memorial Sloan Kettering Cancer Center using [18]F-FES PET/CT to evaluate metastatic ILC patients with synchronous [18]F-FDG and [18]F-FES PET/CT imaging, which allowed a head-to-head comparison of these 2 PET tracers. Methods: Six prospective clinical trials using [18]F-FES PET/CT in patients with metastatic breast cancer were performed at Memorial Sloan Kettering Cancer Center from 2008 to 2019. These trials included 92 patients, of whom 14 (15%) were of ILC histology. Seven of 14 patients with ILC had [18]F-FDG PET/CT performed within 5 wk of the research [18]F-FES PET/CT and no intervening change in management. For these 7 patients, the [18]F-FES and [18]F-FDG PET/CT studies were analyzed to determine the total number of tracer-avid lesions, organ systems of involvement, and SUVmax of each organ system for both tracers. Results: In the 7 comparable pairs of scans, there were a total of 254 [18]F-FES-avid lesions (SUVmax, 2.6-17.9) and 111 [18]F-FDG-avid lesions (SUVmax, 3.3-9.9) suggestive of malignancy. For 5 of 7 (71%) ILC patients, [18]F-FES PET/CT detected more metastatic lesions than [18]F-FDG PET/CT. In the same 5 of 7 patients, the SUVmax of [18]F-FES-avid lesions was greater than the SUVmax of [18]F-FDG-avid lesions. One patient had [18]F-FES-avid metastases with no corresponding [18]F-FDG-avid metastases. There were no patients with [18]F-FDG-avid distant metastases without [18]F-FES-avid distant metastases, although in one patient liver metastases were evident on [18]F-FDG but not on [18]F-FES PET. Conclusion:[18]F-FES PET/CT compared favorably with [18]F-FDG PET/CT for detection of metastases in patients with metastatic ILC. Larger prospective trials of [18]F-FES PET/CT in ILC should be considered to evaluate ER-targeted imaging for clinical value in patients with this histology of breast cancer.}, } @article {pmid32678033, year = {2020}, author = {Shete, A and Dhayarkar, S and Dhamanage, A and Kulkarni, S and Ghate, M and Sangle, S and Medhe, U and Verma, V and Rajan, S and Hattori, T and Gangakhedkar, R}, title = {Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings.}, journal = {AIDS research and therapy}, volume = {17}, number = {1}, pages = {43}, pmid = {32678033}, issn = {1742-6405}, mesh = {Adult ; Anti-Retroviral Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Biomarkers/blood ; Cross-Sectional Studies ; Female ; Galectins/*blood ; HIV Infections/blood/*diagnosis/*drug therapy ; Health Resources ; Humans ; Male ; Middle Aged ; Viral Load ; Viremia/*diagnosis ; Young Adult ; }, abstract = {BACKGROUND: Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services. Hence, cheaper surrogate markers of viremia are desired to reduce overall cost of management of HIV infected patients.

METHODS: We enrolled aviremic (n = 63, M:F = 31:32) and viremic (n = 43, M:F = 21:22) HIV infected patients at 1 year after ART initiation. Viremic individuals were identified as those having a plasma VL of more than 1000 copies/µl and aviremic individuals as less than 40 copies/µl. The study participants also included immuno-virologically discordant patients as they demonstrate differential degrees of immune-reconstitution and are likely to harbour concomitant infections influencing levels of immune-activation markers screened as the surrogate markers. Immune activation markers viz. plasma hs-CRP, soluble-CD14 and Galectin-9 levels were estimated by ELISA, IL-6 by luminex assay and percentages of CD38+ CD8+ cells were determined by flow cytometry. The levels were compared between viremic and aviremic patients and correlated with plasma viral load. Receiver operated curve (ROC) analysis was done for plasma Galectin-9 levels.

RESULTS: Viremic patients had significantly higher levels of Galectin-9 and %CD38+ CD8+ cells (p values < 0.0001) than aviremic patients. Levels of the other activation markers did not differ between viremic and aviremic individuals. Galectin-9 levels (r = 0.76) and %CD38+ CD8+ cells (r = 0.39) correlated positively with VL. Area under curve for Galectin-9 levels for distinguishing between viremic and aviremic individuals was 0.98. Youden index, sensitivity, specificity, positive predictive value and negative predictive value for Galectin-9 levels were 0.87, 0.97, 0.90, 0.87 and 0.98, respectively, at the cut-off value of 5.79 ng/ml.

CONCLUSIONS: Plasma Galectin-9 levels could identify viremic individuals with sensitivity and specificity of more than 90%. Thus, they showed a potential to serve as a surrogate marker of viremia in HIV infected patients on ART and would have cost implications on HIV management especially in resource-limited settings. However, the findings need to be confirmed in the patients on ART for different durations of time.}, } @article {pmid32678029, year = {2020}, author = {Adachi, T and Machida, Y and Fukuma, E and Tateishi, U}, title = {Fluorodeoxyglucose positron emission tomography/computed tomography findings after percutaneous cryoablation of early breast cancer.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {20}, number = {1}, pages = {49}, pmid = {32678029}, issn = {1470-7330}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/surgery ; Cryosurgery/adverse effects/*methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnostic imaging ; Positron Emission Tomography Computed Tomography/*methods/standards ; Postoperative Complications/*diagnostic imaging ; Radiopharmaceuticals ; }, abstract = {BACKGROUND: To document [18]F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings after percutaneous cryoablation for early breast cancer.

METHODS: Data of 193 consecutive patients who had undergone cryoablation for invasive ductal carcinoma or ductal carcinoma in situ ≤ 15 mm without a history of ipsilateral breast cancer, synchronous ipsilateral lesion, and with estrogen receptor positive/human epidermal growth factor 2 negative were enrolled. The imaging characteristics of the treated areas were evaluated and classified on CT images as one of two types: fatty mass or non-fatty mass type. The maximum standardized uptake value (SUVmax) of the initial post-cryoablation PET/CT, the CT type of the treated area and selected clinical factors (age, menopausal status, lesion area, breast density, timing of PET/CT) were retrospectively evaluated.

RESULTS: The median interval between cryoablation and the initial post-cryoablation PET/CT was 12 months. The median SUVmax of the treated area was 1.36. The CT findings of the treated area were classified as fatty mass type (n = 137, 71.0%) or non-fatty mass type (n = 56, 29.0%). The treated areas of patients with lower breast density, of older age, post-menopausal status, and lower radiation dose were significantly more likely to be of fatty mass type (P < 0.001). Non-fatty mass type averaged a significantly higher SUVmax than did fatty mass type.

CONCLUSIONS: Post-cryoablation PET/CT findings are of fatty or non-fatty mass type. A non-fatty appearance, which can show higher SUVmax, does not necessarily denote recurrence.}, } @article {pmid32672524, year = {2021}, author = {Madjar, N and Sarel-Mahlev, E and Brunstein Klomek, A}, title = {Depression Symptoms as Mediator Between Adolescents' Sense of Loneliness at School and Nonsuicidal Self-Injury Behaviors.}, journal = {Crisis}, volume = {42}, number = {2}, pages = {144-151}, doi = {10.1027/0227-5910/a000702}, pmid = {32672524}, issn = {2151-2396}, mesh = {Adolescent ; Cross-Sectional Studies ; Depression ; Female ; Humans ; *Loneliness ; Male ; Schools ; *Self-Injurious Behavior ; }, abstract = {Background: Previous studies indicated that perception of school experiences (i.e., teachers' psychological support and perceived peer climate) is associated with nonsuicidal self-injury (NSSI) behaviors among adolescents. Aims: The purpose of the current study was to explore whether depression symptoms mediate the relationship between sense of loneliness in school and NSSI behaviors among adolescents. Method: The sample included high-school students (N = 306; 51.6% girls) who completed surveys assessing their subjective sense of loneliness (feeling lonely, spending their time alone in school, and reporting a small number of friends), depression symptoms, and NSSI behaviors. Results: Multiple-group structural equation modeling, stratified by gender, supported the hypothesized model. Sense of loneliness was associated with depression symptoms, which in turn were associated with NSSI. Positive school attitudes were associated with depression symptoms only for girls. Results were robust when controlling for the relationships with parents. Limitations: The study is based on cross-sectional data, which limits the ability to make causal conclusions, and the instruments are based on self-report scales. Conclusion: Mental health professional are advised to note the significant role of subjective sense of loneliness in school as a possible risk factor for depression symptoms, which may be associated with NSSI behaviors.}, } @article {pmid32668059, year = {2020}, author = {Arciero, CA and Diehl, AH and Liu, Y and Sun, Q and Gillespie, T and Li, X and Subhedar, P}, title = {Triple-negative apocrine carcinoma: A rare pathologic subtype with a better prognosis than other triple-negative breast cancers.}, journal = {Journal of surgical oncology}, volume = {122}, number = {6}, pages = {1232-1239}, doi = {10.1002/jso.26129}, pmid = {32668059}, issn = {1096-9098}, support = {P30CA138292/CA/NCI NIH HHS/United States ; P30CA138292/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apocrine Glands/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Cohort Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; SEER Program ; Survival Rate ; Triple Negative Breast Neoplasms/*mortality/pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND AND METHODS: Apocrine adenocarcinoma is a rare subtype of breast cancer. We sought to compare the characteristics and survival of patients diagnosed with triple-negative apocrine adenocarcinoma to those of patients diagnosed with triple-negative invasive ductal carcinoma. Utilizing data from the National Cancer Database between 2004 and 2013, 70 524 eligible female patients with triple-negative breast cancer were identified including 566 patients with apocrine adenocarcinomas and 69 958 patients with invasive ductal carcinoma. Descriptive statistics for each variable were reported. A comparison of each covariate between the study cohorts was assessed in univariate and multivariate analysis. Cox proportional models were used to calculate hazard ratios. Additionally, the propensity score matching method was implemented to reduce treatment selection bias.

RESULTS: Patients with triple-negative apocrine tumors were more likely to be older, Caucasian, and have smaller, moderately to well-differentiated tumors. Multivariable analysis noted a significantly improved survival for patients with triple-negative apocrine carcinoma (TNAC) vs triple-negative invasive ductal carcinoma (TNBC) (hazard ratio [HR] 0.65 [95% confidence interval [CI] [0.53-0.81], P = 0 < .001). Propensity score matching analysis confirmed a significant difference in overall survival for patients with TNAC in comparison to TNBC (HR 0.79 [95% CI [0.63-1.00], P = .05).

DISCUSSION: Triple-negative apocrine adenocarcinomas have a modestly improved long-term survival when compared with triple-negative invasive ductal cancers.}, } @article {pmid32665190, year = {2020}, author = {Escott, CE and Zaenger, D and Switchencko, JM and Lin, JY and Abugideiri, M and Arciero, CA and Pfister, NT and Xu, KM and Meisel, JL and Subhedar, P and Torres, M and Curran, WJ and Patel, PR}, title = {The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {e701-e710}, pmid = {32665190}, issn = {1938-0666}, support = {P30 CA138292/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/mortality/pathology/*therapy ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental/*statistics & numerical data ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant/statistics & numerical data ; SEER Program/statistics & numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.

MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.

RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043).

CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.}, } @article {pmid32662684, year = {2020}, author = {Shan, Z and Liu, L and Shen, J and Hao, H and Zhang, H and Lei, L and Liu, F and Wang, Z}, title = {Enhanced UV Resistance Role of Death Domain-Associated Protein in Human MDA-MB-231 Breast Cancer Cells by Regulation of G2 DNA Damage Checkpoint.}, journal = {Cell transplantation}, volume = {29}, number = {}, pages = {963689720920277}, pmid = {32662684}, issn = {1555-3892}, mesh = {Adult ; Breast Neoplasms/*genetics ; Cell Proliferation ; DNA Damage/*genetics ; Death Domain/*genetics ; Female ; G2 Phase Cell Cycle Checkpoints ; Humans ; Immunohistochemistry/*methods ; Middle Aged ; }, abstract = {PURPOSE: Death domain-associated protein (DAXX) is a multifunctional nuclear protein involved in apoptosis, transcription, deoxyribonucleic acid damage response, and tumorigenesis. However, the role of DAXX in breast cancer development and progression remains elusive. In this study, we examined the expression patterns and function of DAXX in human breast cancer samples and cell lines.

METHODS: Immunohistochemistry was used to analyze the expression and localization patterns of DAXX. Additionally, we investigated whether DAXX played an intrinsic role in the cellular response to damage induced by ultraviolet (UV) irradiation in MDA-MB-231 breast cancer cells (isolated at M D Anderson from a pleural effusion of a patient with invasive ductal carcinoma).

RESULTS: Our results showed that nucleus size, chromatin organization, and DAXX localization were altered in breast cancer tissues compared with those in control tissues. Compared with cytoplasmic and nuclear expression in benign breast tissues, DAXX was colocalized with promyelocytic leukemia in nuclei with a granular distribution. Endogenous DAXX messenger ribonucleic acid levels were upregulated upon UV radiation in MDA-MB-231 cells. DAXX-deficient cells tended to be more sensitive to irradiation than control cells. Conversely, DAXX-overexpressing cells exhibited reduced phosphorylated histone H2AX (γ-H2AX) accumulation, increased cell survival, and resistance to UV-induced damage. The protective effects of DAXX may be related to the activation of the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (ATM-CHK2)-cell division cycle 25c (CDC25c) signaling pathways in Gap2/Mitosis (G2/M) checkpoint and ultimately cell cycle arrest at G2/M phase.

CONCLUSIONS: Taken together, these results suggested that DAXX may be an essential component in breast cancer initiation, malignant progression, and radioresistance.}, } @article {pmid32661669, year = {2021}, author = {Rooper, LM and Thompson, LDR and Gagan, J and Oliai, BR and Weinreb, I and Bishop, JA}, title = {Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion.}, journal = {Head and neck pathology}, volume = {15}, number = {1}, pages = {179-185}, pmid = {32661669}, issn = {1936-0568}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Ductal/genetics/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Parotid Neoplasms/genetics/*pathology ; }, abstract = {Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.}, } @article {pmid32661241, year = {2020}, author = {Tasdemir, N and Ding, K and Savariau, L and Levine, KM and Du, T and Elangovan, A and Bossart, EA and Lee, AV and Davidson, NE and Oesterreich, S}, title = {Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {11487}, pmid = {32661241}, issn = {2045-2322}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; 5F30CA203154/NH/NIH HHS/United States ; K99CA237736/NH/NIH HHS/United States ; 1F31CA203055-01/NH/NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA203055/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; }, mesh = {Autoantigens/genetics ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Inhibitor of Differentiation Protein 1/genetics ; Inhibitor of Differentiation Proteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/genetics ; Phosphatidylinositol 3-Kinases/genetics ; *Proteomics ; Proto-Oncogene Proteins c-akt/genetics ; Ribosomal Protein S6 Kinases, 90-kDa/genetics ; Signal Transduction/genetics ; Transcriptome/*genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.}, } @article {pmid32660025, year = {2020}, author = {Palacios, T and Vitetta, L and Coulson, S and Madigan, CD and Lam, YY and Manuel, R and Briskey, D and Hendy, C and Kim, JN and Ishoey, T and Soto-Giron, MJ and Schott, EM and Toledo, G and Caterson, ID}, title = {Targeting the Intestinal Microbiota to Prevent Type 2 Diabetes and Enhance the Effect of Metformin on Glycaemia: A Randomised Controlled Pilot Study.}, journal = {Nutrients}, volume = {12}, number = {7}, pages = {}, pmid = {32660025}, issn = {2072-6643}, mesh = {Aged ; Bacteroidetes/physiology ; Blood Glucose/*analysis ; Butyrates/blood ; Diabetes Mellitus, Type 2/*blood ; Fatty Acids, Volatile/blood ; Female ; Firmicutes/physiology ; *Gastrointestinal Microbiome/drug effects ; Haptoglobins ; Humans ; Hypoglycemic Agents/*administration & dosage ; Insulin Resistance ; Male ; Metabolic Networks and Pathways/drug effects ; Metformin/*administration & dosage ; Middle Aged ; Pilot Projects ; Prediabetic State/blood ; Probiotics/*administration & dosage/adverse effects/pharmacology ; Protein Precursors/blood ; Proteobacteria/physiology ; }, abstract = {Early treatment may prevent or delay the onset of type 2 diabetes mellitus (T2DM) in individuals who are at high risk. Lifestyle interventions and the hypoglycemic drug metformin have been shown to reduce T2DM incidence. The effectiveness of such interventions may be enhanced by targeting environmental factors such as the intestinal microbiota, which has been proven to predict the response to lifestyle interventions and play a part in mediating the glucose-lowering effects of metformin. Shifts in the intestinal microbiota "towards a more balanced state" may promote glucose homeostasis by regulating short-chain fatty acids' production. This study aimed to investigate the safety and effect of a multi-strain probiotic on glycemic, inflammatory, and permeability markers in adults with prediabetes and early T2DM and to assess whether the probiotic can enhance metformin's effect on glycaemia. A randomised controlled pilot study was conducted in 60 adults with a BMI ≥ 25 kg/m[2] and with prediabetes or T2DM (within the previous 12 months). The participants were randomised to a multi-strain probiotic (L. plantarum, L. bulgaricus, L. gasseri, B. breve, B. animalis sbsp. lactis, B. bifidum, S. thermophilus, and S. boulardii) or placebo for 12 weeks. Analyses of the primary outcome (fasting plasma glucose) and secondary outcomes, including, but not limited to, circulating lipopolysaccharide, zonulin, and short chain fatty acids and a metagenomic analysis of the fecal microbiome were performed at baseline and 12 weeks post-intervention. The results showed no significant differences in the primary and secondary outcome measures between the probiotic and placebo group. An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group. Probiotics may act as an adjunctive to metformin by increasing the production of butyrate, which may consequently enhance glucose management.}, } @article {pmid32658738, year = {2020}, author = {Zeng, Y and Zhang, J}, title = {A machine learning model for detecting invasive ductal carcinoma with Google Cloud AutoML Vision.}, journal = {Computers in biology and medicine}, volume = {122}, number = {}, pages = {103861}, doi = {10.1016/j.compbiomed.2020.103861}, pmid = {32658738}, issn = {1879-0534}, mesh = {*Carcinoma, Ductal ; Humans ; *Machine Learning ; Neural Networks, Computer ; }, abstract = {OBJECTIVES: This study is aimed to assess the feasibility of AutoML technology for the identification of invasive ductal carcinoma (IDC) in whole slide images (WSI).

METHODS: The study presents an experimental machine learning (ML) model based on Google Cloud AutoML Vision instead of a handcrafted neural network. A public dataset of 278,124 labeled histopathology images is used as the original dataset for the model creation. In order to balance the number of positive and negative IDC samples, this study also augments the original public dataset by rotating a large portion of positive image samples. As a result, a total number of 378,215 labeled images are applied.

RESULTS: A score of 91.6% average accuracy is achieved during the model evaluation as measured by the area under precision-recall curve (AuPRC). A subsequent test on a held-out test dataset (unseen by the model) yields a balanced accuracy of 84.6%. These results outperform the ones reported in the earlier studies. Similar performance is observed from a generalization test with new breast tissue samples we collected from the hospital.

CONCLUSIONS: The results obtained from this study demonstrate the maturity and feasibility of an AutoML approach for IDC identification. The study also shows the advantage of AutoML approach when combined at scale with cloud computing.}, } @article {pmid32652799, year = {2020}, author = {Xu, C and Markova, M and Seebeck, N and Loft, A and Hornemann, S and Gantert, T and Kabisch, S and Herz, K and Loske, J and Ost, M and Coleman, V and Klauschen, F and Rosenthal, A and Lange, V and Machann, J and Klaus, S and Grune, T and Herzig, S and Pivovarova-Ramich, O and Pfeiffer, AFH}, title = {High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {40}, number = {12}, pages = {2982-2997}, doi = {10.1111/liv.14596}, pmid = {32652799}, issn = {1478-3231}, mesh = {Autophagy ; Diet ; Diet, High-Fat ; *Diet, High-Protein ; *Diet, Protein-Restricted ; Dietary Proteins ; Fibroblast Growth Factors ; Humans ; Liver ; }, abstract = {BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low- (LP) or high-protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved.

METHODS: 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500-1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery.

RESULTS: IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA-seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β-oxidation genes did not increase in the HP group.

CONCLUSIONS: HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.}, } @article {pmid32652097, year = {2020}, author = {Heimler, B and Amedi, A}, title = {Are critical periods reversible in the adult brain? Insights on cortical specializations based on sensory deprivation studies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {116}, number = {}, pages = {494-507}, doi = {10.1016/j.neubiorev.2020.06.034}, pmid = {32652097}, issn = {1873-7528}, mesh = {Adult ; Auditory Perception ; Brain ; Humans ; Neuronal Plasticity ; *Sensory Deprivation ; *Visual Cortex ; }, abstract = {We review here studies with visual and auditory deprived/recovery populations to argue for the need of a redefinition of the crucial role of unisensory-specific experiences during critical periods (CPs) on the emergence of sensory specializations. Specifically, we highlight that these studies, with emphasis on results with congenitally blind adults using visual sensory-substitution devices, consistently document that typical specializations (e.g., in visual cortex) could arise also in adulthood via other sensory modalities (e.g., audition), even after relatively short (tailored) trainings. Altogether, these studies suggest that 1) brain specializations are driven by sensory-independent computations rather than by unisensory-specific inputs and that 2) specific computation-oriented trainings, even if executed during adulthood, can guide the sensory brain to display/recover, core properties of brain specializations. We thus introduce here the concept of a reversible plasticity gradient, namely that brain plasticity spontaneously decreases with age in line with CPs theory, but it nonetheless can be reignited across the lifespan, even without any exposure to unisensory (e.g., visual) experiences during childhood, thus diverging dramatically from CPs assumptions.}, } @article {pmid32650989, year = {2020}, author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Patocskai, E and Nouraie, M}, title = {Oncoplastic Repair in Breast Conservation: Comprehensive Evaluation of Techniques and Oncologic Outcomes of 937 Patients.}, journal = {Clinical breast cancer}, volume = {20}, number = {6}, pages = {511-519}, doi = {10.1016/j.clbc.2020.05.016}, pmid = {32650989}, issn = {1938-0666}, mesh = {Adult ; Breast/pathology/surgery ; Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/statistics & numerical data ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Iran/epidemiology ; Mammaplasty/*adverse effects/methods/statistics & numerical data ; Margins of Excision ; Mastectomy, Segmental/*adverse effects/statistics & numerical data ; Middle Aged ; Neoadjuvant Therapy/methods/statistics & numerical data ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Reoperation/statistics & numerical data ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast-conserving surgery, especially with oncoplastic breast surgery (OBS), is becoming the standard of care in the surgical management of breast cancer. We investigated the applied technique of OBS and oncologic outcomes in a large series of patients.

PATIENTS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS. Early and late postoperative complications, oncologic outcomes, and follow-up data were documented.

RESULTS: Nine hundred thirty-seven patients with a mean ± standard deviation age of 48.1 ± 11.3 underwent OBS. Most of the patients were diagnosed with early-stage disease, of which the most common pathology was invasive ductal carcinoma (83.3%). Lateral oncoplasty was the most commonly used OBS technique (324 cases, 34.6%). The most common complication was seroma formation. Reduction-type OBS technique had the highest rate of complications (13.1%). Thirty-four patients (5.4%) experienced local recurrence, with a median recurrence time of 26.4 months. Nine patients (1.3%) died from cancer recurrence.

CONCLUSION: OBS is a safe procedure with minor complications and good oncologic outcomes. These techniques can be applied to most patients who are candidates for breast-conserving surgery.}, } @article {pmid32645702, year = {2020}, author = {Zhang, M and Meng, X and Guo, C and Liu, J and Xing, Z and Wang, X and Wang, X}, title = {Clinicopathological Relevance and Prognostic Value of Androgen Receptor in Mammary Paget's Disease with Underlying Invasive Ductal Carcinoma.}, journal = {Oncology research and treatment}, volume = {43}, number = {7-8}, pages = {346-353}, doi = {10.1159/000507893}, pmid = {32645702}, issn = {2296-5262}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Estrogen Receptor alpha/*metabolism ; Female ; Humans ; Lymph Nodes/metabolism/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Paget's Disease, Mammary/metabolism/*pathology ; Prognosis ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Mammary Paget's disease (MPD) is a rare cutaneous manifestation. Epidemiologically, more than half of the MPD patients concurrently have underlying invasive ductal carcinoma (MPD-IDC), and their prognosis remains poor despite multimodal treatments of breast cancer have markedly improved patients' survival. Accordingly, it is crucial to seek out novel therapeutic targets of MPD-IDC. As an emerging biological marker, the value of androgen receptor (AR) in MPD-IDC is inconsistent. Our objectives were to investigate the associations between AR and clinicopathological factors, and to explore its prognostic value in MPD-IDC.

METHODS: We retrospectively analyzed data from 103 MPD-IDC patients, and immunohistochemical staining was used to determine their AR statuses.

RESULTS: AR was expressed in 44 patients (42.7%), and AR expression was significantly correlated with body mass index (BMI) (p = 0.038) and axillary lymph node (ALN) status (p = 0.025). Kaplan-Meier curves showed that AR positivity was significantly associated with better overall survival (OS) in MPD-IDC patients (p = 0.019) and estrogen receptor-negative MPD-IDC patients (p = 0.039). Multivariate Cox regression analysis revealed that AR was not an independent prognostic indicator of disease-free survival (DFS) or OS in MPD-IDC patients (p = 0.395 and p = 0.073, respectively).

CONCLUSIONS: In contrast to AR-negative tumors, patients with AR-positive ones were more likely to have lower BMI, no ALN metastasis, and better OS. AR-targeted treatments for MPD-IDC may add to existing therapeutic approaches to improve their effectiveness.}, } @article {pmid32638169, year = {2021}, author = {Zhang, M and Wu, K and Zhang, P and Wang, M and Bai, F and Chen, H}, title = {Breast-Conserving Surgery is Oncologically Safe for Well-Selected, Centrally Located Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {28}, number = {1}, pages = {330-339}, pmid = {32638169}, issn = {1534-4681}, support = {201940391//Shanghai Municipal Health Bureau/ ; }, mesh = {Aged ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Lobular/pathology/surgery ; Female ; Humans ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Staging ; Retrospective Studies ; SEER Program ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the long-term survival outcomes of breast-conserving surgery (BCS) in centrally located breast cancer (CLBC) compared with mastectomy in CLBC and BCS in non-CLBC, based on the Surveillance, Epidemiology, and End Results (SEER) database.

METHODS: Female patients aged < 80 years with unilateral T1-T2 invasive ductal or lobular breast cancer undergoing BCS or mastectomy were enrolled. The differences in clinical-pathological characteristics were evaluated using Chi square tests. Multivariate logistic regression was used to measure the relationship between predictive variables and performing BCS in CLBC. Survival outcomes were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. To overcome the effects of baseline differences on survival outcome in patients treated with BCS in the central and upper-outer locations, a 1:1 ratio propensity score matching method was performed.

RESULTS: Overall, among 16,522 CLBC patients, 7982 cases (48.3%) underwent BCS between 1998 and 2015. Factors such as older age, Black race, invasive ductal carcinoma (IDC), grade I, small tumor size, none or limited lymph node metastasis, positive progesterone receptor status, and receiving chemotherapy were independently correlated with BCS. BCS was an independent favorable prognostic factor among CLBC patients, based on multivariate Cox analysis. It was also shown that CLBC had similar survival outcomes compared with tumors in the upper-outer quadrant, and had a better breast cancer-specific survival compared with tumors in the lower quadrants, based on multivariate Cox analysis.

CONCLUSIONS: BCS should be an acceptable and preferable alternative to mastectomy for well-selected, early-stage T1 or T2 CLBC.}, } @article {pmid32637252, year = {2020}, author = {Jones, B and Thomas, G and Westreich, J and Nofech-Mozes, S and Vitkin, A and Khorasani, M}, title = {Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.}, journal = {Biomedical optics express}, volume = {11}, number = {6}, pages = {3246-3262}, pmid = {32637252}, issn = {2156-7085}, abstract = {As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.}, } @article {pmid32636849, year = {2020}, author = {Siegers, GM and Dutta, I and Kang, EY and Huang, J and Köbel, M and Postovit, LM}, title = {Aberrantly Expressed Embryonic Protein NODAL Alters Breast Cancer Cell Susceptibility to γδ T Cell Cytotoxicity.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1287}, pmid = {32636849}, issn = {1664-3224}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Intraepithelial Lymphocytes/*immunology ; Middle Aged ; Nodal Protein/*immunology/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Triple Negative Breast Neoplasms/*immunology/metabolism ; Tumor Escape/*immunology ; Tumor Microenvironment/*immunology ; }, abstract = {Gamma delta (γδ) T cells kill transformed cells, and increased circulating γδ T cells levels correlate with improved outcome in cancer patients; however, their function within the breast tumor microenvironment (TME) remains controversial. As tumors progress, they begin to express stem-cell associated proteins, concomitant with the emergence of therapy resistant metastatic disease. For example, invasive breast cancers often secrete the embryonic morphogen, NODAL. NODAL has been shown to promote angiogenesis, therapy resistance and metastasis in breast cancers. However, to date, little is known about how this secreted protein may interact with cells in the TME. Herein we explore how NODAL in the TME may influence γδ T cell function. We have assessed the proximity of γδ T cells to NODAL in a cohort of triple negative breast tumors. In all cases in which γδ T cells could be identified in these tumors, γδ T cells were found in close proximity to NODAL-expressing tumor cells. Migration of γδ and αβ T cells was similar toward MDA-MB-231 cells in which NODAL had been knocked down (shN) and MDA-MB-231 scrambled control cells (shC). Furthermore, Vδ1 γδ T cells did not migrate preferentially toward conditioned medium from these cell lines. While 24-h exposure to NODAL did not impact CD69, PD-1, or T cell antigen receptor (TCR) expression on γδ T cells, long term exposure resulted in decreased Vδ2 TCR expression. Maturation of γδ T cells was not significantly influenced by NODAL stimulation. While neither short- nor long-term NODAL stimulation impacted the ability of γδ T cells to kill MCF-7 breast cancer cells, the absence of NODAL resulted in greater sensitivity of targets to γδ T cell cytotoxicity, while overexpression of NODAL conferred resistance. This appeared to be at least in part due to an inverse correlation between NODAL and surface MICA/B expression on breast cancer target lines. As such, it appears that NODAL may play a role in strategies employed by breast cancer cells to evade γδ T cell targeting, and this should be considered in the development of safe and effective γδ T cell immunotherapies.}, } @article {pmid32636177, year = {2020}, author = {Sadeh-Sharvit, S and Runfola, CD and Welch, HA and Gibbs, EL and Dickens, CE and Lock, J and Safer, DL}, title = {Parent-based prevention after parental weight loss surgery: a pilot case-series trial.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {16}, number = {9}, pages = {1321-1327}, doi = {10.1016/j.soard.2020.05.016}, pmid = {32636177}, issn = {1878-7533}, mesh = {*Bariatric Surgery ; Child ; *Feeding Behavior ; Humans ; Obesity ; Parenting ; Parents ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Overeating and obesity are elevated in children of parents who have undergone weight loss surgery. Parents who have undergone weight loss surgery often report their personal history of obesity interferes with their knowledge, skills, and self-efficacy in developing their children's healthy habits, thus reducing the likelihood of addressing obesogenic environmental factors.

OBJECTIVES: This study examines whether a 6-session parent-based prevention after bariatric surgery online intervention is feasible and acceptable for parents. The study also explores the program's signal of efficacy in improving short-term outcomes related to decreased long-term risks for obesity by examining short-term impact on targeted parental cognitions, feeding practices, and child eating behaviors and physical activity habits.

SETTING: University Hospital, United States.

METHODS: Parents were recruited using flyers, clinician referrals, and social media. Measures assessed parental feeding practices, children's eating behaviors, daily hours of screen time, and outdoor play.

RESULTS: Ten families enrolled and 7 completed the study. Parents found the intervention relevant and suitable for addressing their parenting concerns. Parental feeding behaviors, such as restriction and pressure to eat, reduced while tracking of sweets and high-fat snacks increased. Children reduced both emotional overeating and undereating. Children's daily hours of screen time reduced as well as their outdoor play time.

CONCLUSIONS: Parent-based prevention after bariatric surgery aimed at helping parents who have undergone weight loss surgery engineer healthier family lifestyles is feasible, acceptable, and associated with reduced obesogenic risk factors.}, } @article {pmid32633573, year = {2021}, author = {Xu, Z and Zheng, JC and Sun, B and Zhang, K and Wang, YH and Shi, CG and Wu, HQ and Wu, XD and Chen, HJ and Yuan, W}, title = {Bi-needle technique versus transforaminal endoscopic spine system technique for percutaneous endoscopic lumbar discectomy in treating intervertebral disc calcification: a propensity score matched cohort analysis.}, journal = {British journal of neurosurgery}, volume = {35}, number = {3}, pages = {245-250}, doi = {10.1080/02688697.2020.1784393}, pmid = {32633573}, issn = {1360-046X}, mesh = {Cohort Studies ; Diskectomy ; *Diskectomy, Percutaneous ; Endoscopy ; Humans ; *Intervertebral Disc ; *Intervertebral Disc Displacement/surgery ; Lumbar Vertebrae/surgery ; Propensity Score ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the clinical results of a Bi-needle technique and conventional transforaminal endoscopic spine system (TESSYS) technique for percutaneous endoscopic lumbar discectomy (PELD) in treating patients with intervertebral disc calcification (IDC).

BACKGROUND: PELD has gained acceptance for treating patients with IDC. The Bi-needle technique was designed to improve the efficiency and safety of PELD.

METHOD: Bi-needle and TESSYS group within each cohort were balanced using 1:1 propensity score matching. Finally, 32 patients with IDC treated by Bi-needle technique from December 2015 to September 2017 were enrolled and 25 patients treated by TESSYS technique from the same spine surgery center between January 2013 and October 2017 were enrolled as controls.

RESULTS: Propensity score matching generated 22 Bi-needle and 22 TESSYS patients. There were no significant differences in visual analog scale and lumbar Japanese Orthopaedic Association scores between Bi-needle and TESSYS group. Operative time and rate of complications in the Bi-needle was significantly better than the TESSYS group (p < 0.01).

CONCLUSIONS: Both surgical methods achieved good clinical outcomes. However, compared with the TESSSY technique, operative time of the Bi-needle technique is shorter, and rate of complications is lower.}, } @article {pmid32622359, year = {2020}, author = {Pantanowitz, L and Hartman, D and Qi, Y and Cho, EY and Suh, B and Paeng, K and Dhir, R and Michelow, P and Hazelhurst, S and Song, SY and Cho, SY}, title = {Accuracy and efficiency of an artificial intelligence tool when counting breast mitoses.}, journal = {Diagnostic pathology}, volume = {15}, number = {1}, pages = {80}, pmid = {32622359}, issn = {1746-1596}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Deep Learning ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; *Mitotic Index ; }, abstract = {BACKGROUND: The mitotic count in breast carcinoma is an important prognostic marker. Unfortunately substantial inter- and intra-laboratory variation exists when pathologists manually count mitotic figures. Artificial intelligence (AI) coupled with whole slide imaging offers a potential solution to this problem. The aim of this study was to accordingly critique an AI tool developed to quantify mitotic figures in whole slide images of invasive breast ductal carcinoma.

METHODS: A representative H&E slide from 320 breast invasive ductal carcinoma cases was scanned at 40x magnification. Ten expert pathologists from two academic medical centers labeled mitotic figures in whole slide images to train and validate an AI algorithm to detect and count mitoses. Thereafter, 24 readers of varying expertise were asked to count mitotic figures with and without AI support in 140 high-power fields derived from a separate dataset. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed.

RESULTS: For each experience level the accuracy, precision and sensitivity of counting mitoses by users improved with AI support. There were 21 readers (87.5%) that identified more mitoses using AI support and 13 reviewers (54.2%) that decreased the quantity of falsely flagged mitoses with AI. More time was spent on this task for most participants when not provided with AI support. AI assistance resulted in an overall time savings of 27.8%.

CONCLUSIONS: This study demonstrates that pathology end-users were more accurate and efficient at quantifying mitotic figures in digital images of invasive breast carcinoma with the aid of AI. Higher inter-pathologist agreement with AI assistance suggests that such algorithms can also help standardize practice. Not surprisingly, there is much enthusiasm in pathology regarding the prospect of using AI in routine practice to perform mundane tasks such as counting mitoses.}, } @article {pmid32619221, year = {2020}, author = {Escoter-Torres, L and Greulich, F and Quagliarini, F and Wierer, M and Uhlenhaut, NH}, title = {Anti-inflammatory functions of the glucocorticoid receptor require DNA binding.}, journal = {Nucleic acids research}, volume = {48}, number = {15}, pages = {8393-8407}, pmid = {32619221}, issn = {1362-4962}, mesh = {Animals ; DNA/*genetics/metabolism ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation/genetics ; Glucocorticoids/genetics/metabolism ; Humans ; Inflammation/*genetics/pathology ; Mice ; Protein Interaction Domains and Motifs/genetics ; RNA-Seq ; Receptors, Glucocorticoid/*genetics ; Transcriptional Activation/genetics ; }, abstract = {The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR's anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR's zinc finger, that still tether via protein-protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.}, } @article {pmid32618495, year = {2020}, author = {Spreafico, FS and Cardoso-Filho, C and Cabello, C and Sarian, LO and Zeferino, LC and Vale, DB}, title = {Breast Cancer in Men: Clinical and Pathological Analysis of 817 Cases.}, journal = {American journal of men's health}, volume = {14}, number = {4}, pages = {1557988320908109}, pmid = {32618495}, issn = {1557-9891}, mesh = {Adult ; Age Distribution ; Aged ; Brazil ; Breast Neoplasms, Male/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/*epidemiology/*pathology ; Cross-Sectional Studies ; Early Detection of Cancer/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Sex Distribution ; }, abstract = {The objective of the current study was to describe breast cancer cases in men according to age, stage, and histology, calculating risks compared to women. It is a retrospective cross-sectional study of all breast cancer cases of the Hospital Cancer Registry of São Paulo state, Brazil, 2000-2015. Variables were age, sex, stage, and histology. Absolute numbers and proportions, Mann-Whitney test and prevalence ratio with 95% confidence interval were used. The study included 93,737 cases, of which 817 were males. The mean age at diagnosis was 60.3 years in men and 56.2 years in women (p < .001). Stage II was the most common in both sexes (33.9% in men and 36.5% in women). Men had a higher frequency of stage III than women (PR 1.18, 95% CI 1.01-1.37). Stage 0 was significantly more common in women (PR 0.69, 95% CI 0.51-0.94). Ductal carcinoma and its variants were the most common histological types in both sexes (88.7% in men and 89.0% in women). Men had a higher frequency of rarer histological types such as papillary (PR 2.17, 95% CI 1.36-3.44) and sarcomas (PR 4.10, 95% CI 1.86-9.01). In conclusion, in men, breast cancer diagnosis occurred in more advanced ages and stages. Invasive ductal carcinoma was the primary histological type observed, although rarer types were more frequent.}, } @article {pmid32618211, year = {2020}, author = {Bhattad, PB and Jain, V}, title = {Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620938942}, pmid = {32618211}, issn = {2324-7096}, mesh = {Biopsy ; Breast Neoplasms/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung/*pathology ; Lymph Nodes/*pathology ; Lymphoma/*pathology ; Magnetic Resonance Imaging ; Mediastinum/*pathology ; Middle Aged ; Neoplasm Metastasis/diagnosis ; Positron Emission Tomography Computed Tomography ; Sarcoidosis/complications/*diagnosis ; }, abstract = {Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.}, } @article {pmid32617838, year = {2021}, author = {Hashinokuchi, A and Akamine, T and Kometani, T and Shikada, Y and Nozoe, T and Kato, S}, title = {Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.}, journal = {General thoracic and cardiovascular surgery}, volume = {69}, number = {1}, pages = {137-141}, pmid = {32617838}, issn = {1863-6713}, mesh = {Aged ; *Breast Neoplasms ; Female ; Humans ; Neoplasm Recurrence, Local ; Pleurodesis ; *Pneumothorax/etiology/therapy ; Quality of Life ; Recurrence ; Thoracic Surgery, Video-Assisted ; }, abstract = {We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.}, } @article {pmid32613363, year = {2021}, author = {Sun, J and Mathias, BJ and Sun, W and Fulp, WJ and Zhou, JM and Laronga, C and Loftus, LS and Lee, MC}, title = {Is it Wise to Omit Sentinel Node Biopsy in Elderly Patients with Breast Cancer?.}, journal = {Annals of surgical oncology}, volume = {28}, number = {1}, pages = {320-329}, pmid = {32613363}, issn = {1534-4681}, mesh = {Aged ; Aged, 80 and over ; Axilla ; *Breast Neoplasms/drug therapy/surgery ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Recurrence, Local/drug therapy/surgery ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: The Society of Surgical Oncology's Choosing Wisely[®] guidelines recommend against routine sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0), hormone receptor (HR)-positive breast cancer patients aged ≥ 70 years. We examined the effect of SLNB on treatment and outcomes in this population.

MATERIALS AND METHODS: A single-institution retrospective review of consecutive cN0 women ≥ 70 years of age who received SLNB was performed. We collected clinicopathologic characteristics and treatment data. Patients were compared according to SLN status with subset analysis of HR-positive patients. Outcomes were analyzed using the Kaplan-Meier method and univariable analysis, and were compared using log-rank tests.

RESULTS: Of 500 patients, 345 (69%) were SLN-negative. Median age was 74 years (range 70-96). Most tumors were T1 (72%), N0 (69%), invasive ductal (77%), without lymphovascular invasion (88%), estrogen receptor-positive (88%) and progesterone receptor-positive (75%), and human epidermal growth factor receptor 2 (HER2)-negative (88%) treated with lumpectomy (71%). Median number of SLNs obtained was 2 (range 0-12) and median number of positive SLNs was 0 (range 0-8). Characteristics of the HR-positive subset were similar. In both the overall cohort and the HR-positive subset, SLN status significantly affected the use of adjuvant chemotherapy, although no significant effect on recurrence was observed. SLN-negative patients had better overall survival and less distant recurrence (both p < 0.0001). Adjuvant hormone therapy significantly improved overall survival.

CONCLUSIONS: SLNB can be safely omitted in elderly patients with T1, HR-positive, invasive ductal carcinoma tumors, but may still provide important information affecting treatment. Patients who are candidates for adjuvant systemic chemotherapy should still be considered for SLNB.}, } @article {pmid32612756, year = {2020}, author = {Höllbacher, B and Balázs, K and Heinig, M and Uhlenhaut, NH}, title = {Seq-ing answers: Current data integration approaches to uncover mechanisms of transcriptional regulation.}, journal = {Computational and structural biotechnology journal}, volume = {18}, number = {}, pages = {1330-1341}, pmid = {32612756}, issn = {2001-0370}, abstract = {Advancements in the field of next generation sequencing lead to the generation of ever-more data, with the challenge often being how to combine and reconcile results from different OMICs studies such as genome, epigenome and transcriptome. Here we provide an overview of the standard processing pipelines for ChIP-seq and RNA-seq as well as common downstream analyses. We describe popular multi-omics data integration approaches used to identify target genes and co-factors, and we discuss how machine learning techniques may predict transcriptional regulators and gene expression.}, } @article {pmid32609939, year = {2020}, author = {Dyer, SM and Standfield, LB and Fairhall, N and Cameron, ID and Gresham, M and Brodaty, H and Crotty, M}, title = {Supporting community-dwelling older people with cognitive impairment to stay at home: A modelled cost analysis.}, journal = {Australasian journal on ageing}, volume = {39}, number = {4}, pages = {e506-e514}, pmid = {32609939}, issn = {1741-6612}, support = {GNT9100000//National Health and Medical Research Council (NHMRC) Partnership Centre on Dealing with Cognitive and Related Functional Decline in Older People/ ; }, mesh = {Aged ; Australia ; Caregivers ; *Cognitive Dysfunction/diagnosis/therapy ; *Dementia/diagnosis/therapy ; Humans ; Independent Living ; }, abstract = {OBJECTIVE: To model the potential financial implications of Australian programs supporting cognitively impaired community-dwelling older people.

METHODS: Markov cohort models of (a) an observational study of a residential dyadic training program for carers and people with dementia (GTSAH) and (b) a frailty intervention (FIT) in a cognitively impaired subgroup. Direct health and social welfare costs accrued over 5 years (2018 $AUD prices) were captured. GTSAH costs $3755, FIT costs $1834, and permanent residential aged care (P-RAC) costs $237 per day.

RESULTS: Modelling predicted costs break even in approximately 5 months for GTSAH and 7 months for FIT, after which these interventions saved funds. The primary driver of savings was the P-RAC cost (discounted at 5%/annum), at $121 030 for GTSAH vs $231 193 for standard care; and $47 857 with FIT vs $111 359 for standard care.

CONCLUSIONS: Programs supporting cognitively impaired community-dwelling older people could be financially beneficial; further evaluation and implementation would be a worthwhile investment.}, } @article {pmid32609836, year = {2020}, author = {Sreekumar, S and Levine, KM and Sikora, MJ and Chen, J and Tasdemir, N and Carter, D and Dabbs, DJ and Meier, C and Basudan, A and Boone, D and McAuliffe, PF and Jankowitz, RC and Lee, AV and Atkinson, JM and Oesterreich, S}, title = {Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.}, journal = {Endocrinology}, volume = {161}, number = {9}, pages = {}, pmid = {32609836}, issn = {1945-7170}, support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA237736/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Line, Tumor ; Estradiol/pharmacology ; Estrogen Receptor alpha/*genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Invasiveness ; Protein Processing, Post-Translational/drug effects ; Proteolysis/drug effects ; Ubiquitination/drug effects ; }, abstract = {Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.}, } @article {pmid32607754, year = {2020}, author = {Frenkel, TI and Donzella, B and Frenn, KA and Rousseau, S and Fox, NA and Gunnar, MR}, title = {Moderating the Risk for Attention Deficits in Children with Pre-Adoptive Adversity: The Protective Role of Shorter Duration of out of Home Placement and Children's Enhanced Error Monitoring.}, journal = {Journal of abnormal child psychology}, volume = {48}, number = {9}, pages = {1115-1128}, pmid = {32607754}, issn = {1573-2835}, support = {P50 MH078105/MH/NIMH NIH HHS/United States ; R01 MH080905/MH/NIMH NIH HHS/United States ; }, mesh = {Adoption/*psychology ; Attention Deficit Disorder with Hyperactivity/*physiopathology/*psychology ; Brain/physiopathology ; Child, Foster/*psychology/statistics & numerical data ; Child, Institutionalized/*psychology/statistics & numerical data ; Child, Preschool ; Cognition/*physiology ; Electroencephalography/methods ; Evoked Potentials/physiology ; Executive Function ; Female ; Humans ; Infant ; Longitudinal Studies ; Male ; Psychiatric Status Rating Scales/statistics & numerical data ; Risk ; Time ; }, abstract = {Early institutional-deprivation has been found to increase risk for inattention/hyperactivity (ADHD). Notably, studies suggest that children with a history of adversity evidencing an enhanced ERP (the error-related-negativity; ERN) may be protected against attention problems. However, such protective effects of the ERN have been studied in children whom typically experienced residential instability. It is unknown whether error-monitoring is similarly protective for children with stable post-deprivation placements. The present study examined the protective effect of the ERN in a sample of children who experienced at least 3-years of stable, relatively enriched caregiving after being internationally-adopted as infants/toddlers from institutional-care. We included two groups of children adopted internationally before age three, one group adopted from institutional-care (PI:n = 80) and one comparison group adopted from foster-care (FC;n = 44). A second comparison group consisted of non-adopted children (NA;n = 48) from demographically comparable families. At five-years of age, we assessed child ADHD symptoms (parent-report) and behavioral performance and neural correlates of error-monitoring (Go/No-Go task). PI children displayed lower Go/No-Go accuracy relative to FC children, and higher levels of ADHD symptoms relative to NA controls. In both FC and PI groups, longer duration of pre-adoptive out-of-home placement was associated with inattention, especially for children with deficits in error-monitoring. Enhancing cognitive control in the form of error monitoring might be a useful intervention target to protect children from some of the negative outcomes associated with adverse early care. Furthermore, results underscore that regardless of type of pre-adoptive care, we should aim to place children in stable/permanent homes as early as possible.}, } @article {pmid32606498, year = {2020}, author = {Das, DK and Pathan, SK and Sheikh, ZA and Mallik, MK and John, B and Mothaffer, F}, title = {Fine-Needle Cytological Characteristics of Carcinoma Breast with Medullary or Medullary-like Features Masquerading as Dendritic Reticulum Cell Sarcoma: An Attempt to Explore the Reasons for Erroneous Cytologic Interpretation.}, journal = {Journal of cytology}, volume = {37}, number = {2}, pages = {99-107}, pmid = {32606498}, issn = {0970-9371}, abstract = {BACKGROUND: Infiltration of tumors by dendritic reticulum cells (DRC) reflects the host immune defense mechanism. We observed three breast carcinomas cases with dense tumor-infiltrating DRC and lymphocytes in fine-needle aspiration (FNA) smears, leading to cytodiagnosis or differential diagnosis of dendritic reticulum cell sarcoma (DRCS). An attempt was made to find out the reason behind such an erroneous interpretation.

MATERIALS AND METHODS: Between 2009 and 2014, two cases were diagnosed as DRCS of the female breast by FNA cytology and in one case possibility of DRCS was considered along with medullary breast carcinoma (MBC). We compare and contrast the cytomorphological features of these three cases with those of nine cytologically diagnosed MBC.

RESULTS: Cases diagnosed as DRCS or MBC showed singly dispersed tumor cells, nuclear pleomorphism, bare nuclei, prominent nucleoli, and presence of lymphocytes. There was no significant difference between the two groups for discohesive clusters, syncytial clusters, plasma cells, neutrophils, foamy histiocytes, and necrosis. However, there was significant difference for presence of cohesive clusters (0% DRCS and 100% MBC, P = 0.00485), severe degree (+++) of pleomorphism (100% DRCS vs. 11.1% MBC, P = 0.01818), +++ DRC (P = 0.04697), and DRC with ++ to +++ enlarged nuclei (P = 0.03333), and pleomorphic nuclei (P = 0.00833). Two of the three cytologically diagnosed DRCS cases proved to be MBC or MBC-like and one as invasive ductal carcinoma. Six of nine cytologically diagnosed MBC cases with histology proved to be invasive breast carcinomas.

CONCLUSION: Criteria for cytodiagnosis MBC need a fresh look. Cases with numerous dendritic cells possibly represent MBC.}, } @article {pmid32601553, year = {2020}, author = {George, J and Albach, A and Robinson, AS and Dixon, L and Nguyen, QD}, title = {Diagnosis, Prognosis, and Management of Breast Cancer in an 81-Year-Old Male Patient.}, journal = {Cureus}, volume = {12}, number = {5}, pages = {e8277}, pmid = {32601553}, issn = {2168-8184}, abstract = {Due to the lower rate of breast cancer in men compared to women, there are fewer studies on which to base the treatment of a male patient with breast cancer; and this is further complicated when the patient is part of the elderly population. We report the case of an 81-year-old male who came in for imaging of pulmonary nodules and had an incidental finding of abnormal growth in the breast. Further imaging was performed, and biopsy was completed, confirming invasive ductal carcinoma. Eventually, the patient was treated with a modified radical mastectomy. In this report, we also engage in a discussion of the treatment considerations for patients of male sex and older age group.}, } @article {pmid32599083, year = {2020}, author = {Grabenstetter, A and Mohanty, AS and Rana, S and Zehir, A and Brannon, AR and D'Alfonso, TM and DeLair, DF and Tan, LK and Ross, DS}, title = {E-cadherin immunohistochemical expression in invasive lobular carcinoma of the breast: correlation with morphology and CDH1 somatic alterations.}, journal = {Human pathology}, volume = {102}, number = {}, pages = {44-53}, pmid = {32599083}, issn = {1532-8392}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD/biosynthesis/*genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cadherins/biosynthesis/*genetics ; Carcinoma, Lobular/diagnosis/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Mutation ; }, abstract = {E-cadherin (ECAD) immunohistochemical (IHC) expression is lost in ∼90% of invasive lobular carcinomas (ILCs) owing to genomic alterations of CDH1. We examined morphologic features and ECAD IHC expression in invasive breast carcinomas (BCs) with known CDH1 alterations. Between January 2014 and May 2018, 202 cases of BC with a CDH1 somatic alteration were identified. ECAD expression was lost in 77% (155/202) of cases and was retained in 23% (47/202) cases. Most (90%, 139/155) ECAD-negative cases were morphologically classified as ILC, while the remaining (10%, 16/155) were invasive mammary carcinoma with mixed ductal and lobular features (IMC). Of 47 cases with ECAD staining, 62% (29/47) were classified as ILC, 23% (11/47) were classified as IMC, and 15% (7/47) were classified as invasive ductal carcinoma (IDC). Of note, 51% (24/47) of ECAD-positive cases were initially diagnosed as IDC or IMC based on ECAD expression alone. For ECAD-negative BCs, 98% (152/155) of CDH1 alterations were truncating, and 2% (3/155) were variants of unknown significance (VUS). Truncating CDH1 alterations were identified in the majority of ECAD-positive BCs (72%, 34/47); however, VUS-type CDH1 alterations were more prevalent (28%, 13/47) in ECAD-positive BCs than in ECAD-negative BCs. Although 90% of ECAD-negative tumors were compatible with ILC in this study, 17% (29/168) of ILC cases were ECAD positive. In addition, CDH1 truncating alterations were seen in ECAD-positive ILC, supporting the notion of aberrant ECAD staining. Therefore, ECAD IHC expression must be interpreted in conjunction with morphology, and BC with classic histologic features of ILC should not be reclassified as IDC/IMC based solely on the status of ECAD IHC expression.}, } @article {pmid32597374, year = {2021}, author = {Gazit, T and Amichai-Hamburger, Y}, title = {Factors Underlying Engagement in Facebook Support Groups of Female Infertility Patients.}, journal = {Psychological reports}, volume = {124}, number = {3}, pages = {1150-1173}, doi = {10.1177/0033294120934703}, pmid = {32597374}, issn = {1558-691X}, mesh = {Adult ; Child ; Female ; Humans ; Infertility, Female/*psychology/*therapy ; *Self-Help Groups ; *Social Media ; *Social Participation ; *Social Support ; Surveys and Questionnaires ; }, abstract = {Women dealing with infertility issues may well undergo a long process of treatments and they are also likely to feel empty, defective, inadequate and worthless. Some of these women join online support groups in order to share their experiences, get information and ease their pain. One important positive phenomenon of the Internet is the advent of online support groups. These are designed to foster well-being and increased social interaction, and to offer 24/7 availability with no geographical restrictions. This study, comprising 191 female participants who answered an online survey, focused on closed Facebook support groups, the members of which were women undergoing treatments for infertility. The study examined to what extent the degree of engagement by these women in online support groups could be predicted by external factors (family status, social and family support, the importance of the group and the duration of membership) and internal factors (extroversion, openness to experience, subjective happiness and loneliness). Findings show that higher levels of engagement in such Facebook support groups are predicted by the external factors, including having a child, longer duration of membership in the group, family support and the strongest predictor, perception of the group as important. Findings also show that higher levels of engagement in these groups are predicted by internal factors extroversion and openness to experience, as was found in previous studies of other populations. Results and future research are discussed.}, } @article {pmid32596132, year = {2020}, author = {Mitaka, H and Jammal, R and Saabiye, J and Yancovitz, S and Perlman, DC}, title = {Giant cellulitis-like Sweet syndrome: An underrecognized clinical variant mimicking skin and soft tissue infection.}, journal = {IDCases}, volume = {21}, number = {}, pages = {e00874}, pmid = {32596132}, issn = {2214-2509}, abstract = {A new clinical variant of Sweet syndrome, called giant cellulitis-like Sweet syndrome, can masquerade as cellulitis because the patients present with an acute onset of large erythematous plaques, fever, and leukocytosis with neutrophil predominance. This case describes a 90-year-old female with a history of invasive ductal carcinoma of the breast who presented with 3 days of erythema of the right chest and right leg. Physical examination was notable for well-demarcated, blanching erythematous rashes involving the right chest and right lower extremity. Laboratory data was notable for neutrophilic leukocytosis. A clinical diagnosis of cellulitis was made initially, and intravenous cefazolin was initiated. The rash had only partially improved with antibiotics. Skin biopsy revealed a dense neutrophilic infiltrate, which was consistent with Sweet syndrome. Based on the widespread plaques, this case was considered a "giant cellulitis-like" variant of Sweet syndrome. Clinicians should have a high index of suspicion for Sweet syndrome when assessing a patient with fever, neutrophilia and erythematous skin plaques atypical of cellulitis because this condition does not respond to antimicrobial therapy and requires systemic glucocorticoid therapy.}, } @article {pmid32595663, year = {2020}, author = {Lurthy, T and Cantat, C and Jeudy, C and Declerck, P and Gallardo, K and Barraud, C and Leroy, F and Ourry, A and Lemanceau, P and Salon, C and Mazurier, S}, title = {Impact of Bacterial Siderophores on Iron Status and Ionome in Pea.}, journal = {Frontiers in plant science}, volume = {11}, number = {}, pages = {730}, pmid = {32595663}, issn = {1664-462X}, abstract = {Including more grain legumes in cropping systems is important for the development of agroecological practices and the diversification of protein sources for human and animal consumption. Grain legume yield and quality is impacted by abiotic stresses resulting from fluctuating availabilities in essential nutrients such as iron deficiency chlorosis (IDC). Promoting plant iron nutrition could mitigate IDC that currently impedes legume cultivation in calcareous soils, and increase the iron content of legume seeds and its bioavailability. There is growing evidence that plant microbiota contribute to plant iron nutrition and might account for variations in the sensitivity of pea cultivars to iron deficiency and in fine to seed nutritional quality. Pyoverdine (pvd) siderophores synthesized by pseudomonads have been shown to promote iron nutrition in various plant species (Arabidopsis, clover and grasses). This study aimed to investigate the impact of three distinct ferripyoverdines (Fe-pvds) on iron status and the ionome of two pea cultivars (cv.) differing in their tolerance to IDC, (cv. S) being susceptible and (cv. T) tolerant. One pvd came from a pseudomonad strain isolated from the rhizosphere of cv. T (pvd1T), one from cv. S (pvd2S), and the third from a reference strain C7R12 (pvdC7R12). The results indicated that Fe-pvds differently impacted pea iron status and ionome, and that this impact varied both according to the pvd and the cultivar. Plant iron concentration was more increased by Fe-pvds in cv. T than in cv. S. Iron allocation within the plant was impacted by Fe-pvds in cv. T. Furthermore, Fe-pvds had the greatest favorable impact on iron nutrition in the cultivar from which the producing strain originated. This study evidences the impact of bacterial siderophores on pea iron status and pea ionome composition, and shows that this impact varies with the siderophore and host-plant cultivar, thereby emphasizing the specificity of these plant-microorganisms interactions. Our results support the possible contribution of pyoverdine-producing pseudomonads to differences in tolerance to IDC between pea cultivars. Indeed, the tolerant cv. T, as compared to the susceptible cv. S, benefited from bacterial siderophores for its iron nutrition to a greater extent.}, } @article {pmid32592357, year = {2020}, author = {Shojaee, L and Abedinnegad, S and Nafisi, N and Naghshvar, F and Godazandeh, G and Moradi, S and Shakeri Astani, K and Godazandeh, Y}, title = {Sentinel Node Biopsy in Early Breast Cancer Patients with Palpable Axillary Node.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {6}, pages = {1631-1636}, pmid = {32592357}, issn = {2476-762X}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision/*methods ; Lymph Nodes/metabolism/*pathology/surgery ; Mastectomy ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Sentinel Lymph Node Biopsy/*methods ; }, abstract = {BACKGROUND: Sentinel lymph node biopsy is a reliable method for evaluation of the axillary lymph node status in early stage breast cancer patients with non-palpable lymph nodes. The present study evaluated the status of sentinel and non-sentinel lymph nodes in T1T2 patients with palpable axillary lymph nodes.

MATERIALS AND METHODS: One hundred and two women with early breast cancer were investigated in this study. Patients were selected for axillary sentinel lymph node biopsy and then surgery .Then the rates of false negative and true positive, and diagnostic accuracy of sentinel lymph nodes biopsy were evaluated. In addition, the hormone receptors status of the tumor was determined through IHC and data was analyzed in SPSS21.

RESULTS: In this study, the mean age of the patients was 49 years, 85% had invasive ductal carcinoma  in their pathology reports, 77% were ER/PR positive, 30% HER2 positive and 9.8% triple negative and 69% had KI67<14%. In frozen pathology, 15.7 and 84.3% were sentinel positive and negative, respectively, and in the final pathology, 41 and 58.8% were sentinel positive and negative, respectively. This difference arises from the false negative rate of the frozen pathology, which was about 31.3%. The sensitivity, specificity, and diagnostic accuracy of the frozen section were 24, 90 and 43%, respectively. Lymphovascular invasion is an important effective factor in the involvement of sentinel and non-sentinel lymph nodes. Statistical analysis showed that the probability of sentinel and non-sentinel lymph nodes involvement was higher in receptor positive patients and those with KI67>14% (p<0.002) whereas the rate of involvement was lower in triple negative patients.

CONCLUSION: Sentinel node biopsy can be used in a significant percentage of breast cancer patients with palpable and reactive axillary lymph nodes.}, } @article {pmid32590741, year = {2020}, author = {Zheng, L and Zhao, Y and Liu, F and Liu, P and Li, W and Yang, Y and Zhang, H and Liu, Y}, title = {Prognostic significance of preoperative albumin to fibrinogen ratio associated nomograms in patients with breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {99}, number = {26}, pages = {e20681}, pmid = {32590741}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood/*mortality/surgery ; Carcinoma, Ductal, Breast/blood/*mortality/surgery ; Disease-Free Survival ; Female ; Fibrinogen/*analysis ; Humans ; Middle Aged ; *Nomograms ; Preoperative Period ; Prognosis ; Retrospective Studies ; *Serum Albumin ; }, abstract = {Plasma albumin to fibrinogen ratio is involved in human cancer, but its prognostic significance in breast cancer is controversy. In the context of breast invasive ductal carcinoma, this research aims to retrospectively evaluate by preoperative plasma albumin to fibrinogen ratio (AFR) and forecast oncological outcome and recurrence.This retrospective study comprised 230 patients with non-metastatic breast invasive ductal carcinoma who underwent surgery between January 2009 and April 2012 in Fourth Hospital of Hebei Medical University. Patients were categorized base on an optimal value of preoperative plasma fibrinogen (Fib) and albumin. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between albumin to fibrinogen ratio and clinical outcomes were assessed with univariate and multivariate analysis. A number of risk factors were used to form nomograms to evaluate survival, and Harrell concordance index (C-index) was used to evaluate the predictive accuracy.Plasma AFR was significantly associated with diminished disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that plasma AFR was an independent prognostic indicator for DFS (HR = 1.346; 95% CI: 1.107-1.636; P = .03) and overall survival (OS) (HR = 1.485; 95% CI: 1.106-1.993; P = .008). Two prediction model of 3-, 5-years OS and DFS based on the AFR was developed.Elevated preoperative plasma AFR is an independent prognostic factor for oncological outcomes in patients with breast invasive ductal carcinoma. The formulated nomogram showed superior predictive accuracy for DFS and OS.}, } @article {pmid32589068, year = {2021}, author = {Epstein, JI and Amin, MB and Fine, SW and Algaba, F and Aron, M and Baydar, DE and Beltran, AL and Brimo, F and Cheville, JC and Colecchia, M and Comperat, E and da Cunha, IW and Delprado, W and DeMarzo, AM and Giannico, GA and Gordetsky, JB and Guo, CC and Hansel, DE and Hirsch, MS and Huang, J and Humphrey, PA and Jimenez, RE and Khani, F and Kong, Q and Kryvenko, ON and Kunju, LP and Lal, P and Latour, M and Lotan, T and Maclean, F and Magi-Galluzzi, C and Mehra, R and Menon, S and Miyamoto, H and Montironi, R and Netto, GJ and Nguyen, JK and Osunkoya, AO and Parwani, A and Robinson, BD and Rubin, MA and Shah, RB and So, JS and Takahashi, H and Tavora, F and Tretiakova, MS and True, L and Wobker, SE and Yang, XJ and Zhou, M and Zynger, DL and Trpkov, K}, title = {The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.}, journal = {Archives of pathology & laboratory medicine}, volume = {145}, number = {4}, pages = {461-493}, doi = {10.5858/arpa.2020-0015-RA}, pmid = {32589068}, issn = {1543-2165}, mesh = {Biomarkers, Tumor/analysis/genetics ; Biopsy, Needle/standards ; Consensus ; Humans ; Image-Guided Biopsy/standards ; Immunohistochemistry/standards ; Magnetic Resonance Imaging/standards ; Male ; Molecular Diagnostic Techniques/standards ; Neoplasm Grading/*standards ; Pathology/*standards ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/genetics/*pathology ; }, abstract = {CONTEXT.—: Controversies and uncertainty persist in prostate cancer grading.

OBJECTIVE.—: To update grading recommendations.

DATA SOURCES.—: Critical review of the literature along with pathology and clinician surveys.

CONCLUSIONS.—: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.}, } @article {pmid32586354, year = {2020}, author = {Blohmer, M and Zhu, L and Atkinson, JM and Beriwal, S and Rodríguez-López, JL and Rosenzweig, M and Brufsky, AM and Tseng, G and Lucas, PC and Lee, AV and Oesterreich, S and Jankowitz, RC}, title = {Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {70}, pmid = {32586354}, issn = {1465-542X}, support = {SAC160073/KOMEN/Susan G. Komen/United States ; CCR14300865/KOMEN/Susan G. Komen/United States ; SAC150021/KOMEN/Susan G. Komen/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; U24 CA180921/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/metabolism/pathology/radiotherapy ; Carcinoma, Lobular/metabolism/*mortality/pathology/radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Orbital Neoplasms/metabolism/radiotherapy/*secondary ; Prognosis ; Radiotherapy, Intensity-Modulated ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.

METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.

RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.

CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.}, } @article {pmid32585859, year = {2020}, author = {Carrasco-Zafra, MI and Gómez-García, R and Ocaña-Riola, R and Martín-Roselló, ML and Blanco-Reina, E}, title = {Level of Palliative Care Complexity in Advanced Cancer Patients: A Multinomial Logistic Analysis.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32585859}, issn = {2077-0383}, abstract = {The current treatment approach for patients in palliative care (PC) requires a health model based on shared and individualised care, according to the degree of complexity encountered. The aims of this study were to describe the levels of complexity that may be present, to determine their most prevalent elements and to identify factors that may be related to palliative complexity in advanced-stage cancer patients. An observational retrospective study was performed of patients attended to at the Cudeca Hospice. Socio-demographic and clinical data were compiled, together with information on the patients' functional and performance status (according to the Palliative Performance Scale (PPS)). The level of complexity was determined by the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal©) and classified as highly complex, complex or non-complex. The impact of the independent variables on PC complexity was assessed by multinomial logistic regression analysis. Of the 501 patients studied, 44.8% presented a situation classed as highly complex and another 44% were considered complex. The highly complex items most frequently observed were the absence or insufficiency of family support and/or caregivers (24.3%) and the presence of difficult-to-control symptoms (17.3%). The complex item most frequently observed was an abrupt change in the level of functional autonomy (47.6%). The main factor related to the presence of high vs. non-complexity was that of performance status (odds ratio (OR) = 10.68, 95% confidence interval (CI) = 2.81-40.52, for PPS values < 40%). However, age was inversely related to high complexity. This study confirms the high level of complexity present in patients referred to a PC centre. Determining the factors related to this complexity could help physicians identify situations calling for timely referral for specialised PC, such as a low PPS score.}, } @article {pmid32585364, year = {2020}, author = {Erener, S}, title = {Diabetes, infection risk and COVID-19.}, journal = {Molecular metabolism}, volume = {39}, number = {}, pages = {101044}, pmid = {32585364}, issn = {2212-8778}, mesh = {Adult ; Aged ; Animals ; *Betacoronavirus ; COVID-19 ; Child ; Comorbidity ; Coronavirus Infections/*epidemiology/immunology/pathology/virology ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/*epidemiology/immunology ; Diabetes Mellitus, Type 2/*epidemiology/immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Incidence ; Male ; Mice ; Middle Aged ; Pandemics ; Pneumonia, Viral/*epidemiology/immunology/pathology/virology ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.

SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided.

MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.}, } @article {pmid32581209, year = {2020}, author = {Lan, T and Lu, Y and Luo, H and He, J and He, J and Hu, Z and Xu, H}, title = {Effects of Marital Status on Prognosis in Women with Infiltrating Ductal Carcinoma of the Breast: A Real-World 1: 1 Propensity-Matched Study.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e923630}, pmid = {32581209}, issn = {1643-3750}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal/mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Marital Status/*statistics & numerical data ; Middle Aged ; Multivariate Analysis ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND The effects of marital status on infiltrating ductal carcinoma of breast cancer (IDC) have not been studied in detail. This study investigated the impact of marital status on IDC patients. MATERIAL AND METHODS SEER databases were searched from 2010 to 2015 for subjects who were married, divorced, single, and widowed. The influence of marital status on breast cancer-specific survival (BCSS) and overall survival (OS) of IDC patients was investigated through multivariate Cox regression analysis and Kaplan-Meier analysis. To prevent bias, propensity score matching (PSM) analysis was performed. RESULTS The 5-year OS was 89.6%in married patients, 84.9% in divorced patients, 83.5% in single patients, and 71.3% in widowed patients (p<0.001). The 5-year BCSS were 92.9%, 90.2%, 87.6%, and 86.4%, respectively (p<0.001). Multivariate Cox regression analysis revealed that marriage was a protective factor for patients with IDC in terms of OS (divorced: HR, 1.27; 95% CI, 1.21-1.32; p<0.001; single: HR, 1.36; 95% CI, 1.31-1.42; p<0.001; widowed: HR, 1.42; 95% CI, 1.36-1.48; p<0.001) and BCSS (divorced: HR, 1.15; 95% CI, 1.09-1.21; p<0.001; single: HR, 1.27; 95% CI, 1.21-1.33; p<0.001; widowed: HR, 1.32; 95% CI, 1.25-1.40; p<0.001). Following subgroup and PSM analysis, married patients were shown to have better OS and BCSS as opposed to divorced, single, or widowed patients. CONCLUSIONS We identify marital status as a predictor of survival in those with IDC. Widowed patients showed the highest mortality risk.}, } @article {pmid32580398, year = {2020}, author = {Kim, HM and Koo, JS}, title = {Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32580398}, issn = {1422-0067}, support = {2016 (6-2016-0163)//faculty research grant from Yonsei University College of Medicine/ ; }, mesh = {Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/immunology/metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/metabolism/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/*classification/*immunology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; STAT6 Transcription Factor/metabolism ; Survival Rate ; }, abstract = {The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.}, } @article {pmid32579999, year = {2020}, author = {Meijers, A and Guterres Marmitt, G and Ng Wei Siang, K and van der Schaaf, A and Knopf, AC and Langendijk, JA and Both, S}, title = {Feasibility of patient specific quality assurance for proton therapy based on independent dose calculation and predicted outcomes.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {150}, number = {}, pages = {136-141}, doi = {10.1016/j.radonc.2020.06.027}, pmid = {32579999}, issn = {1879-0887}, mesh = {Feasibility Studies ; Humans ; *Proton Therapy ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; *Radiotherapy, Intensity-Modulated ; Retrospective Studies ; }, abstract = {PURPOSE: Patient specific quality assurance (PSQA) is required to verify the treatment delivery and the dose calculation by the treatment planning system (TPS). The objective of this work is to demonstrate the feasibility to substitute resource consuming measurement based PSQA (PSQAM) by independent dose recalculations (PSQAIDC), and that PSQAIDC results may be interpreted in a clinically relevant manner using normal tissue complication probability (NTCP) and tumor control probability (TCP) models.

METHODS AND MATERIALS: A platform for the automatic execution of the two following PSQAIDC workflows was implemented: (i) using the TPS generated plan and (ii) using treatment delivery log files (log-plan). 30 head and neck cancer (HNC) patients were retrospectively investigated. PSQAM results were compared with those from the two PSQAIDC workflows. TCP/NTCP variations between PSQAIDC and the initial TPS dose distributions were investigated. Additionally, for two example patients that showed low passing PSQAM results, eight error scenarios were simulated and verified via measurements and log-plan based calculations. For all error scenarios ΔTCP/NTCP values between the nominal and the log-plan dose were assessed.

RESULTS: Results of PSQAM and PSQAIDC from both implemented workflows agree within 2.7% in terms of gamma pass ratios. The verification of simulated error scenarios shows comparable trends between PSQAM and PSQAIDC. Based on the 30 investigated HNC patients, PSQAIDC observed dose deviations translate into a minor variation in NTCP values. As expected, TCP is critically related to observed dose deviations.

CONCLUSIONS: We demonstrated a feasibility to substitute PSQAM with PSQAIDC. In addition, we showed that PSQAIDC results can be interpreted in clinically more relevant manner, for instance using TCP/NTCP.}, } @article {pmid32576277, year = {2020}, author = {Ali, ET and Masri, MAM and Siddig, EE and Ahmed, A and Muneer, MS and Mohamed, NS and Edris, AMM}, title = {Immunohistochemical expression of interleukin-17 and hormonal receptors in benign and malignant breast lesions.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {300}, pmid = {32576277}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-17/*metabolism ; Middle Aged ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {OBJECTIVES: IL17 is a critical pro-inflammatory cytokine that is involved in inflammation, multidrug resistance and growth persistence pathways in cancer. This study is aiming at studying the expression of IL17 and hormonal receptors expression in benign and malignant breast lesions using immunohistochemical staining methods.

RESULTS: A total of 137 cases of breast lesions were studied, 97 (70.8%) were malignant and 40 (29.2%) were benign cases. Age range for malignant and benign cases were between 26 and 80 years [mean age 50 ± 2 years], and 20 to 70 years [mean age 41 ± 4 years], respectively, Odds ratio = 2.3 [1.78-1.99, 95% CI]. The majority of the histopathological diagnosis of the benign and malignant lesions were 21 (15.3%) fibro-adenomas and 87 (63.5%) invasive ductal carcinoma, respectively. Expression of IL17 and age were insignificantly negatively correlated for both groups; benign cases [r = - 0.054, P value 0.742] and malignant cases [r = - 0.080, P value 0.444]. IL17 expression was showing insignificant association with age group, P value 0.065. IL17 expression showed a statistical significance based on the different histopathological diagnosis, P value 0.035. Expression levels of estrogen, progesterone, and human epidermal receptors were showing insignificant difference among IL17 expression categories, P values 0.678, 0.623, and 0.361, respectively.}, } @article {pmid32565323, year = {2020}, author = {Yoon, EC and Wilson, P and Zuo, T and Pinto, M and Cole, K and Harigopal, M}, title = {High frequency of p16 and SOX10 coexpression but not androgen receptor expression in triple-negative breast cancers.}, journal = {Human pathology}, volume = {102}, number = {}, pages = {13-22}, doi = {10.1016/j.humpath.2020.06.004}, pmid = {32565323}, issn = {1532-8392}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis ; Female ; Humans ; Keratin-5/biosynthesis ; Keratin-6/biosynthesis ; Middle Aged ; Receptors, Androgen/*biosynthesis ; SOXE Transcription Factors/*biosynthesis ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {Triple-negative breast cancers (TNBCs) represent approximately 12-17% of all breast cancers and have distinctively aggressive clinical courses. Because routine biomarkers for breast cancer do not apply for TNBCs, it is essential to find novel prognostic markers and potential targets for therapeutic agents. p16 and SOX10 are emerging biomarkers with relatively unexplored expressions in TNBCs. We present an analysis of the expression of p16 and SOX10 in combination with that of androgen receptor (AR) and cytokeratin (CK) 5/6 in TNBCs. In addition, we used tissue microarrays (TMAs) to compare frequencies of p16 and SOX10 between TNBCs and non-TNBCs. Fifty-six TNBC samples with clinical data were stained immunohistochemically with p16, SOX10, AR, and CK5/6. Fifty-four cases (96.4%) were invasive ductal carcinoma, not otherwise specified, and 46 cases (82.1%) were Nottingham histologic grade 3. The majority of TNBC cases were positive for p16 (n = 44; 78.6%) and SOX10 (n = 48; 85.7%). AR was positive in 15 cases (26.8%). CK5/6 was positive in 24 cases (42.9%), which were classified as basal-like breast cancer (BLBC) subtype. The frequencies of p16 and SOX10 expression in BLBC and non-BLBC subtypes did not reveal significant statistical difference in a separate analysis. Using archived TNBC and non-TNBC TMAs, we observed that 56% of TNBC cases were positive for p16 compared with 16% of non-TNBC cases (p-value <0.0001). SOX10 was positive in 80% of TNBC cases compared with 35% of non-TNBC cases (p-value <0.0001). A significant correlation was observed between p16 and SOX10 coexpression in TNBC cases (n = 56/80, p = 0.02) but not in non-TNBC cases (n = 23/348; p = 0.626). In conclusion, p16 and SOX10 are frequently expressed in TNBC, regardless of CK5/6 expression. Furthermore, p16 and SOX10 are often coexpressed in TNBCs compared with non-TNBCs.}, } @article {pmid32563094, year = {2020}, author = {Yoneyama, K and Nakagawa, M and Hara, A}, title = {Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {72}, number = {}, pages = {318-321}, pmid = {32563094}, issn = {2210-2612}, abstract = {INTRODUCTION: Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case.

PRESENTATION OF CASE: A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection.

DISCUSSION: Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases.

CONCLUSION: The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.}, } @article {pmid32561662, year = {2020}, author = {Sestak, I and Filipits, M and Buus, R and Rudas, M and Balic, M and Knauer, M and Kronenwett, R and Fitzal, F and Cuzick, J and Gnant, M and Greil, R and Dowsett, M and Dubsky, P}, title = {Prognostic Value of EndoPredict in Women with Hormone Receptor-Positive, HER2-Negative Invasive Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {17}, pages = {4682-4687}, doi = {10.1158/1078-0432.CCR-20-0260}, pmid = {32561662}, issn = {1557-3265}, support = {5032/CRUK_/Cancer Research UK/United Kingdom ; C569/A16891/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast/*pathology/surgery ; Breast Neoplasms/genetics/*mortality/pathology/therapy ; Carcinoma, Lobular/genetics/*mortality/pathology/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials, Phase III as Topic ; Datasets as Topic ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/genetics/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Risk Assessment/methods ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) accounts for approximately 5%-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC).

EXPERIMENTAL DESIGN: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0-10 in postmenopausal women with ILC. The primary outcome was DR.

RESULTS: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54-4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73-2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7-8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0-35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63-4.02)] and node-positive disease [HR = 3.70 (2.49-5.50)].

CONCLUSIONS: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.}, } @article {pmid32554183, year = {2020}, author = {Horowitz, I and Avirame, K and Naim-Feil, J and Rubinson, M and Moses, E and Gothelf, D and Levit-Binnun, N}, title = {The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study.}, journal = {Psychiatry research}, volume = {291}, number = {}, pages = {113056}, doi = {10.1016/j.psychres.2020.113056}, pmid = {32554183}, issn = {1872-7123}, mesh = {Adolescent ; Attention/drug effects/physiology ; Attention Deficit Disorder with Hyperactivity/*drug therapy/*psychology ; Central Nervous System Stimulants/pharmacology/*therapeutic use ; Child ; Cognition/*drug effects/physiology ; Cross-Over Studies ; Double-Blind Method ; Female ; Humans ; Male ; Methylphenidate/pharmacology/*therapeutic use ; Neuropsychological Tests ; Psychomotor Performance/*drug effects/physiology ; Reaction Time/drug effects/physiology ; Reproducibility of Results ; }, abstract = {Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.}, } @article {pmid32551954, year = {2020}, author = {Bosso, G and Valvano, A and Apuzzi, V and Mercurio, V and Di Simone, V and Cittadini, A and Napoli, R and Oliviero, U}, title = {Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.}, journal = {Angiology}, volume = {71}, number = {8}, pages = {726-733}, doi = {10.1177/0003319720932803}, pmid = {32551954}, issn = {1940-1574}, mesh = {Aged ; Brachial Artery/diagnostic imaging/*physiopathology ; Cardiomyopathy, Dilated/diagnostic imaging/*etiology/*physiopathology ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*complications/diagnosis/physiopathology ; Prognosis ; Risk Assessment ; Risk Factors ; *Vascular Stiffness ; *Vasodilation ; }, abstract = {Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.}, } @article {pmid32549116, year = {2020}, author = {Buffolo, E and Wanderley, J and Mendonça, JT and Lima, RC and Brofman, PR and Lucchese, FA and Jatene, FB}, title = {Domingo Marcolino Braile (1938-2020) Surgeon - Scientist - Professor - Businessman - Aviator The last flight of a great man.}, journal = {Brazilian journal of cardiovascular surgery}, volume = {35}, number = {3}, pages = {VII-IX}, doi = {10.21470/1678-9741-1-2020-0605}, pmid = {32549116}, issn = {1678-9741}, } @article {pmid32548206, year = {2020}, author = {Arensman, K and Dela-Pena, J and Miller, JL and LaChance, E and Beganovic, M and Anderson, M and Rivelli, A and Wieczorkiewicz, SM}, title = {Impact of Mandatory Infectious Diseases Consultation and Real-time Antimicrobial Stewardship Pharmacist Intervention on Staphylococcus aureus Bacteremia Bundle Adherence.}, journal = {Open forum infectious diseases}, volume = {7}, number = {6}, pages = {ofaa184}, pmid = {32548206}, issn = {2328-8957}, abstract = {BACKGROUND: The purpose of this study was to evaluate the impact of infectious diseases consultation (IDC) and a real-time antimicrobial stewardship (AMS) review on the management of Staphylococcus aureus bacteremia (SAB).

METHODS: This retrospective study included adult inpatients with SAB from January 2016 to December 2018 at 7 hospitals. Outcomes were compared between 3 time periods: before mandatory IDC and AMS review (period 1), after mandatory IDC and before AMS review (period 2), and after mandatory IDC and AMS review (period 3). The primary outcome was bundle adherence, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary end points included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related readmission, and in-hospital all-cause mortality.

RESULTS: A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n = 241/371), 54% in period 2 (n = 47/87), and 76% in period 3 (n = 92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.93; P = .02) and period 2 (OR, 0.37; 95% CI, 0.20-0.67; P = .0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P < .001), source control (34% vs 45% vs 45%; P = .04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P = .01). No differences were noted for readmission or mortality.

CONCLUSIONS: The addition of AMS pharmacist review to mandatory IDC was associated with significantly improved quality care bundle adherence.}, } @article {pmid32544183, year = {2020}, author = {Moon, HR and Ospina-Muñoz, N and Noe-Kim, V and Yang, Y and Elzey, BD and Konieczny, SF and Han, B}, title = {Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.}, journal = {PloS one}, volume = {15}, number = {6}, pages = {e0234012}, pmid = {32544183}, issn = {1932-6203}, support = {P30 CA023168/CA/NCI NIH HHS/United States ; UL1 TR000006/TR/NCATS NIH HHS/United States ; HHSN261201400021C/CA/NCI NIH HHS/United States ; }, mesh = {CD24 Antigen/metabolism ; Carcinoma, Ductal, Breast/classification/genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Humans ; Microfluidics/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Triple Negative Breast Neoplasms/classification/genetics/*pathology ; *Tumor Microenvironment ; }, abstract = {Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.}, } @article {pmid32542746, year = {2020}, author = {Rijstenberg, LL and Hansum, T and Hollemans, E and Kweldam, CF and Kümmerlin, IP and Bangma, CH and van der Kwast, TH and Roobol, MJ and van Leenders, GJLH}, title = {Intraductal carcinoma has a minimal impact on Grade Group assignment in prostate cancer biopsy and radical prostatectomy specimens.}, journal = {Histopathology}, volume = {77}, number = {5}, pages = {742-748}, pmid = {32542746}, issn = {1365-2559}, mesh = {Aged ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading/methods ; Prostatectomy ; Prostatic Neoplasms/*pathology ; }, abstract = {AIMS: Intraductal carcinoma (IDC) is an adverse histopathological parameter for prostate cancer outcome, but is not incorporated in current tumour grading. To account for its dismal prognosis and to omit basal cell immunohistochemistry, it has been proposed to grade IDC on the basis of its underlying architectural pattern. The aim of this study was to determine the impact of IDC grade assignment on prostate cancer biopsy and radical prostatectomy tumour grading.

METHODS AND RESULTS: A cohort of 1031 prostate cancer biopsies and 835 radical prostatectomies were assigned a Grade Group according to the 2014 International Society of Urological Pathology guidelines, without incorporation of IDC in grading. Tumour grading was compared with a Grade Group in which IDC was graded on the basis of its underlying architecture. Of 1031 biopsies, 139 (13.5%) showed IDC. Grade assignment of IDC led to a Grade Group change in 17 (1.6%) cases: four of 486 (0.8%) Grade Group 1 cases were reclassified as Grade Group 2, nine of 375 (2.4%) Grade Group 2 cases were reclassified as Grade Group 3, and four of 58 (6.9%) Grade Group 4 cases were reclassified as Grade Group 5. IDC was observed in 213 of 835 (25.5%) radical prostatectomies, and its grading led to a change in tumour grade in five of 835 (0.6%) patients, with upgrading in two of 207 (1.0%) patients with Grade Group 1 cancer, in two of 420 (0.5%) patients with Grade Group 2 cancer, and in one of 50 (2%) patients with Grade Group 4 cancer.

CONCLUSION: IDC grade assignment led to a Grade Group change in 1.6% of prostate biopsy specimens and in 0.6% of radical prostatectomy specimens. Although the inclusion of IDC in or the exclusion of IDC from the Grade Group might affect decision-making in individual patients, it has a minimal impact on overall prostate cancer management.}, } @article {pmid32541178, year = {2020}, author = {Kono, H and Maeda, H and Yao, S and Takahashi, M and Yokoi, S and Goi, T and Imamura, Y}, title = {[Conversion Therapy for HER2-Positive Metastatic Breast Cancer with Intrathoracic Lymph Node Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {6}, pages = {977-980}, pmid = {32541178}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; Mastectomy ; Neoplasm Recurrence, Local ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 42-year-old woman consulted our hospital with chief complaints of a right breast mass and pain. Based on needle biopsy of the breast tumor, the pathological diagnosis was invasive ductal carcinoma(scirrhous type), which tested positive for estrogen, progesterone, and HER2 receptor. PET-CT(FDG)showed intrathoracic lymph node metastasis. After several tests, she received a diagnosis of cT2N1M1(LYM), Stage Ⅳ breast cancer. She received pertuzumab, trastuzumab, and docetaxel treatments. After chemotherapy, the intrathoracic lymph node and breast tumors were not observed. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis showed a complete response after surgery. The patient's postoperative course was uneventful; she had received radiotherapy and anti-HER2 therapy. Twenty-three months after the surgery, no recurrence was observed. Herein, we report successful treatment of Stage Ⅳ breast cancer with conversion therapy.}, } @article {pmid32539751, year = {2020}, author = {Hedrick, K and Armstrong, G and Coffey, G and Borschmann, R}, title = {An evaluation of the quality of self-harm incident reporting across the Australian asylum seeker population according to World Health Organization (WHO) guidelines.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {301}, pmid = {32539751}, issn = {1471-244X}, support = {N/A//Australian government Post-Graduate Research Training Grant/International ; #1104464//National Health and Medical Research Council/International ; #1138096//National Health and Medical Research Council (AU)/International ; }, mesh = {Australia/epidemiology ; Humans ; *Refugees ; Risk Management ; *Self-Injurious Behavior/epidemiology ; World Health Organization ; }, abstract = {BACKGROUND: Asylum seekers are at elevated risk of self-harm, and the personal and public health costs of self-harm are high; yet the monitoring and reporting of self-harm has been limited and lacking in transparency. This study aims to evaluate the quality of self-harm incident reporting across the Australian asylum seeker population, including by processing arrangements (i.e. community-based, community detention, onshore detention, Nauru, and Manus Island).

METHODS: All self-harm incidents reported across the entire Australian asylum seeker population between 1 August 2014 and 31 July 2015 were obtained via the Freedom of Information Act. We assessed the quality of self-harm incident reporting according to the World Health Organization (WHO)'s self-harm reporting guidelines.

RESULTS: A total of 949 self-harm incident reports were assessed. Date, location (processing arrangement), and time of self-harm were routinely reported. Gender was recorded in less than two thirds (62.1%) of all incidents. Method(s) used to self-harm was reported in 81.5% of all incidents, though IDC-10 codes were not reported in any episodes. Psychological or psychiatric assessments were recorded after 4.0% of all incidents, most frequently on Manus Island (10.9%), and in Nauru (10.0%), and least frequently in community-based arrangements (1.7%) and in onshore detention (1.4%), and not at all in community detention. Ambulances were reported as attending 2.8% of all episodes. Hospital attendances were reported following 6.0% of all self-harm incidents, with attendances most commonly reported in incidents occurring in community detention (30.3%), and in community-based arrangements (19.4%). Medevac (air ambulances) were recorded as being utilised in 0.4% of all incidents (2.1% of episodes on Nauru, 1.8% on Manus Island).

CONCLUSIONS: The findings of our study indicate that the accessibility and quality of self-harm data is substandard and inconsistent with WHO self-harm reporting guidelines. Such variable reporting makes the identification of self-harm trends, the implementation of prevention strategies - including those at a policy level - and the clinical management of self-harm, extremely challenging. Improved self-harm reporting and monitoring is urgently needed for mitigating and responding to self-harm risk among asylum seekers.}, } @article {pmid32537791, year = {2020}, author = {Lim, GH and Gudi, M and Teo, SY and Ng, RP and Yan, Z and Lee, YS and Allen, JC and Leong, LCH}, title = {Would Removal of All Ultrasound Abnormal Metastatic Lymph Nodes Without Sentinel Lymph Node Biopsy Be Accurate in Patients with Breast Cancer with Neoadjuvant Chemotherapy?.}, journal = {The oncologist}, volume = {25}, number = {11}, pages = {e1621-e1627}, pmid = {32537791}, issn = {1549-490X}, mesh = {Axilla/pathology ; *Breast Neoplasms/pathology ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/diagnostic imaging/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; *Sentinel Lymph Node/diagnostic imaging/pathology ; *Sentinel Lymph Node Biopsy ; }, abstract = {LESSONS LEARNED: Removal of sonographically abnormal (up to 3) metastatic clipped nodes, without sentinel lymph node biopsy, could accurately predict axillary status in breast cancer patients receiving neoadjuvant chemotherapy. ypT and the first clipped node status were statistically significant factors for nodal pathologic complete response. This novel approach requires validation in larger studies.

BACKGROUND: In patients who have node-positive breast cancer, neoadjuvant chemotherapy could result in nodal pathologic complete response (pCR) and avoid an axillary lymph node dissection (ALND). Axillary staging, in such cases, can be performed using targeted axillary dissection (TAD) with a low false negative rate. However, identification of sentinel lymph nodes (SLNs) after chemotherapy can be difficult, and currently, it is the standard to remove only one clipped node in TAD. We aimed to determine if removal of all sonographically abnormal metastatic clipped nodes, without SLN biopsy, could accurately predict the axillary status post neoadjuvant chemotherapy.

METHODS: Patients with breast cancer with one to three sonographically abnormal metastatic axillary nodes were prospectively recruited. Each abnormal node had histology and clip insertion before neoadjuvant chemotherapy. After chemotherapy, the patients underwent removal of clipped nodes using the Skin Mark clipped Axillary nodes Removal Technique (SMART) and ALND.

RESULTS: Fourteen patients were recruited, having a total of 21 sonographically abnormal metastatic nodes, with nine, three, and two patients having 1, 2, and 3 malignant nodes clipped, respectively. Mean age was 55.5 years; 92.9% and 57.1% of patients had invasive ductal carcinoma and grade III tumors, respectively; and 35.7% patients achieved nodal pCR. The first clipped node predicted the axillary status with a false negative rate of 7.1%. Adding to this another second clipped node, the false negative rate was 0%. Pathologic tumor staging after neoadjuvant chemotherapy (ypT) (p = .0390) and the first clipped node pathological response status (p = .0030) were statistically significant predictors for nodal pCR.

CONCLUSION: Removal of sonographically abnormal metastatic clipped nodes using SMART, without sentinel lymph node biopsy, could accurately predict axillary status. This finding needs validation in larger studies.}, } @article {pmid32535256, year = {2020}, author = {Strang, LR and Sun, J and Sun, W and Boulware, D and Kiluk, JV and Lee, MC and Khazai, L and Laronga, C}, title = {Characteristics of Microinvasive Ductal Carcinoma In Situ Versus Noninvasive and Invasive Breast Cancer.}, journal = {The Journal of surgical research}, volume = {254}, number = {}, pages = {378-383}, doi = {10.1016/j.jss.2020.04.031}, pmid = {32535256}, issn = {1095-8673}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*pathology ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS.

METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves.

RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence.

CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.}, } @article {pmid32532588, year = {2020}, author = {Brings, S and Fleming, T and Herzig, S and Nawroth, PP and Kopf, S}, title = {Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study.}, journal = {Journal of diabetes and its complications}, volume = {34}, number = {9}, pages = {107648}, doi = {10.1016/j.jdiacomp.2020.107648}, pmid = {32532588}, issn = {1873-460X}, mesh = {*Albuminuria/diagnosis/etiology ; Cathepsin D/urine ; Cathepsin L/*urine ; Cohort Studies ; *Diabetes Mellitus, Type 2/complications/diagnosis ; *Glycation End Products, Advanced/urine ; Humans ; Tandem Mass Spectrometry ; }, abstract = {AIMS: Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study.

METHODS: We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients.

RESULTS: The detection limit of CTSD and CTSL in urine was 2.4 ng/l and 19.1 ng/l, respectively. CTSD (p < 0.0001, r = 0.555) and CTSL (p < 0.0001, r = 0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p = 0.012, r = 0.225; CTSL: p < 0.001, r = 0.376). A strong non-linear association between CTSD (r = 0.568), CTSL (r = 0.588) and change in albuminuria over four years was present. High levels of CTSL (p = 0.007, beta = -0.366) were associated with an improvement of albuminuria after four years.

CONCLUSIONS: A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.}, } @article {pmid32528739, year = {2020}, author = {Kanteti, AP and Atiya, S and Hein, A and Cox, JL and Martinez Duarte, E}, title = {Medullary Thyroid Carcinoma Presenting as Metastatic Disease to the Breast.}, journal = {Case reports in pathology}, volume = {2020}, number = {}, pages = {6138409}, pmid = {32528739}, issn = {2090-6781}, abstract = {Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that is derived from C cells of the thyroid gland. It is a rare aggressive tumor, known to metastasize to lymph nodes, liver, bones, and lungs. A 41-year-old female, who presented with a breast mass, was initially diagnosed with invasive ductal carcinoma. She was also found to have a thyroid mass which was later diagnosed as MTC. On a rereview of the breast pathology, the morphologic features were strikingly similar to the MTC. Further investigation revealed that this was in fact a very rare case of MTC that had metastasized to the breast. We have identified 20 cases of MTC metastasizing to the breast in the literature that supports its occurrence as a real possibility. Albeit rare, medullary thyroid carcinoma should be considered in the differential diagnosis of a breast mass.}, } @article {pmid32524658, year = {2020}, author = {Kang, SR and Kim, HW and Kim, HS}, title = {Evaluating the Relationship Between Dynamic Contrast-Enhanced MRI (DCE-MRI) Parameters and Pathological Characteristics in Breast Cancer.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {52}, number = {5}, pages = {1360-1373}, doi = {10.1002/jmri.27241}, pmid = {32524658}, issn = {1522-2586}, mesh = {*Breast Neoplasms/diagnostic imaging ; Contrast Media ; Humans ; Magnetic Resonance Imaging ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) is used to evaluate tumor microvasculature. However, studies demonstrating an association between perfusion parameters derived from DCE-MRI and histopathologic characteristics are limited to a small set of histopathologic factors, and the results are inconsistent.

PURPOSE: To evaluate the relationship between DCE-MRI perfusion parameters and common histopathologic tumor characteristics used to predict angiogenesis and determine prognosis in breast cancer.

STUDY TYPE: Retrospective.

POPULATION: In all, 105 breast cancer patients with invasive ductal carcinoma (122 lesions).

FIELD STRENGTH/SEQUENCE: 3.0T, turbo spin-echo (TSE) T1 -weighted, fat-suppressed T2 -weighted, TSE T2 -weighted, and dynamic unenhanced and contrast-enhanced 3D T1 high-resolution isotropic volume examination.

ASSESSMENT: One reviewer obtained perfusion parameters (K[trans] , kep , ve , and vp) of each breast cancer from DCE MRI using the extended Tofts model with a fixed baseline T1 value and a population-based arterial input function. The relationship between DCE-MRI perfusion parameters and histopathologic tumor characteristics used to predict angiogenesis and determine prognosis was evaluated.

STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, analysis of variance (ANOVA), and Kruskal-Wallis test were used.

RESULTS: Triple-negative breast cancers exhibited higher K[trans] and kep than luminal cancers (P < 0.05). Estrogen receptor (ER)-negative tumors showed higher K[trans] than ER-positive tumors (P < 0.05). Progesterone receptor (PR)-negative tumors presented higher ve than PR-positive tumors (P < 0.05). Tumors with higher Ki-67 showed higher kep than tumors with lower Ki-67 (P < 0.05). P53-positive tumors exhibited higher K[trans] and kep than p53-negative tumors (P < 0.05). Higher histologic grade tumors (grade II/III) presented higher K[trans] , kep , vp (P < 0.05) than grade I tumors. Tumors with LVSI presented higher K[trans] and kep than tumors without LVSI (P < 0.05).

DATA CONCLUSION: Breast cancer presenting higher K[trans] and kep on DCE-MRI was associated with poor prognostic histopathologic factors. Therefore, pretreatment DCE-MRI perfusion parameters may be useful imaging biomarkers for the evaluation of tumor prognosis and angiogenesis.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.}, } @article {pmid32522804, year = {2020}, author = {Zhang, P and Wu, X and Gardashova, G and Yang, Y and Zhang, Y and Xu, L and Zeng, Y}, title = {Molecular and functional extracellular vesicle analysis using nanopatterned microchips monitors tumor progression and metastasis.}, journal = {Science translational medicine}, volume = {12}, number = {547}, pages = {}, pmid = {32522804}, issn = {1946-6242}, support = {R01 CA260132/CA/NCI NIH HHS/United States ; R21 EB024101/EB/NIBIB NIH HHS/United States ; P20 GM103638/GM/NIGMS NIH HHS/United States ; R01 CA243445/CA/NCI NIH HHS/United States ; R21 CA207816/CA/NCI NIH HHS/United States ; R33 CA214333/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA191785/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Breast Neoplasms ; *Extracellular Vesicles ; Female ; Humans ; Lab-On-A-Chip Devices ; Liquid Biopsy ; Mice ; Precision Medicine ; }, abstract = {Longitudinal cancer monitoring is crucial to clinical implementation of precision medicine. There is growing evidence indicating important functions of extracellular vesicles (EVs) in tumor progression and metastasis, including matrix remodeling via transporting matrix metalloproteases (MMPs). However, the clinical relevance of EVs remains largely undetermined, partially owing to challenges in EV analysis. Distinct from existing technologies mostly focused on characterizing molecular constituents of EVs, here we report a nanoengineered lab-on-a-chip system that enables integrative functional and molecular phenotyping of tumor-associated EVs. A generalized, high-resolution colloidal inkjet printing method was developed to allow robust and scalable manufacturing of three-dimensional (3D) nanopatterned devices. With this nanochip platform, we demonstrated integrative analysis of the expression and proteolytic activity of MMP14 on EVs to detect in vitro cell invasiveness and monitor in vivo tumor metastasis, using cancer cell lines and mouse models. Analysis of clinical plasma specimen showed that our technology could be used for cancer detection including accurate classification of age-matched controls and patients with ductal carcinoma in situ, invasive ductal carcinoma, or locally metastatic breast cancer in a training cohort (n = 30, 96.7% accuracy) and an independent validation cohort (n = 70, 92.9% accuracy). With clinical validation, our technology could provide a useful liquid biopsy tool to improve cancer diagnostics and real-time surveillance of tumor evolution in patients to inform personalized therapy.}, } @article {pmid32516333, year = {2020}, author = {Rudnev, M and Vauclair, CM and Aminihajibashi, S and Becker, M and Bilewicz, M and Castellanos Guevara, JL and Collier-Baker, E and Crespo, C and Eastwick, P and Fischer, R and Friese, M and Gomez, A and Guerra, V and Hanke, K and Hooper, N and Huang, LL and Karasawa, M and Kuppens, P and Loughnan, S and Peker, M and Pelay, C and Pina, A and Sachkova, M and Saguy, T and Shi, J and Silfver-Kuhalampi, M and Sortheix, F and Swann, W and Tong, JY and Yeung, VW and Bastian, B}, title = {Measurement invariance of the moral vitalism scale across 28 cultural groups.}, journal = {PloS one}, volume = {15}, number = {6}, pages = {e0233989}, pmid = {32516333}, issn = {1932-6203}, mesh = {Adult ; Americas ; Asia ; Australia ; Cross-Cultural Comparison ; Europe ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mexico ; *Morals ; New Zealand ; Psychometrics/methods ; United States ; Venezuela ; Vitalism/*psychology ; Young Adult ; }, abstract = {Moral vitalism refers to a tendency to view good and evil as actual forces that can influence people and events. The Moral Vitalism Scale had been designed to assess moral vitalism in a brief survey form. Previous studies established the reliability and validity of the scale in US-American and Australian samples. In this study, the cross-cultural comparability of the scale was tested across 28 different cultural groups worldwide through measurement invariance tests. A series of exact invariance tests marginally supported partial metric invariance, however, an approximate invariance approach provided evidence of partial scalar invariance for a 5-item measure. The established level of measurement invariance allows for comparisons of latent means across cultures. We conclude that the brief measure of moral vitalism is invariant across 28 cultures and can be used to estimate levels of moral vitalism with the same precision across very different cultural settings.}, } @article {pmid32512721, year = {2020}, author = {Sarhadi, S and Salehzadeh-Yazdi, A and Damaghi, M and Zarghami, N and Wolkenhauer, O and Hosseini, H}, title = {Omics Integration Analyses Reveal the Early Evolution of Malignancy in Breast Cancer.}, journal = {Cancers}, volume = {12}, number = {6}, pages = {}, pmid = {32512721}, issn = {2072-6694}, abstract = {The majority of cancer evolution studies involve individual-based approaches that neglect the population dynamics necessary to build a global picture of cancer evolution for each cancer type. Here, we conducted a population-based study in breast cancer to understand the timing of malignancy evolution and its correlation to the genetic evolution of pathological stages. In an omics integrative approach, we integrated gene expression and genomic aberration data for pre-invasive (ductal carcinoma in situ; DCIS, early-stage) and post-invasive (invasive ductal carcinoma; IDC, late-stage) samples and investigated the evolutionary role of further genetic changes in later stages compared to the early ones. We found that single gene alterations (SGAs) and copy-number alterations (CNAs) work together in forward and backward evolution manners to fine-tune the signaling pathways operating in tumors. Analyses of the integrated point mutation and gene expression data showed that (i) our proposed fine-tuning concept is also applicable to metastasis, and (ii) metastases sometimes diverge from the primary tumor at the DCIS stage. Our results indicated that the malignant potency of breast tumors is constant over the pre- and post-invasive pathological stages. Indeed, further genetic alterations in later stages do not establish de novo malignancy routes; however, they serve to fine-tune antecedent signaling pathways.}, } @article {pmid32512360, year = {2020}, author = {Yang, X and Huang, J and Zhu, X and Shen, K and Zhu, J and Chen, X}, title = {Compliance with multidisciplinary team recommendations and disease outcomes in early breast cancer patients: An analysis of 4501 consecutive patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {52}, number = {}, pages = {135-145}, pmid = {32512360}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/*therapy ; China/epidemiology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; *Patient Care Team ; Retrospective Studies ; Treatment Adherence and Compliance/*statistics & numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Multidisciplinary team (MDT) discussions are widely held to facilitate the diagnosis and treatment of breast cancer, but patient compliance with the MDT recommendations and the impact of compliance on disease outcome are uncertain.

METHODS: We conducted a retrospective review of data from a prospective database of breast cancer patients treated at Shanghai Ruijin Hospital between April 2013 and August 2018. MDT discussions were held for all patients before they started adjuvant therapy. The patients were classified into compliant and non-compliant groups according to whether they received the MDT-recommended regimens. We also analyzed which clinicopathological factors were associated with compliance and prognosis.

RESULTS: Of 4501 breast cancer patients, 3681 (81.8%) and 820 (18.2%) were included in the compliant and non-compliant groups, respectively. Age >70 years (P < 0.001), invasive ductal carcinoma (P < 0.001), and histological grade III (P = 0.011) were independently associated with higher risk of non-compliance, whereas Ki-67 labeling index ≥14% and history of benign breast disease were independently associated with compliance. Disease-free survival (hazard ratio [HR] 1.813, 95% confidence interval [CI] 1.367-2.405, P < 0.001) and overall survival (HR 2.478, 95% CI 1.431-4.291, P < 0.001) were worse in the non-compliant group.

CONCLUSIONS: Several clinicopathological factors were associated with non-compliance with MDT recommendations for early breast cancer patients. Non-compliance was associated with worse disease outcome.}, } @article {pmid32511899, year = {2020}, author = {Yamaguchi, T and Akahane, T and Harada, O and Kato, Y and Aimono, E and Takei, H and Tasaki, T and Noguchi, H and Nishihara, H and Kamata, H and Tanimoto, A}, title = {Next-generation sequencing in residual liquid-based cytology specimens for cancer genome analysis.}, journal = {Diagnostic cytopathology}, volume = {48}, number = {11}, pages = {965-971}, doi = {10.1002/dc.24511}, pmid = {32511899}, issn = {1097-0339}, mesh = {Carcinoma/*genetics ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*methods ; Gene Frequency/genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lymph Nodes/pathology ; Mutation/genetics ; Neoplasms/*genetics ; Sequence Analysis, DNA/methods ; Thyroid Gland/pathology ; }, abstract = {BACKGROUND: Cancer genome profiling of cytology specimens using next-generation sequencing (NGS) requires adequate and good-quality DNA. Genomic examination of cytology samples was conventionally performed on cell block (CB) or smear specimens than on residual liquid-based cytology (LBC) specimens, which are high-quality DNA sources even after long-term storage.

METHODS: We estimated tumor fractions of 37 residual LBC specimens, including 30 fine needle aspiration (FNA) samples from the thyroid (12 papillary thyroid carcinomas and two malignant lymphomas), lymph node (13 metastatic carcinomas and one malignant lymphoma), and breast cancer (one phyllodes tumor and one invasive ductal carcinoma), two pancreatic carcinoma samples, and five liquid (ascites, pleural effusion, and cerebrospinal fluid) samples. The DNA was extracted from all samples and subjected to NGS using a customized cancer gene panel comprising 28 cancer-related genes.

RESULTS: NGS analysis revealed somatic mutations corresponding to pathological diagnosis with adequate variant allele frequency (VAF) in 24 LBC specimens, which had significantly higher tumor fraction (72.5% ± 4.9%). Ten cases, including the five fluid samples, had very small tumor fractions (7.5% ± 2.3%) to obtain sufficient VAF. Other two samples had high tumor fractions but showed very low VAF, indicating the presence of fusion genes. The remaining one sample yielded no DNA recovery.

CONCLUSION: The residual LBC specimens collected by FNA from the thyroid gland and lymph node were verified to carry high tumor fraction and could serve as an alternate source for molecular testing to screen and diagnose cancers without the use of CB or smears.}, } @article {pmid32509097, year = {2020}, author = {Lv, X and Ye, J and Jiang, G and Wang, Y and Lv, J and Wang, Y}, title = {Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {13}, number = {5}, pages = {1212-1215}, pmid = {32509097}, issn = {1936-2625}, abstract = {Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.}, } @article {pmid32509080, year = {2020}, author = {Liu, BT and Ding, JN and Wang, JL and Li, ZS and Ding, YL and Ma, R}, title = {Differences in pathologic characteristics between ductal carcinoma in situ (DCIS), DCIS with microinvasion and DCIS with invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {13}, number = {5}, pages = {1066-1072}, pmid = {32509080}, issn = {1936-2625}, abstract = {In order to further our understanding of pathologic features in various ductal carcinoma in situ (DCIS) related breast ductal cancers, including DCIS, DCIS with microinvasion (DCIS-Mi) and DCIS with invasive ductal carcinoma (DCIS-IDC), a retrospective study including 453 cases of DCIS, 88 cases of DCIS-Mi, and 269 cases of DCIS-IDC was conducted. Statistical analysis showed significant pathological differences were found in DCIS, DCIS-Mi, and DCIS-IDC. Compared with DCIS, DCIS-IDC was significantly more associated with high nuclear grade, large tumor size, high Ki67 index, and lymph node metastasis (all P<0.05). Higher expression of steroid receptors was shown in DCIS-IDC than in DCIS (all P<0.05), but the status of HER2 between the two groups was similar (P=0.269). Compared with DCIS, DCIS-Mi was significantly more associated with high nuclear grade, large tumor size, comedonecrosis, absence of steroid receptors, HER2 overexpression, and high Ki67 index (all P<0.05). These features remain consistently even when compared with DCIS-IDC. According to the immunohistochemistry surrogate classification, the dominant types of DCIS and DCIS-IDC were luminal types (luminal A and luminal B, respectively), while the dominant type of DCIS-Mi was HER2 overexpression. These findings suggest that DCIS-Mi represents a distinct entity, and DCIS with features including high nuclear grade, large tumor size, comedonecrosis, steroid receptors negativity, HER2 positivity, and high Ki67 expression was more likely to have microinvasion than DCIS without these features.}, } @article {pmid32507956, year = {2020}, author = {Akhtar, Z and Stearns, V and Cartwright, P and Blackford, AL and Prasath, V and Klein, C and Jelovac, D and Asrari, F and Habibi, M}, title = {The effect of 1-day multidisciplinary clinic on breast cancer treatment.}, journal = {Breast cancer research and treatment}, volume = {182}, number = {3}, pages = {623-629}, doi = {10.1007/s10549-020-05721-3}, pmid = {32507956}, issn = {1573-7217}, mesh = {Breast Neoplasms/diagnosis/*drug therapy ; Delivery of Health Care/*methods/standards ; Female ; Follow-Up Studies ; Humans ; Interdisciplinary Communication ; Middle Aged ; Neoadjuvant Therapy ; Outcome Assessment, Health Care ; Patient Care Team/*organization & administration ; Prognosis ; Quality Improvement ; Retrospective Studies ; Survival Rate ; Time-to-Treatment ; }, abstract = {PURPOSE: A delay in breast cancer treatment is associated with inferior survival outcomes; however, no clear guidelines exist defining the appropriate time frame from diagnosis to definitive treatment of breast cancer. A multidisciplinary approach for breast cancer treatment can minimize the time from diagnosis to first treatment. We hypothesized single-day multidisciplinary clinic (MDC) may accelerate the time to first treatment on complex breast cancer cases at our institution.

METHODS: We identified patients who were treated at Johns Hopkins for stage II or III breast cancer, who were at least 18 years of age, and were seen in a new single-day MDC with coordination between two or three specialties or by specialists from varying disciplines on different days (IDC). Patients who initiated treatment between May 2015 (initiation of MDC clinic) and December 2017 were included in our study.

RESULTS: A total of 296 patient records were reviewed independently. The mean (SD) patient age was 55 (13) years. The median time to first neoadjuvant chemotherapy (NACT) was significantly reduced for patients seen in the MDC (12.7 days), compared to those seen at the IDC (24.4 days, logrank p < 0.001). The median time to definitive surgery was similar between groups (31 and 32 days for the MDC and IDC cohorts, respectively).

CONCLUSIONS: A single-day MDC visit is associated with a reduced time from diagnosis to NACT. Further studies are needed to determine if a shorter interval can improve the management and the outcome of complex breast cancer cases.}, } @article {pmid32502770, year = {2020}, author = {Gest, R and Cayet, S and Arbion, F and Vildé, A and Body, G and Ouldamer, L}, title = {Predictive factors of major deviation (>20 mm) between lesion sizes measured by magnetic resonance imaging and histology for invasive lobular breast cancer.}, journal = {European journal of obstetrics, gynecology, and reproductive biology}, volume = {251}, number = {}, pages = {14-19}, doi = {10.1016/j.ejogrb.2020.05.036}, pmid = {32502770}, issn = {1872-7654}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Lobular/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; }, abstract = {OBJECTIVE: To identify factors predictive of high discordance (>20 mm) between lesion sizes measured by magnetic resonance imaging (MRI) and histology for invasive lobular breast cancer.

MATERIALS AND METHODS: Data for all women with invasive lobular breast cancer (pure or associated with a component of invasive ductal carcinoma) between 1st January 2007 and 31st December 2016 were included in this study. Logistic regression analysis was performed to determine factors predictive of high discordance (underestimation/overestimation by >20 mm) between tumour sizes measured by MRI and histology for invasive lobular breast cancer.

RESULTS: For overestimation, significant factors on univariate analysis were: menopausal status [odds ratio (OR) 0.27, 95 % confidence interval (CI) 0.10-0.71]; p = 0.01], hormone receptor (HR) status (HR negative, OR 1.64, 95 % CI 0.27-9.89; HR positive, OR 0.64, 95 % CI 0.21-1.88; p = 0.09) and neoadjuvant chemotherapy (OR 10.33, 95 % CI 3.58-29.8; p < 0.001). On multivariate analysis, menopausal status and neoadjuvant chemotherapy were found to be independent predictive factors of overestimation. For underestimation, significant factors on univariate analysis were: histological size (OR 1.05, 95 % CI 1.02-1.08; p < 0.0001) and the presence of an in-situ component (OR 4.66, 95 % CI 1.01-21.5; p = 0.02). These two factors were independent predictive factors of underestimation.

CONCLUSION: Independent predictive factors of overestimation/underestimation (threshold 20 mm) of tumour sizes measured by MRI compared with histology for invasive lobular breast cancer were identified.}, } @article {pmid32500174, year = {2020}, author = {Li, J and Yuan, M and Yang, L and Guo, L}, title = {Correlation of contrast-enhanced ultrasound features with prognostic factors in invasive ductal carcinomas of the breast.}, journal = {Japanese journal of radiology}, volume = {38}, number = {10}, pages = {960-967}, pmid = {32500174}, issn = {1867-108X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; *Contrast Media ; DNA Topoisomerases, Type II/metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Phospholipids ; Poly-ADP-Ribose Binding Proteins/metabolism ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sulfur Hexafluoride ; *Ultrasonography ; }, abstract = {OBJECTIVES: To correlate contrast-enhanced ultrasound (CEUS) features with pathological prognostic factors of breast invasive ductal carcinomas (IDCs).

METHODS: 169 patients who were admitted to our hospital with confirmed IDCs diagnosed between August 2017 and June 2019 were selected. CEUS indicators included the time of contrast agent entered the lesion, the degree of enhancement, the boundary of the lesion, whether there was perfusion defect and nourishing blood vessels, and etc. These parameters correlated with traditional prognostic factors (tumour size, histological grade, axillary lymph node status) and immunohistochemical biomarkers (ER, PR, c-erbB-2, Ki-67, and TOPO-II).

RESULTS: Perfusion defects after enhancement were predictive factors of PR negative expression (r = - 0.318, OR = 0.239) and TOPO-II overexpression (r = 0.284, OR = 3.577). Centripetal enhancement was negatively correlated with ER expression (r = - 0.350, OR = 0.246). The lesions with a larger range after enhancement than the conventional ultrasound had a higher histological grade (r = 0.215). Perfusion defects were positively correlated with lymph node metastasis (r = 0.221) and negatively correlated with the expression of ER and PR (r = - 0.342, r = - 0.318).

CONCLUSIONS: Contrast-enhanced ultrasound features of IDCs have a certain correlation with pathological prognostic factors, which is conducive in assessing the prognosis of these patients.}, } @article {pmid32496222, year = {2021}, author = {Zhang, YC and Sun, GL and Ma, DL and Wei, C and Shang, HJ and Liu, Z and Li, R and Wang, T and Wang, SG and Liu, JH and Liu, XM}, title = {The presence of intraductal carcinoma of the prostate is closely associated with poor prognosis: a systematic review and meta-analysis.}, journal = {Asian journal of andrology}, volume = {23}, number = {1}, pages = {103-108}, pmid = {32496222}, issn = {1745-7262}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Humans ; Male ; Prognosis ; Prostatic Neoplasms/*diagnosis/pathology ; Treatment Outcome ; }, abstract = {We aimed to confirm the predictive ability of the presence of intraductal carcinoma of the prostate (IDC-P) for prognosis and the associations between IDC-P and clinicopathological parameters. Studies were identified in PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS up to December 1, 2019. Hazard ratios (HRs) for survival data and odds ratios for clinicopathological data with 95% confidence intervals (CIs) were extracted. Heterogeneity was evaluated by the I[[2]] value, and quality was assessed by the Newcastle-Ottawa Scale criteria. A total of 4179 patients from 13 studies were included. The results showed that IDC-P presence was significantly associated with poor progression-free survival (PFS; HR = 2.31; 95% CI: 1.96-2.73), cancer-specific survival (HR = 1.89; 95% CI: 1.28-2.77), and overall survival (HR = 2.14; 95% CI: 1.53-3.01). In the subgroup analysis, IDC-P presence was significantly associated with poor PFS in prostate cancer treated by radical prostatectomy (HR = 2.48; 95% CI: 2.05-3.00) and treated by radiotherapy (HR = 2.83; 95% CI: 1.65-4.85). Regarding clinicopathological characteristics, patients with IDC-P presence had significantly higher tumor clinical stages, Gleason scores, probabilities of lymph node invasion, positive surgical margins, and positive extraprostatic extension. Our meta-analysis indicates that the presence of IDC-P is closely associated with poor prognosis and adverse clinicopathological characteristics. Our data support the value and clinical utility of the routine detection of IDC-P by pathological examination. These conclusions need further validation, and prospective studies are needed to find better treatment modalities other than traditional first-line therapy for patients with IDC-P.}, } @article {pmid32493703, year = {2020}, author = {O'Keefe, TJ and Blair, SL and Hosseini, A and Harismendy, O and Wallace, AM}, title = {HER2-Overexpressing Ductal Carcinoma In Situ Associated with Increased Risk of Ipsilateral Invasive Recurrence, Receptor Discordance with Recurrence.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {13}, number = {9}, pages = {761-772}, pmid = {32493703}, issn = {1940-6215}, support = {P30 CA023100/CA/NCI NIH HHS/United States ; U01 CA196406/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Biomarkers, Tumor/analysis/*metabolism ; Breast/*pathology/surgery ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/*epidemiology/pathology ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; SEER Program/statistics & numerical data ; }, abstract = {The impact of HER2 status in ductal carcinoma in situ (DCIS) on the risk of progression to invasive ductal carcinoma (IDC) has been debated. We aim to use a national database to identify patients with known HER2 status to elucidate the effect of HER2 overexpression on ipsilateral IDC (iIDC) development. We performed survival analysis on patient-level data using the U.S. NCI's Surveillance Epidemiology and End Results program. We identified patients diagnosed with DCIS who underwent lumpectomy and had known HER2 status. Competing risks analysis was performed. A total of 1,540 patients had known HER2 status and met inclusion criteria. Median age at diagnosis was 60, median follow-up time was 44.5 months. A total of 417 (27.1%) patients were HER2 positive and 1,035 (67.2%) were HER2 negative. Twenty-two (1.4%) patients developed iIDC and 27 (1.8%) developed ipsilateral in situ or contralateral disease. The estimated cumulative incidence of iIDC at 5 years was 1.9% for all patients, 1.2% for HER2-negative and borderline patients, and 3.9% for HER2-positive patients. On multivariate competing risks regression, two factors were significant for iIDC: radiation (protective) therapy within 24 months (HR, 0.05; P = 0.00006) and HER2 overexpression (increased likelihood; HR, 2.72; P = 0.044). Patients with HER2-positive DCIS were more likely to have recurrences with receptor discordance. HER2 may serve as a prognostic factor for invasive recurrence and was the only lesion-related factor to significantly relate to iIDC development. It may also be associated with receptor discordance of recurrences. Further large studies will be needed to confirm these results.}, } @article {pmid32493607, year = {2021}, author = {Oliver Guillén, JR and Hernando Almudi, E and Molina Osorio, G and Ibañez Carreras, R and Font Gómez, JA and Vicente Gómez, I and García Mur, C and Casamayor Franco, MC}, title = {Intraoperative radiotherapy in early breast cancer: observational comparison with whole breast radiotherapy.}, journal = {Cirugia espanola}, volume = {99}, number = {2}, pages = {132-139}, doi = {10.1016/j.ciresp.2020.04.024}, pmid = {32493607}, issn = {2173-5077}, abstract = {INTRODUCTION: In early breast cancer (EBC), a single dose of intraoperative radiotherapy (IORT) might be an option to standard whole breast radiotherapy (WBRT). However, there is no consensus about its use and clinical results.

AIM: to analyse the morbidity and oncological outcomes of IORT as monotherapy in EBC.

METHODS: A single centre observational analytic study was performed. A prospective IORT cohort (2015-17) and a retrospective WBRT cohort (2012-17) were selected following the same criteria: ≥ 45 y.o., invasive ductal carcinoma or variants, radiological tumour size ≤ 3 cm, positive oestrogenic receptors, negative HER2, cN0; exclusion criteria: lymphovascular invasion, multicentricity/multifocality, BRCA mutation and neoadjuvant therapy. Clinical, histological, surgical, oncological characteristics and complications were collected.

RESULTS: A total of 425 cases were selected: 217 in IORT cohort and 208 in WBRT cohort. Average age in IORT and WBRT groups was 67±9.5 and 64.8 ± 9.9 y.o. respectively (p = 0.01). ASA 3 risk score patients were 17.7% in IORT and 24 cases in WBRT (p = 0.027). There were no differences in histological results or tumoral stage. Average follow up was 24.4 ± 8 months in IORT and 50.5 ± 18 months in WBRT (p < 0.001). No differences were detected in local recurrence, metastases or mortality. Complications that required reintervention or hospitalization were similar in both groups. A total of 3 and 14 cases developed early severe dermatitis in IORT and WBRT groups respectively (p = 0.01).

CONCLUSION: IORT as monotherapy in selected patients with EBC stands for an alternative option versus WBRT. It seems especially useful in advanced-age patients with severe comorbidities. IORT associates lesser early severe dermatitis.}, } @article {pmid32493410, year = {2020}, author = {Takada, K and Kashiwagi, S and Asano, Y and Goto, W and Morisaki, T and Takahashi, K and Fujita, H and Takashima, T and Tomita, S and Hirakawa, K and Ohira, M}, title = {Factors predictive of invasive ductal carcinoma in cases preoperatively diagnosed as ductal carcinoma in situ.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {513}, pmid = {32493410}, issn = {1471-2407}, support = {19K18067//Japan Society for the Promotion of Science/ ; 17K10559//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Biopsy, Large-Core Needle ; Breast/*pathology/surgery ; Breast Neoplasms/blood/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/blood/*diagnosis/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/blood/*diagnosis/pathology/surgery ; Female ; Humans ; L-Lactate Dehydrogenase/blood ; Lymphatic Metastasis ; Lymphocyte Count ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness/diagnosis/pathology ; Platelet Count ; Postoperative Period ; Preoperative Period ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy.

METHODS: In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15-3 (CA15-3). The platelet-lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (< 160.0) groups.

RESULTS: Invasion was found more frequently after surgery in pathologically high-grade cases than in pathologically not-high-grade cases (p = 0.015). The median PLR was 138.9 and 48 patients (40.7%) were classified into the high PLR group. The high PLR group was significantly more likely to have invasion detected by the postoperative pathology than the low PLR group (p = 0.018). In multivariate analysis of factors predictive of invasion in postoperative pathology, a high PLR (p = 0.006, odds ratio [OR] = 3.526) and biopsy method (VAB vs. CNB, p = 0.001, OR = 0.201) was an independent risk factor.

CONCLUSIONS: The PLR may be a predictor of invasion in the postoperative pathology for patients diagnosed with DCIS by preoperative biopsy.}, } @article {pmid32490120, year = {2020}, author = {Fernandez, JM and Collier, EK and Foshee, JP and Davis, T and Hsiao, JL and Shi, VY}, title = {Invasive ductal carcinoma arising from an accessory nipple.}, journal = {JAAD case reports}, volume = {6}, number = {6}, pages = {540-542}, pmid = {32490120}, issn = {2352-5126}, } @article {pmid32488076, year = {2020}, author = {Subudhi, AK and O'Donnell, AJ and Ramaprasad, A and Abkallo, HM and Kaushik, A and Ansari, HR and Abdel-Haleem, AM and Ben Rached, F and Kaneko, O and Culleton, R and Reece, SE and Pain, A}, title = {Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2763}, pmid = {32488076}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans Proteins ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Erythropoiesis/*physiology ; Female ; Gene Expression ; Host-Parasite Interactions/genetics/*physiology ; Humans ; Malaria/*metabolism/parasitology ; Mice ; Mice, Knockout ; Plasmodium chabaudi/genetics/growth & development ; Plasmodium falciparum/genetics/growth & development ; Protozoan Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rodentia ; Secologanin Tryptamine Alkaloids/*metabolism ; Transcriptome ; }, abstract = {Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.}, } @article {pmid32487656, year = {2020}, author = {Fregatti, P and Gipponi, M and Zoppoli, G and Lambertini, M and Blondeaux, E and Belgioia, L and Derosa, R and Murelli, F and Depaoli, F and Ceppi, M and Garlaschi, A and Friedman, D}, title = {Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review.}, journal = {Anticancer research}, volume = {40}, number = {6}, pages = {3543-3550}, doi = {10.21873/anticanres.14343}, pmid = {32487656}, issn = {1791-7530}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*pathology/*surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Mammaplasty/methods ; *Margins of Excision ; Mastectomy/methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Nipples/surgery ; Recurrence ; Tumor Burden ; }, abstract = {BACKGROUND/AIM: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin.

PATIENTS AND METHODS: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR).

RESULTS: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups.

CONCLUSION: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.}, } @article {pmid32483424, year = {2020}, author = {Shin, KS and Laohajaratsang, M and Men, S and Figueroa, B and Dintzis, SM and Fu, D}, title = {Quantitative chemical imaging of breast calcifications in association with neoplastic processes.}, journal = {Theranostics}, volume = {10}, number = {13}, pages = {5865-5878}, pmid = {32483424}, issn = {1838-7640}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM133435/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Breast Diseases/pathology ; Breast Neoplasms/chemistry/*diagnostic imaging/metabolism/pathology ; Calcinosis/*diagnostic imaging/pathology ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Mammography/methods ; Middle Aged ; Sensitivity and Specificity ; Spectrum Analysis, Raman/*methods ; }, abstract = {Calcifications play an essential role in early breast cancer detection and diagnosis. However, information regarding the chemical composition of calcifications identified on mammography and histology is limited. Detailed spectroscopy reveals an association between the chemical composition of calcifications and breast cancer, warranting the development of novel analytical tools to better define calcification types. Previous investigations average calcification composition across broad tissue sections with no spatially resolved information or provide qualitative visualization, which prevents a robust linking of specific spatially resolved changes in calcification chemistry with the pathologic process. Method: To visualize breast calcification chemical composition at high spatial resolution, we apply hyperspectral stimulated Raman scattering (SRS) microscopy to study breast calcifications associated with a spectrum of breast changes ranging from benign to neoplastic processes, including atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. The carbonate content of individual breast calcifications is quantified using a simple ratiometric analysis. Results: Our findings reveal that intra-sample calcification carbonate content is closely associated with local pathological processes. Single calcification analysis supports previous studies demonstrating decreasing average carbonate level with increasing malignant potential. Sensitivity and specificity reach >85% when carbonate content level is used as the single differentiator in separating benign from neoplastic processes. However, the average carbonate content is limiting when trying to separate specific diagnostic categories, such as fibroadenoma and invasive ductal carcinoma. Second harmonic generation (SHG) data can provide critical information to bridge this gap. Conclusion: SRS, combined with SHG, can be a valuable tool in better understanding calcifications in carcinogenesis, diagnosis, and possible prognosis. This study not only reveals previously unknown large variations of breast microcalcifications in association with local malignancy but also corroborates the clinical value of linking microcalcification chemistry to breast malignancy. More importantly, it represents an important step in the development of a label-free imaging strategy for breast cancer diagnosis with tremendous potential to address major challenges in diagnostic discordance in pathology.}, } @article {pmid32480118, year = {2020}, author = {Chan, SJ and Ein-Dor, T and Mayopoulos, PA and Mesa, MM and Sunda, RM and McCarthy, BF and Kaimal, AJ and Dekel, S}, title = {Risk factors for developing posttraumatic stress disorder following childbirth.}, journal = {Psychiatry research}, volume = {290}, number = {}, pages = {113090}, doi = {10.1016/j.psychres.2020.113090}, pmid = {32480118}, issn = {1872-7123}, mesh = {Adult ; Delivery, Obstetric/*psychology/statistics & numerical data ; Female ; Humans ; Labor, Obstetric/*psychology ; Mental Health ; Parturition/*psychology ; Postpartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Pregnancy Outcome/epidemiology/psychology ; Prevalence ; Risk Factors ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; }, abstract = {Women can develop childbirth-related posttraumatic stress disorder (CB-PTSD) in at-term delivery with healthy baby outcome as well as following pre-term delivery and neonatal complications, a potential added stressor. No study compares risk factors of CB-PTSD associated with different infant outcomes. We investigated CB-PTSD risk factors by comparing women with or without neonatal complications. Analysis reveals the importance of antepartum and birth-related risk factors in CB-PTSD above and beyond child outcomes, suggesting childbirth is an independent stressor capable of evoking CB-PTSD.}, } @article {pmid32473405, year = {2020}, author = {Kaltenecker, D and Spirk, K and Ruge, F and Grebien, F and Herling, M and Rupprecht, A and Kenner, L and Pohl, EE and Mueller, KM and Moriggl, R}, title = {STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue.}, journal = {Molecular metabolism}, volume = {40}, number = {}, pages = {101026}, pmid = {32473405}, issn = {2212-8778}, support = {636855/ERC_/European Research Council/International ; I 4157/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adipocytes/metabolism ; Adipose Tissue, Brown/*metabolism ; Adipose Tissue, White/metabolism ; Animals ; Cold-Shock Response/physiology ; Energy Metabolism ; Female ; Lipid Metabolism/physiology ; Lipids/physiology ; Lipolysis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; Obesity/metabolism ; Receptors, Adrenergic, beta/metabolism/physiology ; STAT5 Transcription Factor/*metabolism/physiology ; Thermogenesis/*physiology ; }, abstract = {OBJECTIVE: Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. It is therefore essential to understand the molecular mechanisms that control BAT functions. Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated as being relevant for BAT physiology. However, whether the STAT family member STAT5 is important for the thermogenic property of adipose tissues is unknown. Therefore, we have investigated the role of STAT5 in thermogenic fat in this paper.

METHODS: We performed metabolic and molecular analyses using mice that harbor an adipocyte-specific deletion of Stat5a/b alleles.

RESULTS: We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following β3-adrenergic stimulation. Moreover, mitochondrial respiration of primary differentiated brown adipocytes lacking STAT5 was diminished. Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. Additionally, brown remodeling of white adipose tissue was diminished following chronic β3-adrenergic stimulation, which was accompanied by a decrease in mitochondrial performance.

CONCLUSION: We conclude that STAT5 is essential for the functionality and the β-adrenergic responsiveness of thermogenic adipose tissue.}, } @article {pmid32471471, year = {2020}, author = {Feng, M and Deng, Y and Yang, L and Jing, Q and Zhang, Z and Xu, L and Wei, X and Zhou, Y and Wu, D and Xiang, F and Wang, Y and Bao, J and Bu, H}, title = {Automated quantitative analysis of Ki-67 staining and HE images recognition and registration based on whole tissue sections in breast carcinoma.}, journal = {Diagnostic pathology}, volume = {15}, number = {1}, pages = {65}, pmid = {32471471}, issn = {1746-1596}, support = {2017YFC0113908//National Key Research and Development Program/ ; 2017-CY02-00026-GX//Technological Innovation Project of Chengdu New Industrial Technology Research Institute/ ; ZYGD18012//135 project for disciplines of excellence, West China Hospital/ ; }, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Deep Learning ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Ki-67 Antigen/*analysis ; Sensitivity and Specificity ; *Software ; Staining and Labeling ; }, abstract = {BACKGROUND: The scoring of Ki-67 is highly relevant for the diagnosis, classification, prognosis, and treatment in breast invasive ductal carcinoma (IDC). Traditional scoring method of Ki-67 staining followed by manual counting, is time-consumption and inter-/intra observer variability, which may limit its clinical value. Although more and more algorithms and individual platforms have been developed for the assessment of Ki-67 stained images to improve its accuracy level, most of them lack of accurate registration of immunohistochemical (IHC) images and their matched hematoxylin-eosin (HE) images, or did not accurately labelled each positive and negative cell with Ki-67 staining based on whole tissue sections (WTS). In view of this, we introduce an accurate image registration method and an automatic identification and counting software of Ki-67 based on WTS by deep learning.

METHODS: We marked 1017 breast IDC whole slide imaging (WSI), established a research workflow based on the (i) identification of IDC area, (ii) registration of HE and IHC slides from the same anatomical region, and (iii) counting of positive Ki-67 staining.

RESULTS: The accuracy, sensitivity, and specificity levels of identifying breast IDC regions were 89.44, 85.05, and 95.23%, respectively, and the contiguous HE and Ki-67 stained slides perfectly registered. We counted and labelled each cell of 10 Ki-67 slides as standard for testing on WTS, the accuracy by automatic calculation of Ki-67 positive rate in attained IDC was 90.2%. In the human-machine competition of Ki-67 scoring, the average time of 1 slide was 2.3 min with 1 GPU by using this software, and the accuracy was 99.4%, which was over 90% of the results provided by participating doctors.

CONCLUSIONS: Our study demonstrates the enormous potential of automated quantitative analysis of Ki-67 staining and HE images recognition and registration based on WTS, and the automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy. We will provide those labelled images as an open-free platform for researchers to assess the performance of computer algorithms for automated Ki-67 scoring on IHC stained slides.}, } @article {pmid32468762, year = {2020}, author = {Khattak, MS and Ahmad, F and , }, title = {Role Of Fine Needle Aspiration Cytology In Diagnosis Of Palpable Breast Lesions And Their Comparison With Histopathology.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {32}, number = {1}, pages = {83-86}, pmid = {32468762}, issn = {1819-2718}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*statistics & numerical data ; Breast/*pathology ; *Breast Neoplasms/diagnosis/pathology ; Cross-Sectional Studies ; Female ; Histological Techniques/*statistics & numerical data ; Humans ; Middle Aged ; Pakistan ; Predictive Value of Tests ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to compare the diagnostic utility of fine needle aspiration cytology (FNAC) in breast lesion with gold standard of histopathological diagnosis.

METHODS: This descriptive cross-sectional study was conducted in Pathology department of Bannu Medical College in collaboration with Surgery Department of Khalifa Gul Nawaz Teaching Hospital Bannu as well as other private surgical hospitals of the territory. A total of 88 FNAC of palpable breast lesions were performed and compared with their corresponding histopathological reports. Patients age, location of lesion in breast, and other necessary findings were recorded on predesigned proforma, FNAC performed by using 10 ml syringes. Slides prepared and processed for cytological staining and reported by cytopathologist. Corresponding biopsies were processed for histopathological examination and diagnosis. All female patients of any age with breast lesions were included, and those breast lesions for which no histopathological report was available were excluded. Statistical Package for Social Sciences (SPSS) version 20 was used for calculation of frequencies with percentages and mean with standard deviation. Also, specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value were calculated by using formulas.

RESULTS: In this study the mean age was 34.44±21.57 years and age range was from 16 to 80 years. The most common age group was 26-35 years followed by 36-45 years. In this study sensitivity was (83.33%), specificity was (100 %), positive predictive value was (100 %), negative predictive value was (99.27%) and diagnostic accuracy was 99.30%.

CONCLUSIONS: FNAC breast is an easily approachable, less invasive, cheap, rapid and almost accurate diagnostic tool in the diagnosis of palpable as well as non palpable breast lesions.}, } @article {pmid32467665, year = {2020}, author = {Zhang, X and Xing, C and Guan, W and Chen, L and Guo, K and Yu, A and Xie, K}, title = {Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: a systematic review and meta-analysis.}, journal = {Cancer cell international}, volume = {20}, number = {}, pages = {169}, pmid = {32467665}, issn = {1475-2867}, abstract = {BACKGROUND: Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Therefore, we performed this meta-analysis to elucidate the prognostic and clinicopathological association of nestin expression with breast cancer.

METHODS: A comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.

RESULTS: A total of 15 studies with 6066 breast cancer patients were included in this meta-analysis. Pooled results indicated that positive expression of nestin was significantly associated with reduced breast cancer-specific survival (BCSS, univariate analysis, HR = 2.11, 95% CI [1.79, 2.49], P < 0.00001; multivariate analysis, HR = 1.30, 95% CI [1.06, 1.60], P = 0.01), worse overall survival (OS, univariate analysis, HR = 1.88, 95% CI [1.31, 2.71], P = 0.0007; multivariate analysis, HR = 1.89, 95% CI [1.34, 2.67], P = 0.0003) and poorer recurrence-free survival (univariate analysis, HR = 2.60, 95% CI [1.52, 4.46], P = 0.0005), but not with distant metastasis-free survival in univariate analysis (P > 0.05). In addition, increased nestin expression was correlated with younger age, higher tumor grade, larger tumor size, positive blood vessel invasion and high vascular proliferation index, but not with lymph node metastasis or lymph vessel invasion. Nestin was preferentially expressed in invasive ductal carcinoma, triple-negative breast cancer and basal-like subtypes. Nestin expression was inversely associated with the expression of ER and PR, but not with HER-2. Conversely, nestin expression was positively correlated with the expression of basal-like markers CK5, P-cadherin and EGFR. Moreover, nestin expression was strongly associated with the presence of five basal-like profiles (BLP1-5).

CONCLUSIONS: This meta-analysis revealed the prognostic value and clinicopathological significance of nestin expression in breast cancer. Nestin is an independent prognostic factor for worse BCSS and OS of breast cancer patients. Nestin is also a valuable biomarker for unfavorable clinicopathological features and tumor angiogenesis of breast cancer. Therefore, nestin is a promising therapeutic target for malignant breast cancer, especially for TNBC and basal-like phenotype.}, } @article {pmid32467291, year = {2020}, author = {Shan, NL and Minden, A and Furmanski, P and Bak, MJ and Cai, L and Wernyj, R and Sargsyan, D and Cheng, D and Wu, R and Kuo, HD and Li, SN and Fang, M and Maehr, H and Kong, AN and Suh, N}, title = {Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal Carcinoma In Situ by Vitamin D Compounds.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {13}, number = {8}, pages = {673-686}, pmid = {32467291}, issn = {1940-6215}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AT007036/AT/NCCIH NIH HHS/United States ; R01 AT009152/AT/NCCIH NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology/*prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; DNA Methylation/drug effects ; Datasets as Topic ; Disease Progression ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness/pathology/prevention & control ; Neoplastic Stem Cells/*drug effects/pathology ; RNA-Seq ; Signal Transduction/drug effects/genetics ; Up-Regulation/drug effects ; Vitamin D/*administration & dosage/analogs & derivatives ; }, abstract = {Ductal carcinoma in situ (DCIS), which accounts for one out of every five new breast cancer diagnoses, will progress to potentially lethal invasive ductal carcinoma (IDC) in about 50% of cases. Vitamin D compounds have been shown to inhibit progression to IDC in the MCF10DCIS model. This inhibition appears to involve a reduction in the cancer stem cell-like population in MCF10DCIS tumors. To identify genes that are involved in the vitamin D effects, a global transcriptomic analysis was undertaken of MCF10DCIS cells grown in mammosphere cultures, in which cancer stem-like cells grow preferentially and produce colonies by self-renewal and maturation, in the presence and absence of 1α25(OH)2D3 and a vitamin D analog, BXL0124. Using next-generation RNA-sequencing, we found that vitamin D compounds downregulated genes involved in maintenance of breast cancer stem-like cells (e.g., GDF15), epithelial-mesenchymal transition, invasion, and metastasis (e.g., LCN2 and S100A4), and chemoresistance (e.g., NGFR, PPP1R1B, and AGR2), while upregulating genes associated with a basal-like phenotype (e.g., KRT6A and KRT5) and negative regulators of breast tumorigenesis (e.g., EMP1). Gene methylation status was analyzed to determine whether the changes in expression induced by vitamin D compounds occurred via this mechanism. Ingenuity pathway analysis was performed to identify upstream regulators and downstream signaling pathway genes differentially regulated by vitamin D, including TP63 and vitamin D receptor -mediated canonical pathways in particular. This study provides a global profiling of changes in the gene signature of DCIS regulated by vitamin D compounds and possible targets for chemoprevention of DCIS progression to IDC in patients.}, } @article {pmid32466799, year = {2020}, author = {Onishi, N and Sadinski, M and Hughes, MC and Ko, ES and Gibbs, P and Gallagher, KM and Fung, MM and Hunt, TJ and Martinez, DF and Shukla-Dave, A and Morris, EA and Sutton, EJ}, title = {Ultrafast dynamic contrast-enhanced breast MRI may generate prognostic imaging markers of breast cancer.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {58}, pmid = {32466799}, issn = {1465-542X}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology/therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/therapy ; Carcinoma, Lobular/diagnostic imaging/pathology/therapy ; Contrast Media ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics.

METHODS: Consecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4-6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7-4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values < 0.05 were considered statistically significant.

RESULTS: Significantly larger MS and shorter BAT were observed for invasive carcinoma than ductal carcinoma in situ (DCIS) (P < 0.001 and P = 0.008, respectively). Significantly shorter BAT was observed for invasive carcinomas with more aggressive characteristics than those with less aggressive characteristics: grade 3 vs. grades 1-2 (P = 0.025), invasive ductal carcinoma vs. invasive lobular carcinoma (P = 0.002), and triple negative or HER2 type vs. luminal type (P < 0.001).

CONCLUSIONS: Ultrafast DCE-MRI-derived parameters showed a strong relationship with some breast cancer characteristics, especially histopathology and molecular subtype.}, } @article {pmid32463003, year = {2020}, author = {Heidl, C and Behrens, J and Jahn, P}, title = {Der Einfluss von Glückserleben und Gesundheitszustand auf die Lebenszufriedenheit im Alter - Eine empirische Längsschnittstudie mit den Daten des Sozio-ökonomischen Panels.}, journal = {Pflege}, volume = {33}, number = {3}, pages = {179-180}, doi = {10.1024/1012-5302/a000734}, pmid = {32463003}, issn = {1012-5302}, } @article {pmid32462260, year = {2020}, author = {Hassan, Z and Boulos, F and Abbas, J and El Charif, MH and Assi, H and Sbaity, E}, title = {Intracystic papillary carcinoma: clinical presentation, patterns of practice, and oncological outcomes.}, journal = {Breast cancer research and treatment}, volume = {182}, number = {2}, pages = {317-323}, doi = {10.1007/s10549-020-05680-9}, pmid = {32462260}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*diagnosis/epidemiology/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology/pathology/therapy ; Carcinoma, Papillary/*diagnosis/epidemiology/pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Mammary Glands, Human/*pathology/surgery ; Mastectomy ; Medical History Taking ; Middle Aged ; Neoplasm Invasiveness/diagnosis/pathology ; Neoplasm Recurrence, Local/epidemiology/pathology/prevention & control ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {BACKGROUND: Intracystic/encapsulated papillary carcinoma remains a poorly understood disease of the breast with a little amount of reports that describe it. It shares features with DCIS and IDC and predominantly affects postmenopausal women. This study aims to evaluate the clinical presentation, treatment, and outcomes in IPC patients managed at our institution.

METHODS: We retrospectively pooled twenty-eight IPC patients' medical records at our institution. Descriptive analysis of clinicopathological characteristics, approach, and outcomes was done along with a quantitative statistical analysis.

RESULTS: Cases were divided into three groups: isolated IPC, IPC associated with DCIS, and IPC associated with Invasive Carcinoma. Treatment modalities varied according to the IPC type and its associated components. All patients presented with a palpable mass. Immunohistochemical staining revealed that all isolated IPCs were ER and PR positive and HER2 negative. Lymph node dissection proved necessary only in IPC associated invasive carcinoma. Irregular borders and lobulations, among others, were found on non-invasive core biopsies that turned out to be associated with invasion on surgical pathology. All patients were alive after a median follow-up time of 23 months when the study was over with no reports of recurrence.

CONCLUSION: IPC cases and treatment approaches at our institution appear similar to the available literature and confirm the excellent prognosis among IPC. Even more, further studies into the key features such as BMI, family history, and radiological findings are necessary for a potential algorithm that could assess for risk of finding invasion in surgical pathology and subsequently the need for axillary/sentinel lymph node biopsy.}, } @article {pmid32457515, year = {2020}, author = {Goodes, LM and King, GK and Goodwin, DM and Watts, A and Bardsley, J and Middleton, J and Bragge, P and Dunlop, SA}, title = {Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.}, journal = {Spinal cord}, volume = {58}, number = {12}, pages = {1291-1300}, pmid = {32457515}, issn = {1476-5624}, mesh = {Humans ; Inpatients ; Longitudinal Studies ; *Spinal Cord Injuries/therapy ; *Urinary Bladder, Neurogenic/etiology/therapy ; }, abstract = {STUDY DESIGN: Qualitative survey.

OBJECTIVES: Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.

SETTING: Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).

METHODS: Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.

RESULTS: Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6 hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.

CONCLUSIONS: Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.}, } @article {pmid32456482, year = {2020}, author = {Grypari, IM and Logotheti, S and Lazaris, AC and Kallidonis, P and Fokaefs, E and Melachrinou, M and Zolota, V and Tzelepi, V}, title = {Isolated Intraductal Carcinoma of the Prostate in Prostatectomy Specimens: Report of 2 Cases and Review of the Literature.}, journal = {International journal of surgical pathology}, volume = {28}, number = {8}, pages = {918-924}, doi = {10.1177/1066896920920357}, pmid = {32456482}, issn = {1940-2465}, mesh = {Aged, 80 and over ; Biopsy, Large-Core Needle ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology/surgery ; Humans ; Male ; Middle Aged ; Prostate/*pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {Intraductal carcinoma of the prostate (IDCp) is a distinct neoplastic entity, and although recognized for some time, it was included for the first time in the histologic classification of prostate cancer in the 2016 publication of World Health Organization. IDCp represents an intraductal or intra-acinar proliferation of malignant cells, with preservation of the basal cell layer. Even though IDCp is usually accompanied by a high-grade invasive component, low-grade invasive carcinoma can rarely be seen adjacent to the lesion. Even rarer is the incidence of isolated IDCp in needle biopsies, while a few such cases have been reported in prostatectomy specimens. We report 2 cases with isolated IDCp without any invasive component. A review of the literature is performed including the diagnostic challenges of IDCp and its morphologic mimics, immunohistochemical markers, molecular aspects, and prognostic implications. Even though it is not yet clear whether IDCp represents an intraductal spread of invasive cancer or a precursor of invasive carcinoma, the existence of isolated IDCp reinforces the idea that, at least in some of the cases, IDCp is a precancerous lesion. Further molecular studies need to be performed in order to clarify its pathogenesis.}, } @article {pmid32449173, year = {2020}, author = {Watanuki, R and Hayashida, T and Yokoe, T and Kawai, Y and Kikuchi, M and Nakashoji, A and Nagayama, A and Seki, T and Takahashi, M and Kitagawa, Y}, title = {Impact of neoadjuvant and adjuvant chemotherapy on invasive lobular carcinoma: A propensity score-matched analysis of SEER data.}, journal = {The breast journal}, volume = {26}, number = {9}, pages = {1765-1770}, doi = {10.1111/tbj.13884}, pmid = {32449173}, issn = {1524-4741}, mesh = {*Breast Neoplasms/drug therapy/surgery ; *Carcinoma, Ductal, Breast/drug therapy ; *Carcinoma, Lobular/drug therapy/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Neoadjuvant Therapy ; Propensity Score ; Retrospective Studies ; }, abstract = {Invasive lobular carcinoma (ILC) has a different treatment response from invasive ductal carcinoma (IDC). We assessed whether perioperative chemotherapy was associated with improved prognosis in patients with ILC. Retrospective data of women who underwent surgery for ILC were extracted from the SEER database. Subjects were divided into non-chemotherapy and chemotherapy groups. Overall, 10 537 patients were included, and 2107 patients were stratified into each group after propensity score matching. Perioperative chemotherapy significantly improved 10-year survival rates for ILC, particularly in patients with large tumor size and lymph node metastases. Perioperative chemotherapy is effective for ILC patients with proper selection.}, } @article {pmid32449101, year = {2020}, author = {Baran, M and Ozturk, F and Canoz, O and Onder, GO and Yay, A}, title = {The effects of apoptosis and apelin on lymph node metastasis in invasive breast carcinomas.}, journal = {Clinical and experimental medicine}, volume = {20}, number = {4}, pages = {507-514}, doi = {10.1007/s10238-020-00635-2}, pmid = {32449101}, issn = {1591-9528}, support = {TSA-7545//Departamento de Investigaciones Científicas y Tecnológicas, Universidad de Santiago de Chile (CL)/ ; }, mesh = {Age Factors ; Apelin/*metabolism ; Apoptosis/physiology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis/*pathology ; Middle Aged ; }, abstract = {This study aimed to evaluate the biological and clinical significance of apelin-36 in breast cancer and to compare apelin-36 expression and apoptotic index in both breast tissue and metastatic lymph nodes in patients with invasive breast carcinoma. In this study, both tumor tissue and metastatic lymph nodes of the same patient were collected from 60 cases of invasive breast carcinoma patients (IDC, ILC) and 20 cases of normal breast tissue with no tumor from mammoplasty were used as the control group. The expression of apelin was examined with immunohistochemically, and the apoptotic index was examined with TUNEL methods. According to Kruskal-Wallis analysis, there was a significant difference between IDC and the control group when the apelin expression was compared between the breast tissues (p = 0.001). There were significant differences between the three groups when comparing relationships with apoptotic index (p < 0.001). According to the Mann-Whitney U test, both tumor size and expression of apelin in lymph nodes in ILCs were significantly higher than IDCs. (p = 0.026, p = 0.024, respectively). According to correlation analysis, there was a good correlation between the expression of apelin in breast tissue and apelin expression in lymph nodes (p = 0.000). It is also found a similar relationship in terms of the apoptotic index (p = 0.000). In addition, the negative correlation was found between apelin expression and the apoptotic index in breast tissues (p = 0.003). Based on these results, apelin-36 can be used as a marker for determining the metastasis potential in invasive breast cancer.}, } @article {pmid32448217, year = {2020}, author = {Liu, H and Zhan, H and Sun, D}, title = {Comparison of [99m]Tc-MIBI scintigraphy, ultrasound, and mammography for the diagnosis of BI-RADS 4 category lesions.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {463}, pmid = {32448217}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/diagnostic imaging/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/metabolism ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Prognosis ; ROC Curve ; Radionuclide Imaging/*methods ; Radiopharmaceuticals/metabolism ; Retrospective Studies ; Technetium Tc 99m Sestamibi/*metabolism ; Ultrasonography, Mammary/*methods ; Young Adult ; }, abstract = {BACKGROUND: We sought to determine the diagnostic efficacy of Breast-specific gamma imaging (BSGI) in Chinese women with BI-RADS 4 category lesions and to compare this efficacy to that of ultrasound/mammography.

METHODS: We retrospectively analyzed data from 177 women that had undergone BSGI of BI-RADS 4 category lesions originally detected via ultrasound and/or mammography.

RESULTS: Of these 177 cases, 117 (66.1%) were malignant lesions and 60 (33.9%) were benign. The sensitivity, specificity, positive predictive values, and negative predictive values of BSGI were 94.9% (111/117), 78.3% (47/60), 89.5% (111/124), and 88.7% (47/53), respectively. The specificity and positive predictive values for mammography were 48.3% (29/60) and 77.5% (107/138), while for ultrasound they were 53.3% (32/60) and 79.6% (109/137), respectively. The sensitivity and specificity of BSGI for the detection of lesions ≤1 cm in size were 90.9% (10/11) and 88.0% (22/25), respectively, while for breast lesions >1 cm in size these values were 94.3% (100/106) and 71.4% (25/35), respectively. In addition, BSGI sensitivity and specificity values for dense breast tissue were 94.0% (79/84) and 78.0% (39/50), respectively, whereas for non-dense breast tissue these vales were 97.0% (32/33) and 80.0% (8/10), respectively. The sensitivity of BSGI for invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) was 98.9% (95/96) and 75.0% (9/12), respectively. The tumor to normal tissue ratio of BSGI for malignant lesions was significantly higher than for benign lesions (2.18 ± 1.17 vs 1.66 ± 0.40, t = 7.56, P<0.05).

CONCLUSIONS: These results indicate that BSGI is highly sensitive for the detection of such lesions, achieving good positive/negative predictive values. This suggests that for IDC in particular, BSGI is superior to ultrasound and mammography for the diagnosis of BI-RADS 4 category lesions, although this was less apparent for the diagnosis of DCIS lesions. BSGI exhibited excellent performance in dense breast tissue and for the detection of lesions ≤1 cm in size.}, } @article {pmid32447596, year = {2020}, author = {Ha, SM and Chang, JM and Lee, SH and Kim, ES and Kim, SY and Cho, N and Moon, WK}, title = {Diffusion-weighted MRI at 3.0 T for detection of occult disease in the contralateral breast in women with newly diagnosed breast cancer.}, journal = {Breast cancer research and treatment}, volume = {182}, number = {2}, pages = {283-297}, doi = {10.1007/s10549-020-05697-0}, pmid = {32447596}, issn = {1573-7217}, support = {HI15C1532//Korea Health Industry Development Institute/Republic of Korea ; HA17C0056//Ministry of Health and Welfare/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asymptomatic Diseases ; Biopsy ; Breast/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Contrast Media/administration & dosage ; Cost-Benefit Analysis ; Diffusion Magnetic Resonance Imaging/economics/*methods ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Software ; }, abstract = {PURPOSE: Diffusion-weighted magnetic resonance imaging (DW-MRI) offers unenhanced method to detect breast cancer without cost and safety concerns associated with dynamic contrast-enhanced (DCE) MRI. Our purpose was to evaluate the performance of DW-MRI at 3.0T in detection of clinically and mammographically occult contralateral breast cancer in patients with unilateral breast cancer.

METHODS: Between 2017 and 2018, 1130 patients (mean age 53.3 years; range 26-84 years) with newly diagnosed unilateral breast cancer who underwent breast MRI and had no abnormalities on clinical and mammographic examinations of contralateral breast were included. Three experienced radiologists independently reviewed DW-MRI (b = 0 and 1000 s/mm[2]) and DCE-MRI and assigned a BI-RADS category. Using histopathology or 1-year clinical follow-up, performance measures of DW-MRI were compared with DCE-MRI.

RESULTS: A total of 21 (1.9%, 21/1130) cancers were identified (12 ductal carcinoma in situ and 9 invasive ductal carcinoma; mean invasive tumor size, 8.0 mm) in the contralateral breast. Cancer detection rate of DW-MRI was 13-15 with mean of 14 per 1000 examinations (95% confidence interval [CI] 9-23 per 1000 examinations), which was lower than that of DCE-MRI (18-19 with mean of 18 per 1000 examinations, P = 0.01). A lower abnormal interpretation rate (14.0% versus 17.0%, respectively, P < 0.001) with higher specificity (87.3% versus 84.6%, respectively, P < 0.001) but lower sensitivity (77.8% versus 96.8%, respectively, P < 0.001) was noted for DW-MRI compared to DCE-MRI.

CONCLUSIONS: DW-MRI at 3.0T has the potential as a cost-effective tool for evaluation of contralateral breast in women with newly diagnosed breast cancer.}, } @article {pmid32446129, year = {2020}, author = {Nadrljanski, MM and Milosevic, ZC}, title = {Tumor texture parameters of invasive ductal breast carcinoma in neoadjuvant chemotherapy: early identification of non-responders on breast MRI.}, journal = {Clinical imaging}, volume = {65}, number = {}, pages = {119-123}, doi = {10.1016/j.clinimag.2020.04.016}, pmid = {32446129}, issn = {1873-4499}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; *Neoadjuvant Therapy ; Radiography ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: Texture analysis (TA) parameters (variance of SI, mean of gradient, variance of gradient, kurtosis of SI, and entropy) in patients with invasive ductal carcinoma (IDC) contribute to objective assessment of neoadjuvant chemotherapy (NACT) activity. The objective was to assess TA parameters in early identification of non-responders (NR) in NACT, after the 2nd cycle of NACT.

MATERIAL AND METHODS: Fifty patients (N = 50) were included in the retrospective analysis of baseline and MRI following the 2nd cycle of NACT. TA parameters were computed and correlated to the lesion size and DWI-ADC in NR (N1 = 25). Additional matched responders (R, N2 = 25) assessed for the same parameters, served as the control group.

RESULTS: Tumor size and ADC did not change significantly in NR after the 2nd cycle of NACT (2.88 ± 0.38 vs. 2.76 ± 0.36 [cm], p = 0.131; 1.01 ± 0.14 vs. 1.05 ± 0.13 [mm[2]/s × 10[-3]], p = 0.363), but TA parameters changed significantly: variance of gradient (346.5 ± 12.6 vs. 355.6 ± 16.9, p = 0.01), kurtosis of SI (1.47 ± 0.09 vs. 1.54 ± 0.11, p = 0.02), entropy LH (60.39 ± 4.34 vs. 64.42 ± 3.05, p = 0.001) and entropy HL (61.02 ± 5.51 vs. 65.63 ± 3.63, p < 0.00001). TA parameters, particularly entropy (EN LH 64.42 ± 3.05 vs. 61.59 ± 1.76, p < 0.0001; EN HL 65.63 ± 3.63 vs. 62.89 ± 2.05, p < 0.0001), significantly differ between NR and R in early response assessment.

CONCLUSION: Entropy, kurtosis of SI and variance of gradient tend to increase in NR. TA parameters significantly differ between NR and R after the 2nd cycle of NACT. TA parameters, related to morpho-functional parameters may contribute to early NR identification.}, } @article {pmid32444590, year = {2021}, author = {Choudhury, A and Perumalla, S}, title = {Detecting breast cancer using artificial intelligence: Convolutional neural network.}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {29}, number = {1}, pages = {33-43}, doi = {10.3233/THC-202226}, pmid = {32444590}, issn = {1878-7401}, mesh = {Algorithms ; *Artificial Intelligence ; *Breast Neoplasms/diagnosis ; Diagnosis, Computer-Assisted ; Humans ; Neural Networks, Computer ; }, abstract = {BACKGROUND: One of the most broadly founded approaches to envisage cancer treatment relies upon a pathologist's efficiency to visually inspect the appearances of bio-markers on the invasive tumor tissue section. Lately, deep learning techniques have radically enriched the ability of computers to identify objects in images fostering the prospect for fully automated computer-aided diagnosis. Given the noticeable role of nuclear structure in cancer detection, AI's pattern recognizing ability can expedite the diagnostic process.

OBJECTIVE: In this study, we propose and implement an image classification technique to identify breast cancer.

METHODS: We implement the convolutional neural network (CNN) on breast cancer image data set to identify invasive ductal carcinoma (IDC).

RESULT: The proposed CNN model after data augmentation yielded 78.4% classification accuracy. 16% of IDC (-) were predicted incorrectly (false negative) whereas 25% of IDC (+) were predicted incorrectly (false positive).

CONCLUSION: The results achieved by the proposed approach have shown that it is feasible to employ a convolutional neural network particularly for breast cancer classification tasks. However, a common problem in any artificial intelligence algorithm is its dependence on the data set. Therefore, the performance of the proposed model might not be generalized.}, } @article {pmid32444289, year = {2020}, author = {Seebacher, F and Zeigerer, A and Kory, N and Krahmer, N}, title = {Hepatic lipid droplet homeostasis and fatty liver disease.}, journal = {Seminars in cell & developmental biology}, volume = {108}, number = {}, pages = {72-81}, doi = {10.1016/j.semcdb.2020.04.011}, pmid = {32444289}, issn = {1096-3634}, mesh = {Animals ; Fatty Liver/*metabolism/therapy ; *Homeostasis ; Humans ; Lipid Droplets/*metabolism ; Lipid Metabolism ; Liver/*metabolism ; }, abstract = {In cells, lipids are stored in lipid droplets, dynamic organelles that adapt their size, abundance, lipid and protein composition and organelle interactions to metabolic changes. Lipid droplet accumulation in the liver is the hallmark of non-alcoholic fatty liver disease (NAFLD). Due to the prevalence of obesity, the strongest risk factor for steatosis, NAFLD and its associated complications are currently affecting more than 1 billion people worldwide. Here, we review how triglyceride and phospholipid homeostasis are regulated in hepatocytes and how imbalances between lipid storage, degradation and lipoprotein secretion lead to NAFLD. We discuss how organelle interactions are altered in NAFLD and provide insights how NAFLD progression is associated with changes in hepatocellular signaling and organ-crosstalk. Finally, we highlight unsolved questions in hepatic LD and lipoprotein biology and give an outlook on therapeutic options counteracting hepatic lipid accumulation.}, } @article {pmid32439746, year = {2020}, author = {Bacorn, C and Kim, E and Borowsky, AD and Lin, LK}, title = {Previously undiagnosed neuroendocrine tumour mimicking breast cancer metastasis to the orbit.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, pmid = {32439746}, issn = {1757-790X}, mesh = {Adenocarcinoma/*pathology/therapy ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*secondary/therapy ; Diplopia ; Female ; Humans ; Intestinal Neoplasms/*pathology/therapy ; Neuroendocrine Tumors/*pathology/therapy ; Octreotide/therapeutic use ; Orbit ; Orbital Neoplasms/*secondary/therapy ; Pancreatic Neoplasms/*pathology/therapy ; Stomach Neoplasms/*pathology/therapy ; }, abstract = {Metastatic neuroendocrine neoplasms to the breast are rare and histopathologic overlap with mammary carcinomas has led to misdiagnosis. We present a case of a middle-aged woman with diplopia and a right medial rectus mass. Metastatic breast cancer was initially suspected based on a history of invasive ductal carcinoma. Detailed immunohistochemistry of the orbital biopsy, gallium-68 dotatate positron emission tomography-CT, and reevaluation of her prior breast specimen, demonstrated that her initial breast carcinoma diagnosis was in error and she was ultimately diagnosed with a previously unknown gastrointestinal neuroendocrine tumour metastatic to both the orbit and breast. This case highlights the challenges of differentiating between metastatic neuroendocrine tumours and invasive mammary carcinomas with neuroendocrine differentiation both in the breast and in the orbit. It is important to recognise the overlap so that a primary neuroendocrine neoplasm is not missed, or treatment significantly delayed.}, } @article {pmid32438745, year = {2020}, author = {Moran Lauter, AN and Rutter, L and Cook, D and O'Rourke, JA and Graham, MA}, title = {Examining Short-Term Responses to a Long-Term Problem: RNA-Seq Analyses of Iron Deficiency Chlorosis Tolerant Soybean.}, journal = {International journal of molecular sciences}, volume = {21}, number = {10}, pages = {}, pmid = {32438745}, issn = {1422-0067}, support = {Project 5030-21220-006-00D//Agricultural Research Service/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; *Iron Deficiencies ; Plant Leaves/genetics ; Plant Necrosis and Chlorosis/*genetics ; Plant Roots/genetics ; *RNA-Seq ; Signal Transduction ; Soybeans/*genetics ; Stress, Physiological/genetics ; Transcription Factors/metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) is a global crop production problem, significantly impacting yield. However, most IDC studies have focused on model species, not agronomically important crops. Soybean is the second largest crop grown in the United States, yet the calcareous soils across most of the upper U.S. Midwest limit soybean growth and profitability. To understand early soybean iron stress responses, we conducted whole genome expression analyses (RNA-sequencing) of leaf and root tissue from the iron efficient soybean (Glycine max) cultivar Clark, at 30, 60 and 120 min after transfer to iron stress conditions. We identified over 10,000 differentially expressed genes (DEGs), with the number of DEGs increasing over time in leaves, but decreasing over time in roots. To investigate these responses, we clustered our expression data across time to identify suites of genes, their biological functions, and the transcription factors (TFs) that regulate their expression. These analyses reveal the hallmarks of the soybean iron stress response (iron uptake and homeostasis, defense, and DNA replication and methylation) can be detected within 30 min. Furthermore, they suggest root to shoot signaling initiates early iron stress responses representing a novel paradigm for crop stress adaptations.}, } @article {pmid32424149, year = {2020}, author = {Cheung, SM and Husain, E and Masannat, Y and Miller, ID and Wahle, K and Heys, SD and He, J}, title = {Lactate concentration in breast cancer using advanced magnetic resonance spectroscopy.}, journal = {British journal of cancer}, volume = {123}, number = {2}, pages = {261-267}, pmid = {32424149}, issn = {1532-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Female ; Glycolysis/genetics ; Humans ; Lactate Dehydrogenase 5/genetics/metabolism ; Lactic Acid/isolation & purification/*metabolism ; Magnetic Resonance Spectroscopy ; Middle Aged ; *Prognosis ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {BACKGROUND: Precision medicine in breast cancer demands markers sensitive to early treatment response. Aerobic glycolysis (AG) upregulates lactate dehydrogenase A (LDH-A) with elevated lactate production; however, existing approaches for lactate quantification are either invasive or impractical clinically.

METHODS: Thirty female patients (age 39-78 years, 15 grade II and 15 grade III) with invasive ductal carcinoma were enrolled. Lactate concentration was quantified from freshly excised whole tumours with double quantum filtered (DQF) magnetic resonance spectroscopy (MRS), and Nottingham Prognostic Index (NPI), LDH-A and proliferative marker Ki-67 were assessed histologically.

RESULTS: There was a significantly higher lactate concentration (t = 2.2224, p = 0.0349) in grade III (7.7 ± 2.9 mM) than in grade II (5.5 ± 2.4 mM). Lactate concentration was correlated with NPI (ρ = 0.3618, p = 0.0495), but not with Ki-67 (ρ = 0.3041, p = 0.1023) or tumour size (r = 0.1716, p = 0.3645). Lactate concentration was negatively correlated with LDH-A (ρ = -0.3734, p = 0.0421).

CONCLUSION: Our results showed that lactate concentration in whole breast tumour from DQF MRS is sensitive to tumour grades and patient prognosis.}, } @article {pmid32423952, year = {2020}, author = {Bork, JT and Claeys, KC and Heil, EL and Banoub, M and Leekha, S and Sorkin, JD and Kleinberg, M}, title = {A Propensity Score Matched Study of the Positive Impact of Infectious Diseases Consultation on Antimicrobial Appropriateness in Hospitalized Patients with Antimicrobial Stewardship Oversight.}, journal = {Antimicrobial agents and chemotherapy}, volume = {64}, number = {8}, pages = {}, pmid = {32423952}, issn = {1098-6596}, support = {P30 AG028747/AG/NIA NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; *Communicable Diseases/drug therapy ; Cross-Sectional Studies ; Humans ; Propensity Score ; Referral and Consultation ; }, abstract = {Hospital-based antibiotic stewardship (AS) programs provide oversight and guidance for appropriate antimicrobial use in acute care settings. Infectious disease expertise is beneficial in the care of hospitalized patients with infections. The impact of infectious diseases consultation (IDC) on antimicrobial appropriateness in a large tertiary hospital with an established AS program was investigated. This was a cross-sectional study from October 2017 to March 2019 at a large academic hospital with an AS-directed prospective audit and feedback process and multiple IDC services. Antimicrobial appropriateness was adjudicated by an AS team member after antimicrobial start. Antimicrobial appropriateness was compared among antimicrobial orders with and without IDC using propensity score matching and multivariable logistic regression. Analyses were stratified by primary services caring for the patients. There were 10,508 antimicrobial orders from 6,165 unique patient encounters. Overall appropriateness was 92%, with higher appropriateness among patients with IDC versus without IDC (94% versus 84%; P < 0.0001). After propensity score matching and adjustment for certain antibiotics, organisms, syndromes, and locations, IDC was associated with a greater antimicrobial appropriateness odds ratio (OR) of 2.4 (95% confidence interval [CI], 1.9 to 3.0). Stratification by primary service showed an OR of 2.9 (95% CI, 2.1 to 3.8) for surgical specialties and an OR of 1.6 (95% CI, 1.1 to 2.2) for medical specialties. Even with a high overall antimicrobial appropriateness, patients with IDC had greater odds of antimicrobial appropriateness than those without IDC, and this impact was greater in surgical specialties. Infectious diseases consultation can be synergistic with antimicrobial stewardship programs.}, } @article {pmid32423910, year = {2020}, author = {O'Connor, P and Bhadbhade, P and Khan, Q and Williamson, S}, title = {Acral vascular syndrome during an immune checkpoint inhibitor.}, journal = {BMJ case reports}, volume = {13}, number = {5}, pages = {}, pmid = {32423910}, issn = {1757-790X}, mesh = {Black or African American ; Diagnosis, Differential ; Female ; Fingers/blood supply/pathology ; Gangrene/chemically induced/*diagnostic imaging/*pathology/surgery ; Humans ; Immune Checkpoint Inhibitors/*adverse effects ; Middle Aged ; Raynaud Disease/chemically induced/*diagnostic imaging/*pathology/surgery ; Thrombosis ; Vasculitis ; }, abstract = {Immune checkpoint inhibitors, including antiprogrammed death cell protein 1 (anti-PD-1) and anti cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), have been associated with a range of autoimmune-related side effects since their introduction in cancer treatment. Small vessel digital necrosis, referred to as the acral vascular syndrome, is a rare but serious complication that can result in loss of digits. Here we present a case report of acral vascular syndrome and review possible aetiologies. A 45- year-old woman with invasive ductal carcinoma of the left breast presented to the emergency department during neoadjuvant treatment with carboplatin, docetaxel and pembrolizumab with complaints of severe pain in her right third digit. She had physical findings consistent with ischaemic necrosis and gangrene of the distal phalanx. Angiography demonstrated Raynaud's phenomenon in the distal portion of the digits. Laboratory testing showed a weakly positive RNA polymerase III antibody level. Her case resulted in surgical amputation of her affected digit after partial resolution of symptoms with prednisone, vasodilators and antibiotics.}, } @article {pmid32420535, year = {2020}, author = {Fernandez, RAS and Lau, RWH and Yu, PSY and Siu, ICH and Chan, JWY and Ng, CSH}, title = {Use of custom made 3-dimensional printed surgical guide for manubrio-sternal resection of solitary breast cancer metastasis: case report.}, journal = {AME case reports}, volume = {4}, number = {}, pages = {12}, pmid = {32420535}, issn = {2523-1995}, abstract = {A 44-year-old lady with solitary 4.4-cm metastasis to the manubrium from a previously resected invasive ductal carcinoma of the left breast underwent manubrio-sternal resection. We describe our unique approach of using 3-dimensional (3D)-computed tomography (CT) image segmentation planning for reconstructing desirable resection boundaries, design of ideal superficial and deep surgical resection guides, and followed by 3D printing of guides using autoclavable thermoplastic for use during surgery. The surgical guides over the ribs and sternum rapidly and accurately define resection lines intraoperatively, achieve good surgical margins, and could reduce resection and reconstruction related morbidity for performing complex surgical resection of the chest wall. The patient was discharged 2 weeks postoperatively and remained free from local recurrence on CT scan 1-year after resection.}, } @article {pmid32420269, year = {2020}, author = {Bi, Z and Chen, P and Song, XR and Wang, YS}, title = {The study of internal mammary lymph node dissection guided by modified radiotracer injection technique in breast cancer-a case report and review.}, journal = {Gland surgery}, volume = {9}, number = {2}, pages = {430-436}, pmid = {32420269}, issn = {2227-684X}, abstract = {In addition to axillary lymph node (ALN), internal mammary lymph node (IMLN) could also provide important prognostic information. In this paper, we will introduce a case of breast cancer patient whose preoperative lymphoscintigraphy revealed that there were "hot-spots" in bilateral intercostal space. The bilateral IMLN found by preoperative lymphoscintigraphy is a rare phenomenon. She received ipsilateral internal mammary sentinel lymph node biopsy (IM-SLNB) and IMLN dissection and contralateral IM-SLNB. She was diagnosed as pT2N3bM1 breast cancer based on the positive IMLN and positive ALN. After performing surgery, the pathology indicated: (left breast) invasive ductal carcinoma (3.0×3.0 cm[2]), ALN (3/30), ipsilateral internal mammary sentinel lymph node (IMSLN) (1/2), IMLN (0/2); contralateral IMSLN (1/1). After performing IMLN surgery, the pathology staging increased from pT2N1aM0 to pT2N3bM1. And the irradiation therapy choice had been changed, she received irradiation therapy include chest wall, supraclavicular region, ipsilateral IMLN and contralateral IMLN. The treatment benefit had been increased. When the ipsilateral internal mammary lymphatic vessels were obstructed, deep lymphatic system might drain from ipsilateral IMLN to contralateral IMLN. The contralateral IMLN metastasis belongs to distant metastasis. The IMLN irradiation therapy should be tailored and balanced based on the statues of IMLN. With effective application of systemic therapy, the localized treatment advantage benefited from IMLN surgery might be transferred to survival benefit.}, } @article {pmid32420252, year = {2020}, author = {Chen, R and Hu, B and Zhang, Y and Liu, C and Zhao, L and Jiang, Y and Xu, Y}, title = {Differential diagnosis of plasma cell mastitis and invasive ductal carcinoma using multiparametric MRI.}, journal = {Gland surgery}, volume = {9}, number = {2}, pages = {278-290}, pmid = {32420252}, issn = {2227-684X}, abstract = {BACKGROUND: Evaluate the potential of multiparametric magnetic resonance imaging (MRI) for the differential diagnosis of plasma cell mastitis (PCM) and invasive ductal carcinoma (IDC).

METHODS: A total of 465 female patients, including 197 PCM (42.4%) and 268 IDC (57.6%), were examined using breast MRI scanning using routine sequences, dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). The MRI features of PCM and IDC lesions were analyzed and compared to the histological results.

RESULTS: Compared to IDC, the PCM lesions were more frequent in the subareolar regions, hyperintense on T2WI (P<0.01) and showed an initial signal increase ≤90%, a persistent and plateau pattern of time-intensity curves, non-mass enhancement, multiple rim enhancements, central hyperintensity on DWI, a higher ADC value, and total choline (tCho) peak negative and tCho peak integral <29.95 AU (P<0.01). The following breast-associated findings were also observed frequently in PCM: Ipsilateral breast enlargement, nipple retraction, skin thickening, peripheral edema and axillary lymphadenopathy. However, no significant difference was observed between the two groups for the shape, border and adjacent vessel signs of the lesion.

CONCLUSIONS: Some of the MRI features of PCM and IDC lesions were different. An integrated analysis of these multiparametric MRI features can thus assist in the differential diagnosis of PCM and IDC lesions.}, } @article {pmid32420072, year = {2020}, author = {Hu, Z and Zou, X and Qin, S and Li, Y and Wang, H and Yu, H and Sun, S and Wu, X and Wang, J and Chang, J}, title = {Hormone receptor expression correlates with EGFR gene mutation in lung cancer in patients with simultaneous primary breast cancer.}, journal = {Translational lung cancer research}, volume = {9}, number = {2}, pages = {325-336}, pmid = {32420072}, issn = {2218-6751}, abstract = {BACKGROUND: The coexistence of double primaries of lung cancer (LC) and breast cancer (BC) are not uncommon in women, but there has been limited research conducted of their molecular association. To decipher the internal pathogenesis of LC in patients with concurrent BC and LC, this study explored the clinical factors and relationship between hormone receptor (HR) expression and epidermal growth factor receptor (EGFR) gene mutation.

METHODS: The clinicopathological characteristics of 400 female patients clinically diagnosed with double primary LC and BC at Fudan University Shanghai Cancer Center were collected. Pathological discrimination was performed to further confirm the double primaries in patients with available tissues. LC samples were then examined to detect EGFR gene mutation status by PCR-based assays and HR expression by immunohistochemistry (IHC). As a control cohort, the characteristics of 114 consecutive patients with LC only were compared with the double-primary patient group.

RESULTS: A total of 169 patients were pathologically confirmed with simultaneous LC and BC between January 2010 and October 2018. The dominant LC subtype was adenocarcinoma (ADC) (95.1%), and invasive ductal carcinoma (IDC) was the main BC subtype (71.0%). Synchronous and metachronous double primary BC-LC cases accounted for 39.1% and 60.9% of the patients, respectively. The absence of family cancer history was associated with a shorter interval between the two primary cancer diagnoses. Among 64 patients with EGFR mutations, 34.4% had HR-positive LC tissue, compared with 0/24 (0%) of those with EGFR wild-type LC (P<0.001). All of the patients with positive HR expression harbored an activating EGFR mutation (n=22); however, no correlation was observed in the control cohort.

CONCLUSIONS: Double primary BC-LC patients have distinctive clinicopathological features compared to those with LC only. The expression of HRs is significantly correlated with EGFR mutation status of LC tissues.}, } @article {pmid32416533, year = {2020}, author = {Syed, AP and Greulich, F and Ansari, SA and Uhlenhaut, NH}, title = {Anti-inflammatory glucocorticoid action: genomic insights and emerging concepts.}, journal = {Current opinion in pharmacology}, volume = {53}, number = {}, pages = {35-44}, doi = {10.1016/j.coph.2020.03.003}, pmid = {32416533}, issn = {1471-4973}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Genomics ; Glucocorticoids/*pharmacology ; Humans ; RNA, Untranslated ; Receptors, Glucocorticoid/genetics ; Transcription, Genetic ; }, abstract = {Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis.}, } @article {pmid32416485, year = {2020}, author = {Yokoyama, Y and Sakata, H and Uekusa, T and Tajima, Y and Ishimaru, M}, title = {Solitary pancreatic metastasis of gastric cancer with synchronous pancreatic ductal carcinoma: A case report.}, journal = {International journal of surgery case reports}, volume = {70}, number = {}, pages = {164-167}, pmid = {32416485}, issn = {2210-2612}, abstract = {BACKGROUND: There have been a few reports on solitary pancreatic metastases of gastric cancer. We present a case of solitary pancreatic metastasis of gastric cancer with synchronous primary pancreatic ductal carcinoma.

PRESENTATION OF CASE: An 86-year-old man who had undergone total gastrectomy two and half years prior presented with a poorly enhanced tumor in the pancreatic body. We diagnosed pancreatic ductal carcinoma and performed distal pancreatosplenectomy. Histopathologically, the tumor comprised poorly differentiated adenocarcinoma cells mixed with moderately differentiated tubular adenocarcinoma cells that were compatible with metastasis of gastric cancer. There was also invasive ductal carcinoma of the pancreas. The postoperative course was uneventful. Six months after surgery, computed tomography revealed peritoneal dissemination, and he died of recurrence 10 months after surgery.

CONCLUSION: Pancreatic metastasis of gastric cancer with synchronous primary pancreatic cancer can occur and should be considered in the differential diagnosis.}, } @article {pmid32409140, year = {2021}, author = {Ballard, DH and Burton, KR and Lakomkin, N and Kim, S and Rajiah, P and Patel, MJ and Mazaheri, P and Whitman, GJ}, title = {The Role of Imaging in Health Screening: Overview, Rationale of Screening, and Screening Economics.}, journal = {Academic radiology}, volume = {28}, number = {4}, pages = {540-547}, pmid = {32409140}, issn = {1878-4046}, support = {T32 EB021955/EB/NIBIB NIH HHS/United States ; }, mesh = {*Adenocarcinoma ; Advisory Committees ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating ; Diagnostic Imaging ; Humans ; Mass Screening ; United States ; }, abstract = {Imaging screening examinations are growing in their indications and volume to identify conditions at an early, treatable stage. The Radiology Research Alliance's 'Role of Imaging in Health Screening' Task Force provides a review of imaging-based screening rationale, economics, and describes established guidelines by various organizations. Various imaging modalities can be employed in screening, and are often chosen based on the specific pathology and patient characteristics. Prevalent disease processes with identifiable progression patterns that benefit from early potentially curative interventions are ideal for screening. Two such examples include colonic precancerous polyp progression to adenocarcinoma in colon cancer formation and atypical ductal hyperplasia progression to ductal carcinoma in situ and invasive ductal carcinoma in breast cancer. Economic factors in imaging-based screening are reviewed, including in the context of value-based reimbursements. Global differences in screening are outlined, along with the role of various organizational guidelines, including the American Cancer Society, the US Preventive Services Task Force, and the American College of Radiology.}, } @article {pmid32408395, year = {2020}, author = {Solagna, F and Nogara, L and Dyar, KA and Greulich, F and Mir, AA and Türk, C and Bock, T and Geremia, A and Baraldo, M and Sartori, R and Farup, J and Uhlenhaut, H and Vissing, K and Krüger, M and Blaauw, B}, title = {Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.}, journal = {Acta physiologica (Oxford, England)}, volume = {230}, number = {1}, pages = {e13496}, pmid = {32408395}, issn = {1748-1716}, mesh = {Animals ; Chromatin/*chemistry ; Exercise ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*metabolism ; *Physical Conditioning, Animal ; Protein Biosynthesis ; *Serum Response Factor/genetics/metabolism ; *Signal Transduction ; Transcription Factors/*metabolism ; }, abstract = {AIM: Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well-defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise.

METHODS: We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo and treadmill running. We analysed muscle biopsies from human subjects to verify if our findings in murine muscle also translate to exercise in humans.

RESULTS: We identified a new phosphorylation site on Myocardin-Related Transcription Factor B (MRTF-B), a co-activator of serum response factor (SRF). Phosphorylation of MRTF-B is required for its nuclear translocation after exercise and is accompanied by the transcription of the SRF target gene Fos. In addition, high-intensity exercise also remodels chromatin at specific SRF target gene loci through the phosphorylation of histone 3 on serine 10 in myonuclei of both mice and humans. Ablation of the MAP kinase member MSK1/2 is sufficient to prevent this histone phosphorylation, reduce induction of SRF-target genes, and prevent increases in protein synthesis after exercise.

CONCLUSION: Our results identify a new exercise signalling fingerprint in vivo, instrumental for exercise-induced protein synthesis and potentially muscle growth.}, } @article {pmid32408270, year = {2020}, author = {Pedro, J and Cunha, FM and Neto, V and Hespanhol, V and Martins, DF and Guimarães, S and Varela, A and Carvalho, D}, title = {Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?.}, journal = {Endocrinology, diabetes & metabolism case reports}, volume = {2020}, number = {}, pages = {}, pmid = {32408270}, issn = {2052-0573}, abstract = {SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.

LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.}, } @article {pmid32405339, year = {2020}, author = {Santos, JR and Waitzberg, DL and da Silva, IDCG and Junior, TCT and Barros, LRC and Canuto, GAB and Faccio, AT and Yamaguchi, LF and Kato, MJ and Tavares, MFM and Martinez, AC and Logullo, ÂF and Torrinhas, RSMM and Ravacci, G}, title = {Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.}, journal = {Oncotarget}, volume = {11}, number = {18}, pages = {1637-1652}, pmid = {32405339}, issn = {1949-2553}, abstract = {Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science [®]) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.}, } @article {pmid32404955, year = {2020}, author = {Tille, JC and Vieira, AF and Saint-Martin, C and Djerroudi, L and Furhmann, L and Bidard, FC and Kirova, Y and Tardivon, A and Reyal, F and Carton, M and Vincent-Salomon, A}, title = {Tumor-infiltrating lymphocytes are associated with poor prognosis in invasive lobular breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {11}, pages = {2198-2207}, pmid = {32404955}, issn = {1530-0285}, mesh = {Age Factors ; Breast Neoplasms/immunology/metabolism/mortality/*pathology ; Carcinoma, Lobular/immunology/metabolism/mortality/*pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology/*pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi[2] tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.}, } @article {pmid32399324, year = {2020}, author = {Findakly, D and Solsi, A and Arslan, W}, title = {A Novel Combination of Metachronous Primary Malignancies of the Thyroid and Breast in a Patient with Neurofibromatosis Type 1.}, journal = {Cureus}, volume = {12}, number = {4}, pages = {e7590}, pmid = {32399324}, issn = {2168-8184}, abstract = {Neurofibromatosis 1 (NF1) is a genetic condition of variable presentations. It has been shown to increase the risk of multiple cancers. Therefore, NF1 has been identified as a tumor-provoking condition. We present a case of a 39-year-old woman with NF1 who was diagnosed initially with papillary thyroid carcinoma (PTC) and subsequently presented with a painful breast lump. Core biopsy revealed an invasive ductal carcinoma (IDC) for which selective estrogen receptor modulator (SERM) therapy was initiated. A lumpectomy was performed soon after, which confirmed IDC. Following surgery, the patient received a combination of anthracycline and cyclophosphamide (AC), which was later followed by a taxol-based chemotherapy regimen. This study aims to throw light on the rare phenomenon of metachronous malignancy: the occurrence of successive primary cancers in the same patient. We believe that raising awareness regarding the different neoplasms associated with NF1 is important to promote appropriate preemptive screening for early detection of a second primary neoplasm, which can help lower the morbidity and mortality associated with this condition through expedited intervention.}, } @article {pmid32390595, year = {2020}, author = {Liu, TT and Li, XF and Wang, L and Yang, JL}, title = {CD133 expressionand clinicopathologic significance in benign and malignant breast lesions.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {28}, number = {3}, pages = {293-299}, doi = {10.3233/CBM-190196}, pmid = {32390595}, issn = {1875-8592}, mesh = {AC133 Antigen/analysis/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/analysis/*metabolism ; Breast/*pathology/surgery ; Breast Neoplasms/*diagnosis/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/mortality/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/mortality/pathology/surgery ; Carcinoma, Lobular/diagnosis/mortality/pathology ; Diagnosis, Differential ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Hyperplasia/diagnosis/pathology ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness/pathology ; Prognosis ; }, abstract = {BACKGROUND/OBJECTIVE: CD133 is the molecular marker of normal stem cells and progenitor cells and also confirmed as a marker for cancer stem cells in various tumors. The aim of this study is to examine the expression of CD133 and assess its clinicopathologic significance in benign and malignant breast lesions.

METHODS: We analyzed the distribution of CD133 positive cells in breast usual ductal hyperplasia, atypical ductal hyperplasia (ADH), breast ductal carcinoma in situ (DCIS), and invasive breast carcinomas. We then explored the relationship between the CD133 expression and clinicopathologic features using immuno-histochemical staining.

RESULTS: We found that CD133 is not expressed in the cells of normal breast tissue, but the expression rate increased with progression of lesions from usual hyperplasia, through atypical ductal hyperplasia, ductal carcinoma in situ and invasive carcinoma. The positive expression rate of CD133 in breast invasive ductal carcinoma correlated to histological grade, cancer stage, nodal status, metastasis, recurrence, event-free survival and overall survival. There was no significant correlation between CD133 expression and factors such as age, postmenopausal status, histological type, tumor size, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression.

CONCLUSION: CD133 may play an important role in the occurrence and development of breast cancer. CD133 positive breast cancer cells are closely related to invasiveness and its expression may predict a poor prognosis.}, } @article {pmid32381983, year = {2020}, author = {Yabe, S and Oda, G and Nakagawa, T and Kasahara, M and Kumaki, Y and Fujioka, T and Kubota, K and Onishi, L and Uetake, H}, title = {[A Case of Axillary Accessory Breast Cancer Treated via Latissimus Dorsi Musculocutaneous Flap Reconstruction].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {2}, pages = {343-345}, pmid = {32381983}, issn = {0385-0684}, mesh = {Axilla ; *Breast Neoplasms ; Female ; Humans ; *Mammaplasty ; Middle Aged ; *Myocutaneous Flap ; *Superficial Back Muscles ; }, abstract = {A 46-year-old woman visited our hospital with the chief complaint of left axillary mass enlargement, which she had been aware of for 8 years. Palpation revealed that the mass was 15mm in size. Redness and gathering of the skin were also observed. Mammographic imaging of the left axilla revealed an irregular mass with skin infiltration. Breast ultrasonography revealed a low echo mass in the left axilla, which was continuous from the skin. Core needle biopsy was used to diagnose the tumor as an invasive ductal carcinoma. No other lesions were observed in the breast, and primary lesions were not found in any other organs. The patient was diagnosed with axillary accessory breast cancer and underwent local extensive resection and axillary lymph node dissection. Because the skin defect was widespread, we performed axillary reconstruction using the latissimus dorsi musculocutaneous flap to prevent upper limb contracture. At present, she can move her upper limbs and lymphedema has not been observed. In cases of axillary accessory breast cancer with skin infiltration, reconstruction using the latissimus dorsi musculocutaneous flap can be a useful procedure.}, } @article {pmid32381877, year = {2020}, author = {Tsuruda, Y and Masuda, T and Hayashi, N and Noda, M and Otsu, H and Kuroda, Y and Eguchi, H and Tanaka, F and Natsugoe, S and Mimori, K}, title = {[Axillary Arterial Bleeding with Administration of Bevacizumab plus Paclitaxel in a Patient with Recurrent Breast Cancer-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {1}, pages = {117-119}, pmid = {32381877}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Bevacizumab ; *Breast Neoplasms/drug therapy ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Paclitaxel ; }, abstract = {We report a case of axillary arterial bleeding after administration of bevacizumab plus paclitaxel in a patient with recurrent breast cancer.A 50-year-old woman with invasive ductal carcinoma of the left breast underwent mastectomy and sentinel node biopsy.She was administered 4 courses of docetaxel and cyclophosphamide as adjuvant chemotherapy.Twenty -eight months after the surgery, she developed axillary lymph node recurrence with pain and upper-limb paralysis.Initially, radiation therapy was performed in the axilla combined with the oral administration of TS-1.However, the response was inadequate. Subsequently, bevacizumab plus paclitaxel was administered.After 2 courses, we observed remarkable shrinkage of the axillary tumor.However, she experienced massive bleeding from the axillary artery.As the bleeding recurred, we ligated the axillary artery.Caution is required while administrating bevacizumab in cases of tumors located close to the major blood vessels.}, } @article {pmid32381867, year = {2020}, author = {Tamaoki, M and Nio, Y and Tamaoki, M and Sakamoto, M and Uesugi, K and Sakamoto, T and Imai, S and Maruyama, R}, title = {[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {47}, number = {1}, pages = {77-81}, pmid = {32381867}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/radiotherapy ; Female ; *Hemangiosarcoma/etiology ; Humans ; Japan ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; *Neoplasms, Radiation-Induced ; *Skin Neoplasms ; }, abstract = {We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.}, } @article {pmid32380439, year = {2020}, author = {Rodriguez-Ibarria, NG and Pinar, MB and García, L and Cabezón, MA and Lloret, M and Rey-Baltar, MD and Rdguez-Melcón, JI and Lara, PC}, title = {Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {52}, number = {}, pages = {45-49}, pmid = {32380439}, issn = {1532-3080}, mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy ; Radiotherapy Dosage ; }, abstract = {Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.}, } @article {pmid32380362, year = {2020}, author = {Erel, H and Zivony, A and Levy, DA}, title = {Cognitive processes in aging effects on attentional alerting.}, journal = {Neurobiology of aging}, volume = {92}, number = {}, pages = {28-33}, doi = {10.1016/j.neurobiolaging.2020.03.022}, pmid = {32380362}, issn = {1558-1497}, mesh = {Adult ; Aged ; Aging/*psychology ; *Attention ; *Cognition ; *Cues ; Female ; Humans ; Male ; Orientation ; Young Adult ; }, abstract = {Alerting, the process of achieving and maintaining a state of optimal vigilance, is crucial for detecting relevant stimuli and task performance. Age-related decline in the ability to use alerting cues is widely reported and attributed to changes in noradrenergic signaling. However, it remains to be determined whether aging affects all forms of alerting cues equally and whether older adults differently modulate their alerting sensitivity based on differences in cue predictivity relevant to the target task. We examined the performance of 135 younger adults and 103 older adults on three versions of the Attention Networks Test, using locational but spatially nonpredictive visual cues, locational spatially predictive visual cues, and spatially predictive auditory cues. Analysis of alerting effects indicated that while older adults derived less benefit from visual alerting cues than younger adults, they used auditory alerting cues equally well. Furthermore, cue spatial predictivity did not impact on aging effects on alerting. This heterogeneity in aging effects on alerting may indicate that they result primarily from cognitive rather than neuromodulatory changes.}, } @article {pmid32378053, year = {2020}, author = {O'Toole, SA and Spillane, C and Huang, Y and Fitzgerald, MC and Ffrench, B and Mohamed, B and Ward, M and Gallagher, M and Kelly, T and O'Brien, C and Ruttle, C and Bogdanska, A and Martin, C and Mullen, D and Connolly, E and McGarrigle, SA and Kennedy, J and O'Leary, JJ}, title = {Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {3}, pages = {571-580}, pmid = {32378053}, issn = {1573-7217}, support = {CSA-2012-9//Health Research Board Ireland/ ; IPP2017 0616 in conjunction with Becton Dickinson//Enterprise Ireland/ ; }, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Carcinoma, Lobular/drug therapy/metabolism/*pathology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy/*mortality ; Neoplasm Grading ; Neoplastic Cells, Circulating/drug effects/*pathology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system.

METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ[2] or ANOVA was performed in SPSS 24.0 statistics software for associations.

RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05.

CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.}, } @article {pmid32371885, year = {2020}, author = {Schwarz, D and Hidmark, AS and Sturm, V and Fischer, M and Milford, D and Hausser, I and Sahm, F and Breckwoldt, MO and Agarwal, N and Kuner, R and Bendszus, M and Nawroth, PP and Heiland, S and Fleming, T}, title = {Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {7593}, pmid = {32371885}, issn = {2045-2322}, mesh = {Animals ; Biopsy ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/*diagnostic imaging/etiology/*pathology ; Disease Models, Animal ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging/methods/standards ; Mice ; Microscopy ; Microscopy, Electron ; }, abstract = {In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.}, } @article {pmid32367518, year = {2020}, author = {Zhu, AQ and Li, XL and An, LW and Guo, LH and Fu, HJ and Sun, LP and Xu, HX}, title = {Predicting Axillary Lymph Node Metastasis in Patients With Breast Invasive Ductal Carcinoma With Negative Axillary Ultrasound Results Using Conventional Ultrasound and Contrast-Enhanced Ultrasound.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {39}, number = {10}, pages = {2059-2070}, doi = {10.1002/jum.15314}, pmid = {32367518}, issn = {1550-9613}, support = {2019LJ21//Shanghai Municipal Health Commission/ ; SHSLCZDZK03502//Shanghai Municipal Health Commission/ ; 19441903200//Science and Technology Commission of Shanghai Municipality/ ; 19DZ2251100//Science and Technology Commission of Shanghai Municipality/ ; 22120190213//Fundamental Research Funds for the Central Universities/ ; 81725008//National Natural Science Foundation of China/ ; 81927801//National Natural Science Foundation of China/ ; }, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast/diagnostic imaging ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis/diagnostic imaging ; Retrospective Studies ; }, abstract = {OBJECTIVES: The purpose of this study was to establish a scoring system for predicting axillary lymph node metastasis (ALNM) in patients with breast invasive ductal carcinoma with negative axillary ultrasound (US) results.

METHODS: In this retrospective study, 156 breast invasive ductal carcinoma lesions from 156 women were retrospectively enrolled. The features of conventional US and contrast-enhanced ultrasound (CEUS) qualitative enhancement patterns and quantitative enhancement parameters were analyzed. Subsequently, a scoring system was created by a multivariate logistic regression analysis.

RESULTS: The results found that 60 patients (38%) showed ALNM. A scoring system was defined as risk score = 1.75 × (if lesion size ≥20 mm) + 1.93 × (if uncircumscribed margin shown on conventional US) + 1.77 × (if coarse or twisting penetrating vessels shown on CEUS). When the risk scores were less than 1.75, 1.75 to 1.93, 1.94 to 3.70, and 3.70 or higher, the risk rates of ALNM were 0% (0 of 9), 10.7% (5 of 46), 29.2% (14 of 48) and 77.4% (41 of 53), respectively. In comparison with conventional US alone, the scoring system using the combination of conventional US and CEUS showed better discrimination ability in terms of the area under the curve (0.830 versus 0.777; P = .037).

CONCLUSIONS: A scoring system based on conventional US and CEUS may improve the prediction of ALNM.}, } @article {pmid32367072, year = {2020}, author = {Eggemann, H and Brucker, C and Schrauder, M and Thill, M and Flock, F and Reinisch, M and Costa, SD and Ignatov, A}, title = {Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis.}, journal = {British journal of cancer}, volume = {123}, number = {1}, pages = {33-37}, pmid = {32367072}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/adverse effects/therapeutic use ; Aromatase Inhibitors/adverse effects/*therapeutic use ; Breast Neoplasms, Male/*drug therapy/pathology ; Disease-Free Survival ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/pathology ; Prognosis ; Tamoxifen/adverse effects/*therapeutic use ; }, abstract = {BACKGROUND: Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients.

METHODS: In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018. The primary endpoint was disease-free survival (DFS).

RESULTS: Between May 2009 and June 2018, 448 men with breast cancer were identified, with a median age at diagnosis of 69 years (range 27-96 years). The median follow-up was 39 months (range 3-89 months). Most tumours were larger than 20 mm; invasive ductal carcinoma was of no special histological type and with an intermediate grade of differentiation. Almost half of the men were diagnosed with positive axillary lymph nodes (43.5%). Hormone receptor (HR) positivity was observed in 98.4% of the patients. Notably, DFS among men who did not receive tamoxifen was significantly reduced as compared with those who underwent tamoxifen therapy (P = 0.002). The recurrence rate and mortality in the group of patients without and with tamoxifen treatment were 18.2% and 11.2%, respectively. The most common localisation of metastases was the bone. After adjustment for prognostic factors, we found that tamoxifen was found to reduce the recurrence rate by 68% (hazard ratio HR = 0.32; 95% confidence interval, CI: 0.14-0.74).

CONCLUSIONS: Tamoxifen treatment was associated with improved DFS for MBC patients.

CLINICAL TRIAL REGISTRATION: DRKS00009536.}, } @article {pmid32365829, year = {2020}, author = {Cortes-Urrea, C and Bueno-Gutiérrez, F and Solarte, M and Guevara-Burbano, M and Tobar-Tosse, F and Vélez-Varela, PE and Bonilla, JC and Barreto, G and Velasco-Medina, J and Moreno, PA and Rivas, JL}, title = {Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.}, journal = {Biomolecules}, volume = {10}, number = {5}, pages = {}, pmid = {32365829}, issn = {2218-273X}, support = {PI18/00591//Instituto de Salud Carlos III/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; *Exome ; Female ; Humans ; Middle Aged ; *Mutation ; Oncogenes ; }, abstract = {Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.}, } @article {pmid32362500, year = {2020}, author = {Dianatinasab, M and Rezaian, M and HaghighatNezad, E and Bagheri-Hosseinabadi, Z and Amanat, S and Rezaeian, S and Masoudi, A and Ghiasvand, R}, title = {Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e516-e528}, doi = {10.1016/j.clbc.2020.03.007}, pmid = {32362500}, issn = {1938-0666}, mesh = {Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diet Surveys/*statistics & numerical data ; *Feeding Behavior ; Female ; Humans ; Risk Assessment/statistics & numerical data ; Risk Factors ; }, abstract = {The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I[2] = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I[2] = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I[2] = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I[2] = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I[2] = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.}, } @article {pmid34296092, year = {2020}, author = {Freche, D and Naim-Feil, J and Hess, S and Peled, A and Grinshpoon, A and Moses, E and Levit-Binnun, N}, title = {Phase-Amplitude Markers of Synchrony and Noise: A Resting-State and TMS-EEG Study of Schizophrenia.}, journal = {Cerebral cortex communications}, volume = {1}, number = {1}, pages = {tgaa013}, pmid = {34296092}, issn = {2632-7376}, abstract = {The electroencephalogram (EEG) of schizophrenia patients is known to exhibit a reduction of signal-to-noise ratio and of phase locking, as well as a facilitation of excitability, in response to a variety of external stimuli. Here, we demonstrate these effects in transcranial magnetic stimulation (TMS)-evoked potentials and in the resting-state EEG. To ensure veracity, we used 3 weekly sessions and analyzed both resting-state and TMS-EEG data. For the TMS responses, our analysis verifies known results. For the resting state, we introduce the methodology of mean-normalized variation to the EEG analysis (quartile-based coefficient of variation), which allows for a comparison of narrow-band EEG amplitude fluctuations to narrow-band Gaussian noise. This reveals that amplitude fluctuations in the delta, alpha, and beta bands of healthy controls are different from those in schizophrenia patients, on time scales of tens of seconds. We conclude that the EEG-measured cortical activity patterns of schizophrenia patients are more similar to noise, both in alpha- and beta-resting state and in TMS responses. Our results suggest that the ability of neuronal populations to form stable, locally, and temporally correlated activity is reduced in schizophrenia, a conclusion, that is, in accord with previous experiments on TMS-EEG and on resting-state EEG.}, } @article {pmid32357428, year = {2020}, author = {Wang, Z and Dong, Y and Liu, W and Ma, Z}, title = {A Novel Fault Diagnosis Approach for Chillers Based on 1-D Convolutional Neural Network and Gated Recurrent Unit.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {9}, pages = {}, pmid = {32357428}, issn = {1424-8220}, support = {No. 4192005//Beijing Municipal Natural Science Foundation/ ; }, abstract = {The safety of an Internet Data Center (IDC) is directly determined by the reliability and stability of its chiller system. Thus, combined with deep learning technology, an innovative hybrid fault diagnosis approach (1D-CNN_GRU) based on the time-series sequences is proposed in this study for the chiller system using 1-Dimensional Convolutional Neural Network (1D-CNN) and Gated Recurrent Unit (GRU). Firstly, 1D-CNN is applied to automatically extract the local abstract features of the sensor sequence data. Secondly, GRU with long and short term memory characteristics is applied to capture the global features, as well as the dynamic information of the sequence. Moreover, batch normalization and dropout are introduced to accelerate network training and address the overfitting issue. The effectiveness and reliability of the proposed hybrid algorithm are assessed on the RP-1043 dataset; based on the experimental results, 1D-CNN_GRU displays the best performance compared with the other state-of-the-art algorithms. Further, the experimental results reveal that 1D-CNN_GRU has a superior identification rate for minor faults.}, } @article {pmid32354932, year = {2020}, author = {Fujii, T and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Shirabe, K}, title = {Relationship Between FDG Uptake and the Platelet/lymphocyte Ratio in Patients With Breast Invasive Ductal Cancer.}, journal = {In vivo (Athens, Greece)}, volume = {34}, number = {3}, pages = {1365-1369}, pmid = {32354932}, issn = {1791-7549}, mesh = {Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/etiology/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Leukocyte Count ; *Lymphocyte Count ; Middle Aged ; Neutrophils ; *Platelet Count ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Tumor Microenvironment ; }, abstract = {BACKGROUND/AIM: We investigated the relationship between F18-fluorodeoxyglucose (FDG) uptake and the platelet/lymphocyte ratio (PLR), as both represent inflammation.

PATIENTS AND METHODS: We retrospectively analyzed the cases of 143 consecutive invasive ductal carcinoma patients who had undergone preoperative FDG-PET and surgery. We divided the patients into groups based on their maximum standardized uptake value (SUVmax) values: low (<2.5) and high (≥2.5) and based on their PLRs: low (<130) and high (≥130). We determined the relationships between the SUVmax or PLR and clinicopathological features.

RESULTS: Seventy-three patients (51.0%) had a high SUVmax in their primary tumor. There were significant associations between SUVmax and the PLR. A multivariate analysis revealed that high PLR, but not NLR, was independent factor associated with a high SUVmax. Seventy-four patients (51.7%) had a high PLR; The factors significantly associated with high PLR were large tumor size, presence of node metastasis, presence of vascular invasion, high NLR, and high SUVmax.

CONCLUSION: In breast cancer patients, the PLR is independently associated with the SUVmax, but not with recurrent disease. In breast cancer patients with a high SUVmax and/or PLR, these values may reflect the tumor microenvironment.}, } @article {pmid32354370, year = {2020}, author = {Hedrick, K and Armstrong, G and Coffey, G and Borschmann, R}, title = {Self-harm among asylum seekers in Australian onshore immigration detention: how incidence rates vary by held detention type.}, journal = {BMC public health}, volume = {20}, number = {1}, pages = {592}, pmid = {32354370}, issn = {1471-2458}, support = {Not applicable//Australian government Post-Graduate Research Training Grant/ ; 1104464//NHMRC Early Career Fellowship/ ; 1138096//NHMRC Early Career Fellowship/ ; }, mesh = {Adult ; Australia/epidemiology ; Emigration and Immigration/*statistics & numerical data ; Female ; Humans ; Incidence ; Male ; Mental Disorders/epidemiology ; Refugees/psychology/*statistics & numerical data ; Self-Injurious Behavior/*epidemiology/psychology ; }, abstract = {BACKGROUND: Detained asylum seekers are at increased risk of self-harm, and the type of detention in which they are held may further exacerbate this risk. In Australia, there are four types of closed (or held) immigration detention for people seeking asylum, with varying levels of security and supports: Immigration Detention Centres [IDCs], Immigration Transit Accommodation [ITAs], Immigration Residential Housing [IRH], and Alternative Places of Detention [APODs]. The objective of this study was to examine the variation in the incidence and method(s) of self-harm among asylum seekers in Australian onshore immigration detention, according to the type of detention in which they are held.

METHODS: We obtained data on all self-harm incidents reported among asylum seekers in Australian onshore immigration detention according to held detention type, as well as individual facility, between 1 August 2014 and 31 July 2015, by Freedom of Information. We calculated self-harm episode rates per 1000 asylum seekers using the average population figures for held detention type, as well as for each individual facility comprising the main types of held detention. Method(s) used to self-harm was also extracted for the main sub-populations.

RESULTS: The study included 560 episodes of self-harm. Individual facility rates of self-harm ranged from 91 per 1000 asylum seekers (95% CI 72-110) in Yongah Hill IDC to 533 per 1000 asylum seekers (95% CI 487-578) in Perth IDC. On average, calculated self-harm episode rates were highest among asylum seekers in: Immigration Transit Accommodation facilities, 452/1000 (95% CI 410-493); Alternative Places of Detention, 265/1000 (95% CI 233-296); and Immigration Detention Centres, 225/1000 (95% CI 195-254). The most frequently reported methods of self-harm across the main types of held detention were: cutting (35.2%), self-battery (34.8%), and attempted hanging (11.1%).

CONCLUSIONS: Self-harm rates for asylum seekers in all types of closed immigration detention were many times higher than rates found in the general population. Average rates were not lower in facilities with lower security features.}, } @article {pmid32353271, year = {2020}, author = {Klomek, AB}, title = {Suicide prevention during the COVID-19 outbreak.}, journal = {The lancet. Psychiatry}, volume = {7}, number = {5}, pages = {390}, pmid = {32353271}, issn = {2215-0374}, mesh = {Anxiety ; Betacoronavirus ; COVID-19 ; Communication ; Coronavirus Infections/epidemiology/*psychology ; Death ; Depression ; Disease Outbreaks ; Humans ; *Mental Health Services ; Pandemics ; Pneumonia, Viral/epidemiology/*psychology ; SARS-CoV-2 ; Suicide/psychology ; *Suicide Prevention ; }, } @article {pmid32343605, year = {2021}, author = {Liu, CR and Meng, FH}, title = {DNASE1L2, as a Carcinogenic Marker, Affects the Phenotype of Breast Cancer Cells Via Regulating Epithelial-Mesenchymal Transition Process.}, journal = {Cancer biotherapy & radiopharmaceuticals}, volume = {36}, number = {2}, pages = {180-188}, doi = {10.1089/cbr.2019.3504}, pmid = {32343605}, issn = {1557-8852}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Proliferation/physiology ; Deoxyribonuclease I/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Middle Aged ; Phenotype ; Prognosis ; Transfection ; }, abstract = {Purpose: The authors explore the role of DNASE1L2 in breast cancer (BC) and its affect on the cell phenotype. Methods: Breast invasive ductal carcinoma RNA-Seq data set was downloaded from The Cancer Genome Atlas database for analyzing DNASE1L2 levels. Overall survival curve was plotted by Kaplan-Meier methods. The correlations between DNASE1L2 expression and clinical characteristics were analyzed by chi-square tests. Cox regression models were implemented for analyzing the potential prognosticators of BC. Small interference RNA-DNASE1L2 and pcDNA3.1-DNASE1L2 were transfected into BC cells to silence and overexpress DNASE1L2, respectively. Relative mRNA and protein levels were determined by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Cell counting Kit-8, clone formation, and Transwell assays were employed to measure the proliferative, invasive, and migratory abilities. Results: Bioinformatics analysis showed that the levels of DNASE1L2 were found to be elevated in BC tissues, which was further proved by qRT-PCR tests. Besides, high expression of DNASE1L2 was dramatically led to a poor overall survival. Furthermore, DNASE1L2 expression was remarkably associated with age and pathologic-stage. Silencing DNASE1L2 showed an inhibitory effect on the proliferation, invasion, and migration of MCF7 cells, whereas overexpression of DNASE1L2 in BT549 cells presented the opposite results. Mechanistically, downregulation of DNASE1L2 could significantly enhance the levels of E-cadherin, as well as suppress the levels of Vimentin, N-cadherin and Snail, whereas upregulation of DNASE1L2 showed the reverse outcomes. Conclusion: This study for the first time demonstrated that DNASE1L2 was upregulated in BC cells, and acted as an oncogene to affect the phenotype of BC cells by modulating the epithelial-mesenchymal transition process, which suggested that DNASE1L2 might be considered as a useful biomarker for BC therapeutics.}, } @article {pmid32342914, year = {2020}, author = {AlZaman, A and Ali, E and Mohamad, B and Islam, M and AlZaman, E and AlZaman, Y}, title = {The Association Between Clinicopathological Features and Molecular Markers in Bahraini Women With Breast Cancer.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {32}, pages = {19-25}, pmid = {32342914}, issn = {2078-2101}, mesh = {Bahrain ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; }, abstract = {INTRODUCTION: Breast cancer (BC) is a heterogenous disease and a major public health burden in Bahrain. Based on hormone receptor status (ER, PR, and HER2), BC can be divided into four molecular subtypes: Luminal A, Luminal B, HER2+, and Triple negative, each of which display distinct clinical behaviour.

PATIENTS AND METHODS: This retrospective study included 216 patients diagnosed with BC between November 2017 and May 2019 at the Bahrain oncology centre. The clinicopathological characteristics (age, size of tumour, grade, lymph node involvement, metastasis) were examined, in addition to immunohistochemical markers (ER, PR, and HER2), and BRCA 1 and 2 status (when indicated). SPSS was used to evaluate the correlation between the molecular subtypes and different clinicopathological features.

RESULTS: BC in Bahraini women was relatively of large size (68.5% larger than 20mm), with frequent metastasis to the lymph nodes (57.4%). The mean age at diagnosis was 51.8 years ±11.5, with invasive ductal carcinoma (IDC) being the most common histological type (90.3%). The most common molecular subtype was Luminal A (60.2%), followed respectively by luminal B (19%), triple negative (13.4%) and HER-2 (7.4%).

DISCUSSION: Significant differences were found between the subtypes regarding grade (p=0.001) and BRCA mutation status (0.001). Triple negative subtype was associated with highly-aggressive behaviour compared to the other subtypes. It presented at younger age, with high grade, large tumor size, and predominance to distant metastasis. It was also linked with positive BRCA mutations.

CONCLUSION: A significant proportion of Bahraini females with BC present with aggressive features (i.e. younger age, poorly differentiated tumors, and lymph node involvement). Expectedly this was associated with underlying aggressive molecular subtypes (namely TNBC). The aggressive properties of such molecular subtype mandate further molecular testing to identify more accurate prognostic and predictive targets for effective treatment and risk reduction strategies.}, } @article {pmid34621499, year = {2020}, author = {Krauze, AV and Megan, M and Theresa, CZ and Peter, M and Shih, JH and Tofilon, PJ and Rowe, L and Gilbert, M and Camphausen, K}, title = {The addition of Valproic acid to concurrent radiation therapy and temozolomide improves patient outcome: a Correlative analysis of RTOG 0525, SEER and a Phase II NCI trial.}, journal = {Cancer studies and therapeutics}, volume = {5}, number = {1}, pages = {}, pmid = {34621499}, issn = {2002-7184}, support = {Z01 SC010373/ImNIH/Intramural NIH HHS/United States ; ZIA SC010372/ImNIH/Intramural NIH HHS/United States ; ZIA SC010373/ImNIH/Intramural NIH HHS/United States ; }, abstract = {PURPOSE/OBJECTIVES: Valproic Acid (VPA) is an antiepileptic agent with HDACi (histone deacetylase inhibitor) activity shown to radiosensitize glioblastoma (GBM) cells. We evaluated the addition of VPA to standard radiation therapy (RT) and temozolomide (TMZ) in an open-label, phase II study (NCI-06-C-0112). The intent of the current study was to compare our patient outcomes with modern era standard of care data (RTOG 0525) and general population data (SEER 2006-2013).

MATERIALS/METHODS: 37 patients with newly diagnosed GBM were treated in a phase II NCI trial with daily VPA (25 mg/kg) in addition to concurrent RT and TMZ (2006 - 2013) and 411 patients with newly diagnosed GBM were treated in the standard TMZ dose arm of RTOG 0525 (2006 - 2008). Using the SEER database, adult patients (age > 15) with diagnostic codes 9440-9443 (third edition (IDC-O-3) diagnosed between 2006 - 2013 were identified and 6083 were included in the analysis. Kaplan-Meier method was used to estimate OS and PFS. The effect of patient characteristics and clinical factors on OS and PFS was analyzed using univariate analysis and a Cox regression model. A landmark analysis was performed to correlate recurrence to OS and conditional probabilities of surviving an additional 12 months at diagnosis, 6, 12, 18, 24 and 30 months were calculated for both the trial data and the SEER data.

RESULTS: Updated median OS in the NCI cohort was 30.9m (22.2- 65.6m), compared to RTOG 0525 18.9m (16.8-20.3m) (p= 0.007) and the SEER cohort of 11m. Median PFS in the NCI cohort was 11.1m (6.6 - 49.6m) compared to RTOG 0525 with a median PFS of 7.5m (6.9-8.2m) (p = 0.004). Younger age, class V RPA and MGMT status were significant for PFS in both the NCI cohort and the RTOG 0525 cohort, in addition KPS was also significant for OS. In comparison to RTOG 0525, the population in the NCI cohort had a more favorable KPS and RPA, and a higher proportion of patients receiving bevacizumab after protocol therapy however with the exception of RPA (V) (8% vs 18%) (0.026), the effects of these factors on PFS and OS were not significantly different between the two cohorts.

CONCLUSION: Previously reported improvements in PFS and OS with the addition of VPA to concurrent RT and TMZ in the NCI phase II study were confirmed by comparison to both a trial population receiving standard of care (RTOG 0525) and a contemporary SEER cohort. These results provide further justification of a phase III trial of VPA/RT/TMZ.}, } @article {pmid34191158, year = {2019}, author = {Aarstad, EM and Nordhaug, P and Naghavi-Behzad, M and Larsen, LB and Gerke, O and Hildebrandt, MG}, title = {Prevalence of focal incidental breast uptake on FDG-PET/CT and risk of malignancy: a systematic review and meta-analysis.}, journal = {European journal of hybrid imaging}, volume = {3}, number = {1}, pages = {16}, pmid = {34191158}, issn = {2510-3636}, support = {//Danmarks Frie Forskningsfond/ ; //Syddansk Universitet/ ; }, abstract = {BACKGROUND: FDG-PET/CT is increasingly used for oncologic and inflammatory diseases. Focal incidental FDG uptake occurs rarely in breast tissue but has often significant consequences. This study aimed to systematically review literature regarding focal incidental breast uptake (FIBU) on FDG-PET/CT in order to yield an update on the prevalence and risk of malignancy for FIBU.

METHODS: A systematic search for relevant articles published between 2012 and 2018 was performed through MEDLINE, Embase, and Cochrane databases. Studies addressing the detection of FIBU in patients without a previous history of breast malignancy were included. The QUADAS-2 was used for quality assessment, and eligible data were pooled using a fixed-effects model. I[2] was calculated for the heterogeneity between studies.

RESULTS: Eight studies containing 180,002 scans were included in the systematic review. The median prevalence of FIBU for both genders was 0.52% (range 0.18-22.5%). Prevalence for women was mentioned separately in five studies and varied from 0.51 to 23.5%. One study reporting a high prevalence was based on patients being staged for known malignancy, and the word "breast" was used in the search, which may have caused selection bias. Data from four studies were eligible for meta-analysis. A high degree of heterogeneity was observed for prevalence data (I[2] of 97.5%), while moderate heterogeneity was observed for data on malignancy risk assessment (I[2] of 62.8%). The pooled prevalence of FIBU in women was 0.61% (range 0.56-0.66%), and the pooled prevalence of malignancy of FIBUs was 38.7% (range 34.4-43.0%). The most commonly detected malignancy was invasive ductal carcinoma.

CONCLUSION: FIBU occurs rarely on FDG-PET/CT for female patients but yields a high risk of malignancy according to the results of published papers. Therefore, it should be considered relevant to further elucidate patients with incidentally detected FDG uptake in breast in clinical practice.}, } @article {pmid33343986, year = {2019}, author = {Fehl, A and Ferrari, S and Wecht, Z and Rosenzweig, M}, title = {Breast Cancer in the Transgender Population.}, journal = {Journal of the advanced practitioner in oncology}, volume = {10}, number = {4}, pages = {387-394}, pmid = {33343986}, issn = {2150-0878}, abstract = {ES is a 41-year-old transgender male who presented to medical oncology as a referral from surgical oncology for T2N0M0 right breast cancer. At that time, he was receiving weekly testosterone injections intramuscularly at 0.25 mg, and had been on this regimen for 7 months. He was planning bilateral mastectomies in the spring. That winter, he palpated a mass in his right breast, and imaging revealed a 2.5-cm hypoechoic mass. A biopsy of the mass revealed invasive ductal carcinoma, with a nuclear grade of 3. His tumor was estrogen receptor positive (H-score of 180), progesterone receptor positive (H-score of 90), androgen receptor positive (H-score of 220), and HER-2/neu positive by FISH, with a Ki-67 of 90%. The clinical experience of ES illustrates challenges common to the sexual and gender minority population. ES presented to the clinic with a female friend. At that time, his name and gender in the electronic medical record (EMR) matched his driver's license, and not his preferred name or gender. Consequently, when he was called from the waiting room, he was called by his former name. The staff had not been notified of the appropriate name or pronoun to use prior to ES's arrival, and consequently was associating ES with a female gender, as indicated in the EMR. When the question about menstrual status was addressed, he stated that he had not had a period in 7 months since beginning testosterone treatment. The medical assistant questioned the use of testosterone, and ES had to explain his gender reassignment journey. By the time the physician assistant (PA) entered the room to perform the first part of the shared visit, ES was visibly upset, expressing anger with nonverbal cues. During the conversation, the PA did not acknowledge or establish the relationship of ES's female friend. The PA did not address the issue of gender identity, the use of testosterone, or plans for reassignment surgery. The physician also deferred discussion of gender reassignment during his portion of the visit and, without asking about gender reassignment, recommended cessation of testosterone therapy. Neoadjuvant docetaxel/cyclophosphamide/trastuzumab/pertuzumab was ordered, and ES agreed to treatment, but declined following the suggestion to stop testosterone. At each treatment visit, ES had to check in at the desk with his former name, resulting in confusion from the staff. With each lab draw, his name and birthdate were confirmed using the former name. With every administration of chemotherapy, double-nurse verification at the chairside was performed by reading his arm band and comparing it to the drug label. For each visit, ES had to use his old name six times. With new staff assigned to him each week, he felt pressured to explain his gender identity to several new people at each visit. At one particular visit, a patient's family in the next cubicle overheard this conversation, and ES overheard them discussing and laughing about his gender identity. ES dreaded his chemotherapy appointments not just due to the expected toxicity, but also because of the insensitivity toward his chosen gender. ES tolerated chemotherapy and proceeded to surgery. He underwent bilateral mastectomies by the surgical oncologist, who had discussed his gender reassignment with him and had referred him to plastic surgery for co-management of the surgical intervention. The plastic surgery team planned for reconstruction to include skin and soft-tissue rearrangement to give an incision line along the lower border of the pectoralis for better male cosmetic outcomes. Together, they performed bilateral mastectomies with right sentinel lymph node biopsy, horizontal mastopexy, and nipple-areolar grafting. Ultimately, the pathology revealed a complete response, and ES was pleased with the cosmetic outcome. ES was then started on tamoxifen. Again it was suggested that he discontinue testosterone therapy. He determined that he was more comfortable with an increased risk of recurrence than he was with feminine physical characteristics and chose to continue testosterone. After 6 weeks of tamoxifen, his menses resumed. He elected to discontinue tamoxifen. He had no more vaginal bleeding after that episode. He was referred for bilateral salpingo-oopherectomy (BSO), with the intent to treat with an aromatase inhibitor. He proceeded with BSO and opted against the aromatase inhibitor, citing concerns about unknown interactions with gender-affirming medication. He completed 1 year of trastuzumab (Herceptin) and continued surveillance visits.}, } @article {pmid33178931, year = {2019}, author = {van Nijnatten, TJ and Jochelson, MS and Pinker, K and Keating, DM and Sung, JS and Morrow, M and Smidt, ML and Lobbes, MB}, title = {Differences in degree of lesion enhancement on CEM between ILC and IDC.}, journal = {BJR open}, volume = {1}, number = {1}, pages = {20180046}, pmid = {33178931}, issn = {2513-9878}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: To investigate differences in the degree of enhancement on contrast-enhanced mammography (CEM) between patients with invasive lobular (ILC) and infiltrating ductal carcinoma (IDC) not otherwise specified.

METHODS AND MATERIALS: Between 2010 and 2017, all patients diagnosed with ILC and who underwent CEM were included for this dual center study. Twenty-two patients with IDC, matched by size, were identified for comparison. Three independent readers, blinded for histopathology results, re-evaluated all CEM exams to determine degree of lesion enhancement according to a previously defined scoring scale ranging from minimal to strong enhancement. Interobserver agreement among the three readers was calculated by quadratic weighted κ coefficient.

RESULTS: 44 patients were included: 22 patients with ILC and 22 patients with IDC. There were no significant differences in age, mean tumor size, tumor grade or receptor status between the two subgroups. Degree of lesion enhancement on CEM was more often considered weak in case of ILC compared to IDC according to two out of three readers (31.8% vs 4.5 %, p = 0.045 and 22.7 vs 4.5 %, p = 0.185). All other lesions showed moderate or strong enhancement. Interobserver agreement between the three independent readers was good (κ = 0.72).

CONCLUSION: In patients with ILC, degree of lesion enhancement on CEM appears to be more often weak than in infiltrating ductal carcinoma not otherwise specified. Radiologists should be aware that weakly enhancing lesions may in fact be malignant and particularly invasive lobular cancers.

ADVANCES IN KNOWLEDGE: Three independent readers evaluated 44 CEM cases with ILC or IDC. Degree of lesion enhancement seems more often weak in case of ILC. Radiologists should be aware of ILC in case of weak CEM enhancement.}, } @article {pmid33553054, year = {2018}, author = {Aghahowa, ME and Salu, IK and Ezike, KN and Bassey, OS and Umar, MU and Etim, OA and Okwudire-Ejeh, IA}, title = {ADVANCED, RECURRENT, INVASIVE CRIBIFORM CARCINOMA OF THE BREAST IN A 17-YEAR-OLD MALE: A CASE REPORT.}, journal = {Journal of the West African College of Surgeons}, volume = {8}, number = {4}, pages = {114-124}, pmid = {33553054}, issn = {2276-6944}, abstract = {INTRODUCTION: Male breast cancers (MBC) are relatively rare, accounting for about 1% of all male cancers in the US and 0.6% of breast cancers worldwide. In Nigeria, though the incidence varies per region, with a range of 3.4 to 9%, it is noted to be increasing. Gynaecomastia is a well-documented predisposing factor as well as endogenous and exogenous oestrogen. The most common histological subtype of male breast cancer is the invasive ductal carcinoma. Invasive cribriform carcinoma, ICC, is an extremely rare variant, with no more than 10 cases reported worldwide and, when present, has been diagnosed in patients above 40 years old.

CASE REPORT: We present the case of a 17 year-old, male undergraduate student, who presented to our clinic on account of a recurrent, painless, right breast lump. Three years earlier he had had a right breast lump excised at another health facilityand this was diagnosed histopathologicallyas invasive cribriform carcinoma. The only known predisposing factor was an initial lump, excised when he was 10 years old, and diagnosed histologically as gynaecomastia.He had surgical excision and axillary lymph node clearance,and histopathology re-confirmed high grade invasive cribriform carcinoma with multiple lymph node metastases, while immunohistochemistry showed a triple negative signature. He was thereafter referred for adjuvant treatment and has responded well to radiotherapy.

CONCLUSION: There is need for a high index of suspicion in all cases of gynaecomastia, and all such patients should be followed up. Prompt intervention, recourse to histology, and where indicated, immunohistochemistry, are important.}, } @article {pmid33168499, year = {2018}, author = {Pan, Z and Yao, M and Chen, Y and Deng, J and Yan, M and Gao, J}, title = {[Abnormal granulocyte differentiation and the paradoxical switch of transforming growth factor-β1 in breast cancer patients].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {38}, number = {7}, pages = {856-860}, pmid = {33168499}, issn = {1673-4254}, abstract = {OBJECTIVE: To analyze the characteristics of abnormal granulocytic differentiation in breast cancer patients and explore the role of TGF-β1 in granulocytic differentiation of hematopoietic stem cells (HSCs) and tumor development.

METHODS: Blood samples were collected from 52 patients with invasive ductal carcinoma and 47 healthy donors. The distribution of granulocytes was compared between the two groups and the effects of surgery and radiotherapy on granulocytes were analyzed. The relationship between granulocyte abnormalities and the clinicopathological characteristics of the patients was analyzed. Spleen hematopoietic stem cells isolated from normal and tumor-bearing mice were cultured and treated with TGF-β1, and colony formation of the myeloid cells was compared and the proportion of granulocytes was analyzed with flow cytometry.

RESULTS: The white blood cell (WBC) count, neutrophils, total granulocytes, granulocyte ratio in the total WBCs, and neutrophil/lymphocyte ratio (NLR) were significantly increased (P < 0.05), while the eosinophils and its subpopulations were obviously decreased (P < 0.05) in breast cancer patients. Clone formation experiments showed that the numbers of CFU-GM, BFU-E and CFU-M colonies were significantly greater in the spleen cells from tumor-bearing mice than in those from normal mice (P < 0.05). TGF- β1 treatment obviously suppressed clone formation in spleen HSCs from normal mice but significantly promoted the proliferation and granulocyte differentiation of the spleen HSCs from tumor-bearing mice.

CONCLUSIONS: Breast cancer patients have obvious abnormalities in granulocytic differentiation possibly as a result of hematopoietic stem cell differentiation imbalance induced by TGF-β1 and other growth factors produced by the tumor cells. TGF-β1 highlights a paradoxical shift in the regulation of clone formation and granulocytic differentiation of spleen hematopoietic stem cells.}, } @article {pmid32550335, year = {2019}, author = {Pülat, H and Sabuncuoğlu, MZ and Karaköse, O and Benzin, MF and Eroğlu, HE and Kemal Kürşat Bozkurt, KKB}, title = {A rare breast tumor: primary neuroendocrine carcinoma.}, journal = {Turkish journal of surgery}, volume = {35}, number = {3}, pages = {236-240}, pmid = {32550335}, issn = {2564-6850}, abstract = {Breast cancer is the most frequently seen cancer in females but primary neuroendocrine carcinoma of the breast, which was defined as a separate entity in the 2003 World Health Organisation tumour classification, is seen extremely rarely. This entity, which is still not well-defined and has not been well-researched, demonstrates a more aggressive course than invasive ductal carcinoma. As metastatic breast neuroendocrine tumours are more widespread and the treatment strategy is different, preoperative differential diagnosis is important. The basic diagnostic method is pathological examination. If a neuroendocrine pattern is determined in microscopy, then immunohistochemical study of neuroendocrine markers should be made. It is necessary to be vigilant in terms of synchronous tumours and metachronous tumours which may develop in the postoperative period as the incidence of synchronous and metachronous cancers in patients with neuroendocrine tumours is higher compared to the general population. The case presented here is of a 73-year old patient who presented with complaints of a breast lump, which was thought to be invasive breast cancer, and as a result of the operation with pathological and immunohistochemical examination, primary neuroendocrine carcinoma of the breast was determined. With more advanced evaluations, no synchronous or metachronous tumours were determined.}, } @article {pmid32688833, year = {2008}, author = {Müller, J and Braune, H and Diepenbrock, W}, title = {Photosynthesis-stomatal conductance model LEAFC3-N: specification for barley, generalised nitrogen relations, and aspects of model application.}, journal = {Functional plant biology : FPB}, volume = {35}, number = {10}, pages = {797-810}, doi = {10.1071/FP08088}, pmid = {32688833}, issn = {1445-4416}, abstract = {We discuss a generalised formulation of the nitrogen-sensitive photosynthesis-stomatal conductance model LEAFC3-N to be used as a submodel of functional-structural plant models (FSPMs) or traditional crop growth models for C3-crops. Based on a parameterisation study for barley, we demonstrate that the large variation of characteristics related to potential leaf photosynthesis and stomatal conductance, along with different factors, can be accounted for by introducing functions that relate parameter values to nitrogen contents. These relationships follow the same pattern for different C3 crops, and their parameters are in close range. The accuracy of the parameters and the minimum simulation time step required for reliable predictions of the integrated diurnal carbon gain (IDC) is assessed. For IDC predictions with an accuracy of about ±5%, the accuracy of the slope of the relationship between maximum carboxylation rate and leaf nitrogen content should be of similar order. For other key model parameters, an error of ±20% or even greater may be tolerated. A time step of 1-2 h will be sufficient to predict IDC with an accuracy of about ±5%.}, } @article {pmid32341588, year = {2020}, author = {Isozaki, H and Yamamoto, Y and Sakai, K and Sho, T and Ishihara, K and Murakami, S and Matsumoto, S and Takama, T}, title = {Mucinous Carcinoma of the Breast: Clinicopathological Features and Long-term Prognosis in Comparison with Invasive Ductal Cancer; A Single Hospital's 30+-Year Experience.}, journal = {Acta medica Okayama}, volume = {74}, number = {2}, pages = {137-143}, doi = {10.18926/AMO/58272}, pmid = {32341588}, issn = {0386-300X}, mesh = {Adenocarcinoma, Mucinous/*mortality/pathology/therapy ; Adult ; Aged ; Breast Neoplasms/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Progression-Free Survival ; Proportional Hazards Models ; }, abstract = {Mucinous carcinoma (MC) of the breast is a rare and special type of malignancy, with a substantial amount of extracellular mucin. We compared the clinicopathological features and the long-term survival of MC patients with those of invasive ductal carcinoma-no special type (IDC-NST) patients, and we examined prognostic factors of MC. A total of 116 patients with mucinous carcinoma and 3,258 patients with IDC-NST who underwent surgery at our hospital (1977-2008) were enrolled. The 10-year overall survival rate and breast cancer-specific survival rate (BSS) of the MC patients (88.3%, 93.7%) were both significantly higher than those of IDC-NST patients (81.6%, 85.0%) (p=0.015, p=0.005, respectively). A Cox regression analysis demonstrated that MC tended to be an independent prognostic factor (hazard ratio 0.44, p=0.098). The BSS of the MC patients with positive lymph node (LN) metastasis was significantly poorer than that of the patients without it, by univariate analysis (p=0.002). The tumor size in the MC patients with positive LN metastasis (mean 3.2 cm) was significantly larger than that in the patients without it (mean 1.9 cm) (p=0.0004). Although a Cox regression analysis revealed no independent factor, MC patients with positive LN metastasis should be treated for advanced invasive ductal breast cancer.}, } @article {pmid32341397, year = {2020}, author = {Cai, L and Tong, Y and Zhu, X and Shen, K and Zhu, J and Chen, X}, title = {Prolonged Time to Adjuvant Chemotherapy Initiation Was Associated with Worse Disease Outcome in Triple Negative Breast Cancer Patients.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {7029}, pmid = {32341397}, issn = {2045-2322}, mesh = {Animals ; Cats ; *Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/metabolism ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; Triple Negative Breast Neoplasms/*drug therapy/metabolism/pathology ; }, abstract = {The optimal time to adjuvant chemotherapy (TTC) for breast cancer (BC) patients remains uncertain. Herein, we aim to evaluate the association between TTC and prognosis among different subtypes in modern era of adjuvant chemotherapy. BC patients receiving operation and adjuvant chemotherapy between January 2009 and December 2015 were included. Enrolled patients were categorized into TTC ≤4 weeks and >4 weeks groups. Relapse-free survival (RFS) and overall survival (OS) were compared according to TTC and analyzed among different BC molecular subtypes. A total of 2611 patients were included. Elder age (P = 0.005), more comorbidities (P <0.001), breast-conserving surgery (P = 0.001), non-invasive ductal carcinoma (P = 0.012), and HER2-positivity (P <0.001) were associated with prolonged TTC. Among whole BC population, no significant difference was observed between two TTC groups in terms of RFS (P = 0.225) or OS (P = 0.355). However, for triple negative (TNBC) patients, TTC >4 weeks was independently related with worse RFS (5-year RFS 81.9% vs 89.3%; HR, 1.89; 95% CI, 1.09 to 3.27; P = 0.024) and OS (5-year OS 84.0% vs 94.0%; HR, 2.49; 95% CI, 1.30 to 4.76; P = 0.006) compared with those TTC ≤4 weeks. Prolonged TTC >4 weeks after BC surgery was not associated with worse survival outcomes in the whole BC patients. However, TTC >4 weeks may increase risk of relapse or death in TNBC patients, which deserves further clinical evaluation.}, } @article {pmid32338774, year = {2020}, author = {Kumar, V and Agrawal, R and Pandey, A and Kopf, S and Hoeffgen, M and Kaymak, S and Bandapalli, OR and Gorbunova, V and Seluanov, A and Mall, MA and Herzig, S and Nawroth, PP}, title = {Compromised DNA repair is responsible for diabetes-associated fibrosis.}, journal = {The EMBO journal}, volume = {39}, number = {11}, pages = {e103477}, pmid = {32338774}, issn = {1460-2075}, support = {R37 AG046320/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; //Helmholtz Cross Program Topic Metabolic Dysfunction/ ; //Foundation for Diabetes Research/ ; GRK 1874-DIAMICOM//Deutsche Forschungsgemeinschaft (DFG)/ ; R01 AG027237/AG/NIA NIH HHS/United States ; P01 AG051449/AG/NIA NIH HHS/United States ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {A549 Cells ; *DNA End-Joining Repair ; Diabetes Mellitus, Type 1/genetics/*metabolism/pathology ; Diabetes Mellitus, Type 2/genetics/*metabolism/pathology ; Fibrosis ; HEK293 Cells ; Humans ; }, abstract = {Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD[+] /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes.}, } @article {pmid32334972, year = {2020}, author = {Dickens, CE and Safer, DL and Runfola, CD and Gibbs, EL and Welch, H and Sadeh-Sharvit, S}, title = {The offspring of parents undergoing a weight loss surgery: a systematic review.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {16}, number = {6}, pages = {806-815}, doi = {10.1016/j.soard.2020.02.006}, pmid = {32334972}, issn = {1878-7533}, mesh = {*Bariatric Surgery ; Child ; Feeding Behavior ; Humans ; Obesity ; *Parents ; }, abstract = {The offspring of parents with obesity are at an increased risk of developing this condition themselves because of genetic and environmental factors. One subgroup that may be at particularly high risk of developing obesity is the offspring of parents who have undergone weight loss surgery (PWLS). To date, little research has focused on these offspring or their parents. This systematic review addresses this gap by integrating available literature and assessing the quality of the evidence. To be included, studies were required to have researched characteristics of the offspring of PWLS or parental feeding practices within this population. After review, 12 studies met inclusion criteria. Findings include evidence for heightened risk of obesity among children of PWLS. However, research suggests these children may experience positive, although time-limited, health outcomes after their parents' surgeries. Quality of the evidence was rated as low, primarily because of the lack of randomized controlled studies and information regarding available interventions specifically targeting this vulnerable population. This review underscores the need for research to improve understanding of PWLS families to better support them and capitalize on postbariatric surgery benefits.}, } @article {pmid32328154, year = {2020}, author = {Yuan, G and Liu, Y and Huang, W and Hu, B}, title = {Differentiating Grade in Breast Invasive Ductal Carcinoma Using Texture Analysis of MRI.}, journal = {Computational and mathematical methods in medicine}, volume = {2020}, number = {}, pages = {6913418}, pmid = {32328154}, issn = {1748-6718}, mesh = {Algorithms ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Computational Biology ; Diagnosis, Computer-Assisted/methods/statistics & numerical data ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods/statistics & numerical data ; Machine Learning ; Magnetic Resonance Imaging/*methods/statistics & numerical data ; Models, Statistical ; Neoplasm Grading/*methods/statistics & numerical data ; Neural Networks, Computer ; Support Vector Machine ; Wavelet Analysis ; }, abstract = {PURPOSE: The objective of this study is to investigate the use of texture analysis (TA) of magnetic resonance image (MRI) enhanced scan and machine learning methods for distinguishing different grades in breast invasive ductal carcinoma (IDC). Preoperative prediction of the grade of IDC can provide reference for different clinical treatments, so it has important practice values in clinic.

METHODS: Firstly, a breast cancer segmentation model based on discrete wavelet transform (DWT) and K-means algorithm is proposed. Secondly, TA was performed and the Gabor wavelet analysis is used to extract the texture feature of an MRI tumor. Then, according to the distance relationship between the features, key features are sorted and feature subsets are selected. Finally, the feature subset is classified by using a support vector machine and adjusted parameters to achieve the best classification effect.

RESULTS: By selecting key features for classification prediction, the classification accuracy of the classification model can reach 81.33%. 3-, 4-, and 5-fold cross-validation of the prediction accuracy of the support vector machine model is 77.79%~81.94%.

CONCLUSION: The pathological grading of IDC can be predicted and evaluated by texture analysis and feature extraction of breast tumors. This method can provide much valuable information for doctors' clinical diagnosis. With further development, the model demonstrates high potential for practical clinical use.}, } @article {pmid32318510, year = {2020}, author = {Shahid, M and Schroeder, M and Radigan, K and Zamulko, AO}, title = {Asymptomatic cervical stiffness as the sole presenting feature of ovarian follicular lymphoma: The value of hands-on medicine.}, journal = {Journal of family medicine and primary care}, volume = {9}, number = {2}, pages = {1260-1262}, pmid = {32318510}, issn = {2249-4863}, abstract = {A primary care visit is the first encounter of a patient with health care. In context to malignancies, breast cancer and primary ovarian lymphomas are NA clinically and morphologically different malignancies. The rare concurrence of breast cancer and non-Hodgkin lymphoma (NHL) does not warrant any routine surveillance through testing but we present a case of a 71-year-old female with the history of invasive ductal carcinoma of the breast in remission who was diagnosed with follicular carcinoma after an abnormal pelvic examination during her routine primary care visit. This highlights that a routine PC visit with a skilled physical examination can prove to be one of the most cost-effective tools for screening high-risk cancer patients in remission.}, } @article {pmid32317515, year = {2020}, author = {Pyla, RD and Potekar, RM and Patil, VS and Reddy, AK and Sathyashree, KV}, title = {Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {2}, pages = {200-204}, doi = {10.4103/IJPM.IJPM_155_19}, pmid = {32317515}, issn = {0974-5130}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Mast Cells/immunology/*pathology ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Microenvironment/*immunology ; }, abstract = {CONTEXT: Breast cancer constitutes nearly one third of cancers among women. Immune responses caused by neoplastic cells lead to the accumulation of inflammatory cells like mast cells (MCs), macrophages, lymphocytes, and plasma cells around the tumor tissue forming the tumor microenvironment.

AIM: The study aims at quantifying the role of MCs in different grades of invasive carcinoma of breast with respect to estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2/neu).

MATERIALS AND METHODS: This study included 60 cases of invasive carcinoma of breast. Toluidine blue staining was used for quantitative MC analysis and correlated with immunohistochemistry analysis for hormonal markers' positivity-ER, PR and HER2/neu.

RESULTS: The mean age was 52 years (range: 25-75 years). The average number of MCs in Grade I, II, and III were 24.05, 18.4, and 7.9, respectively, with a significant P value. ER, PR, and HER2/neu positivity was found in 60%, 55%, and 32% of the cases, respectively. ER positivity with mean MC count of 23.55 was found in 36 cases, and 33 cases were positive for PR with a mean MC count of 24.18 and a significant P value. HER2 positive cases were 28 with a mean MC count of 20.82.

CONCLUSION: The presence of MCs in breast cancer is inversely proportional to the grade of tumor, i.e., a maximum number of MCs were seen in low grade tumors. In addition, there is a positive correlation between ER and PR receptor positivity with the presence of MCs in the stroma of breast cancer.}, } @article {pmid32315112, year = {2020}, author = {Mannaerts, CK and Engelbrecht, MRW and Postema, AW and van Kollenburg, RAA and Hoeks, CMA and Savci-Heijink, CD and Van Sloun, RJG and Wildeboer, RR and De Reijke, TM and Mischi, M and Wijkstra, H}, title = {Detection of clinically significant prostate cancer in biopsy-naïve men: direct comparison of systematic biopsy, multiparametric MRI- and contrast-ultrasound-dispersion imaging-targeted biopsy.}, journal = {BJU international}, volume = {126}, number = {4}, pages = {481-493}, doi = {10.1111/bju.15093}, pmid = {32315112}, issn = {1464-410X}, support = {UVA 2013-5941//KWF Kankerbestrijding/International ; }, mesh = {Aged ; Contrast Media ; Humans ; *Image-Guided Biopsy ; Male ; Middle Aged ; *Multiparametric Magnetic Resonance Imaging ; Neoplasm Grading ; Prospective Studies ; Prostatic Neoplasms/*diagnostic imaging/*pathology ; Sensitivity and Specificity ; *Ultrasonography ; }, abstract = {OBJECTIVES: To compare and evaluate a multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) strategy, contrast-ultrasound-dispersion imaging (CUDI)-TBx strategy and systematic biopsy (SBx) strategy for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve men.

PATIENTS AND METHODS: A prospective, single-centre paired diagnostic study included 150 biopsy-naïve men, from November 2015 to November 2018. All men underwent pre-biopsy mpMRI and CUDI followed by a 12-core SBx taken by an operator blinded from the imaging results. Men with suspicious lesions on mpMRI and/or CUDI also underwent MRI-TRUS fusion-TBx and/or cognitive CUDI-TBx after SBx by a second operator. A non-inferiority analysis of the mpMRI- and CUDI-TBx strategies in comparison with SBx for International Society of Urological Pathology Grade Group [GG] ≥2 PCa in any core with a non-inferiority margin of 1 percentage point was performed. Additional analyses for GG ≥2 PCa with cribriform growth pattern and/or intraductal carcinoma (CR/IDC), and GG ≥3 PCa were performed. Differences in detection rates were tested using McNemar's test with adjusted Wald confidence intervals.

RESULTS: After enrolment of 150 men, an interim analysis was performed. Both the mpMRI- and CUDI-TBx strategies were inferior to SBx for GG ≥2 PCa detection and the study was stopped. SBx found significantly more GG ≥2 PCa: 39% (56/142), as compared with 29% (41/142) and 28% (40/142) for mpMRI-TBx and CUDI-TBx, respectively (P < 0.05). SBx found significantly more GG = 1 PCa: 14% (20/142) compared to 1% (two of 142) and 3% (four of 142) with mpMRI-TBx and CUDI-TBx, respectively (P < 0.05). Detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa did not differ significantly between the strategies. The mpMRI- and CUDI-TBx strategies were comparable in detection but the mpMRI-TBx strategy had less false-positive findings (18% vs 53%).

CONCLUSIONS: In our study in biopsy-naïve men, the mpMRI- and CUDI-TBx strategies had comparable PCa detection rates, but the mpMRI-TBX strategy had the least false-positive findings. Both strategies were inferior to SBx for the detection of GG ≥2 PCa, despite reduced detection of insignificant GG = 1 PCa. Both strategies did not significantly differ from SBx for the detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa.}, } @article {pmid32310154, year = {2020}, author = {Suhani, S and Kazi, M and Parshad, R and Seenu, V and Verma, E and Mathur, S and Gupta, SD and Haresh, KP}, title = {An audit of over 1000 breast cancer patients from a tertiary care center of Northern India.}, journal = {Breast disease}, volume = {39}, number = {2}, pages = {91-99}, doi = {10.3233/BD-190435}, pmid = {32310154}, issn = {1558-1551}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/physiopathology ; Breast Neoplasms, Male/*epidemiology/physiopathology ; Female ; Humans ; India/epidemiology ; Male ; *Medical Audit ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers/*statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the commonest cancer among women. India along with United States and China collectively account for one third of the global burden. The present study reports the clinico-epidemiological data of our patient population. This may help in better understanding of the disease in our population and also form ground for conducting further breast cancer research in India.

METHODS: The study was conducted at an apex teaching and medical research institution in India from September 2013 to April 2015 as a retrospective review of prospectively collected data of breast cancer patients. The socio-demographic characteristics, reproductive risk factors, clinical presentation, TNM staging and histopathological characteristics for breast cancer in these patients were recorded. The data was recorded on an Xcel spreadsheet and analyzed using IBM SPSS 21.

RESULTS: The study comprised of 1310 breast cancer patients with males comprising 1.1%. The median age of presentation was 47 years, and menarche 14 years. Most of women were married and multiparous. More than half of the women were postmenopausal at presentation. All patients were symptomatic at presentation with median duration of symptom of 5 months and median lump size of 5 cm. Most common stage at presentation was Stage II and most common histopathology was Invasive ductal carcinoma. 61.9% tumors were hormone receptor positive. Triple negative cancers formed one third of all tumors.

CONCLUSION: Breast cancer in the Indian scenario is a disease of younger woman who lack the characteristic reproductive and demographic risk factors. This calls for a need to study the clinico-demographic risk factors and characteristics of our own population.}, } @article {pmid32307272, year = {2021}, author = {Girometti, R and Sardanelli, F and Marconi, V and Bondini, F and De Serio, I and Bracciani, A and Londero, V and Zuiani, C}, title = {Diagnostic Performance of Digital Breast Tomosynthesis, Unenhanced MRI, and Their Combination in the Preoperative Assessment of Breast Cancer: A Multi-reader Study.}, journal = {Academic radiology}, volume = {28}, number = {10}, pages = {1339-1351}, doi = {10.1016/j.acra.2020.03.018}, pmid = {32307272}, issn = {1878-4046}, mesh = {*Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: To compare the diagnostic performance of digital breast tomosynthesis (DBT) and unenhanced magnetic resonance imaging (UMRI) in the preoperative assessment of breast cancer.

MATERIALS AND METHODS: We retrospectively included 59 patients with 74 pathology-proven cancers who underwent DBT and preoperative 1.5 T magnetic resonance imaging between January 2016 and February 2017. Four residents with 2-3 years of experience, blinded to pathology, independently reviewed DBT and UMRI (diffusion-weighted and unenhanced T1-weighted sequences), using the breast imaging reporting and data system (BI-RADS) and a 0-5 Likert score, respectively. We calculated per-lesion sensitivity and positive predictive value of DBT, UMRI, and combined DBT+UMRI, as well as the agreement between DBT and UMRI vs. pathology in assessing cancer size (Bland-Altman analysis). Logistic regression was performed to assess clinical features predictive of missing cancer.

RESULTS: Of 74 lesions, 84% were invasive ductal carcinoma, 27% of which with an in situ component; 31% of cancers were ≤10 mm large. Sensitivity of UMRI (74-85%) was equal or higher than that of DBT (68-82%), with similar positive predictive value (93-97% vs. 98-100%, respectively). DBT+UMRI increased the sensitivity up to 88%. UMRI showed closer limits of agreement with pathological size than DBT. Missing cancer was independently predicted by size ≤10 mm on DBT, UMRI, and DBT+UMRI (odds ratio 18.7, 5.1, and 13.3, respectively), and by increased breast density on DBT alone (odds ratio 3.50).

CONCLUSION: UMRI was equal or better than DBT in the preoperative assessment of breast cancer. Combined imaging achieved up to 88% per-lesion sensitivity, suggesting potential use in clinical practice.}, } @article {pmid32299754, year = {2020}, author = {El Abbass, KA and Abdellateif, MS and Gawish, AM and Zekri, AN and Malash, I and Bahnassy, AA}, title = {The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer.}, journal = {Clinical breast cancer}, volume = {20}, number = {4}, pages = {e373-e384}, doi = {10.1016/j.clbc.2019.11.008}, pmid = {32299754}, issn = {1938-0666}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*genetics/secondary/therapy ; Case-Control Studies ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Healthy Volunteers ; Humans ; Middle Aged ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; Primary Cell Culture ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Cells, Cultured ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).

METHODS: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.

RESULTS: The number of CD44[+]CD24[-/low] cells associated significantly at the end of culture with the expression level of Wnt, β-catenin, and distant metastasis (P < .001, P = .015 and P = .003, respectively). There was significant association between the mammosphere number and CD44[+]CD24[-/low] cells as well as AKT expression (P = .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P < .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P = .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P < .001, P = .001, P = .014, respectively).

CONCLUSION: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.}, } @article {pmid32291826, year = {2020}, author = {Cairns, C and Greenwalt, I and Fan, KL and Willey, SC}, title = {Contralateral axillary sentinel lymph node in breast cancer recurrence.}, journal = {The breast journal}, volume = {26}, number = {7}, pages = {1379-1381}, doi = {10.1111/tbj.13816}, pmid = {32291826}, issn = {1524-4741}, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging/surgery ; Female ; Humans ; Lymph Nodes/diagnostic imaging/surgery ; Neoplasm Recurrence, Local/diagnostic imaging/surgery ; *Sentinel Lymph Node/diagnostic imaging/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {The rare but significant reports of aberrant lymph node drainage outside of the ipsilateral axilla in patients with breast cancer necessitate a review of the staging and treatment strategies for these patients. Current staging modalities continue to describe this phenomenon as a stage IV cancer, which could have profound implications for clinical management. We report a case of a patient with recurrent right breast invasive ductal carcinoma whose preoperative lymphoscintigraphy revealed sentinel lymph node drainage to the contralateral axilla. This discovery subsequently altered surgical planning and her ultimate stage.}, } @article {pmid32285374, year = {2020}, author = {Davey, MG and Brennan, M and Ryan, ÉJ and Corbett, M and Abd Elwahab, S and Walsh, S and McLaughlin, RJ}, title = {Defining clinicopathological and radiological features of breast cancer in women under the age of 35: an epidemiological study.}, journal = {Irish journal of medical science}, volume = {189}, number = {4}, pages = {1195-1202}, doi = {10.1007/s11845-020-02229-z}, pmid = {32285374}, issn = {1863-4362}, mesh = {Adult ; Breast Neoplasms/pathology/*radiotherapy ; Epidemiologic Studies ; Female ; Humans ; Retrospective Studies ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the most commonly diagnosed female cancer. Diagnosis in younger women (under 35 years) is different to their older counterparts, and mammography is not considered as sensitive in this cohort. Consequentially, younger patients may present later with more advanced disease.

METHODS: This is a retrospective analysis of a prospectively updated database containing consecutive patients who presented to the symptomatic breast unit of Galway University Hospital between 2009 and 2015. Patient clinicopathologic factors, clinical examination features, diagnostic radiological modalities and Bi-RADS score were all assessed. Data was analysed using Statistical Package for the Social Sciences version 25.

RESULTS: One thousand eight hundred thirty-six patients were diagnosed with breast cancer, and of these, 51 (2.8%) patients were < 35 years. Invasive ductal carcinoma made up 90% of diagnosis, and 42% had an associated ductal carcinoma in situ. Fifty-four percent were high-grade tumours and 52% presented with stage III disease or greater. The main radiological tool used was ultrasound, which had a sensitivity of 87.50% (95% confidence interval [CI] 74.75 to 95.27%). Mammogram sensitivity was 86.84% (95% CI 71.91 to 95.59%). Magnetic resonance imaging was used in 29% of cases, with a sensitivity of 100.00% (95% CI 78.20 to 100.00%).

CONCLUSION: Females under 35 tend to be diagnosed with aggressive, advanced stage tumours. Ultrasound remains the radiological test of choice, although diagnosis using mammography demonstrated a relatively high sensitivity compared with previous reports. This study emphasises the varying epidemiology of breast cancer in younger patients and the potential role of mammography in making radiological diagnosis in those who are symptomatic.}, } @article {pmid32283624, year = {2020}, author = {Krasovsky, T and Weiss, PL and Zuckerman, O and Bar, A and Keren-Capelovitch, T and Friedman, J}, title = {DataSpoon: Validation of an Instrumented Spoon for Assessment of Self-Feeding.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {7}, pages = {}, pmid = {32283624}, issn = {1424-8220}, support = {1716/12//Israeli Centers for Research Excellence/ ; }, mesh = {Adult ; Biomechanical Phenomena ; *Eating ; Female ; Humans ; Male ; *Mobile Applications ; Movement ; Robotics ; Young Adult ; }, abstract = {Clinically feasible assessment of self-feeding is important for adults and children with motor impairments such as stroke or cerebral palsy. However, no validated assessment tool for self-feeding kinematics exists. This work presents an initial validation of an instrumented spoon (DataSpoon) developed as an evaluation tool for self-feeding kinematics. Ten young, healthy adults (three male; age 27.2 ± 6.6 years) used DataSpoon at three movement speeds (slow, comfortable, fast) and with three different grips: "natural", power and rotated power grip. Movement kinematics were recorded concurrently using DataSpoon and a magnetic motion capture system (trakSTAR). Eating events were automatically identified for both systems and kinematic measures were extracted from yaw, pitch and roll (YPR) data as well as from acceleration and tangential velocity profiles. Two-way, mixed model Intraclass correlation coefficients (ICC) and 95% limits of agreement (LOA) were computed to determine agreement between the systems for each kinematic variable. Most variables demonstrated fair to excellent agreement. Agreement for measures of duration, pitch and roll exceeded 0.8 (excellent agreement) for >80% of speed and grip conditions, whereas lower agreement (ICC < 0.46) was measured for tangential velocity and acceleration. A bias of 0.01-0.07 s (95% LOA [-0.54, 0.53] to [-0.63, 0.48]) was calculated for measures of duration. DataSpoon enables automatic detection of self-feeding using simple, affordable movement sensors. Using movement kinematics, variables associated with self-feeding can be identified and aid clinical reasoning for adults and children with motor impairments.}, } @article {pmid32279596, year = {2020}, author = {Duman, B and Kuşman, A and Çolak, B and Şenler, FÇ and Kumbasar, H}, title = {Tamoxifen-induced acute mania: A case report.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {26}, number = {8}, pages = {2025-2027}, doi = {10.1177/1078155220915959}, pmid = {32279596}, issn = {1477-092X}, mesh = {Acute Disease ; Antineoplastic Agents, Hormonal/*adverse effects ; Breast Neoplasms/*drug therapy ; Female ; Humans ; Mania/*chemically induced ; Middle Aged ; Tamoxifen/*adverse effects ; }, abstract = {INTRODUCTION: Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.

CASE REPORT: A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21 days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.

MANAGEMENT AND OUTCOME: The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24 h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.

DISCUSSION: To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen's nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.}, } @article {pmid32272928, year = {2020}, author = {Sutham, K and Khuwuthyakorn, P and Thinnukool, O}, title = {Thailand medical mobile application for patients triage base on criteria based dispatch protocol.}, journal = {BMC medical informatics and decision making}, volume = {20}, number = {1}, pages = {66}, pmid = {32272928}, issn = {1472-6947}, mesh = {*Emergency Medical Services ; Humans ; *Mobile Applications ; Patients ; Reproducibility of Results ; Retrospective Studies ; Thailand ; Triage ; }, abstract = {BACKGROUND: Before patients are admitted into the emergency department, it is important to undertake a pre-hospital process, both in terms of treatment performance and a request for resources from an emergency unit. The existing system to triage patients in Thailand is not functioning to its full capacity in either the primary medical system or pre-hospital treatment with shortcomings in the areas of speed, features, and appropriate systems. There is a high possibility of issuing a false Initial Dispatch Code (IDC), which will cause the over or underutilisation of emergency resources, such as rescue teams, community hospitals and emergency medical volunteers.

METHODS: A usability system design, together with a reliability test, was applied to develop an application to optimise the pre-hospital process, specifically to sort patients, using an IDC to improve the request for emergency resources. The triage mobile application was developed on both iOS and Android operating systems to support patient triage based on Criteria Based Dispatch (CBD). The 25 main symptom categories covered by CBD were used to design and develop the application, and 12 emergency medical staff, including doctors and nurses, were asked to test the system in the aspects of triage protocol correction, triage reliability, usability and user satisfaction.

RESULTS: The results of testing the proposed triage application were compared with the time used to triage by experienced staff and it was found that, in non-trauma cases, it was faster and more effective to use the application for emergency operations and to correct the IDC code representation.

CONCLUSIONS: The triage application will be utilised to support the pre-hospital process and to classify patients' conditions before they are admitted to the Emergency Department (ED). The application is suitable for users who are not medical emergency staff. Patients with non-trauma symptoms may be a suitable group to use the application in terms of time used to identify IDC for their own symptoms. The use of the application can be beneficial for those who wish to self-identify their symptoms before requesting medical services.}, } @article {pmid32272126, year = {2020}, author = {Yirmiya, K and Motsan, S and Zagoory-Sharon, O and Feldman, R}, title = {Human attachment triggers different social buffering mechanisms under high and low early life stress rearing.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {152}, number = {}, pages = {72-80}, doi = {10.1016/j.ijpsycho.2020.04.001}, pmid = {32272126}, issn = {1872-7697}, mesh = {Adolescent ; Child ; *Child Rearing ; Child, Preschool ; Female ; Humans ; Hydrocortisone/*metabolism ; Longitudinal Studies ; Male ; Maternal Behavior/*physiology ; *Mother-Child Relations ; *Object Attachment ; Oxytocin/*metabolism ; *Safety ; *Social Behavior ; Stress, Psychological/metabolism/*physiopathology ; }, abstract = {Social buffering - the attenuation of stress by maternal safety signals - is a core mammalian-general stress management mechanism implicating two ancient systems: the oxytocinergic and HPA systems. Yet, because human attachments are representation-based, understanding social buffering mechanisms in humans requires the assessment of relationship history and consideration of early life stress (ELS), which alters stress responsivity. We followed a unique trauma-exposed cohort across childhood, versus a low-stress control group, and repeatedly observed maternal sensitive, safety-promoting style. In adolescence, we used an attachment induction paradigm that exposed children to both live and reminders of attachment safety signals and measured oxytocin and cortisol baseline and response, to test how maternal safety signals impact hormonal reactivity in children reared under high- versus low-stress conditions. Only safety-promoting mothers exhibited a stress-buffering function, but their effect was system-specific and depended on the rearing context. For oxytocin, safety-promoting mothers normalized the deficient baseline oxytocin levels observed in ELS youth by implicating a plasticity-by-affiliation mechanism. For cortisol, safety-promoting mothering reduced the initial stress response only among youth reared in low-stress contexts via the typical buffering-by-safety mechanism. Results suggest that human attachments require internalized security evolving over time to trigger a stress buffering function. Under conditions of chronic early stress, the stressful rearing context overrides the maternal safety signals, normative stress buffering mechanisms fail, and safety-promoting mothers switch to an immature, affiliation-based mechanism that relies on maternal presence.}, } @article {pmid32271809, year = {2020}, author = {Lee, SB and Bose, S and Ahn, SH and Son, BH and Ko, BS and Kim, HJ and Chung, IY and Kim, J and Lee, W and Ko, MS and Lee, K and Chang, S and Park, HS and Lee, JW and Kim, DC}, title = {Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0231004}, pmid = {32271809}, issn = {1932-6203}, mesh = {Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*diagnosis/pathology ; Carcinoma, Ductal, Breast/blood/diagnosis ; Case-Control Studies ; Female ; Glycosylation ; Humans ; Polysaccharides/*blood ; ROC Curve ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest's software "NosIDsys." BrC-associated "NosID" N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917-0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.}, } @article {pmid32269189, year = {2020}, author = {Lee, YH and Kwon, MJ and Park, JH and Jeong, SJ and Kim, TH and Jeong, HW and Lee, SH}, title = {Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {13}, pages = {1665-1669}, pmid = {32269189}, issn = {1349-7235}, mesh = {Adrenal Gland Neoplasms/*complications/surgery ; Adrenalectomy ; Adult ; Biopsy ; Breast Neoplasms/*complications/therapy ; Cafe-au-Lait Spots/pathology ; Female ; Humans ; Incidental Findings ; Neurofibromatosis 1/*complications ; Pheochromocytoma/*complications ; Skin Neoplasms/pathology ; }, abstract = {A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.}, } @article {pmid32266539, year = {2020}, author = {Schmidt, G and Solomayer, EF and Bohle, RM and Gerlinger, C and Radosa, JC and Endrikat, J and Kasoha, M}, title = {Is vimentin a potential prognostic factor for patients with triple-negative breast cancer?.}, journal = {Journal of cancer research and clinical oncology}, volume = {146}, number = {8}, pages = {2109-2116}, pmid = {32266539}, issn = {1432-1335}, mesh = {Biomarkers, Tumor/biosynthesis ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Tissue Array Analysis ; Triple Negative Breast Neoplasms/*metabolism/pathology ; Vimentin/*biosynthesis ; }, abstract = {OBJECTIVE: To evaluate the prognostic potential of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 in patients with triple-negative breast cancer (TNBC).

MATERIAL AND METHODS: Tumor specimens of 60 patients with histologically confirmed TNBC were retrospectively analyzed. Formalin-fixed paraffin-embedded blocks of the tumor tissue were used to prepare tissue microarrays (TMAs). After immune-histochemical staining, protein expression of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 was determined and the immunoreactive score (IRS) was calculated. The protein expression was correlated to overall (OS) and disease-free survival (DFS).

RESULTS: Ninety percent of patients suffered from an invasive ductal carcinoma T1 or T2, 66.7% were N0, and 70% had a G3 tumor with Ki67 of > 14%. Vimentin expression was found in 28/60 patients (46.7%), p53 expression in 30/60 patients (50%), and EGFR expression in 3/60 patients (5%). CK5/6, CK14, and CK17 expression was found in 60.0%, 63.3%, and 66.7%, respectively. Vimentin expression vs no expression was associated with significantly higher mean Ki67 values (52.5% vs. 31.1%; p = 0.0013) and significantly higher p53 expression (67.9% vs. 34.4%; p = 0.0097). No significant association between vimentin expression and OS (p = 0.7710) or DFS (p = 0.5558) was found during a mean follow-up of 92 months.

CONCLUSION: None of the six proteins proved to be suitable prognostic factors for OS and DSF in patients with TNBC.}, } @article {pmid32266446, year = {2020}, author = {Zong, L and Mo, S and Yu, S and Zhou, Y and Zhang, M and Chen, J and Xiang, Y}, title = {Expression of the immune checkpoint VISTA in breast cancer.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {69}, number = {8}, pages = {1437-1446}, doi = {10.1007/s00262-020-02554-3}, pmid = {32266446}, issn = {1432-0851}, support = {81672648//National Natural Science Foundation of China/International ; 81971475//National Natural Science Foundation of China/International ; CAMS-2017-I2M-1-002//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; CAMS-2016-I2M-1-001//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; B7 Antigens/*metabolism ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*metabolism ; Survival Rate ; }, abstract = {V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.}, } @article {pmid32264755, year = {2020}, author = {Porat, R and Erel, L and Pnueli, V and Halperin, E}, title = {Developing ReApp: an emotion regulation mobile intervention for intergroup conflict.}, journal = {Cognition & emotion}, volume = {34}, number = {7}, pages = {1326-1342}, doi = {10.1080/02699931.2020.1747400}, pmid = {32264755}, issn = {1464-0600}, mesh = {Adult ; Aggression ; Anger ; *Emotional Regulation ; Emotions ; Female ; Humans ; Male ; Mobile Applications ; Negotiating/*psychology ; *Video Games ; }, abstract = {People living in areas of intractable conflicts experience extreme negative emotions which ultimately lead to support of aggressive policies. Emotion regulation and particularly cognitive reappraisal has been found to be effective in reducing negative emotional experiences and shifting policy preferences. Therefore, it is important to develop scalable, evidence-based interventions aimed at regulating negative emotions in such contexts. In this paper, we introduce ReApp - a mobile game, aimed at training people to regulate their emotions using cognitive reappraisal. We examine the game's effectiveness in reducing negative emotions and support for aggressive policies in the context of the Israeli-Palestinian conflict. Results indicate that people who played ReApp experienced lower levels of anger and disgust, and were less supportive of aggressive political policies targeted at the outgroup. We believe that games such as ReApp could potentially influence mass audiences and by that promote conflict resolution.}, } @article {pmid32246407, year = {2020}, author = {Padrón, K and Peix, A and Cabrera, L and Garcia, J and Rodriguez, L and Carrillo, R and Mena, E and Fernandez, Y}, title = {Could myocardial viability be related to left ventricular dyssynchrony? Simultaneous evaluation by gated SPECT-MPI.}, journal = {Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology}, volume = {27}, number = {4}, pages = {1158-1167}, pmid = {32246407}, issn = {1532-6551}, mesh = {Aged ; Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography/*methods ; Cardiomyopathy, Dilated/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Myocardial Contraction/*physiology ; Myocardial Ischemia/*physiopathology ; Myocardial Perfusion Imaging/*methods ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: Left ventricular contraction dyssynchrony (LVCD) has been related to induced ischemia and transmural scar but the interplay of myocardial viability and dyssynchrony is unknown. The aim of the present study was to establish the role of dyssynchrony in the context of a viability study performed with nitrate augmentation gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI).

METHODS: Fifty-four consecutive patients with ischemic dilated cardiomyopathy (IDC) and depressed left ventricular ejection fraction (LVEF) were included. They underwent a two-day rest/nitroglycerine (NTG) study GSPECT MPI to determine the myocardial viability. Patients with a nitrate-induced uptake increase of > 10% vs baseline, in at least, two consecutive dysfunctional segments were considered viable as well as those who showed no improvement in the uptake but the uptake was > 50% on post NTG study. Patients with no nitrate-induced uptake increase of > 10% and the uptake of < 50% were considered non-viable. Perfusion, function and LVCD were compared in 25 viable patients vs 29 non-viable patients at baseline and after NTG administration.

RESULTS: After NTG administration, in the viable group, the LVEF increased (36.44 ± 6.64% vs 39.84 ± 6.39%) and the end-systolic volume decreased significantly (119.28 ± 31.77 mL vs 109.08 ± 33.17 mL) (P < 0.01). These patients also experienced a significant reduction in the LVCD variables: phase standard deviation was reduced in the post NTG study (57.77° ± 19.47° vs 52.02° ± 17.09°) as well as the phase histogram bandwidth (190.20° ± 78.83° vs 178.0° ± 76.14°) (P < 0.05). Functional and LVCD variables remained similar in the non-viable patients (P > 0.05).

CONCLUSION: In patients with IDC and depressed LVEF, the myocardial viability detected by rest/ NTG GSPECT MPI, might determine LVCD improvement.}, } @article {pmid32246378, year = {2020}, author = {Le, AN and Harton, J and Desai, H and Powers, J and Zelley, K and Bradbury, AR and Nathanson, KL and Shah, PD and Doucette, A and Freedman, GM and Gabriel, P and Domchek, SM and MacFarland, SP and Maxwell, KN}, title = {Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {1}, pages = {181-188}, pmid = {32246378}, issn = {1573-7217}, support = {K08 CA215312/CA/NCI NIH HHS/United States ; K08CA21531//National Cancer Institute (US)/ ; ITMAT MHB//University of Pennsylvania/ ; 1017184//Burroughs Wellcome Fund/ ; }, mesh = {Adolescent ; Adult ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Female ; Follow-Up Studies ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*complications ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasms, Radiation-Induced/*etiology/pathology ; Prognosis ; Radiotherapy, Adjuvant/*adverse effects ; Retrospective Studies ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.

METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.

RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort.

CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.}, } @article {pmid32245448, year = {2020}, author = {Liu, Z and Li, R and Liang, K and Chen, J and Chen, X and Li, X and Li, R and Zhang, X and Yi, L and Long, W}, title = {Value of digital mammography in predicting lymphovascular invasion of breast cancer.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {274}, pmid = {32245448}, issn = {1471-2407}, support = {81802918//National Natural Science Foundation of China/ ; 2017A4016,2015068//The science and technology planning project of Jiangmen/ ; }, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnostic imaging/*pathology ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mammography/*methods ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Lymphovascular invasion (LVI) has never been revealed by preoperative scans. It is necessary to use digital mammography in predicting LVI in patients with breast cancer preoperatively.

METHODS: Overall 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were enrolled and assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80). Independent t-test and χ2 test were performed.

RESULTS: Difference in Ki-67 between the two groups was statistically significant (P = 0.012). Differences in interstitial edema (P = 0.013) and skin thickening (P = 0.000) were statistically significant between the two groups. Multiple factor analysis showed that there were three independent risk factors for LVI: interstitial edema (odds ratio [OR] = 12.610; 95% confidence interval [CI]: 1.061-149.922; P = 0.045), blurring of subcutaneous fat (OR = 0.081; 95% CI: 0.012-0.645; P = 0.017) and skin thickening (OR = 9.041; 95% CI: 2.553-32.022; P = 0.001).

CONCLUSIONS: Interstitial edema, blurring of subcutaneous fat, and skin thickening are independent risk factors for LVI. The specificity of LVI prediction is as high as 98.8% when the three are used together.}, } @article {pmid32244940, year = {2020}, author = {Özdirik, B and Kayser, A and Ullrich, A and Savic, LJ and Reiss, M and Tacke, F and Wiedenmann, B and Jann, H and Roderburg, C}, title = {Primary Neuroendocrine Neoplasms of the Breast: Case Series and Literature Review.}, journal = {Cancers}, volume = {12}, number = {3}, pages = {}, pmid = {32244940}, issn = {2072-6694}, abstract = {Primary neuroendocrine carcinoma of the breast (NECB) as defined by the World Health Organization (WHO) in 2012 is a rare, but possibly under-diagnosed entity. It is heterogeneous as it entails a wide spectrum of diseases comprising both well-differentiated neuroendocrine tumors of the breast as well as highly aggressive small cell carcinomas. Retrospective screening of hospital charts of 612 patients (2008-2019) from our specialized outpatient unit for neuroendocrine neoplasia revealed five patients diagnosed with NECB. Given the low prevalence of these malignancies, correct diagnosis remains a challenge that requires an interdisciplinary approach. Specifically, NECB may be misclassified as carcinoma of the breast with neuroendocrine differentiation, carcinomas of the breast of no special type/invasive ductal carcinoma, or a metastasis to the breast. Therefore, this study presents multifaceted characteristics as well as the clinical course of these patients and discusses the five cases from our institution in the context of available literature.}, } @article {pmid32244872, year = {2020}, author = {Mikulincer, M and R Shaver, P}, title = {Enhancing the "Broaden and Build" Cycle of Attachment Security in Adulthood: From the Laboratory to Relational Contexts and Societal Systems.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {6}, pages = {}, pmid = {32244872}, issn = {1660-4601}, mesh = {Adult ; Female ; Humans ; Male ; *Marriage ; *Mental Health ; *Object Attachment ; Psychotherapy ; Sexual Partners ; }, abstract = {Attachment theory emphasizes both the importance of the availability of caring, supportive relationship partners, beginning in infancy, for developing a sense of safety and security, and the beneficial effects of this sense of security on psychosocial functioning and physical and mental health. In this article, we briefly review basic concepts of attachment theory, focusing on the core construct of attachment security and present evidence concerning the ways in which this sense can be enhanced in adulthood. Specifically, we review findings from laboratory experiments that have momentarily enhanced the sense of attachment security and examined its effects on emotion regulation, psychological functioning, and prosocial behavior. We then review empirical findings and ideas concerning security enhancement by actual relationship partners, non-human symbolic figures, and societal systems in a wide variety of life domains, such as marital relationships, psychotherapy, education, health and medicine, leadership and management, group interactions, religion, law, and government.}, } @article {pmid32244184, year = {2020}, author = {Schäfer, M and Oeing, CU and Rohm, M and Baysal-Temel, E and Lehmann, LH and Bauer, R and Volz, HC and Boutros, M and Sohn, D and Sticht, C and Gretz, N and Eichelbaum, K and Werner, T and Hirt, MN and Eschenhagen, T and Müller-Decker, K and Strobel, O and Hackert, T and Krijgsveld, J and Katus, HA and Berriel Diaz, M and Backs, J and Herzig, S}, title = {'Corrigendum to "Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia" [Molecular Metabolism 5 (2) (2015) 67-78]'.}, journal = {Molecular metabolism}, volume = {35}, number = {}, pages = {100970}, doi = {10.1016/j.molmet.2020.02.013}, pmid = {32244184}, issn = {2212-8778}, } @article {pmid32242174, year = {2020}, author = {Rasanathan, D and Wang, X}, title = {Trial removal of indwelling urinary catheters in stroke patients: a clinical audit at North Shore Hospital.}, journal = {The New Zealand medical journal}, volume = {133}, number = {1512}, pages = {15-21}, pmid = {32242174}, issn = {1175-8716}, mesh = {*Catheters, Indwelling ; Clinical Audit ; *Device Removal ; Female ; Guideline Adherence ; Hospitals ; Humans ; Male ; New Zealand/epidemiology ; Prospective Studies ; Retrospective Studies ; *Stroke ; *Urinary Catheterization ; Urinary Tract Infections/epidemiology ; }, abstract = {BACKGROUND: This is a baseline clinical audit looking at indwelling urinary catheter (IDC) use and trial removal of catheter (TROC) in stroke patients. We collected data on stroke patients admitted to North Shore Hospital between 26 November 2018-24 May 2019, who underwent insertion of an IDC as an inpatient. A minority of patients had TROC within the recommended guideline period. A high incidence of urinary tract infection (UTI) was found in this patient population. Insufficient documentation and inappropriate indications for IDC insertion were features noted during this audit. Daily electronic reminders and prompting by all members of the rehabilitation team concerning TROC are important to reduce catheter days and reduce UTI rates.

AIMS: To identify if the trial removal of indwelling urinary catheters (TROC) in stroke patients complies with the 2016 American Heart Association/American Stroke Association (AHA/ASA) AHSA guidelines, and to identify any precipitating factors that prevent compliance with the guidelines.

METHODS: We performed a clinical baseline audit that identified patients who were admitted to the acute stroke ward at North Shore Hospital with a diagnosis of stroke from 26 November 2018-24 May 2019 and had an indwelling urinary catheter (IDC) inserted during their admission. The audit consisted of both retrospective and prospective components. Data was collected on patient demographics, the documented indication for IDC insertion, total number of catheter days, the incidence of UTIs and the outcomes after catheter removal.

RESULTS: A total of 49 patients were included. 4.1% of patients had catheters removed within 24 hours (95% confidence interval: 0.011-0.137). The average number of catheter days before removal of IDC was approximately five days. 24.5% of our patient sample went on to develop a urinary tract infection.

CONCLUSIONS: Insufficient documentation and inappropriate indications for IDC insertion were features noted during this audit. Daily electronic reminders and prompting concerning TROC are important to reduce catheter days and reduce infection rates. Indwelling catheters and associated infections impact the length of hospitalisation, mortality and morbidity of stroke patients.}, } @article {pmid32239879, year = {2020}, author = {Zheng, X and Yin, J}, title = {Efficacy of texture analysis in determining the gene amplification status of HER2 2+ for invasive ductal carcinoma cases.}, journal = {Minerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0026-4806.20.06536-2}, pmid = {32239879}, issn = {1827-1669}, abstract = {BACKGROUND: Gene amplification of human epidermal growth factor receptor2 (HER2) 2+ is essential to be determined for treatment planning. A search of the PubMed database indicates that the correlation between texture features from dynamic contrast enhanced (DCE)-MRI and HER2 2+ status has not been investigated extensively in invasive ductal carcinoma cases.

METHODS: 71 DCE-MRI cases of HER2 2+ status verified using fluorescence in situ hybridization (FISH) were selected, including36 positive and 35negative cases. 279 texture features were derived from lesion regions of interest manually drawn onto the subtraction images between pre- and post-contrast agent. Fisher coefficient, mutual information, minimization of both classification error probability and average correlation coefficients as well as a combination of all three methods (MPF) were independently used to reduce the dimensionality of texture parameters. A popular machine learning algorithm, Support Vector Machine, was further applied to determine HER2 2+status. Receiver operating characteristic (ROC) analysis was conducted to evaluate the classification performance.

RESULTS: Diagnostic accuracy was optimal when the most significant discriminatory features were selected using MPF. The area under ROC curve reached 0.863 with corresponding accuracy, sensitivity and specificity rates of 81.80%, 85.71% and 77.78%, respectively.

CONCLUSIONS: Texture analysis based on breast MRI delivered consistently high performance with FISH detection and may serve as a useful supplementary tool for determining the gene amplification status of HER2 2+ for cases with invasive ductal carcinoma.}, } @article {pmid32239352, year = {2020}, author = {Maggi, G and D'Iorio, A and Di Meglio, D and Vinciguerra, A and Amboni, M and Vitale, C and Santangelo, G}, title = {The role of the motor subtypes on the relationship between anxiety and cognitive dysfunctions in Parkinson's disease.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {127}, number = {6}, pages = {893-898}, doi = {10.1007/s00702-020-02179-x}, pmid = {32239352}, issn = {1435-1463}, mesh = {Anxiety/etiology ; *Cognitive Dysfunction/etiology ; *Gait Disorders, Neurologic ; Humans ; Neuropsychological Tests ; *Parkinson Disease/complications ; }, abstract = {Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD). Until now, anxiety has been consistently related to cognitive deficits and severity of motor symptoms, whereas the association between anxiety and motor subtypes (TD-PD, tremor dominant and PIGD-PD, postural instability/gait disturbances dominant) revealed contrasting results. The present study aims to investigate the relationship between PD motor subtypes and anxiety and to explore whether the relationship between anxiety and cognitive deficits occurs in a specific PD motor subtype. Consecutive PD outpatients were recruited and divided into TD-PD and PIGD-PD groups according to Jankovic et al.'s criteria. All participants underwent a neuropsychological battery to evaluate anxiety, apathy, the global cognitive functioning, memory abilities, executive and visuo-constructional functions. Thirty-six patients with TD-PD and 35 patients with PIGD-PD were enrolled. The two groups did not differ on demographical and clinical variables. As for the severity of anxiety, no significant difference between the two groups was found. Regression analysis revealed that higher anxiety score was associated with poorer performance on constructional visuospatial test in both TD-PD and PIGD-PD. Clinical variables were not associated with anxiety in the two groups. Our findings indicated that the severity of anxiety was not associated with any PD motor subtypes. Moreover, regression analysis revealed that impaired visuo-constructional abilities are related to anxiety independently of PD motor subtypes. Since altered fronto-parietal network might be one of the pathogenetic mechanisms underpinning anxiety and constructional visuospatial deficits, the treatment of cognitive dysfunctions might reduce anxious symptoms.}, } @article {pmid32237875, year = {2020}, author = {Shoshani, A and De-Leon Lendner, K and Nissensohn, A and Lazarovich, G and Aharon-Dvir, O}, title = {Grateful and kind: The prosocial function of gratitude in young children's relationships.}, journal = {Developmental psychology}, volume = {56}, number = {6}, pages = {1135-1148}, doi = {10.1037/dev0000922}, pmid = {32237875}, issn = {1939-0599}, mesh = {Child ; Child Behavior/*physiology ; Child Development/*physiology ; Child, Preschool ; Emotions/*physiology ; Female ; *Helping Behavior ; Humans ; *Interpersonal Relations ; Male ; Theory of Mind/*physiology ; }, abstract = {Three experiments showed that gratitude positively affected preschool children's prosocial behavior. In the studies, the experimenter induced gratitude by giving a token gift and then making a request for help or to share resources. Experiment 1 (N = 126, 4- to 6-year-olds) showed that gratitude increased helping behaviors toward the benefactor, and that emphasis on the benefactor's intention had a significant effect on helping behaviors. Experiment 2 (N = 129, 4- to 6-year-olds) indicated that grateful emotions increased the likelihood that the children would help not only the benefactor but also a stranger. Experiment 3 (N = 133, 3- to 6-year-olds) showed that gratitude motivated preschoolers' sharing behavior with the benefactor. Children's theory-of-mind and their understanding of the benefactor's intention mediated the relationship between children's age, gratitude, and prosociality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).}, } @article {pmid32236595, year = {2020}, author = {Gao, X and Bao, H and Liu, L and Zhu, W and Zhang, L and Yue, L}, title = {Systematic analysis of lysine acetylome and succinylome reveals the correlation between modification of H2A.X complexes and DNA damage response in breast cancer.}, journal = {Oncology reports}, volume = {43}, number = {6}, pages = {1819-1830}, pmid = {32236595}, issn = {1791-2431}, mesh = {Acetylation ; Adult ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Case-Control Studies ; Cell Line, Tumor ; Cell Survival ; *DNA Damage ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*metabolism ; Humans ; Lysine/*chemistry ; MCF-7 Cells ; Middle Aged ; Nuclear Proteins/metabolism ; Nucleophosmin ; Proteomics/*methods ; Succinic Acid/chemistry ; Up-Regulation ; }, abstract = {Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para‑carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.}, } @article {pmid32231493, year = {2020}, author = {Pellini, F and Granuzzo, E and Urbani, S and Mirandola, S and Caldana, M and Lombardi, D and Fiorio, E and Mandarà, M and Pollini, GP}, title = {Male Breast Cancer: Surgical and Genetic Features and a Multidisciplinary Management Strategy.}, journal = {Breast care (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {14-20}, pmid = {32231493}, issn = {1661-3791}, abstract = {BACKGROUND: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role.

METHODS: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants' electronic clinical records were reviewed. Patients' data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives.

RESULTS: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers.

DISCUSSION: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.}, } @article {pmid32227257, year = {2020}, author = {Liu, W and Li, W and Li, Z and Shi, L and Zhao, P and Guo, Z and Tian, J and Wang, Z}, title = {Ultrasound characteristics of sclerosing adenosis mimicking breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {1}, pages = {127-134}, pmid = {32227257}, issn = {1573-7217}, support = {2017RAQXJ178//Harbin Science and Technology Bureau (CN)/ ; }, mesh = {Adenoma/*diagnosis/diagnostic imaging ; Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/*diagnosis/diagnostic imaging ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Sclerosis/*diagnosis/diagnostic imaging ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Sclerosing adenosis (SA) is a benign lesion with complicated pathological components and could mimic breast carcinoma in both clinical palpation and medical imaging findings. The present study was conducted to assess the value of ultrasound (US) characteristics in diagnosing SA and their differentiation from breast carcinoma.

METHODS: We retrospectively reviewed the medical records of 305 women (347 lesions) with invasive ductal carcinoma (IDC) and 54 women with single SA lesion, who had breast excision between April 2016 and July 2018. US BI-RADS atlas and elastography were applied and their associated characteristics were compared between SA and IDC.

RESULTS: The mean age of SA was younger than that of IDC (43.6 ± 7.4 vs 53.2 ± 10.3, P < 0.001). Compared to IDC, SA had more frequency of parallel orientation (94.44% vs 71.76%, P < 0.001) and circumscribed margin (48.15% vs 4.90%, P < 0.001), less frequency of irregular shape (64.81% vs 95.97%, P < 0.001), hypoechoic echotexture (88.89% vs 98.27%, P = 0.002), calcification (12.96% vs 55.04%, P < 0.001), and posterior acoustic changes (3.70% vs 53.89%, P < 0.001) or associated features (architectural distortion, 3.70% vs 59.65%, P < 0.001; duct changes, 18.52% vs 63.40%, P < 0.001). Vascularity absence was more common in SA compared to IDC (35.19% vs 6.63%, P < 0.001). And the elasticity score was lower in SA (2.38 ± 0.60 vs 3.91 ± 0.81, P < 0.001). After adjusting for age, we found spiculated margin, posterior shadowing, calcification, architectural distortion, and vascularity could independently identify the differences between these two entities. After involving elasticity score, the calcification and vascularity could still be independent indicators for differential diagnosis.

CONCLUSION: Understanding SA imaging features will enable radiologists to communicate results to the referring physician consistently, which could benefit a reliable assessment and specific management recommendations. A systematic evaluation of the US BI-RADS atlas together with breast elastography may be a powerful tool to identify SA and differentiate it from breast cancer.}, } @article {pmid32222328, year = {2021}, author = {Lamb, LR and Kim, G and Oseni, TO and Bahl, M}, title = {Noncalcified Ductal Carcinoma In Situ (DCIS): Rate and Predictors of Upgrade to Invasive Carcinoma.}, journal = {Academic radiology}, volume = {28}, number = {3}, pages = {e71-e76}, doi = {10.1016/j.acra.2020.02.011}, pmid = {32222328}, issn = {1878-4046}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Breast Neoplasms/diagnostic imaging/epidemiology ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast/diagnostic imaging/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/epidemiology ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: To determine the upgrade rate of noncalcified ductal carcinoma in situ (DCIS) and features that are associated with risk of upgrade to invasive disease at surgery.

MATERIALS AND METHODS: A retrospective review was conducted of consecutive women who were diagnosed with noncalcified DCIS from January 2007 to December 2016. Patient demographics, imaging findings, biopsy pathology results, and surgical outcomes were reviewed. The unpaired t test, chi-square test, and Fisher's exact test were used to compare features between the cases of DCIS that did and did not upgrade to invasive carcinoma at surgery.

RESULTS: Over a 10-year period, 78 women (mean age 62 years, range 30-88 years) were diagnosed with noncalcified DCIS. Two-thirds (67.9%, 53/78) of cases were detected on screening mammography, and 15.4% (12/78) of diagnoses were made after presentation with an area of palpable concern. The most common mammographic presentations of noncalcified DCIS were mass (51.3%, 40/78) and asymmetry (30.8%, 24/78). Seventeen cases (21.8%, 17/78) were upgraded to invasive ductal carcinoma (IDC) at surgery. Features associated with upgrade risk included older patient age (68.1 versus 60.3 years, OR 1.08, p < 0.01) and family history of breast cancer in a first-degree relative (41.2% [7/17] versus 16.4% [10/61], OR 3.57, p = 0.03).

CONCLUSION: In our study cohort, the upgrade rate of noncalcified DCIS to IDC at surgery is 21.8%. Upgrade risk is associated with older patient age and family history of breast cancer in a first-degree relative.}, } @article {pmid32220886, year = {2020}, author = {Pareja, F and Brown, DN and Lee, JY and Da Cruz Paula, A and Selenica, P and Bi, R and Geyer, FC and Gazzo, A and da Silva, EM and Vahdatinia, M and Stylianou, AA and Ferrando, L and Wen, HY and Hicks, JB and Weigelt, B and Reis-Filho, JS}, title = {Whole-Exome Sequencing Analysis of the Progression from Non-Low-Grade Ductal Carcinoma In Situ to Invasive Ductal Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {14}, pages = {3682-3693}, pmid = {32220886}, issn = {1557-3265}, support = {K12 CA184746/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA Copy Number Variations ; DNA Mutational Analysis ; Disease Progression ; Female ; *Genetic Heterogeneity ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/diagnosis/*genetics/pathology ; Exome Sequencing ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Here, we sought to investigate the level of intralesion genetic heterogeneity in DCIS and the patterns of clonal architecture changes in the progression from DCIS to invasive disease.

EXPERIMENTAL DESIGN: Synchronous DCIS (n = 27) and invasive ductal carcinomas of no special type (IDC-NSTs; n = 26) from 25 patients, and pure DCIS (n = 7) from 7 patients were microdissected separately and subjected to high-depth whole-exome (n = 56) or massively parallel sequencing targeting ≥410 key cancer-related genes (n = 4). Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic analyses were defined using validated computational methods.

RESULTS: DCIS revealed genetic alterations similar to those of synchronously diagnosed IDC-NSTs and of non-related IDC-NSTs from The Cancer Genome Atlas (TCGA), whereas pure DCIS lacked PIK3CA mutations. Clonal decomposition and phylogenetic analyses based on somatic mutations and copy number alterations revealed that the mechanisms of progression of DCIS to invasive carcinoma are diverse, and that clonal selection might have constituted the mechanism of progression from DCIS to invasive disease in 28% (7/25) of patients. DCIS displaying a pattern of clonal selection in the progression to invasive cancer harbored higher levels of intralesion genetic heterogeneity than DCIS where no clonal selection was observed.

CONCLUSIONS: Intralesion genetic heterogeneity is a common feature in DCIS synchronously diagnosed with IDC-NST. DCIS is a nonobligate precursor of IDC-NST, whose mechanisms of progression to invasive breast cancer are diverse and vary from case to case.}, } @article {pmid32220141, year = {2020}, author = {Greenland, NY and Cowan, JE and Zhang, L and Carroll, PR and Chan, E and Stohr, BA and Simko, JP}, title = {Expansile cribriform Gleason pattern 4 has histopathologic and molecular features of aggressiveness and greater risk of biochemical failure compared to glomerulation Gleason pattern 4.}, journal = {The Prostate}, volume = {80}, number = {8}, pages = {653-659}, doi = {10.1002/pros.23977}, pmid = {32220141}, issn = {1097-0045}, mesh = {Aged ; Biopsy/methods ; Cohort Studies ; Disease-Free Survival ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Molecular testing of prostate cancer biopsies with Gleason pattern 4 suggests the expansile cribriform pattern is more aggressive than the glomerulation pattern. These two extreme patterns have not been compared at prostatectomy. We hypothesized that at prostatectomy the expansile cribriform pattern would be associated with histopathologic and molecular features of aggressiveness and with greater risk of biochemical recurrence (BCR) than the glomerulation pattern.

METHODS: In a retrospective cohort study, radical prostatectomy reports with expansile cribriform pattern or glomerulation pattern were analyzed for percentage of total pattern 4, extraprostatic extension (EPE), positive lymph nodes, seminal vesicle invasion (SVI), and intraductal carcinoma (IDC). Cases with pattern 5 or with both expansile cribriform and glomerulations patterns present were excluded. The electronic medical record was reviewed for BCR-free survival and for Decipher test results.

RESULTS: Of 1020 radical prostatectomies from July 2015 to July 2018, 110 (11%) had either expansile cribriform or glomerulation pattern present. The expansile cribriform group was associated with more histopathologic features of aggressiveness, with higher average total percentage pattern 4 (43.7 vs 27.0, P = .002), a trend of greater extensive EPE (32.7% vs 17.2%, P = .06), a trend toward statistical significance of higher rate of SVI (11.5% vs 3.4%, P = .1), greater positive lymph nodes (9.6% vs 0%, P = .02), and a higher percentage of cases with or suspicious for IDC (23.1% vs 8.6%, P = .04). The risk of BCR was 4.4 (1.3-15.4) fold greater for the expansile cribriform group vs the glomerulations group (P = .02). For the 38 patients who underwent Decipher testing, the expansile cribriform group had a high-risk assay category mean score whereas the glomerulations group had an average risk assay category mean score (0.61 vs 0.47, P = .02).

CONCLUSIONS: In a comparison of prostatectomy cases with expansile cribriform pattern to those with glomerulation pattern, the expansile cribriform pattern was associated with more histopathologic features of aggressiveness, greater risk of biochemical failure, and higher scores with a molecular classifier (Decipher) test. These findings underscore the importance of reporting the types of pattern 4 and supports the argument that men with expansile cribriform likely require more aggressive management.}, } @article {pmid32215763, year = {2020}, author = {Frasson, AL and Lichtenfels, M and de Souza, AAB and Vollbrecht, B and Falcone, AB and Frasson, MARM and Barbosa, F}, title = {Risk-reducing mastectomy: a case series of 124 procedures in Brazilian patients.}, journal = {Breast cancer research and treatment}, volume = {181}, number = {1}, pages = {69-75}, pmid = {32215763}, issn = {1573-7217}, mesh = {Adult ; Brazil ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy/methods/statistics & numerical data ; Middle Aged ; Nipples/pathology/surgery ; Organ Sparing Treatments/adverse effects/methods ; Prognosis ; Prophylactic Mastectomy/adverse effects/methods ; Retrospective Studies ; Risk ; }, abstract = {PURPOSE: Women with mutations in breast cancer predisposition genes have a significantly higher lifetime risk of developing breast cancer and can opt for risk-reducing mastectomy. Women with positive family history of cancer can also opt for prophylactic surgery as a preventive method in selected cases. Current studies showed reduced risk of developing breast cancer after prophylactic nipple-sparing mastectomy, however, despite the good clinical outcomes, one of the main concerns regarding nipple-sparing mastectomy (NSM) is the oncological safety of nipple-areola complex preservation. In this study, we aimed to evaluate the indications, complication rates, and unfavorable events of 62 Brazilian patients that underwent risk-reducing NSM from 2004 to 2018.

METHODS: Patient data were reviewed retrospectively and descriptive statistics were utilized to summarize the findings.

RESULTS: The mean patients age was 43.8 years. The main indication for risk-reducing NSM was the presence of pathogenic mutation (53.3%), followed by atypia or lobular carcinoma in situ (25.8), and family history of breast cancer and/or ovarian cancer (20.9%). There were four (3.2%) incidental diagnosis of ductal carcinoma in situ and one invasive ductal carcinoma (0.8%). From the 124 prophylactic NSM performed, two (1.6%) complications had occurred: one (0.8%) infection and one (0.8%) partial nipple necrosis. In a mean follow-up of 50 months, there was one (1.6%) newly diagnosed breast cancer in the 62 patients undergoing prophylactic NSM.

CONCLUSIONS: Our findings demonstrated efficacy and safety to perform NSM as prophylactic surgery with good oncological outcomes and low complication rates in a case series of Brazilian patients.}, } @article {pmid32215758, year = {2020}, author = {Louie, RJ and Gaber, CE and Strassle, PD and Gallagher, KK and Downs-Canner, SM and Ollila, DW}, title = {Trends in Surgical Axillary Management in Early Stage Breast Cancer in Elderly Women: Continued Over-Treatment.}, journal = {Annals of surgical oncology}, volume = {27}, number = {9}, pages = {3426-3433}, pmid = {32215758}, issn = {1534-4681}, support = {K12 CA120780/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; T32 CA233419/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Axilla/pathology/surgery ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Ductal, Breast/pathology/surgery ; Female ; Humans ; Lymph Node Excision/statistics & numerical data/*trends ; Mastectomy ; Medical Overuse/statistics & numerical data/trends ; Neoplasm Staging ; Registries/statistics & numerical data ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; United States/epidemiology ; }, abstract = {INTRODUCTION: In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients.

MATERIALS AND METHODS: We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson-Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67).

CONCLUSIONS: Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.}, } @article {pmid32214847, year = {2020}, author = {Ma, S and Lv, Y and Ma, R}, title = {Prognostic Significance of Metastatic Lymph Nodes Ratio (MLNR) Combined with Protein-Tyrosine Phosphatase H1 (PTPH1) Expression in Operable Breast Invasive Ductal Carcinoma.}, journal = {Cancer management and research}, volume = {12}, number = {}, pages = {1895-1901}, pmid = {32214847}, issn = {1179-1322}, abstract = {PURPOSE: The metastatic lymph node ratio (MLNR) is one of the most important factors in prognostic analysis of breast cancer. The objective of this study was to determine if MLNR combined with protein-tyrosine phosphatase H1 (PTPH1) pathological expression can be used to predict the prognosis of patients with breast invasive ductal carcinoma (IDC) better than one factor only.

PATIENTS AND METHODS: A total of 136 patients with invasive ductal carcinoma (IDC) of breast who underwent modified radical mastectomy and were treated with chemotherapy after operation at Qilu Hospital of Shandong University from December 2008 to October 2011 were included. PTPH1 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PTPH1 expression. A prognostic factor for disease-free survival (DFS) was identified by univariate and multivariate analyses. ROC analysis was used to evaluate the performance of single factors and combined feature.

RESULTS: One hundred and thirty-six patients were included in the analysis. By cut-point survival analysis, MLNR cut-off was designed as 0.2. On multivariate analysis, a MLNR>0.2 was associated with a worse DFS (HR=2.581, 95% CI=1.303-5.113, P=0.007). PTPH1 overexpression is correlated with a better DFS (HR=0.391, 95% CI=0.162-0.945, P=0.037). In addition, MLNR and PTPH1 combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve=0.795 [95% CI=0.694-0.896], P<0.001).

CONCLUSION: These findings indicate that both PTPH1 and MLNR are accurate independent prognostic parameters in patients with IDC of the breast. Better information on IDC prognosis could be obtained from the combined feature.}, } @article {pmid32213441, year = {2020}, author = {Patel, M and Li, C and Aronson, JH and Howie, CM and Maraboyina, S and Prabhu, AV and Kim, T}, title = {The effect of post mastectomy radiation therapy on survival in breast cancer patients with N1mic disease.}, journal = {Breast (Edinburgh, Scotland)}, volume = {51}, number = {}, pages = {50-56}, pmid = {32213441}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/*radiotherapy ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Micrometastasis/*pathology/*radiotherapy ; Propensity Score ; Radiotherapy, Adjuvant ; Retrospective Studies ; SEER Program ; Survival Analysis ; }, abstract = {BACKGROUND: The role of post mastectomy radiation therapy (PMRT) in patients with N1mic breast cancer has not been well defined. A retrospective analysis was performed using the SEER database to evaluate the impact of PMRT on survival in patients with N1mic breast cancer.

MATERIALS AND METHODS: Women with T1-T2, N1mic, M0 breast cancer who had undergone mastectomy were analyzed. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log rank test while multivariate analysis was performed with Cox proportional hazards regression. Sub-cohort analysis with propensity score matching was used to assess differences in survival among patients undergoing PMRT vs no PMRT. Comparisons were considered statistically significant at P < 0.05.

RESULTS: Among 5878 patients, 1202 (20%) underwent PMRT. On univariate analysis, PMRT was a significant predictor of CSS, but not OS. There was no difference in either OS or CSS between the PMRT vs no PMRT groups on multivariate Cox regression analysis and after propensity score matching.

CONCLUSIONS: Among patients with T1-T2, N1mic, M0 breast IDC from the SEER database, there was no difference in either OS or CSS among patients who underwent PMRT vs no PMRT. These results suggest that PMRT does not impact survival among breast cancer patients with N1mic disease. However, additional prospective studies with longer follow up are necessary for further evaluation.}, } @article {pmid32212794, year = {2020}, author = {Rasmy, A and Sorour, Y}, title = {Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {21}, number = {3}, pages = {683-691}, pmid = {32212794}, issn = {2476-762X}, mesh = {Adult ; Aged ; Body Mass Index ; Breast Neoplasms/complications/*therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Obesity/*complications ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.

PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI ≥ 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.

RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).

CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.}, } @article {pmid32211515, year = {2020}, author = {Chelban, V and Carecchio, M and Rea, G and Bowirrat, A and Kirmani, S and Magistrelli, L and Efthymiou, S and Schottlaender, L and Vandrovcova, J and Salpietro, V and Salsano, E and Pareyson, D and Chiapparini, L and Jan, F and Ibrahim, S and Khan, F and Qarnain, Z and Groppa, S and Bajaj, N and Balint, B and Bhatia, KP and Lees, A and Morrison, PJ and Wood, NW and Garavaglia, B and Houlden, H}, title = {MYORG-related disease is associated with central pontine calcifications and atypical parkinsonism.}, journal = {Neurology. Genetics}, volume = {6}, number = {2}, pages = {e399}, pmid = {32211515}, issn = {2376-7839}, abstract = {OBJECTIVE: To identify the phenotypic, neuroimaging, and genotype-phenotype expression of MYORG mutations.

METHODS: Using next-generation sequencing, we screened 86 patients with primary familial brain calcification (PFBC) from 60 families with autosomal recessive or absent family history that were negative for mutations in SLC20A2, PDGFRB, PDGBB, and XPR1. In-depth phenotyping and neuroimaging investigations were performed in all cases reported here.

RESULTS: We identified 12 distinct deleterious MYORG variants in 7 of the 60 families with PFBC. Overall, biallelic MYORG mutations accounted for 11.6% of PFBC families in our cohort. A heterogeneous phenotypic expression was identified within and between families with a median age at onset of 56.4 years, a variable combination of parkinsonism, cerebellar signs, and cognitive decline. Psychiatric disturbances were not a prominent feature. Cognitive assessment showed impaired cognitive function in 62.5% of cases. Parkinsonism associated with vertical nuclear gaze palsy was the initial clinical presentation in 1/3 of cases and was associated with central pontine calcifications. Cerebral cortical atrophy was present in 37% of cases.

CONCLUSIONS: This large, multicentric study shows that biallelic MYORG mutations represent a significant proportion of autosomal recessive PFBC. We recommend screening MYORG mutations in all patients with primary brain calcifications and autosomal recessive or negative family history, especially when presenting clinically as atypical parkinsonism and with pontine calcification on brain CT.}, } @article {pmid32210624, year = {2020}, author = {Cai, SM and Wang, HY and Zhang, XY and Zhang, L and Zhu, QL and Li, JC and Sun, Q and Jiang, YX}, title = {The Vascular Index of Superb Microvascular Imaging Can Improve the Diagnostic Accuracy for Breast Imaging Reporting and Data System Category 4 Breast Lesions.}, journal = {Cancer management and research}, volume = {12}, number = {}, pages = {1819-1826}, pmid = {32210624}, issn = {1179-1322}, abstract = {PURPOSE: To investigate whether the vascular index (VI) of superb microvascular imaging (SMI) could improve the diagnostic efficiency for BI-RADS 4 breast lesions and reduce the number of unnecessary biopsies.

PATIENTS AND METHODS: For this study, we selected 222 consecutive BI-RADS 4 breast lesions detected by ultrasound and confirmed by pathology from January 2016 to October 2018. A VI of 4.0 was set as the cutoff value to degrade BI-RADS classification. We calculated the accuracy, sensitivity and PPV of a BI-RADS diagnosis alone and the combination of BI-RADS and the VI.

RESULTS: Pathologically, of the 222 lesions, 129 were confirmed to be benign, and 93 were found to be malignant. A VI of 4.0 was set as the cutoff value; when the VI≤4.0, those BI-RADS 4 masses were downgraded one level (4C-4B, 4B-4A, 4A-3) to an integral BI-RADS grade, while the others maintained the conventional grade. A total of 54 BI-RADS 4 lesions were degraded to BI-RADS 3, including 53 benign lesions and 1 malignant lesion. The diagnostic accuracy (65.3% vs 41.9%) and PPV (54.8% vs 41.9%) were significantly improved. The sensitivity decreased slightly (98.9% vs 100%) because 1 of the 54 downgraded BI-RADS 4 lesions, which had a pathological type of invasive ductal carcinoma, was incorrectly downgraded.

CONCLUSION: SMI is a noninvasive tool for visualizing the vascular structure with high-resolution microvascular images. As a quantitative index, the VI can be used to appropriately downgrade benign lesions classified as BI-RADS 4, which can improve the diagnostic accuracy and PPV and reduce unnecessary biopsies.}, } @article {pmid32210610, year = {2020}, author = {Yap, RV and De La Serna, FM}, title = {Outcomes of Sentinel Lymph Node Biopsy Using Blue Dye Method for Early Breast Cancer - A Single-Institution Experience in the Philippines.}, journal = {Breast cancer (Dove Medical Press)}, volume = {12}, number = {}, pages = {37-44}, pmid = {32210610}, issn = {1179-1314}, abstract = {PURPOSE: This study aimed to share our experience with SLNB in the Filipino population with early breast cancer.

PATIENTS AND METHODS: A retrospective review was done on all patients with confirmed invasive breast carcinoma, tumor size of 5 cm or less (T1/T2), who preoperatively had no clinical signs of axillary metastasis and subsequently underwent SLNB with blue dye method from January 01, 2008 to December 31, 2017. Clinicopathologic profiles were recorded. Outcomes of patients who had SLNB only were assessed.

RESULTS: One hundred twenty-nine patients matched the inclusion criteria with a mean age of 54.3 years. The majority (88.4%) had a total mastectomy. Invasive ductal carcinoma (65.1%) was the most common tumor. Estrogen and progesterone receptors were positive in 69% and 61.2% respectively while only 28.7% were HER2 positive. SLNB was successfully carried out in 126 (97.7%) patients with a range of 2-4 SLNs harvested. Thirty-four (26.4%) patients had completion ALND. With a median of 25 months follow-up, 75 out of 95 patients who underwent SLNB alone had follow-up data. Forty-six (61.3%) patients had seroma formation. One (1.3%) patient developed arm paresthesia, 2 (2.7%) local (chest wall) and 2 (2.7%) axillary recurrences after a negative SLNB. None of the patients developed lymphedema.

CONCLUSION: The blue dye method alone is acceptable and can be readily employed in institutions with limited resources. Even with the limited population, the morbidity and oncologic outcomes of patients who underwent SLNB alone were low and comparable to similar international published data. SLNB should be the preferred method for staging the axilla.}, } @article {pmid32209879, year = {2020}, author = {Liu, Q and Zhang, J and Kulkarni, HR and Baum, RP}, title = {177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {5}, pages = {e232-e235}, doi = {10.1097/RLU.0000000000003005}, pmid = {32209879}, issn = {1536-0229}, mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy ; Octreotide/*analogs & derivatives/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/*metabolism ; Treatment Outcome ; }, abstract = {Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.}, } @article {pmid32206399, year = {2020}, author = {Liu, W and Zhang, R and Ling, Y and Tang, H and She, R and Wei, G and Gong, X and Lu, Y}, title = {Automatic recognition of breast invasive ductal carcinoma based on terahertz spectroscopy with wavelet packet transform and machine learning.}, journal = {Biomedical optics express}, volume = {11}, number = {2}, pages = {971-981}, pmid = {32206399}, issn = {2156-7085}, abstract = {We demonstrate an automatic recognition strategy for terahertz (THz) pulsed signals of breast invasive ductal carcinoma (IDC) based on a wavelet entropy feature extraction and a machine learning classifier. The wavelet packet transform was implemented into the complexity analysis of the transmission THz signal from a breast tissue sample. A novel index of energy to Shannon entropy ratio (ESER) was proposed to distinguish different tissues. Furthermore, the principal component analysis (PCA) method and machine learning classifier were further adopted and optimized for automatic classification of the THz signal from breast IDC sample. The areas under the receiver operating characteristic curves are all larger than 0.89 for the three adopted classifiers. The best breast IDC recognition performance is with the precision, sensitivity and specificity of 92.85%, 89.66% and 96.67%, respectively. The results demonstrate the effectiveness of the ESER index together with the machine learning classifier for automatically identifying different breast tissues.}, } @article {pmid32206145, year = {2020}, author = {Boltežar, L and Gašljević, G and Novaković, S and Stegel, V and Škof, E}, title = {An interesting case of likely BRCA2 related bilateral breast cancer with metastasis in the fimbrial part of fallopian tube.}, journal = {Hereditary cancer in clinical practice}, volume = {18}, number = {}, pages = {7}, pmid = {32206145}, issn = {1731-2302}, abstract = {BACKGROUND: In a patient with a germline BRCA2 pathogenic variant with breast cancer, an adnexal mass can represent either a metachronous primary tumor or a metastasis of the breast cancer. A clear distinction between those two possibilities is crucial since treatments differ substantially and so does survival of the patient.

CASE PRESENTATION: We present a case of a 47-year-old patient with bilateral breast carcinoma with a germline BRCA2 pathogenic variant. The first manifestation of the disease was a lump in her left breast in 1998, histological report was invasive ductal carcinoma, triple-negative. She was treated with surgery, chemotherapy and radiotherapy. In 2011 a new occult carcinoma was found in her right axilla, however the specimen was estrogen receptor (ER) and progesterone receptor (PgR) positive. She was treated as a new primary occult carcinoma of the right breast with surgery, radiotherapy and adjuvant hormonal treatment. In 2016 a mass in the left adnexa was found with imaging techniques. She underwent surgery as if it was primary ovarian cancer, yet histology revealed it was a metastasis of a triple-negative breast carcinoma in the fimbrial part of the left Fallopian tube. She received adjuvant chemotherapy after surgery and is now in complete remission.

CONCLUSION: We present an interesting and quite rare case of two primary breast carcinomas in a patient with a known BRCA2 pathogenic variant with metastasis in the fimbrial part of the left Fallopian tube. We conclude that there were two primary breast tumours and the one from 2011 spread into the fimbrial part of the left Fallopian tube in 2016. Despite the fact that molecular analyses could not confirm the joint tumour origin, we believe that there was a receptor status conversion over time explaining different receptor status. The possibility of a triple-negative metastasis from the tumour treated in 1998 is less probable. With both of aforementioned possibilities being prognostically unfavourable, the patients' outcome is so far excellent and she was in complete remission at the time of writing this article.}, } @article {pmid32205960, year = {2020}, author = {Shah, T and Shah, N and Vijay, DG and Patel, B and Patel, S}, title = {Male Breast Cancer: Current Trends-a Tertiary Care Centre Experience.}, journal = {Indian journal of surgical oncology}, volume = {11}, number = {1}, pages = {7-11}, pmid = {32205960}, issn = {0975-7651}, abstract = {Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men. Occurrence of male breast cancer peaks at age 71 years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Presentation is usually a lump or nipple inversion, but is often late, with more than 40% of individuals having stage III or IV disease. We retrospectively reviewed 25 male patients with breast cancer who came to the HCG Cancer Centre, Ahmedabad between 2014 and 2018, and their demographic details, tumor profile, and radiological, histopathological as well as luminal profile findings were studied. The average age at presentation and detection of male breast cancer was 61.08 years. Incidence of male ca. breast over these 4 years was 4.75/year which had a significant increase compared with our own data in the last 8 years (3/year). Male to female ratio for ca. breast was 1:61. One out of 25 (4%) patients had gynaecomastia. The most common histology was invasive ductal carcinoma-not otherwise specified with none of the patients having lobular carcinoma. Majority of patients were ER/PR positive and HER-2 negative. Male breast cancer is having a rising incidence, which in our study is 1.56%. Males have relatively older age at presentation and stage-by-stage treatment remains the same. Males are more likely to be having prognostically favourable luminal subtypes. Male breast cancer in Indian population is currently experiencing an increasing trend. Improved awareness amongst patients and high index of suspicion by the clinicians along with accurate diagnostic techniques help detect the disease at an earlier stage culminating into prolonged overall and disease-free survival.}, } @article {pmid32204493, year = {2020}, author = {Bao, J and Markovic, T and Brancato, L and Kil, D and Ocket, I and Puers, R and Nauwelaers, B}, title = {Novel Fabrication Process for Integration of Microwave Sensors in Microfluidic Channels.}, journal = {Micromachines}, volume = {11}, number = {3}, pages = {}, pmid = {32204493}, issn = {2072-666X}, support = {G0A1220N//Fonds Wetenschappelijk Onderzoek/ ; 340931/ERC_/European Research Council/International ; AKUL 034//KU Leuven/ ; microwave microbiology//KU Leuven/ ; ZW1115//KU Leuven/ ; }, abstract = {This paper presents a novel fabrication process that allows integration of polydimethylsiloxane (PDMS)-based microfluidic channels and metal electrodes on a wafer with a micrometer-range alignment accuracy. This high level of alignment accuracy enables integration of microwave and microfluidic technologies, and furthermore accurate microwave dielectric characterization of biological liquids and chemical compounds on a nanoliter scale. The microfluidic interface between the pump feed lines and the fluidic channels was obtained using magnets fluidic connection. The tube-channel interference and the fluidic channel-wafer adhesion was evaluated, and up to a pressure of 700 mBar no leakage was observed. The developed manufacturing process was tested on a design of a microwave-microfluidic capacitive sensor. An interdigital capacitor (IDC) and a microfluidic channel were manufactured with an alignment accuracy of 2.5 μm. The manufactured IDC sensor was used to demonstrate microwave dielectric sensing on deionized water and saline solutions with concentrations of 0.1, 0.5, 1, and 2.5 M.}, } @article {pmid32202536, year = {2020}, author = {Szentirmai, E and Giannico, GA}, title = {Intraductal carcinoma of the prostate.}, journal = {Pathologica}, volume = {112}, number = {1}, pages = {17-24}, pmid = {32202536}, issn = {1591-951X}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Prostatectomy/trends ; Prostatic Neoplasms/*diagnosis/*genetics/therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.}, } @article {pmid32201658, year = {2020}, author = {Manthri, S and Sharma, P and Mejbel, HA and Singal, S and Jaishankar, D}, title = {Third Line Eribulin for Triple-negative Metastatic Breast Ductal Carcinoma Resulting in Extended Progression-free Survival of 57 Months.}, journal = {Cureus}, volume = {12}, number = {2}, pages = {e6980}, pmid = {32201658}, issn = {2168-8184}, abstract = {Eribulin is a non-taxane microtubule inhibitor approved for the treatment of metastatic breast carcinoma after two prior chemotherapeutic regimens. We report a patient with extended progression-free survival (PFS) of more than 57 months with metastatic breast carcinoma treated with eribulin in the third-line setting. A 48-year-old lady was diagnosed with stage IIA (pT2N0M0), high grade, triple-negative, invasive ductal carcinoma (IDC) of the left breast on core needle biopsy. She underwent neoadjuvant chemotherapy with adriamycin, and cyclophosphamide followed by a negative sentinel lymph node (SLN) biopsy. Subsequent mastectomy and axillary lymph node dissection revealed a 2.5 cm, high grade, triple-negative IDC with three additional lymph nodes negative for metastatic carcinoma, consistent with the initial diagnosis. Eight months into the surveillance program, the patient developed a 2.8 cm right lower lobe (RLL) lung mass with standard uptake value (SUV) of 27 on positron emission tomography-computed tomography (PET/CT). Core needle biopsy of the lung lesion revealed sheets of poorly differentiated carcinoma, immunophenotypically compatible with the initial diagnosis of breast pathology. She then commenced single-agent paclitaxel in the 1st line metastatic setting with a significant decrease in RLL lung mass to less than 1 cm with an SUV of 1.7 noted. The patient developed progression after seven months and started 2nd line gemcitabine noting initial improvement and subsequent stable disease for a period of 12 months. Eventual progression of RLL lung nodule measuring 2.1 cm with SUV of 10 noted. Initiated 3rd line eribulin with a notable response on imaging studies within three months and with no evidence of disease (NED) on scans over the subsequent 57 months. Eribulin related mild neuropathy superimposed on previous paclitaxel associated grade 2 neuropathy required a 20% eribulin dose reduction. The patient is currently clinically and radiographically stable with plateaued serum tumor markers. Our patient has shown excellent response and tolerance to eribulin with PFS of over 57 months (nineteen times the norm) which is rare.}, } @article {pmid32197364, year = {2020}, author = {Bao, J and Maenhout, G and Markovic, T and Ocket, I and Nauwelaers, B}, title = {A Microwave Platform for Reliable and Instant Interconnecting Combined with Microwave-Microfluidic Interdigital Capacitor Chips for Sensing Applications.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {6}, pages = {}, pmid = {32197364}, issn = {1424-8220}, support = {microwave microbiology//KU Leuven/ ; G0A1220N//Fonds Wetenschappelijk Onderzoek/ ; IS23918N//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {This work presents a novel platform conceived as an interconnect box (ICB) that brings high-frequency signals from microwave instruments to consumable lab-on-a-chip devices. The ICB can be connected to instruments with a standard coaxial connector and to consumable chips by introducing a spring-levered interface with elastomer conductive pins. With the spring-system, microwave-microfluidic chips can be mounted reliably on the setup in a couple of seconds. The high-frequency interface within the ICB is protected from the environment by an enclosure having a single slit for mounting the chip. The stability and repeatability of the contact between the ICB and inserted consumable chips are investigated to prove the reliability of the proposed ICB. Given the rapid interconnecting of chips using the proposed ICB, five different interdigital capacitor (IDC) designs having the same sensing area were investigated for dielectric permittivity extraction of liquids. The designed IDCs, embedded in a polydimethylsiloxane (PDMS) channel, were fabricated with a lift-off gold patterning technology on a quartz substrate. Water-Isopropanol (IPA) mixtures with different volume fractions were flushed through the channel over IDCs and sensed based on the measured reflection coefficients. Dielectric permittivity was extracted using permittivity extraction techniques, and fitted permittivity data shows good agreement with literature from 100 to 25 GHz.}, } @article {pmid32195332, year = {2020}, author = {Kader, T and Elder, K and Zethoven, M and Semple, T and Hill, P and Goode, DL and Thio, N and Cheasley, D and Rowley, SM and Byrne, DJ and Pang, JM and Miligy, IM and Green, AR and Rakha, EA and Fox, SB and Mann, GB and Campbell, IG and Gorringe, KL}, title = {The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma.}, journal = {NPJ breast cancer}, volume = {6}, number = {}, pages = {9}, pmid = {32195332}, issn = {2374-4677}, abstract = {Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma.}, } @article {pmid32193143, year = {2020}, author = {Shiino, S and Yoshida, M and Tokura, M and Watase, C and Murata, T and Jimbo, K and Takayama, S and Suto, A and Satomi, K and Miyagi Maeshima, A and Kikuchi, M and Uchiyama, N and Kinoshita, T}, title = {Locally advanced triple negative breast cancer arising from fibroadenoma with complete response to neoadjuvant chemotherapy: A case report.}, journal = {International journal of surgery case reports}, volume = {68}, number = {}, pages = {234-238}, pmid = {32193143}, issn = {2210-2612}, abstract = {INTRODUCTION: Breast cancer arising from benign fibroadenoma (FA) is rare. The histological type of the former was either carcinoma in situ or early-stage invasive breast carcinoma with hormone receptor positive/HER2 (human epidermal growth factor receptor-2)-negative phenotype. Meanwhile, advanced breast cancer of triple negative (TN) phenotype such as our case is extremely uncommon and clinically challenging.

PRESENTATION OF CASE: We experienced a case of a 53-year-old woman that had invasive ductal carcinoma of TN phenotype in FA with multiple lymph node metastases. After receiving neoadjuvant chemotherapy (NAC), she underwent breast mastectomy and axillary dissection. The pathological examination on postoperative specimens revealed the dense fibrous stroma in the FA without any residual viable tumor cells and was considered as pathological complete response (pCR).

DISCUSSION: This is the first report presenting a case of NAC treatment for invasive ductal carcinoma (IDC) in FA. Furthermore, the patient achieved pCR even if IDC was located within FA. Diagnosing breast cancer in FA may be challenging as the carcinoma component may be hidden by the FA component. If imaging of FA became larger or abnormal changes during follow-up examinations, needle biopsy should be recommended for assessment of the lesion positively.

CONCLUSION: This is the first report presenting a case of advanced breast cancer in FA of TN phenotype with multiple lymph node metastases who achieved pCR even if IDC was located within FA.}, } @article {pmid32190711, year = {2020}, author = {Lee, RA and Vo, DT and Zurko, JC and Griffin, RL and Rodriguez, JM and Camins, BC}, title = {Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa064}, pmid = {32190711}, issn = {2328-8957}, abstract = {BACKGROUND: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.

METHODS: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.

RESULTS: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).

CONCLUSIONS: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.}, } @article {pmid32190504, year = {2020}, author = {Ibrahim, ME and Saleh, M and Ali, A and Alavi, N}, title = {Multiple Primary Malignant Neoplasms: An Unusual Case of Metachronous Breast Ductal and Squamous Cell Carcinomas.}, journal = {Cureus}, volume = {12}, number = {2}, pages = {e6954}, pmid = {32190504}, issn = {2168-8184}, abstract = {Multiple primary malignant neoplasms (MPMN) are generally defined as the co-occurrence of multiple primary malignant neoplasms of distinct histology in the same individual. Second and higher-order primary malignancies now comprise about 18% of all incidence of cancer in the USA. The incidence ratio of developing multiple primary cancers (MPCs) in female cancer survivors is 1.17 to 1.6. In women with breast cancer, the incidence ratio is even higher, according to age at diagnosis of breast cancer. However, the concurrence of breast cancer and squamous cell carcinoma is not described in the literature. Primary squamous cell carcinoma of bone is also rare in the skeletal system other than in the skull, with only three such cases reported in the English literature. We present a case of a 59-year-old woman with high-grade primary invasive ductal carcinoma of the breast and second distinct squamous cell carcinoma metastasis to the bone of unknown primary site. A search for a primary squamous cell carcinoma, including CT head and neck, CT chest, colposcopy, esophagogastroduodenoscopy (EGD) and colonoscopy, did not show any evidence of a primary site.}, } @article {pmid32190027, year = {2020}, author = {Young, CR and Harigopal, M and Pucar, D}, title = {Rapid progression of carcinoma en cuirasse breast dermal metastases on [18]F-fludeoxyglucose positron emission tomography-computed tomography.}, journal = {World journal of nuclear medicine}, volume = {19}, number = {1}, pages = {65-68}, pmid = {32190027}, issn = {1450-1147}, abstract = {Cancer in the dermis of the breast has a poor prognosis. The breast dermis can become malignantly involved primarily in inflammatory breast cancer, through the direct extension of locally advanced breast cancer, or metastatically from an underlying breast mass or a distant primary malignancy (e.g., gastric adenocarcinoma). Breast dermal metastases have the shortest median survival among them. Breast dermal metastases are classified into eight clinicohistopathologic groups, one of which is carcinoma en cuirasse. We present a case of a 52-year-old female with a history of invasive ductal carcinoma, Stage IIIC (pT2N3a), treated with lumpectomy, axillary node dissection, and chemoradiation therapy that recurred as carcinoma en cuirasse breast dermal metastases. Through [18]F-fludeoxyglucose positron emission tomography-computed tomography ([18]F-FDG PET-CT) and clinical images, the case illustrates the rapid progression and devastating consequences of carcinoma en cuirasse breast dermal metastases over a 4-month period despite optimal therapy. Furthermore, the case emphasizes the sensitivity of [18]F-FDG PET-CT to detect pathology in the breast dermis. Finally, the case highlights the crucial role that nuclear medicine physicians play in helping clinical colleagues differentiate between the various breast dermal malignant manifestations and benign mastitis, a common confounder in postradiation patients.}, } @article {pmid32187826, year = {2020}, author = {Hasan, SS and Jabs, M and Taylor, J and Wiedmann, L and Leibing, T and Nordström, V and Federico, G and Roma, LP and Carlein, C and Wolff, G and Ekim-Üstünel, B and Brune, M and Moll, I and Tetzlaff, F and Gröne, HJ and Fleming, T and Géraud, C and Herzig, S and Nawroth, PP and Fischer, A}, title = {Endothelial Notch signaling controls insulin transport in muscle.}, journal = {EMBO molecular medicine}, volume = {12}, number = {4}, pages = {e09271}, pmid = {32187826}, issn = {1757-4684}, support = {FI 1569/3-1//Deutsche Forschungsgemeinschaft (DFG)/International ; SFB1366 (project C4 and B3)//Deutsche Forschungsgemeinschaft (DFG)/International ; 394046768//Deutsche Forschungsgemeinschaft (DFG)/International ; SFB1118//Deutsche Forschungsgemeinschaft (DFG)/International ; SFB1123//Deutsche Forschungsgemeinschaft (DFG)/International ; SFB894//Deutsche Forschungsgemeinschaft (DFG)/International ; //Chica and Heinz Schaller Foundation/International ; }, mesh = {Animals ; Endothelial Cells/*metabolism ; Glucose/metabolism ; *Insulin/metabolism ; *Insulin Resistance ; Mice ; Muscle, Skeletal/*metabolism ; Receptors, Notch/*metabolism ; *Signal Transduction ; }, abstract = {The role of the endothelium is not just limited to acting as an inert barrier for facilitating blood transport. Endothelial cells (ECs), through expression of a repertoire of angiocrine molecules, regulate metabolic demands in an organ-specific manner. Insulin flux across the endothelium to muscle cells is a rate-limiting process influencing insulin-mediated lowering of blood glucose. Here, we demonstrate that Notch signaling in ECs regulates insulin transport to muscle. Notch signaling activity was higher in ECs isolated from obese mice compared to non-obese. Sustained Notch signaling in ECs lowered insulin sensitivity and increased blood glucose levels. On the contrary, EC-specific inhibition of Notch signaling increased insulin sensitivity and improved glucose tolerance and glucose uptake in muscle in a high-fat diet-induced insulin resistance model. This was associated with increased transcription of Cav1, Cav2, and Cavin1, higher number of caveolae in ECs, and insulin uptake rates, as well as increased microvessel density. These data imply that Notch signaling in the endothelium actively controls insulin sensitivity and glucose homeostasis and may therefore represent a therapeutic target for diabetes.}, } @article {pmid32183280, year = {2020}, author = {Böhm, ME and Razavi, M and Flach, CF and Larsson, DGJ}, title = {A Novel, Integron-Regulated, Class C β-Lactamase.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {32183280}, issn = {2079-6382}, support = {2018-02835//Vetenskapsrådet/ ; 2018-05771//Vetenskapsrådet/ ; 2018-00787//Svenska Forskningsrådet Formas/ ; }, abstract = {AmpC-type β-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all β-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is induced in response to exposure to β-lactams. Regulation of mobile ampC expression is in many cases less controlled, giving rise to constitutively resistant strains with increased potential for development or acquisition of additional resistances. We present here the identification of two integron-encoded ampC genes, blaIDC-1 and blaIDC-2 (integron-derived cephalosporinase), with less than 85% amino acid sequence identity to any previously annotated AmpC. While their resistance pattern identifies them as class C β-lactamases, their low isoelectric point (pI) values make differentiation from other β-lactamases by isoelectric focusing impossible. To the best of our knowledge, this is the first evidence of an ampC gene cassette within a class 1 integron, providing a mobile context with profound potential for transfer and spread into clinics. It also allows bacteria to adapt expression levels, and thus reduce fitness costs, e.g., by cassette-reshuffling. Analyses of public metagenomes, including sewage metagenomes, show that the discovered ampCs are primarily found in Asian countries.}, } @article {pmid32181047, year = {2020}, author = {Bianchi, A and Pozza, S and Giovannacci, L and van den Berg, JC}, title = {Phlegmasia Cerulea Dolens in a Patient with Breast Cancer and Inferior Vena Cava Hypoplasia.}, journal = {Case reports in vascular medicine}, volume = {2020}, number = {}, pages = {2176848}, pmid = {32181047}, issn = {2090-6986}, abstract = {BACKGROUND: No clear guidelines exist for the management of phlegmasia cerulea dolens. This case report shows how a hybrid approach might be successful. It also shows how rare pathologies can combine to create a life- and limb-threatening condition. Case Presentation. A 75-year-old man, known for nephrotic syndrome currently under investigation, presented to the emergency department with a 24-hour history of left leg swelling followed by intense pain. The left lower limb showed a phlegmasia cerulean dolens. Renal function, coagulation profile, and inflammatory parameters were normal; D-Dimers 5,6 mg/L. The CT scan showed juxtarenal thrombosis of the hypoplastic IVC, involving both renal veins, reaching the left iliac-femoral-popliteal axis, with collateralization to the pelvic and mesenteric veins, associated with bilateral segmental pulmonary embolisms. A suspected left breast nodule was also found. Intravenous heparin was immediately administered, and urgent hybrid procedure with surgical thrombectomy and venous angiography and thromboaspiration, liberating the iliolumbar collaterals, was performed. A lateral leg fasciotomy was mandatory due to the phlegmasia cerulea. Postoperative Doppler US showed a good venous compressibility of the left leg. Thrombophilia screening was negative. The breast nodule was biopsied showing an invasive ductal carcinoma. The patient was discharged with oral rivaroxaban and indication for left mastectomy and oncological therapy with aromatase inhibitors.

CONCLUSION: This case highlights the dramatic consequence of different risk factors for venous thromboembolism as cancer and nephrotic syndrome in a patient with hypoplasia of the inferior cava vein. Venous thromboaspiration has been used in order to timely recanalize important collaterals. Phlegmasia cerulea dolens was resolved after the procedure and lateral calf fasciotomy. Further evidence is needed to clearly define the role of venous thromboaspiration in the treatment of complex proximal deep venous thrombosis of the lower extremity.}, } @article {pmid32178425, year = {2020}, author = {Fernández-Nogueira, P and Mancino, M and Fuster, G and Bragado, P and Puig, MP and Gascón, P and Casado, FJ and Carbó, N}, title = {Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy.}, journal = {Journal of clinical medicine}, volume = {9}, number = {3}, pages = {}, pmid = {32178425}, issn = {2077-0383}, support = {2018, BBM-TRA-0041//Fundación BBVA/ ; 2017_SGR_1305//by Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement/ ; -//Cellex Foundation/ ; }, abstract = {Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.}, } @article {pmid32173132, year = {2021}, author = {Palacios-Fuenmayor, LJ and Naranjo-Isaza, AM and Serna-Ortiz, CA and Mosquera-Castro, DA and Arbeláez-Leon, LM and Gómez-Wolff, LR and García-García, HI and Sánchez-Patiño, LA}, title = {Evaluation of the pathologic response to neoadjuvant treatment in rectal cancer. Experience at the Instituto de Cancerología de Medellín (Colombia, 2011-2017).}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {86}, number = {1}, pages = {13-20}, doi = {10.1016/j.rgmx.2019.11.006}, pmid = {32173132}, issn = {2255-534X}, abstract = {INTRODUCTION AND AIMS: Neoadjuvant therapy in rectal cancer is associated with a decrease in tumor size and is the therapeutic indication for patients with T3 or T4 tumors or lymph node involvement. Our aim was to describe the frequency of pathologic response and the survival rate in patients that underwent neoadjuvant therapy for rectal cancer.

MATERIALS AND METHODS: A retrospective follow-up study with a survival analysis was conducted. Patients with locally advanced rectal cancer that received neoadjuvant treatment and were operated on at the Instituto de Cancerología Las Américas (Medellín, Colombia) were analyzed. Survival was calculated using the Kaplan-Meier method.

RESULTS: A total of 152 patients were included. Mean patient age was 59 years (12.8 SD), 53.9% were men, and 58.6% of the patients were diagnosed with stage IIIB disease. The pathologic complete response (pCR) was achieved in 17% of the patients. A total of 146 (96.1%) patients received the chemoradiotherapy protocol. Fifty-two (34.2%) patients developed metastasis and/or relapse, and one (3.8%) of those patients had presented with pCR. The median follow-up period was 33 months (Q1-Q3: 20-45), with an overall survival rate of 79.5% (95% CI 70.9-85.8). The 5-year survival rate for the patients that had pCR was 80% (95% CI 20.3-96.9).

CONCLUSIONS: The frequency of pCR was similar to that in other published studies and disease recurrence was lower, compared with patients with no response. The 5-year survival rate in patients with pCR was high, albeit lower than that reported in other studies.}, } @article {pmid32172190, year = {2020}, author = {Ye, F and Yu, P and Li, N and Yang, A and Xie, X and Tang, H and Liu, P}, title = {Prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in breast: A meta-analysis of PSM studies.}, journal = {Breast (Edinburgh, Scotland)}, volume = {51}, number = {}, pages = {11-20}, pmid = {32172190}, issn = {1532-3080}, mesh = {Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/*mortality/*pathology ; Carcinoma, Papillary/*mortality/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; Propensity Score ; Survival Analysis ; Survival Rate ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare histological subtype of breast cancer. The outcome of IMPC remains controversial; we conducted a meta-analysis of propensity score matching (PSM) studies to evaluate the prognostic difference between IMPC and invasive ductal carcinoma (IDC).

METHODS: We searched PubMed, EMBASE and the Cochrane library for PSM studies comparing survival data between IMPC and IDC. The summarized odds ratios (ORs) and 95% confidence interval (95% CI) are calculated by STATA software utilizing fixed-effect or random-effect models, depending on the heterogeneity of the eligible studies.

RESULTS: Eight PSM studies including 2102 IMPC patients are included in the meta-analysis. Compared with IDC, IMPC has a similar overall survival (OS) (estimated OR = 0.87, 95% CI: 0.61-1.25), but a shorter relapse free survival (RFS) (estimated OR = 1.31, 95% CI: 1.06-1.61); the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC (estimated OR = 3.60, 95% CI: 1.99-6.52). Funnel plots and Egger's tests are used to evaluate publication bias and the p value for OS and RFS are 0.036 and 0.564 respectively.

CONCLUSIONS: Our results demonstrate that compared with IDC, IMPC exhibits a similar, even favorite OS, but a shorter RFS; and the shorter RFS might owe to the significantly higher loco-regional recurrence rate of IMPC. These results could contribute to the individualized therapy and follow-up strategies for IMPC patients.}, } @article {pmid32167041, year = {2020}, author = {Dixon, J and Jasra, B and Ankola, A and Sharma, S and Letter, H}, title = {Bracketed Radioactive Seed Localization for Breast Conservation Surgery.}, journal = {The American surgeon}, volume = {86}, number = {2}, pages = {90-94}, pmid = {32167041}, issn = {1555-9823}, mesh = {Breast Neoplasms/diagnostic imaging/*surgery ; Calcinosis/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging/*surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*surgery ; Female ; Fiducial Markers ; Humans ; Image-Guided Biopsy ; Iodine Radioisotopes/*administration & dosage ; Mammography ; Margins of Excision ; Mastectomy, Segmental/*methods ; Organ Sparing Treatments/*methods ; Reoperation/statistics & numerical data ; Retrospective Studies ; }, abstract = {We aimed to evaluate the surgical margin outcomes and re-excision rates in patients undergoing bracketed seed localization of biopsy-proven breast cancer detected on screening mammogram. After approval by our Institutional Review Board, we retrospectively identified patients who had undergone iodine-125 seed localized lumpectomy at our institution from January 2010 to June 2017 by one of two fellowship-trained breast surgeons. Of those patients, a subset of 25 patients were identified who had undergone bracketed seed localization, defined as two or more seeds used to delineate the radiographic borders of the area of concern. All patients had originally presented with calcifications identified on screening mammogram that were subsequently diagnosed as ductal carcinoma in situ and/or invasive ductal carcinoma by image-guided biopsy performed at our institution. Eight patients had one positive margin on final surgical pathology and required re-excision (32%). One patient was converted to mastectomy. Of the patients requiring re-excision, the average maximum linear extent of calcifications was 3.4 cm (SD 0.97), whereas it was 3.1 cm (SD 1.2) in patients with negative surgical margins (P = 0.5). Bracketing calcifications with radioactive seeds can potentially allow more patients to undergo breast conservation surgery.}, } @article {pmid32161717, year = {2020}, author = {Guo, T and Chen, Z and Xu, J and Zhang, Y}, title = {Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {32}, pmid = {32161717}, issn = {2234-943X}, abstract = {Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.}, } @article {pmid32157060, year = {2019}, author = {Egawa, C and Yanai, A and Yanagawa, T and Takatsuka, Y and Takeno, A and Masuzawa, T and Hata, T and Kagawa, Y and Ohmura, Y and Katsura, Y and Murakami, K and Sakamoto, T and Kawai, K and Takeda, Y and Murata, K}, title = {[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2063-2065}, pmid = {32157060}, issn = {0385-0684}, mesh = {Adult ; *Brain Neoplasms/radiotherapy/secondary ; *Breast Neoplasms/radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; *Radiosurgery ; }, abstract = {A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.}, } @article {pmid32157013, year = {2019}, author = {Miyoshi, T and Yamaguchi, S and Shiobara, M and Wakatsuki, K and Suda, K and Miyazawa, K and Aida, T and Watanabe, Y and Yoneura, N and Yoshioka, S}, title = {[A New Projection-Marking Technique for Breast-Conserving Surgery Using a Radiation Treatment Planning System and Multi-Leaf Collimator in Patients with Breast Cancer-A Pilot Study].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {1922-1924}, pmid = {32157013}, issn = {0385-0684}, mesh = {*Breast Neoplasms/radiotherapy/surgery ; *Carcinoma, Intraductal, Noninfiltrating/radiotherapy/surgery ; Humans ; Mastectomy, Segmental ; Pilot Projects ; }, abstract = {In this study, a breast-conserving surgery(BCS)was performed involving the new image projection technique, using a radiation treatment planning system(RTPS)and a multi-leaf collimator(MLC), for patients with ductal carcinoma in situ (DCIS)and invasive ductal carcinoma(IDC)with ductal components. This study aimed to evaluate the feasibility of this procedure as a pilot study. From June 2014 to May 2017, 27 patients diagnosed with DCIS and IDC with ductal components underwent BCS. In the RTPS, the design of tumor resection was simulated, and the extent of resection was projected to the breast surface using the MLC. BCS was performed using this skin marking. Among 27 patients, 4(14.8%)had carcinoma in the surgical margins. As a pilot study, the simplicity and usefulness of this procedure was confirmed in BCS for patients with DCIS and IDC with ductal components. Further evaluation of its safety and efficacy will be conducted in more patients.}, } @article {pmid32156965, year = {2019}, author = {Kinoshita, H and Teraoka, H and Mori, T and Hasegawa, T and Noda, E and Takashima, T and Hirakawa, K and Ohira, M}, title = {[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2461-2463}, pmid = {32156965}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; Female ; Humans ; *Jaundice/etiology ; *Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel ; }, abstract = {A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.}, } @article {pmid32156942, year = {2019}, author = {Morisaki, T and Takashima, T and Asano, Y and Kashiwagi, S and Noda, S and Onoda, N and Ohira, M}, title = {[Two Cases of Orbital Metastasis from Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2392-2394}, pmid = {32156942}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms ; Eye Neoplasms/*secondary ; Female ; Humans ; *Liver Neoplasms ; Magnetic Resonance Imaging ; }, abstract = {Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.}, } @article {pmid32156921, year = {2019}, author = {Asano, Y and Kashiwagi, S and Kouhashi, R and Takada, K and Goto, W and Ishihara, S and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Advanced Breast Cancer with Altered Biology by Eribulin Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2330-2332}, pmid = {32156921}, issn = {0385-0684}, mesh = {*Breast Neoplasms/drug therapy ; Female ; Furans/*therapeutic use ; Humans ; Ketones/*therapeutic use ; Lymphatic Metastasis ; Middle Aged ; Tumor Microenvironment ; }, abstract = {In the treatment of advanced breast cancer, onlya few drugs confer overall survival(OS)benefit. Eribulin is a drug that was shown to extend OS in an international phase Ⅲtrial; however, the underlying mechanism is thought to involve cancer microenvironment regulation. The concept of "breast cancer subtype discordance" implies the biological changes that accompany treatment. Herein, we encountered a case of advanced breast cancer in a 54-year-old woman that showed biological changes after eribulin chemotherapy. The patient noticed a lump in her left breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonographyrevealed a large mass at the center of the left mammarygland and axillaryly mph node swelling. Core-needle biopsyconfirmed an invasive ductal carcinoma(ER stronglypositive, PgRnegative, HER-2 negative, Ki-67 low expression). CT findings showed multiple lung metastases. Letrozole was administered for cT4N2M1, stage Ⅳ, Luminal A, which showed progression to the left side with advances in breast cancer. Six months later, the primarytumor and axillaryly mph nodes showed progression. Subsequent treatment with eribulin was started, and partial response was obtained; however, new lymph node metastasis developed in the axilla after 11 cycles. The primary tumor and axillaryly mph nodes showed stronglypositive ER expression, were PgR-negative and HER2-positive, and showed Ki-67 low expression and HER2-positive conversion.}, } @article {pmid32156915, year = {2019}, author = {Sannomiya, H and Okamoto, T and Ryu, S and Ichikawa, J and Koreeda, N and Shin, Y and Yamana, I and Sato, K and Yoshida, Y and Noritomi, T and Yoshida, T and Hirata, K}, title = {[A Case of Small Cell Carcinoma of the Pancreas].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2312-2314}, pmid = {32156915}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Carcinoma, Small Cell/diagnostic imaging/drug therapy ; Cisplatin ; Humans ; Irinotecan ; Male ; Middle Aged ; *Pancreatic Neoplasms/diagnostic imaging/drug therapy ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 55-year-old man was admitted to our hospital for jaundice. Magnetic resonance cholangiopancreatography showed a mass in the pancreatic head as well as biliary obstruction. We strongly suspected invasive ductal carcinoma of the pancreas. We performed pancreaticoduodenectomy with partial resection of the portal vein. The histopathological diagnosis was small cell carcinoma of the pancreas. We detected metastasis of the right hilar lymph node in PET-CT scan performed 2 months after the surgery and started chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11). However, we observed recurrent metastasis of the right hilar lymph node 12 months after the surgery. We started second-line chemotherapy with amrubicin(AMR)and radiotherapy. Unfortunately, the patient died from multiple metastases of the left adrenal gland and brain 26 months after the surgery. The prognosis of small cell carcinoma of the pancreas is extremely poor. Multimodal treatment such as chemotherapy, radiotherapy, and curative operation are required for long-term survival.}, } @article {pmid32156914, year = {2019}, author = {Nakama, Y and Maruyama, Y and Hisaka, T and Yasumoto, M and Okabe, Y and Naito, Y and Yamaguchi, M and Tanaka, M and Tanaka, H and Akagi, Y and Okuda, K}, title = {[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2309-2311}, pmid = {32156914}, issn = {0385-0684}, mesh = {*Adenocarcinoma/secondary/surgery ; Adult ; *Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/secondary ; }, abstract = {A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.}, } @article {pmid32156893, year = {2019}, author = {Sugimoto, H and Miura, T and Kawamura, Y and Aburatani, T and Hanaoka, M and Ogo, T and Hoshino, N and Nishioka, Y and Kawano, T}, title = {[Case Report of Long-Term Clinical Efficacy of Paclitaxel plus Bevacizumab Combination Therapy for Stage Ⅳ AdvancedBreast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2246-2248}, pmid = {32156893}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; *Breast Neoplasms/drug therapy ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; Treatment Outcome ; }, abstract = {A 50-year-old woman had noted a mass in her right breast 2 years ago but did not consult a hospital. She consulted our hospital because the mass increased in size and also reddened. The tumor measured 10 cm in diameter and was palpable in the whole right breast. A core needle biopsy was performed, and invasive ductal carcinoma was diagnosed. CT showed multiple lung and liver metastases and bone scintigraphy showed bone metastases in a rib. Because the lung and liver metastases were life-threatening, paclitaxel(PTX)chemotherapy was administered weekly. Biomarkers analysis revealed ER(+), PgR(+), HER2(2+), HER2 FISH 1.27, Ki-67 30%, and bevacizumab (Bev) was added from 2 courses. After 4 courses of chemotherapy, the multiple lung and liver metastases were found to be significantly reduced on CT. Toxicities included alopecia, hypertension, and proteinuria. At this time, 3 years after the treatment started, PTX plus Bev combination therapy was also administered.}, } @article {pmid32156877, year = {2019}, author = {Fushimi, K and Kusashio, K and Yasutomi, J and Matsumoto, M and Suzuki, T and Iida, A and Imamura, N and Harano, R and Kosaki, R and Togasaki, K and Fujita, A and Udagawa, I}, title = {[Adenosquamous Carcinoma in the Remnant Pancreas after Pancreatoduodenectomy for Invasive Pancreas Cancer-A Resected Case with Five-Year Relapse-Free Survival].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2198-2200}, pmid = {32156877}, issn = {0385-0684}, mesh = {*Carcinoma, Adenosquamous/surgery ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/surgery ; Pancreaticoduodenectomy ; Time Factors ; }, abstract = {A 52-year-old man underwent pancreatoduodenectomy(PD)for invasive cancer of the pancreatic head, with a histopathological diagnosis of moderately to poorly differentiated invasive ductal carcinoma. One year and 2 months after PD, follow- up CT revealed a mass 3 cm in diameter in the remnant pancreas without distant metastasis. Therefore, total remnant pancreatectomy was performed with a histopathological diagnosis of adenosquamous carcinoma. Five years after re-excision, the patient remains alive without recurrence. Although no tumor component was found at the anastomotic site of the pancreatojejunostomy, squamous metaplasia with chronic inflammation with carcinogenic potential was diffusely observed in the main pancreatic duct. Clinical cases of remnant pancreatic resection after PD for invasive cancer are relatively rare. Furthermore, this case of adenosquamous carcinoma with long-term recurrence-free survival is extremely rare.}, } @article {pmid32156868, year = {2019}, author = {Sakakibara, J and Okubo, Y and Tanabe, N and Morita, Y and Nagashima, T and Ohtsuka, M}, title = {[Differences in Treatment Effect between Local and Distant Lesions in Breast Cancer Patients Administered Neoadjuvant Endocrine TherapyGuided byOncoty pe DX-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2170-2172}, pmid = {32156868}, issn = {0385-0684}, mesh = {Biopsy, Large-Core Needle ; *Breast Neoplasms/therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Receptors, Estrogen ; }, abstract = {We report different treatment effects between local and distant lesions based on oncotype DX in a patient with breast cancer administered neoadjuvant endocrine therapy. The patient was a 50-year-old woman. Ultrasound(US)showed a mass 16×11×11mm in diameter in the C area of her right breast. Histological examination revealed invasive ductal carcinoma positive for estrogen and progesterone receptor and negative for human epidermal growth factor receptor type 2(HER2), and a Ki-67 index of 38%. The recurrence score(RS)calculated from the core needle biopsy was 4(low-risk group)with a predicted 10-year risk of distant recurrence of 4% after 5 years of endocrine therapy. Oncotype DX showed that this patient would not benefit from chemotherapy. We administered neoadjuvant endocrine therapy. However, the tumor size increased to 26×18×15mm 1 month after treatment initiation. Therefore, right breast-conserving surgery and sentinel lymph node biopsy were performed. Histopathologically, the effect of the endocrine therapy was grade 0 and the surgical margins were negative. Even though RS was low in the breast, the effect of endocrine therapy differed between local and distant lesions such as circulating tumor cells.}, } @article {pmid32156862, year = {2019}, author = {Adachi, M and Sasaki, M and Ogawa, N and Kamiya, A and Matsunaga, H and Sugimoto, H and Koshiishi, H and Yoshimura, T}, title = {[A Case of Locally Advanced Breast Cancer Successfully Treated with Epirubicin/Cyclophosphamide].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {13}, pages = {2152-2154}, pmid = {32156862}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; Cyclophosphamide ; Epirubicin ; Female ; Humans ; Neoplasm Recurrence, Local ; }, abstract = {A 66-year-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass with bleeding. Triple-negative invasive ductal carcinoma of the breast was diagnosed by core needle biopsy. Computed tomogra- phy showed axillary and infraclavicular lymph node metastases. Epirubicin/cyclophosphamide(EC)therapy was started. We reduced the dose to 80%during courses 2-4. After 4 courses of treatment, CT showed a complete response. We reduced the dose to 50% during courses 5-12 and stopped chemotherapy. Five years have passed without recurrence since the first treatment.}, } @article {pmid32155777, year = {2020}, author = {Salvatorelli, L and Puzzo, L and Vecchio, GM and Caltabiano, R and Virzì, V and Magro, G}, title = {Ductal Carcinoma In Situ of the Breast: An Update with Emphasis on Radiological and Morphological Features as Predictive Prognostic Factors.}, journal = {Cancers}, volume = {12}, number = {3}, pages = {}, pmid = {32155777}, issn = {2072-6694}, abstract = {Ductal carcinoma in situ (DCIS) shows overlapping epidemiology with invasive ductal carcinoma of the breast, sharing similar risk factorssuch as age, mammographic density, family history, and hormonal therapy as well as genetic factors such as BRCA1/BRCA2, histotypes, and molecular subtypes such as luminal A and B, HER2 enriched, and basal-type, thus suggesting its potential precursor role. A small percentage of patients with a history of DCIS die without a documented intermediate diagnosis of invasive breast carcinoma (IBC). The increased risk of death is usually associated with ipsilateral recurrence such as IBC. The slightly variable incidence of DCIS in different countries is mainly due to a different diffusion of mammographic screening and variability of the risk factors. The majority of DCIS lesions are not palpable lesions, which can be only radiologically detected because of the association with microcalcifications. Mammography is a highly sensitive diagnostic procedure for detecting DCIS with microcalcifications, while magnetic resonance imaging (MRI) is considered more sensitive to detect DCIS without calcifications and/or multifocal lesions. The aim of the present overview was to focus on the clinical, radiological, and pathological features of DCIS of the breast, with an emphasis on the practical diagnostic approach, predictive prognostic factors, and therapeutic options.}, } @article {pmid32151023, year = {2020}, author = {Li, Z and Fan, M and Zhong, Z and Du, B}, title = {Coupling Effect of Molecular Chain Displacement and Carrier Trap Characteristics on DC Breakdown of HDPE/LDPE Blend Insulation.}, journal = {Polymers}, volume = {12}, number = {3}, pages = {}, pmid = {32151023}, issn = {2073-4360}, support = {51707133 and 51537008//National Natural Science Foundation of China/ ; 2016YFB0900701//National Key Research and Development Program of China/ ; }, abstract = {This work focuses on the coupling effect of molecular chain displacement and trap characteristics on direct current (DC) breakdown properties of high density/low density polyethylene (HDPE/LDPE) blend insulation. Frequency domain spectroscopy (FDS) and isothermal discharge current (IDC) are used to characterize the dielectric relaxation and trap characteristics of HDPE/LDPE blends. A DC breakdown model is proposed to reveal the mechanisms of the molecular chain displacement and carrier trap on the DC breakdown strength. The dielectric relaxation α and δ present segmental motions and thermal ion polarization behaviours of HDPE/LDPE blends, respectively. α dielectric relaxation strength (Δεα) increases as the amount of HDPE increases from 0 to 5 wt%, and then declines with a further increase of HDPE content to 20 wt%. According to the velocity equation, the increase of Δεα will increase the molecular chain displacement, resulting in a larger free volume, which will provide electrons with larger free path λ to form hot electrons. A positive correlation exists between the activation energy of the dielectric relaxation process δ and trap density, and the increase of δ dielectric relaxation strength (Δεδ) will adversely affect the breakdown strength of the specimen. HDPE/LDPE blends with 15 wt% HDPE content have lower Δεα and lowest Δεδ, which decreases the mean free path λ of molecular chain and thermal ion polarization. At the same time, it has the highest deep trap density, thus increasing the probability of hot electrons being captured and improving the DC breakdown strength. It is concluded the breakdown of the dielectric is synergistically affected by the molecular chain displacement and carrier trap.}, } @article {pmid32149793, year = {2020}, author = {Bernsen, MLE and van der Zant, FM and Wondergem, M and Broos, WAM and Knol, RJJ}, title = {Incidental Breast Carcinoma Detected With 13N-NH3 Cardiac PET Imaging.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {5}, pages = {e252-e253}, doi = {10.1097/RLU.0000000000002993}, pmid = {32149793}, issn = {1536-0229}, mesh = {Aged ; *Ammonia ; Breast Neoplasms/*diagnostic imaging ; Female ; Heart/*diagnostic imaging ; Humans ; *Incidental Findings ; Myocardial Perfusion Imaging ; *Nitrogen Radioisotopes ; *Positron Emission Tomography Computed Tomography ; }, abstract = {A 78-year-old woman with chest pain and a history of pacemaker implantation for arrhythmia underwent myocardial perfusion imaging by means of N-NH3 cardiac PET/CT. N-NH3 cardiac PET showed no signs of ischemia or infarction. Incidentally, a nodule with increased N-NH3 activity was observed in the right breast. Histopathologic examination revealed invasive ductal carcinoma.}, } @article {pmid32147980, year = {2020}, author = {Hoffman, A and Ben Ishay, O and Horesh, N and Shabtai, M and Forschmidt, E and Rosin, D and Gutman, M and Ram, E}, title = {Breast Cancer in Men: A Single Center Experience Over a Period of 22 years.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {22}, number = {3}, pages = {160-163}, pmid = {32147980}, issn = {1565-1088}, mesh = {Breast Neoplasms, Male/*epidemiology/*therapy ; Carcinoma, Ductal, Breast/*epidemiology/*therapy ; Disease-Free Survival ; Humans ; Israel/epidemiology ; Male ; Mastectomy/statistics & numerical data ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

OBJECTIVES: To review the experience with MBC of a single center in Israel over a period of 22 years.

METHODS: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993-2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

RESULTS: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A-2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2-178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

CONCLUSIONS: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.}, } @article {pmid32147641, year = {2021}, author = {Mori, N and Mugikura, S and Miyashita, M and Mori, Y and Maekawa, Y and Nagasaka, T and Takase, K}, title = {Turbo Spin-echo Diffusion-weighted Imaging Compared with Single-shot Echo-planar Diffusion-weighted Imaging: Image Quality and Diagnostic Performance When Differentiating between Ductal Carcinoma in situ and Invasive Ductal Carcinoma.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {20}, number = {1}, pages = {60-68}, pmid = {32147641}, issn = {1880-2206}, mesh = {Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal/*diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Echo-Planar Imaging/*methods ; Female ; Humans ; ROC Curve ; }, abstract = {PURPOSE: To compare the image quality between turbo spin-echo (TSE)-diffusion weighted imaging (DWI) and single-shot echo-planar imaging (EPI)-DWI, and to verify the diagnostic performance of the apparent diffusion coefficient (ADC) parameters of the two techniques by using histogram analysis in terms of differentiation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions.

METHODS: Ninety-four women with 94 lesions diagnosed as breast cancer by surgery underwent IRB-approved preoperative magnetic resonance imaging, including TSE and EPI-DWI with b-values of 50 and 850 s/mm[2]. Twenty lesions were identified as DCIS and 74 as IDC. Image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and geometric distortion] was evaluated quantitatively and compared between the TSE and EPI-DWI. A histogram analysis of the entire tumor voxel-based ADC data was performed, and the 10th, 25th, 50th, 75th, and 90th percentile values of each technique were compared between DCIS and IDC lesions.

RESULTS: The SNR and CNR of TSE-DWI were significantly higher than those of EPI-DWI (P < 0.0001 and < 0.0001). The geometric distortion of TSE-DWI was significantly lower than that of EPI-DWI (P < 0.0001). In TSE-DWI, the 10th, 25th, 50th, and 75th percentile values were significantly different between the DCIS and IDC lesions (P = 0.0010, 0.0004, 0.0008, and 0.0044, respectively). In EPI-DWI, the 50th and 75th percentile values were significantly different between the two groups (P = 0.0009 and 0.0093). There was no significant difference in the area under the curve of the receiver operating characteristic analysis of the 10th, 25th, 50th, and 75th percentile values of TSE-DWI, and the 50th and 75th percentile values of EPI-DWI (P = 0.29).

CONCLUSION: The image quality of TSE-DWI was better than that of EPI-DWI. DCIS lesions were distinguished from IDC lesions with a wider range of percentile values in TSE-DWI than in EPI-DWI, although diagnostic performance was not significantly different between the techniques.}, } @article {pmid32141170, year = {2020}, author = {Urbaniak, A and Jousheghany, F and Piña-Oviedo, S and Yuan, Y and Majcher-Uchańska, U and Klejborowska, G and Moorjani, A and Monzavi-Karbassi, B and Huczyński, A and Chambers, TC}, title = {Carbamate derivatives of colchicine show potent activity towards primary acute lymphoblastic leukemia and primary breast cancer cells-in vitro and ex vivo study.}, journal = {Journal of biochemical and molecular toxicology}, volume = {34}, number = {6}, pages = {e22487}, doi = {10.1002/jbt.22487}, pmid = {32141170}, issn = {1099-0461}, support = {2016/21/B/ST5/00111//Polish Science Centre/ ; //Arkansas Breast Cancer Research Program/ ; }, mesh = {Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/drug effects ; Carbamates/*pharmacology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colchicine/*analogs & derivatives/pharmacology ; Colchicum/chemistry ; Drug Screening Assays, Antitumor/methods ; Female ; Humans ; Inhibitory Concentration 50 ; MCF-7 Cells ; Middle Aged ; Plant Extracts/*pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*metabolism/pathology ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/*metabolism/pathology ; }, abstract = {Colchicine (COL) shows strong anticancer activity but due to its toxicity towards normal cells its wider application is limited. To address this issue, a library of 17 novel COL derivatives, namely N-carbamates of N-deacetyl-4-(bromo/chloro/iodo)thiocolchicine, has been tested against two types of primary cancer cells. These included acute lymphoblastic leukemia (ALL) and human breast cancer (BC) derived from two different tumor subtypes, ER+ invasive ductal carcinoma grade III (IDCG3) and metastatic carcinoma (MC). Four novel COL derivatives showed higher anti-proliferative activity than COL (IC50 = 8.6 nM) towards primary ALL cells in cell viability assays (IC50 range of 1.1-6.4 nM), and several were more potent towards primary IDCG3 (IC50 range of 0.1 to 10.3 nM) or MC (IC50 range of 2.3-9.1 nM) compared to COL (IC50 of 11.1 and 11.7 nM, respectively). In addition, several derivatives were selectively active toward primary breast cancer cells compared to normal breast epithelial cells. The most promising derivatives were subsequently tested against the NCI panel of 60 human cancer cell lines and seven derivatives were more potent than COL against leukemia, non-small-cell lung, colon, CNS and prostate cancers. Finally, COL and two of the most active derivatives were shown to be effective in killing BC cells when tested ex vivo using fresh human breast tumor explants. The present findings indicate that the select COL derivatives constitute promising lead compounds targeting specific types of cancer.}, } @article {pmid32140268, year = {2020}, author = {Choi, JE and Hyun, CL and Jin, MS and Lee, KM and Moon, JH and Ryu, HS}, title = {Downregulation of N-myc and STAT Interactor Protein Predicts Aggressive Tumor Behavior and Poor Prognosis in Invasive Ductal Carcinoma.}, journal = {Journal of breast cancer}, volume = {23}, number = {1}, pages = {36-46}, pmid = {32140268}, issn = {1738-6756}, abstract = {PURPOSE: We investigated the expression of the N-myc and STAT interactor (NMI) protein in invasive ductal carcinoma tissue and estimated its clinicopathologic significance as a prognostic factor. The expression levels and prognostic significance of NMI were also analyzed according to the molecular subgroup of breast cancers.

METHODS: Human NMI detection by immunohistochemistry was performed using tissue microarrays of 382 invasive ductal carcinomas. The correlation of NMI expression with patient clinicopathological parameters and prognostic significance was analyzed and further assessed according to the molecular subgroup of breast cancers. Moreover, in vitro experiments with 13 breast cancer cell lines were carried out. We also validated NMI expression significance in The Cancer Genome Atlas cohort using the Human Protein Atlas (HPA) database.

RESULTS: Low NMI expression was observed in 190 cases (49.7%). Low NMI expression was significantly associated with the "triple-negative" molecular subtype (p < 0.001), high nuclear grade (p < 0.001), high histologic grade (p < 0.001), and advanced anatomic stage (p = 0.041). Patients with low NMI expression had poorer progression-free survival (p = 0.038) than patients with high NMI expression. Low NMI expression was not significantly associated with patient prognosis in the molecular subgroup analysis. In vitro, a reduction of NMI expression was observed in 8 breast cancer cell lines, especially in the estrogen receptor-positive and basal B type of triple-negative breast cancer molecular subgroups. The HPA database showed that low NMI expression levels were associated with a lower survival probability compared with that associated with high NMI expression (p = 0.053).

CONCLUSION: NMI expression could be a useful prognostic biomarker and a potential novel therapeutic target in invasive ductal carcinoma.}, } @article {pmid32139710, year = {2020}, author = {Roy, S and Kumar, R and Mittal, V and Gupta, D}, title = {Classification models for Invasive Ductal Carcinoma Progression, based on gene expression data-trained supervised machine learning.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {4113}, pmid = {32139710}, issn = {2045-2322}, support = {SRF//Council of Scientific and Industrial Research (CSIR)/International ; SRF//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/PR6963/BID/7/427/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; BT/BI/25/066/2012//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; }, mesh = {Algorithms ; Breast Neoplasms/*classification/genetics ; Carcinoma, Ductal, Breast/*classification/genetics ; Databases, Genetic ; Datasets as Topic ; Early Detection of Cancer ; Female ; Gene Ontology ; Humans ; Machine Learning ; Microarray Analysis ; Models, Biological ; Neoplasm Staging ; Protein Interaction Maps ; RNA, Neoplasm ; RNA-Seq ; Reproducibility of Results ; *Supervised Machine Learning ; *Transcriptome ; }, abstract = {Early detection of breast cancer and its correct stage determination are important for prognosis and rendering appropriate personalized clinical treatment to breast cancer patients. However, despite considerable efforts and progress, there is a need to identify the specific genomic factors responsible for, or accompanying Invasive Ductal Carcinoma (IDC) progression stages, which can aid the determination of the correct cancer stages. We have developed two-class machine-learning classification models to differentiate the early and late stages of IDC. The prediction models are trained with RNA-seq gene expression profiles representing different IDC stages of 610 patients, obtained from The Cancer Genome Atlas (TCGA). Different supervised learning algorithms were trained and evaluated with an enriched model learning, facilitated by different feature selection methods. We also developed a machine-learning classifier trained on the same datasets with training sets reduced data corresponding to IDC driver genes. Based on these two classifiers, we have developed a web-server Duct-BRCA-CSP to predict early stage from late stages of IDC based on input RNA-seq gene expression profiles. The analysis conducted by us also enables deeper insights into the stage-dependent molecular events accompanying IDC progression. The server is publicly available at http://bioinfo.icgeb.res.in/duct-BRCA-CSP.}, } @article {pmid32138738, year = {2020}, author = {Sun, T and Yang, W and Toprani, SM and Guo, W and He, L and DeLeo, AB and Ferrone, S and Zhang, G and Wang, E and Lin, Z and Hu, P and Wang, X}, title = {Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {36}, pmid = {32138738}, issn = {1478-811X}, support = {R01 CA226981/CA/NCI NIH HHS/United States ; R03 CA216114/CA/NCI NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/administration & dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Cell Line, Tumor ; *Disulfiram/administration & dosage/pharmacology ; *Drug Repositioning ; Female ; Humans ; Immunogenic Cell Death/*drug effects ; Neoplastic Stem Cells ; Radiation Tolerance/*drug effects ; }, abstract = {BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.

METHODS: High aldehyde dehydrogenase activity (ALDH)[bright] and CD44[+]/CD24[-]/ESA[+] cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).

RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.

CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.}, } @article {pmid32135221, year = {2020}, author = {Shete, A and Kurle, S and Dhayarkar, S and Patil, A and Kulkarni, S and Ghate, M and Sangale, S and Medhe, U and Rajan, S and Verma, V and Gangakhedkar, R}, title = {High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.}, journal = {Microbial pathogenesis}, volume = {143}, number = {}, pages = {104117}, doi = {10.1016/j.micpath.2020.104117}, pmid = {32135221}, issn = {1096-1208}, mesh = {Adolescent ; Adult ; Anti-HIV Agents/*therapeutic use ; CD4-CD8 Ratio ; Drug Resistance, Viral/genetics ; Female ; HIV Infections/*drug therapy/virology ; Humans ; Interleukin-5/*blood ; Male ; Middle Aged ; Treatment Failure ; Viremia/blood/*drug therapy ; Young Adult ; }, abstract = {Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.}, } @article {pmid32132214, year = {2020}, author = {Lawrence, MG and Porter, LH and Clouston, D and Murphy, DG and Frydenberg, M and Taylor, RA and Risbridger, GP}, title = {Knowing what's growing: Why ductal and intraductal prostate cancer matter.}, journal = {Science translational medicine}, volume = {12}, number = {533}, pages = {}, doi = {10.1126/scitranslmed.aaz0152}, pmid = {32132214}, issn = {1946-6242}, mesh = {*Carcinoma, Intraductal, Noninfiltrating ; Humans ; Male ; *Prostatic Neoplasms ; }, abstract = {Prostate cancer is a common malignancy, but only some tumors are lethal. Accurately identifying these tumors will improve clinical practice and instruct research. Aggressive cancers often have distinctive pathologies, including intraductal carcinoma of the prostate (IDC-P) and ductal adenocarcinoma. Here, we review the importance of these pathologies because they are often overlooked, especially in genomics and preclinical testing. Pathology, genomics, and patient-derived models show that IDC-P and ductal adenocarcinoma accompany multiple markers of poor prognosis. Consequently, "knowing what is growing" will help translate preclinical research to pinpoint and treat high-risk prostate cancer in the clinic.}, } @article {pmid32119669, year = {2020}, author = {Rangel, GW and Clark, MA and Kanjee, U and Goldberg, JM and MacInnis, B and José Menezes, M and Ferreira, MU and Duraisingh, MT}, title = {Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.}, journal = {PLoS neglected tropical diseases}, volume = {14}, number = {3}, pages = {e0008104}, pmid = {32119669}, issn = {1935-2735}, support = {R01 AI140751/AI/NIAID NIH HHS/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Culture Media/chemistry ; Erythrocytes/*parasitology ; Female ; *Gene Expression Profiling ; *Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/*parasitology ; Male ; Parasitology/methods ; Plasmodium vivax/genetics/*growth & development ; Sequence Analysis, RNA ; }, abstract = {Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.}, } @article {pmid32116328, year = {2020}, author = {Ruiz-Esparza-Garrido, R and Torres-López, J and Piña-Sánchez, P and Viedma-Rodríguez, R and Rivera-González, A and Velázquez-Flores, MA}, title = {Expression changes of BIK in breast cancer tissues of different histological subtypes.}, journal = {Cirugia y cirujanos}, volume = {88}, number = {2}, pages = {163-169}, doi = {10.24875/CIRU.19001039}, pmid = {32116328}, issn = {2444-054X}, mesh = {Apoptosis Regulatory Proteins/*biosynthesis ; Breast Neoplasms/classification/*metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/*metabolism/*pathology ; Carcinoma, Lobular/classification/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; Mitochondrial Proteins/*biosynthesis ; Neoplasm Grading ; }, abstract = {OBJECTIVE: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer.

MATERIALS AND METHODS: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues).

RESULTS: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells.

CONCLUSIONS: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.}, } @article {pmid32116311, year = {2021}, author = {Veverkova, L and Melichar, B and Zlamalova, N and Vomackova, K and Koleckova, M and Thomas, RP}, title = {Association between negative preoperative axillary node staging and surgical sentinel node biopsy in patients with newly diagnosed breast cancer: A retrospective analysis.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {165}, number = {1}, pages = {64-68}, doi = {10.5507/bp.2020.005}, pmid = {32116311}, issn = {1804-7521}, mesh = {Axilla ; Breast Neoplasms/*pathology/surgery ; Female ; Humans ; Neoplasm Staging ; Preoperative Period ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; }, abstract = {AIM: The aim of this retrospective study was to analyse the preoperative ultrasound findings in patients with minimal or almost no morphological changes of axillary lymph nodes (LN) and to correlate these findings with the results of sentinel node (SN) biopsy.

MATERIALS AND METHODS: Between January 2014 and September 2018, 289 female patients with newly diagnosed breast cancer and negative preoperative axillary staging were examined with preoperative ultrasound evaluation of axillary LNs. Patients with no evidence of LN metastases underwent primary surgical treatment with SN biopsy. Negative predictive value (NPV) of preoperative ultrasound was evaluated and the histopathological findings in positive SN biopsies were correlated with tumour type and preoperative ultrasound LN imaging.

RESULTS: Of 289 patients with negative preoperative axillary staging who had primary surgical treatment, 268 patients had negative SN biopsy while SN metastases were detected in 21 patients. Of patients with positive SN biopsies, 2 patients had negative core biopsy of axillary LN before surgery. The preoperative ultrasound examination was negative in the remaining 19 patients with SN metastases.

CONCLUSIONS: Preoperative ultrasonography is very accurate in the detecting of axillary LN metastases. Patients with primary tumour size ≥ 1 cm, with grade ≥ 2 no special type carcinomas (NST - no special type, also known as invasive ductal carcinoma) or multicentric lobular invasive cancer should undergo a more thorough ultrasound evaluation.}, } @article {pmid32109199, year = {2021}, author = {Monfared, SS and Lebeau, JC and Mason, J and Cho, SK and Basevitch, I and Perry, I and Baur, DA and Tenenbaum, G}, title = {A Bio-Physio-Psychological Investigation of Athletes' Burnout.}, journal = {Research quarterly for exercise and sport}, volume = {92}, number = {1}, pages = {189-198}, doi = {10.1080/02701367.2020.1715911}, pmid = {32109199}, issn = {2168-3824}, mesh = {Adolescent ; Athletes/*psychology ; Blood Volume ; Burnout, Psychological/*psychology ; Emotions ; Female ; Galvanic Skin Response ; Humans ; Hydrocortisone/metabolism ; Male ; Respiratory Rate ; Saliva/metabolism ; Self Concept ; Youth Sports/psychology ; }, abstract = {Purpose: Changes in biophysiological markers related to perceived burnout and self-comfort were tested in this study. Method: Forty-two student-athletes from middle and high school grades were evaluated for burnout, salivary cortisol levels, measures of arousal-related physiological markers (i.e., blood volume pulse; BVP), galvanic skin response (GSR), and respiratory rate, and self-comfort variables during the last two weeks of the season. Using self-comfort theory as its conceptual framework, we examined burnout through a conceptual model in which feeling of discomfort with the self was related to biophysiological markers affecting perceived burnout. The proposed model was tested by using a partial least squares structural equation modeling (PLS-SEM). Results: The main findings indicate that increased self-discomfort is significantly (p < .001) associated with increased salivary cortisol (β = - 0.189) along with a significant (p = .050) decrease in GSR (β = - 0.259). Increased salivary cortisol is significantly (p < .001) associated with increased burnout (β = 0.242). Conclusion: The findings partially support the model and encourage further effort to capture the burnout syndrome through the integration of biological and psychological markers.}, } @article {pmid32108643, year = {2020}, author = {Kumarguru, BN and Ramaswamy, AS and Shaik, S and Karri, A and Srinivas, VS and Prashant, BM}, title = {Tumor budding in invasive breast cancer - An indispensable budding touchstone.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {Supplement}, pages = {S117-S122}, doi = {10.4103/IJPM.IJPM_731_18}, pmid = {32108643}, issn = {0974-5130}, mesh = {Adenocarcinoma/*pathology ; Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Histological Techniques ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/diagnosis/*pathology ; Middle Aged ; *Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Tertiary Care Centers ; Young Adult ; }, abstract = {BACKGROUND: Tumor budding denotes a phenomenon in which the tumor cells, singly or in small aggregates, become detached from the neoplastic glands at the invasive front of adenocarcinoma. Tumors with budding cells have a significantly more aggressive clinical course. Significance of tumor budding has mainly been examined in the field of colorectal cancer.

AIMS: To document the number tumor buds at the invasive front of invasive breast cancer. To correlate the number of tumor buds with other histopathological parameters, and available clinical details.

SETTING AND STUDY DESIGN: Analytical study at a rural tertiary care referral institute.

MATERIALS AND METHODS: It was a retrospective study of invasive breast cancer cases from January 2012 to April 2015. Tumor buds were counted in H and E stained sections in 10 High Power Fields (HPFs). Association of tumor budding with histological parameters and available clinical details were analyzed statistically.

STATISTICAL ANALYSIS USED: Frequencies, Chi-Square Test and Crosstabs were used for calculation.

RESULTS: 50 cases of invasive breast carcinoma were analyzed. Invasive ductal carcinoma constituted predominant histological type (92%). Low tumor budding (tumor buds ≤20/10HPFs) constituted 20 cases. High tumor budding (tumor buds >20/10HPFs) constituted 30 cases. Association of high tumor budding with lympho-vascular invasion, lymph node metastasis, primary tumor staging, regional lymph node staging, necrosis and Monckeberg medial sclerosis was statistically significant.

CONCLUSION: Tumor budding may be incorporated as a new parameter in reporting protocols. Tumor budding serves as an indispensable touchstone in evaluating cases of invasive breast cancer.}, } @article {pmid32103749, year = {2020}, author = {Tewari, SG and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {94}, pmid = {32103749}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI065853/NH/NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command/ ; }, mesh = {Erythrocytes/*metabolism/parasitology ; Malaria, Falciparum/*metabolism/parasitology ; Parasitemia/*metabolism/parasitology ; Plasmodium falciparum/*growth & development ; }, abstract = {BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.

METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.

RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.

CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.}, } @article {pmid32103597, year = {2020}, author = {Nakamura, R and Oyama, T and Inokuchi, M and Ishikawa, S and Hirata, M and Kawashima, H and Ikeda, H and Dobashi, Y and Ooi, A}, title = {The relation between anti-TGBFR1 immunohistochemical reaction and low Ki67, small tumor size and high estrogen receptor expression in invasive breast cancer.}, journal = {Pathology international}, volume = {70}, number = {6}, pages = {330-339}, doi = {10.1111/pin.12914}, pmid = {32103597}, issn = {1440-1827}, support = {//Smoking Research Foundation/ ; 16K07165//JSPS KAKENHI/ ; 16K08687//JSPS KAKENHI/ ; 17K08727//JSPS KAKENHI/ ; //The Hokkoku Cancer Foundation/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Middle Aged ; Receptor, Transforming Growth Factor-beta Type I/analysis/*metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {Most breast cancers are derived from the luminal epithelium, which composes the inside of the breast ductal structure. Ductal carcinoma in situ (DCIS) leads to invasive ductal carcinoma, but noncancerous intraductal proliferative lesions are also a risk factor for ductal carcinoma. The transforming growth factor beta (TGFB) signaling pathway behaves as a tumor suppressor in the early stage of cancer, and conversely as a tumor growth factor in invasive stages in several cancers. In this study, we performed immunohistochemistry with an antibody that detects the cytoplasmic region of TGFB receptor 1 (TGFBR1) and elucidated TGFBR1 protein expression in luminal epithelial cells of noncancerous breast ducts and in several cases of DCIS and invasive carcinoma. TGFBR1 expression was higher in noncancerous breast tissue than in cancerous tissue, and a difference in expression was also seen among histological subtypes. Comparing the expression level of TGFBR1 in cancer cells and clinico-pathological parameters, cases expressing low TGFBR1 tended to show low estrogen receptor expression, large tumor size (≥10 mm), and a high Ki67 labeling index. These data suggested that TGFBR1 protein expression may be related to the suppression of breast cancer cell growth.}, } @article {pmid32101644, year = {2020}, author = {Mohamed, KEH and Elamin, A}, title = {Adherence to endocrine therapy and its relation to disease-free survival among breast cancer patients visiting an out-patient clinic at Khartoum Oncology Hospital, Sudan.}, journal = {Journal of evaluation in clinical practice}, volume = {26}, number = {6}, pages = {1731-1743}, doi = {10.1111/jep.13373}, pmid = {32101644}, issn = {1365-2753}, mesh = {*Antineoplastic Agents, Hormonal/therapeutic use ; *Breast Neoplasms/drug therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Hospitals ; Humans ; Outpatients ; Sudan/epidemiology ; }, abstract = {RATIONALE: Adherence to endocrine therapy provides substantial reduction in breast cancer (BC) relapses and improve survival. Hence, non-adherence remains an under reported issue mainly in developing countries.

AIMS AND OBJECTIVES: The aim of this study is to evaluate the adherence to endocrine therapy (tamoxifen [TAM] and aromatase inhibitors [AIs]) among BC patients visiting an out-patient clinic (2015-2016) in Khartoum Oncology Hospital, Sudan.

METHODS: Adherence was assessed using pills count and self-reporting methods. A total of 172 patients were interviewed. Also, records were reviewed for demographic and other cancer characteristics.

RESULTS: The patients' mean age at diagnosis was 53 years, with the highest frequency at (41-60) years. Invasive ductal carcinoma 69.2% formed the main pathological diagnosis. T2 tumour size (51.2%) and lymph node involvement (N1) (31.4%) were most evident. Also, the majority of patients were stage III (45.9%) and grade II (48%). The studied women were postmenopausal (49.4%) and premenopausal (47.7%). Regarding hormonal receptors, about 68% were oestrogen (ER)+/progesterone (PR)+ and 23.3% were ER+/PR-. Studying adherence, almost (93%) of the studied group were ≥80% adherent to TAM and AIs. The hormonal therapy persistence mean was 27.2 ± 22.5 months (40-96). While adherence percentage mean was 93.7 ± 13.6% (0%-100%). Also disease-free survival (DFS) mean was 36.3 ± 32.7 months (4-312). Adherence to hormonal therapy and persistence were significantly correlated (P < .000). Also, statistically significant association was found between hormonal therapy adherence (≥80%) and patient poor to average economic status (P = .006), and the marital status "married" (P = .008).

CONCLUSIONS: A high rate of adherence (93%) to endocrine therapy was estimated in the present study. Also, a positive association was found between the hormonal therapy persistence, and the DFS year's groups (P = .000), and the hormonal therapy types (P = .000). Adherence to hormonal therapy and persistence were significantly correlated (P < .000).}, } @article {pmid32098687, year = {2020}, author = {Xu, Z and Shen, W and Pan, A and Sun, F and Zhang, J and Gao, P and Li, L}, title = {Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer.}, journal = {Pathology}, volume = {52}, number = {3}, pages = {329-335}, doi = {10.1016/j.pathol.2019.11.008}, pmid = {32098687}, issn = {1465-3931}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Fibroadenoma/pathology ; Humans ; Hyperplasia/pathology ; Middle Aged ; NIMA-Related Kinases/analysis/*biosynthesis ; Prognosis ; Young Adult ; }, abstract = {As a new member of Neks family, Nek9 regulates spindle assembly and controls chromosome alignment and centrosome separation. In the current study we aimed to investigate the expression of Nek9 in breast cancer and its clinical significance. We evaluated the expression of Nek9 in invasive ductal carcinoma (IDC, n=316), ductal carcinoma in situ (DCIS), usual ductal hyperplasia, atypical ductal hyperplasia, fibroadenoma and normal breast tissues using immunohistochemistry. The results revealed significantly reduced Nek9 in IDCs (41.8%) compared to benign breast lesions. Moreover, gradually reduced Nek9 was found from DCIS to invasive carcinoma and metastatic tumour within the same tumours. The decrease in Nek9 expression was associated with larger tumour size (p=0.0087), high grade (p<0.0001) and high Ki-67 index (p<0.0020). TCGA and GEO datasets analysis revealed low level of Nek9 mRNA was more frequent in triple negative breast cancers, and associated with poor overall survival and distant metastasis-free survival. These findings suggest an important role of Nek9 in the progression of breast cancer, and aberrantly expressed Nek9 correlates with more aggressive clinicopathological variables and predicts poor clinical prognosis. Nek9 may serve as a potential predictive factor for patients with breast cancer.}, } @article {pmid32095144, year = {2020}, author = {Kadivar, M and Aram, F}, title = {Assessment of Ki67 in Breast Cancer: A Comparison Between the Eye-10 Method, Stepwise Counting Strategy, and International System of Ki67 Evaluation.}, journal = {Iranian journal of pathology}, volume = {15}, number = {1}, pages = {13-18}, pmid = {32095144}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, such as the Eye-10 method and stepwise counting strategy, are proposed to facilitate measurement.

METHODS: Immunohistochemical staining of Ki67 was performed on 100 hormone-receptor-positive invasive ductal carcinoma specimens. Ki67LI was evaluated for each case, and then results were dichotomized by a cut-off point of 20%. Next, for each sample, an expert pathologist visually assessed percentages of Ki67-positive cells in 10% intervals at a glance (Eye-10 method). Finally, by using a dynamic process with rejection regions, Ki67 was defined so if the estimate belonged to the upper or lower rejection region, the Ki67 status had been determined and if the rejection region could not be reached after counting the maximum number of 400 tumor cells, the specimen was regarded as equivocal (stepwise counting strategy).

RESULTS: The comparison between Eye-10 and Ki67LI revealed almost perfect agreement (kappa coefficient =0.889), and the concordance between the stepwise counting strategy and Ki67LI was substantial (kappa coefficient =0.639).

CONCLUSION: Both two methods left some results in the gray/intermediate zone, which is unavoidable. Both methods are much faster and simpler than evaluation of Ki67LI and are also reliable. Regarding the gray zone in both methods, further improvements in the methodology, as well as more analytical studies, are needed.}, } @article {pmid32092496, year = {2020}, author = {Long, M and Verbeke, W and Ein-Dor, T and Vrtička, P}, title = {A functional neuro-anatomical model of human attachment (NAMA): Insights from first- and second-person social neuroscience.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {126}, number = {}, pages = {281-321}, doi = {10.1016/j.cortex.2020.01.010}, pmid = {32092496}, issn = {1973-8102}, mesh = {Anxiety Disorders ; Brain ; *Cognitive Neuroscience ; Humans ; Models, Anatomic ; Object Attachment ; }, abstract = {Attachment theory, developed by Mary Ainsworth and John Bowlby about seventy years ago, has become one of the most influential and comprehensive contemporary psychology theories. It predicts that early social interactions with significant others shape the emergence of distinct self- and other-representations, the latter affecting how we initiate and maintain social relationships across the lifespan. A person's attachment history will therefore associate with inter-individual differences in emotional and cognitive mechanisms sustaining representations, modeling, and understanding of others on the biological and brain level. This review aims at summarizing the currently available social neuroscience data in healthy participants on how inter-individual differences in attachment associate with brain anatomy and activity across the lifespan, and to integrate these data into an extended and refined functional neuro-anatomical model of human attachment (NAMA). We first propose a new prototypical initial attachment pathway and its derivatives as a function of attachment security, avoidance, and anxiety. Based on these pathways, we suggest a neural attachment system composed of two emotional mentalization modules (aversion and approach) and two cognitive mentalization modules (emotion regulation and mental state representation) and provide evidence on their functionality depending on inter-individual differences in attachment. We subsequently expand this first-person social neuroscience account by also considering a second-person social neuroscience perspective comprising the concepts of bio-behavioral synchrony and particularly inter-brain coherence. We hope that such extended and refined NAMA can inform attachment theory and ultimately help devising new prevention and intervention strategies for individuals and families at risk for attachment-related psychopathology.}, } @article {pmid32088208, year = {2020}, author = {Guillet, C and Rechsteiner, M and Bellini, E and Choschzick, M and Moskovszky, L and Dedes, K and Papassotiropoulos, B and Varga, Z}, title = {Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {64-73}, doi = {10.1016/j.humpath.2020.02.002}, pmid = {32088208}, issn = {1532-8392}, mesh = {Adult ; Age of Onset ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Heredity ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; *Mutation ; Papilloma/*genetics/pathology/surgery ; Pedigree ; Phenotype ; Proto-Oncogene Proteins c-akt/*genetics ; }, abstract = {Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.}, } @article {pmid32086991, year = {2020}, author = {Luo, Y and Kishi, S and Sasaki, T and Ohmori, H and Fujiwara-Tani, R and Mori, S and Goto, K and Nishiguchi, Y and Mori, T and Kawahara, I and Kondoh, M and Kuniyasu, H}, title = {Targeting claudin-4 enhances chemosensitivity in breast cancer.}, journal = {Cancer science}, volume = {111}, number = {5}, pages = {1840-1850}, pmid = {32086991}, issn = {1349-7006}, support = {17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; 16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Antibodies/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Claudin-1 ; Claudin-4/chemistry/genetics/*immunology ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Paclitaxel/pharmacology/therapeutic use ; Tamoxifen/pharmacology/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.}, } @article {pmid32083492, year = {2020}, author = {Amichai-Hamburger, Y and Mor, Y and Wellingstein, T and Landesman, T and Ophir, Y}, title = {The Personal Autonomous Car: Personality and the Driverless Car.}, journal = {Cyberpsychology, behavior and social networking}, volume = {23}, number = {4}, pages = {242-245}, doi = {10.1089/cyber.2019.0544}, pmid = {32083492}, issn = {2152-2723}, mesh = {Adult ; Automation ; Automobile Driving/*psychology ; *Automobiles ; Consumer Behavior ; Female ; Humans ; Male ; *Personality ; Regression Analysis ; Relational Autonomy ; Students/psychology ; Surveys and Questionnaires ; *User-Computer Interface ; Young Adult ; }, abstract = {Road traffic accidents, congestion and their ensuing issues are of international concern. A recent technological development to alleviate this situation is the autonomic car. A driverless vehicle will transport its passengers to their destinations. User experience would be enhanced by adapting the workings of the vehicle in line with the personality of its user. An autonomic car information system preference questionnaire was designed, focusing on different components of a futuristic information system. Participants comprised 155 students. The results demonstrated two factors: willingness to share information and need for control. A regression analysis on the automatic car preferences, personality (the Big 5), gender, and age showed that openness, consciousnesses, and age were related to different preferences. The results are assessed, followed by a discussion on personality in relation to the autonomic car.}, } @article {pmid32082666, year = {2020}, author = {Sarah, B and Ahmed, G and Saloua, B and Ibtissam, H and Abdeljalil, M and Maria, D and Anass, F and Hanane, R}, title = {Nodular Scleritis Revealing Metastasis of Breast Cancer: Diagnosis Not to Be Neglected.}, journal = {Case reports in ophthalmological medicine}, volume = {2020}, number = {}, pages = {8689463}, pmid = {32082666}, issn = {2090-6722}, abstract = {We report the case of ocular metastasis in a 48-year-old woman presenting left eye redness and pain. The patient was followed in another health institution for nodular scleritis and received systemic corticosteroids with moderate improvement. Medical history revealed that she was diagnosed three years ago with invasive ductal carcinoma of the left breast treated by tumorectomy with ganglion dissection. An ophthalmological examination found a hard scleral nodule with vascular architectural disorganization. A biopsy was performed, and the histopathological study revealed the presence of secondary tumor proliferation of poorly differentiated carcinoma of mammary cancer. This case report shows the fact that any unusual ocular presentation, even one simulating anterior scleritis, in a patient with a history of breast cancer should raise suspicion of metastasis.}, } @article {pmid32079470, year = {2020}, author = {Yin, S and Fan, Y and He, X and Wei, G and Wen, Y and Zhao, Y and Shi, M and Wei, J and Chen, H and Han, J and Jiang, L and Zhang, Q}, title = {The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.}, journal = {RNA biology}, volume = {17}, number = {6}, pages = {828-842}, pmid = {32079470}, issn = {1555-8584}, mesh = {Computational Biology/methods ; Erythrocytes/parasitology ; Exosome Multienzyme Ribonuclease Complex ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Ontology ; Humans ; Life Cycle Stages ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/*genetics/*growth & development ; *RNA Splicing ; RNA Stability ; RNA, Messenger/genetics ; RNA, Protozoan/*genetics ; RNA, Untranslated/genetics ; }, abstract = {The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.}, } @article {pmid32075583, year = {2020}, author = {Nissim, M and Livny, A and Barmatz, C and Tsarfaty, G and Berner, Y and Sacher, Y and Giron, J and Ratzon, NZ}, title = {Effects of aquatic physical intervention on fall risk, working memory and hazard-perception as pedestrians in older people: a pilot trial.}, journal = {BMC geriatrics}, volume = {20}, number = {1}, pages = {74}, pmid = {32075583}, issn = {1471-2318}, support = {Grant No. 3-13606//Ministry of Science and Technology, Israel/International ; }, mesh = {Accidental Falls/prevention & control ; Aged ; Aged, 80 and over ; Aging ; Exercise Therapy ; Female ; Gait ; Humans ; Male ; *Memory, Short-Term ; *Pedestrians ; Pilot Projects ; Postural Balance ; }, abstract = {BACKGROUND: Normal aging is associated with balance, mobility and working memory decline that increase fall risk and influence activity of daily living functions. Mounting evidence suggests that physical activity is beneficial for decreasing aging effects. Previous studies have focused on land-based physical activity. Research concerning the aquatic environment is scarce. The primary objectives of this three arm intervention pilot study were to examine the effects of an aquatic physical intervention program on balance, gait, fall risk and working memory among community-dwelling older individuals. The secondary objective was to examine the effects of an aquatic physical intervention program on safety of street-crossing among community-dwelling older individuals.

METHODS: Forty-two healthy participants aged 65 or older were enrolled into one of three intervention groups: aquatic physical intervention (API) (N = 13), on-land physical intervention (OLPI) (N = 14) or non-physical intervention (NPI) (N = 15). The intervention took place from 2018 until 2019 at Tel-Aviv University, Sheba medical center and Reich Center. The protocol included 30-min sessions twice a week for 12 weeks. Balance, gait and fall risk were assessed by the Tinneti test, working memory abilities were assessed by digit span and Corsi blocks tests and simulated safe streets-crossing was assessed by the hazard perception test for pedestrians. Testing and data collection was conducted at baseline, after six weeks and 12 weeks of intervention. All members of the professional team involved in evaluating participants were blind to the intervention group to which participants were allocated.

RESULTS: The differences in Tinetti balance (F (2, 39)=10.03, p < 0.01), fall risk (F (2, 39)=5.62, p0 > .05), digit span forward (F (2, 39)=8.85, p < 0.01) and Corsi blocks forward (F (2, 39)=3.54, p < 0.05) and backward (F (2, 39)=6.50, p < 0.05) scores after 12 weeks between the groups were significant. The API group showed improved scores. The differences in hazard perception test for pedestrians scores after 12 weeks of intervention between the groups were marginally significant (F (2, 39)=3.13, p = 0.055). The API group showed improved scores.

CONCLUSIONS: These findings may affect experts working with the elderly population when making decisions concerning therapeutic prevention interventions for the deficiencies of elderly patients. Older adults practicing aquatic physical activity could contribute to their increased safety.

TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov Registry NCT03510377. Date of registration: 10/31/2017.}, } @article {pmid32064280, year = {2020}, author = {Sarikaya, I and Sarikaya, A and Albatineh, AN and Tastekin, E and Sezer, YA}, title = {Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?.}, journal = {Asia Oceania journal of nuclear medicine & biology}, volume = {8}, number = {1}, pages = {27-35}, pmid = {32064280}, issn = {2322-5718}, abstract = {OBJECTIVES: Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases.

METHODS: FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted.

RESULTS: Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case.

CONCLUSION: In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.}, } @article {pmid32063604, year = {2020}, author = {Granados, K and Hüser, L and Federico, A and Sachindra, S and Wolff, G and Hielscher, T and Novak, D and Madrigal-Gamboa, V and Sun, Q and Vierthaler, M and Larribère, L and Umansky, V and Utikal, J}, title = {T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells.}, journal = {British journal of cancer}, volume = {122}, number = {7}, pages = {1023-1036}, pmid = {32063604}, issn = {1532-1827}, support = {OAICE-CAB-09-133-2015//Universidad de Costa Rica (University of Costa Rica)/International ; PED-054-2015-2//Ministerio de Ciencia Tecnología y Telecomunicaciones (Ministerio de Ciencia Tecnología y Telecomunicaciones de Costa Rica)/International ; 259332240 / RTG 2099//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; }, mesh = {Animals ; Calcium Channels, T-Type/*genetics ; Disease Models, Animal ; Female ; Humans ; Melanoma/*drug therapy/pathology ; Mice ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; Proto-Oncogene Mas ; }, abstract = {BACKGROUND: Drug resistance remains as one of the major challenges in melanoma therapy. It is well known that tumour cells undergo phenotypic switching during melanoma progression, increasing melanoma plasticity and resistance to mitogen-activated protein kinase inhibitors (MAPKi).

METHODS: We investigated the melanoma phenotype switching using a partial reprogramming model to de-differentiate murine melanoma cells and target melanoma therapy adaptation against MAPKi.

RESULTS: Here, we show that partially reprogrammed cells are a less proliferative and more de-differentiated cell population, expressing a gene signature for stemness and suppressing melanocyte-specific markers. To investigate adaptation to MAPKi, cells were exposed to B-Raf Proto-Oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors. De-differentiated cells became less sensitive to MAPKi, showed increased cell viability and decreased apoptosis. Furthermore, T-type calcium channels expression increased in adaptive murine cells and in human adaptive melanoma cells. Treatment with the calcium channel blocker mibefradil induced cell death, differentiation and susceptibility to MAPKi in vitro and in vivo.

CONCLUSION: In summary, we show that partial reprogramming of melanoma cells induces de-differentiation and adaptation to MAPKi. Moreover, we postulated a calcium channel blocker such as mibefradil, as a potential candidate to restore sensitivity to MAPKi in adaptive melanoma cells.}, } @article {pmid32062352, year = {2020}, author = {Kanwar, N and Carmine-Simmen, K and Nair, R and Wang, C and Moghadas-Jafari, S and Blaser, H and Tran-Thanh, D and Wang, D and Wang, P and Wang, J and Pasculescu, A and Datti, A and Mak, T and Lewis, JD and Done, SJ}, title = {Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis.}, journal = {EBioMedicine}, volume = {52}, number = {}, pages = {102646}, pmid = {32062352}, issn = {2352-3964}, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Calcium/metabolism ; Calcium Channels/chemistry/*genetics/metabolism ; Calcium Signaling ; Cell Line ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Progression ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Models, Biological ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Domains and Motifs ; }, abstract = {BACKGROUND: Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.

METHODS: In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these results in vivo.

FINDINGS: CACNG4 alters cell motility in vitro, induces malignant transformation in 3-dimensional culture, and increases lung-specific metastasis in vivo. CACNG4 functions by closing the channel pore, inhibiting calcium influx, and altering calcium signaling events involving key survival and metastatic pathway genes (AKT2, HDAC3, RASA1 and PKCζ).

INTERPRETATION: CACNG4 may promote homeostasis, thus increasing the survival and metastatic ability of tumour cells in breast cancer. Our findings suggest an underlying pathway for tumour growth and dissemination regulated by CACNG4 that is significant with respect to developing treatments that target these channels in tumours with aberrant calcium signaling.

FUNDING: Canadian Breast Cancer Foundation, Ontario; Canadian Institutes of Health Research.}, } @article {pmid32061163, year = {2020}, author = {Bartelt, A and Widenmaier, SB}, title = {Proteostasis in thermogenesis and obesity.}, journal = {Biological chemistry}, volume = {401}, number = {9}, pages = {1019-1030}, doi = {10.1515/hsz-2019-0427}, pmid = {32061163}, issn = {1437-4315}, mesh = {Humans ; Obesity/*physiopathology ; Proteostasis/*physiology ; Thermogenesis/*physiology ; }, abstract = {The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such as the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in concert to secure cellular proteostasis. In our modern society, the metabolic systems of the human body face the distinct challenge of changed diets, chronic overnutrition and sedentary lifestyles. Obesity and excess white adipose tissue accumulation are linked to a cluster of metabolic diseases and disturbed proteostasis is a common feature. Conversely, processes that promote energy expenditure such as exercise, shivering as well as non-shivering thermogenesis by brown adipose tissue (BAT) and beige adipocytes counteract metabolic dysfunction. Here we review the basic concepts of proteostasis in obesity-linked metabolic diseases and focus on adipocytes, which are critical regulators of mammalian energy metabolism.}, } @article {pmid32060782, year = {2020}, author = {Corona, SP and Bortul, M and Scomersi, S and Bigal, C and Bottin, C and Zanconati, F and Fox, SB and Giudici, F and Generali, D}, title = {Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers.}, journal = {Breast cancer research and treatment}, volume = {180}, number = {3}, pages = {735-745}, doi = {10.1007/s10549-020-05565-x}, pmid = {32060782}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/surgery ; Carcinoma, Lobular/*mortality/pathology/surgery ; Disease Management ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision/*mortality ; Mastectomy/*mortality ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*mortality ; Survival Rate ; Young Adult ; }, abstract = {INTRODUCTION: Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: 1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS).

RESULTS: 27.5% of patients with ILC had ≥ 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (p = 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15-19.5 p = 0.03), T3-T4 tumors (OR = 4.93, 95% CI 1.10-22.2, p = 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16-6.50, p = 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77-3.41, p = 0.20).

CONCLUSIONS: ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies.}, } @article {pmid32051475, year = {2020}, author = {Beetch, M and Harandi-Zadeh, S and Yang, T and Boycott, C and Chen, Y and Stefanska, B and Mohammed, SI}, title = {DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {2415}, pmid = {32051475}, issn = {2045-2322}, mesh = {Animals ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*veterinary ; *DNA Methylation ; Disease Progression ; Dog Diseases/*genetics/pathology ; Dogs/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/*veterinary ; }, abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast cancer unresponsive to traditional receptor-targeted treatments, leading to a disproportionate number of deaths. Invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DCIS). Detection of triple-negative DCIS (TN-DCIS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive TN-DCIS to invasive TNBC are needed. Here, we study a canine TN-DCIS progression and investigate the DNA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DCIS and invasive breast cancer. We report hypo- and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DNA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DCIS. Changes in DNA methylation during TN-DCIS progression in this canine model correspond with gene expression patterns in human breast tissues. This study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DCIS stage only of TN-DCIS progression.}, } @article {pmid32050925, year = {2020}, author = {Dettogni, RS and Stur, E and Laus, AC and da Costa Vieira, RA and Marques, MMC and Santana, IVV and Pulido, JZ and Ribeiro, LF and de Jesus Parmanhani, N and Agostini, LP and Dos Reis, RS and de Vargas Wolfgramm Dos Santos, E and Alves, LNR and Garcia, FM and Santos, JA and do Prado Ventorim, D and Reis, RM and Louro, ID}, title = {Potential biomarkers of ductal carcinoma in situ progression.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {119}, pmid = {32050925}, issn = {1471-2407}, support = {0468/2015//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66141494/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 66271126/2014//Fundação Estadual de Amparo à Pesquisa do Estado do Espírito Santo/ ; 0698/2015//Fundação de Amparo à Pesquisa do Espirito Santo-Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (FAPES-CAPES)/ ; }, mesh = {Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics/metabolism ; Computational Biology ; Disease Progression ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome ; }, abstract = {BACKGROUND: Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.

METHODS: In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.

RESULTS: The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.

CONCLUSIONS: We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.}, } @article {pmid32050826, year = {2020}, author = {Mostyka, M and Jessurun, J and Matrai, C}, title = {Sarcoid-Like Granulomatosis in a Patient With Breast Cancer Mimicking Refractory Metastatic Disease.}, journal = {International journal of surgical pathology}, volume = {28}, number = {6}, pages = {668-671}, doi = {10.1177/1066896920905887}, pmid = {32050826}, issn = {1940-2465}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Granuloma, Respiratory Tract/chemically induced/*pathology ; Humans ; Lung/pathology ; Pulmonary Fibrosis/chemically induced/pathology ; }, abstract = {Sarcoid-like granulomatosis is a known but rare adverse reaction to immune checkpoint inhibitors and chemotherapy in the treatment of advanced solid tumors. We present a case of a 29-year-old female with a pathologically confirmed poorly differentiated invasive ductal carcinoma of the breast with presumed metastases to the lungs, hilar lymph nodes, liver, and spleen. Despite appropriate chemotherapy, the patient developed pulmonary lesions that were interpreted on imaging studies as progression of malignancy. Autopsy revealed disseminated sarcoid-like granulomatosis with multiple noncaseating granulomata with associated fibrosis in the lungs, liver, and spleen. No residual invasive carcinoma or metastatic disease was identified. This case illustrates the difficulty in differentiating this nonneoplastic process from progressive disease in the clinical setting.}, } @article {pmid32047591, year = {2020}, author = {Burusapat, C and Buarabporn, N and Wongchansom, K and Chanapai, P and Parinyanut, P and Supaporn, S}, title = {Mammary adenoid cystic carcinoma presenting with Ductal carcinoma in situ and axillary lymph node metastasis.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {2}, pages = {rjz362}, pmid = {32047591}, issn = {2042-8812}, abstract = {Mammary adenoid cystic carcinoma (ACC) is extremely rare tumors, comprising <0.1% of all breast cancers. Moreover, lymph node metastasis is <2% of mammary ACC. Here, we report a case of 51-year-old female presented with painful mass on her left breast and left axillary lymph node enlargement. Core needle biopsy revealed invasive ductal carcinoma. Left lumpectomy and axillary lymph nodes dissections were performed. The final pathological report showed triple-negative mammary ACC arising with high grade ductal carcinoma in situ (DCIS) and axillary lymph node metastasis. Immunohistochemistry study is useful in confirming a diagnosis. Given the rarity of this cancer, natural history of disease is still not clearly understood. Complete surgical excision is the mainstay of treatment. To our best knowledge, mammary ACC presenting with DCIS and axillary lymph node metastasis has never been reported and should be considered in the differential diagnosis of breast cancers.}, } @article {pmid32047541, year = {2020}, author = {Moreno, AC and Lin, YH and Bedrosian, I and Shen, Y and Babiera, GV and Shaitelman, SF}, title = {Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes.}, journal = {Journal of Cancer}, volume = {11}, number = {6}, pages = {1341-1350}, pmid = {32047541}, issn = {1837-9664}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {Purpose: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods: We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%; P<0.001). Metaplastic BCs tended to be basal-like (77%), and relative to triple-negative or other BC, metaplastic BC was associated with higher clinical T status (cT3-4, 18% vs. 11%, 8%), no clinical nodal involvement (cN0, 86%, 77%, 80%), no lymphovascular invasion (72%, 65%, 62%), and high-grade tumors (71%, 77%, 35%) (P<0.001). Most metaplastic BCs were treated with mastectomy (58%), sentinel lymph node dissection (65%), chest wall or breast irradiation (74%), and chemotherapy (75%) as adjuvant therapy (60%). At a median follow-up time of 44.5 months, OS rates were lower for metaplastic BC than for triple-negative or other BC across all clinical stages at 5 years (stage I, 85%, 87%, 91%; II, 73%, 77%, 87%; III, 43%, 53%, 75%) and at 3 years (Stage IV, 15%, 22%, 64%; P<0.001). On multivariate analysis, increasing age, advanced clinical stage, lymphovascular invasion, axillary (vs. sentinel) node dissection, and no radiation or chemotherapy were associated with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC. Conclusion: Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC.}, } @article {pmid32047082, year = {2020}, author = {Kong, J and Shahait, AD and Kim, S and Choi, L}, title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast.}, journal = {BMJ case reports}, volume = {13}, number = {2}, pages = {}, pmid = {32047082}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/*surgery ; Female ; Humans ; Neoplasms, Radiation-Induced/*surgery ; Neoplasms, Second Primary/*surgery ; Sarcoma/*surgery ; }, abstract = {Breast sarcoma is a rare form of malignancy that arises from connective tissue within the breast, comprising less than 5% of all sarcomas. They develop as primary tumours or as secondary following radiation therapy. Diagnosis can be challenging as breast sarcomas are often asymptomatic and resemble benign breast tissue changes. Radiation-induced breast sarcomas present in various forms with an average latency period of 10-20 years following initial radiation therapy. Angiosarcomas are the most common form, while other types such as undifferentiated pleomorphic sarcomas remain rare. Here, we report a case of radiation-induced undifferentiated pleomorphic breast sarcoma in a 75-year-old woman that developed nearly 20 years following breast conserving surgery and radiation for invasive ductal carcinoma. The patient initially noticed a mass in 2017 on self-examination. The mammogram, ultrasound and biopsy at the time showed a benign 2.2 cm nodular fasciitis without malignancy. The mass grew rapidly in the next 6 months to 5.6 cm and repeat biopsy diagnosed undifferentiated pleomorphic sarcoma. The mass abutted the pectoralis muscle but staging workup ruled out distant metastasis and the patient underwent wide local resection of the mass with clear margins. The patient subsequently underwent further postoperative radiation due to insufficient posterior margin width on wide local excision, as chest wall resection would have been required for a wider posterior margin. Prognosis for postradiation sarcomas is generally poor with 27%-36% 5-year survival, with surgical resection as the main line of treatment. The patient currently remains disease-free after 15 months of surveillance.}, } @article {pmid32043593, year = {2020}, author = {Shahir, M and Mahmoud Hashemi, S and Asadirad, A and Varahram, M and Kazempour-Dizaji, M and Folkerts, G and Garssen, J and Adcock, I and Mortaz, E}, title = {Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells.}, journal = {Journal of cellular physiology}, volume = {235}, number = {10}, pages = {7043-7055}, pmid = {32043593}, issn = {1097-4652}, mesh = {Animals ; Biomarkers/metabolism ; Cell Communication/immunology ; Cell Proliferation/physiology ; Cells, Cultured ; Cytokines/immunology/metabolism ; Dendritic Cells/*immunology/metabolism ; Exosomes/*immunology/metabolism ; Female ; Immune Tolerance/*immunology ; Immunity/immunology ; Inflammation/immunology/metabolism ; Lymphocytes/immunology/metabolism ; Mesenchymal Stem Cells/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; }, abstract = {Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-β (TGF-β) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.}, } @article {pmid32042683, year = {2019}, author = {Lee, JS and Kim, JS and Lee, JH and Lee, JW and Lee, J and Park, HY and Yang, JD}, title = {Prepectoral breast reconstruction with complete implant coverage using double-crossed acellular dermal matrixs.}, journal = {Gland surgery}, volume = {8}, number = {6}, pages = {748-757}, pmid = {32042683}, issn = {2227-684X}, abstract = {BACKGROUND: Prepectoral implant-based breast reconstruction involving full implant coverage with an acellular dermal matrix (ADM) is more convenient, provides better aesthetic results, and carries lower risk of complications than does the traditional dual-plane method with an ADM. However, the recently reported technique usually involves full wrapping of the implant using a single, large ADM. We aimed to clarify the usefulness of an implant covering technique using two double-crossed ADMs.

METHODS: We retrospectively evaluated the records of 23 breast cancer patients who, between February 2017 and March 2018, received skin-sparing or nipple-sparing mastectomy followed by immediate prepectoral implant-breast reconstruction. We assessed preoperative characteristics, cancer treatment parameters, incidence of postoperative complications (necrosis, capsular contracture, infection), and patient satisfaction at 12 months postoperatively.

RESULTS: This cohort (mean age, 45.5 years; body mass index, 22.1 kg/m[2]; preoperative breast volume, 315.7 cc, excised mass weight, 291.4 g; silicone implant size, 252.4 cc) included 11 patients with ductal carcinoma in situ and 12 with invasive ductal carcinoma. Postoperatively, one patient received radiotherapy and nine received chemotherapy. Among postoperative complications, we noted capsular contracture (1/23, 4.3%), wound dehiscence (2/23, 8.7%), and seroma (3/23, 13.0%). Good patient satisfaction (mean score, 4.2-4.8 on the KNUH Breast Reconstruction Satisfaction Questionnaire) was obtained in all categories (breast symmetry, reconstructed breast size, shape, feel, pain, scar, self-confidence, sexual attractiveness, and overall satisfaction).

CONCLUSIONS: Prepectoral breast reconstruction involving complete implant coverage with double-crossed ADMs represents a good alternative to the traditional dual-plane subpectoral method, providing good patient satisfaction without adverse outcomes.}, } @article {pmid32042478, year = {2019}, author = {English, SW and Carabenciov, ID and Lehman, VT and Petty, GW and Scharf, EL}, title = {Zoster vasculopathy surveillance using intracranial vessel wall imaging.}, journal = {Neurology. Clinical practice}, volume = {9}, number = {6}, pages = {462-464}, pmid = {32042478}, issn = {2163-0402}, } @article {pmid32040672, year = {2020}, author = {Satpathy, G and Chandra, GK and Manikandan, E and Mahapatra, DR and Umapathy, S}, title = {Pathogenic Escherichia coli (E. coli) detection through tuned nanoparticles enhancement study.}, journal = {Biotechnology letters}, volume = {42}, number = {5}, pages = {853-863}, doi = {10.1007/s10529-020-02835-y}, pmid = {32040672}, issn = {1573-6776}, support = {IDC-water/16/2017//Indo-German Science and Technology Centre(IGSTC)/ ; }, mesh = {Anti-Bacterial Agents/chemistry/*pharmacology ; Cell Membrane Permeability ; Escherichia coli/drug effects/*isolation & purification/pathogenicity ; Escherichia coli Proteins/drug effects/metabolism ; Gold/chemistry/*pharmacology ; Metal Nanoparticles/chemistry ; Microbial Sensitivity Tests ; Microscopy, Fluorescence ; Surface Properties ; Zinc Oxide/chemistry/*pharmacology ; }, abstract = {OBJECTIVE: This study aims to detect pathogenic Escherichia coli (E. coli) bacteria using non-destructive fluorescence microscopy and micro-Raman spectroscopy.

RESULTS: Raman vibrational spectroscopy provides additional information regarding biochemical changes at the cellular level. We have used two nanomaterials zinc oxide nanoparticles (ZnO-NPs) and gold nanoparticles (Au-NPs) to detect pathogenic E. coli. The scanning electron microscope (SEM) with energy dispersive X-ray (EDAX) spectroscopy exhibit surface morphology and the elemental composition of the synthesized NPs. The metal NPs are useful contrast agents due to the surface plasmon resonance (SPR) to detect the signal intensity and hence the bacterial cells. The changes due to the interaction between cells and NPs are further correlated to the change in the surface charge and stiffness of the cell surface with the help of the fluorescence microscopic assay.

CONCLUSIONS: We conclude that when two E. coli strains (MTCC723 and MTCC443) and NPs are respectively mixed and kept overnight, the growth of bacteria are inhibited by ZnO-NPs due to changes in cell membrane permeability and intracellular metabolic system under fluorescence microscopy. However, SPR possessed Au-NPs result in enhanced fluorescence of both pathogens. In addition, with the help of Raman microscopy and element analysis, significant changes are observed when Au-NPs are added with the two strains as compared to ZnO-NPs due to protein, lipid and DNA/RNA induced conformational changes.}, } @article {pmid32038873, year = {2020}, author = {Crocker, C}, title = {Radiation-induced pemphigus in a patient with an invasive ductal carcinoma of the breast: a case report.}, journal = {Oxford medical case reports}, volume = {2020}, number = {1}, pages = {omaa001}, pmid = {32038873}, issn = {2053-8855}, abstract = {A 72-year-old woman with a known history of breast cancer was treated with adjuvant external beam radiation therapy. She initially developed radiation field localized blistering and erosions of the skin, before developing more widespread lesions. Immunofluorescence confirmed pemphigus vulgaris, which was responsive to corticosteroids. Pemphigus vulgaris is an autoimmune blistering disease of the skin that can rarely be associated with exposure to ionizing radiation.}, } @article {pmid32031117, year = {2020}, author = {Söyleyici, NA and Aslan, F and Avcýkurt, AS and Akgün, GA}, title = {Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {1}, pages = {19-24}, doi = {10.4103/IJPM.IJPM_658_19}, pmid = {32031117}, issn = {0974-5130}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/surgery ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Trans-Activators/*genetics ; Vascular Endothelial Growth Factor A/genetics ; }, abstract = {BACKGROUND: Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated.

METHODS: Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated.

RESULTS: In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF.

CONCLUSION: According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.}, } @article {pmid32031116, year = {2020}, author = {Varma, K and Chauhan, A and Bhargava, M and Misra, V and Srivastava, S}, title = {Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.}, journal = {Indian journal of pathology & microbiology}, volume = {63}, number = {1}, pages = {13-18}, doi = {10.4103/IJPM.IJPM_419_19}, pmid = {32031116}, issn = {0974-5130}, mesh = {Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; beta Catenin/*genetics ; }, abstract = {BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet.

MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association.

RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns.

CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.}, } @article {pmid32030367, year = {2019}, author = {Schwitzer, JA and Dekker, P and Kanuri, A and Tirrell, A and Sher, SR}, title = {Post-mastectomy radiation arteritis in a patient presenting with upper extremity claudication.}, journal = {AME case reports}, volume = {3}, number = {}, pages = {49}, pmid = {32030367}, issn = {2523-1995}, abstract = {Radiation arteritis is a rare but serious complication following radiation therapy for the treatment of breast cancer. We present the case of a 53-year-old female presenting with right upper extremity claudication 4 months following radiation therapy for the treatment of right breast cancer, stage 3b invasive ductal carcinoma. She was referred to vascular surgery and initial imaging with computed tomography angiography (CTA) revealed occlusion from the origin of the subclavian to axillary artery. We discuss the implications that these vascular findings have on potential breast reconstruction options.}, } @article {pmid32029810, year = {2020}, author = {Mohd Sobri, SN and Abdul Sani, SF and Sabtu, SN and Looi, LM and Chiew, SF and Pathmanathan, D and Chio-Srichan, S and Bradley, DA}, title = {Structural Studies of Epithelial Mesenchymal Transition Breast Tissues.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {1997}, pmid = {32029810}, issn = {2045-2322}, mesh = {Breast/pathology/surgery/*ultrastructure ; Breast Neoplasms/*pathology/surgery/ultrastructure ; Carcinoma, Ductal, Breast/*pathology/surgery/ultrastructure ; Collagen/ultrastructure ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Mastectomy ; Paraffin Embedding ; Retrospective Studies ; Scattering, Small Angle ; Synchrotrons ; Tissue Fixation/methods ; X-Ray Diffraction/instrumentation/methods ; }, abstract = {At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm[-1] and 1.5 nm[-1]. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9[th] and 10[th] order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.}, } @article {pmid32029638, year = {2020}, author = {Aminian, A and Zajichek, A and Arterburn, DE and Wolski, KE and Brethauer, SA and Schauer, PR and Nissen, SE and Kattan, MW}, title = {Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.}, journal = {Diabetes care}, volume = {43}, number = {4}, pages = {852-859}, pmid = {32029638}, issn = {1935-5548}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Bariatric Surgery/statistics & numerical data ; Computer Simulation ; Diabetes Complications/*diagnosis/epidemiology/pathology ; Diabetes Mellitus, Type 2/*complications/*diagnosis/epidemiology/*surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; *Machine Learning ; Male ; Middle Aged ; Organs at Risk/pathology ; Prognosis ; Retrospective Studies ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.

RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m[2] and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.

RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.

CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.}, } @article {pmid32020296, year = {2020}, author = {Kennedy, SA and Faughnan, ME and Vozoris, NT and Prabhudesai, V}, title = {Reperfusion of Pulmonary Arteriovenous Malformations Following Embolotherapy: A Randomized Controlled Trial of Detachable Versus Pushable Coils.}, journal = {Cardiovascular and interventional radiology}, volume = {43}, number = {6}, pages = {904-909}, doi = {10.1007/s00270-020-02422-8}, pmid = {32020296}, issn = {1432-086X}, mesh = {Arteriovenous Malformations/diagnostic imaging/*therapy ; Canada ; Embolization, Therapeutic/*instrumentation/*methods ; Equipment Design ; Female ; Fluoroscopy ; Humans ; Male ; Middle Aged ; Pulmonary Artery/*abnormalities/diagnostic imaging ; Pulmonary Veins/*abnormalities/diagnostic imaging ; Treatment Outcome ; }, abstract = {PURPOSE: To compare 1 year post-embolization reperfusion rates in pulmonary arteriovenous malformations (PAVMs) treated with the 0.035″ Interlock™ Fibered IDC™ Occlusion System coils (IDC) (Boston Scientific, Marlborough, Massachusetts) versus 0.035″ Nester coils (Cook Medical Inc., Bloomington, Indiana).

MATERIALS AND METHODS: A randomized controlled trial was performed randomizing individual PAVMs to treatment with IDC versus Nester coils at the largest hereditary hemorrhagic telangiectasia center in Canada. The primary outcome was CT evidence of reperfusion at 1 year. Secondary outcomes included periprocedural complications, fluoroscopy time and contrast volume.

RESULTS: Our study was terminated prematurely due to slow recruitment and subsequent expiration of funding. A total of 46 PAVMs in 25 patients (64% female) were included in our study; 26 randomized to Nester coils and 20 randomized to IDC. One patient was lost to follow-up. At a mean follow-up of 421.2 ± 215.7 days, no significant difference in PAVM reperfusion was detected between Nester coils and IDC (0% vs. 5.6%, p > 0.05). No major periprocedural complications were noted in either group. Fluoroscopy time (Nester: 15.0 ± 11.8 min vs. IDC 16.0 ± 5.4 min, p > 0.05) and contrast volume (Nester: 80.3 ± 36.5 ml vs. IDC 87.3 ± 51.7 ml, p > 0.05) utilized did not differ between groups.

CONCLUSION: No significant difference was detected in PAVM reperfusion rates, periprocedural complication rates, contrast volume utilization or fluoroscopy time following embolization with IDC and Nester coils.}, } @article {pmid32019280, year = {2020}, author = {Wu, J and Ding, S and Lin, L and Fei, X and Lin, C and Andriani, L and Goh, C and Huang, J and Hong, J and Gao, W and Zhu, S and Wang, H and Huang, O and Chen, X and He, J and Li, Y and Shen, K and Chen, W and Zhu, L}, title = {Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study.}, journal = {Cancer research and treatment}, volume = {52}, number = {3}, pages = {671-679}, pmid = {32019280}, issn = {2005-9256}, support = {81572581//National Natural Science Foundation of China/ ; 81772797//National Natural Science Foundation of China/ ; 14411950200//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 14411950201//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 16411966- 900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; 201840323//Grant of Shanghai municipal commission of health and family planning/ ; }, mesh = {Adenocarcinoma, Mucinous/metabolism/pathology/*therapy ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/metabolism/pathology/*therapy ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; China/epidemiology ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis/epidemiology/genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; *Transcriptome ; }, abstract = {PURPOSE: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).

MATERIALS AND METHODS: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.

RESULTS: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).

CONCLUSION: RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.}, } @article {pmid32016155, year = {2020}, author = {Tsay, AJ and Paine, AR and Lighthall, JG and Choi, KY and Hebel, J and Flamm, A}, title = {A possible pitfall of Mohs surgery in collision tumor diagnosis: A case of a squamous cell carcinoma of the scalp overlying a metastatic breast lesion of the skull.}, journal = {JAAD case reports}, volume = {6}, number = {2}, pages = {119-121}, pmid = {32016155}, issn = {2352-5126}, } @article {pmid32015927, year = {2020}, author = {Milne, DM and Sookar, N and Umakanthan, S and Rampersad, F and Olivier, L and Ali, J}, title = {Primary Osteosarcoma of the Breast in a Patient Treated Previously for Invasive Ductal Carcinoma: An Unusual Presentation of a Very Rare Primary Breast Malignancy.}, journal = {Case reports in surgery}, volume = {2020}, number = {}, pages = {1594127}, pmid = {32015927}, issn = {2090-6900}, abstract = {Primary osteogenic sarcoma of the breast is a rare clinical entity with few cases described in the literature. Unfortunately, the prognosis for these patients is poor when compared to invasive carcinomas of the breast. We report a case of a 58-year-old female who developed a primary osteogenic sarcoma of the breast five years after being treated for invasive carcinoma of the ipsilateral breast without the use of radiotherapy.}, } @article {pmid32010760, year = {2020}, author = {Scholl, AR and Flanagan, MB}, title = {Educational Case: Invasive Ductal Carcinoma of the Breast.}, journal = {Academic pathology}, volume = {7}, number = {}, pages = {2374289519897390}, pmid = {32010760}, issn = {2374-2895}, abstract = {The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.[1].}, } @article {pmid32007118, year = {2019}, author = {Komaei, I and Guccione, F and Sarra, F and Palmeri, E and Ieni, A and Cardia, R and Currò, G and Navarra, G and Palmeri, R}, title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.}, journal = {Il Giornale di chirurgia}, volume = {40}, number = {6}, pages = {544-550}, pmid = {32007118}, issn = {1971-145X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Diagnosis, Differential ; Epirubicin/administration & dosage ; Female ; Humans ; Letrozole/administration & dosage ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy ; Photons ; Radiotherapy, High-Energy/*adverse effects ; Sarcoma/diagnosis/*etiology/pathology/therapy ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.

CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.

CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.}, } @article {pmid32001164, year = {2020}, author = {Selvakumaran, V and Hou, R and Baker, JA and Yoon, SC and Ghate, SV and Walsh, R and Litton, TP and Lu, LX and Devalapalli, A and Kim, C and Soo, MS and Hwang, ES and Lo, JY and Grimm, LJ}, title = {Predicting Upstaging of DCIS to Invasive Disease: Radiologists's Predictive Performance.}, journal = {Academic radiology}, volume = {27}, number = {11}, pages = {1580-1585}, pmid = {32001164}, issn = {1878-4046}, support = {R01 CA185138/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/diagnostic imaging/surgery ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery ; Humans ; Mammography ; Neoplasm Invasiveness ; Radiologists ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: The purpose of this study is to quantify breast radiologists' performance at predicting occult invasive disease when ductal carcinoma in situ (DCIS) presents as calcifications on mammography and to identify imaging and histopathological features that are associated with radiologists' performance.

MATERIALS AND METHODS: Mammographically detected calcifications that were initially diagnosed as DCIS on core biopsy and underwent definitive surgical excision between 2010 and 2015 were identified. Thirty cases of suspicious calcifications upstaged to invasive ductal carcinoma and 120 cases of DCIS confirmed at the time of definitive surgery were randomly selected. Nuclear grade, estrogen and progesterone receptor status, patient age, calcification long axis length, and breast density were collected. Ten breast radiologists who were blinded to all clinical and pathology data independently reviewed all cases and estimated the likelihood that the DCIS would be upstaged to invasive disease at surgical excision. Subgroup analysis was performed based on nuclear grade, long axis length, breast density and after exclusion of microinvasive disease.

RESULTS: Reader performance to predict upstaging ranged from an area under the receiver operating characteristic curve (AUC) of 0.541-0.684 with a mean AUC of 0.620 (95%CI: 0.489-0.751). Performances improved for lesions smaller than 2 cm (AUC: 0.676 vs 0.500; p = 0.002). The exclusion of microinvasive cases also improved performance (AUC: 0.651 vs 0.620; p = 0.005). There was no difference in performance based on breast density (p = 0.850) or nuclear grade (p = 0.270) CONCLUSION: Radiologists were able to predict invasive disease better than chance, particularly for smaller DCIS lesions (<2 cm) and after the exclusion of microinvasive disease.}, } @article {pmid31995336, year = {2020}, author = {Knowles, S and Maxwell, J and Lumsden, A and Pearson, L and Pulhin, J and McLean, J and Brackstone, M and Hanrahan, R}, title = {An alternative to standard lumpectomy: a 5-year case series review of oncoplastic breast surgery outcomes in a Canadian setting.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {63}, number = {1}, pages = {E46-E51}, pmid = {31995336}, issn = {1488-2310}, mesh = {Breast Neoplasms/*pathology/*surgery/therapy ; Female ; Humans ; Margins of Excision ; Mastectomy, Segmental/*methods/standards ; Ontario ; Retrospective Studies ; Tertiary Care Centers ; }, abstract = {BACKGROUND: Oncoplastic surgery (OPS) is becoming the new standard of care for breast-conserving surgery (BCS). It has become increasingly popular in Europe; however, it has not yet been widely accepted in North America. This study aims to describe the experience with OPS at a Canadian tertiary care centre.

METHODS: This study is a retrospective case series consisting of consecutive OPS cases at a single Canadian centre, the Royal Victoria Regional Health Centre in Barrie, Ontario, between 2009 and 2015.

RESULTS: A total of 275 women who consecutively underwent OPS were included. The average size of the tumour was 17 mm (standard deviation [SD] 13 mm; range 0–110 mm). The average specimen weight was 155 g (SD 146 g; range 15–1132 g). Invasive ductal carcinoma was the most common diagnosis (237 patients, 86.2%), followed by ductal carcinoma in situ (18 patients, 6.6%) and then invasive lobular carcinoma (15 patients, 5.5%). A positive margin was recorded in 37 (13.5%) patients. Immediate postoperative complications included seroma and edema (32.7%), wound infection (13.1%), hematoma (8.7%) and delayed wound healing (6.5%). A delay to adjuvant therapy due to postoperative complications occurred in 7 of 217 (3.2%) patients. The median follow-up was 18 months. There were local and distant recurrences in 9 (3.3%) and 2 (0.7%) patients, respectively. Overall survival was 99.3%.

CONCLUSION: The findings of this study are comparable to results in the literature on OPS and demonstrate that OPS is an attractive alternative to standard lumpectomy for Canadian general surgeons who treat breast cancer.}, } @article {pmid31992198, year = {2020}, author = {Assefa, T and Zhang, J and Chowda-Reddy, RV and Moran Lauter, AN and Singh, A and O'Rourke, JA and Graham, MA and Singh, AK}, title = {Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.}, journal = {BMC plant biology}, volume = {20}, number = {1}, pages = {42}, pmid = {31992198}, issn = {1471-2229}, support = {NA//Iowa Soybean Association/ ; NA//Iowa State University/ ; NA//North Central Soybean Research Program (US)/ ; NA//Agricultural Research Service/ ; NA//National Institute of Food and Agriculture/ ; }, mesh = {Epistasis, Genetic ; Gene Expression Profiling ; Genes, Plant ; Genome, Plant ; *Genome-Wide Association Study ; Iron/*metabolism ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Seed Bank ; Soybeans/*genetics ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.

RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.

CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.}, } @article {pmid31992119, year = {2020}, author = {Billena, C and Padia, S and O'Brien, B and Knoble, J and Gokhale, A and Rajagopalan, M}, title = {Radiation recall dermatitis after treatment of stage IV breast cancer with nivolumab: a case report.}, journal = {Immunotherapy}, volume = {12}, number = {2}, pages = {123-130}, doi = {10.2217/imt-2019-0020}, pmid = {31992119}, issn = {1750-7448}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*drug therapy/*radiotherapy ; Female ; Humans ; Nivolumab/*therapeutic use ; Radiodermatitis/complications/*etiology ; Radiotherapy, Adjuvant ; }, abstract = {Radiation recall dermatitis (RRD) is an uncommon dermatologic reaction provoked notably by chemotherapy in an area of skin irradiated weeks to years prior. We report a case of RRD with nivolumab in a woman with breast cancer. The patient was diagnosed with invasive ductal carcinoma of the left breast with an isolated spinal metastasis approached in an oligometastatic fashion with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant radiotherapy. Unfortunately, after progression of bony metastases treated with radiotherapy, the patient received nivolumab and subsequently developed a rash corresponding to the adjuvant radiation field. This case highlights the unpredictable nature and characteristic rash of RRD. It is an important differential diagnosis for multidisciplinary teams who also see chemotherapy-induced dermatitis and immune-related adverse events.}, } @article {pmid31989433, year = {2020}, author = {Bishop, JA and Gagan, J and Krane, JF and Jo, VY}, title = {Low-grade Apocrine Intraductal Carcinoma: Expanding the Morphologic and Molecular Spectrum of an Enigmatic Salivary Gland Tumor.}, journal = {Head and neck pathology}, volume = {14}, number = {4}, pages = {869-875}, pmid = {31989433}, issn = {1936-0568}, mesh = {Aged ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Salivary Gland Neoplasms/*pathology ; }, abstract = {Intraductal carcinoma (IDC) is the current designation for a salivary gland neoplasm previously referred to as "low-grade salivary duct carcinoma" and "low-grade cribriform cystadenocarcinoma," among others. IDC is conceptually believed to be similar to ductal carcinoma in-situ of the breast. Although IDC is one entity in the current WHO Classification of Head and Neck Tumors, recent studies have suggested that at least three subtypes exist: a low-grade, intercalated duct-like variant with frequent RET rearrangements; a high-grade apocrine variant with complex, salivary duct carcinoma-like genetics; and a mixed variant. We sought to characterize an unusual form of low-grade, purely apocrine IDC. Three cases of apocrine-type IDC with low-grade histology were retrieved from the authors' consultation files. Immunohistochemistry for androgen receptor, GCDFP-15, S100, smooth muscle actin, and p40 was performed. A custom, targeted next generation sequencing (NGS) panel including 1425 cancer-related genes was also done on all cases. All three cases developed in the parotid glands of men, aged 51, 63, and 73 years (mean, 62 years). All cases consisted of large, rounded macrocysts surrounded by smaller nests which were lined by cells with abundant granular eosinophilic cytoplasm and large round nuclei with prominent nucleoli. Pleomorphism was mild, the mitotic rate was low, and necrosis was absent. No cases had any invasive foci or areas of intercalated duct-like morphology. By immunohistochemistry, all cases were diffusely positive for androgen receptor and GCDFP-15, surrounded entirely by an intact layer of small myoepithelial cells positive for S100, smooth muscle actin, and p40. Targeted NGS results were obtained from two cases: both harbored HRAS mutations and copy number losses in TP53, while one case each harbored mutations in PIK3CA, SPEN, and ATM. Fusions were absent in both cases. All three patients were treated by surgery alone, and are currently free of disease (follow up 12-190 months). This study confirms the existence of a low-grade, purely apocrine form of IDC. In its pure form, i.e., without an intercalated duct-type component, low-grade apocrine IDC is genetically similar to high-grade salivary duct carcinoma, with frequent HRAS and PI3K pathway mutations. Despite its molecular similarities to the aggressive salivary duct carcinoma, low-grade apocrine IDC appears to behave in a very indolent manner, supporting is classification as a non-invasive neoplasm, and underscoring the need to distinguish these tumors from each other.}, } @article {pmid31980982, year = {2020}, author = {Zhao, Y and Wang, Y and Zhu, F and Zhang, J and Ma, X and Zhang, D}, title = {Gene expression profiling revealed MCM3 to be a better marker than Ki67 in prognosis of invasive ductal breast carcinoma patients.}, journal = {Clinical and experimental medicine}, volume = {20}, number = {2}, pages = {249-259}, pmid = {31980982}, issn = {1591-9528}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/therapy ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*genetics ; Middle Aged ; Minichromosome Maintenance Complex Component 3/*genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; }, abstract = {Invasive ductal carcinoma (IDC) is the most common breast cancer. Our study used gene microarray data to select differentially expressed genes between normal and IDC mammary tissues. From these, we selected genes related to the proliferation of tumor cells and compared their prognostic value with known biomarker Ki67 for IDC. Analysis of publicly available Gene Expression Omnibus (GEO) data revealed 24 differentially expressed genes (DEGs) in normal and 31 DEGS in IDC tissues that were used for further analyses. Gene chip analysis software was used to identify DEGs. DEG profiles were confirmed using quantitative PCR (qPCR). DEG functions where shown to be related to cell proliferation. We confirmed MCM3 expression using immunohistochemical staining in 45 IDC patients. The relationship between MCM3 expression and survival was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models. A total of 1307 differentially expressed genes were identified between IDC and normal tissues, which were enriched in 32 Gene Ontology (GO) terms and 9 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. qPCR demonstrated that both COL1A1 and MCM3 were significantly up-regulated in IDC tissues, of which only MCM3 was related to cell proliferation. Ki67 is closely associated with the tumor grade, ER status, PR status and HER2 status, while MCM3 was shown to relate to tumor size, lymph node, and PR status. There was significant association between survival and MCM3, but not for Ki67. High MCM3 expression demonstrated statistically significant associations with poor prognosis in IDC patients. Findings from the gene microarray data analysis confirmed that MCM3 is associated with the response to cell proliferation. MCM3 represents a better proliferation marker than Ki67 making it a valuable prognostic tool that is independent of ER and HER2 status.}, } @article {pmid31979977, year = {2020}, author = {González-Huebra, I and Malmierca, P and Elizalde, A and Etxano, J and Vejborg, I and Uhlenbrock, D and Pina, L}, title = {The accuracy of titanium contrast-enhanced mammography: a retrospective multicentric study.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {61}, number = {10}, pages = {1335-1342}, doi = {10.1177/0284185119900440}, pmid = {31979977}, issn = {1600-0455}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Mammography/*instrumentation ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Titanium/*chemistry ; }, abstract = {BACKGROUND: Recently, a new mammography system to perform contrast-enhanced mammography has become available in the market. For the high-energy acquisition, it uses a titanium filter instead of a copper one, reducing the tube load while maintaining image quality.

PURPOSE: To retrospectively evaluate the accuracy of contrast-enhanced mammography with a titanium filter (TiCEM) in three readers with different grades of experience.

MATERIAL AND METHODS: IRB-approved retrospective multicentric lesion by lesion study with 200 lesions, all of them initially classified as BI-RADS categories 0/3/4/5 on mammography and/or ultrasound and with pathological confirmation, in 135 patients. Three readers with different levels of experience (expert, resident, intermediate) blinded to the final diagnosis, retrospectively evaluated the low-energy (LE) images and the combination of LE and recombined (subtracted) images and classified the lesions according to the BI-RADS categories. Reader 1 also categorized the breast density. ROC curves were performed for each reader.

RESULTS: Out of the 200 lesions, 82 were benign and 118 malignant (20 DCIS, 10 ILC, 88 IDC). The AUCs of LE versus TiCEM for were: Reader 1: 0.7 vs. 0.88, P < 0.001; Reader 2: 0.63 vs. 0.83, P < 0.001; and Reader 3: 0.63 vs. 0.84, P < 0.001. For the three readers, the AUCs of LE versus TiCEM were significantly superior in both dense and non-dense breasts (P < 0.001). Comparing the AUC of LE for Reader 1 (expert) versus the AUC of TiCEM for Reader 2 (resident) there were significant differences (0.7 vs. 0.83, P < 0.001).

CONCLUSION: The accuracy of TiCEM was significantly better for all the readers, in both dense and non-dense breasts. The accuracy of a resident reading a TiCEM study was better than the accuracy of an expert radiologist reading LE images.}, } @article {pmid31973658, year = {2020}, author = {Nagar, M and Nakash, O and Westen, D}, title = {Unpacking childhood experiences of abuse: Can clinicians identify their patients' History of Abuse?.}, journal = {Journal of trauma & dissociation : the official journal of the International Society for the Study of Dissociation (ISSD)}, volume = {21}, number = {3}, pages = {396-408}, doi = {10.1080/15299732.2020.1719264}, pmid = {31973658}, issn = {1529-9740}, mesh = {Adolescent ; Adult ; Adult Survivors of Child Abuse/*psychology ; Aged ; Female ; Humans ; Israel ; Male ; Mental Disorders/*diagnosis ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {Emotional, physical and sexual abuse, have been consistently linked to mental health problems in adults. Previous research found that mental health providers rarely ask their patients about their childhood experiences of abuse. No study to date has examined the convergence of clinicians' and patients' reports of childhood abuse. The current study applied a multi-method, multi-informant approach to explore the concordance between patients' reports of childhood experiences of abuse and clinicians' identification of their patients' history of abuse. Assessment of an independent interviewer was included. A convenience sample of clinicians (N = 80) and their patients (N = 170) in mental health clinics in care-as-usual settings participated in the study. To assess the history of abuse clinicians and patients completed the Clinical Data Form, patients additionally completed the Childhood Trauma Questionnaire. Independent interviewer completed the Familial Experiences Interview. Findings show that across all informants, exposure to emotional abuse was most prevalent, followed by physical abuse and least prevalent was sexual abuse. Additionally, clinicians reported lower prevalence of physical and sexual abuse among their patients as compared with the patient and independent interviewer's reports. Moderate to strong correlations were observed between clinicians, patients and independent interviewer reports of emotional, physical and sexual childhood abuse. Moreover, the severity of the patient's history of abuse was related to greater accuracy in clinicians' reports. Clinicians are advised to collect explicit information regarding childhood abuse through interviews or valid measures. Clinicians should pay special attention when assessing patients with moderate severity of childhood abuse since they are frequently under-identified.}, } @article {pmid31953417, year = {2020}, author = {Dai, D and Shi, R and Wang, Z and Zhong, Y and Shin, VY and Jin, H and Wang, X}, title = {Competing Risk Analyses of Medullary Carcinoma of Breast in Comparison to Infiltrating Ductal Carcinoma.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {560}, pmid = {31953417}, issn = {2045-2322}, mesh = {Adult ; Age Distribution ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Medullary/mortality/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Models, Theoretical ; *Nomograms ; Prognosis ; Risk Assessment ; SEER Program ; Socioeconomic Factors ; Tumor Burden ; Young Adult ; }, abstract = {The aim of current study was to use competing risk model to assess whether medullary carcinoma of the breast (MCB) has a better prognosis than invasive ductal carcinomas of breast cancer (IDC), and to build a competing risk nomogram for predicting the risk of death of MCB. We involved 3,580 MCB patients and 319,566 IDC patients from Surveillance, Epidemiology, and End Results (SEER) database. IDC was found to have a worse BCSS than MCB (Hazard ratio (HR) > 1, p < 0.001). The 5-year cumulative incidences of death (CID) was higher in IDC than MCB (p < 0.001). Larger tumor size, increasing number of positive lymph nodes and unmarried status were found to worsen the BCSS of MCB (HR > 1, p < 0.001). We found no association between ER, PR, radiotherapy or chemotherapy and MCB prognosis (p > 0.05). After a penalized variable selection process, the SH model-based nomogram showed moderate accuracy of prediction by internal validation of discrimination and calibration with 1,000 bootstraps. In summary, MCB patients had a better prognosis than IDC patients. Interestingly, unmarried status in addition to expected risk factors such as larger tumor size and increasing number of positive lymph nodes were found to worsen the BCSS of MCB. We also established a competing risk nomogram as an easy-to-use tool for prognostic estimation of MCB patients.}, } @article {pmid31941968, year = {2020}, author = {Elmetwali, T and Salman, A and Wei, W and Hussain, SA and Young, LS and Palmer, DH}, title = {CD40L membrane retention enhances the immunostimulatory effects of CD40 ligation.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {342}, pmid = {31941968}, issn = {2045-2322}, mesh = {Antigens, CD/metabolism ; Antigens, Neoplasm/metabolism ; Apoptosis/drug effects ; CD40 Antigens/metabolism ; CD40 Ligand/genetics/*metabolism/pharmacology ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Line, Tumor ; Cell Membrane/*metabolism ; Cell Proliferation ; Dendritic Cells/cytology/immunology/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Genetic Vectors/genetics/metabolism ; Humans ; Immunoglobulins/metabolism ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Leukocytes, Mononuclear/cytology/metabolism ; Membrane Glycoproteins/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism ; Urinary Bladder Neoplasms/immunology/metabolism/pathology ; }, abstract = {In carcinomas, the nature of CD40 ligand shapes the outcome of CD40 ligation. To date, the consequences of membrane-bound CD40L (mCD40L) on its immune-stimulatory function are unknown. Here, we examined the impact of mCD40L versus soluble CD40L (sCD40L) on T24 bladder carcinoma gene expression profiling. Of 410 differentially expressed genes, 286 were upregulated and 124 downregulated by mCD40L versus sCD40L. Gene ontology enrichment analysis revealed immune-stimulatory function as the most significant enriched biological process affected by upregulated transcripts, while those downregulated were critical for cell growth and division. Furthermore, immature dendritic cells (iDC) responded to mCD40L with enhanced maturation and activation over sCD40L evidenced by higher expression levels of CD83, CD86, HLA-DR and CD54, increased secretion of IL12 and IL10 and higher tumour-antigen (TA) uptake capacity. Furthermore, autologus CD3+ T cells responded to TA-loaded mCD40L-activated DC with increased proliferation and cytotoxic response (CD107a and IFN-γ-producing CD3+ CD8+ T cells) to the tumour-loaded autologous PBMCs compared to sCD40L. Thus, these data indicate that mCD40L enhances the immunostimulatory capacity over sCD40L. Furthermore, the ability of mCD40L to also directly induce cell death in CD40-expressing carcinomas, subsequently releasing tumour-specific antigens into the tumour microenvironment highlights the potential for mCD40L as a multi-faceted anti-cancer immunotherapeutic.}, } @article {pmid31939699, year = {2020}, author = {Volterrani, L and Gentili, F and Fausto, A and Pelini, V and Megha, T and Sardanelli, F and Mazzei, MA}, title = {Dual-Energy CT for Locoregional Staging of Breast Cancer: Preliminary Results.}, journal = {AJR. American journal of roentgenology}, volume = {214}, number = {3}, pages = {707-714}, doi = {10.2214/AJR.18.20953}, pmid = {31939699}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/*pathology ; Contrast Media ; Feasibility Studies ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Radiography, Dual-Energy Scanned Projection/*methods ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVE. The objective of this study was to demonstrate the feasibility of dual-energy CT (DECT) for locoregional staging of breast cancer and differentiation of tumor histotypes. MATERIALS AND METHODS. From January 2016 to July 2017, a total of 31 patients (mean [± SD] age, 55.8 ± 14.8 years) with breast cancer diagnosed by needle biopsy who underwent preoperative contrast-enhanced DECT for staging purposes were selected from a retrospective review of institutional databases. Monochromatic images obtained at 40 and 70 keV were evaluated by two readers who determining the number of hypervascularized tumors present and the largest tumor diameter for each breast. The attenuation values and iodine concentration of tumors and normal breast tissue and the ratios of these findings in each tissue type were recorded. Cancers were classified as ductal carcinoma in situ, invasive ductal carcinoma, and invasive lobular carcinoma. The reference standard was the final pathologic finding after surgery. RESULTS. A total of 64 tumor lesions were found at histopathologic analysis versus 67 on DECT for 34 breasts (three bilateral cancers were included). Nonparametric statistics were used. The largest lesion diameter observed DECT was 33.2 ± 20.5 mm versus 31.8 ± 20.5 mm on pathologic analysis, and cancer distribution was correctly classified for 31 of 34 (91%) cases. ROC curves derived from lesion iodine concentration showed that the optimal thresholds for distinguishing infiltrating carcinomas (invasive lobular and ductal carcinomas) and from other lesions were 1.70 mg/mL (sensitivity, 94.9%; specificity, 93.0%; AUC value, 0.968). ROC curves derived from the ratio of the iodine concentration in lesions to that in normal breast parenchyma showed that 6.13 was the optimal threshold to distinguish invasive ductal carcinoma from other lesions (sensitivity, 87.0%; specificity, 81.1%; AUC value, 0.914). CONCLUSION. DECT is feasible and seems to be a reliable tool for locoregional staging of breast cancer.}, } @article {pmid31939679, year = {2020}, author = {Zheng, J and Zhou, T and Li, F and Shi, J and Zhang, L}, title = {Clinic-Pathological Features of Breast Ductal Carcinoma in Situ with Micro-Invasion.}, journal = {Cancer investigation}, volume = {38}, number = {2}, pages = {113-121}, doi = {10.1080/07357907.2020.1715422}, pmid = {31939679}, issn = {1532-4192}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma in Situ/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/surgery ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/biosynthesis ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pathology, Clinical/*methods ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Retrospective Studies ; Young Adult ; }, abstract = {Background: To investigate the differences of clinic-pathological features among ductal carcinoma in situ (DCIS), ductal carcinoma in situ with micro-invasion (DCIS-MI) and early invasive carcinoma (IDC) in stage T1.Methods: From January 2014 to December 2018, 308 cases DCIS, DCIS-MI 92 cases and 111 cases of T1a, 343 cases of T1b, and 1032 cases of T1c were investigated in a retrospective analysis. The population and clinic-pathological characteristics including age, menstrual status, surgical mode, lymph node status and molecular markers were compared in each group. Survival rate of all patients were followed-up for 5 years.Results: Compared with DCIS-MI group, the higher breast-conserving rate and lower lymph node metastasis rate in the DCIS group were shown in the DCIS-MI group (p < .05). There were no significant differences in tumor diameter, number of tumors, ER, PR, HER2 and Ki67 expression, molecular typing, (p > .05). The expression of Ki67 in T1a, T1b and T1c groups increased gradually with elevated grades (p < .05). The proportion of HER2-positive patients in DCIS-MI group was significantly higher than that in T1a-b-c (p < .05). There were no significant differences in DFS and OS between the 3 groups (p > .05).Conclusions: The clinic-pathological features of DCIS-MI are similar to those of DCIS and T1a, but significantly different from T1c.}, } @article {pmid31937300, year = {2020}, author = {Westwood, ML and O'Donnell, AJ and Schneider, P and Albery, GF and Prior, KF and Reece, SE}, title = {Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections.}, journal = {Malaria journal}, volume = {19}, number = {1}, pages = {17}, pmid = {31937300}, issn = {1475-2875}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; UF110155//Royal Society/ ; }, mesh = {Animals ; *Circadian Rhythm/immunology ; Erythrocytes/*parasitology ; Female ; Flow Cytometry ; Gametogenesis/physiology ; Linear Models ; Malaria/blood/immunology/*parasitology ; Male ; Merozoites/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Plasmodium chabaudi/genetics/growth & development/immunology/*physiology ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tumor Necrosis Factor-alpha/*administration & dosage/blood/immunology ; }, abstract = {BACKGROUND: The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes ("conversion rate") is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host's circadian immune responses.

METHODS: First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12 h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.

RESULTS: There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.

CONCLUSIONS: The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.}, } @article {pmid31932496, year = {2020}, author = {Jelacic, TM and Ribot, WJ and Chua, J and Boyer, AE and Woolfitt, AR and Barr, JR and Friedlander, AM}, title = {Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {204}, number = {5}, pages = {1263-1273}, pmid = {31932496}, issn = {1550-6606}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Bacillus anthracis/*immunology ; Bacillus licheniformis/*immunology ; Bacillus subtilis/*immunology ; Cytokines/immunology ; Dendritic Cells/*immunology ; Female ; Humans ; *Immunity, Innate ; Macrophages/*immunology ; Male ; Monocytes/*immunology ; Polyglutamic Acid/*immunology ; }, abstract = {The poly-γ-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of d-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed d-, l-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-α, whereas B. licheniformis PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.}, } @article {pmid31931856, year = {2020}, author = {Yoosuf, N and Navarro, JF and Salmén, F and Ståhl, PL and Daub, CO}, title = {Identification and transfer of spatial transcriptomics signatures for cancer diagnosis.}, journal = {Breast cancer research : BCR}, volume = {22}, number = {1}, pages = {6}, pmid = {31931856}, issn = {1465-542X}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/*diagnosis/genetics ; Carcinoma, Ductal, Breast/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Female ; Humans ; *Machine Learning ; Molecular Typing/*methods ; ROC Curve ; Spatial Analysis ; *Transcriptome ; }, abstract = {BACKGROUND: Distinguishing ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) regions in clinical biopsies constitutes a diagnostic challenge. Spatial transcriptomics (ST) is an in situ capturing method, which allows quantification and visualization of transcriptomes in individual tissue sections. In the past, studies have shown that breast cancer samples can be used to study their transcriptomes with spatial resolution in individual tissue sections. Previously, supervised machine learning methods were used in clinical studies to predict the clinical outcomes for cancer types.

METHODS: We used four publicly available ST breast cancer datasets from breast tissue sections annotated by pathologists as non-malignant, DCIS, or IDC. We trained and tested a machine learning method (support vector machine) based on the expert annotation as well as based on automatic selection of cell types by their transcriptome profiles.

RESULTS: We identified expression signatures for expert annotated regions (non-malignant, DCIS, and IDC) and build machine learning models. Classification results for 798 expression signature transcripts showed high coincidence with the expert pathologist annotation for DCIS (100%) and IDC (96%). Extending our analysis to include all 25,179 expressed transcripts resulted in an accuracy of 99% for DCIS and 98% for IDC. Further, classification based on an automatically identified expression signature covering all ST spots of tissue sections resulted in prediction accuracy of 95% for DCIS and 91% for IDC.

CONCLUSIONS: This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.}, } @article {pmid31929965, year = {2019}, author = {Lin, L and Wang, X and Tang, C and Liang, J}, title = {Clinical Characteristics and Prognosis of Gastrointestinal Metastases in Solid Tumor Patients: A Retrospective Study and Review of Literatures.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {2019}, number = {}, pages = {4508756}, pmid = {31929965}, issn = {2210-7185}, mesh = {Adenocarcinoma/mortality/pathology/*secondary ; Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/mortality/pathology/*secondary ; Female ; Gastrointestinal Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/mortality/*pathology ; }, abstract = {BACKGROUND: According to the literature and our experience, patients with gastrointestinal metastases are relatively rare. Numerous case reports and literature reviews have been reported. We present one of the larger case series of gastrointestinal metastases.

OBJECTIVES: To explore the clinical characteristics and prognosis of patients with gastrointestinal tract metastases, which are rare metastatic sites.

METHODS: Patients with gastrointestinal metastases in the setting of stage IV primary carcinomas treated at Beijing Ditan Hospital and Peking University International Hospital from November 1992 to August 2017 were included in this study. The diagnosis of gastrointestinal tract metastases was based on histopathology.

RESULTS: 30 patients (median age 56 years, 56.7% female) were included. The most common primary carcinomas associated with gastrointestinal metastases were breast (11 patients, 36.7%), stomach (9 patients, 30.0%), and lung (4 patients, 13.3%) cancer. The major pathological types were adenocarcinoma (16 patients, 53.3%) and ductal carcinoma (9 patients, 30.0%). Ten patients (33.3%) underwent local gastrointestinal treatment, and 20 patients (66.7%) underwent nonlocal treatment (involving chemotherapy alone or best supportive care). For breast cancer patients and gastric cancer patients who underwent local therapy, a significant survival advantage was observed (p = 0.001 and p = 0.012, respectively). The presence of other common metastases was identified as an independent poor prognostic factor through multivariate analysis with a HR (hazard ratio) of survival of 0.182 (95% confidence interval (CI) 0.11-0.523, p = 0.031).

CONCLUSION: Gastrointestinal metastases are most frequently from breast invasive ductal carcinoma. The presentation of other common metastases with gastrointestinal metastasis indicates poor prognosis, and selected patients may benefit from surgical intervention.}, } @article {pmid31929443, year = {2020}, author = {Eckert, L and Mattia, L and Patel, S and Okumura, R and Reynolds, P and Stuiver, I}, title = {Reducing the Risk of Indwelling Catheter-Associated Urinary Tract Infection in Female Patients by Implementing an Alternative Female External Urinary Collection Device: A Quality Improvement Project.}, journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society}, volume = {47}, number = {1}, pages = {50-53}, doi = {10.1097/WON.0000000000000601}, pmid = {31929443}, issn = {1528-3976}, mesh = {Adult ; California ; Catheter-Related Infections/prevention & control ; Catheters, Indwelling/*adverse effects/microbiology ; Female ; Humans ; Quality Improvement ; Urinary Tract Infections/*prevention & control ; Urine Specimen Collection/methods/*standards/statistics & numerical data ; }, abstract = {PURPOSE: The purpose of this quality improvement project was to reduce catheter-associated urinary tract infection (CAUTI) risk for female patients by implementing a female external urinary collection (FEUC) device with suction as an alternative to indwelling catheter (IDC).

PARTICIPANTS AND SETTING: Participants were female patients admitted to our 386-bed community hospital in Southern California and who required urinary management.

APPROACH: We implemented a comprehensive CAUTI prevention program in 2014 that was in place for 1.5 years before this project was started. The CAUTI prevention program was based on the US Center for Disease Control and Prevention's CAUTI prevention recommendations. To supplement our CAUTI prevention efforts in our female patients, we implemented the FEUC device in our intensive care, telemetry, medical-surgical, orthopedic, and acute rehabilitations inpatient care units. Indwelling catheter use and CAUTI cases were identified by our Infection Prevention department.

OUTCOMES: Prior to introduction of the FEUC device, in 2015, the baseline female IDC utilization rate was 31.7% (7181 IDC device-days/22,656 patient-days) and the female CAUTI rate was 1.11 (8 cases/7181 IDC device-days) per 1000 days. Following introduction of the device, both rates declined. In 2016, the IDC utilization rate was 29.7% (P = .000) and the CAUTI rate was 0% (P =.005). We continued to observe a reduction in 2017 IDC utilization rates of 26% (P = .000); the 2017 CAUTI rate of 0.90 was not significantly different to our prior year rate (P = .726).

IMPLICATIONS FOR PRACTICE: We found that the introduction of the FEUC device reduced the risk for CAUTI. We will continue to prioritize the use of external devices for urinary management to help reduce the risk of our patients developing CAUTI.}, } @article {pmid31927471, year = {2020}, author = {Mema, E and Schnabel, F and Chun, J and Kaplowitz, E and Price, A and Goodgal, J and Moy, L}, title = {The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.}, journal = {European journal of radiology}, volume = {124}, number = {}, pages = {108813}, doi = {10.1016/j.ejrad.2020.108813}, pmid = {31927471}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Density/*physiology ; Cohort Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/*diagnostic imaging ; Young Adult ; }, abstract = {PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC).

METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression.

RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts.

CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.}, } @article {pmid31921678, year = {2019}, author = {Yu, LN and Liu, Z and Tian, Y and Zhao, PP and Hua, X}, title = {FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1424}, pmid = {31921678}, issn = {2234-943X}, abstract = {Biological markers that could predict the progression of ductal carcinoma in-situ (DCIS) to invasive breast cancer (IDC) are required urgently for personalized therapy for patients diagnosed with DCIS. As stroma was invaded by malignant cells, perturbed stromal-epithelial interactions would bring about tissue remodeling. With the specific expression of the fibroblast activation protein-alpha (FAP-a), Carcinoma-associated fibroblasts (CAFs) are the main cell populations in the remodeled tumor stroma. Golgi phosphoprotein 3 (GOLPH3), a documented oncogene possessing potent transforming capacity, is not only up-regulated in many tumors but also an efficient indicator of poor prognosis and more malignant tumors. The present study aimed to retrospectively evaluate the pathological value of FAP-a and GOLPH3 in predicting the recurrence or progression of DCIS to invasive breast cancer. Immunohistochemical techniques were applied to investigate the expression of FAP-a GOLPH3 in 449 cases of DCIS patients received extensive resection and with close follow-up, but not being treated with any form of chemo- or radio-therapy. The combination of FAP-a and GOLPH3 in predicating the recurrence or progression of DCIS into invasive breast cancer was specifically examined. The study demonstrated that the overexpression of FAP-a in stromal fibroblasts and GOLPH3 in carcinoma cells are highly predictive of DCIS recurrence and progression into invasive breast cancer. Both FAP-a and GOLPH3 have high specificity and sensitivity to predict the recurrence of DCIS. Moreover, the combination of FAP-a and GOLPH3 tends to further improve the specificity and sensitivity of DCIS recurrence by 9.72-10.31 and 2.72-3.63%, respectively. FAP-a and GOLPH3 serve as novel markers in predicting the recurrence or progression of DCIS into invasive breast cancer.}, } @article {pmid31912012, year = {2020}, author = {Pandit, P and Patil, R and Palwe, V and Gandhe, S and Patil, R and Nagarkar, R}, title = {Prevalence of Molecular Subtypes of Breast Cancer: A Single Institutional Experience of 2062 Patients.}, journal = {European journal of breast health}, volume = {16}, number = {1}, pages = {39-43}, pmid = {31912012}, issn = {2587-0831}, abstract = {OBJECTIVE: The aim of the study was to analyze the prevalence of molecular subtypes of all breast cancer patients treated at tertiary cancer centre in West India in 12 years.

MATERIALS AND METHODS: A retrospective observational study carried out in Tertiary Cancer Care Centre in Western India. Electronic medical records of all breast cancer patients were retrieved from the hospital database between March 2007 to March 2019. Patient's characteristic, histological features and molecular subtypes were collected and analyzed.

RESULTS: A total of 2062 women fulfilled the criteria for this study and were analyzed. The median age of study population was 51 years (range 22-100 years). Among these, 1357 (65.8%) were of ≤55 years and 705 (34.2%) were over 55 years. The overall incidence of Hormonal Receptor-positive patients (either estrogen-receptor (ER) or progesterone-receptor (PR) or both) was 1162 (56.4%). The Mean tumor size was 3.8cm (range 0-18cm). The most common histology was IDC (96%). Axillary nodes were positive in 62.5%. Luminal type A was positive in 762 (37%) patients while Luminal type B was present in 157 (7.6%) patients. Basal-like subtype was observed in 537 (26%) patients while HER2 rich subtype was seen in 229 (11.1%). The incidence of Luminal A subtype increased with age. The highest observed among patients (72%) aged 70 years or more. Incidence of Basal like subtype was highest in patients less than 30 years (52%).

CONCLUSION: Luminal-like disease is the most common molecular subtype in India. Identification of Basal like breast cancer, a highly aggressive, biologically and clinically distinct subtype different than its non-basal variant, is important for treatment planning and target therapy.}, } @article {pmid31912011, year = {2020}, author = {Hasdemir, S and Tolunay, Ş and Özşen, M and Gökgöz, MŞ}, title = {Phyllodes Tumor of the Breast: A Clinicopathological Evaluation of 55 Cases.}, journal = {European journal of breast health}, volume = {16}, number = {1}, pages = {32-38}, pmid = {31912011}, issn = {2587-0831}, abstract = {OBJECTIVE: Phyllodes tumors are biphasic tumors consisting of epithelial and stromal components that account for less than 1% of all breast tumors. According to the World Health Organization (WHO) phyllodes tumors are classified into three categories as benign, borderline and malignant. It has been reported that these tumors are usually benign and both the stromal component and the epithelial component may progress to malignancy. In this descriptive study, it was aimed to present the cases of phyllodes tumor and to evaluate the clinicopathological features of these tumors in the light of the literature.

MATERIALS AND METHODS: In our study, 55 cases of phyllodes tumor diagnosed between 2005-2018 in the Department of Medical Pathology were retrospectively studied. A total of 55 cases were included in the study.

RESULTS: All cases were female with a mean age of 39.7+15.2 years. Fifty-seven tumors diagnosed in 55 cases were classed as benign in 20 cases (35.1%), borderline in 14 cases (24.6%) and malignant phyllodes tumors in 23 cases (40.3%). Ductal carcinoma in situ (solid and cribriform type) were detected in one case with malignant phyllodes tumor, whereas invasive ductal carcinoma was detected in one case. Bilateral ductal carcinoma in situ was present in the patient with invasive ductal carcinoma.

CONCLUSION: These tumors which rapidly grow into large masses can be clinically and pathologically confused with benign lesions, macroscopic and microscopic evaluation of concomitant in situ-invasive carcinomas should be considered. Phyllodes tumors have an important role in breast surgery and pathology.}, } @article {pmid31912010, year = {2020}, author = {Duraker, N and Hot, S and Akan, A and Nayır, PÖ}, title = {A Comparison of the Clinicopathological Features, Metastasis Sites and Survival Outcomes of Invasive Lobular, Invasive Ductal and Mixed Invasive Ductal and Lobular Breast Carcinoma.}, journal = {European journal of breast health}, volume = {16}, number = {1}, pages = {22-31}, pmid = {31912010}, issn = {2587-0831}, abstract = {OBJECTIVE: We compared the breast cancer patients with invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC) and mixed invasive ductal and lobular carcinoma (IDLC) in terms of clinicopathological and treatment features, metastatic patterns and long-term survival.

MATERIALS AND METHODS: In a 10 years patient cohort, 3412 patients with unilateral breast carcinoma were enrolled in the study. Tumors were classified histologically according to criteria described by World Health Organization classification.

RESULTS: The highest rate of T3 tumors were found in IDLC patients, the lowest in IDC patients, and the difference between groups was significant only in comparison of IDC vs IDLC. Axillary positivity rate was highest in IDLC, lowest in ILC; differences were significant in comparisons of IDLC vs ILC and IDLC vs IDC. There was no significant difference between the patient groups in terms of surgical treatment, mastectomy and breast conserving surgery. Rate of bone metastasis was highest in IDLC, lowest in IDC, with significant difference between IDLC and IDC. Locoregional recurrence-free survival (LRFS) rate was 90.9% in ILC patients, 92.5% in IDC patients, 92.9% in IDLC patients, with no significant difference between the groups; in multivariate Cox analysis, histological type had no prognostic significance (p=0.599). Distant metastasis-free survival (DMFS) rate was 66.2% in ILC patients, 66.7% in IDC patients, 57.1% in IDLC patients; in multivariate Cox analysis, histological type had no prognostic significance (p=0.392).

CONCLUSION: Although these results suggest that IDLC may have a worse prognosis than IDC and ILC, in multivariate analysis LRFS and DMFS were not significantly different among the histological type groups.}, } @article {pmid31907974, year = {2020}, author = {DeVaux, RS and Ropri, AS and Grimm, SL and Hall, PA and Herrera, EO and Chittur, SV and Smith, WP and Coarfa, C and Behbod, F and Herschkowitz, JI}, title = {Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.}, journal = {Journal of cellular biochemistry}, volume = {121}, number = {7}, pages = {3465-3478}, pmid = {31907974}, issn = {1097-4644}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Interleukin-6/*genetics ; Neoplasm Invasiveness ; RNA, Antisense/*genetics ; RNA, Long Noncoding/*genetics ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.}, } @article {pmid31906804, year = {2020}, author = {Guignard, B and Rouard, A and Chollet, D and Bonifazi, M and Dalla Vedova, D and Hart, J and Seifert, L}, title = {Coordination Dynamics of Upper Limbs in Swimming: Effects of Speed and Fluid Flow Manipulation.}, journal = {Research quarterly for exercise and sport}, volume = {91}, number = {3}, pages = {433-444}, doi = {10.1080/02701367.2019.1680787}, pmid = {31906804}, issn = {2168-3824}, mesh = {Environment ; Humans ; Male ; Motor Skills/*physiology ; Swimming/*physiology ; Upper Extremity/*physiology ; Water Movements ; Young Adult ; }, abstract = {Purpose: Motor outputs are governed by dynamics organized around stable states and spontaneous transitions: we seek to investigate the swimmers' motor behavior flexibility as a function of speed and aquatic environment manipulations. Method: Eight elite male swimmers partook an eight-level incremental test (4% increment from 76% to 104% of their mean speed on 200 m front crawl) in a quasi-static aquatic environment (pool). Swimmers then partook another incremental test at similar effort in a dynamic aquatic environment (swimming flume) up to maximal speed. Stroke rate (SR), index of coordination (IdC) and intersegmental coupling of the upper limbs were computed from the inertial sensors located on the upper limbs and the sacrum. Results: With speed increase, SR values presented a steeper linear increase in the pool than in the flume. IdC values increased also in the pool but remained stable in the flume. Individual SR and IdC vs. speed increase displayed second-order polynomial dynamics, indicative of adaptive flexibility with a range of extremum values more restricted in the flume. Finally, a reduction of the in-phase coordination pattern was noted with flume speed increase. Conclusions: Action possibilities were strongly constrained in the flume at the highest speeds as the fluid flow led to discontinuity in the propulsive actions of the upper limbs and lack of in-phase inter-segmental coordination. This highlights that the behavioral flexibility was restricted in the flume in comparison to the pool, in which the exploitation of opportunities for action involved a larger number of degrees of freedom in the movement.}, } @article {pmid31902979, year = {2019}, author = {Sultan, G and Zubair, S and Tayubi, IA and Dahms, HU and Madar, IH}, title = {Towards the early detection of ductal carcinoma (a common type of breast cancer) using biomarkers linked to the PPAR(γ) signaling pathway.}, journal = {Bioinformation}, volume = {15}, number = {11}, pages = {799-805}, pmid = {31902979}, issn = {0973-2063}, abstract = {Breast cancer is a leading cause of morbidity and mortality among women comprising about 12% females worldwide. The underlying alteration in the gene expression, molecular mechanism and metabolic pathways responsible for incidence and progression of breast tumorigenesis are yet not completely understood. In the present study, potential biomarker genes involved in the early progression for early diagnosis of breast cancer has been detailed. Regulation and Gene profiling of Ductal Carcinoma In-situ (DCIS), Invasive Ductal Carcinoma (IDC) and healthy samples have been analyzed to follow their expression pattern employing normalization, statistical calculation, DEGs annotation and Protein-Protein Interaction (PPI) network. We have performed a comparative study on differentially expressed genes among Healthy vs DCIS, Healthy vsIDC and DCIS vs IDC. We found MCM102 and SLC12A8as consistently over-expressed and LEP, SORBS1, SFRP1, PLIN1, FABP4, RBP4, CD300LG, ID4, CRYAB, ECRG4, G0S2, FMO2, ADAMTS5, CAV1, CAV2, ABCA8, MAMDC2, IGFBP6, CLDN11, TGFBR3as under-expressed genes in all the 3 conditions categorized for pre-invasive and invasive ductal breast carcinoma. These genes were further studied for the active pathways where PPAR(γ) signaling pathway was found to be significantly involved. The gene expression profile database can be a potential tool in the early diagnosis of breast cancer.}, } @article {pmid31902119, year = {2020}, author = {Acun, T and Senses, KM}, title = {Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {27}, number = {3}, pages = {483-489}, pmid = {31902119}, issn = {1880-4233}, support = {2017-50737594-02//Bülent Ecevit Üniversitesi/ ; 217S251//Türkiye Bilimsel ve Teknolojik Araştirma Kurumu/ ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*mortality/pathology ; DNA Copy Number Variations ; *DNA Methylation ; Down-Regulation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; Humans ; *Mutation ; Prognosis ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; Survival Rate ; }, abstract = {BACKGROUND: DNAJC10 (ERDJ5), a member of HSP40 family, was considered as an anti-oncogenic gene in neuroblastoma, prostate and colon cancers. But, the role and importance of DNAJC10 gene in breast cancer is currently unknown. In this study, in vitro/in vivo expression, biomarker potential and genetic/epigenetic alterations of DNAJC10 were analyzed in breast cancer.

METHODS: Real-time qRT-PCR and immunohistochemistry methods were used to determine the expression level of DNAJC10 gene in breast cancer cell lines and clinical samples. The Kaplan-Meier plotter was used to evaluate the survival prognostic value of DNAJC10 mRNA expression in breast cancer patients. Mutation screening software and methylation-specific PCR were used to screen genetic alterations and methylation status of DNAJC10 promoter regions, respectively.

RESULTS: DNAJC10 mRNA expression was significantly reduced in 3 out of 4 breast cancer cell lines compared to the nontumorigenic mammary epithelial cell line (MCF 10A). DNAJC10 protein expression was significantly less frequent in invasive ductal carcinoma samples (n = 121) compared with adjacent normal breast tissues (n = 32) (p < 0.0001). Downregulation of DNAJC10 mRNA was associated with poor overall survival (OS) (n = 626) (p = 0.0096) and relapse-free survival (n = 1764) (p = 5.3e-12). According to the COSMIC and cBioPortal databases, point mutations and copy number variations of DNAJC10 were very rare in breast cancer samples. Besides, no genetic alterations on the experimentally validated promoter regions were found in breast cell lines. CpG island located in the promoter regions of DNAJC10 gene was found to be frequently hypomethylated in breast cell lines.

CONCLUSIONS: In the light of previous knowledge regarding the role of DNAJC10 in carcinogenesis, findings of this study suggest that DNAJC10 is a potential diagnostic/prognostic biomarker and tumor suppressor candidate for breast cancer. Epigenetic factors other than promoter methylation could contribute to the downregulation of DNAJC10 expression.}, } @article {pmid31897358, year = {2019}, author = {Alzahrani, W and Althoubaity, F and Alsobhi, D and Mohamed, Y and AlMutairi, A and Sindi, D and Alharbi, R and Zaidi, N}, title = {Clinicopathological Features and Metastatic Pattern of Triple-positive Breast Cancer Among Female Patients at a Tertiary Care Hospital.}, journal = {Cureus}, volume = {11}, number = {12}, pages = {e6458}, pmid = {31897358}, issn = {2168-8184}, abstract = {Objectives The heterogenicity of breast cancer (BC) is determined by the status of human epidermal growth factor receptor 2 (HER2/neu), estrogen receptor (ER), and progesterone receptor (PR). Triple-positive BC (TPBC) expresses the amplification/overexpression of the HER2 pathway and is positive for ER and PR. This subtype has a distinct clinical behavior. However, very few studies are focused on TPBC. This study investigated the clinicopathological features and metastatic pattern of TPBC. Methods A seven-year retrospective study was conducted at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia. All females with TPBC diagnosed between January 1, 2010, and June 30, 2017, were enrolled. Mean and standard deviation were calculated. Results From 1205 BC patients, the TPBC incidence was 10% (n = 124). The mean age at diagnosis was 51 years. On physical examination, a high tendency to show pathological skin changes was observed. Invasive ductal carcinoma was the most common histological type, presenting with a poorly differentiated histological grade (grade 3). Over a median two-year follow-up, the incidence of metastasis was 27.4% (n = 34). Bone was the most common site. The incidence of locoregional recurrence was 9.7%. Overall survival was 89.5%. Conclusion TPBC has an early tendency for metastasis and commonly affects the breast skin. BC should be approached based on the immunohistochemical diagnosis. We encourage more comprehensive studies to target TPBC for more insights into the heterogeneity of BC.}, } @article {pmid31897333, year = {2019}, author = {Kim, HS and Lee, JU and Yoo, TK and Chae, BJ and Son, D and Kim, YJ and Park, WC}, title = {Omission of Chemotherapy for the Treatment of Mucinous Breast Cancer: A Nationwide Study from the Korean Breast Cancer Society.}, journal = {Journal of breast cancer}, volume = {22}, number = {4}, pages = {599-612}, pmid = {31897333}, issn = {1738-6756}, abstract = {PURPOSE: Mucinous breast carcinoma (MBC) is a rare type of breast cancer. Although patients with MBC may have a better prognosis than that of patients with invasive ductal carcinoma, many clinicians administer adjuvant chemotherapy regimens similar to those for other breast tumors. Using data from a nationwide clinical database, this study evaluated the significance of adjuvant systemic chemotherapy and whether it can be omitted in MBC patients.

METHODS: We included 3,076 patients with a diagnosis of MBC recorded in the Korean Breast Cancer Registry between January 1990 and August 2016. We used the Kaplan-Meier method to analyze breast cancer-specific survival (BCCS) and overall survival (OS). Multivariate analysis was performed using a Cox proportional hazard ratio (HR) model to estimate the adjusted HR for each prognostic factor.

RESULTS: A total of 2,988 MBC patients were enrolled and followed-up for a median of 100 months (range, 2-324 months). Multivariate analysis revealed that axillary lymph node (ALN) metastasis and estrogen receptor (ER) negativity were significant prognostic factors for BCSS. Meanwhile, old age, pathologic tumor stage, and ALN metastasis were significant prognostic factors for OS. Subgroup analysis of ER-positive MBC showed that ALN metastasis was a significant prognostic factor for BCSS. Additionally, old age, pathologic tumor stage, and ALN metastasis were prognostic factors for OS. Ultimately, ALN metastasis was the most statistically significant prognostic factor for MBC. However, chemotherapy had no significant effect on BCSS and OS. The Kaplan-Meier curves of BCSS and OS based on pathologic tumor and nodal stages and age revealed that chemotherapy did not statistically significantly improve prognosis, except for the N3 stage.

CONCLUSION: Our large retrospective analysis revealed that adjuvant chemotherapy provided little benefit to improve the prognosis of most ER-positive MBC patients. Therefore, chemotherapy can be omitted in the treatment of most ER-positive MBC.}, } @article {pmid31894281, year = {2020}, author = {Zhao, C and Zheng, S and Yan, Z and Deng, Z and Wang, R and Zhang, B}, title = {CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.}, journal = {Oncology reports}, volume = {43}, number = {2}, pages = {571-580}, doi = {10.3892/or.2019.7426}, pmid = {31894281}, issn = {1791-2431}, mesh = {Adult ; Aged ; Animals ; Annexin A2/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Chemokines, CC/*metabolism ; Disease Progression ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism/*pathology/*secondary ; MCF-7 Cells ; Mice ; Middle Aged ; Neoplasm Transplantation ; Tumor Burden ; }, abstract = {Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F‑actin measurement assay showed that reduction of AnxA2 suppressed CCL18‑induced F‑actin polymerization though phosphorylation of integrin β1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18‑induced EMT via the PI3K/Akt/GSK3β/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti‑invasion/metastasis target for therapeutic intervention in breast cancer.}, } @article {pmid31889895, year = {2019}, author = {Wang, L and Xu, C and Liu, X and Yang, Y and Cao, L and Xiang, G and Liu, F and Wang, S and Liu, J and Meng, Q and Jiao, J and Niu, Y}, title = {TGF-β1 stimulates epithelial-mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer.}, journal = {Cancer cell international}, volume = {19}, number = {}, pages = {343}, pmid = {31889895}, issn = {1475-2867}, abstract = {BACKGROUND: The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer.

METHODS: EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell-cell interactions in the development of invasive breast cancer.

RESULTS: We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo.

CONCLUSIONS: In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.}, } @article {pmid31883686, year = {2020}, author = {Zhang, J and Feng, T and Yan, F and Qiao, S and Wang, X}, title = {Analysis and design on intervehicle distance control of autonomous vehicle platoons.}, journal = {ISA transactions}, volume = {100}, number = {}, pages = {446-453}, doi = {10.1016/j.isatra.2019.12.007}, pmid = {31883686}, issn = {1879-2022}, abstract = {This paper presents an intervehicle distance control (IDC) to solve the problem of autonomous vehicle platooning, motivated by future automated highway system (AHS) or smart road which is proposed as intelligent transportation system (ITS) technology. First the velocity and position control of the single vehicle is studied based on internal model compensator. And then the platooning problem on multiple vehicles is solved in the light of multiagent concept. Moreover, the platoon condition is derived for the corresponding scheme. Further we analyze the influence of controller parameters on the whole system, and propose the guidance for parameter design. Finally some simulations are used to verify the effectiveness of the proposed IDC scheme with an analysis on controller parameters.}, } @article {pmid31876826, year = {2020}, author = {Phan Sy, O and Rouchy, RC and De Leiris, N and Nika, E and Djaileb, L}, title = {FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e169-e170}, doi = {10.1097/RLU.0000000000002894}, pmid = {31876826}, issn = {1536-0229}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/complications/*surgery ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Granuloma/*diagnostic imaging/*etiology/pathology ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Silicones/*adverse effects ; }, abstract = {We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical "snowstorm" appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.}, } @article {pmid31876580, year = {2020}, author = {Gandhi, JS and Smith, SC and Paner, GP and McKenney, JK and Sekhri, R and Osunkoya, AO and Baras, AS and DeMarzo, AM and Cheville, JC and Jimenez, RE and Trpkov, K and Colecchia, M and Ro, JY and Montironi, R and Menon, S and Hes, O and Williamson, SR and Hirsch, MS and Netto, GJ and Fine, SW and Sirohi, D and Kaushal, S and Sangoi, A and Robinson, BD and Kweldam, CF and Humphrey, PA and Hansel, DE and Schultz, L and Magi-Galluzzi, C and Przybycin, CG and Shah, RB and Mehra, R and Kunju, LP and Aron, M and Kryvenko, ON and Kench, JG and Kuroda, N and Tavora, F and van der Kwast, T and Grignon, DJ and Epstein, JI and Reuter, VE and Amin, MB}, title = {Reporting Practices and Resource Utilization in the Era of Intraductal Carcinoma of the Prostate: A Survey of Genitourinary Subspecialists.}, journal = {The American journal of surgical pathology}, volume = {44}, number = {5}, pages = {673-680}, doi = {10.1097/PAS.0000000000001417}, pmid = {31876580}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle/trends ; Carcinoma, Ductal/chemistry/*pathology/therapy ; Health Care Surveys ; Health Resources/*trends ; Humans ; Immunohistochemistry/*trends ; Male ; Neoplasm Grading ; Practice Patterns, Physicians'/*trends ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/*pathology/therapy ; Reproducibility of Results ; Specialization/*trends ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.}, } @article {pmid31876012, year = {2020}, author = {Holtmaat, K and van der Spek, N and Lissenberg-Witte, B and Breitbart, W and Cuijpers, P and Verdonck-de Leeuw, I}, title = {Long-term efficacy of meaning-centered group psychotherapy for cancer survivors: 2-Year follow-up results of a randomized controlled trial.}, journal = {Psycho-oncology}, volume = {29}, number = {4}, pages = {711-718}, pmid = {31876012}, issn = {1099-1611}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Cancer Survivors/*psychology ; Depression/*therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Netherlands ; *Outcome Assessment, Health Care ; Psychotherapy, Group/*methods ; Quality of Life/psychology ; }, abstract = {OBJECTIVE: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention to improve personal meaning, psychological well-being, and depressive symptoms until 6 months after the intervention. In this study, the long-term effects of MCGP-CS (i.e., at 1- and 2-year follow-up) on meaning, psychological well-being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU).

METHODS: Cancer survivors (n = 170) were randomized into MCGP-CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well-Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention-to-treat (ITT) basis, as well as for intervention completers only.

RESULTS: LMM and post hoc analyses with Bonferroni correction revealed that MCGP-CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2-year postintervention (ITT analysis, Cohen's d = .82). Completers also reported more personal growth (subscale of SPWB) after MCGP-CS than after SGP 1-year postintervention (Cohen's d = .94). No long-term effects were found on the other outcome measures.

CONCLUSIONS: In the 2 years after MCGP-CS, the short-term significant effects on personal meaning and most positive effects related to psychological well-being faded. However, MCGP-CS had a long-term positive effect on positive relations with others and on survivors' sense of personal growth.

TRIAL REGISTRATION: Netherlands Trial Register: NTR3571.}, } @article {pmid31873214, year = {2020}, author = {Pleitez, MA and Khan, AA and Soldà, A and Chmyrov, A and Reber, J and Gasparin, F and Seeger, MR and Schätz, B and Herzig, S and Scheideler, M and Ntziachristos, V}, title = {Label-free metabolic imaging by mid-infrared optoacoustic microscopy in living cells.}, journal = {Nature biotechnology}, volume = {38}, number = {3}, pages = {293-296}, pmid = {31873214}, issn = {1546-1696}, mesh = {3T3-L1 Cells ; Adipogenesis ; Animals ; Carbohydrate Metabolism ; HeLa Cells ; Humans ; Image Enhancement/*methods ; Lipid Droplets/*metabolism ; Mice ; Microscopy ; Photoacoustic Techniques/*methods ; Software ; Spectroscopy, Fourier Transform Infrared ; }, abstract = {We develop mid-infrared optoacoustic microscopy (MiROM) for label-free, bond-selective, live-cell metabolic imaging, enabling spatiotemporal monitoring of carbohydrates, lipids and proteins in cells and tissues. Using acoustic detection of optical absorption, MiROM converts mid-infrared sensing into a positive-contrast imaging modality with negligible photodamage and high sensitivity. We use MiROM to observe changes in intrinsic carbohydrate distribution from a diffusive spatial pattern to tight co-localization with lipid droplets during adipogenesis.}, } @article {pmid31871301, year = {2020}, author = {Chen, G and Ding, XF and Pressley, K and Bouamar, H and Wang, B and Zheng, G and Broome, LE and Nazarullah, A and Brenner, AJ and Kaklamani, V and Jatoi, I and Sun, LZ}, title = {Everolimus Inhibits the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer Via Downregulation of MMP9 Expression.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1486-1496}, pmid = {31871301}, issn = {1557-3265}, support = {P30 CA054174/CA/NCI NIH HHS/United States ; R01 CA192564/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Down-Regulation ; Everolimus/*pharmacology ; Female ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Nude ; Mice, Transgenic ; Receptor, ErbB-2/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: We evaluated the role of everolimus in the prevention of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) progression.

EXPERIMENTAL DESIGN: The effects of everolimus on breast cancer cell invasion, DCIS formation, and DCIS progression to IDC were investigated in a 3D cell culturing model, intraductal DCIS xenograft model, and spontaneous MMTV-Her2/neu mouse model. The effect of everolimus on matrix metalloproteinase 9 (MMP9) expression was determined with Western blotting and IHC in these models and in patients with DCIS before and after a window trial with rapamycin. Whether MMP9 mediates the inhibition of DCIS progression to IDC by everolimus was investigated with knockdown or overexpression of MMP9 in breast cancer cells.

RESULTS: Everolimus significantly inhibited the invasion of human breast cancer cells in vitro. Daily intragastric treatment with everolimus for 7 days significantly reduced the number of invasive lesions from intraductal DCIS foci and inhibited DCIS progression to IDC in the MMTV-Her2/neu mouse mammary tumor model. Mechanistically, everolimus treatment decreased the expression of MMP9 in the in vitro and in vivo models, and in breast tissues from patients with DCIS treated with rapamycin for 1 week. Moreover, overexpression of MMP9 stimulated the invasion, whereas knockdown of MMP9 inhibited the invasion of breast cancer cell-formed spheroids in vitro and DCIS in vivo. Knockdown of MMP9 also nullified the invasion inhibition by everolimus in vitro and in vivo.

CONCLUSIONS: Targeting mTORC1 can inhibit DCIS progression to IDC via MMP9 and may be a potential strategy for DCIS or early-stage IDC therapy.}, } @article {pmid31867075, year = {2019}, author = {Choi, BW and Jeong, YJ and Park, SH and Oh, HK and Kang, S}, title = {Reverse Warburg Effect-Related Mitochondrial Activity and [18]F-FDG Uptake in Invasive Ductal Carcinoma.}, journal = {Nuclear medicine and molecular imaging}, volume = {53}, number = {6}, pages = {396-405}, pmid = {31867075}, issn = {1869-3474}, abstract = {PURPOSE: We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose ([18]F-FDG) uptake and mitochondrial activity in cancer cells and investigated the prognostic implications of this relationship in patients with invasive ductal carcinoma of the breast (IDCB).

METHODS: One hundred forty-six patients with primary IDCB who underwent preoperative [18]F-FDG PET/CT followed by curative surgical resection were enrolled in the current study. Mitochondrial activity of cancer cells was assessed based on translocase of outer mitochondrial membrane 20 (TOMM20) expression and cytochrome C oxidase (COX) activity. A Pearson's correlation analysis was used to assess the relationship between the maximum standardized uptake value of the primary tumour (pSUVmax) and mitochondrial activity. Clinicopathological factors, including pSUVmax, histological grade, oestrogen receptor (ER), progesterone receptor (PR), and TOMM20 expression; and COX activity, were assessed for the prediction of disease-free survival (DFS) using the Kaplan-Meier method and Cox proportional hazards model.

RESULTS: Fourteen of the 146 subjects (9.6%) showed tumour recurrence. There was a significant positive correlation between [18]F-FDG uptake and the mitochondrial activity of cancer cells in patients with IDCB, and increased [18]F-FDG uptake and mitochondrial activity were significantly associated with a shorter DFS. Additionally, results from the receiver-operating curve analysis demonstrated that the cut-off values of pSUVmax, TOMM20 expression, and COX activity for the prediction of DFS were 7.76, 4, and 5, respectively. Further, results from the univariate analysis revealed that pSUVmax, TOMM20 expression, PR status, and histologic grade were significantly associated with DFS; however, the multivariate analysis revealed that only pSUVmax was associated with DFS (HR, 6.51; 95% CI, 1.91, 22.20; P = 0.003).

CONCLUSIONS: The assessment of preoperative [18]F-FDG uptake and post-surgical mitochondrial activity may be used for the prediction of DFS in patients with IDCB.}, } @article {pmid31866423, year = {2020}, author = {Liberman, U and Ram, Y and Altenberg, L and Feldman, MW}, title = {The evolution of frequency-dependent cultural transmission.}, journal = {Theoretical population biology}, volume = {132}, number = {}, pages = {69-81}, doi = {10.1016/j.tpb.2019.12.004}, pmid = {31866423}, issn = {1096-0325}, mesh = {Biological Evolution ; *Cultural Evolution ; Phenotype ; Polymorphism, Genetic ; *Selection, Genetic ; }, abstract = {In a model of vertical and oblique cultural transmission of a dichotomous trait, the rates of transmission of each form of the trait are functions of the trait frequency in the population. Sufficient conditions on these functions are derived for a stable trait polymorphism to exist. If the vertical transmission rates are monotone decreasing functions of the trait frequency, a complete global stability analysis is presented. It is also shown that a unique protected polymorphism can be globally stable even though the sufficient conditions are not met. The evolution of frequency-dependent transmission is modeled using modifier theory, and exact conditions are derived for a transmission modifier to invade a population at a stable polymorphism. Finally, the interaction between frequency-dependent selection and frequency-dependent transmission is explored.}, } @article {pmid31864391, year = {2019}, author = {Kinj, R and Chand, ME and Gal, J and Gautier, M and Lam Cham Kee, D and Hannoun-Lévi, JM}, title = {Five-year oncological outcome after a single fraction of accelerated partial breast irradiation in the elderly.}, journal = {Radiation oncology (London, England)}, volume = {14}, number = {1}, pages = {234}, pmid = {31864391}, issn = {1748-717X}, mesh = {Aged ; Aged, 80 and over ; Brachytherapy/*mortality ; Breast Neoplasms/*mortality/pathology/radiotherapy ; Carcinoma, Ductal, Breast/*mortality/pathology/radiotherapy ; Carcinoma, Lobular/*mortality/pathology/radiotherapy ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Dose Fractionation, Radiation ; Female ; Humans ; Neoplasm Recurrence, Local/*mortality/pathology/radiotherapy ; Prognosis ; Retrospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: To update the clinical outcome of an elderly women cohort with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB).

MATERIAL AND METHODS: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB APBI. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 5 years was reported based on local relapse free survival (LRFS), specific survival (SS) and overall survival (OS). Late toxicity was evaluated. Cosmetic results were evaluated clinically by the physician.

RESULTS: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 64 months (range: 56-71), no local relapse occurred while 1 pt. developed an axillary relapse (2.1%). No Grade 3 or higher late toxicity was observed while 16 late toxicities occurred (G1: 14 events [87.5%) mainly G1 breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.

CONCLUSION: We confirmed the safety of the process and remained encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a very APBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report.}, } @article {pmid31861274, year = {2019}, author = {Micus, S and Kirsten, I and Haupt, M and Gresser, GT}, title = {Analysis of Hot Bar Soldering, Insulation Displacement Connections (IDC), and Anisotropic Conductive Adhesives (ACA), for the Automated Production of Smart Textiles.}, journal = {Sensors (Basel, Switzerland)}, volume = {20}, number = {1}, pages = {}, pmid = {31861274}, issn = {1424-8220}, abstract = {Despite all the growth forecasts of the smart textiles market, there is no stable automated manufacturing process for attaching classic electronics to textiles. The great amount of manual production steps causes high prices, which slow down market growth. During the production process, the contacting step offers the greatest potential to reduce manual manufacturing steps. For this reason, we have analyzed various contacting methods for electronic parts on conductive yarns that have a high potential for automation. The chosen methods were thermode soldering, insulation-displacement connectors and anisotropic conductive adhesives. In order to ensure reliable mechanical contacting, the samples were tested in a peeling experiment. The examination of the contact resistances took place in the context of a resistance test using four-wire measuring technology.}, } @article {pmid31860754, year = {2020}, author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Ishida, R and Kamihira, O and Sano, T and Majima, T and Ishida, S and Funahashi, Y and Sassa, N and Fujita, T and Matsukawa, Y and Hattori, R and Gotoh, M and Tsuzuki, T}, title = {Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.}, journal = {The Prostate}, volume = {80}, number = {3}, pages = {284-290}, doi = {10.1002/pros.23942}, pmid = {31860754}, issn = {1097-0045}, mesh = {Aged ; Aged, 80 and over ; Androgen Antagonists/*administration & dosage ; Carcinoma, Intraductal, Noninfiltrating/blood/*drug therapy/pathology/*surgery ; Disease-Free Survival ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/blood/*drug therapy/pathology/*surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance.

METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens.

RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively).

CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.}, } @article {pmid31859887, year = {2019}, author = {Kustic, D and Lovasic, F and Belac-Lovasic, I and Avirovic, M and Ruzic, A and Petretic-Majnaric, S}, title = {Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma.}, journal = {Revista medica de Chile}, volume = {147}, number = {5}, pages = {557-567}, doi = {10.4067/S0034-98872019000500557}, pmid = {31859887}, issn = {0717-6163}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2/*analysis ; Retrospective Studies ; Sentinel Lymph Node/*pathology ; Statistics, Nonparametric ; Time Factors ; Tumor Burden ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common malignancy in women.

AIM: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period.

PATIENTS AND METHODS: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy.

RESULTS: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival.

CONCLUSIONS: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.}, } @article {pmid31858451, year = {2020}, author = {Ryan, PC and Ryan, ÉJ and Keenan, RA and Haroon, UM and Broe, MP and Forde, JC and Galvin, D and Lennon, GM and Murphy, M and Quinlan, DM and Mulvin, DW}, title = {Admission of patients with acute urinary retention leads to a definitive management decision.}, journal = {Irish journal of medical science}, volume = {189}, number = {3}, pages = {999-1003}, doi = {10.1007/s11845-019-02164-8}, pmid = {31858451}, issn = {1863-4362}, mesh = {Acute Disease ; Aged ; Aged, 80 and over ; Hospitalization/*trends ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; Urinary Retention/*therapy ; }, abstract = {BACKGROUND: Acute urinary retention (AUR) is a common urologic emergency. However, its management is not standardized due to lack of clinical guidelines.

AIMS: We retrospectively reviewed the treatment of all male patients admitted to our institution with AUR over 12 months.

METHODS: Data was obtained from the HIPE (Hospital Inpatient Enquiry) data system, each patient's electronic discharge summary and from patient medical records.

RESULTS: There were 130 AUR admissions during the period. About 74 admissions were due to benign prostatic enlargement (BPE). Of these, 45.9% (n = 34) passed their trial without catheter (TWOC). The remainder (n = 40) failed their TWOC necessitating recatheterization and consideration for transurethral resection of prostate (TURP) or re-TWOC. An indwelling urinary catheter (IDC) was inserted for 27.5% (n = 11) of patients with a failed TWOC secondary to comorbidities. This group had a mean age of 78 years (range 68-96 years). Of those who failed their TWOC, 32.5% (n = 13) had a TURP on index admission. Of the remaining 16 patients with failed TWOC, 75% (n = 12) were discharged with an IDC and readmitted for an elective TURP with a median waiting time of 55 days (range 17-138 days). 18.75% (n = 3) passed a re-TWOC and thus offset the need to have any surgical intervention and 6.25% (n = 1) proceeded to a radical retropubic prostatectomy for biopsy proven prostate adenocarcinoma.

CONCLUSION: Admission of patients with acute urinary retention leads to a definitive management decision and reduced prolonged catheterization.}, } @article {pmid31856858, year = {2019}, author = {Wan, L and Liu, T and Hong, Z and Pan, Y and Sizemore, ST and Zhang, J and Ma, Z}, title = {NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {148}, pmid = {31856858}, issn = {1465-542X}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Receptor, IGF Type 1/metabolism ; Young Adult ; }, abstract = {BACKGROUND: A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.

METHODS: The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.

RESULTS: NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively).

CONCLUSIONS: NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.}, } @article {pmid31856344, year = {2020}, author = {Giles, M and Graham, L and Ball, J and King, J and Watts, W and Harris, A and Oldmeadow, C and Ling, R and Paul, M and O'Brien, A and Parker, V and Wiggers, J and Foureur, M}, title = {Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.}, journal = {Journal of clinical nursing}, volume = {29}, number = {5-6}, pages = {872-886}, doi = {10.1111/jocn.15142}, pmid = {31856344}, issn = {1365-2702}, support = {//NSW Ministry of Health Translational Research Grants Scheme/ ; }, mesh = {Adult ; Catheter-Related Infections/etiology/*prevention & control ; Catheters, Indwelling/*adverse effects ; Controlled Before-After Studies ; Female ; Humans ; Male ; New South Wales ; Patient Care Bundles/*nursing ; Practice Patterns, Nurses' ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/etiology/*prevention & control ; }, abstract = {AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention.

BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate.

DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach.

METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9 months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1).

RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9 months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4 months (between -2% and 4%) and 9 months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided.

CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9 months postintervention.

Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.}, } @article {pmid31856180, year = {2019}, author = {Walzer, KA and Fradin, H and Emerson, LY and Corcoran, DL and Chi, JT}, title = {Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.}, journal = {PLoS genetics}, volume = {15}, number = {12}, pages = {e1008506}, pmid = {31856180}, issn = {1553-7404}, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization, Fluorescence/*methods ; Life Cycle Stages ; Microfluidic Analytical Techniques ; Multigene Family ; Plasmodium falciparum/genetics/*growth & development ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; }, abstract = {Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the intraerythrocytic developmental cycle (IDC). During the IDC, P. falciparum progresses through a synchronous and continuous cascade of transcriptional programming previously established using population analyses. While individual parasites are known to exhibit transcriptional variations to evade the host immune system or commit to a sexual fate, such rare expression heterogeneity is largely undetectable on a population level. Therefore, we combined single-cell RNA-sequencing (scRNA-seq) on a microfluidic platform and fluorescence imaging to delineate the transcriptional variations among individual parasites during late asexual and sexual stages. The comparison between asexual and sexual parasites uncovered a set of previously undefined sex-specific genes. Asexual parasites were segregated into three distinct clusters based on the differential expression of genes encoding SERAs, rhoptry proteins, and EXP2 plus transporters. Multiple pseudotime analyses revealed that these stage-specific transitions are distinct. RNA fluorescent in situ hybridization of cluster-specific genes validated distinct stage-specific expression and transitions during the IDC and defined the highly variable transcriptional pattern of EXP2. Additionally, these analyses indicated huge variations in the stage-specific transcript levels among parasites. Overall, scRNA-seq and RNA-FISH of P. falciparum revealed distinct stage transitions and unexpected degrees of heterogeneity with potential impact on transcriptional regulation during the IDC and adaptive responses to the host.}, } @article {pmid31849934, year = {2019}, author = {Alexia, C and Cren, M and Louis-Plence, P and Vo, DN and El Ahmadi, Y and Dufourcq-Lopez, E and Lu, ZY and Hernandez, J and Shamilov, F and Chernysheva, O and Vasilieva, M and Vorotnikov, I and Vishnevskay, Y and Tupitsyn, N and Rossi, JF and Villalba, M}, title = {Polyoxidonium[®] Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2693}, pmid = {31849934}, issn = {1664-3224}, mesh = {Adenocarcinoma/*drug therapy/immunology ; Adjuvants, Immunologic/*therapeutic use ; Adult ; Aged ; Breast Neoplasms/*drug therapy/immunology ; Cell Differentiation/drug effects/immunology ; Chemotherapy, Adjuvant/methods ; Dendritic Cells/*drug effects/immunology ; Female ; Humans ; Killer Cells, Natural/drug effects/immunology ; Lymphocyte Activation/drug effects/immunology ; Lymphocytes, Tumor-Infiltrating/drug effects/immunology ; Middle Aged ; Neoadjuvant Therapy/methods ; Piperazines/*therapeutic use ; Polymers/*therapeutic use ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; }, abstract = {Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4[+] T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimulatory molecules, inducing the proliferation of allogeneic T cells. In contrast, PO decreases DC viability when added at day 5 post-expansion. PO is not toxic for NK cells at doses up to 100 μM and does not affect their activation, maturation, and cytotoxicity but tends to increase degranulation. This could be beneficial against target cells that show low sensitivity to NK cells, e.g., solid tumor cells. Finally, we have found great variability in PO response between donors. In summary, our in vitro results show that PO increases the number of costimulatory molecules on DC that prime T cells, favoring the production of effector T cells. This may support the future clinical development of PO in cancer treatment.}, } @article {pmid31849088, year = {2020}, author = {Arispe Angulo, KR and Jawa, Z and Visotcky, A and Majidi, SS and Chitambar, CR and Jorns, JM}, title = {A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.}, journal = {Histopathology}, volume = {76}, number = {5}, pages = {661-670}, doi = {10.1111/his.14049}, pmid = {31849088}, issn = {1365-2559}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoadjuvant Therapy/methods ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.

METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.

CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.}, } @article {pmid31844635, year = {2019}, author = {Redell, M and Sierra-Hoffman, M and Assi, M and Bochan, M and Chansolme, D and Gandhi, A and Sheridan, K and Soosaipillai, I and Walsh, T and Massey, J}, title = {The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.}, journal = {Open forum infectious diseases}, volume = {6}, number = {11}, pages = {ofz479}, pmid = {31844635}, issn = {2328-8957}, abstract = {BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens.

METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections.

RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%.

CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.}, } @article {pmid31844366, year = {2019}, author = {Ramesh, P and Srikumar, S and Mahendran, V and Nair, SS and Radhamany, K}, title = {Pregnancy-Associated Breast Cancer: A Realistic Approach.}, journal = {Journal of obstetrics and gynaecology of India}, volume = {69}, number = {6}, pages = {514-519}, pmid = {31844366}, issn = {0971-9202}, abstract = {BACKGROUND: The number of cancers diagnosed during pregnancy is on the rise, and breast cancer is the most common malignancy. Presently, there are very limited resources and no clear guidelines for managing this peculiar patient population both worldwide and in India. The objective of this study was to find out the incidence of pregnancy-associated breast cancer (PABC) in a tertiary care referral centre and to compare the epidemiological, diagnostic and prognostic factors as well as maternal and foetal outcomes with the most recent literature worldwide.

METHODS: We conducted a retrospective descriptive study of women diagnosed with breast cancer in pregnancy and post-partum period at a tertiary care centre in southern India during the period of 10 years (total number of breast cancer patients were 10). We studied the diagnostic and prognostic factors as well as maternal and foetal outcome in patients diagnosed with breast cancer for the first time in pregnancy.

RESULTS: Overall incidence of PABC was found to be 0.6% (n = 10). Mean age at the time of presentation was 30.7 ± 4 years. All cases suspected clinically or on imaging (USG) were confirmed with FNAC, excision biopsy or Trucut biopsy. Out of 10 patients, 70% (n = 7) had an advanced-stage disease on diagnosis. Histopathology suggested 90% (n = 9) had invasive ductal carcinoma and 55.5% (n = 5) had a triple negative receptor status. 20% (n = 2) of our patients had opted for a breast conservation surgery (BCS), and 70% (n = 7) of our patients underwent modified radical mastectomy with neoadjuvant or adjuvant chemotherapy/radiotherapy. One patient had a second trimester MTP in view of stage 4 disease. 77.7% (n = 7) of the nine patients who continued pregnancy underwent LSCS, out of which 57.4% (n = 4) were elective, and MRM was done concurrently with LSCS in 50% (n = 2) of the elective LSCS. The mean birth weight of the 9 neonates was 2.2 ± 0.5 kg. Intrauterine growth retardation was seen in 22.2% (n = 2) neonates. 33.3% (n = 3) of the neonates required NICU support, and one baby expired on post-natal day 16.

CONCLUSION: With the increasing number of elderly primigravida amongst the urban population, a clear understanding of PABC is becoming more important. A multidisciplinary team approach shall help the clinician not only in reducing the heavy burden of patient responsibility but more importantly, in guaranteeing better quality of treatment, avoiding unnecessary delays in providing interventions and providing adequate treatment.}, } @article {pmid31844357, year = {2019}, author = {Amadi, OF and Okeke, IB and Ndu, IK and Ekwochi, U and Nduagubam, OC and Ezenwosu, OU and Asinobi, IN and Osuorah, CD}, title = {Cancer Mortality in the Niger Delta Region of Nigeria: A Case Study of the University of Port Harcourt Teaching Hospital.}, journal = {Nigerian medical journal : journal of the Nigeria Medical Association}, volume = {60}, number = {5}, pages = {262-267}, pmid = {31844357}, issn = {0300-1652}, abstract = {AIM: The aim of this study is to determine the pattern of cancer mortality (CM) seen in the University of Port Harcourt Teaching Hospital (UPTH) which is a cancer reference center in the Niger Delta Region.

METHODOLOGY: This is a 6-year retrospective study of cancer-related deaths in UPTH using patients' admission registers in all the wards and emergency units. Furthermore, the death certificates of cases were reviewed.

RESULTS: Three hundred and sixteen cases of cancer-related deaths occurred, involving 174 females and 142 males, in a female-to-male sex ratio of 1.2:1. All age groups were affected, with age group 40-49 years accounting for the majority (20.6%). CM was seen in all the systems, except the central nervous system. Cancers of the gastrointestinal tract and its accessory organs (liver and gall bladder) caused most mortality (27.9%), in a female-to-male ratio of 0.8:1. The single most involved organ in CM is the female breast (20.6%), distantly followed by mortality due to prostate cancers and hematolymphoid cancers which accounted for 9.2% each. Colorectal cancers accounted for 7.3% of cancer deaths and ranked 4[th]. Cancers of both cervix and stomach each accounted for 5.7% of mortality. The major histologic diagnoses were carcinomas (adenocarcinoma; 36.7%, invasive ductal carcinoma; 20.3%, squamous cell carcinomas; 8.2% and hepatocellular carcinomas; 4.4%). Leukemias and lymphomas accounted for 9.2% of cases, whereas sarcomas accounted for 5.1% of cases.

CONCLUSION: Infection-related and noninfection-related cancers cause most mortality in UPTH. The 5[th] decade was the most commonly affected, while female breast was the single most involved organ. Breast, prostate and hematolymphoid malignancies are common causes of CM with death from breast occurring earliest. Majority of the deceased were educated, working-class urban dwellers. More advocacies on public acceptance of cancer screening and cancer preventive lifestyles as well as governments' improvement on workforce training and treatment infrastructure will improve the current CM profile in Port Harcourt.}, } @article {pmid31839814, year = {2019}, author = {Li, D and Zhong, C and Cheng, Y and Zhu, N and Tan, Y and Zhu, L and Xu, D and Yuan, Y}, title = {A Competing Nomogram to Predict Survival Outcomes in Invasive Micropapillary Breast Cancer.}, journal = {Journal of Cancer}, volume = {10}, number = {27}, pages = {6801-6812}, pmid = {31839814}, issn = {1837-9664}, abstract = {Background: Although it is widely accepted that invasive micropapillary carcinoma (IMPC) presents more aggressive behavior and has a higher aggressive behavior, the prognosis of IMPC compared with invasive ductal carcinoma (IDC) remains controversial. We conducted this study to explore gene expression profiles of IMPC and establish a competing nomogram that predicts the survival outcomes across these two groups of patients. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Propensity score matching (PSM) was used to adjust for potential baseline confounding between IMPC and IDC group. The Kaplan-Meier method was used to calculate the occurrence of overall mortality. The Gray method was used to estimate the rate of breast cancer specific death (BCSD). A competing regression model was used to evaluate factors associated with BCSD. A nomogram based on the competing risk regression model was established to predict individual outcomes. IMPC-specific gene expression profiles were explored using microarrays data from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. Results: In this study, 330786 (99.62%) patients with IDC 1247 (0.38%) patients with IMPC were included. Patients with IMPC had more lymph node involvement and a larger tumor size compared with those with IDC. After PSM, many distributional differences were eliminated, showing that the IMPC and IDC group were more similar. Patients with IMPC had a favorable prognosis with statistical significance compared with patients with IDC (overall mortality HR = 0.68; 95%CI, 0.53-0.86; P = 0.002). Based on Gray method, patients with IMPC had a favorable prognosis with significant statistical significance compared with patients with IDC (BCSD SHR = 0.64; 95%CI, 0.47-0.88; P = 0.006). Multivariate analysis based on competing risk model demonstrated that IMPC was a favorable independent factor for BCSD. The nomogram could accurately predict BCSD with a high internal and external validated C-index (0.835, 0.818 respectively). A total of 53 upregulated differentially expressed genes (DEGs) and 40 downregulated DEGs of IMPC was identified. The GO analysis results showed that downregulated DEGs were significantly enriched in extracellular structure organization, extracellular matrix, cell-substrate adhesion junction. KEGG analysis of selective gene sets shows that downregulated DEGs significantly enriched for processes related to carbon metabolism, Rap1 signaling pathway. Conclusion: In the current study, IMPC accounted for 0.38% of the entire cohort. IMPC was found to be a favorable independent prognostic factor. The present study identified gene expression profiles and signal pathways of IMPC. The developed nomogram can help the oncologists to predict individual outcomes more accurately.}, } @article {pmid31839176, year = {2020}, author = {Crown, A and Rocha, FG and Grumley, JW}, title = {Intraoperative radiation therapy in early-stage breast cancer: Presence of lobular features is not associated with increased rate of requiring additional therapy.}, journal = {American journal of surgery}, volume = {220}, number = {1}, pages = {161-164}, doi = {10.1016/j.amjsurg.2019.11.017}, pmid = {31839176}, issn = {1879-1883}, mesh = {Biopsy ; Brachytherapy/*methods ; Breast/*diagnostic imaging/surgery ; Breast Neoplasms/diagnosis/*therapy ; Female ; Follow-Up Studies ; Humans ; Intraoperative Period ; Mastectomy/*methods ; Middle Aged ; *Neoplasm Staging ; Prospective Studies ; Radiotherapy, Adjuvant/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: There is a paucity of data regarding the application of IORT to the treatment of carcinomas with lobular features.

METHODS: This study includes women with invasive breast cancer who underwent breast conservation in combination with IORT from February 2011 to October 2016. Patients whose final pathology did not satisfy inclusion criteria or had inadequate margins were recommended to undergo additional therapy (AT) with WBRT as well as re-excision of inadequate margins.

RESULTS: 243 invasive breast cancers were treated with IORT. The lobular features (LF) group comprised 62 patients and the invasive ductal carcinoma (IDCA) group consisted of 172 patients. Rate of AT was similar between groups (LF 19 patients, 30.6%, vs IDCA 56 patients, 32.6%, p = 0.87) groups. Lobular histology was not associated with a need for AT. Local recurrence rate for the cohort was 1.2% with a median follow up of 46 months. There was no difference in recurrence or survival after 46 months of follow-up.

CONCLUSIONS: IORT is an effective treatment option for well-selected patients with early breast cancer and can be considered for patients with lobular histology.}, } @article {pmid31836680, year = {2020}, author = {McDonald, ES and Doot, RK and Young, AJ and Schubert, EK and Tchou, J and Pryma, DA and Farwell, MD and Nayak, A and Ziober, A and Feldman, MD and DeMichele, A and Clark, AS and Shah, PD and Lee, H and Carlin, SD and Mach, RH and Mankoff, DA}, title = {Breast Cancer [18]F-ISO-1 Uptake as a Marker of Proliferation Status.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {61}, number = {5}, pages = {665-670}, pmid = {31836680}, issn = {1535-5667}, support = {K01 DA040023/DA/NIDA NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; UL1 TR000003/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biological Transport ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnostic imaging/*metabolism/*pathology ; Cell Proliferation ; Female ; Humans ; Middle Aged ; Positron-Emission Tomography ; }, abstract = {The σ2 receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-[18]F-fluoroethoxy)-5-methylbenzamide ([18]F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of [18]F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether [18]F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT02284919) between March 2015 and January 2017. Each received an injection of 278-527 MBq of [18]F-ISO-1 and then underwent PET/CT imaging of the breasts 50-55 min later. In vivo uptake of [18]F-ISO-1 was quantitated by SUVmax and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUVmax (median, 2.0 g/mL; range, 1.3-3.3 g/mL), partial-volume-corrected SUVmax, and SUV ratios were tested against Ki-67. Tumors stratified into the high-Ki-67 (≥20%) group had SUVmax greater than the low-Ki-67 (<20%) group (P = 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ = 0.46, P = 0.01, n = 29). Partial-volume-corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ = 0.51, P = 0.02, n = 21). Tumor-to-normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P > 0.05). Conclusion:[18]F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.}, } @article {pmid31833179, year = {2020}, author = {Yamamoto, A and Kato, M and Hattori, K and Naito, Y and Tochigi, K and Sano, T and Kawanishi, H and Ishikawa, T and Yuba, T and Hattori, R and Gotoh, M and Tsuzuki, T}, title = {Propensity score-matched comparison of docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant intraductal carcinoma of the prostate.}, journal = {BJU international}, volume = {125}, number = {5}, pages = {702-708}, doi = {10.1111/bju.14970}, pmid = {31833179}, issn = {1464-410X}, mesh = {Administration, Oral ; Aged ; Androstenes/*administration & dosage ; Antineoplastic Agents/administration & dosage ; Benzamides ; Biopsy ; Docetaxel/*administration & dosage ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Humans ; Male ; Nitriles ; Phenylthiohydantoin/administration & dosage/*analogs & derivatives ; *Propensity Score ; Prostate/*diagnostic imaging ; Prostatic Neoplasms, Castration-Resistant/diagnosis/*drug therapy ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with intraductal carcinoma of the prostate (IDC-P) using a propensity score-matched analysis.

PATIENTS AND METHODS: We retrospectively identified 309 patients with CRPC from February 2007 to February 2016 at Nagoya University and its affiliated hospitals. All patients received initial androgen-deprivation therapy (ADT). After progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as first-line life-prolonging therapy. Docetaxel (70-75 mg/m[2]) every 3 weeks vs enzalutamide (160 mg) once daily orally or abiraterone (1 g) once daily plus prednisone (5 mg) twice daily orally was administered. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis. A propensity score analysis with a 1:1 ratio using an optimal matching algorithm was used to adjust for confounding factors.

RESULTS: Overall, 234 patients were analysed. Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 vs 58.3 months in the ARAT group (P = 0.03). For patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (P = 0.01), and there was no significant difference in each group, as in patients without IDC-P (P = 0.67). A multivariate analysis showed that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first-line treatment for CRPC were independent prognostic factors for OS.

CONCLUSION: Administration of ARAT as the first-line treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.}, } @article {pmid31832446, year = {2019}, author = {Yaghoobi, H and Azizi, H and Banitalebi-Dehkordi, M and Mohammad Rezaei, F and Arsang-Jnag, S and Taheri, M and Ghafouri-Fard, S}, title = {Beta-Secretase 1 (BACE1) Is Down-Regulated in Invasive Ductal Carcinoma of Breast.}, journal = {Reports of biochemistry & molecular biology}, volume = {8}, number = {2}, pages = {200-207}, pmid = {31832446}, issn = {2322-3480}, abstract = {BACKGROUND: The enzyme beta-secretase 1 (BACE1) and its antisense transcript (BACE1-AS) have been implicated in the pathogenesis of Alzheimer's disease. Moreover, several lines of evidence point to their contribution in tumorigenesis.

METHODS: In the present study, we evaluated expression of BACE1 mRNA (BACE1) and BACE1-AS in 54 breast cancer tissues and 54 adjacent non-cancerous tissues (ANCTs) from the same patients using quantitative real-time PCR.

RESULTS: BACE1 was significantly down-regulated in tumoral tissues compared with ANCTs, while BACE1- AS expression was not significantly different between tumoral tissues and ANCTs. The Bayesian Multilevel model showed a significant difference in BACE1 expression between stage 1 and 2 cancers after age-effect adjustments. BACE1-AS expression was significantly greater in ER-positive than in ER-negative samples (P=0.01). BACE1 and BACE1-AS expression were not correlated with patient ages in any sample sets.

CONCLUSION: Significant correlations were detected between expression of these genes in both tumoral tissues and ANCTs. The current study provides evidence for differential BACE1 expression in breast tissues and suggests further assessment of the role of BACE1 in the pathogenesis of cancer.}, } @article {pmid31831939, year = {2019}, author = {Adejumo, AA and Ajamu, OJ and Akanbi, OO and Onwukwe, JC and Adeosun, OA and Omoregie, PO and Amos, A and Garba, Y and Koroye, OF and Garba, SE}, title = {Epidemiology and Challenges of Managing Breast Cancer in Keffi, North-Central Nigeria: A Preliminary Report.}, journal = {Nigerian medical journal : journal of the Nigeria Medical Association}, volume = {60}, number = {4}, pages = {193-197}, pmid = {31831939}, issn = {0300-1652}, abstract = {BACKGROUND: Breast cancer is now the commonest female malignancy worldwide. The prognosis of such depends on the histopathological type, biological behavior, stage at presentation, availability of adequate oncological services.

AIMS AND OBJECTIVES: The aim of this this study is to evaluate the statistics and challenges of breast cancer management in the study centre and compare with other centres.

MATERIALS AND METHODS: This is a prospective, descriptive study that spanned over a period of 4 years (January 2015-December 2018). The study was carried out in the General surgery division of the Surgery Department of the Federal Medical Centre, Keffi.

RESULTS: A total of 199 patients were recruited into this study out of which 196 (98.25%) were females and 3 (1.5%) were males. Their age ranged between 20-60 years. The commonest histopathological variant diagnosed is invasive ductal carcinoma (NOS). Early presentation was seen in 54 (<30%) while 145 (>70%) patients had late clinical presentation.

CONCLUSION: Diagnosing and managing breast cancers successfully are mitigated my myriads of factors. Public awareness and provision of adequate care facilities will improve overall survival.}, } @article {pmid31831760, year = {2019}, author = {Manca, M and Glowatzki, E and Roberts, DC and Fridman, GY and Aplin, FP}, title = {Ionic direct current modulation evokes spike-rate adaptation in the vestibular periphery.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {18924}, pmid = {31831760}, issn = {2045-2322}, support = {R01 DC012957/DC/NIDCD NIH HHS/United States ; R01DC009255//U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/International ; R01DC006476//U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)/International ; R01 NS092726/NS/NINDS NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; *Adaptation, Physiological ; Animals ; Female ; Ion Transport/physiology ; Male ; Mice ; Mice, Transgenic ; *Models, Neurological ; Vestibular Nerve/*physiology ; Vestibule, Labyrinth/*physiology ; }, abstract = {Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.}, } @article {pmid31824803, year = {2019}, author = {Manthri, S and Singal, S and Youssef, B and Chakraborty, K}, title = {Long-time Response with Ado-trastuzumab Emtansine in a Recurrent Metastatic Breast Cancer.}, journal = {Cureus}, volume = {11}, number = {10}, pages = {e6036}, pmid = {31824803}, issn = {2168-8184}, abstract = {Breast cancer is the most common cancer in a woman with a five-year survival of patients with metastatic disease is estimated at 23%. Ado-trastuzumab emtansine (T-DM1) is a HER2-antibody drug conjugate currently approved for the treatment of HER2-positive pre-treated metastatic breast cancer (BC). We report a case of recurrent metastatic breast cancer with unusually lengthy progression-free survival (PFS) on T-DM1 chemotherapy. She was diagnosed with Triple Positive Stage IIIC multifocal invasive ductal carcinoma of the left breast. After completing neoadjuvant chemotherapy, she underwent a bilateral mastectomy. Final pathology showed partial response. Postoperatively, she received adjuvant chemotherapy and radiation therapy. She was started on Q21 days trastuzumab following completion of adjuvant chemotherapy. Systemic imaging showed liver lesions and biopsy confirmed recurrence. She was started on T-DM1, endocrine therapy with anastrozole was continued. She is currently status post 45 cycles. T-DM1 was approved for the treatment (single-agent) of HER2-positive, metastatic BC based on phase III data from the EMILIA and TH3RESA study. Median PFS in the T-DM1 arm was 9.6 months. Herein, we present a case of a woman with recurrent triple positive metastatic BC with a lengthy progression-free survival on T-DM1 chemotherapy.}, } @article {pmid31820860, year = {2019}, author = {Xu, D and Hou, L}, title = {Clinicopathologic characteristics of mixed epithelial/mesenchymal metaplastic breast carcinoma (carcinosarcoma): a meta-analysis of Chinese patients.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {70}, number = {3}, pages = {174-182}, doi = {10.5114/pjp.2019.90393}, pmid = {31820860}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinosarcoma/*pathology ; China ; Female ; Humans ; Lymphatic Metastasis ; Metaplasia ; Middle Aged ; Survival Rate ; }, abstract = {UNLABELLED: Breast carcinosarcoma is a rare and aggressive subtype of metaplastic breast cancer. Data focusing on breast carcinosarcoma is limited. The purposes of this study are to describe the clinicopathological features of breast carcinosarcoma and to evaluate post-surgical outcomes.

MATERIAL AND METHODS: All case reports about breast carcinosarcoma in China were collected from eligible papers published in Chinese core periodicals between 1990 and 2015 with key words of breast carcinosarcoma, breast cancer, carcinosarcoma, or metaplastic carcinoma. The survival rates, clinical behaviour, and pathological characteristics were analysed.

RESULTS: The mean age of the cohort of 215 patients was 53 years (range, 25-82 years). The tumour size ranged from 2.5 cm to 18 cm. The incidence of pathologically confirmed lymph node metastases was 30.81%. The epithelial component in a tumour may be composed of invasive ductal carcinoma (84.21%), squamous cell carcinoma (7.89%), lipid-rich carcinoma (6.58%), or adenocarcinoma (1.31%). Mesenchymal components may contain different elements ranging from fibrosarcoma (63.16%) to chondrosarcoma (19.73%), osteosarcoma (9.21%), liposarcoma (3.95%), or leiomyosarcoma (3.95%). The five-year survival of the breast carcinosarcoma in 149 patients is 62.6% (CI: 54.9%~0.703%).

CONCLUSIONS: Breast carcinosarcoma is a rare subtype of metaplastic breast cancer. It is characterised by large tumour size, higher rates of axillary nodal involvement, higher rates of both local and distant recurrence, and is difficult to diagnose with preoperative core needle biopsies. Adjuvant treatment after surgical operation may improve the five-year OS of patients with breast carcinosarcoma.}, } @article {pmid31819783, year = {2019}, author = {Fitzpatrick, MB and Rendi, MH and Kiviat, NB and Toure, P and Dem, A and Sow, PS and Hawes, SE and Feng, Q and Allison, KH}, title = {Pathology of Senegalese breast cancers.}, journal = {The Pan African medical journal}, volume = {34}, number = {}, pages = {67}, pmid = {31819783}, issn = {1937-8688}, mesh = {Adult ; Biopsy ; Breast Neoplasms/diagnosis/epidemiology/*pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; *Premenopause ; Prospective Studies ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Senegal/epidemiology ; Triple Negative Breast Neoplasms/diagnosis/epidemiology/*pathology ; }, abstract = {INTRODUCTION: Breast cancer is among the most common cancers among women in most of Africa. However, features of histologically confirmed breast cancers presenting in specific regional populations is limited. Our study describes the clinic-pathologic features of invasive breast cancer diagnosed in women undergoing biopsy for a clinically apparent mass in Senegal, West Africa.

METHODS: A prospective cohort of 522 Senegalese women presenting consecutively to Dantec Hospital (University of Dakar Tumor Institute) with a breast mass were included in the study cohort. Demographic data was collected by survey and 197 (37.7%) core needle biopsy-confirmed invasive breast cancers available for review were subsequently centrally reviewed at the University of Washington in Seattle to further to characterize the pathologic features and to perform immunohistochemistry for ER/PR and HER2.

RESULTS: Seventy six (76.1%) of the 522 Senegalese women presenting for biopsy of a clinically apparent breast mass were diagnosed with invasive breast cancer. The average age of a woman with invasive cancer was 46 years old, and most (83%) presented with Stage III or IV disease. The predominant histologic subtype among the 197 biopsy-confirmed cancers was invasive ductal carcinoma (98%), with few cases of invasive lobular carcinoma (2%). Cancers were classified into four clinically relevant treatment IHC groups by combined ER/PR status and HER2 status as follows: ER-/PR-, HER2- (n=92; 46.7%), ER-/PR-, HER2+ (n=20; 10.1%), ER+/PR+, HER2- (n=76; 38.6%) and ER+/PR+, HER2+ (n=9; 4.6%). Age at time of diagnosis was similar between these four subgroups although more HER2 positive cases were pre-menopausal (p=0.05). Stage of disease at presentation differed by IHC group (p=0.008), with HER2+ cancers significantly more likely to present with stage IV disease than other IHC groups, including ER-/PR-, HER2-. There were no significant differences between groups by age group, ethnicity, place of residence or birth, or parity.

CONCLUSION: Our analysis of breast cancer cases in Senegal shows a distribution of clinically relevant IHC groups like that seen in the few prior studies of breast cancer in West Africa, with higher frequencies of triple negative cancers than in most United States and European populations. Mean age at presentation, delayed presentation, and genetic/regional risk factors likely influence these differences. A better understanding of the frequencies of the pathologic features of breast cancers in the West African population may help guide future genetic studies as well as appropriate clinical management of breast cancer in these populations.}, } @article {pmid31817994, year = {2019}, author = {Kranzler, Y and Parag, Y and Davidovitch, N}, title = {Public Health from the Middle-Out: A New Analytical Perspective.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {24}, pages = {}, pmid = {31817994}, issn = {1660-4601}, mesh = {Cooperative Behavior ; Delivery of Health Care ; Female ; *Health Policy ; Humans ; Interviews as Topic ; Israel ; Male ; Obesity ; *Public Health ; Public Policy ; Qualitative Research ; }, abstract = {Obstacles to collaborative public health frameworks such as Health in All Policies continue to emerge. Partnership-based public health programs present opportunities to study how public servants and practitioners address these barriers in real time. To this end, we utilized "Middle-Out," a socio-technical analytical approach that highlights the importance of Middle Actors-stakeholders positioned between policymakers and grassroots-to policy diffusion, innovation and collaboration in public health. We conducted participatory observation in administrative settings of Israel's National Program to Promote Active, Healthy Lifestyle, 30 stakeholder interviews and document analysis. We examined two dimensions of impact from the Middle-Out: Directions of Influence-Middle-Up, Middle-Down and Sideways, and Modes of Influence-Enabling, Mediating and Aggregating. Through Middle-Out's lens, our analysis transcends visible benchmarks such as legislation and macro-level resource-allocation, focusing, instead, on elusive administrative spaces within which Middle Actors shape policies, steer funding and facilitate continuity. Incorporating Middle-Out into public health's conceptual toolbox, we conclude, can improve understanding of complex public health policy arenas, increase recognition of critical socio-technical changemakers and catalyze more effective design of policy tools and strategies that specifically harness Middle Actors' strengths and qualities.}, } @article {pmid31815728, year = {2020}, author = {Zhou, WP and Zan, XY and Hu, XY and Liu, X and Sudarshan, SKP and Yang, SD and Guo, YJ and Fang, XM}, title = {Characterization of breast lesions using diffusion kurtosis model-based imaging: An initial experience.}, journal = {Journal of X-ray science and technology}, volume = {28}, number = {1}, pages = {157-169}, doi = {10.3233/XST-190590}, pmid = {31815728}, issn = {1095-9114}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Male ; Middle Aged ; Prospective Studies ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the characterization of breast lesions using diffusion kurtosis model-based imaging.

METHODS: This prospective study included 120 consecutive patients underwent preoperative DCE-MRI examinations and multi-b-value diffusion-weighted imaging (DWI). Among them, 88 malignant lesions and 44 benign lesions were detected, 56 normal fibroglandular breast tissue were selected as normal control. Conventional apparent diffusion coefficient (ADC), DKI-based parameters mean kurtosis (MK) and mean diffusivity (MD) were analyzed by lesions types and histological subtypes using one-way ANOVA and receiver operating characteristic (ROC) curve.

RESULTS: (1) The malignant group showed significantly lower ADC and MD (1.07±0.32×10-3 mm2/s and 1.30±0.40×10-3 mm2/s, respectively) and higher MK (0.87±0.18) than those in the benign group (1.29±0.26×10-3 mm2/s, 1.62±0.31×10-3 mm2/s and 0.67±0.18) and control group (1.67±0.33×10-3 mm2/s, 2.24±0.28×10-3 mm2/s and 0.52±0.08) with all P < 0.001. (2) Areas under ROC curve (AUC) for diagnosing malignant lesions were 0.936 for MD, 0.911 for MK and 0.897 for ADC, respectively. AUC for MD was significantly higher than that for ADC (P = 0.015). The optimal cut-off value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were as follow: ADC = 1.18×10-3mm2/s, 78.3%, 93.2%, 81.2%, 81.6%, 81.4%; MD = 1.48×10-3mm2/s, 82.2%, 98.3%, 84.4%, 87.8%, 86.2%; MK = 0.78, 91.5%, 85.3%, 89.0%, 85.8%, 87.2%. (3) Invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and mucinous adenocarcinoma also showed significant differences among ADC, MD and MK (with P < 0.05).

CONCLUSIONS: MR-DKI parameters enable to improve breast lesion characterization and have diagnostic potential applying to different pathological subtypes of breast cancers.}, } @article {pmid31814295, year = {2020}, author = {Li, Y and Su, P and Wang, Y and Zhang, H and Liang, Y and Zhang, N and Song, X and Li, X and Li, J and Yang, Q}, title = {Impact of histotypes on preferential organ-specific metastasis in triple-negative breast cancer.}, journal = {Cancer medicine}, volume = {9}, number = {3}, pages = {872-881}, pmid = {31814295}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*epidemiology/secondary ; Brain Neoplasms/*epidemiology/secondary ; Breast/pathology ; Carcinoma, Ductal, Breast/*epidemiology/secondary ; Carcinoma, Lobular/*epidemiology/secondary ; Female ; Humans ; Liver Neoplasms/*epidemiology/secondary ; Lung Neoplasms/*epidemiology/secondary ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; SEER Program/statistics & numerical data ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: The distant metastasis was the most predictive characters of poor prognosis for triple-negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis.

METHODS: Using the 2010-2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi-squared test. Logistic regression was used for identification of predictive factors. The log-rank testing was utilized with disease-specific survival (DSS) and overall survival (OS) as the primary outcomes.

RESULTS: A total of 23 270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis.

CONCLUSION: Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC.}, } @article {pmid31812891, year = {2020}, author = {Lin, S and Liu, C and Tao, Z and Zhang, J and Hu, X}, title = {Clinicopathological characteristics and survival outcomes in breast carcinosarcoma: A SEER population-based study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {49}, number = {}, pages = {157-164}, pmid = {31812891}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Carcinosarcoma/*mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Propensity Score ; Proportional Hazards Models ; SEER Program ; Triple Negative Breast Neoplasms/mortality/pathology ; Tumor Burden ; }, abstract = {OBJECTIVES: Carcinosarcoma of the breast is a rare disease. Its clinicopathological features and prognosis are not well defined. The aim of this study was to compare the clinicopathological features and clinical outcome between breast carcinosarcoma and breast invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: Patients with breast carcinosarcoma and breast IDC were identified through the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Then a comparison was conducted between these two groups. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences. The Cox proportional hazard model was used to identify potential prognostic factors of breast carcinosarcoma.

RESULTS: In total, we identified 63 patients with breast carcinosarcoma and 200,596 cases with breast IDC. Comparing with IDC, breast carcinosarcoma was significantly correlated with higher grading, higher staging, larger tumor size, lower lymph node involvement, and a higher proportion of triple negative breast cancer (TNBC), suggesting a significantly worse clinical outcome. After adjusting for the uneven clinicopathological variables with PSM, significant differences were still observed between these two histology types. Subgroup analysis further showed that carcinosarcoma-TNBC has an inferior clinical outcome compared with IDC-TNBC. Finally, we identified independent prognostic factors, namely, stage, tumor size, and distant metastasis.

CONCLUSION: It is concluded that breast carcinosarcoma has distinct clinicopathological features and a significantly worse clinical outcome than common IDC.}, } @article {pmid31809502, year = {2019}, author = {Pick, FC and Fish, KE and Biggs, CA and Moses, JP and Moore, G and Boxall, JB}, title = {Application of enhanced assimilable organic carbon method across operational drinking water systems.}, journal = {PloS one}, volume = {14}, number = {12}, pages = {e0225477}, pmid = {31809502}, issn = {1932-6203}, mesh = {Carbon/*analysis/metabolism ; Drinking Water/chemistry/microbiology/*standards ; Flow Cytometry/methods ; Organic Chemicals/*analysis/metabolism ; Pseudomonas fluorescens/metabolism ; Reproducibility of Results ; Spirillum/metabolism ; Water Microbiology/*standards ; Water Purification ; Water Quality/*standards ; }, abstract = {Assimilable organic carbon (AOC) is known to correlate with microbial growth, which can consequently degrade drinking water quality. Despite this, there is no standardised AOC test that can be applied to drinking water distribution systems (DWDS). Herein we report the development of a quick, robust AOC that incorporates known strains Pseudomonas fluorescens strain P-17 and Spirillum strain NOX, a higher inoculum volume and enumeration using flow cytometry to generate a quicker (total test time reduced from 14 to 8 days), robust method. We apply the developed AOC test to twenty drinking water treatment works (WTW) to validate the method reproducibility and resolution across a wide range of AOC concentrations. Subsequently, AOC was quantified at 32 sample points, over four DWDS, for a year in order to identify sinks and sources of AOC in operative networks. Application of the developed AOC protocol provided a previously unavailable insight and novel evidence of pipes and service reservoirs exhibiting different AOC and regrowth behaviour. Observed correlations between AOC and microbial growth highlight the importance of monitoring AOC as an integral part of managing drinking water quality at the consumers tap.}, } @article {pmid31808945, year = {2020}, author = {Assor, A and Kanat-Maymon, Y and Keren-Pariente, S and Katz, I}, title = {You should know me better: Parents' temperament-insensitivity has negative motivational effects on Bedouin and Jewish adolescents.}, journal = {Journal of personality}, volume = {88}, number = {5}, pages = {874-891}, doi = {10.1111/jopy.12532}, pmid = {31808945}, issn = {1467-6494}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Arabs/*psychology ; Female ; Humans ; Jews/*psychology ; Male ; *Motivation ; *Parent-Child Relations ; Parents/psychology ; Shyness ; Surveys and Questionnaires ; *Temperament ; }, abstract = {OBJECTIVE: We studied a recently conceptualized aspect of autonomy-support and suppression, not examined so far: Sensitivity to temperament dispositions. Based on self-determination theory, we hypothesized that, across cultures, disposition-frustrating decisions would have similar negative effects on adolescents' intrinsic motivation to participate in decision-related activities, and these negative effects would not be mitigated in collectivist-hierarchical cultures, when parents make the decision.

METHOD: In Study 1 (n = 570, mean age = 15.2 years), Bedouin and Jewish adolescents were presented with work modes frustrating or supporting their shyness and sociability dispositions. For example, in one frustrating work mode condition, shy participants expected to work with strangers. Then, participants indicated their intrinsic motivation to participate in the activities. Study 2 (n = 278 Bedouins and Jews, mean age = 14.9 years) was an experiment using self-report and projective measures, examining the effects of temperament-supporting versus frustrating work modes, ostensibly chosen by parents, on adolescents' intrinsic motivation to participate in relevant activities.

RESULTS: Both studies showed that, across cultures, frustrating work modes had negative effects on participants' intrinsic motivation. These effects were not moderated by cultural background.

CONCLUSIONS: Results suggest that belonging to a collectivist Bedouin culture endorsing deference and obedience to parental authority does not mitigate the negative motivational effect of parents' temperament-insensitivity, and this type of autonomy-support is important across cultures.}, } @article {pmid31806636, year = {2019}, author = {Abdulla, HA and Almarzooq, R and Alrayes, A}, title = {Synchronous breast and colon cancer: the importance of multidisciplinary team cancer meetings.}, journal = {BMJ case reports}, volume = {12}, number = {12}, pages = {}, pmid = {31806636}, issn = {1757-790X}, mesh = {Adenocarcinoma/*diagnosis/pathology/therapy ; Breast Neoplasms/*diagnosis/pathology/therapy ; Carcinoma, Ductal, Breast/*diagnosis/pathology/therapy ; Colonic Neoplasms/*diagnosis/pathology/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Humans ; *Interdisciplinary Communication ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/pathology/therapy ; }, abstract = {A 58-year-old female patient presented with left breast lump. Mammography and ultrasonography were performed, which reported lesions suspicious of malignancy in the left breast and axilla. Core biopsy of the lesions revealed invasive ductal carcinoma with axillary lymph node metastasis. Staging CT scan (thorax, abdomen and pelvis) identified a coexisting neoplasm in the ascending colon. Colonoscopy was performed and the tumour in the ascending colon was biopsied. Histopathological examination revealed adenocarcinoma. In the multidisciplinary team cancer meeting, it was decided to treat the breast cancer first and then the colon cancer, followed by adjuvant chemotherapy. In the first operation, left modified radical mastectomy was performed. Two weeks after her initial operation, the patient underwent laparoscopic right hemicolectomy. Postoperatively, the patient did not develop any complications and was referred to oncology for chemotherapy.}, } @article {pmid31800757, year = {2019}, author = {Cáceres, CVBL and Vargas, PA and Sánchez-Romero, C and Bunn, BK and Heerden, WFPV and Fonseca, FP}, title = {Distribution of Dendritic Cells in AIDS-Associated Oral Kaposi's Sarcoma.}, journal = {Brazilian dental journal}, volume = {30}, number = {6}, pages = {617-625}, doi = {10.1590/0103-6440201902599}, pmid = {31800757}, issn = {1806-4760}, mesh = {*Acquired Immunodeficiency Syndrome ; Dendritic Cells ; *Herpesvirus 8, Human ; Humans ; Retrospective Studies ; *Sarcoma, Kaposi ; }, abstract = {The aim of this study was to determine if the distribution of Langerhans cells (LC) and interstitial dendritic cells (IDC) is altered in AIDS-associated oral Kaposi's sarcoma when compared to HIV-negative highly vascular oral lesions. Fifty-one cases of AIDS-associated oral Kaposi's sarcoma and 20 of highly vascular oral lesions were retrospectively retrieved. All cases of Kaposi's sarcoma were confirmed with immunoreactions against CD34 and HHV-8. Clinical data regarding sex, age and lesions location were obtained from pathology reports. Immunohistochemistry against CD207 (immature dendritic cells) and CD83 (mature dendritic cells) were done. LC were in the epithelium and IDC in the stroma. CD207+ cells predominated in the epithelium of the lesions, whereas CD83+ cells predominated in their stromal compartment. Kaposi's sarcoma had a lower CD207+ immature LC count (p=0.02) and an increased CD207+ IDC than highly vascular oral lesions (p<0.001). Moreover, Kaposi's sarcoma also showed an increased number of mature CD83+ IDC than highly vascular oral lesions (p<0.001). There were significant alterations in the distribution of LC and IDC in AIDS-associated Kaposi's sarcoma when compared to HIV-negative vascular oral lesions, suggesting that changes in their concentrations may play a role in the pathogenesis of Kaposi's sarcoma.}, } @article {pmid31800564, year = {2020}, author = {Kaviani, A and Tabary, M and Zand, S and Araghi, F and Nouraie, M}, title = {A Study on Breast Reconstruction in a Developing Country: A Comprehensive Evaluation of the Techniques and Oncologic Outcomes.}, journal = {Annals of plastic surgery}, volume = {84}, number = {5}, pages = {512-517}, doi = {10.1097/SAP.0000000000002125}, pmid = {31800564}, issn = {1536-3708}, mesh = {*Breast Neoplasms/surgery ; Developing Countries ; Female ; Humans ; Iran/epidemiology ; *Mammaplasty ; Retrospective Studies ; Surgical Flaps ; }, abstract = {BACKGROUND: Breast cancer, with an incidence of 33.2 per 100,000 in Iranian population, is considered as the most common cancer in Iranian women. Nowadays, with the increasing survival rates, breast reconstruction has been integrated into surgical techniques of breast cancer treatment. The aim of this study was to evaluate the current status of breast reconstruction in Iranian population.

PATIENTS AND METHODS: This retrospective study was conducted in Imam Hospital between January 2008 and June 2018. All the patients underwent breast reconstruction surgery. The trend of reconstruction and complication rates were 2 major outcomes. Logistic regression model was used to predict complications. Student t test was used to compare means.

RESULTS: Fifty-five patients underwent 60 autologous breast reconstruction surgeries and 152 patients underwent 193 prosthesis-based reconstruction surgeries. Most of cases were invasive ductal carcinoma ± ductal carcinoma in situ (126 cases, 68%). Among 253 surgeries in 207 patients, 98 cases (38.7%) were 2-stage implant, 91 (36.0%) were 1-stage implant, 3 (1.2%) were acellular dermal matrix + prosthesis, 31 (12.2%) were pedicled transverse rectus abdominis myocutaneous flap, 25 (9.8%) were latissimus dorsi flap ± prosthesis, and 4 (15.8%) were latissimus dorsi flap. Among prosthesis-based reconstructions, chemotherapy could predict the occurrence of complications (odds ratio, 2.87; 95% CI, 1.07-7.68), whereas none of these factors could predict the occurrence of complications in autologous reconstructions. The most prevalent complication was seroma formation (48.5% of all complications). Overall complication rates (including major and minor) were higher among autologous reconstructions compared with prosthesis-based reconstructions (45.8% and 21.1%, respectively, P < 0.001).

CONCLUSIONS: The trend of breast reconstruction is changing in Islamic Republic of Iran as a developing country. Implant-based reconstruction has surpassed autologous reconstructions in recent years. In terms of complications, we observed higher rates among autologous reconstructions.}, } @article {pmid31795110, year = {2019}, author = {Gonzalez, LF and Vidal, I and Valera, F and Nogales, B and Sanchez-Aguero, V and Lopez, DR}, title = {Transport-Layer Limitations for NFV Orchestration in Resource-Constrained Aerial Networks.}, journal = {Sensors (Basel, Switzerland)}, volume = {19}, number = {23}, pages = {}, pmid = {31795110}, issn = {1424-8220}, support = {777137//European Commission/ ; TEC2016-76795-C6-3-R//Spanish Ministry of Economy and Competitiveness/ ; }, abstract = {In this paper, we identify the main challenges and problems related with the management and orchestration of Virtualized Network Functions (VNFs) over aerial networks built with Small Unmanned Aerial Vehicles (SUAVs). Our analysis starts from a reference scenario, where several SUAVs are deployed over a delimited geographic area, and provide a mobile cloud environment that supports the deployment of functions and services using Network Functions Virtualization (NFV) technologies. After analyzing the main challenges to NFV orchestration in this reference scenario from a theoretical perspective, we undertake the study of one specific but relevant aspect following a practical perspective, i.e., the limitations of existing transport-layer solutions to support the dissemination of NFV management and orchestration information in the considered scenario. While in traditional cloud computing environments this traffic is delivered using TCP, our simulation results suggest that using this protocol over an aerial network of SUAVs presents certain limitations. Finally, based on the lessons learned from our practical analysis, the paper outlines different alternatives that could be followed to address these challenges.}, } @article {pmid31791269, year = {2019}, author = {Lee, CH and Hsieh, JC and Wu, TM and Yeh, TS and Wang, HM and Lin, YC and Chen, JS and Lee, CL and Huang, WK and Hung, TM and Yen, TT and Chan, SC and Chou, WC and Kuan, FC and Hu, CC and Chang, PH}, title = {Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1167}, pmid = {31791269}, issn = {1471-2407}, support = {CMRPG2D0171, CMRPG2D0172, CMRPG2G0681, CMRPG2G0682//Chang Gung Memorial Hospital/ ; CMRPG2D0173//Chang Gung Memorial Hospital/ ; PMRPG3G0791, CMRPG3G0771, CORPG3F0731, CMRPG3E1631-33//Chang Gung Memorial Hospital/ ; CMRPG3G1131-1133, CMRPG3H0871-73//Chang Gung Memorial Hospital/ ; MOST-108-2628-B-182A-001//Ministry of Science and Technology, Taiwan/ ; MOST-107-2314-B-182-053, MOST-104-2314-B-182-031-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {AC133 Antigen/immunology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology ; Cell Count ; Female ; Humans ; Liquid Biopsy ; Middle Aged ; Neoplastic Cells, Circulating/immunology/*pathology ; Neoplastic Stem Cells/immunology/*pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.

METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM[+]Hoechst[+]CD45[-] cells and cCSCs as CD133[+]EpCAM[+]Hoechst[+]CD45[-] cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.

RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.

CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.}, } @article {pmid31789065, year = {2020}, author = {Tijani, S and Sharma, K and Yuen, H and Shaaban, A}, title = {Metastatic "Ductal Carcinoma In Situ-Like" Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature.}, journal = {International journal of surgical pathology}, volume = {28}, number = {4}, pages = {436-439}, doi = {10.1177/1066896919888744}, pmid = {31789065}, issn = {1940-2465}, mesh = {Axilla ; Biomarkers, Tumor/analysis/metabolism ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Diagnosis, Differential ; Diagnostic Errors/prevention & control ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Mammography ; Mastectomy ; Middle Aged ; }, abstract = {Metastatic breast cancer resembling ductal carcinoma in situ (DCIS) is a rare phenomenon. In this article, we present a unique case of metastatic lobular carcinoma with DCIS-like morphology in the left axillary lymph nodes of a 52-year-old female. She presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm tumor in the upper outer quadrant. Microscopic assessment revealed a pleomorphic lobular carcinoma in the lower outer quadrant and a grade 2 invasive ductal carcinoma in the upper outer quadrant. Sixteen of the 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features. Immunohistochemical analysis of the primary and metastatic lobular carcinoma showed no expression of E-cadherin and p63 antibodies. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported. The case suggests that lobular carcinoma can morphologically recreate a primary microenvironment at a distant site and simulate in situ growth. Recognition of this pattern is important to avoid misdiagnosis.}, } @article {pmid31784608, year = {2019}, author = {Marchetti, E and Ripepe, M and Campus, P and Le Pichon, A and Vergoz, J and Lacanna, G and Mialle, P and Héreil, P and Husson, P}, title = {Long range infrasound monitoring of Etna volcano.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {18015}, pmid = {31784608}, issn = {2045-2322}, abstract = {Among ground-based volcano monitoring techniques, infrasound is the only one capable of detecting explosive eruptions from distances of thousands of kilometers. We show how infrasound array analysis, using acoustic amplitude and detection persistency, allows automatic, near-real-time identification of eruptions of Etna volcano (Italy), for stations at distances greater than 500 km. A semi-empirical attenuation relation is applied to recover the pressure time history at the source using infrasound recorded at global scale (>500 km). An infrasound parameter (IP), defined as the product between the number of detections, filtered for the expected back-azimuth of Etna volcano, and range corrected amplitude, is compared with the explosive activity at Etna volcano that was associated with aviation color code RED warnings. This shows that, during favourable propagation conditions, global arrays are capable of identifying explosive activity of Etna 87% of the period of analysis without negative false alerts. Events are typically not detected during unfavourable propagation conditions, thus resulting in a time variable efficiency of the system. We suggest that infrasound monitoring on a global scale can provide timely input for Volcanic Ash Advisory Centres (VAAC) even when a latency of ~1 hour, due to propagation time, is considered. The results highlight the capability of infrasound for near-real-time volcano monitoring at a regional and global scale.}, } @article {pmid31779581, year = {2019}, author = {Luo, K and Wang, S and Fu, Y and Zhou, P and Huang, X and Gu, Q and Li, W and Wang, Y and Hu, F and Liu, S}, title = {Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).}, journal = {BMC genetics}, volume = {20}, number = {1}, pages = {87}, pmid = {31779581}, issn = {1471-2156}, mesh = {Animals ; Carps/genetics/*physiology ; Evolution, Molecular ; Female ; Fish Proteins/genetics ; *Genetic Variation ; Goldfish/genetics/*physiology ; Homeodomain Proteins/*genetics ; Hybridization, Genetic ; Male ; Multigene Family ; Sequence Analysis, DNA/veterinary ; }, abstract = {BACKGROUND: Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.

RESULT: In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.

CONCLUSIONS: Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.}, } @article {pmid31775445, year = {2019}, author = {Lian, J and Li, J and Ma, HX and Wang, LX}, title = {[Synchronous invasive ductal carcinoma and primary lymphoma of breast: report of a case].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {48}, number = {11}, pages = {899-901}, doi = {10.3760/cma.j.issn.0529-5807.2019.11.016}, pmid = {31775445}, issn = {0529-5807}, mesh = {Breast ; *Breast Neoplasms ; Carcinoma, Ductal, Breast ; Humans ; *Lymphoma ; }, } @article {pmid31767582, year = {2019}, author = {Ansbro, ÉM and Biringanine, M and Caleo, G and Prieto-Merino, D and Sadique, Z and Perel, P and Jobanputra, K and Roberts, B}, title = {Management of diabetes and associated costs in a complex humanitarian setting in the Democratic Republic of Congo: a retrospective cohort study.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e030176}, pmid = {31767582}, issn = {2044-6055}, mesh = {*Altruism ; Cohort Studies ; Democratic Republic of the Congo ; Diabetes Mellitus/*economics/*therapy ; Female ; Health Care Costs/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: We aimed to evaluate an Integrated Diabetic Clinic within a Hospital Outpatient Department (IDC-OPD) in a complex humanitarian setting in North Kivu, Democratic Republic of Congo. Specific objectives were to: (1) analyse diabetes intermediate clinical and programmatic outcomes (blood pressure (BP)/glycaemic control, visit volume and frequency); (2) explore the association of key insecurity and related programmatic events with these outcomes; and (3) describe incremental IDC-OPD programme costs.

DESIGN: Retrospective cohort analysis of routine programmatic data collected from January 2014 to February 2017; analysis of programme costs for 2014/2015.

SETTING: Outpatient diabetes programme in Mweso hospital, supported by Médecins sans Frontières, in North Kivu, Demographic Republic of Congo.

PARTICIPANTS: Diabetes patients attending IDC-OPD.

OUTCOME MEASURES: Intermediate clinical and programmatic outcome trends (BP/ glycaemic control; visit volume/frequency); incremental programme costs.

RESULTS: Of 243 diabetes patients, 44.6% were women, median age was 45 (IQR 32-56); 51.4% were classified type 2. On introduction of IDC-OPD, glucose control improved and patient volume and visit interval increased. During insecurity, control rates were initially maintained by a nurse-provided, scaled-back service, while patient volume and visit interval decreased. Following service suspension due to drug stock-outs, patients were less likely to achieve control, improving on service resumption. Total costs decreased 16% from 2014 (€36 573) to 2015 (€30 861). Annual cost per patient dropped from €475 in 2014 to €214 in 2015 due to reduced supply costs and increased patient numbers.

CONCLUSIONS: In a chronic conflict setting, we documented that control of diabetes intermediate outcomes was achievable during stable periods. During insecure periods, a simplified, nurse-led model maintained control rates until drug stock-outs occurred. Incremental per patient annual costs were lower than chronic HIV care costs in low-income settings. Future operational research should define a simplified diabetes care package including emergency preparedness.}, } @article {pmid31765735, year = {2020}, author = {Morimoto, M and Horikoshi, Y and Nakaso, K and Kurashiki, T and Kitagawa, Y and Hanaki, T and Sakamoto, T and Honjo, S and Umekita, Y and Fujiwara, Y and Matsura, T}, title = {Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.}, journal = {Cancer letters}, volume = {470}, number = {}, pages = {149-160}, doi = {10.1016/j.canlet.2019.11.028}, pmid = {31765735}, issn = {1872-7980}, mesh = {Aged ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Signaling System ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Pancreas/pathology ; Pancreatic Neoplasms/mortality/*pathology ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.}, } @article {pmid31760247, year = {2020}, author = {Toğaçar, M and Ergen, B and Cömert, Z}, title = {Application of breast cancer diagnosis based on a combination of convolutional neural networks, ridge regression and linear discriminant analysis using invasive breast cancer images processed with autoencoders.}, journal = {Medical hypotheses}, volume = {135}, number = {}, pages = {109503}, doi = {10.1016/j.mehy.2019.109503}, pmid = {31760247}, issn = {1532-2777}, mesh = {Algorithms ; Artificial Intelligence ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diagnosis, Computer-Assisted/*methods ; Discriminant Analysis ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Linear Models ; Machine Learning ; Neoplasm Invasiveness ; Neural Networks, Computer ; Programming Languages ; Reproducibility of Results ; Sensitivity and Specificity ; Software ; }, abstract = {Invasive ductal carcinoma cancer, which invades the breast tissues by destroying the milk channels, is the most common type of breast cancer in women. Approximately, 80% of breast cancer patients have invasive ductal carcinoma and roughly 66.6% of these patients are older than 55 years. This situation points out a powerful relationship between the type of breast cancer and progressed woman age. In this study, the classification of invasive ductal carcinoma breast cancer is performed by using deep learning models, which is the sub-branch of artificial intelligence. In this scope, convolutional neural network models and the autoencoder network model are combined. In the experiment, the dataset was reconstructed by processing with the autoencoder model. The discriminative features obtained from convolutional neural network models were utilized. As a result, the most efficient features were determined by using the ridge regression method, and classification was performed using linear discriminant analysis. The best success rate of classification was achieved as 98.59%. Consequently, the proposed approach can be admitted as a successful model in the classification.}, } @article {pmid31749246, year = {2020}, author = {Fundytus, A and Saad, N and Logie, N and Roldan Urgoiti, G}, title = {Breast cancer in transgender female-to-male individuals: A case report of androgen receptor-positive breast cancer.}, journal = {The breast journal}, volume = {26}, number = {5}, pages = {1007-1012}, doi = {10.1111/tbj.13655}, pmid = {31749246}, issn = {1524-4741}, mesh = {*Breast Neoplasms/drug therapy/surgery ; Female ; Gender Identity ; Humans ; Male ; Mastectomy ; Middle Aged ; Receptors, Androgen ; *Transgender Persons ; }, abstract = {Highlight the challenges associated with managing breast cancer in female-to-male (FtM) transgender individuals. This is a rare entity, requiring nuanced decision-making regarding surgery as well as adjuvant therapies given the unique hormonal environment seen in individuals taking exogenous androgen as part of their gender identity. Contemporary case report derived from our clinical experience. Discussion focuses on a brief summation of all known cases of female-to-male breast cancer in FtM individuals described in the literature. A 48-year-old FtM transgender individual on exogenous testosterone for 19 years with stage IIA (pT1cN1M0), ER+(8/8), PR+(8/8), Androgen Receptor(AR)+(5%-8%), Her-2-negative invasive ductal carcinoma of the breast. Due to AR positivity in tumor, cessation of testosterone was chosen after careful consideration of potential ramifications from both a cancer treatment as well as gender identity standpoint. Endocrinology consultation reassured the patient that identity affirming changes of facial hair growth and voice depth would persist after cessation of testosterone. Patient did not wish to undergo chemotherapy and as such was treated with combination of radiation to the axilla, adjuvant Anastrozole and testosterone cessation. Although breast cancer is rare in FtM transgender individuals, it can occur. Many FtM individuals take exogenous testosterone. It is important to test the tumor for the androgen receptor as this may have important implications for both gender identity and treatment. Additionally, the mastectomy commonly performed for "top" surgery in this population is not adequate for oncologic control by itself and at present there is no guidance regarding postsurgical screening in this population, especially in those individuals with a strong family history of breast cancer.}, } @article {pmid31749241, year = {2020}, author = {Palicelli, A}, title = {What do we know about the cytological features of pure intraductal carcinomas of the salivary glands?.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {31}, number = {3}, pages = {185-192}, doi = {10.1111/cyt.12790}, pmid = {31749241}, issn = {1365-2303}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Male ; Middle Aged ; Salivary Gland Neoplasms/*pathology ; Salivary Glands/*pathology ; }, abstract = {OBJECTIVE: Intraductal carcinomas (IDCs) are rare, poorly characterised salivary gland tumours. The cytological features of IDCs are even less known. In this paper, a systematic literature review of pure IDCs (without stromal invasion, not associated with other histotypes) of low-grade (LG-IDCs) and high-grade (HG-IDCs) was performed.

METHODS: The bibliographic research included multiple databases (PubMed, Scopus, Web of Science). Mild-moderate nuclear atypia favoured LG-IDCs, severe atypia favoured HG-IDCs.

RESULTS: Preoperative fine-needle aspiration cytology (FNAC) was performed in 13/94 published cases (14%): 10 parotid; two oral; one submandibular. All the cases were histologically LG-IDCs, except two parotid IDCs. FNAC results included: negative for malignancy (three of 13 cases, 23%); tumour of uncertain malignant potential (seven of 13, 54%); malignancy (three of 13, 23%). The ductal component was identified in two cases; mucoepidermoid carcinoma was suggested in two additional cases. The grade was underestimated on FNAC evaluation in one HG-IDC as focal high-grade features were present on subsequent histological examination. The cases diagnosed as malignant tumours or describing intermediate atypia resulted in LG-IDCs on subsequent histology. Occasional mitoses were described only in one HG-IDC; this feature may have not been considered in the remaining published cases.

CONCLUSIONS: FNAC and clinico-pathological correlation are important aids for clinicians and pathologists. FNAC could assist surgery even if an accurate diagnosis is sometimes impossible. Discrepancy in grading the nuclear atypia between the FNAC material and the resected specimen can occur, sometimes being unavoidable. Further studies are needed to better characterise this rare tumour.}, } @article {pmid31749200, year = {2020}, author = {Rousseau, S and Kritzman, L and Frenkel, TI and Levit-Binnun, N and Golland, Y}, title = {The association between mothers' and daughters' positive affect is moderated by child cardiac vagal regulation.}, journal = {Developmental psychobiology}, volume = {62}, number = {6}, pages = {804-815}, doi = {10.1002/dev.21939}, pmid = {31749200}, issn = {1098-2302}, support = {698/15//Israel Science Foundation/International ; }, mesh = {Adult ; Affect/*physiology ; Child ; Child Development/*physiology ; *Cooperative Behavior ; Female ; Humans ; *Mother-Child Relations ; Respiratory Sinus Arrhythmia/*physiology ; *Social Interaction ; *Socialization ; Vagus Nerve/physiology ; }, abstract = {INTRODUCTION: Extensive research has supported the importance of children's positive affect in fostering prosperous psychosocial adjustment. Children's positive affect is believed to be significantly shaped by their environment in general and their caregivers' positive affect in particular. The current study investigates the role of child cardiac vagal regulation, a psychophysiological marker for social engagement, in shaping the association between maternal positive affect and child positive affect.

METHODS: Mothers and daughters (ndyads  = 28) participated in two experimental conditions. In the non-interactive condition, they separately drew a picture without interacting. In the cooperative condition, they drew a picture together. We measured child respiratory sinus arrhythmia (RSA), a widely used indicator of cardiac vagal regulation, during both conditions. We also coded maternal and child positive affect during the cooperative condition.

RESULTS: Maternal positive affect was related to child positive affect, but only for children with medium-to-high tonic levels of RSA and RSA increases from non-interaction to interaction.

DISCUSSION: Results suggest that child RSA plays a significant role in positive emotion socialization, by making children more susceptible to the emotional cues of their caregivers. Hence, child RSA should be taken into account in preventive and therapeutic efforts regarding child positive affect socialization.}, } @article {pmid31748977, year = {2020}, author = {Petry, V and Bonadio, RC and Cagnacci, AQC and Senna, LAL and Campos, RDNG and Cotti, GC and Hoff, PM and Fragoso, MCBV and Estevez-Diz, MDP}, title = {Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).}, journal = {Familial cancer}, volume = {19}, number = {1}, pages = {47-53}, pmid = {31748977}, issn = {1573-7292}, mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/genetics/*radiotherapy ; Female ; Fibrosarcoma/epidemiology ; Follow-Up Studies ; *Genes, p53 ; *Germ-Line Mutation ; Humans ; Leiomyosarcoma/epidemiology ; Li-Fraumeni Syndrome/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Young Adult ; }, abstract = {The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.}, } @article {pmid31748491, year = {2019}, author = {Fujii, T and Ohno, N and Matsui, T and Sahara, N and Yoneyama, S and Inoue, H and Matsunaga, T}, title = {[A Case of Synchronous Diffuse Large B-Cell Lymphoma of the Right Breast and Invasive Ductal Carcinoma of the Left Breast].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {11}, pages = {1775-1778}, pmid = {31748491}, issn = {0385-0684}, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal ; *Carcinoma, Ductal, Breast ; Female ; Humans ; *Lymphoma, Large B-Cell, Diffuse ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; Neoplasms, Multiple Primary ; Positron Emission Tomography Computed Tomography ; }, abstract = {A woman in her early 60s noticed bilateral breast masses and visited a different hospital. Core needle biopsy showed diffuse large B-cell lymphoma of the right breast and invasive ductal carcinoma of the left breast. After referral to our department, PET-CT was performed. Compared with mild fluorodeoxyglucose accumulation in left breast cancer(BC), highly accumulated lesions were found on the right breast, left anterior chest wall, nasopharynx, and tonsil. The right breast lesion was the largest with a diameter of 30mm and was considered the primary lesion of malignant lymphoma(ML). The ML was classified as stage Ⅳ, pathologically proven with erythema of the left breast and nasopharynx. Three courses of R-CHOP were performed. However, due to suspicion of heart failure, chemotherapy was changed to R-CEOP(non-anthracycline-containing regimen)and 3 courses were additionally performed. The therapeutic effect of R-Chemo for ML was CR. Left BC showed a tendency of shrinkage. After intrathecal administration of anticancer drugs to prevent infiltration of ML into the central nervous system and preoperative endocrine therapy with aromatase inhibitor, left lumpectomy and sentinel lymph node biopsy were performed. BC was classified as clinical stage ⅠA and had an estrogen receptor score of 3b. Postoperative whole breast radiotherapy was completed, and the planned internal use of exemestane was more than 5 years. With multidisciplinary therapy, 3.5 years had passed since the initial treatment without recurrence.}, } @article {pmid31744918, year = {2019}, author = {Xie, M and Leroy, H and Mascarau, R and Woottum, M and Dupont, M and Ciccone, C and Schmitt, A and Raynaud-Messina, B and Vérollet, C and Bouchet, J and Bracq, L and Benichou, S}, title = {Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.}, journal = {mBio}, volume = {10}, number = {6}, pages = {}, pmid = {31744918}, issn = {2150-7511}, mesh = {CD4-Positive T-Lymphocytes/metabolism/virology ; Dendritic Cells/metabolism/virology ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Humans ; Macrophages/metabolism/virology ; Myeloid Cells/metabolism/virology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; *Viral Tropism ; *Virus Replication ; }, abstract = {Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.}, } @article {pmid31741805, year = {2019}, author = {Li, Y and Wei, Y and Tang, W and Luo, J and Wang, M and Lin, H and Guo, H and Ma, Y and Zhang, J and Li, Q}, title = {Association between the degree of fibrosis in fibrotic focus and the unfavorable clinicopathological prognostic features of breast cancer.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e8067}, pmid = {31741805}, issn = {2167-8359}, abstract = {OBJECTIVE: To explore the association between the degree of fibrosis in fibrotic focus (FF) and the unfavorable clinicopathological prognostic features of breast cancer.

METHODS: A total of 169 cases of breast invasive ductal carcinoma (IDC) were included in the study. Hematoxylin and eosin (H&E) staining was performed in the primary lesion of breast IDC and the degree of fibrosis in tumor-stromal FF was assessed. The association between the degree of fibrosis in FF and the well-known clinicopathologic features of breast cancer was investigated and the influence of the degree of fibrosis in FF on the survival was analyzed.

RESULTS: Tumor size >2 cm (P = 0.023), vascular invasion (P = 0.011), lymphatic vessel invasion (P < 0.001) and HER-2+ (P = 0.032) were positively correlated with the degree of fibrosis in FF in breast IDC. The result of multivariate analysis showed that lymphatic vessel invasion was the only independent correlation factor of high fibrosis in FF in breast IDC (OR = 3.82, 95% CI[1.13 ∼ 12.82], P = 0.031). The Nottingham prognostic index (NPI) of high fibrosis in FF was significantly higher than that of mild and moderate fibrosis in FF in the no vascular infiltration subgroup, the no nerve infiltration subgroup, and the Luminal A subgroup (P = 0.014, 0.039, and 0.018; respectively).

CONCLUSIONS: The high fibrosis in FF is closely associated with the strong invasiveness and the high malignancy of breast IDC. The degree of fibrosis in FF might be considered as a very practical and meaningful pathological feature of breast cancer.}, } @article {pmid31737920, year = {2020}, author = {Taylor, AS and Morgan, TM and Wallington, DG and Chinnaiyan, AM and Spratt, DE and Mehra, R}, title = {Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.}, journal = {The Prostate}, volume = {80}, number = {2}, pages = {146-152}, pmid = {31737920}, issn = {1097-0045}, support = {P50 CA069568/CA/NCI NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*genetics/*pathology ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal/*genetics/*pathology ; Cell Growth Processes/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/*pathology ; RNA, Neoplasm/*genetics ; }, abstract = {BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.

DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).

RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24).

CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.}, } @article {pmid31734782, year = {2020}, author = {Kim, K and Kim, IJ and Pak, K and Kim, SJ and Choi, SJ and Park, H and Kang, T and Kong, IJ and Shin, YB and Kim, H and Yoon, JA}, title = {The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {47}, number = {5}, pages = {1094-1102}, pmid = {31734782}, issn = {1619-7089}, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging/surgery ; Feasibility Studies ; Humans ; Lymph Node Excision ; *Lymphedema/diagnostic imaging/etiology ; Lymphoscintigraphy ; Mastectomy ; }, abstract = {PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy.

METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides.

RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm.

CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.}, } @article {pmid31734052, year = {2020}, author = {Chen, X and Yang, Y and Wang, W and Han, B and Qi, M and Geng, S and Xu, J and Zhang, Q and Wang, X and Chen, S and Shi, K and Ke, X and Zhang, J}, title = {Prognostic significance of the presence of intraductal carcinoma of the prostate and bone metastasis in needle biopsy for prostate carcinoma patients with Grade Group 5.}, journal = {Pathology, research and practice}, volume = {216}, number = {1}, pages = {152693}, doi = {10.1016/j.prp.2019.152693}, pmid = {31734052}, issn = {1618-0631}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplastic Processes ; Prognosis ; Prostate/pathology ; Prostatic Neoplasms/*diagnosis/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) and bone metastasis have been both identified to associate with unfavorable clinical outcome of the prostate carcinoma (PCa). Our objective is to examine whether IDC-P or bone metastasis at diagnostic biopsies was associated with each other and whether they were linked with overall survival (OS) and cancer specific survival (CSS) of Grade Group 5 patients. We retrospectively selected the prostate biopsy specimens of 120 PCa patients with Grade Group 5 from Qilu Hospital of Shandong University between 2012 and 2016. There were 12 patients with IDC-P only, 52 patients with bone metastasis only and 10 patients with both IDC-P and bone metastasis. Overall, there was a significant correlation between the presences of the IDC-P and bone metastasis (P = 0.003). Kaplan-Meier survival analysis demonstrated that the presence of IDC-P and bone metastasis in diagnostic needle biopsy both conferred unfavorable CSS of Grade Group 5 patients. In addition, the presence of bone metastasis was a poor predictor of OS. Univariate and multivariate analysis revealed that bone metastasis was an independent prognostic factor for OS of Grade Group 5 patients, but IDC-P failed to be significant for either OS or CSS. Collectively, our study suggested that bone metastasis is an important prognostic factor and superior than the presence of the IDC-P for PCa patients with Grade Group 5.}, } @article {pmid31732892, year = {2020}, author = {Ben-David, BM and Ben-Itzchak, E and Zukerman, G and Yahav, G and Icht, M}, title = {The Perception of Emotions in Spoken Language in Undergraduates with High Functioning Autism Spectrum Disorder: A Preserved Social Skill.}, journal = {Journal of autism and developmental disorders}, volume = {50}, number = {3}, pages = {741-756}, pmid = {31732892}, issn = {1573-3432}, mesh = {Adolescent ; Autism Spectrum Disorder/*psychology ; *Emotions ; Female ; Humans ; Language ; Male ; *Social Skills ; *Speech Perception ; Students ; Young Adult ; }, abstract = {Identifying emotions in speech is based on the interaction of lexical content and prosody. This may be disrupted in individuals with High-Functioning Autism Spectrum Disorder (HF-ASD). Undergraduates with HF-ASD (n = 20) and matched typically developed peers (n = 20) were tested using the (Hebrew) Test for Rating of Emotions in Speech. Participants rated the degree to which a target-emotion is present in spoken sentences, in which the emotional-lexical and -prosodic content appear in different combinations from trial to trial. No group differences were found in measures of emotion-identification, selective-attention (focusing on one target-channel) and integration. These preserved abilities can partially explain the high levels of independence and self-control characterizing students with HF-ASD. Support programs may rely on such skills to improve social interactions.}, } @article {pmid31721627, year = {2019}, author = {Mutar, MT and Goyani, MS and Had, AM and Mahmood, AS}, title = {Pattern of Presentation of Patients With Breast Cancer in Iraq in 2018: A Cross-Sectional Study.}, journal = {Journal of global oncology}, volume = {5}, number = {}, pages = {1-6}, pmid = {31721627}, issn = {2378-9506}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology ; Cross-Sectional Studies ; Female ; Humans ; Iraq ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Symptom Assessment ; }, abstract = {PURPOSE: This study aims to describe the pattern of presentation of Iraqi female patients with breast cancer by assessing the grades and stages of their cancers at the time of presentation, to identify patients' main complaints, and to discover whether there is any difference in presentation between patients in Iraq and those in other countries.

PATIENTS AND METHODS: This is a retrospective cross-sectional study that was performed in the National Center of Cancer in 2018. The target population was female patients with breast cancer who came to the Center for treatment and follow-up. A sample of 171 patients was drawn from this population. Self-evaluation forms were used in interviews with the patients to collect personal and sociodemographic data; clinical and histologic characteristics of the patients' tumors were obtained from their medical records. Ethical approval was obtained.

RESULTS: Forty-five percent of the patients were younger than age 50 years, and 25% were younger than age 45 years. In all, 42.9% of the patients were diagnosed with stage III and 25% with stage IV cancer, and metastasis was diagnosed in 24.1%. In our study population, 53.4% of the tumors were found in the right breast, and 3.9% of patients had bilateral breast tumors. The most common histopathologic type was invasive ductal carcinoma (81.4%) followed by invasive lobular carcinoma (6.9%) and tubular carcinoma (5.9%). The patients' most common complaints were breast lump (71.3%) and pain (18.9%). No correlation was found between tumor stage and breast self-examination, family history, education, occupation, histopathology, or grade.

CONCLUSION: Most of the patients are diagnosed at a late stage when treatment is less effective.}, } @article {pmid31719806, year = {2019}, author = {Mullins, BT and Gupta, G}, title = {Increased radiation toxicity with germline ATM variant of uncertain clinical significance.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {24}, number = {6}, pages = {672-680}, pmid = {31719806}, issn = {1507-1367}, abstract = {BACKGROUND: While patients with ataxia telangiectasia are known to have increased radiation sensitivity, patients with germline heterozygous ataxia telangiectasia mutated (ATM) mutations can have widely varying functional and clinical effects, which can make management decisions difficult. With an increased prevalence of gene panel-based testing for breast cancer patients, radiation oncologists are increasingly confronted with patients who carry germline ATM variants of uncertain clinical significance. This study describes the clinical courses and outcomes of 5 breast cancer patients with varying germline heterozygous ATM mutations undergoing radiation therapy at our institution in order to provide additional knowledge of the varying clinical effects to aid future decision making.

CASE SERIES: We identified 5 patients with breast cancer and varying germline heterozygous ATM mutations treated at the University of North Carolina Hospitals between 2015 and 2017. The median age at breast cancer diagnosis for the patient series was 46. Clinical effects of radiation treatment varied amongst the 5 patients. The one patient with a pathogenic ATM mutation had no increased radiation related toxicity. Of the 4 patients with ATM variants of uncertain significance, one patient had increased radiation sensitivity with Grade 3 dermatitis. All patients have remained recurrence free with a median duration of 18 months.

CONCLUSION: Our data illustrates that patients with germline heterozygous ATM mutations can have widely varying clinical effects with radiation therapy. Given the possibility of unpredictable deleterious effects, our study highlights the importance of caution and careful consideration when devising the multi-modality management strategy in these patients.}, } @article {pmid31711023, year = {2019}, author = {Zhou, J and Tan, H and Bai, Y and Li, J and Lu, Q and Chen, R and Zhang, M and Feng, Q and Wang, M}, title = {Evaluating the HER-2 status of breast cancer using mammography radiomics features.}, journal = {European journal of radiology}, volume = {121}, number = {}, pages = {108718}, doi = {10.1016/j.ejrad.2019.108718}, pmid = {31711023}, issn = {1872-7727}, mesh = {Area Under Curve ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/*genetics ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics ; China ; Female ; Genes, erbB-2/*genetics ; Humans ; Mammography/*methods ; Middle Aged ; Preoperative Care ; ROC Curve ; Sensitivity and Specificity ; Support Vector Machine ; }, abstract = {PURPOSE: The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features.

METHODS: A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n = 244) and a testing set (n = 62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models.

RESULTS: Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively.

CONCLUSIONS: Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.}, } @article {pmid31710002, year = {2020}, author = {Zhu, S and Zhao, JG and Chen, JR and Liu, ZH and Sun, GX and Wang, ZP and Ni, YC and Dai, JD and Shen, PF and Zeng, H}, title = {Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {5}, pages = {519-525}, pmid = {31710002}, issn = {1745-7262}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/*pathology/surgery ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Nomograms ; Prognosis ; Proportional Hazards Models ; Prostate/pathology ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Risk Factors ; Seminal Vesicles/pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive pathological pattern of prostate cancer (PCa). We investigated the association of IDC-P in prostate biopsy (PBx) with several pathological features after radical prostatectomy (RP) and its prognostic value in high-risk PCa. A total of 418 patients with high-risk PCa after RP were included in this study. IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification. Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features. Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P. IDC-P was identified in PBx in 36/418 (8.6%) patients. Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP, including Gleason score 8-10 (P < 0.001), seminal vesicular invasion (P < 0.001), and pathological T (pT) 3a (P = 0.043). Patients with IDC-P in PBx manifested poorer biochemical-free survival (BFS) than those without IDC-P (37.47 months vs not reached, P < 0.001). The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools. We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa. In addition, IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.}, } @article {pmid31706703, year = {2019}, author = {Quagliarini, F and Mir, AA and Balazs, K and Wierer, M and Dyar, KA and Jouffe, C and Makris, K and Hawe, J and Heinig, M and Filipp, FV and Barish, GD and Uhlenhaut, NH}, title = {Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.}, journal = {Molecular cell}, volume = {76}, number = {4}, pages = {531-545.e5}, pmid = {31706703}, issn = {1097-4164}, support = {K99 CA154887/CA/NCI NIH HHS/United States ; R00 CA154887/CA/NCI NIH HHS/United States ; R01 DK108987/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Blood Glucose/metabolism ; Chromatin/*metabolism ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; *Diet, High-Fat ; Dietary Fats/administration & dosage/blood/*metabolism ; Disease Models, Animal ; *Energy Metabolism/genetics ; Fasting/metabolism ; Gene Expression Regulation ; Glucocorticoids/metabolism ; Gluconeogenesis ; Ligands ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/blood/genetics/*metabolism ; PPAR alpha/genetics/metabolism ; Postprandial Period ; Receptors, Glucocorticoid/deficiency/genetics/*metabolism ; STAT5 Transcription Factor/genetics/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Triglycerides/blood ; }, abstract = {The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.}, } @article {pmid31700920, year = {2019}, author = {Chen, H and Bai, F and Wang, M and Zhang, M and Zhang, P and Wu, K}, title = {The prognostic significance of co-existence ductal carcinoma in situ in invasive ductal breast cancer: a large population-based study and a matched case-control analysis.}, journal = {Annals of translational medicine}, volume = {7}, number = {18}, pages = {484}, pmid = {31700920}, issn = {2305-5839}, abstract = {BACKGROUND: To evaluate the prognostic significance of co-existence ductal carcinoma in situ (DCIS) in invasive ductal breast cancer (IDC) compared with pure IDC.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify unilateral IDC cases between 2004 and 2015, which were grouped into pure IDC and IDC with DCIS component (IDC-DCIS). Comparisons of the distribution of clinical-pathological characteristics the two groups were performed using Pearson's chi-square. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared across RS groups using the log-rank statistic. Cox models were fitted to assess the factors independently associated with survival. A 1:1 matched case-control analysis was conducted with each clinical-pathological characteristic matched completely.

RESULTS: A total of 98,097 pure IDC cases (39.6%) and 149,477 IDC-DCIS cases (60.4%) were enrolled. IDC-DCIS patients were presented with less aggressive characteristics such as lower proportion of histologic grade III (34.2% vs. 42.2%, P<0.001), ER negative (16.8% vs. 26.1%, P<0.001) and PR negative (26.5% vs. 35.7%, P<0.001) disease and higher proportion of T1 cases (68.7% vs. 58.2%, P<0.001) compared with pure IDC patients. Co-existence DCIS was an independent prognostic factor for BCSS and OS in the whole cohort. According to the multivariate analysis, it was an independent favorable prognostic factor among ER positive cases, but an independent negative prognostic factor among ER negative cases based on the matched cohort.

CONCLUSIONS: Co-existence DCIS showed quite different prognostic significance among ER positive and negative disease.}, } @article {pmid31699638, year = {2020}, author = {Lamb, LR and Lehman, CD and Oseni, TO and Bahl, M}, title = {Ductal Carcinoma In Situ (DCIS) at Breast MRI: Predictors of Upgrade to Invasive Carcinoma.}, journal = {Academic radiology}, volume = {27}, number = {10}, pages = {1394-1399}, doi = {10.1016/j.acra.2019.09.025}, pmid = {31699638}, issn = {1878-4046}, mesh = {Adult ; Aged ; Breast ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma in Situ ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: To determine the upgrade rate of magnetic resonance imaging (MRI)-detected ductal carcinoma in situ (DCIS) and to identify patient, imaging, and pathologic features that may predict the risk of upgrade.

MATERIALS AND METHODS: Medical chart review from January 2007 to December 2016 identified 60 patients with 61 cases of MRI-detected DCIS and negative mammographic evaluations within 1 year prior to the MRI. Imaging and pathology reports were reviewed. Standard statistical tests, including Student's t-tests and chi-square tests, were used to compare patient, imaging, and pathologic features between the cases of DCIS that did and did not upgrade to invasive carcinoma at surgery.

RESULTS: Over a 10-year period, 60 patients (mean age 52 years, range 30-76 years) were diagnosed with 61 cases of MRI-detected DCIS. Two-thirds of DCIS cases were detected on MRI examinations that were performed for purposes of high-risk screening (67.2%, 41/61). MRI features that led to the DCIS diagnosis were nonmass enhancement in 78.7% (48/61), enhancing mass in 16.4% (10/61), nonmass enhancement and enhancing mass in 3.3% (2/61), and enhancing focus in 1.6% (1/61). Thirteen cases (21.3%, 13/61) were upgraded to invasive ductal carcinoma at surgery. DCIS cases that upgraded were larger on MRI (40 mm vs 17 mm, p < 0.01) and more likely to be associated with comedonecrosis at biopsy (38.5% [5/13] vs 6.3% [3/48], p < 0.01).

CONCLUSION: The upgrade rate of MRI-detected DCIS to invasive ductal carcinoma at surgery is 21.3%. Features that are associated with upgrade include large size on MRI and the presence of comedonecrosis at biopsy.}, } @article {pmid31697865, year = {2020}, author = {Palicelli, A}, title = {Intraductal carcinomas of the salivary glands: systematic review and classification of 93 published cases.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {128}, number = {3}, pages = {191-200}, doi = {10.1111/apm.13009}, pmid = {31697865}, issn = {1600-0463}, mesh = {Biomarkers, Tumor/metabolism ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Humans ; Neoplasm Recurrence, Local/metabolism/pathology ; Salivary Gland Neoplasms/metabolism/*pathology ; Salivary Glands/metabolism/pathology ; }, abstract = {Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade (LG-IDCs) or high-grade (HG-IDCs) was performed: IDCs were classified using the apocrine (AR+/S100-) vs intercalated (S100+/AR-) classification. Eighty-two LG-IDCs and 11 HG-IDCs were identified (84% parotid; 11% oral; 3% submandibular; 1% lacrimal; and 1% unknown). Out of 11 HG-IDCs, 2 HG-IDCs (18%) recurred as HG-IDC or invasive carcinoma. IDCs were classified as follows: intercalated (30%); mixed apocrine and intercalated (27%); apocrine (11%); oncocytic (6%); intercalated with focal oncocytic features (1%); and unclassifiable (25%). Double AR/S100 expressors (4%) or discrepancies between morphology and immunophenotype (9%) were found. Apocrine features and necrosis were more frequent in HG-IDCs (55%; 45%). Pleomorphism favored HG-IDCs (especially when combined with >10 mitoses/10 HPFs and/or Ki67 index >10%), being associated with apocrine areas at least in 3 HG-IDCs (27%). IDCs were typically mammaglobin+/ER-/PR-/DOG1-. No immunomarker clearly distinguished HG-IDCs from LG-IDCs. About 57% IDCs (16 LG-IDCs, 1 HG-IDC) showed RET rearrangements, including NCOA4-RET (eight intercalated and two unclassifiable IDCs) and TRIM27-RET fusions (two mixed IDCs). No ETV6, ALK-1, ROS, NTRK3, MAML2, MAML3, or PLAG1 rearrangements were identified. Complete excision and total sampling should exclude invasive areas.}, } @article {pmid31690273, year = {2019}, author = {Surov, A and Chang, YW and Li, L and Martincich, L and Partridge, SC and Kim, JY and Wienke, A}, title = {Apparent diffusion coefficient cannot predict molecular subtype and lymph node metastases in invasive breast cancer: a multicenter analysis.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1043}, pmid = {31690273}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal/*diagnosis/pathology ; Diagnostic Imaging ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Lymph Nodes/*diagnostic imaging/pathology ; Lymphatic Metastasis ; Mammary Glands, Human/*diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Phenotype ; Prognosis ; }, abstract = {BACKGROUND: Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC.

METHODS: Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann-Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman's rank correlation coefficient.

RESULTS: ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = - 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67.

CONCLUSION: ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.}, } @article {pmid31689410, year = {2020}, author = {Scheideler, M and Vidakovic, I and Prassl, R}, title = {Lipid nanocarriers for microRNA delivery.}, journal = {Chemistry and physics of lipids}, volume = {226}, number = {}, pages = {104837}, doi = {10.1016/j.chemphyslip.2019.104837}, pmid = {31689410}, issn = {1873-2941}, mesh = {Animals ; Drug Carriers/chemistry ; *Drug Delivery Systems ; Humans ; Lipids/*chemistry ; MicroRNAs/*chemistry ; Nanoparticles/*chemistry ; }, abstract = {Non-coding RNAs (ncRNAs) like microRNAs (miRNAs) or small interference RNAs (siRNAs) with their power to selectively silence any gene of interest enable the targeting of so far 'undruggable' proteins and diseases. Such RNA molecules have gained much attention from biotech and pharmaceutical companies, which led to the first Food and Drug Administration (FDA) approved ncRNA therapeutic in 2018. However, the main barrier in clinical practice of ncRNAs is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver them to specific tissues and cell types, and release them into the cytoplasm of the targeted cells, all without inducing adverse effects. For that reason, drug delivery approaches, formulations, technologies and systems for transporting pharmacological ncRNA compounds to achieve a diagnostic or therapeutic effect in the human body are in demand. Here, we review the development of therapeutic lipid-based nanoparticles for delivery of miRNAs, one class of endogenous ncRNAs with specific regulatory functions. We outline challenges and opportunities for advanced miRNA-based therapies, and discuss the complexity associated with the delivery of functional miRNAs. Novel strategies are addressed how to deal with the most critical points in miRNA delivery, such as toxicity, specific targeting of disease sites, proper cellular uptake and endosomal escape of miRNAs. Current fields of application and various preclinical settings involving miRNA therapeutics are discussed, providing an outlook to future clinical approaches. Following the current trends and technological developments in nanomedicine exciting new delivery systems for ncRNA-based therapeutics can be expected in upcoming years.}, } @article {pmid31686242, year = {2019}, author = {Harada-Shoji, N and Soga, T and Tada, H and Miyashita, M and Harada, M and Watanabe, G and Hamanaka, Y and Sato, A and Suzuki, T and Suzuki, A and Ishida, T}, title = {A metabolic profile of routine needle biopsies identified tumor type specific metabolic signatures for breast cancer stratification: a pilot study.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {15}, number = {11}, pages = {147}, pmid = {31686242}, issn = {1573-3890}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/diagnosis/*metabolism ; Female ; Humans ; *Metabolomics ; Middle Aged ; Pilot Projects ; }, abstract = {INTRODUCTION: Metabolomics has recently emerged as a tool for understanding comprehensive tumor-associated metabolic dysregulation. However, only limited application of this technology has been introduced into the clinical setting of breast cancer.

OBJECTIVES: The aim of this study was to determine the feasibility of metabolome analysis using routine CNB/VAB samples from breast cancer patients and to elucidate metabolic signatures using metabolic profiling.

METHODS: After breast cancer screenings, 20 consecutive patients underwent CNB/VAB, and diagnosed with benign, DCIS and IDC by histology. Metabolome analysis was performed using CE-MS. Differential metabolites were then analyzed and evaluated with MetaboAnalyst 4.0.

RESULTS: We measured 116-targeted metabolites involved in energy metabolism. Principal component analysis and unsupervised hierarchical analysis revealed a distinct metabolic signature unique to namely "pure" IDC samples, whereas that of DCIS was similar to benign samples. Pathway analysis unveiled the most affected pathways of the "pure" IDC metabotype, including "pyrimidine," "alanine, aspartate, and glutamate" and "arginine and proline" pathways.

CONCLUSIONS: Our proof-of-concept study demonstrated that CE-MS-based CNB/VAB metabolome analysis is feasible for implementation in routine clinical settings. The most affected pathways in this study may contribute to improved breast cancer stratification and precision medicine.}, } @article {pmid31685259, year = {2020}, author = {Liu, C and Dingee, CK and Warburton, R and Pao, JS and Kuusk, U and Bazzarelli, A and Sidhu, R and McKevitt, EC}, title = {Pure flat epithelial atypia identified on core needle biopsy does not require excision.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {46}, number = {2}, pages = {235-239}, doi = {10.1016/j.ejso.2019.10.029}, pmid = {31685259}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Female ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: Routine excision of flat epithelial atypia (FEA) of the breast found on core needle biopsy (CNB) is being questioned and a policy of selective excision of FEA was adopted in our area. The purpose of this study was to evaluate the upstage rate to malignancy across multiple diagnostic centers in our area following the policy of selective excision and to identify factors predictive of malignancy.

METHODS: Patients having excision of CNB FEA at our regional Hospital between 2013 and 2017 were identified. The primary endpoint was upstage to malignancy after excision. We also assessed for clinical, radiological, and pathological features associated with malignancy.

RESULTS: We identified 187 patients. Eighty-nine had pure FEA, 71 had concurrent ADH, and 18 had other pathological lesions. Following surgical excision, 9 patients were upstaged to malignancy (4. 8%) with 8 having concurrent ADH (2 invasive ductal carcinoma, 6 DCIS) and 1 with concurrent Complex Sclerosing Lesion (DCIS). None of the pure FEA cases upstaged. The presence of ADH or CSL in the CNB were the only factors found to be predictive of upstaging (p = 0.001, p = 0.0001 respectively).

CONCLUSIONS: The upstage rate to malignancy after excision of pure FEA at out center is 0%. Therefore, we recommend that pure FEA with radiology and pathology concordance does not require surgical excision and can instead be followed with serial imaging. However, patients with FEA in association with other high-risk lesions should be managed as per indicated for the other high-risk lesion and FEA with ADH should be excised.}, } @article {pmid31680568, year = {2019}, author = {Izumo, W and Higuchi, R and Furukawa, T and Yazawa, T and Uemura, S and Matsunaga, Y and Shiihara, M and Yamamoto, M}, title = {Comparison of patients with invasive intraductal papillary mucinous carcinoma and invasive ductal carcinoma of the pancreas: a pathological type- and stage-matched analysis.}, journal = {Scandinavian journal of gastroenterology}, volume = {54}, number = {11}, pages = {1412-1418}, doi = {10.1080/00365521.2019.1684554}, pmid = {31680568}, issn = {1502-7708}, mesh = {Adenocarcinoma/*pathology/surgery ; Adenocarcinoma, Mucinous/*pathology/surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology/surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatectomy ; Pancreatic Neoplasms/*pathology/surgery ; Retrospective Studies ; }, abstract = {Objective: We compared the pathological features and stage-matched outcomes of patients with invasive intraductal papillary mucinous carcinoma (IPMC) and invasive ductal carcinoma (IDC) of the pancreas to identify the reasons for these diseases' differing prognoses.Methods: We analyzed 114 and 560 patients who underwent curative pancreatectomy for invasive IPMC and IDC, respectively, and analyzed their clinicopathological factors.Results: The disease-specific survival (DSS) of patients with invasive IPMC was significantly superior to that of patients with IDC exhibiting all pathological types at all stages. The DSS of patients with invasive IPMC exhibiting tubular adenocarcinoma was significantly superior to that of their counterparts with IDC only among those with stage IIB (p = .045). When comparing patients with stage IIB tubular adenocarcinoma-type invasive IPMC to their counterparts with IDC, the tumor size (2.6 cm vs. 3.3 cm, p = .010), serum level of carbohydrate antigen 19-9 (253 vs. 474 U/mL, p = .035), number of metastatic lymph nodes (3.1 vs. 4.5, p = .033), vascular invasion rate (14% vs. 41%, p = .0019) and local invasion rate (79% vs. 95%, p = .0045) were lower in the former group. Moreover, the frequency of pathological tubular adenocarcinoma grade 1 was higher in patients with invasive IPMC than in those with IDC (38% vs. 12%, p = .0004) as was the R0 resection rate (90% vs. 65%, p = .0027).Conclusions: In pathological type- and stage-matched analyses, invasive IPMC was associated with a better prognosis than IDC only in patients with stage IIB, as factors governing tumor aggressiveness were milder in the former group than in the latter.}, } @article {pmid31677352, year = {2020}, author = {Chen, HH and Chen, DY and Huang, LG and Chen, YM and Hsieh, CW and Hung, WT and Tang, KT and Chen, G}, title = {Association between periodontitis and the risk of inadequate disease control in patients with rheumatoid arthritis under biological treatment.}, journal = {Journal of clinical periodontology}, volume = {47}, number = {2}, pages = {148-159}, doi = {10.1111/jcpe.13213}, pmid = {31677352}, issn = {1600-051X}, mesh = {Arthritis, Rheumatoid/*complications/*drug therapy/*epidemiology ; Humans ; Periodontitis/*complications/*epidemiology/*therapy ; Prospective Studies ; }, abstract = {AIM: To assess the association between periodontitis (PD) and inadequate disease control (IDC) in patients with rheumatoid arthritis (RA) receiving biological therapy.

MATERIALS AND METHODS: In total, 111 RA patients receiving biological therapy for at least 3 months were assessed for periodontal disease at baseline. RA disease activity was assessed at baseline and at 3 months of follow-up. A multivariable logistic regression analysis was used to estimate the association between PD and IDC, adjusting for age, sex, smoking, diabetes, and baseline RA disease activity. An additional exploratory model further controlled for disease characteristics and other medications.

RESULTS: Among 111 patients, 84 (75.7%) had PD, of whom 37 (44.0%) received periodontal treatment. Thirty-four (40.5%) of PD patients had IDC; 12 (32.4%) of treated PD patients and 22 (46.8%) of untreated patients had IDC, respectively. The ORs (95% CIs) for IDC were 1.45 (0.50-4.23) in PD patients and 1.84 (0.59-5.76) in untreated PD patients. In the exploratory model, the ORs (95% CIs) for IDC were 5.00 (1.19-21.03) in PD patients and 6.26 (1.34-29.34) in untreated PD patients.

CONCLUSION: This single-centre, prospective study failed to demonstrate a consistently positive correlation between PD and IDC in RA patients receiving biological treatment.}, } @article {pmid31673038, year = {2019}, author = {Golberg, A and Sheviryov, J and Solomon, O and Anavy, L and Yakhini, Z}, title = {Molecular harvesting with electroporation for tissue profiling.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {15750}, pmid = {31673038}, issn = {2045-2322}, mesh = {Animals ; Electroporation/*methods ; Female ; Gene Ontology ; Genomics ; Hep G2 Cells ; Humans ; Kidney/*metabolism/pathology ; Liver/*metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/metabolism/pathology ; Proteomics ; RNA, Neoplasm/metabolism ; Transplantation, Heterologous ; }, abstract = {Recent developments in personalized medicine are based on molecular measurement steps that guide personally adjusted medical decisions. A central approach to molecular profiling consists of measuring DNA, RNA, and/or proteins in tissue samples, most notably in and around tumors. This measurement yields molecular biomarkers that are potentially predictive of response and of tumor type. Current methods in cancer therapy mostly use tissue biopsy as the starting point of molecular profiling. Tissue biopsies involve a physical resection of a small tissue sample, leading to localized tissue injury, bleeding, inflammation and stress, as well as to an increased risk of metastasis. Here we developed a technology for harvesting biomolecules from tissues using electroporation. We show that tissue electroporation, achieved using a combination of high-voltage short pulses, 50 pulses 500 V cm[-1], 30 µs, 1 Hz, with low-voltage long pulses 50 pulses 50 V cm[-1], 10 ms, delivered at 1 Hz, allows for tissue-specific extraction of RNA and proteins. We specifically tested RNA and protein extraction from excised kidney and liver samples and from excised HepG2 tumors in mice. Further in vivo development of extraction methods based on electroporation can drive novel approaches to the molecular profiling of tumors and of tumor environment and to related diagnosis practices.}, } @article {pmid31672492, year = {2020}, author = {Kim, JE and Kim, BG and Jang, Y and Kang, S and Lee, JH and Cho, NH}, title = {The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer.}, journal = {Cancer letters}, volume = {469}, number = {}, pages = {256-265}, doi = {10.1016/j.canlet.2019.10.039}, pmid = {31672492}, issn = {1872-7980}, mesh = {Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/drug effects/genetics ; Disease Progression ; Exosome Multienzyme Ribonuclease Complex/genetics ; Exosomes/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*genetics ; Proto-Oncogene Proteins c-fos/*genetics ; Stromal Cells/metabolism/pathology ; Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology ; }, abstract = {Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.}, } @article {pmid31666416, year = {2019}, author = {Autenshlyus, AI and Davletova, KI and Studenikina, AA and Mikhaylova, ES and Varaksin, NA and Zhurakovsky, IP and Proskura, AV and Sidorov, SV and Lyakhovich, VV}, title = {[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].}, journal = {Biomeditsinskaia khimiia}, volume = {65}, number = {5}, pages = {424-431}, doi = {10.18097/PBMC20196505424}, pmid = {31666416}, issn = {2310-6972}, mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal/*immunology ; Cytokines/*immunology ; *Extracellular Matrix ; Female ; Humans ; Lymphatic Metastasis ; *Tumor Microenvironment ; }, abstract = {The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.}, } @article {pmid31665413, year = {2019}, author = {Mi, Y and Lv, P and Wang, F and Li, L and Zhu, M and Cao, Q and Liu, J and Dong, M and Shi, Y and Fan, R}, title = {Efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy in breast-conserving surgery for early-stage breast cancer: a single-centre study in China.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {12}, pages = {1120-1125}, doi = {10.1093/jjco/hyz128}, pmid = {31665413}, issn = {1465-3621}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology/radiation effects/surgery ; Breast Neoplasms/pathology/*radiotherapy/*surgery ; China ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Radiotherapy Dosage ; Radiotherapy, Adjuvant/adverse effects ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: The purpose of this study was to evaluate the efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy for the treatment of Chinese patients with early-stage breast cancer.

METHODS: Between September 2014 and May 2017, breast cancer patients undergoing targeted intraoperative radiotherapy at our facility were retrospectively recruited for this study. Intraoperative radiotherapy was performed with a 50-kV X-ray source in an Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany). The one-time prescribed irradiation dose to the tumour bed was 20 Gy. Recurrence, death, late complications, and cosmetic outcomes were recorded. Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group.

RESULTS: A total of 77 patients who were treated with targeted intraoperative radiotherapy only were recruited. The cohort had a mean age of 58 years; patients with T1, N0, and invasive ductal carcinoma accounted for 75.3, 89.6, and 84.4%, respectively; the median follow-up duration was 40 months; there were 2 patients of recurrence and 2 patients of death. There were no patients of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above. The main complications were breast oedema (18.2%), seroma (15.6%), chromatosis (9.1%), induration (7.8%), pain (5.2%), skin depression (2.6%), mild dry cough (2.6%), delayed wound healing (1.3%), and wound infection (1.3%). Seventy-three patients participated in the cosmetic outcome evaluation, which yielded an excellent or good rate of 95.9%.

CONCLUSIONS: Due to its low recurrence rates, lack of high-grade late radiotoxicity, and excellent cosmetic outcomes, targeted intraoperative radiotherapy may be a suitable treatment for select early-stage breast cancer patients in China.}, } @article {pmid31663391, year = {2020}, author = {Oron, Y and Levy, O and Avivi-Reich, M and Goldfarb, A and Handzel, O and Shakuf, V and Ben-David, BM}, title = {Tinnitus affects the relative roles of semantics and prosody in the perception of emotions in spoken language.}, journal = {International journal of audiology}, volume = {59}, number = {3}, pages = {195-207}, doi = {10.1080/14992027.2019.1677952}, pmid = {31663391}, issn = {1708-8186}, mesh = {Adult ; Attention ; Comprehension ; Cues ; *Emotions ; Female ; Humans ; Language ; Male ; Middle Aged ; *Semantics ; Speech ; *Speech Perception ; Task Performance and Analysis ; Tinnitus/*psychology ; }, abstract = {Objective: Understanding communication difficulties related to tinnitus, by identifying tinnitus-related differences in the perception of spoken emotions, focussing on the roles of semantics (words), prosody (tone of speech) and their interaction.Study sample and design: Twenty-two people-with-tinnitus (PwT) and 24 people-without-tinnitus (PnT) listened to spoken sentences made of different combinations of four discrete emotions (anger, happiness, sadness, neutral) presented in the prosody and semantics (Test for Rating Emotions in Speech). In separate blocks, listeners were asked to attend to the sentence as a whole, integrating both speech channels (gauging integration), or to focus on one channel only (gauging identification and selective attention). Their task was to rate how much they agree the sentence conveys each of the predefined emotions.Results: Both groups identified emotions similarly, and performed with similar failures of selective attention. Group differences were found in the integration of channels. PnT showed a bias towards prosody, whereas PwT weighed both channels equally.Conclusions: Tinnitus appears to impact the integration of the prosodic and semantic channels. Three possible sources are suggested: (a) sensory: tinnitus may reduce prosodic cues. (b) Cognitive: tinnitus-related reduction in cognitive processing.}, } @article {pmid31662082, year = {2019}, author = {Bastian, B and Vauclair, CM and Loughnan, S and Bain, P and Ashokkumar, A and Becker, M and Bilewicz, M and Collier-Baker, E and Crespo, C and Eastwick, PW and Fischer, R and Friese, M and Gómez, Á and Guerra, VM and Guevara, JLC and Hanke, K and Hooper, N and Huang, LL and Junqi, S and Karasawa, M and Kuppens, P and Leknes, S and Peker, M and Pelay, C and Pina, A and Sachkova, M and Saguy, T and Silfver-Kuhalampi, M and Sortheix, F and Tong, J and Yeung, VW and Duffy, J and Swann, WB}, title = {Explaining illness with evil: pathogen prevalence fosters moral vitalism.}, journal = {Proceedings. Biological sciences}, volume = {286}, number = {1914}, pages = {20191576}, pmid = {31662082}, issn = {1471-2954}, mesh = {Biological Evolution ; *Communicable Diseases ; Humans ; *Morals ; Prevalence ; Religion ; *Vitalism ; }, abstract = {Pathogens represent a significant threat to human health leading to the emergence of strategies designed to help manage their negative impact. We examined how spiritual beliefs developed to explain and predict the devastating effects of pathogens and spread of infectious disease. Analysis of existing data in studies 1 and 2 suggests that moral vitalism (beliefs about spiritual forces of evil) is higher in geographical regions characterized by historical higher levels of pathogens. Furthermore, drawing on a sample of 3140 participants from 28 countries in study 3, we found that historical higher levels of pathogens were associated with stronger endorsement of moral vitalistic beliefs. Furthermore, endorsement of moral vitalistic beliefs statistically mediated the previously reported relationship between pathogen prevalence and conservative ideologies, suggesting these beliefs reinforce behavioural strategies which function to prevent infection. We conclude that moral vitalism may be adaptive: by emphasizing concerns over contagion, it provided an explanatory model that enabled human groups to reduce rates of contagious disease.}, } @article {pmid31661032, year = {2019}, author = {Klomek, AB}, title = {Prevention of postpartum suicidality in Israel.}, journal = {Israel journal of health policy research}, volume = {8}, number = {1}, pages = {77}, pmid = {31661032}, issn = {2045-4015}, mesh = {Child ; Female ; Humans ; Israel ; Postpartum Period ; Pregnancy ; Risk Factors ; *Suicide ; USSR ; }, abstract = {Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic-not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.}, } @article {pmid31660917, year = {2019}, author = {Peng, Z and Klomek, AB and Li, L and Su, X and Sillanmäki, L and Chudal, R and Sourander, A}, title = {Associations between Chinese adolescents subjected to traditional and cyber bullying and suicidal ideation, self-harm and suicide attempts.}, journal = {BMC psychiatry}, volume = {19}, number = {1}, pages = {324}, pmid = {31660917}, issn = {1471-244X}, mesh = {Adolescent ; Adolescent Behavior ; Bullying/*statistics & numerical data ; Child ; China/epidemiology ; Crime Victims/*statistics & numerical data ; Cyberbullying/statistics & numerical data ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Self-Injurious Behavior/*epidemiology/etiology ; Students/statistics & numerical data ; *Suicidal Ideation ; Suicide, Attempted/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The incidence of bullying is high among adolescents. Adolescents who were victims of bullying have a higher risk of self-harm and suicidal behavior than adolescents who were non-victims. However, research on suicide and both traditional and cyber bullying was limited in China. Therefore, this study examined the associations between Chinese adolescents who were the victims of traditional and cyber bullying and the prevalence of suicidal ideation, self-harm and suicide attempts.

METHODS: This was a population-based study of 2647 students (51.2% girls) with a mean age of 13.6 ± 1.1 years from 10 junior high schools in Shantou, China. Information on bullying victimization, suicidal ideation, self-harm and suicide attempts were collected using a self-administered questionnaire and the psychopathology of the students was assessed using the Strengths and Difficulties Questionnaire (SDQ). The associations were examined with multinomial logistic regression, adjusted for covariates.

RESULTS: Traditional bullying victimization was reported by 16.7% of the adolescents, cyber bullying victimization by 9.0% and both by 3.5%. The prevalence of suicidal ideation was 23.5%, self-harm was 6.2% and suicide attempts was 4.2%. Psychopathology symptoms were risk factors for suicide ideation only, ideation plus self-harm, self-harm only and suicide attempts. Victims of both traditional and cyber bullying had the highest risk of suicidal ideation only, ideation plus self-harm and suicide attempts, compared to those reporting one form of bullying. Victims of cyber bullying only had the second highest risk of suicidal ideation only and suicidal ideation plus self-harm compared to non-victims.

CONCLUSIONS: Adolescents who were victims of both traditional and cyber bullying had greater risks of adverse outcomes of suicidal ideation only, suicidal ideation plus self-harm and suicide attempts. The results of the current study suggest that those exposed to both forms of bullying should be routinely screened for suicidal risk. In addition, school-based anti-bully interventions should also target cyber bullying.}, } @article {pmid31656498, year = {2019}, author = {Mohammedi, L and Doula, FD and Mesli, F and Senhadji, R}, title = {Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.}, journal = {African health sciences}, volume = {19}, number = {2}, pages = {2140-2146}, pmid = {31656498}, issn = {1729-0503}, mesh = {Adult ; Aged ; Algeria ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cyclin D1/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas.

OBJECTIVES: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters.

MATERIALS AND METHODS: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138).

RESULTS: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression.

CONCLUSION: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.}, } @article {pmid31653162, year = {2019}, author = {Khater, AI and Noaman, MK and Abdel Hafiz, MN and Moneer, MM and Elattar, IA}, title = {Health-Related Quality of Life among Egyptian Female Breast Cancer Patients at the National Cancer Institute, Cairo University.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {10}, pages = {3113-3119}, pmid = {31653162}, issn = {2476-762X}, mesh = {Breast Neoplasms/epidemiology/pathology/*therapy ; Cancer Care Facilities/*organization & administration ; Combined Modality Therapy ; Cross-Sectional Studies ; Egypt/epidemiology ; Female ; Follow-Up Studies ; Health Status ; Humans ; Middle Aged ; Prognosis ; *Quality of Life ; Surveys and Questionnaires ; Universities ; }, abstract = {BACKGROUND: To measure the quality of life (QoL) of Egyptian females with breast cancer (BC) at the National Cancer Institute (NCI), Cairo University (CU) and its relations with the socio-demographic and clinical characteristics.

METHODS: A total of 200 female BC patients were recruited from the medical oncology outpatient clinic during a period from December 2015 to March 2018. The instrument of this study consisted of two parts: the first for Socio-demographic and clinicopathological characteristics, and the second was the Functional Assessment of Cancer Therapy-Breast for patients with Lymphedema (FACT-B+4) questionnaire.

RESULTS: The majority of the study participants were married, housewives, and without a family history of cancer (70.0%, 93.0%, and 63.0%, respectively). Most of them presented with breast mass, had IDC, grade II and disease stage III at diagnosis (89.0%, 84.5%, 85.6% and 56.8%, respectively) and had undergone modified radical mastectomy, received adjuvant chemotherapy, radiation, and hormonal therapy (62.0%, 83.8%, 73.5% and 60.5%, respectively). The median FACT-B score was 81 (range 35-133). The medians of subscales were: physical well-being 13 (range 0-28), social well-being 20 (range 0-28), emotional well-being 15 (range 2-24), and functional well-being 16 (range 2-28). The median score for breast subscale was 19 (range 2-32). Many factors affected the QoL scores, including age, marital status, occupation, smoking, residence, comorbidities, symptoms, grade, chemotherapy, radiation, and recurrence.

CONCLUSION: QoL of Egyptian females with BC was influenced by several factors like age, marital status, occupation, smoking, residence, comorbidities, symptoms, grade, chemotherapy, radiation, and recurrence.}, } @article {pmid31650283, year = {2020}, author = {Dekel, S and Ein-Dor, T and Dishy, GA and Mayopoulos, PA}, title = {Beyond postpartum depression: posttraumatic stress-depressive response following childbirth.}, journal = {Archives of women's mental health}, volume = {23}, number = {4}, pages = {557-564}, pmid = {31650283}, issn = {1435-1102}, support = {R21 HD090396/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Comorbidity ; Delivery, Obstetric ; Depression/*epidemiology ; Depression, Postpartum/*epidemiology ; Female ; Humans ; Mental Health/statistics & numerical data ; Parturition/*psychology ; Postpartum Period/psychology ; Stress Disorders, Post-Traumatic/*epidemiology ; Surveys and Questionnaires ; }, abstract = {Although depression following childbirth is well recognized, much less is known about comorbid postpartum psychiatric conditions. Some women can endorse posttraumatic stress related to the childbirth experience accompanied by symptoms of depression. The objective of our study was to examine the nature of the comorbidity of symptoms of childbirth-related posttraumatic stress disorder (PTSD) and postpartum depression. We studied a sample of 685 women who were on average 3 months following childbirth and collected data about their mental health pertaining to PTSD, depression, general distress, and childbirth experience. The vast majority of women with elevated childbirth-related PTSD symptoms also endorsed elevated postpartum depression symptoms. Factor analysis revealed that symptoms of childbirth-related PTSD and postpartum depression loaded onto one single factor rather than two factors. Stepwise multi-nominal regression analysis revealed that childbirth stressors, including obstetric complications and peritraumatic distress in birth, predicted the likelihood of developing comorbid childbirth-related PTSD and postpartum depression, but not depression alone. The findings suggest that beyond postpartum depression, postpartum women suffer from a posttraumatic stress-depressive response in the wake of a traumatic childbirth experience. Increasing awareness in routine postpartum care about traumatic childbirth and its associated emotional sequela is warranted.}, } @article {pmid31648007, year = {2019}, author = {Zivony, A and Erel, H and Levy, DA}, title = {Multifactorial effects of aging on the orienting of visual attention.}, journal = {Experimental gerontology}, volume = {128}, number = {}, pages = {110757}, doi = {10.1016/j.exger.2019.110757}, pmid = {31648007}, issn = {1873-6815}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/*psychology ; Attention/*physiology ; *Cues ; Female ; Humans ; Male ; Orientation, Spatial/*physiology ; Reaction Time ; Young Adult ; }, abstract = {Differential sensitivity of brain areas to the effects of healthy aging may lead to multifactorial influences on the orienting of spatial attention. We examined how aging affects two key aspects of orienting: the benefits of orienting to valid spatial cues vs. the costs of re-orienting following invalid cues, and the impact on orienting of prior cue validity, in the context of different degrees of cue predictivity and types of cue manifestation. We analyzed accuracy and response time data from the performance of 103 older adults and 135 younger adults in three versions of the Attention Networks Test. Participants engaged in target discrimination following either locational cues that were generally non-predictive, locational cues that were generally predictive, or symbolic cues that were generally predictive. We found that healthy older adults did not exhibit greater re-orienting response time costs than younger adults across all cueing types, nor did they differ in the orienting benefits provided by predictive locational cues. However, older adults derived greater benefit from valid cues in a generally non-predictive cueing context, and lesser benefit from valid cues in a symbolic predictive cueing context. Additionally, aging had no impact on the effects of prior trial validity on subsequent trial validity benefits. A comprehensive appreciation of the effects of aging on attention may be informed by these distinctions.}, } @article {pmid31647159, year = {2020}, author = {Seckin, ZI and Brumble, LM and Libertin, CR}, title = {Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13202}, doi = {10.1111/tid.13202}, pmid = {31647159}, issn = {1399-3062}, mesh = {Adult ; Antibodies, Viral/*blood ; Chickenpox/etiology/immunology/prevention & control ; Communicable Disease Control/*methods ; Communicable Diseases/*etiology/immunology ; Humans ; Measles/etiology/immunology/prevention & control ; Mumps/etiology/immunology/prevention & control ; *Organ Transplantation ; *Referral and Consultation ; Retrospective Studies ; Rubella/etiology/immunology/prevention & control ; *Serologic Tests ; Vaccination ; }, abstract = {BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates.

METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC).

RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients, vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P < .001).

CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.}, } @article {pmid31642761, year = {2019}, author = {Dadia, T and Greenbaum, D}, title = {Neuralink: The Ethical 'Rithmatic of Reading and Writing to the Brain.}, journal = {AJOB neuroscience}, volume = {10}, number = {4}, pages = {187-189}, doi = {10.1080/21507740.2019.1665129}, pmid = {31642761}, issn = {2150-7759}, mesh = {Brain ; Morals ; *Reading ; *Writing ; }, } @article {pmid31642210, year = {2019}, author = {Wu, W and Wu, M and Peng, G and Shi, D and Zhang, J}, title = {Prognosis in triple-negative apocrine carcinomas of the breast: A population-based study.}, journal = {Cancer medicine}, volume = {8}, number = {18}, pages = {7523-7531}, pmid = {31642210}, issn = {2045-7634}, support = {2017AG100171//Foshan Science and Technology Bureau Foundation/International ; }, mesh = {Adolescent ; Adult ; Aged ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/mortality ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Public Health Surveillance ; SEER Program ; Triple Negative Breast Neoplasms/diagnosis/*epidemiology/mortality ; Young Adult ; }, abstract = {BACKGROUND: Triple-negative apocrine carcinoma (TNAC) of the breast is a very rare type of breast cancer. Furthermore, the clinicopathological features, prognosis, and potential impact of treatment strategies in TNAC remain unclear.

METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify breast cancer patients diagnosed between 2010 and 2016 with TNAC and triple-negative breast cancer (TNBC, IDC [invasive ductal carcinoma], NOS [not otherwise specified]). Chi-squared tests were used to examine the categorical variables between the two groups. Overall survival (OS) of TNAC and TNBC was assessed by Kaplan-Meier analyses and Cox regression. Breast cancer-specific survival (BCSS) was evaluated by Nelson-Aalen analyses and competing risk regression.

RESULTS: We identified 31 362 patients from the SEER database, including 366 patients with TNAC and 30 996 patients with TNBC. TNAC was correlated with older age, lower T stage and lower tumor grade. Patients with TNAC had better OS compared with TNBC patients; the 5-year OS rates were 82.2% vs 73.5% (P < .001). The breast cancer-related death rate was significantly lower in patients with TNAC than in patients with TNBC, with a 5-year cumulative incidence of 9.1% vs 22.9% (P < .001). Chemotherapy was significantly associated with improved OS in TNAC patients, but radiotherapy was not associated with OS in TNAC patients. In the multivariable Cox regression, TNAC was still associated with improved OS (HR [hazard ratio], 0.61; 95% CI [confidence interval] 0.45-0.83; P = .002). In the multivariable competing risk regression, the significantly higher BCSS in patients with TNAC compared patients with TNBC remained (subdistribution HR [SHR], 0.42; 95% CI, 0.27-0.64; P < .001).

CONCLUSION: Patients with TNAC had a better prognosis than patients with TNBC, and chemotherapy was associated with survival advantages in TNAC patients.}, } @article {pmid31639071, year = {2019}, author = {Lewis, GD and Xing, Y and Haque, W and Patel, T and Schwartz, M and Chen, A and Farach, A and Hatch, SS and Butler, EB and Chang, J and Teh, BS}, title = {Prognosis of lymphotropic invasive micropapillary breast carcinoma analyzed by using data from the National Cancer Database.}, journal = {Cancer communications (London, England)}, volume = {39}, number = {1}, pages = {60}, pmid = {31639071}, issn = {2523-3548}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality ; Carcinoma, Papillary/*mortality ; Databases, Factual ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB).

METHODS: Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log-rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS.

RESULTS: Overall, 2660 patients with IMPC met the selection criteria; the 5-year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node-negative patients, whereas patients with 1-3 positive nodes had similar OS to node-negative patients. Age < 65 years, receipt of radiotherapy, and estrogen receptor positivity were also associated with prolonged OS. The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy; there was no benefit for the patients undergoing mastectomy (regardless of nodal positivity/negativity).

CONCLUSIONS: Favorable prognostic factors of IMPC patients included age < 65 years, < 4 positive lymph nodes, receipt of radiotherapy, and estrogen receptor positivity. The results presented herein suggest a survival benefit associated with radiotherapy in IMPC treatment, though this may be limited to the patients treated with lumpectomy.}, } @article {pmid31632852, year = {2019}, author = {Chai, X and Sun, MY and Jia, HY and Wang, M and Cao, L and Li, ZW and Wang, DW}, title = {A prognostic nomogram for overall survival in male breast cancer with histology of infiltrating duct carcinoma after surgery.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e7837}, pmid = {31632852}, issn = {2167-8359}, abstract = {OBJECTIVE: The study was designed to construct and validate a nomogram for predicting overall survival (OS) of male breast cancer (MBC) patients with infiltrating duct carcinoma (IDC).

METHODS: The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) database between January 1, 2004 and December 31, 2013. Univariate and multivariate Cox proportional hazard (PH) regression models were performed. A nomogram was developed based on the significant prognostic indicators of OS. The discriminatory and predictive capacities of nomogram were assessed by Harrell's concordance index (C-index), calibration plots, area under the curve (AUC) and the decision curve analysis (DCA).

RESULTS: The median and maximal survival time of 1862 eligible patients were 49 and 131 months, respectively. Multivariate analysis showed that age (P < 0.0001), marital status (P = 0.002), T stage (P < 0.0001), N stage (P = 0.021), M stage (P < 0.0001), progesterone receptor (PR) (P = 0.046), human epidermal growth factor receptor-2 (HER2) (P = 0.009), and chemotherapy (P = 0.003) were independent prognostic indicators of IDC of MBC. The eight variables were then combined to construct a 3-and 5-year nomogram. The C-indexes of the nomogram were0.740 (95% confidence interval [CI] [0.709-0.771]) and 0.718 (95% CI [0.672-0.764]) for the internal validation and external validation, respectively. A better discriminatory capacity was observed in the nomogram compared with the SEER summary stage (P < 0.001) and AJCC TNM staging systems (6th edition; P < 0.001) with respect to OS prediction. Good consistency was detected between the nomogram prediction and actual findings, as indicated by calibration curves. The AUC for 3-and 5-year OS was 0.739 (95% CI [0.693-0.786]) and 0.764 (95% CI [0.725-0.803]) in the training cohort and 0.737 (95% CI [0.671-0.803]) and 0.735 (95% CI [0.678-0.793]) in the validation cohort, respectively. The DCA demonstrated that the survival nomogram was clinically useful.

CONCLUSIONS: The nomogram was able to more accurately predict 3-and 5-year OS of MBC patients with IDC histology than were existing models.}, } @article {pmid31630876, year = {2019}, author = {Dessauvagie, B and Thomas, A and Thomas, C and Robinson, C and Combrink, M and Budhavaram, V and Kunjuraman, B and Meehan, K and Sterrett, G and Harvey, J}, title = {Invasive lobular carcinoma of the breast: assessment of proliferative activity using automated Ki-67 immunostaining.}, journal = {Pathology}, volume = {51}, number = {7}, pages = {681-687}, doi = {10.1016/j.pathol.2019.08.004}, pmid = {31630876}, issn = {1465-3931}, mesh = {Adult ; Aged ; Algorithms ; Biomarkers, Tumor/*analysis ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Lobular/classification/*diagnostic imaging/pathology ; Cell Proliferation ; Cohort Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Middle Aged ; Neoplasm Grading ; Pilot Projects ; Prognosis ; }, abstract = {Invasive lobular carcinoma (ILC) is almost always classified as Nottingham histological grade 2. Despite this, prognosis is markedly varied, with some ILCs behaving more akin to grade 3 invasive ductal carcinoma (IDC). Methods to separate these aggressive ILCs are needed. Digital image analysis (DIA) of the Ki-67 biomarker has potential in this regard; thus, we sought to determine the feasibility of its use for automated evaluation of ILC. An initial pilot study demonstrated no ILC specific changes were required to our Ki-67 DIA algorithm for reproducible results. Subsequently, 42 consecutive cases of ILC were evaluated by visual mitosis counting in H&E stained sections and by DIA on Ki-67 stained sections. Ki-67 proliferative index (PI) DIA showed significant correlation with visual mitosis counting on H&E stained sections (rs=0.63; p<0.05), significant strong correlation (rs=0.78; p<0.05) and substantial agreement (κ=0.62) with manual/visual Ki-67 assessment and significant positive associations with grade, nodal status and 'pleomorphic' ILC subtype, and a wide stratification of values in classical/grade 2 ILC. In conclusion, DIA of Ki-67 PI in ILC is feasible, correlates with mitotic index, manual/visual Ki-67 PI and clinico-pathological variables. The broad stratification of Ki-67 PI in classical/grade 2 ILC supports its practicability as a biomarker with prognostic and predictive potential, although large studies with outcome data are required for validation.}, } @article {pmid31620685, year = {2019}, author = {Kanyılmaz, G and Yavuz, BB and Aktan, M and Karaağaç, M and Uyar, M and Fındık, S}, title = {Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors.}, journal = {European journal of breast health}, volume = {15}, number = {4}, pages = {256-261}, pmid = {31620685}, issn = {2587-0831}, abstract = {OBJECTIVE: The clinical feature of breast cancer is very heterogeneous because of the variable prognostic factors impact its behaviour. The aim of study is to find the prognostic importance of Ki-67 and to analyse the correlation between Ki-67 index and the other conventional prognostic factors in breast cancer patients.

MATERIALS AND METHODS: Between 2010 and 2017, patients with invasive ductal carcinoma who received radiotherapy after surgery were included in study. A single pathologist re-defined of all cases retrospectively. Ki-67 were established three categories based on Ki-67 levels: low (<10%), intermediate (10-25%) and high (>25%).

RESULTS: A total of 258 patients were included. 46 of 258 (18%) patients were in low, 82 of 258 (32%) patients were in intermediate and 130 of 258 (50%) patients were in high Ki-67 group. There were no correlations between menopausal status, age, and Ki-67 level. Low-pT stages tended to have low Ki-67 expression (p=0.07). Low-pN stages correlated with low Ki-67 values (p=0.007). Patients with ECE (+) were prone to have higher Ki-67 values (p=0.02). The significant correlation was seen between Ki-67 and tumour grading (p=<0.0001). Patients with LVI (+) had higher Ki-67 expression (p=0.007). Luminal A tumours were correlated with low Ki-67 group (p=<0.0001). Ki-67 values had significant effect on DFS (p=0.03) but not OS (p=0.09).

CONCLUSION: This study showed that high Ki-67 expression is associated with higher pT-stage, higher pN-stage, higher grade, ER/PR negativity, HER2/neu positivity, ECE and LVI positivity. The prognostic impact of Ki-67 was only demonstrated for DFS.}, } @article {pmid31620363, year = {2019}, author = {Bao, X and Shi, R and Zhang, K and Xin, S and Li, X and Zhao, Y and Wang, Y}, title = {Immune Landscape of Invasive Ductal Carcinoma Tumor Microenvironment Identifies a Prognostic and Immunotherapeutically Relevant Gene Signature.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {903}, pmid = {31620363}, issn = {2234-943X}, abstract = {Background: Invasive ductal carcinoma (IDC) is a clinically and molecularly distinct disease. Tumor microenvironment (TME) immune phenotypes play crucial roles in predicting clinical outcomes and therapeutic efficacy. Method: In this study, we depict the immune landscape of IDC by using transcriptome profiling and clinical characteristics retrieved from The Cancer Genome Atlas (TCGA) data portal. Immune cell infiltration was evaluated via single-sample gene set enrichment (ssGSEA) analysis and systematically correlated with genomic characteristics and clinicopathological features of IDC patients. Furthermore, an immune signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A random forest algorithm was applied to identify the most important somatic gene mutations associated with the constructed immune signature. A nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed by multivariate Cox regression. Results: The IDC were clustered into low immune infiltration, intermediate immune infiltration, and high immune infiltration by the immune landscape. The high infiltration group had a favorable survival probability compared with that of the low infiltration group. The low-risk score subtype identified by the immune signature was characterized by T cell-mediated immune activation. Additionally, activation of the interferon-α response, interferon-γ response, and TNF-α signaling via the NFκB pathway was observed in the low-risk score subtype, which indicated T cell activation and may be responsible for significantly favorable outcomes in IDC patients. A random forest algorithm identified the most important somatic gene mutations associated with the constructed immune signature. Furthermore, a nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed, revealing that the immune signature was an independent prognostic biomarker. Finally, the relationship of VEGFA, PD1, PDL-1, and CTLA-4 expression with the immune infiltration landscape and the immune signature was analyzed to interpret the responses of IDC patients to immunotherapy. Conclusion: Taken together, we performed a comprehensive evaluation of the immune landscape of IDC and constructed an immune signature related to the immune landscape. This analysis of TME immune infiltration landscape has shed light on how IDC respond to immunotherapy and may guide the development of novel drug combination strategies.}, } @article {pmid31619100, year = {2020}, author = {Kavesh, MH and Sanchez, D and Asirvatham, JR}, title = {Invasive Lobular Carcinoma With Extensive Clear Cells: A Pitfall in Diagnosis.}, journal = {International journal of surgical pathology}, volume = {28}, number = {2}, pages = {169-172}, doi = {10.1177/1066896919881705}, pmid = {31619100}, issn = {1940-2465}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/*pathology ; Diagnostic Errors ; Female ; Humans ; Ultrasonography, Interventional ; }, abstract = {Carcinomas in the breast with a predominantly clear cytoplasm are rare. In this article, we review the differential diagnosis of clear cell breast neoplasms and report a case of invasive lobular carcinoma with extensive clear cell morphology that was diagnosed as invasive ductal carcinoma, not otherwise specified, on ultrasound-guided biopsy. Lobular carcinomas with extensive clear cell change are unusual, but must be considered when evaluating a clear cell neoplasm in the breast.}, } @article {pmid31617074, year = {2020}, author = {Sethy, C and Goutam, K and Nayak, D and Pradhan, R and Molla, S and Chatterjee, S and Rout, N and Wyatt, MD and Narayan, S and Kundu, CN}, title = {Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.}, journal = {Journal of cancer research and clinical oncology}, volume = {146}, number = {1}, pages = {245-259}, pmid = {31617074}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism ; Cell Adhesion Molecules/biosynthesis/*genetics/metabolism ; Female ; Humans ; Middle Aged ; NF-kappa B/metabolism ; Neovascularization, Pathologic/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; }, abstract = {PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).

METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.

RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.

CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.}, } @article {pmid31612916, year = {2019}, author = {Shimmura, H and Kuramochi, H and Jibiki, N and Katagiri, S and Nishino, T and Araida, T}, title = {Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {11}, pages = {1049-1054}, doi = {10.1093/jjco/hyz141}, pmid = {31612916}, issn = {1465-3621}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; BRCA2 Protein/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Carcinoma, Pancreatic Ductal/*drug therapy ; Female ; Fluorouracil/therapeutic use ; Genetic Testing ; Germ Cells ; Germ-Line Mutation ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Middle Aged ; Mutation ; Oxaliplatin/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Pancreaticoduodenectomy ; }, abstract = {Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.}, } @article {pmid31612563, year = {2020}, author = {Schmidt, H and Connolly, C and Jaffer, S and Oza, T and Weltz, CR and Port, ER and Corben, A}, title = {Evaluation of surgically excised breast tissue microstructure using wide-field optical coherence tomography.}, journal = {The breast journal}, volume = {26}, number = {5}, pages = {917-923}, doi = {10.1111/tbj.13663}, pmid = {31612563}, issn = {1524-4741}, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; *Carcinoma, Ductal, Breast/surgery ; Cross-Sectional Studies ; Female ; Humans ; Mastectomy, Segmental ; Pilot Projects ; Tomography, Optical Coherence ; }, abstract = {BACKGROUND: Currently, positive margins at lumpectomy contribute to health care cost, patient anxiety, and treatment delay. Multiple technology solutions are being explored with the aim of lowering re-excision rates for breast-conserving surgery (BCS). We examined wide-field optical coherence tomography (WF-OCT), an innovative adjunct intraoperative imaging tool for tissue visualization of margins.

METHODS: This IRB-approved pilot study included women with invasive or in situ carcinoma scheduled for primary BCS. Lumpectomy specimens and any final/revised margins were imaged by optical coherence tomography immediately prior to standard histological processing. The optical coherence tomography used provided two-dimensional, cross-sectional, real-time depth visualization of the margin widths around excised specimens. A volume of images was captured for 10 × 10 cm tissue surface at high resolution (sub-30 μm) to a depth of 2 mm. Integrated interpretation was performed incorporating final pathology linked with the optical image data for correlation.

RESULTS: Wide-field optical coherence tomography was performed on 185 tissue samples (50 lumpectomy specimens and 135 additional margin shaves) in 50 subjects. Initial diagnosis was invasive ductal carcinoma (IDC) in 10, ductal carcinoma in situ (DCIS) in 14, IDC/DCIS in 22, invasive lobular carcinoma (ILC) in 2, ILC/DCIS in 1, and sarcoma in 1. Optical coherence tomography was concordant with final pathology in 178/185 tissue samples for overall accuracy of 86% and 96.2% (main specimen alone and main specimen + shave margins). Of seven samples that were discordant, 57% (4/7) were considered close (DCIS < 2 mm from margin) per final pathology.

CONCLUSION: Wide-field optical coherence tomography demonstrated concordance with histology at tissue margins, supporting its potential for use as a real-time adjunct intraoperative imaging tool for margin assessment. Further studies are needed for comprehensive evaluation in the intraoperative setting.}, } @article {pmid31605139, year = {2019}, author = {Bartelt, A and Leipsic, J and Weber, C}, title = {The new age of radiomic risk profiling: perivascular fat at the heart of the matter.}, journal = {European heart journal}, volume = {40}, number = {43}, pages = {3544-3546}, doi = {10.1093/eurheartj/ehz717}, pmid = {31605139}, issn = {1522-9645}, mesh = {Adipose Tissue ; *Computed Tomography Angiography ; Coronary Angiography ; Machine Learning ; *Tomography, X-Ray Computed ; }, } @article {pmid31598347, year = {2019}, author = {An, J and Yoo, Y and Kim, HG and Woo, J and Lee, KE and Kwon, H and Lim, W and Sung, SH and Paik, NS and Moon, BI}, title = {Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma.}, journal = {Journal of breast cancer}, volume = {22}, number = {3}, pages = {484-490}, pmid = {31598347}, issn = {1738-6756}, abstract = {Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.}, } @article {pmid31597373, year = {2019}, author = {Ginter, PS and Karagiannis, GS and Entenberg, D and Lin, Y and Condeelis, J and Jones, JG and Oktay, MH}, title = {Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases.}, journal = {Cancers}, volume = {11}, number = {10}, pages = {}, pmid = {31597373}, issn = {2072-6694}, support = {P01 CA100324/CA/NCI NIH HHS/United States ; CA216248/CA/NCI NIH HHS/United States ; R01 CA216248/CA/NCI NIH HHS/United States ; R01 CA150344/CA/NCI NIH HHS/United States ; CA100324/CA/NCI NIH HHS/United States ; }, abstract = {Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional "doorways" for hematogenous dissemination. Here, we studied a well-annotated case-control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels.}, } @article {pmid31594782, year = {2019}, author = {Jakharia-Shah, A and Wheatley, H and Beesley, M}, title = {Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.}, journal = {BMJ case reports}, volume = {12}, number = {10}, pages = {}, pmid = {31594782}, issn = {1757-790X}, mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Parotid Gland/*pathology/surgery ; Parotid Neoplasms/pathology/*secondary/surgery ; Positron Emission Tomography Computed Tomography/methods ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; }, abstract = {A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.}, } @article {pmid31584185, year = {2020}, author = {Xu, Q and Rangaswamy, US and Wang, W and Robbins, SH and Harper, J and Jin, H and Cheng, X}, title = {Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.}, journal = {International journal of cancer}, volume = {146}, number = {2}, pages = {531-541}, doi = {10.1002/ijc.32694}, pmid = {31584185}, issn = {1097-0215}, mesh = {Animals ; Chlorocebus aethiops ; Coculture Techniques ; *Cross-Priming ; Dendritic Cells/*immunology/metabolism ; Female ; HeLa Cells ; Humans ; Immunotherapy/*methods ; Interferon Type I/immunology/metabolism ; Neoplasms/immunology/*therapy ; Newcastle disease virus/genetics/immunology ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/genetics/immunology ; RNA/administration & dosage/genetics ; RNA, Viral/administration & dosage/genetics ; T-Lymphocytes/immunology ; Vero Cells ; }, abstract = {We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.}, } @article {pmid31583154, year = {2019}, author = {Jayarajah, U and Basnayake, O and Wijerathne, P and Jayasinghe, J and Samarasekera, DN and Seneviratne, S}, title = {A Rare Occurrence of Three Primary Malignancies of the Rectum, Breast, and Kidney in the Same Patient: A Case Report and Review of the Literature.}, journal = {Case reports in surgery}, volume = {2019}, number = {}, pages = {1716029}, pmid = {31583154}, issn = {2090-6900}, abstract = {An increasing number of patients with multiple primary cancers are encountered due to improved cancer detection, widespread cancer screening, and better cancer treatment. Here, we report such a patient without a family history of malignancies or a known genetic predisposition developing three primary malignancies of the rectum, breast, and kidney. A 63-year-old female who underwent an anterior resection for rectal cancer was detected to have an elevated carcinoembryonic antigen (CEA) level during a routine follow-up, 8 years after the initial surgery. Clinical examination revealed a left breast lump which was confirmed as invasive ductal carcinoma (pT3 pN0 cM0). Imaging and colonoscopy excluded a local recurrence. However, a right renal lesion suggestive of a renal cell carcinoma was detected (pT1a). She underwent left mastectomy with a sentinel lymph node biopsy and a right partial nephrectomy with a curative intent. Postoperatively, CEA levels declined to normal limits. Management of multiple primary malignancies poses a major challenge. A multidisciplinary approach and tailored decision-making for the individual patient help with the optimum outcome.}, } @article {pmid31583145, year = {2019}, author = {Al Khudari, R and Homsi, M and Al Zohaily, H and Saifo, MS}, title = {Primary Stromal Breast Sarcoma with Concomitant Contralateral Carcinoma: A Rare Case from Syria.}, journal = {Case reports in oncological medicine}, volume = {2019}, number = {}, pages = {6460847}, pmid = {31583145}, issn = {2090-6706}, abstract = {Bilateral breast cancers are rare cases encountered and are usually the same type in both sides. Only very few cases were reported to have different histological types of neoplasia involving sarcoma. Moreover, sarcomas rarely originate from the breast as a primary lesion whereas the common presentation is having angiosarcoma following radiotherapy. In this report, we present a rare case of a Syrian 43-year-old woman having two distinct primary lesions in the breasts: invasive ductal carcinoma and contralateral stromal sarcoma.}, } @article {pmid31583000, year = {2019}, author = {Jafarian, AH and Kooshkiforooshani, M and Rasoliostadi, A and Mohamadian Roshan, N}, title = {Vascular Mimicry Expression in Invasive Ductal Carcinoma; A New Technique for Prospect of Aggressiveness.}, journal = {Iranian journal of pathology}, volume = {14}, number = {3}, pages = {232-235}, pmid = {31583000}, issn = {1735-5303}, abstract = {BACKGROUND & OBJECTIVE: In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors.

METHODS: In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented.

RESULTS: The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression.

CONCLUSION: The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.}, } @article {pmid31578784, year = {2020}, author = {Patel, DP and Herrick, JS and Stoffel, JT and Elliott, SP and Lenherr, SM and Presson, AP and Welk, B and Jha, A and Myers, JB and , }, title = {Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.}, journal = {Neurourology and urodynamics}, volume = {39}, number = {1}, pages = {211-219}, doi = {10.1002/nau.24172}, pmid = {31578784}, issn = {1520-6777}, mesh = {Adult ; Female ; Health Behavior ; Humans ; Intermittent Urethral Catheterization/*adverse effects ; Male ; Middle Aged ; Patient Compliance ; Patient Satisfaction ; *Quality of Life ; Registries ; Spinal Cord Injuries/*complications ; Urinary Bladder, Neurogenic/*etiology ; Urinary Tract Infections/*etiology ; }, abstract = {INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation.

METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL.

RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties).

CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.}, } @article {pmid31576258, year = {2019}, author = {Marsili, C and Wilson, CM and Gura, N}, title = {Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.}, journal = {Cureus}, volume = {11}, number = {7}, pages = {e5265}, pmid = {31576258}, issn = {2168-8184}, abstract = {Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.}, } @article {pmid31572015, year = {2019}, author = {Gribsholt, SB and Pedersen, L and Richelsen, B and Thomsen, RW}, title = {Validity of ICD-10 diagnoses of overweight and obesity in Danish hospitals.}, journal = {Clinical epidemiology}, volume = {11}, number = {}, pages = {845-854}, pmid = {31572015}, issn = {1179-1349}, abstract = {PURPOSE: Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals.

PATIENTS AND METHODS: We linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m[2] as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m[2].

RESULTS: Of all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m[2], yielding a PPV of 87.6% (95% CI: 87.2-88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3-94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6-86.6). The PPV increased with higher patient age: from 75.3% (95% CI: 73.8-76.9) in those aged 18-29 years to 94.7% (95% CI: 92.6-96.9) in patients aged 80 years and above. Completeness of obesity/overweight diagnosis coding among patients recorded with BMI ≥25 kg/m[2] was only 10.9% (95% CI: 10.8-11.0).

CONCLUSION: Our findings indicate a high validity of the ICD-10 code E66 for overweight/obesity when recorded; however, completeness of coding was low. Nonetheless, ICD-10 discharge codes may be a suitable source of data on overweight/obesity for epidemiological research.}, } @article {pmid31568875, year = {2019}, author = {Escudero-Duch, C and Martin-Saavedra, F and Prieto, M and Sanchez-Casanova, S and Lopez, D and Sebastian, V and Arruebo, M and Santamaria, J and Vilaboa, N}, title = {Gold nanoparticles for the in situ polymerization of near-infrared responsive hydrogels based on fibrin.}, journal = {Acta biomaterialia}, volume = {100}, number = {}, pages = {306-315}, doi = {10.1016/j.actbio.2019.09.040}, pmid = {31568875}, issn = {1878-7568}, mesh = {Animals ; Cell Line ; Fibrin/*chemistry ; Gene Expression/drug effects ; Gold/*chemistry ; Humans ; Hydrogels/*chemistry ; *Infrared Rays ; Metal Nanoparticles/*chemistry/ultrastructure ; Mice ; *Polymerization ; Polymers/chemistry ; Temperature ; Thrombin/pharmacology ; Transgenes ; }, abstract = {Non-invasiveness and relative safety of photothermal therapy, which enables local hyperthermia of target tissues using a near infrared (NIR) laser, has attracted increasing interest. Due to their biocompatibility, amenability of synthesis and functionalization, gold nanoparticles have been investigated as therapeutic photothermal agents. In this work, hollow gold nanoparticles (HGNP) were coated with poly-l-lysine through the use of COOH-Poly(ethylene glycol)-SH as a covalent linker. The functionalized HGNP, which peak their surface plasmon resonance at 800 nm, can bind thrombin. Thrombin-conjugated HGNP conduct in situ fibrin polymerization, facilitating the process of generating photothermal matrices. Interestingly, the metallic core of thrombin-loaded HGNP fragmentates at physiological temperature. During polymerization process, matrices prepared with thrombin-loaded HGNP were loaded with genetically-modified stem cells that harbour a heat-activated and ligand-dependent gene switch for regulating transgene expression. NIR laser irradiation of resulting cell constructs in the presence of ligand successfully triggered transgene expression in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Current technological development allows synthesis of gold nanoparticles (GNP) in a wide range of shapes and sizes, consistently and at scale. GNP, stable and easily functionalized, show low cytotoxicity and high biocompatibility. Allied to that, GNP present optoelectronic properties that have been exploited in a range of biomedical applications. Following a layer-by-layer functionalization approach, we prepared hollow GNP coated with a positively charged copolymer that enabled thrombin conjugation. The resulting nanomaterial efficiently catalyzed the formation of fibrin hydrogels which convert energy of the near infrared (NIR) into heat. The resulting NIR-responsive hydrogels can function as scaffolding for cells capable of controlled gene expression triggered by optical hyperthermia, thus allowing the deployment of therapeutic gene products in desired spatiotemporal frameworks.}, } @article {pmid31566914, year = {2020}, author = {Sylvester-Armstrong, KR and Rasmussen, SA and Shoraka, M and Hendrickson, JE and Abu-Rustum, RS}, title = {Fetal sex discordance between noninvasive prenatal screening results and sonography: A single institution's experience and review of the literature.}, journal = {Birth defects research}, volume = {112}, number = {4}, pages = {339-349}, doi = {10.1002/bdr2.1594}, pmid = {31566914}, issn = {2472-1727}, mesh = {Adult ; Female ; Gestational Age ; Humans ; Karyotyping ; Male ; *Noninvasive Prenatal Testing ; Pregnancy ; *Turner Syndrome ; Ultrasonography ; Young Adult ; }, abstract = {BACKGROUND: With the increasing availability of noninvasive prenatal screening (NIPS) and high-resolution ultrasound, more cases of sex discordance are being identified in routine clinical practice. This can be a source of much concern for families and clinicians. Knowledge about the limitations of NIPS and reasons for discordant results are critical for counseling parents.

AIMS: Here, we present three cases from a single tertiary care referral center. We also review the literature to address potential limitations of NIPS in correctly identifying fetal sex chromosomes.

MATERIALS AND METHODS: After Institutional Review Board approval, cases of discordant fetal sex were identified using ICD-9 and ICD-10 codes. In addition, departmental counseling database and cytogenetics laboratory logbooks were reviewed.

RESULTS: In our first case, a 37-year-old G4 P2012 underwent NIPS at 11 weeks gestation and Monosomy X (associated with Turner syndrome) was identified. Morphological sonographic assessment at 20 weeks gestation was consistent with a female fetus following an amniocentesis at 16 weeks that revealed normal 46, XX karyotype. During the third trimester, the patient was diagnosed with Stage IV invasive ductal carcinoma of the breast. Postnatal follow-up of the neonate was consistent with a phenotypic female. In the second case, a 22-year-old G2 P1001 obese female underwent NIPS at 14 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was not consistent with a male fetus. The patient declined invasive testing. Postnatally, the karyotype was 46, XX and the neonate was phenotypically female. The reason for the discordant results was not identified. In the third case, a 25-year-old G1 P0 obese female underwent NIPS at 13 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was indeterminate; however, follow-up at 24 weeks was consistent with a female fetus. The patient declined invasive prenatal testing. Postnatally, the karyotype was 46, XX, and the neonate was phenotypically female with uterus present on ultrasound. The reason for the discordant results was not identified.

DISCUSSION: Our cases demonstrate possible limitations of NIPS in correctly identifying sex chromosomes.

CONCLUSIONS: Providers and patients need to be aware of these limitations, and invasive diagnostic prenatal testing should be offered in cases of discordance between NIPS and sonographic sex assessment.}, } @article {pmid31564808, year = {2019}, author = {Guo, R and Si, J and Xue, J and Su, Y and Mo, M and Yang, B and Zhang, Q and Chi, W and Chi, Y and Wu, J}, title = {Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999-2017.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {31}, number = {4}, pages = {653-662}, pmid = {31564808}, issn = {1000-9604}, abstract = {OBJECTIVE: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time.

METHODS: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and 1999-2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.

RESULTS: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort (from 35.3% to 41.9%; P=0.008), whereas it decreased in SEER cohort (from 42.4% to 33.0%; P<0.0001). The percentage of estrogen receptor (ER)-positive cancers was consistently increased in both the invasive ductal carcinoma (IDC) and DCIS patients in the two cohorts. Breast-conserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.

CONCLUSIONS: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial de-escalation in surgical therapies in young breast cancer patients.}, } @article {pmid31562689, year = {2020}, author = {Srour, MK and Donovan, C and Chung, A and Harit, A and Dadmanesh, F and Giuliano, AE and Amersi, F}, title = {Flat epithelial atypia on core needle biopsy does not always mandate excisional biopsy.}, journal = {The breast journal}, volume = {26}, number = {4}, pages = {679-684}, doi = {10.1111/tbj.13507}, pmid = {31562689}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology/surgery ; *Breast Neoplasms/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology/surgery ; Female ; Humans ; Hyperplasia/pathology ; Middle Aged ; Retrospective Studies ; }, abstract = {Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31-84) years. Thirty-two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non-pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty-two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow-up was 4.6 years (IQR 3.1-6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.}, } @article {pmid31562602, year = {2020}, author = {Ward, WH and DeMora, L and Handorf, E and Sigurdson, ER and Ross, EA and Daly, JM and Aggon, AA and Bleicher, RJ}, title = {Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {27}, number = {2}, pages = {386-396}, pmid = {31562602}, issn = {1534-4681}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*epidemiology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Incidence ; Mastectomy/*statistics & numerical data ; Middle Aged ; *Preoperative Care ; Prognosis ; Prospective Studies ; Time-to-Treatment/*statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND: Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion.

METHODS: A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (≤ 30, 31-60, 61-90, 91-120, 121-365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology.

RESULTS: Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05-1.10; P < 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9-96.1%) versus 94.9% (95% CI 94.6-95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11-1.15; P < 0.001).

CONCLUSIONS: Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised.}, } @article {pmid31559673, year = {2019}, author = {Glantschnig, C and Mattijssen, F and Vogl, ES and Ali Khan, A and Rios Garcia, M and Fischer, K and Müller, T and Uhlenhaut, H and Nawroth, P and Scheideler, M and Rose, AJ and Pellegata, N and Herzig, S}, title = {The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis.}, journal = {EMBO reports}, volume = {20}, number = {11}, pages = {e48552}, pmid = {31559673}, issn = {1469-3178}, support = {AMPro//Helmholtz Association/International ; SFB-TR 205//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Adipocytes, Brown/*metabolism ; Animals ; Body Weight ; Cold-Shock Response ; *Energy Metabolism ; Fasting ; *Homeostasis ; Mice ; Mice, Knockout ; Receptors, Glucocorticoid/*metabolism ; }, abstract = {Aberrant activity of the glucocorticoid (GC)/glucocorticoid receptor (GR) endocrine system has been linked to obesity-related metabolic dysfunction. Traditionally, the GC/GR axis has been believed to play a crucial role in adipose tissue formation and function in both, white (WAT) and brown adipose tissue (BAT). While recent studies have challenged this notion for WAT, the contribution of GC/GR signaling to BAT-dependent energy homeostasis remained unknown. Here, we have generated and characterized a BAT-specific GR-knockout mouse (GR[BATKO]), for the first time allowing to genetically interrogate the metabolic impact of BAT-GR. The HPA axis in GR[BATKO] mice was intact, as was the ability of mice to adapt to cold. BAT-GR was dispensable for the adaptation to fasting-feeding cycles and the development of diet-induced obesity. In obesity, glucose and lipid metabolism, insulin sensitivity, and food intake remained unchanged, aligning with the absence of changes in thermogenic gene expression. Together, we demonstrate that the GR in UCP1-positive BAT adipocytes plays a negligible role in systemic metabolism and BAT function, thereby opposing a long-standing paradigm in the field.}, } @article {pmid31558937, year = {2019}, author = {Saadallah, F and Bouraoui, I and Naija, L and Sakhri, S and Zemni, I and Hassouna, JB and Dhieb, TB and Bouzaiene, H and Rahal, K}, title = {Coexistence of invasive ductal breast carcinoma and fibroadenoma.}, journal = {The Pan African medical journal}, volume = {33}, number = {}, pages = {139}, pmid = {31558937}, issn = {1937-8688}, mesh = {Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/pathology/surgery ; Female ; Fibroadenoma/*diagnosis/pathology/surgery ; Humans ; Mammography/methods ; Middle Aged ; }, abstract = {Fibroadenomas are the most common breast disease that occurs usually in young. The coexistence of an invasive ductal carcinoma and a fibroadenoma in the ipsilateral breast is extremely rare. We present the case of a 52 years woman, presented to us for an upper-outer breast lump. Breast imaging concluded to tow contiguous lesions, one of them was suspicious. She had a conservative surgery. Histology concluded to a fibroadenoma and an invasive ductal carcinoma.}, } @article {pmid31550859, year = {2019}, author = {Wang, YT and Chen, ZJ and Zhang, D and Zhou, H and Cao, XC and Wang, X}, title = {[Effect of the primary tumor location on the prognosis of breast invasive ductal carcinoma patients treated with radical mastectomy].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {41}, number = {9}, pages = {686-692}, doi = {10.3760/cma.j.issn.0253-3766.2019.09.008}, pmid = {31550859}, issn = {0253-3766}, support = {81472472//National Natural Science Foundation of China/ ; }, mesh = {Breast Neoplasms/mortality/*pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/*pathology/surgery ; Humans ; Lymph Nodes ; Lymphatic Metastasis/pathology ; *Mastectomy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion: Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.}, } @article {pmid31544633, year = {2019}, author = {Sherman, M and Idan, Z and Greenbaum, D}, title = {Who Watches the Step-Watchers: The Ups and Downs of Turning Anecdotal Citizen Science into Actionable Clinical Data.}, journal = {The American journal of bioethics : AJOB}, volume = {19}, number = {8}, pages = {44-46}, doi = {10.1080/15265161.2019.1619873}, pmid = {31544633}, issn = {1536-0075}, mesh = {*Biomedical Research ; Humans ; }, } @article {pmid31540266, year = {2019}, author = {Santos, CS and Ozgur, R and Uzilday, B and Turkan, I and Roriz, M and Rangel, AOSS and Carvalho, SMP and Vasconcelos, MW}, title = {Understanding the Role of the Antioxidant System and the Tetrapyrrole Cycle in Iron Deficiency Chlorosis.}, journal = {Plants (Basel, Switzerland)}, volume = {8}, number = {9}, pages = {}, pmid = {31540266}, issn = {2223-7747}, support = {UID/Multi/50016/2019//Fundação para a Ciência e a Tecnologia/ ; PTDC/AGRPRO/3972/2014//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/78353/2011//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress often experienced by soybean, owing to the low solubility of iron in alkaline soils. Here, soybean lines with contrasting Fe efficiencies were analyzed to test the hypothesis that the Fe efficiency trait is linked to antioxidative stress signaling via proper management of tissue Fe accumulation and transport, which in turn influences the regulation of heme and non heme containing enzymes involved in Fe uptake and ROS scavenging. Inefficient plants displayed higher oxidative stress and lower ferric reductase activity, whereas root and leaf catalase activity were nine-fold and three-fold higher, respectively. Efficient plants do not activate their antioxidant system because there is no formation of ROS under iron deficiency; while inefficient plants are not able to deal with ROS produced under iron deficiency because ascorbate peroxidase and superoxide dismutase are not activated because of the lack of iron as a cofactor, and of heme as a constituent of those enzymes. Superoxide dismutase and peroxidase isoenzymatic regulation may play a determinant role: 10 superoxide dismutase isoenzymes were observed in both cultivars, but iron superoxide dismutase activity was only detected in efficient plants; 15 peroxidase isoenzymes were observed in the roots and trifoliate leaves of efficient and inefficient cultivars and peroxidase activity levels were only increased in roots of efficient plants.}, } @article {pmid31539353, year = {2019}, author = {Gonzalez, SM and Aguilar-Jimenez, W and Alvarez, N and Rugeles, MT}, title = {Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.}, journal = {Hormone molecular biology and clinical investigation}, volume = {40}, number = {1}, pages = {}, doi = {10.1515/hmbci-2019-0003}, pmid = {31539353}, issn = {1868-1891}, mesh = {CD4-Positive T-Lymphocytes/*drug effects/immunology/virology ; Cells, Cultured ; Cholecalciferol/*pharmacology ; Dendritic Cells/*drug effects/immunology/virology ; HIV Infections/*immunology/prevention & control/transmission/virology ; HIV-1/*drug effects/immunology/physiology ; Humans ; Immunologic Factors/pharmacology ; Monocytes/drug effects/immunology/virology ; Virus Internalization/drug effects ; Vitamins/*pharmacology ; }, abstract = {Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.}, } @article {pmid31538688, year = {2020}, author = {Haynes, HR and Rose, DSC}, title = {Synchronous small lymphocytic lymphoma and metastatic breast carcinoma in axillary lymph nodes: Preservation of follicular architecture only in the portions of affected lymph nodes involved by metastatic carcinoma.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {245-246}, doi = {10.1111/tbj.13538}, pmid = {31538688}, issn = {1524-4741}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {We present a case of metastatic ductal carcinoma of breast with the incidental discovery of small lymphocytic lymphoma (SLL) in regional axillary nodes. The co-occurence of metastatic carcinoma and low-grade lymphoma in lymph nodes is rare but well recognized. However, in this case, in the lymph nodes in which sizeable metastatic carcinoma deposits were present, the follicular structures between the sinusoidal carcinomatous infiltrates were preserved, whereas the uninvolved portions of the nodes were overrun by SLL. This is the first description of this phenomenon. We suggest that further cases displaying this previously unpublished pattern are collated in order that we may begin to investigate the underlying etiological mediators.}, } @article {pmid31536600, year = {2019}, author = {Groener, JB and Valkanou, A and Kender, Z and Pfeiffenberger, J and Kihm, L and Fleming, T and Nawroth, PP and Kopf, S}, title = {Asprosin response in hypoglycemia is not related to hypoglycemia unawareness but rather to insulin resistance in type 1 diabetes.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0222771}, pmid = {31536600}, issn = {1932-6203}, mesh = {Adult ; Aged ; Blood Glucose/metabolism ; Cohort Studies ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1/*blood ; Female ; Fibrillin-1 ; Glucose Tolerance Test ; Humans ; Hypoglycemia/*blood ; Insulin/blood ; *Insulin Resistance ; Liver/metabolism/pathology ; Male ; Microfilament Proteins/*blood ; Middle Aged ; Non-alcoholic Fatty Liver Disease/blood/pathology ; Peptide Fragments/*blood ; Peptide Hormones/*blood ; Pilot Projects ; }, abstract = {Asprosin is a counter-regulatory hormone to insulin which plays a role in fasting. It may therefore also play a role in hypoglycaemia unawareness, which has been subsequently examined in this pilot study. Intravenous glucose tolerance test was used to induce controlled hyperglycemia whereas a hyperinsulinemic clamp test was used to induce a controlled hypoglycaemia in 15 patients with diabetes type 1, with and without hypoglycaemia unawareness. Changes in asprosin plasma levels did not differ between patients with and without hypoglycaemia unawareness. However, nine patients with insulin resistance as well as higher liver stiffness values and low-density lipoprotein but lower high-density lipoprotein levels did not show the expected increase in asprosin plasma levels during hypoglycemia. Therefore, insulin resistance and alterations in liver structure, most likely early stages of non-alcoholic fatty liver disease, seem to be relevant in type 1 diabetes and do not only lead to elevated plasma levels of asprosin, but also to a blunted asprosin response in hypoglycemia.}, } @article {pmid31534228, year = {2019}, author = {Ardi, Z and Richter-Levin, A and Xu, L and Cao, X and Volkmer, H and Stork, O and Richter-Levin, G}, title = {The role of the GABAA receptor Alpha 1 subunit in the ventral hippocampus in stress resilience.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13513}, pmid = {31534228}, issn = {2045-2322}, mesh = {Animals ; Anxiety/metabolism ; Behavior, Animal/physiology ; Environment ; Exploratory Behavior/physiology ; Hippocampus/*metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A/*metabolism ; Resilience, Psychological ; Stress Disorders, Post-Traumatic/metabolism/prevention & control ; Stress, Psychological/*metabolism ; }, abstract = {Pre-pubertal stress increases post-traumatic stress disorder (PTSD) susceptibility. We have previously demonstrated that enriched environment (EE) intervention immediately after pre-pubertal stress protects from the effects of trauma in adulthood. Here, we examined whether exposure to EE would also be beneficial if applied after exposure to trauma in adulthood. We have recently shown that exposure to juvenile stress and under-water trauma (UWT) is associated with increased expression of GABAA receptor subunit α1 in the ventral hippocampus. However, differentiating between affected and unaffected individuals, this increased expression was confined to stress-exposed, behaviorally unaffected individuals, suggesting upregulation of α1 expression as a potential mechanism of resilience. We now examined whether EE-induced resilience renders increased expression of α1 in the ventral hippocampus redundant when facing a trauma later in life. Adult rats were exposed to UWT, with pre-exposure to juvenile stress, and tested in the open field and elevated plus maze paradigms four weeks later. EE exposure during juvenility prevented pre-pubertal stress-induced vulnerability, but not if performed following UWT in adulthood. Furthermore, juvenile EE exposure prevented the trauma-associated increase in α1 expression levels. Our findings emphasize the importance of early interventions in order to reduce the likelihood of developing psychopathologies in adulthood.}, } @article {pmid31533746, year = {2019}, author = {Mackeprang, PH and Vuong, D and Volken, W and Henzen, D and Schmidhalter, D and Malthaner, M and Mueller, S and Frei, D and Kilby, W and Aebersold, DM and Fix, MK and Manser, P}, title = {Benchmarking Monte-Carlo dose calculation for MLC CyberKnife treatments.}, journal = {Radiation oncology (London, England)}, volume = {14}, number = {1}, pages = {172}, pmid = {31533746}, issn = {1748-717X}, mesh = {*Algorithms ; Benchmarking ; Humans ; Lung Neoplasms/pathology/*surgery ; Male ; *Monte Carlo Method ; Organs at Risk/radiation effects ; *Phantoms, Imaging ; Prognosis ; Prostatic Neoplasms/pathology/*surgery ; Radiosurgery/*instrumentation/*methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy, Intensity-Modulated/methods ; }, abstract = {BACKGROUND: Vendor-independent Monte Carlo (MC) dose calculation (IDC) for patient-specific quality assurance of multi-leaf collimator (MLC) based CyberKnife treatments is used to benchmark and validate the commercial MC dose calculation engine for MLC based treatments built into the CyberKnife treatment planning system (Precision MC).

METHODS: The benchmark included dose profiles in water in 15 mm depth and depth dose curves of rectangular MLC shaped fields ranging from 7.6 mm × 7.7 mm to 115.0 mm  × 100.1 mm, which were compared between IDC, Precision MC and measurements in terms of dose difference and distance to agreement. Dose distributions of three phantom cases and seven clinical lung cases were calculated using both IDC and Precision MC. The lung PTVs ranged from 14 cm[3] to 93 cm[3]. Quantitative comparison of these dose distributions was performed using dose-volume parameters and 3D gamma analysis with 2% global dose difference and 1 mm distance criteria and a global 10% dose threshold. Time to calculate dose distributions was recorded and efficiency was assessed.

RESULTS: Absolute dose profiles in 15 mm depth in water showed agreement between Precision MC and IDC within 3.1% or 1 mm. Depth dose curves agreed within 2.3% / 1 mm. For the phantom and clinical lung cases, mean PTV doses differed from - 1.0 to + 2.3% between IDC and Precision MC and gamma passing rates were > =98.1% for all multiple beam treatment plans. For the lung cases, lung V20 agreed within ±1.5%. Calculation times ranged from 2.2 min (for 39 cm[3] PTV at 1.0 × 1.0 × 2.5 mm[3] native CT resolution) to 8.1 min (93 cm[3] at 1.1 × 1.1 × 1.0 mm[3]), at 2% uncertainty for Precision MC for the 7 examined lung cases and 4-6 h for IDC, which, however, is not optimized for efficiency but used as a gold standard for accuracy.

CONCLUSIONS: Both accuracy and efficiency of Precision MC in the context of MLC based planning for the CyberKnife M6 system were benchmarked against MC based IDC framework. Precision MC is used in clinical practice at our institute.}, } @article {pmid31530092, year = {2020}, author = {Mikulincer, M and Agam, T and Shaver, PR}, title = {A secure base for mindful dreaming: dispositional and contextually variable attachment security and the experiential quality of dreams.}, journal = {Attachment & human development}, volume = {22}, number = {6}, pages = {606-626}, doi = {10.1080/14616734.2019.1666288}, pmid = {31530092}, issn = {1469-2988}, mesh = {Adult ; Dreams/*psychology ; Female ; Humans ; Israel ; Male ; Mental Health ; Mindfulness ; *Object Attachment ; Young Adult ; }, abstract = {In this study, we examined the utility of attachment theory for explaining individual differences in dream experiences. Seventy-six Israeli undergraduates completed a measure of attachment anxiety and avoidance and participated in a daily diary study for 15 consecutive days. Each evening, they rated their daily sense of attachment security. Each morning, they described in writing any dreams they recalled and rated the extent to which they (a) were aware of their sensations and mental states while dreaming and (b) reflected on their subjective experience during the dream. Two judges made similar ratings for each dream. Dispositional attachment anxiety and avoidance were associated with lower levels of within-dream awareness and reflection across the 15-day period. In addition, attachment security on a given day was associated with higher within-dream awareness and reflection that night. The findings provide new evidence concerning the contribution of attachment orientations to the experiential quality of dreams.}, } @article {pmid31529566, year = {2019}, author = {van Kooten, XF and Petrini, LFT and Kashyap, A and Voith von Voithenberg, L and Bercovici, M and Kaigala, GV}, title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {58}, number = {43}, pages = {15259-15262}, doi = {10.1002/anie.201907150}, pmid = {31529566}, issn = {1521-3773}, support = {607322//FP7 People: Marie-Curie Actions/International ; 727761//H2020 European Research Council/International ; }, mesh = {Breast Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis/metabolism ; Female ; Formaldehyde/chemistry ; Genotype ; Humans ; MCF-7 Cells ; Microscopy, Confocal ; Paraffin Embedding ; Point Mutation ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.}, } @article {pmid31527734, year = {2019}, author = {Abbasi, S and Le, M and Sonier, B and Dinakaran, D and Bigras, G and Bell, K and Mackey, JR and Haji Reza, P}, title = {All-optical Reflection-mode Microscopic Histology of Unstained Human Tissues.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13392}, pmid = {31527734}, issn = {2045-2322}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology ; Eosine Yellowish-(YS)/*chemistry ; Female ; Gastrointestinal Neoplasms/diagnostic imaging/*pathology ; Hematoxylin/*chemistry ; Humans ; Microscopy/*methods ; Pancreatic Neoplasms/diagnostic imaging/*pathology ; Tonsillar Neoplasms/diagnostic imaging/*pathology ; }, abstract = {Surgical oncologists depend heavily on visual field acuity during cancer resection surgeries for in-situ margin assessment. Clinicians must wait up to two weeks for results from a pathology lab to confirm a post-operative diagnosis, potentially resulting in subsequent treatments. Currently, there are no clinical tools that can visualize diagnostically pertinent tissue information in-situ. Here, we present the first microscopy capable of non-contact label-free visualization of human cellular morphology in a reflection-mode apparatus. This is possible with the recently reported imaging modality called photoacoustic remote sensing microscopy which enables non-contact detection of optical absorption contrast. By taking advantage of the 266-nanometer optical absorption peak of DNA, photoacoustic remote sensing is efficacious in recovering qualitatively similar nuclear information in comparison to that provided by the hematoxylin stain in the gold-standard hematoxylin and eosin (H&E) prepared samples. A photoacoustic remote sensing system was employed utilizing a 266-nanometer pulsed excitation beam to induce photoacoustic pressures within the sample resulting in refractive index modulation of the optical absorber. A 1310-nanometer continuous-wave interrogation beam detects these perturbed regions as back reflected intensity variations due to the changes in the local optical properties. Using this technique, clinically useful histologic images of human tissue samples including breast cancer (invasive ductal carcinoma), tonsil, gastrointestinal, and pancreatic tissue images were formed. These were qualitatively comparable to standard H&E prepared samples.}, } @article {pmid31524947, year = {2020}, author = {Ohe, R and Aung, NY and Tamura, Y and Kabasawa, T and Utsunomiya, A and Tamazawa, N and Kitaoka, T and Meng, HX and Shibata, K and Yamakawa, M}, title = {Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.}, journal = {Histology and histopathology}, volume = {35}, number = {5}, pages = {481-488}, pmid = {31524947}, issn = {1699-5848}, support = {JP19K16577//Japan Society for the Promotion of Science (JSPS)/ ; JP17K08736//Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Adult ; Antigens, CD/*metabolism ; Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast Neoplasms/diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Dendritic Cells/metabolism ; Diagnosis, Differential ; Epithelial Cells/metabolism ; Female ; Humans ; Lectins, C-Type/*metabolism ; Middle Aged ; Minor Histocompatibility Antigens/*metabolism ; Receptors, Cell Surface/*metabolism ; }, abstract = {BACKGROUND: CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer.

MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining.

RESULTS: In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01).

CONCLUSION: Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.}, } @article {pmid31517740, year = {2020}, author = {Gemici, AA and Ozal, ST and Hocaoglu, E and Inci, E}, title = {Relationship Between Shear Wave Elastography Findings and Histologic Prognostic Factors of Invasive Breast Cancer.}, journal = {Ultrasound quarterly}, volume = {36}, number = {1}, pages = {79-83}, doi = {10.1097/RUQ.0000000000000471}, pmid = {31517740}, issn = {1536-0253}, mesh = {Adult ; Aged ; Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Prospective Studies ; Turkey ; Ultrasonography, Mammary/*methods ; }, abstract = {OBJECTIVE: Shear wave elastography (SWE) is an adjunct to grayscale ultrasound examinations for evaluating breast masses. This study aimed to determine the SWE features that correlated with prognostic parameters for breast cancer.

METHODS: Between January 2018 and May 2018, 80 patients who were confirmed to have invasive cancers by core-needle biopsy and who were scheduled for surgery were imaged using B-mode ultrasound and SWE. Measurements were taken from a region of interest positioned over the stiffest part of the peripheral zone and mass. Three measurements were taken, and the average of the mean stiffness value was used for analysis.

RESULTS: The mean tumor size, elasticity value of tumors, and elasticity of the peripheral zone were 2.9 ± 1.48 cm (range, 0.6-8 cm), 154.8 ± 8.55 kPa (range, 116.25-179 kPa), and 171.34 ± 5.22 kPa (range, 150.95-182.43 kPa), respectively. The types of breast cancer included were invasive ductal carcinoma (n = 71 [88.75%]; 69 invasive ductal carcinoma not otherwise specified, 1 solid papillary carcinoma, and 1 invasive micropapillary carcinoma), invasive lobular carcinoma (n = 2 [2.5%]), mixed invasive ductal and lobular carcinoma (n = 4 [5%]), mucinous carcinoma (n = 2 [2.5%]), and metaplastic cancer (n = 1 [1.25%]). A strong correlation was found between mean elasticity values and tumor grade (P = 0.018) and between mean elasticity values and lymphovascular invasion (LVI) positivity (P = 0.008). There were no significant differences between SWE values and tumor diameter or between histological tumor characteristics and SWE.

CONCLUSIONS: We found that some clinicohistopathologic features of poor prognosis had higher elasticity values than those of favorable prognosis.}, } @article {pmid31513315, year = {2020}, author = {Abdel Hadi, M and Al Muhanna, A and Alratroot, J and Shawarby, MA}, title = {Angiocentric invasive ductal carcinoma: Breast images.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {295-296}, doi = {10.1111/tbj.13553}, pmid = {31513315}, issn = {1524-4741}, mesh = {Aged ; Axilla ; Breast Neoplasms/blood supply/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/blood supply/*diagnostic imaging/pathology ; Female ; Humans ; Lymph Nodes/blood supply/*diagnostic imaging/pathology ; Tomography, X-Ray Computed ; Ultrasonography, Doppler ; Ultrasonography, Mammary ; }, } @article {pmid31512354, year = {2020}, author = {Ali Mlees, M}, title = {Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.}, journal = {The breast journal}, volume = {26}, number = {2}, pages = {139-143}, doi = {10.1111/tbj.13493}, pmid = {31512354}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Dilatation, Pathologic/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Image-Guided Biopsy ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Papilloma/*diagnosis/pathology ; Ultrasonography, Interventional ; }, abstract = {Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.}, } @article {pmid31508769, year = {2019}, author = {Couto, MSA and Firme, VAC and Guerra, MR and Bustamante-Teixeira, MT}, title = {The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.}, journal = {Ciencia & saude coletiva}, volume = {24}, number = {9}, pages = {3517-3528}, doi = {10.1590/1413-81232018249.31402017}, pmid = {31508769}, issn = {1678-4561}, mesh = {Brazil/epidemiology ; Breast Neoplasms/*mortality ; Cause of Death/*trends ; Cities/statistics & numerical data ; Female ; Humans ; Mortality/*trends ; }, abstract = {The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.}, } @article {pmid31503011, year = {2020}, author = {Shabihkhani, M and Simpson, JF and White, MJ and Cimino-Mathews, A and Argani, P}, title = {Artifactual Displacement of Ductal Carcinoma In Situ (ADDCIS) (Toothpaste Effect): A Mimicker of Invasive Ductal Carcinoma.}, journal = {The American journal of surgical pathology}, volume = {44}, number = {1}, pages = {120-128}, doi = {10.1097/PAS.0000000000001370}, pmid = {31503011}, issn = {1532-0979}, mesh = {Adult ; Aged ; *Artifacts ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prospective Studies ; }, abstract = {Needle tract displacement is a recognized mimicker of invasive ductal carcinoma (IDC). Artifactual displacement of ductal carcinoma in situ (ADDCIS) unassociated with needle tracts may occur secondary to mechanical compression of breast specimens but has not been systematically studied. We identified 16 cases of ADDCIS unassociated with needle tract changes; the majority (75%) were internal referrals to the breast pathology service to rule out IDC, 19% were received as external diagnostic consultations to rule out IDC, and 6% were routine second review cases originally diagnosed as IDC at an outside hospital. The majority (62.5%) of ADDCIS occurred in lumpectomies, whereas 25% occurred in mastectomies and 12.5% in core biopsies. ADDCIS foci ranged from <1 to 5 mm; however, all ADDCIS spanning >4 mm demonstrated a linear pattern of displacement. In all cases, ADDCIS involved mammary stroma in a nonlobular distribution; in half, ADDCIS extended between benign lobules. Immunohistochemistry revealed no myoepithelial cells around the ADDCIS (n=7), adding to the concern for IDC. However, in contrast to most IDC, ADDCIS lacked stromal reaction and showed degenerative, smudged chromatin. None of the 9 patients with significant follow-up (mean, 7 y) developed metastasis. All received further local therapy for DCIS (5 radiation, 4 completion mastectomy); 1 received adjuvant systemic therapy (hormone therapy for contralateral IDC). In conclusion, ADDCIS mimics IDC, particularly given its permeative pattern and absence of myoepithelial cells. ADDCIS is most common in lumpectomies but can occur in mastectomies or core biopsies. Diagnostic clues include smudged nuclear chromatin, lack of stromal response, and linear pattern of displacement in larger lesions. The benign follow-up without systemic therapy supports our view that ADDCIS does not represent true IDC.}, } @article {pmid31502960, year = {2020}, author = {Hou, R and Mazurowski, MA and Grimm, LJ and Marks, JR and King, LM and Maley, CC and Hwang, ES and Lo, JY}, title = {Prediction of Upstaged Ductal Carcinoma In Situ Using Forced Labeling and Domain Adaptation.}, journal = {IEEE transactions on bio-medical engineering}, volume = {67}, number = {6}, pages = {1565-1572}, pmid = {31502960}, issn = {1558-2531}, support = {R01 CA185138/CA/NCI NIH HHS/United States ; R01 CA222508/CA/NCI NIH HHS/United States ; C38317/A24043/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Breast/diagnostic imaging ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Female ; Humans ; Mammography ; ROC Curve ; Retrospective Studies ; }, abstract = {OBJECTIVE: The goal of this study is to use adjunctive classes to improve a predictive model whose performance is limited by the common problems of small numbers of primary cases, high feature dimensionality, and poor class separability. Specifically, our clinical task is to use mammographic features to predict whether ductal carcinoma in situ (DCIS) identified at needle core biopsy will be later upstaged or shown to contain invasive breast cancer.

METHODS: To improve the prediction of pure DCIS (negative) versus upstaged DCIS (positive) cases, this study considers the adjunctive roles of two related classes: atypical ductal hyperplasia (ADH), a non-cancer type of breast abnormity, and invasive ductal carcinoma (IDC), with 113 computer vision based mammographic features extracted from each case. To improve the baseline Model A's classification of pure vs. upstaged DCIS, we designed three different strategies (Models B, C, D) with different ways of embedding features or inputs.

RESULTS: Based on ROC analysis, the baseline Model A performed with AUC of 0.614 (95% CI, 0.496-0.733). All three new models performed better than the baseline, with domain adaptation (Model D) performing the best with an AUC of 0.697 (95% CI, 0.595-0.797).

CONCLUSION: We improved the prediction performance of DCIS upstaging by embedding two related pathology classes in different training phases.

SIGNIFICANCE: The three new strategies of embedding related class data all outperformed the baseline model, thus demonstrating not only feature similarities among these different classes, but also the potential for improving classification by using other related classes.}, } @article {pmid31497220, year = {2019}, author = {Peng, GL and Li, L and Guo, YW and Yu, P and Yin, XJ and Wang, S and Liu, CP}, title = {CD8[+] cytotoxic and FoxP3[+] regulatory T lymphocytes serve as prognostic factors in breast cancer.}, journal = {American journal of translational research}, volume = {11}, number = {8}, pages = {5039-5053}, pmid = {31497220}, issn = {1943-8141}, abstract = {BACKGROUND: There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3[+] regulatory T cells (Tregs), CD8[+] cytotoxic T lymphocytes (CTLs), clinicopathological features, and prognosis in patients with breast cancer.

METHODS: Immunohistochemistry was used to detect the expression levels and localization of FoxP3 and CD8. One-sample t-test, one-way analysis of variance, and Kaplan-Meier log-rank tests were used to analyze correlations between the expression levels of CD8 and FoxP3; Kaplan-Meier Log-rank test was used to analyze clinicopathological features to explore the prognostic significance of CD8 and FoxP3 in patients with breast cancer.

RESULTS: FoxP3 expression in the tumor bed was higher than that in the stroma, while CD8 was primarily expressed in the stroma. CD8 expression was associated with favorable prognostic factors. However, FoxP3 expression and an increased ratio of total FoxP3[+] Tregs to CD8[+] CTLs were significantly correlated with unfavorable prognostic factors. Additionally, an increased ratio was associated with molecular subtypes (ER[+]Her2[+], ER[+]Her2[-], ER[-]Her2[+], and ER[-]Her2[-]) of breast cancer. Overexpression of FoxP3 and a high FoxP3[+]/CD8[+] ratio were correlated with poor overall survival (OS) and disease-free survival (DFS). However, CD8 expression only affected OS in patients with breast cancer.

CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8[+] CTLs were associated with a good prognosis, while FoxP3[+] Tregs were associated with adverse outcomes in patients with breast cancer. CD8[+] CTLs and FoxP3[+] Tregs are potential predictive prognostic factors for patients with breast cancer.}, } @article {pmid31488082, year = {2019}, author = {McQuerry, JA and Jenkins, DF and Yost, SE and Zhang, Y and Schmolze, D and Johnson, WE and Yuan, Y and Bild, AH}, title = {Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {881}, pmid = {31488082}, issn = {1471-2407}, support = {U54CA209978/NH/NIH HHS/United States ; U54 CA209978/CA/NCI NIH HHS/United States ; U01 CA220413/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; R01 GM127430/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bcl-2-Like Protein 11/metabolism ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Osteonectin/genetics ; Phenotype ; Prognosis ; RNA-Seq/methods ; Receptors, Growth Factor/*metabolism ; Signal Transduction/*genetics ; Snail Family Transcription Factors/metabolism ; Transcriptome/*genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).

METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.

RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.

CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.}, } @article {pmid31486035, year = {2020}, author = {Delaunay, T and Achard, C and Grégoire, M and Tangy, F and Boisgerault, N and Fonteneau, JF}, title = {A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2058}, number = {}, pages = {127-132}, doi = {10.1007/978-1-4939-9794-7_8}, pmid = {31486035}, issn = {1940-6029}, mesh = {Animals ; Antigen-Presenting Cells/immunology/metabolism ; Cell Death/immunology ; Dendritic Cells/immunology/metabolism ; Genetic Therapy/methods ; Genetic Vectors/*genetics ; Humans ; *Immunomodulation ; Immunophenotyping ; Monocytes/immunology/metabolism ; Neoplasms/*immunology/metabolism/pathology/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/*genetics/immunology ; }, abstract = {Oncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC).}, } @article {pmid31482514, year = {2020}, author = {Cohen, R and Moed, A and Shoshani, A and Roth, G and Kanat-Maymon, Y}, title = {Teachers' Conditional Regard and Students' Need Satisfaction and Agentic Engagement: A Multilevel Motivation Mediation Model.}, journal = {Journal of youth and adolescence}, volume = {49}, number = {4}, pages = {790-803}, pmid = {31482514}, issn = {1573-6601}, mesh = {Adolescent ; Adolescent Development ; Female ; Humans ; Interpersonal Relations ; Male ; *Motivation ; *Personal Autonomy ; *Personal Satisfaction ; School Teachers/*psychology ; Students/*psychology ; }, abstract = {Teachers' conditional positive regard and conditional negative regard are common motivational techniques in the classroom. This study investigated their respective effects on adolescent students' agentic engagement, while considering students' basic psychological needs for autonomy and relatedness as potential mediators. Data collected from 30 teachers and 651 7th to 10th graders (52% female) were used to test a multilevel mediation model. The results indicated that teachers' conditional negative regard undermined students' agentic engagement by frustrating both of their autonomy and relatedness needs. Teachers' conditional positive regard thwarted students' sense of autonomy, which consequently undermined their agentic engagement. The findings are discussed in terms of conditional positive and negative regard as undesirable classroom motivational practices and the mechanisms through which they operate. The discussion also notes the importance of investigating contextual factors at the classroom level.}, } @article {pmid31478561, year = {2019}, author = {Liu, RL and Shi, ZQ and Wang, XY and Li, ZF and Li, G}, title = {Two Highly Stable Proton Conductive Cobalt(II)-Organic Frameworks as Impedance Sensors for Formic Acid.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {25}, number = {62}, pages = {14108-14116}, doi = {10.1002/chem.201902169}, pmid = {31478561}, issn = {1521-3765}, support = {21571156//the National Science Foundation of China/ ; }, abstract = {Metal-organic frameworks (MOFs) have been extensively explored as advanced chemical sensors in recent years. However, there are few studies on MOFs as acidic gas sensors, especially proton conductive MOFs. In this work, two new proton-conducting 3D MOFs, {[Co3 (p-CPhHIDC)2 (4,4'-bipy)(H2 O)]⋅2 H2 O} n (1) (p-CPhH4 IDC=2-(4-carboxylphenyl)-1 H-imidazole-4,5-dicarboxylic acid; 4,4'-bipy=4,4'-bipyridine) and {[Co3 (p-CPhHIDC)2 (bpe)(H2 O)]⋅3 H2 O} n (2) (bpe=trans-1,2-bis(4-pyridyl)ethylene) have been solvothermally prepared and investigated their formic acid sensing properties. Both MOFs 1 and 2 show temperature- and humidity-dependent proton conductive properties and exhibit optimized proton conductivities of 1.04×10[-3] and 7.02×10[-4] S cm at 98 % relative humidity (RH) and 100 °C, respectively. The large number of uncoordinated carboxylic acid sites, free and coordination water molecules, and hydrogen-bonding networks inside the frameworks are favorable to the proton transfer. By measuring the impedance values after exposure to formic acid vapor at 98 % or 68 % RH and 25 °C, both MOFs indicate reproducibly high sensitivity to the analyte. The detection limit of formic acid vapor is as low as 35 ppm for 1 and 70 ppm for 2. Meanwhile, both MOFs also show commendable selectivity towards formic acid among interfering solutions. The proton conducting and formic acid sensing mechanisms have been suggested according to the structural analysis, Ea calculations, N2 and water vapor absorptions, PXRD and SEM measurements. This work will open a new avenue for proton-conductive MOF-based impedance sensors and promote the potential application of these MOFs for indirectly monitoring the concentrations of formic acid vapors.}, } @article {pmid31470420, year = {2019}, author = {Fan, M and Liu, Z and Xie, S and Xu, M and Wang, S and Gao, X and Li, L}, title = {Integration of dynamic contrast-enhanced magnetic resonance imaging and T2-weighted imaging radiomic features by a canonical correlation analysis-based feature fusion method to predict histological grade in ductal breast carcinoma.}, journal = {Physics in medicine and biology}, volume = {64}, number = {21}, pages = {215001}, doi = {10.1088/1361-6560/ab3fd3}, pmid = {31470420}, issn = {1361-6560}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; ROC Curve ; Support Vector Machine ; }, abstract = {Tumour histological grade has prognostic implications in breast cancer. Tumour features in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and T2-weighted (T2W) imaging can provide related and complementary information in the analysis of breast lesions to improve MRI-based histological status prediction in breast cancer. A dataset of 167 patients with invasive ductal carcinoma (IDC) was assembled, consisting of 72 low/intermediate-grade and 95 high-grade cases with preoperative DCE-MRI and T2W images. The data cohort was separated into development (n = 111) and validation (n = 56) cohorts. Each tumour was segmented in the precontrast and the intermediate and last postcontrast DCE-MR images and was mapped to the tumour in the T2W images. Radiomic features, including texture, morphology, and histogram distribution features in the tumour image, were extracted for those image series. Features from the DCE-MR and T2W images were fused by a canonical correlation analysis (CCA)-based method. The support vector machine (SVM) classifiers were trained and tested on the development and validation cohorts, respectively. SVM-based recursive feature elimination (SVM-RFE) was adopted to identify the optimal features for prediction. The areas under the ROC curves (AUCs) for the T2W images and the DCE-MRI series of precontrast, intermediate and last postcontrast images were 0.750 ± 0.047, 0.749 ± 0.047, and 0.788 ± 0.045, respectively, for the development cohort and 0.715 ± 0.068, 0.704 ± 0.073, and 0.744 ± 0.067, respectively, for the validation cohort. After the CCA-based fusion of features from the DCE-MRI series and T2W images, the AUCs increased to 0.751 ± 0.065, 0.803 ± 0.0600 and 794 ± 0.060 in the validation cohort. Moreover, the method of fusing features between DCE-MRI and T2W images using CCA achieved better performance than the concatenation-based feature fusion or classifier fusion methods. Our results demonstrated that anatomical and functional MR images yield complementary information, and feature fusion of radiomic features by matrix transformation to optimize their correlations produced a classifier with improved performance for predicting the histological grade of IDC.}, } @article {pmid31469471, year = {2019}, author = {Giles, M and Graham, L and Ball, J and Watts, W and King, J and Bantawa, K and Paul, M and Harris, A and Paul O'Brien, A and Parker, V}, title = {Variations in indwelling urinary catheter use in four Australian acute care hospitals.}, journal = {Journal of clinical nursing}, volume = {28}, number = {23-24}, pages = {4572-4581}, doi = {10.1111/jocn.15048}, pmid = {31469471}, issn = {1365-2702}, support = {//NSW Ministry of Health Translational Research/ ; }, mesh = {Aged ; Case-Control Studies ; Catheter-Related Infections/*epidemiology/nursing ; Catheters, Indwelling/*adverse effects ; Cross Infection/epidemiology ; Female ; Humans ; Male ; Middle Aged ; New South Wales/epidemiology ; Surveys and Questionnaires ; Time Factors ; Urinary Catheterization/nursing/*statistics & numerical data ; Urinary Catheters ; Urinary Tract Infections/*epidemiology/nursing ; }, abstract = {AIMS AND OBJECTIVES: To identify the point prevalence of indwelling urinary catheters (IDCs) in adult inpatients in acute care hospitals, and to describe the indications for IDC insertion based on patient age, gender, specialty and hospital.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are preventable healthcare-associated infections. IDC duration is the strongest predictor of CAUTI, and little is known about characteristics of patients who receive an IDC.

DESIGN: Two single-day point prevalence surveys collected baseline patient data as part of a larger pre-post control-intervention study.

METHODS: Surveys were conducted at four acute care hospitals in NSW, Australia, for all adult patients. Data collection included IDC presence, insertion details and urine culture collection. Point prevalence data were linked with electronically extracted patient demographic data. This study is presented in line with STROBE checklist (See Supplementary File 1).

RESULT: Data from 1,630 patients were analysed, with 196 patients (12%) identified as having an IDC on the survey dates. IDC prevalence rates were higher in males (13%) than in females (11%). Critical care had the highest rate of patients with IDCs (42%). Urine cultures were collected in 70 patients with an IDC (43%).

CONCLUSIONS: Findings indicated similar rates of IDC use in males and females, and there was no significant difference in age between patients with or without an IDC. However, indication for IDC varied by patient age and gender. High rates of urine culture collection may represent routine collection.

IDC use is found across genders, all age groups and specialties. Nurses should be aware that any of their patients may have an IDC and be particularly aware of certain indications based on patient age and gender. Routine urine culture collection is not advised, and instead, nurses should be guided by clinical decision-making tools.}, } @article {pmid31467444, year = {2020}, author = {Sarhan, MS and Mourad, EF and Nemr, RA and Abdelfadeel, MR and Daanaa, HA and Youssef, HH and Goda, HA and Hamza, MA and Fayez, M and Eichler-Löbermann, B and Ruppel, S and Hegazi, NA}, title = {An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.}, journal = {The Journal of antibiotics}, volume = {73}, number = {1}, pages = {66-71}, pmid = {31467444}, issn = {1881-1469}, mesh = {Actinobacteria/*chemistry ; Bacteriological Techniques ; Colony Count, Microbial ; Culture Media ; Endophytes/*chemistry ; *Microbiota ; Plant Roots/microbiology ; Plant Shoots/microbiology ; Plants/microbiology ; }, abstract = {The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.}, } @article {pmid31456094, year = {2019}, author = {Mamtani, A and Zabor, EC and Rosenberger, LH and Stempel, M and Gemignani, ML and Morrow, M}, title = {Was Reexcision Less Frequent for Patients with Lobular Breast Cancer After Publication of the SSO-ASTRO Margin Guidelines?.}, journal = {Annals of surgical oncology}, volume = {26}, number = {12}, pages = {3856-3862}, pmid = {31456094}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy/*standards ; Mastectomy, Segmental/*standards ; Middle Aged ; Practice Guidelines as Topic/*standards ; Prognosis ; Prospective Studies ; Reoperation/*statistics & numerical data ; }, abstract = {BACKGROUND: The Society of Surgical Oncology and American Society for Radiation Oncology consensus guidelines defined a negative margin for breast-conserving surgery (BCS) as no ink on tumor, and implementation has reduced rates of additional surgery for patients with invasive ductal cancer (IDC). The outcomes for invasive lobular cancer (ILC) patients are uncertain.

METHODS: This study identified patients who had stage 1 or 2 ILC treated with BCS from January 2010 to February 2018. The guidelines were adopted 1 January 2014. Clinicopathologic characteristics, margin status, and reexcisions were compared before and after adoption of the guidelines and with those of IDC patients treated from May 2013 to February 2015.

RESULTS: Among 745 early-stage ILC patients undergoing BCT, 312 (42%) were treated before the guidelines and 433 (58%) after the guidelines. Most clinicopathologic characteristics were similar between the two groups, with differences in lobular carcinoma in situ, lymphovascular invasion, and node-positivity rates. The overall rates of additional surgery declined significantly after the guidelines (31.4 to 23.1%; p = 0.01), but the difference did not reach significance for reexcisions (19.9 to 15.2%; p = 0.12) or conversions to mastectomy (11.5 to 7.9%; p = 0.099) individually. Between eras, no difference in incidence or number of tumor on ink or ≤ 2 mm margins was observed (all p = 0.2). Larger tumors, younger age, and pre-guideline era were independently associated with additional surgery. Only younger age was predictive of mastectomy. Among 431 pre-guideline and 601 post-guideline IDC patients, reexcisions declined from 21.3 to 14.8% (p = 0.008), and conversion to mastectomy was rare (0.6%). The magnitude of reduction in any additional surgery (interaction, p = 0.92) and reexcisions (interaction, p = 0.56) was similar between ILC and IDC.

CONCLUSIONS: Despite differences in growth pattern and conspicuity, guideline adoption significantly reduced additional surgery among ILC patients, with a magnitude of benefit similar to that among IDC patients.}, } @article {pmid31452673, year = {2019}, author = {Dobbels, AA and Lorenz, AJ}, title = {Soybean iron deficiency chlorosis high throughput phenotyping using an unmanned aircraft system.}, journal = {Plant methods}, volume = {15}, number = {}, pages = {97}, pmid = {31452673}, issn = {1746-4811}, abstract = {BACKGROUND: Iron deficiency chlorosis (IDC) is an abiotic stress in soybean [Glycine max (L.) Merr.] that causes significant yield reductions. Symptoms of IDC include interveinal chlorosis and stunting of the plant. While there are management practices that can overcome these drastic yield losses, the preferred way to manage IDC is growing tolerant soybean varieties. To develop varieties tolerant to IDC, breeders may easily phenotype up to thousands of candidate soybean lines every year for severity of symptoms related to IDC, a task traditionally done with a 1-5 visual rating scale. The visual rating scale is subjective and, because it is time consuming and laborious, can typically only be accomplished once or twice during a growing season.

RESULTS: The goal of this study was to use an unmanned aircraft system (UAS) to improve field screening for tolerance to soybean IDC. During the summer of 2017, 3386 plots were visually scored for IDC stress on two different dates. In addition, images were captured with a DJI Inspire 1 platform equipped with a modified dual camera system which simultaneously captures digital red, green, blue images as well as red, green, near infrared (NIR) images. A pipeline was created for image capture, orthomosaic generation, processing, and analysis. Plant and soil classification was achieved using unsupervised classification resulting in 95% overall classification accuracy. Within the plant classified canopy, the green, yellow, and brown plant pixels were classified and used as features for random forest and neural network models. Overall, the random forest and neural network models achieved similar misclassification rates and classification accuracy, which ranged from 68 to 77% across rating dates. All 36 trials in the field were analyzed using a linear model for both visual score and UAS predicted values on both dates. In 32 of the 36 tests on date 1 and 33 of 36 trials on date 2, the LSD associated with UAS image-based IDC scores was lower than the LSD associated with visual scores, indicating the image-based scores provided more precise measurements of IDC severity.

CONCLUSIONS: Overall, the UAS was able to capture differences in IDC stress and may be used for evaluations of candidate breeding lines in a soybean breeding program. This system was both more efficient and precise than traditional scoring methods.}, } @article {pmid31448509, year = {2020}, author = {Nomikos, A and Husain, EA and Graham, AD}, title = {Occult disease in reduction mammoplasties and prophylactic mastectomies.}, journal = {The breast journal}, volume = {26}, number = {4}, pages = {691-696}, doi = {10.1111/tbj.13512}, pmid = {31448509}, issn = {1524-4741}, mesh = {*Breast Neoplasms/epidemiology/prevention & control/surgery ; Female ; Humans ; *Mammaplasty ; Mastectomy ; *Prophylactic Mastectomy ; Retrospective Studies ; }, abstract = {The aim of this study was to determine the incidence of occult breast carcinoma and significant breast disease in clinically and radiologically unremarkable breast reduction specimens and prophylactic mastectomies. A retrospective search using specimen type codes was performed in the computerized histopathology archive from April 2007 to April 2016. The pathology results of 505 patients were analyzed (782 specimens). A total of 267 patients underwent simple reduction mammoplasties (10 unilateral), 20 had bilateral prophylactic mastectomies and 218 undertook contralateral symmetrizing or prophylactic mastectomy surgery following a history of breast cancer. Overall, normal (unremarkable) breast tissue was found in 42.6% of patients (n = 215), benign tissue (nonproliferative/proliferative disease without atypia) in 51.1% (n = 258), significant disease (LCIS/proliferative disease with atypia) in 5.5% (n = 28), and malignant disease (invasive/ductal carcinoma in situ) in 0.8% (n = 4). The incidence of significant breast pathology was statistically higher (P value < .0001) in prophylactic mastectomies (12.4%) compared to reduction mammoplasties (2.3%). There was however no significant increase in the incidence of malignancy between prophylactic mastectomies (1.2%) and reduction mammoplasties (0.6%). Even though the clear majority of resected tissue in reduction mammoplasties and prophylactic mastectomies is benign, our findings support the continued need for histological examination of these specimens for occult carcinoma and precursor lesions.}, } @article {pmid31443882, year = {2019}, author = {Sadeh-Sharvit, S}, title = {Use of Technology in the Assessment and Treatment of Eating Disorders in Youth.}, journal = {Child and adolescent psychiatric clinics of North America}, volume = {28}, number = {4}, pages = {653-661}, doi = {10.1016/j.chc.2019.05.011}, pmid = {31443882}, issn = {1558-0490}, mesh = {Adolescent ; Feeding and Eating Disorders/*diagnosis/*therapy ; Humans ; *Mobile Applications ; Patient Acceptance of Health Care ; *Self Care ; *Smartphone ; Telemedicine ; }, abstract = {For countless young people, technology plays an essential role in their lives. However, its many advantages have not yet been widely applied to the treatment of youth with eating disorders. This article looks at how smartphone applications, Web conferencing, and other developments could widen the range of care available in a field where suitable support can be hard to find. Various barriers to treatment exist, such as cost, access, and the stigma attached to eating disorders, but existing and new technologies could overcome those obstacles, if clinicians are willing and able to meet the requirements associated with digitally enhanced treatment.}, } @article {pmid31442306, year = {2020}, author = {Lahat, E and Mikulincer, M and Lifshin, U and Shaver, PR}, title = {Mothers never retire: Contextual priming of working models of mother affects adults' representations of self and romantic partners.}, journal = {Journal of personality}, volume = {88}, number = {3}, pages = {501-514}, doi = {10.1111/jopy.12506}, pmid = {31442306}, issn = {1467-6494}, mesh = {Adult ; Female ; Humans ; Male ; Mothers/*psychology ; Personality/*physiology ; *Self Concept ; Sexual Partners/*psychology ; *Social Perception ; Young Adult ; }, abstract = {OBJECTIVES: The main goal of these studies is to provide an experimental test of a core hypothesis based on attachment theory: Working models of mother are active in adults' minds and can bias their views of self and romantic partners.

METHOD: In two studies, we conducted clinical interviews to identify positive and negative core traits that participants used to describe their mothers. We then implicitly primed either positive or negative traits extracted from the interviews and compared this priming condition to control conditions in which we primed either positive or negative control traits (traits that described the mother of another study participant). Following this manipulation, we assessed participants' self-appraisals (Study 1) and explanations of their romantic partner's hurtful behaviors (Study 2).

RESULTS: Priming with one's mother's positive traits led to more positive views of self and romantic partner (compared with the effects of priming with positive control traits). In contrast, as compared to negative control traits, the priming of one's mother's negative traits led to less positive views of self and romantic partner.

CONCLUSIONS: Findings support the hypothesis that working models of mother play a causal role in shaping adults' representations of self and romantic partners.}, } @article {pmid31440248, year = {2019}, author = {Escoter-Torres, L and Caratti, G and Mechtidou, A and Tuckermann, J and Uhlenhaut, NH and Vettorazzi, S}, title = {Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1859}, pmid = {31440248}, issn = {1664-3224}, mesh = {Animals ; Gene Expression Regulation/*drug effects/*immunology ; Glucocorticoids/*immunology/pharmacology ; Humans ; Immunosuppressive Agents/*immunology/pharmacology ; Receptors, Glucocorticoid/*immunology ; }, abstract = {For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.}, } @article {pmid31439369, year = {2020}, author = {van Leenders, GJLH and Kweldam, CF and Hollemans, E and Kümmerlin, IP and Nieboer, D and Verhoef, EI and Remmers, S and Incrocci, L and Bangma, CH and van der Kwast, TH and Roobol, MJ}, title = {Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups.}, journal = {European urology}, volume = {77}, number = {2}, pages = {191-198}, doi = {10.1016/j.eururo.2019.07.051}, pmid = {31439369}, issn = {1873-7560}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/*pathology/therapy ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prostate/*pathology ; Prostatic Neoplasms/*pathology/therapy ; }, abstract = {BACKGROUND: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use.

OBJECTIVE: To perform a proof-of-principle study incorporating CR/IDC in the current GG.

All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent.

INTERVENTION: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient. Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic.

RESULTS AND LIMITATIONS: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study.

CONCLUSIONS: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca.

PATIENT SUMMARY: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.}, } @article {pmid31437176, year = {2019}, author = {Santos Junior, OR and da Costa Rocha, MO and Rodrigues de Almeida, F and Sales da Cunha, PF and Souza, SCS and Saad, GP and Santos, TADQ and Ferreira, AM and Tan, TC and Nunes, MCP}, title = {Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.}, journal = {PloS one}, volume = {14}, number = {8}, pages = {e0221028}, pmid = {31437176}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology ; Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology ; Heart Transplantation/statistics & numerical data ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Prognosis ; Stroke Volume/physiology ; Survival Analysis ; Ventricular Function, Left/physiology ; }, abstract = {BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.

OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.

METHODS: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.

RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).

CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.}, } @article {pmid31436745, year = {2019}, author = {Korzets, Y and Lee, G and Espin-Garcia, O and Purdie, T and Koch, AC and Hodgson, D and Barry, A and Fyles, A}, title = {The Role of Partial Breast Radiation in the Previously Radiated Breast.}, journal = {American journal of clinical oncology}, volume = {42}, number = {12}, pages = {932-936}, doi = {10.1097/COC.0000000000000584}, pmid = {31436745}, issn = {1537-453X}, mesh = {Adult ; Aged ; Brachytherapy/*methods/mortality ; Breast Neoplasms/mortality/pathology/*radiotherapy/surgery ; Cancer Care Facilities ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*radiotherapy/surgery ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasm Staging ; Ontario ; *Patient Safety ; Prognosis ; Radiotherapy Dosage ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Assessment ; Role ; Survival Analysis ; Treatment Outcome ; }, abstract = {OBJECTIVES: The aim of this study was to analyze breast cancer patients who previously had mantle-field or breast radiation (RT) followed by retreatment with external beam partial breast irradiation (EB PBI).

MATERIALS AND METHODS: We retrospectively reviewed all women with newly diagnosed early-stage breast cancer treated with lumpectomy and partial breast irradiation between 2007 and 2017 who had undergone prior chest or breast RT.

RESULTS: Of 11 patients recorded, 8 (73%) had Hodgkin lymphoma, and 3 (27%) had ipsilateral breast cancer diagnosis. Median age at initial and second diagnosis was 28 and 48 years, respectively. The lymphoma patients received a dose of 35 Gy in 16 to 20 fractions to a classic mantle-upper abdomen field. Patients with an initial diagnosis of breast cancer received whole-breast RT (2 with 50 Gy/25 fractions, 1 with 40 Gy in 16 fractions). Median time from initial to second diagnosis was 22.6 years (range, 13.5 to 32.6 y). All had early-stage (I to II) invasive ductal carcinoma and were treated with lumpectomy or repeat lumpectomy and EB PBI. Four received a dose of 45 Gy/25 fractions, 4 to 50 Gy/25 fractions, and 3 to 42.4 Gy/16 fractions. All patients received adjuvant systemic treatment. Two patients had toxicity, 1 had grade 1 induration, and the other had grade 2 fat atrophy and grade 1 fibrosis. One patient developed a contralateral breast cancer. No locoregional recurrences were reported at the median follow-up of 4.6 years (range, 0.6 to 10.5 y).

CONCLUSION: EB PBI after lumpectomy seems to be a safe and effective RT treatment option for selected patients with prior RT and localized early-stage breast cancer.}, } @article {pmid31436245, year = {2019}, author = {Zhao, S and Shao, G and Chen, P and Li, L and Yang, Y and Zhao, X and Guo, W}, title = {Diagnostic performance of minimum apparent diffusion coefficient value in differentiating the invasive breast cancer and ductal carcinoma in situ.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {4}, pages = {871-875}, doi = {10.4103/jcrt.JCRT_607_18}, pmid = {31436245}, issn = {1998-4138}, mesh = {Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Follow-Up Studies ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: This study is to explore the role of the minimum apparent diffusion coefficient (ADC-min) value in the diagnosis of invasive breast cancer and ductal carcinoma in situ (DCIS).

MATERIALS AND METHODS: A total of 196 breast cancer patients with pathologically verified lesions were included. They received diffusion-weighted imaging and dynamic breast magnetic resonance imaging before the pathological confirmation. The ADC-min value and its relationship with invasive ductal carcinoma (IDC), IDC-DCIS, and DCIS were analyzed.

RESULTS: Of the 196 breast cancer patients, there were 115 (58.67%) cases of IDC, 53 (27.04%) cases of IDC-DCIS, and 28 (14.29%) cases of DCIS. The mean ADC-min values for IDC, IDC-DCIS, and DCIS were (0.96 ± 0.16) × 10[-3], (1.10 ± 0.13) × 10[-3], and (1.24 ± 0.17) × 10[-3] mm [2]/s, respectively. The mean ADC-min value of IDC was significantly lower than that of IDC-DCIS and that of IDC-DCIS was significantly lower than that of DCIS (P < 0.01). The mean ADC-min value was also significantly different between invasive cancer and DCIS (P < 0.01). The mean ADC-min value can be used in the differential diagnosis of DCIS, with a cutoff point of 1.02 × 10[-3] mm [2]/s (sensitivity of 92.9% and specificity of 57.7%).

CONCLUSIONS: The ADC-min values are significantly different among IDC, IDC-DCIS, and DCIS, with the lowest ADC-min values in IDC, followed by IDC-DCIS and DCIS. The ADC-min maybe used as a promising parameter to differentiate DCIS and invasive cancer.}, } @article {pmid31434424, year = {2019}, author = {Cheng, X and Yu, RS and Xu, M and Wu, XL and Chen, CM and Liu, WW and Ji, JS}, title = {[The correlation between functional magnetic resonance imaging features and expression of Her-2 in breast cancer].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {31}, pages = {2440-2444}, doi = {10.3760/cma.j.issn.0376-2491.2019.31.007}, pmid = {31434424}, issn = {0376-2491}, support = {2016KYA201//Zhejiang Pharmaceutical and Health Science and Technology Program General Project/ ; }, mesh = {*Breast Neoplasms/diagnostic imaging ; Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; Receptor, ErbB-2 ; Retrospective Studies ; }, abstract = {Objective: To explore the correlation between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance diffusion-weighted imaging (DWI) images of breast cancer and human epidermal growth factor receptor-2 (Her-2) expression. Methods: A retrospective analysis of 84 patients with breast cancer confirmed by biopsy from January 2012 to December 2016 in Zhejiang University Lishui Hospital was conducted. The data of DCE-MRI, DWI scanning were collected before surgery and Her-2 was detected by immunohistochemistry (IHC). Then, all the patients were divided into Her-2 positive group and Her-2 negative group according to Her-2 expression. There were 44 cases in the Her-2 positive group and 40 cases in the Her-2 negative group. The differences in the characteristics of the lesion morphology, time-signal intensity curve (TIC), early enhancement rate and apparent diffusion coefficient (ADC) were compared, and their correlation with Her-2 expression was analyzed. Results: Of the 84 lesions, 12 were orthotopic ductal carcinoma, 6 were lobular carcinoma, and 66 were invasive ductal carcinoma. There were significant differences in lesion morphology (P=0.012) and TIC curve morphology (P=0.038) between Her-2 positive group and negative group. At the same time, the early enhancement rate (P=0.012) and ADC value (P=0.038) of Her-2 positive group were significantly higher than those of negative group. Except morphology of segmental lesions and TIC curve morphology, other characteristic parameters were correlated to Her-2 (all P<0.05). The correlation coefficients between early enhancement rate, ADC value and Her-2 expression were as high as 0.758 and 0.809 (all P<0.05). Conclusions: The morphology of breast cancer lesions, time-signal intensity curve, early enhancement rate and ADC value are all correlated with Her-2 expression.The early enhancement rate and ADC value are significantly positively correlated with Her-2 expression.}, } @article {pmid31431782, year = {2019}, author = {Yetkin, G and Celayir, MF and Tanik, C and Citgez, B and Uludag, M and Mihmanli, M}, title = {Male breast cancer: A 10 year retrospective case series in a tertiary care hospital.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {69}, number = {8}, pages = {1209-1212}, pmid = {31431782}, issn = {0030-9982}, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Axilla ; Breast Neoplasms, Male/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Male ; Mastectomy ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Survival Rate ; Tertiary Care Centers ; Tumor Burden ; Turkey ; }, abstract = {Male breast cancer is a rare disease and it differs from breast cancer in women by some characteristics. The incidence of the disease has increased in the last 25 years. The records of male patients who underwent surgery for breast cancer between 2007 and 2017 were retrospectively reviewed in a tertiary care hospital in Istanbul, Turkey. The patients' ages, background, family history, clinical features, histopathological features of the tumour, its stage, the treatment and the survival were investigated. SPSS 15.0 for Windows programme was used for statistical analysis.Survival analysis was performed with Kaplan-Meier method.Determinants were analysed by univariate Cox regression analysis. A total of 15 patients were evaluated in our study. Fourteen patients had invasive ductal carcinoma and one patient had intraductal papillary carcinoma. The median followup period of the patients was 36 months The axillary lymph node metastasis positivity rate (number of metastatic lymph nodes/number of lymph nodes dissected) was statistically significantly higher in patients who died than in patients who survived.In univariate Cox regression analysis, the effects of age, tumour size, estrogen, progesterone, the presence of HER2/neu receptor and axillary metastasis on survival were not determined. We believe that raising awareness on male breast cancer in the community, genetic testing and screening mammography in high-risk patients will be useful in early diagnosis of the disease and improvement of its prognosis.}, } @article {pmid31430229, year = {2021}, author = {Shenkman, G and Stein, Y and Bos, H}, title = {The Mediating Role of Attachment Avoidance in the Association between Sexual Orientation and Mental Health.}, journal = {Journal of homosexuality}, volume = {68}, number = {3}, pages = {461-475}, doi = {10.1080/00918369.2019.1656507}, pmid = {31430229}, issn = {1540-3602}, mesh = {Adolescent ; Adult ; Aged ; Anxiety/psychology ; Female ; Heterosexuality/psychology ; Homosexuality/*psychology ; Humans ; Male ; *Mental Health ; Middle Aged ; *Object Attachment ; Sexual and Gender Minorities/psychology ; Young Adult ; }, abstract = {The current study examined whether attachment avoidance mediates the association between being a sexual minority (gay men or lesbian women) and poorer mental health outcomes. For this purpose a community-dwelling sample of 350 gay men and lesbian women (M = 30.39, SD = 6.82) and 445 heterosexual men and women (M = 26.95, SD = 3.11) completed measures of attachment avoidance, depressive symptoms, anxiety symptoms and life satisfaction. Results showed that gay men and lesbians reported poorer mental health. Moreover, attachment avoidance had a mediating effect on the association between being a sexual minority and depressive symptoms, anxiety symptoms and life satisfaction. These findings are some of the first to suggest empirical support for the role of attachment avoidance in accounting for the mental health vulnerability of gay men and lesbians. The results contribute to a better understanding of the minority stress model and should be addressed by practitioners.}, } @article {pmid31428741, year = {2019}, author = {Vaughan, K and Ozaltin, A and Mallow, M and Moi, F and Wilkason, C and Stone, J and Brenzel, L}, title = {The costs of delivering vaccines in low- and middle-income countries: Findings from a systematic review.}, journal = {Vaccine: X}, volume = {2}, number = {}, pages = {100034}, pmid = {31428741}, issn = {2590-1362}, abstract = {INTRODUCTION: Information on immunization delivery costs (IDCs) is essential for better planning and budgeting for the sustainability and performance of national programs. However, delivery cost evidence is fragmented and of variable quality, making it difficult for policymakers, planners, and other stakeholders to understand and use. This study aimed to consolidate and summarize the evidence on delivery costs, answering the question: What are the unit costs of vaccine delivery across low- and middle-income countries (LMICs) and through a variety of delivery strategies?

METHODS: We conducted a systematic review of over 15,000 published and unpublished resources from 2005 to 2018 that included IDCs in LMICs. We quality-rated and extracted data from 61 resources that contained 410 immunization delivery unit costs (e.g., cost per dose, cost per fully immunized child). We converted cost findings to a common year (2016) and currency (U.S. dollars) to ensure comparability across studies and settings. We performed a descriptive and gap analysis and developed immunization delivery cost ranges using comparable unit costs for single vaccines and schedules of vaccines.

RESULTS: The majority of IDC evidence comes from low-income countries and Sub-Saharan Africa. Most unit costs are presented as cost per dose and represent health facility-based delivery.

DISCUSSION: The cost ranges may be higher than current estimates used in many LMICs for budgeting: $0.16-$2.54 incremental cost per dose (including economic, financial, and fiscal costs) for single, newly introduced vaccines, and $0.75-$9.45 full cost per dose (economic costs) for schedules of four to eight vaccines delivered to children under one.

CONCLUSIONS: Despite increased attention on improving coverage and strengthening immunization delivery, evidence on the cost of delivery is nascent but growing. The cost ranges can inform planning and policymaking, but should be used with caution given their width and the few unit costs used in their development.}, } @article {pmid31427562, year = {2019}, author = {Sun, Y and Lei, B and Huang, Q}, title = {SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {25}, number = {}, pages = {6244-6254}, pmid = {31427562}, issn = {1643-3750}, mesh = {Adenylate Kinase/*metabolism ; Apoptosis/physiology ; Carcinoma, Hepatocellular/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/genetics/*metabolism/*pathology ; Neoplasm Invasiveness ; SOXF Transcription Factors/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.}, } @article {pmid31427558, year = {2019}, author = {Lin, SC and Ko, RT and Kang, BH and Wang, JS}, title = {Intraductal Carcinoma of Salivary Gland Originating from an Intraparotid Lymph Node: A Case Report.}, journal = {The Malaysian journal of pathology}, volume = {41}, number = {2}, pages = {207-211}, pmid = {31427558}, issn = {0126-8635}, mesh = {Aged, 80 and over ; Carcinoma, Ductal/*pathology ; Humans ; Lymph Nodes/*pathology ; Male ; Parotid Neoplasms/*pathology ; }, abstract = {INTRODUCTION: Salivary gland intraductal carcinoma (IDC) is rare. We present the second case of IDC originating from an intraparotid lymph node (LN) with a more detailed description of the histogenesis, immunohistochemistry (IHC) and updated molecular information.

CASE REPORT: An 87-year-old male had a tumour nodule over the left parotid tail for about 20 years. Physical examinations revealed a 4.5 cm soft, non-tender and fixed mass. After the left parotidectomy, pathology confirmed the diagnosis of IDC arising within an intraparotid lymph node. The cystic component of the tumour was lined by single to multilayered ductal cells with micropapillary growth pattern. The solid part showed intraductal proliferation of neoplastic cells in solid, cribriform, micropapillary and Roman bridge-like structure. By immunohistochemistry (IHC), the tumour cells were positive for S-100, CK (AE1/AE3), mammaglobin, SOX10, and estrogen receptor (ER), with myoepithelial cell rimming highlighted by positive p63 and calponin IHC stains. The prognosis of this patient is excellent after complete excision.

DISCUSSION: The mechanism of salivary gland tumour arising in the intra-parotid gland LN was assumed to be related to salivary duct inclusion within the intraparotid gland LN which is a normal occurrence during embryology development. Although the terminology may raise some confusion about the relationship between IDC and conventional salivary duct carcinoma (SDA), they are different in immunophenotype and clinicopathologic features. IDC is characterised by S100 (+) ER (+) with predominant intraductal growth and excellent prognosis; while SDC features S100 (-) androgen receptor (+) with predominant invasive growth and aggressive behavior. Recent discovery of recurrent RET gene rearrangement in IDC but not SDC also supports that IDC is not precursor lesion of the SDC.}, } @article {pmid31424026, year = {2020}, author = {Chen, JR and Zhao, JG and Zhu, S and Zhang, MN and Chen, N and Liu, JD and Sun, GX and Shen, PF and Zeng, H}, title = {Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.}, journal = {Asian journal of andrology}, volume = {22}, number = {4}, pages = {427-431}, pmid = {31424026}, issn = {1745-7262}, mesh = {Abiraterone Acetate/therapeutic use ; Adenocarcinoma/metabolism/*secondary/therapy ; Aged ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Biopsy, Large-Core Needle ; Bone Neoplasms/metabolism/*secondary/therapy ; Docetaxel/therapeutic use ; Functional Status ; Humans ; Kaplan-Meier Estimate ; Male ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neuroendocrine Tumors ; Orchiectomy ; Prognosis ; Progression-Free Survival ; Proportional Hazards Models ; Prostate-Specific Antigen/metabolism ; Prostatectomy ; Prostatic Neoplasms/metabolism/*pathology/therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism/pathology/therapy ; Retrospective Studies ; Survival Rate ; }, abstract = {This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan-Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml[-1], had worse prognoses if EPE was detected. In patients with PSA <50 ng ml[-1], EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218-14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.}, } @article {pmid31423399, year = {2019}, author = {Maciolek, LM and Harmon, TS and He, J and Sadruddin, S and Nguyen, QD}, title = {Pseudoangiomatous Stromal Hyperplasia of the Breast: A Rare Finding in a Male Patient.}, journal = {Cureus}, volume = {11}, number = {6}, pages = {e4923}, pmid = {31423399}, issn = {2168-8184}, abstract = {Pseudoangiomatous stromal hyperplasia (PASH) in male patients is a rare condition that represents a hormonally-induced proliferation of mesenchymal tissue of the breast. This benign pathology is often undiagnosed due to many reasons. When PASH presents as a breast mass, it appears innocent, developing as a smooth and well-circumscribed tumor. Furthermore, it does not elicit suspicious findings on imaging. These points often halt further investigation of many breast abnormalities. Breast masses are statistically most likely to be gynecomastia when they arise in men. However, they are important to investigate because, although rare, breast cancer can occur in men. Furthermore, the benign conditions of the breast that commonly affect women can also impact male patients. It is oftentimes overlooked that men too can experience hormonal stimulation of the breast tissue. The following case describes this rare but important instance of a male patient diagnosed with PASH following a previous diagnosis of infiltrative ductal carcinoma in situ of the contralateral breast.}, } @article {pmid31418311, year = {2020}, author = {Cohen, OBS and Shahar, G and Brunstein Klomek, A}, title = {Peer Victimization, Coping Strategies, Depression, and Suicidal Ideation Among Young Adolescents.}, journal = {Crisis}, volume = {41}, number = {3}, pages = {156-162}, doi = {10.1027/0227-5910/a000614}, pmid = {31418311}, issn = {2151-2396}, mesh = {*Adaptation, Psychological ; Adolescent ; Aggression ; Bullying/psychology/*statistics & numerical data ; Child ; Crime Victims/psychology/statistics & numerical data ; Cross-Sectional Studies ; Depression/*epidemiology/psychology ; Female ; Humans ; Israel/epidemiology ; Linear Models ; Logistic Models ; Male ; *Peer Group ; Self Report ; *Suicidal Ideation ; }, abstract = {Background: Victimization by bullying among adolescents is a widespread phenomenon associated with depression and suicidal ideation. Coping with bullying may include aggressive responding and self-blame. Aims: The purpose of this study was to examine the role adolescent self-blame and aggression - representing coping with peer bullying - in depression and suicide ideation. Method: We recruited 97 "pure" victims (41 girls; mean age = 12.69, SD = .80) identified from a sample of 505 adolescents (242 girls; mean age = 12.73, SD = .81) from two Israeli high schools. Self-report questionnaires were used to assess victimization, aggressive responses, self-blame, depression, and suicide ideation. Results: Self-blame in the face of peer bullying was uniquely associated with both depression and suicide ideation. The effect was robust even after controlling for level of victimization. No direct effect of aggressive coping or moderating effects of self-blame or aggression on the association between victimization and depression/suicide ideation were found. Limitations: This study used a cross-sectional design and made exclusive use of self-report measures. Conclusion: Adolescents who blame themselves for being bullied might be at a heightened risk for depression and suicidality compared to adolescents who did not use self-blame.}, } @article {pmid31417064, year = {2019}, author = {Bozkurt, H and Karakaya, IB and Aktas, E and Irkorucu, O}, title = {Coexistence of phylloides tumour and invasive ductal cancer in the breast.}, journal = {Nigerian journal of clinical practice}, volume = {22}, number = {8}, pages = {1169-1171}, doi = {10.4103/njcp.njcp_602_18}, pmid = {31417064}, issn = {1119-3077}, mesh = {Adult ; Biopsy ; Breast/*diagnostic imaging ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Mammography ; Phyllodes Tumor/*pathology/surgery ; Treatment Outcome ; Ultrasonography, Mammary ; }, abstract = {Phylloides tumor in the breast is a rare fibroepithelial tumor, which is often seen in young adult women. Phylloides tumor of the breast accounts for about 1% of all breast tumors and approximately 3% of all fibroepithelial tumors. Pre-operative diagnosis is difficult. Since there aren't any specific mammography and ultrasound findings, they cannot be distinguished from fibroadenomas through these imaging methods and are mostly followed up as if they are fibroadenomas. Patients often present with the complaint of a mass that has been present for a long time and had started to grow suddenly. The primary preferred approach for treatment is wide local excision with negative surgical margins. Coexistence of invasive ductal carcinoma with phylloides tumor in the same breast is a very rare occurrence. We present in this article, a 42-year-old female patient with an invasive ductal carcinoma inside a phylloides tumor in the same breast.}, } @article {pmid31411354, year = {2019}, author = {Balbinot, EDCA and Pereira, MFCC and Skupien, JA and Balbinot, CEA and da Rocha, G and Vieira, S}, title = {Analysis of transmittance and degree of conversion of composite resins.}, journal = {Microscopy research and technique}, volume = {82}, number = {11}, pages = {1953-1961}, doi = {10.1002/jemt.23364}, pmid = {31411354}, issn = {1097-0029}, mesh = {Composite Resins/*chemistry ; Materials Testing/*methods ; Spectroscopy, Fourier Transform Infrared ; Surface Properties ; }, abstract = {The objective of this study was to evaluate and correlate light transmittance (T), initial degree of conversion (IDC), and degree of conversion after 24 hr (DC24) for 22 composite resins (CR) for enamel and dentin use. The transmittance (n = 10) was measured with a spectrometer at a wavelength of 468.14 nm. The degree of conversion (DC; n = 5) was measured with Fourier Transform Near-Infrared Spectroscopy before polymerization, immediately after photoactivation, and 24 hr after photoactivation. Both sets of values are provided as percentages. ANOVA and Games-Howell (α = 5%) tests showed that Filtek Supreme Ultra gave the highest T values of all enamel CRs, while Esthet-X HD presented the lowest. Meanwhile, Venus diamond gave the highest values of all dentin CRs, while Esthet-X HD gave the lowest. For IDC and DC24, ANOVA showed differences between individual CRs and the two CR types (p < .0001). Despite the limitations of this study, it can be concluded that there was no correlation between T and either IDC or DC24 (p > .05); however, IDC and DC24 were strongly correlated (p < .05) by Pearson's correlation. That being said, as a higher DC reflects better mechanical properties, certain conclusions can be drawn about overall performance. The best IDC values were observed for the Opallis enamel resin and the Opallis and Premise dentin resins. Meanwhile, the best DC24 values were observed for the Opallis, Charisma, and Premise enamel resins and the Opallis and Premise dentin resins. Degree of conversion and light transmittance showed differences between composite resin types (enamel and dentin) and brands. It is important to know at the moment of composite choice taking into account mechanical and optical properties.}, } @article {pmid31409615, year = {2019}, author = {Walsh, L and Haley, KE and Moran, B and Mooney, B and Tarrant, F and Madden, SF and Di Grande, A and Fan, Y and Das, S and Rueda, OM and Dowling, CM and Varešlija, D and Chin, SF and Linn, S and Young, LS and Jirström, K and Crown, JP and Bernards, R and Caldas, C and Gallagher, WM and O'Connor, DP and Ní Chonghaile, T}, title = {BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {23}, pages = {7139-7150}, doi = {10.1158/1078-0432.CCR-19-0713}, pmid = {31409615}, issn = {1557-3265}, support = {202079/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aniline Compounds/*pharmacology ; Antineoplastic Agents/*pharmacology ; Apoptosis ; Azepines/*pharmacology ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Lobular/*drug therapy/metabolism/pathology ; Cell Cycle ; Cell Proliferation ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sulfonamides/*pharmacology ; Survival Rate ; Transcription Factors/*antagonists & inhibitors ; Triazoles/*pharmacology ; Tumor Cells, Cultured ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in estrogen receptor-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extraterminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.

EXPERIMENTAL DESIGN: We assessed whether targeting the BET proteins with JQ1 could serve as an effective therapeutic strategy in ILC in both 2D and 3D models. We used dynamic BH3 profiling and RNA-sequencing (RNA-seq) to identify transcriptional reprograming enabling resistance to JQ1-induced apoptosis. As part of the RATHER study, we obtained copy-number alterations and RNA-seq on 61 ILC patient samples.

RESULTS: Certain ILC cell lines were sensitive to JQ1, while others were intrinsically resistant to JQ1-induced apoptosis. JQ1 treatment led to an enhanced dependence on antiapoptotic proteins and a transcriptional rewiring inducing fibroblast growth factor receptor 1 (FGFR1). This increase in FGFR1 was also evident in invasive ductal carcinoma (IDC) cell lines. The combination of JQ1 and FGFR1 inhibitors was highly effective at inhibiting growth in both 2D and 3D models of ILC and IDC. Interestingly, we found in the RATHER cohort of 61 ILC patients that 20% had FGFR1 amplification and we showed that high BRD3 mRNA expression was associated with poor survival specifically in ILC.

CONCLUSIONS: We provide evidence that BETi either alone or in combination with FGFR1 inhibitors or BH3 mimetics may be a useful therapeutic strategy for recurrent ILC patients.}, } @article {pmid31407990, year = {2019}, author = {Cernadas Curotto, P and Halperin, E and Sander, D and Klimecki, O}, title = {Emotions in attacker-defender conflicts.}, journal = {The Behavioral and brain sciences}, volume = {42}, number = {}, pages = {e120}, doi = {10.1017/S0140525X19000918}, pmid = {31407990}, issn = {1469-1825}, mesh = {*Emotions ; }, abstract = {The distinction between attackers and defenders might help refine the understanding of the role of emotions in conflicts. Here, we briefly discuss differences between attackers and defenders in terms of appraisals, action tendencies, emotional preferences, and brain activities. Finally, we outline how attackers and defenders may differ in their response to emotion-based interventions that aim to promote conflict resolution.}, } @article {pmid31407561, year = {2019}, author = {Wan, N and Liu, D and Lu, L and He, X and Song, D and Li, Z and Zhou, X and Peng, W and Liu, Z}, title = {[Application of pedicled omentum flap in breast reconstruction of breast cancer patients].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {33}, number = {8}, pages = {1006-1010}, pmid = {31407561}, issn = {1002-1892}, mesh = {Adult ; *Breast Neoplasms ; Female ; Humans ; *Mammaplasty ; Mastectomy ; Neoplasm Recurrence, Local ; Omentum ; }, abstract = {OBJECTIVE: To explore the clinical application of the pedicled omentum flap in breast reconstruction of breast cancer patients.

METHODS: Between May 2013 and October 2017, 205 patients with breast cancer received modified mastectomy. The pedicled omentum flap was used to reconstruct breast at the same time. All patients were female with an average age of 34.9 years (mean, 26-58 years). The tumor located at left breast in 127 cases and right side in 78 cases. The diameter of the tumor was 2-5 cm (mean, 2.9 cm). The 120 cases of breast cancer were at stage Ⅰ and 85 cases were at stage Ⅱ; and 126 cases were invasive ductal carcinoma and 79 cases were invasive lobular carcinoma. The course of disease ranged from 10 to 92 days (mean, 38.5 days). The size of defect after tumor ablation ranged from 9 cm× 6 cm to 18 cm×12 cm; the size of pedicled omentum flap ranged from 18 cm×10 cm to 22 cm×16 cm.

RESULTS: According to the anatomical basis, the omentum was divided into 4 types, including thin type (42 cases, 20.5%), medium type (133 cases, 64.9%), hypertrophy type (24 cases, 11.7%), and absence type (6 cases, 2.9%). All omentum flaps survived successfully and the incisions healed by first intention. All patients were followed up 6-74 months (mean, 24.5 months); 83 cases were followed up more than 5 years. The shape, texture, and elasticity of the reconstructed breast were good and no flap contracture deformation happened. Only linear scar left at the donor sites, and the function of abdomen was not affected. No local recurrence happened.

CONCLUSION: The pedicled omentum flap can be harvested safely and reliable, which is the one of ideal option for breast reconstruction in breast cancer patients.}, } @article {pmid31399195, year = {2019}, author = {Winer, LK and Hinrichs, BH and Lu, S and Hanseman, D and Huang, Y and Reyna, C and Lewis, J and Shaughnessy, EA}, title = {Flat epithelial atypia and the risk of sampling error: Determining the value of excision after image-guided core-needle biopsy.}, journal = {American journal of surgery}, volume = {218}, number = {4}, pages = {730-736}, doi = {10.1016/j.amjsurg.2019.07.020}, pmid = {31399195}, issn = {1879-1883}, mesh = {*Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Epithelial Cells/*pathology ; Female ; Humans ; Hyperplasia ; *Image-Guided Biopsy ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Selection Bias ; }, abstract = {BACKGROUND: We determined the sampling error rate of flat epithelial atypia (FEA) and evaluated current guidelines recommending excisional biopsy.

METHODS: A retrospective review of consecutive excisional biopsies after image-guided core-needle biopsy identified patients with isolated FEA diagnosed between 2014 and 2018. Clinical and pathologic parameters were evaluated.

RESULTS: Twenty-five women with 27 biopsies were included. Based on pathologic review of original core specimens, 44.4% (N = 12) were accurately diagnosed as FEA. Upon excision, lesions were upgraded to ductal carcinoma in situ (N = 2) or invasive ductal carcinoma (N = 1) in 11.1% of cases. Older age, black race, hormone replacement, and calcifications in the image-guided biopsy specimen were associated with the presence of high-risk or malignant lesions in the excisional biopsy (all p ≤ 0.05).

CONCLUSIONS: In this study, FEA was frequently overcalled. However, lesions suspicious for FEA warrant excision due to their association with malignancy or high-risk lesions, which may necessitate further surgical management and/or risk-reducing strategies.}, } @article {pmid31391072, year = {2019}, author = {Tan, X and Li, Z and Ren, S and Rezaei, K and Pan, Q and Goldstein, AT and Macri, CJ and Cao, D and Brem, RF and Fu, SW}, title = {Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {89}, pmid = {31391072}, issn = {1465-542X}, mesh = {3' Untranslated Regions ; Breast Neoplasms/*genetics/*pathology/therapy ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; DNA Damage ; Disease Progression ; Drug Resistance, Neoplasm/*genetics ; Epithelial-Mesenchymal Transition/genetics ; Female ; Forkhead Box Protein M1/genetics ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; MicroRNAs/*genetics ; Models, Biological ; RNA Interference ; Radiation Tolerance/*genetics ; }, abstract = {BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.

METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.

RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.

CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.}, } @article {pmid31390230, year = {2019}, author = {Ortega, A and Olea-Herrero, N and Arenas, MI and Vélez-Vélez, E and Moreno-Gómez-Toledano, R and Muñoz-Moreno, C and Lázaro, A and Esbrit, P and Tejedor, A and Bosch, RJ}, title = {Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.}, journal = {American journal of physiology. Renal physiology}, volume = {317}, number = {4}, pages = {F874-F880}, doi = {10.1152/ajprenal.00091.2019}, pmid = {31390230}, issn = {1522-1466}, mesh = {Acute Kidney Injury/*chemically induced/pathology/*urine ; Animals ; Antineoplastic Agents/*toxicity ; Biomarkers/urine ; Cisplatin/*toxicity ; Creatinine/urine ; Kidney/pathology ; Kidney Function Tests ; Male ; Parathyroid Hormone-Related Protein/*urine ; Rats ; Rats, Wistar ; }, abstract = {Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.}, } @article {pmid31388122, year = {2020}, author = {Goodes, LM and King, GK and Rea, A and Murray, K and Boan, P and Watts, A and Bardsley, J and Hartshorn, C and Thavaseelan, J and Rawlins, M and Brock, JA and Dunlop, SA}, title = {Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.}, journal = {Spinal cord}, volume = {58}, number = {1}, pages = {25-34}, pmid = {31388122}, issn = {1476-5624}, mesh = {Adult ; Catheters, Indwelling/statistics & numerical data ; Humans ; Incidence ; Inpatients/statistics & numerical data ; Length of Stay/*statistics & numerical data ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications/*epidemiology ; Time Factors ; Urinary Catheterization/adverse effects/*statistics & numerical data ; Urinary Tract Infections/*epidemiology/etiology ; Western Australia/epidemiology ; }, abstract = {STUDY DESIGN: Retrospective audit.

OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).

SETTING: Western Australian Hospitals managing SCI patients.

METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.

RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively).

CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.

SPONSORSHIP: None.}, } @article {pmid31384485, year = {2019}, author = {Forte, S and Ritz, A and Kubik-Huch, R and Leo, C}, title = {Invasive ductal carcinoma detected within a fibroadenolipoma through digital breast tomosynthesis.}, journal = {Acta radiologica open}, volume = {8}, number = {7}, pages = {2058460119865905}, pmid = {31384485}, issn = {2058-4601}, abstract = {A 52-year-old patient referred to our hospital for a screening mammogram showed a suspicious new architectural distortion. Previously, a fibroadenolipoma within the right breast was diagnosed clinically and radiologically. Further work-up with tomosynthesis, magnetic resonance imaging, and magnetic resonance-guided biopsy showed an invasive ductal carcinoma within the fibroadenolipoma, which are usually benign breast lesions not associated with malignancy. This case report offers a review of the literature and a discussion of signs, which should alert the radiologist.}, } @article {pmid31376306, year = {2019}, author = {Borelli, JL and Shai, D and Fogel Yaakobi, S and Levit-Binnun, N and Golland, Y}, title = {Interpersonal physiological regulation during couple support interactions: Examining the role of respiratory sinus arrhythmia and emotional support.}, journal = {Psychophysiology}, volume = {56}, number = {11}, pages = {e13443}, doi = {10.1111/psyp.13443}, pmid = {31376306}, issn = {1540-5958}, mesh = {Adult ; Autonomic Nervous System/*physiology ; Emotional Regulation/*physiology ; Female ; Humans ; *Interpersonal Relations ; Male ; *Object Attachment ; Respiratory Sinus Arrhythmia/*physiology ; *Social Support ; Spouses/*psychology ; Young Adult ; }, abstract = {In times of need, people seek comfort and support from close others. Support provision is an integral component of attachment relationships, one that is linked with physical and psychological well-being. Successful support provision is believed to be grounded in transactions of sensitive, caring behavior between caregivers and support seekers and to serve a profound regulatory function. However, physiological processes underlying support transactions have not been previously studied. We assessed autonomic vagal regulation and coded spontaneous emotional support behaviors in N = 100 heterosexual couples involved in a support interaction. We focused on cardiac vagal activation, operationalized as the increase in respiratory sinus arrhythmia (RSA) from baseline to interaction, as an indicator of regulatory efforts. Analyses revealed a negative association between caregivers' and support seekers' regulatory efforts, which was mediated by emotional support behaviors. We found that caregivers with greater increases in RSA from baseline to interaction provided more emotional support to their partners. Such emotional support was associated with smaller increases in support seekers' RSA and with support seekers' perceptions of their partners as being more sensitive to their needs. Finally, these links were only significant among dyads in which caregivers reported lower levels of attachment anxiety. We interpret these results in the framework of interpersonal regulatory processes, suggesting that provision of support may impose regulatory demands on the side of the caregivers, which in turn could result in attenuated regulatory efforts and positive partner perceptions for the support seekers.}, } @article {pmid31372434, year = {2019}, author = {Levy, J and Démonet, JF}, title = {MEG data representing a gamma oscillatory response during the hold/release paradigm.}, journal = {Data in brief}, volume = {23}, number = {}, pages = {103787}, pmid = {31372434}, issn = {2352-3409}, abstract = {The article presents magnetoencephalography (MEG) data from healthy participants while undergoing the Hold/Release paradigm. During the paradigm, participants visually perceived a sequence of two letter strings which either assembled into real words (Hold condition) or pseudowords (Release condition). If the first letter string was morphologically valid, they held their attention (and/or held the item in working-memory) to wait for the second string, whereas if it were invalid, they could release it, respectively. We present data on high-frequency neuronal oscillations of the Hold condition compared to the Release condition. Making this information publicly available could allow other researchers to perform analyses and contribute to understanding the cognitive processes such as language, mnemonic or attentional processes.}, } @article {pmid31372053, year = {2019}, author = {Liu, J and Zhao, J and Zhang, M and Chen, N and Sun, G and Yang, Y and Zhang, X and Chen, J and Shen, P and Shi, M and Zeng, H}, title = {The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: a single-center retrospective study.}, journal = {Cancer management and research}, volume = {11}, number = {}, pages = {6521-6529}, pmid = {31372053}, issn = {1179-1322}, abstract = {INTRODUCTION: Since the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and it has shown excellent prognostic value. However, its predictive power in high-risk PCa remains unclear.

METHODS: A total of 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included in this study. Biochemical recurrence-free survival (BRFS) was set as the endpoint.

RESULTS: Biochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (P=0.593). Also, the prognosis between those with GG 2 and GG 3 could be clearly distinguished (P=0.001). However, the discrimination capacity between patients with GG 3 and GG 4 was limited (P=0.681). When tertiary Gleason pattern (TGP5) and intraductal carcinoma of the prostate (IDC-P) were excluded, the HR value of the GG 4 group vs the GG 3 group increased from 1.15 (95% CI: 0.59-2.22) to 1.49 (95% CI: 0.72-3.10) and 1.36 (95% CI:0.65-2.83), respectively.

CONCLUSIONS: This study is the first to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively classify patients into five groups with high predictive accuracy. Notably, the existence of TGP5 and IDC-P needs to be routinely reported in clinical practice, which could help to support the predictive value of the new grading system.}, } @article {pmid31365497, year = {2019}, author = {Can, C and Komek, H}, title = {Metabolic and volume-based parameters of (18F)FDG PET/CT for primary mass and axillary lymph node metastasis in patients with invasive ductal carcinoma: a retrospective analysis in relation to molecular subtype, axillary lymph node metastasis and immunohistochemistry and inflammatory markers.}, journal = {Nuclear medicine communications}, volume = {40}, number = {10}, pages = {1051-1059}, doi = {10.1097/MNM.0000000000001074}, pmid = {31365497}, issn = {1473-5628}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnostic imaging/*metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*metabolism/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Immunohistochemistry ; Inflammation/metabolism ; Lymphatic Metastasis ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Tumor Burden ; }, abstract = {OBJECTIVE: To evaluate metabolic and volume-based parameters of 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((F)FDG PET/CT) for primary mass and axillary lymph node (ALN) metastasis in relation to molecular subtype, and immunohistochemistry and inflammatory markers in patients with invasive ductal carcinoma.

METHODS: A total of 129 patients (mean±SD age: 49.2±13.0 years) with invasive ductal breast cancer who had (F)FDG PET/CT imaging prior to chemotherapy or surgery were included in this single-center retrospective study. Data on patient age, molecular subtype, ALN metastasis status, inflammatory markers, immunohistochemistry markers and (F)FDG PET/CT imaging parameters for primary mass and ALN were recorded.

RESULTS: ALN metastasis was evident in 52.7% of patients and associated with significantly higher median diameter (P=0.027), MTV (P<0.001) and TLG (P<0.001). NLR was positively correlated with all primary mass (p ranged from 0.041 to 0.001) and ALN (P ranged from 0.026 to <0.001) PET parameters. PET parameters did not change with respect to molecular subtype or immunohistochemistry markers. Primary mass and ALN metastasis PET parameters showed significant positive correlations for TLG (r=0.274, P=0.001) and SUVmax (r=0.358, P<0.001).

CONCLUSION: In conclusion, our findings in a retrospective cohort of invasive ductal breast cancer patients revealed primary mass PET parameters to significantly differ with respect to ALN metastasis status and NLR levels, but not according to molecular subtype or immunohistochemistry markers. Accordingly, our findings highlight the value of acquisition of preoperative PET/CT imaging and role of both metabolic and volume-based parameters in predicting aggressiveness of the tumor as correlated with presence of ALN metastasis and high NLR.}, } @article {pmid31365279, year = {2019}, author = {Metaxa, L and Healy, NA and O'Keeffe, SA}, title = {Breast microcalcifications: the UK RCR 5-point breast imaging system or BI-RADS; which is the better predictor of malignancy?.}, journal = {The British journal of radiology}, volume = {92}, number = {1103}, pages = {20190177}, pmid = {31365279}, issn = {1748-880X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Calcinosis/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Early Detection of Cancer ; Female ; Humans ; Mammography/methods ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Retrospective Studies ; }, abstract = {OBJECTIVE: In the UK RCR 5-point breast imaging system (UKS), radiologists grade mammograms from 1 to 5 according to suspicion for malignancy, however unlike BI-RADS, no lexicon of descriptors is published. The aim of this study was to determine whether strict categorisation of microcalcifications (MCC) according to BI-RADS was a better predictor of malignancy than the UKS and whether these descriptors could be used within the UKS.

METHODS: A retrospective review of 241 cases, with MCC on mammography, who underwent biopsy was performed. Morphology, distribution, extent, UKS score, BI-RADS category and pathology were recorded. The positive predictive value (PPV) of each classification system for malignancy was calculated.

RESULTS: 28.6% were diagnosed with DCIS/IDC. The PPV for malignancy using the UKS was 18.9%, 69.4%, 100% for M3-5 respectively (p < 0.001) and using ΒI-RADS morphology was amorphous: 7.1%, coarse heterogeneous: 33.3%, fine pleomorphic: 48.1% and fine linear/fine linear branching: 85.2% (p < 0.001). The PPV based on distribution was grouped: 14.2%, regional: 32.3%, diffuse: 33.3% and linear/segmental: 77.8% (p < 0.001). Combining all cases of benign-appearing, amorphous and grouped coarse heterogenous and grouped fine pleomorphic MCC gave a PPV of 12.8%. Combining regional, linear or segmental coarse heterogenous and fine pleomorphic and all fine linear/branching MCC resulted in a PPV of 83.3% for malignancy.

CONCLUSION: Combining morphology and distribution of MCC is accurate in malignancy prediction. Use of BI-RADS descriptors could help standardise reporting within the UKS and an algorithm using these within the UKS is proposed. Better prediction would enable more appropriate counselling and help to identify discrepancies.

ADVANCES IN KNOWLEDGE: No guidance exists on scoring of suspicious MCC in the UK breast imaging system. Use of BI-RADS morphologic/distribution descriptors can aid malignancy prediction. Findings other than morphology of MCC are important in malignancy prediction. An algorithm for use by the UK radiologist when evaluating MCC is provided.}, } @article {pmid31359912, year = {2019}, author = {Sinha, A and Gill, SS}, title = {Cytological Correlates of Axillary Nodal Involvement in Invasive Ductal Carcinoma of Breast.}, journal = {Journal of cytology}, volume = {36}, number = {3}, pages = {142-145}, pmid = {31359912}, issn = {0970-9371}, abstract = {CONTEXT: Fine needle aspiration cytology (FNAC) plays an important role in the diagnosis of breast carcinoma. However, its role as a prognostic tool needs to be explored. This can be achieved by studying its correlation with an established prognostic marker such as axillary nodal metastasis.

AIMS: This study was undertaken to correlate the cytological features of invasive ductal carcinoma (IDC) of breast with axillary lymph node status.

SETTINGS AND DESIGN: Tertiary care hospital, retrospective analytical study.

MATERIALS AND METHODS: The study group included 150 cases of IDC of breast diagnosed on FNAC, who had subsequently undergone modified radical mastectomy. Cytologic grades were assigned as per Robinson's grading system. Histopathological sections of axillary lymph nodes were assessed for metastasis.

STATISTICAL ANALYSIS USED: The cytologic grade and each feature of the cytologic grade were correlated with the lymph node metastasis using χ[2] test. Values of P < 0.05 were considered significant.

RESULT: A statistically significant correlation was noted between cytologic grade of tumor and axillary lymph node metastasis (P < 0.05). In addition, a positive correlation was found between two of the individual features of cytologic grade, namely, nuclear size and cell uniformity with axillary lymph node metastasis (P < 0.05).

CONCLUSION: Robinson's cytologic grade of breast carcinoma correlates well with the presence of axillary lymph node metastasis and hence can be used as a prognostic tool. As there is an increasing trend toward conservative approach to management of breast carcinoma, patients receive preoperative neoadjuvant therapy which may alter the nodal status on the resected specimen. Hence, a high cytological grade of primary tumor, as assessed on FNAC before initiation of therapy, should alert the treating team of the possibility of axillary lymph nodal metastasis.}, } @article {pmid31358786, year = {2019}, author = {Chang, CC and Chen, CJ and Hsu, WL and Chang, SM and Huang, YF and Tyan, YC}, title = {Prognostic Significance of Metabolic Parameters and Textural Features on [18]F-FDG PET/CT in Invasive Ductal Carcinoma of Breast.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {10946}, pmid = {31358786}, issn = {2045-2322}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Fluorodeoxyglucose F18 ; Glycolysis ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Positron Emission Tomography Computed Tomography/*standards ; Predictive Value of Tests ; Radiopharmaceuticals ; Survival Analysis ; }, abstract = {To investigate the prognostic significance of metabolic parameters and texture analysis on [18]F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast invasive ductal carcinoma (IDC), from August 2005 to May 2015, IDC patients who had undergone pre-treatment FDG PET/CT were enrolled. The metabolic parameters, including maximal standardized uptake value of breast tumor (SUVbt) and ipsilateral axillary lymph node (SUVln), metabolic tumor volume (MTVbt) and total lesion glycolysis (TLGbt) of breast tumor, whole-body MTV (MTVwb) and whole-body TLG (TLGwb) were recorded. Nine textural features of tumor (four co-occurrence matrices and five SUV-based statistics) were measured. The prognostic significance of above parameters and clinical factors was assessed by univariate and multivariate analyses. Thirty-five patients were enrolled. Patients with low and high MTVwb had 5-year progression-free survival (PFS) of 81.0 and 14.3% (p < 0.0001). The 5-year overall survival for low and high MTVwb was 88.5% and 43.6% (p = 0.0005). Multivariate analyses showed MTVwb was an independent prognostic factor for PFS (HR: 8.29, 95% CI: 2.17-31.64, p = 0.0020). The SUV, TLG and textural features were not independently predictive. Elevated MTVwb was an independent predictor for shorter PFS in patients with breast IDC.}, } @article {pmid31357843, year = {2019}, author = {Li, TT and Kang, CS and Li, HZ and Xue, JP and Yang, QM and Lyu, J}, title = {[Value of shear wave elastrography image classification in the diagnosis of breast masses].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {41}, number = {7}, pages = {540-545}, doi = {10.3760/cma.j.issn.0253-3766.2019.07.011}, pmid = {31357843}, issn = {0253-3766}, mesh = {Breast/*diagnostic imaging ; Breast Diseases/*classification/diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating ; Diagnosis, Differential ; Elasticity Imaging Techniques/*methods/standards ; Female ; Fibroadenoma ; Humans ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {Objective: To analyze the image features of shear wave elastrography (SWE) in breast masses, and to evaluate their values in the differentiation of benign and malignant breast lesions. Methods: A total of 361 patients with 403 breast lesions who simultaneously underwent conventional ultrasound and SWE examination from February 2015 to January 2018 were selected. Diagnosis in all patients was confirmed by aspiration biopsy or operative pathology. The SWE images were collected and the elastic images were divided into 5 types. The SWE image features of different breast pathological types were summarized, and their values in benign and malignant breast lesion diagnoses were evaluated. Results: The main features of benign breast lesion were type Ⅰ and Ⅱ, the main features of the malignant lesion were type Ⅳ and Ⅴ, and the proportion of which were 43.6% (71/163), 37.4% (61/163), 22.1% (53/240) and 57.9% (139/240), respectively. Type Ⅲ accounted for a certain proportion in both benign and malignant lesions. The SWE image features of benign and malignant lesions were compared and a significant difference was observed (P<0.001). The type Ⅴ features were mainly observed in invasive ductal carcinoma, invasive lobular carcinoma and other types of invasive carcinoma, while the type Ⅳ features were mostly presented in ductal carcinoma in situ and mucinous carcinoma. Fibroadenoma, fibroadenosis accompanied with fibroadenoma, and fibroadenosis were featured with type Ⅰ. Both intraductal papilloma and benign phyllodes tumor were mostly type Ⅱ, while type Ⅲ and Ⅴ were more common in chronic granulomatous mastitis. When type Ⅰ and typeⅡof breast lesions were classified as benign features while type Ⅳ and Ⅴ were malignant features, the sensitivity and specificity of breast malignant lesion diagnosis were 91.2% and 84.7% by application of SWE combined with breast imaging reporting and data system (BI-RADS). The sensitivity of combined diagnosis was slightly lower than that of conventional ultrasound (P>0.05), but the specificity was significantly higher than conventional ultrasound (P<0.01). Conclusion: The SWE is a simple and effective method. Combination of SWE with conventional ultrasound may improve the diagnostic differentiation of benign and malignant breast lesions.}, } @article {pmid31357083, year = {2019}, author = {Arabpour, M and Rasolmali, R and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.}, journal = {Molecular immunology}, volume = {114}, number = {}, pages = {172-178}, doi = {10.1016/j.molimm.2019.07.019}, pmid = {31357083}, issn = {1872-9142}, mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD40 Ligand/immunology ; Carcinoma, Ductal/immunology ; Female ; Granzymes/*immunology ; Humans ; Interleukins/immunology ; Lymph Nodes/*immunology ; Lymphocyte Activation/*immunology ; Middle Aged ; Perforin/immunology ; }, abstract = {B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB[+] B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB[+] B cells were perforin-negative. Both naïve (CD24[low]CD27[-]) and active/memory (CD24[hi]CD27[+]) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB[+] B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB[+] B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB[+] B cells in breast tumor immunity.}, } @article {pmid31354196, year = {2019}, author = {Ogunleye, AJ and Olanrewaju, AJ and Arowosegbe, M and Omotuyi, OI}, title = {Molecular docking based screening analysis of GSK3B.}, journal = {Bioinformation}, volume = {15}, number = {3}, pages = {201-208}, pmid = {31354196}, issn = {0973-2063}, abstract = {GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.}, } @article {pmid31352554, year = {2019}, author = {Zacharioudakis, K and Kontoulis, T and Vella, JX and Zhao, J and Ramakrishnan, R and Cunningham, DA and Mufti, RA and Leff, DR and Thiruchelvam, P and Hogben, K and Hadjiminas, DJ}, title = {Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.}, journal = {Breast cancer research and treatment}, volume = {178}, number = {1}, pages = {115-120}, pmid = {31352554}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Preoperative Period ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.

METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.

RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.

CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients with PND.}, } @article {pmid31351155, year = {2019}, author = {Ding, Q and Chen, H and Lim, B and Damodaran, S and Chen, W and Tripathy, D and Piha-Paul, S and Luthra, R and Meric-Bernstam, F and Sahin, AA}, title = {HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {32-38}, doi = {10.1016/j.humpath.2019.07.006}, pmid = {31351155}, issn = {1532-8392}, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Receptor, ErbB-2/*genetics/metabolism ; Retrospective Studies ; }, abstract = {HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n = 14) and extracellular (n = 4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor positive; the 4 cases with extracellular domain mutations were exclusively estrogen receptor negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of nonclassic ILC.}, } @article {pmid31350286, year = {2019}, author = {Lourenco, C and Kalkat, M and Houlahan, KE and De Melo, J and Longo, J and Done, SJ and Boutros, PC and Penn, LZ}, title = {Modelling the MYC-driven normal-to-tumour switch in breast cancer.}, journal = {Disease models & mechanisms}, volume = {12}, number = {7}, pages = {}, pmid = {31350286}, issn = {1754-8411}, support = {//CIHR/Canada ; }, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; }, abstract = {The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CA[H1047R]) led to the development of organised acinar structures in mice. Expressing both PIK3CA[H1047R] and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay invivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.}, } @article {pmid31342393, year = {2019}, author = {Champion, CD and Ren, Y and Thomas, SM and Fayanju, OM and Rosenberger, LH and Greenup, RA and Menendez, CS and Hwang, ES and Plichta, JK}, title = {DCIS with Microinvasion: Is It In Situ or Invasive Disease?.}, journal = {Annals of surgical oncology}, volume = {26}, number = {10}, pages = {3124-3132}, pmid = {31342393}, issn = {1534-4681}, support = {K12 HD043446/HD/NICHD NIH HHS/United States ; KL2 TR002554/TR/NCATS NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; P30CA014236/GF/NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes.

METHODS: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively.

RESULTS: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93).

CONCLUSIONS: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.}, } @article {pmid31342363, year = {2019}, author = {Mamtani, A and Zabor, EC and Stempel, M and Morrow, M}, title = {Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.}, journal = {Annals of surgical oncology}, volume = {26}, number = {10}, pages = {3269-3274}, pmid = {31342363}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision/*methods ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prospective Studies ; }, abstract = {BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned.

METHODS: From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients.

RESULTS: Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2 mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42 months, there were no isolated axillary recurrences.

CONCLUSIONS: Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.}, } @article {pmid31341449, year = {2019}, author = {Oluogun, WA and Adedokun, KA and Oyenike, MA and Adeyeba, OA}, title = {Histological classification, grading, staging, and prognostic indexing of female breast cancer in an African population: A 10-year retrospective study.}, journal = {International journal of health sciences}, volume = {13}, number = {4}, pages = {3-9}, pmid = {31341449}, issn = {1658-3639}, abstract = {BACKGROUND: Breast cancer (BC) is a heterogeneous disease characterized with diverse genetic and ethnic/racial variations that may influence tumor characteristics and prognosis. We studied different histological types of BC and their prognostic indicators in part of Southwestern Nigeria.

MATERIALS AND METHODS: A 10-year retrospective study of archival tissue-paraffin blocks and records of surgical cases (documented as BCs) between January 2005 and December 2014 was done. Tumor classification was made after the World Health Organization guidelines. Modified Bloom-Richardson score and TNM staging system were used in grading and staging the tumors. Nottingham prognostic index was employed in scoring the prognosis.

RESULTS: The mean age was 49.7 years (20-89 years). The age group from 50 to 59 years was most affected. Out of 343 total cases, the most common histological type was invasive ductal carcinoma of no special type (88.9%). The majority (51.9%) had tumor sizes ranging 2-5 cm (pT2) and some (39.1%) with >5 cm (pT3) were all at palpable stages. The tumors were mostly Grades II and III types. Observation for lymph node metastasis confirmed that 261 (76.1%) were pN0 (negative), 77 (22.4%) were pN1, and 5 (1.5%) were pN2. Prediction of a chance of survival showed moderate prognosis in the majority (48.7%) of the cases.

CONCLUSION: Although early detection of BC in this region was considerably poor, there was a better outcome compared with some other black populations. Clinical presentation, histological type, and prognostic indices varied from existing reports in many ethnic/racial groups. Indexing of BC pattern on a regional standpoint may serve a new direction toward better management considering the associated geographic disparity.}, } @article {pmid31339241, year = {2019}, author = {Lurie, I and Nakash, O and Gerber, Y and Gross, R}, title = {[THE ASSOCIATION BETWEEN EXPOSURE TO TRAUMA AND MENTAL ILLNESS AMONG WORK MIGRANTS AND ASYLUM SEEKERS IN ISRAEL: A SURVEY AT THE OPEN CLINIC, PHYSICIANS FOR HUMAN RIGHTS, 2012-2013].}, journal = {Harefuah}, volume = {158}, number = {7}, pages = {432-436}, pmid = {31339241}, issn = {0017-7768}, mesh = {Adult ; Cross-Sectional Studies ; Human Rights ; Humans ; Israel ; *Refugees ; *Stress Disorders, Post-Traumatic ; Surveys and Questionnaires ; *Transients and Migrants ; }, abstract = {INTRODUCTION: In 2012, 183,896 work migrants and 47,704 asylum-seekers and work-migrants arrived in Israel. These populations are at high-risk for depression, anxiety and posttraumatic stress disorder (PTSD). The Open Clinic of Physicians for Human Rights (PHR) delivers free medical and mental health services to these individuals.

AIMS: To evaluate exposure to traumatic events, and compare the prevalence and risk for PTSD, depression and anxiety symptoms between work-migrants and asylum-seekers.

METHODS: An analytical cross-sectional study of adults visiting the Open Clinic was conducted. Participants completed self-report questionnaires including information on demographics and exposure to traumas, depression, anxiety and PTSD. Statistical models were constructed to predict outcome variables of PTSD, depression and anxiety as dichotomist variables using a logistic regression, and association odds ratio (OR) and confidence interval (CI) on 95% level.

RESULTS: There were 241 participants; 165 asylum-seekers, 76 work-migrants. Work-migrants were exposed to more traumatic events. A total of 17-31% met PTSD criteria. Significantly more asylum-seekers met PTSD criteria. A total of 43%-50% met criteria for depression and/or anxiety, with no between-group differences. Significant association was found between immigration status and PTSD risk. Exposure to traumatic events was significantly associated with the prediction of PTSD, depression and anxiety.

DISCUSSION: Exposure to traumatic events was high among the Open Clinic service users, specifically work-migrants. Prevalence and risk for post-traumatic symptoms were significantly higher among asylum-seekers. It is important to conduct further research, in order to characterize risk and resilience factors in this excluded population, and to plan language and culture-competent mental health services.}, } @article {pmid31338037, year = {2019}, author = {Rodriguez, J and Schulz, S and Giraldo, BF and Voss, A}, title = {Risk Stratification in Idiopathic Dilated Cardiomyopathy Patients Using Cardiovascular Coupling Analysis.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {841}, pmid = {31338037}, issn = {1664-042X}, abstract = {Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.}, } @article {pmid31331823, year = {2019}, author = {Machado, J and Silveira, WA and Gonçalves, DA and Schavinski, AZ and Khan, MM and Zanon, NM and Diaz, MB and Rudolf, R and Kettelhut, IC and Navegantes, LC}, title = {α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles.}, journal = {Molecular metabolism}, volume = {28}, number = {}, pages = {91-106}, pmid = {31331823}, issn = {2212-8778}, mesh = {Animals ; Autophagy/*drug effects ; Calcitonin Gene-Related Peptide/*pharmacology ; Calpain/*antagonists & inhibitors/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*drug effects/metabolism ; Neuromuscular Junction/*drug effects/metabolism ; Vasodilator Agents/*pharmacology ; }, abstract = {OBJECTIVE: Although it is well established that a-calcitonin gene-related peptide (CGRP) stabilizes muscle-type cholinergic receptors nicotinic subunits (AChR), the underlying mechanism by which this neuropeptide regulates muscle protein metabolism and neuromuscular junction (NMJ) morphology is unclear.

METHODS: To elucidate the mechanisms how CGRP controls NMJ stability in denervated mice skeletal muscles, we carried out physiological, pharmacological, and molecular analyses of atrophic muscles induced by sciatic nerve transection.

RESULTS: Here, we report that CGRP treatment in vivo abrogated the deleterious effects on NMJ upon denervation (DEN), an effect that was associated with suppression of skeletal muscle proteolysis, but not stimulation of protein synthesis. CGRP also blocked the DEN-induced increase in endocytic AChR vesicles and the elevation of autophagosomes per NMJ area. The treatment of denervated animals with rapamycin blocked the stimulatory effects of CGRP on mTORC1 and its inhibitory actions on autophagic flux and NMJ degeneration. Furthermore, CGRP inhibited the DEN-induced hyperactivation of Ca[2+]-dependent proteolysis, a degradative system that has been shown to destabilize NMJ. Consistently, calpain was found to be activated by cholinergic stimulation in myotubes leading to the dispersal of AChR clusters, an effect that was abolished by CGRP.

CONCLUSION: Taken together, these data suggest that the inhibitory effect of CGRP on autophagy and calpain may represent an important mechanism for the preservation of synapse morphology when degradative machinery is exacerbated upon denervation conditions.}, } @article {pmid31331321, year = {2019}, author = {Nkinda, L and Patel, K and Njuguna, B and Ngangali, JP and Memiah, P and Bwire, GM and Majigo, MV and Mizinduko, M and Pastakia, SD and Lyamuya, E}, title = {C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.}, journal = {BMC endocrine disorders}, volume = {19}, number = {1}, pages = {77}, pmid = {31331321}, issn = {1472-6823}, support = {-//Intra-ACP academic mobility scholarship/ ; }, mesh = {Biomarkers/*blood ; Blood Glucose/*analysis ; C-Reactive Protein/*analysis ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Glucose Intolerance/*blood/epidemiology/virology ; HIV/*isolation & purification ; HIV Infections/*complications/virology ; Humans ; Incidence ; Interleukin-6/*blood ; Male ; Middle Aged ; Prognosis ; Tanzania/epidemiology ; }, abstract = {BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania.

METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant.

RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m[2]), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia.

CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.}, } @article {pmid31324579, year = {2020}, author = {Mojahed, D and Ha, RS and Chang, P and Gan, Y and Yao, X and Angelini, B and Hibshoosh, H and Taback, B and Hendon, CP}, title = {Fully Automated Postlumpectomy Breast Margin Assessment Utilizing Convolutional Neural Network Based Optical Coherence Tomography Image Classification Method.}, journal = {Academic radiology}, volume = {27}, number = {5}, pages = {e81-e86}, pmid = {31324579}, issn = {1878-4046}, support = {DP2 HL127776/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging/*pathology/*surgery ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Margins of Excision ; Mastectomy, Segmental/*methods ; *Neural Networks, Computer ; Postoperative Period ; Tomography, Optical Coherence/*methods ; }, abstract = {BACKGROUND: The purpose of this study was to develop a deep learning classification approach to distinguish cancerous from noncancerous regions within optical coherence tomography (OCT) images of breast tissue for potential use in an intraoperative setting for margin assessment.

METHODS: A custom ultrahigh-resolution OCT (UHR-OCT) system with an axial resolution of 2.7 μm and a lateral resolution of 5.5 μm was used in this study. The algorithm used an A-scan-based classification scheme and the convolutional neural network (CNN) was implemented using an 11-layer architecture consisting of serial 3 × 3 convolution kernels. Four tissue types were classified, including adipose, stroma, ductal carcinoma in situ, and invasive ductal carcinoma.

RESULTS: The binary classification of cancer versus noncancer with the proposed CNN achieved 94% accuracy, 96% sensitivity, and 92% specificity. The mean five-fold validation F1 score was highest for invasive ductal carcinoma (mean standard deviation, 0.89 ± 0.09) and adipose (0.79 ± 0.17), followed by stroma (0.74 ± 0.18), and ductal carcinoma in situ (0.65 ± 0.15).

CONCLUSION: It is feasible to use CNN based algorithm to accurately distinguish cancerous regions in OCT images. This fully automated method can overcome limitations of manual interpretation including interobserver variability and speed of interpretation and may enable real-time intraoperative margin assessment.}, } @article {pmid31323601, year = {2019}, author = {Yamba, K and Kalinowski, MB and Sanogo, O}, title = {On the usability of event zero time determinations using radioxenon isotopic activity ratios given the real atmospheric background observations.}, journal = {Journal of environmental radioactivity}, volume = {208-209}, number = {}, pages = {106014}, doi = {10.1016/j.jenvrad.2019.106014}, pmid = {31323601}, issn = {1879-1700}, mesh = {Air Pollutants, Radioactive/*analysis ; Atmosphere/chemistry ; Nevada ; Nuclear Weapons ; *Radiation Monitoring ; Reference Values ; Xenon Radioisotopes/*analysis ; }, abstract = {This work focuses on the usability of event zero time determination using xenon isotopic activity ratios. Two data sets from Nevada underground nuclear test and Fukushima accident debris were used to calculate the age of radioxenon release by considering three kinds of radioactivity release radionuclide sources: nuclear explosion scenarios, nuclear power reactor release and medical isotopes production facilities release. Typical nuclear power reactor releases were characterized and reference values are proposed for six isotopic activity ratios, which data can be considered as reference point of nuclear reactor effluents at the time of their release obtained from real observations. The same reference values of isotopic activity ratio are given for medical isotopes production facilities releases. The purpose of this study is to evaluate the use of zero-time calculation for source characterization under the assumption that a hypothesis about the event time is made. The event time information may come from a seismo-acoustic event of interest or an inverse atmospheric transport simulation or other context information. For both data sets used in this study, the age precisions are calculated and the time precision difference is evaluated and used as a parameter for the characterization of each radionuclide event. Almost all radioxenon isotopic activity ratios are found to correctly identifying the source type of the radionuclide events studied in this work. The results from this radionuclide events characterization study may be helpful for event screening activities of the Comprehensive Nuclear Test Ban Treaty Organization (CTBTO).}, } @article {pmid31321854, year = {2019}, author = {Lewis, GD and Xing, Y and Haque, W and Patel, T and Schwartz, MR and Chen, AC and Farach, A and Hatch, SS and Butler, EB and Chang, JC and Teh, BS}, title = {The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast.}, journal = {The breast journal}, volume = {25}, number = {6}, pages = {1171-1176}, doi = {10.1111/tbj.13432}, pmid = {31321854}, issn = {1524-4741}, mesh = {Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/pathology ; Carcinoma, Papillary/*mortality/*pathology ; Female ; Humans ; Middle Aged ; Proportional Hazards Models ; Receptor, ErbB-2 ; Registries ; Retrospective Studies ; Survival Analysis ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.}, } @article {pmid31321627, year = {2019}, author = {Borlinhas, F and Conceição, RC and Ferreira, HA}, title = {Optimal b-values for diffusion kurtosis imaging in invasive ductal carcinoma versus ductal carcinoma in situ breast lesions.}, journal = {Australasian physical & engineering sciences in medicine}, volume = {42}, number = {3}, pages = {871-885}, doi = {10.1007/s13246-019-00773-2}, pmid = {31321627}, issn = {1879-5447}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Diagnosis, Differential ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; *Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Invasiveness ; Signal-To-Noise Ratio ; }, abstract = {Diffusion kurtosis imaging (DKI) is a diffusion-weighted MRI technique that probes the non-Gaussian diffusion of water molecules within biological tissues. The purpose of this study was to investigate the DKI model optimal b-values combinations in invasive ductal carcinoma (IDC) versus ductal carcinoma in situ (DCIS) breast lesions. The study included 114 malignant breast lesions (64 IDC and 50 DCIS). Patients underwent a breast MRI examination which included a diffusion-weighted sequence (b = 0-3000 s/mm[2]). For each lesion, the b-values were combined among each other (109 combinations) and each mean kurtosis (MK) parameter was obtained. Differences between the lesion groups and b-values combinations were assessed. Also, the diagnostic performance of the combinations was determined through receiver operating characteristic (ROC) curve analysis, and compared. Root mean square error (RMSE) was also obtained. All the b-values combinations showed significant differences between the lesion groups (p < 0.05). The combination 0, 50, 200, 750, 1000, 2000 s/mm[2] showed the best performance (AUC = 0.930, sensitivity = 95.3%, specificity = 82.0%, accuracy = 89.5%), with a RMSE of 17.65. The b-values combinations with the worst performance were composed of only high or ultra-high b-values, or with b = 1000 s/mm[2] as the maximum b-value. Better results were obtained when zero b-value was included in the DKI model fitting with at least one b-value below 1000 s/mm[2] and one b-value above 1000 s/mm[2] (conserving b = 1000 s/mm[2]). Six was the optimal number of b-values, nonetheless other combinations with less b-values may be considered, but with a consequent diagnostic performance loss.}, } @article {pmid31321184, year = {2019}, author = {Mukhtar, RA and Holland, M and Sieber, DA and Wen, KW and Rugo, HS and Kadin, ME and Bean, GR}, title = {Synchronous Breast Implant-associated Anaplastic Large Cell Lymphoma and Invasive Carcinoma: Genomic Profiling and Management Implications.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {7}, number = {4}, pages = {e2188}, pmid = {31321184}, issn = {2169-7574}, abstract = {A 59-year-old woman with a history of cosmetic implants developed ipsilateral synchronous breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and invasive ductal carcinoma in the left breast. Each tumor was subjected to next-generation sequencing, and separate analyses revealed mutually exclusive aberrations: an activating STAT3 mutation in the lymphoma and a PIK3CA in-frame deletion in the carcinoma. The patient was treated with removal of implants, capsulectomy, partial mastectomy, sentinel node biopsy, radiotherapy, and endocrine therapy with no evidence of recurrence for 1 year. This case illustrates the importance of obtaining thorough evaluation for concomitant malignancies in the breast at the time of diagnosis of BIA-ALCL. Herein, we review the current recommendations for evaluation and management of BIA-ALCL.}, } @article {pmid31320870, year = {2019}, author = {Kitahara, M and Hozumi, Y and Nakamura, A and Tachi, K and Saitoh, H and Iijima, T}, title = {HER2-Positive Conversion in a Metastatic Liver Focus in Late Recurrent Breast Cancer.}, journal = {Case reports in oncology}, volume = {12}, number = {2}, pages = {473-479}, pmid = {31320870}, issn = {1662-6575}, abstract = {Late recurrence of estrogen receptor (ER) positive breast cancer is common. When tissues from a recurrent or metastatic focus are available, re-evaluation of ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status is recommended for treatment selection. This case report describes a 59-year-old woman who underwent surgery for left breast cancer, with a histopathological diagnosis of invasive ductal carcinoma (pathological stage T2N1aM0 Stage IIB, ER positive, PgR positive and HER2 negative). A health check-up 16 years after surgery revealed multiple hepatic mass lesions, and the patient was referred to our hospital for tests. Based on computed tomography, intrahepatic bile duct cancer or metastatic hepatic tumors were suspected, and a liver biopsy was performed. The histopathological diagnosis was a poorly differentiated adenocarcinoma (ER negative, PgR negative and HER2 positive), and the distinction from poorly differentiated intrahepatic bile duct cancer was difficult. Fluorodeoxyglucose (FDG)-positron emission tomography revealed FDG accumulation in the patient's bones and soft tissues, in addition to the hepatic tumors. The patterns and finding of metastasis were compatible with breast cancer recurrence, and the patient was diagnosed with postoperative recurrence of left breast cancer. Pertuzumab, trastuzumab, and docetaxel were started, and the therapeutic effect was assessed as a partial response. It was evident that in this case, the expression of hormone receptors and HER2 differed between the primary focus and the recurrence foci, and this contributed to the treatment strategy. Whenever possible, a biopsy should be performed for lesions that are suspected to be distal metastases.}, } @article {pmid31319513, year = {2019}, author = {Fang, A and Dong, J and Zhang, R}, title = {Simulation of Heavy Metals Migration in Soil-Wheat System of Mining Area.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31319513}, issn = {1660-4601}, mesh = {China ; Edible Grain/chemistry ; Environmental Monitoring ; Metals, Heavy/analysis/*metabolism ; Mining ; Regression Analysis ; Soil ; Soil Pollutants/analysis/*metabolism ; Triticum/*metabolism ; }, abstract = {Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg[-1]), Pb (20.08 mg·kg[-1]), and Zn (39.11 mg·kg[-1]) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg[-1]. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G (r) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.}, } @article {pmid31312789, year = {2019}, author = {Durhan, G and Azizova, A and Önder, Ö and Kösemehmetoğlu, K and Karakaya, J and Akpınar, MG and Demirkazık, F and Üner, A}, title = {Imaging Findings and Clinicopathological Correlation of Breast Cancer in Women under 40 Years Old.}, journal = {European journal of breast health}, volume = {15}, number = {3}, pages = {147-152}, pmid = {31312789}, issn = {2587-0831}, abstract = {OBJECTIVE: The aim of this study was to evaluate the clinical, imaging and histopathological features of breast cancer in patients aged under 40 years of age. The relationship between radiological characteristics and histopathological features was also investigated.

MATERIALS AND METHODS: The study included 131 patients aged under 40 years, diagnosed pathologically with breast cancer. A retrospective evaluation was made of the imaging and clinicopathological findings and the relationship between pathological and imaging findings was investigated.

RESULTS: Most of the cancers were detected from clinical symptoms, especially a palpable mass (76.3%). The most common histological type of tumor was invasive ductal carcinoma and 64.8% of the tumors were high grade tumors. The predominant features were irregular borders (92.4%), microlobulated-angulated contours (43.5%), hypo-homogeneous internal echogenicity (80.9%) on ultrasonography, and the presence of a mass (41.2%) and suspicious microcalcifications (40.2%) on mammography. Magnetic resonance imaging commonly showed mass enhancement (66.7%) with type 2 or 3 dynamic curve (92.6%). High-grade tumors were associated with posterior acoustic enhancement (p: 0.03) while low-grade tumors presented with spiculated margins more than high grade tumors (p: 0.04).

CONCLUSION: Breast cancer in women aged under 40 years usually presents with a self-detected palpable mass and can show different imaging findings according to the histological grade. Ultrasonography is the main modality for the diagnosis of breast cancer in young women, but mammography and magnetic resonance imaging can help in both diagnosis and evaluation of the extent of disease.}, } @article {pmid31312338, year = {2019}, author = {Traoré, B and Koulibaly, M and Diallo, A and Bah, M}, title = {Molecular profile of breast cancers in Guinean oncological settings.}, journal = {The Pan African medical journal}, volume = {33}, number = {}, pages = {22}, pmid = {31312338}, issn = {1937-8688}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*pathology ; Breast Neoplasms, Male/epidemiology/genetics/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Guinea/epidemiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/epidemiology/*pathology ; }, abstract = {Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.}, } @article {pmid31309844, year = {2019}, author = {Sorriso, A and Sorrentino, P and Rucco, R and Mandolesi, L and Ferraioli, G and Franceschini, S and Ambrosanio, M and Baselice, F}, title = {An automated magnetoencephalographic data cleaning algorithm.}, journal = {Computer methods in biomechanics and biomedical engineering}, volume = {22}, number = {14}, pages = {1116-1125}, doi = {10.1080/10255842.2019.1634695}, pmid = {31309844}, issn = {1476-8259}, mesh = {*Algorithms ; Automation ; Databases as Topic ; Humans ; *Magnetoencephalography ; Statistics as Topic ; }, abstract = {The problem of cleaning magnetoencephalographic data is addressed in this manuscript. At present, several denoising procedures have been proposed in the literature, nevertheless their adoption is limited due to the difficulty in implementing and properly tuning the algorithms. Therefore, as of today, the gold standard remains manual cleaning. We propose an approach developed with the aim of automating each step of the manual cleaning. Its peculiarities are the ease of implementation and using and the remarkable reproducibility of the results. Interestingly, the algorithm has been designed to imitate the reasoning behind the manual procedure, carried out by trained experts. Our statistical analysis shows that no significant differences can be found between the two approaches.}, } @article {pmid31308566, year = {2019}, author = {Malik, SS and Baig, M and Khan, MB and Masood, N}, title = {Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {69}, number = {7}, pages = {976-980}, pmid = {31308566}, issn = {0030-9982}, mesh = {Adult ; Age Factors ; Antineoplastic Agents/*therapeutic use ; Body Mass Index ; Breast Neoplasms/epidemiology/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/pathology/*therapy ; Cohort Studies ; Combined Modality Therapy ; Consanguinity ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Obesity/epidemiology ; Overweight/epidemiology ; Pakistan/epidemiology ; Prospective Studies ; Radiotherapy/*methods ; Risk Factors ; Survival Analysis ; Survival Rate ; }, abstract = {OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups.

METHODS: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24.

RESULTS: There were 347 subjects with a mean age of 44.3±12.2 years and body mass index of 27.9±4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options.

CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.}, } @article {pmid31307644, year = {2019}, author = {Bae, MS and Bernard-Davila, B and Sung, JS and Morris, EA}, title = {Preoperative breast MRI features associated with positive or close margins in breast-conserving surgery.}, journal = {European journal of radiology}, volume = {117}, number = {}, pages = {171-177}, pmid = {31307644}, issn = {1872-7727}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; *Magnetic Resonance Imaging/methods ; Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: To determine preoperative magnetic resonance imaging (MRI) features associated with positive or close margins in patients with breast cancer who underwent breast-conserving surgery (BCS).

MATERIALS AND METHODS: A retrospective review identified 249 patients with invasive ductal carcinoma (IDC) who underwent preoperative MRI and BCS as a primary procedure between 2008 and 2010. The MR images were reviewed for descriptions of findings with no new interpretations made. Margins were defined as positive (tumor touching the inked specimen margin), close (<2 mm tumor-free margin), or negative (≥2 mm tumor-free margin). Multivariate logistic regression analysis was performed to evaluate imaging and clinical factors predictive of positive or close margins.

RESULTS: Of the 249 patients, 83 (33.3%) had positive or close margins and 166 (66.7%) had negative margins on the initial BCS specimen. Multivariate analysis showed that multifocal disease (odds ratio, 4.8; 95% CI, 1.9-12.2; p =  0.001), nonmass enhancement lesion (odds ratio, 3.0; 95% CI, 1.5-6.2, p =  0.003), greater background parenchymal enhancement (odds ratio, 2.5; 95% CI, 1.1-5.6; p =  0.023), larger lesion size (odds ratio, 1.3; 95% CI, 1.0-1.7, p =  0.032), and presence of ductal carcinoma in situ on needle biopsy (odds ratio, 2.4; 95% CI, 1.3-4.6; p = 0.008) were independent predictors of positive or close margins.

CONCLUSIONS: Multifocal disease, nonmass enhancement lesion, or greater background parenchymal enhancement on preoperative breast MRI were significantly associated with positive or close margins. Identifying these MRI features before surgery can be helpful to reduce the reoperation rate in BCS.}, } @article {pmid31306700, year = {2019}, author = {Carvalho, MET and Oliveira, WF and Cunha, CRA and Coelho, LCBB and Silva, MV and Carvalho Junior, LB and Santos, BS and Cabral Filho, PE and Fontes, A and Correia, MTS}, title = {Evaluating the glycophenotype on breast cancer tissues with quantum dots-Cramoll lectin conjugates.}, journal = {International journal of biological macromolecules}, volume = {138}, number = {}, pages = {302-308}, doi = {10.1016/j.ijbiomac.2019.07.088}, pmid = {31306700}, issn = {1879-0003}, mesh = {Breast Neoplasms/metabolism/*pathology ; Fabaceae/*chemistry ; Glycosylation ; Humans ; Optical Phenomena ; *Phenotype ; Plant Lectins/*chemistry ; Polysaccharides/*metabolism ; Quantum Dots/*chemistry/*metabolism ; }, abstract = {During carcinogenesis, changes in the glycosylation can modulate many biological processes. Thus, the interest in exploring and understanding the roles of carbohydrates as cancer biomarkers has been increasing. Lectins have been applied as useful tools in glycobiology, especially when associated with fluorescent reporters. Therefore, to take advantage of the physicochemical properties of quantum dots (QDs), herein, we conjugated Cramoll, a lectin that recognizes glucose/mannose residues, with those nanoparticles. We applied the conjugates to investigate the glycocode of normal, fibroadenoma (FB), and invasive ductal carcinoma (IDC) human breast tissues. Additionally, we proposed a method to quantitatively evaluate the tissue labeling intensity by a fluorescence microplate assay (FMA). Conjugates showed intense fluorescence and specificity. The lectin activity and secondary structure were also preserved after the conjugation with QDs. Moreover, fluorescence images showed that ductal cells of normal and FB tissues were preferentially labeled by conjugates, whereas both cells and stroma were strongly labeled in IDC. FMA showed in a quantitative, practical, and sensitive way that the level of exposed glucose/mannose residues increased accordingly to the sample malignancy degree. In conclusion, QDs-Cramoll conjugates can be considered effective, specific, and versatile probes to evaluate glycan profiles in normal and transformed tissues, by fluorescence microscopy as well as FMA quantification. Furthermore, FMA showed to be a potential method that can be applied with other fluorescent conjugates.}, } @article {pmid31305879, year = {2019}, author = {Vaziri Fard, E and Ali, Y and Wang, XI and Saluja, K and H Covinsky, M and Wang, L and Zhang, S}, title = {Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma.}, journal = {American journal of clinical pathology}, volume = {152}, number = {5}, pages = {656-665}, doi = {10.1093/ajcp/aqz088}, pmid = {31305879}, issn = {1943-7722}, mesh = {Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/pathology ; Carcinoma, Lobular/mortality/pathology ; *Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphocytes, Tumor-Infiltrating/*pathology ; Prognosis ; Reproducibility of Results ; Stromal Cells/*pathology ; Triple Negative Breast Neoplasms/mortality/pathology ; }, abstract = {OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer.

METHODS: We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups.

RESULTS: TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance.

CONCLUSIONS: Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.}, } @article {pmid31300357, year = {2020}, author = {Son, MJ and Kim, S and Jung, HK and Ko, KH and Koh, JE and Park, AY}, title = {Can Ultrasonographic Vascular and Elastographic Features of Invasive Ductal Breast Carcinoma Predict Histologic Aggressiveness?.}, journal = {Academic radiology}, volume = {27}, number = {4}, pages = {487-496}, doi = {10.1016/j.acra.2019.06.009}, pmid = {31300357}, issn = {1878-4046}, mesh = {Axilla ; *Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal, Breast/diagnostic imaging ; *Elasticity Imaging Techniques ; Humans ; Receptors, Estrogen ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: To investigate if preoperative ultrasonographic vascular and shear-wave elastographic examinations can predict histologic aggressiveness.

MATERIALS AND METHODS: Preoperative ultrasonographic vascular features and shear-wave elasticities were retrospectively evaluated for 147 invasive ductal carcinomas. Vascular feature was assessed using four-tier vascularity score. Mean and maximum elasticities (Emean and Emax), and the lesion-to-fat ratio (Eratio) were documented. Histologic parameters were reviewed for tumor size, multiplicity, axillary lymph node status, lymphovascular invasion, histologic grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor2 (HER2), Ki-67, p53, and histologic subtype. Vascularity score and elasticities were correlated with histologic parameters and histologic parameters were compared between the group with low vascularity score and elasticities and the group with high vascularity score and elasticities using ANOVA, chi-squared test, and regression analysis.

RESULTS: Vascularity score was independently associated with tumor size (p = 0.010) and HER2 (p = 0.007). Emean and Emax were associated with tumor size, histologic grade, and lymphovascular invasion, and Eratio was associated with tumor size, histologic grade, estrogen receptor, progesterone receptor, Ki-67, and histologic subtype (p < 0.05). Emean and Emax were independently associated with tumor size (p < 0.001). The group with high vascularity score and Eratio showed large tumor size (p < 0.001) and HER2 positivity (p = 0.039) in comparison to the group with low vascularity score and Eratio.

CONCLUSION: Ultrasonographic vascular features were associated with tumor size and HER2. SWE elasticities were associated with tumor size, histologic grade, hormonal receptor, and histologic subtype. Therefore, preoperative vascular and elastographic examinations could predict histologic aggressiveness of invasive ductal breast carcinoma.}, } @article {pmid31300213, year = {2020}, author = {Mendoza Arnau, I and Sánchez Sánchez, R and Culiáñez Casas, M and Rebollo Aguirre, ÁC and González Jiménez, AD and Martínez Meca, S}, title = {Surgical clips vs. iodine-125 (125I) seeds for marking the location of nonpalpable malignant breast lesions: preliminary results.}, journal = {Radiologia}, volume = {62}, number = {1}, pages = {38-45}, doi = {10.1016/j.rx.2019.05.005}, pmid = {31300213}, issn = {2173-5107}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Female ; *Fiducial Markers ; Humans ; *Iodine Radioisotopes ; *Mammography ; Margins of Excision ; Middle Aged ; Prospective Studies ; Radiography, Interventional/methods ; *Surgical Instruments ; Ultrasonography, Interventional/methods ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVES: To assess the usefulness of iodine-125 (125I) seeds as an alternative to surgical clips for marking the location of nonpalpable malignant breast lesions for surgery.

MATERIAL AND METHODS: We included patients with histologically confirmed nonpalpable malignant lesions treated by surgery in 2015 or 2016. Patients were randomly assigned to presurgical marking with metallic clips (Group A) or with 125I seeds (Group B). In both groups, marking was guided by ultrasound and/or mammography depending on the radiologic characteristics of the lesion. During surgery, a gamma probe was used and afterward the presence of seeds in the surgical specimen was checked radiologically. In the histological analysis, the absence of tumor in the stain was considered free margins. We analyzed the following variables: age, lesion characteristics (laterality, mean size on MRI and in the surgical specimen, radiological type), and presence/absence of free margins.

RESULTS: In Group A (n=53), the most common histologic subtypes were infiltrating ductal carcinoma (IDC, 84.9%) and luminal A (LA, 49.1%); the mean size of the lesions was 1.8cm. In Group B (n=45), the most common histologic subtypes were IDC (82.2%) and LA (46.5%); the mean size of the lesions was 1.5cm. In Group A, 13.2% had involved margins and 13.2% underwent a second surgical intervention. In Group, B 11.4% had involved margins and 7.5% underwent a second surgical intervention. The differences between groups were not significant (p=0.7 for involved margins and p=0.5 for reintervention). The volume of the surgical specimens was significantly lower in Group B than in Group A (128.68cm3 vs. 189.37cm3; p<0.05).

CONCLUSIONS: Using 125I seeds was feasible and enabled significantly smaller surgical specimens than using metallic clips.}, } @article {pmid31299411, year = {2019}, author = {Molina, J and Noguer, M and Lepe, JA and Pérez-Moreno, MA and Aguilar-Guisado, M and Lasso de la Vega, R and Peñalva, G and Crespo-Rivas, JC and Gil-Navarro, MV and Salvador, J and Cisneros, JM}, title = {Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis.}, journal = {The Journal of infection}, volume = {79}, number = {3}, pages = {206-211}, doi = {10.1016/j.jinf.2019.07.002}, pmid = {31299411}, issn = {1532-2742}, mesh = {*Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Communicable Diseases/drug therapy/*epidemiology/etiology ; Drug Utilization/statistics & numerical data ; Female ; Health Plan Implementation ; Humans ; Male ; Neoplasms/complications/*epidemiology ; *Referral and Consultation ; Time Factors ; }, abstract = {OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.

METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.

RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p < 0.01; -8.1% annual reduction for 30-day mortality, p = 0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p = 0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p = 0.71; change in slope -1.98 DDD per quarter, p < 0.01). The decreasing trend for mortality before the ASP also continued after its implementation.

CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.}, } @article {pmid31291711, year = {2020}, author = {Xu, Q and Shao, Y and Zhang, J and Zhang, H and Zhao, Y and Liu, X and Guo, Z and Chong, W and Gu, F and Ma, Y}, title = {Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.}, journal = {Cancer research and treatment}, volume = {52}, number = {1}, pages = {218-245}, pmid = {31291711}, issn = {2005-9256}, support = {81572851//National Scientific Foundation of China/ ; 81672636//National Scientific Foundation of China/ ; }, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality ; Carrier Proteins/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Disease Susceptibility ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Proteins/*genetics ; Prognosis ; Recurrence ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.

MATERIALS AND METHODS: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.

RESULTS: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.

CONCLUSION: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.}, } @article {pmid31289308, year = {2019}, author = {Kole, AJ and Park, HS and Johnson, SB and Kelly, JR and Moran, MS and Patel, AA}, title = {Overall survival is improved when DCIS accompanies invasive breast cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {9934}, pmid = {31289308}, issn = {2045-2322}, support = {R01 CA197486/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*mortality/pathology/therapy ; Carcinoma, Lobular/*mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {Invasive ductal carcinoma (IDC) often presents alone or with a co-existing ductal carcinoma in situ component (IDC + DCIS). Studies have suggested that pure IDC may exhibit different biological behavior than IDC + DCIS, but whether this translates to a difference in outcomes is unclear. Here, utilizing the National Cancer Database we identified 494,801 stage I-III breast cancer patients diagnosed with either IDC alone or IDC + DCIS. We found that IDC + DCIS was associated with significantly better overall survival (OS) compared to IDC alone (5-year OS, 89.3% vs. 85.5%, p < 0.001), and this finding persisted on multivariable Cox modeling adjusting for demographic, clinical, and treatment-related variables. The significantly superior OS observed for IDC + DCIS was limited to patients with invasive tumor size < 4 cm or with node negative disease. A greater improvement in OS was observed for tumors containing ≥25% DCIS component. We also found IDC + DCIS to be associated with lower T/N stage, low/intermediate grade, ER/PR positivity, and receipt of mastectomy. Thus, the presence of a DCIS component in patients with IDC is associated with favorable clinical characteristics and independently predicts improved OS. IDC + DCIS could be a useful prognostic factor for patients with breast cancer, particularly if treatment de-escalation is being considered for small or node negative tumors.}, } @article {pmid31288210, year = {2019}, author = {Shelef, L and Klomek, AB and Fruchter, E and Kedem, R and Mann, JJ and Zalsman, G}, title = {Suicide ideation severity is associated with severe suicide attempts in a military setting.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {61}, number = {}, pages = {49-55}, doi = {10.1016/j.eurpsy.2019.06.005}, pmid = {31288210}, issn = {1778-3585}, mesh = {Adult ; Female ; Humans ; Intention ; Male ; Middle Aged ; Military Personnel/*psychology ; Risk Factors ; Self Report ; Self-Control/*psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Suicide, Attempted/psychology ; Veterans/*psychology ; Young Adult ; }, abstract = {BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.

METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n = 14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).

RESULTS: Seven items from the SSI (p = 0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.

CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.}, } @article {pmid31284267, year = {2019}, author = {Liu, S and Wei, H and Li, Y and Diao, L and Lian, R and Zhang, X and Zeng, Y}, title = {Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure.}, journal = {Reproduction (Cambridge, England)}, volume = {158}, number = {3}, pages = {247-255}, doi = {10.1530/REP-19-0172}, pmid = {31284267}, issn = {1741-7899}, mesh = {Abortion, Habitual/*immunology/metabolism ; Adult ; Cell Differentiation ; Dendritic Cells/immunology/*metabolism ; Embryo Implantation/*immunology ; Female ; Humans ; Interleukin-10/*metabolism ; Interleukin-6/metabolism ; Pregnancy ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.}, } @article {pmid31283940, year = {2019}, author = {Klepac, K and Georgiadi, A and Tschöp, M and Herzig, S}, title = {The role of brown and beige adipose tissue in glycaemic control.}, journal = {Molecular aspects of medicine}, volume = {68}, number = {}, pages = {90-100}, doi = {10.1016/j.mam.2019.07.001}, pmid = {31283940}, issn = {1872-9452}, mesh = {Adipose Tissue, Beige/*metabolism ; Adipose Tissue, Brown/*metabolism ; Animals ; Energy Metabolism ; Glucose/metabolism ; Humans ; Hyperglycemia/*pathology ; Signal Transduction ; }, abstract = {For the past decade, brown adipose tissue (BAT) has been extensively studied as a potential therapy for obesity and metabolic diseases due to its thermogenic and glucose-consuming properties. It is now clear that the function of BAT goes beyond heat production, as it also plays an important endocrine role by secreting the so-called batokines to communicate with other metabolic tissues and regulate systemic energy homeostasis. However, despite numerous studies showing the benefits of BAT in rodents, it is still not clear whether recruitment of BAT can be utilized to treat human patients. Here, we review the advances on understanding the role of BAT in metabolism and its benefits on glucose and lipid homeostasis in both humans and rodents. Moreover, we discuss the latest methodological approaches to assess the contribution of BAT to human metabolism as well as the possibility to target BAT, pharmacologically or by lifestyle adaptations, to treat metabolic disorders.}, } @article {pmid31281731, year = {2019}, author = {Qiu, R and Zhao, W and Yang, J and Shen, Y and Wang, B and Li, P and Zhao, A and Tian, Q and Zhang, M and Yi, M and Yang, J and Dong, D}, title = {Comparative Analysis of Outcomes and Clinicopathological Characteristics of Synchronous and Metachronous Contralateral Breast Cancer: A Study of the SEER Database.}, journal = {Journal of breast cancer}, volume = {22}, number = {2}, pages = {297-310}, pmid = {31281731}, issn = {1738-6756}, abstract = {PURPOSE: Numerous previous studies have reported inconsistent results about the differences between synchronous contralateral breast cancer (sCBC) and metachronous contralateral breast cancer (mCBC). This study aimed to compare the clinical characteristics and outcomes between sCBC and mCBC and determine predictive factors for the survival of sCBC and mCBC patients.

METHODS: Using the Surveillance, Epidemiology, and End Results Program database, we identified sCBC or mCBC patients from 2000 to 2010. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to analyze overall survival and breast cancer-specific survival (BCSS) rates of sCBCs and mCBCs, respectively.

RESULTS: Overall, 14,057 sCBC (n = 8,139, 57.9%) and mCBC (n = 5,918, 42.1%) patients were included. The first tumors of sCBC were more likely to have higher stage and more lymph and distant metastases, whereas those of mCBC were more often infiltrating ductal carcinoma (IDC), had localized stage, were estrogen receptor (ER) and progesterone receptor (PR) negative, and had less axillary nodal involvement. The second tumors of mCBC tended to be IDC and have higher grade, adverse stage, ER and PR-negativity; and more axillary nodal involvement, compared to the second tumors of sCBC. mCBC patients had significantly favorable 5-year BCSS but worse long-term BCSS compared with sCBC patients. Moreover, subgroup analysis revealed no significant difference of BCSS between sCBC and mCBC among patients aged 18-60 years. Multivariate analysis indicated that age, grade, and stage of 2 tumors; surgery for second tumor; and ER status of the second tumor were independent prognostic factors for BCSS of contralateral breast cancer (CBC).

CONCLUSION: The characteristics and outcomes of sCBCs and mCBCs were substantially different. sCBC and mCBC patients may have different prognosis, and the prognosis of CBC depends on the first and second tumors.}, } @article {pmid31281724, year = {2019}, author = {Eras, N and Daloglu, FT and Çolak, T and Guler, M and Akbas, E}, title = {The Correlation between IL-1β-C31T Gene Polymorphism and Susceptibility to Breast Cancer.}, journal = {Journal of breast cancer}, volume = {22}, number = {2}, pages = {210-218}, pmid = {31281724}, issn = {1738-6756}, abstract = {PURPOSE: Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been shown to influence breast cancer susceptibility. The relationship between its risk of breast cancer and IL-1β-C31T polymorphism has been demonstrated, but the results remain controversial. Therefore, our study aimed to investigate the correlation between the IL-1β-C31T gene polymorphism and susceptibility to breast cancer.

METHODS: The genotype frequencies of IL-1β-C31T polymorphism were compared between 204 breast cancer cases and 210 controls using polymerase chain reaction and restriction fragment length polymorphism techinques. Further multivariate binary logistic regression analyses were used to assess the association between IL-1β-C31T polymorphism and breast cancer risk.

RESULTS: The frequency of the T allele of IL-1β-C31T polymorphism in breast cancer cases was significantly higher than that in the controls (56.1% vs. 47.9%). The frequencies of genotypes CC, CT, and TT in the cases were 22.1%, 43.6%, and 34.3%, respectively, while in the control group they were 24.3%, 55.7%, and 20.0%, respectively. There was a significant difference between the prevalence of TT genotype in the 2 groups (adjusted odds ratio [OR], 2.06; 95% confidence interval [CI], 1.16-3.66; p  =  0.014). Breast cancer risk increased in women with TT genotype, body mass index (BMI) ≥ 25 kg/m[2] (OR, 2.19; 95% CI, 1.09-4.36), late age at first birth (OR, 2.43; 95% CI, 1.29-4.56), postmenopausal status (OR, 3.15; 95% CI, 1.39-7.16), and negative smoking history (OR, 2.52; 95% CI, 1.32-4.82). Furthermore, increase in breast cancer risk among women diagnosed with invasive ductal carcinoma was associated with CT/TT genotypes (OR, 2.82; 95% CI, 1.38-5.76).

CONCLUSION: The IL-1β-C31T polymorphism affects breast cancer susceptibility, especially in women with late age at first birth, high BMI, postmenopausal status, negative smoking history, and invasive ductal carcinoma. Our study adds to the evidence about the importance of IL-1β-C31T polymorphism in breast cancer susceptibility.}, } @article {pmid31275451, year = {2019}, author = {Simeunovic, D and Odanovic, N and Pljesa-Ercegovac, M and Radic, T and Radovanovic, S and Coric, V and Milinkovic, I and Matic, M and Djukic, T and Ristic, A and Risimic, D and Seferovic, P and Simic, T and Simic, D and Savic-Radojevic, A}, title = {Glutathione Transferase P1 Polymorphism Might Be a Risk Determinant in Heart Failure.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {6984845}, pmid = {31275451}, issn = {1875-8630}, mesh = {Aged ; Cardiomyopathy, Dilated/complications/*genetics ; Coronary Artery Disease/complications/*genetics ; Female ; Glutathione S-Transferase pi/*genetics ; Heart Failure/etiology/*genetics ; Humans ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; }, abstract = {Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.}, } @article {pmid31263748, year = {2019}, author = {Levine, KM and Priedigkeit, N and Basudan, A and Tasdemir, N and Sikora, MJ and Sokol, ES and Hartmaier, RJ and Ding, K and Ahmad, NZ and Watters, RJ and Weiss, KR and Blohmer, JU and Denkert, C and Machleidt, A and Karsten, MM and Boisen, MM and Elishaev, E and Lucas, PC and Lee, AV and Oesterreich, S}, title = {FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype.}, journal = {NPJ breast cancer}, volume = {5}, number = {}, pages = {19}, pmid = {31263748}, issn = {2374-4677}, support = {R01 CA224909/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; T32 GM008208/GM/NIGMS NIH HHS/United States ; F30 CA203095/CA/NCI NIH HHS/United States ; }, abstract = {Invasive lobular carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. To study acquired resistance to endocrine therapy in ILC, we have recently performed RNA-Sequencing on long-term estrogen deprived cell lines and identified FGFR4 overexpression as a top druggable target. Here, we show that FGFR4 expression also increases dramatically in endocrine-treated distant metastases, with an average fold change of 4.8 relative to the paired primary breast tumor for ILC, and 2.4-fold for invasive ductal carcinoma (IDC). In addition, we now report that FGFR4 hotspot mutations are enriched in metastatic breast cancer, with an additional enrichment for ILC, suggesting a multimodal selection of FGFR4 activation. These data collectively support the notion that FGFR4 is an important mediator of endocrine resistance in ILC, warranting future mechanistic studies on downstream signaling of overexpressed wild-type and mutant FGFR4.}, } @article {pmid31259153, year = {2019}, author = {Xie, T and Wang, Z and Zhao, Q and Bai, Q and Zhou, X and Gu, Y and Peng, W and Wang, H}, title = {Machine Learning-Based Analysis of MR Multiparametric Radiomics for the Subtype Classification of Breast Cancer.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {505}, pmid = {31259153}, issn = {2234-943X}, abstract = {Objective: To investigate whether machine learning analysis of multiparametric MR radiomics can help classify immunohistochemical (IHC) subtypes of breast cancer. Study design: One hundred and thirty-four consecutive patients with pathologically-proven invasive ductal carcinoma were retrospectively analyzed. A total of 2,498 features were extracted from the DCE and DWI images, together with the new calculated images, including DCE images changing over six time points (DCEsequential) and DWI images changing over three b-values (DWIsequential). We proposed a novel two-stage feature selection method combining traditional statistics and machine learning-based methods. The accuracies of the 4-IHC classification and triple negative (TN) vs. non-TN cancers were assessed. Results: For the 4-IHC classification task, the best accuracy of 72.4% was achieved based on linear discriminant analysis (LDA) or subspace discrimination of assembled learning in conjunction with 20 selected features, and only small dependent emphasis of Kendall-tau-b for sequential features, based on the DWIsequential with the LDA model, yielding an accuracy of 53.7%. The linear support vector machine (SVM) and medium k-nearest neighbor using eight features yielded the highest accuracy of 91.0% for comparing TN to non-TN cancers, and the maximum variance for DWIsequential alone, together with a linear SVM model, achieved an accuracy of 83.6%. Conclusions: Whole-tumor radiomics on MR multiparametric images, DCE images changing over time points, and DWI images changing over different b-values provide a non-invasive analytical approach for breast cancer subtype classification and TN cancer identification.}, } @article {pmid31258788, year = {2019}, author = {Huang, L and Ji, H and Yin, L and Niu, X and Wang, Y and Liu, Y and Xuan, Q and Li, L and Zhang, H and Zhou, X and Li, J and Cui, C and Yang, Y and An, W and Zhang, Q}, title = {High Expression of Plakoglobin Promotes Metastasis in Invasive Micropapillary Carcinoma of the Breast via Tumor Cluster Formation.}, journal = {Journal of Cancer}, volume = {10}, number = {12}, pages = {2800-2810}, pmid = {31258788}, issn = {1837-9664}, abstract = {Invasive micropapillary carcinoma of the breast (IMPC) is a rare subtype of breast cancer that has a high frequency of lymph node (LN) involvement and metastasis to distant organs. IMPC is characterized by distinct histomorphology and unfavorable prognosis when compared with invasive ductal carcinoma no special type (IDC-NST). However, the underlying molecular mechanisms remain unclear. We reported here that plakoglobin, as a key component in cell adhesion, can promote collective metastasis through facilitating IMPC clusters formation. In comparing the clinicopathological features of 451 IMPC patients and 282 IDC-NST patients, our results showed that tumor emboli were significantly higher in IMPC patients and were associated with a high frequency of metastasis. Both in vitro and in vivo data showed overexpression of plakoglobin in both the cell membrane and the cytoplasm of IMPC clusters. When plakoglobin was knocked down in IMPC cell models, the tumor cell clusters were depolymerized. Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells in vivo. Further analysis showed that higher expression of plakoglobin was able to promote activation of the PI3K/Akt/Bcl-2 pathway, which might protect the clusters from anoikis. Our data indicate that plakoglobin promotes tumor cluster formation in IMPC and downregulates apoptosis in the cell clusters through activation of PI3K/Akt/Bcl-2 signaling. These results provide a convincing rationale for the high metastatic propensity seen in IMPC.}, } @article {pmid31256281, year = {2019}, author = {D'Iorio, A and Maggi, G and Vitale, C and Amboni, M and Di Meglio, D and Trojano, L and Santangelo, G}, title = {Prospective memory in Parkinson's disease: the role of the motor subtypes.}, journal = {Journal of neurology}, volume = {266}, number = {10}, pages = {2505-2511}, pmid = {31256281}, issn = {1432-1459}, mesh = {Aged ; Cognitive Dysfunction/etiology/*physiopathology ; Executive Function/physiology ; Female ; Humans ; Hypokinesia/etiology/*physiopathology ; Male ; *Memory, Episodic ; Middle Aged ; Muscle Rigidity/etiology/*physiopathology ; Parkinson Disease/classification/complications/*physiopathology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM.

METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances.

RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD.

CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.}, } @article {pmid31250071, year = {2019}, author = {Albrecht, W and Kappenberg, F and Brecklinghaus, T and Stoeber, R and Marchan, R and Zhang, M and Ebbert, K and Kirschner, H and Grinberg, M and Leist, M and Moritz, W and Cadenas, C and Ghallab, A and Reinders, J and Vartak, N and van Thriel, C and Golka, K and Tolosa, L and Castell, JV and Damm, G and Seehofer, D and Lampen, A and Braeuning, A and Buhrke, T and Behr, AC and Oberemm, A and Gu, X and Kittana, N and van de Water, B and Kreiling, R and Fayyaz, S and van Aerts, L and Smedsrød, B and Ellinger-Ziegelbauer, H and Steger-Hartmann, T and Gundert-Remy, U and Zeigerer, A and Ullrich, A and Runge, D and Lee, SML and Schiergens, TS and Kuepfer, L and Aguayo-Orozco, A and Sachinidis, A and Edlund, K and Gardner, I and Rahnenführer, J and Hengstler, JG}, title = {Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations.}, journal = {Archives of toxicology}, volume = {93}, number = {6}, pages = {1609-1637}, pmid = {31250071}, issn = {1432-0738}, support = {031L0045//BMBF/International ; 031LO119//BMBF/International ; 01EK1604A//BMBF/International ; 031L0021A//BMBF/International ; 681002//EU/International ; 116030//EU/International ; CP16/00097//European Regional Development Fund/International ; }, mesh = {Administration, Oral ; Algorithms ; Animals ; Cell Line ; Cell Survival/drug effects ; Chemical and Drug Induced Liver Injury/*diagnosis ; Computer Simulation ; Drug-Related Side Effects and Adverse Reactions/*diagnosis ; Gene Expression/drug effects ; Hepatocytes/drug effects ; Humans ; In Vitro Techniques ; Maximum Tolerated Dose ; Pharmaceutical Preparations/administration & dosage/blood ; Pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; Support Vector Machine ; }, abstract = {Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity.}, } @article {pmid31244288, year = {2019}, author = {Ghaderi, F and Mehdipour, F and Hosseini, A and Talei, A and Ghaderi, A}, title = {Establishment and Characterization of a New Triple Negative Breast Cancer Cell Line from an Iranian Breast Cancer Tissue.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {6}, pages = {1683-1689}, pmid = {31244288}, issn = {2476-762X}, mesh = {Adult ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Culture Techniques ; Cell Line, Tumor ; *Cell Movement ; *Cell Proliferation ; *Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Triple Negative Breast Neoplasms/metabolism/*pathology ; }, abstract = {Breast cancer is the most common malignancy and the leading cause of cancer-related death among women worldwide. The underlying mechanisms for breast cancer development, especially in young women, are not completely understood. Although there are several experimental models to understand the biology of breast cancer such as immortalized cell lines, many of these cell lines have been in culture for decades and most of them have been derived from Caucasians or African-Americans. So, it is required to establish a new cell line derived from primary tumors and Asian women. In this study Pari-Institute for Cancer Research (Pari-ICR) was derived from the primary breast tumor of a 36-years old patient with invasive ductal carcinoma. We characterized the cell line by examining morphology, expression of different markers, and functional profile. Immunocytochemistry showed that this cell line does not express estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2). Pari-ICR cell line expresses high levels of Vimentin, Ezrin, and S100 but does not express EpCAM, Cytokeratin19, Pan-cytokeratin, Nestin, and Desmin. Its doubling time of Pari-ICR was about 22h and was able to grow as colonies in soft agar. It displayed a higher ability of migration and invasion in comparison with MCF-7 cell line. This breast cancer cell line can serve as a model for understanding the molecular mechanisms of breast carcinogenesis. Moreover, it can be used as an appropriate resource to find novel biomarkers or assess new drugs.}, } @article {pmid31243309, year = {2019}, author = {Zwarts, I and van Zutphen, T and Kruit, JK and Liu, W and Oosterveer, MH and Verkade, HJ and Uhlenhaut, NH and Jonker, JW}, title = {Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {9299}, pmid = {31243309}, issn = {2045-2322}, mesh = {Adipose Tissue/metabolism ; Animals ; Diet ; Duodenum/metabolism ; Fructose/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Glucose Transporter Type 5/*metabolism ; HEK293 Cells ; Haplorhini ; Humans ; Hydrocarbons, Fluorinated/pharmacology ; Ligands ; Liver X Receptors/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Response Elements ; Sulfonamides/pharmacology ; Transcription, Genetic ; }, abstract = {Fructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at -385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.}, } @article {pmid31240968, year = {2021}, author = {Shenkman, G and Pardo Aviv, L and Hain, D and Goren, O and Shapira, S and Nakash, O and Brunstein Klomek, A and Berant, E}, title = {The moderation of attachment in the association between depressive symptoms and self-harm among a clinical sample.}, journal = {Journal of mental health (Abingdon, England)}, volume = {30}, number = {1}, pages = {58-65}, doi = {10.1080/09638237.2019.1630723}, pmid = {31240968}, issn = {1360-0567}, mesh = {Anxiety/epidemiology ; Anxiety Disorders ; *Depression/epidemiology ; Humans ; Object Attachment ; *Self-Injurious Behavior/epidemiology ; }, abstract = {BACKGROUND: Self-harm is a severe health problem worldwide and in particular in clinical settings. The association of depression and self-harm has been extensively studied alongside various variables that have been examined as moderating this association. However, no previous study has examined the moderating role of attachment in this association.

AIM: We explored the role of attachment orientation in moderating the association between depressive symptoms and self-harm among a sample of patients in a community mental health clinic.

METHOD: This study was a de-identified archival study of patients' medical charts, and used a convenience sample of 199 patients, which completed self-report measures following the initial intake appointment as part of clinic procedures.

RESULTS: Findings showed that both attachment anxiety and avoidance moderated the association between depressive symptoms and self-harm, such that depressive symptoms were positively associated with self-harm only when attachment anxiety scores were high, and attachment avoidance scores were high or average.

CONCLUSIONS: Attachment anxiety and avoidance should be assessed in the initial intake of patients as it has a contribution to understanding self-harm vulnerability among new patients. Future studies should explore this moderation longitudinally so causality could be inferred.}, } @article {pmid31239068, year = {2019}, author = {Thomas, M and Kelly, ED and Abraham, J and Kruse, M}, title = {Invasive lobular breast cancer: A review of pathogenesis, diagnosis, management, and future directions of early stage disease.}, journal = {Seminars in oncology}, volume = {46}, number = {2}, pages = {121-132}, doi = {10.1053/j.seminoncol.2019.03.002}, pmid = {31239068}, issn = {1532-8708}, mesh = {Breast Neoplasms/diagnosis/pathology/*therapy ; Carcinoma, Lobular/diagnosis/pathology/*therapy ; *Disease Management ; Female ; Humans ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer after invasive ductal carcinoma (IDC). Invasive lobular carcinoma has unique clinical, pathologic, and radiographic features which suggest that it is a distinct clinical entity; however, it is treated with the same treatment paradigms as IDC. Information regarding the specific treatment of ILC, including response to standard therapy, is sparse. Neoadjuvant treatment considerations are of great importance in this space as ILC is often found at a locally advanced stage. In this review, we summarize the classic features of ILC and the available data regarding efficacy of both endocrine therapy and chemotherapy in curative treatment of breast cancer.}, } @article {pmid31238731, year = {2019}, author = {Farsang, A and Bódi, I and Fölker, O and Minkó, K and Benyeda, Z and Bálint, Á and Oláh, I}, title = {Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.}, journal = {Acta veterinaria Hungarica}, volume = {67}, number = {2}, pages = {183-196}, doi = {10.1556/004.2019.020}, pmid = {31238731}, issn = {0236-6290}, mesh = {Animals ; Avian Proteins/metabolism ; Cecum/*immunology ; *Chickens ; Coronavirus Infections/metabolism/*veterinary ; Dendritic Cells/*metabolism ; Gammacoronavirus/physiology ; Mannose-Binding Lectins/*metabolism ; Poultry Diseases/*metabolism ; Specific Pathogen-Free Organisms ; Spleen/*immunology ; }, abstract = {The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.}, } @article {pmid31229512, year = {2019}, author = {Cao, L and Basudan, A and Sikora, MJ and Bahreini, A and Tasdemir, N and Levine, KM and Jankowitz, RC and McAuliffe, PF and Dabbs, D and Haupt, S and Haupt, Y and Lucas, PC and Lee, AV and Oesterreich, S and Atkinson, JM}, title = {Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.}, journal = {Cancer letters}, volume = {461}, number = {}, pages = {21-30}, pmid = {31229512}, issn = {1872-7980}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Cycle Checkpoints ; Cell Cycle Proteins/*genetics/metabolism ; Cell Proliferation ; DNA Copy Number Variations ; Estrogen Receptor alpha/*genetics ; Female ; Follow-Up Studies ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Survival Rate ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). To identify potential genetic drivers of ILC progression, we used NanoString nCounter technology to investigate the DNA copy number (CN) in 70 well-curated primary ILC samples. We confirmed prior observations of frequent amplification of CCND1 (33%), and MYC (17%) in ILC, but additionally identified a substantial subset of ILCs with ESR1 and ERBB2 (19%) amplifications. Of interest, tumors with ESR1 CN gains (14%) and amplification (10%) were more likely to recur compared to those with normal CN. Finally, we observed that MDM4 (MDMX) was amplified in 17% of ILC samples. MDM4 knockdown in TP53 wild-type ILC cell lines caused increased apoptosis, decreased proliferation associated with cell cycle arrest, and concomitant activation of TP53 target genes. Similar effects were seen in TP53 mutant cells, indicting a TP53-independent role for MDM4 in ILC. To conclude, amplification of ESR1 and MDM4 are potential genetic drivers of ILC. These amplifications may represent actionable, targetable tumor dependencies, and thus have potential clinical implications and warrant further study.}, } @article {pmid31226865, year = {2019}, author = {Chishti, N and Jagwani, S and Dhamecha, D and Jalalpure, S and Dehghan, MH}, title = {Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {55}, number = {6}, pages = {}, pmid = {31226865}, issn = {1648-9144}, mesh = {Antineoplastic Agents/*administration & dosage/therapeutic use ; Docetaxel/*administration & dosage/therapeutic use ; Humans ; Lung Neoplasms/*drug therapy ; Nanoparticles/*administration & dosage/therapeutic use ; Poloxamer/administration & dosage/therapeutic use ; Treatment Outcome ; }, abstract = {Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around -36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).}, } @article {pmid31222554, year = {2019}, author = {Arya, BK and Bhattacharya, SD and Harigovind, G and Das, RS and Khan, T and Ganaie, F and Niyogi, SK and Ravikumar, KL and Manoharan, A and Bhattacharyya, S and Panda, S and Mandal, S and Acharya, B}, title = {Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.}, journal = {Indian journal of pediatrics}, volume = {86}, number = {11}, pages = {1002-1010}, pmid = {31222554}, issn = {0973-7693}, support = {Fulbright-Nehru Doctoral Research Award 2014-15//United States Department of State's Bureau of Educational and Cultural Affairs, and USIEF, New Delhi/International ; 5/7/463/2010-RHN//Indian Council of Medical Research/International ; }, mesh = {Carrier State/*microbiology ; Child ; Child, Preschool ; Female ; HIV Infections/*complications/epidemiology/microbiology ; Humans ; India ; Longitudinal Studies ; Male ; Microbial Sensitivity Tests ; Nasopharynx/microbiology ; Parents ; Pneumococcal Infections/epidemiology/*microbiology/transmission/virology ; Pneumococcal Vaccines/*administration & dosage ; Prevalence ; Prospective Studies ; Serogroup ; Serotyping ; Streptococcus pneumoniae/immunology/*pathogenicity ; Vaccination ; }, abstract = {OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families.

METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method.

RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p = 0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR = 1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p = 0.02).

CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.}, } @article {pmid31217350, year = {2019}, author = {Lodd, E and Wiggenhauser, LM and Morgenstern, J and Fleming, TH and Poschet, G and Büttner, M and Tabler, CT and Wohlfart, DP and Nawroth, PP and Kroll, J}, title = {The combination of loss of glyoxalase1 and obesity results in hyperglycemia.}, journal = {JCI insight}, volume = {4}, number = {12}, pages = {}, pmid = {31217350}, issn = {2379-3708}, mesh = {Animals ; CRISPR-Cas Systems ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/genetics ; Diet ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Predisposition to Disease ; Glucose/metabolism ; Hyperglycemia/*etiology/genetics ; Insulin Resistance ; Lactoylglutathione Lyase/genetics/*physiology ; Liver/metabolism ; Male ; Obesity/*complications ; Pyruvaldehyde/metabolism ; Retina/pathology ; Zebrafish/growth & development ; }, abstract = {The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.}, } @article {pmid31210440, year = {2019}, author = {Saleh Gargari, S and Taheri, M and Kholghi Oskooei, V and Omrani, MD and Ghafouri-Fard, S}, title = {Transcription Levels of nicotinamide nucleotide transhydrogenase and Its Antisense in Breast Cancer Samples.}, journal = {Cell journal}, volume = {21}, number = {3}, pages = {331-336}, pmid = {31210440}, issn = {2228-5806}, abstract = {OBJECTIVE: To evaluate association of patients' clinicopathological data with expression of nicotinamide nucleotide transhydrogenase (NNT) and naturally occurring antisense RNA of the same gene locus (NNT-AS1) in breast cancer samples.

MATERIALS AND METHODS: In the current case-control study, mean expressions of NNT and NNT-AS1 were assessed in 108 breast tissue samples including 54 invasive ductal carcinoma samples and 54 adjacent non-cancerous tissues (ANCTs) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTS: NNT expression was not significantly different between tumor tissues and ANCTs. However, NNT-AS1 expression was significantly down-regulated in tumor tissues compared to ANCTs (expression ratio=0.51, P=0.01). NNT-AS1 expression was significantly higher in estrogen receptor (ER) negative samples, in comparison with ER positives (P=0.01). No considerable difference was found in the gene expressions between other subcategories of patients. Considerable correlations were detected between expression levels of these two genetic loci in both tumor tissues and ANCTs.

CONCLUSION: In the current study, for the first time we simultaneously assessed expression of NNT and NNT-AS1 in breast cancer tissues. This study highlights association of ER status with dysregulation of NNT-AS1 in breast cancer tissues. Future researches are necessary to explore the function of this long non-coding RNA (lncRNA) in the pathogenesis of breast cancer.}, } @article {pmid31205152, year = {2019}, author = {Blanc-Durand, P and Milliner, M and Huchet, V and Luciani, A and Itti, E}, title = {18F-FDG Whole-body PET/MRI of a 30-Week Pregnant Woman With Breast Cancer Revealed Interesting Fetal Findings.}, journal = {Clinical nuclear medicine}, volume = {44}, number = {10}, pages = {818-820}, doi = {10.1097/RLU.0000000000002663}, pmid = {31205152}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology/therapy ; Female ; Fetus/*diagnostic imaging ; *Fluorodeoxyglucose F18 ; Humans ; *Magnetic Resonance Imaging ; *Multimodal Imaging ; Neoadjuvant Therapy ; Neoplasm Staging ; *Positron-Emission Tomography ; Pregnancy ; *Whole Body Imaging ; }, abstract = {A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of neoadjuvant chemotherapy.}, } @article {pmid31203172, year = {2019}, author = {Raetz, AG and David, SS}, title = {When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.}, journal = {DNA repair}, volume = {80}, number = {}, pages = {16-25}, pmid = {31203172}, issn = {1568-7856}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; R29 CA067985/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA/metabolism ; *DNA Damage ; DNA Glycosylases/*metabolism ; *DNA Repair ; Guanine/analogs & derivatives/metabolism ; Humans ; Neoplasms/genetics/*metabolism ; *Signal Transduction ; }, abstract = {MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.}, } @article {pmid31200836, year = {2019}, author = {Jeyapala, R and Savio, AJ and Olkhov-Mitsel, E and Kamdar, S and Zhao, F and Cuizon, C and Liu, RSC and Zlotta, A and Fleshner, N and van der Kwast, T and Bapat, B}, title = {GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.}, journal = {European urology oncology}, volume = {2}, number = {3}, pages = {231-238}, doi = {10.1016/j.euo.2018.08.003}, pmid = {31200836}, issn = {2588-9311}, mesh = {Biomarkers, Tumor/genetics ; Carcinoma, Intraductal, Noninfiltrating/blood/genetics/mortality/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins/genetics ; Dioxygenases ; Epigenesis, Genetic ; Homeodomain Proteins/*genetics ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/*pathology/surgery ; Proto-Oncogene Proteins/genetics ; Recurrence ; Survival Analysis ; }, abstract = {BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.

OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.

Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.

The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.

RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.

CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.

PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.}, } @article {pmid31197906, year = {2019}, author = {Tan, QT and Mihir, AG}, title = {A case of invasive ductal carcinoma presenting as an exophytic nipple mass.}, journal = {The breast journal}, volume = {25}, number = {5}, pages = {1000-1001}, doi = {10.1111/tbj.13391}, pmid = {31197906}, issn = {1524-4741}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Mastectomy ; Nipples/*pathology ; Ultrasonography, Mammary ; }, } @article {pmid31196239, year = {2019}, author = {Sherbuk, JE and McManus, D and Topal, JE and Malinis, M}, title = {Improved mortality in Staphylococcus aureus bacteremia with the involvement of antimicrobial stewardship team and infectious disease consultation.}, journal = {Infection control and hospital epidemiology}, volume = {40}, number = {8}, pages = {932-935}, doi = {10.1017/ice.2019.136}, pmid = {31196239}, issn = {1559-6834}, mesh = {Aged ; *Antimicrobial Stewardship ; Bacteremia/*drug therapy ; Databases, Factual ; Female ; Humans ; Male ; Middle Aged ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/*drug therapy ; Staphylococcus aureus/*drug effects ; }, abstract = {A retrospective study was conducted to evaluate the value of the antimicrobial stewardship team (AST) combined with infectious diseases consultation (IDC) on management and outcomes of Staphylococcus aureus bacteremia (SAB) in a tertiary-care academic center. Involvement of AST or IDC was associated with reduced mortality of SAB.}, } @article {pmid31195104, year = {2019}, author = {Erel, H and Ronen, T and Freedman, G and Deouell, LY and Levy, DA}, title = {Preserved left and upper visual field advantages in older adults' orienting of attention.}, journal = {Experimental gerontology}, volume = {124}, number = {}, pages = {110630}, doi = {10.1016/j.exger.2019.110630}, pmid = {31195104}, issn = {1873-6815}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aging/*physiology ; *Attention ; Female ; *Functional Laterality ; Humans ; Male ; Middle Aged ; *Orientation ; Reaction Time ; Space Perception/*physiology ; *Visual Fields ; Young Adult ; }, abstract = {Lateralization of the distribution of attentional function in the brain is asserted to lead to asymmetry in attentional allocation. This is expressed in the phenomenon of pseudoneglect, in which line and object bisection judgments indicate left visual field (and presumably right hemisphere) dominance. Several studies indicate that this asymmetry is not found in old age, which is taken as an indication of decline in attentional function with aging. We examined this assertion using a more comprehensive assay of attentional asymmetry. We contrasted the spatial distribution of older and younger adults' visual attention using the Starry Night Task, a speeded visual search task in which targets must be located across a wide spatial distribution against a dynamic background of distracters. As expected, compared to younger adults, older adults' response times were longer overall. However, we found that older adults exhibited a graded left visual field advantage, even more distinctly than did younger adults. Additionally, older adults exhibited a graded upper visual field advantage equivalent to that of younger adults. These results indicate that aging may not necessarily compromise basic patterns of distribution of spatial attention. They do not support claims of aging-related loss of attentional lateralization.}, } @article {pmid31192864, year = {2019}, author = {Horimoto, Y and Terao, T and Tsutsumi, Y and Tanabe, M and Mogushi, K and Hlaing, MT and Sasaki, R and Saeki, H and Okazaki, M and Sonoue, H and Arakawa, A and Saito, M}, title = {Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.}, journal = {The American journal of surgical pathology}, volume = {43}, number = {9}, pages = {1221-1228}, doi = {10.1097/PAS.0000000000001300}, pmid = {31192864}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Female ; Gene Amplification ; Genes, erbB-2 ; Humans ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/metabolism ; }, abstract = {Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.}, } @article {pmid31192530, year = {2019}, author = {Zhang, J and Zhao, B and Jin, F}, title = {The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.}, journal = {The breast journal}, volume = {25}, number = {5}, pages = {838-847}, doi = {10.1111/tbj.13347}, pmid = {31192530}, issn = {1524-4741}, mesh = {Breast Neoplasms/*classification/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Female ; Humans ; Middle Aged ; Neoplasm Staging/*standards/statistics & numerical data ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; SEER Program ; United States ; }, abstract = {The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.}, } @article {pmid31186766, year = {2019}, author = {Zhu, L and Ma, N and Wang, B and Zhou, C and Yan, Y and Wang, K and He, J and Ren, Y}, title = {Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.}, journal = {Oncology letters}, volume = {17}, number = {6}, pages = {5469-5480}, pmid = {31186766}, issn = {1792-1074}, abstract = {The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER[+]/HER2[-] early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ[2] test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ[2] test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2-47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER[+] breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER[+] breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.}, } @article {pmid31186117, year = {2019}, author = {Cuesta Cuesta, AB and Martín Ríos, MD and Noguero Meseguer, MR and García Velasco, JA and de Matías Martínez, M and Bartolomé Sotillos, S and Abreu Griego, E}, title = {Accuracy of tumor size measurements performed by magnetic resonance, ultrasound and mammography, and their correlation with pathological size in primary breast cancer.}, journal = {Cirugia espanola}, volume = {97}, number = {7}, pages = {391-396}, doi = {10.1016/j.ciresp.2019.04.017}, pmid = {31186117}, issn = {2173-5077}, mesh = {Adult ; Age Factors ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Carcinoma in Situ/diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Mammography/methods ; Middle Aged ; Retrospective Studies ; Ultrasonography/methods ; }, abstract = {INTRODUCTION: The objective of this study was to determine which image test used to measure the size of pre-operative primary breast cancer (mammography, ultrasound or magnetic resonance imaging [MRI]) correlated best with the size of the tumor in the postoperative surgical specimen.

METHODS: A retrospective analysis was conducted of women diagnosed with breast cancer for which primary surgical treatment was indicated and who underwent surgical intervention between January 2014 and December 2016. Sociodemographic, imaging and histological variables were collected. The results are presented by age group, tumor size and histological type.

RESULTS: In the 224 women studied, mammography and MRI tumor sizes were compared with pathology study tumor measurements, revealing no significant differences, both overall and based on histologic type or age. However, both significantly underestimated large tumors and significantly overestimated small tumors. Ultrasound significantly underestimated tumor size, especially in large tumors, older patients and in infiltrating ductal carcinoma (IDC) and infiltrating ductal carcinoma with associated ductal carcinoma in situ (IDC+DCIS). MRI correlated best with histological tumor size, although with no statistically significant differences.

CONCLUSIONS: MRI is the best predictor of tumor size in breast cancer. Histologic type and tumor size are key parameters when estimating tumor size and should be taken into account when planning surgery. Patient age does not interfere with the interpretation of imaging tests.}, } @article {pmid31183578, year = {2019}, author = {Troisi, J and Landolfi, A and Vitale, C and Longo, K and Cozzolino, A and Squillante, M and Savanelli, MC and Barone, P and Amboni, M}, title = {A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {15}, number = {6}, pages = {90}, pmid = {31183578}, issn = {1573-3890}, mesh = {Aged ; Aged, 80 and over ; Biomarkers/blood/metabolism ; Case-Control Studies ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Male ; *Metabolome/drug effects ; Metabolomics ; Middle Aged ; Parkinson Disease/blood/drug therapy/*metabolism/pathology ; Pilot Projects ; }, abstract = {INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment.

OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment.

METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression.

RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment.

CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.}, } @article {pmid31182966, year = {2019}, author = {Bao, Y and Wang, L and Shi, L and Yun, F and Liu, X and Chen, Y and Chen, C and Ren, Y and Jia, Y}, title = {Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.}, journal = {Cellular & molecular biology letters}, volume = {24}, number = {}, pages = {38}, pmid = {31182966}, issn = {1689-1392}, mesh = {Breast Neoplasms/*genetics ; Down-Regulation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Sequence Analysis, RNA ; Signal Transduction/*genetics ; Transcriptome/genetics ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.

METHODS: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.

RESULTS: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.

CONCLUSION: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.}, } @article {pmid31182685, year = {2019}, author = {Arabpour, M and Ghods, A and Shariat, M and Talei, AR and Mehdipour, F and Ghaderi, A}, title = {Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.}, journal = {Iranian journal of immunology : IJI}, volume = {16}, number = {2}, pages = {108-116}, doi = {10.22034/IJI.2019.80254}, pmid = {31182685}, issn = {1735-367X}, mesh = {4-1BB Ligand/*metabolism ; Adult ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Lymphocyte Activation ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/metabolism ; Sentinel Lymph Node/*metabolism ; }, abstract = {BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.

OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.

METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry.

RESULTS: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.

CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.}, } @article {pmid31177593, year = {2019}, author = {Gilleron, J and Gerdes, JM and Zeigerer, A}, title = {Metabolic regulation through the endosomal system.}, journal = {Traffic (Copenhagen, Denmark)}, volume = {20}, number = {8}, pages = {552-570}, pmid = {31177593}, issn = {1600-0854}, mesh = {Animals ; Endosomes/*metabolism ; Glucose/*metabolism ; *Homeostasis ; Humans ; *Lipid Metabolism ; Signal Transduction ; }, abstract = {The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type 2 diabetes, hypercholesterolemia and non-alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research.}, } @article {pmid31177561, year = {2019}, author = {Downes, MR and Xu, B and van der Kwast, TH}, title = {Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.}, journal = {Histopathology}, volume = {75}, number = {5}, pages = {715-722}, doi = {10.1111/his.13938}, pmid = {31177561}, issn = {1365-2559}, mesh = {Aged ; Aged, 80 and over ; Humans ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; *Neoplasm Grading ; Pelvic Neoplasms/*pathology/secondary ; Prognosis ; Prostate/pathology ; Prostatectomy ; Prostatic Neoplasms/*pathology ; Retrospective Studies ; }, abstract = {AIMS: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.

METHODS AND RESULTS: Lymph node-positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for the morphological patterns present. G was assigned to the metastasis based on percentage morphological patterns present. Statistical analysis used spss to assess disease-specific survival (DSS), disease-free survival (DFS) and distant metastasis-free survival (DMFS). One hundred and ten cases were identified: G5 (n = 52), G4 (n = 8), G3 (n = 34), G2 (n = 10) and no G (n = 6; treatment effect). IDC or CC was present in 103 (94%) specimens. More than one positive node correlated with worse DFS [P = 0.012, hazard ratio (HR) = 1.951, 95% confidence interval (CI) = 1.142-3.331] and DMFS (P = 0.009, HR = 2.647, 95% CI = 1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa = 0.073, P = 0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (P = 0.020, HR = 1.903, 95% CI = 1.091-3.320), DSS (P = 0.021, HR = 5.937, 95% CI = 1.084-32.533) and DMFS (P = 0.007, HR = 2.695, 95% CI = 1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS P = 0.033, HR = 0.431, 95% CI = 0.194-0.958).

CONCLUSIONS: IDC or CC is identified in 94% of node-positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma.}, } @article {pmid31174171, year = {2019}, author = {Stohl, S and Sprung, CL and Lippert, A and Pirracchio, R and Artigas, A and Iapichino, G and Harris, S and Pezzi, A and Schlesinger, M}, title = {Impact of triage-to-admission time on patient outcome in European intensive care units: A prospective, multi-national study.}, journal = {Journal of critical care}, volume = {53}, number = {}, pages = {11-17}, doi = {10.1016/j.jcrc.2019.05.013}, pmid = {31174171}, issn = {1557-8615}, mesh = {Aged ; Critical Care/standards/*statistics & numerical data ; Critical Illness/*mortality ; Cross-Sectional Studies ; Decision Making ; Europe ; Female ; Hospital Mortality ; Humans ; Intensive Care Units/*statistics & numerical data ; Male ; Middle Aged ; *Outcome Assessment, Health Care ; Patient Admission/statistics & numerical data ; Prospective Studies ; Simplified Acute Physiology Score ; Time Factors ; Triage/*statistics & numerical data ; }, abstract = {PURPOSE: Ubiquitous bed shortages lead to delays in intensive care unit (ICU) admissions worldwide. Assessing the impact of delayed admission must account for illness severity. This study examined both the relationship between triage-to-admission time and 28-day mortality and the impact of controlling for Simplified Acute Physiology Score (SAPS) II scores on that relationship.

METHODS: Prospective cross-sectional analysis of referrals to eleven ICUs in seven European countries between 2003 and 2005. Outcomes among patients admitted within versus after 4 h were compared using a Chi-square test. Triage-to-admission time was also analyzed as a continuous variable; outcomes were assessed using a non-parametric Kruskal-Wallis test.

RESULTS: Among 3175 patients analyzed, triage-to-admission time was 2.1 ± 3.9 h. Patients admitted within 4 h had higher SAPS II scores (33.6 versus 30.6, Pearson correlation coefficient -0.07, p < 0.0001). 28-day mortality was surprisingly higher among patients admitted earlier (29.6 vs 25.2%, OR 1.25, 95% CI 0.99-1.58, p = 0.06). Even after adjusting for SAPS II scores, delayed admission was not associated with higher mortality (OR 1.08, CI 0.83-1.41, p = 0.58).

CONCLUSIONS: Even after accounting for quantifiable parameters of illness severity, delayed admission did not negatively impact outcome. Triage practices likely influence outcomes. Severity scores may not fully reflect illness acuity or trajectory.}, } @article {pmid31172621, year = {2019}, author = {Hamzah, JL and Ong, KW and Tan, BY}, title = {Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {706-708}, doi = {10.1111/tbj.13308}, pmid = {31172621}, issn = {1524-4741}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/pathology ; Ultrasonography, Mammary ; }, abstract = {Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.}, } @article {pmid31171819, year = {2019}, author = {Chavez, DE and Gronau, I and Hains, T and Kliver, S and Koepfli, KP and Wayne, RK}, title = {Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8329}, pmid = {31171819}, issn = {2045-2322}, mesh = {*Adaptation, Physiological ; Animals ; Animals, Wild/genetics ; *Biological Evolution ; Body Patterning ; Canidae/*genetics ; Computational Biology ; DNA/analysis ; Diet ; Female ; *Genomics ; Genotype ; Hedgehog Proteins/genetics ; Molar ; Monte Carlo Method ; Pigmentation ; Predatory Behavior ; }, abstract = {Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.}, } @article {pmid31171772, year = {2019}, author = {Haythorne, E and Rohm, M and van de Bunt, M and Brereton, MF and Tarasov, AI and Blacker, TS and Sachse, G and Silva Dos Santos, M and Terron Exposito, R and Davis, S and Baba, O and Fischer, R and Duchen, MR and Rorsman, P and MacRae, JI and Ashcroft, FM}, title = {Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2474}, pmid = {31171772}, issn = {2041-1723}, support = {BB/L020874/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; MR/T002107/1/MRC_/Medical Research Council/United Kingdom ; 090532/Z/09/Z//Wellcome Trust (Wellcome)/International ; 884655//Wellcome Trust (Wellcome)/International ; FC001999/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001999/WT_/Wellcome Trust/United Kingdom ; 095531/WT_/Wellcome Trust/United Kingdom ; BB/P018726/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; FC001999/WT_/Wellcome Trust/United Kingdom ; 322620//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/International ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Diabetes Mellitus, Experimental/*genetics/metabolism ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Gene Expression Profiling ; Gluconeogenesis ; Glucose/*metabolism ; Glycolysis ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism ; Metabolomics ; Mice ; Mice, Transgenic ; Mitochondria/*metabolism ; NAD/metabolism ; Oxidative Phosphorylation ; Oxygen Consumption ; Potassium Channels, Inwardly Rectifying/genetics ; Proteomics ; }, abstract = {Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.}, } @article {pmid31171763, year = {2019}, author = {Kim, SJ and Kim, JY}, title = {An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {800-805}, pmid = {31171763}, issn = {1941-5923}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Mastectomy/*methods ; Neoplasm Recurrence, Local/*diagnostic imaging/surgery ; Rare Diseases ; Risk Assessment ; Skin Neoplasms/*secondary/surgery ; Ultrasonography, Doppler, Color/methods ; }, abstract = {BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.}, } @article {pmid31169985, year = {2019}, author = {Yamashita, H and Kurita, A and Azuma, S and Kudo, Y and Matsuzaki, N and Yazumi, S}, title = {Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.}, journal = {Diagnostic cytopathology}, volume = {47}, number = {10}, pages = {1037-1041}, doi = {10.1002/dc.24249}, pmid = {31169985}, issn = {1097-0339}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Diagnosis, Differential ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Middle Aged ; Mucin 5AC/genetics/*metabolism ; Pancreatic Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.}, } @article {pmid31164533, year = {2019}, author = {Suzuki, Y and Sakurai, K and Adachi, K and Kubota, H and Suzuki, S and Takei, S and Hara, Y and Enomoto, K and Hirano, T and Makishima, M}, title = {[Usefulness of Automated Breast Ultrasound for Deciding on a Surgical Approach in a Patient with Breast Cancer- A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {4}, pages = {778-780}, pmid = {31164533}, issn = {0385-0684}, mesh = {*Breast Neoplasms/diagnostic imaging/surgery ; Female ; Humans ; *Mastectomy ; Middle Aged ; Nipples ; Ultrasonography ; }, abstract = {Since breast reconstruction has been covered by health insurance, we can choose a procedure that combines the cosmetic satisfaction of patients with curability. We report about a patient with breast cancer that who underwent nipple-sparing mastectomy after evaluating the intraductal spread by automated breast ultrasound system(ABUS), while hand held ultrasound(HHUS)showed only limited information on the intraductal spread of the lesion. A 52-year old woman with an abnormal screening finding was referred to our hospital. HHUS showed an irregular and poorly defined hypoechoic mass lesion with a lactiferous duct extending to directly under the nipple. A core needle biopsy revealed invasive ductal carcinoma. We performed ABUS to assess the intraductal spread in the lesion because the patient requested breast reconstruction. The coronal section of the breast in the ABUS did not showintraductal spread. We, therefore, decided to perform a nipple-sparing mastectomy and sentinel lymph node biopsy. Intraoperative evaluation by frozen and permanent sections showed negative margins. The ABUS findings helped in the evaluation of the intraductal spread of the lesion and in the choice of the optimal procedure for the patient.}, } @article {pmid31164526, year = {2019}, author = {Yamamoto, K and Hayashi, K and Waraya, M and Habiro, T and Hosoya, S and Kosaka, Y and Sengoku, N and Hayakawa, K and Inukai, M and Watanabe, M}, title = {[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {4}, pages = {757-759}, pmid = {31164526}, issn = {0385-0684}, mesh = {*Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; }, abstract = {A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.}, } @article {pmid31163330, year = {2019}, author = {Khan, RN and Parvaiz, MA and Khan, AI and Loya, A}, title = {Invasive carcinoma in accessory axillary breast tissue: A case report.}, journal = {International journal of surgery case reports}, volume = {59}, number = {}, pages = {152-155}, pmid = {31163330}, issn = {2210-2612}, abstract = {INTRODUCTION: Accessory or ectopic breast tissue is an aberration of normal breast development. It is known to be a rare entity present anywhere along the embryologic mammary streak or milk line but more common in axilla.

PRESENTATION OF CASE: We report a case of 36 year old female with accessory breast carcinoma who presented with a progressive lump in her left axilla for 1 year. On examination a 2 cm solitary mass was palpable in axilla. Ultrasound confirmed a 19 mm mass with no other lesion in breast and axilla. Core biopsy showed invasive ductal carcinoma. She was discussed in multidisciplinary board meeting and was offered upfront surgery with excision of accessory breast tissue and sentinel lymph node biopsy. Axillary lymph node dissection was omitted following ACOSG Z0011 criteria. She was offered adjuvant chemotherapy and radiation post operatively along with endocrine treatment as she was hormone receptor positive.

DISCUSSION: Accessory breast development is hormone dependent just like normal breast. Breast cancer in accessory breast tissue is very rare. The incidence is around 6%. Most common pathology is invasive ductal carcinoma (50-75%). The most common location is axilla (60-70%) although it can present in other less common locations like infra-mammary region (5-10%) and rarely in thighs, perineum, groin, and vulva.

CONCLUSION: Since accessory axillary breast tissue is out of the image of screening breast examination, it is necessary for the oncologists to be aware of this entity and associated pathologies. Their preventive excision in high risk women can also be considered.}, } @article {pmid31153522, year = {2019}, author = {Zhu, B and Farouki, RT}, title = {A general framework for solving inverse dynamics problems in multi-axis motion control.}, journal = {ISA transactions}, volume = {95}, number = {}, pages = {130-143}, doi = {10.1016/j.isatra.2019.05.012}, pmid = {31153522}, issn = {1879-2022}, abstract = {An inverse dynamics compensation (IDC) scheme for the execution of curvilinear paths by multi-axis motion controllers is proposed. For a path specified by a parametric curve r(ξ), the IDC scheme computes a real-time path correction Δr(ξ) that (theoretically) eliminates path deviations incurred by the inertia and damping of the machine axes. To exploit the linear time-invariant nature of the dynamic equations, the correction term is computed as a function of elapsed time t, and the corresponding curve parameter values ξ are only determined as the final step of the IDC scheme, through a real-time interpolator algorithm. It is shown that, in general, the correction term for P, PI, and PID controllers consists of derivative, natural, and integral terms (the integrand of the latter involving only the path r(ξ), and not its derivatives). The use of lead segments to minimize transient effects associated with the initial conditions is also discussed, and the performance of the method is illustrated by simulation results. The IDC scheme is expressed in terms of a linear differential operator formalism to provide a clear, general, and systematic development, amenable to further adaptations and extensions.}, } @article {pmid31146042, year = {2019}, author = {Zhu, J and Sun, K and Xu, X and Sun, J and Kong, Q and Wang, S and Shi, J}, title = {A Preliminary Attempt of Nonintervention in the Treatment of Patients with Intervertebral Disc Calcification Combined with Ossification of the Posterior Longitudinal Ligament.}, journal = {World neurosurgery}, volume = {129}, number = {}, pages = {181-185}, doi = {10.1016/j.wneu.2019.05.169}, pmid = {31146042}, issn = {1878-8769}, mesh = {Child ; Female ; Humans ; Intervertebral Disc/*pathology ; Ossification of Posterior Longitudinal Ligament/*complications/pathology ; Ossification, Heterotopic/*complications/pathology ; Remission, Spontaneous ; *Watchful Waiting ; }, abstract = {BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, controversy remains in terms of the best way to treat this condition.

CASE DESCRIPTION: An 8-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurologic dysfunction. Computed tomography and magnetic resonance imaging revealed the calcified intervertebral disc and OPLL at the C5-C6 level and spinal cord compression. We performed a noninterventional strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and computed tomography revealed the complete resorption of ossified lesion. Magnetic resonance imaging also showed no sign of compression on the spinal cord and nerve root at the involved segment.

CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and sex-specific, further research is necessary. Treatment for IDC combined with OPLL needs to follow the treatment principles as described in the text.}, } @article {pmid31142340, year = {2019}, author = {Piasecka, D and Braun, M and Kitowska, K and Mieczkowski, K and Kordek, R and Sadej, R and Romanska, H}, title = {FGFs/FGFRs-dependent signalling in regulation of steroid hormone receptors - implications for therapy of luminal breast cancer.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {38}, number = {1}, pages = {230}, pmid = {31142340}, issn = {1756-9966}, support = {UMO-2017/27/B/NZ3/01474//Narodowym Centrum Nauki/ ; UMO-2015/17/B/NZ4/02157//Narodowe Centrum Nauki/ ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Cancer-Associated Fibroblasts/metabolism ; Female ; Fibroblast Growth Factors/*metabolism ; Humans ; Molecular Targeted Therapy ; Receptors, Estrogen/metabolism ; Receptors, Fibroblast Growth Factor/*metabolism ; Receptors, Progesterone/metabolism ; Receptors, Steroid/*metabolism ; *Signal Transduction ; Tumor Microenvironment ; }, abstract = {Stromal stimuli mediated by growth factor receptors, leading to ligand-independent activation of steroid hormone receptors, have long been implicated in development of breast cancer resistance to endocrine therapy. Mutations in fibroblast growth factor receptor (FGFR) genes have been associated with a higher incidence and progression of breast cancer. Increasing evidence suggests that FGFR-mediated interaction between luminal invasive ductal breast carcinoma (IDC) and its microenvironment contributes to the progression to hormone-independence. Therapeutic strategies based on FGFR inhibitors hold promise for overcoming resistance to the ER-targeting treatment. A series of excellent reviews discuss a potential role of FGFR in development of IDC. Here, we provide a concise updated summary of existing literature on FGFR-mediated signalling with an emphasis on an interaction between FGFR and estrogen/progesterone receptors (ER/PR) in IDC. Focusing on the regulatory role of tumour microenvironment in the activity of steroid hormone receptors, we compile the available functional data on FGFRs-mediated signalling, as a fundamental mechanism of luminal IDC progression and failure of anti-ER treatment. We also highlight the translational value of the presented findings and summarize ongoing oncologic clinical trials investigating FGFRs inhibition in interventional studies in breast cancer.}, } @article {pmid31142066, year = {2019}, author = {Zhao, JG and Nie, L and Chen, XQ and Chen, N and Zeng, H}, title = {[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {57}, number = {6}, pages = {422-427}, doi = {10.3760/cma.j.issn.0529-5815.2019.06.006}, pmid = {31142066}, issn = {0529-5815}, support = {81402110, 81672547//National Natural Science Foundation of China/ ; }, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/mortality/*pathology/secondary ; Retrospective Studies ; }, abstract = {Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.}, } @article {pmid31134761, year = {2019}, author = {Chen, S and Chen, H and Yi, Y and Jiang, X and Lei, H and Luo, X and Chen, Y and Liu, S and Yuan, D and Jia, X and Li, J}, title = {Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.}, journal = {Cancer medicine}, volume = {8}, number = {8}, pages = {4043-4054}, pmid = {31134761}, issn = {2045-7634}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology ; Population Surveillance ; Prognosis ; SEER Program ; }, abstract = {BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.

METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.

RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.

CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.}, } @article {pmid31130217, year = {2019}, author = {Yokoi, T and Morimoto, R and Oishi, H and Kato, H and Arao, Y and Yamaguchi, S and Kuwayama, T and Haga, T and Hiraiwa, H and Kondo, T and Furusawa, K and Fukaya, K and Sawamura, A and Okumura, T and Hirashiki, A and Murohara, T}, title = {Left Ventricular Relaxation Half-Time as a Predictor of Cardiac Events in Idiopathic Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy With Left Ventricular Systolic and/or Diastolic Dysfunction.}, journal = {The American journal of cardiology}, volume = {124}, number = {3}, pages = {435-441}, doi = {10.1016/j.amjcard.2019.05.005}, pmid = {31130217}, issn = {1879-1913}, mesh = {Cardiac Catheterization ; Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology ; Cardiomyopathy, Hypertrophic/diagnostic imaging/*physiopathology ; Diastole ; Echocardiography, Doppler ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Prognosis ; Systole ; Ventricular Dysfunction, Left/diagnostic imaging/*physiopathology ; }, abstract = {PURPOSE: Diastolic dysfunction preceding systolic dysfunction is considered an important interaction in cardiomyopathy with poor prognosis. The aim of this study was to compare left ventricular (LV) isovolumic relaxation with the other parameters as a potential prognostic marker for patients with idiopathic dilated cardiomyopathy (IDC) and hypertrophic cardiomyopathy (HC).

METHODS: A total of 145 patients with IDC and 116 with HC were evaluated for hemodynamic parameters; LV pressure was directly measured by a micromanometer catheter, and relaxation half-time (T1/2) was used to determine LV isovolumic relaxation. The median follow-up period was 4.7 years.

RESULTS: The mean ages of the patients with IDC and HC were 52.0 ± 12.0 and 57.1 ± 12.4 years, respectively. Each patient group was further divided into 2 groups based on the median value of T1/2: (1) <41.0 ms (D-L group) and ≥41.0 ms (D-H group) (2) <38.5 ms (H-L group) and ≥38.5 ms (H-H group). Kaplan-Meier analysis showed a significantly higher probability of cardiac events in the D-H group than in the D-L group (p = 0.001) and in the H-H group than in the H-L group (p = 0.028). Further, Cox proportional hazard regression analysis revealed that T1/2 was an independent predictor of cardiac events for patients with IDC (hazard ratio 1.109; p = 0.007) and HC (hazard ratio 1.062; p = 0.041). In conclusion, regardless of the type of cardiomyopathy, T1/2 as a measure of LV isovolumic relaxation function was found to be associated with the occurrence of cardiac events.}, } @article {pmid31129969, year = {2019}, author = {Li, JP and Zhang, XM and Zhang, YS and Zheng, LH and Liu, YJ}, title = {The prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in triple-negative breast cancer.}, journal = {Neoplasma}, volume = {66}, number = {5}, pages = {810-817}, doi = {10.4149/neo_2019_190107N26}, pmid = {31129969}, issn = {0028-2685}, mesh = {Carcinoma, Ductal, Breast/*diagnosis ; Disease-Free Survival ; Humans ; *Neoplasm Staging ; Prognosis ; Retrospective Studies ; Triple Negative Breast Neoplasms/*diagnosis ; United States ; }, abstract = {The American Joint Committee on Cancer (AJCC) released its 8th edition of cancer staging implemented in early 2018. This study aims to compare anatomic staging (AS) with prognostic staging (PS) based on the updated AJCC 8th edition staging manual. A retrospective single-center analysis of 313 triple-negative breast invasive ductal carcinoma patients who received surgery at department of breast surgery in the Fourth Hospital of Hebei Medical University from 01/2010 -12/2012 was performed. All cases were restaged using the AJCC 8th edition AS and PS system. The 7-year disease-free survival (DFS) and the 7-year overall survival (OS) rates were 76.30% and 78.27%, respectively. Applying the PS system, 277 (88.5%) patients of the AS groups were upstaged to the PS groups, 31 cases with IIIC and 5 cases with IV unchanged (11.5%) and no cases downstaged. Both 7-year DFS and 7-year OS were significantly different in the different AS and PS groups (all, p<0.001). The PS system was found to provide better prognostic information in patients with AS group IIB. A total of 43 patients with AS group IIB were upstaged by PS system, in which 30 patients were +2 upstaged to PS IIIB, and 13 patients were +3 upstaged to PS IIIC. PS IIIB and IIIC from AS IIB had significant differences in 7-year DFS (χ2=5.628, p=0.014) and 7-year OS (χ2=6.037, p=0.018). Both AS and PS systems proposed in the 8th edition of the AJCC breast cancer staging manual had prognostic value in TNBC. Moreover, the PS system predicts clinical outcomes of TNBC patients more accurately than the traditional AS system.}, } @article {pmid31124276, year = {2019}, author = {Tao, WJ and Zhang, HX and Zhang, LM and Gao, F and Huang, W and Liu, Y and Zhu, Y and Bai, GJ}, title = {Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.}, journal = {Journal of applied clinical medical physics}, volume = {20}, number = {7}, pages = {142-150}, pmid = {31124276}, issn = {1526-9914}, support = {BK20170626//Natural Science Foundation/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism ; Contrast Media/*pharmacokinetics ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Early Diagnosis ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Tissue Distribution ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS.

METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters K[trans] , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares.

RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of K[trans] , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of K[trans] , Kep , D and the combined indicator of K[trans] , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016).

CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.}, } @article {pmid31120568, year = {2019}, author = {Henry, NL and Cannon-Albright, LA}, title = {Breast cancer histologic subtypes show excess familial clustering.}, journal = {Cancer}, volume = {125}, number = {18}, pages = {3131-3138}, pmid = {31120568}, issn = {1097-0142}, support = {NU58DP0063200-01/CC/CDC HHS/United States ; HHSN261201800016I/CA/NCI NIH HHS/United States ; //University of Utah/ ; P30 CA42014//Huntsman Cancer Institute/ ; HHSN261201800016C/CA/NCI NIH HHS/United States ; //Utah Cancer Registry/ ; //Huntsman Cancer Foundation/ ; P30 CA042014/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/epidemiology/*genetics/pathology ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Lobular/epidemiology/*genetics/pathology ; Family ; Female ; Genetic Predisposition to Disease ; Humans ; Inflammatory Breast Neoplasms/epidemiology/*genetics/pathology ; Middle Aged ; Pedigree ; SEER Program ; Utah/epidemiology ; }, abstract = {BACKGROUND: The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype.

METHODS: By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives.

RESULTS: The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes.

CONCLUSIONS: These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.}, } @article {pmid31119054, year = {2019}, author = {Li, L and Wu, N and Li, F and Li, L and Wei, L and Liu, J}, title = {Clinicopathologic and molecular characteristics of 44 patients with pure secretory breast carcinoma.}, journal = {Cancer biology & medicine}, volume = {16}, number = {1}, pages = {139-146}, pmid = {31119054}, issn = {2095-3941}, abstract = {OBJECTIVE: Secretory breast carcinoma (SBC) is a rare type of breast malignancy, accounting for less than 0.02% of all infiltrating breast malignancies. The pure SBC, a type of SBC without another type of breast malignant neoplasm, is particularly rare. This study aimed to investigate the clinicopathologic and molecular features of pure SBC.

METHODS: The main pathological parameters such as estrogen receptor (ER), progesterone receptor (PR), and human epithelial growth factor receptor 2 (C-erbB-2) were detected by immunohistochemistry (IHC), and the clinicopathologic and prognostic difference were compared with invasive ductal carcinoma (IDC). Fluorescent in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the ETV6-NTRK3 rearrangement of SBC.

RESULTS: We found that the positivity rates of ER, PR, C-erbB-2, p53, and S-100 were 47.7% (21/44), 52.3% (23/44), 36.4% (16/44), 27.3% (12/44), and 95.5% (42/44), respectively, which were higher than those reported in previous studies. Special periodic acid-Schiff analysis was performed in 36 patients, and the value of the Ki-67 index ranged from 1% to 50% (mean value: 10%). Interestingly, most patients with pure SBC harbored an ETV6-NTRK3 rearrangement with an 88.6% (39/44) expression rate. Compared with IDC, the tumor size of most patients with SBC was larger than 2 cm (P = 0.024). Ultrasound showed benign lesions, and the total misdiagnosis rate was higher (P = 0.020). Although the pathological classification was mostly triple-negative breast cancers (P = 0.036), there was less metastasis (P = 0.029), and the overall prognosis was better than that of the IDC group.

CONCLUSIONS: Although axillary lymph node metastasis, local recurrence, or distant metastasis may occur, SBC is also considered an indolent neoplasm with a good prognosis. Once diagnosed, surgical treatment should be performed as soon as possible, followed by appropriate adjuvant chemotherapy, irradiation, and endocrine therapies.}, } @article {pmid31111698, year = {2019}, author = {Kosik, I and Brackstone, M and Kornecki, A and Chamson-Reig, A and Wong, P and Araghi, MH and Carson, JJ}, title = {Intraoperative photoacoustic screening of breast cancer: a new perspective on malignancy visualization and surgical guidance.}, journal = {Journal of biomedical optics}, volume = {24}, number = {5}, pages = {1-12}, pmid = {31111698}, issn = {1560-2281}, support = {220298//CIHR/Canada ; }, mesh = {Aged ; Aged, 80 and over ; Algorithms ; Breast Neoplasms/*diagnostic imaging/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery ; Diagnosis, Computer-Assisted/*methods ; Female ; Hemoglobins/analysis ; Humans ; Image Processing, Computer-Assisted ; Lipids/chemistry ; *Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Monitoring, Intraoperative ; Phantoms, Imaging ; Photoacoustic Techniques/methods ; Ultrasonography/methods ; }, abstract = {High re-excision rates in breast-conserving surgery call for a new intraoperative approach to the lumpectomy margin evaluation problem. The unique intraoperative imaging system, presented here, demonstrated the capability of photoacoustic tomography (PAT) to deliver optical sensitivity and specificity, along with over 2-cm imaging depth, in a clinical setting. The system enabled the evaluation of tumor extent, shape, morphology, and position within lumpectomy specimens measuring up to 11 cm in diameter. The investigation included all major breast cancer-related lesions, such as invasive ductal carcinoma (IDC), multifocal IDC, ductal carcinoma in situ and combinations of these variants. Coregistration with established ultrasound (US) technology, as well as comparison to specimen radiography, validated the performance of PAT, which appeared to facilitate better tumor visualization. Contrary to expected PA contrast mechanisms, PAT images of hemoglobin distribution correlated poorly with US-determined tumor location, while hypointense regions in lipid-weighted PAT images were in better agreement with US.}, } @article {pmid31111513, year = {2019}, author = {Shah, RB and Shore, KT and Yoon, J and Mendrinos, S and McKenney, JK and Tian, W}, title = {PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma).}, journal = {The Prostate}, volume = {79}, number = {11}, pages = {1267-1273}, doi = {10.1002/pros.23831}, pmid = {31111513}, issn = {1097-0045}, mesh = {Adenocarcinoma/*genetics/metabolism/pathology ; Alleles ; Biomarkers, Tumor ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Humans ; Male ; Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/*genetics/metabolism ; Prostatic Neoplasms/*genetics/metabolism/pathology ; }, abstract = {BACKGROUND: The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high-risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features.

METHODS: Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma.

RESULTS: Eight-eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC-P had the highest relative risk (4.993, 95% confidence interval, 3.451-7.223, P < 0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present.

CONCLUSIONS: PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC-P. This is the first study showing the association of PTEN loss with stromogenic PCa.}, } @article {pmid31109373, year = {2019}, author = {Tan, W and Tao, L and Zhou, Z and Yin, W and Chen, Y}, title = {Tumor-to-tumor metastasis: a rare case of breast carcinoma metastasizing to a pheochromocytoma, and a literature review.}, journal = {Diagnostic pathology}, volume = {14}, number = {1}, pages = {46}, pmid = {31109373}, issn = {1746-1596}, support = {NO. JCYJ201710//the Science and Research Foundation of Peking University, Shenzhen Hospital/ ; NO. SZSM201812088//the "San-ming" Project of Medicine in Shenzhen/ ; }, mesh = {Adrenal Gland Neoplasms/*diagnostic imaging/secondary ; Adrenal Glands/diagnostic imaging/pathology ; Adult ; Breast/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Pheochromocytoma/*diagnostic imaging/secondary ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Tumor-to-tumor metastasis is a well-recognized but uncommon entity. Breast carcinoma is one of the most common metastatic donors. Breast carcinoma metastasizes commonly to adrenal glands. However, the co-existence of a metastatic lesion with an existing adrenal tumor is a rare finding.

CASE PRESENTATION: A 35-year-old woman was diagnosed with pheochromocytoma using computed tomography and ultrasound examinations. The tumor was surgically removed. Histological and immunohistochemical staining suggested that there were two components in the tumor: pheochromocytoma and metastatic cancer.

CONCLUSION: This is the second published case of pheochromocytoma with tumor-to-tumor metastasis from an invasive ductal carcinoma of the breast. Furthermore, we highlight the importance of awareness of tumor-to-tumor metastasis in pathological diagnosis.}, } @article {pmid31107526, year = {2019}, author = {Nasir, A and Lehrke, HD and Mounajjed, T and Said, S and Zhang, L and Yasir, S and Shah, SS and Chandan, VS and Smyrk, TC and Moreira, RK and Boland Froemming, JM and Herrera Hernandez, LP and Wu, TT and Graham, RP}, title = {Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites.}, journal = {American journal of clinical pathology}, volume = {152}, number = {2}, pages = {190-199}, doi = {10.1093/ajcp/aqz032}, pmid = {31107526}, issn = {1943-7722}, mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Albumins/genetics/*metabolism ; Bile Duct Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; Cholangiocarcinoma/genetics/*metabolism/pathology ; Gallbladder Neoplasms/genetics/*metabolism/pathology ; Humans ; In Situ Hybridization ; Liver Neoplasms/genetics/*metabolism/pathology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized.

METHODS: Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays.

RESULTS: Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases.

CONCLUSIONS: Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.}, } @article {pmid31105119, year = {2019}, author = {Yokoyama, T and Makino, H and Hirakata, A and Ueda, J and Takata, H and Okusa, M and Kawashima, M and Tsujino, T and Hosone, M and Matsushita, A and Nakamura, Y and Yoshida, H}, title = {Conversion Surgery for Metastatic Pancreatic Mucinous Carcinoma Responsive to Systemic Chemotherapy with Modified FOLFIRINOX: A Case Report.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {86}, number = {5}, pages = {284-290}, doi = {10.1272/jnms.JNMS.2019_86-502}, pmid = {31105119}, issn = {1347-3409}, mesh = {Adenocarcinoma, Mucinous/diagnostic imaging/*drug therapy/pathology/*surgery ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Fluorouracil/therapeutic use ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Lymph Nodes/diagnostic imaging/pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Oxaliplatin/therapeutic use ; Pancreas/diagnostic imaging/pathology ; Pancreatic Neoplasms/diagnostic imaging/*drug therapy/pathology/*surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a case of metastatic pancreatic-head mucinous carcinoma (with multiple lymph node and bone metastases) and review the relevant literature. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for diagnosis, and a satisfactory outcome was achieved after systemic chemotherapy with FOLFIRINOX followed by resection of the primary lesion as conversion surgery. The patient was a 55-year-old man. Hematological findings included elevated serum tumor marker levels: CEA 12.7 ng/mL, DUPAN-2 400 U/mL. Findings from several imaging modalities and EUS-FNA confirmed a clinicopathological diagnosis of metastatic pancreatic mucinous carcinoma with multiple bone and lymph node metastases. Five courses of modified FOIFIRINOX (m-FFX) were given as systemic chemotherapy, which had an antitumor effect. Subtotal stomach-preserving pancreaticoduodenectomy and extensive lymph-node dissection were thus performed. Histopathological analysis showed invasive ductal carcinoma, muc (pT3, pN1b, cM1). After surgery, the clinical course was notable for the absence of complications. Tegafur/gimeracil/oteracil (S-1) was started as maintenance adjuvant chemotherapy postoperatively, and no disease progression has been observed at 10 months after surgery.}, } @article {pmid31104916, year = {2019}, author = {Kanat-Maymon, Y and Ben-David, BM}, title = {Small numbers are not predictive: Congenital blindness may or may not be protective for schizophrenia.}, journal = {Schizophrenia research}, volume = {209}, number = {}, pages = {274}, doi = {10.1016/j.schres.2019.04.023}, pmid = {31104916}, issn = {1573-2509}, mesh = {Blindness ; Humans ; *Schizophrenia ; Vision Disorders ; }, } @article {pmid31104457, year = {2019}, author = {Park, SY and Kim, HJ and Kim, WH and Cheon, HJ and Lee, H and Park, HY and Jung, JH and Park, JY}, title = {Feasibility of ultrasound-guided absorbable retaining thread needle localization for nonpalpable breast lesions.}, journal = {Ultrasonography (Seoul, Korea)}, volume = {38}, number = {3}, pages = {272-276}, pmid = {31104457}, issn = {2288-5919}, abstract = {PURPOSE: Absorbable retaining thread (ART) needle localization utilizes a guiding needle with a thread; this technique was invented to reduce patient discomfort and wire migration. We investigated the feasibility of ultrasound (US)-guided ART needle localization for nonpalpable breast lesions.

METHODS: ART needle localization was performed for 26 nonpalpable breast lesions in 26 patients who were scheduled to undergo surgical excision the day after localization. Seventeen breast lesions were initially diagnosed as invasive ductal carcinoma, six as ductal carcinomas in situ, and one as fibrocystic change. The other two cases without an initial pathologic diagnosis had suspicious US features, and excision was planned concomitantly with contralateral breast cancer surgery. The primary outcome was the technical success rate of ART needle localization confirmed by US immediately after the procedure, and the secondary outcomes were the percentage of clear margins on pathology and the complication rate of ART needle localization.

RESULTS: The technical success rate of ART needle localization was 96.2% (25 of 26 patients), and the ART was located 1 cm away from the mass in one patient (3.8%). The lesions were successfully removed with clear margins in all 26 patients. No significant complications related to ART needle localization were observed.

CONCLUSION: ART needle localization can be an alternative to wire needle localization for nonpalpable breast lesions.}, } @article {pmid31102571, year = {2019}, author = {Tonttila, PP and Ahtikoski, A and Kuisma, M and Pääkkö, E and Hirvikoski, P and Vaarala, MH}, title = {Multiparametric MRI prior to radical prostatectomy identifies intraductal and cribriform growth patterns in prostate cancer.}, journal = {BJU international}, volume = {124}, number = {6}, pages = {992-998}, doi = {10.1111/bju.14812}, pmid = {31102571}, issn = {1464-410X}, mesh = {Aged ; Humans ; Male ; Middle Aged ; *Multiparametric Magnetic Resonance Imaging ; *Prostate/diagnostic imaging/pathology/surgery ; Prostatectomy ; *Prostatic Neoplasms/diagnostic imaging/mortality/pathology/surgery ; Retrospective Studies ; }, abstract = {OBJECTIVES: To evaluate the diagnostic value of multiparametric prostate magnetic resonance imaging (mpMRI) prior to radical prostatectomy with curative intent for the detection of cribriform architecture (CA) and intraductal prostate cancer (IDC), which have recently been demonstrated to be adverse pathological features.

PATIENTS AND METHODS: The study included 124 men who underwent mpMRI prior to radical prostatectomy at our centre. Preoperative mpMRI, prostatectomy histology and clinical follow-up details were reviewed retrospectively. The diagnostic value of mpMRI was evaluated on the basis of the detection rate. Secondly, the prognostic significance of CA/IDC among grade group (GG)2 cancers with regard to biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier analysis, with the log rank test and Fisher's exact test.

RESULTS: Pathological examination of radical prostatectomy specimens identified CA/IDC in 89 of 124 cases (71%) and mpMRI identified 86/95 of tumours including any CA/IDC with a sensitivity of 90.5% (95% confidence interval 82.8-95.6%). When localization of the lesions was compared, there was an association between the highest Prostate Imaging-Reporting and Data System classification and the highest pathological grade in 106 of the 124 cases (85.5%). In patients with GG2 lesions, BCR occurred in 11 of 31 (35.5%) with CA/IDC and two of 21 (9.5%) without CA/IDC (P = 0.034).

CONCLUSION: Multiparametric MRI has good sensitivity for detection of pathological primary prostate cancer, including most cases with CA/IDC; however, reliable prediction of GG2 tumours with CA/IDC for individual risk stratification remains challenging.}, } @article {pmid31100224, year = {2018}, author = {Montironi, R and Zhou, M and Magi-Galluzzi, C and Epstein, JI}, title = {Features and Prognostic Significance of Intraductal Carcinoma of the Prostate.}, journal = {European urology oncology}, volume = {1}, number = {1}, pages = {21-28}, doi = {10.1016/j.euo.2018.03.013}, pmid = {31100224}, issn = {2588-9311}, mesh = {Biopsy ; Carcinoma, Ductal/*diagnosis/genetics ; Diagnosis, Differential ; Disease Management ; *Genomic Instability ; Humans ; Male ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/*diagnosis/genetics ; Tumor Burden ; }, abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is an intraglandular/ductal neoplastic growth of glandular epithelial cells characterized by marked abnormality of the glandular architecture and/or cytological atypia that exceeds what is typically seen in high-grade prostatic intraepithelial neoplasia (HPGIN). It has been shown that IDC-P is a strong independent indicator of poor prognosis for prostate carcinoma (PCa).

OBJECTIVE: To review the pathological and genetic features, diagnostic criteria and differential diagnosis, and clinical significance of IDC-P.

EVIDENCE ACQUISITION: PubMed was searched using keywords including prostate carcinoma, intraductal carcinoma, IDC, histology, diagnostic criteria, and prognosis. The references in relevant articles were also reviewed.

EVIDENCE SYNTHESIS: IDC-P is a distinct entity with characteristic morphological and genetic features. It is strongly associated with aggressive PCa with high Gleason score/grade groups and large tumor volume, and portends unfavorable clinical outcomes. Morphological diagnostic criteria have been established to distinguish it from other lesions with similar histological features. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant PCa. However, patients with isolated IDC-P in biopsy specimens are recommended to have either definitive treatment or immediate repeat biopsy.

CONCLUSIONS: It is critical to recognize and report IDC-P, especially in prostate biopsies, where the clinical impact of such a diagnosis is greatest.

PATIENT SUMMARY: Intraductal carcinoma is a unique form of aggressive prostate cancer. In this report, we review its pathological and genetic features and poor prognostic significance. It is critical for pathologists to recognize and report this lesion in prostate specimens, especially in prostate biopsies for patient management.}, } @article {pmid31092426, year = {2019}, author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Wojnar, A and Dziegiel, P}, title = {Correlation of Expression of CHI3L1 and Nogo-A and their Role in Angiogenesis in Invasive Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {39}, number = {5}, pages = {2341-2350}, doi = {10.21873/anticanres.13351}, pmid = {31092426}, issn = {1791-7530}, mesh = {Aged ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chitinase-3-Like Protein 1/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Neovascularization, Pathologic/*genetics ; Nogo Proteins/*genetics ; Receptors, Cell Surface/genetics ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor C/*genetics ; Vascular Endothelial Growth Factor D/genetics ; }, abstract = {BACKGROUND/AIM: Chitinase 3 like 1 (CHI3L1) is a secretion glycoprotein. Elevated levels of this protein are observed in cancer diseases. The biological role of CHI3L1 is not yet fully known, but the connection between CHI3L1 and angiogenesis has been shown. Recent reports also describe the association of Nogo isoforms and Nogo-B receptor (NgBR) with a proliferative potential, cancer cell invasiveness, and angiogenesis. The aim of this study was to evaluate the levels of CHI3L1, Nogo-A, Nogo-A/B, and NgBR and correlate them with clinical-pathological data, to study their role in angiogenesis in invasive ductal breast carcinoma (IDC).

MATERIALS AND METHODS: A total of 77 IDC cases were used in the study. Immunohistochemistry was used to determine the level of expression of CHI3L1, Nogo-A, Nogo-A/B, NgBR and vascular endothelial growth factors (VEGFA, VEGFC and VEGFD). The obtained results were subjected to statistical analysis including clinicalpathological data.

RESULTS: A statistically significant positive correlation of CHI3L1 and Nogo-A expression (r=0.474, p>0.0001) and a positive correlation of Nogo-A and VEGFC expression (r=0.280, p=0.013) were found.

CONCLUSION: CHI3L1 and Nogo-A are important in angiogenesis in IDC.}, } @article {pmid31090528, year = {2019}, author = {Shachar, T and Greenbaum, D}, title = {When a Push Becomes a Shove: Nudging in Elderly Care.}, journal = {The American journal of bioethics : AJOB}, volume = {19}, number = {5}, pages = {78-80}, doi = {10.1080/15265161.2019.1588415}, pmid = {31090528}, issn = {1536-0075}, mesh = {Aged ; Humans ; *Morals ; }, } @article {pmid31089799, year = {2019}, author = {Goh, CW and Wu, J and Ding, S and Lin, C and Chen, X and Huang, O and Chen, W and Li, Y and Shen, K and Zhu, L}, title = {Invasive ductal carcinoma with coexisting ductal carcinoma in situ (IDC/DCIS) versus pure invasive ductal carcinoma (IDC): a comparison of clinicopathological characteristics, molecular subtypes, and clinical outcomes.}, journal = {Journal of cancer research and clinical oncology}, volume = {145}, number = {7}, pages = {1877-1886}, pmid = {31089799}, issn = {1432-1335}, support = {81572581//National Natural Science Foundation of China/ ; 16411966900//Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission/ ; }, mesh = {Breast Neoplasms/*classification/metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*classification/metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*classification/metabolism/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes.

METHODS: Data from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated.

RESULTS: IDC/DCIS patients were more likely to be younger (P < 0.001), had low tumor grade (P = 0.001), had less lymph node involvement (P = 0.038) and received more mastectomy (P = 0.002) than IDC patients. In the comparison of molecular subtype prevalence, IDC/DCIS patients were more frequently presented with luminal B/HER2 positive (12.5% vs 11.0%, P < 0.001) and HER2 positive subtypes (20.9% vs 9.8%, P < 0.001). The 5-year disease-free survival (DFS, 90.9% vs 87.5%, P = 0.021) and 5-year overall survival (OS 96.1% vs 94.0%, P = 0.018) were significantly improved in IDC/DCIS patients compared to IDC patients. In multivariate analysis, the presence of coexisting DCIS (P = 0.048), tumor size (P < 0.001), lymph node status (P < 0.001), lymphovascular invasion (P = 0.007) and molecular subtypes (P < 0.001) were independent prognostic factors for DFS. Furthermore, coexistence of DCIS component in IDC significantly improved DFS in HER2 positive (94.8% vs 78.5%, P = 0.003), but had no association in luminal and triple negative subtypes.

CONCLUSIONS: IDC with coexisting DCIS was associated with improved prognosis. Patients with IDC/DCIS presented with more HER2 positive expression and might improve DFS in HER2 positive breast cancer.}, } @article {pmid31087408, year = {2019}, author = {Baydoun, S and Gonzalez, P and Whitman, GJ and Dryden, M and Xi, Y and Dogan, B}, title = {Is Ductography Still Warranted in the 21st century?.}, journal = {The breast journal}, volume = {25}, number = {4}, pages = {654-662}, doi = {10.1111/tbj.13302}, pmid = {31087408}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging/methods ; Mammography/*methods/statistics & numerical data ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVE: To determine the utility of ductography in conjunction with mammography and ultrasound in patients with pathologic nipple discharge, and the incremental role of MRI after triple-modality evaluation.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who had presented with pathologic nipple discharge and had undergone mammography and/or ultrasound and ductography between January 1, 2005, and October 31, 2010. We tested the diagnostic sensitivity, specificity and accuracy of combined triple-modality evaluation as well as of MRI performed in addition to these imaging techniques. We used the gold standard of image-guided biopsies, surgical excision, or long-term clinical and imaging follow-up.

RESULTS: Among 94 study patients, benign papillomas were identified in 42 (44.7%), abscess in one (1%), duct ectasia in four (4.3%), and malignancy (invasive ductal carcinoma or ductal carcinoma in situ) or high-risk lesion (atypical ductal hyperplasia) in 10 (10.6%). Forty-six patients (49%) underwent surgical excision; 89.1% of which had presurgical planning with ductography. In 35 (37.2%) with negative imaging, resolution of nipple discharge was confirmed on median clinical and imaging follow-up of 36 months. Two patients with negative imaging were lost to follow-up. Sensitivity, specificity, PPV, and NPV for accurately demonstrating the etiology of pathologic nipple discharge were 13%, 97%, 89%, and 37% respectively for mammography; 73%, 97%, 98%, and 64% respectively for ultrasound; 76%, 72%, 84%, and 61% respectively for ductography; 86%, 70%, 85%, and 72% respectively for combined ultrasound and ductography; and 75%, 100%, 100% and 67% respectively for DCE-MRI.

CONCLUSION: The combination of mammography, ultrasound and ductography is highly accurate for identifying the etiology of pathologic nipple discharge. DCE-MRI can be used as an alternate to ductography if necessary.}, } @article {pmid31073745, year = {2019}, author = {Schmöhl, F and Peters, V and Schmitt, CP and Poschet, G and Büttner, M and Li, X and Weigand, T and Poth, T and Volk, N and Morgenstern, J and Fleming, T and Nawroth, PP and Kroll, J}, title = {CNDP1 knockout in zebrafish alters the amino acid metabolism, restrains weight gain, but does not protect from diabetic complications.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {76}, number = {22}, pages = {4551-4568}, pmid = {31073745}, issn = {1420-9071}, support = {CRC 1118//Deutsche Forschungsgemeinschaft/ ; IRTG 1874/2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Amino Acids/*metabolism ; Animals ; Carnosine/metabolism ; Diabetes Complications/*metabolism ; Diabetes Mellitus, Type 2/metabolism ; Dipeptidases/*metabolism ; Gene Knockout Techniques/methods ; Kidney/metabolism ; Weight Gain/*physiology ; Zebrafish ; }, abstract = {The gene CNDP1 was associated with the development of diabetic nephropathy. Its enzyme carnosinase 1 (CN1) primarily hydrolyzes the histidine-containing dipeptide carnosine but other organ and metabolic functions are mainly unknown. In our study we generated CNDP1 knockout zebrafish, which showed strongly decreased CN1 activity and increased intracellular carnosine levels. Vasculature and kidneys of CNDP1[-/-] zebrafish were not affected, except for a transient glomerular alteration. Amino acid profiling showed a decrease of certain amino acids in CNDP1[-/-] zebrafish, suggesting a specific function for CN1 in the amino acid metabolisms. Indeed, we identified a CN1 activity for Ala-His and Ser-His. Under diabetic conditions increased carnosine levels in CNDP1[-/-] embryos could not protect from respective organ alterations. Although, weight gain through overfeeding was restrained by CNDP1 loss. Together, zebrafish exhibits CN1 functions, while CNDP1 knockout alters the amino acid metabolism, attenuates weight gain but cannot protect organs from diabetic complications.}, } @article {pmid31068293, year = {2019}, author = {Zhao, Z and Liu, Q and Wu, C and Guo, W and Li, J}, title = {[Expression of G9a in breast cancer and its effect on proliferation of breast cancer cells in vitro].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {39}, number = {4}, pages = {477-484}, pmid = {31068293}, issn = {1673-4254}, mesh = {*Breast Neoplasms ; Cell Proliferation ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Prognosis ; }, abstract = {OBJECTIVE: To study the expression of G9a in human breast cancer, its association with the clinicopathological characteristics of breast cancer, and its effect on the proliferation of breast cancer cells.

METHODS: A total of 122 specimens of breast cancer tissues and 61 adjacent normal tissues resected between October, 2016 and October, 2017 were obtained from the Tissue Bank of Ningxia Medical University General Hospital. Immunohistochemistry and real-time PCR were used to detect the expression of G9a in the breast cancer tissues. The relationship of G9a with the clinicopathological features of the patients, molecular subtypes of breast cancer and the immunohistochemical markers was analyzed. A bioinformatics approach was used to analyze the expression of G9a in breast tissues and its association with the prognosis of the patients with breast cancer. UNC0631, a G9a inhibitor, was used to investigate the effect of G9a on the proliferation of breast cancer cells in vitro.

RESULTS: The results of immunohistochemical study, real-time PCR and bioinformatics analysis showed that G9a was highly expressed in human breast cancer tissues. G9a was highly expressed in breast invasive ductal carcinoma, and its expression was negatively correlated with age (P < 0.05). Her-2-overexpressing breast cancer showed high expressions of G9a, which was positively correlated with the expressions of Her-2, Ki-67 and E-cadherin (P < 0.05). Bioinformatics analysis suggested that a high G9a expression was an independent risk factor for poor prognosis of breast cancer. In cultured breast cancer cells, the application of the G9a inhibitor significantly inhibited the cell proliferation.

CONCLUSIONS: G9a is highly expressed in breast cancer tissues to promote the development and progression of breast cancer. A high G9a expression is an independent risk factor for poor prognosis of breast cancer, and G9a may serve as a new target for early diagnosis and treatment of breast cancer.}, } @article {pmid31068072, year = {2020}, author = {Saguy, T and Fernández, S and Branscombe, NR and Shany, A}, title = {Justice Agents: Discriminated Group Members Are Perceived to be Highly Committed to Social Justice.}, journal = {Personality & social psychology bulletin}, volume = {46}, number = {1}, pages = {155-167}, doi = {10.1177/0146167219845922}, pmid = {31068072}, issn = {1552-7433}, mesh = {Adult ; Female ; Humans ; Male ; Minority Groups/*psychology ; Social Discrimination/*psychology ; Social Justice/*psychology ; Social Marginalization/psychology ; Social Perception/*psychology ; }, abstract = {We propose that because members of discriminated (vs. advantaged) groups have a history of dealing with injustice, majority group members expect them to be more committed to social justice. By commitment to social justice, we mean supporting, and caring for, the basic rights of virtually any marginalized group. Studies 1a (N = 145) and 1b (N = 120) revealed that members of discriminated (vs. relatively advantaged) groups were seen as having a stronger commitment to social justice. This was explained by participants' perception of discriminated groups as having a tradition of fighting injustice (Study 2; N = 174). Demonstrating implications of these perceptions, discriminated (relative to advantaged) group members were assigned more justice-related roles in the workplace (Study 3a: N = 120; Study 3b: N = 126; Study 4: N = 133), and their justice-related initiatives were rated more negatively (Study 5: N = 259). Theoretical and practical implications regarding minority-majority relations and minorities' ability to advance in workplace hierarchies are discussed.}, } @article {pmid31065446, year = {2018}, author = {Wang, J and Xu, Y and Mesa, KJ and South, FA and Chaney, EJ and Spillman, DR and Barkalifa, R and Marjanovic, M and Carney, PS and Higham, AM and Liu, ZG and Boppart, SA}, title = {Complementary use of polarization-sensitive and standard OCT metrics for enhanced intraoperative differentiation of breast cancer.}, journal = {Biomedical optics express}, volume = {9}, number = {12}, pages = {6519-6528}, pmid = {31065446}, issn = {2156-7085}, support = {R01 CA213149/CA/NCI NIH HHS/United States ; R01 EB023232/EB/NIBIB NIH HHS/United States ; }, abstract = {We report the development and implementation of an intraoperative polarization-sensitive optical coherence tomography (PS-OCT) system for enhancing breast cancer detection. A total of 3440 PS-OCT images were intraoperatively acquired from 9 human breast specimens diagnosed by H&E histology as healthy fibro-adipose tissue (n = 2), healthy stroma (n = 2), or invasive ductal carcinoma (IDC, n = 5). A standard OCT-based metric (coefficient of variation (CV)) and PS-OCT-based metrics sensitive to biological tissue from birefringence (i.e., retardation and degree of polarization uniformity (DOPU)) were derived from 398 statistically different and independent images selected by correlation coefficient analysis. We found the standard OCT-based metric and PS-OCT-based metrics were complementary for the differentiation of healthy fibro-adipose tissue, healthy stroma, and IDC. While the CV of fibro-adipose tissue was significantly higher (p<0.001) than those of either stroma or IDC, the CV difference between stroma and IDC was minimal. On the other hand, stroma was associated with significantly higher (p<0.001) retardation and significantly lower (p<0.001) DOPU as compared to IDC. By leveraging the complementary information acquired by the intraoperative PS-OCT system, healthy fibro-adipose tissue, healthy stroma, and IDC can be differentiated with an accuracy of 89.4%, demonstrating the potential of PS-OCT as an adjunct modality for enhanced intraoperative differentiation of human breast cancer.}, } @article {pmid31065432, year = {2018}, author = {Allen, WM and Foo, KY and Zilkens, R and Kennedy, KM and Fang, Q and Chin, L and Dessauvagie, BF and Latham, B and Saunders, CM and Kennedy, BF}, title = {Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.}, journal = {Biomedical optics express}, volume = {9}, number = {12}, pages = {6331-6349}, pmid = {31065432}, issn = {2156-7085}, abstract = {It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery. As a result, it remains unclear if the mechanical contrast observed is maintained in WLE specimens. In this manuscript, we begin to address this issue by performing a feasibility study of OCME on 17 freshly excised, intact WLE specimens. In addition, we present two developments required to sustain the progression of OCME towards intraoperative deployment. First, to enable the rapid visualization of en face images required for intraoperative assessment, we describe an automated segmentation algorithm to fuse en face micro-elastograms with OCT images to provide dual contrast images. Secondly, to validate contrast in micro-elastograms, we present a method that enables co-registration of en face images with histology of WLE specimens, sectioned in the orthogonal plane, without any modification to the standard clinical workflow. We present a summary of the observations across the 17 specimens imaged in addition to representative micro-elastograms and OCT images demonstrating contrast in a number of tumor margins, including those involved by invasive ductal carcinoma, mucinous carcinoma, and solid-papillary carcinoma. The results presented here demonstrate the potential of OCME for imaging tumor margins.}, } @article {pmid31063527, year = {2019}, author = {Ciurea, AI and Boca, I and Rogojan, L and Ciule, LD and Ciortea, CA}, title = {Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.}, journal = {Medical ultrasonography}, volume = {21}, number = {2}, pages = {200-203}, doi = {10.11152/mu-1769}, pmid = {31063527}, issn = {2066-8643}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Fatal Outcome ; Female ; Humans ; Muscle Neoplasms/*diagnostic imaging/*secondary ; Neoplasm Recurrence, Local/*diagnostic imaging ; Pectoralis Muscles/*diagnostic imaging ; Ultrasonography, Mammary/*methods ; }, abstract = {Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.}, } @article {pmid31062495, year = {2019}, author = {Ichihara, S and Moritani, S and Nishimura, R and Oiwa, M and Morita, T and Hayashi, T and Kato, A and Endo, T and Kada, A and Ito, N and Kuroishi, T and Sato, Y}, title = {Polygon method: A systematic margin assessment for breast conservation.}, journal = {Cancer medicine}, volume = {8}, number = {7}, pages = {3359-3369}, pmid = {31062495}, issn = {2045-7634}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/*surgery ; Female ; Humans ; Male ; *Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {BACKGROUND: Radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS) may be overtreatment for some, especially for those in which DCIS is eradicated, and ipsilateral breast tumor recurrence (IBTR) risk approaches the contralateral breast cancer (CBC) level. The aim of this study was to clarify whether the polygon method, a new systematic method of en face (tangential, shaved) margin assessment, can identify a subset of DCIS that can be safely treated by BCS alone.

METHODS: A key tool of the polygon method is an adjustable mold that prevents the "pancake phenomenon" (flattening) of breast tissue after surgical removal so that the specimen is fixed in the shape of a polygonal prism. This preanalytical procedure enables us to command a panoramic view of entire en face margins 3-5-mm deep from the real peripheral cut surfaces. Competing risk analysis was used to quantify rates of IBTR and CBC and to evaluate risk factors.

RESULTS: From 2000 to 2013, we identified 146 DCIS patients undergoing BCS with a contralateral breast at risk. In 100 DCIS patients whose margin was negative by the polygon method, 5 IBTR (3 DCIS and 2 invasive ductal carcinoma [IDC]) and 10 CBC (6 DCIS and 4 IDC) cases were identified during a median follow-up of 7.6 years (range, 0.9-17.4). Five- and 10-year cumulative incidence rates were 3.0% and 5.3% for IBTR, and 7.1% and 13.3% for CBC, respectively. Thus, patients with a negative margin consistently showed at least twofold lower IBTR than CBC despite omission of RT.

CONCLUSIONS: Japanese women classified with a negative margin by the polygon method show a very low risk of IBTR and account for approximately half of CBC cases. In this subset of DCIS patients, additional RT is not beneficial.}, } @article {pmid31060593, year = {2019}, author = {Petridis, C and Arora, I and Shah, V and Megalios, A and Moss, C and Mera, A and Clifford, A and Gillett, C and Pinder, SE and Tomlinson, I and Roylance, R and Simpson, MA and Sawyer, EJ}, title = {Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years.}, journal = {Breast cancer research : BCR}, volume = {21}, number = {1}, pages = {58}, pmid = {31060593}, issn = {1465-542X}, support = {MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; 8873/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Age Factors ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/epidemiology/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/*genetics ; Case-Control Studies ; Checkpoint Kinase 2/genetics ; Computational Biology ; DNA Copy Number Variations ; Female ; *Gene Frequency ; Genotype ; *Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Neoplasm Grading ; Tumor Suppressor Protein p53/genetics ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal breast cancer, and approximately 20% of screen-detected tumours are pure DCIS. Most risk factors for breast cancer have similar associations with DCIS and IDC; however, there is limited data on the prevalence of the known high and moderate penetrance breast cancer predisposition genes in DCIS and which women with DCIS should be referred for genetic screening. The aim of this study was to assess the frequency of germline variants in BRCA2, BRCA1, CHEK2, PALB2 and TP53 in DCIS in women aged less than 50 years of age.

METHODS: After DNA extraction from the peripheral blood, Access Array technology (Fluidigm) was used to amplify all exons of these five known breast cancer predisposition genes using a custom made targeted sequencing panel in 655 cases of pure DCIS presenting in women under the age of 50 years together with 1611 controls.

RESULTS: Case-control analysis revealed an excess of pathogenic variants in BRCA2 (OR = 27.96, 95%CI 6.56-119.26, P = 2.0 × 10[-10]) and CHEK2 (OR = 8.04, 95%CI 2.93-22.05, P = 9.0 × 10[-6]), with weaker associations with PALB2 (P = 0.003), BRCA1 (P = 0.007) and TP53 (P = 0.02). For oestrogen receptor (ER)-positive DCIS the frequency of pathogenic variants was 9% under the age of 50 (14% with a family history of breast cancer) and 29% under the age of 40 (42% with a family history of breast cancer). For ER-negative DCIS, the frequency was 9% (16% with a family history of breast cancer) and 8% (11% with a family history of breast cancer) under the ages of 50 and 40, respectively.

CONCLUSIONS: This study has shown that breast tumourigenesis in women with pathogenic variants in BRCA2, CHEK2, PALB2, BRCA1 and TP53 can involve a DCIS precursor stage and that the focus of genetic testing in DCIS should be on women under the age of 40 with ER-positive DCIS.}, } @article {pmid31057361, year = {2019}, author = {Aplin, FP and Fridman, GY}, title = {Implantable Direct Current Neural Modulation: Theory, Feasibility, and Efficacy.}, journal = {Frontiers in neuroscience}, volume = {13}, number = {}, pages = {379}, pmid = {31057361}, issn = {1662-4548}, support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.}, } @article {pmid31054033, year = {2019}, author = {Cohen, EN and Fouad, TM and Lee, BN and Arun, BK and Liu, D and Tin, S and Gutierrez Barrera, AM and Miura, T and Kiyokawa, I and Yamashita, J and Alvarez, RH and Valero, V and Woodward, WA and Shen, Y and Ueno, NT and Cristofanilli, M and Reuben, JM}, title = {Elevated serum levels of sialyl Lewis X (sLe[X]) and inflammatory mediators in patients with breast cancer.}, journal = {Breast cancer research and treatment}, volume = {176}, number = {3}, pages = {545-556}, pmid = {31054033}, issn = {1573-7217}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA138239/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms/*blood/*diagnosis/mortality ; Case-Control Studies ; Cluster Analysis ; Cytokines/blood ; Female ; Humans ; Inflammation Mediators/*blood ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Sialyl Lewis X Antigen/*blood ; Survival Analysis ; }, abstract = {PURPOSE: The carbohydrate sialyl Lewis[X] (sLe[X]) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLe[X] and inflammatory cytokines/chemokines in breast cancer sera.

METHODS: We retrospectively measured sLe[X] and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLe[X] and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLe[X] using a cut-off of 8 U/mL as previously defined.

RESULTS: Median serum sLe[X] was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLe[X] > 8 U/mL have a significantly shorter progression-free survival (PFS) (P = 0.0074) and overall survival (OS (P = 0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P = 0.001 and P < 0.001, respectively) and PFS (P = 0.010 and P < 0.001, respectively). sLe[X], MCP-1 and IP-10 remained significant in multivariate survival analysis.

CONCLUSION: Elevated serum sLe[X] was associated with invasive cancer but not DCIS. High serum sLe[X] levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLe[X] may have prognostic value in breast cancer.}, } @article {pmid31049740, year = {2019}, author = {Sanderink, WBG and Laarhuis, BI and Strobbe, LJA and Sechopoulos, I and Bult, P and Karssemeijer, N and Mann, RM}, title = {A systematic review on the use of the breast lesion excision system in breast disease.}, journal = {Insights into imaging}, volume = {10}, number = {1}, pages = {49}, pmid = {31049740}, issn = {1869-4101}, abstract = {PURPOSE: To outline the current status of and provide insight into possible future research on the breast lesion excision system (BLES) as a diagnostic and therapeutic device.

METHODS: A systematic search of the literature was performed using PubMed, Embase, and the Cochrane databases to identify relevant studies published between January 2002 and April 2018. Studies were considered eligible for inclusion if they evaluated the diagnostic or therapeutic accuracy or safety of BLES.

RESULTS: Ultimately, 17 articles were included. The reported underestimation rates of atypical ductal hyperplasia and ductal carcinoma in situ (DCIS) ranged from 0 to 14.3% and from 0 to 22.2%, respectively. Complete excision rates for invasive ductal carcinoma and DCIS ranged from 5.3 to 76.3%. Bleeding was the most frequently reported complication (0-11.8%). Device-related complications may arise, with an empty basket being the most common (0.6-3.6%). Thermal damage of the specimen, caused by the use of a radiofrequency cutting wire, was reported in eight of the included studies. Most thermal artifacts were reported as superficial and small (0.1-1.9 mm).

CONCLUSIONS: The BLES, an automated, image-guided, single-pass biopsy system for breast lesions using radiofrequency is designed to excise and retrieve an intact tissue specimen. It is an efficient and safe breast biopsy method with acceptable complication rates, which may be used as an alternative to vacuum-assisted biopsies. The variable rate of complete excision raises questions about the possibility to use BLES as a therapeutic device for the excision of small lesions. Further research should focus on this aspect of BLES.}, } @article {pmid31046734, year = {2019}, author = {Aras, S and Maroun, MC and Song, Y and Bandyopadhyay, S and Stark, A and Yang, ZQ and Long, MP and Grossman, LI and Fernández-Madrid, F}, title = {Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {411}, pmid = {31046734}, issn = {1471-2407}, support = {R01 CA122277/CA/NCI NIH HHS/United States ; R01 CA122277//National Institutes of Health/ ; W81XWH-16-1-0516//U.S. Department of Defense/ ; }, mesh = {Autoantigens/metabolism ; Autoimmunity ; Breast Neoplasms/*diagnosis/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Neoplasm Invasiveness ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Prospective Studies ; Protein Array Analysis ; Rapamycin-Insensitive Companion of mTOR Protein/genetics ; Transcription Factors/*genetics/*metabolism ; Up-Regulation ; }, abstract = {BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.

METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.

RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.

CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.}, } @article {pmid31045815, year = {2019}, author = {Li, JP and Zhang, XM and Zhang, Z and Zheng, LH and Jindal, S and Liu, YJ}, title = {Association of p53 expression with poor prognosis in patients with triple-negative breast invasive ductal carcinoma.}, journal = {Medicine}, volume = {98}, number = {18}, pages = {e15449}, pmid = {31045815}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Ductal/*mortality/*pathology ; Disease-Free Survival ; Female ; Genes, p53/*physiology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Triple Negative Breast Neoplasms/*mortality/*pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.}, } @article {pmid31040709, year = {2019}, author = {Hinnen, D and Kruger, DF}, title = {Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {12}, number = {}, pages = {447-455}, pmid = {31040709}, issn = {1178-7007}, abstract = {BACKGROUND: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases.

PURPOSE: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D.

CONCLUSION: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions.}, } @article {pmid31032548, year = {2019}, author = {Caterson, ID and Alfadda, AA and Auerbach, P and Coutinho, W and Cuevas, A and Dicker, D and Hughes, C and Iwabu, M and Kang, JH and Nawar, R and Reynoso, R and Rhee, N and Rigas, G and Salvador, J and Sbraccia, P and Vázquez-Velázquez, V and Halford, JCG}, title = {Gaps to bridge: Misalignment between perception, reality and actions in obesity.}, journal = {Diabetes, obesity & metabolism}, volume = {21}, number = {8}, pages = {1914-1924}, pmid = {31032548}, issn = {1463-1326}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Attitude of Health Personnel ; *Attitude to Health ; Chronic Disease ; Cross-Sectional Studies ; Female ; Health Personnel/*psychology ; Humans ; Male ; Middle Aged ; Motivation ; Obesity/*psychology ; Perception ; Surveys and Questionnaires ; Young Adult ; }, abstract = {AIMS: Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs).

MATERIALS AND METHODS: An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care.

RESULTS: A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required.

CONCLUSIONS: Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.}, } @article {pmid31032134, year = {2019}, author = {Trihia, HJ and Novkovic, N and Provatas, I and Mavrogiorgis, A and Lianos, E}, title = {Primary Alveolar Rhabdomyosarcoma of the Breast in an Adult: An Extremely Rare Case.}, journal = {Case reports in pathology}, volume = {2019}, number = {}, pages = {6098747}, pmid = {31032134}, issn = {2090-6781}, abstract = {Sarcomas of the breast constitute less than 1% of all malignant breast tumors and primary rhabdomyosarcoma (RMS) is a very rare entity with limited case reports in the literature. RMS is common in children and adolescents and rare in adults. Primary RMS arising from the breast is exceedingly rare in adults. We report a case of a primary RMS of the breast in a 60-year-old woman, who presented in an early stage, mimicking invasive ductal carcinoma clinically and is in complete remission after three years of diagnosis and one year of treatment.}, } @article {pmid31026796, year = {2019}, author = {Yao, Y and Sun, L and Meng, Y and Zhuang, Y and Zhao, L and Yu, Q and Si, C}, title = {Breast-Conserving Surgery in Patients With Mammary Paget's Disease.}, journal = {The Journal of surgical research}, volume = {241}, number = {}, pages = {178-187}, doi = {10.1016/j.jss.2019.03.025}, pmid = {31026796}, issn = {1095-8673}, mesh = {Breast/pathology/surgery ; Breast Neoplasms/mortality/pathology/*therapy ; Breast Neoplasms, Male/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision/statistics & numerical data ; Male ; Mastectomy, Radical/methods/*statistics & numerical data/trends ; Mastectomy, Segmental/methods/*statistics & numerical data/trends ; Paget's Disease, Mammary/mortality/pathology/*therapy ; Patient Selection ; Radiotherapy, Adjuvant/statistics & numerical data ; Retrospective Studies ; SEER Program/statistics & numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: We aimed to analyze the association between Paget's disease (PD) and breast cancer (BC) subtypes and compare the effect of breast-conserving surgery (BCS) as a local treatment with mastectomy for PD.

MATERIALS AND METHODS: Data of patients with histologic type International Classification of Diseases-0-3 8540-8543 who were treated from 1973 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. A chi-square test was used to identify differences in categorical data among different groups. Overall survival (OS) was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, sequential landmark analysis, and propensity score-matched analysis.

RESULTS: The study cohort included 5398 patients. Triple-negative BC accounted for the fewest patients with PD-only (1/22, 4.54%), Paget's disease-ductal carcinoma in situ (PD-DCIS) (3/48, 6.25%), and Paget's disease-invading ductal carcinoma (PD-IDC) (23/352, 6.53%). According to the results of the log-rank test and Cox analysis, the 10-year OS rates were similar for the BCS and mastectomy subgroups among patients with PD-DCIS or PD-IDC. Furthermore, there were no significant differences in survival benefits among the different surgeries after propensity score matching. Landmark analyses for OS of patients with PD-DCIS or PD-IDC surviving more than 1, 3, and 5 y showed no significant differences in survival. There were statistical differences in 10-year OS rates for patients with PD-DCIS or PD-IDC who underwent radiation therapy, or not, following BCS (both, P < 0.001).

CONCLUSIONS: For patients with PD-DCIS or PD-IDC, breast conservation therapy with lumpectomy and radiation is an effective local treatment strategy, compared with mastectomy.}, } @article {pmid31026792, year = {2019}, author = {Marull, J and Herrando, S and Brotons, L and Melero, Y and Pino, J and Cattaneo, C and Pons, M and Llobet, J and Tello, E}, title = {Building on Margalef: Testing the links between landscape structure, energy and information flows driven by farming and biodiversity.}, journal = {The Science of the total environment}, volume = {674}, number = {}, pages = {603-614}, doi = {10.1016/j.scitotenv.2019.04.129}, pmid = {31026792}, issn = {1879-1026}, mesh = {Agriculture ; Animals ; Biodiversity ; Birds ; Butterflies ; Conservation of Natural Resources/*methods ; Ecosystem ; *Environmental Monitoring ; Farms ; Humans ; }, abstract = {The aim of this paper is to test two methodologies, applicable to different spatial scales (from regional to local), to predict the capacity of agroecosystems to provide habitats for the species richness of butterflies and birds, based on the ways their socio-metabolic flows change the ecological functionality of bio-cultural landscapes. First, we use the more general Intermediate Disturbance-Complexity (IDC) model to assess how different levels of human appropriation of photosynthetic production affect the landscape functional structure that hosts biodiversity. Second, we apply a more detailed Energy-Landscape Integrated Analysis (ELIA) model that focusses on the energy storage carried out by the internal biomass loops, and the energy information held in the network of energy flows driven by farmers, in order to correlate both (the energy reinvested and redistributed) with the energy imprinted in the landscape patterns and processes that sustain biodiversity. The results obtained after applying both models in the province and the metropolitan region of Barcelona support the Margalef's energy-information-structure hypothesis by showing positive relations between butterflies' species richness, IDC and ELIA, and between birds' species richness and energy information. Our findings support the view that strong relationships between farming energy flows, agroecosystem functioning and biodiversity can be detected, and highlight the importance of farmers' knowledge and labour to maintain bio-cultural landscapes.}, } @article {pmid31025722, year = {2019}, author = {Kato, M and Hirakawa, A and Kobayashi, Y and Yamamoto, A and Ishida, R and Sano, T and Kimura, T and Majima, T and Ishida, S and Funahashi, Y and Sassa, N and Fujita, T and Matsukawa, Y and Yamamoto, T and Hattori, R and Gotoh, M and Tsuzuki, T}, title = {The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.}, journal = {The Prostate}, volume = {79}, number = {10}, pages = {1065-1070}, doi = {10.1002/pros.23818}, pmid = {31025722}, issn = {1097-0045}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/blood/*pathology/surgery ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/*pathology/surgery ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P.

METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy.

RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively).

CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.}, } @article {pmid31023035, year = {2019}, author = {Albayrak, M and Senol, O and Demirkaya-Miloglu, F and Calik, M and Kadioglu, Y}, title = {Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.}, journal = {Bratislavske lekarske listy}, volume = {120}, number = {3}, pages = {184-187}, doi = {10.4149/BLL_2019_031}, pmid = {31023035}, issn = {0006-9248}, mesh = {Adult ; *Breast Neoplasms/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; Female ; Humans ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; }, abstract = {OBJECTIVES: Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples.

METHODS: Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model.

RESULTS: Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones.

CONCLUSION: This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).}, } @article {pmid31022251, year = {2019}, author = {Ishikane, M and Hayakawa, K and Kutsuna, S and Takeshita, N and Ohmagari, N}, title = {The impact of infectious disease consultation in candidemia in a tertiary care hospital in Japan over 12 years.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0215996}, pmid = {31022251}, issn = {1932-6203}, mesh = {Aged ; Candidemia/*epidemiology/mortality ; Communicable Diseases/*epidemiology ; Female ; Humans ; Japan/epidemiology ; Kaplan-Meier Estimate ; Male ; *Referral and Consultation ; *Tertiary Care Centers ; }, abstract = {BACKGROUND: Candidemia is one of the major causes of morbidity and mortality as a hospital acquired infection. Infectious diseases consultation (IDC) might be beneficial to improve candidemia outcomes; however, only limited data from short periods of time are available thus far.

METHODS: An observational study of all candidemia patients at a large tertiary care hospital between 2002 and 2013 was conducted. A candidemia episode was defined as ≥ 1 positive result for Candida spp. in blood culture. Patients who died or transferred to another hospital within two days after their first positive blood culture were excluded. Independent risk factors for 30-day mortality were determined.

RESULTS: Among 275 patients with 283 episodes of candidemia, 194 (68.6%) were male, and the mean age was 70.0 ± 15.8 years. Central line-associated bloodstream infections, peripheral line-associated bloodstream infections, intra-abdominal infection, and unknown source comprised 220 (77.7%), 35 (12.4%), 13 (4.7%), and 15 (5.3%) episodes, respectively. A total of 126 patients (44.5%) received IDC. Factors independently associated with 30-day mortality in patients with candidemia were urinary catheters use (adjusted hazard ratio [HR] = 2.94; 95% confidence interval [CI] = 1.48-5.87; P = 0.002) and severe sepsis/septic shock (adjusted HR = 2.10; 95% CI = 1.20-3.65; P = 0.009). IDC was associated with a 46% reduction in 30-day mortality (adjusted HR = 0.54; 95% CI = 0.32-0.90; P = 0.017).

CONCLUSION: IDC was independently associated with a reduction in 30-day mortality. Only 44.5% of patients with candidemia in this cohort received IDC. Routine IDC should be actively considered for patients with candidemia.}, } @article {pmid31018850, year = {2019}, author = {Trinh, VQ and Benzerdjeb, N and Chagnon-Monarque, S and Dionne, N and Delouya, G and Kougioumoutzakis, A and Sirois, J and Albadine, R and Latour, M and Mes-Masson, AM and Hovington, H and Bergeron, A and Zorn, KC and Fradet, Y and Saad, F and Taussky, D and Trudel, D}, title = {Retrospective study on the benefit of adjuvant radiotherapy in men with intraductal carcinoma of prostate.}, journal = {Radiation oncology (London, England)}, volume = {14}, number = {1}, pages = {60}, pmid = {31018850}, issn = {1748-717X}, mesh = {Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Prognosis ; Prostatic Neoplasms/pathology/*radiotherapy ; Radiotherapy, Adjuvant/*mortality ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an independent biomarker of recurrence and survival with particular treatment response, yet no study has tested its response to radiotherapy. The aim of our project was to test the impact of adjuvant radiotherapy (ART) in patients with localized to locally advanced prostate cancer (PC) and IDC-P.

MATERIALS AND METHODS: We performed a retrospective study of men with pT2-T3 PC treated by radical prostatectomy (RP) with or without ART, from two centres (1993-2015). Exclusion criteria were the use of another type of treatment prior to biochemical recurrence (BCR), and detectable prostate- specific antigen (PSA) following RP or ART. Primary outcome was BCR (2 consecutive PSA ≥ 0.2 ng/ml). Patients were grouped by treatment (RPonly/RP + ART), IDC-P status, and presence of high-risk features (HRF: Grade Groups 4-5, positive margins, pT3 stage).

RESULTS: We reviewed 293 RP specimens (median follow-up 99 months, 69 BCR). Forty-eight patients (16.4%) were treated by RP + ART. Multivariate Cox regression for BCR indicated that IDC-P had the strongest impact (hazard ratio [HR] = 2.39, 95% confidence interval [CI]:1.44-3.97), while ART reduced the risk of BCR (HR = 0.38, 95%CI: 0.17-0.85). Other HRF were all significant except for pT3b stage. IDC-P[+] patients who did not receive ART had the worst BCR-free survival (log-rank P = 0.023). Furthermore, IDC-P had the same impact on BCR-free survival as ≥1 HRF (log-rank P = 0.955).

CONCLUSION: Men with IDC-P who did not receive ART had the highest BCR rates, and IDC-P had the same impact as ≥1 HRF, which are often used as ART indications. Once validated, ART should be considered in patients with IDC-P.}, } @article {pmid31016756, year = {2019}, author = {Zenan, H and Zixiong, L and Zhicheng, Y and Mei, H and Xiongbin, Y and Tiantian, W and Min, D and Renbin, L and Changchang, J}, title = {Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.}, journal = {Journal of cellular physiology}, volume = {234}, number = {11}, pages = {20584-20602}, doi = {10.1002/jcp.28662}, pmid = {31016756}, issn = {1097-4652}, mesh = {Aging ; Biomarkers, Tumor ; Blood Platelets/classification/physiology ; Breast Neoplasms/*classification/*genetics/pathology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Leukocytes/*classification/*physiology ; Logistic Models ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.}, } @article {pmid31016232, year = {2019}, author = {Jones, EF and Ray, KM and Li, W and Chien, AJ and Mukhtar, RA and Esserman, LJ and Franc, BL and Seo, Y and Pampaloni, MH and Joe, BN and Hylton, NM}, title = {Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.}, journal = {NPJ breast cancer}, volume = {5}, number = {}, pages = {12}, pmid = {31016232}, issn = {2374-4677}, abstract = {Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted.}, } @article {pmid31012493, year = {2019}, author = {Shah, RB and Nguyen, JK and Przybycin, CG and Reynolds, JP and Cox, R and Myles, J and Klein, E and McKenney, JK}, title = {Atypical intraductal proliferation detected in prostate needle biopsy is a marker of unsampled intraductal carcinoma and other adverse pathological features: a prospective clinicopathological study of 62 cases with emphasis on pathological outcomes.}, journal = {Histopathology}, volume = {75}, number = {3}, pages = {346-353}, doi = {10.1111/his.13878}, pmid = {31012493}, issn = {1365-2559}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Needle ; Humans ; Male ; Middle Aged ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; }, abstract = {AIMS: Intraductal proliferations of the prostate with more complexity and/or cytological atypia than high-grade prostate intra-epithelial neoplasia (HGPIN), but falling short of intraductal carcinoma (IDC-P), are described as 'atypical intraductal proliferation' (AIP). When present in needle biopsy (NBX) without IDC-P, the clinical significance is not known.

METHODS AND RESULTS: Sixty-two NBX cases were diagnosed as AIP over 7 years with estimated incidence of 1%. AIP was characterised by loose cribriform architecture (90%) or non-cribriform architecture exhibiting significant nuclear atypia that fell short of IDC-P. Fifty patients had concomitant PCa (20% grade group (GG) 1, 48% GG2, 14% GG3, 8% GG4 and 10% GG 5), and 12 had AIP alone. Of 40 patients who were candidates for no therapy (AIP alone) or active surveillance (AIP with GG1 or GG2 PCa without cribriform pattern 4), 20 had subsequent follow-up pathology [seven NBXs and 13 radical prostatectomy (RP)]. Of the 12 AIP only patients, six had a subsequent biopsy diagnosis of: benign prostate (two), IDC-P with PCa (one) and PCa (three). One or more adverse pathological features at subsequent RP were present in 93% of patients with AIP and GG1 or GG2 PCa, defined as: GG ≥ 3 (15%), IDC-P (77%), cribriform Gleason pattern 4 (69%), pT3a (77%) or pT3b (8%).

CONCLUSIONS: AIP in NBX may be a marker of unsampled IDC-P and/or other adverse pathological features in suspected low- to intermediate-risk PCa. AIP should be considered distinct from HGPIN for risk assessment and warrant consideration for further work-up to detect unsampled high-risk PCa.}, } @article {pmid31011322, year = {2019}, author = {Mouchli, M and Grider, DJ and Yeaton, P}, title = {Gallbladder Metastases: A Report of Two Cases.}, journal = {Case reports in oncology}, volume = {12}, number = {1}, pages = {235-240}, pmid = {31011322}, issn = {1662-6575}, abstract = {INTRODUCTION: Metastasis to the gallbladder is not common and usually manifests an advanced stage of malignancy. Herein, we report a case of triple negative high grade invasive ductal carcinoma of breast with a metastatic lesion to the gallbladder.

CASE PRESENTATION: The patient is a 52-year-old female diagnosed with invasive ductal carcinoma treated with mastectomy and chemotherapy. After 12 months, she presented to the emergency department with right upper quadrant pain and elevated liver chemistries. Abdominal enhanced computed tomography showed periportal and gallbladder wall edema. After cholecystectomy, the resected gallbladder was histologically considered to be a metastatic lesion arising from the primary lung cancer. The second case describes a case of a 77-year-old woman with multiple co-morbidities who presented to the hospital with sepsis secondary to biliary source. Abdominal enhanced computed tomography findings were concerning for acute cholecystitis. After cholecystectomy, the pathology of the resected gallbladder demonstrated cholecystitis and plasmacytoma.

CONCLUSION: The atypical presentation of gallbladder metastases could mislead treating providers. The diagnosis might alter management decisions and prognosis.}, } @article {pmid31004170, year = {2019}, author = {Harbertson, J and Scott, PT and Lemus, H and Michael, NL and Hale, BR}, title = {Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.}, journal = {Military medicine}, volume = {184}, number = {11-12}, pages = {e693-e700}, doi = {10.1093/milmed/usz070}, pmid = {31004170}, issn = {1930-613X}, mesh = {Adult ; Alcohol Drinking/adverse effects/epidemiology/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Disorders/*diagnosis/epidemiology/psychology ; Middle Aged ; Military Personnel/psychology/*statistics & numerical data ; Risk Factors ; Risk-Taking ; Sexual Behavior/*psychology ; Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology ; Ships/statistics & numerical data ; United States/epidemiology ; }, abstract = {INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.

MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).

RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.

CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.}, } @article {pmid31004098, year = {2019}, author = {Zinger, E and Gueijman, A and Obolski, U and Ram, Y and Ruby, E and Binder, M and Yechieli, N and Ohad, N and Hadany, L}, title = {Less fit Lamium amplexicaule plants produce more dispersible seeds.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6299}, pmid = {31004098}, issn = {2045-2322}, mesh = {Animals ; Ants/physiology ; Lamiaceae/*physiology ; Seed Dispersal/*physiology ; Seeds/*physiology ; }, abstract = {Theory predicts that less fit individuals would disperse more often than fitter ones (Fitness Associated Dispersal, FAD hypothesis). To test this prediction under laboratory conditions, an entire life cycle of Lamium amplexicaule plants and the preferences of its dispersal agent, Messor ebeninus ants, were tracked. Characterization of individual L. amplexicaule plant revealed high variability in spot cover on the surface of the seeds, where less fit plants produce "unspotted seeds" (see Fig. 1 in Introduction). Unspotted L. amplexicaule seeds showed higher variation in germination time and lower germination rate. Moreover, M. ebeninus ants preferably collected these unspotted seeds. Our results show that low fitness L. amplexicaule plants produce seeds with higher potential for dispersal, supporting the FAD hypothesis in a plant-animal system.}, } @article {pmid30998679, year = {2019}, author = {Pare, R and Soon, PS and Shah, A and Lee, CS}, title = {Differential expression of senescence tumour markers and its implications on survival outcomes of breast cancer patients.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0214604}, pmid = {30998679}, issn = {1932-6203}, mesh = {Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/mortality/*pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Tumor Necrosis Factor Decoy Receptors/metabolism ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Proteins/metabolism ; }, abstract = {Breast cancer is a heterogeneous disease displaying different histopathological characteristics, molecular profiling and clinical behavior. This study describes the expression patterns of senescence markers P53, DEC1 and DCR2 and assesses their significance on patient survival as a single or combined marker with P16 or P14 using breast cancer progression series. One thousand and eighty (1080) patients with primary invasive ductal carcinoma, no special type, were recruited through an 11-year retrospective study period. We constructed tissue microarrays of normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma from each patient and performed immunohistochemical staining to study the protein expression. Statistical analysis includes Pearson chi-square, Kaplan-Meier log ran test and Cox proportional hazard regression were undertaken to determine the associations and predict the survival outcomes. P53, DEC1 and DCR2 expression correlated significantly with normal, benign, premalignant and malignant tissues with (p<0.05). The expression profile of these genes increases from normal to benign to premalignant and plateaued from premalignant to malignant phenotype. There is a significant association between P53 protein expression and age, grade, staging, lymphovascular invasion, estrogen receptor, progesterone receptor and HER2 whereas DCR2 protein expression significantly correlated with tumour grade, hormone receptors status and HER2 (p<0.05 respectively). P53 overexpression correlated with increased risk of relapse (p = 0.002) specifically in patients who did not receive hormone therapy (p = 0.005) or chemotherapy (p<0.0001). The combination of P53+/P16+ is significantly correlated with poor overall and disease-free survival, whereas a combination of P53+/P14+ is associated with worse outcome in disease-free survival (p<0.05 respectively). P53 overexpression appears to be a univariate predictor of poor disease-free survival. The expression profiles of DEC1 and DCR2 do not appear to correlate with patient survival outcomes. The combination of P53 with P16, rather P53 expression alone, appears to provide more useful clinical information on patient survival outcomes in breast cancer.}, } @article {pmid30997786, year = {2019}, author = {Oğuz Kapicibasi, H}, title = {The role of mediastinoscopy in the diagnosis of thoracic disease: 107-case analysis.}, journal = {Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina}, volume = {16}, number = {2}, pages = {}, doi = {10.17392/1001-19}, pmid = {30997786}, issn = {1840-2445}, abstract = {Aim To evaluate the efficacy, safety and feasibility of mediastinoscopy in 107 cases with mediastinal lesions that could not be diagnosed histopathologically with other methods. Methods A total of 107 cases (73 males, 34 females; mean age 57.4, range 30-88 years) with mediastinal lymphadenopathy, who underwent mediastinoscopy between 12 September 2012 and 29 November 2018 were examined retrospectively. The cases were evaluated in terms of age, gender, complaint, operation time, histopathological diagnosis, postoperative morbidity and mortality parameters. Results Upon histopathological examination 32 (30%) patients were diagnosed with lung cancer metastasis (N2 stage), which was the most common diagnosis. With this diagnosis unnecessary thoracotomy was prevented. In patients with pathological lymphadenopathy found by imaging histopathological results were examined to evaluate the presence of N2 stage. In 25 (23.5%) cases biopsy results were reported as reactive lymph nodes. In addition, 23 (21.4%) patients had sarcoidosis, 16 (15%) had tuberculosis lymphadenitis, seven (6.5%) had lymphoma, one of each (0.9%) had benign epithelial cyst (0.9%), malign epithelial tumour (invasive ductal carcinoma of breast), chronic lymphocytic leukaemia (CLL), and adenocarcinoma metastasis (renal cell cancer). Conclusion When other non-invasive procedures are ineffective, mediastinoscopy is an efficient diagnostic method with high diagnostic value, which is applicable also in places other than advanced centres, with low morbidity and mortality.}, } @article {pmid30997623, year = {2019}, author = {Flores-Díaz, D and Arce, C and Flores-Luna, L and Reynoso-Noveron, N and Lara-Medina, F and Matus, JA and Bargallo-Rocha, E and Pérez, V and Villarreal-Garza, C and Cabrera-Galeana, P and Mohar, A}, title = {Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {176}, number = {1}, pages = {243-249}, doi = {10.1007/s10549-019-05234-8}, pmid = {30997623}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/epidemiology/*mortality/*pathology/therapy ; Carcinoma, Lobular/epidemiology/*mortality/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Mexico/epidemiology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Population Surveillance ; Young Adult ; }, abstract = {PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC).

METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis.

RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02).

CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.}, } @article {pmid30995855, year = {2019}, author = {Mikudova, V and Rejlekova, K and Gyarfas, J and Oravcova, I and Chovanec, M and Mardiak, J and Mego, M}, title = {Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy - a Case Report.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {2}, pages = {139-142}, doi = {10.14735/amko2018139}, pmid = {30995855}, issn = {1802-5307}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Injections, Spinal ; Meningeal Neoplasms/*drug therapy/secondary ; Prognosis ; }, abstract = {BACKGROUND: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months.

METHODS: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival.

RESULTS: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM.

CONCLUSION: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.}, } @article {pmid30993692, year = {2019}, author = {Khani, F and Wobker, SE and Hicks, JL and Robinson, BD and Barbieri, CE and De Marzo, AM and Epstein, JI and Pritchard, CC and Lotan, TL}, title = {Intraductal carcinoma of the prostate in the absence of high-grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations.}, journal = {The Journal of pathology}, volume = {249}, number = {1}, pages = {79-89}, doi = {10.1002/path.5283}, pmid = {30993692}, issn = {1096-9896}, mesh = {Aged ; Biomarkers, Tumor/*genetics ; Carcinoma in Situ/classification/*genetics/pathology ; Carcinoma, Ductal/classification/*genetics/pathology ; DNA Copy Number Variations ; Gene Dosage ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinases/genetics ; *Mutation ; Neoplasm Grading ; Neoplasm Invasiveness ; *Oncogenes ; PTEN Phosphohydrolase/genetics ; Phenotype ; Phosphatidylinositol 3-Kinase/genetics ; Prostatic Neoplasms/classification/*genetics/pathology ; Transcriptional Regulator ERG/genetics ; Transcriptome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) most often appears associated with high-grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC-P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low-grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC-P (iIDC-P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC-P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC-P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC-P alterations were similar to those previously described in high-grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC-P (BRCA2, CHEK2, CDK12) and other known PCa-associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC-P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC-P and the low-grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC-P in four. Despite a CNA profile similar to conventional PCa, iIDC-P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC-P is not likely a precursor to the associated low-grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid30992422, year = {2019}, author = {Aldossary, MY and Alquraish, F and Alazhri, J}, title = {A Case of Locally Advanced Breast Cancer in a 59-Year-Old Man Requiring a Modified Approach to Management.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {531-536}, pmid = {30992422}, issn = {1941-5923}, mesh = {Biopsy, Needle ; Breast Neoplasms, Male/drug therapy/*pathology/radiotherapy/*surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/radiotherapy/*surgery ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Male ; Mastectomy, Radical/*methods ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rare Diseases ; Tamoxifen/*therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND Male breast cancer is rare, accounting for approximately 1% of all malignancies in men. The lack of awareness of this rare cancer results in delayed diagnosis and its aggressive behavior can result in poor prognosis. This report is of a case of locally advanced, high-grade breast cancer in a 59-year-old man who was reluctant to undergo diagnostic procedures, and describes the approach to clinical management. CASE REPORT A 59-year-old man presented with a large left breast mass with enlarged axillary lymph nodes. The patient had ignored the mass and declined all diagnostic procedures. After modifying the diagnostic workup and involving a psychiatrist, the patient agreed to undergo a modified radical mastectomy. Histopathology showed a high-grade invasive ductal carcinoma with lymph node metastasis. The breast cancer was triple-positive for human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Adjuvant treatment included herceptin, tamoxifen, and radiation therapy. CONCLUSIONS This case demonstrates the importance of raising public awareness of breast cancer in men, and to assess and overcome the factors leading to delay in accessing medical attention. In challenging cases, modifying the diagnostic workup and the treatment approach with the least deviation from the standard of care, including counseling may be required.}, } @article {pmid30989460, year = {2019}, author = {Lee, J and Kim, HE and Song, YS and Cho, EY and Lee, A}, title = {miR-106b-5p and miR-17-5p could predict recurrence and progression in breast ductal carcinoma in situ based on the transforming growth factor-beta pathway.}, journal = {Breast cancer research and treatment}, volume = {176}, number = {1}, pages = {119-130}, pmid = {30989460}, issn = {1573-7217}, support = {NRF-2017R1D1A1B03034165//National Research Foundation of Korea/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Recurrence, Local ; RNA Interference ; Signal Transduction ; Transcriptome ; Transforming Growth Factor beta/*metabolism ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to identify potential markers predicting recurrence.

METHODS: Forty archival tissues diagnosed as primary or recurrent DCIS and DCIS adjacent to IDC were analyzed. MiRNA hierarchical clustering showed up-regulation of miR-17-5p and miR-106b-5p in recurrent DCIS and DCIS adjacent to IDC. Target genes were predicted based on pre-formed miRNA databases and PanCancer Pathway panel. MiRNAs were transfected into MCF-10A and MCF-7 cells; western blot analysis was performed with MCF-7 cell line to evaluate the effects on TGF-β downstream pathway.

RESULTS: miRNA hierarchical clustering showed 17 dysregulated miRNAs, including miR-17-5p and miR-106b-5p. Based on miRNA database and nCounter Pancancer pathway analysis, TGFβRII was selected as target of miR-106b-5p and miR-17-5p. MiR-106b-5p- and miR-17-5p-transfected MCF-7 cells showed decreased expression of TGFβRII, especially in cells transfected with both miRNAs.

CONCLUSION: miR-106b-5p and miR-17-5p might have a role in breast cancer recurrence and progression by suppressing TGF-β activity, leading to early breast cancer carcinogenesis.}, } @article {pmid30987214, year = {2019}, author = {Raplee, ID and Evsikov, AV and Marín de Evsikova, C}, title = {Aligning the Aligners: Comparison of RNA Sequencing Data Alignment and Gene Expression Quantification Tools for Clinical Breast Cancer Research.}, journal = {Journal of personalized medicine}, volume = {9}, number = {2}, pages = {}, pmid = {30987214}, issn = {2075-4426}, support = {Fund for Science Epigenetics & Functional Genomics Lab//Impact Assests/ ; }, abstract = {The rapid expansion of transcriptomics and affordability of next-generation sequencing (NGS) technologies generate rocketing amounts of gene expression data across biology and medicine, including cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between two predominant programs for read alignment, HISAT2, and STAR, and two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from breast cancer progression series, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners' performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes, with edgeR producing more conservative, though shorter, lists of genes. Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO terms identified among differentially expressed genes by edgeR versus DESeq2. As transcriptomics of FFPE samples becomes a vanguard of precision medicine, choice of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.}, } @article {pmid30985953, year = {2019}, author = {Erro, R and Picillo, M and Amboni, M and Savastano, R and Scannapieco, S and Cuoco, S and Santangelo, G and Vitale, C and Pellecchia, MT and Barone, P}, title = {Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.}, journal = {European journal of neurology}, volume = {26}, number = {9}, pages = {1212-1218}, doi = {10.1111/ene.13968}, pmid = {30985953}, issn = {1468-1331}, mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Hypokinesia/etiology/*physiopathology ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.

METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years.

RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.

CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.}, } @article {pmid30982780, year = {2019}, author = {Ren, W and Guan, W and Zhang, J and Wang, F and Xu, G}, title = {Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development.}, journal = {Aging}, volume = {11}, number = {7}, pages = {2151-2176}, pmid = {30982780}, issn = {1945-4589}, mesh = {Adult ; Aged ; Binding, Competitive ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; MicroRNAs/genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Pyridoxaminephosphate Oxidase/antagonists & inhibitors/genetics/*metabolism ; RNA, Long Noncoding/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tumor Stem Cell Assay ; }, abstract = {Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.}, } @article {pmid30967550, year = {2019}, author = {Heeren, N and Fishman, T}, title = {A database seed for a community-driven material intensity research platform.}, journal = {Scientific data}, volume = {6}, number = {1}, pages = {23}, pmid = {30967550}, issn = {2052-4463}, abstract = {The data record contains Material Intensity data for buildings (MI). MI coefficients are often used for different types of analysis of socio-economic systems and in particular for environmental assessments. Until now, MI values were compiled and reported ad-hoc with few cross-study comparisons. We extracted and converted more than 300 material intensity data points from 33 studies and provide the results in a comprehensive and harmonized database. Material intensity is reported as kilograms per gross floor area for 32 materials as primary data points. Furthermore, we augmented the data with secondary attributes for regional information, such as climate and socioeconomic indicators. The data are hosted on the version control platform GitHub using accessible data formats and providing detailed contribution guidelines. This "database seed" facilitates data analysis, accessibility, and future data contributions by the research community. In the Technical Validation we illustrate that consistency of the data and opportunities for further analysis. This database can serve scientists from various disciplines as a benchmark to determine typical ranges and identify outliers.}, } @article {pmid30963646, year = {2019}, author = {Tollow, P and Williams, VS and Harcourt, D and Paraskeva, N}, title = {"It felt like unfinished business, it feels like that's finished now": Women's experiences of decision making around contralateral prophylactic mastectomy (CPM).}, journal = {Psycho-oncology}, volume = {28}, number = {6}, pages = {1328-1334}, doi = {10.1002/pon.5086}, pmid = {30963646}, issn = {1099-1611}, mesh = {Adult ; Aged ; Breast Neoplasms/*psychology/*surgery ; *Decision Making ; Female ; Humans ; Mastectomy/*psychology ; Middle Aged ; Prophylactic Mastectomy/*psychology ; Qualitative Research ; United Kingdom ; }, abstract = {OBJECTIVE: Increasing numbers of women in the United Kingdom are choosing to have a contralateral prophylactic mastectomy (CPM) after diagnosis of breast cancer. Whilst research suggests that many experience high rates of psychological well-being after CPM, professional guidelines suggest CPM is "not required" for the majority of unilateral breast cancer patients, and some individuals consider the surgery to be controversial. Existing research has explored patients' reasons for seeking CPM; however, little is known about their experiences of decision making. This study aimed to investigate women's experiences of decision making around CPM in the United Kingdom.

METHODS: Semistructured qualitative interviews were conducted with 27 women, recruited through breast cancer support charities. All participants had CPM in the United Kingdom after a diagnosis of unilateral breast cancer, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma. Data were analysed using thematic analysis.

RESULTS: Two main themes were generated from the analytic process: "sanity check" ("battling for CPM," "feeling stigmatised," "seeking similar others") and "reclaiming the body" ("being true to self," "moving forward"). Women described defending their decision to have CPM, concerns that their thoughts about surgery may be considered "abnormal," and seeking support from peers. The decision to have CPM was discussed in terms of their future relationship with their body and moving forward after cancer.

CONCLUSIONS: This study highlights the importance of interactions with health care professionals in the decision-making experience, the role of peer support, and the need to fully understand the potentially complex and multifaceted nature of each woman's decision to seek CPM.}, } @article {pmid30962690, year = {2019}, author = {Wu, SG and Zhang, WW and Wang, J and Dong, Y and Chen, YX and He, ZY}, title = {Effect of 21-gene recurrence score in decision-making for surgery in early stage breast cancer.}, journal = {OncoTargets and therapy}, volume = {12}, number = {}, pages = {2071-2078}, pmid = {30962690}, issn = {1178-6930}, abstract = {AIM: We aimed to assess the role of 21-gene recurrence score (RS) in the decision-making for surgical treatment in early stage breast cancer and compared the outcomes between breast-conserving surgery (BCS) and mastectomy (MAST) among various 21-gene RS groups.

METHODS: We included patients with stage T1-2M0M0 and estrogen receptor-positive breast invasive ductal carcinoma who underwent BCS + radiotherapy or MAST between 2004 and 2012 as part of the Surveillance, Epidemiology, and End Results program. Data were analyzed using binomial logistic regression, multivariate Cox proportional hazards models, and propensity score matching (PSM).

RESULTS: We enrolled 34,447 patients including 22,681 (65.8%) and 11,766 (34.2%) who underwent BCS and MAST, respectively. Patients with high-risk RS were more likely to receive MAST. Multivariate analysis indicated that patients with intermediate-risk (P<0.001) and high-risk (P<0.001) RS had poor breast cancer-specific survival (BCSS), as compared to those with low-risk RS. Moreover, patients who underwent MAST also exhibited poor BCSS (P<0.001), as compared to those who underwent BCS. In low-risk (P<0.001) and intermediate-risk (P=0.020) RS groups, patients who underwent MAST had poor BCSS, as compared to those treated with BCS. However, BCSS was comparable between patients who underwent MAST and BCS (P=0.952); similar trends were also observed after PSM.

CONCLUSION: The 21-gene RS may impact the decision-making for surgery in early stage breast cancer. Our study provides additional support for a shared decision-making process for BCS when both local management options are appropriate choices regardless of the 21-gene RS.}, } @article {pmid30959550, year = {2019}, author = {Deva Magendhra Rao, AK and Patel, K and Korivi Jyothiraj, S and Meenakumari, B and Sundersingh, S and Sridevi, V and Rajkumar, T and Pandey, A and Chatterjee, A and Gowda, H and Mani, S}, title = {Identification of lncRNAs associated with early-stage breast cancer and their prognostic implications.}, journal = {Molecular oncology}, volume = {13}, number = {6}, pages = {1342-1355}, pmid = {30959550}, issn = {1878-0261}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Gene Regulatory Networks/genetics ; Humans ; Prognosis ; RNA, Long Noncoding/genetics/*metabolism ; Sequence Analysis, RNA ; }, abstract = {Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was performed on six invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, seven ductal carcinoma in situ tissues, and five apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (~ 58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was performed in n = 52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3, and FAM83H-AS1). We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and report that overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the downregulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in vitro silencing experiments and pyrosequencing.}, } @article {pmid30955173, year = {2020}, author = {Shams, R and Seifi-Alan, M and Bandehpour, M and Omrani, MD and Ghafouri-Fard, S}, title = {C-X-C Chemokine Receptor Type 7 (CXCR-7) Expression in Invasive Ductal Carcinoma of Breast in Association with Clinicopathological Features.}, journal = {Pathology oncology research : POR}, volume = {26}, number = {2}, pages = {1015-1020}, doi = {10.1007/s12253-019-00649-6}, pmid = {30955173}, issn = {1532-2807}, support = {105//Shahid Beheshti University of Medical Sciences/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; MicroRNAs/*metabolism ; Middle Aged ; Receptors, CXCR/*biosynthesis ; }, abstract = {C-X-C chemokine receptor type 7 (CXCR-7) is an atypical receptor for chemokines whose role in different stages of carcinogenesis has been evaluated in breast cancer cell lines and animal models. Moreover, it has been demonstrated to be a target of regulation by the tumor suppressor microRNA (miR)-100. In the present study, we assessed CXCR-7 expression in 60 breast cancer patients in association with clinicopathological and demographic data of patients. We also extracted the results of our previous work on miR-100 expression in the same cohort of patients to assess the correlation between miR-100 and CXCR-7 expression levels. Transcript levels of CXCR-7 were significantly higher in tumoral tissues compared with adjacent non-cancerous tissues (ANCTs) (Tumoral vs. ANCTs: 3.64 ± 1.8 vs. 0.73 ± 1.3, P = 0.000). A significant negative correlation was detected between CXCR-7 protein and miR-100 transcript levels (r = -0.526, P < 0.05). High CXCR-7 mRNA levels were significantly associated with tumor size (P = 0.01). Besides, high protein levels were more prevalent in higher TNM stages (P = 0.000). Moreover, high CXCR-7 protein levels were significantly associated with ER (P = 0.005) and PR (P = 0.02) status. The present work provides further evidence for the role of CXCR-7 in breast cancer and proposes the elimination of inhibitory effects of miR-100 on CXCR-7 expression as a mechanism for its up-regulation in breast cancer tissues.}, } @article {pmid30951802, year = {2020}, author = {Tiiri, E and Luntamo, T and Mishina, K and Sillanmäki, L and Brunstein Klomek, A and Sourander, A}, title = {Did Bullying Victimization Decrease After Nationwide School-Based Antibullying Program? A Time-Trend Study.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {59}, number = {4}, pages = {531-540}, doi = {10.1016/j.jaac.2019.03.023}, pmid = {30951802}, issn = {1527-5418}, mesh = {Adolescent ; *Bullying ; *Crime Victims ; Cross-Sectional Studies ; Female ; Humans ; Male ; Schools ; Students ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: We assessed changes in traditional and cyberbullying victimization, and their associations with mental health, before and after the introduction of a nationwide antibullying program in Finnish schools in 2009.

METHOD: This time-trend assessment comprised two methodologically identical cross-sectional survey studies, with 2,061 adolescents in 2008 (response rate 90.2%) and 1,936 in 2014 (91.8%). Their mean age was 14.4 years. They completed questionnaires about traditional and cyberbullying, mental health, and perceptions of school safety. Odds ratios (OR) and 95% CIs are presented with 2008 as the reference year.

RESULTS: From 2008 to 2014, traditional victimization decreased from 28.9% to 19.1% (odds ratio [OR] = 0.5, 95% CI = 0.4-0.7) among boys and from 23.2% to 17.4% (OR = 0.7, 95% CI = 0.6-0.9) among girls. Cyberbullying victimization remained fairly stable at 3.3% and 3.0% (OR = 0.7, 95% CI = 0.4-1.2) for boys and at 2.7% and 4.1% (OR = 1.4, 95% CI = 0.9-2.4) for girls. Combined traditional and cyberbullying victimization decreased from 6.1% to 3.9% (OR = 0.5, 95% CI = 0.4-0.8) among boys and from 7.5% to 6.7% (OR = 0.8, 95% CI = 0.6-1.2) among girls. Those experiencing both traditional and cyberbullying reported the highest mental health problems. Perceived school safety improved among boys, but not among girls. Both boys and girls reported greater efforts by teachers and fellow students to stop bullying.

CONCLUSION: Combined traditional and cyberbullying victimization was an indicator of comorbid mental health problems. Interventions that target both types of bullying, and that are integrated with mental health promotion, are needed.}, } @article {pmid30950444, year = {2019}, author = {Reddy, A and Mullapudi, NA and Kabeer, KK and Nimmagadda, R and Radhakrishna, S}, title = {Treatment of elderly breast cancer patients in a breast center in India.}, journal = {Indian journal of cancer}, volume = {56}, number = {1}, pages = {45-49}, doi = {10.4103/ijc.IJC_237_18}, pmid = {30950444}, issn = {1998-4774}, mesh = {Aged ; Breast Neoplasms/metabolism/pathology/*therapy ; Cancer Care Facilities/*statistics & numerical data ; Carcinoma, Ductal, Breast/metabolism/pathology/*therapy ; Case-Control Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; India ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Treatment Outcome ; }, abstract = {CONTEXT: The management of breast cancer in older patients is challenging due to factors such as comorbidities, limited mobility, functional dependence, cognitive functions, and socioeconomic aspects. Data about the outcomes in elderly patients with breast cancer in our country are sparse.

AIMS: The aim of this study was to evaluate and compare the clinical and pathological variables, treatment, and survival outcomes of elderly women (those of 70 years and above) with women under 50 years and those between the ages of 50 and 69 years treated at our center.

SUBJECTS AND METHODS: Prospectively collected clinical and pathological data from January 2007 to December 2014 were recorded and entered into OncoCollect™ software. Statistical analysis was done using Microsoft R Open software. Survival analysis was estimated using Kaplan-Meier curves.

RESULTS: A total of 1226 Stage I-III breast cancer patients were treated between January 2007 and December 2014. Of these, 11.3% (139) were aged 70 years and above. Invasive ductal carcinoma was predominant and majority had Stage II disease and grade 1 tumors. Receptor positivity was observed in 79% of elderly patients and 9% had triple-negative disease. Primary hormone therapy was given to 7% of the patients and chemotherapy was administered to 12%. The 5-year overall survival for patients 70 years and older is 85%.

CONCLUSIONS: Elderly patients are more likely to have an indolent course with low grade and estrogen receptor-positive tumors. For healthy older women, treatment according to standard guidelines including surgery, chemotherapy, and radiation should be followed. However, for those who are unfit and cannot tolerate surgery, primary endocrine therapy is a suitable option.}, } @article {pmid30947557, year = {2020}, author = {Te'Eni-Harari, T and Eyal, K}, title = {The Role of Food Advertising in Adolescents' Nutritional Health Socialization.}, journal = {Health communication}, volume = {35}, number = {7}, pages = {882-893}, doi = {10.1080/10410236.2019.1598737}, pmid = {30947557}, issn = {1532-7027}, mesh = {Adolescent ; *Adolescent Behavior ; *Advertising ; Female ; Food ; Humans ; Male ; Peer Group ; Socialization ; }, abstract = {Adolescents are heavily exposed to food advertising in their daily lives. Food ads tend to juxtapose unhealthy food products with overly thin models who promote these foods. This paradoxical presentation of food and body raises important questions about adolescents' perceptions of food ads and the body, as part of the larger realm of nutritional health. The study sheds light on adolescents' nutritional health socialization by exploring the role of food advertising as it intersects with other socialization agents, namely parents and peers. Adolescent's perceptions of and reactions to food ads, and the food products and models in these ads, are examined using the media practice model as the theoretical framework. In-depth interviews were conducted with 82 adolescents in middle- and high-school, taking into consideration their development, heightened vulnerability to messages about the body and appearances, and their lived experiences. The study's findings suggest that adolescents, though skeptical of ads, internalize the mediated thin ideal and expect models in ads to be thin, beautiful, and famous. Parents emerged as positive role models for nutritional health whereas peers are more paradoxical, emphasizing the importance of exercising along with a socially-oriented consumption of junk food. Socialization messages from parents, peers, and the media interact in shaping adolescents' reactions to food ads. Only minimal gender differences were found in adolescents' reactions to food ads and their approach to nutritional health. Mostly, female models are expected to meet more stringent standards of thinness and beauty than male models, especially among female adolescents.}, } @article {pmid30943919, year = {2019}, author = {Campbell, EJ and Dachs, GU and Morrin, HR and Davey, VC and Robinson, BA and Vissers, MCM}, title = {Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {307}, pmid = {30943919}, issn = {1471-2407}, support = {R1512//Canterbury Medical Research Foundation/ ; R1512//New Zealand Breast Cancer Foundation/ ; }, mesh = {Antigens, Neoplasm/genetics/*metabolism ; Ascorbic Acid/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carbonic Anhydrase IX/genetics/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins/genetics/*metabolism ; Retrospective Studies ; Survival Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/genetics/*metabolism ; }, abstract = {BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.

METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.

RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.

CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.}, } @article {pmid30938998, year = {2019}, author = {Xie, X and Zhang, Z and Zhang, J and Hou, L and Li, Z and Li, G}, title = {Impressive Proton Conductivities of Two Highly Stable Metal-Organic Frameworks Constructed by Substituted Imidazoledicarboxylates.}, journal = {Inorganic chemistry}, volume = {58}, number = {8}, pages = {5173-5182}, doi = {10.1021/acs.inorgchem.9b00274}, pmid = {30938998}, issn = {1520-510X}, abstract = {There is great interest in the promising applications of proton-conductive metal-organic frameworks (MOFs) in the field of electrochemistry. Thus, seeking more types of MOFs with high proton conductivity is of great importance. Herein, we designed and prepared two substituted imidazoledicarboxylate-based MOFs, {[Cd(p-TIPhH2IDC)2]·H2O} n [1; p-TIPhH3IDC = 2- p-(1 H-1,2,4-triazolyl)phenyl-1 H-4,5-imidazoledicarboxylic acid] and [Sr(DMPhH2IDC)2] n [2; DMPhH3IDC = 2-(3,4-dimethylphenyl)-1 H-imidazole-4,5-dicarboxylic acid], and fully explored their water-assisted proton conduction. The best conductivity for 1 of 1.24 × 10[-4] S·cm[-1] is higher than that of most previous conductive Cd-MOFs under similar conditions. 2 has the highest conductivity (0.92 × 10[-3] S·cm[-1]) among the reported conductive Sr-MOFs. Via structural analysis, Ea values, water vapor adsorptions, and powder X-ray diffraction and scanning electron microscopy tests, reasonable proton pathways and conduction mechanisms were highlighted. It should be emphasized that the N-heterocyclic units (imidazole and triazole) and carboxyl and hydrogen-bonding networks in the frameworks all play crucial roles in the transmission of proton conductivity. Our research offers more choice for the preparation of desired proton-conductive materials.}, } @article {pmid30936719, year = {2019}, author = {Zhang, L and Hao, C and Wu, Y and Zhu, Y and Ren, Y and Tong, Z}, title = {Microcalcification and BMP-2 in breast cancer: correlation with clinicopathological features and outcomes.}, journal = {OncoTargets and therapy}, volume = {12}, number = {}, pages = {2023-2033}, pmid = {30936719}, issn = {1178-6930}, abstract = {BACKGROUND: Microcalcification is a very important diagnostic information in breast cancer. The purpose of this study was to determine the relationship of clinicopathological features and prognosis of breast cancer with microcalcification and to detect biomarkers related to the possible mechanisms of microcalcifications.

PATIENTS AND METHODS: All 529 subjects with microcalcifications were selected from patients who had been examined using breast mammography. The control group did not have detectable microcalcifications, and was matched in a ratio of 1:3. The clinicopathological factors, progression-free survival (PFS), and overall survival were evaluated by SPSS.

RESULTS: There was a significant difference in tumor size between the two groups, with larger tumors in the calcification group than the control group, and the proportion of patients in the calcification group with tumors of >5 cm was 20.4% vs 17.2% in the control group (P=0.041). The proportion of patients with lymph node metastasis in the calcification group was higher than that of the control group (35% vs 27.9%, P=0.027). The recurrence rate in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) patients with microcalcification was higher than that in the control group (P=0.035 and 0.044). BMP-2 expression was higher in breast cancer tissues, especially in breast cancer tissues with microcalcifications. The recurrence rate in the BMP-2(+) group was higher than that in the BMP-2(-) group both in DCIS and IDC (P=0.044 and 0.049). Microcalcifications and the positive expression of BMP-2 were independent factors affecting the PFS of the breast cancer patients.

CONCLUSION: Through the analysis of this study, it was found that the prognosis of the patients with microcalcification was relatively poor. BMP-2 was highly expressed in the breast cancer with microcalcification and was associated with poor prognosis.}, } @article {pmid30926444, year = {2019}, author = {Herent, P and Schmauch, B and Jehanno, P and Dehaene, O and Saillard, C and Balleyguier, C and Arfi-Rouche, J and Jégou, S}, title = {Detection and characterization of MRI breast lesions using deep learning.}, journal = {Diagnostic and interventional imaging}, volume = {100}, number = {4}, pages = {219-225}, doi = {10.1016/j.diii.2019.02.008}, pmid = {30926444}, issn = {2211-5684}, mesh = {Algorithms ; Breast/*diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Contrast Media ; Datasets as Topic ; *Deep Learning ; Female ; Gadolinium ; Humans ; *Magnetic Resonance Imaging ; }, abstract = {PURPOSE: The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions.

MATERIALS AND METHODS: We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores.

RESULTS: We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set.

CONCLUSION: This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort.}, } @article {pmid30921631, year = {2019}, author = {Dekel, S and Ein-Dor, T and Ruohomäki, A and Lampi, J and Voutilainen, S and Tuomainen, TP and Heinonen, S and Kumpulainen, K and Pekkanen, J and Keski-Nisula, L and Pasanen, M and Lehto, SM}, title = {The dynamic course of peripartum depression across pregnancy and childbirth.}, journal = {Journal of psychiatric research}, volume = {113}, number = {}, pages = {72-78}, doi = {10.1016/j.jpsychires.2019.03.016}, pmid = {30921631}, issn = {1879-1379}, mesh = {Adult ; Cohort Studies ; Databases, Factual ; Depression, Postpartum/psychology ; Depressive Disorder/*psychology ; Female ; Finland ; Humans ; Mothers/*psychology ; Peripartum Period/*psychology ; Pregnancy ; Pregnancy Complications/*psychology ; Pregnancy Trimester, First ; Pregnancy Trimester, Third ; Psychiatric Status Rating Scales ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Peripartum depression (PPD) pertaining to depression in pregnancy and postpartum is one of the most common complications around childbirth with enduring adverse effects on mother and child health. Although psychiatric symptoms may improve or worsen over time, relatively little is known about the course of PPD symptoms and possible fluctuations.

METHODS: We applied a person-centered approach to examine PPD symptom patterns across pregnancy and childbirth. 824 women were assessed at three time points: first trimester (T1), third trimester (T2), and again at eight weeks (T3) postpartum. We assessed PPD symptoms, maternal mental health history, and childbirth variables.

RESULTS: Growth mixture modeling (GMM) analysis revealed four discrete PPD symptom trajectory classes including chronic PPD (1.1%), delayed (10.2%), recovered (7.2%), and resilient (81.5%). Delivery complications were associated with chronic PPD but also with the recovered PPD trajectory class. History of mental health disorders was associated with chronic PPD and the delayed PPD class.

CONCLUSION: The findings underscore that significant changes in a woman's depression level can occur across pregnancy and childbirth. While a minority of women experience chronic PDD, for others depression symptoms appear to significantly alleviate over time, suggesting a form of recovery. Our findings support a personalized medicine approach based on the woman's symptom trajectory. Future research is warranted to identify the mechanisms underlying modifications in PPD symptoms severity and those implicated in recovery.}, } @article {pmid30918897, year = {2019}, author = {van Oort, PM and Bos, LD and Póvoa, P and Ramirez, P and Torres, A and Artigas, A and Schultz, MJ and Martin-Loeches, I}, title = {Soluble urokinase plasminogen activator receptor for the prediction of ventilator-associated pneumonia.}, journal = {ERJ open research}, volume = {5}, number = {1}, pages = {}, pmid = {30918897}, issn = {2312-0541}, abstract = {INTRODUCTION: Diagnosing ventilator-associated pneumonia (VAP) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) has prognostic value in critically ill patients with systemic infection. We hypothesised that plasma suPAR levels accurately predict development of VAP.

METHODS: This observational, multicentre, prospective cohort study compared patients at risk for VAP with a control group. Plasma and tracheal aspirate samples were collected. Plasma suPAR levels were measured on the day of diagnosis and 3 days before diagnosis.

RESULTS: The study included 24 VAP patients and 19 control patients. The suPAR concentration measured 3 days before diagnosis was significantly increased in VAP patients versus matched samples of control patients (area under the receiver operating characteristic curve (AUC) 0.68, 95% CI 0.52-1.00; p=0.04). Similar results were found on the day of diagnosis (AUC 0.77, 95% CI 0.6-0.93; p=0.01). Plasma suPAR was significantly higher in deceased patients (AUC 0.79, 95% CI 0.57-1.00; p<0.001). Combining suPAR with the Clinical Pulmonary Infection Score, C-reactive protein and/or procalcitonin led to a significantly increased discriminative accuracy for predicting VAP and an increased specificity.

CONCLUSIONS: suPAR can be used to diagnose VAP with a fair diagnostic accuracy and has a moderate prognostic accuracy to be used in critically ill intensive care unit patients. Its performance improves when added to other clinically available biomarkers (C-reactive protein and procalcitonin) or scoring systems (Clinical Pulmonary Infection Score and Sepsis-related Organ Failure Assessment).}, } @article {pmid30916846, year = {2019}, author = {Leshem, R and van Lieshout, PHHM and Ben-David, S and Ben-David, BM}, title = {Does emotion matter? The role of alexithymia in violent recidivism: A systematic literature review.}, journal = {Criminal behaviour and mental health : CBMH}, volume = {29}, number = {2}, pages = {94-110}, doi = {10.1002/cbm.2110}, pmid = {30916846}, issn = {1471-2857}, mesh = {*Affective Symptoms ; Aggression/psychology ; Crime/*statistics & numerical data ; Criminals/*psychology ; *Emotions ; Humans ; Male ; *Recidivism ; Recurrence ; Risk Assessment ; Risk Factors ; Violence/*psychology/statistics & numerical data ; }, abstract = {BACKGROUND: Several variables have been evidenced for their association with violent reoffending. Resultant interventions have been suggested, yet the rate of recidivism remains high. Alexithymia, characterised by deficits in emotion processing and verbal expression, might interact with these other risk factors to affect outcomes.

AIM: Our goal was to examine the role of alexithymia as a possible moderator of risk factors for violent offender recidivism. Our hypothesis was that, albeit with other risk factors, alexithymia increases the risk of violent reoffending.

METHOD: We conducted a systematic literature review, using terms for alexithymia and violent offending and their intersection.

RESULTS: (a) No study that directly tests the role of alexithymia in conjunction with other potential risk factors for recidivism and actual violent recidivism was uncovered. (b) Primarily alexithymia researchers and primarily researchers into violence have separately found several clinical features in common between aspects of alexithymia and violence, such as impulsivity (total n = 24 studies). (c) Other researchers have established a relationship between alexithymia and both dynamic and static risk factors for violent recidivism (n = 16 studies).

CONCLUSION: Alexithymia may be a possible moderator of risk of violent offence recidivism. Supplementing offenders' rehabilitation efforts with assessments of alexithymia may assist in designing individually tailored interventions to promote desistance among violent offenders.}, } @article {pmid30914935, year = {2019}, author = {Tillman, R and Gordon, I and Naples, A and Rolison, M and Leckman, JF and Feldman, R and Pelphrey, KA and McPartland, JC}, title = {Oxytocin Enhances the Neural Efficiency of Social Perception.}, journal = {Frontiers in human neuroscience}, volume = {13}, number = {}, pages = {71}, pmid = {30914935}, issn = {1662-5161}, support = {K23 MH086785/MH/NIMH NIH HHS/United States ; R01 MH100173/MH/NIMH NIH HHS/United States ; R21 MH091309/MH/NIMH NIH HHS/United States ; }, abstract = {Face perception is a highly conserved process that directs our attention from infancy and is supported by specialized neural circuitry. Oxytocin (OT) can increase accuracy and detection of emotional faces, but these effects are mediated by valence, individual differences, and context. We investigated the temporal dynamics of OT's influence on the neural substrates of face perception using event related potentials (ERPs). In a double blind, placebo controlled within-subject design, 21 healthy male adults inhaled OT or placebo and underwent ERP imaging during two face processing tasks. Experiment 1 investigated effects of OT on neural correlates of fearful vs. neutral facial expressions, and Experiment 2 manipulated point-of-gaze to neutral faces. In Experiment 1, we found that OT reduced N170 latency to fearful faces. In Experiment 2, N170 latency was decreased when participant gaze was directed to the eyes of neutral faces; however, there were no OT-associated effects in response to different facial features. Findings suggest OT modulates early stages of social perception for socially complex information such as emotional faces relative to neutral. These results are consistent with models suggesting OT impacts the salience of socially informative cues during processing, which leads to downstream effects in behavior. Future work should examine how OT affects neural processes underlying basic components of social behavior (such as, face perception) while varying emotional expression of stimuli or comparing different characteristics of participants (e.g., gender, personality traits).}, } @article {pmid30914612, year = {2019}, author = {Oki, T and Sugimoto, T and Ogawa, M and Dabanaka, K and Hanazaki, K}, title = {[A Case of Early-Onset Breast Cancer for Which the Operative Indication for Breast Conservation Was Based on BRCA Genetic Testing].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {3}, pages = {555-557}, pmid = {30914612}, issn = {0385-0684}, mesh = {Adult ; *Breast Neoplasms/genetics/surgery ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Testing ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; *Neoplasm Recurrence, Local ; }, abstract = {We report a case of a patient with early-onset breast cancer who decided to undergo adaptation for breast-conserving surgery based on the results of genetic testing. A 25-year-old woman became aware of a lump in her left breast and visited a nearby hospital, where she was diagnosed with breast cancer. She has no personal history. Her paternal grandfather was diagnosed with rectal cancer at age 60. Ultrasonography revealed an irregularly-shaped hypoechoic mass measuring 3.8 cm in the C area of her left breast and an enlarged lymph node 2.0 cm in diameter in the left axillary area. The breast tumor was pathologically diagnosed as invasive ductal carcinoma by core needle biopsy and was immunohistochemically characterized as ER(-), PgR(-), and HER2(-), s o-called triple negative. Moreover, lymph node metastasis was confirmed by fine needle aspiration cytology. She underwent neoadjuvant chemotherapy and achieved a clinical complete response. A woman with early-onset triple negative breast cancer has a high probability of hereditary breast and ovarian cancer, with a high risk of ipsilateral second breast cancer after conserving surgery. Thus, BRCA genetic testing may be necessary before surgery. As no pathogenic mutation wasfound in BRCA 1/2 in this case, the patient underwent breast-conserving surgery followed by radiation therapy for the conserved breast. The patient remained healthy and without any recurrence 4 years and 2 months after surgery.}, } @article {pmid30914564, year = {2019}, author = {Takizawa, K and Sakata, J and Ando, T and Yuza, K and Toge, K and Hirose, Y and Nakano, T and Ishikawa, H and Katada, T and Miura, K and Nagahashi, M and Shimada, Y and Kameyama, H and Kobayashi, T and Wakai, T}, title = {[A Case of Peritoneal Recurrence of Invasive Ductal Carcinoma Derived from Intraductal Papillary Mucinous Neoplasm after Surgery Treated with Palliative Radiation Therapy and Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {372-374}, pmid = {30914564}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Mucinous ; Aged, 80 and over ; *Carcinoma, Pancreatic Ductal/pathology/therapy ; Combined Modality Therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology/therapy ; *Peritoneal Neoplasms/secondary/therapy ; }, abstract = {An 82-year-old man with a diagnosis ofintraductal papillary mucinous carcinoma(IPMC)underwent pancreaticoduodenectomy followed by adjuvant chemotherapy with S-1. Six months after surgery, he had upper abdominal pain, and CT demonstrated a recurrent intraabdominal tumor located at the surgical incision scar. It was diagnosed as a solitary peritoneal recurrence, and palliative radiation therapy at a dose of 30 Gy was performed for the relief of abdominal pain after administration ofoxycodone. He was free ofpain without pharmacological therapy and received subsequent chemotherapy with nabpaclitaxel plus gemcitabine(GnP). He remains free ofpain and alive without progression ofthe disease 24 months after recurrence. Hypofractionated-accelerated radiotherapy is feasible and results in pain relief for local recurrence of IPMC.}, } @article {pmid30914557, year = {2019}, author = {Koyama, Y and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[A Case of Synchronous Bilateral Breast Cancer in an Elderly Patient].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {351-353}, pmid = {30914557}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/diagnosis/surgery ; Female ; Humans ; Lymphatic Metastasis ; Mammography ; Mastectomy ; *Neoplasms, Second Primary/diagnosis/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {We encountered a case of synchronous bilateral breast cancer in an elderly patient. A 75-year-old woman visited our hospital because she was identified with an abnormality on mammography during breast cancer screening. An elastic hard tumor 2.0 cm in diameter was detected in the A area of her right breast. Mammography showed an irregular tumor shadow with spicula in the right breast and micro-calcifications in her left breast. Ultrasonography showed a low echoic lesion 20mm in size in the A area of her right breast and a low echoic area 5mm in size in her left breast. Histological examination of core needle biopsy specimens revealed invasive ductal carcinoma in both breasts. Synchronous bilateral breast cancer was diagnosed. Bilateral muscle-preserving mastectomy with sentinel lymph node biopsy was performed. Postoperative histology revealed bilateral invasive ductal carcinoma without lymph node metastasis that was positive for ER and PgR, was negative for HER2, and had a Ki-67-positive cell index of 20% in the right breast(T1N0M0, Stage Ⅰ), and that was positive for ER, was negative for PgR and HER2, and had a Ki-67-positive cell index of 5% in the left breast(T1N0M0, Stage Ⅰ). The surgical margins were negative. She was administered endocrine therapy as adjuvant therapy for 5 years after the surgery. Eight years after the surgery, she was well without metastasis.}, } @article {pmid30914556, year = {2019}, author = {Hirano, T and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[The Diagnostic Problem of the Automated Breast Volume Scanner(ABUS) for Paget Disease-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {348-350}, pmid = {30914556}, issn = {0385-0684}, mesh = {Adult ; Automation ; *Breast Neoplasms/diagnostic imaging/surgery ; Female ; Humans ; *Mammography ; *Mastectomy ; Neoplasm Recurrence, Local ; Sentinel Lymph Node Biopsy ; }, abstract = {The patient, a 41-year-old woman, presented with an elastic soft tumor on her left breast. Sore skin was observed on the left nipple and areola. Mammography revealed poor extension at the left nipple surrounding skin. A hand-held ultrasonography(HHUS)device and automated breast volume scanner(ABUS)did not detect the thickening of the skin. Surgical biopsy was performed. The skin lesion was diagnosed as Paget disease. We examined her whole body and made a diagnosis of Tis N0 M0, stage 0. The patient underwent a mastectomy and sentinel lymph node biopsy. The pathological diagnosis on the basis of the resected surgical specimen was invasive ductal carcinoma, negative for ER and PgR, and positive for HER2/neu protein expression, and the Ki-67-positive cell index was 30%. The surgical margins were negative, and no metastasis was found in the sentinel lymph node. She was given trastuzumab as adjuvant therapy. Two years after the surgery, she was well without recurrence.}, } @article {pmid30914555, year = {2019}, author = {Monden, K and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[The Diagnostic Problem of Automated Breast Volume Scanner(ABUS)for a Breast Cancer Patient with Dementia-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {345-347}, pmid = {30914555}, issn = {0385-0684}, mesh = {Aged, 80 and over ; *Breast Neoplasms/complications/diagnosis ; *Dementia/complications ; Female ; Humans ; Mammography ; Mastectomy ; *Sentinel Lymph Node Biopsy ; }, abstract = {The patient was an 84-year-old woman.She had presented with a mass on her right breast.Mammography revealed an illdefined mass.Handheld ultrasonography(HHUS)revealed a low echoic mass, 25mm in diameter, on the AC area of her right breast.An automated breast volume scanner(ABUS)was not useful for detecting the lesion because the patient had dementia and restless body movements.A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma, which was positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.We examined her whole body and made a diagnosis of T2N0M0, StageⅡA.She underwent a muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma, positive for estrogen and progesterone receptors, and negative for HER2/neu.The Ki-67-positive cell index was 70%.The surgical margins were negative for malignancy, and no metastasis was observed in the sentinel lymph node.She was given endocrine as adjuvant therapies.Three years after the surgery, she was well without metastases.Patients with dementia could not use ABUS.HHUS will be useful for these patients.}, } @article {pmid30914551, year = {2019}, author = {Mori, S and Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Tomita, R}, title = {[A Case of Sentinel Lymph Node Biopsy for Breast Cancer in an Elderly Man].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {333-335}, pmid = {30914551}, issn = {0385-0684}, mesh = {Aged ; Biopsy, Large-Core Needle ; *Breast Neoplasms, Male/diagnosis ; Humans ; Male ; Mammography ; Mastectomy ; *Sentinel Lymph Node Biopsy ; }, abstract = {A 75-year-old man noted an elastic hard tumor under his left areola.Mammography showed a microlobulated mass, so he was diagnosed with category Ⅳ breast cancer.Ultrasonography showed a circular hypo-echoic mass that was 21mm in diameter with a moderately indistinct border.Based on core needle biopsy, the tumor was diagnosed as invasive ductal carcinoma.We performed a whole-body check-up, and he was diagnosed with T1N0M0, StageⅠ breast cancer.The patient underwent mastectomy and sentinel lymph node biopsy.The pathological diagnosis based on the resected surgical specimen was invasive ductal carcinoma, positive for ER and negative for PgR and HER2/neu protein expression, and the Ki-67 positive cell index was 20%.The surgical margins were negative, and there was no metastasis in the sentinel lymph nodes.He was administered endocrine therapy as adjuvant therapy.Two years after the surgery, he remains well without metastases.}, } @article {pmid30914543, year = {2019}, author = {Adachi, K and Sakurai, K and Kubota, H and Suzuki, Y and Suzuki, S and Makishima, M and Koshinaga, T}, title = {[Treatment for Breast Cancer in an Elderly Male Patient-Report of a Case].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {46}, number = {2}, pages = {309-311}, pmid = {30914543}, issn = {0385-0684}, mesh = {Aged ; Biopsy, Large-Core Needle ; *Breast Neoplasms/diagnosis/therapy ; Humans ; Lymphatic Metastasis ; Male ; Mammography ; Mastectomy ; }, abstract = {Breast cancer in male is comparatively rare. We encountered a case of breast cancer in an elderly male who was treated with consideration of age. A 78-year-old male consulted our hospital with a lump on his right breast. The tumor was 3 cm in diameter and was palpable in the E area of his right breast, accompanied by pain. Mammography showed an indistinct mass in the S area. Ultrasonography revealed a well-defined and rough, lobulated mass. Core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. Metastatic work-up revealed no evidence of metastasis. The patient underwent mastectomy with sentinel lymph node(SN)biopsy and axial lymph node dissection(Ax)because of positive metastasis in an SN. The pathological findings from the surgically resected specimens indicated solid-tubular carcinoma. Lymph node metastases were observed in an SN(1/1)and Ax(1/3). On immunohistochemistry, tumor cells tested positive for estrogen and progesterone receptors and negative for HER2/neu protein expression. The Ki-67 labeling index was 14%. Postoperatively, the patient has not received chemotherapy, but received hormone therapy as adjuvant therapy considering his age. Nine months after the surgery, the patient is well, and metastasis has not appeared.}, } @article {pmid30914287, year = {2019}, author = {Arslan, E and Çermik, TF and Didem Can Trabulus, F and Canan Kelten Talu, E and Başaran, Ş}, title = {Diagnostic impact of [18]F-FDG PET/CT on the management of rare breast carcinomas: Apocrine and neuroendocrine carcinomas.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {38}, number = {3}, pages = {147-153}, doi = {10.1016/j.remn.2018.11.007}, pmid = {30914287}, issn = {2253-8089}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Neuroendocrine/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; *Positron Emission Tomography Computed Tomography/methods ; *Radiopharmaceuticals ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: We aimed to evaluate the diagnostic impact of [18]F-FDG PET/CT in staging apocrine breast carcinoma (ABC) and primary breast neuroendocrine carcinoma (PBNEC) and to demonstrate possible alterations of the [18]F-FDG uptake in these histopathologic subtypes. In addition, we aimed to compare [18]F-FDG PET/CT findings between ABC, PBNEC and invasive ductal carcinoma.

MATERIAL AND METHODS: A total of 570 patients and 585 breast lesions were retrospectively included in this study. After patients were classified into molecular subtypes according to the histopathological analysis, [18]F-FDG PET/CT imaging was performed. The SUVmax findings of primary tumors obtained from [18]F-FDG PET/CT were compared between the groups.

RESULTS: Invasive ductal carcinoma was the most prevalent breast carcinoma (77.7%, n=446), with a low proportion of ABC (4.1%, n=24) and PBNEC (2.4%; n=14) diagnosed. The highest mean SUVmax was calculated in HER2 subtype of ABC and [18]F-FDG uptake ratio in HER2 and TN subtypes were found statistically higher than Luminal B type of ABC (p=0.038 and p=0.019, respectively). Although [18]F-FDG uptake in Luminal B subtype of PBNEC was higher than Luminal A subtype, difference was not statistically significant. Additionally, the axillary metastasis rate was significantly higher in the ABC group (p=0.015).

CONCLUSIONS: The histopathological ABC subtype group showed different [18]F-FDG uptake than the invasive ductal carcinoma group. Even if [18]F-FDG uptake was lower in the PBNEC group than in the other groups, PET/CT showed and adequate performance in detecting primary tumors and metastases. The [18]F-FDG PET/CT scan results may contribute to the initial staging and management of ABC and PBNEC patients.}, } @article {pmid30913871, year = {2019}, author = {Chen, WR and Deng, JP and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases.}, journal = {Cancer research and treatment}, volume = {51}, number = {4}, pages = {1437-1448}, pmid = {30913871}, issn = {2005-9256}, support = {81872459//National Natural Science Foundation of China/ ; 81803050//National Natural Science Foundation of China/ ; 2016J01635//Natural Science Foundation of Fujian Province/ ; 2018A030313666//Guangdong Academy of Sciences/ ; }, mesh = {Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant ; Clinical Decision-Making/*methods ; Female ; Gene Expression Profiling/methods ; Humans ; Multivariate Analysis ; Neoplasm Micrometastasis/drug therapy/*genetics ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; SEER Program ; Treatment Outcome ; }, abstract = {PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed.

RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs.

CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.}, } @article {pmid30912402, year = {2019}, author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Zargar, MA}, title = {Association of Protein Expression and Methylation of DAPK1 with Clinicopathological Features in Invasive Ductal Carcinoma Patients from Kashmir.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {3}, pages = {839-848}, pmid = {30912402}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *DNA Methylation ; Death-Associated Protein Kinases/*genetics/*metabolism ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; }, abstract = {Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer.}, } @article {pmid30909807, year = {2020}, author = {Ein-Dor, T and Hirschberger, G and Tsur, N and Mikulincer, M and Bazak, SB and Solomon, Z}, title = {The link between attachment orientations and cellular aging among former prisoners of war.}, journal = {Attachment & human development}, volume = {22}, number = {3}, pages = {352-366}, doi = {10.1080/14616734.2019.1589545}, pmid = {30909807}, issn = {1469-2988}, mesh = {Aged ; Anxiety/epidemiology/*physiopathology/psychology ; Cellular Senescence/*physiology ; Female ; Humans ; Israel/epidemiology ; Longitudinal Studies ; Male ; Middle Aged ; *Object Attachment ; Prisoners of War/*psychology ; Prospective Studies ; Psychological Trauma/epidemiology/*physiopathology/psychology ; Socioeconomic Factors ; Spouses/psychology ; Telomere/metabolism ; }, abstract = {Objective: Ex-prisoners of war (ex-POWs) experience prolonged distress that in some cases may influence their cellular aging (telomere length). The current research examines whether attachment orientations of ex-POWs and their spouses can explain individual differences in telomere length 40 years after the experience of captivity.Methods: Eighty-eight Israeli ex-POWs were assessed at four time points since captivity, whereas their spouses at three time points. Attachment orientations (anxiety, avoidance) were assessed in three time points and telomere length was measured at time four.Results: Findings indicated that ex-POWs' attachment avoidance was associated with shorter telomere length. In addition, spouses' attachment anxiety was associated with shorter telomere length among ex-POWs, whereas spouses' attachment avoidance was unexpectedly related to longer telomere length among ex-POWs.Conclusions: Results suggest that the effects of trauma on cellular aging are not uniform and that intrapersonal and interpersonal variables may moderate responses to trauma at the cellular level.}, } @article {pmid30907288, year = {2019}, author = {Efrati, Y and Gerber, Z and Tolmacz, R}, title = {The Relation of Intra-Psychic and Relational Aspects of the Self to Compulsive Sexual Behavior.}, journal = {Journal of sex & marital therapy}, volume = {45}, number = {7}, pages = {618-631}, doi = {10.1080/0092623X.2019.1599092}, pmid = {30907288}, issn = {1521-0715}, mesh = {Adult ; Behavior, Addictive/*psychology ; Case-Control Studies ; Compulsive Behavior/*psychology ; Erotica/*psychology ; Female ; Humans ; Israel ; Male ; Narcissism ; Self Report ; Sexual Behavior/psychology ; Sexual Dysfunctions, Psychological/*psychology ; Surveys and Questionnaires ; Unsafe Sex/psychology ; Young Adult ; }, abstract = {Background and Aims: Research has indicated that addictions include not only the consumption of psychoactive substances but also behavioral addictions such as compulsive sexual behavior (CSB). In the current study we examine differences in the "addictive personality" of people with CSB as well as drug addicts. Methods: The sample sized included 160 Israeli men, of whom 67 were members of Sexaholics Anonymous (SA) support groups, 48 were members of Narcotics Anonymous (NA) support groups, and 45 were from the general community. Self-report measures of intra-psychic (narcissism, self-compassion, self-efficacy) and relational-related (sense of entitlement, pathological concern) measures were administrated. Results: Results indicate that SA groups had higher narcissism, lacked self-compassion and efficacy, and had greater pathological senses of entitlement and concern than drug addicts and control individuals. Conclusion: A theoretical conceptualization of these results is presented as a basis for future research directions and clinical intervention.}, } @article {pmid30905927, year = {2019}, author = {Koc-Günel, S and Tekeli, N and Smaczny, C and Vogl, T and Rohde, G}, title = {A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {390-393}, pmid = {30905927}, issn = {1941-5923}, mesh = {Breast Neoplasms/*complications ; Female ; Humans ; Lung Neoplasms/*complications/*diagnosis ; Lymphangioleiomyomatosis/*complications/*diagnosis ; Middle Aged ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. CASE REPORT A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. CONCLUSIONS A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.}, } @article {pmid30903273, year = {2019}, author = {Chiu, K and Ionescu, DN and Hayes, M}, title = {SOX10 expression in mammary invasive ductal carcinomas and benign breast tissue.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {474}, number = {6}, pages = {667-672}, pmid = {30903273}, issn = {1432-2307}, mesh = {Biomarkers, Tumor/analysis/metabolism ; Breast/*pathology ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Epithelial Cells/pathology ; Humans ; Immunohistochemistry ; Melanoma/pathology ; SOXE Transcription Factors/*metabolism ; }, abstract = {SOX10 immunohistochemistry is used to identify tumors of neural crest origin, including melanocytic neoplasms. SOX10 expression has also been identified in myoepithelial cells of the breast and in a subset of invasive mammary carcinomas. In order to characterize SOX10 expression in ductal carcinomas of the breast, the aim of this study was to characterize the SOX10 in invasive ductal carcinomas according to molecular subtype, DCIS, and benign breast tissue. Forty cases of invasive ductal carcinoma of the breast were retrieved, with ten cases with immunohistochemical profile compatible with luminal A-like, luminal B-HER2-positive, non-luminal HER2-positive, and triple-negative subtypes. Whole tissue sections from each case were stained with SOX10. Six (60%) of ten triple-negative tumors were SOX10+ compared with 1 (3%) of 30 carcinomas of other molecular subtypes. All but one of the positive tumors showed at least moderate expression in at least 40% of tumor cells. All seven cases SOX10+ carcinomas were grade 3 tumors. Of the 13 cases with DCIS available for assessment, one (8%) showed positive SOX10 expression (a case associated with triple-negative carcinoma). Twenty-two cases contained normal breast tissue that showed SOX10 expression in both myoepithelial and luminal cells, predominantly patchy with variable intensity. SOX10 showed incomplete myoepithelial staining compared to other myoepithelial markers. In conclusion, SOX10 IHC cannot reliably differentiate between high-grade triple-negative carcinomas, melanomas, and myoepithelial tumors in the breast. SOX10 is not as robust a myoepithelial marker compared with other established markers.}, } @article {pmid30900303, year = {2019}, author = {Nie, L and Pan, X and Zhang, M and Yin, X and Gong, J and Chen, X and Xu, M and Zhou, Q and Chen, N}, title = {The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center.}, journal = {The Prostate}, volume = {79}, number = {8}, pages = {819-825}, doi = {10.1002/pros.23785}, pmid = {30900303}, issn = {1097-0045}, mesh = {Biopsy, Large-Core Needle/methods ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cohort Studies ; Gene Expression ; Gene Rearrangement ; Genetic Heterogeneity ; Humans ; Image-Guided Biopsy/methods ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostatic Neoplasms/genetics/*metabolism/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism/pathology ; Serine Endopeptidases/genetics/metabolism ; Transcriptional Regulator ERG/biosynthesis/genetics ; Tumor Burden ; }, abstract = {BACKGROUND: Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial.

METHOD: In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core-needle biopsy in the West China Hospital.

RESULT: Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P = 0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P = 0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P = 0.012). Follow-up analysis found that patients who progressed to castration-resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)-sensitive cases (14.1% vs 23.5%, P = 0.042), but Kaplan-Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG-positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases, ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG-positive cells were identified neither by IHC nor FISH.

CONCLUSION: This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC-P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT.}, } @article {pmid30897929, year = {2019}, author = {Yoon, GY and Cha, JH and Kim, HH and Shin, HJ and Chae, EY and Choi, WJ}, title = {Comparison of invasive micropapillary and invasive ductal carcinoma of the breast: a matched cohort study.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {60}, number = {11}, pages = {1405-1413}, doi = {10.1177/0284185119834689}, pmid = {30897929}, issn = {1600-0455}, mesh = {Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/therapy ; Cohort Studies ; Diagnosis, Differential ; Female ; Humans ; *Mammography ; Middle Aged ; Retrospective Studies ; Survival Analysis ; }, } @article {pmid30897334, year = {2019}, author = {Wang, YF and Han, J}, title = {OTOR in breast carcinoma as a potent prognostic predictor correlates with cell proliferation, migration, and invasiveness.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {97}, number = {6}, pages = {750-757}, doi = {10.1139/bcb-2018-0305}, pmid = {30897334}, issn = {1208-6002}, mesh = {Biomarkers, Tumor/antagonists & inhibitors/*genetics/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/*pathology ; *Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Prognosis ; Proteins/antagonists & inhibitors/*genetics/metabolism ; RNA, Small Interfering/pharmacology ; }, abstract = {Otoraplin (OTOR), recognized as an important cochlear gene, has a predicted secretory signal peptide sequence and harbors a high degree of cross-species conservation. However, its role in tumor progression is relatively unclear, especially in breast carcinoma (BC). This study investigated the clinicopathological significance of OTOR in breast infiltrating ductal carcinoma (IDC) with high metastasis to uncover its biological function in BC. OTOR was highly overexpressed in BC tissues and cells compared with normal samples. OTOR overexpression was associated with certain clinicopathological characteristics and poorer prognosis (overall survival; OS) of patients with breast IDC. As determined using CCK-8, colony formation, wound-healing, and Transwell assays, silencing OTOR using siRNA impeded BC-cell proliferation, migration, and invasiveness, which may have resulted from inactivating the mitogen-activated protein kinase - extracellular-signal-regulated kinase pathway. These results indicate that OTOR plays a crucial role in the progression of and prognosis for BC, which could help to identify future therapeutic targets for treating BC patients.}, } @article {pmid30890538, year = {2019}, author = {Rohm, M and Zeigerer, A and Machado, J and Herzig, S}, title = {Energy metabolism in cachexia.}, journal = {EMBO reports}, volume = {20}, number = {4}, pages = {}, pmid = {30890538}, issn = {1469-3178}, mesh = {Adipose Tissue/metabolism ; Animals ; Cachexia/etiology/*metabolism ; *Energy Metabolism ; Gastrointestinal Absorption ; Humans ; Liver/metabolism ; Muscle, Skeletal/metabolism ; Neoplasms/complications/metabolism ; Organ Specificity ; }, abstract = {Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.}, } @article {pmid30890151, year = {2019}, author = {Tewari, SG and Rajaram, K and Schyman, P and Swift, R and Reifman, J and Prigge, ST and Wallqvist, A}, title = {Short-term metabolic adjustments in Plasmodium falciparum counter hypoxanthine deprivation at the expense of long-term viability.}, journal = {Malaria journal}, volume = {18}, number = {1}, pages = {86}, pmid = {30890151}, issn = {1475-2875}, support = {R01 AI125534/AI/NIAID NIH HHS/United States ; AI125534//National Institute of Allergy and Infectious Diseases/ ; W81XWH-15-C-0061//Medical Research and Materiel Command/ ; }, mesh = {*Adaptation, Physiological ; Animals ; Gene Expression Profiling ; Hypoxanthine/*metabolism ; Metabolic Networks and Pathways ; Metabolomics ; Plasmodium falciparum/growth & development/metabolism/*physiology ; Survival ; Time Factors ; }, abstract = {BACKGROUND: The malarial parasite Plasmodium falciparum is an auxotroph for purines, which are required for nucleic acid synthesis during the intra-erythrocytic developmental cycle (IDC) of the parasite. The capabilities of the parasite and extent to which it can use compensatory mechanisms to adapt to purine deprivation were studied by examining changes in its metabolism under sub-optimal concentrations of hypoxanthine, the primary precursor utilized by the parasite for purine-based nucleic acid synthesis.

METHODS: The concentration of hypoxanthine that caused a moderate growth defect over the course of one IDC was determined. At this concentration of hypoxanthine (0.5 μM), transcriptomic and metabolomic data were collected during one IDC at multiple time points. These data were integrated with a metabolic network model of the parasite embedded in a red blood cell (RBC) to interpret the metabolic adaptation of P. falciparum to hypoxanthine deprivation.

RESULTS: At a hypoxanthine concentration of 0.5 μM, vacuole-like structures in the cytosol of many P. falciparum parasites were observed after the 24-h midpoint of the IDC. Parasites grown under these conditions experienced a slowdown in the progression of the IDC. After 72 h of deprivation, the parasite growth could not be recovered despite supplementation with 90 µM hypoxanthine. Simulations of P. falciparum metabolism suggested that alterations in ubiquinone, isoprenoid, shikimate, and mitochondrial metabolism occurred before the appearance of these vacuole-like structures. Alterations were found in metabolic reactions associated with fatty acid synthesis, the pentose phosphate pathway, methionine metabolism, and coenzyme A synthesis in the latter half of the IDC. Furthermore, gene set enrichment analysis revealed that P. falciparum activated genes associated with rosette formation, Maurer's cleft and protein export under two different nutrient-deprivation conditions (hypoxanthine and isoleucine).

CONCLUSIONS: The metabolic network analysis presented here suggests that P. falciparum invokes specific purine-recycling pathways to compensate for hypoxanthine deprivation and maintains a hypoxanthine pool for purine-based nucleic acid synthesis. However, this compensatory mechanism is not sufficient to maintain long-term viability of the parasite. Although P. falciparum can complete a full IDC in low hypoxanthine conditions, subsequent cycles are disrupted.}, } @article {pmid30888194, year = {2019}, author = {Yang, M and Xu, Z and Zhang, QZ and Wang, K and Ji, XY and Xu, J and Zhang, JY and Niu, G}, title = {A breast one-patient panel of heterogeneous genomes reveals genetic alterations driving DCIS into invasive lesions.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1565-1576}, doi = {10.2217/fon-2018-0555}, pmid = {30888194}, issn = {1744-8301}, mesh = {Actinin/genetics ; Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/metabolism/mortality ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism ; DNA Copy Number Variations ; Female ; *Genetic Heterogeneity ; *Genetic Variation ; *Genomics/methods ; Humans ; Mammography/methods ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Precision Medicine ; Prognosis ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; Exome Sequencing ; }, abstract = {Aim: Utilize breast cancer samples in the same patient to indicate breast cancer development. Patients & methods: We performed whole-exome analysis of spatially independent ductal carcinoma in situ (DCIS) and invasive ductal carcinoma samples from the same breast. Results: In VEGF pathway, we observed two genes disrupted in DCIS, while another four (including ACTN2) mutated in invasive ductal carcinoma. When looked up TCGA database, we identified seven breast cancer patients with ACTN2 somatic mutations and observed a dramatic decrease in the overall survival time in ACTN2 mutant patients (p = 0.0182). A further finding in the TCGA database shows that breast cancer patients with ≥2 mutated genes in VEGF pathways showed worse prognosis (p = 0.0013). Conclusion: TCGA database and special case could inform each other to reveal DCIS developmental rules.}, } @article {pmid30887570, year = {2019}, author = {Kashefi, S and Omranipour, R and Mahmoodzadeh, H and Ahmadi, H and Alikhassi, A and Hosseini, M and Cuzzocrea, S and Rehm, BHA and Matsuo, H and Mirshafiey, A}, title = {A randomized, controlled, phase II clinical trial of β-D-mannuronic acid (M2000) in pre-surgical breast cancer patients at early stage (T1-T2).}, journal = {Clinical and experimental pharmacology & physiology}, volume = {46}, number = {6}, pages = {527-532}, doi = {10.1111/1440-1681.13086}, pmid = {30887570}, issn = {1440-1681}, mesh = {Breast Neoplasms/*drug therapy/*pathology/surgery ; Female ; Hexuronic Acids/adverse effects/*therapeutic use ; Humans ; Middle Aged ; Neoplasm Staging ; Safety ; }, abstract = {Following the potent efficacy of β-D-Mannuronic acid in a breast cancer murine model, we evaluated the efficacy of this novel non-steroidal anti-inflammatory drug in breast cancer patients in the present clinical trial. The study was an 8-week randomized, controlled, phase II clinical trial (IRCT: 2017012213739N7 (in 48 pre-surgical breast cancer patients. Patients who had breast cancer at early stage, with invasive ductal carcinoma, were placed on a waiting-list for surgery and were allocated to the study. β-D-Mannuronic was administrated at a dose of two capsules (1000 mg/d) orally during a period of 8 weeks. The end point of this study was when the patients were admitted for surgery. Moreover, the patients' well-being status was followed up on for safety. There were no statistically significant differences between treatment and non-treatment groups at baseline. β-D-Mannuronic acid therapy, from 20 patients, showed that in one patient (5%) tumour size was decreased; in five patients (25%) tumour growth was stopped; and in 14 patients (70%) the growth rate in the treatment group did not show significant change, compared to the non-treatment group. Evaluation of two tumour markers (carcinoembryonic antigen and cancer antigen 15-3) showed that there was no significant difference between before and after treatment. Although the use of some non-steroidal anti-inflammatory drugs in a long time period has shown a prophylactic effect in breast cancer, their therapeutic efficacy in a short time period is unknown, whereas treatment with β-D-Mannuronic acid during 8 weeks could show 30% therapeutic effects in pre-surgical breast cancer patients.}, } @article {pmid30885157, year = {2019}, author = {Patel, C and Hürlimann, E and Keller, L and Hattendorf, J and Sayasone, S and Ali, SM and Ame, SM and Coulibaly, JT and Keiser, J}, title = {Efficacy and safety of ivermectin and albendazole co-administration in school-aged children and adults infected with Trichuris trichiura: study protocol for a multi-country randomized controlled double-blind trial.}, journal = {BMC infectious diseases}, volume = {19}, number = {1}, pages = {262}, pmid = {30885157}, issn = {1471-2334}, support = {OPP1153928//Bill and Melinda Gates Foundation/ ; }, mesh = {Adolescent ; Adult ; Albendazole/*therapeutic use ; Animals ; Anthelmintics/*therapeutic use ; Child ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Ivermectin/*therapeutic use ; Logistic Models ; Male ; Middle Aged ; Trichuriasis/*drug therapy ; *Trichuris ; Young Adult ; }, abstract = {BACKGROUND: Soil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis.

METHODS: A double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d'Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6-60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14-21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14-21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight.

DISCUSSION: This trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity.

TRIAL REGISTRATION: NCT03527732 (date assigned: 17 May 2018).}, } @article {pmid30879795, year = {2019}, author = {Sheaffer, WW and Gray, RJ and Wasif, N and Stucky, CC and Cronin, PA and Kosiorek, HE and Basu, A and Pizzitola, VJ and Patel, B and Giurescu, ME and Lorans, R and McCullough, AE and Ocal, IT and Pockaj, BA}, title = {Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy.}, journal = {American journal of surgery}, volume = {217}, number = {6}, pages = {1025-1029}, doi = {10.1016/j.amjsurg.2018.12.069}, pmid = {30879795}, issn = {1879-1883}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology/surgery ; Female ; Humans ; *Mastectomy, Radical ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Upstaging from DCIS to invasive ductal carcinoma varies widely from 0 to 59%. We aim to identify risk factors associated with upstaging in all DCIS patients and based on specific surgical intervention.

METHODS: Patients with a pre-operative diagnosis of DCIS undergoing BCT or mastectomy were reviewed. Multivariable analysis was performed to identify risk factors for upstaging.

RESULTS: In total, 623 patients had a preoperative diagnosis of DCIS. Upstaging occurred in 74 patients (12%) overall. There was no difference in upstaging rates between mastectomy and BCT (11% v 14% p = 0.27). Sentinel lymph node biopsy was positive in 4/212 patients (1%). Multivariable analysis revealed suspicion of microinvasion (OR 5.7 95%CI2.2-14.9), surgeon suspicion of invasive disease (OR 2.7, 95% CI 1.2-6.4) and larger size/multicentric/extensive tumor (OR 1.9 95% CI 1.1-3.4) increase risk of upstaging.

CONCLUSIONS: Suspicion of microinvasion, surgeon suspicion, and tumor size can be used to help guide the use of sentinel lymph node biopsy. For patients without these high risk characteristics, it is hard to justify the use of concurrent SLN biopsy for patients who undergo BCT.}, } @article {pmid30873970, year = {2019}, author = {Butola, A and Ahmad, A and Dubey, V and Srivastava, V and Qaiser, D and Srivastava, A and Senthilkumaran, P and Mehta, DS}, title = {Volumetric analysis of breast cancer tissues using machine learning and swept-source optical coherence tomography.}, journal = {Applied optics}, volume = {58}, number = {5}, pages = {A135-A141}, doi = {10.1364/AO.58.00A135}, pmid = {30873970}, issn = {1539-4522}, mesh = {Algorithms ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; *Machine Learning ; Reproducibility of Results ; Support Vector Machine ; Tomography, Optical Coherence/*methods ; }, abstract = {In breast cancer, 20%-30% of cases require a second surgery because of incomplete excision of malignant tissues. Therefore, to avoid the risk of recurrence, accurate detection of the cancer margin by the clinician or surgeons needs some assistance. In this paper, an automated volumetric analysis of normal and breast cancer tissue is done by a machine learning algorithm to separate them into two classes. The proposed method is based on a support-vector-machine-based classifier by dissociating 10 features extracted from the A-line, texture, and phase map by the swept-source optical coherence tomographic intensity and phase images. A set of 88 freshly excised breast tissue [44 normal and 44 cancers (invasive ductal carcinoma tissues)] samples from 22 patients was used in our study. The algorithm successfully classifies the cancerous tissue with sensitivity, specificity, and accuracy of 91.56%, 93.86%, and 92.71% respectively. The present computational technique is fast, simple, and sensitive, and extracts features from the whole volume of the tissue, which does not require any special tissue preparation nor an expert to analyze the breast cancer as required in histopathology. Diagnosis of breast cancer by extracting quantitative features from optical coherence tomographic images could be a potentially powerful method for cancer detection and would be a valuable tool for a fine-needle-guided biopsy.}, } @article {pmid30872758, year = {2019}, author = {Roth, JD and Pariser, JJ and Stoffel, JT and Lenherr, SM and Myers, JB and Welk, B and Elliott, SP}, title = {Patient subjective assessment of urinary tract infection frequency and severity is associated with bladder management method in spinal cord injury.}, journal = {Spinal cord}, volume = {57}, number = {8}, pages = {700-707}, pmid = {30872758}, issn = {1476-5624}, support = {CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; CER14092138//Patient-Centered Outcomes Research Institute (PCORI)/ ; }, mesh = {Adult ; Catheters, Indwelling/adverse effects/*trends ; Cross-Sectional Studies ; *Diagnostic Self Evaluation ; Female ; Humans ; Intermittent Urethral Catheterization/adverse effects/*trends ; Male ; Middle Aged ; Prospective Studies ; Registries ; Severity of Illness Index ; Spinal Cord Injuries/*complications/diagnosis/*therapy ; Urinary Tract Infections/diagnosis/*etiology ; }, abstract = {STUDY DESIGN: The Neurogenic Bladder Research Group (NBRG) registry is a multicenter prospective observational study. This manuscript is retrospective based on a cross-sectional survey.

OBJECTIVES: To assess patient subjective assessment of urinary tract infection (UTI) frequency and severity are associated with the degree of use of catheters or incontinence products.

SETTING: Multiple hospitals across the United States.

METHODS: Eligibility included: age > 18 years and acquired SCI. Over 1.5 years, 1479 eligible participants were enrolled. We excluded those with surgical reconstruction or diversion of the bladder. In total, 1282 participants were grouped by bladder management: (1) indwelling catheter (IDC), (2) clean intermittent catheterization (CIC), (3) external devices (pads/condom), and (4) volitional voiding (Void). UTI frequency was classified as 0, 1-3, 4-6, or > 6 over the prior year. UTI severity was determined by hospitalization for UTI in the prior year. Multivariate regression compared these factors across groups.

RESULTS: UTIs were least frequent in Void followed by pads/condom, CIC, and IDC (all p ≤ 0.001). UTI severity followed a similar pattern. Controlling for covariates, the adjusted odds of UTI frequency (Void = reference) were 2.28 (1.38-3.76) for pads/condom, 3.42 (2.25-5.18) for CIC, and 4.3 (2.59-6.70) for IDC (all p ≤ 0.001).

CONCLUSIONS: Patient subjective assessment of UTI frequency is highest with IDC, followed by CIC, pads/condom, and lowest with spontaneous voiding. The odds of hospitalization for UTI were three times higher for IDC than spontaneous voiding. UTI risk should be considered when counseling patients about bladder management options. These associations do not imply causation but warrant further investigation in a prospective manner.

SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) Award (CER14092138).}, } @article {pmid30872384, year = {2019}, author = {Li, Y and Zhang, N and Zhang, H and Yang, Q}, title = {Comparative prognostic analysis for triple-negative breast cancer with metaplastic and invasive ductal carcinoma.}, journal = {Journal of clinical pathology}, volume = {72}, number = {6}, pages = {418-424}, doi = {10.1136/jclinpath-2018-205544}, pmid = {30872384}, issn = {1472-4146}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/ethnology/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Invasiveness ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/ethnology/mortality/*pathology/therapy ; United States/epidemiology ; Young Adult ; }, abstract = {AIMS: Triple-negative breast cancer comprises different histological subtypes, including metaplastic breast cancer (MBC) and ductal carcinomas (IDCs). The purpose of this study was to compare triple-negative MBC (TN-MBC) with triple-negative IDC (TN-IDC) in terms of survival and predictive factors.

METHODS: With access to the Surveillance, Epidemiology and End Result (SEER) database, a total of 19 383 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using the χ[2] test. Univariate and multivariate analyses were applied to evaluate the disease-specific survival (DSS) and overall survival (OS). Subgroup analyses summarised the hazard ratios of TN-MBC versus TN-IDC using a forest plot.

RESULTS: A total of 586 patients with TN-MBC and 18 797 with TN-IDC were included in this study. Patients with TN-MBC were older and presented with larger tumour sizes, relatively rare lymph node positive disease, and had received more chemotherapy. Compared with TN-IDC, the TN-MBC group showed a significantly poorer prognosis before and after the 1:3 matched case-control analysis. Further subgroup analysis indicated that patients with TN-MBC were older, were from specific races, and those with distant metastasis and not receiving radiotherapy had worse prognosis than patients with TN-IDC in terms of DFS and OS.

CONCLUSION: Our results showed that patients with TN-MBC had unique clinicopathological characteristics and poorer prognostic subtype compared with TN-IDC. This improves our understanding of the clinicopathological and prognostic features of this rare entity but also provides more convincing therapeutic guidelines for TN-MBC in patients with breast cancer.}, } @article {pmid30870012, year = {2019}, author = {Seely, D and Ennis, JE and McDonell, E and Fazekas, A and Zhao, L and Asmis, T and Auer, RC and Fergusson, D and Kanji, S and Maziak, DE and Ramsay, T and Chamberland, P and Spooner, C and Threader, J and Seely, A}, title = {Intervention Development Process for a Pragmatic Randomized Controlled Trial: The Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial.}, journal = {Journal of alternative and complementary medicine (New York, N.Y.)}, volume = {25}, number = {S1}, pages = {S112-S123}, doi = {10.1089/acm.2018.0419}, pmid = {30870012}, issn = {1557-7708}, mesh = {Humans ; *Integrative Oncology ; *Perioperative Care ; Pilot Projects ; Quality of Life ; *Randomized Controlled Trials as Topic ; Thoracic Neoplasms/surgery ; Thoracic Surgical Procedures ; }, abstract = {BACKGROUND: Use of complementary therapies is high among people with cancer despite research gaps. The Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial will evaluate the impact of an integrative care intervention delivered by naturopathic doctors (NDs) in conjunction with usual care for patients undergoing surgery for lung, gastric, and esophageal cancer.

OBJECTIVES: To describe the multistep, multidisciplinary process of defining the integrative care intervention to be used in the Thoracic POISE trial using a principle-based approach that is pragmatic, holistic, safe, feasible, evidence driven, and consensus based.

METHODS: An Intervention Development Committee (IDC) made up of a multidisciplinary team of health care providers (NDs, surgeons, oncologists, nurses, dietitians, physiotherapists, pharmacists, and psychologists), researchers, and patients was established to oversee the process. Potential intervention components were identified through a clinical practice survey and expert opinion. Systematic literature reviews were conducted and scores assigned based on the following criteria: usage, safety, goals, feasibility/scalability, and evidence. The IDC selected an intervention to be piloted that consists of a standard palette including core and optional components. Safety, known risks, and interactions with pharmaceuticals were evaluated using industry and professional monographs, a scoping literature review, and consultations with hospital pharmacists.

RESULTS: The clinical practice survey and expert opinion identified 28 components for consideration. Following literature reviews, scoring, consensus from the IDC, and safety and interaction considerations, an intervention palette consisting of core and optional components was defined. The intervention options vary based on the patient's phase of treatment and symptom-specific needs. The intervention includes supplements, physical recommendations (exercise), nutritional counseling, and psychological support (audio scripts).

CONCLUSION: Through a multistep, multidisciplinary process an integrative care intervention was developed for the Thoracic POISE trial. The intervention will be piloted in a single-arm feasibility study, followed by a single-center randomized controlled trial (RCT), and finally a multicenter RCT.}, } @article {pmid30865655, year = {2019}, author = {Maaravi, Y and Idan, O and Hochman, G}, title = {And sympathy is what we need my friend-Polite requests improve negotiation results.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0212306}, pmid = {30865655}, issn = {1932-6203}, mesh = {Adult ; Anger ; Cues ; Emotions ; *Empathy ; Female ; Friends/psychology ; Humans ; Interpersonal Relations ; Israel ; Language ; Male ; Middle Aged ; Negotiating/methods/*psychology ; Perception ; Persuasive Communication ; Psycholinguistics ; Young Adult ; }, abstract = {The wording negotiators use shapes the emotions of their counterparts. These emotions, in turn, influence their counterparts' economic decisions. Building on this rationale, we examined how the language used during negotiation affects discount rate and willingness to engage in future deals. In three studies, participants assumed the role of retailers. Alleged counterparts (actually a computerized program) asked for a discount under three conditions: request, want, and demand. Results show that less extreme language (request/want) resulted in better outcomes than demanding a discount. Moreover, while the language used by the customer had an effect on experienced emotions, the positive emotions (sympathy and empathy) participants felt toward the customer mediated the relationship between the linguistic cue and the negotiation outcome. Our results inform both psycholinguistic research and negotiation research by demonstrating the causal role of linguistic cues in activating concept-knowledge relevant to different emotional experiences, and point to the down-the-line impact on shaping negotiation preferences.}, } @article {pmid30864836, year = {2019}, author = {Dong, Y and Zhang, WW and Wang, J and Sun, JY and He, ZY and Wu, SG}, title = {The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.}, journal = {Future oncology (London, England)}, volume = {15}, number = {14}, pages = {1629-1639}, doi = {10.2217/fon-2018-0967}, pmid = {30864836}, issn = {1744-8301}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/mortality/*therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Postoperative Care ; Prognosis ; Radiotherapy, Adjuvant ; Recurrence ; SEER Program ; }, abstract = {Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.}, } @article {pmid30859170, year = {2018}, author = {Acar, T and Acar, N and Sezgin, G and Gokova, MB and Kucukzeybek, BB and Haciyanli, M}, title = {Treatment choice in metaplastic breast cancer: A report of 5 cases.}, journal = {Northern clinics of Istanbul}, volume = {5}, number = {4}, pages = {365-369}, pmid = {30859170}, issn = {2536-4553}, abstract = {Metaplastic breast carcinoma (MBC) is a general term defining a heterogeneous group that includes biphasic lesions, with both malignant epithelial and mesenchymal tissue components. Although its clinical findings are similar to those present in invasive ductal carcinoma, it rarely presents with the findings of inflammatory breast cancer. It is generally seen in the fifth decade. MBC spreads via lymph and blood circulation. Most common distant metastasis areas include lungs and the bone. Although the treatment generally relies on the same principles applied in invasive ductal carcinoma, a more aggressive treatment should be employed in at-risk groups due to higher rates of local recurrence. In this study, we aimed to discuss clinicopathological features and treatment approach in 5 women with MBC.}, } @article {pmid30856136, year = {2019}, author = {Aplin, FP and Singh, D and Della Santina, CC and Fridman, GY}, title = {Combined ionic direct current and pulse frequency modulation improves the dynamic range of vestibular canal stimulation.}, journal = {Journal of vestibular research : equilibrium & orientation}, volume = {29}, number = {2-3}, pages = {89-96}, pmid = {30856136}, issn = {1878-6464}, support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Animals ; Chinchilla ; Electric Stimulation/instrumentation ; Eye Movements ; Head Movements/physiology ; Ion Channel Gating/*physiology ; Otologic Surgical Procedures/instrumentation ; Prostheses and Implants ; Reflex, Vestibulo-Ocular/*physiology ; Rotation ; Semicircular Canals/*physiology ; Vestibular Evoked Myogenic Potentials/*physiology ; Vestibular Function Tests ; Vestibular Nerve/physiology ; Vestibule, Labyrinth/physiology ; }, abstract = {BACKGROUND: Vestibular prostheses emulate normal vestibular function by electrically stimulating the semicircular canals using pulse frequency modulation (PFM). Spontaneous activity at the vestibular nerve may limit the dynamic range elicited by PFM. One proposed solution is the co-application of ionic direct current (iDC) to inhibit this spontaneous activity.

OBJECTIVE: We aimed to test the hypothesis that a tonic iDC baseline delivered in conjunction with PFM to the vestibular semicircular canals could improve the dynamic range of evoked eye responses.

METHODS: Gentamicin-treated chinchillas were implanted with microcatheter electrodes in the vestibular semicircular canals through which pulsatile and iDC current was delivered. PFM was used to modulate vestibulo-ocular reflex (VOR) once it was adapted to a preset iDC and pulse-frequency baseline. Responses to stimulation were assessed by recording the evoked VOR eye direction and velocity.

RESULTS: PFM produced VOR responses aligned to the stimulated canal. Introduction of an iDC baseline lead to a small but statistically significant increase in eye response velocity, without influencing the direction of eye rotation.

CONCLUSIONS: Tonic iDC baselines increase the dynamic range of encoding head velocity evoked by pulsatile stimulation, potentially via the inhibition of spontaneous activity in the vestibular nerve.}, } @article {pmid30855389, year = {2019}, author = {Myers, PL and Park, RH and Mitchell, DC and Nghiem, BT and Amalfi, AN}, title = {Would Plastic Surgeons Choose Breast Conservation Therapy?.}, journal = {Annals of plastic surgery}, volume = {82}, number = {4S Suppl 3}, pages = {S202-S207}, doi = {10.1097/SAP.0000000000001922}, pmid = {30855389}, issn = {1536-3708}, mesh = {Adult ; *Attitude of Health Personnel ; Breast Neoplasms/*surgery ; *Choice Behavior ; *Clinical Decision-Making ; Female ; Health Care Surveys ; Humans ; Male ; *Mastectomy, Segmental ; Middle Aged ; *Surgery, Plastic ; }, abstract = {BACKGROUND: Breast conservation therapy is defined as partial mastectomy with subsequent radiation therapy and is the treatment for early-stage breast cancer. However, the unwanted risks of radiation must be considered as well as the impact on future breast reconstruction options. The purpose of this study was to assess the preference of plastic surgeons when given the hypothetical diagnosis of breast cancer.

METHODS: A survey assessing treatment preference of 3 hypothetical breast cancer diagnosis scenarios was designed and distributed by American Society of Plastic Surgeons via e-mail invite to its members.

RESULTS: The risk of cancer recurrence was the most common reason for treatment preferences of all three choices. However, for ductal carcinoma in situ, unilateral mastectomy with implant-based reconstruction is the preferred option with the second most influential reason of avoiding the risks of radiation therapy. For invasive ductal carcinoma node negative, unilateral mastectomy with implant-based reconstruction was the preferred option also due to risks of radiation therapy and anxiety of future surveillance. For invasive ductal carcinoma node positive, bilateral mastectomy with implant-based reconstruction was the preferred choice because of anxiety of future surveillance and also risks of radiation therapy.

CONCLUSIONS: In general, plastic surgeons did not prefer breast conservation therapy for in situ and early-stage breast cancer. Although the most common rationale for total mastectomy was risk of cancer recurrence for all disease severity, risks of radiation therapy are real and play an integral role in the decision-making process. In understanding our own biases, we can help better empathize with patients in consultation for breast reconstruction.}, } @article {pmid30854649, year = {2019}, author = {Levontin, L and Nakash, O and Danziger, S}, title = {It takes two to self-disclose: Incremental theorists facilitate others' self-disclosure more than do entity theorists.}, journal = {Journal of personality}, volume = {87}, number = {6}, pages = {1264-1276}, doi = {10.1111/jopy.12473}, pmid = {30854649}, issn = {1467-6494}, support = {847/16 to Levontin//Israel science foundation/International ; 2006/6 to Nakash//Israeli National Institute for Health Policy and Health Services Research/International ; }, mesh = {Adult ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; *Personality ; *Self Disclosure ; *Social Perception ; }, abstract = {OBJECTIVE: We tested the prediction that incremental theorists are more likely to facilitate others' self-disclosure than are entity theorists.

METHOD: We conducted three studies: (a) a field study that examined client's self-disclosure (N = 122; Mage  = 41.9, 67.8% woman; Israelis) during an intake interview with a professional therapist (N = 38; Mage  = 46.2, 84.20% woman; Israelis), (b) a survey of adults (N = 120; Mage  = 37.14, 57.6% female) who reported self-perceptions and behaviors during conversations and their perceptions of others' self-disclosure. In both studies participants reported their implicit theories, and (c) an experiment (N = 250; Mage  = 28.27, 56.6% female) in which participants whose implicit theories were manipulated reported their opening behaviors during a conversation and their perceptions of others' self-disclosure.

RESULTS: Ones' incremental theory of personality was positively related to another's self-disclosure, to one's opening and disclosure-encouraging behaviors, and was negatively related to one's perceptions of others' self-protection tendency. Furthermore, one's opening behaviors and perceptions of others' self-protection tendencies mediated the effect of one's incremental theory on others' self-disclosure.

CONCLUSION: Those who believe people can grow and change, can influence others to trust their personal information with them, even when the information is negative.}, } @article {pmid30854057, year = {2019}, author = {Yamagishi, Y and Einama, T and Yamasaki, T and Koiwai, T and Hiratsuka, M and Fukumura, M and Kono, T and Ueno, H and Yamamoto, J and Tsuda, H}, title = {Metachronous bilateral triple-negative breast cancer associated with neurofibromatosis type 1: A case report.}, journal = {Oncology letters}, volume = {17}, number = {3}, pages = {2818-2824}, pmid = {30854057}, issn = {1792-1074}, abstract = {The present study reports a case of metachronous bilateral breast cancer associated with neurofibromatosis type 1 (NF1). A 67-year-old female, who had undergone a radical mastectomy of the left breast 34 years ago due to breast cancer, presented with a tumor of the right breast. The clinical stage of the original breast cancer was T2N0M0 stage IIA and adjuvant chemotherapy had not been not administered. With regard to the right-sided breast tumor, on physical examination, multiple neurofibromas and café-au-lait spots were found to be scattered over the skin. A 2-cm tumor was palpable. The preoperative histopathological diagnosis of the right-sided breast tumor was invasive ductal carcinoma, T2N0M0 stage IIA, with negative results for hormone receptors and human epidermal growth factor receptor 2. The patient underwent a modified radical mastectomy and axillary node dissection, and received adjuvant chemotherapy. The bilateral tumors were similar in histology and immunophenotype, each being histological grade 3, triple-negative and with a basal-like subtype. Based on a literature review of 90 breast cancers in 84 patients with NF1 (84 patients, 90 breasts), younger age onset, advanced clinical stage and hormone receptor negativity were characteristic features. Bilateral cancer occurred in 8.3% of patients and was characterized by ER negativity, earlier stage and younger age compared with patients with unilateral cancer.}, } @article {pmid30843776, year = {2018}, author = {Menichetti, F and Bertolino, G and Sozio, E and Carmignani, C and Rosselli Del Turco, E and Tagliaferri, E and Sbrana, F and Ripoli, A and Barnini, S and Desideri, I and Dal Canto, L and Tascini, C and , }, title = {Impact of infectious diseases consultation as a part of an antifungal stewardship programme on candidemia outcome in an Italian tertiary-care, University hospital.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {30}, number = {5}, pages = {304-309}, doi = {10.1080/1120009X.2018.1507086}, pmid = {30843776}, issn = {1973-9478}, mesh = {Aged ; Antifungal Agents/*therapeutic use ; Antimicrobial Stewardship/methods ; Candida/drug effects ; Candidemia/*drug therapy ; Communicable Diseases/*drug therapy ; Female ; Fluconazole/therapeutic use ; Hospitals, University ; Humans ; Italy ; Male ; Referral and Consultation ; Retrospective Studies ; }, abstract = {Candidemia is a major cause of in-hospital mortality. Antifungal stewardship programme (AFSP) providing infectious diseases consultation (IDC) might improve the outcome. We evaluate the impact on candidemia mortality of IDC as part of AFSP restricting the use of all antifungals with exception of fluconazole. We retrospectively reviewed the charts of patients with documented candidemia in our hospital during the period 2012-2014 evaluating the impact of several variables on 30-days in-hospital mortality. We reviewed data on 276 patients with documented candidemia: 200 (72%) were treated without IDC and 76 (28%) with IDC. In the group without IDC, 52 patients (26%) received no antifungal therapy. Antifungals used for treating candidemia were (no IDC/IDC): azoles (74%/42%); echinocandins (0%/46%); liposomal and lipidic complex amphotericin B (0%/12%). The 30-day in-hospital mortality was respectively (no IDC/IDC) 37% vs. 20% (p = 0.011). The multivariate analysis confirmed IDC as independent factor protecting from death (OR 0.511, 95% CI 0.251-0.994; p = 0.046), together with fungemia due to non-albicans Candida (OR 0.565, 95% CI 0.327-0.977; p = 0.042). Age >65 years was associated with a higher risk of death (OR 1.989, 95% CI 1.055-3.895; p = 0.038). The additional cost for the use of echinocandins driven by IDC in the study period was €207,000. IDC, as a part of a restrictive front-end antimicrobial stewardship programme (ASP), providing a timely right choice of antifungal therapy, increases the cost of antifungal drugs but might be a contributing protective factor from mortality due to candidemia. Efforts to increase the number of IDC in patients with candidemia seems to be warranted.}, } @article {pmid30843116, year = {2019}, author = {Goodfellow, J and Gorrie, G and Leach, V and Patel, S and Mackay, G}, title = {Cancer and motor neuron disease-causal or coincidental? Two contrasting cases.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {7}, pages = {1461-1463}, pmid = {30843116}, issn = {1590-3478}, mesh = {Breast Neoplasms/*complications/immunology/pathology ; Carcinoma, Ductal, Breast/*complications/immunology/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*complications/immunology/pathology/therapy ; Middle Aged ; Motor Neuron Disease/*complications/etiology/immunology ; *Paraneoplastic Syndromes, Nervous System/immunology ; Small Cell Lung Carcinoma/*complications/immunology/pathology/therapy ; }, abstract = {INTRODUCTION: Motor neuron disease (MND) can occur in patients with cancer, but there is minimal evidence that this is more than by chance. We contrast two cases of motor neuronopathies occurring in the context of systemic malignancy and argue that in one case the cause was most likely paraneoplastic, while in the other it was not. CASE 1: A 61-year-old woman developed progressive walking difficulties over 9 months with weakness and stiffness in her legs. EMG showed fibrillations and positive sharp waves in multiple lower limb muscles bilaterally, with neurogenic units and a reduced recruitment pattern. An invasive ductal carcinoma of the breast was identified and she continued to deteriorate neurologically with worsening mobility, upper limb spasticity and fasciculations. She died approximately 26 months after symptom onset. CASE 2: A 57-year-old woman developed weight loss and weakness of her right arm without any sensory symptoms. At presentation, she had wasting and fasciculations in her right upper limb muscles, with normal reflexes, normal left upper limb and lower limb examination. Over the following week, she developed left upper limb weakness and fasciculations, brisk knee reflexes, and flexor plantar responses. Her EMG showed upper and lower limb denervation. She was found to have anti-Hu and anti-CV2 antibodies present in serum. A PET-CT showed active uptake in lymph nodes in the right hilum. Biopsy confirmed a small cell lung cancer. She had chemoradiation therapy and the tumour went into remission. She has remained well on follow-up 24 months later, regaining weight and strength after her chemotherapy. She continues to be monitored for cancer recurrence, but thus far appears to be in remission.

CONCLUSION: In cases with rapidly progressive MND, particularly of upper limb onset, consideration should be given to testing anti-neuronal antibodies and searching for an occult tumour.}, } @article {pmid30842485, year = {2019}, author = {Rossi, A and Dupaty, L and Aillot, L and Zhang, L and Gallien, C and Hallek, M and Odenthal, M and Adriouch, S and Salvetti, A and Büning, H}, title = {Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {3631}, pmid = {30842485}, issn = {2045-2322}, mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/virology ; Capsid/*immunology ; Capsid Proteins/*immunology ; Dendritic Cells/*immunology/virology ; Dependovirus/genetics/*immunology ; Genetic Vectors/*administration & dosage/*immunology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; *Transduction, Genetic ; }, abstract = {AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8[+] T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.}, } @article {pmid30830381, year = {2018}, author = {More, TH and Taware, R and Taunk, K and Chanukuppa, V and Naik, V and Mane, A and Rapole, S}, title = {Investigation of altered urinary metabolomic profiles of invasive ductal carcinoma of breast using targeted and untargeted approaches.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {14}, number = {8}, pages = {107}, pmid = {30830381}, issn = {1573-3890}, support = {RGYI BT/PR6384/GBD/27/409/2012//Department of Biotechnology, Ministry of Science and Technology/International ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Case-Control Studies ; Chromatography, Liquid/*methods ; Female ; Gas Chromatography-Mass Spectrometry/*methods ; Humans ; Metabolic Networks and Pathways ; *Metabolome ; ROC Curve ; Tandem Mass Spectrometry/*methods ; }, abstract = {INTRODUCTION: Invasive ductal carcinoma (IDC) is a type of breast cancer, usually detected in advanced stages due to its asymptomatic nature which ultimately leads to low survival rate. Identification of urinary metabolic adaptations induced by IDC to understand the disease pathophysiology and monitor therapy response would be a helpful approach in clinical settings. Moreover, its non-invasive and cost effective strategy better suited to minimize apprehension among high risk population.

OBJECTIVE: This study aims toward investigating the urinary metabolic alterations of IDC by targeted (LC-MRM/MS) and untargeted (GC-MS) approaches for the better understanding of the disease pathophysiology and monitoring therapy response.

METHODS: Urinary metabolic alterations of IDC subjects (63) and control subjects (63) were explored by targeted (LC-MRM/MS) and untargeted (GC-MS) approaches. IDC specific urinary metabolomics signature was extracted by applying both univariate and multivariate statistical tools.

RESULTS: Statistical analysis identified 39 urinary metabolites with the highest contribution to metabolomic alterations specific to IDC. Out of which, 19 metabolites were identified from targeted LC-MRM/MS analysis, while 20 were identified from the untargeted GC-MS analysis. Receiver operator characteristic (ROC) curve analysis evidenced 6 most discriminatory metabolites from each type of approach that could differentiate between IDC subjects and controls with higher sensitivity and specificity. Furthermore, metabolic pathway analysis depicted several dysregulated pathways in IDC including sugar, amino acid, nucleotide metabolism, TCA cycle etc. CONCLUSIONS: Overall, this study provides valuable inputs regarding altered urinary metabolites which improved our knowledge on urinary metabolomic alterations induced by IDC. Moreover, this study identified several dysregulated metabolic pathways which offer further insight into the disease pathophysiology.}, } @article {pmid30830375, year = {2018}, author = {Paul, A and Kumar, S and Raj, A and Sonkar, AA and Jain, S and Singhai, A and Roy, R}, title = {Alteration in lipid composition differentiates breast cancer tissues: a [1]H HRMAS NMR metabolomic study.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {14}, number = {9}, pages = {119}, pmid = {30830375}, issn = {1573-3890}, mesh = {Breast Neoplasms/diagnosis/*metabolism ; Choline/analysis/metabolism ; Female ; Glutamic Acid/analysis/metabolism ; Glycine/analysis/metabolism ; Humans ; Lipids/*analysis ; *Metabolomics ; Middle Aged ; Multivariate Analysis ; Proton Magnetic Resonance Spectroscopy ; Taurine/analysis/metabolism ; }, abstract = {INTRODUCTION: Breast cancer is the most frequent diagnosed cancer among women with a mortality rate of 15% of all cancer related deaths in women. Breast cancer is heterogeneous in nature and produces plethora of metabolites allowing its early detection using molecular diagnostic techniques like magnetic resonance spectroscopy.

OBJECTIVES: To evaluate the variation in metabolic profile of breast cancer focusing on lipids as triglycerides (TG) and free fatty acids (FFA) that may alter in malignant breast tissues and lymph nodes from adjacent benign breast tissues by HRMAS [1]H NMR spectroscopy.

METHODS: The [1]H NMR spectra recorded on 173 tissue specimens comprising of breast tumor tissues, adjacent tissues, few lymph nodes and overlying skin tissues obtained from 67 patients suffering from breast cancer. Multivariate statistical analysis was employed to identify metabolites acting as major confounders for differentiation of malignancy.

RESULT: Reduction in lipid content were observed in malignant breast tissues along with a higher fraction of FFA. Four small molecule metabolites e.g., choline containing compounds (Chocc), taurine, glycine, and glutamate were also identified as major confounders. The test set for prediction provided sensitivity and specificity of more than 90% excluding the lymph nodes and skin tissues.

CONCLUSION: Fatty acids composition in breast cancer using in vivo magnetic resonance spectroscopy (MRS) is gaining its importance in clinical settings (Coum et al. in Magn Reson Mater Phys Biol Med 29:1-4, 2016). The present study may help in future for precise evaluation of lipid classification including small molecules as a source of early diagnosis of invasive ductal carcinoma by employing in vivo magnetic resonance spectroscopic methods.}, } @article {pmid30829873, year = {2019}, author = {Manganaro, MS and Millet, JD and Manganaro, MS}, title = {Inadvertent Injection of a Breast Implant During Lymphoscintigraphy.}, journal = {Clinical nuclear medicine}, volume = {44}, number = {7}, pages = {585-586}, doi = {10.1097/RLU.0000000000002511}, pmid = {30829873}, issn = {1536-0229}, mesh = {Adult ; Breast Implants/*adverse effects ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Female ; Humans ; *Lymphoscintigraphy ; Radiopharmaceuticals/pharmacokinetics ; Technetium Tc 99m Sulfur Colloid/pharmacokinetics ; }, abstract = {A 34-year-old woman with history of bilateral saline implants, invasive ductal carcinoma of the right breast, and suspicious left breast calcifications was referred for left breast lymphoscintigraphy before bilateral mastectomy. A total of 3.2 mCi of Tc-filtered sulfur colloid was administered with 3 subdermal injections in the superior, lateral, and inferior periareolar left breast in the late afternoon preceding the day of surgery. Imaging identified radiotracer uptake within a dense, circular area deep to the injection sites within the left breast, compatible with implant puncture and radiotracer administration within the indwelling breast implant.}, } @article {pmid30825809, year = {2019}, author = {Owen, WA and Brazeal, HA and Shaw, HL and Lee, MV and Appleton, CM and Holley, SO}, title = {Focal breast pain: imaging evaluation and outcomes.}, journal = {Clinical imaging}, volume = {55}, number = {}, pages = {148-155}, doi = {10.1016/j.clinimag.2019.02.008}, pmid = {30825809}, issn = {1873-4499}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Cancer Pain/diagnostic imaging/etiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; Humans ; Incidental Findings ; Mammography/methods ; Mastodynia/*diagnostic imaging/etiology ; Middle Aged ; Prognosis ; Retrospective Studies ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVES: To determine the number and characteristics of cancers detected and the optimal imaging evaluation in women presenting with focal breast pain (FBP).

MATERIALS AND METHODS: We performed a retrospective review of 4720 women who underwent imaging for FBP from 2001 to 2013. Women 18 and over with one or two foci of breast pain and no concurrent breast symptoms were included. 944 patients met criteria. We recorded the imaging work-up, presence and type of finding at the site of pain, BI-RADS® assessment, and pathological outcomes. Subsequent imaging and clinical follow up was recorded.

RESULTS: Imaging evaluation consisted of sonogram alone in 286 women, mammogram alone in 231 women, and both in 427 women. 113 women had an imaging finding at the site of pain; 103 were designated benign or probably benign. 12 biopsies of corresponding findings were performed: 9 benign, 1 invasive lobular carcinoma, 1 invasive ductal carcinoma, 1 ductal carcinoma in situ. All three malignancies were seen mammographically; 2 had an ultrasound correlate. At initial evaluation, 4 incidental breast cancers were diagnosed remote from the site of FBP. All were seen on mammogram and 2 of 4 had an ultrasound correlate. On follow up evaluation, 9 cancers were diagnosed at the site of pain and 13 incidental cancers were diagnosed.

CONCLUSION: FBP is rarely associated with malignancy. Targeted ultrasound may be deferred in women 40 and older with FBP, no other clinical findings, and a negative mammogram.}, } @article {pmid30825183, year = {2019}, author = {Ahmadvand, S and Faghih, Z and Montazer, M and Safaei, A and Mokhtari, M and Jafari, P and Talei, AR and Tahmasebi, S and Ghaderi, A}, title = {Importance of CD45RO+ tumor-infiltrating lymphocytes in post-operative survival of breast cancer patients.}, journal = {Cellular oncology (Dordrecht)}, volume = {42}, number = {3}, pages = {343-356}, pmid = {30825183}, issn = {2211-3436}, support = {95-11864//Shiraz University of Medical Sciences/ ; ICR-100-508//Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology/surgery ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Kaplan-Meier Estimate ; Leukocyte Common Antigens/*metabolism ; Lymphocytes, Tumor-Infiltrating/*metabolism ; Mastectomy ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: In recent years, the prognostic/predictive significance of tumor infiltrating lymphocytes (TILs) has become a topic of interest. Here, we aimed to evaluate the prognostic significance of CD3+, CD8+, CD45RO+ and Foxp3+ TILs in breast cancer, as well as the relation of these markers to other clinicopathological features of this disease.

METHODS: FFPE tumor samples from 94 females with invasive ductal carcinoma of the breast were retrospectively selected and immunohistochemically assessed for CD3, CD8, CD45RO and Foxp3 expression. Digital photos were acquired from the center (CT) and invasive margins (IM) of the tumors, after which positive cells were counted using ImageJ software.

RESULTS: We found that greater infiltrations of target lymphocyte subpopulations were associated with TNM stage III, lymph node metastasis, high histological grade, ER negativity and HER2 positivity. The ratios of CD8+ cytotoxic T cells to CD3+, CD45RO+ and Foxp3+ TILs were found to be relatively higher in tumors exhibiting the aforementioned characteristics. In univariate survival analyses, CD8+ TILs in the IM and total CD45RO+ TILs were found to be significantly associated with overall survival (OS). Infiltration of CD45RO+ TILs in the CT and lymph node status were variables that significantly correlated with disease-free survival (DFS). Multiple Cox regression analyses revealed independent significant prognostic effects of total CD45RO+ TILs and lymph node status (HR of 3.24 and 3.19, respectively) in predicting OS. Infiltration of CD45RO+ TILs in the CT (HR 3.12) and lymph node status (HR 3.15) also exhibited significant prognostic effects on DFS.

CONCLUSION: From our data we conclude that CD45RO+ TILs serve as prognostic factors for predicting OS and DFS of breast cancer patients.}, } @article {pmid30820924, year = {2019}, author = {Murakami, W and Tozaki, M and Nakamura, S and Ide, Y and Inuzuka, M and Hirota, Y and Murakami, K and Takahama, N and Ohgiya, Y and Gokan, T}, title = {The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {26}, number = {5}, pages = {552-561}, pmid = {30820924}, issn = {1880-4233}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/*genetics/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics/pathology ; Female ; Follow-Up Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Humans ; Japan ; *Magnetic Resonance Imaging ; Mammography ; Mass Screening/methods ; Middle Aged ; *Mutation ; Public Health Surveillance/methods ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: There is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.

METHODS: We retrospectively reviewed 93 female (median age 43 years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017. The study population was composed of 112 breast cancers. Mammography and MRI were reviewed by examiners blinded to patients' clinical history. Final surgical or biopsy histopathology served as the reference standard in all the patients.

RESULTS: Fifty-nine breast cancers met selection criteria; of these, 30 were BRCA1-associated tumors, and 29 were BRCA2-associated tumors. Invasive ductal carcinoma was the most prevalent type in both BRCA1 and BRCA2. There were statistically significant differences in phenotype, nuclear grade, and Ki-67 labeling index between BRCA1 and BRCA2 mutation carriers. Additionally, imaging findings on mammography and MRI were statistically different. Tumors in BRCA2 carriers demonstrated mammographic calcifications more frequently, while those in BRCA1 carriers demonstrated a mass or architectural distortion (P < 0.001). Enhancement pattern on MRI also significantly differed between the two subgroups (P = 0.006). The size of MRI-detected lesions was statistically smaller than the size of those detected by other modalities (P = 0.004).

CONCLUSIONS: The imaging and histological characteristics of BRCA1/2 mutation carriers were consistent with other countries' studies. MRI-detected lesions were significantly smaller than lesions detected by non-MRI modality. All lesions in BRCA1 mutation carriers could be detected by MRI.}, } @article {pmid30820448, year = {2019}, author = {Desmedt, C and Pingitore, J and Rothé, F and Marchio, C and Clatot, F and Rouas, G and Richard, F and Bertucci, F and Mariani, O and Galant, C and Fribbens, C and O'Leary, B and van den Eynden, G and Salgado, R and Turner, NC and Piccart, M and Vincent-Salomon, A and Pruneri, G and Larsimont, D and Sotiriou, C}, title = {ESR1 mutations in metastatic lobular breast cancer patients.}, journal = {NPJ breast cancer}, volume = {5}, number = {}, pages = {9}, pmid = {30820448}, issn = {2374-4677}, support = {MR/N002121/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Invasive lobular breast cancer (ILC) represents the second most common histology of breast cancer after invasive ductal breast cancer (IDC), accounts for up to 15% of all invasive cases and generally express the estrogen receptor (ER, coded by the ESR1 gene). ESR1 mutations have been associated with resistance to endocrine therapy, however these have not been specifically evaluated in ILC. We assessed the frequency of ESR1 mutations by droplet digital PCR in a retrospective multi-centric series of matched primary tumor and recurrence samples (n = 279) from 80 metastatic ER-positive ILC patients. We further compared ESR1 mutations between IDC and ILC patients in metastatic samples from MSKCC-IMPACT (n = 595 IDC and 116 ILC) and in ctDNA from the SoFEA and PALOMA-3 trials (n = 416 IDC and 76 ILC). In the retrospective series, the metastases from seven patients (9%) harbored ESR1 mutations, which were absent from the interrogated primary samples. Five patients (6%) had a mutation in the primary tumor or axillary metastasis, which could not be detected in the matched distant metastasis. In the MSKCC-IMPACT cohort, as well as in the SoFEA and PALOMA-3 trials, there were no differences in prevalence and distribution of the mutations between IDC and ILC, with D538G being the most frequent mutation in both histological subtypes. To conclude, no patient had an identical ESR1 mutation in the early and metastatic disease in the retrospective ILC series. In the external series, there was no difference in terms of prevalence and type of ESR1 mutations between ILC and IDC.}, } @article {pmid30817241, year = {2019}, author = {Muglia, VF and Reis, RB}, title = {Re: Long-Term Surveillance of Complex Cystic Renal Masses and Heterogeneity of Bosniak 3 LesionsD. K. Pruthi, Q. Liu, I. D. C. Kirkpatrick, J. Gelfond and D. E. Drachenberg J Urol 2018; 200: 1192-1199.}, journal = {The Journal of urology}, volume = {202}, number = {1}, pages = {171-172}, doi = {10.1097/JU.0000000000000201}, pmid = {30817241}, issn = {1527-3792}, mesh = {Humans ; *Kidney Diseases, Cystic ; *Kidney Neoplasms ; }, } @article {pmid30813596, year = {2019}, author = {Myers, MB and McKim, KL and Banda, M and George, NI and Parsons, BL}, title = {Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.}, journal = {International journal of molecular sciences}, volume = {20}, number = {5}, pages = {}, pmid = {30813596}, issn = {1422-0067}, mesh = {Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fluorescein/metabolism ; Humans ; Middle Aged ; Mutation/genetics ; *Mutation Rate ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/genetics ; Polymerase Chain Reaction ; *Precision Medicine ; Proto-Oncogene Proteins B-raf/genetics ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10[-5], the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.}, } @article {pmid30810889, year = {2019}, author = {Yang, J and Yin, J}, title = {Discrimination between breast invasive ductal carcinomas and benign lesions by optimizing quantitative parameters derived from dynamic contrast-enhanced MRI using a semi-automatic method.}, journal = {International journal of clinical oncology}, volume = {24}, number = {7}, pages = {815-824}, pmid = {30810889}, issn = {1437-7772}, support = {201601118//Startup Foundation for Doctors of Liaoning Province/ ; }, mesh = {Adult ; Aged ; Breast/*diagnostic imaging/pathology ; Breast Diseases/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging ; Middle Aged ; ROC Curve ; Regression Analysis ; }, abstract = {BACKGROUND: To propose a semi-automatic method for distinguishing invasive ductal carcinomas from benign lesions on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

METHODS: 142 cases were included. In the conventional method, the region of interest for a breast lesion was drawn manually and the corresponding mean time-signal intensity curve (TIC) was qualitatively categorized. Only one quantitative parameter was obtained: the maximum slope of increase (MSI). By contrast, the proposed method extracted the suspicious breast lesion semi-automatically. Besides MSI, more quantitative parameters reflecting perfusion information were derived from the mean TIC and lesion region, including the signal intensity slope (SIslope), initial percentage of enhancement, percentage of peak enhancement, early signal enhancement ratio, and second enhancement percentage. The mean TIC was categorized quantitatively according to the value of SIslope. Regression models were established. The diagnostic performance differed between the new and conventional methods according to the Wilcoxon rank-sum test and receiver operating characteristic analysis.

RESULTS: According to the TIC categorization results, the accuracies of the traditional and the new method were 59.16% and 76.05%, respectively (P < 0.05). The accuracy was 63.35% for MSI, which was derived from the manual method. For the semi-automatic method, the accuracies were 81.0% and 78.9% for the lesion region and the corresponding mean TIC regression models, respectively.

CONCLUSIONS: The results demonstrate that our proposed semi-automatic method is beneficial for discriminating breast IDCs and benign lesions based on DCE-MRI, and this method should be considered as a supplementary tool for subjective diagnosis by clinical radiologists.}, } @article {pmid30807826, year = {2019}, author = {Griggs, RB and Santos, DF and Laird, DE and Doolen, S and Donahue, RR and Wessel, CR and Fu, W and Sinha, GP and Wang, P and Zhou, J and Brings, S and Fleming, T and Nawroth, PP and Susuki, K and Taylor, BK}, title = {Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.}, journal = {Neurobiology of disease}, volume = {127}, number = {}, pages = {76-86}, pmid = {30807826}, issn = {1095-953X}, support = {R01 DA037621/DA/NIDA NIH HHS/United States ; F31 NS083292/NS/NINDS NIH HHS/United States ; R56 NS107398/NS/NINDS NIH HHS/United States ; R01 NS062306/NS/NINDS NIH HHS/United States ; R01 NS045954/NS/NINDS NIH HHS/United States ; T32 NS077889/NS/NINDS NIH HHS/United States ; }, mesh = {Adenylyl Cyclases/*metabolism ; Animals ; Avoidance Learning/drug effects/physiology ; Behavior, Animal/drug effects/physiology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Type 2/complications/*metabolism ; Diabetic Neuropathies/*metabolism ; Guanine Nucleotide Exchange Factors/*metabolism ; Male ; Mice ; Pain Measurement ; Posterior Horn Cells/drug effects/metabolism ; Pyruvaldehyde/*metabolism/pharmacology ; Signal Transduction/drug effects/physiology ; TRPA1 Cation Channel/*metabolism ; }, abstract = {Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca[2+] mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes.}, } @article {pmid30807738, year = {2019}, author = {Influs, M and Masalha, S and Zagoory-Shaon, O and Feldman, R}, title = {Dialogue intervention to youth amidst intractable conflict attenuates stress response to outgroup.}, journal = {Hormones and behavior}, volume = {110}, number = {}, pages = {68-76}, doi = {10.1016/j.yhbeh.2019.02.013}, pmid = {30807738}, issn = {1095-6867}, mesh = {Adolescent ; Arabs/psychology ; Armed Conflicts/*psychology ; *Communication ; Empathy/physiology ; Female ; Geography ; Humans ; *Interpersonal Relations ; Israel ; Jews/psychology ; Male ; Negotiating/methods/psychology ; Psychology, Adolescent/*methods ; Residence Characteristics ; Social Behavior ; Stress, Psychological/psychology/*therapy ; }, abstract = {Encounter with outgroup has been shown to elicit physiological stress response and when outgroup is perceived as threatening to one's own family and community, stress is higher. In such contexts, becoming familiar and learning to empathize with the other side may reduce stress. Building on the long-lasting Israeli-Palestinian conflict, we developed an eight-week group intervention focused on dialogue and empathy and tested it within a randomized controlled trial. Eighty-eight Israeli-Jewish and Arab-Palestinian adolescents (16-18 years) were randomly assigned to intervention or control groups. Before(T1) and after(T2) intervention, one-on-one interaction with outgroup member was videotaped, cortisol levels assessed five times during a 2.5-hour session involving exposure to outgroup stimuli, and adolescents were interviewed regarding national conflict. Intervention reduced cortisol response to social contact and reminders of outgroup (F = 4.92, p = .032, Eta[2] = 0.109). This HPA-activity suppression was defined by two pathways. First, intervention had a direct impact on cortisol decrease; and second, intervention increased youth's behavioral empathy during one-on-one interaction with outgroup member and this empathic response mediated the effect of intervention on cortisol reduction. Adolescents' belief in the potential for reconciliation at T1 predicted greater empathy at T2. Our study provides the first evidence-based intervention for youth growing up amidst intractable conflict and demonstrates its impact on adolescents' physiological stress response to outgroup. Results contribute to research on the neurobiology of ingroup/outgroup relations, highlight the key role of dialogical empathy and social interactions for interventions targeting youth, and emphasize the importance of enhancing motivation for social inclusion for initiating positive behavioral and physiological processes. Clinical Trials Registry (NCT02122887; https://clinicaltrials.gov).}, } @article {pmid30806064, year = {2019}, author = {Luangxay, T and Virachith, S and Hando, K and Vilayvong, S and Xaysomphet, P and Arounlangsy, P and Phongsavan, K and Mieno, MN and Honma, N and Kitagawa, M and Sawabe, M}, title = {Subtypes of Breast Cancer in Lao P.D.R.: A Study in a Limited-Resource Setting.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {20}, number = {2}, pages = {589-594}, pmid = {30806064}, issn = {2476-762X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*classification/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Female ; Follow-Up Studies ; Health Resources ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Young Adult ; }, abstract = {Aim: The purpose of this study is to evaluate the prevalence of the immunohistochemical subtypes of breast cancer among Lao women by using immunohistochemistry (according to the St. Gallen 2017 guidelines) and to study their correlation to clinicopathological features in order to help guide better treatment plans for patients. Materials and methods: Formalin-fixed and paraffin embedded tissue blocks of 76 cases of primary invasive breast cancer were retrieved from the University of Health Sciences, Vientiane, Lao PDR, from 2013 to 2016. Patients’ information and previous histological reports were reviewed. Immunohistochemistry was done using antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu) and Ki-67 (MIB-1). Results: The mean age of the patients was 49 years, and the major histologic type was invasive ductal carcinoma, NOS (90.7%). The proportion of each subtype was hormone receptor-positive and HER2-negative, 44.7%; hormone receptor-positive and HER2-positive, 3.9%; hormone receptor-negative and HER2-positive, 13.2%; and triple-negative, 38.2%. ER was positive in 40.8% of the cases, while PR was positive in 47.4%. More than half of the cases were poorly differentiated cancer (65.8%), followed by moderately differentiated (34.2%). Tumors presented with pT2 (60.5%), followed by pT3 (25.0%) and pT4 (7.9%). Conclusion: Breast cancer among Lao women is characterized by a large percentage of the triple-negative subtype that is less susceptible to hormonal treatments. The empirical treatment with tamoxifen should be reconsidered since it would be less effective to these patients. More importantly, basic pathology services should be the first requirement in Lao PDR in order to provide adequate care.}, } @article {pmid30799833, year = {2018}, author = {Zongo, N and Windsouri, M and Bambara, HA and Some, OR and Bambara, AT and Ouangré, E and Zida, M and Bonkoungou, G and Sanou, A and Dubot, C and Dem, A}, title = {So-called "historical" necrotic breast cancers: a terrifying actuality in Africa. The case of Burkina Faso.}, journal = {Medecine et sante tropicales}, volume = {28}, number = {4}, pages = {434-438}, doi = {10.1684/mst.2018.0854}, pmid = {30799833}, issn = {2261-2211}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology ; Breast Neoplasms/mortality/*pathology/therapy ; Burkina Faso ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant/statistics & numerical data ; Female ; Humans ; Leukocytosis/epidemiology ; Longitudinal Studies ; Mastectomy/statistics & numerical data ; Middle Aged ; *Necrosis ; Palliative Care/statistics & numerical data ; Time-to-Treatment ; Young Adult ; }, abstract = {Study the epidemiological, diagnostic, and treatment features and outcomes of necrotic breast cancer in women. This observational, longitudinal, and descriptive study covered the period from January, 2011, to the end of May, 2016 at the Surgery and Gynecology Departments of Yalgado Ouedraogo University Hospital and Schiphra Medical Center. The study included all women with necrotic breast cancers. Survival was calculated by the Kaplan Meier method and survival comparison was possible with the log-rank method. À risk of error of 0.05 was allowed. Necrotic cancer accounted for 9.1% of all breast cancers. The median age of the patients was 46 years old. The median interval before consultation was 12.4 months. The histological type was invasive ductal carcinoma in 90.8% of cases. Surgery was performed in 51 patients (52%). It was a palliative (cleaning) procedure in 92.2% of cases. Chemotherapy was performed in 28 patients. Overall survival was 61.8% at 6 months, 39.5% at 1 year, and 9.2% at 3 years. Median survival was 10 months: 13 months for women with surgery and 6 months for those without it (p<0.001). Necrotic breast cancer is still common in Ouagadougou. Surgery is the mainstay of the treatment. Survival is mediocre. It therefore seems urgent to focus on raising population awareness and organizing screening campaigns.}, } @article {pmid30798329, year = {2019}, author = {Sawai, H and Kurimoto, M and Koide, S and Kiriyama, Y and Haba, S and Matsuo, Y and Morimoto, M and Koide, H and Kamiya, A and Yamao, K}, title = {Invasive Ductal Carcinoma Arising in Mucinous Cystic Neoplasm of Pancreas: A Case Report.}, journal = {The American journal of case reports}, volume = {20}, number = {}, pages = {242-247}, pmid = {30798329}, issn = {1941-5923}, mesh = {Adult ; Carcinoma, Pancreatic Ductal/*pathology ; Cystadenoma, Mucinous/*pathology ; Female ; Humans ; Mutation ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Pancreatic Neoplasms/*pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; }, abstract = {BACKGROUND Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. CASE REPORT A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. CONCLUSIONS We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinicopathological parameter.}, } @article {pmid30789657, year = {2019}, author = {Nguyen, B and Veys, I and Leduc, S and Bareche, Y and Majjaj, S and Brown, DN and Boeckx, B and Lambrechts, D and Sotiriou, C and Larsimont, D and Desmedt, C}, title = {Genomic, Transcriptomic, Epigenetic, and Immune Profiling of Mucinous Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {111}, number = {7}, pages = {742-746}, doi = {10.1093/jnci/djz023}, pmid = {30789657}, issn = {1460-2105}, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/*genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Female ; Genomic Instability/genetics ; Genomics/methods ; Humans ; Lymphatic Metastasis ; Mucin-2/*genetics ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcriptome/genetics ; }, abstract = {Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC.}, } @article {pmid30788093, year = {2019}, author = {Martins, L and Galvão, D and Silva, A and Vieira, B and Reis, Ó and Vitorino, R and Pires, P}, title = {Paraneoplastic opsoclonus-myoclonus syndrome as a rare presentation of breast cancer.}, journal = {Journal of surgical case reports}, volume = {2019}, number = {2}, pages = {rjy365}, pmid = {30788093}, issn = {2042-8812}, abstract = {Opsoclonus-myoclonus paraneoplastic syndrome is a medical condition that includes opsoclonus along with diffuse or focal body myoclonus and truncal titubation with or without ataxia and other cerebellar signs. This rare neurological syndrome is poorly understood and can result in long-term cognitive, behavioral and motor sequelae. We report a case of a 49-year-old woman with anti-Ri antibody opsoclonus-myoclonus syndrome and an invasive ductal carcinoma with axillary nodes involvement. Following the diagnosis of opsoclonus-myoclonus syndrome, a multimodal immunotherapy treatment, with partial remission of the neurological symptoms. The patient underwent lumpectomy and axillary node dissection and the surgical pathology confirmed the diagnosis of breast cancer stage IIA. This was followed by chemotherapy, radiotherapy and hormone therapy with tamoxifen. At the 6 months follow-up there was a partial improvement, anti-Ri antibody was subsequently reported as negative and there was no evidence of disease recurrence.}, } @article {pmid30786684, year = {2018}, author = {Hybiak, J and Domagala, P and Domagala, W}, title = {BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {69}, number = {4}, pages = {347-355}, doi = {10.5114/pjp.2018.81694}, pmid = {30786684}, issn = {1233-9687}, mesh = {BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Humans ; Laser Capture Microdissection ; Poly (ADP-Ribose) Polymerase-1/*genetics ; RNA, Messenger ; }, abstract = {The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR. The relative expression of BRCA1 mRNA was significantly increased in DCIS G2 and DCIS G3 relative to normal breast tissue (p = 0.02, p = 0.001, respectively). Significant differences in BRCA1 expression were observed between DCIS G1 and G2 (p = 0.02) and between DCIS G1 and G3 (p = 0.0007). No significant differences in BRCA1 expression were observed between normal breast tissue and DCIS G1 and between DCIS component and adjacent invasive ductal carcinoma. No significant differences in the relative expression of PARP1 mRNA were observed between groups. Increased BRCA1 mRNA expression (but not PARP1 mRNA) occurs early in the development of breast cancer, i.e. at the noninvasive (DCIS) stage, suggesting a demand for increased activity of a DNA double-strand break repair by homologous recombination. DCIS G1 and normal breast tissue share highly similar BRCA1 and PARP1 expression level. This finding supports the idea that DCIS G1 belongs to a separate family of precursor lesions with low malignant potential.}, } @article {pmid30774698, year = {2019}, author = {Hamza, A and Khawar, S and Sakhi, R and Alrajjal, A and Miller, S and Ibrar, W and Edens, J and Salehi, S and Ockner, D}, title = {Factors affecting the concordance of radiologic and pathologic tumor size in breast carcinoma.}, journal = {Ultrasound (Leeds, England)}, volume = {27}, number = {1}, pages = {45-54}, pmid = {30774698}, issn = {1742-271X}, abstract = {BACKGROUND: Radiologic assessment of tumor size is an integral part of the work-up for breast carcinoma. With improved radiologic equipment, surgical decision relies profoundly upon radiologic/clinical stage. We wanted to see the concordance between radiologic and pathologic tumor size to infer how accurate radiologic/clinical staging is.

MATERIALS AND METHODS: The surgical pathology and ultrasonography reports of patients with breast carcinoma were reviewed. Data were collected for 406 cases. Concordance was defined as a size difference within ±2 mm.

RESULTS: The difference between radiologic and pathologic tumor size was within ±2 mm in 40.4% cases. The mean radiologic size was 1.73 ± 1.06 cm. The mean pathologic size was 1.84 ± 1.24 cm. A paired t-test showed a significant mean difference between radiologic and pathologic measurements (0.12 ± 1.03 cm, p = 0.03). Despite the size difference, stage classification was the same in 59.9% of cases. Radiologic size overestimated stage in 14.5% of cases and underestimated stage in 25.6% of cases. The concordance rate was significantly higher for tumors ≤2 cm (pT1) (51.1%) as compared to those greater than 2 cm (≥pT2) (19.7%) (p < 0.0001). Significantly more lumpectomy specimens (47.5%) had concordance when compared to mastectomy specimens (29.8%) (p < 0.0001). Invasive ductal carcinoma had better concordance compared to other tumors (p = 0.02).

CONCLUSION: Mean pathologic tumor size was significantly different from mean radiologic tumor size. Concordance was in just over 40% of cases and the stage classification was the same in about 60% of cases only. Therefore, surgical decision of lumpectomy versus mastectomy based on radiologic tumor size may not always be accurate.}, } @article {pmid30773903, year = {2019}, author = {Shenkman, G and Bos, H and Kogan, S}, title = {Attachment avoidance and parenthood desires in gay men and lesbians and their heterosexual counterparts.}, journal = {Journal of reproductive and infant psychology}, volume = {37}, number = {4}, pages = {344-357}, doi = {10.1080/02646838.2019.1578872}, pmid = {30773903}, issn = {1469-672X}, mesh = {Adult ; Female ; *Heterosexuality ; *Homosexuality, Female ; *Homosexuality, Male ; Humans ; Male ; *Object Attachment ; *Parenting ; Regression Analysis ; }, abstract = {Objective: We explored the desire to be a parent, attachment avoidance and their associations in a sample of gay men and lesbians and their heterosexual counterparts. Background: Previous research suggested a link between minority stress and higher attachment avoidance. However, the association between attachment avoidance and parenthood desires as a function of sexual orientation was not studied. Methods: The sample was composed of 883 community-dwelling participants (51.1% women, 30.57% identified as gay men and 14.15% as lesbians) that were recruited through convenience sampling. Results: Gay men and lesbians reported less desire to be parents than their heterosexual counterparts and higher attachment avoidance. However, the association between attachment avoidance and less desire for parenthood was moderated by sexual orientation, such that the correlation between attachment avoidance and lesser desire for parenthood was only found for heterosexual men and women. Conclusion: These findings pinpoint the potential vulnerability of gay men and lesbians to develop greater attachment avoidance and the impact of sexual orientation on the association between attachment avoidance and the desire to be a parent. The moderation effect is discussed in terms of the specific reproductive alternatives available to gay men and lesbians vs. the heterosexual population.}, } @article {pmid30772490, year = {2019}, author = {Gomig, THB and Cavalli, IJ and Souza, RLR and Vieira, E and Lucena, ACR and Batista, M and Machado, KC and Marchini, FK and Marchi, FA and Lima, RS and de Andrade Urban, C and Cavalli, LR and Ribeiro, EMSF}, title = {Quantitative label-free mass spectrometry using contralateral and adjacent breast tissues reveal differentially expressed proteins and their predicted impacts on pathways and cellular functions in breast cancer.}, journal = {Journal of proteomics}, volume = {199}, number = {}, pages = {1-14}, doi = {10.1016/j.jprot.2019.02.007}, pmid = {30772490}, issn = {1876-7737}, mesh = {Breast/*cytology ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/chemistry ; Female ; Humans ; Metabolic Networks and Pathways ; Middle Aged ; Neoplasm Proteins/*analysis ; Proteome/*analysis ; Proteomics/*methods ; Tandem Mass Spectrometry/*methods ; Up-Regulation ; }, abstract = {Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. A total of 462 proteins was observed as differentially expressed (DEPs) among the groups analyzed. A high level of similarity was observed in the proteome profile of both non-tumor breast tissues and DEPs (n = 12) were mainly predicted in the RNA metabolism. The DEPs among the malignant and non-tumor breast tissues [n = 396 (PTxNCT) and n = 410 (LNxNCT)] were related to pathways of the LXR/RXR, NO, eNOS, eIF2 and sirtuins, tumor-related functions, fatty acid metabolism and oxidative stress. Remarkable similarity was observed between both malignant tissues, which the DEPs were related to metastatic capabilities. Altogether, our findings revealed differential proteomic profiles that affected cancer associated and interconnected signaling processes. Validation studies are recommended to demonstrate the potential of individual proteins and/or pathways as biological markers in breast cancer. SIGNIFICANCE: The proteomic analysis of this study revealed high similarity in the proteomic profile of the contralateral and adjacent non-tumor breast tissues. Significant differences were identified among the proteome of the malignant and non-tumor tissue groups of the same patients, providing relevant insights into the hallmarks, signaling pathways, biological functions, and interactive protein networks that act during tumorigenesis and breast cancer progression. These proteins are suggested as targets of relevant interest to be explored as potential biological markers related to tumor development and metastatic progression in the breast cancer disease.}, } @article {pmid30772465, year = {2019}, author = {Ducommun, S and Deak, M and Zeigerer, A and Göransson, O and Seitz, S and Collodet, C and Madsen, AB and Jensen, TE and Viollet, B and Foretz, M and Gut, P and Sumpton, D and Sakamoto, K}, title = {Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates.}, journal = {Cellular signalling}, volume = {57}, number = {}, pages = {45-57}, doi = {10.1016/j.cellsig.2019.02.001}, pmid = {30772465}, issn = {1873-3913}, mesh = {AMP-Activated Protein Kinases/*metabolism ; Animals ; Guanine Nucleotide Exchange Factors/*metabolism ; Hepatocytes/metabolism ; Homeostasis/genetics/physiology ; Lipid Metabolism/genetics ; Liver/*metabolism ; Mass Spectrometry/methods ; Membrane Proteins/*metabolism ; Mice, Knockout ; Muscle Proteins/*metabolism ; Phosphorylation ; Substrate Specificity ; }, abstract = {AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.}, } @article {pmid30771577, year = {2019}, author = {Liao, W and Li, C and Tang, Y and Huang, F and Kuang, H and Liang, S and Yang, Y}, title = {Aquaporin-4 antibody positive short transverse myelitis associated with breast cancer.}, journal = {Multiple sclerosis and related disorders}, volume = {30}, number = {}, pages = {119-122}, doi = {10.1016/j.msard.2019.02.011}, pmid = {30771577}, issn = {2211-0356}, mesh = {Adult ; Antibodies/*cerebrospinal fluid ; Aquaporin 4/*immunology ; Breast Neoplasms/*cerebrospinal fluid/complications/diagnostic imaging ; Carcinoma/*cerebrospinal fluid/complications/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Myelitis, Transverse/*blood/complications/diagnostic imaging ; Spinal Cord/diagnostic imaging ; }, abstract = {Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). A typical finding on spinal magnetic resonance imaging (MRI) of NMOSD is longitudinally extensive transverse myelitis (LETM). However, patients with NMOSD presenting with short-segment transverse myelitis (STM) during myelitis attacks associated with breast cancer are uncommon. We report a case of a 35-year-old woman with STM and left eye optic neuritis. The patient was positive for serum aquaporin-4 antibodies (AQP4-IgG), and a biopsy of the left breast showed invasive ductal carcinoma. The patient was diagnosed with NMOSD and breast malignancy. This is the first report of a patient with NMOSD whose spinal MRI showed STM and serum test showed that the patient's AQP4-IgG was positive and complicated by breast cancer. This case improves our understanding of the association between NMOSD and cancer and raises the question of whether it was a coincidental occurrence. It is important to search for extensive malignancies in patients presenting with atypical MRI or no reaction to traditional therapies.}, } @article {pmid30771195, year = {2019}, author = {Miyake, M and Yamada, A and Miyake, K and Endo, I}, title = {Esophageal metastasis of breast cancer during endocrine therapy for pleural dissemination 21 years after breast surgery: a case report.}, journal = {Surgical case reports}, volume = {5}, number = {1}, pages = {22}, pmid = {30771195}, issn = {2198-7793}, abstract = {BACKGROUND: The esophageal metastasis of breast cancer is rare. Moreover, it is extremely unusual for patients to experience the symptoms of esophageal metastasis during their lifetimes. We present a case of dysphagia caused by esophageal metastasis after a long interval following a primary mastectomy.

CASE PRESENTATION: A 77-year-old woman with a history of heterochronous bilateral breast cancer and under treatment for pleural dissemination recurrence originating from right breast cancer complained of dysphagia. At the age of 56, she had undergone a right radical mastectomy for right breast cancer. The histopathological findings revealed invasive ductal carcinoma, pT3N1M0, which was estrogen receptor (ER)- and progesterone receptor (PgR)-positive. At the age of 73, she underwent a second operation, a left modified radical mastectomy. The histopathological examination revealed invasive ductal carcinoma, pT1N0M0, which was negative for ER, PgR, and human epidermal growth factor receptor 2 (HER2). Four years after completion of adjuvant therapy for the left breast cancer, pleural effusion on her left side was observed and histopathological examination of a sample revealed pleural dissemination resulting from the right breast cancer. After initiation of therapy for recurrence, she developed dysphagia and, therefore, underwent an upper gastrointestinal tract endoscopic examination. The examination revealed whole circumferential stenosis and a band unstained by Lugol's solution located 30 cm from her incisors. Examination of a biopsy specimen revealed a subepithelial luminal structure and dysplastic cells. Immunostaining was positive for CK7 and negative for CK20; furthermore, the sample was ER and PgR-positive. Considering the pathological findings, the patient was diagnosed with esophageal metastasis of her right breast cancer.

CONCLUSIONS: Metastatic lesions in the esophagus are often located in the submucosa; therefore, they may not be definitively diagnosed by histopathological examination of mucosal biopsy specimens. Esophageal metastasis originating from breast cancer often occurs as a part of multiple organ metastases; however, esophageal metastasis is usually not considered a prognostic factor for patients. Therefore, treatment should be determined according to the severity of the other metastatic sites and the degree of esophageal stenosis.}, } @article {pmid30770989, year = {2019}, author = {Yan, Z and Ohuchida, K and Zheng, B and Okumura, T and Takesue, S and Nakayama, H and Iwamoto, C and Shindo, K and Moriyama, T and Nakata, K and Miyasaka, Y and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M}, title = {CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis.}, journal = {Journal of cancer research and clinical oncology}, volume = {145}, number = {5}, pages = {1147-1164}, pmid = {30770989}, issn = {1432-1335}, mesh = {Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor ; Carcinoma, Pancreatic Ductal/genetics/metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Survival ; Disease Models, Animal ; Disease Progression ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms/secondary ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/genetics/*metabolism/mortality/*pathology ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, Thrombopoietin/genetics/*metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.

METHODS: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.

RESULTS: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.

CONCLUSIONS: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.}, } @article {pmid30769363, year = {2019}, author = {Guillamat-Prats, R and Rami, M and Herzig, S and Steffens, S}, title = {Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications.}, journal = {Thrombosis and haemostasis}, volume = {119}, number = {4}, pages = {567-575}, doi = {10.1055/s-0039-1678738}, pmid = {30769363}, issn = {2567-689X}, mesh = {Adipose Tissue/metabolism ; Animals ; Arachidonic Acid/chemistry ; Atherosclerosis/*metabolism ; Bile Acids and Salts/chemistry ; Blood Glucose/metabolism ; Cardiovascular System/metabolism ; Cytokines/metabolism ; Endocannabinoids/*metabolism ; Humans ; Inflammation ; Insulin Resistance ; Ligands ; Lipid Metabolism ; Lipids/chemistry ; Liver/metabolism ; Mice ; Mice, Knockout ; Obesity, Abdominal/metabolism ; Pancreas/metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Receptors, Cannabinoid/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Risk Factors ; *Signal Transduction ; }, abstract = {Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications.}, } @article {pmid30763392, year = {2019}, author = {Lyng, FM and Traynor, D and Nguyen, TNQ and Meade, AD and Rakib, F and Al-Saady, R and Goormaghtigh, E and Al-Saad, K and Ali, MH}, title = {Discrimination of breast cancer from benign tumours using Raman spectroscopy.}, journal = {PloS one}, volume = {14}, number = {2}, pages = {e0212376}, pmid = {30763392}, issn = {1932-6203}, mesh = {Breast/metabolism/*pathology ; Breast Neoplasms/diagnosis/metabolism/*pathology ; Discriminant Analysis ; Female ; Humans ; Hyperplasia ; Principal Component Analysis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Sensitivity and Specificity ; Spectrum Analysis, Raman/*methods ; Support Vector Machine ; }, abstract = {Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million cases and 522,000 deaths in 2012. Breast cancer is diagnosed by histopathological examination of breast biopsy material but this is subjective and relies on morphological changes in the tissue. Raman spectroscopy uses incident radiation to induce vibrations in the molecules of a sample and the scattered radiation can be used to characterise the sample. This technique is rapid and non-destructive and is sensitive to subtle biochemical changes occurring at the molecular level. This allows spectral variations corresponding to disease onset to be detected. The aim of this work was to use Raman spectroscopy to discriminate between benign lesions (fibrocystic, fibroadenoma, intraductal papilloma) and cancer (invasive ductal carcinoma and lobular carcinoma) using formalin fixed paraffin preserved (FFPP) tissue. Haematoxylin and Eosin stained sections from the patient biopsies were marked by a pathologist. Raman maps were recorded from parallel unstained tissue sections. Immunohistochemical staining for estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2/neu) was performed on a further set of parallel sections. Both benign and cancer cases were positive for ER while only the cancer cases were positive for HER2. Significant spectral differences were observed between the benign and cancer cases and the benign cases could be differentiated from the cancer cases with good sensitivity and specificity. This study has shown the potential of Raman spectroscopy as an aid to histopathological diagnosis of breast cancer, in particular in the discrimination between benign and malignant tumours.}, } @article {pmid30762822, year = {2019}, author = {Louarn, N and Dauta, A and Lechapt-Zalcman, E and Kauv, P and Itti, E}, title = {Meningeal Metastasis Relapse With Focal Involvement of Cranial Bone Flap: A Case Resolved by 18F-DOPA PET/MRI.}, journal = {Clinical nuclear medicine}, volume = {44}, number = {4}, pages = {e315-e317}, doi = {10.1097/RLU.0000000000002492}, pmid = {30762822}, issn = {1536-0229}, mesh = {Breast Neoplasms/pathology ; *Dihydroxyphenylalanine ; Female ; *Fluorine Radioisotopes ; Humans ; *Magnetic Resonance Imaging ; Meningeal Neoplasms/*diagnostic imaging/*secondary ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Recurrence ; Skull/diagnostic imaging/metabolism ; }, abstract = {A 63-year-old woman was referred to our PET/MRI platform to evaluate the possible relapse of a meningeal metastasis, complicating an invasive ductal carcinoma of the left breast. This metastasis was diagnosed on a left hemiparesis and treated by surgery and radiation therapy. One year later, the same symptoms led to another brain MRI examination that found a contrast-enhanced lesion in the operating site. We decided to perform a F-DOPA PET/MRI to document this lesion, which confirmed the diagnosis of a probable relapse and revealed a focal uptake on the bone flap.}, } @article {pmid30761666, year = {2019}, author = {Yilmaz, R and Akpinar, Y and Ozyavuz, I and Önder, S and Tukenmez, M and Dursun, M}, title = {Synchronous metastatic leiomyosarcoma and primer invasive ductal carcinoma tumors in the same breast: Mammography, ultrasonography, and magnetic resonance imaging findings.}, journal = {The breast journal}, volume = {25}, number = {2}, pages = {310-311}, doi = {10.1111/tbj.13211}, pmid = {30761666}, issn = {1524-4741}, mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Leiomyosarcoma/*diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; Unilateral Breast Neoplasms/*diagnostic imaging/pathology/secondary ; }, } @article {pmid30760857, year = {2019}, author = {Alsaleem, M and Toss, MS and Joseph, C and Aleskandarany, M and Kurozumi, S and Alshankyty, I and Ogden, A and Rida, PCG and Ellis, IO and Aneja, R and Green, AR and Mongan, NP and Rakha, EA}, title = {The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {32}, number = {7}, pages = {967-976}, doi = {10.1038/s41379-019-0209-9}, pmid = {30760857}, issn = {1530-0285}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genomic Instability/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Middle Aged ; Tissue Array Analysis ; Young Adult ; }, abstract = {E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.}, } @article {pmid30747875, year = {2019}, author = {Kaundal, P and Sharma, AP and Mavuduru, R and Devana, SK and Bora, GS}, title = {Re: Long-Term Surveillance of Complex Cystic Renal Masses and Heterogeneity of Bosniak 3 LesionsD. K. Pruthi, Q. Liu, I. D. C. Kirkpatrick, J. Gelfond and D. E. Drachenberg J Urol 2018; 200: 1192-1199.}, journal = {The Journal of urology}, volume = {201}, number = {6}, pages = {1206-1207}, doi = {10.1097/JU.0000000000000143}, pmid = {30747875}, issn = {1527-3792}, mesh = {Humans ; *Kidney Diseases, Cystic ; *Kidney Neoplasms ; }, } @article {pmid30746830, year = {2019}, author = {Malkin, G and Hayat, T and Amichai-Hamburger, Y and Ben-David, BM and Regev, T and Nakash, O}, title = {How well do older adults recognise mental illness? A literature review.}, journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society}, volume = {19}, number = {5}, pages = {491-504}, doi = {10.1111/psyg.12427}, pmid = {30746830}, issn = {1479-8301}, mesh = {Aged ; *Aging ; *Health Knowledge, Attitudes, Practice ; *Health Literacy ; Humans ; *Mental Disorders ; }, abstract = {Older adults tend to underutilise mental health services. Mental health literacy plays a critical role in identifying and overcoming barriers to accessing mental health care. The ability to recognise mental illness is an essential component of mental health literacy, with important implications to whether the person will seek professional help. We conducted a review of the literature on older adults' abilities to recognise mental illness. Of the 421 papers that were retrieved in the comprehensive search in PubMed, 32 studies met inclusion criteria. Studies were heterogeneous in terms of target population and methodology, yet findings show that older adults are less likely to correctly recognise mental disorders. Cueing older participants with mental labels improved their recognition abilities. Recognition was particularly poor among immigrant and ethnic/racial older adults, likely due to linguistic and cultural barriers. Our findings demonstrate that older adults show low levels of mental illness recognition and tend to view some illnesses as normal parts of aging. Findings emphasise the need for developing educational programs tailored by the specific phenomenology, conceptualisations and cultural meanings of mental illness among older adults, with attention to informal sources of information and social networks.}, } @article {pmid30744177, year = {2019}, author = {Markovic, T and Bao, J and Maenhout, G and Ocket, I and Nauwelaers, B}, title = {An Interdigital Capacitor for Microwave Heating at 25 GHz and Wideband Dielectric Sensing of nL Volumes in Continuous Microfluidics.}, journal = {Sensors (Basel, Switzerland)}, volume = {19}, number = {3}, pages = {}, pmid = {30744177}, issn = {1424-8220}, abstract = {This paper proposes a miniature microwave-microfluidic chip based on continuous microfluidics and a miniature interdigital capacitor (IDC). The novel chip consists of three individually accessible heaters, three platinum temperature sensors and two liquid cooling and mixing zones. The IDC is designed to achieve localized, fast and uniform heating of nanoliter volumes flowing through the microfluidic channel. The heating performance of the IDC located on the novel chip was evaluated using a fluorescent dye (Rhodamine B) diluted in demineralized water on a novel microwave-optical-fluidic (MOF) measurement setup. The MOF setup allows simultaneous microwave excitation of the IDC by means of a custom-made printed circuit board (connected to microwave equipment) placed in a top stage of a microscope, manipulation of liquid flowing through the channel located over the IDC with a pump and optical inspection of the same liquid flowing over the IDC using a fast camera, a light source and the microscope. The designed IDC brings a liquid volume of around 1.2 nL from room temperature to 100 °C in 21 ms with 1.58 W at 25 GHz. Next to the heating capability, the designed IDC can dielectrically sense the flowing liquid. Liquid sensing was evaluated on different concentration of water-isopropanol mixtures, and a reflection coefficient magnitude change of 6 dB was recorded around 8.1 GHz, while the minimum of the reflection coefficient magnitude shifted in the same frequency range for 60 MHz.}, } @article {pmid30742779, year = {2019}, author = {Glantschnig, C and Koenen, M and Gil-Lozano, M and Karbiener, M and Pickrahn, I and Williams-Dautovich, J and Patel, R and Cummins, CL and Giroud, M and Hartleben, G and Vogl, E and Blüher, M and Tuckermann, J and Uhlenhaut, H and Herzig, S and Scheideler, M}, title = {A miR-29a-driven negative feedback loop regulates peripheral glucocorticoid receptor signaling.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {5}, pages = {5924-5941}, doi = {10.1096/fj.201801385RR}, pmid = {30742779}, issn = {1530-6860}, mesh = {Adipocytes/*cytology/metabolism ; Adipogenesis ; Animals ; Corticosterone/metabolism ; Feedback, Physiological ; Female ; *Gene Expression Regulation ; Glucocorticoids/*metabolism ; HEK293 Cells ; Humans ; Inflammation ; Insulin/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*metabolism ; Obesity/surgery ; Overweight/surgery ; Phenotype ; RNA, Small Interfering/metabolism ; Receptors, Glucocorticoid/metabolism ; Signal Transduction ; Stem Cells/cytology ; Transfection ; }, abstract = {The glucocorticoid receptor (GR) represents the crucial molecular mediator of key endocrine, glucocorticoid hormone-dependent regulatory circuits, including control of glucose, protein, and lipid homeostasis. Consequently, aberrant glucocorticoid signaling is linked to severe metabolic disorders, including insulin resistance, obesity, and hyperglycemia, all of which also appear upon chronic glucocorticoid therapy for the treatment of inflammatory conditions. Of note, long-term glucocorticoid exposure under these therapeutic conditions typically induces glucocorticoid resistance, requiring higher doses and consequently triggering more severe metabolic phenotypes. However, the molecular basis of acquired glucocorticoid resistance remains unknown. In a screen of differential microRNA expression during glucocorticoid-dependent adipogenic differentiation of human multipotent adipose stem cells, we identified microRNA 29a (miR-29a) as one of the most down-regulated transcripts. Overexpression of miR-29a impaired adipogenesis. We found that miR-29a represses GR in human adipogenesis by directly targeting its mRNA, and downstream analyses revealed that GR mediates most of miR-29a's anti-adipogenic effects. Conversely, miR-29a expression depends on GR activation, creating a novel miR-29-driven feedback loop. miR-29a and GR expression were inversely correlated both in murine adipose tissue and in adipose tissue samples obtained from human patients. In the latter, miR-29a levels were additionally strongly negatively correlated with body mass index and adipocyte size. Importantly, inhibition of miR-29 in mice partially rescued the down-regulation of GR during dexamethasone treatment. We discovered that, in addition to modulating GR function under physiologic conditions, pharmacologic glucocorticoid application in inflammatory disease also induced miR-29a expression, correlating with reduced GR levels. This effect was abolished in mice with impaired GR function. In summary, we uncovered a novel GR-miR-29a negative feedback loop conserved between mice and humans, in health and disease. For the first time, we elucidate a microRNA-related mechanism that might contribute to GR dysregulation and resistance in peripheral tissues.-Glantschnig, C., Koenen, M., Gil-Lozano, M., Karbiener, M., Pickrahn, I., Williams-Dautovich, J., Patel, R., Cummins, C. L., Giroud, M., Hartleben, G., Vogl, E., Blüher, M., Tuckermann, J., Uhlenhaut, H., Herzig, S., Scheideler, M. A miR-29a-driven negative feedback loop regulates peripheral glucocorticoid receptor signaling.}, } @article {pmid30738200, year = {2019}, author = {Lopez Gordo, S and Blanch Falp, J and Lopez-Gordo, E and Just Roig, E and Encinas Mendez, J and Seco Calvo, J}, title = {Influence of ductal carcinoma in situ on the outcome of invasive breast cancer. A prospective cohort study.}, journal = {International journal of surgery (London, England)}, volume = {63}, number = {}, pages = {98-106}, doi = {10.1016/j.ijsu.2019.01.016}, pmid = {30738200}, issn = {1743-9159}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/therapy ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS)-associated invasive ductal carcinoma (IDC) is present in a large number of patients with breast cancer. However, the association between these two entities has not been studied in detail. The aim of this study is to compare the clinical and histopathological factors associated to recurrence of IDC with those of DCIS-associated IDC (IDC + DCIS).

MATERIALS AND METHODS: A prospective observational longitudinal study of 464 patients was performed between 2010 and 2015. Patients with IDC and DCIS + IDC were included and analyzed.

RESULTS: IDC + DCIS was present in 243 patients (52.4%). No difference on histopathological characteristics were found, only Grade I and II of invasive component were more frequent in patients with IDC + DCIS than those with IDC (p  =  0.038). No differences on recurrence were found between the main groups (p = 0.256). For patients who received neoadjuvant chemotherapy, those with IDC + DCIS had lower response than those with IDC alone (p  =  0.014). No differences between the main groups were found on recurrence (p = 0.256). For patients who received neoadjuvant chemotherapy, recurrence was present in 19 patients (30.6%) in the IDC group in contrast to 5 (12.2%) in the IDC + DCIS group (p = 0.030). Mortality was present in 15 patients (24.2%) in the IDC group in contrast to 3 (7.3%) in the IDC + DCIS group (p = 0.027). At 7 years, 80.8% patients were alive: 71.9% from the IDC group and 92.7% from the IDC + DCIS group.

CONCLUSIONS: The presence of DCIS seems to be indicative of a benign behavior in patients who receive neoadjuvant chemotherapy. Longer DFS and higher overall survival were found in the IDC + DCIS group despite presenting with a lower response to chemotherapy. These findings help us identify patients with better prognosis in breast cancer.}, } @article {pmid30728717, year = {2019}, author = {Lee, J and Oh, M and Ko, S and Park, C and Lee, ES and Kim, HA and Jung, Y and Lee, J and , }, title = {Parity Differently Affects the Breast Cancer Specific Survival from Ductal Carcinoma In Situ to Invasive Cancer: A Registry-Based Retrospective Study from Korea.}, journal = {Breast cancer : basic and clinical research}, volume = {13}, number = {}, pages = {1178223418825134}, pmid = {30728717}, issn = {1178-2234}, abstract = {PURPOSE: Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma.

METHODS: We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC.

RESULTS: The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group (P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients (P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04).

CONCLUSIONS: Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.}, } @article {pmid30728399, year = {2019}, author = {Kaur, P and Porras, TB and Ring, A and Carpten, JD and Lang, JE}, title = {Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {1482}, pmid = {30728399}, issn = {2045-2322}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Computer Simulation ; DNA Copy Number Variations/genetics ; Databases, Genetic/*standards/*trends ; Exome/genetics ; Female ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mutation/genetics ; Precision Medicine/methods ; }, abstract = {Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor.}, } @article {pmid30725231, year = {2019}, author = {Liu, Y and Pandey, PR and Sharma, S and Xing, F and Wu, K and Chittiboyina, A and Wu, SY and Tyagi, A and Watabe, K}, title = {ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness.}, journal = {Breast cancer research and treatment}, volume = {175}, number = {1}, pages = {77-90}, pmid = {30725231}, issn = {1573-7217}, support = {R01CA205067//National Cancer Institute (US)/ ; F31 CA200286/CA/NCI NIH HHS/United States ; F31CA200286//National Cancer Institute/ ; R01CA173499//National Cancer Institute/ ; R01 CA173499/CA/NCI NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; R01CA185650//National Cancer Institute/ ; R01 CA205067/CA/NCI NIH HHS/United States ; R01 CA185650/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Proliferation ; Chalcone/analogs & derivatives/chemistry/pharmacology ; Connexin 26 ; Connexins/*genetics ; Disease Models, Animal ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Inhibitor of Differentiation Protein 2/*genetics ; Mice ; Neoplasm Staging ; Neoplastic Stem Cells/*metabolism ; Prognosis ; *Promoter Regions, Genetic ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer which could progress to or recur as invasive breast cancer. The underlying molecular mechanism of DCIS progression is yet poorly understood, and appropriate biomarkers to distinguish benign form of DCIS from potentially invasive tumor are urgently needed.

METHODS: To identify the key regulators of DCIS progression, we performed gene-expression analysis of syngeneic breast cancer cell lines MCF10A, DCIS.com, and MCF10CA and cross-referenced the targets with patient cohort data.

RESULTS: We identified ID2 as a critical gene for DCIS initiation and found that ID2 promoted DCIS formation by enhancing cancer stemness of pre-malignant cells. ID2 also plays a pivotal role in survival of the aggressive cancer cells. In addition, we identified INHBA and GJB2 as key regulators for the transition of benign DCIS to aggressive phenotype. These two genes regulate migration, colonization, and stemness of invasive cancer cells. Upregulation of ID2 and GJB2 predicts poor prognosis after breast-conserving surgery. Finally, we found a natural compound Helichrysetin as ID2 inhibitor which suppresses DCIS formation in vitro and in vivo.

CONCLUSION: Our results indicate that ID2 is a key driver of DCIS formation and therefore is considered to be a potential target for prevention of DCIS, while INHBA and GJB2 play vital roles in progression of DCIS to IDC and they may serve as potential prognosis markers.}, } @article {pmid30719718, year = {2019}, author = {Dianatinasab, M and Fararouei, M and Daneshi, N and Rezaian, S and Mohammadianpanah, M and Chaman, R and Ghiasvand, R}, title = {Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.}, journal = {International journal of cancer}, volume = {145}, number = {11}, pages = {2917-2925}, doi = {10.1002/ijc.32182}, pmid = {30719718}, issn = {1097-0215}, mesh = {Abortion, Spontaneous/epidemiology ; Adult ; Breast Feeding/statistics & numerical data ; Breast Neoplasms/*epidemiology/etiology ; Carcinoma, Ductal, Breast/*epidemiology/etiology ; Carcinoma, Lobular/*epidemiology/etiology ; Case-Control Studies ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Iran ; Middle Aged ; Risk Factors ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.}, } @article {pmid30713371, year = {2019}, author = {Abubakar, ZA and Akepati, NKR and Bikkina, P}, title = {Correlation of Maximum Standardized Uptake Values in 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography Scan with Immunohistochemistry and Other Prognostic Factors in Breast Cancer.}, journal = {Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India}, volume = {34}, number = {1}, pages = {10-13}, pmid = {30713371}, issn = {0972-3919}, abstract = {OBJECTIVES: The objective of this study was to correlate maximum standardized uptake value (SUVmax) with different immunohistochemical subtypes of breast cancer and other prognostic factors in breast cancer.

SUBJECTS AND METHODS: This was a retrospective study including 219 consecutive patients undergoing whole-body fluorodeoxyglucose positron emission tomography/computed tomography scan for the staging of breast cancer. Out of 219 patients, two were male and 217 were female; age ranged from 26 to 85 years with mean age of 54 years. On histopathological examination (HPE), 197 patients were of invasive ductal carcinoma type and two of lobular type. Histopathological grades, immunohistochemistry (IHC) types, and ki-67 values were compared with SUVmax values.

RESULTS: The mean SUVmax of the population was 11.39 (±6.05). The mean SUVmax in different HPE grades was Grade 1 = 6.81 ± 5.6, Grade 2 = 11.4 ± 6.12, and Grade 3 = 13.14 ± 5. The mean SUVmax values in different IHC types were Luminal A = 7.75 ± 4.2, Luminal B = 10.01 ± 5.3, triple negative = 15.26 ± 5.6, and HER2 enriched = 11.27 ± 5.2. The mean SUVmax in high ki-67 patients was 11.97 ± 5.85 compared with 7.25 ± 3.43 patients with low ki-67. Univariate analysis showed significant difference in SUVmax in patients with different grades (P = 0.013), hormone receptor positivity (P ≤ 0.001), ki-67 (P < 0.001), and axillary lymph node positivity (P ≤ 0.001). In multivariate regression analysis, there was significantly higher SUVmax value in triple-negative patients after correcting for tumor size, ki-67 value, axillary lymph node status, and grade of tumor.

CONCLUSION: High SUVmax values were noted in high-grade, high ki-67, triple-negative, and axillary lymph node positive tumors.}, } @article {pmid30712460, year = {2020}, author = {Song, G and He, L and Yang, X and Yang, Y and Cai, X and Liu, K and Feng, G}, title = {Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.}, journal = {The Journal of international medical research}, volume = {48}, number = {1}, pages = {300060518815364}, pmid = {30712460}, issn = {1473-2300}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cluster Analysis ; Databases, Genetic ; *Disease Progression ; Down-Regulation/genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics/metabolism ; Reproducibility of Results ; Signal Transduction/genetics ; Up-Regulation/genetics ; }, abstract = {OBJECTIVE: It has been reported that 80% of all breast carcinoma cases are invasive ductal carcinoma (IDC), and 45% to 78% of invasive breast carcinoma cases are associated with ductal carcinoma in situ (DCIS). Therefore, it is important to gain insights into transcriptome changes that occur during DCIS progression to IDC.

METHODS: We downloaded Gene Expression Omnibus databases GSE21422 and GSE3893, and performed differentially expressed gene (DEG) analysis and cluster analysis, followed by pathway enrichment analysis and Oncomine analysis.

RESULTS: Twenty-six conserved DEGs were identified in both GSE21422 and GSE3893. These genes are mainly enriched in intermediate filament-based processes, immune responses, Staphylococcus aureus infection response, and phagosomes. Among them, FCGR2A, HLA-DRA, C3AR1, and FYB were reported to be involved in DCIS progression to IDC. High expression of HLA-DRA, C3AR1, and FYB in different types of breast cancer was validated using different Oncomine datasets. Moreover, elevated HLA-DRA and FYB levels were associated with breast cancer recurrence. Importantly, the overexpression of FYB was correlated with breast cancer metastasis.

CONCLUSIONS: This study revealed the molecular characteristics associated with progression from DCIS to IDC. It also identified potential biomarkers for DCIS progression to IDC, which will aid breast cancer diagnosis and prevention.}, } @article {pmid30697055, year = {2019}, author = {Chen, DD and Ji, JA and Yan, HC and Huang, GH and Fang, XJ}, title = {Effect of CD44st and HER2 expression on the postoperative prognosis of breast cancer patients.}, journal = {OncoTargets and therapy}, volume = {12}, number = {}, pages = {577-585}, pmid = {30697055}, issn = {1178-6930}, abstract = {OBJECTIVE: CD44st is a member of the CD44 family; abnormal expression of some CD44 isoforms are closely associated with axillary lymph node metastasis, cancer progression, and patients' prognosis. The objective of this study is to investigate the correlation between the expression of CD44st and HER2 in breast cancer and the effect on patients' prognosis.

METHODS: Primers were designed to target the CD44st mRNA (Gene Bank No FJ216964) which has been newly identified in a drug-resistant breast cancer cell line. The expression of CD44st and HER2 mRNA and proteins in cancerous and paracancerous tissue of postoperative breast cancer patients was detected and compared. Tissue samples were obtained from 102 cases of invasive ductal carcinoma, 19 cases of intraductal carcinoma, and 11 cases of medullary carcinoma. The correlation between CD44st and HER2 expression and clinical pathological features was examined.

RESULTS: The expression rate of CD44st mRNA and protein in breast cancer tissue was 64.4% (85/132), while HER2 mRNA and protein was expressed in 22.0% (29/106) of the samples. The expression of CD44st and HER2 were low in paracancerous tissue. In breast cancer tissue, the expression rate of HER2 mRNA and protein in the CD44st-positive group was 28.2% (24/85), and 10.6% (5/47) in the CD44st-negative group. This difference was statistically significant (P=0.015). Sequencing analysis showed that the amplified CD44st gene in this study was the same as that which was previously discovered in the drug-resistant breast cancer cell line. A linear correlation was found between the expression of CD44st and HER2 (r=0.972, r2=0.945, F=2,213.51, P<0.001). The expression of CD44st and HER2 was also closely associated with luminal cancer subtypes, lymph node metastasis, and TNM stage (P<0.05), but not associated with age, pathological type, or tumor size (P>0.05). The median overall survival in the CD44st high-expression group was 51.85 months (95% CI: 48.48-55.22), which was significantly shorter than that in the CD44st low-expression group (57.61 months; 95% CI: 55.54-59.68, P=0.032).

CONCLUSION: CD44st is closely related to the expression of HER2. The expression of CD44st affects patient prognosis and is associated with lymph node metastasis, TNM staging, and molecular subtyping.}, } @article {pmid30694572, year = {2019}, author = {Cui, Y and Song, M and Kim, SY}, title = {Prognostic significance of fatty acid binding protein-4 in the invasive ductal carcinoma of the breast.}, journal = {Pathology international}, volume = {69}, number = {2}, pages = {68-75}, doi = {10.1111/pin.12756}, pmid = {30694572}, issn = {1440-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Disease-Free Survival ; Fatty Acid-Binding Proteins/*biosynthesis ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {We conducted this study to identify clinico-pathologic and prognostic factors that are associated with fatty acid binding protein-4 (FABP4) and to discuss its therapeutic potentials in patients with breast cancer (BC). In a total of 75 patients with an established diagnosis of invasive ductal carcinoma of the breast, we performed a retrospective analysis of the medical records and analyzed their immunohistochemical findings. Following evaluation of baseline and clinico-pathological characteristics such as the age, immunohistochemical expressions of FABP4, TNM stage, tumor grade, lymphatic and perineural invasion, estrogen receptor (ER) and progesterone receptor (PR), disease-free survival (DFS), overall survival (OS), recurrence and death, we analyzed correlations of the expression of FABP4 with clinico-pathologic and prognostic factors. Our results showed that tumor grade and recurrence had a significant correlation with the expression of FABP4 (P = 0.002 and 0.049, respectively). Moreover, we also found that the DFS had a significant correlation with the expression of FABP4 (P = 0.049). It can therefore be concluded that the expression of FABP4 might have a prognostic value in patients with BC. But further studies are warranted to establish its potentials as a prognostic indicator.}, } @article {pmid30693115, year = {2018}, author = {Barghouthi, N and Turner, J and Perini, J}, title = {Breast Cancer Development in a Transgender Male Receiving Testosterone Therapy.}, journal = {Case reports in endocrinology}, volume = {2018}, number = {}, pages = {3652602}, pmid = {30693115}, issn = {2090-6501}, abstract = {CONTEXT: To describe a case of invasive ductal carcinoma of the breast in a transgender male receiving testosterone therapy for gender-affirming treatment.

CASE DESCRIPTION: A 28-year-old transgender male receiving intramuscular testosterone was found to have a breast mass on ultrasound after self-exam revealed a palpable breast lump. Ultrasound-guided breast biopsy revealed estrogen receptor/progesterone receptor (ER/PR) negative, human epidermal growth factor receptor-2 (HER-2) positive, invasive ductal carcinoma of the left breast. He underwent neoadjuvant and adjuvant chemotherapy along with bilateral mastectomy. At patient request, his testosterone injections were permanently discontinued.

CONCLUSION: Fewer than 20 cases of breast cancer in transgender male patients have been reported in medical literature. While studies have shown increased risk of breast cancer in postmenopausal women with higher testosterone levels, data regarding premenopausal women is conflicting and little is known about breast cancer risk in transgender individuals receiving gender-affirming hormone therapy (GAHT), with inconclusive results regarding correlation between testosterone therapy and breast cancer. More research is required to evaluate whether a possible increased risk of breast cancer exists for transgender men receiving gender-affirming therapy.}, } @article {pmid30692446, year = {2018}, author = {Nakayasu, Y and Shiozawa, S and Usui, T and Kuhara, K and Kono, T and Shimojima, Y and Tsuchiya, A and Miyauchi, T and Asaka, S and Yamaguchi, K and Yokomizo, H and Shimakawa, T and Naritaka, Y}, title = {[A Case of Borderline Resectable Pancreatic Head Cancer Treated by Curative Resection after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {2306-2308}, pmid = {30692446}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Neoadjuvant Therapy ; *Pancreatic Neoplasms/drug therapy/surgery ; *Pancreaticoduodenectomy ; Tomography, X-Ray Computed ; }, abstract = {A 77-year-old woman with back and epigastric pains was diagnosed with pancreatic head cancer according to the result of contrast computed tomography, which showed a 25mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was borderline resectable(BR)pancreatic head cancer, cT3, N0, M0, cStage ⅡA. The patient was treated with gemcitabine plus nab-paclitaxel therapy. She developed Grade 3 neutropenia, and the dose was adjusted in order to continue chemotherapy. The size of the tumor had reduced to 15mm after 6 courses of the therapy, and the infiltration into the superior mesenteric plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreatoduodenectomy and D2 lymph node dissection. The histopathological findings were invasive ductal carcinoma with R0 radical resection. The efficacy of preoperative adjuvant chemotherapy for BR pancreatic cancer has not been established yet, but improving the R0 resection rate with preoperative chemotherapy may contribute to an improvement in the outcome of pancreatic cancer.}, } @article {pmid30692436, year = {2018}, author = {Kodera, A and Inoue, H and Ogura, K and Sakaguchi, S and Yukawa, H and Matsuoka, A and Tanaka, N and Kinoshita, J and Yoshimatsu, K and Naritaka, Y and Hirano, A}, title = {[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {2276-2278}, pmid = {30692436}, issn = {0385-0684}, mesh = {Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration & dosage ; *Breast Neoplasms/complications/drug therapy ; *Deglutition Disorders/drug therapy/etiology ; Female ; Humans ; Lymph Nodes ; Paclitaxel/administration & dosage ; Quality of Life ; }, abstract = {A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.}, } @article {pmid30692393, year = {2018}, author = {Sakurai, K and Fujisaki, S and Kubota, H and Suzuki, Y and Adachi, K and Suzuki, S and Hirano, T and Tomita, R}, title = {[Neuroendocrine Carcinoma of the Breast Encountered in the General Hospital without the Breast Department-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {1904-1906}, pmid = {30692393}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/diagnosis/surgery ; *Carcinoma, Neuroendocrine/diagnosis/surgery ; Female ; Hospitals, General ; Humans ; Mammography ; Mastectomy ; }, abstract = {Neuroendocrine carcinoma(NEC)is a rare disease. We report a case of NEC encountered in the general hospital without a breast department. The patient was a 69-year-old woman. She had received breast cancer screening and a mass on her left breast was found. Mammography revealed an ill-defined mass. Ultrasonography showed a low echoic mass, 11mm in diameter, on the A area of her left breast. A core needle biopsy of the breast tumor(A area)led to a diagnosis of an invasive ductal carcinoma, positive for estrogen receptor and progesterone receptor, but negative for HER2/neu. The Ki-67 positive cell index was 5%. We then examined her whole body and diagnosed her with T1N0M0, Stage Ⅰ. She underwent muscle-preserving mastectomy plus sentinel lymph node biopsy. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma(NEC), positive for estrogen receptor and progesterone receptor, but negative for HER2/neu. The Ki-67 positive cell index was 5%. The surgical margins were negative, and no metastasis was found in the sentinel lymph node. She was administered endocrine therapy as adjuvant therapy. Two years postoperatively, she was well without metastases.}, } @article {pmid30692379, year = {2018}, author = {Matsuoka, A and Inoue, H and Ogura, K and Hattori, A and Yukawa, H and Sakaguchi, S and Tanaka, N and Kodera, A and Kamimura, M and Naritaka, Y and Hirano, A}, title = {[HER2-Positive Breast Cancer with Severe Infusion Reaction to Pertuzumab plus Trastuzumab-A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {1863-1865}, pmid = {30692379}, issn = {0385-0684}, mesh = {*Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy ; Female ; Humans ; Middle Aged ; *Receptor, ErbB-2/analysis ; Taxoids ; Trastuzumab/administration & dosage ; }, abstract = {A 64-year-old woman detected a tumor in her left breast in July 2015, and the tumor became exposed and ulcerated in January 2016. Subsequently, the tumor began to bleed, and the patient was admitted to our hospital on an emergency basis in March 2016. A CT scan revealed the presence of a giant tumor in the left breast, accompanied by chest wall infiltration, left axillary lymph node metastasis, and multiple liver and bone metastases. Following needle biopsy, the specimen was diagnosed as Luminal-HER2-type invasive ductal carcinoma, and pertuzumab plus trastuzumab plus docetaxel was administered. Upon administration of 2/3 of the pertuzumab, the patient developed chills. Therefore, the administration rate was reduced; however, the patient experienced palpitations, nausea, tachycardia, and decreased blood pressure at the end of the administration. Pertuzumab was temporarily discontinued, a replenisher was infused, and the symptoms improved within approximately 20 minutes. However, the patient again experienced chills, tachycardia, and decreased blood pressure immediately after reinitiating trastuzumab administration and complained of strong pain at the tumor site. Continuation of chemotherapy was deemed dangerous, and administration was discontinued. It has been reported that infusion reactions to trastuzumab are associated with clinical stage. In this case, the symptoms of the infusion reaction were severe because of the large tumor volume. It is necessary to consider administration of premedication and the administration time of anti-HER2 drugs in cases with high tumor burden such as the current case.}, } @article {pmid30692378, year = {2018}, author = {Endo, M and Nagahashi, M and Tsuchida, J and Moro, K and Niwano, T and Yamaura, K and Toshikawa, C and Hasegawa, M and Ikarashi, M and Nakajima, M and Koyama, Y and Kobayashi, T and Sakata, J and Kameyama, H and Wakai, T}, title = {[A Case of Breast Cancer with Metastatic Nodules in Additionally Resected Specimens].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {1860-1862}, pmid = {30692378}, issn = {0385-0684}, mesh = {Aged ; *Breast Neoplasms/diagnosis/surgery ; *Carcinoma, Ductal, Breast/diagnosis/surgery ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/surgery ; Female ; Humans ; Mastectomy ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; }, abstract = {A 68-year-old woman who had leftbreastcancer (cT2N0M0, cStage ⅡA)underwentbreast -conserving therapy and sentinel lymph node biopsy. Pathological diagnosis of the resected specimen revealed a 60mm cancer lesion including a 50 mm invasive ductal carcinoma with surrounding ductal carcinoma in situ, although the pre-operative MRI suggested a 30mm invasive cancer. The surgical margin was positive with the exposure of ductal carcinoma in situ. Additional resection was performed with a resection margin of 20mm from the head-side stump of the previous surgery. Pathological diagnosis of the additionally resected specimen revealed a 6mm invasive carcinoma with its exposure on the surface of the specimen around the new surgical stump distant from the initial surgical margin, where no remnant cancer was noted. She underwent left mastectomy. Pathological diagnosis further revealed 7mm and 2mm invasive carcinomas in the remnant breast. The preoperative imaging was reviewed retrospectively, and it was found that identifying the nodules in the remnant breast was quite difficult based on the images, including MRI. We report a case of breast cancer with metastatic nodules in additionally resected specimens.}, } @article {pmid30692372, year = {2018}, author = {Asano, Y and Kashiwagi, S and Goto, W and Takada, K and Ishihara, S and Tauchi, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Invasive Ductal Carcinoma with Paget's Disease of the Breast].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {13}, pages = {1842-1844}, pmid = {30692372}, issn = {0385-0684}, mesh = {*Breast Neoplasms/diagnosis/surgery ; *Carcinoma, Ductal, Breast/diagnosis/surgery ; Female ; Humans ; Mammography ; Middle Aged ; Nipples ; *Paget's Disease, Mammary/diagnostic imaging/surgery ; }, abstract = {Paget's disease of the breast is usually localized in the nipple epidermis and lactiferous duct located near the nipple. Here, we report a rare case of synchronous breast carcinoma with Paget's disease and invasive ductal carcinoma. A 50-year-old woman was admitted to our hospital because of abnormalities in screening mammography findings. Ultrasonography(US) findings showed a 2.4×1.3×1.6 cm sized hypoechoic lesion in a region of the left mammary gland. Computed tomography (CT)findings did not reveal distant metastasis. Magnetic resonance imaging(MRI)revealed an approximately 2.2 cm sized irregular tumor. The pretreatment diagnosis was left non-invasive ductal carcinoma(cTisN0M0, Stage 0), and surgery was performed. The tumor was found in the range of 40.2×15.0 mm, many of which were breast ductal growth. An infiltrated image was confirmed at multiple sites, but the maximum size was 2.5×1.5 mm. Pathological findings of the main lesion revealed papillotubular carcinoma. Agglomeration of heterotypic cells with abundant cytoplasm was observed in the epidermis of the papilla. The final diagnosis was invasive breast cancer(pT1aN3M0, Stage Ⅲc, Luminal HER2)coexisting with Paget's disease.}, } @article {pmid30689164, year = {2019}, author = {da Silva Filho, AF and Vieira-de-Mello, GS and Dos Santos, PB and de Melo Rêgo, MJB and Ribeiro-Silva, A and Beltrão, EIC}, title = {N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.}, journal = {Pathology oncology research : POR}, volume = {25}, number = {2}, pages = {759-768}, pmid = {30689164}, issn = {1532-2807}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/enzymology/*pathology ; Female ; Humans ; Middle Aged ; N-Acetylglucosaminyltransferases/analysis/*metabolism ; }, abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.}, } @article {pmid30686731, year = {2019}, author = {Gest, R and Cayet, S and Arbion, F and Vildé, A and Body, G and Ouldamer, L}, title = {[Predictive factors of concordance (5mm threshold) between MRI and histological sizes of invasive lobular breast cancer].}, journal = {Gynecologie, obstetrique, fertilite & senologie}, volume = {47}, number = {3}, pages = {291-296}, doi = {10.1016/j.gofs.2019.01.004}, pmid = {30686731}, issn = {2468-7189}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Carcinoma, Lobular/diagnostic imaging/*pathology ; Female ; Hospitals, University ; Humans ; *Magnetic Resonance Imaging ; Menopause ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: The aim of this study was to search for predictive factors of concordance between MRI and histological sizes for invasive lobular breast cancer.

MATERIAL AND METHODS: All women managed for an invasive lobular breast cancer (pure or associated to a component of invasive ductal carcinoma) between 1st january 2007 and 31th december 2016 were included to the study. Univariable and multivariable analysis were performed to determine clinical or histological predictive factors of concordance between MRI and histological sizes for invasive lobular breast cancer (threshold 5mm).

RESULTS: During the study period 384 women were managed in our center for an invasive lobular carcinoma. We had access to the breast MRI of 246 of them. For a concordance witha threshold of 5mm, significant factors in univariate analysis were: menopausal status (OR 1.93[1.01-3.71], P=0.04), histological size (OR 0.97 [0.96-0.99], P<0.0001), lthe size of associated in situ component (OR 0.74 [0.32-1.71], P=0.01), multifocality (OR 0.56 [0.33-0.95] P=0.03) and the histological isolated invasive lobular carcinoma versus mixed ((OR 2.64 [1.01-6.91], P=0.03). In multivariate analysis, menopausal status, histological size and the histological isolated invasive lobular carcinoma versus mixed, were considered as independent predictive factors.

CONCLUSION: This work identified independent predictive factors of concordance between MRI and histological sizes for invasive lobular breast cancer (threshold 5mm).}, } @article {pmid30685946, year = {2019}, author = {Ahn, SJ and Song, SY and Park, HS and Park, SH and Lew, DH and Roh, TS and Lee, DW}, title = {Early experiences with robot-assisted prosthetic breast reconstruction.}, journal = {Archives of plastic surgery}, volume = {46}, number = {1}, pages = {79-83}, pmid = {30685946}, issn = {2234-6163}, abstract = {Robotic surgery facilitates surgical procedures by employing flexible arms with multiple degrees of freedom and providing high-quality 3-dimensional imaging. Robot-assisted nipplesparing mastectomy with immediate reconstruction is currently performed to avoid breast scars. Four patients with invasive ductal carcinoma underwent robot-assisted nipple-sparing mastectomy and immediate robot-assisted expander insertion. Through a 6-cm incision along the anterior axillary line, sentinel lymph node biopsy and nipple-sparing mastectomy were performed by oncologic surgeons. The pectoralis major muscle was elevated, an acellular dermal matrix (ADM) sling was created with robotic assistance, and an expander was inserted into the subpectoral, sub-ADM pocket. No patients had major complications such as hematoma, seroma, infection, capsular contracture, or nipple-areolar necrosis. The mean operation time for expander insertion was 1 hour and 20 minutes, and it became shorter with more experience. The first patient completed 2-stage prosthetic reconstruction and was highly satisfied with the unnoticeable scar and symmetric reconstruction. We describe several cases of immediate robot-assisted prosthetic breast reconstruction. This procedure is a feasible surgical option for patients who want to conceal surgical scars.}, } @article {pmid30679820, year = {2019}, author = {Kim, ES and Liang, JG and Wang, C and Cho, MY and Oh, JM and Kim, NY}, title = {Inter-digital capacitors with aerosol-deposited high-K dielectric layer for highest capacitance value in capacitive super-sensing applications.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {680}, pmid = {30679820}, issn = {2045-2322}, abstract = {Inter-digital capacitors (IDCs) with aerosol-deposition (AD) high-k dielectric layer were compared via simulation and measurements of bare IDCs and AD IDCs at room temperature and subjected to a post-annealing process for realizing capacitive super-sensing applications. IDCs with thin AD films can provide higher capacitive intensity and improvements for other dielectric performances. Therefore, IDC patterns with AD high-k dielectric layers were fabricated by varying the finger widths and gap. Moreover, we analyzed the layer microstructure design patterns using simulations and experiments with AD BaTiO3 as-deposited IDCs and IDCs subjected to annealing at 500 °C. These three different IDCs were measured using an impedance analyzer; furthermore, the AD BaTiO3 films were evaluated using X-ray diffraction, atomic force microscopy, and traveling electron microscopy. The results for the IDCs with the AD BaTiO3 film show the highest capacitance when compared with other thin layer capacitors, which is expected to be useful in realizing super-sensing applications in the future.}, } @article {pmid30679228, year = {2019}, author = {Jalali, U and Dhebri, A and Karip, E and Hunt, R}, title = {Ectopic breast carcinoma presenting as sebaceous cyst left axilla.}, journal = {BMJ case reports}, volume = {12}, number = {1}, pages = {}, pmid = {30679228}, issn = {1757-790X}, mesh = {Adult ; Antineoplastic Agents, Hormonal/adverse effects ; Axilla ; Breast Neoplasms/diagnostic imaging/drug therapy/*pathology/radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*pathology/radiotherapy ; Diagnosis, Differential ; Epidermal Cyst/diagnosis ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Sentinel Lymph Node Biopsy ; Tamoxifen/adverse effects ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {A 43-year-old woman with a positive family history of breast cancer presented with a painless lump in her left axilla for 2 years. Clinical diagnosis was a left axillary sebaceous cyst as the lump was inseparable from the skin. The lesion was excised under local anaesthesia and reported as breast tissue widely infiltrated by an invasive ductal carcinoma (grade 2). The malignancy was not involving the epidermis but <1 mm away from deeper margins. Re-excision of the deeper tissue with an axillary sentinel lymph nodes biopsy was performed and deep margins were reported to be tumour-free with no nodal involvement.}, } @article {pmid30675447, year = {2018}, author = {Nguyen, QD and Randall, JW and Harmon, TS and Robinson, AS and Cotes, C and Lee, AE and Mahon, BH and Sadruddin, S}, title = {Detection of a Mammographically Occult Breast Cancer with a Challenging Clinical History.}, journal = {Cureus}, volume = {10}, number = {11}, pages = {e3594}, pmid = {30675447}, issn = {2168-8184}, abstract = {Screening mammography has helped to identify countless incidences of breast cancer since its adoption in the 1960s. Over time, the screening guidelines and techniques have been refined to better detect malignancies and to avoid false positive results. However, weaknesses remain in mammography and represent an opportunity for improvement. The interference of natural breast tissue and glands can obscure the presence of occult breast malignancies. Additionally, the inability to differentiate breast tissue on the basis of depth, and the compounding of breast densities that occurs as a consequence of two-dimensional imaging, are setbacks when it comes to relying on mammography. User error and bias can also misguide the proper detection of underlying cancers during the radiological interpretation process. The following case represents a combination of these factors and others that culminated in a missed diagnosis of invasive ductal carcinoma in a young woman suffering from mastitis of the contralateral breast.}, } @article {pmid30675245, year = {2019}, author = {Hong, J and Kim, Y and Cho, J and Lim, SW and Park, SE and Kim, HK and Lee, H and Cho, SY and Kim, JY and Ahn, JS and Im, YH and Park, YH}, title = {Clinical features and prognosis of breast cancer with gastric metastasis.}, journal = {Oncology letters}, volume = {17}, number = {2}, pages = {1833-1841}, pmid = {30675245}, issn = {1792-1074}, abstract = {Breast cancer rarely metastasizes to the gastrointestinal tract, including the stomach. Due to the rarity of this metastasis, it is occasionally confused with a primary stomach malignancy. However, discriminating characteristic features with clinical implications may exist. The aim of the current study was to analyze the clinical features and prognosis of breast cancer with gastric metastasis. Between January 1994 and October 2016, 13 patients at Samsung Medical Center (Seoul, Korea) were clinically or pathologically determined to have breast cancer with gastric metastasis. The present study retrospectively collected clinicopathological data from the electronic medical records of these 13 female patients. At breast cancer diagnosis, the median patient age was 45 years. A total of 7 patients (53.8%) presented with invasive lobular carcinoma (ILC) and 6 (46.2%) with invasive ductal carcinoma. Of the 13 patients, 11 were stage I-III at initial breast cancer diagnosis and underwent surgery. Positivity of breast cancer tissue samples for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) was 92.3, 76.9 and 0%, respectively. Positivity of gastric metastasis lesions, based on immunohistochemistry results, was 81.8, 50 and 0% for ER, PR and HER2, respectively. The stomach was the location of the first metastatic lesion in 6 out of the 11 patients (54.5%) with de novo stage I-III cancer. The median time interval from initial breast cancer diagnosis to stomach metastasis was 77.5 months. The 3-year survival rate was 79.1%, and the estimated mean survival time was 35.1 months. Breast cancer with gastric metastasis is rare, and due to this fact, a thorough pathological review and greater clinical suspicion are required in these cases.}, } @article {pmid30675210, year = {2019}, author = {Smalley, T and Islam, SMA and Apostolatos, C and Apostolatos, A and Acevedo-Duncan, M}, title = {Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes.}, journal = {Oncology letters}, volume = {17}, number = {2}, pages = {1537-1546}, pmid = {30675210}, issn = {1792-1074}, abstract = {It is estimated that breast cancer will be the second leading cause of cancer-associated mortality in women in 2018. Previous research has demonstrated that the atypical protein kinase C-ζ (PKC-ζ) is a component of numerous dysregulated pathways in breast cancer, including cellular proliferation, survival, and cell cycle upregulation. The present study investigated the PKC-ζ protein in breast tissue to evaluate its potential as a biomarker for breast cancer invasion, and demonstrated that an overexpression of PKC-ζ protein can be indicative of carcinogenesis. The present study analyzed the expression of PKC-ζ in individuals with no tumor complications and malignant female human breast tissue samples (lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ and invasive ductal carcinoma) with the use of western blot analysis, immunohistochemistry and statistical analysis (83 samples). The present study also evaluated the invasive behavior of MDA-MB-231 breast cancer cells following the knockdown of PKC-ζ with a Transwell invasion assay and an immunofluorescent probe for filamentous actin (F-actin) organization. The data demonstrated that PKC-ζ expression was identified to be higher in invading tissues when compared with non-invading tissues. The results also suggest that PKC-ζ is more abundant in ductal tissues when compared with lobular tissues. In addition, the protein studies also suggest that PKC-ζ is a component for invasive behavior through the Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) pathway, and PKC-ζ is required for the F-actin reorganization in invasive cells. Therefore, PKC-ζ should be considered to be a biomarker in the development of breast cancer as well as an indicator of invading tumor cells.}, } @article {pmid30675127, year = {2019}, author = {Aman, NA and Doukoure, B and Koffi, KD and Koui, BS and Traore, ZC and Kouyate, M and Effi, AB}, title = {HER2 overexpression and correlation with other significant clinicopathologic parameters in Ivorian breast cancer women.}, journal = {BMC clinical pathology}, volume = {19}, number = {}, pages = {1}, pmid = {30675127}, issn = {1472-6890}, abstract = {BACKGROUND: The overexpression of HER2 is associated with worse prognosis of breast cancer which responds favourably to anti-HER2 therapy. The objective of this study was to determine the frequency of HER2 and its association with clinicopathologic factors in breast cancer in Ivory Coast.

METHODS: The study included 608 patients who were histologically diagnosed with invasive primary breast carcinoma. The immunohistochemistry testing for ER, PR, and HER2 was performed on the formalin fixed paraffin-embedded blocks of breast tissue of these patients. The analysis of variance and the Chi-Square Test were used to examine the association of the HER2 status with clinicopathologic prognostic features.

RESULTS: The average age of patients was 47 ± 11 years. Among 608 patients, 355 (58.4%) were premenopausal. Invasive ductal carcinoma of no specific type (511 cases, 84.1%) was the most frequent histologic type. Grade II tumors were 59.8%. The positivity of ER, PR, and ER/PR was 334 cases (54.9%), 252 cases (41.4%), and 356 cases (58.5%), respectively. HER2 was overexpressed in 105 cases (17.3%). The overexpression of HER2 was significantly correlated with Nottingham grade (p = 0.007). No association was observed between HER2 expression and age (p = 0.568), menopausal status (p = 0.929), histologic type (p = 0.666), ER (p = 0.137), PR (p = 0.396), and ER/PR (p = 0.134).

CONCLUSION: Breast cancer occurs in young women. HER2 status is closely related to Nottingham grade. The immunohistochemical analysis of HER2 has prognostic and therapeutic implications, and thus, contributing to efficient clinical management of patients.}, } @article {pmid30673339, year = {2019}, author = {Fujii, MH and Herschorn, SD and Sowden, M and Hotaling, EL and Vacek, PM and Weaver, DL and Sprague, BL}, title = {Detection Rates for Benign and Malignant Diagnoses on Breast Cancer Screening With Digital Breast Tomosynthesis in a Statewide Mammography Registry Study.}, journal = {AJR. American journal of roentgenology}, volume = {212}, number = {3}, pages = {706-711}, pmid = {30673339}, issn = {1546-3141}, support = {P01 CA154292/CA/NCI NIH HHS/United States ; R03 CA223725/CA/NCI NIH HHS/United States ; U54 CA163303/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/epidemiology ; Diagnosis, Differential ; Early Detection of Cancer ; Female ; Humans ; Mammography ; Mass Screening/*methods ; Middle Aged ; Radiographic Image Enhancement ; Registries ; Vermont/epidemiology ; }, abstract = {OBJECTIVE: The objective of our study was to determine whether detection rates of specific benign and malignant diagnoses differ for breast cancer screening with digital breast tomosynthesis (DBT) versus full-field digital mammography (FFDM) alone.

MATERIALS AND METHODS: We analyzed observational data from the Vermont Breast Cancer Surveillance System, including 86,349 DBT screening examinations and 97,378 FFDM screening examinations performed at eight radiology facilities in Vermont that adopted DBT screening during 2012-2016. We determined the most severe diagnosis made within 6 months after positive screening examinations. Multivariable-adjusted logistic regression was used to compare detection rates for specific diagnoses on DBT versus FFDM.

RESULTS: Compared with FFDM, DBT had a lower recall rate (adjusted odds ratio [OR], 0.81; 95% CI, 0.77-0.85) but comparable biopsy rate (OR = 1.05; 95% CI, 0.93-1.17), benign biopsy rate (OR = 1.12; 95% CI, 0.97-1.29), and cancer detection rate (OR = 0.94; 95% CI, 0.78-1.14). Among benign diagnoses, DBT and FFDM had comparable detection rates for nonproliferative lesions (OR = 1.19; 95% CI, 0.92-1.53), fibroepithelial proliferations (OR = 1.24; 95% CI, 0.85-1.81), proliferative lesions without atypia (OR = 1.13; 95% CI, 0.90-1.42), atypical lesions (OR = 0.77; 95% CI, 0.43-1.38), and lobular carcinoma in situ (LCIS) (OR = 0.92; 95% CI, 0.53-1.61). Among malignant diagnoses, DBT and FFDM had comparable detection rates for ductal carcinoma in situ (OR = 1.05; 95% CI, 0.70-1.57) and invasive breast cancer (OR = 0.92; 95% CI, 0.74-1.13), with no statistically significant differences in detection of invasive ductal carcinoma (OR = 0.83; 95% CI, 0.66-1.06), invasive lobular carcinoma (OR = 1.11; 95% CI, 0.59-2.07), or invasive mixed ductal-lobular carcinoma (OR = 1.49; 95% CI, 0.65-3.39).

CONCLUSION: Compared with FFDM, breast cancer screening with DBT has a lower recall rate while detecting a similar distribution of benign and malignant diagnoses.}, } @article {pmid30670771, year = {2019}, author = {Hao, S and Zhao, YY and Peng, JJ and Ren, F and Yang, WT and Yu, KD and Shao, ZM}, title = {Invasive micropapillary carcinoma of the breast had no difference in prognosis compared with invasive ductal carcinoma: a propensity-matched analysis.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {286}, pmid = {30670771}, issn = {2045-2322}, mesh = {Adult ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Papillary/mortality/*pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Propensity Score ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare histopathological variant of breast carcinoma that is usually associated with poor clinical characteristics. Whether IMPC has worse prognosis than invasive ductal carcinoma (IDC) is controversial. This retrospective study examined the prognostic difference between IMPC and IDC. We analysed 327 cases of IMPC patients and 4979 IDC cases who underwent primary resection in our institution between 2008 and 2012. Using propensity score matching, the two groups were matched at 1:1 by age, tumour size, nodal status, hormone status, and HER2 status. Differences in prognosis were assessed by Kaplan-Meier estimates and Cox regression analysis. We established the IMPC group and identified 324 IDC patients by propensity score matching. The survival analysis indicated that IMPC patients had no significant reduced overall survival (p = 0.752) or disease-free survival (p = 0.578) compared with IDC patients. Multivariate Cox regression analysis revealed that IMPC was not an independent prognostic factor for disease-free survival (hazard ratio [HR] = 0.944; 95% confidential interval [CI], 0.601-1.481) or overall survival (HR = 0.727; 95% CI, 0.358-1.478). Survival analysis demonstrated no statistically significant difference between IMPC and IDC, indicating that proactive or radical clinical therapy is unnecessary.}, } @article {pmid30667284, year = {2019}, author = {Lv, T and Wang, Y and Wang, X}, title = {Subgroups of parotid gland infiltrating ductal carcinoma benefit from postoperative radiotherapy: a population-based study.}, journal = {Future oncology (London, England)}, volume = {15}, number = {8}, pages = {885-895}, doi = {10.2217/fon-2018-0495}, pmid = {30667284}, issn = {1744-8301}, mesh = {Age Factors ; Carcinoma, Ductal/mortality/pathology/*therapy ; Chemotherapy, Adjuvant/methods/statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Parotid Gland/pathology/radiation effects/surgery ; Parotid Neoplasms/mortality/pathology/*therapy ; Prognosis ; Radiotherapy, Adjuvant/methods/statistics & numerical data ; SEER Program/*statistics & numerical data ; Survival Rate ; }, abstract = {AIM: To analyze the prognostic factors and the impact of postoperative radiotherapy (PORT) in parotid gland infiltrating ductal carcinoma (IDC).

MATERIALS & METHODS: 252 patients diagnosed with parotid gland IDC were identified from the SEER database. Kaplan-Meier and Cox regression analysis was performed to evaluate the prognostic factors. Propensity score matching was applied then.

RESULTS: Multivariate analysis showed old age and chemotherapy were independent risk factors in parotid gland IDC. Subgroup analysis demonstrated that overall survival (OS) rate of the PORT group was significantly superior to that of the no radiotherapy group in the T3-4 subgroup (p = 0.049), N1 subgroup (p = 0.019) and Tumor, Node, Metastasis (TNM) III subgroup (p = 0.025).

CONCLUSION: PORT improved survival of parotid gland IDC patients within T3-4, N1 and TNM III subgroups.}, } @article {pmid30662932, year = {2019}, author = {Gotlieb, R and Abitbol, J and How, JA and Ben-Brith, I and Abenhaim, HA and Lau, SK and Basik, M and Rosberger, Z and Geva, N and Gotlieb, WH and Mintz, A}, title = {Gender differences in how physicians access and process information.}, journal = {Gynecologic oncology reports}, volume = {27}, number = {}, pages = {50-53}, pmid = {30662932}, issn = {2352-5789}, abstract = {There is an absence of information on how physicians make surgical decisions, and on the effect of gender on the processing of information. A novel web based decision-matrix software was designed to trace experimentally the process of decision making in medical situations. The scenarios included a crisis and non-crisis simulation for endometrial cancer surgery. Gynecologic oncologists, fellows, and residents (42 male and 42 female) in Canada participated in this experiment. Overall, male physicians used more heuristics, whereas female physicians were more comprehensive in accessing clinical information (p < 0.03), utilized alternative-based acquisition processes in the non-crisis scenario (p = 0.01), were less likely to consider procedure-related costs (p = 0.04), and overall allocated more time to evaluate the information (p < 0.01). Further experiments leading to a better understanding of the cognitive processes involved in medical decision making could influence education and training and impact on patient outcome.}, } @article {pmid30661617, year = {2019}, author = {Peleg, Y and Shefer, S and Anavy, L and Chudnovsky, A and Israel, A and Golberg, A and Yakhini, Z}, title = {Sparse NIR optimization method (SNIRO) to quantify analyte composition with visible (VIS)/near infrared (NIR) spectroscopy (350 nm-2500 nm).}, journal = {Analytica chimica acta}, volume = {1051}, number = {}, pages = {32-40}, doi = {10.1016/j.aca.2018.11.038}, pmid = {30661617}, issn = {1873-4324}, mesh = {Meat Proteins/analysis ; Octanes/analysis ; Spectroscopy, Near-Infrared/*methods ; Ulva/chemistry ; Vehicle Emissions/analysis ; Zea mays/chemistry ; }, abstract = {Visual-Near-Infra-Red (VIS/NIR) spectroscopy has led the revolution in high-throughput phenotyping methods used to determine chemical and structural elements of organic materials. In the current state of the art, spectrophotometers used for imaging techniques are either very expensive or too large to be used as a field-operable device. In this study we developed a Sparse NIR Optimization method (SNIRO) that selects a pre-determined number of wavelengths that enable quantification of analytes in a given sample using linear regression. We compared the computed complexity time and the accuracy of SNIRO to Marten's test, to forward selection test and to LASSO all applied to the determination of protein content in corn flour and meat and octane number in diesel using publicly available datasets. In addition, for the first time, we determined the glucose content in the green seaweed Ulva sp., an important feedstock for marine biorefinery. The SNIRO approach can be used as a first step in designing a spectrophotometer that can scan a small number of specific spectral regions, thus decreasing, potentially, production costs and scanner size and enabling the development of field-operable devices for content analysis of complex organic materials.}, } @article {pmid30659137, year = {2019}, author = {Traylor, M and Tozer, DJ and Croall, ID and Lisiecka-Ford, DM and Olorunda, AO and Boncoraglio, G and Dichgans, M and Lemmens, R and Rosand, J and Rost, NS and Rothwell, PM and Sudlow, CLM and Thijs, V and Rutten-Jacobs, L and Markus, HS and , }, title = {Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n = 11,226).}, journal = {Neurology}, volume = {92}, number = {8}, pages = {e749-e757}, pmid = {30659137}, issn = {1526-632X}, support = {FS/15/61/31626/BHF_/British Heart Foundation/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; RG/16/4/32218/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adult ; Aged ; Brain Ischemia/diagnostic imaging/*genetics ; Cerebral Small Vessel Diseases/diagnostic imaging/*genetics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rho Guanine Nucleotide Exchange Factors/*genetics ; Stroke/diagnostic imaging/*genetics ; Stroke, Lacunar/diagnostic imaging/genetics ; White Matter/*diagnostic imaging ; }, abstract = {OBJECTIVE: To identify novel genetic associations with white matter hyperintensities (WMH).

METHODS: We performed a genome-wide association meta-analysis of WMH volumes in 11,226 individuals, including 8,429 population-based individuals from UK Biobank and 2,797 stroke patients. Replication of novel loci was performed in an independent dataset of 1,202 individuals. In all studies, WMH were quantified using validated automated or semi-automated methods. Imputation was to either the Haplotype Reference Consortium or 1,000 Genomes Phase 3 panels.

RESULTS: We identified a locus at genome-wide significance in an intron of PLEKHG1 (rs275350, β [SE] = 0.071 [0.013]; p = 1.6 × 10[-8]), a Rho guanine nucleotide exchange factor that is involved in reorientation of cells in the vascular endothelium. This association was validated in an independent sample (overall p value, 2.4 × 10[-9]). The same single nucleotide polymorphism was associated with all ischemic stroke (odds ratio [OR] [95% confidence interval (CI)] 1.07 [1.03-1.12], p = 0.00051), most strongly with the small vessel subtype (OR [95% CI] 1.09 [1.00-1.19], p = 0.044). Previous associations at 17q25 and 2p16 reached genome-wide significance in this analysis (rs3744020; β [SE] = 0.106 [0.016]; p = 1.2 × 10[-11] and rs7596872; β [SE] = 0.143 [0.021]; p = 3.4 × 10[-12]). All identified associations with WMH to date explained 1.16% of the trait variance in UK Biobank, equivalent to 6.4% of the narrow-sense heritability.

CONCLUSIONS: Genetic variation in PLEKHG1 is associated with WMH and ischemic stroke, most strongly with the small vessel subtype, suggesting it acts by promoting small vessel arteriopathy.}, } @article {pmid30659022, year = {2019}, author = {Guo, Q and Li, VZ and Nichol, JN and Huang, F and Yang, W and Preston, SEJ and Talat, Z and Lefrère, H and Yu, H and Zhang, G and Basik, M and Gonçalves, C and Zhan, Y and Plourde, D and Su, J and Torres, J and Marques, M and Habyan, SA and Bijian, K and Amant, F and Witcher, M and Behbod, F and McCaffrey, L and Alaoui-Jamali, M and Giannakopoulos, NV and Brackstone, M and Postovit, LM and Del Rincón, SV and Miller, WH}, title = {MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ.}, journal = {Cancer research}, volume = {79}, number = {7}, pages = {1646-1657}, pmid = {30659022}, issn = {1538-7445}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; R21 CA226567/CA/NCI NIH HHS/United States ; PJT-156269//CIHR/Canada ; MOP-142281//CIHR/Canada ; }, mesh = {Animals ; Breast Carcinoma In Situ/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; CRISPR-Cas Systems ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Heterografts ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Nodal Protein/*metabolism ; Protein Serine-Threonine Kinases/genetics/*metabolism ; *Signal Transduction ; }, abstract = {The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A-derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. SIGNIFICANCE: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.}, } @article {pmid30656087, year = {2018}, author = {Martell, K and Long, K and Solis, A and Olivotto, IA}, title = {Systemic Lupus Erythematosus is Not Necessarily a Contraindication to Adjuvant Breast Radiation Therapy.}, journal = {Cureus}, volume = {10}, number = {11}, pages = {e3584}, pmid = {30656087}, issn = {2168-8184}, abstract = {A 41-year-old woman presented with pT4dN1aM0, right-sided, inflammatory breast cancer. She had a co-morbid diagnosis of systemic lupus erythematosus (SLE) at the age of 20 and was found to have significant kidney involvement (lupus-associated nephritis) at the age of 28. She went on to receive six cycles of neoadjuvant chemotherapy consisting of fluorouracil, epirubicin, cyclophosphamide, and docetaxcel (FEC-D) after which she had radiographically stable disease. She then had definitive treatment with bilateral mastectomy. Pathology showed a 4-cm residual invasive ductal carcinoma in the right breast and three residual metastatic lymph nodes in the right axilla. After extensive discussions with the patient, which included counseling on the potential increased risk of radiation-induced side effects, she received 50.4 Gy in 28 fractions of adjuvant radiotherapy (RT) to the chest wall and regional lymphatics including the internal mammary chains (IMCs). To minimize the risk of pulmonary toxicity, RT field arrangement consisted of a field-in-field modulated supraclavicular anterior/posterior parallel pair matched to shallow, photon tangent pair with 0.5 cm bolus to the lateral aspect of the chest wall and two matched direct anterior electron fields of 9 MeV with 1 cm bolus and 12 MeV with 0.5 cm bolus medially to cover the remaining residual chest wall and IMCs. This was immediately followed by a boost of 7.5 Gy in three fractions delivered via a photon tangent pair with 1 cm bolus to an area 6 cm superior and inferior to the surgical scar. Total treatment time was 50 days. The patient tolerated the therapy well but she developed grade three acute dermatitis. There were no pulmonary, shoulder joint movement, or brachial plexus side effects. This case is unusual in that SLE is generally considered a contraindication for elective RT. However, given her high risk for breast cancer recurrence, RT was offered with additional caution to minimize lung dose. Having completed the treatment, the side effects experienced were no greater than what would be expected in someone who did not have a diagnosis of SLE.}, } @article {pmid30652428, year = {2019}, author = {Liu, Y and Ide, Y and Inuzuka, M and Tazawa, S and Kanada, Y and Matsunaga, Y and Kuwayama, T and Sawada, T and Akashi-Tanaka, S and Nakamura, S}, title = {BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ.}, journal = {Molecular genetics & genomic medicine}, volume = {7}, number = {3}, pages = {e493}, pmid = {30652428}, issn = {2324-9269}, mesh = {Adult ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology/*genetics ; Female ; Genetic Testing/standards ; Humans ; Incidence ; Japan ; *Mutation ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations.

METHODS: A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).

RESULTS: (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266-20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023-0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092-23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER-positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR.

CONCLUSION: DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.}, } @article {pmid30647841, year = {2018}, author = {Kothari, C and Ouellette, G and Labrie, Y and Jacob, S and Diorio, C and Durocher, F}, title = {Identification of a gene signature for different stages of breast cancer development that could be used for early diagnosis and specific therapy.}, journal = {Oncotarget}, volume = {9}, number = {100}, pages = {37407-37420}, pmid = {30647841}, issn = {1949-2553}, abstract = {Breast cancer (BC) is a heterogeneous disease where the survival rate of patients decreases with progression of the disease. BC usually has a linear progression, classified into normal/benign, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). This study aimed to identify gene signature for each of these subgroups. We performed human transcriptome array analysis on 5 patient samples from each Normal, ADH, IDC and DCIS and 2 replicates of MCF10A cell line representative of each subgroup. We identified SFRP1 and snoRNAs (especially SNORD115 and SNORD114) as the initial regulators of cancer progression, accompanied by significant changes in extracellular matrix organization. Tumor progression to the IDC stage showed upregulation of tumor promoting genes responsible for increased invasion, inflammation, survival in stress environment and metastasis. The gene signatures identified in this study could represent potential biomarkers for each subgroup of breast cancer progression, which could assist in early diagnosis of breast cancer progression as well as treatment interventions. Moreover, these gene signatures could serve in discovery of specific targeted therapies for each subgroup.}, } @article {pmid30633152, year = {2019}, author = {Peng, JH and Zhang, X and Song, JL and Ran, L and Luo, R and Li, HY and Wang, YH}, title = {Neoadjuvant chemotherapy reduces the expression rates of ER, PR, HER2, Ki67, and P53 of invasive ductal carcinoma.}, journal = {Medicine}, volume = {98}, number = {2}, pages = {e13554}, pmid = {30633152}, issn = {1536-5964}, mesh = {Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/*metabolism/pathology ; Drug Therapy, Combination ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {To analyze whether neoadjuvant chemotherapy (NAC) changes the expression rates of invasive ductal carcinoma (IDC) markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, and P53.This was a retrospective study of 112 IDC patients who underwent NAC (docetaxel+epirubicin/pirarubicin+cyclophosphamide) but without pathological complete response (pCR) in 2012 to 2013 at the First Affiliated Hospital of Chongqing Medical University. The IDC subtypes and tumor protein markers were analyzed by immunohistochemistry (IHC). Specific changes in tumor protein markers before/after NAC were compared.The decrease in the positive rate of Ki-67 was the most significant, from 75.9% before NAC to 41.1% after NAC (P < .001). The positive rate of HER2 decreased from 42.0% before NAC to 32.1% after NAC (P = .04). The positive rate of ER decreased from 66.1% before NAC to 56.2% after NAC (P = .04). Increased number of metastatic lymph nodes (P = .006) and body mass index (BMI) (P = .028) seemed to be related to conversion of PR (positive to negative). There was statistical association between the Ki-67 (positive to negative) with the age greater or equal to 50 (P = .015). The BMI greater or equal to 24 (P = .021), age greater or equal to 50 (P = .047), and blood type A (P = .038) were independently associated with conversion of P53 (positive to negative). The BMI greater or equal to 24 (P = .004), number of metastatic lymph nodes greater or equal to 1 (P = .029) and TNM stages I-II (P = .008) were statistically associated with change of HER2 (positive to negative).In patients without pCR, NAC leads to changes in Ki-67, HER2, and hormone receptor (HR) expression. Age, BMI, number of metastatic lymph nodes, and TNM stage are associated with some changes of markers.}, } @article {pmid30629053, year = {2019}, author = {Griffanti, G and Jiang, W and Nazhat, SN}, title = {Bioinspired mineralization of a functionalized injectable dense collagen hydrogel through silk sericin incorporation.}, journal = {Biomaterials science}, volume = {7}, number = {3}, pages = {1064-1077}, doi = {10.1039/c8bm01060a}, pmid = {30629053}, issn = {2047-4849}, mesh = {Animals ; Bone Marrow Cells/cytology ; Cell Differentiation/drug effects ; Cells, Cultured ; Collagen/*chemistry ; Core Binding Factor Alpha 1 Subunit/metabolism ; Durapatite/metabolism ; Gene Expression/drug effects ; Hydrogels/*chemistry/pharmacology ; Mesenchymal Stem Cells/cytology/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Scanning ; Osteocalcin/metabolism ; Osteogenesis/drug effects ; Sericins/*chemistry ; Spectroscopy, Fourier Transform Infrared ; Thermogravimetry ; }, abstract = {Collagen based hydrogels are frequently used as templates to mimic the native biomineralization process. However, a lack of structural control and their inherently poor mineralization capability represent challenges when used as bone-extracellular-matrix mimicking constructs. The aspiration-ejection of highly-hydrated collagen gels allows for their densification and fibrillar remodelling, leading to the production of injectable dense collagen (I-DC) gel scaffolds characterized by an osteoid-like structure. In this study, silk-extracted sericin (SS), a negatively-charged protein that is rich in anionic amino-acids such as Asp and Glu, was hybridized into I-DC gels to induce hydroxyapatite deposition and stimulate the osteoblastic differentiation of seeded mesenchymal stem cells (MSCs). The effect of SS content on the acellular mineralization of I-DC gels in simulated body fluid (SBF) and on modulating the proliferation and osteogenesis of seeded MSCs, in vitro, were investigated. Methylene blue staining indicated increasingly negatively charged gels through SS incorporation. Attributable to the carboxyl groups provided by the acidic SS amino-acids, serving as calcium-phosphate nucleation sites, there was a time dependent increase in hydroxyapatite deposition, approaching 90 wt% by day 14 in SBF. Three dimensionally seeded MSCs attached and proliferated in all gel types and SS-incorporation led to an increase in their metabolic activity. Relative to neat I-DC gels, alkaline phosphatase (at day 7), runt related transcription factor 2 (at day 21) and osteocalcin (at days 14 and 21) expression was higher in MSCs when seeded in SS-incorporated I-DC gels. Cell-induced mineralization was accelerated in SS-incorporated I-DC gels suggesting its osteostimulative potential. In sum, SS incorporation into clinically relevant I-DC gels can provide a strategy to design scaffolds with potential applications in bone tissue engineering.}, } @article {pmid30626860, year = {2019}, author = {Murabayashi, T and Koshita, S and Masu, K and Kanno, Y and Ogawa, T and Okada, T and Oikawa, M and Noda, Y and Sawai, T and Ito, K}, title = {[Detection of small pancreatic cancer during surveillance of the main pancreatic duct stenosis].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {116}, number = {1}, pages = {99-108}, doi = {10.11405/nisshoshi.116.99}, pmid = {30626860}, issn = {0446-6586}, mesh = {Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic ; Endosonography ; Humans ; Male ; Pancreatectomy ; Pancreatic Ducts ; *Pancreatic Neoplasms ; }, abstract = {An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.}, } @article {pmid30621656, year = {2019}, author = {Framarino-Dei-Malatesta, M and Chiarito, A and Bianciardi, F and Fiorelli, M and Ligato, A and Naso, G and Pecorella, I}, title = {Metastases to extraocular muscles from breast cancer: case report and up-to-date review of the literature.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {36}, pmid = {30621656}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging/drug therapy/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Muscle Neoplasms/*diagnosis/diagnostic imaging/pathology/secondary ; Neoplasm Metastasis ; Piperazines/therapeutic use ; Pyridines/therapeutic use ; }, abstract = {BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer.

CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months.

CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.}, } @article {pmid30621628, year = {2019}, author = {Zhu, L and Chen, K}, title = {Clinicopathological features, treatment patterns, and prognosis of squamous cell carcinoma of the breast: an NCDB analysis.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {26}, pmid = {30621628}, issn = {1471-2407}, support = {2017B030314026//Guangdong Science and Technology Department/ ; }, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/drug therapy/*pathology/radiotherapy/surgery ; Carcinoma, Squamous Cell/drug therapy/*pathology/radiotherapy/surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; *Prognosis ; Progression-Free Survival ; }, abstract = {BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare malignancy. The clinicopathological features, treatment patterns and prognosis of SCC of the breast is still unclear.

METHODS: In this study, we performed a 1:4 SCC-IDC (infiltrating ductal carcinoma) matching analysis of patients diagnosed between 2004 and 2014, using the data from the national cancer database. We used Chi-square test to compare the clinicopathological features and treatment patterns between SCC (n = 686) and IDC (n = 2744) patients. We used Kaplan-Meier analysis and Cox-regression to estimate the survival of SCC and IDC patients.

RESULTS: We observed that SCC patients are more likely to have T3-4, grade III, and ER negative diseases, when compared to IDC patients. Breast conserving surgery (BCS) (58.3% vs 65.4%, p = 0.048), as well as radiotherapy after BCS (65.3% vs. 83.0%, p < 0.001), was less performed in SCC patients. Among low-risk patients, chemotherapy was used more often for SCC patients (42.9%) than for IDC (18.7%) patients (p = 0.002). In HR-positive patients, endocrine therapy was used less often for SCC patients (51.6%) than for IDC patients (70.5%) (p < 0.001). SCC (vs. IDC) was associated with no responses to neoadjuvant chemotherapy (20% vs. 5.05%, p = 0.019). Adjusted analysis confirmed that SCC (vs. IDC) was associated with worse OS (HR = 1.40, 95%CI 1.17-1.67, P < 0.01), after a median follow-up of 58.3 months. In SCC patients, HR status is not prognostic of OS, but endocrine therapy was significantly associated with improved OS in HR-positive SCC patients.

CONCLUSIONS: We conclude that SCC is associated with poorer clinicopathological features, no responses to neoadjuvant chemotherapy and worse clinical outcomes than IDC. The treatment patterns for SCC and IDC are different. Endocrine therapy is necessary for HR-positive SCC patients.}, } @article {pmid30619463, year = {2018}, author = {Wang, J and He, ZY and Dong, Y and Sun, JY and Zhang, WW and Wu, SG}, title = {The Distribution and Outcomes of the 21-Gene Recurrence Score in T1-T2N0 Estrogen Receptor-Positive Breast Cancer With Different Histologic Subtypes.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {638}, pmid = {30619463}, issn = {1664-8021}, abstract = {Background: The clinical value of 21-gene recurrence score (RS) in various breast cancer histologic subtypes is not well established. Aims: To assess the distribution and outcomes of the 21-gene RS among various T1-T2N0 estrogen receptor-positive breast cancer histologic subtypes. Methods: Using the Surveillance, Epidemiology and End Results database, we investigated the distribution and outcomes of the 21-gene RS among various breast cancer histologic subtypes between 2004 and 2015. The histologic subtypes with 200 or more cases were further analyzed. Results: We identified 83,665 patients including eight histologic subtypes. The most common subtype was invasive ductal carcinoma not otherwise specified (IDC NOS) (77.9%), followed by lobular carcinoma NOS, mixed infiltrating duct and lobular carcinoma (IDC-L), mucinous adenocarcinoma, tubular adenocarcinoma, micropapillary ductal carcinoma, cribriform carcinoma NOS, and intraductal papillary adenocarcinoma with invasion with 10.8, 7.7, 2.1, 0.6, 0.3, 0.2, and 0.2%, respectively. The 5-years breast cancer specific survival (BCSS) was 98.8, 98.8, 98.9, 99.6, 100, 100, 100, and 100%, respectively (P = 0.011). Patients with IDC NOS (8.9%), micropapillary ductal carcinoma (8.8%), and intraductal papillary adenocarcinoma with invasion (8.2%) had significantly higher percentage of high-risk RS compared to other histologic subtypes (1.0-3.8%) (P < 0.001). The mean RS was higher in IDC NOS, lobular carcinoma NOS, and IDC-L compared to other subtypes. In multivariate analysis, 21-gene RS was the independent prognostic factor in patients with IDC NOS (P < 0.001), lobular carcinoma NOS (P < 0.001), and IDC-L (P < 0.001), patients with a higher RS was associated with poor BCSS. Conclusion: Our results demonstrate that there is a significant difference in distribution of 21-gene RS in T1-T2N0 estrogen receptor-positive breast cancer with different histologic subtypes. Long-term studies with larger series are needed to confirm the role of the 21-gene RS array in prognosis assessment and chemotherapy decision-making in special histologic subtypes with favorable prognosis.}, } @article {pmid30617943, year = {2019}, author = {Modafferi, S and Ries, M and Calabrese, V and Schmitt, CP and Nawroth, P and Kopf, S and Peters, V}, title = {Clinical Trials on Diabetic Nephropathy: A Cross-Sectional Analysis.}, journal = {Diabetes therapy : research, treatment and education of diabetes and related disorders}, volume = {10}, number = {1}, pages = {229-243}, pmid = {30617943}, issn = {1869-6953}, support = {SFB 11118//Deutsche Forschungsgemeinschaft/ ; }, abstract = {INTRODUCTION: Treatment options and decisions are often based on the results of clinical trials. We have evaluated the public availability of results from completed, registered phase III clinical trials on diabetic nephropathy and current treatment options.

METHODS: This was a cross-sectional analysis in which STrengthening the Reporting of OBservational studies in Epidemiology criteria were applied for design and analysis. In June 2017, 34 completed phase III clinical trials on diabetic nephropathy in the ClinicalTrials. gov registry were identified and matched to publications in the ClinicalTrials.gov registry and to those in the PubMed and Google Scholar databases. If no publication was identified, the principal investigator was contacted. The ratio of published and non-published studies was calculated. Various parameters, including study design, drugs, and comparators provided, were analyzed.

RESULTS: Drugs/supplements belonged to 26 different categories of medications, with the main ones being angiotensin-converting enzyme inhibitors, angiotensin-II receptors blockers, and dipeptidyl-peptidase-4-inhibitors. Among the trials completed before 2016 (n = 32), 22 (69%) were published, and ten (31%) remained unpublished. Thus, data on 11 different interventions and more than 1000 patients remained undisclosed. Mean time to publication was 26.5 months, which is longer than the time constrictions imposed by the U.S. Food and Drug Administration Amendments Act. Most trials only showed weak effects on micro- and macroalbuminuria, with an absolute risk reduction of 1.0 and 0.3%, respectively, and the number needed to treat varied between 91 and 333, without any relevant effect on end-stage-renal disease by intensive glucose-lowering treatment. Comparison of the results, however, was difficult since study design, interventions, and the renal outcome parameters vary greatly between the studies.

CONCLUSION: Despite the financial and human resources involved and the relevance for therapeutic guidelines and clinical decisions, about one-third of phase III clinical trials on diabetic nephropathy remain unpublished. Interventions used in published trials showed a low efficacy on renal outcome.

FUNDING: Deutsche Forschungsgemeinschaft (DFG): SFB 1118.}, } @article {pmid30614407, year = {2020}, author = {Shenkman, G and Shmotkin, D}, title = {Self-Perceived Parental Role and Mental Health Concomitants Among Israeli Gay and Heterosexual Fathers.}, journal = {Journal of homosexuality}, volume = {67}, number = {5}, pages = {712-732}, doi = {10.1080/00918369.2018.1555392}, pmid = {30614407}, issn = {1540-3602}, mesh = {Adult ; Depression/psychology ; Fathers/*psychology ; Heterosexuality/*psychology ; Homosexuality, Male/*psychology ; Humans ; Male ; *Mental Health ; Parenting/*psychology ; Parents/psychology ; *Self Concept ; Sexual and Gender Minorities ; }, abstract = {In this study we examined the association between self-perceived parental role and adverse mental health (indicated by depressive symptoms, neuroticism, and negative affect) in a sample of 82 Israeli gay fathers (Mean age = 39.57, SD = 6.70) that were individually matched with 82 heterosexual fathers (Mean age = 39.11, SD = 7.88). Results showed that although self-perceived parental role was associated with adverse mental health, this association was moderated by sexual orientation, such that a significant negative association between self-perceived parental role and adverse mental health was evident only among gay fathers. The findings are understood by features of gay fatherhood, which is intentional and purposeful, and usually achieved after contending with particular difficulties in the journey to fatherhood. These features presumably shape the perceived parental role, and thus may link more strongly with lower levels of adverse mental health among gay fathers, compared to heterosexual fathers.}, } @article {pmid30608397, year = {2019}, author = {Bertozzi, S and Cedolini, C and Londero, AP and Baita, B and Giacomuzzi, F and Capobianco, D and Tortelli, M and Uzzau, A and Mariuzzi, L and Risaliti, A}, title = {Sentinel lymph node biopsy in patients affected by breast ductal carcinoma in situ with and without microinvasion: Retrospective observational study.}, journal = {Medicine}, volume = {98}, number = {1}, pages = {e13831}, pmid = {30608397}, issn = {1536-5964}, mesh = {Aged ; Breast/pathology ; Breast Carcinoma In Situ/mortality/pathology/*surgery ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Micrometastasis ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy/*mortality ; }, abstract = {With the introduction of an organized mammographic screening, the incidence of ductal carcinoma in situ (DCIS) has experienced an important increase. Our experience with sentinel lymph node biopsy (SLNB) among patients with DCIS is reviewed.We collected retrospective data on patients operated on their breasts for DCIS (pTis), DCIS with microinvasion (DCISM) (pT1mi) and invasive ductal carcinoma (IDC) sized ≤2 cm (pT1) between January 2002 and June 2016, focusing on the result of SLNB.543 DCIS, 84 DCISM, and 2111 IDC were included. In cases of DCIS and DCISM, SLNB resulted micrometastatic respectively in 1.7% and 6.0% of cases and macrometastatic respectively in 0.9% and 3.6% of cases. 5-year disease-free survival and overall survival in DCISM and IDC were similar, while significantly longer in DCIS. 5-year local recurrence rate of DCIS and DCISM were respectively 2.5% and 7.9%, and their 5-year distant recurrence rate respectively 0% and 4%. IDC, tumor grading ≥2 and lymph node (LN) macrometastasis were significant predictors for decreased overall survival. Significant predictors for distant metastases were DCISM, IDC, macroscopic nodal metastasis, and tumor grading ≥2. Predictors for the microinvasive component in DCIS were tumor multifocality/multicentricity, grading ≥2, ITCs and micrometastases.Our study suggests that despite its rarity, sentinel node metastasis may also occur in case of DCIS, which in most cases are micrometastases. Even in the absence of an evident invasive component, microinvasion should always be suspected in these cases, and their management should be the same as for IDC.}, } @article {pmid30607556, year = {2019}, author = {Wang, G and Zhou, C and Conklin, C and Hayes, MM and Villamil, CF and Ostry, A and Jones, EC}, title = {Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {474}, number = {3}, pages = {333-339}, pmid = {30607556}, issn = {1432-2307}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Carcinoma, Squamous Cell/chemistry/mortality/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Time Factors ; Urinary Bladder Neoplasms/chemistry/mortality/*secondary/therapy ; }, abstract = {Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.}, } @article {pmid30607162, year = {2018}, author = {Byun, KD and Hwang, HJ and Park, KJ and Kim, MC and Cho, SH and Ju, MH and Lee, JH and Jeong, JS}, title = {T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer.}, journal = {Journal of breast cancer}, volume = {21}, number = {4}, pages = {406-414}, pmid = {30607162}, issn = {1738-6756}, abstract = {PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role.

METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed.

RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006).

CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.}, } @article {pmid32146794, year = {2019}, author = {Karanis, M and Koksal, H and Ates, E and Dogru, O}, title = {Clinical importance of fibulin-5 immunohistochemical staining in breast lesions.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {70}, number = {4}, pages = {259-263}, doi = {10.5114/pjp.2019.93127}, pmid = {32146794}, issn = {1233-9687}, mesh = {Breast ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Lobular/diagnosis ; Extracellular Matrix Proteins/*analysis ; Female ; Fibroadenoma/*diagnosis ; Humans ; Immunohistochemistry ; Staining and Labeling ; Triple Negative Breast Neoplasms ; }, abstract = {The aim of this study was to evaluate the clinical importance of fibulin-5, which has been shown to display tumour-promoting and tumour-protective functions in breast lesions. Sixty-two breast cancer patients, 19 patients with fibroadenoma, and 15 healthy breast tissues were enrolled. Forty-seven patients had invasive ductal carcinoma (IDC) (12 of them also had in situ carcinoma DCIS), and 15 had invasive lobular carcinoma (ILC). A scoring system from 0 to 4 was used to evaluate the fibulin-5 staining according to the percentage of stained cells. The median values of fibulin-5 staining scores of the breast cancer, fibroadenoma, and healthy breast tissues were 2 (range: 0-4), 3 (range: 3-4), and 4 (range: 1-4), respectively, and the difference is statistically significant (p = 0.0001). There was no significant difference between the fibulin-5 scores of IDC, ILC, and DCIS. Fifteen patients with triple-negative breast cancer (TNBC) had the lowest fibulin-5 score (p < 0.0001). The median fibulin-5 scores of the patients according to Ki-67 index ≥ 14% and < 14% were 2 (range: 1-5) and 4 (range: 1-5), respectively, and the difference is statistically significant (p = 0.001). These data can be explained by the inhibitory effect of fibulin-5 on epithelial cell proliferation, which is closely related to differentiation and prognosis.}, } @article {pmid30594914, year = {2019}, author = {Khorshidi, H and Azari, I and Oskooei, VK and Taheri, M and Ghafouri-Fard, S}, title = {DSCAM-AS1 up-regulation in invasive ductal carcinoma of breast and assessment of its potential as a diagnostic biomarker.}, journal = {Breast disease}, volume = {38}, number = {1}, pages = {25-30}, doi = {10.3233/BD-180351}, pmid = {30594914}, issn = {1558-1551}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Ductal, Breast/*diagnosis/*genetics ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Association Studies ; Humans ; Middle Aged ; RNA, Long Noncoding/*genetics ; Real-Time Polymerase Chain Reaction ; Tamoxifen/therapeutic use ; Up-Regulation ; }, abstract = {BACKGROUND: The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance.

OBJECTIVE: To evaluate expression profile of DSCAM-AS1 in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer.

METHODS: We evaluated expression of DSCAM-AS1 in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR.

RESULTS: DSCAM-AS1 was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P = 0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P = 0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer.

CONCLUSIONS: The significant up-regulation of DSCAM-AS1 in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer.}, } @article {pmid30589573, year = {2018}, author = {Pascual-Vera, B and Roncero, M and Doron, G and Belloch, A}, title = {Assisting relapse prevention in OCD using a novel mobile app-based intervention: A case report.}, journal = {Bulletin of the Menninger Clinic}, volume = {82}, number = {4}, pages = {390-406}, doi = {10.1521/bumc.2018.82.4.390}, pmid = {30589573}, issn = {1943-2828}, mesh = {Adult ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; *Mobile Applications ; Obsessive-Compulsive Disorder/prevention & control/*therapy ; Secondary Prevention/instrumentation/*methods ; }, abstract = {Mobile health apps increase the accessibility of cognitive-behavioral-based interventions before, during, or following treatment. GGOC is a mobile app designed to challenge maladaptive beliefs in obsessive-compulsive disorder (OCD). This single-case study assesses the usefulness of GGOC as a relapse prevention tool for OCD. The patient was a 26-year-old woman with severe contamination and washing/cleaning OCD symptoms (Y-BOCS = 33). GGOC was used for relapse prevention following CBT treatment. The patient completed 47 levels dedicated to OCD-relevant maladaptive beliefs. Before and after GGOC, the Y-BOCS, Obsessive-Compulsive Inventory (OCI-R), Obsessive Beliefs Questionnaire (OBQ-20), and Depression subscale of the Depression, Anxiety, Stress Scale were completed. The OBQ-20 and OCI-R scores decreased from pre- to post-GGOC. The Y-BOCS decreased from 7 pre-GGOC to 2 post-GGOC. Findings support the efficacy of GGOC as a relapse prevention tool for individuals with OCD, and its contribution to maintaining gains after CBT.}, } @article {pmid30589304, year = {2019}, author = {Gibson, BS and Healey, MK and Gondoli, DM}, title = {ADHD reflects impaired externally directed and enhanced internally directed attention in the immediate free-recall task.}, journal = {Journal of abnormal psychology}, volume = {128}, number = {2}, pages = {173-183}, doi = {10.1037/abn0000393}, pmid = {30589304}, issn = {1939-1846}, mesh = {Adolescent ; Analysis of Variance ; Attention/*physiology ; Attention Deficit Disorder with Hyperactivity/diagnosis/*psychology ; Child ; Cognition/physiology ; Female ; Humans ; Male ; Memory, Episodic ; Memory, Short-Term/*physiology ; Motivation/physiology ; }, abstract = {Previous attempts to understand the neurocognitive mechanisms underlying attention-deficit/hyperactivity disorder (ADHD) may be limited by the tendency to focus exclusively on "externally directed cognition" (EDC) while ignoring "internally directed cognition" (IDC; Dixon, Fox, & Christoff, 2014. There is clear evidence that ADHD reflects deficiencies in EDC because of weaknesses in modulatory, motivational, and cognitive control constructs, but little is currently known about the integrity of IDC in ADHD. In the present study, we used a verbal episodic memory task involving immediate free recall to assess the integrity of EDC and IDC in a sample of 111 adolescents, 50 with study-confirmed diagnoses of ADHD and 61 without. The ADHD group was found to have significantly worse scores on outcomes that depend on EDC during encoding (serial position), and significantly better scores on outcomes that depend on IDC during retrieval (lag-conditional response probabilities). In addition, model parameters estimating the contribution of EDC and IDC processes were fit to these data using the retrieved context model of memory search. The model suggested that, during encoding, the ADHD group had slower mental context drift, indicative of weaker externally directed attention to the list items, as well as deficiencies in their ability to allocate and sustain attention when the study list first appeared. During retrieval, in contrast, the model suggested that the ADHD group had faster mental context drift indicative of stronger internally directed attention to retrieved context. These findings provide novel evidence that ADHD reflects impaired EDC and enhanced IDC, and they reinforce the clinical relevance of distinguishing EDC and IDC in future studies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, } @article {pmid30587740, year = {2018}, author = {Yano, Y and Kuga, T and Harada, T and Sano, F and Inokuchi, T and Fujii, Y}, title = {[A Case of Suspected Therapy-Related Leukemia after Chemotherapy for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {12}, pages = {1775-1777}, pmid = {30587740}, issn = {0385-0684}, mesh = {*Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; *Leukemia/chemically induced ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasms, Second Primary ; Sentinel Lymph Node Biopsy ; }, abstract = {Therapy-related leukemia(TRL)is a distinctive clinical syndrome that occurs after exposure to chemotherapy or radiotherapy. We report a case of suspected TRLafter chemotherapy in a patient with breast cancer. A 61-year-old woman underwent total mastectomy and sentinel lymph node biopsy(negative)for her breast cancer. Histopathologic analysis showed invasive ductal carcinoma, pStage I. Her subtype histology was Luminal B-type, and postoperative adjuvant chemotherapy and endocrine therapy were administered. Four years after chemotherapy, a blood examination showed pancytopenia. Bone marrow examination showed acute promyelocytic leukemia. She was treated with chemotherapy and achieved complete remission. Breast cancer provides long-term survival after treatment. Attention should be paid to the occurrence of TRLin breast cancer surveillance.}, } @article {pmid30587150, year = {2018}, author = {Zhao, J and Hu, C and Wang, C and Yu, W and Guo, Y and Shi, M and Shui, Y and Wei, Q}, title = {Breast cancer primary tumor ER expression pattern predicts its expression concordance in matched synchronous lymph node metastases.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1290}, pmid = {30587150}, issn = {1471-2407}, support = {K17-518052-002//Zhejiang University Research Foundation/ ; }, mesh = {Axilla ; Biopsy ; Breast/pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Mastectomy ; Middle Aged ; Receptors, Estrogen/analysis/*metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Estrogen receptor (ER) expression is important for treatment selection and prognostication of breast cancer patients. Although the metastases are the main targets of endocrine therapy, ER status is often based on the primary tumor. However, ER expression in breast cancer primary lesion may not match with its synchronous metastatic lesions in some cases. In this study, we analyzed ER expression concordance between breast cancer primary tumor and metastatic lesions.

METHODS: Paraffin blocks of 100 primary breast invasive ductal carcinoma cases with axillary lymph node metastases were collected. Five tissue cores were punched out from individual primary breast cancer, and one tissue core from each lymph node metastases to assemble tissue microarrays for ER staining. Samples were then scored as 0, 1+, 2+, and 3+ according to the number and intensity of ER stained tumor cells.

RESULTS: For cases with ER 3+ (strong expression) in all cores of primary lesions (n = 38), ER expression in metastatic lymph node was found in 94.7% of the patients. 91.0% of the metastatic lymph nodes were ER positive, and 84.3% of them to be 3+. Among the 46 cases of ER negative expression in all cores of primary lesions, 39 of them had all the metastatic nodes being ER negative, and ER negative nodes were seen in 95.7% of the metastases. As for 16 cases of ER inconsistent expression in primary lesions, 4 cases showed negative ER expression in all metastatic nodes, 2 cases displayed diffuse consistent ER 3+ expression, and 10 cases displayed variant ER expression.

CONCLUSIONS: The findings suggest that ER expression concordance between breast cancer primary lesion and its matched metastatic lesions could be estimated by primary tumor ER expression pattern.}, } @article {pmid30585372, year = {2019}, author = {Currin, S and Flood, TA and Krishna, S and Ansari, A and McInnes, MDF and Schieda, N}, title = {Intraductal carcinoma of the prostate (IDC-P) lowers apparent diffusion coefficient (ADC) values among intermediate risk prostate cancers.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {50}, number = {1}, pages = {279-287}, doi = {10.1002/jmri.26594}, pmid = {30585372}, issn = {1522-2586}, mesh = {Aged ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging ; Case-Control Studies ; Diffusion ; Humans ; Male ; Middle Aged ; Multiparametric Magnetic Resonance Imaging ; Neoplasm Grading ; Prostate/*diagnostic imaging ; Prostate-Specific Antigen/blood ; *Prostatectomy ; Prostatic Neoplasms/*diagnostic imaging ; Retrospective Studies ; Risk ; Seminal Vesicles/pathology ; }, abstract = {BACKGROUND: Prostatic intraductal carcinoma (IDC-P) is an aggressive variant of prostate cancer (PCa) characterized by proliferation of malignant cells within prostatic ducts/acini and nucleomegaly.

PURPOSE/HYPOTHESIS: To compare apparent diffusion coefficient (ADC) values and Prostate Imaging and Data Reporting System (PI-RADS) v. 2 scores in intermediate risk (International Society of Urological Pathology [ISUP] Grade Group [GG] 2 and 3) PCa with/without IDC-P to determine if IDC-P alters the MRI appearance of PCa.

STUDY TYPE: Retrospective, case-control.

POPULATION: Fifteen consecutive men with ISUP GG 2/3 (Gleason score 3+4 = 7 [N = 4], 4+3 = 7 [N = 11]) PCa with IDC-P diagnosed at radical prostatectomy were compared with: 1) ISUP GG 2/3 PCa without IDC-P (matched for percentage Gleason pattern 4), and 2) ISUP GG 4 and 5 (Gleason score 8/9) PCa without IDC-P.

FIELD STRENGTH/SEQUENCE: 3T multiparametric MRI.

ASSESSMENT: Two blinded radiologists (R1/R2) measured mean ADC, ADC.ratio (ADC.tumor/ADC.normal peripheral zone) and assigned PI-RADS v2 scores. Statistical Tests: Chi-square and analysis of variance (ANOVA).

RESULTS: There were no differences in age, prostate serum antigen, tumor size, or stage between groups (P = 0.063-0.912). Tumors with IDC-P had lower mean ADC and ADC.ratio (0.741 ± 0.152 mm[2] /sec and 0.44 ± 0.07) compared with ISUP GG 2/3 tumors without IDC-P (0.888 ± 0.167 mm[2] /sec and 0.62 ± 0.14), P = 0.012 and <0.001; and did not differ compared with ISUP GG 4/5 tumors (0.705 ± 0.141 mm[2] /sec and 0.44 ± 0.08), P = 0.509 and 0.868. Tumors with IDC-P were nearly all PI-RADS v2 score 5 (14/15) compared with ISUP GG 2/3 tumors without IDC-P (10/15 R1, 8/15 R2) and GG 4/5 tumors (9/15), (P = 0.040 = 0.092). Agreement in PI-RADS v2 scoring was moderate (K = 0.68).

DATA CONCLUSION: ISUP GG 2 and 3 (intermediate risk, Gleason score 7) PCa with IDC-P have lower ADC compared with tumors without IDC-P with a similar percentage of Gleason pattern 4 and resemble ISUP GG 4 and 5 high risk tumors on MRI. IDC-P lowers ADC values among intermediate risk prostate cancers.

LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:279-287.}, } @article {pmid30584319, year = {2018}, author = {Liu, M and Zhang, L and Guo, L and Lv, J and Shi, W and Liu, B}, title = {Intestinal metastasis from breast invasive ductal carcinoma after a long latency: case report and literature review.}, journal = {OncoTargets and therapy}, volume = {11}, number = {}, pages = {8599-8603}, pmid = {30584319}, issn = {1178-6930}, abstract = {Intestinal metastasis from breast cancer (BC) is rarely encountered in clinical practice. Nonspecific symptoms and long latency result in misdiagnosis as a primary intestinal tumor. Therefore, increased awareness of bowel metastasis secondary to BC and a thorough understanding of the clinical and molecular features, and intervention of bowel metastasis are fundamental to avoid the delay of correct diagnosis and management. Herein, we documented a BC patient who experienced progressive bellyache and vomiting 16 years after simplified radical mastectomy. Abdominal CT scan revealed localized thickening of the small intestine wall and lumen narrowing, initially diagnosed as a primary intestinal tumor. The subsequent operation resolved the intestinal obstruction and confirmed the diagnosis of intestinal involvement of BC. Radical local treatment followed by systemic intervention contributed to a better outcome. Our case indicates that intestinal metastasis should be included in the diagnostic checklist in patients presented with any intestinal symptom even with a remote history of BC. Our case is of great value in its rarity and calls for the awareness of clinicians for this special entity to guarantee the accurate and prompt diagnosis and treatment, and optimize the patient's prognosis.}, } @article {pmid30583683, year = {2018}, author = {Ayadi, EZ and Cherif, B and Ben Hamed, Y and Mokni, M and Rebai, A and Ayadi, H and Jlidi, R}, title = {Prognostic Value of BCL2 in Women Patients with Invasive Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {12}, pages = {3557-3564}, pmid = {30583683}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymphoma, B-Cell/metabolism/pathology ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism ; Young Adult ; }, abstract = {Background: Breast cancers are heterogeneous, making it essential to recognize several biomarkers for cancer outcome predictions especially in young women where the classical prediction parameters are not suitable. The goal from this study is to evaluate the impact of B cell lymphoma 2 (BCL2), P53 and Ki-67 proteins expression on survival in young women patients with invasive ductal carcinoma. Patients and methods: Samples and clinical data from 238 patients were collected between 2003 and 2017. They were selected according to 2 criteria: age ≤40 years old and most of them are affected by an Invasive Ductal Carcinoma. We evaluated BCL2, P53 and ki-67 expression by immunochemistry test, and then we assessed correlations of these biomarkers expression with patient’s clinicopathological characteristics and survival. Results: Triple negative breast cancer group showed a high frequency among our cohort but we emphasize an almost equitable distribution among all molecular groups. Contrary to other studies which reported that luminal A was correlated with better prognosis, our analysis demonstrated that luminal A is correlated with the Scarff, Bloom and Richardson (SBR) grading 2 or SBR grading 3. To better investigate the prognosis, we analyze three biomarkers known by their impact on physiopathology behavior on breast cancer BCL2, ki-67and P53. BCL2 is the more relevant one, it was correlated with molecular subtypes (p=0.0012) and SBR grading (p=0.0016). BCL2 seems to be the good prognostic biomarker related to survival (p=0.004) with a protective role among patients when endocrine therapy is not provided and Lymph Node (LN) involvement is positive (p=0.021, p=0.000 respectively). Conclusions: The classical prognostic parameters based mainly on the molecular classification in breast cancer seem insufficient in the case of young women. BCL2 protein expression analysis provides a better prognostic value. BCL2 should be clinically associated in current practice when young women specimens are diagnosticated.}, } @article {pmid30583129, year = {2018}, author = {Kim, IS and Kim, YI and Hong, JT and Lee, DS}, title = {Rationales for a Urodynamic Study in Patients with Cervical Spondylotic Myelopathy.}, journal = {World neurosurgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.wneu.2018.12.049}, pmid = {30583129}, issn = {1878-8769}, abstract = {BACKGROUND: Detrusor sphincter dyssynergia, involuntary detrusor contractions (IDCs), and poor bladder compliance are common urodynamic findings in cervical spondylotic myelopathy (CSM). There is little information regarding the role of a urodynamic study after decompression surgery for CSM.

METHODS: Urodynamic study was performed before and 6 months after decompression of CSM. Japanese Orthopaedic Association score for cervical myelopathy and Neck Disability Index functional score were applied. International Prostate Symptom Score was applied in male patients, and 6-item Urogenital Distress Inventory was applied in female patients.

RESULTS: Mean patient age was 61.3 years. Final follow-up was obtained in 17 of 32 patients. Neurogenic bladder was confirmed in 11 (64.7%) patients, with 7 patients having poor bladder compliance, 3 patients having IDCs, and 6 patients having detrusor sphincter dyssynergia. Poor bladder compliance was normalized in 4 of 7 patients. IDCs disappeared in 2 (phasic IDCs) of 3 patients and improved in 1 (terminal IDC) patient. Detrusor sphincter dyssynergia markedly improved in 4 of 6 patients. Bladder compliance in 17 patients was 45.52 ± 23.71 before decompression surgery and 77.07 ± 39.85 after decompression surgery (P = 0.004). Both Japanese Orthopaedic Association and Neck Disability Index scores improved (P = 0.007 and P = 0.001, respectively). International Prostate Symptom Score and 6-item Urogenital Distress Inventory were not changed 6 months after surgery.

CONCLUSIONS: Neurogenic bladder could be partially controlled in patients with CSM after surgical decompression. The neurogenic component in the urodynamic study findings varied. Depending on the findings, further appropriate urologic treatments after neurologic decompression surgery should be considered.}, } @article {pmid30582225, year = {2019}, author = {Bertagnolo, V and Grassilli, S and Volinia, S and Al-Qassab, Y and Brugnoli, F and Vezzali, F and Lambertini, E and Palomba, M and Piubello, Q and Orvieto, E and Natali, C and Piva, R and Croce, CM and Capitani, S}, title = {Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {5}, pages = {708-721}, pmid = {30582225}, issn = {1098-2744}, support = {FIRB RBAP10Z7FS_002//Italian MIUR/International ; IG 170631//Associazione Italiana per la Ricerca sul Cancro/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Proliferation ; Female ; Follow-Up Studies ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Stem Cells/metabolism/*pathology ; Phospholipase C beta/genetics/*metabolism ; Prognosis ; Tumor Cells, Cultured ; }, abstract = {Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS-derived cells, we demonstrate that PLC-β2 is up-regulated in DCIS and that its forced down-modulation induces an epithelial-to-mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC-β2 in non-transformed and DCIS-derived cells is, to some extent, dependent on the de-regulation of miR-146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR-146a in targeting PLC-β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC-β2/miR-146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC-β2/miR-146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence.}, } @article {pmid30580361, year = {2018}, author = {Tengku Din, TADAA and Abdul Jalal, MI and Seeni, A and Shamsuddin, S and Jaafar, H}, title = {The differential roles of caspase family members in mediating PF4-induced breast cancer apoptosis.}, journal = {The Malaysian journal of pathology}, volume = {40}, number = {3}, pages = {303-312}, pmid = {30580361}, issn = {0126-8635}, mesh = {Animals ; Apoptosis/*drug effects/physiology ; Caspases/*metabolism ; Female ; Mammary Glands, Animal/drug effects/*metabolism/pathology ; Mammary Neoplasms, Experimental/*metabolism/pathology ; Platelet Factor 4/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; }, abstract = {INTRODUCTION: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer.

MATERIALS AND METHODS: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 μg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining.

RESULTS: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups.

CONCLUSION: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.}, } @article {pmid30578311, year = {2019}, author = {Pérez-Garcia, J and Cortés, J and Metzger Filho, O}, title = {Efficacy of Single-Agent Chemotherapy for Patients with Advanced Invasive Lobular Carcinoma: A Pooled Analysis from Three Clinical Trials.}, journal = {The oncologist}, volume = {24}, number = {8}, pages = {1041-1047}, pmid = {30578311}, issn = {1549-490X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*drug therapy/mortality/pathology ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology ; Carcinoma, Lobular/*drug therapy/mortality/pathology ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Female ; Furans/*administration & dosage/adverse effects ; Humans ; Ketones/*administration & dosage/adverse effects ; Middle Aged ; Progression-Free Survival ; Receptor, ErbB-2/analysis/metabolism ; Receptors, Estrogen/analysis/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. We investigated the efficacy of single-agent eribulin for the treatment of advanced ILC when compared with invasive ductal carcinoma (IDC).

PATIENTS AND METHODS: Results from the eribulin arms of two phase III studies (305 [EMBRACE] and 301) and a single-arm, phase II study were pooled. The studies involved patients with metastatic breast cancer who had previously received treatment with an anthracycline and a taxane. In all three studies, the dose of eribulin mesylate was 1.4 mg/m[2] given on days 1 and 8 of a 21-day cycle. Overall survival (OS), progression-free survival (PFS), and response rates in patients with ILC were assessed and compared with data from patients with IDC.

RESULTS: In total, 1,152 patients were included in this analysis (118 patients with ILC and 1,034 patients with IDC). Median OS was similar in patients with ILC and IDC (13.4 vs. 13.5 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.87-1.38); as was median PFS (4.1 vs. 3.6 months; HR, 0.91; 95% CI, 0.72-1.14). There were no major differences in response rates between the two groups.

CONCLUSION: This retrospective analysis suggests that eribulin demonstrates similar efficacy in patients with ILC and IDC with metastatic disease who have previously received an anthracycline and a taxane.

IMPLICATIONS FOR PRACTICE: Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. This pooled retrospective analysis of three clinical studies demonstrates that the magnitude of benefit of eribulin in the metastatic setting did not differ between patients with ILC versus invasive ductal carcinoma (IDC), even when restricting for patients with estrogen receptor-positive/HER2-negative IDC.}, } @article {pmid30577820, year = {2018}, author = {Liu, F and Wang, M and Li, H}, title = {Role of perfusion parameters on DCE-MRI and ADC values on DWMRI for invasive ductal carcinoma at 3.0 Tesla.}, journal = {World journal of surgical oncology}, volume = {16}, number = {1}, pages = {239}, pmid = {30577820}, issn = {1477-7819}, support = {YKK14181//General Subject of Nanjing Medical Science and Technology Development/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; *Contrast Media ; Diffusion Magnetic Resonance Imaging/*instrumentation/*methods ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Perfusion ; Prognosis ; Prospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The value of apparent diffusion coefficient (ADC) values and quantitative parameters (Ktrans, Kep, Ve) in detecting prognostic factor at 3.0 Tesla remains unclear, especially in predicting prognosis of breast cancer.

METHODS: A total of 151 patients with IDC underwent breast DCE-MRI and DWI-MRI at 3.0 Tesla following surgery. The ADC values were acquired with b values of 0 and 1000 s/mm[2]. The relationship between ADC values or DCE-MRI quantitative parameters and size, histologic grade (HG), lymph node metastasis (LNM), ER, PR, and Ki67 was evaluated. The predictive values of ADC, Ktrans, Kep, and Ve to prognosis of IDC were assessed.

RESULTS: ADC value was positively related to size (P = 0.04) and HER2 (P = 0.046) expression and negatively related to ER (P = 0.012) and PR (P < 0.001) expression. Ktrans value has positive correlation with size (P < 0.001), HG (P < 0.001), LNM (P < 0.001), HER2 (P = 0.007), and Ki67 (P < 0.001) expression and negative correlation with ER (P < 0.001) and PR (P < 0.001) expression. Kep value was positively related to size (P < 0.001) and negatively related to ER (P < 0.001) and PR (P < 0.001) expression. Ve value was negatively related to HER2 expression (P = 0.004). The Cox hazard ratio (HR) of ADC, Ktrans, Kep, and Ve values on survival was 5.26 (P = 0.093), 1.081 (P = 0.002), 1.006 (P = 0.941), and 0.883 (P = 0.926), respectively.

CONCLUSIONS: Ktrans value was a best predictive indicator of HG, LNM, ER, PR, and Ki67 expression, and ADC value was the best predictive indicator of HER2. Preoperative use of the 3.0 Tesla could provide important information to determine the optimal treatment plan.}, } @article {pmid30577784, year = {2018}, author = {Ssemmanda, S and Katagirya, E and Bukirwa, P and Alele, D and Lukande, R and Kalungi, S}, title = {Breast diseases histologically diagnosed at a tertiary facility in Uganda (2005-2014).}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1285}, pmid = {30577784}, issn = {1471-2407}, mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Female ; Fibroadenoma/diagnosis/*epidemiology/pathology ; Humans ; Male ; Risk Factors ; Uganda/epidemiology ; }, abstract = {BACKGROUND: The prevalence and distribution of histologically diagnosed breast disease are not well documented in low income countries, Uganda inclusive. Although the greater majority of breast lesions globally are benign, breast cancer is the most frequently diagnosed cancer all over the world. We aimed at documenting the prevalence of different breast diseases histologically diagnosed at the histopathology laboratory of the Department of Pathology of the Makerere University College of Health Sciences (MakCHS Lab) over a decade (2005-2014). We also describe the demographic characteristics of the patients in Uganda diagnosed with breast disease at the MakCHS Lab during the same period.

METHODS: This was a 10 year retrospective study of histologically diagnosed breast disease between 2005 and 2014 inclusive at the MakCHS Lab. We extracted information from hard copies of all 2510 histopathology reports retrieved from archives of the Department of Pathology at the MakCHS Lab. 640 records that were either damaged beyond recognition of key details, were duplicated, were implausible or had no conclusive diagnosis made were excluded. Information to be analyzed was then entered into Epidata (version 3.1) on a password protected laptop. Data analysis was done using SPSS software (v16 for Windows × 64).

RESULTS: From the 1870 patients' records eventually analyzed, breast disease was most diagnosed in female patients (97.1%). The overall mean age for breast disease diagnosis was 33 years (S.D ± 16.46) and median age 26 years (IQR: 20-43). Fibroadenoma (40.1%) was the most diagnosed breast disease overall. We noticed steadily increasing frequency of diagnosis of cancerous breast diseases over the last half of the study period. Invasive ductal carcinoma was the most diagnosed breast cancer (326 cases, 55.6%). A high female to male breast cancer ratio of 48:1 was observed. The highest regional breast cancer proportion was from the Western region of the Country.

CONCLUSIONS: There is need for more research into the picture of breast disease in the country, covering various demographic characteristics of the country's population for all regions and informing about its incidence rates and prevalence and also the breast cancer risk estimate for benign breast disease.}, } @article {pmid30570854, year = {2018}, author = {Sunar, V and T Dogan, H and Sarici, F and Ates, O and Akin, S and Baspinar, B and Aksoy, S and Altundag, K}, title = {Association between androgen receptor status and prognosis in triple negative breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {23}, number = {5}, pages = {1325-1330}, pmid = {30570854}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Carcinoma, Lobular/metabolism/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/*metabolism ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/metabolism/*pathology/therapy ; }, abstract = {PURPOSE: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients.

METHODS: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with ≥1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC.

RESULTS: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC.

CONCLUSION: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.}, } @article {pmid30567280, year = {2018}, author = {Khalil, N and Fowler, C}, title = {Misconceptions surrounding pregnancy-associated breast cancer.}, journal = {BMJ case reports}, volume = {11}, number = {1}, pages = {}, pmid = {30567280}, issn = {1757-790X}, mesh = {Adult ; Breast Neoplasms/*diagnosis/diagnostic imaging/therapy ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/therapy ; Combined Modality Therapy ; Delivery, Obstetric ; Diagnosis, Differential ; Female ; Humans ; Infant, Newborn ; Mammography ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/diagnostic imaging/therapy ; Pregnancy Trimester, First ; Triple Negative Breast Neoplasms/*diagnosis/diagnostic imaging/therapy ; *Ultrasonography, Prenatal ; }, abstract = {This case report describes a 31-year-old woman who presented with a right painless breast lump. A mammogram and ultrasound scan showed the lump was suspicious of cancer. Core biopsy and immunohistochemistry of the lump confirmed a triple negative, poorly differentiated, invasive ductal carcinoma of the right breast. One week following her diagnosis, the patient found out she was pregnant. The patient was worried about what the implications this diagnosis would have on both her baby and her own cancer treatment.}, } @article {pmid30562656, year = {2019}, author = {Abazari, R and Mahjoub, AR and Shariati, J}, title = {Synthesis of a nanostructured pillar MOF with high adsorption capacity towards antibiotics pollutants from aqueous solution.}, journal = {Journal of hazardous materials}, volume = {366}, number = {}, pages = {439-451}, doi = {10.1016/j.jhazmat.2018.12.030}, pmid = {30562656}, issn = {1873-3336}, mesh = {Adsorption ; Anti-Bacterial Agents/*chemistry ; Metal-Organic Frameworks/*chemistry ; *Nanostructures ; Solutions ; Ultrasonic Waves ; Water Pollutants, Chemical/*chemistry ; }, abstract = {In this study, various sonochemical conditions were applied to prepare the microsheets, nanosheets and nanoflowers of a metal-organic framework (MOF; [Zn6(IDC)4(OH)2(Hprz)2]n) that is composed of Zn(II) cations coordinated with the linear N-donor piperazine (prz) and rigid planar imidazole-4,5-dicarboxylate (H3IDC) ligands. The PXRD patterns approved purity of the samples and the FT-IR spectra related the detected bonds and functional groups to [Zn6(IDC)4(OH)2(Hprz)2]n crystals. The morphological results indicated that any changes in the synthesis conditions can affect nucleation and morphology of the nanostructures. The prepared MOF nanosheets and nanoflowers (with particle size average of 95 and 116 nm, respectively) were employed to adsorb the ampicillin, amoxicillin and cloxacillin antibiotics. Then, the MOFs were calcined at 550 ℃ and atmospheric pressure to produce ZnO nanoparticles and the resultant nanoparticles were adopted to photodegrade the antibiotics. These nanoparticles can photodegrade 37% of the amoxicillin compounds within 180 min. Among the examined samples, the nanoflowers demonstrated the highest adsorption capacity by eliminating 92.5%, 88% and 89% of the antibiotic molecules from the 60-ppm amoxicillin, ampicillin and cloxacillin solutions, respectively. Also, these nanoflowers are thermally stable up to 365 ℃. The associated adsorption process was found to follow pseudo-first-order kinetics, in the case of amoxicillin.}, } @article {pmid30562218, year = {2019}, author = {Alkhasawneh, A and Nassri, A and John, I}, title = {Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.}, journal = {The American Journal of dermatopathology}, volume = {41}, number = {7}, pages = {502-504}, doi = {10.1097/DAD.0000000000001322}, pmid = {30562218}, issn = {1533-0311}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Dedifferentiation ; Female ; GATA3 Transcription Factor/metabolism ; Humans ; Keratins/metabolism ; Lymphatic Metastasis ; Melanoma/metabolism/*secondary ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology ; Skin Neoplasms/metabolism/*pathology/secondary ; }, abstract = {Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.}, } @article {pmid30559551, year = {2018}, author = {Carneiro, GAC and Pereira, FPA and Lopes, FPPL and Calas, MJG}, title = {Magnetic resonance imaging-guided vacuum-assisted breast biopsy: experience and preliminary results of 205 procedures.}, journal = {Radiologia brasileira}, volume = {51}, number = {6}, pages = {351-357}, pmid = {30559551}, issn = {0100-3984}, abstract = {OBJECTIVE: To demonstrate the frequency of malignancy and histological characteristics of lesions in patients submitted to vacuum-assisted breast biopsy guided by magnetic resonance imaging (MRI).

MATERIALS AND METHODS: This was a retrospective study of MRI-guided vacuum-assisted breast biopsies performed between April 2008 and December 2016, in which we analyzed clinical and epidemiological data, as well as the BI-RADS classification and histopathological results. We compared nodules and non-nodular enhancements, in terms of their correlation with malignancy, using chi-square test.

RESULTS: Among 215 cases referred for MRI-guided vacuum-assisted breast biopsy, the procedure was contraindicated in 10 cases (5%) and was technically feasible in the remaining 205 (95%). Non-nodular enhancements were observed in 135 cases (66%), and nodules were observed in 70 (34%), with a mean diameter of 2.2 cm (range, 0.5-9.6 cm) and 0.97 cm (range, 0.5-2.2 cm), respectively. Of the 205 lesions analyzed, 43 (21%) were malignant, 129 (63%) were benign, and 33 (16%) were classified as high-risk lesions. The most common histological findings were invasive ductal carcinoma and, in high-risk cases, lobular neoplasia. There was no significant difference between nodules and non-nodular enhancements in terms of the rate of malignancy (p = 0.725).

CONCLUSION: In our sample, the overall malignancy rate was 21%. However, to improve the assessment of these results, it is necessary to correlate them with the surgical data and with data from the follow-up of benign cases.}, } @article {pmid30558571, year = {2018}, author = {Semango, GP and Charles, RM and Swai, CI and Mremi, A and Amsi, P and Sonda, T and Shao, ER and Mavura, DR and Joosten, LAB and Sauli, E and Nyindo, M}, title = {Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1258}, pmid = {30558571}, issn = {1471-2407}, support = {001//Tanzania Commission for Science and Technology/ ; }, mesh = {Adolescent ; Adult ; Age Factors ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; HIV Infections/*complications/immunology ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Referral and Consultation ; Retrospective Studies ; Risk Factors ; Sarcoma, Kaposi/*epidemiology ; Sex Factors ; Tanzania ; Young Adult ; }, abstract = {BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015.

METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration.

RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/μl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010).

CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.}, } @article {pmid30558095, year = {2018}, author = {Li, Y and Peng, Y and He, X}, title = {A highly aggressive invasive ductal carcinoma from a complex cystic breast mass and BI-RADS assessment: A case report.}, journal = {Medicine}, volume = {97}, number = {50}, pages = {e13740}, pmid = {30558095}, issn = {1536-5964}, mesh = {Biopsy, Fine-Needle/*adverse effects/methods ; Breast/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*pathology/surgery ; Female ; Fibrocystic Breast Disease/pathology ; Humans ; Middle Aged ; Neoadjuvant Therapy/methods ; Treatment Outcome ; Ultrasonography, Mammary/methods ; }, abstract = {RATIONALE: The term cystic breast lesions is a sonographic diagnosis, which can be categorized as simple, complicated or complex. The complex cysts are deemed as having a low risk of breast cancer. The highly aggressive invasive ductal carcinomas among complex cysts, in particular, are infrequent reported.

PATIENT CONCERNS: A 56-year-old female with a breast complex cyst who, after fine-needle aspiration, complained about oozing with fluid as well as skin ulceration that did not heal.

DIAGNOSES: An advanced HER-2-enriched invasive ductal carcinoma was diagnosed.

INTERVENTIONS: The patient received neoadjuvant chemotherapy of anti-HER-2 target drug, palliative surgery and following postoperative chemotherapy.

OUTCOMES: The patient was in good general condition at 6 months follow-up after surgery.

LESSONS: Meticulous ultrasound evaluation of Breast Imaging Reporting and Data System (BI-RADS) category is crucial and indispensable when a complex cyst is found. The radiologist and clinician should be fully awake to its possibility of malignancy, especially fast-growing one in post-menopausal women. Excision biopsy may be preferred for diagnosis.}, } @article {pmid30557036, year = {2019}, author = {Dabarian, AL and Mady, C and Barbosa-Ferreira, JM and Ianni, BM and Hotta, VT and Ramires, FJA and Lopes, HF and Buck, PC and Pessoa, FG and Fonseca, KCB and Nogueira, AR and Fernandes, F}, title = {Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels.}, journal = {Canadian journal of physiology and pharmacology}, volume = {97}, number = {2}, pages = {140-145}, doi = {10.1139/cjpp-2018-0349}, pmid = {30557036}, issn = {1205-7541}, mesh = {Adipokines/*blood/metabolism ; Adult ; Autonomic Nervous System/physiopathology ; Cardiomyopathy, Dilated/blood/diagnosis/*metabolism/physiopathology ; Chagas Cardiomyopathy/blood/diagnosis/*metabolism/physiopathology ; Echocardiography, Doppler ; Electrocardiography ; Female ; Heart ; Heart Rate/physiology ; Humans ; Insulin/*blood/metabolism ; Male ; Middle Aged ; }, abstract = {Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.}, } @article {pmid30555634, year = {2018}, author = {Durand, N and Borges, S and Hall, T and Bastea, L and Döppler, H and Edenfield, BH and Thompson, EA and Geiger, X and Storz, P}, title = {The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.}, journal = {Oncotarget}, volume = {9}, number = {91}, pages = {36358-36370}, pmid = {30555634}, issn = {1949-2553}, support = {R21 CA184527/CA/NCI NIH HHS/United States ; }, abstract = {Phosphatidylinositol-4-phosphate 5-kinase type-1C (PIP5K1C) is a lipid kinase that regulates focal adhesion dynamics and cell attachment through site-specific formation of phosphatidylinositol-4,5-bisphosphate (PI4,5P2). By comparing normal breast tissue to carcinoma in situ and invasive ductal carcinoma subtypes, we here show that the phosphorylation status of PIP5K1C at serine residue 448 (S448) can be predictive for breast cancer progression to an aggressive phenotype, while PIP5K1C expression levels are not indicative for this event. PIP5K1C phosphorylation at S448 is downregulated in invasive ductal carcinoma, and similarly, the expression levels of PKD1, the kinase that phosphorylates PIP5K1C at this site, are decreased. Overall, since PKD1 is a negative regulator of cell migration and invasion in breast cancer, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.}, } @article {pmid30554991, year = {2019}, author = {Gaudet, M and Pharand-Charbonneau, M and Wright, D and Nguyen, J and Trudel-Sabourin, J and Chelfi, M}, title = {Long-term results of multicatheter interstitial high-dose-rate brachytherapy for accelerated partial-breast irradiation.}, journal = {Brachytherapy}, volume = {18}, number = {2}, pages = {211-216}, doi = {10.1016/j.brachy.2018.11.004}, pmid = {30554991}, issn = {1873-1449}, mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/*therapy ; Female ; Humans ; Middle Aged ; *Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Radiotherapy Dosage ; Radiotherapy, Adjuvant ; Survival Rate ; Time Factors ; }, abstract = {PURPOSE: The purpose of this study was to report the long-term results of women treated in one center with accelerated partial-breast irradiation (APBI) with interstitial high-dose-rate (HDR) brachytherapy.

MATERIALS AND METHODS: We analyzed data from women treated in one center with adjuvant interstitial HDR brachytherapy for early-stage breast cancer. Treatment regimen was homogeneous for all women with treatment dose 32Gy in 8 fractions twice daily given to the tumor bed with interstitial HDR brachytherapy.

RESULTS: About 364 women were treated with interstitial HDR brachytherapy as APBI from March 2000 to March 2014. Mean age at diagnosis was 62 years. Stage distribution was as follows: T1a = 12%, T1b = 33%, T1c = 40%, T2 = 14%, and Tis = 1%. 97% of patients were N0. 88% had invasive ductal carcinoma. 86% had positive hormone receptor status. 14 ipsilateral breast tumor recurrences were identified with 12 deemed local recurrences and 2 deemed to be second ipsilateral primaries. Actuarial 5-year and 10-year overall survival rates were 95.1% and 92.2%, respectively. Actuarial 5-year and 10-year local relapse-free survival rates were 96.2% and 88.8%, respectively.

CONCLUSIONS: The results of this previously unreported series of women treated with a homogeneous APBI method exclusively with interstitial HDR brachytherapy present further data justifying that in appropriately selected women, APBI with interstitial brachytherapy provides rates of local control and survival comparable with whole-breast irradiation.}, } @article {pmid30551691, year = {2018}, author = {Falakian, Z and Shahani, T and Rezaie, R and Mazloomzadeh, S and Sirati, F and Jalilvand, A and Jahangiri, F and Bahmani, P and Jadali, F and Atarian, S and Eghdam-Zamir, R and Biglari, A}, title = {Patients With Invasive Ductal Carcinoma Have Reduced Levels of Decorin Expression in Their Breast Tissue Compared to Patients With Fibroadenoma While Plasma Decorin Remains Unchanged.}, journal = {Archives of Iranian medicine}, volume = {21}, number = {11}, pages = {509-517}, pmid = {30551691}, issn = {1735-3947}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast Neoplasms/blood/*metabolism ; Carcinoma, Ductal, Breast/blood/*metabolism ; Decorin/blood/*metabolism ; Female ; Fibroadenoma/blood/*metabolism ; Fibrocystic Breast Disease/blood/*metabolism ; Humans ; Logistic Models ; Middle Aged ; Neoplasm Staging ; Young Adult ; }, abstract = {BACKGROUND: Reduction in the level of tissue decorin is a hallmark of many types of cancer including breast carcinoma. However, reduced decorin expression has also been reported in several types of benign tumors to the extent that it has been proposed as a tissue marker to differentiate malignant from benign tumors. The aim of this study was to investigate the potential role of plasma decorin to distinguish breast cancer from fibroadenoma, the second most common type of benign tumor, after fibrocystic disease.

METHODS: From 35 patients recruited in this study, 24 were affected with invasive ductal carcinoma, either grade II (n = 14) or grade III (n = 10). The other 11 patients had fibroadenoma lesions in their breasts. Tissue decorin mRNA and protein levels were assessed with real-time qPCR and Immunohistochemical analysis. ELISA was employed to measure plasma levels of decorin.

RESULTS: The mean plasma decorin in cancer patients was measured to be 5.42 ± 1.83 ng/mL while fibroadenoma patients had an average of 4.22 ± 1.17 ng/mL decorin in their plasma. The difference was not significant. However, the mean expression level of decorin mRNA calculated by the 2-ΔΔCt method was 5.6-fold lower in the biopsied tissue specimens of IDC patients versus fibroadenoma, as expected. Consistent reduction in protein abundance was observed in the studied tissue sections.

CONCLUSION: We have shown that tissue decorin is a reliable marker, unaffected by patient disease stage, to differentiate IDC from fibroadenoma. However, plasma decorin does not seem to have diagnostic value in this regard.}, } @article {pmid30549348, year = {2019}, author = {Bonsang, B and Charles, F and Conan-Charlet, V and Guilbert, S and Marcorelles, P and Talagas, M}, title = {Mammary carcinoma with osteoclast-like giant cell: Fine needle aspiration and cytological diagnosis of a rare and misleading subtype of invasive ductal carcinoma.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {30}, number = {3}, pages = {337-339}, doi = {10.1111/cyt.12669}, pmid = {30549348}, issn = {1365-2303}, mesh = {Aged ; Biopsy, Fine-Needle/methods ; Breast Neoplasms/diagnosis/pathology ; Carcinoma, Ductal/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*pathology ; Female ; Giant Cells/*pathology ; Humans ; Osteoclasts/*pathology ; }, } @article {pmid30544169, year = {2019}, author = {Martínez Nicolás, I and Lê Cook, B and Flores, M and Del Olmo Rodriguez, M and Hernández Rodríguez, C and Llamas Sillero, P and Baca-Garcia, E}, title = {The impact of a comprehensive electronic patient portal on the health service use: an interrupted time-series analysis.}, journal = {European journal of public health}, volume = {29}, number = {3}, pages = {413-418}, doi = {10.1093/eurpub/cky257}, pmid = {30544169}, issn = {1464-360X}, mesh = {Ambulatory Care/statistics & numerical data ; Chronic Disease ; Emergency Service, Hospital/statistics & numerical data ; Health Services Research ; Hospitalization/statistics & numerical data ; Humans ; Interrupted Time Series Analysis ; *Patient Portals ; Patient Readmission/statistics & numerical data ; Spain ; *Utilization Review ; }, abstract = {BACKGROUND: There is little empirical research on the potential benefit that electronic patient portals (EPP) can have on the care quality and health outcomes of diverse multi-ethnic international populations. The purpose of this study is to determine the extent to which an EPP was associated with improvements in health service use.

METHODS: Using a quasi-experimental interrupted time-series approach, we assessed health service use before (April 2012-September 2015) and after (October 2015-December 2016) the implementation of a comprehensive EPP at four hospitals in Madrid, Spain. Primary outcomes were number of outpatient visits, any hospital admission, any 30-day all-cause readmission and any emergency department visit.

RESULTS: Implementation of the EPP was associated with a significant decline in readmissions. Among patients with chronic heart failure, EPP implementation was associated with a significant decline for all outcome measures, and among patients with COPD, a decline in all outcomes except readmissions. Among patients diagnosed with malignant hematological diseases, no significant changes were identified.

CONCLUSIONS: EPPs hold promise for reducing hospital readmissions. Certain patient populations with chronic conditions may differentially benefit from portal use depending on their needs for communication with their providers.}, } @article {pmid30542725, year = {2018}, author = {Shettar, A and Damineni, S and Mukherjee, G and Kondaiah, P}, title = {Gap junction β‑2 expression is negatively associated with the estrogen receptor status in breast cancer tissues and is a regulator of breast tumorigenesis.}, journal = {Oncology reports}, volume = {40}, number = {6}, pages = {3645-3653}, doi = {10.3892/or.2018.6764}, pmid = {30542725}, issn = {1791-2431}, mesh = {Animals ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinogenesis/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexin 26 ; Connexins/genetics/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, Nude ; Receptors, Estrogen/*metabolism ; Up-Regulation ; }, abstract = {Gap junction β‑2 gene (GJB2, also known as connexin 26) is a member of the connexin family which forms gap junction channels. Many connexin genes have been considered to be tumor suppressor genes. However, the overexpression of GJB2 has been found to be associated with a poor prognosis in several human cancers. In our previous microarray study, we revealed the overexpression of GJB2 in breast cancer tissues. Hence, in this study, we investigated the expression of GJB2 in human breast cancer and its role in breast cancer cell proliferation and migration. The RT‑qPCR results revealed the upregulation of the GJB2 gene in invasive ductal carcinoma (P<0.001) of the breast. Immunohistochemical analysis revealed an intense cytoplasmic and membrane staining. We observed that the staining for GJB2 was more intense in the majority of the estrogen receptor (ER)‑negative breast cancer tissues compared to the normal breast tissues (P<0.0001). By contrast, the majority of the ER‑positive breast cancer samples exhibited weak to moderate staining; however, this difference was not statistically significant compared to the normal tisues. The knockdown of GJB2 in human breast cancer cell lines using shRNA led to a significant decrease in the proliferative ability and an increase in the migratory ability of breast cancer cells. In addition, the knockdown of GJB‑2 led to a significant reduction in tumor volume and proliferation (as demonstrated by MIB‑1 staining) in orthotopic xenografts in immunocompromised mice. On the whole, the findings of this study indicate that GJB2 may be an important regulator of breast tumorigenesis.}, } @article {pmid30542423, year = {2018}, author = {Zhu, YC and Zhang, Y and Deng, SH and Jiang, Q and Wang, DS}, title = {Correlation between histopathological grading and shear-wave elastography in evaluating invasive carcinoma of no special type.}, journal = {Experimental and therapeutic medicine}, volume = {16}, number = {6}, pages = {4700-4706}, pmid = {30542423}, issn = {1792-0981}, abstract = {The present study aimed to investigate the correlation between histologic grade and shear-wave elastography in evaluating invasive breast carcinoma of no special type (NST). A total of 84 breast lesions in 80 patients (age range, 32-64 years) were retrospectively evaluated. The patients underwent B-mode ultrasound and virtual touch tissue quantification diagnosis. A semi-quantitative method was then applied in order to determine the histologic grade of the invasive carcinoma of NST according to the grading system published by the World Health Organization. Among the 84 breast lesions, 14 (16.7%) were classified as Grade I, while 29 (34.5%) and 41 (48.8%) were determined to be of Grade II and Grade III, respectively. The size of the breast lesions increased with the increase in histological grade (P<0.001). In addition, 29.3% of the Grade-III breast lesions exhibited acoustic enhancement, while the majority of the Grade-I breast lesions (78.6%) exhibited acoustic shadowing (P=0.002). Furthermore, a higher histopathological grade was closely correlated with a higher mean, minimum and maximum shear-wave velocity value (P<0.05). In conclusion, regarding the evaluation of invasive breast carcinoma of NST, the histologic grade was strongly correlated with tissue stiffness; a higher histologic grade was associated with a harder lesion. Therefore, shear-wave elastography may provide important clinical reference values.}, } @article {pmid30524902, year = {2018}, author = {Collignon, A and Silvy, F and Robert, S and Trad, M and Germain, S and Nigri, J and André, F and Rigot, V and Tomasini, R and Bonnotte, B and Lombardo, D and Mas, E and Beraud, E}, title = {Dendritic cell-based vaccination: powerful resources of immature dendritic cells against pancreatic adenocarcinoma.}, journal = {Oncoimmunology}, volume = {7}, number = {12}, pages = {e1504727}, pmid = {30524902}, issn = {2162-4011}, abstract = {Pancreatic adenocarcinoma (PAC) has a poor prognosis. One treatment approach, investigated here, is to reinforce antitumor immunity. Dendritic cells (DCs) are essential for the development and regulation of adaptive host immune responses against tumors. A major role for DCs may be as innate tumoricidal effector cells. We explored the efficacy of vaccination with immature (i)DCs, after selecting optimal conditions for generating immunostimulatory iDCs. We used two models, C57BL/6Jrj mice with ectopic tumors induced by the PAC cell line, Panc02, and genetically engineered (KIC) mice developing PAC. Therapeutic iDC-vaccination resulted in a significant reduction in tumor growth in C57BL/6Jrj mice and prolonged survival in KIC mice. Prophylactic iDC-vaccination prevented subcutaneous tumor development. These protective effects were long-lasting in Panc02-induced tumor development, but not in melanoma. iDC-vaccination impacted the immune status of the hosts by greatly increasing the percentage of CD8[+] T-cells, and natural killer (NK)1.1[+] cells, that express granzyme B associated with Lamp-1 and IFN-γ. Efficacy of iDC-vaccination was CD8[+] T-cell-dependent but NK1.1[+] cell-independent. We demonstrated the ability of DCs to produce peroxynitrites and to kill tumor cells; this killing activity involved peroxynitrites. Altogether, these findings make killer DCs the pivotal actors in the beneficial clinical outcome that accompanies antitumor immune responses. We asked whether efficacy can be improved by combining DC-vaccination with the FOLFIRINOX regimen. Combined treatment significantly increased the lifespan of KIC mice with PAC. Prolonged treatment with FOLFIRINOX clearly augmented this beneficial effect. Combining iDC-vaccination with FOLFIRINOX may therefore represent a promising therapeutic option for patients with PAC.}, } @article {pmid30524164, year = {2018}, author = {Pusina, S}, title = {Correlation of Serum Levels of Urokinase Activation Plasminogen (uPA) and Its Inhibitor (PAI-1) with Hormonal and HER-2 Status in the Early Invasive Breast Cancer.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {72}, number = {5}, pages = {335-340}, pmid = {30524164}, issn = {1986-5961}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood/genetics/pathology ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Plasminogen Activator Inhibitor 1/*blood ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*physiology ; Urokinase-Type Plasminogen Activator/*blood ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the most common malignant tumor in women. On the list of causes of death immediately after lung cancer. It is a heterogeneous disease, considering the differences in morphological, cytogenetic, molecular, clinical and therapeutic aspects, so that the prognosis in a patient with the same histological grade and pathological status may vary.

AIM: In this paper we wanted to identify the correlation between the assay of the serum values of uPA-PAI-1 complexes and individual prognostic-predictive parameters, primarily with the status of estrogenic (Er), progesterogenic (PgR) and Her-2 receptors ("human epidermal growth factor).

MATERIAL AND METHODS: The study was conducted at the Clinic for General and Abdominal Surgery, University Clinical Center of Sarajevo (CCUS), from September 2016 to April 2017. The study included 66 patients, ages 18 to 75, in whom by the needle biopsy preoperatively was pathohistologically verified primary invasive breast cancer.

RESULTS: Two thirds of the sample were classified as invasive ductal carcinoma, similar to the percentage (68.2%) of pT2 size, and almost half in the grade G3. Lymph node status was negative in 54.5% of respondents, and positive in 31.8% of respondents. Most patients had positive estrogenic (83.3%) and progesterone receptors (62.1%). Almost 80% was Her-2 negative. The blood vessel invasion was present in 56.1%, while the neural invasion was present in less than a third of the sample (30.3%). Median values of uPA-PAI-1 complexes were 1.4 (interquartile range 0.9); almost 70% of the sample was negative for the status analysis of uPA-PAI-1 complex (<1).

DISCUSSION: A statistically significant difference was determined in the mean values of uPA-PAI-1 complexes in subgroups according to menopausal status, tumor size, histological grade, histological type (invasive ductal carcinoma vs. invasive lobular cancer versus invasive ductal carcinoma vs. invasive lobular cancer), status axillary lymph nodes, Ki67 status (as binary variables), invasion of the blood vessels and neural invasion, as well as subgroups according to the status of expression of hormonal (estrogen and progesterone) receptors.

CONCLUSION: There is a statistically significant difference in the mean values of the uPA-PAI-1 complex and Her-2 receptor expression. Generally, in perspective, this would be the role played by the uPA/PAI-1 complex in breast cancer, which is that the elevated complex values have a negative prognosis and effect on survival, similar to the negative Her-2 receptor status. Complex uPA/PAI-1 is not a specific serum protein in breast cancer patients and cannot be taken as an individual prognostic-predictive marker for mass pre- or post treatment screening and prediction. Unfortunately, none of the biomarkers are able to independently and fully identify patients of the unknown stage of the disease with better or worse prognosis or to identify cases of more aggressive tumor behavior of the same stage for timely inclusion of adjuvant therapy and reduction of the risk of metastatic disease. The decision on treatment and prognosis should be the result of a combination of all diagnostic, therapeutic, pathohistological and molecular-genetic variables.}, } @article {pmid30538501, year = {2018}, author = {Zhou, H and Lu, K and Zheng, L and Guo, L and Gao, Y and Miao, X and Chen, Z and Wang, X}, title = {Prognostic significance of mammary Paget's disease in Chinese women: a 10-year, population-based, matched cohort study.}, journal = {OncoTargets and therapy}, volume = {11}, number = {}, pages = {8319-8326}, pmid = {30538501}, issn = {1178-6930}, abstract = {PURPOSE: To explore the prognostic significance of mammary Paget's disease (PD) in breast cancer (BC) patients and to investigate the association between clinical manifestation and outcome in invasive ductal carcinoma patients with PD (PD-IDC).

PATIENTS AND METHODS: Eighty-five patients diagnosed with mammary PD with underlying BC from 2006 to 2012 at Zhejiang Cancer Hospital were recruited. A matched group comprised 85 patients diagnosed with BC without PD. Patients were matched according to four variables: stage (0-IV), age at diagnosis (within 5 years), histologic subtype, and the year of surgery. The 74 patients diagnosed with PD-IDC were divided into three groups based on their clinical presentation.

RESULTS: Compared with the matched group, the PD group had more HER2 positivity (P<0.01) and hormone receptor negativity (P<0.01), and a worse outcome (Kaplan-Meier analysis, P<0.001 for disease-free survival and P=0.002 for overall survival). Multivariate Cox regression analyses showed that PD was an independent prognostic predictor for BC patients with PD. In addition, the 22 PD-IDC patients who presented with skin lesions in the nipple/areola and a mass in the breast or axilla had a higher risk of disease relapse than patients who presented with a mass in the breast without skin lesions or patients who presented with skin changes without a palpable mass (adjusted hazards ratio, 0.24; 95% CI, 0.08-0.73; P=0.012 and adjusted hazard ratio, 0.30; 95% CI, 0.06-1.40; P=0.124, respectively).

CONCLUSION: PD is an independent prognostic indicator of outcome in BC patients with PD. Furthermore, the primary symptoms at presentation may be an available indicator of prognosis in PD-IDC.}, } @article {pmid30536119, year = {2019}, author = {Rojas, KE and Fortes, TA and Borgen, PI}, title = {Leveraging the variable natural history of ductal carcinoma in situ (DCIS) to select optimal therapy.}, journal = {Breast cancer research and treatment}, volume = {174}, number = {2}, pages = {307-313}, doi = {10.1007/s10549-018-05080-0}, pmid = {30536119}, issn = {1573-7217}, mesh = {Breast Neoplasms/*diagnosis/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology ; Disease Progression ; Evidence-Based Medicine ; Female ; Humans ; Incidence ; Incidental Findings ; Mammography/statistics & numerical data ; Precision Medicine ; Retrospective Studies ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma. The authors sought to discuss the evidence suggesting that not all DCIS will progress to invasive disease if left untreated.

RESULTS: Four lines of evidence align to suggest that not all of this in-situ disease progresses to invasive cancer: its prevalence on screening mammography, studies of missed diagnoses, incidental findings in autopsy specimens, and large retrospective reviews of those treated with excision alone.

CONCLUSION: A clearer understanding of the variable history of DCIS coupled with advances in genomic profiling of the disease holds the promise of reducing widespread over-treatment of this non-invasive cancer. Additionally, identification of higher risk of recurrence subsets may select patients for whom more aggressive treatment may be appropriate.}, } @article {pmid30532215, year = {2018}, author = {Bang, JI and Yoon, HJ and Kim, BS}, title = {Clinical utility of FDG uptake within reticuloendothelial system on F-18 FDG PET/CT for prediction of tumor recurrence in breast cancer.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0208861}, pmid = {30532215}, issn = {1932-6203}, mesh = {Adult ; Aged ; Bone Marrow/diagnostic imaging/metabolism ; *Breast Neoplasms/diagnosis/metabolism/mortality ; *Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/mortality ; Female ; Glucose-6-Phosphate/administration & dosage/*analogs & derivatives/pharmacokinetics ; Humans ; Liver/diagnostic imaging/metabolism ; Middle Aged ; *Mononuclear Phagocyte System/diagnostic imaging/metabolism ; Neoplasm Metastasis ; *Neoplasm Recurrence, Local/diagnostic imaging/metabolism/mortality ; *Positron-Emission Tomography ; Predictive Value of Tests ; Preoperative Care ; Spleen/diagnostic imaging/metabolism ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: The aim of this study was to investigate the metabolism of the spleen, bone marrow (BM), and liver from preoperative F-18 FDG PET/CT scans for the prediction of recurrence in breast cancer.

METHODS: We retrospectively included 153 patients diagnosed with invasive ductal carcinoma (IDC) of the breast who underwent preoperative F-18 FDG PET/CT scan and a curative operation. The mean standardized uptake value (SUVmean) of the spleen, liver, and BM and maximum SUV (SUVmax) of primary tumors were measured. The relationships between spleen, BM, and liver metabolism and clinicopathologic parameters were evaluated, and possible prognostic parameters predicting recurrence were assessed using disease-free survival (DFS).

RESULTS: Spleen SUVmean was significantly correlated with primary tumor SUVmax, pathologic T (pT) stage, and histologic grade of primary tumor. BM SUVmean also showed a positive correlation with primary tumor SUVmax. Spleen SUVmean were significantly associated with recurrence from binary logistic regression analysis (P = 0.004). Spleen, BM, liver, and primary tumor SUVs were all significant prognostic factors for DFS in univariate Cox regression analysis (all P<0.024). Among all PET parameters analyzed, spleen SUVmean ≥ 2.21 (P = 0.032) was in the multivariable analysis the powerful poor prognostic factor predicting DFS that was independent of other clinicopathological features like T stage (pT >2; P = 0.009) and estrogen receptor (ER) status (ER negativity; P = 0.001).

CONCLUSION: Splenic metabolism together with pT stage and ER status was an independent prognostic factor for predicting recurrence in breast cancer. Metabolic activity of reticuloendothelial system such as spleen, liver or BM on preoperative F-18 FDG PET/CT can be a meritorious imaging factor for discriminating patients with IDC that require adjunctive therapy to prevent recurrence.}, } @article {pmid30531838, year = {2019}, author = {Pearson, SJ and Roy Sarkar, T and McQueen, CM and Elswood, J and Schmitt, EE and Wall, SW and Scribner, KC and Wyatt, G and Barhoumi, R and Behbod, F and Rijnkels, M and Porter, WW}, title = {ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.}, journal = {Oncogene}, volume = {38}, number = {14}, pages = {2611-2626}, pmid = {30531838}, issn = {1476-5594}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; T32 ES026568/ES/NIEHS NIH HHS/United States ; R01 HD083952/HD/NICHD NIH HHS/United States ; R01 ES025209/ES/NIEHS NIH HHS/United States ; R21 CA190941/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*genetics ; BRCA1 Protein/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cadherins/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Repair/genetics ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Genomic Instability/genetics ; Homologous Recombination/*genetics ; Humans ; MCF-7 Cells ; Mice ; Mice, Nude ; Phosphorylation/genetics ; Rad51 Recombinase/genetics ; }, abstract = {There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.}, } @article {pmid30520146, year = {2019}, author = {Mandel, VD and Di Tullio, F and Rugge, W and Coppini, M and Mussini, C and Pellacani, G and Borghi, V}, title = {Optimization strategies for HIV, hepatitis and syphilis testing in Infectious Disease Clinic and Dermatology Unit of Modena: 7-year results of collaboration experience.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {33}, number = {5}, pages = {959-965}, doi = {10.1111/jdv.15390}, pmid = {30520146}, issn = {1468-3083}, mesh = {AIDS Serodiagnosis/*standards ; Adult ; *Ambulatory Care Facilities ; Communicable Diseases ; Cooperative Behavior ; Dermatology ; Female ; Hepatitis B/*diagnosis ; Hepatitis C/*diagnosis ; Humans ; Italy ; Male ; Middle Aged ; Syphilis Serodiagnosis/*standards ; }, abstract = {BACKGROUND: Screening tests for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis infections performed in at-risk population show a higher number of positive tests compared to those carried out in the general population. 'Test & Counselling' Ambulatory of Infectious Disease Clinic (T&C-IDC) and Sexually Transmitted Diseases Ambulatory of Dermatology Unit (STDs-DU) of Modena began collaboration in 2010 and adopted a common diagnostic serological profile since 2013.

OBJECTIVES: The main objective was to analyse the number of screening tests performed in the T&C-IDC and STDs-DU, comparing the results obtained after the adoption of the shared protocol with the previous period. The secondary aim was to evaluate the linkage to care of newly diagnosed patients.

METHODS: Consecutive patients referred to the T&C-IDC and STDs-DU from January 2010 to December 2016, with at least one performed screening test for HIV, HBV, HCV and syphilis were enrolled. Referral of patients with a new infection was obtained by capture-recapture methods in hospital databases.

RESULTS: During the 7-year observation, we collected 13 117 admittances for 9154 patients. A significant increase in the number of screening tests (P < 0.001) and ratio between tests and admissions (P = 0.002) was observed. A total of 644 (7.0%) people with at least one infection were diagnosed. Among these, the most common was syphilis (41.9%), followed by HBV (25.7%), HCV (21.4%) and HIV (10.9%). Syphilis occurred predominantly in Italians (72.5%) and males (75.7%), as like as HCV, while foreign-born (85.5%) mainly harboured HBV infection. HIV diagnosis was detected more frequently among males (67.1%) with a similar proportion between Italians and foreign-born. Five hundred and forty-three out of 644 (84.3%) patients were linked to care.

CONCLUSION: The collaboration between T&C-IDC and STDs-DU has proven to work well increasing the diagnosis over the time and obtaining good results in linkage to care.}, } @article {pmid30519573, year = {2018}, author = {Son, K and Yu, S and Shin, W and Han, K and Kang, K}, title = {A Simple Guideline to Assess the Characteristics of RNA-Seq Data.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2906292}, pmid = {30519573}, issn = {2314-6141}, mesh = {Gene Expression ; High-Throughput Nucleotide Sequencing/*statistics & numerical data ; Humans ; *Principal Component Analysis ; RNA/*genetics ; Sequence Analysis, RNA ; Transcriptome/*genetics ; }, abstract = {Next-generation sequencing (NGS) techniques have been used to generate various molecular maps including genomes, epigenomes, and transcriptomes. Transcriptomes from a given cell population can be profiled via RNA-seq. However, there is no simple way to assess the characteristics of RNA-seq data systematically. In this study, we provide a simple method that can intuitively evaluate RNA-seq data using two different principal component analysis (PCA) plots. The gene expression PCA plot provides insights into the association between samples, while the transcript integrity number (TIN) score plot provides a quality map of given RNA-seq data. With this approach, we found that RNA-seq datasets deposited in public repositories often contain a few low-quality RNA-seq data that can lead to misinterpretations. The effect of sampling errors for differentially expressed gene (DEG) analysis was evaluated with ten RNA-seq data from invasive ductal carcinoma tissues and three RNA-seq data from adjacent normal tissues taken from a Korean breast cancer patient. The evaluation demonstrated that sampling errors, which select samples that do not represent a given population, can lead to different interpretations when conducting the DEG analysis. Therefore, the proposed approach can be used to avoid sampling errors prior to RNA-seq data analysis.}, } @article {pmid30518616, year = {2019}, author = {Metzger-Filho, O and Ferreira, AR and Jeselsohn, R and Barry, WT and Dillon, DA and Brock, JE and Vaz-Luis, I and Hughes, ME and Winer, EP and Lin, NU}, title = {Mixed Invasive Ductal and Lobular Carcinoma of the Breast: Prognosis and the Importance of Histologic Grade.}, journal = {The oncologist}, volume = {24}, number = {7}, pages = {e441-e449}, pmid = {30518616}, issn = {1549-490X}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; }, mesh = {Carcinoma, Ductal, Breast/*diagnosis/mortality/pathology ; Carcinoma, Lobular/*diagnosis/mortality/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The diagnosis of mixed invasive ductal and lobular carcinoma (IDC-L) in clinical practice is often associated with uncertainty related to its prognosis and response to systemic therapies. With the increasing recognition of invasive lobular carcinoma (ILC) as a distinct disease subtype, questions surrounding IDC-L become even more relevant. In this study, we took advantage of a detailed clinical database to compare IDC-L and ILC regarding clinicopathologic and treatment characteristics, prognostic power of histologic grade, and survival outcomes.

MATERIALS AND METHODS: In this retrospective cohort study, we identified 811 patients diagnosed with early-stage breast cancer with IDC-L or ILC. Descriptive statistics were performed to compare baseline clinicopathologic characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan-Meier method and compared using the Cox proportional hazards model.

RESULTS: Patients with ILC had more commonly multifocal disease, low to intermediate histologic grade, and HER2-negative disease. Histologic grade was prognostic for patients with IDC-L but had no significant discriminatory power in patients with ILC. Among postmenopausal women, those with IDC-L had significantly better outcomes when compared with those with ILC: disease-free survival (DFS) and overall survival (OS; adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.31-0.95). Finally, postmenopausal women treated with an aromatase inhibitor had more favorable DFS and OS than those treated with tamoxifen only (OS adjusted HR, 0.50; 95% CI, 0.29-0.87), which was similar for both histologic types (p = .212).

CONCLUSION: IDC-L tumors have a better prognosis than ILC tumors, particularly among postmenopausal women. Histologic grade is an important prognostic factor in IDC-L but not in ILC.

IMPLICATIONS FOR PRACTICE: This study compared mixed invasive ductal and lobular carcinoma (IDC-L) with invasive lobular carcinomas (ILCs) to assess the overall prognosis, the prognostic role of histologic grade, and response to systemic therapy. It was found that patients with IDC-L tumors have a better prognosis than ILC, particularly among postmenopausal women, which may impact follow-up strategies. Moreover, although histologic grade failed to stratify the risk of ILC, it showed an important prognostic power in IDC-L, thus highlighting its clinical utility to guide treatment decisions of IDC-L. Finally, the disease-free survival advantage of adjuvant aromatase inhibitors over tamoxifen in ILC was consistent in IDC-L.}, } @article {pmid30507500, year = {2019}, author = {Wiacek, A and Rindal, OMH and Falomo, E and Myers, K and Fabrega-Foster, K and Harvey, S and Lediju Bell, MA}, title = {Robust Short-Lag Spatial Coherence Imaging of Breast Ultrasound Data: Initial Clinical Results.}, journal = {IEEE transactions on ultrasonics, ferroelectrics, and frequency control}, volume = {66}, number = {3}, pages = {527-540}, pmid = {30507500}, issn = {1525-8955}, support = {R00 EB018994/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast/*diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Signal-To-Noise Ratio ; Ultrasonography, Mammary/*methods ; }, abstract = {Ultrasound is frequently used in conjunction with mammography in order to detect breast cancer as early as possible. However, due largely to the heterogeneity of breast tissue, ultrasound images are plagued with clutter that obstructs important diagnostic features. Short-lag spatial coherence (SLSC) imaging has proven to be effective at clutter reduction in noisy ultrasound images. M -Weighted SLSC and Robust-SLSC (R-SLSC) imaging were recently introduced to further improve image quality at higher lag values, while R-SLSC imaging has the added benefit of enabling the adjustment of tissue texture to produce a tissue signal-to-noise ratio (SNR) that is quantitatively similar to B-mode speckle SNR. This paper investigates the initial application of SLSC, M -Weighted SLSC, and R-SLSC imaging to nine targets in the female breast [two simple cysts, one complicated cyst, two fibroadenomas, one hematoma, one complex cystic and solid mass, one invasive ductal carcinoma (IDC), and one ductal carcinoma in situ (DCIS)]. As expected, R-SLSC beamforming improves cyst and hematoma contrast by up to 6.35 and 1.55 dB, respectively, when compared to the original B-mode image, and similar improvements are achieved with SLSC and M -Weighted SLSC imaging. However, an interesting finding from this initial investigation is that the solid masses (i.e., fibroadenoma, complex cystic and solid mass, IDC, and DCIS), which appear as hypoechoic in the B-mode image, have similarly high coherence to that of surrounding tissue in coherence-based images. This work holds promise for using SLSC, M -Weighted SLSC, and/or R-SLSC imaging to distinguish between fluid-filled and solid hypoechoic breast masses.}, } @article {pmid30502283, year = {2019}, author = {Riba, LA and Russell, T and Alapati, A and Davis, RB and James, TA}, title = {Characterizing Response to Neoadjuvant Chemotherapy in Invasive Lobular Breast Carcinoma.}, journal = {The Journal of surgical research}, volume = {233}, number = {}, pages = {436-443}, doi = {10.1016/j.jss.2018.08.011}, pmid = {30502283}, issn = {1095-8673}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast/pathology/surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*therapy ; Carcinoma, Lobular/mortality/pathology/*therapy ; Cohort Studies ; Databases, Factual/statistics & numerical data ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Receptors, Estrogen/metabolism ; Survival Analysis ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/pathology/*therapy ; United States/epidemiology ; }, abstract = {BACKGROUND: Pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) for breast cancer is associated with improved survival and facilitates conservative surgical strategies. Invasive lobular carcinoma (ILC) has been observed to have decreased response to NCT compared with invasive ductal carcinoma (IDC). This study seeks to evaluate national trends in the use of NCT for ILC compared with IDC, and determine if there is a subset of ILC patients who demonstrate favorable response rates.

METHODS: This is a study using the National Cancer Database. The cohort consisted of patients with stage 1-3 ILC treated between 2010 and 2014, and a reference cohort of patient with IDC. For patients receiving NCT, pCR was assessed and clinically relevant variables were used in multivariable logistic regression models for each histologic subtype, modeling for pCR achievement. Survival analysis was performed for each histologic group to evaluate potential survival benefits of achieving pCR.

RESULTS: Our study cohort consisted of 384,887 women, of which 9.7% had ILC. A significantly lower rate of pCR after NCT was found in the cases of ILC compared with those of IDC (8.7% versus 23.2%). Increased response was seen in ILC patients with HER2-positive and TNBC subtypes. A survival benefit was demonstrated in patients with ILC who achieved pCR.

CONCLUSIONS: While response to NCT in patients with ILC is uncommon, our findings demonstrate a selective benefit for patients with HER2-positive tumors and TNBC. In addition, pCR is correlated with a clear survival advantage in ILC.}, } @article {pmid30502219, year = {2019}, author = {Wang, K and Zhu, GQ and Shi, Y and Li, ZY and Zhang, X and Li, HY}, title = {Long-Term Survival Differences Between T1-2 Invasive Lobular Breast Cancer and Corresponding Ductal Carcinoma After Breast-Conserving Surgery: A Propensity-Scored Matched Longitudinal Cohort Study.}, journal = {Clinical breast cancer}, volume = {19}, number = {1}, pages = {e101-e115}, doi = {10.1016/j.clbc.2018.10.010}, pmid = {30502219}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/surgery ; Carcinoma, Lobular/*mortality/pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Mastectomy, Segmental/*mortality ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*mortality/pathology/surgery ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; SEER Program ; Survival Rate ; }, abstract = {BACKGROUND: The role of histology subtype on the prognosis of T1-2 breast cancer patients receiving breast-conserving surgery (BCS) is not clear.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to compare overall survival, second primary cancer-free survival (CFS), and local recurrence risk (LR) for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), both receiving BCS.

RESULTS: The study enrolled 196,688 patients with T1-2 disease receiving BCS, including 12,906 with ILC and 183,782 with IDC. Patients with IDC showed higher unadjusted annual rates of BCS than ILC. Five- and 10-year estimated survival rates were, respectively, 92.06% and 86.14% in ILC, compared to 90.50% and 85.26% in IDC (P = .12). In multivariable Cox regression, ILC patients showed advantage over IDC in overall survival (hazard ratio [HR] = 0.93, P = .001), whereas no significant differences in CFS (HR = 1.03, P = .33) and LR (HR = 1.17, P = .06) were found, which were consistent with results from matched cohort. In subgroup analyses, patients with grade III ILC had poorer CFS (HR = 1.23, P = .009) and higher LR (HR = 1.59, P = .01) than IDC.

CONCLUSION: Histologic type is of prognostic importance in T1-2 patients receiving BCS, and surgeons should be cautious in performing BCS for individuals with grade III ILC.}, } @article {pmid30512112, year = {2018}, author = {Fitzgerald, EA and Marzalik, PR and Kue, J}, title = {Assessing Intercultural Development Pre- and Post Education Abroad.}, journal = {The Journal of nursing education}, volume = {57}, number = {12}, pages = {747-750}, doi = {10.3928/01484834-20181119-08}, pmid = {30512112}, issn = {1938-2421}, mesh = {*Acculturation ; Cultural Competency/*education ; *Cultural Diversity ; Curriculum ; Education, Nursing, Baccalaureate/*methods ; Humans ; International Educational Exchange ; Nursing Methodology Research ; Students, Nursing/*statistics & numerical data ; }, abstract = {BACKGROUND: There is a need to identify objective measures for growth in the development of intercultural competence for students who engage in education abroad programs of study. The Intercultural Development Inventory® (IDI) identifies the participant's orientation on the Intercultural Development Continuum™ (IDC).

METHOD: Students completed the IDI 4 weeks prior to departure and 8 weeks upon completion of an education abroad program. Students were debriefed by an IDI-qualified administrator.

RESULTS: Group results suggest that students perceived they were further along in the IDC than their actual developmental orientation score revealed.

CONCLUSION: The IDI has promise as a way to measure intercultural development. The IDI enhances preparation of students for participation in an education abroad program. [J Nurs Educ. 2018;57(12):747-750.].}, } @article {pmid30511480, year = {2019}, author = {Srinivasan, SM and Bhat, AN}, title = {Differences in means-end exploration between infants at risk for autism and typically developing infants in the first 15 months of life.}, journal = {Developmental psychobiology}, volume = {61}, number = {2}, pages = {203-215}, pmid = {30511480}, issn = {1098-2302}, support = {R03 HD060809/HD/NICHD NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/*physiopathology ; Child Development/*physiology ; Exploratory Behavior/*physiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant Behavior/*physiology ; Male ; Risk ; }, abstract = {Our study compared means-end exploration in infants at risk (AR) for autism and typically developing (TD) infants using a nested box paradigm. Sixteen AR and 16 TD infants were observed at 9, 12, and 15 months with follow-up at 18 and 24 months. We collected video data on three tasks involving retrieval of a small toy by opening (a) an opaque box, (b) a transparent box, and (c) two nested boxes. Dependent variables included hand bias, time to completion, bilateral hand use, problem-solving strategies used, and tester assistance required. There were no group differences in terms of hand biases. Compared to TD infants, AR infants had lower bilateral hand use, poor problem solving skills, and required greater assistance. Both groups demonstrated age-related improvements in motor and cognitive skills. Means-end exploration provides a window into the bilateral coordination and motor planning/problem-solving abilities of young infants at risk for autism. Lastly, object retrieval tasks could serve as important learning contexts for at-risk infants.}, } @article {pmid30510851, year = {2018}, author = {Soldevilla-Gallardo, I and Medina-Ornelas, SS and Villarreal-Garza, C and Bargalló-Rocha, E and Caro-Sánchez, CH and Hernández-Ramírez, R and Estrada-Lobato, E}, title = {Usefulness of positron emission mammography in the evaluation of response to neoadjuvant chemotherapy in patients with breast cancer.}, journal = {American journal of nuclear medicine and molecular imaging}, volume = {8}, number = {5}, pages = {341-350}, pmid = {30510851}, issn = {2160-8407}, abstract = {Our study examines the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of Neoadjuvant chemotherapy (NAC) with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers. One-hundred and eight patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with [18]F-FDG-PEM scans before and after of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG). After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ± 0.26 vs. 1.9 ± 0.18; P < 0.001) and LTB exhibited a significant decay after the first course of NAC (15.8 ± 1.36 vs. 5.5 ± 0.49; P < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (P = 0.52). Two PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.}, } @article {pmid30499665, year = {2018}, author = {Okada, K and Moon, HJ and Finney, J and Meier, A and Mure, M}, title = {Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity.}, journal = {Biochemistry}, volume = {57}, number = {51}, pages = {6973-6983}, pmid = {30499665}, issn = {1520-4995}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM110761/GM/NIGMS NIH HHS/United States ; R01 GM113101/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Oxidoreductases/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites ; Breast Neoplasms/enzymology ; Cell Line ; Collagen Type IV/metabolism ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Proprotein Convertases/antagonists & inhibitors/genetics/metabolism ; Protein Domains ; Protein Processing, Post-Translational ; Protein-Lysine 6-Oxidase/chemistry/genetics/metabolism ; RNA, Small Interfering/genetics ; Serine Endopeptidases/genetics/metabolism ; }, abstract = {Overexpression of lysyl oxidase-like 2 (LOXL2) is associated with several hepatic and vascular fibrotic diseases and tumor progression in some aggressive cancers. Secreted LOXL2 promotes extracellular matrix cross-linking by catalyzing the oxidative deamination of peptidyl lysine. A great deal remains to be learned about the post-translational modifications of LOXL2, including whether such modifications modulate enzymatic and disease-promoting activities; such knowledge would inform the development of potential therapies. We discovered that upon secretion in cell culture, LOXL2 undergoes proteolytic processing of the first two of four scavenger receptor cysteine-rich domains at the N-terminus. A similar pattern of processing was also evident in tissue extracts from an invasive ductal carcinoma patient. Processing occurred at [314]Arg-[315]Phe-[316]Arg-[317]Lys↓-[318]Ala-, implicating proprotein convertases. siRNA-mediated knockdown of proprotein convertases (furin, PACE4, and PC5/6), as well as incubation with their recombinant forms, showed that PACE4 is the major protease that acts on extracellular LOXL2. Unlike LOX, which requires cleavage of its propeptide for catalytic activation, cleavage of LOXL2 was not essential for tropoelastin oxidation or for cross-linking of collagen type IV in vitro. However, in the latter case, processing enhanced the extent of collagen cross-linking ∼2-fold at ≤10 nM LOXL2. These results demonstrate an important difference in the regulatory mechanisms for LOX and LOXL2 catalytic activity. Moreover, they pave the way for further studies of potential differential functions of LOXL2 isoforms in fibrosis and tumor progression.}, } @article {pmid30498423, year = {2018}, author = {Leithner, D and Kaltenbach, B and Hödl, P and Möbus, V and Brandenbusch, V and Falk, S and Park, C and Vogl, TJ and Müller-Schimpfle, M}, title = {Intraductal Papilloma Without Atypia on Image- Guided Breast Biopsy: Upgrade Rates to Carcinoma at Surgical Excision.}, journal = {Breast care (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {364-368}, pmid = {30498423}, issn = {1661-3791}, abstract = {BACKGROUND: The management of intraductal papilloma without atypia (IDP) in breast needle biopsy remains controversial. This study investigates the upgrade rate of IDP to carcinoma and clinical and radiologic features predictive of an upgrade.

METHODS: Patients with a diagnosis of IDP on image-guided (mammography, ultrasound, magnetic resonance imaging) core needle or vacuum-assisted biopsy and surgical excision of this lesion at a certified breast center between 2007 and 2017 were included in this institutional review board-approved retrospective study. Appropriate statistical tests were performed to assess clinical and radiologic characteristics associated with an upgrade to malignancy at excision.

RESULTS: For 60 women with 62 surgically removed IDPs, the upgrade rate to malignancy was 16.1% (10 upgrades, 4 invasive ductal carcinoma, 6 ductal carcinoma in situ). IDPs with upgrade to carcinoma showed a significantly greater distance to the nipple (63.5 vs. 36.8 mm; p = 0.012). No significant associations were found between upgrade to carcinoma and age, menopausal status, lesion size, microcalcifications, BI-RADS descriptors, initial BI-RADS category, and biopsy modality.

CONCLUSION: The upgrade rate at excision for IDPs diagnosed with needle biopsy was higher than expected according to some guideline recommendations. Observation only might not be appropriate for all patients with IDP, particularly for those with peripheral IDP.}, } @article {pmid30498288, year = {2018}, author = {Netra, SM and Vani, BR and Murthy, VS}, title = {Cytomorphological Study of Medullary Carcinoma of Breast in Comparison to Infiltrating Ductal Carcinoma.}, journal = {Journal of cytology}, volume = {35}, number = {4}, pages = {195-198}, pmid = {30498288}, issn = {0970-9371}, abstract = {INTRODUCTION: Medullary breast carcinoma (MBC) is one of the rare variants of breast carcinoma, accounting for less than 5% of invasive breast carcinoma. MBCs relatively appear a decade earlier when compared to invasive ductal carcinoma (IDC NOS), which is more prevalent in the elderly age.

SUBJECTS AND METHODS: A retrospective study was conducted in the Department of Pathology from 2009 to 2016. Fine needle aspiration cytology slides of MBCs and IDCs were retrieved, studied microscopically, and reviewed to compare the cytological features.

RESULTS: During the study period, MBC cases were 12 and IDC were 319. Random 12 cases of IDC NOS were taken up for comparative cytological evaluation. Various cytological features are assessed and compared using chi square test and independent t test ratio. On comparison of IDC NOS and MBC cases in relation to the parameters like: syncytial clusters and nature of inflammatory infiltrate; the number of positive category was higher in MBC group (83.3%). In contrast, parameters like three-dimensional clusters, acinar pattern, and necrosis; the number of positive category was higher in IDC NOS group with a percentage of 91.7%, 100%, and 67%, respectively. Ratio of lymphoplasmacytic cells to tumor cells between the two showed that the ratio was higher in MBC group. This comparison was statistically significant with a P value of <0.001.

CONCLUSION: Though few variants of breast carcinoma contain lymphoplasmacytic infiltrate, the intensity and pattern of distribution of these lymphocytes and plasma cells in relation to tumor cells helps in distinguishing MBC from other breast carcinomas commonly IDC NOS on cytology. Also MBCs have a better prognosis when compared to IDC NOS.}, } @article {pmid30483242, year = {2018}, author = {Tiong, V and Shu, MH and Wong, WF and AbuBakar, S and Chang, LY}, title = {Nipah Virus Infection of Immature Dendritic Cells Increases Its Transendothelial Migration Across Human Brain Microvascular Endothelial Cells.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2747}, pmid = {30483242}, issn = {1664-302X}, abstract = {Nipah virus (NiV) can infect multiple organs in humans with the central nervous system (CNS) being the most severely affected. Currently, it is not fully understood how NiV spreads throughout the body. NiV has been shown to infect certain leukocyte populations and we hypothesized that these infected cells could cross the blood-brain barrier (BBB), facilitating NiV entry into the CNS. Here, three leukocyte types, primary immature dendritic cells (iDC), primary monocytes (pMO), and monocytic cell line (THP-1), were evaluated for permissiveness to NiV. We found only iDC and THP-1 were permissive to NiV. Transendothelial migration of mock-infected and NiV-infected leukocytes was then evaluated using an in vitro BBB model established with human brain microvascular endothelial cells (HBMEC). There was approximately a threefold increase in migration of NiV-infected iDC across endothelial monolayer when compared to mock-infected iDC. In contrast, migration rates for pMO and THP-1 did not change upon NiV infection. Across TNF-α-treated endothelial monolayer, there was significant increase of almost twofold in migration of NiV-infected iDC and THP-1 over mock-infected cells. Immunofluorescence analysis showed the migrated NiV-infected leukocytes retained their ability to infect other cells. This study demonstrates for the first time that active NiV infection of iDC and THP-1 increased their transendothelial migration activity across HBMEC and activation of HBMEC by TNF-α further promoted migration. The findings suggest that NiV infection of leukocytes to disseminate the virus via the "Trojan horse" mechanism is a viable route of entry into the CNS.}, } @article {pmid30478736, year = {2019}, author = {Scheideler, M}, title = {Regulatory Small and Long Noncoding RNAs in Brite/Brown Adipose Tissue.}, journal = {Handbook of experimental pharmacology}, volume = {251}, number = {}, pages = {215-237}, doi = {10.1007/164_2018_123}, pmid = {30478736}, issn = {0171-2004}, mesh = {Adipocytes ; *Adipose Tissue, Brown/metabolism ; Energy Metabolism ; Humans ; Obesity ; *RNA, Long Noncoding ; Thermogenesis/*physiology ; }, abstract = {Brite/brown adipose tissue (BAT) is a thermogenic tissue able to dissipate energy via non-shivering thermogenesis. It is naturally activated by cold and has been demonstrated to increase thermogenic capacity, elevate energy expenditure, and to ultimately contribute to fat mass reduction. Thus, it emerges as novel therapeutic concept for pharmacological intervention in obesity and other metabolic disorders. Therefore, the comprehensive understanding of the regulatory network in thermogenic adipocytes is in demand.The surprising findings that (1) all human protein-coding genes make up not more than 2% of our genome, (2) organismal complexity goes well along with the percentage of nonprotein-coding sequences, and that (3) three quarters of our genome are pervasively transcribed, provide evidence that noncoding RNAs (ncRNAs) are not junk, but a significant and even predominant part of our transcriptome representing a treasure chest worth retrieving regulatory determinants in biological processes and diseases.In this chapter, the impact of regulatory small and long ncRNAs (lncRNAs) in particular microRNAs and lncRNAs on BAT formation and metabolic function and their involvement in physiological and pathological conditions has been reviewed.}, } @article {pmid30478507, year = {2019}, author = {Stadlbauer, A and Zimmermann, M and Bennani-Baiti, B and Helbich, TH and Baltzer, P and Clauser, P and Kapetas, P and Bago-Horvath, Z and Pinker, K}, title = {Development of a Non-invasive Assessment of Hypoxia and Neovascularization with Magnetic Resonance Imaging in Benign and Malignant Breast Tumors: Initial Results.}, journal = {Molecular imaging and biology}, volume = {21}, number = {4}, pages = {758-770}, pmid = {30478507}, issn = {1860-2002}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*blood supply/*diagnostic imaging/pathology ; Female ; Humans ; Linear Models ; *Magnetic Resonance Imaging ; Middle Aged ; Neovascularization, Pathologic/*diagnostic imaging ; Oxygen/metabolism ; *Tumor Hypoxia ; Young Adult ; }, abstract = {PURPOSE: To develop a novel magnetic resonance imaging (MRI) approach for the noninvasive assessment of hypoxia and neovascularization in breast tumors.

PROCEDURES: In this IRB-approved prospective study, 20 patients with suspicious breast lesions (BI-RADS 4/5) underwent multiparametric breast MRI including quantitative BOLD (qBOLD) and vascular architecture mapping (VAM). Custom-made in-house MatLab software was used for qBOLD and VAM data postprocessing and calculation of quantitative MRI biomarker maps of oxygen extraction fraction (OEF), metabolic rate of oxygen (MRO2), and mitochondrial oxygen tension (mitoPO2) to measure tissue hypoxia and neovascularization including vascular architecture including microvessel radius (VSI), density (MVD), and type (MTI). Histopathology was used as standard of reference. Appropriate statistics were performed to assess and compare correlations between MRI biomarkers for hypoxia and neovascularization.

RESULTS: qBOLD and VAM data with good quality were obtained from all patients with 13 invasive ductal carcinoma (IDC) and 7 benign breast tumors with a lesion diameter of at least 10 mm in all spatial directions. MRI biomarker maps of oxygen metabolism and neovascularization demonstrated intratumoral spatial heterogeneity with a broad range of biomarker values. Bulk tumor neovasculature consisted of draining venous microvasculature with slow flowing blood. High OEF and low mitoPO2 were associated with low MVD and vice versa. The heterogeneous pattern of MRO2 values showed spatial congruence with VSI. IDCs showed significantly higher MRO2 (P = 0.007), lower mitoPO2 (P = 0.021), higher MVD (P = 0.005), and lower (i.e., more pathologic) MTI (P = 0.001) compared with benign breast tumors. These results indicate that IDCs consume more oxygen and are more hypoxic and neovascularized than benign tumors.

CONCLUSIONS: We developed a novel MRI approach for the noninvasive assessment of hypoxia and neovascularization in benign and malignant breast tumors that can be easily integrated in a diagnostic MRI protocol and provides insight into intratumoral heterogeneity.}, } @article {pmid30477882, year = {2019}, author = {Egevad, L and Judge, M and Delahunt, B and Humphrey, PA and Kristiansen, G and Oxley, J and Rasiah, K and Takahashi, H and Trpkov, K and Varma, M and Wheeler, TM and Zhou, M and Srigley, JR and Kench, JG}, title = {Dataset for the reporting of prostate carcinoma in core needle biopsy and transurethral resection and enucleation specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR).}, journal = {Pathology}, volume = {51}, number = {1}, pages = {11-20}, doi = {10.1016/j.pathol.2018.10.003}, pmid = {30477882}, issn = {1465-3931}, mesh = {Adenocarcinoma/*pathology/surgery ; Biopsy, Large-Core Needle ; Humans ; Male ; Neoplasm Grading ; Prostate/*pathology/surgery ; Prostatectomy/methods ; Prostatic Neoplasms/*pathology/surgery ; }, abstract = {The International Collaboration on Cancer Reporting (ICCR) is a project which issues datasets and guidelines for international standardisation of cancer reporting. This review summarises the required and recommended elements of the datasets for prostate core needle biopsies and transurethral resection (TURP) and enucleation specimens of the prostate. To obtain as much information as possible from needle biopsies there should be only one core in each specimen jar with the exception of saturation biopsies. The gross description of the specimens should include core lengths of needle biopsies and weight of resection specimens. The tumours should be classified according to the 4th World Health Organization (WHO) classification and graded both by Gleason scores and the grouping of these in International Society of Urological Pathology (ISUP) grades (Grade groups). Percent high-grade cancer is an optional component of the report. Tumour extent in needle biopsies should be reported both by number of cores positive for cancer and the linear extent measured in either millimetre or percent core involvement by tumour. In needle biopsies where low-grade cancer is discontinuous and seen in few cores, it is recommended that the tumour extent should be reported both by including and subtracting intervening benign tissue. For resection specimens, the percentage of the tissue area (or percentage of number of TURP chips) involved with cancer should be estimated. Extraprostatic extension should be reported when seen, while the reporting of perineural, seminal vesicle/ejaculatory duct and lymphovascular invasion is only recommended. Intraductal carcinoma of the prostate (IDC-P) should be reported when present, because of its strong link with aggressive cancer. The current recommendation is that the IDC-P component should not be graded. The structured and standardised reporting of prostate cancer contributes to safer and more efficient patient care and facilitates the compilation and understanding of multiparametric diagnostic and prognostic data.}, } @article {pmid30474859, year = {2019}, author = {Oliver-Caldes, A and Gonzalez-Farre, B and Merino, A and Rozman, M}, title = {Carcinocythaemia in an advanced stage of invasive ductal carcinoma of the breast.}, journal = {British journal of haematology}, volume = {185}, number = {1}, pages = {8}, doi = {10.1111/bjh.15678}, pmid = {30474859}, issn = {1365-2141}, mesh = {Aged ; Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers ; Biopsy ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Female ; Humans ; Immunohistochemistry ; Leukocyte Count ; Neoplasm Grading ; Neoplasm Staging ; Neoplastic Cells, Circulating/metabolism/pathology ; }, } @article {pmid30470306, year = {2018}, author = {Schmidt, SF and Rohm, M and Herzig, S and Berriel Diaz, M}, title = {Cancer Cachexia: More Than Skeletal Muscle Wasting.}, journal = {Trends in cancer}, volume = {4}, number = {12}, pages = {849-860}, doi = {10.1016/j.trecan.2018.10.001}, pmid = {30470306}, issn = {2405-8025}, mesh = {Antineoplastic Agents/pharmacology/*therapeutic use ; Cachexia/etiology/mortality/*physiopathology/prevention & control ; Combined Modality Therapy/methods ; Humans ; Muscle, Skeletal/physiopathology ; Neoplasms/*complications/drug therapy/mortality/physiopathology ; Nutritional Support/*methods ; Paraneoplastic Syndromes/etiology/mortality/*physiopathology/prevention & control ; Quality of Life ; Treatment Outcome ; }, abstract = {Cancer cachexia is a multifactorial condition characterized by body weight loss that negatively affects quality of life and survival of patients with cancer. Despite the clinical relevance, there is currently no defined standard of care to effectively counteract cancer-associated progressive tissue wasting. Skeletal muscle atrophy represents the main manifestation of cancer cachexia. However, cancer cachexia is increasingly seen as a systemic phenomenon affecting and/or influenced by various organs. Here, we describe recent developments elucidating the roles of different tissues as well as tissue crosstalk in this wasting syndrome, including potential links to other cancer-associated morbidities. A more comprehensive understanding of cancer cachexia etiology and heterogeneity may enable the development of intervention strategies to prevent or reverse this devastating condition.}, } @article {pmid30464099, year = {2018}, author = {Koori, N and Kurata, K and Nihashi, T and Noda, S and Mashita, Y}, title = {[Comparison of Kinetic Curve between Gadodiamide Hydrate and Gadobutrol on Breast Dynamic Contrast-enhanced Magnetic Resonance Imaging in Invasive Ductal Carcinoma].}, journal = {Nihon Hoshasen Gijutsu Gakkai zasshi}, volume = {74}, number = {11}, pages = {1313-1318}, doi = {10.6009/jjrt.2018_JSRT_74.11.1313}, pmid = {30464099}, issn = {0369-4305}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal/diagnostic imaging ; Contrast Media/administration & dosage ; Female ; Gadolinium DTPA/administration & dosage ; Humans ; *Magnetic Resonance Imaging ; Organometallic Compounds/administration & dosage ; }, abstract = {The shape of the kinetic curve for gadobutrol is reportedly different compared with that for other conventional contrast agents. We speculate that the shape of gadobutrol kinetic curve may be influenced by different magnetic resonance imaging (MRI) protocols and evaluation methods. The purpose of our study was to assess the influence between gadobutrol and other conventional contrast agent (gadodiamide hydrate) on the kinetic curve in invasive ductal carcinoma (IDC). We assessed 139 women of IDC in this study. Gadodiamide hydrate (2 ml/s) was administered to 69 women, and gadobutrol (1 ml/s) was administrated to 70 women, both contrast agents at 0.1 mmol/kg BW. When the kinetic curves of contrast agents were evaluated between by Breast Imaging Reporting and Data System (BI-RADS) 4th edition and BI-RADS 5th edition, suggested that the analysis method of BI-RADS may affect. Patient group who were administered gadobutrol demonstrated a lower washout rate when compared with patient group who were administered gadodiamide hydrate administration (P<0.01). These results suggest that the kinetic curve characteristics of gadobutrol are an important consideration in diagnosis. Therefore, it is necessary to perform image diagnosis by considering the influence of the contrast agent and the analysis method, when image diagnostic doctor perform image diagnosis.}, } @article {pmid30448710, year = {2019}, author = {Cho, WK and Choi, DH and Kim, H and Noh, JM and Park, W and Cha, H}, title = {Adjuvant radiation therapy in small ductal carcinoma in situ.}, journal = {Breast (Edinburgh, Scotland)}, volume = {43}, number = {}, pages = {55-58}, doi = {10.1016/j.breast.2018.11.004}, pmid = {30448710}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy ; Female ; Humans ; Margins of Excision ; *Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/*epidemiology ; Radiotherapy, Adjuvant ; Tumor Burden ; Young Adult ; }, abstract = {BACKGROUND: The objective of this study was to evaluate ipsilateral breast tumor recurrence (IBTR) rates in patients with small (≤1 cm) ductal carcinoma in situ (DCIS) who were followed up for more than 15 years.

METHODS: We identified 209 patients with primary small (≤1 cm) DCIS without invasion who received curative excision with and without adjuvant radiation therapy (RT) from 1996 to 2009. IBTR rates and prognostic factors in all patients were estimated by univariate and multivariate analyses.

RESULTS: With a median follow-up of 104 months, eight (53.3%) had DCIS recurrence and seven (46.7%) had recurrence of invasive ductal carcinoma. IBTR rate of all patients was 7.5% at 10 years and 12.1% at 15 years. In univariate analysis, age and subtypes were significant factors for IBTR. In multivariate analysis, resection margin, adjuvant RT, and endocrine therapy were significant factors for IBTR.

CONCLUSIONS: IBTR rate of small (≤1 cm) DCIS following excision with or without adjuvant RT was 12.1% at 15 years. Adjuvant RT and endocrine therapy were associated with lower IBTR rate in small DCIS.}, } @article {pmid30439625, year = {2019}, author = {Tawara, K and Scott, H and Emathinger, J and Ide, A and Fox, R and Greiner, D and LaJoie, D and Hedeen, D and Nandakumar, M and Oler, AJ and Holzer, R and Jorcyk, C}, title = {Co-Expression of VEGF and IL-6 Family Cytokines is Associated with Decreased Survival in HER2 Negative Breast Cancer Patients: Subtype-Specific IL-6 Family Cytokine-Mediated VEGF Secretion.}, journal = {Translational oncology}, volume = {12}, number = {2}, pages = {245-255}, pmid = {30439625}, issn = {1936-5233}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; }, abstract = {Breast cancer cell-response to inflammatory cytokines such as interleukin-6 (IL-6) and oncostatin M (OSM) may affect the course of clinical disease in a cancer subtype-dependent manner. Furthermore, vascular endothelial growth factor A (VEGF) secretion induced by IL-6 and OSM may also be subtype-dependent. Utilizing datasets from Oncomine, we show that poor survival of invasive ductal carcinoma (IDC) breast cancer patients is correlated with both high VEGF expression and high cytokine or cytokine receptor expression in tumors. Importantly, epidermal growth factor receptor-negative (HER2-), but not HER2-positive (HER2+), patient survival is significantly lower with high tumor co-expression of VEGF and OSM, OSMRβ, IL-6, or IL-6Rα compared to low co-expression. Furthermore, assessment of HER2- breast cancer cells in vitro identified unique signaling differences regulating cytokine-induced VEGF secretion. The levels of VEGF secretion were analyzed by ELISA with siRNAs for hypoxia inducible factor 1 α (HIF1α) and signal transducer and activator of transcription 3 (STAT3). Specifically, we found that estrogen receptor-negative (ER-) MDA-MB-231 cells respond only to OSM through STAT3 signaling, while ER+ T47D cells respond to both OSM and IL-6, though to IL-6 to a lesser extent. Additionally, in the ER+ T47D cells, OSM signals through both STAT3 and HIF1α. These results highlight that the survival of breast cancer patients with high co-expression of VEGF and IL-6 family cytokines is dependent on breast cancer subtype. Thus, the heterogeneity of human breast cancer in relation to IL-6 family cytokines and VEGF may have important implications in clinical treatment options, disease progression, and ultimately patient prognosis.}, } @article {pmid30425580, year = {2018}, author = {Ren, K and Yin, Y and He, F and Shao, Y and Wang, S}, title = {Prognostic role of derived neutrophil-to-lymphocyte ratio in surgical triple-negative breast cancer.}, journal = {Cancer management and research}, volume = {10}, number = {}, pages = {4891-4898}, pmid = {30425580}, issn = {1179-1322}, abstract = {INTRODUCTION: The role of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of patients with triple-negative breast cancer (TNBC) has not been well studied. Here, we attempted to investigate the significance of dNLR in predicting the prognosis of patients with surgical (nonmetastatic) TNBC.

METHODS: A total of 281 patients diagnosed with surgical TNBC in The First Affiliated Hospital of University of Science and Technology of China from February 2005 to March 2015 were retrospectively included in this study. Kaplan-Meier curve analysis was used to assess the disease-free survival (DFS) and overall survival (OS). We used Cox regression model to assess the prognostic significance of pretreatment dNLR and other clinicopathological parameters in TNBC patients.

RESULTS: The median DFS in TNBC patients who had low dNLR and high dNLR was 28.9 and 15.1 months (P<0.001), respectively, whereas the median OS in patients who had low dNLR and high dNLR was 71.2 and 42.3 months (P<0.001), respectively. In patients aged ≤50 years and with invasive ductal carcinoma, a low dNLR predicted better DFS and OS compared with a high dNLR. Multivariate analysis demonstrated that the increased dNLR was a risk factor of poor DFS (HR=1.90, 95% CI: 1.52-2.46, P=0.007) and OS (HR=2.56, 95% CI: 1.69-3.58, P=0.001).

CONCLUSION: Pretreatment dNLR is an independent factor of prognosis for TNBC patients, which potentially allows clinical doctors to improve outcomes of patients with high dNLR by treating with aggressive therapy, such as high-dose adjuvant chemotherapy and radiotherapy.}, } @article {pmid30423570, year = {2019}, author = {Badr, NM and Roberts, C and Shaaban, AM}, title = {Extramedullary Haematopoiesis in Axillary Lymph Nodes of Breast Carcinoma Patients Receiving Neoadjuvant Chemotherapy: A Potential Diagnostic Pitfall.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {86}, number = {2-3}, pages = {167-172}, doi = {10.1159/000493752}, pmid = {30423570}, issn = {1423-0291}, mesh = {Aged ; Axilla/pathology ; Breast/pathology ; Breast Neoplasms/diagnosis/*drug therapy/pathology ; Carcinoma, Ductal, Breast/diagnosis/*drug therapy/pathology ; Female ; *Hematopoiesis, Extramedullary ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis/diagnosis ; Mastectomy, Segmental ; *Neoadjuvant Therapy ; Remission Induction ; }, abstract = {Extramedullary haematopoiesis (EMH) in the axillary lymph node of breast cancer patients is extremely rare but when encountered can represent a diagnostic challenge. We aim to highlight this incidental finding as a diagnostic pitfall which can be mistaken for metastatic carcinoma (particularly of the metaplastic type). We report the case of a 68-year-old Caucasian female with a family history of cancer. Core biopsy revealed that she had grade II oestrogen receptor-negative, Her2-positive invasive ductal carcinoma. She was offered neoadjuvant chemotherapy with Herceptin and subsequently underwent breast-conserving surgery. Microscopic examination of the post-treatment breast surgical specimen showed a partial pathological response with large areas of tumour regression. The sentinel lymph node showed frequent large single and multinucleate giant cells with hyperchromatic nuclei located predominantly within the subcapsular and medullary sinuses. The morphological differentials of metastatic carcinoma, sinus histiocytosis and extramedullary haematopoiesis were considered. A panel of immunohistochemistry showed these large cells to be negative for epithelial markers and CD68. They were strongly positive for CD42b (megakaryocyte marker). Smaller myeloperoxidase and factor VIII-positive cells were identified. The findings confirmed EMH. Sentinel nodes are often well scrutinised by pathologists for evidence of metastatic carcinoma as an important prognostic parameter both in the standard and neoadjuvant setting. Nodal megakaryocytes have been described in response to neoadjuvant chemotherapy particularly in association with Herceptin treatment. Pathologists' awareness of this finding in the neoadjuvant setting is crucial to avoid a mistaken diagnosis of malignancy. A relevant immunohistochemical panel together with careful attention to morphology should help establish the correct diagnosis.}, } @article {pmid30423024, year = {2019}, author = {Sokol, ES and Feng, YX and Jin, DX and Basudan, A and Lee, AV and Atkinson, JM and Chen, J and Stephens, PJ and Frampton, GM and Gupta, PB and Ross, JS and Chung, JH and Oesterreich, S and Ali, SM and Hartmaier, RJ}, title = {Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {1}, pages = {115-123}, pmid = {30423024}, issn = {1569-8041}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*secondary ; Carcinoma, Lobular/drug therapy/genetics/*secondary ; Drug Resistance, Neoplasm/*genetics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neurofibromin 1/*genetics ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed.

PATIENTS AND METHODS: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes.

RESULTS: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%).

CONCLUSIONS: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.}, } @article {pmid30421661, year = {2019}, author = {Peters, AS and Wortmann, M and Fleming, TH and Nawroth, PP and Bruckner, T and Böckler, D and Hakimi, M}, title = {Effect of metformin treatment in patients with type 2 diabetes with respect to glyoxalase 1 activity in atherosclerotic lesions.}, journal = {VASA. Zeitschrift fur Gefasskrankheiten}, volume = {48}, number = {2}, pages = {186-192}, doi = {10.1024/0301-1526/a000762}, pmid = {30421661}, issn = {0301-1526}, mesh = {Aged ; *Atherosclerosis ; *Diabetes Mellitus, Type 2/drug therapy ; Female ; Humans ; Lactoylglutathione Lyase ; Male ; Metformin/*therapeutic use ; Respect ; }, abstract = {BACKGROUND: The enzyme glyoxalase1 (GLO1) is the main opponent in the degradation of the reactive metabolite methylglyoxal (MG), which by glycation of macromolecules is involved in atherogenesis. Reduced GLO1-activity in atherosclerotic tissue is known to be associated with diabetes. It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells. The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes.

PATIENTS AND METHODS: Patients with type 2 diabetes and carotid artery disease were included into the study prospectively. Type of diabetes-medication was documented upon admission along with demographic and clinical history. Using shock frozen endarterectomy-derived carotid artery plaques, GLO1-activity as well as protein expression was measured by a spectophotometric assay and western-blotting respectively.

RESULTS: 33 patients (76 % male, mean age 71 years) were included into the study and were divided according to treatment with metformin or not (15 vs. 18 patients). GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056). Normalisation of GLO1-activity onto GLO1-expression level lead to a significant increase by more than twofold (8.48 vs. 3.85, p = 0.044) while GLO1-protein levels did not differ significantly. GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment.

CONCLUSIONS: Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions. Regarding the macro- and microvascular complications in these patients further studies are needed to gain more insight into the effect of metformin on the GLO/MG system.}, } @article {pmid30412075, year = {2018}, author = {Lee, SJ and Chung, MS and Shin, SJ and Choi, YY}, title = {Correlation of tumor uptake on breast-specific gamma imaging and fluorodeoxyglucose PET/CT with molecular subtypes of breast cancer.}, journal = {Medicine}, volume = {97}, number = {43}, pages = {e12840}, pmid = {30412075}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Female ; Fluorodeoxyglucose F18/*pharmacology ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; Radiopharmaceuticals/pharmacology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; }, abstract = {Mechanisms of technetium-99m sesta-methoxyisobutylisonitrile (sestamibi) and F-fluorodeoxyglucose (FDG) uptake by tumor are different. The purpose of this study was to investigate the association between the tumor uptake of these 2 tracers in invasive ductal carcinoma and to examine thecorrelation of uptake of each tracer with prognostic factors and tumor molecular subtypes.A total of 96 patients with invasive ductal carcinoma who underwent preoperative breast-specific gamma imaging and FDG positron-emission tomography/computed tomography were retrospectively enrolled. Tumor-to-background ratio (TBR) of sestamibi and maximum standardized uptake value (SUVmax) of FDG were correlated with each other. Each of them was then compared with prognostic factors and molecular subtypes.In all tumors, there was a moderate positive correlation between TBR and SUVmax (r = 0.520, P < .001). Both TBR and SUVmax were significantly correlated with tumor size, incidence of axillary lymph node metastasis, histologic grade, estrogen receptor, progesterone receptor status, and Ki-67.There is a moderate degree of association between TBR of sestamibi and SUVmax of FDG in the invasive breast cancer. Two imaging indexes showed the similar tendency related with prognostic factors and molecular subtypes. While both TBR and SUVmax were significantly different between luminal A and nonluminal A tumors, neither of them had high enough sensitivity or specificity to obviate pathologic and molecular diagnosis.}, } @article {pmid30411613, year = {2018}, author = {Huang, B and Zhao, F and Fishman, T and Chen, WQ and Heeren, N and Hertwich, EG}, title = {Building Material Use and Associated Environmental Impacts in China 2000-2015.}, journal = {Environmental science & technology}, volume = {52}, number = {23}, pages = {14006-14014}, doi = {10.1021/acs.est.8b04104}, pmid = {30411613}, issn = {1520-5851}, mesh = {China ; *Construction Materials ; Environment ; Global Warming ; *Greenhouse Gases ; Humans ; }, abstract = {A rapidly increasing use of building materials poses threats to resources and the environment. Using novel, localized life cycle inventories and building material intensity data, this study quantifies the resource use of building materials in mainland China and evaluates their embodied environmental impacts. Newly built floor area and related material consumption grew 11% per annum from 2000 to 2015, leveling off at the end of this period. Concrete, sand, gravel, brick, and cement were the main materials used. Spatially, construction activities expanded from east China into the central part of the country. Cement, steel, and concrete production are the key contributors to associated environmental impacts, e.g., cement and steel each account for around 25% of the global warming potential from building materials. Building materials contribute considerably to the impact categories of human toxicity, fossil depletion, and global warming, emphasizing that greenhouse gas emissions should not be the sole focus of research on environmental impacts of building materials. These findings quantitatively shed light on the urgent need to reduce environmental impacts and to conserve energy in the manufacturing processes of building materials on the national scale.}, } @article {pmid30409703, year = {2019}, author = {Wolff, G and Taranko, AE and Meln, I and Weinmann, J and Sijmonsma, T and Lerch, S and Heide, D and Billeter, AT and Tews, D and Krunic, D and Fischer-Posovszky, P and Müller-Stich, BP and Herzig, S and Grimm, D and Heikenwälder, M and Kao, WW and Vegiopoulos, A}, title = {Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.}, journal = {Molecular metabolism}, volume = {19}, number = {}, pages = {97-106}, pmid = {30409703}, issn = {2212-8778}, mesh = {Adipocytes/metabolism ; Adipose Tissue/metabolism ; Adipose Tissue, White/metabolism ; Adiposity/drug effects ; Adult ; Animals ; Diet, High-Fat ; Extracellular Matrix/metabolism ; Female ; Glucose/*metabolism ; Homeostasis ; Humans ; Insulin Resistance ; Intra-Abdominal Fat/metabolism ; Liver/metabolism ; Lumican/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/*metabolism ; Proteoglycans/metabolism ; }, abstract = {OBJECTIVE: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.

METHODS: Whole body ablation of Lumican (Lum[-/-]) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.

RESULTS: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.

CONCLUSIONS: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome.}, } @article {pmid30409127, year = {2018}, author = {Ye, FG and Xia, C and Ma, D and Lin, PY and Hu, X and Shao, ZM}, title = {Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {1085}, pmid = {30409127}, issn = {1471-2407}, support = {MOST2016YFC0900300//Ministry of Science and Technology of the People's Republic of China/ ; 81672601//National Natural Science Foundation of China (CN)/ ; 15410724000//Shanghai Committee of Science and Technology Funds/ ; }, mesh = {Aged ; Axilla/pathology ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Papillary/*epidemiology/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nomograms ; Odds Ratio ; Population Surveillance ; Preoperative Period ; ROC Curve ; Reproducibility of Results ; Risk Factors ; SEER Program ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.

METHODS: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.

RESULTS: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).

CONCLUSIONS: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.}, } @article {pmid30407355, year = {2018}, author = {Liu, A and Feng, Y and Chen, B and Li, L and Wu, D and Qian, J and Yang, A}, title = {A case report of metastatic breast cancer initially presenting with esophageal dysphagia.}, journal = {Medicine}, volume = {97}, number = {45}, pages = {e13184}, pmid = {30407355}, issn = {1536-5964}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Deglutition Disorders/*etiology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Esophageal Neoplasms/*secondary/therapy ; Esophagectomy/methods ; Esophagus/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.

PATIENT CONCERNS: A 62-year-old woman was admitted to our hospital for progressive dysphagia.

DIAGNOSES: Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.

INTERVENTIONS: The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.

OUTCOMES: The patient remained symptom-free during 5 months of follow-up examinations.

LESSONS: This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.}, } @article {pmid30406220, year = {2017}, author = {Cheng, C and Thakur, R and Nair, AR and Sterrett, S and Fridman, G}, title = {Miniature Elastomeric Valve Design for Safe Direct Current Stimulator.}, journal = {IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference}, volume = {2017}, number = {}, pages = {1-4}, pmid = {30406220}, support = {R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {For safety reasons, commercial neural implants use charge-balanced biphasic pulses to interact with target neurons using metal electrodes. Short biphasic pulses are used to avoid irreversible electrochemical reactions at the electrode-tissue interfaces. Biphasic pulses are effective at exciting neurons, but quite limited in inhibiting their activity. In contrast, direct current can both excite and inhibit neurons, however delivered to metal electrodes, it causes toxic electrochemical reactions. We recently introduced Safe Direct Current Stimulator (SDCS) technology, which can excite or inhibit neurons without violating the safety criteria. Instead of direct current, SDCS generates an ionic direct current (iDC) from a biphasic input signal using a network of fluidic channels and mechanical valves. A key enabler towards transforming SDCS concept from a benchtop design to an implantable neural prosthesis is the design of a miniature valve. In this work, we present poly-dimethylsiloxane (PDMS) based elastomeric valves, squeeze valve (SV) and plunger valve (PV) capable of being actuated using a shape memory alloy wire.}, } @article {pmid30406219, year = {2017}, author = {Ou, P and Fridman, G}, title = {Electronics for a Safe Direct Current Stimulator.}, journal = {IEEE Biomedical Circuits and Systems Conference : healthcare technology : [proceedings]. IEEE Biomedical Circuits and Systems Conference}, volume = {2017}, number = {}, pages = {}, pmid = {30406219}, support = {R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, abstract = {Commercially available neuroprostheses, while successful and effective, are limited in their functionality by their reliance on pulsatile stimulation. Direct current (DC) has been shown to have great potential for the purposes of neuromodulation; however, direct current cannot be applied directly to neurons due to the charge injection thresholds of electrodes. We are developing a Safe Direct Current Stimulator (SDCS) that applies ionic direct current (iDC) without inducing toxic electrochemical reactions. The current design of the SDCS uses a series of eight valves in conjunction with four electrodes to rectify ionic current in microfluidic channels. This paper outlines the design, implementation, and testing of the electronics of the SDCS. These electronics will ultimately be interfaced with a separate microfluidic circuit in the device prototype. Testing the outputs of the electronics confirmed adherence to its design requirements. The completion of the SDCS electronics enables the further development of iDC as a mechanism for neuromodulation.}, } @article {pmid30402704, year = {2019}, author = {Xie, T and Zhao, Q and Fu, C and Bai, Q and Zhou, X and Li, L and Grimm, R and Liu, L and Gu, Y and Peng, W}, title = {Differentiation of triple-negative breast cancer from other subtypes through whole-tumor histogram analysis on multiparametric MR imaging.}, journal = {European radiology}, volume = {29}, number = {5}, pages = {2535-2544}, pmid = {30402704}, issn = {1432-1084}, support = {61731008//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; ROC Curve ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; Young Adult ; }, abstract = {PURPOSE: To identify triple-negative (TN) breast cancer imaging biomarkers in comparison to other molecular subtypes using multiparametric MR imaging maps and whole-tumor histogram analysis.

MATERIALS AND METHODS: This retrospective study included 134 patients with invasive ductal carcinoma. Whole-tumor histogram-based texture features were extracted from a quantitative ADC map and DCE semi-quantitative maps (washin and washout). Univariate analysis using the Student's t test or Mann-Whitney U test was performed to identify significant variables for differentiating TN cancer from other subtypes. The ROC curves were generated based on the significant variables identified from the univariate analysis. The AUC, sensitivity, and specificity for subtype differentiation were reported.

RESULTS: The significant parameters on the univariate analysis achieved an AUC of 0.710 (95% confidence interval [CI] 0.562, 0.858) with a sensitivity of 63.6% and a specificity of 73.1% at the best cutoff point for differentiating TN cancers from Luminal A cancers. An AUC of 0.763 (95% CI 0.608, 0.917) with a sensitivity of 86.4% and a specificity of 72.2% was achieved for differentiating TN cancers from human epidermal growth factor receptor 2 (HER2) positive cancers. Also, an AUC of 0.683 (95% CI 0.556, 0.809) with a sensitivity of 54.5% and a specificity of 83.9% was achieved for differentiating TN cancers from non-TN cancers. There was no significant feature on the univariate analysis for TN cancers versus Luminal B cancers.

CONCLUSIONS: Whole-tumor histogram-based imaging features derived from ADC, along with washin and washout maps, provide a non-invasive analytical approach for discriminating TN cancers from other subtypes.

KEY POINTS: • Whole-tumor histogram-based features on MR multiparametric maps can help to assess biological characterization of breast cancer. • Histogram-based texture analysis may predict the molecular subtypes of breast cancer. • Combined DWI and DCE evaluation helps to identify triple-negative breast cancer.}, } @article {pmid30402219, year = {2018}, author = {Garcia-Hernandez, I and Lopez-Garcia, CA and Cardona-Huerta, S and Ortiz-Lopez, R and Tamez Salazar, JJ and Canavati Marcos, M and Esteban-Zubero, E and Verdin Gonzalez, D and Monroig-Bosque, PDC and Gomez-Macias, GS}, title = {A solitary presentation of panniculitis in a patient with a history of breast cancer.}, journal = {Annals of medicine and surgery (2012)}, volume = {36}, number = {}, pages = {54-57}, pmid = {30402219}, issn = {2049-0801}, abstract = {INTRODUCTION: Panniculits presents as an inflammation of the subcutaneous adipose tissue of the skin. In breast, panniculitis is very rare and is usually a manifestation of underlying inflammatory conditions. The typical presentation is palpable tender nodules, which in cases of breast panniculitis, triggers an extensive work up to exclude a malignancy. Herein we present a case of septal and lobar panniculitis in a female with clinical history of invasive ductal carcinoma.

PRESENTATION OF THE CASE: A 52-year old female with past medical history of invasive breast carcinoma 5 years prior to the presentation. The patient's chief complaint was a 1-year history of a subcutaneous nodular lesion on her left breast. A core biopsy of the firm nodule showed marked inflammation of the breast. A second skin biopsy showed an abundant chronic inflammatory infiltrate, with lymphocytic vasculitis and neuritis, suggestive of an underlying autoimmune process.

DISCUSSION: Subcutaneous panniculitis with or without vasculitis is a rare condition when presenting in the breast. Panniculitis can mimic malignancy and thus, it is important to differentially diagnose it from breast carcinoma. Histologically, it is classified in lobular and septal lymphocytic panniculitis depending on specific diagnostic characteristics.

CONCLUSION: Panniculitis of the breast is a rare condition that needs to be included in the differential diagnosis of subcutaneous breast masses. In all cases, but specifically in females with history of breast cancer, panniculitis still should be thought of as a possibility, and imaging as well as other diagnostic techniques can aid in making the correct diagnosis.}, } @article {pmid30400820, year = {2018}, author = {Suchanski, J and Grzegrzolka, J and Owczarek, T and Pasikowski, P and Piotrowska, A and Kocbach, B and Nowak, A and Dziegiel, P and Wojnar, A and Ugorski, M}, title = {Sulfatide decreases the resistance to stress-induced apoptosis and increases P-selectin-mediated adhesion: a two-edged sword in breast cancer progression.}, journal = {Breast cancer research : BCR}, volume = {20}, number = {1}, pages = {133}, pmid = {30400820}, issn = {1465-542X}, mesh = {Animals ; Apoptosis/drug effects/physiology ; Breast/*pathology ; Breast Neoplasms/*pathology ; Cell Adhesion/physiology ; Cell Hypoxia/physiology ; Cell Line, Tumor ; Disease Progression ; Doxorubicin/pharmacology ; Female ; Galactosylceramides/metabolism ; Humans ; Mice ; Mice, Nude ; Middle Aged ; P-Selectin/*metabolism ; Sulfoglycosphingolipids/*metabolism ; Sulfotransferases ; Sulfurtransferases/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: We have previously shown that galactosylceramide (GalCer) affects the tumourigenic and metastatic properties of breast cancer cells by acting as an anti-apoptotic molecule. Since GalCer is a precursor molecule in the synthesis of sulfatides, the present study was aimed to define the role of sulfatides in apoptosis and breast cancer progression.

METHODS: Expression of GAL3ST1 in breast cancer cell lines and breast cancer tissue specimens was analysed using real-time PCR, western blotting and immunohistochemistry analysis. The amount of sulfatide, GalCer and ceramide was analysed by thin-layer chromatography binding assay and by the modified hydrophilic interaction liquid chromatography coupled with electrospray mass spectrometry methodology. The tumourigenicity of cancer cells was analysed by an in-vivo tumour growth assay. Apoptotic cells were detected based on caspase-3 activation and the TUNEL assay. The interaction of breast cancer cells with P-selectin or E-selectin was analysed using the flow adhesion assay. The ability of sulfatide-expressing cells to activate and aggregate platelets was studied using the flow-cytometry-based aggregation assay.

RESULTS: Using two models of breast cancer, T47D cells with blocked synthesis of sulfatide and MDA-MB-231 cells with neosynthesis of this glycosphingolipid, we showed that high sulfatide levels resulted in increased sensitivity of cancer cells to apoptosis induced by hypoxia and doxorubicin in vitro, and decreased their tumourigenicity after transplantation into athymic nu/nu mice. Accordingly, a clinical study on GAL3ST1 expression in invasive ductal carcinoma revealed that its elevated level is associated with better prognosis. Using MDA-MB-231 cells with neosynthesis of sulfatide we also showed that sulfatide is responsible for adhesion of breast cancer cells to P-selectin-expressing cells, including platelets. Sulfatide also acted as an activating molecule, increasing the expression of P-selectin.

CONCLUSIONS: This study demonstrates that increased synthesis of sulfatide sensitises cancer cells to microenvironmental stress factors such as hypoxia and anticancer drugs such as doxorubicin. However, sulfatide is probably not directly involved in apoptotic cascades, because its increased synthesis by GAL3ST1 decreased the amounts of its precursor, GalCer, a known anti-apoptotic molecule. On the other hand, our data support the view that sulfatides are malignancy-related adhesive molecules involved in activating and binding P-selectin-expressing platelets to breast cancer cells.}, } @article {pmid30393644, year = {2018}, author = {Torres, MF and Perez-Villa, F}, title = {Heart transplantation in patients with hypertrophic cardiomyopathy.}, journal = {Global cardiology science & practice}, volume = {2018}, number = {3}, pages = {32}, pmid = {30393644}, issn = {2305-7823}, } @article {pmid30390616, year = {2018}, author = {Higareda-Almaraz, JC and Karbiener, M and Giroud, M and Pauler, FM and Gerhalter, T and Herzig, S and Scheideler, M}, title = {Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {794}, pmid = {30390616}, issn = {1471-2164}, support = {FWF, P25729-B19//Austrian Science Fund/ ; }, mesh = {Adipocytes/drug effects/*metabolism ; Adipose Tissue, White/*cytology/metabolism ; Computational Biology/methods ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; *Gene Regulatory Networks ; *Genes, Immediate-Early ; Humans ; Metabolic Networks and Pathways ; Molecular Sequence Annotation ; Norepinephrine/*metabolism/pharmacology ; Signal Transduction ; Transcription, Genetic ; Transcriptome ; }, abstract = {BACKGROUND: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level.

RESULTS: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses.

CONCLUSIONS: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.}, } @article {pmid30390196, year = {2019}, author = {Liang, L and Williams, MD and Bell, D}, title = {Expression of PTEN, Androgen Receptor, HER2/neu, Cytokeratin 5/6, Estrogen Receptor-Beta, HMGA2, and PLAG1 in Salivary Duct Carcinoma.}, journal = {Head and neck pathology}, volume = {13}, number = {4}, pages = {529-534}, pmid = {30390196}, issn = {1936-0568}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/*diagnosis/metabolism/pathology ; DNA-Binding Proteins/analysis/biosynthesis ; Estrogen Receptor beta/analysis/biosynthesis ; Female ; HMGA2 Protein/analysis/biosynthesis ; Humans ; Keratin-5/analysis/biosynthesis ; Keratin-6/analysis/biosynthesis ; Male ; Middle Aged ; PTEN Phosphohydrolase/analysis/biosynthesis ; Receptor, ErbB-2/analysis/biosynthesis ; Receptors, Androgen/analysis/biosynthesis ; Salivary Gland Neoplasms/*diagnosis/metabolism/pathology ; }, abstract = {Salivary duct carcinoma (SDC) is an aggressive neoplasm that resembles high-grade invasive ductal carcinoma of the breast. It can develop de novo or from the malignant transformation of pleomorphic adenoma (PA). We performed immunohistochemical stains for phosphatase and tensin homologue [PTEN androgen receptor (AR)], HER2/neu, cytokeratin 5/6, estrogen receptor-beta, high-mobility group AT-hook 2 (HMGA2), and pleomorphic adenoma gene 1 (PLAG1) on tissue microarray samples of 75 SDCs and 31 adenocarcinomas, not otherwise specified (NOS). Our data showed the following in SDC samples: loss of PTEN was found in 17 of 60 (28.3%); AR was expressed in 43 of 62 (69.4%); HER2/neu was overexpressed in 25 of 58 (43.1%); cytokeratin 5/6 was expressed in 14 of 54 (25.9%); estrogen receptor-beta was expressed in 37 of 56 (66.1%); HMGA2 was expressed in 29 of 63 (46.0%); and PLAG1 was expressed in 0 of 62 (0%). In addition, there was no statistically significant difference in the age at onset between patients with HMGA2-positive SDCs (range 32-85 years; mean: 64.3 years; median: 64.5 years) and those with HMGA2-negative SDCs (range 41-79 years; mean: 62.5 years; median: 64.5 years). There was also no statistically significant difference in overall survival between patients with HMGA2-positive and HMGA2-negative SDCs (follow-up period range 3-201 months; mean: 49.8 months; median: 30 months). Among 10 patients with a definite PA component (SDC ex-PA), 6 were positive and 4 were negative for HMGA2. Our data were consistent with previous findings that AR and estrogen receptor-beta are expressed in most SDCs, whereas HER2/neu overexpression and loss of PTEN are expressed in a subset of SDCs. In our cohort of patients, HMGA2 was expressed in approximately half of SDCs. HMGA2 and PTEN are promising therapeutic targets for salivary gland tumors.}, } @article {pmid30388104, year = {2018}, author = {Golan, Y and Alhadeff, R and Glaser, F and Ganoth, A and Warshel, A and Assaraf, YG}, title = {Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.}, journal = {PLoS computational biology}, volume = {14}, number = {11}, pages = {e1006503}, pmid = {30388104}, issn = {1553-7358}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; R01 AI055926/AI/NIAID NIH HHS/United States ; }, mesh = {Cation Transport Proteins/genetics/*metabolism ; Computational Biology/methods ; Deficiency Diseases/metabolism/therapy ; Homeostasis ; Humans ; *Models, Theoretical ; Monte Carlo Method ; Mutagenesis, Site-Directed ; Permeability ; Zinc/deficiency/*metabolism ; }, abstract = {Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2. Zinc is an essential trace element with 10% of the proteins in the human proteome capable of zinc binding. Thus, zinc deficiency or impairment of zinc homeostasis disrupt key cellular functions. Mammalian zinc transport proceeds via two transporter families: ZnT and ZIP; however, little is known about the zinc permeation pathway through these transporters. As a step towards this end, we herein undertook comprehensive computational analyses employing multiscale techniques, focusing on the human zinc transporter ZnT2 and its bacterial homologue, YiiP. Energy calculations revealed a favorable pathway for zinc translocation via alternating access. We then identified key residues presumably involved in the passage of zinc ions through ZnT2 and YiiP, and functionally validated their role in zinc transport using site-directed mutagenesis of ZnT2 residues. Finally, we use a CG Monte Carlo simulation approach to sample the transition between the inward-facing and the outward-facing states. We present our structural models of the inward- and outward-facing conformations of ZnT2 as a blueprint prototype of the transporter conformations, including the putative permeation pathway and participating residues. The insights gained from this study may facilitate the delineation of the pathways of other zinc transporters, laying the foundations for the molecular basis underlying ion permeation. This may possibly facilitate the development of therapeutic interventions in pathological states associated with zinc deficiency and other disorders based on loss-of-function mutations in solute carriers.}, } @article {pmid30385093, year = {2019}, author = {Shee, K and Muller, KE and Marotti, J and Miller, TW and Wells, WA and Tsongalis, GJ}, title = {Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {956-965}, pmid = {30385093}, issn = {1525-2191}, support = {F30 CA216966/CA/NCI NIH HHS/United States ; R01 CA200994/CA/NCI NIH HHS/United States ; R01 CA211869/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness ; *Precision Medicine ; Prognosis ; }, abstract = {Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression-based assay with the potential to prevent overtreatment in low-risk disease.}, } @article {pmid30380804, year = {2018}, author = {Kretschmer, N and Deutsch, A and Durchschein, C and Rinner, B and Stallinger, A and Higareda-Almaraz, JC and Scheideler, M and Lohberger, B and Bauer, R}, title = {Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {11}, pages = {}, pmid = {30380804}, issn = {1420-3049}, support = {P27505//Austrian Science Fund/ ; }, mesh = {Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Gene Expression Regulation/drug effects ; Humans ; Melanoma/*drug therapy ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects ; Naphthoquinones/chemistry/*pharmacology ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; }, abstract = {Skin cancer is currently diagnosed as one in every three cancers. Melanoma, the most aggressive form of skin cancer, is responsible for 79% of skin cancer deaths and the incidence is rising faster than in any other solid tumor type. Previously, we have demonstrated that dimethylacrylshikonin (DMAS), isolated from the roots of Onosma paniculata (Boraginaceae), exhibited the lowest IC50 values against different tumor types out of several isolated shikonin derivatives. DMAS was especially cytotoxic towards melanoma cells and led to apoptosis and cell cycle arrest. In this study, we performed a comprehensive gene expression study to investigate the mechanism of action in more detail. Gene expression signature was compared to vehicle-treated WM164 control cells after 24 h of DMAS treatment; where 1192 distinct mRNAs could be identified as expressed in all replicates and 89 were at least 2-fold differentially expressed. DMAS favored catabolic processes and led in particular to p62 increase which is involved in cell growth, survival, and autophagy. More in-depth experiments revealed that DMAS led to autophagy, ROS generation, and loss of mitochondrial membrane potential in different melanoma cells. It has been reported that the induction of an autophagic cell death represents a highly effective approach in melanoma therapy.}, } @article {pmid30375925, year = {2019}, author = {Chen, Y and Panda, A and Pahwa, S and Hamilton, JI and Dastmalchian, S and McGivney, DF and Ma, D and Batesole, J and Seiberlich, N and Griswold, MA and Plecha, D and Gulani, V}, title = {Three-dimensional MR Fingerprinting for Quantitative Breast Imaging.}, journal = {Radiology}, volume = {290}, number = {1}, pages = {33-40}, pmid = {30375925}, issn = {1527-1315}, support = {R21 EB026764/EB/NIBIB NIH HHS/United States ; R01 EB017219/EB/NIBIB NIH HHS/United States ; R01 EB016728/EB/NIBIB NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; R01 DK098503/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Phantoms, Imaging ; Prospective Studies ; Young Adult ; }, abstract = {Purpose To develop a fast three-dimensional method for simultaneous T1 and T2 quantification for breast imaging by using MR fingerprinting. Materials and Methods In this prospective study, variable flip angles and magnetization preparation modules were applied to acquire MR fingerprinting data for each partition of a three-dimensional data set. A fast postprocessing method was implemented by using singular value decomposition. The proposed technique was first validated in phantoms and then applied to 15 healthy female participants (mean age, 24.2 years ± 5.1 [standard deviation]; range, 18-35 years) and 14 female participants with breast cancer (mean age, 55.4 years ± 8.8; range, 39-66 years) between March 2016 and April 2018. The sensitivity of the method to B1 field inhomogeneity was also evaluated by using the Bloch-Siegert method. Results Phantom results showed that accurate and volumetric T1 and T2 quantification was achieved by using the proposed technique. The acquisition time for three-dimensional quantitative maps with a spatial resolution of 1.6 × 1.6 × 3 mm[3] was approximately 6 minutes. For healthy participants, averaged T1 and T2 relaxation times for fibroglandular tissues at 3.0 T were 1256 msec ± 171 and 46 msec ± 7, respectively. Compared with normal breast tissues, higher T2 relaxation time (68 msec ± 13) was observed in invasive ductal carcinoma (P < .001), whereas no statistical difference was found in T1 relaxation time (1183 msec ± 256; P = .37). Conclusion A method was developed for breast imaging by using the MR fingerprinting technique, which allows simultaneous and volumetric quantification of T1 and T2 relaxation times for breast tissues. © RSNA, 2018 Online supplemental material is available for this article.}, } @article {pmid30375263, year = {2018}, author = {Talei, A and Tahmasebi, S and Akrami, M and Zangouri, V and Rezaianzadeh, A and Arasteh, P and Eghbali, T and Hosseini, S}, title = {The Shiraz Breast Cancer Registry (SBCR): study design and primary reports.}, journal = {Personalized medicine}, volume = {15}, number = {6}, pages = {471-479}, doi = {10.2217/pme-2018-0047}, pmid = {30375263}, issn = {1744-828X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*genetics ; Carcinoma, Ductal, Breast/epidemiology ; Female ; Humans ; Iran/epidemiology ; Male ; Middle Aged ; Neoplasm Staging ; Preliminary Data ; Prognosis ; Registries ; Research Design ; Young Adult ; }, abstract = {AIM: This is a description of the largest breast cancer (BC) registry in Iran, termed the Shiraz Breast Cancer Registry (SBCR).

METHODS: Data on baseline and clinical characteristics, socioeconomic status, imaging, physical examination, histopathology, treatment and prognosis have been recorded for each individual.

RESULTS: Overall, 5937 were included in the report. Mean age of first presentation was 49.05 ± 11.69 years. Mean tumor size was 2.78 ± 1.76 cm. Most patients had stage 2 (46.9%) and 3 (25.5%) BCs, respectively. Most common type of BC was invasive ductal carcinoma (83.3%), followed by medullary carcinoma (3.8%). Overall, 12.9% were triple negative (HER2-, ER- and PR-).

CONCLUSION: The study provides an overview on the status of BC's in Iran and a wide opportunity for future studies.}, } @article {pmid30374411, year = {2018}, author = {Stillman, MD and Hoffman, JM and Barber, JK and Williams, SR and Burns, SP}, title = {Urinary tract infections and bladder management over the first year after discharge from inpatient rehabilitation.}, journal = {Spinal cord series and cases}, volume = {4}, number = {}, pages = {92}, pmid = {30374411}, issn = {2058-6124}, abstract = {STUDY DESIGN: Secondary analysis of data from a prospective clinical trial of telephone counseling.

OBJECTIVES: To describe changes in bladder management and development of bladder-related complications in the first year after discharge from inpatient spinal cord injury (SCI) rehabilitation. To determine whether urinary tract infection (UTI) is associated with bladder management technique or severity of SCI during this time period.

SETTING: One SCI Model System center.

METHODS: Post hoc analysis of bladder-specific responses to a phone intervention meant to reduce secondary complications of paralysis in adults (n = 169) over the first year after discharge from initial inpatient rehabilitation (IR).

RESULTS: Bladder management was associated with injury level during and immediately after inpatient rehabilitation, and with American Spinal Injury Association (ASIA) Impairment Scale (AIS) score over the entire year. During one year of follow-up, 19% of patients changed bladder management techniques. Among participants performing intermittent catheterization (IC), 20% had urinary incontinence weekly or more frequently. The cumulative incidence of UTI was 71% by the end of the study, and between 27 and 46% of subjects reported UTIs during each 3-month period. Subjects with spontaneous voiding reported significantly fewer UTIs than those using IC or indwelling catheterization (IDC), but there was no significant difference in UTIs between IC and IDC.

CONCLUSION: During the first year following discharge, approximately one in five patients changed the bladder management technique and urinary incontinence occurred in a substantial proportion of those performing IC. These findings suggest a need for more frequent monitoring of bladder changes and complications over the first year after IR.}, } @article {pmid30372658, year = {2019}, author = {Steger, M and Bermejo-Jambrina, M and Yordanov, T and Wagener, J and Brakhage, AA and Pittl, V and Huber, LA and Haas, H and Lass-Flörl, C and Posch, W and Wilflingseder, D}, title = {β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.}, journal = {Virulence}, volume = {10}, number = {1}, pages = {957-969}, pmid = {30372658}, issn = {2150-5608}, mesh = {Aspergillosis/microbiology ; Aspergillus fumigatus/*chemistry/genetics/*immunology ; *Complement Activation ; Cytokines/immunology ; Dendritic Cells/*immunology ; Echinocandins/therapeutic use ; Humans ; Immunity, Innate ; Mutation ; Spores, Fungal/immunology ; THP-1 Cells ; *beta-Glucans ; }, abstract = {Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOn[rep] under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOn[rep] mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOn[rep] induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOn[rep]-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.}, } @article {pmid30371651, year = {2018}, author = {Drucis, K and Brzeziński, M and Gniadek, K}, title = {[Synchronous gastrointestinal stromal tumor of stomach and invasive ductal carcinoma of both breasts].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {45}, number = {268}, pages = {161-163}, pmid = {30371651}, issn = {1426-9686}, mesh = {Breast Neoplasms/*complications/diagnostic imaging/surgery ; Carcinoma, Ductal/*complications/diagnostic imaging/surgery ; Female ; Gastrointestinal Stromal Tumors/*complications/diagnostic imaging/surgery ; Humans ; Mastectomy ; Middle Aged ; Stomach/diagnostic imaging/surgery ; Stomach Neoplasms/*complications/diagnostic imaging/surgery ; }, abstract = {UNLABELLED: Gastrointestinal stromal tumor (GIST), despite the fact that it accounts for less than 5% of all sarcomas, is the most common mesenchymal tumor of the alimentary canal. Synchronous and metachronous stromal tumors are very rare findings. Only a few such cases can be found in the literature, and yet most of them is connected with Von Recklinghausen's disease or Carney's triad in which it is proved a much higher frequency of occurrence of this kind of tumors.

CASE REPORT: We present a case of 64 years old women, who was diagnosed with invasive ductal carcinoma of both breast due to screening mammography. Patent was qualified to bilateral mastectomy. Perioperative computer tomography scan revealed an additional pathological abnormality situated beyond stomach light, which after resection and immunohistochemistry was found to be a gastrointestinal stromal tumor. This case emphasize the problem of synchronous stromal tumors, the detection of which is often difficult due to nonspecific symptoms. Despite the fact that the most common localization of coexisting tumors is the digestive tract, one should remember about the possibility of occurrence in less frequent locations such as the breast.}, } @article {pmid30362671, year = {2018}, author = {Rabinovich, I and Sebastião, APM and Lima, RS and Urban, CA and Junior, ES and Anselmi, KF and Elifio-Esposito, S and De Noronha, L and Moreno-Amaral, AN}, title = {Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma.}, journal = {European journal of histochemistry : EJH}, volume = {62}, number = {3}, pages = {}, pmid = {30362671}, issn = {2038-8306}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase 1 Family ; Biomarkers, Tumor/*chemistry ; CD24 Antigen/*blood ; Carcinoma, Ductal, Breast/*classification/*diagnosis ; Female ; Humans ; Hyaluronan Receptors/*blood ; Immunohistochemistry ; Isoenzymes/*chemistry ; Lymphatic Metastasis/*pathology ; Middle Aged ; Multivariate Analysis ; Phenotype ; Prognosis ; Retinal Dehydrogenase/*chemistry ; }, abstract = {Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high histological grade and larger tumors, but it was not associated with the patients' prognosis in this sample and nor was the CD44+/CD24- phenotype in a multivariate analysis. There are still many controversies about the role of these markers in breast cancer molecular subtypes. The identification of these populations of cells, through immunohistochemical markers, can help to better understand the CSC theory in clinical practice and, in the near future, contribute to developing new target therapies.}, } @article {pmid30362328, year = {2018}, author = {Abood, RA}, title = {Breast Cancer in Basra Oncology Center: A Clinico- Epidemiological Analysis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {10}, pages = {2943-2946}, pmid = {30362328}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Iraq/epidemiology ; Male ; Middle Aged ; Neoplasm Staging/methods ; Retrospective Studies ; Young Adult ; }, abstract = {Background: Breast cancer is the most common cancer affecting women, and the leading cause of cancer-related deaths. Objective: This study was performed to evaluate clinico-epidemiological features of breast cancer from Iraq during a five-year period. Methodology: This is a retrospective descriptive study. Medical notes and histopathological reports of patients with confirmed diagnosis of breast cancer between January 2011 and December 2015 were reviewed for age, gender, site, laterality, histopathological type, grade of differentiation and TNM stage at diagnosis. Results: A total of 1,000 patients were included in the study. Mean age at diagnosis was 50 years (range 22-85 years), and females constituted 99.2% of cases. Most cases (98.7%) were unilateral and most common (85.5%) histological subtype was invasive ductal carcinoma. Majority of the cases (58%) were moderately differentiated (grade II), wherein 45% belonged to stage II in TNM system, and nearly half (49%) of patients had locally advanced or metastatic cancer. Conclusion: Breast cancer presents at least a decade earlier and at a more advanced stage in Iraqi women when compared to the Western World. Steps for early detection are essential for initiation of prompt therapy and reduction of mortality.}, } @article {pmid30359996, year = {2018}, author = {Orlandini, LF and Reis, FJCD and da Silveira, WA and Tiezzi, MG and de Andrade, JM and Ribeiro-Silva, A and Deaton, R and Bosland, M and Tiezzi, DG}, title = {Identification of a Subtype of Poorly Differentiated Invasive Ductal Carcinoma of the Breast Based on Vimentin and E-cadherin Expression.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {40}, number = {12}, pages = {779-786}, pmid = {30359996}, issn = {1806-9339}, mesh = {Breast Neoplasms/chemistry/classification/*metabolism/*pathology ; Cadherins/analysis/*biosynthesis ; Carcinoma, Ductal, Breast/chemistry/classification/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Keratin-5/analysis/*biosynthesis ; Middle Aged ; Vimentin/analysis/*biosynthesis ; }, abstract = {OBJECTIVE: The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs).

METHODS:  We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression.

RESULTS:  We have observed that luminal A and B tumors lack the VIM[+]/CDH1[-/low] phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM[+]/CDH1[-/low] phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM[+]/CDH1[-/low] tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM[+]/CDH1[-/low] tumors (23% versus 61%; X2 test; p = 0.01).

CONCLUSION:  Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.}, } @article {pmid30352176, year = {2018}, author = {Krahmer, N and Najafi, B and Schueder, F and Quagliarini, F and Steger, M and Seitz, S and Kasper, R and Salinas, F and Cox, J and Uhlenhaut, NH and Walther, TC and Jungmann, R and Zeigerer, A and Borner, GHH and Mann, M}, title = {Organellar Proteomics and Phospho-Proteomics Reveal Subcellular Reorganization in Diet-Induced Hepatic Steatosis.}, journal = {Developmental cell}, volume = {47}, number = {2}, pages = {205-221.e7}, doi = {10.1016/j.devcel.2018.09.017}, pmid = {30352176}, issn = {1878-1551}, support = {R01 GM097194/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Diet ; Diet, High-Fat ; Fatty Liver/*physiopathology ; Golgi Apparatus/physiology ; Lipid Droplets/metabolism/*physiology ; Lipid Metabolism ; Lipids/physiology ; Liver ; Mass Spectrometry/methods ; Mice ; Mice, Inbred C57BL ; Mitochondrial Membranes ; Nutrients/metabolism ; Organelles/drug effects/*physiology ; Phosphorylation ; Protein Transport ; Proteomics/methods ; Secretory Pathway ; }, abstract = {Lipid metabolism is highly compartmentalized between cellular organelles that dynamically adapt their compositions and interactions in response to metabolic challenges. Here, we investigate how diet-induced hepatic lipid accumulation, observed in non-alcoholic fatty liver disease (NAFLD), affects protein localization, organelle organization, and protein phosphorylation in vivo. We develop a mass spectrometric workflow for protein and phosphopeptide correlation profiling to monitor levels and cellular distributions of ∼6,000 liver proteins and ∼16,000 phosphopeptides during development of steatosis. Several organelle contact site proteins are targeted to lipid droplets (LDs) in steatotic liver, tethering organelles orchestrating lipid metabolism. Proteins of the secretory pathway dramatically redistribute, including the mis-localization of the COPI complex and sequestration of the Golgi apparatus at LDs. This correlates with reduced hepatic protein secretion. Our systematic in vivo analysis of subcellular rearrangements and organelle-specific phosphorylation reveals how nutrient overload leads to organellar reorganization and cellular dysfunction.}, } @article {pmid30350269, year = {2019}, author = {Jerevall, PL and Brock, J and Palazzo, J and Wieczorek, T and Misialek, M and Guidi, AJ and Wu, Y and Erlander, MG and Zhang, Y and Schnabel, CA and Goss, PE and Horick, N and Sgroi, DC}, title = {Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.}, journal = {Breast cancer research and treatment}, volume = {173}, number = {2}, pages = {375-383}, doi = {10.1007/s10549-018-5013-6}, pmid = {30350269}, issn = {1573-7217}, mesh = {Adult ; Age Factors ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/epidemiology ; Prognosis ; Prospective Studies ; Risk Assessment/methods ; Risk Factors ; Tumor Burden ; }, abstract = {PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients.

METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed.

RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk.

CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.}, } @article {pmid30341864, year = {2018}, author = {Kumar, M and Sharma, Y and Bahl, A}, title = {Evaluation of Endothelial Dysfunction in Idiopathic Dilated Cardiomyopathy Patients.}, journal = {The Journal of the Association of Physicians of India}, volume = {66}, number = {3}, pages = {26-28}, pmid = {30341864}, issn = {0004-5772}, mesh = {Blood Flow Velocity/physiology ; Cardiomyopathy, Dilated/*physiopathology ; Carotid Intima-Media Thickness ; Case-Control Studies ; Endothelium, Vascular/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Vasodilation/physiology ; }, abstract = {BACKGROUND: Endothelial dysfunction has early been characterized in ischemic cardiomyopathy patients. The study was aimed to study evaluation of endothelial dysfunction in idiopathic cardiomyopathy patients (DCM).

METHODS: Thirty newly diagnosed patients (age >18 years) of DCM were enrolled in the study from cardiology OPD, PGIMER, Chandigarh from January 2011 to June 2012. Age-and sex-matched 30 healthy controls were also enrolled. Idiopathic DCM was diagnosed by presence of left ventricular dilatation and systolic dysfunction (LVEF <40%) on echocardiography in the absence of coronary artery disease, hypertension or valvular disease. All patients underwent echocardiography and coronary arteriography. Flow mediated dilation (FMD) and carotid intima media thickness (IMT) were compared between patients and controls.

RESULTS: There was no significant difference in mean IMT between patients (0.73±0.04 mm) and controls (0.747±0.03 mm) (P=0.18). There was significant difference in left IMT in NHYA class (P=0.010). There was significant difference in mean percentage of FMD (patients vs. controls; 4.37% vs. 8.35%; P=0.001) while baseline FMD was different (patients vs. controls; 3.6 mm±0.26 mm vs. 3.72±0.32 mm; P=0.13). There was no significant difference in percentage NMD (P=0.057) and mean NMD (P=0.26) between patients and controls. There was no correlation between FMD and IMT.

CONCLUSION: Endothelial dysfunction occurs in IDC patients. Also, there is a positive correlation with NHYA class; however, IMT is not affected in dilated cardiomyopathy.}, } @article {pmid30339213, year = {2019}, author = {Jacob, T and Bracha, J}, title = {Identification of Signs and Symptoms of Axillary Web Syndrome and Breast Seroma During a Course of Physical Therapy 7 Months After Lumpectomy: A Case Report.}, journal = {Physical therapy}, volume = {99}, number = {2}, pages = {229-239}, doi = {10.1093/ptj/pzy110}, pmid = {30339213}, issn = {1538-6724}, mesh = {Aged ; Axilla/*physiopathology ; Female ; Humans ; Lymphatic Diseases/etiology/*therapy ; Lymphedema/*therapy ; Mastectomy/*adverse effects ; *Physical Therapy Modalities ; Postoperative Complications/etiology ; Seroma/etiology/*therapy ; Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: Axillary web syndrome (AWS) and seroma are common and function-limiting side effects following treatments for breast cancer. Studies of AWS and seroma are rare, and there are no guidelines for physical therapy in these cases.

CASE DESCRIPTION: After left breast lumpectomy due to invasive ductal carcinoma, a 65-year-old female patient underwent intraoperative radiation therapy and whole breast radiation. Seven months later, during treatment for breast swelling, AWS and breast seroma were identified by a physical therapist certified in lymphedema treatment. Treatment goals were to reduce breast swelling and pain and to improve shoulder movements. Interventions included manual lymph drainage, left arm stretching, and instruction about self-lymphatic-drainage and stretching exercise. Also, a compression bra was ordered, and continued daily activities and physical activity were recommended.

OUTCOMES: Improvement in shoulder movement, breast swelling, and pain.

DISCUSSION: Because evidence for treatment guidelines following treatments for breast cancer is lacking, close follow-up for treatment-related complications is recommended. Management should be chosen according to signs and symptoms. Realistic expectations can reduce patient frustration and improve coping strategies and compliance with self-treatment demands. Clinical studies to support these conclusions are required.}, } @article {pmid30332671, year = {2019}, author = {Kitamura, M and Nakayama, T and Mukaisho, KI and Mori, T and Umeda, T and Moritani, S and Kushima, R and Tani, M and Sugihara, H}, title = {Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {86}, number = {2-3}, pages = {92-101}, doi = {10.1159/000492833}, pmid = {30332671}, issn = {1423-0291}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; *Disease Progression ; Female ; GATA3 Transcription Factor/genetics ; Humans ; Middle Aged ; Paraffin Embedding ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors.

METHODS: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering.

RESULTS: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters.

CONCLUSION: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.}, } @article {pmid30325954, year = {2018}, author = {Dhage, S and Ernlund, A and Ruggles, K and Axelrod, D and Berman, R and Roses, D and Schneider, RJ}, title = {A genomic ruler to assess oncogenic transition between breast tumor and stroma.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205602}, pmid = {30325954}, issn = {1932-6203}, support = {T32 CA009161/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/surgery ; Cell Transformation, Neoplastic/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genomics ; Humans ; Mastectomy ; Microarray Analysis ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; RNA, Messenger/metabolism ; Stromal Cells/*metabolism/pathology ; }, abstract = {BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation.

METHODS AND FINDINGS: Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways.

CONCLUSIONS: The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.}, } @article {pmid30320622, year = {2018}, author = {Martin-Rosello, ML and Sanz-Amores, MR and Salvador-Comino, MR}, title = {Instruments to evaluate complexity in end-of-life care.}, journal = {Current opinion in supportive and palliative care}, volume = {12}, number = {4}, pages = {480-488}, doi = {10.1097/SPC.0000000000000403}, pmid = {30320622}, issn = {1751-4266}, mesh = {Communication ; Comorbidity ; Cooperative Behavior ; Humans ; Palliative Care/*organization & administration ; Patient Care Team/organization & administration ; Patient-Centered Care/organization & administration ; Primary Health Care/organization & administration ; Quality of Health Care/*organization & administration ; Socioeconomic Factors ; *Systems Analysis ; Terminal Care/*organization & administration ; }, abstract = {PURPOSE OF REVIEW: The growing number of patients with terminal and chronic conditions and co-morbidities constitutes a challenge for any healthcare system, to provide effective and efficient patient-centred care at the end of life. Resources are limited, and complexity is rising within patients' situations and healthcare professionals interventions. This review presents the state of art of the role of complexity in specialist palliative care provision.

RECENT FINDINGS: Although studies related to complexity in palliative care are still limited, interesting reviews on complexity frameworks in co-morbidity conditions and palliative care are growing more present in current literature. They identify multidimensional issues, resource utilisation, and the relationship between them as fundamental aspects of complexity constructs, helping to define and understand complexity, and to therefore design validated tools to support healthcare professionals identifying the most complex patients, such as Hui's criteria, PALCOM, INTERMED, and IDC-Pal which is presented in this review.

SUMMARY: There is an urgent need to guarantee quality and equity of care for all the patients eligible for palliative care, from those who need a palliative care approach to those needing specialist intensive palliative care. Implementing complexity theory into practice is paramount. In this review, complexity science, complexity frameworks, as well as tools evaluating complexity in palliative care are described.}, } @article {pmid30319932, year = {2018}, author = {Srinivasan, SM and Cavagnino, DT and Bhat, AN}, title = {Effects of Equine Therapy on Individuals with Autism Spectrum Disorder: A Systematic Review.}, journal = {Review journal of autism and developmental disorders}, volume = {5}, number = {2}, pages = {156-175}, pmid = {30319932}, issn = {2195-7185}, support = {S10 OD021534/OD/NIH HHS/United States ; R03 HD060809/HD/NICHD NIH HHS/United States ; R21 MH089441/MH/NIMH NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; R33 MH089441/MH/NIMH NIH HHS/United States ; }, abstract = {Literature on effects of equine therapy in individuals with autism spectrum disorder (ASD) has grown in recent times. Equine therapy is an alternative multimodal intervention that involves utilizing a horse to enhance core impairments in ASD. Recent systematic reviews in this area have several limitations including inclusion of populations other than ASD, assessment of a variety of animal-assisted interventions other than equine therapy, and a failure to conduct quantitative analyses to provide accurate effect size estimates. We conducted a focused systematic review to address these limitations. Our review suggested that equine therapy has beneficial effects on behavioral skills and to some extent on social communication in ASD. The evidence for positive effects of equine therapy on perceptuo-motor, cognitive, and functional skills is currently limited.}, } @article {pmid30317746, year = {2018}, author = {Yuan, P and Ying, JM}, title = {[Advances on the molecular characteristics of breast invasive ductal carcinoma and invasive lobular carcinoma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {47}, number = {10}, pages = {808-811}, doi = {10.3760/cma.j.issn.0529-5807.2018.10.021}, pmid = {30317746}, issn = {0529-5807}, } @article {pmid30310523, year = {2018}, author = {Kono, M and Fujii, T and Matsuda, N and Harano, K and Chen, H and Wathoo, C and Joon, AY and Tripathy, D and Meric-Bernstam, F and Ueno, NT}, title = {Somatic mutations, clinicopathologic characteristics, and survival in patients with untreated breast cancer with bone-only and non-bone sites of first metastasis.}, journal = {Journal of Cancer}, volume = {9}, number = {19}, pages = {3640-3646}, pmid = {30310523}, issn = {1837-9664}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; UL1 TR000371/TR/NCATS NIH HHS/United States ; }, abstract = {Background: Bone is the most common site of metastasis of breast cancer. Biological mechanisms of metastasis to bone may be different from mechanisms of metastasis to non-bone sites, and identification of distinct signaling pathways and somatic mutations may provide insights on biology and rational targets for treatment and prevention of bone metastasis. The aims of this study were to compare and contrast somatic mutations, clinicopathologic characteristics, and survival in breast cancer patients with bone-only versus non-bone sites of first metastasis. Methods: Primary tumor samples were collected before treatment from 389 patients with untreated primary breast cancer and distant metastasis at diagnosis. In each sample, 46 or 50 cancer-related genes were analyzed for mutations by AmpliSeq Ion Torrent next-generation sequencing. Fisher's exact test was used to identify somatic mutations associated with bone-only first metastasis. Logistic regression models were used to identify differences in detected somatic mutations, clinicopathologic characteristics, and survival between patients with bone-only first metastasis and patients with first metastasis in non-bone sites only ("other-only first metastasis"). Results: Among the 389 patients, 72 (18.5%) had bone-only first metastasis, 223 (57.3%) had other-only first metastasis, and 94 (24.2%) had first metastasis in both bone and non-bone sites. The most commonly mutated genes were TP53 (N=103), PIK3CA (N=79), AKT (N=13), and PTEN (N=2). Compared to patients with other-only first metastasis, patients with bone-only first metastasis had higher rates of hormone-receptor-positive disease, non-triple-negative subtype, and lower grade (grade 1 or 2; Nottingham grading system) (all three comparisons, p<0.001); had a lower ratio of cases of invasive ductal carcinoma to cases of invasive lobular carcinoma (p=0.002); and tended to have a higher 5-year overall survival (OS) rate (78.2% [95% confidence interval (CI), 68.6%-89.0%] vs 55.0% [95% CI, 48.1%-62.9%]; p=0.051). However, in the subgroup of patients with TP53 mutation and in the subgroup of patients with PIK3CA mutation, OS did not differ between patients with bone-only and other-only first metastasis (p=0.49 and p=0.68, respectively). In univariate analysis, the rate of TP53 mutation tended to be lower in patients with bone-only first metastasis than in those with other-only first metastasis (15.3% vs 29.1%; p=0.051). In multivariate analysis, TP53 mutation was not significantly associated with site of first metastasis (p=0.54) but was significantly associated with hormone-receptor-negative disease (p<0.001). Conclusions: We did not find associations between somatic mutations and bone-only first metastasis in patients with untreated breast cancer. Patients with bone-only first metastasis tend to have longer OS than patients with other-only first metastasis. More comprehensive molecular analysis may be needed to further understand the factors associated with bone-only metastatic disease in breast cancer.}, } @article {pmid30306389, year = {2018}, author = {DeVaux, RS and Herschkowitz, JI}, title = {Beyond DNA: the Role of Epigenetics in the Premalignant Progression of Breast Cancer.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {23}, number = {4}, pages = {223-235}, pmid = {30306389}, issn = {1573-7039}, mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA/*genetics ; Disease Progression ; Epigenesis, Genetic/*genetics ; Female ; Humans ; }, abstract = {Ductal Carcinoma in Situ (DCIS) is an early breast cancer lesion that is considered a nonobligate precursor to development of invasive ductal carcinoma (IDC). Although only a small subset of DCIS lesions are predicted to progress into a breast cancer, distinguishing innocuous from minacious DCIS lesions remains a clinical challenge. Thus, patients diagnosed with DCIS will undergo surgery with the potential for radiation and hormone therapy. This has led to a current state of overdiagnosis and overtreatment. Interrogating the transcriptome alone has yet to define clear functional determinants of progression from DCIS to IDC. Epigenetic changes, critical for imprinting and tissue specific development, in the incorrect context can lead to global signaling rewiring driving pathological phenotypes. Epigenetic signaling pathways, and the molecular players that interpret and sustain their signals, are critical to understanding the underlying pathology of breast cancer progression. The types of epigenetic changes, as well as the molecular players, are expanding. In addition to DNA methylation, histone modifications, and chromatin remodeling, we must also consider enhancers as well as the growing field of noncoding RNAs. Herein we will review the epigenetic interactions that have been uncovered in early stage lesions that impact breast cancer progression, and how these players may be utilized as biomarkers to mitigate overdiagnosis and overtreatment.}, } @article {pmid30305801, year = {2018}, author = {Hashmi, AA and Naz, S and Hashmi, SK and Hussain, ZF and Irfan, M and Khan, EY and Faridi, N and Khan, A and Edhi, MM}, title = {Prognostic significance of p16 & p53 immunohistochemical expression in triple negative breast cancer.}, journal = {BMC clinical pathology}, volume = {18}, number = {}, pages = {9}, pmid = {30305801}, issn = {1472-6890}, abstract = {BACKGROUND: p16 and p53 genes are frequently mutated in triple negative breast cancer & prognostic value of these mutations have been shown; however, their role as immunohistochemical overexpression has not been fully validated. Therefore we aimed to evaluate the association of p16 and p53 overexpression in triple negative breast cancer with various prognostic parameters.

METHODS: Total 150 cases of triple negative breast cancers were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. ER, PR and Her2neu immunohistochemistry were re-performed to confirm triple negative status. p16 & p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined.

RESULTS: Mean age of the patients involved in the study was 48.9 years. Most of the patients presented at stage T2 with a high mean ki67 index i.e. 46.9%. 42.7% of cases had nodal metastasis. Although 84% cases were of invasive ductal carcinoma; however a significant proportion of cases were of metaplastic histology (9.3%). Fifty-one percent (76 cases) of cases showed positive p53 expression while 49% (74 cases) were negative. Higher percentage of p53 expression was found to correlate with higher T stage, high ki67 index and higher nodal stage. On the other hand, strong intensity of p53 expression was positively correlated with higher tumor grade and ki67 index. Seventy-one percent (98 cases) of cases showed positive p16 expression, whereas 24.8% (34 cases) were negative and 3.6% (5 cases) showed focal positive p16 expression. However, no significant association was found between p16 expression and various clinical and pathologic parameters. Similarly, no significant association of either p16 or p53 over-expression was noted with recurrence status of patients.

CONCLUSION: On the basis of significant association of p53 over-expression with worse prognostic factors in triple negative breast cancer, therefore we suggest that more large scale studies are needed to validate this finding in loco-regional population. Moreover, high expression of p16 in triple negative breast cancer suggests a potential role of this biomarker in triple negative breast cancer pathogenesis which should be investigated with molecular based research in our population.}, } @article {pmid30305012, year = {2018}, author = {Vitkin, E and Solomon, O and Sultan, S and Yakhini, Z}, title = {Genome-wide analysis of fitness data and its application to improve metabolic models.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {368}, pmid = {30305012}, issn = {1471-2105}, mesh = {Exercise Test/*methods ; Genome-Wide Association Study/*methods ; Genomics/*methods ; Humans ; Models, Biological ; }, abstract = {BACKGROUND: Synthetic biology and related techniques enable genome scale high-throughput investigation of the effect on organism fitness of different gene knock-downs/outs and of other modifications of genomic sequence.

RESULTS: We develop statistical and computational pipelines and frameworks for analyzing high throughput fitness data over a genome scale set of sequence variants. Analyzing data from a high-throughput knock-down/knock-out bacterial study, we investigate differences and determinants of the effect on fitness in different conditions. Comparing fitness vectors of genes, across tens of conditions, we observe that fitness consequences strongly depend on genomic location and more weakly depend on gene sequence similarity and on functional relationships. In analyzing promoter sequences, we identified motifs associated with conditions studied in bacterial media such as Casaminos, D-glucose, Sucrose, and other sugars and amino-acid sources. We also use fitness data to infer genes associated with orphan metabolic reactions in the iJO1366 E. coli metabolic model. To do this, we developed a new computational method that integrates gene fitness and gene expression profiles within a given reaction network neighborhood to associate this reaction with a set of genes that potentially encode the catalyzing proteins. We then apply this approach to predict candidate genes for 107 orphan reactions in iJO1366. Furthermore - we validate our methodology with known reactions using a leave-one-out approach. Specifically, using top-20 candidates selected based on combined fitness and expression datasets, we correctly reconstruct 39.7% of the reactions, as compared to 33% based on fitness and to 26% based on expression separately, and to 4.02% as a random baseline. Our model improvement results include a novel association of a gene to an orphan cytosine nucleosidation reaction.

CONCLUSION: Our pipeline for metabolic modeling shows a clear benefit of using fitness data for predicting genes of orphan reactions. Along with the analysis pipelines we developed, it can be used to analyze similar high-throughput data.}, } @article {pmid30303137, year = {2018}, author = {Jafarian, AH and Tasbandi, A and Gilan, H and Sheikhi, M and Roshan, NM}, title = {Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.}, journal = {Indian journal of pathology & microbiology}, volume = {61}, number = {4}, pages = {500-504}, doi = {10.4103/IJPM.IJPM_67_18}, pmid = {30303137}, issn = {0974-5130}, mesh = {Adult ; Aged ; CD4 Antigens/*analysis ; CD8 Antigens/*analysis ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Cross-Sectional Studies ; Female ; Humans ; Immunohistochemistry ; Ki-1 Antigen/*analysis ; Middle Aged ; Prognosis ; Triple Negative Breast Neoplasms/*immunology/mortality/pathology ; }, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors.

MATERIALS AND METHODS: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels.

RESULTS: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes.

CONCLUSION: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.}, } @article {pmid30300673, year = {2018}, author = {Golland, Y and Hakim, A and Aloni, T and Schaefer, S and Levit-Binnun, N}, title = {Affect dynamics of facial EMG during continuous emotional experiences.}, journal = {Biological psychology}, volume = {139}, number = {}, pages = {47-58}, doi = {10.1016/j.biopsycho.2018.10.003}, pmid = {30300673}, issn = {1873-6246}, mesh = {Adult ; Electromyography ; Emotions/*physiology ; *Facial Expression ; Facial Muscles/*physiology ; Female ; Humans ; Male ; Time Factors ; Young Adult ; }, abstract = {Emotional experiences are complex, multi-component processes that unfold over time. Accordingly, it is crucial to understand the temporal dynamics of these constituent components. Here we studied the dynamics of one of the core emotional systems, i.e. facial muscle activity, during continuous emotional experiences, elicited by movies. We found that transient zygomatic fluctuations were narrowly tuned to a positive emotional experience. During a positive but not a negative movie, zygomatic response patterns were consistent across participants, tracked with subjective ratings and co-varied with emotional dynamics. Corrugator activity evidenced a broader affective profile and larger individual variability. It was coordinated with tonic changes in emotional negativity and inversely coupled with transient changes in positive affect. Taken together, our results confirmed previous findings on the affective profiles of facial responses and extended them to temporal dynamics. They further uncovered important differences in temporal response characteristics of zygomatic and corrugator measures.}, } @article {pmid30295149, year = {2019}, author = {Yemul, KS and Zysk, AM and Richardson, AL and Tangella, KV and Jacobs, LK}, title = {Interpretation of Optical Coherence Tomography Images for Breast Tissue Assessment.}, journal = {Surgical innovation}, volume = {26}, number = {1}, pages = {50-56}, doi = {10.1177/1553350618803245}, pmid = {30295149}, issn = {1553-3514}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Case-Control Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Reference Values ; Tissue Embedding ; Tomography, Optical Coherence/*methods ; }, abstract = {PURPOSE: Initial studies have shown that optical coherence tomography (OCT) is an effective margin-evaluation tool for breast-conserving surgery, but methods for the interpretation of breast OCT images have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe. OCT images and corresponding histology were used to develop guidelines for the identification of breast tissue features in OCT images.

METHODS: Mastectomy and breast-conserving surgery specimens from 26 women were imaged with a handheld OCT probe. During standard pathology specimen dissection, representative 1-cm × 1-cm tissue regions were grossly identified, assessed with OCT, inked for orientation and image-matching purposes, and processed. Histology slides corresponding to the OCT image region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches.

RESULTS: In total, 2880 OCT images were acquired from 26 breast specimens (from 26 patients) and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, cyst, fibroadenoma, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns.

CONCLUSIONS: This is the first work to systematically catalog the critical features of breast OCT images. The results indicate that OCT can be used to identify and distinguish between benign and malignant features in human breast tissue.}, } @article {pmid30293819, year = {2019}, author = {Roknsharifi, S and Fishman, MDC and Agarwal, MD and Brook, A and Kharbanda, V and Dialani, V}, title = {The role of diffusion weighted imaging as supplement to dynamic contrast enhanced breast MRI: Can it help predict malignancy, histologic grade and recurrence?.}, journal = {Academic radiology}, volume = {26}, number = {7}, pages = {923-929}, doi = {10.1016/j.acra.2018.09.003}, pmid = {30293819}, issn = {1878-4046}, mesh = {Adenocarcinoma, Mucinous/*diagnostic imaging/pathology ; Adult ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnostic imaging ; Neoplasms, Complex and Mixed/*diagnostic imaging/pathology ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {RATIONALE AND OBJECTIVES: To evaluate the value of adding Diffusion Weighted Imaging (DWI) with Apparent Diffusion Coefficient (ADC) mapping to dynamic contrast enhanced (DCE-MRI) to distinguish benign from malignant pathology subtypes and tumor recurrence.

METHOD AND MATERIALS: In this retrospective IRB approved study, 956 consecutive patients underwent bilateral breast MRI between 1/2015 and 12/2015, with 156 BIRADS 4, 5, or 6 lesions detected in 111 patients. DWI imaging at B0, B100, B600, B1000 was performed with DCE-MRI. Values for diffusion and ADC images were recorded by two fellowship-trained breast radiologists. Mean ADC and signal intensity (SI) values were correlated with histology, tumor grade, hormone receptors (ER, PR, and HER-2)and Oncotype DX scores, when available. p ≤ 0.05 was considered significant.

RESULTS: Of 156 lesions, there were 59 (38%) benign lesions, 24 (15%) Ductal Carcinoma In-Situ, 47 (30%) Invasive Ductal Carcinoma (IDC), 15 (10%) Invasive Lobular Carcinoma (ILC) and 2 (2%) Mucinous carcinoma (MC), five (5%) mixed IDC and ILC, and four (4%) other, including tubular and rare types of malignancy. Mean ADC values for malignancy were significantly lower than for benign lesions (1085 ± 343 × 10[-][6] vs 1481 ± 276 × 10[-][6] mm[2]/s), which is highly predictive (area under curve = 0.82). In addition, tumors with PR negativity and Oncotype score ≥18 (intermediate to high risk for recurrence) demonstrated significantly lower ADC values. SI at B100 and B600 was helpful in distinguishing benign versus IDC. There was no significant correlation between ADC values and tumor grade or ER/HER2 status.

CONCLUSION: ADC value is important factor in distinguishing malignancy, differentiating tumors with higher Oncotype score, and PR negativity. Therefore, it can be used as an important tool to assist appropriate treatment selection.}, } @article {pmid30290054, year = {2018}, author = {Gaowa, S and Futamura, M and Tsuneki, M and Kamino, H and Tajima, JY and Mori, R and Arakawa, H and Yoshida, K}, title = {Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.}, journal = {Cancer science}, volume = {109}, number = {12}, pages = {3910-3920}, pmid = {30290054}, issn = {1349-7006}, support = {15ck0106006 h0002 (to HA)//AMED/ ; H26-practical-general-001 (to HA)//Ministry of Health, Labour and Welfare for the Practical Research for Innovative Cancer/ ; 23659178 (to HA)//KAKENIHI/ ; 24240117 (to HA)//KAKENIHI/ ; 17K10542 (to MF)//KAKENIHI/ ; 25670169 (to HA)//KAKENIHI/ ; 29-E-1 (to HA), 30-A-3 (to HA)//The National Cancer Center Research and Development Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Caspases/metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; DNA Methylation ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Mitochondria/metabolism ; Mitochondrial Proteins/*genetics/*metabolism ; Mutation ; Promoter Regions, Genetic ; Tumor Suppressor Protein p53/*genetics/*metabolism ; }, abstract = {Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.}, } @article {pmid30288049, year = {2018}, author = {Shi, F and Chang, H and Zhou, Q and Zhao, YJ and Wu, GJ and Song, QK}, title = {Distribution of CD4[+] and CD8[+] exhausted tumor-infiltrating lymphocytes in molecular subtypes of Chinese breast cancer patients.}, journal = {OncoTargets and therapy}, volume = {11}, number = {}, pages = {6139-6145}, pmid = {30288049}, issn = {1178-6930}, abstract = {PURPOSE: Breast cancer (BC) is the leading cancer affecting Chinese women; however, the immune microenvironment between molecular subtypes is less reported. This study aimed to investigate the distribution of tumor-infiltrating lymphocyte (TIL) subpopulations, especially exhausted CD4[+] and CD8[+] TILs in Chinese BC patients.

PATIENTS AND METHODS: A total of 133 patients with breast invasive ductal carcinoma were recruited consecutively from January 1, 2012 to December 31, 2013, and TILs were detected in H&E-stained sections. Expression profiling of PD-1, CD4, and CD8 was determined by immunohistochemistry on 4 µm formalin-fixed paraffin-embedded tissue sections. The distribution of TILs was analyzed based on hormone receptor status and molecular subtypes.

RESULTS: PD-1[+], CD4[+], and CD8[+] TILs distributed differently based on molecular subtypes. Compared to Luminal A, triple-negative breast cancer (TNBC) patients had more PD-1[+] TILs (39/high-power field [HPF] vs 11/HPF), PD-1[+] helper T (CD4[+]) cells (28/HPF vs 10/HPF), and PD-1[+] cytotoxic (CD8[+]) T-cells (3/HPF vs 2/HPF).

CONCLUSION: TILs are distributed differently based on molecular subtypes. TNBC patients exhibit more PD-1[+] exhausted TILs, representing an inhibitory immune microenvironment. PD-1/PD-L1 pathway is a potential therapeutic target of TNBC.}, } @article {pmid30287681, year = {2018}, author = {Ng, CS and Sinha, A and Aniweh, Y and Nah, Q and Babu, IR and Gu, C and Chionh, YH and Dedon, PC and Preiser, PR}, title = {tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum.}, journal = {Molecular systems biology}, volume = {14}, number = {10}, pages = {e8009}, pmid = {30287681}, issn = {1744-4292}, mesh = {Codon ; Epigenesis, Genetic ; Erythrocytes ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Humans ; Plasmodium falciparum/genetics/*physiology ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Proteomics/methods ; Protozoan Proteins/*genetics/*metabolism ; RNA, Transfer/*metabolism ; }, abstract = {Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra-erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up-regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up- and down-regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage-specific proteins by enhancing translation efficiency of codon-biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.}, } @article {pmid30287091, year = {2018}, author = {Schumacher, D and Morgenstern, J and Oguchi, Y and Volk, N and Kopf, S and Groener, JB and Nawroth, PP and Fleming, T and Freichel, M}, title = {Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes.}, journal = {Molecular metabolism}, volume = {18}, number = {}, pages = {143-152}, pmid = {30287091}, issn = {2212-8778}, mesh = {Aged ; Aldo-Keto Reductases/metabolism ; Animals ; Diabetes Mellitus, Experimental/*metabolism ; Diabetes Mellitus, Type 2/*metabolism ; Female ; Glycation End Products, Advanced/metabolism ; Humans ; Kidney/metabolism ; Lactoylglutathione Lyase/genetics/metabolism ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Pyruvaldehyde/*metabolism ; }, abstract = {OBJECTIVES: The deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.

METHODS: CRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1[-/-]) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.

RESULTS: Glo1[-/-] mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1[-/-] mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.

CONCLUSIONS: These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.}, } @article {pmid30284978, year = {2018}, author = {Liu, YJ and Cheng, D and Li, YX and Zhang, JD and Yang, HX}, title = {A new one-dimensional Cd[II] coordination polymer incorporating 2,2'-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylate).}, journal = {Acta crystallographica. Section C, Structural chemistry}, volume = {74}, number = {Pt 10}, pages = {1128-1132}, doi = {10.1107/S2053229618012603}, pmid = {30284978}, issn = {2053-2296}, support = {16 A350002//Program for the Key Scientific Research Project of Colleges and Universities in Henan Province/International ; 152300410214//Henan Province Basic and Frontier Technology Research Projects/International ; }, abstract = {Imidazole-4,5-dicarboxylic acid (H3IDC) and its derivatives are widely used in the preparation of new coordination polymers owing to their versatile bridging coordination modes and potential hydrogen-bonding donors and acceptors. A new one-dimensional coordination polymer, namely catena-poly[[diaquacadmium(II)]-μ3-2,2'-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylato)], [Cd(C16H6N4O8)0.5(H2O)2]n or [Cd(H2Phbidc)1/2(H2O)2]n, has been synthesized by the reaction of Cd(OAc)2·2H2O (OAc is acetate) with 2,2'-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylic acid) (H6Phbidc) under solvothermal conditions. In the polymer, one type of Cd ion (Cd1) is six-coordinated by two N atoms and two O atoms from one H2Phbidc[4-] ligand and by two O atoms from two water molecules, forming a significantly distorted octahedral CdN2O4 coordination geometry. In contrast, the other type of Cd ion (Cd2) is six-coordinated by two N atoms and two O atoms from two symmetry-related H2Phbidc[4-] ligands and by two O atoms from two symmetry-related water molecules, leading to a more regular octahedral coordination geometry. The Cd1 and Cd2 ions are linked by H2Phbidc[4-] ligands into a one-dimensional chain which runs parallel to the b axis. In the crystal, the one-dimensional chains are connected through hydrogen bonds, generating a two-dimensional layered structure parallel to the ab plane. Adjacent layers are further linked by hydrogen bonds, forming a three-dimensional structure in the solid state.}, } @article {pmid30283064, year = {2018}, author = {Leontiev, A and Reuveni, Y}, title = {Augmenting GPS IWV estimations using spatio-temporal cloud distribution extracted from satellite data.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14785}, pmid = {30283064}, issn = {2045-2322}, abstract = {Water vapor (WV) is the most variable greenhouse gas in the troposphere, therefore investigation of its spatio-temporal distribution and motion is of great importance in meteorology and climatology studies. Here, we suggest a new strategy for augmenting integrated water vapor (IWV) estimations using both remote sensing satellites and global positioning system (GPS) tropospheric path delays. The strategy is based first on the ability to estimate METEOSAT-10 7.3 µm WV pixel values by extracting the mathematical dependency between the IWV amount calculated from GPS zenith wet delays (ZWD) and the METEOSAT-10 data. We then use the surface temperature differences between ground station measurements and METEOSAT-10 10.8 µm infra-red (IR) channel to identify spatio-temporal cloud distribution structures. As a last stage, the identified cloud features are mapped into the GPS-IWV distribution map when preforming the interpolation between adjusted GPS station inside the network. The suggested approach improves the accuracy of estimated regional IWV maps, in comparison with radiosonde data, thus enables to obtain the total water amount at the atmosphere, both in the form of clouds and vapor. Mean and root mean square (RMS) difference between the GPS-IWV estimations, using the spatio-temporal clouds distribution, and radiosonde data are reduced from 1.77 and 2.81 kg/m[2] to 0.74 and 2.04 kg/m[2], respectively. Furthermore, by improving the accuracy of the estimated regional IWV maps distribution it is possible to increase the accuracy of regional Numerical Weather Prediction (NWP) platforms.}, } @article {pmid30282082, year = {2019}, author = {Roininen, N and Takala, S and Haapasaari, KM and Jukkola-Vuorinen, A and Mattson, J and Heikkilä, P and Karihtala, P}, title = {Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A.}, journal = {Oncology}, volume = {96}, number = {3}, pages = {147-155}, doi = {10.1159/000493348}, pmid = {30282082}, issn = {1423-0232}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Neuroendocrine/*metabolism/pathology ; Cyclin-Dependent Kinase Inhibitor p27/*biosynthesis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Intestinal Neoplasms/*metabolism/pathology ; Middle Aged ; Neuroendocrine Tumors/*metabolism/pathology ; Pancreatic Neoplasms/*metabolism/pathology ; Proto-Oncogene Proteins/*biosynthesis ; Receptors, Somatostatin/*biosynthesis ; Retrospective Studies ; Stomach Neoplasms/*metabolism/pathology ; Thymidylate Synthase/biosynthesis ; }, abstract = {OBJECTIVES: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC.

METHODS: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC).

RESULTS: Nuclear and cytoplasmic TS, nuclear and cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was associated with excellent distant disease-free survival (p = 0.013), cytoplasmic menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27 with longer breast cancer-specific survival (p = 0.022).

CONCLUSIONS: There is a striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and NEBC also appear to show similar expression patterns of the studied markers, while there are notable differences compared to IDC. Due to the wide expression of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be evaluated.}, } @article {pmid30277674, year = {2018}, author = {Thiel, F and Ein-Dor, T and Dishy, G and King, A and Dekel, S}, title = {Examining Symptom Clusters of Childbirth-Related Posttraumatic Stress Disorder.}, journal = {The primary care companion for CNS disorders}, volume = {20}, number = {5}, pages = {}, doi = {10.4088/PCC.18m02322}, pmid = {30277674}, issn = {2155-7780}, mesh = {Adult ; Cluster Analysis ; Female ; Humans ; Labor, Obstetric/*psychology ; North America/epidemiology ; Pregnancy ; Puerperal Disorders/epidemiology/*psychology ; Stress Disorders, Post-Traumatic/epidemiology/*psychology ; Term Birth/*psychology ; Young Adult ; }, abstract = {OBJECTIVE: Recent studies document posttraumatic stress disorder (PTSD) symptoms in women following at-term deliveries with health baby outcomes. However, the notion that childbirth can trigger PTSD remains controversial, and the symptom clusters are mostly unknown. The objective of this study was to examine the clustering of childbirth-induced postpartum PTSD (PP-PTSD) symptoms in comparison to DSM-5 clusters.

METHODS: We examined the symptom presentation of childbirth-related postpartum PTSD (PP-PTSD) in a sample of 685 women. The majority of these women delivered at term. Peritraumatic stress reactions to childbirth and PP-PTSD symptoms were assessed approximately 3 months after delivery. A hierarchical cluster analysis was used to detect grouping of the PP-PTSD symptoms.

RESULTS: Childbirth-related peritraumatic stress was strongly and positively associated with PP-PTSD symptom severity. Cluster modeling revealed 4 distinguished symptom groups: reliving (some reexperiencing symptoms), namely nightmares and flashbacks; avoidance coupled with unwanted memories (other reexperiencing symptoms); negative cognitions and mood; and hyperarousal reactivity.

CONCLUSIONS: Our findings show that the representation of symptoms of PTSD that develops following a stressogenic childbirth experience appears, for the most part, to resemble DSM-5 symptom clusters. More research integrating descriptive symptom assessment with biological measures is warranted to better characterize the symptom presentation of this neglected posttraumatic stress syndrome.}, } @article {pmid30276443, year = {2019}, author = {Fortis, SP and Vaxevanis, CK and Mahaira, LG and Sofopoulos, M and Sotiriadou, NN and Dinou, A and Arnogiannaki, N and Stavropoulos-Giokas, C and Thanos, D and Baxevanis, CN and Perez, SA}, title = {Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {68}, number = {1}, pages = {57-70}, doi = {10.1007/s00262-018-2252-7}, pmid = {30276443}, issn = {1432-0851}, support = {Grant GER_1968 (ISPEBREAST)//GSTR/ ; Donation//Haegeman-Goossens family/ ; }, mesh = {Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/classification/*genetics/immunology ; Cytokines/blood ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Leukocytes, Mononuclear/metabolism ; MicroRNAs/blood/*genetics ; Prognosis ; }, abstract = {Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three "signatures" needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.}, } @article {pmid30273605, year = {2019}, author = {Hannafon, BN and Ding, WQ}, title = {Functional Role of miRNAs in the Progression of Breast Ductal Carcinoma in Situ.}, journal = {The American journal of pathology}, volume = {189}, number = {5}, pages = {966-974}, pmid = {30273605}, issn = {1525-2191}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Disease Progression ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS.}, } @article {pmid30271480, year = {2018}, author = {Wang, W and Chen, X and Lin, L and Fei, X and Garfield, DH and Hong, J and Gao, W and Zhu, S and Wu, J and Huang, O and He, J and Li, Y and Zhu, L and Chen, W and Shen, K}, title = {Distribution and Clinical Utility of the 21-gene Recurrence Score in Pure Mucinous Breast Cancer Patients: a case-control study.}, journal = {Journal of Cancer}, volume = {9}, number = {18}, pages = {3216-3224}, pmid = {30271480}, issn = {1837-9664}, abstract = {The 21-gene recurrence score (RS) is increasingly being used for patients with early stage, hormone receptor-positive, Her-2-negative breast cancer. However, these results are largely from populations with infiltrating ductal carcinoma (IDC). The clinical value of RS testing in mucinous carcinoma has not been well investigated. Pure mucinous breast cancer (PMBC) and paired pure IDC patients who underwent 21-gene RS were retrospectively reviewed and matched with tumor stage and molecular subtype. Clinic-pathological factors, treatment strategies, and RS distribution were compared between the PMBC and IDC patients. A total of 35 PMBC and 70 IDC patients were included. We found that RS was lower in the PMBC as compared with the IDC group: 21.26 vs. 24.40 (P=0.037). Regarding RS categories, PMBC patients had a relatively lower percentage of high RS patients than the IDC group: 8.57% vs. 22.86% (P = 0.048). Multivariate analysis showed that histologic type was an independent factor predicting RS distribution: IDC patients were associated with a higher RS as compared with PMBC patients (OR: 1.27, 95% CI: 1.03-2.13; P=0.014). Among genes in 21-gene RS testing, HER2, STMY3, STK15, and BAG1 were significantly different between the PMBC and IDC groups (P < 0.05). Two patients (5.71%) in the PMBC group, both with high RS, were recommended to receive adjuvant chemotherapy, much lower than patients with IDC (57.14%, P < 0.001). In multivariate analysis, histologic type of IDC was an independent factor for chemotherapy recommendation (OR = 22.00, 95% CI: 4.89-98.97, P<0.001). With a medium follow-up time of 24 months, one IDC patient had ipsilateral axillary lymph nodes recurrence and one PMBC patient had contralateral breast cancer. In conclusion, PMBC patients, mostly classified with low or intermediate RS category, were associated with lower RS as compared with IDC patients. PMBC and IDC had different genes expression patterns. Patients with high RS in the PMBC group might be recommended to receive adjuvant chemotherapy, which deserves further clinical evaluation.}, } @article {pmid30261528, year = {2018}, author = {Kopf, S and Nawroth, PP}, title = {Diabetic Pulmopathy: A New Clinical Challenge for Diabetology.}, journal = {Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {126}, number = {9}, pages = {590-591}, doi = {10.1055/a-0715-2743}, pmid = {30261528}, issn = {1439-3646}, mesh = {*Diabetes Complications/therapy ; Diabetes Mellitus, Type 2/*complications ; Exercise Therapy ; Humans ; Pulmonary Fibrosis/diagnosis/*etiology/therapy ; }, } @article {pmid30259349, year = {2018}, author = {Fabbri, M and Vitale, C and Cuoco, S and Beracci, A and Calabrese, R and Cordella, M and Mazzotta, R and Barone, P and Pellecchia, MT and Santangelo, G}, title = {Theory of mind and joint action in Parkinson's disease.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {18}, number = {6}, pages = {1320-1337}, pmid = {30259349}, issn = {1531-135X}, mesh = {Affect/physiology ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*psychology ; *Social Perception ; Theory of Mind/*physiology ; }, abstract = {It has been suggested that the Theory of Mind (ToM) may rely on more basic processes of social cognition, such as action control (e.g., joint action), even if little is known about this relationship. The relationship between ToM and joint action can be studied in patients with Parkinson's disease (PD), because they are characterized not only by a deficit in ToM (and in its cognitive and affective subcomponents) but also by a deficit in the inhibition of competing responses. Sixty PD patients and 60 matched healthy controls (HCs) performed a go/no-go Flanker task in both joint and individual conditions. Cognitive (Advanced Test or AT) and affective (Emotion Attribution Task or EAT) ToM also were measured. Thirty-five PD patients and matched HCs also performed the standard Flanker task, as a control measure. In patients, only individuals with high AT scores exhibited a joint Flanker effect, whereas in HCs the joint effect was found irrespectively of AT score. Patients with low EAT scores showed a greater interference effect than patients with high scores, whereas the opposite pattern was found for HCs. In regression analysis AT and EAT scores predicted the Flanker effect in the joint condition only. In the standard task, both groups showed a Flanker effect. The role of different fronto-striatal circuits, especially in PD patients, could explain the different involvement of cognitive and affective ToM in joint tasks. The Flanker effect is discussed considering the referential coding account and the attention-focus account as possible candidates to explain joint action effects.}, } @article {pmid30253811, year = {2018}, author = {Abu-Sbeih, H and Ali, FS and Luo, W and Qiao, W and Raju, GS and Wang, Y}, title = {Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.}, journal = {Journal for immunotherapy of cancer}, volume = {6}, number = {1}, pages = {95}, pmid = {30253811}, issn = {2051-1426}, mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological/*adverse effects/therapeutic use ; Biomarkers ; Biopsy ; Colitis/*diagnosis/*etiology ; Comorbidity ; Disease Management ; *Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*complications/drug therapy/immunology ; Odds Ratio ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.

METHODS: Our study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2 mm, larger than 1 cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.

RESULTS: A total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60 years. Median time from ICPI initiation to IDC was 7 weeks. Fifty-three percent had grade 3-4 diarrhea, and 32% grade 3-4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P = 0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7 days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7 days of IDC onset (P = 0.026 and P = 0.053, respectively). Patients who underwent endoscopy > 30 days of symptom onset required longer duration of steroids (P = 0.02), had more recurrent symptoms (P < 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy ≤30 days (P = 0.03). High-risk features were associated with more frequent (P = 0.03) and longer duration (P = 0.02) hospitalization and infliximab/vedolizumab requirement (P < 0.01). Patients with active histological inflammation had more recurrence (P < 0.01) and repeat endoscopy (P < 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00-1.01; P < 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68-9.01; P < 0.01).

CONCLUSION: High risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.}, } @article {pmid30251340, year = {2019}, author = {Angel, PM and Schwamborn, K and Comte-Walters, S and Clift, CL and Ball, LE and Mehta, AS and Drake, RR}, title = {Extracellular Matrix Imaging of Breast Tissue Pathologies by MALDI-Imaging Mass Spectrometry.}, journal = {Proteomics. Clinical applications}, volume = {13}, number = {1}, pages = {e1700152}, pmid = {30251340}, issn = {1862-8354}, support = {//South Carolina Centers of Economic Excellence SmartState/International ; S10 OD018113/OD/NIH HHS/United States ; //American Cancer Society Institutional Research Grant/International ; S10 OD010731/OD/NIH HHS/United States ; R21 CA207779/CA/NCI NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; P20 GM103542/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*diagnostic imaging/*pathology ; Breast Diseases/diagnostic imaging/pathology ; Disease Progression ; Extracellular Matrix/*metabolism ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; *Molecular Imaging ; Peptides/metabolism ; *Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult ; }, abstract = {PURPOSE: A new method accessing proteins from extracellular matrix by imaging mass spectrometry (ECM IMS) has been recently reported. ECM IMS is evaluated for use in exploring breast tissue pathologies.

EXPERIMENTAL DESIGN: A tissue microarray (TMA) is analyzed that has 176 cores of biopsies and lumpectomies spanning breast pathologies of inflammation, hyperplasia, fibroadenoma, invasive ductal carcinoma, and invasive lobular carcinoma and normal adjacent to tumor (NAT). NAT is compared to subtypes by area under the receiver operating curve (ROC) >0.7. A lumpectomy is also characterized for collagen organization by microscopy and stromal protein distribution by IMS. LC-based high-resolution accurate mass (HRAM) proteomics is used to identify proteins from the lumpectomy.

RESULTS: TMA analysis shows distinct spectral signatures reflecting a heterogeneous tissue microenvironment. Ninety-four peaks show an ROC > 0.7 compared to NAT; NAT has overall higher intensities. Lumpectomy analysis by IMS visualizes a complex central tumor region with distal tumor regions. A total of 39 stromal proteins are identified by HRAM LC-based proteomics. Accurate mass matches between image data and LC-based proteomics demonstrate a heterogeneous collagen type environment in the central tumor.

CONCLUSIONS: Data portray the heterogeneous stromal microenvironment of breast pathologies, including alteration of multiple collagen-type patterns. ECM IMS is a promising new tool for investigating the stromal microenvironment of breast tissue including cancer.}, } @article {pmid30247211, year = {2018}, author = {Cai, M and Feng, G and Zhang, G}, title = {A Case of Radioactivity Concentrated in Orbital Implant in 99mTc-MDP Bone Scan and SPECT/CT.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {12}, pages = {e453-e454}, doi = {10.1097/RLU.0000000000002277}, pmid = {30247211}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Orbital Implants/*adverse effects ; Orbital Neoplasms/*diagnostic imaging/secondary ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; Technetium Tc 99m Medronate ; }, abstract = {A 27-year-old woman, who has received a hydroxyapatite orbital implant in the right eye due to a trauma 6 years ago, was newly diagnosis with left breast invasive ductal carcinoma. Tc-MDP bone scan showed an increased radiotracer accumulation in the right orbit and SPECT/CT confirmed the focal accumulation at the site of the implant, without any sign of local malignant lesions or orbital infection. Radionuclide imaging could provide certain useful information in diagnosing or differential diagnosing orbital disease.}, } @article {pmid30244816, year = {2018}, author = {Hong, YK and McMasters, KM and Egger, ME and Ajkay, N}, title = {Ductal carcinoma in situ current trends, controversies, and review of literature.}, journal = {American journal of surgery}, volume = {216}, number = {5}, pages = {998-1003}, doi = {10.1016/j.amjsurg.2018.06.013}, pmid = {30244816}, issn = {1879-1883}, mesh = {*Breast Neoplasms ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/therapy ; Female ; Humans ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor, non-invasive malignancy confined within the basement membrane of the breast ductal system. There is a wide variation in the natural history of DCIS with an estimated incidence of progression to invasive ductal carcinoma being at least 13%-50% over a range of 10 or more years after initial diagnosis. Regardless of the treatment strategy, long-term survival is excellent. The controversy surrounding DCIS relates to preventing under-treatment, while also avoiding unnecessary treatments. In this article, we review the incidence, presentation, management options and surveillance of DCIS. Furthermore, we address several current controversies related to the management of DCIS, including margin status, sentinel node biopsy, hormonal therapy, the role of radiation in breast conservation surgery, and various risk stratification schemes.}, } @article {pmid30243132, year = {2018}, author = {Nakash, O and Nagar, M and Bentov-Gofrit, D and Md, E and Amiaz, R and Lev-Ran, S and Westen, D}, title = {Validity and clinical utility of DSM and prototype diagnosis for depressive and anxiety spectrum disorders in predicting adaptive functioning.}, journal = {Psychiatry research}, volume = {270}, number = {}, pages = {50-56}, doi = {10.1016/j.psychres.2018.09.010}, pmid = {30243132}, issn = {1872-7123}, mesh = {Adult ; Anxiety Disorders/*diagnosis ; *Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Male ; Middle Aged ; Mood Disorders/*diagnosis ; Psychiatric Status Rating Scales/*standards ; Reproducibility of Results ; }, abstract = {Prototype matching, which involves comparing a patient clinical presentation with a prototype description of the disorder, addresses some of the clinical limitations of categorical approaches. Most research to-date on prototype matching has been conducted with personality disorders. Here, we examined the validity and clinical utility of prototype diagnosis for mood and anxiety disorders. We compared clinicians prototype diagnosis (based on DSM IV and empirically derived) to categorical diagnosis (based on independent SCID interview) in predicting patient global adaptive functioning rated across the clinician, patient and independent interviewer among N = 80 clinicians and N = 170 patients. Our findings show that prototype diagnosis (both one that is based on DSM criteria and empirically derived) demonstrates some incremental validity over and above the categorical DSM IV, in predicting patient's global adaptive functioning. This is particularly pronounced for mood disorders (MDD and dysthymia) as well as several anxiety disorders (OCD, social phobia) across a range of experience level of diagnosticians. Furthermore, clinicians rated the prototype matching approach as more useful in clinical practice compared with the binary categorical system. Using a dimensional approach, which is based on prototype matching that also preserves the advantages of categorical system offers a valid and efficient approach to psychiatric assessment.}, } @article {pmid30241034, year = {2018}, author = {Jung, M and Maldonado, J and Schwartz, MR and Sneige, N and Ayala, AG and Ro, JY}, title = {Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation.}, journal = {Annals of diagnostic pathology}, volume = {37}, number = {}, pages = {42-46}, doi = {10.1016/j.anndiagpath.2018.09.001}, pmid = {30241034}, issn = {1532-8198}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*pathology ; Female ; Humans ; }, abstract = {Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.}, } @article {pmid30236106, year = {2018}, author = {Schultz, S and Bartsch, H and Sotlar, K and Petat-Dutter, K and Bonin, M and Kahlert, S and Harbeck, N and Vogel, U and Seeger, H and Fehm, T and Neubauer, HJ}, title = {Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers.}, journal = {BMC medical genomics}, volume = {11}, number = {1}, pages = {80}, pmid = {30236106}, issn = {1755-8794}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Formaldehyde/chemistry ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Paraffin Embedding ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC.

METHODS: Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR.

RESULTS: Multiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P < 0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours.

CONCLUSION: We confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.}, } @article {pmid30234498, year = {2018}, author = {Matter, M and Nenoff, L and Meier, G and Weber, DC and Lomax, AJ and Albertini, F}, title = {Alternatives to patient specific verification measurements in proton therapy: a comparative experimental study with intentional errors.}, journal = {Physics in medicine and biology}, volume = {63}, number = {20}, pages = {205014}, doi = {10.1088/1361-6560/aae2f4}, pmid = {30234498}, issn = {1361-6560}, mesh = {Humans ; *Precision Medicine ; *Proton Therapy ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/*methods ; *Radiotherapy Setup Errors ; Radiotherapy, Intensity-Modulated ; }, abstract = {Patient specific verification (PSV) measurements for pencil beam scanning (PBS) proton therapy are resource-consuming and necessitate substantial beam time outside of clinical hours. As such, efforts to safely reduce the PSV-bottleneck in the clinical work-flow are of great interest. Here, capabilities of current PSV methods to ensure the treatment integrity were investigated and compared to an alternative approach of reconstructing the dose distribution directly from the machine control- or delivery log files with the help of an independent dose calculation (IDC). Scenarios representing a wide range of delivery or work-flow failures were identified (e.g. error in spot position, air gap or pre-absorber setting) and machine files were altered accordingly. This yielded 21 corrupted treatment files, which were delivered and measured with our clinical PSV protocol. IDC machine- and log file checks were also conducted and their sensitivity at detecting the errors compared to the measurements. Although some of the failure scenarios induced clinically relevant dose deviations in the patient geometry, the PSV measurement protocol only detected one out of 21 error scenarios. However, 11 and all 21 error scenarios were detected using dose reconstructions based on the log and machine files respectively. Our data suggests that, although commonly used in particle therapy centers, PSV measurements do a poor job detecting data transfer failures and imperfect delivery machine performance. Machine- and log-file IDCs have been shown to successfully detect erroneous work-flows and to represent a reliable addition to the QA procedure, with the potential to replace PSV.}, } @article {pmid30228172, year = {2018}, author = {Tasdemir, N and Bossart, EA and Li, Z and Zhu, L and Sikora, MJ and Levine, KM and Jacobsen, BM and Tseng, GC and Davidson, NE and Oesterreich, S}, title = {Comprehensive Phenotypic Characterization of Human Invasive Lobular Carcinoma Cell Lines in 2D and 3D Cultures.}, journal = {Cancer research}, volume = {78}, number = {21}, pages = {6209-6222}, pmid = {30228172}, issn = {1538-7445}, support = {R00 CA193734/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; K99 CA193734/CA/NCI NIH HHS/United States ; F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA203055/CA/NCI NIH HHS/United States ; F30 CA203095/CA/NCI NIH HHS/United States ; }, mesh = {Adherens Junctions ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/metabolism ; Carcinoma, Lobular/*metabolism/pathology ; Cell Adhesion ; *Cell Culture Techniques ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Collagen Type I/metabolism ; Extracellular Matrix/metabolism ; Female ; Humans ; Neoplasm Invasiveness ; Phenotype ; Receptors, Estrogen/metabolism ; Signal Transduction ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histologic and clinical features, ILC still remains a chronically understudied disease, with limited knowledge gleaned from available laboratory research models. Here we report a comprehensive 2D and 3D phenotypic characterization of four estrogen receptor-positive human ILC cell lines: MDA-MB-134, SUM44, MDA-MB-330, and BCK4. Compared with the IDC cell lines MCF7, T47D, and MDA-MB-231, ultra-low attachment culture conditions revealed remarkable anchorage independence unique to ILC cells, a feature not evident in soft-agar gels. Three-dimensional Collagen I and Matrigel culture indicated a generally loose morphology for ILC cell lines, which exhibited differing preferences for adhesion to extracellular matrix proteins in 2D. Furthermore, ILC cells were limited in their ability to migrate and invade in wound-scratch and transwell assays, with the exception of haptotaxis to Collagen I. Transcriptional comparison of these cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism, and alternative cell adhesion molecules such as N-cadherin, some of which were differentially regulated in ILC versus IDC tumors. Altogether, these studies provide an invaluable resource for the breast cancer research community and facilitate further functional discoveries toward understanding ILC, identifying novel drug targets, and ultimately improving the outcome of patients with ILC.Significance: These findings provide the breast cancer research community with a comprehensive assessment of human invasive lobular carcinoma (ILC) cell line signaling and behavior in various culture conditions, aiding future endeavors to develop therapies and to ultimately improve survival in patients with ILC. Cancer Res; 78(21); 6209-22. ©2018 AACR.}, } @article {pmid30227836, year = {2018}, author = {Jouali, F and Marchoudi, N and Talbi, S and Bilal, B and El Khasmi, M and Rhaissi, H and Fekkak, J}, title = {Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {900}, pmid = {30227836}, issn = {1471-2407}, mesh = {Adult ; Aged ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Exons/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Middle Aged ; Morocco/epidemiology ; Oncogene Protein v-akt/*genetics ; PTEN Phosphohydrolase/*genetics ; Retrospective Studies ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/epidemiology/*genetics/pathology ; }, abstract = {BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.

METHODS: We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.

RESULTS: All patients were female with a median age of 46 years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.

CONCLUSION: The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.}, } @article {pmid30223818, year = {2018}, author = {Doering, S and Blüml, V and Parth, K and Feichtinger, K and Gruber, M and Aigner, M and Rössler-Schülein, H and Freidl, M and Wininger, A}, title = {Personality functioning in anxiety disorders.}, journal = {BMC psychiatry}, volume = {18}, number = {1}, pages = {294}, pmid = {30223818}, issn = {1471-244X}, mesh = {Adult ; Anxiety Disorders/*psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Male ; Middle Aged ; Panic Disorder/*psychology ; *Personality ; Personality Disorders/*diagnosis ; Personality Tests ; Phobic Disorders/*psychology ; }, abstract = {BACKGROUND: The Alternative DSM-5 Model for Personality Disorders as well as the upcoming IDC-11 have established a new focus on diagnosing personality disorders (PD): personality functioning. An impairment of self and interpersonal functioning in these models represents a general diagnostic criterion for a personality disorder. Little is known so far about the impairment of personality functioning in patients with other mental disorders than PD. This study aims to assess personality functioning in patients with anxiety disorders.

METHODS: Ninety-seven patients with the diagnosis of generalized anxiety disorder, panic disorder, or phobia, and 16 healthy control persons were diagnosed using the Structured Clinical Interview for DSM-IV (SCID-I and -II) and were assessed by means of the Structured Interview for Personality Organization (STIPO) to determine the level of personality functioning.

RESULTS: While all three patient groups showed significant impairment in personality functioning compared to the control group, no significant differences were observed between the different patient groups. In all three groups of anxiety disorders patients with comorbid PD showed significantly worse personality functioning than patients without. Patients without comorbid PD also yielded a significant impairment in their personality functioning when compared to the control group.

CONCLUSIONS: Anxiety disorders are associated with a significant impairment in personality functioning, which is significantly increased by comorbid PD. There are no differences in terms of personality functioning between patients with different anxiety disorders.}, } @article {pmid30214581, year = {2018}, author = {Liu, W and Wu, J and Shi, G and Yue, X and Liu, D and Zhang, Q}, title = {Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic biomarker for patients with breast cancer.}, journal = {Oncology letters}, volume = {16}, number = {4}, pages = {4462-4470}, pmid = {30214581}, issn = {1792-1074}, abstract = {Protocadherin-10 (PCDH10) is a tumor suppressor gene. Its expression level is downregulated by promoter methylation in certain types of human tumors. The aim of the present study was to examine the expression level and promoter methylation status of PCDH10 in breast cancer cells and to evaluate the association of PCDH10 methylation and tumor progression and prognosis. MethyLight was used to detect the methylation status of PCDH10 in breast cancer tissues and healthy breast tissues. Reverse transcription-quantitative polymerase chain reaction was used to assess the mRNA expression level of PCDH10, as well as to evaluate the association between PCDH10 methylation and clinicopathological features, along with patients' overall survival (OS). PCDH10 5'-C-phosphate-G-3' (CpG) methylated sites were identified in tumor tissues and matched healthy tissues (n=392). Tumor tissues and matched healthy tissues exhibited identifiable PCR results, with PCDH10 gene promoter methylation identified in ductal carcinoma in situ (66%), invasive ductal carcinoma (82%), invasive ductal carcinoma with lymph node metastasis (85.32%) and hereditary breast cancer tissues (72.37%). PCDH10 mRNA expression was significantly decreased in breast cancer tissues compared with healthy breast tissues (P=0.032). PCDH10 methylation was associated with tumor size (P=0.004), but not associated with other clinical factors. Survival analysis revealed that the patients exhibiting methylated-PCDH10 had significantly poorer OS times than patients exhibiting unmethylated-PCDH10 (P<0.0001). Receiver operating characteristic analysis indicated a sensitivity of 75%, a specificity of 62.5%, and an area under the curve of 0.682 for PCDH10. Additionally, the results of the present study indicated that PCDH10 methylation status may be a useful diagnostic and prognostic evaluation biomarker for breast cancer. The results suggested that PCDH10 methylation is a common occurrence in primary breast cancer and is associated with poor survival rates among patients with breast cancer.}, } @article {pmid30211313, year = {2018}, author = {Rawat, RR and Ruderman, D and Macklin, P and Rimm, DL and Agus, DB}, title = {Correlating nuclear morphometric patterns with estrogen receptor status in breast cancer pathologic specimens.}, journal = {NPJ breast cancer}, volume = {4}, number = {}, pages = {32}, pmid = {30211313}, issn = {2374-4677}, abstract = {In this pilot study, we introduce a machine learning framework to identify relationships between cancer tissue morphology and hormone receptor pathway activation in breast cancer pathology hematoxylin and eosin (H&E)-stained samples. As a proof-of-concept, we focus on predicting clinical estrogen receptor (ER) status-defined as greater than one percent of cells positive for estrogen receptor by immunohistochemistry staining-from spatial arrangement of nuclear features. Our learning pipeline segments nuclei from H&E images, extracts their position, shape and orientation descriptors, and then passes them to a deep neural network to predict ER status. After training on 57 tissue cores of invasive ductal carcinoma (IDC), our pipeline predicted ER status in an independent test set of patient samples (AUC ROC = 0.72, 95%CI = 0.55-0.89, n = 56). This proof of concept shows that machine-derived descriptors of morphologic histology patterns can be correlated to signaling pathway status. Unlike other deep learning approaches to pathology, our system uses deep neural networks to learn spatial relationships between pre-defined biological features, which improves the interpretability of the system and sheds light on the features the neural network uses to predict ER status. Future studies will correlate morphometry to quantitative measures of estrogen receptor status and, ultimately response to hormonal therapy.}, } @article {pmid30210925, year = {2018}, author = {Dai, D and Jin, H and Wang, X}, title = {Nomogram for predicting survival in triple-negative breast cancer patients with histology of infiltrating duct carcinoma: a population-based study.}, journal = {American journal of cancer research}, volume = {8}, number = {8}, pages = {1576-1585}, pmid = {30210925}, issn = {2156-6976}, abstract = {Triple-negative breast cancer (TNBC) represents around 15%-20% of newly diagnosed breast cancer and is more aggressive than other breast cancer sub-types. Infiltrating duct carcinoma (IDC) is the most common type of TNBC. Nomogram is a valuable tool for prognosis prediction by integrating different biological and clinical variables. The purpose of current study was to evaluate the prognostic value of clinical factors of TNBC patients with IDC histology type and construct nomograms for their outcome prediction. The cohort was selected from Surveillance, Epidemiology, and End Results (SEER) program. Univariate and multivariate analyses were performed using Cox proportional hazards regression model to evaluate the prognostic value of involved variables. Nomogram was constructed from the multivariate logistic regression model to combine all the prognostic factors to predict the 1-year and 3-year prognosis of TNBC patients with histology of IDC. Internal validation of nomogram was tested by discrimination and calibration. We identified 14,538 patients with the median and max survival time was 28 months and 59 months, respectively. There were 1,592 deaths, accounting for 10.9% of the cohort. Multivariate analyses showed that grade, tumor stage, tumor size, regional nodes positive, marital status, experience of radiotherapy or chemotherapy were independent prognostic factors of IDC of TNBC. Eleven variables were combined to construct 1-year and 3-year nomograms. It was revealed that the C-index of the nomograms was 0.763 and the calibration curves showed good agreement between the nomogram prediction and actual observation. Current study was the first one to construct nomograms of TNBC patients with IDC histology, which could help physicians to identify patients at high risk for intensive treatment or follow-up.}, } @article {pmid30208914, year = {2018}, author = {Kinj, R and Chand, ME and Gal, J and Gautier, M and Montagné, L and Lam Cham Kee, D and Hannoun-Lévi, JM}, title = {Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome.}, journal = {Radiation oncology (London, England)}, volume = {13}, number = {1}, pages = {174}, pmid = {30208914}, issn = {1748-717X}, mesh = {Aged ; Aged, 80 and over ; Brachytherapy/*methods ; Breast Neoplasms/mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB).

METHODS: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician.

RESULTS: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 40 months (range: 36-42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.

CONCLUSION: We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed.}, } @article {pmid30208271, year = {2018}, author = {Nuñez, NN and Khuu, C and Babu, CS and Bertolani, SJ and Rajavel, AN and Spear, JE and Armas, JA and Wright, JD and Siegel, JB and Lim, C and David, SS}, title = {The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn[2+] Ligands and Roles in Damage Recognition and Repair.}, journal = {Journal of the American Chemical Society}, volume = {140}, number = {41}, pages = {13260-13271}, pmid = {30208271}, issn = {1520-5126}, support = {R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Binding Sites ; Cysteine/chemistry ; DNA Glycosylases/chemistry/genetics/*metabolism ; Geobacillus stearothermophilus/enzymology ; Humans ; Ligands ; Mice ; Mutation ; Protein Binding ; Sequence Alignment ; Zinc/*metabolism ; }, abstract = {The DNA base excision repair (BER) glycosylase MUTYH prevents DNA mutations by catalyzing adenine (A) excision from inappropriately formed 8-oxoguanine (8-oxoG):A mismatches. The importance of this mutation suppression activity in tumor suppressor genes is underscored by the association of inherited variants of MUTYH with colorectal polyposis in a hereditary colorectal cancer syndrome known as MUTYH-associated polyposis, or MAP. Many of the MAP variants encompass amino acid changes that occur at positions surrounding the two-metal cofactor-binding sites of MUTYH. One of these cofactors, found in nearly all MUTYH orthologs, is a [4Fe-4S][2+] cluster coordinated by four Cys residues located in the N-terminal catalytic domain. We recently uncovered a second functionally relevant metal cofactor site present only in higher eukaryotic MUTYH orthologs: a Zn[2+] ion coordinated by three Cys residues located within the extended interdomain connector (IDC) region of MUTYH that connects the N-terminal adenine excision and C-terminal 8-oxoG recognition domains. In this work, we identified a candidate for the fourth Zn[2+] coordinating ligand using a combination of bioinformatics and computational modeling. In addition, using in vitro enzyme activity assays, fluorescence polarization DNA binding assays, circular dichroism spectroscopy, and cell-based rifampicin resistance assays, the functional impact of reduced Zn[2+] chelation was evaluated. Taken together, these results illustrate the critical role that the "Zn[2+] linchpin motif" plays in MUTYH repair activity by providing for proper engagement of the functional domains on the 8-oxoG:A mismatch required for base excision catalysis. The functional importance of the Zn[2+] linchpin also suggests that adjacent MAP variants or exposure to environmental chemicals may compromise Zn[2+] coordination, and ability of MUTYH to prevent disease.}, } @article {pmid30198850, year = {2018}, author = {Chancy, M and Gónzalez, V and Cabrales, M and Lopera, C and García, HI}, title = {[Radical post-prostatectomy biochemical relapse in patients with pathological factors treated with adjuvant versus observation radiotherapy in Colombia.].}, journal = {Archivos espanoles de urologia}, volume = {71}, number = {7}, pages = {588-594}, pmid = {30198850}, issn = {0004-0614}, mesh = {Aged ; Colombia ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/blood ; Prostate-Specific Antigen/blood ; *Prostatectomy ; Prostatic Neoplasms/blood/*radiotherapy/*surgery ; Radiotherapy, Adjuvant ; Retrospective Studies ; *Watchful Waiting ; }, abstract = {OBJECTIVE: In patients with prostate cancer and high-risk pathological factors, adjuvant radiotherapy (ART) has been reported to be superior to observation for local disease control and progressionfree survival. But more than 30% of the patients do not present biochemical relapse (BR) and therefore the ART associated with the toxicity can be avoided. It has not been determined whether close observation with early salvage radiotherapy provides a similar result to ART.

METHODS: Patients with localized prostate cancer treated with radical prostatectomy (RP) at the Institute of Cancerology (Medellín-Colombia), and those who had adverse predictors of biochemical relapse were included: extracapsular compromise, seminal vesicle involvement (pT3), and positive surgical margins (PSM) or not. Biochemical progression-free survival was compared between ART group and the observation group.

RESULTS: Of 171 patients treated with RP, 55 had at least one adverse pathological factor. Of them, 33 (60%) were observed and 22 (40%) received ART. The median follow-up was 55 months (IQR: 37-89). Biochemical relapse occurred in 6 (18.2%) of the first group and 3 (13.6%) of the second group (p>0.05). Biochemical progression-free survival was 24.2% (95%CI: 11.5%-39.6%) in the observation group and 47.7% (95CI: 26.3%-66.4%) in the ART.

CONCLUSIONS: After radical prostatectomy, the biochemical relapse in the patient with high-risk prostate cancer was similar in the observation group and in the ART group.}, } @article {pmid30195866, year = {2018}, author = {Lee, JH and Parveen, A and Do, MH and Lim, Y and Shim, SH and Kim, SY}, title = {Lespedeza cuneata protects the endothelial dysfunction via eNOS phosphorylation of PI3K/Akt signaling pathway in HUVECs.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {48}, number = {}, pages = {1-9}, doi = {10.1016/j.phymed.2018.05.005}, pmid = {30195866}, issn = {1618-095X}, mesh = {Cell Survival/drug effects ; Chromones ; Human Umbilical Vein Endothelial Cells/*drug effects/metabolism ; Humans ; Lespedeza/*chemistry ; Morpholines ; NG-Nitroarginine Methyl Ester ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protective Agents/*pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/*drug effects ; Vascular Diseases/metabolism ; }, abstract = {BACKGROUND: Lespedeza cuneata G.Don (LCE), which belongs to the genus Lespedeza (Leguminosae), is a traditional oriental medicine known to prevent diabetes and cardiovascular diseases. However, no scientific studies about the effectiveness of LCE, their responsible bioactive constituents, and its mechanisms against endothelial dysfunction have been performed.

PURPOSE: This study was performed to investigate the role of LCE and its chemical components in ameliorating endothelial dysfunction.

METHODS: The production of nitric oxide (NO) was evaluated after LCE treatment in HUVECs. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Western blot analysis was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase B (PKB, also known as Akt) in human umbilical vein endothelial cells (HUVECs).

RESULTS: Pretreatment with L-NAME and LY294002 significantly decreased the LCE-induced NO production, as well as eNOS and Akt phosphorylation. β-Sitosterol and β-Sitosterol 6'-linolenoyl-3-O-β-D-glucopyranoside are the bioactive constituents increase NO production as well as eNOS phosphorylation.

CONCLUSION: Our findings suggest that LCE increase NO production via eNOS phosphorylation of PI3K/Akt signaling pathway.}, } @article {pmid30194658, year = {2018}, author = {Sinha, VC and Piwnica-Worms, H}, title = {Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {23}, number = {4}, pages = {191-205}, pmid = {30194658}, issn = {1573-7039}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; W81XWH-17-1-0077//Department of Defense through the Breast Cancer Research Program/International ; }, mesh = {Animals ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Early Detection of Cancer/methods ; Female ; Humans ; Mammography/methods ; Tumor Microenvironment/physiology ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-invasive proliferative growth in the breast that serves as a non-obligate precursor to invasive ductal carcinoma. The widespread adoption of screening mammography has led to a steep increase in the detection of DCIS, which now comprises approximately 20% of new breast cancer diagnoses in the United States. Interestingly, the intratumoral heterogeneity (ITH) that has been observed in invasive breast cancers may have been established early in tumorigenesis, given the vast and varied ITH that has been detected in DCIS. This review will discuss the intratumoral heterogeneity of DCIS, focusing on the phenotypic and genomic heterogeneity of tumor cells, as well as the compositional heterogeneity of the tumor microenvironment. In addition, we will assess the spatial heterogeneity that is now being appreciated in these lesions, and summarize new approaches to evaluate heterogeneity of tumor and stromal cells in the context of their spatial organization. Importantly, we will discuss how a growing understanding of ITH has led to a more holistic appreciation of the complex biology of DCIS, specifically its evolution and natural history. Finally, we will consider ways in which our knowledge of DCIS ITH might be translated in the future to guide clinical care for DCIS patients.}, } @article {pmid30190699, year = {2018}, author = {Feniger-Schaal, R and Hart, Y and Lotan, N and Koren-Karie, N and Noy, L}, title = {The Body Speaks: Using the Mirror Game to Link Attachment and Non-verbal Behavior.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {1560}, pmid = {30190699}, issn = {1664-1078}, abstract = {The Mirror Game (MG) is a common exercise in dance/movement therapy and drama therapy. It is used to promote participants' ability to enter and remain in a state of togetherness. In spite of the wide use of the MG by practitioners, it is only recently that scientists begun to use the MG in research, examining its correlates, validity, and reliability. This study joins this effort by reporting on the identification of scale items to describe the non-verbal behavior expressed during the MG and its correlation to measures of attachment. Thus, we explored the application of the MG as a tool for assessing the embodiment of attachment in adulthood. Forty-eight participants (22 females, mean age = 33.2) played the MG with the same gender-matched expert players. All MG were videotaped. In addition, participants were evaluated on two central measurements of attachment in adulthood: The Adult Attachment Interview (AAI) and the Experience in Close Relationship questionnaire (ECR). To analyze the data, we developed the "MG scale" that coded the non-verbal behavior during the movement interaction, using 19 parameters. The sub-scales were reduced using factor analysis into two dimensions referred to as "together" and "free." The free factor was significantly correlated to both measurements of attachment: Participants classified as having secure attachment on the AAI, received higher scores on the MG free factor than participants classified as insecure [t(46) = 7.858, p = 0.000]. Participants, who were high on the avoidance dimension on the ECR, were low on the MG free factor [r(48) = -0.285, p = 0.007]. This is the first study to examine the MG as it is used by practitioners and its correlation to highly standardized measures. This exploratory study may be considered as part of the first steps of exploring the MG as a standardized assessment tool. The advantages of the MG as a simple, non-verbal movement interaction demonstrate some of the strengths of dance/movement and drama therapy practice.}, } @article {pmid30185420, year = {2019}, author = {Lee, JY and Schizas, M and Geyer, FC and Selenica, P and Piscuoglio, S and Sakr, RA and Ng, CKY and Carniello, JVS and Towers, R and Giri, DD and de Andrade, VP and Papanastasiou, AD and Viale, A and Harris, RS and Solit, DB and Weigelt, B and Reis-Filho, JS and King, TA}, title = {Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {2}, pages = {674-686}, pmid = {30185420}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Breast Carcinoma In Situ/*genetics/*pathology ; Carcinoma, Lobular/*genetics/*pathology ; Clonal Evolution/*genetics ; Disease Progression ; *Genetic Heterogeneity ; *Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasm Metastasis ; Neoplasm Staging ; Tumor Burden ; Exome Sequencing ; }, abstract = {PURPOSE: Lobular carcinoma in situ (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.Experimental Design: We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas in situ (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.

RESULTS: WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with CDH1 mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.

CONCLUSIONS: Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions.}, } @article {pmid30185184, year = {2018}, author = {Du, JJ and Chen, YF and Peng, Y and Li, XJ and Ma, W}, title = {Calcification of the intervertebral disc and ossification of posterior longitudinal ligament in children.}, journal = {BMC musculoskeletal disorders}, volume = {19}, number = {1}, pages = {316}, pmid = {30185184}, issn = {1471-2474}, support = {81501929//National Natural Science Foundation of China/ ; No. Z161100000116057//Beijing Municipal Science and Technology Commission/ ; }, mesh = {Adolescent ; Calcinosis/*complications/*diagnostic imaging/therapy ; Cervical Vertebrae/*diagnostic imaging ; Child ; Conservative Treatment ; Humans ; Male ; Neck Pain/diagnostic imaging/etiology/therapy ; Ossification of Posterior Longitudinal Ligament/*complications/*diagnostic imaging/therapy ; }, abstract = {BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL of the cervical spine mainly affect people ages 50-70 years. The coexistence of IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow-up were reported to date.

CASE PRESENTATION: A 6-year-old boy presented with complains of neck pain at July 2007. The boy was treated by conservative treatment and observed up for 9 years. Neck pain greatly improved after a one-month conservative treatment and never recur. Laboratory tests revealed elevated ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow-up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4 and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9-year follow-up. Nineteen months after initial diagnosis, restoration of T2-weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal intensity of C3/4 disc was observed at 9-year follow-up.

CONCLUSIONS: IDC with OPLL in children is very rare. Conservative treatments are recommended with affirmative short-term and long-term clinical effects. More intensive observation with long-term follow-ups may be needed to warrant the clinical effects.}, } @article {pmid30183588, year = {2018}, author = {Abdalla, AS and Lazarevska, A and Omer, MM and Tan, E and Asaad, A and Sathananthan, S}, title = {Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding During Chemotherapy: A Case Report and Literature Review.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {113}, number = {4}, pages = {564-570}, doi = {10.21614/chirurgia.113.4.564}, pmid = {30183588}, issn = {1221-9118}, mesh = {Antineoplastic Agents/*adverse effects ; Breast Neoplasms/complications/drug therapy/*secondary ; Female ; Humans ; Uterine Cervical Neoplasms/complications/*secondary ; Uterine Hemorrhage/chemically induced/*etiology ; }, abstract = {The most common sites of invasive breast cancer metastasis are the lungs, liver, bones and brain. Less frequent sites include the gastrointestinal tract, pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The uterus is reported as a rare site for metastasis, and even more so for an isolated metastasis. Other sites of extra-genital sources for uterine metastases include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma, urinary bladder and thyroid. The rarity of breast cancer metastasis to the uterine cervix could be explained by the fact that the cervix has a small blood supply and an afferent lymph drainage system alone. It is rare to diagnose a cervical metastasis prior to eliciting the primary breast disease. Invasive lobular carcinoma metastasises to the female reproductive system more frequently than invasive ductal carcinoma. This paper presents a case of breast cancer metastasis to the cervix.}, } @article {pmid30178199, year = {2018}, author = {Sarikaya, I and Sharma, P and Sarikaya, A}, title = {F-18 fluoride uptake in primary breast cancer.}, journal = {Annals of nuclear medicine}, volume = {32}, number = {10}, pages = {678-686}, doi = {10.1007/s12149-018-1294-4}, pmid = {30178199}, issn = {1864-6433}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biological Transport ; Breast Neoplasms/diagnostic imaging/*metabolism ; Female ; Fluorides/*pharmacokinetics ; *Fluorine Radioisotopes ; Humans ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; }, abstract = {OBJECTIVE: Bone-specific radiotracers are known to accumulate in breast lesions. Tc-99m diphosphonates have been widely studied in differentiating breast lesions. In this retrospective study, we aimed to assess the uptake of the bone-specific PET radiotracer, F-18 fluoride (NaF), in primary breast cancers to determine its sensitivity and to identify any differences in NaF uptake between calcified and non-calcified tumors, histological subtypes, and patients with or without axillary lymphadenopathy.

METHODS: NaF positron emission tomography/computed tomography (PET/CT) images of 69 newly diagnosed breast cancer patients were reviewed. F-18 fluoride uptake as maximum standardized uptake value (NaF SUVmax) was measured in the primary tumor, enlarged axillary lymph nodes and contralateral normal/non-tumoral breast tissue. Low-dose CT images were reviewed to locate the primary tumor and grossly assess its calcification and check for ipsilateral axillary lymphadenopathy. Whole body NaF PET/CT images were reviewed to search for bone metastases. Eighteen patients also underwent F-18 fluorodeoxyglucose (FDG) PET/CT study.

RESULTS: The primary breast tumor was clearly seen as focal or diffuse uptake on NaF PET images in 27 of 69 patients (39%) (mean NaF SUVmax: 2.0 ± 1.0). In the rest, there was only mild bilateral diffuse breast uptake. When analyzing images per histological subtype (42 patients, 43 tumors), 14 of 31 invasive ductal carcinomas (IDC) (45%) and 3 of 4 ductal carcinoma in situ (DCIS) were visible on PET. Five invasive lobular carcinomas, 2 invasive mammary carcinomas, and 1 mucinous carcinoma were not visible on PET. Mean NaF SUVmax of contralateral normal/non-tumoral breast tissue was 1.0 ± 0.4. There was no significant difference in mean NaF SUVmax of primary tumor in cases with and without calcification or with and without axillary lymphadenopathy (p 0.892 and 0.957). There was no correlation between NaF SUVmax and FDG SUVmax values of the primary tumors (r 0.072, p 0.797, Pearson correlation).

CONCLUSION: NaF PET has relatively low sensitivity in detecting breast cancer. However, abnormal breast uptake on NaF PET requires further evaluation. F-18 fluoride uptake in the primary breast tumor does not seem to be correlated with axillary lymphadenopathy (metastasis potential), gross tumor calcification or metabolic activity of the tumor.}, } @article {pmid30172938, year = {2018}, author = {Kim, SY and Kim, EK and Moon, HJ and Yoon, JH and Koo, JS and Kim, SG and Kim, MJ}, title = {Association among T2 signal intensity, necrosis, ADC and Ki-67 in estrogen receptor-positive and HER2-negative invasive ductal carcinoma.}, journal = {Magnetic resonance imaging}, volume = {54}, number = {}, pages = {176-182}, pmid = {30172938}, issn = {1873-5894}, support = {P41 EB017183/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/metabolism ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Necrosis ; Observer Variation ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {PURPOSE: To determine whether T2 signal intensity, necrosis, and ADC values are associated with Ki-67 in patients with Estrogen Receptor (ER)-positive and Human epidermal growth factor receptor type 2 (HER2)-negative invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: Between March 2012 and February 2013, one hundred eighty seven women with ER-positive and HER2-negative IDC who underwent breast MRI and subsequent surgery were included. Intratumoral signal intensity was evaluated based on a combination of T2-weighted (low or equal, high, or very high) and contrast-enhanced MR images (enhancement or not). Necrosis was defined as very high T2 and no enhancement. Using the analysis of variance and pairwise t-test, a model based on intratumoral signal intensity was developed to assess Ki-67 of the surgical specimen. Inter-observer agreement for the developed model was analyzed. Conventional mean and minimum apparent diffusion coefficient (ADC) measurements were performed and correlated with Ki-67.

RESULTS: As the grade of the developed model increased (Grade I: low or equal T2, Grade II: high T2, or necrosis < 50%, Grade III: necrosis ≥ 50%), mean Ki-67 significantly increased (Grade I to III: 12.5%, 17.6%, 45.0%, respectively; P < 0.001). Good inter-observer agreement was found for the model (κ = 0.846, P < 0.001). ADC did not show significant correlations with Ki-67 (Pearson's correlation coefficient, 0.140 [P = 0.057] for mean ADC; -0.079 [P = 0.284] for minimum ADC).

CONCLUSION: Intratumoral signal intensity but not ADC was associated with Ki-67 in patients with ER-positive and HER2-negative IDC.}, } @article {pmid30171046, year = {2019}, author = {Hess, J and Unger, K and Maihoefer, C and Schüttrumpf, L and Wintergerst, L and Heider, T and Weber, P and Marschner, S and Braselmann, H and Samaga, D and Kuger, S and Pflugradt, U and Baumeister, P and Walch, A and Woischke, C and Kirchner, T and Werner, M and Werner, K and Baumann, M and Budach, V and Combs, SE and Debus, J and Grosu, AL and Krause, M and Linge, A and Rödel, C and Stuschke, M and Zips, D and Zitzelsberger, H and Ganswindt, U and Henke, M and Belka, C}, title = {A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {25}, number = {5}, pages = {1505-1516}, doi = {10.1158/1078-0432.CCR-18-0776}, pmid = {30171046}, issn = {1557-3265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; *Biomarkers, Tumor ; Female ; Head and Neck Neoplasms/*etiology/*mortality/pathology/therapy ; Humans ; Kaplan-Meier Estimate ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Papillomaviridae ; Papillomavirus Infections/complications ; Prognosis ; Proportional Hazards Models ; *Transcriptome ; Treatment Outcome ; }, abstract = {PURPOSE: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.

EXPERIMENTAL DESIGN: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA-mRNA target network was generated and analyzed.

RESULTS: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98-9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).

CONCLUSIONS: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.}, } @article {pmid30170496, year = {2018}, author = {Porcari, AM and Zhang, J and Garza, KY and Rodrigues-Peres, RM and Lin, JQ and Young, JH and Tibshirani, R and Nagi, C and Paiva, GR and Carter, SA and Sarian, LO and Eberlin, MN and Eberlin, LS}, title = {Multicenter Study Using Desorption-Electrospray-Ionization-Mass-Spectrometry Imaging for Breast-Cancer Diagnosis.}, journal = {Analytical chemistry}, volume = {90}, number = {19}, pages = {11324-11332}, pmid = {30170496}, issn = {1520-6882}, support = {R00 CA190783/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*diagnostic imaging/metabolism ; Female ; Humans ; *Molecular Imaging ; Racial Groups ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Spectrometry, Mass, Electrospray Ionization ; }, abstract = {The histological and molecular subtypes of breast cancer demand distinct therapeutic approaches. Invasive ductal carcinoma (IDC) is subtyped according to estrogen-receptor (ER), progesterone-receptor (PR), and HER2 status, among other markers. Desorption-electrospray-ionization-mass-spectrometry imaging (DESI-MSI) is an ambient-ionization MS technique that has been previously used to diagnose IDC. Aiming to investigate the robustness of ambient-ionization MS for IDC diagnosis and subtyping over diverse patient populations and interlaboratory use, we report a multicenter study using DESI-MSI to analyze samples from 103 patients independently analyzed in the United States and Brazil. The lipid profiles of IDC and normal breast tissues were consistent across different patient races and were unrelated to country of sample collection. Similar experimental parameters used in both laboratories yielded consistent mass-spectral data in mass-to-charge ratios (m/ z) above 700, where complex lipids are observed. Statistical classifiers built using data acquired in the United States yielded 97.6% sensitivity, 96.7% specificity, and 97.6% accuracy for cancer diagnosis. Equivalent performance was observed for the intralaboratory validation set (99.2% accuracy) and, most remarkably, for the interlaboratory validation set independently acquired in Brazil (95.3% accuracy). Separate classification models built for ER and PR statuses as well as the status of their combined hormone receptor (HR) provided predictive accuracies (>89.0%), although low classification accuracies were achieved for HER2 status. Altogether, our multicenter study demonstrates that DESI-MSI is a robust and reproducible technology for rapid breast-cancer-tissue diagnosis and therefore is of value for clinical use.}, } @article {pmid30155255, year = {2018}, author = {Goto, Y and Yoshida, T and Kimura, M}, title = {Higher efficacy and complete response with administration of eribulin for recurrent squamous cell breast carcinoma: A case report.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {3}, pages = {318-320}, pmid = {30155255}, issn = {2049-9450}, abstract = {Squamous cell carcinoma is a rare histological type of breast cancer classified as metaplastic carcinoma. Metaplastic carcinoma involves differentiation of the breast glandular duct cells into mesenchymal tissues. While the chemotherapy regimen for metaplastic carcinoma is often similar to that for invasive ductal carcinoma, recurrence is associated with a poor prognosis due to the inadequate therapeutic efficacy of the regimen. We herein present the case of a 42-year-old female patient who underwent mastectomy of the right breast and right axillary node lymphadenectomy for T4N3aM0 breast cancer stage. The cancer was histopathologically diagnosed as squamous cell carcinoma of the breast. Adjuvant cyclophosphamide-epirubicin-fluorouracil (CEF) postoperative chemotherapy was administered, and lymphadenectomy of right-sided parasternal lymphatic metastases with pleural drainage was subsequently performed. Radiotherapy was administered to the thoracic wall and supraclavicular lymph nodes at 60 Gy. Positron emission tomography (PET)-computed tomography (CT) examination 3 months after the radiotherapy identified accumulation of fluorodeoxyglucose (FDG) in a supraclavicular lymph node and the thoracic wall; hence, a chemotherapeutic regimen with eribulin was initiated. At 11 months after initiation of eribulin, complete response was achieved, indicated by the absence of FDG accumulation in both the supraclavicular lymph node and the thoracic wall on PET-CT. The treatment efficacy of eribulin is considered to be a result of the mixed morphology of squamous cell carcinoma, including the presence of an epithelial component, such as adenocarcinoma cells, and a mesenchymal component, in the form of sarcomatoid cells. Eribulin displayed an effect similar to that of adriamycin against malignant soft tissue tumors and was shown to effectively target mesenchymal components. In cases of reduced expression of the DNA repair pathway components, such as in metaplastic carcinomas, eribulin may be more effective compared with adriamycin, the mechanism of action of which involves inhibition of DNA synthesis. A superior therapeutic effect was obtained with eribulin in squamous cell carcinoma. Therefore, eribulin appears to be a promising, effective therapeutic choice for the management of metaplastic carcinomas, including squamous cell carcinomas.}, } @article {pmid30154546, year = {2018}, author = {Tomko, LA and Hill, RC and Barrett, A and Szulczewski, JM and Conklin, MW and Eliceiri, KW and Keely, PJ and Hansen, KC and Ponik, SM}, title = {Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12941}, pmid = {30154546}, issn = {2045-2322}, support = {R01 CA179556/CA/NCI NIH HHS/United States ; T32 GM008688/GM/NIGMS NIH HHS/United States ; R33 CA183685/CA/NCI NIH HHS/United States ; CA206458//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; R01 CA206458/CA/NCI NIH HHS/United States ; T32 HL007171/HL/NHLBI NIH HHS/United States ; R01 CA199996/CA/NCI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 CA142833/CA/NCI NIH HHS/United States ; S10 OD021641/OD/NIH HHS/United States ; R01 CA186134/CA/NCI NIH HHS/United States ; DK104310//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; CA199996//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; CA185251//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; CA186134//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; CA179556//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/International ; R01 CA185251/CA/NCI NIH HHS/United States ; U54 DK104310/DK/NIDDK NIH HHS/United States ; }, mesh = {Breast/chemistry ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Collagen/*analysis ; Extracellular Matrix/*chemistry/ultrastructure ; Extracellular Matrix Proteins/*analysis ; Female ; Humans ; Neoplasm Proteins/*analysis ; Proteomics ; Stromal Cells/*chemistry ; Tenascin/*analysis ; Thrombospondins/*analysis ; *Tumor Microenvironment ; }, abstract = {Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (TACS). Late stages of this progression are characterized by the presence of bundled, straight collagen (TACS-2) that become oriented perpendicular to the tumor-stromal boundary (TACS-3). Importantly, the presence of TACS-3 collagen is an independent predictor of poor patient outcome. At present, it remains unclear whether reorganization of the collagen matrix is the consequence of mechanical or compositional tissue remodeling. Here, we identify compositional changes in ECM correlating to collagen fiber reorganization from nineteen normal and invasive ductal carcinoma (IDC) patient biopsies using matrisome-targeted proteomics. Twenty-seven ECM proteins were significantly altered in IDC samples compared to normal tissue. Further, a set of nineteen matrisome proteins positively correlate and five proteins inversely correlate with IDC tissues containing straightened collagen fibers. Tenascin-C and thrombospondin-2 significantly co-localized with aligned collagen fibers in IDC tissues. This study highlights the compositional change in matrisome proteins accompanying collagen re-organization during breast cancer progression and provides candidate proteins for investigation into cellular and structural influences on collagen alignment.}, } @article {pmid30151336, year = {2018}, author = {Miše, I and Vučić, M}, title = {Comparison of Syndecan-1 Immunohistochemical Expression in Lobular and Ductal Breast Carcinoma with Nodal Metastases.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {2018}, number = {}, pages = {9432375}, pmid = {30151336}, issn = {2210-7185}, mesh = {Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Carcinoma, Lobular/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Syndecan-1/*metabolism ; }, abstract = {Syndecan-1 (Sdc1) is a transmembrane heparan sulfate proteoglycan, an extracellular matrix receptor involved in intercellular communication, proliferation, angiogenesis, and metastasis. This study determined and compared Sdc1 expression in the tumor cells and stroma of 30 invasive lobular and 30 invasive ductal breast carcinomas (ILCs/IDCs), also in the axillary node metastases of ductal type, and correlated it with clinical and tumor parameters. Sdc1 was expressed in the epithelium of 90% carcinoma of both histological types. Also, it was most frequently expressed in their tumor stroma, but in ILC, stromal expression was negative in 40%. Sdc1 was expressed in 86.7% of the metastatic epithelium of IDC nodal metastases (in even 50% as high expression), while the nodal stroma was negative in 46.7%. Primary IDC showed a negative correlation between epithelial Sdc1 and progesterone receptors (PRs), whereas ILC showed a positive correlation between stromal Sdc1 and histological gradus. In the metastatic epithelium, Sdc1 was negatively correlated with a patient's age, estrogen receptors (ERs), and PRs in the primary tumors, while the stroma of metastases demonstrated a positive correlation with the focus number in primary tumors and a negative correlation with PRs in primary tumors. This research revealed identical overall epithelial Sdc1 expression in both breast carcinomas with no statistically significant difference in its stromal expression and confirmed the role of Sdc1 in the progression of both tumor types and in the development of ductal carcinoma's metastatic potential.}, } @article {pmid30150891, year = {2018}, author = {Struk-Panfil, M and Błaut, K and Pęksa, R and Kmieć, P and Sworczak, K}, title = {Liver metastasis of a neuroendocrine neoplasm of unknown primary origin in a female patient with a history of breast cancer.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {22}, number = {2}, pages = {124-128}, pmid = {30150891}, issn = {1428-2526}, abstract = {We report on and discuss a case of a female patient diagnosed with breast cancer in 1996, which was histopathologically assessed as an invasive ductal carcinoma. The patient was admitted to our Department in 2017 with a liver metastasis of a neuroendocrine tumour. On admission she had no symptoms of an endo-crinopathy and was in a good general condition. Due to unknown primary site of the metastasis and given the patient's history of breast cancer, it was suspected that the breast cancer was in fact a neuroendocrine tumour. This hypothesis was confirmed by comparing histopathological specimens of the breast and liver tumours using advanced pathological methods.}, } @article {pmid30150157, year = {2018}, author = {Ahmeidat, H and Purdie, C and Jordan, L and Fleming, D and McCullough, J and Evans, A}, title = {Non-histopathological parameters associated with upgrade of breast tumours yielding a core biopsy report of histological grade 2 ductal no special type to grade 3 on excision.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {44}, number = {11}, pages = {1720-1724}, doi = {10.1016/j.ejso.2018.07.002}, pmid = {30150157}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast Neoplasms/diagnostic imaging/*pathology/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Mammography ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness/pathology ; Prognosis ; Prospective Studies ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: The aim of the study was to identify clinical, radiological and immuno-histochemical factors that may help predict upgrade of invasive ductal cancers of no special type (IDC-NST) with a core biopsy grade of 2 to grade 3 on final histology.

METHODS: A prospectively maintained database of ultrasound visible solid masses was used to identify lesions yielding a core biopsy result of IDC-NST grade 2 who underwent immediate surgery yielding a grade 2 or grade 3 tumour. Associations were sought between the source of patient (screening/symptomatic), core biopsy receptor status and imaging findings and the grade of the excision specimen tumour. Statistical analysis, which included the chi-squared test, ROC curves and Cox regression analysis, was used to compare upgrade vs no upgrade for each factor.

RESULTS: 463 IDC-NST breast cancers of core biopsy grade 2 gave 344 grade 2 and 119 grade 3 tumours at excision. Factors significantly associated with upgrade were large ultrasound (US) size, hyperechogencity, stiffness at shearwave elastography (SWE), calcification on mammography and oestrogen receptor (ER) and progesterone receptor (PR) negativity. Patient source, Human epidermal growth factor receptor 2 (HER-2) status, ultrasound (US) distal effect and mammographic spiculation were not significantly associated with chance of upgrade. On multivariate analysis, only US size maintained statistical significance.

CONCLUSION: Oncologists and surgeons should be aware that lesions with a core biopsy diagnosis of grade 2 IDC-NST measuring over 15 mm on US have a 37% chance of being grade 3 on excision and this should be considered when deciding pre-operative management.}, } @article {pmid30149270, year = {2018}, author = {Yirmiya, K and Djalovski, A and Motsan, S and Zagoory-Sharon, O and Feldman, R}, title = {Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth.}, journal = {Psychoneuroendocrinology}, volume = {98}, number = {}, pages = {153-160}, doi = {10.1016/j.psyneuen.2018.08.016}, pmid = {30149270}, issn = {1873-3360}, mesh = {Adolescent ; Adult ; Adverse Childhood Experiences ; Anxiety/*etiology/metabolism/psychology ; Biomarkers/blood ; Child ; Female ; Humans ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System ; Immunity, Innate/physiology ; Immunoglobulin A, Secretory ; Male ; Mother-Child Relations/*psychology ; Mothers ; Parenting/*psychology ; Pituitary-Adrenal System ; Saliva/chemistry ; Social Behavior ; Stress Disorders, Post-Traumatic/metabolism ; Stress, Psychological/metabolism ; }, abstract = {The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.}, } @article {pmid30144784, year = {2018}, author = {Shah, S and Brock, EJ and Jackson, RM and Ji, K and Boerner, JL and Sloane, BF and Mattingly, RR}, title = {Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.}, journal = {Neoplasia (New York, N.Y.)}, volume = {20}, number = {9}, pages = {951-963}, pmid = {30144784}, issn = {1476-5586}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R25 GM058905/GM/NIGMS NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; R21 CA175931/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Line, Tumor ; Cytoskeleton/metabolism ; Down-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA Interference ; }, abstract = {Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and reversed the mesenchymal phenotype. Similarly, introduction of dominant negative Rap1A mutant (Rap1A-N17) in DCIS-Rap1Gap shRNA cells caused a reversion to nonmalignant phenotype. Conversely, expression of constitutively active Rap1A mutant (Rap1A-V12) in noninvasive MCF10.DCIS cells led to phenotypic changes that were reminiscent of Rap1Gap knockdown. Thus, reduction of Rap1Gap in DCIS is a potential switch for progression to an invasive phenotype. The Graphical Abstract summarizes these findings.}, } @article {pmid30142303, year = {2020}, author = {Meyer, GJ and Hosseininasab, A and Viglione, DJ and Mihura, JL and Berant, E and Resende, AC and Reese, J}, title = {The Effect of CS Administration or an R-Optimized Alternative on Potential Projective Material in Rorschach Responses From Six Studies and a Meta-Analysis of Their Findings.}, journal = {Journal of personality assessment}, volume = {102}, number = {1}, pages = {135-146}, doi = {10.1080/00223891.2018.1492926}, pmid = {30142303}, issn = {1532-7752}, mesh = {Adult ; Female ; Humans ; Male ; Psychometrics/*standards ; Rorschach Test/*standards ; }, abstract = {The Rorschach Performance Assessment System (R-PAS; Meyer, Viglione, Mihura, Erard, & Erdberg, 2011) introduced R-optimized administration to reduce variability in the number of Responses (R). We provide new data from six studies of participants randomly assigned to receive a version of this method or Comprehensive System (CS; Exner, 2003) administration. We examine how administration methods affect 3 types of codes most likely to contain potential projective material and the frequency of these codes for the 1st, 2nd, 3rd, 4th, or last response to a card (R in Card). In a meta-analytic summary, we found 37% of responses have 1 type of code, 19% have 2 types, and 3% have all 3 types, with stable proportions across responses within cards. Importantly, administration method had no impact on potential projective variable means. Differential skew across samples made variability harder to interpret. Initial results suggesting differences in 3 of the 18 specific Type by R in Card pairs did not follow a coherent pattern and disappeared when using raw counts from all participants. Overall, data do not support concerns that R-optimized administration might alter potential projective processes, or make potentially "signature" last responses to the card any different in R-PAS than the CS.}, } @article {pmid30135203, year = {2018}, author = {Ali Khan, A and Hansson, J and Weber, P and Foehr, S and Krijgsveld, J and Herzig, S and Scheideler, M}, title = {Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines.}, journal = {Molecular & cellular proteomics : MCP}, volume = {17}, number = {12}, pages = {2358-2370}, pmid = {30135203}, issn = {1535-9484}, mesh = {Adipocytes, Brown/*metabolism ; Adipocytes, White/*metabolism ; Adipokines/*analysis/biosynthesis ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Carbohydrate Metabolism ; Cell Death ; Cells, Cultured ; Chromatography, Liquid ; Leptin/analysis ; Linear Models ; Male ; Mice ; Mice, Inbred C57BL ; Norepinephrine/pharmacology ; Oxidation-Reduction ; Resistin/analysis ; Secretory Pathway/*physiology ; Tandem Mass Spectrometry ; }, abstract = {The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands. Recent studies have demonstrated that white and brown adipocytes also function as endocrine cells and regulate systemic metabolism by secreting factors that act locally and systemically. However, a comparative proteomic analysis of secreted factors from white and brown adipocytes and their responsiveness to adrenergic stimulation has not been reported yet. Therefore, we studied and compared the secretome of white and brown adipocytes, with and without norepinephrine (NE) stimulation. Our results reveal that carbohydrate-metabolism-regulating proteins are preferably secreted from white adipocytes, while brown adipocytes predominantly secrete a large variety of proteins. Upon NE stimulation, an increased secretion of known adipokines is favored by white adipocytes while brown adipocytes secreted higher amounts of novel adipokines. Furthermore, the secretory response between NE-stimulated and basal state was multifaceted addressing lipid and glucose metabolism, adipogenesis, and antioxidative reactions. Intriguingly, NE stimulation drastically changed the secretome in brown adipocytes. In conclusion, our study provides a comprehensive catalogue of novel adipokine candidates secreted from white and brown adipocytes with many of them responsive to NE. Given the beneficial effects of brown adipose tissue activation on its endocrine function and systemic metabolism, this study provides an archive of novel batokine candidates and biomarkers for activated brown adipose tissue.}, } @article {pmid30129904, year = {2018}, author = {García-Tejedor, A and Guma, A and Soler, T and Valdivieso, A and Petit, A and Contreras, N and Chappuis, CG and Falo, C and Pernas, S and Amselem, A and Plà, MJ and Fernández-Montolí, E and Burdío, F and Ponce, J}, title = {Radiofrequency Ablation Followed by Surgical Excision versus Lumpectomy for Early Stage Breast Cancer: A Randomized Phase II Clinical Trial.}, journal = {Radiology}, volume = {289}, number = {2}, pages = {317-324}, doi = {10.1148/radiol.2018180235}, pmid = {30129904}, issn = {1527-1315}, mesh = {Aged ; Aged, 80 and over ; Breast/diagnostic imaging/surgery ; Breast Neoplasms/diagnostic imaging/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Prospective Studies ; Radiofrequency Ablation/*methods ; Treatment Outcome ; Ultrasonography, Interventional ; }, abstract = {Purpose To compare the safety and efficacy of US-guided percutaneous radiofrequency ablation (RFA) as a local treatment for breast cancer with that of lumpectomy. Materials and Methods A prospective, randomized open-label phase II clinical trial (clinicaltrials.gov identification number NCT02281812) was conducted in a single institution from 2013 to 2017. Women with invasive ductal carcinoma of the breast measuring 2 cm or smaller were randomly assigned to receive RFA or lumpectomy alone (control group). Margin status at surgery, tumor cell viability after RFA (with nicotinamide adenine dinucleotide [NADH] and cytokeratin 18 [CK18] staining), cosmetic results, adverse events, and local recurrences were evaluated with univariable and multivariable analyses. Results Forty subjects (20 in the RFA group and 20 in the lumpectomy group) were evaluated. The mean participant age was 64 years (range, 46-86 years). NADH and CK18 staining demonstrated absence of tumor cell viability after RFA with at least one of the two techniques. The surgical margins were positive in 11 of the 20 participants in the lumpectomy group (55%) and four of the 20 in the RFA group (20%) (P = .02). Median follow-up was 25 months (range, 1-83 months). Local breast inflammation after surgery was higher in the RFA group than in the lumpectomy group (40% [eight of 20 participants] vs 5% [one of 20 participants], respectively; P = .01). Local infection occurred in three participants who underwent RFA (two of whom had undergone partial irradiation of the breast). None of the participants in the control group developed local infection. No participants had recurrence or the need for a second surgery during the study period. Conclusion This preliminary study showed that radiofrequency ablation was effective for local tumor control and that tumor-free margins were obtained more often with radiofrequency ablation than with lumpectomy. Surgical excision after radiofrequency ablation was infrequently associated with local infection. © RSNA, 2018 Online supplemental material is available for this article.}, } @article {pmid30129697, year = {2019}, author = {Ha, R and Chang, P and Mutasa, S and Karcich, J and Goodman, S and Blum, E and Kalinsky, K and Liu, MZ and Jambawalikar, S}, title = {Convolutional Neural Network Using a Breast MRI Tumor Dataset Can Predict Oncotype Dx Recurrence Score.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {49}, number = {2}, pages = {518-524}, pmid = {30129697}, issn = {1522-2586}, support = {R38 CA231577/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Algorithms ; Area Under Curve ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Imaging, Three-Dimensional ; *Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Recurrence, Local ; *Neural Networks, Computer ; ROC Curve ; Receptor, ErbB-2/metabolism ; Reproducibility of Results ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Oncotype Dx is a validated genetic analysis that provides a recurrence score (RS) to quantitatively predict outcomes in patients who meet the criteria of estrogen receptor positive / human epidermal growth factor receptor-2 negative (ER+/HER2-)/node negative invasive breast carcinoma. Although effective, the test is invasive and expensive, which has motivated this investigation to determine the potential role of radiomics.

HYPOTHESIS: We hypothesized that convolutional neural network (CNN) can be used to predict Oncotype Dx RS using an MRI dataset.

STUDY TYPE: Institutional Review Board (IRB)-approved retrospective study from January 2010 to June 2016.

POPULATION: In all, 134 patients with ER+/HER2- invasive ductal carcinoma who underwent both breast MRI and Oncotype Dx RS evaluation. Patients were classified into three groups: low risk (group 1, RS <18), intermediate risk (group 2, RS 18-30), and high risk (group 3, RS >30).

FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T. Breast MRI, T1 postcontrast.

ASSESSMENT: Each breast tumor underwent 3D segmentation. In all, 1649 volumetric slices in 134 tumors (mean 12.3 slices/tumor) were evaluated. A CNN consisted of four convolutional layers and max-pooling layers. Dropout at 50% was applied to the second to last fully connected layer to prevent overfitting. Three-class prediction (group 1 vs. group 2 vs. group 3) and two-class prediction (group 1 vs. group 2/3) models were performed.

STATISTICAL TESTS: A 5-fold crossvalidation test was performed using 80% training and 20% testing. Diagnostic accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) area under the curve (AUC) were evaluated.

RESULTS: The CNN achieved an overall accuracy of 81% (95% confidence interval [CI] ± 4%) in three-class prediction with specificity 90% (95% CI ± 5%), sensitivity 60% (95% CI ± 6%), and the area under the ROC curve was 0.92 (SD, 0.01). The CNN achieved an overall accuracy of 84% (95% CI ± 5%) in two-class prediction with specificity 81% (95% CI ± 4%), sensitivity 87% (95% CI ± 5%), and the area under the ROC curve was 0.92 (SD, 0.01).

DATA CONCLUSION: It is feasible for current deep CNN architecture to be trained to predict Oncotype DX RS.

LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:518-524.}, } @article {pmid30124442, year = {2018}, author = {Clement, Z and McLeay, W and Hoffmann, C and Shin, P and Kiu, A and Eaton, M}, title = {Role of radiotherapy in women over the age of 65 after breast conserving surgery for breast cancer: A 5-year retrospective study.}, journal = {Breast disease}, volume = {37}, number = {4}, pages = {197-205}, doi = {10.3233/BD-180340}, pmid = {30124442}, issn = {1558-1551}, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Female ; Humans ; Mammography ; Mastectomy, Segmental/*statistics & numerical data ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND/OBJECTIVE: This study aimed to analyse the local recurrence (LR) and breast cancer related mortality (BCRM) in older women who underwent breast-conserving surgery (BCS) with and without adjuvant radiotherapy (XRT).

METHODS: This retrospective study included a total of 299 women who underwent BCS for early breast carcinoma, between the years of 2007 and 2011. Predictive risk factors, local recurrence (LR) and breast cancer related mortality (BCRM) were assessed with a mean follow-up period of 84 months.

RESULTS: Women over the age of 65 in the XRT and No-XRT groups showed similar incidence of LR (5.8% vs 5%, p = 0.838). Women over 65 years old with XRT had a higher rate of BCRM (5.8% vs 0%, p = 0.05). Resection margins >5 mm had a lower rate of BCRM (HR 0.395, p = 0.05). Women under the age of 65, invasive ductal carcinoma, grade-3 tumours, HER-2 positive, triple negative, lympho-vascular invasion, axillary lymph node positivity, high breast density on mammography were associated with increased risk of LR and BCRM.

CONCLUSIONS: XRT in women over the age of 65 did not decrease the risk of LR. Adjuvant XRT in older women should be offered to selective patients with high risk patient and tumour factors.}, } @article {pmid30122991, year = {2018}, author = {Zhao, Y and Song, K and Zhang, Y and Xu, H and Zhang, X and Wang, L and Fan, C and Jiang, G and Wang, E}, title = {TMEM17 promotes malignant progression of breast cancer via AKT/GSK3β signaling.}, journal = {Cancer management and research}, volume = {10}, number = {}, pages = {2419-2428}, pmid = {30122991}, issn = {1179-1322}, abstract = {PURPOSE: Current knowledge of TMEM17, a recently identified protein of the transmembrane (TMEM) family, is limited, especially with respect to its expression and biological functions in malignant tumors. This study analyzed TMEM17 expression in invasive breast cancer tissue and breast cell lines and its relevance to clinicopathological factors, and investigated the mechanisms underlying the biological effects of TMEM17 on breast cancer cells.

PATIENTS AND METHODS: TMEM17 protein expression was determined in 20 freshly harvested specimens (tumor and paired normal tissues) by Western blotting. Immunohistochemical analysis was performed to determine the expression and subcellular localization of TMEM17 in samples from 167 patients (mean age, 49 years) diagnosed with invasive ductal carcinoma (38 with triple-negative breast cancer; 129 with non-triple-negative breast cancer) who underwent complete resection in the First Affiliated Hospital of China Medical University between 2011 and 2013. Furthermore, TMEM17 was knocked down by small interfering RNAs in breast cancer cell lines.

RESULTS: TMEM17 was found to be significantly upregulated in breast cancer tissues compared to the corresponding normal breast tissues by Western blotting (p=0.015). Immunohistochemical analysis revealed that TMEM was significantly upregulated in invasive breast cancer cells compared to adjacent normal breast duct glandular epithelial cells (10.78% vs 76.05%, p<0.001), and its expression was closely related to the patient's T-stage (p=0.022), advanced TNM stages (p=0.007), and lymph node metastasis (p=0.012). After TMEM17 knockdown or overexpression in breast cancer cell lines, TMEM17 upregulated p-AKT, p-GSK3β, active β-catenin, and Snail, and downstream target proteins c-myc and cyclin D1, and downregulated E-cadherin, resulting in increased cancer cell proliferation, invasion, and migration. These effects were reversed by the AKT inhibitor LY294002.

CONCLUSION: Our results indicate that TMEM17 is upregulated in breast cancer tissues and can promote malignant progression of breast cancer cells by activating the AKT/GSK3β signaling pathway.}, } @article {pmid30119158, year = {2018}, author = {Köremezli Keskin, N and Balcı, P and Başara Akın, I and Yavuz Gürkan, E and Sevinç, Aİ and Durak, MG and Erşen Danyeli, A}, title = {Detection of the differences in the apparent diffusion coefficient values in different histopathological types of malignant breast lesions and comparison of cellular region/ stroma ratio and histopathological results.}, journal = {Turkish journal of medical sciences}, volume = {48}, number = {4}, pages = {817-825}, doi = {10.3906/sag-1801-89}, pmid = {30119158}, issn = {1303-6165}, mesh = {Adult ; Aged ; Biopsy ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Lobular/*diagnosis ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/methods ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Middle Aged ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND/AIM: This study aimed to compare the apparent diffusion coefficient (ADC) values of malignant breast lesions with different histopathological types on diffusion-weighted imaging (DWI) and the cellular region/stroma (CR/S) ratio and histopathological results.

MATERIALS AND METHODS: Breast diffusion-weighted magnetic resonance findings of 59 patients were retrospectively analyzed for malignant breast lesions. The CR/S ratio was calculated using breast wide-excisional biopsy or mastectomy specimens.

RESULTS: Receiver operating characteristic analysis was performed for malignant lesions and subtypes. An ADC threshold of 1.260 × 10 –3 mm 2 /s was set to detect invasive ductal carcinoma with 80.8% sensitivity and 81.4% specificity. An ADC threshold of 1.391 × 10 –3 mm 2 /s was set to detect invasive lobular carcinoma lesions with 88.2% sensitivity and 79.5% specificity. The ADC value for lesions with low CR/S ratio (n = 21) was 1.135 ± 0.429 × 10 –3 mm 2 /s and it was 1.155 ± 0.429 × 10 –3 mm 2 /s in the high CR/S ratio group (n = 18).

CONCLUSION: ADC value calculation does not seem to be used as an alternative for histopathological detection, which is the gold standard for the differentiation of subtypes of malignant breast cancer. In addition, since there is a positive correlation between CR/S ratio and ADC values, it may be a strong marker to evaluate the stromal component of lesions.}, } @article {pmid30118160, year = {2019}, author = {Hirschfeld-Dicker, L and Samuel, RD and Tiram Vakrat, E and Dubnov-Raz, G}, title = {Preferred weight-related terminology by parents of children with obesity.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {108}, number = {4}, pages = {712-717}, doi = {10.1111/apa.14538}, pmid = {30118160}, issn = {1651-2227}, mesh = {Adolescent ; Adult ; Aged ; *Attitude to Health ; *Body Weight ; Child ; Consumer Behavior ; Female ; Humans ; Male ; Middle Aged ; Motivation ; Parents/*psychology ; *Pediatric Obesity ; *Terminology as Topic ; Young Adult ; }, abstract = {AIM: In order to improve weight-related discussion with patients and minimise their discomfort, the terminology used by medical staff should be carefully chosen. The aim of the study was to identify the most motivating weight-related terminology to use with children with obesity.

METHODS: Focus groups were used to generate a list of 12 weight-related terms in Hebrew, sent by a questionnaire to parents of children and adolescents with obesity. Terms were graded according to how desirable, stigmatising, blaming or motivating they were perceived. We identified the most positive and negative weight-based terms and conducted linear regressions to predict child motivation to lose weight when positive terms are used.

RESULTS: The least stigmatising and most motivating and desirable terms were 'unhealthy body weight' and 'unhealthy lifestyle'. Medical staff mostly used 'overweight', which was relatively inoffensive yet not very motivating. 'Fat/obese' ('Shamen') was the most stigmatising and blaming term and the least desired. Only 20% of parents endorsed a nonverbal graphical tool to describe body size.

CONCLUSION: Our findings encourage using health-based terminology over weight-based terminology to promote treatment and lifestyle changes in children with obesity. Healthcare professionals should adopt patient-centred care and improve the weight-related terms they use with children with obesity.}, } @article {pmid30116958, year = {2019}, author = {Suo, S and Zhang, D and Cheng, F and Cao, M and Hua, J and Lu, J and Xu, J}, title = {Added value of mean and entropy of apparent diffusion coefficient values for evaluating histologic phenotypes of invasive ductal breast cancer with MR imaging.}, journal = {European radiology}, volume = {29}, number = {3}, pages = {1425-1434}, pmid = {30116958}, issn = {1432-1084}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diffusion Magnetic Resonance Imaging/*methods ; Entropy ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Phenotype ; }, abstract = {OBJECTIVES: To study the added value of mean and entropy of apparent diffusion coefficient (ADC) values at standard (800 s/mm[2]) and high (1500 s/mm[2]) b-values obtained with diffusion-weighted imaging in identifying histologic phenotypes of invasive ductal breast cancer (IDC) with MR imaging.

METHODS: One hundred thirty-four IDC patients underwent diffusion-weighted imaging with b-values of 800 and 1500 s/mm[2], and corresponding ADC800 and ADC1500 maps were generated. Mean and entropy of volumetric ADC values were compared with molecular markers (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki-67). Associations among morphologic features, ADC metrics, and phenotypes (luminal A, luminal B [HER2 negative], luminal B [HER2 positive], HER2 positive, and triple negative) were evaluated.

RESULTS: Mean ADC values were significantly decreased in ER-positive, PR-positive, and HER2-negative tumors (p < 0.01). Ki-67 ≥ 20% tumors demonstrated significantly higher ADC entropy values compared with Ki-67 < 20% tumors (p < 0.001). Luminal A subtype tended to display lower ADC entropy values compared with other subtypes, while HER2-positive subtype tended to display higher mean ADC values. ADC1500 entropy provided superior diagnostic performance over ADC800 entropy (p = 0.04). Independent risk factors were ADC1500 entropy (p = 0.002) associated with luminal A, irregular mass shape (p = 0.018) and ADC1500 entropy (p = 0.022) with luminal B (HER2 positive), mean ADC1500 (p = 0.018) with HER2 positive, and smooth mass margin (p = 0.012) and rim enhancement (p = 0.003) with triple negative.

CONCLUSIONS: Mean and entropy of ADC values provided complementary information and added value for evaluating IDC histologic phenotypes. High-b-value ADC1500 may facilitate better phenotype discrimination.

KEY POINTS: • ADC metrics are associated with molecular marker status in IDC. • ADC 1500 improves differentiation of histologic phenotypes compared with ADC 800 . • ADC metrics add value to morphologic features in IDC phenotyping.}, } @article {pmid30110913, year = {2018}, author = {Liu, S and Cruz, ID and Ramos, CC and Taleon, P and Ramasamy, R and Shah, J}, title = {Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for Laboratory Diagnosis of Lyme Disease.}, journal = {Healthcare (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {30110913}, issn = {2227-9032}, abstract = {Accurate laboratory diagnosis of Lyme disease (Lyme borreliosis), caused by the spirochete Borrelia burgdorferi (BB), is difficult and yet important to prevent serious disease. The US Centers for Disease Control and Prevention (CDC) presently recommends a screening test for serum antibodies followed by confirmation with a more specific Western blot (WB) test to detect IgG and IgM antibodies against antigens in whole cell lysates of BB. Borrelia species related to BB cause tick-borne relapsing fever (TBRF). TBRF is increasingly recognized as a health problem in the US and occurs in areas where Lyme disease is prevalent. The two groups of Borrelia share related antigens. We have developed a modified WB procedure termed the Lyme immunoblots (IBs) using recombinant antigens from common strains and species of the BB sensu lato complex for serological diagnosis of Lyme disease. A reference collection of 178 sera from 26 with and 152 patients without Lyme disease were assessed by WB and IB in a blinded manner using either criteria for positive antibody reactions recommended by the CDC or criteria developed in-house. The sensitivity, specificity, positive and negative predictive values obtained with the reference sera suggest that the Lyme IB is superior to the Lyme WB for detection of specific antibodies in Lyme disease. The Lyme IB showed no significant reaction with rabbit antisera produced against two Borrelia species causing TBRF in the US, suggesting that the Lyme IB may be also useful for excluding TBRF.}, } @article {pmid30110018, year = {2018}, author = {Yildirim, N and Bahceci, A}, title = {Use of pertuzumab and trastuzumab during pregnancy.}, journal = {Anti-cancer drugs}, volume = {29}, number = {8}, pages = {810-813}, doi = {10.1097/CAD.0000000000000658}, pmid = {30110018}, issn = {1473-5741}, mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy ; Docetaxel/administration & dosage/adverse effects ; Female ; Fetus/*drug effects ; Humans ; Oligohydramnios/*chemically induced ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy ; Trastuzumab/administration & dosage/adverse effects ; Young Adult ; }, abstract = {Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy.}, } @article {pmid30101014, year = {2018}, author = {Yan, L and Dong, X and Xu, H and Huang, J and Wang, W and Huang, L and Wan, Q and Gong, J}, title = {Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {2}, pages = {163-167}, pmid = {30101014}, issn = {2049-9450}, abstract = {Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication of cancer characterized by rapid development of cerebellar ataxia. We herein present a case of a 67-year-old female patient with PCD caused by breast cancer. The patient presented with progressively worsening cerebellar deficits that had been misdiagnosed for several months prior to the identification of the anti-Yo autoantibodies in the serum. A whole-body positron emission tomography/computed tomography scan revealed a lesion in the lower outer quadrant of the left breast with slightly increased metabolism. On mammography, a lobulated high-density mass was identified in the left breast. The patient underwent left breast lumpectomy and the histological examination confirmed the presence of an invasive ductal carcinoma. After breast surgery, the patient exhibited marked neurological improvement at the 12-month follow-up. Therefore, it is crucial that clinicians include paraneoplastic neurological syndromes in the differential diagnosis of neurological disorders. The detection of characterized onconeural antibodies in the serum or cerebrospinal fluid may provide guidance in the search for an underlying tumor.}, } @article {pmid30098440, year = {2018}, author = {Martín-Saavedra, F and Escudero-Duch, C and Prieto, M and Sánchez-Casanova, S and López, D and Arruebo, M and Voellmy, R and Santamaría, J and Vilaboa, N}, title = {Pro-angiogenic near infrared-responsive hydrogels for deliberate transgene expression.}, journal = {Acta biomaterialia}, volume = {78}, number = {}, pages = {123-136}, doi = {10.1016/j.actbio.2018.08.006}, pmid = {30098440}, issn = {1878-7568}, mesh = {Animals ; Biocompatible Materials/*pharmacology ; Copper/chemistry ; Fibrinolysis/drug effects ; *Gene Expression ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Hydrogels/*pharmacology ; Mice ; NIH 3T3 Cells ; Nanoparticles/chemistry/ultrastructure ; *Neovascularization, Physiologic/drug effects ; Proteolysis/drug effects ; *Spectroscopy, Near-Infrared ; Sulfides/chemistry ; Transgenes ; }, abstract = {UNLABELLED: CuS nanoparticles (CuSNP) are degradable, readily prepared, inexpensive to produce and efficiently cleared from the body. In this work, we explored the feasibility of CuSNP to function as degradable near infrared (NIR) nanotransducers within fibrin-based cellular scaffolds. To prepare NIR-responsive CuSNP hydrogels, fibrinogen was dissolved in cell culture medium and supplemented with aqueous dispersions of CuSNP. Fibrinogen polymerization was catalyzed by the addition of thrombin. In some experiments, HUVEC, C3H/10T1/2 or C3H/10T1/2-fLuc cells, that harbor a heat-activated and rapamycin-dependent gene switch for regulating the expression of firefly luciferase transgene, were incorporated to the sol phase of the hydrogel. For in vivo experiments, hydrogels were injected subcutaneously in the back of adult C3H/HeN mice. Upon NIR irradiation, CuSNP hydrogels allowed heat-inducible and rapamycin-dependent transgene expression in cells contained therein, in vitro and in vivo. C3H/10T1/2 cells cultured in CuSNP hydrogels increased metabolic activity, survival rate and fibrinolytic activity, which correlated with changes at the transcriptome level. Media conditioned by CuSNP hydrogels increased viability of HUVEC which formed pseudocapillary structures and remodeled protein matrix when entrapped within these hydrogels. After long-term implantation, the skin patches that covered the CuSNP hydrogels showed increased capillary density which was not detected in mice implanted with matrices lacking CuSNP. In summary, NIR-responsive scaffolds harboring CuSNP offer compelling features in the tissue engineering field, as degradable implants with enhanced integration capacity in host tissues that can provide remote controlled deployment of therapeutic gene products.

STATEMENT OF SIGNIFICANCE: Hydrogels composed of fibrin embedding copper sulfide nanoparticles (CuSNP) efficiently convert incident near infrared (NIR) energy into heat and can function as cellular scaffolding. NIR laser irradiation of CuSNP hydrogels can be employed to remotely induce spatiotemporal patterns of transgene expression in genetically engineered multipotent stem cells. CuSNP incorporation in hydrogel architecture accelerates the cell-mediated degradation of the fibrin matrix and induces pro-angiogenic responses that may facilitate the integration of these NIR-responsive scaffolds in host tissues. CuSNP hydrogels that harbor cells capable of controlled expression of therapeutic gene products may be well suited for tissue engineering as they are biodegradable, enhance implant vascularization and can be used to deploy growth factors in a desired spatiotemporal fashion.}, } @article {pmid30098295, year = {2018}, author = {Ohashi, R and Namimatsu, S and Sakatani, T and Naito, Z and Takei, H and Shimizu, A}, title = {Prognostic utility of atypical mitoses in patients with breast cancer: A comparative study with Ki67 and phosphohistone H3.}, journal = {Journal of surgical oncology}, volume = {118}, number = {3}, pages = {557-567}, doi = {10.1002/jso.25152}, pmid = {30098295}, issn = {1096-9098}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Histones/*metabolism ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; *Mitosis ; *Mitotic Index ; Phosphorylation ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the presence of atypical mitoses is associated with poor prognosis in some types of cancer, but its clinical significance remains uncertain. Here, we investigated the occurrence of atypical mitoses in breast cancers.

METHODS: Mitotic figures, including normal and atypical mitoses, were assessed in resected histological sections from 109 patients with invasive carcinoma of no special type (ICNST). Comparisons with clinicopathological features and biomarkers such as Ki67 and phosphohistone H3 (PHH3) were performed.

RESULTS: The total number of mitotic figures, including atypical mitoses, was higher in situ and invasive ductal carcinoma components than in normal ducts. Morphological characteristics of atypical mitoses included multipolar, lagged, ring, asymmetrical mitoses, and anaphase bridge. Patients with higher total mitoses and PHH3, and the presence of atypical mitoses showed reduced overall survival (OS), compared to those with lower total mitoses and PHH3, and without atypical mitoses (P = 0.03, 0.02, and <0.001, respectively). In multivariate analysis, the presence of atypical mitoses alone attained significant correlation with shorter OS (P < 0.001).

CONCLUSIONS: Atypical mitoses in routinely resected specimens have a robust prognostic value for ICNST of the breast, but its clinical utility remains to be validated in a multicenter large material.}, } @article {pmid30096623, year = {2018}, author = {Lahav-Kadmiel, Z and Brunstein-Klomek, A}, title = {Bullying victimization and depressive symptoms in adolescence: The moderating role of parent-child conflicts among boys and girls.}, journal = {Journal of adolescence}, volume = {68}, number = {}, pages = {152-158}, doi = {10.1016/j.adolescence.2018.07.014}, pmid = {30096623}, issn = {1095-9254}, mesh = {Adolescent ; Bullying/*psychology ; Child ; Crime Victims/*psychology ; Depression/*etiology ; Family Conflict/*psychology ; Female ; Humans ; Israel ; Male ; *Parent-Child Relations ; Self Report ; Sex Factors ; }, abstract = {INTRODUCTION: The association between bullying victimization and depressive symptoms has been studied extensively over the years. Among the variables studied as having an impact on this association were different characteristics of the parent-child relationship. The current study was the first to specifically examine parent-child conflicts as a moderator in the association between victimization and depressive symptoms among adolescents. In addition, it was the first to examine the roles of the child and parent's gender in this moderation.

METHODS: 505 7th-9th graders from two schools in two different cities across Israel (mean age = 12.736, SD = 0.8154) participated in this study. 223 (44.2%) of the participants were male. The participants filled out a battery of self-report questionnaires assessing the different study's variables.

RESULTS: Significant gender differences were found: among girls, the association between bullying victimization and depressive symptoms was stronger when the level of parent-child conflicts was high, while among boys, it was stronger when the level of conflicts was low.

CONCLUSIONS: Our results indicate that the psychological outcomes for victims depend on their relationship with their parents. Bullying intervention programs should include the victims' parents. Furthermore, intervention programs should be designed to fit the different needs of girls and boys.}, } @article {pmid30096287, year = {2018}, author = {Ngara, M and Palmkvist, M and Sagasser, S and Hjelmqvist, D and Björklund, ÅK and Wahlgren, M and Ankarklev, J and Sandberg, R}, title = {Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene signature among sexual stage Plasmodium falciparum parasites.}, journal = {Experimental cell research}, volume = {371}, number = {1}, pages = {130-138}, doi = {10.1016/j.yexcr.2018.08.003}, pmid = {30096287}, issn = {1090-2422}, mesh = {Erythrocytes/*parasitology/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Ontology ; Genetic Heterogeneity ; Humans ; Life Cycle Stages/*genetics ; Molecular Sequence Annotation ; Plasmodium falciparum/*genetics/growth & development/metabolism ; Protozoan Proteins/*genetics/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Transcriptome ; }, abstract = {The malaria parasite has a complex lifecycle, including several events of differentiation and stage progression, while actively evading immunity in both its mosquito and human hosts. Important parasite gene expression and regulation during these events remain hidden in rare populations of cells. Here, we combine a capillary-based platform for cell isolation with single-cell RNA-sequencing to transcriptionally profile 165 single infected red blood cells (iRBCs) during the intra-erythrocytic developmental cycle (IDC). Unbiased analyses of single-cell data grouped the cells into eight transcriptional states during IDC. Interestingly, we uncovered a gene signature from the single iRBC analyses that can successfully discriminate between developing asexual and sexual stage parasites at cellular resolution, and we verify five, previously undefined, gametocyte stage specific genes. Moreover, we show the capacity of detecting expressed genes from the variable gene families in single parasites, despite the sparse nature of data. In total, the single parasite transcriptomics holds promise for molecular dissection of rare parasite phenotypes throughout the malaria lifecycle.}, } @article {pmid30094720, year = {2018}, author = {Hashemi-Sadraei, N and Müller-Greven, GM and Abdul-Karim, FW and Ulasov, I and Downs-Kelly, E and Burgett, ME and Lauko, A and Qadan, MA and Weil, RJ and Ahluwalia, MS and Du, L and Prayson, RA and Chao, ST and Budd, TG and Barnholtz-Sloan, J and Nowacki, AS and Keri, RA and Gladson, CL}, title = {Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.}, journal = {Journal of neuro-oncology}, volume = {140}, number = {2}, pages = {237-248}, pmid = {30094720}, issn = {1573-7373}, support = {R01 CA175120/CA/NCI NIH HHS/United States ; R01-CA152883//National Institutes of Health/ ; R01-CA175120//National Institutes of Health/ ; RPC 2010-1070-R1//Cleveland Clinic Foundation/ ; }, mesh = {Adult ; Aged ; Autophagy-Related Proteins ; Biomarkers, Tumor/metabolism ; Brain/metabolism/pathology ; Brain Neoplasms/*metabolism/mortality/*secondary/therapy ; Breast Neoplasms/metabolism/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology/therapy ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Meta-Analysis as Topic ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Protein-Tyrosine Kinases/*metabolism ; RNA, Messenger/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer.

METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining.

RESULTS: LC3-puncta[+] tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta[+] tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta[+] tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival.

CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.}, } @article {pmid30094546, year = {2018}, author = {Yoo, J and Kim, BS and Yoon, HJ}, title = {Predictive value of primary tumor parameters using [18]F-FDG PET/CT for occult lymph node metastasis in breast cancer with clinically negative axillary lymph node.}, journal = {Annals of nuclear medicine}, volume = {32}, number = {9}, pages = {642-648}, doi = {10.1007/s12149-018-1288-2}, pmid = {30094546}, issn = {1864-6433}, mesh = {Axilla ; Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Predictive Value of Tests ; }, abstract = {OBJECTIVE: This study aimed to demonstrate the clinical significance of total lesion glycolysis (TLG) of primary breast cancer using [18]F-FDG PET/CT to predict axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC) with a clinically negative axillary lymph node (cN-ALN).

METHODS: 135 patients, newly diagnosed with IDC with CN-ALN between July 2016 and October 2017, were retrospectively enrolled. We estimated primary tumor PET/CT parameters including the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and TLG, as well as clinicopathologic findings. All patients received breast surgery followed by pathologic axillary lymph node examination.

RESULTS: Of the 135 patients, 31 (23.0%) were diagnosed with pathologically proven metastatic ALN. In univariate analysis, SUVmax, MTV, and TLG of the primary breast tumor were correlated with metastatic ALN along with tumor size, lymphovascular invasion, CD34, and D2-40. On multivariate analysis, TLG (> 5.74, p = 0.009) had independent significance for predicting ALN metastasis in IDC with cN-ALN.

CONCLUSION: We demonstrated that TLG of primary tumors can be useful in predicting pathologic ALN metastasis in IDC patients with cN-ALN.}, } @article {pmid30094484, year = {2018}, author = {Tadros, AB and Wen, HY and Morrow, M}, title = {Breast Cancers of Special Histologic Subtypes Are Biologically Diverse.}, journal = {Annals of surgical oncology}, volume = {25}, number = {11}, pages = {3158-3164}, pmid = {30094484}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology/surgery ; Carcinoma, Lobular/genetics/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Gene Expression Profiling/*methods ; Genomics ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {BACKGROUND/OBJECTIVE: Cancers classified as "special histologic subtypes" are felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence Score[®] multigene assay to examine prognostic variation within special histologic subtypes. We also examined the Recurrence Score[®] (RS) distribution among the more common ductal (IDC) and lobular (ILC) cancers.

METHODS: 610,350 tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to 8/2017 were included. Specimen histology was classified centrally using a single H&E slide and World Health Organization criteria. RS distribution (low < 18, intermediate 18-30, and high ≥ 31) was compared among histologic subtypes.

RESULTS: Median patient age was 60 years (IQR 51-67); 80% were node negative. Most patients had low RS results (59.2%); only 9.5% had high results. The lowest mean RS was seen in the papillary subtype (11); the highest in the IDC group (18.4). Mean RS for all special subtypes was lower than that of IDC patients. When the high RS threshold was decreased from 31 to 25, as used in the TAILORx and RxPONDER trials, the number of high RS-result patients increased from 9.5% to 16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5 versus 18.4.

CONCLUSION: There is substantial diversity in predicted prognosis among patients with cancers classified as special histologic subtypes, with 12-25% having intermediate RS results and 0.5-9% having high RS results. Pending further definition of the role of chemotherapy for patients with intermediate RS results by TAILORx and RxPONDER, the RS result may help to inform systemic therapy decisions in these patients.}, } @article {pmid30093780, year = {2018}, author = {Arora, S and Sodhi, N and Harith, AK and Kapoor, U}, title = {A case of 'blue skin' and 'dark urine'.}, journal = {Medical journal, Armed Forces India}, volume = {74}, number = {3}, pages = {300-303}, pmid = {30093780}, issn = {0377-1237}, abstract = {A 60-year-old female presented with a 20-year history of progressive dark bluish discoloration of skin and passage of dark colored urine, painful arthritis and a recent history of invasive ductal carcinoma of right breast. Skin biopsy revealed hyaline material which was Periodic-Acid-Schiff stain positive and Congo-red stain negative, urine analysis revealed dark urine with presence reducing substance and radio-imaging showed intervertebral ossification and joint ankyloses. The patient was managed symptomatically with physiotherapy and acetaminophen on as required basis. This image is reported as a classic case of Alkaptonuria with clinical, histopathological and radio-imaging findings and the presence of invasive ductal breast carcinoma in the same patient.}, } @article {pmid30089943, year = {2018}, author = {Sinha, A and Gill, SS}, title = {Correlative Study of Cytological Features in Grading of Invasive Breast Carcinoma.}, journal = {Journal of cytology}, volume = {35}, number = {3}, pages = {149-152}, pmid = {30089943}, issn = {0970-9371}, abstract = {CONTEXT: Fine-needle aspiration cytology (FNAC) is a proven diagnostic technique for establishing the benign or malignant character of breast lesions. Several cytological grading systems have been proposed for grading of carcinoma breast, with results similar to histologic grades.

AIMS: This study sought to evaluate the prognostic value of FNAC in invasive ductal carcinoma of breast by correlating it with histological grade.

SETTINGS AND DESIGN: Tertiary care hospital, retrospective analytical study.

PATIENTS AND METHODS: One hundred and fifty cases of breast carcinoma that underwent modified radical mastectomy consequent to an FNAC diagnosis were included in the study. Robinson's grading system and Elston-Ellis modification of Scarff-Bloom-Richardson grading system were used to assign cytologic and histologic grades, respectively.

STATISTICAL ANALYSIS: The cytological grades were correlated with the histological grades using χ[2]-test and Spearman's rank correlation coefficient. The individual features of the cytological grades were correlated with the histological grades using Kappa coefficient and χ[2]-test. Values were considered significant at P < 0.05.

RESULTS: A statistically significant association was observed between cytologic and histologic grades (r = 0.97; P < 0.01) with sensitivity and specificity, respectively, of 100% and 93.95% for cytological grade 1, 100% and 100% for cytological grade 2 and 100% and 100% for cytological grade 3. Also, a positive correlation was found between each feature of the cytologic grade and the histologic grade (P < 0.05). Among these, a better correlation was demonstrated by cytological features like cell uniformity (Kappa coefficient = 0.50) and appearance of nucleoli (Kappa coefficient = 0.52).

CONCLUSIONS: Robinson's cytologic grading system is a reliable grading method on FNAC smears of cases of carcinoma breast. It correlates well with Elston-Ellis modification of Scarff-Bloom-Richardson grade in invasive ductal carcinoma of breast.}, } @article {pmid30088537, year = {2018}, author = {Delgado-Bocanegra, RE and Millen, EC and Nascimento, CMD and Bruno, KA}, title = {Intraoperative imprint cytology versus histological diagnosis for the detection of sentinel lymph nodes in breast cancer treated with neoadjuvant chemotherapy.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {73}, number = {}, pages = {e363}, pmid = {30088537}, issn = {1980-5322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*drug therapy/*pathology ; Cross-Sectional Studies ; False Negative Reactions ; Female ; Humans ; Immunohistochemistry ; Intraoperative Period ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Grading ; Neoplasm Micrometastasis ; Neoplasm Staging ; Paraffin Embedding/methods ; Reference Values ; Reproducibility of Results ; Sensitivity and Specificity ; Sentinel Lymph Node/*pathology ; Sentinel Lymph Node Biopsy/*methods ; }, abstract = {OBJECTIVES: To compare imprint cytology and paraffin section histology for sentinel lymph node detection in women with breast cancer treated with neoadjuvant chemotherapy.

METHOD: A cross-sectional study and report of the sentinel lymph node statuses of 64 patients with breast cancer who underwent intraoperative imprint cytology and neoadjuvant chemotherapy in a referral cancer institute in Rio de Janeiro, Brazil, between 2014 and 2016.

RESULTS: The mean age was 51 years. The most common histological type was invasive ductal carcinoma (93.75%), and the most common differentiation grade was 2 (62.5%). Overall, 153 lymph nodes were identified, with a mean of 2.39/case. Thirty-four lymph nodes tested positive for malignancy by imprint cytology, and 55 tested positive by histology. Of the 55 positive lymph nodes, 41 (74.5%) involved macrometastases, and 14 (25.5%) involved micrometastases. There were 21 false negatives with imprint cytology, namely, 7 for macrometastases and 14 for micrometastases, resulting in a rate of 17.6%. The sensitivity of imprint cytology was 61.8%, with a specificity and positive predictive value of 100%, a negative predictive value of 82.4% and an accuracy of 86.3%. The method presented null sensitivity for the identification of micrometastases.

CONCLUSIONS: The false-negative rate with imprint cytology was associated with the number of sentinel lymph nodes obtained. The rate found for complete response to neoadjuvant chemotherapy was comparable to the rates reported in the literature. The accuracy of imprint cytology was good, and its specificity was excellent for sentinel lymph node detection; however, the method was unable to detect lymph node micrometastases.}, } @article {pmid30087348, year = {2018}, author = {Senyilmaz-Tiebe, D and Pfaff, DH and Virtue, S and Schwarz, KV and Fleming, T and Altamura, S and Muckenthaler, MU and Okun, JG and Vidal-Puig, A and Nawroth, P and Teleman, AA}, title = {Dietary stearic acid regulates mitochondria in vivo in humans.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3129}, pmid = {30087348}, issn = {2041-1723}, support = {SFB1036//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; RG/12/13/29853/BHF_/British Heart Foundation/United Kingdom ; MC_UU_12012/2/MRC_/Medical Research Council/United Kingdom ; SFB1118//Deutsche Forschungsgemeinschaft (German Research Foundation)/International ; G0802051/MRC_/Medical Research Council/United Kingdom ; 724286//EC | European Research Council (ERC)/International ; MC_UU_00014/5/MRC_/Medical Research Council/United Kingdom ; BB/H002731/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G0400192/MRC_/Medical Research Council/United Kingdom ; MC_G0802535/MRC_/Medical Research Council/United Kingdom ; MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom ; RG/18/7/33636/BHF_/British Heart Foundation/United Kingdom ; G0600717/MRC_/Medical Research Council/United Kingdom ; MC_UU_00014/2/MRC_/Medical Research Council/United Kingdom ; MRC_MC_UU_12012/2//Medical Research Council (MRC)/International ; RG/12/13/29853//BHF Centre of Research Excellence, Oxford (BHF Centre of Research Excellence in Oxford)/International ; }, mesh = {Adult ; Beverages ; Carnitine/analogs & derivatives/blood ; Case-Control Studies ; Cross-Over Studies ; Diabetes Mellitus/*metabolism ; Diet ; Fatty Acids/metabolism ; Female ; Humans ; Male ; Middle Aged ; Mitochondria/*metabolism ; Mitochondrial Dynamics ; Musa ; Oxygen/chemistry ; Stearic Acids/*metabolism ; }, abstract = {Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.}, } @article {pmid30085937, year = {2018}, author = {Zhou, T and Xu, D and Tang, B and Ren, Y and Han, Y and Liang, G and Wang, J and Wang, L}, title = {Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis.}, journal = {Anti-cancer drugs}, volume = {29}, number = {9}, pages = {904-910}, pmid = {30085937}, issn = {1473-5741}, mesh = {Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/*genetics ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*drug effects ; Risk Factors ; Triple Negative Breast Neoplasms/genetics/*pathology ; }, abstract = {The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 (P<0.05). The expression of PD-1 in the tumor-infiltrating immune cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 and the histological grade (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of PD-1 in paratumor-infiltrating immune cells (P<0.001). The expression of PD-L1 in tumor cells was found to be an independent prognostic risk factor with the progression-free survival rate for breast invasive ductal carcinoma (P=0.003). These results indicate that PD-L1 and PD-1 were highly expressed in TNBC which suggests that patients with TNBC may benefit from targeted immune therapies to a greater degree than patients with other subtypes. PD-L1 expression is an independent risk factor for breast invasive ductal carcinoma and expression of PD-L1 is expected to be a prognostic factor for breast cancer.}, } @article {pmid30078647, year = {2018}, author = {Deipolyi, AR and Riedl, CC and Bromberg, J and Chandarlapaty, S and Klebanoff, CA and Sofocleous, CT and Yarmohammadi, H and Brody, LA and Boas, FE and Ziv, E}, title = {Association of PI3K Pathway Mutations with Early Positron-Emission Tomography/CT Imaging Response after Radioembolization for Breast Cancer Liver Metastases: Results of a Single-Center Retrospective Pilot Study.}, journal = {Journal of vascular and interventional radiology : JVIR}, volume = {29}, number = {9}, pages = {1226-1235}, pmid = {30078647}, issn = {1535-7732}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/genetics/pathology ; Clinical Decision-Making ; DNA Mutational Analysis ; Embolization, Therapeutic/adverse effects/*methods ; Female ; Gene Expression Profiling ; Humans ; Liver Neoplasms/*diagnostic imaging/genetics/secondary/*surgery ; Middle Aged ; *Mutation ; New York City ; Patient Selection ; Phosphatidylinositol 3-Kinases/*genetics ; Pilot Projects ; *Positron Emission Tomography Computed Tomography ; Precision Medicine ; Predictive Value of Tests ; Preliminary Data ; Radiopharmaceuticals/*administration & dosage/adverse effects ; Retrospective Studies ; Risk Factors ; Signal Transduction/genetics ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.

MATERIALS AND METHODS: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.8) between January 2011 and September 2017 after receiving ≥ 3 lines of chemotherapy. Twenty-four underwent genetic profiling with MSK-IMPACT or Sequenom; 26 had positron-emission tomography (PET)/CT imaging before and after treatment. Survival after the first radioembolization and 2-4-month PET/CT imaging response were assessed. Laboratory and imaging features were assessed to determine variables predictive of outcomes. Unpaired Student t tests and Fisher exact tests were used to compare responders and nonresponders categorized by changes in fluorodeoxyglucose avidity. Kaplan-Meier survival analysis was used to determine the impact of predictors on survival after radioembolization.

RESULTS: Median survival after radioembolization was 11 months (range, 1-49 mo). Most patients (18 of 26; 69%) had complete or partial response based on changes in fluorodeoxyglucose avidity. Imaging response was associated with longer survival (P = .005). Whereas 100% of patients with PI3K pathway mutations showed an imaging response, only 45% of wild-type patients showed a response (P = .01). Median survival did not differ between PI3K pathway wild-type (10.9 mo) and mutant (undefined) patients (P = .50).

CONCLUSIONS: These preliminary data suggest that genomic profiling may predict which patients with metastatic breast cancer benefit most from radioembolization. PI3K pathway mutations are associated with improved imaging response, which is associated with longer survival.}, } @article {pmid30076656, year = {2018}, author = {Molière, S and Lodi, M and Roedlich, MN and Mathelin, C}, title = {Invasive ductal carcinoma limited to the nipple.}, journal = {The breast journal}, volume = {24}, number = {6}, pages = {1083}, doi = {10.1111/tbj.13090}, pmid = {30076656}, issn = {1524-4741}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Nipples/diagnostic imaging/*pathology ; }, } @article {pmid30073044, year = {2018}, author = {Anand, G and Al-Khalisi, N and Arif, D and Hamidpour, S and Lewis, T}, title = {Rare case of male breast intraductal papilloma progressing to invasive ductal carcinoma: A radiologic-pathologic correlation.}, journal = {Radiology case reports}, volume = {13}, number = {3}, pages = {602-605}, pmid = {30073044}, issn = {1930-0433}, abstract = {Although male breast cancer represents only 0.5%-1% of all breast cancer cases in the United States, the incidence of this disease is slowly rising [1]. Because of its extremely low prevalence, screening and treatment guidelines are not well established. Thus, analyzing cases of male breast cancer can accelerate this process. We present a case of a 52-year-old man, initially diagnosed with biopsy-confirmed intraductal papilloma without atypia, who presented 3 years later with progression of this benign lesion to ductal carcinoma in situ and development of de novo invasive ductal carcinoma. This report stresses the importance of symptom detection and risk factor modification with the goal of decreasing the incidence of this disease.}, } @article {pmid31595254, year = {2019}, author = {Moutinho-Guilherme, R and Oyola, JH and Sanz-Rosa, D and Vassallo, IT and García, RM and Pisco, JM and de Vega, VM}, title = {Correlation between apparent diffusion coefficient values in breast magnetic resonance imaging and prognostic factors of breast invasive ductal carcinoma.}, journal = {Porto biomedical journal}, volume = {4}, number = {1}, pages = {e27}, pmid = {31595254}, issn = {2444-8672}, abstract = {BACKGROUND: We wanted to examine whether the apparent diffusion coefficient values obtained by diffusion-weighted imaging techniques could indicate an early prognostic assessment for patients with Invasive Ductal Carcinoma and, therefore, influence the treatment decision making.

OBJECTIVE: The main objective was to evaluate the correlation between the apparent diffusion coefficient values obtained by diffusion-weighted imaging and the key prognostic factors in breast invasive ductal carcinoma. Secondary objectives were to analyze the eventual correlations between magnetic resonance imaging findings and prognostic factors in breast cancer; and to perform a comparison between results in 1.5 and 3.0 T scanners.

METHODS: Breast magnetic resonance imaging with diffusion-weighted imaging sequence was performed on 100 patients, who were proven histopathologically to have breast invasive ductal carcinoma. We compared the apparent diffusion coefficient values, obtained previous to biopsy, with the main prognostic factors in breast cancer: tumor size, histologic grade, hormonal receptors, Ki67 index, human epidermal growth factor receptor type 2, and axillary lymph node status. The Mann-Whitney U test and the Kruskal-Wallis analysis were used to establish these correlations.

RESULTS: The mean apparent diffusion coefficient value was inferior in the estrogen receptor-positive group than in the estrogen receptor-negative group (1.04 vs 1.17 × 10[-3] mm[2]/s, P = .004). Higher histologic grade related to larger tumor size (P = .002). We found association between spiculated margins and positive axillary lymph node status [odds ratio = 4.35 (1.49-12.71)]. There were no differences in apparent diffusion coefficient measurements between 1.5 and 3.0 T magnetic resonance imaging scanners (P = .513).

CONCLUSIONS: Low apparent diffusion coefficient values are related with positive expression of estrogen receptor. Larger tumors and spiculated margins are associated to worse prognosis. Rim enhancement is more frequently observed in estrogen receptor-negative tumors. There are no differences in apparent diffusion coefficient measurements between different magnetic resonance imaging scanners.}, } @article {pmid30071094, year = {2018}, author = {Hong, JH and Ko, YH and Kang, K}, title = {RNA variant identification discrepancy among splice-aware alignment algorithms.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0201822}, pmid = {30071094}, issn = {1932-6203}, mesh = {*Algorithms ; Breast/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Computational Biology/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; RNA/metabolism ; *RNA Splicing ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; }, abstract = {Next-generation sequencing (NGS) techniques have been generating various molecular maps, including transcriptomes via RNA-seq. Although the primary purpose of RNA-seq is to quantify the expression level of known genes, RNA variants are also identifiable. However, care must be taken to account for RNA's dynamic nature. In this study, we evaluated the following popular splice-aware alignment algorithms in the context of RNA variant-calling analysis: HISAT2, STAR, STAR (two-pass mode), Subread, and Subjunc. For this, we performed RNA-seq with ten pieces of invasive ductal carcinoma from breast tissue and three pieces of adjacent normal tissue from a single patient. These RNA-seq data were used to evaluate the performance of splice-aware aligners. Surprisingly, the number of common potential RNA editing sites (pRESs) identified by all alignment algorithms was less than 2% of the total. The main cause of this difference was the mapped reads on the splice junctions. In addition, the RNA quality significantly affected the outcome. Therefore, researchers must consider these experimental and bioinformatic features during RNA variant analysis. Further investigations of common pRESs discovered that BDH1, CCDC137, and TBC1D10A transcripts contained a single non-synonymous RNA variant that was unique to breast cancer tissue compared to adjacent normal tissue; thus, further clinical validation is required.}, } @article {pmid30069180, year = {2018}, author = {Shuja, J and Ahmad, I and Arshad, S and Manzoor, H and Kakar, S and Ahmad, K}, title = {A Case Report of Triple-Positive Micropapillary Carcinoma of the Male Breast.}, journal = {Breast care (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {192-194}, pmid = {30069180}, issn = {1661-3791}, abstract = {BACKGROUND: Micropapillary carcinoma (MPC), a morphologically distinct subtype of invasive ductal carcinoma, of the male breast is an exceedingly uncommon disease.

CASE REPORT: Herein, we report a case of triple-positive MPC of the male breast with axillary lymph node involvement and no recurrence for over 2 years. Specifically, a 60-year-old male patient presented with a hard, elastic, and well-defined painless mass in the right breast. The patient underwent unilateral (right) modified radical mastectomy with axillary clearance. Histopathology revealed MPC grade 3 and metastasis in 16/16 lymph nodes. Hormone receptor analysis demonstrated strong positivity (total score 08) for estrogen/progesterone receptors and overexpression (score 3+) of human epidermal growth factor receptor 2. The patient received adjuvant chemotherapy (6 courses of CAF: cyclophosphamide, doxorubicin, and 5-fluorouracil), radiation, and tamoxifen. The patient has remained disease-free for over 2 years.

CONCLUSION: This study demonstrates that triple-positive MPC of the male breast as a rare malignancy appears to respond promisingly to multimodality treatment.}, } @article {pmid30066839, year = {2018}, author = {Zhu, X and Zeng, Z and Qiu, D and Chen, J}, title = {Vγ9Vδ2 T cells inhibit immature dendritic cell transdifferentiation into osteoclasts through downregulation of RANK, c‑Fos and ATP6V0D2.}, journal = {International journal of molecular medicine}, volume = {42}, number = {4}, pages = {2071-2079}, pmid = {30066839}, issn = {1791-244X}, mesh = {Cell Transdifferentiation/*immunology ; Dendritic Cells/*immunology/pathology ; Humans ; Osteoclasts/*immunology/pathology ; Proto-Oncogene Proteins c-fos/*immunology ; Receptor Activator of Nuclear Factor-kappa B/*immunology ; Receptors, Antigen, T-Cell, gamma-delta/*immunology ; Signal Transduction/*immunology ; T-Lymphocytes/*immunology/pathology ; Vacuolar Proton-Translocating ATPases/*immunology ; }, abstract = {Osteoimmunological studies have revealed that T cells exert a powerful impact on the formation and activity of osteoclasts and bone remodeling. Evidence demonstrates that immature dendritic cells (iDCs) are more efficient transdifferentiating into osteoclasts (OCs) than monocytes. However, whether Vγ9Vδ2 T (γδ T) cells stimulate or inhibit iDC transdifferentiation into OCs has never been reported. The aim of the present study was to investigate the effects of γδ T cells on this transdifferentiation process. γδ T cells and iDCs were isolated from the peripheral blood of healthy volunteers separately and were co‑cultured with Transwelll inserts, with γδ T cells in the upper chamber and iDCs in the lower chamber. IDCs were treated with macrophage‑colony stimulating factor and receptor activator of nuclear factor‑κB (RANK) ligand. Tartrate resistant acid phosphatase (TRAP) assay and dentine resorption assay were performed to detect OC formation and their resorption capacity, respectively. The mRNA expression of OCs was examined using a microarray and real time‑quantitative polymerase chain reaction to trace the changes during iDC transdifferentiation into OCs. The results demonstrated that γδ T cells significantly inhibited the generation of the TRAP‑positive OCs from iDCs and their resorption capacity. The microarray analysis identified decreased expression level of Fos proto‑oncogene AP‑1 transcription factor subunit (c‑Fos), ATPase H+ transporting V0 subunit d (ATP6V0D2) and cathepsin K when iDCs were co‑cultured with γδ T cells. These genes are associated with OC differentiation, indicating that γδ T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/c‑Fos/ATP6V0D2 signaling pathway. The present findings provide novel insights into the interactions between human γδ T cells and iDCs, and demonstrate that γδ T cells are capable of inhibiting OC formation and their activity via downregulation of genes associated with OC differentiation.}, } @article {pmid30066480, year = {2018}, author = {Dodson, A and Parry, S and Ibrahim, M and Bartlett, JM and Pinder, S and Dowsett, M and Miller, K}, title = {Breast cancer biomarkers in clinical testing: analysis of a UK national external quality assessment scheme for immunocytochemistry and in situ hybridisation database containing results from 199 300 patients.}, journal = {The journal of pathology. Clinical research}, volume = {4}, number = {4}, pages = {262-273}, pmid = {30066480}, issn = {2056-4538}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/metabolism/pathology ; Databases, Factual ; Estrogen Receptor alpha/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ireland ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; United Kingdom ; }, abstract = {We describe a collated data set of results from clinical testing of breast cancers carried out between 2009 and 2016 in the United Kingdom and Republic of Ireland. More than 199 000 patient biomarker data sets, together with clinicopathological parameters were collected. Our analyses focused on human epidermal growth factor receptor-2 (HER2), oestrogen receptor (ER) and progesterone receptor (PR), with the aim of the study being to provide robust confirmatory evidence on known associations in these biomarkers and to uncover new data on previously undescribed or unconfirmed associations, thus strengthening the evidence-base in clinical breast cancer testing. Overall, 13.1% of tumours were HER2-positive; 10.6% in ER-positive tumours, and 25.5% in ER-negative tumours. Higher rates of HER2 positivity were significantly associated with patient age <56 years versus age ≥56 years, symptomatic versus screen-detected tumours, testing of involved axillary node versus primary breast cancer, invasive ductal carcinoma (not otherwise specified) versus other histological types, higher histological grade, increasing tumour size, increasing nodal involvement, ER-negative versus ER-positive tumour status, PR-negative versus PR-positive tumour status. Where ER status was known, 82.7% of tumours were ER-positive; 80.9% in women age <56 years, and 83.6% in those age ≥56 years (ER-positive cut-off ≥1.0% positive tumour cells or equivalent). Where PR status was known, 64.9% of tumours were PR-positive; 65.8% in women age <56 years, and 64.4% in women age ≥56 years (PR-positive cut off ≥10.0% or equivalent). These analyses of clinical test results provide contemporary benchmarking data for HER2, ER and PR positive rates.}, } @article {pmid30064485, year = {2018}, author = {Hashmi, AA and Aijaz, S and Mahboob, R and Khan, SM and Irfan, M and Iftikhar, N and Nisar, M and Siddiqui, M and Edhi, MM and Faridi, N and Khan, A}, title = {Clinicopathologic features of invasive metaplastic and micropapillary breast carcinoma: comparison with invasive ductal carcinoma of breast.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {531}, pmid = {30064485}, issn = {1756-0500}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; *Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVES: The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS).

RESULTS: 86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER negative and 86% were PR negative, respectively as compared to ductal carcinoma NOS, which were 40% ER negative and 54% were PR. Similarly, 86.7% micropapillary cancers were ER positive and 73.3% were PR positive. Moreover, 66.7% micropapillary carcinoma showed nodal metastasis and 77.8% showed lymphovascular invasion, which was significantly higher than that of IDC, NOS micropapillary and metaplastic carcinomas accounts for less than 2 and 1% of the breast cancer burden in our population and highly correlates with poor prognosis parameters therefore, require more intensive management in our population.}, } @article {pmid30063890, year = {2018}, author = {Papadopoulos, EI and Papachristopoulou, G and Ardavanis, A and Scorilas, A}, title = {A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance.}, journal = {Clinical biochemistry}, volume = {60}, number = {}, pages = {24-32}, doi = {10.1016/j.clinbiochem.2018.07.008}, pmid = {30063890}, issn = {1873-2933}, mesh = {Adenofibroma/diagnosis/*genetics/pathology ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Carcinoma, Lobular/diagnosis/genetics/pathology ; Diagnosis, Differential ; Female ; Humans ; MicroRNAs/*genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors.

METHODS: The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients.

RESULTS: Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P = 0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P = 0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P = 0.026) and 0.663 (P = 0.001), respectively. Furthermore, miR-331 levels were elevated (P = 0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients.

CONCLUSIONS: Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.}, } @article {pmid30061943, year = {2018}, author = {Peng, Y and Luo, ZY and Ni, J and Cui, HD and Lu, B and Xiang, AZ and Zhou, J and Ding, JW and Chen, WH and Zhao, J and Fang, JH and Zhao, P}, title = {Precision biopsy of breast microcalcifications: An improvement in surgical excision.}, journal = {Oncology letters}, volume = {16}, number = {1}, pages = {1212-1218}, pmid = {30061943}, issn = {1792-1074}, abstract = {The aim of the present study was to improve the conventional wire-guided localization biopsy (WGLB) of breast microcalcifications to overcome disadvantages associated with the procedure, including inaccurate localization and large specimen volume. The novel approach described in the present study was termed double wire-guided localization and rotary cutting biopsy (DWGLB). Prior to surgery, the precise localization of the lesions was assessed using two wires under the assistance of mammography X-ray and ultrasound, followed by complete excision of the lesions using a novel rotary cutting tool. The cylindrical specimen was placed on a scaled specimen holder for pathological examination. DWGLB was performed in 108 patients with the classification of as Breast Imaging Reporting and Data System score 4A. Percutaneous localization of the lesions guided by a mammography X-ray and ultrasound were successful in all 108 lesions (100%) with one puncture attempt. The lesions were precisely excised in all of 108 patients, and included 13 malignant lesions (DCIS of breast in 7 cases, DCIS with focal invasive carcinoma in 3 cases and invasive ductal carcinoma in 3 cases). The average distance of the BARD Dualok to the lesion was 4.1 mm; the average weight of specimens was 8.5 g. Compared with WGLB, DWGLB offers several advantages, including more accurate localization of lesions, a more standardized biopsy method and a smaller specimen volume. DWGLB can also provide the precise position of lesions in the specimen for further pathological examination.}, } @article {pmid30061491, year = {2018}, author = {Rucco, R and Sorriso, A and Liparoti, M and Ferraioli, G and Sorrentino, P and Ambrosanio, M and Baselice, F}, title = {Correction: Rucco, R.; et al. Type and Location of Wearable Sensors for Monitoring Falls during Static and Dynamic Tasks in Healthy Elderly: A Review. Sensors 2018, 18, 1613.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {8}, pages = {}, pmid = {30061491}, issn = {1424-8220}, abstract = {The authors wish to make a correction to their paper [1]. The following Table 1 should be replaced with the table shown below it[...].}, } @article {pmid30061271, year = {2018}, author = {Fujii, T and Yanai, K and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Hirakata, T and Shirabe, K}, title = {Relationship Between FDG Uptake and Neutrophil/Lymphocyte Ratio in Patients with Invasive Ductal Breast Cancer.}, journal = {Anticancer research}, volume = {38}, number = {8}, pages = {4927-4931}, doi = {10.21873/anticanres.12809}, pmid = {30061271}, issn = {1791-7530}, mesh = {C-Reactive Protein/analysis ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Fluorodeoxyglucose F18/administration & dosage/*metabolism ; Glucose/*metabolism ; Humans ; Lymphatic Metastasis ; Lymphocyte Count ; Lymphocytes/*cytology ; Middle Aged ; Neoplasm Grading ; Neutrophils/*cytology ; Positron Emission Tomography Computed Tomography/methods ; Radiopharmaceuticals/administration & dosage/*metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: [18]F-Fluorodeoxyglucose-positron-emission tomography (FDG-PET) is used to evaluate the glucose metabolic rates of tumors. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. FDG uptake is influenced by many factors, including inflammation. In this study, the relationship between FDG uptake and neutrophil/lymphocyte ratio (NLR), which is an indicator of systemic inflammation, was investigated.

PATIENTS AND METHODS: A retrospective investigation of the cases of 143 consecutive patients with invasive ductal carcinoma who had undergone surgery and FDG-PET preoperatively. PET was evaluated using standardized uptake value max (SUVmax). The median SUVmax was 2.5 (range=0-10.5). The cases were divided into two groups based on the value of SUVmax: low (<2.5) and high (≥2.5). The relationships between SUVmax and clinicopathological features, including NLR, were investigated.

RESULTS: Among the 143 patients, 73 (51.0%) had high SUVmax in the primary tumor. The analysis revealed that large tumor size (p<0.001), high nuclear grade (p<0.001), the presence of lymphovascular invasion (p<0.001), high C-reactive protein (p=0.046) and high NLR (p<0.001) were significantly associated with high SUVmax in the primary tumor. SUVmax and NLR were significantly positively correlated (r=0.323, p<0.001). Among the 70 cases with low SUVmax, there was no recurrent disease, while out of the 73 cases with high SUVmax had disease recurrence. It is interesting to note that the group with high SUVmax and low NLR had no recurrent disease.

CONCLUSION: The present study demonstrated that the finding of high preoperative FDG uptake in breast cancer may be reflective of poor prognosis and that a high NLR may be predictive of aggressive features among patients with breast cancer. On the other hand, among patients with breast cancer with high SUVmax in the primary tumor, it will be useful to identify those with a low NLR in order to improve prognostic accuracy.}, } @article {pmid30060783, year = {2018}, author = {Lateef, F and Jamal, S and Nasir, S}, title = {Her-2/neu Oncogene Amplification by Fluorescence In Situ Hybridization and Protein Overexpression on Immunohistochemistry in Breast Cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {28}, number = {8}, pages = {581-585}, doi = {10.29271/jcpsp.2018.08.581}, pmid = {30060783}, issn = {1681-7168}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/*pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Cross-Sectional Studies ; DNA, Neoplasm/analysis ; Female ; *Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/*methods ; Middle Aged ; Receptor, ErbB-2/*genetics/metabolism ; }, abstract = {OBJECTIVE: To investigate the concordance and discordance between the test results of Her-2/neu by immunohisto-chemistry (IHC) and flourescence In Situ hybridization (FISH) in breast cancer cases.

STUDY DESIGN: Descriptive cross-sectional study.

PLACE AND DURATION OF STUDY: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, from 2011 to 2016.

METHODOLOGY: Forty-three specimens of invasive ductal carcinoma of breast were evaluated for grade and Her-2/neu status using IHC and FISH methods. Concordance and discordance between their results was determined.

RESULTS: There is 100% concordance between FISH and IHC in cases scoring 0, 1+ (negative) and 3+ (positive) immunostaining. Tumour cases scoring 2+ immunostaining showed amplification in 69.2% cases. All grade-I tumours were non-amplified on FISH, while most of the grade-III tumours showed Her-2/neu amplification on FISH. There is significant association of Her-2/neu IHC with tumour grade and FISH (p<0.05). A fairly high proportion i.e. 69.7% of cases showed Her-2/neu gene amplification. There was high concordance between Her-2/neu testing on IHC and FISH, (Kappa co-efficient 0.466, p <0.001).

CONCLUSION: Her-2/neu amplification increases with increasing grade of breast cancer. A high proportion of Her-2/neu gene amplified cases indicates aggressive disease in that area and need for FISH testing on large scale, which is the gold standard for equivocal cases on immunohistochemistry.}, } @article {pmid30056557, year = {2019}, author = {Brock, EJ and Ji, K and Shah, S and Mattingly, RR and Sloane, BF}, title = {In Vitro Models for Studying Invasive Transitions of Ductal Carcinoma In Situ.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {24}, number = {1}, pages = {1-15}, pmid = {30056557}, issn = {1573-7039}, support = {P30 CA22453/NH/NIH HHS/United States ; U54 CA193489/NH/NIH HHS/United States ; T32 CA009531/NH/NIH HHS/United States ; R01 CA131990/NH/NIH HHS/United States ; P30 ES006639/ES/NIEHS NIH HHS/United States ; R21 CA175931/CA/NCI NIH HHS/United States ; R21 CA175931/NH/NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; U54 CA193489/CA/NCI NIH HHS/United States ; F31 CA213807/CA/NCI NIH HHS/United States ; F31 CA213807/NH/NIH HHS/United States ; T32 CA009531/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; }, mesh = {Breast/pathology ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/*pathology ; Cell Line, Tumor ; Coculture Techniques/methods ; Drug Screening Assays, Antitumor/methods ; Female ; Humans ; Neoplasm Invasiveness/pathology/prevention & control ; Primary Cell Culture/*methods ; }, abstract = {About one fourth of all newly identified cases of breast carcinoma are diagnoses of breast ductal carcinoma in situ (DCIS). Since we cannot yet distinguish DCIS cases that would remain indolent from those that may progress to life-threatening invasive ductal carcinoma (IDC), almost all women undergo aggressive treatment. In order to allow for more rational individualized treatment, we and others are developing in vitro models to identify and validate druggable pathways that mediate the transition of DCIS to IDC. These models range from conventional two-dimensional (2D) monolayer cultures on plastic to 3D cultures in natural or synthetic matrices. Some models consist solely of DCIS cells, either cell lines or primary cells. Others are co-cultures that include additional cell types present in the normal or cancerous human breast. The 3D co-culture models more accurately mimic structural and functional changes in breast architecture that accompany the transition of DCIS to IDC. Mechanistic studies of the dynamic and temporal changes associated with this transition are facilitated by adapting the in vitro models to engineered microfluidic platforms. Ultimately, the goal is to create in vitro models that can serve as a reproducible preclinical screen for testing therapeutic strategies that will reduce progression of DCIS to IDC. This review will discuss the in vitro models that are currently available, as well as the progress that has been made using them to understand DCIS pathobiology.}, } @article {pmid30051683, year = {2018}, author = {Solanki, R and Agrawal, N and Ansari, M and Jain, S and Jindal, A}, title = {COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {19}, number = {7}, pages = {1971-1975}, pmid = {30051683}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cyclooxygenase 2/*metabolism ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; }, abstract = {Objective: Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters. Methods: Radical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated. Result: The results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium. Conclusion: Our study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.}, } @article {pmid30050604, year = {2018}, author = {Guennoun, A and Krimou, Y and Bouchikhi, C and Mamouni, N and Errarhay, S and Banani, A}, title = {[Radio-histological correlation of ACR4 microcalcifications in breast lesions: about 181 cases and literature review].}, journal = {The Pan African medical journal}, volume = {29}, number = {}, pages = {140}, pmid = {30050604}, issn = {1937-8688}, mesh = {Adenofibroma/diagnostic imaging/epidemiology/pathology ; Adolescent ; Adult ; Aged ; Breast Diseases/*diagnostic imaging/epidemiology/pathology ; Breast Neoplasms/*diagnostic imaging/epidemiology/pathology ; Calcinosis/*diagnostic imaging/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/epidemiology/pathology ; Female ; Hospitals, University ; Humans ; Mass Screening/methods ; Middle Aged ; Morocco/epidemiology ; Predictive Value of Tests ; Retrospective Studies ; Young Adult ; }, abstract = {The Bi-RADS (Breast Imaging Reporting and Data System) classification developed by the ACR (American College of Radiology) is the classification system for radiological images recommended for breast cancer screening. The ACR 4 microcalcification is an indeterminate or suspected abnormality with 2-95% probability of malignancy, according to studies. This disparity pushed us to conduct this retrospective study of 181 patients in the Department of Obstetrics and Gynecology I at the Hassan II University Hospital, Fez, over a period of 5 years. This study aimed to report the histological results of breast lesions radiologically classified as ACR4 in order to assess their radio-histological correlation and to improve therapeutic approach. All patients underwent breast imaging examinations and then anatomopathologic examination was performed using different techniques. There was a clear predominance of benign lesions with a rate of 62% versus 29% of malignant lesions and only 9% were intermediate lesions. Adenofibroma was the most common histological finding (30% of cases), invasive ductal carcinoma was the most frequent malignant lesion (17% of cases). We performed a literature review which showed that our results were in line with findings of other studies, with a positive predictive value of 29%. Nevertheless, ACR classification divided into subcategories 4a, b and c should be used due to the significant number of unnecessary surgical interventions.}, } @article {pmid30050552, year = {2018}, author = {Bai, G and Jenkins, S and Yuan, W and Graef, GL and Ge, Y}, title = {Field-Based Scoring of Soybean Iron Deficiency Chlorosis Using RGB Imaging and Statistical Learning.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {1002}, pmid = {30050552}, issn = {1664-462X}, abstract = {Iron deficiency chlorosis (IDC) is an abiotic stress in soybean that can cause significant biomass and yield reduction. IDC is characterized by stunted growth and yellowing and interveinal chlorosis of early trifoliate leaves. Scoring IDC severity in the field is conventionally done by visual assessment. The goal of this study was to investigate the usefulness of Red Green Blue (RGB) images of soybean plots captured under the field condition for IDC scoring. A total of 64 soybean lines with four replicates were planted in 6 fields over 2 years. Visual scoring (referred to as Field Score, or FS) was conducted at V3-V4 growth stage; and concurrently RGB images of the field plots were recorded with a high-throughput field phenotyping platform. A second set of IDC scores was done on the plot images (displayed on a computer screen) consistently by one person in the office (referred to as Office Score, or OS). Plot images were then processed to remove weeds and extract six color features, which were used to train computer-based IDC scoring models (referred to as Computer Score, or CS) using linear discriminant analysis (LDA) and support vector machine (SVM). The results showed that, in the fields where severe IDC symptoms were present, FS and OS were strongly positively correlated with each other, and both of them were strongly negatively correlated with yield. CS could satisfactorily predict IDC scores when evaluated using FS and OS as the reference (overall classification accuracy > 81%). SVM models appeared to outperform LDA models; and the SVM model trained to predict IDC OS gave the highest prediction accuracy. It was anticipated that coupling RGB imaging from the high-throughput field phenotyping platform with real-time image processing and IDC CS models would lead to a more rapid, cost-effective, and objective scoring pipeline for soybean IDC field screening and breeding.}, } @article {pmid30049563, year = {2019}, author = {Lee, SB and Yu, JH and Park, H and Kim, HJ and Park, SH and Chae, BJ and Youn, HJ and Jung, SY and Kim, EK and Jung, YS and Son, BH}, title = {Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer with axillary node metastasis: A survey of clinical practice.}, journal = {Asian journal of surgery}, volume = {42}, number = {1}, pages = {314-319}, doi = {10.1016/j.asjsur.2018.06.004}, pmid = {30049563}, issn = {0219-3108}, mesh = {Axilla ; Breast Neoplasms/*pathology/*therapy ; *Chemotherapy, Adjuvant ; Female ; Humans ; Korea ; Lymph Node Excision/*statistics & numerical data ; Lymph Nodes/*pathology ; *Lymphatic Metastasis ; Mastectomy/methods ; *Neoadjuvant Therapy ; *Practice Patterns, Physicians' ; *Sentinel Lymph Node Biopsy/statistics & numerical data ; *Surgeons ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: A survey of breast surgeons was conducted to evaluate changes in clinical practice regarding sentinel node biopsy (SNB) among clinically node-negative patients after neoadjuvant chemotherapy for breast cancer with axillary node metastasis.

METHODS: We conducted two surveys among 252 members of the Korean Breast Cancer Society. The questionnaire comprised a case presentation and two associated questions. The case outlined a woman diagnosed with right breast cancer; core needle biopsy had confirmed invasive ductal carcinoma and tumor size was 4 cm on imaging examination. Fine needle aspiration examination for axillary lymph node enlargement showed metastatic carcinoma. The patient underwent neoadjuvant chemotherapy and tumor size was decreased by 2 cm; axillary lymph node enlargement was not observed on palpitation or imaging examination. Finally, the patient underwent breast conserving surgery. Survey recipients were asked: 1. Would you perform SNB in this patient? 2. If you perform SNB and no axillary node metastasis is seen, would you perform additional axillary lymph node dissection (ALND)?

RESULTS: The response rate was 28.2% (71/252) and 15.1% (38/252) in 2013 and 2017, respectively. For the first question, the SNB to ALND ratio increased significantly from 54% versus 46% in 2013 to 92% versus 8% in 2017 (p < 0.001). The proportion of surgeons performing no additional ALND versus additional ALND increased from 38% versus 54% in 2013 to 53% versus 37% in 2017, but did not reach statistical significance (p = 0.1).

CONCLUSIONS: These data show that application of SNB among clinically node-negative patients after neoadjuvant chemotherapy for breast cancer with node metastasis has increased among surgeons in Korea.}, } @article {pmid30046204, year = {2018}, author = {Zangouri, V and Akrami, M and Tahmasebi, S and Talei, A and Ghaeini Hesarooeih, A}, title = {Medullary Breast Carcinoma and Invasive Ductal Carcinoma: A Review Study.}, journal = {Iranian journal of medical sciences}, volume = {43}, number = {4}, pages = {365-371}, pmid = {30046204}, issn = {0253-0716}, abstract = {BACKGROUND: Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. The present study aimed to evaluate the classic and non-classic characteristics of MBC and its differences with IDC. The present review study incorporates 22 years of practical experience from a breast disease research center-based series of cases.

METHODS: Retrospectively, the medical records of 3,246 patients were reviewed in the Breast Disease Research Center, Shiraz University of Medical Science (Shiraz, Iran), from December 1993 to December 2015. The tumor size, lymph node metastasis, pathologic stage, nuclear and histological grade, hormonal receptor status, recurrence, disease-free, and overall survival were reviewed. Differences between medullary breast carcinoma and invasive ductal carcinoma were analyzed statistically using the Chi-square, Fischer, independent-sample t test, and Kaplan-Meier analysis (SPSS version 19.0). P<0.05 were considered statistically significant.

RESULTS: A total of 179 patients were identified with MBC and 3,067 patients were identified with IDC. The MBC group had a significant association with a higher histological grade (P<0.001) as well as negative estrogen receptor (P<0.001), progesterone receptor (P<0.001), and HER-2 (P=0.004) status. The MBC patients predominantly had triple-negative breast cancer (TNBC) according to the molecular subtype (P<0.001). In local invasion, MBC was less invasive compared to IDC (P<0.001). The disease-free survival (DFS) and overall survival (OS) differed significantly between the MBC and IDC groups (5-year DFS: 94.2% vs. 86.3%, P=0.008; 5-year OS: 98.1% vs. 92.8%, P=0.004).

CONCLUSION: Despite the poor and aggressive pathological features of MBC, its clinical outcome is more favorable compared to IDC. Our findings can be useful in improvement of diagnosis and treatment of less known breast cancer subtypes, such as MBC.}, } @article {pmid30042281, year = {2018}, author = {Ishikawa, N and Saimura, M and Koga, K and Anan, K and Mitsuyama, S and Tamiya, S}, title = {[A Case of Metaplastic Squamous Cell Carcinoma of the Breast Diagnosed after Neoadjuvant Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {7}, pages = {1101-1103}, pmid = {30042281}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/surgery ; Carcinoma, Squamous Cell/*drug therapy/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoadjuvant Therapy ; Treatment Outcome ; }, abstract = {Metaplastic carcinoma is a rare type of breast carcinoma, which tends to be chemo-resistant. We report a case of metaplastic squamous cell carcinoma of the breast diagnosed after neoadjuvant chemotherapy(NAC). A 56-year-old woman was diagnosed as having right-sided breast cancer(invasive ductal carcinoma[IDC], triple negative), cT1cN1M0, stage II A. NAC with 5-fluorouracil, epirubicin, and cyclophosphamide(FEC)followed by docetaxel(DTX)was administered. Tumor progression occurred during both the FEC and DTX regimens. We discontinued NAC and performed breast conserving surgery with axillary lymph node dissection. Histological findings of the resected specimen showed mixed IDC and widely spread squamous metaplasia. Weekly paclitaxel and radiotherapy were administered and the patient is alive with no recurrence 3 years after surgery.}, } @article {pmid30039376, year = {2018}, author = {Bang, S and Lee, C and Ryu, J and Li, W and Koh, YS and Jeon, JH and Lee, J and Shim, SH}, title = {Simultaneous determination of the bioactive compounds from Sparassis crispa (Wulf.) by HPLC-DAD and their inhibitory effects on LPS-stimulated cytokine production in bone marrow-derived dendritic cell.}, journal = {Archives of pharmacal research}, volume = {41}, number = {8}, pages = {823-829}, doi = {10.1007/s12272-018-1054-y}, pmid = {30039376}, issn = {1976-3786}, support = {116001-3//Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries/ ; National Research Council of Science & Technology//National Research Council of Science and Technology/ ; }, mesh = {Agaricales/*chemistry ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/isolation & purification/*pharmacology ; Biological Products/chemistry/isolation & purification/*pharmacology ; Bone Marrow Cells/*cytology ; Cell Survival/drug effects ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Cytokines/*biosynthesis ; Dendritic Cells/cytology/*drug effects/*metabolism ; Dose-Response Relationship, Drug ; Lipopolysaccharides/*antagonists & inhibitors/pharmacology ; Mice ; Mice, Inbred C57BL ; Molecular Structure ; Structure-Activity Relationship ; }, abstract = {Sparassis crispa (Wulf.) belonging to the family of Sparassidaceae, has been widely used as an edible mushroom due to its unique flavor and functions to improve health. In this study, the compounds isolated from the extract of this mushroom were simultaneously quantified by the developed HPLC-DAD method and evaluated for the inhibitory activities on the production of the LPS-stimulated cytokines (IL-12p40, IL-6, and TNF-α) in bone marrow-derived dendritic cells (BMDCs). The contents of this compounds were 0.1928 ± 0.0118, 4.4137 ± 0.0240, 0.5237 ± 0.0005, 2.7303 ± 0.0206 mg/g for sparoside A (1), methyl 2,4-dihydroxy-3-methoxy-6-methylbenzoate (2), sparalide A (3), and 5'-deoxy-5'-methylthioadenosine (4), respectively, which demonstrated that they are the major constituents of this mushroom. Thus, our results were found that the sparoside A (1), 5-hydroxy-7-methoxyphthalide (6), 5-methoxy-7-hydroxyphthalide (7), nicotinamide (10), and adenosine (11) inhibit LPS-stimualted cytokine production, compound 6 is the most potent inhibitory activities on the production of IL-12p40, IL-6, and TNF-α with IC50 values of 0.19, 0.18, and 0.91 μM, respectively.}, } @article {pmid30036996, year = {2018}, author = {Seimon, RV and Gibson, AA and Harper, C and Keating, SE and Johnson, NA and da Luz, FQ and Fernando, HA and Skilton, MR and Markovic, TP and Caterson, ID and Hay, P and Byrne, NM and Sainsbury, A}, title = {Rationale and Protocol for a Randomized Controlled Trial Comparing Fast versus Slow Weight Loss in Postmenopausal Women with Obesity-The TEMPO Diet Trial.}, journal = {Healthcare (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {30036996}, issn = {2227-9032}, abstract = {Very low energy diets (VLEDs), commonly achieved by replacing all food with meal replacement products and which result in fast weight loss, are the most effective dietary obesity treatment available. VLEDs are also cheaper to administer than conventional, food-based diets, which result in slow weight loss. Despite being effective and affordable, these diets are underutilized by healthcare professionals, possibly due to concerns about potential adverse effects on body composition and eating disorder behaviors. This paper describes the rationale and detailed protocol for the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity), in a randomized controlled trial comparing the long-term (3-year) effects of fast versus slow weight loss. One hundred and one post-menopausal women aged 45[-]65 years with a body mass index of 30[-]40 kg/m[2] were randomized to either: (1) 16 weeks of fast weight loss, achieved by a total meal replacement diet, followed by slow weight loss (as for the SLOW intervention) for the remaining time up until 52 weeks ("FAST" intervention), or (2) 52 weeks of slow weight loss, achieved by a conventional, food-based diet ("SLOW" intervention). Parameters of body composition, cardiometabolic health, eating disorder behaviors and psychology, and adaptive responses to energy restriction were measured throughout the 3-year trial.}, } @article {pmid30033677, year = {2018}, author = {Damin, AP and Pozzer, CL and Farret, TF and Reginatto, AG and Trindade, EN}, title = {Gigantic invasive ductal carcinoma of the breast.}, journal = {The breast journal}, volume = {24}, number = {6}, pages = {1082}, doi = {10.1111/tbj.13087}, pmid = {30033677}, issn = {1524-4741}, mesh = {Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Female ; Humans ; Lung Neoplasms/drug therapy/secondary ; Middle Aged ; }, } @article {pmid30029824, year = {2018}, author = {Yu, TJ and Liu, YY and Hu, X and Di, GH}, title = {Survival following breast-conserving therapy is equal to that following mastectomy in young women with early-stage invasive lobular carcinoma.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {44}, number = {11}, pages = {1703-1707}, doi = {10.1016/j.ejso.2018.06.026}, pmid = {30029824}, issn = {1532-2157}, mesh = {Adult ; Age Factors ; Breast Neoplasms/*mortality/radiotherapy/*surgery ; Carcinoma, Lobular/*mortality/radiotherapy/*surgery ; Female ; Humans ; Mastectomy/*mortality ; Mastectomy, Segmental/*mortality ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; SEER Program ; Survival Rate ; United States/epidemiology ; }, abstract = {BACKGROUND: Previous observational studies reported the superior survival of patients with early-stage breast cancer who underwent breast-conserving therapy (BCT, lumpectomy plus postsurgical radiation) compared to that of those who underwent mastectomy. Invasive lobular carcinoma (ILC) is not the same disease as invasive ductal carcinoma (IDC) as it has distinct biologic features and thus requires unique consideration and research.

METHODS: We selected women (≤50 years of age) from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with stage T1-2, N0-1, M0 primary breast cancer with invasive lobular features between 1998 and 2011, that were treated with either BCT or mastectomy with and without radiation. We assessed survival proportions using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models. Breast cancer-specific survival (BCSS) served as the primary endpoint.

RESULTS: A total of 3393 eligible young ILC patients were identified, 1391 (41%) of which underwent lumpectomy followed by radiation. The 10-year BCSS rates for patients who received BCT, mastectomy alone and mastectomy with radiation were 95.7%, 94.2% and 89.3%, respectively. Multivariate analysis showed that BCSS was not improved in patients assigned to mastectomy alone group (HR = 0.86; 95% CI 0.57-1.28) or mastectomy with postsurgical radiation group (HR = 0.97; 95% CI 0.58-1.62) compared to that in those who underwent BCT. The results did not changed when evaluating the 1998-2004 and 2005-2011 time periods separately.

CONCLUSION: None of the treatment demonstrated an absolute superiority in young women with early-stage ILC. Future studies with more detailed analyses of the confounding factors are worthwhile.}, } @article {pmid30028473, year = {2018}, author = {Gabanti, E and Lilleri, D and Scaramuzzi, L and Zelini, P and Rampino, T and Gerna, G}, title = {Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {195-202}, pmid = {30028473}, issn = {1121-7138}, mesh = {Adolescent ; Adult ; Aged ; Cytokines/*physiology ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/blood/*immunology ; Female ; Flow Cytometry ; Humans ; Immunity, Cellular ; Immunoassay/methods ; *Kidney Transplantation ; Male ; Middle Aged ; Sensitivity and Specificity ; T-Lymphocytes/*physiology ; *Transplant Recipients ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, <3x105 DNA copies/mL) self-resolving infection, 19 (36%) high viral load (HVL, >3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types.}, } @article {pmid30026605, year = {2018}, author = {Sen, U and Saxena, H and Khurana, J and Nayak, A and Gupta, A}, title = {Plasmodium falciparum RUVBL3 protein: a novel DNA modifying enzyme and an interacting partner of essential HAT protein MYST.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {10917}, pmid = {30026605}, issn = {2045-2322}, support = {SB/YS/LS-297/2013//Department of Science and Technology, Ministry of Science and Technology (DST)/International ; BT/08/IYBA/2014-4//Department of Biotechnology, Ministry of Science and Technology (DBT)/International ; }, mesh = {ATPases Associated with Diverse Cellular Activities/chemistry ; Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry ; Chromatin Assembly and Disassembly ; DNA/*metabolism ; DNA Helicases/chemistry ; Fungal Proteins/chemistry ; Gene Expression Regulation, Developmental ; Histone Acetyltransferases/*metabolism ; Histones/metabolism ; Models, Molecular ; Plasmodium falciparum/chemistry/genetics/*metabolism ; Protein Domains ; Protozoan Proteins/chemistry/genetics/metabolism ; Sequence Homology, Nucleic Acid ; Yeasts/chemistry/metabolism ; }, abstract = {RUVBLs constitute a conserved group of ATPase proteins that play significant role in a variety of cellular processes including transcriptional regulation, cell cycle and DNA damage repair. Three RUVBL homologues, namely, PfRUVBL1, PfRUVBL2 and PfRUVBL3 have been identified in P. falciparum, unlike its eukaryotic counterparts, which have two RUVBL proteins (RUVBL1 & RUVBL2). The present study expands our understanding of PfRUVBL3 protein and thereby basic biology of Plasmodium in general. Here, we have shown that parasite PfRUVBL3 is a true homolog of human/yeast RUVBL2 protein. Our result show that PfRUVBL3 constitutively expresses throughout the stages of intra-erythrocytic cycle (IDC) with varied localization. In addition to ATPase and oligomerization activity, we have for the first time shown that PfRUVBL3 possess DNA cleavage activity which interestingly is dependent on its insertion domain. Furthermore, we have also identified RUVBL3 to be an interacting partner of an essential chromatin remodeling protein PfMYST and together they colocalize with H3K9me1 histone in parasitophorous vacuole during the ring stage of IDC suggesting their potential involvement in chromatin remodeling and gene transcription.}, } @article {pmid30024024, year = {2019}, author = {Brunstein Klomek, A and Barzilay, S and Apter, A and Carli, V and Hoven, CW and Sarchiapone, M and Hadlaczky, G and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, PA and Cosman, D and Haring, C and Banzer, R and McMahon, E and Keeley, H and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D}, title = {Bi-directional longitudinal associations between different types of bullying victimization, suicide ideation/attempts, and depression among a large sample of European adolescents.}, journal = {Journal of child psychology and psychiatry, and allied disciplines}, volume = {60}, number = {2}, pages = {209-215}, doi = {10.1111/jcpp.12951}, pmid = {30024024}, issn = {1469-7610}, mesh = {Adolescent ; Bullying/*statistics & numerical data ; Crime Victims/*statistics & numerical data ; Depression/*epidemiology ; Europe ; Female ; Humans ; Longitudinal Studies ; Male ; *Suicidal Ideation ; Suicide, Attempted/*statistics & numerical data ; }, abstract = {BACKGROUND: The association between bullying victimization and depression, suicide ideation and suicide attempts has been studied mainly in cross-sectional studies. This study aims to test the bidirectional effect and the chronicity versus sporadic effect of physical, verbal, and relational bullying victimization on suicidal ideation/attempts and depression.

METHODS: Longitudinal assessments with an interval of 3- and 12-months were performed within a sample of 2,933 adolescents (56.1% females; mean age 14.78, SD = .89) from 10 European countries, participating in the Saving and Empowering Young Lives in Europe (SEYLE) school-based multicenter control sample. Multilevel Structural Equation Models were used, controlling for sociodemographic variables. Victimization was considered chronic when a student was victimized in the first two time points and sporadic when it was reported only at one point but not in another.

RESULTS: Bidirectional prospective association between all types of victimization and depression were found. Among participants, who reported victimization once (but not twice), physical victimization, but not verbal and relational, was associated with later suicidal ideation and attempts. Chronic victimization of any type increased likelihood for later depression compared with sporadic and no-victimization. Chronic relational victimization increased the likelihood of later suicidal ideation, and chronic physical victimization increased the likelihood for suicidal attempts.

CONCLUSIONS: The results support the bidirectional effect of victimization and depression and indicate that there are complex longitudinal associations between victimization and suicidal ideation/attempts. Physical victimization may especially carry effect on suicidal risk over time. Interventions should focus on victimization as a cause of distress but also aim to prevent vulnerable adolescents from becoming targets of victimization.}, } @article {pmid30017264, year = {2018}, author = {Diao, W and Tian, F and Jia, Z}, title = {The prognostic value of SUVmax measuring on primary lesion and ALN by [18]F-FDG PET or PET/CT in patients with breast cancer.}, journal = {European journal of radiology}, volume = {105}, number = {}, pages = {1-7}, doi = {10.1016/j.ejrad.2018.05.014}, pmid = {30017264}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/pathology ; Breast Neoplasms/*diagnostic imaging/mortality/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/mortality/pathology ; Disease-Free Survival ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Recurrence, Local/diagnostic imaging/mortality/pathology ; Positron Emission Tomography Computed Tomography/methods/mortality ; Positron-Emission Tomography/*methods/mortality ; Prognosis ; Proportional Hazards Models ; *Radiopharmaceuticals ; Young Adult ; }, abstract = {PURPOSE: To evaluate the prognostic value of maximum standardized uptake values (SUVmax) measured in the primary lesion and axillary lymph nodes (ALN) by pretreatment fluorine-18-fluorodeoxyglucose ([18]F-FDG) positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) in patients with breast cancer.

METHODS: We systematically searched PubMed, Embase, and the Cochrane Library. The primary prognosis endpoint was event-free survival (EFS), and the secondary endpoint was overall survival (OS). The pooled hazard ratio (HR) was estimated by using random-effects model according to the results of heterogeneity.

RESULTS: Fifteen eligible studies with 3574 breast cancer patients were included. For EFS, patients with higher primary SUVmax showed a poorer survival prognosis with pooled HR of 1.96 (95% confidence interval (CI) 1.40-2.73). The combined HR of high SUVmax in ALN and ALN-to-primary SUVmax ratio (N/T ratio) were 1.89 (95% CI 0.70-5.07) and 2.06 (95% CI 0.59-7.21), respectively. In analyzing invasive ductal carcinoma (IDC) patients, the pooled HR was 1.91 (95% CI 1.40-2.64). For OS, the pooled HR of SUVmax in primary lesion and ALN were 0.64 (95% CI 0.23-1.84) and 1.09 (95% CI 0.07-16.53), respectively.

CONCLUSIONS: Our meta-analysis suggested that patients with high primary SUVmax may experience a higher risk for recurrence or a poor progression. Moreover, the SUVmax of [18]F-FDG showed a significant prognostic value in IDC patients.}, } @article {pmid30016315, year = {2018}, author = {Freche, D and Naim-Feil, J and Peled, A and Levit-Binnun, N and Moses, E}, title = {A quantitative physical model of the TMS-induced discharge artifacts in EEG.}, journal = {PLoS computational biology}, volume = {14}, number = {7}, pages = {e1006177}, pmid = {30016315}, issn = {1553-7358}, mesh = {*Artifacts ; Electrodes ; Electroencephalography/*methods ; Evoked Potentials, Motor/physiology ; Humans ; Knee ; *Models, Neurological ; Muscle, Skeletal/physiology ; Phantoms, Imaging ; Reproducibility of Results ; Skin Physiological Phenomena ; Transcranial Magnetic Stimulation/*methods ; }, abstract = {The combination of Transcranial Magnetic Stimulation (TMS) with Electroencephalography (EEG) exposes the brain's global response to localized and abrupt stimulations. However, large electric artifacts are induced in the EEG by the TMS, obscuring crucial stages of the brain's response. Artifact removal is commonly performed by data processing techniques. However, an experimentally verified physical model for the origin and structure of the TMS-induced discharge artifacts, by which these methods can be justified or evaluated, is still lacking. We re-examine the known contribution of the skin in creating the artifacts, and outline a detailed model for the relaxation of the charge accumulated at the electrode-gel-skin interface due to the TMS pulse. We then experimentally validate implications set forth by the model. We find that the artifacts decay like a power law in time rather than the commonly assumed exponential. In fact, the skin creates a power-law decay of order 1 at each electrode, which is turned into a power law of order 2 by the reference electrode. We suggest an artifact removal method based on the model which can be applied from times after the pulse as short as 2 milliseconds onwards to expose the full EEG from the brain. The method can separate the capacitive discharge artifacts from those resulting from cranial muscle activation, demonstrating that the capacitive effect dominates at short times. Overall, our insight into the physical process allows us to accurately access TMS-evoked EEG responses that directly follow the TMS pulse, possibly opening new opportunities in TMS-EEG research.}, } @article {pmid30010547, year = {2019}, author = {Aplin, FP and Singh, D and Santina, CCD and Fridman, GY}, title = {Ionic Direct Current Modulation for Combined Inhibition/Excitation of the Vestibular System.}, journal = {IEEE transactions on bio-medical engineering}, volume = {66}, number = {3}, pages = {775-783}, pmid = {30010547}, issn = {1558-2531}, support = {R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Biomedical Engineering/*instrumentation/methods ; Chinchilla ; Electric Stimulation/*instrumentation/*methods ; Eye Movements/physiology/radiation effects ; Gentamicins ; *Neural Prostheses ; Neurosciences/instrumentation/methods ; Vestibule, Labyrinth/*physiology ; }, abstract = {OBJECTIVE: Prosthetic electrical stimulation delivered to the vestibular nerve could provide therapy for people suffering from bilateral vestibular dysfunction. Common encoding methods use pulse-frequency modulation (PFM) to stimulate the semicircular canals of the vestibular system. We previously showed that delivery of ionic direct current (iDC) can also modulate the vestibular system. In this study, we compare the dynamic range of head velocity encoding from iDC modulation to that of PFM controls.

METHODS: Gentamicin-treated wild-type chinchillas were implanted with microcatheter tubes that delivered ionic current to the left ear vestibular canals and stimulated with steps of anodic/cathodic iDC or PFM. Evoked vestibulo-ocular reflex eye velocity was used to compare PFM and iDC vestibular modulation.

RESULTS: Cathodic iDC steps effectively elicited eye rotations consistent with an increased firing rate of the implanted semicircular canal afferents. Anodic iDC current steps elicited eye rotations in the opposite direction that, when paired with an adapted cathodic offset, increased the dynamic range of eye rotation velocities in comparison to PFM controls.

CONCLUSION: Our results suggest that iDC modulation can effectively modulate the vestibular system across a functional range of rotation vectors and velocities, with a potential benefit over a PFM stimulation paradigm.

SIGNIFICANCE: In conjunction with a safe dc delivery system, iDC modulation could potentially increase the range of simulated head rotation velocities available to neuroelectric vestibular prostheses.}, } @article {pmid30009102, year = {2018}, author = {Katz, H and Jafri, H and Saad, R and Limjoco, T and Tirona, MT}, title = {Colonic Obstruction from an Unusual Cause: A Rare Case of Metastatic Invasive Ductal Carcinoma to the Colon.}, journal = {Cureus}, volume = {10}, number = {5}, pages = {e2588}, pmid = {30009102}, issn = {2168-8184}, abstract = {Colon metastasis from breast cancer is rare. Gastrointestinal (GI) metastasis is more frequently seen in patients with invasive lobular carcinoma of the breast compared to invasive ductal carcinoma; however, the most common sites of metastasis still remain the lymph nodes, lungs, liver, and bones. We describe a 68-year-old female with a remote history of invasive ductal carcinoma of the breast who presented with abdominal pain and a palpable mass. On imaging, she was found to have a colonic obstruction and underwent a right hemicolectomy that proved to be metastatic invasive ductal carcinoma of the breast.}, } @article {pmid30008850, year = {2018}, author = {Yang, L and Wang, XW and Zhu, LP and Wang, HL and Wang, B and Zhao, Q and Wang, XY}, title = {Significance and prognosis of epithelial-cadherin expression in invasive breast carcinoma.}, journal = {Oncology letters}, volume = {16}, number = {2}, pages = {1659-1665}, pmid = {30008850}, issn = {1792-1074}, abstract = {The objective of the present study was to investigate and analyze the epithelial-cadherin (E-cadherin) expression in invasive ductal carcinoma of the breast, and to analyze the associations between the expression and clinicopathological characteristics of lymph node metastasis and the prognosis of breast cancer. The immunohistochemical streptavidin-peroxidase method was used to detect the E-cadherin expression in 30 cases of breast fibroadenoma and in 450 cases of invasive breast cancer, and then the χ[2]test and Kaplan-Meier method were used to analyze the data. The 30 cases of breast fibroadenoma showed positive expression of E-cadherin. Specifically, results found that E-cadherin was highly expressed in 49.04% (77/157) of patients with non-metastatic breast cancer, while low expression was found in 50.96% (80/157). Additionally, E-cadherin was highly expressed in 29.69% (87/293) of patients with lymph node metastasis of breast cancer, with low expression in 70.31% (206/293); these differences were significantly different (χ[2]=16.53; P<0.001). E-cadherin was expressed in 35.48% (22/62), 33.73% (84/249), 63.83% (30/47) and 30.43% (28/92) of patients with luminal A type, luminal B type, human epidermal growth factor receptor-2positive and triple-negative breast cancer (TNBC), respectively. It was found that patients with high expression of E-cadherin had a better prognosis than the low expression group with regards to TNBC, and this result was significantly different (χ[2]=4.48; P=0.034). In conclusion, low E-cadherin expression was associated with lymph node metastasis in invasive breast cancer, and the patients with low expression also had a poor prognosis compared with those in the high expression group. The present results suggested that E-cadherin could be used in a prognostic index for patients with lymph node metastasis and TNBC.}, } @article {pmid30007270, year = {2018}, author = {Haque, W and Verma, V and Hatch, S and Klimberg, VS and Butler, EB and Teh, BS}, title = {Omission of chemotherapy for low-grade, luminal A N1 breast cancer: Patterns of care and clinical outcomes.}, journal = {Breast (Edinburgh, Scotland)}, volume = {41}, number = {}, pages = {67-73}, doi = {10.1016/j.breast.2018.06.014}, pmid = {30007270}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/*drug therapy/mortality/pathology ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology ; Chemotherapy, Adjuvant/*trends ; Databases, Factual ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy/trends ; Middle Aged ; Neoplasm Staging ; Practice Patterns, Physicians'/*trends ; Treatment Outcome ; }, abstract = {PURPOSE: Multiple ongoing randomized studies are assessing the impact of omission of chemotherapy (CT) in low-risk node-positive Luminal A breast. The goal of this investigation was to evaluate trends and practice patterns of adjuvant CT use in Luminal A pT1-3N1 breast cancer, along with determining the clinical benefit from adjuvant CT in this patient population.

METHODS: The National Cancer Data Base was queried (2004-2014) for women with pT1-3N1 luminal A invasive ductal carcinoma receiving adjuvant hormonal therapy (HT). Multivariable logistic regression ascertained factors associated with adjuvant CT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with CT/HT vs. HT alone, while sub-stratifying patients by age.

RESULTS: Of 8548 total patients, 5182 (61%) received CT/HT, while 3366 (39%) received HT alone. A steady rise in omission of adjuvant CT was observed, from 14% (2004-2005) to 41% (2012-2014). A decision not to use CT was more likely in more recent time periods, in older patients, at academic centers, following lumpectomy, and with lower T classification (p < 0.05 for all). CT was associated with higher OS in all patients (p < 0.001) and women ≤50 years old (p = 0.030), but not for ages 51-60 (p = 0.116), 61-70 (p = 0.222), or >70 (p = 0.239).

CONCLUSIONS: Using CT for Luminal A N1 breast cancer is decreasing over time, primarily in older patients and at academic centers. Although CT is still associated with an OS advantage in all patients, subgroup analysis demonstrated no OS benefit in women >50 years of age. These results have implications on the ongoing randomized trials.}, } @article {pmid30001318, year = {2018}, author = {Vasconcellos, AG and Fonseca E Fonseca, BP and Morel, CM}, title = {Revisiting the concept of Innovative Developing Countries (IDCs) for its relevance to health innovation and neglected tropical diseases and for the prevention and control of epidemics.}, journal = {PLoS neglected tropical diseases}, volume = {12}, number = {7}, pages = {e0006469}, pmid = {30001318}, issn = {1935-2735}, mesh = {Africa, Western/epidemiology ; China/epidemiology ; *Developing Countries/statistics & numerical data ; Humans ; Neglected Diseases/*epidemiology/prevention & control ; Public Health ; South America/epidemiology ; Tropical Climate ; *Tropical Medicine ; }, abstract = {INTRODUCTION: Countries have traditionally been split into two major groups: developed or industrialized ("the North") and developing or underdeveloped ("the South"). Several authors and organizations have challenged this classification to recognize countries that have reached an intermediate stage of social and economic development. As proposed by Morel and collaborators in 2005, the concept of Innovative Developing Countries (IDCs) defines a group of nations with impactful scientific programs. Here, IDCs are reexamined by a variety of metrics to highlight their role in health innovation through research and development (R&D) programs on neglected tropical diseases (NTDs) that also positively impact epidemic preparedness.

RESULTS: To address the global changes due to expanding globalization we updated the original indicator of the number of USPTO patents deposited by individual countries per GDP and per capita to the number of international patents applications, related to applicant residence and deposited under the Patent Cooperation Treaty (PCT) per GNI (or GDP) and per capita. A comparison of the originally described ranking of top innovative countries to those in the present study revealed new members that updated the list of IDCs and showed a prominent role now played by China. Analyzing scientific publications in international journals since the introduction of the IDC concept in 2005 we found that IDCs do prioritize Neglected Tropical Diseases (NTDs) as an area of research. Finally we investigated the role of IDCs in two major public health emergencies between 2012 and 2016, the outbreaks of Ebola in West Africa and Zika in South America. An analysis of the co-authorship country networks demonstrated an important role for IDC infrastructure and personnel in the prevention and control of these epidemics.

DISCUSSION AND CONCLUSIONS: Different techniques can be used to evaluate and measure innovative performance of countries. Country rankings published by traditional indexes, such as the Bloomberg Innovation Index (BII) and the Global Innovation Index (GII), only include high income economies among the top 20 performers. This is in sharp contrast to our approach, which identified 8-9 IDCs among the first 25 with China occupying the top position. Through an analysis of the pros and cons of the different methodologies, the IDC concept challenges more conventional approaches to address and estimate the innovative capacity of countries.}, } @article {pmid29993176, year = {2018}, author = {Scholten, M and Suárez, I and Platten, M and Kümmerle, T and Jung, N and Wyen, C and Ernst, A and Horn, C and Burst, V and Suárez, V and Rybniker, J and Fätkenheuer, G and Lehmann, C}, title = {To prescribe, or not to prescribe: decision making in HIV-1 post-exposure prophylaxis.}, journal = {HIV medicine}, volume = {19}, number = {9}, pages = {645-653}, doi = {10.1111/hiv.12645}, pmid = {29993176}, issn = {1468-1293}, mesh = {Adult ; Anti-HIV Agents/*therapeutic use ; Clinical Decision-Making ; Drug Prescriptions/statistics & numerical data ; Female ; HIV Infections/*prevention & control/psychology ; HIV-1/drug effects ; Humans ; Male ; Occupational Exposure ; Post-Exposure Prophylaxis/*methods ; Practice Guidelines as Topic ; Retrospective Studies ; Sex Work/psychology/statistics & numerical data ; Sexual and Gender Minorities/psychology ; Tertiary Healthcare ; }, abstract = {OBJECTIVES: We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines.

METHODS: All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment.

RESULTS: A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61).

CONCLUSIONS: PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.}, } @article {pmid29991088, year = {2018}, author = {Soares, GP and Pereira, AAL and Vilas Boas, MS and Vaisberg, VV and Magalhães, MCF and Linck, RDM and Mano, MS}, title = {Value of Systemic Staging in Asymptomatic Early Breast Cancer.}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {40}, number = {7}, pages = {403-409}, doi = {10.1055/s-0038-1666997}, pmid = {29991088}, issn = {1806-9339}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Asymptomatic Diseases ; Breast Neoplasms/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {OBJECTIVE: Metastases are rare in early breast cancer (EBC), and international guidelines recommend against routine systemic staging for asymptomatic patients. However, imaging exams remain widely employed in the clinical practice. The aim of the present study is to evaluate the value of imaging for systemic staging in EBC.

METHODS:  A retrospective analysis of newly-diagnosed breast cancer (BC) patients was performed. Clinical data including BC subtype, stage, presence of symptoms at diagnosis and instrumental procedures performed for staging were recorded.

RESULTS:  A total of 753 patients were included, with a median age of 57 years. The majority of the patients underwent at least 1 imaging procedure (91%); had invasive ductal carcinoma (83.5%); histological grade 2 (51.4%); stage II (61.8%); and luminal subtype (67.9%). Among the 685 (91%) patients who underwent any radiologic staging, distant metastases (DMs) were detected in 32 (4.7%). In the univariate analyses, stage IIb and pathological lymph node involvement (pN1) showed a statistically significant association with the presence of DMs, versus only a trend for triple negative and human epidermal growth factor receptor 2 (Her2) positive subtype. In an exploratory analysis performed in this same subgroup, when unfavorable biology (triple negative or Her2 positive) was present, patients had a DM rate of 14.4%, one of the highest reported at this stage of the disease.

CONCLUSION:  Early breast cancer has a low prevalence of DM at the initial evaluation, and systemic staging of asymptomatic, unselected patients is not warranted as a routine practice. However, we have identified subgroups of patients to whom a full staging could be indicated.}, } @article {pmid29987603, year = {2018}, author = {Schwartzberg, B and Lewin, J and Abdelatif, O and Bernard, J and Bu-Ali, H and Cawthorn, S and Chen-Seetoo, M and Feldman, S and Govindarajulu, S and Jones, L and Juette, A and Kavia, S and Maganini, R and Pain, S and Shere, M and Shriver, C and Smith, S and Valencia, A and Whitacre, E and Whitney, R}, title = {Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations.}, journal = {Annals of surgical oncology}, volume = {25}, number = {10}, pages = {2958-2964}, pmid = {29987603}, issn = {1534-4681}, support = {BR-002 (NCT01478438)//Novian Health, Inc., Chicago, Illinois/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology/*surgery ; Female ; Humans ; Laser Therapy/*methods ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {BACKGROUND: An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ.

METHODS: Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin-eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns.

RESULTS: In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9-91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2-99.9%).

CONCLUSIONS: Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.}, } @article {pmid29986398, year = {2018}, author = {Hsu, MSH and Harper, C and Gibson, AA and Sweeting, AN and McBride, J and Markovic, TP and Caterson, ID and Byrne, NM and Sainsbury, A and Seimon, RV}, title = {Recruitment Strategies for a Randomised Controlled Trial Comparing Fast Versus Slow Weight Loss in Postmenopausal Women with Obesity-The TEMPO Diet Trial.}, journal = {Healthcare (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {29986398}, issn = {2227-9032}, abstract = {Current research around effective recruitment strategies for clinical trials of dietary obesity treatments have largely focused on younger adults, and thus may not be applicable to older populations. The TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity) is a randomised controlled trial comparing the long-term effects of fast versus slow weight loss on body composition and cardio-metabolic health in postmenopausal women with obesity. This paper addresses the recruitment strategies used to enrol participants into this trial and evaluates their relative effectiveness. 101 post-menopausal women aged 45[-]65 years, with a body mass index of 30[-]40 kg/m[2] were recruited and randomised to either fast or slow weight loss. Multiple strategies were used to recruit participants. The total time cost (labour) and monetary cost per randomised participant from each recruitment strategy was estimated, with lower values indicating greater cost-effectiveness and higher values indicating poorer cost-effectiveness. The most cost-effective recruitment strategy was word of mouth, followed (at equal second place) by free publicity on TV and radio, and printed advertorials, albeit these avenues only yielded 26/101 participants. Intermediate cost-effective recruitment strategies were flyer distribution at community events, hospitals and a local tertiary education campus, internet-based strategies, and clinical trial databases and intranets, which recruited a further 40/101 participants. The least cost-effective recruitment strategy was flyer distribution to local health service centres and residential mailboxes, and referrals from healthcare professionals were not effective. Recruiting for clinical trials involving postmenopausal women could benefit from a combination of recruitment strategies, with an emphasis on word of mouth and free publicity via radio, TV, and print media, as well as strategic placement of flyers, supplemented with internet-based strategies, databases and intranets if a greater yield of participants is needed.}, } @article {pmid29985403, year = {2018}, author = {Painter, HJ and Chung, NC and Sebastian, A and Albert, I and Storey, JD and Llinás, M}, title = {Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {2656}, pmid = {29985403}, issn = {2041-1723}, support = {R21 AI133379/AI/NIAID NIH HHS/United States ; }, mesh = {Erythrocytes/parasitology ; Gene Expression Profiling ; Gene Ontology ; Genes, Protozoan/*genetics ; Genome, Protozoan/*genetics ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*genetics/physiology ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; *Transcription, Genetic ; }, abstract = {Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.}, } @article {pmid29985074, year = {2018}, author = {Autenshlyus, A and Arkhipov, S and Mikhailova, E and Arkhipova, V and Varaksin, N}, title = {VEGF-R2 and TNF-R1 expression and cytokine production by samples of mammary adenocarcinomas and correlations with histopathological parameters of these malignant tumors.}, journal = {International journal of immunopathology and pharmacology}, volume = {32}, number = {}, pages = {2058738418787990}, pmid = {29985074}, issn = {2058-7384}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cytokines/*metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Receptors, Tumor Necrosis Factor, Type I/*metabolism ; Vascular Endothelial Growth Factor Receptor-2/*metabolism ; }, abstract = {Currently, the role of cytokines in the tumor progression, including breast cancer, is universally recognized. At the same time, there are still many questions concerning the role of individual cytokines and receptors for cytokines in various morphogenetic processes underlying the tumor progression. The objective of this work was to study cytokine production and vascular endothelial growth factor (VEGF)-R2 and VEGF-R1 expression by mammary adenocarcinoma (MAC) and the correlations with histopathological parameters of malignant tumors. The object of the study was cultured tumor biopsy samples from 47 women aged 43-75 years with invasive ductal carcinoma, which was classified as grade II-III adenocarcinoma. It was shown that the cytokine profiles of the supernatants of MAC samples from patients differ greatly. A correlation between the levels of VEGF-R2 and tumor necrosis factor (TNF)-R1 expression was observed. Correlations were also revealed during analysis of the relations of histopathological MAC indicators with KVEGF-R2/VEGF-A and KTNF-R1/TNF-α coefficients, which are equal, respectively, to the ratio of expression values of receptors VEGF-R2 and TNF-R1 to the concentrations of the relevant cytokines (VEGF-A and TNF-α) in the culture supernatants of the same MAC samples. A direct correlation was identified between KVEGF-R/VEGF-A and some histopathological MAC characteristics: proportion of cells undergoing mitosis or pathological mitosis in MAC and poorly differentiated cells. KVEGF-R2/VEGF-A directly correlated with the concentration in supernatant interleukin (IL)-18 and interferon (IFN)-γ. KTNF-R1/TNF-α was inversely correlated with the concentration in supernatant of IL-1Ra, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The data obtained show that the high-level production of IL-18 and IL-1β by MAC, overexpression of VEGF-R2 in tumor (at relatively low VEGF-A production), and the high level of IFN-γ production are attributed factors contributing to the formation of a population of low-grade cells in the tumor. The factors regulating the population of moderately differentiated cells in the tumor are referred to as IL-1Ra, IL-8, and GM-CSF.}, } @article {pmid29984255, year = {2018}, author = {Bongomin, F and Chelangat, M and Eriatu, A and Chan Onen, B and Cheputyo, P and Godmercy, SA and Ekuk, E and Idony, F and Henry Obol, J}, title = {Prevalence and Factors Associated with Contraceptive Use among HIV-Infected Women of Reproductive Age Attending Infectious Disease Clinic at Gulu Regional Referral Hospital, Northern Uganda.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {9680514}, pmid = {29984255}, issn = {2314-6141}, mesh = {Adolescent ; Adult ; Contraception Behavior ; *Contraceptive Agents ; Cross-Sectional Studies ; Female ; *HIV Infections ; Humans ; Middle Aged ; Pregnancy ; Prevalence ; Referral and Consultation ; Uganda ; Young Adult ; }, abstract = {BACKGROUND: Reproductive planning by HIV-infected women is essential, as it helps to prevent transmission of HIV to their unborn babies. Integrating contraceptive services to routine HIV care significantly increases the use of modern contraceptive methods, thus reducing vertical transmission of HIV.

OBJECTIVES: To determine the prevalence and factors associated with contraceptive use among HIV-infected women attending Infectious Disease Clinic (IDC) at Gulu Regional Referral Hospital (GRRH) in Northern Uganda.

METHODOLOGY: A hospital-based cross-sectional study was performed. We used simple random sampling to recruit HIV-infected women receiving routine care from IDC, GRRH, into our study. Sample size was estimated using modified Kish-Leslie formula and semistructured questionnaire was used for data collection. Data was entered into EpiData version 3.1 and analysed using Stata v11.0. We used logistic regression model to assess the associations and any factor with p≤0.05 was considered statistically significant.

RESULTS: The prevalence of contraceptive use was found to be 36% (95% CI 31 - 40%). Factors which promoted contraceptive use were as follows: being married (aOR=2.68, 95% CI 1.54-4.65, p<0.001) and monthly income of $35 -250 (aOR= 2.38, 95% CI: 1.39- 4.09, p=0.002). Factors that hindered contraceptive use were having no child (nulliparity) (aOR= 0.16; 95% CI: 0.05-0.49; p=0.002) and age range of 31-49 years (aOR= 0.53; 95% CI: 0.33 - 0.84; p=0.007).

CONCLUSION: In this study, just over a third of sexually active HIV-infected women reported use of modern contraceptives. This is a low level of usage and, therefore, clinicians and stakeholders should sensitise HIV-infected women on the importance of contraceptive use in the fight against HIV/AIDS and encourage them to use contraceptives to avoid vertical transmission of HIV through unintended pregnancy.}, } @article {pmid29983888, year = {2018}, author = {Kaymak, A and Sayols, S and Papadopoulou, T and Richly, H}, title = {Role for the transcriptional activator ZRF1 in early metastatic events in breast cancer progression and endocrine resistance.}, journal = {Oncotarget}, volume = {9}, number = {47}, pages = {28666-28690}, pmid = {29983888}, issn = {1949-2553}, abstract = {Breast cancer is one of the most common malignancies among women which is often treated with hormone therapy and chemotherapy. Despite the improvements in detection and treatment of breast cancer, the vast majority of breast cancer patients are diagnosed with metastatic disease either at the beginning of the disease or later during treatment. Still, the molecular mechanisms causing a therapy resistant metastatic breast cancer are still elusive. In the present study we addressed the function of the transcriptional activator ZRF1 during breast cancer progression. We provide evidence that ZRF1 plays an essential role for the early metastatic events in vitro and acts like a tumor suppressor protein during the progression of breast invasive ductal carcinoma into a more advanced stage. Hence, depletion of ZRF1 results in the acquisition of metastatic behavior by facilitating the initiation of the metastatic cascade, notably for cell adhesion, migration and invasion. Furthermore absence of ZRF1 provokes endocrine resistance via misregulation of cell death and cell survival related pathways. Taken together, we have identified ZRF1 as an important regulator of breast cancer progression that holds the potential to be explored for new treatment strategies in the future.}, } @article {pmid29981615, year = {2018}, author = {Du, R and Zhang, H and Shu, W and Chen, B and Li, Y and Zhang, X and Wu, X and Wang, Z}, title = {Correlation between Ki-67 Expression and Hemodynamics of Contrast-Enhanced Ultrasound in Patients with Breast Infiltrative Ductal Carcinoma.}, journal = {The American surgeon}, volume = {84}, number = {6}, pages = {856-861}, pmid = {29981615}, issn = {1555-9823}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*diagnostic imaging/*metabolism/physiopathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*metabolism/physiopathology ; Cohort Studies ; Contrast Media ; Female ; Hemodynamics ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Regional Blood Flow ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {Breast cancer causes great threats to public health worldwide. The aim of this study was to investigate the correlation between Ki-67 expression and the hemodynamics of contrast-enhanced ultrasound (CEUS) in patients with infiltrative ductal carcinoma (IDC). CEUS was performed on 109 masses in 85 IDC cases before resection. Based on the immunohistochemical staining on the antigen Ki-67, the masses were divided into negative group, weakly positive group, positive group, and strong-positive group. Significant statistical differences were noticed in time to peak, arrive intensity, and peak intensity in the positive groups compared with the negative group. Compared with the positive groups, the negative group showed significant statistical differences in arrive intensity and peak intensity. The antigen Ki-67 was positively correlated with arrived intensity, intensity changes, and rising curve's slope. In contrast, it was negatively correlated with arrived time, time to peak, and continuous time. The hemodynamic parameters of CEUS were correlated with the expression of antigen Ki-67. On this basis, Ki-67 is an effective supplement to the diagnosis of IDC.}, } @article {pmid29974289, year = {2018}, author = {Nikolić, D and Granić, M and Ivanović, N and Zdravković, D and Nikolić, A and Stanimirović, V and Zdravković, M and Dikić, S and Nikolić, M and Djordjević, M}, title = {Breast cancer and its impact in male transsexuals.}, journal = {Breast cancer research and treatment}, volume = {171}, number = {3}, pages = {565-569}, doi = {10.1007/s10549-018-4875-y}, pmid = {29974289}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/diagnostic imaging/epidemiology/*physiopathology ; Depression/epidemiology/*physiopathology ; Female ; Gender Identity ; Hormones/metabolism ; Humans ; Male ; Mammography ; Sex Reassignment Surgery ; Sexual Behavior ; Transgender Persons ; Treatment Outcome ; }, abstract = {INTRODUCTION: Lesbian, gay, and bisexuals have unique healthcare needs. Breast cancer is leading cancer in women, worldwide, accounting for 25% of all cases. Annual incidence rates increased significantly in all countries and age groups. The occurrence of breast cancer is rare in transgender population. As they have very limited access to medical care, it is much less likely to pursue breast cancer screening than in other individuals not identified as transgender.

Up to date, only 13 cases of the breast cancer transsexuals (female to male) have been reported in six published papers worldwide. Histological examination of the breast tumor in female-to-male transgender showed progesterone/estrogen-positive invasive ductal carcinoma.

DISCUSSION: Gender identity describes a person's inherent sense of being a woman, man, or of neither gender, whereas sexual orientation refers to how people identify their physical and emotional attraction to others. Gender reassignment surgery, as series of complex surgical genital and non-genital procedures, is recognized as the most effective treatment for patients with gender dysphoria. The two main principles of hormone therapy for transgender patients are to reduce endogenous hormone levels and their associated sex characteristics and replace them with hormones of the preferred sex. Breast cancer infrequently occurs in transgender patients. Even breast core biopsies can be difficult for interpreting after changes in breast tissue in female-to-male transsexuals following gender reassignment.

CONCLUSION: Reviewing the literature, so many different data concerning probability of breast cancer in sexual minority can be found. Breast cancer screening program should be offered to all transgender individuals according to national guidelines. Very important is to take into consideration a transgender person's natal and surgical anatomy, unique clinical concerns for depression and anxiety, risk of suicide together with risk factors including experiences of harassment or physical or sexual violence, low education level, and unemployment. Understanding the need for mammography in these often marginalized groups is very important in addressing breast cancer disparities despite differences in insurance coverage in some countries and greater concern for the cancer of the breast in residual breast tissue. The best screening rule, ever, for breast cancer in male transsexuals and other similar population should be, besides surgical history and hormonal status, "Screen Now, Screen Regularly and Screen What You Have."}, } @article {pmid29973382, year = {2018}, author = {Bayindir-Buchhalter, I and Wolff, G and Lerch, S and Sijmonsma, T and Schuster, M and Gronych, J and Billeter, AT and Babaei, R and Krunic, D and Ketscher, L and Spielmann, N and Hrabe de Angelis, M and Ruas, JL and Müller-Stich, BP and Heikenwalder, M and Lichter, P and Herzig, S and Vegiopoulos, A}, title = {Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.}, journal = {EMBO molecular medicine}, volume = {10}, number = {8}, pages = {}, pmid = {29973382}, issn = {1757-4684}, mesh = {Adipocytes/*drug effects/metabolism ; Animals ; Diabetes Mellitus, Type 2/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Male ; Mice ; Molecular Targeted Therapy ; PPAR gamma/metabolism ; Rosiglitazone/*therapeutic use ; Sex Factors ; Stem Cells/drug effects/metabolism ; Thermogenesis ; Transcription Factors/biosynthesis/*metabolism ; Transcription, Genetic/drug effects ; Uncoupling Protein 1/biosynthesis ; }, abstract = {Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.}, } @article {pmid29973218, year = {2018}, author = {Zubeldia-Plazaola, A and Recalde-Percaz, L and Moragas, N and Alcaraz, M and Chen, X and Mancino, M and Fernández-Nogueira, P and Prats de Puig, M and Guzman, F and Noguera-Castells, A and López-Plana, A and Enreig, E and Carbó, N and Almendro, V and Gascón, P and Bragado, P and Fuster, G}, title = {Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis.}, journal = {Breast cancer research : BCR}, volume = {20}, number = {1}, pages = {65}, pmid = {29973218}, issn = {1465-542X}, mesh = {Animals ; Apoptosis/genetics ; Biomarkers, Tumor/*blood/genetics ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*blood/genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Glucocorticoids/*blood ; Heterografts ; Humans ; Laminin/genetics ; Mice ; Myoepithelioma/blood/genetics/pathology ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells.

METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples.

RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS.

CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.}, } @article {pmid29973211, year = {2018}, author = {Ambrosini, GL and Solis-Trapala, I and Ahern, AL and Fuller, NR and Holzapfel, C and Hauner, H and Caterson, ID and Jebb, SA}, title = {Greater improvements in diet quality among overweight participants following a group-based commercial weight loss programme than those receiving support to lose weight in primary care.}, journal = {Nutrition journal}, volume = {17}, number = {1}, pages = {64}, pmid = {29973211}, issn = {1475-2891}, support = {G0501294/MRC_/Medical Research Council/United Kingdom ; MC_U105960389/MRC_/Medical Research Council/United Kingdom ; MC_UU_12015/4/MRC_/Medical Research Council/United Kingdom ; U105960389/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Australia ; Behavior Therapy ; Body Mass Index ; Diet, Reducing ; Dietary Fiber/administration & dosage ; Dietary Proteins/administration & dosage ; Energy Intake ; Female ; Humans ; Male ; Middle Aged ; Overweight/*therapy ; *Primary Health Care ; United Kingdom ; Weight Loss ; *Weight Reduction Programs ; }, abstract = {BACKGROUND: Relatively little is known about dietary changes and their relationships with weight change during behavioural weight loss interventions. In a secondary analysis of data from a multicentre RCT, we investigated whether greater improvements in diet would be achieved by overweight adults following a 12 month group-based commercial weight loss programme (CP) than those receiving standard care (SC) in primary practice, and if these dietary changes were associated with greater weight loss.

METHODS: Adults with a BMI 27-35 kg/m[2] and >1 risk factor for obesity-related disorders were recruited in study centres in Australia and the UK during 2007-2008. Dietary intake and body weight were measured at baseline, 6 and 12 months. Linear mixed effects models compared mean changes in dietary macronutrient intake, fibre density and energy density over time between groups, and their relationships with weight loss.

RESULTS: The CP group demonstrated greater mean weight loss than the SC group at 6 months (3.3 kg, 95% CI: 2.2, 4.4) and 12 months (3.3 kg, 95% CI: 2.1, 4.5). Diet quality improved in both intervention groups at 6 and 12 months. However, the CP group (n = 228) achieved significantly greater mean reductions in energy intake (mean difference; 95% CI: - 503 kJ/d; - 913, - 93), dietary energy density (- 0.48 MJ/g; - 0.81, - 0.16), total fat (- 6.9 g/d; - 11.9, - 1.8), saturated fat (- 3.3 g/d; - 5.4, - 1.1), and significantly greater mean increases in fibre density (0.30 g/MJ; 0.15, 0.44) at 6 months than the SC group (n = 239). Similar differences persisted at 12 months and the CP group showed greater mean increases in protein density (0.65 g/MJ). In both groups, weight loss was associated with increased fibre density (0.68 kg per g/MJ, 95% CI: 0.08, 1.27) and protein density (0.26 kg per g/MJ, 95% CI: 0.10, 0.41).

CONCLUSIONS: Following a group-based commercial program led to greater improvements in diet quality than standard care. Increases in dietary protein and fibre density were independently associated with weight loss in both behavioural weight loss interventions. Greater increases in protein and fibre density in the commercial program likely contributed to their greater weight loss.

TRIAL REGISTRATION: ISRCTN: ISRCTN85485463 Registered 03/08/2007 Retrospectively Registered.}, } @article {pmid31949729, year = {2018}, author = {Yue, X and Han, Z and Zhang, L and Li, J and Gong, X}, title = {Aberrant expression of ALDH1, MMP9, Integrin αvβ3, and KiSS-1 in invasive ductal carcinoma and their clinical significance.}, journal = {International journal of clinical and experimental pathology}, volume = {11}, number = {7}, pages = {3511-3522}, pmid = {31949729}, issn = {1936-2625}, abstract = {BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), matrix metalloproteinase 9 (MMP9, known as a matrilysin), Integrin αvβ3 (known as a biomarker of cell-matrix adhesion) and KiSS-1 (suppressor gene of tumor metastasis) are all related to cancer invasion and metastasis in many cancers. The purpose of this study was to investigate the expression of ALDH1, MMP9, Integrin αvβ3, and KiSS-1 in invasive ductal carcinoma (IDC), and their respective associations with clinical characteristics and survival in IDC.

METHODS: Immunohistochemical staining was used to detect the expression of ALDH1, MMP9, Integrin αvβ3, and KiSS-1 in 227 whole IDC tissue specimens. Patients' clinical and demographic data were both collected.

RESULTS: The expression of ALDH1, MMP9, and Integrin αvβ3 were significantly higher in IDC tissues than in the control tissues. The positive expressions of ALDH1, MMP9, and Integrin αvβ3 were positively associated with tumor grades, lymph node metastasis (LNM), tumor stages, and tumor node metastasis (TNM) stages, and inversely with overall survival (OS) and recurrence-free survival (RFS). Positive expression of KiSS-1 was negatively associated with tumor grades, LNM, tumor stages, and TNM stages, but positively with OS and RFS. A multivariate analysis demonstrated that the positive expression of ALDH1, MMP9, Integrin αvβ3, KiSS-1, ER, and HER-2, as well as TNM stages were independent prognostic factors for OS and RFS in IDC.

CONCLUSIONS: The expression of ALDH1, MMP9, Integrin αvβ3, and KiSS-11 should represent promising biomarkers in predicting metastasis and prognosis, as well as being potential therapeutic targets for IDC.}, } @article {pmid29959577, year = {2019}, author = {Holtmaat, K and van der Spek, N and Lissenberg-Witte, BI and Cuijpers, P and Verdonck-de Leeuw, IM}, title = {Positive mental health among cancer survivors: overlap in psychological well-being, personal meaning, and posttraumatic growth.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {2}, pages = {443-450}, pmid = {29959577}, issn = {1433-7339}, support = {4864//KWF Kankerbestrijding/ ; }, mesh = {Cancer Survivors/*psychology ; Female ; Humans ; Male ; Mental Health/*trends ; Middle Aged ; Neoplasms/mortality/*psychology ; Patient Reported Outcome Measures ; *Posttraumatic Growth, Psychological ; }, abstract = {PURPOSE: Positive mental health involves theoretical constructs like psychological well-being, personal meaning, and posttraumatic growth. This study aims to provide empirical insight into possible overlap between these constructs in cancer survivors.

METHODS: Within the context of a randomized controlled trial, 170 cancer survivors completed the patient-reported outcome measures (PROMs) Ryff's Scales of Psychological Well-Being (SPWB), Personal Meaning Profile (PMP), and Posttraumatic Growth Inventory (PTGI). Exploratory factor analysis (EFA) on the subscales of these PROMs, as well as structural equation modeling (SEM), was used to explore overlap in these three constructs.

RESULTS: The EFA resulted in a three-factor solution with an insufficient model fit. SEM led to a model with a high estimated correlation (0.87) between SPWB and PMP and lower estimated correlations with PTGI (respectively 0.38 and 0.47). Furthermore, the estimated correlation between the subscales relation with God (PMP) and spiritual change (PTGI) was high (0.92). This model had adequate fit indices (χ[2](93) = 144, p = .001, RMSEA = 0.059, CFI = 0.965, TLI = 0.955, SRMR = 0.061).

CONCLUSIONS: The constructs psychological well-being and personal meaning overlap to a large extent in cancer survivors. Posttraumatic growth can be seen as a separate construct, as well as religiosity. These findings facilitate researchers to select the appropriate PROM(s) when testing the effect of a psychosocial intervention on positive mental health in cancer survivors.

RELEVANCE: An increasing number of psychosocial intervention trials for cancer survivors use positive mental health outcomes. These constructs are often multifaceted and overlapping. Knowledge of this overlap is important in designing trials, in order to avoid the pitfalls of multiple testing and finding artificially strengthened associations.

NETHERLANDS TRIAL REGISTER: NTR3571.}, } @article {pmid29959495, year = {2018}, author = {Eck, DL and Nguyen, DC and Barnes, LL and Jansen, DA}, title = {Treatment of Breast Animation Deformity in Implant-Based Reconstruction with Selective Nerve Ablation.}, journal = {Aesthetic plastic surgery}, volume = {42}, number = {6}, pages = {1472-1475}, doi = {10.1007/s00266-018-1184-0}, pmid = {29959495}, issn = {1432-5241}, mesh = {Adult ; Breast Implantation/*adverse effects/methods ; *Breast Implants ; Breast Neoplasms/pathology/*surgery ; Denervation/methods ; Esthetics ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/adverse effects/methods ; Mastectomy/methods ; Pectoralis Muscles/*innervation/*surgery ; Peripheral Nerves/*surgery ; Prosthesis Failure ; Reoperation/methods ; Treatment Outcome ; }, abstract = {Breast animation deformity is a known complication of subpectoral implant placement that is usually corrected by repositioning the implant to the prepectoral position. Other less common treatment options include performing the muscle splitting biplanar technique, triple plane technique, neuromodulator injections, and secondary neurotomies via transection of the pectoral muscle. We report a patient with animation deformity successfully treated with direct identification and ablation of the medial and lateral pectoral nerves using selective bipolar electrocautery. The patient is a woman with a history of invasive ductal carcinoma who underwent bilateral mastectomy and breast reconstruction with subpectoral implant placement and autologous fat grafting. Within 1 year of her breast reconstruction, she developed hyperactive pectoralis muscle contraction with resulting distortion of both breasts. Given the disadvantages of repositioning the implant to the prepectoral position and transecting the pectoralis muscles via secondary neurotomy, we chose to directly identify and selectively ablate distal branches of the medial and lateral pectoral nerves. This offers a novel technique for correcting breast animation deformity without transecting the pectoralis muscles, causing muscle atrophy, and preserving the subpectoral implant position.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .}, } @article {pmid29956094, year = {2018}, author = {Graff-Baker, AN and Orozco, JIJ and Marzese, DM and Salomon, MP and Hoon, DSB and Goldfarb, M}, title = {Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.}, journal = {Annals of surgical oncology}, volume = {25}, number = {10}, pages = {3082-3087}, doi = {10.1245/s10434-018-6582-7}, pmid = {29956094}, issn = {1534-4681}, mesh = {Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Carcinoma, Lobular/genetics/pathology/surgery ; DNA Methylation ; *Epigenomics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Middle Aged ; Neoplasms, Second Primary/*genetics/pathology/surgery ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy.

METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs.

RESULTS: Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes.

CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.}, } @article {pmid29955655, year = {2018}, author = {Doniger, GM and Beeri, MS and Bahar-Fuchs, A and Gottlieb, A and Tkachov, A and Kenan, H and Livny, A and Bahat, Y and Sharon, H and Ben-Gal, O and Cohen, M and Zeilig, G and Plotnik, M}, title = {Virtual reality-based cognitive-motor training for middle-aged adults at high Alzheimer's disease risk: A randomized controlled trial.}, journal = {Alzheimer's & dementia (New York, N. Y.)}, volume = {4}, number = {}, pages = {118-129}, pmid = {29955655}, issn = {2352-8737}, abstract = {INTRODUCTION: Ubiquity of Alzheimer's disease (AD) coupled with relatively ineffectual pharmacologic treatments has spurred interest in nonpharmacologic lifestyle interventions for prevention or risk reduction. However, evidence of neuroplasticity notwithstanding, there are few scientifically rigorous, ecologically relevant brain training studies focused on building cognitive reserve in middle age to protect against cognitive decline. This pilot study will examine the ability of virtual reality (VR) cognitive training to improve cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD risk due to parental history.

METHODS: The design is an assessor-blind, parallel group, randomized controlled trial of VR cognitive-motor training in middle-aged adults with AD family history. The experimental group will be trained with adaptive "real-world" VR tasks targeting sustained and selective attention, working memory, covert rule deduction, and planning, while walking on a treadmill. One active control group will perform the VR tasks without treadmill walking; another will walk on a treadmill while watching scientific documentaries (nonspecific cognitive stimulation). A passive (waitlist) control group will not receive training. Training sessions will be 45 minutes, twice/week for 12 weeks. Primary outcomes are global cognition and CBF (from arterial spin labeling [ASL]) at baseline, immediately after training (training gain), and 3 months post-training (maintenance gain). We aim to recruit 125 participants, including 20 passive controls and 35 in the other groups.

DISCUSSION: Current pharmacologic therapies are for symptomatic AD patients, whereas nonpharmacologic training is administrable before symptom onset. Emerging evidence suggests that cognitive training improves cognitive function. However, a more ecologically valid cognitive-motor VR setting that better mimics complex daily activities may augment transfer of trained skills. VR training has benefited clinical cohorts, but benefit in asymptomatic high-risk individuals is unknown. If effective, this trial may help define a prophylactic regimen for AD, adaptable for home-based application in high-risk individuals.}, } @article {pmid29954760, year = {2018}, author = {Kase, AM and Menke, D and Tan, W}, title = {Breast cancer metastasis to the bladder: a literature review.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29954760}, issn = {1757-790X}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/drug therapy/*pathology ; *Cancer Survivors ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Cystoscopy ; Estradiol/*analogs & derivatives/therapeutic use ; Fatal Outcome ; Female ; Fulvestrant ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Urinary Bladder Neoplasms/complications/diagnosis/drug therapy/*secondary ; Urinary Bladder, Overactive/*etiology ; }, abstract = {Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.}, } @article {pmid29951883, year = {2018}, author = {Finet, JE and Wiggers, GA}, title = {Pharmacologic Management of Cancer Therapeutics-Induced Cardiomyopathy in Adult Cancer Survivors.}, journal = {Current heart failure reports}, volume = {15}, number = {4}, pages = {270-279}, pmid = {29951883}, issn = {1546-9549}, mesh = {Adult ; *Cancer Survivors ; *Cardiomyopathies/chemically induced/drug therapy/epidemiology ; Cardiovascular Agents/*therapeutic use ; Comorbidity ; Global Health ; Heart Failure/*drug therapy/epidemiology ; Humans ; Neoplasms/*drug therapy/epidemiology ; }, abstract = {PURPOSE OF REVIEW: The number of cancer survivors is exponentially increasing worldwide, due to both advances in cancer detection and treatment strategies, as well as the aging and growth of the population. This decrease in cancer mortality has brought forth a concurrent increase of non-ischemic (toxic) dilated cardiomyopathy in the survivor population, also known as cancer therapeutics-induced cardiomyopathy (CTIC). The optimal pharmacological management for this condition is still elusive, and hence, the focus of this work.

RECENT FINDINGS: Our review of the literature did not identify any prospective randomized clinical trial of CTIC in adult cancer survivors, neither published nor in progress. However, available data seem to suggest that, when managed with standard guideline-derived medical therapy, the outcomes of CTIC are comparable to that of idiopathic dilated cardiomyopathy (IDC). Nonetheless, the evidence behind this strategy is inadequate. Until new information becomes available, pharmacological management of CTIC must parallel that of IDC. However, implementation of such may be hindered by other cancer therapeutics-induced comorbidities and conditioned by the particular effects of heart failure pharmacotherapy on cancer outcomes. This work succinctly reviews these three areas, in the context of adult cancer survivors.}, } @article {pmid29946290, year = {2018}, author = {Morgulev, E and Galily, Y}, title = {Choking or Delivering Under Pressure? The Case of Elimination Games in NBA Playoffs.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {979}, pmid = {29946290}, issn = {1664-1078}, abstract = {Neoclassical economic theories foretell that individuals exert the most effort, and consequently produce their best performances, when the net returns to effort are highest. We scanned through 33 NBA seasons and analyzed 1930 playoffs games in order to test this prediction. Analysis of win probabilities in games where one of the two teams faces elimination from the playoffs, demonstrated that the threat of severe losses didn't lead to elevated level of performance. While previous studies analyzed mainly single-level performance in a stable environment, our results shed light on collective performance in a dynamic setting. These findings can be applicable to other realms as we suggest that managers should refrain from deliberate building of high-pressure environments with hopes of achieving performance enhancement effect among their groups.}, } @article {pmid29946183, year = {2018}, author = {Krings, G and Chen, YY}, title = {Genomic profiling of metaplastic breast carcinomas reveals genetic heterogeneity and relationship to ductal carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {31}, number = {11}, pages = {1661-1674}, doi = {10.1038/s41379-018-0081-z}, pmid = {29946183}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Gene Expression Profiling ; *Genetic Heterogeneity ; Humans ; Metaplasia ; Middle Aged ; Transcriptome ; Triple Negative Breast Neoplasms/*genetics/pathology ; }, abstract = {Metaplastic breast carcinomas comprise a histologically heterogenous group of tumors. Although most are triple (estrogen/progesterone receptor, HER2) negative, these rare tumors are clinicopathologically distinct from other triple negative carcinomas and may be aggressive with worse chemotherapy responses. On the other hand, metaplastic carcinomas are histologically diverse, which is reflected in gene expression differences among subtypes. Whether metaplastic carcinomas are genetically distinct from other triple negative cancers and whether genetic differences underlie histologic subtypes remains poorly understood. We sequenced 408 cancer-related genes in 28 metaplastic carcinomas, including chondroid matrix-producing carcinomas (n = 10), spindle cell carcinomas (n = 5), and carcinomas with squamous (n = 5), mixed spindle/squamous (n = 5), and mixed metaplastic (n = 3) differentiation. Metaplastic carcinomas were highly enriched for PIK3CA/PIK3R1 (61%) and Ras-Map kinase (25%) pathway aberrations compared to other triple negative carcinomas (TCGA dataset 14%, p < 0.001 and 7%, p = 0.005, respectively) and harbored a high frequency of TP53 (64%) and TERT promoter (25%) mutations, but this varied among subtypes. Chondroid-matrix producing carcinomas lacked PI-3 kinase and Ras-Map kinase aberrations and TERT promoter mutations, compared to 100%, 39%, and 39% of non-matrix-producing tumors, respectively. TERT promoter mutations were enriched (47%) in spindle cell carcinomas and tumors with squamous or spindle/squamous differentiation. Spindle cell carcinomas lacked TP53 mutations, in contrast to other subtypes (78%, p = 0.003). Separate analysis of paired ductal carcinoma in situ and metaplastic carcinoma revealed shared clonality in all cases (n = 8). Activating PI-3 kinase and Ras pathway mutations were early events, and inactivating mutations in tumor suppressors including RB1, CDKN2A, and TP53 were associated with invasion in individual cases. Metaplastic components of two tumors showed genetic progression from separately sequenced paired invasive ductal carcinoma. The findings suggest that metaplastic carcinomas are genetically distinct from other triple negative breast cancers and highlight genetic heterogeneity that broadly correlates with histologic subtype. Heterologous elements progress from associated ductal carcinoma.}, } @article {pmid29943843, year = {2018}, author = {Esmaeili, SA and Mahmoudi, M and Rezaieyazdi, Z and Sahebari, M and Tabasi, N and Sahebkar, A and Rastin, M}, title = {Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {9}, pages = {7865-7872}, doi = {10.1002/jcb.27203}, pmid = {29943843}, issn = {1097-4644}, mesh = {Adult ; Case-Control Studies ; Cell Culture Techniques ; Cells, Cultured ; Cytokines/genetics/metabolism ; Dendritic Cells/*cytology/immunology/microbiology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism ; Interleukin-4/pharmacology ; Lactobacillus delbrueckii/immunology/*physiology ; Lacticaseibacillus rhamnosus/immunology/*physiology ; Lupus Erythematosus, Systemic/immunology/*microbiology ; Male ; Monocytes/*cytology/drug effects/immunology/microbiology ; Probiotics ; }, abstract = {Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM-CSF and IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase (IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis.}, } @article {pmid29941818, year = {2018}, author = {Serra-Majem, L and Raposo, A and Aranceta-Bartrina, J and Varela-Moreiras, G and Logue, C and Laviada, H and Socolovsky, S and Pérez-Rodrigo, C and Aldrete-Velasco, JA and Meneses Sierra, E and López-García, R and Ortiz-Andrellucchi, A and Gómez-Candela, C and Abreu, R and Alexanderson, E and Álvarez-Álvarez, RJ and Álvarez Falcón, AL and Anadón, A and Bellisle, F and Beristain-Navarrete, IA and Blasco Redondo, R and Bochicchio, T and Camolas, J and Cardini, FG and Carocho, M and Costa, MDC and Drewnowski, A and Durán, S and Faundes, V and Fernández-Condori, R and García-Luna, PP and Garnica, JC and González-Gross, M and La Vecchia, C and Leis, R and López-Sobaler, AM and Madero, MA and Marcos, A and Mariscal Ramírez, LA and Martyn, DM and Mistura, L and Moreno Rojas, R and Moreno Villares, JM and Niño-Cruz, JA and Oliveira, MBPP and Palacios Gil-Antuñano, N and Pérez-Castells, L and Ribas-Barba, L and Rincón Pedrero, R and Riobó, P and Rivera Medina, J and Tinoco de Faria, C and Valdés-Ramos, R and Vasco, E and Wac, SN and Wakida, G and Wanden-Berghe, C and Xóchihua Díaz, L and Zúñiga-Guajardo, S and Pyrogianni, V and Cunha Velho de Sousa, S}, title = {Ibero[-]American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages.}, journal = {Nutrients}, volume = {10}, number = {7}, pages = {}, pmid = {29941818}, issn = {2072-6643}, mesh = {Animals ; Beverages/adverse effects/*standards ; Blood Glucose/metabolism ; Consensus ; Consumer Product Safety/*standards ; Diabetes Mellitus/blood/epidemiology/therapy ; Energy Intake ; Food/adverse effects/*standards ; Food Labeling/standards ; *Food Safety ; Humans ; Non-Nutritive Sweeteners/adverse effects/*standards ; Nutritive Sweeteners/adverse effects/*standards ; *Nutritive Value ; Obesity/epidemiology/physiopathology/therapy ; Recommended Dietary Allowances ; Risk Assessment ; Weight Loss ; }, abstract = {International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2[-]4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable.}, } @article {pmid29941485, year = {2018}, author = {Nagle, AM and Levine, KM and Tasdemir, N and Scott, JA and Burlbaugh, K and Kehm, J and Katz, TA and Boone, DN and Jacobsen, BM and Atkinson, JM and Oesterreich, S and Lee, AV}, title = {Loss of E-cadherin Enhances IGF1-IGF1R Pathway Activation and Sensitizes Breast Cancers to Anti-IGF1R/InsR Inhibitors.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {24}, number = {20}, pages = {5165-5177}, pmid = {29941485}, issn = {1557-3265}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; F31 CA224567/CA/NCI NIH HHS/United States ; R01 CA094118/CA/NCI NIH HHS/United States ; T32 GM008424/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Breast Neoplasms/drug therapy/metabolism/pathology ; Cadherins/genetics/*metabolism ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; *Drug Resistance, Neoplasm ; Drug Synergism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/antagonists & inhibitors/*metabolism ; Mice ; RNA, Small Interfering/genetics ; Receptor, IGF Type 1 ; Receptors, Somatomedin/antagonists & inhibitors/*metabolism ; Signal Transduction/*drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Purpose: Insulin-like growth factor 1 (IGF1) signaling regulates breast cancer initiation and progression and associated cancer phenotypes. We previously identified E-cadherin (CDH1) as a repressor of IGF1 signaling and in this study examined how loss of E-cadherin affects IGF1R signaling and response to anti-IGF1R/insulin receptor (InsR) therapies in breast cancer.Experimental Design: Breast cancer cell lines were used to assess how altered E-cadherin levels regulate IGF1R signaling and response to two anti-IGF1R/InsR therapies. In situ proximity ligation assay (PLA) was used to define interaction between IGF1R and E-cadherin. TCGA RNA-seq and RPPA data were used to compare IGF1R/InsR activation in estrogen receptor-positive (ER+) invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) tumors. ER+ ILC cell lines and xenograft tumor explant cultures were used to evaluate efficacy to IGF1R pathway inhibition in combination with endocrine therapy.Results: Diminished functional E-cadherin increased both activation of IGF1R signaling and efficacy to anti-IGF1R/InsR therapies. PLA demonstrated a direct endogenous interaction between IGF1R and E-cadherin at points of cell-cell contact. Increased expression of IGF1 ligand and levels of IGF1R/InsR phosphorylation were observed in E-cadherin-deficient ER+ ILC compared with IDC tumors. IGF1R pathway inhibitors were effective in inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and similarly IGF1R/InsR inhibition reduced proliferation in ILC tumor explant culture.Conclusions: We provide evidence that loss of E-cadherin hyperactivates the IGF1R pathway and increases sensitivity to IGF1R/InsR targeted therapy, thus identifying the IGF1R pathway as a potential novel target in E-cadherin-deficient breast cancers. Clin Cancer Res; 24(20); 5165-77. ©2018 AACR.}, } @article {pmid29937187, year = {2018}, author = {Chang, HY and Tseng, YK and Chen, YC and Shu, CW and Lin, MI and Liou, HH and Fu, TY and Lin, YC and Ger, LP and Yeh, MH and Liu, PF}, title = {High snail expression predicts a poor prognosis in breast invasive ductal carcinoma patients with HER2/EGFR-positive subtypes.}, journal = {Surgical oncology}, volume = {27}, number = {2}, pages = {314-320}, doi = {10.1016/j.suronc.2018.05.002}, pmid = {29937187}, issn = {1879-3320}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Case-Control Studies ; ErbB Receptors/*metabolism ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Snail Family Transcription Factors/*metabolism ; Survival Rate ; }, abstract = {BACKGROUND: High Snail expression is known as a poor prognostic factor in breast cancer. However, its prognostic impact for breast cancer with different molecular subtypes is still controversial.

METHODS: Snail expression was examined by immunohistochemistry in tissue microarray slides of 85 corresponding tumor-adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues. Multivariable Cox regression analysis was used to assess the impact of Snail expression on survival rate by different molecular subtypes of breast IDC patients.

RESULTS: The level of Snail expression in IDC tumor tissues was significantly higher than that in CTAN tissues. Moreover, high Snail expression had direct impacts on poor disease specific survival (DSS) and disease-free survival (DFS) in breast IDC patients with human epidermal growth factor receptor 2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients with a combination of three prognostic factors, including high Snail expression and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a statistically significant linear trend.

CONCLUSION: High Snail expression could predict a poor prognosis for breast IDC patients with HER2/EGFR-positive subtypes.}, } @article {pmid29936977, year = {2018}, author = {Moten, AS and Lango, MN and Goel, N and Goldberg, AJ}, title = {Regional diagnostic rates, treatments, and outcomes among patients with invasive ductal carcinoma.}, journal = {The Journal of surgical research}, volume = {229}, number = {}, pages = {114-121}, doi = {10.1016/j.jss.2018.03.067}, pmid = {29936977}, issn = {1095-8673}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*diagnosis/epidemiology/therapy ; Carcinoma, Ductal, Breast/*diagnosis/epidemiology/therapy ; Female ; Health Services Accessibility/*statistics & numerical data ; Healthcare Disparities/*statistics & numerical data ; Humans ; Incidence ; Mastectomy/statistics & numerical data ; Middle Aged ; Proportional Hazards Models ; Radiotherapy, Adjuvant/statistics & numerical data ; SEER Program/*statistics & numerical data ; Social Class ; Survival Analysis ; Treatment Outcome ; United States/epidemiology ; }, abstract = {BACKGROUND: The association between regional breast cancer diagnostic rates, treatments, and outcomes is unclear. We sought to investigate the management and survival of women with invasive ductal carcinoma (IDC) from geographic regions with variable rates of diagnosis.

METHODS: Data on women diagnosed with IDC years 2009-2010 were obtained from the Surveillance, Epidemiology, and End Results database. Patients were divided into quartiles based on the IDC diagnostic rate within their county of residence. Chi-square and one-way analysis of variance (ANOVA) analyses tested the association between patient and clinical characteristics and the diagnostic rate quartiles. Cox regression analyses compared survival between the quartiles.

RESULTS: Among the 83,375 patients included, the mean age was 60.8 y and 70.9% were white. Patients residing in counties with the highest diagnostic rates were more frequently white, employed, educated, and wealthier and more often received adjuvant radiation following both partial mastectomy for localized disease and complete mastectomy for advanced disease compared to patients in counties with the lowest diagnostic rates. The highest diagnostic rate quartile had 10% decreased odds of death compared to the lower quartile (hazard ratio: 0.897; 95% confidence interval: 0.832-0.966). However, after adjustment for socioeconomic variables, survival was comparable (hazard ratio: 0.916; 95% confidence interval: 0.835-1.003).

CONCLUSIONS: Regional variation in IDC diagnostic rates is associated with differences in socioeconomic status, grade, stage, and treatment. Patients from regions with the highest rates of diagnosis may have improved access to evidence-based care and resultant superior survival. Enhancing access to care may improve outcomes of patients residing in regions where breast cancer is diagnosed less frequently.}, } @article {pmid29933136, year = {2018}, author = {Nagar, M and Westen, D and Nakash, O}, title = {Reliability of DSM and empirically derived prototype diagnosis for mood, anxiety and personality disorders.}, journal = {Comprehensive psychiatry}, volume = {85}, number = {}, pages = {8-14}, doi = {10.1016/j.comppsych.2018.06.001}, pmid = {29933136}, issn = {1532-8384}, mesh = {Adult ; Anxiety Disorders/*diagnosis ; *Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Male ; Middle Aged ; Mood Disorders/*diagnosis ; Personality Disorders/*diagnosis ; Psychiatric Status Rating Scales/*standards ; Reproducibility of Results ; }, abstract = {BACKGROUND: Prominent psychiatric diagnostic systems such as the DSM-IV and ICD-10 have shown low reliability in clinical practice. An alternative approach to classification of psychiatric disorders is prototype matching. In the current study, we examined reliability of assessing mood, anxiety and personality disorders using a multi-method multi informant approach. More specifically, we examined diagnosis made by treating clinician and independent expert clinical interviewer, using three different diagnostic systems (DSM symptom count, DSM-IV prototype diagnosis and empirically derived prototype diagnosis).

METHODS: A convenience sample of clinicians (N = 80) and patients (N = 170) from eight community mental health clinics in Israel participated in the study.

RESULTS: Our findings show fair to excellent interrater reliability for prototype dimensional diagnostic systems (ranged from 0.40 to 0.79) for most mood and anxiety disorders examined. Overall, dimensional diagnostic systems, yielded better interrater reliability for mood, anxiety and personality disorders, as compared with categorical diagnosis. There were no significant differences between dimensional systems.

CONCLUSIONS: Our findings provide further support to the advantages of dimensional over categorical models in increasing reliability.}, } @article {pmid29932657, year = {2018}, author = {Seo, YH and Jeon, JH and Jeong, M and Ryu, SM and Jeon, WK and Jang, DS and Shim, SH and Lee, D and Choi, JH and Lee, J}, title = {Chemical Constituents of Apios americana Tubers and Their Inhibitory Activities on Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.}, journal = {Journal of natural products}, volume = {81}, number = {7}, pages = {1598-1603}, doi = {10.1021/acs.jnatprod.8b00182}, pmid = {29932657}, issn = {1520-6025}, mesh = {Animals ; Fabaceae/*chemistry ; Lipopolysaccharides ; Macrophages/*drug effects/metabolism ; Mice ; Molecular Structure ; Nitric Oxide/*biosynthesis ; Plant Extracts/*pharmacology ; RAW 264.7 Cells ; }, abstract = {Apios americana is an important food crop producing edible tubers with high nutritional and medicinal values and is widely cultivated in many countries. Despite its usefulness, research on its secondary metabolites and biological activities has been limited. In the present study, a new coumaronochromone, (2 R,3 S)-3,7,4'-trihydroxy-5-methoxycoumaronochromone (1), and two new isoflavone glucosides, 7,2',4'-trihydroxy-5-methoxyisoflavone-4'- O-β-d-glucopyranoside (3) and 5,7,4'-trihydroxyisoflavone-7- O-β-d-gentiotrioside (5), were isolated from the tubers of A. americana via chromatographic separation. Seventeen known compounds (2, 4, and 6-20) were also obtained from this plant part. The chemical structures of 1, 3, and 5 were determined by the interpretation of spectroscopic data. The absolute structure of the new compound 1 was established from experimental and calculated electronic circular dichroism spectra. This is the first study to determine the absolute configuration of a 3-hydroxycoumaronochromone derivative. The potential anti-inflammatory activity of the 20 isolates obtained was evaluated by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Among the isolates, seven compounds (1, 3, 6-8, 15, and 20) showed substantial inhibition of nitric oxide production in RAW 264.7 cells, with the most active being compound 1 (IC50 value of 0.38 ± 0.04 μM).}, } @article {pmid29921380, year = {2018}, author = {Zheng, LJ and Yang, D and Sun, LJ and Li, SS and Wang, JY and Ye, SC}, title = {Different molecular subtypes of breast invasive ductal carcinoma.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {32}, number = {3}, pages = {553-563}, pmid = {29921380}, issn = {0393-974X}, mesh = {*Breast Neoplasms/classification/metabolism/pathology ; *Carcinoma, Ductal, Breast/classification/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*biosynthesis ; Neoplasm Proteins/*biosynthesis ; RNA, Neoplasm/*biosynthesis ; }, abstract = {This study aims to analyze the clinical characteristics of breast invasive ductal carcinoma (BIDC) in patients with different molecular subtypes and identify possible correlation to prognosis. miR- 10b expression level was detected using real-time quantitative polymerase chain reaction (RT-PCR). Tissue sections were collected and stained using the immunohistochemical method. The samples were grouped into human epidermal growth factor receptor 2, (HER2) overexpression, Triple negative, Luminal A and Luminal B groups. Age, tumor size, breast cancer molecular subtype, clinical stage, miR-10b positive expression, positive expression of Ki-67 and survival rate of patients diagnosed with BIDC were analyzed. The expression of miR-10b was down-regulated in the breast carcinoma tissues. Age and clinical stage were distinctly different among patients with different molecular subtypes of BIDC (p less than 0.05). Tumor size was not remarkably different (p less than 0.05) among different subtypes. The positive expression rate of miR-10b was lowest in patients with Luminal B BIDC; the positive expression of Ki-67 was in different correlation with the expression of different receptors, and there was a remarkable difference (p less than 0.05); moreover, the survival rate of patients with Luminal A and B BIDC was significantly higher compared to patients with other molecular subtypes (p less than 0.05). Clinical characteristics and prognosis of BIDC vary among different molecular subtypes. This study provides valuable input on BIDC therapy.}, } @article {pmid29916548, year = {2018}, author = {Lan, VTT and Son, HV and Trang, VL and Trang, NT and Phuong, NT and Toan, NL and Duong, PAT}, title = {Methylation profiles of miR34 gene family in Vietnamese patients suffering from breast and lung cancers.}, journal = {Molecular medicine reports}, volume = {18}, number = {2}, pages = {2476-2484}, doi = {10.3892/mmr.2018.9182}, pmid = {29916548}, issn = {1791-3004}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/pathology ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/epidemiology/*genetics/pathology ; MicroRNAs/*genetics ; Middle Aged ; Promoter Regions, Genetic ; Vietnam/epidemiology ; }, abstract = {The three genes encoding small non‑coding microRNA (miR)34a, MIR34b and MIR34c act as tumor‑suppressor genes. Their aberrant expressions regulated by DNA methylation have been frequently found in various types of cancer. In the present study, the DNA promoter methylation profiles of the MIR34 gene family were analyzed using the methylation specific polymerase chain reaction in order to clarify their association with breast and lung cancer, non‑cancerous or normal adjacent tissues. The methylation frequency of MIR34a was significantly higher in breast cancer (49.37%) compared with normal adjacent tissues (30.38%). The methylation frequency of MIR34b/c was 59.49 and 62.03% in breast cancer and normal adjacent tissues, respectively. MIR34a methylation showed a significant concordance with that of MIR34b/c only in breast cancer tissue. MIR34a methylation was significantly associated with cancer and the invasive ductal carcinoma type of breast cancer (P=0.015 and P=0.02, respectively). Methylation frequency of MIR34a and MIR34b/c was 48.42 and 56.84% in lung cancer, and 47.22 and 51.39% in pulmonary diseases, respectively. No significant association was observed between the methylation status of MIR34a and MIR34b/c, and the clinicopathological features of lung cancer or with those of non‑cancerous pulmonary diseases. Promoter methylation of MIR34a and MIR34b/c occurs frequently and concomitantly in breast and lung cancer, as well as in pulmonary diseases tissues, but not in breast normal tissues adjacent to tumor. These results of the present study emphasize the involvement of MIR34 methylation in human diseases, including cancer. Furthermore, MIR34a methylation may be a promising marker for a subtype of breast cancer.}, } @article {pmid29915849, year = {2018}, author = {Linjawi, S and AlGaithy, Z and Sindi, S and Hamdi, N and Linjawi, A and Alharbi, M}, title = {Regulation of Lipocalin-2 oncogene and its impact on gene polymorphisms on breast cancer patients in Jeddah, Saudi Arabia.}, journal = {Saudi medical journal}, volume = {39}, number = {6}, pages = {558-563}, pmid = {29915849}, issn = {1658-3175}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms/blood/*genetics ; Carcinoma, Ductal, Breast/blood/*genetics ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Lipocalin-2/blood/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Saudi Arabia ; Young Adult ; }, abstract = {OBJECTIVES: To identify the impact of Lipocalin-2 (LCN2) gene polymorphisms on breast cancer patients in western Saudi Arabia.

METHODS: It is a case control study in which blood samples of participants from Medical Reference Clinics and King Abdulaziz University Hospital in Jeddah, Saudi Arabia have been taken between 2014 and 2016. This study recruited 128 participants (50% control, 50% patients) and used Tetra-Primer amplification-refractory mutation system-polymerase chain reaction method for the detection of missense SNP (rs11556770). The study measured LCN2 plasma protein expression by enzyme-linked immunosorbent assay technique. Results: The results have shown that 100% of the genotypes were normal allele (G/G). In contrast, the plasma level of LCN2 was considerably elevated among patients as compared to control (p=0.001), and higher in invasive ductal carcinoma patients (p=0.001). The LCN2 protein expression in plasma level was significantly elevated among patients, particularly who demonstrated invasive ductal carcinoma. Conclusion: There is no significant relationship between breast cancer patients and LCN2 gene polymorphisms   (rs11556770).}, } @article {pmid29915805, year = {2018}, author = {Martin, M and Sabari, JK and Turashvili, G and Halpenny, DF and Rizvi, H and Shapnik, N and Makker, V}, title = {Next-generation sequencing based detection of germline and somatic alterations in a patient with four metachronous primary tumors.}, journal = {Gynecologic oncology reports}, volume = {24}, number = {}, pages = {94-98}, pmid = {29915805}, issn = {2352-5789}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {INTRODUCTION: Multiple primary tumors (MPTs) are defined as two or more separate synchronous or metachronous neoplasms occurring in different sites in the same individual. These tumors differ in histology, as well as primary sites from which they arise. Risk factors associated with the occurrence of MPTs include germline alterations, exposure to prior cancer therapies, occupational hazards, and lifestyle and behavioral influences.

CASE REPORT: We present a case of a patient who was diagnosed with four metachronous primary tumors. In 2013, she was diagnosed with serous proliferations associated with psammomatous bodies of primary peritoneal origin (pT3NxM0). This was followed by invasive ductal carcinoma of the breast (stage pT2N0Mx, histological grade III/III) in 2014, melanoma (stage pT2bNxMx) in 2016 that further advanced to the lung and brain in 2017, and a low-grade lung carcinoid in 2017. To better understand the biology of this patient's MPTs, we performed next-generation sequencing (NGS) to assess for both somatic and germline alterations. The treatment course for this patient aims to target the tumor with the strongest prognostic value, namely her malignant melanoma, and has contributed favorably to the overall survival of this patient.

CONCLUSION: We report the clinical and genomic landscape of a patient with MPTs who had no identifiable unique somatic or germline mutations to explain her predilection to cancer. The treatment course and overall prognosis for this patient is important for understanding future cases with unrelated, metachronous MPTs, the occurrence of which cannot always be explained by underlying genetic mechanisms.}, } @article {pmid29912679, year = {2018}, author = {Khuwuthyakorn, V and Jatuwattana, C and Silvilairat, S and Tantiprapha, W}, title = {Oral indomethacin versus oral ibuprofen for treatment of patent ductus arteriosus: a randomised controlled study in very low-birthweight infants.}, journal = {Paediatrics and international child health}, volume = {38}, number = {3}, pages = {187-192}, doi = {10.1080/20469047.2018.1483566}, pmid = {29912679}, issn = {2046-9055}, mesh = {Administration, Oral ; Cardiovascular Agents/*administration & dosage ; Ductus Arteriosus, Patent/diagnostic imaging/*drug therapy ; Echocardiography ; Female ; Humans ; Ibuprofen/*administration & dosage ; Indomethacin/*administration & dosage ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Male ; Treatment Outcome ; }, abstract = {BACKGROUND: In low- and middle-income countries (LMIC), haemodynamically significant patent ductus arteriosus (hsPDA) is treated with oral indomethacin (IDC) and ibuprofen (IB) instead of intravenous formulations. No significant differences in efficacy have been reported. However, previous studies had small numbers of VLBW infants (<1500 g).

OBJECTIVE: To evaluate the efficacy of oral IDC and IB for closing PDA in VLBW infants with a gestational age of 24-32 weeks.

METHODS: This randomised controlled study enrolled 32 infants with hsPDA for treatment with either three doses of oral IDC or oral IB. Echocardiography was performed before and after treatment.

RESULTS: Oral IDC was more effective than oral IB (65% vs. 27%, p = 0.03). This difference was attributable to the subset of extremely low-birthweight infants (<1000 g) in whom an hsPDA closed 78% of the time after oral IDC compared with 13% of those treated with oral IB (p = 0.01). In contrast, there was no difference in hsPDA closure rates between the study groups of infants with birthweights of 1000-1499 g. There was no significant difference between the drugs in clinical and laboratory measures of adverse effects, nor of other clinical outcomes Conclusion: Oral IDC was more effective than oral IB for closing PDA in VLBW infants, without significant differences in side-effects or short-term outcomes.}, } @article {pmid29906691, year = {2018}, author = {Sakamoto, S and Tsuruga, Y and Fujii, Y and Shomura, H and Hattori, A and Kazui, K}, title = {Intraductal tubulopapillary neoplasm of the pancreas presenting as recurrent acute pancreatitis: A case report.}, journal = {International journal of surgery case reports}, volume = {48}, number = {}, pages = {122-125}, pmid = {29906691}, issn = {2210-2612}, abstract = {INTRODUCTION: The 2010 World Health Organization classification of intraductal neoplasms of the pancreas includes intraductal tubulopapillary neoplasms (ITPNs) and intraductal papillary mucinous neoplasms, the latter being a rare and new concept. ITPN sometimes cause acute pancreatitis; therefore, distinguishing ITPN from idiopathic acute pancreatitis is important but challenging.

PRESENTATION OF CASE: We present the case of a 72-year-old male who had recurrent pancreatitis for the past 2 years, his diagnosis was idiopathic acute pancreatitis. He was admitted to our hospital with severe acute pancreatitis and cholangitis due to intrapancreatic bile duct stenosis. After the treatment of cholangitis, contrast-enhanced computed tomography revealed a tumor at the pancreatic head. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the main pancreatic duct and distal bile duct, and adenocarcinoma was detected using brush cytology of the bile duct stricture and pancreatic juice. The patient was diagnosed with invasive ductal carcinoma and pancreaticoduodenectomy was performed. Histopathological findings revealed dilation of the pancreatic duct, and proliferation of columnar cells and cuboid epithelial cells in the main pancreatic duct of the pancreatic head. Mucus production was poor, and immunostaining results revealed ITPN. The patient is alive and do not exhibit signs of recurrence for 12 months.

DISCUSSION: ITPNs can cause acute pancreatitis, which can be challenging to preoperatively diagnose. ITPNs presenting as acute pancreatitis are rare, with reported only 5 cases.

CONCLUSION: It is important to be keep in mind that there is a possibility of ITPN after diagnosis of idiopathic acute pancreatitis.}, } @article {pmid29905891, year = {2018}, author = {Haslinger, ML and Sosin, M and Bartholomew, AJ and Crocker, A and Gulla, A and Willey, SC and Pittman, TA and Tousimis, EA}, title = {Positive Nipple Margin After Nipple-Sparing Mastectomy: An Alternative and Oncologically Safe Approach to Preserving the Nipple-Areolar Complex.}, journal = {Annals of surgical oncology}, volume = {25}, number = {8}, pages = {2303-2307}, doi = {10.1245/s10434-018-6569-4}, pmid = {29905891}, issn = {1534-4681}, mesh = {Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Disease Management ; Female ; Follow-Up Studies ; Humans ; Margins of Excision ; *Mastectomy, Subcutaneous ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm, Residual/pathology/*surgery ; Nipples/pathology/*surgery ; Retrospective Studies ; Safety ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this study is to describe a less aggressive approach to management of positive nipple margin following nipple-sparing mastectomy (NSM), allowing for preservation of the nipple-areolar complex (NAC).

STUDY DESIGN: A single-institution retrospective chart review was performed for patients undergoing NSM from 1989 to 2017. Positive nipple margin was defined as any residual invasive carcinoma or ductal carcinoma in situ (DCIS) within the additional nipple margin. Management included complete NAC removal, subareolar shave biopsy, or observation alone. Primary outcomes included rates of positive nipple margin and local recurrence.

RESULTS: A total of 819 breasts underwent NSM, yielding a total of 32 breasts (3.9%) with positive nipple margin. Management included 11 (34.4%) subareolar shave biopsies, 15 (46.9%) complete NAC excisions, and 5 (15.6%) with observation alone, plus 1 (3.1%) lost to follow-up. Final pathology after subareolar shave biopsy did not reveal any residual disease, and no patients developed NAC necrosis or required NAC removal. Final pathology after NAC excision revealed 3 of 15 with additional disease (1 invasive ductal carcinoma, 2 DCIS). Of the five patients who had no subsequent intervention, tumor pathology was DCIS in all cases. One patient received adjuvant radiation therapy. Mean time to intervention was 3.7 ± 1.9 with mean follow-up of 2.9 years.

CONCLUSIONS: Management of positive nipple margin after NSM with subareolar shave biopsy is a safe alternative to preserve the NAC.}, } @article {pmid29905049, year = {2018}, author = {Song, D and Li, Z and Zhou, X and Zhang, Y and Peng, X and Zhou, B and Lü, C and Peng, W and Mao, H}, title = {[Application of combined transverse upper gracilis flap and adductor magnus perforator flap in breast reconstruction].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {32}, number = {6}, pages = {707-713}, pmid = {29905049}, issn = {1002-1892}, mesh = {Breast Neoplasms/surgery ; Female ; Humans ; *Mammaplasty/methods ; *Mastectomy ; Neoplasm Recurrence, Local ; *Perforator Flap ; Thigh ; }, abstract = {OBJECTIVE: To explore the clinical application of combined transverse upper gracilis flap and adductor magnus perforator flap in breast reconstruction of breast cancer patients after mastectomy.

METHODS: Between August 2016 and February 2017, the combined transverse upper gracilis flap and adductor magnus perforator flap was used in 12 cases of breast cancer patients who received modified radical surgery for breast reconstruction. All patients were females with the age of 32 to 59 years (mean, 41.5 years). There were 7 cases in left side and 5 cases in right side. Eight cases were received breast reconstruction by one-stage operation and 4 cases by two-stage operation. In one-stage operation cases, pathological diagnosis includes invasive ductal carcinoma in 4 cases and invasive lobular carcinoma in 4 cases. The disease duration ranged from 2 to 9 months (mean, 4.5 months). In two-stage operation cases, the time interval between mastectomy and breast reconstruction ranged from 12 to 70 months (mean, 37.4 months). The length of flap was 20-28 cm, the width of flap was 5.5-7.5 cm, the thickness of flap was 2.5-4.5 cm. The length of gracilis flap pedicle was 6.5-9.2 cm, the length of adductor magnus perforator flap pedicle was 7.5-10.4 cm. The weight of flap was 295-615 g.

RESULTS: The ischemia time of flap ranged from 95 to 230 minutes (mean, 135 minutes). All flaps were successfully survived. All incisions of recipient donor sites healed by first intention. All patients were followed up 7-14 months (mean, 9.5 months). The reconstructed breasts' shape, texture, and elasticity were good and no flap contracture deformation happened. Only linear scar left in the donor sites, but the function of thighs was not affected. No local recurrence happened during follow-up.

CONCLUSION: With appropriate patient selection and surgical technique, the combined transverse upper gracilis flap and adductor magnus perforator flap can be a valuable option as an alternative method for autologous breast reconstruction.}, } @article {pmid29904947, year = {2018}, author = {Dong, C and Liu, Y and Jiang, K and Wang, H and Qu, W and Zhang, C and Liang, R and Gao, Z and Zhao, B and Miao, Q and Shao, S and Wang, L}, title = {The Nogo-B receptor promotes human hepatocellular carcinoma cell growth via the Akt signal pathway.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {9}, pages = {7738-7746}, pmid = {29904947}, issn = {1097-4644}, support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Hepatocellular/genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Knockdown Techniques ; Hep G2 Cells ; Humans ; Liver Neoplasms/genetics/metabolism/*pathology ; Male ; Mice ; Neoplasm Transplantation ; Phosphorylation ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptors, Cell Surface/*genetics/*metabolism ; Signal Transduction ; }, abstract = {Nogo-B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo-B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial-mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES-NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.}, } @article {pmid29900229, year = {2018}, author = {Hong, JH and Ko, YH and Kang, K}, title = {RNA-seq data of invasive ductal carcinoma and adjacent normal tissues from a Korean patient with breast cancer.}, journal = {Data in brief}, volume = {18}, number = {}, pages = {736-739}, pmid = {29900229}, issn = {2352-3409}, abstract = {Invasive ductal carcinoma is the most common type of breast cancer. Here, we provide a whole transcriptome shotgun sequencing (called RNA-seq) dataset conducted with ten samples of invasive ductal carcinoma tissue and three samples of adjacent normal tissue from a single Korean breast cancer patient (luminal B subtype). Differentially expressed genes (DEGs) were identified with a false discovery rate (FDR)-adjusted p-value of 0.05. Gene ontology analysis identified several key pathways, including lymphocyte activation. A list of differentially expressed genes is provided. The raw data was uploaded to the sequence read archive (SRA) database and the BioProject ID is PRJNA432903.}, } @article {pmid29893750, year = {2018}, author = {Arslan, E and Çermik, TF and Trabulus, FDC and Talu, ECK and Başaran, Ş}, title = {Role of 18F-FDG PET/CT in evaluating molecular subtypes and clinicopathological features of primary breast cancer.}, journal = {Nuclear medicine communications}, volume = {39}, number = {7}, pages = {680-690}, doi = {10.1097/MNM.0000000000000856}, pmid = {29893750}, issn = {1473-5628}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: In this study, primary tumors' fluorine-18-fluorodeoxyglucose (F-FDG) uptake in luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 subtypes of breast cancer was evaluated. In addition, the relationship between the primary tumor maximum standardized uptake value (SUVmax) value and the presence of distant metastasis and axillary involvement was evaluated.

PATIENTS AND METHODS: Whole-body F-FDG PET/computed tomography (CT) imaging of 493 patients (mean age; 54.6±13.2 years) diagnosed with primary breast cancer were analyzed retrospectively. PET/CT imaging was obtained 60 min after the intravenous administration of F-FDG. F-FDG uptake of the lesions was assessed by calculating the SUVmax. Histopathological analyses were carried out on the basis of biopsy samples before PET/CT. For histopathological staging, the Scarff Bloom Richardson classification system was utilized, and patients were classified into luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 molecular subtypes.

RESULTS: 82.9% of the patients had invasive ductal carcinoma, 5.8% had invasive lobular carcinoma, 4.2% had apocrine carcinoma, 3.8% had mucinous carcinoma, and 3.4% has mixed carcinoma. Although the highest mean SUVmax was calculated in apocrine tumors (12.4±7.2), the lowest mean SUVmax was calculated in lobular carcinoma (6.8±4.6), and a statistically significant difference was found between the histological groups (P<0.001). F-FDG uptake was reported to be significantly higher in the triple-negative subtype than the luminal types, and in the luminal B subtype than the luminal A subtype. A statistically significant relation was found between primary tumor SUVmax and distant nodal, organ metastasis (P=0.003 and <0.001, respectively).

CONCLUSION: Increased primary tumor F-FDG uptake was associated with aggressive molecular subtypes in this study. The relationship of distant nodal and organ metastasis with primary tumor SUVmax showed that increased F-FDG uptake is important in terms of management of therapy and prognosis.}, } @article {pmid29892197, year = {2018}, author = {Ni, J and Peng, Y and Yang, FL and Xi, X and Huang, XW and He, C}, title = {Overexpression of CLEC3A promotes tumor progression and poor prognosis in breast invasive ductal cancer.}, journal = {OncoTargets and therapy}, volume = {11}, number = {}, pages = {3303-3312}, pmid = {29892197}, issn = {1178-6930}, abstract = {INTRODUCTION: The aim of this study was to evaluate the expression of C-type lectin domain family 3 member A (CLEC3A) and its clinical significance in breast invasive ductal cancer (IDC) as well as its effect on breast cancer (BC) cell proliferation and metastasis. In this study, the level of CLEC3A expression in The Cancer Genome Atlas (TCGA) datasets was analyzed.

MATERIALS AND METHODS: Clinical collected samples and BC cells were measured using quantitative reverse transcription polymerase chain reaction. Its correlations with patients' clinicopathological characteristics were analyzed by Pearson's chi-squared test. Overall survival (OS) analysis was performed by the Kaplan-Meier method and Cox's proportional-hazards model. BC cell proliferation, migration, and invasion by CLEC3A knockdown were assessed using Cell Counting Kit-8 and colony formation assay, wound healing model and transwell assay, respectively, in BT474 cell line. Activities of survival factors and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling were measured by testing key molecules using Western blot assay.

RESULTS: CLEC3A expression was markedly higher in breast IDC tissues than normal breast tissues or adjacent normal tissue. Patients with high CLEC3A expression related to higher lymph node and poorer OS of breast IDC. CLEC3A knockdown by siRNA could inhibit the BC cells BT474 proliferation, migration, and invasion, together with a decrease in expression of key proteins in survival factors and PI3K/AKT signaling pathway.

CONCLUSION: Elevated CLEC3A expression may correlate with breast IDC metastatic potential and indicated a poor prognosis in breast IDC. CLEC3A knockdown inhibited BC cell growth and metastasis might be through suppressing PI3K/AKT signaling activity. These findings unravel that CLEC3A is a promising therapeutic target for BC in the future.}, } @article {pmid29889862, year = {2018}, author = {Awungafac, G and Amin, ET and Fualefac, A and Takah, NF and Agyingi, LA and Nwobegahay, J and Ondoa, P and Njukeng, PA}, title = {Viral load testing and the use of test results for clinical decision making for HIV treatment in Cameroon: An insight into the clinic-laboratory interface.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0198686}, pmid = {29889862}, issn = {1932-6203}, mesh = {Adult ; Aged ; Anti-Retroviral Agents/pharmacology/*therapeutic use ; Cameroon ; Decision Making ; HIV/drug effects ; HIV Infections/*drug therapy/virology ; Humans ; Middle Aged ; Retrospective Studies ; Treatment Failure ; *Viral Load/drug effects ; Young Adult ; }, abstract = {BACKGROUND: The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017.

METHODS: This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers. A simple random pick of six file blocks was performed in each shelf that corresponded to a year of initiation, and the contents of all selected files were reviewed and the information needed for the study entered a structured questionnaire. The data collected was recorded in Epi Info (version 7.1.5.2), and analyzed using SATA (version 12.1; StataCorp LP).

RESULTS: Eight hundred and thirty files were reviewed. The mean duration on ART was 39.4±12 months. Viral load testing uptake was 24.33% and only one VL test had been done by all patients. Approximately 65% of the patients did the first VL after more than 24 months on ART. The median turnaround (TAT) time for VL testing was 6 days (Interquartile range (IQR) 3-7days). Among 201 patients who did a VL test, 94.55% had VL suppression (≤1000copies/mm3). Approximately 54% of the patients with virologic failure were switched to a second-line regimen.

CONCLUSIONS: The uptake of viral load testing is low in North West, South West and West Regions of Cameroon. The current TAT for VL testing is plausible. The rate of switch to second line regimen is low. It is time to strengthen the scale up of VL testing and improve the rate of switch to second-line regimen in Cameroon.}, } @article {pmid29889754, year = {2018}, author = {Kuo, K and Caughey, AB}, title = {Management Strategy for Breast Cancer in Pregnancy.}, journal = {Obstetrics and gynecology}, volume = {132}, number = {1}, pages = {122-125}, doi = {10.1097/AOG.0000000000002647}, pmid = {29889754}, issn = {1873-233X}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/diagnosis/pathology/*therapy ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/pathology/*therapy ; Prenatal Diagnosis ; }, abstract = {A 34-year-old primigravid woman presents for a routine prenatal visit at 18 weeks of gestation with a breast lump. On examination, she has a painless, firm breast mass measuring 3-4 cm in diameter with overlying skin dimpling. A diagnostic mammogram shows findings suspicious for malignancy (Breast Imaging Reporting and Data System [BI-RADS] 4), and core biopsy demonstrates an invasive ductal carcinoma with both estrogen and progesterone receptor-positive staining. The patient asks: "How will this affect my pregnancy, and what is the safest course of action?"}, } @article {pmid29886591, year = {2018}, author = {Liu, JY and Zou, LP and Wu, HJ and Zhao, ZH and Zhang, ZG}, title = {[Effects of ubiquitin-specific proteases 2-69 on proliferation of breast cancer cells].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {47}, number = {6}, pages = {455-460}, doi = {10.3760/cma.j.issn.0529-5807.2018.06.013}, pmid = {29886591}, issn = {0529-5807}, mesh = {Blotting, Western ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; *Cell Proliferation ; Cyclin D1/metabolism ; Endopeptidases/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/genetics/*metabolism ; RNA, Messenger/metabolism ; Transfection ; Tumor Cells, Cultured ; Ubiquitin Thiolesterase ; }, abstract = {Objective: To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast. Methods: Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro. Results: The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells. Conclusions: USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.}, } @article {pmid29884570, year = {2019}, author = {Campo-Sánchez, SM and Camargo-Trillos, J and Calle-Ramírez, JA and Gómez-Wolff, LR and Sánchez-Patiño, LA and García-García, HI}, title = {Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {84}, number = {2}, pages = {174-184}, doi = {10.1016/j.rgmx.2018.04.002}, pmid = {29884570}, issn = {2255-534X}, mesh = {Adenocarcinoma/mortality/therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Colombia/epidemiology ; Colorectal Neoplasms/*mortality/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; *Oncology Service, Hospital ; Retrospective Studies ; Risk Factors ; Sex Factors ; Survival Analysis ; Young Adult ; }, abstract = {INTRODUCTION AND AIMS: In Colombia, cancer of the colon is the third most frequent cancer in relation to incidence and mortality. Five-year survival depends on stage at diagnosis, albeit that rate is not known for the country. The aim of the present study was to characterize the overall survival and disease-free survival rates in an adult population with colorectal cancer treated at an oncology center in Medellín, Colombia.

MATERIALS AND METHODS: A retrospective cohort study was conducted. The case records of patients with a histologic diagnosis of colorectal cancer, seen within the time frame of 2011 and 2015, were reviewed. The overall survival and disease-free survival curves were calculated using the Kaplan-Meier method.

RESULTS: A total of 824 (54.9%) patients with cancer of the colon and 676 (45.1%) with cancer of the rectum were treated. Mean patient age was 63.3 years, female sex predominated (56.3%), and 98.1% of the tumors were adenocarcinomas. The majority of the lesions were stage iii (31.9% in the colon and 35.5% in the rectum) at the time of diagnosis. Surgery was the most frequent treatment in the colon (85.2%) and radiotherapy was the most frequent in the rectum (75.4%). Overall survival at the median follow-up (27.3 months) was 66.7% for cancer of the colon and 63.9% for cancer of the rectum. Disease-free survival at the median follow-up (18.6 months in colon and 14.9 in rectum) was 72.5 and 68.9%, respectively.

CONCLUSIONS: The clinical characteristics and treatment of patients were similar to those found in other studies. Two-year survival was higher than in other Colombian reports and 5-year survival was lower than that observed in developed countries.}, } @article {pmid29881926, year = {2018}, author = {Mapiye, O and Makombe, G and Mapiye, C and Dzama, K}, title = {Limitations and prospects of improving beef cattle production in the smallholder sector: a case of Limpopo Province, South Africa.}, journal = {Tropical animal health and production}, volume = {50}, number = {7}, pages = {1711-1725}, pmid = {29881926}, issn = {1573-7438}, support = {140102//Department of Science and Technology National Research Foundation (DST-NRF) Centre of Excellence (CoE) in Food Security/ ; }, mesh = {Animal Husbandry/*economics/*methods ; Animals ; *Cattle ; Humans ; Logistic Models ; South Africa ; Surveys and Questionnaires ; }, abstract = {The opportunity for the smallholder beef farming system to support the growth of South Africa's livestock industry is untapped. Slow growth of the sector is attributed to many limitations that affect the smallholder beef farming sector. The objectives of the current study were to identify and characterize the systemic challenges and constraints that confront market-oriented smallholder beef farmers in the Limpopo Province, South Africa. Data collection involved interviewing all the 62 farmers under the Limpopo Industrial Development Corporation (IDC)-Nguni project using structured questionnaires. The sample was predominantly males (87%) and adults aged over 45 years (88%). Close to half (47%) of the respondents had tertiary education. Major ecological and production challenges reported as percentages of respondents were drought (96%), rangeland degradation (94%), diseases (89%), feed shortage (86%), and inadequate water (82%). Nearly 50% of the respondents ranked the extent of these challenges as high to very high. Results indicated that poor access to finance, lack of infrastructure, and poor access to markets were some of the key limitations reported by more than 80% of the respondents with above 50% ranking them as high to very high. Logistic regression models showed that respondents' perceptions to the majority of the challenges were largely influenced (p < 0.05) by education, access to formal training, farm size, and age. Given all the limitations found, current findings point to the prospects of designing strategies that support knowledge flows and capacitating the farmers with skills to combat the challenges.}, } @article {pmid29879758, year = {2019}, author = {Choi, CW and Jeong, MH and Park, YS and Son, CH and Lee, HR and Koh, EK}, title = {Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects.}, journal = {Cancer research and treatment}, volume = {51}, number = {2}, pages = {464-473}, pmid = {29879758}, issn = {2005-9256}, support = {50601-2017//Ministry of Science and Technology/ ; 50595-2018//Ministry of Science and Technology/ ; }, mesh = {Animals ; Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology/metabolism ; Cancer Vaccines/*administration & dosage/*immunology ; Cell Line, Tumor ; Combined Modality Therapy ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Disease Models, Animal ; Humans ; Immunotherapy ; Kaplan-Meier Estimate ; Mice ; Neoplasms/*immunology/mortality/pathology/*therapy ; *Radiosurgery/methods ; Tumor Burden ; }, abstract = {PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs).

METHODS AND MATERIALS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system.

RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group.

CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.}, } @article {pmid29879027, year = {2018}, author = {Yin, L and Li, J and Wei, Y and Ma, D and Sun, Y and Sun, Y}, title = {Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review.}, journal = {Medicine}, volume = {97}, number = {23}, pages = {e10900}, pmid = {29879027}, issn = {1536-5964}, mesh = {Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Breast/pathology ; Breast Neoplasms/drug therapy/*pathology ; Endometrial Neoplasms/*pathology ; Endometrium/pathology ; Fatal Outcome ; Female ; Humans ; Laparotomy/methods ; Mastectomy/methods ; Middle Aged ; Ovarian Neoplasms/chemically induced/*pathology ; Ovary/pathology ; Small Cell Lung Carcinoma/chemically induced/*pathology ; Tamoxifen/*adverse effects/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {RATIONALE: Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature.

PATIENT CONCERNS: A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]).

DIAGNOSES: Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient.

INTERVENTIONS: The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor.

OUTCOMES: The patient died of progressive disease 7 months post-operatively.

LESSONS: The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.}, } @article {pmid29878934, year = {2018}, author = {Fine, SW and Al-Ahmadie, HA and Chen, YB and Gopalan, A and Tickoo, SK and Reuter, VE}, title = {Comedonecrosis Revisited: Strong Association With Intraductal Carcinoma of the Prostate.}, journal = {The American journal of surgical pathology}, volume = {42}, number = {8}, pages = {1036-1041}, pmid = {29878934}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Ductal/chemistry/*pathology/surgery ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Necrosis ; Neoplasm Grading ; Predictive Value of Tests ; Prostatic Neoplasms/chemistry/*pathology/surgery ; }, abstract = {From the advent of the Gleason grading system for prostate cancer, cancer displaying intraluminal necrotic cells and/or karyorrhexis within cribriform/solid architecture, a phenomenon termed "comedonecrosis," has been assigned pattern 5. Intraductal carcinoma (IDC-P) shows morphologic overlap with high-grade cribriform/solid adenocarcinoma architecturally and cytologically and may also show central necrosis, yet due to the presence of basal cells at the duct periphery is not currently assigned a grade in clinical practice. On the basis of observations from routine clinical cases, we hypothesized that comedonecrosis was more significantly associated with IDC-P than invasive disease. From a large series of mapped radical prostatectomy specimens (n=933), we identified 125 high-grade (≥Gleason score 4+3=7), high-volume tumors with available slides for review. All slides were examined for the presence of unequivocal comedonecrosis. Standard immunohistochemistry for basal cell markers was performed to detect basal cell labeling in these foci. In total, 19 of 125 (15%) cases showed some ducts with comedonecrosis-9 cases with 1 focus and 10 cases with ≥2 foci; in all, a total of 73 foci of true comedonecrosis were evaluated. Immunohistochemical stains revealed labeling for basal cell markers in a basal cell distribution for at least some comedonecrosis foci in 18 of 19 (95%) cases, 12 with IDC-P exclusively and 6 with a mix of IDC-P and invasive carcinoma comedonecrosis foci. These results suggest that comedonecrosis is strongly associated with IDC-P and hence, the routine assignment of pattern 5 to carcinoma exhibiting comedonecrosis should be reconsidered.}, } @article {pmid29877880, year = {2018}, author = {Manov, JJ and Diaz-Bode, A and Kuker, R}, title = {Hematopoietically Active Adrenal Myelolipoma Mimicking Breast Cancer Metastasis.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {8}, pages = {602-603}, doi = {10.1097/RLU.0000000000002144}, pmid = {29877880}, issn = {1536-0229}, mesh = {Adrenal Gland Neoplasms/*diagnosis/diagnostic imaging/*physiopathology ; Aged ; Breast Neoplasms/*pathology ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; *Hematopoiesis ; Humans ; Myelolipoma/*diagnosis/diagnostic imaging/*physiopathology ; Neoplasm Metastasis ; Positron Emission Tomography Computed Tomography ; }, abstract = {A 66-year old woman had a left breast mass. Biopsy showed invasive ductal carcinoma. A PET/CT scan demonstrated hypermetabolism in the left breast and atypical heterogeneously increased uptake throughout the skeleton as well as a minimally FDG-avid right adrenal myelolipoma. PET/CT 4 months later after 6 cycles of neoadjuvant chemotherapy demonstrated increased size and FDG avidity of this adrenal mass concerning for metastasis and uniformly increased skeletal FDG avidity. Biopsy demonstrated adrenal myelolipoma. The growth and increased FDG avidity of the adrenal myelolipoma were due to the action of colony-stimulating factors on the tumor's hematopoietic component.}, } @article {pmid29877689, year = {2018}, author = {Guo, K and Zhao, L and Yu, S and Zhou, W and Li, Z and Li, G}, title = {A Water-Stable Proton-Conductive Barium(II)-Organic Framework for Ammonia Sensing at High Humidity.}, journal = {Inorganic chemistry}, volume = {57}, number = {12}, pages = {7104-7112}, doi = {10.1021/acs.inorgchem.8b00806}, pmid = {29877689}, issn = {1520-510X}, abstract = {In view of environmental protection and the need for early prediction of major diseases, it is necessary to accurately monitor the change of trace ammonia concentration in air or in exhaled breath. However, the adoption of proton-conductive metal-organic frameworks (MOFs) as smart sensors in this field is limited by a lack of ultrasensitive gas-detecting performance at high relative humidity (RH). Here, the pellet fabrication of a water-stable proton-conductive MOF, Ba(o-CbPhH2IDC)(H2O)4] n (1) (o-CbPhH4IDC = 2-(2-carboxylphenyl)-1 H-imidazole-4,5-dicarboxylic acid) is reported. The MOF 1 displays enhanced sensitivity and selectivity to NH3 gas at high RHs (>85%) and 30 °C, and the sensing mechanism is suggested. The electrochemical impedance gas sensor fabricated by MOF 1 is a promising sensor for ammonia at mild temperature and high RHs.}, } @article {pmid29875947, year = {2018}, author = {Kharmoum, S and Soughi, M}, title = {[Toxidermy mimicking acute chemotherapy-induced lupus erythematosus].}, journal = {The Pan African medical journal}, volume = {29}, number = {}, pages = {66}, doi = {10.11604/pamj.2018.29.66.6083}, pmid = {29875947}, issn = {1937-8688}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Breast Neoplasms/drug therapy ; Capecitabine/administration & dosage ; Carcinoma, Ductal, Breast/drug therapy ; Docetaxel ; Female ; Humans ; Lichenoid Eruptions/*diagnosis/immunology ; Lupus Erythematosus, Cutaneous/chemically induced/*diagnosis ; Middle Aged ; Skin Diseases/*diagnosis/immunology ; Taxoids/administration & dosage ; }, abstract = {Acute chemotherapy-induced lupus erythematosus (ALE) is rare. A few cases have been reported in the literature criminalizing capecitabine, paclitaxel and docetaxel. We report the case of a 64-year old female patient without a history of autoimmune diseases or of drug allergy followed up for invasive ductal carcinoma in the right breast immediately metastatized to the liver and to the lymph nodes. After AC60 first line chemotherapy regimen (a total of 6 cycles), she was treated with docetaxel at a dose of 100 mg/m[2]. After 5 cycles, she had diffuse erythematous lesions on both hands, forearms, cheeks and on the peribuccal area. She underwent corticosteroid therapy with sun protection and could continue the same chemotherapy until the eighth cycle. Patient's evolution was marked by the progression of the disease. She was treated with capecitabine at a dose of 1250 mg/m[2] twice a day. After six cycles she had erythematosquamous and itchy patches on the face resembling the wings of a butterfly (Panel A, Panel B) with oral ulceration and digital pulpitis (Panel C). This initially suggested acute chemotherapy-induced cutaneous lupus erythematosus. Biopsy suggested lichenoid toxidermia. Immunological assessment was performed to exclude chemotherapy-induced cutaneous lupus erythematosus, which showed anti-native DNA antibodies and negative anti-histone antibodies. Anti-nuclear antibody test is positive at 320; this test may be positive in 50-70% of patients with breast cancer, ENT or lymphoma. In the light of these results the diagnosis of toxidermia was the more likely.}, } @article {pmid29874679, year = {2018}, author = {Kopf, S and Groener, JB and Kender, Z and Fleming, T and Brune, M and Riedinger, C and Volk, N and Herpel, E and Pesta, D and Szendrödi, J and Wielpütz, MO and Kauczor, HU and Katus, HA and Kreuter, M and Nawroth, PP}, title = {Breathlessness and Restrictive Lung Disease: An Important Diabetes-Related Feature in Patients with Type 2 Diabetes.}, journal = {Respiration; international review of thoracic diseases}, volume = {96}, number = {1}, pages = {29-40}, doi = {10.1159/000488909}, pmid = {29874679}, issn = {1423-0356}, mesh = {Adult ; Aged ; Diabetes Complications/epidemiology ; Diabetes Mellitus, Type 2/*complications ; Dyspnea/epidemiology/*etiology ; Female ; Humans ; Incidence ; Lung Diseases, Interstitial/diagnosis/*etiology ; Male ; Middle Aged ; Prediabetic State/complications ; Respiratory Function Tests ; Tomography, X-Ray Computed ; Walk Test ; }, abstract = {BACKGROUND: Diabetes mellitus is a significant comorbidity of interstitial lung disease (ILD).

OBJECTIVES: The aim of this study was to investigate the incidence of restrictive lung disease (RLD) and ILD in patients with prediabetes and type 2 diabetes (T2D).

METHODS: Forty-eight nondiabetics, 68 patients with prediabetes, 29 newly diagnosed T2D, and 110 patients with long-term T2D were examined for metabolic control, diabetes-related complications, breathlessness, and lung function. Five participants with T2D, breathlessness, and RLD underwent multidetector computed tomography (MDCT) and a Six-Minute Walk Test (6MWT). Lung tissue from 4 patients without diabetes and from 3 patients with T2D was histologically examined for presence of pulmonary fibrosis.

RESULTS: Breathlessness in combination with RLD was significantly increased in patients with prediabetes and T2D (p < 0.01). RLD was found in 9% of patients with prediabetes, in 20% of patients with newly diagnosed T2D, and in 27% of patients with long-term T2D. Thus, patients with long-term T2D had an increased risk of RLD (OR 5.82 [95% CI 1.71-20.5], p < 0.01). RLD was significantly associated with glucose metabolism and albuminuria (p < 0.01); furthermore, presence of nephropathy increased the risk of RLD (OR 8.57 [95% CI 3.4-21.9], p < 0.01) compared to nondiabetics. MDCT revealed ILD in 4 patients, the 6MWT correlated with the extent of ILD, and histological analysis showed fibrosing ILD in patients with T2D.

CONCLUSIONS: This study demonstrates increased breathlessness and a high prevalence of RLD in patients with T2D, indicating an association between diabetes and fibrosing ILD.}, } @article {pmid29870876, year = {2018}, author = {Mills, MN and Yang, GQ and Oliver, DE and Liveringhouse, CL and Ahmed, KA and Orman, AG and Laronga, C and Hoover, SJ and Khakpour, N and Costa, RLB and Diaz, R}, title = {Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {98}, number = {}, pages = {48-58}, doi = {10.1016/j.ejca.2018.04.011}, pmid = {29870876}, issn = {1879-0852}, mesh = {Adult ; Aged ; Carcinoma, Adenoid Cystic/*pathology/therapy ; Carcinoma, Ductal, Breast/*parasitology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Databases, Factual/statistics & numerical data ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; Triple Negative Breast Neoplasms/*pathology/therapy ; United States ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.

METHODS: A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.

RESULTS: MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC.

CONCLUSION(S): Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments.}, } @article {pmid29869473, year = {2018}, author = {Lahbali, O and Azami, A and Mahdi, Y and El Khannoussi, B}, title = {[Spindle cell carcinoma of the breast : diagnostic difficulties].}, journal = {Revue medicale de Bruxelles}, volume = {39}, number = {3}, pages = {142-145}, doi = {10.30637/2018.16-080}, pmid = {29869473}, issn = {0035-3639}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma/*diagnosis/pathology ; Diagnosis, Differential ; Female ; Humans ; Prognosis ; }, abstract = {The metaplastic breast cancers are rare lesions, accounting for less than 1 % of all breast malignancies. According to the WHO classification (2012), the spindle cell carcinoma of the breast figures among variants of metaplastic carcinomas. The average age at diagnosis is 53 years, and the usual course is fast. Their prognosis is more pejorative than the classic invasive ductal carcinoma. The differential diagnosis arises with sarcomas, especially phyllodes sarcomas but also with other primary breast sarcomas which remain rare. The distinction of this entity is important for further management of patients which is similar to that of conventional infiltrating carcinoma.}, } @article {pmid29867980, year = {2018}, author = {Alamri, A and Rahman, R and Zhang, M and Alamri, A and Gounni, AS and Kung, SKP}, title = {Semaphorin-3E Produced by Immature Dendritic Cells Regulates Activated Natural Killer Cells Migration.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {1005}, pmid = {29867980}, issn = {1664-3224}, mesh = {Animals ; Cell Communication/immunology ; Cells, Cultured ; Cytoskeletal Proteins ; Dendritic Cells/*immunology ; Gene Expression Regulation ; Glycoproteins/*genetics/immunology ; Immunity, Innate ; Killer Cells, Natural/*cytology ; *Lymphocyte Activation ; Membrane Proteins/*genetics/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Semaphorins ; Signal Transduction/immunology ; }, abstract = {Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors. However, possible role(s) of Sema-3E on the regulation of NK-cell functions has not been elucidated. Here, we first demonstrated that DC and NK cells expressed Sema-3E and its receptors, respectively. To formally address the importance of DC-derived Sema-3E in regulating NK-cell migration, we compared in vitro migratory responses of activated NK cells (aNKs) toward different conditioned media of DCs (immature, lipopolysaccharide- or Poly I:C-stimulated) derived from Sema-3E[+/+] or Sema-3E[-/-] mice. We observed that aNKs exhibited enhanced migrations toward the conditioned medium of the immature Sema-3E[-/-] DC, when compared with that of the immature Sema-3E[+/+] DC. Addition of exogenous recombinant Sema-3E to the conditioned medium of the Sema-3E[-/-] immature DC (iDC) abrogated such enhanced NK-cell migration. Our current work revealed a novel role of Sema-3E in limiting NK-cell migrations toward iDC in NK-DC crosstalk.}, } @article {pmid29860265, year = {2018}, author = {Guo, X and Li, J and Zhang, H and Liu, H and Liu, Z and Wei, X}, title = {Relationship Between ADAMTS8, ADAMTS18, and ADAMTS20 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) Expressions and Tumor Molecular Classification, Clinical Pathological Parameters, and Prognosis in Breast Invasive Ductal Carcinoma.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {24}, number = {}, pages = {3726-3735}, pmid = {29860265}, issn = {1643-3750}, mesh = {ADAMTS Proteins/*biosynthesis/genetics ; Adult ; Aged ; Breast Neoplasms/classification/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Transcriptome ; }, abstract = {BACKGROUND The aim of this study was to investigate the correlations between ADAMTSs expression and breast invasive ductal carcinoma (IDC), and to offer a theoretical basis for novel treatment methods for IDC patients. MATERIAL AND METHODS Non-proliferative catheter of breast fibroadenoma (FA) and IDC were used as the normal control and experimental group, respectively. Immunohistochemical (IHC) staining and Western blot (WB) analysis was used to assess protein expression levels of ADAMTS8, ADAMTS18, and ADAMTS20 in both FA and IDC tissues. The results of IHC, the relationship between the protein expression and the tumor molecular classification, and clinical pathological parameters were all evaluated. RESULTS IHC and WB results showed that the expression of ADAMTS8/18 in IDC samples was higher than in FA samples, while the expression of ADAMTS20 in IDC samples was lower than that in FA samples. According to the results of WB, the level of ADAMTS8 was higher in the HER2+ group than in the HER2- group and FA group. The expression of ADAMTS18 in the HR+ (including ER+ and PR+) group was significantly higher than in the HR- group and FA group. The expression of ADAMTS18 protein was also higher in the Ki67+ group than in the Ki67- group. ADAMTS20 was higher in HER2+ IDC compared with the basal subtype of IDC. CONCLUSIONS ADAMTS8/18/20 levels were not significantly correlated to the molecular subtype of IDC. ADAMTS18/20 was significantly associated with histological grade of IDC. ADAMTS8 may predict poor prognosis results of IDC patients.}, } @article {pmid31938422, year = {2018}, author = {Duan, J and Zhen, T and Liang, J and Tang, J and Zhou, Y and Gao, H and Zhang, F and Li, H and Shi, H and Han, A}, title = {The clinicopathological significance of ZNF10 in invasive ductal carcinoma of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {11}, number = {6}, pages = {2968-2979}, pmid = {31938422}, issn = {1936-2625}, abstract = {The aim of this study was to clarify the clinicopathological features and role of zinc finger protein 10 (ZNF10) in breast invasive ductal cancer (IDC). Our data first showed that ZNF10 expression was higher in 8 pairs of fresh breast IDC and breast cancer cell lines compared with their respective adjacent non-tumor breast tissues. ZNF10 expression was significantly higher in IDC compared with DCIS and fibroadenoma of the breast. ZNF10 expression was significantly associated with patients' age, tumor stage, and breast cancer molecular subtype. ZNF10 knockdown inhibited breast cancer cell proliferation, colony formation, cell cycle progression, cell migration, and invasion but induced apoptosis. ZNF10 knockdown also suppressed the tumorigenicity of breast cancer in vivo. The underlying mechanism study showed that ZNF10 regulated the β-catenin signaling pathway in breast cancer. ZNF10 might bind to the region (nucleotides -300 to +100) of the β-catenin promoter. In conclusion, our results first suggest that ZNF10 promotes the carcinogenesis and progression of breast IDC via the β-catenin signaling pathway. Targeting ZNF10 might be a novel treatment strategy for breast cancer.}, } @article {pmid29849809, year = {2018}, author = {Zhao, S and Guo, W and Tan, R and Chen, P and Li, Z and Sun, F and Shao, G}, title = {Correlation between minimum apparent diffusion coefficient values and the histological grade of breast invasive ductal carcinoma.}, journal = {Oncology letters}, volume = {15}, number = {5}, pages = {8134-8140}, pmid = {29849809}, issn = {1792-1074}, abstract = {The present study aimed to investigate the correlation between the minimum apparent diffusion coefficient (ADCmin) value and the histological grade of breast invasive ductal carcinoma (IDC). In total, 129 pathologically verified lesions that were subjected to dynamic breast magnetic resonance imaging and diffusion weighted imaging prior to biopsy were included. The ADCmin value was calculated and its correlation with the tumor histological grade was investigated. Tumors of lower grades demonstrated significantly higher ADCmin values as compared with tumors of higher grades (F=33.49; P<0.01). The mean ADCmin values for IDC of grades I, II and III were (1.14±0.11)×10[-3], (0.99±0.12)×10[-3] and (0.86±0.13)×10[-3] mm[2]/sec, respectively. Statistically significant differences were detected in the mean ADCmin value between tumors of grades II and III (P<0.01), as well as between tumors of grades I and II (P<0.01). In addition, the mean ADCmin values for the less aggressive (grades I and II) and more aggressive (grade III) groups were (1.01±0.13)×10[-3] and (0.86±0.13)×10[-3] mm[2]/sec, respectively (t=5.76, P<0.01). In conclusion, these data indicated that the ADCmin value was correlated with the IDC histological grade, and lower ADCmin values were associated with a higher histological grade and more aggressiveness. Thus, the ADCmin value may be considered as a promising prognostic parameter in identifying tumor aggressiveness.}, } @article {pmid29848684, year = {2018}, author = {Rusak, A and Jablonska, K and Piotrowska, A and Grzegrzolka, J and Nowak, A and Wojnar, A and Dziegiel, P}, title = {The Role of CHI3L1 Expression in Angiogenesis in Invasive Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {38}, number = {6}, pages = {3357-3366}, doi = {10.21873/anticanres.12602}, pmid = {29848684}, issn = {1791-7530}, mesh = {Antigens, CD34/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Chitinase-3-Like Protein 1/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/genetics/*metabolism/pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor C/metabolism ; Vascular Endothelial Growth Factor D/metabolism ; }, abstract = {BACKGROUND/AIM: An increased level of chitinase 3 like 1 protein (CHI3L1) expression is observed in patients with cancer and may have potential prognostic value. The aim of this study was to evaluate the role of CHI3L1 in angiogenesis in invasive ductal breast carcinoma (IDC) (n=110).

MATERIALS AND METHODS: Immunohistochemistry was used to assess the expression of CHI3L1, CD31, CD34, vascular endothelial growth factor (VEGFA, VEGFC and VEGFD). Real-time polymerase chain reaction and western blot were used to determine the level of CHI3L1 mRNA and protein.

RESULTS: Immunohistochemistry demonstrated positive correlation between CHI3L1 expression and angiogenesis markers: CD31 (r=0.34, p=0.0003), CD34 (r=0.24, p=0.012), VEGFD (r=0.24, p=0.013). Higher CHI3L1 expression in estrogen receptor-negative (p=0.041) and progesterone receptor-negative (p=0.014) cancer was observed. Higher CHI3L1 expression was reported in cancer tissues in comparison to non-malignant breast lesions.

CONCLUSION: These results suggest a potential role of CHI3L1 in angiogenesis in IDC and may suggest its involvement in cancer progression.}, } @article {pmid29848352, year = {2018}, author = {Yu, BH and Li, BZ and Zhou, XY and Shi, DR and Yang, WT}, title = {Cytoplasmic FOXP1 expression is correlated with ER and calpain II expression and predicts a poor outcome in breast cancer.}, journal = {Diagnostic pathology}, volume = {13}, number = {1}, pages = {36}, pmid = {29848352}, issn = {1746-1596}, support = {8170019//the youth project of National Nature Science Funding of China/ ; SHDC12014105//Shanghai Hospital Development Center Emerging Advanced Technology Joint Research Project/ ; }, mesh = {Adult ; Biomarkers, Tumor/analysis/metabolism ; Breast Carcinoma In Situ/mortality/pathology ; Breast Neoplasms/mortality/*pathology ; Calpain/analysis/*biosynthesis ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology ; Cytoplasm ; Disease-Free Survival ; Female ; Forkhead Transcription Factors/analysis/*biosynthesis ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Protein Transport/physiology ; Receptors, Estrogen/analysis/*biosynthesis ; Repressor Proteins/analysis/*biosynthesis ; }, abstract = {BACKGROUND: Nuclear forkhead box protein P1 (N-FOXP1) expression in invasive breast cancer has been documented in the literature. However, the FOXP1 expression patterns at different stages of breast cancer progression are largely unknown, and the significance of cytoplasmic FOXP1 (C-FOXP1) expression in breast cancer has not been well illustrated. The aims of this study were to investigate FOXP1 expression patterns in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH) and usual ductal hyperplasia (UDH), and to analyze the clinicopathological relevance of C-FOXP1 and its prognostic value in IDC.

METHODS: N-FOXP1 and C-FOXP1 expression in cases of IDC, DCIS, ADH and UDH was determined using immunohistochemistry. The correlation between C-FOXP1 expression and clinicopathological parameters as well as the overall survival (OS) and disease-free survival (DFS) rates of patients with IDC were analyzed.

RESULTS: Exclusive N-FOXP1 expression was found in 85.0% (17/20), 40.0% (8/20), 12.2% (5/41) and 10.8% (9/83) of UDH, ADH, DCIS, and IDC cases, respectively, and exclusive C-FOXP1 expression was observed in 0% (0/20), 0% (0/20), 4.9% (2/41), and 31.3% (26/83) of the cases, respectively. Both N- and C-FOXP1 staining were observed in 15.0% (3/20), 60.0% (12/20), 82.9% (34/41) and 48.2% (40/83) of the above cases, respectively, while complete loss of FOXP1 expression was observed in only 9.6% (8/83) of IDC cases. Estrogen receptor (ER) expression in C-FOXP1-positive IDC cases (31/66, 47.0%) was significantly lower than that in C-FOXP1-negative cases (13/17, 76.5%) (p = 0.030). Calpain II expression was observed in 83.3% (55/66) of C-FOXP1-positive IDC cases, which was significantly higher than that in C-FOXP1-negative cases (9/17, 52.9%) (p = 0.007). Calpain II was significantly associated with pAKT (p = 0.029), pmTOR (p = 0.011), p4E-BP1 (p < 0.001) and p-p70S6K (p = 0.003) expression levels. The 10-year OS and DFS rates of the C-FOXP1-positive patients were 60.5% and 48.7%, respectively, both of which were lower than those of the C-FOXP1-negative patients (93.3, 75.3%). The OS curve showed a dramatic impact of C-FOXP1 status on OS (p = 0.045).

CONCLUSIONS: Cytoplasmic relocalization of FOXP1 protein was a frequent event in breast IDC. Calpain II might play an important role in nucleocytoplasmic trafficking of FOXP1 and the AKT pathway might be involved in this process. C-FOXP1 expression was inversely associated with ER expression and might be a predictor of poor OS in patients with IDC.}, } @article {pmid29844929, year = {2018}, author = {de Padua, AL and Strickland, K and Patrick, M and Ditunno, JF}, title = {Spinal cord injured women's treatment of breast carcinoma: alert to complications.}, journal = {Spinal cord series and cases}, volume = {4}, number = {}, pages = {46}, pmid = {29844929}, issn = {2058-6124}, abstract = {INTRODUCTION: Women with spinal cord injury (SCI) and who develop breast cancer are a vulnerable and potentially overlooked population. They experience risk factors owing to decreased mobility and are at risk for unique complications from their oncologic treatment.

CASE PRESENTATION: A 54-year-old woman who suffered a T6 AIS A traumatic SCI in 1981, who was diagnosed 32 years later with estrogen receptor and progesterone receptor positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma. During the course of her chemotherapy, she experienced several complications, including reflexive diaphoresis, urinary tract infection, leukopenia, anemia, dehydration, and weakness. These contributed to the development of a stage 4 ischial pressure sore, which required complex treatment.

DISCUSSION: There is a paucity of literature examining the complications of chemotherapy that may be unique to those with SCI. Physiatrists will be seeing more women undergoing oncologic care, as this population of patients ages. A multidisciplinary approach that takes into account the pathophysiologic changes associated with SCI is crucial to understand and prevent complications that could affect their outcomes and contribute to increased cost in a value-based health-care system.}, } @article {pmid29843540, year = {2020}, author = {Kaya, C and Uçak, R and Bozkurt, E and Ömeroğlu, S and Kartal, K and Yazıcı, P and İdiz, UO and Mihmanlı, M}, title = {The Impact of Micropapillary Component Ratio on the Prognosis of Patients With Invasive Micropapillary Breast Carcinoma.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {33}, number = {1}, pages = {31-39}, doi = {10.1080/08941939.2018.1474302}, pmid = {29843540}, issn = {1521-0553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/*pathology/surgery ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/surgery ; Carcinoma, Papillary ; Female ; Humans ; *Mastectomy ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/*epidemiology/pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {Background and Objectives: Invasive micropapillary carcinoma (IMPC) of the breast is a rare and aggressive variant of invasive ductal carcinoma characterized by high-grade lymphovascular invasion and high rates of nodal metastasis. The prognostic significance of the micropapillary component (MC) ratio that constitutes this aggressive variation is controversial. In this study, we aimed to investigate the effect of the MC ratio on the prognosis of these patients. Methods: The data of 47 patients with IMPC were retrospectively reviewed. Patients were divided into two groups: MC ratio of 10-75% (Group 1) and greater than 75% (Group 2). The demographic characteristics of the patients, histopathologic features of the tumors, and survival rates were compared. Results: We detected no significant difference in demographic characteristics between groups 1 and 2 (p = 0.21). No significant difference was detected in terms of tumor diameter, lymph node metastasis, lymphovascular invasion, histologic grade, multicentricity, local recurrence, distant metastasis, and overall survival. Conclusion: In the micropapillary subgroup of invasive ductal carcinoma, although positive receptor characteristics are directly proportional to the increase in MC ratio, recurrence and survival rates are not affected by micropapillary component level.}, } @article {pmid29806309, year = {2018}, author = {Zhou, B and Zhou, X and Li, Z and Peng, X and Yang, L and Lü, C and Song, D and Wu, P and Peng, C}, title = {[Application of indocyanine green-based fluorescent angiography in autologous tissue breast reconstruction].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {32}, number = {4}, pages = {491-494}, pmid = {29806309}, issn = {1002-1892}, mesh = {Adult ; Coloring Agents ; Female ; *Fluorescein Angiography ; Fluorescent Dyes ; Humans ; *Indocyanine Green ; Mammaplasty/*methods ; Mastectomy ; Middle Aged ; Optical Imaging ; Surgical Flaps/*blood supply ; }, abstract = {OBJECTIVE: To investigate the effect of indocyanine green (ICG)-based fluorescent angiography in autologous tissue breast reconstruction.

METHODS: Between June 2016 and June 2017, 14 female patients were treated with the autologous tissue breast reconstruction. The age ranged from 27 to 64 years with the median age of 46.5 years. There were 11 patients of one-stage reconstruction, including 9 with invasive ductal carcinoma of breast, 1 with recurrence tumor on chest wall, and 1 with angiosatcoma in the breast. The disease duration ranged from 9 days to 48 months (mean, 6.8 months). There were 3 patients of second-stage breast reconstruction, who underwent mastectomy 3-4 years ago. During operation, the first ICG-based fluorescent angiography was done before cutting off the flap pedicle. According to the results, 13 patients were adjusted the strategy of operation or cut part of flap, only 1 patient kept the original design. Then, the infusion of flaps were confirmed by the second ICG-based fluorescent angiography after transplanted to the recipient site. The area of flap ranged from 24 cm×11 cm to 36 cm×15 cm. All incisions of recipient site were closed by primary suture.

RESULTS: The fat liquefaction of incision occurred in 1 patient with type 2 diabetes, and the incision healed after debridement operation. The other flaps survived with no flap perfusion related complication. Both donor sites and recipient sites healed by first intention. All patients were followed up 1-14 months (mean, 4 months) with satisfied result of reconstruction. There was no tumor recurrence.

CONCLUSION: ICG-based fluorescent angiography can reveal the perfusion of the flap in operation instantly and accurately. It should be very helpful to adjusting the strategy in reconstructive operation, especially in the large tissue demanded kinds such as breast reconstruction.}, } @article {pmid29805937, year = {2018}, author = {Tyran, M and Cao, M and Raldow, AC and Dang, A and Lamb, J and Low, DA and Steinberg, ML and Lee, P}, title = {Stereotactic Magnetic Resonance-guided Online Adaptive Radiotherapy for Oligometastatic Breast Cancer: A Case Report.}, journal = {Cureus}, volume = {10}, number = {3}, pages = {e2368}, pmid = {29805937}, issn = {2168-8184}, abstract = {We present a case of durable local control achieved in a patient treated with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for an abdominal lymph node in the setting of oligometastatic breast cancer. A 50-year-old woman with a history of triple positive metastatic invasive ductal carcinoma of the left breast, stage IV (T3N2M1), underwent neoadjuvant chemotherapy, mastectomy, adjuvant radiotherapy and maintenance hormonal treatment with HER2 targeted therapies. At 20 months after definitive treatment of her primary, imaging showed an isolated progressive enlargement of lymph nodes between hepatic segment V/IVB and the neck of the pancreas. Radiofrequency ablation was considered, however, this approach was decided not to be optimal due to the proximity to stomach, and pancreatic duct. The patient was treated with SMART for 40 Gray in 5 fractions. Two and a half years later, the patient remains without evidence of disease progression. She experienced Grade 2 acute and late toxicity that was successfully managed with medications. This experience shows that SMART is a feasible and effective treatment to control the abdominal oligometastatic disease for breast cancer.}, } @article {pmid29805754, year = {2018}, author = {Volinia, S and Bertagnolo, V and Grassilli, S and Brugnoli, F and Manfrini, M and Galasso, M and Scatena, C and Mazzanti, CM and Lessi, F and Naccarato, G and Caligo, A and Bianchini, E and Piubello, Q and Orvieto, E and Rugge, M and Natali, C and Reale, D and Vecchione, A and Warner, S and Croce, CM and Capitani, S}, title = {Levels of miR-126 and miR-218 are elevated in ductal carcinoma in situ (DCIS) and inhibit malignant potential of DCIS derived cells.}, journal = {Oncotarget}, volume = {9}, number = {34}, pages = {23543-23553}, pmid = {29805754}, issn = {1949-2553}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; }, abstract = {A substantial number of ductal carcinoma in situ (DCIS) detected by mammography never progress to invasive ductal carcinoma (IDC) and current approaches fail to identify low-risk patients not at need of adjuvant therapies. We aimed to identify the key miRNAs protecting DCIS from malignant evolution, that may constitute markers for non-invasive lesions. We studied 100 archived DCIS samples, including pure DCIS, DCIS with adjacent IDC and pure DCIS from patients with subsequent IDC in contralateral breast or no recurrence. A DCIS derived cell line was used for molecular and cellular studies. A genome wide study revealed that pure DCIS has higher miR-126 and miR-218 expression than DCIS with adjacent IDC lesions or than IDC. The down-regulation of miR-126 and miR-218 promoted invasiveness in vitro and, in patients with pure DCIS, was associated with later onset of IDC. Survival studies of independent cohorts indicated that both miRNAs play a protective role in IDC. The clinical findings are in agreement with the miRNAs' roles in cell adhesion, differentiation and proliferation. We propose that miR-126 and miR-218 have a protective role in DCIS and represent novel biomarkers for the risk assessment in women with early detection of breast cancer.}, } @article {pmid29805680, year = {2018}, author = {Yoshikawa, M and Iinuma, H and Umemoto, Y and Yanagisawa, T and Matsumoto, A and Jinno, H}, title = {Exosome-encapsulated microRNA-223-3p as a minimally invasive biomarker for the early detection of invasive breast cancer.}, journal = {Oncology letters}, volume = {15}, number = {6}, pages = {9584-9592}, pmid = {29805680}, issn = {1792-1074}, abstract = {Patients diagnosed preoperatively with ductal carcinoma in situ (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome-encapsulated microRNA-223-3p (miR-223-3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR-223-3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR-223-3p levels of IDC patients demonstrated the highest fold-change compared with those in the DCIS patients and healthy controls. The potential of miR-223-3p for cell proliferation and cell invasion were examined in vitro using MCF7 cells transfected with the miR-223-3p gene. MCF7 cells transfected with the miR-223-3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR-223-3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR-223-3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR-223-3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR-223-3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR-223-3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome-encapsulated miR-223-3p level was significantly associated with the malignancy of breast cancer.}, } @article {pmid29805554, year = {2018}, author = {Chen, S and Qiu, Y and Guo, P and Pu, T and Feng, Y and Bu, H}, title = {FGFR1 and HER1 or HER2 co-amplification in breast cancer indicate poor prognosis.}, journal = {Oncology letters}, volume = {15}, number = {6}, pages = {8206-8214}, pmid = {29805554}, issn = {1792-1074}, abstract = {Human epidermal growth factor receptor 1 or 2 (HER1/2), and fibroblast growth factor receptor 1 (FGFR1) signaling serve critical roles in the progression of breast cancer; however, cross-talk between HER1/2 and FGFR1 signaling has not been extensively studied. In the present study, the copy number variation status of FGFR1 and HER1/2, and the clinical implications and prognostic relevance of this, were evaluated in invasive ductal breast cancer (IDC) tissue samples. Quantitative polymerase chain reaction and fluorescence in situ hybridization were used to assess gene copy number variation in IDC samples, and the clinical characteristics and survival curves of patients with IDC were analyzed. The amplification of FGFR1 was identified in 16.0% of the samples (12 of 75), of HER1 in 26.7% (20 of 75), of HER2 in 37.3% (28 of 75), and of FGFR1 and HER1/2 simultaneously in 8.0% (6 of 75). FGFR1 and HER1/2 co-amplification were significantly correlated with distant metastasis (P=0.035), recurrence (P=0.026) and decreased disease-free survival time (P=0.042). This was the case for patients undergoing endocrine therapy (P=0.002) and chemotherapy (P=0.044). Taken together, the results indicate that patients with FGFR1 and HER1/2 co-amplification may exhibit a less favorable prognosis compared with patients with either FGFR1, HER1/2 amplification or without amplification.}, } @article {pmid29804148, year = {2018}, author = {Santangelo, G and Bisecco, A and Trojano, L and Sacco, R and Siciliano, M and d'Ambrosio, A and Della Corte, M and Lavorgna, L and Bonavita, S and Tedeschi, G and Gallo, A}, title = {Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.}, journal = {Journal of neurology}, volume = {265}, number = {8}, pages = {1772-1779}, pmid = {29804148}, issn = {1432-1459}, mesh = {Adolescent ; Adult ; Atrophy ; Brain/*diagnostic imaging ; Cognition Disorders/diagnostic imaging/etiology ; *Cognitive Reserve ; Cross-Sectional Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/complications/*diagnostic imaging/*psychology ; Organ Size ; Young Adult ; }, abstract = {Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.}, } @article {pmid29804074, year = {2018}, author = {Schellenberg, AE and Wood, ML and Baniak, N and Hayes, P}, title = {Metastatic ductal carcinoma of the breast to colonic mucosa.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29804074}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*secondary ; Colonic Neoplasms/diagnosis/*secondary ; Colonoscopy ; Female ; Humans ; Incidental Findings ; Intestinal Mucosa/pathology ; Rectal Neoplasms/diagnosis/*secondary ; }, abstract = {Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.}, } @article {pmid29802656, year = {2018}, author = {Neville, G and Neill, CO and Murphy, R and Corrigan, M and Redmond, PH and Feeley, L and Bennett, MW and O'Connell, F and Browne, TJ}, title = {Is excision biopsy of fibroadenomas based solely on size criteria warranted?.}, journal = {The breast journal}, volume = {24}, number = {6}, pages = {981-985}, doi = {10.1111/tbj.13069}, pmid = {29802656}, issn = {1524-4741}, mesh = {Adult ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/*pathology/surgery ; Female ; Fibroadenoma/*pathology/surgery ; Humans ; Image-Guided Biopsy ; Middle Aged ; }, abstract = {Fibroadenomas (FA) are the most common benign tumor in the female breast. Most are managed conservatively provided there is clinical, radiologic, and pathologic concordance. However, surgical excision is typically recommended for cellular fibroepithelial lesions or those lesions with clinical, radiologic, or pathologic features concerning for phyllodes tumor (PT). Some studies have suggested surgical excision in all FA >30 mm to reduce core needle biopsy (CNB) sampling errors. The aim of our study was to evaluate, in the absence of any other concerning clinicopathologic features, whether surgical excision of FA was warranted based on size criteria alone. Cork University Hospital is a large academic center in Southern Ireland. Its breast cancer center provides both a screening and symptomatic service and diagnoses approximately 600 cancers per year. The breast histopathological data base was reviewed for all CNBs from January 1, 2010, to June 30, 2015, with a diagnosis of FA that went on to have excision at our institution. We excluded all cellular fibroepithelial lesions and those cases with co-existent lobular neoplasia, ductal carcinoma in situ, invasive carcinoma, atypical ductal hyperplasia, or lesions which would require excision in their own right. Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. Patient demographics and preoperative radiologic size and the radiologic target were recorded in each case. All radiology was reviewed by a breast radiologist prior to inclusion in the study, and there was histologic radiologic concordance with a diagnosis of FA in all cases. A total of 12,109 consecutive radiologically guided CNB were performed January 2010-June 2015; 3438 with a diagnosis of FA were identified of which 290 cases went on to have surgical excision. Of those 290 cases; 98.28% (n = 285) were confirmed as FA on excision. The remaining 1.72% (n = 5) had atypical features-FA with LCIS (n = 1), benign PT (n = 3), and invasive ductal carcinoma (n = 1). Our study suggests that, excision based solely on size is not warranted in clinical and radiologically concordant cases with a diagnosis of FA on CNB.}, } @article {pmid29802469, year = {2018}, author = {Di Oto, E and Biserni, GB and Varga, Z and Morandi, L and Cucchi, MC and Masetti, R and Foschini, MP}, title = {X chromosome gain is related to increased androgen receptor expression in male breast cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {473}, number = {2}, pages = {155-163}, pmid = {29802469}, issn = {1432-2307}, support = {Fundamentally Oriented Funds for Research - RFO//Università di Bologna/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Chromosomes, Human, X/genetics ; Gene Amplification ; Genes, X-Linked/*genetics ; Humans ; Male ; Middle Aged ; Receptors, Androgen/biosynthesis/*genetics ; *Sex Chromosome Aberrations ; }, abstract = {X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.}, } @article {pmid29798568, year = {2017}, author = {Chai, L and Zhang, X}, title = {[Application of serratus anterior muscle flap combined with breast implants for breast reconstruction after modified radical mastectomy].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {31}, number = {9}, pages = {1098-1101}, pmid = {29798568}, issn = {1002-1892}, mesh = {Adult ; Breast Implants ; Breast Neoplasms/*surgery ; Female ; Humans ; *Mammaplasty ; Mastectomy ; *Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Recurrence, Local ; Surgical Flaps ; Young Adult ; }, abstract = {OBJECTIVE: To investigate effectiveness of the combination of serratus anterior muscle flap and breast implants for breast reconstruction after modified radical mastectomy.

METHODS: Between January 2015 and December 2015, 25 female patients with breast cancer were enrolled, aged 24-62 years (mean, 40.6 years). The tumor located at left side in 9 cases and right side in 16 cases; 14 cases were in the left upper quadrant, 4 cases were in the left lower quadrant, 7 cases were on the top of the breast. All cases were invasive ductal carcinoma. According to TNM staging, 14 cases were at stageⅠand 11 cases were at stageⅡA. The diameter of lumps were all less than 3 cm. All those lumps were solitary and without distant metastasis. The sentinel nodes were all negative. After modified radical mastectomy, the breasts were reconstructed by serratus anterior muscle flap and breast implants. The nipples were spared in 22 cases.

RESULTS: The operation time was 113-148 minutes (mean, 136 minutes). All breasts survived and incisions healed at stageⅠ. There was no complication such as hematoma, infection, etc. All patients were followed up 6-18 months (mean, 15 months). Except 1 case, the others were evaluated according to the criteria of the reconstructed breast at 12 months after operation. Among them, 23 cases were evaluated as good and 1 case as fair. There was no tumor recurrence during the follow-up period.

CONCLUSION: The combination of serratus anterior muscle flap and breast implants after the modified radical mastectomy is a handy approach of breast reconstruction which is less harmful with few postoperative complications. It also gains a high degree of satisfaction from patients for good breast shape.}, } @article {pmid29792742, year = {2018}, author = {Cohen, EO and Tso, HH and Phalak, KA and Mayo, RC and Leung, JWT}, title = {Screening Mammography Findings From One Standard Projection Only in the Era of Full-Field Digital Mammography and Digital Breast Tomosynthesis.}, journal = {AJR. American journal of roentgenology}, volume = {211}, number = {2}, pages = {445-451}, doi = {10.2214/AJR.17.19023}, pmid = {29792742}, issn = {1546-3141}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Early Detection of Cancer/methods ; Female ; Humans ; Mammography/*methods ; Mass Screening ; Middle Aged ; Predictive Value of Tests ; Radiographic Image Enhancement/*methods ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Retrospective Studies ; }, abstract = {OBJECTIVE: The purpose of this article is to compare outcomes of findings seen on one view only from screening full-field digital mammography (FFDM) and FFDM plus digital breast tomosynthesis (DBT).

MATERIALS AND METHODS: A retrospective review was performed of 103,070 consecutive screening mammograms obtained from February 2011 through June 2014 at two community-based breast centers. Recalled findings prospectively seen on one view only were analyzed. Pearson chi-square test and Fisher exact test were performed, and 95% CIs were determined.

RESULTS: Mammograms were acquired using FFDM (n = 71,656) and FFDM-DBT (n = 31,414) during the study period, and 2213 FFDM (3.1%) and 433 FFDM-DBT (1.4%) mammograms were recalled for one-view-only findings (p < 0.0001). The final study population (1592 FFDM and 354 FFDM-DBT) was defined after 689 of these recalled FFDM and 92 of these recalled FFDM-DBT examinations were excluded for insufficient mammographic follow-up (< 24 months). Summation artifacts accounted for more one-view-only findings from FFDM (1067/1592; 67.0%) than FFDM-DBT (190/354; 53.7%) (p < 0.0001). In the FFDM cohort, 28 one-view-only findings proved malignant (24 invasive ductal carcinoma [IDC], one invasive lobular carcinoma [ILC], and three ductal carcinoma in situ [DCIS]). In the FFDM-DBT cohort, 14 one-view-only findings proved malignant (11 IDC, one ILC, and two DCIS). The positive predictive value (PPV) of a one-view-only finding was significantly lower for FFDM (1.8%) than for FFDM-DBT (4.0%) (p = 0.010).

CONCLUSION: One-view-only findings occur with both FFDM and FFDM-DBT and remain an important but uncommon sign of malignancy. They are more frequent, are more likely to represent summation artifacts, and have a lower PPV with FFDM than with FFDM-DBT.}, } @article {pmid29790210, year = {2018}, author = {Sun, Z and Yu, S and Zhao, L and Wang, J and Li, Z and Li, G}, title = {A Highly Stable Two-Dimensional Copper(II) Organic Framework for Proton Conduction and Ammonia Impedance Sensing.}, journal = {Chemistry (Weinheim an der Bergstrasse, Germany)}, volume = {24}, number = {42}, pages = {10829-10839}, doi = {10.1002/chem.201801844}, pmid = {29790210}, issn = {1521-3765}, abstract = {This work reports the design and fabrication of a proton conductive 2D metal-organic framework (MOF), [Cu(p-IPhHIDC)]n (1) (p-IPhH3 IDC=2-(p-N-imidazol-1-yl)-phenyl-1 H-imidazole-4,5-dicarboxylic acid) as an advanced ammonia impedance sensor at room temperature and 68-98 % relative humidity (RH). MOF 1 shows the optimized proton conductivity value of 1.51×10[-3] S cm[-1] at 100 °C and 98 % RH. Its temperature-dependent and humidity-dependent proton conduction properties have been explored. The large amount of uncoordinated carboxylate groups between the layers plays a vital role in the resultant conductivity. Distinctly, the fabricated MOF-based sensor displays the required stability toward NH3 , enhanced sensitivity, and notable selectivity for NH3 gas. At room temperature and 68 % RH, it gives a remarkable gas response of 8620 % to 130 ppm NH3 gas and lower detection limit of 2 ppm towards NH3 gas. It is also found that the gas response of the ammonia sensor increases linearly with the increase of NH3 gas concentration under 68-98 % RH and room temperature. Moreover, the sensor indicates excellent reversibility and selectivity toward NH3 versus N2 , H2 , O2 , CO, CO2 , benzene, and MeOH. Based on structural analyses, activation energy calculations, water and NH3 vapor absorptions, and PXRD determinations, proton conduction and NH3 sensing mechanisms are suggested.}, } @article {pmid29789520, year = {2018}, author = {Hu, CC and Chang, TH and Hsu, HH and Pen, YJ and Yu, JC}, title = {T1-Weighted Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Distinguish Between Concurrent Cholesterol Granuloma and Invasive Ductal Carcinoma of the Breast: A Case Report.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {593-598}, pmid = {29789520}, issn = {1941-5923}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; *Cholesterol ; Contrast Media ; Diagnosis, Differential ; Elasticity Imaging Techniques ; Female ; Granuloma, Foreign-Body/*diagnostic imaging ; Humans ; *Magnetic Resonance Imaging ; *Mammography ; Middle Aged ; }, abstract = {BACKGROUND Cholesterol granuloma is a benign condition that can be misdiagnosed as breast cancer on mammographic and ultrasound imaging. A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast was imaged with ultrasound elastography and magnetic resonance imaging (MRI) methods, including T1-weighted dynamic contrast-enhanced MRI (DCE-MRI), before biopsy and histopathology. CASE REPORT A 52-year-old woman, with a previous history of intraduct papillomas in both breasts, underwent six-monthly follow-up breast imaging. The most recent breast mammogram showed a progressively enlarging oval mass in the upper inner quadrant (UIQ) of the left breast, and an adjacent irregular mass with microcalcifications. Virtual Touch IQ (VTIQ) shear wave elastography was used with ultrasound of the breast lesions. T1-weighted fat saturation (T1WFS) MRI, T2-weighted short-tau inversion recovery (STIR) MRI, and T1-weighted DCE-MRI were used to image the left breast. T1-weighted DCE-MRI showed that the oval lesion had a high T1-weighted signal and mild progressive enhancement, with a Type I (benign) time-signal intensity curve; the second, irregular, mass showed rapid, intense enhancement with a washout pattern or Type III (malignant) time-signal intensity curve. Histopathology confirmed that the oval mass was a cholesterol granuloma, and the irregular mass was an invasive ductal carcinoma. CONCLUSIONS A case of concomitant cholesterol granuloma with invasive ductal carcinoma of the left breast, showed that ultrasound with shear wave elastography and T1-weighted DCE-MRI could distinguish between cholesterol granuloma and invasive ductal carcinoma.}, } @article {pmid29789230, year = {2018}, author = {Chang Sen, LQ and Mayo, RC and Lesslie, MD and Yang, WT and Leung, JWT}, title = {Impact of Second-Opinion Interpretation of Breast Imaging Studies in Patients Not Currently Diagnosed With Breast Cancer.}, journal = {Journal of the American College of Radiology : JACR}, volume = {15}, number = {7}, pages = {980-987.e1}, doi = {10.1016/j.jacr.2018.03.055}, pmid = {29789230}, issn = {1558-349X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Mammography ; Middle Aged ; Predictive Value of Tests ; *Referral and Consultation ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: To study the impact of second-opinion interpretation of breast imaging studies submitted from outside facilities to a tertiary cancer center.

MATERIALS AND METHODS: A retrospective database review was conducted of second-opinion interpretations rendered at our institution from January 1, 2010, to June 30, 2014, on studies from patients who did not have a concurrent breast cancer diagnosis. A total of 2,253 patients were included.

RESULTS: In 800 of 2,253 patients (35.5%), the BI-RADS categories assigned at our institution and at outside facilities were discordant. Of 973 patients assigned BI-RADS category 4 or 5 at outside facilities, 278 (28.6%) were assigned BI-RADS category 1 to 3 (no biopsy necessary) at our institution. Of 923 patients assigned BI-RADS category 1 to 3 at outside facilities, 191 (20.7%) were assigned BI-RADS category 4 or 5 at our institution, and 189 of these had biopsies, which revealed 23 cancers, 15 high-risk lesions, and 151 benign lesions. One high-risk lesion at core biopsy was upgraded to invasive ductal carcinoma and ductal carcinoma in situ (DCIS) on excision, resulting in 24 cancers. Of these, 18 reflected true additional breast cancers detected as a result of second-opinion interpretation: 12 invasive carcinomas and 6 cases of DCIS. These results translate into a 9.4% (18/191) positive predictive value for the number of cancers diagnosed among all biopsies recommended and a 9.5% (18/189) positive predictive value for the number of cancers diagnosed among all biopsies recommended and actually performed.

CONCLUSIONS: These findings demonstrate the positive clinical impact of second-opinion interpretation at a tertiary cancer center of outside-facility breast imaging studies in patients without a breast cancer diagnosis.}, } @article {pmid29786772, year = {2018}, author = {Watanabe, Y and Anan, K and Saimura, M and Koga, K and Fujino, M and Mine, M and Tamiya, S and Nishihara, K and Nakano, T and Mitsuyama, S}, title = {Upstaging to invasive ductal carcinoma after mastectomy for ductal carcinoma in situ: predictive factors and role of sentinel lymph node biopsy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {25}, number = {6}, pages = {663-670}, doi = {10.1007/s12282-018-0871-7}, pmid = {29786772}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mastectomy ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS.

METHODS: The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed.

RESULTS: Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0-3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis.

CONCLUSIONS: Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0-3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB.}, } @article {pmid29783647, year = {2018}, author = {Rucco, R and Sorriso, A and Liparoti, M and Ferraioli, G and Sorrentino, P and Ambrosanio, M and Baselice, F}, title = {Type and Location of Wearable Sensors for Monitoring Falls during Static and Dynamic Tasks in Healthy Elderly: A Review.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {5}, pages = {}, pmid = {29783647}, issn = {1424-8220}, mesh = {Accidental Falls/*prevention & control ; Aged ; Biosensing Techniques/*methods ; Humans ; Monitoring, Ambulatory ; *Monitoring, Physiologic ; *Wearable Electronic Devices ; }, abstract = {In recent years, the meaning of successful living has moved from extending lifetime to improving the quality of aging, mainly in terms of high cognitive and physical functioning together with avoiding diseases. In healthy elderly, falls represent an alarming accident both in terms of number of events and the consequent decrease in the quality of life. Stability control is a key approach for studying the genesis of falls, for detecting the event and trying to develop methodologies to prevent it. Wearable sensors have proved to be very useful in monitoring and analyzing the stability of subjects. Within this manuscript, a review of the approaches proposed in the literature for fall risk assessment, fall prevention and fall detection in healthy elderly is provided. The review has been carried out by using the most adopted publication databases and by defining a search strategy based on keywords and boolean algebra constructs. The analysis aims at evaluating the state of the art of such kind of monitoring, both in terms of most adopted sensor technologies and of their location on the human body. The review has been extended to both dynamic and static analyses. In order to provide a useful tool for researchers involved in this field, the manuscript also focuses on the tests conducted in the analyzed studies, mainly in terms of characteristics of the population involved and of the tasks used. Finally, the main trends related to sensor typology, sensor location and tasks have been identified.}, } @article {pmid29782423, year = {2018}, author = {Adler, G and Shahar, B and Dolev, T and Zilcha-Mano, S}, title = {The Development of the Working Alliance and Its Ability to Predict Outcome in Emotion-Focused Therapy for Social Anxiety Disorder.}, journal = {The Journal of nervous and mental disease}, volume = {206}, number = {6}, pages = {446-454}, doi = {10.1097/NMD.0000000000000814}, pmid = {29782423}, issn = {1539-736X}, mesh = {Adolescent ; Adult ; Aged ; *Emotion-Focused Therapy ; Female ; Humans ; Interview, Psychological ; Male ; Middle Aged ; Phobia, Social/psychology/*therapy ; Psychiatric Status Rating Scales ; Surveys and Questionnaires ; *Therapeutic Alliance ; Treatment Outcome ; Young Adult ; }, abstract = {The study focuses on the alliance of 12 patients receiving emotion-focused therapy for social anxiety. Anxiety symptoms and patient perception of the working alliance were examined weekly. The first eight sessions of each patient were coded for within- and between-sessions alliance levels (1008 segments were coded). At the sample level, the alliance shows linear development over time but high variability between individuals. More than half the patients showed alliance development consistent with the rupture-resolution pattern. Without accounting for the temporal relationship between alliance and symptoms, alliance significantly predicted symptoms across treatment. When we accounted for the temporal relationship between alliance and symptoms, we found that symptoms can predict alliance but alliance cannot predict symptoms. We obtained the same findings using patient-rated and coded alliance.}, } @article {pmid29774321, year = {2018}, author = {Güven, HE and Kültüroğlu, MO and Gülçelik, MA and Özaslan, C}, title = {Sentinel Lymph Node Metastasis in Invasive Lobular Carcinoma of the Breast.}, journal = {European journal of breast health}, volume = {14}, number = {2}, pages = {117-120}, pmid = {29774321}, issn = {2587-0831}, abstract = {OBJECTIVE: Invasive lobular carcinoma (ILC) of the breast makes up 5 to 15 percent of all invasive breast cancers. It has distinctive clinical and histopathological features when compared to invasive ductal carcinoma (IDC). This study intends to describe factors influencing sentinel lymph node (SLN) positivity in patients with "pure" ILC.

MATERIALS AND METHODS: Data of 105 patients, who were treated at a tertiary oncology center, with lobular carcinoma of the breast that were subjected to SLN biopsy was probed retrospectively. Patients were categorized as ≤60 and >60 years of age, positive or negative for estrogen receptor and progesterone, tumor grade I, II and III, Ki67≤15% and >30%, lymphovascular invasion presence and the presence of multicentricity and multifocality.

RESULTS: Mean age at the time of diagnosis was 52 (38-81). Mean tumor size was 2.7 cm (0.7-13cm). Univariate analyses revealed a significant relationship between tumor size (≤2 cm vs >2cm) and metastasis in the SLN. This relation kept its significance in multivariate analyses. (p=0.013).

CONCLUSION: With so many different characteristics from IDC, ILC is mostly a uniform tumor. In this study, tumor size was the only independent clinical parameter that was found related to SLN metastases.}, } @article {pmid29772102, year = {2018}, author = {Zhao, J and Sun, G and Liao, B and Zhang, X and Armstrong, CM and Yin, X and Liu, J and Chen, J and Yang, Y and Zhao, P and Tang, Q and Wang, Z and Chen, Z and Li, X and Wei, Q and Li, X and Chen, N and Gao, AC and Shen, P and Zeng, H}, title = {Novel nomograms for castration-resistant prostate cancer and survival outcome in patients with de novo bone metastatic prostate cancer.}, journal = {BJU international}, volume = {122}, number = {6}, pages = {994-1002}, doi = {10.1111/bju.14398}, pmid = {29772102}, issn = {1464-410X}, mesh = {Aged ; Bone Neoplasms/drug therapy/metabolism/*secondary ; Humans ; Male ; Models, Statistical ; *Nomograms ; Prostate-Specific Antigen/analysis ; Prostatic Neoplasms, Castration-Resistant/metabolism/mortality/*pathology ; Survival Analysis ; }, abstract = {OBJECTIVES: To develop nomograms predicting the incidence of castration-resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa).

PATIENTS AND METHODS: Data from 449 patients with de novo metastatic PCa were retrospectively analysed. Patients were randomly divided into a training (n = 314, 70%) and a validation cohort (n = 135, 30%). Predictive factors were selected using a Cox proportional hazards model and were further used for building predictive models. The outcomes were incidence of CRPC and OS.

RESULTS: Predictive factors included: Gleason score (GS), intraductal carcinoma of the prostate (IDC-P), Eastern Cooperative Oncology Group status, and alkaline phosphatase, haemoglobin and prostate-specific antigen levels. IDC-P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated concordance index of 0.762 and 0.723, respectively. Based on the β coefficients of the final model, risk classification systems were constructed. For those with favourable, intermediate and poor prognosis, the median time to CRPC was 62.6, 28.0 and 13.0 months (P < 0.001), respectively; and the median OS was not reached, 55.0 and 33.0 months, respectively (P < 0.001).

CONCLUSIONS: We developed two novel nomograms to predict the incidence of CRPC and OS for patients with de novo metastatic PCa. These tools may assist in physician decision-making and the designing of clinical trials.}, } @article {pmid29770285, year = {2018}, author = {Peters, J and Tsai, WC and Peters, G}, title = {Large Non-enhancing Breast Cancer on Breast Magnetic Resonance Imaging: A Case Report.}, journal = {Cureus}, volume = {10}, number = {3}, pages = {e2332}, pmid = {29770285}, issn = {2168-8184}, abstract = {A 55-year-old female presented with vague symptoms in the lateral left breast. Digital breast tomosynthesis and breast ultrasound showed no focal lesion, and magnetic resonance imaging (MRI) was subsequently performed. No suspicious enhancement was seen on MRI; in particular, no suspicious lesion was seen in the area of clinical concern. In view of persisting focal mastalgia and vague parenchymal changes in the symptomatic area on repeat targeted ultrasound, a core biopsy was performed. Final pathology after left mastectomy with axillary clearance showed a 42 mm grade 2 invasive ductal carcinoma. Ten out of 15 lymph nodes contained metastatic carcinoma. This case report presents a large ductal breast cancer with no enhancement on breast MRI. Factors that may contribute to the non-detection of breast cancers on MRI studies will be discussed.}, } @article {pmid29760696, year = {2018}, author = {Cougoule, C and Lastrucci, C and Guiet, R and Mascarau, R and Meunier, E and Lugo-Villarino, G and Neyrolles, O and Poincloux, R and Maridonneau-Parini, I}, title = {Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {846}, pmid = {29760696}, issn = {1664-3224}, mesh = {Cell Differentiation ; *Cell Movement ; Cells, Cultured ; Chemokines/immunology ; Dendrites/immunology ; Dendritic Cells/*cytology/enzymology ; Endopeptidases/*metabolism ; Humans ; Macrophages/immunology ; Podosomes/*immunology ; Toll-Like Receptors/immunology ; rho-Associated Kinases/immunology ; }, abstract = {Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo, or in collagen matrices in vitro. However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam3CSK4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE2, known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to migrate in 3D dense environments, which relies on their capacity to form podosomes independent of their maturation status, paving the way of further investigations on in vivo DC migration in dense tissues and its regulation during infections.}, } @article {pmid29759595, year = {2018}, author = {Da Ros, L and Moretti, A and Querzoli, P and Pedriali, M and Lupini, L and Bassi, C and Carcoforo, P and Negrini, M and Frassoldati, A}, title = {HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights.}, journal = {Clinical breast cancer}, volume = {18}, number = {5}, pages = {e1133-e1139}, doi = {10.1016/j.clbc.2018.04.006}, pmid = {29759595}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/therapeutic use ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Carcinoma, Lobular/drug therapy/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local/epidemiology ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab/therapeutic use ; }, abstract = {BACKGROUND: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC).

PATIENTS AND METHODS: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients.

RESULTS: Two hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P < .0001) and node-positive (54.1% vs. 45%, P = .013) disease of lower proliferative activity (Mib1 < 20%: 51.4% vs. 22.3%, P < .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P = .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations.

CONCLUSION: HER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.}, } @article {pmid29755815, year = {2018}, author = {Çoşğun, İG and Kaçan, T and Erten, G}, title = {Late Endobronchial Pulmonary Metastasis in a Patient with Breast Cancer.}, journal = {Turkish thoracic journal}, volume = {19}, number = {2}, pages = {97-99}, pmid = {29755815}, issn = {2149-2530}, abstract = {The lung is a common location for malignant metastases. However, endobronchial metastases from nonpulmonary neoplasms are rare. Metastatic breast cancer usually occurs in 2-3 years of the disease course. A 65-year-old woman visited our hospital for the evaluation of dry cough. The patient had a history of breast cancer, which was treated with modified radical mastectomy and axillary dissection 10 years ago; she was then treated with aromatase inhibitor for 5 years. Chest X-ray revealed right hilum enlargement. Thorax computed tomography revealed a 35-mm diameter mass that was localized in the right hilum. Fiberoptic bronchoscopy was performed, and an endobronchial lesion was observed in the right main lobe carina. Pathological evaluation revealed that the mass was a metastasis of the invasive ductal carcinoma of the breast. Weekly paklitaxel chemotherapy was initiated because of the symptomatic disease. We reported the case of a patient with breast cancer who had an endobronchial metastasis. Her disease-free interval was 10 years. This case indicates that a long-term follow-up of breast cancer is necessary, and biopsies must be performed to make a final diagnosis when any suspicious hilum enlargement is observed.}, } @article {pmid29755651, year = {2018}, author = {Laes, JF and Aftimos, P and Barthelemy, P and Bellmunt, J and Berchem, G and Camps, C and Peñas, RL and Finzel, A and García-Foncillas, J and Hervonen, P and Wahid, I and Joensuu, T and Kathan, L and Kong, A and Mackay, J and Mikropoulos, C and Mokbel, K and Mouysset, JL and Odarchenko, S and Perren, TJ and Pienaar, R and Regonesi, C and Alkhayyat, SS and El Kinge, AR and Abulkhair, O and Galal, KM and Ghanem, H and El Karak, F and Garcia, A and Ghitti, G and Sadik, H}, title = {The clinical impact of using complex molecular profiling strategies in routine oncology practice.}, journal = {Oncotarget}, volume = {9}, number = {29}, pages = {20282-20293}, pmid = {29755651}, issn = {1949-2553}, abstract = {Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.}, } @article {pmid29755382, year = {2018}, author = {Mioni, G and Stablum, F and Grondin, S and Altoé, G and Zakay, D}, title = {Effect of the Symbolic Meaning of Speed on the Perceived Duration of Children and Adults.}, journal = {Frontiers in psychology}, volume = {9}, number = {}, pages = {521}, pmid = {29755382}, issn = {1664-1078}, abstract = {The present study investigated how the symbolic meaning of speed affects time perception in children and adults. We employed a time reproduction task in which participants were asked to reproduce temporal intervals previously presented. In Experiment 1, 45 primary school children and 22 university students performed a time reproduction task with cars (meaning of fastness) and trucks (meaning of slowness) presented for 11 and 21 s in static and moving conditions. Results showed that young children under-reproduced the duration more than the older children and adults, especially when the stimulus presented was a car. Moreover, participants under-reproduced moving stimuli compared to static one. In Experiment 2, we tested 289 participants who were divided into nine different age groups according to their school class: five from primary school, three from Junior High, and one from the university. Participants performed a time reproduction task with a motorbike (meaning of fastness) or a bicycle (meaning of slowness) under static and moving conditions for 11, 21, and 36 s. The results confirmed the effects of symbolic meaning of speed on children's time perception and showed that vehicles that evoked the idea of fastness were under-reproduced compared to stimuli evoking the idea of slowness.}, } @article {pmid29751292, year = {2018}, author = {Maida, A and Zota, A and Vegiopoulos, A and Appak-Baskoy, S and Augustin, HG and Heikenwalder, M and Herzig, S and Rose, AJ}, title = {Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance.}, journal = {The Journal of nutritional biochemistry}, volume = {57}, number = {}, pages = {189-196}, doi = {10.1016/j.jnutbio.2018.03.027}, pmid = {29751292}, issn = {1873-4847}, support = {//CIHR/Canada ; }, mesh = {Animals ; CD36 Antigens/genetics ; Dietary Proteins/*pharmacology ; Dyslipidemias/*diet therapy/etiology/metabolism ; Fatty Acids/*metabolism ; Fibroblast Growth Factors/*metabolism ; Hypertriglyceridemia/diet therapy/etiology ; Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Non-alcoholic Fatty Liver Disease/diet therapy/etiology ; Obesity/*complications/metabolism ; }, abstract = {Recent studies have demonstrated that dietary protein dilution (PD) can promote metabolic inefficiency and improve glucose metabolism. However, whether PD can promote other aspects of metabolic health, such as improve systemic lipid metabolism, and mechanisms therein remains unknown. Mouse models of obesity, such as high-fat-diet-fed C57Bl/6 N mice, and New Zealand Obese mice were fed normal (i.e., 20%P) and protein-dilute (i.e., 5%EP) diets. FGF21-/- and Cd36-/- and corresponding littermate +/+ controls were also studied to examine gene-diet interactions. Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21). Furthermore, PD greatly enhances systemic lipid homeostasis, the mechanisms by which include FGF21-stimulated, and cluster of differentiation 36 (CD36) mediated, fatty acid clearance by oxidative tissues, such as heart and brown adipose tissue. Taken together, our preclinical studies demonstrate a novel nutritional strategy, as well as highlight a role for FGF21-stimulated systemic lipid metabolism, in combating obesity-related dyslipidemia.}, } @article {pmid29748534, year = {2018}, author = {Ladislau, L and Portilho, DM and Courau, T and Solares-Pérez, A and Negroni, E and Lainé, J and Klatzmann, D and Bonomo, A and Allenbach, Y and Benveniste, O and Riederer, I and Savino, W and Mouly, V and Butler-Browne, G and Benjamim, CF}, title = {Activated dendritic cells modulate proliferation and differentiation of human myoblasts.}, journal = {Cell death & disease}, volume = {9}, number = {5}, pages = {551}, pmid = {29748534}, issn = {2041-4889}, mesh = {Adult ; Antigens, Differentiation/biosynthesis ; *Cell Differentiation ; *Cell Proliferation ; Dendritic Cells/cytology/*metabolism ; Female ; Humans ; Infant, Newborn ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Myoblasts, Skeletal/cytology/*metabolism ; }, abstract = {Idiopathic Inflammatory Myopathies (IIMs) are a heterogeneous group of autoimmune diseases affecting skeletal muscle tissue homeostasis. They are characterized by muscle weakness and inflammatory infiltration with tissue damage. Amongst the cells in the muscle inflammatory infiltration, dendritic cells (DCs) are potent antigen-presenting and key components in autoimmunity exhibiting an increased activation in inflamed tissues. Since, the IIMs are characterized by the focal necrosis/regeneration and muscle atrophy, we hypothesized that DCs may play a role in these processes. Due to the absence of a reliable in vivo model for IIMs, we first performed co-culture experiments with immature DCs (iDC) or LPS-activated DCs (actDC) and proliferating myoblasts or differentiating myotubes. We demonstrated that both iDC or actDCs tightly interact with myoblasts and myotubes, increased myoblast proliferation and migration, but inhibited myotube differentiation. We also observed that actDCs increased HLA-ABC, HLA-DR, VLA-5, and VLA-6 expression and induced cytokine secretion on myoblasts. In an in vivo regeneration model, the co-injection of human myoblasts and DCs enhanced human myoblast migration, whereas the absolute number of human myofibres was unchanged. In conclusion, we suggest that in the early stages of myositis, DCs may play a crucial role in inducing muscle-damage through cell-cell contact and inflammatory cytokine secretion, leading to muscle regeneration impairment.}, } @article {pmid29748110, year = {2018}, author = {Santangelo, G and Vitale, C and Baiano, C and D'Iorio, A and Longo, K and Barone, P and Amboni, M and Conson, M}, title = {Interoceptive processing deficit: A behavioral marker for subtyping Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {53}, number = {}, pages = {64-69}, doi = {10.1016/j.parkreldis.2018.05.001}, pmid = {29748110}, issn = {1873-5126}, mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Interoception/*physiology ; Male ; Middle Aged ; Parkinson Disease/*classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; }, abstract = {BACKGROUND: Non-motor symptoms in Parkinson's disease (PD), such as cognitive, emotional, autonomic and somatosensory alterations, are not ubiquitous but vary between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes of the syndrome. Non-motor phenomena (e.g., anxiety, depression and apathy) have been related to representation of autonomic and somatosensory sensations (interoception), and recent findings suggest interoceptive deficits in PD.

OBJECTIVES: To test whether interoceptive processing is differently affected in TD and PIGD phenotypes, by assessing both interoceptive accuracy and sensibility in PD patients with TD and PIGD subtypes, and in healthy controls.

METHODS: Interoceptive accuracy was measured by the heartbeat perception task requiring participants to count their own heartbeats in a given time interval. A time-estimation, control task was also administered asking participants to count the seconds in a set period of time. Interoceptive sensibility was assessed by a questionnaire of subjective interoception. Finally, the patients underwent measures of anxiety, depression, apathy and anhedonia, and impulsive-compulsive disturbances.

RESULTS: The main results showed reduced interoceptive accuracy and sensibility in TD patients relative to both PIGD patients and healthy controls. Reduced interoceptive accuracy of TD group was a reliable result since their performance on the time estimation control task was comparable to that of both PIGD patients and healthy controls.

CONCLUSIONS: These findings demonstrate that the behavioural assessment of different aspects of interoceptive processing can provide with a further marker for subtyping patients with PD.}, } @article {pmid29745077, year = {2018}, author = {Marusa Borgonio-Cuadra, V and Miranda-Duarte, A and Rojas-Toledo, X and Garcia-Hernandez, N and Alfredo Sierra-Ramirez, J and Cardenas-Garcia, M and Elena Hernandez-Caballero, M}, title = {Association between promoter hypermethylation of the DACT2 gene and tumor stages in breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {23}, number = {2}, pages = {361-365}, pmid = {29745077}, issn = {1107-0625}, mesh = {Adaptor Proteins, Signal Transducing ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Line, Tumor ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genetic Association Studies ; Humans ; Middle Aged ; Neoplasm Proteins/*genetics ; Neoplasm Staging ; Promoter Regions, Genetic ; }, abstract = {PURPOSE: Aberrant methylation of CpG islands in the promoter is a hallmark of cancer, leading to transcriptional silencing of tumor suppressor genes. The aim of this work was to evaluate the promoter methylation status of the DACT2 gene in breast cancer (BC) tissue and to analyze its possible effect on tumor type or grade.

METHODS: CpG island from the DACT2 promoter in region -240 to -14 from transcriptional start site (TSS) were obtained. Through the use of sodium bisulfite DNA conversion analysis, followed by detection with MSP (methylation specific PCR), we analyzed 79 BC and 15 adjacent healthy samples.

RESULTS: T he c ases a nalyzed w ere i n s tage I (2.5%), I I (38%), or III (59.5%). The most frequent tumor type was invasive ductal carcinoma (71.4%). Methylation analysis comparing tumor tissues with adjacent non-cancerous tissues showed statistical significance. Methylation was observed in 32.9% (26/79) of the samples; no methylation was found in adjacent healthy tissue. DACT2 methylation was associated with tumor stage I-II (p=0.03) and stage III (p=0.004).

CONCLUSION: An association was found of DACT2 promoter methylation with advanced tumor stages. This gene has been suggested as a potential biomarker, however, more investigation is required to validate this function.}, } @article {pmid29739984, year = {2018}, author = {Du, T and Zhu, L and Levine, KM and Tasdemir, N and Lee, AV and Vignali, DAA and Houten, BV and Tseng, GC and Oesterreich, S}, title = {Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7205}, pmid = {29739984}, issn = {2045-2322}, support = {F30 CA203154/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Atlases as Topic ; Breast Neoplasms/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Ductal, Breast/diagnosis/genetics/*immunology/metabolism ; Carcinoma, Lobular/diagnosis/genetics/*immunology/metabolism ; Cell Line, Tumor ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human ; Humans ; Immune System/immunology/metabolism/pathology ; Immunotherapy/methods ; Lymphatic Metastasis ; Metabolic Networks and Pathways/genetics/*immunology ; Middle Aged ; Neoplasm Proteins/classification/genetics/*immunology/metabolism ; Neoplasm Recurrence, Local/diagnosis/genetics/*immunology/metabolism ; Protein Biosynthesis ; Tumor Escape/genetics ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.}, } @article {pmid29737006, year = {2018}, author = {Reut, N and Kanat-Maymon, Y}, title = {Spouses' prenatal autonomous motivation to have a child and postpartum depression symptoms.}, journal = {Journal of clinical psychology}, volume = {74}, number = {10}, pages = {1808-1819}, doi = {10.1002/jclp.22630}, pmid = {29737006}, issn = {1097-4679}, mesh = {Adult ; Depression/*psychology ; Depression, Postpartum/*psychology ; Fathers/*psychology ; Female ; Humans ; Longitudinal Studies ; Male ; Mothers/*psychology ; *Motivation ; *Personal Autonomy ; Pregnancy ; Spouses/*psychology ; Young Adult ; }, abstract = {OBJECTIVES: Maternal postpartum depression symptoms (PDS) are linked with negative personal, family, and child developmental outcomes. However, paternal PDS, let alone dyadic process, are understudied. Grounded in the Self-Determination Theory of motivation, this longitudinal study examined whether mothers' and fathers' type of prenatal motivation to have a child predicted depression symptoms 3-6 months after birth.

METHOD: The data (N = 90 heterosexual couples) were analyzed using the Actor-Partner Interdependence Model.

RESULTS: Dyadic analyses showed that a person's prenatal autonomous motivation to have a child significantly predicted own PDS and partner's PDS. Importantly, these finding were equivalent across genders.

CONCLUSIONS: The findings highlight the importance of dyadic prenatal motivational processes as antecedents of PDS.}, } @article {pmid29736850, year = {2018}, author = {van der Velden, BHM and Sutton, EJ and Carbonaro, LA and Pijnappel, RM and Morris, EA and Gilhuijs, KGA}, title = {Contralateral parenchymal enhancement on dynamic contrast-enhanced MRI reproduces as a biomarker of survival in ER-positive/HER2-negative breast cancer patients.}, journal = {European radiology}, volume = {28}, number = {11}, pages = {4705-4716}, pmid = {29736850}, issn = {1432-1084}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; 12725//Stichting voor de Technische Wetenschappen/ ; }, mesh = {Adult ; Aged ; Biomarkers ; Breast Neoplasms/*diagnostic imaging/therapy ; Contrast Media/*administration & dosage ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Recurrence, Local ; Parenchymal Tissue/*diagnostic imaging ; Propensity Score ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; }, abstract = {OBJECTIVES: To assess whether contralateral parenchymal enhancement reproduces as an independent biomarker for patient survival in an independent patient cohort from a different cancer institution.

METHODS: This is a HIPAA-compliant IRB approved retrospective study. Patients with ER-positive/HER2-negative operable invasive ductal carcinoma and preoperative dynamic contrast-enhanced MRI were consecutively included between 2005 and 2009. The parenchyma of the breast contralateral to known cancer was segmented automatically on MRI and contralateral parenchymal enhancement (CPE) was calculated. CPE was split into tertiles and tested for association with invasive disease-free survival (IDFS) and overall survival (OS). Propensity score analysis with inverse probability weighting (IPW) was used to adjust CPE for patient and tumour characteristics as well as systemic therapy.

RESULTS: Three hundred and two patients were included. The median age at diagnosis was 48 years (interquartile range, 42-57). Median follow-up was 88 months (interquartile range, 76-102); 15/302 (5%) patients died and 37/302 (13%) had a recurrence or died. In context of multivariable analysis, IPW-adjusted CPE was associated with IDFS [hazard ratio (HR) = 0.27, 95% confidence interval (CI) = 0.05-0.68, p = 0.004] and OS (HR = 0.22, 95% CI = 0.00-0.83, p = 0.032).

CONCLUSIONS: Contralateral parenchymal enhancement on pre-treatment dynamic contrast-enhanced MRI as an independent biomarker of survival in patients with ER-positive/HER2-negative breast cancer has been upheld in this study. These findings are a promising next step towards a practical and inexpensive test for risk stratification of ER-positive/HER2-negative breast cancer.

KEY POINTS: • High parenchymal-enhancement in the disease-free contralateral breast reproduces as biomarker for survival. • This is in patients with ER-positive/HER2-negative breast cancer from an independent cancer centre. • This is independent of patient and pathology parameters and systemic therapy.}, } @article {pmid29734605, year = {2018}, author = {Marull, J and Tello, E and Bagaria, G and Font, X and Cattaneo, C and Pino, J}, title = {Exploring the links between social metabolism and biodiversity distribution across landscape gradients: A regional-scale contribution to the land-sharing versus land-sparing debate.}, journal = {The Science of the total environment}, volume = {619-620}, number = {}, pages = {1272-1285}, doi = {10.1016/j.scitotenv.2017.11.196}, pmid = {29734605}, issn = {1879-1026}, mesh = {Animals ; *Biodiversity ; Conservation of Natural Resources/methods ; Environmental Monitoring/*methods ; }, abstract = {The debate about the relative merits of the 'land-sparing' and 'land-sharing' approaches to biodiversity conservation is usually addressed at local scale. Here, however, we undertake a regional-scale approach to this issue by exploring the association between the Human Appropriation of Net Primary Production (HANPP) and biodiversity components (plants, amphibians, reptiles, birds and mammals) across a gradient of human-transformed landscapes in Catalonia, Spain. We propose an Intermediate Disturbance Complexity (IDC) model to assess how human disturbance of the photosynthetic capacity affects the landscape patterns and processes that host biodiversity. This model enables us to explore the association between social metabolism (HANPP), landscape structure (composition and spatial configuration) and biodiversity (species richness) by using Negative Binomial Regression (NBR), Exploratory Factor Analysis (EFA) and Structural Equation Modelling (SEM). The empirical association between IDC and landscape complexity and HANPP in Catalonia confirms the expected values of the intermediate disturbance hypothesis. There is some increase in biodiversity when high IDC values correspond to landscape mosaics. NBR and EFA show positive associations between species richness and increasing values of IDC and forest cover for all biodiversity groups except birds. SEM shows that total biodiversity is positively determined by forest cover and, to a lesser extent, by HANPP, and that both factors are negatively associated with each other. The results suggest that 'natural' landscapes (i.e. those dominated by forests) and agroforestry mosaics (i.e. heterogeneous landscapes characterized by a set of land uses possessing contrasting disturbances) provide a synergetic contribution to biodiversity conservation. This 'virtuous triangle' consisting of forest cover, HANPP and biodiversity illustrates the complex human-nature relationships that exist across landscape gradients of human transformation. This energy-landscape integrated analysis provides a robust assessment of the ecological impact of land-use policies at regional scale.}, } @article {pmid29733543, year = {2018}, author = {Nahleh, Z and Otoukesh, S and Mirshahidi, HR and Nguyen, AL and Nagaraj, G and Botrus, G and Badri, N and Diab, N and Alvarado, A and Sanchez, LA and Dwivedi, AK}, title = {Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics.}, journal = {Cancer medicine}, volume = {7}, number = {6}, pages = {2710-2717}, pmid = {29733543}, issn = {2045-7634}, mesh = {Black or African American ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/metabolism/pathology/therapy ; Disease Management ; Ethnicity ; Female ; *Healthcare Disparities ; *Hispanic or Latino ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; }, abstract = {UNLABELLED: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico- pathological characteristics and disparities in breast cancer in this group at two tertiary care University-based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ & HER2- as opposed to 71% in non-Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American).

CONCLUSION: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR) = 2.05, P < 0.001), triple negative tumors (RRR = 2.64, P < 0.0001), HER2 + /HR - disease (RRR = 1.77, P < 0.0001), and less HR+ /HER2- BC (RRR = 0.69, P < 0.0001). Hispanics and African Americans are diagnosed with breast cancer at a younger age, have a higher prevalence of Triple negative breast cancer, and are diagnosed at more advanced stages of disease. Increasing awareness and targeting minority populations for health promotion interventions, screening and early detection continue to be of paramount importance to reduce the burden of health disparities.}, } @article {pmid29730038, year = {2018}, author = {Abraham, E and Feldman, R}, title = {The neurobiology of human allomaternal care; implications for fathering, coparenting, and children's social development.}, journal = {Physiology & behavior}, volume = {193}, number = {Pt A}, pages = {25-34}, doi = {10.1016/j.physbeh.2017.12.034}, pmid = {29730038}, issn = {1873-507X}, mesh = {Animals ; Brain/*physiology ; Child ; Child Development/*physiology ; Female ; Humans ; Male ; Maternal Behavior/physiology/psychology ; Neurosecretory Systems/metabolism ; *Parenting ; Paternal Behavior/*physiology/psychology ; *Social Behavior ; }, abstract = {Allomothering, the caregiving to offspring by adults other than the biological mother including fathers and other group members, has characterized human societies throughout hominin evolution. Allomothering is common across the animal kingdom and carries long-term fitness benefits to offspring. Guided by our biobehavioral synchrony conceptual frame, we present research from our lab and others addressing the behavioral, hormonal, and neural systems that underpin human allomaternal care by fathers and studies on the coparental bond. Several important aspects of human allomothering are discussed: (i) father-child synchrony, (ii) longitudinal effects of fathering and coparenting on child outcomes (iii) cultural variability in paternal care, (iv) the role of oxytocin, vasopressin, prolactin, and testosterone in the formation and maintenance of human fathering, (v) evolutionary changes in fathers' brains within the parent-offspring interface and their contribution to children's long-term social adaptation, and (vi) the neural correlates of human coparenting. Based on our findings we propose that in the course of hominin evolution fathers' neuroendocrine systems, brain functionality and integrity, and behavioral responses to infant cues have undergone profound natural selection to accommodate the great variability in the paternal role across time and place, culminating in the contemporary cooperative, highly involved coparent observed in modern societies of the developed world.}, } @article {pmid29725408, year = {2018}, author = {Zhou, SJ and Bi, TQ and Qin, CX and Yang, XQ and Pang, K}, title = {Expression of NAMPT is associated with breast invasive ductal carcinoma development and prognosis.}, journal = {Oncology letters}, volume = {15}, number = {5}, pages = {6648-6654}, pmid = {29725408}, issn = {1792-1074}, abstract = {Nicotinamide phosphoribosyltransferase (NAMPT) possesses various functions in human cells, and altered NAMPT expression is associated with human carcinogenesis. The present study detected the expression of NAMPT in normal and cancerous breast tissues from 83 patients using immunohistochemistry, and analyzed its association with the clinicopathological and survival data of the patients. NAMPT was significantly overexpressed in the breast invasive ductal carcinoma tissues compared with adjacent normal mammary gland tissues. Upregulated NAMPT expression was associated with a larger tumor size, lymph node metastasis, advanced clinical tumor-node-metastasis stages, and estrogen receptor and progesterone receptor expression. Furthermore, NAMPT expression was associated with poor overall and disease-free survival in patients with breast cancer. In conclusion, NAMPT increased protein expression in tumor cells may contribute to the development and progression of breast invasive ductal carcinoma. Thus, detection of NAMPT expression might be useful as a biomarker for the early detection and prognosis prediction of breast cancer.}, } @article {pmid29722170, year = {2018}, author = {Zhao, Y and Sun, HF and Chen, MT and Gao, SP and Li, LD and Jiang, HL and Jin, W}, title = {Clinicopathological characteristics and survival outcomes in Paget disease: a SEER population-based study.}, journal = {Cancer medicine}, volume = {7}, number = {6}, pages = {2307-2318}, pmid = {29722170}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*diagnosis/mortality/pathology ; Prognosis ; SEER Program ; Survival Analysis ; Young Adult ; }, abstract = {The objective of this study was to investigate the clinicopathological characteristics and survival outcomes of Paget disease (PD), Paget disease concomitant infiltrating duct carcinoma (PD-IDC), and Paget disease concomitant intraductal carcinoma (PD-DCIS). We identified 501,631 female patients from 2000 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database. These identified patients included patients with PD (n = 469), patients with PD-IDC (n = 1832), and patients with PD-DCIS (n = 1130) and infiltrating ductal carcinoma (IDC) (n = 498,076). Then, we compared the clinical characteristics of these patients with those who were diagnosed with IDC during the same period. The outcomes of these subtypes of breast carcinoma were different. Based on the overall survival, the patients with PD-IDC had the worst prognosis (5-year survival rate = 84.1%). The PD-DCIS had the best prognosis (5-year survival rate = 97.5%). Besides, among patients with Paget disease, the one who was married had a better prognosis than who were not. And, according to our research, the marital status was associated with the hormone receptor status in patients with PD-IDC. Among three subtypes of Paget disease, patients with PD-IDC had the worst prognosis. Besides, patients who were unmarried had worse outcomes. And the marital status of patients with PD-IDC is associated with hormone status. The observation underscores the importance of individualized treatment.}, } @article {pmid31938381, year = {2018}, author = {Pu, T and Zhong, X and Deng, L and Li, S and Qiu, Y and Liu, Y and Zheng, H and Ye, F and Bu, H}, title = {Long term prognosis of ductal carcinoma in situ with microinvasion: a retrospective cohort study.}, journal = {International journal of clinical and experimental pathology}, volume = {11}, number = {5}, pages = {2665-2674}, pmid = {31938381}, issn = {1936-2625}, abstract = {Ductal carcinoma in situ with microinvasion (DCIS-Mi) is an early-stage breast cancer with long-term behavior, prognosis and treatment not fully understood. The aim of our study was to explore the clinicopathological and prognostic features of DCIS-Mi with pure DCIS and IDC-T1 (invasive ductal carcinoma with a tumor size ≤2 cm) as control. We retrospectively reviewed 242 cases of DCIS-Mi, 280 cases of pure DCIS, and 347 cases of IDC-T1. The clinicopathological features, therapeutic schemes and survival status were compared among the three groups. After a median follow-up of 109 months, the 5-year disease-free survival (DFS) was lower for the DCIS-Mi patients than for the DCIS patients but higher than the IDC-T1 patients (100%, 96.89% and 87.86% respectively, P<0.001). The 5-year breast cancer specific survival for DCIS-Mi patients was also between that of DCIS and IDC-T1 patients (100%, 99.32%, and 95.42% respectively, P=0.001). Tumor size (P<0.001, HR=18.31, 95% confidence interval (CI) 5.53-60.65) was identified as an independent prognostic factor for recurrence or metastasis. Furthermore, our study indicated that DCIS-Mi patients derived minimal, if any, benefit from chemotherapy treatment after mastectomy (P=0.63, HR=1.50, 95% CI 0.29-7.87). To our knowledge, this is the largest follow-up cohort study on Chinese DCIS-Mi patients. Our data suggested that DCIS-Mi exhibited worse clinical outcome than pure DCIS but better than that of IDC-T1. Tumor size was an independent prognostic factor. Post-mastectomy chemotherapy did not help for increasing DFS for DCIS-Mi patients.}, } @article {pmid31723866, year = {2018}, author = {Kim, I and Kim, WY and Jeoung, ES and Lee, K}, title = {Current Status and Survival Impact of Infectious Disease Consultation for Multidrug-Resistant Bacteremia in Ventilated Patients: A Single-Center Experience in Korea.}, journal = {Acute and critical care}, volume = {33}, number = {2}, pages = {73-82}, pmid = {31723866}, issn = {2586-6060}, abstract = {BACKGROUND: We evaluated the current status and survival impact of infectious disease consultation (IDC) in ventilated patients with multidrug-resistant (MDR) bacteremia.

METHODS: One hundred sixty-one consecutive patients from a single tertiary care hospital were enrolled over a 5-year period. Patients with at least one of the following six MDR bacteremias were included: methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), carbapenem-resistant gram-negative rods (Acinetobacter baumannii and Pseudomonas aeruginosa), and vancomycin-resistant Enterococcus faecium.

RESULTS: Median patient age was 66 years (range, 18 to 95), and 57.8% of subjects were male. The 28-day mortality after the day of blood culture was 52.2%. An IDC was requested for 96 patients based on a positive blood culture (59.6%). Patients without IDC had significantly higher rate of hemato-oncologic diseases as a comorbidity (36.9% vs. 11.5%, P < 0.001). Patients without an IDC had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (median, 20; range, 8 to 38 vs. median, 16; range, 5 to 34, P < 0.001) and Sequential Organ Failure Assessment (SOFA) score (median, 9; range, 2 to 17 vs. median, 7; range, 2 to 20; P = 0.020) on the day of blood culture and a higher 28-day mortality rate (72.3% vs. 38.5%, P < 0.001). In patients with SOFA ≥9 (cut-off level based on Youden's index) on the day of blood culture and gram-negative bacteremia, IDC was also significantly associated with lower 28-day mortality (hazard ratio [HR], 0.298; 95% confidence interval [CI], 0.167 to 0.532 and HR, 0.180; 95% CI, 0.097 to 0.333; all P < 0.001) based on multivariate Cox regression analysis.

CONCLUSIONS: An IDC for MDR bacteremia was requested less often for ventilated patients with greater disease severity and higher 28-day mortality after blood was drawn. In patients with SOFA ≥9 on the day of blood culture and gram-negative bacteremia, IDC was associated with improved 28-day survival after blood draw for culture.}, } @article {pmid29703057, year = {2018}, author = {Xie, L and Lin, C and Zhang, H and Bao, X}, title = {Second malignancy in young early-stage breast cancer patients with modern radiotherapy: A long-term population-based study (A STROBE-compliant study).}, journal = {Medicine}, volume = {97}, number = {17}, pages = {e0593}, pmid = {29703057}, issn = {1536-5964}, mesh = {Adult ; Age Factors ; Axilla ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Cancer Survivors/*statistics & numerical data ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Mastectomy, Segmental ; Neoplasm Staging ; Neoplasms, Second Primary/*epidemiology/etiology ; Radiotherapy, Adjuvant/adverse effects/methods ; Risk Factors ; SEER Program ; Time Factors ; Young Adult ; }, abstract = {Second cancer is a leading cause of death in long-term survivors of younger early-stage breast cancer patients. To date, relationship of age, receipt of radiotherapy (RT), and estimated doses received by target organs have not yet been well elucidated. Using Surveillance, Epidemiology, and End Results database, patients aged 20 to 44, diagnosed with a first primary staging I-IIIA ipsilateral breast invasive ductal carcinoma, underwent surgery during 1988 to 2009 were identified, and those with a second malignancy at ≥1-year follow-up were analyzed to calculate cumulative incidences (CIs) of second malignancy in whole group and each subgroup. Subgroups were dichotomized by surgery type, axillary dissection, and axillary lymph node status. With a median follow-up of 11.8 years, 22,628 women including 1495 patients (6.6%) developing second malignancies (3.7% contralateral breast cancer, 2.9% non-breast second malignancies, and 0.7% high-dose site second malignancies) were identified. Three-dimensional coordinate systems with age at primary diagnosis, time after primary breast cancer diagnosis, and CI of second malignancy as 3 axes, for endpoints including all second malignancy, second primary contralateral breast cancer, and non-breast second malignancy were presented, along with the risk in RT and non-RT groups in overall group and subgroups. Five-, 10-, 15-, and 20-year all second malignancy-free survivals in RT and non-RT groups were 89.5% versus 85.4%, 80.1% versus 75.0%, 72.9% versus 67.9%, and 65.6% versus 61.8% (P < .0001). From the large national dataset, a broad visualized overview of second malignancy risk, including second contralateral breast cancer and non-breast second cancer, suggests generally beneficial therapeutic ratio for radiotherapy in young women with early-stage breast cancer.}, } @article {pmid29700276, year = {2018}, author = {Rahmani, M and Nili, F and Tabibian, E}, title = {Endometrial Metastasis from Ductal Breast Carcinoma: A Case Report with Literature Review.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {494-499}, pmid = {29700276}, issn = {1941-5923}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Endometrial Neoplasms/*secondary ; Female ; Humans ; Menorrhagia/etiology ; Middle Aged ; Uterine Hemorrhage/etiology ; }, abstract = {BACKGROUND There are few reports of breast cancer cases with uterine metastases; among them, myometrium is more frequently involved than endometrium. The majority of breast cancer metastases to endometrium are lobular type, and there have been only 5 reported cases of ductal type since 1984. Here, we describe a new case of invasive ductal carcinoma with metastases to endometrium and isolated presentation of abnormal uterine bleeding, in addition to reviewing the existing literature on other similar cases. CASE REPORT The patient was a 51-year-old Persian woman with no remarkable past medical or family history of cancer, who presented with a 6-month complaint of menorrhagia to our gynecology clinic. Diagnostic studies including trans-vaginal ultrasonography, pathological examination of endometrial curettage specimen, immunohistochemistry findings, and X-plane and magnetic resonance mammography, and breast core-needle biopsy revealed invasive ductal breast carcinoma as the origin of the endometrial metastasis. CONCLUSIONS Abnormal uterine bleeding in a premenopausal patient should alert clinicians to the possibility of secondary as well as primary neoplasms. It is necessary to differentiate a metastatic tumor from a primary one, since the treatment and prognosis are completely different.}, } @article {pmid29695771, year = {2018}, author = {Bharti, R and Dey, G and Das, AK and Mandal, M}, title = {Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.}, journal = {British journal of cancer}, volume = {118}, number = {11}, pages = {1442-1452}, pmid = {29695771}, issn = {1532-1827}, mesh = {Animals ; Antigens, CD/metabolism ; Azacitidine/pharmacology ; Breast Neoplasms/blood supply/*metabolism ; Cadherins/metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Chick Embryo ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Interleukin-6/*metabolism ; Models, Biological ; Monoamine Oxidase/*metabolism ; Neoplasm Invasiveness ; Receptors, Interleukin-6/*metabolism ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {BACKGROUND: Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.

METHODS: We employed various in-vitro and in-vivo techniques and clinical samples.

RESULTS: We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.

CONCLUSIONS: Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.}, } @article {pmid29694313, year = {2018}, author = {Vergine, M and Musella, A and Gulotta, E and Frusone, F and De Luca, A and Maceli, F and Libia, A and Benedetti Panici, P and Monti, M}, title = {Paget's disease of the male breast: case report and a point of view from actual literature.}, journal = {Il Giornale di chirurgia}, volume = {39}, number = {2}, pages = {114-117}, pmid = {29694313}, issn = {0391-9005}, mesh = {Aged ; Alzheimer Disease/complications ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms, Male/complications/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Combined Modality Therapy ; *Estrogens ; Humans ; Male ; Mastectomy ; Neoplasms, Hormone-Dependent/complications/drug therapy/*pathology/surgery ; Neoplasms, Multiple Primary/*pathology/surgery ; Nipples/*pathology ; Paget's Disease, Mammary/complications/etiology/*pathology/surgery ; *Progesterone ; Skin Ulcer/etiology ; Tamoxifen/therapeutic use ; }, abstract = {INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer.

CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications.

CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.}, } @article {pmid29694268, year = {2018}, author = {Idan, O and Halperin, E and Hameiri, B and Reifen Tagar, M}, title = {A Rose by Any Other Name? A Subtle Linguistic Cue Impacts Anger and Corresponding Policy Support in Intractable Conflict.}, journal = {Psychological science}, volume = {29}, number = {6}, pages = {972-983}, doi = {10.1177/0956797618772823}, pmid = {29694268}, issn = {1467-9280}, mesh = {Adult ; Anger/*physiology ; *Conflict, Psychological ; Female ; Humans ; Israel ; Male ; *Politics ; *Psycholinguistics ; *Warfare ; Young Adult ; }, abstract = {Given the central role of anger in shaping adversarial policy preferences in the context of intergroup conflict, its reduction may promote conflict resolution. In the current work, we drew on psycholinguistic research on the role of language in generating emotions to explore a novel, extremely subtle means of intervention. Specifically, we hypothesized that phrasing conflict-relevant policies in noun form (vs. verb form) would reduce anger and impact policy support correspondingly. Results across three experimental studies in the context of the Israeli-Palestinian conflict supported these expectations for both support for concessions (Studies 1-3) and retaliatory policies (Study 3), with reduction in anger mediating the salutary impact of noun form (vs. verb form) on policy support. These results expand our understanding of the influence of language on emotions and policies in the context of conflict and have applied relevance for conflict-resolution efforts.}, } @article {pmid29692540, year = {2018}, author = {Gupta, K and Kumaresan, M and Venkatesan, B and Chandra, T and Patil, A and Menon, M}, title = {Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.}, journal = {The Indian journal of radiology & imaging}, volume = {28}, number = {1}, pages = {123-131}, pmid = {29692540}, issn = {0971-3026}, abstract = {CONTEXT: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis.

AIMS: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade.

SETTINGS AND DESIGN: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas.

MATERIALS AND METHODS: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades.

STATISTICAL ANALYSIS USED: Chi square test, ordinal regression, and Goodman and Kruskal tau test.

RESULTS: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor (β 1.566, P 0.0001). The masses with abrupt interface boundary are more likely grade 3 (β 1.524, P 0.001) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade (β 1.146, P 0.04) as compared to masses with hypoechoic echotexture.

CONCLUSIONS: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.}, } @article {pmid29692363, year = {2018}, author = {Babaei, R and Schuster, M and Meln, I and Lerch, S and Ghandour, RA and Pisani, DF and Bayindir-Buchhalter, I and Marx, J and Wu, S and Schoiswohl, G and Billeter, AT and Krunic, D and Mauer, J and Lee, YH and Granneman, JG and Fischer, L and Müller-Stich, BP and Amri, EZ and Kershaw, EE and Heikenwälder, M and Herzig, S and Vegiopoulos, A}, title = {Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis.}, journal = {Science signaling}, volume = {11}, number = {527}, pages = {}, doi = {10.1126/scisignal.aai7838}, pmid = {29692363}, issn = {1937-9145}, support = {R01 DK090166/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; }, mesh = {Adipocytes, Beige/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/*metabolism/pathology ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; Female ; Gene Expression Profiling ; Humans ; Inflammation/*genetics/metabolism ; Janus Kinases/*genetics/metabolism ; Lipase/genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; STAT3 Transcription Factor/genetics/metabolism ; Signal Transduction/genetics ; Transforming Growth Factor beta/*genetics/metabolism ; }, abstract = {The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.}, } @article {pmid29690609, year = {2018}, author = {Shen, T and Wang, T and Sun, Y and Wu, Y and Jin, Y}, title = {On the Energy Efficiency of On-Off Keying Transmitters with Two Distinct Types of Batteries.}, journal = {Sensors (Basel, Switzerland)}, volume = {18}, number = {4}, pages = {}, pmid = {29690609}, issn = {1424-8220}, abstract = {As nodes in wireless sensor networks are usually powered by nonrenewable batteries, energy efficient design becomes critical. This paper considers a battery-powered transmitter using on-off keying (OOK) modulation and studies its energy efficiency in terms of the battery’s energy consumption for per bit transmission (BECPB). In particular, the transmitter may use one of two distinct types of batteries with battery utilization factor (BUF) depending on discharge current. The first has an instantaneous discharge current (IDC)-based BUF, while the second has a mean discharge current (MDC)-based BUF. For each type of battery, a closed-form BECPB expression is derived under a Rayleigh channel when a prescribed symbol error rate (SER) is guaranteed. Then theoretical analysis is made to study the impact of battery characteristic parameter γ , communication distance d and bandwidth B on the BECPB. Finally, the analysis is corroborated by numerical experimental results, which reveal that: the BECPB for each type of battery increases with γ and d; the BECPB for the two batteries first decreases and then increases with B, and there exists the optimal bandwidth corresponding to the minimum BECPB; the battery with IDC-based BUF corresponds to a larger BECPB. When γ and d are large, the BECPB for each type of battery is significantly higher than that for the ideal battery whose BUF is aways 1. For instance, when γ = 0.015 , d = 90 m and B = 10 kHz, the BECPB for IDC-based and MDC-based battery is nearly 60% amd 25% higher than that of the ideal battery, respectively.}, } @article {pmid29686118, year = {2018}, author = {Sheehan, J and Tate, J and Mott, R and Geer, C and Wolfe, R and Strowd, RE and Guzik, A}, title = {Pearls & Oy-sters: The critical role of histopathology in diagnosing cancer-associated necrotizing CNS vasculitis.}, journal = {Neurology}, volume = {90}, number = {17}, pages = {808-811}, doi = {10.1212/WNL.0000000000005350}, pmid = {29686118}, issn = {1526-632X}, mesh = {Aged ; Breast Neoplasms/pathology ; Carcinoma, Squamous Cell/*complications/diagnostic imaging/secondary ; Electroencephalography ; Female ; Humans ; Magnetic Resonance Imaging ; Vasculitis, Central Nervous System/*complications/diagnostic imaging ; }, abstract = {OBJECTIVE: To highlight the importance of a broad differential and histopathologic confirmation in patients with newly diagnosed cancer with brain lesions atypical for CNS metastasis.

METHODS: We report 2 cases of biopsy-proven CNS vasculitis in patients undergoing treatment for a newly diagnosed nonmetastatic cancer. Comprehensive medical record review was performed to identify the clinical presentation, representative neuroimaging, histopathologic features, and response to treatment.

RESULTS: Patient 1 presented 1 month into induction therapy of malignant vaginal squamous cell carcinoma (stage 3, T2N1M0) with acute episodic left-sided hemiparesis due to seizure activity progressing to severe encephalopathy. Imaging revealed a right frontoparietal lesion while systemic workup was unrevealing. Biopsy demonstrated necrotizing vasculitis. Patient 2 presented 6 months after diagnosis of right breast invasive ductal carcinoma (stage IIa, T2N0M0, estrogen receptor-positive, progesterone receptor-positive, human epidermal growth factor receptor-2 positive) with subacute bifrontal headaches with associated phonophobia. Imaging showed hyperintense lesions involving the right temporoparietal region and systemic workup was unrevealing. Brain biopsy showed a necrotizing vasculitis. Patient 1 was treated with methyprednisolone and plasmapheresis and patient 2 was treated with prednisone. Both patients showed complete resolution of symptoms shortly after treatment and improvement on imaging.

CONCLUSIONS: These cases highlight the importance of comprehensive evaluation of new brain lesions in patients with nonmetastatic solid tumors. Characteristics of new brain lesions in patients with cancer that should raise suspicion of diagnoses other than brain metastasis include (1) primary malignancy without regional or distant metastasis, (2) imaging without discrete mass-like enhancement, and (3) cortically based location of lesions not at the gray-white matter junction.}, } @article {pmid29679553, year = {2018}, author = {Swellam, M and El Magdoub, HM and Hassan, NM and Hefny, MM and Sobeih, ME}, title = {Potential diagnostic role of circulating MiRNAs in breast cancer: Implications on clinicopathological characters.}, journal = {Clinical biochemistry}, volume = {56}, number = {}, pages = {47-54}, doi = {10.1016/j.clinbiochem.2018.04.013}, pmid = {29679553}, issn = {1873-2933}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*blood/diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology/secondary ; Diagnosis, Differential ; Early Diagnosis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis/diagnosis/pathology ; MicroRNAs/*blood/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA, Neoplasm/*blood/metabolism ; *Up-Regulation ; Young Adult ; }, abstract = {BACKGROUND: Circulating miRNAs are stable in body fluids and resembles their levels in cancer tissue/cells. They have been expressed in many cancers among them is breast cancer. Authors aimed to investigate the expression levels of three circulating oncomiRNAs (miRNA-21, miRNA-222 and miRNA-373) in serum samples as a minimally non-invasive method for early detection of breast cancer, and study their relation with clinicopathological characters.

METHODS: MiRNAs expression levels were determined using quantitative real-time polymerase chain reaction (qPCR) in serum samples from three groups: primary breast cancer patients (n = 137), benign breast lesion patients (n = 60), and healthy individuals as control group (n = 38). Statistical analyses were carried out using SPSS.

RESULTS: Significant differences were observed between the expression levels of the studied miRNAs in the investigated groups, as their median levels were increased in breast cancer patients followed by benign group patients then the healthy individuals. MiRNA-373 reported the highest diagnostic efficacy as compared to miRNA-21 and miRNA-222 with high area under the curve (AUC equals 0.987). The relation between tested miRNAs and clinicopathological factors revealed significant difference with clinical stages and histological grades. Level of miRNA-21 and miRNA-373 were statistically significantly higher in invasive duct carcinoma (IDC) as compared to non-IDC. Similarly, their levels were increased in lymph node metastasis (P < 0.01). MiRNA-222 and miRNA-373 were significantly increased in positive PgR and positive Her-2/neu status, respectively.

CONCLUSION: Assessment of miRNAs in serum samples can be applied as minimally non-invasive markers for early detection of breast cancer, and as discriminator between different clinicopathological characters.}, } @article {pmid29678335, year = {2018}, author = {Stolfo, D and Ceschia, N and Zecchin, M and De Luca, A and Gobbo, M and Barbati, G and Gigli, M and Masè, M and Pinamonti, B and Pivetta, A and Merlo, M and Sinagra, G}, title = {Arrhythmic Risk Stratification in Patients With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {121}, number = {12}, pages = {1601-1609}, doi = {10.1016/j.amjcard.2018.02.055}, pmid = {29678335}, issn = {1879-1913}, mesh = {Adult ; Cardiomyopathy, Dilated/*epidemiology ; Death, Sudden, Cardiac/*epidemiology ; Defibrillators, Implantable/statistics & numerical data ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency/*epidemiology ; Models, Statistical ; Retrospective Studies ; Risk Assessment ; Stroke Volume ; Syncope/*epidemiology ; Tachycardia, Ventricular/*epidemiology ; Time Factors ; Ventricular Fibrillation/*epidemiology ; }, abstract = {Arrhythmic risk stratification in idiopathic dilated cardiomyopathy (IDC) remains a major concern. As the ventricles remodel in time, risk factors for arrhythmic death may change. A cohort of 710 patients with idiopathic dilated cardiomyopathy, without previous ventricular arrhythmias, was retrospectively studied to understand how risks vary in time. The primary end point was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator interventions. The prediction of the arrhythmic outcome was assessed dynamically through landmark analysis. Patients were assessed at baseline, short term (12 months, interquartile range 6 to 18), and long-term (72 months, interquartile range 60 to 84). The strongest risk predictors at each evaluation were combined in 3 multivariate models. During a median follow-up of 102 months, 80 patients (11%) experienced the primary end point. At baseline, QRS duration (p = 0.008), disease duration (p <0.001), and mitral regurgitation (p = 0.010) were significantly associated with the primary end point. The 12 months' landmark model included disease duration (p = 0.049), syncope (p = 0.005), New York Heart Association classes III and IV (p = 0.02), and indexed left ventricular end-diastolic volume (p = 0.001). Finally, the 72 months' landmark model combined the indexed left ventricular end-diastolic volume (p = 0.048), the left ventricular ejection fraction (p = 0.008), and the left atrial area (p = 0.001). All the 3 models provided a satisfactory accuracy (area under the curve ranging from 0.76 to 0.82, p <0.001). With an implantable cardioverter-defibrillator, the natural course of the disease influences the effect of arrhythmic risk factors overtime. Different predictors should be considered for the risk stratification according to the timing of assessment. Impaired left ventricular ejection fraction was significantly associated with major arrhythmias only in the long term.}, } @article {pmid29676352, year = {2018}, author = {Guleria, P and Srinivas, V and Basannar, D and Dutta, V}, title = {Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma.}, journal = {Indian journal of pathology & microbiology}, volume = {61}, number = {2}, pages = {176-180}, doi = {10.4103/IJPM.IJPM_774_16}, pmid = {29676352}, issn = {0974-5130}, mesh = {Aged ; Antibodies, Monoclonal, Murine-Derived/*immunology ; Axilla/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphangiogenesis/*physiology ; Lymphatic Metastasis/*pathology ; Lymphatic Vessels/pathology ; Mastectomy, Modified Radical ; Middle Aged ; }, abstract = {CONTEXT: Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor.

METHODS AND MATERIAL: The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed.

STATISTICAL ANALYSIS: Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, χ[2] tests and Mann-Whitney U test were used.

RESULTS: Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013).

CONCLUSIONS: D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.}, } @article {pmid29675264, year = {2018}, author = {Lämmermann, I and Terlecki-Zaniewicz, L and Weinmüllner, R and Schosserer, M and Dellago, H and de Matos Branco, AD and Autheried, D and Sevcnikar, B and Kleissl, L and Berlin, I and Morizot, F and Lejeune, F and Fuzzati, N and Forestier, S and Toribio, A and Tromeur, A and Weinberg, L and Higareda Almaraz, JC and Scheideler, M and Rietveld, M and El Ghalbzouri, A and Tschachler, E and Gruber, F and Grillari, J}, title = {Blocking negative effects of senescence in human skin fibroblasts with a plant extract.}, journal = {NPJ aging and mechanisms of disease}, volume = {4}, number = {}, pages = {4}, pmid = {29675264}, issn = {2056-3973}, support = {W 1224/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris, which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.}, } @article {pmid29674097, year = {2018}, author = {Kariminezhad, E and Elektorowicz, M}, title = {Effect of various electrokinetic treatment regimes on solids surface properties and thermal behavior of oil sediments.}, journal = {Journal of hazardous materials}, volume = {353}, number = {}, pages = {227-235}, doi = {10.1016/j.jhazmat.2018.03.060}, pmid = {29674097}, issn = {1873-3336}, abstract = {The electrokinetic process has shown its ability to separate the different material phases. However, not much is known about the effect of the electric fields on the surface properties of solids in the oil sediments and their behavior under different electrical regimes. In this study, the effect of four different types of electrical current on the surface properties of oil sediments was investigated, namely constant direct current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and decremental direct current (DDC). X-ray photoelectron spectroscopy (XPS) analyses showed a decrease in the concentration of carbon from 99% in centrifuged samples to 63% on the surface of the solids in the PDC-treated oil sediment. Wettability alteration and contact angle studies showed an enhance in hydrophilicity of the solids following electrokinetic treatment. A significant change in carbon and oxygen-containing functionalities at the surface solids of the DDC-treated sediment was also observed. Thermogravimetric analyses (TGA) confirmed the ability of electrokinetic treatment in separating the phases by shifting the thermogram profiles towards lower temperatures. The findings showed that the electrokinetic process exerts its effect by altering the surface properties of the sediment solids and destabilizing water-in-oil emulsions to facilitate phase separation of this complex waste.}, } @article {pmid29672601, year = {2018}, author = {Kassardjian, A and Shintaku, PI and Moatamed, NA}, title = {Expression of immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-L1), in female breast carcinomas.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0195958}, pmid = {29672601}, issn = {1932-6203}, mesh = {Adult ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/immunology/metabolism/pathology ; CTLA-4 Antigen/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; T-Lymphocyte Subsets/immunology/*metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining.

METHODS: Immunohistochemical staining for PD-L1 and CTLA-4 expression was performed on a tissue microarray of 102 cores, which included normal and neoplastic breast tissues. Neoplastic cores were divided into four groups: Ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and invasive tubular carcinoma (ITC). PD-L1 and CTLA-4 expressions were scored based on a system which accounted for the percentage and intensity of positivity and results provided in conjunction with available clinical and demographic data.

RESULTS: Overall, CTLA-4 was over-expressed in 49 of 93 (52.7%) breast tumors. Subcategorically, CTLA-4 was positive in 3 of 8 (37.5%) ductal carcinoma in situ, 40 of 73 (55%) of invasive ductal carcinomas, 4 of 10 (40%) of invasive lobular carcinomas and 2 of 2 (100%) of invasive tubular carcinomas. All 6 normal breast tissues were interpreted as negative for CTLA-4 staining. Only 4.1% of the invasive ductal carcinomas were positive for PD-L1 reactivity and the remaining carcinomas stained negative.

CONCLUSIONS: This study shows a significant overexpression of CTLA-4 in >50% of breast carcinomas with no such overexpression of CTLA-4 in benign breast tissues. PDL-1 staining is seen in only a small number of invasive ductal carcinomas (4.1%). These findings suggest the need for further investigation of anti-CTLA-4 and anti-PD-L1 immunotherapies and their efficacy in the treatment of breast carcinomas with overexpression of these immune modulators. In addition, the proposed scoring system will facilitate a more systematic correlation between tumor reactivity and clinical outcome which can be applied to all intracytoplasmic tumor markers.}, } @article {pmid29669935, year = {2018}, author = {Zhu, S and Ward, BM and Yu, J and Matthew-Onabanjo, AN and Janusis, J and Hsieh, CC and Tomaszewicz, K and Hutchinson, L and Zhu, LJ and Kandil, D and Shaw, LM}, title = {IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma.}, journal = {JCI insight}, volume = {3}, number = {8}, pages = {}, pmid = {29669935}, issn = {2379-3708}, support = {F31 CA206378/CA/NCI NIH HHS/United States ; R01 CA142782/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Humans ; Insulin Receptor Substrate Proteins/*genetics ; Lymph Nodes/pathology ; Middle Aged ; Mutation, Missense/genetics ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Receptor, IGF Type 1 ; Receptors, Somatomedin/*genetics ; Exome Sequencing/methods ; }, abstract = {Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC.}, } @article {pmid29668607, year = {2018}, author = {Ma, Y and Shen, J and Wang, LX}, title = {Successful treatment of high-risk myelodysplastic syndrome with decitabine-based chemotherapy followed by haploidentical lymphocyte infusion: A case report and literature review.}, journal = {Medicine}, volume = {97}, number = {16}, pages = {e0434}, pmid = {29668607}, issn = {1536-5964}, mesh = {Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Azacitidine/*analogs & derivatives/therapeutic use ; Decitabine ; Female ; HLA Antigens/administration & dosage ; Humans ; *Lymphocyte Transfusion ; Myelodysplastic Syndromes/drug therapy/*therapy ; Treatment Outcome ; }, abstract = {RATIONALE: The current therapy for elderly patients with high-risk myelodysplastic syndromes (MDSs) remains unsatisfactory. Decitabine, which has been approved to treat MDS, cannot eliminate malignant clones of MDS.

PATIENT CONCERNS: A 68-year-old woman presented with multiple divergent bleeding points in the subcutaneous tissue of the limb. Two years earlier, she had been diagnosed with invasive ductal carcinoma of the left breast and had undergone left modified radical mastectomy and local radiation therapy.

DIAGNOSES: The patient was diagnosed with MDS refractory anemia with excess of blast II and was classified as very high risk according to the revised international prognostic scoring system.

INTERVENTIONS: The chemotherapy regimen consisted of decitabine (20 mg/m intravenously on days 1-5), cytarabine (10 mg/m every 12 hours subcutaneously on days 1-5), aclarubicin hydrochloride (20 mg intravenously on days 1, 3, and 5), and recombinant human granulocyte colony-stimulating factor (250 μg/d subcutaneously from day 0 to day 5). Peripheral mononuclear cells from her son were infused at 36 hours after the end of each chemotherapy cycle. The patient received a total of 4 cycles of the therapy.

OUTCOMES: The patient achieved complete remission after the first cycle of the treatment. There was no clinical evidence of MDS relapse as of 4 years after the completion of the treatment.

LESSONS: The results suggested that decitabine-based chemotherapy and haploidentical lymphocyte infusion may be act synergistically. Combination therapy is a suitable, safe, and effective treatment regimen for elderly patients with high-risk MDS.}, } @article {pmid29667484, year = {2019}, author = {Porat, R and Tamir, M and Wohl, MJA and Gur, T and Halperin, E}, title = {Motivated emotion and the rally around the flag effect: liberals are motivated to feel collective angst (like conservatives) when faced with existential threat.}, journal = {Cognition & emotion}, volume = {33}, number = {3}, pages = {480-491}, doi = {10.1080/02699931.2018.1460321}, pmid = {29667484}, issn = {1464-0600}, mesh = {Adult ; *Anxiety ; Attitude ; *Emotions ; Fear/*psychology ; Female ; Humans ; Male ; *Motivation ; *Politics ; White People/psychology ; Young Adult ; }, abstract = {A careful look at societies facing threat reveals a unique phenomenon in which liberals and conservatives react emotionally and attitudinally in a similar manner, rallying around the conservative flag. Previous research suggests that this rally effect is the result of liberals shifting in their attitudes and emotional responses toward the conservative end. Whereas theories of motivated social cognition provide a motivation-based account of cognitive processes (i.e. attitude shift), it remains unclear whether emotional shifts are, in fact, also a motivation-based process. Herein, we propose that under threat, liberals are motivated to feel existential concern about their group's future vitality (i.e. collective angst) to the same extent as conservatives, because this group-based emotion elicits support for ingroup protective action. Within the context of the Palestinian-Israeli conflict, we tested and found support for this hypothesis both inside (Study 1) and outside (Study 2) the laboratory. We did so using a behavioural index of motivation to experience collective angst. We discuss the implications of our findings for understanding motivated emotion regulation in the context of intergroup threat.}, } @article {pmid29666097, year = {2018}, author = {Lim, GH and Tay, SPX and Gudi, M}, title = {Natural history of luminal A breast invasive ductal carcinoma in an elderly.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, pmid = {29666097}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; *Mammography ; *Sentinel Lymph Node Biopsy ; Treatment Outcome ; *Ultrasonography ; }, abstract = {An elderly woman, with no clinically palpable breast lump, presented with an initially benign-appearing lesion on ultrasound. She was followed up to reveal the natural history of luminal A breast cancer.}, } @article {pmid29665448, year = {2018}, author = {Ouldamer, L and Poisson, E and Arbion, F and Bonneau, C and Vildé, A and Body, G and Michenet, P}, title = {All pure flat atypical atypia lesions of the breast diagnosed using percutaneous vacuum-assisted breast biopsy do not need surgical excision.}, journal = {Breast (Edinburgh, Scotland)}, volume = {40}, number = {}, pages = {4-9}, doi = {10.1016/j.breast.2018.03.012}, pmid = {29665448}, issn = {1532-3080}, mesh = {Biopsy/instrumentation/methods ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology/surgery ; Calcinosis/*diagnosis/pathology ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; Hyperplasia/diagnosis ; Logistic Models ; Mammography ; Middle Aged ; Retrospective Studies ; Vacuum ; }, abstract = {BACKGROUND: The purposes of this study were to evaluate the outcome of women with pure flat atypical atypia (FEA) diagnosed at vacuum-assisted breast biopsy (VABB) targeting microcalcifications and to determine whether clinical, radiological and pathologic parameters are able to predict which lesions will be upgraded to malignancy.

MATERIALS: 2414 cases of consecutive VABB for microcalcifications using VA 8-, 10- or 11-Gauge stereotactically guided core biopsy performed between January 2005 and December 2011 from two french breast cancer centers were evaluated. Data of women with VABB-diagnosed pure FEA who underwent either excisional surgery or mammographic follow-up were analyzed. Cases with mass lesions or ipsilateral cancers were excluded. Two pathologists (FA,PM) reviewed the results of procedures performed. Clinical, radiological, as well as histological criteria have been studied in order to determine the correlation between these factors and carcinoma underestimation.

RESULTS AND CONCLUSION: This study included 70 cases of pure FEA. Twenty women underwent surgical excision and 50 had clinical and mammographic surveillance only. In three women FEA was upgraded to breast cancer on excision. Clinical and mammographic follow-up for a mean of 56 months ± 27 in the group without excision showed two cancers in the same breast (Intermediate grade DCIS, and invasive ductal carcinoma 84 and 48 months respectively after VABB). Three factors were significantly predictive of underestimation or occurence of cancer for pure FEA when the radiologic lesions are calcifications: age≥ 57 years, radiologic size >10 mm and number of FEA foci ≥4.}, } @article {pmid29661250, year = {2018}, author = {Liu, WS and Chan, SH and Chang, HT and Li, GC and Tu, YT and Tseng, HH and Fu, TY and Chang, HY and Liou, HH and Ger, LP and Tsai, KW}, title = {Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.}, journal = {Breast cancer research : BCR}, volume = {20}, number = {1}, pages = {25}, pmid = {29661250}, issn = {1465-542X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Cell Proliferation/genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Isocitrate Dehydrogenase/*genetics ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Signal Transduction/genetics ; Snail Family Transcription Factors/*genetics ; }, abstract = {BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown.

METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion.

RESULTS: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer.

CONCLUSION: Our findings revealed that a IDH1[low]/Snail[high] molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.}, } @article {pmid29657704, year = {2018}, author = {Ágoston, EI and Somorácz, Á and Madaras, L and Zaránd, A and Szentmártoni, G and Orosz, Z and Dank, M and Baranyai, Z}, title = {Successful treatment of three synchronous primary malignant tumours-reflection on surgical, pathological and oncological aspects and decision making.}, journal = {Journal of surgical case reports}, volume = {2018}, number = {4}, pages = {rjy041}, pmid = {29657704}, issn = {2042-8812}, abstract = {We report a case of a patient with triple synchronous primary malignancies (breast, colon, kidney) which has not been previously reported in the literature. A 70-year-old woman was diagnosed with invasive ductal carcinoma of the left breast with axillary lymph node metastasis. During the staging period, renal cell carcinoma on the left kidney and mucinous adenocarcinoma in the proximal colon were found. Since the breast tumour demonstrated favourable biology, aromatase inhibitor therapy had been started and simultaneous right colectomy and left nephrectomy was performed. Six months after the first diagnosis, left sector excision and axillary block dissection were performed. Adjuvant FEC chemotherapy was administered, followed by radiotherapy. During the 16-month follow-up period disease recurrence was not detected.}, } @article {pmid29655534, year = {2018}, author = {Kariminezhad, E and Elektorowicz, M}, title = {Comparison of constant, pulsed, incremental and decremental direct current applications on solid-liquid phase separation in oil sediments.}, journal = {Journal of hazardous materials}, volume = {358}, number = {}, pages = {475-483}, doi = {10.1016/j.jhazmat.2018.04.002}, pmid = {29655534}, issn = {1873-3336}, abstract = {Phase separation of oil wastes can mitigate the effects on the environment, by decreasing the volume of hazardous materials and regenerate energy. This study focused on the advanced electrokinetic method as a treatment technology to treat oil sediments from oil refineries and separate them into their individual phase components. The effects of four types of electrical field on the phase separation of oil sediments from an oil refinery were investigated namely constant direct current (CDC), pulsed direct current (PDC), incremental direct current (IDC) and decremental direct current (DDC). The results showed that the extent and quality of phase separation differed based on the type of electrical current applied, and indicated that different mechanisms such as electroosmosis, electrophoresis, electro-demulsification, and electro-sedimentation might have been involved in the separation process depending on the type of electrical supply. The application of DDC and IDC was found to cause a significant separation of solids by electrophoresis with the movement of almost 70% of solids to the anode of the reactors. The DDC and IDC regimes resulted in the most efficient phase separation of the oil sediments, and even incurred a highly resolved separation of light hydrocarbons at the top anode.}, } @article {pmid29650929, year = {2018}, author = {Ishiba, T and Oda, G and Nakagawa, T and Akashi, T and Yamashita, Y and Aburatani, T and Ogo, T and Nakashima, Y and Baba, H and Hoshino, N and Nishioka, Y and Kawano, T}, title = {[A Case of HER2 Positive Occult Breast Cancer Presenting as Swollen Axillary Lymph Nodes].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {3}, pages = {533-535}, pmid = {29650929}, issn = {0385-0684}, mesh = {Aged ; Axilla ; Breast Neoplasms/chemistry/*diagnosis/pathology/surgery ; *Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology/surgery ; Receptor, ErbB-2/analysis ; Treatment Outcome ; }, abstract = {Occult breast cancer, which develops as a metastatic lesion with no primary tumor detected in the breast, is a rare breast cancer. A 68-year-old female patient particularly complained of the presence of a right axillary mass. The mass in the right axilla was palpable, but no tumor was found in both the breasts on palpation, ultrasound examination, or MRI. Partial breast resection and axillary lymph node dissection were performed following a diagnosis of invasive ductal carcinoma by core needle biopsy. There was no mammary gland tissue present around the tumor due to the pathology of the disease, and the tumor was diagnosed as occult breast cancer. As the cancer was ER negative and HER2 positive, treatment with a combination of FEC, docetaxel, and trastuzumab was initiated. Radiotherapy, which irradiated the right supraclavicular fossa and the right mammary gland, was administered. No disease recurrence and mammary tumor has been reported in the patient till date. Treatment of occult breast cancer generally includes local therapy such as radiation and surgery. However, in the present case, we did not operate upon the breast; instead we treated the right breast and the right supraclavicular fossa with radiation therapy. As the tumor was HER2 positive, we reasoned that local control of disease would be likely if treatment with chemotherapy and trastuzumab was performed effectively.}, } @article {pmid29650905, year = {2018}, author = {Fujimoto, Y and Yamaguchi, K and Ueno, A and Sakurai, R and Nagahisa, Y and Imai, S and Kawamoto, K}, title = {[A Case of HER2-Positive Breast Cancer with Liver Metastases Showing Three Years of Complete Response to Combination Therapy with Trastuzumabplus Pertuzumab].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {3}, pages = {459-461}, pmid = {29650905}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Middle Aged ; Receptor, ErbB-2/analysis ; Recurrence ; Trastuzumab/administration & dosage ; }, abstract = {A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control.}, } @article {pmid29650835, year = {2018}, author = {Hirano, T and Suzuki, S and Adachi, K and Kubota, H and Hara, Y and Enomoto, K and Tomita, R and Fujisaki, S and Sakurai, K}, title = {[Diagnosis of a Non-Invasive Ductal Carcinoma, Assisted by Long-Term Follow-Up of Spontaneous Nipple Discharge - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {4}, pages = {685-687}, pmid = {29650835}, issn = {0385-0684}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging ; Female ; Follow-Up Studies ; Humans ; Nipple Discharge ; Sentinel Lymph Node Biopsy ; Time Factors ; }, abstract = {We report a case of a non-invasive ductal carcinoma revealed on long-term follow-up of spontaneous nipple discharge. The patient, a 36-year-old woman, had noticed spontaneous nipple discharge from both breasts over a 3-year period. Mammography and ultrasonography did not reveal any lesions in the breasts. The nipple discharge from her left breast stopped 36 months after initial clinical assessment. However, the nipple discharges from her right breast transformed into a bloody discharge from a single duct. Ultrasonography showed a tumor, 6mm in diameter, in the upper-outer quadrant of her right breast. A core needle biopsy for breast tumor led to a pathological diagnosis of non-invasive ductal carcinoma. We conducted a whole-body clinical examination but no metastatic lesions were detected. Subsequently, we performed breastconserving surgery and sentinel lymph node biopsy. The pathological diagnosis was non-invasive ductal carcinoma in situ. The tumor was positive for estrogen and progesterone receptors, but negative for HER2/neu. The Ki-67 labeling index was 5%. The surgical margin was negative. We diagnosed the tumor as TisN0M0=Stage 0. Endocrine therapy comprising tamoxifen (20mg/day)was initiated. Four years after surgery, she was well without any metastases.}, } @article {pmid29650825, year = {2018}, author = {Kubota, H and Adachi, K and Suzuki, S and Fujisaki, S and Hara, Y and Enomoto, K and Tomita, R and Hirano, T and Sakurai, K}, title = {[Successful Breast Conserving Surgery for Simultaneous and Ipsilateral Multiple Breast Carcinomas of Young Patient - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {4}, pages = {655-657}, pmid = {29650825}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mammography ; Margins of Excision ; *Mastectomy, Segmental ; Tamoxifen/therapeutic use ; }, abstract = {We report a case of a simultaneous and ipsilateral multiple breast carcinoma.The patient was 35-year-old woman.She was noticed a breast lump on her right breast, and visited our hospital.Mammography showed a tumor accompanied by spiculation on her right breast.Ultrasonography revealed 2 tumors with irregular margins, 23mm in diameter and 12mm in diameter, and were observed on C area of her right breast.The continuity of the 2 tumors was not clear.Core needle biopsies for each breast tumors led to a diagnosis.The pathological diagnosis was invasive ductal carcinoma.We checked up whole body. There was no metastatic lesion.We performed breast conserving surgery and sentinel node biopsy.The pathological diagnosis was invasive ductal carcinoma, positive for estrogen receptor and progesterone receptor, negative for HER2/neu.The Ki-67 positive cell index was 30%.The surgical margin was negative.We diagnosed T2N0M0=Stage II A.She was started the endocrine therapy by LH-RH agonist and tamoxifen.Four years after surgery, she was well without metastases.}, } @article {pmid29633909, year = {2018}, author = {Widiana, HS and Simpson, K and Manderson, L}, title = {Cultural expressions of depression and the development of the Indonesian Depression Checklist.}, journal = {Transcultural psychiatry}, volume = {55}, number = {3}, pages = {339-360}, doi = {10.1177/1363461518764491}, pmid = {29633909}, issn = {1461-7471}, mesh = {Adult ; Checklist ; *Depression/diagnosis/ethnology/physiopathology ; *Depressive Disorder/diagnosis/ethnology/physiopathology ; Humans ; Indonesia/ethnology ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*methods/standards ; }, abstract = {Depression may manifest differently across cultural settings, suggesting the value of an assessment tool that is sensitive enough to capture these variations. The study reported in this article aimed to develop a depression screening tool for Indonesians derived from ethnographic interviews with 20 people who had been diagnosed as having depression by clinical psychologists at primary health centers. The tool, which we have termed the Indonesian Depression Checklist (IDC), consists of 40 items. The tool was administered to 125 people assessed to have depression by 40 clinical psychologists in primary health centers. The data were analyzed with Confirmatory Factor Analysis (CFA) (IBM SPSS AMOS Software). CFA identified a five-factor hierarchical model (χ [2] = 168.157, p = .091; CFI = .963; TLI = .957; RMSEA = .036). A 19-item inventory of the IDC, with five factors - Physical Symptoms, Affect, Cognition, Social Engagement and Religiosity - was identified. There was a strong correlation between the total score of the IDC and total score of the Center for Epidemiological Studies-Depression scale (revised version CES-D), a standard tool for assessing symptoms of depression. The IDC accommodates culturally distinctive aspects of depression among Indonesians that are not included in the CES-D.}, } @article {pmid29628124, year = {2018}, author = {Chen, X and Ding, B and Zhang, P and Geng, S and Xu, J and Han, B}, title = {Intraductal carcinoma of the prostate: What we know and what we do not know.}, journal = {Pathology, research and practice}, volume = {214}, number = {5}, pages = {612-618}, doi = {10.1016/j.prp.2018.03.003}, pmid = {29628124}, issn = {1618-0631}, mesh = {Biopsy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*pathology ; Diagnosis, Differential ; Humans ; Male ; Neoplasm Grading/methods ; Prostate/pathology ; Prostatic Neoplasms/*diagnosis/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is a malignant, clonal proliferation of cells growing within the basement membrane-bound structures of the prostate. IDC-P is usually associated with unfavorable clinicopathologic parameters such as large tumor volume, high-grade Gleason score, extra prostatic extension and seminal vesicle invasion. Majority of laboratory and patient data suggest that IDC-P represents intraductal spread of invasive carcinoma, rather than a precursor lesion. Additionally, relationship of IDC-P and adjacent invasive carcinoma has been investigated in a series of molecular studies. The differential diagnosis of IDC-P from other lesions is critical for patient management. In this article, we summarize current literatures regarding what we know about IDC-P, including its pathological morphology, incidence, differential diagnosis, molecular features and clinical significance. In addition, we propose several issues that we currently do not know about IDC-P. Further research is needed to better understand the biological nature of IDC-P.}, } @article {pmid29624807, year = {2018}, author = {van der Spek, N and Jansen, F and Holtmaat, K and Vos, J and Breitbart, W and van Uden-Kraan, CF and Tollenaar, RAEM and Cuijpers, P and Coupé, VMH and Verdonck-de Leeuw, IM}, title = {Cost-utility analysis of meaning-centered group psychotherapy for cancer survivors.}, journal = {Psycho-oncology}, volume = {27}, number = {7}, pages = {1772-1779}, pmid = {29624807}, issn = {1099-1611}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Cancer Survivors/*psychology ; Cost-Benefit Analysis ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*economics/psychology/*therapy ; Psychotherapy/economics ; Psychotherapy, Group/economics/*methods ; Quality of Life/*psychology ; Quality-Adjusted Life Years ; Self Concept ; Self-Help Groups/economics ; Watchful Waiting ; }, abstract = {BACKGROUND: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) improves meaning, psychological well-being, and mental adjustment to cancer and reduces psychological distress. This randomized controlled trial was conducted to investigate the cost-utility of MCGP-CS compared with supportive group psychotherapy (SGP) and care-as-usual (CAU).

METHODS: In total, 170 patients were randomized to MCGP-CS, SGP, or CAU. Intervention costs, direct medical and nonmedical costs, productivity losses, and health-related quality of life were measured until 6 months follow-up, using the TIC-P, PRODISQ, data from the hospital information system, and the EQ-5D. The cost-utility was calculated by comparing mean cumulative costs and quality-adjusted life years (QALYs).

RESULTS: Mean total costs ranged from €4492 (MCGP-CS) to €5304 (CAU). Mean QALYs ranged .507 (CAU) to .540 (MCGP-CS). MCGP-CS had a probability of 74% to be both less costly and more effective than CAU, and 49% compared with SGP. Sensitivity analyses showed these findings are robust. If society is willing to pay €0 for one gained QALY, MCGP-CS has a 78% probability of being cost-effective compared with CAU. This increases to 85% and 92% at willingness-to-pay thresholds of €10 000 and €30 000, which are commonly accepted thresholds.

CONCLUSIONS: MCGP-CS is highly likely a cost-effective intervention, meaning that there is a positive balance between the costs and gains of MCGP-CS, in comparison with SGP and CAU.}, } @article {pmid29624211, year = {2018}, author = {Wald, N and Carthy, T and Shenaar-Golan, V and Tadmor-Zisman, Y and Ziskind, M}, title = {Influence of maternal negative emotion reactivity and cognitive reappraisal on child anxiety disorder.}, journal = {Depression and anxiety}, volume = {35}, number = {4}, pages = {353-359}, doi = {10.1002/da.22745}, pmid = {29624211}, issn = {1520-6394}, mesh = {Adolescent ; Adult ; Affective Symptoms/*psychology ; Anxiety Disorders/*psychology ; Child ; Child of Impaired Parents/*psychology ; Female ; Humans ; Male ; Middle Aged ; Mothers/*psychology ; Self-Control/*psychology ; }, abstract = {BACKGROUND: Anxiety disorders are among the most common psychopathologies in childhood. Two underlying contributors to child anxiety disorders (ADs) are negative emotional hyper-reactivity and deficits in reappraisal, a cognitive strategy of emotion regulation. Given that emotion regulation develops in the context of parent-child interaction, the aim of this study was to fill a research gap regarding the association between maternal negative emotional reactivity (NER) and reappraisal and child anxiety by examining (a) whether mothers of children with ADs display abnormalities in emotional reactivity and reappraisal compared to mothers of children without ADs; (b) whether maternal NER and reappraisal are associated with child anxiety; and (c) whether maternal reactivity and reappraisal significantly explain the variance in the level of child anxiety beyond the level of maternal anxiety.

METHOD: Forty-nine mothers and their AD children (aged 10-17) were assessed at admission to an anxiety disorder clinic and were compared to a control group of 42 mothers and their non-anxious (NA) children. Child and maternal anxiety were assessed, as well as maternal NER and reappraisal.

RESULTS: Mothers of AD children showed a higher NER as well as reappraisal deficits compared to the control group. Self-rated child anxiety was associated with maternal deficits in reappraisal. The variance in child anxiety was significantly explained by the level of maternal anxiety as well as maternal reappraisal deficits.

CONCLUSIONS: This study suggests that maternal NER and reappraisal play an important role in child anxiety and should be considered in prevention and intervention of childhood ADs.}, } @article {pmid29623677, year = {2018}, author = {Morrow, E and Lannigan, A and Doughty, J and Litherland, J and Mansell, J and Stallard, S and Mallon, E and Romics, L}, title = {Population-based study of the sensitivity of axillary ultrasound imaging in the preoperative staging of node-positive invasive lobular carcinoma of the breast.}, journal = {The British journal of surgery}, volume = {105}, number = {8}, pages = {987-995}, doi = {10.1002/bjs.10791}, pmid = {29623677}, issn = {1365-2168}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/*diagnostic imaging/pathology ; Biopsy/methods ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnostic imaging/pathology ; Middle Aged ; Neoplasm Staging ; Preoperative Care/methods ; Prospective Studies ; Scotland ; Sensitivity and Specificity ; Ultrasonography/*methods ; }, abstract = {BACKGROUND: Preoperative staging of the axilla is important to allow decisions regarding neoadjuvant treatment and the management of the axilla. Invasive lobular carcinoma metastases are difficult to detect because of the infiltrative pattern of the nodal spread. In this study the sensitivity of preoperative axillary staging between invasive lobular (ILC) and ductal (IDC) carcinoma was compared.

METHODS: All women diagnosed with pure ILC or IDC in the West of Scotland in 2012-2014 were identified from a database maintained prospectively within the Managed Clinical Network. Pretreatment axillary ultrasound imaging (AUS), core biopsy and fine-needle aspiration cytology (FNAC) results were compared between ILC and IDC.

RESULTS: Some 602 women with ILC and 4199 with IDC had undergone axillary surgery, of whom 209 and 1402 respectively had nodal metastases. Pretreatment AUS sensitivity was significantly lower in ILC than in IDC (32·1 versus 50·1 per cent respectively, P < 0·001; OR 0·47, 95 per cent c.i. 0·34 to 0·64). Core biopsy had equally high sensitivity of 86 per cent in both subtypes; however, FNAC was significantly less sensitive in both ILC (55 per cent; P = 0·003) and IDC (75·6 per cent; P = 0·006). Multivariable analysis revealed that cT3-4 status and symptomatic presentation were both significant in predicting nodal metastasis in patients with ILC and false-negative AUS findings (OR 3·77, 95 per cent c.i. 1·69 to 8·42, P = 0·001; and OR 1·92, 1·24 to 2·98, P = 0·003, respectively).

CONCLUSION: AUS is inferior in detecting axillary node metastasis in ILC compared with IDC. Women with cT3-4 lobular carcinoma may benefit from ultrasound-guided axillary biopsy regardless of the ultrasonographic appearance of the nodes.}, } @article {pmid29622044, year = {2018}, author = {Chen, YL and Gao, Y and Chang, C and Wang, F and Zeng, W and Chen, JJ}, title = {Ultrasound shear wave elastography of breast lesions: correlation of anisotropy with clinical and histopathological findings.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {18}, number = {1}, pages = {11}, pmid = {29622044}, issn = {1470-7330}, support = {81627804//National Natural Science Foundation of China/ ; 20174Y0011//Shanghai Municipal Commission of Health and Family Planning/ ; }, mesh = {Adult ; Aged ; Anisotropy ; Breast Neoplasms/*diagnostic imaging/pathology ; Elasticity Imaging Techniques/methods/*standards ; Female ; Humans ; Middle Aged ; Reproducibility of Results ; Ultrasonography, Mammary/methods/*standards ; }, abstract = {BACKGROUND: Ultrasound shear-wave elastography (SWE) may increase specificity of breast lesion assessment with ultrasound, but elasticity measurements may change with transducer orientation, defined as anisotropy. In this study, we aimed to observe the anisotropy of SWE of breast lesions, and its correlation with clinical and histopathological findings.

METHODS: This retrospective study was approved by institutional review board. From June 2014 to June 2015, a total of 276 women (mean age, 48.75 ± 12.12 years) with 276 breast lesions (174 malignant, 102 benign) were enrolled for conventional ultrasound and SWE before surgical excision. Elasticity modulus in the longest diameter and orthogonal diameter were recorded, including maximum elasticity (Emax), mean elasticity (Emean), standard deviation (Esd) and ratio between mean elasticity of lesion and normal fatty tissue (Eratio). Anisotropy coefficients including anisotropic difference (AD) and anisotropy factors (AF) were calculated, and correlations with malignancy, tumor size, palpability, movability, lesion location and histopathology were analyzed.

RESULTS: The average Emax, Emean, Esd and Eratio of the longest diameter were significantly higher than orthogonal diameter (P < 0.05). AUCs of ADs and AFs were inferior to quantitative parameters (P < 0.001), with AUCs of AFs superior to ADs (P < 0.001). ADs showed no significant correlation with malignancy, palpability, movability, distance from nipple and skin, and histopathological patterns. ADmean was significantly higher in inner half than outer half of the breast (P = 0.034). Higher AFs were significantly correlated with larger lesion size (P = 0.042), palpability (P < 0.05), shorter distance from nipple and skin (P < 0.05) and higher suspicion for malignancy (P < 0.001). AFs were significantly higher in IDC than DCIS (P < 0.05), higher in Grade II/III than Grade I IDC (P < 0.001), and correlated with ER/PR(+) (P < 0.05).

CONCLUSIONS: AF of SWE was an indicator for malignancy and more aggressive breast cancer.}, } @article {pmid29621999, year = {2018}, author = {Balekouzou, A and Yin, P and Bekolo, CE and Pamatika, CM and Djeintote, M and Nambei, SW and Ba-Mpoutou, B and Mandjiza, DR and Shu, C and Yin, M and Qing, T and Koffi, B}, title = {Histo-epidemiological profile of breast cancers among women in the Central African Republic: about 174 cases.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {387}, pmid = {29621999}, issn = {1471-2407}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Central African Republic/epidemiology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Public Health Surveillance ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide and leading cause of cancer deaths indeveloping countries. There is very limited data on BC in the Central African Republic. The purpose of this study was to describe the epidemiological and histopathological characteristics of BC in Bangui.

METHODS: This retrospective study reviewed cancer data registries and medical records from the Pathology Unit of the National Laboratory in Bangui and the General Surgery and Gyneacology service from 2003 to 2015. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods.

RESULTS: In total, 174 cases of BC were recorded, with an average annual frequency of13.4 cases per year. The age of the women at diagnosis varied from 16 to 90 years with a median of 45.5 years and InterQuartile range (IQR) 18 years. The age group of 45-54 years represented the majority of the study population (n = 51, 29.3%).About 25.9%ofthe patients were non-educated and 85.6% lived in cities. Over 48 % of the women were housewives with a moderate economic status (n = 99, 56.9%). Sixty nine percent of the specimens received at the pathology unit were pieces of breast tumour. Invasive ductal carcinoma (n = 113, 64.9%) was the main histological form and most of the tumours were of Grade III (n = 14, 46.7%). The only imaging assessment was ultrasound performed in (n = 53, 30.4%) women. Surgery was performed in (n = 166, 95.4%) patients, while (n = 159, 91.4%) received complementary chemotherapy. At the end of the study, 84.5%of the cases had died, 12.1% were alive and 3.4% were considered "lost to follow-up".

CONCLUSION: BC is an important public health problem and affected most of the younger Central African women. Epidemiological and histological characteristics are more or less common to those described other developing countries. It is imperative to improve the awareness of health care institutions and women on the burden of BC, to carry out early screening of BC, and to strengthen the capacity of women's health care system.}, } @article {pmid29621845, year = {2018}, author = {Gilbert, B and Naidoo, TL and Redwig, F}, title = {Ins and outs of urinary catheters.}, journal = {Australian journal of general practice}, volume = {47}, number = {3}, pages = {132-136}, doi = {10.31128/AFP-10-17-4362}, pmid = {29621845}, issn = {2208-7958}, mesh = {Catheter-Related Infections/nursing/prevention & control ; Clinical Competence/standards ; Humans ; Urinary Catheterization/*adverse effects/*standards/trends ; Urinary Catheters/adverse effects/standards/trends ; }, abstract = {BACKGROUND: Inserting an indwelling catheter (IDC) is a common medical procedure that is often performed poorly and inappropriately, and can lead to significant morbidity. Although most catheterisations are performed by nursing staff, medical personnel need to be aware of the procedure, products and common IDC complications.

OBJECTIVE: Current guidelines and literature were reviewed to outline catheterisation indications, catheter types and provide a general understanding of complications associated with IDCs for&nbsp;the general practitioner (GP).

DISCUSSION: There is evidence that IDCs are often used when not indicated and improperly managed when inserted. IDCs can cause significant morbidity, prolong hospital stay and increase healthcare costs. Infection and traumatic insertion are common complications; advances in catheter design have helped to limit these complications. Most complications are avoidable, do not require specialist input and can be managed by community nurses or GPs. Reviewing indications, adopting proper technique for insertion and defining management strategies can limit complications.}, } @article {pmid29621776, year = {2018}, author = {Weigand, T and Singler, B and Fleming, T and Nawroth, P and Klika, KD and Thiel, C and Baelde, H and Garbade, SF and Wagner, AH and Hecker, M and Yard, BA and Amberger, A and Zschocke, J and Schmitt, CP and Peters, V}, title = {Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {46}, number = {2}, pages = {713-726}, doi = {10.1159/000488727}, pmid = {29621776}, issn = {1421-9778}, mesh = {Animals ; Anserine/analysis/chemistry/metabolism ; Carnosine/analysis/*chemistry/*metabolism ; Cell Line ; Cell Survival/drug effects ; Chromatography, High Pressure Liquid ; Glutathione/analysis ; Glutathione Peroxidase/genetics/metabolism ; Glycation End Products, Advanced/chemistry/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Membrane Transport Proteins/metabolism ; Mice ; Oxidative Stress/drug effects ; Peptide Transporter 1/genetics/metabolism ; Podocytes/cytology/drug effects/metabolism ; Polymers/*chemistry/metabolism ; Pyruvaldehyde/*chemistry/toxicity ; Serum Albumin/chemistry ; Superoxide Dismutase/genetics/metabolism ; Symporters/genetics/metabolism ; }, abstract = {BACKGROUND/AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo.

METHODS: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC.

RESULTS: In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143±13%, p<0.001) and tubular cells (129±3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells.

CONCLUSION: While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.}, } @article {pmid29619374, year = {2018}, author = {Oloomi, M and Moazzezy, N and Bouzari, S}, title = {Modulation of Molecular Biomarker Expression in Response to Chemotherapy in Invasive Ductal Carcinoma.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {7154708}, pmid = {29619374}, issn = {2314-6141}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/*metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; }, abstract = {Breast cancer (BC) has varied morphological and biological features and is classified based on molecular and morphological examinations. Molecular classification of BC is based on biological gene-expression profiling. In this study, biomarker modulation was assessed during BC treatment in 30 previously untreated patients. Heterogeneity among patients was pathologically diagnosed and classified into luminal and basal-like immunohistochemical profiles based on estrogen, progesterone, and human epidermal growth factor receptor (ER/PR/HER2) status. Marker heterogeneity was compared with mRNA biomarker expression in patients with BC before and after therapy. Reverse transcription-polymerase chain reaction was performed for molecular characterization. Expression and modulation of biological markers, CK19, hMAM, CEA, MUC, Myc, Ki-67, HER2/neu, ErbB2, and ER, were assessed after treatment, where the expression of the biomarkers CK19, Ki-67, Myc, and CEA was noted to be significantly decreased. Marker expression modulation was determined according to different stages and pathological characteristics of patients; coexpression of three markers (CK19, Ki-67, and Myc) was specifically modulated after therapy. In the histopathologically classified basal-like group, two markers (CK19 and Ki-67) were downregulated and could be considered as diagnostic biomarkers. In conclusion, pathological characteristics and marker variation levels can be evaluated to decide a personalized treatment for patients.}, } @article {pmid29608708, year = {2018}, author = {Young, HML and March, DS and Graham-Brown, MPM and Jones, AW and Curtis, F and Grantham, CS and Churchward, DR and Highton, P and Smith, AC and Singh, SJ and Bridle, C and Burton, JO}, title = {Effects of intradialytic cycling exercise on exercise capacity, quality of life, physical function and cardiovascular measures in adult haemodialysis patients: a systematic review and meta-analysis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {33}, number = {8}, pages = {1436-1445}, doi = {10.1093/ndt/gfy045}, pmid = {29608708}, issn = {1460-2385}, support = {CS-2013-13-014/DH_/Department of Health/United Kingdom ; DRF-2016-09-015/DH_/Department of Health/United Kingdom ; }, mesh = {Blood Pressure/*physiology ; Cardiovascular Diseases/epidemiology/*physiopathology ; Comorbidity/trends ; Exercise Tolerance/*physiology ; Humans ; Kidney Failure, Chronic/*epidemiology/physiopathology/therapy ; Pulse Wave Analysis ; *Quality of Life ; *Renal Dialysis ; }, abstract = {BACKGROUND: Intradialytic cycling (IDC), delivered during haemodialysis (HD), has the potential to improve many health issues. This systematic review and meta-analysis examine the evidence on the effects of IDC on exercise capacity, quality of life (QoL), physical function and cardiovascular health.

METHODS: Twenty-four databases were searched alongside Internet and hand searching, and consultation with experts. Eligibility criteria were cluster randomized, randomized and quasi-randomized controlled trials (RCTs) of IDC versus usual care in prevalent adult HD patients. Primary outcome measures were exercise capacity (VO2 peak and field tests) and QoL. Secondary measures were cardiac and physical function.

RESULTS: Thirteen RCTs were eligible. Eight provided data for use in meta-analyses, which indicated no significant change in VO2 peak (mean difference, MD 1.19 mL/kg/min, 95% confidence interval -1.15 to 3.52, P = 0.3), physical (mean change, MC 1.97, -8.27 to 12.22, P = 0.7) or mental component (MC 3.37, -7.94 to 14.68, P = 0.6) summary scores of the Medical Outcomes Short Form 36, pulse wave velocity (MD -0.57 m/s, -1.55 to 0.41, P = 0.4), systolic (MD -2.28 mmHg, -14.46 to 9.90, P = 0.7) or diastolic blood pressure (MD 2.25 mmHg, -3.01 to 7.50, P = 0.4) following IDC. IDC, however, leads to an improvement in performance on the 6-min walk test (MD 87.84 m, 39.60-136.09, P = 0.0004). All included studies were considered to have high risk of bias.

CONCLUSIONS: There is insufficient evidence demonstrating whether cycling exercise during HD improves patient outcomes. High-quality, adequately powered RCTs of IDC are required.}, } @article {pmid29607235, year = {2018}, author = {Kojima, N and Yamasaki, Y and Koh, H and Miyashita, M and Morita, H}, title = {Long-Acting Luteinizing Hormone-Releasing Hormone Agonist for Ovarian Hyperstimulation Induced by Tamoxifen for Breast Cancer.}, journal = {Case reports in obstetrics and gynecology}, volume = {2018}, number = {}, pages = {4931852}, pmid = {29607235}, issn = {2090-6684}, abstract = {Tamoxifen treatment for breast cancer may induce ovarian cysts and supraphysiological levels of serum estrogen. We report successful management with luteinizing hormone-releasing hormone (LHRH) agonist of ovarian hyperstimulation induced by tamoxifen. A 49-year-old woman was operated on for invasive ductal carcinoma of the right breast. She received breast irradiation and adjuvant tamoxifen therapy. After 2 years, she had a cystic ovarian mass, and her serum concentration of estradiol was 1280 pg/mL. She was treated with an injection of 11.25 mg leuprolide acetate, a long-acting LHRH agonist, without abandoning tamoxifen therapy. The levels of estradiol decreased to <10 pg/mL and the cystic mass disappeared 2 months later. Three-month depot treatment with LHRH agonists can be useful for patients receiving tamoxifen for breast cancer who have ovarian cysts and supraphysiological levels of estrogen.}, } @article {pmid31938331, year = {2018}, author = {Kim, Y and Kim, HS and Do, SI}, title = {Low nuclear zinc finger and BTB domain containing 7A expression is an independent prognostic factor for recurrence-free survival in invasive ductal carcinoma of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {11}, number = {4}, pages = {2193-2200}, pmid = {31938331}, issn = {1936-2625}, abstract = {The role of zinc finger and BTB domain containing 7A (ZBTB7A) in oncogenesis has been shown to be context-dependent, participating in pro-oncogenic or oncosuppressive mechanisms by directly regulating gene transcription or by interacting with other regulatory proteins. Alterations in ZBTB7A expression have been associated with worse prognosis. We examined ZBTB7A protein expression in breast carcinoma tissue samples and analyzed its clinical and prognostic significance. Tissue microarray blocks from 196 cases of invasive ductal carcinoma (IDC) were immunostained and <65% positively stained tumor cell nuclei were defined as low ZBTB7A expression. Of 196 IDC cases, 120 (61.2%) showed low ZBTB7A expression. Low nuclear ZBTB7A expression was associated with larger tumor size, higher histological grade, estrogen receptor negativity, progesterone receptor negativity, triple negativity, and recurrence. Cytoplasmic ZBTB7A expression was not associated with any clinicopathological characteristics. In univariate survival analysis, nuclear ZBTB7A expression did not affect overall or recurrence-free survival. However, multivariate survival analysis revealed that ZBTB7A independently predicted recurrence-free survival of IDC patients. Reduced ZBTB7A expression is associated with aggressive oncogenic behavior of IDC. ZBTB7A expression may be a novel prognostic biomarker for predicting recurrence-free survival of IDC patients.}, } @article {pmid31938320, year = {2018}, author = {Jin, X and Yu, D and Guo, C and Gong, X and Li, N and Zhao, Y}, title = {Metaplastic breast carcinoma: a clinical analysis of 26 cases.}, journal = {International journal of clinical and experimental pathology}, volume = {11}, number = {4}, pages = {2112-2117}, pmid = {31938320}, issn = {1936-2625}, abstract = {Metaplastic breast carcinoma (MBC) is a rare and aggressive neoplasm. Morphologically, it is characterized by the presence of multiple cellular differentiation and heterologous elements (squamous cells, spindle cells, cartilage or bone, etc). The clinical significance, prognostic risk factors and optimal treatment modalities of MBC are limited. This study collected clinical and pathological data of 26 MBC cases in the First Affiliated Hospital of Bengbu Medical College from July 2002 to July 2012 and investigated the clinicopathological features and the prognosis data. All patients were females aged 34-76 years old. Median tumor size was 3.5 cm and 88.5% patients were triple-negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). MBC is associated with a poor prognosis compared with conventional invasive ductal carcinoma (IDC). In our study, 5-year Overall Survival (OS) rate and 5-year Disease-Free Survival (DFS) rate were 61.5% and 53.8% respectively. Most patients in this series had high-grade, triple-negative tumors and were treated with optimal therapy.}, } @article {pmid29603326, year = {2018}, author = {Trinh, VQ and Sirois, J and Benzerdjeb, N and Mansoori, BK and Grosset, AA and Albadine, R and Latour, M and Mes-Masson, AM and Hovington, H and Bergeron, A and Ladouceur, M and Fradet, Y and Saad, F and Trudel, D}, title = {The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer-specific survival.}, journal = {The Prostate}, volume = {78}, number = {10}, pages = {697-706}, doi = {10.1002/pros.23513}, pmid = {29603326}, issn = {1097-0045}, mesh = {Aged ; Carcinoma, Intraductal, Noninfiltrating/*mortality/*pathology/surgery ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*mortality/*pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*mortality/*pathology/surgery ; Retrospective Studies ; Time Factors ; }, abstract = {BACKGROUND: To investigate the effect of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens in the context of the site of recurrence, time to recurrence, and cancer-specific survival in two academic cohorts of locally, regionally, or distantly recurrent prostate cancer.

METHODS: Our cohort included men enrolled into two academic tissue repositories from 1993 to 2011, who were treated with first-line RP who later experienced local recurrence, regional recurrence, or distant metastasis (together termed clinical recurrence, CR). RP material was reviewed to identify IDC-P and to update grading to current standards. The primary endpoint was the initial location of CR. Secondary endpoints included time to CR and cancer-specific survival. Pearson's chi-square, Welch's t-test, Mann-Whitney U test and Fisher's exact test were performed for univariate analyses. Multinomial logistic regression was used for multivariate analyses. Cancer-specific survival was analyzed with the generalized Wilcoxon test and Cox regression.

RESULTS: Eighty-five patients with CR were included in the analysis. IDC-P was present in 78.5% of patients from Center 1 and 70.0% from Center 2 (P = 0.547). IDC-P was independently associated with distant metastasis at initial CR (multivariate odds ratio = 6.27, P = 0.015). IDC-P status did not affect time to recurrence; median survival without recurrence was at 53 months for IDC-P(+) and at 50 months for IDC-P(-) (P = 0.441). Distant metastases at the initial CR event had a 36% reduction of cancer-specific survival compared to local recurrences (P = 0.007). Additionally, prostatic-bed radiotherapy (adjuvant or salvage for biochemical recurrence before distant metastasis) was associated with a 25% reduction in cancer-specific mortality compared to no radiotherapy (P = 0.023). Similar reduction in cancer-specific mortality was observed in the subgroup of patients with distant metastasis and IDC-P when treated with radiotherapy (29%, P = 0.050).

CONCLUSIONS: In our cohort, presence of IDC-P was an independent factor for distant metastasis at initial CR, but did not have a significant impact on time to CR. Furthermore, metastatic patients showed statistically reduced cancer-specific mortality when treated with radiotherapy. This reduction in cancer-specific mortality was also identified in patients with IDC-P. Future large scale validation studies should take into account the presence of IDC-P and confirm its impact on disease progression.}, } @article {pmid29602724, year = {2019}, author = {Grimm, LJ and Saha, A and Ghate, SV and Kim, C and Soo, MS and Yoon, SC and Mazurowski, MA}, title = {Relationship between Background Parenchymal Enhancement on High-risk Screening MRI and Future Breast Cancer Risk.}, journal = {Academic radiology}, volume = {26}, number = {1}, pages = {69-75}, doi = {10.1016/j.acra.2018.03.013}, pmid = {29602724}, issn = {1878-4046}, mesh = {Adult ; Aged ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Cohort Studies ; Early Detection of Cancer ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; North Carolina/epidemiology ; Parenchymal Tissue/*diagnostic imaging ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {RATIONALE AND OBJECTIVES: To determine if background parenchymal enhancement (BPE) on screening breast magnetic resonance imaging (MRI) in high-risk women correlates with future cancer.

MATERIALS AND METHODS: All screening breast MRIs (n = 1039) in high-risk women at our institution from August 1, 2004, to July 30, 2013, were identified. Sixty-one patients who subsequently developed breast cancer were matched 1:2 by age and high-risk indication with patients who did not develop breast cancer (n = 122). Five fellowship-trained breast radiologists independently recorded the BPE. The median reader BPE for each case was calculated and compared between the cancer and control cohorts.

RESULTS: Cancer cohort patients were high-risk because of a history of radiation therapy (10%, 6 of 61), high-risk lesion (18%, 11 of 61), or breast cancer (30%, 18 of 61); BRCA mutation (18%, 11 of 61); or family history (25%, 15 of 61). Subsequent malignancies were invasive ductal carcinoma (64%, 39 of 61), ductal carcinoma in situ (30%, 18 of 61) and invasive lobular carcinoma (7%, 4of 61). BPE was significantly higher in the cancer cohort than in the control cohort (P = 0.01). Women with mild, moderate, or marked BPE were 2.5 times more likely to develop breast cancer than women with minimal BPE (odds ratio = 2.5, 95% confidence interval: 1.3-4.8, P = .005). There was fair interreader agreement (κ = 0.39).

CONCLUSIONS: High-risk women with greater than minimal BPE at screening MRI have increased risk of future breast cancer.}, } @article {pmid29599829, year = {2018}, author = {Guo, C and Fu, M and Dilimina, Y and Liu, S and Guo, L}, title = {microRNA-10b expression and its correlation with molecular subtypes of early invasive ductal carcinoma.}, journal = {Experimental and therapeutic medicine}, volume = {15}, number = {3}, pages = {2851-2859}, pmid = {29599829}, issn = {1792-0981}, abstract = {The present study aimed to determine whether the expression of microRNA (miR)-10b was correlated with the molecular subtypes of early invasive ductal carcinoma of the breast. In situ hybridization was used to detect the expression of miR-10b in 193 patients diagnosed with early invasive ductal carcinoma. Immunohistochemistry was performed to evaluate the expression of estrogen receptor (ER)-α, progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2). The positive expression rate of miR-10b in patients with early invasive ductal carcinoma with ER-α (+) or PR (+) was decreased compared with ER-α (-) or PR (-) patients (P<0.05). Furthermore, the positive expression rate of miR-10b in patients with Her-2 (-) was significantly increased compared with patients that were Her-2 (+) (P=0.031). The positive expression rate of miR-10b in the luminal B subtype was significantly decreased compared with that in the luminal A, Her-2 and basal-like subtypes (P=0.037). In patients that were identified as miR-10b (+), the median disease-free survival time was significantly increased in patients that were ER-α (+)/PR (+)/Her-2 (-) compared with patients that were ER-α (-)/PR (-)/Her-2 (+) (P<0.05). In addition, the median disease-free survival time was significantly decreased in Her-2 overexpression and basal-like subtypes when compared with luminal A and B subtypes (P<0.05). The molecular subtype was an independent prognostic factor for early invasive ductal carcinoma (odds ratios for luminal B, Basal-like, and Her-2 overexpression were 2.900, 5.232 and 4.214, respectively; all P<0.05). Positive expression of miR-10b may also be a prognostic risk factor (odds ratio >1), though this was not statistically significant (P>0.05). The present findings indicated that miR-10b-positive expression was correlated with the expression of ER-α, Her-2 and the molecular subtypes of early invasive ductal carcinoma of the breast.}, } @article {pmid29599319, year = {2018}, author = {Litwin, M and Szczepańska-Buda, A and Michałowska, D and Grzegrzółka, J and Piotrowska, A and Gomułkiewicz, A and Wojnar, A and Dzięgiel, P and Witkiewicz, W}, title = {Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {38}, number = {4}, pages = {2021-2030}, doi = {10.21873/anticanres.12441}, pmid = {29599319}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Argonaute Proteins/*biosynthesis/genetics ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; RNA, Messenger/biosynthesis/genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND/AIM: P-Element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) are involved in epigenetic regulation of gene expression in germline cells. Aberrant expression of piRNA and PIWI proteins have been identified in various types of tumour cells. The aim of this study was to evaluate the expression profiles of PIWI-like protein-1, -2 (PIWIL1 and PIWIL2), their immunohistochemical (IHC) characteristics in ductal breast cancer, and determine their correlation with clinicopathological parameters of this type of cancer.

MATERIALS AND METHODS: Material for IHC studies comprised of 101 invasive ductal carcinoma (IDC) cases and 31 mastopathy tissues. Frozen fragments of paired tissue specimens (tumour and adjacent non-malignant breast tissue) taken from 55 patients with IDC and 18 samples of mastopathy were used for molecular studies using real-time polymerase chain reaction (RT-PCR).

RESULTS: A statistically significantly higher level of PIWIL1 and PIWIL2 was found in IDC compared to mastopathy samples (p≤0.0001). Increased expression of PIWIL1 was correlated with increased PIWIL2 expression in breast cancer tissue. Surprisingly, PIWIL1 mRNA was detected only in cancer and mastopathy, but was not found in most normal breast tissues, although it is noteworthy that the PIWIL2 mRNA level was statistically significantly lower in mastopathy and IDC samples compared to normal breast tissues.

CONCLUSION: Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development.}, } @article {pmid29593583, year = {2018}, author = {Bar-Zomer, J and Brunstein Klomek, A}, title = {Attachment to Parents As a Moderator in the Association between Sibling Bullying and Depression or Suicidal Ideation among Children and Adolescents.}, journal = {Frontiers in psychiatry}, volume = {9}, number = {}, pages = {72}, pmid = {29593583}, issn = {1664-0640}, abstract = {Bullying is one of the most widespread phenomenon in childhood and adolescence. Interestingly, most research on bullying focuses on bullying at school and not on bullying among siblings at home. Sibling bullying is the most frequent form of repeated aggression that children experience in their lifetime. Furthermore, previous studies indicate that sibling bullying is associated with depression and self-harm behavior. However, the association between sibling bullying and suicidal ideation was never previously examined. Attachment to parents is one variable that can moderate the association between sibling bullying and depression/suicide ideation. To our knowledge, there is no existing study that examines the association between sibling bullying and attachment patterns. In addition, no previous study has examined the moderating role of attachment on the association between sibling bullying and depression or suicidal ideation among adolescents. The current study includes 279 Israeli students aged 10-17 (M = 13.5; SD = 1.98; 164, 58.8% females) who completed self-report questionnaires regarding school and sibling bullying, attachment to mother and father, depression, and suicidal ideation. The results indicated an association between bullying among siblings and school bullying. In addition, children and adolescents who were consistently involved in sibling bullying were at greater risk for depression and suicide ideation when compared to children and adolescents who were not involved in sibling bullying. A secure attachment to one's father (but not to one's mother) moderated the association between sibling bullying and depression/suicide ideation. It should be noted that when suicide ideation was examined above and beyond depression, attachment to one's father did not moderate the association between sibling bullying involvement and suicide ideation. This finding indicates that depression plays a central role in the association between sibling bullying and suicide ideation. These results suggest that sibling bullying is a risk factor for depressive symptoms and suicide ideation and that secure attachment to one's father may serve as a protective role. Future bullying prevention programs should include sibling bullying and encourage the increased availability of paternal emotional support. Other theoretical and applied implications for prevention of both sibling bullying and suicide are discussed.}, } @article {pmid29593431, year = {2018}, author = {Wu, SG and Zhang, WW and Sun, JY and He, ZY}, title = {Prognostic value of ductal carcinoma in situ component in invasive ductal carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis.}, journal = {Cancer management and research}, volume = {10}, number = {}, pages = {527-534}, pmid = {29593431}, issn = {1179-1322}, abstract = {BACKGROUND: The prognostic implication of concomitant ductal carcinoma in situ (DCIS) in invasive ductal carcinoma (IDC) remains controversial. Our objective was to investigate whether concomitant DCIS affects survival outcomes in patients with IDC.

MATERIALS AND METHODS: Patients with nonmetastatic breast cancer who underwent surgery in 2010-2014 were included from the Surveillance, Epidemiology, and End Results program. Statistical analyses were conducted using χ[2] test, linear-by-linear association, one-way analysis of variance, Kaplan-Meier method, Cox proportional hazards regression model, and propensity score matching (PSM).

RESULTS: A total of 61,745 patients were identified, including 44,630 (72.3%), 13,559 (22.0%), and 3,556 (5.7%) patients with no DCIS component reported (No-DCIS), DCIS <25% (L-DCIS), and ≥25% (H-DCIS), respectively. Patients with H-DCIS were more likely to be younger (p<0.001), have smaller tumors (p<0.001), good/moderate differentiation (p<0.001), human epidermal growth factor receptor 2-positive disease (p<0.001), receive mastectomy (p<0.001), and not receive radiotherapy (p<0.001) and chemotherapy (p<0.001). The median follow-up was 27 months, and the 2-year breast cancer-specific survival (BCSS) in patients with No-DCIS, L-DCIS, and H-DCIS was 97.3%, 98.0%, and 98.5%, respectively (p<0.001). Before PSM, H-DCIS was an independent favorable prognostic factor for BCSS; patients with H-DCIS had better BCSS compared to patients with No-DCIS (hazard ratio [HR] 0.674, 95% CI: 0.528-0.861, p=0.002), while the BCSS between No-DCIS and L-DCIS was similar (HR 0.944, 95% CI: 0.840-1.061, p=0.334). However, this survival advantage disappeared after PSM; there was significantly different BCSS between patients with No-DCIS and H-DCIS (HR 0.923, 95% CI: 0.653-1.304, p=0.650). H-DCIS was not associated with BCSS as compared to No-DCIS in the breast-conserving surgery (p=0.295) and mastectomy (p=0.793) groups.

CONCLUSION: In breast cancer, patients with H-DCIS have unique clinicopathologic features compared to patients with No-DCIS. Before PSM, H-DCIS was associated with favorable BCSS as compared to No-DCIS. However, the survival advantage disappeared after PSM.}, } @article {pmid29587169, year = {2019}, author = {Szepsenwol, O and Simpson, JA}, title = {Attachment within life history theory: an evolutionary perspective on individual differences in attachment.}, journal = {Current opinion in psychology}, volume = {25}, number = {}, pages = {65-70}, doi = {10.1016/j.copsyc.2018.03.005}, pmid = {29587169}, issn = {2352-2518}, mesh = {Adaptation, Psychological ; Anxiety/*psychology ; Emotional Regulation ; Female ; Humans ; Interpersonal Relations ; *Life History Traits ; Male ; *Object Attachment ; Psychological Theory ; }, abstract = {In this article, we discuss theory and research on how individual differences in adult attachment mediate the adaptive calibration of reproductive strategies, cognitive schemas, and emotional expression and regulation. We first present an integration of attachment theory and life history theory. Then, we discuss how early harsh and/or unpredictable environments may promote insecure attachment by hampering parents' ability to provide sensitive and reliable care to their children. Finally, we discuss how, in the context of harsh and/or unpredictable environments, different types of insecure attachment (i.e. anxiety and avoidance) may promote evolutionary adaptive reproductive strategies, cognitive schemas, and emotional expression and regulation profiles.}, } @article {pmid29581709, year = {2018}, author = {Monti, S and Aiello, M and Incoronato, M and Grimaldi, AM and Moscarino, M and Mirabelli, P and Ferbo, U and Cavaliere, C and Salvatore, M}, title = {DCE-MRI Pharmacokinetic-Based Phenotyping of Invasive Ductal Carcinoma: A Radiomic Study for Prediction of Histological Outcomes.}, journal = {Contrast media & molecular imaging}, volume = {2018}, number = {}, pages = {5076269}, pmid = {29581709}, issn = {1555-4317}, mesh = {Adult ; Aged ; Area Under Curve ; Breast Neoplasms/*classification/diagnostic imaging ; Carcinoma, Ductal/*classification/diagnostic imaging ; Contrast Media ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Magnetic Resonance Imaging/*methods ; Middle Aged ; *Models, Theoretical ; Neoplasm Grading ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Triple Negative Breast Neoplasms ; Young Adult ; }, abstract = {Breast cancer is a disease affecting an increasing number of women worldwide. Several efforts have been made in the last years to identify imaging biomarker and to develop noninvasive diagnostic tools for breast tumor characterization and monitoring, which could help in patients' stratification, outcome prediction, and treatment personalization. In particular, radiomic approaches have paved the way to the study of the cancer imaging phenotypes. In this work, a group of 49 patients with diagnosis of invasive ductal carcinoma was studied. The purpose of this study was to select radiomic features extracted from a DCE-MRI pharmacokinetic protocol, including quantitative maps of k[trans], kep, ve, iAUC, and R1 and to construct predictive models for the discrimination of molecular receptor status (ER+/ER-, PR+/PR-, and HER2+/HER2-), triple negative (TN)/non-triple negative (NTN), ki67 levels, and tumor grade. A total of 163 features were obtained and, after feature set reduction step, followed by feature selection and prediction performance estimations, the predictive model coefficients were computed for each classification task. The AUC values obtained were 0.826 ± 0.006 for ER+/ER-, 0.875 ± 0.009 for PR+/PR-, 0.838 ± 0.006 for HER2+/HER2-, 0.876 ± 0.007 for TN/NTN, 0.811 ± 0.005 for ki67+/ki67-, and 0.895 ± 0.006 for lowGrade/highGrade. In conclusion, DCE-MRI pharmacokinetic-based phenotyping shows promising for discrimination of the histological outcomes.}, } @article {pmid29580241, year = {2018}, author = {Majumder, A and Syed, KM and Mukherjee, A and Lankadasari, MB and Azeez, JM and Sreeja, S and Harikumar, KB and Pillai, MR and Dutta, D}, title = {Enhanced expression of histone chaperone APLF associate with breast cancer.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {76}, pmid = {29580241}, issn = {1476-4598}, mesh = {Animals ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; DNA-(Apurinic or Apyrimidinic Site) Lyase/*metabolism ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Transplantation ; Poly-ADP-Ribose Binding Proteins/*metabolism ; Tissue Array Analysis ; Triple Negative Breast Neoplasms/metabolism/pathology ; *Up-Regulation ; }, abstract = {DNA damage-specific histone chaperone Aprataxin PNK-like factor (APLF) regulates mesenchymal-to-epithelial transition (MET) during cellular reprogramming. We investigated the role of APLF in epithelial-to-mesenchymal transition (EMT) linked to breast cancer invasiveness and metastasis. Here, we show that a significant manifestation of APLF is present in tumor sections of patients with invasive ductal carcinoma when compared to their normal adjacent tissues. APLF was significantly induced in triple negative breast cancer (TNBC) cells, MDAMB-231, in comparison to invasive MCF7 or normal MCF10A breast cells and supported by studies on invasive breast carcinoma in The Cancer Genome Atlas (TCGA). Functionally, APLF downregulation inhibited proliferative capacity, altered cell cycle behavior, induced apoptosis and impaired DNA repair ability of MDAMB-231 cells. Reduction in APLF level impeded invasive, migratory, tumorigenic and metastatic potential of TNBC cells with loss in expression of genes associated with EMT while upregulation of MET-specific gene E-cadherin (CDH1). So, here we provided novel evidence for enrichment of APLF in breast tumors, which could regulate metastasis-associated EMT in invasive breast cancer. We anticipate that APLF could be exploited as a biomarker for breast tumors and additionally could be targeted in sensitizing cancer cells towards DNA damaging agents.}, } @article {pmid29579338, year = {2018}, author = {Uemura, MI and French, JT and Hess, KR and Liu, D and Raghav, K and Hortobagyi, GN and Arun, BK and Valero, V and Ueno, NT and Alvarez, RH and Woodward, WA and Debeb, BG and Moulder, SL and Lim, B and Tripathy, D and Ibrahim, NK}, title = {Development of CNS metastases and survival in patients with inflammatory breast cancer.}, journal = {Cancer}, volume = {124}, number = {11}, pages = {2299-2305}, doi = {10.1002/cncr.31336}, pmid = {29579338}, issn = {1097-0142}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Breast/pathology/surgery ; Central Nervous System Neoplasms/*epidemiology/prevention & control/secondary ; Chemotherapy, Adjuvant/methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Inflammatory Breast Neoplasms/mortality/*pathology/therapy ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Taxoids/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Inflammatory breast cancer (IBC) is associated with a poor prognosis and high risk of central nervous system (CNS) metastases.

METHODS: We retrospectively reviewed stage III-IBC patients compared with noninflammatory invasive ductal carcinoma (NI-IDC) patients treated between January 1, 1984, and December 31, 2011, who began primary treatment within 1 year of diagnosis and had been followed up for at least 1 year before the development of CNS metastasis or death. Cumulative CNS metastasis incidence and post-CNS metastasis overall survival (OS) estimates were computed. Multivariable Cox proportional hazard models explored factors for post-CNS metastasis survival.

RESULTS: A total of 2323 patients were identified (589-IBC/1734-NI-IDC). Eighty-one IBC patients developed CNS metastasis, versus 154 NI-IDC patients. The 2-, 5-, and 10-year cumulative CNS metastasis incidence rates in IBC and NI-IDC were 9.8%, 15.8%, 17.4% and 6.5%, 10.1%, and 12.7%, respectively. This was significantly different between IBC and NI-IDC patients (P = .0037). Multicovariate competing risk regression models in IBC and NI-IDC patients showed no statistically significant associations with the risk of developing CNS metastasis, except neoadjuvant taxane use in NI-IDC patients (hazard ratio, 0.45; 95% confidence interval, 0.24-0.83; P = .011). The median follow-up was 7.2 years, and the median post-CNS metastasis OS was not significantly different between IBC (7.6 months) and NI-IDC (5.6 months) patients. One hundred ninety patients with CNS metastasis died. HER2-positive patients had better OS, with a median 14.1 versus 4.3 months (P < .0001). Age >50 years (P = .012) but not IBC status was a significant predictor of post-CNS metastasis survival.

CONCLUSION: IBC patients demonstrated higher CNS metastasis incidence rates but OS following CNS metastases is similar in both groups. HER2 status and age may play prognostic roles. Cancer 2018;124:2299-305. © 2018 American Cancer Society.}, } @article {pmid29578737, year = {2018}, author = {Morvinski, C and Amir, O}, title = {Liking goes with liking: An intuitive congruence between preference and prominence.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {44}, number = {6}, pages = {944-961}, doi = {10.1037/xlm0000471}, pmid = {29578737}, issn = {1939-1285}, mesh = {Adult ; *Choice Behavior ; Cues ; Emotions ; Female ; Humans ; Male ; Psychological Theory ; Young Adult ; }, abstract = {In a series of 8 experiments, we demonstrate the existence of a "labeling effect" wherein people intuitively relate preferred choices to prominently labeled cues (such as heads as opposed to tails in a coin toss) and vice versa. Importantly, the observed congruence is asymmetric-it does not manifest for nonprominent cues and nonpreferred choices. This is because the congruence is driven by a process of evaluative matching: prominent cues are liked, but nonprominent cues are neutral or at most slightly negative in contrast. When we test prominent, yet truly negatively labeled cues, we indeed find a matching with less liked products. We discuss the theoretical contributions to the study of preferences and decision making, as well as demonstrate the practical implications to researchers and practitioners by using this process to assess intuitive preferences and reduce the compromise effect. (PsycINFO Database Record}, } @article {pmid29575844, year = {2018}, author = {Yao, C and Chen, LL and Li, YP and Peng, CZ and Li, MK and Yao, J}, title = {[Multi-variated analysis of differential diagnosis in ultrasonography of idiopathic granulomatous mastitis and invasive ductal carcinoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {40}, number = {3}, pages = {222-226}, doi = {10.3760/cma.j.issn.0253-3766.2018.03.013}, pmid = {29575844}, issn = {0253-3766}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Granulomatous Mastitis/*diagnostic imaging/pathology ; Hemodynamics ; Humans ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; Ultrasonography, Doppler, Color ; Ultrasonography, Mammary ; }, abstract = {Objective: To evaluate the differential diagnosis of idiopathic granulomatous mastitis (IGM) and invasive ductal carcinoma. Methods: The ultrasonographic data of 37 IGM patients and 50 cases of IDC were analyzed retrospectively. The shape, growth direction, margin, internal echo, posterior echo, calcification, Adler blood flow classification, PSV(peak sestolic velocity), RI (resistance index)and elasticity scores were analyzed by χ(2) test and independent sample t test. The optimal cutoff values of age, PSV and RI were calculated by receiver operating characteristic (ROC) curve. Logistic regression analysis was used to calculate the odds ratio (OR) of ultrasonic variates in the diagnosis of both diseases. Results: There were no significant differences in the shape, margin, internal echo and blood flow grading between the two groups. The age, lesion growth direction, posterior echo, calcification, PSV, RI and elasticity were statistically different. The cut-of value of Age, PSV and RI were 38.5 years old, 13.20 cm/s, and 0.655. Logistic regression multi-variated analysis revealed that elastic score (OR=9.806) had the best value of the differential diagnosis, as well as calcification (OR=6.937), posterior echo decay (OR=4.613), RI (OR=3.257), lesion growth orientation (OR=3.198), and PSV (OR=1.202). Lesion shape, margin, internal echo, and Adler blood flow classification did not help in differential diagnosis. Conclusion: Ultrasound multi-parameter analysis has high value in IGM and IDC differential diagnosis.}, } @article {pmid29574881, year = {2018}, author = {Nakaguro, M and Urano, M and Suzuki, H and Yamada, K and Sakaguchi, A and Ogura, K and Matsumoto, T and Ono, N and Asato, T and Mikami, Y and Imai, H and Nagao, T}, title = {Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant.}, journal = {Histopathology}, volume = {73}, number = {2}, pages = {314-320}, doi = {10.1111/his.13517}, pmid = {29574881}, issn = {1365-2559}, mesh = {Aged ; Carcinoma, Ductal/*pathology ; Female ; Humans ; Male ; Middle Aged ; Oxyphil Cells/pathology ; Salivary Gland Neoplasms/*pathology ; }, abstract = {AIMS: Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands.

METHODS AND RESULTS: We examined five cases, three males and two females (mean age = 63 years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour.

CONCLUSION: Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.}, } @article {pmid29569445, year = {2018}, author = {Putin, E and Asadulaev, A and Vanhaelen, Q and Ivanenkov, Y and Aladinskaya, AV and Aliper, A and Zhavoronkov, A}, title = {Adversarial Threshold Neural Computer for Molecular de Novo Design.}, journal = {Molecular pharmaceutics}, volume = {15}, number = {10}, pages = {4386-4397}, doi = {10.1021/acs.molpharmaceut.7b01137}, pmid = {29569445}, issn = {1543-8392}, mesh = {*Machine Learning ; *Neural Networks, Computer ; }, abstract = {In this article, we propose the deep neural network Adversarial Threshold Neural Computer (ATNC). The ATNC model is intended for the de novo design of novel small-molecule organic structures. The model is based on generative adversarial network architecture and reinforcement learning. ATNC uses a Differentiable Neural Computer as a generator and has a new specific block, called adversarial threshold (AT). AT acts as a filter between the agent (generator) and the environment (discriminator + objective reward functions). Furthermore, to generate more diverse molecules we introduce a new objective reward function named Internal Diversity Clustering (IDC). In this work, ATNC is tested and compared with the ORGANIC model. Both models were trained on the SMILES string representation of the molecules, using four objective functions (internal similarity, Muegge druglikeness filter, presence or absence of sp[3]-rich fragments, and IDC). The SMILES representations of 15K druglike molecules from the ChemDiv collection were used as a training data set. For the different functions, ATNC outperforms ORGANIC. Combined with the IDC, ATNC generates 72% of valid and 77% of unique SMILES strings, while ORGANIC generates only 7% of valid and 86% of unique SMILES strings. For each set of molecules generated by ATNC and ORGANIC, we analyzed distributions of four molecular descriptors (number of atoms, molecular weight, logP, and tpsa) and calculated five chemical statistical features (internal diversity, number of unique heterocycles, number of clusters, number of singletons, and number of compounds that have not been passed through medicinal chemistry filters). Analysis of key molecular descriptors and chemical statistical features demonstrated that the molecules generated by ATNC elicited better druglikeness properties. We also performed in vitro validation of the molecules generated by ATNC; results indicated that ATNC is an effective method for producing hit compounds.}, } @article {pmid29568948, year = {2018}, author = {Ren, W and Zhang, Y and Zhang, L and Lin, Q and Zhang, J and Xu, G}, title = {Overexpression of collagen type V α1 chain in human breast invasive ductal carcinoma is mediated by TGF-β1.}, journal = {International journal of oncology}, volume = {52}, number = {5}, pages = {1694-1704}, doi = {10.3892/ijo.2018.4317}, pmid = {29568948}, issn = {1791-2423}, abstract = {Collagen type V α1 chain (COL5A1) is a minor fibrillar collagen in mammals that co-polymerizes with type I collagen to adjust the diameter of collagen molecules. However, the function of COL5A1 in invasive ductal carcinoma (IDC) of the human breast remains unknown. In the present study, our group examined the expression of COL5A1 in IDC compared with its adjacent normal tissue and fibroadenoma of the breast. COL5A1 was revealed to be overexpressed in IDC compared with benign tumor and adjacent normal control tissues, and was associated with the expression of estrogen receptor and progesterone receptor. No association between COL5A1 expression and tumor size, lymph node metastasis, clinical stage, age, or Her2 expression was identified. High expression of COL5A1 mRNA was associated with distant metastasis free survival in patients with breast cancer. Knockdown of COL5A1 led to a decrease of cell viability, as detected by the WST-1 assay, and an inhibition of migration and invasion, as detected by wound healing and Transwell assays, respectively, in the breast cancer cell line MCF-7. The expression of COL5A1 in MCF-7 cells was downregulated by transforming growth factor (TGF)‑β1, which was abolished in the presence of SB-431542, an inhibitor of TGF-β type I receptor. In conclusion, these data indicated that COL5A1 is overexpressed in IDC and regulated by TGF-β1, suggesting that an increase of COL5A1 reflects tumor progression and may serve as a novel biomarker and therapeutic target for the treatment of breast IDC.}, } @article {pmid29556054, year = {2018}, author = {Veeraraghavan, H and Dashevsky, BZ and Onishi, N and Sadinski, M and Morris, E and Deasy, JO and Sutton, EJ}, title = {Appearance Constrained Semi-Automatic Segmentation from DCE-MRI is Reproducible and Feasible for Breast Cancer Radiomics: A Feasibility Study.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {4838}, pmid = {29556054}, issn = {2045-2322}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Automation ; Breast Neoplasms/*diagnostic imaging ; Feasibility Studies ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; *Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {We present a segmentation approach that combines GrowCut (GC) with cancer-specific multi-parametric Gaussian Mixture Model (GCGMM) to produce accurate and reproducible segmentations. We evaluated GCGMM using a retrospectively collected 75 invasive ductal carcinoma with ERPR+ HER2- (n = 15), triple negative (TN) (n = 9), and ER-HER2+ (n = 57) cancers with variable presentation (mass and non-mass enhancement) and background parenchymal enhancement (mild and marked). Expert delineated manual contours were used to assess the segmentation performance using Dice coefficient (DSC), mean surface distance (mSD), Hausdorff distance, and volume ratio (VR). GCGMM segmentations were significantly more accurate than GrowCut (GC) and fuzzy c-means clustering (FCM). GCGMM's segmentations and the texture features computed from those segmentations were the most reproducible compared with manual delineations and other analyzed segmentation methods. Finally, random forest (RF) classifier trained with leave-one-out cross-validation using features extracted from GCGMM segmentation resulted in the best accuracy for ER-HER2+ vs. ERPR+/TN (GCGMM 0.95, expert 0.95, GC 0.90, FCM 0.92) and for ERPR + HER2- vs. TN (GCGMM 0.92, expert 0.91, GC 0.77, FCM 0.83).}, } @article {pmid29554537, year = {2018}, author = {Fukai, S and Yoshida, A and Akiyama, F and Tsunoda, H and Lefor, AK and Kimura, J and Sakamoto, T and Suzuki, K and Mizokami, K}, title = {Ductal Carcinoma in situ of the breast in sclerosing adenosis encapsulated by a hamartoma: A case report.}, journal = {International journal of surgery case reports}, volume = {45}, number = {}, pages = {9-12}, pmid = {29554537}, issn = {2210-2612}, abstract = {INTRODUCTION: Ductal Carcinoma in situ (DCIS) of the breast can develop in areas of sclerosing adenosis. The radiographic finding of sclerosing adenosis is a spiculated mass and can look like invasive ductal carcinoma. We report a patient with DCIS in sclerosing adenosis encapsulated by a hamartoma, with imaging findings quite different from the typical findings of sclerosing adenosis.

PRESENTATION OF CASE: A 73-year old woman, with no previous mammography, presented with a palpable mass in the left breast. Mammography showed a 36 mm well-defined mass with fat density in the middle outer quadrant of the left breast. Ultrasonography showed a well-defined mass in the same area which was composed of hypoechoic and hyperechoic areas. The histological diagnosis by core needle biopsy was sclerosing adenosis. We considered the patient's age and tumor size and performed a partial mastectomy for both diagnosis and treatment. Final pathology showed DCIS in sclerosing adenosis in a hamartoma.

DISCUSSION: This patient had DCIS in an area of sclerosing adenosis, encapsulated by a hamartoma. DCIS can develop in areas of sclerosing adenosis, and can appear similar to invasive ductal carcinoma, so we must avoid misdiagnosis or over-treatment. Malignant transformation of a hamartoma is rare, but can occur since it contains epithelial tissue. Definitive biopsy should be performed due to the possibility of a malignancy inside the hamartoma.

CONCLUSIONS: When diagnosing a hamartoma, the presence of atypical findings on imaging studies, should suggest the possibility of malignancy. Although rare, a malignant tumor may be present inside the hamartoma.}, } @article {pmid29551677, year = {2018}, author = {Luo, J and Feng, J and Wen, Q and Qoyawayma, C and Wang, W and Chen, L and Lu, J and Zhan, Y and Xu, L and Zang, H and Fan, S and Chu, S}, title = {Elevated expression of IRS-1 associates with phosphorylated Akt expression and predicts poor prognosis of breast invasive ductal carcinoma.}, journal = {Human pathology}, volume = {79}, number = {}, pages = {9-17}, doi = {10.1016/j.humpath.2018.03.003}, pmid = {29551677}, issn = {1532-8392}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*enzymology/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*enzymology/mortality/pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Insulin Receptor Substrate Proteins/*analysis ; Middle Aged ; Neoplasm Invasiveness ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/*analysis ; Risk Factors ; Time Factors ; Tissue Array Analysis ; Up-Regulation ; }, abstract = {Overexpression of insulin receptor substrate 1 (IRS-1) has been reported to promote cell growth, atypical hyperplasia, and carcinogenesis, and phosphorylated Akt (p-Akt) is certified to be involved in many types of cancers such as breast invasive ductal carcinoma (BIDC). However, the relationship between IRS-1 and Akt, as well as the role of expression of IRS-1 in BIDC, has never been reported. The purpose of this research is to investigate the association between expression of IRS-1 and p-Akt proteins and clinicopathological features of BIDC by immunohistochemistry, as well as the survival status. The results showed that the percentage of either elevated expression of IRS-1 or positive p-Akt expression in BIDC was significantly higher than that in control breast tissue from noncancer patients (P < .001 and P = .001, respectively). Overexpression of IRS-1 was evidently associated with positive expression of p-Akt (r = 0.337, P < .001). Also, positive percentage of p-Akt expression was statistically different among different molecular subtypes of BIDC (highest in luminal B BIDC, P = .009). Furthermore, significantly worse overall survival was found in BIDC patients with high expression of IRS-1 and p-Akt than in patients with low expression (P = .006 and P = .004, respectively). The multivariate Cox proportional hazard regression analysis showed that high expression of IRS-1 and positive expression of p-Akt protein were independent poor prognostic factors for patients with BIDC (P = .022 and P = .046, respectively). In conclusion, we report for the first time that overexpression of IRS-1 protein is associated with expression of p-Akt, and overexpression of IRS-1 and positive expression of p-Akt might be independent biomarkers for poor prognosis in BIDC.}, } @article {pmid29551588, year = {2018}, author = {Moraru, A and Wiederstein, J and Pfaff, D and Fleming, T and Miller, AK and Nawroth, P and Teleman, AA}, title = {Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.}, journal = {Cell metabolism}, volume = {27}, number = {4}, pages = {926-934.e8}, doi = {10.1016/j.cmet.2018.02.003}, pmid = {29551588}, issn = {1932-7420}, mesh = {Animals ; Cells, Cultured ; Diabetes Mellitus, Type 2/*metabolism ; Drosophila melanogaster ; Hyperglycemia/metabolism ; Insulin Resistance ; Lactoylglutathione Lyase/genetics ; Obesity/metabolism ; Pyruvaldehyde/*metabolism ; }, abstract = {The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.}, } @article {pmid29546871, year = {2018}, author = {Steardo, L}, title = {[The IDC-11 Chapter on Mental Disorders Is Going to Be Finalized].}, journal = {Psychiatria Danubina}, volume = {30}, number = {1}, pages = {114-117}, pmid = {29546871}, issn = {0353-5053}, } @article {pmid29546577, year = {2018}, author = {Mendler, M and Kopf, S and Groener, JB and Riedinger, C and Fleming, TH and Nawroth, PP and Okun, JG}, title = {Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes.}, journal = {Acta diabetologica}, volume = {55}, number = {6}, pages = {585-592}, doi = {10.1007/s00592-018-1130-2}, pmid = {29546577}, issn = {1432-5233}, support = {CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; CRC1118//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adenylate Kinase/metabolism ; Adult ; Aged ; Aminoimidazole Carboxamide/*analogs & derivatives/urine ; Animals ; Case-Control Studies ; Cohort Studies ; Diabetes Complications/metabolism/prevention & control/urine ; Diabetes Mellitus, Type 2/complications/metabolism/prevention & control/*urine ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State/pathology/therapy/urine ; Ribonucleotides/*urine ; Risk Factors ; Risk Reduction Behavior ; Signal Transduction/physiology ; }, abstract = {AIMS: 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an endogenous activator of AMPK, a central regulator of energy homeostasis. Loss and/or reduction of AMPK signaling plays an important role in the development of insulin resistance in type 2 diabetes. The loss of AMPK in diabetes could be due to a loss of AICAR. The aim of this study was to characterize urine levels of AICAR in diabetes and determine whether an association exists with respect to late complications, e.g., retinopathy, nephropathy and neuropathy.

METHODS: Urine AICAR was measured by liquid chromatography tandem mass spectrometry in 223 patients consisting of 5 healthy controls, 63 patients with pre-diabetes, 29 patients with newly diagnosed type 2 diabetes and 126 patients with long-standing type 2 diabetes. For statistical analyses, nonparametric Kruskal-Wallis test, one-way ANOVA and multivariate regression analysis were performed to investigate the associations of urinary AICAR excretion within different groups and different clinical parameters.

RESULTS: The mean urine AICAR for all 223 patients was 694.7 ± 641.1 ng/ml. There was no significant difference in urine AICAR between the control and patients with diabetes (592.3 ± 345.1 vs. 697.1 ± 646.5 ng/ml). No association between any of the biochemical and/or clinical parameters measured and urine AICAR was found, with the exception of age of patient (R = - 0.34; p < 0.01) and estimated glomerular filtration rate (R = 0.19; p = 0.039). These results were confirmed additionally by linear regression analysis.

CONCLUSIONS: Clinical diabetes is not associated with a change in endogenous AICAR levels. Loss of AICAR may therefore not be a mechanism by which AMPK signaling is reduced in diabetes.}, } @article {pmid29538201, year = {2018}, author = {Hsu, CC and Li, WY and Chu, PY}, title = {Salivary duct carcinoma of the supraglottis with a distinct presentation: A case report and literature review.}, journal = {Medicine}, volume = {97}, number = {11}, pages = {e0095}, pmid = {29538201}, issn = {1536-5964}, mesh = {Airway Obstruction/etiology/surgery ; *Carcinoma/pathology/physiopathology/therapy ; Chemoradiotherapy/*methods ; *Cytoreduction Surgical Procedures/instrumentation/methods ; Humans ; *Larynx/pathology/physiopathology/surgery ; Lasers, Gas/therapeutic use ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Salivary Ducts/*pathology ; *Salivary Gland Neoplasms/pathology/physiopathology/therapy ; Salivary Glands, Minor/*pathology ; Treatment Outcome ; }, abstract = {RATIONALE: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC.

PATIENT CONCERNS: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months.

DIAGNOSES: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx.

INTERVENTIONS: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged.

OUTCOMES: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis.

LESSONS: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.}, } @article {pmid29538032, year = {2018}, author = {Kumar, R and Mittal, BR and Bhattacharya, A and Singh, H and Singh, SK}, title = {Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {6}, pages = {431-432}, doi = {10.1097/RLU.0000000000002063}, pmid = {29538032}, issn = {1536-0229}, mesh = {Breast Neoplasms, Male/*diagnostic imaging ; Carcinoma/*diagnostic imaging ; Edetic Acid/analogs & derivatives ; Gallium Isotopes ; Gallium Radioisotopes ; Humans ; Male ; Middle Aged ; Oligopeptides ; *Positron Emission Tomography Computed Tomography ; Prostatic Neoplasms/*diagnostic imaging ; Radiopharmaceuticals ; }, abstract = {The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.}, } @article {pmid31298999, year = {2018}, author = {Soldevilla-Gallardo, I and Villaseñor-Navarro, Y and Medina-Ornelas, SS and Villarreal-Garza, C and Bargalló-Rocha, E and Caro-Sánchez, CH and Gallardo-Alvarado, LN and Hernández-Ramírez, R and Arela-Quispe, LM and García-Pérez, FO}, title = {Positron emission mammography in the evaluation of interim response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.}, journal = {Cancer treatment and research communications}, volume = {16}, number = {}, pages = {24-31}, doi = {10.1016/j.ctarc.2018.05.001}, pmid = {31298999}, issn = {2468-2942}, abstract = {UNLABELLED: Neoadjuvant chemotherapy (NAC) has an important role in patients with locally advanced cancers, treating distant micrometastases, downstaging tumors, improving operability, and sometimes allowing breast-conserving surgery to take place. We studied the association between two Positron Emission Mammography with [18]F-FDG ([18]F-FDG-PEM) semi-quantitative parameters in 108 patients and correlated with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers.

AIM: Examine the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of NAC with pathologic response in each breast cancer subtype.

METHODS: 108 patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with [18]F-FDG-PEM scans baseline and after end of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG).

RESULTS: After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ± 0.26 vs. 1.9 ± 0.18; p < 0.001) and LTB exhibited a significant decay after the first course of NACT (15.8 ± 1.36 vs. 5.5 ± 0.49; p < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (p = 0.52), but if a correlation was found between the response rate by MPG and both semiquantitative parameters (p = 0.05).

CONCLUSION: 2 PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.}, } @article {pmid31007533, year = {2018}, author = {Takahashi, Y and Sato, M and Imai, M and Lorenz, R and Yair, Y and Aplin, K and Fischer, G and Nakamura, M and Ishii, N and Abe, T and Satoh, T and Imamura, T and Hirose, C and Suzuki, M and Hashimoto, GL and Hirata, N and Yamazaki, A and Sato, TM and Yamada, M and Murakami, SY and Yamamoto, Y and Fukuhara, T and Ogohara, K and Ando, H and Sugiyama, KI and Kashimura, H and Ohtsuki, S}, title = {Initiation of a lightning search using the lightning and airglow camera onboard the Venus orbiter Akatsuki.}, journal = {Earth, planets, and space : EPS}, volume = {70}, number = {1}, pages = {88}, pmid = {31007533}, issn = {1343-8832}, abstract = {The existence of lightning discharges in the Venus atmosphere has been controversial for more than 30 years, with many positive and negative reports published. The lightning and airglow camera (LAC) onboard the Venus orbiter, Akatsuki, was designed to observe the light curve of possible flashes at a sufficiently high sampling rate to discriminate lightning from other sources and can thereby perform a more definitive search for optical emissions. Akatsuki arrived at Venus during December 2016, 5 years following its launch. The initial operations of LAC through November 2016 have included a progressive increase in the high voltage applied to the avalanche photodiode detector. LAC began lightning survey observations in December 2016. It was confirmed that the operational high voltage was achieved and that the triggering system functions correctly. LAC lightning search observations are planned to continue for several years.}, } @article {pmid32300401, year = {2017}, author = {Shieh, A and Mohamed, AA}, title = {A Case of Therapy-Related Acute Myeloid Leukemia in a Patient With Heterozygous Mutations in the Ataxia Telangiectasia Mutated Gene.}, journal = {Journal of hematology}, volume = {6}, number = {4}, pages = {96-100}, pmid = {32300401}, issn = {1927-1212}, abstract = {Use of adjuvant chemotherapy has improved survival for many patients with breast cancer. Unfortunately, such treatment can come at a price, in particular, malignancies. We present a case of a 36-year-old woman with heterozygous mutations in the ataxia telangiectasia mutated (ATM) gene who was admitted to the hospital for fatigue and diffusely scattered bruises. She was diagnosed with invasive ductal carcinoma of the left breast and had bilateral mastectomy with axillary node clearance followed by adjuvant chemotherapy 3 years prior. Her vitals were stable. Lab tests revealed thrombocytopenia, leukocytosis, and anemia. Peripheral blood smear and bone marrow biopsy revealed numerous myeloblasts. After flow cytometry and FISH analysis were performed, a diagnosis of therapy-related acute myeloid leukemia (t-AML) was made. The patient was treated with induction chemotherapy and a bone marrow biopsy revealed residual disease. Re-induction therapy was given and a bone marrow biopsy revealed complete remission. She subsequently received an allogenic stem cell transplant and was cured. Her treatment course was uncomplicated. We raise the question as to whether certain chemotherapy agents should be avoided in patients with mutations in DNA repair genes. Furthermore, it is essential for physicians to educate patients on the risk of secondary malignancies arising from chemotherapeutic treatment.}, } @article {pmid31966881, year = {2017}, author = {Mo, CH and Ackbarkhan, Z and Gu, YY and Chen, G and Pang, YY and Dang, YW and Feng, ZB}, title = {Invasive cribriform carcinoma of the breast: a clinicopathological analysis of 12 cases with review of literature.}, journal = {International journal of clinical and experimental pathology}, volume = {10}, number = {9}, pages = {9917-9924}, pmid = {31966881}, issn = {1936-2625}, abstract = {Invasive cribriform carcinoma (ICC) is a rare type of invasive breast cancer. We aim to investigate the clinicopathological features, immunophenotypes, diagnosis and differential diagnosis of ICC. Thus, clinicopathological data of 12 ICC patients were collected. All 12 cases were female, aged 38 to 75 years, with a median age of 53 years old. The maximum diameter of the tumor was 2 cm to 10 cm, in which the median tumor size was 2.54 cm in pure ICC and classical ICC. Microscopically, the cancer nests of ICC assumed an invasive, irregular island-shaped distribution, with an irregular mesh structure internally and fibrous reactions around most cancer nests. 67% (8/12) of cases were grade 1 and 33% (4/12) of cases were grade 2 tumors. Immunohistochemically, ER and PR were moderately to strongly positive with the positive tumor cell number accounting for 30% to 95% in all cases. HER-2 was negative in all cases except in one case which was positive (2+). Myoepithelial markers such as Calponin, p63, CK5/6 and CD10 were all negative in the cancer nests. 58% (7/12) of cases had a ki67 index of ≤ 14%. All follow-up patients were followed for 12 to 70 months (with a mean of 42 months), and were disease-free after treatment except for one patient whom we lost during the follow up. In conclusion, ICC, as a special type of breast cancer, has its unique clinicopathological and immunophenotypic characteristics, leading to a good prognosis.}, } @article {pmid29900024, year = {2017}, author = {Porter, K and Rosenzweig, MQ}, title = {Current and Emerging Therapies for HER2-Positive Women With Metastatic Breast Cancer.}, journal = {Journal of the advanced practitioner in oncology}, volume = {8}, number = {2}, pages = {164-168}, pmid = {29900024}, issn = {2150-0878}, abstract = {CASE STUDY DE, a 31-year-old premenopausal woman with a nonsignificant medical history, noticed a right breast mass after playing basketball in September 2011. She initially attributed the mass to slight trauma, but after 2 weeks, she realized the mass was increasing in size. Her primary care physician ordered a bilateral screening mammogram and ultrasound. Mammography revealed no evidence of malignancy in the left breast. In the right breast, at the 7 o'clock position, a loose cluster of faint calcifications spanned a 2.2-cm area. Ultrasound confirmed an irregular hypoechoic mass in the right breast measuring 3.5 × 2.7 × 2.8 cm. Ultrasound of the right axilla identified two enlarged right axillary lymph nodes. Ultrasound core-needle biopsy of the suspicious right breast mass confirmed invasive ductal carcinoma, nuclear grade 2, Ki67 index of 55%, estrogen receptor-positive (H score of 180), progesterone receptor-positive (H score of 135), HER2-positive (3+ on immunohistochemistry). Utilizing the TNM (tumor, node, metastasis) staging system, she was clinically staged with a stage IIB (cT2, cN1, M0) invasive breast tumor. The computerized axial tomography (CT) scan of the chest, abdomen, and pelvis demonstrated the known right breast mass and two enlarged right axillary lymph nodes; however, no metastatic disease was noted. Nuclear bone scan revealed no bone metastases. Her medical oncologist recommended she receive neoadjuvant chemotherapy. The patient was treated with 6 cycles of neoadjuvant docetaxel at 75 mg/m[2], carboplatin at an AUC (area under the curve) of 6, and trastuzumab (Herceptin) at 6 mg/kg (TCH), which she tolerated well. She then underwent a right segmental mastectomy with axillary lymph node dissection and was found to have a residual 1.0-cm invasive ductal carcinoma, representing a 60% tumor volume reduction. None of 13 axillary lymph nodes were positive for disease. Pathologic staging confirmed a stage IA (ypT1, ypN0, M0) tumor. DE completed 33 fractions of radiation therapy to the right breast. She initiated endocrine therapy with tamoxifen at 20 mg daily and received 1 year of maintenance trastuzumab (6 mg/kg). Due to vaginal discharge and weight gain, endocrine therapy was switched from tamoxifen to toremifene (Fareston), which she tolerated relatively well. She continued routine follow-up, with no evidence of disease. In September 2014, DE presented to her primary care physician complaining of left hip pain. Magnetic resonance imaging (MRI) of the left hip revealed T2 hyperintense masses within the right anterior superior iliac crest, right sacrum, and left iliac body consistent with skeletal metastases. She was referred back to her medical oncologist, and per National Comprehensive Cancer Network (NCCN) guidelines, a biopsy of the suspicious lesion was obtained. The bone biopsy of the lytic lesion was consistent with metastatic breast cancer, which was estrogen receptor-positive, progesterone receptor-positive, and HER2-positive (3+ on immunohistochemistry). Restaging CT scan of the chest, abdomen, and pelvis revealed new 4- to 6-mm pulmonary nodules, hilar and mediastinal lymphadenopathy, new liver lesions, and bone lesions. Nuclear bone scan confirmed multiple bone metastases of the right and left iliac bones and sternum. Complete blood cell count with differential and complete metabolic panel were within normal ranges. The CA 27-29 tumor marker for breast cancer was elevated at 495 U/mL (normal range, < 37 U/mL). DE was understandably devastated by the new diagnosis. She questioned how the treatment plan was to be established. Her medical oncologist struck a somewhat optimistic tone. He explained that metastatic breast cancer was not yet considered to be curable, but periods of disease stability and chronicity were possible. He explained that the HER2 positivity was perhaps the most important factor in delineating her treatment options. He told her that current treatment options were numerous and increasing in number.}, } @article {pmid29873455, year = {2017}, author = {Mileski, M and Ayala, L and Campuzano, E and Joy, A and Ornelas, S and Ortiz, M and Saenz, J}, title = {Quality of Life Considerations During Cancer Treatment in Invasive Ductal Carcinoma Patients: A Systemic Review.}, journal = {The ABNF journal : official journal of the Association of Black Nursing Faculty in Higher Education, Inc}, volume = {28}, number = {1}, pages = {9-13}, pmid = {29873455}, issn = {1046-7041}, mesh = {Female ; Humans ; *Breast Neoplasms/psychology/therapy ; *Carcinoma, Ductal, Breast/psychology/therapy ; *Quality of Life ; }, abstract = {Breast cancer is the number two leading cause of death in women all over the world and is often associated with poor quality of life (QOL). The positive and negative QOL factors influence the overall health and well-being of those affected with invasive ductal carcinoma (IDC). This literature review was structured to identify and understand both the positive and negative QOL factors throughout breast cancer treatment, as well as post breast cancer treatment. Systemic searches were done of three databases to gather data in breast cancer treatment from 2010-2015. Results identified the positive and negative factors associated with the QOL in relation to breast cancer treatment. The most prevalent positive QOL factors included patient expectations, decreased side effects, and increased survival rate. The most prevalent negative QOL factors included treatment, specific side effects and decreased quality of life. This review may guide healthcare professionals in incorporating new practices and identifying the best regimen to improving QOL. The positive and negative QOL factors, in relation to treatment, are important because they help healthcare professionals understand how those factors impact the overall health and well-being of individuals with IDC.}, } @article {pmid29767863, year = {2017}, author = {Zhang, Y and Dang, S and Wan, Y and Yang, F and Li, T}, title = {Influence of VEGF, COX-2, and MMP-9 expression on the molybdenum-targeted X-ray in breast cancer.}, journal = {European journal of gynaecological oncology}, volume = {38}, number = {1}, pages = {45-48}, pmid = {29767863}, issn = {0392-2936}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*metabolism ; Carcinoma, Ductal, Breast/diagnostic imaging/*metabolism ; Cyclooxygenase 2/*metabolism ; Female ; Humans ; Mammography ; Matrix Metalloproteinase 9/*metabolism ; Middle Aged ; Molybdenum ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {AIM: To investigate the correlation of the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and matrix metalloprotease-9 (MMP-9) in breast cancer tissues with molybdenum-targeted X-ray images.

MATERIALS AND METHODS: Sixtynine patients with invasive ductal carcinoma of the breast confirmed by molybdenum-targeted mammography, surgical, and pathologic examinations were enrolled. The expression of VEGF, COX-2, and MMP-9 were detected by immunohistochemical staining (IHS) and the correlation of VEGF, COX-2, and MMP-9 expression and classification of breast cancer on molybdenum-targeted X-ray was statistically analyzed.

RESULTS: The expression of VEGF, COX-2, and MMIP-9 were significantly higher (p < 0.05) in spiculation group (n = 50), vascular abnormalities group (n = 21), and lymph node metastasis group (n = 29),than the other three groups, respectively. However, the expression of VEGF, COX-2, and MMP-9 had no significant differences (p > 0.05) between the group with (n = 30) and without (n = 39) calcification.

CONCLUSION: Expression of VEGF, COX-2, and MMP-9 is highly correlated to the mammaographic appearance of spiculation, vascular abnormalities, and lymph node metastasis. However, the present results suggest that expression of VEGF, COX-2, and MMP-9 is either not or weakly correlated to mammographic appereance of calcification.}, } @article {pmid29787025, year = {2016}, author = {Kasap, E and Gene, M and Sahin, N and Sivrikoz, ON}, title = {Mayer-Rokitansky-Kuster-Hauser syndrome accompanied by invasive ductal carcinoma: a case report.}, journal = {European journal of gynaecological oncology}, volume = {37}, number = {5}, pages = {744-746}, pmid = {29787025}, issn = {0392-2936}, mesh = {46, XX Disorders of Sex Development/*complications/pathology ; Adult ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Congenital Abnormalities/pathology ; Female ; Humans ; Mullerian Ducts/*abnormalities/pathology ; }, abstract = {Milllerian agenesis and the absence of organs of Millerian canal origin are referred to as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Invasive ductal carcinoma constitutes 47-75% of all breast carcinomas and is the most common type. The authors report the first case of invasive ductal carcinoma associated with MRKH syndrome in the literature to their knowledge. A 25-year-old woman with a palpable mass in her right breast for three months presented to the presented clinic. On physical examination a mobile, firm mass measuring 2x2 cm was detected in right breast, at a region close to axilla. A fine needle aspiration biopsy from the lesion revealed malignant cells and thus a segmental mastectomy operation was performed. All genital tract and endocrinological system should be thoroughly examined before administering hormone replacement therapy to patients presenting with primary amenorrhea.The co-occurrence MRKH syndrome of with invasive ductal carcinoma is regarded as coincidental. Confirming the absence of a common etiology, however, requires further genetic studies.}, } @article {pmid30363658, year = {2015}, author = {Shimpi, TR and Baksa Reynolds, V and Shikhare, S and Srinivasan, S and Clarke, MJ and Peh, WCG}, title = {Synchronous large tumoral pseudoangiomatous stromal hyperplasia (PASH) in the breast and axilla with subsequent carcinoma in the contralateral breast: routine and strain imaging with histopathological correlation.}, journal = {BJR case reports}, volume = {1}, number = {3}, pages = {20150017}, pmid = {30363658}, issn = {2055-7159}, abstract = {Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast disorder with the tumoral variety being extremely rare. We report a rare case of synchronous, massive axillary and breast tumoral PASH in a 55-year-old post-menopausal woman. Mammography, ultrasonography and sonoelastography features are illustrated with histopathological correlation. A high-grade invasive ductal carcinoma was detected in the contralateral breast on annual follow-up imaging. Radiologists need to be familiar with the imaging appearances of PASH and be aware of its association with subsequent cancer risk. To the best of our knowledge, the present case of synchronous tumoral PASH in the breast and axillary tissue is the second reported case till now.}, } @article {pmid30363595, year = {2015}, author = {Picillo, M and De Rosa, A and Pellecchia, MT and Criscuolo, C and Amboni, M and Erro, R and Bonifati, V and De Michele, G and Barone, P}, title = {Olfaction in Homozygous and Heterozygous SYNJ1 Arg258Gln Mutation Carriers.}, journal = {Movement disorders clinical practice}, volume = {2}, number = {4}, pages = {413-416}, pmid = {30363595}, issn = {2330-1619}, abstract = {Hyposmia is a common nonmotor symptom in Parkinson's disease (PD) and has been variably detected in monogenic parkinsonism. SYNJ1 has been recently identified as the gene defective in a novel form of autosomal-recessive, early-onset atypical parkinsonism, designed as PARK20. To assess olfaction in PARK20, we administered the University of Pennsylvania Smell Identification Test (UPSIT) in four groups of subjects: SYNJ1 homozygous (HOM = 3) and heterozygous (HET = 4); sporadic PD (PD = 68); and healthy control subjects (CTR = 61). A linear regression model was constructed to assess the association between raw UPSIT score (outcome) and group (HOM, HET, PD, and CTR), adjusting for age, gender, and current smoking status. Likewise in PD patients, odor identification is impaired in homozygous SYNJ1 mutation carriers. Although the limited sample size precludes definite conclusions about olfaction in SYNJ1-related parkinsonism, our findings suggest new insights into PARK20 phenotype and pathophysiology.}, } @article {pmid30713866, year = {2014}, author = {Giordano, A and Amboni, M and Tessitore, A}, title = {Valproate-Induced Generalized Choreoathetosis.}, journal = {Movement disorders clinical practice}, volume = {1}, number = {3}, pages = {271-272}, pmid = {30713866}, issn = {2330-1619}, } @article {pmid31051870, year = {2010}, author = {Machtoub, L and Pfeiffer, R and Backovic, A and Frischauf, S and Wick, MC}, title = {Molecular Imaging Cellular SPIO Uptake with Nonlinear Optical Microscopy.}, journal = {Journal of medical imaging and radiation sciences}, volume = {41}, number = {3}, pages = {159-164}, doi = {10.1016/j.jmir.2010.08.001}, pmid = {31051870}, issn = {1876-7982}, abstract = {We report a novel application to demonstrate and visualize the selective binding of lipids in cells of the reticuloendothelial system to super paramagnetic iron oxide (SPIO) nanoparticles. Ten New Zealand White rabbits that were experimentally injected intravenously with SPIO and five controls were investigated with vibrational microspectroscopy based on surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy. Marked cellular intensity enhancements in hepatic Kupffer cells and melanomacrophages of spleen have been observed in the range of 2850-2875 cm[-1] in SPIO-injected animals but not in controls. The enhancements are related to the selective association of lipid molecules in cells of the reticuloendothelial system to uptaken SPIO, which can uniquely be visualized with SECARS microscopy.}, } @article {pmid30397402, year = {2009}, author = {Ilhan, E and Bati, B and Alemdar, A and Coskun, A and Sezgin, A and Yildirim, M and Engin, O and Purten, M}, title = {A Clinicopathological Evaluation of Male Patients with Breast Cancer.}, journal = {Breast care (Basel, Switzerland)}, volume = {4}, number = {5}, pages = {308-314}, pmid = {30397402}, issn = {1661-3791}, abstract = {BACKGROUND: Although male breast cancer constitutes only 1% of all breast cancers, its incidence is increasing and it is becoming an important public health issue. The present study aims to present the clinicopathological characteristics of surgically treated male breast cancer patients from multiple centers.

PATIENTS AND METHODS: Twenty-one male patients operated on for breast cancer were retrospectively examined in terms of clinical presentation, pathological characteristics, TNM staging status, and type of surgical treatment.

RESULTS: The mean age of the 21 patients was 62.3 years (range 38-94), with the majority being in the range of 50-69 years (61.9%). The most frequent finding was breast mass (85.7%). Most patients underwent modified radical mastectomy (76.1%), and the most prevalent histological type was invasive ductal carcinoma (85.7%). The majority of patients had stage II or III disease, and estrogen receptors were positive in 18 (85.7%) of the patients.

CONCLUSION: Since male breast cancer is a rare condition, it is challenging to conduct prospective randomized trials. Currently, there is a lack of comprehensive data on the diagnosis and management of this condition. Thus, further studies and the implementation of specific guidelines or protocols for this subgroup of patients will aid better management.}, } @article {pmid31159098, year = {1996}, author = {Yu, FY and Chu, FS}, title = {Production and Characterization of Antibodies against Fumonisin B1.}, journal = {Journal of food protection}, volume = {59}, number = {9}, pages = {992-997}, doi = {10.4315/0362-028X-59.9.992}, pmid = {31159098}, issn = {1944-9097}, abstract = {Polyclonal antibodies against fumonisin B1 (FmB1) were produced in rabbits after immunizing the animals with either FmBl-keyhole limpet hemocyanin (KLH) or FmB1 bovine serum albumin (BSA). A direct competitive enzyme-linked immunosorbent assay (dc-ELISA) and an indirect competitive ELISA (idc-ELISA) were used for the characterization of the antibodies and for analysis of the toxin in corn samples. The antibody titers in the serum of rabbits immunized with FmBl-KLH were considerably higher than in those immunized with FmBl-BSA. The antibodies from the rabbits immunized with FmBl-KLH were further characterized. The concentrations causing 50% inhibition of binding of FmB1-horseradish peroxidase (HRP) to the antibodies by FmB1, FmB2 and FmB3 in the ELISA were found to be 0.45, 0.72, and 25 ng/ml, respectively. The detection limit of FmBl, based on 95% confidence at 5% of inhibition of binding of FmBl-HRP conjugate, in buffer of the dc-ELISA was found to be 0.05 ng/ml. In the presence of a matrix such as corn, the detection limit was less than 50 ppb. The overall analytical recoveries of FmBl (50 to 1,000 ng/g) added to the ground corn and then extracted with CH3CN/H2O (1/1, vol/vol) with cleanup and without cleanup in the dc ELISA were found to be 70.5 and 85.9%, respectively. A good correlation was found between the FmBl levels in 2 starch and 10 naturally contaminated corn samples analyzed by the dc-ELISA and the high-pressure liquid chromatography (HPLC) method. The correlation coefficients between ELISA and HPLC were found to be 0.955 (y [ELISA] = 1.3 1x [HPLC] + 77 ppb; P < 0.001) and 0.811 (y = 1.13x + 34 ppb; P < 0.01) for the sample without and with cleanup treatment, respectively.}, } @article {pmid29536376, year = {2018}, author = {Adachi, Y and Sawaki, M and Hattori, M and Yoshimura, A and Gondo, N and Kotani, H and Iwase, M and Kataoka, A and Onishi, S and Sugino, K and Terada, M and Horisawa, N and Mori, M and Oze, I and Iwata, H}, title = {Comparison of sentinel lymph node biopsy between invasive lobular carcinoma and invasive ductal carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {25}, number = {5}, pages = {560-565}, doi = {10.1007/s12282-018-0852-x}, pmid = {29536376}, issn = {1880-4233}, mesh = {Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Micrometastasis/pathology ; Sentinel Lymph Node/pathology ; Sentinel Lymph Node Biopsy/*methods ; }, abstract = {BACKGROUND: Recent studies suggested that ALND (axillary lymph node dissection) can be avoided in breast cancer patients with limited SLN (sentinel lymph node) metastasis. However, these trials included only several invasive lobular carcinoma (ILC) cases, and the validity of omitting ALND for ILC remains controversial. Here, we examined whether omitting ALND is feasible in ILC treatment.

METHODS: A total of 3771 breast cancer patients underwent surgery for breast cancer at the Aichi Cancer Center Hospital between January 2006 and December 2015. We excluded patients with neoadjuvant therapy or without axillary management, and identified 184 ILC patients and 2402 invasive ductal carcinoma (IDC) patients. We compared SLN and non-SLN metastasis rates and the number of total ALN metastases between the ILC and IDC cohorts, and we examined the factors that influenced non-SLN metastasis in the SLN micrometastasis group.

RESULTS: SLN biopsies were performed in 171 (93%) ILC and 2168 (90%) IDC cases, and 31 (18%) ILC and 457 (21%) IDC cases were SLN micrometastasis and macrometastasis (p = 0.36). Among SLN macrometastasis patients, 17 (68%) ILC cases and 163 (46%) IDC cases showed non-SLN metastasis (p = 0.03). The number of non-SLN metastases was greater in ILC cases compared with IDC cases. Multivariate analysis showed that ILC was the influential factor predicting non-SLN metastasis in patients with SLN macrometastasis.

CONCLUSION: ILC cases had more non-SLN metastasis than IDC cases among SLN-positive cases, and ILC was an important factor for the prediction of non-SLN positivity in SLN macrometastasis cases. Omitting ALND for ILC with positive SLNs requires more consideration.}, } @article {pmid29534682, year = {2018}, author = {David, D and Surendran, A and Thulaseedharan, JV and Nair, AS}, title = {Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {284}, pmid = {29534682}, issn = {1471-2407}, mesh = {Adaptor Proteins, Signal Transducing/*chemistry/metabolism ; Breast Neoplasms/metabolism/*pathology ; Cell Proliferation ; Cell Transformation, Neoplastic/metabolism/*pathology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Proteasome Endopeptidase Complex/*metabolism ; Protein Interaction Maps ; Protein Processing, Post-Translational ; Protein Stability ; Proteins/*metabolism ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination ; }, abstract = {BACKGROUND: Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer.

METHODS: Here we demonstrate a novel interaction of CNKSR2 with Smurf2 by co-immunoprecipitation, indirect immunofluorescence studies, and surface plasmon resonance (SPR) analysis, which can ubiquitinate, but stabilize CNKSR2 by protecting it from proteasome mediated degradation.

RESULTS: CNKSR2 protein levels were significantly increased upon forced overexpression of Smurf2, indicating the role of Smurf2 in regulating the stability of CNKSR2. Conversely, Smurf2 knockdown resulted in a marked decrease in the protein level expression of CNKSR2 by facilitating enhanced polyubiquitination and proteasomal degradation and reduced the proliferation and clonogenic survival of MDA-MB-231 breast cancer cell lines. Tissue microarray data from 84 patients with various stages of mammary carcinoma, including (in order of increasing malignant potential) normal, usual hyperplasia, fibrocystic changes, fibroadenoma, carcinoma-in-situ, and invasive ductal carcinoma showed a statistically significant association between Smurf2 and CNKSR2 expression, which is also well correlated with the ER, PR, and HER2 status of the tissue samples. A comparatively high expression of Smurf2 and CNKSR2 was observed when the expression of ER and PR was low, and HER2 was high. Consistently, both Smurf2 and CNKSR2 showed an integrated expression in MCF10 breast progression model cell lines.

CONCLUSIONS: Altogether, our findings reveal that Smurf2 is a novel positive regulator of CNKSR2 and suggest that Smurf2-CNKSR2 interaction may serve as a common strategy to control proliferation of human breast cancer cells by modulating CNKSR2 protein stability.}, } @article {pmid29532340, year = {2018}, author = {Chou, WYY and Veis, DJ and Aft, R}, title = {Radial scar on image-guided breast biopsy: is surgical excision necessary?.}, journal = {Breast cancer research and treatment}, volume = {170}, number = {2}, pages = {313-320}, pmid = {29532340}, issn = {1573-7217}, mesh = {Adult ; Axilla/pathology ; Biomarkers, Tumor ; *Biopsy, Large-Core Needle/methods ; Breast Neoplasms/*diagnosis/metabolism/mortality/surgery ; Cicatrix/*pathology ; Female ; Humans ; *Image-Guided Biopsy ; Middle Aged ; Odds Ratio ; Prognosis ; Sentinel Lymph Node/pathology ; Tumor Burden ; }, abstract = {PURPOSE: Radial scar's stellate appearance may mimic carcinoma mammographically and histologically. Management of radial scar (RS) found on breast core needle biopsies (CNB) ranges from excision to clinical observation due to the variation in reported upgrades to malignancy at surgical excision. We examined the upgrade rate in patients with RS detected on CNB at our institution and reviewed the current literature.

METHODS: A retrospective study was conducted of all cases with RS diagnosed on CNB between December 2006 and March 2017 at our institution. Inclusion criteria were patients with "pure" RS and RS associated with high-risk lesions (HRL). Upgrade was defined as invasive or non-invasive cancer in the excisional biopsy.

RESULTS: 157 cases were identified with RS on CNB, and 122 cases met inclusion criteria. Of these 122 cases, 91 (75%) had pure RS on CNB while 31 (25%) had associated atypia or HRL. 81 (66%) of patients proceeded to excisional biopsy and 41 (34%) did not. Two patients (1.6% of total) were found to have a low-grade invasive ductal carcinoma (0.6 and 0.8 cm) upon surgical excision. None of the remaining 120 patients developed an ipsilateral breast cancer with a mean of 32.3-month follow-up.

CONCLUSIONS: We found a very low upgrade rate to breast cancer when RS was found on CNB with or without associated HRL. Our results are consistent with other reported series. Our data do not support surgical excision for RS but rather close clinical follow-up for patients with RS on CNB.}, } @article {pmid29528718, year = {2018}, author = {Kizy, S and Huang, JL and Marmor, S and Blaes, A and Yuan, J and Beckwith, H and Tuttle, TM and Hui, JYC}, title = {Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.}, journal = {Archives of pathology & laboratory medicine}, volume = {142}, number = {6}, pages = {735-741}, doi = {10.5858/arpa.2017-0169-OA}, pmid = {29528718}, issn = {1543-2165}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/classification/epidemiology/*genetics/pathology ; Epidemiological Monitoring ; Female ; Humans ; Logistic Models ; Middle Aged ; Receptor, ErbB-2/*genetics ; Risk Factors ; United States/epidemiology ; Young Adult ; }, abstract = {CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain.

OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database.

DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database. Recurrence scores were categorized into risk groups using both traditional and Trial Assigning Individualized Options for Treatment cutoffs. Multivariable logistic regression was used to determine factors associated with high-risk RS.

RESULTS: - We identified 45 618 patients with stage I to III, estrogen receptor-positive, HER2-negative breast cancer who had RS available. Overall, 3087 (7%) and 6337 (14%) of cancers were classified as high risk based on traditional and Trial Assigning Individualized Options for Treatment RS cutoffs, respectively. The proportion of high-risk RS ranged from 1% (tubular, 2 of 225) to 68% (medullary, 13 of 19) and 4% (tubular, 10 of 225) to 79% (medullary, 15 of 19) for traditional and Trial Assigning Individualized Options for Treatment cutoffs, respectively. Based on multivariable logistic regression (excluding medullary), subtypes other than invasive ductal carcinoma and papillary carcinoma were significantly associated with lower RS. The strongest predictors of a high-risk RS were higher tumor grade and negative progesterone receptor status.

CONCLUSIONS: - We identified distinct distributions of RS among different histologic subtypes of breast cancer. Excluding medullary carcinoma, histologic subtypes other than invasive ductal carcinoma and papillary carcinoma all predict lower RS.}, } @article {pmid29527071, year = {2018}, author = {Cislak, A and Formanowicz, M and Saguy, T}, title = {Bias against research on gender bias.}, journal = {Scientometrics}, volume = {115}, number = {1}, pages = {189-200}, pmid = {29527071}, issn = {0138-9130}, abstract = {The bias against women in academia is a documented phenomenon that has had detrimental consequences, not only for women, but also for the quality of science. First, gender bias in academia affects female scientists, resulting in their underrepresentation in academic institutions, particularly in higher ranks. The second type of gender bias in science relates to some findings applying only to male participants, which produces biased knowledge. Here, we identify a third potentially powerful source of gender bias in academia: the bias against research on gender bias. In a bibliometric investigation covering a broad range of social sciences, we analyzed published articles on gender bias and race bias and established that articles on gender bias are funded less often and published in journals with a lower Impact Factor than articles on comparable instances of social discrimination. This result suggests the possibility of an underappreciation of the phenomenon of gender bias and related research within the academic community. Addressing this meta-bias is crucial for the further examination of gender inequality, which severely affects many women across the world.}, } @article {pmid29522808, year = {2018}, author = {Levy, DA and Mika, R and Radzyminski, C and Ben-Zvi, S and Tibon, R}, title = {Behavioral reconsolidation interference with episodic memory within-subjects is elusive.}, journal = {Neurobiology of learning and memory}, volume = {150}, number = {}, pages = {75-83}, pmid = {29522808}, issn = {1095-9564}, support = {MC_UU_00005/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Cues ; Female ; Humans ; Male ; Memory Consolidation/*physiology ; *Memory, Episodic ; Mental Recall/*physiology ; Photic Stimulation ; Young Adult ; }, abstract = {In studies of behavioral reconsolidation interference, reactivation of a consolidated memory using some form of reminder is followed by the presentation of new information that can cause interference with that memory. Under these conditions, the interference not only impairs retrieval by indirect processes such as cue interference, but supposedly disrupts the original memory trace directly. Almost all studies of behavioral reconsolidation interference in episodic memory in humans have employed between-subjects paradigms, and deduced reminder effects from intrusion errors. Such studies might introduce confounds arising, for example, from differences in retrieval strategies engendered by the pre-test treatments. We therefore set out to examine whether behavioral reconsolidation interference in episodic memory might be demonstrated within-subjects and by direct memory strength rather than intrusion errors. In three separate experiments, we attempted to disrupt reconsolidation of episodic object-picture memory using a reminder + retroactive interference manipulation. We applied the manipulation over three consecutive days, using a forced-choice recognition test without intrusions from interfering learning, keeping all other study and test parameters constant. No effects of reminder-potentiated interference were observed for measures of accuracy, response times, subjective expressions of recollection, or levels of confidence, as substantiated by Bayesian analyses. These results highlight the difficulty of observing clear behavioral reconsolidation interference effects within-subjects in human episodic memory, and provide some indications of what might be boundary conditions for its demonstration.}, } @article {pmid29517166, year = {2018}, author = {Hagar, A and Flynn, S and Patterson, K and Haddad, F}, title = {Muscular endurance and progression rates of early-stage invasive ductal carcinoma: A pilot study.}, journal = {The breast journal}, volume = {24}, number = {5}, pages = {849-851}, pmid = {29517166}, issn = {1524-4741}, support = {R01 GM122424/GM/NIGMS NIH HHS/United States ; JCITR Pilot Grant, 2016//Indiana University/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/blood/*therapy ; Carcinoma, Ductal, Breast/blood/*therapy ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Lactic Acid/blood ; Middle Aged ; Muscle Strength/*physiology ; Physical Endurance/*physiology ; Pilot Projects ; Retrospective Studies ; }, } @article {pmid29516978, year = {2018}, author = {Li, F and Ren, Y and Wang, Z}, title = {Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters.}, journal = {Journal of cancer research and therapeutics}, volume = {14}, number = {1}, pages = {150-154}, doi = {10.4103/jcrt.JCRT_602_17}, pmid = {29516978}, issn = {1998-4138}, mesh = {Adult ; Aged ; B7-H1 Antigen/*genetics/metabolism ; *Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; }, abstract = {OBJECTIVE: To evaluate the expression of programmed death 1 ligand 1 (PD-L1) in the cancer tissues and tumor-adjacent normal tissues of patients with invasive ductal carcinoma of the breast and to analyze the relationship between the expression of PD-L1 and the clinicopathological features of patients.

MATERIALS AND METHODS: This study included 112 cases of patients with invasive ductal carcinoma of breast who received surgical treatment from March 2012 to February 2016 in Xuzhou Cancer Hospital. The clinical materials of included patients were retrospectively analyzed. The immunohistochemical assay and real-time polymerase chain reaction (PCR) assay were applied to examine the expression of mRNA and protein of PD-L1 in breast cancer specimens of 112 cases and paired tumor-adjacent tissue specimens of 57 cases. The relationship between PD-L1 protein expression and clinicopathological features of patients was analyzed.

RESULTS: PD-L1 protein was mainly expressed in the cytoplasm. The positive rate of PD-L1 expression in invasive ductal carcinoma was 19.6% (22/112), and the positive rate of PD-L1 expression of tumor-adjacent normal tissues was 3.5% (2/57), indicating that the positive rate of PD-L1 expression of cancerous tissues was significantly higher than that of in tumor-adjacent normal tissues (P < 0.05); the positive expression of PD-L1 was not related with the patients' age, menopause history, family history of breast cancer, tumor size, and location of the tumor (P > 0.05) while it was related with lymph node metastasis, the clinic staging, and histopathological grading (P < 0.05). Real-time PCR was applied to detect the mRNA expression of PD-L1 in breast-invasive ductal carcinoma with the mean ΔCt value of 7.79 ± 2.25. However, the mRNA expression of PD-L1 in normal tumor-adjacent tissues was of low expression with the mean ΔCt value of 12.37 ± 3.33. The difference was statistically significant (P< 0.05).

CONCLUSION: The expression of PD-L1 in breast-invasive ductal carcinoma was significantly increased, and it was related to histological grading, clinical staging, and lymph node metastasis of breast cancer. PD-L1 may be a significant marker for the prognosis of breast cancer patients.}, } @article {pmid29514115, year = {2019}, author = {Shaver, PR and Mikulincer, M and Cassidy, J}, title = {Attachment, caregiving in couple relationships, and prosocial behavior in the wider world.}, journal = {Current opinion in psychology}, volume = {25}, number = {}, pages = {16-20}, doi = {10.1016/j.copsyc.2018.02.009}, pmid = {29514115}, issn = {2352-2518}, mesh = {Caregivers/*psychology ; Family Characteristics ; Humans ; Interpersonal Relations ; Models, Psychological ; *Object Attachment ; Psychological Theory ; Social Support ; }, abstract = {According to attachment theory, a sense of attachment security (confidence that others will be available and supportive when needed) facilitates the functioning of the caregiving behavioral system and the empathic provision of care to suffering others. In this article we review what has been learned during the last decade about attachment-related individual differences in caregiving within couple relationships and prosocial behavior in the wider world. We begin with a brief account of attachment theory and the dynamic interplay of the attachment and caregiving behavioral systems. We then review findings from correlational and experimental studies showing that attachment security has positive influences on noticing and reacting favorably to the suffering of romantic partners and strangers.}, } @article {pmid29513137, year = {2018}, author = {Ein-Dor, T and Verbeke, WJMI and Mokry, M and Vrtička, P}, title = {Epigenetic modification of the oxytocin and glucocorticoid receptor genes is linked to attachment avoidance in young adults.}, journal = {Attachment & human development}, volume = {20}, number = {4}, pages = {439-454}, doi = {10.1080/14616734.2018.1446451}, pmid = {29513137}, issn = {1469-2988}, mesh = {Adult ; *Avoidance Learning ; DNA Methylation/genetics ; *Epigenesis, Genetic ; Female ; Humans ; Interpersonal Relations ; Male ; *Object Attachment ; Receptors, Glucocorticoid/*genetics ; Receptors, Oxytocin/*genetics ; Self Report ; Stress, Psychological ; Young Adult ; }, abstract = {Attachment in the context of intimate pair bonds is most frequently studied in terms of the universal strategy to draw near, or away, from significant others at moments of personal distress. However, important interindividual differences in the quality of attachment exist, usually captured through secure versus insecure - anxious and/or avoidant - attachment orientations. Since Bowlby's pioneering writings on the theory of attachment, it has been assumed that attachment orientations are influenced by both genetic and social factors - what we would today describe and measure as gene by environment interaction mediated by epigenetic DNA modification - but research in humans on this topic remains extremely limited. We for the first time examined relations between intra-individual differences in attachment and epigenetic modification of the oxytocin receptor (OXTR) and glucocorticoid receptor (NR3C1) gene promoter in 109 young adult human participants. Our results revealed that attachment avoidance was significantly and specifically associated with increased OXTR and NR3C1 promoter methylation. These findings offer first tentative clues on the possible etiology of attachment avoidance in humans by showing epigenetic modification in genes related to both social stress regulation and HPA axis functioning.}, } @article {pmid29512735, year = {2018}, author = {Nuvoli, S and Galassi, S and Gelo, I and Rocchitta, G and Fancellu, A and Serra, PA and Madeddu, G and Spanu, A}, title = {The role of molecular breast imaging in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy.}, journal = {Oncology reports}, volume = {39}, number = {5}, pages = {2055-2062}, pmid = {29512735}, issn = {1791-2431}, mesh = {Breast Neoplasms/*drug therapy/surgery ; Female ; Humans ; Molecular Imaging/*methods ; Neoadjuvant Therapy/*methods ; Neoplasm, Residual/*diagnostic imaging ; Predictive Value of Tests ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome ; }, abstract = {The aim of the present study was to investigate the usefulness of molecular breast imaging (MBI) in predicting complete tumor response to treatment and residual tumor extent following neoadjuvant therapy. A consecutive series of 43 female patients with large or locally advanced primary breast cancer, scheduled for surgery following neoadjuvant therapy, was retrospectively reviewed. Prior to surgery, all patients underwent MBI using a high‑resolution semiconductor‑based device for image acquisition. MBI data were correlated with surgical histopathological findings. Spearman's correlation coefficient was calculated to assess differences in residual tumor size with MBI and histopathological examination. From the images obtained using MBI, 7 patients were negative for residual tumors with pathological complete response (specificity, 100%) and positive in 34/36 patients with residual disease (sensitivity, 94.4%), including 26/27 patients with unifocal and 8/9 patients with multicentric/multifocal tumors, 5 of which exhibited multiple microscopic foci scattered in a fibrotic area. Overall accuracy was 95.3% and the positive predictive value (PPV) and negative predictive value (NPV) were 100 and 77.8%, respectively. MBI was false‑negative in one patient with a 2.5‑cm invasive ductal carcinoma located close to the chest wall and in one patient with microscopic foci of epithelial carcinoma. In the patients with unifocal residual tumors, correlation of tumor size between MBI and histopathology was r=0.981 (P<0.0001); however, MBI overestimated the number of lesions in one of these cases. In the patients with multifocal/multicentric tumors, MBI adequately assessed residual tumor extent in 5/8 positive cases, overestimating the number of lesions in one case and underestimating tumor extent in 2 further cases with microscopic foci scattered in a fibrotic area. MBI proved to be a highly accurate diagnostic tool in predicting complete tumor response to neoadjuvant therapy and residual tumor extent, correlating with surgical histopathological findings in 86% of overall cases. A positive result was always associated with the presence of residual disease and MBI tumor size was strongly correlated with histopathological analysis mainly in unifocal residual tumors.}, } @article {pmid29511804, year = {2018}, author = {Kim, SY and Shin, J and Kim, DH and Kim, EK and Moon, HJ and Yoon, JH and You, JK and Kim, MJ}, title = {Correlation between electrical conductivity and apparent diffusion coefficient in breast cancer: effect of necrosis on magnetic resonance imaging.}, journal = {European radiology}, volume = {28}, number = {8}, pages = {3204-3214}, pmid = {29511804}, issn = {1432-1084}, support = {NRF-2017R1A2B4010407//National Research Foundation of Korea/ ; 6-2015-0050//faculty research grant of Yonsei University/ ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diffusion Magnetic Resonance Imaging/*methods ; *Electric Conductivity ; Female ; Humans ; Middle Aged ; Necrosis/*diagnostic imaging ; Regression Analysis ; Retrospective Studies ; }, abstract = {OBJECTIVES: To investigate the correlation between conductivity and ADC in invasive ductal carcinoma according to the presence of necrosis on MRI.

METHODS: Eighty-one women with invasive ductal carcinoma ≥1 cm on T2-weighted fast spin echo sequence of preoperative MRI were included. Phase-based MR electric properties tomography was used to reconstruct conductivity. Mean ADC was measured. Necrosis was defined as an area with very high T2 signal intensity. The relationship between conductivity and ADC was examined using Spearman's correlation coefficient (r). Multiple linear regression analysis was performed to identify factors associated with conductivity or ADC.

RESULTS: In the total group, conductivity showed negative correlation with ADC (r = -0.357, p = 0.001). This correlation was maintained in the subgroup without necrosis (n = 53, r = -0.455, p = 0.001), but not in the subgroup with necrosis (n = 28, r = -0.080, p = 0.687). The correlation between the two parameters was different according to necrosis (r = -0.455 vs -0.080, p = 0.047). HER2 enriched subtype was independently associated with conductivity (p = 0.029). Necrosis on MRI was independently associated with ADC (p = 0.027).

CONCLUSIONS: Conductivity shows negative correlation with ADC that is abolished by the presence of necrosis on MRI.

KEY POINTS: • Electric conductivity showed negative correlation with ADC • However, the correlation was abolished by the presence of necrosis on MRI • HER2-enriched subtype was independently associated with conductivity • Necrosis on MRI was independently associated with ADC.}, } @article {pmid29505681, year = {2018}, author = {Schmitt, FCF and Salgado, E and Friebe, J and Schmoch, T and Uhle, F and Fleming, T and Zemva, J and Kihm, L and Nusshag, C and Morath, C and Zeier, M and Bruckner, T and Mehrabi, A and Nawroth, PP and Weigand, MA and Hofer, S and Brenner, T}, title = {Cell cycle arrest and cell death correlate with the extent of ischaemia and reperfusion injury in patients following kidney transplantation - results of an observational pilot study.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {31}, number = {7}, pages = {751-760}, doi = {10.1111/tri.13148}, pmid = {29505681}, issn = {1432-2277}, mesh = {Biomarkers/blood/urine ; C-Reactive Protein/metabolism ; *Cell Cycle Checkpoints ; *Cell Death ; Cold Ischemia/*adverse effects ; Delayed Graft Function ; Humans ; Keratin-18/blood/urine ; Kidney Transplantation/*adverse effects ; Middle Aged ; Pilot Projects ; Receptor for Advanced Glycation End Products/blood ; Reperfusion Injury/*etiology ; Transplantation Immunology ; }, abstract = {A prolonged cold ischaemia time (CIT) is suspected to be associated with an increased ischaemia and reperfusion injury (IRI) resulting in an increased damage to the graft. In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end products (sRAGE), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) were measured. As a result of prolonged CIT and increased IRI, deceased donor transplantations were shown to suffer from a more distinct cell cycle arrest and necrotic cell death. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 were therefore demonstrated to be of value for the detection of a delayed graft function (DGF), as they improved the diagnostic performance of a routinely used clinical scoring system. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 measurements are potentially suitable for early identification of patients at high risk for a DGF following kidney transplantation from deceased or living donors.}, } @article {pmid29501957, year = {2018}, author = {Shen, L and Zhou, G and Tong, T and Tang, F and Lin, Y and Zhou, J and Wang, Y and Zong, G and Zhang, L}, title = {ADC at 3.0 T as a noninvasive biomarker for preoperative prediction of Ki67 expression in invasive ductal carcinoma of breast.}, journal = {Clinical imaging}, volume = {52}, number = {}, pages = {16-22}, doi = {10.1016/j.clinimag.2018.02.010}, pmid = {29501957}, issn = {1873-4499}, mesh = {Adult ; Aged ; Biomarkers ; Breast/*pathology ; Breast Neoplasms/metabolism/*pathology ; *Carcinoma, Ductal, Breast/metabolism ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; ROC Curve ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate the role of apparent diffusion coefficient (ADC) as an imaging biomarker for invasive ductal carcinoma (IDC) in the breast.

METHODS: Seventy-one patients undergoing 3.0 Tesla DWI were retrospectively enrolled. Correlations between the ADC values and prognostic factors were evaluated.

RESULTS: Multivariate regression analyses showed that Ki67 expression and molecular subtype were independently associated with the ADC. Discriminant analysis excluded the ADC as a good biomarker for subtype, but the mean ADC significantly distinguished Ki67-positive (low ADC) from Ki67-negative (high ADC) lesions, as observed in the in ROC curves, with a diagnostic sensitivity of 1.00 and a cut-off value of 0.97 × 10[-3] mm[2]/s.

CONCLUSION: The ADC may be helpful for predicting Ki67 expression in IDC preoperatively.}, } @article {pmid29495422, year = {2018}, author = {Xu, H and Dorn, GW and Shetty, A and Parihar, A and Dave, T and Robinson, SW and Gottlieb, SS and Donahue, MP and Tomaselli, GF and Kraus, WE and Mitchell, BD and Liggett, SB}, title = {A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans.}, journal = {Journal of personalized medicine}, volume = {8}, number = {1}, pages = {}, pmid = {29495422}, issn = {2075-4426}, support = {P30 DK072488/DK/NIDDK NIH HHS/United States ; P50 HL077107/HL/NHLBI NIH HHS/United States ; R35 HL135736/HL/NHLBI NIH HHS/United States ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is the most common form of non-ischemic chronic heart failure. Despite the higher prevalence of IDC in African Americans, the genetics of IDC have been relatively understudied in this ethnic group. We performed a genome-wide association study to identify susceptibility genes for IDC in African Americans recruited from five sites in the U.S. (662 unrelated cases and 1167 controls). The heritability of IDC was calculated to be 33% (95% confidence interval: 19-47%; p = 6.4 × 10[-7]). We detected association of a variant in a novel intronic locus in the CACNB4 gene meeting genome-wide levels of significance (p = 4.1 × 10[-8]). The CACNB4 gene encodes a calcium channel subunit expressed in the heart that is important for cardiac muscle contraction. This variant has not previously been associated with IDC in any racial group. Pathway analysis, based on the 1000 genes most strongly associated with IDC, showed an enrichment for genes related to calcium signaling, growth factor signaling, neuronal/neuromuscular signaling, and various types of cellular level signaling, including gap junction and cAMP signaling. Our results suggest a novel locus for IDC in African Americans and provide additional insights into the genetic architecture and etiology.}, } @article {pmid29494853, year = {2019}, author = {Mikulincer, M and Shaver, PR}, title = {Attachment orientations and emotion regulation.}, journal = {Current opinion in psychology}, volume = {25}, number = {}, pages = {6-10}, doi = {10.1016/j.copsyc.2018.02.006}, pmid = {29494853}, issn = {2352-2518}, mesh = {Adaptation, Psychological ; *Emotional Regulation ; Empirical Research ; Humans ; Interpersonal Relations ; *Object Attachment ; Surveys and Questionnaires ; }, abstract = {According to attachment theory, individual differences in the availability and responsiveness of close relationship partners, beginning in infancy, and the resulting formation of fairly stable attachment orientations are crucial for understanding the ways people experience and regulate emotions. In this article, we review what has been learned during the last decade about attachment-related individual differences in emotion regulation. We begin with a brief account of the hypothesized links between different forms of attachment insecurity (anxiety, avoidance) and strategies people use in regulating distress and coping with threatening events. We then review findings from correlational and experimental studies showing that individual differences in attachment orientation are reflected in cognitive, behavioral, and neural patterns of emotion regulation.}, } @article {pmid29491580, year = {2017}, author = {Debnath, S}, title = {Preliminary studies on the inhibition potential of Indian domestic curd against coliforms, an emerging periodontal pathogen.}, journal = {Journal of Indian Society of Periodontology}, volume = {21}, number = {5}, pages = {357-365}, pmid = {29491580}, issn = {0972-124X}, abstract = {BACKGROUND: Coliforms colonize in dental plaques via oral route and may lead to systemic complications. Escherichia coli and its lipopolysaccharide-induced periodontitis is an emerging threat. Clinical management necessitates antibiotic regimens with risk of resistance and upsetting the gut. There is urgent need for better, sustainable, and economical alternative.

AIM: To investigate the inhibition of coliforms, a potential periodontopathogen directly by Indian domestic curd (IDC) "in situ".

MATERIALS AND METHODS: Coliforms from natural habitat (Municipal sewage in Agartala, Tripura), a source of infection through food and water, were used as target organism. Domestically prepared curd without any fortification is used to explore its true inhibition potential. Assays of agar well diffusion performed with IDC (ultraviolet sterilized and pH adjusted 6.5) against isolated pure cultures of coliforms. The study protocol nullified effect of organic acids, volatile compounds, bacteriophages, and peroxides in IDC. Peptide nature of inhibitory ingredient was studied by Sodium Dodecyle Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE), urea treatment. Computational phylogenetics revealed structural features of inhibitory ingredient. Statistical comparisons were done by analysis of variance. Second-order polynomial regression was done to evaluate the effect of IDC dilution on coliform inhibition. Mann-Whitney U-test performed to analyze different sample treatments.

RESULTS: Agar well diffusion (sealed bottom wells) shows inhibition of catalase-negative coliforms (confirmed by Gram staining and triple sugar iron agar assay) in pure culture (MacConkey agar). Activity diminished in urea, potentiated in ethylene diamine tetra acetic acid, remains unchanged by heat treatment (121°C, 15 min). SDS-PAGE revealed three distinct peptides (>10-15KDa). Hence, thermostable inhibitory peptides attached to target cell lead to observed activity (titer up to 1204.82 AU/ml with minimum 8 mm inhibition).

CONCLUSIONS: IDC adequately inhibits sewage coliforms and may prevent dental plaques coliform colonization and its associated risks.}, } @article {pmid29488717, year = {2017}, author = {Li, A and Pan, Y and Chen, B and Xia, J and Gan, F and Jin, Y and Zheng, J}, title = {[Association of parameters in dynamic contrast-enhanced MRI using reference region model with prognostic factors and molecular subtypes of breast cancer].}, journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences}, volume = {46}, number = {5}, pages = {505-510}, pmid = {29488717}, issn = {1008-9292}, mesh = {*Breast Neoplasms/diagnostic imaging ; *Carcinoma, Ductal/diagnostic imaging ; *Contrast Media ; Female ; Humans ; *Magnetic Resonance Imaging ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: To investigate the association of parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using reference region model with prognostic factors and molecular subtypes of breast cancer.

METHODS: MRI and pathological data of 50 patients with pathologically confirmed invasive ductal carcinoma of the breast were retrospectively analyzed. Reference region model was applied to analyze pharmacokinetic quantitative parameters including volume transfer constant (RR K[trans]), rate constant (Kep) and the ratio of K[trans] to extracellular space volume (K[trans]/Ve). The associations of the above parameters with prognostic factors and molecular subtypes of breast cancer were analyzed.

RESULTS: RR K[trans] and Kep were significantly higher in patients of histological grade 3 compared with those of histological grade 1 & 2 (all P<0.05); and the patients with estrogen receptor (ER)-negative and/or progesterone receptor (PR)-negative also had higher RR K[trans] and Kep than those with ER-positive or PR-positive (all P<0.05). For immunohistochemistry, RR K[trans] and Kep were significantly higher in triple negative breast cancer compared with luminal type breast cancer (all P<0.05).

CONCLUSIONS: High RR K[trans] and Kep are associated with poor prognosis of breast cancer, and which can also be used to distinguish molecular subtypes of breast cancer.}, } @article {pmid29486255, year = {2019}, author = {Birnbaum, GE and Reis, HT}, title = {Evolved to be connected: the dynamics of attachment and sex over the course of romantic relationships.}, journal = {Current opinion in psychology}, volume = {25}, number = {}, pages = {11-15}, doi = {10.1016/j.copsyc.2018.02.005}, pmid = {29486255}, issn = {2352-2518}, mesh = {Female ; Humans ; Interpersonal Relations ; Libido ; *Love ; Male ; Models, Psychological ; *Object Attachment ; Sexual Partners/*psychology ; }, abstract = {Sexual urges and emotional attachments are not always connected. Still, joint operation of the sexual and the attachment systems is typical of romantic relationships. Hence, within this context, the two systems mutually influence each other and operate together to affect relationship well-being. In this article, we review evidence indicating that sex promotes enduring bonds between partners and provide an overview of the contribution of attachment processes to understanding the sex-relationship linkage. We then present a model delineating the functional significance of sex in relationship development. We conclude by suggesting future directions for studying the dual potential of sex for either deepening attachment to a current valued partner or promoting a new relationship when the existing relationship has become less rewarding.}, } @article {pmid29486216, year = {2019}, author = {Abraham, E and Hendler, T and Zagoory-Sharon, O and Feldman, R}, title = {Interoception sensitivity in the parental brain during the first months of parenting modulates children's somatic symptoms six years later: The role of oxytocin.}, journal = {International journal of psychophysiology : official journal of the International Organization of Psychophysiology}, volume = {136}, number = {}, pages = {39-48}, doi = {10.1016/j.ijpsycho.2018.02.001}, pmid = {29486216}, issn = {1872-7697}, mesh = {Adult ; Amygdala/diagnostic imaging/*physiology ; Cerebral Cortex/diagnostic imaging/*physiology ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Interoception/*physiology ; Magnetic Resonance Imaging ; Male ; Maternal Behavior/*physiology ; *Medically Unexplained Symptoms ; Oxytocin/*metabolism ; *Parent-Child Relations ; Parenting ; Paternal Behavior/*physiology ; Saliva ; }, abstract = {Interoception, the perception and interpretation of one's own bodily signals, is a key aspect of human caregiving that impacts infant health and well-being across life. Interoception relies on limbic structures, mainly the amygdala, and the agranular visceromotor cortex, particularly the anterior insula (AI), that integrate with the oxytocin (OT) system to support interoceptive sensitivity. Here, we used functional magnetic resonance imaging (fMRI) to examine whether interoception sensitivity in the parent's brain during the first months of parenting combines with sensitive parenting and OT-system functionality to predict children's somatic symptoms six years later. We followed 45 primary-caregiving first-time mothers and fathers and their infants across the first six years of parenting. In infancy (Time 1), parents' brain response to infant stimuli was imaged, salivary OT measured, and parent-infant interactions coded for parent sensitivity. In preschool (Time 2), parent and child's OT and parent sensitivity were measured again. At six years (Time 3), parents reported on children's somatic symptoms. Greater activation of the parent's AI bilaterally when his/her child was an infant predicted lower child somatic problems at six years. Parent sensitivity partially mediated the links between parental AI activation and child somatic symptoms. In addition, greater parental bilateral amygdala activity predicted higher child OT levels at 3 years and parental OT moderated the relations between preschoolers' OT and later somatic symptoms. Our findings chart two independent cross-generational pathways from interoception sensitivity in the parent's brain and child somatization. The first defines an evolutionary-ancient path including the amygdala and the OT system that support mammalian attention to arousal modulations in response to social cues; the second, via the AI, implicates higher-order interoceptive representations of bodily responses and affective states that underpins human embodiment.}, } @article {pmid29484663, year = {2018}, author = {Percy, DB and Pao, JS and McKevitt, E and Dingee, C and Kuusk, U and Warburton, R}, title = {Number of nodes in sentinel lymph node biopsy for breast cancer: Are surgeons still biased?.}, journal = {Journal of surgical oncology}, volume = {117}, number = {7}, pages = {1487-1492}, doi = {10.1002/jso.25010}, pmid = {29484663}, issn = {1096-9098}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bias ; Breast Neoplasms/epidemiology/*pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/*pathology/surgery ; Carcinoma, Lobular/epidemiology/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Practice Patterns, Physicians' ; Prognosis ; Prospective Studies ; Sentinel Lymph Node/*pathology/surgery ; Sentinel Lymph Node Biopsy/*methods ; Surgeons/*psychology ; Survival Rate ; }, abstract = {BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the number of lymph nodes removed at SLNB, and what factors might bias a surgeon's decision to remove additional nodes.

METHODS: A prospectively maintained database was reviewed. All patients that had SLNB for primary treatment of breast cancer between January 2012 and March 2016 were identified. Clinicopathologic factors were used to compare the number of LNs and rates of node positivity.

RESULTS: One thousand six hundred and three patients were included. The average number of SLNs, non-SLNs, and total LNs was 2.53, 0.54, 3.08, respectively. Significantly more LNs were removed in age <40 versus age >40 (3.73, 3.04 P < 0.01), invasive versus DCIS (3.13, 2.73 P < 0.001), Grade III versus Grade II (3.42, 2.99 P < 0.01), T2 versus T1 (3.40, 2.96 P < 0.01), and ER- versus ER+ (3.45, 3.05 P < 0.05). SLN positivity was significantly higher (P < 0.05) in invasive versus DCIS (27%, 4%), T2 versus T1 (30%. 17%), Grade II versus Grade I (42%, 18%), and ILC versus IDC (38%, 26%).

CONCLUSIONS: There was a significant difference in the number of lymph nodes removed at SLNB in certain groups however; node positivity was not necessarily higher in these groups. Surgeons must be cognizant of potential bias when performing SLNB.}, } @article {pmid29483450, year = {2018}, author = {Hara, Y and Sakurai, K and Adachi, K and Fujiwara, A and Ono, Y and Waga, E and Hirano, T and Enomoto, K}, title = {[A Case of Advanced Breast Cancer Effectively Treated with Bevacizumab and Letrozole].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {2}, pages = {368-370}, pmid = {29483450}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration & dosage ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Combined Modality Therapy ; Female ; Humans ; Letrozole ; Nitriles/administration & dosage ; Treatment Outcome ; Triazoles/administration & dosage ; }, abstract = {We report a case of primary advanced breast cancer that was locally controlled by treatment with bevacizumab. A 69-yearold woman presented at our hospital complaining of left breast hemorrhage. Her left breast had a large mass with an ulcer, and there was bleeding. Breast ultrasonography showed a large tumor that involved the whole left breast, and some swollen axillary lymph nodes. Breast MRI showed a mass of 77mm and skin invasion around the medial area of the left breast. Histopathological examination indicated invasive ductal carcinoma, ER(+), PgR(+), HER2(-), Ki-67 20%. We diagnosed left breast carcinoma, T4bN1M0, stage III B. She received paclitaxel plus bevacizumab as first-line therapy. Breast MRI showed a reduction in the primary tumor and axillary lymph node swelling. Adverse events including hypertension(Grade 3) and peripheral neuropathy(Grade 2)were observed. She received letrozole as second-line therapy. After commencing letrozole, the tumor reduced further, and the local ulcer disappeared showing only induration. Four years from the start of treatment, the woman has obtained good local control and has not developed other metastases.}, } @article {pmid29483449, year = {2018}, author = {Hara, K and Yoshitomi, S and Tsuji, H}, title = {[A Case of the Locally Advanced Breast Cancer with Serious Comorbidities Obtained a Good Local Control].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {2}, pages = {365-367}, pmid = {29483449}, issn = {0385-0684}, mesh = {Aged ; Biomarkers, Tumor/blood ; Breast Neoplasms/chemistry/pathology/*therapy ; Carcinoma, Ductal, Breast/chemistry/*therapy ; Combined Modality Therapy ; Female ; Humans ; Treatment Outcome ; }, abstract = {A 66-years-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass, associated massive exudates, bleedingand foul-smelling discharge. Invasive ductal carcinoma was diagnosed by core needle biopsy. The computed tomography showed left axillary lymph node metastases and no distant metastasis. Her performance status(PS) was Grade 3. She had serious comorbidities such as non-alcoholic steatohepatitis and liver cirrhosis, renal dysfunction. DMpC therapy and Mohs paste therapy were started since her overall status was improved. The huge left breast tumor and left axillary lymph node metastases were reduced remarkably. Total mastectomy and axillary lymph node dissection and free skin grafting was perfomed, and PS was improved to Grade 0, She received DMpC therapy for 4 months postoperatively, and radiotherapy at left chest wall and supraclavicular fossa.}, } @article {pmid29483434, year = {2018}, author = {Ishizuka, M and Tsubota, Y and Ueda, A and Sueoka, N and Yoshikawa, K and Yamamoto, D}, title = {[Local Control by Mastectomy in Advanced Breast Cancer with Liver Metastasis after Chemotherapy, Radiotherapy, and Hyperthermia - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {2}, pages = {321-323}, pmid = {29483434}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/pathology/*therapy ; Chemoradiotherapy ; Female ; Fever ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; }, abstract = {Advanced breast cancer has a poor prognosis compared to early breast cancer; however, quality of life and radical operation can be improved in some case by using multidisciplinary treatment. A 54-year-old woman was examined at the hospital because of an enlarging tumor in the left breast. She was aware of a lump for 3 years. Results of the initial examination indicated invasive ductal carcinoma with liver metastasis. She first received chemotherapy(AC followed by weekly paclitaxel). After 4 courses of weekly paclitaxel, computed tomography revealed axillary lymph nodes involved in the axillary vein. Operation was difficult and conversion therapy was administered. The patient underwent radiotherapy, hyperthermia, and hormone therapy. After 1 year from the start of hormone therapy, the metastasis had disappeared and the patient underwent operation in our unit. Eight months after operation, no recurrence was observed.}, } @article {pmid29483429, year = {2018}, author = {Takahashi, M and Suematsu, Y and Yamagishi, S and Kanematsu, K and Saitou, H and Nakayama, M and Fukahori, M and Wakabayashi, K and Ito, Y}, title = {[A Case of a Bulky Axillary Ectopic Breast Cancer Which Successfully Resected after Chemotherapy(Docetaxel)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {2}, pages = {306-308}, pmid = {29483429}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Axilla ; Breast Neoplasms/*drug therapy/pathology/surgery ; Docetaxel ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis ; Neoadjuvant Therapy ; Taxoids/*therapeutic use ; }, abstract = {A 78-year-old woman presented with a right axillary mass.With an incisional biopsy a diagnosis of invasive ductal carcinoma was achieved.In the whole body search, any primary focus including the breast was unclear, advanced occult breast cancer with supraclavicular lymph node metastases was diagnosed.Administration of 3 courses of docetaxel achieved disappearance of supraclavicular lymph node and reduction of an axillary mass.Right axillary lymph node dissection could be successfully performed.Pathological report showed a right ectopic cancer with right axillary lymph node metastases.The patient has been well without any relapse for 3 years.}, } @article {pmid29480844, year = {2018}, author = {Wang, X and Jin, M and Ye, Q and Wang, M and Hu, Y and Yang, Y and Yang, J and Cai, J}, title = {Solitary duodenum metastasis from breast cancer with 8 years' latency: A case report.}, journal = {Medicine}, volume = {97}, number = {2}, pages = {e9550}, pmid = {29480844}, issn = {1536-5964}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Duodenal Neoplasms/drug therapy/pathology/*secondary/surgery ; Female ; Humans ; Middle Aged ; }, abstract = {RATIONALE: Advanced breast cancer frequently metastasizes to the lungs, liver, and bones. Metastatic involvement of the duodenal bulb is extremely rare and difficult to detect by endoscopy.

PATIENT CONCERNS: A 51-year-old menopausal woman presented with abdominal fullness and obstructive symptoms, and was diagnosed with adenocarcinoma in the duodenal bulb. The patient had undergone modified radical mastectomy of the left breast for infiltrating ductal carcinoma (IDC) 8 years previously.

DIAGNOSIS: Metastatic infiltration of the duodenal bulb originating from IDC was proven histologically and immunohistochemically.

INTERVENTIONS: She received chemotherapy with docetaxel and capecitabine followed by hormone maintenance therapy with letrozole after operation.

OUTCOMES: After treatment, the patient recovered well. She is currently being followed up.

LESSONS: Patients with known breast cancer history with the IDC histological type and presenting with nonspecific abdominal symptoms or signs, such as abdominal fullness, nausea, and vomiting, should undergo endoscopy with histopathological examination in order to detect possible gastrointestinal metastasis of the primary breast tumor. This report intends to alert people to heed this type of breast cancer metastasis and not treat it as a primary gastrointestinal tumor.}, } @article {pmid29475895, year = {2018}, author = {Rhone, P and Ruszkowska-Ciastek, B and Bielawski, K and Brkic, A and Zarychta, E and Góralczyk, B and Roszkowski, K and Rość, D}, title = {Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients.}, journal = {Bioscience reports}, volume = {38}, number = {2}, pages = {}, pmid = {29475895}, issn = {1573-4935}, mesh = {Aged ; Breast Neoplasms/*blood/pathology ; Female ; Humans ; Lipoproteins/blood ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*blood ; Plasminogen Activator Inhibitor 1/blood ; Thromboplastin/metabolism ; Tissue Plasminogen Activator/blood ; }, abstract = {Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45-66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45-68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.}, } @article {pmid29471435, year = {2018}, author = {Desmedt, C and Salgado, R and Fornili, M and Pruneri, G and Van den Eynden, G and Zoppoli, G and Rothé, F and Buisseret, L and Garaud, S and Willard-Gallo, K and Brown, D and Bareche, Y and Rouas, G and Galant, C and Bertucci, F and Loi, S and Viale, G and Di Leo, A and Green, AR and Ellis, IO and Rakha, EA and Larsimont, D and Biganzoli, E and Sotiriou, C}, title = {Immune Infiltration in Invasive Lobular Breast Cancer.}, journal = {Journal of the National Cancer Institute}, volume = {110}, number = {7}, pages = {768-776}, pmid = {29471435}, issn = {1460-2105}, mesh = {Breast Neoplasms/diagnosis/*immunology/metabolism/*pathology ; Carcinoma, Lobular/diagnosis/*immunology/metabolism/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating/metabolism/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC.

METHODS: We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided.

RESULTS: TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with young age, lymph node involvement, and high proliferative tumors. In the univariate analysis, high TIL levels were associated with worse prognosis in the retrospective and BIG 02-98 lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition.

CONCLUSIONS: This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.}, } @article {pmid29470686, year = {2018}, author = {Fukuda, J and Tanaka, S and Ishida, N and Ioka, T and Ikezawa, K and Takakura, R and Nakao, M and Ohkawa, K and Katayama, K and Nagata, S}, title = {A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal pancreatitis demonstrated by contrast-enhanced ultrasonography.}, journal = {Journal of medical ultrasonics (2001)}, volume = {45}, number = {4}, pages = {617-622}, pmid = {29470686}, issn = {1613-2254}, mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnostic imaging/pathology/surgery ; *Contrast Media ; Early Diagnosis ; Female ; Humans ; *Microbubbles ; Middle Aged ; Neoplasm Staging ; Pancreas/diagnostic imaging/pathology ; Pancreatic Neoplasms/complications/*diagnostic imaging/pathology/surgery ; Pancreatitis/complications/*diagnostic imaging/pathology ; Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {A patient with slight dilatation of the main pancreatic duct was followed-up with ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve years later, a faint hypoechoic area 13 mm in diameter was first detected on the body of the pancreas. Contrast-enhanced ultrasonography revealed a well-demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an unclear margin. The former was suspected to be a small pancreatic cancer lesion, and the latter to be focal pancreatitis accompanying cancer. However, contrast-enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was confirmed with pancreatic juice cytology through endoscopic retrograde pancreatography. Surgical resection was performed, and the lesion was pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm), infiltrative type (pT1), stage IA. When comparing the images from contrast-enhanced ultrasonography with the pathological findings, the hypoenhanced area corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed information on the focal lesion in the pancreas, and it was effective for the early diagnosis of pancreatic cancer.}, } @article {pmid29467930, year = {2018}, author = {Li, C and Luo, L and Wei, S and Wang, X}, title = {Identification of the potential crucial genes in invasive ductal carcinoma using bioinformatics analysis.}, journal = {Oncotarget}, volume = {9}, number = {6}, pages = {6800-6813}, pmid = {29467930}, issn = {1949-2553}, abstract = {Invasive ductal carcinoma (IDC) is a common histological type of breast cancer. The aim of this study was to identify the potential crucial genes associated with IDC and to provide valid biological information for further investigations. The gene expression profiles of GSE10780 which contained 42 histologically normal breast tissues and 143 IDC tissues were downloaded from the GEO database. Functional and pathway enrichment analysis of differentially expressed genes (DEGs) were performed and protein-protein interaction (PPI) network was analyzed using Cytoscape. In total, 999 DEGs were identified, including 667 up-regulated and 332 down-regulated DEGs. Gene ontology analysis demonstrated that most DEGs were significantly enriched in mitotic cell cycle, adhesion and protein binding process. Through PPI network analysis, a significant module was screened out, and the top 10 hub genes, CDK1, CCNB1, CENPE, CENPA, PLK1, CDC20, MAD2L1, HIST1H2BK, KIF2C and CCNA2 were identified from the PPI network. The expression levels of the 10 genes were validated in Oncomine database. KIF2C, MAD2L1 and PLK1 were associated with the overall survival. And we used cBioPortal to explore the genetic alterations of hub genes and potential drugs. In conclusion, the present study identified DEGs between normal and IDC samples, which could improve our understanding of the molecular mechanisms in the development of IDC, and these candidate genes might be used as therapeutic targets for IDC.}, } @article {pmid29461494, year = {2018}, author = {Seimon, RV and Wild-Taylor, AL and Gibson, AA and Harper, C and McClintock, S and Fernando, HA and Hsu, MSH and Luz, FQD and Keating, SE and Johnson, NA and Grieve, SM and Markovic, TP and Caterson, ID and Byrne, NM and Sainsbury, A}, title = {Less Waste on Waist Measurements: Determination of Optimal Waist Circumference Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with Obesity.}, journal = {Nutrients}, volume = {10}, number = {2}, pages = {}, pmid = {29461494}, issn = {2072-6643}, mesh = {*Adiposity ; Aged ; Anthropometry/*methods ; Female ; Humans ; Intra-Abdominal Fat/*diagnostic imaging/physiopathology ; *Magnetic Resonance Imaging ; Middle Aged ; Obesity/*diagnosis/diagnostic imaging/physiopathology ; *Postmenopause ; Predictive Value of Tests ; Reproducibility of Results ; *Waist Circumference ; }, abstract = {With obesity being a leading cause of preventable death, it is vital to understand how best to identify individuals with greater risk of metabolic disease, especially those with high visceral adipose tissue (VAT). This study aimed to determine whether three commonly used waist circumference (WC) measurement sites could provide accurate estimations of VAT, as determined by magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in postmenopausal women with obesity. VAT volume was measured by MRI of the total abdomen in 97 women aged 57.7 ± 0.4 years (mean ± SEM), mean body mass index 34.5 ± 0.2 kg/m[2]. WC was measured at the midpoint between the lowest rib and the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the level of the umbilicus (WCumbilicus). WC differed significantly according to measurement site, with WCnarrow (102.1 ± 0.7 cm) < WCmid (108.3 ± 0.7 cm) < WCumbilicus (115.7 ± 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and 0.390, respectively; p < 0.001 for all), but the relationships between WCmid or WCnarrow and VAT determined by MRI were stronger than for WCumbilicus. Measurement of either WCmid or WCnarrow provides valid estimates of VAT in postmenopausal women with obesity, with WCnarrow being favoured in light of its greater ease and speed of measurement in this population.}, } @article {pmid29460095, year = {2018}, author = {Saimura, M and Koga, K and Anan, K and Mitsuyama, S and Tamiya, S}, title = {Diagnosis, characteristics, and treatment of breast carcinomas within benign fibroepithelial tumors.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {25}, number = {4}, pages = {470-478}, doi = {10.1007/s12282-018-0847-7}, pmid = {29460095}, issn = {1880-4233}, mesh = {Adult ; Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology/surgery ; Female ; Fibroadenoma/diagnosis/pathology/surgery ; Humans ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Fibroepithelial/*diagnosis/pathology/*surgery ; Phyllodes Tumor/diagnosis/pathology/surgery ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Breast carcinoma arising in a benign fibroepithelial tumor is rare, and is usually discovered incidentally during examination of the breast mass.

METHODS: We evaluated the clinicopathological features, treatment, and prognosis of seven women with breast carcinomas within benign fibroepithelial tumors, diagnosed and treated at a single institution between 2011 and 2015.

RESULTS: Seven women, aged 21-64 years, visited our hospital complaining of a breast mass detected by self-checking or screening examination. All patients had well-demarcated movable breast masses. Ultrasonography showed circumscribed masses suggesting benign tumors in all cases, and mammography revealed well-defined, high-density masses, with or without calcification. The masses progressed in two patients. A preoperative histological diagnosis of carcinoma was made following needle biopsy in four patients. Tumorectomy, breast-conserving surgery, and mastectomy were performed in three, two, and two patients, respectively. One patient underwent lymph node dissection and another underwent sentinel node biopsy. Histologically, the masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ or lobular carcinoma in situ, arising in a benign phyllodes tumor, fibroadenoma, or fibroadenomatoid mastopathy. Lymph node metastasis was detected in two patients. There was no recurrence in any of the patients.

CONCLUSIONS: Although a carcinoma within a preexisting benign fibroepithelial tumor is extremely rare, it is important to be aware of the possibility of invasive and metastatic disease.}, } @article {pmid29456844, year = {2018}, author = {Yigitbasi, T and Calibasi-Kocal, G and Buyukuslu, N and Atahan, MK and Kupeli, H and Yigit, S and Tarcan, E and Baskin, Y}, title = {An efficient biomarker panel for diagnosis of breast cancer using surface-enhanced laser desorption ionization time-of-flight mass spectrometry.}, journal = {Biomedical reports}, volume = {8}, number = {3}, pages = {269-274}, pmid = {29456844}, issn = {2049-9434}, abstract = {Breast cancer (BC) is the most frequently diagnosed cancer that affects women worldwide. Early detection of BC is important to improve survival rates and decrease mortality. The aim of the present study was to investigate serum biomarkers using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to distinguish patients with BC from the healthy population and patients with benign breast diseases (BBDs). A total of 62 patients with invasive ductal carcinoma, as confirmed by histopathology, and 47 non-cancerous individuals (NCIs) [16 healthy controls (HCs) and 31 patients with BBD] were enrolled in the present study. Serum protein profiles were determined by SELDI-TOF-MS using an immobilized metal affinity capture array. Serum from patients with BC were compared with that from the HC group using univariate and multivariate statistical analyses. A total of 118 clusters were generated from the individual serum. Univariate analysis revealed that 5 peaks were significantly downregulated (m/z 1,452, 2,670, 3,972, 5,354 and 5,523; P<0.001) and 4 were upregulated (m/z 6,850, 7,926, 8,115 and 8,143; P<0.001) in patients with BC compared with the HC group. A comparison of patients with BC and patients with BBD revealed an additional 9 protein peaks. Among these, 3 peaks (m/z 3,972, 5,336 and 11,185) were significantly downregulated and 6 peaks (m/z 4,062, 4,071, 4,609, 6,850, 8,115 and 8,133) were significantly upregulated. A total of 3 peaks [mass-to-change ratio (m/z) 3,972, 6,850 and 8,115 (BC2)] were common in both sets. The results of the present study suggest that a 4 protein peak set [m/z 3,972, 6,850 and 8,115 (BC2) and 8,949 (BC3)] could be used to distinguish patients with BC from NCI.}, } @article {pmid29456134, year = {2018}, author = {Kim, H}, title = {Parietal control network activation during memory tasks may be associated with the co-occurrence of externally and internally directed cognition: A cross-function meta-analysis.}, journal = {Brain research}, volume = {1683}, number = {}, pages = {55-66}, doi = {10.1016/j.brainres.2018.01.022}, pmid = {29456134}, issn = {1872-6240}, mesh = {Attention/physiology ; *Brain Mapping ; Cognition/*physiology ; Humans ; Memory, Episodic ; Mental Recall/*physiology ; Neural Pathways/*physiology ; Recognition, Psychology/*physiology ; }, abstract = {Functional neuroimaging studies on episodic memory retrieval consistently indicated the activation of the precuneus (PCU), mid-cingulate cortex (MCC), and lateral intraparietal sulcus (latIPS) regions. Although studies typically interpreted these activations in terms of memory retrieval processes, resting-state functional connectivity data indicate that these regions are part of the frontoparietal control network, suggesting a more general, cross-functional role. In this regard, this study proposes a novel hypothesis which suggests that the parietal control network plays a strong role in accommodating the co-occurrence of externally directed cognition (EDC) and internally directed cognition (IDC), which are typically antagonistic to each other. To evaluate how well this dual cognitive processes hypothesis can account for parietal activation patterns during memory tasks, this study provides a cross-function meta-analysis involving 3 different memory paradigms, namely, retrieval success (hit > correct rejection), repetition enhancement (repeated > novel), and subsequent forgetting (forgotten > remembered). Common to these paradigms is that the target condition may involve both EDC (stimulus processing and motor responding) and IDC (intentional remembering, involuntary awareness of previous encounter, or task-unrelated thoughts) strongly, whereas the reference condition may involve EDC to a greater extent, but IDC to a lesser extent. Thus, the dual cognitive processes hypothesis predicts that each of these paradigms will activate similar, overlapping PCU, MCC, and latIPS regions. The results were fully consistent with the prediction, supporting the dual cognitive processes hypothesis. Evidence from relevant prior studies suggests that the dual cognitive processes hypothesis may also apply to non-memory domain tasks.}, } @article {pmid29453385, year = {2018}, author = {Kim, WH and Lee, SW and Kim, HJ and Chae, YS and Jeong, SY and Jung, JH and Park, HY and Lee, WK}, title = {Prediction of Advanced Axillary Lymph Node Metastases (ypN2-3) Using Breast MR imaging and PET/CT after Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma Patients.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {3181}, pmid = {29453385}, issn = {2045-2322}, mesh = {Adult ; Axilla/pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; Fluorodeoxyglucose F18/metabolism ; Humans ; Image Processing, Computer-Assisted/methods ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Magnetic Resonance Imaging/methods ; Middle Aged ; Multimodal Imaging/*methods ; Neoadjuvant Therapy/methods ; Positron Emission Tomography Computed Tomography/methods ; Positron-Emission Tomography/methods ; ROC Curve ; Radiopharmaceuticals/therapeutic use ; Tomography, X-Ray Computed/methods ; }, abstract = {We aimed to investigate the value of breast magnetic resonance (MR) imaging and positron emission tomography-computed tomography (PET/CT) in predicting advanced axillary lymph node (ALN) metastases (ypN2-3) after neoadjuvant chemotherapy (NAC) in invasive ductal carcinoma patients. A total of 108 patients with invasive ductal carcinoma underwent breast MR imaging and PET/CT both before and after NAC (termed initial staging and restaging, respectively). The number of positive ALNs and the short diameter (SD) of the largest ALN on breast MR imaging and maximal standardized uptake value (SUVmax) in the ALNs on PET/CT were evaluated. Odds ratio (OR) for prediction of advanced ALN metastases was calculated. The negative predictive value (NPV) of restaging imaging for exclusion of advanced ALN metastases was also calculated. Patients with advanced ALN metastases were more likely to have a higher number (≥2) of positive LNs (OR, 8.06; P = 0.015) on restaging MR imaging. No clinico-pathological factors were significantly associated with advanced ALN metastases. With restaging MR imaging, PET/CT, and MR imaging plus PET/CT, the NPV for excluding advanced ALN metastases was 97.3%, 94.4%, and 100.0%. A higher number of positive ALNs on restaging MR imaging was an independent predictor for advanced ALN metastases after NAC.}, } @article {pmid29445299, year = {2018}, author = {Niska, JR and Keole, SR and Pockaj, BA and Halyard, MY and Patel, SH and Northfelt, DW and Gray, RJ and Wasif, N and Vargas, CE and Wong, WW}, title = {Choosing wisely after publication of level I evidence in breast cancer radiotherapy.}, journal = {Breast cancer (Dove Medical Press)}, volume = {10}, number = {}, pages = {31-37}, pmid = {29445299}, issn = {1179-1314}, abstract = {BACKGROUND: Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT. To assess response to level I evidence and adherence to ASTRO recommendations, we evaluated the pattern of RT use for early-stage breast cancer at our National Comprehensive Cancer Network institution from 2006 to 2008 and 2011 to 2013 and compared the results with national trends.

METHODS: Data from a prospective database were extracted to include patients treated with BCT, aged ≥50 years, with histologic findings of invasive ductal carcinoma, stage T1-T2N0M0, estrogen receptor-positive, and HER2 normal. We retrospectively reviewed the medical records and estimated costs based on 2016 Hospital Outpatient Prospective Payment System (technical fees) and Medicare Physician Fee Schedule (professional fees).

RESULTS: Among 55 cases from 2006 to 2008, treatment regimens were 11% hypofractionated, 69% traditional schedule, and 20% RT omission (29% of patients were aged >70 years). Among 83 cases from 2011 to 2013, treatment regimens were 54% hypofractionated, 19% traditional schedule, and 27% RT omission (48% of patients were aged >70 years). 3DCRT was used for all WBRT treatments. Direct medical cost estimates were as follows: 15 fractions 3DCRT, $7,197.87; 15 fractions IMRT, $11,232.33; 25 fractions 3DCRT, $9,731.39; and 25 fractions IMRT, $16,877.45.

CONCLUSION: Despite apparent resistance to shorter radiation schedules in the United States, we demonstrate that rapid practice change in response to level I evidence is feasible. Wider adoption of evidence-based guidelines in early-stage breast cancer may substantially lower health care costs and improve convenience for patients without sacrificing oncologic outcomes.}, } @article {pmid29436376, year = {2018}, author = {Yu, BH and Tang, SX and Xu, XL and Cheng, YF and Bi, R and Shui, RH and Tu, XY and Lu, HF and Zhou, XY and Yang, WT}, title = {Breast carcinoma in sclerosing adenosis: a clinicopathological and immunophenotypical analysis on 206 lesions.}, journal = {Journal of clinical pathology}, volume = {71}, number = {6}, pages = {546-553}, doi = {10.1136/jclinpath-2017-204751}, pmid = {29436376}, issn = {1472-4146}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/genetics ; Biopsy ; Breast Carcinoma In Situ/*chemistry/genetics/pathology/surgery ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology/surgery ; Carcinoma, Lobular/*chemistry/genetics/pathology/surgery ; Diagnostic Errors ; Female ; Fibrocystic Breast Disease/*chemistry/genetics/pathology/surgery ; Humans ; *Immunohistochemistry ; Immunophenotyping/*methods ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; *Sclerosis ; Tumor Burden ; }, abstract = {AIMS: To fully elucidate the clinicopathological features of breast carcinoma in sclerosing adenosis (SA-BC).

METHODS: Clinical and histological characteristics of 206 SA-BCs from 180 patients were retrospectively evaluated. Immunohistochemical phenotype was examined. The clinicopathological relevance of the topographical pattern of SA-BCs was analysed.

RESULTS: Overall, up to 46 patients (25.6%) had contralateral cancer, either SA associated or not. Of 99 cases who underwent core needle biopsy (CNB), 36 were underestimated as adenosis or atypical ductal hyperplasia at CNB, 5 invasive cases were misinterpreted as in situ carcinomas, whereas 4 ductal carcinoma in situ (DCIS) cases were overdiagnosed as invasive carcinoma. Microscopically, 163 tumours were in situ, including 136 DCIS, 19 lobular carcinomas in situ (LCIS) and 8 mixed DCIS/LCIS; of these carcinomas in situ (CIS), 37 had microinvasion. The DCIS group exhibited low, intermediate and high grades in 53.7%, 34.6% and 11.8% of cases, respectively, mostly with solid (43.4%) or cribriform (41.9%) pattern. Forty out of 43 invasive cases were invasive ductal carcinoma (IDC), mostly DCIS predominant. Immunophenotypically, luminal A phenotype was identified in 55.1%, 63.2% and 45.0% of DCIS, LCIS and IDC cases, respectively. Topographical type A group (carcinoma being entirely confined to SA, n=176) was characterised by smaller size, less invasiveness, lower grade and more frequency of luminal A immunophenotype compared with type B group (≥ 50% but not all of the carcinomatous lesion being located in SA, n=30) (all P<0.05).

CONCLUSIONS: CIS, especially non-high-grade DCIS, represents the most common variant of SA-BC, and luminal A is the most predominant immunophenotype. CNB assessment might be challenging in some SA-BCs. The topographical pattern has great clinicopathological relevance. Careful evaluation of the contralateral breast and long-term follow-up for patients with SA-BC is necessary given its high prevalence of bilaterality.}, } @article {pmid29425951, year = {2018}, author = {Roncero, M and Belloch, A and Doron, G}, title = {A novel approach to challenging OCD related beliefs using a mobile-app: An exploratory study.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {59}, number = {}, pages = {157-160}, doi = {10.1016/j.jbtep.2018.01.008}, pmid = {29425951}, issn = {1873-7943}, mesh = {Adult ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; Male ; Mobile Applications ; Obsessive-Compulsive Disorder/*therapy ; *Outcome Assessment, Health Care ; Telemedicine/*methods ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: According to cognitive models, obsessive compulsive symptoms result from catastrophic misinterpretations of commonly occurring intrusive experiences and the use of counterproductive strategies to manage them. Obsessive Compulsive Disorder (OCD) related beliefs such as inflated responsibility, importance of thoughts and perfectionism increases the likelihood of such misinterpretations. Consistent with a growing body of literature supporting the usefulness of mobile delivered technologies in fostering cognitive behavior change, the present study assessed the effectiveness of a novel cognitive training exercise designed to challenge OCD-related beliefs. This mobile app training exercise consists of users having to pull statements challenging OCD beliefs towards themselves (downwards) and to throw away (push upwards) contra-productive self-statements.

METHODS: 36 third-year BA students started the trial. Twenty completed pre and post measures of OCD-beliefs, mood and OCD symptoms including relationship-obsessions. Participants were instructed to complete 3 min of daily training for a period of 15 days.

RESULTS: No significant differences were found between completers and non-completers on demographic and most symptom related measures at Time 1. Repeated-measures MANOVA of the 20 completers showed a significant reduction on all OCD symptoms measures and on OCD-beliefs. No significant reduction was found in depression symptoms. Regression analysis showed change in levels of OCD-beliefs was associated with reduction in OCD symptoms at Time 2 over and above OCD symptoms at Time 1.

LIMITATIONS: The study is an open trial with non-clinical participants.

CONCLUSIONS: This mobile delivered training exercise may be useful for the reduction and relapse prevention of OCD-related beliefs and symptoms.}, } @article {pmid29422258, year = {2018}, author = {Papachristopoulou, G and Papadopoulos, EI and Nonni, A and Rassidakis, GZ and Scorilas, A}, title = {Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status.}, journal = {Clinical breast cancer}, volume = {18}, number = {4}, pages = {305-312.e3}, doi = {10.1016/j.clbc.2017.11.007}, pmid = {29422258}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology/therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/therapy ; Carcinoma, Lobular/genetics/pathology/therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Prognosis ; ROC Curve ; Survival Analysis ; }, abstract = {BACKGROUND: Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR-29b expression in breast tumors and thus explore its clinical value.

MATERIALS AND METHODS: One hundred twenty-one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real-time polymerase chain reaction protocol was developed and miR-29b levels, estimated via the comparative CT method, were finally subjected to comprehensive statistical analysis.

RESULTS: MiR-29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P = .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR-29b expression was elevated in samples with positive estrogen receptor status (P = .021) in the overall population, whereas it was negatively correlated (P = .035) with primary tumor staging in the ductal subset and increased in poorly-differentiated tumors of lobular origin (P = .041). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR-29b levels had a significantly longer disease-free survival (P = .010) and a lower risk to relapse (hazard ratio = 0.35, 95% confidence interval, 0.15-0.81; P = .014).

CONCLUSION: Our results provide evidence that miR-29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.}, } @article {pmid29421830, year = {2019}, author = {Zemva, J and Pfaff, D and Groener, JB and Fleming, T and Herzig, S and Teleman, A and Nawroth, PP and Tyedmers, J}, title = {Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism - What We Know in Mammals and What We Can Learn From Yeast.}, journal = {Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {127}, number = {4}, pages = {203-214}, doi = {10.1055/s-0043-122382}, pmid = {29421830}, issn = {1439-3646}, mesh = {Adipocytes/*metabolism ; Animals ; Diabetes Complications/*metabolism ; Humans ; Insulin-Secreting Cells/*metabolism ; Mammals/*metabolism ; *Oxidative Stress ; Pyruvaldehyde/*metabolism ; *Signal Transduction ; Yeasts/*metabolism ; }, abstract = {Levels of reactive metabolites such as reactive carbonyl and oxygen species are increased in patients with diabetes mellitus. The most important reactive dicarbonyl species, methylglyoxal (MG), formed as by-product during glucose metabolism, is more and more recognized as a trigger for the development and progression of diabetic complications. Although it is clear that MG provokes toxic effects, it is currently not well understood what cellular changes MG induces on a molecular level that may lead to pathophysiological conditions found in long-term diabetic complications. Here we review the current knowledge about the molecular effects that MG can induce in a cell. Within the mammalian system, we will focus mostly on the metabolic effects MG exerts when applied systemically to rodents or when applied in vitro to pancreatic β-cells and adipocytes. Due to the common limitations associated with complex model organisms, we then summarize how yeast as a very simple model organism can help to gain valuable comprehensive information on general defence pathways cells exert in response to MG stress. Pioneering studies in additional rather simple eukaryotic model organisms suggest that many cellular reactions in response to MG are highly conserved throughout evolution.}, } @article {pmid29416801, year = {2018}, author = {More, TH and RoyChoudhury, S and Christie, J and Taunk, K and Mane, A and Santra, MK and Chaudhury, K and Rapole, S}, title = {Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples.}, journal = {Oncotarget}, volume = {9}, number = {2}, pages = {2678-2696}, pmid = {29416801}, issn = {1949-2553}, abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control. Some of the metabolite changes from tissue were also reflected in serum, indicating a bi-directional interaction of metabolites in IDC. Additionally, 8 tissue metabolites and 9 serum metabolites showed progressive change from control to benign to IDC suggesting their possible role in malignant transformation. We have identified a panel of three metabolites viz. tryptophan, tyrosine, and creatine in tissue and serum, which could be useful in screening of IDC subjects from both control and benign. The metabolomic alterations in IDC showed perturbations in purine and pyrimidine metabolism, amino sugar metabolism, amino acid metabolism, fatty acid biosynthesis etc. Comprehensively, this study provides valuable insights into metabolic adaptations of IDC, which can help to identify diagnostic markers as well as potential therapeutic targets.}, } @article {pmid29414744, year = {2018}, author = {Almahayni, T and Vanhoudt, N}, title = {Does leaching of naturally occurring radionuclides from roadway pavements stabilised with coal fly ash have negative impacts on groundwater quality and human health?.}, journal = {Journal of hazardous materials}, volume = {349}, number = {}, pages = {128-134}, doi = {10.1016/j.jhazmat.2018.01.029}, pmid = {29414744}, issn = {1873-3336}, mesh = {Coal Ash/*chemistry ; Construction Materials ; Environment ; Groundwater/*analysis ; Humans ; Radioisotopes/*analysis ; Risk Assessment ; Water Pollutants, Radioactive/*analysis ; }, abstract = {We assessed the potential impact of using coal fly ash to stabilise roadway pavements on groundwater quality and human health. The leaching potential of naturally occurring radionuclides (NORs) typically present in the fly ash was assessed with the HYDRUS-1D code and data representative of a segment of the Wisconsin State Trunk Highway 60 as a case study. Our assessment suggests that the impact would be mainly from the chemical toxicity of uranium (U). In our particular case study, U concentration in the leachate exceeded the maximum contaminant level for this element (MCL = 30 μg L[-1]) in almost all the scenarios. In the groundwater, the MCL was only exceeded under conditions of high leaching and low dilution in the aquifer. The radiological toxicity from the consumption of the contaminated groundwater by a hypothetical adult, however, was at maximum 43% of the individual dose criterion (IDC = 0.1 mSv y[-1]). The results also highlight the need to consider site-specific conditions such as climate and hydrogeology when assessing the environmental impacts of utilising fly ash in roadway construction applications since they could have profound effects on the assessment findings. There is also a pressing need for reliable and representative data to support realistic assessments.}, } @article {pmid29413404, year = {2018}, author = {Cho, WK and Choi, DH and Lee, J and Park, W and Kim, YB and Suh, CO and Shin, KH and Jeon, SH and Kim, K and Park, KR and Kim, JH and Ahn, SJ and Yoon, WS and Yang, DS and Kim, J and Lee, JH and Yea, JW}, title = {Comparison of failure patterns between tubular breast carcinoma and invasive ductal carcinoma (KROG 14-25).}, journal = {Breast (Edinburgh, Scotland)}, volume = {38}, number = {}, pages = {165-170}, doi = {10.1016/j.breast.2018.01.004}, pmid = {29413404}, issn = {1532-3080}, mesh = {Adenocarcinoma/*mortality/pathology ; Adult ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {PURPOSE: Information on tubular carcinoma (TC) of breast is limited due to its rarity. A multi-institutional study was performed to investigate the prognosis and failure patterns of TC compared to invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: We collected retrospective data on 205 patients with TC from eleven institutions. For each TC case, 3 cases with IDC were matched according to similar size, t-stage, and n-stage from the same institution. Patterns of failure, disease free survival (DFS) and overall survival (OS) were assessed and compared between the groups.

RESULTS: DFS at 5 years was 98.8% and 97.3% and OS at 5 years was 99.5% and 99.6% in TC and IDC, respectively. Among the patients with TC, 5 patients (2.4%) developed contralateral breast cancer, while 3 patients (0.5%) presented with contralateral breast cancer in patients with IDC.

CONCLUSIONS: The TC of breast presents an excellent prognosis, but the contralateral breast cancer tends to be more frequently observed compared to IDC in Korean women.}, } @article {pmid29408073, year = {2018}, author = {Dudai, N and Tsion, I and Shamir, SZ and Nitzan, N and Chaimovitsh, D and Shachter, A and Haim, A}, title = {Agronomic and economic evaluation of Vetiver grass (Vetiveria zizanioides L.) as means for phytoremediation of diesel polluted soils in Israel.}, journal = {Journal of environmental management}, volume = {211}, number = {}, pages = {247-255}, doi = {10.1016/j.jenvman.2018.01.013}, pmid = {29408073}, issn = {1095-8630}, mesh = {*Biodegradation, Environmental ; *Chrysopogon ; Cost-Benefit Analysis ; Israel ; Soil ; Soil Pollutants ; }, abstract = {Soil pollution in Israel, due to diesel contamination, is a major concern, with gas stations, factories and refineries being the main polluters (>60%). Vetiver grass (Vetiveria zizanioides L.) is a perennial grass belonging to the Poaceae family, and is recognized world-wide for its potential as a plant with phytoremediation traits to contaminated soils. It is demonstrated here to decrease diesel contamination in field and court-yard trials. Chemical soil analysis indicated up to a 79% decrease (P < .05) in diesel pollution of contaminated soil planted with Vetiver; and at high soil contamination levels of 10 L/m[2], a significant (P < .05) reduction of 96, 96 and 87% was recorded at soil depths of 0-20, 20-40 and 40-60 cm, respectively. Furthermore, in field plots contaminated with diesel and planted with Vetiver, weeds' biomass recovered to non-polluted levels following 8 to 9 months of Vetiver treatment. An economic evaluation conducted based on the cost-benefit analysis (CBA) principles, utilizing the Net Present Value (NPV) compared phytoremediation to other currently used decontamination procedures. The economic comparison showed that phytoremediation cleanup costs are lower and more beneficial to society at large, primarily from an ecosystem services perspective. Combining the results of the agronomic examination with the economic valuation, this research pointed out that phytoremediation with Vetiver has a non-negligible potential, making it a good solution for cleansing diesel from soils on a state-wide scale in Israel and worthy of further research and development.}, } @article {pmid29403520, year = {2018}, author = {Waters, BM and Amundsen, K and Graef, G}, title = {Gene Expression Profiling of Iron Deficiency Chlorosis Sensitive and Tolerant Soybean Indicates Key Roles for Phenylpropanoids under Alkalinity Stress.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {10}, pmid = {29403520}, issn = {1664-462X}, abstract = {Alkaline soils comprise 30% of the earth and have low plant-available iron (Fe) concentration, and can cause iron deficiency chlorosis (IDC). IDC causes soybean yield losses of $260 million annually. However, it is not known whether molecular responses to IDC are equivalent to responses to low iron supply. IDC tolerant and sensitive soybean lines provide a contrast to identify specific factors associated with IDC. We used RNA-seq to compare gene expression under combinations of normal pH (5.7) or alkaline pH (7.7, imposed by 2.5 mM bicarbonate, or pH 8.2 imposed by 5 mM bicarbonate) and normal (25 μM) or low (1 μM) iron conditions from roots of these lines. Thus, we were able to treat pH and Fe supply as separate variables. We also noted differential gene expression between IDC sensitive and tolerant genotypes in each condition. Classical iron uptake genes, including ferric-chelate reductase (FCR) and ferrous transporters, were upregulated by both Fe deficiency and alkaline stress, however, their gene products did not function well at alkaline pH. In addition, genes in the phenylpropanoid synthesis pathway were upregulated in both alkaline and low Fe conditions. These genes lead to the production of fluorescent root exudate (FluRE) compounds, such as coumarins. Fluorescence of nutrient solution increased with alkaline treatment, and was higher in the IDC tolerant line. Some of these genes also localized to previously identified QTL regions associated with IDC. We hypothesize that FluRE become essential at alkaline pH where the classical iron uptake system does not function well. This work could result in new strategies to screen for IDC tolerance, and provide breeding targets to improve crop alkaline stress tolerance.}, } @article {pmid29397469, year = {2018}, author = {Yamamoto, A and Kato, M and Matsui, H and Ishida, R and Kimura, T and Funahashi, Y and Sassa, N and Matsukawa, Y and Kamihira, O and Hattori, R and Gotoh, M and Tsuzuki, T}, title = {Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.}, journal = {International journal of clinical oncology}, volume = {23}, number = {3}, pages = {584-590}, pmid = {29397469}, issn = {1437-7772}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Ductal/*drug therapy/mortality/pathology ; Docetaxel ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/*drug therapy/mortality/*pathology ; Retrospective Studies ; Taxoids/*therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).

PATIENTS AND METHODS: We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis.

RESULTS: IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively).

CONCLUSION: The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.}, } @article {pmid29397084, year = {2018}, author = {Naim-Feil, J and Rubinson, M and Freche, D and Grinshpoon, A and Peled, A and Moses, E and Levit-Binnun, N}, title = {Altered Brain Network Dynamics in Schizophrenia: A Cognitive Electroencephalography Study.}, journal = {Biological psychiatry. Cognitive neuroscience and neuroimaging}, volume = {3}, number = {1}, pages = {88-98}, doi = {10.1016/j.bpsc.2017.03.017}, pmid = {29397084}, issn = {2451-9030}, mesh = {Adult ; Attention/*physiology ; Brain/*physiopathology ; Electroencephalography ; Female ; Humans ; *Inhibition, Psychological ; Male ; Neural Pathways/physiopathology ; Neuropsychological Tests ; Schizophrenia/*physiopathology ; *Schizophrenic Psychology ; }, abstract = {BACKGROUND: Alterations in the dynamic coordination of widespread brain networks are proposed to underlie cognitive symptoms of schizophrenia. However, there is limited understanding of the temporal evolution of these networks and how they relate to cognitive impairment. The current study was designed to explore dynamic patterns of network connectivity underlying cognitive features of schizophrenia.

METHODS: In total, 21 inpatients with schizophrenia and 28 healthy control participants completed a cognitive task while electroencephalography data were simultaneously acquired. For each participant, Pearson cross-correlation was applied to electroencephalography data to construct correlation matrices that represent the static network (averaged over 1200 ms) and dynamic network (1200 ms divided into four windows of 300 ms) in response to cognitive stimuli. Global and regional network measures were extracted for comparison between groups.

RESULTS: Dynamic network analysis identified increased global efficiency; decreased clustering (globally and locally); reduced strength (weighted connectivity) around the frontal, parietal, and sensory-motor areas; and increased strength around the occipital lobes (a peripheral hub) in patients with schizophrenia. Regional network measures also correlated with clinical features of schizophrenia. Network differences were prominent 900 ms following the cognitive stimuli before returning to levels comparable to those of healthy control participants.

CONCLUSIONS: Patients with schizophrenia exhibited altered dynamic patterns of network connectivity across both global and regional measures. These network differences were time sensitive and may reflect abnormalities in the flexibility of the network that underlies aspects of cognitive function. Further research into network dynamics is critical to better understanding cognitive features of schizophrenia and identification of network biomarkers to improve diagnosis and treatment models.}, } @article {pmid29396433, year = {2018}, author = {Tvingsholm, SA and Hansen, MB and Clemmensen, KKB and Brix, DM and Rafn, B and Frankel, LB and Louhimo, R and Moreira, J and Hautaniemi, S and Gromova, I and Jäättelä, M and Kallunki, T}, title = {Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1.}, journal = {Oncogenesis}, volume = {7}, number = {2}, pages = {14}, pmid = {29396433}, issn = {2157-9024}, support = {340751/ERC_/European Research Council/International ; }, abstract = {Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. Analysis of primary breast cancer tissues reveals a gradual upregulation of MZF1 from normal breast epithelium to invasive ductal carcinoma and a negative correlation between several let-7 family members and MZF1 mRNA, suggesting that the inverse regulatory relationship between let-7 and MZF1 may play a role in the development of invasive breast cancer. Furthermore, we show that MZF1 regulates lysosome trafficking in ErbB2-positive breast cancer cells. In line with this, MZF1 depletion or let-7 expression inhibits invasion-promoting anterograde trafficking of lysosomes and invasion of ErbB2-expressing MCF7 spheres. The results presented here link MZF1 and let-7 to lysosomal processes in ErbB2-positive breast cancer cells that in non-cancerous cells have primarily been connected to the transcription factor EB. Identifying MZF1 and let-7 as regulators of lysosome distribution in invasive breast cancer cells, uncouples cancer-associated, invasion-promoting lysosomal alterations from normal lysosomal functions and thus opens up new possibilities for the therapeutic targeting of cancer lysosomes.}, } @article {pmid29395794, year = {2018}, author = {Aboulhagag, NAE and Torky, RF and Fadel, SA}, title = {Folate receptor α is associated with poor clinicopathological perspectives in breast carcinoma.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {25}, number = {1}, pages = {71-76}, doi = {10.1016/j.pathophys.2018.01.002}, pmid = {29395794}, issn = {0928-4680}, abstract = {BACKGROUND: Breast carcinoma is the commonest malignancy in females. Folate is required for the biosynthesis of nucleotide bases, amino acids, and other cellular methylation reactions in proteins and phospholipids. The high affinity folate receptor alpha (FRα) has been shown to be expressed in several kinds of human cancers.

METHODS: In this descriptive-analytic study, sections from formalin-fixed paraffin-embedded tissue blocks of 50 cases of invasive ductal breast carcinoma (IDC) as well as 15 cases of non-neoplastic breast specimens were immunohistochemically stained with FRα antibody. Histopathological evaluation for various clinicopathological parameters was done and was correlated with FRα expression.

RESULTS: Positive FRα expression was more frequently detected in IDC (64%) compared to non-neoplastic breast specimens (20%). In IDC, Positive FRα expression was significantly associated with high tumor grade (p = 0.007), large tumor size (p < 0.001), high lymph node stage (p = 0.004), presence of angiolymphatic emboli (p = 0.001), presence of perineural invasion (p = 0.001). Significant association between FRα positivity and negative hormone receptors (estrogen and progesterone) (p < 0.001) and triple negative cases (p = 0.0021).

CONCLUSION: Our work demonstrates that FRα is over expressed in IDC compared to non-neoplastic breast tissue. Folate receptor α expression was associated with poor clinicopathological perspective. This work suggests that FRα may be an independent prognostic factor and supports the possibility of using FRα-targeted therapies of breast carcinoma. However, our work requires validation on larger cohort with correlation with survival data of patients.}, } @article {pmid29394825, year = {2017}, author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Bladder Metastasis from Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1933-1935}, pmid = {29394825}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal/drug therapy/*secondary ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Urinary Bladder Neoplasms/drug therapy/*secondary ; }, abstract = {A 64-year-old woman visited hospital with a chief complaint of a nodule at the left neck skin. Skin biopsy revealed adenocarcinoma, and the diagnosis was skin metastasis of unknown primary origin. Positron emission tomography and computed tomography showed multiple bone and lymph node metastasis, left breast tumor, bladder tumor, and hydronephrosis. A needle biopsy of breast revealed invasive ductal carcinoma, and transurethral biopsy of bladder revealed adenocarcinoma. The findings were similar to those for the breast and the expression pattern of estrogen-receptor was the same. We diagnosed her with breast cancer and bladder metastasis. We administered systemic chemotherapy, however she died 10 days later. Bladder metastasis of breast cancer is rarely encountered in clinical practice and is often accompanied by life threatening symptoms. Careful histopathological examinations and rapid systemic chemotherapy are significant.}, } @article {pmid29394824, year = {2017}, author = {Goto, W and Kashiwagi, S and Asano, Y and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[A Case of Breast Cancer Associated with Dermatitis That Was Difficult to Differentiate from Dermatomyositis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1930-1932}, pmid = {29394824}, issn = {0385-0684}, mesh = {Breast Neoplasms/*complications/pathology ; Dermatitis/*diagnosis/*etiology ; Dermatomyositis/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; }, abstract = {A 46-year-old woman visited our hospital with a chief complaint of a mass in the right breast. Breast ultrasonography revealed a hypoechoic area with an indistinct border on the right breast, and right axillary lymph node swelling. A core needle biopsy revealed invasive ductal carcinoma, and the diagnosis was right breast cancer, cT2N2M0, Stage III A, HER2-enriched type. We administered 4 courses of FEC followed by weekly paclitaxel plus trastuzumab. After the treatment, she had eruption and erythema on the face, precordium and forearm. Though dermatomyositis associated cancer was suspected, a definite diagnosis was not made. However, skin symptoms were improved significantly after mastectomy, suggesting that she had dermatomyositis. For the skin symptom during breast cancer treatment, the examination should be made with the possibility of the adverse effect of chemotherapy and dermatomyositis associated cancer.}, } @article {pmid29394793, year = {2017}, author = {Katsumori, T and Ohshima, H and Hamaguchi, H and Yamamoto, S and Tsukamoto, Y and Iwanaga, T and Ohkawara, S}, title = {[A Case of Long-Term Survival of Breast Cancer with Lymph Node and Liver Metastases Treated with Sequential Anti-HER2 Drugs, Chemotherapy, and Endocrine Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1838-1840}, pmid = {29394793}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/therapy ; Chemoradiotherapy ; Endocrine System ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*antagonists & inhibitors ; }, abstract = {A 50s-year-old woman underwent left partial mastectomy with axillary lymphadenectomy for breast cancer. Histological examination indicated invasive ductal carcinoma, pT1c, pN0, Stage I , ly(+), ER(+), PgR(+). She received adjuvant therapy with tamoxifen and 50 Gy of irradiation to the residual breast. Four years after mastectomy, she was found to have left Rotter lymph node metastasis; then, anastrozole was administered instead of tamoxifen. Nine months later, she was found to have liver metastasis. Immunohistostaining revealed that the breast cancer was HER2-positive; she received AC followed by paclitaxel(PTX)with trastuzumab(T), and achieved complete response(CR). Subsequently, abdominal, cervical lymph node, and liver metastases appeared. Letrozole followed by lapatinib with capecitabine, FEC100, PTX with T, eribulin, S-1, docetaxel with pertuzumab and T, everolimus with exemestane, bevacizumab, and PTX were then administered, resulting in long-term disease control. Sixteen years after mastectomy, she receives outpatient chemotherapy in performance status 1 state.}, } @article {pmid29394791, year = {2017}, author = {Sera, T and Kashiwagi, S and Takada, K and Goto, W and Asano, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Hirakawa, K and Ohira, M}, title = {[Experience with Using the EnCor ENSPIRE®System in Mammary Tissue Biopsy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1832-1834}, pmid = {29394791}, issn = {0385-0684}, mesh = {Biopsy/*methods ; Breast Neoplasms/*pathology ; Diagnostic Errors ; Humans ; }, abstract = {We investigated the usefulness of vacuum-assisted biopsy(VAB)using the EnCor ENSPIRE®system for initial biopsy of breast tumors. We analyzed 24 cases of VAB using the EnCor ENSPIRE®system performed for breast tumors. Of 24 mammary lesions, 12 cases(50.0%)were diagnosed as malignant. Among them, 7 cases(29.2%)were invasive ductal carcinoma(IDC) and 5 cases(20.8%)were ductal carcinoma in situ(DCIS). Six cases required tumor resection for definitive diagnosis; 1 case was diagnosed with IDC, 2 cases with DCIS, 2 cases with intraductal papilloma(IDP), and 1 case with atypical ductal hyperplasia(ADH). Moreover, EnCor ENSPIRE®system biopsy was performed in 15 cases because malignancy could not be diagnosed using core needle biopsy. There were 4 cases of IDC, 4 cases of DCIS, 2 cases of IDP, 2 cases of usual ductal hyperplasia, and 2 cases of ADH. There were no complications due to a series of procedures. We believe that the EnCor ENSPIRE®system is an effective technique having both convenience and great diagnostic accuracy.}, } @article {pmid29394726, year = {2017}, author = {Adachi, K and Sakurai, K and Suzuki, S and Kubota, H and Hara, Y and Abe, K and Fujiwara, A and Hirano, T and Enomoto, K and Masuda, S and Makishima, M and Koshinaga, T}, title = {[Breast Cancer Occurring in the Axillary Area - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1635-1637}, pmid = {29394726}, issn = {0385-0684}, mesh = {Antineoplastic Agents/therapeutic use ; Axilla ; Biopsy ; Breast Neoplasms/drug therapy/*pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/surgery ; Female ; Humans ; Middle Aged ; }, abstract = {A 50-year-old woman aware a lump in the right axillary area 5 years ago.She noticed that the lump gradually became bigger, accompanied by redness and gathering of the skin; therefore, she consulted a dermatologist.On receiving the result of skin biopsy, she was referred for a suspected metastatic lesion from breast cancer.The mass was 20mm in diameter, was palpable in the right axillary area, and accompanied by redness of the skin.Ultrasonography revealed 2 irregular-shaped masses in the right axillary area.An FDG/PET study showed some abnormal uptake in the right axillary area, but there were no other primary lesions in any other organs.We performed tumorectomy, and the axillary tumors was histopathologically diagnosed as invasive ductal carcinoma.This case was comprehensively presumed to be accessory breast cancer.In the case of malignant tumor in the axillary area, differential diagnoses are axillary lymph node metastasis of latent breast cancer, ectopic breast cancer, accessory breast cancer, and malignant tumors of skin and its appendages.We presented here a case of carcinoma that was estimated as accessory breast cancer considering clinical, radiological and pathological findings in an integrating manner.}, } @article {pmid29394714, year = {2017}, author = {Lee, T and Kawajiri, H and Nakata, B and Masuda, G and Tendo, M and Hori, T and Ohsawa, M and Ishikawa, T}, title = {[A Case of Paget-Type Recurrence 20 Years after Breast Conserving Surgery for Invasive Ductal Carcinoma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1598-1600}, pmid = {29394714}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; Mastectomy, Segmental ; Paget's Disease, Mammary/pathology/*surgery ; Recurrence ; Time Factors ; }, abstract = {We report an 85-year-old female suffered Paget-type recurrence at right remnant breast. The patient had undergone breast conserving surgery(BCS)20 years ago in another hospital for invasive ductal carcinoma of the right breast(pT1N0M0, Stage I). Her chief complain was a skin ulcer of the right nipple. The pathological diagnosis for biopsy specimen from the areola was Paget's disease. She underwent total mastectomy. Paget cells were detected pathologically in the epidermis of the nipple and nearby mammary duct connected with fibrous tissue after BCS, suggesting Paget-type recurrence of invasive breast carcinoma.}, } @article {pmid29394713, year = {2017}, author = {Waraya, M and Hayashi, K and Oshida, S and Yamamoto, K and Hosoya, S and Habiro, T and Inukai, M and Kosaka, Y and Sengoku, N and Watanabe, M}, title = {[A Case Report of Ipsilateral Nipple Skin Recurrence].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1595-1597}, pmid = {29394713}, issn = {0385-0684}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*secondary/*surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Nipples/*pathology/surgery ; Recurrence ; }, abstract = {We report our experience with a patient with breast cancer who showed recurrence in the nipple skin 5 years and 10 months after a breast-preserving surgery. The patient was a woman, and was 65-years old at the time of initial surgery. Breast-preserving surgery and axillary lymph-node dissection were performed for left breast cancer. Invasive ductal carcinoma of the breast(pT3N0M0)was triple-negative, and the patient postoperatively received adjuvant chemotherapy. Left breast pain developed 5 years and 6 months after surgery. Computed tomography showed no evidence of recurrence, and the symptoms resolved after treatment with non-steroidal anti-inflammatory drugs(NSAIDs). After 3 months, however, the left nipple had enlarged to about 1.5 cm, and the surrounding skin was red and painful. Treatment with NSAIDs was thus resumed. After 1 week, redness of the nipple skin and pain were improved. However, the nipple had enlarged to twice its normal size. Nipple skin biopsy was subsequently performed, and revealed adenocarcinoma invading the skin. Left axillary lymph-node metastasis was suspected, but there was no evidence of metastasis to other sites or recurrence. Conservative total mastectomy with axillary lymph-node dissection was thus performed. The histopathological diagnosis was the recurrence of invasive ductal carcinoma, arising mainly in the reticular layer of the dermis. Chemotherapy was administered postoperatively. There has been no evidence of recurrence as of 1 year after surgery.}, } @article {pmid29394684, year = {2017}, author = {Takeda, Y and Murata, K and Ohmura, Y and Katsura, Y and Sakamoto, T and Nose, Y and Mori, R and Kawai, K and Inatome, J and Murakami, K and Naito, A and Kagawa, Y and Masuzawa, T and Takeno, A and Egawa, C}, title = {[Laparoscopic Pancreatectomy for Pancreatic Neuroendocrine Tumor - A Single Institution Experience].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1509-1511}, pmid = {29394684}, issn = {0385-0684}, mesh = {Aged ; Female ; Humans ; Laparoscopy ; Male ; Neoplasm Invasiveness ; Neuroendocrine Tumors/*surgery ; *Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; }, abstract = {BACKGROUND: Pancreatic neuroendocrine tumor(P-NET)is relatively rare and often has less aggressive biological behavior. P-NET was re-designated by the WHO in 2010 and 2017. Laparoscopic surgery is minimally invasive but has technical difficulties such as limitation of movement and laparoscopic view. The purpose of this study is to evaluate the efficacy of laparoscopic pancreatectomy(LPT)for P-NET.

METHODS: Between January 2012 and June 2017, 6 patients underwent LPT for P-NET at Kansai Rosai Hospital. Five patients who received open pancreatectomy(OPT)for P-NET and 41 patients who received laparoscopic distal pancreatectomy(LDP)for cystic tumor(CyT)or invasive ductal carcinoma(IDC)were included for comparison.

RESULTS: All patients who underwent LPT for P-NET were NET G1 in WHO Classification 2017 and Stage I in UICC TNM 2016. No significant differences were noted between LPT and OPT groups with respect to patient age or gender. Operation time was 421.5 versus 423.5 minutes(ns), blood loss was 121.7 versus 1,918.3mL(ns), hospital stay was 20.5 versus 58.0 days(ns)for LPT and OPT respectively. In LDP, there were no significant differences between PNEN, CyT, and IDC groups with respect to patient age, gender, operation time, blood loss and hospital stay. All patients who underwent LPT for P-NET alive without recurrence. The average observation period was 58.4 months.

CONCLUSIONS: Laparoscopic pancreatectomy is safe and effective approach to the management of pancreatic neuroendocrine neoplasm.}, } @article {pmid29394575, year = {2017}, author = {Noda, M and Tachibana, K and Nakano, H and Abe, S and Murakami, Y and Okano, M and Abe, N and Yoshida, S and Kiko, Y and Hashimoto, Y and Ohtake, T}, title = {[A Case of Breast Carcinoma Associated with Osteoclast-Like Giant Cells].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1185-1187}, pmid = {29394575}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Giant Cells/*pathology ; Humans ; Osteoclasts/*pathology ; Sentinel Lymph Node Biopsy ; }, abstract = {Mammary carcinoma with osteoclast-like giant cells is uncommon, and its onset mechanism and malignancy are unknown. We report a case of mammary carcinoma with osteoclast-like giant cells. A 41-year-old woman noticed a lump in her left breast. Ultrasound sonography findings suggested breast cancer. A core needle biopsy revealed invasive ductal carcinoma of the breast. Modified radicalmastectomy and sentinell ymph node biopsy were performed. Histopathologicalexamination revealed papillotubular carcinoma with osteoclast-like giant cells. Cells were positive for estrogen receptor and progesterone, and negative for HER2. MIB-1 index was under 5%. The giant cells were generally associated with an inflammatory, fibroblastic, hyper-vascular stroma. The carcinomatous part of the lesion was most frequently a well-to moderately differentiated invasive ductalcarcinoma. Immunohistochemicaland ultrastructuralstudies suggested that the osteoclast-like giant cells were of stromalhistiocytic origin. To understand biochemicalfindings of this carcinoma, more case studies are required to be reported.}, } @article {pmid29394548, year = {2017}, author = {Ikarashi, M and Nagahashi, M and Endo, M and Otani, A and Tsuchida, J and Moro, K and Niwano, T and Yamaura, K and Toshikawa, C and Hasegawa, M and Nakajima, M and Sakata, J and Kobayashi, T and Kameyama, H and Wakai, T}, title = {[Clinical Experience of a Primary Accessory Breast Cancer Patient].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1104-1106}, pmid = {29394548}, issn = {0385-0684}, mesh = {Axilla ; Biopsy ; Breast Neoplasms/*pathology/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {A 59-year-old woman attended a previous hospital complaining of a nodule of the right axilla. Although ultrasonography had shown no evidenceof malignancy, a growth of thenodulewas found on follow-up. Excisional biopsy revealed a primary accessory breast cancer. Because the resected margins were involved, she was referred to our hospital for additional treatment. Based on imaging, both bilateral mammary glands and axillary lymph nodes were reported normal, and distant metastasis was not observed. We performed additional resection of the right axillary tissue around the biopsy site and the right axillary lymph nodedisse ction. Histo-pathological examination revealed the residual invasive ductal carcinoma in the resected specimen. Both the new surgical margins and the lymph nodes were free of disease. Accessory breast cancer is relatively rare, with the incidence being less than 1% of all breast cancers. It is most frequent in the axillary region. Local extensive resection with sufficient surgical margin and axillary lymph node dissection are generally required. This case report presents our clinical experience of accessory breast cancer with some discussion of the literature.}, } @article {pmid29394543, year = {2017}, author = {Fukui, Y and Kashiwagi, S and Takada, K and Goto, W and Asano, Y and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Ohsawa, M and Hirakawa, K and Ohira, M}, title = {[A Case of Ductal Carcinoma In Situ in Sclerosing Adenosis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1089-1091}, pmid = {29394543}, issn = {0385-0684}, mesh = {Aged ; Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/surgery ; *Carcinoma in Situ/surgery ; Female ; Fibrocystic Breast Disease/*pathology/surgery ; Humans ; Treatment Outcome ; }, abstract = {A 67-year-old female was referred to our hospital because she was pointed out mass in her right breast by her previous doctor. Core needle biopsy examination was performed at that time which revealed invasive ductal carcinoma. There'reno palpable masses in her breast or any superficial lymph nodes on her visiting our hospital. Breast ultrasonography images showed multiple nodules in C area of right breast. Breast enhanced MRI image revealed multiple enhanced nodules which showed rapid arising and plateau or slowly decreasing pattern in time intensity curve. CT scan and bone scintigraphy revealed no distant metastasis. Based on these findings, the case was diagnosed as right breast cancer, cT1N0M0, Stage I . For this case, we performed right mastectomy and sentinel lymph node biopsy. The pathological findings was ductal carcinoma in situ (DCIS)accompanied by sclerosing adenosis. Though we didn't perform adjuvant chemotherapy, she has been alive without recurrence for 6 years. Because it's difficult to make correct diagnosis with small specimen collected by core needle biopsy, we should take DCIS in sclerosing adenosis into consideration to prevent overdiagnosis.}, } @article {pmid29394542, year = {2017}, author = {Yamamoto, T and Tokunou, K and Kamei, R and Yamamoto, H and Tokuhisa, A and Kitamura, Y and Ando, S}, title = {[Three Cases of Remnant Pancreatic Cancer after Surgery for Invasive Ductal Carcinoma of Pancreas].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1086-1088}, pmid = {29394542}, issn = {0385-0684}, mesh = {Aged ; *Carcinoma, Pancreatic Ductal/surgery ; Female ; Humans ; Male ; Pancreatectomy ; Pancreatic Neoplasms/*pathology/surgery ; Pancreaticoduodenectomy ; Treatment Outcome ; }, abstract = {We report here 3 cases of remnant pancreatic cancer after surgery for invasive ductal carcinoma. Case 1 was a 73-year-old male who underwent distal pancreatectomy(pap, pT3, pN0, M0): fStage II A(JPS 7th). He developed a remnant pancreatic cancer 39 months later, and total remnant pancreatectomy was performed. He died from sepsis 9 months after surgery. Case 2 was a 72-year-old female who underwent subtotal stomach-preserving pancreatoduodenectomy(SSPPD)(tub2, pT1c, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 82 months later. This lesion seemed to be resectable. But she hoped to take a best supportive care, and died 13 months after diagnosis. Case 3 was a 68-year-old female who underwent SSPPD(tub1, pT3, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 20 months later and was successfully treated by chemotherapy and carbon-ion radiotherapy.}, } @article {pmid29394534, year = {2017}, author = {Inoue, T and Shimomura, A and Sugimoto, T and Wakamiya, S and Chou, U and Fujiwara, A and Uchikoshi, F and Watanabe, T and Kitamura, N}, title = {[Local Control of Advanced Breast Cancer with Giant Ulcer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1062-1064}, pmid = {29394534}, issn = {0385-0684}, mesh = {Biopsy ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal/complications/*therapy ; Chemoradiotherapy ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Ulcer/*etiology ; }, abstract = {This study reports the treatment and local control of advanced breast cancer with a giant ulcer. A 53-year-old woman presented with a large left breast tumor and an associated giant ulcer, with massive exudates, bleeding, and an offensive odor. Histopathological examination revealed an invasive ductal carcinoma(Luminal B type). Computed tomography(CT) showed multiple metastases to the lymph nodes, lungs, liver and bones. The patient received chemotherapy with a combina- tion of paclitaxel(PTX 90mg/m / 2)and bevacizumab(BEV 10 mg/kg). After 4 courses of chemotherapy, there was a significant reduction in the tumor size, the discharge of exudates and bleeding as well as lumbago and femoral pain. High CEA and CA15-3 levels had been normalized and CT showed a remarkable decrease in metastases. Compared to the tumor itself, the ulcer associated with it had shown a smaller decrease in size, and there was the possibility of perforation in the thin chest wall. Suspecting these outcomes to the adverse events of BEV, its use was discontinued, and starting with course 5 of chemothera- py, we administrated only PTX(90mg/m2). Subsequently, the ulcer showed obvious granulation and was infected. CT of the chest prior to the second course of PTX revealed pleurisy, pneumonia and atelectasis. Following the administration of antibiotics, while infection in the ulcer had subsided, pleurisy and pneumonia continued, with increased right pleural effusion, which finally required drainage. We had to discontinue the administration of PTX. BEV, although effective as first-line therapy, has the adverse effect of slowing wound healing. Therefore, even though the combination therapy of BEV and PTX is markedly effective for systemic therapy, it should be altered for local wound healing as in this case.}, } @article {pmid29394533, year = {2017}, author = {Tsujio, G and Kashiwagi, S and Asano, Y and Goto, W and Takada, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Ohsawa, M and Hirakawa, K and Ohira, M}, title = {[A Case of T1a Breast Cancer with Axillary Lymph Node Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {44}, number = {12}, pages = {1059-1061}, pmid = {29394533}, issn = {0385-0684}, mesh = {Axilla ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Chemoradiotherapy ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Treatment Outcome ; }, abstract = {A breast cancer with tumors smaller than or equal to 5mm in diameter is treated as a microscopic lesion and axially lymph node metastasis is considered to be rare. A 52-year-old female was found to have an abnormal shadow on mammography. An ultrasonography revealed a poorly defined and irregular shaped mass with calcification, 4mm in diameter, in the AC area of her left breast. We performed vacuum-assisted biopsy and diagnosed with invasive ductal carcinoma. Under a preoperative diagnosis of left breast cancer with cT1aN0M0, stage I , Luminal A like, we underwent partial mastectomy with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed level II axillary lymph node dissection. The size of the tumor was 4mm and diagnosed with pT1a breast cancer. Histopathological diagnosis was papillotubular carcinoma. Radiotherapy was performed(total: 50 Gy)followed by endocrine therapy (tamoxifen). She is alive without recurrence and metastasis 5 years after surgery.}, } @article {pmid29394219, year = {2018}, author = {Kim, HJ and Kim, SY and Huh, S}, title = {Multimodality Imaging Findings of Metaplastic Breast Carcinomas: A Report of Five Cases.}, journal = {Ultrasound quarterly}, volume = {34}, number = {2}, pages = {88-93}, pmid = {29394219}, issn = {1536-0253}, mesh = {Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Adenosquamous/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Multimodal Imaging/methods ; Positron Emission Tomography Computed Tomography/*methods ; Reproducibility of Results ; Ultrasonography, Mammary ; }, abstract = {Metaplastic carcinoma is a rare subtype of breast cancer that comprises histologically diverse malignancies. Metaplastic carcinoma tends to have an aggressive clinical presentation, high metastatic potential, and more chances of local recurrence, as compared with intraductal carcinoma. Although many clinical and pathologic finding have been reported, to our knowledge, there are few reports of imaging findings for this type of tumor.In this study, we reviewed data of 5 patients with histopathologically proven metaplastic breast carcinoma. Multimodality imaging findings including those from mammography, ultrasonography, magnetic resonance imaging, and positron emission tomography-computed tomography were recorded.The results indicated that metaplastic carcinomas tend to show more benign imaging features such as round or oval shape with circumscribed margins and less axillary lymph node metastasis compared with invasive ductal carcinoma. High signal intensity on T2-weighted magnetic resonance imaging due to its cystic or necrotic component may be useful for diagnosis of metaplastic carcinoma.}, } @article {pmid29392646, year = {2018}, author = {Sakamoto, U and Fukuba, N and Ishihara, S and Sumi, S and Okada, M and Sonoyama, H and Ohshima, N and Moriyama, I and Kawashima, K and Kinoshita, Y}, title = {Postoperative recurrence from tract seeding after use of EUS-FNA for preoperative diagnosis of cancer in pancreatic tail.}, journal = {Clinical journal of gastroenterology}, volume = {11}, number = {3}, pages = {200-205}, pmid = {29392646}, issn = {1865-7265}, mesh = {Carcinoma, Pancreatic Ductal/*diagnostic imaging/pathology/*surgery ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/*adverse effects/instrumentation ; Endoscopy, Digestive System ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Neoplasm Seeding ; Pancreatectomy ; Pancreatic Neoplasms/*diagnostic imaging/pathology/*surgery ; Postoperative Complications/*diagnosis/pathology ; Recurrence ; Stomach Neoplasms/*diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {A 50-year-old male underwent abdominal computed tomography at a city hospital in Japan, which revealed a tumor 38 mm in diameter in the tail of the pancreas. Based on findings from endoscopic ultrasonography-guided fine needle aspiration using a 22-gauge needle with a side hole, the tumor was diagnosed as an invasive ductal carcinoma. The patient was referred to our hospital and underwent a distal pancreatectomy. Esophagogastroduodenoscopy performed as part of a medical checkup at another hospital 2 years later revealed a 20-mm-sized submucosal tumor in the posterior wall of the upper body of the stomach. Examination of a biopsy specimen obtained from the top of the lesion revealed adenocarcinoma. Partial resection of the stomach was performed and pathological findings showed an adenocarcinoma in all layers of the stomach wall, consistent with recurrence derived from needle tract seeding of the previously excised cancerous tumor from the pancreatic tail. Additional experimentation performed for confirmation with an agar model showed that agar on the deep side leaked to the shallow side following puncture with a needle with a side hole used with a slow-pull technique.}, } @article {pmid29388117, year = {2018}, author = {Wang, Y and Wang, J and Long, F and Wang, N and Zhang, B and Han, H and Wang, Y}, title = {Correlation of FANCM expression with clinical factors in luminal B breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {25}, number = {4}, pages = {431-437}, doi = {10.1007/s12282-018-0841-0}, pmid = {29388117}, issn = {1880-4233}, support = {81572591//National Natural Science Foundation of China/ ; }, mesh = {Asian People ; Breast Neoplasms/*metabolism/mortality/*pathology ; DNA Helicases/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/metabolism/mortality/pathology ; }, abstract = {BACKGROUND: The genotype of Fanconi Anemia complementation group M (FANCM) was previously found to be associated with breast cancer risk in several populations. Here, we studied the expression of FANCM and its correlation with clinical characteristics in Chinese patients with breast cancer.

METHODS: We performed an immunohistochemical study of FANCM protein in clinical breast cancer tissues from 310 patients along with 44 adjacent tissues.

RESULTS: FANCM protein level is lower in triple-negative breast cancer tissues than in other subtypes (P = 0.008). In addition, high FANCM expression correlated with pathology type IDC (P = 0.040), estrogen receptor positive (P < 0.001), progesterone receptor positive (P = 0.001), and low Ki-67 status (P = 0.003). Multivariate analysis revealed that FANCM status was an independent prognostic factor for overall survival (P = 0.017) in luminal B breast cancer.

CONCLUSIONS: FANCM levels are significantly associated with different subtypes of human breast cancer. Specifically, FANCM could play a role in the progression of luminal B breast cancer.}, } @article {pmid29387559, year = {2017}, author = {Luo, R and Lee, SL and Ng, FC and Koh, LT}, title = {Inadvertent placement of a urinary catheter into the ureter: A report of 3 cases and review of the literature.}, journal = {Asian journal of urology}, volume = {4}, number = {4}, pages = {256-261}, pmid = {29387559}, issn = {2214-3882}, abstract = {We describe three cases of inadvertent placement of the urinary catheter into the ureter. An 85-year-old gentleman on long-term indwelling catheter (IDC) for neurogenic bladder presented with fever and right flank pain. CT of abdomen and pelvis demonstrated the tip of the IDC to be located within the right vesicoureteric junction with acute right hydronephrosis and acute pyelonephritis. A 74-year-old woman, on long-term IDC for neurogenic bladder was found to have hydronephrosis on ultrasound imaging. Contrast-enhanced CT intravenous pyelography done subsequently showed the IDC was in the right distal ureter. A 47-year-old lady, on IDC for urinary retention and voiding dysfunction likely secondary to schizophrenia and anti-psychotic medications, presented with raised creatinine. A non-enhanced CT of her abdomen and pelvis was done and showed that the tip of the urethral IDC was located up to the left vesicoureteric junction. In all patients, the hydronephrosis resolved after changing the catheter and they were well on discharge. We also review the literature to identify the incidence, outcomes and possible risk factors. To our knowledge, only 20 cases have been reported thus far in the English literature. Although serious complications can occur, the incidence is very low. One risk factor that has been identified is long-term catheterization in patients with neurogenic bladder. We do not recommend routine imaging after catheterization in this group of patients. However, we should still be mindful of the possibility of this occurrence and evaluate and treat as necessary when clinical suspicion arises.}, } @article {pmid29379128, year = {2018}, author = {Tortarolo, M and Lacoste, B and Hem, J and Dieudonné, C and Cyrille, MC and Katine, JA and Mauri, D and Zeltser, A and Buda-Prejbeanu, LD and Ebels, U}, title = {Injection locking at 2f of spin torque oscillators under influence of thermal noise.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {1728}, pmid = {29379128}, issn = {2045-2322}, abstract = {Integration of Spin Torque Nano-Oscillators STNO's in conventional microwave circuits means that the devices have to meet certain specifications. One of the most important criteria is the phase noise, being the key parameter to evaluate the performance and define possible applications. Phase locking several oscillators together has been suggested as a possible means to decrease phase noise and consequently, the linewidth. In this work we present experiments, numerical simulations and an analytic model to describe the effects of thermal noise in the injection locking of a tunnel junction based STNO. The analytics show the relation of the intrinsic parameters of the STNO with the phase noise level, opening the path to tailor the spectral characteristics by the magnetic configuration. Experiments and simulations demonstrate that in the in-plane magnetized structure, while the frequency is locked, much higher reference currents are needed to reduce the noise by phase locking. Moreover, our analysis shows that it is possible to control the phase noise by the reference microwave current (IRF) and that it can be further reduced by increasing the bias current (IDC) of the oscillator, keeping the reference current in feasible limits for applications.}, } @article {pmid29378343, year = {2018}, author = {Enríquez-Marulanda, A and Beltrán-Osorio, LD and Escobar, LA and Granados, AM and Velásquez-Lasprilla, F and Orozco, JL}, title = {Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute Cerebellitis with Posterior Cranial Fossa Hypertension.}, journal = {World neurosurgery}, volume = {112}, number = {}, pages = {117-122}, doi = {10.1016/j.wneu.2018.01.105}, pmid = {29378343}, issn = {1878-8769}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Cranial Fossa, Posterior/*pathology/surgery ; Craniotomy/*methods ; Female ; Humans ; Intracranial Hypertension/*etiology/pathology/surgery ; Middle Aged ; Paraneoplastic Cerebellar Degeneration/*complications/pathology/surgery ; }, abstract = {BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication of some malignant cancers. It is most commonly described in women with gynecologic or breast malignancies; however, there have been reports in other types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could be the first manifestations of an underlying malignancy.

CASE DESCRIPTION: A 50-year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast invasive ductal carcinoma. She presented with intracranial hypertension in the posterior cranial fossa that required an emergent decompressive craniectomy.

CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse cerebellar swelling. To our knowledge, this is the first described case of an anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension owing to diffuse cerebellar edema. Early diagnosis and treatment should be pursued to improve long-term outcomes.}, } @article {pmid29373327, year = {2018}, author = {D'heygere, E and Meulemans, J and Vander Poorten, V}, title = {Salivary duct carcinoma.}, journal = {Current opinion in otolaryngology & head and neck surgery}, volume = {26}, number = {2}, pages = {142-151}, doi = {10.1097/MOO.0000000000000436}, pmid = {29373327}, issn = {1531-6998}, mesh = {Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Rare Diseases ; Receptor, ErbB-2/genetics ; Receptors, Androgen/genetics ; Risk Assessment ; Salivary Ducts/*pathology/surgery ; Salivary Gland Neoplasms/*genetics/mortality/pathology/*surgery ; Survival Rate ; }, abstract = {PURPOSE OF REVIEW: The review puts new information on geno- and phenotype of salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO classification.

RECENT FINDINGS: The proportion of SDC is increasing. This may be because of a true rise in incidence, but certainly to better diagnostic tests and changed WHO definitions. In this light, a substantial proportion of carcinoma expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC' and 'SDC in-situ' of the former WHO classification, are now named low-grade and high-grade intraductal carcinoma (IDC), respectively. Recent series quantify biologic aggressiveness: perineural growth, vascular invasion, and extracapsular extension in lymph node metastasis are each observed in two out of three patients with SDC. Most patients die within 3 years, but once 5-year disease-free survival is reached, further disease activity is exceptional. The typical molecular biological profile with high human epidermal growth factor receptor 2 and androgen receptor expression is increasingly successfully exploited in clinical trials for advanced SDC.

SUMMARY: The aggressive SDC is increasingly diagnosed. Despite intensive combined surgery and radiation therapy, many patients recur, for whom new bullets, targeting the molecular biological mechanisms, are the subject of ongoing clinical trials.}, } @article {pmid29373286, year = {2018}, author = {Sachdeva, R and Schlotterer, A and Schumacher, D and Matka, C and Mathar, I and Dietrich, N and Medert, R and Kriebs, U and Lin, J and Nawroth, P and Birnbaumer, L and Fleming, T and Hammes, HP and Freichel, M}, title = {TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation.}, journal = {Molecular metabolism}, volume = {9}, number = {}, pages = {156-167}, pmid = {29373286}, issn = {2212-8778}, mesh = {Animals ; Cells, Cultured ; Diabetic Retinopathy/genetics/*metabolism ; Female ; Lactoylglutathione Lyase/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pyruvaldehyde/blood/*metabolism ; Retina/metabolism ; TRPC Cation Channels/*genetics/metabolism ; }, abstract = {OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6[-/-] compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy.

METHODS: We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6[-/-] cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay.

RESULTS: We find that Trpc1/4/5/6[-/-] mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6[-/-] mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6[-/-] mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6[-/-] mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina.

CONCLUSION: The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6[-/-] mice is suggestive of a predominant action of TRPCs in Müller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit.}, } @article {pmid29367511, year = {2017}, author = {Sakamoto, N and Ueda, S and Mizoguchi, H and Kawahara, I and Kobayashi, T and Hamaguchi, M and Yoshikawa, M}, title = {[SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE BIOCHEMICAL RECURRENCE].}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {108}, number = {1}, pages = {5-11}, doi = {10.5980/jpnjurol.108.5}, pmid = {29367511}, issn = {0021-5287}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/*etiology ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/pathology/*surgery ; Time Factors ; }, abstract = {(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and total cancer volume (p<0.0001) were significantly associated with the biochemical progression-free survival. In a multivariate analysis, Gleason score (p<0.0001), IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were significantly associated with biochemical progression-free survival. (Conclusions) The presence of IDC-P is an independent factor of biochemical recurrence in prostate cancer patients treated with radical prostatectomy. We therefore recommend that the presence of IDC-P in radical prostatectomy specimens be reported.}, } @article {pmid29362505, year = {2018}, author = {Hand, BN and Krause, JS and Simpson, KN}, title = {Polypharmacy and adverse drug events among propensity score matched privately insured persons with and without spinal cord injury.}, journal = {Spinal cord}, volume = {56}, number = {6}, pages = {591-597}, pmid = {29362505}, issn = {1476-5624}, support = {UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Female ; Humans ; Insurance, Health ; Likelihood Functions ; Male ; Middle Aged ; Odds Ratio ; *Polypharmacy ; Propensity Score ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Spinal Cord Injuries/drug therapy/*epidemiology ; United States/epidemiology ; Young Adult ; }, abstract = {STUDY DESIGN: Retrospective quasi-experimental design.

OBJECTIVES: To compare the incidence of adverse drug events (ADEs) between persons with and without spinal cord injury (SCI), while controlling for all potential and available risk factors.

SETTING: A commercially available claims dataset consisting of ~170 million patient cases in the United States between 2012 and 2013.

METHODS: Participants (aged 18-64 years) included 2779 persons with polypharmacy and traumatic or non-traumatic SCI and 2779 propensity score-matched persons with polypharmacy without SCI. The cohorts were matched using demographic variables including number of concomitant prescriptions, comorbidities, hospital admissions, age, gender, and geographic region. Inpatient and outpatient claims records containing 395 distinct IDC-9 codes indicative of ADEs were extracted. Incidence and frequency of ADEs were compared between groups using logistic and Poisson regression, respectively.

RESULTS: Persons with SCI were significantly more likely to experience an ADE than matched controls (Odds Ratio = 1.45, p < 0.0001). Among persons with ADEs (n = 1552), individuals with SCI experienced fewer ADEs over time than matched controls (Incidence Rate Ratio = 0.91, p < 0.0001).

CONCLUSIONS: While persons with SCI and polypharmacy are at a greater risk for experiencing an ADE, their medical care after an ADE may be better managed than that of a matched control population. There may be a need for practice guidelines that facilitate proactive identification of persons with SCI at the highest risk of ADE. Steps may then be taken to mitigate risk, in contrast to current practice trends that appear to take a reactive approach after an ADE has occurred.}, } @article {pmid29362351, year = {2018}, author = {Sakagami, M and Hirano, T and Suzuki, S and Adachi, K and Kubota, H and Hara, Y and Enomoto, K and Tomita, R and Fujisaki, S and Sakurai, K}, title = {[A Case of Advanced Breast Cancer with Liver Metastasis Successfully Treated with Multi-Disciplinary].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {1}, pages = {190-192}, pmid = {29362351}, issn = {0385-0684}, mesh = {Adult ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal/*drug therapy/*secondary/surgery ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/*secondary ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {We report a case of advanced breast cancer with liver metastasis(T2N1M1, Stage IV)achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was 37-year-old woman who had breast lump and axillary lymph nodes swelling with liver metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, negative for estrogen receptor and progesterone receptor, and positive for HER2/neu protein expression. The Ki-67 positive cell index was 40%. She received 16 courses of DOC plus HER plus PER(docetaxel 75mg/m / 2, trastuzumab 6 mg/kg, pertu- zumab 450mg/body, and received 4 courses of EC(epirubicin 90mg/m / 2, cyclophosphamide 600 mg/m2). The breast lesion and liver metastatic lesion disappeared after chemotherapy. We checked up whole body. There was no metastatic lesion. Therefore, we diagnosed a clinical complete response. We performed muscle preserving mastectomy and axillary lymph nodes dissection. The pathological diagnosis from resected specimens were pathological complete response. The surgical margin was negative. She was started the endocrine therapy by tamoxifen(20mg/day). Three years after surgery, she was well without metastases. Multi-disciplinary therapy can improve patient QOL and the clinical outcomes in Stage IV advanced breast cancer.}, } @article {pmid29362339, year = {2018}, author = {Egawa, C and Inatome, J and Sakamoto, T and Naito, A and Murakami, K and Katsura, Y and Ohmura, Y and Kagawa, Y and Takeno, A and Takeda, Y and Murata, K and Takatsuka, Y and Goto, T and Nagano, T}, title = {[A Case of Stage IV Metaplastic Breast Cancer in Which Primary Tumor Was Removed after Treatment with Anti-HER2 Systemic Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {1}, pages = {154-156}, pmid = {29362339}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/*pathology/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {The patient was a 58-year-oldpostmenopausal woman. Vacuum assistedbiopsy of the left breast tumor revealedinvasive ductal carcinoma. Immunohistochemical examination was negative for estrogen receptor(ER), negative for progesterone receptor(PgR), andshowedan HER2 score of 3+. FDG-PET/CT revealedmultiple metastases to the left supracravicular and axillary lymph nodes and lungs. She was diagnosed with HER2-positive T3N3M1, Stage IV breast cancer. A 2-year regimen of chemotherapy with trastuzumab andvinorelbine achieveda complete response with regardto the metastatic sites; however, the size of the primary tumor increasedd espite the chemotherapy, andsurgical resection of the left breast with axillary lymph node dissection was performed for local control. Pathological examination of the surgical specimen revealed metaplastic carcinoma with sarcoma component surrounded by non-invasive ductal carcinoma. No component of invasive ductal carcinoma was found. Immunohistochemically, metaplastic carcinoma was negative for ER, negative for PgR, andrevealedan HER2 score of 0. There was discordance of HER2 status between pre- andpost -chemotherapy. The patient receivedno further chemotherapy following surgery andhas been without disease progression for 6 years. We suggest there is heterogeneity, that is, the metastatic sites andthe partial primary tumor were HER2-positive invasive ductal carcinoma and the remainder of the primary tumor was triple negative metaplastic carcinoma. As a result, the patient was able to discontinue chemotherapy with higher quality of life.}, } @article {pmid29362334, year = {2018}, author = {Kinoshita, H and Teraoka, H and Maekawa, Y and Kitano, M and Morikawa, M and Sugita, Y and Sakamoto, A and Uono, H and Mori, T and Kuroda, K and Nanbara, M and Noda, E and Kashiwagi, S and Hirakawa, K and Ohira, M}, title = {[Usefulness of Vacuum-Assisted Biopsy(VAB)at Initial Biopsy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {1}, pages = {139-141}, pmid = {29362334}, issn = {0385-0684}, mesh = {*Biopsy, Needle ; Breast Neoplasms/diagnosis/*pathology ; Humans ; Vacuum ; }, abstract = {In recent years, breast micro-lesions such as ductal carcinoma in situ(DCIS)were detected with progress of the image diagnosis. We investigated the usefulness of vacuum-assisted biopsy(VAB)for initial biopsy of breast tumors. We analyzed 32 cases of VAB performed for breast tumors. The pathological diagnosis of the biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and benign lesions in 21 cases. 11 cases underwent surgery and the final histopathological diagnosis was the same in 10 of them. One case histopathology varied from DCIS to invasive ductal carcinoma(IDC). It was suggested that VAB at initial biopsy was a useful biopsy method.}, } @article {pmid29362313, year = {2018}, author = {Sakurai, K and Fujisaki, S and Kubota, H and Hara, Y and Suzuki, S and Adachi, K and Tomita, R and Enomoto, K and Hirano, T}, title = {[Long-Term Effect of Fulvestrant for Locally Advanced Breast Cancer in an Elderly Patient - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {1}, pages = {76-78}, pmid = {29362313}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Estradiol/*analogs & derivatives/therapeutic use ; Female ; Fulvestrant ; Humans ; Time Factors ; }, abstract = {We report an elderly patient with locally advanced breast cancer who received long-term fulvestrant therapy.The patient was a 75-year-old woman who presented with a right breast lump.She noticed the tumor 4 years and 6 months ago, but she had not visited any hospital.However, her daughter brought her to our hospital.The tumor was 73mm in diameter.A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), and negative for HER2/neu.The Ki-67 positive cell index was 20%.We performed a whole- body checkup, and confirmed the diagnosis as T4cN1M0, Stage III B.She initiated endocrine therapy by letrozole(2.5 mg/ day).After 1 year and 6months, tumor marker levels increased.We changed the endocrine therapy to fulvestrant(500mg/ month).For the next 2 years and 6 months, this therapy was effective.Her axillary lymph node metastases disappeared and tumor size decreased(60%).She underwent muscle-preserving mastectomy plus axillary lymph node dissection.The pathological diagnosis from the resected surgical specimen was confirmed as invasive ductal carcinoma, positive for ER and PgR, and negative for HER2/neu protein expression.The surgical margins were negative, and there was no metastasis in the lymph nodes.She was administered adjuvant endocrine therapy.Four years after surgery, she was well without metastasis.}, } @article {pmid29362312, year = {2018}, author = {Sakurai, K and Fujisaki, S and Kubota, H and Hara, Y and Suzuki, S and Adachi, K and Tomita, R and Enomoto, K and Hirano, T}, title = {[Synchronous and Unilateral Breast Cancers(Invasive Lobular Carcinoma and Non-Invasive Ductal Carcinoma) - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {45}, number = {1}, pages = {73-75}, pmid = {29362312}, issn = {0385-0684}, mesh = {Carcinoma, Ductal, Breast/*surgery ; Carcinoma, Lobular/*surgery ; Female ; Humans ; Mammography ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; Unilateral Breast Neoplasms/*pathology/*surgery ; }, abstract = {We report a case of synchronous and unilateral breast cancers in a 51-year-old female.A focal asymmetric right breast density was detected on breast cancer screening mammography.Ultrasonography showed a low echoic mass, 9mm in diameter, in the B area, and a second low echoic mass in the CD area of her right breast.A core needle biopsy of the B area mass led to a diagnosis of an invasive lobular carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), and negative for HER2/neu.One -percent of the tumor cells were Ki-67 positive.Her preoperative diagnosis was Stage I (T1N0M0).She underwent muscle-preserving mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the resected surgical specimen was invasive lobular carcinoma(B area), positive for ER, and negative for PgR and HER2/neu protein expression.From this, she was additionally diagnosed with non-invasive ductal carcinoma(CD area)that was posi- tive for ER, and negative for PgR and HER2/neu protein expression.The surgical margins were negative, and there were no sentinel lymph node metastases.These tumors were independent.She was given adjuvant endocrine therapy.Two years and 6 months after surgery, the patient was doing well and without metastases.}, } @article {pmid29362157, year = {2018}, author = {Uhlig, J and Fischer, U and Surov, A and Lotz, J and Wienbeck, S}, title = {Contrast-enhanced cone-beam breast-CT: Analysis of optimal acquisition time for discrimination of breast lesion malignancy.}, journal = {European journal of radiology}, volume = {99}, number = {}, pages = {9-16}, doi = {10.1016/j.ejrad.2017.12.003}, pmid = {29362157}, issn = {1872-7727}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Cone-Beam Computed Tomography/methods ; Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Mammography/methods ; Middle Aged ; Prospective Studies ; Ultrasonography, Mammary/methods ; }, abstract = {OBJECTIVE: To investigate the optimal acquisition time of contrast-enhanced cone-beam breast-CT (CBBCT) for best discrimination of breast lesion malignancy and whether contrast enhancement can aid in classification of tumor histology.

MATERIAL AND METHODS: The study included patients with BI-RADS 4 or 5 lesions identified on mammography and/or ultrasound. All patients were examined by non-contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) at 2 and 3min after contrast media (CM) injection. Lesion enhancement of suspicious breast lesions was evaluated in corresponding CBBCT slices.

RESULTS: A total of 31 patients with 57 breast lesions, 30 malignant and 27 benign, were included. Malignant breast lesions demonstrated higher contrast enhancement than benign breast lesions at both 2min and 3min CE-CBBCT (2min: 48.17 vs. 0.3 HU, p<0.001; 3min: 57.38 vs. 15.43 HU, p<0.001). Enhancement differences between malignant and benign breast lesions were largest at 2min CE-CBBCT. Ductal carcinoma in situ (DCIS) showed highest mean contrast enhancement among malignant breast lesions (100.93 HU at 3min CE-CBBCT, p=0.0314) compared to invasive carcinoma of no special type with DCIS component (55.82 HU at 3min CE-CBBCT) and invasive ductal carcinoma (52.31 HU at 3min CE-CBBCT).

CONCLUSIONS: The contrast enhancement on CE-CBBCT best discriminates between malignant and benign breast lesions at 2min after CM injection. The enhancement has the potential to differentiate histopathological subtypes, with highest enhancement among malignant lesions seen for DCIS.}, } @article {pmid29360854, year = {2018}, author = {Dolka, I and Czopowicz, M and Gruk-Jurka, A and Wojtkowska, A and Sapierzyński, R and Jurka, P}, title = {Diagnostic efficacy of smear cytology and Robinson's cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0191595}, pmid = {29360854}, issn = {1932-6203}, mesh = {Animals ; Biopsy ; Dog Diseases/*diagnosis/pathology ; Dogs ; Female ; Mammary Neoplasms, Animal/*diagnosis/pathology ; *Neoplasm Metastasis ; Sensitivity and Specificity ; Survival Analysis ; }, abstract = {Cytology is a simple, rapid, and inexpensive method used for pre-operative diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related to human breast cancer showed the Robinson's grading system-established for invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on cytological material-to not only closely correspond to the histopathological grading but also be helpful in assessing prognosis and selecting most suitable treatments before surgery. The objectives of this study were: to evaluate the accuracy of cytological diagnosis and cytological Robinson's grading system compared to the histopathological examination of CMTs; to compare of cytological features and cytomorphometric parameters with tumor behavior, as well as cytological and histological grading; and to determine an association of the Robinson's grading system and cytological background details with metastases, and patients' survival. We report substantial diagnostic accuracy in detecting simple types and high grade tumors. Cytological diagnosis of tumor behavior showed relatively low sensitivity and specificity compared to human studies, and this might be caused by the heterogeneous morphology of CMTs. The presence of mucosecretory material and extracellular matrix was not significantly associated with tumor behavior. We report a positive correlation between both grading systems and cytological features (included in Robinson's grading), the presence of necrotic debris, inflammation, and red blood cells. A negative correlation was determined only for the presence of extracellular matrix. The univariate and multivariate analyses confirmed a significantly higher risk of developing metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on cytology. In addition, these tumors were the most common cause of CMT-related deaths in dogs. Taken together, our findings suggest that the Robinson's method of cytological grading applied for malignant CMTs evaluated in cytological smears regardless of tumor type can be adapted to veterinary cytology. Additionally, some background features seem to aid malignancy assessment.}, } @article {pmid29358028, year = {2018}, author = {Santangelo, G and Garramone, F and Baiano, C and D'Iorio, A and Piscopo, F and Raimo, S and Vitale, C}, title = {Personality and Parkinson's disease: A meta-analysis.}, journal = {Parkinsonism & related disorders}, volume = {49}, number = {}, pages = {67-74}, doi = {10.1016/j.parkreldis.2018.01.013}, pmid = {29358028}, issn = {1873-5126}, mesh = {Adult ; Aged ; Aged, 80 and over ; Avoidance Learning/*physiology ; *Character ; Exploratory Behavior/*physiology ; *Extraversion, Psychological ; Female ; Humans ; Male ; Middle Aged ; Neuroticism/*physiology ; Parkinson Disease/complications/*physiopathology ; Personality Disorders/etiology/*physiopathology ; }, abstract = {INTRODUCTION: Personality changes are considered pre-motor features of Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were more introvert, apprehensive, and cautious than healthy subjects (HS), whereas other studies failed to disclose these behavioural traits. Some studies found mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in PD patients. To better clarify the personality profile in PD we performed a meta-analysis on studies exploring such topic according to both Cloninger's Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis included 17 studies evaluating the personality in PD patients compared with HS. The outcomes were the dimensions of the temperament and character of the PM and personality traits of BFM. Effect sizes from data reported in the primary studies were computed using Hedges'g unbiased approach. Heterogeneity among the studies and publication bias were assessed. Meta-regressions were conducted with age at evaluation, gender, schooling, and type of personality trait tools as moderators.

RESULTS: As for PM, PD patients scored higher on HA and lower on NS than HS. No difference was found on Reward Dependence, Perseverance/Persistence and on character level. As for BFM, higher levels of Neuroticism, but lower levels of Openness and Extraversion were associated with PD.

DISCUSSION: The personality profile in PD is characterized by high Neuroticism and HA, and by low Openness, Extraversion and NS. The personality profile delineated in the present study on PD patients seems to reflect the premorbid one and might contribute to development and persistence of affective disorders.}, } @article {pmid29356019, year = {2018}, author = {Shalaby, N and Al-Ebraheem, A and Le, D and Cornacchi, S and Fang, Q and Farrell, T and Lovrics, P and Gohla, G and Reid, S and Hodgson, N and Farquharson, M}, title = {Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.}, journal = {Lasers in surgery and medicine}, volume = {50}, number = {3}, pages = {236-245}, doi = {10.1002/lsm.22795}, pmid = {29356019}, issn = {1096-9101}, mesh = {Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Female ; Humans ; *Margins of Excision ; Mastectomy ; Reproducibility of Results ; *Spectrometry, Fluorescence ; }, abstract = {PURPOSE: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure.

METHODS: A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery.

RESULTS: Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue.

CONCLUSION: The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. © 2018 Wiley Periodicals, Inc.}, } @article {pmid29353241, year = {2018}, author = {Jabs, M and Rose, AJ and Lehmann, LH and Taylor, J and Moll, I and Sijmonsma, TP and Herberich, SE and Sauer, SW and Poschet, G and Federico, G and Mogler, C and Weis, EM and Augustin, HG and Yan, M and Gretz, N and Schmid, RM and Adams, RH and Gröne, HJ and Hell, R and Okun, JG and Backs, J and Nawroth, PP and Herzig, S and Fischer, A}, title = {Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart.}, journal = {Circulation}, volume = {137}, number = {24}, pages = {2592-2608}, doi = {10.1161/CIRCULATIONAHA.117.029733}, pmid = {29353241}, issn = {1524-4539}, mesh = {Adaptor Proteins, Signal Transducing ; Angiopoietins/genetics/metabolism ; Animals ; CD36 Antigens/genetics/metabolism ; Calcium-Binding Proteins ; Endothelium, Vascular/cytology/*metabolism ; Fatty Acid-Binding Proteins/genetics/metabolism ; Fatty Acids/genetics/*metabolism ; Glucose/genetics/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Myocardium/*metabolism ; Myocytes, Cardiac/metabolism ; Neovascularization, Physiologic ; Receptors, Notch/genetics/*metabolism ; Ribosomal Protein S6 Kinases/genetics/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/genetics/metabolism ; *Vascular Remodeling ; }, abstract = {BACKGROUND: Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function.

METHODS: Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-jκ in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Delta-like 4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice.

RESULTS: Treatment of wild-type mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-jκ caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-jκ-mutant mice, lipase activity and transendothelial transport of long-chain fatty acids to muscle cells were impaired. In turn, lipids accumulated in the plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged the survival of endothelial-specific Rbp-jκ-deficient mice.

CONCLUSIONS: This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.}, } @article {pmid29350928, year = {2018}, author = {Liu, R and Zhao, L and Dai, W and Yang, C and Liang, X and Li, G}, title = {A Comparative Investigation of Proton Conductivities for Two Metal-Organic Frameworks under Water and Aqua-Ammonia Vapors.}, journal = {Inorganic chemistry}, volume = {57}, number = {3}, pages = {1474-1482}, doi = {10.1021/acs.inorgchem.7b02851}, pmid = {29350928}, issn = {1520-510X}, abstract = {Our investigation on the proton conductivities of two water-stable isostructural 3D Co(II) MOFs, {[Co3(DMPhIDC)2(H2O)6]·2H2O} n (1) [DMPhH3IDC = 2-(3,4-dimethylphenyl)-imidazole-4,5-dicarboxylic acid] and {[Co3(m-BrPhIDC)2(H2O)6]·2H2O} (2) [m-BrPhH3IDC = 2-(m-bromophenyl)-imidazole-4,5-dicarboxylic acid], under water or aqua-ammonia vapor shows that the optimized proton conductivities of both 1 and 2 under aqua-ammonia vapor are 4.41 × 10[-3] S·cm[-1] and 5.07 × 10[-4] S·cm[-1] (at aqua-ammonia vapor from 1.5 M NH3·H2O solution and 100 °C), respectively, which are approximately 1 order of magnitude greater than those maximum values (8.91 × 10[-4] S·cm[-1] and 7.64 × 10[-5] S·cm[-1]) under water vapor (at 98% RH and 100 °C). The plausible proton pathways and mechanisms of the MOFs have been proposed in terms of the structural analyses, activation energy calculations, water and NH3 vapor absorptions, and PXRD determinations.}, } @article {pmid29350308, year = {2018}, author = {Ory, V and Kietzman, WB and Boeckelman, J and Kallakury, BV and Wellstein, A and Furth, PA and Riegel, AT}, title = {The PPARγ agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ.}, journal = {Breast cancer research and treatment}, volume = {169}, number = {1}, pages = {47-57}, pmid = {29350308}, issn = {1573-7217}, support = {P30CA051008//National Cancer Institute/ ; RO1CA205632//National Institutes of Health/ ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA205632/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; CA009686//T32 Training Grant in Tumor Biology/ ; R01 CA112176/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/genetics/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Neoplasm Invasiveness/genetics/pathology ; PPAR gamma/*genetics ; Thiazolidinediones/*administration & dosage ; Xenograft Model Antitumor Assays ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression.

METHODS: We utilized the high-affinity PPARγ agonist, efatutazone, to activate endogenous PPARγ in a well-defined model for the progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and 3D conditions. We studied the effects of activated PPARγ on DCIS progression in MCFDCIS xenograft and C3(1)/Tag transgenic mice treated with 30 mg/kg of efatutazone.

RESULTS: In vitro, efatutazone did not alter the MCFDCIS cell proliferation but induced phenotypic and gene expression changes, indicating that activated PPARγ is able to differentiate MCFDCIS cells into more luminal and lactational-like cells. In addition, MCFDCIS tumorsphere formation in 3D was reduced by PPARγ activation. In vivo, efatutazone-treated MCFDCIS tumors exhibited fat deposition along with upregulation of PPARγ responsive genes in both epithelial and stromal compartments, suggesting features of milk-producing mammary epithelial cell differentiation. The efatutazone-treated lesions were less invasive with fewer CD44+/p63+ basal progenitor cells. PPARγ activation downregulated Akt phosphorylation in these tumors, although the ERK pathway remained unchanged. Similar trends in gene expression changes consistent with lactational and luminal cell differentiation were observed in the C3(1)/Tag mouse model after efatutazone treatment.

CONCLUSIONS: Our data suggest that activation of the PPARγ pathway differentiates DCIS lesions and may be a useful approach to delay DCIS progression.}, } @article {pmid29349758, year = {2018}, author = {Feinberg, J and Wetstone, R and Greenstein, D and Borgen, P}, title = {Is DCIS Overrated?.}, journal = {Cancer treatment and research}, volume = {173}, number = {}, pages = {53-72}, doi = {10.1007/978-3-319-70197-4_5}, pmid = {29349758}, issn = {0927-3042}, mesh = {Breast Neoplasms/diagnosis/mortality/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/mortality/pathology/*therapy ; Female ; Gene Expression Profiling ; Humans ; Neoplasm Invasiveness ; }, abstract = {Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC), comprises just over 20% of breast cancer cases diagnosed each year in the USA. Most patients are treated with local excision of the disease followed by whole breast radiation therapy. Total mastectomy is not an uncommon approach, and total mastectomy with a contralateral risk-reducing mastectomy has been on the rise in the past decade. In estrogen receptor-positive disease, patients are often offered endocrine ablative therapy with a selective estrogen receptor modulator or an aromatase inhibitor as both treatment and prevention. Local regional treatment options have no impact upon ultimate overall survival. Long-term survival rates are higher in patients with DCIS than with any other form of the disease. Are these strikingly high success rates a testament to effective treatment strategies or is there a significant subset of DCIS that was unlikely to ever progress to invasive ductal carcinoma? DCIS was not seen in the US prior to the advent of screening mammography. When compared to other countries, the USA has the highest utilization of screening mammography and the incidence rate of DCIS. Other lines of evidence include autopsy series examining the breast tissue of women who died of other causes, missed-diagnosis series and current retrospective reviews of DCIS, all align in support of the concept of DCIS as indolent in the majority of cases [3-14]. The evidence suggests that both patient and physician misconceptions about DCIS have led to overdiagnosis and over-treatment of DCIS. Recently, a gene expression profiling tool (12 gene assay, Oncotype DCIS) has emerged that shows considerable promise in predicting class in DCIS patients.}, } @article {pmid29348822, year = {2017}, author = {Abdel-Fatah, TMA and Rees, RC and Pockley, AG and Moseley, P and Ball, GR and Chan, SYT and Ellis, IO and Miles, AK}, title = {The localization of pre mRNA splicing factor PRPF38B is a novel prognostic biomarker that may predict survival benefit of trastuzumab in patients with breast cancer overexpressing HER2.}, journal = {Oncotarget}, volume = {8}, number = {68}, pages = {112245-112257}, pmid = {29348822}, issn = {1949-2553}, abstract = {Cancer biomarkers that can define disease status and provide a prognostic insight are essential for the effective management of patients with breast cancer (BC). The prevalence, clinicopathological and prognostic significance of PRPF38B expression in a consecutive series of 1650 patients with primary invasive breast carcinoma were examined using immunohistochemistry. Furthermore, the relationship(s) between clinical outcome and PRPF38B expression was explored in 627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with HER2-overexpressing disease. Membranous expression of PRPF38B was observed in 148/1388 (10.7%) cases and was significantly associated with aggressive clinicopathological features, including high grade, high mitotic index, pleomorphism, invasive ductal carcinoma of no specific type (IDC-NST), ER-negative, HER2-overexpression and p53 mutational status (all p < 0.01). In patients with ER-negative disease receiving chemotherapy, nuclear expression of PRPF38B was significantly associated with a reduced risk of relapse (p = 0.0004), whereas membranous PRPF38B expression was significantly associated with increased risk of relapse (p = 0.004; respectively) at a 5 year follow-up. When patients were stratified according to ER-negative/HER2-positive status, membranous PRPF38B expression was associated with a higher risk of relapse in those patients that did not receive trastuzumab therapy (p = 0.02), whereas in those patients with ER-negative/HER2-positive disease that received trastuzumab adjuvant therapy, membranous PRPF38B expression associated with a lower risk of relapse (p = 0.00018). Nuclear expression of PRPF38B is a good prognostic indicator in both ER-negative patients and ER-negative/HER2-positive BC (breast cancer) patients, whereas membranous localisation of PRPF38B is a poor prognostic biomarker that predicts survival benefit from trastuzumab therapy in patients with ER-negative/HER2-overexpressing BC.}, } @article {pmid29347771, year = {2017}, author = {Rubinson, M and Levit-Binnun, N and Peled, A and Naim-Feil, J and Freche, D and Moses, E}, title = {Hierarchy measurement for modeling network dynamics under directed attacks.}, journal = {Physical review. E}, volume = {96}, number = {5-1}, pages = {052307}, doi = {10.1103/PhysRevE.96.052307}, pmid = {29347771}, issn = {2470-0053}, abstract = {A fundamental issue in the dynamics of complex systems is the resilience of the network in response to targeted attacks. This paper explores the local dynamics of the network attack process by investigating the order of removal of the nodes that have maximal degree, and shows that this dynamic network response can be predicted from the graph's initial connectivity. We demonstrate numerically that the maximal degree M(τ) of the network at time step τ decays exponentially with τ via a topology-dependent exponent. Moreover, the order in which sites are removed can be approximated by considering the network's "hierarchy" function h, which measures for each node V_{i} how many of its initial nearest neighbors have lower degree versus those that have a higher one. Finally, we show that the exponents we identified for the attack dynamics are related to the exponential behavior of spreading activation dynamics. The results suggest that the function h, which has both local and global properties, is a novel nodal measurement for network dynamics and structure.}, } @article {pmid29345622, year = {2018}, author = {Valero, A and Navarro, AM and Del Cuvillo, A and Alobid, I and Benito, JR and Colás, C and de Los Santos, G and Fernández Liesa, R and García-Lliberós, A and González-Pérez, R and Izquierdo-Domínguez, A and Jurado-Ramos, A and Lluch-Bernal, MM and Montserrat Gili, JR and Mullol, J and Puiggròs Casas, A and Sánchez-Hernández, MC and Vega, F and Villacampa, JM and Armengot-Carceller, M and Dordal, MT and , }, title = {Position paper on nasal obstruction: evaluation and treatment.}, journal = {Journal of investigational allergology & clinical immunology}, volume = {28}, number = {2}, pages = {67-90}, doi = {10.18176/jiaci.0232}, pmid = {29345622}, issn = {1018-9068}, mesh = {Animals ; Humans ; Nasal Cavity/drug effects ; Nasal Obstruction/*drug therapy ; Quality of Life ; Rhinomanometry/methods ; Rhinometry, Acoustic/methods ; }, abstract = {Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.}, } @article {pmid29345290, year = {2018}, author = {Nowak, A and Grzegrzółka, J and Kmiecik, A and Piotrowska, A and Matkowski, R and Dzięgiel, P}, title = {Role of nestin expression in angiogenesis and breast cancer progression.}, journal = {International journal of oncology}, volume = {52}, number = {2}, pages = {527-535}, doi = {10.3892/ijo.2017.4223}, pmid = {29345290}, issn = {1791-2423}, mesh = {Breast Neoplasms/*blood supply/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/metabolism/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic ; Nestin/genetics/*metabolism ; SOXF Transcription Factors/metabolism ; Triple Negative Breast Neoplasms/blood supply/metabolism/pathology ; }, abstract = {Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.}, } @article {pmid29344435, year = {2017}, author = {Akhtar, A and Ratra, A and Puckett, Y and Sheikh, AB and Ronaghan, CA}, title = {Synchronous Uterine Metastases from Breast Cancer: Case Study and Literature Review.}, journal = {Cureus}, volume = {9}, number = {11}, pages = {e1840}, pmid = {29344435}, issn = {2168-8184}, abstract = {Breast cancer rarely metastasizes to the uterus. Here, we report two breast cancer patients with synchronous metastases to the uterus. Case 1 highlights a 46-year-old female with invasive ductal carcinoma who presented with a breast mass and was found to have uterine enlargement on positron emission tomography (PET) scan. Biopsy revealed a metastatic 4 mm focus of breast cancer in the background of endometrial hyperplasia. Case 2 reports a 62-year-old postmenopausal female diagnosed with lobular carcinoma of the breast following an abnormal screening mammogram. A routine pap smear necessitated further workup, revealing simultaneous endometrial and cervical metastasis. Both patients did not have any gynecologic symptoms and presented a diagnostic challenge.}, } @article {pmid29344186, year = {2017}, author = {Li, P and Zhao, M and Qi, X and Zhu, X and Dai, J}, title = {Downregulation of klotho β is associated with invasive ductal carcinoma progression.}, journal = {Oncology letters}, volume = {14}, number = {6}, pages = {7443-7448}, pmid = {29344186}, issn = {1792-1074}, abstract = {Klotho β (KLB) is a single-pass transmembrane protein measuring 1,043 amino acids in length that shares 41.2% homology with klotho α (KLA). KLB is a co-receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4) pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor suppressor in human breast cancer; however, little is known regarding the role of KLB in breast cancer. In the present study, through an immunohistochemical analysis of invasive ductal carcinoma tissue arrays, low KLB expression was identified in invasive ductal carcinoma samples compared with paired adjacent non-tumorous breast tissues (82 cases). In invasive ductal carcinoma tissues, KLB expression was negatively associated with pathological grade and lymph node metastasis. In 42 cases of paired microdissected breast specimens, the condition of the KLB gene allele was examined to determine the loss of heterozygosity (LOH), and selective LOH was identified at the KLB locus in 57.1% of primary tumors. These data suggest that KLB may be associated with the progression and metastasis of invasive ductal carcinoma, and therefore have clinical and therapeutic importance.}, } @article {pmid29343538, year = {2018}, author = {Ghandour, RA and Colson, C and Giroud, M and Maurer, S and Rekima, S and Ailhaud, G and Klingenspor, M and Amri, EZ and Pisani, DF}, title = {Impact of dietary ω3 polyunsaturated fatty acid supplementation on brown and brite adipocyte function.}, journal = {Journal of lipid research}, volume = {59}, number = {3}, pages = {452-461}, pmid = {29343538}, issn = {1539-7262}, mesh = {Adipose Tissue, Brown/*drug effects/metabolism ; Adipose Tissue, White/*drug effects/metabolism ; Cells, Cultured ; *Dietary Supplements ; Fatty Acids, Omega-3/*administration & dosage/*pharmacology ; Humans ; Oxylipins/metabolism ; Receptors, Prostaglandin/agonists/metabolism ; }, abstract = {The recent characterization of functional brown adipose tissue in adult humans has opened new perspectives for regulation of energy expenditure with respect to obesity and diabetes. Furthermore, dietary recommendations have taken into account the insufficient dietary intake of ω3 PUFAs and the concomitant excessive intake of ω6 PUFA associated with the occurrence of overweight/obesity. We aimed to study whether ω3 PUFAs could play a role in the recruitment and function of energy-dissipating brown/brite adipocytes. We show that ω3 PUFA supplementation has a beneficial effect on the thermogenic function of adipocytes. In vivo, a low dietary ω6:ω3 ratio improved the thermogenic response of brown and white adipose tissues to β3-adrenergic stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS adipocytes. We pinpointed the ω6-derived eicosanoid prostaglandin (PG)F2α as the molecular origin because the effects were mimicked with a specific PGF2α receptor agonist. PGF2α level in hMADS adipocytes was reduced in response to ω3 PUFA supplementation. The recruitment of thermogenic adipocytes is influenced by the local quantity of individual oxylipins, which is controlled by the ω6:ω3 ratio of available lipids. In human nutrition, energy homeostasis may thus benefit from the implementation of a more balanced dietary ω6:ω3 ratio.}, } @article {pmid29339079, year = {2018}, author = {Kim, KW and Kuzmiak, CM and Kim, YJ and Seo, JY and Jung, HK and Lee, MS}, title = {Diagnostic Usefulness of Combination of Diffusion-weighted Imaging and T2WI, Including Apparent Diffusion Coefficient in Breast Lesions: Assessment of Histologic Grade.}, journal = {Academic radiology}, volume = {25}, number = {5}, pages = {643-652}, doi = {10.1016/j.acra.2017.11.011}, pmid = {29339079}, issn = {1878-4046}, mesh = {Adenocarcinoma, Mucinous/*diagnostic imaging/pathology ; Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Contrast Media ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; }, abstract = {PURPOSE: This study aimed to compare the diagnostic values of a combination of diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to evaluate the correlation of DWI with the histologic grade in breast cancer.

MATERIALS AND METHODS: This study evaluated a total of 169 breast lesions from 136 patients who underwent both DCE-MRI and DWI (b value, 1000s/mm[2]). Morphologic and kinetic analyses for DCE-MRI were classified according to the Breast Imaging-Reporting and Data System. For the DWI-T2WI set, a DWI-T2WI score for lesion characterization that compared signal intensity of DWI and T2WI (benign: DWI-T2WI score of 1, 2; malignant: DWI-T2WI score of 3, 4, 5) was used. The diagnostic values of DCE-MRI, DWI-T2WI set, and combined assessment of DCE and DWI-T2WI were calculated.

RESULTS: Of 169 breast lesions, 48 were benign and 121 were malignant (89 invasive ductal carcinoma, 24 ductal carcinoma in situ, 4 invasive lobular carcinoma, 4 mucinous carcinoma). The mean apparent diffusion coefficient (ADC) of invasive ductal carcinoma (0.92 ± 0.19 × 10[-3] mm[2]/s) and ductal carcinoma in situ (1.11 ± 0.13 × 10[-3] mm[2]/s) was significantly lower than the value seen in benign lesions (1.36 ± 0.22 × 10[-3] mm[2]/s). The specificity, positive predictive value (PPV), and accuracy of DWI-T2WI set and combined assessment of DCE and DWI-T2WI (specificity, 87.5% and 91.7%; PPV, 94.3% and 96.2%; accuracy, Az = 0.876 and 0.922) were significantly higher than those of the DCE-MRI (specificity, 45.8%; PPV, 81.7%; accuracy, Az = 0.854; P < .05). A low ADC value and the presence of rim enhancement were associated with a higher histologic grade cancer (P < .05).

CONCLUSION: Combining DWI, T2WI, and ADC values provides increased accuracy for differentiation between benign and malignant lesions, compared with DCE-MRI. A lower ADC value was associated with a higher histologic grade cancer.}, } @article {pmid29336321, year = {2018}, author = {Yahia, R and Zaoui, C and Derbale, W and Boudi, H and Chebloune, Y and Sahraoui, T and Elkebir, FZ}, title = {[Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria].}, journal = {Annales de biologie clinique}, volume = {76}, number = {1}, pages = {75-80}, doi = {10.1684/abc.2017.1312}, pmid = {29336321}, issn = {1950-6112}, mesh = {Adult ; Algeria/epidemiology ; Breast Neoplasms/complications/epidemiology/genetics/*virology ; Carcinoma, Ductal, Breast/complications/epidemiology/genetics/*virology ; Enzyme-Linked Immunosorbent Assay ; Epstein-Barr Virus Infections/*diagnosis/epidemiology ; Epstein-Barr Virus Nuclear Antigens/analysis/*isolation & purification/metabolism ; Female ; Herpesvirus 4, Human/genetics/*isolation & purification/metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Molecular Typing/methods ; RNA, Viral/genetics/*isolation & purification/metabolism ; }, abstract = {Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.}, } @article {pmid29330212, year = {2018}, author = {Schroeder, MC and Rastogi, P and Geyer, CE and Miller, LD and Thomas, A}, title = {Early and Locally Advanced Metaplastic Breast Cancer: Presentation and Survival by Receptor Status in Surveillance, Epidemiology, and End Results (SEER) 2010-2014.}, journal = {The oncologist}, volume = {23}, number = {4}, pages = {481-488}, pmid = {29330212}, issn = {1549-490X}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/epidemiology/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/epidemiology/metabolism/mortality/pathology ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; SEER Program/*statistics & numerical data ; Survival Analysis ; }, abstract = {BACKGROUND: Metaplastic breast cancer (MBC) is a rare disease subtype characterized by an aggressive clinical course. MBC is commonly triple negative (TN), although hormone receptor (HR) positive and human epidermal growth receptor 2 (HER2) positive cases do occur. Previous studies have reported similar outcomes for MBC with regard to HR status. Less is known about outcomes for HER2 positive MBC.

MATERIALS AND METHODS: Surveillance, Epidemiology, and End Results Program data were used to identify women diagnosed 2010-2014 with MBC or invasive ductal carcinoma (IDC). Kaplan-Meier curves estimated overall survival (OS) and multivariate Cox models were fitted. For survival analyses, only first cancers were included, and 2014 diagnoses were excluded to allow for sufficient follow-up.

RESULTS: Our MBC sample included 1,516 women. Relative to women with IDC, women with MBC were more likely to be older (63 vs. 61 years), black (16.0% vs. 11.1%), and present with stage III disease (15.6% vs. 10.8%). HER2 positive and HER2 negative/HR positive MBC tumors represented 5.2% and 23.0% of cases. For MBC overall, 3-year OS was greatest for women with HER2 positive MBC (91.8%), relative to women with TN (75.4%) and HER2 negative/HR positive MBC (77.1%). This difference was more pronounced for stage III MBC, for which 3-year OS was 92.9%, 47.1%, and 42.2% for women with HER2 positive, TN, and HER2 negative/HR positive MBC, respectively. A multivariate Cox model of MBC demonstrated that HER2 positive tumors (relative to TN) were associated with improved survival (hazard ratio = 0.32, 95% confidence interval [CI] 0.13-0.79). In a second Cox model of exclusively HER2 positive tumors, OS did not differ between MBC and IDC disease subtypes (hazard ratio = 1.16, 95% CI 0.48-2.81).

CONCLUSION: In this contemporary, population-based study of women with MBC, HER2 but not HR status was associated with improved survival. Survival was similar between HER2 positive MBC and HER2 positive IDC. This suggests HER2 positive MBC is responsive to HER2-directed therapy, a finding that may offer insights for additional therapeutic approaches to MBC.

IMPLICATIONS FOR PRACTICE: This population-based study reports recent outcomes, by receptor status, for women with metaplastic breast cancer. Survival in metaplastic breast cancer is not impacted by hormone receptor status. To the authors' knowledge, this is the first report indicating that women with human epidermal growth receptor 2 (HER2) positive metaplastic breast cancer have survival superior to women with HER2 negative metaplastic breast cancer and survival similar to women with HER2 positive invasive ductal carcinoma. This information can be used for counseling patients diagnosed with metaplastic breast cancer. Further understanding of HER2 positive metaplastic breast cancer could offer insights for the development of therapeutic approaches to metaplastic breast cancer more broadly.}, } @article {pmid29327767, year = {2017}, author = {Darouich, S and El Amine El Hadj, O and Betaieb, I and Goucha, A and Dhiab, T and Rahal, K and Gamoudi, A and El May, A}, title = {Triple negative breast cancer: A clinico-epidemiological and histopronostic study of 90 cases.}, journal = {La Tunisie medicale}, volume = {95}, number = {1}, pages = {37-44}, pmid = {29327767}, issn = {0041-4131}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology/*pathology/therapy ; Female ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/pathology/therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/diagnosis/*epidemiology/*pathology/therapy ; Tunisia/epidemiology ; }, abstract = {PURPOSE: The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women.

METHODS: We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis.

RESULTS: TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease.

CONCLUSION: TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.}, } @article {pmid29325355, year = {2018}, author = {Hua, B and Lu, X and Xiao, WZ and Yang, X and He, SR and Wang, Z}, title = {[Comparison of prognosis between invasive micropapillary carcinoma and invasive ductal carcinoma of breast: a single center, retrospective case-control study].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {56}, number = {1}, pages = {56-60}, doi = {10.3760/cma.j.issn.0529-5815.2018.01.013}, pmid = {29325355}, issn = {0529-5815}, mesh = {*Breast Neoplasms/diagnosis/surgery ; *Carcinoma, Ductal, Breast/diagnosis/surgery ; *Carcinoma, Papillary/diagnosis/surgery ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Prognosis ; Retrospective Studies ; }, abstract = {Objective: To elucidate the clinicopathological characters and prognostic factors of invasive micropapillary carcinoma of the breast (IMPC) by compared with invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods: The retrospective study was performed with female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy from June 2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or pure IMPC patients and 93 pure IDC patients(admitted in the same center from October 2008 to January 2016) were matched for tumor stage, nodal status and age. Follow-up was done every 3 to 6 months postoperatively. The deadline was July 31, 2016. The curves of disease free survival and overall survival were drawn by the Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables that were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. The χ(2) test or Fisher's exact test was used to compare distributions across 2 groups and the Mann-Whitney U test or t test was used to analyze the medians or means of 2 groups. Results: With exact matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%, χ(2)=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, χ(2)=-2.690, P=0.007) were both significantly higher in patients with IMPC than that in IDC group, but the survival between the two pathological types were not significantly different (all P>0.05). The percent of IMPC component didn't influence the clinicopathologic characters (all P >0.05), but a significantly longer median disease free survival (χ(2)=11.731, P=0.001) when the patients had more than 50% of IMPC component was found. Conclusions: Higher rates of LVI and histological grade 3 were found in IMPC than that in IDC, but the survival was comparable between the two groups. A longer DFS occurred in patients with IMPC component more than 50%.}, } @article {pmid29325253, year = {2018}, author = {Xu, C and Pan, BJ and Ping, GQ and Hua, HJ and Song, GX and Zhang, ZH}, title = {[Expression of PD-L1 and clinicopathologic correlation in invasive ductal carcinoma of breast with nodal metastasis].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {47}, number = {1}, pages = {59-60}, doi = {10.3760/cma.j.issn.0529-5807.2018.01.012}, pmid = {29325253}, issn = {0529-5807}, } @article {pmid29324959, year = {2018}, author = {Romanholo, HSB and Souza, EA and Ramos Júnior, AN and Kaiser, ACGCB and Silva, IOD and Brito, AL and Vasconcellos, C}, title = {Surveillance of intradomiciliary contacts of leprosy cases: perspective of the client in a hyperendemic municipality.}, journal = {Revista brasileira de enfermagem}, volume = {71}, number = {1}, pages = {163-169}, doi = {10.1590/0034-7167-2016-0607}, pmid = {29324959}, issn = {1984-0446}, mesh = {Adolescent ; Adult ; Brazil/epidemiology ; Child ; Contact Tracing/methods ; Cross-Sectional Studies ; Female ; Humans ; Leprosy/*epidemiology/psychology ; Male ; Middle Aged ; Patients/*psychology ; *Perception ; Population Surveillance/*methods ; }, abstract = {OBJECTIVE: To characterize approach methods for intradomiciliary contacts (IdC) of leprosy cases resident in Northern Brazil, during 2001-2012.

METHOD: A cross-sectional and descriptive study in the state of Rondônia. Included IdC of leprosy cases diagnosed/reported in SINAN-Ministry of Health (MS), 2001-2012. A semi-structured instrument was applied to the IdCs, with six interventions: complete dermatological examination; complete neurological examination; BCG vaccination; instructions for return to the health unit; BCG guidance; and guidance to mobilize other contacts.Results: From a total of 459 IdCs included, failure to perform the dermatological examination was reported by 191 people (41.6%) and the neurological examination, by 252 (54.9%); 138 (30.1%) did not have BCG indicated and 122 (26.6%) did not receive guidelines; 257 (56.0%) were not advised to return for a new evaluation/follow-up and 186 (40.5%) were not asked to mobilize other contacts.

CONCLUSION: Despite the favorable indicators of IdC examination coverage in the state, the evaluation process presents patterns that indicate operational quality failures.}, } @article {pmid29322559, year = {2018}, author = {Zhang, S and Seiler, S and Wang, X and Madhuranthakam, AJ and Keupp, J and Knippa, EE and Lenkinski, RE and Vinogradov, E}, title = {CEST-Dixon for human breast lesion characterization at 3 T: A preliminary study.}, journal = {Magnetic resonance in medicine}, volume = {80}, number = {3}, pages = {895-903}, pmid = {29322559}, issn = {1522-2594}, support = {R21 EB020245/EB/NIBIB NIH HHS/United States ; }, mesh = {Adipose Tissue/*diagnostic imaging/pathology ; Algorithms ; Biopsy ; Breast/*diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Diagnosis, Computer-Assisted ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Ki-67 Antigen/metabolism ; Least-Squares Analysis ; Lipids/chemistry ; *Magnetic Resonance Imaging ; Neoplasms/diagnostic imaging/metabolism ; Phantoms, Imaging ; Radiology ; Water ; }, abstract = {PURPOSE: CEST MRI for breast lesion characterization is promising. However, artifacts are prone to develop in breast CEST imaging due to strong lipid signals. The aims of the study are: 1) to develop and validate the CEST-Dixon imaging sequence for simultaneous water-fat separation and B0 mapping; 2) use the CEST-Dixon method to characterize suspicious lesions in patients undergoing percutaneous biopsy.

METHODS: The gradient-echo multi-echo Dixon acquisition is used to create fat-free CEST and B0 maps. The sequence has been validated in phantoms and in vivo. Five healthy volunteers and ten patients were scanned to compare the CEST contrast in three frequency ranges centered at 1, 2 and 3.5 ppm. The correlation between the CEST contrast and pathology markers (tumor type, ER status, Ki-67) was also investigated by stratifying the patients into ER-negative invasive ductal carcinoma (IDC) (more aggressive), ER-positive IDC (less aggressive) and benign groups.

RESULTS: The CEST-Dixon sequence shows homogenous fat removal in the water-only images. The ER-negative IDC tissues display a trend to higher CEST contrast in all three frequencies ranges, while the ER-positive IDC, benign and normal tissues have lower CEST contrast. No significant differences were observed between the ER-positive IDC, benign and normal tissues. Of the three frequencies ranges, the CEST contrasts at 1 ppm are high in the ER-negative IDC group, have the largest difference between the ER-negative IDC and the other groups and have the highest correlation with Ki-67.

CONCLUSIONS: Breast CEST-Dixon imaging shows potential to differentiate more aggressive from less aggressive cancers.}, } @article {pmid29320752, year = {2018}, author = {Li, YH and Liu, HT and Xu, J and Xing, AY and Zhang, J and Wang, YW and Yin, G and Gao, P}, title = {The value of detection of S100A8 and ASAH1 in predicting the chemotherapy response for breast cancer patients.}, journal = {Human pathology}, volume = {74}, number = {}, pages = {156-163}, doi = {10.1016/j.humpath.2018.01.004}, pmid = {29320752}, issn = {1532-8392}, mesh = {Acid Ceramidase/*metabolism ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Calgranulin A/*metabolism ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Female ; Humans ; Lymphatic Metastasis/*pathology ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; Triple Negative Breast Neoplasms/*drug therapy/metabolism/pathology ; }, abstract = {Chemotherapy plays an important role in the treatment of breast cancer. However, chemoresistance remains the main obstacle for effective treatment, leading to poor prognosis. This study aims to investigate the value of detection of S100A8 and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were used to assess the chemotherapy response in breast cancers. The expression of S100A8 and ASAH1, as well as ER, PR, HER2 and Ki-67 were assessed by immunohistochemical staining in 120 cases of non-special type invasive ductal carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast cancers than chemoresistant ones. Moreover, S100A8 expression was significantly correlated with the molecular subtypes and histological grade, but not with patients' age, tumor size and lymph nodes status. However, there was no significant difference in ASAH1 expression between chemoresistant and chemosensitive group. We also found that higher ASAH1 expression was correlated with positive lymph nodes status, but not with age, tumor size, molecular subtypes and histological grade. S100A8 was valuable in predicting chemotherapy response in breast cancers. The expression of ASAH1 was associated significantly with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to predict patients' lymph nodes status in breast cancers.}, } @article {pmid29312836, year = {2017}, author = {Widya, RL and Rodrigues, MF and Truong, PT and Watson, PH and Weir, LM and Knowling, MA and Wai, ES}, title = {Malignant Epithelial Transformation in Phyllodes Tumor: A Population-Based Case Series.}, journal = {Cureus}, volume = {9}, number = {11}, pages = {e1815}, pmid = {29312836}, issn = {2168-8184}, abstract = {Background Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial neoplasm. Malignant epithelial transformation in PT is rare. This study reports clinicopathologic characteristics and outcomes of patients with malignant epithelial transformation in PT. Methods From an institutional database of 183 patients with newly diagnosed PT referred to a Canadian provincial cancer institution between 1999 and 2014, 11 cases of PT with concomitant in situ or invasive carcinoma were identified. Descriptive analysis was performed to document the characteristics, treatment and outcomes of this cohort. Results Prevalence of malignant epithelial transformation in PT was 6.0%. Median (range) age was 54 (35-75) years. Types of carcinoma were ductal carcinoma in situ (DCIS) (n = 6), lobular carcinoma in situ (n = 4), and invasive ductal carcinoma (IDC) (n = 1). Median PT size was 5 (1-15) cm. Three PTs were classified as benign (27%), five as borderline (45%), and three as malignant (27%). Mastectomy was performed in six (55%) and breast conserving surgery in five (45%) patients. Hormonal therapy was used in two cases: one with a 1 cm, grade 2 DCIS, and one with an 11 cm, grade 1 IDC, the latter also receiving radiotherapy. Mean follow-up duration was 54 (6-175) months. None of the cases showed any evidence of disease after treatment at the time of their last follow-up. Conclusion This case series showed a higher prevalence of malignant epithelial transformation in PT than reported in previous literature. Outcomes were favourable despite the presence of either in situ or invasive carcinoma within PT.}, } @article {pmid29312521, year = {2017}, author = {Do, SI and Kim, HS and Kim, K and Lee, H and Do, IG and Kim, DH and Chae, SW and Sohn, JH}, title = {Predictive and prognostic value of sphingosine kinase 1 expression in patients with invasive ductal carcinoma of the breast.}, journal = {American journal of translational research}, volume = {9}, number = {12}, pages = {5684-5695}, pmid = {29312521}, issn = {1943-8141}, abstract = {Sphingosine kinase 1 (SPHK1) has been found to be upregulated in many different types of human malignancy and plays a crucial role in cancer development and progression. However, the potential of SPHK1 to act as a predictive and prognostic biomarker in breast cancer remains to be clarified. In the present study, SPHK1 expression was evaluated in breast cancer cell lines and 224 breast cancer tissue samples using immunohistochemical staining. Compared to the normal mammary epithelial cell line MCF-10A, SPHK1 mRNA and protein expression levels increased in the breast cancer cell lines SK-BR-3, MDA-MB-231, MDA-MB-436, and MCF-7. Immunohistochemical staining revealed SPHK1 expression to be significantly increased in breast cancer tissue compared to normal breast tissue, with 85 (37.9%) of the 224 invasive ductal carcinomas (IDC) exhibiting high SPHK1 expression. High SPHK1 expression in IDC showed a significant association with higher histological grade, distant metastasis, and triple negativity, and was shown to be an independent predictor for distant metastasis development. In addition, patients with high SPHK1 expression had significantly lower progression-free survival and overall survival rates compared to those with low SPHK1 expression. Our data suggest that SPHK1 is involved in the development and progression of breast cancer and can serve as a potential predictive biomarker of distant metastasis and patient outcome.}, } @article {pmid29310379, year = {2017}, author = {Liu, J and Wei, H and Zhu, K and Lai, L and Han, X and Yang, Y}, title = {Male breast cancer and mantle cell lymphoma in a single patient: A case report and literature review.}, journal = {Medicine}, volume = {96}, number = {48}, pages = {e8911}, pmid = {29310379}, issn = {1536-5964}, mesh = {Adenocarcinoma/drug therapy/*pathology/surgery ; Aged ; Biopsy ; Breast Neoplasms, Male/drug therapy/*pathology/surgery ; Combined Modality Therapy ; Humans ; Lymphoma, Mantle-Cell/drug therapy/*pathology/surgery ; Male ; Mastectomy ; Neoplasm Grading ; Neoplasms, Multiple Primary/drug therapy/*pathology/surgery ; }, abstract = {RATIONALE: Although still relatively rare, multiple primary malignant neoplasms (MPMNs) have been increasingly reported in recent years.

A 65-year-old man was referred to our hospital for a painless, incidental left axillary lump. Ultrasound showed enlarged left axillary lymph nodes. An excisional biopsy was conducted on 3 lymph nodes. The pathological diagnosis was determined to be metastatic adenocarcinoma and mantle cell lymphoma (MCL) in the lymph nodes. Further physical examination of the patient yielded a 1.5-cm hard, left subareolar mass.

INTERVENTIONS AND OUTCOMES: The patient underwent modified radical mastectomy. The diagnosis was grade II invasive ductal carcinoma (stage IIA). The axillary lymph node showed MCL (stage I, group A), but not metastatic ductal carcinoma. The patient received chemotherapy, including 6 courses of CHOP (A chemotherapy protocol consists of cyclophosphamide 1.2 g day 1, doxorubicin 80 mg day 1, vindesine 4 mg day1, and prednisone 90 mg from day 1 to 5) for lymphoma and breast cancer. The patient was also administered endocrine therapy. After a 54-month follow-up, the patient was well with no evidence of disease.

LESSONS: MPMNs are easily misdiagnosed as a primary and metastatic tumor, leading to delayed or erroneous treatment. Male breast cancer in a patient with MCL is rare. Early diagnosis and proper therapy are necessary for an optimal prognosis. Further studies are required to define the mechanisms and risk factors of MPMNs.}, } @article {pmid29308284, year = {2017}, author = {Reynolds, TD and Mohan, V and Roy, M and Manghat, N and Adamali, H and Gunawardena, H}, title = {An unusual flare of anti-synthetase syndrome during concurrent trastuzumab therapy given for recurrent breast cancer.}, journal = {European journal of rheumatology}, volume = {4}, number = {4}, pages = {278-280}, pmid = {29308284}, issn = {2147-9720}, abstract = {We present the case of a patient with relapsing anti-synthetase syndrome (ASS) that may have been triggered by monoclonal antibody trastuzumab therapy given for breast cancer. A 52-year-old female with a history of anti-Jo1-associated ASS went into remission with glucocorticoids and mycophenolate mofetil. Her past history included invasive ductal carcinoma of the right breast that was fully treated six years prior to the onset of ASS. She subsequently developed recurrent right-sided breast cancer that was treated with right mastectomy and six cycles of cyclophosphamide-docetaxel chemotherapy. She commenced adjuvant trastuzumab and letrozole therapy, and following the sixth injection of trastuzumab, she was admitted with clinical features consistent with a flare of ASS, which included swinging fever, interstitial lung disease, myositis, and possible subclinical myocarditis, despite recent treatment with cyclophosphamide. She responded to intravenous IV methylprednisolone followed by increased doses of oral glucocorticoids, and she remains stable on immunomodulatory treatment and letrozole monotherapy given for breast cancer. This report provides a concise overview of ASS along with other cases of cardiac and pulmonary diseases attributed to trastuzumab therapy reported in the medical literature.}, } @article {pmid29308181, year = {2017}, author = {Alharbi, A and Aboasamh, G and Shafik, Y}, title = {Appendicular and breast cancers in an old lady: a case report.}, journal = {Journal of surgical case reports}, volume = {2017}, number = {12}, pages = {rjx251}, pmid = {29308181}, issn = {2042-8812}, abstract = {The presence of two or more malignant tumors of different histological entities in an individual is referred to as multiple primary malignant neoplasms (MPMN). These are becoming more frequently encountered and reported in clinical practice nowadays. Majority of MPMN are diagnosed in elderly, where senility might alter the management plan. Despite the increased reporting of MPMN in the literature, only a few elaborated on the management of such cases. Also, the combination of synchronous primary appendicular and breast cancers-to our knowledge-has never been reported. Here we present the first report of an appendicular adenocarcinoma synchronously presenting along with invasive ductal carcinoma of the breast. We highlight the diagnostic essentials and the multidisciplinary management approach including surgical excision and adjuvant therapy.}, } @article {pmid29307488, year = {2018}, author = {Casasent, AK and Schalck, A and Gao, R and Sei, E and Long, A and Pangburn, W and Casasent, T and Meric-Bernstam, F and Edgerton, ME and Navin, NE}, title = {Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.}, journal = {Cell}, volume = {172}, number = {1-2}, pages = {205-217.e12}, pmid = {29307488}, issn = {1097-4172}, support = {R01 CA169244/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Movement ; *Clonal Evolution ; Exome ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Sequence Analysis, DNA ; Single-Cell Analysis ; }, abstract = {Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.}, } @article {pmid29304834, year = {2018}, author = {Nzeangung, BA and Biwole, ME and Kadia, BM and Bechem, NN and Dimala, CA and Sone, AM}, title = {Evolutionary aspects of non-metastatic breast cancer after primary treatment in a sub-Saharan African setting: a 16-year retrospective review at the Douala general hospital, Cameroon.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {32}, pmid = {29304834}, issn = {1471-2407}, mesh = {Adult ; Africa South of the Sahara/epidemiology ; Aged ; Breast Neoplasms/*drug therapy/epidemiology/pathology/surgery ; Breast Neoplasms, Male/*drug therapy/epidemiology/pathology/surgery ; Cameroon/epidemiology ; Combined Modality Therapy ; Female ; Hospitals, General ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/epidemiology/pathology/surgery ; Survival Rate ; }, abstract = {BACKGROUND: Breast cancer has a high case fatality rate in sub-Saharan Africa, and this is chiefly because of late detection and inadequate treatment resources. Progressive renovations in diagnostic and management modalities of non-metastatic breast cancer (NMBC) have been noted in the region but there is paucity of data describing the clinical progress of patients with NMBC. This study sought to determine the rates of local relapse, distant metastasis and sequelae and the time span from initial treatment to the occurrence of these adverse events among patients with NMBC.

METHODS: This was a retrospective review of medical records of patients with histologically confirmed NMBC at the department of radiation therapy and oncology of the Douala General Hospital in Cameroon from the January 1997 to December 2012 period. Clinicopathological and treatment characteristics as well as occurrences of adverse events were studied.

RESULTS: A total of 260 cases were reviewed of which 224/260 (86.2%) had invasive ductal carcinoma. Surgery was performed on 258/260 cases (99.2%) with 187/258 (72.5%) being modified radical mastectomies. Various treatment combinations were used in up to 228/260 patients (87.5%) while surgery alone was the treatment in the remaining 32 cases (12.5%). Metastasis occurred in 142/260 cases (54.6%) of which 68/142 (26.2%) were local relapses and 74/142 (28.5%) were distant metastases. Among the cases of distant metastasis, 9.2% were bone, 8.5% lungs, 6.9% nodal, and 5.4% brain. Metastasis to multiple organs was noted in 4.7% of these cases. The median periods of occurrence of local relapse and distant metastases were 13 and 12 months respectively. Sequelae occurred in 26/260 cases (10%) and were noted after an average of 30 months. The main sequelae were lymphoedema (6.5%) and lung fibrosis (1.5%). At the end of the period under review, 118/260 patients (45.4%) were alive and disease-free with a median follow up time of 24 months.

CONCLUSIONS: Adverse events were frequent among patients who received primary treatment for NMBC. Available cancer therapeutic modalities ought to be supplemented with efficient strategies of follow-up and monitoring so as to optimize the care provided to these patients and improve on their survival.}, } @article {pmid29302899, year = {2018}, author = {Jalaly, JB and Sanati, S and Chernock, RD and Dibe, DG and El-Mofty, SK}, title = {Salivary Duct Carcinoma and Invasive Ductal Carcinoma of the Breast: A Comparative Immunohistochemical Study.}, journal = {Head and neck pathology}, volume = {12}, number = {4}, pages = {488-492}, pmid = {29302899}, issn = {1936-0568}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Salivary Gland Neoplasms/*diagnosis ; }, abstract = {Salivary duct carcinoma (SDC) is a high-grade salivary gland malignancy with great morphological resemblance to invasive ductal carcinoma (IDC) of the breast. Rarely, female patients may have a past history of both SDC and IDC. When these patients present with distant metastasis, accurate identification of the primary tumor is particularly difficult. Additionally, rare metastasis of SDC to the breast and IDC to the salivary (parotid) gland can also present a diagnostic challenge. Our aim was to develop an immunohistochemical panel that reliably distinguishes SDC from IDC. We included all SDCs diagnosed from 1989 to 2016 (23 cases) and 29 treatment naïve and histologically similar IDCs. All cases were stained with androgen receptor (AR), estrogen receptor-alpha (ER-α), progesterone receptor (PR), HER-2, CK5/6, p63, and beta-catenin. The great majority (> 90%) of both SDCs and IDCs reacted positively to AR. The main discrepancy in the immunohistochemical profiles was a distinctly different reactivity to ER-α, PR and HER-2. While 28 IDCs (96.6%) reacted positively to ER-α and/or PR, the majority expressing both (82.8%) with a moderate to strong staining intensity, only 2 SDCs expressed ER-α (8.7%) and 5 others expressed PR (21.7%) with only one case expressing both (P value < 0.05). On the other hand, 8 SDC (34.8%) were positive for HER-2 while none of the IDCs were positive (P value < 0.05). ER-α, PR, and HER-2 may be helpful to distinguish SDC from IDC. Positive reactivity to ER-α, PR or both and negative HER-2 favors a diagnosis of IDC while ER-α, PR negative, HER-2 positive tumors are more likely SDC.}, } @article {pmid29302820, year = {2018}, author = {Yamada, M and Sugiura, T and Okamura, Y and Ito, T and Yamamoto, Y and Ashida, R and Sasaki, K and Nagino, M and Uesaka, K}, title = {Microscopic Venous Invasion in Pancreatic Cancer.}, journal = {Annals of surgical oncology}, volume = {25}, number = {4}, pages = {1043-1051}, doi = {10.1245/s10434-017-6324-2}, pmid = {29302820}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*pathology/surgery ; Pancreatectomy/*mortality ; Pancreatic Neoplasms/*pathology/surgery ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Microscopic venous invasion (MVI) and the subsequent peripheral blood circulation of cancer cells are considered to be the primary route for systemic dissemination of pancreatic cancer.

METHODS: Patients who underwent pancreatectomy for invasive ductal carcinoma of the pancreas between January 2007 and December 2015 were retrospectively reviewed. The prognostic significance of MVI was analyzed.

RESULTS: A total of 352 patients underwent pancreatectomy for invasive ductal carcinoma of the pancreas. A pathologic examination showed MVI in 228 (64.5%) of the patients. The median survival time (MST) was 21 months for the patients with MVI and 58 months for those without MVI (p < 0.001). A multivariate analysis showed the following to be significant prognostic factors: non-administration of adjuvant chemotherapy [hazard ratio (HR) 2.37; p < 0.001], lymph node metastasis (HR 2.95; p = 0.001), CA19-9 value of 300 U/ml or higher (HR 1.70; p = 0.018), and MVI (HR 1.84; p = 0.011). The overall survival was clearly stratified into three groups; favorable (MST not reached in stage 1 or 2A without MVI; p = 0.867), moderate (30 months in stage 2A with MVI and 30 months in stage 2B without MVI; p = 0.528), and poor (19 months in stage 2B with MVI and 17 months in stage 4; p = 0.322). The differences between these three groups all were significant.

CONCLUSIONS: Approximately two-thirds of patients with radiologically resectable pancreatic cancer had MVI and were considered to have potentially systemic disease. This study identified MVI as one of the significant factors for a poor prognosis and a valuable complement of tumor-node-metastasis staging.}, } @article {pmid29299933, year = {2018}, author = {Aydin, H and Guner, B and Esen Bostanci, I and Bulut, ZM and Aribas, BK and Dogan, L and Gulcelik, MA}, title = {Is there any relationship between adc values of diffusion-weighted imaging and the histopathological prognostic factors of invasive ductal carcinoma?.}, journal = {The British journal of radiology}, volume = {91}, number = {1084}, pages = {20170705}, pmid = {29299933}, issn = {1748-880X}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/therapy ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Gadolinium DTPA ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness/*diagnostic imaging/*pathology ; Neoplasm Staging ; Organometallic Compounds ; Prognosis ; Prospective Studies ; }, abstract = {OBJECTIVE: MRI is being used increasingly as a modality that can provide important information about breast cancer. Diffusion-weighted imaging (DWI) is an imaging technique from which apparent diffusion coefficient (ADC) values can be calculated in addition to obtaining important structural information which cannot be obtained from other imaging studies. We did not find any significant relationships between ADC values and prognostic factors, but did provide some explanations for conflicting results in the literature.

METHODS: The ADC results of 61 females with invasive ductal carcinomas were evaluated. DWI was performed and ADC values were calculated from the area in which restriction of diffusion was the highest in ADC mapping. B value was 500 and region of interest (ROI) was designated between 49 and 100 mm[2]. Calculations were performed automatically by the device. Tissue samples were obtained for prognostic factor evaluation. The relationships between ADC and prognostic factors were investigated. Comparisons between groups were made with one-way ANOVA and Kruskal Wallis test. Pairwise comparisons were made with Dunn's test. Analyses of categorical variables were made with Chi-square test.

RESULTS: We found a weak negative correlation between ADC and Ki-67 values (r = -0.279; p = 0.029). When we compared ADC values in regard to tumour type, we found no significant differences for tumour grade, Ki-67 positivity, estrogen receptor positivity, progesterone receptor positivity, C-erb B2, lymphovascular invasion and ductal carcinoma in situ or lobular carcinoma in situ component. On a side note, we found that mean ADC values decreased as tumour grade increased; however, this was not statistically significant.

CONCLUSION: The literature contains studies that report conflicting results which may be caused by differences in B values, ROI area and magnetic field strength. Multicentre studies and systematic reviews of these findings may produce crucial data for the use of DWI in breast cancer. Advances in knowledge: To determine if any significant relationship exists between DWI findings and prognostic factors of breast cancer.}, } @article {pmid29299000, year = {2017}, author = {Beach, JE and Ramsey, TD and Gorman, SK and Lau, TTY}, title = {Roles of Infectious Diseases Consultant Pharmacists and Antimicrobial Stewardship Pharmacists: A Survey of Canadian Tertiary Care Academic Hospitals.}, journal = {The Canadian journal of hospital pharmacy}, volume = {70}, number = {6}, pages = {415-422}, pmid = {29299000}, issn = {1920-2903}, abstract = {BACKGROUND: Infectious diseases consultant (IDC) pharmacists work within an IDC service to care for inpatients with complex infections. With Accreditation Canada's new Required Organizational Practice promoting the establishment of antimicrobial stewardship (AMS) programs, AMS pharmacists are being employed in acute care hospitals. There is potential for overlap in responsibilities between IDC and AMS pharmacists, but there is no literature outlining the current duties for each group in Canada.

OBJECTIVE: To describe the demographic characteristics and roles of IDC and AMS pharmacists in Canadian tertiary care academic hospitals.

METHODS: A survey of IDC and AMS pharmacists at Canadian tertiary care academic hospitals was conducted between February and April 2015. The questionnaire included questions about the pharmacist's experience, education, and training; the institution where the pharmacist was practising; the IDC or AMS team characteristics; and the pharmacist's roles in clinical, educational, administrative, and research sectors.

RESULTS: The survey response rate was 77% (68/88). The 68 respondents self-identified as IDC pharmacists (14 [21%]), AMS pharmacists (34 [50%]), or dual-role IDC and AMS pharmacists (20 [29%]). Compared with AMS pharmacists, IDC pharmacists reported more of the following unique clinical activities: directly communicating with patients, attending rounds, involving patients in decision-making, and providing patient education. The 3 groups of pharmacists described similar educational responsibilities. The AMS pharmacists performed more of the following administrative and research duties: development of antibiograms and preprinted orders, collection of antimicrobial metrics, and drug-use evaluations for antimicrobials. Dual-role IDC and AMS pharmacists were involved in fewer of the unique activities described by those who practised within a single subspecialty.

CONCLUSIONS: Self-identified IDC and AMS pharmacists in Canadian tertiary care academic hospitals were performing many similar roles; however, distinct differences within the clinical, administrative, and research domains were identified among IDC pharmacists, AMS pharmacists, and those who identified as dual-role IDC and AMS pharmacists.}, } @article {pmid29295717, year = {2018}, author = {Böttcher, R and Kweldam, CF and Livingstone, J and Lalonde, E and Yamaguchi, TN and Huang, V and Yousif, F and Fraser, M and Bristow, RG and van der Kwast, T and Boutros, PC and Jenster, G and van Leenders, GJLH}, title = {Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {8}, pmid = {29295717}, issn = {1471-2407}, support = {03O-402//Center for Translational Molecular Medicine/International ; #RS2014-01//Movember Foundation/International ; New Investigator Award//CIHR/Canada ; New Investigator Award//Terry Fox Research Institute/International ; }, mesh = {Adenocarcinoma/*genetics/pathology ; Aged ; Biomarkers, Tumor/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *DNA Copy Number Variations ; Follow-Up Studies ; *Genomic Instability ; Genomics/*methods ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA).

METHODS: Whole-slide images of The Cancer Genome Atlas Project (TCGA, N = 260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N = 199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC. Genomic instability was assessed by calculating the percentage of genome altered (PGA). Somatic copy number alterations (CNA) were determined using Fisher-Boschloo tests and logistic regression. Primary analysis were performed on TCGA (N = 260) as discovery and CPC-GENE (N = 199) as validation set.

RESULTS: CR/IDC growth was present in 80/260 (31%) TCGA and 76/199 (38%) CPC-GENE cases. Patients with CR/IDC and ≥ GS 7 had significantly higher PGA than men without this pattern in both TCGA (2.2 fold; p = 0.0003) and CPC-GENE (1.7 fold; p = 0.004) cohorts. CR/IDC growth was associated with deletions of 8p, 16q, 10q23, 13q22, 17p13, 21q22, and amplification of 8q24. CNAs comprised a total of 1299 gene deletions and 369 amplifications in the TCGA dataset, of which 474 and 328 events were independently validated, respectively. Several of the affected genes were known to be associated with aggressive prostate cancer such as loss of PTEN, CDH1, BCAR1 and gain of MYC. Point mutations in TP53, SPOP and FOXA1were also associated with CR/IDC, but occurred less frequently than CNAs.

CONCLUSIONS: CR/IDC growth is associated with increased genomic instability clustering to genetic regions involved in aggressive prostate cancer. Therefore, CR/IDC is a pathologic substrate for progressive molecular tumour derangement.}, } @article {pmid29291541, year = {2018}, author = {Garcia Hernandez, I and Canavati Marcos, M and Garza Montemayor, M and Lopez Sotomayor, D and Pineda Ochoa, D and Gomez Macias, GS}, title = {Her-2 positive mucinous carcinoma breast cancer, case report.}, journal = {International journal of surgery case reports}, volume = {42}, number = {}, pages = {242-246}, pmid = {29291541}, issn = {2210-2612}, abstract = {INTRODUCTION: Mucinous carcinoma is a variant of invasive breast carcinomas that accounts for 2% of them and has a better prognosis in contrast to the non-specific invasive carcinoma. They regularly are positive for estrogen and progesterone receptors and, generally, they do not overexpress HER2. When HER2 is positive, the first line treatment is trastuzumab; although the resistance is 52-89% for the non-specific carcinoma, it has been described just once in mucinous carcinoma.

CASE SUMMARY: A 48-year-old female presented with a lump in her right breast and after a biopsy, it was diagnosed as mucinous carcinoma in the core biopsy and surgical resection, with positive hormone receptors and HER2 positive (3+) in 100% of the tumor cells. She was treated with neoadjuvant chemotherapy based on trastuzumab and pertuzumab with no pathological response.

DISCUSSION: There are few pure mucinous carcinomas positive for HER2. Mucinous carcinomas are positive for HER2 account for less than 5% of invasive ductal carcinoma. Furthermore, our case was resistance to chemotherapy. Most mucinous carcinomas test negative for HER2, so they usually would not be treated with trastuzumab, in this case because the expression of HER2 in the biopsies we initiated it.

CONCLUSION: It's important to know that cases of mucinous carcinoma positive for HER2 exist and to be aware of the clinical problems that they may present: resistance to trastuzumab. Also, we need to understand the responsible mechanisms of this resistance and use immunohistochemistry for MUC which may predict it.}, } @article {pmid29290072, year = {2018}, author = {Kalisya, LM and Bake, JF and Bigabwa, R and Rothstein, DH and Cairo, SB}, title = {Operations for Suspected Neoplasms in a Resource-Limited Setting: Experience and Challenges in the Eastern Democratic of Congo.}, journal = {World journal of surgery}, volume = {42}, number = {7}, pages = {1913-1918}, pmid = {29290072}, issn = {1432-2323}, mesh = {Adult ; Child ; Democratic Republic of the Congo ; Female ; *Health Resources ; Humans ; Male ; Middle Aged ; Neoplasms/*surgery ; Retrospective Studies ; }, abstract = {INTRODUCTION: Surgery is an essential component of a functional health system, with surgical conditions accounting for nearly 11-15% of world disability. While communicable diseases continue to burden low- and low-middle-income countries, non-communicable diseases, such as cancer, are an important cause of morbidity and mortality worldwide. Preliminary data on malignancies in low- and middle-income countries, specifically in Africa, suggest a higher mortality compared to other regions of the world, a difference partially explained by limited availability of screening and early detection systems as well as poorer access to treatment.

OBJECTIVE: To evaluate the diagnosed tumor burden in the Eastern Democratic Republic of Congo (DRC) and review literature on existing and suspected barriers to accessing appropriate oncologic care.

METHODS: This is a retrospective study carried out at Healthcare, Education, community Action, and Leadership development Africa, a 197-bed tertiary referral hospital, in the Province of North Kivu, along the eastern border of the DRC from 2012 to 2015. Patient charts were reviewed for diagnoses of presumed malignancy with biopsy results.

RESULTS: A total of 252 cases of suspected cancer were reviewed during the study period; 39.7% were men. The average age of patients was 43 years. Amongst adult patients, the most common presenting condition involved breast lesions with 5.8% diagnosis of fibrocystic breast changes and 2.9% invasive ductal carcinoma of the breast. 37.3% of female patients had lesions involving the cervix or uterus. The most common diagnosis amongst male adults was prostate disease (16.7% of men). For pediatric patients, the most common diagnoses involved bone and/or cartilage (27.3%) followed by skin and soft tissue lesions (20.0%). All patients underwent surgical resection of lesions; some patients were advised to travel out of country for chemotherapy and radiation for which follow-up data are unavailable.

CONCLUSION: Adequate and timely treatment of malignancy in the DRC faces a multitude of challenges. Access to surgical services for diagnosis and management as well as chemotherapeutic agents is prohibitively limited. Increased collaboration with local clinicians and remote specialist consultants is needed to deliver subspecialty care in resource-poor settings.}, } @article {pmid29288666, year = {2018}, author = {Yu, P and Shen, X and Yang, W and Zhang, Y and Liu, C and Huang, T}, title = {ZEB1 stimulates breast cancer growth by up-regulating hTERT expression.}, journal = {Biochemical and biophysical research communications}, volume = {495}, number = {4}, pages = {2505-2511}, doi = {10.1016/j.bbrc.2017.12.139}, pmid = {29288666}, issn = {1090-2104}, mesh = {Breast Neoplasms/*metabolism/*pathology ; Cell Proliferation ; Cells, Cultured ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Telomerase/*metabolism ; Tumor Cells, Cultured ; Up-Regulation ; Zinc Finger E-box-Binding Homeobox 1/*metabolism ; }, abstract = {Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced. Finally, we verified that ZEB1, which mostly functions as a transcriptional repressor, can recruit the co-activator YAP to enhance the transcriptional activation of hTERT. Fascinatingly, instead of acting on E-boxes, the ZEB1/YAP complex tends to function as a transcriptional activator by binding with sequences potentially located in the hTERT promoter. Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.}, } @article {pmid29288333, year = {2018}, author = {Sourander, A and Chudal, R and Skokauskas, N and Al-Ansari, AM and Klomek, AB and Pornnoppadol, C and Kolaitis, G and Maezono, J and Steinhausen, HC and Slobodskaya, H and Kaneko, H and Regmee, J and Li, L and Nguyen, MH and Grimland, M and Osokina, O and Ong, SH and Praharaj, SK and Lesinskienė, S and Fossum, S and Wiguna, T and Makasheva, VA and Lehti, V}, title = {Unmet needs of child and adolescent psychiatrists among Asian and European countries: does the Human Development Index (HDI) count?.}, journal = {European child & adolescent psychiatry}, volume = {27}, number = {1}, pages = {5-8}, pmid = {29288333}, issn = {1435-165X}, } @article {pmid29286911, year = {2018}, author = {Lokanatha, D and Anand, A and Lakshmaiah, KC and Govind Babu, K and Jacob, LA and Suresh Babu, MC and Lokesh, KN and Rudresha, AH and Rajeev, LK and Saldanha, SC and Giri, GV and Koppaka, D and Kumar, RV}, title = {Primary breast angiosarcoma - a single institution experience from a tertiary cancer center in South India.}, journal = {Breast disease}, volume = {37}, number = {3}, pages = {133-138}, doi = {10.3233/BD-170291}, pmid = {29286911}, issn = {1558-1551}, mesh = {Adult ; Breast/*pathology/surgery ; *Breast Neoplasms/diagnosis/mortality/pathology/therapy ; Bridged-Ring Compounds/therapeutic use ; Chemotherapy, Adjuvant ; Dioxoles/therapeutic use ; Female ; *Hemangiosarcoma/diagnosis/mortality/pathology/therapy ; Humans ; India ; Middle Aged ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Taxoids/therapeutic use ; Tertiary Care Centers ; Tetrahydroisoquinolines/therapeutic use ; Trabectedin ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary angiosarcoma of the breast is a rare entity with incidence of less than 0.05% of all malignant breast neoplasms. It occurs in young females without any associated risk factors. The tumor behaves aggressively and has a poor prognosis compared to invasive ductal carcinoma.

METHOD: It was a retrospective observational study done at a tertiary cancer center from January 2012 to December 2016. The medical records of patients diagnosed with primary breast angiosarcoma were reviewed for the study. Clinicopathological profile, treatment, and the outcomes were analyzed.

RESULTS: Four patients were diagnosed with primary breast angiosarcoma out of 2560 breast cancer patients seen over a period of 5 years. Two had metastatic disease at presentation. Among four patients, two underwent surgery of the primary tumor, whereas, all received chemotherapy either as adjuvant or palliative setting. One patient received adjuvant radiation therapy. Three patients received 2nd line and one received 3rd line chemotherapy on disease progression. After a median follow-up of 18 months one patient was surviving on 3rd line chemotherapy with trabectedin. Other three succumbed to disease after progression.

CONCLUSION: Due to a small number of this malignancy randomized studies are difficult to perform and optimum treatment strategy still need to be defined.}, } @article {pmid29286468, year = {2017}, author = {Hidmark, AS and Nawroth, PP and Fleming, T}, title = {Analysis of Immune Cells in Single Sciatic Nerves and Dorsal Root Ganglion from a Single Mouse Using Flow Cytometry.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {130}, pages = {}, pmid = {29286468}, issn = {1940-087X}, mesh = {Animals ; Flow Cytometry/*methods ; Ganglia, Spinal/*cytology/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/*physiology ; Sciatic Nerve/*cytology/*immunology ; }, abstract = {Nerve-resident immune cells in the peripheral nervous system (PNS) are essential to maintaining neuronal integrity in a healthy nerve. The immune cells of the PNS are affected by injury and disease, affecting the nerve function and the capacity for regeneration. Neuronal immune cells are commonly analyzed by immunofluorescence (IF). While IF is essential for determining the location of the immune cells in the nerve, IF is only semi-quantitative and the method is limited to the number of markers that can be analyzed simultaneously and the degree of surface expression. In this study, flow cytometry was used for quantitative analysis of leukocyte infiltration into sciatic nerves or dorsal root ganglions (DRGs) of individual mice. Single cell analysis was performed using DAPI and several proteins were analyzed simultaneously for either surface or intracellular expression. Both sciatic nerves from one mouse that were treated according to this protocol generated ≥ 30,000 single nucleated events. The proportion of leukocytes in the sciatic nerves, determined by expression of CD45, was approximately 5% of total cell content in the sciatic nerve and approximately 5-10% in the DRG. Although this protocol focuses primarily on the immune cell population within the PNS, the flexibility of flow cytometry to measure a number of markers simultaneously means that the other cells populations present within the nerve, such as Schwann cells, pericytes, fibroblasts, and endothelial cells, can also be analyzed using this method. This method therefore provides a new means for studying systemic effects on the PNS, such as neurotoxicology and genetic models of neuropathy or in chronic diseases, such as diabetes.}, } @article {pmid29285517, year = {2017}, author = {Bejnordi, BE and Zuidhof, G and Balkenhol, M and Hermsen, M and Bult, P and van Ginneken, B and Karssemeijer, N and Litjens, G and van der Laak, J}, title = {Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images.}, journal = {Journal of medical imaging (Bellingham, Wash.)}, volume = {4}, number = {4}, pages = {044504}, pmid = {29285517}, issn = {2329-4302}, abstract = {Currently, histopathological tissue examination by a pathologist represents the gold standard for breast lesion diagnostics. Automated classification of histopathological whole-slide images (WSIs) is challenging owing to the wide range of appearances of benign lesions and the visual similarity of ductal carcinoma in-situ (DCIS) to invasive lesions at the cellular level. Consequently, analysis of tissue at high resolutions with a large contextual area is necessary. We present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, DCIS, and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of hematoxylin and eosin stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of nonmalignant and malignant slides and obtains a three-class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potential for routine diagnostics.}, } @article {pmid29285041, year = {2017}, author = {Yi, K and Min, KW and Wi, YC and Kim, Y and Shin, SJ and Chung, MS and Jang, K and Paik, SS}, title = {Wnt7a Deficiency Could Predict Worse Disease-Free and Overall Survival in Estrogen Receptor-Positive Breast Cancer.}, journal = {Journal of breast cancer}, volume = {20}, number = {4}, pages = {361-367}, pmid = {29285041}, issn = {1738-6756}, abstract = {PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis.

METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a.

RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99-7.80; p<0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80-46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11-165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29-17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression.

CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.}, } @article {pmid29285016, year = {2017}, author = {Zarei, F and Menbari, MN and Ghaderi, B and Abdi, M and Vahabzadeh, Z}, title = {Higher risk of progressing breast cancer in Kurdish population associated to CDH1 -160 C/A polymorphism.}, journal = {EXCLI journal}, volume = {16}, number = {}, pages = {1198-1205}, pmid = {29285016}, issn = {1611-2156}, abstract = {There is an increasing interest about studying possible effects of genetic polymorphisms and risk of cancer progression. E-cadherin (CDH1) involves in many important cellular processes including cell-cell interactions, cell development and genetic changes of this molecule has been associated with greater tumor metastasis. The present study was aimed to evaluate the possible role of CDH1 -160 C/A polymorphism as a potential risk factor for breast cancer in Kurdish population. This case-control study consisted of 100 breast cancer patients and 200 healthy controls. Clinicopathological findings of all individuals were reported and immunohistochemistry staining was carried out on tissue samples. The CDH1 -160 C/A genotype was determined by polymerase chain reaction- restriction fragment length polymorphism method (PCR-RFLP). CDH1 -160 C/A polymorphism was differently distributed between patient and control groups. The A allele of CDH1 -160 C/A polymorphism significantly increased in patients compared to controls. In addition we found that the A allele of this polymorphism might be a potential risk factor for progression of breast cancer in our studied population. Patients with A allele of CDH1 -160 C/A was in higher risk to progress invasive ductal carcinoma. The A allele was also correlated with high grade and stage IV and also with metastatic tumors in studied subjects. The CDH1 -160 C/A polymorphism is correlated with clinicopathologial findings of breast cancer patients. The A allele of CDH1 -160 C/A may be a risk factor for progression of breast cancer in Kurdish patients.}, } @article {pmid29284425, year = {2017}, author = {Holli-Helenius, K and Salminen, A and Rinta-Kiikka, I and Koskivuo, I and Brück, N and Boström, P and Parkkola, R}, title = {MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study.}, journal = {BMC medical imaging}, volume = {17}, number = {1}, pages = {69}, pmid = {29284425}, issn = {1471-2342}, mesh = {Breast Neoplasms/diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/*pathology ; Diagnosis, Differential ; Feasibility Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Neoplasm Grading ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: The aim of this study was to use texture analysis (TA) of breast magnetic resonance (MR) images to assist in differentiating estrogen receptor (ER) positive breast cancer molecular subtypes.

METHODS: Twenty-seven patients with histopathologically proven invasive ductal breast cancer were selected in preliminary study. Tumors were classified into molecular subtypes: luminal A (ER-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67 < 20 and low grade (I)) and luminal B (ER-positive and/or PR-positive, HER2-positive or HER2-negative with high Ki-67 ≥ 20 and higher grade (II or III)). Co-occurrence matrix -based texture features were extracted from each tumor on T1-weighted non fat saturated pre- and postcontrast MR images using TA software MaZda. Texture parameters and tumour volumes were correlated with tumour prognostic factors.

RESULTS: Textural differences were observed mainly in precontrast images. The two most discriminative texture parameters to differentiate luminal A and luminal B subtypes were sum entropy and sum variance (p = 0.003). The AUCs were 0.828 for sum entropy (p = 0.004), and 0.833 for sum variance (p = 0.003), and 0.878 for the model combining texture features sum entropy, sum variance (p = 0.001). In the LOOCV, the AUC for model combining features sum entropy and sum variance was 0.876. Sum entropy and sum variance showed positive correlation with higher Ki-67 index. Luminal B types were larger in volume and moderate correlation between larger tumour volume and higher Ki-67 index was also observed (r = 0.499, p = 0.008).

CONCLUSIONS: Texture features which measure randomness, heterogeneity or smoothness and homogeneity may either directly or indirectly reflect underlying growth patterns of breast tumours. TA and volumetric analysis may provide a way to evaluate the biologic aggressiveness of breast tumours and provide aid in decisions regarding therapeutic efficacy.}, } @article {pmid29281999, year = {2017}, author = {Mercogliano, MF and Inurrigarro, G and De Martino, M and Venturutti, L and Rivas, MA and Cordo-Russo, R and Proietti, CJ and Fernández, EA and Frahm, I and Barchuk, S and Allemand, DH and Figurelli, S and Deza, EG and Ares, S and Gercovich, FG and Cortese, E and Amasino, M and Guzmán, P and Roa, JC and Elizalde, PV and Schillaci, R}, title = {Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {895}, pmid = {29281999}, issn = {1471-2407}, support = {IDB/PICT 2012-382//Fondo para la Investigación Científica y Tecnológica/International ; PID 2012-066//Fondo para la Investigación Científica y Tecnológica/International ; IDB/PICT 2012-668//Fondo para la Investigación Científica y Tecnológica/International ; IDB/PICT 2012 1017//Fondo para la Investigación Científica y Tecnológica/International ; #20//Instituto Nacional del Cáncer (AR)/International ; 1819/03//Consejo Nacional de Investigaciones Científicas y Técnicas (AR)/International ; PIP 2012 059//Consejo Nacional de Investigaciones Científicas y Técnicas/International ; BOD/2016//Universidad Católica de Córdoba/International ; }, mesh = {Adult ; Aged ; Antineoplastic Agents, Immunological ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*mortality/pathology ; Carcinoma, Papillary/drug therapy/metabolism/*mortality/pathology ; Case-Control Studies ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Mucin-4/*metabolism ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/antagonists & inhibitors/immunology/*metabolism ; Retrospective Studies ; Survival Rate ; Trastuzumab/*pharmacology ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.

METHODS: We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry.

RESULTS: IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma.

CONCLUSION: In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.}, } @article {pmid29281592, year = {2018}, author = {Efrati, Y and Mikulincer, M}, title = {Individual-Based Compulsive Sexual Behavior Scale: Its Development and Importance in Examining Compulsive Sexual Behavior.}, journal = {Journal of sex & marital therapy}, volume = {44}, number = {3}, pages = {249-259}, doi = {10.1080/0092623X.2017.1405297}, pmid = {29281592}, issn = {1521-0715}, mesh = {Adult ; Compulsive Behavior/*diagnosis ; Factor Analysis, Statistical ; Humans ; Male ; Personality Inventory/statistics & numerical data ; *Self Report ; Sexual Behavior/*psychology ; Sexual Partners ; Surveys and Questionnaires/*standards ; }, abstract = {Compulsive sexual behavior comprises individual-based (e.g., sexual fantasies, compulsive sexual thoughts, masturbation) and partnered (e.g., interpersonal sexual conquests, repeated infidelity) facets. Most instruments for assessing compulsive sexual behavior, however, focus less on the individual-based facet and specifically on fantasies and compulsive thoughts. In the current research, we developed and validated an individual-based compulsive sexual behavior scale (I-CSB). In Study 1 (N = 492), the factorial structure of the I-CSB was examined. In Study 2 (N = 406), we assessed I-CSB's convergent validity. In Study 3 (N = 112), we examined whether the I-CSB differentiates between individuals who suffer from compulsive sexual behavior and those who do not. Results revealed a four-factor structure for individual-based compulsive sexual behavior that is associated with an intense inner conflict regarding sexuality (high arousal contrasting with high sexual anxiety), and that accounts for approximately 75% of the differences between people with compulsive sexual behavior and controls. Results are discussed in light of the need for a broader understanding of compulsive sexual behavior.}, } @article {pmid29281012, year = {2018}, author = {Perdijk, O and van Neerven, RJJ and Meijer, B and Savelkoul, HFJ and Brugman, S}, title = {Induction of human tolerogenic dendritic cells by 3'-sialyllactose via TLR4 is explained by LPS contamination.}, journal = {Glycobiology}, volume = {28}, number = {3}, pages = {126-130}, pmid = {29281012}, issn = {1460-2423}, mesh = {Animals ; Dendritic Cells/drug effects/*immunology ; Humans ; Immune Tolerance/drug effects/*immunology ; Lipopolysaccharides/*analysis/*immunology ; Milk, Human/chemistry ; NF-kappa B/metabolism ; Oligosaccharides/*immunology/pharmacology ; Toll-Like Receptor 4/immunology/*metabolism ; }, abstract = {The human milk oligosaccharide 3'-sialyllactose (3'SL) has previously been shown to activate murine dendritic cells (DC) in a Toll-like receptor (TLR) 4-mediated manner ex vivo. In this study we aimed to investigate whether 3'SL has similar immunomodulatory properties on human DC. 3'SL was shown to induce NF-κB activation via human TLR4. However, LPS was detected in the commercially obtained 3'SL from different suppliers. After the removal of LPS from 3'SL, we studied its ability to modify DC differentiation in vitro. In contrast to LPS and 3'SL, LPS-free 3'SL did not induce functional and phenotypical changes on immature DC (iDC). iDC that were differentiated in the presence of LPS or 3'SL showed a semi-mature phenotype (i.e., fewer CD83+CD86+ DC), produced IL-10 and abrogated IL-12p70 and tumor necrosis factor-alpha levels upon stimulation with several TLR ligands. Differentiation into these tolerogenic DC was completely abrogated by LPS removal from 3'SL. In contrast to previous reports in mice, we found that LPS-free 3'SL does not activate NF-κB via human TLR4. In conclusion, removing LPS from (oligo)saccharide preparations is necessary to study their potential immunomodulatory function.}, } @article {pmid29277603, year = {2018}, author = {Damti, Y and Gronau, I and Moran, S and Yavneh, I}, title = {Comparing evolutionary distances via adaptive distance functions.}, journal = {Journal of theoretical biology}, volume = {440}, number = {}, pages = {88-99}, doi = {10.1016/j.jtbi.2017.12.022}, pmid = {29277603}, issn = {1095-8541}, mesh = {*Algorithms ; Evolution, Molecular ; Likelihood Functions ; *Models, Genetic ; *Phylogeny ; *Sequence Alignment ; *Sequence Analysis, DNA ; Stochastic Processes ; }, abstract = {Distance-based methods for phylogenetic reconstruction are based on a two-step approach: first, pairwise distances are computed from DNA sequences associated with a given set of taxa, and then these distances are used to reconstruct the phylogenetic relationships between taxa. Because the estimated distances are based on finite sequences, they are inherently noisy, and this noise may result in reconstruction errors. Previous attempts to improve reconstruction accuracy focused either on improving the robustness of reconstruction algorithms to this stochastic noise, or on improving the accuracy of the distance estimates. Here, we aim to further improve reconstruction accuracy by utilizing the basic observation that reconstruction algorithms are based on a series of comparisons between distances (or linear combinations of distances). We start by examining the relationship between the stochastic noise in the sequence data and the accuracy of the comparisons between pairwise distance estimates. This examination results in improved methods for distance comparison, which are shown to be as accurate as likelihood-based methods, while being much simpler and more efficient to compute. We then extend these methods to improve reconstruction accuracy of quartet trees, and examine some of the challenges moving forward.}, } @article {pmid29277061, year = {2018}, author = {Sher-Censor, E and Shulman, C and Cohen, E}, title = {Associations among mothers' representations of their relationship with their toddlers, maternal parenting stress, and toddlers' internalizing and externalizing behaviors.}, journal = {Infant behavior & development}, volume = {50}, number = {}, pages = {132-139}, doi = {10.1016/j.infbeh.2017.12.005}, pmid = {29277061}, issn = {1934-8800}, mesh = {Adult ; Child Behavior Disorders/diagnosis/epidemiology/*psychology ; Child, Preschool ; Emotions/physiology ; Female ; Humans ; Infant ; Israel/epidemiology ; Male ; Mother-Child Relations/*psychology ; Mothers/psychology ; Parenting/*psychology ; Stress, Psychological/epidemiology/*psychology ; }, abstract = {This study examined the array of associations among the emotional valence and the coherence of mothers' representations of their relationship with their toddlers, mothers' reported parenting stress, and toddlers' internalizing and externalizing behaviors. To evaluate maternal representations, 55 mothers were interviewed using the Five Minute Speech Sample procedure (FMSS; Magaña et al., 1986), which was coded for criticism and positive comments (Magaňa-Amato, 1993), as well as coherence (Sher-Censor & Yates, 2015). Mothers also completed the Parenting Stress Index - Short Form (PSI; Abidin, 1997) to evaluate their parenting stress and the Child Behavior Checklist (CBCL/1.5-5; Achenbach & Rescorla, 2000) to assess their toddlers' internalizing and externalizing behaviors. Results indicated that parenting stress was associated with maternal criticism and fewer positive comments in the FMSS, but not with the coherence of mothers' FMSS. Parenting stress, criticism, and lower coherence in the FMSS were associated with maternal reports of externalizing behaviors. Only parenting stress and lower coherence in the FMSS were related to mothers' reports of internalizing behaviors of the child. Thus, the emotional valence and the coherence of mothers' representations of their relationship with their child and parenting stress may each constitute a distinct aspect of parenting and contribute to the understanding of individual differences in toddlers' internalizing and externalizing behaviors. Implications for research and practice with families of toddlers are discussed.}, } @article {pmid29276992, year = {2018}, author = {Levav, I and Klomek, AB}, title = {A review of epidemiologic studies on suicide before, during, and after the Holocaust.}, journal = {Psychiatry research}, volume = {261}, number = {}, pages = {35-39}, doi = {10.1016/j.psychres.2017.12.042}, pmid = {29276992}, issn = {1872-7123}, mesh = {Austria/epidemiology ; Concentration Camps/trends ; Epidemiologic Studies ; Germany/epidemiology ; Holocaust/*psychology/trends ; Humans ; Israel/epidemiology ; Jews/*psychology ; Suicide/*psychology/trends ; Survivors/psychology ; *World War II ; }, abstract = {The available literature on the risk of suicides related to the Holocaust (1939-1945) and its aftermath differs in its time periods, in the countries investigated, and in the robustness of its sources. Reliable information seems to indicate that the risk of suicide for Jews in Nazi Germany and Austria during the pre-war period (1933-1939) was elevated, while information on suicide during the internment in the concentration camps is fraught with problems. The latter derives from the Nazis' decision to hide the statistics on the inmates' causes of death, and from the prevailing life conditions that impeded separation between self-inflicted death and murder. Reliable studies conducted in Israel among refugees who entered pre-state Israel, 1939-1945, and post-World War II survivors reaching Israel (1948 on), show a mixed picture: suicide rates among the former were higher than comparison groups, while the latter group shows evidence of resilience.}, } @article {pmid29275106, year = {2018}, author = {Inoue, Y and Yamashita, N and Kitao, H and Tanaka, K and Saeki, H and Oki, E and Oda, Y and Tokunaga, E and Maehara, Y}, title = {Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer.}, journal = {Clinical breast cancer}, volume = {18}, number = {4}, pages = {e643-e650}, doi = {10.1016/j.clbc.2017.11.008}, pmid = {29275106}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Copy Number Variations ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Neoplasm Staging ; Prognosis ; Protein Phosphatase 2C/genetics/*metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved.

MATERIALS AND METHODS: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis.

RESULTS: The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types.

CONCLUSION: The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function.}, } @article {pmid29268186, year = {2018}, author = {Ishii, H and Chikamatsu, K and Igarashi, S and Takahashi, H and Sakamoto, K and Higuchi, H and Tanaka, S and Matsuoka, T and Masuyama, K}, title = {Establishment of Synergistic Chemoimmunotherapy for Head and Neck Cancer Using Peritumoral Immature Dendritic Cell Injections and Low-Dose Chemotherapies.}, journal = {Translational oncology}, volume = {11}, number = {1}, pages = {132-139}, pmid = {29268186}, issn = {1936-5233}, abstract = {The lack of available tumor antigens with strong immunogenicity, human leukocyte antigen restriction, and immunosuppression via regulatory T-cells (Tregs) and myeloid-derived suppressor cells are limitations for dendritic cell (DC)-based immunotherapy in patients with advanced head and neck cancer (HNC). We sought to overcome these limitations and induce effective antitumor immunity in the host. The effect of low-dose docetaxel (DTX) treatment on DC maturation was examined in an ex vivo study, and a phase I clinical trial of combination therapy with direct peritumoral immature DC (iDC) injection with OK-432 and low-dose cyclophosphamide (CTX) plus DTX was designed. Low-dose DTX did not negatively affect iDC viability and instead promoted maturation and IL-12 production. Five patients with metastatic or recurrent HNC were enrolled for the trial. All patients experienced grade 1 to 3 fevers. Intriguingly, elevated CD8+ effector T-cells and reduced Tregs were observed in four patients who completed two treatment cycles. All patients were judged to have progressive disease, but tumor regressions were observed in a subset of targeted metastatic lesions in two of five patients. Our results show that the combination of direct peritumoral iDC injection with OK-432 and low-dose CTX plus DTX is well tolerated and should give rise to changing the immune profile of T-cell subsets and improvement of immunosuppression in advanced HNC patients. Additionally, our ex vivo data on the effect of low-dose DTX treatment on DC maturation may contribute to developing new combination therapies with low-dose chemotherapy and immunotherapy.}, } @article {pmid29263698, year = {2017}, author = {Costarelli, L and Campagna, D and Ascarelli, A and Cavaliere, F and Colavito, MH and Ponzani, T and Broglia, L and La Pinta, M and Manna, E and Fortunato, L}, title = {Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?.}, journal = {Breast cancer (Dove Medical Press)}, volume = {9}, number = {}, pages = {581-586}, pmid = {29263698}, issn = {1179-1314}, abstract = {BACKGROUND: Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.

MATERIALS AND METHODS: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC) and 574 cases of high-grade invasive ductal carcinoma (HG-IDC). We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.

RESULTS: P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway), its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.

CONCLUSION: This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field.}, } @article {pmid29262562, year = {2017}, author = {Li, J and Sun, L and Xu, F and Xiao, J and Jiao, W and Qi, H and Shen, C and Shen, A}, title = {Characterization of plasma proteins in children of different Mycobacterium tuberculosis infection status using label-free quantitative proteomics.}, journal = {Oncotarget}, volume = {8}, number = {61}, pages = {103290-103301}, pmid = {29262562}, issn = {1949-2553}, abstract = {Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an infectious disease found worldwide. Children infected with MTB are more likely to progress to active TB (ATB); however, the molecular mechanism behind this process has long been a mystery. We employed the label-free quantitative proteomic technology to identify and characterize differences in plasma proteins between ATB and latent TB infection (LTBI) in children. To detect differences that are indicative of MTB infection, we first selected proteins whose expressions were markedly different between the ATB and LTBI groups and the control groups (inflammatory disease control (IDC) and healthy control (HC) groups). A total of 521 proteins differed (> 1.5-fold or < 0.6-fold) in the LTBI group, and 318 proteins in the ATB group when compared with the control groups. Of these, 49 overlapping proteins were differentially expressed between LTBI and ATB. Gene Ontology (GO) analysis revealed most proteins had a cellular and organelle distribution. The MTB infection status was mainly related to differences in binding, cellular and metabolic processes. XRCC4, PCF11, SEMA4A and ATP11A were selected and further verified by qPCR and western blot. At the mRNA level, the expression of XRCC4, PCF11and SEMA4A presented an increased trend in ATB group compare with LTBI. At the protein level, the expression of all these proteins by western blot in ATB/LTBI was consistent with the trends from proteomic detection. Our results provide important data for future mechanism studies and biomarker selection for MTB infection in children.}, } @article {pmid29256450, year = {2017}, author = {Mackeprang, PH and Vuong, D and Volken, W and Henzen, D and Schmidhalter, D and Malthaner, M and Mueller, S and Frei, D and Stampanoni, MFM and Dal Pra, A and Aebersold, DM and Fix, MK and Manser, P}, title = {Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy.}, journal = {Physics in medicine and biology}, volume = {63}, number = {1}, pages = {015015}, doi = {10.1088/1361-6560/aa97f8}, pmid = {29256450}, issn = {1361-6560}, mesh = {Algorithms ; Humans ; *Monte Carlo Method ; Neoplasms/*surgery ; *Phantoms, Imaging ; Radiometry ; Radiosurgery/*methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/*methods ; Radiotherapy, Intensity-Modulated/*methods ; }, abstract = {This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife[®] (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.}, } @article {pmid29249796, year = {2017}, author = {Farran, Y and Padilla, O and Chambers, K and Philipovskiy, A and Nahleh, Z}, title = {Atypical Presentation of Radiation-Associated Breast Angiosarcoma: A Case Report and Review of Literature.}, journal = {The American journal of case reports}, volume = {18}, number = {}, pages = {1347-1350}, pmid = {29249796}, issn = {1941-5923}, mesh = {Aged ; Breast Neoplasms/*etiology/pathology/radiotherapy ; Carcinoma, Ductal, Breast/radiotherapy ; Female ; Hemangiosarcoma/*etiology/pathology ; Humans ; *Neoplasms, Radiation-Induced ; Pigmentation Disorders/*etiology/pathology ; Radiotherapy, Adjuvant/*adverse effects ; }, abstract = {BACKGROUND Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence. CASE REPORT Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultrasounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences. CONCLUSIONS The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.}, } @article {pmid29246496, year = {2018}, author = {Hannafon, BN and Ding, WQ}, title = {miRNAs as Biomarkers for Predicting the Progression of Ductal Carcinoma in Situ.}, journal = {The American journal of pathology}, volume = {188}, number = {3}, pages = {542-549}, pmid = {29246496}, issn = {1525-2191}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; }, abstract = {Ductal carcinoma in situ (DCIS) is defined as a proliferation of neoplastic cells within the duct of the mammary gland that have not invaded into the surrounding stroma. DCIS is considered a precursor to invasive ductal carcinoma (IDC); however, approximately half of DCIS may progress to IDC, if left untreated. Current research has shown that the genomic and transcriptomic changes are present in DCIS before the emergence of invasive disease, indicating that the malignant nature of the DCIS is defined before invasion. However, important questions remain surrounding the specific changes and processes required for malignant progression and identification of prognostic indicators of aggressiveness. miRNAs are small regulatory RNAs that can modulate gene expression by complementary binding to target mRNAs and inducing translational repression and/or mRNA degradation. In the past decade, research has shown that miRNA expression is dysregulated in IDC and that these changes are already present at the DCIS stage. Therefore, changes in miRNA expression may provide the necessary information to identify a clinical indicator of the aggressiveness of DCIS. Herein, we review the miRNA signatures identified in DCIS, describe how these signatures may be used to predict the aggressiveness of DCIS, and discuss future perspectives for DCIS biomarker discovery.}, } @article {pmid29238033, year = {2017}, author = {Alkourbah, Y and Torabi, A and Ghaith, T and Nahleh, Z}, title = {Dermatopathic Lymphadenitis Mimicking Breast Cancer with Lymphatic Metastasis: A Case Report and Discussion.}, journal = {The American journal of case reports}, volume = {18}, number = {}, pages = {1330-1333}, pmid = {29238033}, issn = {1941-5923}, mesh = {Breast Neoplasms/diagnosis ; Diagnosis, Differential ; Eosinophils/pathology ; Female ; Humans ; Lymphadenitis/*diagnosis/pathology ; Lymphatic Metastasis/diagnosis ; Macrophages/pathology ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; }, abstract = {BACKGROUND Dermatopathic lymphadenitis is a rare benign lymphatic hyperplasia commonly associated with exfoliative or eczematoid dermatitis. Of interest, this condition can be confused with lymphatic metastasis in adults. CASE REPORT In this report, we describe the case of a 56-year-old woman diagnosed with left breast invasive ductal carcinoma in remission, who presented with dermatopathic lymphadenitis mimicking breast cancer recurrence. CONCLUSIONS Dermatopathic lymphadenitis is a benign entity that needs to be considered in the differential diagnosis of lymphadenopathy. Pursuing extensive workup in asymptomatic patients with a similar presentation and initial negative tests for malignancy recurrence is not recommended.}, } @article {pmid29231050, year = {2018}, author = {Moon, HJ and Kim, MJ and Yoon, JH and Kim, EK}, title = {Follow-up interval for probably benign breast lesions on screening ultrasound in women at average risk for breast cancer with dense breasts.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {59}, number = {9}, pages = {1045-1050}, doi = {10.1177/0284185117745906}, pmid = {29231050}, issn = {1600-0455}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; *Ultrasonography, Mammary ; }, abstract = {Background Women at high risk for breast cancer and women at average risk have different pretest probabilities. Probably benign lesions on screening ultrasound (US) should be assessed and managed differently for these two risk groups. Purpose To evaluate the effectiveness of short-term follow-up for probably benign lesions on screening US in women at average risk for breast cancer with dense breasts. Material and Methods A total of 445 women at average risk for breast cancer with probably benign lesions on screening US, dense breasts, and negative or benign mammography results were included. Women were classified into the six-month group (n = 345) or 12-month group (n = 100) according to when the first follow-up was performed (3-9 months or 9-15 months). The cancer detection rate, frequencies of newly developed lesions and progressed lesions, and biopsy rate were compared. Results There were no malignancies from three to 15 months. Three cancers newly developed after 15 months. One was a 3-mm ductal carcinoma in situ and two were 10-mm and 18-mm invasive ductal carcinoma without lymph node metastasis. The frequency of newly developed lesions and progressed lesions and biopsy rate were not significantly different between the six-month and 12-month groups (P = 0.320, 0.621, and >0.999). Conclusion A follow-up at 12 months can be considered for probably benign lesions on screening US in women at average risk for breast cancer with dense breasts. However, a large series prospective study is needed before clinical application.}, } @article {pmid29230302, year = {2017}, author = {Gharia, B and Seegobin, K and Maharaj, S and Marji, N and Deutch, A and Zuberi, L}, title = {Letrozole-induced hepatitis with autoimmune features: a rare adverse drug reaction with review of the relevant literature.}, journal = {Oxford medical case reports}, volume = {2017}, number = {11}, pages = {omx074}, pmid = {29230302}, issn = {2053-8855}, abstract = {While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis. After stopping letrozole, liver tests trended back to normal within 3 weeks. She scored 9 for Roussel-Uclaf Causality Assessment Method (RUCAM). Over the last 10 years, there have been reported cases of drug-induced hepatitis secondary to AIs. We anticipate that there will be more widespread use of AIs based on recommendations from the TEXT, SOFT and extended AI trials. Therefore, physicians must be aware of this rare but life-threatening complication.}, } @article {pmid29228910, year = {2017}, author = {Wu, Y and Zhang, N and Yang, Q}, title = {The prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in the breast: a meta-analysis.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {839}, pmid = {29228910}, issn = {1471-2407}, support = {No. 81672613//the National Natural Science Foundation of China/International ; No.2015GSF118093//Key Research and Development Program of Shandong Province/International ; No.2016GGE2775//Key Research and Development Program of Shandong Province/International ; No.2016CYJS01A02//Shandong Science and Technology Development Plan/International ; No. 81502285//the National Natural Science Foundation of China/International ; }, mesh = {*Breast Neoplasms/diagnosis/epidemiology/mortality/pathology ; *Carcinoma, Ductal, Breast/diagnosis/epidemiology/mortality/pathology ; *Carcinoma, Papillary/diagnosis/epidemiology/mortality/pathology ; Female ; Humans ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a rare variant of invasive ductal carcinoma (IDC). The prognosis of IMPC compared with that of IDC remains controversial; we conducted a meta-analysis to evaluate the prognostic difference between IMPC and IDC.

METHODS: We searched the PubMed, Cochrane Library, and EMBASE databases for relevant studies comparing overall survival (OS), disease-specific survival (DSS), relapse-free survival (RFS), local-regional recurrence-free survival (LRRFS) or distant metastasis-free survival (DMFS) rates between IMPC and IDC. Fixed-effect and random-effect models were utilized based on the heterogeneity of the eligible studies. Heterogeneity was further evaluated by subgroup and sensitivity analyses.

RESULTS: Fourteen studies with 1888 IMPC patients were included in the meta-analysis. The summarized odds ratio (OR) and 95% confidence interval (95% CI) was calculated to estimate the prognostic difference between IMPC and IDC. IMPC patients showed an unfavorable prognosis for RFS (OR; 2.04; 95% CI: 1.63-2.55) and LRRFS (OR: 2.82; 95% CI: 1.90-4.17) compared with IDC. However, no significant difference was observed in OS (OR: 0.93; 95% CI: 0.78-1.10), DSS (OR: 1.16; 95% CI: 0.95-1.40) and DMFS (OR: 0.95; 95% CI: 0.67-1.35) between IMPC and IDC. No obvious statistical heterogeneity was detected, except for DSS. Funnel plots and Egger's tests did not reveal publication bias, except for RFS.

CONCLUSIONS: This analysis showed that IMPC patients have a higher rate of loco-regional recurrence than IDC patients. However, OS, DSS and DMFS were not significantly different between IMPC and IDC. These results could help clinicians select therapeutic and follow-up strategies for IMPC patients.}, } @article {pmid29227474, year = {2018}, author = {Lehmann, LH and Jebessa, ZH and Kreusser, MM and Horsch, A and He, T and Kronlage, M and Dewenter, M and Sramek, V and Oehl, U and Krebs-Haupenthal, J and von der Lieth, AH and Schmidt, A and Sun, Q and Ritterhoff, J and Finke, D and Völkers, M and Jungmann, A and Sauer, SW and Thiel, C and Nickel, A and Kohlhaas, M and Schäfer, M and Sticht, C and Maack, C and Gretz, N and Wagner, M and El-Armouche, A and Maier, LS and Londoño, JEC and Meder, B and Freichel, M and Gröne, HJ and Most, P and Müller, OJ and Herzig, S and Furlong, EEM and Katus, HA and Backs, J}, title = {A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.}, journal = {Nature medicine}, volume = {24}, number = {1}, pages = {62-72}, pmid = {29227474}, issn = {1546-170X}, mesh = {Animals ; Epigenesis, Genetic ; Gene Transfer Techniques ; Heart Failure/genetics/*metabolism ; Hexosamines/*biosynthesis ; Histone Deacetylases/genetics/*metabolism ; Mice ; Mice, Knockout ; *Myocardial Contraction ; Myocardium/enzymology ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/metabolism ; Physical Conditioning, Animal ; Proteolysis ; Stromal Interaction Molecule 1/metabolism ; }, abstract = {The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.}, } @article {pmid29224275, year = {2017}, author = {Xu, XL and Tu, XY and Shui, RH and Cheng, YF and Yu, BH and Yang, WT}, title = {[Clinicopathologic study of infiltrating epitheliosis of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {46}, number = {12}, pages = {827-831}, doi = {10.3760/cma.j.issn.0529-5807.2017.12.003}, pmid = {29224275}, issn = {0529-5807}, mesh = {Biomarkers/metabolism ; Breast/metabolism/*pathology/ultrastructure ; Breast Neoplasms/pathology ; Carcinoma, Adenosquamous/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; China ; Diagnosis, Differential ; Epithelial Cells/metabolism/*pathology/ultrastructure ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/metabolism ; }, abstract = {Objective: To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods: Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer. Results: The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc. Conclusions: Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.}, } @article {pmid29223856, year = {2018}, author = {Wiedenmann, T and Dietrich, N and Fleming, T and Altamura, S and Deelman, LE and Henning, RH and Muckenthaler, MU and Nawroth, PP and Hammes, HP and Wagner, AH and Hecker, M}, title = {Modulation of glutathione peroxidase activity by age-dependent carbonylation in glomeruli of diabetic mice.}, journal = {Journal of diabetes and its complications}, volume = {32}, number = {2}, pages = {130-138}, doi = {10.1016/j.jdiacomp.2017.11.007}, pmid = {29223856}, issn = {1873-460X}, mesh = {Age Factors ; Aged ; Animals ; Case-Control Studies ; Cells, Cultured ; Diabetes Mellitus, Experimental/*metabolism/pathology ; Diabetic Nephropathies/metabolism/pathology ; Female ; Glutathione Peroxidase/*metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Kidney Glomerulus/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; Oxidative Stress/physiology ; Podocytes/*metabolism/pathology ; Protein Carbonylation/*physiology ; }, abstract = {AIMS: Low levels of reactive oxygen species and resulting oxidative protein modifications may play a beneficial role in cellular function under stress conditions. Here we studied the influence of age-dependent protein carbonylation on expression and activity of the anti-oxidative selenoenzyme glutathione peroxidase (GPx) in insulin-deficient Ins2[Akita] mice and type 2 diabetic obese db/db mice in context of diabetic nephropathy.

METHODS: Protein carbonylation, GPx expression and activity were examined in kidney tissue and lysates by common histological and protein biochemical methods.

RESULTS: In kidneys of Ins2[Akita] mice, carbonylated proteins, GPx-1 and GPx-4 expression were mainly detected in podocytes and mesangial cells. GPx activity was increased in kidney cortex homogenates of these mice. Remarkably, young animals did not show a concomitant increase in GPx expression but enhanced GPx carbonylation. No carbonylation-dependent modification of GPx activity was detected in db/db mice. In cultured podocytes hyperglycemia induced an increase in GPx expression but had no effect on activity or carbonylation. In kidney tissue sections of type 1 or type 2 diabetes patients, GPx-1 and GPx-4 expression but not overall protein carbonylation was significantly decreased.

CONCLUSIONS: These results indicate the existence of a threshold for beneficial carbonylation-dependent redox signaling during the progression of diabetic nephropathy.}, } @article {pmid29222933, year = {2018}, author = {Roth, G and Shahar, BH and Zohar-Shefer, Y and Benita, M and Moed, A and Bibi, U and Kanat-Maymon, Y and Ryan, RM}, title = {Benefits of emotional integration and costs of emotional distancing.}, journal = {Journal of personality}, volume = {86}, number = {6}, pages = {919-934}, doi = {10.1111/jopy.12366}, pmid = {29222933}, issn = {1467-6494}, support = {//Israel Science Foundation/International ; }, mesh = {Adult ; *Defense Mechanisms ; *Emotions ; Female ; Humans ; Male ; *Personal Autonomy ; *Self-Control ; Young Adult ; }, abstract = {OBJECTIVE: Three studies explored the consequences of the self-determination theory conception of integrative emotion regulation (IER; Ryan & Deci, 2017), which involves an interested stance toward emotions. Emotional, physiological, and cognitive consequences of IER were compared to the consequences of emotional distancing (ED), in relation to a fear-eliciting film.

METHOD: In Study 1, we manipulated emotion regulation by prompting students' (N = 90) IER and ED and also included a control group. Then we tested groups' defensive versus nondefensive emotional processing, coded from post-film written texts. Study 2 (N = 90) and Study 3 (N = 135) used the same emotion regulation manipulations but exposed participants to the fear-eliciting film twice, 72 hr apart, to examine each style's protection from adverse emotional, physiological, and cognitive costs at second exposure.

RESULTS: Participants who had been prompted to practice IER were expected to benefit more than participants in the ED and control groups at second exposure, as manifested in lower arousal and better cognitive capacity. Overall, results supported our hypotheses.

CONCLUSIONS: The current studies provide some support for the assumption that in comparison to ED, taking interest in and accepting one's negative emotions are linked with less defensive processing of negative experiences and with better functioning.}, } @article {pmid29217299, year = {2018}, author = {Zahorchak, AF and Macedo, C and Hamm, DE and Butterfield, LH and Metes, DM and Thomson, AW}, title = {High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.}, journal = {Cellular immunology}, volume = {323}, number = {}, pages = {9-18}, pmid = {29217299}, issn = {1090-2163}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R34 AI123033/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; }, mesh = {B7-2 Antigen/*immunology ; B7-H1 Antigen/*immunology ; Cell Differentiation/immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Interleukin-10/immunology ; Lymphocyte Activation ; Monocytes/immunology ; Organ Transplantation/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology ; }, abstract = {Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4[+] and CD8[+] T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8[+] T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway.}, } @article {pmid29215790, year = {2018}, author = {Carrascal, MA and Silva, M and Ramalho, JS and Pen, C and Martins, M and Pascoal, C and Amaral, C and Serrano, I and Oliveira, MJ and Sackstein, R and Videira, PA}, title = {Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.}, journal = {Molecular oncology}, volume = {12}, number = {5}, pages = {579-593}, pmid = {29215790}, issn = {1878-0261}, support = {P01 HL107146/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; E-Selectin/genetics/*metabolism ; Female ; Fucose/analogs & derivatives/pharmacology ; Fucosyltransferases/*antagonists & inhibitors ; Humans ; Ligands ; MAP Kinase Signaling System/drug effects ; Middle Aged ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Primary Cell Culture ; Sialyl Lewis X Antigen ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLe[X][/A]), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLe[X][/A] , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLe[X][/A] antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLe[X][/A] expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.}, } @article {pmid29212252, year = {2017}, author = {Shin, SY and Lee, DH and Lee, J and Choi, C and Kim, JY and Nam, JS and Lim, Y and Lee, YH}, title = {C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells.}, journal = {Oncotarget}, volume = {8}, number = {55}, pages = {94591-94605}, pmid = {29212252}, issn = {1949-2553}, abstract = {The CC motif chemokine receptor 1 (CCR1) has been implicated in tumor invasion and metastasis in numerous cancers. However, the detailed mechanism of CCR1 upregulation in metastatic tumor cells is poorly understood. The aim of this study was to clarify the regulatory mechanism underlying transcriptional activation of the CCR1 gene in response to epidermal growth factor (EGF) stimulation in breast cancer cells. CCR1 was highly expressed in human breast invasive ductal carcinoma (IDC) compared to adjacent normal tissues. Upon EGF stimulation, CCR1 expression was upregulated at the transcriptional level. Promoter analysis showed that signal transducer and activator of transcription 3 (STAT3) is necessary for EGF-induced CCR1 promoter activation, and STAT3 silencing abrogated EGF-induced CCR1 transcription. Pharmacological inhibition and short hairpin RNA-mediated knockdown experiments showed that AKT-dependent mammalian target of rapamycin (mTOR) activation was involved in the phosphorylation of serine-727 of STAT3, which in turn stimulated the transcription of the CCR1 gene. In conclusion, the AKT-mTOR-STAT3 signaling axis contributes to EGF-induced CCR1 expression, which promotes invasion and metastasis in breast cancer cells. We propose that the AKT-mTOR-STAT3 axis is a potential therapeutic target for blocking the invasion and metastasis of breast cancers.}, } @article {pmid29211399, year = {2018}, author = {Arribillaga, LC and Ledesma, M and Montedoro, A and Pisano, F and Bengió, RG}, title = {OAB score: a clinical model that predicts the probability of presenting overactive detrusor in the urodynamic study.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {44}, number = {2}, pages = {348-354}, pmid = {29211399}, issn = {1677-6119}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Urinary Bladder, Overactive/*diagnosis/physiopathology ; Urodynamics/*physiology ; }, abstract = {PURPOSE: To create a predictive model of involuntary detrusor contraction (IDC) to improve the diagnostic accuracy of overactive detrusor (OAD), associating overactive bladder (OAB) symptoms with other clinical parameters in the female population.

MATERIALS AND METHODS: A total of 727 women were studied retrospectively. In all of them, urodynamic study was conducted for urogynecological causes. Demographics information, personal history, symptoms, physical exam, a 3-day frequency/volume chart and urinary culture, were collected in all patients and they subsequently underwent uroflowmetry and urodynamic studies. A logistic regression model was performed in order to determine independent predictors of presence of IDC. Odd ratio (OR) estimation was used to assign a score to each one of the significant variables (p≤0.05) in the logistic regression model. We performed a ROC curve in order to determine the predictive ability of the score in relation to the presence of OAD.

RESULTS: presence of OAD was evident in 210 women (29%). In the logistic regression analysis, independent predictors of OAD were urgency, urgency incontinence, nocturia, absence of SUI symptoms, diabetes mellitus, reduction of vaginal trophism and bladder capacity below 150 mL. The probability of IDC diagnosis increases as the score raises (Score 0: 4% until Score ≥10: 88%). Sensitivity was 71% and specificity 72%. The area under the curve of OAB score was 0.784 (p>0.001).

CONCLUSIONS: OAB score is a clinical tool that shows higher diagnostic accuracy than OAB symptoms alone to predict overactive detrusor.}, } @article {pmid29209551, year = {2017}, author = {Yetkin, G and Celayir, F and Akgun, IE and Ucak, R}, title = {Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.}, journal = {Case reports in surgery}, volume = {2017}, number = {}, pages = {7048149}, pmid = {29209551}, issn = {2090-6900}, abstract = {A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.}, } @article {pmid29208716, year = {2017}, author = {Smith, LC and Yang, K and Pitcher, LH and Overstreet, BT and Chu, VW and Rennermalm, ÅK and Ryan, JC and Cooper, MG and Gleason, CJ and Tedesco, M and Jeyaratnam, J and van As, D and van den Broeke, MR and van de Berg, WJ and Noël, B and Langen, PL and Cullather, RI and Zhao, B and Willis, MJ and Hubbard, A and Box, JE and Jenner, BA and Behar, AE}, title = {Direct measurements of meltwater runoff on the Greenland ice sheet surface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {50}, pages = {E10622-E10631}, pmid = {29208716}, issn = {1091-6490}, abstract = {Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.1-km[2] moulin-terminating internally drained catchment (IDC) on Greenland's midelevation (1,207-1,381 m above sea level) ablation zone is compared with melt and runoff simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models. Current models cannot reproduce peak discharges or timing of runoff entering moulins but are improved using synthetic unit hydrograph (SUH) theory. Retroactive SUH applications to two older field studies reproduce their findings, signifying that remotely sensed IDC area, shape, and supraglacial river length are useful for predicting delays in peak runoff delivery to moulins. Applying SUH to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs suggests their terminal moulins receive lower peak discharges, less diurnal variability, and asynchronous runoff timing relative to climate/SMB model output alone. Conversely, large IDCs produce high moulin discharges, even at high elevations where melt rates are low. During this particular field experiment, models overestimated runoff by +21 to +58%, linked to overestimated surface ablation and possible meltwater retention in bare, porous, low-density ice. Direct measurements of ice surface runoff will improve climate/SMB models, and incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and subglacial systems.}, } @article {pmid29207971, year = {2017}, author = {Ko, H and Shin, J and Lee, JE and Nam, SJ and Nguyen, TL and Hopper, JL and Song, YM}, title = {Comparison of the association of mammographic density and clinical factors with ductal carcinoma in situ versus invasive ductal breast cancer in Korean women.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {821}, pmid = {29207971}, issn = {1471-2407}, support = {2014R1A2A2A01002705//the Basic Science Research Program through the National Research Foundation of Korea (NRF)/ ; }, mesh = {Adult ; Age of Onset ; Breast Density ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging ; Case-Control Studies ; Female ; Humans ; Mammography ; Menarche ; Middle Aged ; Parity ; Republic of Korea ; }, abstract = {BACKGROUND: In spite of the increasing incidence of in situ breast cancer, the information about the risk factors of in situ breast cancer (DCIS) is scarce as compared to the information available for invasive ductal breast cancer (IDC), with inconsistent findings regarding the difference in risk factors between DCIS and IDC.

METHODS: We enrolled 472 women with IDC and 90 women with DCIS and 1088 controls matching for age and menopausal status. Information on risk factors was collected through self-administered questionnaire. Percent mammographic dense area (PDA), absolute mammographic dense area (ADA), and nondense area were assessed using a computer-assisted thresholding technique. Odds ratio (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression model with adjustment for covariates.

RESULTS: Later age at menarche and regular physical exercise were associated with decreased risk of IDC, whereas alcohol consumption, previous benign breast disease, and family history of breast cancer were associated with increased risk of IDC. For DCIS, previous benign breast disease and alcohol consumption were associated with the increased risk, and regular physical exercise was associated with decreased risk. Increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.10 (95% CI: 1.01, 1.21) and 1.10 (95% CI: 1.01, 1.19) times greater risk of IDC, respectively. The increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.17 (95% CI: 0.91, 1.50) times and 1.11 (95% CI:0.90,1.37) times greater risk of DCIS, respectively, but the associations were not statistically significant. There was no significant difference in the association with risk factors and mammographic density measures between IDC and DCIS (P > 0.1).

CONCLUSIONS: Differential associations of DCIS with mammographic density and risk factors as compared with the associations of IDC were not evident. This finding suggests that IDC and DCIS develop through the shared causal pathways.}, } @article {pmid29206714, year = {2018}, author = {Khanlari, M and Schally, AV and Block, NL and Nadji, M}, title = {Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {26}, number = {1}, pages = {1-5}, doi = {10.1097/PAI.0000000000000622}, pmid = {29206714}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/*genetics ; *Drug Delivery Systems ; Female ; Humans ; Receptors, Neuropeptide/*genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/*genetics/metabolism ; Triple Negative Breast Neoplasms/*diagnosis/*genetics ; }, abstract = {PURPOSE: Growth hormone-releasing hormone (GHRH) has been shown to modify the growth behavior of many cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be effectively blocked by synthetic antagonists of its receptor and hence, the expression of GHRH-R by tumor cells could serve as a predictor of response to GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH-R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and immunophenotypically heterogenous, the staining results were also correlated with the histologic subtypes of these tumors.

MATERIALS AND METHODS: On the basis of histomorphology and immunophenotype, 134 cases of primary TNBCs were further subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were assessed semiquantitatively as negative, low expression, moderate, and high expression.

RESULTS: Of the 134 TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8 as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%) of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative for GHRH-R and, with the exception of 1 case with low expression, none of the metaplastic carcinomas expressed GHRH-R (P<0.005).

CONCLUSIONS: A considerable number of TNBCs are positive for GHRH-R as a predictor of potential response to anti-GHRH-R treatment. This expression however, varies considerably between histologic subtypes of triple-negative breast cancers. Although most medullary and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST show a positive reaction. Testing for GHRH-R expression is therefore advisable if anti-GHRH-R therapy is being considered.}, } @article {pmid29205352, year = {2018}, author = {Poirier, É and Desbiens, C and Poirier, B and Boudreau, D and Jacob, S and Lemieux, J and Doyle, C and Diorio, C and Hogue, JC and Provencher, L}, title = {Characteristics and long-term survival of patients diagnosed with pure tubular carcinoma of the breast.}, journal = {Journal of surgical oncology}, volume = {117}, number = {6}, pages = {1137-1143}, doi = {10.1002/jso.24944}, pmid = {29205352}, issn = {1096-9098}, mesh = {Adenocarcinoma/*mortality/pathology/surgery ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND AND OBJECTIVES: Pure tubular carcinomas (TC) of the breast are generally considered to have an excellent prognosis. This study aimed to analyze the characteristics and survival of patients with TC.

METHODS: This was a retrospective study conducted at the CHU de Québec-Université Laval. Databases were searched for all cases treated between April 1997 and December 2010. Survival was retrieved from the Province of Quebec Ministry of Health. Follow-up was censored on December 31, 2011. Overall survival (OS) was compared to patients with invasive ductal carcinoma (ICD) matched for age, tumor size, lymph node involvement, year of diagnosis, ER, PgR, and HER2, histological grade, lymphovascular invasion, and chemotherapy.

RESULTS: The frequency of TC was 2.9% (n = 223/7563). Tumors size was 7.4 ± 8.8 mm, without lymphovascular invasion (95.1%), ER-positive (98.2%), PgR-positive (69.5%), and HER2-negative (100%). Patients were followed up for 7.1 ± 2.7 years. The actuarial 13-year OS was 89.0% for TC, compared to 85.8% for IDC (P = 0.13). For TC, the 13-year OS was 95.8% in NO patients compared to 90.0% for N1-3 (P = 0.01).

CONCLUSION: Despite the general popular belief that patients with TC fare better than patients with IDC, the 13-year OS of TC was similar to that of grade I IDC.}, } @article {pmid29202609, year = {2018}, author = {Laenkholm, AV and Jensen, MB and Eriksen, JO and Buckingham, W and Ferree, S and Nielsen, TO and Ejlertsen, B}, title = {The ability of PAM50 risk of recurrence score to predict 10-year distant recurrence in hormone receptor-positive postmenopausal women with special histological subtypes.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {57}, number = {1}, pages = {44-50}, doi = {10.1080/0284186X.2017.1403044}, pmid = {29202609}, issn = {1651-226X}, mesh = {Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma/metabolism/pathology/therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Postmenopause ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Registries ; *Risk Assessment ; }, abstract = {INTRODUCTION: The Prosigna-PAM50 risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR) in hormone receptor-positive breast cancer. Here, we examine the ability of Prosigna for predicting DR at 10 years in a subgroup of postmenopausal breast cancer patients with special histological subtypes.

METHODS: Using the population based Danish Breast Cancer Group database, follow-up data were collected on all patients diagnosed from 2000 to 2003 with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2) normal breast cancer who by nationwide guidelines were treated with 5 year of endocrine therapy (N = 2558). Among patients with 1 to 3 positive lymph nodes or a tumor size >20 mm, we identified 1570 with invasive ductal carcinoma (IDC) and 89 with special histological subtypes (apocrine, medullary, mucinous, papillary, secretory, tubular, neuroendocrine) who were tested with Prosigna. Fine and Gray models were applied to determine the prognostic value of the Prosigna-PAM50 ROR score for DR special subtypes as compared to IDC.

RESULTS: Median follow-up for DR was 9.2 year and for OS 15.2 year. The 10-year DR rate for the special subtypes was 9.2% (95% CI: 4.0% to 17.2%) as compared to 13.7% (95% CI: 11.9% to 15.7%) for IDC. The 10-year OS was 74.2% (95% CI: 63.7% to 82.0%) for the special subtypes and 75.4% (95% CI: 73.2% to 77.4%) for IDC. Prosigna showed a statistical significant association of the continuous ROR score with risk of DR for both IDC and the special subtypes (IDC: p < .0001; special subtypes: p = .01).

CONCLUSION: In the present study, we demonstrated that Prosigna-PAM50 continuous ROR score added significant prognostic information for 10-year DR in postmenopausal patients with special subtypes (tumor size >20 mm or 1 to 3 positive lymph nodes) and ER-positive, HER2-normal early breast cancer.}, } @article {pmid29198152, year = {2018}, author = {Chudiwal, VS and Shahi, S and Chudiwal, S}, title = {Development of sustained release gastro-retentive tablet formulation of nicardipine hydrochloride using quality by design (QbD) approach.}, journal = {Drug development and industrial pharmacy}, volume = {44}, number = {5}, pages = {787-799}, doi = {10.1080/03639045.2017.1413111}, pmid = {29198152}, issn = {1520-5762}, mesh = {Chemistry, Pharmaceutical ; *Delayed-Action Preparations ; Drug Liberation ; Excipients/*chemistry ; Hypromellose Derivatives/*chemistry ; Nicardipine/*chemistry/*pharmacology ; Sodium Bicarbonate/*chemistry ; Tablets ; }, abstract = {The objective of the present study was to develop a sustained release gastro-retentive (SRGR) tablet formulation of nicardipine hydrochloride (HCl) for once-a-day dosing using the quality by design (QbD) approach. The quality target product profile of nicardipine HCl SRGR tablet formulation was defined, and critical quality attributes (CQAs) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tool and screened by the Plackett-Burman design, and finally nicardipine HCl SRGR tablet formulation was optimized using the Box-Behnken design. The tablets were prepared by a direct compression technique using polymers such as hydroxypropylmethylcellulose (HPMC K15M), glyceryl behenate, alone or in combinations and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of polymers and sodium bicarbonate on the drug release profile and floating properties were investigated as these parameters are likely to affect the desired once-a-day dosing regimen and finally the therapeutic efficacy of SRGR drug delivery systems. It was observed that formulation variables X1: Glyceryl behenate (mg/tab) and X2: HPMC K15M (mg/tab) strikingly influenced the drug release (%) (Y1), whereas floating lag time (min) (Y2) was significantly impacted by the formulation variable X3: Sodium bicarbonate (mg/tab). A design space plot within which the CQAs remained unchanged was established at a lab scale. In conclusion, this study demonstrated the suitability of a glyceryl behenate-HPMC K15M polymer combination along with sodium bicarbonate to achieve SRGR tablet formulation for once-a-day dosing of nicardipine HCl using the systematic QbD approach.}, } @article {pmid29196842, year = {2018}, author = {Shoshani, A and Kanat-Maymon, Y}, title = {Involvement in care in pediatric cancer patients: implications for treatment compliance, mental health and health-related quality of life.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {27}, number = {2}, pages = {567-575}, pmid = {29196842}, issn = {1573-2649}, mesh = {Child ; Female ; Humans ; Male ; Mental Health/*standards ; Neoplasms/pathology/psychology/*therapy ; Patient Compliance/*psychology ; Quality of Life/*psychology ; Surveys and Questionnaires ; }, abstract = {PURPOSE: The present study developed a new measure of involvement in care of pediatric oncology patients termed the Child Involvement in Care Scale (CICS), and empirically examined the mental health consequences of involvement in care for children with cancer.

METHOD: The CICS was administered to 236 children with cancer aged 8-12 who were recruited from three large hospitals in Israel. The children also completed questionnaires on their mental-health symptoms and emotional well-being. The children's parents completed measures on their child's compliance with treatment and health-related quality of life (HRQOL).

RESULTS: Exploratory and confirmatory factor analyses supported a 2-factor structure (knowledge and participation), representing different aspects of involvement in care. Compliance with treatment served as a mediator for the relationships between involvement in care and health-related outcomes. Involvement in care was positively associated with higher treatment compliance. In addition, treatment compliance was positively associated with HRQOL and positive emotions but negatively associated with psychiatric symptoms.

CONCLUSION: Pediatric cancer patients' involvement in the process of care is linked to better treatment compliance and mental health outcomes. Additional research is needed to examine the specific conditions and contexts in which involvement in care contributes to mental health and subjective well-being of children with cancer.}, } @article {pmid29195137, year = {2018}, author = {Rezende, F and Moll, F and Walter, M and Helfinger, V and Hahner, F and Janetzko, P and Ringel, C and Weigert, A and Fleming, I and Weissmann, N and Kuenne, C and Looso, M and Rieger, MA and Nawroth, P and Fleming, T and Brandes, RP and Schröder, K}, title = {The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.}, journal = {Redox biology}, volume = {15}, number = {}, pages = {12-21}, pmid = {29195137}, issn = {2213-2317}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Aorta/metabolism/pathology ; Diabetes Mellitus, Experimental/*genetics/metabolism/pathology ; Endothelial Cells/metabolism ; Gene Expression ; Humans ; Lymphocytes/metabolism/pathology ; Mice ; Mice, Knockout ; NADP/metabolism ; NADPH Oxidases/*genetics/metabolism ; Protein Binding ; Proteins/*genetics ; Reactive Oxygen Species/metabolism ; }, abstract = {AIM: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.

RESULTS: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.

INNOVATION AND CONCLUSION: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.}, } @article {pmid29191181, year = {2017}, author = {Sengal, AT and Haj-Mukhtar, NS and Elhaj, AM and Bedri, S and Kantelhardt, EJ and Mohamedani, AA}, title = {Immunohistochemistry defined subtypes of breast cancer in 678 Sudanese and Eritrean women; hospitals based case series.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {804}, pmid = {29191181}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Black People ; Breast Neoplasms/*classification/ethnology/metabolism ; Cohort Studies ; Eritrea ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Sudan ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy accounting for 25% of all cancers in females. In Africa, breast cancer prevalence and mortality are steadily increasing. Knowledge of hormone receptors and human epidermal growth factor receptor-2 (HER-2) expressions are vital for breast cancer management plans and decision making. There is wide regional variation in the proportion of these biomarkers, especially in African countries. Hormone receptors positivity in indigenous African and African American women is considered to be low and triple negative breast cancer is a dominant phenotype. There is paucity of data regarding hormone receptors (ER and PR) and HER2 expressions in North-eastern Africa (Eritrea and Sudan). The purpose of this study was to evaluate the expression of ER, PR and HER2 in Eritrean and Sudanese case series and correlate these biomarkers with the clinicopathological profile.

METHOD: Clinicopathologic data of patients were collected from clinical records. Immunohistochemistry biomarkers (ER, PR, and HER2) were assessed in consecutive female patients who had been diagnosed with invasive breast cancer from 2011 to 2015 in Gezira University Pathology Laboratory, the Sudan and National Health laboratory, Asmara, Eritrea.

RESULTS: There were 678 cases involved in this study. The mean age was 48.8 years with ±0.53 standard error of the mean. Two-thirds of the case were ≤50 years. Invasive ductal carcinoma, no special type was the most dominant histologic type (86%) in both study groups. The majority of cases (70%) had tumour stage pT2 and pT3 and about 50% had lymph node involvement. Less than 5% of the cases had well-differentiated tumours. The ER, PR and HER2 positive rates were 45%, 32%, and 29%, respectively. The proportion of luminal-A like, luminal-B like, HER2 enriched and TNBC were 37%, 13%, 16% and 34%, respectively. Fisher extract analysis showed age (p = .015), tumour size (p = .041), and histologic grade (p = .000) were significantly associated with intrinsic subtypes. Furthermore, Logistic regression analysis stratified by origin, age, tumour size, lymph-node metastasis and grade indicated that younger women age (≤50 years) and grade III tumours were more likely to be diagnosed with ER negative breast cancer.

CONCLUSION: Most of Sudanese and Eritrean women were diagnosed at younger age and with unfavourable prognostic clinicopathologic prognostic markers. TNBC is more frequent in this cohort study; patients with grade III tumours and young age are more likely to be hormone receptors negative. Therefore, routine determination of hormone receptors is warranted for appropriate targeted therapy.}, } @article {pmid29189723, year = {2017}, author = {Giroud, M and Scheideler, M}, title = {Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis.}, journal = {International journal of molecular sciences}, volume = {18}, number = {12}, pages = {}, pmid = {29189723}, issn = {1422-0067}, mesh = {Adipose Tissue/metabolism ; Animals ; Energy Metabolism/genetics/physiology ; Gene Expression Regulation ; Homeostasis ; Humans ; Muscle, Skeletal/metabolism ; Pancreas/metabolism ; RNA, Long Noncoding/genetics/*metabolism ; }, abstract = {Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization. lncRNAs are transcriptional regulators adding an additional regulatory layer in biological processes and pathophysiological conditions. Here, we review lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the substantial number of lncRNA loci in the human genome, the functionally characterized lncRNAs are just the tip of the iceberg. So far, our knowledge concerning lncRNAs in energy homeostasis is still in its infancy, meaning that the rest of the iceberg is a treasure chest yet to be discovered.}, } @article {pmid29183000, year = {2018}, author = {van Netten, JP and Cann, SH and Thornton, IG and Finegan, RP}, title = {The lymphatics in infiltrating ductal carcinoma (IDC) of the breast.}, journal = {Cancer treatment reviews}, volume = {62}, number = {}, pages = {97}, doi = {10.1016/j.ctrv.2017.10.015}, pmid = {29183000}, issn = {1532-1967}, mesh = {*Breast Neoplasms ; Carcinoma, Ductal ; Humans ; *Lymphatic Vessels ; }, } @article {pmid29181099, year = {2017}, author = {Guo, P and Pu, T and Chen, S and Qiu, Y and Zhong, X and Zheng, H and Chen, L and Bu, H and Ye, F}, title = {Breast cancers with EGFR and HER2 co-amplification favor distant metastasis and poor clinical outcome.}, journal = {Oncology letters}, volume = {14}, number = {6}, pages = {6562-6570}, pmid = {29181099}, issn = {1792-1074}, abstract = {ErbB signaling serves essential roles in invasive ductal carcinoma (IDC). The aim of the present study was to assess gene amplification in ErbB family members in IDC with clinical implications. Quantitative polymerase chain reaction and fluorescence in situ hybridization were performed on formalin-fixed paraffin-embedded tumor samples for gene amplification detection. The clinical and histopathological characteristics, as well as the prognostic significance, were analyzed. Among the 119 IDC patients evaluated, epidermal growth factor receptor [EGFR; also known as human epidermal growth factor receptor (HER)1], HER2, HER3 and HER4 gene amplification was observed in 30 (25.2%), 44 (36.9%), 0 (0.0%) and 1 (0.8%) patients, respectively. EGFR amplification was associated with estrogen receptor status (P=0.028) and higher possibilities of recurrence (P=0.015) and distant metastasis (following initial surgery) (P=0.011). In survival analysis, EGFR amplification was also associated with disease-free survival (DFS) (P=0.001) and overall survival (OS) (P=0.003). HER2 amplification was associated with larger tumor size (P=0.006), later clinical stage (P=0.003) and distant metastasis (following initial surgery) (P=0.006). In survival analysis, HER2 amplification was also associated with DFS (P=0.011). Notably, the present study identified a group of patients in whom EGFR and HER2 were co-amplified. This group of patients appeared to have a higher possibility of metastasis (when diagnosed) (P=0.014) and distant metastasis (following initial surgery) (P<0.001). In survival analysis, these patients were noticed to be associated with DFS (P<0.001) and OS (P=0.002). With respect to treatment regimen, this was also true for the DFS association with chemotherapy (P<0.001), radiotherapy (P<0.001) and hormonal therapy (P=0.001). The present results suggest that EGFR and HER2 amplification favor distant metastasis following initial surgery and are significantly associated with poor clinical outcome in breast cancer patients.}, } @article {pmid29181072, year = {2017}, author = {Badowska-Kozakiewicz, AM and Liszcz, A and Sobol, M and Patera, J}, title = {Retrospective evaluation of histopathological examinations in invasive ductal breast cancer of no special type: an analysis of 691 patients.}, journal = {Archives of medical science : AMS}, volume = {13}, number = {6}, pages = {1408-1415}, pmid = {29181072}, issn = {1734-1922}, abstract = {INTRODUCTION: Invasive ductal carcinoma (IDC) is the most common type of breast cancer in women and accounts for about 80% of all breast cancers.

MATERIAL AND METHODS: The material consisted of histological preparations derived from 691 patients treated for IDC-NST.

RESULTS: In our own study material, invasive ductal breast cancer of no special type accounted for more than 60% of cases, with the largest percentage of tumors being classified as G2 (53.96%) and G3 (28.98%). In terms of tumor size, the most common IDC-NST tumors were those of stage T1c (34.59%) and T2 (35.31%). The incidence of lymph node involvement was also assessed to reveal that no lymph node metastases were present in 45.44% of IDC-NST tumors. In the histopathological analysis of IDC-NST, significant statistical correlation was demonstrated between the presence of lymph node metastases and the histological malignancy grade (N0/G1-G3 p = 0.0103; N1A/G1-G3 p = 0.0498; N1B/G1-G3 p< 0.001; N3/G1-G3 p = 0.0027; N4/G1-G3 p < 0.001), between the presence of lymph node metastases and the tumor size (N0/T1-T4 p = 0.00295; N1B/T1-T4 p < 0.001; N2/T1-T4 p < 0.001; N2A/T1-T2 p < 0.001; N4/T1-T4 p < 0.001; Nx/T1-T4 p = 0.0447), as well as between the histological malignancy grade and the tumor size (G1/T1-T4 p < 0.001; G1/2/T1-T4 p < 0.001; G2/3/T1-T4 p < 0.0267).

CONCLUSIONS: Own research demonstrated that the most common histological type of breast cancer is invasive ductal carcinoma of no special type (IDC-NST); statistically significant correlations were demonstrated in IDC-NST patients between the lymph node involvement status and the histological malignancy grade or tumor size as well as between the histological malignancy grade and the tumor size.}, } @article {pmid29180760, year = {2017}, author = {Song, H and Sasada, S and Kadoya, T and Okada, M and Arihiro, K and Xiao, X and Kikkawa, T}, title = {Detectability of Breast Tumor by a Hand-held Impulse-Radar Detector: Performance Evaluation and Pilot Clinical Study.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {16353}, pmid = {29180760}, issn = {2045-2322}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; *Diagnostic Imaging/instrumentation/methods/standards ; Equipment Design ; Female ; Humans ; Pilot Projects ; *Radar/instrumentation ; Reproducibility of Results ; }, abstract = {In this report, a hand-held impulse-radar breast cancer detector is presented and the detectability of malignant breast tumors is demonstrated in the clinical test at Hiroshima University Hospital, Hiroshima, Japan. The core functional parts of the detector consist of 65-nm technology complementary metal-oxide-semiconductor (CMOS) integrated circuits covering the ultrawideband width from 3.1 to 10.6 GHz, which enable the generation and transmission of Gaussian monocycle pulse (GMP) with the pulse width of 160 ps and single port eight throw (SP8T) switching matrices for controlling the combination of 4 × 4 cross-shaped dome antenna array. The detector is designed to be placed on the breast with the patient in the supine position. The detectability of malignant tumors is confirmed in excised breast tissues after total mastectomy surgery. The three-dimensional positions of the tumors in the imaging results are consistent with the results of histopathology analysis. The clinical tests are conducted by a clinical doctor for five patients at the hospital. The malignant tumors include invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The final confocal imaging results are consistent with those of Magnetic Resonance Imaging (MRI), demonstrating the feasibility of the hand-held impulse-radar detector for malignant breast tumors.}, } @article {pmid29177598, year = {2018}, author = {Shimauchi-Ohtaki, H and Tosaka, M and Ohtani, T and Iijima, K and Sasaguchi, N and Kurihara, H and Yoshimoto, Y}, title = {Systemic metabolism and energy consumption after microsurgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage.}, journal = {Acta neurochirurgica}, volume = {160}, number = {2}, pages = {261-268}, doi = {10.1007/s00701-017-3400-0}, pmid = {29177598}, issn = {0942-0940}, mesh = {Aged ; Aneurysm, Ruptured/*surgery ; Calorimetry, Indirect ; Endovascular Procedures/*methods ; Energy Metabolism/*physiology ; Female ; Humans ; Intracranial Aneurysm/*surgery ; Male ; Microsurgery/*methods ; Middle Aged ; Neurosurgical Procedures/*methods ; Postoperative Period ; Subarachnoid Hemorrhage/*surgery ; Surgical Instruments ; }, abstract = {BACKGROUND: The postoperative metabolic states of subarachnoid hemorrhage (SAH) patients were investigated using indirect calorimetry (IDC) and various nutritional evaluations to establish any difference in perioperative metabolic and nutritional states between microsurgical and endovascular treatment.

METHODS: This study included 30 acute aneurysmal SAH patients with ruptured intracranial aneurysms treated by surgical clipping (n = 16) or coil embolization (n = 14) at a single institute. The resting energy expenditure (REE) and respiratory quotient were measured using IDC on days 1, 4, 7, 10, 14, and 17-21 after the operation. Various blood tests, including C-reactive protein (CRP) and prealbumin, were evaluated on the same days.

RESULTS: The clipping group showed a significant increase in REE/basal energy expenditure (BEE) compared with the coiling group on days 1 and 4 (p = 0.04 and 0.03, respectively). No significant differences were found on days 7, 10, 14, and 17-21. The mean REE/BEE on days 1-14 and 1-21 showed no significant differences between the groups with repeated measures analysis of variance. The clipping group showed a significant decrease of prealbumin on day 4 and significant increase in CRP on days 1, 4, and 7.

CONCLUSIONS: The clipping group was in the hypermetabolic state compared with the coiling group during the very early postoperative period. However, the difference associated with the treatment modality was relatively small compared to the effects of the SAH and of the sequelae.}, } @article {pmid29174251, year = {2017}, author = {Dalal, J and Katekhaye, V and Jain, R}, title = {Effect of ferric carboxymaltose on hospitalization and mortality outcomes in chronic heart failure: A meta-analysis.}, journal = {Indian heart journal}, volume = {69}, number = {6}, pages = {736-741}, pmid = {29174251}, issn = {2213-3763}, mesh = {*Anemia, Iron-Deficiency/drug therapy/etiology/mortality ; Ferric Compounds/*administration & dosage ; Global Health ; *Heart Failure/complications/mortality/therapy ; Hospitalization/*trends ; Humans ; Infusions, Intravenous ; Maltose/administration & dosage/*analogs & derivatives ; Prospective Studies ; *Quality of Life ; }, abstract = {INTRODUCTION: Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure (CHF). Our aim was to assess effect of ferric carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF.

MATERIALS AND METHODS: A literature search across PUBMED, Google Scholar and trials database www.clinicaltrials.gov was conducted to search for randomized controlled trials (till August 2016) comparing FCM to placebo in CHF with or without anaemia. Published human studies in English language which reported data on mortality and hospitalization rates were included. Primary outcome was rates of HF hospitalizations and secondary outcomes were hospitalization due to any cardiovascular (CV) cause, death due to worsening HF and any CV death.

RESULTS: From 17 studies identified, two were included in final analysis (n=760; 455 in FCM and 305 in placebo arms). We observed significantly lower rates of hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence interval (CI) 0.19, 0.59, p=0.0001] as well as for any CV hospitalizations [RR 0.49, 95% CI 0.35, 0.70; p<0.0001] (figure). No heterogeneity in studies was seen for these two outcomes (I[2]=0%, p>0.05). No significant treatment effect with FCM was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p=0.55) or any CV death (RR 0.80, 95% CI 0.40, 1.57; p=0.51).

CONCLUSION: FCM reduces hospitalization rates in CHF but may not reduce mortality outcome. This finding needs further evaluation in a large, prospective, randomized controlled trial.}, } @article {pmid29172285, year = {2017}, author = {Chaveepojnkamjorn, W and Thotong, R and Sativipawee, P and Pitikultang, S}, title = {Body Mass Index and Breast Cancer Risk among Thai Premenopausal Women: a Case-Control Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {11}, pages = {3097-3101}, pmid = {29172285}, issn = {2476-762X}, abstract = {Background: Breast cancer (BC) is the leading malignancy in women with high incidence and mortality worldwide. Obesity is one of several established risk factors for chronic diseases including cancer. The objective of this research was to determine the association of body mass index (BMI) with BC among Thai premenopausal women (TPW). Materials and Methods: A case-control study was conducted among TPW attending the National Cancer Institute in Bangkok, with 257 cases and 257 controls in 2013-2014. Cases and controls were matched by age (± 5 years), residential area and duration of attending. Data were collected with a questionnaire comprising 2 parts: part 1 socio-demographic characteristics, and part 2 health risk behavior and reproductive factors and BMI. The obtained data were analyzed using descriptive and analytic statistics with a computerized statistical package. Results: The study participants were mainly 40-44 years old (60 %) with an average age of 39 years. The major type of BC was the invasive ductal carcinoma (91.8%). On univariate analysis, risk factors for BC among the TPW were family history of BC, history of benign breast tumors, younger age at menarche, parity, miscarriage, contraceptive use, passive smoking, multivitamin use, and BMI (p<0.05). Multivariable conditional logistic regression analysis, controlling for possible confounding factors, revealed that a BMI 25-29.9 and ≥ 30 kg/m2 increased the risk of BC by a factor of 2.09 and 2.37 times, respectively (OR=2.09, 95%CI =1.09-3.97; OR=2.37, 95%CI =1.24-10.06). Conclusions: A surveillance system of obesity should be conducted in cooperation with information regarding physical activities and weight control among TPW as an essential measure to reduce BC risk.}, } @article {pmid29172216, year = {2018}, author = {Deprez, PH and Garces Duran, R and Moreels, T and Furneri, G and Demma, F and Verbeke, L and Van der Merwe, SW and Laleman, W}, title = {The economic impact of using single-operator cholangioscopy for the treatment of difficult bile duct stones and diagnosis of indeterminate bile duct strictures.}, journal = {Endoscopy}, volume = {50}, number = {2}, pages = {109-118}, doi = {10.1055/s-0043-121268}, pmid = {29172216}, issn = {1438-8812}, mesh = {Adult ; Aged ; Cholangiopancreatography, Endoscopic Retrograde/*economics/methods ; Cholestasis/diagnosis/etiology/*surgery ; Cost-Benefit Analysis ; Female ; Follow-Up Studies ; Gallstones/complications/diagnosis/*surgery ; Humans ; Male ; Middle Aged ; *Models, Economic ; Retrospective Studies ; Severity of Illness Index ; }, abstract = {BACKGROUND AND STUDY AIM: Conventional endoscopic retrograde cholangiopancreatography (ERCP) combines endoscopy and radiography to diagnose and treat pathological conditions of the bile duct. The aim of the present analysis was to evaluate the clinical and economic impact of the use of single-operator intraductal cholangioscopy (IDC), which allows for direct visualization of the bile duct, as an alternative to ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures.

PATIENTS AND METHODS: The clinical and economic consequences of single-operator IDC use were evaluated using two decision-tree models, one for management of difficult-to-remove stones and one for stricture diagnosis. A hospital perspective was adopted. Data to populate the models were derived from two Belgian hospitals that specialize in endoscopic procedures of the bile duct. Overall, the examined population consisted of 62 patients with difficult stones and 49 patients with indeterminate strictures.

RESULTS: In the model for difficult stone management, the use of IDC determined a decrease in the number of procedures (- 27 % relative reduction) and costs (- €73 000; - 11 % relative reduction) when compared with ERCP. In the model for stricture diagnosis, the use of IDC determined a decrease in the number of procedures (- 31 % relative reduction) and costs (- €13 000; - 5 % relative variation) when compared with ERCP.

CONCLUSIONS: The single-operator IDC system performed better than ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures, and reduced the overall expenditure in hospitals in Belgium.}, } @article {pmid29164828, year = {2019}, author = {Koren, D and Rothschild-Yakar, L and Lacoua, L and Brunstein-Klomek, A and Zelezniak, A and Parnas, J and Shahar, G}, title = {Attenuated psychosis and basic self-disturbance as risk factors for depression and suicidal ideation/behaviour in community-dwelling adolescents.}, journal = {Early intervention in psychiatry}, volume = {13}, number = {3}, pages = {532-538}, doi = {10.1111/eip.12516}, pmid = {29164828}, issn = {1751-7893}, support = {//University of Haifa/International ; //Israel Science Foundation/International ; }, mesh = {Adolescent ; Depressive Disorder/*diagnosis/psychology ; Depressive Disorder, Major/diagnosis/psychology ; *Ego ; Female ; Humans ; Independent Living/psychology ; Male ; Pilot Projects ; Prodromal Symptoms ; Psychotic Disorders/*diagnosis/psychology ; Risk Factors ; Self-Injurious Behavior/diagnosis/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND AND AIMS: Adolescents at clinical high risk (CHR) for psychosis, as defined by the presence of attenuated psychosis symptoms (APS), exhibit increased levels of suicidal ideation and behaviour. However, no research thus far has examined the link between basic self-disturbances (SDs), an established marker for CHR, and suicidality/self-harm in this population. The goal of this pilot study was to assess the association between SD, depression and suicidal ideation and behaviour among non-help-seeking adolescents from the community.

METHOD: A total of 100 community-dwelling adolescents (age range: 13-16) were assessed using the Examination of Anomalous Self-experience, Prodromal Questionnaire, Structured Interview for Prodromal Syndromes, Mood and Anxiety Symptom Questionnaire and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The K-SADS was used to derive a binary diagnosis of unipolar depression, as well as to measure suicidal ideation and behaviour and self-harm.

RESULTS: In a multiple regression analysis, SD accounted for variance in depressive symptoms and suicidality/self-harm over and above that accounted for by APS. Moreover, SD accounted for variance in suicidality/self-harm over and above that accounted for by depression symptoms.

CONCLUSIONS: These pilot results suggest that SD might be a unique dimension of vulnerability to depression and suicidality/self-harm in adolescence. Also, they encourage assessment of SD as part of a suicide risk assessment, particularly in the context of risk for subsequent psychosis.}, } @article {pmid29163938, year = {2017}, author = {, and Baqui, AH and Khanam, R and Rahman, MS and Ahmed, A and Rahman, HH and Moin, MI and Ahmed, S and Jehan, F and Nisar, I and Hussain, A and Ilyas, M and Hotwani, A and Sajid, M and Qureshi, S and Zaidi, A and Sazawal, S and Ali, SM and Deb, S and Juma, MH and Dhingra, U and Dutta, A and Ame, SM and Hayward, C and Rudan, I and Zangenberg, M and Russell, D and Yoshida, S and Polašek, O and Manu, A and Bahl, R}, title = {Understanding biological mechanisms underlying adverse birth outcomes in developing countries: protocol for a prospective cohort (AMANHI bio-banking) study.}, journal = {Journal of global health}, volume = {7}, number = {2}, pages = {021202}, pmid = {29163938}, issn = {2047-2986}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Biological Specimen Banks/*organization & administration ; *Biomarkers ; *Developing Countries ; Feasibility Studies ; Female ; Humans ; Pregnancy ; *Pregnancy Outcome ; Prospective Studies ; }, abstract = {OBJECTIVES: The AMANHI study aims to seek for biomarkers as predictors of important pregnancy-related outcomes, and establish a biobank in developing countries for future research as new methods and technologies become available.

METHODS: AMANHI is using harmonised protocols to enrol 3000 women in early pregnancies (8-19 weeks of gestation) for population-based follow-up in pregnancy up to 42 days postpartum in Bangladesh, Pakistan and Tanzania, with collection taking place between August 2014 and June 2016. Urine pregnancy tests will be used to confirm reported or suspected pregnancies for screening ultrasound by trained sonographers to accurately date the pregnancy. Trained study field workers will collect very detailed phenotypic and epidemiological data from the pregnant woman and her family at scheduled home visits during pregnancy (enrolment, 24-28 weeks, 32-36 weeks & 38+ weeks) and postpartum (days 0-6 or 42-60). Trained phlebotomists will collect maternal and umbilical blood samples, centrifuge and obtain aliquots of serum, plasma and the buffy coat for storage. They will also measure HbA1C and collect a dried spot sample of whole blood. Maternal urine samples will also be collected and stored, alongside placenta, umbilical cord tissue and membrane samples, which will both be frozen and prepared for histology examination. Maternal and newborn stool (for microbiota) as well as paternal and newborn saliva samples (for DNA extraction) will also be collected. All samples will be stored at -80°C in the biobank in each of the three sites. These samples will be linked to numerous epidemiological and phenotypic data with unique study identification numbers.

IMPORTANCE OF THE STUDY: AMANHI biobank proves that biobanking is feasible to implement in LMICs, but recognises that biobank creation is only the first step in addressing current global challenges.}, } @article {pmid29156701, year = {2017}, author = {Lopes-Bastos, B and Jin, L and Ruge, F and Owen, S and Sanders, A and Cogle, C and Chester, J and Jiang, WG and Cai, J}, title = {Association of breast carcinoma growth with a non-canonical axis of IFNγ/IDO1/TSP1.}, journal = {Oncotarget}, volume = {8}, number = {49}, pages = {85024-85039}, pmid = {29156701}, issn = {1949-2553}, abstract = {Reciprocal interactions between cancers and the surrounding microenvironment have an important role in tumour evolution. In this study, our data suggested that through thrombospondin 1 (TSP1), tumour-associated microvessel provides a dormant niche to sustain inactive status of breast invasive ductal carcinoma (IDC) cells. TSP1 levels in the tumour stroma were negatively correlated with vascular indoleamine 2,3-dioxygenase 1 (IDO1) in IDC tissues. IDO1 is an intracellular enzyme initiating the first and rate-limited step of tryptophan breakdown. Lower stromal TSP1 levels and positive tumour vascular IDO1 staining seems to associate with poor survive of patients with IDC. IDC cells induced a significantly increase in IDO1 expression in endothelial cells (ECs). IFNγ exerts a similar effect on ECs. We hypothesized a tryptophan starvation theory that since tryptophan is essential for the synthesis of TSP1, IDO1 induce a decrease in tryptophan availability and a reduction in TSP1 synthesis in ECs, leading to overcoming the dormancy state of IDC cells and exacerbating conditions such as tumour invasion and metastasis. These findings identify a non-canonical role of IFNγ/IDO1/TSP1 axis in microvascular niche-dominated dormancy of breast invasive ductal carcinoma with a solid foundation for further investigation of therapeutic and prognostic relevance.}, } @article {pmid29155474, year = {2018}, author = {Gilboa, Y and Frenkel, TI and Schlesinger, Y and Rousseau, S and Hamiel, D and Achiron, R and Perlman, S}, title = {Visual biofeedback using transperineal ultrasound in second stage of labor.}, journal = {Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology}, volume = {52}, number = {1}, pages = {91-96}, doi = {10.1002/uog.18962}, pmid = {29155474}, issn = {1469-0705}, mesh = {Adult ; *Biofeedback, Psychology ; Delivery, Obstetric/*methods ; Female ; Head/*diagnostic imaging/embryology ; Humans ; Infant, Newborn ; Labor Stage, Second/*physiology ; Perineum/*diagnostic imaging ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Self Report ; *Ultrasonography/methods ; }, abstract = {OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor.

METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives.

RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P = 0.01), as indicated by a significantly lower delta AoP before (mean, 22.2° (95% CI, 13.9-31.7°)) compared with after (mean, 35.2° (95% CI, 25.9-45.3°)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P = 0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P = 0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups.

CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.}, } @article {pmid29154888, year = {2017}, author = {Hou, N and Wen, Y and Yuan, X and Xu, H and Wang, X and Li, F and Ye, B}, title = {Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {103}, number = {3}, pages = {267-275}, pmid = {29154888}, issn = {1096-0945}, support = {R01 HL072166/HL/NHLBI NIH HHS/United States ; R01 HL111480/HL/NHLBI NIH HHS/United States ; R01 HL122793/HL/NHLBI NIH HHS/United States ; }, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Cardiomyopathies/genetics/pathology ; Cardiomyopathy, Dilated/*genetics/pathology ; DNA-Binding Proteins/*genetics ; Humans ; Mice ; Muscular Dystrophies/genetics/pathology ; Myocardial Ischemia/*genetics/pathology ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Signal Transduction/genetics ; TEA Domain Transcription Factors ; Transcription Factors/*genetics ; YAP-Signaling Proteins ; }, abstract = {Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES). Our results demonstrated that Yap1, Taz, and Tead1 were significantly increased in failing human and DES hearts compared with the non-failing controls (NFH) or wild type (WT) mouse hearts at both mRNA and protein levels. Interestingly, adult human and mouse hearts had more Taz than Yap1 by mRNA and protein expression and their increases in diseased hearts were proportional and did not change Yap1/Taz ratio. Yap1, Taz, and Tead1 were accumulated in the nuclear fraction and cardiomyocyte nuclei of diseased hearts. The ratio of Yap1 phosphorylated at serine 127 (human) or serine 112 (mouse) to the total Yap1 (pYap1/Yap1) was significantly lower in the nuclear fraction of diseased hearts than that in normal controls. More importantly, Hippo downstream targets Ankrd1, Ctgf, and Cyr61 were transcriptionally elevated in the diseased hearts. These results suggest that Yap1/Taz signaling is activated in human and mouse dysfunctional hearts. Further investigation with relevant animal models will determine whether this pathway is a potential target for preventing and reversing abnormal remodeling during the progression of different cardiac disorders.}, } @article {pmid29150851, year = {2018}, author = {McDonald, M and Brindley, S and Halperin, E and Saguy, T}, title = {Outgroup members' internal criticism promotes intergroup openness: The role of perceived risk.}, journal = {The British journal of social psychology}, volume = {57}, number = {1}, pages = {95-111}, doi = {10.1111/bjso.12231}, pmid = {29150851}, issn = {2044-8309}, mesh = {Adult ; Female ; *Group Processes ; *Hostility ; Humans ; Israel ; Male ; Middle Aged ; Risk ; *Social Behavior ; *Social Perception ; Young Adult ; }, abstract = {Research suggests that hearing an outgroup member voice internal criticism increases individuals' openness to the outgroup's perspective. We replicate and extend these findings in the context of the Israeli-Palestinian conflict. Israeli participants exposed to a Palestinian official voicing internal criticism reported more openness to the Palestinian narrative of the conflict, an effect that was mediated by an increase in participants' perception that Palestinians are open-minded and a subsequent increase in their hope for more positive relations between the two groups. In our extension of these findings, we examined a complementary mechanism contributing to the effectiveness of the criticism manipulation, specifically the extent to which participants perceive that the Palestinian official took a risk voicing criticism of Palestinians. Positive messages from a hostile outgroup may be received with suspicion, but if they are articulated under great risk to the speaker, greater credibility may be granted. Across two studies, we demonstrate that the criticism conveys risk to the speaker and that this risk is predictive of the perceived credibility of the speaker, and participants' subsequent openness to the outgroup's perspective.}, } @article {pmid29146271, year = {2018}, author = {Co, M and Kwong, A and Shek, T}, title = {Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature.}, journal = {International journal of surgery (London, England)}, volume = {49}, number = {}, pages = {27-31}, doi = {10.1016/j.ijsu.2017.11.005}, pmid = {29146271}, issn = {1743-9159}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/methods/*statistics & numerical data ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Carcinoma, Lobular/pathology ; Diagnostic Errors ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {INTRODUCTION: Due to the possibility of underestimation, surgical excision is usually offered to patients with atypical ductal hyperplasia (ADH) diagnosed with core needle biopsy (CNB). Here we review the 10-year data of patients with ADH diagnosed by CNB, aiming to identify the factors associated with under-diagnosis.

METHODS: Retrospective review of database from 1st Jan 2005 to 31st Dec 2014 was performed; patients with ADH diagnosed by CNB were identified. Diagnosis upgrade rate and its risk factors were evaluated.

RESULTS: 104 patients were found to have ADH on CNB, 101 patients received excisional biopsy while 3 patients refused operation. 34 patients had ductal carcinoma in situ (DCIS) after excision, 6 had invasive ductal carcinoma, 1 had lobular carcinoma in situ and 1 had angiosarcoma. CNB under-diagnosed up to 41.6% of malignant lesions. Breast mass on presentation and suspicious mammograms (BIRADS ≥ 4) are associated with diagnosis upgrade (P = 0.0005, 0.0001). Literature review of 39 studies between 1997 and 2017 revealed 3125 excision procedures performed for ADH diagnosed by CNB, the pooled median diagnosis upgrade rate was 25% (Range 4-54%).

CONCLUSION: We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.}, } @article {pmid29145250, year = {2017}, author = {Jung, JH and Son, SH and Kim, DH and Lee, J and Jeong, SY and Lee, SW and Park, HY and Lee, J and Ahn, BC}, title = {CONSORT-Independent prognostic value of asphericity of pretherapeutic F-18 FDG uptake by primary tumors in patients with breast cancer.}, journal = {Medicine}, volume = {96}, number = {46}, pages = {e8438}, pmid = {29145250}, issn = {1536-5964}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis ; Disease-Free Survival ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the prognostic implication of asphericity (ASP); spatial irregularity; of pretherapeutic F 2-deoxy-2-fluoro-D-glucose (F FDG) tumor uptake in patients with invasive ductal carcinoma (IDC) of the breast.

METHODS: One hundred thirty-one female IDC patients (mean age = 48.1 ± 10.4 years), with pathological tumor size greater than 2 cm were retrospectively evaluated using F FDG positron emission tomography/computed tomography (PET/CT). ASP of F FDG distribution was calculated on the basis of the deviation of the tumor shape from spherical symmetry. Progression-free survival (PFS) was predicted on the basis of the univariate and multivariate analyses of the measured clinicopathologic factors and metabolic PET parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)].

RESULTS: The PFS rate among the 131 patients was 90.1%. The mean follow-up time was 50 months for the entire study cohort and 26 months for the patients with recurrent disease. It is evident from the univariate analysis that N stage, hormonal receptor (Estrogen, ER/Progesterone, PR) status, MTV (≤4.2 mL), and ASP (≤15.1%) affected the PFS. Hazard ratios (HRs) estimated from the multivariate Cox regression analysis show that N stage (HR = 17.6), ASP (HR = 11.9), and hormonal receptor status (HR = 6.9) were independent prognostic factors in predicting PFS. In the subgroup of patients with lymph node metastasis, ASP (HR = 10.9) and hormonal receptor status (HR = 9.1) were independent prognostic factors for PFS.

CONCLUSION: ASP of F FDG uptake is an independent predictor of outcome in IDC patients, and can be used for prognostic stratification.}, } @article {pmid29142588, year = {2017}, author = {Mwakigonja, AR and Lushina, NE and Mwanga, A}, title = {Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania.}, journal = {Infectious agents and cancer}, volume = {12}, number = {}, pages = {60}, pmid = {29142588}, issn = {1750-9378}, abstract = {BACKGROUND: Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).

METHODS: A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January-December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).

RESULTS: A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18-75 years and mean age was 48.36 years. Majority (64.3%) were in the 36-55 years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n = 53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n = 46/70) cases were immunostained for HER-2 and 15.2% (n = 7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.

CONCLUSIONS: Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.}, } @article {pmid29142206, year = {2017}, author = {Wang, CQ and Li, Y and Huang, BF and Zhao, YM and Yuan, H and Guo, D and Su, CM and Hu, GN and Wang, Q and Long, T and Wang, Y and Tang, CH and Li, X}, title = {EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15654}, pmid = {29142206}, issn = {2045-2322}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; ErbB Receptors/genetics ; Female ; Gefitinib/administration & dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Microfilament Proteins/*genetics ; Middle Aged ; *Molecular Targeted Therapy ; Neoplasm Recurrence, Local/drug therapy/genetics/pathology ; Progression-Free Survival ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; }, abstract = {Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.}, } @article {pmid29137351, year = {2017}, author = {Sánchez-Cid, L and Pons, M and Lozano, JJ and Rubio, N and Guerra-Rebollo, M and Soriano, A and Paris-Coderch, L and Segura, MF and Fueyo, R and Arguimbau, J and Zodda, E and Bermudo, R and Alonso, I and Caparrós, X and Cascante, M and Rafii, A and Kang, Y and Martínez-Balbás, M and Weiss, SJ and Blanco, J and Muñoz, M and Fernández, PL and Thomson, TM}, title = {MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells.}, journal = {Oncotarget}, volume = {8}, number = {48}, pages = {83384-83406}, pmid = {29137351}, issn = {1949-2553}, abstract = {MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.}, } @article {pmid29137072, year = {2017}, author = {An, YS and Kang, DK and Jung, Y and Kim, TH}, title = {Volume-based metabolic parameter of breast cancer on preoperative 18F-FDG PET/CT could predict axillary lymph node metastasis.}, journal = {Medicine}, volume = {96}, number = {45}, pages = {e8557}, pmid = {29137072}, issn = {1536-5964}, mesh = {Adult ; Axilla ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Lymphatic Metastasis/*diagnostic imaging ; Middle Aged ; Positron Emission Tomography Computed Tomography/*methods ; Predictive Value of Tests ; *Radiopharmaceuticals ; Retrospective Studies ; Tumor Burden ; }, abstract = {The purpose of our study was to evaluate the association between metabolic parameters on FDG PET/CT and axillary lymph node metastasis (ALNM) in patients with invasive breast cancer.From January 2012 to December 2012, we analyzed 173 patients with invasive ductal carcinoma (IDC) who underwent both initial breast magnetic resonance imaging (MRI) and F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) examinations. All metabolic parameters were measured from the tumor volume segmented by a gradient-based method. Once the primary target lesion was segmented, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated automatically by the MIMvista software.Mean age of 173 patients was 49 years. Of 173 patients, 45 (26%) showed ALNM. On univariate analysis, larger tumor size (>2.2 cm; P = .002), presence of lymphovascular invasion (P < .001), higher SUVmax (>2.82; P = .038), higher SUVmean (>1.2; P = .027), higher MTV (>2.38; P < .001), and higher TLG (>3.98; P = .007) were associated with a higher probability of ALNM. On multivariate analysis, presence of lymphovascular invasion (adjusted odds ratio [OR], 11.053; 95% CI, 4.403-27.751; P < .001) and higher MTV (>2.38) (adjusted OR, 2.696; 95% CI, 1.079-6.739; P = .034) maintained independent significance in predicting ALNM. In subgroup analysis of T2/T3 breast cancer, lymphovascular invasion (adjusted OR, 20.976; 95% CI, 5.431-81.010; P < .001) and higher MTV (>2.38) (adjusted OR, 4.906; 95% CI, 1.616-14.896; P = .005) were independent predictors of ALNM. However in T1 breast cancer, lymphovascular invasion (adjusted OR, 16.096; 95% CI, 2.517-102.939; P = .003) and larger SUV mean (>1.2) (adjusted OR, 13.275; 95% CI, 1.233-142.908; P = .033) were independent predictors while MTV was not.MTV may be associated with ALNM in patients with invasive breast cancer, particularly T2 and T3 stages. In T1 breast cancer, SUVmean was associated with ALNM.}, } @article {pmid29137038, year = {2017}, author = {Chen, Y and Liu, Y and Wang, Y and Li, W and Wang, X and Liu, X and Chen, Y and Ouyang, C and Wang, J}, title = {Quantification of STAT3 and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer.}, journal = {Medicine}, volume = {96}, number = {45}, pages = {e8488}, pmid = {29137038}, issn = {1536-5964}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger ; STAT3 Transcription Factor/*biosynthesis ; Vascular Endothelial Growth Factor Receptor-3/*biosynthesis ; Vascular Endothelial Growth Factors/*biosynthesis ; }, abstract = {BACKGROUND: Axillary lymph node metastasis is associated with increased risk of regional recurrence, distant metastasis, and poor survival in breast malignant neoplasm. Expression of signal transducer and activator of transcription 3 (STAT3) is significantly associated with tumor formation, migration, and invasion in various cancers. In addition, vascular endothelial growth factor (VEGF) expression could promote angiogenesis and increase the risk of tumorigenesis. To determine correlations among STAT3 expression, VEGF, and clinicopathological data on lymph node involvement in breast cancer patients after surgery.

METHODS: The mRNA expression levels of STAT3 and VEGFs were measured in 45 breast invasive ductal carcinoma tissues, 45 peritumoral tissues, and 45 adjacent nontumor tissues by real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Postoperative pathological examination revealed explicit axillary lymph node involvement in all patients.

RESULTS: Average mRNA levels of STAT3 and VEGFs were the highest in breast invasive ductal carcinoma tissues, followed by peritumoral tissues. High expression of STAT3 showed significant positive correlation with high axillary lymph node involvement and progesterone receptor (PR), VEGF-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)-3 expression. The expression levels of STAT3, VEGF-C, and VEGFR-3 were significantly higher in the tumor tissues of patients with axillary lymph node metastasis than in those of patients without the metastasis. Expression levels of VEGF-C and VEGFR-3 were also significantly higher in peritumoral tissues of patients with axillary lymph node metastasis. Positive correlations were found between STAT3 and VEGF-C/-D mRNA levels.

CONCLUSION: These data suggest that STAT3/VEGF-C/VEGFR-3 signaling pathway plays an important role in carcinogenesis and lymph-angiogenesis. Our findings suggest that STAT3 may be a potential molecular biomarker for predicting the involvement of axillary lymph nodes in breast cancer, and therapies targeting STAT3 may be important for preventing breast cancer metastasis.}, } @article {pmid29131529, year = {2017}, author = {Yang, LP and Sun, HF and Zhao, Y and Chen, MT and Zhang, N and Jin, W}, title = {Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.}, journal = {Cancer medicine}, volume = {6}, number = {12}, pages = {2867-2875}, pmid = {29131529}, issn = {2045-7634}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Lobular/mortality/*secondary/therapy ; Chi-Square Distribution ; Disease Progression ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; Young Adult ; }, abstract = {The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.}, } @article {pmid29126758, year = {2017}, author = {Helal, DS and El-Guindy, DM}, title = {Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {29}, number = {4}, pages = {177-183}, doi = {10.1016/j.jnci.2017.09.002}, pmid = {29126758}, issn = {2589-0409}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*genetics/*metabolism ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Prognosis ; Protein Transport ; Serpins/*genetics/*metabolism ; Tumor Burden ; }, abstract = {Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.}, } @article {pmid29119195, year = {2017}, author = {Tan, EJ and Moey, T and Madhukumar, P and Leong, LC}, title = {Clinics in diagnostic imaging (180). Ductal carcinoma in situ (DCIS).}, journal = {Singapore medical journal}, volume = {58}, number = {10}, pages = {585-592}, pmid = {29119195}, issn = {2737-5935}, mesh = {Adult ; Biopsy ; Breast/surgery ; Breast Neoplasms/*diagnostic imaging/*therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*therapy ; Cluster Analysis ; *Diagnostic Imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Preoperative Period ; Ultrasonography ; }, abstract = {A 26-year-old woman presented with a slow-growing right breast lump. Excision biopsy of the lump showed invasive ductal carcinoma with adjacent ductal carcinoma in situ (DCIS). Preoperative imaging was performed to assess the extent of disease. Magnetic resonance (MR) imaging of the breasts showed an area of clustered ring enhancement deep to the biopsy site, which was representative of residual DCIS. DCIS is a common noninvasive malignancy that manifests as a primary breast tumour or in association with other lesions. The radiological features of DCIS are discussed herein, with special attention to the clustered ring enhancement pattern on MR imaging.}, } @article {pmid29113229, year = {2017}, author = {Chen, T and Zhou, L and Li, H and Tian, Y and Li, J and Dong, L and Zhao, Y and Wei, D}, title = {Fatty acid synthase affects expression of ErbB receptors in epithelial to mesenchymal transition of breast cancer cells and invasive ductal carcinoma.}, journal = {Oncology letters}, volume = {14}, number = {5}, pages = {5934-5946}, pmid = {29113229}, issn = {1792-1074}, abstract = {The aim of the present study was to investigate changes in the expression of ErbBs during epithelial-mesenchymal transition (EMT) of breast cancer cells and its association with the expression of fatty acid synthase (FASN). MCF-7-MEK5 cells were used as the experimental model, while MCF-7 cells were used as a control. Tumor cells were implanted into nude mice for in vivo analysis. Cerulenin was used as a FASN inhibitor. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect expression levels of FASN and ErbB1-4. Immunohistochemistry was used to detect the expression of FASN and ErbB1-4 in 58 invasive ductal carcinomas (IDC), as well as their association with clinicopathological characteristics. The expression of FASN and ErbB1-4 in MCF-7-MEK5 cells and tumor tissues increased significantly compared with controls (P<0.001). Inhibition of FASN by cerulenin resulted in a significant decrease in expression of ErbB1, 2 and 4 (P<0.001), whereas there was no evident change in ErbB3. In IDC samples, the expression of FASN and ErbB1-4 increased considerably in lymph node metastases compared with non-lymph node metastases (P<0.05). ErbB2 expression increased in advanced clinical stages (II, III and IV) of IDC and in tumors with larger diameters (P<0.05). The expression of ErbB3 increased in ER-positive tumors (P<0.05). Additionally, a positive association between the expression of FASN and ErbB1, 2 and 4 was observed (P<0.05). FASN activates ErbB1, 2 and 4, and their dimers, which are polymerized via the microstructural domain of the cell membrane. This may initiate EMT and consequentlyincrease the invasion and migration of cancer cells. However, ErbB3 may also affect tumor progression via a FASN-independent pathway.}, } @article {pmid29113216, year = {2017}, author = {Liu, X and Guan, Y and Wang, L and Niu, Y}, title = {MicroRNA-10b expression in node-negative breast cancer-correlation with metastasis and angiogenesis.}, journal = {Oncology letters}, volume = {14}, number = {5}, pages = {5845-5852}, pmid = {29113216}, issn = {1792-1074}, abstract = {Metastasis accounts for the majority of cases of mortality in patients with axillary lymph node-negative (ANN) breast cancer. Angiogenesis is an essential component of the metastatic pathway. Studies regarding microRNA (miR)-10b expression in patients with ANN breast cancer and the function of angiogenesis in breast cancer remain scarce. The present study was performed in order to determine the biological significance of miR-10b, and investigate the association between miR-10b and microvessel density (MVD) measured in ANN breast cancer. miR-10b expression and immunohistochemical analysis for MVD were assessed in 195 patients with ANN of invasive ductal carcinoma, including 65 cases with distant metastasis 'poor group', and 130 cases without any recurrence 'good group'. miR-10b expression was higher in the 'poor group' (73.8%) compared with that in the 'good group' (51.5%; P=0.003). Multivariate logistic regression demonstrated that miR-10b retained independent prognostic significance for distant metastasis along with MVD and vascular invasion. Among 195 patients, miR-10b expression was significantly associated with tumor grade, tumor size and molecular subtypes (P<0.05). In addition, miR-10b expression was positively associated with the MVD count (r=0.370; P<0.001), tumor grade (r=0.168; P=0.019) and tumor size (r=0.175; P=0.014). The results of the current study suggest that miR-10b is a useful marker for predicting metastasis and angiogenesis in ANN breast cancer.}, } @article {pmid29103479, year = {2017}, author = {Benveniste, AP and Ortiz-Perez, T and Ebuoma, LO and Sepulveda, KA and Severs, FJ and Roark, A and Wang, T and Sedgwick, EL}, title = {Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with pure ductal carcinoma in situ (DCIS)?.}, journal = {European journal of radiology}, volume = {96}, number = {}, pages = {74-79}, doi = {10.1016/j.ejrad.2017.09.014}, pmid = {29103479}, issn = {1872-7727}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; *Mammography ; Middle Aged ; Neoplasm Invasiveness/*diagnostic imaging/pathology ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: To determine if breast MRI is useful for detecting additional or invasive sites of disease in patients initially diagnosed with pure DCIS.

MATERIALS AND METHODS: A retrospective review of women diagnosed with pure DCIS who underwent a breast MRI for evaluation of extent of disease was performed at a single institution from January 2013 to April 2015. Data analysis included imaging (mammography, ultrasound and MRI) and pathology characteristics (histology and biomarker status) of the primary DCIS as well as descriptors for the additional sites of disease incidentally found by breast MRI.

RESULTS: A total of 108 patients were diagnosed with pure DCIS during this time period. A breast MRI for staging was recommended for all patients. 76 patients had an MRI performed, ages ranging from 38 to 79 years old (median, 53 years); sizes ranging from 0.3 to 10cm (mean, 2.2cm). A total of 52 patients (68%) either had suspicious new finding(s) (n=27, 36%) or bigger tumor size than originally visualized on mammography (n=43, 57%). A total of twenty-seven patients (36%) had other MRI findings suspicious for additional sites of disease in either breast (four in the ipsilateral breast and twenty-three in the contralateral breast). From this group of patients, twenty-three (85%) patients underwent MRI-guided biopsy as recommended. The four patients who did not have the recommended MRI guided-biopsy either underwent total mastectomies or refused the biopsy. Six out of the twenty-three patients (26%) were diagnosed with an additional site of cancer (5 DCIS and 1 IDC) (7.9%, CI=3.7%, 16.2%). All of the six patients had contralateral disease (100%) and none had a second site of disease in the ipsilateral breast. The size of the additional sites of disease ranged from 0.4 to 8cm (mean, 3.1cm) and the size of the primary lesion in this selected group ranged from 0.1 to 10.9cm (mean, 5.6cm). Ages ranged from 44 to 63 years old (median, 52.5 years). Five out 6 patients (83%) presented with the first site of disease as pure DCIS with estrogen (ER) and progesterone (PR) receptors positive and one case (17%) was pure DCIS ER/PR- negative. The second incidental lesion found on MRI demonstrated 5 cases of contralateral pure DCIS and 1 case of contralateral invasive disease. From this group, we did not have the data for biomarker analysis for the second site of disease in 2 cases and 3 cases showed concordant biomarker status between the first and second sites of disease. The 1 case that presented with an invasive component in the contralateral side of the initially biopsy-proven pure DCIS had discordant biomarkers compared to the first site of disease: the first site of pure DCIS was ER/PR-negative and the second site of invasive ductal carcinoma (IDC) presented with ER/PR-positive status.

CONCLUSION: From a total of 76 patients with recent diagnosis of pure DCIS who underwent staging breast MRI examination for diagnosis of additional sites of disease, approximately 8% (95% confidence interval=3.7%, 16.2%) was diagnosed with an additional site of cancer and 1.3% (95% confidence interval=0.2%, 7%) of the total cases had invasive disease in the additional sites with different biomarker status; changing their management and prognosis.}, } @article {pmid29095373, year = {2017}, author = {Pihet, S and Moses Passini, C and Eicher, M}, title = {Good and Bad Days: Fluctuations in the Burden of Informal Dementia Caregivers, an Experience Sampling Study.}, journal = {Nursing research}, volume = {66}, number = {6}, pages = {421-431}, doi = {10.1097/NNR.0000000000000243}, pmid = {29095373}, issn = {1538-9847}, mesh = {Activities of Daily Living ; Adaptation, Psychological ; Aged ; Caregivers/*psychology ; *Cost of Illness ; Dementia/*psychology/therapy ; Female ; Humans ; Male ; Middle Aged ; Quality of Life/*psychology ; Sampling Studies ; Social Support ; Stress, Psychological/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Informal dementia caregivers (IDCs) are often confronted with important fluctuations in care-related burden, commonly described as "good and bad days." These fluctuations are overlooked by traditional questionnaires focusing on the average experience. The experience sampling method (ESM) is based on the repeated collection of data in everyday life, thereby allowing the description of day-to-day fluctuations in IDC burden, and the identification of their correlates. ESM studies are still scarce among IDCs, with none focusing on day-to-day fluctuations in burden.

OBJECTIVES: This ESM study aimed to examine day-to-day fluctuations in the burden of IDCs and test their associations with six moment-to-moment predictors.

METHODS: Primary IDCs (N = 26, median age = 68 years, 77% women, 73% spouses) volunteered to answer questions about their daily burdens, patients' memories and behavioral problems (MBP), caregivers' MBP-related distress, psychological distress, self-efficacy and positive affects, and relationship quality; volunteers did this every evening for 2 weeks on a touchpad, resulting in 206 measures. Data were analyzed with multilevel linear regression.

RESULTS: Day-to-day fluctuations covered about two thirds of the total variance for most study variables. All six predictors had a significant bivariate relation with daily burden, explaining 15%-32% of its fluctuations, with significant differences between caregivers in the strength of these relations. The best multivariate model explained 51% of the day-to-day fluctuations in burden. It included caregiver MBP-related distress, psychological distress, and relationship quality.

DISCUSSION: This innovative study of IDC burden shows that day-to-day fluctuations are an important part of caregivers' real-life experiences and that half of this variability is predicted by currently understudied factors. Inviting caregivers to monitor clinical outcomes daily over 1 or 2 weeks could help tailor interventions to their individual needs and also empower them.}, } @article {pmid29094384, year = {2018}, author = {Kato, M and Kimura, K and Hirakawa, A and Kobayashi, Y and Ishida, R and Kamihira, O and Majima, T and Funahashi, Y and Sassa, N and Matsukawa, Y and Hattori, R and Gotoh, M and Tsuzuki, T}, title = {Prognostic parameter for high risk prostate cancer patients at initial presentation.}, journal = {The Prostate}, volume = {78}, number = {1}, pages = {11-16}, doi = {10.1002/pros.23438}, pmid = {29094384}, issn = {1097-0045}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/*pathology ; Prostatic Neoplasms/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer.

METHODS: We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed.

RESULTS: The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS).

CONCLUSIONS: The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.}, } @article {pmid29093554, year = {2017}, author = {Lu, TY and Kadir, K and Ngeow, WC and Othman, SA}, title = {The Prevalence of Double Eyelid and the 3D Measurement of Orbital Soft Tissue in Malays and Chinese.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {14819}, pmid = {29093554}, issn = {2045-2322}, mesh = {Adult ; Anthropometry/methods ; Asian People ; Eyelids/*anatomy & histology ; Female ; Humans ; Imaging, Three-Dimensional/methods ; Male ; Photogrammetry/methods ; Prevalence ; Young Adult ; }, abstract = {This study aimed to determine the prevalence of double eyelid among two main Mongoloid ethnicities, the Malays and Chinese who reside in Malaysia. We also measured their periorbital tissue parameters for application in anthropology, optometry, ophthalmology, oculoplastic surgery and maxillofacial trauma surgery. The images of the 103 Malay and 97 Chinese volunteers were captured using indirect 3D photogrammetry, and quantitative measurement was obtained using the software provided by the manufacturer. All Malays and 70.1% of Chinese in this cross section population had double eyelid on both eyes. The mean pretarsal skin height was 3.99 mm for the Malays and 2.29 mm for the Chinese. The Malays appeared to have shorter eyebrow height (11.10 mm) compared to the Chinese (11.79 mm). An opposite pattern could be seen in the measurement of upper eyelid crease height between the Malays (8.33 mm) and the Chinese (4.91 mm). Of note, the intercanthal distance of the Chinese (IDC = 35.85 mm) was wider and their interpupillary distance was narrower (IPD = 62.85 mm) compared to the Malays' (ICD = 34.21 mm; IPD = 64.04 mm). In conclusion, there were significant differences in the prevalence of double eyelid and periorbital tissue measurements between the Malays and Chinese.}, } @article {pmid29090670, year = {2018}, author = {Gurzu, S and Banias, L and Bara, T and Feher, I and Bara, T and Jung, I}, title = {The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.}, journal = {Recent patents on anti-cancer drug discovery}, volume = {13}, number = {1}, pages = {118-124}, doi = {10.2174/2212798409666171101121108}, pmid = {29090670}, issn = {2212-3970}, mesh = {Aged ; Breast Neoplasms/diagnosis/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Female ; Humans ; Neoplasms, Second Primary/diagnosis/*metabolism/secondary ; Stomach Neoplasms/diagnosis/*metabolism/secondary ; }, abstract = {BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood.

OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells.

METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents.

RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, β-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma.

CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/β-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.}, } @article {pmid29089813, year = {2017}, author = {Hendren, E and Vinik, O and Faragalla, H and Haq, R}, title = {Breast cancer and dermatomyositis: a case study and literature review.}, journal = {Current oncology (Toronto, Ont.)}, volume = {24}, number = {5}, pages = {e429-e433}, pmid = {29089813}, issn = {1198-0052}, abstract = {A 49-year-old woman presents with an extensive violaceous rash, rapidly progressive proximal muscle weakness, and dysphagia to solids, consistent with a diagnosis of dermatomyositis. Two weeks later, she palpates a mass in her left breast and is diagnosed with her2-positive metastatic invasive ductal carcinoma of the breast. There is a well-established association between dermatomyositis and malignancy. However, the specific association between breast cancer and dermatomyositis has not been well characterized. No guideline for oncologists managing these patients has been established. Recently, 3 cases of breast cancer and dermatomyositis were diagnosed at our institution. A review of the literature was pursued to characterize the association between breast cancer and dermatomyositis. A review of 178 papers identified 22 cases of breast cancer with dermatomyositis. Most patients (71%) presented with stage iii or iv breast cancer. The median time between the diagnosis of breast cancer and the onset of dermatomyositis symptoms was 1 month. Three quarters of the patients were steroid-responsive and able to taper. Half the women with follow-up data experienced a documented cancer relapse associated with a new flare of cutaneous symptoms. The presence of dermatomyositis appears to be associated with more-advanced breast cancer stage and is most commonly associated with invasive ductal carcinoma. In our review, treatment of cancer alone is insufficient to adequately control the cutaneous and myopathic manifestations of dermatomyositis, which can significantly affect quality of life. A multidisciplinary approach, including close collaboration with rheumatologists and dermatologists, is therefore important in the diagnosis and management of oncology patients with dermatomyositis.}, } @article {pmid29089571, year = {2017}, author = {Gao, Z and Li, G and Li, X and Zhou, J and Duan, X and Chen, J and Joshi, BP and Kuick, R and Khoury, B and Thomas, DG and Fields, T and Sabel, MS and Appelman, HD and Zhou, Q and Li, H and Kozloff, K and Wang, TD}, title = {In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {14404}, pmid = {29089571}, issn = {2045-2322}, support = {P30 CA046592/CA/NCI NIH HHS/United States ; R01 CA142750/CA/NCI NIH HHS/United States ; U01 CA189291/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/*metabolism/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology ; Cell Line, Tumor ; Female ; Fluorescent Dyes/chemistry ; Mice, Nude ; Microscopy, Confocal/*methods ; Neoplasm Transplantation ; Optical Imaging/*methods ; Peptides/chemistry ; Photoacoustic Techniques/methods ; Receptor, ErbB-2/chemistry/*metabolism ; Tomography/*methods ; }, abstract = {ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo. We used IRDye800CW as the fluorophore, validated performance characteristics for specific peptide binding to cells in vitro, and investigated peak peptide uptake in tumors using photoacoustic tomography. We performed real-time optical imaging using a handheld dual-axes confocal fluorescence endomicroscope that collects light off-axis to reduce tissue scattering for greater imaging depths. Optical sections in either the vertical or horizontal plane were collected with sub-cellular resolution. Also, we found significantly greater peptide binding to pre-clinical xenograft breast cancer in vivo and to human specimens of invasive ductal carcinoma that express ErbB2 ex vivo. We used a scrambled peptide for control. Peptide biodistribution showed high tumor uptake by comparison with other organs to support safety. This novel integrated imaging strategy is promising for visualizing ErbB2 expression in breast tumors and serve as an adjunct during surgery to improve diagnostic accuracy, identify tumor margins, and stage early cancers.}, } @article {pmid29085497, year = {2017}, author = {Wang, Q and Sun, L and Yan, J and Wang, S and Zhang, J and Zheng, X}, title = {Expression of vascular endothelial growth factor and caspase-3 in mucinous breast carcinoma and infiltrating ductal carcinoma-not otherwise specified, and the correlation with disease-free survival.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4890-4896}, pmid = {29085497}, issn = {1792-1074}, abstract = {Mucinous breast carcinoma (MBC) is a rare type of breast cancer, but it has been infrequently studied due to its associated good prognosis. Vascular endothelial growth factor (VEGF) and caspase-3 have been identified to be prognostic factors of infiltrating ductal carcinoma-not otherwise specified (IDC-NOS), but their expression in MBC has not been reported. In the present study, the expression of caspase-3 and VEGF in MBC and IDC-NOS were assessed by immunohistochemistry. Scoring was conducted based on staining intensity and percentage of positive cells. Based on the scores of caspase-3 and VEGF expression, all patient samples were divided into two groups: Low expression (score of 0-5) or high expression (score of 6-12). In total, 42.59% of MBC patients exhibited a high VEGF score compared with 61.67% of the IDC-NOS group (P<0.05). Furthermore, 57.41% of MBC patients exhibited high caspase-3 expression compared with only 33.33% of IDC-NOS patients (P<0.05). VEGF expression in MBC was associated with age, nodal status and tumor-node-metastasis (TNM) stage. Cox univariate analysis showed that higher VEGF expression, positive nodal status and higher TNM stage were associated with shorter disease-free survival (DFS). The Kaplan-Meier method showed that higher VEGF expression in MBC was associated with worse DFS times, while Cox multivariate analysis showed that only TNM stage was significantly associated with DFS. VEGF and caspase-3 expression varied in the MBC and IDC-NOS samples, but neither was directly correlated with DFS in the MBC patients.}, } @article {pmid29085490, year = {2017}, author = {Cho, SG}, title = {APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4845-4852}, pmid = {29085490}, issn = {1792-1074}, abstract = {Canonical WNT signaling promotes breast cancer progression. Although APC downregulated 1 (APCDD1) may inhibit canonical WNT signaling, its role in breast cancer remains to be fully understood. The present study demonstrated that APCDD1 suppressed in vitro breast cancer growth and metastasis by inhibiting canonical WNT signaling. The present study demonstrated that APCDD1 expression was negatively associated with breast cancer cell invasion, which was consistent with previous studies that indicated that APCDD1 expression was decreased in invasive ductal carcinoma compared with that in ductal carcinoma in situ. Furthermore, APCDD1 expression was negatively associated with nuclear β-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study. Silencing APCDD1 in non-invasive breast cancer cells using lentiviral APCDD1 short hairpin RNAs enhanced migration and invasion, which may be mediated by canonical WNT signaling, whereas the overexpression of human influenza hemagglutinin-tagged APCDD1 in invasive breast cancer cells repressed these properties. Therefore, the present study suggested that APCDD1 regulated breast cancer progression by targeting canonical WNT signaling and modulating breast cancer cell invasion.}, } @article {pmid29085457, year = {2017}, author = {Razia, S and Nakayama, K and Tsukao, M and Nakamura, K and Ishikawa, M and Ishibashi, T and Ishikawa, N and Sanuki, K and Yamashita, H and Ono, R and Hossain, MM and Minamoto, T and Kyo, S}, title = {Metastasis of breast cancer to an endometrial polyp, the cervix and a leiomyoma: A case report and review of the literature.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4585-4592}, pmid = {29085457}, issn = {1792-1074}, abstract = {Haematogenous metastases of breast cancer tumors has previously been demonstrated to frequently occur at the sites of the lung, bones, liver and brain, however presence in the uterine remains a rare occurrence. Metastatic carcinoma of the uterus usually originates from other genital sites, most frequently from the ovaries. The current review presents the first reported case of lobular breast carcinoma metastasizing to an endometrial polyp, the cervix and a leiomyoma simultaneously. The patient (58 years, female) first presented with abnormal uterine bleeding. Invasive ductal carcinoma had previously been diagnosed in her right breast, with lobular and ductal cancer cells observed to be present in her lymph nodes. A hysteroscopic procedure to examine the postmenopausal bleeding revealed an endometrial polyp, which was subsequently resected. The morphology and immunohistochemical studies confirmed the diagnosis of metastasis of lobular breast carcinoma to an endometrial polyp. An [18]F fludeoxyglucose positron emission tomography/computed tomography (PET-CT) scan performed following the diagnosis, revealed a slightly increased uptake in the myoma, which is often observed in benign uterine leiomyoma. The patient then underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy and partial colectomy. Pathology results demonstrated that the uterine leiomyoma and cervix shared the same histopathological features as those presented by the primary lobular breast carcinoma. Although rare, breast tumors may metastasize to an endometrial polyp, cervix and leiomyoma concurrently in patients, therefore physicians may now consider the potential of the diagnosis of metastatic spread to the genital tract, in a patient with abnormal uterine bleeding and a history of lobular breast cancer. Gynecologists planning a laparoscopic hysterectomy for a patient with a history of lobular breast carcinoma may consider abdominal rather than laparoscopic hysterectomy, as lobular carcinoma is difficult to detect. The use of PET-CT may be beneficial for the identification of an unexpected mass.}, } @article {pmid29084692, year = {2017}, author = {Chen, K and Wang, CQ and Fan, YQ and Xie, YS and Yin, ZF and Xu, ZJ and Zhang, HL and Cao, JT and Wang, Y and Gao, L}, title = {Model design for screening effective Antihyperlipidemic drugs using zebrafish system.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {30}, number = {5}, pages = {1697-1707}, pmid = {29084692}, issn = {1011-601X}, mesh = {Animals ; Atorvastatin/pharmacology ; Biomarkers/blood ; Cholesterol/blood ; Diet, High-Fat ; Disease Models, Animal ; Drug Discovery/*methods ; Ezetimibe/pharmacology ; Fenofibrate/pharmacology ; *High-Throughput Screening Assays ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hyperlipidemias/blood/*drug therapy/etiology ; Hypolipidemic Agents/*pharmacology ; Lipid Metabolism/*drug effects ; Male ; Triglycerides/blood ; Zebrafish/*blood ; }, abstract = {The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 μM/37.0μM, 1.2μM/3.5μM, and 6.3 μM/26.4μM, respectively, while, the intermediate (IDC) was, in order, 18.5μM, 1.8μM, 13.2μM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.}, } @article {pmid29082377, year = {2017}, author = {Madubogwu, CI and Ukah, CO and Anyanwu, S and Chianakwana, GU and Onyiaorah, IV and Anyiam, D}, title = {Sub-classification of Breast Masses by Fine Needle Aspiration Cytology.}, journal = {European journal of breast health}, volume = {13}, number = {4}, pages = {194-199}, pmid = {29082377}, issn = {2587-0831}, abstract = {OBJECTIVE: The aim of this study is to evaluate the accuracy of sub-classification of breast diseases using Fine Needle Aspiration cytology (FNAC).

MATERIALS AND METHODS: A one-year prospective study of 180 consecutive patients with palpable breast lesions who underwent FNAC and subsequently open surgical biopsy for histological confirmation. FNAC was used to sub-classify breast lesions and then correlated with histological diagnosis.

RESULTS: A total of 180 patients were enrolled into the study but only 110 patients with histology report were used for test validity. Seventeen (15.5%) smears were C1; while 46 (41.8%), 5 (4.5%), 4 (3.6%) and 38 (34.6%) were C2, C3, C4 and C5, respectively. FNAC achieved sensitivity of 90.0%, specificity of 95.5%, false positive rate of 5.3%, false negative rate of 8.7%, positive predictive value of 94.7%, negative predictive value of 91.3% and overall diagnostic accuracy of 92.9%. Only 86 (78.2%) of the 110 smears could be sub-classified into different disease conditions of the breast on cytology. FNAC accurately sub-classified 25(78.1%) of fibroadenoma and 28(87.5%) of invasive ductal carcinoma.

CONCLUSION: FNAC can reasonably sub-classify fibroadenoma, invasive ductal carcinoma and mastitis but there is still a challenge with lobular carcinomas, metaplastic carcinomas, papillary carcinomas and fibrocystic changes.}, } @article {pmid29076877, year = {2018}, author = {Skálová, A and Stenman, G and Simpson, RHW and Hellquist, H and Slouka, D and Svoboda, T and Bishop, JA and Hunt, JL and Nibu, KI and Rinaldo, A and Vander Poorten, V and Devaney, KO and Steiner, P and Ferlito, A}, title = {The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.}, journal = {The American journal of surgical pathology}, volume = {42}, number = {2}, pages = {e11-e27}, doi = {10.1097/PAS.0000000000000980}, pmid = {29076877}, issn = {1532-0979}, mesh = {Biomarkers, Tumor/*genetics ; Biopsy ; Carcinoma/*genetics/pathology/therapy ; Diagnosis, Differential ; Gene Fusion ; Genetic Predisposition to Disease ; Humans ; *Molecular Diagnostic Techniques ; Mutation ; Neoplasm Grading ; Phenotype ; Predictive Value of Tests ; Salivary Gland Neoplasms/*genetics/pathology/therapy ; Translocation, Genetic ; }, abstract = {Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.}, } @article {pmid29072365, year = {2017}, author = {Chen, H and Wu, K and Wang, M and Wang, F and Zhang, M and Zhang, P}, title = {Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.}, journal = {Cancer medicine}, volume = {6}, number = {12}, pages = {2775-2786}, pmid = {29072365}, issn = {2045-7634}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*mortality/secondary/therapy ; Carcinoma, Papillary/chemistry/*mortality/secondary/therapy ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; }, abstract = {There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation.}, } @article {pmid29070862, year = {2017}, author = {Takiyama, A and Teramoto, T and Suzuki, H and Yamashiro, K and Tanaka, S}, title = {Persistent homology index as a robust quantitative measure of immunohistochemical scoring.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {14002}, pmid = {29070862}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Immunohistochemistry/*methods ; Middle Aged ; *Observer Variation ; }, abstract = {Immunohistochemical data (IHC) plays an important role in clinical practice, and is typically gathered in a semi-quantitative fashion that relies on some degree of visual scoring. However, visual scoring by a pathologist is inherently subjective and manifests both intra-observer and inter-observer variability. In this study, we introduce a novel computer-aided quantification methodology for immunohistochemical scoring that uses the algebraic concept of persistent homology. Using 8 bit grayscale image data derived from 90 specimens of invasive ductal carcinoma of the breast, stained for the replicative marker Ki-67, we computed homology classes. These were then compared to nuclear grades and the Ki-67 labeling indices obtained by visual scoring. Three metrics for IHC staining were newly defined: Persistent Homology Index (PHI), center coordinates of positive and negative groups, and the sum of squares within groups (WSS). This study demonstrates that PHI, a novel index for immunohistochemical labeling using persistent homology, can produce highly similar data to that generated by a pathologist using visual evaluation. The potential benefits associated with our novel technology include both improved quantification and reproducibility. Since our method reflects cellularity and nuclear atypia, it carries a greater quantity of biologic data compared to conventional evaluation using Ki-67.}, } @article {pmid29069648, year = {2017}, author = {Huang, R and Han, J and Liang, X and Sun, S and Jiang, Y and Xia, B and Niu, M and Li, D and Zhang, J and Wang, S and Wei, W and Liu, Q and Zheng, W and Zhang, G and Song, Y and Panga, D}, title = {Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {43}, number = {6}, pages = {2212-2225}, doi = {10.1159/000484300}, pmid = {29069648}, issn = {1421-9778}, mesh = {Androgen Receptor Antagonists/*pharmacology/therapeutic use ; Anilides/*pharmacology/therapeutic use ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/mortality/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Nitriles/*pharmacology/therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Androgen/chemistry/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Signal Transduction/drug effects ; Tosyl Compounds/*pharmacology/therapeutic use ; Transcription, Genetic/*drug effects ; Transplantation, Heterologous ; beta Catenin/genetics/*metabolism ; }, abstract = {BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment.

METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer.

RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer.

CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.}, } @article {pmid29065116, year = {2017}, author = {Picillo, M and Pivonello, R and Santangelo, G and Pivonello, C and Savastano, R and Auriemma, R and Amboni, M and Scannapieco, S and Pierro, A and Colao, A and Barone, P and Pellecchia, MT}, title = {Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson's disease.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186508}, pmid = {29065116}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cognition Disorders/*blood/complications ; Female ; Humans ; Insulin-Like Growth Factor I/*metabolism ; Male ; Middle Aged ; Parkinson Disease/blood/*complications ; }, abstract = {OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.

METHODS: Serum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.

RESULTS: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (β = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (β = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (β = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).

CONCLUSIONS: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.}, } @article {pmid29064753, year = {2018}, author = {Giess, CS and Chesebro, AL and Chikarmane, SA}, title = {Ultrasound Features of Mammographic Developing Asymmetries and Correlation With Histopathologic Findings.}, journal = {AJR. American journal of roentgenology}, volume = {210}, number = {1}, pages = {W29-W38}, doi = {10.2214/AJR.17.18223}, pmid = {29064753}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma/*diagnostic imaging/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Reproducibility of Results ; Retrospective Studies ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: The purpose of this study is to review the ultrasound (US) features of developing asymmetries and correlate them with histopathologic findings.

MATERIALS AND METHODS: We searched the mammography database of an academic medical center, affiliated cancer center, and two ambulatory imaging facilities from 2009 to 2012 and identified 201 patients with developing asymmetries, 187 of whom had US at the time of, or within 1 month of, diagnostic mammography evaluation. Seventy-five (40.1%) of these 187 patients had a US correlate, and three additional patients had a positive second-look US after MRI (US results were initially negative), and one patient had a US correlate for a newly palpable developing asymmetry 1 month after receiving a BI-RADS category 3 mammography-only assessment. These 78 developing asymmetries with US correlates comprised the study cases. US features were obtained by consensus image review; patient demographic characteristics and outcomes were obtained from the electronic medical record.

RESULTS: Thirty-six of 78 US correlates (46.2%) were masses, the echotexture of which was as follows: 26 (72.2%) were hypoechoic, four (11.1%) were hyperechoic, three (8.3%) were mixed hyperechoic and hypoechoic, and three (8.3%) were anechoic. Forty-two of 78 US correlates (53.8%) were nonmass findings, the echotexture of which was as follows: 24 (57.1%) were mixed hyperechoic and hypoechoic, 13 (31.0%) were hypoechoic, and five (11.9%) were hyperechoic. Twenty-one of 78 lesions (26.9%) were malignant; of these, eight were invasive ductal carcinoma, seven were invasive lobular carcinoma, three were mixed invasive ductal and lobular carcinoma, and three were ductal carcinoma in situ. Malignant findings on US included 17 masses (81.0%) (13 hypoechoic and four mixed hyperechoic and hypoechoic), and four nonmass findings (19.0%) (three mixed hyperechoic and hypoechoic and one hypoechoic).

CONCLUSION: When present, US correlates for developing asymmetries are often nonmass findings with mixed echotexture. Most malignant developing asymmetries with US correlates present as a hypoechoic mass, but 19% present as a nonmass finding with either mixed hyperechoic and hypoechoic echotexture or hypoechoic echotexture.}, } @article {pmid29061022, year = {2017}, author = {Li, XS and Song, YL and Li, DC and Zhu, HX and Meng, LM and Huang, RR and Wang, SL and Wang, D and Fang, H and Fan, HX}, title = {[Preoperative dynamic contrast-enhanced MRI can reduce the rate of tumor-positive resection margins after breast conserving surgery in patients with early non-mass breast carcinoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {39}, number = {10}, pages = {768-774}, doi = {10.3760/cma.j.issn.0253-3766.2017.10.010}, pmid = {29061022}, issn = {0253-3766}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology/surgery ; Case-Control Studies ; *Contrast Media ; Female ; Humans ; Logistic Models ; Magnetic Resonance Imaging/*methods ; Mammography ; *Margins of Excision ; *Mastectomy, Segmental ; Middle Aged ; Preoperative Period ; }, abstract = {Objective: To investigate the value of preoperative dynamic contrast-enhanced MRI in reducing the rate of tumor-positive resection margins after breast conserving surgery in patients with early non-mass breast carcinoma. Methods: Seventy-two patients with early non-mass breast carcinoma received ultrasonographic and mammographic examination and subsequently underwent dynamic contrast-enhanced MRI examination before breast conserving surgery. The control group consisted of 74 patients who had early non-mass breast carcinoma. They only received ultrasonographic and mammographic examination and didn't undergo contrast-enhanced MRI examination. The comparison of the rate of tumor-positive resection margins between two groups was performed. The MRI findings that had the significant influence on the rate of tumor-positive resection margins were analyzed using Logistic regression model. Results: In 28 patients (28/72, 38.9%), dynamic contrast-enhanced MRI could correct or supplement the ultrasonographic and mammographic findings and resulted in the reasonable change of surgical program. The preoperative MRI examination group (n=30) had lower rate of tumor-positive resection margins than control group for invasive ductal carcinoma (23.3% vs 40.0%, P=0.02), but there was no significant difference (21.4% vs 26.9%, P=0.10) between two groups for ductal carcinoma in situ (n=28). The preoperative MRI examination group (n=14) had lower rate of tumor-positive resection margins than control group for the other pathologic types of breast carcinoma (14.3% vs 38.9%, P=0.02). The statistical analysis on the basis of Logistic regression model showed that some main MRI findings, including change surrounding the tumor, distance between tumor and nipple and tumor size, had the significant influence on the rate of tumor-positive resection margins. Conclusion: Preoperative dynamic contrast-enhanced MRI significantly increased the accuracy of resection margins evaluation, and greatly reduced the rate of tumor-positive resection margins after breast conserving surgery in patients with early non-mass breast carcinoma.}, } @article {pmid29060062, year = {2017}, author = {Fridman, G}, title = {Safe Direct Current Stimulator design for reduced power consumption and increased reliability.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2017}, number = {}, pages = {1082-1085}, pmid = {29060062}, issn = {2694-0604}, support = {F32 DC009917/DC/NIDCD NIH HHS/United States ; R01 DC009255/DC/NIDCD NIH HHS/United States ; R01 NS092726/NS/NINDS NIH HHS/United States ; R21 NS081425/NS/NINDS NIH HHS/United States ; }, mesh = {Cochlear Implants ; *Electric Stimulation Therapy ; Electrodes, Implanted ; Equipment Design ; Nervous System ; Neurons ; Reproducibility of Results ; }, abstract = {Current state of the art neural prosthetics, such as cochlear implants, spinal cord stimulators, and deep brain stimulators use implantable pulse generators (IPGs) to excite neural activity. Inhibition of neural firing is typically indirect and requires excitation of neurons that then have inhibitory projections downstream. Safe Direct Current Stimulator (SDCS) technology is designed to convert electronic pulses delivered to electrodes embedded within an implantable device to ionic direct current (iDC) at the output of the device. iDC from the device can then control neural extracellular potential with the intent of being able to not only excite, but also inhibit and sensitize neurons, thereby greatly expanding the possible applications of neuromodulation therapies and neural interface mechanisms. While the potential applications and proof of concept of this device have been the focus of previous work, the published descriptions of this technology leave significant room for power and reliability optimization. We describe and model a novel device construction designed to reduce power consumption by a factor of 12 and to improve its reliability by a factor of 8.}, } @article {pmid29056512, year = {2017}, author = {Rios Garcia, M and Steinbauer, B and Srivastava, K and Singhal, M and Mattijssen, F and Maida, A and Christian, S and Hess-Stumpp, H and Augustin, HG and Müller-Decker, K and Nawroth, PP and Herzig, S and Berriel Diaz, M}, title = {Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence.}, journal = {Cell metabolism}, volume = {26}, number = {6}, pages = {842-855.e5}, doi = {10.1016/j.cmet.2017.09.018}, pmid = {29056512}, issn = {1932-7420}, mesh = {Acetyl-CoA Carboxylase/genetics/*metabolism ; Acetylation ; Animals ; Breast Neoplasms/*metabolism/*pathology ; Disease Models, Animal ; Female ; HEK293 Cells ; Humans ; Leptin/metabolism ; Lung Neoplasms/*secondary ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/metabolism/*pathology ; Tissue Array Analysis ; }, abstract = {Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. ACC1 phosphorylation was mediated by TGFβ-activated kinase (TAK) 1, and ACC1 inhibition was indispensable for the elevation of cellular acetyl-CoA, the subsequent increase in Smad2 transcription factor acetylation and activation, and ultimately epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency worsened tumor recurrence upon primary tumor resection in mice, and ACC1 phosphorylation levels correlated with metastatic potential in breast and lung cancer patients. Given the demonstrated effectiveness of anti-leptin receptor antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines a "metabolocentric" approach in metastatic breast cancer therapy.}, } @article {pmid29052527, year = {2017}, author = {Chen, HR and Wu, YT and Yu, QB and Yang, YY and Wei, YX and Li, HY and Wu, KN and Kong, LQ}, title = {Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.}, journal = {World journal of surgical oncology}, volume = {15}, number = {1}, pages = {189}, pmid = {29052527}, issn = {1477-7819}, mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Biopsy, Large-Core Needle ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary/therapy ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Receptor, ErbB-2/antagonists & inhibitors/*genetics ; Trastuzumab/therapeutic use ; }, abstract = {BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting.

CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3 weeks for 1 year.

CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.}, } @article {pmid29051834, year = {2017}, author = {Jeong, D and Bui, M and Peterson, D and Montilla-Soler, J and Gage, KL}, title = {FDG avid breast cancer bone metastases silent on CT and scintigraphy: a case report with radiologic-pathologic correlation.}, journal = {Acta radiologica open}, volume = {6}, number = {10}, pages = {2058460117734243}, pmid = {29051834}, issn = {2058-4601}, abstract = {Bone is the one of the most common distant metastatic sites in breast cancer. Routine initial breast cancer staging evaluation typically includes computed tomography (CT) and skeletal scintigraphy while 18F fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is reserved for clinically high-risk cases. Since FDG PET-CT is not routinely performed during staging or surveillance evaluations, it is important for radiologists and clinicians to appreciate the limitations of bone metastasis detection on CT and scintigraphy. We present a case of bony metastases of invasive ductal carcinoma of the breast which were not detected on diagnostic CT or skeletal scintigraphy but were metabolically active on FDG PET-CT and evident on magnetic resonance. We provide a review of the literature and radiologic-pathologic correlation to explain the discordant imaging findings.}, } @article {pmid29050179, year = {2017}, author = {Hua, B and Lu, X and Xiao, WZ and He, SR and Wang, Z}, title = {[The comparison of characters between invasive micropapillary carcinoma and invasive ductal carcinoma not otherwise specified of the breast].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {55}, number = {10}, pages = {770-774}, doi = {10.3760/cma.j.issn.0529-5815.2017.10.011}, pmid = {29050179}, issn = {0529-5815}, mesh = {Breast ; *Breast Neoplasms/diagnosis ; *Carcinoma, Ductal, Breast/diagnosis ; *Carcinoma, Papillary/diagnosis ; Disease-Free Survival ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; }, abstract = {Objective: To analyze the differences of clinicopathological characters and prognostic factors between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC) not otherwise specified of the breast. Methods: Patients who were treated from June 2008 to April 2016 in Breast Center of Beijing Hospital were retrospectively analyzed to evaluate the differences between IMPC (n=59) and IDC (n=1 080). Follow-up was done every 3 to 6 months postoperatively with a deadline of July 31, 2016. The curves of disease free survival (DFS) and overall survival (OS) were drawn by Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables which were identified on univariate analysis were analyzed with Cox's proportional hazards regression model for multivariate analysis. Results: More lymph nodes were involved in IMPC group (χ(2)=12.168, P=0.007) which led to more later stage in this group (χ(2)=8.950, P=0.011). IMPC group displayed a significantly increased rate of lymphovascular invasion (LVI) compared to IDC group (χ(2)=13.511, P = 0.001). The expression rate of estrogen receptor (ER) and progesterone receptor (PR) was higher in IMPC group than that in IDC group (89.8% vs. 76.3% and 88.1% vs. 70.7%, respectively, χ(2)=5.786, 8.332, all P<0.05). In multivariate analysis performed with the variables found significant in univariate analysis, the only variable found significantly affecting DFS of IMPC group was the T stage (T1-2 and T3-4, OR=5.217, 95%CI: 1.401 to 19.430, P=0.014), while in IDC group, pathological stage (stage Ⅰ to Ⅱ and stage Ⅲ to Ⅳ, OR=1.870, 95% CI: 1.262 to 2.771, P=0.002), lymph node positive ratio (LNR) (OR=2.222, 95%CI: 1.561 to 3.162, P=0.000), PR (OR=1.856, 95%CI: 1.118 to 3.082, P=0.017), and age (<50 years old and ≥50 years old, OR=0.695, 95%CI: 0.488 to 0.989, P=0.043) were prognostic factors. There were two variables found significantly affecting OS of IMPC group, which were T stage (OR=3.713, 95%CI: 1.539 to 8.959, P=0.004) and LNR (OR=2.850, 95%CI: 1.033 to 7.862, P=0.043). While in IDC group, LNR was the only variable found significantly affecting OS (OR=2.129, 95%CI: 1.324 to 3.425, P=0.002). Compared with IDC, the patients with IMPC were more likely to have local or regional recurrence (P=0.006). Although the median DFS interval was longer in IDC group (χ(2)=9.739, P=0.002), the median OS interval was comparable between the two groups (χ(2)=0.787, P=0.375). Conclusion: Although IMPC has lymphotropic feature, tendency of LVI and local or regional recurrence, it has an OS which is comparable with IDC.}, } @article {pmid29046750, year = {2017}, author = {Kliiger, J and Gorbaty, M}, title = {Metastasis to the pancreas and stomach from a breast cancer primary: a case report.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {7}, number = {4}, pages = {234-237}, pmid = {29046750}, issn = {2000-9666}, abstract = {A 60-year-old female with an unknown family history initially presented with signs and symptoms concerning for gastrointestinal cancer. Regular breast cancer screening and subsequent work-up around this time demonstrated the presence of T2N1 stage II triple positive ductal adenocarcinoma of the left breast. Follow-up imaging for her gastrointestinal symptoms demonstrated a 3.5 cm solitary mass in the pancreas and diffuse thickening of the stomach wall. Biopsies of the gastrointestinal lesions were identified as metastatic foci of the breast cancer primary. Breast cancer metastases to the stomach and to the pancreas are both very rare events. Of the breast cancer primaries that do metastasize to the gastrointestinal system, it is unusual for the primary to be ductal adenocarcinoma. The rapid succession of diagnosing the primary source of breast cancer simultaneously with its metastases is also unusual. Timely identification and appropriate management of these rare metastases was made possible due to routine breast cancer screening.}, } @article {pmid29045292, year = {2018}, author = {Bennett, JA and Young, RH and Chuang, AY and Lerwill, MF}, title = {Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases Including 14 Krukenberg Tumors.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {37}, number = {6}, pages = {507-515}, doi = {10.1097/PGP.0000000000000462}, pmid = {29045292}, issn = {1538-7151}, mesh = {Adenocarcinoma/*secondary ; Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Signet Ring Cell/*secondary ; Female ; Humans ; Krukenberg Tumor/*secondary ; Middle Aged ; Ovarian Neoplasms/*secondary ; }, abstract = {Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells, usually arises from the stomach but can also originate from other sites. We reviewed 17 metastatic breast carcinomas to the ovary with signet ring cells to potentially identify features indicative of mammary origin as opposed to other possible primary sites. The patients ranged from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3; adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to 284 (mean, 79) mo after the original diagnosis. Three patients had no known history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive lobular carcinoma, 1 had suspicious bilateral breast masses identified on imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the ovarian architecture was effaced in 71% by discrete tumor lobules separated by striking edema. The tumors exhibited a variety of histologic patterns: nests were most common (88%), followed by cords (82%), diffuse sheets (82%), single cells (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting the criteria for Krukenberg tumor. Signet ring cells were most frequently observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast origin, and the patterns recapitulate those seen in primary breast carcinomas. Features characteristic of gastrointestinal origin, such as extracellular mucin, intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid-like foci, were absent. The overall morphologic picture in cases of ovarian spread of breast cancer with signet ring cells is usually strongly suggestive of mammary origin. The diagnosis can be further supported by the clinical history and immunohistochemical evaluation.}, } @article {pmid29043992, year = {2017}, author = {Xu, J and Li, F and Chang, F}, title = {Correlation of the ultrasound imaging of breast cancer and the expression of molecular biological indexes.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {30}, number = {4(Suppl.)}, pages = {1425-1430}, pmid = {29043992}, issn = {1011-601X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/*diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/*diagnostic imaging/pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Predictive Value of Tests ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Tumor Burden ; *Ultrasonography, Mammary ; }, abstract = {This paper aims to 137 cases of breast malignant tumors confirmed by surgery and pathology were collected. All patients received ultrasound examination and were not treated by radiotherapy or chemotherapy before operation. The preoperative ultrasound images of breast cancer patients and postoperative pathological characteristics of paraffin sections were retrospectively observed. Ultrasound indicators included tumor size, shape, ratio of the longest/shortest dimension, edge of the spiculation and peripheral hyperechoic halo sign, internal echo types, micro calcification, posterior echo types, blood flow and signs of lymph node metastasis. The pathological indexes included histological type, infiltrating ductal carcinoma (IDC), histological grading, cancer tissue in the interior and edge of the lesion and stroma and expression of molecular biology indexes (ER, PR and C-erbB-2). The correlation of ultrasound imaging of breast cancer and his to pathological type and grading were analyzed and the ultrasounic characteristics and the his to pathological features was compared; then to explore the correlation of ultrasonic imaging of breast cancer and the expression of ER, PR and C-erbB-2. the tumor size of IDC (>2cm) was lager than that of the ductal carcinoma in situ (DCIS) and the early-stage IDC, with statistical significance (P<0.05), but compared with the specific carcinoma of breast (P>0.05). The ratio of irregular mass of IDC was more than that of the specific carcinoma of breast (P<0.05), but without statistical significance compared with the DCIS and early-stage IDC (P>0.05). The spiculate margin in the IDC was more than that of the early-stage IDC, DCIS and specific carcinoma of breast (P>0.05). The ratio of the longest/ shortest dimension, peripheral hyperechoic halo sign, internal echo, micro calfication, posterior echo types were not related to the types of breast cancer (P>0.05). The irregular mass rate in the III IDC were much higher than that in the I and II level IDC (P>0.05). The posterior echo attenuation in the I IDC was much higher than the II and III IDC (P>0.05). The tumor size, spiculate margin, peripheral hyperechoic halo, internal echo types, micro calcification were not significantly related to the histological grading of IDC. The tumor with larger size (>2cm), enhanced posterior echo, or lower internal echo will have a high histological classification and high rate of cancer tissue (P<0.05). The tumor with enhanced peripheral hyperechoic halo sign will have a higher histological classification and higher rate of cancer tissue in the peripheral tissues, compared with the tumors without halo (P<0.05). The tumor shape, ratio of the longest/ shortest dimension, spiculate margin were not significantly related to the internal tissues (P>0.05). The ratio of the longest/ shortest dimension (>1), spiculate margin and halo signs were related to the positive expression of ER and PR (P<0.05). The internal necrosis was related to the negative expression of PR, (P<0.05). The tumor size, shape, posterior echo types and blood flow were not significantly related to the expression of ER, PR and C-erbB-2 (P>0.05).}, } @article {pmid29043464, year = {2018}, author = {Mordang, JJ and Gubern-Mérida, A and Bria, A and Tortorella, F and Mann, RM and Broeders, MJM and den Heeten, GJ and Karssemeijer, N}, title = {The importance of early detection of calcifications associated with breast cancer in screening.}, journal = {Breast cancer research and treatment}, volume = {167}, number = {2}, pages = {451-458}, pmid = {29043464}, issn = {1573-7217}, support = {KUN 2012-5577//KWF Kankerbestrijding/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*complications/pathology ; Calcinosis/complications/*diagnosis/pathology ; *Early Diagnosis ; Female ; Humans ; Mammography ; Mass Screening ; Middle Aged ; }, abstract = {PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer.

METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined.

RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n = 177) of cancer-related calcifications that could have been detected earlier were associated with invasive cancer when diagnosed.

CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.}, } @article {pmid29037500, year = {2017}, author = {Siciliano, M and Trojano, L and De Micco, R and De Mase, A and Garramone, F and Russo, A and Tedeschi, G and Tessitore, A}, title = {Motor, behavioural, and cognitive correlates of fatigue in early, de novo Parkinson disease patients.}, journal = {Parkinsonism & related disorders}, volume = {45}, number = {}, pages = {63-68}, doi = {10.1016/j.parkreldis.2017.10.004}, pmid = {29037500}, issn = {1873-5126}, mesh = {Aged ; Anxiety/epidemiology/etiology ; Apathy ; Cognitive Dysfunction/epidemiology/etiology ; Fatigue/epidemiology/*etiology/*psychology ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications ; Prevalence ; Sleep Wake Disorders/epidemiology/etiology ; }, abstract = {INTRODUCTION: Fatigue is one of the most common and disabling non-motor symptoms in Parkinson's disease (PD). The objective of this study was to determine prevalence and motor, behavioural, and cognitive correlates of distressing fatigue in early, de novo PD patients.

METHODS: Eighty-one consecutive de novo PD patients (64% men; mean age 65.73 ± 8.26 years) underwent a comprehensive examination, including Parkinson's disease Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale (AES). Moreover, all patients underwent a detailed neuropsychological evaluation exploring attention and working memory, executive functions, memory, visuospatial abilities and language. Score of patients with or without distressing fatigue (defined as a PFS score ≥ 8) were compared by Student's t-test or Pearson's chi-square test. Logistic regression analyses were performed to search for motor and non-motor features independently associated with presence of distressing fatigue.

RESULTS: Twelve (15%) patients presented distressing fatigue. Logistic regression identified sleepiness (p = 0.04), "episodic anxiety" subscale of PAS (p = 0.005), and "cognitive apathy" subscale of AES (p = 0.017) as the main factors associated with distressing fatigue. No significant association was found between diagnosis of Mild Cognitive Impairment and distressing fatigue (p = 0.745).

CONCLUSION: In a sample of consecutive de novo PD patients, distressing fatigue is associated with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive impairment. Our findings suggest possible shared pathogenic mechanisms underlying these non-motor symptoms and foster development of early combined therapeutic approaches.}, } @article {pmid29033675, year = {2017}, author = {Köroğlu, R and Köksal, İ and Şimşek, FS and Gezer, F and Kekilli, E and Ünal, B}, title = {Considering the Relationship between Quantitative Parameters and Prognostic Factors in Breast Cancer: Can Mean Standardized Uptake Value be an Alternative to Maximum Standardized Uptake Value?.}, journal = {World journal of nuclear medicine}, volume = {16}, number = {4}, pages = {275-280}, pmid = {29033675}, issn = {1450-1147}, abstract = {It was aimed to investigate the correlation between maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and retention index (RI), which represents the quantitative evaluation of the uptake of [18]F-fluoro-2-deoxy-D-glucose ([18]F-FDG) used in positron emission tomography (PET) and clinicopathologic as well as biologic prognostic factors. Forty-one women with breast cancer who were histopathologically diagnosed were included in this study. Neoadjuvant chemotherapy was applied to all patients before PET/computed tomography (CT). After FDG injection, PET/CT screening was applied within the 1[st] h (PET-1) and in the 2[nd] h (PET-2). SUVmax, SUVmean, SUVmax RI, and SUVmean RI of every image were calculated qualitatively and semiquantitatively. The correlation between quantitative and semiquantitative PET parameters and biologic as well as clinicopathologic prognosis factors was evaluated. Statistically, significant positive correlation was found between lymph nodes (LNs), which were evaluated by clinical picture, clinical stage as well as histopathologically and quantitative PET parameters (SUVmax1, SUVmax2,, RImax, SUVmean1, SUVmean2, RImean) (P < 0.05). While statistically significant correlation with RImax was detected only by LN (histopathological), correlations with RImean were detected by clinical picture, clinical stage, metabolic stage, and LN (histopathological). Statistically, significant correlation was found between RImax and estrogen receptor in patients who were histopathologically diagnosed with invasive ductal carcinoma (n = 34) (P < 0.05). We detected correlations between biologic and clinicopathologic prognostic factors and SUVmax as well as SUVmean values in breast carcinoma. SUVmean values may provide important knowledge when the correlation between prognostic factors and PET parameters is investigated even if they are not used routinely.}, } @article {pmid29032166, year = {2018}, author = {Shenkman, G and Shrira, A and Ifrah, K and Shmotkin, D}, title = {Interpersonal vulnerability among offspring of Holocaust survivors gay men and its association with depressive symptoms and life satisfaction.}, journal = {Psychiatry research}, volume = {259}, number = {}, pages = {89-94}, doi = {10.1016/j.psychres.2017.10.017}, pmid = {29032166}, issn = {1872-7123}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child of Impaired Parents/*psychology ; Depression/diagnosis/*psychology ; Holocaust/*psychology/trends ; Humans ; Male ; Middle Aged ; *Personal Satisfaction ; Personality Tests/standards ; Self Report/standards ; Sexual and Gender Minorities/*psychology ; Survivors/*psychology ; Young Adult ; }, abstract = {The aim of the current study was to examine whether offspring of Holocaust survivors (OHS) gay men report higher interpersonal vulnerability in comparison to non-OHS gay men, and to further assess whether that vulnerability mediates the association between having a Holocaust background and mental health outcomes (depressive symptoms and life satisfaction). For this purpose, a community-dwelling sample of 79 middle-aged and older OHS and 129 non-OHS gay men completed measures of hostile-world scenario (HWS) in the interpersonal domain, satisfaction from current steady relationship, depressive symptoms and life satisfaction. Results indicated that OHS reported higher HWS interpersonal vulnerability and lower satisfaction from current relationship in comparison to non-OHS gay men. Also, having a Holocaust background had an indirect effect on depressive symptoms and life satisfaction through HWS interpersonal vulnerability as well as through satisfaction from current relationship. These findings are the first to suggest interpersonal vulnerability of older OHS, in comparison to non-OHS, gay men, and an association between this vulnerability and adverse psychological outcomes. This interpersonal vulnerability, possibly representing HWS threats of both early family-based trauma and current sexual minority stress, along with its implications, should be addressed by practitioners who work with older gay men having a Holocaust background.}, } @article {pmid29030299, year = {2017}, author = {Rozengurt, R and Shtoots, L and Sheriff, A and Sadka, O and Levy, DA}, title = {Enhancing early consolidation of human episodic memory by theta EEG neurofeedback.}, journal = {Neurobiology of learning and memory}, volume = {145}, number = {}, pages = {165-171}, doi = {10.1016/j.nlm.2017.10.005}, pmid = {29030299}, issn = {1095-9564}, mesh = {Adult ; Brain/*physiology ; Electroencephalography ; Female ; Humans ; Male ; Memory Consolidation/*physiology ; *Memory, Episodic ; Mental Recall/physiology ; *Neurofeedback ; *Theta Rhythm ; }, abstract = {Consolidation of newly formed memories is readily disrupted, but can it be enhanced? Given the prominent role of hippocampal theta oscillations in memory formation and retrieval, we hypothesized that upregulating theta power during early stages of consolidation might benefit memory stability and persistence. We used EEG neurofeedback to enable participants to selectively increase theta power in their EEG spectra following episodic memory encoding, while other participants engaged in low beta-focused neurofeedback or passively viewed a neutral nature movie. Free recall assessments immediately following the interventions, 24h later and 7d later all indicated benefit to memory of theta neurofeedback, relative to low beta neurofeedback or passive movie-viewing control conditions. The degree of benefit to memory was correlated with the extent of theta power modulation, but not with other spectral changes. Theta enhancement may provide optimal conditions for stabilization of new hippocampus-dependent memories.}, } @article {pmid29026955, year = {2018}, author = {Watson, L and Dunn, D and Fraser-Kirk, G}, title = {Indolent Rib Osteomyelitis Following Breast Implant Reconstruction: An Unusual Case and Review of the Literature.}, journal = {Aesthetic plastic surgery}, volume = {42}, number = {2}, pages = {447-450}, doi = {10.1007/s00266-017-0975-z}, pmid = {29026955}, issn = {1432-5241}, mesh = {Anti-Bacterial Agents/therapeutic use ; Australia ; Breast Implantation/*adverse effects/methods ; Breast Implants/*adverse effects ; Breast Neoplasms/pathology/*surgery ; Device Removal ; Female ; Follow-Up Studies ; Humans ; Mastectomy/methods ; Middle Aged ; Osteomyelitis/drug therapy/*etiology/physiopathology ; Prosthesis-Related Infections/diagnosis/microbiology/*surgery ; Rare Diseases ; Ribs/*microbiology/pathology ; Risk Assessment ; Treatment Outcome ; }, abstract = {UNLABELLED: Rib osteomyelitis is an infrequently occurring but important complication of breast implant surgery. Although prosthetic or surgical site infection (SSI) and rib osteomyelitis as separate entities are well described in the literature, only five cases of rib or sternal osteomyelitis related to implant placement have been reported globally. Historically patients who experience this complication have not demonstrated an identifiable prevalence of the traditional risk factors associated with SSI or rib osteomyelitis. This report describes the sequence of clinical manifestations of an unusual case of breast implants complicated by rib osteomyelitis. A 56-year-old female underwent mastectomy and insertion of tissue expanders for bilateral invasive ductal carcinoma following which the tissue expanders became infected in the early postoperative period and were subsequently removed. The patient underwent successful expander insertion and subsequent implant exchange surgery several years later and enjoyed an uncomplicated recovery from this. Following nipple reconstruction more than 12 months after successful implant placement, she presented with Staphylococcus epidermidis bacteremia and a left-sided clinical peri-implant infection. Upon removal of her implant, an intraoperative discovery of rib necrosis/osteomyelitis was made for which she was treated. To provide context, the literature was reviewed for other reported cases of rib osteomyelitis following breast implant surgery. This patient, in combination with others reported in the literature, emphasises the diagnostic difficulties posed by this condition as a result of its low incidence and variable or absent clinical features.

LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .}, } @article {pmid28993866, year = {2018}, author = {Stuebs, F and Heidemann, S and Caliebe, A and Mundhenke, C and Arnold, N}, title = {CDH1 mutation screen in a BRCA1/2-negative familial breast-/ovarian cancer cohort.}, journal = {Archives of gynecology and obstetrics}, volume = {297}, number = {1}, pages = {147-152}, doi = {10.1007/s00404-017-4551-1}, pmid = {28993866}, issn = {1432-0711}, mesh = {Adult ; Antigens, CD/*metabolism ; BRCA1 Protein/*metabolism ; BRCA2 Protein/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/*metabolism ; Cohort Studies ; Early Detection of Cancer ; Female ; Genetic Predisposition to Disease ; Humans ; Mutation ; Ovarian Neoplasms/*genetics/pathology ; }, abstract = {PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC).

METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results.

RESULTS: In total, we found two potentially pathogenic CDH1 alterations, c.1774G > A, pAla592Thr, and c.2512 A > G, p.Ser838Gly, classified as variants of unknown significance according to ClinVar. In addition, we detected a high number of known CDH1 polymorphisms (n = 62), some of them more frequent in patients with lobular (55%) than in those with invasive ductal carcinoma (27%).

CONCLUSION: Although none of the probands studied carried a clearly pathogenic CDH1 mutation, CDH1 could be considered a potential breast cancer gene, esp. for ILC worth including it in the NGS (next generation sequencing) HBOC panel.}, } @article {pmid28990825, year = {2018}, author = {Shelef, L and Brunstein Klomek, A and Yavnai, N and Shahar, G}, title = {Perceived Stress and Intent to Die in Young Soldiers Who Attempt Suicide.}, journal = {Crisis}, volume = {39}, number = {2}, pages = {144-148}, doi = {10.1027/0227-5910/a000481}, pmid = {28990825}, issn = {2151-2396}, mesh = {Adolescent ; Cross-Sectional Studies ; Depression/*psychology ; Female ; Humans ; *Intention ; Male ; Military Personnel/*psychology ; Perception ; Stress, Psychological/*psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Young Adult ; }, abstract = {BACKGROUND: Intent to die is an important component of suicide risk assessment. The authors compared the predictive effect of two forms of stress - military and perceived - in intent to die by suicide among young adult Israeli soldiers with a history of suicide attempts. Depression, suicide ideation, and habituation/acquired capacity for suicidality served as covariates.

METHODS: Participants were 60 young adult soldiers in the Israeli Defense Force (ISF; aged 18-21 years), who made a suicide attempt during their military service. Study variables were assessed using self-report measures.

RESULTS: Intent to die by suicide correlated with suicide ideation, habituation/acquired capacity, depressive symptoms, and perceived stress. In a multiple regression analysis, perceived stress predicted intent to die (b = .44, p = .002) over and above the prediction by suicide ideation (b = .42, p = .013) and acquired capacity/habituation (b = .28, p = .023).

LIMITATIONS: The cross-sectional design restricts causal inference. In addition, an exclusive reliance on self-report measures might have inflated shared method variance.

CONCLUSIONS: Perceived stress captures a unique dimension of intent to die by suicide among young suicide attempters.}, } @article {pmid28982860, year = {2017}, author = {Grzegrzolka, J and Wojtyra, P and Biala, M and Piotrowska, A and Gomulkiewicz, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P}, title = {Correlation Between Expression of Twist and Podoplanin in Ductal Breast Carcinoma.}, journal = {Anticancer research}, volume = {37}, number = {10}, pages = {5485-5493}, doi = {10.21873/anticanres.11978}, pmid = {28982860}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/mortality/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/mortality/surgery ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Glycoproteins/*analysis/genetics ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Stromal Cells/chemistry/pathology ; Time Factors ; Treatment Outcome ; Twist-Related Protein 1/*analysis/genetics ; Up-Regulation ; }, abstract = {BACKGROUND/AIM: As a result of activation of transcription factors engaged in epithelial-mesenchymal transition (EMT), such as Twist, inhibition of epithelial markers and an increased expression of mesenchymal markers are observed. One of the specific markers of cancer-associated fibroblasts is podoplanin (PDPN) - a mucin-type membrane glycoprotein. The aim of this work was to study the localisation and intensity of expression of Twist and PDPN on the mRNA and protein level in cases of invasive ductal breast carcinoma (IDC), and its association with patients' clinico-pathological data.

MATERIALS AND METHODS: The study included archival material in a form of 80 paraffin IDC blocks and 11 IDC fragments frozen in liquid nitrogen. Immunohistochemical expression of Twist and PDPN was evaluated using light microscope and semiquantitative scale for evaluation of nuclear expression or immunoreactive scale (IRS) for evaluation of cytoplasmic expression. Material was isolated from frozen IDC fragments using laser micro-dissection (from cancer and stromal cells, separately) and was used to perform real-time PCR.

RESULTS: Twist expression was higher in stromal cells in comparison to cancer cells. Analysis of patients' survival rate showed, that higher expression of Twist in cancer cells was associated with shorter overall survival time and shorter event-free survival time. The expression of PDPN was also higher in stromal cells in comparison with cancer cells. In addition, positive correlation was observed between expression of Twist and PDPN in stromal cells of IDC (r=0.267; p<0.05).

CONCLUSION: The relationship between the higher expression of Twist in both cancer and stromal cells and shorter patients' survival indicates Twist as a potential useful prognostic marker in IDC. Positive correlation of Twist and PDPN expression may indicate the role of PDPN in EMT in IDC.}, } @article {pmid28977728, year = {2018}, author = {Porter, LH and Hashimoto, K and Lawrence, MG and Pezaro, C and Clouston, D and Wang, H and Papargiris, M and Thorne, H and Li, J and , and Ryan, A and Norden, S and Moon, D and Bolton, DM and Sengupta, S and Frydenberg, M and Murphy, DG and Risbridger, GP and Taylor, RA}, title = {Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells.}, journal = {BJU international}, volume = {121}, number = {6}, pages = {971-978}, doi = {10.1111/bju.14043}, pmid = {28977728}, issn = {1464-410X}, mesh = {Adenocarcinoma/pathology ; Aged ; Aged, 80 and over ; Androgen Antagonists/*therapeutic use ; Animals ; Carcinoma, Ductal/*drug therapy/pathology ; Heterografts/pathology ; Humans ; Kaplan-Meier Estimate ; Male ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/*drug therapy/pathology ; Retrospective Studies ; Transplantation, Heterologous ; Xenograft Model Antitumor Assays/methods ; }, abstract = {OBJECTIVE: To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT).

MATERIALS AND METHODS: We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts.

RESULTS: We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration.

CONCLUSION: The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.}, } @article {pmid28977635, year = {2017}, author = {Kumar, V and Fleming, T and Terjung, S and Gorzelanny, C and Gebhardt, C and Agrawal, R and Mall, MA and Ranzinger, J and Zeier, M and Madhusudhan, T and Ranjan, S and Isermann, B and Liesz, A and Deshpande, D and Häring, HU and Biswas, SK and Reynolds, PR and Hammes, HP and Peperkok, R and Angel, P and Herzig, S and Nawroth, PP}, title = {Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair.}, journal = {Nucleic acids research}, volume = {45}, number = {18}, pages = {10595-10613}, pmid = {28977635}, issn = {1362-4962}, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/*metabolism ; Cell Nucleus/enzymology/metabolism ; Cellular Senescence ; DNA/metabolism ; DNA Breaks, Double-Stranded ; *DNA Repair ; DNA Repair Enzymes/metabolism ; DNA-Binding Proteins/metabolism ; Homeostasis ; Lung/physiopathology ; MRE11 Homologue Protein ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Fibrosis/genetics/physiopathology ; Receptor for Advanced Glycation End Products/genetics/*metabolism ; Reperfusion Injury/genetics/metabolism ; Signal Transduction ; }, abstract = {The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.}, } @article {pmid28975495, year = {2018}, author = {Flood, TA and Schieda, N and Sim, J and Breau, RH and Morash, C and Belanger, EC and Robertson, SJ}, title = {Evaluation of tumor morphologies and association with biochemical recurrence after radical prostatectomy in grade group 5 prostate cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {472}, number = {2}, pages = {205-212}, pmid = {28975495}, issn = {1432-2307}, mesh = {Adenocarcinoma/*pathology/surgery ; Aged ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis/*pathology ; *Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {We assessed Gleason pattern 5 (GP5) and other prostatic adenocarcinoma (PCa) morphologies to determine their association with biochemical recurrence (BCR). A search for grade group 5 PCa with radical prostatectomy (RP) yielded 49 patients. RPs were reviewed for %GP5 and morphologies (sheets, single cells, cords, small solid cylinders, solid medium to large nests with rosette-like spaces [SMLNRS], comedonecrosis, cribriform glands, glomerulations, intraductal carcinoma of the prostate [IDC-P], and prostatic ductal adenocarcinoma [PDCa]). Prevalence of morphologies was as follows: single cells 100%, cribriform glands 98.7%, cords 85.7%, IDC-P 77.6%, comedonecrosis 53.1%, sheets 49.0%, small solid cylinders 49.0%, PDCa 44.9%, glomerulations 34.7%, and SMLNRS 14.3%. From 28 patients who were treated with RP as monotherapy, 64.3% (18/28) had BCR. Comedonecrosis, sheets, small solid cylinders, IDC-P, and PDCa were significantly associated with BCR. Number of morphologies on RP and %GP5 were higher in patients with BCR (6.8 ± 2.1 versus 3.7 ± 2.9%; P < 0.001 and 26.9 ± 16.8 versus 11.4 ± 14.1%; P = 0.02) with area under ROC curve of 0.89 (confidence intervals [CI] 0.77-1.00). Sensitivity/specificity was 77.8/80.0% for predicting BCR when ≥ 5 morphologies were present and 0.79 (CI 0.60-0.99) with sensitivity/specificity of 66.7/80.0% for predicting BCR when ≥ 15% GP5 was present. Hazard ratio for BCR was higher with increasing number of morphologies (1.23, CI 1.02-1.49; P = 0.034) but not %GP5 (0.99, CI 0.97-1.02, P = 0.622). Our results indicate that GP5 morphologies may represent a biologically heterogeneous group and that an increasing number of PCa morphologies on RP is strongly associated with an increased risk of BCR.}, } @article {pmid28974441, year = {2017}, author = {Kim, YY and Lee, S and Kim, MJ and Kang, BC and Dhakal, H and Choi, YA and Park, PH and Choi, H and Shin, TY and Choi, HG and Kwon, TK and Khang, D and Kim, SH}, title = {Tyrosol attenuates lipopolysaccharide-induced acute lung injury by inhibiting the inflammatory response and maintaining the alveolar capillary barrier.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {109}, number = {Pt 1}, pages = {526-533}, doi = {10.1016/j.fct.2017.09.053}, pmid = {28974441}, issn = {1873-6351}, mesh = {Acute Lung Injury/*drug therapy/etiology/genetics/*immunology ; Animals ; Cyclooxygenase 2/genetics/immunology ; Cytokines/genetics/immunology ; Humans ; Interleukin-6/genetics/immunology ; Lipopolysaccharides/adverse effects ; Lung/immunology/pathology ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B/genetics/immunology ; Nitric Oxide Synthase Type II/genetics/immunology ; Phenylethyl Alcohol/administration & dosage/*analogs & derivatives ; Pulmonary Alveoli/drug effects/immunology ; Signal Transduction/drug effects ; }, abstract = {Acute lung injury (ALI) is a life-threatening disease characterized by increased pulmonary vascular permeability because of alveolar capillary barrier dysfunction and increased immune responses. This study determined the anti-inflammatory effect of tyrosol on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms of action. BALB/c mice were orally administered with tyrosol (0.1, 1, and 10 mg/kg) 1 h before an intratracheal injection of LPS (25 μg/50 μL). Oral treatment with tyrosol inhibited lung vascular permeability, histopathological changes, wet/dry lung weight ratio, and pulmonary vascular cell infiltration. The LPS-induced imbalance in the activity of enzymes, such as superoxide dismutase and myeloperoxidase, was regulated by tyrosol. Pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, were reduced by tyrosol in bronchoalveolar lavage fluid and lung tissue. The activation of inflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated-IκBα, was suppressed by the presence of tyrosol in the lung tissue. In addition, tyrosol attenuated the production of NO, the expression of pro-inflammatory cytokines, the expression of iNOS and COX-2, and the nuclear translocation of nuclear factor-κB in LPS-stimulated RAW 264.7 macrophages. These results suggested that tyrosol is a potential therapeutic agent for treating inflammatory lung diseases.}, } @article {pmid28972249, year = {2016}, author = {El Amine, O and Ouni, R and Adouni, O and Goucha, A and Ben Hassouna, J and Rahal, K and El May, A and Gamoudi, A}, title = {Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.}, journal = {La Tunisie medicale}, volume = {94}, number = {10}, pages = {587-593}, pmid = {28972249}, issn = {0041-4131}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; *Cell Proliferation ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Middle Aged ; *Mitotic Index ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle.

AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker.

METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method.

RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score.

CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.}, } @article {pmid28970859, year = {2017}, author = {Oh, SW and Lim, HS and Lee, JS and Moon, SM and Park, MH}, title = {Invasive Micropapillary Carcinoma in Axillary Ectopic Breast and Synchronous Ductal Carcinoma In Situ in the Contralateral Breast.}, journal = {Journal of breast cancer}, volume = {20}, number = {3}, pages = {314-318}, pmid = {28970859}, issn = {1738-6756}, abstract = {The development of ectopic breast tissue is attributable to the failure of primitive mammary tissue to regress after the development of the mammary ridge, except at pectoral breast sites, and is most often evident in the axillae. Several benign and malignant breast diseases have been reported in ectopic axillary breast tissues. The most common cancerous pathology of ectopic breast tissue is invasive ductal carcinoma. Ectopic breast cancer presenting with simultaneous primary cancer of the pectoral breast is extremely rare. Herein, we report an invasive micropapillary carcinoma of an axillary ectopic breast, combined with a synchronous ductal carcinoma in situ in the contralateral pectoral breast of a 61-year-old woman.}, } @article {pmid28970852, year = {2017}, author = {Kim, YG and Jeon, YW and Ko, BK and Sohn, G and Kim, EK and Moon, BI and Youn, HJ and Kim, HA and , }, title = {Clinicopathologic Characteristics of Pregnancy-Associated Breast Cancer: Results of Analysis of a Nationwide Breast Cancer Registry Database.}, journal = {Journal of breast cancer}, volume = {20}, number = {3}, pages = {264-269}, pmid = {28970852}, issn = {1738-6756}, abstract = {PURPOSE: This study aimed to evaluate the clinicopathological characteristics of pregnancy-associated breast cancer (PABC) in comparison with non-pregnancy associated breast cancer (non-PABC).

METHODS: A total of 344 eligible patients with PABC were identified in the Korean Breast Cancer Society Registry database. PABC was defined as ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma diagnosed during pregnancy or within 1 year after the birth of a child. Patients with non-PABC were selected from the same database using a 1:2 matching method. The matching variables were operation, age, and initial stage.

RESULTS: Patients with PABC had significantly lower survival rates than patient with non-PABC (10-year survival rate: PABC, 76.4%; non-PABC, 85.1%; p=0.011). PABC patients had higher histologic grade and were more frequently hormone receptor negative than non-PABC patients. Being overweight (body mass index [BMI], ≥23 kg/m[2]), early menarche (≤13 years), late age at first childbirth (≥30 years), and a family history of breast cancer were more common in the PABC group than in the non-PABC group. Multivariate analysis showed the following factors to be significantly associated with PABC (vs. non-PABC): early menarche (odds ratio [OR], 2.165; 95% confidence interval [CI], 1.566-2.994; p<0.001), late age at first childbirth (OR, 2.446; 95% CI, 1.722-3.473; p<0.001), and being overweight (OR, 1.389; 95% CI, 1.007-1.917; p=0.045).

CONCLUSION: Early menarche, late age at first childbirth, and BMI ≥23 kg/m[2] were more associated with PABC than non-PABC.}, } @article {pmid28969261, year = {2017}, author = {Ghosh, M and Muneer, A and Trivedi, V and Mandal, K and Shubham, S}, title = {Metaplastic Carcinoma Breast: A Clinical Analysis of Nine Cases.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {11}, number = {8}, pages = {XR01-XR03}, pmid = {28969261}, issn = {2249-782X}, abstract = {Metaplastic Breast Carcinoma (MBC) is a rare heterogeneous group of primary breast malignancies with different subgroups; exhibits a variety of histopathologic patterns and appears to be both epithelial and mesenchymal in origin. The ideal treatment for MBC remains unknown, due to its low incidence and pathological variability. Owing to its rarity, MBC has been treated as a variant of Invasive Duct Carcinoma (IDC). But it has poorer prognosis as compared to IDC. This is a case series to evaluate clinicopathologic characteristics and the multi-disciplinary treatment of nine MBC patients treated in a single institute.}, } @article {pmid28967088, year = {2017}, author = {Cavalieri, S and Stathis, A and Fabbri, A and Sonzogni, A and Perrone, F and Tamborini, E and Pelosi, G and de Braud, F and Platania, M}, title = {Uncommon somatic mutations in metastatic NUT midline carcinoma.}, journal = {Tumori}, volume = {103}, number = {Suppl. 1}, pages = {e5-e8}, doi = {10.5301/tj.5000685}, pmid = {28967088}, issn = {2038-2529}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; DCC Receptor/genetics ; DNA-Binding Proteins/genetics ; Fatal Outcome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; *Mutation ; Neoplasm Proteins ; Nuclear Proteins/*genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; RNA Splicing Factors/genetics ; }, abstract = {INTRODUCTION:: NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT.

CASE PRESENTATION:: We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years.

CONCLUSIONS:: To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.}, } @article {pmid28966860, year = {2017}, author = {Zhao, Y and Burger, WR and Zhou, M and Bernhardt, EB and Kaufman, PA and Patel, RR and Angeles, CV and Pogue, BW and Paulsen, KD and Jiang, S}, title = {Collagen quantification in breast tissue using a 12-wavelength near infrared spectral tomography (NIRST) system.}, journal = {Biomedical optics express}, volume = {8}, number = {9}, pages = {4217-4229}, pmid = {28966860}, issn = {2156-7085}, support = {R01 CA176086/CA/NCI NIH HHS/United States ; }, abstract = {A portable near infrared spectral tomography (NIRST) system was adapted for breast cancer detection and treatment monitoring with improved speed of acquisition for parallel 12 wavelengths of parallel frequency-domain (FD) and continuous-wavelength (CW) measurement. Using a novel gain adjustment scheme in the Photomultiplier Tube detectors (PMTs), the data acquisition time for simultaneous acquisition involving three FD and three CW wavelengths, has been reduced from 90 to 55 seconds, while signal variation was also reduced from 2.1% to 1.1%. Tomographic images of breast collagen content have been recovered for the first time, and image reconstruction approaches with and without collagen content included have been validated in simulation studies and normal subject exams. Simulations indicate that including collagen content into the reconstruction procedure can significantly reduce the overestimation in total hemoglobin, water and lipid by 8.9μM, 1.8% and 15.8%, respectively, and underestimates in oxygen saturation by 9.5%, given an average 10% background collagen content. A breast cancer patient with invasive ductal carcinoma was imaged and the reconstructed images show that the recovered tumor/background contrast in total hemoglobin increased from 1.5 to 1.7 when collagen was included in reconstruction.}, } @article {pmid28958942, year = {2017}, author = {Jensen, HH and Login, FH and Park, JY and Kwon, TH and Nejsum, LN}, title = {Immunohistochemical evalulation of activated Ras and Rac1 as potential downstream effectors of aquaporin-5 in breast cancer in vivo.}, journal = {Biochemical and biophysical research communications}, volume = {493}, number = {3}, pages = {1210-1216}, doi = {10.1016/j.bbrc.2017.09.125}, pmid = {28958942}, issn = {1090-2104}, mesh = {Aquaporin 5/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Signal Transduction ; rac1 GTP-Binding Protein/*metabolism ; ras Proteins/*metabolism ; }, abstract = {Aberrant levels of aquaporin-5 (AQP5) expression have been observed in several types of cancer, including breast cancer, where AQP5 overexpression is associated with metastasis and poor prognosis. In cultured cancer cells, AQP5 facilitates cell migration and activates Ras signaling. Both increased cell migration and Ras activation are associated with cancer metastasis, but so far it is unknown if AQP5 also affects these processes in vivo. Therefore, we investigated if high AQP5 expression in breast cancer tissue correlated with increased activation of Ras and of Rac1, which is a GTPase also involved in cell migration. This was accomplished by immunohistochemical analysis of invasive ductal carcinoma of breast tissue sections from human patients, followed by qualitative and quantitative correlation analysis between AQP5 and activated Ras and Rac1. Immunohistochemistry revealed that activation of Ras and Rac1 was positively correlated. There was, however, no correlation between high AQP5 expression and activation of Ras, whereas a nonsignificant, but positive, tendency between the levels of AQP5 and activated Rac1 levels was observed. In summary, this is the first report that correlates AQP5 expression levels to downstream signaling partners in breast cancer tissue sections. The results suggest Rac1 as a potential downstream signaling partner of AQP5 in vivo.}, } @article {pmid28956674, year = {2017}, author = {Yu, J and Pincus, K and Mattingly, TJ}, title = {Service description and analysis for an interprofessional discharge clinic within a primary care practice.}, journal = {Journal of interprofessional care}, volume = {31}, number = {6}, pages = {771-773}, doi = {10.1080/13561820.2017.1347611}, pmid = {28956674}, issn = {1469-9567}, mesh = {Adolescent ; Adult ; Aged ; Ambulatory Care Facilities/organization & administration ; Continuity of Patient Care/*organization & administration ; Cooperative Behavior ; Electronic Health Records ; Female ; Humans ; *Interprofessional Relations ; Male ; Medication Reconciliation/organization & administration/statistics & numerical data ; Middle Aged ; Patient Care Team/*organization & administration ; *Patient Discharge ; Patient Readmission/*statistics & numerical data ; Primary Health Care/*organization & administration ; Retrospective Studies ; Socioeconomic Factors ; Young Adult ; }, abstract = {At care transitions, patients are susceptible to adverse events and medication errors that can lead to harm or hospital readmission. This study describes the services provided by an interprofessional discharge clinic (IDC) aimed to improve these transitions and the impact on 30-day readmission rate, medication errors, and interventions documented. Data were collected retrospectively using an electronic medical record and analysed using SAS data system. Among 167 discharged patients, 154 patients were seen by a physician only (PO) and 13 patients were seen in the IDC. Thirty-day readmission rates were 26.6% and 7.7% for patients in the PO and IDC groups, respectively (p = 0.19). Seventy patients (45.5%) in the PO group and 11 patients (84.6%) in the IDC group (p = 0.0082) were found to have at least one medication error. All patients seen at the IDC had an intervention made, while 68 (44.2%) seen by a PO received no intervention (p = 0.0009). While sample size was a major limitation, a statistically significant increase in identified medication errors and intervention documentation was found in the IDC group. It is critical that healthcare systems continue to develop new strategies, such as IDCs, to reduce hospital readmissions.}, } @article {pmid28955367, year = {2017}, author = {Boamponsem, GA and Leung, DWM and Lister, C}, title = {Insights into Resistance to Fe Deficiency Stress from a Comparative Study of In Vitro-Selected Novel Fe-Efficient and Fe-Inefficient Potato Plants.}, journal = {Frontiers in plant science}, volume = {8}, number = {}, pages = {1581}, pmid = {28955367}, issn = {1664-462X}, abstract = {Iron (Fe) deficiency induces chlorosis (IDC) in plants and can result in reduced plant productivity. Therefore, development of Fe-efficient plants is of great interest. To gain a better understanding of the physiology of Fe-efficient plants, putative novel plant variants were regenerated from potato (Solanum tubersosum L. var. 'Iwa') callus cultures selected under Fe deficient or low Fe supply (0-5 μM Fe). Based on visual chlorosis rating (VCR), 23% of callus-derived regenerants were classified as Fe-efficient (EF) and 77% as Fe-inefficient (IFN) plant lines when they were grown under Fe deficiency conditions. Stem height was found to be highly correlated with internodal distance, leaf and root lengths in the EF plant lines grown under Fe deficiency conditions. In addition, compared to the IFN plant lines and control parental biotype, the EF plants including the lines named A1, B2, and B9, exhibited enhanced formation of lateral roots and root hairs as well as increased expression of ferritin (fer3) in the leaf and iron-regulated transporter (irt1) in the root. These morphological adaptations and changes in expression the fer3 and irt1 genes of the selected EF potato lines suggest that they are associated with resistance to low Fe supply stress.}, } @article {pmid28954989, year = {2017}, author = {Nozoe, T and Nozoe, E and Kono, M and Ohga, T and Ezaki, T}, title = {Further evidence to demonstrate the significance of serum appearance of anti-p53 antibody as a marker for progressive potential in invasive ductal carcinoma of the breast.}, journal = {The journal of medical investigation : JMI}, volume = {64}, number = {3.4}, pages = {241-244}, doi = {10.2152/jmi.64.241}, pmid = {28954989}, issn = {1349-6867}, mesh = {Adult ; Aged ; Antibodies/*blood ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*pathology ; Carcinoma, Ductal, Breast/blood/*pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tumor Suppressor Protein p53/*immunology ; }, abstract = {BACKGROUND: Serum appearance of anti-p53 antibody (p53Ab) has been reported as an indicator for progressive potential of human tumor tumors including breast cancer. But its significance in breast cancer has not been discussed fully.

METHODS: Relationship between serum appearance of p53Abs and representative data accounting for progressive potential in breast cancer, nuclear grade (NG), triple negative cancer, and the cumulative score based on these two data (TGS) was investigated among 129 women with invasive ductal carcinoma (IDC) of the breast, who had been treated with surgical resection.

RESULTS: There was a significant correlation between appearance of p53Abs and recurrence of the tumors (P = 0.035). Significant correlation of serum appearance of p53Abs with negative expression of ER (P = 0.011), the proportion of TNBC (P = 0.013), NG (P = 0.017), and TGS (P = 0.0005).

CONCLUSIONS: Preoperative serum appearance of p53Abs can be correlated with pathological nuclear grade, incidence of triple negative breast cancer, and TGS. These results might demonstrate more powerful significance of serum appearance of p53Abs as an indicator of progressive potential in IDC of the breast. J. Med. Invest. 64: 241-244, August, 2017.}, } @article {pmid28950981, year = {2017}, author = {Halperin, E and Tagar, MR}, title = {Emotions in conflicts: understanding emotional processes sheds light on the nature and potential resolution of intractable conflicts.}, journal = {Current opinion in psychology}, volume = {17}, number = {}, pages = {94-98}, doi = {10.1016/j.copsyc.2017.06.017}, pmid = {28950981}, issn = {2352-2518}, mesh = {*Conflict, Psychological ; *Emotions ; Humans ; Negotiating/*psychology ; }, abstract = {In recent years, researchers have been making substantial advances in understanding the central role of emotions in intractable conflict. We now know that discrete emotions uniquely shape policy preferences in conflict through their unique emotional goals and action tendencies in all stages of conflict including conflict management, conflict resolution and reconciliation. Drawing on this understanding, recent research also points to emotion regulation as a path to reduce conflict and advance peace, exploring both direct and indirect strategies of emotion regulation.}, } @article {pmid28944120, year = {2017}, author = {Saha, D and Tannenbaum, S and Zhu, Q}, title = {Treatment of Male Breast Cancer by Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade and Response Prediction Using Novel Optical Tomography Imaging: A Case Report.}, journal = {Cureus}, volume = {9}, number = {7}, pages = {e1481}, pmid = {28944120}, issn = {2168-8184}, support = {R01 EB002136/EB/NIBIB NIH HHS/United States ; }, abstract = {Male breast cancer, although rare, is on the rise. Prospective clinical trials are unlikely and current management mirrors that of post-menopausal women. Neoadjuvant chemotherapy is widely used and pathologic complete response (pCR) predicts long-term survival. The addition of dual HER2 (human epidermal growth factor receptor 2) blockade has shown the highest pCR rates; however, there is no published data of this approach in men. Also, newer monitoring tools are necessary during a neoadjuvant therapy to help personalize treatment. Here, we describe the case of a 64-year-old man with Stage IIB (tumor size 2 to 5 cm with involvement of axillary lymph nodes), high-grade estrogen receptor, progesterone receptor, and HER2-positive invasive ductal carcinoma with a germline breast cancer susceptibility gene 1 (BRCA1) mutation who was treated in a neoadjuvant fashion with dual HER2 blockade and platinum-based chemotherapy regimen. A novel predictive tool, ultrasound-localized diffuse optical tomography, was used to monitor his progress during treatment.}, } @article {pmid28943920, year = {2017}, author = {Nakashoji, A and Matsui, A and Nagayama, A and Iwata, Y and Sasahara, M and Murata, Y}, title = {Clinical predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4135-4141}, pmid = {28943920}, issn = {1792-1074}, abstract = {The response of triple-negative breast cancer (TNBC) to chemotherapy is heterogeneous; particular subtype classifications based on mRNA gene expression analysis have been demonstrated to be associated with a pathological complete response (pCR). The aim of the present study was to investigate additional clinical and pathological characteristics associated with pCR status. The pathological and clinical characteristics of 40 TNBC patients who underwent neoadjuvant chemotherapy followed by surgery were retrospectively analyzed by dividing the cases into two groups according to the response to treatment: pCR (n=12) and non-pCR (n=28). Clinically, patients in the pCR group presented tumors with a significantly less advanced Tumor-Node-Metastasis stage (P=0.030) and mammographic calcification was less common (17 vs. 58%; P=0.034). Pathologically, whereas all cases in the pCR group (12/12, 100%) were of the histological type 'invasive ductal carcinoma, not otherwise specified' (IDC-NOS), the non-pCR group consisted of a lower proportion of IDC-NOS cases (20/28, 71%) and more cases of special histological types, including mucinous, metaplastic, medullary and apocrine carcinomas (P=0.079). The positive rates of androgen receptor (AR) and forkhead-box A1 (FOXA1) tended to be lower in the pCR group (AR, 0 vs. 29%, P=0.079; FOXA1, 8 vs. 29%, P=0.233). The Ki-67 score was significantly higher in the pCR group than in the non-pCR group (P=0.041). The results suggest that patients with TNBC who present with clinically less advanced tumors and less frequent mammographic calcification are more likely to respond to chemotherapy. From a pathological standpoint, IDC-NOS type, negative AR status and higher Ki-67 scores may be associated with chemotherapy sensitivity.}, } @article {pmid28942323, year = {2018}, author = {Nawroth, PP and Bendszus, M and Pham, M and Jende, J and Heiland, S and Ries, S and Schumann, C and Schmelz, M and Schuh-Hofer, S and Treede, RD and Kuner, R and Oikonomou, D and Groener, JB and Kopf, S}, title = {The Quest for more Research on Painful Diabetic Neuropathy.}, journal = {Neuroscience}, volume = {387}, number = {}, pages = {28-37}, doi = {10.1016/j.neuroscience.2017.09.023}, pmid = {28942323}, issn = {1873-7544}, mesh = {Animals ; *Biomedical Research ; Diabetic Neuropathies/*complications/diagnosis/drug therapy ; Disease Progression ; Humans ; Pain/*complications ; }, abstract = {A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.}, } @article {pmid28939238, year = {2017}, author = {Landolfi, A and Troisi, J and Savanelli, MC and Vitale, C and Barone, P and Amboni, M}, title = {Bisphenol A glucuronidation in patients with Parkinson's disease.}, journal = {Neurotoxicology}, volume = {63}, number = {}, pages = {90-96}, doi = {10.1016/j.neuro.2017.09.008}, pmid = {28939238}, issn = {1872-9711}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antiparkinson Agents/therapeutic use ; Benzhydryl Compounds/*blood ; Female ; Glucuronides/*blood ; Humans ; Male ; Middle Aged ; Parkinson Disease/*blood/drug therapy ; Phenols/*blood ; Retrospective Studies ; }, abstract = {BACKGROUND: Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine.

OBJECTIVES: In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls.

METHODS: An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry.

RESULTS: Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (p<0.05). Moreover, no difference in Bisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose.

CONCLUSION: BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity.}, } @article {pmid28938546, year = {2017}, author = {Jin, R and Shen, J and Zhang, T and Liu, Q and Liao, C and Ma, H and Li, S and Yu, Z}, title = {The highly expressed COL4A1 genes contributes to the proliferation and migration of the invasive ductal carcinomas.}, journal = {Oncotarget}, volume = {8}, number = {35}, pages = {58172-58183}, pmid = {28938546}, issn = {1949-2553}, abstract = {BACKGROUND: Invasive ductal carcinoma is a kind of very typical breast cancer. The goal of our research was to figure out the molecular mechanism of Invasive ductal carcinoma and to find out its potential therapy targets.

RESULTS: The total amount of 478 differentially expressed genes in Invasive ductal carcinoma which compared with normal breast epithelial cells were recognized. Functional enrichment analysis proved the most part of differentially expressed genes had connection with ECM-receptor interaction. The two genes lists were contrasted in PPI network, and miRNA regulation networks, The most two crucial genes were identified in our study, which may be helpful to improve Invasive ductal carcinoma treatment. Additionally, experimental results shows that the COL4A1 gene, one of identified genes, played important roles in both of proliferation and colony formation in Invasive ductal carcinoma.

CONCLUSIONS: Invasive ductal carcinoma could have connection with ECM-receptor mutations. These 9 vital genes could be an important part in the progression of Invasive ductal carcinoma and be offered as therapy targets and prognosis indicator. and the experimental results showed that one of the most crucial genes, COL4A1, was the key gene that influence the proliferation and colony formation of the Invasive ductal carcinoma cell.}, } @article {pmid28938000, year = {2017}, author = {Suchanski, J and Tejchman, A and Zacharski, M and Piotrowska, A and Grzegrzolka, J and Chodaczek, G and Nowinska, K and Rys, J and Dziegiel, P and Kieda, C and Ugorski, M}, title = {Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0184970}, pmid = {28938000}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line ; Cell Movement/*physiology ; Coculture Techniques ; Disease Progression ; Endothelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness/physiopathology ; RNA, Messenger/metabolism ; }, abstract = {In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such podoplanin-mediated effects can affect tube formation by endothelial cells and participate in their pathological properties in the tumor context. Our experimental data were supported by clinical studies. First, when IDC and DCIS were analyzed by immunohistochemistry according to the presence of podoplanin-expressing cells, the numbers of cancer-associated fibroblasts with high expression of this glycoprotein were significantly higher in IDC than in DCIS cases. Second, using immunofluorescence, the co-localization of PDPN-positive CAFs with blood vessels stained with antibody directed against CD34 was observed in tumor stroma of IDC samples.}, } @article {pmid28936231, year = {2016}, author = {Fisher, PA and Frenkel, TI and Noll, LK and Berry, M and Yockelson, M}, title = {Promoting Healthy Child Development via a Two-Generation Translational Neuroscience Framework: The Filming Interactions to Nurture Development Video Coaching Program.}, journal = {Child development perspectives}, volume = {10}, number = {4}, pages = {251-256}, pmid = {28936231}, issn = {1750-8592}, support = {P50 DA035763/DA/NIDA NIH HHS/United States ; R01 HD075716/HD/NICHD NIH HHS/United States ; }, abstract = {In this article, we focus on applying methods of translational neuroscience to two-generation, family-based interventions. In recent years, a small but growing body of evidence has documented the reversibility of some of the neurobiological effects of early adversity in the context of environmental early interventions. Some of these interventions are now being implemented at scale, which may help reduce disparities in the face of early life stress. Further progress may occur by extending these efforts to two-generation models that target caregivers' capabilities to improve children's outcomes. In this article, we describe the content and processes of the Filming Interactions to Nurture Development (FIND) video coaching intervention. We also discuss the two-generation, translational neuroscience framework on which FIND is based, and how similar approaches can be developed and scaled to mitigate the effects of adversity.}, } @article {pmid28935854, year = {2017}, author = {Lancellotta, V and Iacco, M and Perrucci, E and Zucchetti, C and Dipilato, AC and Falcinelli, L and Palumbo, I and Aristei, C}, title = {Comparison of Helical Tomotherapy and Direct Tomotherapy in Bilateral Whole Breast Irradiation in a Case of Bilateral Synchronous Grade 1 and Stage 1 Breast Cancer.}, journal = {The American journal of case reports}, volume = {18}, number = {}, pages = {1020-1023}, pmid = {28935854}, issn = {1941-5923}, mesh = {Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/therapy ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Adjuvant/*methods ; *Radiotherapy, Intensity-Modulated ; }, abstract = {BACKGROUND Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. CASE REPORT A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative). Lymph node biopsy and histology, chest X-ray, abdominal ultrasound scan, and bone scintigraphy were negative for metastases (both tumors were Stage 1). Adjuvant therapy with commenced with anastrozole, but no chemotherapy was given. Clinical target volumes (CTVs) were contoured on computed tomography (CT) images. For planning target volumes (PTVs), CTVs were expanded by 1 cm in all directions, except for the medial 5 mm. Since dose constraints to organs at risk (OARs) were beyond established limits, CTVs were expanded by 5 mm. For PTVs, OAR doses and homogeneity indices for helical tomotherapy and direct tomotherapy were compared. Helical tomotherapy provided better target volume coverage and OAR sparing than direct tomotherapy. CONCLUSIONS In a case of bilateral synchronous Stage 1 and Grade 1 breast cancer, helical tomotherapy appeared more suitable than direct tomotherapy.}, } @article {pmid28935545, year = {2018}, author = {Stires, H and Heckler, MM and Fu, X and Li, Z and Grasso, CS and Quist, MJ and Lewis, JA and Klimach, U and Zwart, A and Mahajan, A and Győrffy, B and Cavalli, LR and Riggins, RB}, title = {Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.}, journal = {Molecular and cellular endocrinology}, volume = {471}, number = {}, pages = {105-117}, pmid = {28935545}, issn = {1872-8057}, support = {U54 CA149147/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*drug effects/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/drug effects ; Glutamic Acid/metabolism ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Mutation/genetics ; Protein Kinase Inhibitors/pharmacology ; Receptors, Estrogen/metabolism ; Receptors, Metabotropic Glutamate/*metabolism ; *Signal Transduction/drug effects ; Tamoxifen/*pharmacology ; Transcriptome/drug effects/genetics ; Exome Sequencing ; }, abstract = {Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.}, } @article {pmid28934992, year = {2017}, author = {Plonczak, AM and DiMarco, AN and Dina, R and Gujral, DM and Palazzo, FF}, title = {Breast cancer metastases to the thyroid gland - an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {269}, pmid = {28934992}, issn = {1752-1947}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma/diagnosis/*secondary/surgery ; Carcinoma, Papillary/diagnosis ; Chemotherapy, Adjuvant ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Mastectomy ; Middle Aged ; Neck Dissection ; Radiotherapy, Adjuvant ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnosis/*secondary/surgery ; Thyroidectomy ; }, abstract = {BACKGROUND: Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature.

CASE PRESENTATION: A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy.

CONCLUSIONS: A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally indicates poor prognosis, obviating the need of surgery in an already compromised patient. An empirical thyroidectomy should be considered in select patients for local disease control.}, } @article {pmid28932733, year = {2017}, author = {Moon, EJ and Kim, SB and Chung, JY and Song, JY and Yi, JW}, title = {Pectoral nerve block (Pecs block) with sedation for breast conserving surgery without general anesthesia.}, journal = {Annals of surgical treatment and research}, volume = {93}, number = {3}, pages = {166-169}, pmid = {28932733}, issn = {2288-6575}, abstract = {Most regional anesthesia in breast surgeries is performed as postoperative pain management under general anesthesia, and not as the primary anesthesia. Regional anesthesia has very few cardiovascular or pulmonary side-effects, as compared with general anesthesia. Pectoral nerve block is a relatively new technique, with fewer complications than other regional anesthesia. We performed Pecs I and Pec II block simultaneously as primary anesthesia under moderate sedation with dexmedetomidine for breast conserving surgery in a 49-year-old female patient with invasive ductal carcinoma. Block was uneventful and showed no complications. Thus, Pecs block with sedation could be an alternative to general anesthesia for breast surgeries.}, } @article {pmid28929041, year = {2017}, author = {Dosani, M and Schrader, KA and Nichol, A and Sun, S and Shenkier, T and Lohn, Z and Aubertin, G and Tyldesley, S}, title = {Severe Late Toxicity After Adjuvant Breast Radiotherapy in a Patient with a Germline Ataxia Telangiectasia Mutated Gene: Future Treatment Decisions.}, journal = {Cureus}, volume = {9}, number = {7}, pages = {e1458}, pmid = {28929041}, issn = {2168-8184}, abstract = {Ataxia telangiectasia mutated (ATM) gene mutations may confer increased sensitivity to ionizing radiation and increased risk of late toxicity for cancer patients. We present the case of a 55-year-old female treated with adjuvant breast and regional nodal radiation following lumpectomy and axillary lymph node dissection for stage II invasive ductal carcinoma of the breast. She developed severe telangiectasia, fibrosis, induration, chest wall pain (with evidence of rib fractures on imaging), and painful limitation in her range of motion at the shoulder. She was subsequently found to have a likely pathogenic germline ATM gene mutation. At relapse, she elected to pursue systemic therapy alone for intracranial metastases.}, } @article {pmid28928811, year = {2017}, author = {Tan, H and Zhang, J and Fu, D and Zhu, Y}, title = {Loss of fibulin-2 expression is involved in the inhibition of breast cancer invasion and forms a new barrier in addition to the basement membrane.}, journal = {Oncology letters}, volume = {14}, number = {3}, pages = {2663-2668}, pmid = {28928811}, issn = {1792-1074}, abstract = {Previous studies have demonstrated that fibulin-2 may facilitate cancer cell invasion and metastasis during tumor progression. In the present study, immunohistochemical analyses of fibulin-2 and collagen IV expression in 35 patients with breast cancer were performed to define their localization and association with breast cancer tissue. Fibulin-2 was revealed to be expressed in all tissues surrounding the breast ducts and blood vessels in normal breast tissue, while its expression was not integrated in invasive ductal carcinoma or terminal duct-lobular unit. In malignant breast tissue, collagen IV was integrated around the duct, while fibulin-2 was expressed around collagen IV and was incomplete. These results demonstrated that fibulin-2 was associated with breast cancer invasion. Fibulin-2 expression decreased prior to basement membrane (BM) degradation, indicating that fibulin-2 forms an additional barrier around the BM. Therefore, it was proposed that fibulin-2 composes the general BM, which differs from the traditional BM. These results provide insight into extracellular matrix components and the involvement of fibulin-2 in tumor invasion and metastasis. Fibulin-2 was involved in the process of breast cancer development. It performed an important role in prevention of cancer cell penetration and metastasis.}, } @article {pmid28927045, year = {2017}, author = {Qiu, X and Mei, J and Yin, J and Wang, H and Wang, J and Xie, M}, title = {Correlation analysis between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer.}, journal = {Oncology letters}, volume = {14}, number = {3}, pages = {2912-2918}, pmid = {28927045}, issn = {1792-1074}, abstract = {This study investigated expression of proliferating cell nuclear antigen (PCNA), proliferation-associated nuclear antigen (Ki-67) and cyclooxygenase-2 (COX-2) in tissues of breast invasive ductal carcinoma, and analyzed the correlations between these indexes and X-ray features in mammography. A total of 90 patients who were admitted to Huangshi Central Hospital and diagnosed as breast invasive ductal carcinoma from January 2014 to January 2016 were selected. The expression of PCNA, Ki-67 and COX-2 in cancer tissues and cancer-adjacent normal tissues of patients were detected by immunohistochemical staining, and X-ray features in mammography of patients were observed. By using Spearman correlation analysis, the correlations between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer were investigated. As a result, the positive expression rates of PCNA, Ki-67 and COX-2 in cancer tissues of the patient groups were respectively 42.2, 45.6 and 51.1%, which were significantly higher than those in cancer-adjacent normal tissues of the control group (p<0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group was associated with clinical staging and lymphatic metastasis (p<0.05), but had no correlation with age and tumor size (p>0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group had no correlation with the existence of lumps and localized density-increased shadows (p>0.05), but were associated with manifestations of architectural distortion, calcification as well as skin and nipple depression (p<0.05). Spearman correlation analysis revealed that there was a significantly positive correlation between the expression of PCNA and COX-2 in cancer tissues of the patient group (r=0.676, p<0.05); there was a significantly positive correlation between the expression of Ki-67 and COX-2 (r=0.724, p<0.05); PCNA expression had no obvious correlation with the expression of Ki-67 (p>0.05). In conclusion, PCNA, Ki-67 and COX-2 expression is of great significance in the occurrence, invasion and metastasis of breast invasive ductal carcinoma. There is a strong correlation between PCNA, Ki-67 and COX-2 expression levels and X-ray features in mammography in breast invasive ductal carcinoma. The application of X-ray features in mammography can evaluate the expression levels of PCNA, Ki-67 and COX-2 in tissues of breast invasive ductal carcinoma, thereby prospectively predicting biological behavior of these cancer cells and patient prognosis.}, } @article {pmid28926869, year = {2018}, author = {Kumar, V and Sulaj, A and Fleming, T and Nawroth, PP}, title = {[Not Available].}, journal = {Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {126}, number = {3}, pages = {141-147}, doi = {10.1055/s-0043-110478}, pmid = {28926869}, issn = {1439-3646}, mesh = {Animals ; Mice ; Receptor for Advanced Glycation End Products/*chemistry/*isolation & purification/*metabolism ; }, abstract = {The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor which belongs to the pattern recognition receptor family and can bind to various ligands such as advanced glycation end-products (AGEs), members of the S100 protein family, glycosaminoglycans, amyloid β peptides, high-mobility group box-1 (HMGB1) and nucleic acids through its extracellular domain. The RAGE-ligand interaction leads to the activation of MAP kinase and NF-kB signaling pathways. Further ligand-induced up-regulation of RAGE is involved in various patho-physiological situations including late diabetic complications, Alzheimer disease and several other neurodegenerative diseases. A secreted soluble isoform of RAGE (sRAGE), corresponding to the extracellular domain only, has the ability to block RAGE-associated cellular activation and signaling. Further application of recombinant sRAGE has been shown to block RAGE-mediated pathophysiological conditions in various models of cancer or multiple sclerosis. These finding demonstrates sRAGE as a therapeutic tool to block RAGE-associated inflammatory signaling. In this manuscript, we describe a two-step simple, novel and convenient method for expressing and purifying scalable quantities of biologically active murine form of sRAGE by using E.coli as an expression host. The method we propose has several advantages over the current available methods particularly in terms of yield and quality of preparation. The sRAGE produced by this expression system retains all the secondary structural properties as analyzed by the ligand binding affinities. The produced protein also retains all the DNA-RAGE binding functional properties and thus can be a valuable tool for studying dynamics of this novel RAGE ligand. Moreover this method can be utilized by researchers to generate biologically active endotoxin-free sRAGE for in vivo applications to study and treat RAGE-associated pathologies.}, } @article {pmid28924531, year = {2017}, author = {İyikesici, MS and Slocum, AK and Slocum, A and Berkarda, FB and Kalamian, M and Seyfried, TN}, title = {Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer.}, journal = {Cureus}, volume = {9}, number = {7}, pages = {e1445}, pmid = {28924531}, issn = {2168-8184}, abstract = {Triple-negative breast cancer (TNBC) is more aggressive and metastatic than other breast cancer types. Cytotoxic chemotherapy is presently the predominant systemic therapy for TNBC patients. This case report highlights the influence of metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT) in an overweight 29-year-old woman with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast. The patient presented with an observable mass in her left breast detected during a physical examination in December 2015. Magnetic resonance imaging revealed a Breast Imaging Reporting and Data System Category 5 tumor and multiple lymphadenomegaly in the left axilla. A Tru-Cut biopsy led to the diagnosis of a triple-negative nuclear grade 2 invasive ductal carcinoma. The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey in October 2016, and a whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed a 77 mm x 55 mm primary tumor in her left breast, multiple left pectoral and axillary lymph nodes, multiple widespread liver masses, and an upper left nodular abdominal lesion. The patient received a treatment protocol consisting of MSCT, KD, HT, and HBOT. A follow-up whole body 18F-FDG PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake. The patient continued to receive this treatment protocol and in April 2017 underwent a mastectomy, which revealed a complete pathological response consistent with the response indicated by her PET-CT imaging. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC.}, } @article {pmid28919182, year = {2017}, author = {Dinerman, BF and Khani, F and Golan, R and Bernstein, AN and Cosiano, MF and Margolis, DJ and Hu, JC}, title = {Population-based study of the incidence and survival for intraductal carcinoma of the prostate.}, journal = {Urologic oncology}, volume = {35}, number = {12}, pages = {673.e9-673.e14}, doi = {10.1016/j.urolonc.2017.08.015}, pmid = {28919182}, issn = {1873-2496}, mesh = {Aged ; Carcinoma, Ductal/pathology/*surgery ; Humans ; Incidence ; Lymphatic Metastasis ; Male ; Middle Aged ; Population Surveillance/*methods ; Prognosis ; Proportional Hazards Models ; Prostatectomy/*methods ; Prostatic Neoplasms/pathology/*surgery ; Retrospective Studies ; SEER Program/statistics & numerical data ; Survival Analysis ; United States/epidemiology ; }, abstract = {PURPOSE: The degree to which intraductal carcinoma of the prostate (IDC-P) affects clinical course remains poorly understood owing to small sample sizes from single-center studies. We sought to determine prognostic factors and outcomes associated with IDC-P in radical prostatectomy (RP) specimens.

MATERIALS AND METHODS: This is a retrospective study of RP during 2004 to 2013 using Surveillance, Epidemiology, and End Results to compare IDC-P with non-IDC-P. The effect of IDC-P on overall and disease-specific survival was assessed using Cox regression with a median follow-up of 4.8 years (interquartile range [IQR]: 2.6-7.0y; P = 0.01). Median prostate-specific antigen at diagnosis in IDC-P vs. non-IDC-P was similar (P = 0.23) at 6.2 (IQR: 4.6-13.0) vs. 6.1ng/ml (IQR: 4.6-9.8).

RESULTS: We identified 159,777 RP from 2004 to 2013, and 242 (0.002%) had IDC-P pathologic features. IDC-P was associated with a greater likelihood of extraprostatic stage, pT3/T4, 45.9% vs. 21.6% (P<0.001), higher grade, GS≥ 7, 79.3% vs. 62.7% (P<0.001), lymph node metastases, 5.8% vs. 2.4% (P<0.001), and positive surgical margins, 25.6% vs. 19.5% (P = 0.02). IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality relative to non-IDC-P (hazard ratio = 3.0, 95% CI: 1.5-5.7; P<0.01). Limitations include retrospective design and potential underreporting of IDC-P that leads to underestimation of the true effect size.

CONCLUSIONS: The significance of IDC-P features has been recently recognized by the World Health Organization and it is associated with high-grade, extraprostatic features, and worse prostate cancer-specific mortality. Understanding its prognostic significance better guides adjuvant therapies and clinical trials.}, } @article {pmid28913115, year = {2016}, author = {Çift, T and Aslan, B and Bulut, B and İlvan, Ş}, title = {Unusual uterine metastasis of invasive ductal carcinoma: A case report.}, journal = {Turkish journal of obstetrics and gynecology}, volume = {13}, number = {3}, pages = {164-166}, pmid = {28913115}, issn = {2149-9322}, abstract = {Metastatic carcinoma of the uterus usually originates from other genital sites. Extragenital metastases such as breast are rare. A woman aged 34 years with a history of breast cancer was referred to the gynecology outpatient clinic for routine follow-up. Diagnostic tests and gynecologic examination revealed a uterine mass, which was removed with laparotomy. The pathologic investigation revealed metastasis of invasive lobular breast cancer. Chemotherapy was given and the patient has been under follow-up for 3 years with normal imaging on comput-erized tomographic examination and positron-emission tomography-computerized tomographic. It should be kept in mind that patients with breast cancer who have received tamoxifen may develop primary endometrial cancers, and may also demonstrate uterine metastases. With successful treatment these patients can obtain dis-ease-free survival.}, } @article {pmid28906374, year = {2017}, author = {Golmohammadi, R and Namazi, MJ and Going, JJ and Derakhshan, MH}, title = {A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.}, journal = {Medicine}, volume = {96}, number = {37}, pages = {e7933}, pmid = {28906374}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aurora Kinase A/*genetics ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Case-Control Studies ; Codon ; Female ; Humans ; Iran ; Middle Aged ; Neoplasm Invasiveness ; *Polymorphism, Single Nucleotide ; Prognosis ; Survival Rate ; Young Adult ; }, abstract = {Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.}, } @article {pmid28903426, year = {2017}, author = {Zhao, J and Shen, P and Sun, G and Chen, N and Liu, J and Tang, X and Huang, R and Cai, D and Gong, J and Zhang, X and Chen, Z and Li, X and Wei, Q and Zhang, P and Liu, Z and Liu, J and Zeng, H}, title = {The prognostic implication of intraductal carcinoma of the prostate in metastatic castration-resistant prostate cancer and its potential predictive value in those treated with docetaxel or abiraterone as first-line therapy.}, journal = {Oncotarget}, volume = {8}, number = {33}, pages = {55374-55383}, pmid = {28903426}, issn = {1949-2553}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed using Kaplan-Meier curves, Log-rank test, Cox regression models and Harrell's C-index. The incidence of IDC-P in mCRPC reached 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with a 20-month decrease in OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in abiraterone-treated and docetaxel-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in abiraterone-treated group vs. docetaxel-treated group (52.4% vs. 21.7%; p = 0.035). Also, PSA-PFS and OS were much longer in the IDC-P(+) abiraterone-treated group vs. the docetaxel-treated group (PSA-PFS: 13.5 vs.6.0 months, p = 0.012; OS: not reach vs.14.7 months, p = 0.128). Overall, IDC-P in mCRPC from re-biopsy was an independent prognosticator for clinical outcome. Abiraterone was observed having a better therapeutic efficacy than docetaxel as the first-line therapy in IDC-P(+) mCRPC patients. Thus, we suggest IDC-P should be considered as a novel predictive marker helping physicians making treatment decisions for mCRPC.}, } @article {pmid28902360, year = {2017}, author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Matkowski, R and Wojnar, A and Rys, J and Ugorski, M and Dziegiel, P}, title = {Expression of periostin in breast cancer cells.}, journal = {International journal of oncology}, volume = {51}, number = {4}, pages = {1300-1310}, doi = {10.3892/ijo.2017.4109}, pmid = {28902360}, issn = {1791-2423}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Adhesion Molecules/*genetics/*metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Tumor Burden ; Up-Regulation ; }, abstract = {Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.}, } @article {pmid28901319, year = {2017}, author = {Tan, R and Wang, L and Song, J and Li, J and He, T}, title = {Expression and significance of Twist, estrogen receptor, and E-cadherin in human breast cancer cells and tissues.}, journal = {Journal of cancer research and therapeutics}, volume = {13}, number = {4}, pages = {707-714}, doi = {10.4103/jcrt.JCRT_1396_16}, pmid = {28901319}, issn = {1998-4138}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis ; Nuclear Proteins/*genetics ; Receptors, Estrogen/*genetics ; Twist-Related Protein 1/*genetics ; }, abstract = {OBJECTIVES: Breast cancer is one of the most common malignancies in women, and the tumor cells' invasion and metastasis is the main cause of death. Recent reports showed that Twist, a transcription factor, plays multiple roles in breast cancer initiation, progress, and metastasis. However, the underlying mechanisms of Twist in tumor invasion and metastasis of breast cancer still remain unclear. Here, we examined the correlation between Twist, E-cadherin, and estrogen receptor (ER) in promoting invasion and metastasis in breast cancer cells and tissues.

MATERIALS AND METHODS: The mRNA and protein expression of Twist, E-cadherin, and ER in breast cancer cell lines (MCF-7, MDA-MB-435, MDA-MB-231, and ZR-75-30) and human invasive ductal carcinoma (IDC) tissues from 32 patients were detected by reverse transcription-polymerase chain reaction and immunohistochemistry (IHC), respectively.

RESULTS: Expression of Twist in cells with high ability of invasion and metastasis was higher than that in MCF-7 cell line which has low ability of invasion and metastasis, while the expression of ER and E-cadherin was much more higher in MCF-7 cell line than in other cells. IHC showed that the expression rate of Twist in IDC tissues and adjacent tissues was 84.38% and 31.25% and the positive expression of E-cadherin and ER was 21.88% and 40.63% in IDC tissues and 81.25% and 84.38% in adjacent tissues, respectively. Interestingly, overexpression of Twist promoted cellular invasion and metastasis and decreased the expression of E-cadherin, ER, AKT, and p-AKT in HEK-293 cells.

CONCLUSIONS: Taken together, these findings demonstrated that Twist was upregulated in high invasion and metastasis cell lines as well as IDC tissues companioned with downregulated expression of E-cadherin and ER, which provides important clues for the deeper study of breast cancer.}, } @article {pmid28900633, year = {2017}, author = {Stemmer, SM and Steiner, M and Rizel, S and Soussan-Gutman, L and Ben-Baruch, N and Bareket-Samish, A and Geffen, DB and Nisenbaum, B and Isaacs, K and Fried, G and Rosengarten, O and Uziely, B and Svedman, C and McCullough, D and Maddala, T and Klang, SH and Zidan, J and Ryvo, L and Kaufman, B and Evron, E and Karminsky, N and Goldberg, H and Shak, S and Liebermann, N}, title = {Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.}, journal = {NPJ breast cancer}, volume = {3}, number = {}, pages = {33}, pmid = {28900633}, issn = {2374-4677}, abstract = {The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.}, } @article {pmid28900632, year = {2017}, author = {Stemmer, SM and Steiner, M and Rizel, S and Geffen, DB and Nisenbaum, B and Peretz, T and Soussan-Gutman, L and Bareket-Samish, A and Isaacs, K and Rosengarten, O and Fried, G and McCullough, D and Svedman, C and Shak, S and Liebermann, N and Ben-Baruch, N}, title = {Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.}, journal = {NPJ breast cancer}, volume = {3}, number = {}, pages = {32}, pmid = {28900632}, issn = {2374-4677}, abstract = {The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.}, } @article {pmid28899737, year = {2017}, author = {Cao, L and Sun, PL and Yao, M and Jia, M and Gao, H}, title = {Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues.}, journal = {Human pathology}, volume = {68}, number = {}, pages = {166-174}, doi = {10.1016/j.humpath.2017.08.032}, pmid = {28899737}, issn = {1532-8392}, mesh = {Adaptor Proteins, Signal Transducing/*analysis ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma/*chemistry/mortality/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Phosphoproteins/*analysis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Transcription Factors ; YAP-Signaling Proteins ; }, abstract = {The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor, progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan-Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival in patients with luminal A breast cancer and with favorable DFS association among patients with invasive ductal carcinoma, luminal B (HER2-), and luminal B (HER2+) breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and overall survival, respectively, among patients with breast cancer, whereas tumor-node-metastasis stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.}, } @article {pmid28894989, year = {2017}, author = {Khalil, AA and Ilina, O and Gritsenko, PG and Bult, P and Span, PN and Friedl, P}, title = {Collective invasion in ductal and lobular breast cancer associates with distant metastasis.}, journal = {Clinical & experimental metastasis}, volume = {34}, number = {6-7}, pages = {421-429}, pmid = {28894989}, issn = {1573-7276}, support = {Fellowship//Graduate School for Life Sciences, University of Würzburg/International ; 918.11.626-Vici//NWO/International ; 617430-DEEPINSIGHT//The European Research Council/International ; }, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Lobular/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness/*pathology ; }, abstract = {Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and "Indian files" in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell-cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination.}, } @article {pmid28894845, year = {2017}, author = {Lou, J and Zhou, Y and Huang, J and Qian, X}, title = {Relationship Between PD-L1 Expression and Clinical Characteristics in Patients with Breast Invasive Ductal Carcinoma.}, journal = {Open medicine (Warsaw, Poland)}, volume = {12}, number = {}, pages = {288-292}, pmid = {28894845}, issn = {2391-5463}, abstract = {OBJECTIVE: To evaluate the expression of PD-L1 (programmed death 1 ligand 1, PD-L1) and its clinical significance in breast invasive ductal carcinoma.

METHODS: Tumor samples were collected from 64 cases of breast invasive ductal carcinoma patients, and tumor adjacent normal breast tissue were obtained as normal control. The expression of PD-L1 were examined by immunohistochemical staining and real time PCR assay, its correlations with patients' clinical pathological characteristics were analyzed.

RESULTS: PD-L1 was found to be over-expressed in 24 of 64 (37.5%) breast invasive ductal carcinoma samples, while in 1 of 22 (4.5%) tumor adjacent normal breast tissue which indicated PD-L1 was higher expressed in breast invasive ductal carcinoma samples than the tumor adjacent normal breast tissue (P < 0.05). PD-L1 positive expression was associated with clinical pathological characteristics of TNM stage and pathology grading (P < 0.05). However, PD-L1 positive expression was not correlated with age (P > 0.05), menstruation status (P >0.05), family history of breast cancer (P > 0.05), tumor diameter (P > 0.05), lymph node metastasis (P > 0.05) and tumor location (P > 0.05).

CONCLUSION: PD-L1 may play an important role in invasive ductal carcinoma, which could be a potential indicator for advanced clinical stage and poor prognosis.}, } @article {pmid28892901, year = {2017}, author = {Shubham, S and Maan, P and Singh, M and Bhardwaj, M}, title = {Invasive Ductal Carcinoma Breast: How Neoadjuvant Chemotherapy Affects the Status of Estrogen Receptor, Progesterone Receptor and HER2/Neu-A Tertiary Care Centre Study.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {11}, number = {7}, pages = {EC06-EC08}, pmid = {28892901}, issn = {2249-782X}, abstract = {INTRODUCTION: Determination of Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2/neu in primary Invasive Ductal Carcinoma (IDC) breast is the standard of care parameter for determining treatment options. Whether or not Neoadjuvant Chemotherapy (NAC) affects the receptor status is still an unanswered question.

AIM: To compare immunohistochemical (IHC) profiles of ER, PR and HER2/neu in primary IDC breast before and after NAC to assess the subsequent effects on receptor status.

MATERIALS AND METHODS: Thirty two patients diagnosed with primary IDC breast who had a previous breast core biopsy with complete IHC profile followed by NAC and Modified Radical Mastectomy (MRM) were included. For each case demographic and histologic data was collected, including age, grade, amount of necrosis post NAC and IHC panel for ER, PR and HER2/neu in core biopsies. The same IHC panel was applied on Post NAC MRM specimen. Pre- and post NAC IHC expression was compared.

RESULTS: Patients ranged from 30 years to 75 years in range. ER, PR and HER2/neu status of core biopsies and MRM specimen were compared and overall agreement was noted. Comparison for each receptor was done using McNemar's test and significance was calculated. There was no statistically significant difference in ER and Her2/neu expression between pre- and post-NAC specimens. However, a statistically significant loss of PR expression was noted between the two groups.

CONCLUSION: Accurate determination of ER, PR and Her2/neu status in primary IDC breast is important to guide further treatment. Change in receptor status post NAC may warrant corresponding change in hormonal therapy.}, } @article {pmid28891551, year = {2017}, author = {Olarinoye-Akorede, SA and Silas, BT}, title = {Mondor's disease of the breast in a Nigerian woman previously treated for invasive ductal carcinoma in the contralateral breast: A case report.}, journal = {Nigerian journal of clinical practice}, volume = {20}, number = {8}, pages = {1040-1043}, doi = {10.4103/njcp.njcp_354_16}, pmid = {28891551}, issn = {1119-3077}, mesh = {Breast/diagnostic imaging ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Female ; Humans ; Middle Aged ; Nigeria ; Pain/etiology ; Thrombophlebitis/*complications/*diagnostic imaging ; }, abstract = {Mondor's disease is a self-limiting sclerosing angitis mostly affecting the superficial veins of the breast and chest wall. It is seldom diagnosed, and its etiology and epidemiology are speculative. However, numerous predisposing factors including breast cancer have been postulated. In Nigerian literature, only two cases have been documented to the best of our knowledge. This report is aimed at reminding breast specialists to include it as a diagnostic consideration in patients presenting with a breast lump in the appropriate clinical setting. Its imaging features are also highlighted because it may be incorrectly overlooked as mere ductal dilatation. We present the case of a 60-year-old woman who complained of a painful cordlike lesion in her right breast. Mondor's disease was diagnosed based on the clinical and radiological findings. She had also been previously treated for invasive ductal breast carcinoma in the contralateral breast. Mondor's disease is usually a benign entity, which may resolve spontaneously. On the other hand, it may also be the sole presenting symptom or clue of a breast malignancy; hence, a need for increased awareness.}, } @article {pmid28890183, year = {2018}, author = {Guo, Y and Hu, Y and Qiao, M and Wang, Y and Yu, J and Li, J and Chang, C}, title = {Radiomics Analysis on Ultrasound for Prediction of Biologic Behavior in Breast Invasive Ductal Carcinoma.}, journal = {Clinical breast cancer}, volume = {18}, number = {3}, pages = {e335-e344}, doi = {10.1016/j.clbc.2017.08.002}, pmid = {28890183}, issn = {1938-0666}, mesh = {Adult ; Biopsy ; Breast/diagnostic imaging/pathology/surgery ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/surgery ; Feasibility Studies ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Support Vector Machine ; Ultrasonography, Mammary/*methods ; }, abstract = {INTRODUCTION: In current clinical practice, invasive ductal carcinoma is always screened using medical imaging techniques and diagnosed using immunohistochemistry. Recent studies have illustrated that radiomics approaches provide a comprehensive characterization of entire tumors and can reveal predictive or prognostic associations between the images and medical outcomes. To better reveal the underlying biology, an improved understanding between objective image features and biologic characteristics is urgently required.

PATIENTS AND METHODS: A total of 215 patients with definite histologic results were enrolled in our study. The tumors were automatically segmented using our phase-based active contour model. The high-throughput radiomics features were designed and extracted using a breast imaging reporting and data system and further selected using Student's t test, interfeature coefficients and a lasso regression model. The support vector machine classifier with threefold cross-validation was used to evaluate the relationship.

RESULTS: The radiomics approach demonstrated a strong correlation between receptor status and subtypes (P < .05; area under the curve, 0.760). The appearance of hormone receptor-positive cancer and human epidermal growth factor receptor 2-negative cancer on ultrasound scans differs from that of triple-negative cancer.

CONCLUSION: Our approach could assist clinicians with the accurate prediction of prognosis using ultrasound findings, allowing for early medical management and treatment.}, } @article {pmid28888337, year = {2017}, author = {Bakula, DM and Sharkey, CM and Wolfe-Christensen, C and Mullins, AJ and Meyer, J and Mullins, LL and Wisniewski, AB}, title = {Recommendations for the Establishment of Disorders/Differences of Sex Development Interdisciplinary Care Clinics for Youth.}, journal = {Journal of pediatric nursing}, volume = {37}, number = {}, pages = {79-85}, doi = {10.1016/j.pedn.2017.08.032}, pmid = {28888337}, issn = {1532-8449}, mesh = {Adolescent ; Adolescent Behavior ; Adolescent Health Services/organization & administration ; Ambulatory Care Facilities/*organization & administration ; Delivery of Health Care/organization & administration ; Disorders of Sex Development/*diagnosis/epidemiology/*therapy ; Female ; Humans ; Male ; Patient Care Team/*organization & administration ; Pediatric Nursing/standards ; *Practice Guidelines as Topic ; Program Evaluation ; United States ; }, abstract = {PURPOSE: Provide recommendations for the development of an interdisciplinary care (IDC) clinic for the treatment of youth with disorders/differences of sex development (DSD). DSD consist of a group of complex congenital medical disorders in which the development of chromosomal, gonadal, or anatomical sex is atypical. Youth with DSD require care from multiple specialized healthcare disciplines, including several medical specialties, surgery, nursing, and mental health.

METHOD: Recommendations are based on an interdisciplinary care clinic model that allows for a team of relevant professionals who share knowledge, ideas, and responsibility of care. The framework established in this article is based largely on experiences at an established DSD clinic, as well as observations of multiple clinics across the United States.

RESULTS: Preliminary outcome data on clinic adherence to treatment protocol under an IDC model are provided.

CONCLUSIONS: To meet the diverse healthcare needs of youth with DSD, comprehensive care clinics are recommended; however, few such clinics exist in the United States. Establishing new comprehensive DSD clinics can be challenging due to the highly unique treatment of DSD, but the current paper expands the literature available to guide clinic development in the United States.}, } @article {pmid28885232, year = {2017}, author = {Bosch, DE and Kilgore, MR and Schmidt, RA and Swanson, PE and Rendi, MH and Chang, OH}, title = {Comparison of Proliferation Markers Ki67 and Phosphohistone-H3 (pHH3) in Breast Ductal Carcinoma In Situ.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {25}, number = {8}, pages = {543-547}, doi = {10.1097/PAI.0000000000000555}, pmid = {28885232}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; *Cell Proliferation ; Female ; Histones/*metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Phosphoproteins/*metabolism ; }, abstract = {Proliferative index is a prognostic feature of invasive ductal carcinoma of the breast, and has more recently emerged as a predictor of ductal carcinoma in situ (DCIS) local recurrence and progression when used in combination with other predictive markers. Ki67 is the most commonly used immunohistochemical marker of proliferative index. However, high interobserver and interlaboratory variability has been reported, in part due to differences in staining methodologies, positivity thresholds, and approaches to quantification. Phosphohistone-H3 (pHH3) is a marker of mitotic activity that has emerged as a more reliable indicator of proliferation in other neoplasms. Quantification of proliferative index was compared in 48 cases of DCIS using Ki67 and pHH3 immunohistochemistry. A strong linear relationship between Ki67 and pHH3 quantification was observed (P<0.0001, R=0.75). Interobserver concordance was modestly higher for pHH3 than Ki67 proliferative indices. However, positive pHH3 staining was more dichotomous (either negative or uniformly positive) and specific for mitotic activity, and interpretation of pHH3 proliferative indices was significantly faster than that of Ki67. The strong correlation between pHH3 and Ki67 supports the use of this marker as a measure of proliferative activity in DCIS.}, } @article {pmid28882157, year = {2017}, author = {Stadtmann, MP and Maercker, A and Binder, J and Schnepp, W}, title = {Symptom management in complex post-traumatic stress disorder (ICD-11), view and experience of patients and their relatives: a mixed methods approach (Research Proposal).}, journal = {BMC research notes}, volume = {10}, number = {1}, pages = {461}, pmid = {28882157}, issn = {1756-0500}, mesh = {Adult ; Clinical Protocols ; Family ; Humans ; *International Classification of Diseases ; Patients ; *Research Design ; Stress Disorders, Post-Traumatic/*therapy ; }, abstract = {OBJECTIVE: Using the framework of IDC-11, complex post-traumatic stress disorder will be diagnosed using the core criteria of a post-traumatic stress disorder and the presence of at least one symptom from the following three domains: symptoms of emotional dysregulation, negative self-concept, and problems in interpersonal relationships. In the literature, these symptoms are discussed as a common reason for seeking treatment. The symptoms can influence and impair the quality of life. This article describes a mixed methods study with a sequential exploratory design. The aim is to describe specific patient characteristics, levels of symptom burden and perspectives of adult inpatients and to describe the experiences, views and needs of patients' relatives. The study will also investigate facilitators of and barriers to symptom management. The research will be conducted in four phases. The first phase will assess patients' symptom burdens. The second phase will use semi-structured interviews to explore attitudes to symptom management and perceptions of patients and their relatives. The third phase will statistically explore hypotheses generated after the qualitative interviews. The fourth phase will mix the quantitative and qualitative results and interpret critically.

RESULTS: The present study will add new results to the growing literature on complex post-traumatic stress disorder. These results could serve as the basis for further research into the development of interventions to improve symptom management. Trial registration Ethical approval has been obtained from the Swiss cantonal ethic commission (Nr. 201500096). This research was also registered to the World Health Organization Clinical Trials Search Portal through the German Clinical Trial Register, Trial DRKS00012268 (21/04/2017).}, } @article {pmid28877837, year = {2017}, author = {Zhang, YQ and Zhao, HY and Sun, Q and Mao, F and Zhou, YD and Zhou, JM}, title = {Clinical Diagnosis and Treatment of Male Breast Cancer:Analysis of 24 Cases.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {39}, number = {4}, pages = {568-572}, doi = {10.3881/j.issn.1000-503X.2017.04.017}, pmid = {28877837}, issn = {1000-503X}, mesh = {Breast Neoplasms, Male/*diagnosis/*therapy ; Humans ; Male ; Mastectomy ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {Objective To summarize our experiences in the clinical diagnosis and treatment of male breast cancer(MBC).Methods The clinical date of 24 MBC patients treated in our hospital from January 2006 to December 2012 were retrospective analyzed.Results The average age of these 24 patients was(55.7±2.1) years.All the patients received surgical treatment,and the surgical procedures were simple excision of breast lesion in 6 patients,breast resection alone in 5 patients,and modified radical mastectomy in 13 patients(bilateral in 1 case).The pathological diagnoses included invasive ductal carcinoma in 18 cases,papillary carcinoma in 4 cases,mucinous adenocarcinoma in 1 case,and malignant solitary fibrous tumor in 1 case.Twenty patients received chemotherapy,7 received radiotherapy,and 15 received endocrine therapy after operation.The 5-year survival rate was 54.2%.Conclusions The incidence of MBC is low.This malignancy is mainly seen in elderly individuals,with relatively long disease course,poor prognosis,and high risk of metastasis.MBC is mainly treated by surgery,and adjuvant chemotherapy,radiotherapy,and endocrine therapy may be applied,if appropriate,after the operation.}, } @article {pmid28872750, year = {2017}, author = {Yuminaga, Y and Kam, J and Louie-Johnsun, M}, title = {Multi-centre, prospective evaluation of the Seldinger technique for difficult male urethral catheter insertions by non-urology trained doctors.}, journal = {BJU international}, volume = {120 Suppl 3}, number = {}, pages = {21-27}, doi = {10.1111/bju.13928}, pmid = {28872750}, issn = {1464-410X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Education, Medical, Continuing/*methods ; Female ; Humans ; Internet ; Male ; Middle Aged ; Physicians/statistics & numerical data ; Prospective Studies ; Urinary Catheterization/instrumentation/*methods ; *Urinary Catheters ; Urology/*education ; Video Recording ; }, abstract = {OBJECTIVE: To evaluate the safety and effectiveness of the Seldinger technique by non-urology trained (NUT) doctors for difficult male indwelling urinary catheter (IDC) insertions.

PATIENTS AND METHODS: In all, 115 patients and 57 participating NUT doctors were recruited by the urologist or urology registrar, when contacted in regards to failed IDC insertion. The successful passage of an IDC by the NUT doctors using the Seldinger technique with a straight, hydrophilic guidewire was assessed in our prospective, multicentre evaluation. Instruction of this technique was via bedside teaching by the urology registrar or via video media.

RESULTS: The 115 patients, involving 57 NUT doctors, were prospectively evaluated across four sites; 93% (107/115) of cases had successful placement of an IDC with the Seldinger technique by a NUT doctor. No complications with the Seldinger technique were recorded. In 80 patients (69.6%), the technique was successfully performed by a NUT doctor without attendance by a urologist or urology registrar, with instruction provided from video media or prior bedside teaching by the urology registrar.

CONCLUSIONS: Our study is the first to validate the safety and effectiveness of the Seldinger technique for difficult male IDC insertion performed by NUT doctors. This technique can be taught via video education and thus has important implications for health services where urological support is not readily available.}, } @article {pmid28871133, year = {2017}, author = {Xiao, Y and Ma, D and Ruan, M and Zhao, S and Liu, XY and Jiang, YZ and Shao, ZM}, title = {Mixed invasive ductal and lobular carcinoma has distinct clinical features and predicts worse prognosis when stratified by estrogen receptor status.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {10380}, pmid = {28871133}, issn = {2045-2322}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Female ; Humans ; Neoplasm Grading ; Prognosis ; Proportional Hazards Models ; Receptors, Estrogen/*metabolism ; Retrospective Studies ; Survival Analysis ; }, abstract = {In order to investigate clinicopathological characteristics and prognosis of mixed invasive ductal and lobular carcinoma (IDC-L), 209,109 primary breast cancer patients diagnosed with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) or IDC-L were included. It was found that IDC-L patients had lower tumor grade and higher hormone receptor positive proportions than IDC patients. Moreover, IDC-L patients were younger and had a similar hormone receptor status compared with ILC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of IDC-L patients was significantly better than IDC patients (P < 0.001) and tended to be better than ILC patients (P = 0.166). However, after adjusting for clinicopathological factors, survival advantage of IDC-L disappeared. Subgroup analysis indicated that IDC-L had higher hazard ratios (HRs) than IDC in grade 1, grade 2, ER-positive and ER-negative subgroups. Survival analysis in ER-positive and ER-negative subgroups showed that IDC-L predicted a worse prognosis than IDC. In conclusion, IDC-L is a distinct histological subtype compared with IDC and ILC. Lower grade and higher ER-positive proportions mainly contribute to its better prognosis. In both ER-positive and ER-negative subgroups, IDC-L predicts worse prognosis than IDC, which suggested the inadequacy of IDC-based therapy and the need of escalated therapy.}, } @article {pmid28870933, year = {2017}, author = {Fujii, T and Yanai, K and Tokuda, S and Nakazawa, Y and Kurozumi, S and Obayashi, S and Yajima, R and Hirakata, T and Kuwano, H}, title = {Clinicopathological Features of Ductal Carcinoma In Situ from [18]F-FDG-PET Findings.}, journal = {Anticancer research}, volume = {37}, number = {9}, pages = {5053-5056}, doi = {10.21873/anticanres.11921}, pmid = {28870933}, issn = {1791-7530}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Positron-Emission Tomography ; Radiopharmaceuticals ; }, abstract = {AIM: The presence of ductal carcinoma in situ (DCIS) can increase the risk of developing an invasive ductal carcinoma (IDC), but it is difficult to predict what will occur if a DCIS is left untreated. We reported the usefulness of [18]F-fluorodeoxyglucose positron emission tomography (FDG-PET) for DCIS, and that the presence of FDG uptake in the tumor could be considered a predictor of invasive potential in patients with DCIS. In this study, we retrospectively evaluated the clinicopathological features of DCIS by using FDG-PET findings, and we evaluated the possibility of using FDG-PET in DCIS cases as a biomarker of which lesions will go on to become invasive.

PATIENTS AND METHODS: We investigated the cases of 185 consecutive patients with primary breast cancer who were diagnosed as having DCIS or IDC and underwent FDG-PET preoperatively.

RESULTS: We divided the cases into two groups on the basis of histology; DCIS vs. IDC (n=171). The DCIS cases were divided into two groups on the basis of FDG uptake in the primary tumor. Fourteen of the 185 patients (7.4%) were revealed to have a DCIS. The analysis revealed that the SUVmax and the number of cases not detected by FDG-PET were significantly different between the DICS and IDC groups. The extent of the primary tumor was not significantly different between the two groups. In six cases (42.9%) of the 14 DCIS cases, no FDG uptake was detected by FDG-PET. The extent of tumor did not significantly differ between the two groups. In addition, all six cases without FDG uptake were of the diffuse-spread type, without mass formation. All eight cases with mass formation had FDG uptake.

CONCLUSION: Our present findings suggest that the FDG-PET uptake reflects tumor burden or tumor density, which should be considered to be associated with the presence of invasion.}, } @article {pmid28869838, year = {2017}, author = {Turczyk, L and Kitowska, K and Mieszkowska, M and Mieczkowski, K and Czaplinska, D and Piasecka, D and Kordek, R and Skladanowski, AC and Potemski, P and Romanska, HM and Sadej, R}, title = {FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells.}, journal = {Neoplasia (New York, N.Y.)}, volume = {19}, number = {10}, pages = {791-804}, pmid = {28869838}, issn = {1476-5586}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Estrogen Receptor alpha/*metabolism ; Female ; Fibroblast Growth Factors/metabolism ; Fibroblasts/drug effects ; Gene Expression ; Gene Knockout Techniques ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Proteolysis ; Receptor, ErbB-2/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism ; Selective Estrogen Receptor Modulators/*pharmacology ; Signal Transduction/*drug effects ; Tamoxifen/*pharmacology ; }, abstract = {Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.}, } @article {pmid28868787, year = {2018}, author = {Kinoshita, M and Matsuda, Y and Arai, T and Soejima, Y and Sawabe, M and Honma, N}, title = {Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {29}, number = {1}, pages = {22-27}, doi = {10.1111/cyt.12461}, pmid = {28868787}, issn = {1365-2303}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Squamous Cell/*pathology ; Cell Differentiation ; Cell Nucleolus/pathology ; Female ; Humans ; Necrosis/pathology ; }, abstract = {OBJECTIVE: Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast.

METHODS: We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background.

RESULTS: SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, P<.001), cannibalism (60% vs 0%, P=.002), and a necrotic background (80% vs 36%, P=.047) were all significantly more frequent in SCC than in AC. When distinguishing SCC from AC, the presence of two or three of these features yielded a high sensitivity (80%) and specificity (100%).

CONCLUSIONS: Cytological features such as a streaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice.}, } @article {pmid28866132, year = {2017}, author = {Riehl, M and Harms, M and Hanefeld, A and Baleeiro, RB and Walden, P and Mäder, K}, title = {Combining R-DOTAP and a particulate antigen delivery platform to trigger dendritic cell activation: Formulation development and in-vitro interaction studies.}, journal = {International journal of pharmaceutics}, volume = {532}, number = {1}, pages = {37-46}, doi = {10.1016/j.ijpharm.2017.08.119}, pmid = {28866132}, issn = {1873-3476}, mesh = {Adjuvants, Immunologic/*administration & dosage/chemistry ; Antigens/administration & dosage/chemistry ; Dendritic Cells/*drug effects ; Drug Compounding ; *Drug Delivery Systems ; Fatty Acids, Monounsaturated/*administration & dosage/chemistry ; Fluorescent Dyes/administration & dosage/chemistry ; Humans ; Lactic Acid/*administration & dosage/chemistry ; Polyglycolic Acid/*administration & dosage/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer ; Quaternary Ammonium Compounds/*administration & dosage/chemistry ; }, abstract = {The utilization of the cationic lipid R-DOTAP as immune cell stimulant (e.g. its stimulating effects on immature dendritic cells) and correspondingly as possible adjuvant for vaccination is well known. Likewise, it is described in literature that solid polymer particles loaded with antigens can be size-tailored in a manner to be suitable for phagocytosis by antigen presenting cells. The effects of DOTAP-microparticle combinations, however, are not well understood. This study aimed therefore to explore the potential of R-DOTAP stabilized microparticles (MP) to act as a carrier platform for antigens e.g. for cancer vaccination. It was investigated whether or not a combination of R-DOTAP and PLGA leads to a boosted adjuvant effect in dendritic cell maturation. For proper comparison, neutral and negatively charged MPs of comparable sizes were developed. Toxicity, uptake, routing and maturation of the MP platform was assessed in-vitro on human immature dendritic cells (iDCs). Interestingly, none of the tested placebo formulations (without antigen) was capable to induce DC maturation when compared to LPS as positive control. This is in contrast to experiments previously reported in literature, where R-DOTAP (e.g. in liposomal form) triggered iDC maturation even without antigen. Possible reasons and further approaches are discussed in the paper.}, } @article {pmid28865741, year = {2017}, author = {Greenhouse, I and Babushkin, F and Finn, T and Shimoni, Z and Aliman, M and Ben-Ami, R and Cohen, R}, title = {Long-term outcomes of inappropriate antibiotic therapy for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a retrospective cohort study.}, journal = {Diagnostic microbiology and infectious disease}, volume = {89}, number = {3}, pages = {222-229}, doi = {10.1016/j.diagmicrobio.2017.07.011}, pmid = {28865741}, issn = {1879-0070}, mesh = {Aged ; Cohort Studies ; Drug Prescriptions/standards ; Drug Resistance, Bacterial ; *Enterobacteriaceae/enzymology ; Enterobacteriaceae Infections/*drug therapy ; Humans ; Retrospective Studies ; Treatment Outcome ; Urinary Tract Infections/drug therapy/*microbiology ; *beta-Lactamases/biosynthesis/metabolism ; }, abstract = {BACKGROUND: To evaluate the short- and long-term outcomes of different antimicrobial treatment options for upper urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

METHODS: We retrospectively analyzed patients with a first episode of febrile UTI and positive urine culture with ESBL-producing E. coli or K. pneumoniae during 2012-2015. We compared outcomes among patients who received: (1) definitive treatment with a carbapenem (CP), (2) a microbiologically appropriate intravenous non-carbapenem agent (NCA), (3) a non-appropriate antimicrobial (NAA), and (4) an intravenous NAA followed by an oral NCA (NAA-PO).

RESULTS: The majority of patients received empirical therapy with NAA (165/178, 93%), and definitive treatment with NCA (n=43), NAA (n=50), and NAA-PO (n=59). The NCA group had significantly higher SIRS score than the NAA-PO group (2.18 versus 1.76, P=0.018), but no differences were found between the NCA and NAA groups (2.18 and 1.92, P=0.15). Clinical cure at discharge from the index hospitalization was high (97-100%) in all 3 groups. The NCA group had longer length of stay as compared with the NAA-PO and NAA groups (8.7days versus 5.39 and 5.24days, P<0.0001) and a lower rate of early (48-72h) improvement (79% versus 96-100%, P=0.0002). Among re-admitted patients, re-admission with ESBL-related bloodstream infection was significantly higher in the NAA group as compared to the NAA-PO and NCA groups (33% versus 4% and 0%, respectively, P=0.02). Death rate within 60days was also higher in the NAA and NCA groups as compared with the NAA-PO group (P=0.048).

CONCLUSIONS: Inappropriate antimicrobial therapy for febrile non-bacteremic UTI with ESBL-producing enterobacteriaceae is associated with favorable short-term outcomes, but also with a long-term risk of relapsed bacteremic UTI. Definitive treatment with appropriate carbapenem-sparing antimicrobial agents effectively prevents late relapses.}, } @article {pmid28863134, year = {2017}, author = {Chen, Z and Yang, J and Li, S and Lv, M and Shen, Y and Wang, B and Li, P and Yi, M and Zhao, X and Zhang, L and Wang, L and Yang, J}, title = {Invasive lobular carcinoma of the breast: A special histological type compared with invasive ductal carcinoma.}, journal = {PloS one}, volume = {12}, number = {9}, pages = {e0182397}, pmid = {28863134}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; SEER Program ; Treatment Outcome ; United States ; }, abstract = {The clinical outcomes and therapeutic strategies for infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not uniform. The primary objectives of this study were to identify the differences in the clinical characteristics and prognoses between ILC and IDC, and identify the high-risk population based on the hormone receptor status and metastasis sites. The Surveillance, Epidemiology, and End Results Program database was searched and patients diagnosed with ILC or IDC from 1990 to 2013 were identified. In total,796,335 patients were analyzed, including 85,048 withILC (10.7%) and 711,287 withIDC (89.3%). The ILC group was correlatedwith older age, larger tumor size, later stage, lower grade, metastasis disease(M1) disease, and greater counts ofpositive lymph nodesandestrogen-receptor-positive (ER)/progesterone receptor-positive (PR) positive nodes. The overall survival showed an early advantage for ILC but a worse outcome after 5 years. Regarding the disease-specific survival, the IDC cohort had advantages over the ILC group, both during the early years and long-term. In hormone status and metastasis site subgroup analyses, the ER+/PR+ subgroup had the best survival, while the ER+/PR- subgroup had the worst outcome, especially the ILC cohort. ILC and IDC had different metastasis patterns. The proportion of bone metastasis was higher in the ILC group (91.52%) than that in the IDC (76.04%), and the ILC group was more likely to have multiple metastasis sites. Survival analyses showed patients with ILC had a higher risk of liver metastasis (disease-specific survival[DSS]; P = 0.046), but had a better overall survival than the bone metastasis group (P<0.0001). We concluded that the long-term prognosis for ILC was poorer than that for IDC, and the ER+/PR- subgroup had the worst outcome. Therefore, the metastasis pattern and prognosis must be seriously evaluated, and a combination of endocrine therapy and chemotherapy should be considered.}, } @article {pmid28862125, year = {2017}, author = {Stroescu, C and Gilca, I and Chirita, D and Poenaru, R and Puşcaşu, A and Pescaru, D and Birceanu, A and Niţipir, C and Copcă, N}, title = {Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {112}, number = {4}, pages = {473-476}, doi = {10.21614/chirurgia.112.4.473}, pmid = {28862125}, issn = {1221-9118}, mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Neoplasm Invasiveness ; Treatment Outcome ; }, abstract = {The usual neoplastic dissease involving suprarenal glands are adrenal metastaes. The majority of suprarenal metastatic disease arise from lung cancer, followed by the stomach and colon cancer, oesophagus, the liver/bile ducts cancer and renal cell carcinoma. Invasive mammary carcinoma usually spreads to the bones, lungs, lymph nodes, liver and the brain. Adrenal gland metastases from invasive no special type carcinoma represents an extremly low rate number of cases. We discuss about a 66 year old patient who presented with a solitary adrenal metastases from triple negative breast invasive carcinoma. The patient underwent total left adrenalectomy in June 2016. No further adjuvants therapies were performed. At the time of writing the patient is in good condition, without any evidence of recurrence. The role of surgical and adjuvant therapy in treating adrenal metastases after breast cancer in survival rate will be determined in future studies.}, } @article {pmid28861874, year = {2017}, author = {Kunts, TA and Mikhaylova, ES and Marinkin, IO and Varaksin, NA and Autenshlyus, AI and Lyakhovich, VV}, title = {Cytokine production by the tumor from patients with breast cancer in different age groups.}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {475}, number = {1}, pages = {172-174}, pmid = {28861874}, issn = {1608-3105}, mesh = {Adult ; Aged ; Aging/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cytokines/*metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Proteins/*metabolism ; }, abstract = {Dependence of cytokine pattern in the tumor supernatant obtained after cultivation of biopsy samples-on the patients' age was evaluated among patients with invasive ductal carcinoma of the breast. An increase in VEGF and IL-6 production in a group of younger patients was observed. An increase only in interferon γ concentration was revealed in the supernatants of the tumor after addition of polyclonal activators to the culture medium. This result indicates likely secretion of interferon γ in younger patients. The relation among the production of angiogenic factors by tumor cells, age of the patients, and presence or absence of lymph node metastases shows that in such studies, patients have to be stratified by age.}, } @article {pmid28861368, year = {2017}, author = {Yamamoto, S and Chishima, T}, title = {Can magnetic resonance imaging obviate the need for biopsy for microcalcifications?.}, journal = {Gland surgery}, volume = {6}, number = {4}, pages = {302-307}, pmid = {28861368}, issn = {2227-684X}, abstract = {BACKGROUND: Although microcalcifications detected with mammography (MG) are usually biopsied, biopsies cannot be performed in all cases. We sought to determine if magnetic resonance imaging (MRI) findings could indicate whether stereotactic vacuum-assisted biopsy (SVAB) is necessary.

METHODS: Patients with mammographically detected Breast Imaging-Reporting and Data System (BI-RADS) 3, 4, and 5 microcalcifications were analyzed from April 2012 to September 2014. All patients underwent MRI. All patients with enhancing lesions in the region of the microcalcifications underwent SVAB. Non-enhancing lesions were followed or biopsied, depending on the patient's preferences. MRI findings were classified as either malignant-suspicious or benign-suspicious ("none" or "nonspecific"), and we evaluated the positive predictive value (PPV) and negative predictive value (NPV) of these classifications for predicting malignancy.

RESULTS: A total of 87 patients underwent both MRI and SVAB. The NPV of MRI was 100% in the group with no enhancement. In BI-RADS category 3, there were 57 benign-suspicious lesions on MRI, of which eight were malignant (NPV of MRI: 85.0%).

CONCLUSIONS: It may be possible to omit SVAB for microcalcifications if there is no enhancement on MRI; however, any kind of enhancement indicates the need for biopsy in cases of BI-RADS 3 calcifications on MG.}, } @article {pmid28860708, year = {2017}, author = {Li, A and Li, Y and Ge, L and Li, P and Li, W}, title = {Onychomadesis associated with chemotherapy: case report and mini literature review.}, journal = {Drug design, development and therapy}, volume = {11}, number = {}, pages = {2373-2376}, pmid = {28860708}, issn = {1177-8881}, mesh = {Aged ; Albumins/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Breast Neoplasms/therapy ; Capecitabine/administration & dosage ; Carcinoma, Ductal, Breast/therapy ; Female ; Follow-Up Studies ; Humans ; Nail Diseases/*chemically induced/pathology/therapy ; Paclitaxel/administration & dosage ; }, abstract = {The side effects of chemotherapy drugs have increased in recent years, and some side effects can lead to onychomadesis. A 72-year-old woman who was diagnosed with an invasive ductal carcinoma of the right breast underwent a modified radical mastectomy in April 2015, followed by chemotherapy with capecitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Subsequently, the patient experienced palmoplantar redness, pain, onycholysis, a transparent serous exudate, and onychomadesis. The chemotherapy was discontinued, and the patient was treated with oral vitamin B6, a polymyxin ointment, and a high-energy red light. The palmoplantar redness and pain were alleviated after 1 month. However, although her fingernails improved, dysesthesia symptoms remained, and all her toenails exhibited defects or deformities at a 24-month follow-up. The symptoms of this disorder should be recognized by dermatologists.}, } @article {pmid28858565, year = {2018}, author = {Bertrand, A and Brunel, S and Habert, MO and Soret, M and Jaffre, S and Capeau, N and Bourseul, L and Dufour-Claude, I and Kas, A and Dormont, D}, title = {A New Fire Hazard for MR Imaging Systems: Blankets-Case Report.}, journal = {Radiology}, volume = {286}, number = {2}, pages = {568-570}, doi = {10.1148/radiol.2017162921}, pmid = {28858565}, issn = {1527-1315}, mesh = {Bedding and Linens/*adverse effects ; Female ; *Fires ; Humans ; Magnetic Resonance Imaging/*adverse effects ; Metals/*administration & dosage ; Middle Aged ; Multimodal Imaging/adverse effects ; Positron-Emission Tomography/*adverse effects ; }, abstract = {In this report, a case of fire in a positron emission tomography (PET)/magnetic resonance (MR) imaging system due to blanket combustion is discussed. Manufacturing companies routinely use copper fibers for blanket fabrication, and these fibers may remain within the blanket hem. By folding a blanket with these copper fibers within an MR imaging system, one can create an electrical current loop with a major risk of local excessive heating, burn injury, and fire. This hazard applies to all MR imaging systems. Hybrid PET/MR imaging systems may be particularly vulnerable to this situation, because blankets are commonly used for fluorodeoxyglucose PET to maintain a normal body temperature and to avoid fluorodeoxyglucose uptake in brown adipose tissue. [©] RSNA, 2017.}, } @article {pmid28856077, year = {2017}, author = {Nieder, C and Mannsåker, B and Haukland, E}, title = {Exceptional Responses to Standard Therapy in a Patient with Metastatic HER2-Positive Breast Cancer.}, journal = {Cureus}, volume = {9}, number = {6}, pages = {e1412}, pmid = {28856077}, issn = {2168-8184}, abstract = {Patients with metastatic breast cancer involving the liver and brain often have short overall survival. Here, we report a case of de novo metastatic breast cancer with multiple liver metastases at initial diagnosis in February 2011 in a 35-year-old Caucasian female patient. The histology was poorly differentiated invasive ductal carcinoma (estrogen and progesterone receptor negative, HER2 positive) and the patient was negative for germline BRCA 1 and 2 mutations. Systemic therapy with trastuzumab and docetaxel was given for six months and then switched to trastuzumab only because of peripheral neuropathy. At that time, the patient was in complete clinical remission. She developed brain metastases in September 2012 and received whole-brain radiotherapy, which resulted in complete remission. While on continued trastuzumab, the primary tumor in the breast recurred in May 2016. A mastectomy was performed and afterwards systemic therapy was intensified (trastuzumab, pertuzumab, paclitaxel). At the last follow-up (March 06, 2017) no further recurrence was detected. This case illustrates that standard HER2-directed treatment might provide long-term disease control also in selected patients with unfavorable patterns of spread. The beneficial effect of whole-brain radiotherapy is not necessarily limited to symptom palliation.}, } @article {pmid28856027, year = {2017}, author = {Nasralla, AM and Al-Duhileb, MA and Arini, AJ and Amr, SS}, title = {Cutaneous Erythema at Scar Site of Modified Radical Mastectomy: An Unexpected Manifestation of Recurrent Carcinoma.}, journal = {Case reports in surgery}, volume = {2017}, number = {}, pages = {6879626}, pmid = {28856027}, issn = {2090-6900}, abstract = {A 44-year-old woman presented with marked erythema over right mastectomy scar, while on Herceptin therapy. She had neoadjuvant chemotherapy, modified radical mastectomy, and radiotherapy less than one year earlier for the treatment of invasive ductal carcinoma. On physical examination, no palpable masses were detected in the erythematous skin. A biopsy revealed permeation of the skin lymphatics by emboli of metastatic ductal carcinoma, similar to what is seen in inflammatory carcinoma. The involved skin was excised, followed by immediate reconstruction with transverse rectus abdominis muscle (TRAM) flap. On follow-up, the wound was healing well, with no signs of inflammation.}, } @article {pmid28855989, year = {2017}, author = {Zhang, H and Xiang, R and Wu, B and Li, J and Luo, G}, title = {T-cell immunoglobulin mucin-3 expression in invasive ductal breast carcinoma: Clinicopathological correlations and association with tumor infiltration by cytotoxic lymphocytes.}, journal = {Molecular and clinical oncology}, volume = {7}, number = {4}, pages = {557-563}, pmid = {28855989}, issn = {2049-9450}, abstract = {As a negative regulatory molecule, T-cell immunoglobulin and mucin domain-3 (Tim-3) is closely associated with tumor immunological tolerance. The aim of this study was to investigate Tim-3 expression in invasive ductal breast cancer (IDC), its effect on clinicopathological parameters and its association with cytotoxic lymphocyte infiltration. Tim-3 protein expression was measured in 150 paraffin-embedded IDC specimens and 100 paired normal breast tissue specimens by immunohistochemistry. It was demonstrated that the infiltration of the tumor by CD8[+] T cells was significantly higher compared with that of normal tissue, and the Tim-3 expression on CD8[+] T cells was higher in IDC tissue compared with that in normal tissue; the differences were statistically significant (both P-values=0.000). The median expression level of Tim-3 on tumor cells was significantly associated with clinicopathological parameters such as age, axillary lymph node metastasis and TNM stage (P=0.015, 0.001 and 0.027, respectively). The expression of Tim-3 on CD8[+] T cells was correlated with lymph node metastasis, World Health Organization (WHO) grade and molecular classification (P=0.000, 0.004 and 0.000, respectively). Additionally, the number of tumor-infiltrating CD8[+] T cells was associated with primary tumor size, lymph node metastasis, WHO grade, Ki-67 and molecular classification (P=0.017, 0.002, 0.007, 0.003 and 0.000, respectively). Thus, Tim-3 may promote the development and progression of breast cancer and affect the tumor microenvironment; thus, it may be used as an independent prognostic factor for IDC patients.}, } @article {pmid28852451, year = {2017}, author = {Mann, N and Ma, T and Dalton, A}, title = {Neurofibromatosis type 1 and male breast cancer: emerging risk factor?.}, journal = {Journal of surgical case reports}, volume = {2017}, number = {7}, pages = {rjw138}, pmid = {28852451}, issn = {2042-8812}, abstract = {Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by the appearance of cafe au lait spots, neurofibromas and Lisch nodules. There is an established link between NF1 and the development of breast cancer in women; however, due to the rarity of both NF1 and male breast cancer, the same link has yet to be elucidated in men. The concurrent presentation of NF1 and male breast cancer is a very rare phenomenon with only a handful of case descriptions in the literature. To the best of our knowledge, there have only been four other reported cases of NF1 and male breast cancer before ours. We present one such case of a 56-year-old male with a four generation history of NF1 and a personal history of NF1 who presented with invasive ductal carcinoma of the right breast.}, } @article {pmid28844697, year = {2017}, author = {Hamada, Y and Nakayama, Y}, title = {Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {17}, number = {6}, pages = {951-955}, doi = {10.1016/j.pan.2017.08.006}, pmid = {28844697}, issn = {1424-3911}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Female ; Humans ; Liver/pathology ; Liver Neoplasms/*secondary ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms/*pathology ; }, abstract = {BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors.

METHODS: Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2 cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years.

RESULTS: The small-tumor group (n = 20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n = 5) and 15 patients (non-LM group, n = 15) were either alive without recurrence (n = 11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n = 1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group.

CONCLUSION: Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM.}, } @article {pmid28843709, year = {2018}, author = {Karnik, T and Kimler, BF and Fan, F and Tawfik, O}, title = {PD-L1 in breast cancer: comparative analysis of 3 different antibodies.}, journal = {Human pathology}, volume = {72}, number = {}, pages = {28-34}, doi = {10.1016/j.humpath.2017.08.010}, pmid = {28843709}, issn = {1532-8392}, mesh = {Antibodies, Monoclonal/immunology/*therapeutic use ; B7-H1 Antigen/*immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*drug therapy/immunology ; Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology ; Immunohistochemistry/methods ; Lung Neoplasms/*drug therapy/immunology/pathology ; Treatment Outcome ; }, abstract = {The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.}, } @article {pmid28830512, year = {2017}, author = {Gupta, AP and Zhu, L and Tripathi, J and Kucharski, M and Patra, A and Bozdech, Z}, title = {Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum.}, journal = {Epigenetics & chromatin}, volume = {10}, number = {1}, pages = {40}, pmid = {28830512}, issn = {1756-8935}, mesh = {Acetylation ; *Cell Proliferation ; Chromatin/metabolism ; Erythrocytes/parasitology ; Histones/*metabolism ; *Host-Parasite Interactions ; Humans ; Open Reading Frames ; Plasmodium falciparum/*genetics/pathogenicity ; Promoter Regions, Genetic ; *Protein Processing, Post-Translational ; Protozoan Proteins/*metabolism ; }, abstract = {BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum.

RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5' end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region.

CONCLUSIONS: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite-host interaction both of which play a major role in malaria parasite virulence.}, } @article {pmid28826004, year = {2017}, author = {Zemva, J and Fink, CA and Fleming, TH and Schmidt, L and Loft, A and Herzig, S and Knieß, RA and Mayer, M and Bukau, B and Nawroth, PP and Tyedmers, J}, title = {Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.}, journal = {Redox biology}, volume = {13}, number = {}, pages = {674-686}, pmid = {28826004}, issn = {2213-2317}, mesh = {Amino Acid Transport Systems/metabolism ; *Energy Metabolism ; Glucose/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; *Hormesis ; Pyruvaldehyde/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells.}, } @article {pmid28818676, year = {2017}, author = {Shai, D and Dollberg, D and Szepsenwol, O}, title = {The importance of parental verbal and embodied mentalizing in shaping parental experiences of stress and coparenting.}, journal = {Infant behavior & development}, volume = {49}, number = {}, pages = {87-96}, doi = {10.1016/j.infbeh.2017.08.003}, pmid = {28818676}, issn = {1934-8800}, mesh = {Adult ; Child Development ; Female ; Humans ; Infant ; Infant Behavior/*physiology ; Male ; Mothers/psychology ; *Object Attachment ; Parenting/psychology ; Parents/*psychology ; Self Report ; Theory of Mind ; *Verbal Behavior ; }, abstract = {Parental mentalizing-recognizing that children are separate psychological entities, who have their own thoughts, wishes, and intentions that motivate their behaviors-is traditionally considered a verbal, linguistic capacity. This paper aimed to examine the relation between parental verbal mentalizing (parental reflective function; PRF) and its nonverbal form-parental embodied mentalizing (PEM)-and how both constructs contribute to parents' subjective experience of parenting, namely parental stress and coparental alliance. 68 mothers and their three-months-old babies were observed to assess PEM, interviewed to code PRF, and completed self-reports of coparental alliance and parental stress. PEM was found to be positively correlated with PRF. Mediation analyses revealed that higher PEM, but not PRF, was associated with lower parental stress, mediated by positive reports of coparental alliance. The findings support adopting a multifaceted approach when studying parental mentalizing, both in terms of assessing parental mentalizing beyond its verbal expressions to include also embodied aspects, as well as investigating its impact beyond infant development to include the familial context within it operates. Conceptual, empirical and clinical implications are discussed.}, } @article {pmid28816144, year = {2017}, author = {Leonardi, MC and Maisonneuve, P and Mastropasqua, MG and Cattani, F and Fanetti, G and Morra, A and Lazzari, R and Bazzani, F and Caputo, M and Rotmensz, N and Gerardi, MA and Ricotti, R and Enrica Galimberti, V and Veronesi, P and Dicuonzo, S and Viale, G and Jereczek-Fossa, BA and Orecchia, R}, title = {Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.}, journal = {International journal of radiation oncology, biology, physics}, volume = {99}, number = {1}, pages = {173-181}, doi = {10.1016/j.ijrobp.2017.04.033}, pmid = {28816144}, issn = {1879-355X}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/epidemiology/pathology/*radiotherapy/surgery ; Carcinoma, Lobular/epidemiology/pathology/*radiotherapy/surgery ; Case-Control Studies ; Electrons/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Incidence ; Intraoperative Period ; Kaplan-Meier Estimate ; Mastectomy, Segmental/statistics & numerical data ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology ; Propensity Score ; Radiotherapy/methods/statistics & numerical data ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC).

METHODS AND MATERIALS: From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control.

RESULTS: Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control.

CONCLUSIONS: Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control.}, } @article {pmid28801774, year = {2017}, author = {Escórcio-Dourado, CS and Martins, LM and Simplício-Revoredo, CM and Sampaio, FA and Tavares, CB and da Silva-Sampaio, JP and Borges, US and Alves-Ribeiro, FA and Lopes-Costa, PV and Lima-Dourado, JC and da Silva, BB}, title = {Bcl-2 antigen expression in luminal A and triple-negative breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {34}, number = {9}, pages = {161}, pmid = {28801774}, issn = {1559-131X}, mesh = {Adult ; Antigens/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*immunology/metabolism ; Triple Negative Breast Neoplasms/*immunology/*pathology ; }, abstract = {Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.}, } @article {pmid28799130, year = {2017}, author = {Banerjee, S and Saha, M and Arun, I and Basak, B and Agarwal, S and Ahmed, R and Chatterjee, S and Mahanta, LB and Chakraborty, C}, title = {Near-set Based Mucin Segmentation in Histopathology Images for Detecting Mucinous Carcinoma.}, journal = {Journal of medical systems}, volume = {41}, number = {9}, pages = {144}, pmid = {28799130}, issn = {1573-689X}, mesh = {*Adenocarcinoma, Mucinous ; Color ; Humans ; Mucins ; }, abstract = {This paper introducesnear-set based segmentation method for extraction and quantification of mucin regions for detecting mucinouscarcinoma (MC which is a sub type of Invasive ductal carcinoma (IDC)). From histology point of view, the presence of mucin is one of the indicators for detection of this carcinoma. In order to detect MC, the proposed method majorly includes pre-processing by colour correction, colour transformation followed by near-set based segmentation and post-processing for delineating only mucin regions from the histological images at 40×. The segmentation step works in two phases such as Learn and Run.In pre-processing step, white balance method is used for colour correction of microscopic images (RGB format). These images are transformed into HSI (Hue, Saturation, and Intensity) colour space and H-plane is extracted in order to get better visual separation of the different histological regions (background, mucin and tissue regions). Thereafter, histogram in H-plane is optimally partitioned to find set representation for each of the regions. In Learn phase, features of typical mucin pixel and unlabeled pixels are learnt in terms of coverage of observed sets in the sample space surrounding the pixel under consideration. On the other hand, in Run phase the unlabeled pixels are clustered as mucin and non-mucin based on its indiscernibilty with ideal mucin, i.e. their feature values differ within a tolerance limit. This experiment is performed for grade-I and grade-II of MC and hence percentage of average segmentation accuracy is achieved within confidence interval of [97.36 97.70] for extracting mucin areas. In addition, computation of percentage of mucin present in a histological image is provided for understanding the alteration of such diagnostic indicator in MC detection.}, } @article {pmid28797564, year = {2017}, author = {D'Iorio, A and Vitale, C and Piscopo, F and Baiano, C and Falanga, AP and Longo, K and Amboni, M and Barone, P and Santangelo, G}, title = {Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {43}, number = {}, pages = {114-117}, doi = {10.1016/j.parkreldis.2017.08.003}, pmid = {28797564}, issn = {1873-5126}, mesh = {*Activities of Daily Living ; Anxiety/diagnosis/*etiology ; Apathy/*physiology ; Cognition Disorders/diagnosis/etiology ; Female ; Humans ; Male ; Neuropsychological Tests ; Parkinson Disease/*complications/*psychology ; Psychiatric Status Rating Scales ; Quality of Life/*psychology ; Severity of Illness Index ; Statistics as Topic ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD.

METHODS: Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied.

RESULTS: Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8.

CONCLUSIONS: The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD.}, } @article {pmid28796582, year = {2018}, author = {Beyrak-Lev, J and Gerber, Z and Ein-Dor, T and Hirschberger, G}, title = {Mortality salience reduces tactile attention among people with low body esteem.}, journal = {Death studies}, volume = {42}, number = {7}, pages = {426-431}, doi = {10.1080/07481187.2017.1363321}, pmid = {28796582}, issn = {1091-7683}, mesh = {Adult ; Attention/*physiology ; *Attitude to Death ; Body Image/*psychology ; Female ; Humans ; Male ; Touch Perception/*physiology ; Visual Perception/*physiology ; Young Adult ; }, abstract = {Death awareness leads to aversion from bodily processes such as breastfeeding and sex, especially among low body esteem individuals. Using a modality bias task, we examined whether primes of death reduced attention to bodily sensations. We subliminally primed 72 undergraduates with either the word death or failed and assessed their attention to tactile and visual stimuli as a function of their body esteem. Results indicated that death primes significantly reduced attention to tactile stimuli relative to visual stimuli in low body esteem individuals. Dissociation from the body, therefore, may be an unconscious terror management strategy utilized by people with low body esteem.}, } @article {pmid28795370, year = {2017}, author = {Grimm, LJ and Ryser, MD and Partridge, AH and Thompson, AM and Thomas, JS and Wesseling, J and Hwang, ES}, title = {Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials.}, journal = {Annals of surgical oncology}, volume = {24}, number = {12}, pages = {3534-3540}, pmid = {28795370}, issn = {1534-4681}, support = {K99 CA207872/CA/NCI NIH HHS/United States ; R00 CA207872/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; *Clinical Trials as Topic ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Patient Selection ; Prognosis ; Retrospective Studies ; Vacuum ; }, abstract = {PURPOSE: This study was designed to determine invasive cancer upstaging rates at surgical excision following vacuum-assisted biopsy of ductal carcinoma in situ (DCIS) among women meeting eligibility for active surveillance trials.

METHODS: Patients with vacuum-assisted, biopsy-proven DCIS at a single center from 2008 to 2015 were retrospectively reviewed. Imaging and pathology reports were interrogated for the imaging appearance, tumor grade, hormone receptor status, and presence of comedonecrosis. Subsequent surgical reports were reviewed for upstaging to invasive disease. Cases were classified by eligibility criteria for the COMET, LORIS, and LORD DCIS active surveillance trials.

RESULTS: Of 307 DCIS diagnoses, 15 (5%) were low, 95 (31%) intermediate, and 197 (64%) high nuclear grade. The overall upstage rate to invasive disease was 17% (53/307). Eighty-one patients were eligible for the COMET Trial, 74 for the LORIS trial, and 10 for the LORD Trial, although LORIS trial eligibility also included real-time, multiple central pathology review, including elements not routinely reported. The upstaging rates to invasive disease were 6% (5/81), 7% (5/74), and 10% (1/10) for the COMET, LORIS, and LORD trials, respectively. Among upstaged cancers (n = 5), four tumors were Stage IA invasive ductal carcinoma and one was Stage IIA invasive lobular carcinoma; all were node-negative.

CONCLUSIONS: DCIS upstaging rates in women eligible for active surveillance trials are low (6-10%), and in this series, all those with invasive disease were early-stage, node-negative. The careful patient selection for DCIS active surveillance trials has a low risk of missing occult invasive cancer and additional studies will determine clinical outcomes.}, } @article {pmid28793265, year = {2017}, author = {Niopek, K and Üstünel, BE and Seitz, S and Sakurai, M and Zota, A and Mattijssen, F and Wang, X and Sijmonsma, T and Feuchter, Y and Gail, AM and Leuchs, B and Niopek, D and Staufer, O and Brune, M and Sticht, C and Gretz, N and Müller-Decker, K and Hammes, HP and Nawroth, P and Fleming, T and Conkright, MD and Blüher, M and Zeigerer, A and Herzig, S and Berriel Diaz, M}, title = {A Hepatic GAbp-AMPK Axis Links Inflammatory Signaling to Systemic Vascular Damage.}, journal = {Cell reports}, volume = {20}, number = {6}, pages = {1422-1434}, doi = {10.1016/j.celrep.2017.07.023}, pmid = {28793265}, issn = {2211-1247}, mesh = {AMP-Activated Protein Kinase Kinases ; Animals ; Atherosclerosis/etiology/*metabolism/pathology ; Cell Line ; Cells, Cultured ; Cholesterol/metabolism ; GA-Binding Protein Transcription Factor/chemistry/*metabolism ; Hepatocytes/*metabolism ; Hypercholesterolemia/complications/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Protein Kinases/*metabolism ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Reactive Oxygen Species/metabolism ; *Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Increased pro-inflammatory signaling is a hallmark of metabolic dysfunction in obesity and diabetes. Although both inflammatory and energy substrate handling processes represent critical layers of metabolic control, their molecular integration sites remain largely unknown. Here, we identify the heterodimerization interface between the α and β subunits of transcription factor GA-binding protein (GAbp) as a negative target of tumor necrosis factor alpha (TNF-α) signaling. TNF-α prevented GAbpα and β complex formation via reactive oxygen species (ROS), leading to the non-energy-dependent transcriptional inactivation of AMP-activated kinase (AMPK) β1, which was identified as a direct hepatic GAbp target. Impairment of AMPKβ1, in turn, elevated downstream cellular cholesterol biosynthesis, and hepatocyte-specific ablation of GAbpα induced systemic hypercholesterolemia and early macro-vascular lesion formation in mice. As GAbpα and AMPKβ1 levels were also found to correlate in obese human patients, the ROS-GAbp-AMPK pathway may represent a key component of a hepato-vascular axis in diabetic long-term complications.}, } @article {pmid28791792, year = {2018}, author = {Aardema, F and Moulding, R and Melli, G and Radomsky, AS and Doron, G and Audet, JS and Purcell-Lalonde, M}, title = {The role of feared possible selves in obsessive-compulsive and related disorders: A comparative analysis of a core cognitive self-construct in clinical samples.}, journal = {Clinical psychology & psychotherapy}, volume = {25}, number = {1}, pages = {e19-e29}, doi = {10.1002/cpp.2121}, pmid = {28791792}, issn = {1099-0879}, mesh = {Adult ; *Cognition ; *Ego ; Fear/*psychology ; Female ; Humans ; Male ; Obsessive-Compulsive Disorder/*psychology ; Psychometrics ; *Self Concept ; Surveys and Questionnaires ; }, abstract = {Increasingly, cognitive-behavioural models have been considering the role of beliefs about the self in the development and maintenance of obsessive-compulsive disorder (OCD), including sensitive domains of self-concept and feared self-perceptions. This has led to the development of the Fear of Self Questionnaire (FSQ; Aardema et al.,), which has shown strong internal consistency, divergent and convergent validity, and found to be a major predictor of unwanted thoughts and impulses (i.e., repugnant obsessions). The current study aimed to investigate fear of self-perceptions using the FSQ in an OCD sample (n = 144) and related psychological disorders (eating disorders, n = 57; body dysmorphic disorder, n = 33) in comparison to a non-clinical (n = 141) and clinical comparison group (anxiety/depressive disorders, n = 27). Following an exploratory factor analysis of the scale in the OCD sample, the results showed that participants with OCD in general did not score significantly higher on fear of self-perceptions than did the clinical comparison participants. However, consistent with previous findings, fear of self was highly characteristic among OCD patients with unwanted repugnant thoughts and impulses. In addition, fear of self-perceptions were significantly more elevated in those with eating or body dysmorphic disorders relative to the other non-clinical and clinical groups. The construct of a "feared possible self" may be particularly relevant in disorders where negative self-perception is a dominant theme, either involving concerns about one's inner self or concerns related to perceived bodily faults.}, } @article {pmid28791367, year = {2017}, author = {Zheng, T and Wang, A and Hu, D and Wang, Y}, title = {Molecular mechanisms of breast cancer metastasis by gene expression profile analysis.}, journal = {Molecular medicine reports}, volume = {16}, number = {4}, pages = {4671-4677}, pmid = {28791367}, issn = {1791-3004}, mesh = {Breast Neoplasms/*genetics/immunology/metabolism/*pathology ; Cell Adhesion/genetics ; Computational Biology/methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Molecular Sequence Annotation ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Protein Interaction Mapping ; Protein Interaction Maps ; *Transcriptome ; }, abstract = {Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software. The resulting data were used in subsequent function and pathway enrichment analyses, as well as protein‑protein interaction (PPI) network and subnetwork analyses. Transcription factors (TFs) and tumor‑associated genes were also identified among the DEGs. A total of 234 DEGs were identified, which were enriched in immune response, cell differentiation and cell adhesion‑related functions and pathways. Downregulated DEGs included TFs, such as the proto‑oncogene SPI1, pre‑B‑cell leukemia homeobox 3 (PBX3) and lymphoid enhancer‑binding factor 1 (LEF1), as well as tumor suppressors (TSs), such as capping actin protein, gelsolin like (CAPG) and tumor protein p53‑inducible nuclear protein 1 (TP53INP1). Upregulated DEGs also included TFs and tumor suppressors, consisting of transcription factor 7‑like 2 (TCF7L2) and pleiomorphic adenoma gene‑like 1 (PLAGL1). DEGs that were identified at the hub nodes in the PPI network and the subnetwork were epidermal growth factor receptor (EGFR) and spleen‑associated tyrosine kinase (SYK), respectively. Several genes crucial in the metastasis of breast cancer were identified, which may serve as potential biomarkers, many of which were associated with cell adhesion, proliferation or immune response, and may influence breast cancer metastasis by regulating these function or pathways.}, } @article {pmid28781782, year = {2017}, author = {Fujii, T and Yajima, R and Tatsuki, H and Kuwano, H}, title = {[18]F-fluorodeoxyglucose uptake as predictor for invasion in preoperatively diagnosed breast ductal carcinoma in situ: Significance in cases without mass formation.}, journal = {Molecular and clinical oncology}, volume = {7}, number = {2}, pages = {183-187}, pmid = {28781782}, issn = {2049-9450}, abstract = {A diagnosis of ductal carcinoma in situ (DCIS) at needle biopsy often changes to that of invasive ductal carcinoma as the definitive pathological diagnosis following the surgical procedure. The present study sought to identify the factors associated with invasive disease in cases diagnosed as DCIS on needle biopsy by analyzing [18]F-fluorodeoxyglucose-proton emission tomography (FDG-PET) findings. The present study retrospectively investigated the cases of 24 consecutive patients with primary breast cancer who were preoperatively diagnosed with DCIS by needle biopsy. The cases were divided into two groups based on the presence of invasion in the primary tumor. Among the 24 patients, 13 (54.7%) patients had invasive carcinoma and 11 (45.8%) had DCIS. The analysis revealed that the presence of FDG uptake in the tumor was the only independent predictor of presence of the invasive disease. No cases without FDG uptake exhibited invasion and all of these were ultimately diagnosed as DCIS. In the present study, all cases, including DCIS, with a nodular growth pattern demonstrated FDG uptake in the tumors, and all cases without FDG uptake were interpreted as having a diffuse growth pattern. The present findings suggested that the presence of FDG uptake in the tumor can be considered a predictor for invasion in cases with DCIS by needle biopsy, particularly in cases with a diffuse growth pattern. Patients preoperatively diagnosed as DCIS without mass formation and without FDG uptake in the tumor may avoid sentinel lymph node biopsy.}, } @article {pmid28780646, year = {2017}, author = {Borges, US and Costa-Silva, DR and da Silva-Sampaio, JP and Escórcio-Dourado, CS and Conde, AM and Campelo, V and Gebrim, LH and da Silva, BB and Lopes-Costa, PV}, title = {A comparative study of Ki-67 antigen expression between luminal A and triple-negative subtypes of breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {34}, number = {9}, pages = {156}, pmid = {28780646}, issn = {1559-131X}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Cell Proliferation/physiology ; Cross-Sectional Studies ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/*metabolism ; }, abstract = {Tumor biomarkers such as hormone receptors, HER-2 and Ki-67 are used routinely in clinical practice for classification of molecular subtypes of breast cancer. Cell proliferation evaluated by Ki-67 antigen expression is important to determine tumor aggressiveness. However, there is a paucity of studies comparing Ki-67 expression in an expressive number of cells among molecular subtypes of breast cancer, particularly among less and more aggressive tumors, such as luminal A and triple-negative, which have led us to the present study. The current study included invasive ductal carcinoma samples of 59 patients, which were divided into two groups: luminal A (n = 29) and triple-negative (n = 30). For immunohistochemical reaction, the samples were incubated with monoclonal anti-Ki-67 antibody (clone MIB1) and cells expressing Ki-67 protein were identified by dark brown staining of the nuclei, counting at least 600 cells per slide. The mean percentages of stained nuclei were analyzed by Student's t test (p < 0.05). The mean percentage of nuclei stained with anti-ki-67 was 10.14 and 77.22 in luminal A and triple-negative breast cancers, respectively (p < 0.0001). Our study showed a high cell proliferation of triple-negative breast cancer in comparison with luminal A, justifying its aggressiveness and poor clinical outcome.}, } @article {pmid28778882, year = {2017}, author = {Pfaff, DH and Fleming, T and Nawroth, P and Teleman, AA}, title = {Reply to Richarme: Evidence against a role of DJ-1 in methylglyoxal detoxification.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {31}, pages = {12784-12785}, pmid = {28778882}, issn = {1083-351X}, mesh = {Humans ; *Oncogene Proteins ; Protein Deglycase DJ-1/*physiology ; *Pyruvaldehyde ; }, } @article {pmid28778029, year = {2017}, author = {Watanabe, M and Matsuoka, R and Ichimura, Y and Takagaki, T and Iitsuka, Y}, title = {Papillotubular carcinoma with an invasive micropapillary carcinoma component of the breast, characterized by a rapid increase in size due to intra-tumoral hemorrhage: A case report.}, journal = {International journal of surgery case reports}, volume = {38}, number = {}, pages = {189-191}, pmid = {28778029}, issn = {2210-2612}, abstract = {INTRODUCTION: Rapidly enlarging mammary tumors, including invasive breast tumors, are clinically rare. Invasive micropapillary carcinoma (IMPC) of the breast is known to have aggressive behavior and poor clinical course compared to invasive ductal carcinoma.

CASE PRESENTATION: An 87-year-old woman presented with a rapidly enlarging tumor of the right breast over the course of 3 weeks. Ultrasonography and computed tomography of the chest revealed a giant tumor located on the right chest wall, with heterogeneous parenchymal components and several cystic lesions. Emergency mastectomy was performed because of rapid tumor enlargement complicated by hemorrhage. Histopathological diagnosis confirmed a papillotubular invasive ductal carcinoma with an IMPC component. Tumor cells were negative for estrogen and progesterone receptors, and the human epidermal growth factor receptor 2 score was 2+.

DISCUSSION: There has been only one report of breast carcinoma with rapid enlargement caused by spontaneous intratumoral hemorrhage to date. IMPC is associated with a high incidence of axillary lymph node metastases, frequent local recurrence, and a poor clinical outcome. In the present case, the specific breast cancer type can be considered as potential factors responsible for hemorrhage induction within the tumor that further enhanced rapid tumor growth.

CONCLUSION: IMPC is a rare, clinically aggressive variant of invasive ductal carcinoma. Owing to its aggressive clinical behaviors, surgeons should readily recognize the morphology of IMPC.}, } @article {pmid28767583, year = {2017}, author = {Yoo, J and Kim, BS and Chung, J and Yoon, HJ}, title = {Percentage change of primary tumor on 18F-FDG PET/CT as a prognostic factor for invasive ductal breast cancer with axillary lymph node metastasis: Comparison with MRI.}, journal = {Medicine}, volume = {96}, number = {31}, pages = {e7657}, pmid = {28767583}, issn = {1536-5964}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/surgery ; Contrast Media ; Diffusion Magnetic Resonance Imaging ; Disease-Free Survival ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis/*diagnostic imaging ; Middle Aged ; Multivariate Analysis ; *Positron Emission Tomography Computed Tomography ; Prognosis ; *Radiopharmaceuticals ; Regression Analysis ; Retrospective Studies ; }, abstract = {We evaluated the prognostic value of quantitative parameters using dual time point (DTP) F-FDG PET/CT (PET/CT) in invasive ductal breast cancer (IDC) with metastatic axillary lymph nodes (ALN) as compared with dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI.Seventy patients with IDC and metastatic ALN were retrospectively registered. Static PET parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of primary tumor, SUVmax of ALN (SUVALN), and percentage changes (Δ%) in those parameters were measured with DTP PET/CT. From DCE MRI, peak enhancement value, total tumor angio volume, and proportions of kinetic curve types on delayed-phases were investigated. The average apparent diffusion coefficient (ADCavg) was estimated on DWI. To demonstrate the prognostic value of quantitative imaging parameters for recurrence-free survival (RFS), univariate and multivariate analyses were performed using those parameters and clinicohistologic variables.All static PET parameters, %ΔSUVmax, %ΔMTV, and %ΔSUVALN on DTP PET/CT and ADCavg on DWI were significantly predictive for disease recurrence. Of clinicohistologic variables, pathologic tumor (pT) diameter, pathologic ALN stage, tumor grade, and hormonal status also were significantly prognostic. After multivariate analysis, %ΔSUVmax > 25.05 (P = .043), ADCavg ≤ 1016.55 (P = .020), pT diameter > 3 cm (P = .001), and ER negative status (P = .002) were independent prognostic factors for poor outcome.Only %ΔSUVmax of the primary tumor on PET/CT together with ADCavg, pT diameter, and ER status was an independent prognostic factor for predicting relapse in IDC with metastatic ALN. Percentage change of primary tumor on preoperative PET/CT may be a valuable imaging marker for selecting IDC patients that require adjunct treatment to prevent relapse.}, } @article {pmid28765906, year = {2017}, author = {Wang, J and Song, L and Yang, S and Zhang, W and Lu, P and Li, S and Li, H and Wang, L}, title = {HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.}, journal = {Molecular medicine reports}, volume = {16}, number = {4}, pages = {4634-4642}, pmid = {28765906}, issn = {1791-3004}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/*mortality/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; }, abstract = {Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma‑not otherwise specified (IDC‑NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC‑NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC‑NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC‑NOS were detected using immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1‑positive, and 100 out of 148 (67.6%) were ER‑positive. Of the latter, 28% (28/100) were HPK1‑positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=‑0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC‑NOS tissues were PR‑ or HER2‑positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC‑NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC‑NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.}, } @article {pmid28764784, year = {2017}, author = {Liu, JB and Feng, CY and Deng, M and Ge, DF and Liu, DC and Mi, JQ and Feng, XS}, title = {E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis.}, journal = {World journal of surgical oncology}, volume = {15}, number = {1}, pages = {139}, pmid = {28764784}, issn = {1477-7819}, mesh = {Adult ; Antigens, CD ; Breast Neoplasms/*pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Phenotype ; Prognosis ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {BACKGROUND: This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC).

METHODS: A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics.

RESULTS: E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P < 0.050); moreover, the molecular subtypes were an independent factor influencing E-cad expression in early-stage IDCs. A total of 12 observational studies (including our study) were included in the meta-analysis. The meta-analytical results show a significantly greater risk of E-cad expression loss in triple-negative breast cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07).

CONCLUSIONS: Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.}, } @article {pmid28764176, year = {2017}, author = {Kumar, M and Pottipati, B and Arakeri, SU and Javalgi, AP}, title = {Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {11}, number = {6}, pages = {ED04-ED05}, pmid = {28764176}, issn = {2249-782X}, abstract = {Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.}, } @article {pmid28760730, year = {2017}, author = {Tziraki, C and Berenbaum, R and Gross, D and Abikhzer, J and Ben-David, BM}, title = {Designing Serious Computer Games for People With Moderate and Advanced Dementia: Interdisciplinary Theory-Driven Pilot Study.}, journal = {JMIR serious games}, volume = {5}, number = {3}, pages = {e16}, pmid = {28760730}, issn = {2291-9279}, abstract = {BACKGROUND: The field of serious games for people with dementia (PwD) is mostly driven by game-design principals typically applied to games created by and for younger individuals. Little has been done developing serious games to help PwD maintain cognition and to support functionality.

OBJECTIVES: We aimed to create a theory-based serious game for PwD, with input from a multi-disciplinary team familiar with aging, dementia, and gaming theory, as well as direct input from end users (the iterative process). Targeting enhanced self-efficacy in daily activities, the goal was to generate a game that is acceptable, accessible and engaging for PwD.

METHODS: The theory-driven game development was based on the following learning theories: learning in context, errorless learning, building on capacities, and acknowledging biological changes-all with the aim to boost self-efficacy. The iterative participatory process was used for game screen development with input of 34 PwD and 14 healthy community dwelling older adults, aged over 65 years. Development of game screens was informed by the bio-psychological aging related disabilities (ie, motor, visual, and perception) as well as remaining neuropsychological capacities (ie, implicit memory) of PwD. At the conclusion of the iterative development process, a prototype game with 39 screens was used for a pilot study with 24 PwD and 14 healthy community dwelling older adults. The game was played twice weekly for 10 weeks.

RESULTS: Quantitative analysis showed that the average speed of successful screen completion was significantly longer for PwD compared with healthy older adults. Both PwD and controls showed an equivalent linear increase in the speed for task completion with practice by the third session (P<.02). Most important, the rate of improved processing speed with practice was not statistically different between PwD and controls. This may imply that some form of learning occurred for PwD at a nonsignificantly different rate than for controls. Qualitative results indicate that PwD found the game engaging and fun. Healthy older adults found the game too easy. Increase in self-reported self-efficacy was documented with PwD only.

CONCLUSIONS: Our study demonstrated that PwD's speed improved with practice at the same rate as healthy older adults. This implies that when tasks are designed to match PwD's abilities, learning ensues. In addition, this pilot study of a serious game, designed for PwD, was accessible, acceptable, and enjoyable for end users. Games designed based on learning theories and input of end users and a multi-disciplinary team familiar with dementia and aging may have the potential of maintaining capacity and improving functionality of PwD. A larger longer study is needed to confirm our findings and evaluate the use of these games in assessing cognitive status and functionality.}, } @article {pmid28757653, year = {2017}, author = {Mathew, A and Rajagopal, PS and Villgran, V and Sandhu, GS and Jankowitz, RC and Jacob, M and Rosenzweig, M and Oesterreich, S and Brufsky, A}, title = {Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast.}, journal = {Geburtshilfe und Frauenheilkunde}, volume = {77}, number = {6}, pages = {660-666}, pmid = {28757653}, issn = {0016-5751}, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) comprises around 10 - 15% of invasive breast cancers. Few prior studies have demonstrated a unique pattern of metastases between ILC and the more common invasive ductal carcinoma (IDC). To our knowledge, such data is limited to first sites of distant recurrence. We aimed to perform a comparison of the metastatic pattern of ILC and IDC at first distant recurrence as well as over the entire course of metastatic disease.

METHODS: We used a prospectively collated database of patients with metastatic breast cancer. Breast cancer recurrence or metastases were classified into various sites and a descriptive analysis was performed.

RESULTS: Among 761 patients, 88 (11.6%) were diagnosed with ILC and 673 (88.4%) with IDC. Patients with ILC showed more frequent metastases to the bone (56.8 vs. 37.7%, p = 0.001) and gastrointestinal (GI) tract (5.7 vs. 0.3%, p < 0.001) as first site of distant recurrence, and less to organs such as lung (5.7 vs. 24.2%, p < 0.001) and liver (4.6 vs. 11.4%, p = 0.049). Over the entire course of metastatic disease, more patients with ILC had ovarian (5.7 vs. 2.1%, p = 0.042) and GI tract metastases (8.0 vs. 0.6%, p < 0.001), also demonstrating reduced tendency to metastasize to the liver (20.5 vs. 49.0%, p < 0.001) and lung (23.9 vs. 51.9%, p < 0.001). All associations but bone held after sensitivity analysis on hormonal status. Although patients presenting with ILC were noted to have more advanced stage at presentation, recurrence-free survival in these patients was increased (4.8 years vs. 3.2 years, p = 0.017). However, overall survival was not (2.5 vs. 2.0 years, p = 0.75).

CONCLUSION: After accounting for hormone receptor status, patients with IDC had greater lung/pleura and liver involvement, while patients with ILC had a greater propensity to develop ovarian and GI metastases both at first site and overall. Clinicians can use this information to provide more directed screening for metastases; it also adds to the argument that these two variants of breast cancer should be managed as unique diseases.}, } @article {pmid28756987, year = {2017}, author = {Yan, Q and Xiaorong, Z and Zhang, Z and Bing, W and Feng, Y and Hong, B}, title = {Prevalence of protein C receptor (PROCR) is associated with inferior clinical outcome in Breast invasive ductal carcinoma.}, journal = {Pathology, research and practice}, volume = {213}, number = {9}, pages = {1173-1179}, doi = {10.1016/j.prp.2017.06.014}, pmid = {28756987}, issn = {1618-0631}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Endothelial Protein C Receptor/analysis/*biosynthesis ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prevalence ; Proportional Hazards Models ; }, abstract = {Recently, PROCR is reported to play an important role in cell growth, apoptosis, proliferation and tumor relapse. Some researchers thought that PROCR[+] cells had cancer stem cell ability, which might contribute to progressive behavior in breast cancer. Our study was to assess the expression of PROCR in invasive ductal carcinoma tissues with their prognostic implications. We enrolled formalin fixed paraffin-embedded tumor tissues of 271 patients diagnosed as invasive ductal breast cancer with clinical stage II or III into our study. Immunohistochemistry staining was performed on all the tissue microarray slides, and result were interpreted by two pathologists with blinded method. We analyzed PROCR expression levels with the clinical characteristics as well as their prognostic values. PROCR expression detected in the cell was interpreted. Chi-square test showed us its positive expression had a close association with distant metastases (p=0.035). Univariate survival analysis indicated that prevalence of PROCR expression in the invasive ductal breast cancer was significantly related with decreased disease-free survival (pDFS=0.010) and overall survival (pOS=0.008). In multivariate survival by Cox proportional hazard model, positive expression group for PROCR was found to have shorter DFS [pDFS=0.028, hazard ratio (95% CI): 1.183(1.069-3.140)]. Our findings suggested that breast cancer patients with expression of PROCR is more prone to suffer from distant metastasis and bad clinical outcomes.}, } @article {pmid28755148, year = {2017}, author = {Meng, F and Liu, B and Xie, G and Song, Y and Zheng, X and Qian, X and Li, S and Jia, H and Zhang, X and Zhang, L and Yang, YL and Fu, L}, title = {Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.}, journal = {Breast cancer research and treatment}, volume = {166}, number = {2}, pages = {383-392}, doi = {10.1007/s10549-017-4407-1}, pmid = {28755148}, issn = {1573-7217}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*genetics/*metabolism ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Papillary/genetics/*metabolism ; Cell Adhesion Molecules/metabolism ; Chromosomes, Human, Pair 8/genetics ; Female ; GPI-Linked Proteins/genetics/metabolism ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Proteins/*genetics/*metabolism ; Prognosis ; Survival Analysis ; *Up-Regulation ; }, abstract = {PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied.

METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis.

RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant rate of the immunohistochemistry and FISH data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs = 0.687, P < 0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022).

CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.}, } @article {pmid28752051, year = {2017}, author = {Maida, A and Chan, JSK and Sjøberg, KA and Zota, A and Schmoll, D and Kiens, B and Herzig, S and Rose, AJ}, title = {Repletion of branched chain amino acids reverses mTORC1 signaling but not improved metabolism during dietary protein dilution.}, journal = {Molecular metabolism}, volume = {6}, number = {8}, pages = {873-881}, pmid = {28752051}, issn = {2212-8778}, support = {//CIHR/Canada ; }, mesh = {Adult ; Amino Acids, Branched-Chain/blood/*metabolism ; Animals ; Dietary Proteins/*metabolism ; Fibroblast Growth Factors/blood/metabolism ; Humans ; Liver/metabolism ; Male ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; }, abstract = {OBJECTIVE: Dietary protein dilution (PD) has been associated with metabolic advantages such as improved glucose homeostasis and increased energy expenditure. This phenotype involves liver-induced release of FGF21 in response to amino acid insufficiency; however, it has remained unclear whether dietary dilution of specific amino acids (AAs) is also required. Circulating branched chain amino acids (BCAAs) are sensitive to protein intake, elevated in the serum of obese humans and mice and thought to promote insulin resistance. We tested whether replenishment of dietary BCAAs to an AA-diluted (AAD) diet is sufficient to reverse the glucoregulatory benefits of dietary PD.

METHODS: We conducted AA profiling of serum from healthy humans and lean and high fat-fed or New Zealand obese (NZO) mice following dietary PD. We fed wildtype and NZO mice one of three amino acid defined diets: control, total AAD, or the same diet with complete levels of BCAAs (AAD + BCAA). We quantified serum AAs and characterized mice in terms of metabolic efficiency, body composition, glucose homeostasis, serum FGF21, and tissue markers of the integrated stress response (ISR) and mTORC1 signaling.

RESULTS: Serum BCAAs, while elevated in serum from hyperphagic NZO, were consistently reduced by dietary PD in humans and murine models. Repletion of dietary BCAAs modestly attenuated insulin sensitivity and metabolic efficiency in wildtype mice but did not restore hyperglycemia in NZO mice. While hepatic markers of the ISR such as P-eIF2α and FGF21 were unabated by dietary BCAA repletion, hepatic and peripheral mTORC1 signaling were fully or partially restored, independent of changes in circulating glucose or insulin.

CONCLUSIONS: Repletion of BCAAs in dietary PD is sufficient to oppose changes in somatic mTORC1 signaling but does not reverse the hepatic ISR nor induce insulin resistance in type 2 diabetes during dietary PD.}, } @article {pmid28746732, year = {2017}, author = {Yang, M and Bao, W and Zhang, X and Kang, Y and Haffty, B and Zhang, L}, title = {Short-term and long-term clinical outcomes of uncommon types of invasive breast cancer.}, journal = {Histopathology}, volume = {71}, number = {6}, pages = {874-886}, doi = {10.1111/his.13328}, pmid = {28746732}, issn = {1365-2559}, support = {P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Age Factors ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {AIMS: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are predominant and well-documented types of invasive breast cancer (IBC). We investigated the clinical outcomes of other types of IBC (i.e. uncommon IBC), which collectively account for Σ20% of all IBC cases, as these are largely unknown.

METHODS AND RESULTS: We identified all IBC cases diagnosed in 2004-2006 (n = 159 293) and 2010-2011 (n = 118 822) from the Surveillance, Epidemiology and End Results (SEER) database. Uncommon IBCs included mixed IDC and ILC (MDLC), IDC mixed with other types of carcinoma, ILC mixed with other types of carcinoma, and other-type breast cancers (OCs). We estimated overall survival (OS) and cancer-specific survival in multivariate regression models. As compared with IDC, MDLC was associated with an increased OS [adjusted hazard ratio (aHR) = 0.92, P < 0.001 at Σ10 years of follow-up; aHR = 0.88, P = 0.01 at Σ4 years of follow-up], whereas OCs were associated with a decreased OS (aHR = 1.06, P = 0.005 at Σ10 years of follow-up; aHR = 1.23, P < 0.001 at Σ4 years of follow-up). Women with other uncommon IBCs had an OS similar to those with IDC. Heterogeneity in survival was observed for some subtypes of OC, with better OS for women with MDLC and tubular carcinoma. Radiotherapy extended OS for all types of IBC in older women (≥50 years). For younger women (<50 years), radiotherapy improved OS in women with IDC, but not in those with ILC or uncommon IBC. Radiotherapy did not change cancer-specific survival of younger women with any IBC.

CONCLUSIONS: Uncommon IBCs have distinct patterns of prognosis and survival. The effectiveness of radiotherapy in women with uncommon IBC may differ by age. The underlying mechanisms warrant further studies.}, } @article {pmid28744423, year = {2017}, author = {Bonzano, E and Guenzi, M and Corvò, R}, title = {A Successful Therapeutic Challenge: Local Reirradiation of Breast Cancer with a Single Dose of 18 Gy Intraoperative Radiation Therapy (IORT).}, journal = {Cureus}, volume = {9}, number = {6}, pages = {e1376}, pmid = {28744423}, issn = {2168-8184}, abstract = {After standard treatment of primary breast cancer, local relapse can develop in a previously irradiated region. The decision to refer a patient for a second radiotherapy must be thoroughly evaluated due to the increased risk of side effects. We report a case of a 43-year-old Caucasian female with a history of left breast lumpectomy and radiation treatment in 1990 for an invasive ductal carcinoma who presented with a locoregional recurrence 19 years later. After careful evaluation, the patient has undergone a second breast-conserving surgery and successful reirradiation with 18 Gy single dose of intraoperative radiation therapy (IORT).}, } @article {pmid28733470, year = {2017}, author = {Kim, JT and Liu, Y and Kulkarni, RP and Lee, KK and Dai, B and Lovely, G and Ouyang, Y and Wang, P and Yang, L and Baltimore, D}, title = {Dendritic cell-targeted lentiviral vector immunization uses pseudotransduction and DNA-mediated STING and cGAS activation.}, journal = {Science immunology}, volume = {2}, number = {13}, pages = {}, pmid = {28733470}, issn = {2470-9468}, support = {KL2 TR001882/TR/NCATS NIH HHS/United States ; P30 AI028697/AI/NIAID NIH HHS/United States ; }, abstract = {Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro. Activation of DCs by LVs was independent of MyD88, TRIF, and MAVS, ruling out an involvement of Toll-like receptor or RIG-I-like receptor signaling. Cellular DNA packaged in LV preparations induced DC activation by the host STING (stimulator of interferon genes) and cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase) pathway. Envelope-mediated viral fusion also activated DCs in a phosphoinositide 3-kinase-dependent but STING-independent process. Pseudotransduction, transduction, viral fusion, and delivery of cellular DNA collaborate to make the DC-targeted LV preparation an effective immunogen.}, } @article {pmid28732472, year = {2017}, author = {Kulkarni, S and Jadhav, S and Khopkar, P and Sane, S and Londhe, R and Chimanpure, V and Dhilpe, V and Ghate, M and Yelagate, R and Panchal, N and Rahane, G and Kadam, D and Gaikwad, N and Rewari, B and Gangakhedkar, R}, title = {GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.}, journal = {BMC infectious diseases}, volume = {17}, number = {1}, pages = {506}, pmid = {28732472}, issn = {1471-2334}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Antiretroviral Therapy, Highly Active ; Case-Control Studies ; HIV Infections/*drug therapy/*virology ; *HIV-1/genetics/pathogenicity ; Humans ; India ; Point-of-Care Systems ; Real-Time Polymerase Chain Reaction/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Viral Load/*methods ; }, abstract = {BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings.

METHODS: A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure.

RESULTS: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p < 0.01), the linear regression showed a moderate fit (R[2] = 0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p = 0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R[2] = 0.896 to 0.982).

CONCLUSION: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.}, } @article {pmid28730339, year = {2017}, author = {Santiago, L and Adrada, BE and Huang, ML and Wei, W and Candelaria, RP}, title = {Breast cancer neoplastic seeding in the setting of image-guided needle biopsies of the breast.}, journal = {Breast cancer research and treatment}, volume = {166}, number = {1}, pages = {29-39}, doi = {10.1007/s10549-017-4401-7}, pmid = {28730339}, issn = {1573-7217}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/metabolism/mortality/*pathology ; Female ; Humans ; Image-Guided Biopsy ; Mammography ; Neoplasm Grading ; Neoplasm Seeding ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Triple Negative Breast Neoplasms/diagnostic imaging/metabolism/mortality/pathology ; }, abstract = {PURPOSE: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy.

METHODS: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS.

RESULTS: Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8 days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal.

CONCLUSION: High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.}, } @article {pmid28727493, year = {2018}, author = {Icht, M and Ben-David, BM}, title = {Sibilant production in Hebrew-speaking adults: Apical versus laminal.}, journal = {Clinical linguistics & phonetics}, volume = {32}, number = {3}, pages = {193-212}, doi = {10.1080/02699206.2017.1335780}, pmid = {28727493}, issn = {1464-5076}, mesh = {Adult ; Female ; Humans ; Israel ; Male ; *Palate ; *Phonetics ; Speech Acoustics ; Speech Production Measurement ; Speech Therapy/*methods ; Tongue/*physiology ; Young Adult ; }, abstract = {The Hebrew IPA charts describe the sibilants /s, z/ as 'alveolar fricatives', where the place of articulation on the palate is the alveolar ridge. The point of constriction on the tongue is not defined - apical (tip) or laminal (blade). Usually, speech and language pathologists (SLPs) use the apical placement in Hebrew articulation therapy. Some researchers and SLPs suggested that acceptable /s, z/ could be also produced with the laminal placement (i.e. the tip of the tongue approximating the lower incisors). The present study focused at the clinical level, attempting to determine the prevalence of these alternative points of constriction on the tongue for /s/ and /z/ in three different samples of Hebrew-speaking young adults (total n = 242), with typical articulation. Around 60% of the participants reported using the laminal position, regardless of several speaker-related variables (e.g. tongue-thrust swallowing, gender). Laminal production was more common in /s/ (than /z/), coda (than onset) position of the sibilant, mono- (than di-) syllabic words, and with non-alveolar (than alveolar) adjacent consonants. Experiment 3 revealed no acoustical differences between apical and laminal productions of /s/ and of /z/. From a clinical perspective, we wish to raise the awareness of SLPs to the prevalence of the two placements when treating Hebrew speakers, noting that tongue placements were highly correlated across sibilants. Finally, we recommend adopting a client-centred practice, where tongue placement is matched to the client. We further recommend selecting targets for intervention based on our findings, and separating between different prosodic positions in treatment.}, } @article {pmid28726282, year = {2017}, author = {Horikawa, H and Umegaki-Arao, N and Funakoshi, T and Amagai, M and Tanaka, M}, title = {Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma.}, journal = {The Australasian journal of dermatology}, volume = {58}, number = {4}, pages = {326-327}, doi = {10.1111/ajd.12671}, pmid = {28726282}, issn = {1440-0960}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Basal Cell/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; *Dermoscopy ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Nipples ; Skin Neoplasms/*diagnostic imaging/pathology/secondary ; Skin Pigmentation ; }, } @article {pmid28724885, year = {2017}, author = {Panko, N and Jebran, AA and Gomberawalla, A and Connolly, M}, title = {Invasive Ductal Carcinoma within a Benign Phyllodes Tumor.}, journal = {The American journal of case reports}, volume = {18}, number = {}, pages = {813-816}, pmid = {28724885}, issn = {1941-5923}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Neoplasms, Multiple Primary/*pathology ; Phyllodes Tumor/*pathology ; }, abstract = {BACKGROUND Phyllodes tumor (PT) is a rare neoplasm of the breast. Concomitant PT with invasive ductal carcinoma (IDC) is an even rarer occurrence. When ductal carcinoma in situ (DCIS) or IDC are detected within the specimen, the management changes from wide local excision to further staging work-up, including sentinel node biopsy and radiation. CASE REPORT We report the case of a 70-year-old presented with right breast mass whose pathology showed benign PT with concomitant IDC and DCIS. The patient elected for a wide excision of the mass with sentinel lymph node biopsy, which did not show any involvement. The patient was started on appropriate therapy. She is currently doing well. CONCLUSIONS This case highlights the importance of wide local excision for PT as well as prudent histologic examination to rule out other malignant components, as the presence of IDC distinctly changes management.}, } @article {pmid28722405, year = {2017}, author = {Liang, X and Li, B and Wang, M and Wang, J and Liu, R and Li, G}, title = {Effective Approach to Promoting the Proton Conductivity of Metal-Organic Frameworks by Exposure to Aqua-Ammonia Vapor.}, journal = {ACS applied materials & interfaces}, volume = {9}, number = {30}, pages = {25082-25086}, doi = {10.1021/acsami.7b07635}, pmid = {28722405}, issn = {1944-8252}, abstract = {We explored the proton conductivities of two 3D Co[II] metal-organic frameworks (MOFs), {[Co3(m-ClPhIDC)2(H2O)6]·2H2O} n [1; m-ClPhH3IDC = 2-(m-chlorophenyl)imidazole-4,5-dicarboxylic acid] and {[Co3(p-ClPhHIDC)3(H2O)3]·6H2O} n (2; p-ClPhH3IDC = 2-(p-chlorophenyl)imidazole-4,5-dicarboxylic acid), under water and aqua-ammonia vapors, respectively. The experimental results revealed that the proton conductivities of 1 and 2 at aqua-ammonia vapor were 2.89 × 10[-2] and 4.25 × 10[-2] S/cm, respectively, and approximately 2 orders of magnitude greater than those at water vapor. On the basis of the activation energy, water and ammonia vapor absorption, and powder X-ray diffraction patterns, their proton-conduction mechanisms have been discussed. We believe that this is a novel approach to drastically improving the proton conductivity of MOFs.}, } @article {pmid28719381, year = {2018}, author = {Oliveira, RV and Souza, VB and Souza, PC and Soares, FA and Vassallo, J and Rocha, RM and Schenka, AA}, title = {Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {26}, number = {10}, pages = {760-768}, pmid = {28719381}, issn = {1533-4058}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Brazil ; Breast Neoplasms/metabolism/mortality/pathology ; *Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Risk Factors ; Survival Rate ; }, abstract = {INTRODUCTION: Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined.

MATERIALS AND METHODS: An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated.

RESULTS: The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24/CD44 (CSC-1) and CD133/ESA (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69).

CONCLUSION: The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.}, } @article {pmid28717182, year = {2017}, author = {Bjørklund, SS and Panda, A and Kumar, S and Seiler, M and Robinson, D and Gheeya, J and Yao, M and Alnæs, GIG and Toppmeyer, D and Riis, M and Naume, B and Børresen-Dale, AL and Kristensen, VN and Ganesan, S and Bhanot, G}, title = {Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {5568}, pmid = {28717182}, issn = {2045-2322}, mesh = {*Alternative Splicing ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cohort Studies ; Databases, Genetic ; Exons ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Sequence Analysis, RNA/methods ; }, abstract = {Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2-, ER- HER2-, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2- and ER- HER2- primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2- and ER- HER2- patients, showing that these events were truly subtype specific.}, } @article {pmid28713304, year = {2017}, author = {Benedek, M and Stoiser, R and Walcher, S and Körner, C}, title = {Eye Behavior Associated with Internally versus Externally Directed Cognition.}, journal = {Frontiers in psychology}, volume = {8}, number = {}, pages = {1092}, pmid = {28713304}, issn = {1664-1078}, support = {P 29801/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {What do our eyes do when we are focused on internal representations such as during imagination or planning? Evidence from mind wandering research suggests that spontaneous shifts from externally directed cognition (EDC) to internally directed cognition (IDC) involves oculomotor changes indicative of visual disengagement. In the present study, we investigated potential differences in eye behavior between goal-directed forms of IDC and EDC. To this end, we manipulated the focus of attention (internal versus external) in two demanding cognitive tasks (anagram and sentence generation). IDC was associated with fewer and longer fixations and higher variability in pupil diameter and eye vergence compared to EDC, suggesting reduced visual scanning and higher spontaneous eye activity. IDC was further related to longer blinks, lower microsaccade frequency, and a lower angle of eye vergence. These latter changes appear conducive to attenuate visual input and thereby shield ongoing internal processes from external distraction. Together, these findings suggest that IDC is accompanied by characteristic eye behavior that reflects a decoupling of attention from external events and serves gating out visual input.}, } @article {pmid28712739, year = {2017}, author = {ALGhanem, A and Fernandes, G and Visser, M and Dziak, R and Renné, WG and Sabatini, C}, title = {Biocompatibility and bond degradation of poly-acrylic acid coated copper iodide-adhesives.}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {33}, number = {9}, pages = {e336-e347}, pmid = {28712739}, issn = {1879-0097}, support = {R41 DE026085/DE/NIDCR NIH HHS/United States ; }, mesh = {Acrylates ; *Copper ; Dental Bonding ; *Dental Cements ; Dentin ; Dentin-Bonding Agents ; Humans ; *Iodides ; Materials Testing ; *Resin Cements ; Tensile Strength ; }, abstract = {OBJECTIVE: To investigate the effect of poly-acrylic acid (PAA) copper iodide (CuI) adhesives on bond degradation, tensile strength, and biocompatibility.

METHODS: PAA-CuI particles were incorporated into Optibond XTR, Optibond Solo and XP Bond in 0.1 and 0.5mg/ml. Clearfil SE Protect, an MDPB-containing adhesive, was used as control. The adhesives were applied to human dentin, polymerized and restored with composite in 2mm-increments. Resin-dentin beams (0.9±0.1mm[2]) were evaluated for micro-tensile bond strength after 24h, 6 months and 1year. Hourglass specimens (10×2×1mm) were evaluated for ultimate tensile strength (UTS). Cell metabolic function of human gingival fibroblast cells exposed to adhesive discs (8×1mm) was assessed with MTT assay. Copper release from adhesive discs (5×1mm) was evaluated with UV-vis spectrophotometer after immersion in 0.9% NaCl for 1, 3, 5, 7, 10, 14, 21 and 30 days. SEM, EDX and XRF were conducted for microstructure characterization.

RESULTS: XTR and Solo did not show degradation when modified with PAA-CuI regardless of the concentration. The UTS for adhesives containing PAA-CuI remained unaltered relative to the controls. The percent viable cells were reduced for Solo 0.5mg/ml and XP 0.1 or 0.5mg/ml PAA-CuI. XP demonstrated the highest ion release. For all groups, the highest release was observed at days 1 and 14.

SIGNIFICANCE: PAA-CuI particles prevented the bond degradation of XTR and Solo after 1year without an effect on the UTS for any adhesive. Cell viability was affected for some adhesives. A similar pattern of copper release was demonstrated for all adhesives.}, } @article {pmid28710742, year = {2018}, author = {Avnon, A and Orkaby, N and Hadas, A and Berger, U and Brunstein Klomek, A and Fennig, S}, title = {Inpatient weight curve trajectory as a prognostic factor among adolescents with anorexia nervosa: a preliminary report.}, journal = {Eating and weight disorders : EWD}, volume = {23}, number = {5}, pages = {645-651}, pmid = {28710742}, issn = {1590-1262}, mesh = {Adolescent ; Anorexia Nervosa/physiopathology/*therapy ; Body Mass Index ; Body Weight/*physiology ; Child ; Female ; Humans ; *Inpatients ; Male ; Patient Discharge ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Weight Gain/*physiology ; }, abstract = {OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN.

METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1 year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV).

RESULTS: Logistic regression indicated that negative cubic variation rates (NCV) predicted re-hospitalization. PFTW was found only marginally significant.

CONCLUSION: Variations in weight restoration during inpatient treatment may be used to identify patients at risk for relapse. NCV can alert clinicians to initiate early relapse prevention interventions before discharge. Level of Evidence Level III, cohort study.}, } @article {pmid28709865, year = {2017}, author = {Wan, G and Tian, L and Yu, Y and Li, F and Wang, X and Li, C and Deng, S and Yu, X and Cai, X and Zuo, Z and Cao, F}, title = {Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.}, journal = {Biochemical and biophysical research communications}, volume = {491}, number = {1}, pages = {104-111}, doi = {10.1016/j.bbrc.2017.07.053}, pmid = {28709865}, issn = {1090-2104}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*mortality/pathology ; China/epidemiology ; Female ; Fucosyltransferases/*metabolism ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prevalence ; Prognosis ; Receptor, Notch1/*metabolism ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Up-Regulation ; }, abstract = {PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer.

MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter.

RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome.

CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.}, } @article {pmid28705686, year = {2017}, author = {Grimm, LJ and Ghate, SV and Hwang, ES and Soo, MS}, title = {Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.}, journal = {Academic radiology}, volume = {24}, number = {11}, pages = {1364-1371}, doi = {10.1016/j.acra.2017.05.017}, pmid = {28705686}, issn = {1878-4046}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Calcinosis/*diagnostic imaging ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology/surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; *Watchful Waiting ; }, abstract = {RATIONALE AND OBJECTIVES: The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS).

MATERIALS AND METHODS: We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded.

RESULTS: In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications.

CONCLUSIONS: Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance.}, } @article {pmid28702871, year = {2018}, author = {Hirayama, K and Kono, H and Nakata, Y and Akazawa, Y and Wakana, H and Fukushima, H and Fujii, H}, title = {Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer.}, journal = {Surgery today}, volume = {48}, number = {1}, pages = {110-118}, pmid = {28702871}, issn = {1436-2813}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/mortality/*pathology ; Disease-Free Survival ; Female ; Fibroblasts/*metabolism/*pathology ; *Gene Expression ; Humans ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/*genetics/*metabolism ; Middle Aged ; Pancreatic Neoplasms/*genetics/mortality/*pathology ; Prognosis ; Proportional Hazards Models ; Risk Factors ; }, abstract = {PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans.

METHODS: Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues.

RESULTS: PDPN was detected predominantly in stromal fibroblasts, stained with α-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram. There was no significant difference in clinicopathologic factors between patients with high vs. those with low PDPN expression. The high PDPN group showed significantly poorer disease-free and disease-specific survival rates than the low PDPN group. Among patients from the high PDPN group, those with lymph node metastases and those with a tumor larger than 20 cm in diameter had significantly poorer prognoses than similar patients from the low PDPN group. Multivariate Cox proportional hazards analysis indicated that a high expression of PDPN was an independent risk factor for disease-specific survival.

CONCLUSIONS: PDPN expression in cancer-related fibrotic tissues is associated with a poor prognosis, especially in patients with large tumors or lymph node metastases.}, } @article {pmid28700421, year = {2018}, author = {Xing, D and Jenson, EG and Zwick, CA and Rodriguez, FJ and Kurman, RJ}, title = {Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {37}, number = {1}, pages = {52-56}, doi = {10.1097/PGP.0000000000000389}, pmid = {28700421}, issn = {1538-7151}, mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Brain/pathology ; Brain Neoplasms/diagnostic imaging/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Cell Proliferation ; Cystadenocarcinoma, Serous/diagnostic imaging/pathology/*secondary/surgery ; Cystadenofibroma/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Encephalomalacia/diagnostic imaging/pathology/surgery ; Epithelial Cells/pathology ; Fallopian Tubes/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Ovarian Neoplasms/*pathology/surgery ; Salpingo-oophorectomy ; }, abstract = {A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A partial omentectomy showed no evidence of implants. In June 2016, the brain lesion was completely excised and diagnosed as an atypical proliferative (borderline) serous tumor. Immunohistochemical staining demonstrated that the tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that diagnosis. We present a brief review of possible mechanisms to account for this unusual presentation and speculate that the most likely one is exfoliation of fallopian tube epithelial cells into the peritoneal cavity, which then gain access to lymphatics resulting in cells implanting in the brain and subsequently progressing to an atypical proliferative (borderline) serous tumor.}, } @article {pmid28697523, year = {2018}, author = {Comino, MRS and Garcia, VR and López, MAF and Feddersen, B and Roselló, MLM and Sanftenberg, L and Schelling, J}, title = {[Assessment of IDC-Pal as a Diagnostic Tool for Family Physicians to Identify Patients with Complex Palliative Care Needs in Germany: a Pilot Study].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {80}, number = {10}, pages = {871-877}, doi = {10.1055/s-0043-104215}, pmid = {28697523}, issn = {1439-4421}, mesh = {Germany ; Humans ; *Needs Assessment ; *Palliative Care ; *Physicians, Family ; Pilot Projects ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Palliative medicine is an essential component of the health care system. Basic palliative care should be provided by primary care services (family physician and home nursing) with palliative-medical basic qualification. Often it is very difficult to identify patients that would profit from a specialized palliative care team. For the evaluation of the case complexity of a palliative patient, we present a Spanish diagnostic tool IDC-Pal, which tries to specify when, why and where a palliative patient should be referred. The aims of this study were the translation and cultural adaptation of the diagnostic tool for complexity in palliative care IDC-Pal to the German language, and the measurement of its feasibility and face validity.

METHODS: During the first phase, a forward-backward translation with linguistic and cultural adaptation of the tool IDC-Pal as well as the validation of its content by a review committee was performed. During the second phase, the preliminary version of the tool was tested by 38 family physicians that were asked for a qualitative assessment using a 10-points Likert scale (1 = "strongly disagree" and 10 = "totally agree"). Finally, a definitive version was developed.

RESULTS: The translation and adaptation were achieved without major problems. Both feasibility and apparent validity of the tool IDC-Pal were rated as high. The mean response in the Likert scale was 7.79, with a SD of 0.36. Participants strongly agreed on the apparent validity of the tool with a mean of 7.82 and a SD of 0.26 and on its feasibility with a mean of 7.79, and a SD of 0.39.

CONCLUSIONS: A conceptually, culturally and linguistically equivalent version of the original instrument IDC-Pal was obtained. German family physicians agreed on the usability of IDC-Pal as a tool for rating the case complexity of palliative patients. These results indicate that physicians in Bavaria and eventually in Germany could benefit of the full validation of IDC-Pal.}, } @article {pmid28695812, year = {2017}, author = {Wei, Y and Zhu, Q and Li, J and Jiang, Y}, title = {Clinical and Sonographic Features of Mammary Paget's Disease.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {39}, number = {3}, pages = {396-400}, doi = {10.3881/j.issn.1000-503X.2017.03.016}, pmid = {28695812}, issn = {1000-503X}, mesh = {Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Nipples/diagnostic imaging/pathology ; Paget's Disease, Mammary/*diagnostic imaging ; Retrospective Studies ; Ultrasonography ; }, abstract = {Objective To summarize the clinical and sonographic features of mammary Paget's disease (MPD). Methods Totally 34 female patients with pathologically confirmed MPD were retrospectively recruited. According to diagnosis,the clinical data and sonographic findings were reviewed and analyzed. Results Among these 34 patients,7 patients had single MPD; in the remaining 27 patients,16 were accompanied by invasive ductal carcinoma (IDC),7 by ductal carcinoma in situ (DCIS),3 by both IDC and DCIS,and 1 by other pathologic types of carcinoma. Twenty-four patients presented with typical clinical features of MPD,whereas 10 patients had no typical features of MPD. Among the 24 patients with typical clinical features,ultrasound examinations showed that 11 had echoic abnormality in nipple-areolar complex,14 had lesions of breast,and 14 had microcalcifications. Among the 10 patients without typical clinical features,ultrasound examinations revealed echoic abnormality in nipple-areolar complex in 3 cases,breast lesions in 9 cases,and microcalcifications in 6 cases. Among the 14 patients with echoic abnormality in nipple-areolar complex,all of them presented as rich blood flow in nipple detected by color Doppler ultrasonography. Conclusions The main clinical feature of MPD is abnormalities in nipple-areolar complex. Sonography can recognize the echoic abnormalities of nipple and lesions of breast. Sonographer should be careful of the nipple-areolar complex when mass is found in breast.}, } @article {pmid28693516, year = {2017}, author = {Sun, X and Zuo, K and Huang, D and Yu, B and Cheng, Y and Yang, W}, title = {Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.}, journal = {Diagnostic pathology}, volume = {12}, number = {1}, pages = {52}, pmid = {28693516}, issn = {1746-1596}, mesh = {Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Lobular/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Pancreatic Neoplasms/*secondary ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.

CASE PRESENTATION: We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.

CONCLUSIONS: To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.}, } @article {pmid28693189, year = {2017}, author = {Hong, OY and Noh, EM and Jang, HY and Lee, YR and Lee, BK and Jung, SH and Kim, JS and Youn, HJ}, title = {Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells via inactivation of the β-catenin signaling pathway.}, journal = {Oncology letters}, volume = {14}, number = {1}, pages = {441-446}, pmid = {28693189}, issn = {1792-1074}, abstract = {Epigallocatechin gallate (EGCG), a major constituent of green tea, has potential as a treatment for a variety of diseases, including cancer. EGCG induces apoptosis and inhibits tumorigenesis through multiple signaling pathways in breast cancer cells. β-catenin signaling modulators could be useful in the prevention and therapy of breast cancer. However, the precise anticancer effect of EGCG through the β-catenin signaling pathway in breast cancer is unclear. The present study investigated the association between β-catenin expression and clinicopathological factors of breast cancer patients, and the effect of EGCG on β-catenin expression in breast cancer cells. β-catenin expression was analyzed according to the clinicopathological factors of 74 patients with breast cancer. All patients were females diagnosed with invasive ductal carcinoma. Western blot analysis revealed that β-catenin was expressed at higher levels in breast cancer tissue than in normal tissue. β-catenin expression was associated with lymph node metastasis (P=0.04), tumor-node-metastasis stage (P=0.03) and estrogen receptor status (P<0.01). EGCG decreased MDA-MB-231 cell viability and significantly downregulated the expression of β-catenin, phosphorylated Akt and cyclin D1. Remarkably, additive effects of LY294002 and wortmannin, two phosphatidylinositol-3 kinase inhibitors, were observed. The present results suggest that EGCG inhibits the growth of MDA-MB-231 cells through the inactivation of the β-catenin signaling pathway. Based on these promising results, EGCG may be a potential treatment for triple negative breast cancer patients.}, } @article {pmid28693181, year = {2017}, author = {Olkhov-Mitsel, E and Siadat, F and Kron, K and Liu, L and Savio, AJ and Trachtenberg, J and Fleshner, N and van der Kwast, T and Bapat, B}, title = {Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.}, journal = {Oncology letters}, volume = {14}, number = {1}, pages = {390-396}, pmid = {28693181}, issn = {1792-1074}, abstract = {The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.}, } @article {pmid28690659, year = {2017}, author = {Tikku, G and Jain, M and Shukla, P}, title = {Chronic Myeloid Leukemia with a Complex Variant 'Ph' Translocation That Develops in Breast Carcinoma, Postchemotherapy: A Rare but Treatable Entity.}, journal = {Journal of breast cancer}, volume = {20}, number = {2}, pages = {208-211}, pmid = {28690659}, issn = {1738-6756}, abstract = {We report a case of chronic myeloid leukemia (CML) that developed after postoperative chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) for breast cancer. A 55-year-old woman was diagnosed with invasive ductal carcinoma which was treated with a modified radical mastectomy followed by six cycles of CAF chemotherapy. Nine years later, she developed CML and locoregional recurrence. Her breast recurrence showed strong estrogen receptor, weak progesterone receptor and strong human epidermal growth factor 2 (score 3+) expression. Her secondary CML in the chronic phase showed a complex variant translocation (CVT) involving chromosomes 9, 22, and 17. Considering that the HER2/neu gene is also located on chromosome 17, this secondary CML in chronic phase with CVT is indeed a rare occurrence. We discuss the associated genetic factors and the possible role of breast cancer chemo/radiotherapy in the development of such CML as well as its treatment and prognosis compared with de novo CML.}, } @article {pmid28690655, year = {2017}, author = {Xin, WR and Kwok, LL and Yong, WF}, title = {Screening Uptake Differences Are Not Implicated in Poorer Breast Cancer Outcomes among Singaporean Malay Women.}, journal = {Journal of breast cancer}, volume = {20}, number = {2}, pages = {183-191}, pmid = {28690655}, issn = {1738-6756}, abstract = {PURPOSE: This study was undertaken to examine the impact of screening and race on breast cancer outcomes in Singapore.

METHODS: An institutional database was reviewed, and invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) data were analyzed separately. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were assessed.

RESULTS: The study included 6,180 IDC and 1,031 DCIS patients. The median follow-up time was 4.1 years. Among IDC patients, Malay women were the youngest when first diagnosed, and were more likely to present with advanced stage disease. Malay women also had the highest proportion of T3 and T4 tumors at 14.2%, compared with Chinese women at 8.7% and Indian women at 9.6% (p<0.001). Malay women had a higher incidence of node-positive disease at 58.3% compared with Chinese women at 46.4% and Indian women at 54.9% (p<0.001). Malay subjects also had higher-grade tumors; 61.8% had grade 3 tumors compared with 45.8% of Chinese women and 52% of Indian women (p<0.001). Furthermore, tumors in Malay subjects were less endocrine-sensitive and more human epidermal growth factor receptor 2 enriched. Malay women had the lowest 5- and 10-year OS, DFS, and CSS rates (p<0.001). After separating clinically and screen-detected tumors, multivariate analysis showed that race was still significant for outcomes. For screen-detected tumors, the OS hazard ratio (HR) for Malay women compared to Chinese women was 5.78 (95% confidence interval [CI], 2.64-12.64), the DFS HR was 2.18 (95% CI, 1.19-3.99), and the CSS HR was 5.93 (95% CI, 2.15-16.39). For DCIS, there were no statistically significant differences in the tumor size, grade, histology subtypes, or hormone sensitivity.

CONCLUSION: Malay race is a poor prognostic factor in both clinically and screen-detected IDC. Special attention should be given to the detection and follow-up of breast cancer in this group.}, } @article {pmid28689011, year = {2018}, author = {Co, M and Tse, GM and Chen, C and Wei, J and Kwong, A}, title = {Coexistence of Ductal Carcinoma Within Mammary Phyllodes Tumor: A Review of 557 Cases From a 20-year Region-wide Database in Hong Kong and Southern China.}, journal = {Clinical breast cancer}, volume = {18}, number = {3}, pages = {e421-e425}, doi = {10.1016/j.clbc.2017.06.001}, pmid = {28689011}, issn = {1938-0666}, mesh = {Adult ; Breast Neoplasms/diagnosis/*epidemiology ; Carcinoma, Ductal, Breast/diagnosis/*epidemiology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*epidemiology ; China/epidemiology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hong Kong/epidemiology ; Humans ; Incidence ; Middle Aged ; Neoplasms, Multiple Primary ; Phyllodes Tumor/diagnosis/*epidemiology ; Prognosis ; Prospective Studies ; Retrospective Studies ; }, abstract = {INTRODUCTION: Phyllodes tumor (PT) is an uncommon fibroepithelial tumor of the breast showing predominately proliferation of the stromal component. The presence of ductal carcinoma in situ (DCIS) or invasive ductal carcinoma is rare, with only a few cases reported in the literature.

METHODS: A retrospective review of a prospectively maintained database was performed. Patients who were treated for PT in 5 hospitals in Hong Kong and Shenzhen, China over a period of 20 years (1997-2016) were evaluated. All pathology slides were reported by specialist pathologists. Patients with coexisting ductal carcinoma were identified.

RESULTS: A total of 557 patients were included in this cohort; 363 (65.2%) patients had benign PT, 130 (23.3%) had borderline PT, and 64 (11.5%) had malignant PT. There were 6 (1.1%) patients with coexisting ductal carcinoma in the PT; 5 were DCIS and 1 was invasive ductal carcinoma. The median age was 46.5 years (range, 25-54 years). Ductal carcinoma occurred more frequently in malignant PT than in benign or borderline PT (4.7% vs. 0.6%; P = .02). However, malignant PT was not associated with higher DCIS grade (P = .1). All patients underwent surgery with clear resection margins. After a median follow-up interval of 70 months (range, 2-101 months), all patients remained disease- and recurrence-free.

CONCLUSION: We report 6 additional uncommon cases of ductal carcinoma complicating PT. The presence of ductal carcinoma was not adverse prognosticator as these are usually incidental and situated within the harboring PT.}, } @article {pmid28686225, year = {2017}, author = {Pucci-Minafra, I and Di Cara, G and Musso, R and Cancemi, P and Albanese, NN and Roz, E and Minafra, S}, title = {Retrospective Proteomic Screening of 100 Breast Cancer Tissues.}, journal = {Proteomes}, volume = {5}, number = {3}, pages = {}, pmid = {28686225}, issn = {2227-7382}, abstract = {The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The specimens were selected from patients with invasive ductal carcinoma of the breast, the most frequent and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers potentially useful for clinical applications. The proteomic screening; by 2D-IPG and mass spectrometry; allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients; and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is reasonably supported by concurrent events: the inhibition of apoptosis and stimulation of cellular proliferation, and the increased expression of glycolytic enzymes with multiple functions. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. We suggest that this approach on large-scale 2D-IPG proteomics of breast cancer is currently a valid tool that offers the opportunity to evaluate on the same assay the presence and recurrence of individual proteins, their isoforms and short forms, to be proposed as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.}, } @article {pmid28685793, year = {2016}, author = {El Amine, O and Ouni, R and Adouni, O and Goucha, A and Ben Hassouna, J and Rahal, K and El May, A and Gamoudi, A}, title = {Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.}, journal = {La Tunisie medicale}, volume = {94}, number = {8-9}, pages = {587-593}, pmid = {28685793}, issn = {0041-4131}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; *Cell Proliferation ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; *Mitotic Index ; Prognosis ; }, abstract = {BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle.

AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker.

METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method.

RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score.

CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.}, } @article {pmid28681371, year = {2017}, author = {Kumaki, N and Okamatsu, C and Tokuda, Y and Nakamura, N}, title = {Breast Cancer in Patients of Rheumatoid Arthritis with Methotrexate Therapy Mimicking Histopathological Changes after Neoadjuvant Chemotherapy.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {42}, number = {2}, pages = {104-108}, pmid = {28681371}, issn = {2185-2243}, mesh = {Aged ; Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy ; Breast/*pathology ; Breast Neoplasms/complications/*pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology/*therapy ; *Chemotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Methotrexate/*therapeutic use ; Middle Aged ; *Neoadjuvant Therapy ; }, abstract = {Two breast cancer patients with a history of treatment for long-term rheumatoid arthritis (RA) had histological findings similar to histological changes seen in resected mammary gland specimens following neoadjuvant chemotherapy (NAC). The first patient was a 64-year-old woman who visited our hospital after feeling a lump in her left breast. The second patient was a 68-year-old woman who visited our hospital for an indentation in her left nipple. They were diagnosed with breast cancer following detailed examinations and underwent mastectomy. Both patients had a history of RA and were being treated with Methotrexate. The histological diagnoses of these patients were invasive ductal carcinoma, but frequent dispersal of cancer cell nests, stromal fibrosis, elastosis, edema and inflammatory cell infiltration were seen. Fibrosis was also found in the dissected lymph node. These histological findings were extremely similar to changes that occur in the mammary gland tissue after NAC; however, these patients had not undergone NAC. Methotrexate, which was being administered as an anti-rheumatic drug to the two patients, might have played a role similar to that of metronomic chemotherapy, which involves the continuous use of low-dose anti-cancer drugs, resulting in histological changes similar to those seen after NAC.}, } @article {pmid28678576, year = {2017}, author = {Jena, A and Taneja, S and Singh, A and Negi, P and Sarin, R and Das, PK and Singhal, M}, title = {Reliability of [18]F-FDG PET Metabolic Parameters Derived Using Simultaneous PET/MRI and Correlation With Prognostic Factors of Invasive Ductal Carcinoma: A Feasibility Study.}, journal = {AJR. American journal of roentgenology}, volume = {209}, number = {3}, pages = {662-670}, doi = {10.2214/AJR.16.17766}, pmid = {28678576}, issn = {1546-3141}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Feasibility Studies ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Multimodal Imaging/*methods ; Neoplasm Grading ; Neoplasm Invasiveness ; Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals/*pharmacokinetics ; Reproducibility of Results ; Whole Body Imaging ; }, abstract = {OBJECTIVE: The objective of our study was to correlate semiquantitative PET parameters-standardized uptake value (SUV) and total lesion glycolysis (TLG)-derived in simultaneous PET/MRI using MRI-based attenuation correction with clinical and histopathologic prognostic factors in patients with breast cancer.

MATERIALS AND METHODS: Eighty-two invasive ductal carcinomas in 69 women were included in the study. All the subjects underwent whole-body (WB) PET/MRI (supine WB mode) and dedicated PET/MRI of the breast (prone breast imaging mode) for staging on a simultaneous PET/MRI system. The SUV and TLG values were calculated from [18]F-FDG PET data using MRI-based attenuation correction (2-point Dixon sequence for tissue segmentation). Relationships between SUV and TLG values and clinical and histopathologic parameters (i.e., tumor size, tumor grade, Ki-67 status, and hormonal receptor expression status) were evaluated using Spearman correlation coefficient analysis.

RESULTS: A significant correlation was observed between mean SUV (SUVmean) and maximum SUV (SUVmax) values derived with WB PET and regional PET of the breasts performed simultaneously with MRI (r = 0.88 and 0.89, respectively). A significant difference (p < 0.05) was observed in SUVmean, SUVmax, and TLG values between the grades and molecular subtypes of breast cancer. High SUVmean, SUVmax, and TLG values were found to correlate with larger tumor size (p < 0.01), higher proliferation index (p < 0.05), higher grade (p < 0.01), and triple-negative hormonal receptor status (p < 0.01, p < 0.05).

CONCLUSION: Semiquantitative FDG parameters derived with MRI-based attenuation correction in simultaneous PET/MRI are reliable and correlate with clinicopathologic features such as grade as well as subtype and thus could be used in the prognostication of breast cancer.}, } @article {pmid28671041, year = {2017}, author = {Liu, B and Xiong, J and Liu, G and Wu, J and Wen, L and Zhang, Q and Zhang, C}, title = {High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {7}, pages = {1010428317710908}, doi = {10.1177/1010428317710908}, pmid = {28671041}, issn = {1423-0380}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; *Prognosis ; rac1 GTP-Binding Protein/*biosynthesis/genetics ; }, abstract = {The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (rs = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a therapeutic target for breast cancer.}, } @article {pmid28669452, year = {2017}, author = {Fayaz, S and Demian, GA and Eissa, HE and Amanguno, H and Abuzalouf, S}, title = {Metaplastic breast carcinoma: Analysis of 31 cases from a single institute.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {29}, number = {3}, pages = {141-145}, doi = {10.1016/j.jnci.2017.05.002}, pmid = {28669452}, issn = {2589-0409}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/mortality/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Treatment Outcome ; }, abstract = {PURPOSE: Metaplastic carcinoma of the breast (MBC) accounts for less than 1% of all mammary tumors. This study aimed at revision of the clinico-pathological features, treatment strategy and outcome for MBC patients presented to the Kuwait Cancer Control Center to define the clinical behavior and prognostic factors of these neoplasms in our population.

PATIENT AND METHODS: Thirty-one patients were retrieved from our surgical pathology registry between January 2005 and December 2014. Medical records were revised regarding the clinico-pathological features and treatment outcome.

RESULTS: MBC represented 1% of our breast cancer patients. The median age was 50years (32-70years). Two patients presented with metastatic disease. Mastectomy was done for 24 patients and 7 had conservative surgery. The median tumor size at the time of surgery was 5.5cm (1.5-12cm). Axillary nodes were negative in 21 patients (N0), 5 patients were N1, 4 patients were N2 and one Nx. Three histological subtypes were presented: carcinosarcoma (7 cases), squamous cell carcinoma/IDC with squamous differentiation (15 cases), high grade IDC with metaplastic differentiation (9 cases). Immunohistochemically, 26 were negative hormone receptors and all were negative for Her2/neu overexpression. Chemotherapy was used in 28 patients, and adjuvant radiotherapy in 24 patients. The median follow-up was 47months (7-126months), six patients lost follow-up. The 5-year OS was 69% and 5-year PFS was 50%.

CONCLUSION: MBC is a rare entity among breast carcinoma in Kuwait. Most of the cases present with poor prognostic indicators and often show lack of expression of ER, PR and Her2/neu.}, } @article {pmid28665960, year = {2017}, author = {Ellinas, C and Allan, N and Johansson, A}, title = {Dynamics of organizational culture: Individual beliefs vs. social conformity.}, journal = {PloS one}, volume = {12}, number = {6}, pages = {e0180193}, pmid = {28665960}, issn = {1932-6203}, mesh = {Humans ; *Organizational Culture ; *Social Conformity ; }, abstract = {The complex nature of organizational culture challenges our ability to infer its underlying dynamics from observational studies. Recent computational studies have adopted a distinctly different view, where plausible mechanisms are proposed to describe a wide range of social phenomena, including the onset and evolution of organizational culture. In this spirit, this work introduces an empirically-grounded, agent-based model which relaxes a set of assumptions that describes past work-(a) omittance of an individual's strive for achieving cognitive coherence; (b) limited integration of important contextual factors-by utilizing networks of beliefs and incorporating social rank into the dynamics. As a result, we illustrate that: (i) an organization may appear to be increasingly coherent in terms of its organizational culture, yet be composed of individuals with reduced levels of coherence; (ii) the components of social conformity-peer-pressure and social rank-are influential at different aggregation levels.}, } @article {pmid28661760, year = {2017}, author = {Curigliano, G and Criscitiello, C}, title = {Maximizing the Clinical Benefit of Anthracyclines in Addition to Taxanes in the Adjuvant Treatment of Early Breast Cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {23}, pages = {2600-2603}, doi = {10.1200/JCO.2017.72.5960}, pmid = {28661760}, issn = {1527-7755}, mesh = {Anthracyclines/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration & dosage ; Carcinoma, Ductal, Breast/secondary/*therapy ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; *Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Radiotherapy, Adjuvant ; Taxoids/administration & dosage ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m[2]). Our multidisciplinary tumor board recommended adjuvant chemotherapy, postsurgical radiation therapy, and endocrine therapy.}, } @article {pmid28658335, year = {2017}, author = {Aquino, RGF and Vasques, PHD and Cavalcante, DIM and Oliveira, ALS and Oliveira, BMK and Pinheiro, LGP}, title = {Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {44}, number = {2}, pages = {163-170}, doi = {10.1590/0100-69912017002010}, pmid = {28658335}, issn = {1809-4546}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology/*secondary ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVE: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma.

METHODS: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases.

RESULTS: the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001).

CONCLUSION: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.}, } @article {pmid28652380, year = {2017}, author = {Gil Del Alcazar, CR and Huh, SJ and Ekram, MB and Trinh, A and Liu, LL and Beca, F and Zi, X and Kwak, M and Bergholtz, H and Su, Y and Ding, L and Russnes, HG and Richardson, AL and Babski, K and Min Hui Kim, E and McDonnell, CH and Wagner, J and Rowberry, R and Freeman, GJ and Dillon, D and Sorlie, T and Coussens, LM and Garber, JE and Fan, R and Bobolis, K and Allred, DC and Jeong, J and Park, SY and Michor, F and Polyak, K}, title = {Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.}, journal = {Cancer discovery}, volume = {7}, number = {10}, pages = {1098-1115}, pmid = {28652380}, issn = {2159-8290}, support = {F32 CA156991/CA/NCI NIH HHS/United States ; R35 CA197623/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; }, mesh = {B7-H1 Antigen/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*immunology ; CD3 Complex/genetics ; Carcinoma, Ductal, Breast/genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*immunology ; Disease Progression ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Leukocyte Common Antigens/genetics ; Receptor, ErbB-2/genetics ; T-Lymphocytes/*immunology ; Tumor Microenvironment ; }, abstract = {To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45[+]CD3[+] T cells demonstrated a decrease in CD8[+] signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB[+]CD8[+] T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2[+] breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.}, } @article {pmid28647915, year = {2017}, author = {Kizy, S and Huang, JL and Marmor, S and Tuttle, TM and Hui, JYC}, title = {Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {165}, number = {3}, pages = {757-763}, doi = {10.1007/s10549-017-4355-9}, pmid = {28647915}, issn = {1573-7217}, mesh = {Adolescent ; Adult ; Aged ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Lobular/*genetics/*mortality/pathology ; Female ; *Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) of the breast has unique clinicopathologic characteristics, compared to invasive ductal carcinoma. The role of the 21-gene Recurrence Score (RS) has not been clearly defined for ILC. We sought to determine the prognostic value of RS and the impact of adjuvant chemotherapy on long-term survival in patients with ILC.

METHODS: Utilizing the Surveillance, Epidemiology and End Results database from 2004 to 2013, we identified records of women aged 18-74 years, diagnosed with estrogen receptor (ER)-positive ILC (stage I to III) with RS available. We categorized patients into risk groups based on the traditional RS cutoffs and into those of the Trial Assigning Individualized Options for Treatment (TAILORx). Five-year breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and Cox proportional hazards models.

RESULTS: Of the 7316 women included, 21% were in the low-risk; 71%, intermediate-risk; and 8%, high-risk groups as per TAILORx RS cutoffs. The 5-year BCSS was 99% in the low-risk, 99% in the intermediate-risk, and 96% in the high-risk groups. A high-risk RS as per TAILORx cutoff was independently associated with increased mortality (hazard ratio [HR] of death 2.37, 95% confidence interval [CI] 1.14-4.95) when compared to a low-risk RS. In both the high-risk and intermediate-risk groups, adjuvant chemotherapy was not significantly associated with the HR of death (high-risk, HR 1.14, 95% CI 0.55-2.38; intermediate-risk, HR 1.08, 95% CI 0.62-1.87).

CONCLUSION: For patients with ER-positive ILC, 8% were in the high-risk and 72% were in the intermediate-risk groups as per the TAILORx RS cutoffs. In the high-risk group, the RS predicted a lower 5-year BCSS. Adjuvant chemotherapy did not seem to confer a survival benefit for either the intermediate- or the high-risk cohorts.}, } @article {pmid28646729, year = {2017}, author = {Cyniak-Cieciura, M and Staniaszek, K and Popiel, A and Pragłowska, E and Zawadzki, B}, title = {The structure of PTSD symptoms according to DSM-5 and IDC-11 proposal: A multi-sample analysis.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {44}, number = {}, pages = {179-186}, doi = {10.1016/j.eurpsy.2017.02.491}, pmid = {28646729}, issn = {1778-3585}, mesh = {Borderline Personality Disorder/*classification/*diagnosis/epidemiology ; Comorbidity ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Stress Disorders, Post-Traumatic/*classification/*diagnosis/epidemiology ; }, abstract = {Posttraumatic stress disorder (PTSD) symptoms structure is a subject of ongoing debate since its inclusion in DSM-III classification in 1980. Different research on PTSD symptoms structure proved the better fit of four-factor and five-factor models comparing to the one proposed by DSM-IV. With the publication of DSM-5 classification, which introduced significant changes to PTSD diagnosis, the question arises about the adequacy of the proposed criteria to the real structure of disorder symptoms. Recent analyses suggest that seven-factor hybrid model is the best reflection of symptoms structure proposed to date. At the same time, some researchers and ICD-11 classification postulate a simplification of PTSD diagnosis restricting it to only three core criteria and adding additional diagnostic unit of complex-PTSD. This research aimed at checking symptoms' structure according to well-known and supported four-, five-, six- and seven-factor models based on DSM-5 symptoms and the conceptualization proposed by the ICD-11 as well as examining the relation between PTSD symptoms categories with borderline personality disorder. Four different trauma populations were examined with self-reported Posttraumatic Diagnostic Scale for DSM-5 (PDS-5) measure. The results suggest that six- and seven-factor hybrid model as well as three-factor ICD-11 concept fits the data better than other models. The core PTSD symptoms were less related to borderline personality disorder than other, broader, symptoms categories only in one sample. Combination of ICD-11 simplified PTSD diagnosis with the more complex approach (e.g. basing on a seven-factor model) may be an attractive proposal for both scientists and practitioners, however does not necessarily lower its comorbidity with borderline personality disorder.}, } @article {pmid28645279, year = {2017}, author = {Murphy, A and Biringanine, M and Roberts, B and Stringer, B and Perel, P and Jobanputra, K}, title = {Diabetes care in a complex humanitarian emergency setting: a qualitative evaluation.}, journal = {BMC health services research}, volume = {17}, number = {1}, pages = {431}, pmid = {28645279}, issn = {1472-6963}, mesh = {Adolescent ; Adult ; Aged ; *Altruism ; Ambulatory Care/methods ; Delivery of Health Care/standards ; Democratic Republic of the Congo ; Diabetes Mellitus, Type 1/psychology/*therapy ; Diabetes Mellitus, Type 2/psychology/*therapy ; Diet, Healthy/psychology ; Emergency Treatment/methods ; Family Relations ; Female ; Focus Groups ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Medication Adherence/statistics & numerical data ; Middle Aged ; Patient Acceptance of Health Care/statistics & numerical data ; Patient Compliance/psychology/statistics & numerical data ; Program Evaluation ; Qualitative Research ; Travel ; Young Adult ; }, abstract = {BACKGROUND: Evidence is urgently needed from complex emergency settings to support efforts to respond to the increasing burden of diabetes mellitus (DM). We conducted a qualitative study of a new model of DM health care (Integrated Diabetic Clinic within an Outpatient Department [IDC-OPD]) implemented by Médecins Sans Frontières (MSF) in Mweso Hospital in eastern Democratic Republic of Congo (DRC). We aimed to explore patient and provider perspectives on the model in order to identify factors that may support or impede it.

METHODS: We used focus group discussions (FGDs; two discussions, each with eight participants) and individual semi-structured qualitative interviews (seven patients and 10 staff) to explore experience of and perspectives on the IDC-OPD. Participants were recruited purposively to represent a range of DM disease severity and staff functions respectively, and to ensure the age and gender distribution was representative of the population of DM patients registered in the clinic. Data were coded in NVivo10© and analysed using an inductive thematic approach.

RESULTS: There appears to be little awareness surrounding DM in patient communities, resulting in delays presenting to hospital. Patients describe their first reactions to symptoms as fear and confusion, often assuming symptoms are of another disease (e.g. HIV/AIDS). They often express disbelief that they could have DM (e.g. stating DM is a 'rich man's disease') and lack acceptance that there is no cure. Patients experienced difficulty travelling to appointments, exacerbated by flare-ups in the conflict. Providing psycho-social and sensitisation activities in a group setting appears to offer an opportunity for patients to support each other in their effort to adhere to drug treatment and follow-up appointments. All patients reported great difficulty in adhering to the recommended diet, which was viewed as unaffordable and unavailable, and fear that this would be the biggest obstacle to maintaining their drug treatment (as treatment must be taken with food).

CONCLUSION: Our findings emphasize the importance of community awareness of DM and the value of treatment support, including psychosocial and educational support to DM patients and their families, and culturally sensitive, low-cost dietary advice, to ensuring the adoption and maintenance of DM treatment.}, } @article {pmid28644994, year = {2017}, author = {Bouzaiene, H and Triki, A and Ghalleb, M and Chemlali, M and Benzarti, Z and Ben Hassouna, J and Gammoudi, A and Rahal, K}, title = {Is the systematic circumferential tumor cavity shaving a representative sample for the remaining mammary gland? About 75 cases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {35}, number = {}, pages = {27-31}, doi = {10.1016/j.breast.2017.06.008}, pmid = {28644994}, issn = {1532-3080}, mesh = {Adult ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm, Residual/pathology/*surgery ; Organ Sparing Treatments/*methods ; }, abstract = {INTRODUCTION: The conservative surgery is more and more indicated for breast cancer. However, we still fear local recurrence which is mostly due to residual tumors?. Several techniques have been used to minimize theses residual tumors; one of them is the systematic circumferential tumor cavity shaving (SCTCS).

METHODS: We sampled 75 female patients who had conservative surgery with positive shaved margins in the anatomopathology examination and to whom a complementary treatment with mastectomy have been decided.

RESULTS: The median age was 48 years old. The median tumor size was 23 mm. In the histological examination of the tumors, 93% were invasive ductal carcinoma associated in 50% of the cases to the presence of ductal carcinoma in situ (DCIS) where all the lumpectomies had clear margin. For the SCTCS, 62,2% were DCIS and in 17,6% of the cases were invasive ductal carcinoma. A complementary treatment with mastectomy was indicated to all the patients. A residual tumor was detected in the remaining mammary gland in 47,7% of the cases out of which 50% were DCIS. Local recurrence happened in three patients (4,6%) after a median of follow up of 36 months. The overall survival and the disease free survival at five years were respectively 83,6% and 75,5%.

CONCLUSION: Standardized lumpectomy cavity shaving provides a backup to lumpectomy margins in conservative breast surgery but it can also be used as a sample for the remaining breast, helping to detect the residual tumor, and decreasing the rates of local recurrence after BCT.}, } @article {pmid28640531, year = {2018}, author = {Thakur, SB and Durando, M and Milans, S and Cho, GY and Gennaro, L and Sutton, EJ and Giri, D and Morris, EA}, title = {Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {47}, number = {2}, pages = {401-409}, pmid = {28640531}, issn = {1522-2586}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Lymph Nodes ; Middle Aged ; Neoplasm Recurrence, Local/*diagnostic imaging ; Receptor, ErbB-2 ; }, abstract = {PURPOSE: To measure the apparent diffusion coefficient (ADC) values in estrogen receptor-positive (ER+) and axillary lymph node-negative (LN-) invasive breast cancer and investigate the correlation of ADC with Oncotype Dx test recurrence scores (ODxRS).

MATERIALS AND METHODS: This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant single-site retrospective study. Patients underwent preoperative 3.0T MRI scans with additional diffusion-weighted imaging sequential scans (b = 0, 600 and b = 0, 1000 s/mm[2]) from January 2011 to 2013. The study population included 31 ER+/LN- invasive breast cancers, which underwent ODxRS genomic testing. ADC600 and ADC1000 parametric maps were generated, and ADC values were calculated from a user-drawn region of interest. ODxRS predicts 10-year recurrence risk in individual patients: low (RS <18), intermediate (RS: 18-30), or high (RS >30). All breast lesions, including subgroups of invasive ductal carcinoma (IDC) lesions and mass-only lesions were dichotomized by RS scores, low-risk versus intermediate/high-risk, and statistical analysis was performed using Mann-Whitney's test (statistical significance at P < 0.05) and receiver operating characteristic (ROC) curves. Multivariate analysis was also performed.

RESULTS: Invasive breast cancers, when scored as low-risk by ODxRS, had significantly higher ADC values compared with intermediate/high-risk lesions for both ADC600 (P = 0.007) and ADC1000 (P = 0.008) mean values. This was true both when analyzing only mass-lesions (P = 0.03 and 0.01) or only IDCs (P = 0.001 and 0.009).

CONCLUSION: Preliminary findings suggest that lesion ADC values correlate with recurrence risk likelihood stratified using ODxRS. Hence, ADC is a potential surrogate biomarker for tumor aggressiveness.

LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:401-409.}, } @article {pmid28638056, year = {2017}, author = {Li, Z and Du, B and Han, C and Xu, H}, title = {Trap Modulated Charge Carrier Transport in Polyethylene/Graphene Nanocomposites.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {4015}, pmid = {28638056}, issn = {2045-2322}, abstract = {The role of trap characteristics in modulating charge transport properties is attracting much attentions in electrical and electronic engineering, which has an important effect on the electrical properties of dielectrics. This paper focuses on the electrical properties of Low-density Polyethylene (LDPE)/graphene nanocomposites (NCs), as well as the corresponding trap level characteristics. The dc conductivity, breakdown strength and space charge behaviors of NCs with the filler content of 0 wt%, 0.005 wt%, 0.01 wt%, 0.1 wt% and 0.5 wt% are studied, and their trap level distributions are characterized by isothermal discharge current (IDC) tests. The experimental results show that the 0.005 wt% LDPE/graphene NCs have a lower dc conductivity, a higher breakdown strength and a much smaller amount of space charge accumulation than the neat LDPE. It is indicated that the graphene addition with a filler content of 0.005 wt% introduces large quantities of deep carrier traps that reduce charge carrier mobility and result in the homocharge accumulation near the electrodes. The deep trap modulated charge carrier transport attributes to reduce the dc conductivity, suppress the injection of space charges into polymer bulks and enhance the breakdown strength, which is of great significance in improving electrical properties of polymer dielectrics.}, } @article {pmid28633434, year = {2017}, author = {Singh, DK and Gholamalamdari, O and Jadaliha, M and Ling Li, X and Lin, YC and Zhang, Y and Guang, S and Hashemikhabir, S and Tiwari, S and Zhu, YJ and Khan, A and Thomas, A and Chakraborty, A and Macias, V and Balla, AK and Bhargava, R and Janga, SC and Ma, J and Prasanth, SG and Lal, A and Prasanth, KV}, title = {PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.}, journal = {Carcinogenesis}, volume = {38}, number = {10}, pages = {966-975}, pmid = {28633434}, issn = {1460-2180}, support = {R01 GM088252/GM/NIGMS NIH HHS/United States ; R01 GM099669/GM/NIGMS NIH HHS/United States ; R01 GM123314/GM/NIGMS NIH HHS/United States ; R01 HG007352/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Breast Neoplasms/*genetics/mortality/*pathology ; Cell Cycle/*genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chromatin/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oncogenes ; Promoter Regions, Genetic ; RNA Polymerase II/genetics/metabolism ; Tissue Array Analysis ; Transcription Factors/*genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.}, } @article {pmid28631956, year = {2017}, author = {Siciliano, M and Santangelo, G and Trojsi, F and Di Somma, C and Patrone, M and Femiano, C and Monsurrò, MR and Trojano, L and Tedeschi, G}, title = {Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS).}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {18}, number = {5-6}, pages = {367-377}, doi = {10.1080/21678421.2017.1285316}, pmid = {28631956}, issn = {2167-9223}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Amyotrophic Lateral Sclerosis/*psychology/*therapy ; Caregivers/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Quality of Life/psychology ; Stress, Psychological/*psychology/*therapy ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) causes distress in caregivers. The present study aims to examine the association between coping strategies and psychological distress in caregivers of ALS patients.

METHODS: Coping strategies were assessed in 96 ALS informal caregivers by means of the Coping Inventory for Stressful Situations. Data about caregivers' demographic characteristics, levels of burden, depression and anxiety (psychological distress) were also gathered by standardised questionnaires. Patients' clinical, cognitive and behavioural disturbances were evaluated by ALS specific assessment tools.

RESULTS: Sequential logistic regression analysis showed that emotion-oriented coping strategy was significantly associated with high levels of depressive (p < 0.01) and anxiety (p < 0.05) symptoms and high levels of burden (p < 0.05), after controlling for all other variables. Moreover, a significant relationship of patients' functional dependence levels with burden experienced by caregivers was observed. No relationships were detected between task-oriented and avoidance-oriented coping strategies and caregivers' levels of psychological distress.

CONCLUSIONS: The present study supported the mediating effects of coping strategies on intensity of burden, depression and anxiety experienced by ALS caregivers. These findings suggest that interventions aimed at reducing utilisation of maladaptive coping strategies may improve well-being in ALS caregivers, and, possibly, management of symptoms in ALS patients.}, } @article {pmid28629734, year = {2017}, author = {Zouine, S and Orfi, Z and Kojok, K and Benayad, S and Zaid, Y and Marnissi, F and Habti, N}, title = {Immunohistochemical and genetic exploration of incompatible A blood group antigen expression in invasive micropapillary breast carcinoma: A case report.}, journal = {Current research in translational medicine}, volume = {65}, number = {2}, pages = {71-76}, doi = {10.1016/j.retram.2017.05.002}, pmid = {28629734}, issn = {2452-3186}, abstract = {INTRODUCTION: Invasive Micropapillary Carcinoma (IMPC) of the breast is a relatively rare subtype of invasive ductal carcinoma and represents the most inherently aggressive form. Expression of incompatible blood group A antigen in cancer of type O patients has been reported in several types of cancer, however, the biosynthetic mechanism and the genetic basis remain unclear until today. The aim of the present case report study was to evaluate the expression of incompatible blood group A antigen and to identify the genetic basis of this expression in IMPC of the breast.

MATERIAL AND METHODS: One patient blood group O with Invasive Micropapillary Carcinoma was screened at Pathology Department of University Hospital CHU Ibn Rochd, Casablanca. ABH antigens expression was assessed by immunohistochemistry. ABO genotyping was performed by allele specific primers PCR-ASP and Exon 6 of ABO gene was sequenced with Sanger method.

RESULTS: H antigen was expressed in endothelial and epithelial cells of normal tissue. However, H antigen expression was lost in both invasive micropapillary carcinomas. A antigen was expressed in IMPC with approximately 80% of positive cells. Tumor DNA was genotyped as heterozygous A/O. In normal DNA, we identified a single frameshift deletion c.320delA p.(Glu107Glyfs[*]12), which is removed from tumor DNA.

CONCLUSION: Our findings suggest that incompatible A antigen expression in IMPC is due to glycosyltransferase A encoded by an A allele which is derived from O allele with a deletion at the position 320.}, } @article {pmid28628772, year = {2017}, author = {Carbognin, L and Sperduti, I and Fabi, A and Dieci, MV and Kadrija, D and Griguolo, G and Pilotto, S and Guarneri, V and Zampiva, I and Brunelli, M and Orvieto, E and Nortilli, R and Fiorio, E and Parolin, V and Manfrin, E and Caliò, A and Nisticò, C and Pellini, F and Scarpa, A and Pollini, GP and Conte, P and Tortora, G and Bria, E}, title = {Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.}, journal = {Breast (Edinburgh, Scotland)}, volume = {35}, number = {}, pages = {21-26}, doi = {10.1016/j.breast.2017.06.005}, pmid = {28628772}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Lobular/*immunology/*pathology ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {INTRODUCTION: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC).

METHODS: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.

RESULTS: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.

CONCLUSIONS: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.}, } @article {pmid28625953, year = {2017}, author = {Zhai, Y and Chai, L and Chen, J}, title = {The relationship between the expressions of tumor associated fibroblasts Cav-1 and MCT4 and the prognosis of papillary carcinoma of breast.}, journal = {Pakistan journal of pharmaceutical sciences}, volume = {30}, number = {1 Suppl}, pages = {263-272}, pmid = {28625953}, issn = {1011-601X}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/*pathology ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Carcinogenesis/metabolism/pathology ; Carcinoma, Papillary/*metabolism/*pathology ; Caveolin 1/*metabolism ; Female ; Humans ; Middle Aged ; Monocarboxylic Acid Transporters/*metabolism ; Muscle Proteins/*metabolism ; Prognosis ; Tumor Microenvironment/physiology ; Up-Regulation/physiology ; }, abstract = {The aim of this study was to evaluate the expression levels of Cav-1 and MCT4 in the tumor stroma CAFs. Immunohistochemical method was used to detect the expression of Cav-1 and MCT4 in 86 cases of IMPC, with 105 cases of non-specific invasive ductal carcinoma (IDC-NOS) as control. Their differential expression in different histological types were compared and relationship between the expression of Cav-1 and IMPC in the MCT4 and the main pathological features such as age, tumor size and histological grades were analyzed. The study confirmed that the loss expression of Cav-1 on CAFs and the up-regulation of MCT4 may be the possible mechanisms of CAFs in tumorigenesis, which may be one of the molecular mechanisms leading to the poor prognosis of IMPC. The expression of CAFs related proteins in tumor microenvironment suggested that CAFs could be used as the target of tumor therapy and provide new evidence for the treatment of breast cancer.}, } @article {pmid28625415, year = {2018}, author = {de Zárraga Mata, C and Thomas Salom, G and Vilella Martorell, A and Salvà Ramonell, F and Maura Oliver, ÁL and Dolz Abadía, C}, title = {Gastric metastatic extension of invasive ductal carcinoma of the breast with atypical endoscopic presentation.}, journal = {Gastroenterologia y hepatologia}, volume = {41}, number = {5}, pages = {304-305}, doi = {10.1016/j.gastrohep.2017.04.006}, pmid = {28625415}, issn = {0210-5705}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/therapy ; Chemoradiotherapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; *Gastroscopy ; Humans ; Image-Guided Biopsy ; Incidental Findings ; Lymphatic Metastasis ; Mastectomy, Segmental ; Stomach Neoplasms/*diagnostic imaging/therapy ; }, } @article {pmid28623240, year = {2017}, author = {Vegiopoulos, A and Rohm, M and Herzig, S}, title = {Adipose tissue: between the extremes.}, journal = {The EMBO journal}, volume = {36}, number = {14}, pages = {1999-2017}, pmid = {28623240}, issn = {1460-2075}, mesh = {Adipokines ; Adipose Tissue/*pathology ; Animals ; Atrophy/pathology/physiopathology ; *Energy Metabolism ; Homeostasis ; Humans ; *Lipid Metabolism ; Obesity/pathology/physiopathology ; }, abstract = {Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity-related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.}, } @article {pmid28618949, year = {2017}, author = {Zhao, HY and Han, Y and Wang, J and Yang, LH and Zheng, XY and Du, J and Wu, GP and Wang, EH}, title = {IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {6}, pages = {1010428317705769}, doi = {10.1177/1010428317705769}, pmid = {28618949}, issn = {1423-0380}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal/*genetics/pathology/surgery ; Cyclin D1/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Prognosis ; Proto-Oncogene Proteins c-myc/genetics ; Survival Analysis ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; ras GTPase-Activating Proteins/*genetics ; }, abstract = {IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.}, } @article {pmid28615042, year = {2017}, author = {Darekar, A and Lamontagne, A and Fung, J}, title = {Locomotor circumvention strategies are altered by stroke: I. Obstacle clearance.}, journal = {Journal of neuroengineering and rehabilitation}, volume = {14}, number = {1}, pages = {56}, pmid = {28615042}, issn = {1743-0003}, support = {MOP- 77548//Canadian Institutes of Health Research/International ; }, mesh = {Adult ; Aged ; Female ; Gait ; Humans ; *Locomotion ; Male ; Middle Aged ; Orientation ; Paresis/etiology/physiopathology ; Psychomotor Performance ; Stroke/*psychology ; Stroke Rehabilitation/methods ; User-Computer Interface ; Walking ; }, abstract = {BACKGROUND: Functional locomotion requires the ability to adapt to environmental challenges such as the presence of stationary or moving obstacles. Difficulties in obstacle circumvention often lead to restricted community ambulation in individuals with stroke. The objective of this study was to contrast obstacle circumvention strategies between post-stroke (n = 12) and healthy individuals (n = 12) performing locomotor and perceptuomotor (joystick navigation) tasks with different obstacle approaches.

METHODS: Participants walked and navigated with a joystick towards a central target, in a virtual environment simulating a large room, while avoiding an obstacle that either remained stationary at the pre-determined point of intersection or moved from head-on or diagonally 30° left/right. The outcome measures included dynamic clearance (DC), instantaneous distance from obstacle at crossing (IDC), number of collisions and preferred side of circumvention. These measures were compared between groups (stroke vs. healthy), obstacle parameter (stationary vs. moving head-on) and direction of approach (left/paretic vs. right/non-paretic).

RESULTS: DC was significantly larger when circumventing a moving obstacle that approached head-on as compared to a stationary obstacle for both groups during both tasks, while not significantly different in either diagonal approach in either group. IDC was smaller in the stroke group while walking and larger in both groups during joystick navigation when avoiding moving as compared to stationary obstacle. IDC was significantly larger in the stroke group compared to controls for diagonal approaches during walking, wherein two different strategies emerged amongst individuals with stroke: circumventing to the same (Vsame n = 6) or opposite (Vopp n = 4) side of obstacle approach. This behavior was not seen in the perceptuomotor task, wherein post-stroke participants circumvented to opposite side of the obstacle approach as seen in healthy participants. In the locomotor task, the Vsame subgroup that had greater functional limitations used larger DC as compared to the Vopp subgroup and healthy individuals. The remaining two individuals with stroke collided with obstacles in >50% trials of either obstacle approach. The underlying mechanisms for collision were however different for both individuals.

CONCLUSION: Avoidance strategies in individuals with stroke can vary depending on the individual locomotor capabilities and obstacle characteristics.}, } @article {pmid28612598, year = {2017}, author = {Chaveepojnkamjorn, W and Pichainarong, N and Thotong, R and Sativipawee, P and Pitikultang, S}, title = {Relationship between Breast Cancer and Oral Contraceptive Use among Thai Premenopausal Women: a Case-Control Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {5}, pages = {1429-1433}, pmid = {28612598}, issn = {2476-762X}, abstract = {Background: Breast cancer (BC) is an important issue both in medicine and public health as it is the leading malignancy with high incidence and mortality among women worldwide. The objective of this research was to determine the associations of BC with oral contraceptive (OC) use among Thai premenopausal women (TPW). Materials and Methods: A case-control study was conducted among TPW attending the National Cancer Institute, with 257 cases and 257 controls in 2013-2014. Cases and controls were matched by age (± 5 years), residential area and duration of attendance. Data were collected with a questionnaire that comprised 2 sections: part 1 socio-demographic characteristics, and part 2 health risk behavior and reproductive factors. The obtained data were analyzed using descriptive and analytic statistics with a computerized statistical package. Results: The study participants were mainly 40-44 years old (60 %) with an average age of 39 years. The major BC type was invasive ductal carcinoma (91.8%). Multiple unconditional logistic regression analysis, controlling for possible confounding factors, revealed that TPW with OC use increased the risk of BC by a factor of over 3 times (ORadj=3.39, 95%CI =1.99-5.75). In addition, the greater the duration of OC, the greater the risk (ORadj 6-10 yrs=3.91, 95%CI = 1.99-7.64, ORadj >10 yrs=4.23, 95%CI = 2.05-8.71). Conclusions: From our findings, a surveillance system of cancer risk with OC use should be conducted, accompanied by an exercise promotion campaign among risk groups, providing information and counseling for physical exercise and physical activities, weight control and basic adjustment for a healthy lifestyle to reduce BC.}, } @article {pmid28612228, year = {2017}, author = {De Brot, M and Koslow Mautner, S and Muhsen, S and Andrade, VP and Mamtani, A and Murray, M and Giri, D and Sakr, RA and Brogi, E and King, TA}, title = {Pleomorphic lobular carcinoma in situ of the breast: a single institution experience with clinical follow-up and centralized pathology review.}, journal = {Breast cancer research and treatment}, volume = {165}, number = {2}, pages = {411-420}, pmid = {28612228}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Biopsy ; Breast Carcinoma In Situ/diagnosis/*pathology/therapy ; Carcinoma, Lobular/diagnosis/*pathology/therapy ; Combined Modality Therapy ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Multimodal Imaging/methods ; }, abstract = {PURPOSE: The natural history of pleomorphic lobular carcinoma in situ (PLCIS) remains largely unknown.

METHODS: A pathology database search (1995-2012) was performed to identify patients diagnosed with an LCIS variant. Patients with synchronous breast cancer and/or no evidence of pleomorphism were excluded. Original slides were re-evaluated by three pathologists to identify a consensus cohort of PLCIS. Borderline lesions with focal atypia were classified as LCIS with pleomorphic features (LCIS-PF). Clinical data were obtained from medical records.

RESULTS: From 233 patients, we identified 32 with an LCIS variant diagnosis and no concurrent breast cancer. Following review, 16 cases were excluded due to lack of pleomorphism. The remaining 16 were classified as PLCIS (n = 11) and LCIS-PF (n = 5). 12/16 patients were treated with surgical excision ± chemoprevention. Patients with a prior breast cancer history and those having mastectomy were excluded from outcome analysis. Among the remaining 7 patients with PLCIS/LCIS-PF, 4/7 (57%) developed ipsilateral breast cancer at a median follow-up of 67 months. Median age at the time of breast cancer diagnosis was 56 years old and median time from PLCIS/LCIS-PF to cancer diagnosis was 59 months (range 45-66 months). The four cancers included 1 invasive lobular carcinoma (ILC), 1 microinvasive ILC, 1 invasive ductal carcinoma, and 1 ductal carcinoma in situ.

CONCLUSIONS: We confirm that PLCIS in isolation is indeed a rare entity, further contributing to the difficulty in determining the actual risk conferred by this lesion. Long-term follow-up data on larger cohorts are needed to define standardized management and outcomes for patients with PLCIS.}, } @article {pmid28610466, year = {2018}, author = {Ben-David, BM and Icht, M}, title = {The Effect of Practice and Visual Feedback on Oral-Diadochokinetic Rates for Younger and Older Adults.}, journal = {Language and speech}, volume = {61}, number = {1}, pages = {113-134}, doi = {10.1177/0023830917708808}, pmid = {28610466}, issn = {0023-8309}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aging/*psychology ; Biomechanical Phenomena ; *Cues ; *Feedback, Sensory ; *Formative Feedback ; Humans ; *Motor Skills ; Mouth/*physiology ; Reaction Time ; Speech Articulation Tests/*methods ; Time Factors ; *Visual Perception ; Young Adult ; }, abstract = {Assessments of oral-diadochokinetic rates are commonly performed to evaluate oral-motor skills. However, the appropriate administration protocol is not defined, and varies across therapists, clinics and laboratories. In three experiments and an auxiliary one, this study analyzes the effects of brief (motor) practice and visual feedback on the performance of 98 younger (20-40 years old) and 78 older adults (over 65) with the sequential motion rate (SMR) version. Overall rates were significantly faster for younger over older adults. Irrespective of age-group, averaged performance was significantly better on the second round, but the third round was found to be superfluous, across experiments and age-groups. Visual feedback (using a mirror) was found to be detrimental for younger adults, eliminating the advantage reaped from a practice round. For older adults, visual feedback did not alter the effect of a practice round. Sensory (visual) degradation is presented as a possible source for this age-related difference. We discuss these findings and suggest an administration protocol for younger and older adults with the SMR version, including a total of two rounds and no visual feedback.}, } @article {pmid28607685, year = {2017}, author = {Agosto-Arroyo, E and Rosa, M and Chau, A and Khazai, L}, title = {Concurrent BRAF and PTEN mutations in melanoma of unknown origin presenting as a breast mass.}, journal = {SAGE open medical case reports}, volume = {5}, number = {}, pages = {2050313X17711064}, pmid = {28607685}, issn = {2050-313X}, abstract = {BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies.

PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast. Ultrasound showed a 1-cm solid mass, initially diagnosed as invasive ductal carcinoma on biopsy. During pre-operative workup, a second mass was identified and biopsied. Immunohistochemical stains performed on the second mass biopsy demonstrated that the neoplastic cells were positive for cytokeratin AE1/3, pan-melanoma, tyrosinase, and SOX-10 and negative for CK7, CAM5.2, and GATA-3. Subsequent workup showed widespread metastatic disease involving the liver, lungs, bones, and brain. The brain metastasis tested positive for BRAF p.V600E and PTEN p.R130Efs*4 mutations. Thorough skin and eye examination did not reveal a primary melanoma.

CONCLUSION: Only few reports have been published of melanoma presenting as a breast mass. This is an interesting case due to the clinical presentation, diagnostic challenges, and genetic mutations profile.}, } @article {pmid28598696, year = {2017}, author = {Gasparrini, S and Cimadamore, A and Mazzucchelli, R and Scarpelli, M and Massari, F and Raspollini, MR and Galosi, AB and Lopez-Beltran, A and Cheng, L and Montironi, R}, title = {Pathology and molecular updates in tumors of the prostate: towards a personalized approach.}, journal = {Expert review of molecular diagnostics}, volume = {17}, number = {8}, pages = {781-789}, doi = {10.1080/14737159.2017.1341314}, pmid = {28598696}, issn = {1744-8352}, mesh = {Biomarkers, Tumor/*metabolism ; *Carcinoma, Intraductal, Noninfiltrating/diagnosis/metabolism/pathology ; Humans ; Male ; Neoplasm Grading ; Oncogene Proteins, Fusion/*metabolism ; Precision Medicine/*methods ; *Prostatic Neoplasms/diagnosis/metabolism/pathology ; }, abstract = {Treatment planning in patients with prostate neoplasms and prostate cancer (PCa) is generally based on the clinical and pathological molecular markers obtained from prostate needle biopsy and/or radical prostatectomy specimens. Area covered: Pathology of prostate neoplasms is evolving rapidly. Emerging trends include new additions to the 2016 World Health Organization (WHO) tumor classification as well as expanded diagnostic utility of biomarkers and molecular testing in tissue specimens, liquid biopsies and urinary samples, with the following purposes: diagnosis, prognosis and prediction. Expert commentary: The new additions to the 2016 WHO tumor classification, which include pathological definition of Intraductal carcinoma of the prostate (IDC-P) and of a new grading system for PCa, as well as identification of molecular markers, such as TMPRSS2-ERG and AR-V7, may pave the way to personalized therapy for patients with prostate tumors.}, } @article {pmid28597470, year = {2018}, author = {Gomberawalla, A and Liou, P and Martinez, R and Rajpara, R and Connolly, E and Horowitz, D and Feldman, S}, title = {Breast conservation for male breast cancer: Case report of intraoperative radiation.}, journal = {The breast journal}, volume = {24}, number = {1}, pages = {74-77}, doi = {10.1111/tbj.12847}, pmid = {28597470}, issn = {1524-4741}, mesh = {Breast Neoplasms, Male/pathology/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/*surgery ; Combined Modality Therapy/methods ; Humans ; Intraoperative Care/methods ; Male ; Mastectomy, Segmental/methods ; Middle Aged ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62-year-old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow-up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.}, } @article {pmid28596561, year = {2017}, author = {Li, XL and Xu, HX and Li, DD and He, YP and Yue, WW and Xu, JM and Liu, BJ and Sun, LP and Fang, L}, title = {A Risk Model based on Ultrasound, Ultrasound Elastography, and Histologic Parameters for Predicting Axillary Lymph Node Metastasis in Breast Invasive Ductal Carcinoma.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {3029}, pmid = {28596561}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biomarkers, Tumor ; Biopsy ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal/*diagnostic imaging/metabolism/*pathology ; *Elasticity Imaging Techniques ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; ROC Curve ; Retrospective Studies ; *Ultrasonography/methods ; }, abstract = {To develop a risk model for predicting axillary lymph node metastasis (LNM) in patients with breast invasive ductal carcinoma (IDCs) using ultrasound (US), US elastography of virtual touch tissue imaging (VTI) and virtual touch tissue imaging & quantification (VTIQ), and histologic parameters. This study included 162 breast IDCs in 162 patients. Univariate and multivariate analyses were used to identify the risk factors and a risk model was created. The results found that 64 (39.5%) of 162 patients had axillary LNMs. The risk score (RS) for axillary LNM was defined as following: RS = 1.3 × (if lesion size ≥20 mm) + 2.6 × (if taller than wide shape) + 2.2 × (if VTI score ≥5) + 3.9 × (if histological grade III) + 1.9 × (if positive C-erbB-2). The rating system was divided into 6 stages (i.e. Stage I, Stage II, Stage III, Stage IV, Stage V, and Stage VI) and the associated risk rates in terms of axillary LNM were 0% (0/19), 6.1% (2/33), 7.7% (3/39), 65.5% (19/29), 92.3% (24/26), and 100% (16/16), respectively. The risk model for axillary LNM established in the study may facilitate subsequent treatment planning and management in patients with breast IDCs.}, } @article {pmid28595037, year = {2017}, author = {Lin, X and Hong, S and Huang, J and Chen, Y and Chen, Y and Wu, Z}, title = {Plasma apolipoprotein A1 levels at diagnosis are independent prognostic factors in invasive ductal breast cancer.}, journal = {Discovery medicine}, volume = {23}, number = {127}, pages = {247-258}, pmid = {28595037}, issn = {1944-7930}, mesh = {Adult ; Apolipoprotein A-I/*blood ; Breast Neoplasms/*blood/*mortality/therapy ; Carcinoma, Ductal/*blood/*mortality/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Proteins/*blood ; Retrospective Studies ; Survival Rate ; }, abstract = {Strong evidence exists indicating that the risk of breast cancer (BC) occurrence is influenced by complex internal environmental factors, including blood lipid and lipoprotein components. However, the roles of these components in BC development and progression remain controversial. This study examined whether serial serum lipid and lipoprotein measurements were associated with breast cancer risk and whether lipoproteins had BC prognostic properties. We compared the plasma-related parameter levels, including lipid and lipoprotein levels between 299 patients with invasive ductal breast cancer, also known as invasive ductal carcinoma (IDC), and 200 healthy donors. We performed univariate and multivariate logistic regression analyses to assess overall survival (OS) and disease-free survival (DFS). We found that the serum glucose, triacylglycerol, and low-density lipoprotein levels were significantly higher in patients with IDC than in healthy donors. However, high-density lipoprotein and apolipoprotein A1 (apoA1) levels were lower in patients with IDC than in healthy donors. Multivariate regression analysis demonstrated that elevated apoA1 levels were associated with a reduced risk of IDC, and univariate analysis showed that patients with IDC with lower apoA1 levels at diagnosis had larger tumors than patients with high apoA1 levels. Moreover, patients with IDC with lower apoA1 levels were more likely to have positive axillary lymph nodes, and were diagnosed at more advanced disease stages than patients with high apoA1 levels. We used a Cox regression model to assess the relationships between the above parameters and DFS and OS, after adjusting for tumor T and N stages, which were determined using the TNM classification system, and immunohistochemical subtypes. We found that lower apoA1 levels at diagnosis were associated with poor DFS and OS. At 60 months of follow-up, the DFS rate is 74.5% in the apoA1 L1 group, 89.9% in apoA1 L2 group, and 93.1% in apoA1 L3 group (p=0.0002). Similarly, the OS rate is 78.2% in apoA1 L1 group, 91.3% in apoA1 L2 group, and 93.7% in apoA1 L3 group (p=0.0012). In conclusion, our data indicate that low apoA1 levels are an independent predictor of the poor clinical outcomes in IDC patients.}, } @article {pmid28593462, year = {2017}, author = {Holtmaat, K and van der Spek, N and Witte, BI and Breitbart, W and Cuijpers, P and Verdonck-de Leeuw, IM}, title = {Moderators of the effects of meaning-centered group psychotherapy in cancer survivors on personal meaning, psychological well-being, and distress.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {25}, number = {11}, pages = {3385-3393}, pmid = {28593462}, issn = {1433-7339}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; 4864//KWF Kankerbestrijding/International ; }, mesh = {Cancer Survivors/*psychology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/*psychology ; Outcome Assessment, Health Care ; Psychotherapy, Group/*methods ; }, abstract = {PURPOSE: There is evidence to support that meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention for improving personal meaning and psychological well-being, as well as reducing psychological distress. In order to investigate which subpopulations MCGP-CS specifically benefits, this explorative study aims to analyze potential sociodemographic, clinical, and psychosocial factors that may moderate the effects.

METHODS: Cancer survivors (N = 114) were randomly assigned to MCGP-CS, or care as usual (CAU). Potential moderators included age, sex, relationship, education, employment, religion, cancer type, tumor stage, cancer treatment, time since treatment, anxiety, depression, other negative life events, and previous psychological treatment. Outcome measures were the Personal Meaning Profile (PMP), Scales of Psychological Well-Being (SPWB), and the Hospital Anxiety and Depression Scale (HADS). Assessment took place at baseline, post-intervention (short-term), and 3- and 6-month follow-ups (long-term). For each moderator, separate short-term and long-term linear mixed models were built.

RESULTS: Short-term effect of MCGP-CS was moderated by (male) sex (on HADS-D; F(1,98) = 6.1, p = .015) and (a high level of) depressive symptoms at baseline (on SPWB; F(1,93) = 5.7, p = .019). Long-term effect of MCGP-CS was moderated by (not having received) previous psychological treatment (on HADS-total; F(3253) = 3.4, p = .017).

CONCLUSIONS: Most sociodemographic and clinical characteristics do not appear to moderate the positive effect of MCGP-CS on personal meaning. However, MCGP-CS appears to reduce depressive symptoms, particularly in males, and to improve purpose in life of survivors with depressive symptoms. In the long-term, MCGP-CS appears to reduce psychological distress in survivors who had not received psychological treatment in the past year.

TRIAL REGISTRATION: NTR3571.}, } @article {pmid28592128, year = {2017}, author = {Li, J and Zhang, X and Zheng, L and Liu, Y}, title = {Association of nuclear FOXP3 expression with low Ki67 index and better prognosis in patients with breast invasive ductal carcinoma.}, journal = {Neoplasma}, volume = {64}, number = {5}, pages = {754-761}, doi = {10.4149/neo_2017_514}, pmid = {28592128}, issn = {0028-2685}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Forkhead Transcription Factors/genetics/*metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*metabolism ; Prognosis ; }, abstract = {Recent studies have provided clear evidence that some types of human cancer cells expressed Forkhead Box Protein 3 (FOXP3). However, the presence and role of FOXP3 in breast cancer are still contradictory up to now. In this study, we detected the expression of FOXP3 protein by immunohistochemistry in 123 cases of breast invasive ductal carcinoma. It exhibited that the subcellular localization of FOXP3 expression in breast cancer cells is heterogeneous. In nucleus, FOXP3 expression ratio was 47.97% (59/123) and the nuclear FOXP3 expression was significantly associated with lower Ki67 index (P=0.041), negative vessel tumor embolus (P=0.024). It was also significantly correlated with the molecular subtypes of breast cancer (P=0.002), displaying the highest ratio in the Luminal A subtype (68.18%). Kaplan-Meier analysis indicated that high nuclear FOXP3 expression was associated with better overall survival (OS) (94.92% vs. 82.81%, P=0.022) and disease-free survival (DFS) (91.53% vs. 76.56%, P=0.026). Moreover, nuclear FOXP3 represented an independent prognostic factor for OS (P =0.033) in multivariate analysis. However, in cytoplasm, FOXP3 expression ratio was 63.41% (78/123) and no statistic prognostic significance was found. Thus, our data demonstrated that nuclear FOXP3 expression correlated with low Ki-67 index and better outcome in breast invasive ductal carcinoma, indicating that FOXP3 acted as a potential prognostic marker for breast cancer.}, } @article {pmid28591263, year = {2017}, author = {Rodrigues, FT and Klemig, LR and Cardozo, MRP and Alves, PC and Aguiar, VM and Lessa, CS}, title = {Myiasis associated with an invasive ductal carcinoma of the left breast: case study.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {59}, number = {}, pages = {e35}, pmid = {28591263}, issn = {1678-9946}, mesh = {Adult ; Animals ; Antiparasitic Agents/therapeutic use ; Breast Neoplasms/*complications/parasitology ; Carcinoma, Ductal/*complications/parasitology ; Female ; Humans ; Ivermectin/therapeutic use ; Larva ; Myiasis/*complications/diagnosis/drug therapy ; }, abstract = {Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.}, } @article {pmid28590017, year = {2017}, author = {Shimada, H and Hasebe, T and Sugiyama, M and Shibasaki, S and Sugitani, I and Ueda, S and Gotoh, Y and Yasuda, M and Arai, E and Osaki, A and Saeki, T}, title = {Fibrotic focus: An important parameter for accurate prediction of a high level of tumor-associated macrophage infiltration in invasive ductal carcinoma of the breast.}, journal = {Pathology international}, volume = {67}, number = {7}, pages = {331-341}, doi = {10.1111/pin.12550}, pmid = {28590017}, issn = {1440-1827}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/classification/*diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/classification/*diagnosis/metabolism/pathology ; Female ; Fibrosis/metabolism/*pathology ; Humans ; Immunohistochemistry ; Macrophages/metabolism/*pathology ; Prognosis ; Scavenger Receptors, Class A/metabolism ; }, abstract = {Our group and others have previously reported that a fibrotic focus is a very useful histological factor for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 258 cases of invasive ductal carcinoma into those with and those without a fibrotic focus to investigate whether the presence of a fibrotic focus was significantly associated with the degree of tumor-associated macrophage (CD68, CD163 or CD204-positive) infiltration or whether the presence of tumor-associated macrophage infiltration heightened the malignant potential of invasive ductal carcinoma with a fibrotic focus. Multiple regression analyses demonstrated that a fibrotic focus was the only factor that was significantly associated with a high level of CD68-, CD163- or CD204-positive tumor-associated macrophage infiltration. The combined assessment of the presence or absence of a fibrotic focus and a high or a low level of CD204-positive tumor-associated macrophage infiltration clearly demonstrated that CD204-positive tumor-associated macrophage infiltration had a significant prognostic power only for patients with invasive ductal carcinoma with a fibrotic focus in multivariate analyses; CD204-positive tumor-associated macrophages might only exert a significant effect on tumor progression when a fibrotic focus is present within the invasive ductal carcinoma of the breast.}, } @article {pmid28583649, year = {2017}, author = {Raj, SD and Sweetwood, K and Kapoor, MM and Raj, KM and Nagi, C and Sepulveda, KA and Sedgwick, EL}, title = {Spindle cell lesions of the breast: Multimodality imaging and clinical differentiation of pathologically similar neoplasms.}, journal = {European journal of radiology}, volume = {90}, number = {}, pages = {60-72}, doi = {10.1016/j.ejrad.2017.02.019}, pmid = {28583649}, issn = {1872-7727}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Cell Differentiation/*radiation effects ; Diagnosis, Differential ; Female ; Humans ; Multimodal Imaging/*methods ; Prognosis ; }, abstract = {Spindle cell lesions of the breast comprise a wide-range of entities including reactive, benign and malignant proliferations. They can be pathologically challenging to differentiate as there is often immunohistochemical and morphologic similarities with characteristic spindle shaped cellular patterns. Radiological and pathological correlation is essential. Radiology detects, defines the size and extent, and assists in localizing the lesions. Pathology confirms the diagnosis and provides prognostic parameters. Familiarity with the clinicoradiological features of these diagnostically challenging lesions helps to establish an accurate pathological diagnosis and subsequent clinical decision making.}, } @article {pmid28580881, year = {2017}, author = {Wander, SA and Mayer, EL and Burstein, HJ}, title = {Blocking the Cycle: Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic, Hormone Receptor-Positive Breast Cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {25}, pages = {2866-2870}, doi = {10.1200/JCO.2017.73.9482}, pmid = {28580881}, issn = {1527-7755}, support = {T32 CA009172/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*drug therapy/*enzymology/metabolism ; Cyclin-Dependent Kinase 4/*antagonists & inhibitors ; Cyclin-Dependent Kinase 6/*antagonists & inhibitors ; Female ; Humans ; Peptide Fragments ; Randomized Controlled Trials as Topic ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old postmenopausal woman was diagnosed with breast cancer 6 years ago when she presented with a stage II (T2N1), right-sided, invasive ductal carcinoma considered grade 2 of 3 on core biopsy, with a positive fine-needle aspiration of a palpable, ipsilateral axillary lymph node. Immunohistochemical analysis was positive for estrogen and progesterone receptor expression and negative for human epidermal growth factor receptor 2 (HER2) overexpression. She received neoadjuvant dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy, followed by breast-conserving surgery and axillary lymph node dissection, which revealed residual disease in three of 11 nodes. She received adjuvant radiation therapy and initiated letrozole, with excellent compliance during the interval 6-year period. While receiving adjuvant letrozole therapy, she reported 3 months of worsening back pain. Skeletal scintigraphy and cross-sectional imaging confirmed widespread osseous metastatic disease and right supraclavicular lymph node enlargement (Fig 1). Core biopsy of the involved lymph node confirmed estrogen receptor (ER)-positive (90%), progesterone receptor-negative, HER2-negative recurrent metastatic breast cancer. The patient reported mild pain that was adequately controlled with over-the-counter anti-inflammatory medications. She has remained active with an excellent performance status.}, } @article {pmid28580342, year = {2017}, author = {Huang, X and Li, CH and Zhang, AQ and Kong, Z and Gu, WQ and Dong, JH}, title = {A simple rat model of in situ reversible obstructive jaundice in situ reversible obstructive jaundice model.}, journal = {Annals of surgical treatment and research}, volume = {92}, number = {6}, pages = {389-395}, pmid = {28580342}, issn = {2288-6575}, abstract = {PURPOSE: To develop a simple and reliable rat model of in situ reversible obstructive jaundice with low morbidity and mortality rates.

METHODS: Rats were divided into 4 groups with 8 rats each: the sham-operated (SH) group only underwent laparotomy, the control internal drainage (ID-C) group underwent choledochoduodenostomy, the new internal drainage (ID-N) group and the long-term internal drainage (ID-L) group underwent choledochocholedochostomy. Common bile duct ligation was performed in all the drainage groups 7 days before reversal procedures. All rats were sacrificed for samples 7 days after the last operation except rats of the ID-L group that survived 28 days before sacrifice. Body weight, liver function, histopathological changes, morbidity and mortality were assessed.

RESULTS: One rat died and 2 rats had complications with tube blockage in the ID-C group. No death or complications occurred in the ID-N and ID-L groups. The drainage tube remained patent in the long-term observation ID-L group. Body weight showed no significant difference between the ID-C and ID-N groups after 7 days drainage. Liver function was not fully recovered in the ID-C and ID-N groups after 7 days drainage, but statistical differences were only observed in the ID-C group compared with the SH and ID-L groups. Periportal inflammation and bile duct proliferation showed severer in the ID-C group than in the ID-N group.

CONCLUSION: The present study provided an efficient, simple, and reliable rat model that is especially suitable for long-term or consecutive studies of reversible obstructive jaundice.}, } @article {pmid28579267, year = {2017}, author = {Romeo, V and Cuocolo, R and Liuzzi, R and Riccardi, A and Accurso, A and Acquaviva, A and Buonocore, R and Imbriaco, M}, title = {Preliminary Results of a Simplified Breast MRI Protocol to Characterize Breast Lesions: Comparison with a Full Diagnostic Protocol and a Review of the Current Literature.}, journal = {Academic radiology}, volume = {24}, number = {11}, pages = {1387-1394}, doi = {10.1016/j.acra.2017.04.011}, pmid = {28579267}, issn = {1878-4046}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging ; Carcinoma, Lobular/*diagnostic imaging ; Clinical Protocols ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; ROC Curve ; Retrospective Studies ; Time Factors ; }, abstract = {RATIONALE AND OBJECTIVES: This study aimed to investigate whether a simplified breast magnetic resonance imaging (MRI) protocol consisting of a localizer, one precontrast sequence, and three time-point postcontrast sequences (at 28 seconds, 84 seconds and 252 seconds after the contrast agent administration) is suitable for the characterization of breast lesions as compared to a full diagnostic protocol (FDP). This study also aimed to review the current literature concerning abbreviated breast MRI protocols and offer an alternative protocol.

MATERIALS AND METHODS: Breast magnetic resonance (MR) examinations with detected breast lesions of 98 patients were retrospectively evaluated. Two expert radiologists in consensus reviewed the simplified breast protocol (SBP) first and only thereafter the regular FDP, recording a diagnosis for each detected lesion for both protocols. Receiver operating characteristic curve analysis was performed to determine the diagnostic performance of the SBP compared to the standard FDP. A revision of the previously reported abbreviated breast magnetic resonance protocols was also carried out.

RESULTS: A total of 180 lesions were identified; of these, 110 (61%) were malignant and 70 (39%) were benign. Of the 110 malignant lesions, 86 (78%) were invasive ductal carcinoma, 18 (16%) were invasive lobular carcinoma, and 6 (6%) were ductal carcinoma in situ. Areas under the curve for the receiver operating characteristic curves for the SBP vs the FDP were equivalent (0.98 vs 0.99, respectively; P = 0.76). The SBP could be performed in approximately 6 minutes and 58 seconds, compared to 14 minutes and 48 seconds for the FDP.

CONCLUSIONS: An SBP protocol including a late postcontrast time point is accurate for the characterization of breast lesions and was comparable to the standard FDP protocol, allowing a potential reduction of the total acquisition and interpretation times.}, } @article {pmid28576620, year = {2017}, author = {van Zelst, JCM and Balkenhol, M and Tan, T and Rutten, M and Imhof-Tas, M and Bult, P and Karssemeijer, N and Mann, RM}, title = {Sonographic Phenotypes of Molecular Subtypes of Invasive Ductal Cancer in Automated 3-D Breast Ultrasound.}, journal = {Ultrasound in medicine & biology}, volume = {43}, number = {9}, pages = {1820-1828}, doi = {10.1016/j.ultrasmedbio.2017.03.019}, pmid = {28576620}, issn = {1879-291X}, mesh = {Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Middle Aged ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {Our aim was to investigate whether Breast Imaging Reporting and Data System-Ultrasound (BI-RADS-US) lexicon descriptors can be used as imaging biomarkers to differentiate molecular subtypes (MS) of invasive ductal carcinoma (IDC) in automated breast ultrasound (ABUS). We included 125 IDCs diagnosed between 2010 and 2014 and imaged with ABUS at two institutes retrospectively. IDCs were classified as luminal A or B, HER2 enriched or triple negative based on reports of histopathologic analysis of surgical specimens. Two breast radiologists characterized all IDCs using the BI-RADS-US lexicon and specific ABUS features. Univariate and multivariate analyses were performed. A multinomial logistic regression model was built to predict the MSs from the imaging characteristics. BI-RADS-US descriptor margins and the retraction phenomenon are significantly associated with MSs (both p < 0.001) in both univariate and multivariate analysis. Posterior acoustic features and spiculation pattern severity were only significantly associated in univariate analysis (p < 0.001). Luminal A IDCs tend to have more prominent retraction patterns than luminal B IDCs. HER2-enriched and triple-negative IDCs present significantly less retraction than the luminal subtypes. The mean accuracy of MS prediction was 0.406. Overall, several BI-RADS-US descriptors and the coronal retraction phenomenon and spiculation pattern are associated with MSs, but prediction of MSs on ABUS is limited.}, } @article {pmid28576605, year = {2017}, author = {Siciliano, M and De Micco, R and Trojano, L and De Stefano, M and Baiano, C and Passaniti, C and De Mase, A and Russo, A and Tedeschi, G and Tessitore, A}, title = {Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.}, journal = {Parkinsonism & related disorders}, volume = {41}, number = {}, pages = {86-91}, doi = {10.1016/j.parkreldis.2017.05.020}, pmid = {28576605}, issn = {1873-5126}, mesh = {Aged ; Cognition Disorders/*diagnosis/*etiology ; Executive Function ; Female ; Humans ; Male ; Mental Recall ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*complications ; *Severity of Illness Index ; Statistics, Nonparametric ; }, abstract = {INTRODUCTION: The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages.

METHODS: Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II.

RESULTS: Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p < 0.0001), 10 points Clock Drawing Test (p = 0.002), and Rey-Osterrieth Complex Figure Test -copy (p < 0.0001). ORs of having cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II.

CONCLUSION: In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI.}, } @article {pmid28574667, year = {2017}, author = {Miyasato, Y and Shiota, T and Ohnishi, K and Pan, C and Yano, H and Horlad, H and Yamamoto, Y and Yamamoto-Ibusuki, M and Iwase, H and Takeya, M and Komohara, Y}, title = {High density of CD204-positive macrophages predicts worse clinical prognosis in patients with breast cancer.}, journal = {Cancer science}, volume = {108}, number = {8}, pages = {1693-1700}, pmid = {28574667}, issn = {1349-7006}, mesh = {Cell Line, Tumor ; Coculture Techniques/*methods ; Culture Media, Conditioned/pharmacology ; Female ; Humans ; MCF-7 Cells ; Macrophages/*cytology/*metabolism/pathology ; Middle Aged ; Prognosis ; Scavenger Receptors, Class A/*metabolism ; Survival Analysis ; Triple Negative Breast Neoplasms/*metabolism/pathology ; Up-Regulation ; }, abstract = {Recent studies have indicated the clinical significance of tumor-associated macrophages (TAM) in several malignant tumors including breast cancer. Although recent studies have focused on CD68-positive or CD163-positive TAM in breast cancer, no study has investigated the significance of CD204-positive TAM in breast cancer. We found that CD204 expression on macrophages was evaluated following stimulation with the conditioned medium (CM) of breast cancer cell lines. Paraffin sections of 149 breast cancer samples which were diagnosed as invasive ductal carcinoma were immunohistochemically analyzed for CD68, CD163 and CD204 expression. The results of analyses indicated that a high number of CD204-positive TAM was associated with worse clinical prognoses, including relapse-free survival, distant relapse-free survival and breast cancer-specific survival; however, neither the numbers of CD68-positive or CD163-positive TAM were associated with clinical courses. Of the clinicopathological factors investigated, estrogen receptor, Ki-67 index, hormone subtype, and histological grade were significantly related to the increased number of CD163-positive and CD204-positive TAM. These data indicate the clinical significance of CD204-positive TAM in breast cancer progression and CD204 is a marker for predicting clinical prognosis in breast cancer.}, } @article {pmid28570007, year = {2017}, author = {Shah, RB and Yoon, J and Liu, G and Tian, W}, title = {Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma.}, journal = {Histopathology}, volume = {71}, number = {5}, pages = {693-702}, doi = {10.1111/his.13273}, pmid = {28570007}, issn = {1365-2559}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Precancerous Conditions/*pathology ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; }, abstract = {AIMS: Atypical intraductal proliferation (AIP) of the prostate is histologically worse than high-grade prostate intraepithelial neoplasia, but lacks the diagnostic criteria of intraductal carcinoma of the prostate (IDC-P). The aim of this study was to compare the clinicopathological and molecular characteristics (ERG overexpression and PTEN loss) of AIP and IDC-P in core needle biopsies.

METHODS AND RESULTS: One hundred and six [84 (5.6%) of 1480 consecutive and 22 retrospectively collected] cases met the criteria: AIP only (2.4%), IDC-P only (1.3%), and IDC-P coexisting with AIP (2%). Invasive adenocarcinoma [prostate adenocarcinoma (PCa)] was present in 96% and 97% cases of AIP and IDC-P, respectively. The mean number of glands/focus and the largest gland diameter for AIP and IDC-P were 7.6 (range, 2-27) and 11.7 (range, 1-51), and 0.59 mm (range, 0.2-1.1 mm) and 0.75 mm (range, 0.2-1.8 mm), respectively. For AIP, loose cribriform architecture was the most common (93%) morphology. IDC-P-associated PCa had more aggressive pathology, including the highest combined Gleason score (GS), high-grade GS ≥ 4 + 3, and largest percentage involvement of core by PCa and percentage positive cores, than AIP-associated PCa (P < 0.05). Within the AIP group, ERG status and PTEN status were similar to those of adjacent PCa in 97% and 88% of cases, respectively. Within the IDC-P group, ERG status and PTEN status were similar among IDC-P, AIP and PCa in 96% and 91% of cases, respectively. PTEN loss was frequently heterogeneous in PCa, and localized adjacent to AIP or IDC-P.

CONCLUSIONS: AIP represents a lower-grade morphological spectrum of IDC-P, associated with intermediate-risk PCa. Patients with only AIP need an immediate repeat biopsy to rule out clinically significant PCa.}, } @article {pmid28567703, year = {2017}, author = {Baglia, ML and Malone, KE and Tang, MC and Li, CI}, title = {Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.}, journal = {Hormones & cancer}, volume = {8}, number = {4}, pages = {211-218}, pmid = {28567703}, issn = {1868-8500}, support = {R01 CA105041/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; *Alcohol Drinking/adverse effects ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/*etiology/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Population Surveillance ; Receptors, Estrogen/*metabolism ; Risk ; SEER Program ; Socioeconomic Factors ; }, abstract = {Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P trend = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P trend = 0.002) and ER+ IDC (P trend = 0.02), but inversely associated with risk of ER-IDC (P trend = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.}, } @article {pmid28567637, year = {2017}, author = {Lambein, K and Van Bockstal, M and Vandemaele, L and Van den Broecke, R and Cocquyt, V and Geenen, S and Denys, H and Libbrecht, L}, title = {Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {471}, number = {5}, pages = {575-587}, pmid = {28567637}, issn = {1432-2307}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; }, abstract = {Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.}, } @article {pmid28567140, year = {2017}, author = {Profeta, AC and Prucher, GM}, title = {Bioactive-glass in Endodontic Therapy and Associated Microsurgery.}, journal = {The open dentistry journal}, volume = {11}, number = {}, pages = {164-170}, pmid = {28567140}, issn = {1874-2106}, abstract = {INTRODUCTION: Bioactive-glass (B-G) has become a valuable adjunct to promote hard-tissue healing in many clinical situations and is of particular interest for endodontic care because of its biocompatibility, regenerative and antimicrobial properties as well as chemical composition that closely resembles the mineral make-up of human bone and dentine.

THERAPY: Initial studies suggested that bacteria-tight sealing within the entire root canal system can be achieved and successfully maintained after orthograde treatment. Promising results have also been obtained in conjunction with microsurgical techniques, with the aim of enhancing wound healing and positively influencing bone regeneration.

CONCLUSION: Here, relevant literature was explored to present a comprehensive review of the rationale, development, and current applications of B-G in Endodontology illustrating them with case reports.}, } @article {pmid28561207, year = {2017}, author = {Rice, GI and Kitabayashi, N and Barth, M and Briggs, TA and Burton, ACE and Carpanelli, ML and Cerisola, AM and Colson, C and Dale, RC and Danti, FR and Darin, N and De Azua, B and De Giorgis, V and De Goede, CGL and Desguerre, I and De Laet, C and Eslahi, A and Fahey, MC and Fallon, P and Fay, A and Fazzi, E and Gorman, MP and Gowrinathan, NR and Hully, M and Kurian, MA and Leboucq, N and Lin, JS and Lines, MA and Mar, SS and Maroofian, R and Martí-Sanchez, L and McCullagh, G and Mojarrad, M and Narayanan, V and Orcesi, S and Ortigoza-Escobar, JD and Pérez-Dueñas, B and Petit, F and Ramsey, KM and Rasmussen, M and Rivier, F and Rodríguez-Pombo, P and Roubertie, A and Stödberg, TI and Toosi, MB and Toutain, A and Uettwiller, F and Ulrick, N and Vanderver, A and Waldman, A and Livingston, JH and Crow, YJ}, title = {Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.}, journal = {Neuropediatrics}, volume = {48}, number = {3}, pages = {166-184}, pmid = {28561207}, issn = {1439-1899}, support = {309449/ERC_/European Research Council/International ; K12 NS001692/NS/NINDS NIH HHS/United States ; MR/M501803/1/MRC_/Medical Research Council/United Kingdom ; TRF-2016-09-002/DH_/Department of Health/United Kingdom ; }, mesh = {Adenosine Deaminase/*genetics ; Adolescent ; Adult ; Autoimmune Diseases of the Nervous System/diagnostic imaging/*genetics/*immunology ; Biomarkers/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interferon Type I/*metabolism ; Male ; Mutation ; Nervous System Malformations/diagnostic imaging/*genetics/*immunology ; Phenotype ; RNA-Binding Proteins/*genetics ; Young Adult ; }, abstract = {We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.}, } @article {pmid28560596, year = {2017}, author = {Petruolo, OA and Pilewskie, M and Patil, S and Barrio, AV and Stempel, M and Wen, HY and Morrow, M}, title = {Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.}, journal = {Annals of surgical oncology}, volume = {24}, number = {9}, pages = {2556-2562}, pmid = {28560596}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary/surgery ; Carcinoma, Lobular/*drug therapy/metabolism/secondary/surgery ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR).

OBJECTIVE: The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC.

METHODS: Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP).

RESULTS: From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p < 0.0001). Patients with ILC initially ineligible for BCS (n = 56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n = 183, 16 vs. 48%, p ≤ 0.0001), with a similar trend in the axilla (p = 0.086). The rates of BCS eligibility after NAC were highest in PR-/HP patients (62%) and lowest in PR+/non-HP patients (29%) [p = 0.005]. In the axilla, nodal pCR among cN+ patients (n = 301) ranged from 0 to 35% (p < 0.0001) within these groups, and was most frequent in PR-/HP patients.

CONCLUSIONS: ER+/HER2- patients most likely to benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.}, } @article {pmid28558007, year = {2017}, author = {Gweon, HM and Jeong, J and Son, EJ and Youk, JH and Kim, JA and Ko, KH}, title = {The clinical significance of accompanying NME on preoperative MR imaging in breast cancer patients.}, journal = {PloS one}, volume = {12}, number = {5}, pages = {e0178445}, pmid = {28558007}, issn = {1932-6203}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {PURPOSE: To investigate the significance of accompanying NME in invasive ductal carcinoma (IDC) on preoperative MR imaging and assess the factors affecting the significance.

METHODS: Between January 2015 and February 2016, 163 consecutive patients with IDC who underwent preoperative MR imaging and subsequent surgery were enrolled and reviewed. Index cancer mass size and total extent with accompanying NME on MR images was measured and compared with pathologic size. Positive NME was defined as pathological result of IDC or DCIS. To identify affecting factors associated with frequency of accompanying NME on MR and positive pathologic result, clinicopathologic features were compared between breast cancers with NME and without NME, and between breast cancers with positive NME and negative NME using the Student t-test or Chi-square test.

RESULTS: Of the 163 invasive breast cancers, 123(75.5%) cancers presented as only mass feature and 40(24.5%) cancers had accompanying NME around the index mass. Of the 40 accompanying NME, 22 (55%) had positive pathologic results and 18 (45%) had negative results. The HER2 positive status was significantly associated with positive pathologic results of accompanying NME (P = .016).

CONCLUSION: Accompanying NME on preoperative MR imaging showed malignant pathologic results in 55%. The HER2 positive IDC was more frequently accompanied by malignant NME.}, } @article {pmid28554530, year = {2017}, author = {Hidmark, A and Spanidis, I and Fleming, TH and Volk, N and Eckstein, V and Groener, JB and Kopf, S and Nawroth, PP and Oikonomou, D}, title = {Electrical Muscle Stimulation Induces an Increase of VEGFR2 on Circulating Hematopoietic Stem Cells in Patients With Diabetes.}, journal = {Clinical therapeutics}, volume = {39}, number = {6}, pages = {1132-1144.e2}, doi = {10.1016/j.clinthera.2017.05.340}, pmid = {28554530}, issn = {1879-114X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Count ; Diabetes Mellitus/blood/metabolism/*therapy ; *Electric Stimulation Therapy ; Female ; Hematopoietic Stem Cells/*metabolism ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; Vascular Endothelial Growth Factor Receptor-2/*metabolism ; Young Adult ; }, abstract = {PURPOSE: External electric muscle stimulation (EMS) of the thigh muscles was found to reduce pain resulting from diabetic neuropathy (DN), a vascular complication of diabetes. This study investigated circulating hematopoietic stem cells (HSCs) after EMS treatment. Impaired function of HSCs and the subpopulation endothelial progenitor cells (EPCs), important for neovascularization and endothelial repair, has been associated with DN.

METHODS: Twenty-four patients with painful DN were treated 3 times with EMS over a period of 1 week. Blood samples were collected before and after the first EMS treatment. Before a fourth treatment, neuropathic pain was evaluated and a third blood sample was collected. Cells were used for flow cytometry.

FINDINGS: Patients with painful DN reported that the pain decreased after 3 times of 1-hour treatments with EMS (Neuropathy Symptom Score: from 8 to 6, P = 0.001; Neuropathy Disability Score: from 5.5 to 5, P = 0.027, n = 24). At the end of the study, diastolic blood pressure had decreased from 80 to 70 mm Hg (P = 0.043), and plasma adrenaline and noradrenaline metabolites metanephrine and normetanephrine were reduced (both P ≤ 0.01; n = 21). A single EMS treatment caused an immediate and transient decrease in the frequency of CD34[+] HSCs in circulation (-20%; P < 0.001; n = 27). In 9 of the patients with DN, the proportion of HSCs expressing vascular endothelial growth factor receptor 2 (VEGFR2; defining the HSCs as EPCs) increased by 36% (P = 0.011) after EMS treatment. Proteins required for binding to endothelium (junctional adhesion molecule A and CD31), homing toward hypoxic tissue (C-X-C chemokine receptor type 4), and endothelial differentiation (CD31) were increased on HSCs immediately after EMS treatment. An increased frequency of VEGFR2 expression was also observed on HSCs of 6 healthy control volunteers (34%; P = 0.046) after EMS treatment, but not after sham treatment.

IMPLICATIONS: Three EMS treatments decreased symptoms of pain caused by DN and reduced diastolic blood pressure and biomarkers of stress. A single EMS treatment increased molecules mediating attachment and differentiation on the surface of HSCs in circulation. We hypothesize that the EMS-induced increase in surface attachment molecules on the HSCs caused the HSCs to leave circulation and that EMS treatment improves the function of HSCs and EPCs in vivo.}, } @article {pmid28554060, year = {2017}, author = {Takeishi, M and Shibamichi, M and Malins, A and Kurikami, H and Murakami, M and Saegusa, J and Yoneya, M}, title = {Using two detectors concurrently to monitor ambient dose equivalent rates in vehicle surveys of radiocesium contaminated land.}, journal = {Journal of environmental radioactivity}, volume = {177}, number = {}, pages = {1-12}, doi = {10.1016/j.jenvrad.2017.05.010}, pmid = {28554060}, issn = {1879-1700}, mesh = {Air Pollutants, Radioactive/*analysis ; Cesium Radioisotopes/*analysis ; Fukushima Nuclear Accident ; Japan ; Radiation Monitoring/*instrumentation ; Radioactive Fallout/*analysis ; }, abstract = {In response to the accident at Tokyo Electric Power Company's Fukushima Dai-ichi Nuclear Power Plant (FDNPP), vehicle-borne monitoring was used to map radiation levels for radiological protection of the public. By convention measurements from vehicle-borne surveys are converted to the ambient dose equivalent rate at 1 m height in the absence of the vehicle. This allows for comparison with results from other types of survey, including surveys with hand-held or airborne instruments. To improve the accuracy of the converted results from vehicle-borne surveys, we investigated combining measurements from two detectors mounted on the vehicle at different heights above the ground. A dual-detector setup was added to a JAEA monitoring car and compared against hand-held survey meter measurements in Fukushima Prefecture. The results obtained by combining measurements from two detectors were within ±20% of the hand-held reference measurements. The mean absolute percentage deviation from the reference measurements was 7.2%. The combined results from the two detectors were more accurate than those from either the roof-mounted detector, or the detector inside the vehicle, taken alone. One issue with vehicle-borne surveys is that ambient dose equivalent rates above roads are not necessarily representative of adjacent areas. This is because radiocesium is often deficient on asphalt surfaces, as it is easily scrubbed off by rain, wind and vehicle tires. To tackle this issue, we investigated mounting heights for vehicle-borne detectors using Monte Carlo gamma-ray simulations. When radiocesium is deficient on a road compared to the adjacent land, mounting detectors high on vehicles yields results closer to the values adjacent to the road. The ratio of ambient dose equivalent rates reported by detectors mounted at different heights in a dual-detector setup indicates whether radiocesium is deficient on the road compared to the adjacent land.}, } @article {pmid28553141, year = {2017}, author = {Senger, JL and Adams, SJ and Kanthan, R}, title = {Invasive lobular carcinoma of the male breast - a systematic review with an illustrative case study.}, journal = {Breast cancer (Dove Medical Press)}, volume = {9}, number = {}, pages = {337-345}, pmid = {28553141}, issn = {1179-1314}, abstract = {Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data 1973-2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options.}, } @article {pmid28553127, year = {2017}, author = {Kerwin, EM and Ferro, TJ and Ariely, R and Irwin, DE and Parikh, R}, title = {Real-world health care utilization in asthma patients using albuterol sulfate inhalation aerosol (ProAir [®] HFA) with and without integrated dose counters.}, journal = {Journal of asthma and allergy}, volume = {10}, number = {}, pages = {171-179}, pmid = {28553127}, issn = {1178-6965}, abstract = {BACKGROUND: Accurate tracking of the administered dose of asthma rescue inhalers is critical for optimal disease management and is related to reductions in rates of unscheduled health care utilization in asthma patients. There are few published data on the real-world impact of rescue inhalers with integrated dose counters (IDCs) on health care resource utilization (HRU) for asthma patients. This study evaluates HRU among users of ProAir[®] hydrofluoroalkane (HFA) (albuterol sulfate inhalation aerosol), with IDC versus without IDC, in asthma patients.

METHODS: This was a retrospective administrative claims study of asthma patients receiving a new prescription for albuterol inhalation aerosol without IDC during 2 years (January 2011-December 2012) or with IDC during the first full year after IDC implementation in the USA (July 2013-July 2014). Six months of continuous enrollment with medical and prescription drug benefits were required before and after the first prescription during the study period. Data on respiratory-related hospitalizations and emergency department (ED) visits were collected during the follow-up period.

RESULTS: A total of 135,305 (32%) patients used albuterol inhalation aerosol with IDC, and 287,243 (68%) patients received albuterol inhalation aerosol without IDC. After adjusting for baseline confounding factors, the odds ratio (OR) for experiencing a respiratory-related hospitalization (OR=0.92; 95% confidence interval [CI] 0.88-0.96) or ED visit (OR=0.92; 95% CI 0.90-0.94) was significantly lower among patients using albuterol inhalation aerosol with IDC versus without IDC.

CONCLUSION: In a real-world setting, asthma patients using ProAir HFA with IDC experienced significantly fewer hospitalizations and ED visits compared with patients using ProAir HFA without IDC. Dosage information provided by IDCs may allow providers to better understand patients' disease severity and aid in titrating controller medications and also decrease the likelihood that the canister will be empty when needed, thereby enhancing disease management and reducing HRU.}, } @article {pmid28550498, year = {2017}, author = {Micello, D and Bossi, A and Marando, A and Dainese, E and Sessa, F and Capella, C}, title = {Expression of calretinin in high-grade hormone receptor-negative invasive breast carcinomas: correlation with histological and molecular subtypes.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {471}, number = {1}, pages = {13-21}, pmid = {28550498}, issn = {1432-2307}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/metabolism ; Breast Neoplasms/*pathology ; Calbindin 2/*biosynthesis ; Carcinoma, Ductal, Breast/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Receptor, ErbB-2 ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Calretinin expression has been reported in neoplasms arising in various organs, including the breast. We investigated the relationship of calretinin expression with different histological and molecular subtypes of invasive breast carcinomas (IBCs) and its prognostic significance in high-grade female hormone receptor-negative IBCs. A total of 196 cases of IBCs of different histological subtypes were analyzed for immunohistochemical expression of calretinin, human epidermal growth factor receptor 2 (HER2), basal-like (BL), apocrine, and proliferative markers and grouped in different molecular subtypes. We found significant morphological differences in the group of formally classified invasive ductal carcinoma of no special type (IDC-NST), which we further subdivided into two types (type I IDC-NST and type II IDC-NST) according to their morphology. Calretinin expression was found in 55.1% of the IBCs and was strongly associated with carcinoma with medullary features (P = 0.014) and type II IDC-NST (P < 0.001), while type I IDC-NST correlated (P < 0.001) with a lack of calretinin expression. Among the molecular subtypes of IBC, calretinin expression was identified in a significant portion of BL breast cancers (BLBCs), while expression was poor in HER2-overexpressing and molecular-apocrine (MA) HER2-negative subtypes and even less in MA/HER2+ ones. Calretinin expression was significantly associated with high (≥50) Ki-67 (P = 0.02), but not with parameters like age, tumor size, lymph node status, overall survival (OS), and disease-free survival. Calretinin expression is most common in high-grade IBCs with histological medullary features, type II IDC-NST and BL phenotype, and is associated with high neoplastic proliferative index.}, } @article {pmid28543784, year = {2017}, author = {Chaudhuri, RK and Bojanowski, K}, title = {Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.}, journal = {International journal of cosmetic science}, volume = {39}, number = {5}, pages = {518-526}, doi = {10.1111/ics.12405}, pmid = {28543784}, issn = {1468-2494}, mesh = {Administration, Topical ; Aquaporin 3/metabolism ; Body Water ; Cadherins/genetics ; Caprylates/administration & dosage/*pharmacology ; Cell Differentiation/drug effects ; Emollients/administration & dosage ; Epidermis/*drug effects/metabolism ; Glycerol/administration & dosage ; Humans ; Hyaluronan Receptors/metabolism ; Keratinocytes/cytology/drug effects ; Oligonucleotide Array Sequence Analysis ; Placebos ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Up-Regulation/drug effects ; Water/metabolism ; }, abstract = {OBJECTIVE: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin.

METHODS: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo.

RESULTS: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin.

CONCLUSION: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing.}, } @article {pmid28541934, year = {2017}, author = {Tilak, AS and Wani, SP and Datta, A and Patil, MD and Kaushal, M and Reddy, KR}, title = {Evaluation of Ageratum conyzoides in field scale constructed wetlands (CWs) for domestic wastewater treatment.}, journal = {Water science and technology : a journal of the International Association on Water Pollution Research}, volume = {75}, number = {10}, pages = {2268-2280}, doi = {10.2166/wst.2017.119}, pmid = {28541934}, issn = {0273-1223}, mesh = {Ageratum/*physiology ; *Biodegradation, Environmental ; Nitrogen ; *Typhaceae ; Waste Disposal, Fluid/*methods ; Wastewater ; *Wetlands ; }, abstract = {Ageratum conyzoides were evaluated in field scale subsurface flow constructed wetlands (CWs) to quantify its nitrogen (N) and phosphorus (P) uptake and compare with wetland plants (Pistia stratiotes, Typha latifolia and Canna indica). The two-field scale subsurface flow CWs, located in the International Crops Research Institute for Semi-Arid Tropics, received wastewater from an urban colony. The CW1 and CW2 had the same dimensions (length:10 m, width:3 m, total depth:1.5 m and sand and gravel:1 m), similar flow rates (3 m[3]/d), hydraulic loading rates (HLRs-10 cm/d) and hydraulic retention time (HRT-5 days) from July 2014-August 2015. The vegetation in both CWs consisted of Pistia stratiotes, Typha latifolia, Canna indica, and Ageratum conyzoides, respectively. The CW1 (% reduction with respect to concentrations) reduced total suspended solids (TSS) (68%), NH4-N (26%), NO3-N (30%), soluble reactive P (SRP) (20%), chemical oxygen demand (COD) (45%) and fecal coliforms (71%), while the CW2 (%-reduction with respect to concentrations) reduced TSS (63%), NH4-N (32%), NO3-N (26%), SRP (35%), COD (39%) and fecal coliforms (70%). Ageratum conyzoides can be used in combination with Pistia stratiotes, Typha latifolia and Canna indica to enhance removal of excessive N, P and fecal coliforms from domestic wastewater.}, } @article {pmid28541858, year = {2017}, author = {Jean-Louis, CJ and Masdon, J and Smith, B and Battles, O and Dale, P}, title = {The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.}, journal = {The American surgeon}, volume = {83}, number = {5}, pages = {482-485}, pmid = {28541858}, issn = {1555-9823}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*epidemiology/pathology/therapy ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Carcinoma, Lobular/*epidemiology/pathology/therapy ; Female ; Humans ; Incidence ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*epidemiology/pathology/therapy ; Retrospective Studies ; Risk Factors ; }, abstract = {For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.}, } @article {pmid28540335, year = {2017}, author = {Coombes, RC and Caballero, OL and Shousha, S and Ghaem-Maghami, S and Woodley-Barker, L and Wilhelm-Benartzi, CS and Neville, AM}, title = {NY-ESO-1 expression in DCIS: A new predictor of good prognosis.}, journal = {Oncoscience}, volume = {4}, number = {3-4}, pages = {33-40}, pmid = {28540335}, issn = {2331-4737}, support = {13392/CRUK_/Cancer Research UK/United Kingdom ; }, abstract = {BACKGROUND: At present, it is difficult to predict which patients with ductal carcinoma-in-situ (DCIS) will subsequently develop frank invasive breast cancer (IDC). A recent survey by our group has shown that NY-ESO-1 and MAGEA are both expressed in DCIS. This study was aimed at determining whether expression of these antigens was related to the later development of IDC.

RESULTS: 14 of 42 (33%) of patients developed invasive breast cancer during the follow up period. Only one of those DCIS cases that relapsed was positive for NYESO-1 at diagnosis. In contrast, DCIS samples of 15 of the 28 (54%) of those patients who remained disease-free expressed NY-ESO-1. (Permutation chi square p=0.0033).

METHODS: We identified 42 patients with DCIS, and followed them up for more than 10 years. NY-ESO-1 and MAGEA were demonstrated by immunostaining as were CD8+ infiltrates on all sections together with the conventional markers, ER, PR, and HER2.

CONCLUSIONS: Expression of NY-ESO-1 may predict those patients who will not subsequently develop invasive breast cancer and could therefore potentially be helpful in defining prognosis in patients with DCIS.}, } @article {pmid28539389, year = {2017}, author = {Scheideler, M and Herzig, S}, title = {Let's burn whatever you have: mitofusin 2 metabolically re-wires brown adipose tissue.}, journal = {EMBO reports}, volume = {18}, number = {7}, pages = {1039-1040}, pmid = {28539389}, issn = {1469-3178}, mesh = {*Adipose Tissue, Brown ; *Burns ; Humans ; }, abstract = {Brown adipose tissue (BAT) has received enormous scientific and lay attention in the recent past as its thermogenic, energy‐consuming capacities represent prime candidates for therapeutic interventions toward obesity, glucose intolerance, and diabetes even in humans. The overall positive effects of BAT activation and recruitment on systemic energy homeostasis have been largely attributed to the inherent ability of brown adipocytes to combust fatty acid and glucose energy substrates through mitochondrial uncoupling, driven by the unique expression of uncoupling protein 1 (UCP1). Two recent reports by Boutant et al and Mahdaviani et al now identify the GTPase mitofusin (Mfn) 2 as a key determinant of BAT thermogenic function that is largely independent of its previously described role in mitochondrial fusion [1,2].}, } @article {pmid28535273, year = {2018}, author = {Noon, RB and Ayalon, L}, title = {Older Adults in Public Open Spaces: Age and Gender Segregation.}, journal = {The Gerontologist}, volume = {58}, number = {1}, pages = {149-158}, doi = {10.1093/geront/gnx047}, pmid = {28535273}, issn = {1758-5341}, mesh = {Age Factors ; Aged ; Aging/*psychology ; Community Participation/psychology ; *Environment ; Female ; Games, Recreational/psychology ; Humans ; *Interpersonal Relations ; Israel/epidemiology ; Loneliness/psychology ; Male ; Sex Factors ; *Social Environment ; Social Participation/*psychology ; Urban Population ; Verbal Behavior ; }, abstract = {BACKGROUND AND OBJECTIVES: There is a substantial body of literature on the importance of the environment in the lives of older adults. Nonetheless, to date, there has been limited research on everyday activities of urban older adults in public open spaces. The present study examined the activities of older adults in public open spaces in Israel with a specific focus on age and gender as potential variables of relevance.

RESEARCH DESIGN AND METHODS: Using still photography, we systematically photographed four sessions in two different public outdoor settings attended by older Israelis. Still photographs were converted to narrative descriptions, and then coded, quantified, and compared using descriptive statistics.

RESULTS: The majority (311, 97%) of older adults arrived alone to the public setting. Of these, 44% formed a social group of two or more people, whereas the remaining older adults stayed alone. When social interactions occurred, they were primarily gender homogenous (69%); women were more likely to integrate in spontaneous social conversations and men were more likely to participate in common games.

DISCUSSIONS AND IMPLICATIONS: Our findings call attention to the important role played by the outdoor environment as a venue for social activities among older adults. The findings further stress the high levels of aloneness experienced by older adults, which do not seem to be alleviated by the mere attendance of public spaces.}, } @article {pmid28535000, year = {2017}, author = {Catalano, OA and Daye, D and Signore, A and Iannace, C and Vangel, M and Luongo, A and Catalano, M and Filomena, M and Mansi, L and Soricelli, A and Salvatore, M and Fuin, N and Catana, C and Mahmood, U and Rosen, BR}, title = {Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast.}, journal = {International journal of oncology}, volume = {51}, number = {1}, pages = {281-288}, doi = {10.3892/ijo.2017.4012}, pmid = {28535000}, issn = {1791-2423}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Staging/*standards ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals ; Retrospective Studies ; Young Adult ; }, abstract = {The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invasive ductal carcinoma of the breast. Fifty-one women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET/CT and WB-PET/MRI before treatment. A radiologist and a nuclear medicine physician reviewed in consensus the images from the three modalities and searched for occurrence, number and location of metastases. Final staging, according to each technique, was compared. Pathology and imaging follow-up were used as the reference. WB-DWI, WB-PET/CT and WB-PET/MRI correctly and concordantly staged 33/51 patients: stage IIA in 7 patients, stage IIB in 8 patients, stage IIIC in 4 patients and stage IV in 14 patients. WB-DWI, WB-PET/CT and WB-PET/MRI incorrectly and concordantly staged 1/51 patient as stage IV instead of IIIA. Discordant staging was reported in 17/51 patients. WB-PET/MRI resulted in improved staging when compared to WB-PET/CT (50 correctly staged on WB-PET/MRI vs. 38 correctly staged on WB-PET/CT; McNemar's test; p<0.01). Comparing the performance of WB-PET/MRI and WB-DWI (43 correct) did not reveal a statistically significant difference (McNemar test, p=0.14). WB-PET/MRI is more accurate in the initial staging of breast cancer than WB-DWI and WB-PET/CT, however, the discrepancies between WB-PET/MRI and WB-DWI were not statistically significant. When available, WB-PET/MRI should be considered for staging patient with invasive ductal breast carcinoma.}, } @article {pmid28534351, year = {2017}, author = {Ates, O and Sunar, V and Aslan, A and Karatas, F and Sahin, S and Altundag, K}, title = {The short-term safety of adjuvant paclitaxel plus trastuzumab - A single centre experience.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {22}, number = {2}, pages = {320-324}, pmid = {28534351}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Immunological/administration & dosage/adverse effects ; Antineoplastic Agents, Phytogenic/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism ; Chemotherapy, Adjuvant/*adverse effects/methods ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/metabolism ; Paclitaxel/administration & dosage/adverse effects ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Trastuzumab/administration & dosage/analysis ; Ventricular Function, Left/drug effects ; }, abstract = {PURPOSE: HER2-amplified breast cancer (BC) has a poor prognosis. The combination of trastuzumab with chemotherapy in the adjuvant setting decreases recurrence and improves overall survival in HER2-positive BC. However, the role of adjuvant treatment in patients with HER2-amplified small BC without lymph node involvement is still under debate. The purpose of this study was to investigate the safety of adjuvant paclitaxel and trastuzumab (APT) in this group of patients.

METHODS: A total of 87 operated early BC patients without lymph node involvement (N0) were treated with APT for 12 weeks followed by trastuzumab alone for a total of 9 months. Clinicopathological features and adverse events were analyzed.

RESULTS: The median patient age was 50 years (range 28- 82), and 51% of them were postmenopausal. The median tumor diameter was 2.4 cm (range 0.5-6), with 51% of the patients having tumor size between 2 and 3 cm. Eighty-one percent of patients had invasive ductal carcinoma (IDC), and 64% had grade 3 tumors. Adjuvant hormone therapy and adjuvant radiotherapy were administered to 65 and 54% of patients, respectively. At a median follow up of 13 months (range 6-38), one patient (1.1%, 95% CI 0-3.4) experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) and 3 patients (3.4%, 95% CI 0-6.9) experienced grade 3 neuropathy.

CONCLUSIONS: APT appears to be a safe combination in early-stage, HER2-amplified and node-negative BC.}, } @article {pmid28532133, year = {2017}, author = {Elyasinia, F and Keramati, MR and Ahmadi, F and Rezaei, S and Ashouri, M and Parsaei, R and Yaghoubi, M and Elyasinia, F and Aboutorabi, A and Kaviani, A}, title = {Neutrophil-Lymphocyte Ratio in Different Stages of Breast Cancer.}, journal = {Acta medica Iranica}, volume = {55}, number = {4}, pages = {228-232}, pmid = {28532133}, issn = {1735-9694}, mesh = {Adult ; Aged ; Blood Platelets ; Breast Neoplasms/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Inflammation/*pathology ; Iran ; Lymphocytes/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Neutrophils/*metabolism ; Prognosis ; }, abstract = {Despite many advances in the treatment of breast cancer, it is still the second most common cause of death in women in the United States. It has been shown that inflammation plays a major role in the treatment of these cancers and inflammatory factors enhance tumor growth, invasion, metastasis, and vascularization. In this study, we would like to analyze peripheral blood neutrophil-lymphocyte ratio (NLR) in breast cancer patients and its correlation with disease staging. This cross-sectional analytic study was conducted in Imam Hospital, affiliated with Tehran University of Medical Sciences; a total of 195 female patients with breast cancer met the inclusion criteria. All of the patients had a complete blood count with leukocyte differential performed before chemotherapy. Medical records including pathology reports were also available. Data for all patients were collected prior to any surgical intervention. Exclusion criteria included clinical evidence of active infection, presence of hematological disorders, acute as well as chronic inflammatory or autoimmune diseases, or prior steroid therapy. Higher platelet count was significantly associated with the higher stage. The stage was not associated with the hemoglobin level. There was no association between the tumor size and age of patients with NLR. There was a significant relationship between NLR and IDC. There was a significant relationship between IDC and NLRs of less than 8.1 and greater than 3.3. There was a significant relationship between NLR and vascular invasion. There was no association between NLR and estrogen receptor and HER2. There was no significant relationship between the PLR and the cancer stage. In this study, NLR showed a significant relation with the disease staging. As the NLR increases the stage increases as well. Therefore, this ratio may be helpful in the preoperative evaluation of patients with breast cancer.}, } @article {pmid28531310, year = {2017}, author = {Lu, XM and Batugedara, G and Lee, M and Prudhomme, J and Bunnik, EM and Le Roch, KG}, title = {Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.}, journal = {Nucleic acids research}, volume = {45}, number = {13}, pages = {7825-7840}, pmid = {28531310}, issn = {1362-4962}, support = {R01 AI106775/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Animals ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Genes, Protozoan ; Humans ; Malaria, Falciparum/blood/parasitology ; Plasmodium falciparum/*genetics/growth & development/pathogenicity ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/*genetics/metabolism ; Sequence Analysis, RNA ; Transcription, Genetic ; }, abstract = {Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets.}, } @article {pmid28527079, year = {2017}, author = {Ranieri, A and Cavaliere, M and Sicignano, S and Falco, P and Cautiero, F and De Simone, R}, title = {Endolymphatic hydrops in idiopathic intracranial hypertension: prevalence and clinical outcome after lumbar puncture. Preliminary data.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {38}, number = {Suppl 1}, pages = {193-196}, pmid = {28527079}, issn = {1590-3478}, mesh = {Adult ; Endolymphatic Hydrops/diagnostic imaging/*epidemiology/*therapy ; Female ; Follow-Up Studies ; Humans ; Intracranial Hypertension/diagnostic imaging/*epidemiology/*therapy ; Male ; Middle Aged ; Prevalence ; Spinal Puncture/*trends ; Treatment Outcome ; Young Adult ; }, abstract = {Idiopathic intracranial hypertension is characterized by raised intracranial pressure (ICP) without any underlying pathology, presenting with (IIH) or without papilledema (IIHWOP). Headache, often on daily basis, is the most frequent symptom. Among audiovestibular symptoms, tinnitus and dizziness are commonly reported, while vertigo and hearing impairment are infrequent reports. Endolymphatic hydrops (ELH) is the typical histopathologic feature of Ménière disease, a condition featured by episodes of vertigo, dizziness, fluctuating hearing loss, tinnitus, and aural fullness. Evidences suggest that ICP is transmitted to inner ear. The aim of this study is to investigate the prevalence of ELH symptoms in IIH/IIHWOP and the relationship between the raised ICP and ELH. The prevalence of chronic headache and of ELH symptoms was investigated in a consecutive series of IIH/IIHWOP patients, and a standard audiometry with hearing threshold measurement (pure-tone average-PTA) was performed. Differences in chronic headache and ELH symptoms prevalence and changes of PTA threshold were calculated after ICP normalization by lumbar puncture (LP). Thirty-one patients (17 with IIH and 14 with IIHWOP) were included. Before LP, chronic headache was present in 93.5%. The percentages of patients reporting tinnitus, dizziness, vertigo, and aural fullness were 67.7, 77.4, 22.6, and 61.3%, respectively. Headache frequency as well as ELH symptoms and PTA significantly improved after LP. The improvement of PTA and of ELH symptoms observed after LP in this series of IIH/IIHWOP patients indicates that a raised ICP, a condition known to be involved in the progression and refractoriness of migraine pain, has also a role in ELH. We propose that intracranial hypertension may represent the shared pathogenetic step explaining the large epidemiological comorbidity between migraine and vestibular symptoms, at present conceptualized as "vestibular migraine."}, } @article {pmid28523155, year = {2017}, author = {Yang, X and Zhang, Z and Jia, X and Zhang, Y and Mu, T and Zhou, B and Li, L and Fu, D and Hu, X and Xiong, S}, title = {High expression of PLA2G16 is associated with a better prognosis in HER2-positive breast cancer.}, journal = {Journal of thoracic disease}, volume = {9}, number = {4}, pages = {1002-1011}, pmid = {28523155}, issn = {2072-1439}, abstract = {BACKGROUND: PLA2G16 functions as a phosphatase in metabolism and its abnormal expression is closely associated with tumor progression. The aim of this study is to investigate the prognosis value of PLA2G16 in breast cancer.

METHODS: A tissue microarray including 200 invasive ductal carcinoma specimens was constructed. Immunohistochemistry was performed to determine the PLA2G16 expression status. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of PLA2G16. The Multivariate Cox regression analysis was performed to identify whether PLA2G16 was an independent prognostic factor.

RESULTS: In our retrospective study, Kaplan-Meier analysis showed that elevated PLA2G16 expression was correlated with improved DFS (P=0.032) in the whole breast cancer patients. In further subgroup analysis, PLA2G16 overexpression was found to be associated with prolonged DFS (P=0.018) in HER2-positive breast cancer patients. More importantly, Multivariate analysis suggested that PLA2G16 was a significant independent prognostic factor in HER2-enriched patients [hazard ratio (HR) =0.151; 95% confidence interval (CI) =0.034-0.672; P=0.013].

CONCLUSIONS: Our study evaluated the prognostic significance of PLA2G16 in patients with HER2-positive breast cancer and confirmed the relevance of this metabolism-related gene in patient outcome.}, } @article {pmid28521483, year = {2017}, author = {Dias, MF and Blumenstein, R and Russo, J}, title = {Use of laser capture microdissection allows detection of loss of heterozygosity in chromosome 9p in breast cancer.}, journal = {Oncology letters}, volume = {13}, number = {5}, pages = {3831-3836}, pmid = {28521483}, issn = {1792-1074}, abstract = {The present study was designed to determine whether loss of heterozygosity (LOH) in the p arm of chromosome 9 in invasive ductal carcinoma of the breast is detected during the neoplastic progression of the disease. Using laser capture microdissection (LCM) epithelial cells were isolated from 14 invasive ductal carcinoma cases (IDC), ductal carcinomas in situ (DCIS), normal mammary lobules, skin and/or lymph nodes of paraffin embedded tissue sections. LOH analysis of chromosome 9p was performed utilizing the microsatellite markers D9S199, D9S157, D9S171, D9S265 and D9S270. The highest frequency of LOH was observed in invasive ductal carcinomas, which reached a maximum at the 9p22-23 chromosomal location (D9S157). In addition, DCIS lesions presented a high frequency of LOH in 9p22-23 (D9S157), followed by 9p21 (D9S171), D9S199 and D9S265, which were similar in frequency to those observed in IDC. A novel finding was the intralesional heterogeneity in LOH within the same DCIS or IDC case. This is an indication that clones of cells that differ in genetic composition coexist in the same lesion. Notably, phenotypically normal breast tissues adjacent to IDC or DCIS exhibited LOH at D9S157 and/or D9S171. Together, these data indicate that LOH of chromosome arm 9p occurs very early in the progression of cancer and that different clones of cells co-exist within a single tumor.}, } @article {pmid28521436, year = {2017}, author = {Cardoso-Coelho, LP and Borges, RS and Alencar, AP and Cardoso-Campos-Verdes, LM and da Silva-Sampaio, JP and Borges, US and Gebrim, LH and da Silva, BB}, title = {Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer.}, journal = {Oncology letters}, volume = {13}, number = {5}, pages = {3299-3302}, pmid = {28521436}, issn = {1792-1074}, abstract = {The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology.}, } @article {pmid28512126, year = {2017}, author = {Lo, PK and Zhang, Y and Yao, Y and Wolfson, B and Yu, J and Han, SY and Duru, N and Zhou, Q}, title = {Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {27}, pages = {11466-11484}, pmid = {28512126}, issn = {1083-351X}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Line, Tumor ; Epithelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; Mice, Nude ; MicroRNAs/metabolism ; Myeloid Cells/*metabolism/pathology ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Neoplasm Transplantation ; RNA, Neoplasm/metabolism ; *Signal Transduction ; Transforming Growth Factor beta/*metabolism ; }, abstract = {The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model in vitro, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFβ1, which subsequently contributed to activating the TGFβ/Smads pathway in DCIS cells. We noted that activation of the TGFβ signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we found that TGFβ-mediated induction of oncogenic miR-10b-5p expression and down-regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFβ signaling activation.}, } @article {pmid28511883, year = {2017}, author = {Chua, MLK and Lo, W and Pintilie, M and Murgic, J and Lalonde, E and Bhandari, V and Mahamud, O and Gopalan, A and Kweldam, CF and van Leenders, GJLH and Verhoef, EI and Hoogland, AM and Livingstone, J and Berlin, A and Dal Pra, A and Meng, A and Zhang, J and Orain, M and Picard, V and Hovington, H and Bergeron, A and Lacombe, L and Fradet, Y and Têtu, B and Reuter, VE and Fleshner, N and Fraser, M and Boutros, PC and van der Kwast, TH and Bristow, RG}, title = {A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies.}, journal = {European urology}, volume = {72}, number = {5}, pages = {665-674}, doi = {10.1016/j.eururo.2017.04.034}, pmid = {28511883}, issn = {1873-7560}, support = {//CIHR/Canada ; }, mesh = {Adenocarcinoma/*genetics/mortality/pathology/therapy ; Biomarkers, Tumor/*genetics ; Disease Progression ; Disease-Free Survival ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; *Genomic Instability ; Humans ; Kaplan-Meier Estimate ; Male ; Neoplasm Invasiveness ; Netherlands ; New York City ; Ontario ; Phenotype ; Proportional Hazards Models ; Prostatic Neoplasms/*genetics/mortality/pathology/therapy ; Quebec ; RNA, Long Noncoding/*genetics ; Risk Factors ; Time Factors ; Transcriptome ; Treatment Outcome ; Tumor Hypoxia ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma.

OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors.

A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Québec-Université Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed.

IDC/CA was separately assessed for biochemical relapse risk in the Canadian and MSKCC cohorts. Both cohorts were pooled for analyses on metastasis.

RESULTS AND LIMITATION: Presence of IDC/CA independently predicted for increased risks of biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices offered the strongest discrimination for metastasis (C-index 0.805 [clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors, independently corroborated by increased SChLAP1 RNA in situ hybridization signal. Optimal treatment intensification for IDC/CA+ prostate cancer requires prospective testing.

CONCLUSIONS: The poor outcome associated with IDC and CA subpathologies is associated with a constellation of genomic instability, SChLAP1 expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer, "nimbosus" (gathering of stormy clouds, Latin), which manifests as increased metastatic capacity and lethality.

PATIENT SUMMARY: A constellation of unfavorable molecular characteristics co-occur with intraductal and cribriform subpathologies in prostate cancer. Modern imaging for surveillance and treatment intensification trials should be considered in this adverse subgroup.}, } @article {pmid28511394, year = {2017}, author = {Chavan, SS and Ravindra, S and Prasad, M}, title = {Breast Biomarkers-Comparison on Whole Section and Tissue Microarray Section.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {11}, number = {3}, pages = {EC40-EC44}, pmid = {28511394}, issn = {2249-782X}, abstract = {INTRODUCTION: Estrogen Receptor (ER), Progesterone Receptor (PR) and Her2/neu are routinely studied markers for breast carcinoma. Analysis of these biomarkers is traditionally done by Immunohistochemistry (IHC) on whole sections. These markers can also be studied on Tissue Microarray (TMA) sections. Tissue microarray is a technique where core samples from different paraffin blocks are arrayed on a single recipient block which can then be cut to yield a single section with multiple cores in it.

AIM: To compare ER, PR and Her2/neu on TMA sections with whole sections and to determine the concordance of results between the two methods.

MATERIALS AND METHODS: A TMA block was constructed by punching out 2 mm cores from appropriately marked paraffin blocks of 53 breast carcinoma cases and embedding them in the recipient block. Immunostaining of TMA sections and whole sections were performed for ER, PR and Her2/neu and the results were compared. Statistical analysis was done using chi square test/Fisher-Exact test. Kappa co-efficient, Jaccard Index and G-Index were computed.

RESULTS: Infiltrating Ductal Carcinoma-No Special Type (IDC-NST) was the predominant type of carcinoma and most of the tumours were of Grade II and III. Majority, 38/53 (71.7%) were ER/PR positive and Her2 negative and 9/53 (17%) cases were triple negative. Good concordance between whole sections and TMA sections were noted with kappa value for ER, PR and Her2/neu being 0.671, 0.754, 1.000 respectively which was statistically significant.

CONCLUSION: Immunostaining for ER, PR and Her2/neu done on TMA section using single 2 mm core were comparable with conventional whole section scores. Thus, TMA is a reliable method for evaluating these biomarkers with the advantage of being time and cost effective.}, } @article {pmid28510222, year = {2017}, author = {Ishigaki, T and Toriumi, Y and Nosaka, R and Kudou, R and Imawari, Y and Kamio, M and Nogi, H and Shioya, H and Takeyama, H}, title = {Primary ectopic breast cancer of the vulva, treated with local excision of the vulva and sentinel lymph node biopsy: a case report.}, journal = {Surgical case reports}, volume = {3}, number = {1}, pages = {69}, pmid = {28510222}, issn = {2198-7793}, abstract = {Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor was excised by the Department of Plastic Surgery of our hospital. The histology of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and immunohistochemical staining of the vulvar specimen showed the tumor cells to be 100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All margins of resection were positive for neoplastic involvement. An additional local excision of the vulva and right inguinal SLNB were performed in our department. The intraoperative frozen section was negative for metastasis, and lymph node dissection was not performed. The final pathology was negative for residual disease, and a partially normal ductal component was present. Adjuvant hormonal therapy with an aromatase inhibitor was indicated post-operatively. The patient was asymptomatic and free of detectable disease at a 6-month follow-up. Due to the rarity of this diagnosis, there are no established guidelines for treatment. Although cases in which SLNB was performed are rare, we consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva.}, } @article {pmid28506312, year = {2017}, author = {Sameni, M and Cavallo-Medved, D and Franco, OE and Chalasani, A and Ji, K and Aggarwal, N and Anbalagan, A and Chen, X and Mattingly, RR and Hayward, SW and Sloane, BF}, title = {Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ.}, journal = {Breast cancer research : BCR}, volume = {19}, number = {1}, pages = {56}, pmid = {28506312}, issn = {1465-542X}, support = {R01 CA131990/CA/NCI NIH HHS/United States ; R01 DK110314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/*genetics ; Mice ; Neoplasm Invasiveness/genetics/pathology ; Plasminogen Activator Inhibitor 1/*genetics ; Proteome/genetics ; Receptors, Urokinase Plasminogen Activator/*genetics ; Tissue Array Analysis ; Tumor Microenvironment/genetics ; Urokinase-Type Plasminogen Activator/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC.

METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.

RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways.

CONCLUSIONS: Our studies using MAME are, to our knowledge, the first to demonstrate a divergent interplay between MEPs and CAFs within the DCIS tumor microenvironment. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor microenvironmental regulators of DCIS progression will be critical for defining a robust and predictive molecular signature for clinical use.}, } @article {pmid28498790, year = {2017}, author = {Yoo, J and Yoon, HJ and Kim, BS}, title = {Prognostic Value of Percentage Change in Metabolic Parameters as Measured by Dual-Time Point [18]F-FDG PET/CT in Premenopausal Women with Invasive Ductal Breast Carcinoma.}, journal = {Journal of women's health (2002)}, volume = {26}, number = {10}, pages = {1131-1137}, doi = {10.1089/jwh.2016.6256}, pmid = {28498790}, issn = {1931-843X}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Positron Emission Tomography Computed Tomography/*methods ; *Premenopause ; Proportional Hazards Models ; *Radiopharmaceuticals ; Retrospective Studies ; Tumor Burden ; }, abstract = {OBJECTIVES: We retrospectively evaluated the prognostic significance of dual-time point (DTP) [18]F-FDG positron emission tomography/computed tomography (PET/CT) parameters compared with clinicopathological findings in premenopausal women with invasive ductal breast carcinoma (IDC).

MATERIALS AND METHODS: Sixty-six premenopausal women (mean age: 42.7 ± 5.6, range: 29.5-51.8 years) who had pathologically confirmed IDC were enrolled. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and used to calculate percentage changes over the DTP time interval. We analyzed the prognostic significance of DTP PET/CT parameters, clinicopathological factors of pathologic tumor diameter (pTD), axillary lymph node status (ANS), nuclear grade, histologic grade, and immunohistochemistry findings using univariate and multivariate analyses.

RESULTS: Disease recurrence was observed in 22 patients. In univariate analysis, SUVmax > 7.39, MTV > 4.28, TLG > 52.38, %ΔSUVmax > 20.44, %ΔTLG > -13.86, pTD > 2.8 cm, positive ANS, estrogen receptor (ER) negativity, and triple negativity were associated with worse prognosis than those of opposite groups in recurrence-free survival (all p < 0.05). %ΔSUVmax (>20.44, p = 0.0042), TLG (>52.38, p = 0.0002), and ER negativity (p = 0.0003) were independent prognostic variables after multivariate analysis.

CONCLUSION: Percentage changes in SUVmax using DTP PET/CT and TLG were significant independent prognostic factors of disease recurrence along with ER negativity in premenopausal women with IDC.}, } @article {pmid28484924, year = {2017}, author = {Turner-Ivey, B and Smith, EL and Rutkovsky, AC and Spruill, LS and Mills, JN and Ethier, SP}, title = {Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3.}, journal = {Breast cancer research and treatment}, volume = {164}, number = {2}, pages = {349-358}, pmid = {28484924}, issn = {1573-7217}, support = {P30 CA138313/CA/NCI NIH HHS/United States ; R01 CA100724/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Transformation, Neoplastic/genetics/*pathology ; Female ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Hyperplasia ; Lactation ; Mammary Neoplasms, Experimental/genetics/*pathology ; Mice ; Mice, Transgenic ; Neoplasm Grading ; Nuclear Proteins/*genetics ; Promoter Regions, Genetic ; }, abstract = {PURPOSE: NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo.

METHODS: We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin.

RESULTS: Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50 weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ.

CONCLUSIONS: Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene.}, } @article {pmid28481705, year = {2017}, author = {Poppe, MM and Agarwal, JP}, title = {Breast Reconstruction With Postmastectomy Radiation: Choices and Tradeoffs.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {35}, number = {22}, pages = {2467-2470}, doi = {10.1200/JCO.2017.72.7388}, pmid = {28481705}, issn = {1527-7755}, mesh = {*Breast Implants ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/secondary/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mammaplasty/methods ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*radiotherapy/surgery ; Radiotherapy, Adjuvant ; Rectus Abdominis/transplantation ; *Surgical Flaps ; Transplantation, Autologous ; }, abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.}, } @article {pmid28480663, year = {2017}, author = {Lee, SJ and Choi, YY and Kim, C and Chung, MS}, title = {Correlations between Tumor to Background Ratio on Breast-Specific Gamma Imaging and Prognostic Factors in Breast Cancer.}, journal = {Journal of Korean medical science}, volume = {32}, number = {6}, pages = {1031-1037}, pmid = {28480663}, issn = {1598-6357}, mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Female ; *Gamma Rays ; Humans ; Ki-67 Antigen/genetics/metabolism ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Technetium Tc 99m Sestamibi/chemistry ; }, abstract = {The purpose of this study was to investigate the correlations between tumor-to-background ratio (TBR) obtained from breast-specific gamma imaging (BSGI) and the prognostic factors of breast cancer. Sixty-seven patients with invasive ductal carcinoma who underwent preoperative BSGI were enrolled. The BSGI images were visually scored from 1 to 5 according to a breast imaging reporting and data system (BIRADS). The TBR results obtained from positive BSGI images were compared according to the following prognostic factors: tumor size; axillary lymph node metastasis; nuclear grade (NG); histologic grade (HG); subtype; Ki-67; and the expression profile of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among 67 images, 60 were classified as a positive finding (sensitivity 89.6%). A higher TBR value was significantly correlated with tumor size ≥ 2 cm (P = 0.001), axillary lymph node metastasis (P = 0.007), high HG (P = 0.029), negative PR status (P = 0.036), and Ki-67 ≥ 14% (P = 0.007). The TBR showed a significant difference between the luminal A and non-luminal A subtypes (P = 0.007). On multivariate analysis, TBR had a high correlation with tumor size ≥ 2 cm, axillary lymph node metastasis, and negative PR status (P = 0.003, 0.048, and 0.030, respectively). A high TBR on BSGI was significantly correlated with poor prognostic factors of breast cancer. Luminal A subtype, a breast cancer subtype with more favorable prognosis, was associated with a low TBR on BSGI.}, } @article {pmid28477446, year = {2017}, author = {Wahab, N and Khan, A and Lee, YS}, title = {Two-phase deep convolutional neural network for reducing class skewness in histopathological images based breast cancer detection.}, journal = {Computers in biology and medicine}, volume = {85}, number = {}, pages = {86-97}, doi = {10.1016/j.compbiomed.2017.04.012}, pmid = {28477446}, issn = {1879-0534}, mesh = {Algorithms ; Breast Neoplasms/*diagnostic imaging/pathology ; Cell Nucleus ; Female ; Histocytochemistry ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Machine Learning ; Mitosis ; *Neural Networks, Computer ; ROC Curve ; }, abstract = {Different types of breast cancer are affecting lives of women across the world. Common types include Ductal carcinoma in situ (DCIS), Invasive ductal carcinoma (IDC), Tubular carcinoma, Medullary carcinoma, and Invasive lobular carcinoma (ILC). While detecting cancer, one important factor is mitotic count - showing how rapidly the cells are dividing. But the class imbalance problem, due to the small number of mitotic nuclei in comparison to the overwhelming number of non-mitotic nuclei, affects the performance of classification models. This work presents a two-phase model to mitigate the class biasness issue while classifying mitotic and non-mitotic nuclei in breast cancer histopathology images through a deep convolutional neural network (CNN). First, nuclei are segmented out using blue ratio and global binary thresholding. In Phase-1 a CNN is then trained on the segmented out 80×80 pixel patches based on a standard dataset. Hard non-mitotic examples are identified and augmented; mitotic examples are oversampled by rotation and flipping; whereas non-mitotic examples are undersampled by blue ratio histogram based k-means clustering. Based on this information from Phase-1, the dataset is modified for Phase-2 in order to reduce the effects of class imbalance. The proposed CNN architecture and data balancing technique yielded an F-measure of 0.79, and outperformed all the methods relying on specific handcrafted features, as well as those using a combination of handcrafted and CNN-generated features.}, } @article {pmid28475116, year = {2017}, author = {Brings, S and Fleming, T and Freichel, M and Muckenthaler, MU and Herzig, S and Nawroth, PP}, title = {Dicarbonyls and Advanced Glycation End-Products in the Development of Diabetic Complications and Targets for Intervention.}, journal = {International journal of molecular sciences}, volume = {18}, number = {5}, pages = {}, pmid = {28475116}, issn = {1422-0067}, mesh = {Animals ; Clinical Trials as Topic ; Diabetes Complications/drug therapy/*metabolism ; Glycation End Products, Advanced/*metabolism ; Glyoxal/metabolism ; Humans ; Hypoglycemic Agents/pharmacology/*therapeutic use ; Maillard Reaction/drug effects ; }, abstract = {Advanced glycation end-products (AGEs) are non-enzymatic protein and amino acid adducts as well as DNA adducts which form from dicarbonyls and glucose. AGE formation is enhanced in diabetes and is associated with the development of diabetic complications. In the current review, we discuss mechanisms that lead to enhanced AGE levels in the context of diabetes and diabetic complications. The methylglyoxal-detoxifying glyoxalase system as well as alternative pathways of AGE detoxification are summarized. Therapeutic approaches to interfere with different pathways of AGE formation are presented.}, } @article {pmid28475000, year = {2017}, author = {Wang, Y and Shen, H and Yin, Q and Zhang, T and Liu, Z and Zhang, W and Niu, Y}, title = {Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {39}, number = {5}, pages = {1010428317699754}, doi = {10.1177/1010428317699754}, pmid = {28475000}, issn = {1423-0380}, mesh = {Aged ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Middle Aged ; NIMA-Related Kinases/biosynthesis/*genetics ; Paclitaxel/*administration & dosage ; Xenograft Model Antitumor Assays ; }, abstract = {NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients (p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.}, } @article {pmid28464874, year = {2017}, author = {Han, Y and Li, J and Han, S and Jia, S and Zhang, Y and Zhang, W}, title = {Diagnostic value of endoscopic appearance during ductoscopy in patients with pathological nipple discharge.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {300}, pmid = {28464874}, issn = {1471-2407}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating ; Endoscopy/*methods ; Female ; Humans ; Mammary Glands, Human/*diagnostic imaging ; Middle Aged ; Nipple Discharge/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult ; }, abstract = {BACKGROUND: To explore the features of ductoscopic appearance that may be diagnostic in patients with pathologic nipple discharge (PND) and to discuss the diagnostic criteria for intraductal tumors.

METHODS: We reviewed 247 patients with PND but without a palpable mass who were evaluated using either surgical biopsy or excision. Data concerning patient age, duration of discharge, discharge color, and the details of endoscopic appearance were analyzed according to the pathological results.

RESULTS: The postoperative diagnosis in 61 patients (24.70%) was a nonmass lesion, and 186 patients (76.52%) had an intraductal tumor. Among those with intraductal lesions, 10 patients (4.05%) had a malignant tumor, including 4 (1.62%) with ductal carcinoma in situ and 6 (2.43%) with invasive ductal carcinoma. On univariate analysis, patients of older age with spontaneous and bloody discharge were more likely to suffer from intraductal lesions. On logistic regression analysis, bloody nipple discharge, morphology, and a broad lesion base revealed by ductoscopy showed a statistically significant correlation with malignancy (p = 0.001, p < 0.001, p = 0.022, respectively).

CONCLUSIONS: Both clinical features and endoscopic appearance are significant for the precise diagnosis of an intraductal lesion seen on ductoscopy. The endoscopic features of bloody discharge, morphology, and a broad lesion base are independent risk factors for malignancy and represent new criteria for the diagnosis of patients with PND.}, } @article {pmid28464815, year = {2017}, author = {Parker, V and Giles, M and Graham, L and Suthers, B and Watts, W and O'Brien, T and Searles, A}, title = {Avoiding inappropriate urinary catheter use and catheter-associated urinary tract infection (CAUTI): a pre-post control intervention study.}, journal = {BMC health services research}, volume = {17}, number = {1}, pages = {314}, pmid = {28464815}, issn = {1472-6963}, mesh = {Australia ; Catheter-Related Infections/epidemiology/*prevention & control ; Controlled Before-After Studies ; Cross Infection/epidemiology/prevention & control ; Evidence-Based Practice ; Hospitals ; Humans ; Incidence ; Medical Overuse/*prevention & control ; Unnecessary Procedures ; Urinary Catheterization/adverse effects/*statistics & numerical data ; Urinary Tract Infections/epidemiology/*prevention & control ; }, abstract = {BACKGROUND: Urinary tract infection (UTI) as the most common healthcare-associated infection accounts for up to 36% of all healthcare-associated infections. Catheter-associated urinary tract infection (CAUTI) accounts for up to 80% of these. In many instances indwelling urinary catheter (IDC) insertions may be unjustified or inappropriate, creating potentially avoidable and significant patient distress, embarrassment, discomfort, pain and activity restrictions, together with substantial care burden, costs and hospitalisation. Multifaceted interventions combining best practice guidelines with staff engagement, education and monitoring have been shown to be more effective in bringing about practice change than those that focus on a single intervention. This study builds on a nurse-led initiative that identified that significant benefits could be achieved through a systematic approach to implementation of evidence-based practice.

METHODS: The primary aim of the study is to reduce IDC usage rates by reducing inappropriate urinary catheterisation and duration of catheterisation. The study will employ a multiple pre-post control intervention design using a phased mixed method approach. A multifaceted intervention will be implemented and evaluated in four acute care hospitals in NSW, Australia. The study design is novel and strengthened by a phased approach across sites which allows for a built-in control mechanism and also reduces secular effects. Feedback of point prevalence data will be utilised to engage staff and improve compliance. Ward-based champions will help to steward the change and maintain focus.

DISCUSSION: This study will improve patient safety through implementation and robust evaluation of clinical practice and practice change. It is anticipated that it will contribute to a significant improvement in patient experiences and health care outcomes. The provision of baseline data will provide a platform from which to ensure ongoing improvement and normalisation of best practice. This study will add to the evidence base through enhancing understanding of interventions to reduce CAUTI and provides a prototype for other studies focussed on reduction of hospital acquired harms. Study findings will inform undergraduate and continuing education for health professionals.

TRIAL REGISTRATION: ACTRN12617000090314 . Registered 17 January 2017. Retrospectively registered.}, } @article {pmid28463676, year = {2017}, author = {Martiniuc, A and Dumitraşcu, T and Pavel, M and Stroescu, C}, title = {Simultaneous Breast and Liver Surgery in a Patient with Stage IV Triple Positive Breast Cancer - A Case Report.}, journal = {Chirurgia (Bucharest, Romania : 1990)}, volume = {112}, number = {2}, pages = {165-171}, doi = {10.21614/chirurgia.112.2.165}, pmid = {28463676}, issn = {1221-9118}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/*surgery/therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/*surgery/therapy ; Chemotherapy, Adjuvant/methods ; Female ; *Hepatectomy/methods ; Humans ; Liver Neoplasms/metabolism/*secondary/*surgery/therapy ; *Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; }, abstract = {UNLABELLED: Introduction: In the modern context of multimodal treatment strategies for cancer patients with systemic disease, the dogma that surgery has a limited role is becoming less and less valid. Although a "œcurative" approach is not possible for the majority of the cases, however, some patients with limited systemic disease and favorable tumor biology could benefit from an aggressive combined cytotoxic and surgical strategy.

CASE REPORT: A 48-year-old patient was diagnosed with an invasive ductal carcinoma with the immunohistochemistry positive for estrogen and progesterone receptors, positive Her2 and three liver metastases. After nine cycles of chemotherapy, a favorable tumor response was identified at the level of the primary tumor as well as for the liver lesions: two of the metastases have disappeared, and the third one decreased in dimensions. The patient was operated in our unit, a lumpectomy together with a level II axillary lymph nodes dissection and a non-anatomic resection of the segment V of the liver was performed. Conclusions: A subgroup of patients with stage IV breast cancer with limited liver metastases and no extrahepatic disease might benefit from an aggressive combined cytotoxic and surgical strategy regarding disease control and overall survival.}, } @article {pmid28462947, year = {2017}, author = {Zhu, YB and Zheng, K and Wu, X and Ang, LK}, title = {Enhanced stability of filament-type resistive switching by interface engineering.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {43664}, pmid = {28462947}, issn = {2045-2322}, abstract = {The uncontrollable rupture of the filament accompanied with joule heating deteriorates the resistive switching devices performance, especially on endurance and uniformity. To suppress the undesirable filaments rupture, this work presents an interface engineering methodology by inducing a thin layer of NiOx into a sandwiched Al/TaOx/ITO resistive switching device. The NiOx/TaOx interface barrier can confine the formation and rupture of filaments throughout the entire bulk structure under critical bias setups. The physical mechanism behind is the space-charge-limited conduction dominates in the SET process, while the Schottky emission dominates under the reverse bias.}, } @article {pmid28462850, year = {2017}, author = {El-Naby, NEH and Hassan Mohamed, H and Mohamed Goda, A and El Sayed Mohamed, A}, title = {Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {29}, number = {2}, pages = {77-82}, doi = {10.1016/j.jnci.2017.02.002}, pmid = {28462850}, issn = {2589-0409}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics/virology ; Carcinoma, Ductal/complications/*epidemiology/genetics/virology ; Egypt/epidemiology ; Epstein-Barr Virus Infections/complications/*epidemiology/genetics/virology ; Female ; Herpesvirus 4, Human/*pathogenicity ; Humans ; Middle Aged ; }, abstract = {BACKGROUND: A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature.

OBJECTIVES: We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center.

STUDY DESIGN: This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls.

RESULTS: Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003.

CONCLUSION: Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness.}, } @article {pmid28461813, year = {2017}, author = {Lee, DH and Kim, SS and Seong, S}, title = {A Case Report of Metastatic Breast Cancer Treated with Korean Medicine Therapy as a Substitute for Chemotherapy.}, journal = {Case reports in oncology}, volume = {10}, number = {1}, pages = {27-36}, pmid = {28461813}, issn = {1662-6575}, abstract = {The purpose of this case report is to show the potential benefit of Korean medicine therapy for treating multiple metastatic breast cancer. A 45-year-old Korean woman was diagnosed with right breast invasive ductal carcinoma in August 2012 but did not receive any treatment until October 2015 when she was diagnosed with stage 4 right breast cancer with multiple liver, bone, mesentery, retroperitoneum, and axillary lymph node metastases. After chemo-port insertion, she was treated with palliative chemotherapy and the first line of trastuzumab and paclitaxel, and the port was removed due to port infection. To treat sepsis, vancomycin and tazoperan were administered, before the third line of trastuzumab and paclitaxel was carried out. However, the patient gave up chemotherapy due to vancomycin-resistant enterococci and general weakness. Later, she received Korean medicine therapy with wild ginseng pharmacopuncture, distilled Soramdan S, Hae, and Jeobgoldan for 8 months, which led to a significant decrease of the multiple metastases. The patient was able to start walking again with the help of a walking stick. However, a new metastatic lesion was found on the right adrenal gland. This case suggests that the combination of chemotherapy and Korean medicine therapy may be valuable. Further research is indicated.}, } @article {pmid28455673, year = {2017}, author = {Wong, SM and King, T and Boileau, JF and Barry, WT and Golshan, M}, title = {Population-Based Analysis of Breast Cancer Incidence and Survival Outcomes in Women Diagnosed with Lobular Carcinoma In Situ.}, journal = {Annals of surgical oncology}, volume = {24}, number = {9}, pages = {2509-2517}, doi = {10.1245/s10434-017-5867-6}, pmid = {28455673}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*epidemiology/mortality/surgery ; Breast Neoplasms/*epidemiology/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*epidemiology/mortality/pathology ; Carcinoma, Lobular/*epidemiology/mortality/pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasms, Second Primary/*epidemiology/mortality/pathology ; Proportional Hazards Models ; SEER Program ; Survival Rate ; United States/epidemiology ; Young Adult ; }, abstract = {PURPOSE: A diagnosis of lobular carcinoma in situ (LCIS) is associated with an increased risk of developing breast cancer, although little data exist on long-term patient outcomes, including those who develop subsequent breast malignancies.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women with a histological diagnosis of LCIS between 1983 and 2014. The incidence and clinicopathologic features of subsequent malignancies were then examined, and the Kaplan-Meier method and multivariable Cox PH regression used to obtain breast cancer-specific survival (BCSS) estimates and associated hazard ratios.

RESULTS: Overall, 19,462 women swith a mean age at LCIS diagnosis of 53.7 years, and a 10- and 20-year cumulative incidence of subsequent breast malignancy of 11.3% [95% confidence interval (CI) 10.7-11.9%] and 19.8% (95% CI 18.8-20.9) met the eligibility criteria. At a median follow-up of 8.1 years (range 0-30.9) a total of 1837 primary breast cancers were diagnosed, of which 55.2% were diagnosed in the ipsilateral breast. Most breast cancers were of low/intermediate grade, hormone receptor-positive, and diagnosed in early stages. Of subsequent malignancies, invasive ductal carcinoma (IDC) distributed equally across both breasts, whereas invasive lobular carcinoma (ILC) was more likely to present in the ipsilateral breast (69.0% ILC vs. 49.2% IDC; p < 0.001). On multivariable analysis, type of surgical treatment for LCIS had no affect on long-term survival (p = 0.44). The 10- and 20-year BCSS for women with LCIS was 98.9 and 96.3%, respectively.

CONCLUSION: Women with LCIS who are diagnosed with a subsequent primary breast cancer are often diagnosed in early stages and have excellent BCSS.}, } @article {pmid28454334, year = {2017}, author = {Li, Y and Rong, G and Kang, H}, title = {Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer.}, journal = {Oncology letters}, volume = {13}, number = {3}, pages = {1856-1860}, pmid = {28454334}, issn = {1792-1074}, abstract = {Breast cancer is the most common malignant tumor in women worldwide, and accounts for an estimated 29% of new cases and 15% of cancer-associated mortalities each year. Invasive ductal carcinoma represents 70-80% of all breast cancer cases, which are responsible for the majority of breast cancer fatalities. Though great progress has been made in understanding the tumorigenesis and development of breast cancer, problems surrounding treatment persist. It was previously reported that carcinoma-associated fibroblasts (CAFs) may be closely associated with chemotherapy resistance. In the present study, primary-cultured CAFs from surgically resected breast invasive ductal cancer tissues were prepared and tested to clarify the change of gene expression profile following treatment with 20 ng/ml Taxotere[®] for 24 h through microarray analysis. In addition, quantitative polymerase chain reaction and western blotting were performed to compare the gene and protein expression of the candidate gene in CAFs prior to and following Taxotere treatment. Based on the obtained data, 35 differentially expressed genes were identified, including ACTA2, ACTC1, ACTG, ALDH1B1, AMY1A, C5orf13, CNN1, CXCR7, DDAH1, FGF1, PDLIM3, MAMLD1, MYH11, OXTR, PDLIM5, RARRES1, SERPINA3, TRIL, C14orf43, C1orf51, CXCL12, CXCL2, EGR2, EGR3, IER3, interleukin (IL)8, IRF1, JUNB, MMP1, NAV2, NFKBIA, NFKBIZ, TRIB1, WNT16 and ZC3H12A. It was observed that the expression of the candidate gene IL8 in the CAFs of breast invasive cancer following treatment with Taxotere was increased (P<0.05). Overall, elevated expression of IL8 induced by Taxotere in CAFs potentially supports the association between IL8 and chemotherapy response.}, } @article {pmid28454314, year = {2017}, author = {Itagaki, H and Yamamoto, T and Hiroi, A and Kawanishi, K and Noguchi, E and Ohchi, T and Kamio, T and Kameoka, S and Oda, H and Nagashima, Y}, title = {Synchronous and bilateral oncocytic carcinoma of the breast: A case report and review of the literature.}, journal = {Oncology letters}, volume = {13}, number = {3}, pages = {1714-1718}, pmid = {28454314}, issn = {1792-1074}, abstract = {Synchronous bilateral breast cancer is rare, and oncocytic carcinoma is an even rarer breast cancer histological subtype. In general, oncocytic tumors are defined as neoplasms with eosinophilic granular cytoplasm and have been reported in various organs. Oncocytic carcinoma of the breast was first documented by Gădăleanu and Craciun in 1987, and 48 cases have since been reported. The present study reports a case of synchronous bilateral breast oncocytic carcinoma. The patient was a 78-year-old woman. Although she exhibited no symptoms, chest computed tomography revealed three multinodular breast tumors: Two in the right breast and one in the left. Core needle biopsy was performed on the three tumors, and the patient was diagnosed with invasive ductal carcinoma with potential apocrine carcinoma. A bilateral modified radical mastectomy was performed. Surgical specimens of the three tumors revealed cord- or nest-forming tumor cells with eosinophilic granular cytoplasm. Immunohistochemically, the tumor cells were markedly positive for mitochondria. Electron microscopy of the tumor samples additionally revealed numerous mitochondria filling the cytoplasm. Based on these findings, the tumors were diagnosed as oncocytic carcinoma. The pathogenesis of oncocytic carcinoma remains to be fully elucidated; thus, additional clinicopathological studies are required.}, } @article {pmid28448389, year = {2018}, author = {Clough, KB and van la Parra, RFD and Thygesen, HH and Levy, E and Russ, E and Halabi, NM and Sarfati, I and Nos, C}, title = {Long-term Results After Oncoplastic Surgery for Breast Cancer: A 10-year Follow-up.}, journal = {Annals of surgery}, volume = {268}, number = {1}, pages = {165-171}, doi = {10.1097/SLA.0000000000002255}, pmid = {28448389}, issn = {1528-1140}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/mortality/pathology/*surgery ; Carcinoma, Lobular/mortality/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*methods ; Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the long-term oncologic outcome after oncoplastic surgery (OPS).

BACKGROUND: OPS combines wide tumor excision with reduction mammoplasty techniques thus extending breast conserving surgery to large tumors that might else be proposed a mastectomy. Little data are available about the oncologic results for breast conserving surgery of these larger tumors.

METHODS: From January 2004 until March 2016, a total of 350 oncoplastic breast reductions were prospectively entered into a database. Patients were included if their breast reshaping included a reduction mammoplasty with skin excision (Level 2 oncoplastic techniques).

RESULTS: Histologic subtypes were: invasive ductal carcinoma in 219 cases (62.6%), ductal carcinoma in situ (DCIS) in 88 cases (25.1%), and invasive lobular carcinoma in 43 (12.3%) cases. Seventy-three of the invasive cancers (27.9%) received neoadjuvant chemotherapy. The mean resection weight was 177 grams. The mean pathological tumor size was 26 mm (range 0-180 mm) and varied from 23 mm (4-180 mm) for invasive cancers to 32 mm (0-100 mm) for DCIS. Specimen margins were involved in 12.6% of the cases; 10.5% of invasive ductal, 14.7% of DCIS, and 20.9% of invasive lobular. The overall breast conservation rate was 92% and varied from 87.4% for DCIS to 93.5% for the invasive cancers. Thirty-one patients (8.9%) developed one or more postoperative complications, inducing a delay in postoperative treatments in 4.6% of patients. The median follow up was 55 months. The cumulative 5-year incidences for local, regional, and distant recurrences were 2.2%, 1.1%, and 12.4%, respectively.

CONCLUSIONS: Oncoplastic breast reductions allow wide resections with free margins and can be used for large cancers as an alternative to mastectomy.}, } @article {pmid28447922, year = {2017}, author = {Eldor, L and Shoshani, A}, title = {Are You Being Served? The Relationship between School Climate for Service and Teachers' Engagement, Satisfaction, and Intention to Leave: A Moderated Mediation Model.}, journal = {The Journal of psychology}, volume = {151}, number = {4}, pages = {359-378}, doi = {10.1080/00223980.2017.1291488}, pmid = {28447922}, issn = {1940-1019}, mesh = {Adult ; Female ; Humans ; Israel ; Male ; *Organizational Culture ; Psychology, Educational ; School Teachers/*psychology ; Schools/*organization & administration ; }, abstract = {The notion of service has been receiving increasing attention in organizational psychology literature in recent years, due to the client-oriented managerial movement. Yet, little to no attention has been paid to the service notion in educational psychology despite its high relevance to educational settings, given the pressure to be more service-oriented and possess a client-focused state of mind. The present study explores the notion of service in school domains by examining the joint effects of climate for service and the internal service in schools on teachers' work attitudes: work engagement, job satisfaction, and intention to leave their work. The notion of climate for service emphasizes the school's attitude of teachers as service providers to its clients (students and their parents); internal climate emphasizes the school's attitude of providing service to its teaching staff. The study was conducted via a sample of 423 teachers from 30 different schools in Israel. We hypothesized that the indirect relationship between the climate for service and teachers' job satisfaction and intention to leave work would be mediated by teacher work engagement. Our findings supported this hypothesis. Moreover, this indirect relationship via teacher work engagement was demonstrated most strongly when the internal service quality received was high, providing teachers with the capability to deliver what the service climate motivates them to do. Therefore, service-oriented resources-both climate for service and internal service-may be crucial in affecting teachers work attitudes and should be specifically targeted by principals and other educational decision makers.}, } @article {pmid28445946, year = {2017}, author = {Zhang, N and Zhang, H and Chen, T and Yang, Q}, title = {Dose invasive apocrine adenocarcinoma has worse prognosis than invasive ductal carcinoma of breast: evidence from SEER database.}, journal = {Oncotarget}, volume = {8}, number = {15}, pages = {24579-24592}, pmid = {28445946}, issn = {1949-2553}, mesh = {Adenocarcinoma/*diagnosis/mortality/pathology ; Adolescent ; Adult ; Aged ; Carcinoma, Ductal, Breast/*diagnosis/mortality/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; SEER Program ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Invasive apocrine adenocarcinoma (AAC) of breast is a rare histopathological subtype of breast carcinomas. We aim to investigate the different characteristics and prognostic outcomes between AAC and invasive ductal carcinoma (IDC) of breast cancer.

RESULTS: AAC patients presented with older ages, more aggressive behaviors, lower ER and PR proportions, higher HER2 amplification rates and less application of breast-conserving therapy and adjuvant chemotherapy compared to IDC patients. Long-term OS and DSS were both worse in ACC patients (p = 0.006, p = 0.012 respectively) than in IDC patients by Kaplan-Meier analysis. However, no significant difference was detected in DSS (p = 0.181) and OS (p = 0.116) between the matched two histological subtypes. Further subgroup analysis indicated that AJCC stage, ER status, PR status and HER2 status may be principal confounders for AAC prognosis.

MATERIALS AND METHODS: With accession to the Surveillance, Epidemiology and End Result (SEER) database, a total of 260,596 patients met the eligibility criteria. Clinicopathological characteristics were compared between groups using Chi-square test. Univariate and multivariate analyses were applied to evaluate the overall survival (OS) and disease-specific survival (DSS). Subgroup analyses summarized the hazard ratio (HR) of AAC versus IDC using a forest plot.

CONCLUSIONS: AAC had unique clinicopathological characteristics and it tended to be a more aggressive type than IDC. However, the worse prognosis was diminished after matching for demographic and clinicopathological factors. Deeper insights into AAC are in need to contribute to individualized and tailored therapy, which thereby may improve clinical management and outcomes.}, } @article {pmid28437469, year = {2017}, author = {Hasler, BS and Spanlang, B and Slater, M}, title = {Virtual race transformation reverses racial in-group bias.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0174965}, pmid = {28437469}, issn = {1932-6203}, mesh = {Adult ; Black or African American/*psychology ; Empathy ; Female ; Humans ; *Interpersonal Relations ; Middle Aged ; Racism/*psychology ; White People/*psychology ; Young Adult ; }, abstract = {People generally show greater preference for members of their own racial group compared to racial out-group members. This type of 'in-group bias' is evident in mimicry behaviors. We tend to automatically mimic the behaviors of in-group members, and this behavior is associated with interpersonal sensitivity and empathy. However, mimicry is reduced when interacting with out-group members. Although race is considered an unchangeable trait, it is possible using embodiment in immersive virtual reality to engender the illusion in people of having a body of a different race. Previous research has used this technique to show that after a short period of embodiment of White people in a Black virtual body their implicit racial bias against Black people diminishes. Here we show that this technique powerfully enhances mimicry. We carried out an experiment with 32 White (Caucasian) female participants. Half were embodied in a White virtual body and the remainder in a Black virtual body. Each interacted in two different sessions with a White and a Black virtual character, in counterbalanced order. The results show that dyads with the same virtual body skin color expressed greater mimicry than those of different color. Importantly, this effect occurred depending on the virtual body's race, not participants' actual racial group. When embodied in a Black virtual body, White participants treat Black as their novel in-group and Whites become their novel out-group. This reversed in-group bias effect was obtained regardless of participants' level of implicit racial bias. We discuss the theoretical and practical implications of this surprising psychological phenomenon.}, } @article {pmid28436838, year = {2018}, author = {Park, K and Chen, W and Chekmareva, MA and Foran, DJ and Desai, JP}, title = {Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.}, journal = {IEEE transactions on bio-medical engineering}, volume = {65}, number = {1}, pages = {96-103}, pmid = {28436838}, issn = {1558-2531}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA161375/CA/NCI NIH HHS/United States ; R01 LM009239/LM/NLM NIH HHS/United States ; }, mesh = {Breast/*physiology ; Breast Neoplasms/*diagnosis/*physiopathology ; Electrodiagnosis/*instrumentation/methods ; Equipment Design ; Female ; Humans ; Micro-Electrical-Mechanical Systems ; }, abstract = {GOAL: This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor.

METHODS: The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range.

CONCLUSION: While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences (0.0039) between the two groups.

SIGNIFICANCE: The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.}, } @article {pmid28434924, year = {2017}, author = {Mori, K and Takeda, M and Kodama, Y and Kiyokawa, H and Yasojima, H and Mizutani, M and Otani, Y and Morikawa, N and Masuda, N and Mano, M}, title = {Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.}, journal = {Human pathology}, volume = {64}, number = {}, pages = {145-155}, doi = {10.1016/j.humpath.2017.04.004}, pmid = {28434924}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/surgery ; Chi-Square Distribution ; Decision Support Techniques ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; ROC Curve ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.}, } @article {pmid28434900, year = {2017}, author = {Hirai, E and Sarukawa, S and Yamamoto, K and Okamoto, M}, title = {Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.}, journal = {Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons}, volume = {75}, number = {7}, pages = {1569.e1-1569.e7}, doi = {10.1016/j.joms.2017.03.035}, pmid = {28434900}, issn = {1531-5053}, mesh = {Aged ; Breast Neoplasms/*etiology ; Female ; Humans ; Muscle Neoplasms/*etiology ; Myocutaneous Flap/*adverse effects ; Neoplasms, Second Primary/*etiology ; Tongue Neoplasms/*surgery ; }, abstract = {Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.}, } @article {pmid28432480, year = {2017}, author = {Song, BI and Kim, HW and Won, KS}, title = {Predictive Value of [18]F-FDG PET/CT for Axillary Lymph Node Metastasis in Invasive Ductal Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {24}, number = {8}, pages = {2174-2181}, doi = {10.1245/s10434-017-5860-0}, pmid = {28432480}, issn = {1534-4681}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multimodal Imaging/*methods ; Neoplasm Invasiveness ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; ROC Curve ; *Radiopharmaceuticals ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by [18]F-fluoro-2-deoxy-D-glucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC).

METHODS: In this study, 128 IDC patients who underwent pretreatment [18]F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed. All the patients were classified as five molecular subtypes. The optimal cutoff values of pSUVmax for all the patients and each molecular subtype for the prediction of ALN metastasis were determined using receiver operating characteristic (ROC) analysis. Furthermore, the prognostic accuracy of ALN metastasis was assessed using c-statistics.

RESULTS: The findings showed ALN metastasis in 52 patients (40.6%). The [18]F-FDG PET/CT procedure had a sensitivity of 48.1% and a specificity of 94.7% for ALN metastasis. In the ROC analysis of pSUVmax for ALN metastasis, the optimal cutoff value was 3.9 for all the patients, 2.8 for the luminal A subtype, 3.3 for the luminal B (human epidermal growth factor receptor 2 [HER2]-negative) subtype, 5.3 for the luminal B (HER2-positive) subtype, 12.7 for the HER2-positive subtype, and 11.5 for the triple-negative subtype. A predictive ALN metastasis model using nodal [18]F-FDG uptake finding gave a c-statistic of 0.714, and a model combination of nodal [18]F-FDG uptake finding with pSUVmax of all the patients gave a c-statistic of 0.736 (P = 0.3926). However, the combination of nodal the [18]F-FDG uptake finding with the pSUVmax of each molecular subtype gave a c-statistic of 0.791 (P = 0.0047).

CONCLUSIONS: Combining the pSUVmax of each molecular subtype with the nodal [18]F-FDG uptake finding can improve the prediction of ALN metastasis in IDC.}, } @article {pmid28431847, year = {2017}, author = {Buehrle, K and Pisano, J and Han, Z and Pettit, NN}, title = {Guideline compliance and clinical outcomes among patients with Staphylococcus aureus bacteremia with infectious diseases consultation in addition to antimicrobial stewardship-directed review.}, journal = {American journal of infection control}, volume = {45}, number = {7}, pages = {713-716}, doi = {10.1016/j.ajic.2017.02.030}, pmid = {28431847}, issn = {1527-3296}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; *Antimicrobial Stewardship ; Bacteremia/*drug therapy/mortality ; *Disease Management ; Female ; *Guideline Adherence ; Humans ; Male ; Middle Aged ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/*drug therapy/mortality ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Previous studies have shown infectious diseases consultation (IDC) for Staphylococcus aureus bacteremia (SAB) improves management and outcomes. The influence of IDC on outcomes for SAB in addition to an antimicrobial stewardship program (ASP) review for adult inpatients with SAB has not been evaluated. The purpose of this study was to investigate the effect of IDC on SAB management with concomitant ASP review and resulting outcomes.

METHODS: Adult inpatients with SAB admitted December 2012-October 2014 were included. The primary end point compared adherence to Infectious Disease Society of America guideline recommendations between patients receiving an IDC versus those not receiving an IDC. We also evaluated adherence to the individual components of the primary end point and clinical outcomes, including time to microbiologic clearance, recurrence of bacteremia, mortality, and length of stay.

RESULTS: This study included 154 patients (115 IDC and 39 non-IDC). Guideline adherence was significantly greater in the IDC group 78% versus 46% in the non-IDC group (P < .001). Significantly more patients in the IDC group had echocardiography (91% vs 67%; P < .001) and follow-up blood cultures (92% vs 64%; P > .001). Mortality was also greater in the non-IDC group (23%) versus 5% for the IDC group (P = .001).

CONCLUSIONS: Patients with SAB receiving an IDC were more likely to receive guideline-congruent management and had significantly reduced mortality. No improvements in antibiotic choice or dosing were observed, likely a result of ASP review.}, } @article {pmid28431489, year = {2017}, author = {Santangelo, G and Siciliano, M and Trojano, L and Femiano, C and Monsurrò, MR and Tedeschi, G and Trojsi, F}, title = {Apathy in amyotrophic lateral sclerosis: insights from Dimensional Apathy Scale.}, journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration}, volume = {18}, number = {5-6}, pages = {434-442}, doi = {10.1080/21678421.2017.1313865}, pmid = {28431489}, issn = {2167-9223}, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*diagnosis/*psychology ; *Apathy ; Female ; Humans ; Male ; Middle Aged ; *Neuropsychological Tests/standards ; Psychiatric Status Rating Scales/standards ; }, abstract = {OBJECTIVES: Apathy is associated with cognitive decline and worse survival in amyotrophic lateral sclerosis (ALS); an accurate evaluation of this aspect is relevant in clinical settings. The aims of this study are to evaluate the prevalence of apathy in a large ALS sample, using published diagnostic criteria, and to explore the psychometric properties, the sensitivity and the specificity of the Dimensional Apathy Scale (DAS) as a screening tool for apathy.

METHODS: One hundred and thirty-one patients underwent clinical interview based on diagnostic criteria for apathy, DAS, Apathy Evaluation Scale, and assessment of depression, global cognitive functioning, and non-verbal intelligence.

RESULTS: According to diagnostic criteria, apathy occurred in 28.2% of the patients. The DAS showed high consistency, convergent, and discriminant validities. Apathetic and non-apathetic patients significantly differed on total DAS and executive and Behavioral/Cognitive Initiation subscales, indicating good criterion validity. Receiver operating characteristics analysis, considering diagnostic criteria for apathy as gold standard, revealed that a score of 26/27 was an optimal cut-off score for the identification of apathy.

CONCLUSIONS: The DAS is a valid screening tool for apathy and its aspects in ALS through limiting the impact of physical disability. Executive and behavioral/cognitive aspects of apathy, rather than emotional aspects, are more frequent in ALS.}, } @article {pmid28431271, year = {2017}, author = {Li, Y and Gao, D and Tu, M and Luo, YZ and Deng, ZH}, title = {Investigation of pathology malpractice claims in China from 2002-2015.}, journal = {Journal of forensic and legal medicine}, volume = {48}, number = {}, pages = {30-34}, doi = {10.1016/j.jflm.2017.04.005}, pmid = {28431271}, issn = {1878-7487}, mesh = {China ; Compensation and Redress/legislation & jurisprudence ; Humans ; Malpractice/*legislation & jurisprudence ; Medical Errors ; Pathology, Clinical/*legislation & jurisprudence ; Retrospective Studies ; }, abstract = {OBJECTIVE: To examine pathology-related medical claims in China and identify the most common errors to result in such claims.

METHOD: A retrospective analysis was performed of 71 forensic evaluation reports carried out in two Chinese institutes of forensic medicine between 2002 and 2015 due to suspicion of medical malpractice. The judicial outcomes of each case were also reviewed when available.

RESULTS: Of 71 cases, 54 cases had judicial outcomes. The most frequently claimed events were false-negative diagnoses of skin cancer, invasive ductal carcinoma of the breast, and osteosarcoma; and false positive diagnoses of uterine cervical squamous cell carcinoma, gastric carcinoma, and soft tissue carcinoma. The most common cause of error (82%, 56 of 68) was pathological misinterpretation. Plaintiffs in most cases (89%, 48 of 54) received compensation.

CONCLUSION: Our data are in agreement with other findings regarding the most frequent medical malpractice allegations related to pathology. Addressing the issues at the root of these claims would lead to a decline in the number of medical errors. Quality assurance programs and good pathologist-clinician communication may decrease the risk of litigation.}, } @article {pmid28430808, year = {2017}, author = {El Guerrab, A and Cayre, A and Kwiatkowski, F and Privat, M and Rossignol, JM and Rossignol, F and Penault-Llorca, F and Bignon, YJ}, title = {Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175960}, pmid = {28430808}, issn = {1932-6203}, mesh = {Breast Neoplasms/genetics/*pathology ; *Cell Hypoxia ; Female ; *Gene Expression ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; }, abstract = {Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression. Gene expression was quantified by RT-qPCR in a retrospective series of 32 patients with invasive ductal carcinoma. Data were analyzed in relation to classical clinicopathological criteria and relapse occurrence. Coordinated overexpression of selected genes was observed in high-grade and HER2+ tumors. Hierarchical cluster analysis of gene expression significantly segregated relapsed patients (p = 0.008, Chi2 test). All genes (except one) were up-regulated and six markers were significantly expressed in tumors from recurrent patients. The expression of this 6-gene set was used to develop a basic algorithm for identifying recurrent patients according to a risk score of relapse. Analysis of Kaplan-Meier relapse-free survival curves allowed the definition of a threshold score of 2 (p = 0.021, Mantel-Haenszel test). The risk of recurrence was increased by 40% in patients with a high score. In addition to classical prognostic factors, we showed that hypoxic markers have potential prognostic value for outcome and late recurrence prediction, leading to improved treatment decision-making for patients with early-stage invasive breast cancer. It will be necessary to validate the clinical relevance of this prognostic approach through independent studies including larger prospective patient cohorts.}, } @article {pmid28430349, year = {2018}, author = {Xu, Y and Lan, S and Zheng, Q}, title = {Prognostic significance of infiltrating immune cell subtypes in invasive ductal carcinoma of the breast.}, journal = {Tumori}, volume = {104}, number = {3}, pages = {196-201}, doi = {10.5301/tj.5000624}, pmid = {28430349}, issn = {2038-2529}, mesh = {B-Lymphocytes/immunology/metabolism/pathology ; Biomarkers/*metabolism ; Breast Neoplasms/*immunology/metabolism/*pathology ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Carcinoma, Ductal/*immunology/metabolism/*pathology ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; T-Lymphocytes, Regulatory/immunology/metabolism/pathology ; }, abstract = {PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis.

MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low).

RESULTS: Kaplan-Meier survival analysis showed (a) for all patients that high tumor-infiltrating CD8+ and CD20+ B lymphocytes, low tumor-infiltrating FOXP3+ regulatory T cells (Tregs), and CD68+ macrophages all increased OS and DFS (p<0.05); (b) for both the 35 ER-negative and 45 lymph-node-negative patients, high CD8+ cytotoxic T lymphocytes (CTLs) increased OS and DFS (p<0.05). Multivariate analysis of OS and DFS showed that for all patients high CD8+ CTLs and low FOXP3+ Tregs were related to good OS and DFS (p<0.05).

CONCLUSION: High numbers of tumor-infiltrating CD8+ and low numbers of FOXP3+ T lymphocytes both could function as potential independent prognostic markers for invasive ductal breast carcinoma.}, } @article {pmid28428649, year = {2017}, author = {França, LKL and Bitencourt, AGV and Paiva, HLS and Silva, CB and Pereira, NP and Paludo, J and Graziano, L and Guatelli, CS and de Souza, JA and Marques, EF}, title = {Role of magnetic resonance imaging in the planning of breast cancer treatment strategies: comparison with conventional imaging techniques.}, journal = {Radiologia brasileira}, volume = {50}, number = {2}, pages = {76-81}, pmid = {28428649}, issn = {0100-3984}, abstract = {OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the planning of breast cancer treatment strategies.

MATERIALS AND METHODS: The study included 160 women diagnosed with breast cancer, who underwent breast MRI for preoperative staging. Using Pearson's correlation coefficient (r), we compared the size of the primary tumor, as determined by MRI, by conventional imaging (mammography and ultrasound), and in the pathological examination (gold standard). The identification of lesions not identified in previous examinations was also evaluated, as was its influence on treatment planning.

RESULTS: The mean age of the patients was 52.2 years (range, 30-81 years), and the most common histological type was invasive ductal carcinoma (in 60.6% of the patients). In terms of the tumor size determined, MRI correlated better with the pathological examination than did mammography (r = 0.872 vs. 0.710) or ultrasound (r = 0.836 vs. 0.704). MRI identified additional lesions in 53 patients (33.1%), including malignant lesions in 20 (12.5%), which led to change in the therapeutic planning in 23 patients (14.4%).

CONCLUSION: Breast MRI proved to be more accurate than conventional imaging in determining the dimensions of the main tumor and was able to identify lesions not identified by other methods evaluated, which altered the therapeutic planning in a significant proportion of cases.}, } @article {pmid28425682, year = {2017}, author = {Degrate, L and Bernasconi, DP and Meroni, P and Garancini, M and Macchini, D and Romano, F and Uggeri, F and Gianotti, L}, title = {Mild acute biliary pancreatitis: the timing of cholecystectomy should not exceed index admission.}, journal = {Minerva chirurgica}, volume = {72}, number = {5}, pages = {383-390}, doi = {10.23736/S0026-4733.17.07356-4}, pmid = {28425682}, issn = {1827-1626}, mesh = {Acute Disease ; Aged ; *Cholecystectomy, Laparoscopic/methods ; Female ; Gallstones/complications/diagnosis/*surgery ; Humans ; Italy ; Male ; Middle Aged ; Pancreatitis/*diagnosis/etiology ; *Patient Selection ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Laparoscopic cholecystectomy (LC) to treat mild biliary acute pancreatitis (MBAP) during index admission is recommended. However, the optimal surgical timing is controversial, considering that patients are actually often discharged from hospital and readmitted for elective cholecystectomy. Moreover, previous studies showed an uneven patients' stratification for pancreatitis severity. The aim of this study was to determine the outcome of patients homogenously categorizedfor MBAP according to the newest pancreatitis classifications, undergoing cholecystectomy with different timing.

METHODS: We retrospectively identified all patients undergoing cholecystectomy from 2008 to 2015 for MBAP, according to the 2012 Revision of the Atlanta Classification and the Determinant-Based Classification of Acute Pancreatitis, and stratified them in two groups: index cholecystectomy (IC) and interval-delayed cholecystectomy (IDC, after at least 4 weeks).

RESULTS: One hundred and three patients were analyzed. IC was performed in 40 patients (38.8%) while IDC in 63 patients (61.2%). The two groups were similar in comorbidities and pancreatitis severity at admission. There were no differences for conversion rate, operation length, total length of hospitalization and overall complication rates. However, IDC patients had a 33.3% rate of re-hospitalization for recurrent biliary-pancreatic events while waiting for the elective procedure and showed a higher rate of acute cholecystitis at histological diagnosis than IC (11.1% vs. 0%, P=0.041).

CONCLUSIONS: Among patients affected by MBAP, homogenously assessed following the new acute pancreatitis severity scores, the performance of cholecystectomy during the index admission is the best treatment option in order to avoid further undesired hospitalizations for recurrent biliary/pancreatic events while waiting for surgery.}, } @article {pmid28424111, year = {2017}, author = {Chung, E and Kapenhas, E and Badia, D and Spektor, M and Gluck, BS and Secola, S}, title = {Management of Recurrent Invasive Ductal Carcinoma in Transrectus Abdominis Myocutaneous Flap and Lymphatic Remodeling to the Contralateral Axilla.}, journal = {The American surgeon}, volume = {83}, number = {4}, pages = {e113-114}, pmid = {28424111}, issn = {1555-9823}, mesh = {Adult ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; Neoplasm Recurrence, Local/*surgery ; Rectus Abdominis/transplantation ; Surgical Flaps ; }, } @article {pmid28423709, year = {2017}, author = {Wu, YP and Chen, SH and Wang, ST and Li, XD and Cai, H and Lin, YZ and Xue, XY and Wei, Y and Zheng, QS and Xu, N}, title = {Prognostic values of clinicopathological characteristics and survival outcomes in prostate infiltrating ductal carcinoma: a population-based study.}, journal = {Oncotarget}, volume = {8}, number = {17}, pages = {29048-29055}, pmid = {28423709}, issn = {1949-2553}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Carcinoma, Acinar Cell/*mortality/*pathology/therapy ; Carcinoma, Ductal/*mortality/*pathology/therapy ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Prostate ; Prostatectomy/statistics & numerical data ; Prostatic Neoplasms/*mortality/*pathology/therapy ; Radiotherapy, Adjuvant/statistics & numerical data ; SEER Program/statistics & numerical data ; Survival Rate ; Young Adult ; }, abstract = {Infiltrating ductal carcinoma (IDC) is a rare histologic subtype of prostate cancer. We investigated the clinicopathological features and prognosis of IDC compared with acinar cell carcinoma (ACC). We identified 3814 men diagnosed with prostate cancer between 2004 to and 2013 in the Surveillance, Epidemiology, and End Results database, including 511 IDC and 3303 ACC cases. Prostate cancer-specific survival (PCSS) was compared using univariate and multivariate Cox proportional hazards models. Generally, IDC occurred in older men (≥ 65 years old) and presented with larger sizes, and higher grades, American Joint Committee on Cancer (AJCC) stages, AJCC T stages, lymph node positive rates and metastasis rates. Men with IDC were less likely to undergo radical prostatectomy, but more likely to be treated with adjuvant radiation than men with ACC. Five-year PCSS rates were significantly worse in IDC. In the multivariate analysis, patients with ACC had a better PCSS than patients with IDC. In conclusion, IDC has unique clinicopathological characteristics and has worse prognosis than ACC. Multivariable Cox regression analysis showed that age over 85 years, higher grade and T stage, and metastasis at diagnosis were independent prognostic factors of worse survival outcomes, whereas radical prostatectomy was an independent prognostic factor of better survival outcomes.}, } @article {pmid28423522, year = {2017}, author = {Qian, L and Gao, X and Huang, H and Lu, S and Cai, Y and Hua, Y and Liu, Y and Zhang, J}, title = {PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.}, journal = {Oncotarget}, volume = {8}, number = {13}, pages = {21444-21453}, pmid = {28423522}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Real-Time Polymerase Chain Reaction ; Tissue Array Analysis ; Trypsin/analysis/*biosynthesis ; Young Adult ; }, abstract = {OBJECTIVE: Serine protease 3 (PRSS3) is an isoform of trypsinogen, and plays an important role in the development of many malignancies. The objective of this study was to determine PRSS3 mRNA and protein expression levels in invasive ductal carcinoma of the breast and normal surrounding tissue samples.

RESULTS: Both PRSS3 mRNA and protein levels were significantly higher in invasive ductal carcinoma of the breast tissues than in normal or benign tissues (all P < 0.05). High PRSS3 protein levels were associated with patients' age, histological grade, Her-2 expression level, ki-67 expression, and the 5.0-year survival rate. These high protein levels are independent prognostic markers in invasive ductal carcinoma of the breast.

MATERIALS AND METHODS: We used real-time quantitative polymerase chain reactions (N = 40) and tissue microarray immunohistochemistry analysis (N = 286) to determine PRSS3 mRNA and protein expression, respectively. PRSS3 protein levels in invasive ductal carcinoma of the breast tissues were correlated with the clinical characteristics of patients with invasive ductal carcinoma of the breast and their 5.0-year survival rate.

CONCLUSIONS: PRSS3 acts as an oncogene in invasive ductal carcinoma of the breast development and progression. This finding implies that detection of PRSS3 expression can be a useful prognosis marker and the targeting of PRSS3 can potentially represent a new strategy for invasive ductal carcinoma of the breast treatment.}, } @article {pmid28422303, year = {2017}, author = {Tang, B and Han, CT and Gan, HL and Zhang, GM and Zhang, CZ and Yang, WY and Shen, Y and Zhu, Y and Ye, DW}, title = {Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.}, journal = {The Prostate}, volume = {77}, number = {9}, pages = {984-989}, doi = {10.1002/pros.23354}, pmid = {28422303}, issn = {1097-0045}, mesh = {Aged ; Biopsy/methods/statistics & numerical data ; *Carcinoma, Ductal/epidemiology/pathology ; China/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Prostate/*pathology ; *Prostatic Neoplasms/epidemiology/pathology ; Risk Factors ; Smoking/*epidemiology ; Statistics as Topic ; }, abstract = {OBJECTIVE: To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men.

PATIENTS AND METHODS: We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence.

RESULTS: A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59).

CONCLUSION: Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa.}, } @article {pmid28422090, year = {2017}, author = {Wu, Q and Ding, X and Li, J and Sun, S and Zhu, S and Wu, J and Liu, Q and Yao, F and Sun, S}, title = {Surgical treatment in Paget's disease with invasive ductal carcinoma: an observational study based on SEER.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {45510}, pmid = {28422090}, issn = {2045-2322}, mesh = {Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Humans ; Paget's Disease, Mammary/complications/*pathology/*surgery ; Prognosis ; Survival Analysis ; Treatment Outcome ; }, abstract = {The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.}, } @article {pmid28421181, year = {2017}, author = {Johnson, JM and Cotzia, P and Fratamico, R and Mikkilineni, L and Chen, J and Colombo, D and Mollaee, M and Whitaker-Menezes, D and Domingo-Vidal, M and Lin, Z and Zhan, T and Tuluc, M and Palazzo, J and Birbe, RC and Martinez-Outschoorn, UE}, title = {MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {5}, number = {}, pages = {27}, pmid = {28421181}, issn = {2296-634X}, support = {K08 CA175193/CA/NCI NIH HHS/United States ; }, abstract = {Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ (p < 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 (p < 0.05). High nuclear grade was associated with higher MCT1 staining (p < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 (p < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status (p < 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using MCT1 inhibitors.}, } @article {pmid28418916, year = {2017}, author = {Tang, SL and Yang, JQ and Du, ZG and Tan, QW and Zhou, YT and Zhang, D and Lv, Q}, title = {Clinicopathologic study of invasive micropapillary carcinoma of the breast.}, journal = {Oncotarget}, volume = {8}, number = {26}, pages = {42455-42465}, pmid = {28418916}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Papillary/mortality/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Analysis ; Young Adult ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma. It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though it is uncertain whether the prognoses of IMPC and IDC differ. In this retrospective study, we compared the clinicopathologic characteristics and survival between 170 female patients with IMPC (pure or mixed with IDC) and 728 with pure IDC. The IMPC patients had higher clinical stages and histologic grades, higher incidences of lymphovascular invasion and axillary lymph node extracapsular extension, and a higher degree of lymph node involvement than IDC patients. Moreover, IMPC was associated with increases in estrogen receptor (ER) and progesterone receptor (PR) positivity and HER-2 overexpression. Although locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) were poorer in IMPC patients than IDC patients, overall survival and distant metastasis survival did not differ between the two groups. Multivariate analysis revealed that IMPC was an independent prognostic factor for LRRFS in breast cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment decisions, patients with breast carcinoma be tested for the presence of this specific subtype.}, } @article {pmid28418027, year = {2017}, author = {Cruz-Roa, A and Gilmore, H and Basavanhally, A and Feldman, M and Ganesan, S and Shih, NNC and Tomaszewski, J and González, FA and Madabhushi, A}, title = {Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {46450}, pmid = {28418027}, issn = {2045-2322}, support = {R01 CA202752/CA/NCI NIH HHS/United States ; R21 CA167811/CA/NCI NIH HHS/United States ; R43 EB015199/EB/NIBIB NIH HHS/United States ; C06 RR012463/RR/NCRR NIH HHS/United States ; U24 CA199374/CA/NCI NIH HHS/United States ; R21 CA179327/CA/NCI NIH HHS/United States ; R21 CA195152/CA/NCI NIH HHS/United States ; R01 DK098503/DK/NIDDK NIH HHS/United States ; R01 CA208236/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Algorithms ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Deep Learning ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Invasiveness ; Tumor Burden ; Young Adult ; }, abstract = {With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast cancer by a pathologist is critical for patient management for tumor staging and assessing treatment response. However, this process is tedious and subject to inter- and intra-reader variability. For computerized methods to be useful as decision support tools, they need to be resilient to data acquired from different sources, different staining and cutting protocols and different scanners. The objective of this study was to evaluate the accuracy and robustness of a deep learning-based method to automatically identify the extent of invasive tumor on digitized images. Here, we present a new method that employs a convolutional neural network for detecting presence of invasive tumor on whole slide images. Our approach involves training the classifier on nearly 400 exemplars from multiple different sites, and scanners, and then independently validating on almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice coefficient of 75.86%, a positive predictive value of 71.62% and a negative predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to manually annotated regions of invasive ductal carcinoma.}, } @article {pmid28416734, year = {2017}, author = {Coulson, R and Liew, SH and Connelly, AA and Yee, NS and Deb, S and Kumar, B and Vargas, AC and O'Toole, SA and Parslow, AC and Poh, A and Putoczki, T and Morrow, RJ and Alorro, M and Lazarus, KA and Yeap, EFW and Walton, KL and Harrison, CA and Hannan, NJ and George, AJ and Clyne, CD and Ernst, M and Allen, AM and Chand, AL}, title = {The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma.}, journal = {Oncotarget}, volume = {8}, number = {12}, pages = {18640-18656}, pmid = {28416734}, issn = {1949-2553}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Animals ; Biopsy ; Breast Neoplasms/*pathology ; Carcinogenesis/metabolism ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemically induced/*drug therapy/immunology/pathology ; Cell Proliferation/drug effects ; *Disease Progression ; Female ; Humans ; Immunohistochemistry ; Interleukin-6/metabolism ; Losartan/*therapeutic use ; Mammary Neoplasms, Experimental/chemically induced/*drug therapy/immunology/pathology ; Medroxyprogesterone Acetate/toxicity ; Mice ; Neoplasm Invasiveness ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 1/*metabolism ; Renin-Angiotensin System/drug effects ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Tumor Burden/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation ; }, abstract = {Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no evidence, so far, of the functional contribution of AT1R to breast tumorigenesis. We explored the potential therapeutic benefit of ARB in a carcinogen-induced mouse model of breast cancer and clarified the mechanisms associated with its success.Mammary tumors were induced with 7,12-dimethylbenz[α]antracene (DMBA) and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of the ARB, Losartan treatment assessed in a preventative setting (n = 15 per group). Tumor histopathology was characterised by immunohistochemistry, real-time qPCR to detect gene expression signatures, and tumor cytokine levels measured with quantitative bioplex assays. AT1R was detected with radiolabelled ligand binding assays in fresh frozen tumor samples.We showed that therapeutic inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor burden; and no mammary tumor incidence in 20% of animals. We observed a significant reduction in tumor progression from DCIS to invasive cancer with Losartan treatment. This was associated with reduced tumor cell proliferation and a significant reduction in IL-6, pSTAT3 and TNFα levels. Analysis of tumor immune cell infiltrates, however, demonstrated no significant differences in the recruitment of lymphocytes or tumour-associated macrophages in Losartan or vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled ligand binding assays in human breast cancer biopsies showed high AT1R levels in 30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA database identified that high AT1R expression to be associated with luminal breast cancer subtype.Our in vivo data and analysis of human invasive ductal carcinoma samples identify the AT1R is a potential therapeutic target in breast cancer, with the availability of a range of well-tolerated inhibitors currently used in clinics. We describe a novel signalling pathway critical in breast tumorigenesis, that may provide new therapeutic avenues to complement current treatments.}, } @article {pmid28415815, year = {2017}, author = {Cen, D and Xu, L and Zhang, S and Zhou, S and Huang, Y and Chen, Z and Li, N and Wang, Y and Wang, Q}, title = {BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast cancer.}, journal = {Oncotarget}, volume = {8}, number = {18}, pages = {30190-30198}, pmid = {28415815}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor ; Breast Neoplasms/*diagnostic imaging/*pathology ; Calcinosis/*diagnostic imaging/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Prognosis ; ROC Curve ; }, abstract = {PURPOSE: To determine whether the clinicopathological parameters and Breast Imaging Reporting and Data System (BI-RADS) 3-5 microcalcifications differed between lymph node positive (LN (+)) and lymph node negative (LN (-)) invasive ductal carcinoma (IDC).

RESULTS: For microcalcification-associated breast cancers, seven selected features (age, tumor size, Ki-67 status, lymphovascular invasion, calcification range, calcification diameter and calcification density) were significantly associated with LN status (all P < 0.05). Multivariate logistic regression analysis found that three risk factors (age: older vs. younger OR: 0.973 P = 0.006, tumor size: larger vs. smaller OR: 1.671, P < 0.001 and calcification density: calcifications > 20/cm2 vs. calcifications ≤ 20/cm2 OR: 1.698, P < 0.001) were significant independent predictors. This model had an area under the receiver operating characteristic curve (AUC) of 0.701. The nodal staging (N0 and N1 χ2 = 5.701, P = 0.017; N0 and N2 χ2 = 6.614, P = 0.013) was significantly positively associated with calcification density. The luminal B subtype had the highest risk of LN metastasis. Multivariate analysis demonstrated that calcification > 2 cm in range (OR: 2.209) and larger tumor size (OR: 1.882) were independently predictive of LN metastasis in the luminal B subtype (AUC = 0.667).

MATERIALS AND METHODS: Mammographic images of 419 female breast cancer patients were included. Associations between the risk factors and LN status were evaluated using a Chi-square test, ANOVA and binary logistic regression analysis.

CONCLUSIONS: This study found that age, tumor size and calcifications density can be conveniently used to facilitate the preoperative prediction of LN metastasis. The luminal B subtype has the highest risk of LN metastasis among the microcalcification-associated breast cancers.}, } @article {pmid28414329, year = {2017}, author = {Fischer, K and Ruiz, HH and Jhun, K and Finan, B and Oberlin, DJ and van der Heide, V and Kalinovich, AV and Petrovic, N and Wolf, Y and Clemmensen, C and Shin, AC and Divanovic, S and Brombacher, F and Glasmacher, E and Keipert, S and Jastroch, M and Nagler, J and Schramm, KW and Medrikova, D and Collden, G and Woods, SC and Herzig, S and Homann, D and Jung, S and Nedergaard, J and Cannon, B and Tschöp, MH and Müller, TD and Buettner, C}, title = {Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.}, journal = {Nature medicine}, volume = {23}, number = {5}, pages = {623-630}, pmid = {28414329}, issn = {1546-170X}, support = {R01 DK017844/DK/NIDDK NIH HHS/United States ; R03 DK082724/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 AI093637/AI/NIAID NIH HHS/United States ; R01 DK099222/DK/NIDDK NIH HHS/United States ; R37 DK017844/DK/NIDDK NIH HHS/United States ; R56 DK083658/DK/NIDDK NIH HHS/United States ; 340345/ERC_/European Research Council/International ; R01 AA023416/AA/NIAAA NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Adipocytes/drug effects/*metabolism ; Adipose Tissue/drug effects/*metabolism ; Adipose Tissue, Brown/drug effects/metabolism ; Adipose Tissue, White/drug effects/metabolism ; Animals ; Blotting, Western ; Body Composition/immunology ; Catecholamines/metabolism ; Cell Differentiation ; Culture Media, Conditioned ; Energy Metabolism/genetics ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Interleukin-4/immunology/pharmacology ; Macrophages/drug effects/*immunology ; Mice ; Mice, Knockout ; Norepinephrine/*metabolism ; Receptors, Adrenergic, beta-3/*metabolism ; Receptors, Cell Surface/genetics ; Thermogenesis/genetics/*immunology ; Tyrosine 3-Monooxygenase/*genetics ; Uncoupling Protein 1/genetics ; }, abstract = {Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1[-/-] and interleukin-4 receptor-α double-negative (Il4ra[-/-]) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.}, } @article {pmid28414115, year = {2017}, author = {Yu, J and Elmore, LC and Cyr, AE and Aft, RL and Gillanders, WE and Margenthaler, JA}, title = {Cost Analysis of a Surgical Consensus Guideline in Breast-Conserving Surgery.}, journal = {Journal of the American College of Surgeons}, volume = {225}, number = {2}, pages = {294-301}, pmid = {28414115}, issn = {1879-1190}, support = {T32 CA009621/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*economics/*surgery ; Cohort Studies ; Consensus Development Conferences as Topic ; *Costs and Cost Analysis ; Female ; Humans ; Mastectomy, Segmental/*economics/*standards ; Middle Aged ; Practice Guidelines as Topic ; Retrospective Studies ; }, abstract = {BACKGROUND: The Society of Surgical Oncology and American Society of Radiation Oncology consensus statement was the first professional guideline in breast oncology to declare "no ink on tumor" as a negative margin in patients with stages I/II breast cancer undergoing breast-conservation therapy. We sought to analyze the financial impact of this guideline at our institution using a historic cohort.

STUDY DESIGN: We identified women undergoing re-excision after breast-conserving surgery for invasive breast cancer from 2010 through 2013 using a prospectively maintained institutional database. Clinical and billing data were extracted from the medical record and from administrative resources using CPT codes. Descriptive statistics were used in data analysis.

RESULTS: Of 254 women in the study population, 238 (93.7%) had stage I/II disease and 182 (71.7%) had invasive disease with ductal carcinoma in situ. A subcohort of 83 patients (32.7%) who underwent breast-conservation therapy for stage I/II disease without neoadjuvant chemotherapy had negative margins after the index procedure, per the Society of Surgical Oncology and American Society of Radiation Oncology guideline. The majority had invasive ductal carcinoma (n = 70 [84.3%]) and had invasive disease (n = 45 [54.2%]), and/or ductal carcinoma in situ (n = 49 [59.0%]) within 1 mm of the specimen margin. Seventy-nine patients underwent 1 re-excision and 4 patients underwent 2 re-excisions, accounting for 81 hours of operative time. Considering facility fees and primary surgeon billing alone, the overall estimated cost reduction would have been $195,919, or $2,360 per affected patient, under the guideline recommendations.

CONCLUSIONS: Implementation of the Society of Surgical Oncology and American Society of Radiation Oncology consensus guideline holds great potential to optimize resource use. Application of the guideline to a retrospective cohort at our institution would have decreased the overall re-excision rate by 5.6% and reduced costs by nearly $200,000. Additional analysis of patient outcomes and margin assessment methods is needed to define the long-term impact on surgical practice.}, } @article {pmid28413435, year = {2017}, author = {San, TH and Fujisawa, M and Fushimi, S and Yoshimura, T and Ohara, T and Soe, L and Min, NW and Kyaw, O and Yang, X and Matsukawa, A}, title = {Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from Myanmar.}, journal = {Infectious agents and cancer}, volume = {12}, number = {}, pages = {20}, pmid = {28413435}, issn = {1750-9378}, abstract = {BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown.

METHODS: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed.

RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1, M0).

CONCLUSIONS: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.}, } @article {pmid28412522, year = {2017}, author = {Amri, EZ and Scheideler, M}, title = {Small non coding RNAs in adipocyte biology and obesity.}, journal = {Molecular and cellular endocrinology}, volume = {456}, number = {}, pages = {87-94}, doi = {10.1016/j.mce.2017.04.009}, pmid = {28412522}, issn = {1872-8057}, mesh = {Adipocytes, Brown/*metabolism/pathology ; Adipocytes, White/*metabolism/pathology ; Adipogenesis/genetics ; Adipose Tissue/metabolism/pathology ; Animals ; Biomarkers/metabolism ; Energy Intake/genetics ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/diagnosis/*genetics/metabolism/pathology ; RNA, Small Nucleolar/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; }, abstract = {Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs. ncRNAs regulate gene expression at the transcriptional and post-transcriptional level. Numerous studies described the involvement of ncRNAs in the pathogenesis of many diseases including obesity and associated metabolic disorders. ncRNAs represent potential diagnostic biomarkers and promising therapeutic targets. In this review, we focused on small ncRNAs involved in the formation and function of adipocytes and obesity.}, } @article {pmid28410206, year = {2017}, author = {Fu, S and Cheng, J and Wei, C and Yang, L and Xiao, X and Zhang, D and Stewart, MD and Fu, J}, title = {Development of diagnostic SCAR markers for genomic DNA amplifications in breast carcinoma by DNA cloning of high-GC RAMP-PCR fragments.}, journal = {Oncotarget}, volume = {8}, number = {27}, pages = {43866-43877}, pmid = {28410206}, issn = {1949-2553}, mesh = {Adult ; Aged ; Base Composition ; Base Sequence ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/genetics ; Cloning, Molecular ; DNA Primers ; Dipeptidases/genetics ; Female ; GPI-Linked Proteins/genetics ; *Gene Amplification ; *Genomics/methods ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger/genetics ; Random Amplified Polymorphic DNA Technique ; Sequence Analysis, DNA ; }, abstract = {Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants. In this study, we applied this effective DNA marker technique to generate genetic fingerprints that detect genomic alterations in human breast cancer tissues and then developed sequence-characterized amplified region (SCAR) markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations in the expression of these genes could contribute to cancer progression. Screening of breast cancer cell lines showed that the mRNA expression levels for the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A, but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal carcinoma specimens was significantly higher than that of the adjacent normal tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in measuring genomic DNA amplifications, deletion or copy number variations. Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers for breast cancer carcinomas.}, } @article {pmid28409377, year = {2017}, author = {Ome, Y and Hashida, K and Yokota, M and Nagahisa, Y and Michio, O and Kawamoto, K}, title = {Laparoscopic radical antegrade modular pancreatosplenectomy for left-sided pancreatic cancer using the ligament of Treitz approach.}, journal = {Surgical endoscopy}, volume = {31}, number = {11}, pages = {4836-4837}, pmid = {28409377}, issn = {1432-2218}, mesh = {Aged ; Humans ; Laparoscopy/methods ; Ligaments/surgery ; Male ; Pancreas/surgery ; Pancreatectomy/methods ; Pancreatic Neoplasms/*surgery ; Splenectomy/methods ; Video Recording ; }, abstract = {BACKGROUND: Laparoscopic distal pancreatectomy (Lap-DP) for benign lesions or those with low malignant potential has been proven safe and effective, and its performance is now widespread [1-3]. Lap-DP for left-sided pancreatic cancer (PC) is also being increasingly performed. According to some reports, Lap-DP has superior short-term outcomes (blood loss, postoperative hospital stay) and comparable oncological outcomes and overall survival with those of open distal pancreatectomy (Op-DP) [4-6]. PC has highly malignant potential; thus, complete resection and sufficient regional lymphadenectomy with tumor-free margins are very important. Radical antegrade modular pancreatosplenectomy (RAMPS) is an accepted standard Op-DP technique for PC and is reportedly useful for achieving R0 resection and radical lymphadenectomy [7-10]. However, laparoscopic RAMPS (Lap-RAMPS) is not yet popular because of its technical difficulty and lack of adequate evidence. Few reports have described the detailed surgical technique of Lap-RAMPS [11-13]. We employ Lap-RAMPS using the ligament of Treitz approach with the benefit of a laparoscopic view and herein describe the usability of this laparoscopic procedure with a video.

METHODS: Our indication for Lap-RAMPS is left-sided PC located ≥1 cm away from the origin of the splenic artery (SPA) without invasion of the superior mesenteric artery (SMA), celiac artery (CA), common hepatic artery (CHA), or portal vein (PV). We apply either anterior or posterior RAMPS to achieve tumor-free margins. Therefore, the left adrenal gland and the nerve plexus around the SMA and CA are resected depending on the extent of the cancer. Three patients underwent Lap-RAMPS for left-sided PC using the ligament of Treitz approach from April to December 2016. This video shows our Lap-RAMPS procedure performed in a 67-year-old man with pancreatic body cancer who was being followed up for autoimmune pancreatitis. The tumor was suspected to have invaded the SPA, splenic vein, and retroperitoneum but was not close to the SMA, CA, CHA, or PV. The patient was put in the supine position with his legs opened, and the operation was performed using five trocars. Early in the operation, we incised the retroperitoneum just beside the ligament of Treitz, and the inferior vena cava and left renal vein (LRV) were exposed with resection of Gerota's fascia under a good laparoscopic view. The left adrenal gland was resected in this case to obtain sufficient tumor-free margins. The origin of the SMA was easily identified above the LRV. The most posterior dissection was carried out early in the operation, making it easy and safe to determine the resected margin and enabling curative resection with sufficient regional lymphadenectomy. After division of the pancreas with a linear stapler, the lymph nodes around the SMA and CA were safely removed.

RESULTS: The operative time was 358 min, and the estimated blood loss was 1 ml. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. Pathological examination revealed invasive ductal carcinoma (stage III, T3N1M0 according to the 7th edition of the Union for International Cancer Control system) with tumor-free margins. In all three patients, the median operative time and blood loss were 358 (328-451) min and minimal (minimal to 1 ml). One patient underwent anterior RAMPS and the other two patients, including the case mentioned above, underwent posterior RAMPS. One patient developed a grade B pancreatic fistula according to the International Study Group for Pancreatic Fistula (ISGPF) classification, but he recovered promptly with conservative treatment. No life-threatening complications occurred. The median postoperative hospital stay was 14 (10-16) days.

CONCLUSIONS: Lap-RAMPS using the ligament of Treitz approach is feasible and extremely helpful in performing minimally invasive, curative resection for well-selected left-sided PC.}, } @article {pmid28409065, year = {2017}, author = {Chambers, I and Rahal, AK and Reddy, PS and Kallail, KJ}, title = {Malignant Clear Cell Hidradenoma of the Breast.}, journal = {Cureus}, volume = {9}, number = {3}, pages = {e1064}, pmid = {28409065}, issn = {2168-8184}, abstract = {A 58-year-old female had a mass in the right breast palpable beneath the areola. A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with a subsequent ultrasound. The patient underwent a core needle biopsy which was initially reported as a moderately differentiated invasive ductal carcinoma. Immunohistochemical analysis revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), mammaglobin, and gross cystic disease fluid protein 15 (GCDFP-15). A wide local excision of the mass was performed. The pathology report stated the tumor had an infiltrative growth pattern with a desmoplastic stromal response with enhanced epithelial atypia consistent with malignant transformation of a nodular clear cell hidradenoma. Clear cell hidradenoma is a very rare tumor originating from the sweat gland and has a propensity for the face and extremities. The malignant variant of this tumor is extremely rare and has been reported to originate from the breast in few cases. This case represents the difficulty in diagnosing this tumor along with the radiographic and histologic features that can distinguish this malignancy from other entities.}, } @article {pmid28405214, year = {2017}, author = {Naik, HS and Zhang, J and Lofquist, A and Assefa, T and Sarkar, S and Ackerman, D and Singh, A and Singh, AK and Ganapathysubramanian, B}, title = {A real-time phenotyping framework using machine learning for plant stress severity rating in soybean.}, journal = {Plant methods}, volume = {13}, number = {}, pages = {23}, pmid = {28405214}, issn = {1746-4811}, abstract = {BACKGROUND: Phenotyping is a critical component of plant research. Accurate and precise trait collection, when integrated with genetic tools, can greatly accelerate the rate of genetic gain in crop improvement. However, efficient and automatic phenotyping of traits across large populations is a challenge; which is further exacerbated by the necessity of sampling multiple environments and growing replicated trials. A promising approach is to leverage current advances in imaging technology, data analytics and machine learning to enable automated and fast phenotyping and subsequent decision support. In this context, the workflow for phenotyping (image capture → data storage and curation → trait extraction → machine learning/classification → models/apps for decision support) has to be carefully designed and efficiently executed to minimize resource usage and maximize utility. We illustrate such an end-to-end phenotyping workflow for the case of plant stress severity phenotyping in soybean, with a specific focus on the rapid and automatic assessment of iron deficiency chlorosis (IDC) severity on thousands of field plots. We showcase this analytics framework by extracting IDC features from a set of ~4500 unique canopies representing a diverse germplasm base that have different levels of IDC, and subsequently training a variety of classification models to predict plant stress severity. The best classifier is then deployed as a smartphone app for rapid and real time severity rating in the field.

RESULTS: We investigated 10 different classification approaches, with the best classifier being a hierarchical classifier with a mean per-class accuracy of ~96%. We construct a phenotypically meaningful 'population canopy graph', connecting the automatically extracted canopy trait features with plant stress severity rating. We incorporated this image capture → image processing → classification workflow into a smartphone app that enables automated real-time evaluation of IDC scores using digital images of the canopy.

CONCLUSION: We expect this high-throughput framework to help increase the rate of genetic gain by providing a robust extendable framework for other abiotic and biotic stresses. We further envision this workflow embedded onto a high throughput phenotyping ground vehicle and unmanned aerial system that will allow real-time, automated stress trait detection and quantification for plant research, breeding and stress scouting applications.}, } @article {pmid28403836, year = {2017}, author = {Fu, G and Wang, G and Dai, X}, title = {An adaptive threshold determination method of feature screening for genomic selection.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {212}, pmid = {28403836}, issn = {1471-2105}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/genetics ; Computer Simulation ; Genome, Plant ; Genome-Wide Association Study ; Genomics ; *Models, Genetic ; Phenotype ; Plant Breeding ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Although the dimension of the entire genome can be extremely large, only a parsimonious set of influential SNPs are correlated with a particular complex trait and are important to the prediction of the trait. Efficiently and accurately selecting these influential SNPs from millions of candidates is in high demand, but poses challenges. We propose a backward elimination iterative distance correlation (BE-IDC) procedure to select the smallest subset of SNPs that guarantees sufficient prediction accuracy, while also solving the unclear threshold issue for traditional feature screening approaches.

RESULTS: Verified through six simulations, the adaptive threshold estimated by the BE-IDC performed uniformly better than fixed threshold methods that have been used in the current literature. We also applied BE-IDC to an Arabidopsis thaliana genome-wide data. Out of 216,130 SNPs, BE-IDC selected four influential SNPs, and confirmed the same FRIGIDA gene that was reported by two other traditional methods.

CONCLUSIONS: BE-IDC accommodates both the prediction accuracy and the computational speed that are highly demanded in the genomic selection.}, } @article {pmid28401771, year = {2018}, author = {Brück, N and Koskivuo, I and Boström, P and Saunavaara, J and Aaltonen, R and Parkkola, R}, title = {Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.}, journal = {Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society}, volume = {107}, number = {1}, pages = {14-22}, doi = {10.1177/1457496917701669}, pmid = {28401771}, issn = {1799-7267}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/mortality/*surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/mortality/*surgery ; Disease-Free Survival ; Female ; Finland ; Hospitals, University ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/pathology/surgery ; Preoperative Care/methods ; Prognosis ; Prospective Studies ; Risk Assessment ; Statistics, Nonparametric ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND AND AIMS: Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma.

MATERIAL AND METHODS: A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms.

RESULTS: In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group (p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group (p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group (p < 0.001).

CONCLUSION: Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.}, } @article {pmid28401339, year = {2017}, author = {Miyata, M and Aoki, T and Shimajiri, S and Matsuyama, A and Kinoshita, S and Fujii, M and Katsuki, T and Inoue, Y and Nagata, Y and Tashima, Y and Korogi, Y}, title = {Evaluation of the R2* value in invasive ductal carcinoma with respect to hypoxic-related prognostic factors using iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL).}, journal = {European radiology}, volume = {27}, number = {10}, pages = {4316-4323}, pmid = {28401339}, issn = {1432-1084}, mesh = {Adipose Tissue ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/blood supply/*diagnostic imaging/pathology ; Carcinoma, Ductal/blood supply/*diagnostic imaging/pathology ; Female ; Fibrosis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/analysis ; Least-Squares Analysis ; Magnetic Resonance Imaging/*methods ; Prognosis ; Retrospective Studies ; Water ; }, abstract = {OBJECTIVE: To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma.

METHODS: Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α.

RESULTS: FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001).

CONCLUSION: Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma.

KEY POINTS: • R2* value obtained by IDEAL correlates with the overexpression of HIF-1α. • R2* value obtained by IDEAL is associated with fibrotic focus. • R2* quantification may be useful in predicting hypoxia of breast carcinoma.}, } @article {pmid28400203, year = {2017}, author = {Desmedt, C and Zoppoli, G and Sotiriou, C and Salgado, R}, title = {Transcriptomic and genomic features of invasive lobular breast cancer.}, journal = {Seminars in cancer biology}, volume = {44}, number = {}, pages = {98-105}, doi = {10.1016/j.semcancer.2017.03.007}, pmid = {28400203}, issn = {1096-3650}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Genome, Human ; Genomics ; Humans ; Neoplasm Invasiveness/*genetics/pathology ; Prognosis ; Transcriptome/*genetics ; }, abstract = {Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance.}, } @article {pmid28396662, year = {2017}, author = {Mbongue, JC and Nieves, HA and Torrez, TW and Langridge, WH}, title = {The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {327}, pmid = {28396662}, issn = {1664-3224}, support = {P20 MD006988/MD/NIMHD NIH HHS/United States ; S10 RR027643/RR/NCRR NIH HHS/United States ; }, abstract = {Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens. During activation, the iDCs become mature. Maturation begins when the DCs cease taking up antigens and begin to migrate from their location in peripheral tissues to adjacent lymph nodes or the spleen where during their continued maturation the DCs present stored antigens on surface MHCII receptor molecules to naive Th0 cells. During antigen presentation, the DCs upregulate the biosynthesis of costimulatory receptor molecules CD86, CD80, CD83, and CD40 on their plasma membrane. These activated DC receptor molecules bind cognate CD28 receptors presented on the Th0 cell membrane, which triggers DC secretion of IL-12 or IL-10 cytokines resulting in T cell differentiation into pro- or anti-inflammatory T cell subsets. Although basic concepts involved in the process of iDC activation and guidance of Th0 cell differentiation have been previously documented, they are poorly defined. In this review, we detail what is known about the process of DC maturation and its role in the induction of insulin-dependent diabetes mellitus autoimmunity.}, } @article {pmid28395915, year = {2017}, author = {Abel, S and Renz, P and Trombetta, M and Cowher, M and Day Werts, E and Julian, TB and Wegner, R}, title = {Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.}, journal = {Practical radiation oncology}, volume = {7}, number = {3}, pages = {167-172}, doi = {10.1016/j.prro.2016.10.018}, pmid = {28395915}, issn = {1879-8519}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Radiodermatitis/*etiology ; Radiotherapy/*adverse effects/*methods ; Retrospective Studies ; Thoracic Wall ; Treatment Failure ; }, abstract = {PURPOSE: Postmastectomy chest wall radiation therapy has historically used bolus to increase dose at the skin surface. Despite the theoretical benefits of bolus, the clinical implications of locoregional tumor control, cosmesis, and the incidence of radiodermatitis are less well characterized. We hypothesized that treatment in the presence or absence of bolus results in equivalent chest wall recurrence rates, but its presence results in more severe acute dermatologic toxicity.

METHODS AND MATERIALS: Locally advanced breast cancer patients undergoing chest wall radiation therapy were retrospectively reviewed from 2005 to 2015 (n = 106; 53 with bolus, 53 without). Outcomes including local failure, acute skin toxicity, and treatment interruptions were recorded. Median age was 59 years (range, 28-91) and median follow-up was 34 months. Histology was invasive ductal carcinoma (73%), invasive lobular carcinoma (20%), inflammatory (6%), and neuroendocrine (1%). Fifty-nine percent were T3/T4 primary tumors and 29.2% had clinical/pathologic skin involvement. Node-positive patients accounted for 80.2%. Chemotherapy was administered in 84.0%. All patients had 3-dimensional conformal radiation therapy and received a median dose of 61Gy (range, 50-63 Gy).

RESULTS: Local failure was 6.6% (n = 7) overall, with 4 failures in the bolus group and 3 in the no bolus group. No pathological factors were associated with local failure. Acute grade 2 and 3 skin toxicities (37 vs 22) and treatment interruptions (20 vs 3) were more common in the bolus group (P < .05). Mean treatment interruption (14.5 vs 5 days) was longer for patients receiving bolus. Patients undergoing treatment interruption were more likely to fail locally than patients not requiring a treatment interruption (17.4% vs 3.6%, P = .0322).

CONCLUSIONS: Bolus omission in adjuvant chest wall radiation therapy may be a reasonable approach to avoid acute skin toxicity and treatment interruptions while preserving local control; however, further study will be needed to reach a definitive conclusion.}, } @article {pmid28391968, year = {2017}, author = {Barzilay, S and Brunstein Klomek, A and Apter, A and Carli, V and Wasserman, C and Hadlaczky, G and Hoven, CW and Sarchiapone, M and Balazs, J and Kereszteny, A and Brunner, R and Kaess, M and Bobes, J and Saiz, P and Cosman, D and Haring, C and Banzer, R and Corcoran, P and Kahn, JP and Postuvan, V and Podlogar, T and Sisask, M and Varnik, A and Wasserman, D}, title = {Bullying Victimization and Suicide Ideation and Behavior Among Adolescents in Europe: A 10-Country Study.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {61}, number = {2}, pages = {179-186}, doi = {10.1016/j.jadohealth.2017.02.002}, pmid = {28391968}, issn = {1879-1972}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Bullying/*statistics & numerical data ; Crime Victims/*statistics & numerical data ; Europe ; Female ; Humans ; Male ; Prevalence ; Protective Factors ; Self Report ; Suicide/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {PURPOSE: To examine risk and protective factors moderating the associations between three types of bullying victimization (physical, verbal, and relational bullying) with suicide ideation/attempts in a large representative sample of European adolescents.

METHODS: We analyzed cross-sectional data on 11,110 students (mean age = 14.9, standard deviation = .89) recruited from 168 schools in 10 European Union countries involved in the Saving and Empowering Young Lives in Europe study. A self-report questionnaire was used to measure victimization types, depression, anxiety, parental and peer support, and suicide ideation and attempts. For each outcome, we applied hierarchical nonlinear models controlling for sociodemographics.

RESULTS: Prevalence of victimization was 9.4% physical, 36.1% verbal, and 33.0% relational. Boys were more likely to be physically and verbally victimized, whereas girls were more prone to relational victimization. Physical victimization was associated with suicide ideation, and relational victimization was associated with suicide attempts. Other associations between victimization and suicidality (ideation/attempts) were identified through analysis of interactions with additional risk and protective factors. Specifically, verbal victimization was associated with suicide ideation among adolescents with depression who perceived low parental support. Similarly, low peer support increased the associations between verbal victimization and suicide ideation. Verbal victimization was associated with suicide attempts among adolescents with anxiety who perceived low parental support.

CONCLUSIONS: Findings support the development of prevention strategies for adolescent victims of bullying who may be at elevated risk for suicide ideation/behavior, by taking into account gender, the type of bullying, symptomatology, and availability of interpersonal support.}, } @article {pmid28391236, year = {2017}, author = {Weis, S and Hagel, S and Schmitz, RP and Scherag, A and Brunkhorst, FM and Forstner, C and Löffler, B and Pletz, MW}, title = {Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.}, journal = {BMJ open}, volume = {7}, number = {4}, pages = {e013976}, pmid = {28391236}, issn = {2044-6055}, mesh = {Administration, Intravenous ; Anti-Bacterial Agents/therapeutic use ; Clinical Protocols ; Cluster Analysis ; *Counseling/methods ; Cross-Over Studies ; Germany/epidemiology ; Humans ; Patient Education as Topic ; Program Evaluation ; Quality Assurance, Health Care ; Referral and Consultation ; *Staphylococcal Infections/drug therapy/epidemiology/prevention & control ; Staphylococcus aureus/*drug effects ; Telephone ; }, abstract = {INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question.

METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC.

ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media.

TRIAL REGISTRATION NUMBER: DRKS00010135.}, } @article {pmid28389975, year = {2017}, author = {Santangelo, G and D'Iorio, A and Piscopo, F and Cuoco, S and Longo, K and Amboni, M and Baiano, C and Tafuri, D and Pellecchia, MT and Barone, P and Vitale, C}, title = {Assessment of apathy minimising the effect of motor dysfunctions in Parkinson's disease: a validation study of the dimensional apathy scale.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {26}, number = {9}, pages = {2533-2540}, pmid = {28389975}, issn = {1573-2649}, mesh = {Aged ; Apathy ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/pathology/*psychology ; Psychiatric Status Rating Scales ; Psychometrics/*methods ; Quality of Life/*psychology ; }, abstract = {PURPOSE: Apathy is associated with motor symptoms in Parkinson's disease (PD); therefore, its evaluation could be influenced by motor disability. The Dimensional Apathy Scale (DAS) evaluates apathy excluding confounding effects of motor symptoms. The present study had three major aims: (a) to explore the psychometric properties of the DAS in non-demented PD patients; (b) to determine an optimal cut-off score of the DAS to identify apathetic PD patients; and (c) to determine a specific apathy profile in PD patients as compared to healthy controls (HC).

METHODS: One hundred and seven PD patients and 100 HC completed the DAS. To explore convergent and divergent validity of the DAS in PD, patients underwent the Apathy Evaluation Scale and tools for assessing depressive symptoms, anxiety and cognition. Clinical aspects were recorded. Receiver operating characteristic curve analyses were carried out to estimate the optimal cut-off score to identify clinically significant apathy.

RESULTS: The DAS scores showed high internal consistency and good evidence for convergent and discriminant validity. Maximum discrimination between apathetic and non-apathetic patients was obtained with a cut-off score of 28.5 (total score range: 0-72 with higher score indicating more severe apathy). Comparison between PD and HC groups revealed significant differences on total DAS, behavioural/cognitive initiation and emotional subscales.

CONCLUSIONS: The DAS is a valid and reliable tool to assess multidimensional apathy in PD, independently of severity of motor symptoms. Reduced initiation of thought and behaviour and emotional blunting characterised PD patients, without confounding effects of motor disability.}, } @article {pmid28388580, year = {2017}, author = {Lian, K and Ma, C and Hao, C and Li, Y and Zhang, N and Chen, YH and Liu, S}, title = {TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.}, journal = {Oncotarget}, volume = {8}, number = {30}, pages = {48889-48904}, pmid = {28388580}, issn = {1949-2553}, mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics/metabolism ; Disease Models, Animal ; Female ; Gene Expression ; Heterografts ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mice ; Middle Aged ; NF-kappa B/*metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Proto-Oncogene Proteins c-akt/*metabolism ; *Signal Transduction ; Tumor Burden ; }, abstract = {TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. Its role in breast cancer has not been evaluated. We report here that TIPE3 protein was significantly upregulated in human breast cancer tissues as compared with adjacent non-tumor tissues from the same patients. The level of TIPE3 protein in invasive ductal carcinoma was significant higher than that in ductal carcinoma in situ (DCIS), and the level of TIPE3 in lymphatic metastasized carcinoma was higher than that in invasive ductal carcinoma from the same patients. Additionally, the level of TIPE3 protein was positively correlated with the level of human epidermal growth factor receptor 2 (HER-2), and TIPE3 expression was significantly higher in high-invasive breast cancer cell lines than that in low-invasive cell lines. Importantly, TIPE3 knockdown in breast cancer cells inhibited cell proliferation, migration, and invasion in vitro, whereas TIPE3 overexpression had the opposite effect. In mice, TIPE3 expression significantly promoted the metastasis of breast cancer cells. TIPE3 expression also increased the level of MMP2 and uPA, and the activation of the AKT and NF-κB signaling pathways. These results demonstrate that TIPE3 may promote breast cancer growth and metastasis through AKT and NF-κB, and may serve as a potential biomarker for breast cancer metastasis.}, } @article {pmid28387663, year = {2017}, author = {Ji, CL and Li, XL and He, YP and Li, DD and Gu, XG and Xu, HX}, title = {Quantitative parameters of contrast-enhanced ultrasound in breast invasive ductal carcinoma: The correlation with pathological prognostic factors.}, journal = {Clinical hemorheology and microcirculation}, volume = {66}, number = {4}, pages = {333-345}, doi = {10.3233/CH-170251}, pmid = {28387663}, issn = {1875-8622}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Contrast Media/*therapeutic use ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy/*methods ; Prognosis ; Retrospective Studies ; Ultrasonography/*methods ; }, abstract = {PURPOSE: To investigate the correlation between quantitative parameters on contrast-enhanced ultrasound (CEUS) and pathological prognostic factors in patients with breast invasive ductal carcinomas (IDCs).

MATERIALS AND METHODS: 102 patients with pathologically proven IDCs were retrospectively enrolled and all were preoperatively evaluated by CEUS. Quantitative analysis was conducted using the SonoLiver® software. On the parametric imaging, the data of rise time (RT), time to peak (TTP), mean transit time (mTT) and maximum intensity (IMAX) were recorded. Pathological prognostic factors, including histological grade, tumor diameter, lymph node status, estrogen receptor (ER), progesterone receptor (PR), C-erb-B2 and Ki-67 expression were evaluated. Correlation of enhancement parameters with pathological prognostic factors was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance and operator consistency was evaluated.

RESULTS: The RTs and TTPs for lower grade IDCs (grade I or II) and higher histological grade IDCs (grade III) were 9.3 s±3.9 vs. 11.4 s±5.4 (p = 0.016), 11.6 s±6.1 vs. 14.7 s±7.7 (p = 0.028), respectively. The RTs for positive-C-erbB-2 expression and negative-C-erbB-2 expression IDCs were 10.1 s±4.5 vs. 11.9 s±6.0 (p = 0.047). The IMAX showed statistical difference between IDCs with negative-ER and those with positive-ER (p = 0.003), as well as IDCs with negative-PR and those with positive-PR (p = 0.019). The ROC analysis showed that, for the differentiation ER expression, the cut-off point for IMAX was 648.8% with an Az value of 0.718 (95% CI: 0.599-0.836), and the sensitivity and specificity were 63.6% and 70.2% respectively. The intra-operator consistency of the RT, TTP, mTT and IMAX were excellent with an overall ICC of 0.893, 0.858, 0.984 and 0.800, respectively (all p < 0.001).

CONCLUSIONS: Quantitative analysis of CEUS may be a useful and objective method in predicting pathological prognostic factors in breast IDCs.}, } @article {pmid28387363, year = {2017}, author = {Liang, SJ and Liu, B and Hu, W and Zhou, K and Ang, LK}, title = {Thermionic Energy Conversion Based on Graphene van der Waals Heterostructures.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {46211}, pmid = {28387363}, issn = {2045-2322}, abstract = {Seeking for thermoelectric (TE) materials with high figure of merit (or ZT), which can directly converts low-grade wasted heat (400 to 500 K) into electricity, has been a big challenge. Inspired by the concept of multilayer thermionic devices, we propose and design a solid-state thermionic devices (as a power generator or a refrigerator) in using van der Waals (vdW) heterostructure sandwiched between two graphene electrodes, to achieve high energy conversion efficiency in the temperature range of 400 to 500 K. The vdW heterostructure is composed of suitable multiple layers of transition metal dichalcogenides (TMDs), such as MoS2, MoSe2, WS2 and WSe2. From our calculations, WSe2 and MoSe2 are identified as two ideal TMDs (using the reported experimental material's properties), which can harvest waste heat at 400 K with efficiencies about 7% to 8%. To our best knowledge, this design is the first in combining the advantages of graphene electrodes and TMDs to function as a thermionic-based device.}, } @article {pmid28385191, year = {2017}, author = {Hidmark, AS and Nawroth, PP and Fleming, T}, title = {STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.}, journal = {Journal of neuroimmunology}, volume = {306}, number = {}, pages = {76-82}, doi = {10.1016/j.jneuroim.2017.03.008}, pmid = {28385191}, issn = {1872-8421}, mesh = {Animals ; Antibiotics, Antineoplastic/toxicity ; Antigens, CD/metabolism ; Cytokines/metabolism ; Diabetes Mellitus, Experimental/chemically induced/*pathology/*physiopathology ; Disease Models, Animal ; Flow Cytometry ; Ganglia, Spinal/drug effects/*pathology ; Hyperalgesia/etiology ; Intercellular Adhesion Molecule-1/metabolism ; Leukocytes/pathology ; Macrophages/drug effects/pathology ; Mice ; Mice, Inbred C57BL ; Sciatic Nerve/drug effects/*pathology ; Streptozocin/toxicity ; Time Factors ; }, abstract = {Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45[+] immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.}, } @article {pmid28384967, year = {2017}, author = {Hammoda, GE and El-Hefnawy, SM and Abdou, AG and Abdallah, RA}, title = {Human Epidermal Growth Factor Receptor-3 mRNA Expression as a Prognostic Marker for Invasive Duct Carcinoma not Otherwise Specified.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {11}, number = {2}, pages = {XC01-XC05}, pmid = {28384967}, issn = {2249-782X}, abstract = {INTRODUCTION: Breast cancer is the most common cancer in women and the Erythroblastosis Oncogene B(ErbB) receptor family holds crucial role in its pathogenesis. Human Epidermal Growth Factor Receptor 3 (HER-3) gene over expression in breast tissue has been associated with aggressive clinical behaviour and bad prognosis.

AIM: To evaluate HER-3 mRNA expression level as a prognostic marker for breast cancer and to correlate its level with other established prognostic parameters.

MATERIALS AND METHODS: This study was carried out on specimens of 100 cases that were divided into 40 patients presented with fibroadenoma and 60 patients presented with Invasive Ductal Carcinoma (IDC) not otherwise specified and underwent modified radical mastectomy. All specimens were investigated for HER-2/neu, ER and PR expression by Immunohistochemistry (IHC) and quantitative assay of HER-3 mRNA expression using real time PCR technique.

RESULTS: There was a significant high HER3 mRNA level in carcinoma cases compared to fibroadenoma. In malignant cases, HER3 mRNA level was significantly associated with advanced T stage, advanced N stage, number of positive lymph nodes, large tumour size and cases associated with an adjacent in situ component. Moreover, HER-3 mRNA level was of highest values in Her-2/neu positive group followed by triple negative cases with the lowest level in luminal group (p<0.05).

CONCLUSION: HER-3 gene is upregulated in IDC especially those carrying poor prognostic features. HER-3 mRNA level may identify a subset of patients with a poor prognosis, and who could undergo further evaluation for the efficacy of HER3 targeted anticancer therapy.}, } @article {pmid28382636, year = {2017}, author = {Marmor, S and Hui, JYC and Huang, JL and Kizy, S and Beckwith, H and Blaes, AH and Rueth, NM and Tuttle, TM}, title = {Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.}, journal = {Cancer}, volume = {123}, number = {16}, pages = {3015-3021}, doi = {10.1002/cncr.30699}, pmid = {28382636}, issn = {1097-0142}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Carcinoma, Lobular/*drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Kaplan-Meier Estimate ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Registries ; Retrospective Studies ; Social Class ; Survival Rate ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC.

METHODS: Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling.

RESULTS: In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P < .01) among those who received endocrine therapy plus chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P < .01) among those who received endocrine therapy plus chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46).

CONCLUSIONS: Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society.}, } @article {pmid28382159, year = {2017}, author = {Lee, HT and Liu, SP and Lin, CH and Lee, SW and Hsu, CY and Sytwu, HK and Hsieh, CH and Shyu, WC}, title = {A Crucial Role of CXCL14 for Promoting Regulatory T Cells Activation in Stroke.}, journal = {Theranostics}, volume = {7}, number = {4}, pages = {855-875}, pmid = {28382159}, issn = {1838-7640}, mesh = {Animals ; Chemokines, CXC/*metabolism ; Dendritic Cells/immunology ; Humans ; *Lymphocyte Activation ; Rats, Sprague-Dawley ; Stroke/*physiopathology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Inflammatory processes have a detrimental role in the pathophysiology of ischemic stroke. However, little is known about the endogenous anti-inflammatory mechanisms in ischemic brain. Here, we identify CXCL14 as a critical mediator of these mechanisms. CXCL14 levels were upregulated in the ischemic brains of humans and rodents. Moreover, hypoxia inducible factor-1α (HIF-1α) drives hypoxia- or cerebral ischemia (CI)-dependent CXCL14 expression via directly binding to the CXCL14 promoter. Depletion of CXCL14 inhibited the accumulation of immature dendritic cells (iDC) or regulatory T cells (Treg) and increased the infarct volume, whereas the supplementation of CXCL14 had the opposite effects. CXCL14 promoted the adhesion, migration, and homing of circulating CD11c[+] iDC to the ischemic tissue via the upregulation of the cellular prion protein (PrP[C]), PECAM-1, and MMPs. The accumulation of Treg in ischemic areas of the brain was mediated through a cooperative effect of CXCL14 and iDC-secreted IL-2-induced Treg differentiation. Interestingly, CXCL14 largely promoted IL-2-induced Treg differentiation. These findings indicate that CXCL14 is a critical immunomodulator involved in the stroke-induced inflammatory reaction. Passive CXCL14 supplementation provides a tractable path for clinical translation in the improvement of stroke-induced neuroinflammation.}, } @article {pmid28375214, year = {2017}, author = {Gallet, R and Violle, C and Fromin, N and Jabbour-Zahab, R and Enquist, BJ and Lenormand, T}, title = {The evolution of bacterial cell size: the internal diffusion-constraint hypothesis.}, journal = {The ISME journal}, volume = {11}, number = {7}, pages = {1559-1568}, pmid = {28375214}, issn = {1751-7370}, mesh = {Bacteria/*cytology/*genetics ; *Biological Evolution ; *Cell Size ; }, abstract = {Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.}, } @article {pmid28373460, year = {2017}, author = {Inoue, Y and Yamashita, N and Tokunaga, E and Tanaka, K and Ueo, H and Saeki, H and Oki, E and Yamamoto, H and Maehara, Y}, title = {A Locally Advanced Breast Cancer that Achieved pCR with Pertuzumab, Trastuzumab and Docetaxel: Case Report.}, journal = {Anticancer research}, volume = {37}, number = {4}, pages = {1917-1921}, doi = {10.21873/anticanres.11530}, pmid = {28373460}, issn = {1791-7530}, mesh = {Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Docetaxel ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Remission Induction ; Taxoids/administration & dosage ; Trastuzumab/administration & dosage ; }, abstract = {We herein report a case of locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that achieved a pathological complete response (pCR) with pertuzumab, trastuzumab and docetaxel therapy. A 70-year-old female presented with an elastic hard mass, 5.0 cm in diameter with broad redness and edema of the skin in her right breast. Swollen lymph nodes were also recognized in the right axilla. The pathological diagnosis was invasive ductal carcinoma and its biological character was estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, HER2 3+ and Ki-67 index 60%. The patient was finally diagnosed with primary unresectable, locally advanced breast cancer and started on pertuzumab, trastuzumab and docetaxel combination therapy. The tumor subsequently reduced in size and, after 4 cycles of this therapy, she underwent surgery. The histopathological examination of the postoperative specimen showed pCR in both the primary tumor and axillary lymph nodes.}, } @article {pmid28370063, year = {2017}, author = {Liu, H and Zheng, Y and Liang, D and Tang, P and Ren, F and Zhang, L and Zhao, Z}, title = {Total variation based DCE-MRI decomposition by separating lesion from background for time-intensity curve estimation.}, journal = {Medical physics}, volume = {44}, number = {6}, pages = {2321-2331}, doi = {10.1002/mp.12242}, pmid = {28370063}, issn = {2473-4209}, mesh = {Algorithms ; Breast ; Breast Neoplasms/*diagnostic imaging ; Contrast Media ; Humans ; Image Enhancement ; *Image Interpretation, Computer-Assisted ; *Magnetic Resonance Imaging ; Phyllodes Tumor/*diagnostic imaging ; }, abstract = {PURPOSE: This study aims to obtain the accurate time intensity curve (TIC) of a dynamic contrast-enhanced magnetic resonance image (DCE-MRI) by eliminating the normal tissue enhancement and obtaining pure lesion information. The TIC of DCE-MRI is sometimes distorted because of the influence of normal tissue. In this paper, a new tracer-kinetic modeling based on total variation (DC-TV) is proposed to address this problem by decomposing the DCE-MRI into the normal tissue image and the lesion image. As TIC generation is not standardized and a credible program is expected, an accurate TIC generation is presented in this paper.

MATERIALS AND METHODS: We propose a new tracer-kinetic model DC-TV to decompose the lesion region in breast DCE-MRIs. The original image is decomposed into a normal tissue image and a lesion image to obtain the pure lesion enhancement information. The acquired lesion images are smooth and correspond to the diffusion of the contrast agent in the lesion. The normal tissue image sequences are stable and correspond to the enhanced normal tissue. To speed up the computational process of our convergent algorithm, the split Bregman iteration algorithm is applied. To compare the algorithm results, images generated by decomposed methods without normal tissue constraint based on total variation are compared with those generated by our method. The performance of the proposed method is evaluated by the correlation of normal tissue images with the lesion classification accuracy of lesion images.

RESULTS: Ninety-eight lesions, including 40 benign and 58 malignant, are evaluated. The dataset includes various typical pathologies of the breast such as invasive ductal carcinoma, ductal carcinoma in situ, tubular carcinoma, phyllodes tumor, hyperplasia, and fibroadenoma, among others. The area under the ROC for the pure lesion enhancement images acquired by DC-TV is greater than that acquired by the original DCE-MRIs.

CONCLUSIONS: The pure enhancement information from the original breast DCE-MRI lesions can be successfully obtained using our DC-TV. The TICs based on the acquired pure enhancement information closely conform to three-time-point model, which is a classic diagnosis rule. The experiment shows that DC-TV provide a credible TIC generation program.}, } @article {pmid28368663, year = {2017}, author = {Chamming's, F and Kao, E and Aldis, A and Ferré, R and Omeroglu, A and Reinhold, C and Mesurolle, B}, title = {Imaging features and conspicuity of invasive lobular carcinomas on digital breast tomosynthesis.}, journal = {The British journal of radiology}, volume = {90}, number = {1073}, pages = {20170128}, pmid = {28368663}, issn = {1748-880X}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Carcinoma, Lobular/*diagnostic imaging/*pathology ; Female ; Humans ; *Mammography ; Neoplasm Invasiveness ; Retrospective Studies ; }, abstract = {OBJECTIVE: To review the imaging features of invasive lobular carcinoma (ILC) seen on digital breast tomosynthesis (DBT) in comparison with invasive ductal carcinoma (IDC), and to evaluate whether DBT could improve conspicuity and tumour size assessment of ILC in comparison with digital mammography (DM).

METHODS: Institutional review board with waiver of informed consent was obtained for this retrospective study. Patients with ILC or IDC who underwent DBT and DM at the time of diagnosis were included. DM and DBT images were reviewed in consensus by two breast radiologists in order to assess imaging features, conspicuity and maximum tumour diameter of ILC and IDC. Pathology on the surgical specimen was considered the standard of reference for assessment of tumour size.

RESULTS: 43 patients (20 patients with ILC and 23 patients with IDC) were included. On DBT, compared with IDC, ILC presented less frequently as masses (40% vs 78%) (p = 0.01) and more frequently as isolated distortion (20% vs 0%) (p = 0.03). ILC presented more often as asymmetries (60%) than masses (20%) on DM (p = 0.02) but not on DBT (35% vs 40%; p = 1.00). Conspicuity of ILC was significantly higher on DBT than on DM (p = 0.002), while the difference between the two techniques was not significant for IDC (p = 0.2). Regarding ILC, concordance in tumour size measurement between DBT and pathology was fair (intraclass correlation coefficient = 0.24).

CONCLUSION: ILC rarely presented as dense masses but frequently demonstrated architectural distortion on DBT. DBT increased lesion conspicuity but failed to accurately assess tumour size of ILC. Advances in knowledge: (1) This study describes specific features of ILC on DBT. (2) It shows that DBT can improve conspicuity of ILC.}, } @article {pmid28365833, year = {2017}, author = {Truin, W and Roumen, RMH and Siesling, S and van de Vijver, KK and Tjan-Heijnen, VCG and Voogd, AC}, title = {Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors.}, journal = {Breast cancer research and treatment}, volume = {164}, number = {1}, pages = {133-138}, pmid = {28365833}, issn = {1573-7217}, mesh = {Aged ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Carcinoma, Lobular/*diagnosis/genetics/pathology ; Diagnosis, Differential ; Estrogens/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Netherlands ; Progesterone/genetics ; Receptors, Estrogen/*genetics ; Receptors, Progesterone/*genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: Differences in estrogen (ER) and progesterone (PR) expression between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) could be an underlying reason for the difference in chemo-sensitivity and response to hormonal therapy between ILC and IDC. The aim of this study was to investigate the differences in ER and PR expression levels between postmenopausal patients with hormonal receptor-positive ILC and IDC.

METHODS: We included all ER and/or PR receptor-positive ILC and IDC, diagnosed between January 2011 and December 2013 from the population-based Netherlands Cancer Registry. A semi-quantitative classification was used to analyze differences in ER/PR expression, which consisted of three ER expression classes: 10-69, 70-89, and ≥90%. Differences in ER and PR expression levels between IDC and ILC were analyzed according to age group, tumor size, axillary nodal status, grade, and HER2 status.

RESULTS: In total, 26,339 ER and/or PR-positive breast cancers were included in the study, of which 17% were ILC and 83% IDC. In patients with IDC, 86% of the tumors showed an ER expression level of 90% or more, compared to 84% in those with ILC. In both IDC and ILC a PR expression level of 90% or more was observed in 54% of the tumors. In postmenopausal patients aged 50-69 years no significant differences could be observed in ER and PR expression levels between ILC and IDC.

CONCLUSION: Patients with ER and PR-positive ILC and IDC have similar quantitative ER and PR expression profiles, implicating that ER/PR expression is unlikely to be a confounding factor in studies concerning chemo-sensitivity of ILC and IDC.}, } @article {pmid28363948, year = {2017}, author = {Taylor, D and O'Hanlon, S and Latham, B}, title = {False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, pmid = {28363948}, issn = {1757-790X}, mesh = {Biopsy, Large-Core Needle ; Breast/*diagnostic imaging/pathology/surgery ; Breast Density ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Contrast Media ; Diagnostic Errors ; Elective Surgical Procedures ; Female ; Humans ; Mastectomy ; Middle Aged ; Multimodal Imaging ; Sensitivity and Specificity ; Ultrasonography, Mammary/*methods ; }, abstract = {A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position. On ultrasound (US), a corresponding 13×9×10 mm irregular hypoechoic mass with internal vascularity was noted and both breasts had a complex heterogeneous fibroglandular background pattern. US-guided core biopsy with marker clip insertion was performed with the diagnosis of a grade 2 invasive ductal carcinoma (IDC). In view of the parenchymal pattern on mammography and US, contrast-enhanced spectral mammography (CESM) was performed for local staging. Mild background enhancement was noted, but there was no enhancement at the lesion site. The patient elected to have bilateral mastectomies and sentinel node biopsies. Final histopathology showed a node negative 11 mm grade 2 oestrogen and progesterone receptor positive, IDC.}, } @article {pmid28363741, year = {2017}, author = {Dinerman, BF and Bernstein, AN and Khani, F and Hu, JC}, title = {Intraductal Carcinoma of the Prostate: A Risk for Rapid Recurrence.}, journal = {Urology}, volume = {105}, number = {}, pages = {e1-e2}, doi = {10.1016/j.urology.2017.03.030}, pmid = {28363741}, issn = {1527-9995}, mesh = {Carcinoma, Ductal/diagnostic imaging/*pathology/*therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Prostatic Neoplasms/diagnostic imaging/*pathology/*therapy ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P), recently defined by the World Health Organization in 2016, is a distinct histologic entity associated with an aggressive clinical course, including increased risk of biochemical recurrence, metastasis, and mortality. Differential diagnosis includes intraductal spread of urothelial carcinoma, prostatic ductal carcinoma, and high-grade prostatic intraepithelial neoplasia. BRCA mutations are associated with an increased risk of IDC-P. The presence of IDC-P on initial biopsy or radical prostatectomy should trigger aggressive treatment and should be considered a contraindication to active surveillance, regardless of tumor volume.}, } @article {pmid28357109, year = {2017}, author = {Hashemi, SM and Mahmoudi Shan, S and Jahantigh, M and Allahyari, A}, title = {Atypical breast adenosquamous carcinoma following acute myeloid leukemia in a middle-aged woman: A case report.}, journal = {Molecular and clinical oncology}, volume = {6}, number = {2}, pages = {271-275}, pmid = {28357109}, issn = {2049-9450}, abstract = {Adenosquamous carcinoma of the breast is a rare cancer that develops as glands and tubules admixed with solid nests of squamous cells in a spindle cell background. Furthermore, its occurrence following AML is also rare. To the best of our knowledge, based on a review of the relevant literature, thus far there have not been any welldocumented cases. In the present case report, we report on a middle-aged woman with a 2year history of acute myeloid leukemia (AML) who was admitted to hospital due to a mass in the right breast, with concurrent cutaneous lesions on the breast. The clinical and pathological investigations resulted in the diagnosis of adenosquamous carcinoma of the breast. The patient underwent a modified radical mastectomy (MRM). Subsequently, the patient received chemotherapy, involved-field radiation therapy and target therapy. At 9 months after the final cycle of chemotherapy, and while she was on targeted therapy with trastuzumab (6 mg administered every 3 weeks), the patient presented with extensive dermatomal skin lesions. A biopsy report revealed metastatic lesions of invasive ductal carcinoma in the abdomen, so chemotherapy resumed with a course lasting for 6 cycles, with the identical treatments, but lacking trastuzumab.}, } @article {pmid28357074, year = {2017}, author = {Zhuang, C and Hong, X and Liu, J and Luo, X and Mo, H}, title = {TRAF6 regulates the effects of polarized maturation of tolerability: Marrow-derived dendritic cells on collagen-induced arthritis in mice.}, journal = {Biomedical reports}, volume = {6}, number = {2}, pages = {206-210}, pmid = {28357074}, issn = {2049-9434}, abstract = {The study aimed to investigate the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and a differentially mature dendritic cell (mDC) in collagen-induced arthritis (CIA) mice and to determine whether or not TRAF6 regulates the activation of an immature dendritic cell (iDC) and inhibits iDC maturation to induce immune tolerance. The mouse bone marrow stem cells were induced with recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) to differentiate immature dendritic cells (DCs), which were divided into four groups with different maturation states: rmGM-CSF, rmIL-4; TNF-α; LPS; and FK506 group. The levels of the cell surfaces of CD80, CD86, and MHI-II were analyzed by flow cytometry to prove DCs at different levels of maturity. The expression of IL-12 in DCs at different maturation states was detected by enzyme-linked immunosorbent assay (ELISA). The expression of TRAF6 mRNA and protein in each group of DCs was detected by a reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. The results revealed that the differentiation of bone marrow cells into iDCs was significantly induced by cytokines (rmGM-CSF, IL-4). CD80, CD86, MHC-II were expressed in the four groups, and the difference between them was statistically significant (P<0.05). A higher degree of DC differentiation led to a gradual increase of IL-12 secretion in the four groups. The difference was statistically significant (P<0.05) for this secretion (group D, 10,620.73±276.73 pg/ml). The expression levels of TRAF6 mRNA were significantly higher in group D than those in the other three groups (P<0.01). Although there was no significant difference in the expression levels of TRAF6 mRNA between groups B and C, the expression levels of TRAF6 mRNA between groups B and C were higher than those of the control group. The TRAF6 protein expression was higher in group D than that in the other three groups (P<0.01), and the difference was statistically significant. There was a statistically significant difference in the TRAF6 protein expression between group A and groups B and C, but the expression in group C was higher than that in group B (P<0.01). In conclusion, the expression of co-stimulatory molecules gradually increased in the DCs of different maturation states, and the expression of IL-12, TRAF6 mRNA, and TRAF6 protein positively correlated with the degree of DC maturation. TRAF6 is important in iDC polarity and maturation.}, } @article {pmid28355358, year = {2017}, author = {Carrara, GF and Scapulatempo-Neto, C and Abrahão-Machado, LF and Brentani, MM and Nunes, JS and Folgueira, MA and Vieira, RA}, title = {Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {72}, number = {3}, pages = {134-142}, pmid = {28355358}, issn = {1980-5322}, mesh = {Adult ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma/*drug therapy/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/*etiology ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Analysis ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {OBJECTIVE:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer.

METHODS:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival.

RESULTS:: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01).

CONCLUSIONS:: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.}, } @article {pmid28353289, year = {2017}, author = {Masferrer, L and Garre-Olmo, J and Caparrós, B}, title = {Factor structure and concurrent construct validity of ICG among bereaved substance users.}, journal = {Actas espanolas de psiquiatria}, volume = {45}, number = {2}, pages = {47-55}, pmid = {28353289}, issn = {1578-2735}, mesh = {Cross-Sectional Studies ; Female ; *Grief ; Humans ; Male ; Middle Aged ; Patient Health Questionnaire ; Psychometrics ; Reproducibility of Results ; Substance-Related Disorders/*etiology/*psychology ; }, abstract = {BACKGROUND: It is important to understand the repercussions of Complicated Grief (CG) symptoms in addictions. There are no studies to date which have examined the psychometric properties of any test of bereavement among people with substance use disorder (SUD). Participants with SUD can have a different experience of bereavement from other people and therefore could respond differently to the usual instruments which assess CG symptomatology.

METHOD: This study aims to establish the psychometric properties of the Spanish adaption of the Inventory of Complicated Grief (ICG) in a sample of 196 bereaved drug dependent patients.

RESULTS: Results indicate that the internal consistency of the Spanish ICG was high (Cronbach’s alpha=0.922). The Spanish IDC shows good psychometric properties and it is a useful tool to discriminate adaptive reactions to symptomatology of complicated grief. Four factors were identified: discomfort, non-acceptance, loneliness-isolation and presence of deceased. Those factors showed a good internal reliability (minimum Cronbach’s alpha=0.78).

CONCLUSIONS: The results of the current study confirm the multidimensionality of CG’s symptomatology construct.}, } @article {pmid28349009, year = {2016}, author = {Jha, KK and Gupta, SK}, title = {An atypical presentation of infiltrating ductal carcinoma.}, journal = {Journal of family medicine and primary care}, volume = {5}, number = {4}, pages = {868-870}, pmid = {28349009}, issn = {2249-4863}, abstract = {A 64-year-old African-American female presented with nonbloody nipple discharge. Clinical and cytological examination of the discharge was normal. The mammography suggested pleomorphic calcification in the left breast. A stereotactic biopsy showed ductal carcinoma in situ and her estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2-neu receptor were negative. We removed the tumor tissue through lumpectomy and found that the mass was invasive ductal carcinoma. This case report highlights invasive ductal carcinoma, presenting with unilateral nipple discharge.}, } @article {pmid28345134, year = {2018}, author = {Abdeen, Z and Brunstein-Klomek, A and Nakash, O and Shibli, N and Nagar, M and Agha, H and Hallaq, S and Kanat-Maymon, Y and Juerges, H and Levav, I and Qasrawi, R}, title = {The Association Between Political Violence and the Connection Between Bullying and Suicidality Among Palestinian Youth.}, journal = {Suicide & life-threatening behavior}, volume = {48}, number = {1}, pages = {95-104}, doi = {10.1111/sltb.12338}, pmid = {28345134}, issn = {1943-278X}, mesh = {Adolescent ; *Arabs/psychology/statistics & numerical data ; Bullying/*prevention & control ; Crime Victims/*psychology ; Demography ; Female ; Humans ; Israel/epidemiology ; Male ; Mental Health ; Politics ; Schools/statistics & numerical data ; Socioeconomic Factors ; Statistics as Topic ; *Suicide, Attempted/ethnology/prevention & control/psychology ; Surveys and Questionnaires ; *Violence/prevention & control/psychology ; }, abstract = {We examined the association between protracted political violence and the connection between bullying and suicidality among Palestinian adolescents. Data were collected from a representative sample of Palestinian students (N = 5,713) from 100 schools in the West Bank and East Jerusalem who completed an in-class survey. Students who were victims of bullying or bully victims who were exposed to political violence were at higher risk for suicide attempts compared to students who were victims of bullying or bully victims but not exposed to political violence. Political violence moderated the association between bullying and suicide attempts after controlling for socio demographic and other mental health variables.}, } @article {pmid28342640, year = {2017}, author = {Porter, LH and Lawrence, MG and Ilic, D and Clouston, D and Bolton, DM and Frydenberg, M and Murphy, DG and Pezaro, C and Risbridger, GP and Taylor, RA}, title = {Systematic Review Links the Prevalence of Intraductal Carcinoma of the Prostate to Prostate Cancer Risk Categories.}, journal = {European urology}, volume = {72}, number = {4}, pages = {492-495}, doi = {10.1016/j.eururo.2017.03.013}, pmid = {28342640}, issn = {1873-7560}, mesh = {Carcinoma/*epidemiology/pathology/therapy ; Cell Proliferation ; Humans ; Male ; Neoplasm Grading ; Prevalence ; Prostatic Neoplasms/*epidemiology/pathology/therapy ; Risk Assessment ; Risk Factors ; }, abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is associated with poor prognosis. While it is often regarded as a rare pathology, the prevalence of IDC-P remains unclear, with variable reports from small and disparate patient populations. To determine how common IDC-P is across the spectrum of prostate cancer, we conducted a systematic review correlating IDC-P prevalence with prostate cancer risk. Electronic searches of the OVID Medline, PubMed, and Scopus literature databases identified 38 patient cohorts in 24 articles, which were divided between four prostate cancer risk categories (low, moderate, high, and recurrent or metastatic disease). This review, which included radical prostatectomy and prostate biopsy specimens from >7000 patients, revealed an unexpectedly high rate of IDC-P. The IDC-P prevalence increased from 2.1% in low-risk patient cohorts to 23.1%, 36.7%, and 56.0% in moderate-risk, high-risk, and metastatic or recurrent disease risk categories, respectively (p<0.0001). IDC-P was also highly prevalent in tumours following androgen deprivation therapy or chemotherapy (60%). Contrary to common perceptions, this study demonstrates a strong association between IDC-P prevalence and aggressive prostate cancer, with a significantly higher frequency in high-risk disease. Greater recognition and systematic reporting of IDC-P may improve patient risk stratification.

PATIENT SUMMARY: Prostate cancer can grow within ducts of the prostate, as well as in prostate tissue. By reviewing all reports describing prostate cancer growing within ducts, we found that it occurs more commonly than many scientists and clinicians appreciate, especially in aggressive prostate cancers. We conclude that there should be more awareness of this pattern of prostate cancer.}, } @article {pmid28333404, year = {2017}, author = {Chang Sen, LQ and Berg, WA and Carter, GJ}, title = {Upgrade Rate and Imaging Features of Atypical Apocrine Lesions.}, journal = {The breast journal}, volume = {23}, number = {5}, pages = {569-578}, doi = {10.1111/tbj.12789}, pmid = {28333404}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apocrine Glands/*pathology ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Female ; Fibrocystic Breast Disease/diagnostic imaging/pathology ; Humans ; Mammography ; Middle Aged ; }, abstract = {The purpose of our work was to identify imaging features of atypical apocrine lesions and determine the rate of upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma at excision after such a diagnosis on percutaneous breast biopsy. From January 1, 2006, through October 8, 2013, a total of 33,157 breast core biopsies were performed at University of Pittsburgh Medical Center. Of those, 58 (0.2%) showed atypical apocrine lesions. For 24, atypical apocrine adenosis (AAA) or atypical apocrine metaplasia (AAM) was the only risk lesion, with no known ipsilateral malignancy, and the results of excision were available. The median patient age was 58 years (range 43-88). Among 24 atypical apocrine lesions (20 AAA and 4 AAM), four (16.7%; 95% confidence interval: 4.7, 37.4) were upgraded at excision: one invasive ductal carcinoma (grade 2, 0.2 cm, estrogen receptor positive, progesterone receptor positive, HER2/Neu negative) and three DCIS (two grade 3, one grade 2). All four upgraded lesions were AAA (20%; 4/20). Twelve AAA were seen as an irregular (n = 9) or circumscribed (n = 3) mass on ultrasound; three masses had calcifications. Six of 20 (30%) AAA were seen on biopsy of calcifications only and calcifications were within two AAA lesions at histopathology. One AAA (1/20, 5%) was asymmetry only, and one (1/20, 5%) a persistently enhancing MR focus. All four malignancies were masses on ultrasound (three irregular, one circumscribed), and three malignancies had calcifications (two coarse heterogeneous, one amorphous). While concordant with an irregular or circumscribed mass on imaging, with or without amorphous or coarse heterogeneous calcifications, AAA merits excision with a 20% upgrade rate to malignancy. Further study of AAM is warranted.}, } @article {pmid28332040, year = {2017}, author = {Siciliano, M and Trojano, L and Trojsi, F and Greco, R and Santoro, M and Basile, G and Piscopo, F and D'Iorio, A and Patrone, M and Femiano, C and Monsurrò, M and Tedeschi, G and Santangelo, G}, title = {Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-Italian version: regression based norms and equivalent scores.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {38}, number = {6}, pages = {1059-1068}, pmid = {28332040}, issn = {1590-3478}, mesh = {Adult ; Aged ; Amyotrophic Lateral Sclerosis/*diagnosis/*psychology ; Female ; Humans ; Male ; Middle Aged ; *Neuropsychological Tests ; Reference Values ; Regression Analysis ; }, abstract = {Cognitive assessment for individuals with Amyotrophic Lateral Sclerosis (ALS) can be difficult because of frequent occurrence of difficulties with speech, writing, and drawing. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a recent multi-domain neuropsychological screening tool specifically devised for this purpose, and it assesses the following domains: executive functions, social cognition, verbal fluency and language (ALS-specific), but also memory and visuospatial abilities (Non-ALS specific). ECAS total score ranges from 0 (worst performance) to 136 (best performance). Moreover, a brief caregiver interview provides an assessment of behaviour changes and psychotic symptoms usually associated with ALS patients. The aim of the present study was to provide normative values for ECAS total score and sub-scores in a sample of Italian healthy subjects. Two hundred and seventy-seven Italian healthy subjects (151 women and 126 men; age range 30-79 years; educational level from primary school to university) underwent ECAS and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ECAS total score and sub-scale scores. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-off scores were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between adjusted ECAS total scores with adjusted MoCA total scores (r rho = 0.669, p < 0.0001). The present study provided normative data for the ECAS in an Italian population useful for both clinical and research purposes.}, } @article {pmid28331761, year = {2017}, author = {Külahcı, Ö and Esen, HH and Asut, E and Güngör, S}, title = {Association of ICAM-1, VCAM-1, CYCLIN D1 and Cathepsin D with Clinicopathological Parameters in Breast Carcinoma; an Immunohistochemical Study.}, journal = {The journal of breast health}, volume = {13}, number = {1}, pages = {5-9}, pmid = {28331761}, issn = {1306-0945}, abstract = {OBJECTIVE: Breast carcinoma is the most common malignant tumor detected in women. The hypothesis that increased levels of adhesion molecules and Cathepsin D affect cancerous cells moving away the primary tumor and contributes to migration of the cancerous cell and may cause remote organ metastases is defended. The aim of the present study was to search the association of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), Cyclin D1, cathepsin D immunohistochemically with clinicopathological parameters in the patients diagnosed with invasive ductal breast carcinoma.

MATERIALS AND METHODS: The pathological slides of 153 patients diagnosed with invasive ductal carcinoma were evaluated retrospectively. Three groups were created. Group 1 consisted of patients with positive lymph node metastasis and extranodal tumor invasion; Group 2 consisted of patients with positive axillary lymph node metastasis and negative extranodal tumor invasion and Group 3 consisted of the patients with negative axillary lymph node metastasis. In all groups, 20 paraffin blocks belonging to the primary tumor in the breast were stained by ICAM-1, VCAM-1, Cyclin D1 and Cathepsin D. Findings were examined by comparing with clinicopathological parameters.

RESULTS: The highest number of metastatic axillary lymph nodes and the highest rate of cathepsin D staining were statistically found in the cases with positive axillary lymph node metastasis and extranodal tumor invasion. CerbB2 was negative in the cases with negative ICAM-1 whereas estrogen receptor and progesterone receptor were positive in the cases with positive VCAM-1.

CONCLUSION: The present study reveals significant results for the patients diagnosed with invasive ductal carcinoma through breast biopsy especially before mastectomy in terms of increased number of metastatic axillary lymph nodes and extranodal tumor invasion by immunohistochemical Cathepsin D stain without any additional invasive intervention. Results of the present study may contribute to monitoring and treatment of the patients in the future.}, } @article {pmid28327449, year = {2017}, author = {Wan, S and Lee, HC and Huang, X and Xu, T and Xu, T and Zeng, X and Zhang, Z and Sheikine, Y and Connolly, JL and Fujimoto, JG and Zhou, C}, title = {Integrated local binary pattern texture features for classification of breast tissue imaged by optical coherence microscopy.}, journal = {Medical image analysis}, volume = {38}, number = {}, pages = {104-116}, pmid = {28327449}, issn = {1361-8423}, support = {R00 EB010071/EB/NIBIB NIH HHS/United States ; R21 EY026380/EY/NEI NIH HHS/United States ; R01 CA075289/CA/NCI NIH HHS/United States ; R01 GM098430/GM/NIGMS NIH HHS/United States ; R01 CA178636/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Breast/*diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Microscopy, Confocal/*methods ; Pattern Recognition, Automated/*methods ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, Optical Coherence/*methods ; }, abstract = {This paper proposes a texture analysis technique that can effectively classify different types of human breast tissue imaged by Optical Coherence Microscopy (OCM). OCM is an emerging imaging modality for rapid tissue screening and has the potential to provide high resolution microscopic images that approach those of histology. OCM images, acquired without tissue staining, however, pose unique challenges to image analysis and pattern classification. We examined multiple types of texture features and found Local Binary Pattern (LBP) features to perform better in classifying tissues imaged by OCM. In order to improve classification accuracy, we propose novel variants of LBP features, namely average LBP (ALBP) and block based LBP (BLBP). Compared with the classic LBP feature, ALBP and BLBP features provide an enhanced encoding of the texture structure in a local neighborhood by looking at intensity differences among neighboring pixels and among certain blocks of pixels in the neighborhood. Fourty-six freshly excised human breast tissue samples, including 27 benign (e.g. fibroadenoma, fibrocystic disease and usual ductal hyperplasia) and 19 breast carcinoma (e.g. invasive ductal carcinoma, ductal carcinoma in situ and lobular carcinoma in situ) were imaged with large field OCM with an imaging area of 10 × 10 mm[2] (10, 000 × 10, 000 pixels) for each sample. Corresponding H&E histology was obtained for each sample and used to provide ground truth diagnosis. 4310 small OCM image blocks (500 × 500 pixels) each paired with corresponding H&E histology was extracted from large-field OCM images and labeled with one of the five different classes: adipose tissue (n = 347), fibrous stroma (n = 2,065), breast lobules (n = 199), carcinomas (pooled from all sub-types, n = 1,127), and background (regions outside of the specimens, n = 572). Our experiments show that by integrating a selected set of LBP and the two new variant (ALBP and BLBP) features at multiple scales, the classification accuracy increased from 81.7% (using LBP features alone) to 93.8% using a neural network classifier. The integrated feature was also used to classify large-field OCM images for tumor detection. A receiver operating characteristic (ROC) curve was obtained with an area under the curve value of 0.959. A sensitivity level of 100% and specificity level of 85.2% was achieved to differentiate benign from malignant samples. Several other experiments also demonstrate the complementary nature of LBP and the two variants (ALBP and BLBP features) and the significance of integrating these texture features for classification. Using features from multiple scales and performing feature selection are also effective mechanisms to improve accuracy while maintaining computational efficiency.}, } @article {pmid28326638, year = {2017}, author = {Mizukawa, K and Kobayashi, T and Yamada, N and Hirota, T}, title = {Intervertebral disc calcification with ossification of the posterior longitudinal ligament.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {59}, number = {5}, pages = {622-624}, doi = {10.1111/ped.13243}, pmid = {28326638}, issn = {1442-200X}, mesh = {Calcinosis/complications/*diagnostic imaging ; Cervical Vertebrae/*diagnostic imaging ; Child ; Female ; Humans ; Ossification of Posterior Longitudinal Ligament/complications/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {A 6-year-old girl presented to hospital with a 4 day history of increasing neck pain. White blood cell count was normal with slightly raised C-reactive protein. The patient had a limited range of neck movement, and experienced enhanced pain with neck extension. X-ray and cervical computed tomography (CT) confirmed the diagnosis of cervical intervertebral disc calcification (IDC) and IDC with ossification of the posterior longitudinal ligament (OPLL), respectively. The symptoms improved after approximately 1 week following rest and oral acetaminophen. X-ray 6 months after onset confirmed the disappearance of the calcification. IDC is often reported in children, but IDC with OPLL is extremely rare and has not been previously reported in Japan. We believe that IDC with or without OPLL in children has a good prognosis when treated conservatively.}, } @article {pmid28325697, year = {2017}, author = {Sulaj, A and Kopf, S and Gröne, E and Gröne, HJ and Hoffmann, S and Schleicher, E and Häring, HU and Schwenger, V and Herzig, S and Fleming, T and Nawroth, PP and von Bauer, R}, title = {ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy.}, journal = {Journal of diabetes and its complications}, volume = {31}, number = {6}, pages = {1058-1065}, doi = {10.1016/j.jdiacomp.2017.01.002}, pmid = {28325697}, issn = {1873-460X}, mesh = {Adult ; Aged ; Antigens, CD/analysis/*blood/physiology ; Biomarkers/*blood ; Case-Control Studies ; Cell Adhesion Molecules, Neuronal/analysis/*blood/physiology ; Diabetes Mellitus, Type 2/*blood/*complications/diagnosis ; Diabetic Nephropathies/blood/*diagnosis/etiology ; Disease Progression ; Female ; Fetal Proteins/analysis/*blood/physiology ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND & AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN.

METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy.

RESULTS: Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85±14.99ng/ml vs. 126.88±66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88±66.45ng/ml vs. 197.50±37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes.

CONCLUSIONS: This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.}, } @article {pmid28322912, year = {2017}, author = {Braithwaite, EC and Pickles, A and Sharp, H and Glover, V and O'Donnell, KJ and Tibu, F and Hill, J}, title = {Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner.}, journal = {Physiology & behavior}, volume = {175}, number = {}, pages = {31-36}, pmid = {28322912}, issn = {1873-507X}, support = {G0400577/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Cohort Studies ; Emotions/*physiology ; Female ; Fetal Development/physiology ; Gestational Age ; Humans ; Hydrocortisone/*metabolism ; Infant ; Logistic Models ; Male ; Middle Aged ; Pregnancy ; Prenatal Exposure Delayed Effects/metabolism/*physiopathology ; Self Report ; *Sex Characteristics ; Stress, Psychological/*metabolism/*physiopathology ; Young Adult ; }, abstract = {OBJECTIVE: Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk.

METHOD: The Wirral Child Health and Development Study (WCHADS) cohort (n=1233) included a stratified random sub-sample (n=216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse probability weights.

RESULTS: Maternal prenatal cortisol sampled on waking predicted infant negative emotionality in a sex-dependent manner (interaction term, p=0.005); female infants exposed to high levels of prenatal cortisol were more negative (Beta=0.440, p=0.042), whereas male infants were less negative (Beta=-0.407, p=0.045). There was no effect of the 30-min post-waking measure or evening cortisol.

DISCUSSION: Our findings add to an emerging body of work that has highlighted sex differences in fetal programming, whereby females become more reactive following prenatal stress, and males less reactive. A more complete understanding of sex-specific developmental trajectories in the context of prenatal stress is essential for the development of targeted prevention strategies.}, } @article {pmid28318462, year = {2017}, author = {Scouten, WT and Mehalick, ML and Yoder, E and McCoy, A and Brannock, T and Riddle, MS}, title = {The Epidemiology of Operation Stress during Continuing Promise 2011: A Humanitarian Response and Disaster Relief Mission aboard a US Navy Hospital Ship.}, journal = {Prehospital and disaster medicine}, volume = {32}, number = {4}, pages = {393-402}, doi = {10.1017/S1049023X17000218}, pmid = {28318462}, issn = {1945-1938}, mesh = {Adult ; Female ; Hospitals, Military ; Humans ; Incidence ; Male ; *Medical Missions ; Military Medicine ; Military Personnel/*psychology ; Occupational Diseases/epidemiology/*psychology ; Retrospective Studies ; Ships ; Stress, Psychological/epidemiology/*psychology ; Surveys and Questionnaires ; United States/epidemiology ; }, abstract = {UNLABELLED: Introduction Operational stress describes individual behavior in response to the occupational demands and tempo of a mission. The stress response of military personnel involved in combat and peace-keeping missions has been well-described. The spectrum of effect on medical professionals and support staff providing humanitarian assistance, however, is less well delineated. Research to date concentrates mainly on shore-based humanitarian missions. Problem The goal of the current study was to document the pattern of operational stress, describe factors responsible for it, and the extent to which these factors impact job performance in military and civilian participants of Continuing Promise 2011 (CP11), a ship-based humanitarian medical mission.

METHODS: This was a retrospective study of Disease Non-Battle Injury (DNBI) data from the medical sick-call clinic and from weekly self-report questionnaires for approximately 900 US military and civilian mission participants aboard the USNS COMFORT (T-AH 20). The incidence rates and job performance impact of reported Operational Stress/Mental Health (OS/MH) issues and predictors (age, rank, occupation, service branch) of OS/MH issues (depression, anxiety) were analyzed over a 22-week deployment period.

RESULTS: Incidence rates of OS/MH complaints from the sick-call clinic were 3.7% (4.5/1,000 persons) and 12.0% (53/1,000 persons) from the self-report questionnaire. The rate of operational stress increased as the mission progressed and fluctuated during the mission according to ship movement. Approximately 57% of the responders reported no impact on job performance. Younger individuals (enlisted ranks E4-6, officer ranks O1-3), especially Air Force service members, those who had spent only one day off ship, and those who were members of specific directorates, reported the highest rates of operational stress.

CONCLUSION: The overall incidence of OS/MH complaints was low in participants of CP11 but was under-estimated by clinic-based reporting. The OS/MH complaints increased as the mission progressed, were more prevalent in certain groups, and appeared to be related to ship's movement. These findings document the pattern of operational stress in a ship-based medical humanitarian mission and confirm unique ship-based stressors. This information may be used by planners of similar missions to develop mitigation strategies for known stressors and by preventive medicine, behavioral health specialists, and mission leaders to develop sensitive surveillance tools to better detect and manage operational stress while on mission. Scouten WT , Mehalick ML , Yoder E , McCoy A , Brannock T , Riddle MS . The epidemiology of operation stress during Continuing Promise 2011: a humanitarian response and disaster relief mission aboard a US Navy hospital ship. Prehosp Disaster Med. 2017;32(4):393-402.}, } @article {pmid28306557, year = {2017}, author = {Rai, R and Sidhom, M and Lim, K and Ohanessian, L and Liney, GP}, title = {MRI micturating urethrography for improved urethral delineation in prostate radiotherapy planning: a case study.}, journal = {Physics in medicine and biology}, volume = {62}, number = {8}, pages = {3003-3010}, doi = {10.1088/1361-6560/62/8/3003}, pmid = {28306557}, issn = {1361-6560}, mesh = {Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Prostatic Neoplasms/diagnostic imaging/*radiotherapy ; Radiosurgery/methods ; Radiotherapy Planning, Computer-Assisted/*methods ; Urethra/diagnostic imaging ; }, abstract = {Stereotactic ablative body radiotherapy is used in prostate cancer to deliver a high dose of radiation to the tumour over a small number of treatments. This involves the simulation of the patient using both CT and MRI. Current practice is to insert an indwelling catheter (IDC) during CT to assist with visualisation of the urethra and subsequently minimise dose to this highly critical structure. However, this procedure is invasive and has an associated risk of infection. This is a case study, which demonstrates our initial experience of using a real-time non-invasive MRI technique to replace the use of IDC for prostate cancer patients. The patient was scanned on a dedicated 3T MRI and was instructed to micturate in their own time whereupon a sagittal T2 weighted HASTE sequence was acquired every 5 s. This was subsequently followed by T2 weighted axial imaging at the level of mid prostate to provide improved urethral definition. Acquired images showed bladder voidance in real-time and an increase in signal intensity in the proximal urethra post voiding allowing for delineation of the urethra. The dimension and shape of the proximal urethra was well visualised and accumulation time of urine in the urethra was sufficient to enable optimum timing of the scanning technique. We have presented for the first time a micturating urethography technique using MRI, which has allowed us to visualise the urethra without contrast and with minimal invasiveness to the patient.}, } @article {pmid28303378, year = {2017}, author = {Altundag, K}, title = {Pure invasive lobular carcinoma versus mixed invasive lobular cancer and invasive ductal carcinoma: metastatic patterns differ?.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {24}, number = {6}, pages = {795}, doi = {10.1007/s12282-017-0769-9}, pmid = {28303378}, issn = {1880-4233}, mesh = {*Breast Neoplasms ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular ; Humans ; Retrospective Studies ; }, } @article {pmid28301465, year = {2017}, author = {Chao, LF and Singh, M and Thompson, J and Yates, JR and Hagstrom, KA}, title = {An SMC-like protein binds and regulates Caenorhabditis elegans condensins.}, journal = {PLoS genetics}, volume = {13}, number = {3}, pages = {e1006614}, pmid = {28301465}, issn = {1553-7404}, support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/growth & development ; Caenorhabditis elegans Proteins/classification/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Meiosis/genetics ; Microscopy, Confocal ; Mitosis/genetics ; Multiprotein Complexes/*genetics/metabolism ; Mutation ; Nuclear Proteins/genetics/metabolism ; Phylogeny ; Protein Binding ; Protein Subunits/genetics/metabolism ; Sequence Homology, Amino Acid ; X Chromosome/genetics ; }, abstract = {Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics.}, } @article {pmid28299890, year = {2017}, author = {Oba, T and Maeno, K and Ono, M and Iesato, A and Ito, T and Kanai, T and Mochizuki, Y and Ito, KI and Yoshizawa, A and Takayama, F}, title = {A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of [18] F-Fluorodeoxyglucose on a Positron Emission Tomography.}, journal = {The breast journal}, volume = {23}, number = {2}, pages = {220-224}, doi = {10.1111/tbj.12715}, pmid = {28299890}, issn = {1524-4741}, mesh = {Adenomyoepithelioma/*diagnostic imaging/surgery ; Aged ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/surgery ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Mastectomy, Segmental ; Positron-Emission Tomography/*methods ; Radiopharmaceuticals/pharmacokinetics ; Sentinel Lymph Node Biopsy ; Ultrasonography, Mammary ; }, abstract = {An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through [18] F-fluorodeoxyglucose positron emission tomography (FDG-PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73-year-old woman presented to our hospital with a 3.5-cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5-cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG-PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.}, } @article {pmid28299888, year = {2017}, author = {Guth, AA and Chun Kim, J and Schwartz, S and Montes, J and Snyder, RA and Axelrod, D and Schnabel, F}, title = {The Relationship of Race, Oncotype DX, and Ki67 in a Population Highly Screened For Breast Cancer.}, journal = {The breast journal}, volume = {23}, number = {2}, pages = {177-181}, doi = {10.1111/tbj.12781}, pmid = {28299888}, issn = {1524-4741}, mesh = {Adult ; Black or African American ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Cohort Studies ; Female ; Humans ; Ki-67 Antigen/analysis/*metabolism ; Mammography ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Receptor, ErbB-2/metabolism ; Triple Negative Breast Neoplasms/diagnosis/pathology ; White People ; Young Adult ; }, abstract = {Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi-Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college-level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African-Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African-Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki-67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.}, } @article {pmid28296665, year = {2018}, author = {Boufelli, G and Giannotti, MA and Ruiz, CA and Barros, N and Chala, LF and Maesaka, JY and Goncalves, R and Bresciani, BH and Vianna, P and Soares, JM and Baracat, EC and Filassi, JR}, title = {Papillomas of the breast: factors associated with underestimation.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {27}, number = {4}, pages = {310-314}, pmid = {28296665}, issn = {1473-5709}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Papillary/*diagnosis/diagnostic imaging/surgery ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Mammography/*methods ; Middle Aged ; Prognosis ; Risk Assessment/*methods ; Risk Factors ; Ultrasonography, Mammary/*methods ; }, abstract = {The distinction between benign and malignant papilloma of the breast through percutaneous needle biopsy can be difficult because of limited samples; the underestimation rate can be up to 25%. The aim of this study is to identify clinical and histological factors associated with underestimation, invasive ductal carcinoma, or ductal in-situ carcinoma (DCIS) of the breast found in surgical specimens from papillary lesions. This may contribute toward selection of patients for a follow-up strategy without the need for surgical excision. From a database of 3563 patients, we identified 85 with intraductal papilloma between 2007 and 2013 who had undergone breast-imaging studies, percutaneous needle biopsy, and surgical resection of the lesion. Central papillomas normally present with a palpable mass, whereas peripheral papillomas generally do not have clinical manifestations (microcalcifications); both central and peripheral papillomas were related to atypical lesions, 13.5 and 15.4%, respectively. Among the 59 cases of central papillomas, there were four cases of underestimation, three DCIS and one invasive ductal carcinoma (6.8%). Among the 26 cases of peripheral papillomas, there was one case of DCIS (3.8%), with a total underestimation rate of 5.8%; all underestimated lesions measured more than 1 cm. The median size was 11 mm at mammography and 19 mm at ultrasound. Our data suggest that lesions less than 1 cm in size, without atypia and concordant imaging and clinical findings, may not require surgical resection.}, } @article {pmid28292362, year = {2017}, author = {Lateef, F and Jamal, S and Nasir, S and Jamil, Z}, title = {Invasive Ductal Carcinoma: Correlation of Immunophenotypic Features with Age.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {27}, number = {1}, pages = {18-22}, pmid = {28292362}, issn = {1681-7168}, mesh = {Adult ; Age Factors ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology/surgery ; Cross-Sectional Studies ; Female ; Humans ; Immunophenotyping/methods ; Mastectomy/methods ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Assessment ; Survival Analysis ; }, abstract = {OBJECTIVE: To evaluate the frequency of hormone receptors and Her2neu expression and their correlation with age in patients of carcinoma breast.

STUDY DESIGN: Descriptive, cross-sectional study.

PLACE AND DURATION OF STUDY: Department of Histopathology, Dr. Ziauddin Hospital, Karachi, between the period 2006 - 2013.

METHODOLOGY: Estrogen receptors, progesterone receptors and Her2neu immunohistochemical staining was performed on all specimens of carcinoma breast of female patients. Allred scoring was followed using normal epithelium as internal control. Age was determined in years. Results were described as percentages.

RESULTS: Three hundred and forty-six cases of infiltrating ductal carcinoma of breast between the age of 20 - 90 years (mean= 49 ±14 years) were studied. Seventy-nine (23%) cases were below the age of 40 years. ER +ve cases were 210 (61%), PR +ve were 190 (55%), and 78 (23%) were Her2neu +ve. Three were 12 (3%) triple positive cases and 58 (17%) triple negative cases. One hundred and seven (31%) cases were ER/PR+ve and Her2neu -ve. Most of the breast cancer cases were aged between 41 - 50 years. Estrogen receptor positivity was maximum between 41 - 60 years. Fifty percent cases of carcinoma breast below 30-year age were also ER positive.

CONCLUSION: A high proportion of breast cancer in young Pakistani females is alarming. Younger age harbours aggressive clinicopathologic characteristics. There is a due need for identifying high risk individuals/families including BRCA1 and BRCA2 testings, biologically driven trials devoted specifically to this group.}, } @article {pmid28292084, year = {2016}, author = {Khalil, AI and Bendahhou, K and Mestaghanmi, H and Saile, R and Benider, A}, title = {[Synchronous bilateral breast cancer: experiences in the Mohammed VI Cancer Treatment Center, CHU Ibn Rochd, Casablanca].}, journal = {The Pan African medical journal}, volume = {25}, number = {}, pages = {121}, pmid = {28292084}, issn = {1937-8688}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*pathology/therapy ; Contraceptives, Oral/administration & dosage ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Morocco ; Neoplasms, Multiple Primary/*pathology/therapy ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {Synchronous bilateral breast cancers (SBBC) are characterized by extensive clinical and morphological heterogeneity, with an frequency between 1.5 and 3.2%. Women treated for unilateral breast cancer are at higher risk of developing contralateral breast cancer. Screening and advances in breast imaging have improved detection rates of SBBC. Our study aims to analyze the epidemiological, clinical, histological and therapeutic features of bilateral breast cancer. We conducted a cross-sectional study of patients with breast cancer treated at the Mohammed VI Center over a two year period. Statistical analysis of the results was performed using R. software. 31 patients had SBBC, representing 2.4% of breast cancer cases in our Center. The average age was 47.8 ± 8.4 years, 22.6% of patients used oral contraceptives. A family history of breast cancer was observed in 22.6% of cases. The most common histological type was invasive ductal carcinoma (58.1%), SBR grade II and III were common (38.7%). Hormone receptors were positive for progesterone (38.7%) and for estrogen (41.9%). HER2 was overexpressed in 20.0% of cases. 29.0% of patients received hormonal therapy and 3.2% targeted therapies. Our study showed that bilateral breast cancer represents a small percentage of all breast cancers but have specific clinical features that help to differentiate it from unilateral breast cancer.}, } @article {pmid28292037, year = {2016}, author = {Khalil, AI and Bendahhou, K and Mestaghanmi, H and Saile, R and Benider, A}, title = {[Breast cancer in Morocco: phenotypic profile of tumors].}, journal = {The Pan African medical journal}, volume = {25}, number = {}, pages = {74}, pmid = {28292037}, issn = {1937-8688}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology/therapy ; Breast Neoplasms, Male/epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*pathology/therapy ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Neoplasm Staging ; Phenotype ; Young Adult ; }, abstract = {Breast cancer is most common in women and it is among the leading causes of cancer related deaths. The curability of this type of tumor is increasing thanks to screening programs and treatment advances which have certainly enhanced patient survival. But challenges remain, particularly in respect of phenotypic instability of cancer cells. The aim of this study was to analyse the phenotypic profile of breast cancer in patients treated at Mohammed VI Cancer Treatment Center over the years 2013-2014. We conducted a cross-sectional study over a two-year period, including the cases of breast cancer treated in our Center. Data were collected from patients medical records and analyzed using Epi Info software. 1277 patients were treated in our Center. 99.5% were females, mean age 50.20 ± 11.34 years. The most common histological type was invasive ductal carcinoma (80.7% of cases). It was diagnosed at an early stage (56,9%). The most common molecular phenotype was luminal A (41.4% of cases). Luminal B, HER2 and triple negatives occurred in 10.4%, 6.3%, 11.2% of cases respectively. The study of tumor phenotype in patients with breast cancer helps clinician make treatment choice and policy makers implement programs against this disease.}, } @article {pmid28291966, year = {2017}, author = {Miyazaki, T and Ohishi, Y and Miyasaka, Y and Oda, Y and Aishima, S and Ozono, K and Abe, A and Nagai, E and Nakamura, M and Oda, Y}, title = {Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {84}, number = {4}, pages = {192-201}, doi = {10.1159/000455194}, pmid = {28291966}, issn = {1423-0291}, mesh = {Aged ; Carcinoma in Situ/*complications ; Carcinoma, Pancreatic Ductal/complications/*genetics/metabolism/*pathology ; Humans ; Middle Aged ; Pancreas/metabolism/pathology ; Pancreatic Neoplasms/complications/*genetics/metabolism/pathology ; Prognosis ; Proto-Oncogene Proteins p21(ras)/*genetics ; Smad4 Protein/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIMS: We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN.

METHOD AND RESULTS: We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: the PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40). We evaluated the p53, p16, and SMAD4 expressions in the invasive ductal carcinoma (IDC) components by immunohistochemical staining. KRAS mutation was also analyzed in 80 tumors. The PanIN-low group showed significantly more frequent "high p53 expression" and "loss of SMAD4 expression" than the PanIN-high group (p = 0.048 and p = 0.019, respectively). Loss of p16 expression was not significantly different between the groups. The rate of KRAS wild type was significantly higher in the PanIN-low group than the PanIN-high group (p = 0.024).

CONCLUSIONS: Our results demonstrated that the molecular characteristics in the PDACs with high-grade PanIN were different from those in the PDACs without high-grade PanIN. PDACs without high-grade PanIN may develop via a pathway other than the PanIN-carcinoma sequence.}, } @article {pmid28291131, year = {2017}, author = {Konstantinova, AM and Shelekhova, KV and Imyanitov, EN and Iyevleva, A and Kacerovska, D and Michal, M and Kazakov, DV}, title = {Study of Selected BRCA1, BRCA2, and PIK3CA Mutations in Benign and Malignant Lesions of Anogenital Mammary-Like Glands.}, journal = {The American Journal of dermatopathology}, volume = {39}, number = {5}, pages = {358-362}, doi = {10.1097/DAD.0000000000000725}, pmid = {28291131}, issn = {1533-0311}, mesh = {Aged ; Aged, 80 and over ; Anus Neoplasms/genetics/pathology ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Biopsy, Needle ; Class I Phosphatidylinositol 3-Kinases/*genetics ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mammary Glands, Human/pathology ; Middle Aged ; Mutation ; Paget Disease, Extramammary/*genetics/*pathology ; Prognosis ; Retrospective Studies ; Risk Assessment ; Vulvar Neoplasms/genetics/pathology ; }, abstract = {Anogenital mammary-like glands (AGMLGs) are nowadays considered a normal component of the anogenital area. Lesions involving AGMLGs are histopathologically very similar to their mammary counterparts, but the information on molecular biological mechanisms in these vulvar/perianal tumors is scarce. Mutations in the PI3K-AKT cascade have been found in hidradenoma papilliferum. The authors studied selected BRCA1, BRCA2, and PIK3CA mutations in series of benign and malignant neoplasms thought to be associated with AGMLGs, including 9 cases of primary extramammary Paget disease, 3 different cases of mammary-type carcinoma (adenoid cystic like, tubulolobular, and invasive ductal like), and 5 cases of hidradenoma papilliferum. No BRCA mutation was detected, whereas 3 neoplasms yielded PIK3CA mutation, including extramammary Paget disease, mammary-type invasive ductal carcinoma, and tubulolobular carcinoma. Our study expands the spectrum of lesions of AGMLGs harboring mutations in genes encoding the PI3K-AKT cascade. Further studies of the whole BRCA1 and BRCA2 genes using a larger cohort are needed to clarify their role in the pathogenesis of AGMLG lesions.}, } @article {pmid28289662, year = {2017}, author = {Nam, MJ and Kim, BC and Park, SC and Hong, CW and Han, KS and Sohn, DK and Park, WS and Chang, HJ and Oh, JH}, title = {Mucosa-Associated Lymphoid-Tissue Lymphoma of the Cecum and Rectum: A Case Report.}, journal = {Annals of coloproctology}, volume = {33}, number = {1}, pages = {35-38}, pmid = {28289662}, issn = {2287-9714}, abstract = {A colonic mucosa-associated lymphoid-tissue (MALT) lymphoma is relatively rare compared to lymphomas of the stomach or small intestine. We present a case of a MALT lymphoma in the cecum and rectum found during screening colonoscopy. A 54-year-old female, who had undergone right-breast-conserving surgery with axillary dissection due to an invasive ductal carcinoma and a left-breast excisional biopsy due to microcalcification following adjuvant chemoradiation therapy 3 years earlier, was found to have 3-mm-sized smooth elevated lesions in both the cecum and rectum. No pathologic lesion or lymphadenopathy was found at any other site, but chronic gastritis negative for Helicobacter pylori infection was found. The polyps were removed by using an endoscopic biopsy and revealed an extra nodal marginal zone B-cell MALT lymphoma, showing positive for CD3 and CD20 by immunohistochemical staining. The patient underwent close observation without any additional treatment and has shown no evidence of recurrence as of her last visit.}, } @article {pmid28288473, year = {2017}, author = {Min, KW and Kim, DH and Do, SI and Chae, SW and Kim, K and Sohn, JH and Lee, HJ and Do, IG and Pyo, JS and Kim, Y and Kim, DH and Yang, JH and Lee, SJ and Oh, YH and Oh, S and Choi, SH and Park, YL and Park, CH and Kim, EK and Kwon, MJ and Seo, J}, title = {Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {84}, number = {3}, pages = {130-138}, doi = {10.1159/000449428}, pmid = {28288473}, issn = {1423-0291}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Disease-Free Survival ; Female ; GATA3 Transcription Factor/*metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Prognosis ; Smad4 Protein/*metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer.

METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed.

RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+.

CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.}, } @article {pmid28274688, year = {2017}, author = {Li, X and Lu, P and Li, B and Zhang, W and Yang, R and Chu, Y and Luo, K}, title = {Interleukin 2 and interleukin 10 function synergistically to promote CD8[+] T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer.}, journal = {The international journal of biochemistry & cell biology}, volume = {87}, number = {}, pages = {1-7}, pmid = {28274688}, issn = {1878-5875}, mesh = {Breast Neoplasms/immunology/*pathology ; CD4 Antigens/metabolism ; CD4-Positive T-Lymphocytes/*cytology/*drug effects/immunology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Synergism ; Female ; Humans ; Interleukin-10/*pharmacology ; Interleukin-2/*pharmacology ; Interleukin-2 Receptor alpha Subunit/metabolism ; Middle Aged ; T-Lymphocytes, Regulatory/*cytology/*drug effects/immunology/metabolism ; }, abstract = {The precise role of interleukin (IL)-10 in breast cancer is not clear. Previous studies suggested a tumor-promoting role of IL-10 in breast cancer, whereas recent discoveries that IL-10 activated and expanded tumor-resident CD8[+] T cells challenged the traditional view. Here, we investigated the role of IL-10 in HLA-A2-positive breast cancer patients with Grade III, Stage IIA or IIB in-situ and invasive ductal carcinoma, and compared it with that of IL-2, the canonical CD8[+] T cell growth factor. We first observed that breast cancer patients presented higher serum levels of IL-2 and IL-10 than healthy controls. Upon prolonged TCR stimulation, peripheral blood CD8[+] T cells from breast cancer patients tended to undergo apoptosis, which could be prevented by the addition of IL-2 and/or IL-10. The cytotoxicity of TCR-activated CD8[+] T cells was also enhanced by exogenous IL-2 and/or IL-10. Interestingly, IL-2 and IL-10 demonstrated synergistic effects, since the enhancement in CD8[+] T cell function when both cytokines were added was greater than the sum of the improvements mediated by each individual cytokine. IL-10 by itself could not promote the proliferation of CD8[+] T cells but could significantly enhance IL-2-mediated promotion of CD8[+] T cell proliferation. In addition, the cytotoxicity of tumor-infiltrating CD8[+] T cells in breast tumor was elevated when both IL-2 and IL-10 were present but not when either one was absent. This synergistic effect was stopped by CD4[+]CD25[+] regulatory T cells (Treg), which depleted IL-2 in a cell number-dependent manner. Together, these results demonstrated that IL-2 and IL-10 could work synergistically to improve the survival, proliferation, and cytotoxicity of activated CD8[+] T cells, an effect suppressible by CD4[+]CD25[+] Treg cells.}, } @article {pmid28273747, year = {2017}, author = {Park, GE and Kim, SH and Kim, EJ and Kang, BJ and Park, MS}, title = {Histogram analysis of volume-based apparent diffusion coefficient in breast cancer.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {58}, number = {11}, pages = {1294-1302}, doi = {10.1177/0284185117694507}, pmid = {28273747}, issn = {1600-0455}, mesh = {Adult ; Aged ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Diagnosis, Differential ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; *Tumor Burden ; }, abstract = {Background Breast cancer is a heterogeneous disease. Recent studies showed that apparent diffusion coefficient (ADC) values have various association with tumor aggressiveness and prognosis. Purpose To evaluate the value of histogram analysis of ADC values obtained from the whole tumor volume in invasive ductal cancer (IDC) and ductal carcinoma in situ (DCIS). Material and Methods This retrospective study included 201 patients with confirmed DCIS (n = 37) and IDC (n = 164). The IDC group was divided into two groups based on the presence of a DCIS component: IDC-DCIS (n = 76) and pure IDC (n = 88). All patients underwent preoperative breast magnetic resonance imaging (MRI) with diffusion-weighted images at 3.0 T. Histogram parameters of cumulative ADC values, skewness, and kurtosis were calculated and statistically analyzed. Results The differences between DCIS, IDC-DCIS, and pure IDC were significant in all percentiles of ADC values, in descending order of DCIS, IDC-DCIS, and pure IDC. IDC showed significantly lower ADC values than DCIS, and ADC50 was the best indicator for discriminating IDC from DCIS, with a threshold of 1.185 × 10[-3] mm[2]/s (sensitivity of 82.9%, specificity of 75.7%). However, multivariate analysis of obtained ADC values showed no significant differences between DCIS, IDC-DCIS, and pure IDC (P > 0.05). Conclusion Volume-based ADC values showed association with heterogeneity of breast cancer. However, there was no additional diagnostic performance in histogram analysis for differentiating between DCIS, IDC-DCIS, and pure IDC.}, } @article {pmid28272456, year = {2017}, author = {Zhang, J and Naik, HS and Assefa, T and Sarkar, S and Reddy, RV and Singh, A and Ganapathysubramanian, B and Singh, AK}, title = {Computer vision and machine learning for robust phenotyping in genome-wide studies.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {44048}, pmid = {28272456}, issn = {2045-2322}, mesh = {*Artificial Intelligence ; Genome-Wide Association Study/*methods ; Image Processing, Computer-Assisted ; *Machine Learning ; Phenotype ; Quantitative Trait Loci ; Soybeans/*genetics/metabolism ; Stress, Physiological ; }, abstract = {Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.}, } @article {pmid28264146, year = {2017}, author = {Yao, X and Gan, Y and Chang, E and Hibshoosh, H and Feldman, S and Hendon, C}, title = {Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT.}, journal = {Lasers in surgery and medicine}, volume = {49}, number = {3}, pages = {258-269}, pmid = {28264146}, issn = {1096-9101}, support = {DP2 HL127776/HL/NHLBI NIH HHS/United States ; }, mesh = {Biopsy, Needle ; Breast/*diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Cross-Sectional Studies ; Female ; Humans ; *Imaging, Three-Dimensional ; Immunohistochemistry ; In Vitro Techniques ; Mastectomy/methods ; Reference Values ; Sampling Studies ; Tomography, Optical Coherence/*methods ; }, abstract = {BACKGROUND AND OBJECTIVE: Breast cancer is one of the most common cancers, and recognized as the third leading cause of mortality in women. Optical coherence tomography (OCT) enables three dimensional visualization of biological tissue with micrometer level resolution at high speed, and can play an important role in early diagnosis and treatment guidance of breast cancer. In particular, ultra-high resolution (UHR) OCT provides images with better histological correlation. This paper compared UHR OCT performance with standard OCT in breast cancer imaging qualitatively and quantitatively. Automatic tissue classification algorithms were used to automatically detect invasive ductal carcinoma in ex vivo human breast tissue.

Human breast tissues, including non-neoplastic/normal tissues from breast reduction and tumor samples from mastectomy specimens, were excised from patients at Columbia University Medical Center. The tissue specimens were imaged by two spectral domain OCT systems at different wavelengths: a home-built ultra-high resolution (UHR) OCT system at 800 nm (measured as 2.72 μm axial and 5.52 μm lateral) and a commercial OCT system at 1,300 nm with standard resolution (measured as 6.5 μm axial and 15 μm lateral), and their imaging performances were analyzed qualitatively. Using regional features derived from OCT images produced by the two systems, we developed an automated classification algorithm based on relevance vector machine (RVM) to differentiate hollow-structured adipose tissue against solid tissue. We further developed B-scan based features for RVM to classify invasive ductal carcinoma (IDC) against normal fibrous stroma tissue among OCT datasets produced by the two systems. For adipose classification, 32 UHR OCT B-scans from 9 normal specimens, and 28 standard OCT B-scans from 6 normal and 4 IDC specimens were employed. For IDC classification, 152 UHR OCT B-scans from 6 normal and 13 IDC specimens, and 104 standard OCT B-scans from 5 normal and 8 IDC specimens were employed.

RESULTS: We have demonstrated that UHR OCT images can produce images with better feature delineation compared with images produced by 1,300 nm OCT system. UHR OCT images of a variety of tissue types found in human breast tissue were presented. With a limited number of datasets, we showed that both OCT systems can achieve a good accuracy in identifying adipose tissue. Classification in UHR OCT images achieved higher sensitivity (94%) and specificity (93%) of adipose tissue than the sensitivity (91%) and specificity (76%) in 1,300 nm OCT images. In IDC classification, similarly, we achieved better results with UHR OCT images, featured an overall accuracy of 84%, sensitivity of 89% and specificity of 71% in this preliminary study.

CONCLUSION: In this study, we provided UHR OCT images of different normal and malignant breast tissue types, and qualitatively and quantitatively studied the texture and optical features from OCT images of human breast tissue at different resolutions. We developed an automated approach to differentiate adipose tissue, fibrous stroma, and IDC within human breast tissues. Our work may open the door toward automatic intraoperative OCT evaluation of early-stage breast cancer. Lasers Surg. Med. 49:258-269, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28263858, year = {2017}, author = {Miller, PR and Chang, MC and Hoth, JJ and Hildreth, AN and Wolfe, SQ and Gross, JL and Martin, RS and Carter, JE and Meredith, JW and D'Agostino, R}, title = {Predicting Mortality and Independence at Discharge in the Aging Traumatic Brain Injury Population Using Data Available at Admission.}, journal = {Journal of the American College of Surgeons}, volume = {224}, number = {4}, pages = {680-685}, doi = {10.1016/j.jamcollsurg.2016.12.053}, pmid = {28263858}, issn = {1879-1190}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Brain Injuries, Traumatic/*diagnosis/*mortality ; Databases, Factual ; *Decision Support Techniques ; Female ; Humans ; Independent Living/*statistics & numerical data ; Logistic Models ; Male ; Middle Aged ; Patient Admission/statistics & numerical data ; Patient Discharge/statistics & numerical data ; Prognosis ; Retrospective Studies ; United States/epidemiology ; Wounds, Nonpenetrating/*diagnosis/*mortality ; }, abstract = {BACKGROUND: Aging worsens outcome in traumatic brain injury (TBI), but available studies may not provide accurate outcomes predictions due to confounding associated injuries. Our goal was to develop a predictive tool using variables available at admission to predict outcomes related to severity of brain injury in aging patients.

STUDY DESIGN: Characteristics and outcomes of blunt trauma patients, aged 50 or older, with isolated TBI, in the National Trauma Data Bank (NTDB), were evaluated. Equations predicting survival and independence at discharge (IDC) were developed and validated using patients from our trauma registry, comparing predicted with actual outcomes.

RESULTS: Logistic regression for survival and IDC was performed in 57,588 patients using age, sex, Glasgow Coma Scale score (GCS), and Revised Trauma Score (RTS). All variables were independent predictors of outcome. Two models were developed using these data. The first included age, sex, and GCS. The second substituted RTS for GCS. C statistics from the models for survival and IDC were 0.90 and 0.82 in the GCS model. In the RTS model, C statistics were 0.80 and 0.67. The use of GCS provided better discrimination and was chosen for further examination. Using a predictive equation derived from the logistic regression model, outcome probabilities were calculated for 894 similar patients from our trauma registry (January 2012 to March 2016). The survival and IDC models both showed excellent discrimination (p < 0.0001). Survival and IDC generally decreased by decade: age 50 to 59 (80% IDC, 6.5% mortality), 60 to 69 (82% IDC, 7.0% mortality), 70 to 79 (76% IDC, 8.9% mortality), and 80 to 89 (67% IDC, 13.4% mortality).

CONCLUSIONS: These models can assist in predicting the probability of survival and IDC for aging patients with TBI. This provides important data for loved ones of these patients when addressing goals of care.}, } @article {pmid28260832, year = {2016}, author = {Pugh, J and Douglas, T}, title = {Justifications for Non-Consensual Medical Intervention: From Infectious Disease Control to Criminal Rehabilitation.}, journal = {Criminal justice ethics}, volume = {35}, number = {3}, pages = {205-229}, pmid = {28260832}, issn = {0731-129X}, support = {100705/WT_/Wellcome Trust/United Kingdom ; }, abstract = {A central tenet of medical ethics holds that it is permissible to perform a medical intervention on a competent individual only if that individual has given informed consent to the intervention. Yet it occasionally seems morally permissible to carry out non-consensual medical interventions on competent individuals for the purpose of infectious disease control (IDC). We describe two different moral frameworks that have been invoked in support of non-consensual IDC interventions and identify five desiderata that might be used to guide assessments of the moral permissibility of such interventions on either kind of fundamental justification. We then consider what these desiderata imply for the justifiability of carrying out non-consensual medical interventions that are designed to facilitate rehabilitation amongst serious criminal offenders. We argue that these desiderata suggest that a plausible case can be made in favor of such interventions.}, } @article {pmid28259217, year = {2017}, author = {Baer, L and Rogers, SC and Farrelly, P and Tornos, C and Sweeney, K}, title = {The First Case of HER2+ Invasive Ductal Carcinoma Arising From a Breast Hamartoma and Literature Review.}, journal = {Journal of the National Medical Association}, volume = {109}, number = {1}, pages = {55-59}, doi = {10.1016/j.jnma.2016.10.002}, pmid = {28259217}, issn = {0027-9684}, mesh = {Breast/diagnostic imaging ; *Breast Diseases/diagnosis/metabolism ; *Breast Neoplasms/diagnosis/metabolism/pathology ; *Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology ; Female ; *Hamartoma/diagnosis/metabolism/pathology ; Humans ; Mammography/methods ; Middle Aged ; Molecular Targeted Therapy/*methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Precision Medicine/methods ; Prognosis ; *Receptor, ErbB-2/analysis/antagonists & inhibitors ; }, abstract = {Carcinomas arising from breast hamartomas are exceedingly rare. We present the first reported case of an African-American female presenting with a right breast lump and a subsequent mammogram suggestive of a hamartoma. She later underwent lumpectomy and was found to have HER2+ invasive ductal carcinoma (IDC) arising from a hamartoma. She was amenable to HER2-targeted trastuzumab, hormone therapy and adjuvant radiation but declined chemotherapy. In a review of the literature, IDC is the predominant neoplastic type found in hamartomas. The average hamartoma size at time of neoplasm diagnosis is 6.0 cm. Patients with hamartomas greater than 6.0 cm, with changes in calcification pattern; new nodules or asymmetry should be considered for additional evaluation with ultrasound, MRI and/or biopsy. HER2 status is under-reported among cases and should be evaluated in any malignancy found within hamartomas as HER-2 therapy has improved overall survival and recurrence free survival in HER2+breast cancer patients.}, } @article {pmid28250861, year = {2017}, author = {Lee, SS and Bae, SK and Park, YS and Park, JS and Kim, TH and Yoon, HK and Ahn, HJ and Lee, SM}, title = {Correlation of Molecular Subtypes of Invasive Ductal Carcinoma of Breast with Glucose Metabolism in FDG PET/CT: Based on the Recommendations of the St. Gallen Consensus Meeting 2013.}, journal = {Nuclear medicine and molecular imaging}, volume = {51}, number = {1}, pages = {79-85}, pmid = {28250861}, issn = {1869-3474}, abstract = {PURPOSE: This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013.

METHODS: Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUVmax was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics.

RESULTS: The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUVmax in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUVmax differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUVmax to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively.

CONCLUSION: The SUVmax showed a significant correlation with the molecular subtype. Although SUVmax measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUVmax.}, } @article {pmid28240942, year = {2017}, author = {Zwebner, Y and Sellier, AL and Rosenfeld, N and Goldenberg, J and Mayo, R}, title = {We look like our names: The manifestation of name stereotypes in facial appearance.}, journal = {Journal of personality and social psychology}, volume = {112}, number = {4}, pages = {527-554}, doi = {10.1037/pspa0000076}, pmid = {28240942}, issn = {1939-1315}, mesh = {Adult ; Facial Recognition/*physiology ; Female ; France ; Humans ; Israel ; Male ; *Names ; *Social Perception ; *Stereotyping ; Young Adult ; }, abstract = {Research demonstrates that facial appearance affects social perceptions. The current research investigates the reverse possibility: Can social perceptions influence facial appearance? We examine a social tag that is associated with us early in life-our given name. The hypothesis is that name stereotypes can be manifested in facial appearance, producing a face-name matching effect, whereby both a social perceiver and a computer are able to accurately match a person's name to his or her face. In 8 studies we demonstrate the existence of this effect, as participants examining an unfamiliar face accurately select the person's true name from a list of several names, significantly above chance level. We replicate the effect in 2 countries and find that it extends beyond the limits of socioeconomic cues. We also find the effect using a computer-based paradigm and 94,000 faces. In our exploration of the underlying mechanism, we show that existing name stereotypes produce the effect, as its occurrence is culture-dependent. A self-fulfilling prophecy seems to be at work, as initial evidence shows that facial appearance regions that are controlled by the individual (e.g., hairstyle) are sufficient to produce the effect, and socially using one's given name is necessary to generate the effect. Together, these studies suggest that facial appearance represents social expectations of how a person with a specific name should look. In this way a social tag may influence one's facial appearance. (PsycINFO Database Record}, } @article {pmid28240797, year = {2017}, author = {Durhan, G and Öztekin, PS and Ünverdi, H and Değirmenci, T and Durhan, A and Karakaya, J and Nercis Koşar, P and Necip Köseoğlu, E and Hücümenoğlu, S}, title = {Do Histopathological Features and Microcalcification Affect the Elasticity of Breast Cancer?.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {36}, number = {6}, pages = {1101-1108}, doi = {10.7863/ultra.16.06064}, pmid = {28240797}, issn = {1550-9613}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/*physiopathology ; Calcinosis/*diagnostic imaging/*pathology/physiopathology ; Elastic Modulus ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Mammography/*methods ; Middle Aged ; Neoplasm Grading ; Observer Variation ; Reproducibility of Results ; Sensitivity and Specificity ; Stress, Mechanical ; }, abstract = {OBJECTIVES: The aim of this study was to evaluate any association between histological grade, molecular subtypes of breast cancer, and strain elastography, and to investigate whether microcalcification affects the stiffness of tumor in breast cancers with the same histological grade.

METHODS: Between April 2015 and March 2016, 94 lesions of 94 patients with the diagnosis of invasive ductal carcinoma were included in the study. Strain elastography was performed on all patients before biopsy. Histological grades (Grades 1, 2, and 3), molecular subtypes (luminal A, luminal B, Her-2, and basal-like), and strain ratio (SR) were compared. In the same histological grades, patients were divided into two groups according to the presence of microcalcifications, and the groups were compared with each other.

RESULTS: Compared with Grades 1 (20.5) and 2 (23.7), Grade 3 (11.7) showed lower SR values (Grade 3-2, P = .01; Grade 3-1, P = .2). The groups with microcalcification had slightly higher SR in all histological grades, but not of statistical significance. In molecular subtypes, luminal A and B demonstrated higher SR, whereas HER2 and basal-like had lower SR (P > .05 for all group comparisons).

CONCLUSIONS: Grade 3 invasive ductal carcinomas are different from other grades with lower SR values. The presence of microcalcifications and molecular subtypes do not affect elasticity like a high histological grade does.}, } @article {pmid28240424, year = {2017}, author = {Saeter, T and Vlatkovic, L and Waaler, G and Servoll, E and Nesland, JM and Axcrona, K and Axcrona, U}, title = {Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.}, journal = {The Prostate}, volume = {77}, number = {8}, pages = {859-865}, doi = {10.1002/pros.23326}, pmid = {28240424}, issn = {1097-0045}, mesh = {Aged ; *Biopsy, Needle/methods/statistics & numerical data ; *Carcinoma, Intraductal, Noninfiltrating/mortality/pathology ; Disease Progression ; Humans ; Male ; Medical Records, Problem-Oriented/statistics & numerical data ; Mortality ; Neoplasm Grading ; Neoplasm Staging ; Norway/epidemiology ; *Prostate/diagnostic imaging/pathology ; Prostatectomy/methods ; *Prostatic Neoplasms/mortality/pathology ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality.

MATERIALS AND METHODS: This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality.

RESULTS: Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis.

CONCLUSION: IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors facilitate carcinoma invasion to the prostatic acini and ducts. Prostate 77:859-865, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28240310, year = {2017}, author = {Sowrirajan, B and Saito, Y and Poudyal, D and Chen, Q and Sui, H and DeRavin, SS and Imamichi, H and Sato, T and Kuhns, DB and Noguchi, N and Malech, HL and Lane, HC and Imamichi, T}, title = {Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47[phox].}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {43441}, pmid = {28240310}, issn = {2045-2322}, support = {HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation/drug effects ; Dendritic Cells/cytology/*drug effects/immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Interleukins/*pharmacology ; Macrophage Activation/drug effects ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/cytology/*drug effects/immunology ; NADPH Oxidases/*genetics/immunology ; Phosphorylation/drug effects ; Primary Cell Culture ; Signal Transduction ; Superoxide Dismutase/genetics/immunology ; Superoxides/immunology/*metabolism ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27. Real time PCR, western blot and knock down assays demonstrate that IL-27 is able to enhance the potential of superoxide production not only during differentiation but also in terminally differentiated-macrophages and immature dendritic cells (iDC) in association with the induction of p47[phox], a cytosolic component of the ROS producing enzyme, NADPH oxidase, and the increase in amounts of phosphorylated p47[phox] upon stimulation. We also demonstrate that IL-27 is able to induce extracellular superoxide dismutase during differentiation of monocytes but not in terminal differentiated macrophages. Since ROS plays an important role in a variety of inflammation, our data demonstrate that IL-27 is a potent regulator of ROS induction and may be a novel therapeutic target.}, } @article {pmid28239564, year = {2016}, author = {Lo, PK and Wolfson, B and Zhou, Q}, title = {Cancer stem cells and early stage basal-like breast cancer.}, journal = {World journal of obstetrics and gynecology}, volume = {5}, number = {2}, pages = {150-161}, pmid = {28239564}, issn = {2218-6220}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; }, abstract = {Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment. However, there are no available targeted therapies for patients with basal-like DCIS (BL-DCIS) tumors due to their frequent lack of endocrine receptors and HER2 amplification, rendering them potentially susceptible to recurrence. Moreover, multiple lines of evidence suggest that DCIS is a non-obligate precursor of invasive breast carcinoma. This raises the possibility that targeting precursor BL-DCIS is a promising strategy to prevent BL-DCIS patients from the development of invasive basal-like breast cancer. An accumulating body of evidence demonstrates the existence of cancer stem-like cells (CSCs) in BL-DCIS, which potentially determine the features of BL-DCIS and their ability to progress into invasive cancer. This review encompasses the current knowledge in regard to the characteristics of BL-DCIS, identification of CSCs, and their biological properties in BL-DCIS. We summarize recently discovered relevant molecular signaling alterations that promote the generation of CSCs in BL-DCIS and the progression of BL-DCIS to invasive breast cancer, as well as the influence of the tissue microenvironment on CSCs and the invasive transition. Finally, we discuss the translational implications of these findings for the prognosis and prevention of BL-DCIS relapse and progression.}, } @article {pmid28233285, year = {2017}, author = {Yamamoto, Y and Nakamura, T and Koyama, H and Kanai, T and Moritani, S and Ichihara, S}, title = {Sebaceous carcinoma of the breast: a case report.}, journal = {Surgical case reports}, volume = {3}, number = {1}, pages = {38}, pmid = {28233285}, issn = {2198-7793}, abstract = {BACKGROUND: Sebaceous carcinoma of the breast is a distinct variant of invasive ductal carcinoma. It is rare and only several cases have been reported.

CASE PRESENTATION: An 80-year-old woman noted bloody discharge from her left nipple and palpated a lump in her left breast. Ultrasonography revealed a 19-mm mass in the left breast. Fine-needle aspiration suggested invasive ductal carcinoma. Partial mastectomy and sentinel lymph node biopsy were performed. On histological examination, the tumor revealed solid growth of small, round uniform cells with clear cytoplasm, partially intermingled with vacuolated cells indicative of sebaceous differentiation. The tumor cells contained abundant Sudan Black B-positive lipid droplets in the cytoplasm, and they were immunohistochemically positive for adipophilin. They were negative for estrogen receptor, progesterone receptor, and androgen receptor; positive for cytokeratin 7 and Ber-EP4; and partially positive for epithelial membrane antigen. Based on these findings, the patient was diagnosed with sebaceous carcinoma of the breast.

CONCLUSIONS: We diagnosed a rare case of sebaceous carcinoma of the breast.}, } @article {pmid28224328, year = {2017}, author = {Santangelo, G and Lagravinese, G and Battini, V and Chiorri, C and Siciliano, M and Abbruzzese, G and Vitale, C and Barone, P}, title = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {38}, number = {5}, pages = {845-853}, pmid = {28224328}, issn = {1590-3478}, mesh = {Adult ; Age Factors ; Aged ; Cognition Disorders/*diagnosis/*etiology ; Educational Status ; Female ; Healthy Volunteers ; Humans ; Italy ; Male ; Middle Aged ; *Neuropsychological Tests ; Parkinson Disease/*complications ; Reference Values ; Severity of Illness Index ; Young Adult ; }, abstract = {The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson's disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30-79 years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.}, } @article {pmid28222936, year = {2017}, author = {Wang, S and Li, W and Wang, F and Niu, Y and Hao, C and Wang, X and He, L and Tong, Z}, title = {36 cases adenoid cystic carcinoma of the breast in China: Comparison with matched grade one invasive ductal carcinoma-not otherwise specified.}, journal = {Pathology, research and practice}, volume = {213}, number = {4}, pages = {310-315}, doi = {10.1016/j.prp.2017.01.021}, pmid = {28222936}, issn = {1618-0631}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Adenoid Cystic/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; China ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristic of adenoid cystic carcinoma (ACC).

MATERIALS AND METHODS: The clininopathological features, along with relapse free survival(RFS) and overall survival(OS) of 36 patients with ACC were retrospectively investigated and compared with those of 108 grade 1 invasive ductal carcinoma not-otherwise-specified (G1-IDC-NOS) patients.

RESULTS: Most cases of ACC were ER, PR and HER-2 negative which was classified as triple-negative subtype. Five cases were concomitant with other pathological types of cancer. Axillary lymph node dissection(ALND) was performed in 31 patients and 2 of them with lymph nodes metastasis. Two patients died of lung metastases at 46 and 116 months after the surgery respectively. Compared with G1-IDC-NOS, ACC showed lower Ki-67 index, less lymph nodes metastasis, lower P53 expression, and higher proportion in location of upper outer quadrant of breast. There was no difference of OS and RFS between ACC and G1-IDC-NOS.

CONCLUSIONS: ACC of the breast was a rare disease with a good prognosis although most of them were classified as triple-negative subtype. And the value of axillary node dissection and adjuvant therapy needs to be further investigated.}, } @article {pmid28220963, year = {2017}, author = {Benatov, J and Nakash, O and Chen-Gal, S and Brunstein Klomek, A}, title = {The Association Between Gender, Ethnicity, and Suicidality Among Vocational Students in Israel.}, journal = {Suicide & life-threatening behavior}, volume = {47}, number = {6}, pages = {647-659}, doi = {10.1111/sltb.12332}, pmid = {28220963}, issn = {1943-278X}, mesh = {Adolescent ; Anxiety/epidemiology/psychology ; Depression/epidemiology/psychology ; *Ethnicity ; Female ; Humans ; Israel/epidemiology ; Male ; Self Report ; Sex Factors ; Students/*psychology ; *Suicidal Ideation ; Suicide, Attempted/psychology ; *Vocational Education ; Young Adult ; }, abstract = {Gender and ethnicity are significant factors when evaluating suicidal risk, especially among ethnically diverse populations. In the current study we explored the association between gender, ethnicity, and suicide ideation and attempts among Arab and Jewish vocational education and training high school students in Israel. Students (N = 3,554) completed a self-report survey evaluating suicide ideation and attempts, depression, anxiety, somatization, and sense of belonging. Hierarchical generalized linear modeling indicated that female Arab adolescents had elevated levels of suicide ideation, higher rates of suicide attempts, and greater psychological distress than Arab males and Jewish students. Furthermore, female Arab adolescents were found to be more susceptible to suicide ideation when depression levels were high. These results are discussed in the context of the double-jeopardy Arab young women face, as members of a minority ethnic group in Israel and their status as women within the patriarchal Arab culture.}, } @article {pmid28214265, year = {2017}, author = {Picillo, M and Santangelo, G and Erro, R and Cozzolino, A and Amboni, M and Vitale, C and Barone, P and Pellecchia, MT}, title = {Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {37}, number = {}, pages = {106-110}, doi = {10.1016/j.parkreldis.2017.02.010}, pmid = {28214265}, issn = {1873-5126}, mesh = {Aged ; Anxiety/diagnostic imaging/*etiology ; Chi-Square Distribution ; Cohort Studies ; Cross-Sectional Studies ; Dopamine/*metabolism ; Dopamine Plasma Membrane Transport Proteins/*metabolism ; Female ; Humans ; International Cooperation ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnostic imaging/*metabolism ; Psychiatric Status Rating Scales ; Statistics as Topic ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {OBJECTIVES: To explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC).

METHODS: This is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan. Relationships between neuropsychiatric symptoms and DAT uptakes were analysed by means of stepwise multiple regression analysis.

RESULTS: In the PD group, lower DAT uptake in the right caudate was associated with higher STAI trait subscore (β = -2.939, 95%CI: -4.634 to -1.254, p = 0.001). Depression and apathy scores were not related with DAT uptakes. No associations were found in the HC group.

CONCLUSIONS: Our cross-sectional analysis of the PPMI data shows that lower caudate DAT uptake is associated with higher level of anxiety. The data strengthens the relationship between dopaminergic dysfunction and neuropsychiatric symptoms in early PD.}, } @article {pmid28212138, year = {2017}, author = {Becker, AS and Marcon, M and Ghafoor, S and Wurnig, MC and Frauenfelder, T and Boss, A}, title = {Deep Learning in Mammography: Diagnostic Accuracy of a Multipurpose Image Analysis Software in the Detection of Breast Cancer.}, journal = {Investigative radiology}, volume = {52}, number = {7}, pages = {434-440}, doi = {10.1097/RLI.0000000000000358}, pmid = {28212138}, issn = {1536-0210}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted/*methods ; *Machine Learning ; Mammography/*methods ; Middle Aged ; Prevalence ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of a multipurpose image analysis software based on deep learning with artificial neural networks for the detection of breast cancer in an independent, dual-center mammography data set.

MATERIALS AND METHODS: In this retrospective, Health Insurance Portability and Accountability Act-compliant study, all patients undergoing mammography in 2012 at our institution were reviewed (n = 3228). All of their prior and follow-up mammographies from a time span of 7 years (2008-2015) were considered as a reference for clinical diagnosis. After applying exclusion criteria (missing reference standard, prior procedures or therapies), patients with the first diagnosis of a malignoma or borderline lesion were selected (n = 143). Histology or clinical long-term follow-up served as reference standard. In a first step, a breast density-and age-matched control cohort was selected (n = 143) from the remaining patients with more than 2 years follow-up (n = 1003). The neural network was trained with this data set. From the publicly available Breast Cancer Digital Repository data set, patients with cancer and a matched control cohort were selected (n = 35 × 2). The performance of the trained neural network was also tested with this external data set. Three radiologists (3, 5, and 10 years of experience) evaluated the test data set. In a second step, the neural network was trained with all cases from January to September and tested with cases from October to December 2012 (screening-like cohort). The radiologists also evaluated this second test data set. The areas under the receiver operating characteristic curve between readers and the neural network were compared. A Bonferroni-corrected P value of less than 0.016 was considered statistically significant.

RESULTS: Mean age of patients with lesion was 59.6 years (range, 35-88 years) and in controls, 59.1 years (35-83 years). Breast density distribution (A/B/C/D) was 21/59/42/21 and 22/60/41/20, respectively. Histologic diagnoses were invasive ductal carcinoma in 90, ductal in situ carcinoma in 13, invasive lobular carcinoma in 13, mucinous carcinoma in 3, and borderline lesion in 12 patients. In the first step, the area under the receiver operating characteristic curve of the trained neural network was 0.81 and comparable on the test cases 0.79 (P = 0.63). One of the radiologists showed almost equal performance (0.83, P = 0.17), whereas 2 were significantly better (0.91 and 0.94, P < 0.016). In the second step, performance of the neural network (0.82) was not significantly different from the human performance (0.77-0.87, P > 0.016); however, radiologists were consistently less sensitive and more specific than the neural network.

CONCLUSIONS: Current state-of-the-art artificial neural networks for general image analysis are able to detect cancer in mammographies with similar accuracy to radiologists, even in a screening-like cohort with low breast cancer prevalence.}, } @article {pmid28208155, year = {2017}, author = {Catalano, OA and Horn, GL and Signore, A and Iannace, C and Lepore, M and Vangel, M and Luongo, A and Catalano, M and Lehman, C and Salvatore, M and Soricelli, A and Catana, C and Mahmood, U and Rosen, BR}, title = {PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.}, journal = {British journal of cancer}, volume = {116}, number = {7}, pages = {893-902}, pmid = {28208155}, issn = {1532-1827}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Fluorodeoxyglucose F18/metabolism ; Follow-Up Studies ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Multimodal Imaging/methods ; Neoplasm Staging ; Phenotype ; Positron-Emission Tomography/*methods ; Prognosis ; Radiopharmaceuticals/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes.

METHODS: 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA.

RESULTS: ER/PR- tumours demonstrated higher Kepmean and SUVmax than ER or PR+ tumours. HER2- tumours displayed higher ADCmean, Kepmean, and SUVmax than HER2+tumours. Only ADCmean discriminated Ki67⩽14% tumours (lower ADCmean) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001).

CONCLUSIONS: Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.}, } @article {pmid28207532, year = {2017}, author = {Zhong, J and Lei, J and Jiang, K and Li, Z and Gong, R and Zhu, J}, title = {Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review.}, journal = {Medicine}, volume = {96}, number = {7}, pages = {e6114}, pmid = {28207532}, issn = {1536-5964}, mesh = {Breast Neoplasms/*complications/pathology/surgery ; Carcinoma/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/*complications/pathology/surgery ; Carcinoma, Papillary ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/*complications/pathology/surgery ; Thyroidectomy ; }, abstract = {BACKGROUND: The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years).

CASE SUMMARY: The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer.

CONCLUSION: Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases.}, } @article {pmid28203454, year = {2016}, author = {Saberi, A and Danyaei, A and Neisi, N and Dastoorpoor, M and Tahmasbi Birgani, MJ}, title = {MiR-328 May be Considered as an Oncogene in Human Invasive Breast Carcinoma.}, journal = {Iranian Red Crescent medical journal}, volume = {18}, number = {11}, pages = {e42360}, pmid = {28203454}, issn = {2074-1804}, abstract = {BACKGROUND: The recent investigations have rendered microRNAs (miRs) as a novel biomarker in cancer research. In fact, alteration in miR expression may be associated with tumor suppression, tumorigenesis, metastasis, and poor prognosis in human breast cancer (BC).

OBJECTIVES: The aim of this clinical experimental study was to measure the miR-328 expression level in breast cancer tissues, at first. Then, we tried to find out any possible correlation between miR-328 and prognostic and predictive biomarkers in BC. Both of these two objectives were investigated for the first time; and we did not find any similar survey measuring the expression level of miR-328 in both tumor and non-tumor breast tissues. This research was conducted in Iran (Ahvaz, Khuzestan), between December 2013 and April 2014. Furthermore, we did not find any previous document investigating the correlation between miR-328 expression level and prognostic factors in BC. Due to the lack of similar studies intending to measure the expression level of miR-328 in tumor and adjacent non-tumor tissues, we decided to carry out a pilot study.

METHODS: We measured the expression level of miR-328 by Poly (A) real-time PCR based on SYBR Green-I in 28 fresh samples of BC tissues and 28 samples of normal adjacent tissues, including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). We tried to attribute the results to clinicopathologic features such as status of estrogen and progesterone receptors (ER/PR), HER2/neu (HER2), P53 and also Ki67 labeling (Ki67-LI).

RESULTS: The results showed that the miR-328 median level of expression was 0.88 (2[-ΔΔCt]) (25[th]-75[th] percentile, 0.07 - 2.34). It means that the expression level increased in tumor tissues compared to normal adjacent tissues (NATs). However, a statistically significant correlation between the miR-328 median expression level and prognostic factors, including pathologic diagnosis, age, and also the status of ER, PR, HER2, and Ki67-LI was not observed (P > 0.05).

CONCLUSIONS: Therefore, it might be possible to consider miR-328 as an oncogene; but not necessarily an oncomiR, in human BC.}, } @article {pmid28198519, year = {2017}, author = {Jeong, YJ and Jung, JW and Cho, YY and Park, SH and Oh, HK and Kang, S}, title = {Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.}, journal = {Nuclear medicine review. Central & Eastern Europe}, volume = {20}, number = {1}, pages = {32-38}, doi = {10.5603/NMR.a2016.0043}, pmid = {28198519}, issn = {1644-4345}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnostic imaging/*metabolism/mortality ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Middle Aged ; Molecular Imaging/methods ; Positron Emission Tomography Computed Tomography/methods/statistics & numerical data ; Prevalence ; Radiopharmaceuticals/pharmacokinetics ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Tumor Hypoxia ; }, abstract = {BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.

MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.

RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).

CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.}, } @article {pmid28195257, year = {2016}, author = {Nottegar, A and Luchini, C and Cingarlini, S and Beccari, S and Grego, E and Gilioli, E and Manfrin, E and Bonetti, F}, title = {Pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies: a case report and review of the literature.}, journal = {Pathologica}, volume = {108}, number = {4}, pages = {164-168}, pmid = {28195257}, issn = {0031-2983}, mesh = {Adenocarcinoma/*pathology/therapy ; Adenocarcinoma of Lung ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Female ; Humans ; Lung Neoplasms/*pathology/therapy ; Middle Aged ; *Neoplasms, Multiple Primary ; Treatment Outcome ; }, abstract = {A pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects.}, } @article {pmid28192852, year = {2018}, author = {Ein-Dor, T and Perry-Paldi, A and Merrin, J and Efrati, Y and Hirschberger, G}, title = {Effective Disengagement: Insecure People Are More Likely to Disengage From an Ongoing Task and Take Effective Action When Facing Danger.}, journal = {Journal of personality}, volume = {86}, number = {2}, pages = {233-246}, doi = {10.1111/jopy.12308}, pmid = {28192852}, issn = {1467-6494}, mesh = {Adolescent ; Adult ; Anxiety/*psychology ; Attention ; Avoidance Learning ; *Dangerous Behavior ; *Defense Mechanisms ; *Fear ; Female ; Humans ; Israel ; Male ; Middle Aged ; Motivation ; *Object Attachment ; Psychological Theory ; Self Report ; *Social Behavior ; Survival/psychology ; Young Adult ; }, abstract = {OBJECTIVE: People believe that they can respond effectively to threats, but actually they experience difficulties in disengaging from ongoing tasks and shifting their attention to life-threatening events. We contend that this tendency is especially true for secure people with respect to their worldview and perception of others and not for insecure individuals.

METHOD: In Study 1 (N = 290), we examined individuals' reactions to various threat scenarios. In Study 2 (N = 65), we examined these reactions using a behavioral design high in ecological validity. In Study 3 (N = 78), we examined group-level benefits for the actions of insecure individuals by manipulating asocial behavior in response to an emergency.

RESULTS: Study 1 indicated that anxiously attached individuals stayed away from threats and sought help; avoidant people tended to take action by either assessing the risk of the event and/or enacting an asocial action such as fight or flight. Study 2 added ecological validity to these findings, and Study 3 showed that priming asocial behavior responses promoted actions that increased group members' chances of survival.

CONCLUSION: Results validate the central tenets of social defense theory and indicate that actions that are deemed asocial may paradoxically promote the survival of individuals and groups.}, } @article {pmid28191801, year = {2016}, author = {Naveed, S and Quari, H and Panjawani, G and Shah, A and Panday, BB}, title = {Evaluation of Clinicopathological Findings on 255 cases of Inoperable Locally Advanced Breast Carcinoma: A Tertiary Care Experience.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {22}, pages = {16-20}, pmid = {28191801}, issn = {2078-2101}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology/*therapy ; Carcinoma/*pathology/*therapy ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; *Tertiary Healthcare ; }, abstract = {INTRODUCTION: Breast cancer is the second most common cancer in the Indian female population. LABC and metastatic breast cancer are the most common stages at presentation in most low-resource countries. Although the incidence of LABC has decreased significantly in countries with enhanced resources thanks to widespread education and screening programs, it remains a daily encounter for surgeons and oncologists in low-resource countries. Neoadjuvant therapy has been studied widely for the treatment of LABC and is followed by locoregional therapy.

OBJECTIVES: As per our hospital data, breast cancer is also found to be the second leading malignancy in women and locally advanced breast cancer is the most common type of breast cancer. Hence, we undertook this study to evaluate the clinical profile, histopathologic types and grade of the disease in our patients.

MATERIALS AND METHODS: This study was undertaken over a period of three years comprising of 255 patients who underwent modified radical mastectomy following neoadjuvant chemotherapy after preliminary diagnosis of carcinoma on histopathological examination of the trucut biopsy specimens. Clinicopathological evaluation was done in all of these cases following standard protocols.

RESULTS: The study comprised of 252 female patients and 3 male patients in the age range of 26 to 70 years. Majority (255, 66.6%) of the cases were within the age range of 31‑60 years. Three females had bilateral breast cancer. Invasive ductal carcinoma no special type was the most common histopathologic pattern, and was seen in 254 (98.4%) cases. Most tumors were Scarff Bloom Richardson grade II and American Joint Committee on Cancer pathologic stage 3.

CONCLUSIONS: The present study has provided information about the clinicopathological aspects of locally advanced breast cancer in patients who are from rural areas. LABC remains a daily encounter and challenge for medical and surgical oncologists in developing low-resource countries. Neoadjuvant chemotherapy is recommended for inoperable LABC at all resource levels.}, } @article {pmid28188401, year = {2017}, author = {Walter, H}, title = {[Research domain criteria (RDoC) : Psychiatric research as applied cognitive neuroscience].}, journal = {Der Nervenarzt}, volume = {88}, number = {5}, pages = {538-548}, pmid = {28188401}, issn = {1433-0407}, mesh = {Biomedical Research/*organization & administration ; Cognitive Neuroscience/*methods/*organization & administration ; *Diagnostic and Statistical Manual of Mental Disorders ; Germany ; *Models, Organizational ; Patient Care Team/*organization & administration ; Psychiatry/*organization & administration ; Research Design ; }, abstract = {BACKGROUND: Just before the official launch of the DSM-5 in 2013, the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health was made public and is becoming increasingly more important in psychiatric research.

OBJECTIVE: The aim of this paper is to clarify the conceptual approach of RDoC, to systematically discuss limitations, to present exemplary RDoC-based studies and to consider the relevance of the RDoC concepts for clinicians and scientists.

MATERIAL AND METHODS: The is a qualitative introduction and review article with a critical discussion.

RESULTS AND DISCUSSION: The RDoC initiative was not conceived as an alternative diagnostic manual to DSM-5 or IDC-10/11 for use in clinical practice. It is a new systematic framework for psychiatric research based on the most recent results of cognitive neuroscience and aims to map mental disorders dimensionally and transdiagnostically. Despite some weaknesses, it is currently the most elaborated and scientifically grounded approach for multidisciplinary research on mental disorders. In contrast to the purely symptom-based DSM and ICD approaches, which are agnostic with respect to the pathogenesis of mental diseases, the explicit aim of the RDoC initiative is to systematize biological knowledge about risk factors and causes of mental disorders; therefore, it has a much greater potential to develop new and individualized therapeutic strategies based on disease mechanisms.}, } @article {pmid28188325, year = {2017}, author = {Lemarignier, C and Martineau, A and Teixeira, L and Vercellino, L and Espié, M and Merlet, P and Groheux, D}, title = {Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with [18]F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {44}, number = {7}, pages = {1145-1154}, pmid = {28188325}, issn = {1619-7089}, mesh = {Adult ; Aged ; Biological Transport ; Breast Neoplasms/*diagnostic imaging/*metabolism/pathology/therapy ; Cohort Studies ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; *Positron Emission Tomography Computed Tomography ; Receptors, Estrogen/*metabolism ; *Tumor Burden ; }, abstract = {PURPOSE: The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC).

METHODS: 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an [18]F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test.

RESULTS: Spearman's coefficients between SUVmax and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUVmax and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast).

CONCLUSIONS: The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUVmax and TLG were able to predict response to NAC, TFs failed.}, } @article {pmid28181469, year = {2017}, author = {Han, B and Du, Y and Fu, T and Fan, Z and Xu, S and Hu, C and Bi, L and Gao, T and Zhang, H and Xu, W}, title = {Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy.}, journal = {Applied spectroscopy}, volume = {71}, number = {2}, pages = {300-307}, doi = {10.1177/0003702816681009}, pmid = {28181469}, issn = {1943-3530}, mesh = {Adult ; Aged ; Breast/*chemistry ; Breast Neoplasms/*chemistry/classification/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/classification/*diagnosis ; Female ; Humans ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrum Analysis, Raman/*methods ; Young Adult ; }, abstract = {The aim of this study was to find the differences and relationships between normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) lesions of the breast based on biochemical characteristics determined by Raman spectroscopy (RS). After collecting 39 frozen sections from patients who underwent surgical resection or mammotome biopsy, nine normal tissues, seven ADH, eight DCIS, and 15 IDC lesions were detected using confocal RS. We then used leave-one-out cross-validation (LOOCV) and radial basis function (RBF) to build a support vector machine (SVM) diagnosis model. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS, and IDC tissues. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The major spectra differences in ADH, DCIS, and IDC spectrograms were evidenced by a red shift with a broad peak of CH2 (1301 cm[-1]), the intensity of the stretching vibration peak of carotenoids (1526 cm[-1]), a relatively strong band of amide-I (1656 cm[-1]), and the nuclear (882 cm[-1]) acid peak. Atypical ductal hyperplasia tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The overall accuracy of SVM model is 74.39%. The sensitivities of normal tissue, ADH, DCIS, and IDC are 62.5%, 50%, 90%, and 66.7%, respectively. The specificities of normal tissue, ADH, DCIS, and IDC are 100%, 100%, 66.7%, and 89.06%, respectively. Atypical ductal hyperplasia shows significant differences and the relationship between normal tissue and malignant disease. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH converts to DCIS and to IDC.}, } @article {pmid28173783, year = {2017}, author = {Effi, AB and Aman, NA and Koui, BS and Koffi, KD and Traoré, ZC and Kouyate, M}, title = {Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: relationship with clinicopathologic factors in 302 patients in Ivory Coast.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {115}, pmid = {28173783}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*metabolism ; Cote d'Ivoire ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Prospective Studies ; Receptors, Estrogen/*analysis/genetics ; Receptors, Progesterone/*analysis/genetics ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous and a hormone-dependent disease. The detection of the estrogen receptor (ER) and progesterone receptor (PgR) is crucial for prognostic evaluation and treatment choice of breast cancer for clinical practice. The purpose of this study was to evaluate the expression of the hormonal receptors, their distribution, and their correlation with clinicopathologic prognostic parameters for the improvement of the patients' treatment in Ivory Coast.

METHODS: The 20-month prospective study included 302 patients who were diagnosed with primary invasive breast carcinomas at the Central Laboratory in Abidjan. The paraffin-embedded blocks of these patients were examined by immunohistochemistry to assess the ER and PgR status. The one-way analysis of variance and Chi-Square Test were used to analyze the data.

RESULTS: The mean age of patients at diagnosis was 48 ± 11 years. The majority of the women were premenopausal in 180 cases (59.9%). The predominant histologic type was invasive ductal carcinoma not otherwise specified (IDC NOS) in 247 cases (82%). Tumor grade 2 was more frequent in 166 cases (55%). Among 302 patients, 169 (56%) and 154 (49%) expressed ER and PgR respectively. The ER+PgR+ group with 131 cases (43%) was predominant, followed by 116 cases (38%) of ER-PgR-. The expression of ER and PgR was correlated with the age of the patients (p = 0.026) and the tumor grade (p = 0.0004). However, there was not statistically significant correlation between ER/PgR and the menopausal status of patients (p = 0.149), nor between ER/PgR and the histologic type (p = 0.523).

CONCLUSION: The ER+PgR+ and ER-PgR- are the most common subgroups in women with breast cancer in Ivory Coast. The hormonal receptor status is associated with the age and the histologic grade in breast cancer patients. The systematic use of hormonal treatment should be reevaluated. A further study should be done to investigate the reasons of high rate of ER-PgR- in breast cancer patients in Ivory Coast.}, } @article {pmid28169235, year = {2016}, author = {Rohilla, M and Bal, A and Singh, G and Joshi, K}, title = {Prediction of heterogeneity in breast cancer immunophenotype at ductal carcinoma in situ stage?.}, journal = {Journal of cancer research and therapeutics}, volume = {12}, number = {4}, pages = {1249-1256}, doi = {10.4103/0973-1482.199541}, pmid = {28169235}, issn = {1998-4138}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Carcinoma In Situ/*diagnosis/genetics/*metabolism ; Breast Neoplasms/*diagnosis/genetics/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Tumor Burden ; Young Adult ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage.

MATERIALS AND METHODS: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors.

RESULTS: DCIS cases were classified as luminal A (46.6% in each group), luminal B (pure DCIS 20% and DCIS component of IDC 13.3%), HER2 overexpressing, basal and nonbasal (pure DCIS 3.3% and 26.6% and DCIS component of IDC 3.3% and 33.3%, respectively), and triple negative, nonbasal (pure DCIS and DCIS component of IDC 3.3% each). The molecular phenotype of DCIS correlated well with that of the coexisting IDC.

CONCLUSIONS: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.}, } @article {pmid28167700, year = {2017}, author = {Zhang, X and Ivanova, A and Vandepoele, K and Radomiljac, J and Van de Velde, J and Berkowitz, O and Willems, P and Xu, Y and Ng, S and Van Aken, O and Duncan, O and Zhang, B and Storme, V and Chan, KX and Vaneechoutte, D and Pogson, BJ and Van Breusegem, F and Whelan, J and De Clercq, I}, title = {The Transcription Factor MYB29 Is a Regulator of ALTERNATIVE OXIDASE1a.}, journal = {Plant physiology}, volume = {173}, number = {3}, pages = {1824-1843}, pmid = {28167700}, issn = {1532-2548}, mesh = {Antimycin A/pharmacology ; Arabidopsis/enzymology/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Gene Regulatory Networks ; Immunoblotting ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/*genetics/metabolism ; Mutation ; Oxidoreductases/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {Plants sense and integrate a variety of signals from the environment through different interacting signal transduction pathways that involve hormones and signaling molecules. Using ALTERNATIVE OXIDASE1a (AOX1a) gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, MYB DOMAIN PROTEIN29 (MYB29) was identified as a negative regulator (regulator of alternative oxidase1a 7 [rao7] mutant) in a genetic screen of Arabidopsis (Arabidopsis thaliana). rao7/myb29 mutants have increased levels of AOX1a transcript and protein compared to wild type after induction with antimycin A. A variety of genes previously associated with the mitochondrial stress response also display enhanced transcript abundance, indicating that RAO7/MYB29 negatively regulates mitochondrial stress responses in general. Meta-analysis of hormone-responsive marker genes and identification of downstream transcription factor networks revealed that MYB29 functions in the complex interplay of ethylene, jasmonic acid, salicylic acid, and reactive oxygen species signaling by regulating the expression of various ETHYLENE RESPONSE FACTOR and WRKY transcription factors. Despite an enhanced induction of mitochondrial stress response genes, rao7/myb29 mutants displayed an increased sensitivity to combined moderate light and drought stress. These results uncover interactions between mitochondrial retrograde signaling and the regulation of glucosinolate biosynthesis, both regulated by RAO7/MYB29. This common regulator can explain why perturbation of the mitochondrial function leads to transcriptomic responses overlapping with responses to biotic stress.}, } @article {pmid28165048, year = {2017}, author = {Johanning, GL and Malouf, GG and Zheng, X and Esteva, FJ and Weinstein, JN and Wang-Johanning, F and Su, X}, title = {Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {41960}, pmid = {28165048}, issn = {2045-2322}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P50 CA100632/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Basal Cell/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Databases, Factual ; Endogenous Retroviruses/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Viral ; Genome, Human ; Humans ; Viral Envelope Proteins/*genetics ; }, abstract = {Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer.}, } @article {pmid28162815, year = {2017}, author = {Roobol, MJ and Verbeek, JFM and van der Kwast, T and Kümmerlin, IP and Kweldam, CF and van Leenders, GJLH}, title = {Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 International Society of Urological Pathology Gleason Grading and Cribriform growth.}, journal = {European urology}, volume = {72}, number = {1}, pages = {45-51}, doi = {10.1016/j.eururo.2017.01.033}, pmid = {28162815}, issn = {1873-7560}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Area Under Curve ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/therapy ; Clinical Decision-Making ; *Decision Support Techniques ; Humans ; Logistic Models ; Male ; Middle Aged ; *Mobile Applications ; Multivariate Analysis ; *Neoplasm Grading ; Patient Selection ; Predictive Value of Tests ; Prostatic Neoplasms/mortality/*pathology/therapy ; ROC Curve ; Reproducibility of Results ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Unnecessary Procedures ; }, abstract = {BACKGROUND: The survival rate for men with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa) without invasive cribriform (CR) and intraductal carcinoma (IDC) is similar to that for ISUP grade 1. If updated into the European Randomized Study of Screening for Prostate Cancer (ERSPC Rotterdam) risk calculator number 3 (RC3), this may further improve upfront selection of men who need a biopsy.

OBJECTIVE: To improve the number of possible biopsies avoided, while limiting undiagnosed clinically important PCa by applying the updated RC3 for risk-based patient selection.

The RC3 is based on the first screening round of the ERSPC Rotterdam, which involved 3616 men. In 2015, histopathologic slides for PCa cases (n=885) were re-evaluated. Low-risk (LR) PCa was defined as ISUP grade 1 or 2 without CR/IDC. High-risk (HR) PCa was defined as ISUP grade 2 with CR/IDC and PCa with ISUP grade≥3.

We updated the RC3 using multinomial logistic regression analysis, including data on age, PSA, digital rectal examination, and prostate volume, for predicting LR and HR PCa. Predictive accuracy was quantified using receiver operating characteristic analysis and decision curve analysis.

RESULTS AND LIMITATIONS: Men without PCa could effectively be distinguished from men with LR PCa and HR PCa (area under the curve 0.70, 95% confidence interval [CI] 0.68-0.72 and 0.92, 95% CI 0.90-0.94). At a 1% risk threshold, the updated calculator would lead to a 34% reduction in unnecessary biopsies, while only 2% of HR PCa cases would be undiagnosed.

CONCLUSIONS: A relatively simple risk stratification tool augmented with a highly sensitive contemporary pathologic biopsy classification would result in a considerable decrease in unnecessary prostate biopsies and overdiagnosis of potentially indolent disease.

PATIENT SUMMARY: We improved a well-known prostate risk calculator with a new pathology classification system that better reflects disease burden. This new risk calculator allows individualized prediction of the chance of having (potentially aggressive) biopsy-detectable prostate cancer and can guide shared decision-making when considering prostate biopsy.}, } @article {pmid28153863, year = {2017}, author = {Ng, CKY and Piscuoglio, S and Geyer, FC and Burke, KA and Pareja, F and Eberle, CA and Lim, RS and Natrajan, R and Riaz, N and Mariani, O and Norton, L and Vincent-Salomon, A and Wen, YH and Weigelt, B and Reis-Filho, JS}, title = {The Landscape of Somatic Genetic Alterations in Metaplastic Breast Carcinomas.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {23}, number = {14}, pages = {3859-3870}, pmid = {28153863}, issn = {1557-3265}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Cadherins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Class I Phosphatidylinositol 3-Kinases/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Metaplasia/*genetics/pathology ; Mutation ; Nuclear Proteins/genetics ; PTEN Phosphohydrolase/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics ; Transcription Factors/genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; Tumor Suppressor Protein p53/genetics ; Exome Sequencing ; Wnt Signaling Pathway/genetics ; }, abstract = {Purpose: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs.Experimental Design: Whole-exome sequencing was performed in 35 MBCs, with 16, 10, and 9 classified as harboring chondroid, spindle, and squamous metaplasia as the predominant metaplastic component. The genomic landscape of MBCs was compared with that of triple-negative invasive ductal carcinomas of no special type (IDC-NST) from The Cancer Genome Atlas. Wnt and PI3K/AKT/mTOR pathway activity was assessed using a qPCR assay.Results: MBCs harbored complex genomes with frequent TP53 (69%) mutations. In contrast to triple-negative IDC-NSTs, MBCs more frequently harbored mutations in PIK3CA (29%), PIK3R1 (11%), ARID1A (11%), FAT1 (11%), and PTEN (11%). PIK3CA mutations were not found in MBCs with chondroid metaplasia. Compared with triple-negative IDC-NSTs, MBCs significantly more frequently harbored mutations in PI3K/AKT/mTOR pathway-related (57% vs. 22%) and canonical Wnt pathway-related (51% vs. 28%) genes. MBCs with somatic mutations in PI3K/AKT/mTOR or Wnt pathway-related genes displayed increased activity of the respective pathway.Conclusions: MBCs are genetically complex and heterogeneous, and are driven by a repertoire of somatic mutations distinct from that of triple-negative IDC-NSTs. Our study highlights the genetic basis and the importance of PI3K/AKT/mTOR and Wnt pathway dysregulation in MBCs and provides a rationale for the metaplastic phenotype and the reported responses to PI3K/AKT/mTOR inhibitors in these tumors. Clin Cancer Res; 23(14); 3859-70. ©2017 AACR.}, } @article {pmid28140614, year = {2017}, author = {Plaza, MJ and Handa, P and Esserman, LE}, title = {Preoperative MRI Evaluation of Axillary Lymph Nodes in Invasive Ductal Carcinoma: Comparison of Luminal A Versus Luminal B Subtypes in a Paradigm Using Ki-67 and Receptor Status.}, journal = {AJR. American journal of roentgenology}, volume = {208}, number = {4}, pages = {910-915}, doi = {10.2214/AJR.15.15788}, pmid = {28140614}, issn = {1546-3141}, mesh = {Axilla ; Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/*pathology/surgery ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Preoperative Care/methods ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node/diagnostic imaging/*pathology ; Treatment Outcome ; }, abstract = {OBJECTIVE: The purpose of this study is to assess whether luminal A versus luminal B molecular subtypes of breast cancer affect the diagnostic utility of preoperative MRI evaluation of the axilla.

MATERIALS AND METHODS: This study identified 125 patients who underwent preoperative breast MRI evaluation of tumors classifiable as luminal A or luminal B molecular subtypes between January 2012 and August 2014. The subtypes were classified on the basis of immunohistochemical staining surrogates combining receptor status and the Ki-67 proliferation index. Statistical analysis was performed using chi-square analysis and one-way ANOVA. When a statistically significant difference was found, follow-up analysis involving pairwise comparison using the Bonferroni correction was performed. Multivariate logistic regression analysis was also used to determine whether the molecular subtype was independently predictive of lymph node involvement.

RESULTS: A total of 80 patients had tumors classifiable as the luminal A molecular subtype, whereas 45 patients had tumors classifiable as the luminal B subtype. Pathologically proven axillary lymph node (ALN) disease occurred statistically significantly more frequently in luminal B tumors (18/45 [40.0%]) than in luminal A tumors (11/80 [13.8%]; p < 0.01). In addition, pathologically proven ALN disease was 4.3 times more likely to occur in luminal B tumors after controlling for patient age, tumor size, and tumor grade (p < 0.01). We found no difference in the negative predictive value of the MRI assessment of the axilla when luminal A tumors were compared with luminal B tumors. The positive predictive value of MRI evaluation of ALNs is statistically significantly higher for luminal B tumors than for luminal A tumors (76.2% vs 28.0%, respectively; p = 0.004).

CONCLUSION: With the use of molecular subtype classification including the Ki-67 proliferation index, suspicious nodes detected in luminal B tumors by MRI are likely to have positive findings and warrant preoperative tissue sampling. Conversely, in view of the high false-positive rate of suspicious nodes detected in luminal A tumors by MRI, proceeding straight to sentinel lymph node biopsy for all cases, except for those with highly suspicious findings, is suggested. These results should, however, be validated in a larger prospective study.}, } @article {pmid28140609, year = {2017}, author = {Huang, ML and Speer, M and Dogan, BE and Rauch, GM and Candelaria, RP and Adrada, BE and Hess, KR and Yang, WT}, title = {Imaging-Concordant Benign MRI-Guided Vacuum-Assisted Breast Biopsy May Not Warrant MRI Follow-Up.}, journal = {AJR. American journal of roentgenology}, volume = {208}, number = {4}, pages = {916-922}, doi = {10.2214/AJR.16.16576}, pmid = {28140609}, issn = {1546-3141}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biopsy, Needle/*methods ; Breast Neoplasms/diagnostic imaging/*pathology ; Female ; Follow-Up Studies ; Humans ; Image-Guided Biopsy/*methods ; Longitudinal Studies ; Magnetic Resonance Imaging, Interventional/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The follow-up of breast lesions with imaging-concordant benign histopathology results on MRI-guided vacuum-assisted biopsy (VAB) is not currently standardized. We determined the false omission rate of breast MRI-guided VAB with benign histopathology (negative results) to assess whether breast MRI follow-up is needed.

MATERIALS AND METHODS: The medical records of patients who underwent 9-gauge breast MRI-guided VAB during 2007-2012 were reviewed retrospectively. Lesions with imaging-concordant benign histopathology results from MRI-guided VAB and surgery or 2 years or more of imaging follow-up were included. The false omission rate (1 - negative predictive value; [number of false-negative results / number of negative results]) of MRI-guided VAB was calculated.

RESULTS: One hundred sixty-nine lesions were included, and 135 had only imaging follow-up (mammography follow-up: range, 17-107 months [median, 52 months]; MRI follow-up: range, 5-95 months [median, 35 months]). Of the 135 lesions with only imaging follow-up, 48 had mammography only (range, 26-86 months; median, 52 months), and 87 had mammography (range, 17-107 months; median, 52 months) and MRI (range, 5-95 months; median, 35 months). Thirty-four lesions had surgical correlation, and there were no cases of imaging-surgical discordance. Four malignancies were later diagnosed in the same breast in which MRI-guided VAB had been performed. One (0.6%) malignancy was invasive ductal carcinoma at 1 cm from the MRI-guided VAB site; it was mammographically detected 24 months after MRI-guided VAB. The other three malignancies developed 4 cm or more from the site of MRI-guided VAB: one ductal carcinoma in situ (DCIS) detected on mammography 12 months after MRI-guided VAB, one DCIS detected on MRI 24 months after MRI-guided VAB, and one Paget disease lesion detected at physical examination 32 months after MRI-guided VAB.

CONCLUSION: Breast MRI-guided VAB has a low false omission rate. MRI follow-up of lesions with concordant benign MRI-guided VAB histopathology results may not be warranted.}, } @article {pmid28139196, year = {2017}, author = {Strandburg-Peshkin, A and Farine, DR and Crofoot, MC and Couzin, ID}, title = {Habitat and social factors shape individual decisions and emergent group structure during baboon collective movement.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28139196}, issn = {2050-084X}, support = {T32 HG003284/HG/NHGRI NIH HHS/United States ; BB/L006081/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Behavior, Animal ; *Decision Making ; *Ecosystem ; *Locomotion ; *Papio ; }, abstract = {For group-living animals traveling through heterogeneous landscapes, collective movement can be influenced by both habitat structure and social interactions. Yet research in collective behavior has largely neglected habitat influences on movement. Here we integrate simultaneous, high-resolution, tracking of wild baboons within a troop with a 3-dimensional reconstruction of their habitat to identify key drivers of baboon movement. A previously unexplored social influence - baboons' preference for locations that other troop members have recently traversed - is the most important predictor of individual movement decisions. Habitat is shown to influence movement over multiple spatial scales, from long-range attraction and repulsion from the troop's sleeping site, to relatively local influences including road-following and a short-range avoidance of dense vegetation. Scaling to the collective level reveals a clear association between habitat features and the emergent structure of the group, highlighting the importance of habitat heterogeneity in shaping group coordination.}, } @article {pmid28133686, year = {2017}, author = {Uçar, FM and Açar, B}, title = {Neutrophil to lymphocyte ratio predicts appropriate therapy in idiopathic dilated cardiomyopathy patients with primary prevention implantable cardioverter defibrillator.}, journal = {Saudi medical journal}, volume = {38}, number = {2}, pages = {143-148}, pmid = {28133686}, issn = {1658-3175}, mesh = {Cardiac Pacing, Artificial/methods ; Cardiomyopathy, Dilated/diagnostic imaging/immunology/*therapy ; *Defibrillators, Implantable/statistics & numerical data ; Echocardiography ; Female ; Humans ; *Leukocyte Count ; *Lymphocyte Count ; Male ; Middle Aged ; *Neutrophils ; Primary Prevention ; Retrospective Studies ; }, abstract = {OBJECTIVES: To investigate whether an inflammatory marker of neutrophil to lymphocyte ratio (NLR) predicts appropriate implantable cardioverter defibrillator (ICD) therapy (shock or anti tachycardia pacing) in idiopathic dilated cardiomyopathy (IDC) patients.

METHODS: We retrospectively examined IDC patients (mean age: 58.3 ± 11.8 years, 81.5% male) with ICD who admitted to outpatient clinic for pacemaker control at 2 tertiary care hospitals in Ankara and Edirne, Turkey from January 2013-2015. All ICDs were implanted for primary prevention. Hematological and biochemical parameters were measured prior procedure. Results: Over a median follow-up period of 43 months (Range 7-125), 68 (33.1%) patients experienced appropriate ICD therapy. The NLR was increased in patients that received appropriate therapy (4.39 ± 2.94 versus 2.96 ± 1.97, p less than 0.001).To identify independent risk factors for appropriate therapy, a multivariate linear regression model was conducted and age (β=0.163, p=0.013), fasting glucose (β=0.158, p=0.017), C-reactive protein (CRP) (β=0.289, p less than 0.001) and NLR (β=0.212, p less than 0.008) were found to be independent risk factors for appropriate ICD therapy. Conclusions: Before ICD implantation by using NLR and CRP, arrhythmic episodes may be predictable and better antiarrhythmic medical therapy optimization may protect these IDC patients from unwanted events.}, } @article {pmid28133285, year = {2016}, author = {Watanabe, M and Enomoto, K and Sakurai, K}, title = {[Primary Breast Cancer in a Man].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {2249-2251}, pmid = {28133285}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Scirrhous/diagnostic imaging/secondary/surgery ; Aged ; Axilla/pathology ; Biopsy, Large-Core Needle ; Breast Neoplasms, Male/diagnostic imaging/*pathology/surgery ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mammography ; Mastectomy ; Neoplasm Invasiveness ; }, abstract = {A 76-year-old man noticed a tumor under his right nipple. Mammography revealed an irregularly shaped nodule in the right breast. Ultrasonography showed a 20mm irregularly shaped nodule in the central area. MRI showed an 18mm irregularly shaped nodule in the central area with skin invasion. On core needle biopsy, the tumor was diagnosed as an invasive ductal carcinoma of the right breast. The patient underwent a mastectomy and axillary lymph node dissection. Histopathologically, the patient was diagnosed with invasive ductal carcinoma(scirrhous carcinoma). The tumor was positive for both ER and PgR, and the HER2 score was 1. The Ki-67 index was 20-30%. Male breast carcinoma accounts for approximately 1.0% of all breast carcinomas. The most common complaint is elastic, hard nodules with no pain. Postoperative therapy for male breast cancer is similar to that for female cancer. This patient underwent a mastectomy and lymph node dissection. After surgery, tamoxifen was administered as adjuvant therapy. There has been no evidence of recurrence for 4 months after the surgery.}, } @article {pmid28133282, year = {2016}, author = {Asano, Y and Kashiwagi, S and Goto, W and Takada, K and Morisaki, T and Takashima, T and Noda, S and Onoda, N and Ohsawa, M and Hirakawa, K and Ohira, M}, title = {[Pathological Complete Response Obtained by Eribulin Chemotherapy in a Case of Advanced Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {2240-2242}, pmid = {28133282}, issn = {0385-0684}, mesh = {Adult ; Biopsy, Fine-Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Female ; Furans/*therapeutic use ; Humans ; Ketones/*therapeutic use ; Lymphatic Metastasis ; Neoadjuvant Therapy ; }, abstract = {A goal for treating advanced disease is prolonging survival while maintaining a good quality of life(QOL). Eribulin chemotherapy may be suitable for this purpose. We report a case of advanced breast cancer with pathological complete response (pCR)obtained by eribulin chemotherapy. The patient was a 43-year-old woman who complained of a right mammary mass. A tumor measuring approximately 3 cm was palpated, and breast cancer was detected via ultrasound examination. Core needle biopsy indicated invasive ductal carcinoma based on histopathological findings. A metastasis to the supraclavicular lymph node was observed and was found to be malignant via fine-needle aspiration cytology. The patient was diagnosed with advanced breast cancer cT2N3M0, stage III C, Luminal B like. She underwent primary systemic therapy with 6 cycles of eribulin. The patient exhibited a clinical complete response to eribulin chemotherapy. Thereafter, a right mastectomy with level 3 axillary lymph node dissection was performed. Pathological diagnosis of the surgical specimen was pCR. At present, 3 years after surgery, the patient has no recurrence.}, } @article {pmid28133220, year = {2016}, author = {Nonomura, A and Aomatsu, N and Tei, S and Haraoka, G and Tsujio, G and Yamakoshi, Y and Wang, E and Nagashima, D and Hirakawa, T and Iwauchi, T and Nishii, T and Morimoto, J and Nakazawa, K and Uchima, Y and Takeuchi, K}, title = {[A Case of HER2-Positive Breast Cancer Treated with Nipple-Sparing Mastectomywith Immediate Reconstruction Using a Tissue Expander after Nab-Paclitaxel Combined with Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {2056-2058}, pmid = {28133220}, issn = {0385-0684}, mesh = {Albumins/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/diagnostic imaging/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*surgery ; Female ; Humans ; Mammaplasty ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Nipples/diagnostic imaging/pathology/*surgery ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/analysis ; Trastuzumab/administration & dosage ; }, abstract = {A 59-year-old woman presented to our hospital with a mass in her left breast. Mammography and ultrasound showed a 9 ×11×12mm mass in her left breast, and left axillary lymph adenopathy. Core needle biopsy and pathological examination confirmed the diagnosis of ER-negative, PgR-negative, HER2-positive invasive ductal carcinoma with axillary lymph metastasis. Dynamic computed tomography(CT)and bone scintigraphy showed no metastasis. A diagnosis ofbreast cancer with stage II A(T1N1M0)was made, and we started neoadjuvant chemotherapy. After 4 cycles of chemotherapy with 5-fluorouracil/ epirubicin/cyclophosphamide in 3-weekly cycles, we administered combination chemotherapy ofnab -paclitaxel and trastuzumab in 3-weekly cycles. After 7 months, the tumor disappeared and the axillary lymph node got significantly smaller. We performed nipple-sparing mastectomy/axillary lymph nodes dissection/tissue-expander placement. The pathological examination ofthe resected tumor confirmed a pathological complete response(pCR). The patient was treated with implant reconstruction and adjuvant therapy. One year has passed after the surgery, and no significant problem has been observed.}, } @article {pmid28133210, year = {2016}, author = {Tokunou, K and Yamamoto, T and Yamamoto, H and Kamei, R and Kitamura, Y and Ando, S}, title = {[A Case of Male Hereditary Breast Cancer Involving a Sentinel Lymph Node Biopsy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {2026-2028}, pmid = {28133210}, issn = {0385-0684}, mesh = {Antineoplastic Agents, Hormonal/therapeutic use ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy/genetics/*pathology/surgery ; Breast Neoplasms, Male/drug therapy/genetics/*pathology/surgery ; Combined Modality Therapy ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Sentinel Lymph Node Biopsy ; Tamoxifen/therapeutic use ; Treatment Outcome ; }, abstract = {We report a rare case of male hereditary breast cancer in which a sentinel lymph node biopsy was performed. A 62-yearold man was admitted to our hospital because of a palpable tumor in his right breast. Both his younger sister and daughter had had breast cancer. Genetic testing revealed a morbid mutation in the BRCA2 gene. The tumor was palpated to an elastic hard mass and had a clear border in the right DCE area. We performed a core needle biopsy and diagnosed invasive ductal carcinoma, specifically, cT1cN0cM0, cStage I hereditary breast cancer. The patient underwent mastectomy and a sentinel lymph node biopsy. Nine days later, tamoxifen therapy was initiated. There has been no sign of recurrence during the 9 months after the operation.}, } @article {pmid28133206, year = {2016}, author = {Hirano, T and Sakurai, K and Fujisaki, S and Adachi, K and Suzuki, S and Masuo, Y and Nagashima, S and Hara, Y and Enomoto, K and Tomita, R and Gonda, K}, title = {[Difficult Decision about a Surgical Margin for a Non-Invasive Apocrine Carcinoma in the Breast - Report of a Case].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {2013-2015}, pmid = {28133206}, issn = {0385-0684}, mesh = {Adult ; Apocrine Glands/diagnostic imaging/pathology/*surgery ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; Female ; Humans ; *Margins of Excision ; Neoplasm Invasiveness ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {We report a case of non-invasive apocrine carcinoma. In this case, we could not identifythe surgical margin. The patient was 39-year-old woman. Micro calcifications were discovered on her right breast during breast cancer screening. Stereotactic vacuum assisted core needle biopsywas performed and the pathological diagnosis was sclerosing adenosis. A low echoic lesion, 26mm in diameter, was discovered in the CDE area of her left breast byultrasonography . A contrast enhanced MRI showed a high intensityarea, 26mm in diameter, on her left breast. Ultrasonographyguided vacuum assisted core needle biopsywas conducted on the low echoic area. The pathological diagnosis was non-invasive ductal carcinoma. We checked her whole bodyand found no metastatic lesion. She underwent breast conserving surgeryplus sentinel lymph node biopsy. We had great difficultyin classifying the surgical margin. The pathological diagnosis from the resected surgical specimen was non-invasive apocrine carcinoma, negative for ER and PgR, and positive for HER2/neu protein expression. The Ki-67 labeling index was 20%, the surgical margins were negative, and the clinical Stage was 0(Tis, N0, M0). She was administered radiation therapy and endocrine therapy as adjuvant therapy. Two years and 6 months after surgery, she is well without metastasis.}, } @article {pmid28133200, year = {2016}, author = {Hashimoto, Y and Sasaki, Y and Yokoyama, S and Yamamoto, Y and Michishita, S and Hirose, H and Nagai, K and Maniwa, T and Ide, Y and Matsuyama, J and Takeda, M and Morimoto, T and Fukushima, Y and Kodama, K}, title = {[A Case of Synchronous Double Cancers of the Liver and Pancreas Treated Using Pancreaticoduodenectomy and Liver Resection].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {1994-1996}, pmid = {28133200}, issn = {0385-0684}, mesh = {Adenocarcinoma/diagnostic imaging/*surgery ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Hepatectomy ; Humans ; Liver Neoplasms/diagnostic imaging/pathology/*surgery ; Middle Aged ; Neoplasms, Multiple Primary/diagnostic imaging/*surgery ; Pancreatic Neoplasms/diagnostic imaging/pathology/*surgery ; Pancreaticoduodenectomy ; }, abstract = {A 50-year-old woman had a 12mm liver tumor at segment 4 and was diagnosed with hemangioma. Two years later, the liver tumor had grown to 27mm in diameter, and a new pancreatic tumor was detected using CT examination. The pancreatic tumor was suspected of being pancreatic carcinoma, based on the results of endoscopic-ultrasound-guided fine-needlebiopsy(EUS-FNA)of the pancreas. The liver tumor was diagnosed as adenocarcinoma using liver biopsy. Because of its slow growth and the solitary liver tumor, synchronous pancreatic cancer and intrahepatic cancer were suspected. We therefore performed pancreaticoduodenectomy with portal vein resection and partial liver resection of segment 4. Upon histological analysis, carcinoma in situ was detected in the liver tumor and the patient was diagnosed with synchronous double cancers of the liver(cholangiocellular carcinoma)and pancreas(invasive ductal carcinoma). Our case indicated that it is very difficult to distinguish cholangiocellular carcinoma from metastatic liver tumor using diagnostic images. We should therefore consider the possibility of cholangiocellular carcinoma when a solitary tumor in the liver is detected at the same time as pancreatic cancer.}, } @article {pmid28133051, year = {2016}, author = {Nakajima, M and Nagahashi, M and Endo, M and Otani, A and Tsuchida, J and Moro, K and Niwano, T and Toshikawa, C and Hasegawa, M and Ikarashi, M and Tatsuda, K and Kameyama, H and Kobayashi, T and Koyama, Y and Wakai, T}, title = {[Study of Breast Cancer Patients Diagnosed Preoperatively with Ductal Carcinoma In Situ].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {1544-1546}, pmid = {28133051}, issn = {0385-0684}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Female ; Humans ; Middle Aged ; Young Adult ; }, abstract = {Although ductal carcinoma in situ(DCIS)is generally cured by surgical resection, it has been suggested that resection is over-treatment for some patients with DCIS. The aim of this study was to reconsider operative indications for patients with DCIS by examining clinicopathological features of 23 patients who underwent surgical resection for DCIS in our institute over a single year. Postoperative histological examination revealed that there were Luminal and HER2-positive subtypes, but no triple negative cancers. We found coincidental invasive ductal carcinoma(IDC)in 5 patients, and in all 5 the tumor size exceeded 60 mm. There was no coincidence of IDC in patients with a Ki-67 index ≤5%. Positive surgical margins were observed in 7 patients, all of which were histologically diagnosed as DCIS. Only 1 of the 7 patients underwent additional surgical resection; the 6 remaining patients, including 2 patients who received no treatment, did not undergo additional resection. All patients including those with positive surgical margins have had a 5-year relapse-free survival. Our findings imply that the subgroup of DCIS patients without IDC could be followed up without surgery.}, } @article {pmid28133023, year = {2016}, author = {Sakakibara, J and Sakakibara, M and Sangai, T and Iwase, T and Nagashima, T}, title = {[Breast-Conserving Surgery Using Real-Time Virtual Sonography in a Breast Cancer Patient Who Received Neoadjuvant Chemotherapy - ACase Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {1461-1463}, pmid = {28133023}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/drug therapy/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Multimodal Imaging ; *Neoadjuvant Therapy ; Time Factors ; Ultrasonography, Mammary ; }, abstract = {We report a case of breast-conserving surgeryusing real-time virtual sonography(RVS)in a breast cancer patient who received neoadjuvant chemotherapy(NAC). The patient was a 63-year-old woman. Ultrasound(US)showed a lobulated 45 ×40×40mm diameter mass in the C area of the right breast. Histological examination found invasive ductal carcinoma that was negative for estrogen and progesterone receptors and for human epidermal growth factor receptor type 2/neu protein expression, and the Ki-67 index was 50%. The patient was diagnosed with breast cancer clinical stage II A(T2N0M0). The basal-like subtype is more sensitive to anthracycline-based NAC than luminal breast cancers. The patient wanted breastconserving surgery. Therefore, we treated the patient with NAC. First, we obtained US volume data of the tumor as a Digital Imaging and Communication in Medicine(DICOM)file, simplyscanning the skin over the lesion gentlywith the probe. We administered tri-weeklynanoparticle albumin-bound paclitaxel(nab PTX)followed bya fluorouracil, epirubicin, and cyclophosphamide(FEC)regimen. Follow-up computed tomography(CT)and US showed good tumor concentric shrinkage without anysurrounding lesion after NAC. Finally, right breast-conserving surgerywas performed, using RVS to detect the area where the tumor was before NAC in the US image after NAC. Histopathologically, the effect of the chemotherapy was Grade 2a and the surgical margins were negative.}, } @article {pmid28133021, year = {2016}, author = {Sakurai, K and Fujisaki, S and Adachi, K and Suzuki, S and Masuo, Y and Nagashima, S and Hara, Y and Hirano, T and Enomoto, K and Tomita, R and Gonda, K}, title = {[Breast Cancer with Microinvasion and Lymph Node Metastasis Diagnosed by Microdochectomy - Report of a Case].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {12}, pages = {1455-1457}, pmid = {28133021}, issn = {0385-0684}, mesh = {Aged ; Biopsy ; Breast Neoplasms/diagnosis/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy, Segmental ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; }, abstract = {We report a case of breast cancer with microinvasion and lymph node metastasis. The patient was a 72-year-old woman who had spontaneous nipple discharge from her left breast. There was no detectable lesion on mammographyor duct endoscopy. Ultrasonography showed a low echoic lesion, 23×15mm in diameter, in the CD area of her left breast. Contrastenhanced MRI showed a high intensityarea, 25mm in diameter, in her left breast, so microdochectomywas performed. The histopathological diagnosis was invasive ductal carcinoma(invasion of 2mm)and the surgical margin was positive. Therefore, she underwent breast conserving surgeryplus axillaryly mph node dissection. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with micro lymph node metastasis, positive for ER and PgR and negative for HER2/neu protein expression. The Ki-67 labeling index was 10% and the surgical margins were negative. She was treated with radiation and endocrine therapy as adjuvant therapy. One year and 6 months after surgery, she was well without metastasis.}, } @article {pmid28124996, year = {2017}, author = {Cha, YJ and Kim, HM and Koo, JS}, title = {Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.}, journal = {International journal of molecular sciences}, volume = {18}, number = {1}, pages = {}, pmid = {28124996}, issn = {1422-0067}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Carcinoma, Lobular/*metabolism/*pathology ; Disease-Free Survival ; Female ; Humans ; *Lipid Metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Prognosis ; }, abstract = {We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p < 0.001) differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001) and perilipin A in luminal A-type IDC (p = 0.007). Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004) and acyl-CoA oxidase 1 positivity (p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.}, } @article {pmid28116205, year = {2016}, author = {Vilaverde, F and Rocha, A and Reis, A}, title = {Tubular Carcinoma of the Breast: Advantages and Limitations of Breast Tomosynthesis.}, journal = {Case reports in radiology}, volume = {2016}, number = {}, pages = {3906195}, pmid = {28116205}, issn = {2090-6862}, abstract = {Tubular carcinoma of the breast is a rare variant of invasive ductal carcinoma. We report a case of 42-year-old asymptomatic female with a histopathological proven multifocal tubular carcinoma, studied by mammography, Tomosynthesis, Ultrasound, and Magnetic Resonance. Herein, we discuss the advantages and limitations of Tomosynthesis, an emerging imaging technique, in this particular case.}, } @article {pmid28111737, year = {2017}, author = {Cha, YJ and Kim, HM and Koo, JS}, title = {Expression of DNA methylation-related proteins in invasive lobular carcinoma of breast: comparison to invasive ductal carcinoma.}, journal = {Histology and histopathology}, volume = {32}, number = {11}, pages = {1175-1185}, doi = {10.14670/HH-11-873}, pmid = {28111737}, issn = {1699-5848}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; *DNA Methylation ; Female ; Humans ; Middle Aged ; }, abstract = {PURPOSE: We aimed to compare the expression of DNA methylation-related proteins in invasive lobular carcinoma (ILC) of breast with those of invasive ductal carcinoma (IDC) of breast and to assess its potential clinical application.

METHODS: Immunohistochemical staining of DNS methylation-related proteins (5-meC, DNMT1, DNMT3B and ISL-1) was applied to tissue microarrays generated from 108 ILCs and 203 IDCs. Protein expression and its correlation with clinicopatholgic variables were statistically analyzed.

RESULTS: ISL-1 and DNMT3B were highly expressed in ILC (p<0.001) and tumoral 5-meC was highly expressed in IDC (p=0.006). DNMT1 (p<0.001) showed higher expression rate in luminal A type ILC. ISL-1 and DNMT3B showed higher expression rate in both luminal A type and luminal B type of ILC (p<0.05). In IDC, tumoral 5-meC commonly showed high positive (p=0.039). On univariate analysis, shorter disease free survival of ILC was associated with DNMT1 high positivity (p=0.001) and ISL-1 positivity (p=0.018).

CONCLUSION: DNA methylation-related proteins are differentially expressed in ILC and IDC, and DNMT1, DNMT3B and ISL-1 show high expression rate in ILC.}, } @article {pmid28110504, year = {2017}, author = {Almeida, SMV and Silva, LPBG and Lima, LRA and Botelho, SPS and Lima, MDC and Pitta, IDR and Beltrão, EIC and Carvalho Júnior, LB}, title = {Dimethyl-2-[(acridin-9-yl)methylidene]-malonate as fluorescent probe for histochemical analysis.}, journal = {Microscopy research and technique}, volume = {80}, number = {6}, pages = {608-614}, doi = {10.1002/jemt.22837}, pmid = {28110504}, issn = {1097-0029}, mesh = {Acridines/*chemistry ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Circular Dichroism ; Concanavalin A/*chemistry ; Female ; Fibroadenoma/*diagnostic imaging ; Fluorescence ; Fluorescent Dyes/*chemistry ; Humans ; Lectins/*analysis ; Malonates/*chemistry ; }, abstract = {Fluorescent compounds have been widely used for biomolecule labeling in cytochemistry and histochemistry analysis. Here, it is described the optical properties of dimethyl 2-[(acridin-9-yl)methylidene]-malonate (LPSF/IP-81), an acridine derivative. This compound was conjugated to Concanavalin A (Con A) lectin and applied as sugar probe in lectin histochemistry. Evaluation of luminescent properties showed that LPSF/IP-81 is photoluminescent with excitation at 360 nm and emission at 428 nm. Con A hemagglutinating activity and LPSF/IP81 photoluminescence were unaltered after conjugation. Circular dichroism of Con A-LPSF/IP81 conjugate showed the maintenance of the Con A structure. Lectin histochemistry with Con A-LPSF/IP81 conjugate demonstrated different pattern recognition studying normal, fibroadenoma, and invasive ductal carcinoma of human breast. These findings indicate that LPSF/IP-81 can be proposed as an alternative probe for histochemical analysis.}, } @article {pmid28108967, year = {2017}, author = {Inoue, M and Nakagomi, H and Nakada, H and Furuya, K and Ikegame, K and Watanabe, H and Omata, M and Oyama, T}, title = {Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {24}, number = {5}, pages = {667-672}, doi = {10.1007/s12282-017-0753-4}, pmid = {28108967}, issn = {1880-4233}, mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Carcinoma, Lobular/drug therapy/mortality/*pathology/secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*epidemiology/pathology/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/mortality/*pathology ; Peritoneal Neoplasms/*epidemiology/pathology/secondary ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial.

METHODS: We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER[+] or PR[+]/HER2[-] subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease.

RESULTS: The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER[+] or PR[+]/HER2[-] subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p < 0.01), while the frequency of peritoneal metastases was significantly higher in the ILC group (68.8%) than in the IDC group (1%) (p = 0.00). Of note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19 ± 9 months and resistance to hormone therapy.

CONCLUSIONS: The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.}, } @article {pmid28105247, year = {2017}, author = {Ayaz, S and Gültekin, SS and Ayaz, ÜY and Dilli, A}, title = {Initial Fludeoxyglucose (18F) Positron Emission Tomography-Computed Tomography (FDG-PET/CT) Imaging of Breast Cancer - Correlations with the Primary Tumour and Locoregional Metastases.}, journal = {Polish journal of radiology}, volume = {82}, number = {}, pages = {9-16}, pmid = {28105247}, issn = {1733-134X}, abstract = {BACKROUND: We aimed to evaluate initial PET/CT features of primary tumour and locoregional metastatic lymph nodes (LNs) in breast cancer and to look for potential relationships between several parameters from PET/CT.

MATERIAL/METHODS: Twenty-three women (mean age; 48.66±12.23 years) with a diagnosis of primary invasive ductal carcinoma were included. They underwent PET/CT imaging for the initial tumour staging and had no evidence of distant metastates. Patients were divided into two groups. The LABC (locally advanced breast cancer) group included 17 patients with ipsilateral axillary lymph node (LN) metastases. The Non-LABC group consisted of six patients without LN metastases. PET/CT parameters including tumour size, axillary LN size, SUVmax of ipsilateral axillary LNs (SUVmax-LN), SUVmax of primary tumour (SUVmax-T) and NT ratios (SUVmax-LN/SUVmax-T) were compared between the groups. Correlations between the above-mentioned PET/CT parameters in the LABC group as well as the correlation between tumour size and SUVmax-T within each group were evaluated statistically.

RESULTS: The mean values of the initial PET/CT parameters in the LABC group were significantly higher than those of the non-LABC group (p<0.05). The correlation between tumour size and SUVmax-T value within both LABC and non-LABC groups was statistically significant (p<0.05). In the LABC group, the correlations between the size and SUVmax-LN values of metastatic axillary LNs, between tumour size and metastatic axillary LN size, between SUVmax-T values and metastatic axillary LN size, between SUVmax-T and SUVmax-LN values, and between tumour size and SUVmax-LN values were all significant (p<0.05).

CONCLUSIONS: We found significant correlations between PET/CT parameters of the primary tumour and those of metastatic axillary LNs. Patients with LN metastases had relatively larger primary tumours and higher SUVmax values.}, } @article {pmid28104032, year = {2017}, author = {Hong, J and Chen, XS and Wu, JY and Huang, O and Zhu, L and He, JR and Fang, Q and Chen, WG and Li, YF and Shen, KW}, title = {[Analysis of the factors influencing adjuvant chemotherapy decisions for triple negative breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {39}, number = {1}, pages = {39-43}, doi = {10.3760/cma.j.issn.0253-3766.2017.01.008}, pmid = {28104032}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Ductal, Breast/*drug therapy/pathology/secondary ; Chemotherapy, Adjuvant/statistics & numerical data ; Consensus ; Cyclophosphamide/administration & dosage ; *Decision Making ; Docetaxel ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Middle Aged ; Paclitaxel/administration & dosage ; Patient Care Team/statistics & numerical data ; Platinum Compounds/administration & dosage ; Retrospective Studies ; Taxoids/administration & dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms/*drug therapy/pathology ; }, abstract = {Objective: To analyze adjuvant chemotherapy decisions for triple negative breast cancer (TNBC), and explore the influencing factors in the multidisciplinary treatment (MDT) modality. Methods: A retrospective analysis was performed. The cases with invasive TNBC who underwent surgery and MDT discussion for adjuvant treatment in Ruijin Hospital, from April 2013 to June 2015, were recruited. The patients' clinicopathological characteristics were analyzed and adjuvant treatment suggestions from MDT were obtained. Here the chemotherapy decision alteration was defined as a disagreement in chemotherapy or not, or inconsistence in regimens between the attending doctor and the multidisciplinary team. Results: A total of 194 patients aged ≤70 years old were enrolled in the multidisciplinary discussion, and 187 patients (96.4%) were suggested to receive chemotherapy. When compared the opinions of the attending doctor to suggestions of the multidisciplinary team, we found that the percentage of chemotherapy decision alteration reached 22.7% (39/172), of which 94.9% (37/39) were inconsistence in chemotherapy regimens. There were 119 patients who were recommended to receive epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) or weekly paclitaxel (wP) regimens. Before the announcement of results for the E1199 trial, EC-T accounted for 62.5% (55/88), and EC-wP accounted for 37.5% (33/88) for this group of patients. After that, the proportion of EC-T was decreased to 22.6% (7/31) and proportion of EC-wP increased to 77.4%(24/31) (P<0.001). In addition, a total of 20 patients were suggested to receive platinum based chemotherapy. The proportions were 9.3% in cases with invasive ductal carcinoma, and 33.3% in cases with metaplastic carcinoma, respectively (P=0.016). Conclusions: The adjuvant chemotherapy decision for TNBC patients is altered in 22.7% of the patients after MDT discussion. After the announcement of SABCS E1199 results, more patients are suggested to receive EC followed by weekly paclitaxel. There is a lack of detailed evidence for platinum based adjuvant chemotherapy for TNBC, and more patients with metaplastic carcinoma receive platinum based adjuvant chemotherapy.}, } @article {pmid28097781, year = {2017}, author = {Felts, JL and Zhu, J and Han, B and Smith, SJ and Truica, CI}, title = {An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.}, journal = {The breast journal}, volume = {23}, number = {6}, pages = {677-686}, doi = {10.1111/tbj.12751}, pmid = {28097781}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*mortality/pathology ; Carcinoma, Lobular/genetics/*mortality/pathology ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Expression Profiling/economics/*methods ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*mortality/pathology ; Neoplasm Staging ; Pennsylvania ; Registries ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated.}, } @article {pmid28090184, year = {2016}, author = {Goyal, S and Verma, P and Raj, SS}, title = {Radiographic Evaluation of the Status of Third Molars in Sriganganagar Population - A Digital Panoramic Study.}, journal = {The Malaysian journal of medical sciences : MJMS}, volume = {23}, number = {6}, pages = {103-112}, pmid = {28090184}, issn = {1394-195X}, abstract = {BACKGROUND: Third molar (M3) agenesis and impaction are associated with evolution, changed dietary habits, and human jaw growth. The aim of the study was to radiographically evaluate the prevalence of M3s agenesis, impacted M3s with different impaction patterns, and the approximation of Inferior Dental Canal (IDC) with impacted mandibular M3s roots among the Sriganganagar population.

METHODS: The study included 700 randomly selected subjects from OPD with an age range of 25-45 years. Digital OPGs were taken for all subjects using Kodak 8000C digital OPG machine. The M3 impaction patterns were evaluated using Winter's classification.

RESULTS: The prevalence of subjects with at least one M3 agenesis was found to be 34.1% and with 95% confidence interval was 30.6% to 37.6%. The overall M3s agenesis was 16.8% with more prevalence in the males. The patients with agenesis of one M3, two M3s, three M3s, and four M3s were 14.4%, 11.3%, 3.7% and 4.7%, respectively. M3 agenesis was more in the upper jaw and on the left side. The total impacted M3s were 21.11% with more prevalence in mixed diet subjects. Mesioangular was most common impaction pattern, and notching was most prevalent IDC relationship with impacted mandibular M3s roots.

CONCLUSION: This study highlighted the evolutionary increasing M3 agenesis and the importance of diagnostic OPG for seeing the status of M3s in jaws.}, } @article {pmid28087477, year = {2017}, author = {Xiao, M and Xu, Q and Lou, C and Qin, Y and Ning, X and Liu, T and Zhao, X and Jia, S and Huang, Y}, title = {Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma.}, journal = {Human pathology}, volume = {62}, number = {}, pages = {40-49}, doi = {10.1016/j.humpath.2016.12.020}, pmid = {28087477}, issn = {1532-8392}, mesh = {Apoptosis Regulatory Proteins/*analysis/genetics ; Biomarkers, Tumor/*analysis/genetics ; Blotting, Western ; Breast Neoplasms/*chemistry/genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/secondary/surgery ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Logistic Models ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Odds Ratio ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome ; Up-Regulation ; }, abstract = {Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.}, } @article {pmid28084531, year = {2017}, author = {Granek, L and Ben-David, M and Nakash, O and Cohen, M and Barbera, L and Ariad, S and Krzyzanowska, MK}, title = {Oncologists' negative attitudes towards expressing emotion over patient death and burnout.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {25}, number = {5}, pages = {1607-1614}, pmid = {28084531}, issn = {1433-7339}, mesh = {Adaptation, Psychological ; Adult ; Attitude ; Burnout, Professional/*psychology ; Emotions/*physiology ; Female ; Humans ; Male ; Medical Oncology/*trends ; Middle Aged ; Oncologists/*psychology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {PURPOSE: The aims of this study were to examine the relationship between negative attitudes towards expressing emotion following patient death and burnout in oncologists and to explore oncologists' preferences for institutional interventions to deal with patient death.

METHODS: The participants included a convenience sample of 177 oncologists from Israel and Canada. Oncologists completed a questionnaire package that included a sociodemographic survey, a burnout measure, a survey assessing negative attitudes towards expressing emotion, and a survey assessing desired interventions to cope with patient death. To examine the association between burnout and negative attitudes while controlling for the effect of sociodemographic variables, a hierarchical linear regression was computed.

RESULTS: Higher burnout scores were related to higher negative attitudes towards perceived expressed emotion (partial r = .25, p < .01) of those who viewed this affect as a weakness and as a sign of unprofessionalism. Approximately half of the oncologists found each of the five categories of institutional interventions (pedagogical strategies, emotional support, group/peer support, taking time off, and research and training) helpful in coping with patient death.

CONCLUSIONS: Our findings suggest that high burnout scores are associated with negative attitudes towards expressing emotion and that there is a wide variation in oncologist preferences in coping with patient death. Institutions should promote interventions that are varied and that focus on the needs of oncologists in order to reduce burnout. Interventions that legitimize expression of emotion about patient death may be useful. Another way to reduce stigma would be to require oncologists to "opt out" rather than "opt in" to accessing a selection of social and/or individual interventions.}, } @article {pmid28078143, year = {2016}, author = {Schnabel, FR and Pivo, S and Chun, J and Schwartz, S and Refinetti, AP and Axelrod, D and Guth, A}, title = {Breast Cancer Profile among Patients with a History of Chemoprevention.}, journal = {International journal of breast cancer}, volume = {2016}, number = {}, pages = {9216375}, pmid = {28078143}, issn = {2090-3170}, abstract = {Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer) and secondary (previous history of breast cancer) groups and compared to patients who never took chemoprevention. Results. 135 (6%) of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%), 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65%) and were diagnosed with equal percentages (44%) of IDC and DCIS. 117 (87%) used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65%) than the nonchemoprevention group (84%/72%). In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients.}, } @article {pmid28074086, year = {2017}, author = {Lu, Y and Zhu, X and Zhang, C and Jiang, K and Huang, C and Qin, X}, title = {Role of CYP2E1 polymorphisms in breast cancer: a systematic review and meta-analysis.}, journal = {Cancer cell international}, volume = {17}, number = {}, pages = {11}, pmid = {28074086}, issn = {1475-2867}, abstract = {BACKGROUND: CYP2E1 polymorphisms have been reported to influence individual's breast cancer susceptibility as a phase I enzyme, but the results of these previous studies remain controversial. We performed a comprehensive meta-analysis to assess their association.

METHODS: A comprehensive search of literature included in various databases (PubMed, Web of Science and Google scholar), published before August 2016, was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the associations between three polymorphisms of CYP2E1 and breast cancer susceptibility. Subgroup analysis, sensitivity analysis and test for publication bias were also performed. A total of 11 separate comparisons involving 4311 cases and 4407 controls were included in the meta-analysis.

RESULTS: Our result showed that there was no significant association between the two common polymorphisms CYP2E1 rs2031920 C>T, CYP2E1*5 Rsa I/Rst I (c1/c2) and BC risk. For CYP2E1*6 Dra I (D/C) polymorphism, a significantly increased BC risk in the overall population was found in genetic model D/C vs. D/D (OR = 1.29, 95% CI = 1.04-1.61, P = 0.023) and C/C + D/C vs. D/D (OR = 1.25, 95% CI = 1.04-1.51, P = 0.019), together with subjects who have at least one C allele (C vs. D: OR = 1.46, 95% CI = 1.20-1.79, P < 0.001). Similar results were also found in subgroup analyses in Caucasians of these three comparison models.

CONCLUSIONS: The present meta-analysis suggests that CYP2E1*6 Dra I (D/C) variation significantly associated with the risk of BC. Individuals with D/C and C/C + D/C genotypes or carried at least one C allele of CYP2E1*6 Dra I (D/C) polymorphism had a significant higher susceptibility to develop BC.}, } @article {pmid28073726, year = {2016}, author = {Gueye, M and Kane Gueye, SM and Ndiaye Gueye, MD and Niasse Dia, F and Gassama, O and Diallo, M and Moreau, JC}, title = {Breast cancer in women younger than 35 years : features and outcomes in the breast unit at Aristide le Dantec Teaching Hospital, Dakar.}, journal = {Medecine et sante tropicales}, volume = {26}, number = {4}, pages = {377-381}, doi = {10.1684/mst.2016.0637}, pmid = {28073726}, issn = {2261-2211}, mesh = {Adult ; Age Factors ; Breast Neoplasms/diagnosis/*epidemiology/therapy ; Female ; Hospitals, Teaching ; Humans ; Retrospective Studies ; Senegal/epidemiology ; Treatment Outcome ; }, abstract = {The aim of this study was to determine the clinical features and outcomes of women younger than 35 years with breast cancer. This study was performed at Gynecologic and Obstetric Clinic of Dakar Teaching Hospital and retrospectively reviewed the records of all women younger than 35 years seen in our department for histologically proven breast cancer. Data were analyzed with SPSS software (Statistical Package for Social Science) Version 23. Between 2007 and 2015, 62 women with breast cancer met the inclusion criteria and were included. The incidence of women in this age group treated in our department was 22.6%. The median age at diagnosis was 29.7 years. The mean time to consultation was 12.5 months, and the disease was locally advanced at diagnosis in 79% of cases. Histological study found 85.5% of cancers were invasive ductal carcinoma. The immunohistochemical study found positive hormone receptors in 12 women (19.4%) and overexpression of HER-2 in 8 (12.9%). Chemotherapy was performed in 54 patients (87.1%), and surgery in 47 (62.9%). Recurrence occurred in 12. In all, 22 women died (35.5%) by the end of the study period. Mean survival was 36.7 months (CI 29.5 to 43.9) and median survival 39.7 months (CI 22.1 to 57.5). This high incidence rate in our study is consistent with that found in young African-American women and is worrisome. These results seem to point towards a genetic origin and call for a thorough search of the profile. They also call also for the involvement of pathologists and collaboration with other research teams.}, } @article {pmid28069161, year = {2017}, author = {Buckley, A and Healy, N and Quinn, A and O'Keeffe, SA}, title = {The value of routine screening mammography in women aged 35-39 years in a symptomatic breast unit.}, journal = {Clinical radiology}, volume = {72}, number = {6}, pages = {517.e7-517.e12}, doi = {10.1016/j.crad.2016.12.007}, pmid = {28069161}, issn = {1365-229X}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging ; *Early Detection of Cancer ; Female ; Humans ; *Mammography ; Retrospective Studies ; }, abstract = {AIM: To determine the breast cancer detection rate at routine bilateral screening mammography in women aged 35-39 years attending a symptomatic breast clinic, in women of population-risk profile with a normal clinical examination.

METHODS AND MATERIALS: A retrospective analysis of all mammograms performed on patients aged 35-39 years at St James's Hospital from 2011-2015 was carried out. Patients with moderate or high familial risk of breast cancer, personal breast cancer history or chest radiation, males, general practitioner (GP) and internal hospital referrals, and those with abnormal clinical examinations were excluded. Included women had "normal", "benign", or undocumented examination findings. Results of imaging, including ultrasound and histopathological results, were recorded. Information was extracted from the hospital's electronic record systems.

RESULTS: Of 4,087 patients aged 35-39 who had bilateral mammograms from 2011-2015, 2,148 patients were excluded from analysis. Of 1,939 included women, four (0.21%) were diagnosed with breast cancer confirmed at histology based on mammographic findings: two invasive ductal carcinoma (8 and 2 mm) and two ductal carcinoma in situ (DCIS; 4.5 mm high-grade DCIS and 2 mm low-grade DCIS). Other histological findings included two B3, 46 B2, and three B1 lesions. Overall, 115 biopsies were performed in this cohort; 55 (47.8%) were attributable to mammographic screening, producing a biopsy rate of 2.8% due to mammography alone.

CONCLUSION: Per 1,000 women screened, 2.1 cases of cancer were detected. This figure would be below accepted international thresholds to undertake screening mammography and raises radiation protection issues. Additionally, a large number of benign biopsies were undertaken, with likely resultant psychological impact. Further studies could inform national guidance.}, } @article {pmid28068979, year = {2017}, author = {Elidrissi Errahhali, M and Elidrissi Errahhali, M and Ouarzane, M and El Harroudi, T and Afqir, S and Bellaoui, M}, title = {First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.}, journal = {BMC women's health}, volume = {17}, number = {1}, pages = {3}, pmid = {28068979}, issn = {1472-6874}, mesh = {Adenocarcinoma, Mucinous/epidemiology/mortality ; Adult ; Breast Neoplasms/*classification/epidemiology/*mortality ; Carcinoma, Ductal/epidemiology/mortality ; Carcinoma, Lobular/epidemiology/mortality ; Carcinoma, Medullary/epidemiology/mortality ; Carcinoma, Papillary/epidemiology/mortality ; Chi-Square Distribution ; Female ; Humans ; Middle Aged ; Molecular Typing/*classification/methods ; Morocco/epidemiology ; *Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women.

METHODS: We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined.

RESULTS: The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis.

CONCLUSIONS: Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.}, } @article {pmid28067867, year = {2017}, author = {Taylor, RA and Fraser, M and Livingstone, J and Espiritu, SM and Thorne, H and Huang, V and Lo, W and Shiah, YJ and Yamaguchi, TN and Sliwinski, A and Horsburgh, S and Meng, A and Heisler, LE and Yu, N and Yousif, F and Papargiris, M and Lawrence, MG and Timms, L and Murphy, DG and Frydenberg, M and Hopkins, JF and Bolton, D and Clouston, D and McPherson, JD and van der Kwast, T and Boutros, PC and Risbridger, GP and Bristow, RG}, title = {Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {13671}, pmid = {28067867}, issn = {2041-1723}, mesh = {Aged ; BRCA2 Protein/deficiency/*genetics ; Carcinoma, Ductal/*genetics/metabolism/pathology/surgery ; DNA Mutational Analysis ; Epigenesis, Genetic ; Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomic Instability ; *Germ-Line Mutation ; Heterozygote ; Humans ; Male ; Mediator Complex/*genetics/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prostate/metabolism/pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*genetics/metabolism/pathology/surgery ; Protein Isoforms/genetics/metabolism ; Retrospective Studies ; Whole Genome Sequencing ; }, abstract = {Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.}, } @article {pmid28067548, year = {2018}, author = {Shenkman, G and Ifrah, K and Shmotkin, D}, title = {The association between negative attitudes toward aging and mental health among middle-aged and older gay and heterosexual men in Israel.}, journal = {Aging & mental health}, volume = {22}, number = {4}, pages = {503-511}, doi = {10.1080/13607863.2016.1274374}, pmid = {28067548}, issn = {1364-6915}, mesh = {Aged ; Aged, 80 and over ; Ageism/*psychology ; Aging/*psychology ; *Attitude ; Depression/*psychology ; *Happiness ; Heterosexuality/*psychology ; Homosexuality, Male/*psychology ; Humans ; Israel ; Male ; Middle Aged ; *Neuroticism ; }, abstract = {OBJECTIVES: The association between negative attitudes toward aging and mental health (indicated by depressive symptoms, neuroticism, and happiness) was explored among Israeli middle-aged and older gay and heterosexual men.

METHOD: In a community-dwelling sample, 152 middle-aged and older gay men and 120 middle-aged and older heterosexual men at the age range of 50-87 (M = 59.3, SD = 7.5) completed measures of negative attitudes toward aging, depressive symptoms, neuroticism, and happiness.

RESULTS: After controlling for socio-demographic characteristics, the association between negative attitudes toward aging and mental health was moderated by sexual orientation, demonstrating that negative attitudes toward aging were more strongly associated with adverse mental health concomitants among middle-aged and older gay men compared to middle-aged and older heterosexual men.

CONCLUSIONS: The findings suggest vulnerability of middle-aged and older gay men to risks of aging, as their mental health is markedly linked with their negative attitudes toward aging. This vulnerability should be addressed by clinicians and counselors who work with middle-aged and older gay men.}, } @article {pmid28062852, year = {2017}, author = {Diaz-Vera, J and Palmer, S and Hernandez-Fernaud, JR and Dornier, E and Mitchell, LE and Macpherson, I and Edwards, J and Zanivan, S and Norman, JC}, title = {A proteomic approach to identify endosomal cargoes controlling cancer invasiveness.}, journal = {Journal of cell science}, volume = {130}, number = {4}, pages = {697-711}, pmid = {28062852}, issn = {1477-9137}, support = {MR/P01058X/1/MRC_/Medical Research Council/United Kingdom ; C596/A12935/CRUK_/Cancer Research UK/United Kingdom ; C596/A18277/CRUK_/Cancer Research UK/United Kingdom ; C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Amino Acids/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Endosomes/*metabolism ; Female ; Gene Knockdown Techniques ; Humans ; Intracellular Membranes/metabolism ; Isotope Labeling ; Models, Biological ; Neoplasm Grading ; Neoplasm Invasiveness ; Neuropilin-2/metabolism ; Protein Binding ; Protein Transport ; Proteomics/*methods ; R-SNARE Proteins/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Estrogen/metabolism ; SNARE Proteins/metabolism ; Survival Analysis ; rab GTP-Binding Proteins/genetics/metabolism ; }, abstract = {We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17- and Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption that accompanies the transition between DCIS and a more invasive phenotype.}, } @article {pmid28051026, year = {2017}, author = {Wang, Y and Liu, M and Jin, ML}, title = {Blood Oxygenation Level-dependent Magnetic Resonance Imaging of Breast Cancer: Correlation with Carbonic Anhydrase IX and Vascular Endothelial Growth Factor.}, journal = {Chinese medical journal}, volume = {130}, number = {1}, pages = {71-76}, pmid = {28051026}, issn = {2542-5641}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*blood/*diagnosis/metabolism ; Carbonic Anhydrase IX/*metabolism ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neovascularization, Pathologic/blood/diagnosis/metabolism ; Oxygen/*blood ; Retrospective Studies ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {BACKGROUND: Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen concentration. The purpose of this study was to investigate whether BOLD-MRI could evaluate hypoxia and angiogenesis of breast invasive ductal carcinoma (IDC).

METHODS: Ninety-eight female patients with IDC were retrospectively included in this research. All patients underwent breast BOLD-MRI at 3.0 T before surgery. R2* values of BOLD-MRI were measured. The expression of carbonic anhydrase IX (CA IX) and vascular endothelial growth factor (VEGF) was analyzed by immunohistochemistry. Spearman's correlation analysis was used to correlate R2* value with CA IX and VEGF levels.

RESULTS: Heterogeneous intensity on BOLD-MRI images was the main finding of IDCs. The mean R2* value was 52.8 ± 18.6 Hz. The R2* values in patients with axillary lymph node metastasis were significantly higher than the R2* values in patients without axillary lymph node metastasis (t = 2.882, P= 0.005). R2* values increased with CA IX level and positively correlated with the level of CA IX (r = 0.616, P< 0.001); however, R2* value had no significantly correlation with the level of VEGF (r = 0.110, P= 0.281).

CONCLUSION: BOLD-MRI could noninvasively evaluate chronic hypoxia of IDC, but not angiogenesis.}, } @article {pmid28050577, year = {2016}, author = {Ding, J and Hu, P and Chen, J and Wu, X and Cao, Y}, title = {The importance of tissue confirmation of metastatic disease in patients with breast cancer: lesson from a brain metastasis case.}, journal = {Oncoscience}, volume = {3}, number = {9-10}, pages = {268-274}, pmid = {28050577}, issn = {2331-4737}, abstract = {BACKGROUND: The discrepancy of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses in breast cancers has been reported. Available systemic therapy for patients with breast cancer is based on the molecular subtypes as identified by IHC and/or FISH. However, these biomarkers may change throughout tumor progression.

CASE PRESENTATION: We report a relatively uncommon case of a 39-year-old Chinese woman with local advanced breast cancer (LABC) treated with 6 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC) regimen neoadjuvant chemotherapy, and subsequently mastectomy, intensity-modulated radiation therapy (IMRT) and tamoxifen followed as regularly. Brain metastatic event appeared in 6 months after mastectomy. Treatment for brain metastasis was surgical resection and followed by whole brain radiotherapy (WBRT) approved by multidisciplinary team (MDT). Initial pathological diagnosis was IDC, cT4N1M0, luminal B (ER+ 90%, PR+90%, HER2 0, Ki67+ 70%) based on ultrasound-guided core needle biopsy. Surgical pathology revealed IDC, pT2N3M0 luminal B (ER+ 20%, PR+20%, HER2 0, Ki67+ 20%). Histological response to neoadjuvant chemotherapy is grade 3 according to the Miller/Payne grading system. Final pathology of brain metastasis showed a HER2 overexpression metastatic breast cancer luminal B (ER+ 70%, PR+ 70%, HER2 2+, Ki67+ 30%), FISH confirmed HER2 overexpression. Weekly paclitaxel plus trastuzumab was given for 12 weeks, then trastuzumab every 3 weeks for a whole year. Patient follow-up is still ongoing, no new events appear yet.

CONCLUSIONS: The determination of hormone receptors and HER2 status should be routinely performed in all involved tissues, if possible, and systemic therapy should be tailored following the latest finding.}, } @article {pmid28041875, year = {2017}, author = {Khan, A and Dellago, H and Terlecki-Zaniewicz, L and Karbiener, M and Weilner, S and Hildner, F and Steininger, V and Gabriel, C and Mück, C and Jansen-Dürr, P and Hacobian, A and Scheideler, M and Grillari-Voglauer, R and Schosserer, M and Grillari, J}, title = {SNEV[hPrp19/hPso4] Regulates Adipogenesis of Human Adipose Stromal Cells.}, journal = {Stem cell reports}, volume = {8}, number = {1}, pages = {21-29}, pmid = {28041875}, issn = {2213-6711}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Adipogenesis/*genetics ; Adipose Tissue/*cytology ; Animals ; Caenorhabditis elegans ; Cell Differentiation/*genetics ; DNA Damage ; DNA Repair Enzymes/*genetics/metabolism ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Insulin/metabolism ; Nuclear Proteins/*genetics/metabolism ; Oxidative Stress ; PPAR gamma/metabolism ; RNA Splicing Factors/*genetics/metabolism ; Stromal Cells/*cytology/*metabolism ; }, abstract = {Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV[hPrp19/hPso4], which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differentiation and led to accumulation of DNA damage in hASCs upon oxidative stress. In addition, we demonstrated that SNEV is required for fat deposition in Caenorhabditis elegans. Consequently, we tested other DDR factors and found that WRN is also required for adipogenesis in both models. These results demonstrate that SNEV regulates adipogenesis in hASCs and indicate that DDR capacity in general might be a pre-requisite for this process.}, } @article {pmid28036342, year = {2016}, author = {Kim, SH and Lee, HS and Kang, BJ and Song, BJ and Kim, HB and Lee, H and Jin, MS and Lee, A}, title = {Dynamic Contrast-Enhanced MRI Perfusion Parameters as Imaging Biomarkers of Angiogenesis.}, journal = {PloS one}, volume = {11}, number = {12}, pages = {e0168632}, pmid = {28036342}, issn = {1932-6203}, mesh = {Adult ; Aged ; Biomarkers/*metabolism ; Carcinoma, Ductal/metabolism/pathology ; Contrast Media/*administration & dosage ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/methods ; Middle Aged ; Neovascularization, Pathologic/*metabolism/*pathology ; Perfusion/methods ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Hypoxia in the tumor microenvironment is the leading factor in angiogenesis. Angiogenesis can be identified by dynamic contrast-enhanced breast MRI (DCE MRI). Here we investigate the relationship between perfusion parameters on DCE MRI and angiogenic and prognostic factors in patients with invasive ductal carcinoma (IDC). Perfusion parameters (Ktrans, kep and ve) of 81 IDC were obtained using histogram analysis. Twenty-fifth, 50th and 75th percentile values were calculated and were analyzed for association with microvessel density (MVD), vascular endothelial growth factor (VEGF) and conventional prognostic factors. Correlation between MVD and ve50 was positive (r = 0.33). Ktrans50 was higher in tumors larger than 2 cm than in tumors smaller than 2 cm. In multivariate analysis, Ktrans50 was affected by tumor size and MVD with 12.8% explanation. There was significant association between Ktrans50 and tumor size and MVD. Therefore we conclude that DCE MRI perfusion parameters are potential imaging biomarkers for prediction of tumor angiogenesis and aggressiveness.}, } @article {pmid28032317, year = {2017}, author = {Kim, GJ and Lee, JY and Choi, HG and Kim, SY and Kim, E and Shim, SH and Nam, JW and Kim, SH and Choi, H}, title = {Cinnamomulactone, a new butyrolactone from the twigs of Cinnamomum cassia and its inhibitory activity of matrix metalloproteinases.}, journal = {Archives of pharmacal research}, volume = {40}, number = {3}, pages = {304-310}, doi = {10.1007/s12272-016-0877-7}, pmid = {28032317}, issn = {1976-3786}, mesh = {4-Butyrolactone/*analogs & derivatives/chemistry/pharmacology ; Arthritis, Rheumatoid/enzymology ; Cell Survival/drug effects ; Cinnamomum/*chemistry ; Dexamethasone/pharmacology ; Fibroblasts/drug effects ; Humans ; Interleukin-1beta/biosynthesis/genetics ; Matrix Metalloproteinase 1/biosynthesis/genetics ; Matrix Metalloproteinase 3/biosynthesis/genetics ; Matrix Metalloproteinase Inhibitors/chemistry/*pharmacology ; Plant Extracts/chemistry/pharmacology ; Plant Stems/chemistry ; Spectrophotometry, Ultraviolet ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {Cinnamomum cassia (Lauraceae) has long been used as one of the most frequently used traditional oriental medicines for the treatment of gastritis, diabetes, blood circulation disturbance and inflammatory diseases. Cinnamomulactone (1), a new butyrolactone was isolated from the twigs of C. cassia together with nine known compounds, coumarin (2), trans-cinnamic acid (3), cinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), 2-methoxycinnamaldehyde (6), 2-hydroxy-cinnamyl alcohol (7), benzoic acid (8), (+)-syringaresinol (9) and phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate (10). The planar structure of 1 was elucidated on the basis of spectroscopic data analysis and its configurations were determined by coupling constant ([3] J HH) analysis and a comparison with specific rotation data of related compounds on the literatures. The structures of known compounds were confirmed by the comparison of their spectroscopic data to the reported values. Compound 10 was isolated for the first time from this plant. Compounds 1, 2, 4, and 9 showed inhibitory activity against matrix metalloproteinases (MMPs) gene expression. Among them, compound 1 has been revealed to suppress the gene expression of MMP-3 and interleukin (IL)-1β as well as MMP-1 in tumor necrosis factor (TNF)-α stimulated rheumatoid arthritis synovial fibroblasts.}, } @article {pmid28031185, year = {2017}, author = {Zhu, L and Ding, Y and Chen, CY and Wang, L and Huo, Z and Kim, S and Sotiriou, C and Oesterreich, S and Tseng, GC}, title = {MetaDCN: meta-analysis framework for differential co-expression network detection with an application in breast cancer.}, journal = {Bioinformatics (Oxford, England)}, volume = {33}, number = {8}, pages = {1121-1129}, pmid = {28031185}, issn = {1367-4811}, support = {R01 CA190766/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Computational Biology/*methods ; Computer Simulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; Receptors, Estrogen/metabolism ; Sample Size ; }, abstract = {MOTIVATION: Gene co-expression network analysis from transcriptomic studies can elucidate gene-gene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results.

RESULTS: In this paper, we propose a meta-analytic framework for detecting differentially co-expressed networks (MetaDCN). Differentially co-expressed seed modules are first detected by optimizing an energy function via simulated annealing. Basic modules sharing common pathways are merged into pathway-centric supermodules and a Cytoscape plug-in (MetaDCNExplorer) is developed to visualize and explore the findings. We applied MetaDCN to two breast cancer applications: ER+/ER- comparison using five training and three testing studies, and ILC/IDC comparison with two training and two testing studies. We identified 20 and 4 supermodules for ER+/ER- and ILC/IDC comparisons, respectively. Ranking atop are 'immune response pathway' and 'complement cascades pathway' for ER comparison, and 'extracellular matrix pathway' for ILC/IDC comparison. Without the need for prior information, the results from MetaDCN confirm existing as well as discover novel disease mechanisms in a systems manner.

R package 'MetaDCN' and Cytoscape App 'MetaDCNExplorer' are available at http://tsenglab.biostat.pitt.edu/software.htm .

CONTACT: ctseng@pitt.edu.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid28030365, year = {2017}, author = {Macho, P}, title = {Individualized Developmental Care in the NICU: A Concept Analysis.}, journal = {Advances in neonatal care : official journal of the National Association of Neonatal Nurses}, volume = {17}, number = {3}, pages = {162-174}, doi = {10.1097/ANC.0000000000000374}, pmid = {28030365}, issn = {1536-0911}, mesh = {Child Development ; *Evidence-Based Medicine ; Family Nursing ; Humans ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Intensive Care, Neonatal/*methods/*standards ; Interprofessional Relations ; Neonatal Nursing/*methods ; Organizational Case Studies ; Parents/education ; Professional-Family Relations ; }, abstract = {BACKGROUND: Individualized developmental care (IDC) is a collection of evidence-based practices that include adapting care practices based on the infant's behavioral and developmental state, involving parents and families in the infant's care, and providing an environment that minimizes over stimulation of the infant.

PURPOSE: To clarify the definition of IDC in the neonatal intensive care unit (NICU) and to provide guidelines for implementation of IDC for healthcare professionals through a concept analysis.

METHOD/SEARCH STRATEGY: A literature review involving a search of multiple electronic databases from January 1982 to November 2016 was performed along with presentation of a model case and attributes of IDC.

CONCLUSIONS: This concept analysis defines and provides guidelines for implementing an individualized developmentally sound environment for infants born premature and their families.

IMPLICATIONS FOR PRACTICE: All NICUs need to strive to provide an environment that supports and promotes IDC. Education needs to be provided to healthcare providers and parents regarding IDC practices.

IMPLICATIONS FOR RESEARCH: Further research into short- and long-term outcomes of IDC is needed. Research into whether IDC is being implemented by NICUs is also needed.}, } @article {pmid28028261, year = {2016}, author = {Jinno, T and Kurumiya, Y and Niwa, T and Sekoguchi, E and Kobayashi, S and Kawai, K and Kiriyama, M}, title = {[Two Cases of ER-Positive Postmenopausal Breast Cancer That Increased in Size during Neoadjuvant Hormone Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {13}, pages = {2539-2542}, pmid = {28028261}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/chemistry/pathology/*therapy ; Carcinoma, Ductal, Breast/chemistry/*therapy ; *Chemoradiotherapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Postmenopause ; Receptors, Estrogen/analysis ; }, abstract = {The first patient was a 62-year-old woman who was referred to our hospital with the complaint of a left breast tumor. She was diagnosed with invasive ductal carcinoma(T1N0M0, stage I). The tumor was ER-positive, PgR-negative, and HER2- negative. She was treated with toremifene, letrozole, and anastrozole as neoadjuvant hormone therapy for 4 months, but the tumor increased in size. The clinical response was judged as progressive disease, and a left partial mastectomy and axillary lymph node dissection were performed. Chemotherapy and radiotherapy were performed after surgery. The second patient was a 68-year-old woman who was referred to our hospital with the complaint of a right breast tumor. She was diagnosed as invasive ductal carcinoma(T1N0M0, stage I). The tumor was ER-positive, PgR-negative, and HER2-negative. She was treated with letrozole as neoadjuvant hormone therapy for 4 months, but the tumor increased in size. The clinical response was judged as progressive disease, and a right partial mastectomy and axillary lymph node dissection were performed. Chemotherapy and radiotherapy were performed after surgery. Although the evidence is still insufficient, with neoadjuvant hormone therapy for hormone-sensitive breast cancer, improved tumor shrinkage and breast conservation have been reported. We experienced two cases in which the tumor increased in size during neoadjuvant hormone therapy; however, even though these cases showed no apparent effect, chemotherapy may be effective in future cases.}, } @article {pmid28027219, year = {2017}, author = {Myckatyn, TM and Wagner, IJ and Mehrara, BJ and Crosby, MA and Park, JE and Qaqish, BF and Moore, DT and Busch, EL and Silva, AK and Kaur, S and Ollila, DW and Lee, CN}, title = {Cancer Risk after Fat Transfer: A Multicenter Case-Cohort Study.}, journal = {Plastic and reconstructive surgery}, volume = {139}, number = {1}, pages = {11-18}, pmid = {28027219}, issn = {1529-4242}, support = {K07 CA154850/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*adverse effects/*methods ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*etiology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Subcutaneous Fat/*transplantation ; }, abstract = {BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers.

METHODS: A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models.

RESULTS: The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8).

CONCLUSION: In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence.

Therapeutic, III.}, } @article {pmid28018301, year = {2016}, author = {Li, J and Sun, L and Xu, F and Qi, H and Shen, C and Jiao, W and Xiao, J and Li, Q and Xu, B and Shen, A}, title = {Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {1961}, pmid = {28018301}, issn = {1664-302X}, abstract = {Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.}, } @article {pmid28009609, year = {2017}, author = {Hickman, RA and Yu, H and Li, J and Kong, M and Shah, RB and Zhou, M and Melamed, J and Deng, FM}, title = {Atypical Intraductal Cribriform Proliferations of the Prostate Exhibit Similar Molecular and Clinicopathologic Characteristics as Intraductal Carcinoma of the Prostate.}, journal = {The American journal of surgical pathology}, volume = {41}, number = {4}, pages = {550-556}, doi = {10.1097/PAS.0000000000000794}, pmid = {28009609}, issn = {1532-0979}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/surgery ; *Cell Proliferation ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/analysis ; Predictive Value of Tests ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/chemistry/*pathology/surgery ; Prostatic Neoplasms/chemistry/*pathology/surgery ; Transcriptional Regulator ERG/analysis ; }, abstract = {Atypical intraductal cribriform proliferations of the prostate (AIP) are loose cribriform proliferations of luminal cells that exhibit greater architectural complexity and/or nuclear atypia than high-grade prostatic intraepithelial neoplasia (HGPIN), but lack the diagnostic criteria for intraductal carcinoma (IDC). The significance of AIP has not been formally established. We compared the clinical, morphologic, and immunohistochemical characteristics of AIP with classic IDC in 310 radical prostatectomy specimens that were received over an 18-month period. Of the 310 cases, 46 cases had AIP only (n=10), IDC only (n=6), or AIP coexisting with IDC (n=30). The ERG status of all 46 AIP/IDC cases was identical to the nearby acinar carcinoma, contrasted to just 3 cases of HGPIN (7%, P<0.01). The degree of uniform phosphatase and tensin homolog (PTEN) loss in 34 selected cases was identical in AIP and IDC (66.7%). No foci of HGPIN showed uniform PTEN loss; there was only 38% concordance of PTEN expression pattern between HGPIN and the nearby acinar carcinoma, unlike AIP and IDC (77% and 81%, respectively, P<0.01). AIP-associated and/or IDC-associated carcinoma (n=46) showed a higher stage and grade compared with acinar-only carcinoma (n=264, P<0.01). AIP-associated carcinoma had similar clinicopathologic features as IDC-associated carcinoma, including preoperative prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis (n=36, P>0.05). In conclusion, AIP shares similar ERG/PTEN immunoprofiles and exhibits similar clinical behavior as IDC, warranting immediate repeat biopsy when AIP is identified on biopsy, as is recommended in the most recent WHO Classification of Tumours of the Urinary System and Male Genital Organs, 2016.}, } @article {pmid28008158, year = {2017}, author = {Chen, QX and Li, JJ and Wang, XX and Lin, PY and Zhang, J and Song, CG and Shao, ZM}, title = {Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.}, journal = {Oncotarget}, volume = {8}, number = {4}, pages = {6206-6215}, pmid = {28008158}, issn = {1949-2553}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Adenoid Cystic/chemistry/mortality/secondary/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Cell Differentiation ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/chemistry/mortality/pathology/*therapy ; United States/epidemiology ; Young Adult ; }, abstract = {Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.}, } @article {pmid28005326, year = {2017}, author = {Chen, Z and Li, X and Wang, J and Tao, L and Long, M and Liang, SJ and Ang, LK and Shu, C and Tsang, HK and Xu, JB}, title = {Synergistic Effects of Plasmonics and Electron Trapping in Graphene Short-Wave Infrared Photodetectors with Ultrahigh Responsivity.}, journal = {ACS nano}, volume = {11}, number = {1}, pages = {430-437}, doi = {10.1021/acsnano.6b06172}, pmid = {28005326}, issn = {1936-086X}, abstract = {Graphene's unique electronic and optical properties have made it an attractive material for developing ultrafast short-wave infrared (SWIR) photodetectors. However, the performance of graphene SWIR photodetectors has been limited by the low optical absorption of graphene as well as the ultrashort lifetime of photoinduced carriers. Here, we present two mechanisms to overcome these two shortages and demonstrate a graphene-based SWIR photodetector with high responsivity and fast photoresponse. In particular, a vertical built-in field is employed in the graphene channel for trapping the photoinduced electrons and leaving holes in graphene, which results in prolonged photoinduced carrier lifetime. On the other hand, plasmonic effects were employed to realize photon trapping and enhance the light absorption of graphene. Thanks to the above two mechanisms, the responsivity of this proposed SWIR photodetector is up to a record of 83 A/W at a wavelength of 1.55 μm with a fast rising time of less than 600 ns. This device design concept addresses key challenges for high-performance graphene SWIR photodetectors and is promising for the development of mid/far-infrared optoelectronic applications.}, } @article {pmid27996889, year = {2017}, author = {Alduk, AM and Brcic, I and Podolski, P and Prutki, M}, title = {Correlation of MRI features and pathohistological prognostic factors in invasive ductal breast carcinoma.}, journal = {Acta clinica Belgica}, volume = {72}, number = {5}, pages = {306-312}, doi = {10.1080/17843286.2016.1266432}, pmid = {27996889}, issn = {2295-3337}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: The aim of this study was to correlate magnetic resonance imaging (MRI) features of invasive ductal carcinomas (IDC) with pathohistological prognostic factors. Such an association, if present, could have significant translational implications for early identification of aggressive types of breast cancer.

MATERIALS AND METHODS: One hundred and fourteen consecutive women with IDC who underwent breast MRI within one month prior to surgery were included in this retrospective study. MRI features were analyzed and then interpreted with a Göttingen score (GS) that included morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve). Histological specimens were analyzed for tumor size, axillary lymph node status, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2, and Ki-67.

RESULTS: By multivariate analysis, a smooth margin was a significant, independent predictor of a larger tumor size (p = 0.041), lymph node invasion (p = 0.013), and lower expression of ER (p = 0.022). High GS was a significant, independent predictor of a higher histological grade (p = 0.022) while round or oval shape of lesion was independent predictor of a higher PR expression (p = 0.027).

CONCLUSION: A smooth margin of breast cancer on breast MRI was able to predict positive axillary lymph nodes, larger tumor size, and lower expression of ER. Except for a higher histological grade, GS was not able to predict other unfavorable prognostic factors, probably due to the fact that smooth margins were assigned fewer points than spiculated margins.}, } @article {pmid27994939, year = {2016}, author = {Spagnolo, DM and Gyanchandani, R and Al-Kofahi, Y and Stern, AM and Lezon, TR and Gough, A and Meyer, DE and Ginty, F and Sarachan, B and Fine, J and Lee, AV and Taylor, DL and Chennubhotla, SC}, title = {Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers.}, journal = {Journal of pathology informatics}, volume = {7}, number = {}, pages = {47}, pmid = {27994939}, issn = {2229-5089}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; T32 EB009403/EB/NIBIB NIH HHS/United States ; U01 CA204826/CA/NCI NIH HHS/United States ; U54 HG008540/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME) are key contributors to heterogeneity.

METHODS: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI) and visually represent heterogeneity with a two-dimensional map.

RESULTS: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score.

CONCLUSIONS: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI), which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different components within the TME. We hypothesize that PMI will uncover key spatial interactions in the TME that contribute to disease proliferation and progression.}, } @article {pmid27992016, year = {2016}, author = {Eugênio, DS and Souza, JA and Chojniak, R and Bitencourt, AG and Graziano, L and Souza, EF}, title = {Breast cancer features in women under the age of 40 years.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {62}, number = {8}, pages = {755-761}, doi = {10.1590/1806-9282.62.08.755}, pmid = {27992016}, issn = {1806-9282}, mesh = {Adult ; Biopsy ; Brazil ; Breast Neoplasms/*diagnostic imaging/*pathology ; Family Health ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Mass Screening ; Neoplasm Grading ; Neoplasm Staging ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE:: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years.

METHOD:: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120) patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI). The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients.

RESULTS:: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0%) had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92) patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122) primary tumors were diagnosed, of which 112 were invasive (95%). The most common histological type was invasive ductal carcinoma (73.8%). Luminal B was the predominant molecular subtype (42.6%). Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%). At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common.

CONCLUSION:: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.}, } @article {pmid27990252, year = {2016}, author = {Ashano, E and Isewon, I and Oyelade, J and Adebiyi, E}, title = {Cluster analysis of Plasmodium RNA-seq time-course data identifies stage-specific co-regulated biological processes and regulatory elements.}, journal = {F1000Research}, volume = {5}, number = {}, pages = {}, pmid = {27990252}, issn = {2046-1402}, abstract = {In this study, we interpreted RNA-seq time-course data of three developmental stages of Plasmodium species by clustering genes based on similarities in their expression profile without prior knowledge of the gene function. Functional enrichment of clusters of upregulated genes at specific time-points reveals potential targetable biological processes with information on their timings. We identified common consensus sequences that these clusters shared as potential points of coordinated transcriptional control. Five cluster groups showed upregulated profile patterns of biological interest. This included two clusters from the Intraerythrocytic Developmental Cycle (cluster 4 = 16 genes, and cluster 9 = 32 genes), one from the sexual development stage (cluster 2 = 851 genes), and two from the gamete-fertilization stage in the mosquito host (cluster 4 = 153 genes, and cluster 9 = 258 genes). The IDC expressed the least numbers of genes with only 1448 genes showing any significant activity of the 5020 genes (~29%) in the experiment. Gene ontology (GO) enrichment analysis of these clusters revealed a total of 671 uncharacterized genes implicated in 14 biological processes and components associated with these stages, some of which are currently being investigated as drug targets in on-going research. Five putative transcription regulatory binding motifs shared by members of each cluster were also identified, one of which was also identified in a previous study by separate researchers. Our study shows stage-specific genes and biological processes that may be important in antimalarial drug research efforts. In addition, timed-coordinated control of separate processes may explain the paucity of factors in parasites.}, } @article {pmid27988039, year = {2017}, author = {Bobbo, M and Pinamonti, B and Merlo, M and Stolfo, D and Iorio, A and Ramani, F and Barbati, G and Carriere, C and Massa, L and Poli, S and Scapol, S and Gigli, M and Di Lenarda, A and Sinagra, G}, title = {Comparison of Patient Characteristics and Course of Hypertensive Hypokinetic Cardiomyopathy Versus Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {119}, number = {3}, pages = {483-489}, doi = {10.1016/j.amjcard.2016.10.014}, pmid = {27988039}, issn = {1879-1913}, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Amiodarone/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Anti-Arrhythmia Agents/therapeutic use ; Cardiomyopathies/etiology/physiopathology/therapy ; Cardiomyopathy, Dilated/*physiopathology/therapy ; Cause of Death ; Disease Progression ; Female ; Heart Failure/etiology/*physiopathology/therapy ; Heart Transplantation ; Heart-Assist Devices ; Humans ; Hypertension/complications ; Hypertrophy, Left Ventricular/etiology/*physiopathology/therapy ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Mortality ; Retrospective Studies ; Stroke Volume ; Tachycardia, Ventricular/epidemiology ; Ventricular Dysfunction, Left/etiology/*physiopathology/therapy ; Ventricular Fibrillation/epidemiology ; Ventricular Remodeling ; }, abstract = {Hypertensive hypokinetic cardiomyopathy (HHC) is defined by left ventricular (LV) systolic dysfunction with a history of systemic hypertension as the only possible cause. Although commonly encountered in clinical practice, its characterization and differences with true idiopathic dilated cardiomyopathy (IDC) are lacking. The aim of this study was to characterize the clinical instrumental features and the natural history of HHC. We analyzed the data of 4,191 patients referred to our center for newly diagnosed LV systolic dysfunction from 2005 to 2010. Of them, 310 presented idiopathic LV systolic dysfunction (LV ejection fraction <50%): 136 (44%) had a history of systemic hypertension and were defined HHC. The remaining 174 patients were considered IDC. Compared with patients with IDC, those with HHC were older (63 ± 11 vs 47 ± 14 years, p <0.001), with worse comorbidity profile, higher blood pressure, and increased LV mass. During follow-up, patients with HHC showed earlier and higher proportion of LV reverse remodeling (46% vs 21% at 6 months' follow-up). Moreover, they had a better long-term survival free from cardiovascular death/ventricular assist device/heart transplant/malignant ventricular arrhythmias (5.1 vs 12.6 in HHC and IDC, p = 0.03). Indeed, their mortality was mainly driven by noncardiovascular causes (at 10 years 9.6% vs 1.7% in HHC and IDC, p <0.001). In conclusion, HHC has a high prevalence among patients with "idiopathic" LV dysfunction. The natural history of patients with HHC is characterized by a rapid response to optimal therapy for heart failure, a favorable cardiovascular outcome, and a relevant incidence of noncardiovascular events.}, } @article {pmid27979331, year = {2017}, author = {Loft, A and Forss, I and Mandrup, S}, title = {Genome-Wide Insights into the Development and Function of Thermogenic Adipocytes.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {28}, number = {2}, pages = {104-120}, doi = {10.1016/j.tem.2016.11.005}, pmid = {27979331}, issn = {1879-3061}, mesh = {Adipocytes/*metabolism ; Adipogenesis/genetics/*physiology ; Adipose Tissue, Brown/metabolism ; Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Thermogenesis/genetics/*physiology ; }, abstract = {Brown and brown-like adipocytes are specialized adipocytes with a high capacity to convert metabolic energy to heat. This function is not only eminent in supporting organismal thermogenesis, but may also have potential in the fight against obesity. The latter has spurred a massive interest in understanding the development and regulation of these thermogenic adipocytes. Here, we review how genome-wide studies based on next-generation sequencing have provided insight into how the chromatin and transcriptional landscapes are established in thermogenic adipocytes and how thermogenic signals can change the genomic programming of white adipocytes. Furthermore, we discuss how the integration of genomic data can be used to discover novel transcriptional pathways that may be modulated as part of therapeutic strategies for the treatment of obesity.}, } @article {pmid27965971, year = {2016}, author = {Galasso, M and Costantino, G and Pasquali, L and Minotti, L and Baldassari, F and Corrà, F and Agnoletto, C and Volinia, S}, title = {Profiling of the Predicted Circular RNAs in Ductal In Situ and Invasive Breast Cancer: A Pilot Study.}, journal = {International journal of genomics}, volume = {2016}, number = {}, pages = {4503840}, pmid = {27965971}, issn = {2314-436X}, abstract = {The recent advantage obtained by next generation sequencing allows a depth investigation of a new "old" kind of noncoding transcript, the circular RNAs. Circular RNAs are nontranslated RNAs, typically nonpolyadenylated, with a resistance to exonucleases that gives them the ability to be more stable than the common linear RNA isoforms. We used a bioinformatic detection tool (CIRCexplorer) to research predictive circRNAs from the next generation sequenced data of five samples of ductal in situ carcinoma (DCIS) and matched adjacent invasive ductal carcinoma (IDC). Furthermore, we also investigated the circular RNAs expressed in MCF7, an invasive breast ductal carcinoma cell line. We described the genomic context of the predicted circular RNAs and we address the hypothetical possible functional roles. This study showed a perspective of a panel of predictive circRNAs identified and the function that circRNAs could exert.}, } @article {pmid27956549, year = {2017}, author = {Morgenstern, J and Fleming, T and Schumacher, D and Eckstein, V and Freichel, M and Herzig, S and Nawroth, P}, title = {Loss of Glyoxalase 1 Induces Compensatory Mechanism to Achieve Dicarbonyl Detoxification in Mammalian Schwann Cells.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {8}, pages = {3224-3238}, pmid = {27956549}, issn = {1083-351X}, mesh = {Aldehyde Reductase/*metabolism ; Animals ; Cells, Cultured ; Gene Deletion ; Gene Knockout Techniques ; Glycation End Products, Advanced/*metabolism ; Lactoylglutathione Lyase/genetics/*metabolism ; Mice ; Oxidative Stress ; Pyruvaldehyde/*metabolism ; Schwann Cells/cytology/*metabolism ; }, abstract = {The glyoxalase system is a highly specific enzyme system existing in all mammalian cells that is responsible for the detoxification of dicarbonyl species, primarily methylglyoxal (MG). It has been implicated to play an essential role in preventing the increased formation of advanced glycation end products under certain pathological conditions. We have established the first glyoxalase 1 knock-out model (GLO1[-/-]) in mammalian Schwann cells using the CRISPR/Cas9 technique to investigate compensatory mechanisms. Neither elevated concentrations of MG nor associated protein modifications were observed in GLO1[-/-] cells. Alternative detoxification of MG in GLO1[-/-] is achieved by increased catalytic efficiency of aldose reductase toward hemithioacetal (product of glutathione and MG), which is most likely caused by S-nitrosylation of aldose reductase. The hemithioacetal is mainly converted into lactaldehyde, which is paralleled by a loss of reduced glutathione. Inhibition of aldose reductase in GLO1[-/-] cells is associated with an increased sensitivity against MG, elevated intracellular MG levels, associated modifications, as well as increased oxidative stress. Our data suggest that aldose reductase can compensate for the loss of GLO1. This might be of clinical importance within the context of neuronal diseases caused by an impaired glyoxalase system and elevated levels of dicarbonyl species, such as MG.}, } @article {pmid27932057, year = {2017}, author = {Brings, S and Fleming, T and De Buhr, S and Beijer, B and Lindner, T and Wischnjow, A and Kender, Z and Peters, V and Kopf, S and Haberkorn, U and Mier, W and Nawroth, PP}, title = {A scavenger peptide prevents methylglyoxal induced pain in mice.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1863}, number = {3}, pages = {654-662}, doi = {10.1016/j.bbadis.2016.12.001}, pmid = {27932057}, issn = {0925-4439}, mesh = {Amino Acid Sequence ; Analgesics/blood/chemistry/pharmacokinetics/*therapeutic use ; Animals ; Mice ; Mice, Inbred C57BL ; Pain/blood/metabolism/*prevention & control ; Peptides, Cyclic/blood/chemistry/pharmacokinetics/*therapeutic use ; Pyruvaldehyde/blood/*metabolism ; Serum Albumin/metabolism ; }, abstract = {The reactive metabolite methylglyoxal (MG) has been identified as mediator of pain. Scavenging of free MG and the prevention of MG-derived post-translational modifications may provide a useful therapeutic treatment. An arginine-rich, fatty acid coupled, cyclic peptide (CycK(Myr)R4E) with high proteolytic stability and prolonged circulation was developed for the scavenging of MG. It was shown to reduce the formation of albumin-MG adducts in vitro and prevented MG-induced pain by reducing plasma MG levels through the formation of peptide-MG adducts in vivo. CycK(Myr)R4E therefore presents a promising option for the treatment of pain and other diabetic complications associated with high MG levels.}, } @article {pmid27928699, year = {2017}, author = {Eaton, AA and Pesce, CE and Murphy, JO and Stempel, MM and Patil, SM and Brogi, E and Hudis, CA and El-Tamer, M}, title = {Estimating the OncotypeDX score: validation of an inexpensive estimation tool.}, journal = {Breast cancer research and treatment}, volume = {161}, number = {3}, pages = {435-441}, pmid = {27928699}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Female ; Gene Expression Profiling/*methods/standards ; Genetic Testing/*methods/standards ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Reproducibility of Results ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score.

METHODS: Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs.

RESULTS: Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score <18, 18-30, >30). 41% of patients were predicted to have OncotypeDX score <18, of these 83, 16, and 2% had true scores of <18, 18-30, and >30, respectively.

CONCLUSIONS: Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).}, } @article {pmid27924953, year = {2016}, author = {Wang, Z and Samaraweera, RL and Reichl, C and Wegscheider, W and Mani, RG}, title = {Tunable electron heating induced giant magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {38516}, pmid = {27924953}, issn = {2045-2322}, abstract = {Electron-heating induced by a tunable, supplementary dc-current (Idc) helps to vary the observed magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system. The magnetoresistance at B = 0.3 T is shown to progressively change from positive to negative with increasing Idc, yielding negative giant-magnetoresistance at the lowest temperature and highest Idc. A two-term Drude model successfully fits the data at all Idc and T. The results indicate that carrier heating modifies a conductivity correction σ1, which undergoes sign reversal from positive to negative with increasing Idc, and this is responsible for the observed crossover from positive- to negative- magnetoresistance, respectively, at the highest B.}, } @article {pmid27924790, year = {2017}, author = {Li, BK and Chen, BS and Xin, YH and Liu, CX and Zheng, SB and Xu, YW and Li, HL and Zou, Y and Li, LP}, title = {Can the lower urinary tract storage symptoms be completely resolved after plasmakinetic enucleation of the prostate?.}, journal = {Asian journal of andrology}, volume = {19}, number = {6}, pages = {655-658}, pmid = {27924790}, issn = {1745-7262}, mesh = {Aged ; Humans ; Lower Urinary Tract Symptoms/etiology/physiopathology/*surgery ; Male ; Middle Aged ; Prostate/physiopathology/*surgery ; Prostatic Hyperplasia/complications/physiopathology/*surgery ; Quality of Life ; Transurethral Resection of Prostate/*methods ; Treatment Outcome ; Urodynamics/physiology ; }, abstract = {The aim of this study was to determine whether the lower urinary tract storage symptoms of benign prostatic obstruction (BPO) could be completely resolved after plasmakinetic enucleation of the prostate (PKEP) and the possible predictors of persistent symptoms. Two hundred and sixty-seven cases of BPO performed PKEP from July 2008 to June 2009 were retrospectively analyzed. Five-year postoperative data were collected and compared with the preoperative data. According to the urodynamic results, the patients were divided into involuntary detrusor contraction (IDC) group (n = 95) and no IDC group (n = 172) preoperatively; the patients with IDC were divided into IDC-persistent group (n = 33) and IDC-resolved group (n = 62) after PKEP. The predictors of persistent IDC were analyzed. Compared with the preoperative data, the 5-year postoperative data showed that the IDC rate was lower (P = 0.000), Overactive Bladder Symptom Score (OABSS) was lower (P = 0.000), maximum cystometric capacity (MCC) was larger (P = 0.000), Prostate volume (PV) was smaller (P = 0.000), and prostate-specific antigen (PSA) was lower (P = 0.000). Compared with the no IDC group, the IDC group showed that the age was older (P = 0.016), MCC was smaller (P = 0.004), PSA was higher (P = 0.016), and Chronic Inflammation rate was higher (P = 0.004). Compared with IDC-resolved group after PKEP, IDC-persistent group showed that the age was older (P = 0.019), MCC was smaller (P = 0.000), PSA was higher (P = 0.013), and Chronic Inflammation rate was higher (P = 0.032). The present study shows that the storage symptoms are still needed to be focused on after PKEP. The advanced patient age, MCC, PSA, and chronic inflammation may be the important clinical predictors of persistent IDC.}, } @article {pmid27923458, year = {2016}, author = {Scheideler, M}, title = {MicroRNAs in adipocyte formation and obesity.}, journal = {Best practice & research. Clinical endocrinology & metabolism}, volume = {30}, number = {5}, pages = {653-664}, doi = {10.1016/j.beem.2016.11.009}, pmid = {27923458}, issn = {1878-1594}, mesh = {Adipocytes, Brown/cytology/*metabolism ; Animals ; Energy Metabolism ; Humans ; MicroRNAs/*genetics/metabolism ; Obesity/*genetics/metabolism ; }, abstract = {The worldwide epidemic of obesity demands novel and more effective therapeutic approaches. Fat cells are at the core of energy metabolism trying either to cope with a positive energy balance by hypertrophy and hyperplasia of energy storing white adipocytes or to counteract obesity by the induction of non-shivering thermogenesis in energy combusting brite/brown adipocytes. However, the comprehensive regulatory network of adipocyte formation remains to be elucidated. MicroRNAs are an emerging class of important regulatory determinants in many biological processes and diseases, including adipocyte formation and obesity. In this review, microRNAs governing the formation of white, brite and brown adipocytes as well as candidates with impact on obesity are overviewed, concluded with recommendations for further research that considers prerequisites for successful therapeutic applications.}, } @article {pmid27923361, year = {2016}, author = {Balekouzou, A and Yin, P and Pamatika, CM and Bishwajit, G and Nambei, SW and Djeintote, M and Ouansaba, BE and Shu, C and Yin, M and Fu, Z and Qing, T and Yan, M and Chen, Y and Li, H and Xu, Z and Koffi, B}, title = {Epidemiology of breast cancer: retrospective study in the Central African Republic.}, journal = {BMC public health}, volume = {16}, number = {1}, pages = {1230}, pmid = {27923361}, issn = {1471-2458}, mesh = {Adult ; Breast Neoplasms/*epidemiology/pathology ; Central African Republic/epidemiology ; Female ; Humans ; Incidence ; Lymph Nodes/pathology ; Middle Aged ; Prevalence ; Retrospective Studies ; Urban Population/statistics & numerical data ; }, abstract = {BACKGROUND: Breast cancer is recognised as a major public health problem in developing countries; however, there is very limited evidence about its epidemiology in the Central African Republic. The aim of this study was to investigate the epidemiological and histopathological characteristics of breast cancer in Bangui.

METHODS: This is a retrospective study based on the data collected from pathological anatomy records from 2003 to 2015 in Bangui. A questionnaire was designed to collect information and data was analysed using descriptive and inferential statistical methods.

RESULTS: The mean age was 45.83 (SD = 13.5) years. The age group of 45-54 years represented the majority of the study population (29.3%). Over 69.5% of the women were housewives with a moderate economic status (56.9%). Less than 14% of the study population had a level of academic degree and 85.6% lived in cities. The breast cancer prevalence was 15.27%. The age-standardized incidence and death by world population (ASW) were 11.19/100,000 and 9.97/100,000 respectively. 50-54 years were most affected. Left breast cancer is mainly common and the time between first symptoms and consultation is more than 48 months. Most (69%) of the samples analysed were lumpectomy. The most common morphology of breast cancer was invasive ductal carcinoma (64.9%). Scarff Bloom Richardson III was the main grade in both common pathological types, but their proportion showed no significant increase along with time (χ2 = 7.06, p = 0.54). Invasion of regional lymph node differed significantly among the pathological type of breast cancer (χ2 = 24.6, p = 0.02). Surgery and chemotherapy were appropriate treatment yet 84.5% of the cases died.

CONCLUSION: The findings of this study showed that breast cancer is common and mostly affected women. Epidemiological trends are more or less common to those of developing countries with a predominance of invasive ductal carcinoma. However, most of the women studied live in an urban area and developed the disease in advanced stage. The establishment of an appropriate framework will effectively contribute to promoting the early detection and reducing the incidence of this disease in the population.}, } @article {pmid27917007, year = {2016}, author = {Murakami, E and Nakanishi, Y and Hirotani, Y and Ohni, S and Tang, X and Masuda, S and Enomoto, K and Sakurai, K and Amano, S and Yamada, T and Nemoto, N}, title = {Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.}, journal = {Acta histochemica et cytochemica}, volume = {49}, number = {5}, pages = {131-140}, pmid = {27917007}, issn = {0044-5991}, abstract = {Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.}, } @article {pmid27916938, year = {2016}, author = {Pehserl, AM and Ress, AL and Stanzer, S and Resel, M and Karbiener, M and Stadelmeyer, E and Stiegelbauer, V and Gerger, A and Mayr, C and Scheideler, M and Hutterer, GC and Bauernhofer, T and Kiesslich, T and Pichler, M}, title = {Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {17}, number = {12}, pages = {}, pmid = {27916938}, issn = {1422-0067}, mesh = {Animals ; Caco-2 Cells ; Cell Cycle Checkpoints/drug effects ; Colorectal Neoplasms/*drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*biosynthesis/genetics ; Mutation ; Niacinamide/administration & dosage/*analogs & derivatives ; Phenylurea Compounds/*administration & dosage ; Proto-Oncogene Proteins p21(ras)/genetics ; Sorafenib ; }, abstract = {MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.}, } @article {pmid27916594, year = {2017}, author = {Chen, SQ and Huang, M and Shen, YY and Liu, CL and Xu, CX}, title = {Application of Abbreviated Protocol of Magnetic Resonance Imaging for Breast Cancer Screening in Dense Breast Tissue.}, journal = {Academic radiology}, volume = {24}, number = {3}, pages = {316-320}, doi = {10.1016/j.acra.2016.10.003}, pmid = {27916594}, issn = {1878-4046}, mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Density/*physiology ; Breast Neoplasms/*diagnostic imaging ; Early Detection of Cancer/methods ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {RATIONALE AND OBJECTIVES: The study aimed to evaluate the usefulness of an abbreviated protocol (AP) of magnetic resonance imaging (MRI) in comparison to a full diagnostic protocol (FDP) of MRI in the breast cancer screening with dense breast tissue.

MATERIALS AND METHODS: There are 478 female participants with dense breast tissue and negative mammography results, who were imaged with MRI using AP and FDP. The AP and FDP images were analyzed separately, and the sensitivity and specificity of breast cancer detection were calculated. The chi-square test and receiver operating characteristics curves were used to assess the breast cancer diagnostic capabilities of the two protocols.

RESULTS: Sixteen cases of breast cancer from 478 patients with dense breasts were detected using the FDP method, with pathologic confirmation of nine cases of ductal carcinoma in situ, six cases of invasive ductal carcinoma, and one case of mucinous carcinoma. Fifteen cases of breast cancer were successfully screened using the AP method. The sensitivity showed no obvious significant difference between AP and FDP (χ[2] = 0.592, P = 0.623), but the specificity showed a statistically significant difference (χ[2] = 4.619, P = 0.036). The receiver operating characteristics curves showed high efficacy of both methods in the detection of breast cancer in dense breast tissue (the areas under the curve were 0.931 ± 0.025 and 0.947 ± 0.024, respectively), and the ability to diagnose breast cancer was not statistically significantly different between the two methods.

CONCLUSIONS: The AP of MRI may improve the detection rate of breast cancer in dense breast tissue, and it may be useful in efficient breast cancer screening.}, } @article {pmid27909910, year = {2016}, author = {Berriel Diaz, M and Herzig, S and Schafmeier, T}, title = {Biological Mechanisms for the Effect of Obesity on Cancer Risk: Experimental Evidence.}, journal = {Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer}, volume = {208}, number = {}, pages = {219-242}, doi = {10.1007/978-3-319-42542-9_12}, pmid = {27909910}, issn = {0080-0015}, mesh = {Adipokines/*metabolism ; Adipose Tissue/*metabolism/physiopathology ; Adiposity ; Animals ; Biomarkers, Tumor/*metabolism ; Cell Transformation, Neoplastic/*metabolism/pathology ; Energy Metabolism ; Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/metabolism ; Neoplasms/*etiology/metabolism/pathology ; Obesity/*complications/metabolism/physiopathology ; Risk Factors ; Signal Transduction ; }, abstract = {Multiple epidemiological studies demonstrated that overweight and obesity significantly increase the risk of several types of cancer. As the prevalence of obesity is dramatically rising, it is expected that it will represent one of the major lifestyle-associated risk factors for cancer development in the near future. Numerous recent studies expanded knowledge about key players and pathways, which are deregulated in the obese state and potentially promote cancer initiation, progression and aggressiveness via remote and local effects. These players include (but are not limited to) insulin/IGF, adipokines and inflammatory signaling molecules as well as metabolites. Nevertheless, the detailed mechanisms linking obesity and malignant transformation at the systemic, cellular and molecular level still demand further investigation. Additionally, dysfunctional molecular metabolic pathways appear to be specific for distinct cancer entities, thereby yet precluding definition of a common principle. This chapter will present an overview of the current knowledge of molecular nodes linking obesity and cancer and will briefly touch upon potential therapy options addressing metabolic cancer etiologies.}, } @article {pmid27904452, year = {2016}, author = {Petric, P and Hudej, R and Al-Hammadi, N and Segedin, B}, title = {Virtual modelling of novel applicator prototypes for cervical cancer brachytherapy.}, journal = {Radiology and oncology}, volume = {50}, number = {4}, pages = {433-441}, pmid = {27904452}, issn = {1318-2099}, abstract = {BACKGROUND: Standard applicators for cervical cancer Brachytherapy (BT) do not always achieve acceptable balance between target volume and normal tissue irradiation. We aimed to develop an innovative method of Target-volume Density Mapping (TDM) for modelling of novel applicator prototypes with optimal coverage characteristics. Patients and methods. Development of Contour-Analysis Tool 2 (CAT-2) software for TDM generation was the core priority of our task group. Main requests regarding software functionalities were formulated and guided the coding process. Software validation and accuracy check was performed using phantom objects. Concepts and terms for standardized workflow of TDM post-processing and applicator development were introduced.

RESULTS: CAT-2 enables applicator-based co-registration of Digital Imaging and Communications in Medicine (DICOM) structures from a sample of cases, generating a TDM with pooled contours in applicator-eye-view. Each TDM voxel is assigned a value, corresponding to the number of target contours encompassing that voxel. Values are converted to grey levels and transformed to DICOM image, which is transported to the treatment planning system. Iso-density contours (IDC) are generated as lines, connecting voxels with same grey levels. Residual Volume at Risk (RVR) is created for each IDC as potential volume that could contain organs at risk. Finally, standard and prototype applicators are applied on the TDM and virtual dose planning is performed. Dose volume histogram (DVH) parameters are recorded for individual IDC and RVR delineations and characteristic curves generated. Optimal applicator configuration is determined in an iterative manner based on comparison of characteristic curves, virtual implant complexities and isodose distributions.

CONCLUSIONS: Using the TDM approach, virtual applicator prototypes capable of conformal coverage of any target volume, can be modelled. Further systematic assessment, including studies on clinical feasibility, safety and effectiveness are needed before routine use of novel prototypes can be considered.}, } @article {pmid27903846, year = {2017}, author = {Autenshlyus, AI and Arkhipov, SA and Kunts, TA and Marinkin, IO and Mikhailova, ES and Karpukhina, XV and Varaksin, NA}, title = {Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors.}, journal = {International journal of immunopathology and pharmacology}, volume = {30}, number = {1}, pages = {83-88}, pmid = {27903846}, issn = {2058-7384}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cytokines/*metabolism ; Female ; Fibroadenoma/*metabolism ; Humans ; Middle Aged ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = -0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = -0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.}, } @article {pmid27903648, year = {2017}, author = {Pfaff, DH and Fleming, T and Nawroth, P and Teleman, AA}, title = {Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification.}, journal = {The Journal of biological chemistry}, volume = {292}, number = {2}, pages = {685-690}, pmid = {27903648}, issn = {1083-351X}, support = {P40 OD018537/OD/NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Survival ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Nerve Tissue Proteins/genetics/*metabolism ; Protein Deglycase DJ-1 ; Pyruvaldehyde/*pharmacokinetics/*toxicity ; }, abstract = {Methylglyoxal (MG) is a reactive metabolite that forms adducts on cysteine, lysine and arginine residues of proteins, thereby affecting their function. Methylglyoxal is detoxified by the Glyoxalase system, consisting of two enzymes, Glo1 and Glo2, that act sequentially to convert MG into d-lactate. Recently, the Parkinsonism-associated protein DJ-1 was described in vitro to have glyoxalase activity, thereby detoxifying the MG metabolite, or deglycase activity, thereby removing the adduct formed by MG on proteins. Since Drosophila is an established model system to study signaling, neurodegeneration, and metabolic regulation in vivo, we asked whether DJ-1 contributes to MG detoxification in vivo Using both DJ-1 knockdown in Drosophila cells in culture, and DJ-1β knock-out flies, we could detect no contribution of DJ-1 to survival to MG challenge or to accumulation of MG protein adducts. Furthermore, we provide data suggesting that the previously reported deglycation activity of DJ-1 can be ascribed to a TRIS buffer artifact.}, } @article {pmid27900579, year = {2017}, author = {Saito, R and Miki, Y and Hata, S and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Aryl hydrocarbon receptor induced intratumoral aromatase in breast cancer.}, journal = {Breast cancer research and treatment}, volume = {161}, number = {3}, pages = {399-407}, doi = {10.1007/s10549-016-4063-x}, pmid = {27900579}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aromatase/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Estrogens/biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ligands ; MCF-7 Cells ; Middle Aged ; Receptors, Aryl Hydrocarbon/*metabolism ; }, abstract = {PURPOSE: Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells.

METHODS: We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231.

RESULTS: AhR stimulation induced the mRNA expression of the aromatase gene in vitro in three breast carcinoma cell lines, and increased estrogen synthesis in MCF-7 cell line. Results of microarray analysis showed that AhR-induced aromatase expression was associated with BRCA1 induction. Analysis of patients with breast cancer showed a significant positive correlation between intratumoral AhR and aromatase status. We also compared the effects of AhR stimulation on the induction of intratumoral estrogen synthesis and inhibition of the ER signaling pathway, because AhR exerts contradictory effects on estrogen action in breast carcinoma cells. AhR-induced aromatase expression persisted for a significantly longer duration than AhR-induced ER pathway inhibition. Moreover, breast carcinoma cells treated with an AhR agonist tended to show earlier cell proliferation after removing the agonist than cells not treated with the AhR agonist.

CONCLUSION: The results of the present study suggest that AhR stimulates estrogen-dependent progression of breast carcinoma by inducing aromatase expression under some conditions. These results provide new insights on the possible roles of environmental toxins in breast cancer development.}, } @article {pmid27899970, year = {2016}, author = {Petroni, S and Caldarola, L and Scamarcio, R and Giotta, F and Latorre, A and Mangia, A and Simone, G}, title = {FISH testing of HER2 immunohistochemistry 1+ invasive breast cancer with unfavorable characteristics.}, journal = {Oncology letters}, volume = {12}, number = {5}, pages = {3115-3122}, pmid = {27899970}, issn = {1792-1074}, abstract = {Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+. Of these 102 women with IBC who underwent surgery, 75 entered the study (73.5%). A total of 48 out of 75 (64%) IBC samples (patients' median age, 60.75 years) were selected according to ≥1 unfavorable tumor characteristics, and tested by fluorescence in situ hybridization (FISH). Of these 48 IBC samples scoring 1+ by IHC, 22 (46%) exhibited high histological grade (G3), 23 (48%) had a high proliferative index (Ki-67, >30%), 27 (56%) showed vascular invasion and 32 out of 41 evaluable cases (78%) were node-positive. Regarding hormone receptor expression, 3 (6%) and 10 (21%) cases were negative for estrogen and progesterone receptors expression, respectively. FISH was performed on 48 IBC cases scoring 1+ by IHC, and 7 infiltrating ductal carcinomas (IDCs) (14.6%) demonstrated HER2 amplification with a high proliferative index. In 42 IDC samples, statistical analysis evidenced a significant association between histological grade and high proliferative index (P=0.0200). In addition, in 48 HER2 scoring 1+ IBCs, Fisher's exact test evidenced a significant association between the presence of gene amplification and high proliferative index (P=0.0033). Based on these biopathological parameters, particularly a high proliferative index, the present results indicate that it is possible to of identify tumors scoring 1+ by IHC with HER2 amplification by FISH, thus aiding the selection of patients who are suitable for HER2-targeted therapy according to an acceptable cost/benefit ratio.}, } @article {pmid27899433, year = {2017}, author = {McGilton, KS and Rochon, E and Sidani, S and Shaw, A and Ben-David, BM and Saragosa, M and Boscart, VM and Wilson, R and Galimidi-Epstein, KK and Pichora-Fuller, MK}, title = {Can We Help Care Providers Communicate More Effectively With Persons Having Dementia Living in Long-Term Care Homes?.}, journal = {American journal of Alzheimer's disease and other dementias}, volume = {32}, number = {1}, pages = {41-50}, pmid = {27899433}, issn = {1938-2731}, mesh = {Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Dementia/*nursing ; Feasibility Studies ; Female ; Humans ; *Long-Term Care ; Male ; Middle Aged ; *Nursing Homes ; *Outcome and Process Assessment, Health Care ; *Professional-Patient Relations ; *Quality of Life ; }, abstract = {BACKGROUND: Effective communication between residents with dementia and care providers in long-term care homes (LTCHs) is essential to resident-centered care.

PURPOSE: To determine the effects of a communication intervention on residents' quality of life (QOL) and care, as well as care providers' perceived knowledge, mood, and burden.

METHOD: The intervention included (1) individualized communication plans, (2) a dementia care workshop, and (3) a care provider support system. Pre- and postintervention scores were compared to evaluate the effects of the intervention. A total of 12 residents and 20 care providers in an LTCH participated in the feasibility study.

RESULTS: The rate of care providers' adherence to the communication plans was 91%. Postintervention, residents experienced a significant increase in overall QOL. Care providers had significant improvement in mood and perceived reduced burden.

CONCLUSION: The results suggest that the communication intervention demonstrates preliminary evidence of positive effects on residents' QOL and care providers' mood and burden.}, } @article {pmid27896628, year = {2017}, author = {Jones, KM and Randtke, EA and Yoshimaru, ES and Howison, CM and Chalasani, P and Klein, RR and Chambers, SK and Kuo, PH and Pagel, MD}, title = {Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI.}, journal = {Molecular imaging and biology}, volume = {19}, number = {4}, pages = {617-625}, pmid = {27896628}, issn = {1860-2002}, support = {R01 CA197029/CA/NCI NIH HHS/United States ; T32 HL007955/HL/NHLBI NIH HHS/United States ; }, mesh = {Acidosis/*diagnostic imaging/pathology ; Animals ; Carcinoma, Ovarian Epithelial ; Cell Line, Tumor ; Computer Simulation ; Disease Models, Animal ; Humans ; *Magnetic Resonance Imaging ; Mice ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial/pathology ; Ovarian Neoplasms/pathology ; *Translational Research, Biomedical ; }, abstract = {PURPOSE: We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis.

PROCEDURES: A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer were compared with DCE MRI and histopathology.

RESULTS: The pHe maps of a flank model showed pHe measurements between 6.4 and 7.4, which matched with the expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the patient with metastatic ovarian cancer, the average pHe value of three adjacent tumors was 6.58, and the most reliable pHe measurements were obtained from the right posterior tumor, which favorably compared with DCE MRI and histopathological results. The average pHe of the kidney showed an average pHe of 6.73 units. The patient with high-grade invasive ductal carcinoma failed to accumulate sufficient agent to generate pHe measurements.

CONCLUSIONS: Optimized acidoCEST MRI generated pHe measurements in a flank tumor model and could be translated to the clinic to assess a patient with metastatic ovarian cancer.}, } @article {pmid27895758, year = {2016}, author = {Bian, T and Lin, Q and Wu, Z and Cui, C and Qi, C and Li, L and Su, X}, title = {Metaplastic carcinoma of the breast: Imaging and pathological features.}, journal = {Oncology letters}, volume = {12}, number = {5}, pages = {3975-3980}, pmid = {27895758}, issn = {1792-1074}, abstract = {Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of the present study was to investigate the imaging and pathological features of metaplastic carcinoma. The features identified on mammography and sonography were retrospectively reviewed in 13 women with metaplastic carcinoma of the breast. The results from the mammographs and sonographs were additionally evaluated using immunohistochemical staining for the expression of the estrogen receptor (ER) and progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (CerbB-2) and P53. The most common features observed in the mammographs were as follows: Irregular and oval shaped masses, 53.8 and 46.2%, respectively; spiculated and circumscribed margins, each 30.8%; and high and marginally high density masses, 69.2 and 30.8%, respectively. The most common sonography features observed were as follows: Hypoechoic masses, 84.6%; complex echogenicity, 76.9%; irregular, round and oval shaped masses, 69.2, 30.8 and 30.8%, respectively; indistinct and circumscribed margins, 53.8 and 46.2%, respectively; an abundant blood flow, 53.8%; and posterior acoustic enhancement, 61.5%. The immunohistochemical (IHC) profile for 13 patients demonstrated that ER was not expressed in 100% of patients, PR and CerbB-2 were not present in 92.3% of patients, and P53 was present in 63.6% of patients. Therefore, metaplastic carcinoma of the breast exhibits more benign IHC features compared with invasive ductal carcinoma. In addition, it may be challenging to diagnose patients that do not possess posterior acoustic enhancement or express hormone receptors from other types of breast cancer.}, } @article {pmid27890770, year = {2017}, author = {Woulfe, KC and Siomos, AK and Nguyen, H and SooHoo, M and Galambos, C and Stauffer, BL and Sucharov, C and Miyamoto, S}, title = {Fibrosis and Fibrotic Gene Expression in Pediatric and Adult Patients With Idiopathic Dilated Cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {23}, number = {4}, pages = {314-324}, pmid = {27890770}, issn = {1532-8414}, support = {R21 HL097123/HL/NHLBI NIH HHS/United States ; T35 HL007715/HL/NHLBI NIH HHS/United States ; T32 HL007171/HL/NHLBI NIH HHS/United States ; R01 HL126928/HL/NHLBI NIH HHS/United States ; R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; }, mesh = {Age Factors ; Cardiomyopathy, Dilated/*complications ; Child ; Female ; Fibrosis ; Galectin 3/analysis ; Gene Expression Profiling ; *Heart Failure/etiology/metabolism/pathology ; *Heart Ventricles/metabolism/pathology ; Humans ; Interleukin-1/analysis ; Male ; Matrix Metalloproteinase 2/analysis ; MicroRNAs/*genetics ; Middle Aged ; *Myocardium/metabolism/pathology ; Signal Transduction ; Statistics as Topic ; Tissue Inhibitor of Metalloproteinases/analysis ; }, abstract = {BACKGROUND: Although fibrosis seems to be prognostic for adverse outcomes in adults with idiopathic dilated cardiomyopathy (IDC), little is known about the prevalence and development of fibrosis in pediatric IDC hearts. We hypothesized that there is less activation of fibrosis at a molecular level in pediatric IDC hearts than in failing adult hearts.

METHODS AND RESULTS: Pediatric hearts were analyzed histologically to determine the prevalence of fibrosis. Left ventricular tissue from adult and pediatric IDC hearts and adult and pediatric nonfailing (NF) hearts were subjected to quantitative reverse-transcription polymerase chain reaction to study the expression of important mRNAs that affect fibrosis. We found age-specific differences between IDC and NF hearts in the regulation of noncoding galectin-3, Corin, matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitor of metalloproteinase (TIMP) 2, and TIMP-3. We also found markers that were similarly altered in both adult and pediatric IDC hearts (interleukin-1 receptor-like 1 receptor, TIMP-1, and TIMP-4). Finally, microRNAs 29a-c were significantly decreased in the pediatric IDC patients.

CONCLUSIONS: Pediatric IDC patients demonstrate age-specific differences in the molecular pathways implicated in fibrosis in the adult heart. At the ultrastructural level the unique gene expression pattern appears to limit fibrosis in the failing pediatric heart.}, } @article {pmid27886676, year = {2016}, author = {Kawashima, H and Ariizumi, T and Saijo, Y and Moriyama, M and Umezu, H and Ikeda, Y and Ogose, A and Endo, N}, title = {Chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.}, journal = {Cancer genetics}, volume = {209}, number = {11}, pages = {501-505}, doi = {10.1016/j.cancergen.2016.10.005}, pmid = {27886676}, issn = {2210-7762}, mesh = {Breast Neoplasms/*genetics/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*genetics/radiotherapy ; *Chromosome Aberrations ; Cytogenetic Analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Myoepithelioma/*genetics/radiotherapy/surgery ; Neoplasm Recurrence, Local/genetics/radiotherapy ; Neoplasms, Second Primary/genetics/radiotherapy ; }, abstract = {Myoepithelial carcinoma of the breast is an extremely rare tumor composed entirely of malignant spindle cells with myoepithelial differentiation. The majority of previously reported cases have mainly described the clinicopathological features of the disease, and few have presented cytogenetic data. We herein present the case of a 48-year-old woman who was admitted with a left-sided breast lump in the inner upper quadrant that was initially diagnosed as a myoepithelioma with potentially malignant disorder. At 12 months after resection, she complained about a newly developed solid mass in the subareolar region of the ipsilateral breast that was diagnosed as an invasive ductal carcinoma. In addition, 16 months after the initial admission, a re-growing remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial carcinoma was also observed in her left axillary region 11 months after local recurrence. A cytogenetic analysis showed recurring specific chromosomal alterations both in the locally recurrent and in the lymph-node metastatic lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + mar1. To our knowledge, this is the first published report of clonal chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.}, } @article {pmid27878066, year = {2016}, author = {Min Kim, J and Young Kim, S and Hye Oh, M and Eun Lee, J}, title = {A Rare Case of Invasive Apocrine Carcinoma of the Breast with Unusual Radiologic Findings.}, journal = {Iranian journal of radiology : a quarterly journal published by the Iranian Radiological Society}, volume = {13}, number = {3}, pages = {e35298}, pmid = {27878066}, issn = {1735-1065}, abstract = {Invasive apocrine carcinoma (IAC) of the breast is a rare subtype of breast malignancy. Its incidence is not well known, but it is approximately less than 1% to 4%. For these reasons, there are few reports and little information on the radiologic appearance of IAC. Furthermore, most of the case reports show malignant features which are similar to invasive ductal carcinoma (IDC). We present a rare case of IAC without typical malignant feature on mammography, and ultrasonography (USG). Imaging findings on computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT are also presented. The nodule in our case showed a relatively benign feature on USG and it is the first case of IAC with unusual findings. Therefore, this report may encourage radiologists to consider the malignant potential and perform pathologic correlation even if a newly developed nodule does not present with a typical malignant feature on USG.}, } @article {pmid27870335, year = {2016}, author = {Ma, XL and Kang, L and Li, BJ and He, CN and Zhao, HF}, title = {Invasive Ductal Carcinoma Displayed "Basal-Like" Feature Arising within a Breast Fibroadenoma.}, journal = {The breast journal}, volume = {22}, number = {6}, pages = {695-696}, doi = {10.1111/tbj.12666}, pmid = {27870335}, issn = {1524-4741}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Fibroadenoma/*diagnostic imaging/pathology ; Humans ; Mammography ; Middle Aged ; Ultrasonography, Mammary ; }, } @article {pmid27866023, year = {2017}, author = {Takagi, H and Ando, T and Umemoto, T and , }, title = {Direct and adjusted indirect comparisons of perioperative mortality after sutureless or rapid-deployment aortic valve replacement versus transcatheter aortic valve implantation.}, journal = {International journal of cardiology}, volume = {228}, number = {}, pages = {327-334}, doi = {10.1016/j.ijcard.2016.11.253}, pmid = {27866023}, issn = {1874-1754}, mesh = {Aortic Valve Stenosis/diagnostic imaging/mortality/*surgery ; Cardiac Catheterization/methods ; Female ; Humans ; Male ; *Patient Safety ; Prognosis ; Randomized Controlled Trials as Topic ; Survival Analysis ; }, abstract = {OBJECTIVES: To determine which procedure, aortic valve replacement (AVR) with a sutureless or rapid-deployment prosthesis (SL-AVR) or transcatheter aortic valve implantation (TAVI), achieves better perioperative survival for severe aortic stenosis (AS), we conducted direct-comparison meta-analyses (DC-MAs) and an adjusted indirect-comparison meta-analysis (IDC-MA).

METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. Eligible studies were randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. We performed a DC-MA-[A] of SL-AVR versus TAVI, a DC-MA-[B] of SL-AVR versus conventional AVR (C-AVR), and a DC-MA-[C] TAVI versus C-AVR. Then, we computed a IDC-MA-[A'] of TAVI versus SL-AVR from the results of the DC-MA-[B] and the DC-MA-[C].

RESULTS: We identified 6 RCTs and 30 PSM studies enrolling a total of 15,887 patients. The 3 DC-MAs demonstrated significantly lower perioperative (30-day or in-hospital) all-cause mortality after SL-AVR than after TAVI (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.28 to 0.80; p=0.005) and no significant differences between SL-AVR and C-AVR (OR, 1.07; 95% CI, 0.60 to 1.94; p=0.81) and between TAVI and C-AVR (1.07; 95% CI, 0.90 to 1.27; p=0.45). The computed IDC-MA-[A'] indicated no significant difference in mortality between SL-AVR and TAVI (1.01; 95% CI, 0.54 to 1.86). Combining the results of the DC-MA-[A] and IDC-MA [A'] showed significantly lower mortality after SL-AVR than after TAVI (OR, 0.65; 95% CI, 0.44 to 0.97; p=0.03).

CONCLUSIONS: For patients with severe AS, SL-AVR may achieve better perioperative survival than TAVI.}, } @article {pmid27864452, year = {2017}, author = {Yeong, J and Thike, AA and Tan, PH and Iqbal, J}, title = {Identifying progression predictors of breast ductal carcinoma in situ.}, journal = {Journal of clinical pathology}, volume = {70}, number = {2}, pages = {102-108}, doi = {10.1136/jclinpath-2016-204154}, pmid = {27864452}, issn = {1472-4146}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Disease Progression ; Epithelial Cells/metabolism/pathology ; Extracellular Matrix/metabolism/pathology ; Female ; Humans ; Proteomics ; }, abstract = {Ductal carcinoma in situ (DCIS) refers to neoplastic epithelial cells proliferating within the mammary ducts of the breast, which have not breached the basement membrane nor invaded surrounding tissues. Traditional thinking holds that DCIS represents an early step in a linear progression towards invasive ductal carcinoma (IDC). However, as only approximately half of DCIS cases progress to IDC, important questions around the key determinants of malignant progression need to be answered. Recent studies have revealed that molecular differences between DCIS and IDC cells are not found at the genomic level; instead, altered patterns of gene expression and post-translational regulation lead to distinct transcriptomic and proteomic profiles. Therefore, understanding malignant progression will require a different approach that takes into account the diverse tumour cell extrinsic factors driving changes in tumour cell gene expression necessary for the invasive phenotype. Here, we review the roles of the tumour stroma (including mesenchymal cells, immune cells and the extracellular matrix) and myoepithelial cells in malignant progression and make a case for a more integrated approach to the study and assessment of DCIS and its progression, or lack thereof, to invasive disease.}, } @article {pmid27864119, year = {2017}, author = {Dai, H and Gallagher, D and Schmitt, S and Pessetto, ZY and Fan, F and Godwin, AK and Tawfik, O}, title = {Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.}, journal = {Human pathology}, volume = {61}, number = {}, pages = {68-77}, doi = {10.1016/j.humpath.2016.11.001}, pmid = {27864119}, issn = {1532-8392}, mesh = {Biomarkers, Tumor/classification/*genetics ; Biopsy ; Breast Neoplasms/blood/*genetics/mortality/pathology ; Carcinoma, Ductal, Breast/blood/*genetics/mortality/pathology ; Cell Proliferation ; Disease Progression ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; MicroRNAs/blood/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Phenotype ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Survival Analysis ; Tumor Burden ; }, abstract = {MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.}, } @article {pmid27862063, year = {2016}, author = {Tasharrofi, B and Soudyab, M and Nikpayam, E and Iranpour, M and Mirfakhraie, R and Sarrafzadeh, S and Geranpayeh, L and Azargashb, E and Sayad, A and Ghafouri-Fard, S}, title = {Comparative expression analysis of hypoxia-inducible factor-alpha and its natural occurring antisense in breast cancer tissues and adjacent noncancerous tissues.}, journal = {Cell biochemistry and function}, volume = {34}, number = {8}, pages = {572-578}, doi = {10.1002/cbf.3230}, pmid = {27862063}, issn = {1099-0844}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*genetics ; Child ; Demography ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism ; Middle Aged ; RNA, Antisense/*genetics/metabolism ; }, abstract = {Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.}, } @article {pmid27861897, year = {2017}, author = {Casasent, AK and Edgerton, M and Navin, NE}, title = {Genome evolution in ductal carcinoma in situ: invasion of the clones.}, journal = {The Journal of pathology}, volume = {241}, number = {2}, pages = {208-218}, pmid = {27861897}, issn = {1096-9896}, support = {R01 CA169244/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma in Situ/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics ; Disease Progression ; Female ; *Genomics ; Humans ; }, abstract = {Ductal carcinoma in situ (DCIS) is the most frequently diagnosed early-stage breast cancer. Only a subset of patients progress to invasive ductal carcinoma (IDC), and this presents a formidable clinical challenge for determining which patients to treat aggressively and which patients to monitor without therapeutic intervention. Understanding the molecular and genomic basis of invasion has been difficult to study in DCIS cancers due to several technical obstacles, including low tumour cellularity, lack of fresh-frozen tissues, and intratumour heterogeneity. In this review, we discuss the role of intratumour heterogeneity in the progression of DCIS to IDC in the context of three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. We examine the evidence in support of these models and their relevance to the diagnosis and treatment of patients with DCIS. We also discuss how emerging technologies, such as single-cell sequencing, STAR-FISH, and imaging mass spectrometry, are likely to provide new insights into the evolution of this enigmatic disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid27856072, year = {2017}, author = {Gesser-Edelsburg, A and Walter, N and Shir-Raz, Y and Sassoni Bar-Lev, O and Rosenblat, S}, title = {The behind-the-scenes activity of parental decision-making discourse regarding childhood vaccination.}, journal = {American journal of infection control}, volume = {45}, number = {3}, pages = {267-271}, doi = {10.1016/j.ajic.2016.10.009}, pmid = {27856072}, issn = {1527-3296}, mesh = {Adult ; Attitude to Health ; *Decision Making ; Female ; Humans ; Male ; Medication Adherence/*psychology ; Middle Aged ; Parents/*psychology ; *Patient Acceptance of Health Care ; Surveys and Questionnaires ; Vaccination/*psychology ; }, abstract = {BACKGROUND: Vaccine compliance has long been a cause for concern for health authorities throughout the world. However very little effort has been made to examine parental discourse during the decision-making process.

METHODS: An online survey was conducted (N = 437) to examine predictors of parents' attitudes regarding childhood vaccination.

RESULTS: Hesitant parents were 4 times more likely to conduct intrafamily discussion regarding vaccination compared with provaccination parents (Exp[B] = 4.26). There were no significant differences between hesitant and antivaccination parents with respect to intrafamily discussion. Hesitant parents were also 4 times more likely than provaccination parents to report intrafamily disagreements regarding vaccination (Exp[B] = 4.27). They were also twice as likely as antivaccination parents to express disagreements regarding vaccination within their families (Exp[B] = 2.33). Likewise, Jewish parents were significantly more likely to define themselves as vaccination-hesitant, whereas Muslim parents were significantly more likely to be provaccination.

CONCLUSIONS: To improve the way health organizations communicate information about vaccines and increase parental trust in immunization programs, we should not only look at the level of understanding, perceptions, and biases of different groups, but also thoroughly examine parents' decision-making processes and the discourse during this process. We must communicate risk to all groups, including the provaccination group, to improve parents' decision making and the process of informed consent.}, } @article {pmid27852170, year = {2017}, author = {Shai, D and Belsky, J}, title = {Parental embodied mentalizing: how the nonverbal dance between parents and infants predicts children's socio-emotional functioning.}, journal = {Attachment & human development}, volume = {19}, number = {2}, pages = {191-219}, doi = {10.1080/14616734.2016.1255653}, pmid = {27852170}, issn = {1469-2988}, mesh = {Child Behavior/*classification ; *Child Development ; Child, Preschool ; Family Characteristics ; Female ; Humans ; Infant ; Language Development ; Longitudinal Studies ; Male ; Mother-Child Relations/*psychology ; National Institute of Child Health and Human Development (U.S.) ; *Object Attachment ; Observation ; Observer Variation ; Parenting/*psychology ; Social Class ; Social Skills ; United States ; }, abstract = {Parental mentalizing - the parent's ability to envision the child's mental states (such as desires, thoughts, or wishes) - has been argued to underlie a parent's ability to respond sensitively to their child's emotional needs, and thereby promote advantageous cognitive and socio-emotional development. Mentalizing is typically operationalized in terms of how parents talk to or about their infants. This work extends research on mentalizing by operationalizing parental mentalizing exclusively in terms of nonverbal, bodily based, interactive behavior, namely parental embodied mentalizing(PEM). The purpose of the current research was twofold: (1) to establish the reliability and validity of the PEM coding system; and (2) to evaluate whether such measurement predicts infant and child cognitive and socio-emotional functioning. Assessing 200 mother-infant dyads at 6 months using the coding of PEM proved both reliable and valid, including predicting child attachment security at 15 and 36 months, and language abilities, academic skills, behavior problems, and social competence at 54 months, in many cases even after taking into consideration traditional measures of parenting, namely maternal sensitivity. Conceptual, empirical, and clinical implications are discussed.}, } @article {pmid27847402, year = {2016}, author = {Dyachenko, L and Havrysh, K and Lytovchenko, A and Dosenko, I and Antoniuk, S and Filonenko, V and Kiyamova, R}, title = {Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades.}, journal = {Disease markers}, volume = {2016}, number = {}, pages = {5128720}, pmid = {27847402}, issn = {1875-8630}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*blood/genetics/immunology ; Autoantibodies/*blood ; Base Sequence ; Biomarkers, Tumor/*blood/immunology ; Breast Neoplasms/blood/*immunology/pathology ; Carcinoma, Ductal, Breast/blood/immunology/pathology ; Carcinoma, Lobular/blood/immunology/pathology ; Carcinoma, Medullary/blood/immunology/pathology ; Case-Control Studies ; DNA-Binding Proteins/*blood/genetics/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Gene Library ; Humans ; Middle Aged ; Molecular Chaperones ; Neoplasm Grading ; Neoplasm Staging ; Nuclear Pore Complex Proteins/blood/genetics/immunology ; Oncogene Proteins/*blood/genetics/immunology ; Prognosis ; RNA-Binding Proteins/blood/genetics/immunology ; Young Adult ; }, abstract = {Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated.}, } @article {pmid27846863, year = {2016}, author = {Ohashi, R and Hayama, A and Yanagihara, K and Yamashita, K and Sakatani, T and Takei, H and Naito, Z}, title = {Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: a clinicopathological study.}, journal = {Diagnostic pathology}, volume = {11}, number = {1}, pages = {131}, pmid = {27846863}, issn = {1746-1596}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Signet Ring Cell/metabolism/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mucins/analysis/*biosynthesis ; Prognosis ; Transcriptome ; }, abstract = {BACKGROUND: Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6.

METHODS: Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters.

RESULTS: The series consisted of invasive ductal carcinoma (n = 9), invasive lobular carcinoma (n = 9), and mucinous carcinoma (n = 4) cases. The SRC population accounted for 8-81 % of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n = 12) and low (n = 10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n = 11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n = 11; p = 0.01, p = 0.002, p = 0.008, and p = 0.02, respectively). The CM group (n = 7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67 indices than the LC group (n = 15; p = 0.04, p = 0.001, p = 0.006, and p = 0.03, respectively). The expression levels of MUC2, MUC4, MUC5AC, and MUC6 showed no clinicopathological significance. Two patients with low MUC1 expression and CM patterns had tumor recurrence, resulting in death, while all the other patients survived without recurrence.

CONCLUSION: Our results demonstrate that in breast cancers containing SRCs, low MUC1 expression and/or its CM subcellular localization patterns are associated with unfavorable clinicopathological factors. The utility of MUC1 expression as a prognostic marker remains to be verified in future studies.}, } @article {pmid27845674, year = {2017}, author = {Chen, TA and Wu, WJ and Wei, CL and Darling, RB and Liu, BD}, title = {Novel 10-Bit Impedance-to-Digital Converter for Electrochemical Impedance Spectroscopy Measurements.}, journal = {IEEE transactions on biomedical circuits and systems}, volume = {11}, number = {2}, pages = {370-379}, doi = {10.1109/TBCAS.2016.2592511}, pmid = {27845674}, issn = {1940-9990}, mesh = {*Dielectric Spectroscopy ; *Electric Impedance ; *Signal Processing, Computer-Assisted ; }, abstract = {Electrochemical impedance spectroscopy (EIS) is a widely used technique in biomedical and chemical analysis. A novel 10-bit impedance-to-digital converter (IDC), which can measure and directly convert the magnitude and phase of impedance to digital codes, is proposed for the EIS measurement system. The proposed IDC is composed of a magnitude-to-digital converter (MDC) and a phase-to-digital converter (PDC). The proposed IDC was designed and fabricated using a 0.35 [Formula: see text] 2P4M mixed-signal polycide process, and the core area is only 0.07 mm[2]. Moreover, it can work over a very wide frequency range (0.1 mHz-100 kHz), and has excellent accuracy. According to the measured results, the DNL of the MDC is within -0.3/+0.3 LSB, and the INL is around -3/+1 LSB. Moreover, an EIS measurement system, which is composed of the proposed IDC chip and some other commercial chips, is built to measure ZoBell's and melatonin solutions for validating the function of the proposed IDC.}, } @article {pmid27844173, year = {2017}, author = {Santangelo, G and Raimo, S and Siciliano, M and D'Iorio, A and Piscopo, F and Cuoco, S and Bottone, M and Trojsi, F and Grossi, D and Trojano, L}, title = {Assessment of apathy independent of physical disability: validation of the Dimensional Apathy Scale in Italian healthy sample.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {38}, number = {2}, pages = {303-309}, pmid = {27844173}, issn = {1590-3478}, mesh = {Adolescent ; Adult ; Aged ; Apathy/*physiology ; Female ; Humans ; Italy ; Male ; Middle Aged ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*instrumentation ; Reproducibility of Results ; Young Adult ; }, abstract = {Apathy is well described in neurodegenerative diseases characterized by motor disability; therefore, assessment of apathy avoiding possible confounding effects of motor impairments is necessary in neurological diseases. Recently, the Dimensional Apathy Scale (DAS) was developed to assess apathy as multifaceted construct, independent of physical disability. We developed the Italian version of the Dimensional Apathy Scale (I-DAS) and explored its psychometric properties in a sample of 309 healthy individuals. Participants also completed Apathy Evaluation Scale, Beck Depression Inventory-II and Addenbrooke's Cognitive Examination-Revised. The I-DAS showed high internal consistency, good convergent and divergent validity. The I-DAS had a three-factor structure, such as the original scale. The I-DAS scored was significantly correlated with individuals' education, but not with age or gender. We, therefore, computed correction factor for education and provided percentile distribution of the adjusted scores to identify individuals with high levels of apathy. The I-DAS showed good psychometric properties and can be a valid and reliable tool to assess multidimensional apathy.}, } @article {pmid27842678, year = {2016}, author = {Seithe, T and Braun, J and Wolf, M and Vahldiek, J and Wolny, D and Auer, J and Pociej, J and Heine, O and Hamm, B and de Bucourt, M}, title = {Diagnostic efficacy and safety of gadoteric acid MR mammography in 1537 patients.}, journal = {European journal of radiology}, volume = {85}, number = {12}, pages = {2281-2287}, doi = {10.1016/j.ejrad.2016.10.013}, pmid = {27842678}, issn = {1872-7727}, mesh = {Administration, Intravenous ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/*diagnostic imaging ; Breast Neoplasms/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; *Contrast Media/administration & dosage/adverse effects ; Deglutition Disorders/chemically induced ; Early Detection of Cancer ; Exanthema/chemically induced ; Female ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Male ; *Meglumine/administration & dosage/adverse effects ; Middle Aged ; *Organometallic Compounds/administration & dosage/adverse effects ; Product Surveillance, Postmarketing ; Safety ; Tachycardia/chemically induced ; Urticaria/chemically induced ; Young Adult ; }, abstract = {OBJECTIVES: To perform a large-scale multicenter post-marketing surveillance study for analyzing diagnostic effectiveness and safety of intravenous (IV) gadoteric acid (Dotarem[®]) in magnetic resonance (MR) mammography under daily practice conditions.

MATERIALS AND METHODS: Patients underwent high-resolution MR mammography with gadoteric acid in 15 German centers. Radiologists used a standardized questionnaire to report data including patient demographics and medical history, characteristics of MR examination and results in terms of diagnosis and safety for the patient.

RESULTS: A total of 1537 patients were examined. In 99.2% of all patients, a diagnosis was established. In 91.6% of all patients, image quality was excellent or good. Histopathological examinations were performed for 232 of 1537 patients (15.1%) with invasive ductal carcinoma being the most frequent diagnosis (109 patients, 47.0%). Based on histopathology as the standard of reference, IV gadoteric acid-enhanced MR mammography confirmed diagnoses of invasive ductal carcinoma in 93.5% of the patients. Adverse drug reactions occurred in 5 of 1537 patients (0.3%) and were classified as serious in one case (tachycardia, dysphagia, urticaria, rash). All patients with adverse drug reactions fully recovered after the examination.

CONCLUSION: This noninterventional surveillance study shows IV gadoteric acid to be a safe and effective contrast agent for use in MR mammography.}, } @article {pmid27842327, year = {2016}, author = {Seijo, E and Lima, D and Iriabho, E and Almeida, J and Monico, J and Echeverri, M and Gutierrez, S and Flores, I and Lee, JH and Fisher, K and Grizzle, WE and Sica, GL and Butler, C and Hicks, C and Meade, CD and Sodeke, SO and Moroz, K and Coppola, D and Munoz-Antonia, T}, title = {Construction and Validation of a Multi-Institutional Tissue Microarray of Invasive Ductal Carcinoma From Racially and Ethnically Diverse Populations.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {23}, number = {4}, pages = {383-389}, pmid = {27842327}, issn = {1526-2359}, support = {U54 CA118638/CA/NCI NIH HHS/United States ; UM1 CA183728/CA/NCI NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; G12 MD007585/MD/NIMHD NIH HHS/United States ; U56 CA118809/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; U54 CA118623/CA/NCI NIH HHS/United States ; U54 CA153509/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*epidemiology ; Ethnicity ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Tissue Array Analysis ; }, abstract = {BACKGROUND: The scarcity of tissues from racial and ethnic minorities at biobanks poses a scientific constraint to research addressing health disparities in minority populations.

METHODS: To address this gap, the Minority Biospecimen/Biobanking Geographic Management Program for region 3 (BMaP-3) established a working infrastructure for a "biobanking" hub in the southeastern United States and Puerto Rico. Herein we describe the steps taken to build this infrastructure, evaluate the feasibility of collecting formalin-fixed, paraffin-embedded tissue blocks and associated data from a single cancer type (breast), and create a web-based database and tissue microarrays (TMAs).

RESULTS: Cancer registry data from 6 partner institutions were collected, representing 12,408 entries from 8,279 unique patients with breast cancer (years 2001-2011). Data were harmonized and merged, and deidentified information was made available online. A TMA was constructed from formalin-fixed, paraffin-embedded samples of invasive ductal carcinoma (IDC) representing 427 patients with breast cancer (147 African Americans, 168 Hispanics, and 112 non-Hispanic whites) and was annotated according to biomarker status and race/ethnicity. Biomarker analysis of the TMA was consistent with the literature.

CONCLUSIONS: Contributions from participating institutions have facilitated a robust research tool. TMAs of IDC have now been released for 5 projects at 5 different institutions.}, } @article {pmid27840910, year = {2016}, author = {Gomulkiewicz, A and Jablonska, K and Pula, B and Grzegrzolka, J and Borska, S and Podhorska-Okolow, M and Wojnar, A and Rys, J and Ambicka, A and Ugorski, M and Zabel, M and Dziegiel, P}, title = {Expression of metallothionein 3 in ductal breast cancer.}, journal = {International journal of oncology}, volume = {49}, number = {6}, pages = {2487-2497}, doi = {10.3892/ijo.2016.3759}, pmid = {27840910}, issn = {1791-2423}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Immunohistochemistry ; MCF-7 Cells ; Metallothionein 3 ; Middle Aged ; Nerve Tissue Proteins/biosynthesis/genetics/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.}, } @article {pmid27840759, year = {2016}, author = {Marinova, L and Malinova, D and Vicheva, S}, title = {Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2016}, number = {}, pages = {6762085}, pmid = {27840759}, issn = {2090-6781}, abstract = {We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status.}, } @article {pmid27837612, year = {2016}, author = {Ilic, IR and Djordjevic, NP and Randjelovic, PJ and Stojanovic, NM and Radulovic, NS and Ilic, RS}, title = {Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {5}, pages = {1113-1120}, pmid = {27837612}, issn = {1107-0625}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/epidemiology/*pathology ; Carcinoma, Lobular/*chemistry/epidemiology/*pathology ; Female ; Health Care Surveys ; Humans ; *Immunohistochemistry ; Incidence ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Serbia/epidemiology ; Time Factors ; }, abstract = {PURPOSE: The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia.

METHODS: Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared.

RESULTS: Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant.

CONCLUSIONS: Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.}, } @article {pmid27837608, year = {2016}, author = {Panagiotopoulos, N and Lagoudianakis, E and Pappas, A and Filis, K and Salemis, N and Manouras, A and Kontzoglou, K and Zografos, G}, title = {Lymphovascular infiltration in the tumor bed is a useful marker of biological behavior in breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {5}, pages = {1082-1089}, pmid = {27837608}, issn = {1107-0625}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Blood Vessels/chemistry/*pathology ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Lymphatic Vessels/chemistry/*pathology ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: Tumor cells can metastasize by entering existing vessels or new vessels actively recruited into the primary tumor. Invasion of the lymphatics and blood vessels in the periphery of the tumor seems to be a prerequisite step in the metastatic process. The aim of this study was to correlate peripheral lymphatic vessel infiltration (PLI) and peripheral blood vessel infiltration (PVI) in a cohort of patients with invasive ductal carcinoma of the breast with various other prognostic parameters and outcome.

METHODS: The study population consisted of 236 female patients with invasive ductal breast carcinomas, who had been operated between 2011 and 2013. The registered data included age at diagnosis, histological subtype, tumor size, TNM stage, histological grade, estrogen (ER) and progesterone receptors (PR), HER-2, p53, and PLI and PVI.

RESULTS: Pathological examination revealed that 22.5% of the patients had PVI and 37.3% had PLI at the tumor front. PVI correlated with younger age (p<0.05), higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05), higher N stage (p<0.05) and positive Ki67 expression (p<0.05). Similarly, PLI correlated with higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05) and higher N stage (p<0.05). Statistical analysis did not reveal significant correlation between the presence of tumor blood and lymphatic vessels with infiltration in overall (OS) and disease-free survival (DFS).

CONCLUSIONS: PLI and PVI are important markers of worse clinical outcome as shown by their association with other established factors, but no association with recurrence and survival could be proven.}, } @article {pmid27837296, year = {2017}, author = {Timbrell, S and Al-Himdani, S and Shaw, O and Tan, K and Morris, J and Bundred, N}, title = {Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.}, journal = {Annals of surgical oncology}, volume = {24}, number = {4}, pages = {1071-1076}, pmid = {27837296}, issn = {1534-4681}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Margins of Excision ; Mastectomy, Simple/*methods ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm, Residual ; Organ Sparing Treatments ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher.

METHODS: To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010.

RESULTS: In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p = 0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins.

CONCLUSIONS: These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.}, } @article {pmid27835573, year = {2016}, author = {Sang, J and Yi, D and Tang, X and Zhang, Y and Huang, T}, title = {The associations between mast cell infiltration, clinical features and molecular types of invasive breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {49}, pages = {81661-81669}, pmid = {27835573}, issn = {1949-2553}, mesh = {Age Factors ; Breast Neoplasms/chemistry/classification/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/classification/*pathology/therapy ; Carcinoma, Lobular/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Lymphatic Metastasis ; Mast Cells/chemistry/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; Tumor Burden ; }, abstract = {Associations between mast cell infiltration and the clinical features and known molecular profile of breast cancer remain unclear. The distribution difference of mast cell was evaluated, in 219 patients with no special type of invasive carcinoma, using sorts of age, max diameter of cancer, histological type, lymph node metastasis as well as the expressions of estrogen receptor (ER), progestogen receptor (PR), human epidermal growth factor receptor 2 (HER-2) and nuclear protein Ki67. The mast cell density (MCD) in patients younger than 50 years old was significantly higher than that in patients with age ≥ 50. The MCD in ER or PR positive patients was significantly higher than MCD in ER or PR negative patients. The MCD in patients with Ki67 ≤ 14% was also significantly higher than MDC in patients with Ki67 > 14%. The MCD of patients with invasive ductal carcinoma was significantly higher than MCD of patients with invasive lobular carcinoma. No significant distribution difference of MCD was found to be associated with max diameter of cancer, lymph node metastasis and HER-2. Further analysis found that MDC was significantly higher in patients after neo-adjuvant chemotherapy. The distribution difference of mast cell widely exists in patients with distinct clinical features, the role of mast cell in breast cancer need further research with detailed and reasonable classification to clarify.}, } @article {pmid27827363, year = {2016}, author = {Ekim Üstünel, B and Friedrich, K and Maida, A and Wang, X and Krones-Herzig, A and Seibert, O and Sommerfeld, A and Jones, A and Sijmonsma, TP and Sticht, C and Gretz, N and Fleming, T and Nawroth, PP and Stremmel, W and Rose, AJ and Berriel-Diaz, M and Blüher, M and Herzig, S}, title = {Control of diabetic hyperglycaemia and insulin resistance through TSC22D4.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {13267}, pmid = {27827363}, issn = {2041-1723}, mesh = {Animals ; Blood Glucose/*metabolism ; Cell Line ; Diabetes Mellitus, Type 2/blood/*genetics ; Female ; Gene Expression Regulation ; Humans ; Hyperglycemia/blood/*genetics ; Insulin Resistance/*genetics ; Lipocalins/genetics/metabolism ; Liver/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Transcription Factors/*genetics/metabolism ; }, abstract = {Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis-at least in part-through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy.}, } @article {pmid27825140, year = {2017}, author = {Lu, DG and Ma, YM and Zhu, AJ and Han, YW}, title = {An early biomarker and potential therapeutic target of RUNX 3 hypermethylation in breast cancer, a system review and meta-analysis.}, journal = {Oncotarget}, volume = {8}, number = {13}, pages = {22166-22174}, pmid = {27825140}, issn = {1949-2553}, mesh = {Animals ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/*genetics ; Core Binding Factor Alpha 3 Subunit/*genetics ; *DNA Methylation ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; }, abstract = {Runt-related transcription factor 3 (RUNX3) methylation plays an important role in the carcinogenesis of breast cancer (BC). However, the association between RUNX3 hypermethylation and significance of BC remains under investigation. The purpose of this study is to perform a meta-analysis and literature review to evaluate the clinicopathological significance of RUNX3 hypermethylation in BC. A comprehensive literature search was performed in Medline, Web of Science, EMBASE, Cochrane Library Database, CNKI and Google scholar. A total of 10 studies and 747 patients were included for the meta-analysis. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were evaluated and summarized respectively. RUNX3 hypermethylation was significantly correlated with the risk of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), OR was 50.37, p < 0.00001 and 22.66, p < 0.00001 respectively. Interestingly, the frequency of RUNX3 hypermethylation increased in estrogen receptor (ER) positive BC, OR was 12.12, p = 0.005. High RUNX3 mRNA expression was strongly associated with better relapse-free survival (RFS) in BC patients. In summary, RUNX3 methylation could be a promising early biomarker for the diagnosis of BC. High RUNX3 mRNA expression is correlated to better RFS in BC patients. RUNX3 could be a potential therapeutic target for the development of personalized therapy.}, } @article {pmid27822759, year = {2016}, author = {Autenshlyus, AI and Kunts, TA and Karpukhina, KV and Mikhaylova, ES and Varaksin, NA and Marinkin, IO and Lyakhovich, VV}, title = {Cytokine pattern of the breast tumor supernatant.}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {470}, number = {1}, pages = {247-248}, pmid = {27822759}, issn = {1608-3105}, mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Cell Fractionation ; Cytokines/*immunology ; Female ; Fibroadenoma/*immunology ; Humans ; Inflammation Mediators/*immunology ; Tumor Cells, Cultured ; Tumor Microenvironment/*immunology ; }, abstract = {Cytokine production was evaluated in supernatants of cultured tumor cells that were obtained by biopsy of the breast invasive ductal carcinoma (IDC) and breast fibroadenoma (FA) and grown in vitro. In the IDC supernatants, the concentrations of pro-inflammatory (pro-oncogenic) cytokines IL-17, IL-18, and IFNγ and of IL-1 receptor antagonist were significantly higher than in the FA cell supernatants. The concentrations of anti-inflammatory cytokine IL-10 and MCP-1 protein in supernatants of IDC cells were significantly lower than those determined in FA supernatants.}, } @article {pmid27754691, year = {2016}, author = {Dai, Q and Li, P and Ma, N and Hu, C}, title = {Palladium-Catalyzed Decarboxylative Synthesis of Arylamines.}, journal = {Organic letters}, volume = {18}, number = {21}, pages = {5560-5563}, doi = {10.1021/acs.orglett.6b02724}, pmid = {27754691}, issn = {1523-7052}, abstract = {A novel approach has been developed for the synthesis of arylamines via the palladium-catalyzed intramolecular decarboxylative coupling (IDC) of aroyloxycarbamates, obtained in situ by reacting aryl carboxylic acids with hydroxycarbamates. The reaction offers facile access to structurally diverse arylamines with the site-specific formation of the C(sp[2])-N bond under mild conditions.}, } @article {pmid27681506, year = {2017}, author = {Zhao, Z and Chen, X and Hao, S and Jia, R and Wang, N and Chen, S and Li, M and Wang, C and Mao, H}, title = {Increased interleukin-35 expression in tumor-infiltrating lymphocytes correlates with poor prognosis in patients with breast cancer.}, journal = {Cytokine}, volume = {89}, number = {}, pages = {76-81}, doi = {10.1016/j.cyto.2016.09.012}, pmid = {27681506}, issn = {1096-0023}, mesh = {Adult ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*metabolism/*mortality/pathology/therapy ; Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Interleukins/*biosynthesis ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Survival Rate ; T-Lymphocytes, Regulatory/*metabolism/pathology ; }, abstract = {Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay. IL-35 expression in the tissue specimens was analyzed by immunohistochemistry. It was shown that 39.1%, 43.6% and 17.3% of the 110 patients were absent, weak, and strong IL-35 expression in the TILs, respectively. Strong IL-35 expression in TILs was significantly associated with age >50years, tumor size >2cm, TNM stage III, and negative ER (All P<0.05). Patients with elevated IL-35 expression in TILs had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with weak or no IL-35 expression (All P<0.05). High plasma IL-35 levels were significantly associated with TNM stage III and lymph node metastasis (All P<0.05). Plasma IL-35 level and IL-35 expression in the TILs of breast cancer tissues may be a valuable biomarker in the development and prognosis of IDC.}, } @article {pmid27622969, year = {2016}, author = {Moccia, M and Erro, R and Picillo, M and Vitale, C and Longo, K and Amboni, M and Pellecchia, MT and Barone, P}, title = {Caffeine consumption and the 4-year progression of de novo Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {32}, number = {}, pages = {116-119}, doi = {10.1016/j.parkreldis.2016.08.005}, pmid = {27622969}, issn = {1873-5126}, mesh = {Aged ; Antiparkinson Agents/therapeutic use ; Caffeine/*metabolism ; Cohort Studies ; Disease Progression ; Female ; Humans ; Kaplan-Meier Estimate ; Levodopa/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/drug therapy/*physiopathology ; Proportional Hazards Models ; Quality of Life ; Surveys and Questionnaires ; Time Factors ; }, abstract = {INTRODUCTION: Higher caffeine consumption has been associated with reduced risk of Parkinson's disease (PD), and with a more benign progression of motor and non-motor symptoms (NMS). The present observational cohort study investigated motor and non-motor correlates of caffeine consumption in de novo PD.

METHODS: 79 newly diagnosed, drug naïve PD patients have been included and followed up for 4 years. The total caffeine use was calculated with the Caffeine Consumption Questionnaire. Following study variables were recorded at baseline, and after 2 and 4 years: UPDRS part III, UPDRS part IV, l-dopa Equivalent Daily Dose (LEDD), NMS Questionnaire (NMSQuest), and the time occurring from PD diagnosis to the need for l-dopa treatment. Age, gender and disease duration were included as covariates in the statistical models.

RESULTS: The average daily caffeine consumption was 296.1 ± 157.2 mg. At Cox regression models, higher caffeine consumption was associated with a lower rate of starting l-Dopa treatment (HR = 0.630; 95%CI = 0.382-0.996). At the mixed-effects linear regression models considering the whole study period, each additional espresso cup per day (50 mg of caffeine) was more likely associated with 5-point lower UPDRS part III total score (Coef = -0.01; 95%CI = -0.02 to 0.00), with 50% reduced LEDD (Coef = -0.01; 95%CI = -0.15 to 0.00; p = 0.021), and with 5-point lower NMSQuest total score (Coef = -0.01; 95%CI = -0.01 to 0.00), but not with UPDRS part IV total score (Coef = -0.00; 95%CI = -0.00 to 0.00).

CONCLUSION: Caffeine consumption was associated with a reduced accrual of motor and non-motor disability during 4-year follow-up in de novo PD, highlighting the rationale for using adenosine A2A antagonists since the early phases of PD.}, } @article {pmid27613186, year = {2016}, author = {Ilahi, NE and Anwar, S and Noreen, M and Hashmi, SN and Murad, S}, title = {Detection of human papillomavirus-16 DNA in archived clinical samples of breast and lung cancer patients from North Pakistan.}, journal = {Journal of cancer research and clinical oncology}, volume = {142}, number = {12}, pages = {2497-2502}, pmid = {27613186}, issn = {1432-1335}, mesh = {Adult ; Aged ; Breast Neoplasms/complications/epidemiology/*virology ; DNA, Viral/*isolation & purification ; Female ; Human papillomavirus 16/genetics/*isolation & purification ; Humans ; Lung Neoplasms/complications/epidemiology/*virology ; Middle Aged ; Pakistan/epidemiology ; Papillomavirus Infections/*complications/epidemiology/genetics ; Prevalence ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded as a key player in the development of various genital cancers, most notably cervical cancer. It has also been associated with some non-genital cancers. A subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological involvement has been suggested for breast and lung cancer as well. However, reports regarding the HPV DNA detection vary widely from different parts of the world. Due to scarcity of local data in this regard, the current study aimed at retrospective detection of HPV presence in the archival samples of breast and lung cancer patients from north part of the country.

METHODS: A total of 55 formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of breast (n = 46) and lung (n = 9) were collected for this study. Genotyping for HPV16 and 18 was carried out through PCR.

RESULTS: HPV16 DNA was found in both breast and lung carcinoma samples with the prevalence rate of 17 and 11 %, respectively. An interesting association was found between ER/PR (Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor receptor-2) positivity with HPV occurrence in breast tumours.

CONCLUSION: Current study shows the presence of HPV16 DNA in archived clinical biopsy sections from breast and lung cancers (17, 11 %), respectively. A positive correlation of HPV16 presence was found with ER/PR and HER2-positive breast cancers. These initial findings warrant further investigation in order to determine HPV prevalence and aetiological role in local cancers, especially in ER/PR/HER2-positive breast cancers on a larger scale.}, } @article {pmid27806851, year = {2016}, author = {Boruah, D and Bhatia, JK and Rai, A and Srinivas, V and Nijhawan, VS}, title = {Correlation of microvessel parameters in invasive ductal carcinoma of the breast and fibroadenomas: a morphometric study.}, journal = {Annals of diagnostic pathology}, volume = {25}, number = {}, pages = {72-78}, doi = {10.1016/j.anndiagpath.2016.09.014}, pmid = {27806851}, issn = {1532-8198}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/blood supply/diagnosis/*pathology ; Carcinoma, Ductal, Breast/blood supply/*pathology ; Female ; Fibroadenoma/diagnosis/*pathology ; Humans ; Microvessels/*pathology ; Middle Aged ; Neovascularization, Pathologic/*pathology ; Young Adult ; }, abstract = {Modifications of microvascular configuration are essential features encountered during the progression of breast tumors. Our objectives were to correlate morphometrically evaluated microvessel parameters (microvessel density [MVD], microvessel caliber [VC], microvessel cross-sectional area [VCSA], percentage of total VCSA [%TVCSA], and total microvessel boundary density [TVBD]) with histologic grades of invasive ductal carcinoma (IDC) of the breast and benign breast lesions. Sixty cases of IDC presented with modified radical mastectomy, and 20 benign breast fibroadenomas were evaluated for various microvessel parameters, using CD34-immunostained histologic sections by computerized image morphometry. Samples were divided into 4 histologic groups: benign, grade 1, grade 2, and grade 3; mean with SD and range was evaluated for each group. Histologic grades showed a strong positive correlation with %TVCSA (ρ=0.773) and TVBD (ρ=0.811) and a moderate positive correlation with MVD (ρ=0.607), VC (ρ=0.609), and VCSA (ρ=0.616) when analyzed for all samples of the 4 groups. Except MVD, all parameters including age was the lowest (P<.001) for the benign group. Among the IDCs, differences of mean VC and VCSA were not significant; MVD, %TVCSA, and TVBD were the lowest in grade 1 and the highest in grade 3. Upper cutoff value of benign lesions for MVD was 155mm[-2]; VC, 9.94μm; VCSA, 94.42 μm[2]; %TVCSA, 1.33; and TVBD, 4.37mm[-1]. Total microvessel boundary density included the information of microvessel concentration and size showed the best correlation with grades. Microvessel density showed a positive correlation with grades in the IDCs, but for the differentiation of benign from malignant, VC, VCSA, %TVCSA, and TVBD showed excellent area under the receiver operating characteristic curve (area under the curve > 0.990), unlike MVD (area under the curve = 0.797).}, } @article {pmid27806840, year = {2016}, author = {Calhoun, BC and Collie, AM and Lott-Limbach, AA and Udoji, EN and Sieck, LR and Booth, CN and Downs-Kelly, E}, title = {Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management.}, journal = {Annals of diagnostic pathology}, volume = {25}, number = {}, pages = {20-25}, doi = {10.1016/j.anndiagpath.2016.07.009}, pmid = {27806840}, issn = {1532-8198}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/methods ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma in Situ/*pathology/*therapy ; Carcinoma, Lobular/diagnosis/*pathology ; Female ; Humans ; Hyperplasia/diagnosis/pathology ; Mammography ; Middle Aged ; Precancerous Conditions/pathology ; }, abstract = {The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n=1), invasive lobular carcinoma (n=4), ductal carcinoma in situ (n=3), and pleomorphic lobular carcinoma in situ (n=2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.}, } @article {pmid27800068, year = {2016}, author = {Ziyadi, M and Boujoual, M and Raiteb, H and Babahabib, MA and Kouach, J and Moussaoui, DR and Dehayni, M}, title = {[Squamous cell carcinoma of the breast: report of a case and review of the literature].}, journal = {The Pan African medical journal}, volume = {24}, number = {}, pages = {213}, pmid = {27800068}, issn = {1937-8688}, mesh = {Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Squamous Cell/diagnosis/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; }, abstract = {Squamous cell carcinoma of the breast is a rare tumour of metaplasic origin; etiopathogeny is controversial; diagnosis is based on histological examination after eliminating the primary tumor; clinical and radiological examination is not specific; treatment is the same as for invasive ductal carcinoma; prognisis is poor due to tumor size and lymph node involvement. We report a case of breast squamous cell carcinoma in a 39 years old patient who was examined in the obstetrics and gynecology department of the military hospital in Rabat. Patient observation allowed us to specify the clinical characteristics of this entity which remains rare.}, } @article {pmid27798919, year = {2016}, author = {Fujii, T and Yajima, R and Kurozumi, S and Higuchi, T and Obayashi, S and Tokiniwa, H and Nagaoka, R and Takata, D and Horiguchi, J and Kuwano, H}, title = {Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.}, journal = {Anticancer research}, volume = {36}, number = {10}, pages = {5481-5485}, doi = {10.21873/anticanres.11129}, pmid = {27798919}, issn = {1791-7530}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Fluorodeoxyglucose F18/*administration & dosage ; Humans ; Middle Aged ; Positron-Emission Tomography/*methods ; Retrospective Studies ; }, abstract = {The diagnostic utility of [18]F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUVmax) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUVmax was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUVmax and tumor size and between SUVmax and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients.}, } @article {pmid27797262, year = {2016}, author = {Thanasitthichai, S and Chaiwerawattana, A and Phadhana-Anake, O}, title = {Impact of Using Intra-Operative Ultrasound Guided Breast- Conserving Surgery on Positive Margin and Re-Excision Rates in Breast Cancer Cases with Current SSO/ASTRO Guidelines.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {9}, pages = {4463-4467}, pmid = {27797262}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Carcinoma, Lobular/pathology/surgery ; Female ; Frozen Sections/methods ; Humans ; Mastectomy, Segmental/methods ; Middle Aged ; Reoperation/methods ; Retrospective Studies ; Thailand ; Ultrasonography/methods ; }, abstract = {PURPOSE: To review the impact of using intra-operative ultrasound guided breast conserving surgery with frozen sections on nal pathological margin outcome with the current guidelines set forth by the Society of Surgical Oncology (SSO) and the American Society of Surgical Oncology (ASTRO).

MATERIALS AND METHODS: A retrospective review including all cases of intra-operative ultrasound guided breast conserving surgery was performed at the National Cancer Institute Thailand between 2013 and 2016. Patient demographics, tumor variables, intraoperative frozen section and nal pathological margin outcomes were collected. Factors for positive or close margins were analyzed.

RESULTS: A total of 86 patients aged between 27 and 75 years with intra- operative ultrasound guided breast conserving surgery were included. Three cases (3.5%) of positive margin were detected by intra-operative frozen section and 4 cases (4.7%) by final pathology reports. There were 18 cases (20.9%) with a close margin (<1 mm). Factors affecting this result comprised multi-foci, presence of invasive ductal carcinoma (IDC) combined with ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC).

CONCLUSIONS: With the current SSO/ASTRO for adequate margin guidelines, using intra-operative ultrasound to locate the boundary for resection with breast conserving surgery provided a high success rate in obtaining final pathology free margin outcomes and minimizing re-operation risks especially when combined with intra-operative frozen section assessment. The chance of finding positive or close margins appears higher in cases of IDC combined with DCIS, ILC and with multi-foci cancers.}, } @article {pmid27796081, year = {2017}, author = {Lee, YJ and Kim, SH and Kang, BJ and Kang, YJ and Yoo, H and Yoo, J and Lee, J and Son, YH and Grimm, R}, title = {Intravoxel incoherent motion (IVIM)-derived parameters in diffusion-weighted MRI: Associations with prognostic factors in invasive ductal carcinoma.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {45}, number = {5}, pages = {1394-1406}, doi = {10.1002/jmri.25514}, pmid = {27796081}, issn = {1522-2586}, mesh = {Adult ; Aged ; Biopsy ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Middle Aged ; Motion ; Perfusion ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate relationships between intravoxel incoherent motion (IVIM) metrics of invasive ductal carcinoma of the breast and prognostic factors.

MATERIALS AND METHODS: This retrospective study included a total of 82 masses from 72 patients who underwent 3T breast magnetic resonance imaging (MRI) and diffusion-weighted imaging. IVIM metrics of tissue diffusivity (Dslow), pseudodiffusivity (Dfast), and perfusion fraction (Dpf) were measured using histogram analysis for whole lesion volumes. We evaluated relationships between IVIM metrics and prognostic factors or subtypes of invasive ductal carcinoma.

RESULTS: The Dslow 50[th] , 75[th] , and 90[th] percentile metrics were reduced in the estrogen receptor (ER)-positive group compared with the ER-negative group (individually, P = 0.044, 0.024, 0.045). Additionally, the Dslow 75[th] percentile value was a significant differentiator of histologic grade, tumor subtype, and Ki-67 grouping (individually, P = 0.024, 0.049, 0.016). The Dpf mean, 75[th] , 90[th] percentile, skewness, and kurtosis metrics were correlated with the size of ductal carcinoma in situ (DCIS) component (individually, P = 0.034, 0.032, 0.027, 0.013, 0.013).

CONCLUSION: The Dslow metrics differentiated between ER-positive and -negative groups, and the Dpf metrics were associated with the size of the DCIS component.

LEVEL OF EVIDENCE: 4 J. MAGN. RESON. IMAGING 2017;45:1394-1406.}, } @article {pmid27496539, year = {2016}, author = {Ben-David, BM and Avivi-Reich, M and Schneider, BA}, title = {Does the degree of linguistic experience (native versus nonnative) modulate the degree to which listeners can benefit from a delay between the onset of the maskers and the onset of the target speech?.}, journal = {Hearing research}, volume = {341}, number = {}, pages = {9-18}, doi = {10.1016/j.heares.2016.07.016}, pmid = {27496539}, issn = {1878-5891}, support = {STP-53875//CIHR/Canada ; MGC-42665//CIHR/Canada ; MOP-15359//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Auditory Perception ; Auditory Threshold ; Female ; Humans ; *Language ; Linguistics ; Male ; Noise ; *Perceptual Masking ; Psychometrics ; Reproducibility of Results ; Speech ; *Speech Intelligibility ; *Speech Perception ; Speech Reception Threshold Test ; Time Factors ; Young Adult ; }, abstract = {Background noise has a greater adverse effect on word recognition when people are listening in their second language (L2) as opposed to their first language (L1). The present study investigates the extent to which linguistic experience affects the ability of L2 listeners to benefit from a delay between the onset of a masker and the onset of a word. In a previous study (Ben-David, Tse & Schneider, 2012), word recognition thresholds for young L1s were found to improve with the increase in the delay between the onset of a masker (either a stationary noise or a babble of voices) and the onset of a word. The investigators interpreted this result as reflecting the ability of L1 listeners to rapidly segregate the target words from a masker. Given stream segregation depends, in part, on top-down knowledge-driven processes, we might expect stream segregation to be more "sluggish" for L2 listeners than for L1 listeners, especially when the masker consists of a babble of L2 voices. In the present study, we compared the ability of native English speakers to those who had either recent or long-term immersion in English as L2, to benefit from a delay between masker onset and word onset for English words. Results show that thresholds were higher for the two L2s groups than for the L1s. However, the rate at which word recognition improved with word-onset delay was unaffected by linguistic status, both when words were presented in noise, and in babble. Hence, for young listeners, stream segregation appears to be independent of linguistic status, suggesting that bottom-up sensory mechanisms play a large role in stream segregation in this paradigm. The implications of a failure of older L1 listeners (in Ben-David et al.) to benefit from a word-onset delay when the masker is a babble of voices are discussed.}, } @article {pmid27790442, year = {2016}, author = {Ishitha, G and Manipadam, MT and Backianathan, S and Chacko, RT and Abraham, DT and Jacob, PM}, title = {Clinicopathological Study of Triple Negative Breast Cancers.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {10}, number = {9}, pages = {EC05-EC09}, pmid = {27790442}, issn = {2249-782X}, abstract = {INTRODUCTION: Triple Negative Breast Cancers (TNBC) are a subset of breast cancers which are composed of different molecular subtypes. The most common is the basal like subtype, which has an adverse prognosis and limited treatment options.

AIM: This study was undertaken to assess the clinico-pathologic and immunohistochemical subtypes of triple negative breast cancers and assess how each of these subtypes correlate with clinical behaviour and survival outcomes.

MATERIALS AND METHODS: Fifty-three (22.2%) of 238 cases of primary invasive breast carcinomas diagnosed from January 2010 to June 2011 were found to be negative for immunohistochemical markers- ER, PR and HER2. These fifty three cases were included in the study and were classified into four histological subtypes proposed by Ishikawa et al. Basal markers- CK5/6, EGFR and CK14 were done on these cases and they were further classified immunohistochemically into basal and non basal subtypes. The morphological features, disease free survival and overall survival were evaluated for both basal and non basal subtypes.

RESULTS: Majority (96%) of TNBC cases were classified according to WHO as invasive ductal carcinoma (NOS). Type C Ishikawa histological subtype was found to be the commonest subtype in both basal and non-basal TNBC. Of 53 TNBC cases, basal immunohistochemical markers were performed on 47 cases only because of paucity of tissue. Of these 47 cases, thirty-five (74.4%) were found to be of basal like subtype and all these cases were picked up by a combination of CK5/6 and EGFR.

CONCLUSION: High grade morphological features, hormonal markers with additional use of basal markers can help identify the basal like subtype of TNBC, thereby predicting breast cancer survival. The combination of CK5/6 and EGFR identified all cases of basal subtype. EGFR in addition also has potential therapeutic implications. The morphological features and survival outcomes were not significantly different between basal and non-basal phenotypes.}, } @article {pmid27646773, year = {2017}, author = {Shao, G and Fan, L and Zhang, J and Dai, G and Xie, T}, title = {Association of DW/DCE-MRI features with prognostic factors in breast cancer.}, journal = {The International journal of biological markers}, volume = {32}, number = {1}, pages = {e118-e125}, doi = {10.5301/jbm.5000230}, pmid = {27646773}, issn = {1724-6008}, mesh = {Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging ; Carcinoma, Lobular/*diagnosis/diagnostic imaging ; Contrast Media/chemistry ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Follow-Up Studies ; Humans ; Image Interpretation, Computer-Assisted ; Middle Aged ; Neoplasm Staging ; Prognosis ; }, abstract = {BACKGROUND: Through analyzing apparent diffusion coefficient (ADC) values and morphological evaluations, this research aimed to study how magnetic resonance imaging (MRI)-based breast lesion characteristics can enhance the diagnosis and prognosis of breast cancer.

METHODS:: A total of 118 breast lesions, including 50 benign and 68 malignant lesions, from 106 patients were analyzed. All lesions were measured with both diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI. The average ADC of breast lesions was analyzed at b values of 600, 800 and 1,000 s/mm2. Lesion margins, lesion enhancement patterns, and dynamic curves were also investigated. The relations between MRI-based features and molecular prognostic factors were evaluated using Spearman's rank correlation analysis.

RESULTS:: A b value of 800 s/mm2 was used to distinguish malignant from benign breast lesions, with an ADC cutoff value of 1.365 × 10-3 mm2/s. The average ADC value between invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) was significantly different. Malignant lesions were more likely to have spiculated margins, heterogeneous enhancement and washout curves. On the other hand, DCIS was more likely to have spiculated margins, heterogeneous/rim enhancement and plateau/washout dynamic curves. A significant negative correlation was found between progesterone receptor (PR) status and dynamic imaging (p = 0.027), while a significant positive correlation was found between Ki-67 status and lesion enhancement (p = 0.045).

CONCLUSIONS:: Both ADC values and MRI morphological assessment could be used to distinguish malignant breast lesions from benign ones.}, } @article {pmid27786559, year = {2017}, author = {Lewin, AA and Heller, SL and Jaglan, S and Elias, K and Newburg, A and Melsaether, A and Moy, L}, title = {Radiologic-Pathologic Discordance and Outcome After MRI-Guided Vacuum-Assisted Biopsy.}, journal = {AJR. American journal of roentgenology}, volume = {208}, number = {1}, pages = {W17-W22}, doi = {10.2214/AJR.16.16404}, pmid = {27786559}, issn = {1546-3141}, mesh = {Adult ; Aged ; Biopsy, Needle/*statistics & numerical data ; Breast Neoplasms/*diagnostic imaging/epidemiology/*pathology ; False Negative Reactions ; Female ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging, Interventional/*statistics & numerical data ; Male ; Mammography/statistics & numerical data ; Middle Aged ; New York/epidemiology ; Prevalence ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The purpose of this study was to determine the rate, characteristics, and outcomes of discordant MRI-guided vacuum-assisted biopsy (VAB) in women with suspected breast cancer.

MATERIALS AND METHODS: This retrospective study reviewed 1314 MRI-guided VABs performed in 1211 women between 2007 and 2013 and yielded 25 discordant results in 24 women. MRI characteristics; BI-RADS assessments; whether the lesion was missed, partially sampled, or excised at biopsy; and biopsy and surgical pathology results were reviewed. Statistical analyses were performed using Fisher exact and Mann-Whitney U tests.

RESULTS: Among 1314 lesions that underwent MRI-guided VAB, 25 results were discordant (1.9%; 95% CI, 1.2-2.8%), and nine lesions with discordant results (36.0%, 95% CI, 18.5-56.9%) were malignant at surgical excision (three invasive ductal carcinoma and six ductal carcinoma in situ). There was no significant association between malignancy and lesion type, size, enhancement pattern, BI-RADS assessment, or clinical indication. Forty-four percent (11/25) of discordant lesions were missed, 48.0% (12/25) were partially sampled, and 8.0% (2/25) appeared to have been excised. Of the nine malignant lesions, 44.4% (4/9) discordant malignant lesions were missed, 44.4% (4/9) were partially sampled, and 11.1% (1/9) appeared to have been excised. Lesion sizes and types were similar in the missed and partially excised groups.

CONCLUSION: The potential for false-negative results at MRI-guided VAB underscores the importance of radiologic-histologic correlation and imaging review after biopsy. Rebiopsy or excision in discordant cases is therefore recommended.}, } @article {pmid27785066, year = {2016}, author = {Meng, L and Xu, Y and Xu, C and Zhang, W}, title = {Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation.}, journal = {OncoTargets and therapy}, volume = {9}, number = {}, pages = {6177-6185}, pmid = {27785066}, issn = {1178-6930}, abstract = {PURPOSE: Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery.

METHODS: Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis.

RESULTS: We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS.

CONCLUSION: Using novel gene expression profiling together with a meta-analysis validation approach, we have identified a three-gene signature with independent prognostic impact. Furthermore, CLDN11 may offer a biomarker to predict prognosis as well as a new target for prognostic and therapeutic intervention for human breast IDC.}, } @article {pmid27784457, year = {2016}, author = {Xiong, Y and Si, JW and Li, D and Wang, Y and Qu, LL and Zhang, H and Zhang, B and Li, T}, title = {[Clinical significance of expression of PI3Kp110α in breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {38}, number = {10}, pages = {743-749}, doi = {10.3760/cma.j.issn.0253-3766.2016.10.006}, pmid = {27784457}, issn = {0253-3766}, mesh = {Breast/enzymology ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/*metabolism ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinase/*metabolism ; Prognosis ; Receptor, ErbB-2/metabolism ; }, abstract = {Objective: To study the clinical significance of PI3Kp110α expression in breast cancer. Methods: The expressions of PI3Kp110α, HER2, PTEN, p-Akt and Ki-67 in invasive ductal carcinoma (IDC), adjacent ductal carcinoma in situ (DCIS) and normal breast tissue were detected by immunohistochemistry in 102 cases of breast cancer. The expression of PI3Kp110α in IDC was compared with those in DCIS and normal breast tissues. Correlations between expression of PI3Kp110α and expression of HER2, PTEN, p-Akt and Ki-67 index in IDC were analyzed. Correlation between expression of PI3Kp110α and stage of IDC was studied as well. Results: In the normal breast tissues, there were 97 cases (95.1%) with low level and 5 cases (4.9%) with high level expression of PI3Kp110α. In the DCIS tissues, there were 67 cases (65.7%) with low level and 35 cases (34.3%) with high level expression of PI3Kp110α. In the IDC tissues, there were 14 cases (13.7%) with low level and 88 cases (86.3%) with high level expression of PI3Kp110α. The difference between expression of PI3Kp110α in normal breast tissue, DCIS and IDC was significant (P<0.001). In the IDC tissues, expression of PI3Kp110α was negatively correlated with expression of HER2 (rs=-0.213, P=0.032) and PTEN (rs=-0.197, P=0.047), while was not significantly correlated with expression of p-Akt (P=0.119) and Ki-67 index (P=0.636). In contrast, expressions of HER-2 and p-Akt were positively correlated with Ki-67 index (P=0.001, P=0.035), while expression of HER2 was not correlated with p-Akt (P=0.177). Expression of PI3Kp110α was negatively correlated with T stage and TNM stage (P=0.003, P=0.016), while not correlated with N stage and M stage(both P>0.05). Expression of HER-2 was positively correlated with T stage (P=0.037), while not correlated with N stage, M stage and TNM stage (P>0.05 for all). Neither Ki-67 index nor expression of PTEN and p-Akt (P=0.194) were correlated with T stage, N stage, M stage and TNM stage. Conclusions: Expression of PI3Kp110α plays an important role in oncogenesis and development of breast cancer. Based on the fact that expression of PI3Kp110α is negatively correlated with expression of HER2 and PTEN and with T stage and TNM stage, we may conclude that increased expression of PI3Kp110α is another independent pathway in breast cancer development, and breast cancer patients with high expression of PI3Kp110α may have a better prognosis.}, } @article {pmid27010553, year = {2016}, author = {Brunstein Klomek, A and Snir, A and Apter, A and Carli, V and Wasserman, C and Hadlaczky, G and Hoven, CW and Sarchiapone, M and Balazs, J and Bobes, J and Brunner, R and Corcoran, P and Cosman, D and Haring, C and Kahn, JP and Kaess, M and Postuvan, V and Sisask, M and Tubiana, A and Varnik, A and Žiberna, J and Wasserman, D}, title = {Association between victimization by bullying and direct self injurious behavior among adolescence in Europe: a ten-country study.}, journal = {European child & adolescent psychiatry}, volume = {25}, number = {11}, pages = {1183-1193}, pmid = {27010553}, issn = {1435-165X}, mesh = {Adolescent ; *Adolescent Behavior ; Bullying/*statistics & numerical data ; Crime Victims/*statistics & numerical data ; Europe ; Female ; Humans ; Male ; Self-Injurious Behavior/*epidemiology ; }, abstract = {Previous studies have examined the association between victimization by bullying and both suicide ideation and suicide attempts. The current study examined the association between victimization by bullying and direct-self-injurious behavior (D-SIB) among a large representative sample of male and female adolescents in Europe. This study is part of the Saving and Empowering Young Lives in Europe (SEYLE) study and includes 168 schools, with 11,110 students (mean age = 14.9, SD = 0.89). Students were administered a self-report survey within the classroom, in which they were asked about three types of victimization by bullying (physical, verbal and relational) as well as direct self-injurious behavior (D-SIB). Additional risk factors (symptoms of depression and anxiety, suicide ideation, suicide attempts, loneliness, alcohol consumption, drug consumption), and protective factors (parent support, peer support, pro-social behavior) were included. The three types of victimization examined were associated with D-SIB. Examination of gender as moderator of the association between victimization (relational, verbal, and physical) and D-SIB yielded no significant results. As for the risk factors, depression, but not anxiety, partially mediated the effect of relational victimization and verbal victimization on D-SIB. As for the protective factors, students with parent and peer support and those with pro-social behaviors were at significantly lower risk of engaging in D-SIB after being victimized compared to students without support/pro-social behaviors. This large-scale study has clearly demonstrated the cross-sectional association between specific types of victimization with self-injurious behavior among adolescents and what may be part of the risk and protective factors in this complex association.}, } @article {pmid27781130, year = {2016}, author = {Paiva, C and Garcia, J and Silva, C and Araújo, A and Araújo, A and Santos, MD}, title = {Single Jejunum Metastasis from Breast Cancer Arising Twelve Years after the Initial Treatment.}, journal = {Case reports in oncological medicine}, volume = {2016}, number = {}, pages = {8594652}, pmid = {27781130}, issn = {2090-6706}, abstract = {Metastatic involvement of gastrointestinal tract from breast cancer is a rare event. We report the case of a 61-year-old woman presenting with bowel obstruction, related to metastasis of a primary breast cancer she had 12 years earlier (a triple-negative invasive ductal carcinoma treated with surgery and chemotherapy). Bowel obstruction was caused by a 20-centimeter tumor in the jejunum, involving also the transverse colon. The patient underwent en bloc resection of tumor with jejunum and transverse bowel segment and received adjuvant chemotherapy with carboplatin and paclitaxel. Twenty months later, she was alive without disease recurrence.}, } @article {pmid27495939, year = {2016}, author = {Amichai-Hamburger, Y and Etgar, S}, title = {Intimacy and Smartphone Multitasking-A New Oxymoron?.}, journal = {Psychological reports}, volume = {119}, number = {3}, pages = {826-838}, doi = {10.1177/0033294116662658}, pmid = {27495939}, issn = {1558-691X}, mesh = {Adult ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Sexual Partners/*psychology ; Smartphone/*statistics & numerical data ; Young Adult ; }, abstract = {This study investigated the relationship between smartphone multitasking and romantic intimacy. Participants currently in a romantic relationship (N = 128; 98 women; M age = 26.7 years, SD = 4.3) filled out two sets of questionnaires: The Emotional Intimacy Scale, measuring romantic intimacy, and the mobile phone interference in life scale, measuring multitasking on a smartphone. Participants filled out each questionnaire twice, once in relation to themselves and once in relation to their partner (for the partner questionnaire, statements were altered from the first person to the third person singular, he/she instead of I). Results suggested that only the partners' smartphone multitasking scores were negatively related to ratings of romantic intimacy, whereas participants' own smartphone multitasking scores were not related to ratings of romantic intimacy. These results can be explained by the actor-observer asymmetry, suggesting that participants attributed their multitasking behaviors to situations, but attributed their partners multitasking behaviors to behavior patterns or intentionality. This research suggests that smartphone multitasking has a negative association with face-to-face interactions. People should attend to the costs of smartphone use during face-to-face interactions.}, } @article {pmid27776915, year = {2017}, author = {Mendler, M and Riedinger, C and Schlotterer, A and Volk, N and Fleming, T and Herzig, S and Nawroth, PP and Morcos, M}, title = {Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan.}, journal = {Journal of diabetes and its complications}, volume = {31}, number = {2}, pages = {304-310}, doi = {10.1016/j.jdiacomp.2016.09.014}, pmid = {27776915}, issn = {1873-460X}, mesh = {Animals ; Behavior, Animal ; Caenorhabditis elegans/enzymology/growth & development/*metabolism ; Caenorhabditis elegans Proteins/agonists/*antagonists & inhibitors/genetics/*metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Glucose/*poisoning ; Glycation End Products, Advanced/metabolism ; Lactoylglutathione Lyase/antagonists & inhibitors/genetics/*metabolism ; Longevity ; Mutation ; Neuroprotection ; Osmolar Concentration ; *Oxidative Stress ; Peptide Hormones/agonists/*antagonists & inhibitors/genetics/metabolism ; RNA Interference ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/antagonists & inhibitors/genetics/*metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied.

RESULTS: In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively.

CONCLUSIONS: Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4, thus giving further insight into the pathophysiology of diabetic complications.}, } @article {pmid27633896, year = {2016}, author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Gomulkiewicz, A and Witkiewicz, W and Dziegiel, P}, title = {Periostin expression in cancer-associated fibroblasts of invasive ductal breast carcinoma.}, journal = {Oncology reports}, volume = {36}, number = {5}, pages = {2745-2754}, doi = {10.3892/or.2016.5095}, pmid = {27633896}, issn = {1791-2431}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Cancer-Associated Fibroblasts/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating ; Cell Adhesion/genetics ; Cell Adhesion Molecules/*biosynthesis/genetics ; Cell Proliferation ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; }, abstract = {Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters. Material for immunohistochemical studies (IHC) comprise of 70 IDC cases, 44 DCIS cases and 21 cases of fibrocystic change (FC). Frozen (-80˚C) fragments of tumours taken from 41 patients with IDC were used for molecular studies (real-time PCR), including 11 cases of IDC subjected to laser capture microdissection (LCM). POSTN expression was shown mainly in tumour stromal cells, i.e. cancer-associated fibroblasts (CAFs). Statistically significant higher level of POSTN expression in CAFs in IDC as compared to FC (p<0.0001) was observed. Additionally, statistically elevated expression level of POSTN in CAFs in IDC relative to DCIS (p<0.0001) and significantly increased expression of POSTN in CAFs in DCIS in comparison to FC (p=0.0158) was also shown. High level of POSTN expression in CAFs in IDC (>8 IRS points) was significantly correlated with tumour malignancy grade (G) (p=0.0070). Moreover, higher POSTN expression by CAFs was associated with patient shorter overall survival. Significant increase of POSTN expression on mRNA and protein level in CAFs in IDC with the growing malignancy grade of the tumours (G) was shown. Furthermore, with the use of LCM method, statistically significant higher expression of mRNA POSTN in stromal cells relative to cancer cells (p<0.001) was noted. POSTN might be a factor playing an important role in the mechanism of IDC progression.}, } @article {pmid27260371, year = {2016}, author = {Lynch, G and Bell, K and Long, D and Burmeister, L}, title = {Factors associated with the successful removal of indwelling urinary catheters post-operatively in the fragility hip fracture patient.}, journal = {International journal of orthopaedic and trauma nursing}, volume = {23}, number = {}, pages = {25-31}, doi = {10.1016/j.ijotn.2016.02.006}, pmid = {27260371}, issn = {1878-1292}, mesh = {Aged ; Aged, 80 and over ; *Catheters, Indwelling ; Cohort Studies ; Device Removal ; Female ; Femoral Fractures/*nursing/surgery ; Fractures, Spontaneous/*nursing/surgery ; Health Services for the Aged ; Humans ; Male ; Postoperative Complications ; *Practice Patterns, Nurses' ; Retrospective Studies ; Treatment Outcome ; Urinary Incontinence/*prevention & control ; }, abstract = {INTRODUCTION: Patients presenting to hospital with a fragility hip fracture are routinely catheterized in the emergency department. Studies have found that the duration of catheterization is the greatest and most important risk factor for developing a urinary tract infection. Whilst there is a considerable body of evidence around correct techniques for insertion of urinary catheters, there appears to be little evidence as to the timing of their removal.

AIM OF THE STUDY: To describe the current practice of indwelling catheter (IDC) removal post operatively in the fragility hip fracture patient and to identify factors associated with the successful removal of IDCs post operatively in the same cohort of patients.

METHODS: This study was a retrospective cohort analysis of patients admitted to a large, tertiary hospital with an established ortho-geriatric model of care.

RESULTS: Aperient regime was the only factor that appeared to have a significant impact on the successful IDC removal. The patient commenced on the aperient regime was three times more likely to have an unsuccessful IDC removal than the patient on a limited or no aperient regime.

CONCLUSION: This study highlights the need for redesigning care that is patient focused, evidence-based, effective and efficient. The argument that a patient's bowel is required to be emptied prior to the successful removal of an IDC appears to be false, as in this study it was not identified as a predictor of successful IDC removal. A prospective clinical trial may be the next step forward in developing a clinical guideline for the successful removal of IDCs in the fragility hip fracture patient and/or surgical patient. Nurses have a crucial role to play in contributing to evidence-based practice and are continually challenged to do so.}, } @article {pmid27775181, year = {2017}, author = {Kaya, Z and Akkiprik, M and Karabulut, S and Peker, I and Gullu Amuran, G and Ozmen, T and Gulluoglu, BM and Kaya, H and Ozer, A}, title = {Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.}, journal = {Journal of clinical laboratory analysis}, volume = {31}, number = {5}, pages = {}, pmid = {27775181}, issn = {1098-2825}, mesh = {Breast/*chemistry ; Breast Neoplasms/chemistry/*epidemiology/*genetics/mortality ; Cohort Studies ; DNA Methylation ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/*genetics ; Middle Aged ; Survival Analysis ; Telomere/chemistry/*genetics ; Turkey ; }, abstract = {BACKGROUND: Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL.

METHODS: Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting.

RESULTS: Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters.

CONCLUSION: These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.}, } @article {pmid27770782, year = {2016}, author = {Derkaoui, T and Bakkach, J and Mansouri, M and Loudiyi, A and Fihri, M and Alaoui, FZ and Barakat, A and El Yemlahi, B and Bihri, H and Nourouti, NG and Mechita, MB}, title = {Triple negative breast cancer in North of Morocco: clinicopathologic and prognostic features.}, journal = {BMC women's health}, volume = {16}, number = {1}, pages = {68}, pmid = {27770782}, issn = {1472-6874}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Morocco ; *Prognosis ; Retrospective Studies ; Triple Negative Breast Neoplasms/*mortality/*physiopathology ; }, abstract = {BACKGROUND: Triple Negative Breast Cancer (TNBC) is defined by a lack of estrogen and progesterone receptor gene expression and by the absence of overexpression on HER2. It is associated to a poor prognosis. We propose to analyze the clinicopathologic and prognostic characteristics of this breast cancer subtype in a Mediterranean population originated or resident in the North of Morocco.

METHODS: We conducted a retrospective study of 279 patients diagnosed with breast cancer between January 2010 and January 2015. Clinicopathologic and prognostic features have been analyzed. Disease-Free Survival (DFS) and Overall Survival (OS) have been estimated.

RESULTS: Of all cases, forty-nine (17.6 %) were identified as having triple negative breast cancer with a median age of 46 years. The average tumor size was 3.6 cm. The majority of patients have had invasive ductal carcinoma (91.8 %) and 40.4 % of them were grade III SBR. Nodal metastasis was detected in 38.9 % of the patients and vascular invasion was found in 36.6 % of them. About half of the patients had an early disease (53.1 %) and 46.9 % were diagnosed at an advanced stage. Patients with operable tumors (61.2 %) underwent primary surgery and adjuvant chemotherapy. Patients with no operable tumors (26.5 %) received neoadjuvant chemotherapy followed by surgery, and patients with metastatic disease (12.2 %) were treated by palliative chemotherapy. DFS and OS at 5 years were respectively 83.7 and 71.4 %. Among 49, twelve had recurrences, found either when diagnosing them or after a follow-up. Local relapse was 6.1 %. Lung and liver metastases accounted consecutively for 8.2 and 10.2 %. Bone metastases were found in 4.1 % and brain metastases in 2.1 % of the cases.

CONCLUSION: Our results are in accordance with literature data, particularly what concerning young age and poor prognosis among TNBC phenotype. Therefore, the identification of BRCA mutations in our population seems to be essential in order to better adapt management options for this aggressive form of breast cancer.}, } @article {pmid27418334, year = {2016}, author = {Quecedo Gutiérrez, L and Ruiz Abascal, R and Calvo Vecino, JM and Peral García, AI and Matute González, E and Muñoz Alameda, LE and Guasch Arévalo, E and Gilsanz Rodríguez, F}, title = {"Do not do" recommendations of the Spanish Society of Anaesthesiology, Critical Care and Pain Therapy. "Commitment to Quality by Scientific Societies" Project.}, journal = {Revista espanola de anestesiologia y reanimacion}, volume = {63}, number = {9}, pages = {519-527}, doi = {10.1016/j.redar.2016.05.002}, pmid = {27418334}, issn = {2340-3284}, mesh = {*Anesthesiology ; *Critical Care ; Humans ; Pain ; Practice Guidelines as Topic ; Quality of Health Care ; *Societies, Scientific ; Spain ; }, abstract = {In April 2013 the Ministry of Health (MSSSI) adopted the project called "Commitment to Quality by Scientific Societies in Spain", in response to social and professional demands for sustainability of the health system. The initiative is part of the activities of the Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System, and is coordinated jointly by the Quality and Cohesion Department, the Aragon Institute of Health Sciences (IACS), and the Spanish Society of Internal Medicine (SEMI). All the scientific societies in Spain have been included in this project, and its main objective is to reduce the unnecessary use of health interventions in order to agree "do not do" recommendations, based on scientific evidence. The primary objective was to identify interventions that have not proven effective, have limited or doubtful effectiveness, are not cost-effective, or do not have priority. Secondary objectives were: reducing variability in clinical practice, to spread information between doctors and patients to guide decision-making, the appropriate use of health resources and, the promotion of clinical safety and reducing iatrogenesis. The selection process of the 5 "do not do" recommendations was made by Delphi methodology. A total of 25 panellists (all anaesthesiologists) chose between 15 proposals based on: evidence that supports quality, relevance, or clinical impact, and the people they affect. The 5 recommendations proposed were: Do not maintain deep levels of sedation in critically ill patients without a specific indication; Do not perform preoperative chest radiography in patients under 40 years-old with ASA physical status I or II; Do not systematically perform preoperative tests in cataract surgery unless otherwise indicated based on clinical history and physical examination; Do not perform elective surgery in patients with anaemia at risk of bleeding until a diagnostic workup is performed and treatment is given; and not perform laboratory tests (blood count, biochemistry and coagulation) prior to surgery in healthy or low risk patients (ASA I and II) with minimal estimated blood loss.}, } @article {pmid27406466, year = {2016}, author = {El-Hage, A and Ruel, C and Afif, W and Wissanji, H and Hogue, JC and Desbiens, C and Leblanc, G and Poirier, É}, title = {Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.}, journal = {Journal of surgical oncology}, volume = {114}, number = {5}, pages = {543-547}, doi = {10.1002/jso.24362}, pmid = {27406466}, issn = {1096-9098}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Canada ; Carcinoma, Lobular/epidemiology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms/epidemiology/*secondary ; }, abstract = {BACKGROUND AND OBJECTIVES: Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases.

METHODS: Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded.

RESULTS: Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC.

CONCLUSION: Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27393599, year = {2016}, author = {Mateo, AM and Pezzi, TA and Sundermeyer, M and Kelley, CA and Klimberg, VS and Pezzi, CM}, title = {Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.}, journal = {Journal of surgical oncology}, volume = {114}, number = {5}, pages = {533-536}, doi = {10.1002/jso.24367}, pmid = {27393599}, issn = {1096-9098}, mesh = {Aged ; Breast Neoplasms/*mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Carcinoma, Medullary/*mortality/*pathology/therapy ; Databases, Factual ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Survival Rate ; United States/epidemiology ; }, abstract = {BACKGROUNDS AND OBJECTIVES: Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB).

METHODS: Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference.

RESULTS: Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46).

CONCLUSIONS: There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27760942, year = {2016}, author = {Matsuoka, A and Hirano, A and Hattori, A and Ogura, K and Inoue, H and Yukawa, H and Sakaguchi, S and Tanaka, N and Kodera, A and Kamimura, M and Naritaka, Y and Shimizu, T}, title = {[Ethinylestradiol Following Everolimus plus Exemestane Was Effective in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer - A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {10}, pages = {1219-1222}, pmid = {27760942}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Estrogen Replacement Therapy ; Ethinyl Estradiol/administration & dosage ; Everolimus/administration & dosage ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Mastectomy ; Postmenopause ; }, abstract = {A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin.Then, estrogen therapy with ethinylestradiol(EE2)was started in December 2013.T he pleural effusion disappeared and the liver metastases were reduced.After 11 months of progression-free survival(PFS), regrowth of the liver metastases was seen.Thus, everolimus plus exemestane was administered, and approximately 8 months of PFS was obtained.Therefore, both EE2 and everolimus are effective therapy even for heavily pretreated metastatic breast cancer.}, } @article {pmid27760180, year = {2016}, author = {Fu, J and Wu, L and Jiang, M and Li, D and Jiang, T and Hong, Z and Wang, F and Li, S}, title = {Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer.}, journal = {PloS one}, volume = {11}, number = {10}, pages = {e0164921}, pmid = {27760180}, issn = {1932-6203}, mesh = {Adenocarcinoma, Mucinous/*epidemiology/metabolism/mortality ; Aged ; Analysis of Variance ; Breast Neoplasms/*epidemiology/metabolism/mortality ; Carcinoma, Ductal, Breast/*epidemiology/metabolism/mortality ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptors, Estrogen/*metabolism ; Risk Factors ; SEER Program ; Survival Analysis ; }, abstract = {BACKGROUND: The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC.

RESULTS: There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001).

CONCLUSIONS: Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk regression model, as a more rational model, is recommended for use in the survival analysis of patients with MBC in the future.}, } @article {pmid27219913, year = {2016}, author = {Santangelo, G and Sacco, R and Siciliano, M and Bisecco, A and Muzzo, G and Docimo, R and De Stefano, M and Bonavita, S and Lavorgna, L and Tedeschi, G and Trojano, L and Gallo, A}, title = {Anxiety in Multiple Sclerosis: psychometric properties of the State-Trait Anxiety Inventory.}, journal = {Acta neurologica Scandinavica}, volume = {134}, number = {6}, pages = {458-466}, doi = {10.1111/ane.12564}, pmid = {27219913}, issn = {1600-0404}, mesh = {Adult ; Anxiety/epidemiology/etiology/*psychology ; Depression/epidemiology/etiology/psychology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/*psychology ; *Neuropsychological Tests ; Prevalence ; *Psychiatric Status Rating Scales ; Psychometrics ; Reference Values ; Sex Characteristics ; }, abstract = {OBJECTIVE: The aims of the present study were to examine psychometric properties of the Spielberger State-Trait Anxiety Inventory (STAI-Y-1 and STAI-Y-2, respectively) in a Multiple Sclerosis (MS) population and to identify a cut-off score to detect those MS patients with high level of state and/or trait anxiety who could be more vulnerable to development of depression and/or cognitive defects.

MATERIAL AND METHODS: The STAI-Y-1 and STAI-Y-2 was completed by a group of patients (n = 175) affected by MS and a group of healthy subjects (n = 150) matched for age, educational level, and gender. In MS patients internal consistency, divergent and discriminant validities were evaluated. Construct validity was examined by exploratory factor analysis for each scale.

RESULTS: There was no missing data, no floor or ceiling effects for both scales. The two scales showed high internal consistency, good divergent, and Known-groups validities. To identify high levels of state and trait anxiety in a patient with MS, we proposed three gender specific screening cut-off values (1, 1.5, 2 SD) for the STAI-Y-1 and the STAI-Y-2.

CONCLUSIONS: The findings showed that the STAI-Y-1 and the STAI-Y-2 are a valid tool for clinical use in MS patients and can be useful to measure the severity of anxiety and to identify those patients with high anxiety to introduce them in specific non-pharmacological intervention.}, } @article {pmid27755404, year = {2017}, author = {Sakamoto, Y and Fujita, S and Adachi, M and Sakamoto, H and Naruse, T and Yanamoto, S and Ikeda, T and Umeda, M}, title = {Carcinoma Ex Pleomorphic Adenoma of the Tongue: Difficulty in Diagnosis Between Metastasis of Breast Cancer and Salivary Tumor.}, journal = {The Journal of craniofacial surgery}, volume = {28}, number = {2}, pages = {e182-e185}, doi = {10.1097/SCS.0000000000003136}, pmid = {27755404}, issn = {1536-3732}, mesh = {Adenocarcinoma/*diagnosis/etiology/pathology ; Adenoma, Pleomorphic/complications/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Diagnosis, Differential ; Female ; Glossectomy ; Humans ; Middle Aged ; Neoplasms, Second Primary/*diagnosis/etiology/pathology ; Salivary Gland Neoplasms/complications/*pathology ; Tongue Neoplasms/*diagnosis/etiology/pathology ; }, abstract = {Carcinoma ex pleomorphic adenoma (CEPA) is a carcinoma that shows histologic evidence of arising in or from a benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma often occurs in parotid glands, but is extremely rarely in the tongue. A 53-year-old Japanese woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Hospital, because of tumor of the right dorsum tongue. She had a history of surgery of breast cancer (invasive ductal carcinoma) and it was disseminated to the lung and bone. Macroscopic examination revealed an oval tumor with a smooth mucosal surface of 10 mm in diameter in the right dorsum tongue. A clinical diagnosis was metastasis from breast cancer or primary salivary gland tumor. Histologic diagnosis of the biopsy specimen was CEPA. She underwent partial glossectomy under general anesthesia. The final diagnosis of surgical materials was CEPA based on the differential diagnosis from breast carcinoma. She is alive bearing disseminated breast carcinoma without recurrence of CEPA at 6 months after glossectomy.}, } @article {pmid27435448, year = {2016}, author = {Erro, R and Picillo, M and Vitale, C and Amboni, M and Moccia, M and Santangelo, G and Pellecchia, MT and Barone, P}, title = {The non-motor side of the honeymoon period of Parkinson's disease and its relationship with quality of life: a 4-year longitudinal study.}, journal = {European journal of neurology}, volume = {23}, number = {11}, pages = {1673-1679}, doi = {10.1111/ene.13106}, pmid = {27435448}, issn = {1468-1331}, mesh = {Disease Progression ; Dopamine Agonists/therapeutic use ; Female ; Humans ; Levodopa/therapeutic use ; Longitudinal Studies ; Male ; Parkinson Disease/*diagnosis/drug therapy ; *Quality of Life ; Severity of Illness Index ; Sex Factors ; Symptom Assessment ; }, abstract = {BACKGROUND AND PURPOSE: Very little is known about the progression of non-motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of de-novo, previously untreated, patients with PD.

METHODS: Consecutive de-novo (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non-motor features as well as of quality of life measures.

RESULTS: Sixty-one patients were prospectively followed-up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa-equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life.

CONCLUSIONS: Non-motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non-dopaminergic networks and consider NMSs in their outcomes.}, } @article {pmid27737658, year = {2016}, author = {Sulaj, A and Zemva, J and Zech, U and Woehning, A and Brune, M and Rudofsky, G and Nawroth, PP and Fleming, T and von Bauer, R}, title = {The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule.}, journal = {BMC endocrine disorders}, volume = {16}, number = {1}, pages = {56}, pmid = {27737658}, issn = {1472-6823}, mesh = {Adiponectin/blood ; Adult ; Age Factors ; Antigens, CD/*blood ; Biomarkers/blood ; Blood Glucose ; Body Weight Maintenance ; C-Reactive Protein/metabolism ; Cell Adhesion Molecules, Neuronal/*blood ; Cholesterol/blood ; Female ; Fetal Proteins/*blood ; Glucose Tolerance Test ; Homeostasis ; Humans ; Insulin/blood ; Insulin Resistance ; Leptin/blood ; Male ; Multivariate Analysis ; Obesity/blood/*metabolism ; *Risk Reduction Behavior ; Triglycerides/blood ; Weight Loss ; }, abstract = {BACKGROUND: The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters.

METHODS: Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated.

RESULTS: At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline.

CONCLUSIONS: sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.}, } @article {pmid27737482, year = {2016}, author = {Keränen, AK and Haapea, M and Rissanen, T}, title = {Ultrasonography as a Guiding Method in Breast Micro-Calcification Vacuum-Assisted Biopsies.}, journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)}, volume = {37}, number = {5}, pages = {497-502}, doi = {10.1055/s-0041-107998}, pmid = {27737482}, issn = {1438-8782}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle/*methods ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/*pathology ; Calcinosis/*diagnostic imaging/*pathology ; Diagnosis, Differential ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Image-Guided Biopsy/*methods ; Middle Aged ; Retrospective Studies ; Stereotaxic Techniques ; Ultrasonography, Interventional/*methods ; Ultrasonography, Mammary/*methods ; Vacuum ; Young Adult ; }, abstract = {Purpose: To assess the visibility of breast micro-calcifications using ultrasonography (US) and the accuracy and clinical usefulness of vacuum-assisted biopsy (VAB) using US guidance (USVAB) as compared to stereotactic guidance (SVAB). Materials and Methods: The study material comprised 158 retrospectively reviewed micro-calcification cases examined with US before VAB. The pre-biopsy US positivity frequency distributions were calculated, and the sensitivity, specificity and accuracy of VAB determined by comparing VAB histology with the surgical pathology or a 12-month follow-up. Results: 158 US examinations yielded 80 positive and 78 negative results. US positivity correlated to a large size and a suspicious BI-RADS category of the calcifications. USVAB was performed in 49 cases with 61 % malignant, 12 % high-risk and 27 % benign results. The percentages for the 109 SVAB cases were 40 %, 28 % and 32 %, respectively. Specimen radiography demonstrated calcifications in 48 of the 49 (98 %) USVAB cases and in 107 of the 109 (98 %) SVAB cases. The overall accuracy of VAB was 94 % (USVAB 98 %, SVAB 94 %), the sensitivity was 88 % (USVAB 97 %, SVAB 83 %), and the specificity was 100 %. The higher sensitivity of USVAB was due to an accumulation of atypical hyperplasia diagnoses in the SVAB group. The final diagnosis was invasive ductal carcinoma in 21 US-positive and in 4 US-negative cases. Conclusion: Approximately 50 % of mammographically detected micro-calcifications could be detected with ultrasonography. US was found to be a valuable alternative guidance method for vacuum-assisted biopsy of micro-calcifications with a technical success rate and diagnostic accuracy well comparable to the stereotactic method.}, } @article {pmid27727404, year = {2016}, author = {Gabanti, E and Bruno, F and Scaramuzzi, L and Mangione, F and Zelini, P and Gerna, G and Lilleri, D}, title = {Predictive value of human cytomegalovirus (HCMV) T-cell response in the control of HCMV infection by seropositive solid-organ transplant recipients according to different assays and stimuli.}, journal = {The new microbiologica}, volume = {39}, number = {4}, pages = {247-258}, pmid = {27727404}, issn = {1121-7138}, mesh = {Adult ; Aged ; Antigens, Viral ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cytomegalovirus Infections/*immunology/*prevention & control ; Enzyme-Linked Immunospot Assay ; Female ; Humans ; Male ; Middle Aged ; Organ Transplantation/*adverse effects ; Predictive Value of Tests ; T-Lymphocytes/*physiology ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV) is still the most common viral infection in solid-organ transplant recipients (SOTR). Our study aimed to identify the predictive values of the T-cell response able to protect from HCMV disease, according to different assays. Viral DNA was determined by real-time PCR. The T-cell immune response to HCMV infection was investigated in SOTR according to the following assays and stimuli: cytokine flow cytometry (CFC) after peripheral blood mononuclear cell (PBMC) stimulation with autologous HCMV-infected dendritic cells (iDC) vs three ELISPOT assays using PBMCs stimulated with: 1. HCMV-infected cell lysate (iCL); 2. a pool of 34 epitopic peptides (PP) from different HCMV proteins; 3. a commercial pp65 peptide pool (CPM). ELISPOT results were normalized to T-cell counts. Overall, 51 SOTR were enrolled: 29 (57%) had low viral load (LVL) self-resolving infections, 19 (37%) high viral load (HVL) infections treated with antiviral drugs, and 3 (6%) tissue-invasive disease (TID). At DNAemia peak, ROC analysis showed that CFC-iDC CD4+ and the ELISPOT-iCL assays yielded overlapping area under the curve (AUC) results. The time needed to reconstitute protective T-cell immunity in SOTR with HVL infections was significantly longer with each assay compared to LVL infections. Using the CFC-iDC assay as a reference test (requiring 7 days to complete), the 24h ELISPOT-iCL assay provides similar results in terms of protection prediction from HCMV infection.}, } @article {pmid27721883, year = {2016}, author = {Ricciuti, B and Leonardi, GC and Ravaioli, N and De Giglio, A and Brambilla, M and Prosperi, E and Ribacchi, F and Meacci, M and Crinò, L and Maiettini, D and Chiari, R and Metro, G}, title = {Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.}, journal = {Journal of breast cancer}, volume = {19}, number = {3}, pages = {324-329}, pmid = {27721883}, issn = {1738-6756}, abstract = {Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.}, } @article {pmid27721881, year = {2016}, author = {Park, CJ and Kim, EK and Moon, HJ and Yoon, JH and Kim, MJ}, title = {Reliability of Breast Ultrasound BI-RADS Final Assessment in Mammographically Negative Patients with Nipple Discharge and Radiologic Predictors of Malignancy.}, journal = {Journal of breast cancer}, volume = {19}, number = {3}, pages = {308-315}, pmid = {27721881}, issn = {1738-6756}, abstract = {PURPOSE: The purpose of this study was to retrospectively investigate the reliability of breast ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) final assessment in mammographically negative patients with pathologic nipple discharge, and to determine the clinical and ultrasonographic variables associated with malignancy in this group of patients.

METHODS: A total of 65 patients with 67 mammographically negative breast lesions that were pathologically confirmed through US-guided biopsy were included.

RESULTS: Of the 53 BI-RADS category 4 and 5 lesions, eight (15.1%) were malignant (six ductal carcinomas in situ, one invasive ductal carcinoma, and one solid papillary carcinoma). There was no malignancy among the remaining 14 category 3 lesions. Malignant lesions more frequently displayed a round or irregular shape (75.0%, 6/8; p=0.030) and nonparallel orientation (33.3%, 4/12; p=0.029) compared to the benign lesions. The increase in the BI-RADS category corresponded with a rise in the malignancy rate (p=0.004).

CONCLUSION: The BI-RADS lexicon and final assessment of breast US reliably detect and characterize malignancy in mammographically negative patients with pathologic nipple discharge.}, } @article {pmid27721880, year = {2016}, author = {Nam, SY and Ko, EY and Han, BK and Shin, JH and Ko, ES and Hahn, SY}, title = {Breast Imaging Reporting and Data System Category 3 Lesions Detected on Whole-Breast Screening Ultrasound.}, journal = {Journal of breast cancer}, volume = {19}, number = {3}, pages = {301-307}, pmid = {27721880}, issn = {1738-6756}, abstract = {PURPOSE: This study assessed the incidence and cancer rate of probably benign lesions detected on bilateral whole-breast screening ultrasound (US), which corresponded to US Breast Imaging Reporting and Data System (BI-RADS) category 3, and evaluated the proper management of those lesions.

METHODS: This study was approved by the Institutional Review Board in our institution, which waived informed patient consent. We retrospectively reviewed US images of 1,666 patients who underwent bilateral whole-breast screening US as a supplemental screening test to negative screening mammography or screening US only. The incidence, clinical course, and cancer rate of screening US-detected probably benign lesions corresponding to US BI-RADS category 3 were investigated, and the size and multiplicity of screening US-detected category 3 lesions were evaluated.

RESULTS: Probably benign lesions corresponding to US BI-RADS category 3 were detected in 689 of 1,666 patients (41.4%) who underwent screening US. Among them, 653 had follow-up US images for at least 24 months, and among these 653, 190 (29.1%) had multiple bilateral category 3 lesions. Moreover, 539 of 1,666 patients (32.4%) had lesions ≤1 cm in size and 114 of 1,666 (6.8%) had lesions >1 cm (median, 0.82 cm; range, 0.3-4.2 cm). Four of the 653 patients (0.6%) showed suspicious interval changes and were categorized into BI-RADS category 4. Biopsy analysis confirmed only one lesion as invasive ductal carcinoma at the 6-month follow-up; another lesion was an intraductal papilloma and the remaining two were fibroadenomas. Overall cancer rate of the screening US-detected BI-RADS category 3 lesions was 0.2%.

CONCLUSION: The incidence of category 3 lesions detected on screening US only was very high, but the cancer rate was very low. Therefore, in an average-risk population, routine screening US is preferable over short-term follow-up for BI-RADS category 3 lesions detected on whole-breast screening US.}, } @article {pmid27720394, year = {2016}, author = {Nogués, L and Reglero, C and Rivas, V and Salcedo, A and Lafarga, V and Neves, M and Ramos, P and Mendiola, M and Berjón, A and Stamatakis, K and Zhou, XZ and Lu, KP and Hardisson, D and Mayor, F and Penela, P}, title = {G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis.}, journal = {EBioMedicine}, volume = {13}, number = {}, pages = {132-145}, pmid = {27720394}, issn = {2352-3964}, support = {R01 CA167677/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Apoptosis/genetics ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Cell Transformation, Neoplastic/*metabolism ; Disease Models, Animal ; Female ; G-Protein-Coupled Receptor Kinase 2/genetics/*metabolism ; Gene Expression ; Histone Deacetylase 6 ; Histone Deacetylases/genetics/*metabolism ; Humans ; Mice, Transgenic ; Models, Biological ; NIMA-Interacting Peptidylprolyl Isomerase/*metabolism ; Prognosis ; RNA Interference ; RNA, Small Interfering/genetics ; *Signal Transduction ; Tumor Burden ; }, abstract = {In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1.}, } @article {pmid27718417, year = {2016}, author = {Wang, XL and Tao, L and Zhou, XL and Wei, H and Sun, JW}, title = {Initial experience of automated breast volume scanning (ABVS) and ultrasound elastography in predicting breast cancer subtypes and staging.}, journal = {Breast (Edinburgh, Scotland)}, volume = {30}, number = {}, pages = {130-135}, doi = {10.1016/j.breast.2016.09.012}, pmid = {27718417}, issn = {1532-3080}, mesh = {Adenocarcinoma/diagnostic imaging/pathology ; Adenocarcinoma, Mucinous/*diagnostic imaging/pathology ; Adult ; Aged ; Automation ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Carcinoma, Neuroendocrine/*diagnostic imaging/pathology ; Carcinoma, Papillary/*diagnostic imaging/pathology ; Elasticity Imaging Techniques ; Female ; Humans ; Imaging, Three-Dimensional ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVES: Breast cancer is a heterogeneous disease consisting of distinct histopathological subtypes with different clinical outcomes. In this article, we identified the automated breast volume scanning (ABVS) and shear wave velocity (SWV) characteristics of different pathological types of breast carcinoma.

METHODS: A retrospective review of both ABVS and SWV imaging of 118 consecutive breast masses was performed. The imaging features of both techniques were assessed with reference to histopathological results.

RESULTS: Echo heterogeneity with a smooth and lobulated margin was a significant feature more frequently found in mucinous carcinoma groups (100%, P < 0.05). Between different stages of ductal carcinoma, echo homogeneity was more likely in high-grade ductal carcinomas (P < 0.05). SWV differences existed between inside tumor areas and either tumor boundary or tissues outside the tumors (P < 0.05), and values differed between different breast carcinoma stages. The central and tumor margin areas of ductal carcinomas were much harder than in tubular carcinoma and micro-carcinoma, respectively (P < 0.05). SWV ROC curve analyses yielded a cut-off value of 3.015 m/s between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma in the central part of lesions, with 83.5% sensitivity and 80% specificity for T0 vs T1-3 staging.

CONCLUSIONS: Since some features were associated with different breast carcinoma types and stages, ABVS and SWV imaging has the potential to give clues about breast carcinoma differentiation in a non-invasive manner.}, } @article {pmid27718416, year = {2016}, author = {Fives, C and O'Neill, CJ and Murphy, R and Corrigan, MA and O'Sullivan, MJ and Feeley, L and Bennett, MW and O'Connell, F and Browne, TJ}, title = {When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.}, journal = {Breast (Edinburgh, Scotland)}, volume = {30}, number = {}, pages = {125-129}, doi = {10.1016/j.breast.2016.09.006}, pmid = {27718416}, issn = {1532-3080}, mesh = {Adult ; Aftercare ; Aged ; Biopsy, Large-Core Needle ; Breast Carcinoma In Situ/complications/diagnostic imaging/pathology/*therapy ; Breast Neoplasms/complications/diagnostic imaging/pathology/*therapy ; Cohort Studies ; Disease Management ; Female ; Fibroadenoma/complications/diagnostic imaging/pathology/*therapy ; Humans ; Hyperplasia ; Mammography ; *Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; *Watchful Waiting ; }, abstract = {BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up.

METHODS: A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded.

RESULTS: 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.}, } @article {pmid27718380, year = {2016}, author = {Tolmacz, R and Efrati, Y and Ben-David, BM}, title = {The sense of relational entitlement among adolescents toward their parents (SREap) - Testing an adaptation of the SRE.}, journal = {Journal of adolescence}, volume = {53}, number = {}, pages = {127-140}, doi = {10.1016/j.adolescence.2016.09.003}, pmid = {27718380}, issn = {1095-9254}, mesh = {*Adaptation, Psychological ; Adolescent ; Adolescent Behavior/*psychology ; Adult ; Child ; Female ; Humans ; Male ; Narcissism ; *Parent-Child Relations ; Parents/*psychology ; Self Efficacy ; Surveys and Questionnaires ; }, abstract = {The quality of the adolescent-parent relationship is closely related to the adolescent's sense of entitlement. Study 1 (458 central-Israel adolescents, 69% girls, ages: 11-16) developed the sense of relational entitlement among adolescents toward their parents (SREap, adapted from the original SRE on adults' romantic relationships) and provided initial validity evidence of its three-factor structure: exaggerated, restricted and assertive - replicating the SRE's factor structure. Studies 2-5 (1237 adolescents, 56% girls) examined the link between the SREap factors and relevant psychological measures. Exaggerated and restricted SREap factors were associated with attachment insecurities. Restricted and exaggerated entitlement factors were related to higher levels of emotional problems, and lower levels of: wellbeing, positive mood and life satisfaction. Conversely, assertive entitlement was related to higher life satisfaction and self-efficacy and lower levels of emotional problems. The findings also indicate that SREap is not merely a form of narcissism. The implications of SREap are discussed.}, } @article {pmid27708222, year = {2016}, author = {Elias, EV and de Castro, NP and Pineda, PH and Abuázar, CS and Bueno de Toledo Osorio, CA and Pinilla, MG and da Silva, SD and Camargo, AA and Silva, WA and E Ferreira, EN and Brentani, HP and Carraro, DM}, title = {Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {46}, pages = {75672-75684}, pmid = {27708222}, issn = {1949-2553}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Disease Progression ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Genetic Association Studies ; Humans ; Neoplasm Staging ; Reproducibility of Results ; *Transcriptome ; }, abstract = {Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients.}, } @article {pmid27702066, year = {2016}, author = {Siciliano, M and Santangelo, G and D'Iorio, A and Basile, G and Piscopo, F and Grossi, D and Trojano, L}, title = {Rouleau version of the Clock Drawing Test: age- and education-adjusted normative data from a wide Italian sample.}, journal = {The Clinical neuropsychologist}, volume = {30}, number = {sup1}, pages = {1501-1516}, doi = {10.1080/13854046.2016.1241893}, pmid = {27702066}, issn = {1744-4144}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Dementia/*diagnosis/epidemiology/*psychology ; *Educational Status ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; *Neuropsychological Tests ; Regression Analysis ; Young Adult ; }, abstract = {OBJECTIVE: The Clock Drawing Test (CDT) is widely used as a screening tool for discriminating cognitively normal individuals from patients with mild dementia. The aim of present study was to provide normative values for a 10-point quantitative scoring system proposed by Rouleau and colleagues (1992), including CDT total score and subscales score assessing representation of clock face (RC), layout of numbers (LN), and position of hands (PH), in a large sample of Italian healthy individuals.

METHOD: Eight hundred and seventy-two Italian healthy participants (483 women; age range 20-94 years) with educational level from primary school to university underwent CDT and Mini Mental State Examination (MMSE).

RESULTS: Multiple linear regression analysis revealed that age and education significantly influenced CDT total score and its subscale scores. Moreover, a significant effect of gender was found only in RC subscale. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-off values were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a weakly significant correlation between adjusted CDT total score and adjusted MMSE scores.

CONCLUSIONS: The present study provided normative data for the Rouleau and colleagues version of CDT in an Italian sample, useful for clinical and research purposes.}, } @article {pmid27700210, year = {2017}, author = {Aysan, E and Idiz, UO and Elmas, L and Saglam, EK and Akgun, Z and Yucel, SB}, title = {Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {30}, number = {3}, pages = {187-192}, doi = {10.1080/08941939.2016.1232449}, pmid = {27700210}, issn = {1521-0553}, mesh = {Adult ; Aged ; Boron/*therapeutic use ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Double-Blind Method ; Female ; Gels ; Humans ; Middle Aged ; Radiodermatitis/*prevention & control ; }, abstract = {AIM: This study is aimed to evaluate the effects of boron on radiation-induced skin reactions (RISR) in breast cancer patients.

MATERIAL AND METHODS: After 47 patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received a boron-based gel, and 24 (51%) received placebo. Assessments were performed according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five-Point Horizontal Scale (FPHS).

RESULTS: At the end of the fifth week of radiotherapy, the RTOG scores in the boron group were significantly lower than those in the placebo group (p = .024). The FPHS score was higher in the placebo group than in the boron group, and this difference was not statistically significant (p = .079).

CONCLUSION: Using the RTOG scoring system, we revealed that the application of a boron-based gel diminished RISR. The mechanism of action is unclear but may be related to antioxidant, wound healing, and thermal degradation effects of boron.}, } @article {pmid27692597, year = {2016}, author = {den Boer, SL and Rizopoulos, D and du Marchie Sarvaas, GJ and Backx, AP and Ten Harkel, AD and van Iperen, GG and Rammeloo, LA and Tanke, RB and Boersma, E and Helbing, WA and Dalinghaus, M}, title = {Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children.}, journal = {The American journal of cardiology}, volume = {118}, number = {11}, pages = {1723-1729}, doi = {10.1016/j.amjcard.2016.08.053}, pmid = {27692597}, issn = {1879-1913}, mesh = {Acute Disease ; Adolescent ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/mortality ; Child ; Child, Preschool ; Chronic Disease ; Death, Sudden, Cardiac/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Natriuretic Peptide, Brain/*blood ; Netherlands/epidemiology ; Peptide Fragments/*blood ; Prognosis ; Retrospective Studies ; *Risk Assessment ; Risk Factors ; Survival Rate/trends ; }, abstract = {N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p <0.001) and a 1.8 times higher risk thereafter (p <0.001). Furthermore, at any time, the slope of log10(NT-proBNP) was significantly predictive for the risk of an end point (0 to 30 days hazard ratio [HR] 3.5, >30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP ≥7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP ≥924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.}, } @article {pmid27690743, year = {2017}, author = {Roth, G and Shane, N and Kanat-Maymon, Y}, title = {Empathising with the enemy: emotion regulation and support for humanitarian aid in violent conflicts.}, journal = {Cognition & emotion}, volume = {31}, number = {8}, pages = {1511-1524}, doi = {10.1080/02699931.2016.1237348}, pmid = {27690743}, issn = {1464-0600}, mesh = {Adult ; Conflict, Psychological ; *Emotions ; *Empathy ; Ethnic Violence/*psychology ; Female ; Humans ; Israel ; Male ; *Relief Work ; Young Adult ; }, abstract = {Considering that negative intergroup emotions can hinder conflict resolution, we proposed integrative emotion regulation (IER) as possibly predicting conciliatory policies towards outgroups in violent conflict. Two studies examined Jewish Israelis' self-reported IER, empathy, liberal attitudes, and support for humanitarian aid to Palestinians in Gaza. Study 1 (N = 298) found that unlike reappraisal Jewish Israelis' ability to explore emotions (e.g. IER) promoted concern for others' emotions (empathy), which in turn predicted support for humanitarian aid (while controlling for education level, and religiosity). Study 2 (N = 291) replicated this mediation model, additionally confirming that liberal attitudes (upholding equal, fair treatment for minorities) moderated the relation between IER and support for humanitarian aid. Thus, IER linked more strongly with humanitarian support when the commitment for liberal egalitarian beliefs was high. Preliminary results hold important theoretical and practical implications regarding the potential to empathise with outgroup members in intractable conflicts.}, } @article {pmid27689969, year = {2016}, author = {Vaidya, JS and Wenz, F and Bulsara, M and Tobias, JS and Joseph, DJ and Saunders, C and Brew-Graves, C and Potyka, I and Morris, S and Vaidya, HJ and Williams, NR and Baum, M}, title = {An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).}, journal = {Health technology assessment (Winchester, England)}, volume = {20}, number = {73}, pages = {1-188}, doi = {10.3310/hta20730}, pmid = {27689969}, issn = {2046-4924}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; }, abstract = {BACKGROUND: Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies.

OBJECTIVE: To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks.

DESIGN: The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world.

SETTING: Thirty-three centres in 11 countries.

PARTICIPANTS: Women who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size.

INTERVENTIONS: TARGIT within a risk-adapted approach and whole-breast EBRT.

MAIN OUTCOME MEASURES: The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality.

RESULTS: In total, 3451 patients were recruited between March 2000 and June 2012. The following values are 5-year Kaplan-Meier rates for TARGIT compared with EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to 5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%; p = 0.04; Pnon-inferiority = 0.00000012] and in the prepathology stratum (n = 2298) when TARGIT was given concurrently with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to 2.5%; p = 0.31; Pnon-inferiority = 0.0000000013). With delayed TARGIT postpathology (n = 1153), the between-group difference was larger than 2.5% and non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to 9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%; p = 0.069; Pnon-inferiority = 0.06640]. The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p = 0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was found to be the only predictor of outcome: hormone-responsive patients (PgR positive) had similar 5-year local recurrence with TARGIT during lumpectomy (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%; p = 0.77). Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%, 95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%; p = 0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to 2.5% vs. 3.5%, 95% CI 2.3% to 5.2%; p = 0.0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI 3.9% to 7.3%; p = 0.099]. Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar quality-adjusted life-years, had a positive incremental net monetary benefit that was borderline statistically significantly different from zero and had a probability of > 90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health-care providers in the UK by £8-9.1 million each year. This does not include environmental, patient and societal costs.

LIMITATIONS: The number of local recurrences is small but the number of events for local recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of so few events (< 3.5%) also implies that both treatments are effective and any difference is unlikely to be large. Not all 3451 patients were followed up for 5 years; however, more than the number of patients required to answer the main trial question (n = 585) were followed up for > 5 years.

CONCLUSIONS: For patients with breast cancer (women who are aged ≥ 45 years with hormone-sensitive invasive ductal carcinoma that is up to 3.5 cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective as, safer than and less expensive than postoperative EBRT.

FUTURE WORK: The analyses will be repeated with longer follow-up. Although this may not change the primary result, the larger number of events may confirm the effect on overall mortality and allow more detailed subgroup analyses. The TARGeted Intraoperative radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as part of postoperative EBRT.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN34086741 and ClinicalTrials.gov NCT00983684.

FUNDING: University College London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and Medical Research Council and German Federal Ministry of Education and Research (BMBF). From September 2009 this project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further project information.}, } @article {pmid27689885, year = {2016}, author = {Kumar, R and Nawroth, PP and Tyedmers, J}, title = {Prion Aggregates Are Recruited to the Insoluble Protein Deposit (IPOD) via Myosin 2-Based Vesicular Transport.}, journal = {PLoS genetics}, volume = {12}, number = {9}, pages = {e1006324}, pmid = {27689885}, issn = {1553-7404}, abstract = {Aggregation of amyloidogenic proteins is associated with several neurodegenerative diseases. Sequestration of misfolded and aggregated proteins into specialized deposition sites may reduce their potentially detrimental properties. Yeast exhibits a distinct deposition site for amyloid aggregates termed "Insoluble PrOtein Deposit (IPOD)", but nothing is known about the mechanism of substrate recruitment to this site. The IPOD is located directly adjacent to the Phagophore Assembly Site (PAS) where the cell initiates autophagy and the Cytoplasm-to-Vacuole Targeting (CVT) pathway destined for delivery of precursor peptidases to the vacuole. Recruitment of CVT substrates to the PAS was proposed to occur via vesicular transport on Atg9 vesicles and requires an intact actin cytoskeleton and "SNAP (Soluble NSF Attachment Protein) Receptor Proteins (SNARE)" protein function. It is, however, unknown how this vesicular transport machinery is linked to the actin cytoskeleton. We demonstrate that recruitment of model amyloid PrD-GFP and the CVT substrate precursor-aminopeptidase 1 (preApe1) to the IPOD or PAS, respectively, is disturbed after genetic impairment of Myo2-based actin cable transport and SNARE protein function. Rather than accumulating at the respective deposition sites, both substrates reversibly accumulated often together in the same punctate structures. Components of the CVT vesicular transport machinery including Atg8 and Atg9 as well as Myo2 partially co-localized with the joint accumulations. Thus we propose a model where vesicles, loaded with preApe1 or PrD-GFP, are recruited to tropomyosin coated actin cables via the Myo2 motor protein for delivery to the PAS and IPOD, respectively. We discuss that deposition at the IPOD is not an integrated mandatory part of the degradation pathway for amyloid aggregates, but more likely stores excess aggregates until downstream degradation pathways have the capacity to turn them over after liberation by the Hsp104 disaggregation machinery.}, } @article {pmid27689750, year = {2016}, author = {Na, N and Luo, Y and Zhao, D and Yang, S and Hong, L and Li, H and Miao, B and Qiu, J}, title = {Prolongation of kidney allograft survival regulated by indoleamine 2, 3-dioxygenase in immature dendritic cells generated from recipient type bone marrow progenitors.}, journal = {Molecular immunology}, volume = {79}, number = {}, pages = {22-31}, doi = {10.1016/j.molimm.2016.09.005}, pmid = {27689750}, issn = {1872-9142}, mesh = {Allografts/immunology ; Animals ; Blotting, Western ; Dendritic Cells/enzymology/*immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Graft Survival ; Hematopoietic Stem Cells/enzymology/immunology ; Immune Tolerance/*immunology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology/metabolism ; *Kidney Transplantation ; Lymphocyte Culture Test, Mixed ; Male ; Rats ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology/*immunology ; }, abstract = {Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4[+]CD25[+]Foxp3[+] regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.}, } @article {pmid27688086, year = {2016}, author = {Wang, D and Fu, L and Shah, W and Zhang, J and Yan, Y and Ge, X and He, J and Wang, Y and Li, X}, title = {Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.}, journal = {Pathology, research and practice}, volume = {212}, number = {12}, pages = {1151-1156}, doi = {10.1016/j.prp.2016.09.009}, pmid = {27688086}, issn = {1618-0631}, mesh = {Breast Neoplasms/genetics/pathology/*virology ; Carcinoma, Ductal, Breast/genetics/pathology/*virology ; DNA, Viral/*genetics ; Female ; Human Papillomavirus DNA Tests ; Humans ; Middle Aged ; Oncogenes/*genetics ; Papillomaviridae/*genetics ; Papillomavirus Infections/virology ; }, abstract = {BACKGROUND AND AIMS: The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH).

METHODS: One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC).

RESULTS: HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731).

CONCLUSIONS: HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.}, } @article {pmid27686301, year = {2016}, author = {Bano, R and Khan, AI and Zafar, W and Zaidi, AA and Zaidi, AA and Chaudhry, MZ and Khan, HM}, title = {Breast cancer treatment in high-risk elderly patients: A challenging situation and difficult decisions.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {66}, number = {10}, pages = {1267-1271}, pmid = {27686301}, issn = {0030-9982}, mesh = {Age of Onset ; Aged ; Aged, 80 and over ; Breast Neoplasms/*therapy ; Breast Neoplasms, Male/therapy ; Cancer Care Facilities ; *Decision Making ; Female ; Humans ; Male ; Pakistan ; Retrospective Studies ; }, abstract = {OBJECTIVE: To assess whether high-risk elderly patients with aggressive tumour biology can be offered standard treatment despite having multiple comorbid conditions.

METHODS: This retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of breast cancer patients aged 65 years or above treated between 2006 and 2012,. Data was collected regarding patients' demographics, baseline clinical characteristics, comorbidities, treatment and outcomes. Stata 12 was used for data analysis.

RESULTS: Of the 407 patients in the study, 399(98%) were women and 8(2%) were men. The overall mean age at diagnosis was 70±4.9 years (range: 65-90 years). Overall, 59(14.5%) participants had family history of breast cancer. Bilateral disease was seen in 17(4.2%). Invasive ductal carcinoma was seen in 299(73.5%). Besides, 101(24.8%) patients had no comorbid conditions, while 138(34%) had one, 102(25%) had two and 66(16%) had three or more comorbid conditions. There was no statistically significant difference between those receiving standard treatment including surgery or other modalities.

CONCLUSIONS: Elderly patients of breast cancer may be offered treatment according to the tumour biology and their overall functional status.}, } @article {pmid27685526, year = {2016}, author = {Naleskina, LA and Lukianova, NY and Sobchenko, SO and Storchai, DM and Chekhun, VF}, title = {Lactoferrin expression in breast cancer in relation to biologic properties of tumors and clinical features of disease.}, journal = {Experimental oncology}, volume = {38}, number = {3}, pages = {181-186}, pmid = {27685526}, issn = {2312-8852}, mesh = {Aged ; Breast/*pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Lactoferrin/*analysis ; Middle Aged ; Prognosis ; Prospective Studies ; Receptors, Estrogen/analysis ; Retrospective Studies ; }, abstract = {UNLABELLED: To determine the patterns of lactoferrin (LF) expression in breast cancer (BC) in relation to biologic properties of the neoplasms and clinical features of the disease course.

MATERIALS AND METHODS: Clinical specimens of 266 BC patients (115 patients with BC of stages I-II - retrospective study, and 151 BC patients - prospective study) were analyzed. Morphological, immunohistochemical and statistical methods were used.

RESULTS: The number of LF-positive tumors in retrospective and prospective groups was similar (52.1 and 52.8%, respectively). Among common clinical criteria for prognosis of the disease outcome in BC patients (patient's age; stage of the disease; histological type, differentiation grade, receptor status; presence of metastases), a strong correlation was found only between expression indexes of LF and estrogen receptors (ER). In ER-positive tumors expression of LF was significantly higher than in ER-negative tumors (35 vs 18%). 5-Year survival rate of BC patients was higher in LF-positive group (70 vs 52% in LF-negative group). The presence of regional metastasis tended to correlate with an increased number of LF-positive tumors. In the patients with invasive ductal carcinoma, expression level of LF moderately correlated with occurrence of luminal A subtype (r = 0.43), while in the patients with invasive lobular carcinoma this index strongly correlated with occurrence of luminal B subtype (r = 0.71). LF expression correlated positively with low and moderate differentiation grade of luminal B or basal tumors, and negatively with luminal B or basal tumors of high differentiation grade (r = -0.57 and -0.63, respectively).

CONCLUSION: It has been shown that LF expression in breast tumors correlated with life expectancy of BC patients and important physiologic and clinical features of the disease, while the character of such relation strongly depended on molecular phenotype of tumor, i.e. luminal A, luminal B or basal.}, } @article {pmid27683971, year = {2017}, author = {Detremerie, C and Timmermans, F and De Pauw, M and Gheeraert, P and Hemelsoet, D and Toeback, J and Bové, T and Vandecasteele, E}, title = {Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.}, journal = {Acta clinica Belgica}, volume = {72}, number = {4}, pages = {268-273}, doi = {10.1080/17843286.2016.1219012}, pmid = {27683971}, issn = {2295-3337}, mesh = {Aged ; Breast Neoplasms/*complications/*diagnosis ; Carcinoma, Ductal, Breast/*complications/*diagnosis ; Endocarditis, Non-Infective/diagnostic imaging/*etiology ; Female ; Humans ; Stroke/diagnostic imaging/*etiology ; }, abstract = {We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.}, } @article {pmid27682634, year = {2016}, author = {Pellecchia, MT and Savastano, R and Moccia, M and Picillo, M and Siano, P and Erro, R and Vallelunga, A and Amboni, M and Vitale, C and Santangelo, G and Barone, P}, title = {Lower serum uric acid is associated with mild cognitive impairment in early Parkinson's disease: a 4-year follow-up study.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {123}, number = {12}, pages = {1399-1402}, pmid = {27682634}, issn = {1435-1463}, mesh = {Aged ; Cognitive Dysfunction/*blood/diagnostic imaging/*etiology ; Female ; Humans ; Italy ; Logistic Models ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/blood/*complications/diagnostic imaging ; Severity of Illness Index ; Tomography, X-Ray Computed ; Uric Acid/*metabolism ; }, abstract = {Cognitive deficits are common in Parkinson's disease (PD) and many patients eventually develop dementia; however, its occurrence is unpredictable. Serum uric acid (UA) has been proposed as a biomarker of PD, both in the preclinical and clinical phase of the disease. The aim of this pilot study was to evaluate relationships between baseline serum UA levels and occurrence of mild cognitive impairment (MCI) at 4-year follow-up in a cohort of early PD patients. Early PD patients, not presenting concomitant diseases, cognitive impairment or treatment possibly interfering with UA levels, underwent neuropsychological testing at baseline and 4-year follow-up. UA levels were determined in serum at baseline. MCI was found in 23 out of 42 PD patients completing 4-year follow-up. Patients presenting MCI had significantly higher age at onset and lower Frontal Assessment Battery scores at baseline as compared with patients cognitively intact. Logistic regression analysis showed that both serum UA levels (OR = 0.54, p = 0.044) and age (OR = 1.16, p = 0.009) contribute to the occurrence of MCI at 4-year follow-up. Our pilot study suggests that lower levels of serum UA in the early disease stages are associated to the later occurrence of MCI. These results need to be confirmed by further studies on larger samples.}, } @article {pmid27672335, year = {2016}, author = {Luo, S and Chen, J and Mo, X}, title = {The association of PTEN hypermethylation and breast cancer: a meta-analysis.}, journal = {OncoTargets and therapy}, volume = {9}, number = {}, pages = {5643-5650}, pmid = {27672335}, issn = {1178-6930}, abstract = {OBJECTIVE: Phosphatase and tensin homolog (PTEN) deleted on chromosome 10, as a tumor suppressor gene, is crucial for the development of both familial and sporadic breast cancer (BC). The aim of this study was to perform a meta-analysis to evaluate the clinicopathological significance of PTEN promoter hypermethylation in BC.

METHODS: A comprehensive literature search was made in PubMed, Embase, Google Scholar, Chinese database (China National Knowledge Infrastructure [CNKI]), and Web of Science. The analysis of pooled data was performed with Review Manager 5.2. The fixed-effects or random-effects models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: The meta-analysis included eight studies and a total of 923 patients. The frequency of PTEN promoter hypermethylation was significantly increased in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) compared to normal breast tissues (OR =22.53, P=0.0002 and OR =22.86, P<0.00001, respectively). However, the frequency of PTEN promoter hypermethylation was similar between IDC and DCIS. Additionally, PTEN methylation was not significantly correlated to estrogen receptor (ER) or human epidermal growth factor type 2 (HER-2) status in patients with BC.

CONCLUSION: PTEN promoter hypermethylation is significantly associated with the risk of DCIS and IDC, suggesting PTEN promoter hypermethylation is a valuable biomarker for diagnosis of BC.}, } @article {pmid27672329, year = {2016}, author = {Cihan, YB and Sarigoz, T}, title = {Role of postmastectomy radiation therapy in breast cancer patients with T1-2 and 1-3 positive lymph nodes.}, journal = {OncoTargets and therapy}, volume = {9}, number = {}, pages = {5587-5595}, pmid = {27672329}, issn = {1178-6930}, abstract = {OBJECTIVE: To evaluate the role of radiotherapy (RT) in overall survival (OS) and disease-free survival in postmastectomy breast cancer patients with tumor size <5 cm, with 1-3 involved axillary lymph nodes (T1-2N1).

PATIENTS AND METHODS: We conducted a retrospective study of 89 postmastectomy patients with T1-2N1 disease between 2005 and 2015 at the Radiation Oncology Clinic of Kayseri Training and Research Hospital. Clinicopathologic, demographic, and laboratory findings, as well as treatment regimens were investigated. OS and disease-free survival as well as factors that can be valuable in the prognosis were evaluated.

RESULTS: A total of 89 female patients with an average age of 53 years (range: 30-81 years) were included in the assessment. Five-year and 10-year local recurrence rates were found to be 6.6% in the RT group and 7.1% in the non-RT group. In the RT group, the mean OS was 110.3 months and progression-free survival was 104.4 months. In the non-RT group, the corresponding figures were 104.3 months and 92.1 months, respectively. Statistically significant correlation was observed between RT and the American Joint Committee on Cancer stage (P<0.001), histological type (P=0.013), tumor size (P<0.001), and lymph node metastasis (P<0.001). During the assessment, locoregional recurrence and/or distant metastasis occurred in nine patients (10%). Locoregional recurrence was observed mostly in patients with invasive ductal carcinoma, tumor >3.0 cm in size, grade II tumors, and perinodal invasion, and who were premenopausal at the time of diagnosis.

CONCLUSION: In T1-2N1 breast cancer patients who underwent modified radical mastectomy, when the effects of postmastectomy RT were evaluated, there were no differences in terms of OS and progression-free survival. In addition, when subgroup analysis was made, in patients with invasive ductal carcinoma, tumor diameter >2 cm, three lymph node metastasis, and stage 2b, postmastectomy RT was seen to be useful.}, } @article {pmid27670952, year = {2017}, author = {Firat, D and Ozturk, G and Demirbas, E and Idiz, O and Isik, A and Eken, H}, title = {Auto-Amputation of the Breast; a Rare Case Caused by Invasive Ductal Carcinoma.}, journal = {The breast journal}, volume = {23}, number = {1}, pages = {102-103}, doi = {10.1111/tbj.12696}, pmid = {27670952}, issn = {1524-4741}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; }, } @article {pmid27668497, year = {2016}, author = {Lee, HS and Ha, JY and Choi, W and Yoon, KC}, title = {Bilateral Corneal Epithelial Lesions Associated with Paclitaxel.}, journal = {Optometry and vision science : official publication of the American Academy of Optometry}, volume = {93}, number = {10}, pages = {1333-1336}, doi = {10.1097/OPX.0000000000000945}, pmid = {27668497}, issn = {1538-9235}, abstract = {PURPOSE: An antineoplastic drug, paclitaxel, is widely used in small cell lung cancer, breast cancer, and ovarian cancer. We report a case of bilateral, vision-impairing corneal epithelial lesions that developed in a patient receiving paclitaxel monotherapy for breast cancer.

CASE REPORT: A 45-year-old woman presented with a 1-month history of bilateral visual disturbances. She had been receiving paclitaxel chemotherapy after modified radical mastectomy for invasive ductal carcinoma in her left breast. Best-corrected visual acuity was 20/100 in the right eye and 20/40 in the left eye. Slit-lamp examination revealed irregular triangular corneal lesions in both eyes. The lesions extended to the center of the cornea involving the visual axis and showed late staining with fluorescein dye. The lesions resolved 5 months after discontinuation of paclitaxel chemotherapy, and best-corrected visual acuity was restored to 20/20 in both eyes.

CONCLUSIONS: Microtubule-stabilizing chemotherapeutic drugs such as paclitaxel can cause visually significant corneal lesions, and these lesions appear to be reversible with discontinuation of the drug. This case highlights the need for regular ophthalmologic examinations for the detection of this reversible adverse ocular reaction.}, } @article {pmid27666605, year = {2016}, author = {Badan, GM and Piato, S and Roveda, D and de Faria Castro Fleury, E}, title = {Predictive values of BI-RADS(®) magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS).}, journal = {European journal of radiology}, volume = {85}, number = {10}, pages = {1701-1707}, doi = {10.1016/j.ejrad.2016.07.010}, pmid = {27666605}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/diagnostic imaging/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Calcinosis/diagnosis ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Early Detection of Cancer ; Female ; Humans ; *Magnetic Resonance Imaging/methods ; *Mammography/methods ; Middle Aged ; Prospective Studies ; }, abstract = {PURPOSE: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI.

MATERIALS AND METHODS: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy.

RESULTS: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%.

CONCLUSION: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases.}, } @article {pmid27657985, year = {2016}, author = {Toffoletto, O and Afiune, J and Thiemann, JE and Khandave, SS and Patel, S and Rodrigues, DG}, title = {Comparative pharmacokinetic and pharmacodynamic evaluation between a new biosimilar and reference recombinant human growth hormone.}, journal = {Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society}, volume = {30-31}, number = {}, pages = {31-36}, doi = {10.1016/j.ghir.2016.09.003}, pmid = {27657985}, issn = {1532-2238}, mesh = {Adult ; Biosimilar Pharmaceuticals/*pharmacology ; Female ; Healthy Volunteers ; Human Growth Hormone/metabolism/*pharmacology ; Humans ; Insulin-Like Growth Factor Binding Protein 3/*drug effects/metabolism ; Insulin-Like Growth Factor I/*drug effects/metabolism ; Male ; Recombinant Proteins/metabolism/*pharmacology ; }, abstract = {OBJECTIVE: To extend available dosing options in the treatment of growth hormone deficiency, a comparative pharmacokinetic and pharmacodynamic phase-1 clinical study involving subcutaneous administration of growth hormone was conducted.

DESIGN: The test formulation (biosimilar recombinant human growth hormone; r-hGH; Somatotropin) and reference formulation (Genotropin®) were tested in 38 adult healthy subjects after their subcutaneous administration of 12.8IU in an open label, single dose, randomized, two period cross over study separated with a washout period of 11days. Endogenous growth hormone release was suppressed by a continuous Octreotide infusion up to 24h after r-hGH administration. All the subjects were evaluated for local tolerance using Wong-Baker Faces pain rating scale and an injection site reaction (ISR) score. Detection of serum levels of r-hGH, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was done by suitable validated bio-analytical methods. Assessment of bioequivalence for pharmacokinetic parameters was done using log-transformed area under the curve (AUC) and maximum concentration (Cmax) for r-hGH. The pharmacodynamic assessment was done by comparing the area under the effect-time curve (AUEClast) and maximum measured effect concentration (Emax) of IGF-1 and IGFBP-3.

RESULTS: The biosimilar formulation of recombinant human growth hormone fulfilled the predefined bioequivalence criteria for pharmacokinetic and pharmacodynamic parameters.

CONCLUSION: The new biosimilar recombinant human growth hormone bears the potential to become an alternative option for the treatment of growth hormone deficiency.}, } @article {pmid27656399, year = {2016}, author = {Giroud, M and Pisani, DF and Karbiener, M and Barquissau, V and Ghandour, RA and Tews, D and Fischer-Posovszky, P and Chambard, JC and Knippschild, U and Niemi, T and Taittonen, M and Nuutila, P and Wabitsch, M and Herzig, S and Virtanen, KA and Langin, D and Scheideler, M and Amri, EZ}, title = {miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function.}, journal = {Molecular metabolism}, volume = {5}, number = {8}, pages = {615-625}, pmid = {27656399}, issn = {2212-8778}, abstract = {OBJECTIVE: In rodents and humans, besides brown adipose tissue (BAT), islands of thermogenic adipocytes, termed "brite" (brown-in-white) or beige adipocytes, emerge within white adipose tissue (WAT) after cold exposure or β3-adrenoceptor stimulation, which may protect from obesity and associated diseases. microRNAs are novel modulators of adipose tissue development and function. The purpose of this work was to characterize the role of microRNAs in the control of brite adipocyte formation.

METHODS/RESULTS: Using human multipotent adipose derived stem cells, we identified miR-125b-5p as downregulated upon brite adipocyte formation. In humans and rodents, miR-125b-5p expression was lower in BAT than in WAT. In vitro, overexpression and knockdown of miR-125b-5p decreased and increased mitochondrial biogenesis, respectively. In vivo, miR-125b-5p levels were downregulated in subcutaneous WAT and interscapular BAT upon β3-adrenergic receptor stimulation. Injections of an miR-125b-5p mimic and LNA inhibitor directly into WAT inhibited and increased β3-adrenoceptor-mediated induction of UCP1, respectively, and mitochondrial brite adipocyte marker expression and mitochondriogenesis.

CONCLUSION: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.}, } @article {pmid27648361, year = {2016}, author = {Suárez-Arroyo, IJ and Feliz-Mosquea, YR and Pérez-Laspiur, J and Arju, R and Giashuddin, S and Maldonado-Martínez, G and Cubano, LA and Schneider, RJ and Martínez-Montemayor, MM}, title = {The proteome signature of the inflammatory breast cancer plasma membrane identifies novel molecular markers of disease.}, journal = {American journal of cancer research}, volume = {6}, number = {8}, pages = {1720-1740}, pmid = {27648361}, issn = {2156-6976}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; G12 MD007583/MD/NIMHD NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; P20 RR016470/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; F31 CA174307/CA/NCI NIH HHS/United States ; U54 MD008149/MD/NIMHD NIH HHS/United States ; G12 RR003035/RR/NCRR NIH HHS/United States ; SC3 GM111171/GM/NIGMS NIH HHS/United States ; R01 CA178509/CA/NCI NIH HHS/United States ; R25 GM110513/GM/NIGMS NIH HHS/United States ; }, abstract = {Inflammatory Breast Cancer (IBC) is the most lethal form of breast cancer with a 35% 5-year survival rate. The accurate and early diagnosis of IBC and the development of targeted therapy against this deadly disease remain a great medical challenge. Plasma membrane proteins (PMPs) such as E-cadherin and EGFR, play an important role in the progression of IBC. Because the critical role of PMPs in the oncogenic processes they are the perfect candidates as molecular markers and targets for cancer therapies. In the present study, Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) followed by mass spectrometry analysis was used to compare the relative expression levels of membrane proteins (MP) between non-cancerous mammary epithelial and IBC cells, MCF-10A and SUM-149, respectively. Six of the identified PMPs were validated by immunoblotting using the membrane fractions of non-IBC and IBC cell lines, compared with MCF-10A cells. Immunohistochemical analysis using IBC, invasive ductal carcinoma or normal mammary tissue samples was carried out to complete the validation method in nine of the PMPs. We identified and quantified 278 MPs, 76% of which classified as PMPs with 1.3-fold or higher change. We identified for the first time the overexpression of the novel plasminogen receptor, PLGRKT in IBC and of the carrier protein, SCAMP3. Furthermore, we describe the positive relationship between L1CAM expression and metastasis in IBC patients and the role of SCAMP3 as a tumor-related protein. Overall, the membrane proteomic signature of IBC reflects a global change in cellular organization and suggests additional strategies for cancer progression. Together, this study provides insight into the specialized IBC plasma membrane proteome with the potential to identify a number of novel therapeutic targets for IBC.}, } @article {pmid27648124, year = {2016}, author = {Mohan, N and Black, JO and Schwartz, MR and Zhai, QJ}, title = {Invasive ductal carcinoma with in situ pattern: how to avoid this diagnostic pitfall?.}, journal = {American journal of translational research}, volume = {8}, number = {8}, pages = {3337-3341}, pmid = {27648124}, issn = {1943-8141}, abstract = {Although the microscopic features of invasion are usually readily recognized, occasionally invasive ductal carcinoma may mimic the pattern of comedo ductal carcinoma in situ (DCIS) by forming large cellular nests with circumscribed borders, but lacking a definitive myoepithelial cell layer. In these cases, the histologic pattern may appear deceptively noninvasive and the absence of a myoepithelial layer can be easily overlooked. We prospectively examined 10 cases of high grade DCIS. P63, smooth muscle actin, muscle specific actin and calponin immunohistochemical stains were used to identify the presence of myoepithelial cells. In our study, 20% of apparent high grade DCIS cases did not exhibit a myoepithelial layer surrounding large, solid nests with comedo necrosis. Since invasion is defined by the absence of a myoepithelial layer, these results suggest that a DCIS-like pattern may actually represent invasive disease in some cases. Immunohistochemical studies may be essential in making this distinction and in avoiding the potential diagnostic pitfall.}, } @article {pmid27648060, year = {2016}, author = {Li, H and Zhang, S and Wang, Q and Zhu, R}, title = {Clinical value of mammography in diagnosis and identification of breast mass.}, journal = {Pakistan journal of medical sciences}, volume = {32}, number = {4}, pages = {1020-1025}, pmid = {27648060}, issn = {1682-024X}, abstract = {OBJECTIVE: To study the effect and clinical value of mammography in the diagnosis of breast lump so as to improve the diagnosis level of breast cancer.

METHODS: A retrospective analysis was carried out on clinical data of 110 patients with mammary lump confirmed by pathology to study the compliance of mammography diagnosis and Pathology diagnosis in breast lump, and the detection of microcalcifications, phyllode, and observe the image performance of mammography. Taking infitrating ductal carcinoma (IDC) as an example, the correlation of image performance and clinical pathological features of different types was studied so as to predict if mammography performance was effective in the treatment and prognosis in breast cancer.

RESULTS: Taking Breast Imaging Reporting and Data System (BI-RADS) grade 4A as the critical point, the sensitivity, specificity and accuracy of mammography was 90.80% (109/120), 84.60% (126/149) and 87.40% (235/269); taking BI-RADS grade 4B as the critical point, the sensitivity, specificity and accuracy of mammography was 85.00% (102/120), 93.30% (139/149) and 89.60% (241/269); the correlation analysis suggested that, there was some kind of correlation between the mammography performance and clinical features of breast cancer.

CONCLUSION: Mammography is worth being promoted in clinic for its significant clinical value in diagnosing and identifying breast lump.}, } @article {pmid27645144, year = {2017}, author = {Yoo, J and Yoon, HJ and Kim, BS}, title = {Prognostic value of primary tumor SUVmax on F-18 FDG PET/CT compared with semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.}, journal = {Annals of nuclear medicine}, volume = {31}, number = {1}, pages = {19-28}, doi = {10.1007/s12149-016-1127-2}, pmid = {27645144}, issn = {1864-6433}, mesh = {Adult ; Aged ; Biological Transport ; Breast/*diagnostic imaging/metabolism/pathology ; Breast Density ; Carcinoma, Ductal, Breast/diagnosis/*diagnostic imaging/*metabolism ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Middle Aged ; Organ Specificity ; *Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Technetium Tc 99m Sestamibi/*metabolism ; }, abstract = {OBJECTIVE: This study aimed to evaluate the prognostic value of F-18 FDG PET/CT in comparison with Tc-99m sestamibi breast-specific gamma imaging (BSGI) and previously established clinical prognostic parameters of invasive ductal breast carcinoma (IDC).

METHODS: We retrospectively included 157 female IDC patients (mean age 49.2 years, range 29.9-78.9) who underwent PET/CT and BSGI. The maximum standardized uptake value (SUVmax) and tumor to normal background ratios (TNRs) of their primary tumors were measured on PET/CT and BSGI, respectively. Univariate and multivariate survival analyses were performed to evaluate the prognostic value of the measured parameters and other clinical prognostic factors: age, menopausal status, breast density, pathologic tumor size (pTS), axillary nodal status (ANS), nuclear grade, histologic grade, hormone receptor status of estrogen (ER) and progesterone receptors (PR) and HER-2 expression.

RESULTS: Among 157 patients, recurrences occurred in 22 patients (14.0 %). In univariate analyses, pTS (p < 0.0001), ANS (p < 0.0001), nuclear grade (p = 0.0046), histologic grade (p = 0.0001), ER status (p < 0.0001), PR status (p = 0.0037), HER-2 status (p = 0.0007), primary tumor SUVmax (p < 0.0001) and TNR (p = 0.0001) were significant predictors of recurrence. Among them, pTS (p = 0.0172), ANS (p = 0.0416), ER status (p = 0.0375) and primary tumor SUVmax (p = 0.0239) were independent prognostic factors in multivariate regression analysis.

CONCLUSIONS: High primary tumor SUVmax of PET/CT and high TNR of BSGI were poor prognostic factors in IDC patients; in addition, primary tumor SUVmax was an independent prognostic factor along with pTS, ANS and ER status.}, } @article {pmid27643483, year = {2017}, author = {Goldschmied, N and Sheptock, M and Kim, K and Galily, Y}, title = {Appraising Loftus and Palmer (1974) post-event information versus concurrent commentary in the context of sport.}, journal = {Quarterly journal of experimental psychology (2006)}, volume = {70}, number = {11}, pages = {2347-2356}, doi = {10.1080/17470218.2016.1237980}, pmid = {27643483}, issn = {1747-0226}, mesh = {Adolescent ; Adult ; Analysis of Variance ; *Comprehension ; Female ; Humans ; Male ; Perception ; *Persuasive Communication ; Sports/*psychology ; Verbal Behavior/*physiology ; Young Adult ; }, abstract = {Two experiments were conducted to examine framing effects in sport. In Experiment 1, a conceptual replication [Loftus, E. F., & Palmer, J. C. (1974). Reconstruction of automobile destruction: An example of the interaction between language and memory. Journal of Verbal Learning and Verbal Behavior, 13(5), 585-589], participants watched a hockey collision, with the hit described later in a written format as a "contact", "bump", or "smash". This manipulation resulted in no differences in participants' report of how fast the players were skating, their intentions, and the outcome of the hit. In Experiment 2, participants watched the same video clip with ongoing commentary. Those who heard the announcer describing the event as "contact" estimated a higher skating speed than participants who were exposed to the "smash" commentary. Participants who were exposed to the "bump" commentary rated the repercussions of the collision as less severe than did those exposed to the other commentaries. These findings show that the perception of magnitude hierarchy may be domain specific and suggest future avenues for exploring framing effects when one is exposed to visual stimuli.}, } @article {pmid27638679, year = {2016}, author = {Ali-Mucheru, M and Pockaj, B and Patel, B and Pizzitola, V and Wasif, N and Stucky, CC and Gray, R}, title = {Contrast-Enhanced Digital Mammography in the Surgical Management of Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {23}, number = {Suppl 5}, pages = {649-655}, doi = {10.1245/s10434-016-5567-7}, pmid = {27638679}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology/surgery ; Carcinoma, Lobular/*diagnostic imaging/pathology/surgery ; Clinical Decision-Making ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography/*methods ; Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Contrast-enhanced digital mammography (CEDM) is a new breast imaging technique. The role of CEDM in the surgical management of breast cancer has not yet been characterized.

METHODS: A retrospective review of prospective breast surgery and breast imaging databases for patients who underwent CEDM and had breast cancer surgery.

RESULTS: A total of 351 patients had CEDM; 128 had malignant lesions, and 101 of these underwent surgery with 105 malignancies identified. The mean age was 62 years (range 25-85 years). The histology was 65 % invasive ductal carcinoma, 16 % invasive lobular carcinoma, 11 % ductal carcinoma-in situ, 3 % mixed invasive ductal carcinoma/invasive lobular carcinoma, and 5 % other histologies. After excluding two lesions that had been removed before the examination, CEDM identified 98 % (n = 101/103) of the index lesions. The two lesions not identified were Paget disease only and a parasternal lesion too medial to include in the field of view. CEDM led to additional biopsies in 12 % (n = 12) of patients. Of these, 67 % (n = 8) proved to be invasive carcinoma and 33 % (n = 4) were benign. CEDM changed surgical management in 20 % (n = 20) of cancer patients with a 4 % (n = 4) rate of conversion to mastectomy.

CONCLUSIONS: Among patients undergoing surgical therapy for breast cancer, CEDM was highly sensitive, had size measurements that correlated well with histologic size, and produced a relatively low rate of false-positive additional biopsy findings. CEDM appears to be promising as an alternative to magnetic resonance imaging in the surgical planning of these patients.}, } @article {pmid27638188, year = {2016}, author = {Ben-David, BM and Moral, MI and Namasivayam, AK and Erel, H and van Lieshout, PHHM}, title = {Linguistic and emotional-valence characteristics of reading passages for clinical use and research.}, journal = {Journal of fluency disorders}, volume = {49}, number = {}, pages = {1-12}, doi = {10.1016/j.jfludis.2016.06.003}, pmid = {27638188}, issn = {1873-801X}, mesh = {Emotions/*physiology ; Female ; Humans ; Linguistics/*methods ; Male ; *Reading ; Research Design ; }, abstract = {PURPOSE: Fluency assessment in people who stutter (PWS) includes reading aloud passages. There is little information on properties of these passages that may affect reading performance: emotional valance, arousal, word familiarity and frequency and passage-readability. Our first goal was to present an extensive examination of these factors in three commonly used (“traditional”) passages. The second goal was to compare a traditional passage to a new passage, designed to minimize the impact of these properties.

METHODS: Content words were rated (129 participants) on arousal, valence and familiarity. Other linguistic features were analyzed based on available datasets. This information was used to assess traditional passages, and to construct a new well-balanced passage, made of neutral, low-arousal and highly-familiar words. Readability for all passages was tested using formula-based and CLOZE tests (31 participants). Finally, 26 PWS were evaluated on fluency comparing the commonly used “Rainbow” passage with the novel one.

RESULTS: The three traditional passages contain a share of emotionally valenced (22-34%), high arousal (15-18%), lower familiarity (6-8%) and polysyllabic (5-9%) content words. Readability was highest for the novel passage (on formula-based scales). Average disfluencies percent for the Rainbow and our novel passage were not significantly different. Yet half of the individuals in this sample showed a large difference between the two passages.

CONCLUSION: We provide detailed information on potential sources of variance using the traditional passages. Knowledge about these characteristics can inform clinical practice (and research). We suggest a combined procedure, using more than one passage to assess stuttering in individual cases.}, } @article {pmid27630851, year = {2016}, author = {Panda, KM and Naik, R}, title = {A Clinicopathological Study of Benign Phyllodes Tumour of Breast with Emphasis on Unusual Features.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {10}, number = {7}, pages = {EC14-7}, pmid = {27630851}, issn = {2249-782X}, abstract = {INTRODUCTION: Benign Phyllodes Tumours (PTs) are rare fibroepithelial neoplasms that resemble fibroadenoma. But unlike fibroadenoma, benign PT can recur and both stromal & epithelial components can progress to malignancy. Contrary to earlier belief that benign PT is a stromal neoplasm and possibly arises from fibroadenoma, more recent molecular studies have suggested that both stroma and epithelium can become neoplastic. Sometimes, benign PT can occur synchronously with fibroadenoma. Here histomorphologic analysis of eleven cases of benign PT are presented including some unusual features.

MATERIALS AND METHODS: Eleven cases of benign PT diagnosed between Dec 2014 and Jan 2016 in the Department of Pathology were studied. The demographic and clinicopathological features were analysed.

RESULTS: The most common age group affected was 20-30 years (range: 13-45). Clinical features included pain, lump and bleeding from nipple. The tumour size varied from 2.5-18 cm in diameter. H&E stained sections showed secondary changes (haemorrhage, myxoid, change, cystic degeneration), epithelial hyperplasia (8), squamous & columnar metaplasia (1), benign tubular adenoma like areas (1), Ductal Carcinoma In Situ (DCIS) (1), Invasive Ductal Carcinoma (IDC) (1), Pseudoangiomatous Stromal Hyperplasia (PASH) (1), histologic infarction (2), tumour necrosis (1) and synchronous fibroadenoma (1). Unusual histologic features included atypical ductal hyperplasia, DCIS, IDC, synchronous fibroadenoma and tubular adenoma like areas arising within benign PT.

CONCLUSION: This study shows a spectrum of hyperplastic, metaplastic, dysplastic, benign, in-situ-malignancy and even invasive ductal malignancy occurring in benign PT. Therefore adequate and extensive sampling is recommended for accurate diagnosis.}, } @article {pmid27630343, year = {2016}, author = {Do, SI and Yoon, G and Kim, HS and Kim, K and Lee, H and Do, IG and Kim, DH and Chae, SW and Sohn, JH}, title = {Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.}, journal = {Anticancer research}, volume = {36}, number = {9}, pages = {4873-4882}, doi = {10.21873/anticanres.11051}, pmid = {27630343}, issn = {1791-7530}, mesh = {Adult ; Aged ; Biomarkers, Tumor/biosynthesis/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/biosynthesis/*genetics ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/pathology ; Nuclear Proteins/biosynthesis/*genetics ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {BACKGROUND: Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood.

MATERIALS AND METHODS: We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC.

RESULTS: Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease.

CONCLUSION: BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes.}, } @article {pmid27628551, year = {2016}, author = {Hamaoka, A and Matsuda, T and Konishi, E and Taguchi, T}, title = {[A Case of Luminal-HER2 Advanced Breast Cancer with Liver Metastasis Showed Pathological Complete Response to the Therapy with Pertuzumab plus Trastuzumab plus Docetaxel].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {9}, pages = {1097-1100}, pmid = {27628551}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenobarbital/analysis/metabolism ; Receptor, ErbB-2/analysis/metabolism ; Taxoids/administration & dosage ; Trastuzumab/administration & dosage ; Treatment Outcome ; }, abstract = {A 56-year-old woman noticed a mass on her left breast and visited our hospital. An irregular mass of 3 cm with associated axillary lymphadenopathy was detected under the nipple of the left breast. After further evaluations, the diagnosis was an invasive ductal carcinoma(scirrhous carcinoma)ofLuminal -HER2 type with liver metastases(cT4bN1M1, Stage IV). Treatment was initiated with a combination ofpertuzumab, trastuzumab, and docetaxel(PTD). The primary tumor showed a clinical complete response, and the liver metastases and the axillary lymph node metastases showed a partial response. Docetaxel was excluded after the 8th cycle because the patient experienced severe edema. After 15 cycles of therapy, the primary tumor was resected, and pathological examination revealed a pathological complete response ofthe primary lesion. Thus, PTD combination therapy is effective for Stage IV metastatic breast cancer ofthe Luminal-HER2 type.}, } @article {pmid27626636, year = {2016}, author = {Fan, LC and Jeng, YM and Lu, YT and Lien, HC}, title = {SPOCK1 Is a Novel Transforming Growth Factor-β-Induced Myoepithelial Marker That Enhances Invasion and Correlates with Poor Prognosis in Breast Cancer.}, journal = {PloS one}, volume = {11}, number = {9}, pages = {e0162933}, pmid = {27626636}, issn = {1932-6203}, mesh = {Biomarkers, Tumor/metabolism ; Blotting, Western ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/physiology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Prognosis ; Proportional Hazards Models ; Proteoglycans/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis ; Transforming Growth Factor beta/physiology ; }, abstract = {In addition to contraction, myoepithelia have diverse paracrine effects, including a tumor suppression effect. However, certain myoepithelial markers have been shown to contribute to tumor progression. Transforming growth factor-β (TGF-β) is involved in the transdifferentiation of fibroblasts to contractile myofibroblasts. We investigated whether TGF-β can upregulate potential myoepithelial markers, which may have functional and clinicopathological significance in breast cancer. We found that TGF-β induced SPOCK1 expression in MCF10A, MCF12A, and M10 breast cells and demonstrated SPOCK1 as a novel myoepithelial marker that was immunolocalized within or beneath myoepithelia lining ductolobular units. A functional study showed that overexpression of SPOCK1 enhanced invasiveness in mammary immortalized and cancer cells. To further determine the biological significance of SPOCK1 in breast cancer, we investigated the expression of SPOCK1 in 478 invasive ductal carcinoma (IDC) cases through immunohistochemistry and correlated the expression with clinicopathological characteristics. SPOCK1 expression was significantly correlated with high pathological tumor size (P = 0.012), high histological grade (P = 0.013), the triple-negative phenotype (P = 0.022), and the basal-like phenotype (P = 0.026) and was correlated with a significantly poorer overall survival on univariate analysis (P = 0.001, log-rank test). Multivariate Cox regression analysis demonstrated that SPOCK1 expression maintained an independent poor prognostic factor of overall survival. Analysis of SPOCK1 expression on various non-IDC carcinoma subtypes showed an enrichment of SPOCK1 expression in metaplastic carcinoma, which is pathogenetically closely related to epithelial-mesenchymal transition (EMT). In conclusion, we identified SPOCK1 as a novel TGF-β-induced myoepithelial marker and further demonstrated that SPOCK1 enhanced invasion in breast cancer cells and correlated with poor prognosis in breast cancer clinical samples. The enrichment of SPOCK1 expression in metaplastic carcinoma and the correlation between SPOCK1 expression and high histological grading and basal-like phenotypes in IDC evidence an association between SPOCK1 and EMT.}, } @article {pmid27625208, year = {2016}, author = {Hidalgo, IH and Fleming, T and Eckstein, V and Herzig, S and Nawroth, PP and Tyedmers, J}, title = {Characterization of aggregate load and pattern in living yeast cells by flow cytometry.}, journal = {BioTechniques}, volume = {61}, number = {3}, pages = {137-148}, doi = {10.2144/000114452}, pmid = {27625208}, issn = {1940-9818}, mesh = {Flow Cytometry/*methods ; Green Fluorescent Proteins/analysis/chemistry/genetics/metabolism ; High-Throughput Screening Assays ; Peptide Termination Factors/analysis/chemistry/genetics/metabolism ; *Protein Aggregates ; Recombinant Fusion Proteins/analysis/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*chemistry/cytology/metabolism ; Saccharomyces cerevisiae Proteins/analysis/chemistry/genetics/metabolism ; }, abstract = {Protein aggregation is both a hallmark of and a driving force for a number of diseases. It is therefore important to identify the nature of these aggregates and the mechanism(s) by which the cell counteracts their detrimental properties. Currently, the study of aggregation in vivo is performed primarily using fluorescently tagged versions of proteins and analyzing the aggregates by fluorescence microscopy. While this strategy is considered the gold standard, it has several limitations, particularly with respect to its suitability for high-throughput screening (HTS). Here, using a GFP fusion of the well-characterized yeast prion amyloid protein [PSI+], we demonstrate that flow cytometry, which utilizes the same physical principles as fluorescence microscopy, can be used to determine the aggregate load and pattern in live and fixed yeast cells. Furthermore, our approach can easily be applied to high-throughput analyses such as screenings with a yeast deletion library.}, } @article {pmid27616890, year = {2016}, author = {Song, XY and Li, BY and Zhou, EX and Wu, FX}, title = {The clinicopathological significance of RUNX3 hypermethylation and mRNA expression in human breast cancer, a meta-analysis.}, journal = {OncoTargets and therapy}, volume = {9}, number = {}, pages = {5339-5347}, pmid = {27616890}, issn = {1178-6930}, abstract = {Aberrant promoter methylation of RUNX3 has been reported in several tumors including human breast cancer (BC). However, the association between RUNX3 hypermethylation and incidence of BC remains elusive. In this study, a detailed literature search was performed in Medline and Google Scholar for related research publications. Analysis of pooled data were executed. Odds ratios with corresponding confidence intervals were determined and summarized, respectively. Finally, 13 studies were identified for the meta-analysis. Analysis of the pooled data showed that RUNX3 hypermethylation was significantly higher in both ductal carcinoma in situ and invasive ductal carcinoma (IDC) than in normal breast tissues. In addition, RUNX3 methylation was significantly higher in IDC than in benign tumor. However, RUNX3 methylation was not significantly higher in IDC than in ductal carcinoma in situ. We also determined that RUNX3 hypermethylation was significantly higher in ER positive BC than in ER negative BC. In addition, high RUNX3 mRNA expression was found to be correlated with better overall survival and relapse-free survival for all BC patients. Our results strongly support that RUNX3 hypermethylation may play an important role in BC incidence. RUNX3 methylation is a valuable early biomarker for the diagnosis of BC. Further large-scale studies will provide more insight into the role of RUNX3 hypermethylation in the carcinogenesis and clinical diagnosis of BC patients.}, } @article {pmid27616074, year = {2018}, author = {Chudiwal, SS and Dehghan, MHG}, title = {Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray.}, journal = {Pharmaceutical development and technology}, volume = {23}, number = {10}, pages = {1077-1087}, doi = {10.1080/10837450.2016.1236130}, pmid = {27616074}, issn = {1097-9867}, mesh = {Algorithms ; Anti-Asthmatic Agents/*administration & dosage/chemistry ; Anti-Inflammatory Agents/*administration & dosage/chemistry ; Drug Compounding ; Drug Liberation ; Excipients/chemistry ; Fluocinolone Acetonide/administration & dosage/*analogs & derivatives/chemistry ; Models, Chemical ; *Nasal Sprays ; Particle Size ; Polyethylene Glycols/chemistry ; Propylene Glycol/chemistry ; Viscosity ; }, abstract = {The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) (Y1) and D50 droplet size distribution (DSD) (μm) (Y2) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett-Burman and Box-Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) (Y1) was significantly impacted by formulation variables X1: propylene glycol (PG) (%) and X2: polyethylene glycol (PEG) 3350 (%), while D50 DSD (μm) (Y2) was significantly impacted by formulation variables X1: PG (%), X2: PEG 3350 (%) and device variable X8: delivery volume (μl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.}, } @article {pmid27614340, year = {2016}, author = {Sule, EA}, title = {T2 breast cancer presenting with diffuse liver metastases and hepatic failure following fertility treatment. Cautionary report.}, journal = {International journal of surgery case reports}, volume = {27}, number = {}, pages = {152-154}, pmid = {27614340}, issn = {2210-2612}, abstract = {BACKGROUND: Diffuse hepatic metastases with hepatic failure as a presentation of a T2 breast cancer is rare. This is also remarkable seeing our case had been on fertility treatments before presentation. There are no documented reports of breast cancer patient on fertility treatment presenting with diffuse hepatic metastases and liver failure.

CASE SUMMARY: A 41 year old Para 1 Nigerian woman being managed for secondary infertility with an extended use of clomiphene presented with a 3 months history of a left breast lump, nipple bleeding and later, yellowness of eyes, right hypochondrial pain malaise and drowsiness. Abdominal USS showed an enlarged liver with diffuse metastatic nodules. Liver function tests showed persistently elevating liver enzymes and serum bilirubin. Serology showed Hepatitis B negative. She was diagnosed with a T2 left invasive ductal carcinoma, Er-, Pr+ Her2+ with deteriorating liver function from diffuse hepatic metastases She had chemotherapy but succumbed barely a week of presentation.

CONCLUSION: Breast cancer screening for patients before fertility treatments and continual surveillance while on such treatment is highly recommended.}, } @article {pmid27612172, year = {2017}, author = {Katz, B and Raker, C and Edmonson, D and Gass, J and Stuckey, A and Rizack, T}, title = {Predicting Breast Tumor Size for Pre-operative Planning: Which Imaging Modality is Best?.}, journal = {The breast journal}, volume = {23}, number = {1}, pages = {52-58}, doi = {10.1111/tbj.12680}, pmid = {27612172}, issn = {1524-4741}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Carcinoma, Lobular/diagnostic imaging/pathology ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Mammography ; Middle Aged ; Preoperative Care ; Ultrasonography, Mammary ; }, abstract = {We sought to compare breast tumor size predicted by imaging modality to the actual pathologic size in order to determine which imaging modality is best at estimating tumor size. We identified 261 patients with biopsy-proven invasive ductal (IDC) and/or invasive lobular (ILC) carcinomas with documented tumor dimensions predicted by imaging and maximum dimensions determined by final pathology. Results of imaging-predicted dimension were correlated with final pathological size. Spearman correlations were calculated and compared by Zou's method and agreement was assessed by McNemar's test. There was no significant difference (p > 0.05) between correlations of pathologic size by ultrasound (r = 0.71) and magnetic resonance imaging (MRI) (0.76). The correlations between MRI or ultrasound and pathologic size are significantly stronger than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05). MRI and ultrasound are both strongly correlated with pathologic size overall and within grades in both IDC and ILC. The correlations between MRI or ultrasound and pathologic size are significantly better than the correlations between mammography or clinical breast exam and pathologic size (p < 0.05).}, } @article {pmid27611215, year = {2016}, author = {Cheung, YC and Juan, YH and Lin, YC and Lo, YF and Tsai, HP and Ueng, SH and Chen, SC}, title = {Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI-RADS 4 Non-Mass Microcalcifications in Screened Women.}, journal = {PloS one}, volume = {11}, number = {9}, pages = {e0162740}, pmid = {27611215}, issn = {1932-6203}, mesh = {Aged ; Calcinosis/*diagnostic imaging ; Contrast Media/*chemistry ; Female ; Humans ; Mammography/*methods ; *Mass Screening ; Middle Aged ; ROC Curve ; }, abstract = {BACKGROUND: Mammography screening is a cost-efficient modality with high sensitivity for detecting impalpable cancer with microcalcifications, and results in reduced mortality rates. However, the probability of finding microcalcifications without associated cancerous masses varies. We retrospectively evaluated the diagnosis and cancer probability of the non-mass screened microcalcifications by dual-energy contrast-enhanced spectral mammography (DE-CESM).

PATIENTS AND METHODS: With ethical approval from our hospital, we enrolled the cases of DE-CESM for analysis under the following inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications; (2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by sonography and physical examination; and (4) pathology-based diagnosis using stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post-contrast enhancement on DE-CESM.

RESULTS: A total of 94 biopsed lesions were available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35 benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory (AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013) and higher cancer probability than the amorphous microcalcifications (46.3% VS 15.1%). The Odds Ratio was 4.85 (95% CI: 1.84-12.82).

CONCLUSION: DE-CESM might provide added value in assessing the non-mass screened breast microcalcification, with enhancement favorable to the diagnosis of cancers or lack of enhancement virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers.}, } @article {pmid27602781, year = {2017}, author = {Ribeiro, J and Figueiredo, P and Morais, S and Alves, F and Toussaint, H and Vilas-Boas, JP and Fernandes, RJ}, title = {Biomechanics, energetics and coordination during extreme swimming intensity: effect of performance level.}, journal = {Journal of sports sciences}, volume = {35}, number = {16}, pages = {1614-1621}, doi = {10.1080/02640414.2016.1227079}, pmid = {27602781}, issn = {1466-447X}, mesh = {Athletic Performance/*physiology ; Biomechanical Phenomena ; Energy Metabolism/physiology ; Humans ; Lactic Acid/blood ; Male ; Motor Skills/*physiology ; Oxygen Consumption/physiology ; Swimming/*physiology ; Time and Motion Studies ; Young Adult ; }, abstract = {The present study aimed to examine how high- and low-speed swimmers organise biomechanical, energetic and coordinative factors throughout extreme intensity swim. Sixteen swimmers (eight high- and eight low-speed) performed, in free condition, 100-m front crawl at maximal intensity and 25, 50 and 75-m bouts (at same pace as the previous 100-m), and 100-m maximal front crawl on the measuring active drag system (MAD-system). A 3D dual-media optoelectronic system was used to assess speed, stroke frequency, stroke length, propelling efficiency and index of coordination (IdC), with power assessed by MAD-system and energy cost by quantifying oxygen consumption plus blood lactate. Both groups presented a similar profile in speed, power output, stroke frequency, stroke length, propelling efficiency and energy cost along the effort, while a distinct coordination profile was observed (F(3, 42) = 3.59, P = 0.04). Speed, power, stroke frequency and propelling efficiency (not significant, only a tendency) were higher in high-speed swimmers, while stroke length and energy cost were similar between groups. Performing at extreme intensity led better level swimmers to achieve superior speed due to higher power and propelling efficiency, with consequent ability to swim at higher stroke frequencies. This imposes specific constraints, resulting in a distinct IdC magnitude and profile between groups.}, } @article {pmid27589880, year = {2017}, author = {Jay, AM and Hamame, AS and Dul, C and Wesen, C}, title = {Breast Cancer in a 19-Year-Old Female Adolescent Identified with Li-Fraumeni Syndrome.}, journal = {Journal of pediatric and adolescent gynecology}, volume = {30}, number = {1}, pages = {e5-e6}, doi = {10.1016/j.jpag.2016.08.011}, pmid = {27589880}, issn = {1873-4332}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Humans ; Li-Fraumeni Syndrome/*genetics ; *Tumor Suppressor Protein p53 ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is rare in adolescents. In one study, breast carcinoma accounted for 0.02% of breast masses surgically removed in young women. We report a case of breast cancer in a 19-year-old woman who was found to have Li-Fraumeni Syndrome.

CASE: The patient presented with a new, hard, nonmobile lump in the right breast which prompted her to seek medical attention. A biopsy identified invasive ductal carcinoma. Genetic testing showed a p53 mutation associated with Li-Fraumeni syndrome.

SUMMARY AND CONCLUSION: Although breast masses in young women are mostly benign, one must entertain the possibility of more serious conditions when a breast mass is identified with concerning medical or physical findings. Genetic testing might be informative for such patients.}, } @article {pmid27588192, year = {2016}, author = {Hisada, T and Sawaki, M and Ishiguro, J and Adachi, Y and Kotani, H and Yoshimura, A and Hattori, M and Yatabe, Y and Iwata, H}, title = {Impact of intraoperative specimen mammography on margins in breast-conserving surgery.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {3}, pages = {269-272}, pmid = {27588192}, issn = {2049-9450}, abstract = {A positive resection margin is one of the most significant risk factors for local breast cancer recurrence following breast-conserving surgery (BCS). Intraoperative specimen mammography (SMMG) is routinely used to evaluate the surgical margin at our institution. The aim of the present study was to assess the adequacy of SMMG for margin assessment. The patient cohort included 174 women who underwent BCS in 2006. The sensitivity and specificity of SMMG were assessed by comparing the margins assessed by histological and radiological methods. It was also examined whether the rate of positive histological margins was decreased by re-excision following SMMG evaluation. A total of 23 false-negatives and 6 false-positives were determined by SMMG. The sensitivity and specificity of SMMG margin assessment for patients with primary breast cancer were 20.6 and 94.6%, respectively. The positive predictive value was 50% and the negative predictive value was 82.2%. A subgroup analysis revealed that the sensitivity and specificity of SMMG in cases with ductal carcinoma in situ (DCIS) were higher compared with those in invasive ductal carcinoma. Furthermore, the positive histological margin rate was not affected by re-excision. Although the general usefulness of intraoperative SMMG was not proven, this procedure may be useful in specific cases, particularly those with DCIS and those diagnosed by stereotactic biopsy. A prospective study with exact criteria and a standard procedure is required.}, } @article {pmid29518302, year = {2016}, author = {Baillie, J}, title = {BIM and its benefits explained.}, journal = {Health estate}, volume = {70}, number = {8}, pages = {19-22}, pmid = {29518302}, mesh = {*Computer-Aided Design ; Congresses as Topic ; *Hospital Design and Construction ; *Maintenance and Engineering, Hospital ; United Kingdom ; }, abstract = {A high-level look at Building Information Modelling's key benefits, the potential pitfalls, and the priorities for successful implementation, in the wake of the recent Government mandate that all centrally procured public sector construction projects commenced after 4 April this year be implementing BIM Level 2, was given by Chartered Quantity Surveyor, Gary Allen, of IDC-Consult, at the first in a series of planned IHEEM/HefmA joint seminars on the topic held recently at the headquarters of the Royal Institution of Chartered Surveyors (RICS) in London. HEJ editor, Jonathan Baillie, reports.}, } @article {pmid27578393, year = {2016}, author = {Koike, E and Iwaya, K and Watanabe, A and Miyake, S and Sato, E and Ishikawa, T}, title = {Association between Breast Cancer Recurrence and Cellular Dissociation Assessed Using Fine-Needle Aspiration.}, journal = {Acta cytologica}, volume = {60}, number = {5}, pages = {413-420}, doi = {10.1159/000448508}, pmid = {27578393}, issn = {1938-2650}, mesh = {Actin-Related Protein 2/metabolism ; Biopsy, Fine-Needle/methods ; Breast Neoplasms/metabolism/*pathology ; Cadherins/metabolism ; Female ; Humans ; Mastectomy, Radical/methods ; Multivariate Analysis ; Neoplasm Recurrence, Local/metabolism/*pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; Wiskott-Aldrich Syndrome Protein Family/metabolism ; }, abstract = {OBJECTIVE: To determine the associations between breast cancer recurrence and cytological findings of fine-needle aspiration cytology (FNAC).

STUDY DESIGN: The study included 117 women who had undergone a modified radical mastectomy for invasive ductal carcinoma of the breast. FNAC samples of these patients were reexamined, and cytological findings, such as cellular dissociation, nuclear pleomorphism, nuclear atypia, chromatin pattern, and nuclear size, were scored. Uni- and multivariate analyses were performed to determine the prognostic significance of the cytological findings. Corresponding cancer tissues were immunostained for estrogen receptor, progesterone receptor, human epidermal growth factor 2 (HER2), p53, and E-cadherin to determine their associations with cytological findings. Coexpression of Arp2 and WAVE2 was also examined immunohistochemically as a cell locomotion signal.

RESULTS: Cellular dissociation (p = 0.0259) and nuclear size (p = 0.0417) were significantly associated with cancer recurrence. Multivariate analysis showed that cellular dissociation and histological grade were significant independent predictors of cancer recurrence. Cellular dissociation was found to be associated with coexpression of Arp2 and WAVE2 (p = 0.0356) and HER2 (p = 0.0469).

CONCLUSION: The cytological finding of cell dissociation was associated with the activation of Arp2 and WAVE2 signals and was an independent predictor of recurrence.}, } @article {pmid27576528, year = {2016}, author = {Calhoun, BC and Portier, B and Wang, Z and Minca, EC and Budd, GT and Lanigan, C and Tubbs, RR and Morrison, LE}, title = {MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {695}, pmid = {27576528}, issn = {1471-2407}, mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Area Under Curve ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology ; Chemotherapy, Adjuvant/methods ; Female ; Gene Dosage ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ki-67 Antigen/biosynthesis ; Middle Aged ; Neoadjuvant Therapy/methods ; PTEN Phosphohydrolase/genetics ; Prognosis ; Proto-Oncogene Proteins c-met/genetics ; ROC Curve ; Receptor, ErbB-2 ; Sensitivity and Specificity ; Trastuzumab/*therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment.

METHODS: Biopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated.

RESULTS: Of the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC = 0.791, sensitivity = 92 % and specificity = 67 % at optimal cutoff, p = 0.0032) and gain of PTEN (AUC = 0.674, sensitivity = 38 % and specificity = 100 % at optimal cutoff, p = 0.039). Ki-67 expression was also found to associate significantly with pCR (AUC = 0.726, sensitivity = 100 % and specificity = 42 % at optimal cutoff, p = 0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC = 0.847, sensitivity = 92 % and specificity = 83 % at optimal cutoffs, p = 0.0006).

CONCLUSIONS: An immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.}, } @article {pmid27571348, year = {2016}, author = {Rohm, M and Schäfer, M and Laurent, V and Üstünel, BE and Niopek, K and Algire, C and Hautzinger, O and Sijmonsma, TP and Zota, A and Medrikova, D and Pellegata, NS and Ryden, M and Kulyte, A and Dahlman, I and Arner, P and Petrovic, N and Cannon, B and Amri, EZ and Kemp, BE and Steinberg, GR and Janovska, P and Kopecky, J and Wolfrum, C and Blüher, M and Berriel Diaz, M and Herzig, S}, title = {An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice.}, journal = {Nature medicine}, volume = {22}, number = {10}, pages = {1120-1130}, pmid = {27571348}, issn = {1546-170X}, mesh = {AMP-Activated Protein Kinases/*metabolism/pharmacology ; Adipocytes, White/*drug effects/metabolism ; Adipose Tissue, White/*drug effects/metabolism ; Animals ; Apoptosis Regulatory Proteins/*drug effects/metabolism ; Cachexia/etiology/*metabolism ; Cells, Cultured ; In Vitro Techniques ; Lipid Metabolism/*drug effects ; Lipogenesis/drug effects ; Lipolysis/drug effects ; Mice ; Neoplasms/complications/*metabolism ; Peptide Fragments/*pharmacology ; Thermogenesis/drug effects ; Uncoupling Protein 1/drug effects/metabolism ; }, abstract = {Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.}, } @article {pmid27571158, year = {2016}, author = {Barone, P and Santangelo, G and Amboni, M and Pellecchia, MT and Vitale, C}, title = {Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment.}, journal = {The Lancet. Neurology}, volume = {15}, number = {10}, pages = {1063-1074}, doi = {10.1016/S1474-4422(16)30173-9}, pmid = {27571158}, issn = {1474-4465}, mesh = {Aged ; Aged, 80 and over ; *Dystonia/etiology/physiopathology/therapy ; Female ; Humans ; Male ; Middle Aged ; Parkinsonian Disorders/*complications ; *Spinal Curvatures/etiology/physiopathology/therapy ; }, abstract = {Pisa syndrome is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. It is a frequent and often disabling complication of Parkinson's disease, and has also been described in several atypical forms of parkinsonism and in neurodegenerative and psychiatric disorders after drug exposure and surgical procedures. Although no consistent diagnostic criteria for Pisa syndrome are available, most investigations have adopted an arbitrary cutoff of at least 10° of lateral flexion for the diagnosis of the syndrome. Pathophysiological mechanisms underlying Pisa syndrome have not been fully explained. One hypothesis emphasises central mechanisms, whereby Pisa syndrome is thought to be caused by alterations in sensory-motor integration pathways; by contrast, a peripheral hypothesis emphasises the role of anatomical changes in the musculoskeletal system. Furthermore, several drugs are reported to induce Pisa syndrome, including antiparkinsonian drugs. As Pisa syndrome might be reversible, clinicians need to be able to recognise this condition early to enable prompt management. Nevertheless, further research is needed to determine optimum treatment strategies.}, } @article {pmid27569097, year = {2016}, author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, A and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoghli, T and Bouassida, J and Harzallah, L and Guemira, F}, title = {MDM2 344T>A polymorphism; could it be a predictive marker of anthracycline resistance?.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {3}, pages = {732-739}, pmid = {27569097}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Drug Resistance, Neoplasm ; Female ; Genes, p53 ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-mdm2/*genetics ; }, abstract = {PURPOSE: To find a possible association between the Mouse Double Minute 2(MDM2) 344T>A, alone and in combination with p53 72 Arg/Pro polymorphism, and resistance to anthracycline-based chemotherapy of breast cancer in Tunisia.

METHODS: This study enrolled 542 patients with invasive ductal carcinoma (IDC) treated with anthracycline-based chemotherapy. Genomic DNA was isolated from whole blood, using the phenol chloroform method. Anthracycline response was scored according to the World Health Organization (WHO). MDM2 344T>A polymorphism was genotyped using real time polymerase chain reaction (RT-PCR) with the TaqMan method. Data was statistically analyzed using the x2 test.

RESULTS: Response was evaluated in 400 patients, of whom a quarter was found to be resistant to chemotherapy. Genetic data revealed that resistance to anthracycline-based chemotherapy did not seem to be correlated with 344T>A polymorphism in the studied population. Also, no significant association was found between the single nucleotide polymorphism (SNP) 344T>A status and clinicopathologic parameters (p>0.05 for all comparisons). Moreover, analysis of p53 rs1042522 and MDM2 rs1196333 combination showed no significant association between these two genetic variants and anthracycline resistance (p=0.2).

CONCLUSIONS: Our findings provide no evidence indicating that SNP 344 T>A may affect response to anthracycline-based chemotherapy. However, the results obtained from the combination of SNPs 344T>A of MDM2 and 72 Arg/Pro of p53, do not support the hypothesis of the prominent role of common p53 and MDM2 variations in the genetic mechanisms of chemotherapy resistance in breast cancer.}, } @article {pmid27569075, year = {2016}, author = {Altundag, K and Isik, M and Sever, AR}, title = {Handedness and breast cancer characteristics.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {21}, number = {3}, pages = {576-579}, pmid = {27569075}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*mortality/pathology ; Female ; *Functional Laterality ; Humans ; Male ; Middle Aged ; }, abstract = {PURPOSE: Around 10% of the population is left-handed (LH) and the new data suggests that there is genetic as well as environmental influence on the hand preference. The purpose of this study was to evaluate the relationship between breast cancer and hand preference.

METHODS: Breast cancer patients diagnosed and treated at the Department of Medical Oncology, Hacettepe University, Institute of Oncology between March 2006 and May 2010 were included in the study. The preferred handedness was asked in all patients and recorded in the patients' medical database.

RESULTS: A total of 898 patients with breast cancer were analyzed for handedness, basic characteristics and survival. The median age was 48 years (range 20-83) and all but one patient were female. Of all, 434 (48.3%) patients were pre, 61 (6.8%) were peri, and 399 patients (44.4%) were postmenopausal. Nearly all of the patients (n=869, 96.7%) were operated and modified radical mastectomy was the most frequent type of surgery (N=654, 72.8%). Invasive ductal carcinoma was observed in 659 (73.3%) and in 659 patients (73.1%)estrogen receptors (ER) were positive. Similarly 569 (63.4 %) patients were progesterone receptor (PR) positive and 181 (20.2%) had HER2 overexpression. Most of the patients had T2 (434; 48.3%), N0 (376; 41.9%) and M0 (830; 92.4%) tumors. Of all, 55 (6.1%) patients were LH and the remaining 843 (93.9%) were right-handed (RH). There was no statistically significant difference between the groups related to ER or PR status, TNM classification, tumor localization, menopausal status, HER2 or histological subtype. However the median age of diagnosis in right-handers was higher (48-46 years, p=0.02). There were 10 (1.1%) patients who had already passed away at the time of analysis. The mean overall survival (OS) for RH patients was 33 months (range 1-281) and for LH patients it was 35 months (range 1-182) (p=0.751). The disease disease-free survival (DFS) was 29 months for both groups (p=1.00).

CONCLUSION: In our trial the onset of breast cancer was 2 years earlier in LH patients with similar disease characteristics compared to RH patients. As a consequence, it may be advocated that the screening of LH patients should start earlier.}, } @article {pmid27566960, year = {2016}, author = {Choi, WJ and Cha, JH and Kim, HH and Shin, HJ and Chae, EY}, title = {The Accuracy of Breast MR Imaging for Measuring the Size of a Breast Cancer: Analysis of the Histopathologic Factors.}, journal = {Clinical breast cancer}, volume = {16}, number = {6}, pages = {e145-e152}, doi = {10.1016/j.clbc.2016.07.007}, pmid = {27566960}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Contrast Media ; *Dimensional Measurement Accuracy ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/methods ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: The objective of the study was to compare the accuracy of different magnetic resonance (MR) sequences for measuring tumor size and to evaluate whether the imaging and histopathologic features affect the accuracy of the tumor size estimation on the MR sequence.

PATIENTS AND METHODS: Eight hundred women were included. The maximum diameter of the tumor was measured on T2-weighted (T2W) sequences, early-subtracted dynamic contrast-enhanced (DCE) T1-weighted (T1W) sequences, and maximal intensity projection (MIP) reconstructions. Agreement between the MR imaging and pathology-determined size were analyzed. Using the best MR sequence to measure the tumor size, the relationship between the accuracy and the imaging and histopathologic features were evaluated.

RESULTS: Tumor measurement showed a good agreement with the pathology-determined size, and with the best results using MIP (k = 0.805) compared with the early-subtracted DCE T1W sequence (k = 0.802) and the T2W sequence (k = 0.779). On MIP, the tumors of patients with minimal or mild background parenchymal enhancement, a mass, invasive ductal carcinoma (IDC), pathology-determined size < 2 cm, positive estrogen receptor, negative HER2, luminal A type, nuclear and histologic grade 1, negative nodal status, negative lymphovascular invasion, and negative extensive intraductal component were significantly more accurately estimated. The independent factors associated with the accuracy of tumor measurement were a mass, IDC, and the pathology-determined size < 2 cm.

CONCLUSION: Our study showed that tumor size is most accurately measured on MIP, especially for IDC appearing as a mass on MR imaging and with the pathology-determined size < 2 cm.}, } @article {pmid27563488, year = {2016}, author = {Janowczyk, A and Madabhushi, A}, title = {Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases.}, journal = {Journal of pathology informatics}, volume = {7}, number = {}, pages = {29}, pmid = {27563488}, issn = {2229-5089}, support = {R01 CA202752/CA/NCI NIH HHS/United States ; R21 CA179327/CA/NCI NIH HHS/United States ; R21 CA195152/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Deep learning (DL) is a representation learning approach ideally suited for image analysis challenges in digital pathology (DP). The variety of image analysis tasks in the context of DP includes detection and counting (e.g., mitotic events), segmentation (e.g., nuclei), and tissue classification (e.g., cancerous vs. non-cancerous). Unfortunately, issues with slide preparation, variations in staining and scanning across sites, and vendor platforms, as well as biological variance, such as the presentation of different grades of disease, make these image analysis tasks particularly challenging. Traditional approaches, wherein domain-specific cues are manually identified and developed into task-specific "handcrafted" features, can require extensive tuning to accommodate these variances. However, DL takes a more domain agnostic approach combining both feature discovery and implementation to maximally discriminate between the classes of interest. While DL approaches have performed well in a few DP related image analysis tasks, such as detection and tissue classification, the currently available open source tools and tutorials do not provide guidance on challenges such as (a) selecting appropriate magnification, (b) managing errors in annotations in the training (or learning) dataset, and (c) identifying a suitable training set containing information rich exemplars. These foundational concepts, which are needed to successfully translate the DL paradigm to DP tasks, are non-trivial for (i) DL experts with minimal digital histology experience, and (ii) DP and image processing experts with minimal DL experience, to derive on their own, thus meriting a dedicated tutorial.

AIMS: This paper investigates these concepts through seven unique DP tasks as use cases to elucidate techniques needed to produce comparable, and in many cases, superior to results from the state-of-the-art hand-crafted feature-based classification approaches.

RESULTS: Specifically, in this tutorial on DL for DP image analysis, we show how an open source framework (Caffe), with a singular network architecture, can be used to address: (a) nuclei segmentation (F-score of 0.83 across 12,000 nuclei), (b) epithelium segmentation (F-score of 0.84 across 1735 regions), (c) tubule segmentation (F-score of 0.83 from 795 tubules), (d) lymphocyte detection (F-score of 0.90 across 3064 lymphocytes), (e) mitosis detection (F-score of 0.53 across 550 mitotic events), (f) invasive ductal carcinoma detection (F-score of 0.7648 on 50 k testing patches), and (g) lymphoma classification (classification accuracy of 0.97 across 374 images).

CONCLUSION: This paper represents the largest comprehensive study of DL approaches in DP to date, with over 1200 DP images used during evaluation. The supplemental online material that accompanies this paper consists of step-by-step instructions for the usage of the supplied source code, trained models, and input data.}, } @article {pmid27563478, year = {2016}, author = {Tabai, M and Hazboun, IM and Sakuma, ET and Sampaio, MH and Sakano, E}, title = {Orbital Metastasis of Breast Cancer Mimicking Invasive Fungal Rhinosinusitis.}, journal = {Case reports in otolaryngology}, volume = {2016}, number = {}, pages = {2913241}, pmid = {27563478}, issn = {2090-6765}, abstract = {Introduction. A range of traumatic, vascular, inflammatory, infectious, and neoplastic processes can affect the orbit and its structures. In the area of otolaryngology, the rhino-orbital-cerebral involvement of invasive fungal rhinosinusitis can affect the orbit, which may look like initially a rhinosinusitis or even mimic malignancy. Case Presentation. Female patient, 32 years old, with headache and ocular proptosis. She was using prednisone in immunosuppressive doses for a year and had breast cancer treated three years earlier. The initial CT scan showed opacification of the sphenoid and ethmoid sinuses, left intraorbital involvement and contrast impregnation in the cavernous sinus. The biopsy resulted positive for invasive ductal carcinoma of the breast. Discussion. The initial CT scan of our patient showed both signs of early changes of invasive fungal rhinosinusitis (IFR) and possible metastatic involvement. The intracranial extension and ocular involvement are usually the most common signs of IFR (first hypothesis). Among metastases at the orbit and the eye, breast and lung carcinomas are the most frequent. Conclusion. Although several studies on the differential diagnosis of orbital lesions exist, especially when it concerns the involvement of the nasal cavity, the diagnosis by imaging is still a challenge.}, } @article {pmid27562577, year = {2016}, author = {Regan, JP and Casaubon, JT and Genelus-Dominique, E}, title = {Synchronous invasive ductal carcinoma in encapsulated papillary ductal carcinoma.}, journal = {Journal of surgical case reports}, volume = {2016}, number = {8}, pages = {}, pmid = {27562577}, issn = {2042-8812}, abstract = {Encapsulated papillary ductal carcinoma (EPC) of the breast is a rare form of cancer with defining histopathology of encapsulation. These lesions are typically indolent but may rarely have concomitant, synchronous invasive lesions.This report details a 56-year-old black female who presented with a palpable left breast mass. Adenosis with focal fibrous and ductal hyperplasia characteristics were found on core needle biopsy. Excisional biopsy showed EPC with invasive components. A simple mastectomy was performed and a second lesion was identified as invasive ductal carcinoma.EPC typically has good prognosis and a low incidence of invasion. The risk increases in the presence of a second, synchronous lesion as in our case. Management is typically performed with breast conserving methods; however, missing a second lesion is possible. This report provides an overview of the literature and discussion of the role of MRI in preoperative workup.}, } @article {pmid27562390, year = {2016}, author = {Şener, E and Şipal, S and Gündoğdu, C}, title = {Comparison of Microvessel Density with Prognostic Factors in Invasive Ductal Carcinomas of the Breast.}, journal = {Turk patoloji dergisi}, volume = {32}, number = {3}, pages = {164-170}, doi = {10.5146/tjpath.2016.01366}, pmid = {27562390}, issn = {1309-5730}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/*pathology ; Carcinoma, Ductal, Breast/blood supply/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Microvessels/pathology ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic/*pathology ; Prognosis ; }, abstract = {OBJECTIVE: Angiogenesis plays a key role in tumor growth and metastasis. Determination of microvessel density is the most common technique used to evaluate the amount of the intratumoral angiogenesis in breast cancer. We have aimed to investigate the relationship with tumor angiogenesis and prognostic parameters in breast invasive ductal carcinomas.

MATERIAL AND METHOD: In this study, a total of 100 invasive ductal carcinoma patients, who were diagnosed at the Department of Pathology, Ataturk University Faculty of Medicine between the years 2003-2008, were re-evaluated. Patient characteristics and clinicopathological findings were obtained from archival records. In the present study, microvessel density was determined by immunohistochemical staining by using anti-CD34 monoclonal antibody in the paraffin blocks. First, the most vascular area was selected in the tumor under a low magnification (40x) by a light microscope and then microvessels were counted under a higher magnification (200x). Patients were classified as low and high microvessel density depending on their microvessel counts. Chi-square test and multivariate linear regression analysis were used for statistical analysis (p≤0.05).

RESULTS: We have determined that microvessel density increases as tumor size increases (p=0.001). Microvessel density was higher in patients with at least 10 lymph node metastases compared to those with no metastasis (p=0.05). However, there was no statistically significant difference between microvessel density and other prognostic factors such as histological grade, nuclear grade, patient age, vascular invasion, estrogen, progesterone receptor status, HER2/neu expression.

CONCLUSION: In our study, we have found that microvessel density is associated with tumor size and lymph node metastasis in patients with invasive ductal carcinoma.}, } @article {pmid27562113, year = {2016}, author = {Li, Z and Liu, Q and Piao, J and Hua, F and Wang, J and Jin, G and Lin, Z and Zhang, Y}, title = {Clinicopathological implications of Tiam1 overexpression in invasive ductal carcinoma of the breast.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {681}, pmid = {27562113}, issn = {1471-2407}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Guanine Nucleotide Exchange Factors/*genetics/metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; }, abstract = {BACKGROUND: T-lymphoma invasion and metastasis-inducing protein 1 (Tiam1) has been implicated in tumor occurrence and progression. Recent studies have shown that high expression levels of Tiam1 protein appear to be associated with the progression of numerous human tumors. This study attempted to explore the role of Tiam1 protein in tumor progression and the prognostic evaluation of breast cancer.

METHODS: The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining. In addition, a total of 283 breast tissue samples, including 153 breast cancer tissues, 67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues, were analyzed by immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics was evaluated by Chi-square test and Fisher's exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were performed by the Cox proportional hazards regression models.

RESULTS: Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells; however, nuclear staining was also observed. Tiam1 protein expression was significantly higher in breast cancers (42.5 %, 65/153) and DCIS (40.3 %, 27/67) than in adjacent non-tumor tissues (12.7 %, 8/63). In addition, Tiam1 associated with tumor stage and Ki-67 expression, but negatively correlated with receptor tyrosine-protein kinase erbB-2 (Her2) expression. Moreover, survival analyses showed that DFS and 10-year OS rates were significantly lower in breast cancer patients with high Tiam1 expression than those with low Tiam1 expression. Univariate analysis suggested that molecular types, clinical stage, Her2 expression levels and Tiam1 expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients. Furthermore, multivariate analysis suggested that Tiam1 expression is a significant independent prognostic factor along with tumor stage in patients with breast cancer.

CONCLUSIONS: Tiam1 expression is frequently up-regulated in breast cancer. Tiam1 expression correlated with clinicopathological parameters, suggesting that it may be a useful prognostic biomarker and potential therapeutic target for patients with breast cancer.}, } @article {pmid27561329, year = {2016}, author = {Zagelbaum, NK and Ward, MF and Okby, N and Karpoff, H}, title = {Invasive ductal carcinoma of the breast with osteoclast-like giant cells and clear cell features: a case report of a novel finding and review of the literature.}, journal = {World journal of surgical oncology}, volume = {14}, number = {1}, pages = {227}, pmid = {27561329}, issn = {1477-7819}, mesh = {Biopsy, Large-Core Needle ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/*pathology ; Female ; Giant Cells/*pathology ; Humans ; Image-Guided Biopsy ; Immunohistochemistry ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Osteoclasts/*pathology ; Prognosis ; Rare Diseases/diagnosis/diagnostic imaging/pathology ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Osteoclast-like giant cells (OLGCs) are a rare histologic finding within a tumor of the breast. Although there has been discussion as to the pathogenesis and prognosis related to this finding, our understanding of its significance remains inconclusive. Clear cells are another unique histologic finding in breast tumors and are typically associated with tumors arising in other organs such as renal cell carcinoma.

CASE PRESENTATION: This is a case report of a 64-year-old female who presented with one tumor identified as invasive ductal carcinoma with a combination of OLGCs and clear cell features.

CONCLUSIONS: To our knowledge, this combination of findings has not been previously described in the literature and therefore represents another morphologic manifestation of breast carcinoma. As patients are diagnosed earlier and live longer, a growing number of these rare variants may be recognized and provide opportunities to further our understanding of the associated molecular pathways which could contribute to the possibility of therapeutic intervention.}, } @article {pmid27559367, year = {2016}, author = {Kumar, N and Ghosh, S and Bhunia, S and Bisai, A}, title = {Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp(2) C-H and sp(3) C-H bonds.}, journal = {Beilstein journal of organic chemistry}, volume = {12}, number = {}, pages = {1153-1169}, pmid = {27559367}, issn = {1860-5397}, abstract = {The synthesis of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudo benzylic position has been achieved via a 'transition-metal-free' intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon-carbon bonds using KOt-Bu-catalyzed one pot C-alkylation of β-N-arylamido esters with alkyl halides followed by a dehydrogenative coupling. Experimental evidences indicated toward a radical-mediated path for this reaction.}, } @article {pmid27556047, year = {2016}, author = {Zhang, L and Xia, CQ}, title = {PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells.}, journal = {Journal of immunology research}, volume = {2016}, number = {}, pages = {2419621}, pmid = {27556047}, issn = {2314-7156}, mesh = {Adoptive Transfer ; Animals ; B7-H1 Antigen/*metabolism ; Graft Survival/immunology ; *Immune Tolerance/radiation effects ; Isoantigens/*immunology ; Lymphocyte Activation/immunology ; Mice ; Programmed Cell Death 1 Receptor/*metabolism ; Protein Binding ; Skin Transplantation ; T-Lymphocyte Subsets/immunology/metabolism ; *Ultraviolet Rays ; }, abstract = {Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti-PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD-1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens.}, } @article {pmid27550996, year = {2016}, author = {Zwack, PJ and De Clercq, I and Howton, TC and Hallmark, HT and Hurny, A and Keshishian, EA and Parish, AM and Benkova, E and Mukhtar, MS and Van Breusegem, F and Rashotte, AM}, title = {Cytokinin Response Factor 6 Represses Cytokinin-Associated Genes during Oxidative Stress.}, journal = {Plant physiology}, volume = {172}, number = {2}, pages = {1249-1258}, pmid = {27550996}, issn = {1532-2548}, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Chlorophyll/chemistry/metabolism ; Cytokinins/*metabolism ; Fluorescence ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects/*genetics ; Gene Ontology ; Hydrogen Peroxide/pharmacology ; Mutation ; Oxidants/pharmacology ; *Oxidative Stress ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Seedlings/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; Two-Hybrid System Techniques ; }, abstract = {Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response.}, } @article {pmid27549622, year = {2016}, author = {Takahashi, Y and Uruga, H and Fujii, T and Mochizuki, S and Hanada, S and Takaya, H and Miyamoto, A and Morokawa, N and Kurosaki, A and Kishi, K}, title = {Antemortem diagnosis of pulmonary tumor thrombotic microangiopathy in a patient with recurrent breast cancer: a case report.}, journal = {BMC cancer}, volume = {16}, number = {1}, pages = {666}, pmid = {27549622}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Humans ; Lung/pathology ; Neoplasm Recurrence, Local/drug therapy/pathology ; Receptor, ErbB-2/metabolism ; *Thrombotic Microangiopathies/diagnosis/diagnostic imaging/drug therapy ; Tomography, X-Ray Computed ; Trastuzumab/*therapeutic use ; }, abstract = {BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM), a rare complication of advanced cancer, is histologically characterized by tumor embolisms and fibrocellular intimal proliferation of small pulmonary arteries and arterioles. PTTM usually has an extremely poor prognosis, and antemortem diagnosis is very difficult.

CASE PRESENTATION: A 65-year-old woman with a 5-year history of clinical stage IIA (T2N0M0) invasive ductal carcinoma of the left breast was hospitalized for worsening shortness of breath, hemoptysis, and cough since 2 months. She had previously received neoadjuvant chemotherapy and left mastectomy. Because the cancer cells were positive for human epidermal growth factor receptor 2 (HER2), four cycles of trastuzumab had been administered as adjuvant chemotherapy. On admission, chest computed tomography (CT) showed peripheral consolidations in both the lower lobes and a mediastinal mass. Specimens obtained on video-assisted thoracoscopic surgical biopsy revealed tumor cell embolism, intimal fibrocellular proliferation of small arteries, fibrin thrombi, recanalization, and infarction in the left lower lobe, as well as metastasis to the mediastinal pleura. Immunohistochemical staining of the tumor cells revealed positivity for HER2, and a diagnosis of recurrent breast cancer with PTTM was made. Four cycles of trastuzumab resulted in rapid improvement of her symptoms and CT findings of peripheral consolidations and the mediastinal mass.

CONCLUSION: An antemortem diagnosis of PTTM was made in a patient with HER2-positive recurrent breast cancer. Trastuzumab was effective for not only breast cancer but also PTTM.}, } @article {pmid27540549, year = {2016}, author = {Martínez Casas, I and Amador Marchante, MA and Paduraru, M and Fabregues Olea, AI and Nolasco, A and Medina, JC}, title = {Thorax Trauma Severity Score: Is it reliable for Patient's Evaluation in a Secondary Level Hospital?.}, journal = {Bulletin of emergency and trauma}, volume = {4}, number = {3}, pages = {150-155}, pmid = {27540549}, issn = {2322-2522}, abstract = {OBJECTIVE: To determine the predictive and diagnostic value of thorax trauma severity score (TTSS) in a population of thoracic trauma patients admitted to a secondary level trauma center.

METHODS: A Retrospective analysis of patients admitted over a period of two years with IDC-9 codes related to thoracic trauma was undertaken. The association of TTSS with complications and mortality was evaluated. We also determined the predictive value of TTSS using receiver operating characteristic curve (ROC).

RESULTS: 238 patients with thoracic trauma, mostly middle-aged (62.2 ± 15 years), were included. The main mechanisms of injury were falls and traffic accidents. Thirty-three patients had important extra-thoracic injuries, but only 9 presented an ISS> 15. The average ISS was 3 ± 5; Morbidity was 2.5% and mortality was 2.1% as a result of thoracic injury and these patients had significantly higher TTSS values. Each score component was analyzed separately, showing significant association with complications and mortality. The area under the curve for TTSS was significant for predicting complications (0.848) and mortality (0.856) values. TTSS with a cut off value of 8 points had a sensitivity of 66% and specificity of 94% to predict complications and 80% sensitivity and 94% specificity for predicting mortality.

CONCLUSIONS: The TTSS is an appropriate and feasible tool to predict the development of complications or mortality in a population of mostly mild thoracic trauma.}, } @article {pmid27540428, year = {2016}, author = {Kim, SJ and Kim, SJ and Kim, IJ and Pak, K and Kim, BS and Shin, S}, title = {Factors Associated with (18)F-Fluorodeoxyglucose Uptake in T1 and T2 Invasive Ductal Carcinoma of the Breast.}, journal = {Nuclear medicine and molecular imaging}, volume = {50}, number = {3}, pages = {240-245}, pmid = {27540428}, issn = {1869-3474}, abstract = {PURPOSE: The objective of this study was to investigate the relationship between diversity of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake of primary tumor in positron emission tomography (PET) and various clinicopathologic factors in breast cancer of same pathologic T1, T2 stage.

METHODS: A total of 258 patients with invasive ductal breast cancer were enrolled in this study. All patients underwent (18)F-FDG PET-CT before surgery. Patients were divided into two groups according to tumor size based on the pathologic T stage, and maximum standardized uptake value (SUVmax) of 2.5, respectively.

RESULTS: On the univariate analysis, estrogen receptor (ER), tumor size, lymphovascular invasion, p53, pathologic N status (pN) and Nottingham tumor grade (NG) were associated with high SUVmax in T1 and T2 breast cancer. On the multivariate logistic regression, tumor size and NG remained significant variables dividing high and low SUVmax. In the T1 group, ER, p53 and NG were significantly associated with high SUVmax on the univariate analysis. In this group, p53 and NG remained significant variables for dividing high and low SUVmax on the multivariate logistic regression. In the T2 group, only NG was associated with high SUVmax on the univariate analysis.

CONCLUSIONS: NG showed an association with (18)F-FDG uptake in both T1 and T2 breast cancer independently; however, p53 in T1 breast cancer.}, } @article {pmid27539136, year = {2016}, author = {Esclovon, JW and Ponder, M and Aydin, N and Misra, S}, title = {Challenges of treating incidental synchronous bilateral breast cancer with differing tumour biology.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, pmid = {27539136}, issn = {1757-790X}, mesh = {Breast Carcinoma In Situ/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Incidental Findings ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {A 59-year-old woman with right breast mass was diagnosed with invasive ductal carcinoma (IDC). Workup consisted of bilateral diagnostic mammogram and ultrasound (US); both showed a right breast mass with normal left breast. Core biopsy showed IDC with estrogen receptor negative (ER-)/progesterone receptor negative (PR-) and HER2/neu positive receptor status. The patient underwent carboplatin-based chemotherapy with Herceptin. The mass completely resolved. The patient desired to proceed with bilateral total mastectomy with right sentinel lymph node biopsy (SLNB). Pathology showed complete resolution of the right-sided breast mass without malignancy in right SLN. Incidentally, IDC was found in the left breast specimen, which was ER+/PR+ and HER 2/neu negative. Tumour board consensus was to obtain a left axilla US with MRI in 6 months if the US was unremarkable. Biologically different synchronous bilateral breast cancer poses a difficult clinical challenge for management due to differing responses to treatment. Use of MRI may be a diagnostic option in women who choose contralateral prophylactic mastectomy.}, } @article {pmid27536182, year = {2016}, author = {Provencher, L and Hogue, JC and Desbiens, C and Poirier, B and Poirier, E and Boudreau, D and Joyal, M and Diorio, C and Duchesne, N and Chiquette, J}, title = {Is clinical breast examination important for breast cancer detection?.}, journal = {Current oncology (Toronto, Ont.)}, volume = {23}, number = {4}, pages = {e332-9}, pmid = {27536182}, issn = {1198-0052}, abstract = {BACKGROUND: Screening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases.

METHODS: This retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered "abnormal" in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d'orange, or ulcers.

RESULTS: During the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05).

CONCLUSIONS: A significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram.}, } @article {pmid27535065, year = {2017}, author = {ErEl, H and Meiran, N}, title = {A drop in performance on a fluid intelligence test due to instructed-rule mindset.}, journal = {Psychological research}, volume = {81}, number = {5}, pages = {901-909}, pmid = {27535065}, issn = {1430-2772}, mesh = {Educational Measurement/*methods ; Humans ; *Intelligence ; Intelligence Tests/*statistics & numerical data ; }, abstract = {A 'mindset' is a configuration of processing resources that are made available for the task at hand as well as their suitable tuning for carrying it out. Of special interest, remote-relation abstract mindsets are introduced by activities sharing only general control processes with the task. To test the effect of a remote-relation mindset on performance on a Fluid Intelligence test (Raven's Advanced Progressive Matrices, RAPM), we induced a mindset associated with little usage of executive processing by requiring participants to execute a well-defined classification rule 12 times, a manipulation known from previous work to drastically impair rule-generation performance and associated cognitive processes. In Experiment 1, this manipulation led to a drop in RAPM performance equivalent to 10.1 IQ points. No drop was observed in a General Knowledge task. In Experiment 2, a similar drop in RAPM performance was observed (equivalent to 7.9 and 9.2 IQ points) regardless if participants were pre-informed about the upcoming RAPM test. These results indicate strong (most likely, transient) adverse effects of a remote-relation mindset on test performance. They imply that although the trait of Fluid Intelligence has probably not changed, mindsets can severely distort estimates of this trait.}, } @article {pmid27533259, year = {2016}, author = {Gaui, EN and Klein, CH and Oliveira, GM}, title = {Proportional Mortality due to Heart Failure and Ischemic Heart Diseases in the Brazilian Regions from 2004 to 2011.}, journal = {Arquivos brasileiros de cardiologia}, volume = {107}, number = {3}, pages = {230-238}, pmid = {27533259}, issn = {1678-4170}, mesh = {Adolescent ; Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; Cause of Death ; Child ; Child, Preschool ; Chronic Disease ; Female ; Heart Failure/*mortality ; Humans ; Infant ; Male ; Middle Aged ; Myocardial Ischemia/*mortality ; Risk Factors ; Sex Distribution ; Sex Factors ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND:: Heart failure (HF) and ischemic heart diseases (IHD) are important causes of death in Brazil.

OBJECTIVE:: To assess proportional mortality (PM) due to HF and IHD as underlying causes stratified by sex and age groups in the Brazilian geoeconomic regions from 2004 to 2011.

METHODS:: Data from death certificates were obtained in the DATASUS site under the following International Statistical Classification of Diseases and Related Health Problems codes, 10th Revision: 1) from chapter IX: I20 to I24 for acute IHD, I25 for chronic IHD, and I50 for HF; and 2) from chapter XVIII, for ill-defined causes (IDC).

RESULTS:: Proportional mortality due to HF increased with age in both sexes and all regions, the highest percentages being found among elderly women. Among men, the highest percentages were observed in the West-Central region up to the ninth decade, but, among the eldest individuals, the highest percentages were identified in the Southern region. Among women, the regions did not differ up to the age group of 70-79 years, although the West-Central region took the lead from 50 to 79 years; however, from the age of 80 years on, the Southern region showed the highest PM due to HF. Proportional mortality due to acute IHD in all Brazilian regions and in both sexes increased up to the age group of 60-69 years, from which it decreased. Among men, the Southeastern region had the highest percentages in the age group of 50-59 years, while women had lower PM due to acute IHD than men in all regions. In both sexes, PM due to chronic IHD increased with age in the Southern and Southeastern regions, which did not happen in the others, while the Southern region had the highest rate of all regions for all age groups.

CONCLUSIONS:: Regional differences were more prominent at more advanced ages, especially when deaths due to IDC were excluded.

FUNDAMENTO:: Insuficiência cardíaca (IC) e doenças isquêmicas do coração (DIC) são importantes causas de morte no Brasil.

OBJETIVO:: Avaliar a mortalidade proporcional (MP) por IC e DIC, como causas básicas, estratificada por sexo e faixa etária nas regiões brasileiras de 2004 a 2011.

MÉTODOS:: As informações das declarações de óbito foram obtidas no site do DATASUS, codificadas conforme a Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde, 10ª Revisão: 1) do Capítulo IX: I20 a I24 para DIC aguda, I25 para DIC crônica, e I50 para IC; e 2) do Capítulo XVIII, para causas mal definidas (CMD).

RESULTADOS:: A MP por IC aumentou com a idade nos dois sexos e em todas as regiões, as mais altas porcentagens sendo encontradas entre as mulheres mais idosas. Entre os homens, as mais altas porcentagens foram observadas na região Centro-Oeste até a nona década; entre os mais idosos, porém, as mais altas porcentagens foram identificadas na região Sul. Entre as mulheres, as regiões não diferiram até a faixa etária de 70-79 anos, embora a região Centro-Oeste tenha liderado dos 50 aos 79 anos; entretanto, a partir dos 80 anos, a região Sul apresentou a mais alta MP por IC. Em todas as regiões brasileiras e nos dois sexos, a MP por DIC aguda aumentou até a faixa etária de 60-69 anos, a partir da qual diminuiu. Entre os homens, a região Sudeste apresentou as mais altas porcentagens na faixa etária de 50-59 anos, enquanto as mulheres tiveram menor MP por DIC aguda em comparação aos homens em todas as regiões. Nos dois sexos, a MP por DIC crônica aumentou com a idade nas regiões Sul e Sudeste, mas não nas demais, enquanto a região Sul apresentou a mais alta MP entre todas as regiões para todas as faixas etárias.

CONCLUSÕES:: Diferenças regionais foram mais marcantes nas idades mais avançadas, especialmente quando excluídas as mortes por CMD.}, } @article {pmid27531234, year = {2016}, author = {Erel, H and Levy, DA}, title = {Orienting of visual attention in aging.}, journal = {Neuroscience and biobehavioral reviews}, volume = {69}, number = {}, pages = {357-380}, doi = {10.1016/j.neubiorev.2016.08.010}, pmid = {27531234}, issn = {1873-7528}, mesh = {Activities of Daily Living ; *Attention ; Cues ; Humans ; *Orientation ; Reaction Time ; *Visual Perception ; }, abstract = {Changes in attention are among the most important cognitive shifts associated with aging, with implications for maintenance of vocational competencies, participation in social interactions, and successful execution of activities of daily living. An important facet of attention is orienting, the ability to selectively attend a location or modality and thereby engender perceptual augmentation. Orienting also involves shifting of the focus of attention in response to unanticipated salient events. Aging may impact orienting through a variety of neurocognitive mechanisms and the interactions between them. We review findings regarding factors that mediate the impact of aging on orienting, including overt vs. covert attending, exogenous vs. endogenous processes, orienting benefits vs. reorienting costs, cue-target onset asynchrony (SOA), post-orienting task factors, and stage of aging. We also consider aging-related changes in the brain substrates of orienting, including cortical and white matter integrity, laterality, connectivity, neuromodulatory functions, and compensatory activity. Taken together, these findings suggest that healthy aging impacts performance on orienting tasks less through direct effects than via interactions with additional cognitive processes.}, } @article {pmid27529423, year = {2016}, author = {Qin, C and Sun, Y and Dong, Y}, title = {A New Method for Identifying Essential Proteins Based on Network Topology Properties and Protein Complexes.}, journal = {PloS one}, volume = {11}, number = {8}, pages = {e0161042}, pmid = {27529423}, issn = {1932-6203}, mesh = {Computational Biology ; Protein Interaction Mapping/*methods ; Saccharomyces cerevisiae Proteins/*metabolism ; Statistics as Topic ; }, abstract = {Essential proteins are indispensable to the viability and reproduction of an organism. The identification of essential proteins is necessary not only for understanding the molecular mechanisms of cellular life but also for disease diagnosis, medical treatments and drug design. Many computational methods have been proposed for discovering essential proteins, but the precision of the prediction of essential proteins remains to be improved. In this paper, we propose a new method, LBCC, which is based on the combination of local density, betweenness centrality (BC) and in-degree centrality of complex (IDC). First, we introduce the common centrality measures; second, we propose the densities Den1(v) and Den2(v) of a node v to describe its local properties in the network; and finally, the combined strategy of Den1, Den2, BC and IDC is developed to improve the prediction precision. The experimental results demonstrate that LBCC outperforms traditional topological measures for predicting essential proteins, including degree centrality (DC), BC, subgraph centrality (SC), eigenvector centrality (EC), network centrality (NC), and the local average connectivity-based method (LAC). LBCC also improves the prediction precision by approximately 10 percent on the YMIPS and YMBD datasets compared to the most recently developed method, LIDC.}, } @article {pmid27529253, year = {2016}, author = {Foong, S and Sun, Z}, title = {High Accuracy Passive Magnetic Field-Based Localization for Feedback Control Using Principal Component Analysis.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {8}, pages = {}, pmid = {27529253}, issn = {1424-8220}, abstract = {In this paper, a novel magnetic field-based sensing system employing statistically optimized concurrent multiple sensor outputs for precise field-position association and localization is presented. This method capitalizes on the independence between simultaneous spatial field measurements at multiple locations to induce unique correspondences between field and position. This single-source-multi-sensor configuration is able to achieve accurate and precise localization and tracking of translational motion without contact over large travel distances for feedback control. Principal component analysis (PCA) is used as a pseudo-linear filter to optimally reduce the dimensions of the multi-sensor output space for computationally efficient field-position mapping with artificial neural networks (ANNs). Numerical simulations are employed to investigate the effects of geometric parameters and Gaussian noise corruption on PCA assisted ANN mapping performance. Using a 9-sensor network, the sensing accuracy and closed-loop tracking performance of the proposed optimal field-based sensing system is experimentally evaluated on a linear actuator with a significantly more expensive optical encoder as a comparison.}, } @article {pmid27521604, year = {2016}, author = {Lee, JH and Kim, JE and Kim, BG and Han, HH and Kang, S and Cho, NH}, title = {STAT3-induced WDR1 overexpression promotes breast cancer cell migration.}, journal = {Cellular signalling}, volume = {28}, number = {11}, pages = {1753-1760}, doi = {10.1016/j.cellsig.2016.08.006}, pmid = {27521604}, issn = {1873-3913}, mesh = {Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Line, Tumor ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; HEK293 Cells ; Humans ; Microfilament Proteins/genetics/*metabolism ; Neoplasm Invasiveness ; Promoter Regions, Genetic/genetics ; Protein Binding ; STAT3 Transcription Factor/*metabolism ; Survival Analysis ; Up-Regulation ; }, abstract = {WD repeat domain 1 (WDR1), a protein that assists cofilin-mediated actin filament disassembly, is overexpressed in the invading front of invasive ductal carcinoma (IDC), but its implication of overexpression and how to be regulated have not been studied. In our study, we demonstrated that STAT3 bound to the 5' upstream sequence (-1971 to -1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. The exogenous overexpression of WDR1 increased the migration of MDA-MB-231, which was attenuated by WDR1 knockdown. In the analysis of breast cancer patients, WDR1 overexpression was associated with a shorter distant metastasis-free survival (DMFS), more specifically in basal-like tumors.}, } @article {pmid27521488, year = {2016}, author = {Georgiou, GP and Provatopoulou, X and Kalogera, E and Siasos, G and Menenakos, E and Zografos, GC and Gounaris, A}, title = {Serum resistin is inversely related to breast cancer risk in premenopausal women.}, journal = {Breast (Edinburgh, Scotland)}, volume = {29}, number = {}, pages = {163-169}, doi = {10.1016/j.breast.2016.07.025}, pmid = {27521488}, issn = {1532-3080}, mesh = {Adiponectin/blood ; Adult ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*etiology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leptin/blood ; Logistic Models ; Middle Aged ; Premenopause/*blood ; Resistin/*blood ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Adipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk.

METHODS: The study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal-Wallis and Mann-Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis.

RESULTS: Resistin levels varied between histological types of breast cancer (p = 0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p < 0.014 and p < 0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154-0.862, p < 0.022).

CONCLUSION: Our findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.}, } @article {pmid27517320, year = {2016}, author = {Fu, Z and Chen, S and Liu, S and Han, S and Gao, X and Li, D and Li, D}, title = {DcR3 gene polymorphisms are associated with sporadic breast infiltrating ductal carcinoma in Northeast Chinese women.}, journal = {Oncotarget}, volume = {7}, number = {36}, pages = {57970-57977}, pmid = {27517320}, issn = {1949-2553}, mesh = {Adult ; Alleles ; Asian People/genetics ; Breast Neoplasms/ethnology/*genetics/pathology ; Carcinoma, Ductal, Breast/ethnology/*genetics/pathology ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Lymphatic Metastasis ; Middle Aged ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Tumor Necrosis Factor, Member 6b/*genetics ; }, abstract = {Decoy Receptor 3 (DcR3), also called TNFRSF6β, is a member of the tumor necrosis factor receptor superfamily and is a soluble receptor for FasL. DcR3 is overexpressed in cancers and contributes to tumorigenesis through immune suppression and promotion of angiogenesis. We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls. We also conducted a case-control study analyzing associations of DcR3 polymorphisms with breast IDC risk. Subjects included 531 females with breast IDC and 592 age-matched healthy controls. Four DcR3 single nucleotide polymorphism loci with minor frequencies of more than 5% (rs3208008, rs41309931, rs2297441 and rs1291207) were genotyped using polymerase chain reaction restriction fragment length polymorphism and sequencing. Our results revealed significant differences in rs41309931genotypes and alleles (P < 0.01). Based on Haploview software analysis, the haplotype block Ars3208008 Grs41309931 Grs2297441 Ars1291207 exhibited the highest frequency, but, haplotype blocks Ars3208008 Trs41309931 Grs2297441 Ars1291207 and Crs3208008 Grs41309931 Grs2297441 Ars1291207 were associated with breast IDC risk. This study also detected associations between DcR3 gene polymorphisms and the clinicopathological features of breast IDC, including lymph node metastasis and C-erbB2, P53, estrogen receptor and progesterone receptor status. These data indicate that DcR3 gene polymorphisms are associated with sporadic breast IDC risk in Northeast Chinese females.}, } @article {pmid27513287, year = {2016}, author = {George-Levi, S and Vilchinsky, N and Tolmacz, R and Khaskiaa, A and Mosseri, M and Hod, H}, title = {"It takes two to take": Caregiving style, relational entitlement, and medication adherence.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {30}, number = {6}, pages = {743-751}, doi = {10.1037/fam0000203}, pmid = {27513287}, issn = {1939-1293}, mesh = {Adult ; Aged ; Caregivers/*psychology ; Female ; Heart Diseases/*psychology ; Humans ; Male ; Medication Adherence/*psychology ; Middle Aged ; *Personality ; Spouses/*psychology ; }, abstract = {Partners' support has been associated with both patients' increased and decreased inclination toward health-promoting behaviors. Our hypothesis for understanding this enigma is that it is the interplay between partners' manner of care provision and patients' ability to accept these care efforts that may best predict patients' adherence. Thus, the current study's main goal was to examine the contribution of the interaction between caregivers' support style (sensitive and compulsive) and cardiac patients' sense of relational entitlement (restricted, excessive, assertive, entitlement expectations) to patients' medication adherence. The Adult Caregiving Questionnaire, the Sense of Relational Entitlement Scale, and the Medication Adherence Report Scale were administered to 114 cardiac patients and their partners, during patients' hospitalizations and 6 months later. The lowest levels of medication adherence were detected among patients high on restricted entitlement who were married to partners high on compulsive caregiving style. These findings strengthen our claim that it is the interaction between recipients' personality and providers' support style which explain self-regulatory processes that arise during times of family medical crises. (PsycINFO Database Record}, } @article {pmid27510520, year = {2016}, author = {Naidoo, K and Beardsley, B and Carder, PJ and Deb, R and Fish, D and Girling, A and Hales, S and Howe, M and Wastall, LM and Lane, S and Lee, AH and Philippidou, M and Quinn, C and Stephenson, T and Pinder, SE}, title = {Accuracy of classification of invasive lobular carcinoma on needle core biopsy of the breast.}, journal = {Journal of clinical pathology}, volume = {69}, number = {12}, pages = {1122-1123}, doi = {10.1136/jclinpath-2016-203886}, pmid = {27510520}, issn = {1472-4146}, mesh = {Biopsy, Large-Core Needle ; Breast/pathology ; Breast Neoplasms/classification/diagnostic imaging/*pathology ; Carcinoma, Lobular/classification/diagnostic imaging/*pathology ; Diagnostic Errors ; Female ; Humans ; Ireland ; Magnetic Resonance Imaging ; Neoplasm Invasiveness ; Reproducibility of Results ; United Kingdom ; }, abstract = {Although the UK National Institute for Health and Care Excellence guidelines recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC), preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core biopsy of the breast has not been previously investigated. Eleven pathology laboratories from the UK and Ireland submitted data on 1112 cases interpreted as showing features of ILC, or mixed ILC and IDC/no special type (NST)/other tumour type, on needle core biopsy through retrieval of histology reports. Of the total 1112 cases, 844 were shown to be pure ILC on surgical excision, 154 were mixed ILC plus another type (invariably ductal/NST) and 113 were shown to be ductal/NST. Of those lesions categorised as pure ILC on core, 93% had an element of ILC correctly identified in the core biopsy sample and could be considered concordant. Of cores diagnosed as mixed ILC plus another type on core, complete agreement between core and excision was 46%, with 27% cases of pure ILC, whilst 26% non-concordant. These data indicate that there is not a large excess of expensive MRIs being performed as a result of miscategorisation histologically.}, } @article {pmid27510020, year = {2016}, author = {Baloch, AH and Khosa, AN and Bangulzai, N and Shuja, J and Naseeb, HK and Jan, M and Marghazani, IB and Kakar, M and Baloch, DM and Cheema, AM and Ahmad, J}, title = {Novel Nonsense Variants c.58C>T (p.Q20X) and c.256G>T (p.E85X) in the CHEK2 Gene Identified in Breast Cancer Patients from Balochistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {7}, pages = {3623-3626}, pmid = {27510020}, issn = {2476-762X}, mesh = {Adult ; Breast Neoplasms/*genetics ; Checkpoint Kinase 2/*genetics ; Exons/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Middle Aged ; Mutation/*genetics ; Pakistan ; }, abstract = {Breast cancer is very common and the leading cause of cancer deaths among women globally. Hereditary cases account for 510% of the total burden and CHEK2, which plays crucial role in response to DNA damage to promote cell cycle arrest and repair or induce apoptosis, is considered as a moderate penetrance breast cancer risk gene. Our objective in the current study was to analyze mutations in related to breast cancer. A total of 271 individuals including breast cancer patients and normal subjects were enrolled and all 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.}, } @article {pmid27509976, year = {2016}, author = {Shaikh, F and Jamal, Q and Baig, S and Hadi, NI and Majeed, N}, title = {Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic Parameters in Primary Breast Tumors.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {7}, pages = {3363-3367}, pmid = {27509976}, issn = {2476-762X}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Pakistan ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants.

MATERIALS AND METHODS: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied.

RESULTS: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status.

CONCLUSIONS: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER2 positive tumors.}, } @article {pmid27509210, year = {2016}, author = {Granek, L and Krzyzanowska, MK and Nakash, O and Cohen, M and Ariad, S and Barbera, L and Levy, R and Ben-David, M}, title = {Gender differences in the effect of grief reactions and burnout on emotional distress among clinical oncologists.}, journal = {Cancer}, volume = {122}, number = {23}, pages = {3705-3714}, doi = {10.1002/cncr.30236}, pmid = {27509210}, issn = {1097-0142}, mesh = {Adult ; Anxiety Disorders/psychology ; Burnout, Professional/*psychology ; Canada ; Depression/*psychology ; Female ; Grief ; Humans ; Israel ; Job Satisfaction ; Male ; Medical Oncology ; Middle Aged ; Oncologists/*psychology ; Physicians/*psychology ; Quality of Life/psychology ; Sex Characteristics ; Stress, Psychological/*psychology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: The current study was conducted to examine gender differences in the effect of grief reactions and burnout on emotional distress among clinical oncologists.

METHODS: The participants included a convenience sample of 178 oncologists from Israel (52 of whom were women) and Canada (48 of whom were women). Oncologists completed a questionnaire package that included a sociodemographic survey, the General Health Questionnaire, a burnout measure, and the Adult Oncologists Grief Questionnaire. To examine the effect of grief reactions and burnout on emotional distress while controlling for country and past depression within each gender, 2 hierarchical linear regression analyses were computed.

RESULTS: Female oncologists reported significantly more grief responses to patient death (mean, 47.72 [standard deviation (SD), 8.71] and mean, 44.53 [SD, 9.19], respectively), more emotional distress (mean, 12.41 [SD, 4.36] and mean, 10.64 [SD, 3.99], respectively), and more burnout (mean, 2.59 [SD, 1.69] and mean, 1.84 [SD, 1.5], respectively). For both genders, higher levels of grief reactions were associated with greater emotional distress among those who reported high levels of burnout (P<.001). However, for men, the association between grief reactions and emotional distress also was documented at moderate levels of burnout (P<.001).

CONCLUSIONS: Patient death is a regular part of clinical oncology. It is essential that oncologists be able to cope effectively with this aspect of their work. The findings of the current study highlight the need to take into account the cumulative stressors that oncologists contend with when designing supportive interventions. Gender differences in burnout, reactions to patient death, and emotional distress need to be addressed to ensure the best quality of life for oncologists and the best quality of care for their patients. Cancer 2016;122:3705-14. © 2016 American Cancer Society.}, } @article {pmid27506606, year = {2016}, author = {Tanaka, K and Tokunaga, E and Inoue, Y and Yamashita, N and Saeki, H and Okano, S and Kitao, H and Oki, E and Oda, Y and Maehara, Y}, title = {Impact of Expression of Vimentin and Axl in Breast Cancer.}, journal = {Clinical breast cancer}, volume = {16}, number = {6}, pages = {520-526.e2}, doi = {10.1016/j.clbc.2016.06.015}, pmid = {27506606}, issn = {1938-0666}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Japan/epidemiology ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*metabolism ; Receptor Protein-Tyrosine Kinases/*metabolism ; Triple Negative Breast Neoplasms/*metabolism/mortality/pathology ; Vimentin/*metabolism ; Axl Receptor Tyrosine Kinase ; }, abstract = {BACKGROUND: The association between Axl and vimentin protein expression has been observed in several cell lines. However, the clinical importance of Axl and vimentin expression in breast cancer have not been fully determined.

PATIENTS AND METHODS: The expressions of Axl and vimentin were evaluated by immunohistochemistry in a total of 343 patients with invasive ductal carcinoma. The relationships between expression of Axl and vimentin and clinicopathologic characteristics and prognosis were analyzed.

RESULTS: Axl expression was classified into high (n = 170) and low (n = 173) expression groups. Axl expression alone was not associated with any clinicopathologic factor or prognosis. Coexistence of vimentin-positive and Axl-high expression was observed in 10.5% (n = 36). Vimentin-positive and Axl-high tumors were associated with triple-negative breast cancers (P = .0396) and with poor prognosis in terms of both recurrence-free survival (P = .0126) and overall survival (P = .0005) compared to the other groups, including vimentin-positive and Axl-low tumors, vimentin-negative and Axl-high tumors, and vimentin-negative and Axl-low tumors. Multivariate analysis showed that coexistence of vimentin-positive and Axl-high expression was an independent poor prognostic factor for recurrence-free survival (hazard ratio, 2.78; 95% confidence interval, 1.23-5.68; P = .0158) and overall survival (hazard ratio, 3.72; 95% confidence interval, 1.51-8.47; P = .0059).

CONCLUSION: Coexistence of vimentin-positive and Axl-high expression is a poor prognostic factor for primary breast cancer. Vimentin and Axl expression might contribute to the aggressive phenotype in breast cancer.}, } @article {pmid27503013, year = {2016}, author = {Li, SN and Zhang, XL and Cai, GL and Lin, RW and Jiang, H and Chen, JZ and Xu, B and Huang, W}, title = {Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.}, journal = {Chinese medical journal}, volume = {129}, number = {16}, pages = {1904-1911}, pmid = {27503013}, issn = {2542-5641}, mesh = {Aged ; Cardiomyopathy, Dilated/pathology/*physiopathology ; Electrocardiography ; Female ; Heart Failure/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC.

METHODS: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality.

RESULTS: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class.

CONCLUSIONS: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.}, } @article {pmid27501955, year = {2016}, author = {Serrero, G and Hawkins, DM and Bejarano, PA and Ioffe, O and Tkaczuk, KR and Elliott, RE and Head, JF and Phillips, J and Godwin, AK and Weaver, J and Hicks, D and Yue, B}, title = {Determination of GP88 (progranulin) expression in breast tumor biopsies improves the risk predictive value of the Nottingham Prognostic Index.}, journal = {Diagnostic pathology}, volume = {11}, number = {1}, pages = {71}, pmid = {27501955}, issn = {1746-1596}, support = {R43 CA124179/CA/NCI NIH HHS/United States ; U01 CA113916/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnosis/metabolism/mortality ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/*metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Progranulins ; Proportional Hazards Models ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: The Nottingham Prognostic Index (NPI), which combines numerical values for nodal status, tumor size and histological grade, is used in the standard of care to provide predictive value information on post-surgery survival for patients with primary breast cancer. Attempts to improve the performance of the NPI algorithm have been carried out by testing the inclusion of other biomarker expression and morphological features such as vascular invasion. In the present study, we investigated whether expression of the autocrine growth and survival factor GP88 (progranulin), known to be overexpressed in breast cancer, would improve NPI's predictive value.

METHODS: We examined by immunohistochemistry (IHC) the GP88 expression in 508 cases of estrogen receptor positive invasive ductal carcinoma with known clinical outcomes and for which NPI had been determined. GP88 IHC expression was scored by two board certified pathologists and classified into two score groups of GP88 <3+ (0, 1+, 2+) and GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) or overall survival (OS) outcomes was then examined by Kaplan-Meier analysis, Cox proportional Hazard (CPH) ratio and Pearson's X (2) test.

RESULTS: Kaplan-Meier survival graphs of cases categorized by their NPI scores (<3.4, 3.4-5.4, >5.4) and GP88 expression showed that for patients within the same NPI subgroup, patients having tumors with a high GP88 expression (GP88 IHC score of 3+) had a worse DFS than patients with tumors that had a low GP88 expression (GP88 IHC score <3+). When adjusted for NPI, high GP88 score was significantly associated with recurrence with a hazard ratio of 3.30 (95 % CI 2.12 to 5.14).

CONCLUSIONS: The data suggest that the determination of GP88 tumor expression at time of diagnosis for early stage breast cancer patients can provide additional survival information to that provided by NPI alone and thus may be useful for risk management of patients diagnosed with breast cancer.}, } @article {pmid27501708, year = {2017}, author = {Chang, RY and Cheung, PS}, title = {Nipple Preservation in Breast Cancer Associated with Nipple Discharge.}, journal = {World journal of surgery}, volume = {41}, number = {1}, pages = {176-183}, pmid = {27501708}, issn = {1432-2323}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Mammography ; Margins of Excision ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local ; *Nipple Discharge ; *Nipples ; *Organ Sparing Treatments ; Radiotherapy, Adjuvant ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast carcinoma presented with nipple discharge is a rare condition. There is theoretical concern about preserving nipple in these patients since the risk of nipple-areolar complex involvement may be greater, but not many studies in the literature have addressed on this issue. The aim of the current study was to determine the incidence and outcome of nipple preservation in breast cancer associated with nipple discharge.

METHODS: Medical records of patients who were diagnosed to have breast carcinoma and presented with nipple discharge from May 2009 to October 2014 were retrospectively reviewed.

RESULTS: Sixty patients presented with nipple discharge were diagnosed with breast cancer, which represent 3.8 % of all patients who underwent breast cancer surgery in our unit during the study period. Forty-six patients (76.7 %) had nipple discharge as their only symptom, while the rest also presented with breast mass clinically or radiologically. All patients had mammogram and ultrasound performed, and 53.3 and 63.3 % respectively showed suspicious findings. Forty-one out of 46 (89.1 %) nipple discharge cytology were inadequate or benign. Thirty-two microdochectomy were performed. Routine frozen section was utilized intra-operatively to ensure clear margins. The most common histology was ductal carcinoma in situ (DCIS) (n = 29, 48.3 %), followed by DCIS with invasive ductal carcinoma (n = 23, 38.3 %). Regarding treatment, 26 patients (43.3 %) had nipple preserved, including 21 breast conservative surgery and five nipple-sparing mastectomies. Overall, no local or systemic recurrence was observed at a median follow-up of 27 months. Ten out of 34 (29.4 %) mastectomy specimens showed NAC involvement on pathology. By comparing patients with NAC preserved to patients with NAC removed, no significant preoperative predictors were identified.

CONCLUSION: Breast carcinoma patients who present with nipple discharge usually have early-stage cancer. Presence of nipple discharge is not equivalent to NAC involvement. Nipple preservation can be oncologically safe if negative margins are ascertained.}, } @article {pmid27499770, year = {2016}, author = {Dabiri, S and Moeini Aghtaei, M and Shahryari, J and Shamis Meymandi, M and Amirpour-Rostami, S and Foutohi Ardekani, R}, title = {Maspin Gene Expression in Invasive Ductal Carcinoma of Breast.}, journal = {Iranian journal of pathology}, volume = {11}, number = {2}, pages = {104-111}, pmid = {27499770}, issn = {1735-5303}, abstract = {BACKGROUND: The breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine protease inhibitor (Maspin) gene expression possibly secreted by myoepithelial cells, grade of breast cancer and other prognostics factors (ER, PR, and c-erb-B2).

METHODS: Paraffin embedded blocks of 31 breast cancer patients together with two normal breast tissues were used for IHC staining and Maspin gene RNA detection uses the real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and Extract the cDNA of different samples for evaluating the Maspin RNA level.

RESULTS: We found that the RNA level was considerably lowerin these cancer samples compared with normal samples. In addition, different grades of breast cancer in the obtained results adopt some distinguishable values. The Maspin expression in samples with grades II and III is much lower than the ones in normal group (P<0.05) which could be considered as a promising way in diagnosing of this disease. The results showed no considerable differences in Maspin gene expression of the c-erb-B2 scores in the tumor group except the samples having score 0. The other observation of this research study confirmed that Maspin gene expression couldn't show any differences between the values of both ER and PR in different scores of the tumor group. On the other hand, the cDNA of these patients showed lower values compared with normal samples.

CONCLUSION: Maspin expression was reduced in samples with grade II& III of invasive ductal carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more expression happened in normal group comparing with different scores of it. We could suggest that there was a reverse relationship between tumor formation and Maspin gene expression. These results showed possible role of Maspin as prognostic factor.}, } @article {pmid27493488, year = {2016}, author = {Sannomiya, N and Hattori, Y and Ueda, N and Kamida, A and Koyanagi, Y and Nagira, H and Ikunishi, S and Shimabayashi, K and Hashimoto, Y and Murata, A and Sato, K and Hirooka, Y and Hosoya, K and Ishiguro, K and Murata, Y and Hirooka, Y}, title = {Correlation between Ultrasound Findings of Tumor Margin and Clinicopathological Findings in Patients with Invasive Ductal Carcinoma of the Breast.}, journal = {Yonago acta medica}, volume = {59}, number = {2}, pages = {163-168}, pmid = {27493488}, issn = {0513-5710}, abstract = {BACKGROUND: Breast ultrasound findings regarding tumor margins are crucial in judging whether a tumor is malignant or benign. However, the relationships between the margins and clinicopathological characteristics remain largely unknown. In this study, we examined the clinicopathological characteristics of patients with invasive ductal carcinoma whose ultrasound images showed either well-defined and rough or indistinct margins.

METHODS: Of all consecutive patients diagnosed with invasive ductal carcinoma at the Division of Breast and Endocrine Surgery of Tottori University Hospital from January 2012 to December 2014, 122 patients whose ultrasound images showed either "well-defined and rough" or "indistinct" tumor margins were included in this study. Mammography and ultrasound images taken at the initial examination were reviewed. Patients were divided into two groups based on ultrasound findings of the tumor margins: the "well-defined and rough group" and the "indistinct group." The relationships among ultrasound findings, mammography findings and clinicopathological findings were investigated in the two groups.

RESULTS: The well-defined and rough group was more likely to contain solid-tubular carcinoma, while the indistinct group was more likely to contain scirrhous carcinoma. The MIB-1 index was higher in the well-defined and rough group than in the indistinct group. Additionally, the proportion of patients with nuclear grade 3, estrogen receptor-negative/progesterone receptor-negative, and triple-negative breast cancer was greater in the well-defined and rough group than in the indistinct group.

CONCLUSION: Invasive ductal carcinomas with well-defined and rough margins on ultrasound were likely to be malignant and proliferative than those with indistinct margins.}, } @article {pmid27492008, year = {2016}, author = {Li, G and Yang, S and Yao, J and Wang, Z and Yao, G and Liu, M and Ye, C}, title = {Invasive micropapillary carcinoma of the breast had poor clinical characteristics but showed no difference in prognosis compared with invasive ductal carcinoma.}, journal = {World journal of surgical oncology}, volume = {14}, number = {1}, pages = {207}, pmid = {27492008}, issn = {1477-7819}, mesh = {Breast Neoplasms/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Carcinoma, Papillary/*mortality/pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: It is controversial for prognosis of invasive micropapillary carcinoma (IMPC) compared with invasive ductal carcinoma (IDC) of the breast. To better understand the difference between IMPC and IDC prognoses, we conducted this retrospective study.

METHODS: Data from 33 patients with IMPC were retrospectively reviewed, and the clinicopathologic characteristics and survival status were compared with those of 347 patients with IDC who were treated during the same period.

RESULTS: The IMPC cases were of larger tumor size, greater proportion of nodal involvement, and an increased incidence of lymphovascular invasion compared with IDC cases. The overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) rates were not significantly different between IMPC and IDC. The 3-year OS rate was 97 vs 94.2 % for the IMPC and IDC patients, respectively. The 3-year FFS rate was 87.9 vs 86.2 % for the IMPC and IDC patients, respectively. For IMPC patients, the 3-year LRFS rate was 93.9 % and in IDC patients was 89.0 %. The 3-year DMFS rates of IMPC patients was 90.9 % and IDC patients was 89 %.

CONCLUSIONS: IMPC had poor clinical characteristics, but it showed no difference in OS, FFS, LRFS, and DMFS compare with IDC.}, } @article {pmid27483711, year = {2016}, author = {Ursaru, M and Jari, I and Gheorghe, L and Naum, AG and Scripcariu, V and Negru, D}, title = {BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {120}, number = {2}, pages = {316-320}, pmid = {27483711}, issn = {0048-7848}, mesh = {Adult ; Breast Neoplasms/*diagnosis/mortality/surgery ; Carcinoma, Ductal, Breast/*diagnosis/mortality/surgery ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*diagnosis/mortality/surgery ; Neoplasm Staging ; Neoplasms, Multiple Primary/*diagnosis/mortality/surgery ; Neoplasms, Second Primary/*diagnosis/mortality/surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIM: To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer.

MATERIAL AND METHODS: 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis.

RESULTS: Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death.

CONCLUSIONS: Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.}, } @article {pmid27482285, year = {2016}, author = {Barroso-Sousa, R and Metzger-Filho, O}, title = {Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications.}, journal = {Therapeutic advances in medical oncology}, volume = {8}, number = {4}, pages = {261-266}, pmid = {27482285}, issn = {1758-8340}, abstract = {Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications.}, } @article {pmid27479041, year = {2016}, author = {Sabiani, L and Houvenaeghel, G and Heinemann, M and Reyal, F and Classe, JM and Cohen, M and Garbay, JR and Giard, S and Charitansky, H and Chopin, N and Rouzier, R and Daraï, E and Coutant, C and Azuar, P and Gimbergues, P and Villet, R and Tunon de Lara, C and Lambaudie, E}, title = {Breast cancer in young women: Pathologic features and molecular phenotype.}, journal = {Breast (Edinburgh, Scotland)}, volume = {29}, number = {}, pages = {109-116}, doi = {10.1016/j.breast.2016.07.007}, pmid = {27479041}, issn = {1532-3080}, mesh = {Adult ; *Age Factors ; Breast Neoplasms/chemistry/drug therapy/*pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; France ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/etiology ; *Phenotype ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {PURPOSE: Controversy exists about the prognosis of breast cancer in young women. Our objective was to describe clinicopathological and prognostic features to improve adjuvant treatment indications.

METHODS: We conducted a retrospective multi centre study including fifteen French hospitals. Disease-free survival's data, clinical and pathological criteria were collected.

RESULTS: 5815 patients were included, 15.6% of them where between 35 and 40 years old and 8.7% below 35. In 94% of the cases, a palpable masse was found in patients ≤35 years old. Triple negative and HER2 tumors were predominantly found in patients ≤35 (22.2% and 22.1%, p < 0.01). A young age ≤40 years (p < 0.001; hazard ratio [HR]: 2.05; 95% confidence limit [CL]: 1.60-2.63) or ≤35 years (p < 0.001; [HR]: 3.86; 95% [CL]: 2.69-5.53) impacted on the indication of chemotherapy. Age ≤35 (p < 0.001; [HR]: 2.01; 95% [CL]: 1.36-2.95) was a significantly negative factor on disease-free survival. Chemotherapy (p < 0.006; [HR]: 0.6; 95% [CL]: 0.40-0.86) and positive hormone receptor status (p < 0.001; [HR]: 0.6; 95% [CL]: 0.54-0.79) appeared to be protector factors. Patients under 36, had a significantly higher rate of local recurrence and distant metastasis compared to patients >35-40 (21.5 vs. 15.4% and 21.8 vs. 12.6%, p < 0.01).

CONCLUSION: Young women present a different distribution of molecular phenotypes with more luminal B and triple negative tumors with a higher grade and more lymph node involvement. A young age, must be taken as a pejorative prognostic factor and must play a part in indication of adjuvant therapy.}, } @article {pmid27478003, year = {2016}, author = {Peters, AS and Lercher, M and Fleming, TH and Nawroth, PP and Bischoff, MS and Dihlmann, S and Böckler, D and Hakimi, M}, title = {Reduced glyoxalase 1 activity in carotid artery plaques of nondiabetic patients with increased hemoglobin A1c level.}, journal = {Journal of vascular surgery}, volume = {64}, number = {4}, pages = {990-994}, doi = {10.1016/j.jvs.2016.04.025}, pmid = {27478003}, issn = {1097-6809}, mesh = {Aged ; Biomarkers/blood ; Carotid Arteries/*enzymology/pathology/surgery ; Carotid Artery Diseases/blood/diagnosis/*enzymology/surgery ; Case-Control Studies ; Down-Regulation ; Endarterectomy, Carotid ; Erythrocytes/enzymology ; Female ; Glycated Hemoglobin/*analysis ; Humans ; Lactoylglutathione Lyase/*analysis ; Male ; Middle Aged ; *Plaque, Atherosclerotic ; Up-Regulation ; }, abstract = {OBJECTIVE: Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level.

METHODS: HbA1c level was determined in venous blood of patients with carotid artery disease. Protein level of GLO1 was measured in endarterectomy-derived carotid artery plaques by Western blotting. Activity was measured by spectrophotometric assay in the plaques as well as in the erythrocytes; GLO1 activity in erythrocytes was compared with that in a cohort of healthy individuals (n = 15; 33% men; average age, 60 years).

RESULTS: There were 36 patients with carotid artery disease (69% men; average age, 69 years) included in this study and divided into two equal groups: group I, HbA1c < 5.7% (<39 mmol/mol); and group II, 5.7% ≤ HbA1c < 6.5% (39 mmol/mol ≤ HbA1c < 48 mmol/mol). GLO1 activity in carotid plaques was reduced by 29% in group II compared with group I (P = .048), whereas protein expression was unchanged (P = .25). Analysis of GLO1 activity in erythrocytes revealed no difference between the groups (P = .36) or in comparison to healthy controls (P = .15). Examination of clinical parameters showed an increased amount of patients with concomitant peripheral arterial disease in group II (44% vs 10%; P = .020).

CONCLUSIONS: Reduction of GLO1 activity in atherosclerotic lesions of nondiabetic patients with increased HbA1c is associated with a functional involvement of this protective enzyme in atherogenesis. Systemic GLO1 activity seems to be independent of both HbA1c and localized atherosclerosis as it was unchanged between group I and group II as well as compared with healthy controls, respectively.}, } @article {pmid27477923, year = {2016}, author = {Streckfus, CF and Bigler, L}, title = {A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {30800}, pmid = {27477923}, issn = {2045-2322}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Mass Spectrometry ; Neoplasm Proteins/*metabolism ; Precision Medicine/methods ; Salivary Proteins and Peptides/*metabolism ; }, abstract = {The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care.}, } @article {pmid27474504, year = {2017}, author = {Quéro, L and Guillerm, S and Taright, N and Michaud, S and Teixeira, L and Cahen-Doidy, L and Bourstyn, E and Espié, M and Hennequin, C}, title = {10-Year follow-up of 621 patients treated using high-dose rate brachytherapy as ambulatory boost technique in conservative breast cancer treatment.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {122}, number = {1}, pages = {11-16}, doi = {10.1016/j.radonc.2016.06.014}, pmid = {27474504}, issn = {1879-0887}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brachytherapy/*methods ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/mortality ; Radiation Dosage ; }, abstract = {PURPOSE: Breast conserving treatment, consisting of lumpectomy followed by whole-breast irradiation, is considered the standard of care in early-stage breast cancer. Randomized studies have reported that delivering boost doses to tumor bed improves local control rates, particularly in young women. This study sought to evaluate local control and cosmetic results of delivering boost doses using a high-dose-rate (HDR) brachytherapy (HDRBT) in breast cancer conservative treatment.

METHODS: We included 621 T1-T2, N0-N1 breast cancer patients who underwent lumpectomy, external irradiation (44Gy over 5weeks), and a boost dose of two fractions of 5Gy to the tumor bed by means of HDR iridium brachytherapy. Implantation was performed during the lumpectomy or 2-3weeks after external irradiation. Population characteristics were as follows: pTis=11.6%; pT1=63.4%; pT2=25.0%; median tumor size=1.5cm; histology: ductal carcinoma in situ (DCIS): 72 (11.6%); infiltrative ductal carcinoma (IDC): 471 (75.8%); other: 78 (12.6%). For IDCs, the surgical margins were positive in 38cases (6.2%) and an extensive intraductal component was present in 254 cases.

RESULTS: With a median follow-up of 10.3years, 47 local relapses were observed (10-year local relapse rate: 7.4%). Small-volume implantation (V100<45cc) and ductal carcinoma in situ histology both significantly correlated with local relapse. The 10-year overall survival was 91%. Cosmetic results were evaluated in 264patients, proving excellent in 58 (22%), good in 153 (58%), fair in 40 (15%), and poor in 13 (5%).

CONCLUSIONS: Small implant volume and ductal carcinoma in situ histology significantly correlated with local relapse following HDR brachytherapy dose boost in breast cancer conservative treatment. Modern image-guided breast brachytherapy techniques using surgical clips as a guide may decrease potential treatment targeting errors, consequently improving local control without increasing toxicity.}, } @article {pmid27469595, year = {2016}, author = {Park, CK and Jung, WH and Koo, JS}, title = {Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.}, journal = {Breast cancer research and treatment}, volume = {159}, number = {1}, pages = {55-69}, doi = {10.1007/s10549-016-3929-2}, pmid = {27469595}, issn = {1573-7217}, mesh = {Antigens/metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Cancer-Associated Fibroblasts/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Endopeptidases ; Female ; Gelatinases/metabolism ; Humans ; Membrane Glycoproteins/metabolism ; Membrane Proteins/metabolism ; Prolyl Hydroxylases/metabolism ; Proteoglycans/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; S100 Calcium-Binding Protein A4/metabolism ; Serine Endopeptidases/metabolism ; Tissue Array Analysis ; }, abstract = {Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.}, } @article {pmid27461644, year = {2016}, author = {Ding, JR and Wang, DN and Pan, JL}, title = {Apparent diffusion coefficient value of diffusion-weighted imaging for differential diagnosis of ductal carcinoma in situ and infiltrating ductal carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {12}, number = {2}, pages = {744-750}, doi = {10.4103/0973-1482.154093}, pmid = {27461644}, issn = {1998-4138}, mesh = {Breast Carcinoma In Situ/*diagnosis ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Odds Ratio ; Publication Bias ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The present meta-analysis investigated the clinical value of apparent diffusion coefficient (ADC) values in diffusion-weighted imaging (DWI) for differential diagnosis of ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC).

MATERIALS AND METHODS: Electronic databases searches were employed to identify relevant scientific literature, and the search results were screened to selected high-quality studies for this meta-analysis. Methodological quality of the enrolled studies was evaluated by quality evaluation of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and its corresponding 95% confidence interval (95% CI) were calculated for DCIS versus IDC category of ADC value using Z test.

RESULTS: Our meta-analysis contained a combined total of 1,097 subjects (928 patients with IDC and 169 patients with DCIS) from 9 relevant high-quality cohort studies. Pooled ORs demonstrated that ADC value in IDC patients was significantly lower than DCIS patients. Subgroup analysis stratified by ethnicity indicated a higher ADC value in DCIS patients compared to IDC, in Asian population, but not in Caucasians. Magnetic resonance imaging (MRI) machine type-stratified analysis revealed that the ADC value of DWI obtained from both non- General Electric Company (GE) 1.5T and GE 1.5T machines were highly reliable in the differential diagnosis of DCIS and IDC.

CONCLUSION: Our meta-analysis provides evidence that ADC values in DWI accurately conveys the differences in tumor architecture between IDC and DCIS, which has high clinical value in differentiatal diagnosis of IDC and DCIS. This may lead to improved BC prediction and treatment.}, } @article {pmid27460667, year = {2016}, author = {Fu, L and Luo, S and Cai, S and Hong, W and Guo, Y and Wu, J and Liu, T and Zhao, C and Li, F and Huang, H and Huang, M and Wang, J}, title = {Identification of LAMP2 Mutations in Early-Onset Danon Disease With Hypertrophic Cardiomyopathy by Targeted Next-Generation Sequencing.}, journal = {The American journal of cardiology}, volume = {118}, number = {6}, pages = {888-894}, doi = {10.1016/j.amjcard.2016.06.037}, pmid = {27460667}, issn = {1879-1913}, mesh = {Adolescent ; Age of Onset ; Blotting, Western ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Hypertrophic/*genetics/metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Codon, Nonsense ; Female ; Fluorescent Antibody Technique ; Genotype ; Glycogen Storage Disease Type IIb/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Lysosomal-Associated Membrane Protein 2/*genetics/metabolism ; Male ; Muscle, Skeletal/metabolism ; *Mutation ; Myocardium/metabolism ; Phenotype ; Sequence Analysis, DNA ; Wolff-Parkinson-White Syndrome/genetics ; }, abstract = {Danon disease is an X-linked disorder with the clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Early diagnosis of this disease remains a challenge, especially in the pediatric population. In this study, we developed a targeted panel-based next generation sequencing pipeline to identify mutations by sequencing of selected candidate genes in 136 pediatric patients with either hypertrophic cardiomyopathy (HC) or idiopathic dilated cardiomyopathy (IDC). This led to the identification of lysosome-associated membrane protein 2 (LAMP2) mutations in 4 of the 64 (6%) probands with HC, including 3 novel nonsense mutations (p.Q240X, p.S250X, and p.G22X). No LAMP2 mutation was detected in the other 72 probands with IDC. All 4 probands and one additional affected family member (2 men and 3 women) had an early-onset age and presented either HC alone or combined with Wolff-Parkinson-White syndrome and skeletal myopathy. Immunofluorescence staining and Western blot analysis revealed absent LAMP2 expression in both cardiac and skeletal muscle samples of the first proband and severely decreased LAMP2 expression in the skeletal muscle samples of the second proband. In conclusion, cardiomyopathy in the patients with Danon disease may occur during early childhood and tend to be HC rather than IDC in both affected men and women. Therefore, Danon disease should be considered as one of the leading causes of unexplained ventricular hypertrophy in pediatric patients. The inclusion of LAMP2 gene in cardiomyopathy genetic screening panels may contribute to early diagnosis of Danon disease.}, } @article {pmid27453807, year = {2016}, author = {Bouffard, J and Berger, E and Armstrong, GS}, title = {The effectiveness of specialized legal counsel and case management services for indigent offenders with mental illness.}, journal = {Health & justice}, volume = {4}, number = {}, pages = {7}, pmid = {27453807}, issn = {2194-7899}, abstract = {BACKGROUND: In recent years, jurisdictions have recognized the strain placed on limited existing resources by criminal offenders with mental illness who frequently cycle through local jail facilities. In response, many locales have developed and implemented specialized programs to more effectively and efficiently manage these offenders, particularly the process of assigning defense attorneys to these often indigent defendants.

METHODS: The current study examined the impact of an Indigent Defense Counsel (IDC) program designed to provide specially trained defense attorneys, and enhanced case management services to 257 indigent jail inmates with a qualifying, major mental health diagnosis (e.g., major depression). These offenders were compared to 117 similar offenders who did not receive these services, on both their length of stay in the jail, and their likelihood of recidivism after release to the community.

RESULTS: Survival analyses revealed that program participants spent about 17 fewer days in jail; however, recidivism rates between groups, measured as return to the same county jail or as statewide re-arrest, did not differ.

CONCLUSIONS: These results suggest that defendants with mental illness can potentially be managed effectively in the community, with little added risk to public safety and at potential savings in jail bed days/costs. Implications for the processing of indigent criminal defendants with mental illness are presented.}, } @article {pmid27453779, year = {2016}, author = {Sule, EA and Nzegwu, MA}, title = {Attaining pathological complete regression for breast conservation - A pilot experience in a developing country.}, journal = {Annals of medicine and surgery (2012)}, volume = {9}, number = {}, pages = {61-66}, pmid = {27453779}, issn = {2049-0801}, abstract = {CONTEXT: Local recurrence is a formidable risk consideration in employing breast conservation for breast cancer. However pathological complete regression (PCR) from chemotherapy has been associated with improved rates of recurrence. Lower PCR rates have been reported from earlier studies and our approach seeks to obtain higher PCR rates utilizing a two pronged approach of surgery and chemotherapy.

OBJECTIVE: To determine success rates in attaining pathologically complete regression for breast conservation in non-metastatic breast cancer cases in a developing country and their clinical outcome.

PATIENTS AND METHODS: Patients diagnosed with early stage breast cancers had sequential anthracycline/taxane based neoadjuvant/adjuvant chemotherapy administered at three weekly intervals. Following an initial excision, re-excisions were done following three courses of doxorubicin based chemotherapy. Subsequent re-excisions in cases with failed complete pathological regression were repeated following additional three doxorubicin based chemotherapy cycles or at sequel third taxane based cycle. Endpoint was pathologically complete regression as determined on permanent sections.

RESULTS: Patients ages ranged between 27 and 67 years, mean age 43years, SD 10.34 years, N = 20 Initial breast tumour sizes ranged between 0.5 and 9 cm, mean 4.05 cm, SD 2.38. There were three T4, four T3 tumours, seven T2 and six T1 tumours. Clinical axillary lymphadenopathy with pathological involvement was present in 11 cases. Histological diagnosis showed 13 cases of invasive ductal carcinoma (65.0%), 2 cases of ductal carcinoma insitu (10.0%), 1 papillary carcinoma (5.0%), 3 cases of invasive lobular carcinoma (15.0%) and non-specific type 1 (5.0%). Immunohistochemistry assessment available in 15 cases was positive for estrogen and progesterone receptors in 10 cases. Two cases (10.0%) exhibited 20% positivity for human epidermal growth factor receptor. Pathological complete regression (PCR) defined as no invasive or insitu tumour residuals in the excised tumour bed, was achieved in the 18 cases assessed. (100%) This was consistent with clinical complete response obtained. It was not determined in 2 cases though clinical complete response was obtained. PCR was determined in ten cases (50.0%) at the first reexcision, second reexcision in 4 cases (20.0%) and third reexcision in 4 cases (20.0%). Mean no of re-excisions 1.67 cm, SD 0.84. Six sequential anthracycline/taxane cycles were administered in 17 cases while three cases received anthracycline based chemotherapy only. Median duration of followup from diagnosis was 48 months ranging between 8 months and 144 months. There were two demises at 48 months and 36 months follow up.

CONCLUSION: Extended chemotherapy sessions alongside re-excisions were successful in achieving much enhanced rates of pathologically complete remissions at 100% in this yet early report, thus improving breast conservation rates even for T3 and T4 tumours. Our study reports higher PCR rates.}, } @article {pmid27453513, year = {2016}, author = {Merlo, M and Anzini, M and Bussani, R and Artico, J and Barbati, G and Stolfo, D and Gigli, M and Muça, M and Naso, P and Ramani, F and Di Lenarda, A and Pinamonti, B and Sinagra, G}, title = {Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {118}, number = {6}, pages = {895-900}, doi = {10.1016/j.amjcard.2016.05.063}, pmid = {27453513}, issn = {1879-1913}, mesh = {Adult ; Cardiomyopathy, Dilated/*etiology/mortality/surgery ; Cohort Studies ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mortality ; Multivariate Analysis ; Myocarditis/*complications ; Prognosis ; Proportional Hazards Models ; Protective Factors ; Risk Factors ; Ventricular Dysfunction, Left/*etiology/mortality/surgery ; }, abstract = {Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.}, } @article {pmid27449764, year = {2016}, author = {Hamza, AR and Bicaj, BX and Kurshumliu, FI and Zejnullahu, VA and Sada, FE and Krasniqi, AS}, title = {Mesenteric Meckel's diverticulum or intestinal duplication cyst: A case report with review of literature.}, journal = {International journal of surgery case reports}, volume = {26}, number = {}, pages = {50-52}, pmid = {27449764}, issn = {2210-2612}, abstract = {INTRODUCTION: A Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal (GI) tract. They arise from the middle-to-distal ileum. Contrary to MD, intestinal duplication cyst (IDC) is uncommon congenital anomaly of GI, but can occur anywhere from the tongue to the anus.

PRESENTATION OF CASE: Here we report an 18-year-old male who presented to the department of abdominal surgery with chronic abdominal pain, frequent vomiting and mild abdominal distension. Following radiological investigation, a laparotomy was performed with the preoperative diagnosis of a mesenteric cyst. Intraoperativelly it became apparent that the cystic mass was on the mesenteric aspect of the small bowel without intestinal communication. Resection of the cyst was performed. Histological examination of the specimen revealed the presence of gastric tissue, which resembles MD. Although, the exact diagnosis of this cystic mass is ambiguous between MD and IDC, because of similar clinical signs, their complications and presence of gastric mucosa, however surgical treatment is gold standard of both.

CONCLUSION: This case report underlines the necessity of how to differentiate between MD and IDC, although, surgical management is recommended for both.}, } @article {pmid27447822, year = {2016}, author = {Lee, CY and Hochman, G and Prince, SE and Ariely, D}, title = {Past Actions as Self-Signals: How Acting in a Self-Interested Way Influences Environmental Decision Making.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0158456}, pmid = {27447822}, issn = {1932-6203}, mesh = {Adult ; Attitude ; *Conservation of Natural Resources ; *Decision Making ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Motivation ; *Self Concept ; Social Behavior ; Surveys and Questionnaires ; }, abstract = {In the last few decades, awareness of environmental issues has increased significantly. Little has changed, however, in human activities contributing to environmental damage. Why is it so difficult for us to change our behavior in a domain that is clearly so important to the future of humanity? Here we propose and test the possibility that self-signaling, the way we view ourselves based on our past behaviors, is one of the factors contributing to the difficulty of taking environmental action. In three experiments, we show that previous self-interested thoughts or behaviors serve as important signals that hinder the likelihood of acting in line with an individual's reported concern for the environment. This study not only helps explain the gap between environmental awareness and action, but also suggests alternative strategies for policymakers and environmental agencies to promote proenvironmental behavior.}, } @article {pmid27447600, year = {2016}, author = {Xia, X and Kim, S and Liu, C and Shim, SH}, title = {Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities.}, journal = {Molecules (Basel, Switzerland)}, volume = {21}, number = {7}, pages = {}, pmid = {27447600}, issn = {1420-3049}, mesh = {Ascomycota/*chemistry/metabolism ; Biological Products/*chemistry/*pharmacology ; Endophytes ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Proteasome Endopeptidase Complex ; Proteasome Inhibitors/*chemistry/*pharmacology ; Secondary Metabolism ; }, abstract = {Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1-4) and seven α-pyrone analogues (5-10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1-3, 5, and 9-10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC50 of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors.}, } @article {pmid27446451, year = {2016}, author = {Jiang, L and Jing, C and Kong, X and Li, X and Ma, T and Huo, Q and Chen, J and Wang, X and Yang, Q}, title = {Comparison of adjuvant ED and EC-D regimens in operable breast invasive ductal carcinoma.}, journal = {Oncology letters}, volume = {12}, number = {2}, pages = {1448-1454}, pmid = {27446451}, issn = {1792-1074}, abstract = {In China, the adjuvant epirubicin and docetaxel (ED) regimen is widely used as a substitute for the epirubicin and cyclophosphamide followed by docetaxel (EC-D) regimen in patients with operable breast cancer. However, their equivalence has not yet been demonstrated. This retrospective study compared these two adjuvant regimens as regards feasibility, safety and efficacy. Data on consecutive patients who received either ED (70/75 mg/m[2] every 3 weeks for 6 cycles) or EC-D (70/600 mg/m[2] epirubicin/cyclophosphamide followed by 75 mg/m[2] docetaxel every 3 weeks for 4 cycles each) as their adjuvant chemotherapy in our center from January 2009 to January 2014, were analyzed. A total of 374 patients was enrolled, among whom 250 patients received the ED regimen, and 124 patients received the EC-D regimen. The overall median follow-up time was 38.6 months. In total, 90 and 94.4% of patients in the ED and EC-D groups, respectively, completed full cycles of chemotherapy (P=0.174). There was no difference in efficacy in terms of disease-free survival (DFS) and overall survival (OS) (DFS, P=0.919; OS, P=0.069). The incidence of neutropenia in the ED group was similar to that in the EC-D group (81.2 vs. 78.9%, P=0.660) with a similar utilization rate of granulocyte-colony stimulating factor (G-CSF; 76.9 vs. 75.2%, P=0.850). However, grade 3/4 gastrointestinal reactions were more frequently observed in the patients who received the EC-D regimen (42.0 vs. 29.2%, P=0.058). The findings of our study indicate that with similar feasibility, safety and mid-term efficacy, the adjuvant ED regimen for 6 cycles may be an alternative to the EC-D regimen in operable breast cancer.}, } @article {pmid27435300, year = {2017}, author = {Monica, MA and Baccarini, P and Cucchi, MC and Lacava, N and Foschini, MP}, title = {Endobronchial Pagetoid Spread of a Breast Carcinoma Metastatic to the Lung.}, journal = {International journal of surgical pathology}, volume = {25}, number = {1}, pages = {83-86}, doi = {10.1177/1066896916660619}, pmid = {27435300}, issn = {1940-2465}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Bronchi/pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/*secondary ; Neoplasm Invasiveness/*pathology ; }, abstract = {A case of endobronchial pagetoid spread of a breast carcinoma metastatic to the lung is described. A 73-year-old woman underwent wedge lung resection after the cytological diagnosis of lung metastasis from ductal invasive breast carcinoma. The breast carcinoma had been surgically removed 6 years previously; at the time of diagnosis it was a T1N0, grade 3 invasive ductal carcinoma, with HER-2 amplification. The lung metastasis measured 1,9 cm and showed the same histology and biological profile of the primary tumor. In addition, numerous neoplastic cells, with large cytoplasm and atypical nuclei, appear to spread along the mucosa of the bronchi adjacent to the metastatic lesion as well as that of the main lobar bronchus, intermingled with the columnar ciliated cells. The neoplastic elements were negative for TTF-1 and strongly HER-2 positive; these features appeared consistent with endobronchial pagetoid spread by the metastatic breast carcinomatous cells.}, } @article {pmid27432555, year = {2017}, author = {Ben-David, BM and Icht, M}, title = {Oral-diadochokinetic rates for Hebrew-speaking healthy ageing population: non-word versus real-word repetition.}, journal = {International journal of language & communication disorders}, volume = {52}, number = {3}, pages = {301-310}, doi = {10.1111/1460-6984.12272}, pmid = {27432555}, issn = {1460-6984}, mesh = {Aged ; Aged, 80 and over ; *Aging ; Apraxias/*diagnosis/*therapy ; Articulation Disorders/*diagnosis/*therapy ; Female ; Humans ; Israel ; *Jews ; *Language ; Male ; Reference Values ; Sex Factors ; Speech Articulation Tests ; Speech Production Measurement ; }, abstract = {BACKGROUND: Oral-diadochokinesis (oral-DDK) tasks are extensively used in the evaluation of motor speech abilities. Currently, validated normative data for older adults (aged 65 years and older) are missing in Hebrew. The effect of task stimuli (non-word versus real-word repetition) is also non-clear in the population of older adult Hebrew speakers.

AIMS: (1) To establish a norm for oral-DDK rate for older adult (aged 65 years and older) Hebrew speakers, and to investigate the possible effect of age and gender on performance rate; and (2) to examine the effects of stimuli (non-word versus real word) on oral-DDK rates.

METHODS & PROCEDURES: In experiment 1, 88 healthy older Hebrew speakers (60-95 years, 48 females and 40 males) were audio-recorded while performing an oral-DDK task (repetition of /pataka/), and repetition rates (syllables/s) were coded. In experiment 2, the effect of real-word repetition was evaluated. Sixty-eight older Hebrew speakers (aged 66-95 years, 43 females and 25 males) were asked to repeat 'pataka' (non-word) and 'bodeket' (Hebrew real word).

OUTCOMES & RESULTS: Experiment 1: Oral-DDK performance for older adult Hebrew speakers was 5.07 syllables/s (SD = 1.16 syllables/s), across age groups and gender. Comparison of this data with Hebrew norms for younger adults (and equivalent data in English) shows the following gradient of oral-DDK rates: ages 15-45 > 65-74 > 75-86 years. Gender was not a significant factor in our data. Experiment 2: Repetition of real words was faster than that of non-words, by 13.5%.

The paper provides normative values for oral-DDK rates for older Hebrew speakers. The data show the large impact of ageing on oro-motor functions. The analysis further indicates that speech and language pathologists should consider separate norms for clients of 65-74 years and those of 75-86 years. Hebrew rates were found to be different from English norms for the oldest group, shedding light on the impact of language on these norms. Finally, the data support using a dual-protocol (real- and non-word repetition) with older adults to improve differential diagnosis of normal and pathological ageing in this task.}, } @article {pmid27431462, year = {2016}, author = {Daugherty, EC and Daugherty, MR and Bogart, JA and Shapiro, A}, title = {Adjuvant Radiation Improves Survival in Older Women Following Breast-Conserving Surgery for Estrogen Receptor-Negative Breast Cancer.}, journal = {Clinical breast cancer}, volume = {16}, number = {6}, pages = {500-506.e2}, doi = {10.1016/j.clbc.2016.06.017}, pmid = {27431462}, issn = {1938-0666}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/*radiotherapy/surgery ; Combined Modality Therapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptors, Estrogen/metabolism ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE: Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen receptor-positive (ER[+]) breast cancer. As the population with ER[-] tumors may be at greater risk for relapse, particularly given that endocrine therapy is not effective, we hypothesize the addition of radiation would be of benefit in patients age ≥ 70.

METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast-conserving surgery for T1, ER[-] invasive ductal carcinoma. Patients were separated into 2 cohorts: those treated with and without adjuvant radiotherapy. Chi-square analysis, unpaired t test and Kaplan-Meier log-rank were used to compare patient and tumor characteristics as well as overall and cancer-specific survival between the cohorts.

RESULTS: Overall, 3685 patients received radiation and 1493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 vs. 78 years, P < .0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (P < .0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (P < .0001).

CONCLUSIONS: This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER[-], early-stage breast cancer have improved overall survival and breast cancer-specific survival compared with patients treated with lumpectomy alone. This information may help in the decision-making process for this patient population.}, } @article {pmid27431459, year = {2016}, author = {Bufi, E and Belli, P and Di Matteo, M and Giuliani, M and Tumino, M and Rinaldi, P and Nardone, L and Franceschini, G and Mulé, A and Bonomo, L}, title = {Hypervascularity Predicts Complete Pathologic Response to Chemotherapy and Late Outcomes in Breast Cancer.}, journal = {Clinical breast cancer}, volume = {16}, number = {6}, pages = {e193-e201}, doi = {10.1016/j.clbc.2016.06.007}, pmid = {27431459}, issn = {1938-0666}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biopsy, Large-Core Needle ; Breast/*blood supply/diagnostic imaging/pathology ; Breast Neoplasms/*blood supply/*drug therapy/mortality/pathology ; Carcinoma, Ductal, Breast/*blood supply/*drug therapy/mortality/pathology ; Contrast Media/administration & dosage ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Magnetic Resonance Angiography ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoplasm Recurrence, Local/blood supply/*epidemiology/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Our objective was to investigate the relationship between asymmetric increase in breast vascularity (AIBV) and pathologic profiles of breast cancer. We also addressed the prognostic performance of AIBV and of vascular maps reduction after neoadjuvant chemotherapy (NAC) in predicting pathologic complete response (pCR) at surgery and outcome at follow-up.

MATERIALS AND METHODS: Two hundred nineteen patients with unilateral locally advanced breast cancer (LABC) underwent magnetic resonance imaging before and after NAC. Axial, sagittal, and coronal maximum intensity projections were obtained in a subjective comparative evaluation. Asymmetrical versus symmetrical breast vascularity was defined through number of vessels, diameter, and signal intensity. Kaplan-Meier methodology was employed for late survival (31.4 ± 18 months follow-up).

RESULTS: AIBV ipsilateral to LABC occurred in 62.5% (P < .001). AIBV was significantly associated with invasive ductal carcinoma, G3, triple-negative, HER2+, and hybrid phenotypes (P < .001). pCR was more frequent among patients with AIBV (24%) (P = .001). After NAC, the vascular map was significantly reduced, particularly in patients with pCR (P < .001). At follow-up, the recurrence rate was 22% (6.1% mortality). AIBV after NAC was associated with worse late survival (P = .036). A trend towards worse late survival existed among patients with AIBV before NAC. We did not observe statistically different survival according to the variation of vascularity after NAC.

CONCLUSION: LABC with ipsilateral AIBV before NAC is associated with more aggressive pathologic profiles. Nonetheless, it is more sensitive to NAC and shows a higher frequency of pCR. The persistence of AIBV after NAC entails a worse late prognosis and should prompt more aggressive therapeutic strategies.}, } @article {pmid27430170, year = {2016}, author = {Liu, L and Li, D and Chen, S and Zhao, R and Pang, D and Li, D and Fu, Z}, title = {B7-H4 expression in human infiltrating ductal carcinoma‑associated macrophages.}, journal = {Molecular medicine reports}, volume = {14}, number = {3}, pages = {2135-2142}, doi = {10.3892/mmr.2016.5510}, pmid = {27430170}, issn = {1791-3004}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/immunology/*metabolism/*pathology ; Carcinoma, Ductal, Breast/immunology/*metabolism/*pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Macrophages/immunology/*metabolism/pathology ; Middle Aged ; Neoplasm Staging ; Phenotype ; Tumor Microenvironment ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/genetics/*metabolism ; }, abstract = {B7-H4 is a co‑inhibitory molecule of the B7 family, which is expressed on antigen‑presenting cells (APCs) and is able to limit the T‑cell immune response. Macrophages act as professional APCs and are important for immunoregulation of the tumor microenvironment in breast cancer. In order to identify the association between the presence of B7‑H4 on macrophages and infiltrating ductal carcinoma (IDC), the present study investigated the expression of B7‑H4 on macrophages with different polarizations. The expression levels of B7‑H4 in IDC tissues were determined using immunohistochemistry, and the expression of B7‑H4 on macrophages in the breast IDC microenvironment were determined using western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression levels of interleukin (IL)‑6 and IL‑10 were detected in IDC tissues and the supernatants of polarized macrophages using an enzyme‑linked immunosorbent assay and RT‑qPCR. The present study demonstrated that B7‑H4 was overexpressed in IDC tissues and macrophages. In vitro, M1 and M2 macrophages exhibited different expression levels of B7‑H4. IL‑6 and ‑10 exhibited higher expression in the IDC tissues compared with in distal pericarcinomatous tissues. In conclusion, B7‑H4 exhibited overexpression in IDC tissues and cultured macrophage cells. Furthermore, M2 macrophages exhibited higher expression levels of B7‑H4 compared with the M1 subtype. In addition, IL‑6 and ‑10 may be associated with B7‑H4 expression on macrophages of different polarizations in the IDC microenvironment.}, } @article {pmid27425567, year = {2016}, author = {Shoshani, A and Steinmetz, S and Kanat-Maymon, Y}, title = {Effects of the Maytiv positive psychology school program on early adolescents' well-being, engagement, and achievement.}, journal = {Journal of school psychology}, volume = {57}, number = {}, pages = {73-92}, doi = {10.1016/j.jsp.2016.05.003}, pmid = {27425567}, issn = {1873-3506}, mesh = {*Achievement ; Adolescent ; *Emotions ; Female ; Humans ; Longitudinal Studies ; Male ; *Outcome Assessment, Health Care ; *Personal Satisfaction ; Psychology, Educational/*methods ; *Schools ; Students/*psychology ; }, abstract = {As positive psychology is a nascent area of research, there are very few empirical studies assessing the impact and sustained effects of positive psychology school interventions. The current study presents a 2-year longitudinal evaluation of the effects of a school-based positive psychology program on students' subjective well-being, school engagement, and academic achievements. The study investigated the effectiveness of the Maytiv school program using a positive psychology-based classroom-level intervention with 2517 seventh- to ninth-grade students in 70 classrooms, from six schools in the center of Israel. The classes were randomly assigned to intervention and control conditions, which were comparable in terms of students' age, gender, and socio-economic status. Hierarchical linear regression analyses revealed positive intervention effects on positive emotions, peer relations, emotional engagement in school, cognitive engagement, and grade point average scores (Cohen's ds 0.16-0.71). In the control group, there were significant decreases in positive emotions and cognitive engagement, and no significant changes in peer relations, emotional engagement or school achievements. These findings demonstrate the significant socio-emotional and academic benefits of incorporating components of positive psychology into school curricula.}, } @article {pmid27423582, year = {2016}, author = {Santangelo, G and Falco, F and D'Iorio, A and Cuoco, S and Raimo, S and Amboni, M and Pellecchia, MT and Longo, K and Vitale, C and Barone, P}, title = {Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).}, journal = {Journal of the neurological sciences}, volume = {367}, number = {}, pages = {158-161}, doi = {10.1016/j.jns.2016.06.008}, pmid = {27423582}, issn = {1878-5883}, mesh = {Aged ; Anxiety/*diagnosis/epidemiology ; Depression/diagnosis/epidemiology ; Female ; Humans ; Male ; Neuropsychological Tests ; Parkinson Disease/*diagnosis/epidemiology/*psychology ; Prevalence ; *Psychiatric Status Rating Scales ; Psychometrics ; ROC Curve ; Reproducibility of Results ; Translating ; }, abstract = {INTRODUCTION: Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients.

METHODS: A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales.

RESULTS: There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%).

CONCLUSION: The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages.}, } @article {pmid27421080, year = {2017}, author = {Stahl, V and Maier, F and Freitag, MT and Floca, RO and Berger, MC and Umathum, R and Berriel Diaz, M and Herzig, S and Weber, MA and Dimitrakopoulou-Strauss, A and Rink, K and Bachert, P and Ladd, ME and Nagel, AM}, title = {In vivo assessment of cold stimulation effects on the fat fraction of brown adipose tissue using DIXON MRI.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {45}, number = {2}, pages = {369-380}, doi = {10.1002/jmri.25364}, pmid = {27421080}, issn = {1522-2586}, mesh = {Adipose Tissue, Brown/*anatomy & histology/*physiology ; Adiposity/*physiology ; Adult ; Algorithms ; Body Temperature/physiology ; *Cold Temperature ; Cold-Shock Response/*physiology ; Female ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Organ Size ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To evaluate the volume and changes of human brown adipose tissue (BAT) in vivo following exposure to cold using magnetic resonance imaging (MRI).

MATERIALS AND METHODS: The clavicular region of 10 healthy volunteers was examined with a 3T MRI system. One volunteer participated twice. A cooling vest that was circulated with temperature-controlled water was used to expose each volunteer to a cold environment. Three different water temperature phases were employed: baseline (23°C, 20 min), cooling (12°C, 90 min), and a final warming phase (37°C, 30 min). Temperatures of the water in the circuit, of the body, and at the back skin of the volunteers were monitored with fiberoptic temperature probes. Applying the 2-point DIXON pulse sequence every 5 minutes, fat fraction (FF) maps were determined and evaluated over time to distinguish between brown and white adipose tissue.

RESULTS: Temperature measurements showed a decrease of 3.8 ± 1.0°C of the back skin temperature, while the body temperature stayed constant at 37.2 ± 0.9°C. Focusing on the two interscapular BAT depots, a mean FF decrease of -2.9 ± 2.0%/h (P < 0.001) was detected during cold stimulation in a mean absolute volume of 1.31 ± 1.43 ml. Also, a correlation of FF decrease to back skin temperature decrease was observed in all volunteers (correlation coefficients: |r| = [0.51; 0.99]).

CONCLUSION: We found that FF decreases in BAT begin immediately with mild cooling of the body and continue during long-time cooling.

LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:369-380.}, } @article {pmid27415582, year = {2016}, author = {Laudanski, K and Zawadka, M and Lapko, N}, title = {The Ability of Precursory Monocytes (MO) to Differentiate Varies Among Individuals But Is Stable Over Time.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {22}, number = {}, pages = {2463-2470}, pmid = {27415582}, issn = {1643-3750}, mesh = {Adult ; Antigens, CD1/immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/cytology/immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Humans ; Interleukin-4/immunology ; Lymphocyte Culture Test, Mixed ; Macrophage Colony-Stimulating Factor/immunology ; Macrophages/cytology/immunology ; Male ; Middle Aged ; Monocytes/*cytology/immunology ; T-Lymphocytes/cytology/immunology ; }, abstract = {BACKGROUND The ability to generate dendritic cells (DCs) from precursory monocytes (MOs) was a breakthrough in the field of immunology. However, it is unknown whether the ability of MOs to differentiate into immature DCs (iDCs) differs across subjects or is time dependent. Given that the study of immune system function is gaining recognition in the field of clinical medicine, it is important to know how certain immunologic features vary over time. MATERIAL AND METHODS This study investigates how much individuals' MO-to-iDC differentiation potential changes over time. We estimated this potential by measuring the expression of an iDC marker (CD1a), cytokine secretion (interleukin [IL]-12p70), and the ability of IL-4 and granulocyte macrophage colony-stimulating factor (GM-CSF) differentiation MOs to stimulate T cells. We collected MOs obtained from different subjects (n=17) at least 1 month apart. Furthermore, we investigated several variables (expression for cytokine receptors, timing, and emergence of DC-related transcriptional factor PU.1). RESULTS The ability of MOs to become DCs under the influence of IL-4 and GM-CSF varied greatly between individuals (range of CD1a expression, 20-80%) but was stable over time (change of CD1a expression between sampling, ~5%). A similar pattern emerged when production of IL-12p70 was analyzed. The ability to stimulate T cells was variable and depended on the T-cell source. The ability of MOs to become iDCs was not linked to the surface expression of receptors for IL-4 and GM-CSF but rather to the activation of PU.1 in the precursory MO. It took 5 days for all committed MOs to become iDCs under in vitro influence of IL-4 and GM-CSF. CONCLUSIONS We concluded that the potential of MO to become iDC is an individual feature and depends on activation of PU.1.}, } @article {pmid27409620, year = {2016}, author = {Khan, MR and Kang, SW}, title = {Highly Sensitive Temperature Sensors Based on Fiber-Optic PWM and Capacitance Variation Using Thermochromic Sensing Membrane.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {27409620}, issn = {1424-8220}, abstract = {In this paper, we propose a temperature/thermal sensor that contains a Rhodamine-B sensing membrane. We applied two different sensing methods, namely, fiber-optic pulse width modulation (PWM) and an interdigitated capacitor (IDC)-based temperature sensor to measure the temperature from 5 °C to 100 °C. To the best of our knowledge, the fiber-optic PWM-based temperature sensor is reported for the first time in this study. The proposed fiber-optic PWM temperature sensor has good sensing ability; its sensitivity is ~3.733 mV/°C. The designed temperature-sensing system offers stable sensing responses over a wide dynamic range, good reproducibility properties with a relative standard deviation (RSD) of ~0.021, and the capacity for a linear sensing response with a correlation coefficient of R[2] ≈ 0.992 over a wide sensing range. In our study, we also developed an IDC temperature sensor that is based on the capacitance variation principle as the IDC sensing element is heated. We compared the performance of the proposed temperature-sensing systems with different fiber-optic temperature sensors (which are based on the fiber-optic wavelength shift method, the long grating fiber-optic Sagnac loop, and probe type fiber-optics) in terms of sensitivity, dynamic range, and linearity. We observed that the proposed sensing systems have better sensing performance than the above-mentioned sensing system.}, } @article {pmid27408713, year = {2016}, author = {Staruch, RM and Rouhani, MJ and Ellabban, M}, title = {The surgical management of male breast cancer: Time for an easy access national reporting database?.}, journal = {Annals of medicine and surgery (2012)}, volume = {9}, number = {}, pages = {41-49}, pmid = {27408713}, issn = {2049-0801}, abstract = {INTRODUCTION: Male breast cancer is extremely rare with an incidence of less than 1% of all breast cancers. Literature reports a peak of incidence at roughly 71 years of age. Management currently follows the same clinical pathways as female breast cancer as a general rule.

METHODS: A retrospective search for all patients who were referred and diagnosed with male breast cancer at our centre was undertaken. Patients notes were then explored for demographics, histological staging, multidisciplinary team meeting outcome and treatment. A literature search including the search terms 'Male Breast Cancer AND Surgery' or 'Male Breast Cancer AND Experience' were used. Non English language articles, or those without abstracts were excluded.

RESULTS: Seven patients were reviewed over 3 years (2006-2009). Mean agea was 69 years and mean lesion size was 15 mm. Histology was invasive ductal carcinoma for all patients. All patients were ER receptor positive. Two patients were HER2 positive. Five patients were offered mastectomy. One patient refused treatment. In follow up at 36 months there were 3 recurrences. 1 patient was lost to follow up. There were 3 mortalities. The literature search identified 72 articles. Articles were subdivided into those that discussed the surgical management of male breast cancer (n = 8), articles that discussed male breast cancer as podium presentations or posters with no full text article publication (n = 13) and finally full text publications of case experience of male breast cancer (n = 21).

DISCUSSION: We report a series of seven cases of male breast cancer encountered over three years, evaluating patient demographics as well as treatment and outcomes. In our series patients were managed with mastectomy. New evidence is questioning the role of mastectomy against breast conserving surgery in male patients. Furthermore there is a lack of reporting infrastructure for national data capture of the benefits of surgical modalities. Literature review highlights the varied clinical experience between units that remains reported as podium presentation but not published. The establishment of an online international reporting registry would allow for efficient analysis of surgical outcomes to improve patient care from smaller single centres. This would facilitate large scale meta analysis by larger academic surgical centres.}, } @article {pmid27404457, year = {2016}, author = {Lumachi, F and Basso, SM and Camozzi, V and Tozzoli, R and Spaziante, R and Ermani, M}, title = {Bone turnover markers in women with early stage breast cancer who developed bone metastases. A prospective study with multivariate logistic regression analysis of accuracy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {460}, number = {}, pages = {227-230}, doi = {10.1016/j.cca.2016.07.005}, pmid = {27404457}, issn = {1873-3492}, mesh = {Aged ; Alkaline Phosphatase/analysis ; Biomarkers, Tumor/analysis ; Bone Neoplasms/diagnosis/*secondary ; *Bone Remodeling ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Peptide Fragments/analysis ; Postmenopause ; Procollagen/analysis ; Prospective Studies ; Tartrate-Resistant Acid Phosphatase/analysis ; }, abstract = {BACKGROUND: The skeleton is the most common site of metastasis for breast cancer and the periodic measurement of circulating bone turnover markers (BTMs) can be useful. The aim of this study was to prospectively evaluate the diagnostic accuracy of a panel of BTMs in the early detection of bone metastases (BMs).

METHODS: We reviewed the medical records of 297 postmenopausal women with early stage luminal-type invasive ductal carcinoma (IDC). Twenty-six patients who developed isolated BMs during follow-up and 24 randomly selected controls were studied. The two groups were matched according to age, final disease staging, and follow-up. All patients underwent periodic measurement of total and bone-specific (BSAP) alkaline phosphatase, CTX, ICTP, osteocalcin, NTX, PINP, and TRACP5b.

RESULTS: Only BSAP, CTX, PINP, and TRACP5b were significantly (p<0.05) associated with the group, and the logistic regression analysis excluded CTX from the model. The AUC (ROC curve) for TRACP5b alone, which was the most accurate marker, and for the combination of BSAP+PINP+TRACP5b was 0.784 (95% CI: 0.651-0.916) and 0.889 (95% CI: 0.798-0.981), respectively.

CONCLUSION: According to our results, the measurement of these three markers together should be performed in all postmenopausal patients with luminal-type IDC, when an early diagnosis of BMs is required.}, } @article {pmid27401634, year = {2016}, author = {Divatia, MK and Ro, JY}, title = {Intraductal Carcinoma of the Prostate Gland: Recent Advances.}, journal = {Yonsei medical journal}, volume = {57}, number = {5}, pages = {1054-1062}, pmid = {27401634}, issn = {1976-2437}, mesh = {Carcinoma, Acinar Cell/chemistry/*diagnosis/pathology ; Carcinoma, Ductal/chemistry/*diagnosis/pathology ; Carcinoma, Transitional Cell/chemistry/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Male ; Neoplasm Grading ; Prostatic Intraepithelial Neoplasia/chemistry/*diagnosis/pathology ; Prostatic Neoplasms/chemically induced/*diagnosis/*pathology ; Tumor Burden ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up.}, } @article {pmid27401580, year = {2016}, author = {Turner, RB and Valcarlos, E and Won, R and Chang, E and Schwartz, J}, title = {Impact of Infectious Diseases Consultation on Clinical Outcomes of Patients with Staphylococcus aureus Bacteremia in a Community Health System.}, journal = {Antimicrobial agents and chemotherapy}, volume = {60}, number = {10}, pages = {5682-5687}, pmid = {27401580}, issn = {1098-6596}, mesh = {Adult ; Aged ; Bacteremia/*drug therapy/mortality ; Cohort Studies ; Community Health Services ; Female ; Hospitals ; Humans ; Male ; Middle Aged ; Mortality ; Oregon ; Quality of Health Care ; Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/*drug therapy/mortality ; Staphylococcus aureus/*pathogenicity ; Treatment Outcome ; }, abstract = {Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited settings such as community hospitals are available. This retrospective cohort study evaluated the adherence to quality-of-care indicators and the clinical outcomes for SAB in a five-hospital community health system (range of 95 to 272 available beds per hospital), for patients with versus without infectious diseases consultation (IDC). IDC was provided if requested by the attending physician. The primary outcome was the incidence of treatment failure, defined as 30-day in-hospital death or 90-day SAB recurrence. Other outcomes included adherence to quality-of-care indicators. A total of 473 adult patients with SAB were included, with 369 (78%) receiving IDC. We identified substantial differences in baseline characteristics between the IDC group and the no-IDC group, including greater incidences of complicated bacteremia and intravenous drug users in the IDC group, with similar rates of severe illness (measured by Pitt bacteremia scores). Adherence to quality-of-care indicators was greater for patients with IDC (P < 0.001). After adjustment for other predicting variables, IDC was associated with a lower rate of treatment failure (adjusted odds ratio, 0.42 [95% confidence interval, 0.20 to 0.86]; P = 0.018). IDC provided better quality of care and better clinical outcomes for patients with SAB who were treated at small, resource-limited, community hospitals.}, } @article {pmid27400309, year = {2016}, author = {Xie, X and Wu, B and Chen, Y and Li, W and Hu, X and Chen, J}, title = {Peripheral endothelial function may predict the effectiveness of beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {International journal of cardiology}, volume = {221}, number = {}, pages = {128-133}, doi = {10.1016/j.ijcard.2016.06.164}, pmid = {27400309}, issn = {1874-1754}, mesh = {Adrenergic beta-Antagonists/pharmacology ; Adult ; Aged ; *Cardiomyopathy, Dilated/diagnosis/drug therapy/physiopathology ; Drug Monitoring/methods ; Echocardiography/methods ; *Endothelium, Vascular/drug effects/pathology/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Treatment Outcome ; Ventricular Dysfunction, Left/diagnosis/physiopathology/*prevention & control ; Ventricular Function, Left/*drug effects/physiology ; Ventricular Remodeling/*drug effects/physiology ; }, abstract = {OBJECTIVES: Beta-blockers have improved the prognosis of patients with dilated cardiomyopathy as they improve left ventricular (LV) systolic function and structure, which are crucial for myocardial recovery. However, to date, no accurate methods can predict the effectiveness of β-blocker therapy. Our goal was to evaluate whether peripheral endothelial function could be a useful predictor for β-blocker responses and related LV reverse remodeling (LVRR) in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS: Fifty-two IDC patients were recruited and underwent brachial artery flow-mediated dilation (FMD). Beta-blockers were titrated to doses tolerable for each patient. LV function and structure were measured by echocardiography. A positive response to β-blockers was defined as an increase of ≥10% in LV ejection fraction (LVEF). LVRR was defined as an increase of ≥10% in LVEF and a decrease of ≥15% in LV end-systolic volume (LVESV).

RESULTS: Baseline FMD was 8.4±3.0% in IDC patients and significantly lower than healthy controls. At three-month follow-up, 54% of patients had a positive β-blocker response and 40% achieved LVRR. Patients with a positive response to β-blockers or with LVRR had significantly higher baseline FMD values than those without. FMD was the most significant predictor of changes in LVEF and LVESV. The sensitivity and specificity of baseline FMD to predict β-blocker responses was 64.3% and 83.3%, respectively, and to predict LVRR was 61.9% and 80.6%, respectively. Beta-blockers themselves did not influence FMD values.

CONCLUSIONS: FMD could serve as an independent predictor for monitoring β-blocker therapy effectiveness in IDC patients.}, } @article {pmid27399250, year = {2016}, author = {Birnbaum, GE and Reis, HT and Mizrahi, M and Kanat-Maymon, Y and Sass, O and Granovski-Milner, C}, title = {Intimately connected: The importance of partner responsiveness for experiencing sexual desire.}, journal = {Journal of personality and social psychology}, volume = {111}, number = {4}, pages = {530-546}, doi = {10.1037/pspi0000069}, pmid = {27399250}, issn = {1939-1315}, mesh = {Adult ; Female ; Humans ; *Interpersonal Relations ; Male ; Sexual Behavior/*psychology ; Sexual Partners/*psychology ; Spouses/*psychology ; Young Adult ; }, abstract = {Sexual desire tends to subside gradually over time, with many couples failing to maintain desire in their long-term relationships. Three studies employed complementary methodologies to examine whether partner responsiveness, an intimacy-building behavior, could instill desire for one's partner. In Study 1, participants were led to believe that they would interact online with their partner. In reality, they interacted with either a responsive or an unresponsive confederate. In Study 2, participants interacted face-to-face with their partner, and judges coded their displays of responsiveness and sexual desire. Study 3 used a daily experiences methodology to examine the mechanisms underlying the responsiveness-desire linkage. Overall, responsiveness was associated with increased desire, but more strongly in women. Feeling special and perceived partner mate value explained the responsiveness-desire link, suggesting that responsive partners were seen as making one feel valued as well as better potential mates for anyone and thus as more sexually desirable. (PsycINFO Database Record}, } @article {pmid27399228, year = {2016}, author = {Ingla-Aynés, J and Meijerink, RJ and Wees, BJ}, title = {Eighty-Eight Percent Directional Guiding of Spin Currents with 90 μm Relaxation Length in Bilayer Graphene Using Carrier Drift.}, journal = {Nano letters}, volume = {16}, number = {8}, pages = {4825-4830}, doi = {10.1021/acs.nanolett.6b01004}, pmid = {27399228}, issn = {1530-6992}, abstract = {Electrical control of spin signals and long distance spin transport are major requirements in the field of spin electronics. Here, we report the efficient guiding of spin currents at room temperature in high mobility hexagonal boron nitride encapsulated bilayer graphene using carrier drift. Our experiments, together with modeling, show that the spin relaxation length, that is 7.7 μm at zero bias, can be tuned from 0.6 to 90 μm when applying a DC current of ∓90 μA, respectively. Our results also show that we are able to direct spin currents to either side of a spin injection contact. Eighty-eight percent of the injected spins flows to the left when Idc = -90 μA and eighty-two percent flows to the right when the drift current is reversed. These results show the potential of carrier drift for spin-based logic operations and devices.}, } @article {pmid27399100, year = {2016}, author = {Hahn, SY and Ko, ES and Han, BK and Lim, Y and Gu, S and Ko, EY}, title = {Analysis of factors influencing the degree of detectability on diffusion-weighted MRI and diffusion background signals in patients with invasive breast cancer.}, journal = {Medicine}, volume = {95}, number = {27}, pages = {e4086}, pmid = {27399100}, issn = {1536-5964}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/methods ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {To determine the factors influencing the degree of detectability of lesions and diffusion background signals on magnetic resonance diffusion-weighted imaging (DWI) in invasive breast cancer.Institutional review board approval was obtained and patient consent was waived. Patients with newly diagnosed invasive ductal carcinoma, who underwent preoperative breast magnetic resonance imaging with DWI were included in this study (n = 167). Lesion detectability on DWI and contrast-enhanced subtracted T1-weighted images, the degree of background parenchymal enhancement (BPE), and diffusion background signal were qualitatively rated. Detectability of lesions on DWI was compared with clinicopathological findings including menopausal status, mammographic density, and molecular subtype of breast cancer. Multivariate linear regression analysis was performed to determine variables independently associated with detectability of lesions on DWI and diffusion background signals.Univariate analysis showed that the detectability of lesions on DWI was significantly associated with lesion size (P = 0.001), diffuse background signal (P < 0.0001), and higher detectability scores for contrast-enhanced T1-weighted subtraction images (P = 0.000). The degree of diffusion background signal was significantly affected by age (P < 0.0001), BPE (P < 0.0001), mammographic density (P = 0.002), and menopausal status (P < 0.0001). On multivariate analysis, the diffusion background signal (P < 0.0001) and histologic grade (P < 0.0001) were correlated with the detectability on DWI of invasive breast cancer. Only BPE was correlated with the amount of diffusion background signal on DWI (P < 0.0001).For invasive breast cancers, detectability on DWI was significantly affected by the diffusion background signal. BPE, menopausal status, menstrual cycle, or mammographic density did not show statistically significant correlation with the diffusion detectability of lesions on DWI.}, } @article {pmid27383477, year = {2016}, author = {Sopik, V and Iqbal, J and Sun, P and Narod, SA}, title = {Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {158}, number = {2}, pages = {385-393}, doi = {10.1007/s10549-016-3894-9}, pmid = {27383477}, issn = {1573-7217}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology ; Carcinoma, Ductal, Breast/*diagnosis/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/epidemiology ; Child ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; SEER Program ; Survival Analysis ; Young Adult ; }, abstract = {A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same way.}, } @article {pmid27382391, year = {2016}, author = {Kim, EY and Do, SI and Hyun, K and Park, YL and Kim, DH and Chae, SW and Sohn, JH and Park, CH}, title = {High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast.}, journal = {Journal of breast cancer}, volume = {19}, number = {2}, pages = {156-162}, pmid = {27382391}, issn = {1738-6756}, abstract = {PURPOSE: In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer.

METHODS: Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen.

RESULTS: Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001).

CONCLUSION: Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC.}, } @article {pmid27382390, year = {2016}, author = {Damavandi, Z and Torkashvand, S and Vasei, M and Soltani, BM and Tavallaei, M and Mowla, SJ}, title = {Aberrant Expression of Breast Development-Related MicroRNAs, miR-22, miR-132, and miR-212, in Breast Tumor Tissues.}, journal = {Journal of breast cancer}, volume = {19}, number = {2}, pages = {148-155}, pmid = {27382390}, issn = {1738-6756}, abstract = {PURPOSE: MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that posttranscriptionally regulate the expression of most genes in the human genome. miRNAs are often located in chromosomal fragile sites, which are suscept-ible to amplification or deletion. Chromosomal deletions are frequent events in breast cancer cells. Deletion and loss of heterozygosity at 17p13.3 have been reported in 49% of breast cancers. The aim of the current study was to evaluate potential expression alterations of miR-22, miR-132, and miR-212, which are located on the 17p13.3 locus and are required for mammary gland development.

METHODS: A matched case-control study was conducted, which included 36 pairs of tumor and matched nontumor surgical specimens from patients diagnosed with breast invasive ductal carcinoma. Formalin-fixed paraffin-embedded samples from archival collections at the pathology department of Shariati Hospital were prepared for RNA extraction using the xylene-ethanol method before total RNA was isolated with TRIzol Reagent. Specific primers were designed for cDNA synthesis and miRNA amplification. The expression of miRNAs was then evaluated by real-time polymerase chain reaction (RT-PCR).

RESULTS: According to our RT-PCR data, the miR-212/miR-132 family was downregulated in breast cancer (0.328-fold, p<0.001), and this reduced expression was the most prominent in high-grade tumors. In contrast, miR-22 exhibited a significant upregulation in breast tumor samples (2.183-fold, p=0.040).

CONCLUSION: Consistent with the frequent deletion of the 17p13.3 locus in breast tumor cells, our gene expression data demonstrated a significant downregulation of miR-212 and miR-132 in breast cancer tissues. In contrast, we observed a significant upregulation of miR-22 in breast tumor samples. The latter conflicting result may have been due to the upregulation of miR-22 in stromal/cancer-associated fibroblasts, rather than in the tumor cells.}, } @article {pmid27382389, year = {2016}, author = {Choi, J and Kim, DI and Kim, J and Kim, BH and Kim, A}, title = {Hornerin Is Involved in Breast Cancer Progression.}, journal = {Journal of breast cancer}, volume = {19}, number = {2}, pages = {142-147}, pmid = {27382389}, issn = {1738-6756}, abstract = {PURPOSE: The S100 gene family, which comprises over 20 members, including S100A1, S100A2, S100A8, S100A9, profilaggrin, and hornerin encodes low molecular weight calcium-binding proteins with physiological and pathological roles in keratinization. Recent studies have suggested a link between S100 proteins and human cancer progression. The purpose of the present study was to determine the expression levels of hornerin, S100A8, and S100A9 and evaluate their roles in the progression of invasive ductal carcinoma (IDC).

METHODS: Seventy cases of ductal carcinoma in situ (DCIS), IDC, and metastatic carcinoma in lymph nodes (MCN) were included. Tissue microarrays were constructed from lesions of DCIS, IDC, and MCN from the same patients. Expression of hornerin, S100A8, and S100A9 was analyzed using immunohistochemistry.

RESULTS: The expression of hornerin was associated with the estrogen receptor-negative (p=0.003) and the human epidermal growth factor receptor 2-positive (p=0.002) groups. The expression of S100A8 was associated with a higher pT stage (p=0.017). A significant (p<0.001) correlation between the expression of S100A9 and S100A8 was also found. The mean percentages of hornerin-positive tumor cells in DCIS, IDC, and MCN were 1.0%±3.3% (mean±standard deviation), 12.0%±24.0%, and 75.3%± 27.6%, respectively. The expression of hornerin significantly (p<0.001) increased with the progression of carcinoma. The mean levels of S100A8 and S100A9 in DCIS, IDC, and MCN were not significantly (p>0.050) different. The expression of hornerin increased in a stepwise manner (DCIS
CONCLUSION: Our data suggest that hornerin is involved in breast cancer progression and malignant transformation from preinvasive lesions.}, } @article {pmid27382388, year = {2016}, author = {Ali, A and Ullah, F and Ali, IS and Faraz, A and Khan, M and Shah, ST and Ali, N and Saeed, M}, title = {Aberrant Promoter Methylation at CpG Cytosines Induce the Upregulation of the E2F5 Gene in Breast Cancer.}, journal = {Journal of breast cancer}, volume = {19}, number = {2}, pages = {133-141}, pmid = {27382388}, issn = {1738-6756}, abstract = {PURPOSE: The promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology.

METHODS: The promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR® green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed.

RESULTS: Significant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Δmeth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%).

CONCLUSION: Methylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer.}, } @article {pmid27376491, year = {2016}, author = {Koca, İ and Özgür, A and Er, M and Gümüş, M and Açikalin Coşkun, K and Tutar, Y}, title = {Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis.}, journal = {European journal of medicinal chemistry}, volume = {122}, number = {}, pages = {280-290}, doi = {10.1016/j.ejmech.2016.06.032}, pmid = {27376491}, issn = {1768-3254}, mesh = {Adenosine Triphosphatases/antagonists & inhibitors ; Adenosine Triphosphate/metabolism ; Antineoplastic Agents/chemical synthesis/chemistry/pharmacology ; Bone Neoplasms/pathology/*secondary ; Carcinoma, Ductal, Breast/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Drug Design ; HSP90 Heat-Shock Proteins/*antagonists & inhibitors/chemistry ; Humans ; Hydrolysis/drug effects ; Molecular Docking Simulation ; Protein Conformation, beta-Strand ; Thiourea/*chemical synthesis/chemistry/*pharmacology ; }, abstract = {Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 μM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as well as new therapeutic perspective for drug design.}, } @article {pmid27375937, year = {2016}, author = {Zhao, Y and Pogue, BW and Haider, SJ and Gui, J and diFlorio-Alexander, RM and Paulsen, KD and Jiang, S}, title = {Portable, parallel 9-wavelength near-infrared spectral tomography (NIRST) system for efficient characterization of breast cancer within the clinical oncology infusion suite.}, journal = {Biomedical optics express}, volume = {7}, number = {6}, pages = {2186-2201}, pmid = {27375937}, issn = {2156-7085}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; R01 CA176086/CA/NCI NIH HHS/United States ; }, abstract = {A portable near-infrared spectral tomography (NIRST) system was developed with simultaneous frequency domain (FD) and continuous-wave (CW) optical measurements for efficient characterization of breast cancer in a clinical oncology setting. Simultaneous FD and CW recordings were implemented to speed up acquisition to 3 minutes for all 9 wavelengths, spanning a range from 661nm to 1064nm. An adjustable interface was designed to fit various breast sizes and shapes. Spatial images of oxy- and deoxy-hemoglobin, water, lipid, and scattering components were reconstructed using a 2D FEM approach. The system was tested on a group of 10 normal subjects, who were examined bilaterally and the recovered optical images were compared to radiographic breast density. Significantly higher total hemoglobin and water were estimated in the high density relative to low density groups. One patient with invasive ductal carcinoma was also examined and the cancer region was characterized as having a contrast ratio of 1.4 in total hemoglobin and 1.2 in water.}, } @article {pmid27374087, year = {2016}, author = {Duru, N and Gernapudi, R and Lo, PK and Yao, Y and Wolfson, B and Zhang, Y and Zhou, Q}, title = {Characterization of the CD49f+/CD44+/CD24- single-cell derived stem cell population in basal-like DCIS cells.}, journal = {Oncotarget}, volume = {7}, number = {30}, pages = {47511-47525}, pmid = {27374087}, issn = {1949-2553}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/etiology/*pathology ; CD24 Antigen/*analysis ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Cell Line, Tumor ; Cell Movement ; DNA Methylation ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Integrin alpha6/*analysis ; Mice ; Neoplastic Stem Cells/*pathology ; Octamer Transcription Factor-3/physiology ; SOXB1 Transcription Factors/physiology ; }, abstract = {The molecular mechanisms responsible for the Ductal Carcinoma in Situ (DCIS)-Invasive Ductal Carcinoma (IDC) transition have yet to be elucidated. Due to the lack of molecularly targeted therapies, basal-like DCIS has a high risk of recurrence and progression to invasive and metastatic cancers. In this study, by applying a novel single-cell clonogenic approach with the CD49f+/CD44+/CD24- surface markers, we characterized the aggressive clones that have enhanced self-renewal, migratory and invasive capacities derived from a human DCIS model cell line MCF10DCIS. The aggressive clones had elevated ALDH1 activity, lower global DNA methylation and increased expression of stem cell related genes, especially concurrent activation of SOX2/OCT4. In addition, we showed that the aggressive clones have increased expression of lincRNA-RoR and miR-10b compared to non-aggressive clones, which enhance their self-renewal and invasive abilities. Finally, we confirmed our in vitro results in vivo, demonstrating that aggressive clones were capable of forming tumors in nude mice, whereas non-aggressive clones were not. Our data suggest that lincRNA-RoR and miR10b could be used to distinguish aggressive clones from non-aggressive clones within the heterogeneous CD49f+/CD44+/CD24- DCIS population. Our findings also provide the foundation to develop new chemoprevention agents for DCIS-IDC transition.}, } @article {pmid27373807, year = {2017}, author = {Telles, T and Barroso, R and Figueiredo, P and Salgueiro, DF and Vilas-Boas, JP and Junior, OA}, title = {Effect of hand paddles and parachute on backstroke coordination and stroke parameters.}, journal = {Journal of sports sciences}, volume = {35}, number = {9}, pages = {906-911}, doi = {10.1080/02640414.2016.1201210}, pmid = {27373807}, issn = {1466-447X}, mesh = {Arm/*physiology ; Biomechanical Phenomena ; Hand/*physiology ; Humans ; Male ; Motor Skills/*physiology ; Resistance Training/*instrumentation/methods ; Sports Equipment ; Swimming/*physiology ; Young Adult ; }, abstract = {Hand paddles and parachutes have been used in order to overload swimmers, and consequently increase the propulsive force generation in swimming. However, their use may affect not only kinematical parameters (average speed, stroke length and stroke rate), but also time gaps between propulsive phases, assessed through the index of coordination (IdC). The objective of this study was to assess the effects of hand paddles and parachute use, isolated or combined, on kinematical parameters and coordination. Eleven swimmers (backstroke 50-m time: 29.16 ± 1.43 s) performed four 15-m trials in a randomised order at maximal intensity: (1) without implements (FREE), (2) with hand paddles (HPD), (3) with parachute (PCH) and (4) with hand paddles plus parachute (HPD+PCH). All trials were video-recorded (60 Hz) in order to assess average speed, stroke rate, stroke length, five stroke phases and index of coordination. When average swimming speed was compared to FREE, it was lower in PCH and HPD+PCH, and higher in HPD. Stroke rate decreased in all overloaded trials compared to FREE. The use of hand paddles and parachute increased and decreased stroke length, respectively. In addition, propulsive phase duration was increased when hand paddles were used, and time gaps shifted towards zero (no time gap), especially when hand paddles were combined with parachute. It is conceivable that the combined use of hand paddles and parachute, once allowing overloading both propulsive and resistive forces, provides a specific stimulus to improve muscle strength and propulsive continuity.}, } @article {pmid27366204, year = {2016}, author = {Mwakigonja, AR and Rabiel, H and Mbembati, NA and Lema, LE}, title = {The pattern of prognostic and risk indicators among women with breast cancer undergoing modified radical mastectomy in Dar es Salaam, Tanzania.}, journal = {Infectious agents and cancer}, volume = {11}, number = {}, pages = {28}, pmid = {27366204}, issn = {1750-9378}, abstract = {BACKGROUND: Breast cancer is the commonest female malignancy globally and the second (after uterine cervix) in sub-Saharan Africa including Tanzania. Prognostic indicators reportedly influence post-mastectomy adjuvant therapy by predicting risks on survival and recurrence although in Tanzania this data is lacking. Here, we evaluate the pattern of prognostic and risk indicators among women with breast cancer undergoing modified-radical-mastectomy (MRM) at Muhimbili National Hospital (MNH) and Tumaini Hospital (TH), Dar es Salaam, Tanzania.

METHODS: This hospital-based prospective cross-sectional study included female patients undergoing MRM from April 2011 to January 2012. Clinical stage I-III patients were enrolled after being scheduled for mastectomy. Patients with evidence of distant metastasis (stage IV) were excluded. Mastectomy and axillary lymph nodes biopsies were submitted to the Histopathology laboratory for grade, type, nodal and margins status. Data was collected using a structured questionnaire and analyzed using SPSS.

RESULTS: A total of 348 patients were admitted with breast cancer including 86 patients (with 16 from TH having similar demography and presentation) meeting inclusion criteria. Age-range at diagnosis was 28-79 years, mean 52.1 years. Most (89 %) attained menarche after 11 years. About 56 % were postmenopausal. The majority (78 %) were multiparous with positive family history in 14.1 and 37.6 % used hormonal contraceptives. About 27.1 % were social alcohol drinkers. The majority (61 %) had T4b disease, 75.6 % had positive axillary nodes including 42.7 % with 4-9 involved nodes (N2). The commonest (91.9 %) histological type was invasive ductal carcinoma. Lobular, medullary and mucinous carcinomas were rare. Most (83.7 %) of our patients presented with stage III and the rest stage II. Intermediate- and high-grade tumors accounted for 73.5 %. Following MRM, 25 % of our patients had positive surgical margins and similarly for the base.

CONCLUSIONS: Most of our breast cancer patients present with frequent risks including younger age, multiparity, hormonal contraceptives use, alcohol use and family history. Unfavourable prognostic indicators including late stages, large primary tumor size, skin infiltration, positive surgical margins, positive axillary lymph nodes and a high histological grade were associated. A sustainable screening program by self-examination to allow early diagnosis is needed to reduce morbidity and mortality from this cancer.}, } @article {pmid27365197, year = {2016}, author = {Zhang, Y and Mo, M and Li, JW and Zhou, Y and Wu, J and Yu, KD and Shen, ZZ and Shao, ZM and Liu, GY}, title = {Better predictive value of axillary lymph node (ALN) status after systemic therapy for operable HER2-overexpressing breast cancer: A single-institution retrospective study.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {42}, number = {8}, pages = {1146-1152}, doi = {10.1016/j.ejso.2016.05.039}, pmid = {27365197}, issn = {1532-2157}, mesh = {Adult ; Anthracyclines/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Prognosis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Sentinel Lymph Node Biopsy ; Taxoids/administration & dosage ; Trastuzumab/administration & dosage ; }, abstract = {BACKGROUND: Thresholds for using Preoperative Systemic Therapy (PreST) have decreased to include early breast cancer. This study investigates the predictive value of axillary lymph node (ALN) status before and after systemic therapy and discusses whether it is better to receive PreST first in operable HER2-overexpressing breast cancer patients.

METHODS: From January 2008 to June 2013 at Fudan University Shanghai Cancer Center, we identified 406 eligible female patients with stage II-IIIa, operable and pathologically confirmed HER2-overexpressing invasive ductal carcinoma. Of these patients, 269 underwent surgery first followed by chemotherapy plus trastuzumab (chemo-trastuzumab) (SurgFirst group), whereas 137 received systemic chemo-trastuzumab therapy first followed by surgery (STFirst group). Disease-free survival (DFS) and overall survival (OS) were evaluated according to different ALN statuses using the Kaplan-Meier method. Multivariate COX model analyses were also conducted.

RESULTS: The median follow-up time was 47 months (IQR: 37-60). Both ALN status and overall pathological complete remission (pCR) status were shown to be significant for the prediction of DFS (p = 0.001 and p = 0.005, respectively) and OS (p = 0.009 and p = 0.027, respectively) in the STFirst group. However, patients with positive ALN(s) did not experience significantly poorer survival compared with those with negative ALN in the SurgFirst group. The adjusted hazard ratios (HRs) for positive ALN status in the STFirst and SurgFirst groups were 6.66 (p = 0.001, 95%CI: 2.18-20.38) and 2.40 (p = 0.126, 95%CI: 0.78-7.34), respectively.

CONCLUSION: The ALN status after systemic chemo-trastuzumab therapy better predicts the survival outcome. We recommend the application of PreST followed by surgery in patients with operable HER2-overexpressing breast cancer.}, } @article {pmid29097884, year = {2016}, author = {Boulogianni, G and Chryssogonidis, I and Drevelegas, A}, title = {Diffusion weighted MRI and spectroscopy in invasive carcinoma of the breast at 3Tesla. Correlation with dynamic contrast enhancement and pathologic findings.}, journal = {Hippokratia}, volume = {20}, number = {3}, pages = {192-197}, pmid = {29097884}, issn = {1108-4189}, abstract = {BACKGROUND: The most common histological types of invasive breast carcinomas are the invasive ductal carcinoma (IDC) and the invasive lobular carcinoma (ILC). The purpose of our study was to evaluate the role of the diffusion-weighted imaging (DWI) and the in vivo proton magnetic resonance spectroscopy ([1]H-MRS) at 3 Tesla magnet in invasive breast cancer and correlate them with the dynamic contrast enhancement (DCE) and pathologic findings.

METHODS: We retrospectively studied at 3Tesla magnet the apparent diffusion coefficient (ADC) values, the detection of choline in the [1]H-MRS and the kinetic analyses obtained after DCE in 181 patients with histologically confirmed invasive breast carcinomas. Among these patients, 160 had IDC and 21 ILC. We used the DWI sequence with a b value of 1,000 mm[2]/sec for the calculation of the ADC value, the fat-suppressed point-resolved spectroscopy (PRESS) sequence in order to evaluate the existence of a choline peak in the spectrum and the T1W GRE FAT SAT VIBRANT sequence for the characterization of the kinetic curves. Finally, we correlated the pathologic type of invasive cancer, as well as the type of the kinetic curve with the ADC value and the detectability of choline resonance in the spectrum in each of the 181 patients.

RESULTS: The ADC values in the 158 out of 160 IDC patients, ranged from 0.5 x 10[-3] to 1.2 x 10[-3] mm[2]/sec, with 78.1 % having ADC value of 1 x 10[-3] mm[2]/sec. Regarding the [1]H-MRS, in 121 out of 160 IDC patients, choline was found in 72.3 %. The ADC values in the 21 ILC patients also ranged from 0.5 x 10[-3] to 1.2 x 10[-3] mm[2]/sec with 57.1 % having ADC value of 1 x 10[-3] mm[2]/sec. Regarding the [1]H-MRS, in 10 out of 21 ILC patients, detection of choline was positive in 60 % of them. In the 21 ILC patients, the kinetic analysis after the dynamic administration of contrast medium showed type I (persistent) curve in 4.3 %, type II (plateau) curve in 33.3 % and type III (washout) in 52.4 %. In the 158 IDC patients (missing in two cases) type I curve was obtained in 0.63 %, type II in 19.4 % and type III in 80 %. From the correlation analysis of the IDC results using Kruskal-Wallis Test and the non-parametric Kendall's tau-b test, the curve type was positively associated (Kendal tau-b: 0.254, p =0.005) with the presence of choline, while the ADC value was negatively associated (Kendal tau-b: -0.224, p =0.011) with the presence of choline. In the ILC cases, the sample was insufficient for the correlation to become statistically significant. However, the ADC values tended to be lower in IDC patients (78.1 % having ADC value 1 x 10[-3] mm[2]/sec) compared to ILC (57.1 % having ADC value 1 x 10[-3] mm[2]/sec). Choline was more commonly detected in the IDC (72.3 %) than ILC (60 %) patients.

CONCLUSION: Our results are consistent with previous findings that both ADC values and choline detection in the spectrum play a significant role in establishing the final diagnosis of malignancy, especially when the kinetic pattern of enhancement is misleading. Hippokratia 2016, 20(3): 192-197.}, } @article {pmid27362268, year = {2016}, author = {Gertz, EM and Chowdhury, SA and Lee, WJ and Wangsa, D and Heselmeyer-Haddad, K and Ried, T and Schwartz, R and Schäffer, AA}, title = {FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe.}, journal = {PloS one}, volume = {11}, number = {6}, pages = {e0158569}, pmid = {27362268}, issn = {1932-6203}, support = {R01 CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *Databases, Genetic ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Ploidies ; Uterine Cervical Neoplasms/*genetics/pathology ; }, abstract = {Advances in fluorescence in situ hybridization (FISH) make it feasible to detect multiple copy-number changes in hundreds of cells of solid tumors. Studies using FISH, sequencing, and other technologies have revealed substantial intra-tumor heterogeneity. The evolution of subclones in tumors may be modeled by phylogenies. Tumors often harbor aneuploid or polyploid cell populations. Using a FISH probe to estimate changes in ploidy can guide the creation of trees that model changes in ploidy and individual gene copy-number variations. We present FISHtrees 3.0, which implements a ploidy-based tree building method based on mixed integer linear programming (MILP). The ploidy-based modeling in FISHtrees includes a new formulation of the problem of merging trees for changes of a single gene into trees modeling changes in multiple genes and the ploidy. When multiple samples are collected from each patient, varying over time or tumor regions, it is useful to evaluate similarities in tumor progression among the samples. Therefore, we further implemented in FISHtrees 3.0 a new method to build consensus graphs for multiple samples. We validate FISHtrees 3.0 on a simulated data and on FISH data from paired cases of cervical primary and metastatic tumors and on paired breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Tests on simulated data show improved accuracy of the ploidy-based approach relative to prior ploidyless methods. Tests on real data further demonstrate novel insights these methods offer into tumor progression processes. Trees for DCIS samples are significantly less complex than trees for paired IDC samples. Consensus graphs show substantial divergence among most paired samples from both sets. Low consensus between DCIS and IDC trees may help explain the difficulty in finding biomarkers that predict which DCIS cases are at most risk to progress to IDC. The FISHtrees software is available at ftp://ftp.ncbi.nih.gov/pub/FISHtrees.}, } @article {pmid27358153, year = {2016}, author = {Alessio, C and Scali, E and Manti, F and Amoruso, GF and Marchese, S and Riga, B and Bottoni, U and Tamburrini, O}, title = {An unusual case of mammary Paget’s disease in a woman with psoriasis.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {30}, number = {2}, pages = {589-592}, pmid = {27358153}, issn = {0393-974X}, mesh = {Breast Neoplasms/*etiology ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*etiology ; Psoriasis/*complications ; }, abstract = {Mammary Paget’s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60-year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget’s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget’s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget’s disease and psoriasis has never been described.}, } @article {pmid27357177, year = {2016}, author = {De La Cruz, L and Blankenship, SA and Chatterjee, A and Geha, R and Nocera, N and Czerniecki, BJ and Tchou, J and Fisher, CS}, title = {Outcomes After Oncoplastic Breast-Conserving Surgery in Breast Cancer Patients: A Systematic Literature Review.}, journal = {Annals of surgical oncology}, volume = {23}, number = {10}, pages = {3247-3258}, doi = {10.1245/s10434-016-5313-1}, pmid = {27357177}, issn = {1534-4681}, mesh = {Breast Neoplasms/pathology/*surgery ; Disease-Free Survival ; Esthetics ; Female ; Humans ; *Mammaplasty/adverse effects ; Mastectomy, Segmental/adverse effects/*methods ; Neoplasm Metastasis ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplasm, Residual ; Reoperation ; Survival Rate ; }, abstract = {BACKGROUND: Surgeons have increasingly performed breast-conserving surgery (BCS) utilizing oncoplastic techniques in place of standard lumpectomy for early-stage breast cancer. We assess oncologic outcomes after oncoplastic BCS for T1-T2 breast cancer.

METHODS: A systematic literature review identified peer-reviewed articles in PubMed evaluating BCS with oncoplastic reconstruction. Selected studies reported on positive margin rate (PMR), re-excision rate (RR), conversion to mastectomy rate (CMR), overall survival (OS), disease-free survival (DFS), local recurrence (LR), distant recurrence (DR), complication rate, and/or cosmetic outcomes.

RESULTS: The search yielded 474 articles; 55 met the inclusion criteria and collectively evaluated 6011 patients with a mean age 54.6 years over a mean follow-up 50.5 months. T1 (43.8 %) and T2 (39.3 %) invasive ductal carcinoma were the most common tumor histopathologies. PMR, RR, and CMR were 10.8, 6.0, and 6.2 %, respectively, while OS, DFS, LR and DR were 95.0, 90.0, 3.2, and 8.7 %, respectively. Margin widths were heterogeneously defined in studies that included margin assessment. The PMR was not significantly different when positive margins were defined as tumor <10, <5, < 2, and <1 mm from ink margin, or tumor on ink (p = 0.162). Eleven studies reported specific margins for 1455 patients, of whom 143 (9.8 %) had positive margins, including 113 (7.8 %) with tumor on ink.

CONCLUSIONS: This study is the largest comprehensive literature review to date on oncoplastic BCS. Our systematic review reveals high rates of OS and DFS with low LR, DR, PMR, RR, CMR and complication rates, thereby confirming the oncologic safety of this procedure in patients with T1-T2 invasive breast cancer.}, } @article {pmid27355204, year = {2016}, author = {Winn, JS and Baker, MG and Fanous, IS and Slack-Davis, JK and Atkins, KA and Dillon, PM}, title = {Lobular Breast Cancer and Abdominal Metastases: A Retrospective Review and Impact on Survival.}, journal = {Oncology}, volume = {91}, number = {3}, pages = {135-142}, doi = {10.1159/000447264}, pmid = {27355204}, issn = {1423-0232}, mesh = {Abdominal Neoplasms/*secondary/therapy ; Age Factors ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Breast Neoplasms, Male/pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Carcinoma, Lobular/*secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Male ; Mastectomy, Segmental ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Neoplasm Staging ; Neoplasm, Residual ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The predominant breast cancer subtypes, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), have similar recurrence and survival rates but differing patterns of metastatic recurrence.

METHODS: A retrospective review of breast cancers treated at an academic medical center from 1999 to 2012 was performed. Demographic, pathologic, treatment, and follow-up data were collected for 179 ILC and 358 IDC patients (1:2 stage-matched). The median follow-up was 4.7 years.

RESULTS: The baseline characteristics were similar in the two groups. ILC was more likely to be hormone-receptor-positive/HER2-negative and mammographically occult. The number of surgical resections, breast conservation rate, systemic treatment, and taxane use was similar between the groups. The overall recurrence rate was the same. ILC recurred more often in the abdominal cavity (24.3% in ILC vs. 4.1% in IDC, p = 0.001). The disease-free survival and overall survival were equal. On multivariate analysis, age, stage of disease, hormone receptor status, and systemic therapy were associated with survival, but histology was not.

CONCLUSIONS: Compared to ductal breast cancers, lobular breast cancers recur more often in the abdominal cavity. Both ILC and IDC have comparable surgical and medical treatment outcomes and survival. Our data suggest that enhanced surveillance and imaging might be useful in ILC.}, } @article {pmid27353975, year = {2016}, author = {Timpano, H and Chan Ho Tong, L and Gautier, V and Lalucque, H and Silar, P}, title = {The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.}, journal = {Fungal genetics and biology : FG & B}, volume = {94}, number = {}, pages = {1-10}, doi = {10.1016/j.fgb.2016.06.006}, pmid = {27353975}, issn = {1096-0937}, mesh = {Fungal Proteins/genetics ; *Gene Expression Regulation, Fungal ; *Gene Regulatory Networks ; Genetic Complementation Test ; Mutation ; Mycelium/*genetics/growth & development ; Phosphorylation ; Podospora/*genetics/growth & development ; }, abstract = {In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes.}, } @article {pmid27352956, year = {2017}, author = {Jafarpour-Sadegh, F and Montazeri, V and Adili, A and Esfehani, A and Rashidi, MR and Pirouzpanah, S}, title = {Consumption of Fresh Yellow Onion Ameliorates Hyperglycemia and Insulin Resistance in Breast Cancer Patients During Doxorubicin-Based Chemotherapy: A Randomized Controlled Clinical Trial.}, journal = {Integrative cancer therapies}, volume = {16}, number = {3}, pages = {276-289}, pmid = {27352956}, issn = {1552-695X}, mesh = {Adult ; Blood Glucose/drug effects ; Body Mass Index ; Breast Neoplasms/*drug therapy ; Diet/methods ; Doxorubicin/*adverse effects/*therapeutic use ; Female ; Homeostasis/drug effects ; Humans ; Hyperglycemia/*drug therapy ; Insulin/metabolism ; Insulin Resistance/*physiology ; Middle Aged ; Onions/*chemistry ; Plant Preparations/*pharmacology ; }, abstract = {PURPOSE: Doxorubicin has been found to be associated with insulin resistance in animal models. Onion, a so-called functional food, is noted to affect the insulin signaling pathway of diabetes in vitro. To our knowledge, this is the first study to investigate the effects of consuming fresh yellow onions on insulin-related indices compared with a low-onion-containing diet among breast cancer (BC) patients treated with doxorubicin.

METHODS: This parallel-design, randomized, triple-blind, controlled clinical trial was conducted on 56 eligible BC patients (aged 30-63 years), diagnosed with invasive ductal carcinoma. Following their second cycle of chemotherapy, subjects were assigned in a stratified-random allocation to receive body mass index-dependent 100 to 160 g/d of onion as high onion group (HO; n = 28) or 30 to 40 g/d small onions in low onion group (LO; n = 28) for 8 weeks intervention. Participants, care givers, and those who assessed laboratory analyses were blinded to the assignments (IRCT Registry No.: IRCT2012103111335N1).

RESULTS: The compliance level of participants in the analysis was as high as 87.85%. A total of 23 available cases was analyzed in each group. The daily use of HO resulted in a significant decrease in serum fasting blood glucose and insulin levels in comparison with LO, over the period of study (P < .001). Posttreatment with HO showed a significant decrease in homeostasis model of assessment-insulin resistance relative to changes in the LO group (P < .05). A comparison of the changes that occurred throughout pre- and postdose treatments indicated improved quantitative insulin sensitivity check index (P < .05) and controls on C-peptide in the HO group (P < .05).

CONCLUSIONS: The present study demonstrated the effectiveness of onion to ameliorate hyperglycemia and insulin resistance in BC during doxorubicin-based chemotherapy.}, } @article {pmid27351926, year = {2016}, author = {Kanat-Maymon, Y and Sarid, O and Mor, Y and Mirsky, J and Slonim-Nevo, V}, title = {Gaps Between Immigrant Spouses in Host Country Language Proficiency: Longitudinal Effects on Marital Satisfaction.}, journal = {The Journal of psychology}, volume = {150}, number = {6}, pages = {793-808}, doi = {10.1080/00223980.2016.1196159}, pmid = {27351926}, issn = {1940-1019}, mesh = {Adult ; Emigrants and Immigrants/*psychology ; Female ; Germany ; Humans ; Israel ; Longitudinal Studies ; Male ; Marriage/*psychology ; Middle Aged ; *Multilingualism ; *Personal Satisfaction ; Spouses/*psychology ; USSR ; }, abstract = {Research on immigration underscores the importance of language acculturation in successful adjustment to life in a new country. However, the profound impact of different levels of language proficiency between immigrant spouses on their married life is an understudied topic. The current study explores whether differences between immigrant spouses in host language proficiency predict marital satisfaction in their first four years in the host country. Using a three-wave longitudinal study, with intervals of one to two years, we collected data from 316 married couples who immigrated from the Former Soviet Union to Germany and Israel. Language proficiency and marital satisfaction were measured via self-report questionnaires. We conducted an Actor-Partner Interdependence Model analysis to control for dyadic and time data dependencies. The results indicate that differences between spouses in their host language proficiency predict marital dissatisfaction, and that this effect is exacerbated over time. These associations held across gender and host country. The findings are discussed in light of the gap-distress model.}, } @article {pmid27351316, year = {2017}, author = {Solak, N and Reifen Tagar, M and Cohen-Chen, S and Saguy, T and Halperin, E}, title = {Disappointment expression evokes collective guilt and collective action in intergroup conflict: the moderating role of legitimacy perceptions.}, journal = {Cognition & emotion}, volume = {31}, number = {6}, pages = {1112-1126}, doi = {10.1080/02699931.2016.1197098}, pmid = {27351316}, issn = {1464-0600}, mesh = {Adolescent ; Adult ; Aged ; *Conflict, Psychological ; *Emotions ; Female ; *Group Processes ; *Guilt ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {Research on intergroup emotions has largely focused on the experience of emotions and surprisingly little attention has been given to the expression of emotions. Drawing on the social-functional approach to emotions, we argue that in the context of intergroup conflicts, outgroup members' expression of disappointment with one's ingroup induces the complementary emotion of collective guilt and correspondingly a collective action protesting ingroup actions against the outgroup. In Study 1 conducted immediately after the 2014 Gaza war, Jewish-Israeli participants received information about outgroup's (Palestinians) expression of emotions (disappointment, fear, or none). As predicted, outgroup's expression of disappointment increased collective guilt and willingness to participate in collective action, but only among those who saw the intergroup situation as illegitimate. Moreover, collective guilt mediated the relationship between disappointment expression and collective action, moderated, again, by legitimacy perception. In Study 2, we replicated these results in the context of racial tension between Black and White Americans in the US. We discuss the theoretical and applied implications of the findings.}, } @article {pmid27345691, year = {2016}, author = {Giroud, M and Karbiener, M and Pisani, DF and Ghandour, RA and Beranger, GE and Niemi, T and Taittonen, M and Nuutila, P and Virtanen, KA and Langin, D and Scheideler, M and Amri, EZ}, title = {Let-7i-5p represses brite adipocyte function in mice and humans.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {28613}, pmid = {27345691}, issn = {2045-2322}, mesh = {Adipocytes, Beige/*metabolism/physiology ; Adipocytes, Brown/metabolism/physiology ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism/physiology ; Adipose Tissue, White/metabolism/physiology ; Animals ; Down-Regulation/physiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*metabolism ; Obesity/metabolism ; Oxygen Consumption/physiology ; Receptors, Adrenergic, beta-3/metabolism ; Thermogenesis/physiology ; Uncoupling Protein 1/metabolism ; }, abstract = {In response to cold or β3-adrenoreceptor stimulation brown adipose tissue (BAT) promotes non-shivering thermogenesis, leading to energy dissipation. BAT has long been thought to be absent or scarce in adult humans. The recent discovery of thermogenic brite/beige adipocytes has opened the way to development of novel innovative strategies to combat overweight/obesity and associated diseases. Thus it is of great interest to identify regulatory factors that govern the brite adipogenic program. Here, we carried out global microRNA (miRNA) expression profiling on human adipocytes to identify miRNAs that are regulated upon the conversion from white to brite adipocytes. Among the miRNAs that were differentially expressed, we found that Let-7i-5p was down regulated in brite adipocytes. A detailed analysis of the Let-7i-5p levels showed an inverse expression of UCP1 in murine and human brite adipocytes both in vivo and in vitro. Functional studies with Let-7i-5p mimic in human brite adipocytes in vitro revealed a decrease in the expression of UCP1 and in the oxygen consumption rate. Moreover, the Let-7i-5p mimic when injected into murine sub-cutaneous white adipose tissue inhibited partially β3-adrenergic activation of the browning process. These results suggest that the miRNAs Let-7i-5p participates in the recruitment and the function of brite adipocytes.}, } @article {pmid27333920, year = {2016}, author = {Onodera, Y and Takagi, K and Miki, Y and Takayama, K and Shibahara, Y and Watanabe, M and Ishida, T and Inoue, S and Sasano, H and Suzuki, T}, title = {TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.}, journal = {Cancer medicine}, volume = {5}, number = {8}, pages = {1973-1982}, pmid = {27333920}, issn = {2045-7634}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*mortality/pathology ; Carrier Proteins/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gonadal Steroid Hormones/metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/metabolism ; }, abstract = {Transforming acidic coiled-coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF-7 and MDA-MB-453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5-Bromo-2'-deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki-67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer-specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease-free and breast cancer-specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF-7 and MDA-MB-453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases.}, } @article {pmid27330877, year = {2016}, author = {Garcia, R and Sallabanda, K and Santa-Olalla, I and Lopez Guerra, JL and Avilés, L and Sallabanda, M and Rivin, E and Samblás, J}, title = {Robotic Radiosurgery for the Treatment of Intramedullary Spinal Cord Metastases: A Case Report and Literature Review.}, journal = {Cureus}, volume = {8}, number = {5}, pages = {e609}, pmid = {27330877}, issn = {2168-8184}, abstract = {Modern technologies allow the delivery of high radiation doses to intramedullary spinal cord metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. This study evaluates the acute and late toxicity outcomes in a patient treated with robotic radiosurgery for an intramedullary spinal cord metastasis. A 50-year-old woman diagnosed in May 2006 with invasive ductal carcinoma of the right breast T2N3M1 (two liver metastases) received chemotherapy with a complete response. Subsequently, she underwent adjuvant whole-breast radiotherapy, along with tamoxifen. After several distant relapses, treated mainly with systemic therapy, the patient developed an intramedullary lesion at the C3-C4 level and was referred to our CyberKnife unit for assessment. A total dose of 14 Gy prescribed to the 74% isodose line was administered to the intramedullary lesion in one fraction. One hundred and two treatment beams were used covering 95.63% of the target volume. The mean dose was 15.93 Gy and the maximum dose, 18.92 Gy. Maximum dose to the spinal cord was 13.96 Gy, V12 ~ 0.13 cc and V8 ~ 0.43 cc. Three months after treatment, magnetic resonance imaging showed a reduction in size and enhancement of the intramedullary lesion with no associated toxicity. During this period, the patient showed a good performance status without neurological deficits. Currently, with a follow-up of 37 months, the patient has the ability to perform activities of daily life. Intramedullary spinal cord metastases is a rare and aggressive disease, often treatment-refractory. Our case demonstrates that radiation therapy delivery with robotic radiosurgery allows the achievement of a high local control without adding toxicity.}, } @article {pmid27323669, year = {2016}, author = {Gautheron, J and Vucur, M and Schneider, AT and Severi, I and Roderburg, C and Roy, S and Bartneck, M and Schrammen, P and Diaz, MB and Ehling, J and Gremse, F and Heymann, F and Koppe, C and Lammers, T and Kiessling, F and Van Best, N and Pabst, O and Courtois, G and Linkermann, A and Krautwald, S and Neumann, UP and Tacke, F and Trautwein, C and Green, DR and Longerich, T and Frey, N and Luedde, M and Bluher, M and Herzig, S and Heikenwalder, M and Luedde, T}, title = {The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11869}, pmid = {27323669}, issn = {2041-1723}, support = {208237/ERC_/European Research Council/International ; }, mesh = {Adipocytes/enzymology/pathology ; Adipose Tissue, White/*enzymology/pathology ; Animals ; Apoptosis/genetics ; Body Mass Index ; Caspase 8/genetics/metabolism ; Choline/metabolism ; Choline Deficiency/enzymology/etiology/*genetics/pathology ; Diet, High-Fat ; Gene Expression Regulation ; Glucose Intolerance/enzymology/etiology/*genetics/pathology ; Homeostasis ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intra-Abdominal Fat/*enzymology/pathology ; Male ; Mice ; Necrosis/*enzymology/genetics/pathology ; Obesity/enzymology/etiology/*genetics/pathology ; Receptor-Interacting Protein Serine-Threonine Kinases/*genetics/metabolism ; }, abstract = {Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients.}, } @article {pmid27306813, year = {2016}, author = {Terasawa, R and Iwamoto, M and Tanaka, S and Kimura, K and Takahashi, Y and Fujioka, H and Sato, N and Kawaguchi, K and Ikari, A and Maezawa, S and Tominaga, T and Matsuda, J and Umezaki, N and Uchiyama, K}, title = {[A Case of Squamous Cell Carcinoma of the Breast].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {6}, pages = {749-752}, pmid = {27306813}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Squamous Cell/*diagnosis/therapy ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Fatal Outcome ; Female ; Humans ; Recurrence ; Thoracic Wall/*pathology ; }, abstract = {Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.}, } @article {pmid27302492, year = {2016}, author = {Jiang, R and Ma, Z and Dong, H and Sun, S and Zeng, X and Li, X}, title = {Diffusion tensor imaging of breast lesions: evaluation of apparent diffusion coefficient and fractional anisotropy and tissue cellularity.}, journal = {The British journal of radiology}, volume = {89}, number = {1064}, pages = {20160076}, pmid = {27302492}, issn = {1748-880X}, mesh = {Adult ; Aged ; Anisotropy ; Breast Diseases/*diagnostic imaging/*pathology ; Breast Neoplasms/*diagnostic imaging/*pathology ; Cell Count ; *Diffusion Tensor Imaging ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: To investigate the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) measured by diffusion tensor imaging (DTI), tissue cellularity and their relationship in breast malignant/benign lesions.

METHODS: 88 patients with 88 breast lesions who underwent DTI and dynamic contrast-enhanced MR scanning between November 2013 and December 2014 were retrospectively analyzed. The diagnosis was confirmed pathologically. ADC and FA values as well as histopathological cellularity of different pathological types of lesions were analyzed and compared statistically. The Pearson's correlation between cellularity and ADC and FA was calculated.

RESULTS: There were 59 cases of breast cancer and 29 cases of benign lesions included in the study. ADC values of breast cancers were statistically lower than that of benign lesions (p < 0.001). FA and cellularity were higher in cancers than in benign lesions with statistical significance (p < 0.05 and p < 0.001, respectively). The mean FA values in the patients with invasive ductal carcinoma (IDC) were higher than that in the patients with ductal carcinoma in situ (DCIS) without statistical difference (p > 0.05). The ADC and the cellularity in the IDC of grade III were statistically lower (p < 0.05) and higher (p < 0.05) than that in the DCIS and IDC of grade I-II, respectively. ADC was negatively correlated to cellularity (r = -0.8319, p < 0.001) and FA was positively correlated to cellularity (r = 0.4231, p < 0.001).

CONCLUSION: ADC and FA values were statistically different between benign and malignant breast lesions and were significantly correlated to tissue cellularity. ADC and FA may help to discriminate malignant from benign breast lesions and to predict cellularity. ADC is helpful in the prediction of the grade of breast cancer.

ADVANCES IN KNOWLEDGE: ADC and FA values were statistically different between benign and malignant breast lesions and were significantly correlated to tissue cellularity.}, } @article {pmid27293986, year = {2016}, author = {Jablonska, K and Grzegrzolka, J and Podhorska-Okolow, M and Stasiolek, M and Pula, B and Olbromski, M and Gomulkiewicz, A and Piotrowska, A and Rys, J and Ambicka, A and Ong, SH and Zabel, M and Dziegiel, P}, title = {Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients.}, journal = {American journal of cancer research}, volume = {6}, number = {5}, pages = {878-893}, pmid = {27293986}, issn = {2156-6976}, abstract = {Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS but not with OS.}, } @article {pmid27286855, year = {2016}, author = {Moccia, M and Pellecchia, MT and Spina, E and Barone, P and Vitale, C}, title = {Bilirubin and Uric Acid: Two Different Anti-oxidants in Parkinson's Disease.}, journal = {Cell biochemistry and biophysics}, volume = {74}, number = {2}, pages = {91-92}, doi = {10.1007/s12013-015-0717-2}, pmid = {27286855}, issn = {1559-0283}, mesh = {Antioxidants/*metabolism ; Bilirubin/*metabolism ; Disease Progression ; Humans ; Parkinson Disease/*metabolism/pathology ; Uric Acid/*metabolism ; }, } @article {pmid27286830, year = {2016}, author = {Sopik, V and Narod, SA}, title = {Common genetic susceptibility to DCIS and invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {18}, number = {1}, pages = {60}, pmid = {27286830}, issn = {1465-542X}, mesh = {Breast Neoplasms ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; *Carcinoma, Intraductal, Noninfiltrating ; *Genetic Predisposition to Disease ; Humans ; Neoplasm Invasiveness ; }, } @article {pmid27284958, year = {2016}, author = {Ross, JS and Gay, LM and Wang, K and Ali, SM and Chumsri, S and Elvin, JA and Bose, R and Vergilio, JA and Suh, J and Yelensky, R and Lipson, D and Chmielecki, J and Waintraub, S and Leyland-Jones, B and Miller, VA and Stephens, PJ}, title = {Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti-HER2 targeted therapies.}, journal = {Cancer}, volume = {122}, number = {17}, pages = {2654-2662}, doi = {10.1002/cncr.30102}, pmid = {27284958}, issn = {1097-0142}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/secondary ; Carcinoma, Lobular/drug therapy/genetics/secondary ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic/drug effects ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; *Molecular Targeted Therapy ; Mutation/*genetics ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/drug therapy/*genetics/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/antagonists & inhibitors/*genetics ; }, abstract = {BACKGROUND: Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified.

METHODS: DNA was extracted from 40 µm of formalin-fixed paraffin-embedded (FFPE) sections. Comprehensive genomic profiling (CGP) was used to evaluate up to 315 genes (592× mean coverage depth). Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.

RESULTS: Of 5605 cases, 698 (12.5%) featured ERBB2 alterations, including 596 (10.6%) ERBB2 amplifications (ERBB2amp) and 138 (2.4%) ERBB2mut; 38 cases (0.7%) had co-occurring ERBB2amp and ERBB2mut. ERBB2mut predominantly affected the kinase (124 cases; 90%) or extracellular (15 cases; 11%) domains. Both primary BC (52 cases; 38%) and metastatic site biopsies (86 cases; 62%) were found to harbor ERBB2mut, which were distributed across carcinoma not otherwise specified (NOS) (69 cases; 50%), invasive ductal carcinoma (IDC) (40 cases; 29%), invasive lobular carcinoma (ILC) (27 cases; 20%), and mucinous mBC (2 cases; 1%). Genes commonly coaltered with ERBB2 were tumor protein 53 (TP53) (49%); phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (42%); cadherin 1, type 1 (CDH1) (37%); MYC (17%); and cyclin D1 protein (CCND1) (16%). CDH1 mutations were enriched in ERBB2mut mBC (P<0.0006) and associated with recurrent mBC. Selected patients with ERBB2mut, without ERBB2amp, who responded to anti-HER2 targeted therapies are presented herein.

CONCLUSIONS: Within this large series, 1.8% of cases harbored ERBB2mut, which are undetectable by standard-of-care IHC or FISH tests. Metastatic BC driven by ERBB2mut respond to anti-HER2 targeted therapies, and expanding clinical trials designed to detect ERBB2mut by CGP and optimize targeted treatments are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2654-2662. © 2016 American Cancer Society.}, } @article {pmid27279334, year = {2016}, author = {Shen, S and Wang, Y and Wang, C and Wu, YN and Xing, Y}, title = {SURVIV for survival analysis of mRNA isoform variation.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11548}, pmid = {27279334}, issn = {2041-1723}, support = {R01 GM088342/GM/NIGMS NIH HHS/United States ; R01 GM105431/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Breast Neoplasms/*etiology/mortality ; Carcinoma, Ductal, Breast/*etiology/mortality ; Humans ; Models, Statistical ; *RNA Isoforms ; *Survival Analysis ; }, abstract = {The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects.}, } @article {pmid27275301, year = {2015}, author = {Youssef, SS and Mohammad, MM and Ezz-El-Arab, LR}, title = {Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers.}, journal = {Open access Macedonian journal of medical sciences}, volume = {3}, number = {4}, pages = {640-644}, pmid = {27275301}, issn = {1857-9655}, abstract = {AIM: To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio.

METHODS: Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded.

RESULTS: BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio.

CONCLUSION: IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value.}, } @article {pmid27271765, year = {2016}, author = {Di Meglio, A and Freedman, RA and Lin, NU and Barry, WT and Metzger-Filho, O and Keating, NL and King, TA and Sertoli, MR and Boccardo, F and Winer, EP and Vaz-Luis, I}, title = {Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis.}, journal = {Breast cancer research and treatment}, volume = {157}, number = {3}, pages = {587-596}, doi = {10.1007/s10549-016-3845-5}, pmid = {27271765}, issn = {1573-7217}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Female ; Humans ; Incidence ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; SEER Program ; Survival Analysis ; United States/epidemiology ; Young Adult ; }, abstract = {Few contemporary data are available that compare incidence and survival of metastatic breast cancer between ductal and lobular carcinomas. Using the Surveillance, Epidemiology, and End Results-9 registries, we identified 10,639 patients with de novo metastatic breast cancer diagnosed from 1990 to 2011. Annual age-adjusted incidence rates and annual percent changes (APCs) were analyzed. Multivariable Cox regression models were used to investigate the impact of year of diagnosis and histology on overall survival. 9250 (86.9 %) patients had ductal and 1389 (13.1 %) had lobular carcinomas. Metastatic breast cancer incidence increased slightly over time for ductal (APC = +1.7, 95 % confidence interval (CI) = +1.0 to +2.4) and lobular carcinomas (APC = +3.0, 95 % CI = +1.8 to +4.3). Median overall survival was 22 months among the whole cohort. More recent year of diagnosis was associated with better overall survival only for patients with ductal carcinomas (interaction p value = 0.006), with an adjusted hazard ratio of death for every five-year increment in the date of diagnosis of 0.93 (95 % CI = 0.91-0.95) among ductal carcinomas, compared with 1.05 (95 % CI = 0.95-1.10) among lobular carcinomas. Overall survival was longer for lobular versus ductal carcinomas (28 versus 21 months, respectively; adjusted hazard ratio of death = 0.93, 95 % CI = 0.87-0.99), but the magnitude of this effect was attenuated among the cohort restricted to hormone receptor-positive tumors. In this population-based analysis, incidence rates of metastatic breast cancer at presentation increased slightly over time for both histologies, and particularly for lobular tumors. A modest improvement in metastatic breast cancer median overall survival was observed, but was apparently limited to ductal carcinomas.}, } @article {pmid27270946, year = {2016}, author = {Dölen, UC and Sachanandani, NS and Tung, TH}, title = {Internal mammary artery perforator propeller flap for contralateral mastectomy defect: A case report.}, journal = {Microsurgery}, volume = {36}, number = {6}, pages = {507-510}, doi = {10.1002/micr.30080}, pmid = {27270946}, issn = {1098-2752}, mesh = {Adult ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; Mammaplasty/*methods ; Mammary Arteries/*surgery ; *Mastectomy ; Perforator Flap/*blood supply ; }, abstract = {The internal mammary artery perforator (IMAP) flap can be used as either loco-regional or free flap, and provides thin flexible coverage for defects of the chest wall and cervical regions. In this report, we present a bilateral mastectomy case in which the left mastectomy defect was closed with an IMAP propeller flap harvested from the right breast. Our patient with a history of left breast conservation therapy was diagnosed invasive ductal carcinoma in her left breast 14 years later. On physical examination, the patient's left breast displayed the stigmata of radiotherapy including dark discoloration and firmness to palpation, compared to contralateral pendulous breast. After bilateral mastectomy, an IMAP flap with a size of 26 cm × 11 cm was harvested from right chest and was transposed 180 degrees clockwise in a propeller fashion to the left mastectomy defect without any tension. The flap survived without any complication and the patient was free of recurrence or metastases during the follow-up of 18 months. The patient was satisfied with the outcome. IMAP propeller flap could be harvested safely to the anterior axillary fold in the subcutaneous fat plane. It may provide a large skin paddle especially in large breasted women. © 2016 Wiley Periodicals, Inc. Microsurgery 36:507-510, 2016.}, } @article {pmid27268636, year = {2016}, author = {Amirifard, N and Sadeghi, E}, title = {Breast Cancer in Men: a Report from the Department of Radiation Oncology in Kermanshah Province, Iran.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {5}, pages = {2593-2596}, pmid = {27268636}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/therapy ; Carcinoma, Lobular/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Iran ; Male ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms/*drug therapy/pathology ; Prognosis ; Radiation Oncology ; *Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. In this study, we retrospectively evaluated the clinicopathological features, treatment options and overall survival in Kurdish MBC cases.

MATERIALS AND METHODS: Seventeen MBC were referred to Department of Radiation Oncology in Imam Reza Hospital, Kermanshah, Iran, between 2010 and 2016. Immunohistochemical analysis was performed for ER, PR and Her2 biomarkers and FISH for those with Her2 2+. Median follow-up period was 30 months (2-65 months). We excluded from the study patients who did not have follow-up after initial diagnosis. Treatment methods were chemotherapy, radiotherapy, hormonal therapy, target therapy and palliative care. Survival was estimated by the Kaplan Meier method (Prism 5).

RESULTS: The mean age at diagnosis was 49.2 ± 17 years (range, 24-85 years). Grade II was the most grade in MBC (65%). Fourteen patients (82%) had invasive ductal carcinoma, one (6%) had ductal carcinoma in situ and 2 (12%) had invasive papillary. ER, PR and Her2 were significantly positive in 14/17, 8/17 and 2/17 cases, respectively. The treatment included modified radical mastectomy for most patients. Chemotherapy with TAC and CEF regimens was delivered to 15/17 cases. Tamoxifen therapy was delivered to 14/17 cases. Three stage IV patients received Avestin and two with Her2 3+ were given Trastuzumab (Herceptin). Patients received adjuvant radiotherapy following surgery and chemotherapy. The site of metastasis was the bone in 2 cases, lung in 1 case and liver in 1 case. Zoledronic acid (Zometa) was prescribed for patients with bone metastasis. Five-year overall survival rate was 64%.

CONCLUSIONS: MBC is rare. Thus, we need larger studies are in collaboration with several research centers in the field of breast cancer. ER positive, grade II of invasive ductal carcinoma, stage II and right side happened more with MBC. Overall survival is similar to other studies.}, } @article {pmid27267193, year = {2016}, author = {Desmond, BL and Blattner, CM and Young Iii, J}, title = {Generalized morphea as the first sign of breast carcinoma: a case report.}, journal = {Dermatology online journal}, volume = {22}, number = {2}, pages = {}, pmid = {27267193}, issn = {1087-2108}, mesh = {Breast Neoplasms/*complications/diagnosis ; Carcinoma, Ductal, Breast/*complications/diagnosis ; Female ; Humans ; Middle Aged ; Paraneoplastic Syndromes/*complications/pathology ; Scleroderma, Localized/*complications/pathology ; }, abstract = {Generalized morphea is a rare idiopathic form of scleroderma that literally means "hard skin." Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc).}, } @article {pmid27266558, year = {2016}, author = {Freed, M and Storey, P and Lewin, AA and Babb, J and Moccaldi, M and Moy, L and Kim, SG}, title = {Evaluation of Breast Lipid Composition in Patients with Benign Tissue and Cancer by Using Multiple Gradient-Echo MR Imaging.}, journal = {Radiology}, volume = {281}, number = {1}, pages = {43-53}, pmid = {27266558}, issn = {1527-1315}, support = {R01 CA160620/CA/NCI NIH HHS/United States ; }, mesh = {Adipose Tissue/*chemistry ; Adult ; Aged ; Breast Diseases/*diagnostic imaging/*metabolism ; Breast Neoplasms/diagnostic imaging/metabolism ; Fatty Acids/*metabolism ; Feasibility Studies ; Female ; Humans ; Image Interpretation, Computer-Assisted ; *Imaging, Three-Dimensional ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 ± 0.06 vs 0.46 ± 0.10; P < .05) and SFA was higher (0.31 ± 0.07 vs 0.19 ± 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 ± 0.06 vs 0.27 ± 0.05; P < .01) and lower SFA (0.19 ± 0.11 vs 0.30 ± 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (©) RSNA, 2016 Online supplemental material is available for this article.}, } @article {pmid27265347, year = {2016}, author = {Uesaka, K and Boku, N and Fukutomi, A and Okamura, Y and Konishi, M and Matsumoto, I and Kaneoka, Y and Shimizu, Y and Nakamori, S and Sakamoto, H and Morinaga, S and Kainuma, O and Imai, K and Sata, N and Hishinuma, S and Ojima, H and Yamaguchi, R and Hirano, S and Sudo, T and Ohashi, Y and , }, title = {Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01).}, journal = {Lancet (London, England)}, volume = {388}, number = {10041}, pages = {248-257}, doi = {10.1016/S0140-6736(16)30583-9}, pmid = {27265347}, issn = {1474-547X}, mesh = {Aged ; Antimetabolites, Antineoplastic/*administration & dosage ; Carcinoma, Ductal/mortality/pathology/*therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/*analogs & derivatives ; Drug Combinations ; Female ; Humans ; Injections, Intravenous ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Oxonic Acid/*administration & dosage ; *Pancreatectomy ; Pancreatic Neoplasms/mortality/*therapy ; Proportional Hazards Models ; Tegafur/*administration & dosage ; Gemcitabine ; }, abstract = {BACKGROUND: Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival.

METHODS: We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655).

FINDINGS: 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority<0.0001, p<0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group.

INTERPRETATION: Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients.

FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.}, } @article {pmid27258056, year = {2016}, author = {Ahuja, S and Makkar, P and Gupta, S and Vigoda, I}, title = {Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.}, journal = {The Journal of community and supportive oncology}, volume = {14}, number = {5}, pages = {229-231}, doi = {10.12788/jcso.0186}, pmid = {27258056}, issn = {2330-7749}, abstract = {Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.}, } @article {pmid27255575, year = {2017}, author = {Bond, SE and Boutlis, CS and Jansen, SG and Miyakis, S}, title = {Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery.}, journal = {ANZ journal of surgery}, volume = {87}, number = {11}, pages = {E199-E203}, doi = {10.1111/ans.13642}, pmid = {27255575}, issn = {1445-2197}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Antibiotic Prophylaxis/standards ; Arthroplasty/*adverse effects ; Australia/epidemiology ; Bacteremia/drug therapy/prevention & control ; Bacteriuria/drug therapy/prevention & control ; Catheters, Indwelling/adverse effects/microbiology/*standards ; Device Removal/adverse effects/standards ; Female ; Gentamicins/administration & dosage/*therapeutic use ; Humans ; Male ; Middle Aged ; New South Wales/epidemiology ; Orthopedic Procedures/*adverse effects ; Perioperative Care/*standards ; Practice Patterns, Physicians'/standards ; Retrospective Studies ; Surgical Wound Infection/prevention & control ; Urinary Catheters/*microbiology ; }, abstract = {BACKGROUND: Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted.

METHODS: The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics.

RESULTS: Data from 137 operations pre-intervention (6 months) were compared with 205 operations post-intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury.

CONCLUSION: A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change.}, } @article {pmid27248782, year = {2016}, author = {Gayakhe, V and Ardhapure, AV and Kapdi, AR and Sanghvi, YS and Serrano, JL and Schulzke, C}, title = {C-C Bond Formation: Synthesis of C5 Substituted Pyrimidine and C8 Substituted Purine Nucleosides Using Water Soluble Pd-imidate Complex.}, journal = {Current protocols in nucleic acid chemistry}, volume = {65}, number = {}, pages = {1.37.1-1.37.15}, doi = {10.1002/cpnc.1}, pmid = {27248782}, issn = {1934-9289}, mesh = {Chemistry Techniques, Synthetic ; Deoxyadenosines/chemical synthesis/chemistry ; Deoxyguanosine/analogs & derivatives/chemical synthesis/chemistry ; Organophosphorus Compounds/chemistry ; Palladium/chemistry ; Purine Nucleosides/*chemical synthesis/chemistry ; Pyrimidines/*chemical synthesis/chemistry ; Solubility ; Water ; }, abstract = {The synthesis of a highly efficient, water soluble [Pd(Sacc)2 (TPA)2 ] complex for C-C bond formation is described. Additionally, application of the [Pd(Sacc)2 (TPA)2 ] complex for Suzuki-Miyaura arylation of all four nucleosides (5-iodo-2'-deoxyuridine [5-IdU], 5-iodo-2'-deoxycytidine [5-IdC], 8-bromo-2'-deoxyadenosine, and 8-bromo-2'-deoxyguanosine) with various aryl/heteroaryl boronic acids in plain water under milder conditions is demonstrated. © 2016 by John Wiley & Sons, Inc.}, } @article {pmid27248207, year = {2017}, author = {Ribeiro, J and Toubekis, AG and Figueiredo, P and de Jesus, K and Toussaint, HM and Alves, F and Vilas-Boas, JP and Fernandes, RJ}, title = {Biophysical Determinants of Front-Crawl Swimming at Moderate and Severe Intensities.}, journal = {International journal of sports physiology and performance}, volume = {12}, number = {2}, pages = {241-246}, doi = {10.1123/ijspp.2015-0766}, pmid = {27248207}, issn = {1555-0273}, mesh = {Anaerobic Threshold/physiology ; Athletic Performance/physiology ; Biomechanical Phenomena ; Energy Metabolism/physiology ; Heart Rate/physiology ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption/physiology ; Respiration ; Swimming/*physiology ; Time and Motion Studies ; Upper Extremity/physiology ; Young Adult ; }, abstract = {PURPOSE: To conduct a biophysical analysis of the factors associated with front-crawl performance at moderate and severe swimming intensities, represented by anaerobic-threshold (vAnT) and maximal-oxygen-uptake (vV̇O2max) velocities.

METHODS: Ten high-level swimmers performed 2 intermittent incremental tests of 7 × 200 and 12 × 25 m (through a system of underwater push-off pads) to assess vAnT, and vV̇O2max, and power output. The 1st protocol was videotaped (3D reconstruction) for kinematic analysis to assess stroke frequency (SF), stroke length (SL), propelling efficiency (ηP), and index of coordination (IdC). V̇O2 was measured and capillary blood samples (lactate concentrations) were collected, enabling computation of metabolic power. The 2nd protocol allowed calculating mechanical power and performance efficiency from the ratio of mechanical to metabolic power.

RESULTS: Neither vAnT nor vV̇O2max was explained by SF (0.56 ± 0.06 vs 0.68 ± 0.06 Hz), SL (2.29 ± 0.21 vs 2.06 ± 0.20 m), ηP (0.38 ± 0.02 vs 0.36± 0.03), IdC (-12.14 ± 5.24 vs -9.61 ± 5.49), or metabolic-power (1063.00 ± 122.90 vs 1338.18 ± 127.40 W) variability. vV̇O2max was explained by power to overcome drag (r = .77, P ≤ .05) and ηP (r = .72, P ≤ .05), in contrast with the nonassociation between these parameters and vAnT; both velocities were well related (r = .62, P ≤ .05).

CONCLUSIONS: The biomechanical parameters, coordination, and metabolic power seemed not to be performance discriminative at either intensity. However, the increase in power to overcome drag, for the less metabolic input, should be the focus of any intervention that aims to improve performance at severe swimming intensity. This is also true for moderate intensities, as vAnT and vV˙O2max are proportional to each other.}, } @article {pmid27239051, year = {2016}, author = {Maeda, I and Tajima, S and Ariizumi, Y and Doi, M and Endo, A and Naruki, S and Hoshikawa, M and Koizumi, H and Kanemaki, Y and Ueno, T and Tsugawa, K and Takagi, M}, title = {Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?.}, journal = {Pathology international}, volume = {66}, number = {7}, pages = {369-375}, doi = {10.1111/pin.12420}, pmid = {27239051}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/*metabolism/standards ; Biopsy, Large-Core Needle ; Breast/pathology ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Reproducibility of Results ; Synaptophysin/*metabolism ; }, abstract = {The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin-positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.}, } @article {pmid27237744, year = {2016}, author = {Takei, J and Tsunoda, H and Yagata, H and Suzuki, K and Nakamura, S and Yamauchi, H}, title = {Sustained Interruption of Anterior Interfaces Between Adipose Tissues and Mammary Glands in Ultrasonography After Complete Pathological Remission After Neoadjuvant Chemotherapy for Primary Breast Cancer.}, journal = {Clinical breast cancer}, volume = {16}, number = {3}, pages = {196-201}, doi = {10.1016/j.clbc.2015.12.002}, pmid = {27237744}, issn = {1938-0666}, mesh = {Adipose Tissue/diagnostic imaging/*pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/diagnostic imaging/drug therapy/*pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Mammary Glands, Human/diagnostic imaging/*pathology ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm, Residual/diagnostic imaging/*pathology ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Interruptions of the anterior interfaces between adipose tissues and mammary glands ultrasonographically are considered highly indicative of invasive ductal carcinoma. However, ultrasonography (US) revealed sustained interruptions in some cases of complete pathological remission (pCR) after neoadjuvant chemotherapy (NAC), although invasive carcinomas remained absent. Thus, in the present study, we examined the influences of interruptions on pathology observations after pCR after NAC for primary breast cancer.

PATIENTS AND METHODS: A total of 337 patients received NAC at St Luke's International Hospital from April 2004 to September 2006, and 46 had pCRs despite residual in situ lesions (pCR ratio, 13.6%). Subsequently, the medical records of these 46 patients were retrospectively reviewed and US findings were compared with pathological findings.

RESULTS: On US, interruptions remained in 18 of 46 pCR patients. Complete fibril formations were detected in 15 cases and associated in situ lesions were detected in 4 cases.

CONCLUSION: US findings of interruptions of the anterior interface between adipose tissues and mammary glands were pathologically correlated with fibril formations and might not always indicate the presence of residual invasive cancer after NAC.}, } @article {pmid27234786, year = {2016}, author = {Kobayashi, T and Miura, K and Ishikawa, H and Soma, D and Zhang, Z and Yuza, K and Hirose, Y and Takizawa, K and Nagahashi, M and Sakata, J and Kameyama, H and Kosugi, SI and Tada, T and Hirukawa, H and Wakai, T}, title = {Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report.}, journal = {Transplantation proceedings}, volume = {48}, number = {3}, pages = {988-990}, doi = {10.1016/j.transproceed.2016.01.030}, pmid = {27234786}, issn = {1873-2623}, mesh = {Female ; Follow-Up Studies ; *Graft Survival ; Humans ; Middle Aged ; *Pancreas Transplantation ; Pancreatic Neoplasms/*surgery ; Transplantation, Heterotopic ; }, abstract = {BACKGROUND: Long-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified.

METHODS: We have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function.

RESULTS: The patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 μg/d.

CONCLUSIONS: Our patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.}, } @article {pmid27234177, year = {2016}, author = {Alkan, O and Kushnir, J and Bar, M and Kushnir, T}, title = {Quality of life of adult daughters of women with schizophrenia: Associations with psychological resource losses and gains.}, journal = {Comprehensive psychiatry}, volume = {68}, number = {}, pages = {11-17}, doi = {10.1016/j.comppsych.2016.03.002}, pmid = {27234177}, issn = {1532-8384}, mesh = {Adaptation, Psychological ; Adult ; Adult Children/*psychology ; Caregivers/psychology ; Case-Control Studies ; Child of Impaired Parents/*psychology ; Female ; Humans ; Mental Health ; Middle Aged ; Mothers/*psychology ; Quality of Life/*psychology ; Schizophrenia/diagnosis ; *Schizophrenic Psychology ; Stress, Psychological ; }, abstract = {OBJECTIVE: This study examined the relationship between perceived losses and gains of psychological resources and quality of life of adult daughters of women with schizophrenia.

METHOD: Thirty one adult daughters of mothers with schizophrenia (age range 30 to 50years) and thirty women of similar socio-demographic characteristics whose mothers were mentally healthy (the control group) participated in this study.

RESULTS: (a) Resource loss was higher and resource gains were lower among daughters of women with schizophrenia, compared to the control group; (b) despite resource gains total score of quality of life was significantly lower among daughters of mothers with schizophrenia compared to the controls; (c) daughters of mothers with schizophrenia had lower levels of family functioning, a higher level of negative emotions and a lower level of positive emotions; (d) resource gains moderated the negative relationship between resource loss and quality of life; (e) the most significant predictor of quality of life was the group (i.e. daughters of women with schizophrenia compared with controls); (f) quality of life was more strongly associated with resource loss than with resource gain.

DISCUSSION: The findings of this research underscore the importance of raising awareness of caregivers and healthcare authorities to the needs of the unique population of daughters of women diagnosed with schizophrenia for support and even treatment.}, } @article {pmid27230095, year = {2016}, author = {Shibusawa, M and Nakayama, R and Okanami, Y and Kashikura, Y and Imai, N and Nakamura, T and Kimura, H and Yamashita, M and Hanamura, N and Ogawa, T}, title = {The usefulness of a computer-aided diagnosis scheme for improving the performance of clinicians to diagnose non-mass lesions on breast ultrasonographic images.}, journal = {Journal of medical ultrasonics (2001)}, volume = {43}, number = {3}, pages = {387-394}, pmid = {27230095}, issn = {1613-2254}, mesh = {Biopsy ; Breast/*diagnostic imaging/pathology ; Breast Diseases/*diagnostic imaging/pathology ; Databases, Factual ; Diagnosis, Differential ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Physicians ; ROC Curve ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images.

METHODS: The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme.

RESULTS: The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045).

CONCLUSIONS: This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.}, } @article {pmid27226720, year = {2016}, author = {Mukherjee, SD and Hodgson, N and Lovrics, PJ and Dhamanaskar, K and Minuk, T and Chambers, S and Sussman, J}, title = {A Retrospective Study Evaluating the Impact of Preoperative Breast MRI on Surgical Decision-Making in Young Patients (≤50 Years) with Invasive Breast Cancer.}, journal = {Breast cancer : basic and clinical research}, volume = {10}, number = {}, pages = {53-60}, pmid = {27226720}, issn = {1178-2234}, abstract = {INTRODUCTION: Breast magnetic resonance imaging (MRI) is considered a more sensitive diagnostic test for detecting invasive breast cancer than mammography or breast ultrasound. Breast MRI may be particularly useful in younger premenopausal women with higher density breast tissue for differentiating between dense fibroglandular breast tissue and breast malignancies. The main objective of this study was to determine the impact of preoperative breast MRI on surgical decision-making in young women with breast cancer.

METHODS: A retrospective review of patients with newly diagnosed invasive breast cancer and age of ≤50 years was performed. All patients underwent physical examination, preoperative mammogram, breast ultrasound, and bilateral breast MRI. Two breast cancer surgeons reviewed the preoperative mammogram report, breast ultrasound report, and physical examination summary and were asked if they would recommend a lumpectomy, a quandrantectomy, or a mastectomy. A few weeks later, the two surgeons were shown the same information with the breast MRI report and were asked what type of surgery they would now recommend. In each case, MRI was classified by two adjudicators as having affected the surgical outcome in a positive, negative, or neutral fashion. A positive impact was defined as the situation where breast MRI detected additional disease that was not found on physical examination, mammogram, or breast ultrasound and led to an appropriate change in surgical management. A negative impact was defined as the situation where breast MRI led the surgeon to recommend more extensive surgery, with less extensive disease actually found at pathology. No impact was defined as the situation where MRI findings did not alter surgical recommendations or outcomes.

RESULTS: Of 37 patients whose charts were reviewed, five patients were deemed to be ineligible due to having received neoadjuvant chemotherapy, having previous breast implants, or having had their tumor fully excised during biopsy. In total, 32 patients met the inclusion criteria of this study and were appropriate for analysis. The median age of our study patient population was 42 years. The pathologic diagnosis was invasive ductal carcinoma in 91% (29/32) of patients and invasive lobular carcinoma in 9% (3/32) of patients. For surgeon A, clinical management was altered in 21/32 (66%) patients, and for surgeon B, management was altered in 13/32 (41%) patients. The most common change in surgical decision-making after breast MRI was from breast-conserving surgery to a mastectomy. Mastectomy rates were similar between both surgeons after breast MRI. After reviewing the pathology results and comparing them with the breast MRI results, it was determined that breast MRI led to a positive outcome in 13/32 (41%) patients. Breast MRI led to no change in surgical management in 15/32 (47%) patients and resulted in a negative change in surgical management in 4/32 (13%) patients. Bilateral breast MRI detected a contralateral breast cancer in 2/32 (6%) patients.

CONCLUSIONS: Preoperative breast MRI alters surgical management in a significant proportion of younger women diagnosed with breast cancer. Prospective studies are needed to confirm these findings and to help determine if this change in surgical decision-making will result in improved local control.}, } @article {pmid27222586, year = {2016}, author = {Min, KW and Kim, DH and Do, SI and Pyo, JS and Chae, SW and Sohn, JH and Kim, K and Lee, HJ and Kim, DH and Oh, S and Choi, SH and Park, YL and Park, CH and Kwon, MJ and Moon, KM}, title = {High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer.}, journal = {Postgraduate medical journal}, volume = {92}, number = {1094}, pages = {707-714}, doi = {10.1136/postgradmedj-2015-133531}, pmid = {27222586}, issn = {1469-0756}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Area Under Curve ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Lymph Node Excision ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tamoxifen/therapeutic use ; Tissue Array Analysis ; Trastuzumab/therapeutic use ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIMS: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker.

METHODS: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves.

RESULTS: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05).

CONCLUSIONS: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.}, } @article {pmid27221883, year = {2016}, author = {Effi, AB and Aman, NA and Koui, BS and Koffi, KD and Traore, ZC and Kouyate, M}, title = {Breast Cancer Molecular Subtypes Defined by ER/PR and HER2 Status: Association with Clinicopathologic Parameters in Ivorian Patients.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {4}, pages = {1973-1978}, doi = {10.7314/apjcp.2016.17.4.1973}, pmid = {27221883}, issn = {2476-762X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Cote d'Ivoire ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Premenopause ; Prognosis ; Prospective Studies ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast.

MATERIALS AND METHODS: Formalin- fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes.

RESULTS: Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1%) and non-luminal HER2+ (6.3%).

CONCLUSIONS: The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.}, } @article {pmid27212694, year = {2016}, author = {Sabatier, R and Sabiani, L and Zemmour, C and Taix, S and Chereau, E and Gonçalves, A and Jalaguier-Coudray, A and Charafe-Jauffret, E and Resbeut, M and Extra, JM and Viens, P and Tallet, A}, title = {Invasive ductal breast carcinoma with predominant intraductal component: Clinicopathological features and prognosis.}, journal = {Breast (Edinburgh, Scotland)}, volume = {27}, number = {}, pages = {8-14}, doi = {10.1016/j.breast.2015.12.003}, pmid = {27212694}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Tumor Burden ; }, abstract = {PURPOSE: Invasive ductal carcinoma with predominant intraductal component (IDCPIC) represents almost 5% of breast cancers. Nevertheless few data exist concerning their characteristics and prognostic behaviour. Our objective was to describe IDCPIC's clinicopathological and prognostic features and compare them to that of invasive ductal carcinoma without predominant intraductal component (IDC).

METHODS: Retrospective single centre study including all the localized invasive ductal carcinoma listed in our institutional database. Clinical, radiological and pathological criteria were collected as well as disease-free survival (DFS) data.

RESULTS: From 1995 to 2008, 4109 invasive ductal breast cancers treated were included. Out of them 192 (4.7%) were IDCPIC. Most of IDCPIC (63%) were discovered by radiological screening whereas IDC suspicion was more often clinical (82.7% vs 49.5%, p < 0.001). Pathological lymph node involvement was less frequent in IDCPIC (35.8 vs 44.3%, p = 0.04). Invasive tumour median size was 2-fold smaller in IDCPIC (10 mm vs 20 mm, p<0.001). Hormone receptors expression was similar between both groups whereas HER2 overexpression was more frequent in IDCPIC (32% vs 14.3%, p<0.001). Mastectomy was more frequently performed for IDCPIC (67.7% vs 30.3%, p < 0.001) whereas chemotherapy and radiation therapy were less frequent (55.5% vs 68%, and 82.8% vs 95.5%, respectively, p < 0.001 for both). After matching for discriminant clinicopathological features (tumour size, lymph node involvement, vascular invasion, HER2), DFS was similar in both groups (5-year DFS of 87.4% vs 84.4%, p = 0.47).

CONCLUSION: IDCPIC and other IDC with invasive components showing similar clinicopathological features display a similar prognosis.}, } @article {pmid27212693, year = {2016}, author = {Boisserie-Lacroix, M and Ziadé, C and Hurtevent-Labrot, G and Ferron, S and Brouste, V and Lippa, N}, title = {Is a one-year follow-up an efficient method for better management of MRI BI-RADS(®) 3 lesions?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {27}, number = {}, pages = {1-7}, doi = {10.1016/j.breast.2016.02.001}, pmid = {27212693}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Population Surveillance/*methods ; Retrospective Studies ; Time Factors ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {OBJECTIVES: To evaluate the necessity of a prolonged follow-up after one year for lesions incidentally diagnosed as Breast Imaging Reporting and Data System (BI-RADS)(®) 3 on magnetic resonance imaging (MRI).

METHODS: Institutional review board approved this study (CRC_june 2014_ project 11). We retrospectively analysed 218 consecutive MRI BI-RADS(®) 3 lesions in 110 women followed-up at 6, 12, 18 and/or 24 months from 2011 through to 2015. We excluded MRI scans of BRCA mutation carriers, in staging before treatment and in patients undergoing therapy for breast cancer. Second-look ultrasound and mammography were normal. We analysed 43 masses, 46 foci and 129 non-mass enhancements. In the follow-up, the image was scored as BI-RADS(®) 2 if it was completely resolved, BI-RADS(®) 3 if it was stable, and BI-RADS(®) 4 if a suspicious change occurred.

RESULTS: Forty-four lesions (20%) completely resolved during the follow-up. Six were scored as BI-RADS(®) 4: five at 6 months (benign) and one at 12 months (8 mm invasive ductal carcinoma). One hundred and sixty eight stable lesions were assigned BI-RADS(®) 2 at 18 or 24 months. The predictive positive value of cancer for BI-RADS(®) 3 lesions is 0.5% (95% CI [0.08-2.55]) in our study.

CONCLUSIONS: Our results suggest that a one year follow-up instead of two years is sufficient for BI-RADS 3 lesions, in case of using rigorous inclusion criteria. Given the very low PPV of the BI-RADS(®) 3 lesions incidentally found on MRI, further studies with very large inclusions are necessary to establish new guidelines for MRI follow-up.}, } @article {pmid27209064, year = {2016}, author = {Roggenbuck, D and Borghi, MO and Somma, V and Büttner, T and Schierack, P and Hanack, K and Grossi, C and Bodio, C and Macor, P and von Landenberg, P and Boccellato, F and Mahler, M and Meroni, PL}, title = {Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers.}, journal = {Arthritis research & therapy}, volume = {18}, number = {1}, pages = {111}, pmid = {27209064}, issn = {1478-6362}, mesh = {Adult ; Aged ; Antibodies, Antiphospholipid/*analysis ; Antiphospholipid Syndrome/*diagnosis/immunology ; Diagnosis, Differential ; Female ; Humans ; Immunoassay/*methods ; Infections/diagnosis/immunology ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).

METHODS: Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (β2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-β2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human β2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human β2GPI or after CL-micelle absorption.

RESULTS: Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM aß2GPI and aCL. Anti-CL and anti-ß2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and ß2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized β2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-β2GPI humoAbs.

CONCLUSIONS: The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.}, } @article {pmid27208304, year = {2016}, author = {Van Aken, O and De Clercq, I and Ivanova, A and Law, SR and Van Breusegem, F and Millar, AH and Whelan, J}, title = {Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases.}, journal = {Plant physiology}, volume = {171}, number = {3}, pages = {2150-2165}, pmid = {27208304}, issn = {1532-2548}, mesh = {Antimycin A/pharmacology ; Arabidopsis/drug effects/*physiology ; Arabidopsis Proteins/genetics/metabolism ; Chloroplasts/drug effects/*physiology ; Energy Metabolism/genetics ; Fluoroacetates/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Mitochondria/drug effects/*physiology ; Mitochondrial Proteins/genetics ; Plants, Genetically Modified ; Signal Transduction/drug effects ; Stress, Physiological/*physiology ; Transcription Factors/genetics/metabolism ; }, abstract = {Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control.}, } @article {pmid27184932, year = {2016}, author = {Desai, K and Nair, MG and Prabhu, JS and Vinod, A and Korlimarla, A and Rajarajan, S and Aiyappa, R and Kaluve, RS and Alexander, A and Hari, PS and Mukherjee, G and Kumar, RV and Manjunath, S and Correa, M and Srinath, BS and Patil, S and Prasad, MS and Gopinath, KS and Rao, RN and Violette, SM and Weinreb, PH and Sridhar, TS}, title = {High expression of integrin β6 in association with the Rho-Rac pathway identifies a poor prognostic subgroup within HER2 amplified breast cancers.}, journal = {Cancer medicine}, volume = {5}, number = {8}, pages = {2000-2011}, pmid = {27184932}, issn = {2045-7634}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*metabolism/mortality/pathology ; Female ; Gene Amplification ; Gene Expression ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Integrin beta Chains/*genetics ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Receptor, ErbB-2/genetics/*metabolism ; *Signal Transduction ; rac GTP-Binding Proteins/*metabolism ; }, abstract = {Integrin αvβ6 is involved in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast. In addition, integrin β6 (ITGB6) is of prognostic value in invasive breast cancers, particularly in HER2+ subtype. However, pathways mediating the activity of integrin αvβ6 in clinical progression of invasive breast cancers need further elucidation. We have examined human breast cancer specimens (N = 460) for the expression of integrin β6 (ITGB6) mRNA by qPCR. In addition, we have examined a subset (N = 147) for the expression of αvβ6 integrin by immunohistochemistry (IHC). The expression levels of members of Rho-Rac pathway including downstream genes (ACTR2, ACTR3) and effector proteinases (MMP9, MMP15) were estimated by qPCR in the HER2+ subset (N = 59). There is a significant increase in the mean expression of ITGB6 in HER2+ tumors compared to HR+HER2- and triple negative (TNBC) subtypes (P = 0.00). HER2+ tumors with the highest levels (top quartile) of ITGB6 have significantly elevated levels of all the genes of the Rho-Rac pathway (P-values from 0.01 to 0.0001). Patients in this group have a significantly shorter disease-free survival compared to the group with lower ITGB6 levels (HR = 2.9 (0.9-8.9), P = 0.05). The mean level of ITGB6 expression is increased further in lymph node-positive tumors. The increased regional and distant metastasis observed in HER2+ tumors with high levels of ITGB6 might be mediated by the canonical Rho-Rac pathway through increased expression of MMP9 and MMP15.}, } @article {pmid27183245, year = {2016}, author = {Yom-Tov, E and Brunstein-Klomek, A and Hadas, A and Tamir, O and Fennig, S}, title = {Differences in physical status, mental state and online behavior of people in pro-anorexia web communities.}, journal = {Eating behaviors}, volume = {22}, number = {}, pages = {109-112}, doi = {10.1016/j.eatbeh.2016.05.001}, pmid = {27183245}, issn = {1873-7358}, mesh = {Anorexia/*psychology ; Depression/epidemiology ; Female ; Humans ; *Internet ; Logistic Models ; Male ; Self-Injurious Behavior/*psychology ; Social Stigma ; Social Support ; Suicide/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: There is a debate about the effects of pro-anorexia (colloquially referred to as pro-ana) websites. Research suggests that the effect of these websites is not straightforward. Indeed, the actual function of these sites is disputed, with studies indicating both negative and positive effects.

AIM: This is the first study which systematically examined the differences between pro-anorexia web communities in four main aspects: web language used (posts); web interests/search behaviors (queries); users' self-reported weight status and weight goals; and associated self-reported mood/pathology.

METHODS: We collected three primary sources of data, including messages posed on three pro-ana websites, a survey completed by over 1000 participants of a pro-ana website, and the searches made on the Bing search engine of pro-anorexia users. These data were analyzed for content, reported demographics and pathology, and behavior over time.

RESULTS: Although members of the main pro-ana website investigated appear to be depressed, with high rates of self-harm and suicide attempts, users are significantly more interested in treatment, have wishes of procreation and reported the highest goal weights among the investigated sites. In contrast, users of other pro-ana websites investigated, are more interested in morbid themes including depression, self-harm and suicide. The percentage of severely malnourished website users, in general, appears to be small (20%).

CONCLUSIONS: Our results indicate that a new strategy is required to facilitate the communication between mental health specialists and pro-ana web users, recognizing the differences in harm associated with different websites.}, } @article {pmid27173185, year = {2016}, author = {Oliveira, NC and Gomig, TH and Milioli, HH and Cordeiro, F and Costa, GG and Urban, CA and Lima, RS and Cavalli, IJ and Ribeiro, EM}, title = {Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.}, journal = {Genetics and molecular research : GMR}, volume = {15}, number = {2}, pages = {}, doi = {10.4238/gmr.15027701}, pmid = {27173185}, issn = {1676-5680}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Proteome/*genetics/metabolism ; }, abstract = {Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.}, } @article {pmid27171095, year = {2016}, author = {Khan, MR and Khalilian, A and Kang, SW}, title = {A High Sensitivity IDC-Electronic Tongue Using Dielectric/Sensing Membranes with Solvatochromic Dyes.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {5}, pages = {}, pmid = {27171095}, issn = {1424-8220}, mesh = {Coloring Agents ; *Electronic Nose ; Glucose ; Reproducibility of Results ; *Taste ; Tongue ; }, abstract = {In this paper, an electronic tongue/taste sensor array containing different interdigitated capacitor (IDC) sensing elements to detect different types of tastes, such as sweetness (glucose), saltiness (NaCl), sourness (HCl), bitterness (quinine-HCl), and umami (monosodium glutamate) is proposed. We present for the first time an IDC electronic tongue using sensing membranes containing solvatochromic dyes. The proposed highly sensitive (30.64 mV/decade sensitivity) IDC electronic tongue has fast response and recovery times of about 6 s and 5 s, respectively, with extremely stable responses, and is capable of linear sensing performance (R[2] ≈ 0.985 correlation coefficient) over the wide dynamic range of 1 µM to 1 M. The designed IDC electronic tongue offers excellent reproducibility, with a relative standard deviation (RSD) of about 0.029. The proposed device was found to have better sensing performance than potentiometric-, cascoded compatible lateral bipolar transistor (C-CLBT)-, Electronic Tongue (SA402)-, and fiber-optic-based taste sensing systems in what concerns dynamic range width, response time, sensitivity, and linearity. Finally, we applied principal component analysis (PCA) to distinguish between various kinds of taste in mixed taste compounds.}, } @article {pmid27169108, year = {2016}, author = {Fakhrjou, A and Naghavi-Behzad, M and Montazeri, V and Karkon-Shayan, F and Norouzi-Panahi, L and Piri, R}, title = {The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration.}, journal = {South Asian journal of cancer}, volume = {5}, number = {1}, pages = {5-7}, pmid = {27169108}, issn = {2278-330X}, abstract = {INTRODUCTION: Breast carcinoma is the most prevalent tumors among women. Transformation of inflated cells in immune response leads to increase in inflammatory cells such as macrophages, mast cells (MC) and fibroblasts. The aim of this study was to determine the relationship between grades of invasive carcinoma of the breast ducts and MC infiltration around tumoral cells.

METHODS: During the present study, 75 female patients suffering from invasive ductal carcinoma who underwent surgery or diagnostic biopsy during 2010 and 2013 in Educational-Medical centers of Tabriz University of Medical Sciences, were included in the study. Based on Bloom-Richardson grading system, 25 cases were selected from each grade. To better observe of MCs, samples were stained by Toluidine blue and MCs were counted in 10 40 × 10 fields.

RESULTS: The mean age was 47.56 ± 10.84 and the number of MCs was between 6 and 96 and their overall average was 43.01. Average count of MCs in grade 1, 2 and 3 were 15.92 ± 10.07, 45.32 ± 10.47, and 67.8 ± 20.70, respectively. There was a significant relationship between the number of MCs and increase in disease grade (P < 0.001). With increasing grade of malignancy, the number of MCs had grown. No significant relationship was observed between age and grade of disease or age and number of MC.

CONCLUSION: According to obtained results, number of MC around tumoral cells increased significantly with an increase in the grade of disease. In order to treat in the first stages of the disease, recognizing primary changes in the stroma of cells could be helpful.}, } @article {pmid27168707, year = {2016}, author = {Madani, SH and Payandeh, M and Sadeghi, M and Motamed, H and Sadeghi, E}, title = {The correlation between Ki-67 with other prognostic factors in breast cancer: A study in Iranian patients.}, journal = {Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology}, volume = {37}, number = {2}, pages = {95-99}, pmid = {27168707}, issn = {0971-5851}, abstract = {CONTEXT: Despite the fact that breast cancer (BC) is a major health issue, very few studies describe its characteristics in the Middle East.

AIM: The aim of this study was to evaluate the use and value of Ki-67 as a prognostic marker in BC and associations between Ki-67, clinical, and histopathological parameters were evaluated.

SUBJECTS AND METHODS: In a retrospective study, 260 BC women and invasive ductal carcinoma were included to our study in Kermanshah city, Iran. Age, tumor size, lymph node involvement, histological grade, nuclear grade, and vascular invasion were other factors that determined in a lot of patients.

RESULTS: The mean age at diagnosis was 47.6 years (range, 24-84 years) with 100% female. Of 243 patients that tumor size was determined for them, 207 patients (85.2%) had tumor size ≥2 cm, and 36 patients (14.8%) had size <2 cm and also of 237 patients, 47 patients (19.8%), 140 (59.1%), and 50 (21.1%) had histological grades I, II, and III, respectively. There is significant correlation between Ki-67 with nuclear grade, human epidermal growth factor receptor 2 (HER2), and p53 (P < 0.05). Based on this result, more patients with Ki-67 ≥20% have higher nuclear grade, p53-positive, and HER2-positive. There was correlation between Ki-67 with type of tumor (P = 0.009).

CONCLUSIONS: The higher Ki-67 has a direct significant correlation with higher nuclear grade, p53-positive, and HER2-positive. Furthermore, triple negative patients have higher Ki-67 compared to other subtypes.}, } @article {pmid27161340, year = {2016}, author = {Zalsman, G and Shoval, G and Mansbach-Kleinfeld, I and Farbstein, I and Kanaaneh, R and Lubin, G and Apter, A}, title = {Maternal versus adolescent reports of suicidal behaviors: a nationwide survey in Israel.}, journal = {European child & adolescent psychiatry}, volume = {25}, number = {12}, pages = {1349-1359}, pmid = {27161340}, issn = {1435-165X}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Depressive Disorder/psychology ; Female ; *Health Surveys/standards ; Humans ; Israel/epidemiology ; Male ; Mothers/*psychology ; Prevalence ; Residence Characteristics ; Risk Factors ; *Self Report/standards ; Stress Disorders, Post-Traumatic/epidemiology/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; }, abstract = {Community and nationwide surveys on adolescent suicidal behaviors using clinical interviews are not abundant. Rates of self-reported suicide attempts in community samples vary greatly between 1 and 20 %. In general, adolescent and parental agreement in child psychiatry practice is low, and their agreement with regard to suicidal behavior is unknown. The current study assesses the rates of suicidal ideation and behaviors as well as the rate of agreement between adolescents and their mothers in a representative nationwide sample. The survey included a representative and randomized community sample of 14- to 17-year-old adolescents (n = 957), and their mothers who were interviewed using the Development and Well-Being Assessment Inventory (DAWBA). The prevalence of suicidal ideation and self-initiated behaviors was 4.9 and 1.9 %, respectively. The concordance between mothers' and adolescents' reporting on ideation was low (7.3 %). There was no concordance between mothers' and adolescents' reports of suicidal acts. Adolescents reported self-initiated behaviors nearly three times more frequently than their mothers. Paternal unemployment, care by welfare agencies and having a psychiatric disorder, specifically depression or post-traumatic stress disorder, was associated with a higher risk for both suicidal ideation and attempts. In this nationwide community study, by evaluating information gathered by clinical interviews, it was found that the lifetime rates of suicidal ideation were moderate. The rates of suicide attempts were lower than have been previously reported. The concordance between the reports of adolescents and their mothers was low for ideation and nonexistent for attempts. Thus, clinicians should interview adolescents separately from their mothers regarding their suicidality.}, } @article {pmid27160778, year = {2016}, author = {Han, Y and Wang, S and Hibshoosh, H and Taback, B and Konofagou, E}, title = {Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI).}, journal = {Breast cancer research : BCR}, volume = {18}, number = {1}, pages = {46}, pmid = {27160778}, issn = {1465-542X}, support = {R01 EB014496/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/therapy ; Female ; Fibroadenoma/diagnostic imaging/pathology/therapy ; *High-Intensity Focused Ultrasound Ablation/methods ; Humans ; Imaging, Three-Dimensional ; Middle Aged ; Postoperative Care ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive technique used in the treatment of early-stage breast cancer and benign tumors. To facilitate its translation to the clinic, there is a need for a simple, cost-effective device that can reliably monitor HIFU treatment. We have developed harmonic motion imaging (HMI), which can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely harmonic motion imaging for focused ultrasound (HMIFU). The overall objective of this study was to develop an all ultrasound-based system for real-time imaging and ablation monitoring in the human breast in vivo.

METHODS: HMI was performed in 36 specimens (19 normal, 15 invasive ductal carcinomas, and 2 fibroadenomas) immediately after surgical removal. The specimens were securely embedded in a tissue-mimicking agar gel matrix and submerged in degassed phosphate-buffered saline to mimic in vivo environment. The HMI setup consisted of a HIFU transducer confocally aligned with an imaging transducer to induce an oscillatory radiation force and estimate the resulting displacement.

RESULTS: 3D HMI displacement maps were reconstructed to represent the relative tissue stiffness in 3D. The average peak-to-peak displacement was found to be significantly different (p = 0.003) between normal breast tissue and invasive ductal carcinoma. There were also significant differences before and after HMIFU ablation in both the normal (53.84 % decrease) and invasive ductal carcinoma (44.69 % decrease) specimens.

CONCLUSIONS: HMI can be used to map and differentiate relative stiffness in postsurgical normal and pathological breast tissues. HMIFU can also successfully monitor thermal ablations in normal and pathological human breast specimens. This HMI technique may lead to a new clinical tool for breast tumor imaging and HIFU treatment monitoring.}, } @article {pmid27158121, year = {2016}, author = {Erro, R and Picillo, M and Vitale, C and Palladino, R and Amboni, M and Moccia, M and Pellecchia, MT and Barone, P}, title = {Clinical clusters and dopaminergic dysfunction in de-novo Parkinson disease.}, journal = {Parkinsonism & related disorders}, volume = {28}, number = {}, pages = {137-140}, doi = {10.1016/j.parkreldis.2016.04.026}, pmid = {27158121}, issn = {1873-5126}, mesh = {Aged ; Cluster Analysis ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*classification/*metabolism/*physiopathology ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {BACKGROUND: The heterogeneity of PD suggests the existence of different subtypes. While some motor clusters have been consistently identified, little is known about non-motor PD subtypes and motor-non-motor interplay. Research in this regard has produced somewhat contradictory results, which might be biased by the inclusion of treated patients.

PATIENTS AND METHODS: We performed a non-hierarchical cluster analysis using both motor and non-motor data on 398 newly diagnosed untreated PD patients enrolled in the Parkinson's Progressive Marker Initiative (PPMI) study. We further evaluated whether dopaminergic dysfunction, as measured by (123)[I]-FP-CIT SPECT scan, could explain, at least partially, the observed difference between the clusters.

RESULTS: Three clusters were identified. Group 1 was characterized by the lowest motor and non-motor burden, whereas group 2 and 3 had similar motor disability, but different non-motor involvement, especially with regards to apathy and hallucinations. (123)[I]-FP-CIT binding values paralleled motor disability burden among the 3 clusters, but further multivariate analyses also revealed a negative correlation with depression.

DISCUSSION: Our results confirm the motor as well as non-motor heterogeneity of PD, suggesting the existence of 3 different subtypes. Dopaminergic dysfunction only marginally explains the non-motor variability of PD. Identification of such clusters can have important implications for generating novel pathophysiological hypotheses and therapeutic strategies.}, } @article {pmid27156133, year = {2016}, author = {Santos, CS and Carvalho, SM and Leite, A and Moniz, T and Roriz, M and Rangel, AO and Rangel, M and Vasconcelos, MW}, title = {Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.).}, journal = {Plant physiology and biochemistry : PPB}, volume = {106}, number = {}, pages = {91-100}, doi = {10.1016/j.plaphy.2016.04.050}, pmid = {27156133}, issn = {1873-2690}, mesh = {Biomass ; Chlorophyll/metabolism ; FMN Reductase/metabolism ; Ferric Compounds/*pharmacology ; Gene Expression Regulation, Plant/drug effects ; Iron/*metabolism ; Iron Chelating Agents/chemistry/pharmacology ; Ligands ; Lipid Peroxidation/drug effects ; Malondialdehyde/metabolism ; Minerals/metabolism ; Plant Development/drug effects ; Plant Diseases ; Plant Leaves/drug effects/metabolism ; Plant Proteins/genetics/metabolism ; Plant Roots/metabolism ; Plant Shoots/drug effects/metabolism ; Pyridines/*pharmacology ; Soybeans/drug effects/genetics/*metabolism ; Spectrum Analysis ; }, abstract = {Iron deficiency chlorosis (IDC) is a serious environmental problem affecting the growth of several crops in the world. The application of synthetic Fe(III) chelates is still one of the most common measures to correct IDC and the search for more effective Fe chelates remains an important issue. Herein, we propose a tris(3-hydroxy-4-pyridinonate) iron(III) complex, Fe(mpp)3, as an IDC corrector. Different morphological, biochemical and molecular parameters were assessed as a first step towards understanding its mode of action, compared with that of the commercial fertilizer FeEDDHA. Plants treated with the pyridinone iron(III) complexes were significantly greener and had increased biomass. The total Fe content was measured using ICP-OES and plants treated with pyridinone complexes accumulated about 50% more Fe than those treated with the commercial chelate. In particular, plants supplied with compound Fe(mpp)3 were able to translocate iron from the roots to the shoots and did not elicit the expression of the Fe-stress related genes FRO2 and IRT1. These results suggest that 3,4-HPO iron(III) chelates could be a potential new class of plant fertilizing agents.}, } @article {pmid27154986, year = {2016}, author = {Jove, M and Verghese, E and Sharma, N and Lane, S}, title = {Residual mucin and response after neoadjuvant chemotherapy (NAC) in breast cancer.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, pmid = {27154986}, issn = {1757-790X}, mesh = {Adenocarcinoma, Mucinous/*drug therapy/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism ; Female ; Humans ; Lymph Nodes/metabolism ; Middle Aged ; Mucins/*metabolism ; Neoadjuvant Therapy/*methods ; Treatment Outcome ; }, abstract = {Neoadjuvant chemotherapy (NAC) is the standard of care for patients with breast cancer with inoperable disease or smaller tumours who might benefit from a conservative surgery after downstaging of their disease. Nevertheless, evidence shows that preoperative and postoperative chemotherapy are equivalent in terms of long-term survival. Response and histological changes after NAC have been widely studied in invasive ductal carcinoma not otherwise specified, but there is a paucity of characterisation of patterns of response to chemotherapy in less frequent histological types. We report extensive residual mucin deposits after chemotherapy in a woman with locally advanced breast cancer and a prominent mucinous component at diagnosis. Interestingly, residual mucin was co-located with the initial tumour, in the breast as well as in the axillary lymph nodes. The distribution of mucin may be a valuable marker of the extent of mucinous carcinomas prior to NAC.}, } @article {pmid27153443, year = {2017}, author = {Chatterjee, D and Bal, A and Das, A and Kohli, PS and Singh, G and Mittal, BR}, title = {Invasive Duct Carcinoma of the Breast With Dominant Signet-Ring Cell Differentiation: A Microsatellite Stable Tumor With Aggressive Behavior.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {25}, number = {10}, pages = {720-724}, doi = {10.1097/PAI.0000000000000366}, pmid = {27153443}, issn = {1533-4058}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Signet Ring Cell/*diagnosis/pathology ; DNA-Binding Proteins/genetics ; Female ; Humans ; Immunohistochemistry ; Microsatellite Repeats/genetics ; Middle Aged ; MutS Homolog 2 Protein/genetics ; Prognosis ; }, abstract = {AIMS: Invasive duct carcinoma, no special type (IDC, NST), of the breast with signet-ring cell differentiation is uncommon. This study was undertaken to describe the clinicopathologic characteristics of IDC, NST, with dominant signet-ring cell differentiation, and look for microsatellite instability in these tumors.

METHODS: Cases of IDC, NST, with dominant signet-ring cell differentiation, diagnosed over the past 2 years, were retrieved. Detailed clinical and pathologic analyses were performed. Immunohistochemistry was performed for estrogen receptor, progesterone receptors, Her-2 neu, Ki-67, E-cadherin, CK7, and CK20. Microsatellite instability was examined using immunohistochemistry for the 4 mismatch repair proteins: MLH1, MSH2, MSH6, and PMS2.

RESULTS: Of the total 1646 cases of IDC, NST, only 5 cases showed dominant signet-ring cells (ranging from 70% to 100%) and strong E-cadherin positivity and were diagnosed as IDC, NST, with dominant signet-ring cell differentiation. The age ranged from 32 to 65 years. Two cases were of histologic grade 3 and the remaining cases were grade 2 tumors. Four patients had T2 tumor and 1 had T3 tumor. All cases had axillary lymph node metastasis and distant metastasis was present in 1 case. All cases were microsatellite stable.

CONCLUSIONS: Signet-ring cell differentiation in IDC, NST, is rare and associated with a high histologic grade. Lymph node metastasis and distant metastasis are common, indicating an aggressive clinical behavior. Thus, they should be recognized separately as they may warrant aggressive management. However, these are microsatellite-stable tumors in contrast to signet-ring cell tumors of other organs.}, } @article {pmid27148582, year = {2016}, author = {Brannon, AR and Frizziero, M and Chen, D and Hummel, J and Gallo, J and Riester, M and Patel, P and Cheung, W and Morrissey, M and Carbone, C and Cottini, S and Tortora, G and Melisi, D}, title = {Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus.}, journal = {Cold Spring Harbor molecular case studies}, volume = {2}, number = {2}, pages = {a000620}, pmid = {27148582}, issn = {2373-2873}, abstract = {The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER(+)/HER2(-) metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR(+))/HER2(-) stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR(+) female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.}, } @article {pmid27148087, year = {2016}, author = {Doron, G and Derby, D and Szepsenwol, O and Nahaloni, E and Moulding, R}, title = {Relationship Obsessive-Compulsive Disorder: Interference, Symptoms, and Maladaptive Beliefs.}, journal = {Frontiers in psychiatry}, volume = {7}, number = {}, pages = {58}, pmid = {27148087}, issn = {1664-0640}, abstract = {BACKGROUND: Obsessive preoccupation, doubts, and compulsive behaviors focusing on one's romantic relationship and partner are receiving increasing clinical, theoretical, and empirical attention. Commonly referred to as relationship obsessive-compulsive disorder (ROCD), such symptoms have been linked with decreased relational and sexual functioning and lower mood, even after controlling for other obsessive-compulsive disorder (OCD) symptoms. To date, however, these symptoms have been studied in community samples alone. In the present study, we compared levels of interference, OCD, and mood symptoms between clinical participants with ROCD, OCD, and community controls. We also examined group differences in maladaptive beliefs previously linked with OCD and ROCD.

METHOD: Participants included 22 ROCD clients, 22 OCD clients, and 28 community controls. The Mini International Neuropsychiatric Interview was used to attain clinical diagnoses of OCD and ROCD. The Yale-Brown Obsessive-Compulsive Scale was used to evaluate primary-symptoms severity. All participants completed measures of symptoms and dysfunctional beliefs.

RESULTS: ROCD clients reported more severe ROCD symptoms than the OCD and control groups. ROCD and OCD clients did not differ in severity of their -primary-symptoms. ROCD clients scored higher than the other groups on maladaptive OCD-related and relationship-related beliefs. Finally, ROCD clients showed more severe depression symptoms than community controls.

CONCLUSION: ROCD is a disabling presentation of OCD that warrants research attention. Maladaptive OCD-related and relationship-related beliefs may be implicated in the development and maintenance of ROCD.}, } @article {pmid27146735, year = {2016}, author = {Krishnamurthy, J and Kumar, PS}, title = {Significance of prognostic indicators in infiltrating duct carcinoma breast: Scenario in developing country.}, journal = {Indian journal of cancer}, volume = {53}, number = {1}, pages = {34-38}, doi = {10.4103/0019-509X.180834}, pmid = {27146735}, issn = {1998-4774}, mesh = {Adult ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Developing Countries ; Female ; Humans ; Middle Aged ; Prognosis ; }, abstract = {CONTEXT: Carcinoma of the breast is one of the most common malignant tumors and is the most common cause of death from cancers in females. Early diagnosis and assessing the prognosis for each patient is essential for a better therapeutic plan and management.

AIMS: To evaluate the significance of various prognostic indicators of breast carcinoma by correlating with Nottingham modification of Scarff Bloom-Richardson's grading system (NMBGS).

MATERIALS AND METHODS: Eighty four patients who underwent mastectomy for breast carcinoma at a tertiary care centre in South India over a period of 2 years have been evaluated to note the importance of the various prognostic factors correlating them with NMBGS.

STATISTICAL ANALYSIS: A Chi-square test was used to determine possible association between the various prognostic factors.

RESULTS: Eighty percent of the tumors were infiltrating ductal carcinoma (IDC), and it is seen that the larger tumor size, higher histopathological grade, increased lymphovascular invasion, lymphnode metastasis, tumor necrosis, microvessel density, estrogen and progesterone receptor negativity, and HER-2/neu positivity were associated with higher grade of tumor.

CONCLUSIONS: The traditional morphological factors including the histological type, grade, tumor size, lymphovascular invasion, lymph node status, presence of necrosis, stromal reaction, and microvascular density (MVD) count are relatively simple but robust prognostic factors to assess, while the hormonal and genetic status not only have prognostic value but are useful predictive marker for adjuvant chemotherapy. Hence, the status of these various prognostic factors should form the basis of all routine histopathological reports in cases of breast cancer for better management.}, } @article {pmid27145402, year = {2016}, author = {Tessitore, A and Giordano, A and De Micco, R and Caiazzo, G and Russo, A and Cirillo, M and Esposito, F and Tedeschi, G}, title = {Functional connectivity underpinnings of fatigue in "Drug-Naïve" patients with Parkinson's disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {31}, number = {10}, pages = {1497-1505}, doi = {10.1002/mds.26650}, pmid = {27145402}, issn = {1531-8257}, mesh = {Aged ; Cerebral Cortex/diagnostic imaging/*physiopathology ; Connectome/*methods ; Fatigue/diagnostic imaging/etiology/*physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease/complications/diagnostic imaging/*physiopathology ; }, abstract = {INTRODUCTION: Fatigue is a common problem in PD either in the early or later stage of the disease. Using resting-state functional MRI, we investigated the functional correlates of fatigue in a cohort of "drug-naïve" patients with PD.

METHODS: MRI at 3Tesla was collected in 40 patients with PD, 20 with and 20 without fatigue, and 20 matched healthy controls. Presence and the severity of fatigue were defined based on the 16-item Parkinson fatigue scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting state networks between patients subgroups and healthy controls. In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences.

RESULTS: Distressing fatigue was associated with a decreased connectivity in the supplementary motor area within the sensorimotor network and an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (P < 0.05 corrected). Fatigue severity was correlated with both sensorimotor and default mode networks connectivity changes. Voxel-based morphometry analysis did not reveal any significant volume differences between all patients with PD and healthy controls and between patients with PD with and without fatigue (P < 0.05; family-wise error).

CONCLUSIONS: Our findings revealed that primary PD-related fatigue is associated with an altered default mode network and sensorimotor network connectivity in drug-naïve patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. © 2016 International Parkinson and Movement Disorder Society.}, } @article {pmid27137487, year = {2016}, author = {Fuhrmeister, J and Zota, A and Sijmonsma, TP and Seibert, O and Cıngır, Ş and Schmidt, K and Vallon, N and de Guia, RM and Niopek, K and Berriel Diaz, M and Maida, A and Blüher, M and Okun, JG and Herzig, S and Rose, AJ}, title = {Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.}, journal = {EMBO molecular medicine}, volume = {8}, number = {6}, pages = {654-669}, pmid = {27137487}, issn = {1757-4684}, mesh = {Animals ; Cell Cycle Proteins/*metabolism ; *Fasting ; Fatty Acid-Binding Proteins/metabolism ; Fatty Acids/*metabolism ; Liver/*metabolism ; Mice ; Mice, Knockout ; Nuclear Proteins/*metabolism ; }, abstract = {Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function.}, } @article {pmid27134710, year = {2016}, author = {Abudu, EK and Akinbami, OS}, title = {Cancers in Young Patients in Uyo (Niger-delta Region of Nigeria): Magnitude of the Problem and Histopathological Prolife.}, journal = {Rare tumors}, volume = {8}, number = {1}, pages = {6124}, pmid = {27134710}, issn = {2036-3605}, abstract = {Cancers are thought to be rarer in younger population, but emerging data show an increasing incidence of these diseases. The aim of this study was to evaluate the clinicopathological characteristics of cancer among young patients (≥30 years) in Uyo, Nigeria. All specimens were collected and reviewed during the period January 2007-December 2012; complete clinicopathological data were also considered. A total of 108 cases of proven cancers were diagnosed (3.4%), accounting for 14.1% of all malignancies. A male:female ratio of 1:3.2 was recorded. Among 0-14-year-old patients, the most common malignancy was embryonal cancer (50.0%), followed by non-Hodgkin's lymphoma (18.8%). Carcinoma of the breast and soft tissue sarcoma represent first and second cancers in those patients (40.7% and 13.0% respectively). Carcinoma of uterine cervix and nodal lymphomas were the third and fourth most common cancers respectively (10.2% and 7.4%), significantly higher in the 21-30 years and 0-10 years age groups. Invasive ductal carcinoma, squamous cell carcinoma, Kaposi sarcoma and Hodgkin's lymphoma were the most common histologic types of cancers in breast, uterine cervix, lymph node and soft tissue (79.6%, 90.0%, 44.4%, 50.0% respectively). This study shows that embryonal cancer was the most common malignancy in patients aged 0 to 14, while carcinoma of the breast and soft tissue sarcoma were the two most common cancers in patients from 5 to 30 years-old.}, } @article {pmid27130444, year = {2016}, author = {Brunstein Klomek, A and Nakash, O and Goldberger, N and Haklai, Z and Geraisy, N and Yatzkar, U and Birnai, A and Levav, I}, title = {Completed suicide and suicide attempts in the Arab population in Israel.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {51}, number = {6}, pages = {869-876}, pmid = {27130444}, issn = {1433-9285}, mesh = {Adolescent ; Adult ; Arabs/*statistics & numerical data ; Christianity ; Female ; Humans ; Islam ; Israel/ethnology ; Male ; Middle Aged ; Suicide/*ethnology ; Suicide, Attempted/ethnology ; Young Adult ; }, abstract = {Completed suicide and suicide attempts among four Arab groups defined by religious affiliation in Israel: Bedouins, Muslims (other than Bedouin), Christians and Druze were investigated using national databases of suicide (1999-2011), and suicide attempts (2004-2012). Age specific and age-adjusted rates and ratio of suicides to suicidal behavior were calculated, and compared with the total Israeli population rates. Age-adjusted suicide rates were lowest among the non-Bedouin Muslims, 2.5, followed in ascending order by Bedouins, 3.2, and Christian Arabs, 3.3 per 100,000 population, respectively. The highest rate was found among the Druze, 8.7, per 100,000 population, particularly for young males. The rates among the Arab groups were lower than for the total Israeli population, 7.9 per 100,000 population, except for the Druze. The pattern of suicide rates by gender, higher for males than females, was similar in all groups. The rates among the Arab Israelis were highest for the 15-24 year old age group, while in the total population the rates increased with age. Age-adjusted suicide attempt rates were higher amongst non-Bedouin Muslims, 84.8 per 100,000 population, followed by the Bedouin, 72.4; Druze. 64.9; and lowest among Christian Arabs, 58.6, all per 100,000 population. In the total Israeli population, the rate was even higher, 89.8 per 100,000 population. Suicide attempt rates were higher for women in all groups, except among the Druze. Rates were higher in most groups for ages 15-24. In this age group, the rates for female Muslims and Bedouins and for male Druze were higher than among the total population. Arab elderly had low rates of both suicide and suicide attempts. The ratio of suicides to suicide attempts increased with age for all groups, except for the Christian Arabs. It was markedly higher for the Druze, compared to 7.3 % for the total population for ages 15 and over. Findings highlight the importance of investigating the differential distribution of suicidal behavior by specific ethno-religious groups.}, } @article {pmid27125354, year = {2016}, author = {Yao, M and Yu, E and Staggs, V and Fan, F and Cheng, N}, title = {Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {8}, pages = {810-823}, pmid = {27125354}, issn = {1530-0285}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology/therapy ; Calcium-Binding Proteins/analysis ; Carcinoma, Ductal, Breast/*chemistry/pathology/therapy ; Carcinoma, Lobular/*chemistry/pathology/therapy ; Chemokine CCL2/*analysis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Risk Factors ; S100 Calcium-Binding Protein A4 ; Stromal Cells/*chemistry/pathology ; Time Factors ; Tissue Array Analysis ; Treatment Outcome ; Tumor Burden ; Tumor Microenvironment ; Up-Regulation ; }, abstract = {Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n=427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR=7.51 P=0.007) was associated with a greater hazard than cancer stage (HR=2.45, P=0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with important implications on the use of stromal markers for predicting patient prognosis.}, } @article {pmid27123296, year = {2016}, author = {He, T and Liu, J and Li, Y and Jin, LU and Sun, S and Ni, L and Mao, X and Yang, S and Lai, Y}, title = {Left adrenal gland metastasis of breast invasive ductal carcinoma: A case report.}, journal = {Molecular and clinical oncology}, volume = {4}, number = {5}, pages = {859-862}, pmid = {27123296}, issn = {2049-9450}, abstract = {The majority of the metastatic lesions of the adrenal gland normally originate from lung cancer, colon malignant tumor, renal cell carcinoma and melanoma. However, adrenal gland metastasis that metastasize from breast invasive ductal carcinoma are extremely rare. The present study reported a rare case of left adrenal gland metastasis in a 35-year-old female who was diagnosed as breast carcinoma 5 years ago with a mass located on the left adrenal gland, which was detected during a routine examination. The patient was asymptomatic and adrenal gland computed tomography revealed a mass in the left adrenal gland. Definitive preoperative diagnosis failed to be established. Left adrenal gland laparoscopic adrenalectomy was performed and the diagnosis of adrenal gland metastasis of breast invasive ductal carcinoma was confirmed by pathological and immunohistochemical examination. The patient remained in good condition by the time of writing.}, } @article {pmid27123269, year = {2016}, author = {Ouyang, Q and Tian, C and Gao, J and Huang, J and Fu, H and He, J and Yang, J}, title = {HER2-positive double primary tumor of gastric and breast cancer occur synchronously in a patient: A case report.}, journal = {Molecular and clinical oncology}, volume = {4}, number = {5}, pages = {719-722}, pmid = {27123269}, issn = {2049-9450}, abstract = {The simultaneous occurrence of primary gastric cancer and breast cancer is rare, and the positive expression of human epidermal growth factor receptor (HER)2 in double primary carcinoma of gastric and breast cancer remains to be reported. The present study presented a 46-year-old woman complaining of irregular acid reflux and stomach discomfort. The stomach cancer was diagnosed by esophagogastroduodenoscopy examination of the pathological biopsies in 2010. The patient underwent a radical gastrectomy for gastric cancer, and postoperative pathological examination revealed moderately-poorly differentiated adenocarcinoma with HER2 positive expression. The tumor invaded into the entire thickness of the gastric wall and lymph nodes. The patient received five treatments of postoperative chemotherapy. In August 2011, the patient felt a lump in the right breast. Simple excision of the right breast mass was performed on September 2011, and postoperative pathological examination revealed the invasive ductal carcinoma of the right breast with HER2 amplification by fluorescent in situ hybridization assay. The patient was treated with postoperative chemotherapy and radiotherapy, and also Trastuzumab target therapy. The patient succumbed to aggressive disease progression in March 2012.}, } @article {pmid27123098, year = {2016}, author = {Fama', F and Licata, L and Villari, A and Palella, J and Speciale, G and Gioffre'-Florio, M}, title = {Late recurrent cutaneous breast angiosarcoma in an elderly woman: A case report.}, journal = {Oncology letters}, volume = {11}, number = {5}, pages = {3247-3250}, pmid = {27123098}, issn = {1792-1074}, abstract = {Breast angiosarcomas are malignant tumours of the vascular endothelium that arise frequently following radiation therapy. Their clinical and radiological aspects are highly heterogeneous. The current study reports an unusual case, never previously reported, of a late recurrent breast angiosarcoma occurring in an 83-year old female patient 11 years after a breast-conserving surgery followed by radiation therapy for an invasive ductal carcinoma, and 5 years after her initial angiosarcoma excision. The first physician to examine the patient noted a palpable mass near the scar and, following ultrasonography, described the breast lesion as suggestive of an abscess, despite the previous history of neoplasia. Typically, recurrences of breast angiosarcoma occur within the first postsurgical year. The present patient remains alive at 25 months after her last surgical treatment, and no evidence of any local or distant disease is observable.}, } @article {pmid27123064, year = {2016}, author = {Kiba, T and Morii, N and Takahashi, H and Ozaki, S and Atsumi, M and Masumoto, F and Yamashiro, H}, title = {Pathological complete response rate in hormone receptor-negative breast cancer treated with neoadjuvant FEC, followed by weekly paclitaxel administration: A retrospective study and review of the literature.}, journal = {Oncology letters}, volume = {11}, number = {5}, pages = {3064-3070}, pmid = {27123064}, issn = {1792-1074}, abstract = {While tumor size, the presence of inflammatory carcinoma and lymph node involvement are the main prognostic factors of women with locally advanced breast cancer, the prognostic value of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status has not been fully clarified. The present study examined the therapeutic efficacy of a neoadjuvant fluorouracil, epirubicin and cyclophosphamide regimen (FEC), followed by weekly paclitaxel and/or trastuzumab administration, in the treatment of hormone receptor-negative breast cancer patients. Between April 2012 and February 2014, 14 patients with hormone receptor-negative local breast cancer (triple-negative type, 9 patients; HER2 type, 5 patients) were included in the study. In all cases, the histological type of the primary cancer was invasive ductal carcinoma. Among the 14 women who received the regimen, 5 presented with stage I cancer (35.7%), 3 with stage IIA (21.4%), 3 with stage IIB (21.4%), 1 with stage IIIB (7.1%) and 2 with stage IIIC (14.3%), according to the American Joint Committee on Cancer staging system. With regard to the tumor-node-metastasis classification, 5 patients were T1N0M0 (35.7%), 3 were T2N0M0 (21.4%), 3 were T2N1M0 (21.4%), 2 were T3N3M0 (14.3%) and 1 was T4N1M0 (7.1%). The pathological response was evaluated using resected tissue following neoadjuvant chemotherapy, according to the criteria established by the Japanese Breast Cancer Society. Patients were classified into pathological responders (grades 2 and 3, 71.4% of all patients) and non-responders (grade 1, 28.6% of all patients). A pathological complete response (pCR) was achieved in 50.0% of all cases (7/14); 44.4% of triple-negative-type cases (4/9) and 60.0% of HER2-type cases (3/5). Hematological and non-hematological toxicity was reversible and manageable. No patients withdrew from treatment, and favorable compliance was achieved. The present study demonstrated that neoadjuvant FEC followed by weekly administration of paclitaxel and/or trastuzumab induces a high pathological response and a high pCR rate in patients with hormone receptor-negative breast cancer. Due to the high clinical benefit rate and acceptable safety profile, this regimen should be considered an acceptable neoadjuvant treatment option for hormone receptor-negative breast cancer.}, } @article {pmid27121067, year = {2016}, author = {Lobbezoo, D and Truin, W and Voogd, A and Roumen, R and Vreugdenhil, G and Dercksen, MW and van den Berkmortel, F and Smilde, T and van de Wouw, A and van Kampen, R and van Riel, J and Peters, N and Peer, P and Tjan-Heijnen, VC}, title = {The role of histological subtype in hormone receptor positive metastatic breast cancer: similar survival but different therapeutic approaches.}, journal = {Oncotarget}, volume = {7}, number = {20}, pages = {29412-29419}, pmid = {27121067}, issn = {1949-2553}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*drug therapy/mortality ; Carcinoma, Ductal, Breast/*drug therapy/mortality ; Carcinoma, Lobular/*drug therapy/mortality ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Treatment Outcome ; }, abstract = {INTRODUCTION: This study describes the differences between the two largest histological breast cancer subtypes (invasive ductal carcinoma (IDC) and invasive (mixed) lobular carcinoma (ILC) with respect to patient and tumor characteristics, treatment-choices and outcome in metastatic breast cancer.

RESULTS: Patients with ILC were older at diagnosis of primary breast cancer and had more often initial bone metastasis (46.5% versus 34.8%, P = 0.01) and less often multiple metastatic sites compared to IDC (23.7% versus 30.9%, P = 0.11). Six months after diagnosis of metastatic breast cancer, 28.1% of patients with ILC and 39.8% of patients with IDC had received chemotherapy with a longer median time to first chemotherapy for those with ILC (P = 0.001). After six months 84.8% of patients with ILC had received endocrine therapy versus 72.5% of patients with IDC (P = 0.0001). Median overall survival was 29 months for ILC and 25 months for IDC (P = 0.53).

MATERIALS AND METHODS: We included 437 patients with hormone receptor-positive IDC and 131 patients with hormone receptor-positive ILC, all diagnosed with metastatic breast cancer between 2007-2009, irrespective of date of the primary diagnosis. Patient and tumor characteristics and data on treatment and outcome were collected. Survival curves were obtained using the Kaplan-Meier method.

CONCLUSIONS: Treatment strategies of hormone receptor-positive metastatic breast cancer were remarkably different for patients with ILC and IDC. Further research is required to understand tumor behavior and treatment-choices in real-life.}, } @article {pmid27118712, year = {2016}, author = {Tang, R and Coopey, SB and Merrill, AL and Rai, U and Specht, MC and Gadd, MA and Colwell, AS and Austen, WG and Brachtel, EF and Smith, BL}, title = {Positive Nipple Margins in Nipple-Sparing Mastectomies: Rates, Management, and Oncologic Safety.}, journal = {Journal of the American College of Surgeons}, volume = {222}, number = {6}, pages = {1149-1155}, doi = {10.1016/j.jamcollsurg.2016.02.016}, pmid = {27118712}, issn = {1879-1190}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Margins of Excision ; Mastectomy, Subcutaneous/*methods ; Middle Aged ; Nipples/pathology/*surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: When a nipple margin of a nipple-sparing mastectomy (NSM) contains malignancy, current practice includes removal of the nipple or nipple areola complex (NAC). We evaluated rates and trends of positive nipple margins, subsequent management, and oncologic outcomes.

STUDY DESIGN: A retrospective chart review of all NSM at our institution from 2007 to 2014 was performed. A descriptive analysis was performed of patients with positive nipple/subareolar margins.

RESULTS: Among 1,326 NSM, 43 of 642 (6.7%) therapeutic and 3 of 684 (0.4%) prophylactic NSM had positive nipple margins. Nipple or NAC excision was performed for 39 of 46 (85%) positive nipple margins: 20 of 39 (51%) had nipple only and 19 of 39 (49%) had the entire NAC excised. Practice evolved to remove only the nipple and retain the areola for positive nipple margins: in 2007 to 2011, 7 of 17 (41%) underwent nipple-only excision compared with 14 of 22 (64%) in 2012 to 2014. Among 39 excised nipples/NAC, 28 (72%) contained no residual malignancy, while 8 contained ductal carcinoma in situ (DCIS), 2 had invasive lobular carcinoma, and 1 had invasive ductal carcinoma. With experience, rates of positive nipple margins for therapeutic NSM decreased from 11% (17 of 160) in 2007 to 2011 to 5.4% (26 of 482) in 2012 to 2014 (p < 0.05). At 36 month median follow-up, there were no recurrences in the nipple/NAC.

CONCLUSIONS: Early results suggest that excision of the nipple with retention of the areola is a safe approach for management of a positive nipple margin after NSM. With experience, low rates of positive nipple margins are possible in therapeutic NSM. Overall risk of nipple/NAC recurrence after NSM remains extremely low.}, } @article {pmid27116948, year = {2016}, author = {Truin, W and Roumen, RM and Siesling, S and van der Heiden-van der Loo, M and Lobbezoo, DJ and Tjan-Heijnen, VC and Voogd, AC}, title = {Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer.}, journal = {Clinical breast cancer}, volume = {16}, number = {4}, pages = {e75-82}, doi = {10.1016/j.clbc.2016.03.007}, pmid = {27116948}, issn = {1938-0666}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Lobular/diagnosis/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Sentinel Lymph Node/*pathology/surgery ; *Sentinel Lymph Node Biopsy ; Standard of Care ; }, abstract = {BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification outcomes. We evaluated the effect of axillary staging procedures and subsequent axillary nodal status in patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) from 1998 to 2013.

MATERIALS AND METHODS: The use of SLN biopsy and the nodal status distribution were analyzed in patients with stage T1-T2 ILC and IDC. Logistic regression analysis was performed to determine the independent effect of histologic type on the probability of the presence of isolated tumor cells (ITCs), micrometastases, and macrometastases.

RESULTS: A total of 89,971 women were diagnosed, 10,146 with ILC (11%) and 79,825 with IDC (89%). The patients who had undergone SLN biopsy were more frequently diagnosed with ITCs than were those who had undergone axillary lymph node dissection only (odds ratio, 8.8; 95% confidence interval, 7.0-11.2). In 2013, the proportion of patients with ITCs in the axillary nodes was 8% in those with ILC and 4.4% in those with IDC. Patients with ILC were significantly more likely to have ITCs in their axillary lymph nodes than were patients with IDC (odds ratio, 1.8; 95% confidence interval, 1.6-2.0).

CONCLUSION: With the introduction of SLN biopsy and the renewed 2002 TNM classification, patients with ILC have been more frequently diagnosed with ITCs than have patients with IDC. The clinical consequence of this finding must be established from further research.}, } @article {pmid27116366, year = {2016}, author = {Dobbs, JL and Shin, D and Krishnamurthy, S and Kuerer, H and Yang, W and Richards-Kortum, R}, title = {Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.}, journal = {International journal of cancer}, volume = {139}, number = {5}, pages = {1140-1149}, doi = {10.1002/ijc.30160}, pmid = {27116366}, issn = {1097-0215}, mesh = {Adipocytes/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal/*pathology ; Carcinoma, Ductal, Breast/immunology/pathology ; Female ; Humans ; *Microscopy, Confocal/methods ; *Tumor Microenvironment ; }, abstract = {Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.}, } @article {pmid27097912, year = {2016}, author = {Costello, LC and Zou, J and Franklin, RB}, title = {In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma.}, journal = {Cancer causes & control : CCC}, volume = {27}, number = {6}, pages = {729-735}, pmid = {27097912}, issn = {1573-7225}, support = {R01 CA079903/CA/NCI NIH HHS/United States ; R01 CA093443/CA/NCI NIH HHS/United States ; R01 DK042839/DK/NIDDK NIH HHS/United States ; R01 DK076763/DK/NIDDK NIH HHS/United States ; }, mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Case-Control Studies ; Chelating Agents ; Dithizone ; Female ; Humans ; Zinc/*metabolism ; }, abstract = {PURPOSE: Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells.

METHODS: We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies.

RESULTS: The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium.

CONCLUSIONS: The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the mechanisms and factors regarding the regulation of zinc in breast cancer, its potential translational applications as possible biomarkers, and for treatment of breast invasive ductal carcinoma.}, } @article {pmid27092808, year = {2017}, author = {Giarenis, I and Zacchè, M and Robinson, D and Cardozo, L}, title = {Is there any association between urodynamic variables and severity of overactive bladder in women with idiopathic detrusor overactivity?.}, journal = {Neurourology and urodynamics}, volume = {36}, number = {3}, pages = {780-783}, doi = {10.1002/nau.23023}, pmid = {27092808}, issn = {1520-6777}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Severity of Illness Index ; Urinary Bladder/*physiopathology ; Urinary Bladder, Neurogenic/complications/diagnosis/*physiopathology ; Urinary Bladder, Overactive/complications/diagnosis/*physiopathology ; Urinary Incontinence/diagnosis/etiology/*physiopathology ; Urodynamics/*physiology ; }, abstract = {AIMS: The lack of a validated detrusor overactivity (DO) severity tool limits the clinical value of urodynamics in the management of patients with overactive bladder syndrome (OAB). The aim of this study, was to identify urodynamic variables that correlate with validated OAB severity measures.

METHODS: This was a cross-sectional study enrolling consecutive women with idiopathic DO. The 24 hr urgency episodes and the score of the Incontinence Impact (II) domain of the King's Health Questionnaire (KHQ) were used to assess the severity of OAB.

RESULTS: The study enrolled 299 women with idiopathic DO. The cystometric capacity, compliance, and the threshold volume for the first involuntary detrusor contraction (IDC) showed a statistically significant negative correlation with the II domain of the KHQ and the 24 hr urgency episodes. There was a statistically significant positive correlation between the amplitude of first IDC and the OAB severity measures, but only borderline for the amplitude of the highest IDC. There were no statistically significant differences between women with and without leakage per urethram during a detrusor contraction.

CONCLUSIONS: Cystometric capacity, compliance (measured in ml/cm H2 O), threshold volume, and amplitude of the first IDC could be routinely documented in everyday clinical practice. The measures more commonly used for describing the severity of DO, such as leakage per urethram during a detrusor contraction and amplitude of the highest detrusor contraction, have a limited role confirming the complicated interaction between the detrusor muscle, the urethral sphincter, and the pelvic floor in women. Neurourol. Urodynam. 36:780-783, 2017. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27087373, year = {2016}, author = {Yang, T and Zhang, ZP and Sun, XY and Liu, G and Mu, DB and Wang, YS}, title = {[Shrinkage mode of the primary breast tumor after neoadjuvant chemotherapy analyzed with part-mount sub-serial sectioning and three-dimensional reconstruction technique].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {38}, number = {4}, pages = {270-276}, doi = {10.3760/cma.j.issn.0253-3766.2016.04.006}, pmid = {27087373}, issn = {0253-3766}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Lymph Nodes/pathology ; Multivariate Analysis ; *Neoadjuvant Therapy ; Neoplasm, Residual ; Software ; Tomography, X-Ray Computed ; Tumor Burden/*drug effects ; }, abstract = {OBJECTIVE: The aim of this study is to evaluate the shrinkage mode of the primary tumor in women with breast cancer after neoadjuvant chemotherapy (NAC) determined by part-mount sub-serial section (PMSS) and three-dimensional (3D) reconstruction technique.

METHODS: Eighty-six women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. They were divided into two groups. Group A (n=25) received half cycles of NAC and Group B (n=61) received whole cycles of NAC. Breast specimen was prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of residual tumors was reconstructed with 3D-Doctor software to evaluate the shrinkage mode. Further, the clinicpathologic shrinkage modes were divided into 2 categories: concentric shrinkage mode (CSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC), and non-concentric shrinkage mode (NCSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).

RESULTS: Pathological shrinkage modes: Group A: modes Ⅰ, Ⅱ, and Ⅴ were observed in 1, 1, and 23 cases, respectively; Group B: modesⅠ, Ⅱ, Ⅲ, Ⅳ, and Ⅴwere observed in 18, 3, 12, 21, and 7 cases, respectively (P<0.001). The multivariate analysis showed that patients with lower primary tumor stage, PR(-) or mammographic malignant calcification before NAC(-) and lymph nodes down-staging after NAC were more likely to present with CSM after NAC (P<0.05 for all).

CONCLUSIONS: The pathologic reconstruction of breast residual tumors can fully and three-dimensionally reveal the shrinkage mode of the primary breast tumor in women with breast cancer after NAC. PMSS and 3D reconstruction of pathology provide a new platform in this area. Primary tumor stage, PR expression and mammographic malignant calcification before NAC and lymph node down-staging after NAC are independent predictors of the clinicopathologic shrinkage mode.}, } @article {pmid27083750, year = {2016}, author = {Dong, J and Si, W and Wu, CQ}, title = {Drift of charge carriers in crystalline organic semiconductors.}, journal = {The Journal of chemical physics}, volume = {144}, number = {14}, pages = {144905}, doi = {10.1063/1.4945778}, pmid = {27083750}, issn = {1089-7690}, abstract = {We investigate the direct-current response of crystalline organic semiconductors in the presence of finite external electric fields by the quantum-classical Ehrenfest dynamics complemented with instantaneous decoherence corrections (IDC). The IDC is carried out in the real-space representation with the energy-dependent reweighing factors to account for both intermolecular decoherence and energy relaxation by which conduction occurs. In this way, both the diffusion and drift motion of charge carriers are described in a unified framework. Based on an off-diagonal electron-phonon coupling model for pentacene, we find that the drift velocity initially increases with the electric field and then decreases at higher fields due to the Wannier-Stark localization, and a negative electric-field dependence of mobility is observed. The Einstein relation, which is a manifestation of the fluctuation-dissipation theorem, is found to be restored in electric fields up to ∼10(5) V/cm for a wide temperature region studied. Furthermore, we show that the incorporated decoherence and energy relaxation could explain the large discrepancy between the mobilities calculated by the Ehrenfest dynamics and the full quantum methods, which proves the effectiveness of our approach to take back these missing processes.}, } @article {pmid27081649, year = {2016}, author = {Al-Ameer, AY and Al Nefaie, S and Al Johani, B and Anwar, I and Al Tweigeri, T and Tulbah, A and Alshabanah, M and Al Malik, O}, title = {Sentinel lymph node biopsy in clinically detected ductal carcinoma in situ.}, journal = {World journal of clinical oncology}, volume = {7}, number = {2}, pages = {258-264}, pmid = {27081649}, issn = {2218-4333}, abstract = {AIM: To study the indications for sentinel lymph node biopsy (SLNB) in clinically-detected ductal carcinoma in situ (CD-DCIS).

METHODS: A retrospective analysis of 20 patients with an initial diagnosis of pure DCIS by an image-guided core needle biopsy (CNB) between June 2006 and June 2012 was conducted at King Faisal Specialist Hospital. The accuracy of performing SLNB in CD-DCIS, the rate of sentinel and non-sentinel nodal metastasis, and the histologic underestimation rate of invasive cancer at initial diagnosis were analyzed. The inclusion criteria were a preoperative diagnosis of pure DCIS with no evidence of invasion. We excluded any patient with evidence of microinvasion or invasion. There were two cases of mammographically detected DCIS and 18 cases of CD-DCIS. All our patients were diagnosed by an image-guided CNB except two patients who were diagnosed by fine needle aspiration (FNA). All patients underwent breast surgery, SLNB, and axillary lymph node dissection (ALND) if the SLN was positive.

RESULTS: Twenty patients with an initial diagnosis of pure DCIS underwent SLNB, 2 of whom had an ALND. The mean age of the patients was 49.7 years (range, 35-70). Twelve patients (60%) were premenopausal and 8 (40%) were postmenopausal. CNB was the diagnostic procedure for 18 patients, and 2 who were diagnosed by FNA were excluded from the calculation of the underestimation rate. Two out of 20 had a positive SLNB and underwent an ALND and neither had additional non sentinel lymph node metastasis. Both the sentinel visualization rate and the intraoperative sentinel identification rate were 100%. The false negative rate was 0%. Only 2 patients had a positive SLNB (10%) and neither had additional metastasis following an ALND. After definitive surgery, 3 patients were upstaged to invasive ductal carcinoma (3/18 = 16.6%) and 3 other patients were upstaged to DCIS with microinvasion (3/18 = 16.6%). Therefore the histologic underestimation rate of invasive disease was 33%.

CONCLUSION: SLNB in CD-DCIS is technically feasible and highly accurate. We recommend limiting SLNB to patients undergoing a mastectomy.}, } @article {pmid27080531, year = {2016}, author = {Chabot, V and Martin, L and Meley, D and Sensebé, L and Baron, C and Lebranchu, Y and Dehaut, F and Velge-Roussel, F}, title = {Unexpected impairment of TNF-α-induced maturation of human dendritic cells in vitro by IL-4.}, journal = {Journal of translational medicine}, volume = {14}, number = {}, pages = {93}, pmid = {27080531}, issn = {1479-5876}, mesh = {Biomarkers/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; Cell Differentiation/*drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Chemokines/pharmacology ; Dendritic Cells/*cytology/drug effects/metabolism ; Humans ; Interleukin-12/metabolism ; Interleukin-4/metabolism ; Lymphocyte Activation/drug effects ; RNA, Messenger/genetics/metabolism ; Receptors, CCR7/genetics/metabolism ; Th1 Cells/drug effects ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {BACKGROUND: An efficient strategy for programming dendritic cells (DCs) for cancer immunotherapy is the optimization of their maturation so that they can efficiently stimulate cancer-specific T cell responses. Interleukin (IL)-4 has appeared as an essential cytokine, widely used in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) to differentiate monocytes into immature DCs (iDC) and to prevent macrophage formation. Conflicting data have been published regarding the effect of IL-4 on functional DC maturation. To further understand IL-4's effects on DC maturation and function in vitro, we choose the most commonly used maturation factor tumor necrosis factor (TNF)-α.

METHODS: Human monocyte-derived iDC were treated for 48 h with GM-CSF and TNF-α in the presence (IL-4(+)-DC) or absence (IL-4(-)-DC) of IL-4 and functions of both DC populations were compared.

RESULTS: On mixed lymphocyte reaction assay, IL-4(+)-DC were less potent than IL-4(-)-DC at inducing the proliferation of allogeneic CD4(+) T cells and the proportion of activated T cells expressing CD69 and/or CD25 was smaller. Interleukin-4 reduced the cell-surface expression of TNF-α-induced DC maturation markers CD83, CD86, HLA-DR and CD25 and generated a heterogeneous population of DCs. IL-4(+)-DC secreted less IL-12 and more IL-10 than IL-4(-)-DC following activation by soluble CD40L, and IL-4(+)-DC-activated T cells secreted lesser amounts of T helper (Th) 1 cytokines (IL-2 and interferon-γ). Importantly, IL-4 impaired the in vitro migratory capacity of DCs in response to CCL21 and CCL19 chemokines. This effect was related to reduced expression of CCR7 at both mRNA and protein levels.

CONCLUSION: Interleukin-4 used with GM-CSF and TNF-α during the maturation of DCs in vitro impaired DC functions and disturbed the maturation effect of TNF-α. Finally, our study reinforces the view that the quality of the DC maturation stimulus, which regulates DC migration and cytokine production, may be a decisive feature of the immunogenicity of DCs.}, } @article {pmid27076454, year = {2016}, author = {Pai, T and Shet, T and Desai, S and Patil, A and Nair, N and Parmar, V and Gupta, S and Budrukkar, A and Sarin, R and Badwe, R}, title = {Impact of Squamous Differentiation in Breast Carcinoma.}, journal = {International journal of surgical pathology}, volume = {24}, number = {6}, pages = {483-489}, doi = {10.1177/1066896916642290}, pmid = {27076454}, issn = {1940-2465}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Squamous Cell/mortality/*pathology ; Cell Differentiation ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Metaplasia/pathology ; Middle Aged ; }, abstract = {This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing <40% squamous elements and worse for those with >90% squamous component (P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis.}, } @article {pmid27073510, year = {2016}, author = {Shibata, S and Shiraishi, K and Yamashita, H and Kobayashi, R and Nakagawa, K}, title = {Radiation-induced low-grade fibromyxoid sarcoma of the chest wall nine years subsequent to radiotherapy for breast carcinoma: A case report.}, journal = {Oncology letters}, volume = {11}, number = {4}, pages = {2520-2524}, pmid = {27073510}, issn = {1792-1074}, abstract = {The present study reports a case of low-grade fibromyxoid sarcoma that occurred in a 62-year-old woman 9 years subsequent to whole breast irradiation for a carcinoma of the left breast, and 18 years following chemotherapy and radiotherapy (RT) for non-Hodgkin's lymphoma (NHL; diagnosed at the age of 43). The patient was 53 years of age when a cT2N0M0 stage IIA breast tumor was identified and excised. A 2.5 cm diameter nodule with dimpling in the upper-outer region of the left breast was detected. Pathological examination revealed that the tumor was an invasive ductal carcinoma, of a solid tubular type. The patient was treated with post-surgical whole breast RT. The left breast received 46 Gy in 23 fractions (2 Gy per fraction) for 4 weeks and 3 days, followed by a cone down boost of 14 Gy in 7 fractions (2 Gy per fraction); therefore a total dose of 60 Gy in 30 fractions was administered. In total, 9 years subsequent to RT, the patient observed a small lump in the left chest wall. The patient underwent excision of the tumor and pectoralis major fascia. Microscopically, the tumor consisted of atypical spindle cells with myxoid stroma. Pathologists concluded that the tumor was a low-grade fibromyxoid sarcoma. Since the tumor developed from tissue in a previously irradiated region, it was considered to be RT-induced, and was classified using the radiation-induced sarcoma (RIS) criteria as dictated by Cahan. Although the majority of RIS cases are angiosarcomas, a rare, low-grade fibromyxoid sarcoma was observed in the present study. The present study hypothesizes that there may have been an overlap region between the RT for supraclavicular nodes of NHL and the whole breast RT for primary breast cancer, due to the results of a retrospective dose reconstruction undertaken by the present study. The patient remained clinically stable for 4 years thereafter, until 2008 when the patient experienced a local relapse and underwent surgery. On 19 October 2011, the patient succumbed to RIS. The current study suggests that the RT history of a patient requires consideration due to the possible development of RIS, including the development of a low-grade fibromyxoid sarcoma, which may lead to a poor prognosis.}, } @article {pmid27073506, year = {2016}, author = {Wu, DI and Zhang, H and Guo, L and Yan, XU and Fan, Z}, title = {Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature.}, journal = {Oncology letters}, volume = {11}, number = {4}, pages = {2502-2506}, pmid = {27073506}, issn = {1792-1074}, abstract = {Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor.}, } @article {pmid27067853, year = {2016}, author = {Ooe, A and Suganuma, Y}, title = {[Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {43}, number = {3}, pages = {349-351}, pmid = {27067853}, issn = {0385-0684}, mesh = {Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration & dosage ; Breast Neoplasms/*drug therapy/*pathology ; Capecitabine/*therapeutic use ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Paclitaxel/administration & dosage ; Salvage Therapy ; }, abstract = {We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.}, } @article {pmid27066847, year = {2016}, author = {Picillo, M and Palladino, R and Moccia, M and Erro, R and Amboni, M and Vitale, C and Barone, P and Pellecchia, MT}, title = {Gender and non motor fluctuations in Parkinson's disease: A prospective study.}, journal = {Parkinsonism & related disorders}, volume = {27}, number = {}, pages = {89-92}, doi = {10.1016/j.parkreldis.2016.04.001}, pmid = {27066847}, issn = {1873-5126}, mesh = {Aged ; Antiparkinson Agents/therapeutic use ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Levodopa/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/*diagnosis/drug therapy/*epidemiology ; Prospective Studies ; *Sex Characteristics ; }, abstract = {INTRODUCTION: In Parkinson's disease (PD), non motor symptoms can fluctuate either along or irrespective to motor on/off phenomena. Prospective studies suggest that higher motor scores and levodopa dosage, younger age at onset and female gender represent risk factors for motor fluctuations' development. Yet, the predictors of development of non motor fluctuations (NMF) are less clear. In this prospective study, we aimed to assess the relationship between NMF and gender along with other potential risk factors.

METHODS: Forty-seven (16 women/31 men) de novo, drug-naïve PD patients have been followed for 4 years since diagnosis. Motor and non motor fluctuations were evaluated with the 19-item Wearing off Questionnaire (WOQ-19). The association between gender and NMF was explored with multivariable regression models adjusted for age at onset, motor and non motor symptoms at diagnosis and levodopa intake at follow up.

RESULTS: Female gender was more likely associated with a diagnosis of NMF (adjusted odds ratio, AOR = 5.33,95%CI = 1.21-23.4, p = 0.027), but not with a diagnosis of generic wearing off at follow up (OR = 3.66, 95%CI = 0.8-16.8, p = 0.097). Women had greater likelihood of developing higher WOQ-19 Non motor scores (AOR = 4.58, 95%CI = 1.23-17.03, p = 0.023), but not higher WOQ-19 Total scores (AOR = 2.88, 95%CI = 0.86-9.71, p = 0.087) compared to men. Notwithstanding, no gender differences were detected in medication intake.

CONCLUSIONS: We showed that female gender represents a major risk factor for the development of NMF. There were no gender differences in medication intake, thus NMF in women remain mostly underestimated and not properly treated. From a practical standpoint, clinicians should take into account the role of gender in the management of NMF in PD.}, } @article {pmid27066096, year = {2016}, author = {Jang, SH and Lee, JE and Oh, MH and Lee, JH and Cho, HD and Kim, KJ and Kim, SY and Han, SW and Kim, HJ and Bae, SB and Lee, HJ}, title = {High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer.}, journal = {Journal of breast cancer}, volume = {19}, number = {1}, pages = {53-60}, pmid = {27066096}, issn = {1738-6756}, abstract = {PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance.

METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed.

RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045).

CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.}, } @article {pmid27065772, year = {2016}, author = {Shakeri, H and Gharesouran, J and Fakhrjou, A and Esfahani, A and Mohaddes Ardebili, SM}, title = {DNA methylation assessment as a prognostic factor in invasive breast cancer using methylation-specific multiplex ligation dependent probe amplification.}, journal = {EXCLI journal}, volume = {15}, number = {}, pages = {11-20}, pmid = {27065772}, issn = {1611-2156}, abstract = {DNA methylation of promoter regions is a common molecular mechanism for inactivation of tumor suppressor genes that participates in carcinogenesis. Determining the methylation status of genes in cancer and their association with clinical features play an essential role in early diagnosis, prognosis and determine appropriate treatment for patients. The purpose of the present study was to evaluate the methylation of tumor suppressor genes in patients with invasive ductal carcinoma (IDC). Furthermore, we evaluated the association between clinical parameters and DNA methylation as a biomarker in diagnostic IDC patients. The methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) assay was used to analyze the methylation profile of 24 genes in formalin-fixed paraffin embedded (FFPE) tissue samples from 75 patients with IDC. Each of the patients showed a distinctive methylation profile. We observed higher methylation in the RASSF1 (48 %), CDH13 (44 %) and GSTP1 (36 %) genes. Some of the methylated genes were associated with clinical features. Methylation of GSTP1 (P=0.028) and RASSF1 (P=0.012) were related with lymph node metastasis. Methylation of GSTP1 (P=0.005) was associated with high histological grade. Moreover, concurrent methylation of GSTP1 and CDH13 was observed in IDC patients (p<0.001). Hierarchical cluster analysis based on the methylation profile revealed two main clusters of patients, the highly methylated cluster being significantly associated with high histological grade and lymph node metastasis. The results of this study indicate that the methylation status of RASSF1 and CDH13 and GSTP1 can be a prognostic marker to better management of IDC patients.}, } @article {pmid27065666, year = {2015}, author = {Sundriyal, D and Kotwal, S and Dawar, R and Parthasarathy, KM}, title = {Male Breast Cancer in India: Series from a Cancer Research Centre.}, journal = {Indian journal of surgical oncology}, volume = {6}, number = {4}, pages = {384-386}, pmid = {27065666}, issn = {0975-7651}, abstract = {Male breast cancer (MBC) is an uncommon malignancy. The scarcity of cases has reduced the focus of research in this area as compared with female breast cancer. The incidence of breast cancer in males is slowly rising and it becomes important to study the biology of this uncommon illness. Aim of the present work was to study the clinico-pathological behaviour of male breast cancer at a cancer research institute in India. 18 cases of MBC were identified out of 1752 cases of breast cancer registered during a 10 year period. Clinical parameters and histopathological data were analysed. MBC comprised of 1.03 % of total breast cancer cases. Median age of presentation was 60 years. Most of the patients presented to us in advanced stage. Aggressive pattern of disease was recognised with high node positivity, more perineural spread and lymphovascular invasion. Most of the cases were positive for hormone receptors. Breast cancer is seen at a relatively early age in Indian males. Disease is aggressive in nature with high hormone receptor positivity.}, } @article {pmid27053333, year = {2016}, author = {Zheng, YZ and Hu, X and Shao, ZM}, title = {Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {24037}, pmid = {27053333}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Papillary/*epidemiology/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Survival Analysis ; Young Adult ; }, abstract = {To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥ 50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289-1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients.}, } @article {pmid27050973, year = {2016}, author = {Zhao, L and Zhang, QY and Luan, X and Huang, X and Zhao, S and Zhao, H}, title = {Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma.}, journal = {Genetics and molecular research : GMR}, volume = {15}, number = {1}, pages = {}, doi = {10.4238/gmr.15017464}, pmid = {27050973}, issn = {1676-5680}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Enhancer of Zeste Homolog 2 Protein/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Middle Aged ; Prognosis ; Receptor, Notch1/genetics/*metabolism ; }, abstract = {We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2 months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.}, } @article {pmid27047724, year = {2016}, author = {Kim, EM and Hankins, A and Cassity, J and McDonald, D and White, B and Rowberry, R and Dutton, S and Snyder, C}, title = {Isolated radial scar diagnosis by core-needle biopsy: Is surgical excision necessary?.}, journal = {SpringerPlus}, volume = {5}, number = {}, pages = {398}, pmid = {27047724}, issn = {2193-1801}, abstract = {PURPOSE: Radial scar and radial sclerosis (RS) are considered benign breast lesions with proliferative features. There is sparse literature on frequency of cancer upgrade in these patients without atypical features found on image-guided needle biopsy. This study retrospectively reviews cases of isolated RS diagnosed on needle biopsy and evaluates the cancer upgrade after subsequent surgical excision.

METHODS: We conducted a retrospective cross-sectional study of cases with an isolated RS diagnosis based on needle biopsy and subsequent surgical pathology among all patients between January 1, 2009 and December 31, 2013. Patients with concomitant atypia, lobular carcinoma in situ on core biopsy, complete excision of very small RS with needle biopsy, and radiology-pathology discordance were excluded. An upgrade from the needle biopsy of RS was defined as surgical excision pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and/or invasive lobular carcinoma (ILC).

RESULTS: 10,921 image-guided needle biopsy pathology reports were collected and 88 patients (0.81 %) were identified as having isolated RS. Of these 88 patients, 63 (72 %) underwent excision. The upgrade rate to cancer on subsequent surgical excision was 1.59 % (1/63) for DCIS; 0 % (0/63) for IDC; and 0 % (0/63) ILC. Twenty-five patients who did not undergo surgical excision had stable imaging studies with mean (±SD) 26 (±20) months follow up.

CONCLUSIONS: Isolated radial scar on needle biopsy may not warrant routine surgical excision given relatively low cancer upgrade rates. Advancement in breast imaging, pathology and multidisciplinary approaches to care may effectively guide non-surgical management of RS.}, } @article {pmid27041932, year = {2016}, author = {Chen, N and Zhou, Q}, title = {Intraductal carcinoma of prostate (IDC-P): from obscure to significant.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {28}, number = {1}, pages = {99-106}, pmid = {27041932}, issn = {1000-9604}, abstract = {The concept of intraductal carcinoma of prostate (IDC-P) has evolved over the years and its clinicopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraductal lesions that represent earlier stages of the malignant process in other anatomic sites such as the breast, IDC-P has now been generally recognized as a prognostically unfavorable manifestation of later stage spreading of its invasive counterpart. We here briefly review the evolution of the IDC-P concept, the histological diagnostic criteria and differential diagnosis, the clinical significance, as well as recent molecular data of IDC-P.}, } @article {pmid27041335, year = {2016}, author = {Lim, ST and Choi, JE and Kim, SJ and Kim, HA and Kim, JY and Park, HK and Suh, YJ}, title = {Prognostic implication of the tumor location according to molecular subtypes in axillary lymph node-positive invasive ductal cancer in a Korean population.}, journal = {Breast cancer research and treatment}, volume = {156}, number = {3}, pages = {473-483}, doi = {10.1007/s10549-016-3771-6}, pmid = {27041335}, issn = {1573-7217}, mesh = {Adult ; Axilla ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/genetics ; Registries ; Republic of Korea ; Retrospective Studies ; }, abstract = {Previous studies have not considered the axillary lymph node status when investigating the prognostic role of tumor location according to each molecular subtype. The present study aimed to investigate the prognostic implication of tumor location according to each molecular subtype in Korean invasive ductal carcinoma (IDC) patients with axillary lymph node metastasis. Data from 7856 Korean IDC women with axillary lymph node metastasis were retrospectively analyzed. According to tumor location, patients were divided into the following groups: upper-outer quadrant, lower-outer quadrant, upper-inner quadrant, lower-inner quadrant (LIQ), and central group. Overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated according to tumor location and molecular subtype. A subgroup analysis based on tumor size categorization was also performed. The patients' mean age was 47.97 ± 9.64 years, and the median follow-up time was 90 months. The LIQ group showed significantly worse prognosis in OS and BCSS (76.4 and 83.3 %, respectively) compared with the other groups, which was only significant in human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative (TN) subtypes. In the subgroup analysis according to tumor size, the LIQ group showed a significantly worse prognosis in OS and BCSS compared with the other groups, in HER2 and TN subtypes, and only in patients with more than T2 stage. In Korean IDC patients with axillary lymph node metastasis, LIQ tumor location was associated with poor prognosis among those with HER2 and TN molecular subtypes and especially in those with more than T2 stage.}, } @article {pmid27040931, year = {2016}, author = {Rarick, J and Kimler, BF and Tawfik, O}, title = {Comparison of margin status and lesional size between radioactive seed localized vs conventional wire localized breast lumpectomy specimens.}, journal = {Annals of diagnostic pathology}, volume = {21}, number = {}, pages = {47-52}, doi = {10.1016/j.anndiagpath.2016.01.003}, pmid = {27040931}, issn = {1532-8198}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Iodine Radioisotopes ; Margins of Excision ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; }, abstract = {Despite the known benefits of the use of radioactive seed localization (RSL), few studies have looked at the resultant pathologic marginal status of these lumpectomy specimens, especially in regard to different definitions of close/positive margins. We compared the marginal status of lumpectomy specimens removed by either RSL or conventional wire localization (CWL) techniques. A total of 106 lumpectomy specimens including 62 by CWL and 44 by RSL for invasive ductal and lobular carcinomas were compared. Data on gross and microscopic surgical margin status, tumor type and grade, and demographic information were retrospectively collected. There was no difference between the techniques in terms of tumor characteristics including size, histologic grade, lymph node positivity, or age. Although the distributions are very similar between CWL and RSL specimens for final marginal assessments (P=.69), there is a (modest) statistically significant difference in the distribution for margin classifications based on gross assessments (P=.040), specifically more RSL specimens exhibiting tumor within 1mm of the closest margin. Concordance between gross and microscopic lesion measurements is highest for invasive ductal carcinoma grade 3 for both CWL and RSL lumpectomies (78.6% and 80.0%). This study shows that there were no significant marginal status differences between RSL and CWL lumpectomy specimens with invasive carcinoma. Rather, what was relevant is whether the entire specimen could be classified as having negative/close margins. Significant workflow challenges in surgical pathology laboratories are expected with the adoption of the RSL process.}, } @article {pmid27040042, year = {2016}, author = {Jacob, JD and Hodge, C and Franko, J and Pezzi, CM and Goldman, CD and Klimberg, VS}, title = {Rare breast cancer: 246 invasive secretory carcinomas from the National Cancer Data Base.}, journal = {Journal of surgical oncology}, volume = {113}, number = {7}, pages = {721-725}, doi = {10.1002/jso.24241}, pmid = {27040042}, issn = {1096-9098}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; *Breast Neoplasms/diagnosis/epidemiology/pathology/therapy ; *Carcinoma/diagnosis/epidemiology/pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Survival Analysis ; Treatment Outcome ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Invasive secretory breast carcinoma (SBC) is a rare subtype of breast malignancy.

METHODS: Cases of SBC and infiltrating ductal carcinoma (IDC) from the National Cancer Database (1998-2011) were queried.

RESULTS: Patients with SBC (n = 246) and IDC were identified (n = 1,564,068). The group with SBC was younger (age 56.4 ± 16.0 vs. 60.4 ± 13.9 years, P < 0.001), had similar tumor size (19.9 ± 17.8 vs. 21.6 ± 25.5 mm, P = 0.297), more frequently African-Americans (24.1 vs. 14.8 vs. 13.7; P = 0.004), more well-differentiated (32 vs. 18%, P < 0.001) and less likely to be hormone receptor positive (ER: 64 vs. 76%, P = 0.001; PR: 43 vs. 65%, P < 0.001). No differences were found for incidence of node-positivity (32 vs. 34%, P = 0.520) and stage IV presentation (2.4 vs. 3.6%, P = 0.372). Breast conserving surgery (60 vs. 58%, P = 0.405) and hormonal therapy (67 vs. 71%, P = 0.489) rates were similar. Systemic chemotherapy was used less often for SBC (38 vs. 45%, P = 0.035). The overall survival of all patients with SBC was better than all patients with IDC (median not reached vs. 14.8 years, P = 0.025).

CONCLUSION: SBC is an uncommon tumor that is often well-differentiated and seen in younger women. Contrary to prior reports, they are frequently hormone receptor-positive. Compared to IDC, overall survival is improved. J. Surg. Oncol. 2016;113:721-725. © 2016 Wiley Periodicals, Inc.}, } @article {pmid27039751, year = {2016}, author = {Yadav, P and Mir, R and Nandi, K and Javid, J and Masroor, M and Ahmad, I and Zuberi, M and Kaza, R and Jain, S and Khurana, N and Ray, PC and Saxena, A}, title = {The C609T (Pro187Ser) Null Polymorphism of the NQO1 Gene Contributes Significantly to Breast Cancer Susceptibility in North Indian Populations: a Case Control Study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {3}, pages = {1215-1219}, doi = {10.7314/apjcp.2016.17.3.1215}, pmid = {27039751}, issn = {2476-762X}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Genetic Predisposition to Disease ; Genotype ; Humans ; India/epidemiology ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone)/*genetics ; Neoplasm Grading ; Neoplasm Staging ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Risk Factors ; }, abstract = {BACKGROUND: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients.

MATERIALS AND METHODS: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR).

RESULTS: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05).

CONCLUSIONS: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further explored.}, } @article {pmid27037559, year = {2016}, author = {Roncati, L and Barbolini, G and Gatti, AM and Pusiol, T and Piscioli, F and Maiorana, A}, title = {The Uncontrolled Sialylation is Related to Chemoresistant Metastatic Breast Cancer.}, journal = {Pathology oncology research : POR}, volume = {22}, number = {4}, pages = {869-873}, pmid = {27037559}, issn = {1532-2807}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology ; Cell Membrane/metabolism/pathology ; Disease Progression ; Drug Resistance, Neoplasm/*physiology ; Female ; Humans ; Middle Aged ; N-Acetylneuraminic Acid/metabolism ; Prognosis ; Retrospective Studies ; Sialomucins/metabolism ; Sialyltransferases/metabolism ; }, abstract = {Among the scientific communities, there is a convergence of results supporting a direct relationship between dysregulated sialylation and poor prognosis in many human cancers. For this reason, we have retrospectively investigated 169 cases of invasive ductal carcinoma of the breast, coming from female patients aged between 31 and 76 years old. The whole series was subdivided into two prognostic groups: the first group consisted of 138 patients, who showed a post-treatment survival time more than 5 years, while the second group was made up by 31 patients, died within 5 years despite of chemotherapy. All the surgical specimens were fixed in 10 % neutral buffered formalin, paraffin embedded and, then, submitted to routinely haematoxylin/eosin staining and to a further histochemical (Alcian Blue, DDD-Fast Blue B, Mercury Orange), immunohistochemical (ST3GAL5 sialyltransferase, Ki67, c-erbB2, ER, PR) and chemico-elemental characterization. In the 31 cases of breast cancer belonging to the second group, an overexpression of sialomucins and sialyltransferases has been detected. Our results lead us to support that in aggressive chemoresistant breast cancers, the altered expression of sialic acid, due to an uncontrolled sialylation, creates an excessive negative charge on cell membranes, which stimulates repulsion between neoplastic cells and their subsequent access into the blood stream. This event implies an early metastatization and a rapid disease progression with fatal outcome. The early application of Alcian Blue stain on diagnostic biopsies of breast cancer is able to cheaply reveal the sialomucin accumulations, providing for the disease course.}, } @article {pmid27033789, year = {2016}, author = {Li, X and Fu, L and Liu, M and Fu, M}, title = {[Expression of epithelial cell adhesion molecule and molecular subtypes and prognosis of breast cancer].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {41}, number = {3}, pages = {258-263}, doi = {10.11817/j.issn.1672-7347.2016.03.006}, pmid = {27033789}, issn = {1672-7347}, mesh = {*Breast Neoplasms ; Epithelial Cell Adhesion Molecule ; Humans ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; Receptors, Progesterone ; }, abstract = {OBJECTIVE: To investigate clinicopathological and prognostic significance of epithelial cell adhesion molecule (EpCAM) expression in breast cancer and its molecular subtypes.

METHODS: The expression of EpCAM in 835 patients with breast invasive ductal carcinoma was detected by immunohistochemical Max VisionTM method, and its correlation with clinical pathological features and prognosis was analyzed.


RESULTS: The positive expression of EpCAM was related to histological grade, lymph node metastasis, tumor size, clinical stage, the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 (P<0.05). The positive expression rates of EpCAM were 19.2%, 73%, 48.9%, 72.2%, and 62.1%, in Luminal A, Luminal B (HER2-), Luminal B(HER2+), HER2+, and triple-negative subtype, respectively. Log-rank test and univariate COX analysis showed that the EpCAM expression was associated with a poor prognosis in all patients (P<0.001), as well as the triple-negative subtype, luminal B subtype (HER2-), and HER2+ subtype (P<0.05). Multivariate COX analysis showed that EpCAM expression was associated with the survival in patients with the triple-negative or HER2+ subtype (P<0.05).


CONCLUSION: EpCAM may be associated with progress of breast cancer. It is an independent prognostic factor in breast cancer, especially in the triple-negative and HER2+ subtypes.}, } @article {pmid27032401, year = {2016}, author = {Raimo, S and Trojano, L and Siciliano, M and Cuoco, S and D'Iorio, A and Santangelo, F and Abbamonte, L and Grossi, D and Santangelo, G}, title = {Psychometric properties of the Italian version of the multifactorial memory questionnaire for adults and the elderly.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {37}, number = {5}, pages = {681-691}, pmid = {27032401}, issn = {1590-3478}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/*physiology/*psychology ; Cognition/physiology ; Factor Analysis, Statistical ; Female ; Humans ; Italy ; Male ; Memory Disorders/*diagnosis/*psychology ; Mental Status Schedule ; Middle Aged ; *Psychometrics ; Reproducibility of Results ; Self Report ; *Surveys and Questionnaires ; Translating ; }, abstract = {Reliable and valid metamemory measures are needed to assess subjective memory complaints that can be distinct from objective memory performance. The Multifactorial Memory Questionnaire (MMQ) evaluates dimensions of subjective memory functioning such as frequency of memory problems (Ability), affect related to memory abilities (Contentment), and strategy use in everyday life (Strategy). To examine the psychometric properties of the Italian version of the MMQ, six hundred Italian healthy individuals (aged 25-91 years) completed MMQ, a questionnaire assessing metacognition (Cognitive Failures Questionnaire, CFQ) and two batteries assessing cognitive global status (Montreal Cognitive Assessment, MoCA; Mini Mental State Examination, MMSE). MMQ was easy to administer, acceptable, and had good test-retest reliability (r for the total MMQ score 0.95), and internal consistency (Cronbach's α for the total MMQ score = 0.83). An exploratory factor analysis provided a four-factor solution: "Ability" (α = 0.99), "Contentment" (α = 0.91), "External Strategies" (α = 0.85) and "Internal Strategies" (α = 0.78) factors. MMQ total score and MMQ-Ability factor score showed good convergent validity when compared to CFQ score (r rho ≥ 0.51), whereas MMQ total score and the four MMQ factors showed good divergent validity when compared to MoCA and MMSE score (r rho ≤ 0.27). Demographic variables significantly influenced MMQ total score and most subscale scores. From the derived linear equations, we computed correction factors for raw scores and percentile distribution of adjusted scores. The Italian version of MMQ is reliable and valid to assess dimensions of metamemory in adult and elderly subjects.}, } @article {pmid27032379, year = {2016}, author = {Wieczorek, E and Galicki, M and Tomasik, B and Krol, M and Jablonska, E and Fendler, W and Gromadzinska, J and Morawiec, Z and Wasowicz, W and Reszka, E}, title = {Expression of MMP and TIMP mRNA in peripheral blood leukocytes of patients with invasive ductal carcinoma of the breast.}, journal = {The International journal of biological markers}, volume = {31}, number = {3}, pages = {e309-16}, doi = {10.5301/jbm.5000203}, pmid = {27032379}, issn = {1724-6008}, mesh = {Breast Neoplasms/blood/*genetics/metabolism ; Carcinoma, Ductal, Breast/blood/*genetics/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocytes/cytology/*metabolism ; Matrix Metalloproteinases/biosynthesis/*genetics/metabolism ; Middle Aged ; RNA, Messenger/*biosynthesis/blood/genetics ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*genetics/metabolism ; }, abstract = {PURPOSE: An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast.

MATERIALS AND METHODS: Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA.

RESULTS: In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013).

CONCLUSIONS: These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.}, } @article {pmid27028093, year = {2015}, author = {Rutkowski, RE and Salemi, JL and Tanner, JP and Anjohrin, SB and Correia, JA and Watkins, SM and Kirby, RS}, title = {Improving the Completeness of Ascertainment in Florida's Birth Defects Surveillance Program: The Impact of Adding Infant Death and Emergency Department Data.}, journal = {Journal of registry management}, volume = {42}, number = {3}, pages = {91-102}, pmid = {27028093}, issn = {1945-6123}, abstract = {INTRODUCTION: The Florida Birth Defects Registry (FBDR) relies predominantly on a statewide, population-based, passive surveillance system constructed by linking together multiple administrative and clinical databases. With funding limitations and data restrictions a reality in public health, it is imperative for disease registries to have ongoing evaluation of existing and new data sources. This study quantifies the impact of expanding the FBDR case ascertainment net to include infant death certificates (IDCs) and emergency department (ED) discharge data on the reported prevalence of birth defects.

METHODS: Between 2008 and 2011, the FBDR identified cases using various data sources: inpatient and outpatient discharge data (2008-2011), Regional Perinatal Intensive Care Center data (2008), Early Steps program data (2008), IDCs (2009-2011), and ED data (2010-2011). Using hypothetical reconstructions of the FBDR, we examined the overall and unique contribution of each data source in identifying infants with birth defects. This permitted evaluation of a changing FBDR data source mix during the 4-year study period. The effect of adding both IDCs and ED data was investigated by constructing the 2010-2011 FBDR with and without these data sources, and then comparing frequencies and prevalence rates across each scenario. Analyses were conducted for all FBDR cases and for specific birth defect categories; improvements in ascertainment were assessed across sociodemographic and perinatal characteristics.

RESULTS: Overall, IDCs captured 3.4% of all infants with at least 1 birth defect studied, ED data captured 3.9% of the cases, and together the 2 data sources captured 7.2%. However, IDCs uniquely identified 0.8% of all cases, ED data uniquely identified 0.7% of all cases, and collectively they identified only 1.4% of cases that would otherwise have been missed. The unique contribution of IDC and ED data to case identification varied by defect and across sociodemographic and perinatal subgroups, with the largest impact among infants with anencephalus (64.7%), trisomy 13 (52.0%), trisomy 18 (22.2%), and encephalocele (13.3%), or those who were born weighing less than 1,500 grams or less than 32 weeks' gestation, or whose mothers' education was eighth grade or less.

DISCUSSION: Although their unique contribution is small when all defects are considered together, IDCs and ED data contribute cases that would otherwise have been disproportionately lost and are thus an important addition to surveillance activities. The FBDR continues to strive to create a comprehensive, accurate, and efficient statewide birth defects surveillance system.}, } @article {pmid27022189, year = {2016}, author = {Lau, SS and Cheung, PS and Wong, TT and Ma, MK and Kwan, WH}, title = {Comparison of clinical and pathological characteristics between screen-detected and self-detected breast cancers: a Hong Kong study.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {22}, number = {3}, pages = {202-209}, doi = {10.12809/hkmj154575}, pmid = {27022189}, issn = {1024-2708}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/therapy ; *Breast Self-Examination ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*pathology/therapy ; Early Detection of Cancer/statistics & numerical data ; Female ; Hong Kong ; Humans ; Logistic Models ; Lymph Nodes/pathology ; Mammography ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the leading cause of death of Hong Kong women with increasing incidence. This study aimed to determine any prognostic differences between screen-detected and self-detected cases of breast cancer in a cohort of Hong Kong patients.

METHODS: This was a case series with internal comparison carried out in a private hospital in Hong Kong. Approximately 3000 cases of Chinese patients diagnosed with ductal carcinoma in situ or invasive breast cancer were reviewed.

RESULTS: The screen-detected group showed better pathological characteristics than the self-detected group. Number of lymph nodes involved, invasive tumour size, and tumour grade were more favourable in the screen-detected group. There was also a lower proportion of patients with pure invasive ductal carcinoma and mastectomy in the screen-detected group.

CONCLUSION: This study provides indirect evidence that women in the local population may gain clinical benefit from regular breast cancer screening. The findings need to be validated in a representative population of Hong Kong women.}, } @article {pmid27020659, year = {2016}, author = {Crottès, D and Félix, R and Meley, D and Chadet, S and Herr, F and Audiger, C and Soriani, O and Vandier, C and Roger, S and Angoulvant, D and Velge-Roussel, F}, title = {Immature human dendritic cells enhance their migration through KCa3.1 channel activation.}, journal = {Cell calcium}, volume = {59}, number = {4}, pages = {198-207}, doi = {10.1016/j.ceca.2016.02.008}, pmid = {27020659}, issn = {1532-1991}, mesh = {Calcium/*metabolism ; *Cell Movement/drug effects ; Dendritic Cells/*cytology/drug effects/*metabolism ; Humans ; Intermediate-Conductance Calcium-Activated Potassium Channels/*metabolism ; Intracellular Space/drug effects/metabolism ; Pyrazoles/pharmacology ; }, abstract = {Migration capacity is essential for dendritic cells (DCs) to present antigen to T cells for the induction of immune response. The DC migration is supposed to be a calcium-dependent process, while not fully understood. Here, we report a role of the KCa3.1/IK1/SK4 channels in the migration capacity of both immature (iDC) and mature (mDC) human CD14(+)-derived DCs. KCa3.1 channels were shown to control the membrane potential of human DC and the Ca(2+) entry, which is directly related to migration capacities. The expression of migration marker such as CCR5 and CCR7 was modified in both types of DCs by TRAM-34 (100nM). But, only the migration of iDC was decreased by use of both TRAM-34 and KCa3.1 siRNA. Confocal analyses showed a close localization of CCR5 with KCa3.1 in the steady state of iDC. Finally, the implication of KCa3.1 seems to be limited to the migration capacities as T cell activation of DCs appeared unchanged. Altogether, these results demonstrated that KCa3.1 channels have a pro-migratory effect on iDC migration. Our findings suggest that KCa3.1 in human iDC play a major role in their migration and constitute an attractive target for the cell therapy optimization.}, } @article {pmid27015895, year = {2016}, author = {Adachi, Y and Ishiguro, J and Kotani, H and Hisada, T and Ichikawa, M and Gondo, N and Yoshimura, A and Kondo, N and Hattori, M and Sawaki, M and Fujita, T and Kikumori, T and Yatabe, Y and Kodera, Y and Iwata, H}, title = {Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma.}, journal = {BMC cancer}, volume = {16}, number = {}, pages = {248}, pmid = {27015895}, issn = {1471-2407}, mesh = {Aged ; Breast Neoplasms/classification/drug therapy/epidemiology/*pathology ; Carcinoma, Ductal, Breast/classification/drug therapy/epidemiology/*pathology ; Carcinoma, Lobular/classification/drug therapy/epidemiology/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/classification/drug therapy/epidemiology/*pathology ; Neoplasm Staging ; Prognosis ; Treatment Outcome ; }, abstract = {BACKGROUND: The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC.

METHODS: Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC.

RESULTS: The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9% and 88.4% for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6% and 93.1% for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered.

CONCLUSIONS: Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC.}, } @article {pmid27014949, year = {2016}, author = {Cenarro, A and Etxebarria, A and de Castro-Orós, I and Stef, M and Bea, AM and Palacios, L and Mateo-Gallego, R and Benito-Vicente, A and Ostolaza, H and Tejedor, T and Martín, C and Civeira, F}, title = {The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {101}, number = {5}, pages = {2113-2121}, doi = {10.1210/jc.2015-3874}, pmid = {27014949}, issn = {1945-7197}, mesh = {Adult ; Apolipoproteins E/*genetics/metabolism ; Case-Control Studies ; DNA Mutational Analysis ; Down-Regulation/*genetics ; Female ; Hepatocytes/*metabolism ; Humans ; Hyperlipoproteinemia Type II/*genetics/metabolism ; Male ; Middle Aged ; *Mutation ; Receptors, LDL/*genetics/metabolism ; }, abstract = {CONTEXT: The p.Leu167del mutation in the APOE gene has been associated with hyperlipidemia.

OBJECTIVES: Our objective was to determine the frequency of p.Leu167del mutation in APOE gene in subjects with autosomal dominant hypercholesterolemia (ADH) in whom LDLR, APOB, and PCSK9 mutations had been excluded and to identify the mechanisms by which this mutant apo E causes hypercholesterolemia.

DESIGN: The APOE gene was analyzed in a case-control study.

SETTING: The study was conducted at a University Hospital Lipid Clinic.

Two groups (ADH, 288 patients; control, 220 normolipidemic subjects) were included.

INTERVENTION: We performed sequencing of APOE gene and proteomic and cellular experiments.

MAIN OUTCOME MEASURE: To determine the frequency of the p.Leu167del mutation and the mechanism by which it causes hypercholesterolemia.

RESULTS: In the ADH group, nine subjects (3.1%) were carriers of the APOE c.500_502delTCC, p.Leu167del mutation, cosegregating with hypercholesterolemia in studied families. Proteomic quantification of wild-type and mutant apo E in very low-density lipoprotein (VLDL) from carrier subjects revealed that apo E3 is almost a 5-fold increase compared to mutant apo E. Cultured cell studies revealed that VLDL from mutation carriers had a significantly higher uptake by HepG2 and THP-1 cells compared to VLDL from subjects with E3/E3 or E2/E2 genotypes. Transcriptional down-regulation of LDLR was also confirmed.

CONCLUSIONS: p.Leu167del mutation in APOE gene is the cause of hypercholesterolemia in the 3.1% of our ADH subjects without LDLR, APOB, and PCSK9 mutations. The mechanism by which this mutation is associated to ADH is that VLDL carrying the mutant apo E produces LDLR down-regulation, thereby raising plasma low-density lipoprotein cholesterol levels.}, } @article {pmid27011515, year = {2015}, author = {Challa, VR and Deshmane, V}, title = {Challenges in Diagnosis and Management of Paget's Disease of the Breast-a Retrospective Study.}, journal = {The Indian journal of surgery}, volume = {77}, number = {Suppl 3}, pages = {1083-1087}, pmid = {27011515}, issn = {0972-2068}, abstract = {Paget's disease of the breast is uncommon and patients may present with nipple discharge, eczema, plaque or nipple destruction with or without a lump. The aim of the present study was to evaluate the presentation, clinicopathological features and treatment given for patients presenting with Paget's disease of the breast. We performed a retrospective analysis of medical records of patients who were treated at our centre for Paget's disease of the breast from 2006-2011. Twenty patients were treated in this period. Twelve patients had associated lump and eight patients did not have a lump in the breast. Two patients did not have a lump or any detected abnormality in mammography. Multicentricity was present in five patients. Diagnosis of malignancy was made by fine-needle aspiration cytology for patients with palpable lump and nipple wedge biopsy for patients with no lump. Modified radical mastectomy was done in 10 patients: 2 patients underwent total mastectomy and sentinel lymph node biopsy and 8 patients underwent central quadrantectomy and sentinel lymph node biopsy. Eleven patients had invasive ductal carcinoma, one patient had ductal carcinoma in situ with foci of invasion and eight patients had ductal carcinoma in situ. Seven patients had lymph node metastases. Three patients had recurrence, one had local recurrence and two had distant recurrences. The mean follow up period was 28 months (range 15-64 months). Paget's disease of the breast is a rare entity and one needs imaging and biopsy to diagnose these patients as they have associated cancer. They can be considered for breast conservation surgery with good cosmetic and oncological results.}, } @article {pmid27009810, year = {2016}, author = {Wang, XX and Jiang, YZ and Liu, XY and Li, JJ and Song, CG and Shao, ZM}, title = {Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database.}, journal = {Oncotarget}, volume = {7}, number = {16}, pages = {22665-22673}, pmid = {27009810}, issn = {1949-2553}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Carcinoma, Medullary/*mortality/pathology ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Proportional Hazards Models ; SEER Program ; Young Adult ; }, abstract = {Medullary breast carcinoma (MBC) is a unique histological subtype of breast cancer. Our study was designed to identify difference in characteristics and outcomes between MBC and invasive ductal carcinoma (IDC), and further confirm the prognostic factors of MBC. Utilizing Surveillance, Epidemiology, and End Results (SEER), we identified 84,764 eligible patients, including 309 MBC and 84,455 IDC. Compared with the IDC group, the MBC group was associated with younger age at diagnosis, higher grade, more advanced stage, larger tumor size, and higher proportion of triple-negative breast cancer (TNBC). Kaplan-Meier analysis and univariate Cox proportional hazard regression model showed that patients with IDC had significantly better breast cancer-specific survival (BCSS) compared to MBC, but they had similar overall survival (OS). However, MBC histology was no longer a surrogate for worse BCSS or OS after 1:1 matching by age, American Joint Committee on Cancer (AJCC) stage, grade and breast subtype. In addition, it was exposed that not married status, high grade, large tumor size, positive nodal status, the subtype of TNBC and no receipt of radiation therapy were significantly associated with poor BCSS and OS. In conclusion, MBC demonstrated more aggressive behavior but similar outcomes compared to IDC, which may be determined by prognostic factors such as breast subtype. These results not only confer deeper insight into MBC but contribute to individualized and tailored therapy, and thereby may improve clinical management and outcomes.}, } @article {pmid27007655, year = {2016}, author = {Jin, B and Wu, BW and Wen, ZC and Shi, HM and Zhu, J}, title = {HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {49}, number = {4}, pages = {e5131}, pmid = {27007655}, issn = {1414-431X}, mesh = {Biopsy ; Cardiomyopathy, Dilated/*genetics/pathology ; Case-Control Studies ; Genetic Predisposition to Disease ; HLA-DR3 Antigen/*genetics ; Humans ; Myocardium/pathology ; Polymorphism, Genetic ; Risk Factors ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC.}, } @article {pmid27003606, year = {2016}, author = {Kamranpour, NO and Miri, AK and James-Bhasin, M and Nazhat, SN}, title = {A gel aspiration-ejection system for the controlled production and delivery of injectable dense collagen scaffolds.}, journal = {Biofabrication}, volume = {8}, number = {1}, pages = {015018}, doi = {10.1088/1758-5090/8/1/015018}, pmid = {27003606}, issn = {1758-5090}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Cells, Cultured ; Collagen/*administration & dosage/chemistry ; Compressive Strength ; Elastic Modulus ; Equipment Design ; Equipment Failure Analysis ; Hydrogels/*administration & dosage/chemistry ; Injections/*instrumentation ; Mesenchymal Stem Cell Transplantation/*instrumentation ; Mice ; Mice, Inbred C57BL ; Prosthesis Implantation/instrumentation ; Suction/*instrumentation ; Tensile Strength ; *Tissue Scaffolds ; Viscosity ; }, abstract = {A gel aspiration-ejection (GAE) system has been developed for the advanced production and delivery of injectable dense collagen (I-DC) gels of unique collagen fibrillar densities (CFDs). Through the creation of negative pressure, GAE aspirates prefabricated highly hydrated collagen gels into a needle, simultaneously inducing compaction and meso-scale anisotropy (i.e., fibrillar alignment) on the gels, and by subsequent reversal of the pressure, I-DC gels can be controllably ejected. The system generates I-DC gels with CFDs ranging from 5 to 32 wt%, controlling the initial scaffold microstructure, anisotropy, hydraulic permeability, and mechanical properties. These features could potentially enable the minimally invasive delivery of more stable hydrogels. The viability, metabolic activity, and differentiation of seeded mesenchymal stem cells (MSCs) was investigated in the I-DC gels of distinct CFDs and extents of anisotropy produced through two different gauge needles. MSC osteoblastic differentiation was found to be relatively accelerated in I-DC gels that combined physiologically relevant CFDs and increased fibrillar alignment. The ability to not only support homogenous cell seeding, but also to direct and accelerate their differentiation through tissue-equivalent anisotropy, creates numerous opportunities in regenerative medicine.}, } @article {pmid26994487, year = {2016}, author = {Sanguinetti, A and Polistena, A and Lucchini, R and Monacelli, M and Galasse, S and Avenia, S and Triola, R and Bugiantella, W and Cirocchi, R and Rondelli, F and Avenia, N}, title = {Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit.}, journal = {International journal of surgery case reports}, volume = {20S}, number = {Suppl}, pages = {8-11}, pmid = {26994487}, issn = {2210-2612}, abstract = {BACKGROUND: The male breast cancer (MBC) is a rare and represents less than 1% of all malignancies in men and only 1% of all breast cancers incident. We illustrate the experience of our team about the clinico-pathological characteristics, treatment and prognostic factors of patients treated over a period of twenty years .

RESULTS: Forty-seven patients were collected 1995-2014 at the Breast Unit of the Hospital of Terni, Italy. The average age was 67 years and the median time to diagnosis from the onset of symptoms was 16 months. The main clinical complaint was sub areolar swelling in 36, 76% of cases. Most patients have come to our attention with advanced disease. The histology of about ninety percent of the tumors were invasive ductal carcinoma. Management consisted mainly of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The median follow-up was 38 months. The evolution has been characterized by local recurrences; in eight cases (17% of all patients). Metastasis occurred in 15 cases (32% of all patients). The site of bone metastases was in eight cases; lung in four cases; liver in three cases; liver and skin in one case and pleura and skin in one case.

CONCLUSION: The male breast cancer has many similarities to breast cancer in women, but there are distinct functions that need to be appreciated. Future research for a better understanding of the disease should provide a better account of genetic and epigenetic characteristics of these forms; but, above all, epidemiological and biological cohorts numerically more consistent.}, } @article {pmid26989770, year = {2016}, author = {Kricheli-Katz, T and Regev, T}, title = {How many cents on the dollar? Women and men in product markets.}, journal = {Science advances}, volume = {2}, number = {2}, pages = {e1500599}, doi = {10.1126/sciadv.1500599}, pmid = {26989770}, issn = {2375-2548}, mesh = {Adult ; Female ; Humans ; Male ; Marketing/*economics ; Sexism/*economics ; United States ; }, abstract = {Gender inequality in contemporary U.S. society is a well-documented, widespread phenomenon. However, little is known about gender disparities in product markets. This study is the first to use actual market data to study the behavior of women and men as sellers and buyers and differences in market outcomes. We analyze a unique and large data set containing all eBay auction transactions of most popular products by private sellers between the years 2009 and 2012. Women sellers received a smaller number of bids and lower final prices than did equally qualified men sellers of the exact same product. On average, women sellers received about 80 cents for every dollar a man received when selling the identical new product and 97 cents when selling the same used product. These findings held even after controlling for the sentiments that appear in the text of the sellers' listings. Nonetheless, it is worth noting that this gap varied by the type of the product being sold. As a policy, eBay does not reveal the gender of users. We attribute the price differences to the ability of buyers to discern the gender of the seller. We present results from an experiment that shows that people accurately identify the gender of sellers on the basis of typical information provided in postings. We supplement the analysis with an additional off-eBay experiment showing that, in a controlled setting, people are willing to pay less for money-value gift cards when they are sold by women rather than men.}, } @article {pmid26989359, year = {2015}, author = {Yari, K and Rahimi, Z and Payandeh, M and Rahimi, Z}, title = {MMP-7 A-181G Polymorphism in Breast Cancer Patients from Western Iran.}, journal = {Breast care (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {398-402}, pmid = {26989359}, issn = {1661-3791}, abstract = {BACKGROUND: Matrix metalloproteinases (MMPs) are upregulated in tumors. The MMP-7 A-181G polymorphism is associated with increased expression of the MMP-7 gene. Aim of the present study was to investigate the association between the MMP-7 A-181G polymorphism and susceptibility to breast cancer.

PATIENTS AND METHODS: The MMP-7 A-181G variants were studied in a cohort of 251 subjects consisting of 100 breast cancer patients and 151 healthy controls; all were from Western Iran. The MMP-7 A-181G genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

RESULTS: The frequencies of the MMP-7 AA, AG, and GG genotypes in healthy individuals were 34.4, 50.4, and 15.2%, respectively. In breast cancer patients, the frequencies of AA (34%), AG (52%), and GG (14%) genotypes (p = 0.95) were similar to those in the controls. There was a trend toward an increased frequency of the combined genotype of MMP-7 AG+GG in patients with lymph node metastasis (70.4%) compared to those without metastasis (66.7%). Also, in patients with invasive lobular carcinoma, the frequency of the MMP-7 AG+GG genotype tended to be higher (71.4%) compared to that in patients with invasive ductal carcinoma (66.2%) (p = 0.78).

CONCLUSION: Our findings indicate that the MMP-7 A-181G polymorphism may not be correlated with susceptibility to breast cancer in our population.}, } @article {pmid26981296, year = {2016}, author = {Okuda, T and Yamamoto, S and Matsuo, S and Kataoka, H and Kitawaki, J}, title = {Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer) to the Brain, Diagnosed at 18 Weeks' Gestation: A Case Report and Review of the Literature.}, journal = {Case reports in obstetrics and gynecology}, volume = {2016}, number = {}, pages = {9813253}, pmid = {26981296}, issn = {2090-6684}, abstract = {We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC). A 35-year-old woman (gravida 2, para 0-1-0-1) underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]). The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks' gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks' gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.}, } @article {pmid26980443, year = {2016}, author = {Fujikawa, Y and Roma, LP and Sobotta, MC and Rose, AJ and Diaz, MB and Locatelli, G and Breckwoldt, MO and Misgeld, T and Kerschensteiner, M and Herzig, S and Müller-Decker, K and Dick, TP}, title = {Mouse redox histology using genetically encoded probes.}, journal = {Science signaling}, volume = {9}, number = {419}, pages = {rs1}, doi = {10.1126/scisignal.aad3895}, pmid = {26980443}, issn = {1937-9145}, mesh = {Animals ; HEK293 Cells ; Humans ; Mice ; Mice, Nude ; Molecular Imaging/*methods ; Molecular Probes/genetics/*metabolism ; Oxidation-Reduction ; *Transgenes ; }, abstract = {Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.}, } @article {pmid26978126, year = {2016}, author = {Accurso, A and Ciancia, G and Della Corte, GA and Reale, P and Accardo, G and Salerno, C and Bordoni, D and Falco, G and Rocco, N}, title = {A rare case of true carcinosarcoma of the breast.}, journal = {International journal of surgery case reports}, volume = {21}, number = {}, pages = {125-128}, pmid = {26978126}, issn = {2210-2612}, abstract = {BACKGROUND: True carcinosarcoma of the breast is an extremely rare condition, accounting for 0.08-0.2% of all breast malignancies. The correct definition of this tumor requires both a carcinomatous component and a malignant non-epithelial component of mesenchymal origin, without evidence of a transition zone between the two elements.

CASE PRESENTATION: We present a case of a 49-year-old woman presenting with a 4cm mass at the level of her left breast upper-outer quadrant with a histologic diagnosis of true carcinosarcoma of the breast.

DISCUSSION: The most appropriate therapeutic regimens for breast carcinosarcoma are still unclear because of the rarity of this condition, but Breast Conserving Treatment (BCT) followed by adjuvant chemotherapy seems to provide a prognosis equalling that of usual Invasive Ductal Carcinoma of the breast.}, } @article {pmid26975010, year = {2016}, author = {Dong, A and Wang, Y and Lu, J and Zuo, C}, title = {Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {7}, pages = {543-557}, pmid = {26975010}, issn = {1536-0229}, mesh = {Breast/metabolism ; Breast Diseases/*diagnostic imaging/metabolism ; Breast Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Male ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals/*pharmacokinetics ; }, abstract = {Interpretation of F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging.}, } @article {pmid26972027, year = {2016}, author = {Mata-Cantero, L and Azkargorta, M and Aillet, F and Xolalpa, W and LaFuente, MJ and Elortza, F and Carvalho, AS and Martin-Plaza, J and Matthiesen, R and Rodriguez, MS}, title = {New insights into host-parasite ubiquitin proteome dynamics in P. falciparum infected red blood cells using a TUBEs-MS approach.}, journal = {Journal of proteomics}, volume = {139}, number = {}, pages = {45-59}, doi = {10.1016/j.jprot.2016.03.004}, pmid = {26972027}, issn = {1876-7737}, mesh = {*Erythrocytes/metabolism/parasitology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/*metabolism ; Plasmodium falciparum/*physiology ; Proteome/*metabolism ; Protozoan Proteins/*metabolism ; Ubiquitin/*metabolism ; }, abstract = {UNLABELLED: Malaria, caused by Plasmodium falciparum (P. falciparum), ranks as one of the most baleful infectious diseases worldwide. New antimalarial treatments are needed to face existing or emerging drug resistant strains. Protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum. Inhibition of the ubiquitin proteasome system (UPS), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication. P. falciparum and erythrocyte UPS coexist during IDC but the nature of their relationship is largely unknown. We used an approach based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis followed by mass spectrometry to identify major components of the TUBEs-associated ubiquitin proteome of both host and parasite during ring, trophozoite and schizont stages. Ring-exported protein (REX1), a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, was found to reach a maximum level of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs associated ubiquitin proteome decreased during the infection, whereas the equivalent P. falciparum TUBEs-associated ubiquitin proteome counterpart increased. Major cellular processes such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection.

BIOLOGICAL SIGNIFICANCE: In this work we analyze for the first time the interconnection between Plasmodium and human red blood cells ubiquitin-regulated proteins in the context of infection. We identified a number of human and Plasmodium proteins whose ubiquitylation pattern changes during the asexual infective stage. We demonstrate that ubiquitylation of REX1, a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, peaks in trophozoites stage. The ubiquitin-proteome from P. falciparum infected red blood cells (iRBCs) revealed a significant host-parasite crosstalk, underlining the importance of ubiquitin-regulated proteolytic activities during the intraerythrocytic developmental cycle (IDC) of P. falciparum. Major cellular processes defined from gene ontology such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection. Given the importance of ubiquitylation in the development of infectious diseases, this work provides a number of potential drug-target candidates that should be further explored.}, } @article {pmid26971121, year = {2016}, author = {Sun, H and Li, K and Shen, S}, title = {A study of the role of Notch1 and JAG1 gene methylation in development of breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {33}, number = {4}, pages = {35}, pmid = {26971121}, issn = {1559-131X}, mesh = {Adolescent ; Adult ; Aged ; Breast Diseases/genetics/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; CpG Islands ; DNA Methylation ; Female ; Humans ; Hyperplasia/pathology ; Jagged-1 Protein/*genetics/metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Receptor, Notch1/*genetics/metabolism ; Young Adult ; }, abstract = {This study is to explore the roles of gene methylation of Notch1 and JAG1 in development of invasive ductal carcinoma of breast. Quantitative analysis the DNA methylation levels of Notch1 and JAG1 gene by the MassARRAY method in invasive ductal carcinoma of breast (IDC; n = 89), atypical ductal hyperplasia of breast (ADH; n = 11), and ordinary ductal hyperplasia of breast (UDH; n = 20). The expressions of JAG1 and Notch1 protein in four breast tissues were detected by immunohistochemistry SP method. (1) Positive expression rates of Notch1 protein in IDC and DCIS were 88.7 % (79/89) and 70.0 % (14/20), respectively, which were significantly higher than the levels in ADH (36.0 %, 4/11) and UDH (25.0 %, 5/20; P < 0.05). Notch1 protein expression was significant positively correlated with lymph node metastasis, pathological grades, and TNM stages of IDC. (2) Positive expression rates of JAG1 protein in IDC and DCIS were 89.9 % (80/89) and 75.0 % (15/20), respectively, which were significantly higher than those of ADH (45.0 %, 5/11) and UDH (30.0 %, 6/20; P < 0.05). JAG1 protein expression was significant positive correlation with lymph node metastasis, pathological grades and TNM stages of IDC. There is an overall hypomethylation alteration of Notch1 and JAG gene in IDC, with corresponding over-expression of Notch1 and JAG1 protein. This inverse correlation shows that the alteration of protein expression results from hypomethylation oncogene Notch1 and JAG1, and this change may play an important role in occurrence and progression of breast cancer.}, } @article {pmid26971129, year = {2016}, author = {Saha, M and Arun, I and Basak, B and Agarwal, S and Ahmed, R and Chatterjee, S and Bhargava, R and Chakraborty, C}, title = {Quantitative microscopic evaluation of mucin areas and its percentage in mucinous carcinoma of the breast using tissue histological images.}, journal = {Tissue & cell}, volume = {48}, number = {3}, pages = {265-273}, doi = {10.1016/j.tice.2016.02.005}, pmid = {26971129}, issn = {1532-3072}, mesh = {Adenocarcinoma, Mucinous/*diagnostic imaging/metabolism/pathology ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Mucins/*biosynthesis ; Neoplasm Grading ; }, abstract = {Mucinous carcinoma (MC) of the breast is very rare (∼1-7% of all breast cancers), invasive ductal carcinoma. Presence of pools of extracellular mucin is one of the most important histological features for MC. This paper aims at developing a quantitative computer-aided methodology for automated identification of mucin areas and its percentage using tissue histological images. The proposed method includes pre-processing (i.e., colour space transformation and colour normalization), mucin regions segmentation, post-processing, and performance evaluation. The proposed algorithm achieved 97.74% segmentation accuracy in comparison to ground truths. In addition, the percentage of mucin present in the tissue regions is calculated by the mucin index (MI) for grading MC (pure, moderately, minimally mucinous).}, } @article {pmid26963620, year = {2016}, author = {Gonzalez-Sistal, A and Baltasar-Sánchez, A and Menéndez, P and Arias, JI and Ruibal, Á}, title = {Breastfeeding and Immunohistochemical Expression of ki-67, p53 and BCL2 in Infiltrating Lobular Breast Carcinoma.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151093}, pmid = {26963620}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*pathology ; *Breast Feeding ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Female ; Humans ; Ki-67 Antigen/*analysis ; Middle Aged ; Neoplasm Invasiveness/pathology ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {BACKGROUND/AIM: Invasive lobular breast carcinoma is the second most common type of breast cancer after invasive ductal carcinoma. According to the American Cancer Society, more than 180,000 women in the United States find out they have invasive breast cancer each year. Personal history of breast cancer and certain changes in the breast are correlated with an increased breast cancer risk. The aim of this work was to analyze breastfeeding in patients with infiltrating lobular breast carcinoma, in relation with: 1) clinicopathological parameters, 2) hormonal receptors and 3) tissue-based tumor markers.

MATERIALS AND METHODS: The study included 80 women with ILC, 46 of which had breastfeed their children. Analyzed parameters were: age, tumor size, axillary lymph node (N), distant metastasis (M), histological grade (HG), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Ki-67, p53 and BCL2.

RESULTS: ILC of non-lactating women showed a larger (p = 0.009), lymph node involvement (p = 0.051) and distant metastasis (p = 0.060). They were also more proliferative tumors measured by Ki-67 (p = 0.053). Breastfeeding history did not influence the subsequent behavior of the tumor regardless of histological subtype.

CONCLUSION: Lactation seems to influence the biological characteristics of ILC defining a subgroup with more tumor size, axillary lymph node involvement, distant metastasis and higher proliferation measured by ki-67 expression.}, } @article {pmid26960462, year = {2015}, author = {Göksu, SS and Bozcuk, H and Koral, L and Çakar, B and Gündüz, S and Tatlı, AM and Arslan, D and Uysal, M and Koçer, M and Artaç, M and Karabulut, B and Coşkun, HS and Özdoğan, M and Savaş, B}, title = {Factors predicting lapatinib efficacy in HER-2+ metastatic breast carcinoma: Does it work better in different histologic subtypes?.}, journal = {Indian journal of cancer}, volume = {52}, number = {4}, pages = {517-519}, doi = {10.4103/0019-509X.178382}, pmid = {26960462}, issn = {1998-4774}, mesh = {Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/enzymology/pathology ; Disease-Free Survival ; Female ; Humans ; Lapatinib ; Middle Aged ; Neoplasm Metastasis ; Predictive Value of Tests ; Prognosis ; Quinazolines/*therapeutic use ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {CONTEXT: Introduction of trastuzumab, a recombinant monoclonal antibody against the extracellular domain of HER-2, is a cornerstone in the treatment of HER-2+ breast carcinoma. However, many cancers that have an initial response to trastuzumab will progress some time later. After progression on trastuzumab-based first-line treatment, there are several options. Although TDM-1 (Trastuzumab emtansine) has prolonged progression-free survival (PFS) and overall survival in patients previously treated with trastuzumab and taxane, it is still not available in Turkey. Patients may be switched to lapatinib (an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2), or they may re-challenge with trastuzumab. There is no clear definition of the patients who should be switched to lapatinib.

AIM: In this study, we investigated the factors predicting the efficacy of lapatinib.

SUBJECTS AND METHODS: Totally, 94 patients treated with lapatinib for metastatic breast carcinoma was included in our study. Retrospective data including pathology, treatments and treatment results, metastatic sites, and laboratory tests were collected.

RESULTS: Progression-free survival was 9.1 months. Histologic subtypes other than invasive ductal carcinoma and liver metastasis were inversely related with PFS. Overall survival was 22.1 months, and patients with histologic subtypes other than invasive ductal carcinoma and who progress with brain metastasis had a worse prognosis.

CONCLUSION: Clinicians should give attention to histologic subtype and metastatic sites when choosing patients for lapatinib treatment.}, } @article {pmid26955804, year = {2016}, author = {Jin, H and Ji, M and Chen, L and Liu, Q and Che, S and Xu, M and Lin, Z}, title = {The clinicopathological significance of Mortalin overexpression in invasive ductal carcinoma of breast.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {35}, number = {}, pages = {42}, pmid = {26955804}, issn = {1756-9966}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Cell Line, Tumor ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Middle Aged ; Mitochondrial Proteins/*metabolism ; Prognosis ; Survival Analysis ; Up-Regulation ; }, abstract = {BACKGROUND: Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. This study aims to investigate the Mortalin expression in breast cancer and its correlation with the outcome of the patients with breast cancer.

METHODS: A total of 155 invasive ductal carcinoma of breast patients with strict follow-up, 52 ductal carcinoma in situ (DCIS) and 45 adjacent non-tumor breast tissues were selected for immunohistochemical (IHC) staining of Mortalin protein. The localization of Mortalin protein was detected in MDA-MB231 breast cancer cells using immunofluorescence (IF) staining. The correlations between overexpression of Mortalin and the clinical features of patients with breast cancer were evaluated using chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models.

RESULTS: Mortalin protein showed a mainly cytoplasmic staining pattern in breast cancers by using IHC staining in paraffin embedded breast cancer tissues and IF staining in MDA-MB231 breast cancer cells. The strongly positive rate of Mortalin protein was 63.9% (99/155) in invasive ductal carcinoma of breast and was significantly higher than in DCIS 34.6% (18/52) and adjacent non-tumor tissues 15.6% (7/45). Overexpression of Mortalin was closely correlated with histological grade, clinical stage, lymph node metastasis, lower disease free survival (DFS) and overall survival (OS) rates of patients with breast cancer. Moreover, multivariate analysis suggested that Mortalin emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.

CONCLUSIONS: Mortalin is upregulated in breast cancer, and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.}, } @article {pmid26950599, year = {2016}, author = {Stephen, HM and Khoury, RJ and Majmudar, PR and Blaylock, T and Hawkins, K and Salama, MS and Scott, MD and Cosminsky, B and Utreja, NK and Britt, J and Conway, RE}, title = {Epigenetic suppression of neprilysin regulates breast cancer invasion.}, journal = {Oncogenesis}, volume = {5}, number = {3}, pages = {e207}, pmid = {26950599}, issn = {2157-9024}, abstract = {In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer, and epigenetic suppression of neprilysin in invasive breast cancer cells enables invasion. Together, this implicates neprilysin as an important regulator of breast cancer invasion and clarifies its utility as a potential biomarker for invasive breast cancer.}, } @article {pmid26948247, year = {2016}, author = {Mann, JM and Osian, AD and Brandmaier, A and Yan, W and Sung, KJ and Siegel, B and Fink, S and Kaplan, B and Fulman, M and Wu, G and Christos, P and Nori, D and Ravi, A}, title = {Excellent Long-term Breast Preservation Rate After Accelerated Partial Breast Irradiation Using a Balloon Device.}, journal = {Clinical breast cancer}, volume = {16}, number = {3}, pages = {217-222}, doi = {10.1016/j.clbc.2016.02.010}, pmid = {26948247}, issn = {1938-0666}, mesh = {Aged ; Aged, 80 and over ; Brachytherapy/instrumentation/*methods ; Breast Neoplasms/*radiotherapy ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Accelerated partial breast irradiation (APBI) using a balloon device has been well tolerated. A recent retrospective population-based study showed an increase in the rate of subsequent mastectomy for patients who undergo APBI compared with whole breast radiation therapy. Our aim was to analyze the long-term results of patients treated with APBI at our institution to determine the salvage mastectomy and locoregional recurrence rates and cosmesis outcomes.

MATERIALS AND METHODS: After institutional review board approval, we conducted a retrospective review of 111 patients treated from June 2003 to October 2014 at our institution for early-stage breast cancer using a balloon device. After lumpectomy and nodal staging, the patients underwent APBI with high-dose rate iridium-192 brachytherapy. A computed tomography-based 3-dimensional plan was created, and a dose of 34 Gy in 10 fractions was given twice daily, 6 hours apart, over 5 days. Follow-up examinations were performed 2 to 3 times annually by either a surgeon and/or a radiation oncologist. Annual mammograms were obtained. The patients included postmenopausal women with node-negative early-stage invasive ductal carcinoma with a tumor size < 3 cm (n = 93) or ductal carcinoma in situ (n = 18). Cosmesis was evaluated using the Harvard criteria, as excellent, good, fair, or poor.

RESULTS: At a median follow-up period of 66 months (range, 1-139 months) after completing treatment, with a minimum of 5 years of follow-up data for 62 patients (55.9%), the incidence of ipsilateral breast tumor recurrence (IBTR) was 2.7% (n = 3) and the incidence of ipsilateral axilla nodal recurrence was 1.8% (n = 2). The ipsilateral breast preservation rate was 97.3%. The salvage mastectomy rate was 2.7% (n = 3), and the 5-year salvage mastectomy-free rate was 98.7% (95% confidence interval, 91.0%-99.8%). No distant failure developed, and no breast cancer-related deaths occurred. The 5-year overall survival rate was 91.7% (95% confidence interval, 83.2%-96.0%), and the 10-year breast cancer-specific survival rate was 100%. Of the 3 cases of IBTR, 2 were estrogen receptor negative (P = .076). The mean interval to IBTR was 78.7 ± 27.5 months from treatment completion. A significant association was noted between African-American ethnicity and IBTR (P = .0398). Excellent to good cosmesis was observed in 98.1% of the patients. The maximum skin dose (mean value) for patients with excellent, good, and fair cosmesis was 302.2 Gy, 315.4 Gy, and 372.5 Gy (88.9%, 92.7%, and 109.5% of the prescription dose), respectively. The maximum skin dose was < 340 Gy (100% of the prescribed dose) in 69.9% of patients with excellent to good cosmesis.

CONCLUSION: The long-term follow-up data of patients receiving APBI with a balloon device showed a low salvage mastectomy rate with durable long-term breast preservation. Excellent local control with good cosmesis was noted in these postmenopausal patients treated with APBI.}, } @article {pmid26943990, year = {2016}, author = {Stecklein, SR and Shen, X and Mitchell, MP}, title = {Post-Mastectomy Radiation Therapy for Invasive Lobular Carcinoma: A Comparative Utilization and Outcomes Study.}, journal = {Clinical breast cancer}, volume = {16}, number = {4}, pages = {319-326}, doi = {10.1016/j.clbc.2016.02.001}, pmid = {26943990}, issn = {1938-0666}, mesh = {Aged ; Breast Neoplasms/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Lobular/*mortality/pathology/*radiotherapy/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Radiotherapy, Adjuvant/statistics & numerical data ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: To date, there have been no analyses to assess factors that influence post-mastectomy radiation therapy (PMRT) utilization in invasive lobular carcinoma (ILC) or to quantify the benefit of PMRT in ILC as compared with invasive ductal carcinoma (IDC). We compared histology-specific utilization of PMRT by tumor and patient characteristics and estimated the effect of PMRT on overall and breast cancer-specific survival in ILC and IDC patients meeting American College of Radiology (ACR) criteria for PMRT.

PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results database to identify women diagnosed with ILC or IDC from 2004 to 2009 who underwent mastectomy. We assessed utilization of PMRT by T and N stage, analyzed factors associated with PMRT use, and quantified the histology-specific survival benefit of PMRT using log-rank tests and multivariate Cox regression analysis.

RESULTS: We identified 86,098 IDC and 12,703 ILC patients. Within this cohort, 18.7% of IDC patients and 26.1% of ILC met ACR criteria for PMRT. Among patients with a definite indication, PMRT was more commonly employed in ILC than in IDC (59.6% vs. 56.3%; P = .0004). Among patients with a definite indication for PMRT, radiation improved 5-year breast cancer-specific survival from 71.4% to 77.0% for IDC (P < .0001) and from 80.9% to 84.7% for ILC (P = .0003).

CONCLUSIONS: PMRT was used more commonly in ILC than in IDC. PMRT significantly improves 5-year overall survival and breast cancer-specific survival for ILC patients to a degree comparable with that seen in IDC. Moreover, among ILC and IDC patients who meet ACR criteria, PMRT appears to be significantly underutilized.}, } @article {pmid26943913, year = {2016}, author = {Takagi, M and Miki, Y and Miyashita, M and Hata, S and Yoda, T and Hirakawa, H and Sagara, Y and Rai, Y and Ohi, Y and Tamaki, K and Ishida, T and Suzuki, T and Ouchi, N and Sasano, H}, title = {Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.}, journal = {Breast cancer research and treatment}, volume = {156}, number = {1}, pages = {45-55}, doi = {10.1007/s10549-016-3739-6}, pmid = {26943913}, issn = {1573-7217}, mesh = {17-Hydroxysteroid Dehydrogenases/metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Lobular/genetics/*metabolism/pathology ; Estrogens/*biosynthesis ; Female ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Repressor Proteins/genetics ; Sulfatases/metabolism ; Sulfotransferases/metabolism ; }, abstract = {The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.}, } @article {pmid26942028, year = {2016}, author = {Kmeid, M and Kamar, FG and Nasser, S and Moukarzel, N}, title = {Metachronous, Single Metastasis to the Parotid, from Primary Breast Cancer: A Case Report and Review of the Literature.}, journal = {Case reports in oncological medicine}, volume = {2016}, number = {}, pages = {3965283}, pmid = {26942028}, issn = {2090-6706}, abstract = {Background. The parotid gland is an unusual site for metastatic disease and when metastasis occurs, it commonly originates from head and neck primaries. Spread from distant infraclavicular sites such as the breast, into the parotid, is even more unusual with very few cases reported in the literature. Case Report. We describe the case of a 65-year-old woman presenting for a rapidly enlarging right parotid mass. She had a history of an invasive ductal carcinoma of the right breast and was disease-free in the past 6 years prior to her presentation. She was thereafter diagnosed as having a solitary parotid metastasis from breast origin. A total parotidectomy was done and she was referred for adjuvant radiotherapy. Conclusion. Any parotid metastasis should be investigated, especially in patients with a prior history of cancer where the possibility of metastasis, even if improbable, should be kept in mind. Fine needle aspiration biopsy (FNAB) is the first diagnostic procedure to be done and immunocytochemistry can provide valuable information even if it is not always needed for diagnosis. Superficial parotidectomy when feasible with adjuvant radiotherapy is the preferred approach for solitary metastasis of the parotid. The prognosis, however, remains poor regardless of the treatment modality used.}, } @article {pmid26940766, year = {2016}, author = {Ulaner, GA and Goldman, DA and Gönen, M and Pham, H and Castillo, R and Lyashchenko, SK and Lewis, JS and Dang, C}, title = {Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {57}, number = {9}, pages = {1350-1356}, doi = {10.2967/jnumed.115.170456}, pmid = {26940766}, issn = {1535-5667}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; *Carboxylic Acids ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; *Cyclobutanes ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Pilot Projects ; Positron Emission Tomography Computed Tomography/*methods ; Prospective Studies ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {UNLABELLED: (18)F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that (18)F-fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of (18)F-fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC).

METHODS: Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of (18)F-fluciclovine PET/CT were compared with those of (18)F-FDG PET/CT, when available, using the concordance correlation coefficient.

RESULTS: All locally advanced breast cancers were (18)F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, (18)F-fluciclovine-avid axillary nodes were seen in 20. (18)F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent (18)F-FDG PET/CT for comparison with (18)F-fluciclovine. Concordance for metabolic tumor volume between (18)F-fluciclovine and (18)F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity (median SUVmax, 6.1; range, 4.5-10.9) greater than (18)F-FDG avidity (median SUVmax, 3.7; range, 1.8-6.0). Primary IDCs (n = 10) had a lower (18)F-fluciclovine avidity (median SUVmax, 6.8; range, 3.6-9.9) than (18)F-FDG avidity (median SUVmax, 10; range, 3.3-43.5).

CONCLUSION: (18)F-fluciclovine PET/CT demonstrates potential for imaging of both IDC and ILC, including the detection of unsuspected extraaxillary nodal metastases. The low concordance for SUVmax between (18)F-fluciclovine and (18)F-FDG suggests that these tracers measure different biologic phenomena within the tumor. The apparently higher uptake of (18)F-fluciclovine in ILC requires confirmation in a larger cohort.}, } @article {pmid26939875, year = {2016}, author = {Kweldam, CF and Kümmerlin, IP and Nieboer, D and Verhoef, EI and Steyerberg, EW and van der Kwast, TH and Roobol, MJ and van Leenders, GJ}, title = {Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {6}, pages = {630-636}, pmid = {26939875}, issn = {1530-0285}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Aged ; Biopsy ; Chi-Square Distribution ; Disease-Free Survival ; Europe ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Predictive Value of Tests ; Proportional Hazards Models ; Prostatic Neoplasms/mortality/*pathology/therapy ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.}, } @article {pmid26935613, year = {2016}, author = {Brkljačić, B and Divjak, E and Tomasović-Lončarić, Č and Tešić, V and Ivanac, G}, title = {Shear-wave sonoelastographic features of invasive lobular breast cancers.}, journal = {Croatian medical journal}, volume = {57}, number = {1}, pages = {42-50}, pmid = {26935613}, issn = {1332-8166}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Elasticity ; *Elasticity Imaging Techniques ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Tumor Burden ; }, abstract = {AIM: To evaluate shear-wave elastographic (SWE) and related gray-scale features of pure invasive lobular breast carcinoma (ILC) and compare them with invasive ductal breast cancers (IDC).

METHODS: Quantitative SWE features of mean (El-mean), maximum (El-max), minimum (El-min) elasticity values of the stiffest portion of the mass, and lesion-to-fat elasticity ratio (E-ratio) were measured in 40 patients with pure ILC and compared with 75 patients with IDC. Qualitative gray-scale features of lesion size, echogenicity, orientation, and presence of distal shadowing were determined and compared between the groups.

RESULTS: ILC were significantly larger than IDC (P=0.008) and exhibited significantly higher El-max (P=0.015) and higher El-mean (P=0.008) than IDC. ILC were significantly more often horizontally oriented, while IDC were significantly more often vertically oriented (P<0.001); ILC were significantly more often hyperechoic than IDC (P<0.001). Differences in stiffness between ILC and IDC determined by quantitative SWE parameters were present only in small tumors (≤1.5 cm in size), ie, small ILC had significantly higher El-max (P=0.030), El-mean (P=0.014), and El-min (P=0.045) than small IDC, while tumors larger than 1.5 cm had almost equal stiffness, without significant differences between the groups.

CONCLUSION: Specific histopathologic features of ILC are translated into their qualitative sonographic and quantitative sonoelastographic appearance, with higher stiffness of small ILC compared to small IDC. Gray-scale and sonoelastographic features may help in diagnosing ILC.}, } @article {pmid26930673, year = {2016}, author = {Pandya, HJ and Park, K and Chen, W and Goodell, LA and Foran, DJ and Desai, JP}, title = {Toward a Portable Cancer Diagnostic Tool Using a Disposable MEMS-Based Biochip.}, journal = {IEEE transactions on bio-medical engineering}, volume = {63}, number = {7}, pages = {1347-1353}, pmid = {26930673}, issn = {1558-2531}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA156386/CA/NCI NIH HHS/United States ; R01 CA161375/CA/NCI NIH HHS/United States ; R01 LM009239/LM/NLM NIH HHS/United States ; }, mesh = {Breast/*chemistry ; Breast Neoplasms/*diagnosis/*physiopathology ; Equipment Design ; Female ; Humans ; Micro-Electrical-Mechanical Systems/*instrumentation ; Microtechnology/*instrumentation ; Tissue Engineering ; }, abstract = {GOAL: The objective of this study is to design and develop a portable tool consisting of a disposable biochip for measuring electrothermomechanical (ETM) properties of breast tissue.

METHODS: A biochip integrated with a microheater, force sensors, and electrical sensors is fabricated using microtechnology. The sensor covers the area of 2 mm and the biochip is 10 mm in diameter. A portable tool capable of holding tissue and biochip is fabricated using 3-D printing. Invasive ductal carcinoma and normal tissue blocks are selected from cancer tissue bank in Biospecimen Repository Service at Rutgers Cancer Institute of New Jersey. The ETM properties of the normal and cancerous breast tissues (3-mm thickness and 2-mm diameter) are measured by indenting the tissue placed on the biochip integrated inside the 3-D printed tool.

RESULTS: Integrating microengineered biochip and 3-D printing, we have developed a portable cancer diagnosis device. Using this device, we have shown a statistically significant difference between cancerous and normal breast tissues in mechanical stiffness, electrical resistivity, and thermal conductivity.

CONCLUSION: The developed cancer diagnosis device is capable of simultaneous ETM measurements of breast tissue specimens and can be a potential candidate for delineating normal and cancerous breast tissue cores.

SIGNIFICANCE: The portable cancer diagnosis tool could potentially provide a deterministic and quantitative information about the breast tissue characteristics, as well as the onset and disease progression of the tissues. The tool can be potentially used for other tissue-related cancers.}, } @article {pmid26926101, year = {2016}, author = {Varma, M and Egevad, L and Algaba, F and Berney, D and Bubendorf, L and Camparo, P and Comperat, E and Erbersdobler, A and Griffiths, D and Grobholz, R and Haitel, A and Hulsbergen-van de Kaa, C and Langner, C and Loftus, B and Lopez-Beltran, A and Mayer, N and Nesi, G and Oliveira, P and Oxley, J and Rioux-Leclercq, N and Seitz, G and Shanks, J and Kristiansen, G}, title = {Intraductal carcinoma of prostate reporting practice: a survey of expert European uropathologists.}, journal = {Journal of clinical pathology}, volume = {69}, number = {10}, pages = {852-857}, doi = {10.1136/jclinpath-2016-203658}, pmid = {26926101}, issn = {1472-4146}, mesh = {Biopsy, Needle ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis ; Europe ; Humans ; Immunohistochemistry ; Male ; Neoplasm Grading ; Pathologists ; Prostate/*pathology ; Prostatic Intraepithelial Neoplasia/*diagnosis ; Prostatic Neoplasms/*diagnosis ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: It is unclear whether the reported variation in the diagnosis of intraductal carcinoma of the prostate (IDC-P) is due to variable interpretation of borderline morphology, use of different diagnostic criteria or both.

AIMS: We sought to determine the degree of variation in the diagnostic criteria and reporting rules for IDC-P in prostate biopsies employed by expert uropathologists.

METHODS: A questionnaire survey was circulated to 23 expert uropathologists from 11 European countries.

RESULTS: Criteria used for diagnosis of IDC-P included solid intraductal growth (100%), dense cribriform (96%), loose cribriform/micropapillary with nuclear size >6× normal (83%) or comedonecrosis (74%) and dilated ducts >2× normal (39%). 'Nuclear size' was interpreted as nuclear area by 74% and nuclear diameter by 21%. Pure IDC-P in needle biopsies was reported by 100% and Gleason graded by 30%. All would perform immunohistochemistry in such cases to rule out invasive cancer. An IDC-P component associated with invasive cancer would be included in the determination of tumour extent and number of cores involved by 74% and 83%, respectively. 52% would include IDC-P component when grading invasive cancer. 48% would perform immunohistochemistry in solid or cribriform nests with comedonecrosis to exclude IDC-P (17% routinely, 30% if the focus appeared to have basal cells on H&E). 48% graded such foci as Gleason pattern 5 even if immunohistochemistry demonstrated the presence of basal cells.

CONCLUSIONS: There is a need for more clarity in the definition of some of the diagnostic criteria for IDC-P as well as for greater standardisation of IDC-P reporting.}, } @article {pmid26925676, year = {2016}, author = {Khokher, S and Qureshi, MU and Mahmood, S and Sadiq, S}, title = {Determinants of Advanced Stage at Initial Diagnosis of Breast Cancer in Pakistan: Adverse Tumor Biology vs Delay in Diagnosis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {2}, pages = {759-765}, doi = {10.7314/apjcp.2016.17.2.759}, pmid = {26925676}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Carcinoma, Lobular/*diagnosis/metabolism ; *Delayed Diagnosis ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most frequent cancer of women in Pakistan with the majority presenting with stage III or IV lesionsat initial diagnosis. Patient and health system related factors are well known determinants of delay in presentation and diagnosis. Additionally, breast cancer being a heterogeneous disease, the various molecular subtypes featuring different aggressiveness also need to be considered. The present study evaluated the association of stage at initial diagnosis of breast cancer with these two factors in local women at a tertiary level health care facility in Lahore, Pakistan.

MATERIALS AND METHODS: Patient and tumor features were recorded separately during diagnostic workup in Breast Clinics at INMOL and at Services Hospital, Lahore. Data were entered in MS Excel and analyzed by descriptive statistics and Chi-Square test.

RESULTS: Among the 261 patients, 64% were staged as late breast cancer (LBC), the mean age was 46.8 with standard deviation of 13 years. Some 92% had invasive ductal carcinoma (IDC), 61% had luminal types (LT) of non-aggressive tumor while 39% had the non-luminal types (NLT) of of HER2-enriched or basal aggressive tumors. While 70% of patients presented within one year of symptomatic disease (early report group "ERG"), 30% reported after a mean delay of 4 years with a standard deviation of 3.75 years. The stage distribution among ERG patients was not statistically different from those reporting late (P=0.123). Statistically larger proportion of patients with NLT presented as LBC as compared to the LT (P =0.034). Among the ERG, statistically different stage distribution of disease was observed for the NLT versus LT (P=0.047). Among those presenting late, this difference was insignificant (P=0.416).

CONCLUSIONS: Breast cancer is a distinct disease in Pakistan with a high frequency of aggressive molecular types affecting younger women, with the majority presenting as LBC. Association of NLT with higher stage at diagnosis is statistically significant whereas time delay in diagnosis is not. Further research is required to define the risk profile and features in local patients. The burden of LBC can be reduced by promoting breast health awareness and by establishing easily accessible dedicated breast care set ups in the hospitals.}, } @article {pmid26914858, year = {2016}, author = {Davis, D and Soref, A and Villalobos, JG and Mikulincer, M}, title = {Priming states of mind can affect disclosure of threatening self-information: Effects of self-affirmation, mortality salience, and attachment orientations.}, journal = {Law and human behavior}, volume = {40}, number = {4}, pages = {351-361}, doi = {10.1037/lhb0000184}, pmid = {26914858}, issn = {1573-661X}, mesh = {*Arabs ; *Disclosure ; Humans ; Israel ; Jews ; Surveys and Questionnaires ; }, abstract = {Interviewers often face respondents reluctant to disclose sensitive, embarrassing or potentially damaging information. We explored effects of priming 5 states of mind on willingness to disclose: including 2 expected to facilitate disclosure (self-affirmation, attachment security), and 3 expected to inhibit disclosure (self-disaffirmation, attachment insecurity, mortality salience). Israeli Jewish participants completed a survey including a manipulation of 1 of these states of mind, followed by questions concerning hostile thoughts and behaviors toward the Israeli Arab outgroup, past minor criminal behaviors, and socially undesirable traits and behaviors. Self-affirmation led to more disclosures of all undesirable behaviors than neutral priming, whereas self-disaffirmation led to less disclosures. Mortality salience led to fewer disclosures of socially undesirable and criminal behaviors compared to neutral priming, but more disclosures of hostile thoughts and behaviors toward Israeli Arabs. Security priming facilitated disclosure of hostile attitudes toward Israeli Arabs. However, neither security nor insecurity priming had any other significant effects. (PsycINFO Database Record}, } @article {pmid26914349, year = {2016}, author = {Wong, L and Wilson, RM and Snapp, WK and Bole, R and Vyas, KS}, title = {Nipple Pathology in Total Skin-Sparing Mastectomy: Implications for Immediate Reconstruction.}, journal = {Annals of plastic surgery}, volume = {76 Suppl 4}, number = {}, pages = {S340-3}, doi = {10.1097/SAP.0000000000000762}, pmid = {26914349}, issn = {1536-3708}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*methods ; *Mastectomy, Subcutaneous ; Middle Aged ; Nipples/*pathology/surgery ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: The management of occult tumor involvement of the nipple during total skin-sparing mastectomy (TSSM) and immediate reconstruction is not well addressed in the literature. We reviewed our experience with positive nipple core biopsies, comparing outcomes of different management options.

METHODS: Mastectomy and implant/expander reconstructions over a 5-year period were reviewed. Patient characteristics, type of mastectomy, and complications were analyzed. Patients were grouped by type of mastectomy/immediate reconstruction and delayed reconstruction to compare outcomes. Positive intraoperative core nipple biopsy cases formed a subset of the TSSM group.

RESULTS: Forty-four of 240 (18%) cases were TSSMs performed through inferolateral incisions. All were reconstructed immediately, 24 with tissue expanders and 20 with implants. Major complications (necrosis, infection, seroma) were significantly lower than for skin-sparing mastectomies, but higher than delayed reconstruction. One case of full thickness nipple necrosis occurred. Seven of the TSSM group had positive core nipple biopsies (16%). Three of these patients underwent nipple excision and tissue expander placement at the initial surgery, of which 2 developed subsequent mastectomy skin flap necrosis requiring explantation. A third patient underwent staged nipple excision without complication. The remaining 3 patients underwent delayed nipple resection at the time of tissue expander replacement without complication. Pathology in the nipple core was invasive ductal carcinoma and ductal carcinoma in situ. No TSSM patients have developed local recurrence at follow-up.

CONCLUSIONS: Concurrent excision of the nipple and an inferolateral incision increase the incidence of skin flap necrosis. Delaying nipple excision may prove to be a safer option.}, } @article {pmid26909315, year = {2016}, author = {Schäfer, M and Oeing, CU and Rohm, M and Baysal-Temel, E and Lehmann, LH and Bauer, R and Volz, HC and Boutros, M and Sohn, D and Sticht, C and Gretz, N and Eichelbaum, K and Werner, T and Hirt, MN and Eschenhagen, T and Müller-Decker, K and Strobel, O and Hackert, T and Krijgsveld, J and Katus, HA and Berriel Diaz, M and Backs, J and Herzig, S}, title = {Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia.}, journal = {Molecular metabolism}, volume = {5}, number = {2}, pages = {67-78}, pmid = {26909315}, issn = {2212-8778}, abstract = {OBJECTIVES: Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown.

METHODS AND RESULTS: By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven "cachexokines", including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models.

CONCLUSIONS: As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia.}, } @article {pmid26907291, year = {2016}, author = {Khan, MR and Khalilian, A and Kang, SW}, title = {Fast, Highly-Sensitive, and Wide-Dynamic-Range Interdigitated Capacitor Glucose Biosensor Using Solvatochromic Dye-Containing Sensing Membrane.}, journal = {Sensors (Basel, Switzerland)}, volume = {16}, number = {2}, pages = {265}, pmid = {26907291}, issn = {1424-8220}, mesh = {Biosensing Techniques/*methods ; Coloring Agents/chemistry ; Electrodes ; Glucose/*analysis ; }, abstract = {In this paper, we proposed an interdigitated capacitor (IDC)-based glucose biosensor to measure different concentrations of glucose from 1 μM to 1 M. We studied four different types of solvatochromic dyes: Auramine O, Nile red, Rhodamine B, and Reichardt's dye (R-dye). These dyes were individually incorporated into a polymer [polyvinyl chloride (PVC)] and N,N-Dimethylacetamide (DMAC) solution to make the respective dielectric/sensing materials. To the best of our knowledge, we report for the first time an IDC glucose biosensing system utilizing a solvatochromic-dye-containing sensing membrane. These four dielectric or sensing materials were individually placed into the interdigitated electrode (IDE) by spin coating to make four IDC glucose biosensing elements. The proposed IDC glucose biosensor has a high sensing ability over a wide dynamic range and its sensitivity was about 23.32 mV/decade. It also has fast response and recovery times of approximately 7 s and 5 s, respectively, excellent reproducibility with a standard deviation of approximately 0.023, highly stable sensing performance, and real-time monitoring capabilities. The proposed IDC glucose biosensor was compared with an IDC, potentiometric, FET, and fiber-optic glucose sensor with respect to response time, dynamic range width, sensitivity, and linearity. We observed that the designed IDC glucose biosensor offered excellent performance.}, } @article {pmid26904685, year = {2016}, author = {Wu, Y and Gu, Y and Guo, S and Dai, Q and Zhang, W}, title = {Expressing Status and Correlation of ARID1A and Histone H2B on Breast Cancer.}, journal = {BioMed research international}, volume = {2016}, number = {}, pages = {7593787}, pmid = {26904685}, issn = {2314-6141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Chromatin/genetics ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Histones/*biosynthesis/genetics ; Humans ; Middle Aged ; Mutation ; Nuclear Proteins/*biosynthesis/genetics ; Prognosis ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {ARID1A is one of the important cancer-related genes and regulates transcription of certain genes by altering chromatin structure. Inactivated mutations and decreased expression of ARID1A gene have been reported in several kinds of cancer. Histone H2B is a major component of chromatin and encoded by HIST1H2BE. The goal of the study is to evaluate expressing status of ARID1A and H2B as well as their correlation on breast cancer. Gene expression profiles of ARID1A and H2B on Oncomine database are analyzed. Tissue microarray of breast cancer was used for examination of ARID1A and H2B expression by immunohistochemistry. As a result, the disagreement of ARID1A expression was found, while HIST1H2BE expression is elevated in 4 out of 5 datasets on Oncomine database. There were 15 cases (20%) of breast cancers that were positive for ARID1A. Fifty-eight out of 75 cases of breast cancer (77.3%) were highly expressed for H2B protein and 17 cases (22.7%) were low expressed for H2B protein. All cases with ARID1A expression are overlapped with H2B high expression. Among 15 cases with ARID1A and H2B coexpression, 13 are invasive ductal carcinoma and 2 are mucinous carcinoma. Our results indicate that ARID1A gene may be involved in carcinogenesis of some subtypes of breast cancer.}, } @article {pmid26902100, year = {2016}, author = {Ehling, J and Misiewicz, M and von Stillfried, S and Möckel, D and Bzyl, J and Pochon, S and Lederle, W and Knuechel, R and Lammers, T and Palmowski, M and Kiessling, F}, title = {In situ validation of VEGFR-2 and α v ß 3 integrin as targets for breast lesion characterization.}, journal = {Angiogenesis}, volume = {19}, number = {2}, pages = {245-254}, pmid = {26902100}, issn = {1573-7209}, support = {309495/ERC_/European Research Council/International ; }, mesh = {Breast Neoplasms/*metabolism/*pathology ; Endothelial Cells/metabolism ; Female ; Humans ; Integrin alphaVbeta3/*metabolism ; Middle Aged ; Reproducibility of Results ; Vascular Endothelial Growth Factor Receptor-2/*metabolism ; }, abstract = {Vascular endothelial growth factor receptor 2 (VEGFR-2) and α v ß 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, α v ß 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated. To this end, tissue sections of breast cancer (n = 40), pre-invasive ductal carcinoma in situ (DCIS; n = 8), fibroadenoma (n = 40), radial scar (n = 6) and normal breast tissue (n = 40) were used to quantify (1) endothelial VEGFR-2, (2) endothelial α v ß 3 integrin and (3) total α v ß 3 integrin expression, as well as (4) the vascular area fraction. Sensitivity and specificity to differentiate benign from malignant lesions were calculated for each marker by receiver operating characteristics (ROC) analyses. Whereas vessel density, as commonly used, did not significantly differ between benign and malignant lesions (AUROC: 0.54), VEGFR-2 and α v ß 3 integrin levels were gradually up-regulated in carcinoma versus fibroadenoma versus healthy tissue. The highest diagnostic accuracy for differentiating carcinoma from fibroadenoma was found for total α v ß 3 integrin expression (AUROC: 0.76), followed by VEGFR-2 (AUROC: 0.71) and endothelial α v ß 3 integrin expression (AUROC: 0.68). In conclusion, total α v ß 3 integrin expression is the best discriminator between breast cancer, fibroadenoma and normal breast tissue. With respect to vascular targeting and molecular imaging of angiogenesis, endothelial VEGFR-2 appeared to be slightly superior to endothelial α v ß 3 for differentiating benign from cancerous lesions.}, } @article {pmid26897954, year = {2015}, author = {Matsuoka, S and Ishii, T and Miyazawa, S and Mizutani, T and Ito, K and Kamimura, S and Matsumoto, N and Moriyama, M and Takayama, T}, title = {Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils.}, journal = {Hepato-gastroenterology}, volume = {62}, number = {139}, pages = {683-687}, pmid = {26897954}, issn = {0172-6390}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Embolization, Therapeutic/adverse effects/*instrumentation ; Equipment Design ; Female ; Humans ; Hypersplenism/blood/diagnosis/etiology/*therapy ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Platelet Count ; *Splenic Artery ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC).

METHODOLOGY: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C-reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment.

RESULTS: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008).

CONCLUSION: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment.}, } @article {pmid26891048, year = {2016}, author = {Shin, S and Pak, K and Park, DY and Kim, SJ}, title = {Tumor Heterogeneity Assessed by 18F-FDG PET/CT Is Not Significantly Associated with Nodal Metastasis in Breast Cancer Patients.}, journal = {Oncology research and treatment}, volume = {39}, number = {1-2}, pages = {61-66}, doi = {10.1159/000442760}, pmid = {26891048}, issn = {2296-5262}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography/*methods ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; Tumor Burden ; }, abstract = {INTRODUCTION: The purpose of this study was to evaluate the association of tumor heterogeneity as assessed by positron emission tomography/computed tomography (PET/CT) with pathological factors of breast cancer, and the prediction of nodal metastasis through tumor heterogeneity.

METHODS: From January 2013 to December 2013, 102 patients with invasive ductal carcinoma of the breast were enrolled into this study. [18F]Fluorodeoxyglucose PET/CT was performed before surgery. The metabolic tumor volume (MTV) of each lesion was calculated and a series of standardized uptake value (SUV) thresholds (e.g. 40%, 50%, 60%, 70%, and 80% of SUVmax) was obtained. A threshold-volume (dV/dT) curve was acquired by plotting thresholds to MTV values automatically calculated with these thresholds. Tumor heterogeneity was calculated from the slope of the threshold-volume curve and defined as heterogeneity factor (HF).

RESULTS: HF differed significantly according to T stage (p < 0.0001), N stage (p = 0.0131) and American Joint Committee on Cancer (AJCC) stage (p = 0.0006). Among the pathological parameters, dermal lymphatic involvement (p = 0.0039) showed the significant correlations with HF. Lymphovascular invasion (p = 0.0005) was the only independent factor for predicting nodal metastasis.

CONCLUSIONS: Tumor heterogeneity measured by 18F-FDG PET/CT is significantly associated with dermal lymphatic involvement. However, PET might not be able to predict nodal metastasis in breast cancer.}, } @article {pmid26886800, year = {2016}, author = {Kuhlwilm, M and Gronau, I and Hubisz, MJ and de Filippo, C and Prado-Martinez, J and Kircher, M and Fu, Q and Burbano, HA and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Rudan, P and Brajkovic, D and Kucan, Ž and Gušic, I and Marques-Bonet, T and Andrés, AM and Viola, B and Pääbo, S and Meyer, M and Siepel, A and Castellano, S}, title = {Ancient gene flow from early modern humans into Eastern Neanderthals.}, journal = {Nature}, volume = {530}, number = {7591}, pages = {429-433}, pmid = {26886800}, issn = {1476-4687}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; GM102192/GM/NIGMS NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; }, mesh = {Altitude ; Animals ; Bayes Theorem ; Chromosomes, Human, Pair 21/genetics ; Croatia/ethnology ; Gene Flow/*genetics ; Genome, Human/genetics ; Genomics ; Haplotypes/genetics ; Heterozygote ; Humans ; Hybridization, Genetic/genetics ; Neanderthals/*genetics ; Phylogeny ; Population Density ; Siberia ; Spain/ethnology ; Time Factors ; }, abstract = {It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.}, } @article {pmid26884359, year = {2016}, author = {Petridis, C and Brook, MN and Shah, V and Kohut, K and Gorman, P and Caneppele, M and Levi, D and Papouli, E and Orr, N and Cox, A and Cross, SS and Dos-Santos-Silva, I and Peto, J and Swerdlow, A and Schoemaker, MJ and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Benitez, J and González-Neira, A and Tessier, DC and Vincent, D and Li, J and Figueroa, J and Kristensen, V and Borresen-Dale, AL and Soucy, P and Simard, J and Milne, RL and Giles, GG and Margolin, S and Lindblom, A and Brüning, T and Brauch, H and Southey, MC and Hopper, JL and Dörk, T and Bogdanova, NV and Kabisch, M and Hamann, U and Schmutzler, RK and Meindl, A and Brenner, H and Arndt, V and Winqvist, R and Pylkäs, K and Fasching, PA and Beckmann, MW and Lubinski, J and Jakubowska, A and Mulligan, AM and Andrulis, IL and Tollenaar, RA and Devilee, P and Le Marchand, L and Haiman, CA and Mannermaa, A and Kosma, VM and Radice, P and Peterlongo, P and Marme, F and Burwinkel, B and van Deurzen, CH and Hollestelle, A and Miller, N and Kerin, MJ and Lambrechts, D and Floris, G and Wesseling, J and Flyger, H and Bojesen, SE and Yao, S and Ambrosone, CB and Chenevix-Trench, G and Truong, T and Guénel, P and Rudolph, A and Chang-Claude, J and Nevanlinna, H and Blomqvist, C and Czene, K and Brand, JS and Olson, JE and Couch, FJ and Dunning, AM and Hall, P and Easton, DF and Pharoah, PD and Pinder, SE and Schmidt, MK and Tomlinson, I and Roylance, R and García-Closas, M and Sawyer, EJ}, title = {Genetic predisposition to ductal carcinoma in situ of the breast.}, journal = {Breast cancer research : BCR}, volume = {18}, number = {1}, pages = {22}, pmid = {26884359}, issn = {1465-542X}, support = {CA54281/CA/NCI NIH HHS/United States ; CA128978/CA/NCI NIH HHS/United States ; R01 CA176785/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; C12292/A11174/CRUK_/Cancer Research UK/United Kingdom ; C5047/A10692/CRUK_/Cancer Research UK/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; C5047/A15007/CRUK_/Cancer Research UK/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; U19 CA148065/CA/NCI NIH HHS/United States ; C1281/A12014/CRUK_/Cancer Research UK/United Kingdom ; C8197/A16565/CRUK_/Cancer Research UK/United Kingdom ; 10119/CRUK_/Cancer Research UK/United Kingdom ; 10124/CRUK_/Cancer Research UK/United Kingdom ; CA116201/CA/NCI NIH HHS/United States ; P30 CA016056-32/CA/NCI NIH HHS/United States ; /CAPMC/CIHR/Canada ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; U01 CA116167/CA/NCI NIH HHS/United States ; C5047/A8384/CRUK_/Cancer Research UK/United Kingdom ; C1287/A 10710/CRUK_/Cancer Research UK/United Kingdom ; CA116167/CA/NCI NIH HHS/United States ; CA176785/CA/NCI NIH HHS/United States ; U19 CA148537/CA/NCI NIH HHS/United States ; R01 CA116167/CA/NCI NIH HHS/United States ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; U19 CA148112/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; CA098758/CA/NCI NIH HHS/United States ; MC_PC_14105/MRC_/Medical Research Council/United Kingdom ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA164973/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cyclin D1/*genetics ; Female ; *Genetic Association Studies ; Genotype ; Humans ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.

METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip.

RESULTS: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8).

CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.}, } @article {pmid26881597, year = {2015}, author = {Mukhopadhyay, T and Nandi, M and Bhattacharya, S and Khan, EM}, title = {Contralateral contiguous tuberculous lymphadenitis in a case of right breast carcinoma--Diagnostic dilemma.}, journal = {Journal of cancer research and therapeutics}, volume = {11}, number = {4}, pages = {1026}, doi = {10.4103/0973-1482.150410}, pmid = {26881597}, issn = {1998-4138}, mesh = {Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/diagnostic imaging/*pathology ; Middle Aged ; Prognosis ; Radiopharmaceuticals ; Tuberculosis, Lymph Node/*diagnosis/surgery ; }, abstract = {Coexistence of tuberculosis (TB) in the breast or axillary lymph nodes with breast carcinoma though rare is not unknown. A 55-year-old woman presented with right axillary and left supraclavicular lymphadenopathies with no detectable lesion in either breasts or left axilla. Right axillary lymph node excision biopsy revealed metastatic adenocarcinoma. Diagnostic workup showed intense fluorodeoxyglucose (FDG)-avid lymph nodes on the left side neck at level V, supraclavicular, axillary, subpectoral and para-aortic regions, and low FDG activity in the right breast. Core biopsy of right breast lesion was reported as invasive ductal carcinoma and cytology of multiple left axillary lymphadenopathies as reactive hyperplasia. Excision biopsy of the supraclavicular lymph nodes unveiled the diagnosis of TB. She underwent right-modified radical mastectomy followed by external beam radiotherapy, has completed antituberculous treatment and is on follow-up. Extrapulmonary TB though uncommon; may be found in certain cases. Clinicians must be aware of its existence.}, } @article {pmid26876209, year = {2016}, author = {Kim, DY and Helfman, DM}, title = {Loss of MLCK leads to disruption of cell-cell adhesion and invasive behavior of breast epithelial cells via increased expression of EGFR and ERK/JNK signaling.}, journal = {Oncogene}, volume = {35}, number = {34}, pages = {4495-4508}, pmid = {26876209}, issn = {1476-5594}, mesh = {Actin Cytoskeleton/metabolism ; Breast/*pathology ; Breast Neoplasms/enzymology/*pathology ; Cell Adhesion ; Cell Aggregation ; Cell Line, Tumor ; Cell Movement ; Cells, Cultured ; Epithelial Cells/pathology ; ErbB Receptors/*physiology ; Female ; Humans ; MAP Kinase Signaling System/*physiology ; Myosin-Light-Chain Kinase/*physiology ; Neoplasm Invasiveness ; RNA, Small Interfering/genetics ; }, abstract = {Myosin light chain kinase (MLCK) expression is downregulated in breast cancer, including invasive ductal carcinoma compared with ductal breast carcinoma in situ and metastatic breast tumors. However, little is known about how loss of MLCK expression contributes to tumor progression. MLCK is a component of the actin cytoskeleton and its known role is the phosphorylation of the regulatory light chain of myosin II. To gain insights into the role of MLCK in breast cancer, we perturbed its function using small interfering RNA (siRNA) or pharmacological inhibition in untransformed breast epithelial cells (MCF10A). Loss of MLCK by siRNAs led to increased cell migration and invasion, disruption of cell-cell adhesions and enhanced formation of focal adhesions at the leading edge of migratory cells. In addition, downregulation of MLCK cooperated with HER2 in MCF10A cells to promote cell migration and invasion and low levels of MLCK is associated with a poor prognosis in HER2-positive breast cancer patients. Associated with these altered migratory behaviors were increased expression of epidermal growth factor receptor and activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways in MLCK downregulated MCF10A cells. By contrast, inhibition of the kinase function of MLCK using pharmacological agents inhibited cell migration and invasion, and did not affect cellular adhesions. Our results show that loss of MLCK contributes to the migratory properties of epithelial cells resulting from changes in cell-cell and cell-matrix adhesions, and increased epidermal growth factor receptor signaling. These findings suggest that decreased expression of MLCK may have a critical role during tumor progression by facilitating the metastatic potential of tumor cells.}, } @article {pmid26876108, year = {2016}, author = {Silva-Vergara, C and Fontdevila, J and Descarrega, J and Burdio, F and Yoon, TS and Grande, L}, title = {Oncological outcomes of lipofilling breast reconstruction: 195 consecutive cases and literature review.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {69}, number = {4}, pages = {475-481}, doi = {10.1016/j.bjps.2015.12.029}, pmid = {26876108}, issn = {1878-0539}, mesh = {Adipose Tissue/*transplantation ; Adult ; Breast Neoplasms/*surgery ; Female ; Humans ; Mammaplasty/*methods ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Postoperative Complications/epidemiology ; Spain/epidemiology ; Treatment Outcome ; }, abstract = {INTRODUCTION: Lipofilling has become a widely used procedure in breast reconstruction after mastectomy or breast-conserving treatment. The possibility that this technique may increase stimulation of cancer development between the potential tumor bed and the lipoaspirates grafts has been raised regarding its safety. The aim of this study was to identify the oncological risks associated with this procedure in our institution.

METHODS: Between years 2007 and 2014 we record 195 consecutive patients with fat grafting technique for reconstructive purpose after breast cancer treatment. The loco-regional recurrence (LRR) as first event of relapse was the primary end point of this study.

RESULTS: We performed 319 lipofilling procedures in 132 mastectomy and 63 breast-conserving surgery patients. Invasive carcinoma represents 81.6% of the series. The median follow-up from primary cancer surgery and fat grafting was 74 and 31 months respectively. Median time between oncologic surgery and lipofilling was 36 months. The authors observed a complication rate of 8.2%, most of them liponecrosis and oil cysts (7.2%). Four local, 2 regional and 4 distant recurrences were observed as first event of relapse in 10 patients with invasive ductal carcinoma. The loco-regional recurrence rate was 3.1% (1.08% per year).

CONCLUSIONS: Although larger prospective trials are needed, these results support the fact that lipofilling following breast cancer treatment leads to a very low rate of complications and similar to other authors, it does not seem to interfere in patient's oncological prognosis when compared with prior publications.}, } @article {pmid26871889, year = {2016}, author = {Miri, AK and Muja, N and Kamranpour, NO and Lepry, WC and Boccaccini, AR and Clarke, SA and Nazhat, SN}, title = {Ectopic bone formation in rapidly fabricated acellular injectable dense collagen-Bioglass hybrid scaffolds via gel aspiration-ejection.}, journal = {Biomaterials}, volume = {85}, number = {}, pages = {128-141}, doi = {10.1016/j.biomaterials.2016.01.047}, pmid = {26871889}, issn = {1878-5905}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Biocompatible Materials/chemistry ; Ceramics/*chemistry ; Durapatite/chemistry ; Fibrillar Collagens/*chemistry ; Gels/chemistry ; Male ; Osteoblasts/cytology ; Osteogenesis/*physiology ; Rats ; Rats, Inbred F344 ; Spectroscopy, Fourier Transform Infrared ; Tissue Engineering/*methods ; Tissue Scaffolds/*chemistry ; }, abstract = {Gel aspiration-ejection (GAE) has recently been introduced as an effective technique for the rapid production of injectable dense collagen (IDC) gel scaffolds with tunable collagen fibrillar densities (CFDs) and microstructures. Herein, a GAE system was applied for the advanced production and delivery of IDC and IDC-Bioglass(®) (IDC-BG) hybrid gel scaffolds for potential bone tissue engineering applications. The efficacy of GAE in generating mineralizable IDC-BG gels (from an initial 75-25 collagen-BG ratio) produced through needle gauge numbers 8G (3.4 mm diameter and 6 wt% CFD) and 14G (1.6 mm diameter and 14 wt% CFD) was investigated. Second harmonic generation (SHG) imaging of as-made gels revealed an increase in collagen fibril alignment with needle gauge number. In vitro mineralization of IDC-BG gels was confirmed where carbonated hydroxyapatite was detected as early as day 1 in simulated body fluid, which progressively increased up to day 14. In vivo mineralization of, and host response to, acellular IDC and IDC-BG gel scaffolds were further investigated following subcutaneous injection in adult rats. Mineralization, neovascularization and cell infiltration into the scaffolds was enhanced by the addition of BG and at day 21 post injection, there was evidence of remodelling of granulation tissue into woven bone-like tissue in IDC-BG. SHG imaging of explanted scaffolds indicated collagen fibril remodelling through cell infiltration and mineralization over time. In sum, the results suggest that IDC-BG hybrid gels have osteoinductive properties and potentially offer a novel therapeutic approach for procedures requiring the injectable delivery of a malleable and dynamic bone graft that mineralizes under physiological conditions.}, } @article {pmid26870178, year = {2016}, author = {Zhou, D and Zhang, M and Xu, P and Yu, Y and Ye, G and Zhang, L and Wu, A}, title = {Expression of pigment epithelium-derived factor is associated with a good prognosis and is correlated with epithelial-mesenchymal transition-related genes in infiltrating ductal breast carcinoma.}, journal = {Oncology letters}, volume = {11}, number = {1}, pages = {116-124}, pmid = {26870178}, issn = {1792-1074}, abstract = {Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E-cadherin, vimentin, Snail and nuclear factor-κB (NF-κB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-κB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-κB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF- and E-cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF-κB-positive tumors. Vimentin, E-cadherin and NF-κB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation.}, } @article {pmid26868906, year = {2016}, author = {Mao, X and He, J and Li, T and Lu, Z and Sun, J and Meng, Y and Abliz, Z and Chen, J}, title = {Application of imaging mass spectrometry for the molecular diagnosis of human breast tumors.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {21043}, pmid = {26868906}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Breast Neoplasms/diagnosis/metabolism ; *Carcinoma, Ductal/diagnosis/metabolism ; Female ; Humans ; *Lipid Metabolism ; Lipids/*analysis ; Mass Spectrometry/*methods ; Middle Aged ; }, abstract = {Distinguishing breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS) is a key step in breast surgery, especially to determine whether DCIS is associated with tumor cell micro-invasion. However, there is currently no reliable method to obtain molecular information for breast tumor analysis during surgery. Here, we present a novel air flow-assisted ionization (AFAI) mass spectrometry imaging method that can be used in ambient environments to differentiate breast cancer by analyzing lipids. In this study, we demonstrate that various subtypes and histological grades of IDC and DCIS can be discriminated using AFAI-MSI: phospholipids were more abundant in IDC than in DCIS, whereas fatty acids were more abundant in DCIS than in IDC. The classification of specimens in the subtype and grade validation sets showed 100% and 78.6% agreement with the histopathological diagnosis, respectively. Our work shows the rapid classification of breast cancer utilizing AFAI-MSI. This work suggests that this method could be developed to provide surgeons with nearly real-time information to guide surgical resections.}, } @article {pmid26864441, year = {2017}, author = {Rayne, S and Schnippel, K and Thomson, J and Reid, J and Benn, C}, title = {Male Breast Cancer Has Limited Effect on Survivor's Perceptions of Their Own Masculinity.}, journal = {American journal of men's health}, volume = {11}, number = {2}, pages = {246-252}, pmid = {26864441}, issn = {1557-9891}, mesh = {Adult ; Breast Neoplasms, Male/*psychology ; Cancer Survivors/*psychology ; Health Status ; Humans ; Male ; *Masculinity ; Middle Aged ; Neoplasm Staging ; Quality of Life/*psychology ; *Self Concept ; }, abstract = {The purpose of the current study was to describe male breast cancer in Johannesburg, South Africa, and assess whether male breast cancer patients' perception of their own masculinity was affected by having a cancer commonly seen in women. A retrospective file review was carried out at two hospitals, one private and one government, of male breast cancer patients from 2007 to 2012 followed by a telephone survey of patients identified during review. Of approximately 3,000 breast cancer patients seen in the 5 years reviewed, 23 cases of male breast cancer were identified. Most were diagnosed with invasive ductal carcinoma (n = 19, 83%). Stage at presentation was from stages 0 to 3 (Stage 0 [ n = 2, 9%], Stage 1 [ n = 3, 13%], Stage 2 [ n = 12, 52%], Stage 3 [ n = 6, 26%]) and no patients were metastatic at presentation. The telephonic survey was completed by 18 patients (78%). Nearly all (n = 17/18) shared their diagnosis with family and close friends. Two thirds of patients delayed presentation and government hospital patients were more likely to present later than private sector hospital patients. Although most male breast cancer patients sampled did not perceive the breast cancer diagnosis as affecting their masculinity, Black men and those treated in government hospitals were less likely to be aware of male breast cancer, and were more likely to have their perception of their own masculinity affected.}, } @article {pmid26864379, year = {2016}, author = {Nakash, O and Nagar, M and Lurie, I}, title = {The Association Between Postnatal Depression, Acculturation and Mother-Infant Bond Among Eritrean Asylum Seekers in Israel.}, journal = {Journal of immigrant and minority health}, volume = {18}, number = {5}, pages = {1232-1236}, pmid = {26864379}, issn = {1557-1920}, mesh = {Acculturation ; Adult ; Depression, Postpartum/diagnosis/*ethnology ; Eritrea/ethnology ; Female ; Humans ; Infant ; Israel ; Mother-Child Relations/*ethnology/*psychology ; Mothers/*psychology ; Refugees/*psychology ; Socioeconomic Factors ; Vulnerable Populations/ethnology/psychology ; }, abstract = {We examined the association between postnatal depression (PND), acculturation and mother-infant bond among 38 Eritrean asylum seekers in Israel, who were within 6 months of delivery. Participants completed a survey in their native language. A high rate of women (81.6 %) met the clinical threshold for PND on the Edinburgh Postnatal Depression Scale. Higher severity of PND (partial r = -.64, p < .001), higher identification with Israeli culture (partial r = -.45, p = .02), and lower quality of romantic relationship were associated with impaired mother-infant bond (partial r = .58, p = .002). Findings highlight the need to establish services to screen and treat PND among this vulnerable population in the receiving countries.}, } @article {pmid26864079, year = {2016}, author = {Gulvin, J and Aboulafia, DM}, title = {Squamous Cell Cancer of Unknown Primary and Primary Breast Cancer in an HIV-Infected Woman: The Importance of Cancer Screening for People Living with HIV/AIDS.}, journal = {Journal of the International Association of Providers of AIDS Care}, volume = {15}, number = {3}, pages = {194-200}, doi = {10.1177/2325957416629550}, pmid = {26864079}, issn = {2325-9574}, mesh = {*Breast Neoplasms/complications/diagnostic imaging ; *Carcinoma, Squamous Cell/complications/diagnostic imaging/secondary ; Early Detection of Cancer ; Female ; Groin/diagnostic imaging/pathology ; HIV Infections/*complications ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Papillomavirus Infections ; }, abstract = {People living with HIV/AIDS (PLWHA) are surviving longer, with an increased risk of cancer. Cancer screening strategies in PLWHA are lacking. We describe the case of a woman with a history of AIDS, who had a nondetectable viral load on treatment. She is an activist, promoting HIV care, but had not undergone routine screening for breast, cervical, or colonic neoplasia. She presented with a left groin mass, which on biopsy proved to be a p16 immuno-histochemical positive squamous cell carcinoma. Anal and cervicovaginal examinations did not show invasive cancer, although high-resolution anoscopy identified high-grade anal dysplasia. A mammogram followed by magnetic resonance imaging showed invasive ductal carcinoma. Her breast cancer was treated with lumpectomy, adjuvant brachytherapy and chemotherapy. The left groin tumor was treated with chemo-radiation. Herein, we also review medical literature concerning anal, cervical, breast, colorectal, and lung cancer screening for PLWHA, which is important for our aging population of PLWHA.}, } @article {pmid26858037, year = {2016}, author = {Zhu, L and Mok, S and Imwong, M and Jaidee, A and Russell, B and Nosten, F and Day, NP and White, NJ and Preiser, PR and Bozdech, Z}, title = {New insights into the Plasmodium vivax transcriptome using RNA-Seq.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {20498}, pmid = {26858037}, issn = {2045-2322}, support = {093956//Wellcome Trust/United Kingdom ; }, mesh = {Chromosomes/genetics/metabolism ; *High-Throughput Nucleotide Sequencing ; Humans ; Plasmodium vivax/*genetics/metabolism ; RNA, Protozoan/biosynthesis/*genetics ; Transcriptome/*physiology ; }, abstract = {Historically seen as a benign disease, it is now becoming clear that Plasmodium vivax can cause significant morbidity. Effective control strategies targeting P. vivax malaria is hindered by our limited understanding of vivax biology. Here we established the P. vivax transcriptome of the Intraerythrocytic Developmental Cycle (IDC) of two clinical isolates in high resolution by Illumina HiSeq platform. The detailed map of transcriptome generates new insights into regulatory mechanisms of individual genes and reveals their intimate relationship with specific biological functions. A transcriptional hotspot of vir genes observed on chromosome 2 suggests a potential active site modulating immune evasion of the Plasmodium parasite across patients. Compared to other eukaryotes, P. vivax genes tend to have unusually long 5' untranslated regions and also present multiple transcription start sites. In contrast, alternative splicing is rare in P. vivax but its association with the late schizont stage suggests some of its significance for gene function. The newly identified transcripts, including up to 179 vir like genes and 3018 noncoding RNAs suggest an important role of these gene/transcript classes in strain specific transcriptional regulation.}, } @article {pmid26853508, year = {2016}, author = {Guvenc, I and Akay, S and Ince, S and Yildiz, R and Kilbas, Z and Oysul, FG and Tasar, M}, title = {Apparent diffusion coefficient value in invasive ductal carcinoma at 3.0 Tesla: is it correlated with prognostic factors?.}, journal = {The British journal of radiology}, volume = {89}, number = {1060}, pages = {20150614}, pmid = {26853508}, issn = {1748-880X}, mesh = {Adult ; Aged ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging/methods ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; }, abstract = {OBJECTIVE: To investigate the correlation between apparent diffusion coefficient (ADC) values and prognostic factors in patients with invasive ductal carcinoma (IDC).

METHODS: 48 lesions belonging to 47 patients with histopathologically proven IDC were examined using conventional MR and diffusion-weighted imaging at a 3.0-T system. All of the patients had modified radical mastectomies or breast-sparing surgery plus axillary lymph node dissection. The ADC values acquired from the ADC maps consisted of six different b-values (0, 50, 100, 500, 1000 and 1500 s mm(-2)) and were compared with the patients' ages, tumour size, histological grade of the lesions, tumour localization, lesions' distance to skin surface and nipples, the existence of axillary lymph node involvement, the number of involved axillary lymph nodes, oestrogen/progesterone receptor status, peritumoral lymphovascular invasion status and the existence of human epidermal growth factor 2 (c-erbB-2) overexpression.

RESULTS: A statistically significant relationship was found regarding axillary lymph node involvement (p = 0.027), and oestrogen/progesterone receptor status (p = 0.013). No significant relationship was detected regarding other prognostic factors (p > 0.05).

CONCLUSION: Among various prognostic factors, ADC values were significantly correlated with only axillary lymph node positivity and oestrogen/progesterone receptor status.

ADVANCES IN KNOWLEDGE: In the present study, the relationship between ADC values of IDC lesions that are acquired at a high magnetic field (3.0 T) system by using multiple b-values and some specific prognostic factors that were not evaluated before in the medical literature was investigated.}, } @article {pmid26848801, year = {2016}, author = {Wobker, SE and Epstein, JI}, title = {Differential Diagnosis of Intraductal Lesions of the Prostate.}, journal = {The American journal of surgical pathology}, volume = {40}, number = {6}, pages = {e67-82}, doi = {10.1097/PAS.0000000000000609}, pmid = {26848801}, issn = {1532-0979}, mesh = {Carcinoma, Ductal/*diagnosis ; Diagnosis, Differential ; Humans ; Male ; Prostatic Intraepithelial Neoplasia/*diagnosis ; Prostatic Neoplasms/*diagnosis ; }, abstract = {The category of intraductal lesions of the prostate includes a range of primary prostatic and nonprostatic processes with wide variation in prognosis and recommended follow-up. Studies have shown that pathologists are uncomfortable with the diagnosis of these lesions and that the diagnostic reproducibility is low in this category. Despite the diagnostic difficulty, their accurate and reproducible diagnosis is critical for patient management. This review aims to highlight the diagnostic criteria, prognosis, and treatment implications of common intraductal lesions of the prostate. It focuses on the recognition of intraductal carcinoma of the prostate (IDC-P) in prostate needle biopsies and how to distinguish it from its common mimickers, including high-grade prostatic intraepithelial neoplasia, invasive cribriform prostatic adenocarcinoma, urothelial carcinoma extending into prostatic ducts, and prostatic ductal adenocarcinoma. IDC-P is independently associated with higher risk disease, and its identification in a needle biopsy, even in the absence of invasive carcinoma, should compel definitive treatment. Conversely, high-grade prostatic intraepithelial neoplasia has a much better prognosis and in limited quantities does not even warrant a repeat biopsy. IDC-P must be distinguished from urothelial carcinoma involving prostatic ducts, as recommended treatment varies markedly. Ductal adenocarcinoma may confuse the pathologist and clinician by overlapping terminology, and morphology may also mimic IDC-P on occasion. The use of ancillary testing with immunohistochemistry and molecular markers has also been reviewed.}, } @article {pmid26843058, year = {2016}, author = {Pare, R and Shin, JS and Lee, CS}, title = {Increased expression of senescence markers p14(ARF) and p16(INK4a) in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome.}, journal = {Histopathology}, volume = {69}, number = {3}, pages = {479-491}, doi = {10.1111/his.12948}, pmid = {26843058}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; *Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16/analysis/*biosynthesis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Tissue Array Analysis ; Tumor Suppressor Protein p14ARF/analysis/*biosynthesis ; }, abstract = {AIMS: Breast cancer is a hormonally driven disease. Cellular senescence is an age-related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) during breast cancer progression in a large patient cohort.

METHODS AND RESULTS: We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11-year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14(ARF) and p16(INK4a) but lower expression of p21(WAF1/Cip1) than non-malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) expression (P < 0.05). Univariate comparison showed a correlation between high p16(INK4a) expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14(ARF) expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16(INK4a) to be an important prognostic factor for overall survival (P = 0.011) and disease-free survival (P = 0.004), with p14(ARF) also being a significant prognostic factor for disease-free survival (P = 0.043). Moreover, patients showing both high p16(INK4a) expression and and high p14(ARF) expression had an adjusted three-fold increased risk of disease recurrence (P < 0.05) and a two-fold increased risk of all-cause-related death (P < 0.05).

CONCLUSIONS: These finding suggest p16(INK4a) expression and p14(ARF) expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors.}, } @article {pmid26839242, year = {2015}, author = {Romaniuk, A and Lyndin, M and Sikora, V and Lyndina, Y and Panasovska, K}, title = {Histological and immunohistochemical features of medullary breast cancer.}, journal = {Folia medica Cracoviensia}, volume = {55}, number = {2}, pages = {41-48}, pmid = {26839242}, issn = {0015-5616}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Medullary/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Disputes take place among many scientists about the position of MC in the classification of breast cancer. Some say that this kind of tumor is a sign of invasive ductal carcinoma (IDC). Instead, most of modern researchers distinguish MC of the breast as a separate nosological unit. Primarily there were selected 20 cases of MC and 10 cases of IDC (as control group). The immunohistochemical study revealed the presence of ER, PR, HER2/neo, p53, Ki-67, MMP1 and E-cadherin receptors. In the study of receptor status of tumors it was observed that 100% of MC cases were estrogen-, progesterone- and HER2/ neu negative. The status of tumors on receptor p53 and Ki-67 was as follows: p53+ status had 80% and Ki-67+ had 85% of tissues of MC. In 75% of cases MC cells expressed marker of adhesion and in 100% of cases cells were receptor-negative for expression of MMP1. The data of the study show that the invasive ductal carcinoma and medullary carcinoma are completely independent and different types of malignancy in the breast. The favorable behavior of medullary cancer is associated with expression of E-cadherin receptors, which are essentially adhesion factor and absence of MMP1 which are factors of metastatic potential of the tumor.}, } @article {pmid26838218, year = {2016}, author = {Moazzezy, N and Ebrahimi, F and Sisakht, MM and Yahyazadeh, H and Bouzari, S and Oloomi, M}, title = {Relationship between erb-B2 mRNA Expression in Blood and Tissue of Invasive Ductal Carcinoma Breast Cancer Patients and Clinicopathological Characteristics of the Tumors.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {17}, number = {1}, pages = {249-254}, doi = {10.7314/apjcp.2016.17.1.249}, pmid = {26838218}, issn = {2476-762X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/metabolism ; Breast Neoplasms/blood/*genetics/metabolism/*pathology ; Carcinoma, Ductal/blood/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Female ; Humans ; Lymph Nodes/metabolism/pathology ; Middle Aged ; Prognosis ; RNA, Messenger/blood/*genetics/metabolism ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb-B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC.}, } @article {pmid26837990, year = {2015}, author = {Thakur, NA and Humne, AY and Godale, LB}, title = {Delay in presentation to the hospital and factors affecting it in breast cancer patients attending tertiary care center in Central India.}, journal = {Indian journal of cancer}, volume = {52}, number = {1}, pages = {102-105}, doi = {10.4103/0019-509X.175602}, pmid = {26837990}, issn = {1998-4774}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Carcinoma, Medullary/diagnosis/*epidemiology/pathology ; *Early Detection of Cancer ; Female ; Hospitals ; Humans ; India ; Middle Aged ; Neoplasm Staging ; *Tertiary Care Centers ; }, abstract = {INTRODUCTION: Despite lower incidence of breast cancer in India, the total number of cases and the net mortality is high. To reduce this increasing load of mortality due to breast cancer we need to lay emphasis on early detection and increased use of systemic therapy. Early detection itself depends on early presentation to a health facility; thus, it is important to identify factors affecting delay in a presentation to hospital.

AIM AND OBJECTIVES: To study the clinico-social profile of breast carcinoma patients attending a tertiary care hospital and to study the time lag since detection of lump by women and presentation to the hospital and factors affecting them.

MATERIALS AND METHODS: A total of 120 primary breast cancer patients visiting a tertiary care hospital over a period of 7 months (August 2010 to February 2011) were taken up for study. A detailed retrospective analysis of patients was done according to planned proforma.

OBSERVATIONS: Maximum study subjects were in the age group of 41-50 years. Right and left breasts were equally affected. The most common histo-pathological type of breast carcinoma observed was invasive ductal carcinoma (NOS) in 105 (87.50%) cases. Majority of the cases were in stage III or stage II. The median time lag self-detection of lump in the breast by women and presentation to the hospital was 6 months. Women living in a rural area, those with lower socio-economic status and those with older age tend to assess health-care late.

CONCLUSIONS: Carcinoma of the breast is a common cancer affecting young to middle age group with invasive ductal carcinoma being the most common histological type. Delay in presentation and late stage presentation is a major concern. Hence, proper awareness and screening programmers are needed to identify, inform and educate these categories of women.}, } @article {pmid26834749, year = {2016}, author = {Rodrigues, CP and Ferreira, AC and Pinho, MP and de Moraes, CJ and Bergami-Santos, PC and Barbuto, JA}, title = {Tolerogenic IDO(+) Dendritic Cells Are Induced by PD-1-Expressing Mast Cells.}, journal = {Frontiers in immunology}, volume = {7}, number = {}, pages = {9}, pmid = {26834749}, issn = {1664-3224}, abstract = {Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen-presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3(+), secrete TGF-β and IL-10, and suppress the proliferation of mitogen-stimulated naïve T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression.}, } @article {pmid26832176, year = {2016}, author = {Karaarslan, S and Genç, B and Nart, A and Börekçi, İ and Buğdayci, MH}, title = {The Relation of Parafibromin Expression with Clinicopathological Factors in Invasive Breast Carcinomas.}, journal = {Turk patoloji dergisi}, volume = {32}, number = {1}, pages = {8-14}, doi = {10.5146/tjpath.2015.01342}, pmid = {26832176}, issn = {1309-5730}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Tumor Suppressor Proteins/analysis/*biosynthesis ; }, abstract = {OBJECTIVE: We aimed to find the relationship between parafibromin expression and clinicopathologic variables of breast carcinoma.

MATERIAL AND METHOD: Ninety-seven cases of invasive breast carcinoma diagnosed at our department between the years 2010-2013 were included in the study. The parafibromin expression state was compared with the estrogen receptor, progesterone receptor, cerbB2, Ki67 results, and the clinicopathological variables.

RESULTS: Among 97 breast carcinoma cases, 66 (68%) were invasive ductal carcinoma. The average age was 54.3 (min:25, max:100), and the average tumor size was 31.1 mm (min:7, max:120). Lymph node metastasis was detected in 58% of the cases. Eleven were diagnosed with metastasis amongst 77 cases whose distant metastasis data could be reached. Eleven cases were lost due to breast carcinoma. As the tumor grade increased, the possibility of distant metastasis and lymph node metastasis increased as well (p=0.04, p=0.05, respectively). The mean follow-up duration of the cases was 26.6 ± 9.8 (min. 6, max. 53) months, and there was no significant difference in survival between the other variables. Of the cases, 21.6% were negative, 9.3% were (+) positive, 11.3% were (++) positive and 57.7% were (+++) positive for parafibromin. It was found that there was an inverse correlation between the Ki67 proliferation index and lymph node metastasis and the parafibromin expression (p=0.018, p=0.029, respectively).

CONCLUSION: We suggest that parafibromin may be a possible prognostic and predictive parameter for breast carcinomas. As the data on this matter in the literature is limited, it would be beneficial to investigate the matter and evaluate its relationship with survival in larger series.}, } @article {pmid28492381, year = {2016}, author = {Hasenson-Atzmon, K and Marom, S and Sofer, T and Lev-Ari, L and Youngmann, R and Hermesh, H and Kushnir, J}, title = {Cultural Impact on SAD: Social Anxiety Disorder among Ethiopian and Former Soviet Union Immigrants to Israel, in Comparison to Native-born Israelis.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {53}, number = {3}, pages = {48-54}, pmid = {28492381}, issn = {2617-2402}, mesh = {Adolescent ; Adult ; Emigrants and Immigrants/*psychology ; Ethiopia/ethnology ; Female ; Humans ; Israel/ethnology ; Male ; Phobia, Social/*ethnology ; Students/*psychology ; USSR/ethnology ; Young Adult ; }, abstract = {BACKGROUND: Social Anxiety Disorder (SAD) is linked to social norms and role expectations which are culture dependent, such as the construal of one's self as independent or interdependent in relation to others. The current study is the first to examine SAD symptoms among Ethiopian and former Soviet Union immigrants to Israel compared to a sample of native Israelis. We investigated the relationship between SAD, ethnicity and independent/ interdependent self-construals.

METHODS: A total of 261 students (151 native-born Israelis, 60 Ethiopian immigrants and 50 students from the former USSR) were administrated the Liebowitz Scale (LSAS), the Self-construal Scale (SCS), Beck Depression Inventory (BDI) and a socio-demographic questionnaire.

RESULTS: Ethiopians exhibited highest SAD scores while no differences were found between the FSU immigrants and native-born Israelis. Additionally, Ethiopians and native-born Israeli students exhibited similar high interdependence scores. Finally, SAD scores were predicted by gender, origin, independent and interdependent self-construals.

CONCLUSION: Immigration per se is not a universal risk factor of SAD and ethnological-cultural factors do contribute specifically to SAD. A possible psychological mediator between culture and the susceptibility to SAD are the interdependence and independent self-construals. When treating immigrants, clinicians and health care providers are advised to consider the effect of cultural influence on the mental well-being and integration process of immigrants in to their host country.}, } @article {pmid28492379, year = {2016}, author = {Nakash, O and Nagar, M and Levav, I and Danilovich, E and Abu-Tair, M and Podolsky, G}, title = {Psychological Factors Associated with Emotional Distress among Palestinian Arabs from East Jerusalem Accessing Psychiatric Care in Israel.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {53}, number = {3}, pages = {33-38}, pmid = {28492379}, issn = {2617-2402}, mesh = {Adult ; Arabs/*psychology ; Female ; Humans ; Israel/ethnology ; Male ; Mental Disorders/*ethnology ; Mental Health Services ; Middle Aged ; Patient Acceptance of Health Care/*ethnology ; Prejudice/*ethnology ; *Social Support ; Stress, Psychological/*ethnology ; Young Adult ; }, abstract = {BACKGROUND: The Palestinian population residing in East Jerusalem is characterized by high rates of poverty and unemployment and is subject to discrimination in various forms, including infrastructure of mental health services. Little is known about the help seeking needs and practices of East Jerusalem residents.

METHOD: We examined socio-demographic and clinical characteristics of a consecutive sample Palestinian residents from East Jerusalem (N=50) who accessed a specially assigned psychiatric clinic in Israel. In addition, we examined the psychological factors associated with emotional distress among these service-users upon entry to care. Participants completed a survey in Arabic that included a socio-demographic questionnaire and measures assessing emotional distress, perceived exposure to discrimination and social support, and mental health stigma.

RESULTS: Participants reported high levels of emotional distress. Female gender, low socioeconomic status, higher perceived exposure to discrimination and higher perceived social support were associated with increased emotional distress.

CONCLUSIONS: Findings add to the scarce body of knowledge on specific mental health characteristics of East Jerusalem Palestinian residents.}, } @article {pmid28331756, year = {2016}, author = {Uslukaya, Ö and Gümüş, M and Gümüş, H and Bozdağ, Z and Türkoğlu, A}, title = {The Management and Outcomes of Male Breast Cancer.}, journal = {The journal of breast health}, volume = {12}, number = {4}, pages = {165-170}, pmid = {28331756}, issn = {1306-0945}, abstract = {OBJECTIVE: Due to a lack of sufficient data, the treatment protocols for male breast cancer are usually the same as those used for female breast cancer. The aim of the current study was to present our clinical experience with male breast cancer.

MATERIALS AND METHODS: The records of 37 patients who were treated for male breast cancer in our hospital between 2004 and 2014 were reviewed retrospectively. The data of patients were recorded and analyzed.

RESULTS: The mean age of the patients was 63.03±12.36 years. Thirty-three patients (89.2%) had invasive ductal carcinoma, two (5.4%) had ductal carcinoma in situ, and two had invasive lobular carcinoma (5.4%). The most common molecular subtype was luminal A (17 cases, 45.9%). Twenty-nine patients with male breast cancer underwent mastectomy and two underwent breast conserving surgery. Axillary lymph node dissection was performed in 25 patients. The most common surgical procedure was modified radical mastectomy. Distant metastases were present in 17 (45.9%) patients. Overall, the 5-year survival was 60%. The 5-year survival was 100% for those with stage 0-I disease, 87% for stage II, and 42% for stage III. The 3-year survival was 14% for stage IV.

CONCLUSION: Patients with male breast cancer presented at an older age, a later stage, and with earlier metastasis. Early metastasis and death increases with increasing stage. Poor prognosis correlates with late admission. Data from different centers should be compiled and reviewed in order to determine a specific treatment protocol for male breast cancer; each paper published reveals new data.}, } @article {pmid28331753, year = {2016}, author = {Arslan, M and Küçükerdem, HS and Can, H and Tarcan, E}, title = {Retrospective Analysis of Women with Only Mastalgia.}, journal = {The journal of breast health}, volume = {12}, number = {4}, pages = {151-154}, pmid = {28331753}, issn = {1306-0945}, abstract = {OBJECTIVE: Mastalgia is the most common symptom in women, who has gone under breast imaging. 70% of women face with mastalgia at least once in their lifetime. In our study, we aimed to investigate the examinations and the results of the females referred to our outpatient clinics with mastalgia and to determine the frequency of malignancy.

MATERIALS AND METHODS: Files of all women patients referred to General Surgery Outpatient Clinics between 01.06.2014-31.05.2015 has been investigated retrospectively. Cases only with breast pain complaint (n=789) out of 2798 women has been included in the study. Women with lump in breast, nipple discharge, redness, breast retraction and pregnant and lactating women were excluded. Breast examination findings, ultrasonography (USG), mammography results, whether biopsies are done or not and diagnoses have been investigated retrospectively.

RESULTS: Mean age was 42.97±12.36 (16-74) years. 59.7% (n=471) of the women had bilateral mastalgia and 91.1% (n=719) of the breast examinations were found to be normal. USG was required from 664 (84.2%) women and mammography was required from 448 (56.8%) women. Considering diagnoses; fibrocystic changes in 32.3% (n=201), ductal ectasia in 8.8% (n=55), fibroadenomas in 6.1% (n=38), reactive lymphoid hyperplasia in 1.1% (n=7) was observed. Only 1 (0.2%) woman was diagnosed with invasive ductal carcinoma.

CONCLUSION: According to researches, 0.5% of the women with mastalgia were diagnosed with breast cancer. In our study this rate was found as 0.2%. Women with only mastalgia without any abnormality in physical examination should be informed about dealing with pain.}, } @article {pmid28331748, year = {2016}, author = {Akın, Y and Uğurlu, MÜ and Kaya, H and Arıbal, E}, title = {Diagnostic Value of Diffusion-weighted Imaging and Apparent Diffusion Coefficient Values in the Differentiation of Breast Lesions, Histpathologic Subgroups and Correlatıon with Prognostıc Factors using 3.0 Tesla MR.}, journal = {The journal of breast health}, volume = {12}, number = {3}, pages = {123-132}, pmid = {28331748}, issn = {1306-0945}, abstract = {OBJECTIVE: The aim of this study was to evaluate the effect of the apparent diffusion coefficient (ADC) and diffusion-weighted imaging in differentiating benign from malignant breast lesions, histopathologic subtypes of breast tumors, and to find a correlation with prognostic factors using 3T MR.

MATERIALS AND METHODS: A total of 165 patients aged between 16 and 78 years with 181 histopathologically-verifed breast lesions were enrolled in this study. A 3T MR system and bilateral phased array breast coil was used. Diffusion-weighted imaging was performed with spin echo "echo planar" with "b" values: 50, 400, and 800 seconds/mm[2]. ADC values were calculated for normal fibroglandular tissue and breast lesions. ADC values of independent groups were compared using Student's t-test. ROC analysis was used to find a threshold ADC value in the differentiation of lesions.

RESULTS: The mean ADC values were 1.35±0.16 × 10[-3] mm[2]/s for normal fibroglandular tissue, 1.41±0.24 × 10[-3] mm[2]/s for benign breast lesions and 0.83±0.19 × 10[-3] mm[2]/s for malignant breast lesions. The AUC with ROC analysis was 0.945 and the threshold for ADC was 1.08 × 10[-3] mm[2]/s with a sensitivity and specificity of 92% and 92%, respectively. The threshold value for ADC ratio was 0.9 with 96% sensitivity and 89% specificity. The mean ADC of malignant breast lesions was statistically lower for benign lesions (p<0.01). We found no correlation between the mean ADC values and ER-PR receptor, Her2, and Ki-67 values.

CONCLUSION: Diffusion-weighted imaging has high diagnostic value with high sensitivity and specificity in differentiating malignant and benign breast lesions.}, } @article {pmid28331746, year = {2016}, author = {Uğurluer, G and Yavuz, S and Çalıkuşu, Z and Seyrek, E and Kibar, M and Serin, M and Ersöz, C and Demircan, O}, title = {Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer.}, journal = {The journal of breast health}, volume = {12}, number = {3}, pages = {112-118}, pmid = {28331746}, issn = {1306-0945}, abstract = {OBJECTIVE: In this study, we aimed to determine the correlation between pretreatment-staging 18F-FDG total body positron-emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) levels and histopathologic and immunohistochemical predictive and prognostic factors in patients with breast cancer.

MATERIALS AND METHODS: One hundred thirty-nine women with breast cancer who were treated between 2009 and 2015 at our hospital and who had pretreatment-staging PET/CT were included in the study. SUVmax levels and histopathologic and immunohistochemical results were compared.

RESULTS: The median age was 48 years (range, 29-79 years). The mean tumor diameter was 33.4 mm (range, 7-120 mm). The histology was invasive ductal carcinoma in 80.6% of the patients. In the univariate analysis, SUVmax levels were significantly higher in patients with invasive ductal carcinoma; in patients with a maximum tumor diameter more than 2 cm; patients who were estrogen, progesterone, and combined hormone receptor-negative, triple-negative patients, and in tumors with higher grades (p<0.05). In HER2-positive patients, SUVmax levels were higher even if it was not statistically significant. There was no correlation between lymph node metastases and pathologic stage. In multivariate analysis, tumor diameter was an independent factor.

CONCLUSION: SUVmax levels are correlated with known histopathologic and immunohistochemical prognostic factors. PET/CT could be useful in preoperative evaluation of patients with breast cancer to predict biologic characteristics of tumors and prognosis.}, } @article {pmid28331741, year = {2016}, author = {Çelebi, F and Köksal, Ü and Pilancı, KN and Ordu, Ç and Sarsenov, D and İlgün, S and Çabuk, FK and Alço, G and Özdil, G and Erdoğan, Z and Özmen, V}, title = {PET-MRI Findings of Two Patients with Breast Carcinoma before Treatment.}, journal = {The journal of breast health}, volume = {12}, number = {2}, pages = {88-90}, pmid = {28331741}, issn = {1306-0945}, abstract = {Integrated positron-emission tomography-magnetic resonance imaging (PET-MRI) is a new hybrid simultaneous imaging modality with higher soft tissue contrast and lower radiation doses compared with PET-CT. Two patients who were referred to our hospital with left breast masses that were pathologically diagnosed as invasive ductal carcinoma. The women were then scanned using the first PET-MRI system in Turkey, which was established in our department. In this case report, we aimed to determine the advantages of PET-MRI in staging, follow-up, neoadjuvant chemotherapy response, and to compare the usefulness of this modality with PET-CT and dynamic contrast-enhanced breast MRI.}, } @article {pmid28331739, year = {2016}, author = {Çabuk, FK and Aktepe, F and İlgün, AS and Sarsenov, D and Elbüken, F and Özmen, V}, title = {A Rare Tumor that Mimicked Metastasis in a Patient with Breast Cancer: Epithelioid Hemangioendothelioma.}, journal = {The journal of breast health}, volume = {12}, number = {2}, pages = {83-85}, pmid = {28331739}, issn = {1306-0945}, abstract = {A woman aged 50 years was diagnosed as having an invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast and underwent bilateral mastectomy eight years ago. A mass was identified during follow-up in positron-emission tomography (PET) image in the left infraclavicular region, indicating metastasis. Histopathologic examination showed a mass of 1.9 × 1 × 0.7 cm in dimensions characterized by spindle or round nuclei cells that formed island or cords in hyaline and myxoid ground and intracytoplasmic vacuoles containing erythrocytes. In the immunohistochemical analysis, tumor cells were widespread with diffuse positivity with CD34 and vimentin. These findings redirected us from a diagnosis of metastatic carcinoma to epithelioid hemangioendothelioma, a rare tumor of intermediate vascular tumor groups. In this respect, confirmation through biopsy from considered cases of metastasis is important in making a definite pathologic differential diagnosis.}, } @article {pmid28330128, year = {2016}, author = {Paryan, M and Tavakoli, R and Rad, SMAH and Feizi, N and Kamani, F and Mostafavi, E and Mohammadi-Yeganeh, S}, title = {Over-expression of NOTCH1 as a biomarker for invasive breast ductal carcinoma.}, journal = {3 Biotech}, volume = {6}, number = {1}, pages = {58}, pmid = {28330128}, issn = {2190-572X}, abstract = {Breast cancer is the leading cause of cancer-related death in women worldwide. Invasive ductal carcinoma (IDC) is the most frequent invasive form of breast cancer followed by metastasis. There is no accepted marker for distinguishing this form from other less aggressive forms of breast cancer. Therefore, finding new markers especially molecularly detectable ones are noteworthy. It has been shown that NOTCH1 has been overexpressed in the patients with breast cancer, but no study has investigated the expression of NOTCH1 and its correlation with other molecular and hormonal markers of breast cancer so far. In the current study, 20 breast cancer tissues and 20 matched adjacent normal breast tissue from breast cancer patients were obtained and categorized in two groups: patients with IDC and patient with other types of breast cancer. Gene expression analysis using real-time PCR showed that the NOTCH1 gene was significantly overexpressed in patients with IDC. We also found a slight correlation between NOTCH1 overexpression and p53 accumulation in the cancerous cells confirmed by Immunohistochemistry (IHC). This results showed that it is possible to introduce NOTCH1 expression as a novel biomarker of IDC, alone or preferably accompanied by IHC of p53. We also can design new therapeutic agents targeting NOTCH1 expression for inhibition of metastasis in ductal breast carcinoma.}, } @article {pmid29147419, year = {2015}, author = {Budimir, I and Sabol Pusic, M and Nikolic, M and Dorosulic, Z and Ljubicic, N and Stajduhar, E and Mise, I and Vazdar, L and Sarcevic, B}, title = {Obstructive Jaundice as an Uncommon Manifestation of Metastatic Breast Cancer.}, journal = {World journal of oncology}, volume = {6}, number = {1}, pages = {297-300}, pmid = {29147419}, issn = {1920-454X}, abstract = {Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient's long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.}, } @article {pmid28331721, year = {2015}, author = {Aydın, OU and Soylu, L and Ercan, Aİ and Bilezikçi, B and Koçak, S}, title = {Invasive Ductal Carcinoma Developing From Fibroadenoma.}, journal = {The journal of breast health}, volume = {11}, number = {4}, pages = {195-198}, pmid = {28331721}, issn = {1306-0945}, abstract = {Fibroadenomas are the most common benign breast lesions in adolescent and young women. It is most frequently observed in the 3rd decade. Although it is considered benign, evidence of malignant transformation is available. Cancer development may be from ground of fibroadenoma or near breast tissue. A case of a fibroadenoma coexisting with an invasive ductal carcinoma of the breast in a 31-year-old female is presented. The patient presented with the chief complaint of having a palpable mass in her right breast for the last 10 years. Mammography revealed a mass with microcalcifications. Core biopsy was performed, and the results indicated an invasive carcinoma. Breast-conserving surgery with sentinel lymph node biopsy was performed. The pathological features revealed a fibroadenoma coexisting with an invasive ductal carcinoma. This case suggests that clinicians and radiologists should always pay attention to the associated malignant imaging characteristics whenever a mass was followed up as fibroadenoma.}, } @article {pmid28331715, year = {2015}, author = {Poyraz, N and Emlik, GD and Keskin, S and Kalkan, H}, title = {Incidental Breast Lesions Detected on Computed Thorax Tomography.}, journal = {The journal of breast health}, volume = {11}, number = {4}, pages = {163-167}, pmid = {28331715}, issn = {1306-0945}, abstract = {OBJECTIVE: Although mammography is the primary imaging method of the breast, incidental benign and malignant breast lesions are increasingly being detected on computed tomographies (CTs) performed to detect different pathologies. Therefore, the detection and accurate identification of these lesions is important. In this study, we aimed to evaluate the frequency, morphological features, and results of incidental breast lesions on CTs performed for the detection of extramammarian pathologies.

MATERIALS AND METHODS: Incidental breast lesions on CTs performed in our department between 2011 and 2013 were evaluated. Patients who had previously diagnosed breast lesions were excluded from the study. The inclusion criteria were histopathologic diagnose and being followed-up for at least 2 years.

RESULTS: The study population consisted of 33 women whose mean age was 55±1.38 (37-78) years. Of the 33 women, 12 (36%) had malignant and 21 (64%) had benign or normal findings. The most common malignant lesion was invasive ductal carcinoma, and the most common benign lesion was fibroadenoma. Ill-defined contour and lymphadenopathy in malignant lesions and well-defined contour in benign lesions were the most important CT findings.

CONCLUSION: Breast must be carefully evaluated if it is included in the scans. An accurate report of breast lesions gives an opportunity for early diagnosis and treatment.}, } @article {pmid27386035, year = {2015}, author = {Adeniji-Sofoluwe, AT and Obajimi, GO and Obajimi, MO}, title = {Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.}, journal = {The Pan African medical journal}, volume = {20}, number = {}, pages = {239}, pmid = {27386035}, issn = {1937-8688}, mesh = {Adult ; Breast Diseases/diagnosis/*epidemiology/pathology ; Breast Feeding ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology ; Female ; Humans ; Lactation ; Nigeria/epidemiology ; Nipple Discharge ; Pregnancy ; Pregnancy Complications/diagnosis/*epidemiology/pathology ; Pregnancy Complications, Neoplastic/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Risk Factors ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6 ± 2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102 kg (mean 69.84 kg ± 15.33 SD). Their mean height was 159.8 cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to lactation.}, } @article {pmid27182510, year = {2014}, author = {Anele, AA and Bowling, M and Eckert, GJ and Gonzalez, E and Kipfer, H and Sauder, C}, title = {TREATMENT OF BREAST CANCER: IMO STATE NIGERIA VERSUS INDIANA, USA WOMEN - COMPARATIVE ANALYTIC STUDY.}, journal = {Journal of the West African College of Surgeons}, volume = {4}, number = {4}, pages = {39-69}, pmid = {27182510}, issn = {2276-6944}, abstract = {BACKGROUND: Women with breast cancer undergo multimodal treatment for best outcome. This study seeks to identify the treatment challenges for such women in Imo State, Nigeria vis-à-vis similar women in Indiana USA. We compared the treatment modalities of both groups; noting predictors of compliance for subsequent action.

SETTING: Federal Medical Centre, Owerri; Imo State, Imo State University, Orlu, Nigeria and Indiana University Hospital, Indiana, USA.

DESIGN: A retrospective study.

METHODOLOGY: From 2000-2013, 100 randomly pulled charts of patients treated for pathologically confirmed breast cancer in Imo, Nigeria Federal Medical Centre Owerri, Imo State University Hospital; and Indiana University Hospital U.S. respectively were reviewed. The demographics, clinical and pathological data of the patients with confirmed breast cancer were obtained. The data were formatted and analyzed with SPSS version 16.0. The clinical features, management options, outcomes and specific features were compared for both groups using Wilcoxon Rank Sum tests (age, parity) and chi-square tests for all other variables. A 5% significance level was used for all tests.

RESULTS: One hundred patients were included for each group. The mean/minimum ages; Imo, Nigeria 41.7/21 (SD/SE 15.3/1.5) vs. Indiana, U.S.56.4/29 (SD 12.4/SE 1.2) p<0.0001. Histology for Indiana USA women was predominantly ductal carcinoma in situ (DCIS) P<0.0001 while that of Imo, Nigeria was invasive ductal carcinoma inflammatory cancer P<0.0326. Women in both locations received chemotherapy and surgery. Imo women received less radiotherapy. Toxicity from chemotherapy remained constant features for both groups, P<0.0001. In Indiana USA, the 5year survival exceeded 85%; In Imo Nigeria it was 10%. This study showed that Women on both locations who were likely to be compliant were those receiving mastectomy; Imo, Nigeria 44(56%) <0.013 vs. Indiana, U.S. 74(80%) p<0.0186; women with cosmesis given; Imo, Nigeria 41(42%) vs. Indiana, U.S. 91 (94%) p<0.0001. Sample sizes were inadequate to perform multivariable models.

CONCLUSION: The multimodal treatment regimen implied that there was need for an algorithm protocol for breast cancer women. Thus the need to improve the quality of treatment particularly in Nigeria by improved treatment documentation to overcome key barriers involving information exchange.}, } @article {pmid28548069, year = {2014}, author = {Stripecke, R}, title = {Lentivirus-Induced Dendritic Cells (iDC) for Immune-Regenerative Therapies in Cancer and Stem Cell Transplantation.}, journal = {Biomedicines}, volume = {2}, number = {3}, pages = {229-246}, pmid = {28548069}, issn = {2227-9059}, abstract = {Conventional dendritic cells (cDC) are ex vivo differentiated professional antigen presenting cells capable of potently stimulating naïve T cells and with vast potential for immunotherapeutic applications. The manufacture of clinical-grade cDC is relatively complex and requires several days for completion. Clinical trials showed poor trafficking of cDC from subcutaneous injection sites to lymph nodes (LN), where DC can optimally stimulate naïve lymphocytes for long-lasting memory responses. We demonstrated in mouse and human systems that a single overnight ex vivo lentiviral (LV) gene transfer into DC precursors for production of combination of cytokines and antigens was capable to induce autonomous self-differentiation of antigen-loaded DC in vitro and in vivo. These highly viable induced DC (iDC) effectively migrated from the injected skin to LN, where they effectively activated de novo antigen-specific effector memory T cells. Two iDC modalities were validated in relevant animal models and are now in clinical development: Self-differentiated Myeloid-derived Antigen-presenting-cells Reactive against Tumors co-expressing GM-CSF/IL-4/TRP2 for melanoma immunotherapy in the autologous setting (SmartDCtrp2), and Self-differentiated Myeloid-derived Lentivirus-induced against human cytomegalovirus as an allogeneic matched adoptive cell after stem cell transplantation (SmyleDCpp65). The lentiviral vector design and packaging methodology has "evolved" continuously in order to simplify and optimize function and biosafety of in vitro and in vivo genetic reprogramming of iDC. Here, we address the challenges seeking for new creations of genetically programmed iDC and integrase-defective LV vaccines for immune regeneration.}, } @article {pmid28331673, year = {2014}, author = {Eralp, Y and Kılıç, L and Alço, G and Başaran, G and Doğan, M and Dinçol, D and Demirci, S and İçli, F and Onur, H and Saip, P and Haydaroğlu, A}, title = {The Outcome of Patients with Triple Negative Breast Cancer: The Turkish Oncology Group Experience.}, journal = {The journal of breast health}, volume = {10}, number = {4}, pages = {209-215}, pmid = {28331673}, issn = {1306-0945}, abstract = {OBJECTIVE: Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients from different centers in Turkey and identify clinical and pathologic variables that may effect survival.

MATERIALS AND METHODS: Between 1993-2007, from five different centers in Turkey, 316 nonmetastatic triple negative breast cancer patients were identified with follow-up of at least 12 months. The data was collected retrospectively from patient charts. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses.

RESULTS: Mean age at diagnosis was 49 years (range: 24-82). The majority of the patient group had invasive ductal carcinoma (n: 260, 82.3%) and stage II disease (n: 164; 51.9%). Majority of the patients (87.7%) received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84.6% and 71.6%, respectively. Univariate analysis revealed locally advanced disease (p: 0.001), advanced pathological stage (p: 0.021), larger tumor size (T1&T2 vs T3&T4) (p<0.001), nodal positivity (p: 0.006), and extensive nodal involvement (p<0.001) as significant factors for DFS; whereas, advanced pathological stage (p: 0.017), extensive nodal involvement (p<0.001) and larger tumor size (p: 0,001) and presence of breast cancer-affected member in the family (p=0.05) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed larger tumor size (T3&T4 vs T1&T2) and presence of lymph node metastases (node-positive vs node-negative) as significant independent prognostic factors for DFS (Hazard ratio (HR): 3.03, 95% CI: 1.71-5.35, p<0.001 and HR: 1.77, 95% CI: 1.05-3.0, p=0.03, respectively). Higher tumor stage was the only independent factor affecting overall survival (HR: 2.81; 95% CI, 1.27-6.22, p=0.01).

CONCLUSION: The outcome of patients with TNBC in this cohort is comparable to other studies including TNBC patients. Tumor size and presence of lymph node metastasis are the major independent factors that have effect on DFS, however higher tumor stage was the only negative prognostic factor for OS.}, } @article {pmid28331660, year = {2014}, author = {Yaðtu, M and Turan, E and Turan, ÇÖ}, title = {The Role of Ultrasographic Elastography in the Differential Diagnosis of Breast Masses and Its Contribution to Classical Ultrasonographic Evaluation.}, journal = {The journal of breast health}, volume = {10}, number = {3}, pages = {141-146}, pmid = {28331660}, issn = {1306-0945}, abstract = {OBJECTIVE: The aim of this study was to understand the role of ultrasonographic elastography method in the differentiation of breast masses and to assess its contribution to classic ultrasonographic evaluation.

MATERIALS AND METHODS: In this retrospective study, 76 breast masses in 76 patients were firstly evaluated by conventional ultrasonography (U.S.) and scored according to breast imaging report and data systems (BIRADS) and then evaluated with the Elastographic method during the same session between January and December 2013 in our hospital's Radiology Department. Findings were compared with pathological results. In statistical evaluation of the data, independent sample t tests were used for variables between groups.

RESULTS: The mean strain ratio of benign masses was 2.48±1.605 and strain score was 2.307±1.327. The mean strain ratio of malignant masses was 5.546±1.434 and strain score was 4.458±0.721. The most frequent benign masses were fibroadenoma and fibrocystic lesions. The most common malignant lesion was invasive ductal carcinoma. When the cut-off value for strain ratio was accepted as 4.009 in receiver operating curve (ROC) analysis for the differential diagnosis of malignant breast masses, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated as 83.8%, 76.9%, 62.3%, and 90.7%, respectively. When the limit value of strain patterns was accepted as scores 4 and 5, the sensitivity, specificity, PPV, and NPV were calculated as 42.7%, 94.2%, 77.2%, and 78%, respectively. When conventional ultrasonography (U.S.) findings were considered together with the elastographic strain ratios the sensitivity, specificity, PPV and NPV were 87.5%, 71.1%, 58.3% and 92.5%, respectively.

CONCLUSION: Elastography is not a method that can replace conventional breast ultrasound for detecting breast cancer, however it may be an adjunct to conventional ultrasound by increasing its diagnostic power.}, } @article {pmid29147332, year = {2013}, author = {Tural, D and Akar, E and Sager, S and Yildiz, O and Ozguroglu, M}, title = {A Case of Complete Response to Letrozol Treatment in a Postmenopausal Woman With Breast Cancer Who has Progressed After Multiple Lines of Chemotherapy.}, journal = {World journal of oncology}, volume = {4}, number = {1}, pages = {58-60}, pmid = {29147332}, issn = {1920-454X}, abstract = {Approximately 60% of all breast cancers are endocrine dependent. Postmenopausal patients who have positive hormone receptor status are eligible for aromatase inhibitor treatment. Letrozole is a potent, selective, non-steroidal, third-generation aromatase inhibitor which reduces oestrogen biosynthesis approximately 99% at the dose of 2.5 mg/day. We report a 54-years-old female patient diagnosed with grade 2 invasive ductal carcinoma of the breast. She received adjuvant chemotherapy, followed by 5 years of tamoxifen. After 8 years, recurrence appeared in lung, supraclavicular lymph nodes and brain. She had many cycles of cytotoxic chemotherapeutic agents, trastuzumab and lapatinib previously. After the progression (lung and brain), palliative therapy was thought due to very poor performance status of the patient. (ECOG: 3) Letrozole was added in the treatment and we obtained near-complete remission from her lung and brain metastasis with 2.5 mg/day dose of letrozole. This study might support successfully use of aromatase inhibitors in patients who has been previously treated with multiple lines of chemotherapy and had still progressive disease.}, } @article {pmid26838504, year = {2012}, author = {Brachtel, E}, title = {Molecular Pathology of the Breast.}, journal = {Surgical pathology clinics}, volume = {5}, number = {4}, pages = {793-819}, doi = {10.1016/j.path.2012.08.001}, pmid = {26838504}, issn = {1875-9181}, abstract = {Information focuses on molecular pathology of breast cancer. Presented are clinical features of breast cancer, detailed discussion of histology and molecular pathology for invasive ductal carcinoma, invasive lobular carcinoma, other subtypes of invasive breast cancer, and breast cancer progression and precursors. Phenotypes and genotypes of breast cancer are presented, along with the role of biomarkers, gene profiling, and hormone receptors. Targeted therapies and prognostic indicators are presented with practical applications of molecular pathology for the surgical pathologist.}, } @article {pmid28519509, year = {2012}, author = {Jacobs, MA}, title = {SU-E-I-24: Determining the Optimal B-Values to Use in Diffusion Weighted Imaging for Differentiating Benign and Malignant Breast Lesions.}, journal = {Medical physics}, volume = {39}, number = {6Part4}, pages = {3630}, doi = {10.1118/1.4734739}, pmid = {28519509}, issn = {2473-4209}, abstract = {PURPOSE: To investigate and determine the optimal b-values for Diffusion Weighted Imaging(DWI) for Apparent Diffusion Coefficient(ADC) maps in differentiating normal, benign and malignant breast tissue.

METHODS: Twenty-five patients underwent diffusion-weighted magnetic resonance imaging (DWI-MRI) and conventional breast MRI with suspicious breast fmdings(BIRADS >4). Breast lesions were defined by pathology. The DWI was acquired with different b-values ranging from 0,500, 600,750 and 1000s/mm[2] . Apparent Diffusion Coefficient(ADC) maps of breast tissue were constructed using different b-values, e.g., using either 2 b-values(0- 1000) or combinations of 3 or more (0,500,1000 or 0,600,750,1000). Quantitative analyses of the ADC maps of glandular, fatty and lesion tissue were obtained. Ratios of lesion to glandular tissue(L/GT) and signal to noise(SNR) were assessed. Paired t-tests were performed for statistical significance.

RESULTS: Eighteen patients had invasive ductal carcinoma and 7 had benign breast lesions. The mean ADC value for malignant lesions using all b values was 1.17±0.16×10-3mm[2] /s with a lesion to glandular(L/GT) ratio=0.65. The benign lesions, ADC map value was 1.86±0.03×10-3mm[2] /s with L/GT=0.98. There was a significant difference(P<0.05) between benign and malignant lesions ADC map value.The lowest SNR(12±6) was with single b-values. There was a significant difference(P<0.05) in SNR with multiple b-values(34±6) compared to single b-values. The highest SNR was given by using two b values greater than 500. Finally, the background noise for all combinations was surprising stable and ranged between 60±20%.

CONCLUSIONS: This is the first study to investigate the effect of changing different b values in DWI breast imaging. There were significant differences in the SNR between single and multiple b values. Our data show suggest that the recommended b-values for DWI in breast are 0, and two that are 500 or greater. Therefore use of at least 3 b-values in DWI/ADC mapping of breast lesions are needed for better characterization of benign and malignant breast tissue. P50CA88843, Avon Foundation for Women:01-2008-012, U01CA070095, andU01CA140204.}, } @article {pmid27330595, year = {2012}, author = {Yang, L and Park, JM and Askeland, RW and Fajardo, LL}, title = {Necrotizing granulomatous inflammation in an ipsilateral axillary lymph node in a patient with invasive ductal carcinoma of the breast.}, journal = {Radiology case reports}, volume = {7}, number = {4}, pages = {738}, pmid = {27330595}, issn = {1930-0433}, abstract = {A patient presented with flu-like symptoms and a warm, tender area in the left axilla after working with an ancient piece of Cyprus wood. Antibiotics prescribed failed to improve symptoms. Followup physical examination and subsequent ultrasound found suspicious left-breast mass and an enlarged lymph node in the left axilla. Biopsy and lumpectomy of the left-breast mass revealed invasive ductal carcinoma. Biopsy and excision of the enlarged lymph node in the left axilla revealed necrotizing granulomatous inflammation without evidence of metastatic breast carcinoma. To our knowledge, this is the first case report to show the coexistence of breast cancer with necrotizing granulomatous inflammation in the ipsilateral axillary lymph node, likely due to exposure to ancient wood.}, } @article {pmid29147190, year = {2010}, author = {Cintra, KA and Mattar, A and Joo, YK and Melitto, A and Gonzales, R and Nonogaki, S and Soares, FA and Logullo, AF and Gebrim, LH}, title = {Correlation Between Anthropometric Measures and Biomarker Changes After Neoadjuvant Therapy With Tamoxifen or Anastrozole in Postmenopausal Women With Breast Cancer.}, journal = {World journal of oncology}, volume = {1}, number = {3}, pages = {111-117}, pmid = {29147190}, issn = {1920-454X}, abstract = {BACKGROUND: Epidemiological studies have reported positive associations between anthropometric measures and risk for developing breast cancers that express hormone receptors and associated mortality. However, the impact of nutritional status on the molecular response to endocrine therapy has yet to be described.

METHODS: Body mass index (BMI), waist circumference (WC), hip circumference (HP), and waist-to-hip ratio (WHR) were measured in patients with invasive ductal carcinoma (IDC) before and after neoadjuvant treatment with either tamoxifen or anastrozole, and a possible correlation with prognostic factors, as estrogen receptor (ER), progesterone receptor (PgR), and proliferative index (Ki-67), was analyzed. Fifty-seven patients with palpable ER-positive IDC were randomized into three neoadjuvant treatment groups and received anastrozole or placebo or tamoxifen for twenty-one days. Biomarker status was obtained by comparing the immunohistochemical evaluation of samples collected before and after treatment, using the Allred scoring system. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS).

RESULTS AND CONCLUSIONS: After treatment, the anastrozole group showed reduced ER and PgR expression (p < 0.05), and both the anastrozole and tamoxifen groups showed lower Ki-67 status. A significant reduction in PgR positivity (p < 0.05) was found in women with large WC and HC who were treated with anastrozole. Reduction in PgR positivity also tended to be associated with BMI (p = 0.09) in the anastrozole group. BMI, WC, HC and WHR correlated neither with biomarker levels in the tamoxifen and placebo groups nor with ER and Ki-67 status in the anastrozole group after primary endocrine treatment.}, } @article {pmid29147178, year = {2010}, author = {Trabelsi, A and Abdelkrim, SB and Stita, W and Boudagga, MZ and Hammedi, F and Mokni, M}, title = {In Situ and Invasive Ductal Carcinoma Within a Borderline Phyllodes Tumor.}, journal = {World journal of oncology}, volume = {1}, number = {1}, pages = {42-44}, pmid = {29147178}, issn = {1920-454X}, abstract = {A rare case of a borderline phyllodes tumor with simultaneous intraductal and infiltrating duct carcinoma is reported. The patient was a 52-year-old woman with a breast tumor detected by physical examination. A simple mastectomy was performed. The excised tumor had a macroscopic appearance of a phyllodes tumor. After histological examination, the diagnosis of ductal carcinoma within a borderline phyllodes tumor was made. Immunohistochemical staining revealed that the epithelial component was positive for Epithelial Membrane Antigen and cytokeratin. No metastasis was detected in the axillary lymph nodes and the patient didn't receive any adjuvant therapy. No recurrence or metastasis has been observed 38 months after the surgery.}, } @article {pmid27307845, year = {2010}, author = {Voria, P and Eby, PR and Allison, K}, title = {Primary breast lymphoma.}, journal = {Radiology case reports}, volume = {5}, number = {1}, pages = {351}, pmid = {27307845}, issn = {1930-0433}, abstract = {We report a case of primary breast lymphoma in a 75-year-old woman who noticed a lump in her right breast after trauma. Mammographic, ultrasonographic, and pathologic correlations are provided. The typical appearance of primary breast lymphoma on mammography is a solitary, uncalcified, circumscribed, or indistinctly marginated mass with adjacent lymphadenopathy. On ultrasound, primary breast lymphoma is usually hypoechoic with circumscribed or microlobulated margins demonstrating increased vascularity. The differential diagnosis for a mass with this appearance is discussed in detail and includes hematoma, abscess, primary breast lymphoma, invasive ductal carcinoma, phyllodes tumor, and metastatic disease.}, } @article {pmid26837902, year = {2008}, author = {Zhou, M and Magi-Galluzzi, C}, title = {Prostatic Adenocarcinoma, Prostatic Intraepithelial Neoplasia, and Intraductal Carcinoma.}, journal = {Surgical pathology clinics}, volume = {1}, number = {1}, pages = {43-75}, doi = {10.1016/j.path.2008.08.001}, pmid = {26837902}, issn = {1875-9181}, abstract = {Prostate carcinoma (PCa) exhibits a wide range of architectural and cytological features. Gleason grading remains as one of the most powerful histological prognostic parameters. However, it has evolved considerably. High-grade prostatic intraepithelial neoplasia (high-grade PIN) is accepted as a precursor lesion to PCa. Its detection in prostate biopsy is also considered as a risk factor for detecting cancer in subsequent biopsies. Such risk, however, has significantly decreased in recent studies. Intraductal carcinoma of the prostate (IDC-P) represents the intraductal spread of invasive cancer and constitutes a poor histologic parameter. This article reviews the key histological features of PCa, high-grade PIN and IDC-P, as well as the Gleason grading system that was most recently updated in 2005.}, } @article {pmid26642960, year = {2016}, author = {Endo, Y and Dong, Y and Kondo, N and Yoshimoto, N and Asano, T and Hato, Y and Nishimoto, M and Kato, H and Takahashi, S and Nakanishi, R and Toyama, T}, title = {HER2 mutation status in Japanese HER2-positive breast cancer patients.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {6}, pages = {902-907}, doi = {10.1007/s12282-015-0659-y}, pmid = {26642960}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Asian People/genetics ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Female ; Humans ; Middle Aged ; *Mutation ; Receptor, ErbB-2/antagonists & inhibitors/*genetics/metabolism ; Trastuzumab/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.

METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.

RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.

CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.}, } @article {pmid26829374, year = {2016}, author = {Annacontini, L and Ciancio, F and Parisi, D and Innocenti, A and Portincasa, A}, title = {Management of nipple-areolar complex complications in skin-sparing mastectomy with prosthetic reconstruction A case report.}, journal = {Annali italiani di chirurgia}, volume = {87}, number = {ePub}, pages = {}, pmid = {26829374}, issn = {2239-253X}, mesh = {Breast Neoplasms/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Female ; Humans ; Mammaplasty/*adverse effects/methods ; *Mastectomy, Subcutaneous/adverse effects/methods ; Middle Aged ; *Negative-Pressure Wound Therapy/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Nipples/*blood supply ; Prostheses and Implants ; Surgical Wound/*etiology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION AND OBJECCTIVES: Venous congestion of the NAC (Nipple-Areola Complex) is not an uncommon complication of Skin-Reducing Mastectomy (SRM). The correct and prompt evaluation of the NAC's vitality in the first hours after surgery is important for the survival of the same, in fact the possibility of early intervention allows avoiding the use of invasive and radicals techniques to the advantage of simpler rapid procedures.

MATERIALS AND METHODS: DM, 57yr, multiple invasive ductal carcinoma of the right breast, underwent a SRM and immediate reconstruction with implant in August 2014 In the immediate post-operative appeared a venous stasis of the NAC. Treatment started with Negative Pressure Wound Therapy (NWPT) through VAC-Systems to 75 mmHg.

RESULTS: The use of the VAC-Therapy was in total 12 days and allowed the partial rescue of the NAC (85%). the vacuum pump is put into a portable bag so the patient's mobility is not limited.

DISCUSSION: NWPT permitted a rapid resolution of NAC's complication in SRM in order to guarantee an optimal timing for the start of adjuvant chemotherapy. The VAC-Therapy is a cost effective and simple to use in cases of suffering venous NAC in patients undergoing breast surgery.

KEY WORDS: NAC, NWPT, Skin-Reducing Mastectomy, VAC-Therapy.}, } @article {pmid26826418, year = {2016}, author = {Mardekian, SK and Bombonati, A and Palazzo, JP}, title = {Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.}, journal = {Human pathology}, volume = {49}, number = {}, pages = {114-123}, doi = {10.1016/j.humpath.2015.11.003}, pmid = {26826418}, issn = {1532-8392}, mesh = {Animals ; Biomarkers, Tumor/analysis/*genetics ; Biopsy ; Breast Neoplasms/chemistry/*genetics/pathology/therapy ; Carcinoma/chemistry/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*genetics/pathology/therapy ; Disease Progression ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Mastectomy ; Molecular Diagnostic Techniques ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Reproducibility of Results ; Treatment Outcome ; }, abstract = {Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance.}, } @article {pmid26823905, year = {2015}, author = {Huo, Z and Gao, Y and Yu, Z and Zuo, W and Zhang, Y}, title = {Metastasis of breast cancer to renal cancer: report of a rare case.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {11}, pages = {15417-15421}, pmid = {26823905}, issn = {1936-2625}, mesh = {Adult ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Carcinoma, Renal Cell/chemistry/*pathology ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Kidney Neoplasms/chemistry/*pathology/secondary ; Mastectomy, Modified Radical ; Neoplasms, Multiple Primary/chemistry/*pathology/surgery ; Nephrectomy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.}, } @article {pmid26823849, year = {2015}, author = {Liu, GX and Yu, YC and He, XP and Ren, SN and Fang, XD and Liu, F and He, Y}, title = {Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {11}, pages = {15093-15099}, pmid = {26823849}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/*pathology ; Cross-Sectional Studies ; Ether-A-Go-Go Potassium Channels/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Triple Negative Breast Neoplasms/*pathology ; }, abstract = {BACKGROUNDS: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer.

MATERIALS AND METHODS: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruited. We investigated the association of the Eag1 with clinicopathological features and molecular subtype of in triple negative breast cancer (TNBC) by univariate or multivariate analysis in a cross-section study.

RESULTS: The positive rate of Eag1 was 18.5% higher in TNBC compared with non-triple negative breast cancer (Non-TNBC) (P = 0.012, OR = 2.83, 95% CI = 2.16-3.47). Compared with the Eag1 negative group, the expression of Eag1 was linked to the larger tumor size (P = 0.002), advanced TNM stage (P = 0.029), high proportion of positive lymph node (87.6% vs. 65%, P = 0.014) and invasive ductal carcinoma (91% vs. 75%, P = 0.046).

CONCLUSIONS: The expression of Eag1 may be partially explained the aggressive behavior of TNBC in the breast cancer tissue.}, } @article {pmid26819702, year = {2016}, author = {Fu, SW and Lee, W and Coffey, C and Lean, A and Wu, X and Tan, X and Man, YG and Brem, RF}, title = {miRNAs as potential biomarkers in early breast cancer detection following mammography.}, journal = {Cell & bioscience}, volume = {6}, number = {}, pages = {6}, pmid = {26819702}, issn = {2045-3701}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; }, abstract = {Breast cancer is the most common cancer among American women, except for skin cancers. About 12 % women in the United States will develop invasive breast cancer during their lifetime. Currently one of the most accepted model/theories is that ductal breast cancer (most common type of breast cancer) follows a linear progression: from normal breast epithelial cells to ductal hyperplasia to atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), and finally to invasive ductal carcinoma (IDC). Distinguishing pure ADH diagnosis from DCIS and/or IDC on mammography, and even combined with follow-up core needle biopsy (CNB) is still a challenge. Therefore subsequent surgical excision cannot be avoided to make a definitive diagnosis. MicroRNAs (miRNAs) are a highly abundant class of endogenous non-coding RNAs, which contribute to cancer initiation and progression, and are differentially expressed between normal and cancer tissues. They can function as either tumor suppressors or oncogenes. With accumulating evidence of the role of miRNAs in breast cancer progression, including our own studies, we sought to summarize the nature of early breast lesions and the potential use of miRNA molecules as biomarkers in early breast cancer detection. In particular, miRNA biomarkers may potentially serve as a companion tool following mammography screening and CNB. In the long-term, a better understanding of the molecular mechanisms underlying the miRNA signatures associated with breast cancer development could potentially result in the development of novel strategies for disease prevention and therapy.}, } @article {pmid26817878, year = {2016}, author = {Ko, ES and Kim, JH and Lim, Y and Han, BK and Cho, EY and Nam, SJ}, title = {Assessment of Invasive Breast Cancer Heterogeneity Using Whole-Tumor Magnetic Resonance Imaging Texture Analysis: Correlations With Detailed Pathological Findings.}, journal = {Medicine}, volume = {95}, number = {3}, pages = {e2453}, pmid = {26817878}, issn = {1536-5964}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Contrast Media ; Female ; Humans ; Image Enhancement ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {There is no study that investigates the potential correlation between the heterogeneity obtained from texture analysis of medical images and the heterogeneity observed from histopathological findings. We investigated whether texture analysis of magnetic resonance images correlates with histopathological findings.Seventy-five patients with estrogen receptor positive invasive ductal carcinoma who underwent preoperative breast magnetic resonance imaging (MRI) were included. Tumor entropy and uniformity were determined on T2- and contrast-enhanced T1-weighted subtraction images under different filter levels. Two pathologists evaluated the detailed histopathological findings of the tumors including tumor cellularity, dominant stroma type, central scar, histologic grade, extensive intraductal component (EIC), and lymphovascular invasion. Entropy and uniformity values on both T2- and contrast-enhanced T1-weighted subtraction images were compared with detailed pathological findings.In a multivariate analysis, entropy significantly increased only on unfiltered T2-weighted images (P = 0.013). Tumor cellularity and predominant stroma did not affect the uniformity or entropy on both T2- and contrast-enhanced T1-weighted subtraction images. High histologic grades showed increased uniformity and decreased entropy on contrast-enhanced T1-weighted subtraction images, whereas the opposite tendency was observed on T2-weighted images. Invasive ductal carcinoma with an EIC or lymphovascular invasion only affected the contrast-enhanced T1-weighted subtraction images, through increased uniformity and decreased entropy. The best uniformity results were recorded on T2- and contrast-enhanced T1-weighted subtraction images at a filter level of 0.5. Entropy showed the best results at a filter level of 0.5 on contrast-enhanced T1-weighted subtraction images. However, on T2-weighted images, an ideal model was achieved on unfiltered images.MRI texture analysis correlated with pathological tumor heterogeneity.}, } @article {pmid26813772, year = {2016}, author = {Saita, C and Goto, R and Aruga, T and Idera, N and Honda, Y and Horiguchi, K and Miyamoto, H and Horiguchi, S and Yamashita, T and Kuroi, K}, title = {Invasive papillary carcinoma treated with neoadjuvant endocrine therapy in which pathological complete response was achieved.}, journal = {BMC research notes}, volume = {9}, number = {}, pages = {46}, pmid = {26813772}, issn = {1756-0500}, mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/genetics/metabolism/pathology/*therapy ; Carcinoma, Papillary/genetics/metabolism/pathology/*therapy ; Female ; Gene Expression ; Humans ; Letrozole ; Neoadjuvant Therapy/methods ; Nitriles/*therapeutic use ; Postmenopause ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Treatment Outcome ; Triazoles/*therapeutic use ; }, abstract = {BACKGROUND: Invasive papillary carcinoma is a rare type of invasive ductal carcinoma. Neoadjuvant endocrine therapy is now considered as an optional therapy for postmenopausal women with hormone receptor-positive breast cancers, including invasive papillary carcinoma.

CASE PRESENTATION: We discuss the case of an 83-year-old postmenopausal Japanese female with hormone receptor-positive invasive papillary carcinoma who started treatment with an aromatase inhibitor and achieved pathological complete response after 12 months of endocrine treatment.

CONCLUSION: Appropriate drugs and durations of neoadjuvant endocrine treatment have yet to be established. Continuing therapy with an aromatase inhibitor until the best clinical response is achieved may represent one of the best strategies in neoadjuvant endocrine therapy.}, } @article {pmid26807730, year = {2016}, author = {Korsten, H and Ziel-van der Made, AC and van Weerden, WM and van der Kwast, T and Trapman, J and Van Duijn, PW}, title = {Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.}, journal = {PloS one}, volume = {11}, number = {1}, pages = {e0147500}, pmid = {26807730}, issn = {1932-6203}, mesh = {Adenocarcinoma/chemistry/genetics/pathology ; Animals ; Apoptosis/genetics ; Biomarkers ; Biomarkers, Tumor ; Cadherins/analysis ; Carcinoma/chemistry/*genetics/pathology ; Carcinosarcoma/chemistry/genetics/pathology ; Cellular Senescence/genetics ; Disease Progression ; Epithelial Cells/chemistry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Inflammation/genetics ; Keratins/analysis ; Male ; Mesoderm/chemistry ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Neoplasm Proteins/analysis ; Neovascularization, Pathologic/genetics/pathology ; PTEN Phosphohydrolase/*deficiency ; Prostatic Hyperplasia/genetics/pathology ; Prostatic Neoplasms/chemistry/classification/*genetics/pathology ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/genetics ; Stromal Cells/chemistry ; }, abstract = {Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model. The morphologies of the tumors that developed were very heterogeneous. Different histopathological growth patterns could be identified, including intraductal carcinoma (IDC), adenocarcinoma and undifferentiated carcinoma, all strongly positive for the epithelial cell marker Cytokeratin (CK), and carcinosarcomas, which were negative for CK. IDC pattern was already detected in prostates of 7-8 month old mice, indicating that it could be a precursor stage. At more than 10 months IDC and carcinosarcoma were most frequently observed. Gene expression profiling discriminated essentially two molecular subtypes, denoted tumor class 1 (TC1) and tumor class 2 (TC2). TC1 tumors were characterized by high expression of epithelial markers like Cytokeratin 8 and E-Cadherin whereas TC2 tumors showed high expression of mesenchyme/stroma markers such as Snail and Fibronectin. These molecular subtypes corresponded with histological growth patterns: where TC1 tumors mainly represented adenocarcinoma/intraductal carcinoma, in TC2 tumors carcinosarcoma was the dominant growth pattern. Further molecular characterization of the prostate tumors revealed an increased expression of genes associated with the inflammatory response. Moreover, functional markers for senescence, proliferation, angiogenesis and apoptosis were higher expressed in tumors compared to hyperplasia. The highest expression of proliferation and angiogenesis markers was detected in TC2 tumors. Our data clearly showed that in the genetically well-defined PSA-Cre;Pten-loxP/loxP prostate tumor model, histopathological, molecular and biological heterogeneity occurred during later stages of tumor development.}, } @article {pmid26805362, year = {2015}, author = {Ebihara, T and Yamamoto, T and Hoshino, H and Yoshimura, J and Sasamatsu, S and Hiraki, Y and Nishi, H and Shimizu, K and Kawada, M and Inoue, T and Kato, F and Amano, K and Mikami, J and Yamamura, J and Makari, Y and Nakata, K and Ikeda, N and Kamigaki, S and Tsujie, M and Kimura, Y and Nakata, Y and Munakata, S and Ohzato, H}, title = {[A Case of Invasive Ductal Carcinoma in the Fat Replacement of the Pancreatic Body and Tail].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {2354-2356}, pmid = {26805362}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy/*surgery ; Chemotherapy, Adjuvant ; Deoxycytidine/analogs & derivatives/therapeutic use ; Fats/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Pancreas/pathology/*surgery ; Pancreatectomy ; Pancreatic Neoplasms/drug therapy/pathology/*surgery ; Splenectomy ; Gemcitabine ; }, abstract = {A 56 year-old woman with obesity (BMI3 2) and diabetes mellitus was diagnosed with right renal cell carcinoma. She underwent right nephrectomy 1 year ago. Seven months after surgery, CT revealed a rapidly growing mass near the spleen. The mass showed slight accumulation of FDG (SUVmax=2.4) on PET-CT. Since the lesion grew rapidly and was not enhanced in the early phase of enhanced CT, we diagnosed pancreatic cancer. Distal pancreatectomy and splenectomy were performed. The final pathological diagnosis was invasive ductal carcinoma in the fat replacement of the pancreatic body and tail. Postoperatively, the patient had no complications such as pancreatic fistula or aggravation of glucose intolerance. She received postoperative chemotherapy with gemcitabine. Since she developed pulmonary artery thrombosis, postoperative chemotherapy was interrupted after 8 courses. Thirty-two months after the surgery, she was still living without any recurrence. Acinar cells were absent in the fat replacement of the pancreas, but the pancreatic duct cells were still present. There was carcinoma in situ in the main pancreatic duct surrounding chronic inflammation. Fat replacement itself could be potentially precursor of the pancreatic cancer.}, } @article {pmid26805359, year = {2015}, author = {Noguchi, K and Tomimaru, Y and Eguchi, H and Ogawa, H and Yamada, D and Tomokuni, A and Noda, T and Asaoka, T and Wada, H and Kawamoto, K and Goto, K and Marubashi, S and Nagano, H and Mori, M and Doki, Y}, title = {[Three Resected Cases of Metachronous Pancreatic Cancer Successfully Treated with Repeated Pancreatectomy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {2346-2348}, pmid = {26805359}, issn = {0385-0684}, mesh = {Aged ; Biopsy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/drug therapy/secondary ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Recurrence ; }, abstract = {Repeated pancreatectomy for metachronous pancreatic cancer has rarely been reported. We report 3 cases with metachronous pancreatic ductal carcinoma that developed after pancreatectomy for the first pancreatic cancer. They were successfully resected by removal of the remnant pancreas. In all 3 cases, the cancers in the remnant pancreas were treated with repeated pancreatectomy. The histological margin of the first pancreatic resection was cancer-free in all the cases. Furthermore, the second cancer tissue contained carcinoma lesions in situ adjacent to invasive ductal carcinoma. Based on these findings, the 3 patients were diagnosed with metachronous pancreatic cancers.}, } @article {pmid26805181, year = {2015}, author = {Aomatsu, N and Tei, S and Haraoka, G and Hosoi, K and Fujii, N and Tsujio, G and Hiramatsu, S and Wang, E and Iwauchi, T and Morimoto, J and Nishii, T and Kosaka, K and Uchima, Y and Takeuchi, K}, title = {[A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1812-1814}, pmid = {26805181}, issn = {0385-0684}, mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy, Large-Core Needle ; Breast Implants ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Nitriles/therapeutic use ; Tissue Expansion Devices ; Triazoles/therapeutic use ; }, abstract = {We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.}, } @article {pmid26805179, year = {2015}, author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Murata, T and Okuno, K and Hoshino, M and Matsuyama, T and Goto, H and Koshiishi, H and Yoshimura, T and Osanai, T and Suzuki, K}, title = {[Subclavian Artery Hemorrhage Related to Everolimus in a Patient with Recurrent Breast Cancer--A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1806-1808}, pmid = {26805179}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Everolimus/administration & dosage/*adverse effects ; Fatal Outcome ; Female ; Hemorrhage/*chemically induced ; Humans ; Mastectomy, Segmental ; Middle Aged ; Recurrence ; *Subclavian Artery ; }, abstract = {A 53-year-old woman underwent breast-conserving surgery for right breast cancer (invasive ductal carcinoma, T1cN0M0, ly+, stage ⅠA, ER+, PR+, HER2-) 5 years previously. During treatment with tamoxifen, massive recurrence in the axillary lymph nodes was found. First- through fourth-line chemotherapy were tried, but they all failed. Everolimus and exemestane were administered, resulting in rapid shrinking of the tumor, but the patient developed sudden severe bleeding from the subclavian artery. Hemostasis was achieved with artery stenting. The patient also developed a thoracic duct-cutaneous fistula. The patient died from tumor regrowth 6.5 months after her first everolimus treatment. Treating tumors involving major vessels with everolimus can cause severe bleeding after rapid shrinking of the tumor.}, } @article {pmid26805177, year = {2015}, author = {Asano, Y and Kashiwagi, S and Goto, W and Kurata, K and Morisaki, T and Noda, S and Takashima, T and Onoda, N and Ohsawa, M and Hirakawa, K}, title = {[A Case of Spontaneous Regression of Breast Cancer with Multiple Lung Metastases].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1800-1802}, pmid = {26805177}, issn = {0385-0684}, mesh = {Aged ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; *Neoplasm Regression, Spontaneous ; Silicates/therapeutic use ; Titanium/therapeutic use ; }, abstract = {Spontaneous regression of any malignant tumor is a rare event, occurring in about 1 of 60,000-100,000 cases of malignant tumor. We report a case of spontaneous regression of breast cancer with multiple pulmonary metastases. The patient was a 73-year-old woman who complained of a left mammary mass. A tumor, approximately 2.2 cm in diameter, was palpated, and breast cancer was suspected based on ultrasound examination. Histopathological findings of the core needle biopsy specimen indicated invasive ductal carcinoma. The patient underwent partial mastectomy with axillary lymph node dissection. It was a stage ⅡB (pT2N1 [sn] M0) tumor. CT performed after adjuvant therapy confirmed the presence of multiple pulmonary metastases 6 years after surgery. We started anti-cancer therapy with TS-1; however, it was discontinued because an adverse event occurred. Half a year later, tumor shrinkage was confirmed after a recurrence. Four years and 6 months after the treatment was discontinued, the tumor continued to regress spontaneously.}, } @article {pmid26805172, year = {2015}, author = {Sato, Y and Okishiro, M and Ohneda, Y and Motoyama, Y and Ishida, T and Morimoto, Y and Kusama, H and Matsushita, K and Hashimoto, T and Kimura, K and Naito, A and Murakami, K and Katsura, Y and Nitta, K and Ohmura, Y and Kagawa, Y and Takeno, A and Sakisaka, H and Taniguchi, H and Egawa, C and Takeda, Y and Kato, T and Tamura, S and Takatsuka, Y and Goto, T and Nagano, T and Nakatsuka, S}, title = {[A Case of Peritoneal Metastasis of Breast Cancer Diagnosed by Laparoscopic-Assisted Right Hemicolectomy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1785-1787}, pmid = {26805172}, issn = {0385-0684}, mesh = {Adenocarcinoma/*surgery ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/*pathology/*surgery ; Carcinoma, Ductal/drug therapy/*surgery ; Colectomy ; Female ; Humans ; Laparoscopy ; Peritoneal Neoplasms/*secondary/*surgery ; Recurrence ; Tamoxifen/therapeutic use ; Tegafur/therapeutic use ; Uracil/therapeutic use ; }, abstract = {The patient was an 86-year-old woman. She underwent right breast-conserving surgery and sentinel lymph node biopsy for breast cancer in August 2006. The pathological diagnosis was invasive ductal carcinoma, T1N0M0, Stage Ⅰ, ER (+), PgR (-), HER2 (-). She was treated with tamoxifen for 5 years as adjuvant therapy and showed no signs of recurrence. In November 2014, CA15-3 was elevated and an accumulation of FDG in the right paracolic sulcus was observed on PET-CT. Peritoneal metastasis of breast cancer was suspected, and an operation was performed for a definitive diagnosis. During the operation, the tumor was seen on the paracolic sulcus, and laparoscopic-assisted right hemicolectomy was performed. A poorly differentiated adenocarcinoma was diagnosed by pathological examination, and immunostaining results were as follows: CK7(+), CK20(-), mammaglobin (-), GCDFP-15 (-), ER (-), PgR (-), and HER2 (-). Because there was no original lesion other than the breast cancer, the tumor was diagnosed as a metastasis of breast cancer. The frequency of peritoneal metastasis of breast cancer is low. In this case, pathological diagnosis was necessary for a definitive diagnosis. A change of subtype was also confirmed, and the treatment strategy was decided appropriately. Surgical resection should be considered for peritoneal metastasis of breast cancer when the operation can be performed safely.}, } @article {pmid26805170, year = {2015}, author = {Takaoka, A and Nakagawa, T and Ogawa, N and Hayashi, M and Park, S and Iseki, H and Bei, Y}, title = {[HER2-Positive T1a Breast Cancer Metastatic to the Liver and Brain in a Patient Who Died Four Years and Three Months after Mastectomy--A Case Report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1779-1781}, pmid = {26805170}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary/*therapy ; Breast Neoplasms/chemistry/pathology/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/*therapy ; Mastectomy ; Middle Aged ; Receptor, ErbB-2/analysis ; }, abstract = {The prognosis of patients with T1a breast cancer is generally good, with a 5-year overall survival rate of 95%. However, HER2 overexpression is a risk factor for recurrence. A 46-year-old woman with left breast cancer underwent a total breast resection. The resected specimen showed invasive ductal carcinoma (T1a, NX, MX, g, ly0, v0, ER [-], PgR [-], HER2 [3+], Ki-67 20%). The patient did not receive adjuvant chemotherapy based on treatment guidelines. Nine months after the mastectomy, multiple liver metastases and severe acute hepatic insufficiency were found. The patient received chemotherapy with trastuzumab and paclitaxel, and a complete response was observed with disappearance of the liver metastases. One year and 11 months after the mastectomy, multiple brain metastases appeared. The patient received whole brain radiation therapy, Gamma Knife radiosurgery, and Cyber Knife radiosurgery. However, the brain metastasis could not be controlled, and the patient died 4 years and 3 months after mastectomy. HER2 positive T1a breast cancer should be observed carefully, and treatment with trastuzumab should be considered.}, } @article {pmid26805167, year = {2015}, author = {Sakurai, K and Fujisaki, S and Adachi, K and Suzuki, S and Masuo, Y and Nagashima, S and Hara, Y and Tomita, R and Gonda, K and Hirano, T and Enomoto, K and Amano, S}, title = {[Interval Breast Cancer with Neuroendocrine Differentiation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1770-1772}, pmid = {26805167}, issn = {0385-0684}, mesh = {Aged ; Breast Neoplasms/*pathology/surgery ; *Carcinoma, Ductal, Breast/surgery ; Carcinoma, Neuroendocrine ; Female ; Humans ; Mammography ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {We report a case of interval breast cancer that was an invasive ductal carcinoma of the breast with neuroendocrine differentiation. The patient was a 66-year-old woman who had a breast lump. She had received breast cancer screening every other year. The last screening was 1 year and 6 months prior to diagnosis. A core needle biopsy for breast tumor led to a diagnosis of invasive ductal carcinoma. Breast conserving surgery plus sentinel lymph node biopsy was performed. The pathological diagnosis from the resected surgical specimen was invasive ductal carcinoma with neuroendocrine differentiation, positive for ER and PgR, and negative for HER2/neu protein expression. The surgical margins were negative, and there was no metastasis in the sentinel lymph node. She was administered radiation therapy and adjuvant endocrine therapy. Two years after surgery, she is well without metastasis.}, } @article {pmid26805079, year = {2015}, author = {Kanada, Y and Matsuzaki, H and Kobayashi, H and Suzuki, K and Sawada, H and Senba, Y and Yoshioka, T and Note, H and Sato, Y and Miyazaki, A and Natsume, T and Tanaka, H and Maruyama, T}, title = {[A Case of Locally-Advanced Breast Cancer with Liver Metastasis, Treated with Mastectomy of the Primary Tumor after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {12}, pages = {1509-1511}, pmid = {26805079}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Epirubicin/administration & dosage ; Estrogen Replacement Therapy ; Female ; Humans ; Liver Neoplasms/*drug therapy/secondary ; Mastectomy ; Neoplasm Staging ; Tamoxifen/therapeutic use ; }, abstract = {The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage Ⅳbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy.}, } @article {pmid26804549, year = {2016}, author = {Fardmanesh, H and Shekari, M and Movafagh, A and Alizadeh Shargh, S and Poursadegh Zonouzi, AA and Shakerizadeh, S and Poursadegh Zonouzi, A and Hosseinzadeh, A}, title = {Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma.}, journal = {Gene}, volume = {581}, number = {2}, pages = {146-151}, doi = {10.1016/j.gene.2016.01.033}, pmid = {26804549}, issn = {1879-0038}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; RNA-Binding Proteins/*genetics ; *Up-Regulation ; }, abstract = {High-throughput experimental studies have indicated that the miRNAome is globally downregulated in various types of malignancy, and dysregulation of miRNAs processing component(s) is one possible mechanism for this phenomenon. Despite the progression in identifying cellular functions of Digeorge Syndrome Critical Region 8 (DGCR8) in miRNAs biogenesis, the role of altered expression of DGCR8 in the pathogenesis of invasive ductal breast carcinoma (IDC) has not yet been fully investigated. The objective of the present study was to evaluate DGCR8 mRNA expression in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissues using quantitative real-time PCR and to assess the value of clinicopathological parameters on its expression. Our findings revealed that DGCR8 mRNA expression is upregulated in more than two-thirds of the cancerous specimens (68.66%) when compared to adjacent non-neoplastic tissue. This difference is statistically significant (P<0.05). We found that DGCR8 mRNA levels were increased in the high-grade and metastatic compared with those of both low-grade and non-metastatic. We demonstrated that there is not significant correlation between DGCR8 mRNA expression levels and clinicopathological parameters. In conclusion, our study suggested that upregulation of DGCR8 may be involved in tumorigenesis and aggressiveness of IDC and may serve as future therapeutic target.}, } @article {pmid26801778, year = {2016}, author = {Woo, EJ and Baugh, AD and Ching, K}, title = {Synchronous presentation of invasive ductal carcinoma and mantle cell lymphoma: a diagnostic challenge in menopausal patients.}, journal = {Journal of surgical case reports}, volume = {2016}, number = {1}, pages = {}, pmid = {26801778}, issn = {2042-8812}, abstract = {Synchronous presentation of breast carcinoma and non-Hodgkin lymphoma (NHL) is a rare occurrence (Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol 2010; 146: :265-72; Dutta Roy S, Stafford JA, Scally J, Selvachandran SN. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma. World J Surg Oncol 2003; 1: :27; Suresh Attili VS, Dadhich HK, Rao CR, Bapsy PP, Batra U, Anupama G et al. A case of breast cancer coexisting with B-cell follicular lymphoma. Austral Asian J Cancer 2007; 6: :155-6). In particular, only two reported cases on synchronous presentation of invasive ductal carcinoma (IDC) and mantle cell lymphoma (MCL) exist in the English literature. Owing to the rarity, there is a lack of consensus about underlying mechanism as well as optimal treatment strategy, and diagnosing both malignancies together without a delay remains a complex clinical challenge. We report a case of synchronous presentation of IDC and MCL in a 67-year-old female patient whose MCL diagnosis was delayed due to a misinterpretation of her B symptoms as postmenopausal, with a review of the literature on concurrently occurring breast carcinoma and NHL.}, } @article {pmid26799412, year = {2016}, author = {Ladner, TR and Greenberg, JK and Guerrero, N and Olsen, MA and Shannon, CN and Yarbrough, CK and Piccirillo, JF and Anderson, RC and Feldstein, NA and Wellons, JC and Smyth, MD and Park, TS and Limbrick, DD}, title = {Chiari malformation Type I surgery in pediatric patients. Part 1: validation of an ICD-9-CM code search algorithm.}, journal = {Journal of neurosurgery. Pediatrics}, volume = {17}, number = {5}, pages = {519-524}, pmid = {26799412}, issn = {1933-0715}, support = {R24 HS019455/HS/AHRQ HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; *Algorithms ; Arnold-Chiari Malformation/*surgery ; Child ; Child, Preschool ; Confounding Factors, Epidemiologic ; Databases, Factual ; *Decompression, Surgical ; False Negative Reactions ; Female ; Humans ; Infant ; International Classification of Diseases ; *Laminectomy ; Male ; Midwestern United States ; New England ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Southeastern United States ; Treatment Outcome ; }, abstract = {OBJECTIVE Administrative billing data may facilitate large-scale assessments of treatment outcomes for pediatric Chiari malformation Type I (CM-I). Validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code algorithms for identifying CM-I surgery are critical prerequisites for such studies but are currently only available for adults. The objective of this study was to validate two ICD-9-CM code algorithms using hospital billing data to identify pediatric patients undergoing CM-I decompression surgery. METHODS The authors retrospectively analyzed the validity of two ICD-9-CM code algorithms for identifying pediatric CM-I decompression surgery performed at 3 academic medical centers between 2001 and 2013. Algorithm 1 included any discharge diagnosis code of 348.4 (CM-I), as well as a procedure code of 01.24 (cranial decompression) or 03.09 (spinal decompression or laminectomy). Algorithm 2 restricted this group to the subset of patients with a primary discharge diagnosis of 348.4. The positive predictive value (PPV) and sensitivity of each algorithm were calculated. RESULTS Among 625 first-time admissions identified by Algorithm 1, the overall PPV for CM-I decompression was 92%. Among the 581 admissions identified by Algorithm 2, the PPV was 97%. The PPV for Algorithm 1 was lower in one center (84%) compared with the other centers (93%-94%), whereas the PPV of Algorithm 2 remained high (96%-98%) across all subgroups. The sensitivity of Algorithms 1 (91%) and 2 (89%) was very good and remained so across subgroups (82%-97%). CONCLUSIONS An ICD-9-CM algorithm requiring a primary diagnosis of CM-I has excellent PPV and very good sensitivity for identifying CM-I decompression surgery in pediatric patients. These results establish a basis for utilizing administrative billing data to assess pediatric CM-I treatment outcomes.}, } @article {pmid26793897, year = {2016}, author = {Tsuzuki, T and Maeda, N and Murase, Y}, title = {[Recent advances in prostate pathology].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {74}, number = {1}, pages = {155-162}, pmid = {26793897}, issn = {0047-1852}, mesh = {Biopsy, Needle ; Humans ; Male ; Neoplasm Grading ; Practice Guidelines as Topic ; Prognosis ; Prostate/*pathology/surgery ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; }, abstract = {Gleason score was revised in 2005 by International Society of Urological Pathology (ISUP). This revision has great impacts on prostate cancer diagnosis and treatment. However, some issues were not reached to consensus. In addition, some modifications are needed to adapt recent advanced prostate cancer therapies, especially for patients with active surveillance and very high risk prostate cancer. The authors review recently updated Gleason grading system by ISUP, which will fit to recent prostate cancer treatment. There are few prognostic factors to predict cancer specific survival and overall survival. The authors show the concept and diagnostic criteria of IDC-P. The authors also discuss clinical usefulness and problems of IDC-P in practice.}, } @article {pmid26788154, year = {2015}, author = {Yagi, Y and Sasaki, S and Yoshikawa, A and Tsukioka, Y and Fukushima, W and Fujimura, T and Hirosawa, H and Izumi, R and Saito, K}, title = {Metastatic gastric carcinoma from breast cancer mimicking primary linitis plastica: A case report.}, journal = {Oncology letters}, volume = {10}, number = {6}, pages = {3483-3487}, pmid = {26788154}, issn = {1792-1074}, abstract = {Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.}, } @article {pmid26788152, year = {2015}, author = {Jin, G and Zhao, J and Yang, YI and Liu, K and Jiang, Y and Zhang, X and Zhang, Y and Huang, Y and Lu, J and Dong, Z}, title = {JAK/STAT3 signaling pathway mediates endothelial-like differentiation of immature dendritic cells.}, journal = {Oncology letters}, volume = {10}, number = {6}, pages = {3471-3477}, pmid = {26788152}, issn = {1792-1074}, abstract = {Endothelial-like differentiation (ELD) of dendritic cells (DCs) is a poorly understood phenomenon. The present study evaluated the effect on the ELD of DCs by using human esophageal squamous cell carcinoma (ESCC) cells with high or poor differentiation. The results demonstrated that KYSE450 (highly differentiated) and KYSE70 (poorly differentiated) cell supernatants induce the differentiation of immature DCs (iDCs), derived from healthy adult volunteers, away from the DC pathway and towards an endothelial cell (EC) fate. This effect was strongest in the cells treated with the KYSE70 supernatant. During the ELD of iDCs, sustained activation of JAK (janus tyrosine kinase)/STAT3 (signal transducer and activator of transcription 3) signaling was detected. Incubation of iDCs with the JAK inhibitor, AG490 blocked JAK/STAT3 phosphorylation and iDC differentiation. These results suggested that the JAK/STAT3 signaling pathway mediates ELD of iDCs. Furthermore, the poorly differentiated ESCC cells may have a greater effect on the ELD of iDCs than highly differentiated ESCC cells.}, } @article {pmid26786965, year = {2015}, author = {Levit-Binnun, N and Golland, Y}, title = {Adding network approaches to a neurobiological framework of resilience.}, journal = {The Behavioral and brain sciences}, volume = {38}, number = {}, pages = {e111}, doi = {10.1017/S0140525X14001617}, pmid = {26786965}, issn = {1469-1825}, mesh = {*Brain ; Humans ; *Neurobiology ; }, abstract = {In their paper, Kalisch et al. make an important attempt to create a unifying theoretical framework for the neuroscientific study of general resilience mechanisms. We suggest that such attempts can benefit tremendously by incorporating the recently emerging network approaches that enable the characterization of complex brain network architecture and dynamics, in both health and disease.}, } @article {pmid26784940, year = {2018}, author = {Kong, E and Chun, KA and Bae, YK and Cho, IH}, title = {Integrated PET/MR mammography for quantitative analysis and correlation to prognostic factors of invasive ductal carcinoma.}, journal = {The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...}, volume = {62}, number = {1}, pages = {118-126}, doi = {10.23736/S1824-4785.16.02825-X}, pmid = {26784940}, issn = {1827-1936}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; *Diffusion Magnetic Resonance Imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; *Mammography ; Middle Aged ; Multimodal Imaging ; Neoplasm Invasiveness ; *Positron-Emission Tomography ; Prognosis ; }, abstract = {BACKGROUND: We investigated the relationship between 18F-FDG PET parameters and apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DWI) in patients with invasive ductal carcinoma (IDC). In addition, the prognostic utility of PET/MR mammography parameters was compared with that of known histologic prognostic factors.

METHODS: Forty-six women aged 50.7±10.5 years underwent a preoperative PET/MR mammography assessment using an integrated PET/MR scanner. T1w, T2w, DWI (b value: 50, 400, and 800 s/mm2), dynamic contrast enhancement sequences, and 18F-FDG PET imaging were performed. IDCs were assessed using SUVmax values and intratumoral heterogeneities (IH) from the 18F-FDG PET images and mean (ADCmean) and minimum ADC (ADCmin) values were measured using the DWI images. Relationships between the PET parameters and ADC values were evaluated. Furthermore, SUVmax and ADC values were compared with histologic factors, tumor size, nodal status, lymphovascular invasion, Ki-67 expression and triple negative breast cancer (TNBC).

RESULTS: In total 46 IDCs (2.1-7.5 cm in size) were analyzed. SUVmax (P=0.012) and elevated IH (P=0.041) were negatively correlated with ADCmin, then TNBC (P=0.013) and high Ki-67 expression (P=0.002) were associated with higher SUVmax. IDC with lymphovascular invasion had low ADCmin values (P=0.045).

CONCLUSIONS: 18F-FDG PET metabolic parameters and ADCmin were negatively correlated. PET parameters and ADC values might reflect the expression of biological features of tumors and tumor invasiveness, respectively. Integrated PET/MR mammography seemed like to have potential of a one-stop method for evaluating and predicting the prognosis of IDC.}, } @article {pmid26782951, year = {2016}, author = {Jacobs, C and Clemons, M and Addison, C and Robertson, S and Arnaout, A}, title = {Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.}, journal = {The breast journal}, volume = {22}, number = {1}, pages = {45-53}, doi = {10.1111/tbj.12520}, pmid = {26782951}, issn = {1524-4741}, mesh = {Breast Neoplasms/*pathology/*therapy ; Carcinoma, Lobular/*pathology/*therapy ; Female ; Humans ; Magnetic Resonance Imaging ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Treatment Outcome ; }, abstract = {Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC.}, } @article {pmid26775637, year = {2016}, author = {Ghandour, RA and Giroud, M and Vegiopoulos, A and Herzig, S and Ailhaud, G and Amri, EZ and Pisani, DF}, title = {IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin.}, journal = {Biochimica et biophysica acta}, volume = {1861}, number = {4}, pages = {285-293}, doi = {10.1016/j.bbalip.2016.01.007}, pmid = {26775637}, issn = {0006-3002}, mesh = {Adipocytes, Brown/*drug effects/metabolism ; Adipocytes, White/*drug effects/metabolism ; Adipogenesis/*drug effects ; Anti-Obesity Agents/*pharmacology ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dose-Response Relationship, Drug ; Energy Metabolism/drug effects ; Enzyme Activation ; Epoprostenol/*analogs & derivatives/pharmacology ; Humans ; Infant ; Ion Channels/genetics/metabolism ; Male ; Mitochondrial Proteins/genetics/metabolism ; PPAR alpha/*agonists/genetics/metabolism ; PPAR gamma/*agonists/metabolism ; Phenotype ; RNA Interference ; Receptors, Epoprostenol ; Receptors, Prostaglandin/*agonists/metabolism ; Signal Transduction/drug effects ; Thermogenesis/drug effects ; Time Factors ; Transfection ; Uncoupling Protein 1 ; }, abstract = {Brite adipocytes recently discovered in humans are of considerable importance in energy expenditure by converting energy excess into heat. This property could be useful in the treatment of obesity, and nutritional aspects are relevant to this important issue. Using hMADS cells as a human cell model which undergoes a white to a brite adipocyte conversion, we had shown previously that arachidonic acid, the major metabolite of the essential nutrient Ω6-linoleic acid, plays a major role in this process. Its metabolites PGE2 and PGF2 alpha inhibit this process via a calcium-dependent pathway, whereas in contrast carbaprostacyclin (cPGI2), a stable analog of prostacyclin, activates white to brite adipocyte conversion. Herein, we show that cPGI2 generates via its cognate cell-surface receptor IP-R, a cyclic AMP-signaling pathway involving PKA activity which in turn induces the expression of UCP1. In addition, cPGI2 activates the pathway of nuclear receptors of the PPAR family, i.e. PPARα and PPARγ, which act separately from IP-R to up-regulate the expression of key genes involved in the function of brite adipocytes. Thus dual pathways are playing in concert for the occurrence of a browning process of human white adipocytes. These results make prostacyclin analogs as a new class of interesting molecules to treat obesity and associated diseases.}, } @article {pmid26775353, year = {2015}, author = {Qin, XJ and Gao, ZG and Huan, JL and Pan, XF and Zhu, L}, title = {Protein kinase D1 inhibits breast cancer cell invasion via regulating matrix metalloproteinase expression.}, journal = {European journal of gynaecological oncology}, volume = {36}, number = {6}, pages = {690-693}, pmid = {26775353}, issn = {0392-2936}, mesh = {Breast Neoplasms/enzymology/*pathology ; Cell Line, Tumor ; Female ; Humans ; Matrix Metalloproteinase 2/analysis ; Matrix Metalloproteinase 9/analysis ; Neoplasm Invasiveness ; Protein Kinase C/genetics/*physiology ; }, abstract = {PURPOSE: This study aimed to explore the role of protein kinase D1 (PKD1) in breast cancer invasion.

MATERIALS AND METHODS: The relative expression of PKD1mRNA and protein in human invasive breast cancer tissue samples and normal samples, as well as breast cancer cell lines, were detected. Constitutively-active PKD1 and PKD1 specific shRNA were expressed in the MD-MB-231 and MCF-7 cells, respectively. The role of PKD1 in the invasive behavior of breast cancer cell line was evaluated by matrix metalloproteinase (MMP) expression.

RESULTS: The results showed that PKD1, as a serine/threonine kinase, is downregulated significantly in invasive ductal carcinoma and metastatic invasive ductal carcinoma tissue than the normal tissue and the low expression of PKD1 is also found in breast cancer cell line MD-MB-231. The MMP2 and MMP9 expression in PKD1 constitutively-active MD-MB-231 cells and MCF-7 knockdown cells were decreased and increased respectively.

CONCLUSION: The authors confirmed that PKD1 was downregulated in invasive breast cancer. PKD1 can negatively regulate the MMP expression and may serve as a potential therapeutic target.}, } @article {pmid26774497, year = {2016}, author = {Jhaveri, K and Teplinsky, E and Silvera, D and Valeta-Magara, A and Arju, R and Giashuddin, S and Sarfraz, Y and Alexander, M and Darvishian, F and Levine, PH and Hashmi, S and Zolfaghari, L and Hoffman, HJ and Singh, B and Goldberg, JD and Hochman, T and Formenti, S and Esteva, FJ and Moran, MS and Schneider, RJ}, title = {Hyperactivated mTOR and JAK2/STAT3 Pathways: Molecular Drivers and Potential Therapeutic Targets of Inflammatory and Invasive Ductal Breast Cancers After Neoadjuvant Chemotherapy.}, journal = {Clinical breast cancer}, volume = {16}, number = {2}, pages = {113-22.e1}, pmid = {26774497}, issn = {1938-0666}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; R01 CA178509/CA/NCI NIH HHS/United States ; NIH/NCI 5 P30 CA16087/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Inflammatory Breast Neoplasms/drug therapy/metabolism/*pathology ; Janus Kinase 2/*metabolism ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/drug therapy/metabolism/pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; STAT3 Transcription Factor/*metabolism ; Signal Transduction/drug effects ; Survival Rate ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs).

PATIENTS AND METHODS: Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed.

RESULTS: Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2.

CONCLUSION: IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC.}, } @article {pmid26774154, year = {2016}, author = {Sobic Saranovic, D and Stojiljkovic, M and Susnjar, S and Odalovic, S and Artiko, V and Pavlovic, S and Grozdic-Milojevic, I and Obradovic, V}, title = {Metabolic activity of breast cancer metastatic lesions on positron emission tomography/computed tomography: comparison with histological and biological characteristics of primary tumor.}, journal = {Neoplasma}, volume = {63}, number = {2}, pages = {313-321}, doi = {10.4149/219_150813N440}, pmid = {26774154}, issn = {0028-2685}, mesh = {Bone Neoplasms/metabolism/secondary ; Breast Neoplasms/*diagnostic imaging/*pathology ; Energy Metabolism/*physiology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Glucose/*metabolism ; Humans ; Ki-67 Antigen/metabolism ; Liver Neoplasms/metabolism/secondary ; Lymph Nodes/metabolism ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Multimodal Imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Higher intensity of FDG uptake on PET/CT in primary tumor is seen in patients with IDC compared to ILC, also in high grade tumours, tumours with negative ER and higher Ki67 values, while data are inconsistent in case of relation between primary tumor's PgR and HER2 expression with its metabolic activity levels. On account of the lack of studies that include research of breast cancer metastatic lesion metabolism level and its relation to tumor histology and biology, our goal was to investigate the association of metastatic lesions' glucose metabolism level on PET/CT with different histological and biological characteristics of primary tumor. In a total number of N=100 patients, highest SUVmax values for each patient were used in testing difference between metastatic metabolic activity in patients with different tumor histology, grade, ER, PgR and HER2 status, subtype, as well in testing relation of Ki67 index to metastasis' metabolism level. In testing difference between histological types of breast cancer, SUVmax values were also compared separately for each specific anatomical site (regional and distant lymph nodes, bones and liver). No difference was found regarding metastatic SUVmax values in patients with primary IDC (n=55, median SUVmax 9.70) and ILC (n=34, median SUVmax 7.20) independently of anatomic site, and for each of analysed sites separately. No difference was found as well between SUVmax detected in metastasis in patients with different grade (grade II: n=58, median SUVmax 7.70; grade III: n=12, median SUVmax 10.20), ER (59 positive, median SUVmax 8.50; 22 negative, median SUVmax 8.05), PgR (55 positive, median SUVmax 8.50; 23 negative, median SUVmax 7.80), and HER2 (14 positive, median SUVmax 6.84; 51 negative, median SUVmax 8.63) expression in primary tumor, and between patients with different tumor subtype. Ki67 was also not associated with tumor metastatic SUVmax values (n=11, rs = -0.21, p=0.53). We conclude that there is no association of primary breast cancer histological type, grade, ER, PgR, HER2 and Ki67 expression with metabolic activity in metastasis detected on PET/CT.}, } @article {pmid26770622, year = {2015}, author = {Song, Q and Jin, Y and Huang, T and Zhang, JH}, title = {Diagnosis and treatment of Paget's disease of the breast: an analysis of 72 cases.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {10}, pages = {19616-19620}, pmid = {26770622}, issn = {1940-5901}, abstract = {OBJECTIVE: Clinical features, prognostic factors and principle of surgical treatment for Paget's disease of the breast were analyzed, so as to optimize the treatment of Pagent's disease of the breast.

METHOD: Seventy-two cases of Paget's disease of the breast treated at Affiliated Union Hospital and Hospital of Integrated Traditional Chinese and Western Medicine, Huazhong University of Science and Technology, from January 1991 to January 2010 were recruited. Their clinical data were analyzed retrospectively.

RESULTS: Among 72 cases, 52 cases had nipple-areolar complex lesions, 43 had palpable masses and 18 had palpable, enlarged axillary lymph nodes; 45 cases received radical mastectomy or modified radical mastectomy. Intraoperative pathological examination was performed for 9 cases who were not discovered to have breast lumps or enlarged axillary lymph nodes preoperatively; and 4 of them were diagnosed as lower axillary lymph node metastasis or invasive ductal carcinoma, and modified radical mastectomy was adopted for these cases. Fifty-two cases received postoperative pathological examination to reveal that the average number of metastatic lymph nodes was 3.1. Among the cases presenting with lymph node metastases, those negative for ER/PR accounted for 78%; Her-2-positive cases accounted for 56%. Thirty-seven cases were followed up for an average of 29 months postoperatively, and 5 of them were found with local recurrence and 7 with distant metastases.

CONCLUSION: Most cases of Paget's disease of the breast were associated with invasive ductal carcinoma and lymph node metastases. These cases had low ER/PR positive rate, high Her-2 positive rate and poor prognosis.}, } @article {pmid26770249, year = {2015}, author = {Lee, DH and Park, AY and Seo, BK and Kim, YS and Lee, KY and Cha, SH}, title = {Primary Neuroendocrine Carcinoma of the Breast with Clinical Features of Inflammatory Breast Carcinoma: A Case Report and Literature Review.}, journal = {Journal of breast cancer}, volume = {18}, number = {4}, pages = {404-408}, pmid = {26770249}, issn = {1738-6756}, abstract = {Primary neuroendocrine carcinoma of the breast (NECB) is a very rare type of invasive breast carcinoma. Most NECBs appear on breast imaging as solid masses of varied shapes and margins, and have worse clinical outcomes than does invasive ductal carcinoma, not otherwise specified. However, there have been no reports to date regarding NECB with features of inflammatory breast carcinoma. Here, we describe the clinical, radiol-ogic, and pathologic findings of the first reported case of primary NECB presenting as inflammatory breast carcinoma. The patient complained of diffuse right breast enlargement and erythema. Mammography identified severe breast edema and axillary lymphadenopathy. Ultrasound detected an irregular, angular, hypoechoic mass with dermal lymphatic dilatation. On magnetic resonance imaging, the mass had rim enhancement and the entire right breast showed heterogeneous enhancement with malignant kinetic features. Pathology identified the mass as a primary NECB with positive for synaptophysin, CD56, estrogen and progesterone receptors.}, } @article {pmid26769139, year = {2016}, author = {Thompson, E and Taube, JM and Elwood, H and Sharma, R and Meeker, A and Warzecha, HN and Argani, P and Cimino-Mathews, A and Emens, LA}, title = {The immune microenvironment of breast ductal carcinoma in situ.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {29}, number = {3}, pages = {249-258}, pmid = {26769139}, issn = {1530-0285}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*immunology/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Tissue Array Analysis ; Tumor Microenvironment/*immunology ; Young Adult ; }, abstract = {The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.}, } @article {pmid26768029, year = {2016}, author = {Canas-Marques, R and Schnitt, SJ}, title = {E-cadherin immunohistochemistry in breast pathology: uses and pitfalls.}, journal = {Histopathology}, volume = {68}, number = {1}, pages = {57-69}, doi = {10.1111/his.12869}, pmid = {26768029}, issn = {1365-2559}, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/pathology ; Carcinoma, Lobular/*diagnosis/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; }, abstract = {E-cadherin immunohistochemistry is used commonly in surgical pathology practice to help distinguish lobular carcinoma in situ from ductal carcinoma in situ and invasive lobular carcinoma from invasive ductal carcinoma in histologically problematic or indeterminate cases. However, the interpretation of E-cadherin immunostains is not always straightforward. Failure to recognize the pitfalls and limitations of E-cadherin immunostains can lead to an erroneous diagnosis which may result in inappropriate patient management, particularly for patients with in-situ lesions. In this paper we review the uses and, particularly, the pitfalls in the interpretation of E-cadherin immunostains in distinguishing lobular from ductal lesions of the breast.}, } @article {pmid26762957, year = {2016}, author = {Kalogera, E and Pistos, C and Provatopoulou, X and Christophi, CA and Zografos, GC and Stefanidou, M and Spiliopoulou, C and Athanaselis, S and Gounaris, A}, title = {Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer.}, journal = {Journal of chromatographic science}, volume = {54}, number = {4}, pages = {583-592}, pmid = {26762957}, issn = {1945-239X}, mesh = {Androgens/*blood ; Breast Neoplasms/*blood ; Chromatography, High Pressure Liquid/*methods ; Female ; Glucuronides/*blood ; Humans ; Limit of Detection ; Mass Spectrometry/*methods ; Reproducibility of Results ; }, abstract = {The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05).}, } @article {pmid26756416, year = {2016}, author = {Sutton, EJ and Dashevsky, BZ and Oh, JH and Veeraraghavan, H and Apte, AP and Thakur, SB and Morris, EA and Deasy, JO}, title = {Breast cancer molecular subtype classifier that incorporates MRI features.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {44}, number = {1}, pages = {122-129}, pmid = {26756416}, issn = {1522-2586}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Algorithms ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/classification/*diagnostic imaging/*metabolism ; Diagnosis, Differential ; Female ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Observer Variation ; Reproducibility of Results ; Sensitivity and Specificity ; Triple Negative Breast Neoplasms/diagnostic imaging ; }, abstract = {PURPOSE: To use features extracted from magnetic resonance (MR) images and a machine-learning method to assist in differentiating breast cancer molecular subtypes.

MATERIALS AND METHODS: This retrospective Health Insurance Portability and Accountability Act (HIPAA)-compliant study received Institutional Review Board (IRB) approval. We identified 178 breast cancer patients between 2006-2011 with: 1) ERPR + (n = 95, 53.4%), ERPR-/HER2 + (n = 35, 19.6%), or triple negative (TN, n = 48, 27.0%) invasive ductal carcinoma (IDC), and 2) preoperative breast MRI at 1.5T or 3.0T. Shape, texture, and histogram-based features were extracted from each tumor contoured on pre- and three postcontrast MR images using in-house software. Clinical and pathologic features were also collected. Machine-learning-based (support vector machines) models were used to identify significant imaging features and to build models that predict IDC subtype. Leave-one-out cross-validation (LOOCV) was used to avoid model overfitting. Statistical significance was determined using the Kruskal-Wallis test.

RESULTS: Each support vector machine fit in the LOOCV process generated a model with varying features. Eleven out of the top 20 ranked features were significantly different between IDC subtypes with P < 0.05. When the top nine pathologic and imaging features were incorporated, the predictive model distinguished IDC subtypes with an overall accuracy on LOOCV of 83.4%. The combined pathologic and imaging model's accuracy for each subtype was 89.2% (ERPR+), 63.6% (ERPR-/HER2+), and 82.5% (TN). When only the top nine imaging features were incorporated, the predictive model distinguished IDC subtypes with an overall accuracy on LOOCV of 71.2%. The combined pathologic and imaging model's accuracy for each subtype was 69.9% (ERPR+), 62.9% (ERPR-/HER2+), and 81.0% (TN).

CONCLUSION: We developed a machine-learning-based predictive model using features extracted from MRI that can distinguish IDC subtypes with significant predictive power. J. Magn. Reson. Imaging 2016;44:122-129.}, } @article {pmid26756228, year = {2016}, author = {Eyal, K and Te'eni-Harari, T}, title = {High on Attractiveness, Low on Nutrition: An Over-Time Comparison of Advertising Food Products on Israeli Television.}, journal = {Health communication}, volume = {31}, number = {8}, pages = {988-997}, doi = {10.1080/10410236.2015.1026431}, pmid = {26756228}, issn = {1532-7027}, mesh = {Adolescent ; Adult ; *Advertising ; Beverages ; Body Image/*psychology ; Child ; Fast Foods ; *Food ; Humans ; Israel ; Middle Aged ; Nutritional Status/*physiology ; Obesity/prevention & control ; Television/statistics & numerical data ; }, abstract = {This content analysis examines Israeli television food advertising. It compares 2008-2009 and 2012-2013, two periods immediately before and several years after regulatory, educational, and public-advocacy efforts have been advanced to raise awareness of and tackle the television-obesity link. Advertisements were drawn from a composite week sample aired on Israeli broadcast channels from 4:00 p.m. until midnight in each of the two periods. Nearly a quarter of ads were for food products, even after a significant drop over the years. The most common food categories included candies and sweetened drinks, whereas fruit and vegetables were among the least common products advertised. The most prevalent central message in food advertisements was that the product makes for an economically sensible purchase, with a much lower focus on the health qualities of the food products. Food advertisements were characterized by a very short duration and an increased reliance on emotional, rather than cognitive, appeal, especially in ads for low-nutrient foods. A significant increase was observed in 2012-2013 in the reliance on thin models in food advertisements, and these were most often associated with high levels of physical attractiveness, promoting the thin ideal. Findings are discussed in light of theory, previous research conducted worldwide, and audience effects. Implications are addressed for health and media industry regulation efforts.}, } @article {pmid26752563, year = {2016}, author = {Raghav, K and French, JT and Ueno, NT and Lei, X and Krishnamurthy, S and Reuben, JM and Valero, V and Ibrahim, NK}, title = {Inflammatory Breast Cancer: A Distinct Clinicopathological Entity Transcending Histological Distinction.}, journal = {PloS one}, volume = {11}, number = {1}, pages = {e0145534}, pmid = {26752563}, issn = {1932-6203}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Carcinoma, Ductal, Breast/diagnosis/mortality/*pathology/surgery ; Carcinoma, Lobular/diagnosis/mortality/*pathology/surgery ; Female ; Histocytochemistry ; Humans ; Inflammatory Breast Neoplasms/diagnosis/mortality/*pathology/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis/mortality/*pathology/surgery ; Phenotype ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Although well recognized in breast oncology literature, histologic subtypes have not been previously described in inflammatory breast cancer (IBC). The purpose of this study was to describe lobular subtype in IBC and assess the impact of histology on patient outcomes.

METHODS: We performed a retrospective analysis of 659 IBC patients at MD Anderson Cancer Center between January 1984 and December 2009. Patients with Invasive Lobular, Mixed Invasive Ductal and Lobular, or Invasive Ducal Carcinomas (ILC, MIC, IDC, respectively) comprise the subject of this report. Patient characteristics and survival estimates were compared by using chi-square test and Kaplan-Meier method with log-rank statistic. Cox proportional hazards models were fit to determine association of histology with outcomes after adjustment for other characteristics.

RESULTS: A total of 30, 37, and 592 patients were seen to have invasive lobular, mixed, or ductal histology, respectively. Grade 3 tumors were more common in the ductal group (78%) than in the lobular (60%) or mixed (61%) group (P = 0.01). The 3-year overall survival rates were 68%, 64%, and 62% in the lobular, mixed, and ductal groups, respectively (P = 0.68). After adjustment, histology did not have a significant effect on death in the lobular group (HR = 0.70, 95% confidence interval [CI]: 0.26-1.94; P = 0.50) or mixed group (HR = 0.53, 95% CI: 0.25-1.13; P = 0.10) compared with the ductal group.

CONCLUSION: In this cohort of IBC patients, lobular histology was seen in 4.5% cases. Histology does not appear to have a significant effect on survival outcomes in IBC patients, unlike in patients with non-inflammatory breast cancer (n-IBC), indicating the distinct biological behavior of the IBC phenotype.}, } @article {pmid26745902, year = {2016}, author = {Dalmış, MU and Gubern-Mérida, A and Vreemann, S and Karssemeijer, N and Mann, R and Platel, B}, title = {A computer-aided diagnosis system for breast DCE-MRI at high spatiotemporal resolution.}, journal = {Medical physics}, volume = {43}, number = {1}, pages = {84}, doi = {10.1118/1.4937787}, pmid = {26745902}, issn = {2473-4209}, mesh = {Algorithms ; Aorta ; Breast Neoplasms/*diagnosis ; *Contrast Media ; Diagnosis, Computer-Assisted/*methods ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; *Signal-To-Noise Ratio ; }, abstract = {PURPOSE: With novel MRI sequences, high spatiotemporal resolution has become available in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast. Since benign structures in the breast can show enhancement similar to malignancies in DCE-MRI, characterization of detected lesions is an important problem. The purpose of this study is to develop a computer-aided diagnosis (CADx) system for characterization of breast lesions imaged with high spatiotemporal resolution DCE-MRI.

METHODS: The developed CADx system is composed of four main parts: semiautomated lesion segmentation, automated computation of morphological and dynamic features, aorta detection, and classification between benign and malignant categories. Lesion segmentation is performed by using a "multiseed smart opening" algorithm. Five morphological features were computed based on the segmentation of the lesion. For each voxel, contrast enhancement curve was fitted to an exponential model and dynamic features were computed based on this fitted curve. Average and standard deviations of the dynamic features were computed over the entire segmented area, in addition to the average value in an automatically selected smaller "most suspicious region." To compute the dynamic features for an enhancement curve, information of aortic enhancement is also needed. To keep the system fully automated, the authors developed a component which automatically detects the aorta and computes the aortic enhancement time. The authors used random forests algorithm to classify benign lesions from malignant. The authors evaluated this system in a dataset of breast MRI scans of 325 patients with 223 malignant and 172 benign lesions and compared its performance to an existing approach. The authors also evaluated the classification performances for ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) lesions separately. The classification performances were measured by receiver operating characteristic (ROC) analysis in a leave-one-out cross validation scheme.

RESULTS: The area under the ROC curve (AUC) obtained by the proposed CADx system was 0.8543, which was significantly higher (p = 0.007) than the performance obtained by the previous CADx system (0.8172) on the same dataset. The AUC values for DCIS, IDC, and ILC lesions were 0.7924, 0.8688, and 0.8650, respectively.

CONCLUSIONS: The authors developed a CADx system for high spatiotemporal resolution DCE-MRI of the breast. This system outperforms a previously proposed system in classifying benign and malignant lesions, while it requires less user interactions.}, } @article {pmid26745092, year = {2015}, author = {Bandala, C and De la Garza-Montano, P and Cortes-Algara, A and Cruz-Lopez, J and Dominguez-Rubio, R and Gonzalez-Lopez, JN and Cardenas-Rodriguez, N and Alfaro-Rodriguez, A and Salcedo, M and Floriano-Sanchez, E and Lara-Padilla, E}, title = {Association of Histopathological Markers with Clinico- Pathological Factors in Mexican Women with Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {18}, pages = {8397-8403}, doi = {10.7314/apjcp.2015.16.18.8397}, pmid = {26745092}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/*metabolism ; Mexico/epidemiology ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors.

MATERIALS AND METHODS: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied.

RESULTS: On average, patients were 58±10.4 years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p <0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subtype was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02).

CONCLUSIONS: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.}, } @article {pmid26745061, year = {2015}, author = {Bulut, G and Kosem, M and Bulut, MD and Erten, R and Bayram, I}, title = {Is Immunohistochemical Sex Hormone Binding Globulin Expression Important in the Differential Diagnosis of Adenocarcinomas?.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {18}, pages = {8203-8210}, doi = {10.7314/apjcp.2015.16.18.8203}, pmid = {26745061}, issn = {2476-762X}, mesh = {Adenocarcinoma/*classification/*diagnosis/metabolism ; Biomarkers, Tumor/*metabolism ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Neoplasm Staging ; Neoplasms/*diagnosis/metabolism ; Prognosis ; Sex Hormone-Binding Globulin/*metabolism ; }, abstract = {Adenocarcinomas (AC) are the most frequently encountered carcinomas. It may be quite challenging to detect the primary origin when those carcinomas metastasize and the first finding is a metastatic tumor. This study evaluated the role of sex hormone binding globulin (SHBG) positivity in tumor cells in the subclassification and detection of the original organ of adenocarcinomas. Between 1994 and 2008, 64 sections of normal tissue belonging to ten organs, and 116 cases diagnosed as adenoid cystic carcinoma and mucoepidermoid carcinoma of the salivary gland, lung adenocarcinoma, invasive ductal carcinoma of the breast, adenocarcinoma of stomach, colon, gallbladder, pancreas and prostate, endometrial adenocarcinoma and serous adenocarcinoma and mucinous adenocarcinoma of the ovary, were sent to the laboratory at the Department of Pathology at the Yuzuncu Yil University School of Medicine, where they were stained immunohistochemically, using antibodies against SHBG. The SHBG immunoreactivity in both the tumor cells and normal cells, together with the type, diffuseness and intensity of the staining were then evaluated. In the differential diagnosis of the adenocarcinomas of the organs, including the glandular structures, impressively valuable results are encountered in the tumor cells, whether the SHBG immunopositivity is evaluated alone or together with other IHC markers. Further extensive research with a larger number of cases, including instances of cholangiocarcinoma and cervix uteri AC [which we could not include in the study for technical reasons] should be performed, in order to appropriately evaluate the role of SHBG in the differential diagnosis of AC.}, } @article {pmid26744317, year = {2016}, author = {Riku, M and Inaguma, S and Ito, H and Tsunoda, T and Ikeda, H and Kasai, K}, title = {Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis.}, journal = {Oncotarget}, volume = {7}, number = {5}, pages = {5690-5701}, pmid = {26744317}, issn = {1949-2553}, mesh = {Apoptosis ; Blotting, Western ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carboxypeptidases/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Case-Control Studies ; Cell Proliferation ; Cell Transformation, Neoplastic/*genetics/pathology ; Cells, Cultured ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR4/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcriptional Activation ; Zinc Finger Protein GLI1/genetics/*metabolism ; }, abstract = {Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1.}, } @article {pmid26740749, year = {2015}, author = {Makki, J}, title = {Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance.}, journal = {Clinical medicine insights. Pathology}, volume = {8}, number = {}, pages = {23-31}, pmid = {26740749}, issn = {1179-5557}, abstract = {Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of >1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.}, } @article {pmid26739446, year = {2016}, author = {Picillo, M and Santangelo, G and Moccia, M and Erro, R and Amboni, M and Prestipino, E and Longo, K and Vitale, C and Spina, E and Orefice, G and Barone, P and Pellecchia, MT}, title = {Serum uric acid is associated with apathy in early, drug-naïve Parkinson's disease.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {123}, number = {4}, pages = {371-377}, pmid = {26739446}, issn = {1435-1463}, mesh = {Aged ; *Apathy ; Biomarkers/*blood ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*blood/diagnosis/*psychology ; Uric Acid/*blood ; }, abstract = {Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.}, } @article {pmid26737267, year = {2015}, author = {Sugitani, T and Arihiro, K and Kikkawa, T}, title = {Comparative study on dielectric constants and conductivities of invasive ductal carcinoma tissues.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2015}, number = {}, pages = {4387-4390}, doi = {10.1109/EMBC.2015.7319367}, pmid = {26737267}, issn = {2694-0604}, mesh = {*Breast Neoplasms ; Humans ; }, abstract = {Measurements of dielectric constants and conductivities of invasive ductal carcinoma (IDC) tissues such as scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma were made by use of microwave dielectric spectroscopy. Dielectric constants of inhomogeneous breast tumor tissues were analyzed by use of Bruggeman's effective medium approximation theory. It is found that the dielectric constants of scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma of IDC tissues have correlation to the volume fractions of the cancer cells in the stroma tissues.}, } @article {pmid26730350, year = {2015}, author = {Sarraj, WM and Tang, R and Najjar, AL and Griffin, M and Bui, AH and Zambeli-Ljepovic, A and Senter-Zapata, M and Lewin-Berlin, M and Fernandez, L and Buckley, J and Ly, A and Brachtel, E and Aftreth, O and Gilbertson, J and Yagi, Y and Gadd, M and Hughes, KS and Smith, BL and Michaelson, JS}, title = {Prediction of primary breast cancer size and T-stage using micro-computed tomography in lumpectomy specimens.}, journal = {Journal of pathology informatics}, volume = {6}, number = {}, pages = {60}, pmid = {26730350}, issn = {2229-5089}, abstract = {BACKGROUND: Histopathology is the only accepted method to measure and stage the breast tumor size. However, there is a need to find another method to measure and stage the tumor size when the pathological assessment is not available. Micro-computed tomography. (micro-CT) has the ability to measure tumor in three dimensions in an intact lumpectomy specimen. In this study, we aimed to determine the accuracy of micro-CT to measure and stage the primary tumor size in breast lumpectomy specimens, as compared to the histopathology.

MATERIALS AND METHODS: Seventy-two women who underwent lumpectomy surgery at the Massachusetts General Hospital Department of Surgery from June 2011 to September 2011, and from August 2013 to December 2013 participated in this study. The lumpectomy specimens were scanned using micro-CT followed by routine pathological processing. The maximum dimension of the invasive breast tumor was obtained from the micro-CT image and was compared to the corresponding pathology report for each subject.

RESULTS: The invasive tumor size measurement by micro-CT was underestimated in 24 cases. (33%), overestimated in 37 cases. (51%), and matched it exactly in 11 cases. (15%) compared to the histopathology measurement for all the cases. However, micro-CT T-stage classification differed from histopathology in only 11. (15.2%) with 6 cases. (8.3%) classified as a higher stage by micro-CT, and 5 cases. (6.9%) classified as lower compared to histopathology. In addition, micro-CT demonstrated a statically significant strong agreement (κ =0.6, P < 0.05) with pathological tumor size and staging for invasive ductal carcinoma. (IDC) group. In contrast, there was no agreement. (κ = -2, P = 0.67) between micro-CT and pathology in estimating and staging tumor size for invasive lobular carcinoma. (ILC) group. This could be explained by a small sample size. (7) for ILC group.

CONCLUSIONS: Micro-CT is a promising modality for measuring and staging the IDC.}, } @article {pmid26730066, year = {2015}, author = {Koley, S and Chakrabarti, S and Pathak, S and Manna, AK and Basu, S}, title = {Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.}, journal = {The Indian journal of surgery}, volume = {77}, number = {Suppl 2}, pages = {570-575}, pmid = {26730066}, issn = {0972-2068}, abstract = {Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.}, } @article {pmid26729235, year = {2016}, author = {Michaut, M and Chin, SF and Majewski, I and Severson, TM and Bismeijer, T and de Koning, L and Peeters, JK and Schouten, PC and Rueda, OM and Bosma, AJ and Tarrant, F and Fan, Y and He, B and Xue, Z and Mittempergher, L and Kluin, RJ and Heijmans, J and Snel, M and Pereira, B and Schlicker, A and Provenzano, E and Ali, HR and Gaber, A and O'Hurley, G and Lehn, S and Muris, JJ and Wesseling, J and Kay, E and Sammut, SJ and Bardwell, HA and Barbet, AS and Bard, F and Lecerf, C and O'Connor, DP and Vis, DJ and Benes, CH and McDermott, U and Garnett, MJ and Simon, IM and Jirström, K and Dubois, T and Linn, SC and Gallagher, WM and Wessels, LF and Caldas, C and Bernards, R}, title = {Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {18517}, pmid = {26729235}, issn = {2045-2322}, support = {102696/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics/*metabolism/mortality ; Carcinoma, Lobular/diagnosis/*genetics/*metabolism ; Cluster Analysis ; DNA-Binding Proteins/genetics/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Profiling ; *Genomics/methods ; Humans ; Immunohistochemistry ; Mutation Rate ; Polymorphism, Single Nucleotide ; Prognosis ; *Proteome ; Proteomics ; Reproducibility of Results ; Transcription Factors/genetics/metabolism ; *Transcriptome ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.}, } @article {pmid26722353, year = {2016}, author = {Berry, JS and Trappey, AF and Vreeland, TJ and Pattyn, AR and Clifton, GT and Berry, EA and Schneble, EJ and Kirkpatrick, AD and Saenger, JS and Peoples, GE}, title = {Analysis of Clinical and Pathologic Factors of Pure, Flat Epithelial Atypia on Core Needle Biopsy to Aid in the Decision of Excision or Observation.}, journal = {Journal of Cancer}, volume = {7}, number = {1}, pages = {1-6}, pmid = {26722353}, issn = {1837-9664}, abstract = {BACKGROUND: The optimal treatment of flat epithelial atypia (FEA) found on breast core needle biopsy (CNB) is controversial. We performed a retrospective review of our institutional experience with FEA to determine if excisional biopsy may be deferred.

METHODS: Surgical records from 2009 to 2012 were reviewed for FEA diagnosis. After exclusion for concomitant lesions, CNBs of pure FEA were classified using a previously agreed upon descriptor of "focal" versus "prominent". Data was analyzed with the Fisher's Exact and Student-t test as appropriate.

RESULTS: Of 71 CNBs evaluated, pure FEA was identified on 27 CNBs. Final excisional biopsy was benign in 24 of 27 cases (88%) with associated ductal carcinoma in-situ (DCIS) in 3 of 27 cases (11%). Eighteen of 27 (67%) CNBs were classified as focal while 9 (33%) were described as prominent. Zero of the 18 focal patients had a malignancy compared to 3 of the 9 in the prominent group (0% vs 33%, p=0.02). Of the 27 pure FEA CNBs, 6 patients had a personal history of breast carcinoma, five DCIS and one invasive ductal carcinoma. No malignancies were found in the 21 patients without a personal history of breast carcinoma versus three in the patients with a positive history (0/21 v 3/6, p=0.007).

CONCLUSIONS: Our data suggests those women who have adequate sampling and sectioning of CNBs, with focal, pure FEA on pathology, and are without a personal history of breast cancer may undergo a period of imaging surveillance. Conversely, patients with a history of breast cancer or pure, prominent FEA on CNB disease should proceed to excisional biopsy.}, } @article {pmid26721716, year = {2016}, author = {Wang, L and Lyu, S and Wang, S and Shen, H and Niu, F and Liu, X and Liu, J and Niu, Y}, title = {Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer.}, journal = {Experimental and molecular pathology}, volume = {100}, number = {1}, pages = {177-183}, doi = {10.1016/j.yexmp.2015.12.012}, pmid = {26721716}, issn = {1096-0945}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology/therapy ; Disease Progression ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Receptors, Estrogen/metabolism ; Treatment Outcome ; beta Catenin/metabolism ; }, abstract = {FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.}, } @article {pmid26715212, year = {2016}, author = {Nakagawa, S and Miki, Y and Miyashita, M and Hata, S and Takahashi, Y and Rai, Y and Sagara, Y and Ohi, Y and Hirakawa, H and Tamaki, K and Ishida, T and Watanabe, M and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.}, journal = {Breast cancer research and treatment}, volume = {155}, number = {1}, pages = {65-75}, doi = {10.1007/s10549-015-3668-9}, pmid = {26715212}, issn = {1573-7217}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Angiogenesis Inducing Agents/metabolism ; Antigens, CD34/metabolism ; Biomarkers ; Breast Neoplasms/genetics/*metabolism/*pathology/therapy ; Carcinoma, Lobular/genetics/*metabolism/*pathology/therapy ; Cell Cycle Proteins/metabolism ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor I/genetics/metabolism ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Nestin/metabolism ; Receptor, IGF Type 1/genetics/metabolism ; Tumor Burden ; *Tumor Microenvironment/genetics ; }, abstract = {Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.}, } @article {pmid26712408, year = {2015}, author = {Wang, L and Mi, C and Wang, W}, title = {[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].}, journal = {Zhonghua yi xue za zhi}, volume = {95}, number = {23}, pages = {1862-1865}, pmid = {26712408}, issn = {0376-2491}, mesh = {Animals ; *Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Mice ; Mice, Nude ; }, abstract = {OBJECTIVE: To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses.

METHODS: Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination.

RESULTS: ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node.

CONCLUSIONS: The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.}, } @article {pmid26712255, year = {2015}, author = {Moschetta, M and Telegrafo, M and Introna, T and Coi, L and Rella, L and Ranieri, V and Cirili, A and Stabile Ianora, AA and Angelelli, G}, title = {Role of specimen US for predicting resection margin status in breast conserving therapy.}, journal = {Il Giornale di chirurgia}, volume = {36}, number = {5}, pages = {201-204}, pmid = {26712255}, issn = {0391-9005}, mesh = {Adenocarcinoma, Mucinous/*diagnostic imaging/epidemiology/surgery ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/epidemiology/*surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/epidemiology/surgery ; Carcinoma, Lobular/*diagnostic imaging/epidemiology/surgery ; Female ; Humans ; Italy/epidemiology ; *Mastectomy, Segmental/methods ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Treatment Outcome ; Ultrasonography ; }, abstract = {AIM: To assess the diagnostic accuracy of specimen ultrasound (US) for predicting resection margin status in women undergoing breast conserving therapy for US-detected cancer, having the histological findings as the reference standard.

PATIENTS AND METHODS: A total of 132 consecutive patients (age range, 34-87 years; mean, 51 years) underwent breast-conserving surgery for US-detected invasive breast cancer. All surgical specimens underwent US examination. The presence of lesion within the specimen and its distance from the specimen margins were assessed considering a threshold distance between the lesion and specimen margins of 10 mm. US findings were then compared with the pathological ones and specimen US. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) for predicting histological margin status were evaluated, having the histological findings as the reference standard.

RESULTS: The histological examination detected invasive ductal carcinoma in 96/132 (73%) cases, invasive lobular carcinoma in 32/132 (24%), mucinous carcinoma in 4/132 (3%). The pathological margin analysis revealed 96/132 (73%) negative margins and 36 (27%) close/positive margins. US examination detected all 132 breast lesions within the surgical specimens. 110 (83%) negative margins and 22 (17%) positive margins were found on US. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 44%, 94%, 80%, 73% and 82%, respectively, were found for specimen US.

CONCLUSIONS: Specimen US represents a time and cost saving imaging tool for evaluating the presence of US detected-breast lesion within surgical specimen and for predicting the histological margin status.}, } @article {pmid26703116, year = {2016}, author = {Langlands, F and White, J and Kearins, O and Cheung, S and Burns, R and Horgan, K and Sharma, N and Dodwell, D}, title = {Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary.}, journal = {Clinical radiology}, volume = {71}, number = {2}, pages = {159-163}, doi = {10.1016/j.crad.2015.10.030}, pmid = {26703116}, issn = {1365-229X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/therapy ; Carcinoma, Lobular/*epidemiology/therapy ; Female ; Humans ; Incidence ; Middle Aged ; Registries/statistics & numerical data ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {AIM: To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC).

MATERIALS AND METHODS: Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998-2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases.

RESULTS: A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer.

CONCLUSION: There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning breast-conservation surgery, but not for assessing the contralateral breast.}, } @article {pmid26697511, year = {2015}, author = {Manickam, K and Reddy, MR and Seshadri, S and Raghavan, B}, title = {Development of a training phantom for compression breast elastography-comparison of various elastography systems and numerical simulations.}, journal = {Journal of medical imaging (Bellingham, Wash.)}, volume = {2}, number = {4}, pages = {047002}, pmid = {26697511}, issn = {2329-4302}, abstract = {The elastic properties of tissue are related to tissue composition and pathological changes. It has been observed that many pathological processes increase the elastic modulus of soft tissue compared to normal. Ultrasound compression elastography is a method of characterization of elastic properties that has been the focus of many research efforts in the last two decades. In medical radiology, compression elastography is provided as an additional tool with ultrasound B-mode in the existing scanners, and the combined features of elastography and echography act as a promising diagnostic method in breast cancer detection. However, the full capability of the ultrasound elastography technique together with B-mode has not been utilized by novice radiologists due to the nonavailability of suitable, appropriately designed tissue-mimicking phantoms. Since different commercially available ultrasound elastographic scanners follow their own unique protocols, training novice radiologists is becoming cumbersome. The main focus of this work is to develop a tissue-like agar-based phantom, which mimics breast tissue with common abnormal lesions like fibroadenoma and invasive ductal carcinoma in a clinically perceived way and compares the sonographic and elastographic appearances using different commercially available systems. In addition, the developed phantoms are simulated using the finite-element method, and ideal strain images are generated. Strain images from experiment and simulation are compared based on image contrast parameters, namely contrast transfer efficiency (CTE) and observed strain, and they are in good agreement. The strain image contrast of malignant inclusions is significantly improved compared to benign inclusions, and the trend of CTE is similar for all elastographic scanners under investigation.}, } @article {pmid26697228, year = {2015}, author = {Vasudevan, D and Jayalakshmy, PS and Kumar, S and Mathew, S}, title = {Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy.}, journal = {International journal of breast cancer}, volume = {2015}, number = {}, pages = {536145}, pmid = {26697228}, issn = {2090-3170}, abstract = {Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT) in the setting of locally advanced breast cancer (LABC) can render inoperable tumor (T4, N2/N3) resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma (n = 48) were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier's system which graded the responses into pathological complete response (pCR), pathological partial response (pPR), and pathological no response (pNR). Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2-5 cms) and Bloom Richardson's grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response.}, } @article {pmid26690243, year = {2015}, author = {Ito, M and Shien, T and Kaji, M and Mizoo, T and Iwamoto, T and Nogami, T and Motoki, T and Taira, N and Doihara, H and Miyoshi, S}, title = {Correlation between 18F-fluorodeoxyglucose Positron Emission Tomography/computed Tomography and Clinicopathological Features in Invasive Ductal Carcinoma of the Breast.}, journal = {Acta medica Okayama}, volume = {69}, number = {6}, pages = {333-338}, doi = {10.18926/AMO/53907}, pmid = {26690243}, issn = {0386-300X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Ki-67 Antigen/analysis ; Middle Aged ; Positron-Emission Tomography/*methods ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; }, abstract = {We evaluated the usefulness of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examinations to predict the pathological features in primary breast cancer. In particular, we evaluated the correlation between the maximum standardized uptake values (SUVmax) obtained by 18F-FDG PET/CT and the Ki67 expression in estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). Primary IDC patients operated between March 2009 and July 2013 at Okayama University Hospital were enrolled. We evaluated the correlations between the SUVmax and age, postoperative pT, histological grade, lymph vascular invasion, status of hormone receptor, human epidermal growth factor receptor 2 (HER2), Ki67 expression and node status. The Ki67 expression was classified as high (＞ 14%) versus low (< 14%). We enrolled 138 patients with IDC. Their median SUVmax was 3.85 (range:0-52.57). In a univariate analysis, the SUVmax was significantly related to age, pT, histological grade, lymphovascular invasion, hormone receptor status, HER2 status, node status and Ki67. In the 113 patients with ER-positive IDC, there was a significant correlation between Ki67 and SUVmax (p ＝ 0.0030). The preoperative 18F-FDG PET/CT results of IDC patients had significant relationships with pathological status parameters. The determination of the preoperative SUVmax might help classify Luminal A and Luminal B patients among luminal-type breast cancer patients.}, } @article {pmid26689295, year = {2016}, author = {Vélez-Vélez, E and Bosch, RJ}, title = {Illness perception, coping and adherence to treatment among patients with chronic kidney disease.}, journal = {Journal of advanced nursing}, volume = {72}, number = {4}, pages = {849-863}, doi = {10.1111/jan.12873}, pmid = {26689295}, issn = {1365-2648}, mesh = {*Adaptation, Psychological ; Adult ; Aged ; Attitude to Health ; Cross-Sectional Studies ; Female ; Humans ; Illness Behavior ; Male ; Middle Aged ; Patient Compliance ; Perception ; Renal Dialysis/psychology ; Renal Insufficiency, Chronic/*psychology/therapy ; Spain ; Young Adult ; }, abstract = {AIM: To analyse the predictive value of illness representations on treatment adherence and coping strategies in a group of patients on haemodialysis.

BACKGROUND: Understanding the cognitive and emotional factors that influence adherence behaviour and coping strategies and determining their relationship to sociodemographic factors remain a challenge; meeting this challenge would encourage comprehensive patient care, thereby improving their quality of life

DESIGN: Cross-sectional study with predictive means in a sample of 135 patients on haemodialysis.

METHODS: Data collection occurred from September 2010-January 2012 and tools included the following: sociodemographic data, Illness Perception Questionnaire-Revised, the Cuestionario de Afrontamiento del Estrés and the Morisky-Green test to study adherence to treatment.

RESULTS: Being a woman, having a greater knowledge of the disease and having a poorer sense of personal control affected adherence to treatment on controlling for each factor. 'Identity', 'personal control' and 'adherence' were associated with a proactive coping strategy, whereas 'evolution' and 'gender' were related independently to avoidance coping strategies; those who believed that their illness had a chronic course were more likely to cope by avoiding the problem and this tendency was stronger among women.

CONCLUSIONS: This study provides evidence supporting the role of gender, knowledge about the disease and sense of personal control in adherence to therapeutic regimens of patients in chronic haemodialysis. The identification and characterization of patients' perception of chronic illness may represent a useful framework to influence disease outcomes such as adherence.}, } @article {pmid26688682, year = {2015}, author = {Grebić, D and Tomašić, AM}, title = {Sporadic Case of Breast Angiosarcoma as a Complication of Radiotherapy Following Breast-Conserving Surgery for Invasive Ductal Breast Cancer.}, journal = {Breast care (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {336-338}, pmid = {26688682}, issn = {1661-3791}, abstract = {BACKGROUND: Angiosarcomas are highly aggressive and malignant blood vessel tumors. Rarely, angiosarcomas develop in the breast following conservative therapy, namely radiotherapy.

CASE REPORT: A 70-year-old female patient presented with dark purple discoloration of the skin of the right breast. 6 years earlier, the patient had undergone conservative surgery for invasive ductal carcinoma of the right breast. According to the breast-conserving surgery protocol, the patient had been treated with radiotherapy to the residual breast tissue. The patient's annual mammograms and ultrasound findings were normal. The skin lesion was superficially localized mostly at the border between the upper and lower medial quadrants of the breast (between 2 and 4 o'clock) and above the areola. The borders were uneven; the dimensions were 7 cm × 4 cm. The mammogram was classified as Breast Imaging Report and Data System (BI-RADS) 2. Ultrasound examination showed a well-vascularized structure, although the etiology was unclear. A tissue biopsy revealed angiosarcoma. The patient underwent radical simplex mastectomy. Following surgery, the patient underwent chemotherapy. Tests excluded metastases for a follow-up period of 5 years.

CONCLUSION: Angiosarcomas that develop after radiotherapy following breast-conserving surgery are sporadic, but it is important to take this possible incident into consideration during treatment.}, } @article {pmid26684357, year = {2016}, author = {Dai, K and Qin, F and Zhang, H and Liu, X and Guo, C and Zhang, M and Gu, F and Fu, L and Ma, Y}, title = {Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.}, journal = {Oncotarget}, volume = {7}, number = {4}, pages = {4770-4784}, pmid = {26684357}, issn = {1949-2553}, support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; Bone Morphogenetic Protein Receptors, Type I/*metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Bridged-Ring Compounds/administration & dosage ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Taxoids/administration & dosage ; }, abstract = {Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.}, } @article {pmid26684050, year = {2016}, author = {Sanders, LM and Daigle, M}, title = {The Rightful Role of MRI after Negative Conventional Imaging in the Management of Bloody Nipple Discharge.}, journal = {The breast journal}, volume = {22}, number = {2}, pages = {209-212}, doi = {10.1111/tbj.12551}, pmid = {26684050}, issn = {1524-4741}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/surgery ; Exudates and Transudates/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammary Glands, Human/pathology/*surgery ; Middle Aged ; Nipples/diagnostic imaging/*metabolism/surgery ; Preoperative Care ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult ; }, abstract = {Nipple discharge is a frequent presenting complaint at breast clinics. Bloody nipple discharge (BND) has the highest risk of malignancy, albeit low. If mammogram and ultrasound are unrevealing, central duct excision (CDE) has been considered the gold standard in its management. Magnetic resonance imaging (MRI) has been widely confirmed as a highly sensitive test for detection of breast cancer, with an accompanying high negative predictive value. This article presents a retrospective review of patients with BND and negative conventional imaging, comparing outcome of patients who went directly to CDE without MRI to those patients who underwent preoperative MRI. Of 115 patients who underwent mammography and US alone prior to CDE, eight cancers were detected (seven ductal carcinoma in situ [DCIS] and 1 IDC, 7 mm [T1b]; incidence: 7%). Of 85 patients who underwent conventional imaging followed by MRI prior to surgery, eight cancers were detected (all DCIS; incidence: 9.4%), seven of which were identified by MRI. The one false-negative MRI had subtle findings which, in retrospect, were misinterpreted; however, a clinically apparent nipple lesion prompted surgical biopsy. Of 56 patients with a negative or benign MRI, CDE was negative for malignancy in all but that one patient. Sensitivity and specificity were 87.5%/71.4%. Positive predictive value and negative predictive value (NPV) were 24.1%/98.2%. MRI should be performed in all patients with BND and negative conventional imaging. The extremely high NPV of MRI suggests that a negative study could obviate CDE in most patients unless overriding clinical factors prevail.}, } @article {pmid26680994, year = {2016}, author = {Fan, Z and Silva, P and Gronau, I and Wang, S and Armero, AS and Schweizer, RM and Ramirez, O and Pollinger, J and Galaverni, M and Ortega Del-Vecchyo, D and Du, L and Zhang, W and Zhang, Z and Xing, J and Vilà, C and Marques-Bonet, T and Godinho, R and Yue, B and Wayne, RK}, title = {Worldwide patterns of genomic variation and admixture in gray wolves.}, journal = {Genome research}, volume = {26}, number = {2}, pages = {163-173}, pmid = {26680994}, issn = {1549-5469}, support = {R00 HG005846/HG/NHGRI NIH HHS/United States ; R00HG005846/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Dogs/*genetics ; Female ; Genome ; Hybridization, Genetic ; Male ; Markov Chains ; Models, Genetic ; Phylogeny ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Sequence Analysis, DNA ; Wolves/*genetics ; }, abstract = {The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World. However, no single wolf population is more closely related to dogs, supporting the hypothesis that dogs were derived from an extinct wolf population. All extant wolves have a surprisingly recent common ancestry and experienced a dramatic population decline beginning at least ∼30 thousand years ago (kya). We suggest this crisis was related to the colonization of Eurasia by modern human hunter-gatherers, who competed with wolves for limited prey but also domesticated them, leading to a compensatory population expansion of dogs. We found extensive admixture between dogs and wolves, with up to 25% of Eurasian wolf genomes showing signs of dog ancestry. Dogs have influenced the recent history of wolves through admixture and vice versa, potentially enhancing adaptation. Simple scenarios of dog domestication are confounded by admixture, and studies that do not take admixture into account with specific demographic models are problematic.}, } @article {pmid26679836, year = {2016}, author = {Ben-David, BM and Durham, NA and van Lieshout, PH}, title = {The Linguistic Acoustic ThreaT Effect (LATTE): Screening tool for the impact of semantic threat in speech processing after a brain injury.}, journal = {Brain injury}, volume = {30}, number = {2}, pages = {237-239}, doi = {10.3109/02699052.2015.1091506}, pmid = {26679836}, issn = {1362-301X}, mesh = {Adolescent ; Brain Injuries/*complications ; Female ; Humans ; Linguistics ; Male ; Semantics ; Speech/*physiology ; Young Adult ; }, } @article {pmid26670744, year = {2016}, author = {Sin, EI and Wong, CY and Yong, WS and Ong, KW and Madhukumar, P and Tan, VK and Thike, AA and Tan, PH and Tan, BK}, title = {Breast carcinoma and phyllodes tumour: a case series.}, journal = {Journal of clinical pathology}, volume = {69}, number = {4}, pages = {364-369}, doi = {10.1136/jclinpath-2015-203475}, pmid = {26670744}, issn = {1472-4146}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Female ; Humans ; Middle Aged ; Phyllodes Tumor/*pathology ; }, abstract = {Malignant transformation of the epithelial component of phyllodes tumours (PT) is rare and only reported in literature as sporadic cases of carcinoma associated with PTs. We report the clinicopathological characteristics of in situ and invasive carcinoma coexisting with PT in 10 patients treated in our institution over an 11-year period from 1992 to 2012. Ten patients with coexisting PT and in situ or invasive carcinoma were identified from our records. Six had carcinoma found within the PT. All were female with a median age of 47 (43-72) years. One patient had a history of PT in the same breast while another had a history of PT in the same breast as well as invasive ductal carcinoma in the contralateral breast. The rest did not have any risk factors of breast cancer. Five patients had a preoperative core needle biopsy performed with the report of a fibroepithelial lesion. The rest of the patients had surgery upfront for their breast masses. Two patients who had ER/PR positive invasive carcinoma received adjuvant hormonal therapy. Patients were followed up for a mean of 3.6 years (9 months-10 years) and all patients were alive and recurrence free. PT associated with carcinoma is rare, and we present a series of cases that add to the limited current literature. It is often difficult to detect the presence of the carcinomatous component preoperatively. Hence, close examination of resected PT specimens must be carried out to allow prompt detection of any associated carcinomas, however rare, such that adequate treatment can be given.}, } @article {pmid26670275, year = {2015}, author = {Serina, P and Riley, I and Stewart, A and Flaxman, AD and Lozano, R and Mooney, MD and Luning, R and Hernandez, B and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gamage, S and Gomez, S and Hensman, D and James, SL and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rampatige, R and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Wijesekara, N and Murray, CJ and Lopez, AD}, title = {A shortened verbal autopsy instrument for use in routine mortality surveillance systems.}, journal = {BMC medicine}, volume = {13}, number = {}, pages = {302}, pmid = {26670275}, issn = {1741-7015}, mesh = {Adult ; Cause of Death ; Child, Preschool ; Developing Countries ; *Epidemiological Monitoring ; Humans ; Infant, Newborn ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach.

METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates.

RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively.

CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.}, } @article {pmid26668534, year = {2015}, author = {Üreyen, O and Dadalı, E and Akdeniz, F and Şahin, T and Tekeli, MT and Eliyatkın, N and Postacı, H and İlhan, E}, title = {Co-existent breast and renal cancer.}, journal = {Ulusal cerrahi dergisi}, volume = {31}, number = {4}, pages = {238-240}, pmid = {26668534}, issn = {1300-0705}, abstract = {The concomitant presence of breast cancer with one or more other types of cancer such as colon, vulva, lung, larynx, liver, uterus and kidneys has been presented in the literature. However, synchronous breast and renal cancer is very uncommon. Herein we present a woman with synchronous breast and renal cancer, and review the literature. A 77-year-old post-menopausal woman was admitted to our clinic complaining of left sided breast mass. On physical examination, there was a 3 cm palpable mass in the upper outer quadrant of the left breast along with a conglomerate of lymph nodes in the left axilla. Ultrasonography and mammography showed a 3 cm solid, hypoechoic mass in the upper outer quadrant and left axillary lymphadenopathy. The tru-cut biopsy of the lesion revealed invasive ductal carcinoma. The bone scintigraphy, thoracic and cranial computerized tomographies were normal. The abdominal computerized tomography identified a 3×3 cm solid renal mass with heterogeneous contrast enhancement in the posterior segment of the lower pole, which was suspicious for renal cell carcinoma. Breast conserving surgery and axillary lymph node dissection was performed, and the pathology specimen demonstrated invasive ductal carcinoma. The patient was discharged on postoperative day 5. Three weeks later partial nephrectomy was performed by urology department for the solid renal mass, and the pathology result showed clear cell-renal carcinoma with Fuhrman grade 3. The patient is being followed-up for renal carcinoma, and underwent radiotherapy for breast cancer. Hormonotherapy for breast cancer is still continuing.}, } @article {pmid26663655, year = {2016}, author = {Karan, B and Pourbagher, A and Torun, N}, title = {Diffusion-weighted imaging and (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer: Correlation of the apparent diffusion coefficient and maximum standardized uptake values with prognostic factors.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {43}, number = {6}, pages = {1434-1444}, doi = {10.1002/jmri.25112}, pmid = {26663655}, issn = {1522-2586}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Mammography/methods ; Middle Aged ; Positron Emission Tomography Computed Tomography/*methods ; Prognosis ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To evaluate the correlations between the apparent diffusion coefficient (ADC) value and the standardized uptake value (SUV) with prognostic factors in breast cancer.

MATERIALS AND METHODS: Seventy women with invasive breast cancer (56 cases of invasive ductal carcinoma, four of mixed ductal and lobular invasive carcinoma, three of lobular invasive carcinoma, two of micropapillary carcinoma, and one each of mixed ductal and mucinous carcinoma, mucinous carcinoma, medullary carcinoma, metaplastic carcinoma, and tubular carcinoma) were included in this study. All patients underwent presurgical breast magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) at 1.5T and whole-body (18) F-fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET) / computed tomography (CT). For all invasive breast cancers and invasive ductal carcinomas, we assessed the relationships among ADC, SUV, and pathological prognostic factors.

RESULTS: Both the median ADC value and maximum SUV (SUVmax) were significantly associated with vascular invasion (P = 0.008 and P = 0.026, respectively). SUVmax was also significantly correlated with tumor size (P = 0.001), histological grade (P = 0.001), lymph node status (P = 0.0015), estrogen receptor status (P = 0.010), and human epidermal growth factor receptor 2 status (P = 0.020), whereas ADC values were not. The correlation between the ADC and SUVmax was not significant (P = 0.356; R = -0.112). Mucinous carcinoma showed high ADC and relatively low SUVmax. Medullary carcinoma showed low ADC and high SUVmax. When we evaluated the relationships among ADC, SUVmax, and prognostic factors in the 56 invasive ductal carcinomas, our statistical results were not significantly changed, except SUVmax was also significantly associated with progesterone receptor status (P = 0.034), but not lymph node status.

CONCLUSION: SUVmax may be valuable for predicting the prognosis of breast cancer. Both ADC and SUVmax are useful to predict vascular invasion. J. Magn. Reson. Imaging 2016;43:1434-1444.}, } @article {pmid26657376, year = {2016}, author = {Adak, P and Sahu, R and Elumalai, SP}, title = {Development of emission factors for motorcycles and shared auto-rickshaws using real-world driving cycle for a typical Indian city.}, journal = {The Science of the total environment}, volume = {544}, number = {}, pages = {299-308}, doi = {10.1016/j.scitotenv.2015.11.099}, pmid = {26657376}, issn = {1879-1026}, mesh = {Air Pollutants/*analysis ; Air Pollution/*statistics & numerical data ; Cities ; Environmental Monitoring/*methods ; India ; Models, Statistical ; Motorcycles/*statistics & numerical data ; Vehicle Emissions/*analysis ; }, abstract = {Vehicular emission is one of the most important contributors of urban air pollution. To quantify the impact of traffic on urban air quality, it is necessary to quantify vehicular emission. In many cities of India, such as Dhanbad, shared auto-rickshaw is the pre-dominant mode of transportation. Indian Driving Cycle (IDC) and Modified Indian Driving Cycle (MIDC) are used for emission testing of motorcycles, shared auto-rickshaws and passenger cars in India for regulatory purposes. IDC used for motorcycles and shared auto-rickshaws does not recognize the difference in two vehicle classes in terms of driving pattern. In real world, shared auto-rickshaws, behave differently than motorcycles. To quantify the impact of shared auto-rickshaws on urban air quality accurately, emission factors (EFs) are required to derive from real-world driving cycles (DCs). In heterogeneous traffic, vehicles of one class affect the behavior of vehicles of other classes. To estimate the emissions from different vehicle classes accurately, EFs for motorcycles and passenger cars are also required to be revised. In this study, real-world DCs were developed for motorcycles, shared auto-rickshaws and passenger cars in Dhanbad. Developed DCs were used to calculate EFs for respective classes. Shared auto-rickshaws were found to have the highest deviation from EFs derived using IDC.}, } @article {pmid26656588, year = {2015}, author = {Zhang, ZQ and Han, YZ and Nian, Q and Chen, G and Cui, SQ and Wang, XY}, title = {Tumor Invasiveness, Not Lymphangiogenesis, Is Correlated with Lymph Node Metastasis and Unfavorable Prognosis in Young Breast Cancer Patients (≤35 Years).}, journal = {PloS one}, volume = {10}, number = {12}, pages = {e0144376}, pmid = {26656588}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/enzymology/*pathology ; Cell Proliferation ; Female ; Humans ; Kaplan-Meier Estimate ; *Lymphangiogenesis ; Lymphatic Metastasis/*pathology ; Matrix Metalloproteinase 9/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Vascular Endothelial Growth Factor C/metabolism ; Vesicular Transport Proteins/metabolism ; }, abstract = {The morbidity rate of breast cancer is on the rise, and the age of onset appears to be trending toward a young age. Breast cancer in young women (BCYW) has a number of distinctive features that differ from breast cancer in middle-aged or elderly women (BCMEW). Lymphatic metastasis plays an important role in the spread of BCYW; however, the mechanisms of lymph node metastasis (LNM) in BCYW are not clear. This study aimed to investigate the mechanism of lymphatic metastasis in BCYW and to evaluate the relationships between lymphangiogenesis, the expression of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) expression, clinicopathological characteristics, and prognosis. Using immunohistochemistry, MMP-9, VEGF-C and the level of lymphatic microvessel density (LMVD) were analyzed in 106 cases of breast invasive ductal carcinoma and 20 cases of breast proliferative lesions. Compared with BCMEW, BCYW had higher MMP-9 expression, higher LNM, and more adverse prognoses. In BCYW, high MMP-9 expression was positively correlated with LNM and impaired survival time. However, in BCMEW, MMP-9 expression was not correlated with LNM or survival time. In addition, high VEGF-C expression was positively correlated with a high level of LMVD in both BCYW and BCMEW. Nevertheless, a high level of LMVD was not correlated with LNM or survival time in the two groups. More importantly, univariate and multivariate survival analysis showed that MMP-9 expression and LNM were independent prognostic factors in BCYW. Our present study indicates that lymphangiogenesis induced by VEGF-C is augmented in breast cancer; however, a higher level of lymphangiogenesis has no significant impact on LNM or survival time. We suggest that tumor invasiveness, rather than lymphangiogenesis, plays an important role in LNM among BCYW. Moreover, MMP-9 and LNM were independent prognostic factors for BCYW.}, } @article {pmid26652590, year = {2015}, author = {Andersen, TE and Lahav, Y and Defrin, R and Mikulincer, M and Solomon, Z}, title = {Attachment security and pain--The disrupting effect of captivity and PTSS.}, journal = {Journal of psychosomatic research}, volume = {79}, number = {6}, pages = {471-476}, doi = {10.1016/j.jpsychores.2015.10.008}, pmid = {26652590}, issn = {1879-1360}, mesh = {*Adaptation, Psychological ; Adult ; Humans ; Male ; Object Attachment ; Pain/*psychology ; Prisoners/psychology ; Self Report ; Stress Disorders, Post-Traumatic/*psychology ; Survivors ; Veterans/*psychology ; Warfare ; }, abstract = {The present study assesses the possible disruption effect of posttraumatic stress symptoms (PTSS) with regard to the protective role of attachment on pain, among ex-POWs. While secure attachment seems to serve as a buffer, decreasing the perception of pain, this function may be disrupted by PTSS. The study sample included 104 subjects who were combat veterans of the 1973 Yom Kippur War comprising of 60 male ex-prisoners of war (ex-POWs) and 44 comparable male combat veterans. Both attachment and pain were investigated experimentally in the laboratory and via questionnaires. We found that ex-POWs showed higher levels of clinical pain and attachment insecurities compared to controls. Moreover, attachment avoidance and soothing effect of attachment (SEA) were both associated with lower levels of clinical pain. Most importantly, PTSS moderated the associations between attachment and pain, as well as the mediation role of attachment between captivity and pain. The results imply that although attachment can be an important resource for coping with pain, it can be severely disrupted by PTSS among trauma survivors.}, } @article {pmid26652003, year = {2015}, author = {Hein, AM and Rosenthal, SB and Hagstrom, GI and Berdahl, A and Torney, CJ and Couzin, ID}, title = {The evolution of distributed sensing and collective computation in animal populations.}, journal = {eLife}, volume = {4}, number = {}, pages = {e10955}, pmid = {26652003}, issn = {2050-084X}, mesh = {Animals ; *Behavior, Animal ; Biological Evolution ; Fishes/*physiology ; Models, Biological ; *Social Behavior ; }, abstract = {Many animal groups exhibit rapid, coordinated collective motion. Yet, the evolutionary forces that cause such collective responses to evolve are poorly understood. Here, we develop analytical methods and evolutionary simulations based on experimental data from schooling fish. We use these methods to investigate how populations evolve within unpredictable, time-varying resource environments. We show that populations evolve toward a distinctive regime in behavioral phenotype space, where small responses of individuals to local environmental cues cause spontaneous changes in the collective state of groups. These changes resemble phase transitions in physical systems. Through these transitions, individuals evolve the emergent capacity to sense and respond to resource gradients (i.e. individuals perceive gradients via social interactions, rather than sensing gradients directly), and to allocate themselves among distinct, distant resource patches. Our results yield new insight into how natural selection, acting on selfish individuals, results in the highly effective collective responses evident in nature.}, } @article {pmid26648741, year = {2015}, author = {Sun, HT and Wen, X and Han, T and Liu, ZH and Li, SB and Wang, JG and Liu, XP}, title = {Expression of CPEB4 in invasive ductal breast carcinoma and its prognostic significance.}, journal = {OncoTargets and therapy}, volume = {8}, number = {}, pages = {3499-3506}, pmid = {26648741}, issn = {1178-6930}, abstract = {AIMS: Cytoplasmic polyadenylation element binding proteins (CPEBs) are RNA-binding proteins that regulate translation by inducing cytoplasmic polyadenylation. CPEB4 has been reported in association with tumor growth, vascularization, and invasion in several cancers. To date, the expression of CPEB4 with clinical prognosis of breast cancer was never reported before. We aim to investigate the expression of CPEB4 and its prognostic significance in invasive ductal breast carcinoma.

METHODS: Immunohistochemical staining of CPEB4 and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor was performed in 107 invasive ductal carcinoma (IDC) samples, and prognostic significance was evaluated.

RESULTS: High expression of CPEB4 was observed in 48.6% of IDC samples. Elevated CPEB4 expression was possibly related to increased histological grading (P=0.037) and N stage (P<0.001). Patients with high expression of CPEB4 showed shorter overall survival (P=0.001). High CPEB4 expression was an independent prognostic factor for overall survival (P=0.022, hazard ratio =4.344, 95% confidence interval =1.235-15.283).

CONCLUSION: High CPEB4 expression is associated with increased histological grading and N stage, and it can serve as an independent prognostic factor in IDC.}, } @article {pmid26644140, year = {2015}, author = {Serina, P and Riley, I and Stewart, A and James, SL and Flaxman, AD and Lozano, R and Hernandez, B and Mooney, MD and Luning, R and Black, R and Ahuja, R and Alam, N and Alam, SS and Ali, SM and Atkinson, C and Baqui, AH and Chowdhury, HR and Dandona, L and Dandona, R and Dantzer, E and Darmstadt, GL and Das, V and Dhingra, U and Dutta, A and Fawzi, W and Freeman, M and Gomez, S and Gouda, HN and Joshi, R and Kalter, HD and Kumar, A and Kumar, V and Lucero, M and Maraga, S and Mehta, S and Neal, B and Ohno, SL and Phillips, D and Pierce, K and Prasad, R and Praveen, D and Premji, Z and Ramirez-Villalobos, D and Rarau, P and Remolador, H and Romero, M and Said, M and Sanvictores, D and Sazawal, S and Streatfield, PK and Tallo, V and Vadhatpour, A and Vano, M and Murray, CJ and Lopez, AD}, title = {Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.}, journal = {BMC medicine}, volume = {13}, number = {}, pages = {291}, pmid = {26644140}, issn = {1741-7015}, mesh = {Autopsy/*methods ; *Cause of Death ; Female ; Humans ; Male ; }, abstract = {BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method.

METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database.

RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE.

CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.}, } @article {pmid26643230, year = {2015}, author = {Street, P and Thompson, J and Bailey, M}, title = {Management of urinary catheters following hip fracture.}, journal = {Australasian journal on ageing}, volume = {34}, number = {4}, pages = {241-246}, doi = {10.1111/ajag.12166}, pmid = {26643230}, issn = {1741-6612}, mesh = {Aged ; Aged, 80 and over ; *Catheters, Indwelling ; Chi-Square Distribution ; Dementia/complications ; Device Removal ; Female ; Guideline Adherence ; *Health Services for the Aged/standards ; Hip Fractures/complications/diagnosis/*therapy ; Humans ; Logistic Models ; Male ; Medical Audit ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Patient Discharge ; Practice Guidelines as Topic ; Prognosis ; Residential Facilities ; Retrospective Studies ; Risk Factors ; Urinary Catheterization/adverse effects/*instrumentation/standards ; *Urinary Catheters ; }, abstract = {AIM: To examine current practices and factors associated with outcomes of urinary catheter removal ('trial of void' or TOV) in patients following hip fracture.

METHOD: Retrospective file audit of patients discharged over a three-year period with a diagnosis of recent hip fracture.

RESULTS: There were 133 TOVs in 310 patients. Of the 78 TOVs occurring in the aged care rehabilitation hospital, 50% were successful. Adherence to the hospital's TOV guideline was documented infrequently. TOV outcome was not related to interval since catheter insertion, constipation or inability to mobilise. Multivariate analysis showed that dementia was independently associated with the presence of an in-dwelling catheter (IDC) on discharge and that patients discharged with an IDC had a higher probability of residential care placement.

CONCLUSIONS: Practices in managing TOVs are inconsistent. No potentially modifiable predictors of TOV success were identified. The presence of an IDC has implications for discharge destination.}, } @article {pmid26643011, year = {2016}, author = {Torabi-Nezhad, S and Malekmakan, L and Mashayekhi, M and Daneshian, A}, title = {Histopathological features of intra-ductal carcinoma of prostatic and high grade prostatic intraepithelialneoplasia and correlation with PTEN and P63.}, journal = {The Prostate}, volume = {76}, number = {4}, pages = {394-401}, doi = {10.1002/pros.23130}, pmid = {26643011}, issn = {1097-0045}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal/*pathology ; Humans ; Immunohistochemistry ; Iran ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; PTEN Phosphohydrolase/*analysis ; Prognosis ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; Transcription Factors/analysis ; Tumor Suppressor Proteins/analysis ; }, abstract = {BACKGROUND: The main morphologic differential diagnosis of intra-ductal carcinoma of prostate (IDC-P) is high grade prostatic intraepithelialneoplasia (HGPIN). Since IDC-P, unlike PIN, was strongly correlated with aggressive prostate cancer, differentiation of these is too necessary. So we evaluated immunohistopathological patterns and the prognostic factors of IDC-P and HGPIN, in radical prostatectomy samples.

METHODS: We evaluated 250 radical prostatectomy and detected 210 cases of prostatic adenocarcinoma without IDC-P foci, 40 cases with adenocarcinoma concomitant IDC-P, and 40 cases HGPIN; therefore, we evaluated immunohistopathological criteria in these groups. Data were analyzed using SPSS and P-value <0.05 was considered as the statistical significant level.

RESULTS: PSA level was significantly higher in IDC-P compared with non-IDC-P patients (15.7 ± 3.1 vs. 10.2 ± 4.3, P = 0.041). All pathological and morphologic features, also invasions factors were higher in IDC-P compared to non-IDC-P groups (P < 0.001). P63 was positive expressed in all IDC-P and HGPIN specimen. PTEN protein was diffusely expressed in the cytoplasm of all HGPIN but in 4 (11.1%) of IDC-P. PTEN and P63 were negative in adenocarcinoma foci.

CONCLUSION: We found that IDC-P had a unique histoclinical feature and was strongly associated with poor prognostic factors. Diagnosis and report of IDC-P should be considered in all prostate specimens. Also, we recommend PTEN IHC application for differentiated IDC-P from HGPIN in biopsies.}, } @article {pmid26642819, year = {2016}, author = {Isidro, A and Díez-Santacoloma, I and Bagot, J and Milla, L and Gallart, A}, title = {[A sarcophagus with a surprise: computed tomography of a mummy from the Late Period of ancient Egypt].}, journal = {Radiologia}, volume = {58}, number = {1}, pages = {64-71}, doi = {10.1016/j.rx.2015.09.007}, pmid = {26642819}, issn = {1578-178X}, mesh = {Egypt ; Female ; Humans ; Mummies/*diagnostic imaging ; *Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Diagnostic imaging techniques, at present especially computed tomography (CT), have become the most important noninvasive method for the study of mummies because they enable high resolution images and three-dimensional reconstructions without damaging the mummified subject. We present a sarcophagus with a mummy hidden inside that was acquired by a gallery in Barcelona.

MATERIAL AND METHODS: The sarcophagus and mummy were examined by CT at the Hospital Universitari Sagrat Cor in Barcelona. A flexible clamp was used to obtain tissue samples for further study.

RESULTS: The results showed the presence of an anatomically intact female human subject albeit with a destructured thorax and upper abdomen. Various metal objects were detected, corresponding to amulets, artificial eyes, and an external wooden brace.

CONCLUSION: CT is an excellent noninvasive imaging technique for the detailed study of mummies, as it enables not only the anatomic identification of the mummified subject but also the obtainment of tissue samples for complementary analyses. The description of these findings enables us to know the major radiologic landmarks for the paleopathologic study of mummies.}, } @article {pmid26642762, year = {2016}, author = {Pendharkar, N and Gajbhiye, A and Taunk, K and RoyChoudhury, S and Dhali, S and Seal, S and Mane, A and Abhang, S and Santra, MK and Chaudhury, K and Rapole, S}, title = {Quantitative tissue proteomic investigation of invasive ductal carcinoma of breast with luminal B HER2 positive and HER2 enriched subtypes towards potential diagnostic and therapeutic biomarkers.}, journal = {Journal of proteomics}, volume = {132}, number = {}, pages = {112-130}, doi = {10.1016/j.jprot.2015.11.024}, pmid = {26642762}, issn = {1876-7737}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/therapy ; Carcinoma, Ductal, Breast/diagnosis/*metabolism/therapy ; Endoplasmic Reticulum Chaperone BiP ; Female ; Humans ; Middle Aged ; Molecular Targeted Therapy/methods ; Neoplasm Proteins/*metabolism ; Proteome/*metabolism ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Worldwide, breast cancer is one of the frequently diagnosed cancers in women with high mortality if not diagnosed at early stage. Although biomarker discoveries through various proteomic approaches have been studied in breast cancer, a limited number of studies have explored the invasive ductal carcinoma with Luminal B HER2 positive (LB) and HER2 enriched (HE) subtypes. The present study employed the complementary quantitative proteomic approaches to find a panel of markers that could discriminate LB and HE subtypes as well as early (ES) and late stages (LS) of these subtypes. A total of 67 and 68 differentially expressed proteins were identified by DIGE for the subtype and stage wise categories, respectively. Multivariate statistical analysis was employed to identify the set of most significant proteins, which could discriminate between these two subtypes and also early and late stages under study. Immunoblotting and MRM based validation in a separate cohort of samples confirmed that panel of biosignatures for LB are APOA1, GELS, HS90B, EF1A1, NHRF1 and PRDX3 and for HE are PRDX1, CATD, CALR, ATPB and CH60. For the diagnosis of early and late stages the potential markers are TPM4, CATD, PRDX3, ANXA3, HSPB1 and CALR, TRFE, GELS, CH60, CAPG, NHRF1, 1433G, GRP78 respectively.}, } @article {pmid26630832, year = {2015}, author = {Loewen, AH and Schilling, SD and Milroy, M and Villanueva, ML}, title = {Case Report: Hormone Receptor Positive, HER2/neu Negative Inflammatory Breast Cancer in a Male Patient.}, journal = {South Dakota medicine : the journal of the South Dakota State Medical Association}, volume = {68}, number = {10}, pages = {435-7, 439-40}, pmid = {26630832}, issn = {0038-3317}, mesh = {Breast Neoplasms, Male/*diagnosis/metabolism ; Humans ; Inflammatory Breast Neoplasms/*diagnosis/metabolism ; Male ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/*biosynthesis ; Receptors, Progesterone/*biosynthesis ; }, abstract = {Inflammatory breast cancer is a rare and aggressive disease found almost exclusively in women. We present a case of a 51-year-old male with inflammatory breast carcinoma. The patient presented with a mass measuring roughly 7 cm with overlying erythema, peau d'orange appearance, and prominent nipple retraction. Core biopsy analysis demonstrated estrogen and progesterone receptor positive, HER2/neu receptor negative invasive ductal carcinoma. A PET scan revealed contralateral supraclavicular lymph node metastasis. The patient refused chemotherapy and radiation and was not a surgical candidate. Ultimately he opted for therapy with strictly an aromatase inhibitor. Most recent follow-up at 12 months demonstrated improvement of metastatic lesions on PET scan. Local progression of disease was noted on physical exam and the patient decided to add everolimus and radiation therapy while continuing an aromatase inhibitor. Retrospective studies have demonstrated increased survival of inflammatory breast cancer diagnosed in women with the utilization of neoadjuvant chemotherapy, surgical excision, and radiation therapy. Unfortunately, due to the rarity of the disease, no specific optimal treatment guidelines have been established for men diagnosed with this disease.}, } @article {pmid26628432, year = {2016}, author = {Kim, YS and Chang, JM and Moon, HG and Lee, J and Shin, SU and Moon, WK}, title = {Residual Mammographic Microcalcifications and Enhancing Lesions on MRI After Neoadjuvant Systemic Chemotherapy for Locally Advanced Breast Cancer: Correlation with Histopathologic Residual Tumor Size.}, journal = {Annals of surgical oncology}, volume = {23}, number = {4}, pages = {1135-1142}, doi = {10.1245/s10434-015-4993-2}, pmid = {26628432}, issn = {1534-4681}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Calcinosis/chemically induced/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/*diagnosis/diagnostic imaging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; }, abstract = {PURPOSE: To evaluate the accuracy of residual microcalcifications on mammogram (MG) in predicting the extent of the residual tumor after neoadjuvant systemic treatment (NST) in patients with locally advanced breast cancer and to evaluate factors affecting the accuracy of MG microcalcifications using magnetic resonance imaging (MRI) as a reference.

METHODS: The patients who underwent NST and showed suspicious microcalcifications on MG comprised our study population. Clinicopathologic and imaging (MG, MRI) findings were investigated. Agreement between image findings and pathology was assessed and factors affecting the discrepancy were analyzed.

RESULTS: Among 207 patients, 196 had residual invasive ductal carcinoma or ductal carcinoma-in-situ (mean size, 3.78 cm). The overall agreement of residual microcalcifications on MG predicting residual tumor extents was lower than MRI in all tumor subtypes (intraclass correlation coefficient [ICC] = 0.368 and 0.723, p < 0.0001). The agreement of residual MG microcalcifications and pathology was highest in HR(+)/HER2(+) tumors and lowest in the triple-negative tumors (ICC = 0.417 and 0.205, respectively). Multivariate linear regression analysis revealed that a size discrepancy between microcalcifications and histopathology was correlated with molecular subtype (p = 0.005). In HR(+)/HER2(-) and triple-negative subtypes, the mean extents of residual microcalcification were smaller than residual cancer, and overestimation of tumor extent was more frequent in HR(+)/HER2(+) and HR(-)/HER2(+) tumors.

CONCLUSIONS: The extent of microcalcifications on MG after NST showed an overall lower correlation with the extent of the pathologic residual tumor than enhancing lesions on MRI. The accuracy of residual tumor evaluation after NST with MG and MRI is affected by their molecular subtype.}, } @article {pmid26628318, year = {2016}, author = {Frey, JD and Alperovich, M and Kim, JC and Axelrod, DM and Shapiro, RL and Choi, M and Schnabel, FR and Karp, NS and Guth, AA}, title = {Oncologic outcomes after nipple-sparing mastectomy: A single-institution experience.}, journal = {Journal of surgical oncology}, volume = {113}, number = {1}, pages = {8-11}, doi = {10.1002/jso.24097}, pmid = {26628318}, issn = {1096-9098}, mesh = {Adult ; Body Mass Index ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/surgery ; Carcinoma, Intraductal, Noninfiltrating/surgery ; Female ; Humans ; Mammaplasty/adverse effects ; Mastectomy/*methods ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/prevention & control ; Neoplasm Staging ; New York/epidemiology ; *Nipples ; Quality of Life ; Treatment Outcome ; }, abstract = {INTRODUCTION: Long-term oncologic outcomes in nipple-sparing mastectomy (NSM) continue to be defined. Rates of locoregional recurrence for skin-sparing mastectomy (SSM) and NSM in the literature range from 0% to 14.3%. We investigated the outcomes of NSM at our institution.

METHODS: Patients undergoing NSM at our institution from 2006 to 2014 were identified and outcomes were analyzed.

RESULTS: From 2006 to 2014, 319 patients (555 breasts) underwent NSM. One-hundered and fourty-one patients (237 breasts) had long-term follow-up available. Average patient age and BMI were 47.78 and 24.63. Eighty-four percent of patients underwent mastectomy primarily for a therapeutic indication. Average tumor size was 1.50 cm with the most common histologic type being invasive ductal carcinoma (62.7%) followed by DCIS (23.7%). Average patient follow-up was 30.73 months. There was one (0.8%) incidence of ipsilateral chest-wall recurrence. There were 0.37 complications per patient.

CONCLUSIONS: We examined our institutional outcomes with NSM and found a locoregional recurrence rate of 0.8% with no nipple-areolar complex recurrence. This rate is lower than published rates for both NSM and SSM.}, } @article {pmid26622803, year = {2015}, author = {Zhang, J and Zhang, H and Xu, X and Wang, M and Yu, Z}, title = {Comparative genomic hybridization analysis of invasive ductal breast carcinomas in the Chinese population.}, journal = {Oncology letters}, volume = {10}, number = {4}, pages = {2100-2106}, pmid = {26622803}, issn = {1792-1074}, abstract = {Breast cancer is the most common malignancy in Chinese women. The aim of the present study was to investigate the genetic alterations that occur in breast cancer cells in Chinese women. Comparative genomic hybridization (CGH) analysis was performed on 34 tumors obtained from patients with primary invasive ductal breast carcinoma (IDC). Recurrent genetic alterations in breast cancer include gains on chromosomes 1q (59%), 16p (50%), 17q (44%), 8q (38%), 11q (32%), 20q (32%), 1p (24%), 20p (24%), 19q (21%) and 19p (18%). Losses are common on chromosomes 6q (15%), 8p (12%), 18 (12%), 4q (9%), X (9%) and 17p (9%). In the present study, high-level amplifications were observed on chromosomes 1q32, 8p, 11q13, 17q and 20q. Overall, the chromosomal DNA gains observed were consistent with the changes reported in Caucasian populations. However, the incidence of chromosomal DNA loss was lower in the present study compared with the incidence reported in the literature. The present results demonstrate the pattern of chromosomal imbalances in the invasive ductal breast carcinomas of Chinese females.}, } @article {pmid26622750, year = {2015}, author = {Zhang, S and Yu, YH and Qu, W and Zhang, Y and Li, J}, title = {Diagnosis and treatment of accessory breast cancer in 11 patients.}, journal = {Oncology letters}, volume = {10}, number = {3}, pages = {1783-1788}, pmid = {26622750}, issn = {1792-1074}, abstract = {The present study aimed to investigate the clinical characteristics, diagnosis and treatment of accessory breast cancer, and contribute valuable information regarding this rare tumour to the current literature, ultimately facilitating the development of improved treatment strategies. The present study reported the cases of 11 patients with accessory breast cancer. The patients with accessory breast cancer were admitted between January 2002 and June 2014, and the patient records were retrospectively analysed. All patients presented with a tumour that was localised in the axilla. Out of these patients, there were 8 patients with invasive ductal carcinoma and 3 patients with invasive lobular carcinoma. The follow-up periods for patients ranged between 4 and 54 months. Out of the 5 patients that experienced neoplasm metastases, 4 patients succumbed to the disease. In total, 6 patients remain alive with no evidence of disease. Accessory breast cancer is a progressive tumour, and long-term follow-up is required. A comprehensive treatment strategy may be an effective treatment option for patients; however, the optimal time at which to commence chemotherapy and the role of combined radiotherapy and endocrine therapy require additional investigation.}, } @article {pmid26622700, year = {2015}, author = {Zheng, H and Chen, J and Wu, X and Jin, L and Qi, C}, title = {Bilateral breast cancer with a unilateral carcinoma within a fibroadenoma: A case report.}, journal = {Oncology letters}, volume = {10}, number = {3}, pages = {1513-1516}, pmid = {26622700}, issn = {1792-1074}, abstract = {Fibroadenomas are a type of benign tumor that occur in young women below the age of 35 years old. The tumors are the second most common type of tumor after fibrocystic disease. The chance of carcinoma arising in a fibroadenoma is extremely low. To date, <130 such cases have been reported. Previous studies have reported that fibroadenomas can evolve into a number of different types of malignancy. The present study is the first to describe a case of bilateral primary breast cancer with a unilateral invasive ductal carcinoma within a fibroadenoma. The current study presents a case of a 48-year-old female who presented with 2 stiff lumps on bilateral breasts, diagnosed as bilateral breast carcinoma, with a unilateral invasive ductal carcinoma within a fibroadenoma in the right breast. The patient underwent a bilateral mastectomy and subsequently received 4 cycles of chemotherapy (epirubicin, 60 mg/m[2] and cyclophosphamide, 600 mg/m[2]) every 21 days, followed by 4 cycles of docetaxel chemotherapy (100 mg/m[2]) every 21 days. The patient then received maintenance endocrine therapy (tamoxifen, 20 mg, twice daily) for 19 months. The patient was followed up every 3 months, and at the last follow-up examination in May 2015, the patient exhibited no signs of recurrence.}, } @article {pmid26621543, year = {2016}, author = {Ruszczyk, M and Zirpoli, G and Kumar, S and Bandera, EV and Bovbjerg, DH and Jandorf, L and Khoury, T and Hwang, H and Ciupak, G and Pawlish, K and Schedin, P and Masso-Welch, P and Ambrosone, CB and Hong, CC}, title = {Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses.}, journal = {Cancer causes & control : CCC}, volume = {27}, number = {2}, pages = {183-198}, pmid = {26621543}, issn = {1573-7225}, support = {U58 DP003931/DP/NCCDPHP CDC HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; 5U58DP003931-02/DP/NCCDPHP CDC HHS/United States ; P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA169175/CA/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; K22 CA138563/CA/NCI NIH HHS/United States ; N01PC-2013-00021/PC/NCI NIH HHS/United States ; R03 CA17106/CA/NCI NIH HHS/United States ; R03 CA171061/CA/NCI NIH HHS/United States ; R01 CA185623/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Feeding/*statistics & numerical data ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/pathology ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Middle Aged ; Multivariate Analysis ; Obesity/*epidemiology ; Odds Ratio ; Overweight/epidemiology ; *Reproductive History ; Risk Factors ; }, abstract = {PURPOSE: Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS.

METHODS: We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n = 650) or pure IDC (n = 181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression.

RESULTS: Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk of pure IDC was lower in women with body mass index (BMI) 25 to <30 [odds ratio (OR) 0.66; 95 % confidence interval (CI) 0.35-1.23] and BMI ≥ 30 (OR 0.33; 95 % CI 0.18-0.67) compared to women with BMI < 25, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR 0.55; 95 % CI 0.32-0.94) or longer (OR 0.47; 95 % CI 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed.

CONCLUSIONS: Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the developmental patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS.}, } @article {pmid26619027, year = {2015}, author = {Bomeisl, PE and Thompson, CL and Harris, LN and Gilmore, HL}, title = {Comparison of Oncotype DX Recurrence Score by Histologic Types of Breast Carcinoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {139}, number = {12}, pages = {1546-1549}, doi = {10.5858/arpa.2014-0557-OA}, pmid = {26619027}, issn = {1543-2165}, mesh = {Adenocarcinoma/*pathology ; Adenocarcinoma, Mucinous/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*pathology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Risk ; }, abstract = {CONTEXT: Oncotype DX (ODX) is a widely used commercial assay that estimates the risk of distant recurrence and may predict the benefit of chemotherapy in a subset of breast cancers. Some studies have shown the ability to predict Oncotype DX recurrence score (ODXRS), based on routinely reported pathologic features; however, there are limited data correlating specific histologic type of breast cancer to ODXRS.

OBJECTIVE: To compare ODXRS to specific histologic types of breast cancer.

DESIGN: One hundred eighty-four cases were sent for ODXRS testing and the results were compared with histologic type and grade.

RESULTS: The highest average ODXRS was seen in invasive ductal carcinoma with micropapillary features (29) followed by invasive ductal carcinoma not otherwise specified (mean = 19.4, SD = 11.6), invasive mucinous carcinoma (mean = 17.2, SD = 5.9), invasive lobular carcinoma (mean = 15.7, SD = 7.2), mixed ductal and lobular carcinoma (mean = 14.1, SD = 7.7), tubular carcinoma (10.0), and mixed ductal and mucinous carcinoma (mean = 8.0, SD = 4.2). Most tumors that had a high ODXRS were grade 3 invasive ductal carcinoma, representing 13 of a total of 20 cases (65%). Interestingly, 3 of the 4 cases of pure invasive mucinous carcinoma had an intermediate ODXRS.

CONCLUSIONS: Although the numbers are small, our findings raise further awareness of the significance between histologic type and grade, and RS in breast cancer. In some special histologic types of breast cancer, particularly those considered to follow either an excellent or poor clinical course by histology alone, it is unclear whether the ODXRS results are as meaningful as in carcinomas of no special type. Further investigation with higher numbers and outcome data is needed.}, } @article {pmid26617852, year = {2015}, author = {Chen, Y and Song, J and Jiang, Y and Yu, C and Ma, Z}, title = {Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {9}, pages = {11287-11295}, pmid = {26617852}, issn = {1936-2625}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/immunology/pathology/surgery ; CD24 Antigen/*analysis ; Carcinoma, Ductal, Breast/*drug therapy/*immunology/secondary/surgery ; Chemotherapy, Adjuvant ; Child ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Phenotype ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Cells with unique phenotypes and stem cell-like properties have been found to exist in breast cancer. The aim of the present study was to study the relationship of CD24, CD44, CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes' with clinico-pathological features, chemotherapy response and with prognosis.

METHODS: The study included paraffin-embedded tissues of 140 primary and secondary invasive ductal carcinoma samples. All the patients received routine chemotherapy. Expression of CD24, CD44, ER, PR, and Her2 were assayed immunohistochemically. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low), CD44(+)/CD24 (+), CD44(-)/CD24(-) and CD44(-)/CD24(+) cells. The association between the proportions of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) and clinicopathological features, chemotherapy response and with prognosis of these patients was evaluated.

RESULTS: CD24 expression was not significantly associated with tumor characteristics, but was significantly associated with poor prognostic variables including ER-, PR-, HER2(+) and triple negative (TN) phenotype; There was no association of CD44 with nodal status, age or HER2 expression. In the correlation analysis, CD24 expression was positively associated with chemotherapy response (P = 0.018), however, CD44 expression was not associated with pathological response to chemotherapy When both markers are considered, the CD44(+)/CD24(-) phenotype had the poor prognosis. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement, recurrent or metastatic tumors and ER/PR status. High CD44(+)/CD24(-) phenotype had poor response to chemotherapy. The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 19.8 ± 2.6 months and 31.7 ± 4.2 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 33.5 ± 2.8 months and 51.4 ± 3.9 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS. However, the CD44(-)/CD24(+), CD44(+)/CD24(+), CD44(-)/CD24 (-) phenotype had no relation with prognosis.

CONCLUSION: There was significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor metastasis, prognosis and chemotherapy response. The CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.}, } @article {pmid26617687, year = {2015}, author = {Deger, A and Ozyigit, F and Arik, O and Ekici, F and Cinkaya, A and Tayfur, M and Deger, H}, title = {Association between well-known histopathological criteria and overall survival in invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {9}, pages = {9772-9781}, pmid = {26617687}, issn = {1936-2625}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/*mortality/*pathology ; Female ; Humans ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; }, abstract = {UNLABELLED: We investigated the effect of clinical features and well-known histomorphological parameters on survival of breast cancer.

MATERIAL AND METHODS: 44 patients with invasive ductal carcinoma were included in this study. We investigated the effect of age, breast cancer location (right/left), histological grade, largest diameter of the tumor, lymphovascular and perineural invasion on patient survival. IBM SPSS (Statistical Package for Social Sciences) 20 program was used for statistics. Cox proportional hazard regression model for survival analysis, log-log plot, life function graphs were used. Results were 95% confidence interval, significance (P < 0.05).

RESULTS: In univariate analysis, the left breast localization, high histological grade, large tumor size, lymphovascular invasion, perineural invasion has been shown that reduced the overall survival (P < 0.05). In multivariate analysis, only high histological grade, large tumor size and perineural invasion were identified as parameters negatively associated with patient survival (P < 0.05). On univariate and multivariate analysis, age was not associated with survival.

CONCLUSION: The above results should be considered in the follow-up and treatment planning of invasive ductal carcinoma patients.}, } @article {pmid26613509, year = {2016}, author = {Skazik-Voogt, C and Kühler, K and Ott, H and Czaja, K and Zwadlo-Klarwasser, G and Merk, HF and Amann, PM and Baron, JM}, title = {Myeloid human cell lines lack functional regulation of aryl hydrocarbon receptor-dependent phase I genes.}, journal = {ALTEX}, volume = {33}, number = {1}, pages = {37-46}, doi = {10.14573/altex.1502041}, pmid = {26613509}, issn = {1868-8551}, mesh = {Aryl Hydrocarbon Receptor Nuclear Translocator/*metabolism ; Cell Line ; Cytochrome P-450 CYP1A1/*genetics/metabolism ; Cytochrome P-450 CYP1B1/metabolism ; Dendritic Cells ; Dermatitis, Contact ; *Gene Expression Regulation/drug effects ; Humans ; Langerhans Cells ; Monocytes ; *Myeloid Cells ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; }, abstract = {Primary dendritic cells and myeloid cell lines are used to assess the skin sensitization hazard in in vitro approaches. The aryl hydrocarbon receptor (AhR) modulates expression of CYP enzymes which play a significant role in the bioactivation of various xenobiotics. These studies revealed a strong constitutive expression of the AhR in primary human monocytes, monocyte-derived immature dendritic cells (iDC) and cord blood-derived Langerhans cells (LC). In contrast, mRNA and protein expression of AhR was hardly detectable in the cell lines THP-1 and MUTZ-3. U937 cells and MUTZ-3-derived dendritic (MUTZ-DC) or Langerhans cells (MUTZ-LC) showed about half the expression of AhR compared to iDC. Incubation of cells with the specific AhR-inducer benzo[a]anthracene resulted in an upregulation of CYP and IL-1β mRNA expression in primary monocytes and iDC. CYP1A1 but not CYP1B1 and IL-1β expression was increased by benzo[a]anthracene in these cell lines except for U937 cells. AhR-independent CYP genes were not regulated by benzo[a]anthracene. Constitutive mRNA expression of other non AhR-dependent CYP enzymes was higher in some of the cell lines compared to the corresponding primary cells. This study demonstrates significant differences in expression and regulation of phase I genes in cell lines currently used for in vitro skin sensitization hazard assessment compared to primary cells. Additional studies are required regarding the combination of cutaneous xenobiotic metabolizing enzymes and APC-sensitization for the development of valid in vitro models for skin sensitization assessment.}, } @article {pmid26612847, year = {2016}, author = {Coyne, JD}, title = {Gynecomastia With Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Associated With Invasive Breast Carcinoma in a Male Patient on Antiretroviral Therapy: A Case Report.}, journal = {International journal of surgical pathology}, volume = {24}, number = {2}, pages = {139-141}, doi = {10.1177/1066896915608437}, pmid = {26612847}, issn = {1940-2465}, mesh = {Adult ; Antiretroviral Therapy, Highly Active ; Breast Neoplasms, Male/complications/*pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology ; Gynecomastia/*etiology ; *HIV Infections ; Humans ; Male ; }, abstract = {Breast carcinoma in males is rare although a 4-fold increased incidence is reported in HIV-infected men. Herein we report a case of invasive breast carcinoma in a HIV-positive man on antiretroviral therapy. The carcinoma was associated with features of florid gynecomastia, atypical ductal hyperplasia, ductal carcinoma in situ, and columnar cell change. This combination of morphological changes has not previously been reported in the context of male breast carcinoma and their etiopathological associations are discussed.}, } @article {pmid26610382, year = {2015}, author = {Swain, SM and Nunes, R and Yoshizawa, C and Rothney, M and Sing, AP}, title = {Quantitative Gene Expression by Recurrence Score in ER-Positive Breast Cancer, by Age.}, journal = {Advances in therapy}, volume = {32}, number = {12}, pages = {1222-1236}, pmid = {26610382}, issn = {1865-8652}, mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms/*genetics/mortality/*pathology ; Female ; Gene Expression Profiling ; Humans ; Middle Aged ; Neoplasm Recurrence, Local/*genetics/mortality/*pathology ; Neoplasm Staging ; Receptors, Estrogen/*metabolism ; }, abstract = {INTRODUCTION: Breast cancer in young women (<50 years) has been associated with an increased risk of recurrence and decreased survival compared with patients older than 50. The objective of this analysis was to determine, from a large database of patients with early-stage breast cancer, if the Recurrence Score(®) result (Oncotype DX(®), Genomic Health, Inc, Redwood City, CA, USA) provided clinically meaningful differences in predicted risk of recurrence in younger-compared with older-patients.

METHODS: Tumor samples from patients with estrogen receptor (ER)-positive breast cancers that were successfully processed in the Genomic Health central lab between June 2004 and December 2013 for Recurrence Score and quantitative gene expression of ER, progesterone receptor (PR), and Her/2neu, were included. Descriptive statistics were used to describe the distribution of scores by age group: <40, 40-49, 50-59, 60-69, and ≥70 years, nodal status, and histologic subtype.

RESULTS: Specimens from 394,031 patients [3.3% (n = 13,029) aged <40 years; 15.6% (n = 61,643) aged ≥70 years] were included; 81.6% of patients had invasive ductal carcinoma. Nodal status was specified for 362,001 patients (87.0% negative). Median Recurrence Score results were similar across risk groups. Low (<18)- and high (≥31)- risk Recurrence Score results were seen in 58.5% and 8.5% of patients, respectively. A greater proportion of patients aged <40 (14.1%) than ≥70 (8.8%) years had a high-risk score. ER expression increased as a function of age and PR single-gene and invasion gene group expression were similar across age groups.

CONCLUSION: These data indicate that in patients with ER-positive breast cancer, age alone does not reflect the underlying individual tumor biology, suggesting that the Recurrence Score result may add potentially useful information for personalized treatment decisions.

FUNDING: Genomic Health, Inc.}, } @article {pmid26606518, year = {2015}, author = {Ellinas, C and Allan, N and Durugbo, C and Johansson, A}, title = {How Robust Is Your Project? From Local Failures to Global Catastrophes: A Complex Networks Approach to Project Systemic Risk.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0142469}, pmid = {26606518}, issn = {1932-6203}, mesh = {Algorithms ; *Models, Theoretical ; }, abstract = {Current societal requirements necessitate the effective delivery of complex projects that can do more while using less. Yet, recent large-scale project failures suggest that our ability to successfully deliver them is still at its infancy. Such failures can be seen to arise through various failure mechanisms; this work focuses on one such mechanism. Specifically, it examines the likelihood of a project sustaining a large-scale catastrophe, as triggered by single task failure and delivered via a cascading process. To do so, an analytical model was developed and tested on an empirical dataset by the means of numerical simulation. This paper makes three main contributions. First, it provides a methodology to identify the tasks most capable of impacting a project. In doing so, it is noted that a significant number of tasks induce no cascades, while a handful are capable of triggering surprisingly large ones. Secondly, it illustrates that crude task characteristics cannot aid in identifying them, highlighting the complexity of the underlying process and the utility of this approach. Thirdly, it draws parallels with systems encountered within the natural sciences by noting the emergence of self-organised criticality, commonly found within natural systems. These findings strengthen the need to account for structural intricacies of a project's underlying task precedence structure as they can provide the conditions upon which large-scale catastrophes materialise.}, } @article {pmid26605100, year = {2015}, author = {Mandaliya, H and Baghi, P and Prawira, A and George, MK}, title = {A Rare Case of Paclitaxel and/or Trastuzumab Induced Acute Hepatic Necrosis.}, journal = {Case reports in oncological medicine}, volume = {2015}, number = {}, pages = {825603}, pmid = {26605100}, issn = {2090-6706}, abstract = {Paclitaxel induced mild derangement of liver functions including bilirubin, alkaline phosphatase, and AST has been infrequently noticed in clinical trials. Contrary to Paclitaxel, hepatocellular injury, hepatitis, and liver tenderness are common laboratory and clinical findings with Trastuzumab. However, hepatic failure/necrosis secondary to Paclitaxel or Trastuzumab has never been reported in literature. A 62-year-old lady, previously healthy, was treated with adjuvant therapy for left breast stage II, high grade invasive ductal carcinoma which was node negative, oestrogen receptor negative, progesterone receptor positive, and HER2 receptor positive. After modified radical mastectomy and axillary clearance, she finished four cycles of Doxorubicin/Cyclophosphamide chemotherapy and then commenced on Paclitaxel/Trastuzumab combination chemotherapy. Within twelve hours of first dose of Paclitaxel/Trastuzumab therapy, patient required hospital admission for acute onset respiratory failure. Patient died within 36 hours of therapy and autopsy was suggestive of acute hepatic necrosis without any other significant findings. Detailed investigations were not carried out as event was quick with rapid deterioration. There was no history of prior liver pathology/injury and preliminary investigations for major organ involvement were unremarkable. As per our knowledge, Paclitaxel and/or Trastuzumab induced acute hepatic necrosis has never been reported in literature before, hence difficult to predict.}, } @article {pmid26604502, year = {2015}, author = {Sudha, S and Gopinath, D and Shameena, PM and Dhanalakshmi, J}, title = {Numb chin syndrome associated with metastatic invasive ductal carcinoma of breast.}, journal = {Journal of oral and maxillofacial pathology : JOMFP}, volume = {19}, number = {2}, pages = {239-241}, pmid = {26604502}, issn = {0973-029X}, abstract = {Numb chin syndrome (NCS), also known as mental nerve neuropathy, is characterized by facial and oral numbness restricted to the distribution of the mental nerve. Although not a common neuropathy, the clinical importance of this syndrome is its frequent association with malignancies. A 56-year-old Indian female reported with a complaint of numbness on the left side of chin. She had undergone a radical mastectomy with axillary lymph node dissection for invasive ductal carcinoma of the right breast 4 years ago. Biopsy revealed tumor cells showing pleomorphic hyperchromatic nuclei arranged in cord and nests leading to a diagnosis of metastatic carcinoma of breast origin. Bone scan showed increased uptake in multiple areas in skull, left hemimandible, multiple vertebrae, multiple ribs on either sides, right clavicle both scapulae and sternum, both humeri, multiple pelvic bones and trochanteric region of left femur. The patient was referred to a tertiary cancer institute where she received palliative hormonal and chemotherapy, which helped with her pain and halted the progression of the metastatic disease for past 22 months. The present case depicts the importance of proper recognition of NCS as it may often be the only symptom of an underlying malignancy or the first evidence of dissemination from a primary site as evident in this case.}, } @article {pmid26600624, year = {2015}, author = {Ossa, CA and Herazo, F and Gil, M and Echeverri, C and Ángel, G and Borrero, M and Madrid, J and Jaramillo, R}, title = {Phyllodes tumor of the breast: a clinic-pathologic study of 77 cases in a Hispanic cohort.}, journal = {Colombia medica (Cali, Colombia)}, volume = {46}, number = {3}, pages = {104-108}, pmid = {26600624}, issn = {1657-9534}, mesh = {Adult ; Breast Neoplasms/diagnosis/*pathology/surgery ; Colombia ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Phyllodes Tumor/diagnosis/*pathology/surgery ; Retrospective Studies ; Survival Rate ; }, abstract = {INTRODUCTION: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs).

OBJECTIVE: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center.

METHODS: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used.

RESULTS: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%.

DISCUSSION: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population.}, } @article {pmid26599012, year = {2015}, author = {Mu, QJ and Li, HL and Yao, Y and Liu, SC and Yin, CG and Ma, XZ}, title = {Chromodomain Helicase/ATPase DNA-Binding Protein 1-Like Gene (CHD1L) Expression and Implications for Invasion and Metastasis of Breast Cancer.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0143030}, pmid = {26599012}, issn = {1932-6203}, mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Helicases/antagonists & inhibitors/*biosynthesis/genetics ; DNA-Binding Proteins/antagonists & inhibitors/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Mice ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Proteins/*biosynthesis ; RNA, Small Interfering ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.

METHODS: Immunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.

RESULTS: CHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.

CONCLUSIONS: CHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.}, } @article {pmid26597811, year = {2015}, author = {Lappalainen, AK and Mäki, K and Laitinen-Vapaavuori, O}, title = {Estimate of heritability and genetic trend of intervertebral disc calcification in Dachshunds in Finland.}, journal = {Acta veterinaria Scandinavica}, volume = {57}, number = {}, pages = {78}, pmid = {26597811}, issn = {1751-0147}, mesh = {Animals ; Calcinosis/diagnostic imaging/genetics/prevention & control/*veterinary ; Dog Diseases/diagnostic imaging/*genetics/pathology/prevention & control ; Dogs ; Female ; Finland ; Intervertebral Disc/*pathology ; Intervertebral Disc Degeneration/diagnostic imaging/genetics/prevention & control/*veterinary ; Male ; Mass Screening/*veterinary ; Radiography ; }, abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a hereditary condition particularly common in Dachshunds. The breed is predisposed to early intervertebral disc degeneration and intervertebral disc calcification (IDC). When calcified, these severely degenerated discs are visible in spinal radiographs. Since the number of calcified discs (NCD) is associated with IDD, spinal radiography can be utilized in screening programmes in attempts to diminish the incidence of IDD in Dachshunds. Our aims were to estimate the heritability and genetic trend of NCD in Dachshunds in Finland and to explore the effect of age at the time of radiographic screening. Since the NCD has a highly skewed distribution, a log-transformed NCD (lnNCD) was also used as an analysed trait. The variance components for both traits were estimated, using the restricted maximum likelihood method. The fixed effects of breed variant, sex, as well as year of screening and the random effects of litter and animal were included in the model. The genetic trends in the NCD and lnNCD were assessed from the estimated breeding values (EBVs) of individual dogs by comparing the mean EBV of dogs born in different years. The breeding values were estimated, using the best linear unbiased prediction animal model. The pedigree in the genetic analyses included a total of 9027 dogs, of which 1567 showed results for NCDs.

RESULTS: The heritability estimates of the NCD and lnNCD in Dachshunds were high (0.53 and 0.45, respectively). Small genetic improvements were seen as the mean EBVs increased from 100 to 104 and 105 over a 15-year period. The gain in the entire Dachshund population in Finland may differ from that observed, since less than 10 % of the Dachshunds registered have a screening result for NCD. Age at the time of the screening did not significantly affect the NCD or lnNCD.

CONCLUSIONS: We recommend systematic radiographic screening for IDC in Dachshunds and adopting EBVs as a tool for selecting breeding dogs. Age at the time of the radiographic screening may not be as important as previously suggested.}, } @article {pmid26597806, year = {2016}, author = {El-Gendi, SM and Mostafa, MF}, title = {Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma.}, journal = {Pathology oncology research : POR}, volume = {22}, number = {3}, pages = {461-470}, pmid = {26597806}, issn = {1532-2807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Core Binding Factor Alpha 1 Subunit/*metabolism ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Middle Aged ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {The Runx family of transcription factors has been implicated in cancer progression, both positively and negatively. Recent studies assigned a role for Runx2 in promoting breast cancer metastasis. However, the role of Runx2 during the early stage of breast carcinoma and its association with clinical outcomes remain unknown. Assessing the clinicopathological significance of Runx2 expression in a cohort of breast invasive ductal carcinomas (IDC). The correlation of nuclear Runx2 LI with clinicopathological parameters was assessed in 84 IDCs. To study the association of Runx2 with patient outcomes, in addition to treating it as a continuous variable, Runx2 was categorized by its median value (65) and by an additional two cut-off points determined by ROC curve analyses, at 45 for disease free survival (DFS) and 40 for overall survival (OS). Multivariate Cox regression models were also constructed. We used the best subset regression to identify models that predict DFS and OS with as few predictors as possible, and validation was performed. Based on the "Predicted R(2)", the three best models were identified. Using Cox-regression, the interaction between Runx2 and other clinicopathological terms was tested. Runx2 LI was significantly associated only with positive Her-2 status, and did not correlate significantly with other clinicopathological parameters. Although Runx2 LI, in the continuous form and when categorized by the median, did not correlate significantly with DFS and OS; after it was categorized using the optimal cut-off points determined using ROC curve analysis, the patients with Runx2 LI >45 % showed a significantly higher event rate and shorter DFS (P = 0.047), whereas patients with Runx2 LI >40 % showed a significantly shorter OS (P = 0.050). Moreover, Runx2 LI contributed significantly in the models built to predict DFS and OS. For DFS, no interaction terms contributed significantly to the models. However, among stage IV cases, the interaction term between centred Runx2 and ER significantly contributed to the prediction of OS. Runx2 was a significant predictor of OS in this model. Runx2 has a role in biological behaviour and affects the outcome of IDC; therefore, its inhibition may be a new therapeutic strategy. The predictability of Runx2 for OS in stage IV tumours differs with different ER states. The pattern of this difference was not determined because the sample size was not sufficient to allow pattern testing.}, } @article {pmid26595663, year = {2016}, author = {Dadashi, F and Millet, GP and Aminian, K}, title = {Front-crawl stroke descriptors variability assessment for skill characterisation.}, journal = {Journal of sports sciences}, volume = {34}, number = {15}, pages = {1405-1412}, doi = {10.1080/02640414.2015.1114134}, pmid = {26595663}, issn = {1466-447X}, mesh = {Accelerometry/methods ; Adaptation, Physiological ; Adolescent ; Arm/*physiology ; Biomechanical Phenomena ; Female ; Humans ; Male ; Motor Skills/*physiology ; Physical Conditioning, Human ; Swimming/*physiology ; Time and Motion Studies ; Young Adult ; }, abstract = {The goal of this article is to characterise front-crawl swimming skill based on variability pattern of technique descriptors. Nine national level and nine recreational swimmers performed three 300 m trials in a 50 m outdoor pool, at 70%, 80% and 90% of their front-crawl 400 m personal best time. Using wearable inertial measurement units (IMUs) and validated algorithms we assessed the variability of technique descriptors at each arm cycle (139 ± 17 per trial). We calculated the duration of pull, push and non-propulsive phases, index of coordination (IdC), stroke length, stroke rate and intra-cyclic velocity variation. To track intra-trial technique variability, we calculated the Cauchy index to quantify the stability of multidimensional technique descriptors in space-time. Skilled swimmers, having access to divers motor solutions, achieved significantly higher velocities at similar intensities and similar IdC (P < 0.01) with more stable motor pattern (smaller Cauchy index). Besides, the similarity of intra-cyclic velocity variation at different intensities denotes that skilled swimmers used a wider dynamic range of velocity. We also introduced cycle velocity variation as a new metric of propulsive pattern repeatability and showed cycle velocity variation changes is correlated to the Cauchy index (rx,y = 0.72, P < 0.01). These findings indicate that IdC can be used as a predictor of performance only when swimmers of homogeneous expertise level are studied and suggest the scrutiny of both intra-cyclic velocity variation and cycle velocity variation as a requisite to study the motor adaptations of the swimmer in facing new constraints.}, } @article {pmid26589316, year = {2015}, author = {Jeffries, DO and Neal, CH and Noroozian, M and Joe, AI and Pinsky, RW and Goodsitt, MM and Helvie, MA}, title = {Surgical biopsy is still necessary for BI-RADS 4 calcifications found on digital mammography that are technically too faint for stereotactic core biopsy.}, journal = {Breast cancer research and treatment}, volume = {154}, number = {3}, pages = {557-561}, doi = {10.1007/s10549-015-3640-8}, pmid = {26589316}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Calcinosis/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology/surgery ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Stereotaxic Techniques ; }, abstract = {The purpose of this study was to evaluate the outcome of faint BI-RADS 4 calcifications detected with digital mammography that were not amenable to stereotactic core biopsy due to suboptimal visualization. Following Institutional Review Board approval, a HIPAA compliant retrospective search identified 665 wire-localized surgical excisions of calcifications in 606 patients between 2007 and 2010. We included all patients that had surgical excision for initial diagnostic biopsy due to poor calcification visualization, whose current imaging was entirely digital and performed at our institution and who did not have a diagnosis of breast cancer within the prior 2 years. The final study population consisted of 20 wire-localized surgical biopsies in 19 patients performed instead of stereotactic core biopsy due to poor visibility of faint calcifications. Of the 20 biopsies, 4 (20% confidence intervals 2, 38%) were malignant, 5 (25%) showed atypia and 11 (55%) were benign. Of the malignant cases, two were invasive ductal carcinoma (2 and 1.5 mm), one was intermediate grade DCIS and one was low-grade DCIS. Malignant calcifications ranged from 3 to 12 mm. The breast density was scattered in 6/19 (32%), heterogeneously dense in 11/19 (58%) and extremely dense in 2/19 (10%). Digital mammography-detected faint calcifications that were not amenable to stereotactic biopsy due to suboptimal visualization had a risk of malignancy of 20%. While infrequent, these calcifications should continue to be considered suspicious and surgical biopsy recommended.}, } @article {pmid26588055, year = {2016}, author = {Tan, X and Fu, Y and Chen, L and Lee, W and Lai, Y and Rezaei, K and Tabbara, S and Latham, P and Teal, CB and Man, YG and Siegel, RS and Brem, RF and Fu, SW}, title = {miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.}, journal = {Oncotarget}, volume = {7}, number = {1}, pages = {293-307}, pmid = {26588055}, issn = {1949-2553}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/pharmacology ; Blotting, Western ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Cycle/drug effects/genetics ; Cell Line, Tumor ; Cell Survival/drug effects/genetics ; Cisplatin/pharmacology ; *Down-Regulation ; Epirubicin/pharmacology ; Epithelial-Mesenchymal Transition/*genetics ; Fluorouracil/pharmacology ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*genetics/metabolism ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs/*genetics ; Microscopy, Confocal ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.}, } @article {pmid26581728, year = {2015}, author = {Ayal, S and Gino, F and Barkan, R and Ariely, D}, title = {Three Principles to REVISE People's Unethical Behavior.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {10}, number = {6}, pages = {738-741}, doi = {10.1177/1745691615598512}, pmid = {26581728}, issn = {1745-6924}, mesh = {Humans ; *Morals ; Motivation ; *Public Policy ; Self Concept ; *Social Behavior ; *Social Control, Informal ; United States ; }, abstract = {Dishonesty and unethical behavior are widespread in the public and private sectors and cause immense annual losses. For instance, estimates of U.S. annual losses indicate $1 trillion paid in bribes, $270 billion lost due to unreported income, and $42 billion lost in retail due to shoplifting and employee theft. In this article, we draw on insights from the growing fields of moral psychology and behavioral ethics to present a three-principle framework we call REVISE. This framework classifies forces that affect dishonesty into three main categories and then redirects those forces to encourage moral behavior. The first principle, reminding, emphasizes the effectiveness of subtle cues that increase the salience of morality and decrease people's ability to justify dishonesty. The second principle, visibility, aims to restrict anonymity, prompt peer monitoring, and elicit responsible norms. The third principle, self-engagement, increases people's motivation to maintain a positive self-perception as a moral person and helps bridge the gap between moral values and actual behavior. The REVISE framework can guide the design of policy interventions to defeat dishonesty.}, } @article {pmid26579563, year = {2016}, author = {Bedair, R and Graves, MJ and Patterson, AJ and McLean, MA and Manavaki, R and Wallace, T and Reid, S and Mendichovszky, I and Griffiths, J and Gilbert, FJ}, title = {Effect of Radiofrequency Transmit Field Correction on Quantitative Dynamic Contrast-enhanced MR Imaging of the Breast at 3.0 T.}, journal = {Radiology}, volume = {279}, number = {2}, pages = {368-377}, doi = {10.1148/radiol.2015150920}, pmid = {26579563}, issn = {1527-1315}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Contrast Media/pharmacokinetics ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Signal-To-Noise Ratio ; }, abstract = {PURPOSE: To investigate the effects of radiofrequency transmit field (B1(+)) correction on (a) the measured T1 relaxation times of normal breast tissue and malignant lesions and (b) the pharmacokinetically derived parameters of malignant breast lesions at 3 T.

MATERIALS AND METHODS: Ethics approval and informed consent were obtained. Between May 2013 and January 2014, 30 women (median age, 58 years; range, 32-83 years) with invasive ductal carcinoma of at least 10 mm were recruited to undergo dynamic contrast material-enhanced magnetic resonance (MR) imaging before surgery. B1(+) and T1 mapping sequences were performed to determine the effect of B1(+) correction on the native tissue relaxation time (T10) of fat, parenchyma, and malignant lesions in both breasts. Pharmacokinetic parameters were calculated before and after correction for B1(+) variations. Results were correlated with histologic grade by using the Kruskal-Wallis test.

RESULTS: Measurements showed a mean 37% flip angle difference between the right and left breast, which resulted in a 61% T10 difference in fat and a 41.5% difference in parenchyma between the two breasts. The T1 of lesions in the right breast increased by 58%, whereas that of lesions in the left breast decreased by 30% after B1(+) correction. The whole-tumor transendothelial permeability across the vascular compartment(K(trans)) of lesions in the right breast decreased by 41%, and that of lesions in the left breast increased by 46% after correction. A systematic increase in K(trans) was observed, with significant differences found across the histologic grades (P < .001). The effect size of B1(+) correction on K(trans) calculation was large for lesions in the right breast and moderate for lesions in the left breast (Cohen effect size, d = 0.86 and d = 0.59, respectively).

CONCLUSION: B1(+) correction demonstrates a substantial effect on the results of quantitative dynamic contrast-enhanced analysis of breast tissue at 3 T, which propagates into the pharmacokinetic analysis of tumors that is dependent on whether the tumor is located in the right or left breast.}, } @article {pmid26576347, year = {2015}, author = {Ataei-Kachouei, M and Nadaf, J and Akbari, MT and Atri, M and Majewski, J and Riazalhosseini, Y and Garshasbi, M}, title = {Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.}, journal = {Iranian journal of public health}, volume = {44}, number = {10}, pages = {1348-1352}, pmid = {26576347}, issn = {2251-6085}, abstract = {BACKGROUND: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.

METHODS: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.

RESULTS: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to heterozygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.

CONCLUSION: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.}, } @article {pmid26572989, year = {2015}, author = {Papadimitriou, M and Kaptanis, S and Polymeropoulos, E and Mitsopoulos, G and Stogiannis, D and Caroni, C and Vaiopoulos, G and Panayiotides, JG and Karakitsos, P}, title = {Nuclear grade plus proliferation grading system for invasive ductal carcinoma of the breast: validation in a tertiary referral hospital cohort.}, journal = {American journal of clinical pathology}, volume = {144}, number = {6}, pages = {837-843}, doi = {10.1309/AJCPVH6FED2ZATUP}, pmid = {26572989}, issn = {1943-7722}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Proliferation ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading/*methods ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Tertiary Care Centers ; }, abstract = {OBJECTIVES: For patients with invasive breast cancer, management decisions are informed by tumor grade according to the Nottingham Grading System (NGS), either on its own or as part of the Nottingham Prognostic Index (NPI). A system retaining the nuclear grade element but substituting the two subjective components, mitosis count and tubule formation, of the NGS with a proliferation index based on Ki-67 (MIB-1) has been proposed (nuclear grade plus proliferation [N+P] grading).

METHODS: We validated the prognostic value of this grading system on a population of 322 women.

RESULTS: N+P grading resulted in more grade I tumors (47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and grade III (20.1% vs 44%) tumors compared with NGS. The NPI calculated based on N+P grade had a similar association with survival (P < .001; odds ratio, 1.729) as the NPI calculated on the basis of the NGS grade (P < .001; odds ratio, 1.668).

CONCLUSIONS: The N+P system seems equivalent to the NGS system.}, } @article {pmid26572142, year = {2016}, author = {Ben-David, BM and van Lieshout, PH and Shakuf, V}, title = {Sensory source for stroop effects in persons after TBI: support from fNIRS-based investigation.}, journal = {Brain imaging and behavior}, volume = {10}, number = {4}, pages = {1135-1136}, doi = {10.1007/s11682-015-9477-2}, pmid = {26572142}, issn = {1931-7565}, mesh = {*Brain Injuries, Traumatic ; Humans ; *Oxyhemoglobins ; Spectroscopy, Near-Infrared ; *Stroop Test ; }, } @article {pmid26571053, year = {2016}, author = {Derby, DS and Peleg-Sagy, T and Doron, G}, title = {Schema Therapy in Sex Therapy: A Theoretical Conceptualization.}, journal = {Journal of sex & marital therapy}, volume = {42}, number = {7}, pages = {648-658}, doi = {10.1080/0092623X.2015.1113586}, pmid = {26571053}, issn = {1521-0715}, mesh = {Biomedical Research/standards ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; Male ; Models, Psychological ; Personality Disorders/*therapy ; Psychotherapy, Brief ; Sexual Dysfunctions, Psychological/*therapy ; }, abstract = {Schema therapy is an integrative approach of psychotherapy developed by Jeffrey E. Young. Its aim is to help clients explore and understand their deep emotional needs and meet them in a healthy manner. It is suitable for complex pathologies, such as comorbidities and personality disorders. In sex therapy, schema therapy can serve as a method for a deep, evidence-based, integrative conceptualization of a client's difficulties and needs. However, its principles have never been demonstrated in sex therapy. In this paper, we briefly review schema therapy and introduce schema domains. We bring a case study of a couple undergoing sex therapy from the cognitive-behavioral perspective. We then return to the same case study, in order to demonstrate the usefulness of a schema therapy conceptualization.}, } @article {pmid26568439, year = {2016}, author = {Tang, R and Saksena, M and Coopey, SB and Fernandez, L and Buckley, JM and Lei, L and Aftreth, O and Koerner, F and Michaelson, J and Rafferty, E and Brachtel, E and Smith, BL}, title = {Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens.}, journal = {The British journal of radiology}, volume = {89}, number = {1058}, pages = {20150581}, pmid = {26568439}, issn = {1748-880X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Female ; Humans ; Imaging, Three-Dimensional ; Mammography ; Mastectomy, Segmental ; Middle Aged ; Multimodal Imaging ; Neoplasm Invasiveness/*diagnostic imaging/pathology ; Radiographic Image Interpretation, Computer-Assisted/methods ; X-Ray Microtomography/*methods ; }, abstract = {OBJECTIVES: Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging.

METHODS: A tabletop micro-CT was used to image breast lumpectomy specimens. The largest tumour dimension on three-dimensional reconstructed micro-CT images of the specimen was compared with the measurements determined by pre-operative mammography, ultrasound and MRI. The largest dimension of pathologic invasive cancer size was used as the gold standard reference to assess the accuracy of imaging assessments.

RESULTS: 50 invasive breast cancer specimens in 50 patients had micro-CT imaging. 42 were invasive ductal carcinoma, 6 were invasive lobular carcinoma and 2 were other invasive cancer. Median patient age was 63 years (range 33-82 years). When compared with the largest pathologic tumour dimension, micro-CT measurements had the best correlation coefficient (r = 0.82, p < 0.001) followed by MRI (r = 0.78, p < 0.001), ultrasound (r = 0.61, p < 0.001) and mammography (r = 0.40, p < 0.01). When compared with pre-operative modalities, micro-CT had the best correlation coefficient (r = 0.86, p < 0.001) with MRI, followed by ultrasound (r = 0.60, p < 0.001) and mammography (r = 0.54, p < 0.001). Overall, mammography and ultrasound tended to underestimate the largest tumour dimension, while MRI and micro-CT overestimated the largest tumour dimension more frequently.

CONCLUSION: Micro-CT is a potentially useful tool for accurate assessment of tumour dimensions within a lumpectomy specimen. Future studies need to be carried out to see if this technology could have a role in margin assessment.

ADVANCES IN KNOWLEDGE: Micro-CT is a promising new technique which could potentially be used for rapid assessment of breast cancer dimensions in an intact lumpectomy specimen in order to guide surgical excision.}, } @article {pmid26566041, year = {2015}, author = {Li, CZ and Li, CC and Lin, MC and Chih-Chuan, H and Chen, NF and Chen, CL and Tang, CT}, title = {A Clinical Pitfall: Optimal Management of Single Dural-based Metastatic Carcinoma of the Breast Mimicking Meningioma.}, journal = {The neurologist}, volume = {20}, number = {5}, pages = {93-95}, doi = {10.1097/NRL.0000000000000059}, pmid = {26566041}, issn = {2331-2637}, mesh = {Brain Neoplasms/diagnosis/*secondary/therapy ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Female ; Fluorodeoxyglucose F18/metabolism ; Humans ; Magnetic Resonance Imaging ; Meningeal Neoplasms/*physiopathology ; Meningioma/*physiopathology ; Middle Aged ; Positron-Emission Tomography ; }, abstract = {Meningioma is the most common benign brain lesion in adults. Conservative treatment is suggested if there is no obvious neurological symptom or mass effect, but cerebral metastases require aggressive therapy. Single dural-based metastatic carcinoma mimicking meningioma is uncommon. Here is a case of clinical dilemma between meningioma and metastatic carcinoma mimicking meningioma. A woman with a history of invasive ductal carcinoma of the breast presented with headache and blurred vision. Brain computed tomography and magnetic resonance imaging (MRI) both gave the impression of meningioma. After surgical resection of the brain lesion, histopathology revealed that it was a metastatic lesion from the breast. This report discussed the optimal management of single dural-based metastatic carcinoma mimicking meningioma.}, } @article {pmid26564123, year = {2016}, author = {Moccia, M and Erro, R and Picillo, M and Santangelo, G and Spina, E and Allocca, R and Longo, K and Amboni, M and Palladino, R and Assante, R and Pappatà, S and Pellecchia, MT and Barone, P and Vitale, C}, title = {A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.}, journal = {Sleep}, volume = {39}, number = {2}, pages = {405-412}, pmid = {26564123}, issn = {1550-9109}, mesh = {Adult ; Age of Onset ; Aged ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Incidence ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/*complications/diagnosis/drug therapy/*epidemiology ; Prevalence ; Random Allocation ; Restless Legs Syndrome/*complications/diagnosis/*epidemiology/physiopathology ; Sleep Wake Disorders/complications ; Surveys and Questionnaires ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.

METHODS: One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.

RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).

CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.}, } @article {pmid26563847, year = {2016}, author = {Siciliano, M and Raimo, S and Tufano, D and Basile, G and Grossi, D and Santangelo, F and Trojano, L and Santangelo, G}, title = {The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {37}, number = {3}, pages = {385-392}, pmid = {26563847}, issn = {1590-3478}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Attention ; Cognition ; Cognition Disorders/diagnosis ; Educational Status ; Female ; Humans ; Italy ; Language ; Male ; Memory ; Mental Status Schedule ; Middle Aged ; *Neuropsychological Tests/statistics & numerical data ; Orientation ; Reference Values ; Sex Factors ; Space Perception ; Young Adult ; }, abstract = {The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.}, } @article {pmid26557763, year = {2015}, author = {Badowska-Kozakiewicz, AM and Patera, J and Sobol, M and Przybylski, J}, title = {The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women.}, journal = {Contemporary oncology (Poznan, Poland)}, volume = {19}, number = {3}, pages = {220-225}, pmid = {26557763}, issn = {1428-2526}, abstract = {AIM OF THE STUDY: Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status.

MATERIAL AND METHODS: Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies.

RESULTS: Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (-) tumours.

CONCLUSIONS: Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics.}, } @article {pmid26552553, year = {2015}, author = {Sánchez-Borque, P and Rubio, JM and Benezet-Mazuecos, J and Quiñones, MA and Farré, J}, title = {Atrial fibrillation with Wolff-Parkinson-White syndrome in epilepsy: A potentially fatal combination.}, journal = {Seizure}, volume = {32}, number = {}, pages = {1-3}, doi = {10.1016/j.seizure.2015.08.002}, pmid = {26552553}, issn = {1532-2688}, mesh = {Adult ; Atrial Fibrillation/*complications/physiopathology ; Electrocardiography/methods ; Epilepsy/*complications/physiopathology ; Female ; Humans ; Seizures/complications/physiopathology ; Video Recording/methods ; Wolff-Parkinson-White Syndrome/*complications/physiopathology ; }, } @article {pmid26551252, year = {2016}, author = {Shoshani, A and Nakash, O and Zubida, H and Harper, RA}, title = {School engagement, acculturation, and mental health among migrant adolescents in Israel.}, journal = {School psychology quarterly : the official journal of the Division of School Psychology, American Psychological Association}, volume = {31}, number = {2}, pages = {181-197}, doi = {10.1037/spq0000133}, pmid = {26551252}, issn = {1939-1560}, mesh = {*Acculturation ; Adolescent ; Aptitude ; Female ; Humans ; Interpersonal Relations ; Israel/ethnology ; Jews/psychology ; Male ; Mental Disorders/ethnology ; *Mental Health ; Resilience, Psychological ; Risk-Taking ; Schools ; Social Adjustment ; Socioeconomic Factors ; Students ; Transients and Migrants/*psychology ; }, abstract = {This study aimed to explore the role of school engagement and the mediation effect of acculturation in predicting 1.5 and second-generation migrant adolescents' mental health and risk behaviors. Participants included 448 seventh to tenth grade Israeli students (mean age 14.50, 53% boys): 128 non-Jewish 1.5 generation migrant adolescents (children of migrants living in Israel), 118 second-generation migrants (children of migrants born and living in Israel), and an age-matched sample of 202 native-born Jewish adolescents. All participants completed a battery of questionnaires assessing mental health symptoms, engagement in risk behaviors, social adjustment, and school engagement. Both migrant adolescent groups also completed an acculturation questionnaire. Differences between groups in school engagement, mental health symptoms, and risk behavior were examined, and structural equation modeling (SEM) was used to investigate the hypothesized mediating effect of acculturation. Findings revealed substantially higher levels of mental health symptoms (p < .001) and risk behaviors (p = .001) among 1.5 and second-generation migrant adolescents compared with native-born adolescents, with no significant differences between 1.5 generation and second-generation migrants. Migrants' age and gender were associated with mental health symptoms and risk behaviors-older participants engaged in more risk behaviors (p = .02), and females had elevated mental health symptoms (p = .007). Identification with the host country mediated the relationships between school engagement and mental health symptoms (ps .006 and .008) and risk behaviors (ps .001 and .004) in 1.5 generation and second-generation migrants, respectively. The results are discussed in reference to current theories and research, as well as practical implications for prevention and intervention. (PsycINFO Database Record}, } @article {pmid26546077, year = {2016}, author = {Azagra, R and Zwart, M and Aguyé, A and Martín-Sánchez, JC and Casado, E and Díaz-Herrera, MA and Moriña, D and Cooper, C and Díez-Pérez, A and Dennison, EM and , }, title = {Fracture experience among participants from the FROCAT study: what thresholding is appropriate using the FRAX tool?.}, journal = {Maturitas}, volume = {83}, number = {}, pages = {65-71}, doi = {10.1016/j.maturitas.2015.10.002}, pmid = {26546077}, issn = {1873-4111}, support = {19583/ARC_/Arthritis Research UK/United Kingdom ; MC_U147585827/MRC_/Medical Research Council/United Kingdom ; MC_U147585819/MRC_/Medical Research Council/United Kingdom ; MC_UP_A620_1014/MRC_/Medical Research Council/United Kingdom ; 19583/VAC_/Versus Arthritis/United Kingdom ; MC_UU_12011/1/MRC_/Medical Research Council/United Kingdom ; G0400491/MRC_/Medical Research Council/United Kingdom ; MC_U147585824/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; *Algorithms ; Female ; Humans ; Middle Aged ; Osteoporotic Fractures/*epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Spain/epidemiology ; }, abstract = {OBJECTIVE: To perform an external validation of FRAX algorithm thresholds for reporting level of risk of fracture in Spanish women (low < 5%; intermediate ≥ 5% and < 7.5%; high ≥ 7.5%) taken from a prospective cohort "FRIDEX".

METHODS: A retrospective study of 1090 women aged ≥ 40 and ≤ 90 years old obtained from the general population (FROCAT cohort). FRAX was calculated with data registered in 2002. All fractures were validated in 2012. Sensitivity analysis was performed.

RESULTS: When analyzing the cohort (884) excluding current or past anti osteoporotic medication (AOM), using our nominated thresholds, among the 621 (70.2%) women at low risk of fracture, 5.2% [CI95%: 3.4-7.6] sustained a fragility fracture; among the 99 at intermediate risk, 12.1% [6.4-20.2]; and among the 164 defined as high risk, 15.9% [10.6-24.2]. Sensitivity analysis against model risk stratification FRIDEX of FRAX Spain shows no significant difference. By including 206 women with AOM, the sensitivity analysis shows no difference in the group of intermediate and high risk and minimal differences in the low risk group.

CONCLUSIONS: Our findings support and validate the use of FRIDEX thresholds of FRAX when discussing the risk of fracture and the initiation of therapy with patients.}, } @article {pmid26543228, year = {2016}, author = {Hart, PC and Ratti, BA and Mao, M and Ansenberger-Fricano, K and Shajahan-Haq, AN and Tyner, AL and Minshall, RD and Bonini, MG}, title = {Caveolin-1 regulates cancer cell metabolism via scavenging Nrf2 and suppressing MnSOD-driven glycolysis.}, journal = {Oncotarget}, volume = {7}, number = {1}, pages = {308-322}, pmid = {26543228}, issn = {1949-2553}, support = {R01 DK044525/DK/NIDDK NIH HHS/United States ; R01 HL071626/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Caveolin 1/*genetics/metabolism ; Cell Line ; *Glycolysis ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Kelch-Like ECH-Associated Protein 1 ; MCF-7 Cells ; Mammary Neoplasms, Animal/genetics/metabolism ; Mice ; Microscopy, Confocal ; NF-E2-Related Factor 2/genetics/*metabolism ; Prognosis ; Protein Binding ; RNA Interference ; Superoxide Dismutase/genetics/*metabolism ; Survival Analysis ; }, abstract = {Aerobic glycolysis is an indispensable component of aggressive cancer cell metabolism. It also distinguishes cancer cells from most healthy cell types in the body. Particularly for this reason, targeting the metabolism to improve treatment outcomes has long been perceived as a potentially valuable strategy. In practice, however, our limited knowledge of why and how metabolic reprogramming occurs has prevented progress towards therapeutic interventions that exploit the metabolic peculiarities of tumors. We recently described that in breast cancer, MnSOD upregulation is both necessary and sufficient to activate glycolysis. Here, we focused on determining the molecular mechanisms of MnSOD upregulation. We found that Caveolin-1 (Cav-1) is a central component of this mechanism due to its suppressive effects of NF-E2-related factor 2 (Nrf2), a transcription factor upstream of MnSOD. In transformed MCF10A(Er/Src) cells, Cav-1 loss preceded the activation of Nrf2 and its induction of MnSOD expression. Consistently, with previous observations, MnSOD expression secondary to Nrf2 activation led to an increase in the glycolytic rate dependent on mtH2O2 production and the activation of AMPK. Moreover, rescue of Cav-1 expression in a breast cancer cell line (MCF7) suppressed Nrf2 and reduced MnSOD expression. Experimental data were reinforced by epidemiologic nested case-control studies showing that Cav-1 and MnSOD are inversely expressed in cases of invasive ductal carcinoma, with low Cav-1 and high MnSOD expression being associated with lower 5-year survival rates and molecular subtypes with poorest prognosis.}, } @article {pmid26520652, year = {2015}, author = {Ishii, M and Kimura, Y and Sugita, S and Imamura, M and Ito, T and Nobuoka, T and Meguro, M and Hasegawa, T and Mizuguchi, T and Hirata, K}, title = {Surgical and oncological impact of main pancreatic duct spread in invasive ductal adenocarcinoma: A clinicopathological study of 184 resected cases.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {15}, number = {6}, pages = {681-687}, doi = {10.1016/j.pan.2015.09.017}, pmid = {26520652}, issn = {1424-3911}, mesh = {Adenocarcinoma/pathology/*surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Retrospective Studies ; }, abstract = {BACKGROUND/OBJECTIVES: This study examined main pancreatic ductal spread in invasive ductal adenocarcinoma (IDC) of the pancreas.

METHODS: Data from IDC patients who underwent radical surgery from 1990 to 2013 in our hospital were examined retrospectively. Incidence of intraductal spread of pancreatic cancer (IS), distance from the tumor edge, direction of IS and clinicopathological factors associated with the presence of IS were retrospectively examined with data from IDC patients who underwent radical surgery.

RESULTS: Among 260 IDC patients who underwent surgery, 184 eligible cases, IS was identified in 42 patients (22.8%) and mean length of IS was 18.7 ± 21.6 mm. Mean distances on the ampullary and distal sides of IS were 11.1 mm and 11.6 mm. IS was significantly more frequent in localized tumors (UICC T1-2 vs. 3-4, p = 0.007), with tumor diameter ≤2 cm (p = 0.034) and in cases with scarce microscopic perineural invasion (p = 0.047). Among patients who underwent pancreaticoduodenectomy and distal pancreatectomy, IS presence (11.6 vs. 21.8%), mean distance to the contralateral side (11.4 vs. 11.6 mm), and IS ≥ 2 cm (3.3 vs. 4.7%) showed no significant differences. Overall survival did not differ significantly between IS-positive and -negative patients in the full analysis set or propensity score-matched patients (42 matched pairs).

CONCLUSIONS: In setting resectional margins at 2 cm, a small proportion of cases (3.8%) showed positive surgical margins. Localized tumor (UICC: T1-2, or <2 cm in diameter) requires more care with surgical margins, warranting intraoperative frozen sections.}, } @article {pmid26516324, year = {2015}, author = {Eslamifar, A and Ramezani, A and Azadmanesh, K and Bidari-Zerehpoosh, F and Banifazl, M and Aghakhani, A}, title = {Assessment of the Association between Human Papillomavirus Infection and Breast Carcinoma.}, journal = {Iranian journal of pathology}, volume = {10}, number = {1}, pages = {41-46}, pmid = {26516324}, issn = {1735-5303}, abstract = {BACKGROUND AND OBJECTIVES: Breast cancer is the most common malignancy in women throughout the world. There are controversial reports on the role of human papillomavirus (HPV) infection in breast carcinogenesis. The aim of this study was to assess the presence of HPV-DNA in invasive breast carcinoma to determine the association between HPV infection and breast carcinoma.

METHODS: The study included formalin-fixed paraffin-embedded tissue samples of 100 cases with invasive ductal carcinoma of breast and 50 control tissues of mammoplasty specimens. HPV-DNA was purified and amplified through GP5+/GP6+ and MY09/MY11 primers.

RESULTS: All tested carcinomas as well as normal tissues were negative for all types of HPV in PCR assay.

CONCLUSION: Our results do not support the association between HPV infection and breast carcinoma. Further studies involving larger number of cases are required to elucidate the role of HPV infection in breast carcinogenesis.}, } @article {pmid26511818, year = {2016}, author = {Chang, JS and Lee, J and Kim, HJ and Kim, KH and Yun, M and Kim, SI and Keum, KC and Suh, CO and Kim, YB}, title = {(18)F-FDG/PET May Help to Identify a Subgroup of Patients with T1-T2 Breast Cancer and 1-3 Positive Lymph Nodes Who Are at a High Risk of Recurrence after Mastectomy.}, journal = {Cancer research and treatment}, volume = {48}, number = {2}, pages = {508-517}, pmid = {26511818}, issn = {2005-9256}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology/radiotherapy ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*diagnostic imaging/*pathology/radiotherapy ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; *Positron-Emission Tomography ; Risk Assessment ; Risk Factors ; Tumor Burden ; }, abstract = {PURPOSE: The purpose of this study is to assess the utility of positron emission tomography (PET) for predicting recurrence among patients with T1-T2/N1 breast cancer who were treated with mastectomy.

MATERIALS AND METHODS: Of 712 consecutive patients with T1-T2/N1 breast cancer treated during 2003-2012, 109 had undergone preoperative (18)F-fluorodeoxyglucose/PET and were included. Metabolic (maximum standardized uptake value [SUVmax]), volumetric (metabolic tumor volume [MTV]), and combined (total lesion glycolysis [TLG]) indices were measured. The resulting values were analyzed and compared with clinical outcome.

RESULTS: At the median follow-up of 46.7 months, the 3-year relapse-free survival (RFS) rate was 95.2%. SUVmax (area under curve, 0.824) was more useful than MTV or TLG as a means of identifying patients at high risk for any recurrence. In multivariate analysis, SUVmax remained an independent risk factor for RFS (p=0.006). Using the method of Contal and O'Quigley, a SUVmax threshold of 5.36 showed the best predictive performance. The PET-based high-risk group (≥ 5.36 in either breast or nodes) had more T1c-T2, high-grade, hormone-receptor negative, and invasive ductal carcinoma tumors than the low-risk group (< 5.36 in both breast and nodes). The prognosis was much worse when high SUVmax (≥ 5.36) was detected in nodes (p < 0.001). In the no-radiotherapy cohort, the PET-based high-risk group had increased risk of locoregional recurrence when compared to the low-risk group (p=0.037).

CONCLUSION: High SUVmax on preoperative PET showed association with elevated risk of locoregional recurrence and any recurrence. Pre-treatment PET may improve assessments of recurrence risk and clarify indications for post-mastectomy radiotherapy in this subset of patients.}, } @article {pmid26511489, year = {2015}, author = {Atwell, LL and Zhang, Z and Mori, M and Farris, P and Vetto, JT and Naik, AM and Oh, KY and Thuillier, P and Ho, E and Shannon, J}, title = {Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {8}, number = {12}, pages = {1184-1191}, pmid = {26511489}, issn = {1940-6215}, support = {P01 CA090890/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; R21 CA132236/CA/NCI NIH HHS/United States ; R21 CA132236-01A2/CA/NCI NIH HHS/United States ; P30 CA069533/CA/NCI NIH HHS/United States ; P30 ES000210/ES/NIEHS NIH HHS/United States ; }, mesh = {Anticarcinogenic Agents/pharmacokinetics/*therapeutic use ; Biological Availability ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*prevention & control ; Chemoprevention/methods ; Dietary Supplements ; Double-Blind Method ; Female ; Humans ; Immunohistochemistry ; Isothiocyanates/pharmacokinetics/*therapeutic use ; Mass Spectrometry ; Sulfoxides ; }, abstract = {Epidemiologic studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2- to 8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ, or invasive ductal carcinoma breast tissues. Within the supplement group, Ki-67 (P = 0.003) and HDAC3 (P = 0.044) levels significantly decreased in benign tissue. Pre-to-postintervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (P = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.}, } @article {pmid26511082, year = {2016}, author = {Ferré, R and Ianculescu, V and Ciolovan, L and Mathieu, MC and Uzan, C and Canale, S and Delaloge, S and Dromain, C and Balleyguier, C}, title = {Diagnostic Performance of MR-guided Vacuum-Assisted Breast Biopsy: 8 Years of Experience.}, journal = {The breast journal}, volume = {22}, number = {1}, pages = {83-89}, doi = {10.1111/tbj.12519}, pmid = {26511082}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Image-Guided Biopsy/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; Vacuum ; Young Adult ; }, abstract = {Breast magnetic resonance imaging (MRI) has demonstrated increased sensitivity over conventional imaging in identifying and characterizing in situ and invasive, multifocal, and multicentric disease. A histologic diagnosis is required for any enhancing lesion displaying suspicious features, especially in the presence of lower and often variable reported specificity values. Breast MRI findings occult on mammography and ultrasound should undergo an MR-guided biopsy. We retrospectively evaluate our 8 years' experience with this procedure. Our study included 259 lesions in 255 consecutive patients referred for MR-guided breast biopsy. MRI screening of women at a high risk for developing breast cancer accounted for 84 lesions, 54 lesions were detected on MRI staging for multifocal and multicentric disease, and 115 were incidental findings or lesions that presented diagnosis related issues on conventional imaging. Six procedures were cancelled due to lack of visualization. MR-guided breast biopsy was performed for 100 mass and 153 nonmass enhancements. Pathology results were classified into benign (113 lesions), high risk (47 lesions), and malignant (40 ductal carcinoma in situ, 38 invasive ductal carcinoma, 15 invasive lobular carcinoma). Subsequent surgery for high risk and malignant findings revealed an underestimation rate of 34% (16/47) for high risk lesions and of 7.5% for ductal carcinoma in situ (3/40). The overall positive predictive value (PPV) was calculated at 43.1% (33.3% for high-risk women, 70.3% for cancer staging, and 37.4% for incidental/undetermined lesions). The PPV was higher for mass (57%) versus nonmass enhancements (34%). MR-guided breast biopsy proved to be a reliable procedure for the diagnosis and management of occult breast MRI findings, or lesions that preclude biopsy under conventional guidance. The PPV displayed significant variation between patient subgroups, correlating higher values with a higher associated breast cancer prevalence.}, } @article {pmid26509909, year = {2017}, author = {Al Nemer, A}, title = {The Performance of Ki-67 Labeling Index in Different Specimen Categories of Invasive Ductal Carcinoma of the Breast Using 2 Scoring Methods.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {25}, number = {2}, pages = {86-90}, doi = {10.1097/PAI.0000000000000268}, pmid = {26509909}, issn = {1533-4058}, mesh = {Biopsy ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Middle Aged ; Prognosis ; Reproducibility of Results ; }, abstract = {In breast carcinoma proliferative rate is not only prognostic, but also predictive factor. Ki-67 labeling index (Ki-67 LI) is a superior and more reproducible way to assess proliferation than counting mitoses. There are different Ki-67 LI cut-off values proposed for stratification. The best method of scoring Ki-67 LI is still controversial. Our aim was to test the consensus of Ki-67 LI read in the 2 most common specimens, diagnostic core biopsies (CNB) and surgical excision (SE), first using the hot spot (HS) for counting, and then the average (Av) Ki-67 LI. Cases diagnosed as having invasive duct breast carcinoma on CNB followed by SE over 6 years were recruited (n=96). Ki-67 LI was counted in both specimen types using HS and Av scoring methods. For both methods, agreement between the 2 specimen categories was tested using different cut-off values. Intraobserver reproducibility was also measured for both scoring methods. Ki-67 LI was significantly lower in CNBs compared with SEs (mean difference: -13.3 and -6.3, P<0.001, using HS and Av methods, respectively). The agreement between Ki-67 LI in CNBs and SEs using 10, 14, and 20 as cut-off value was superior when we used Av method (for κ=0.793, 0.814, and 0.745; vs. for HS: κ=0.542, 0.525, and 0.672, respectively). Intraobserver reproducibility ranged from very good to perfect for both methods. Our results suggested that specimen-specific cut-off value should be applied for both scoring methods.}, } @article {pmid26505860, year = {2016}, author = {Ni, J and Tang, P}, title = {An Unusual Bone Metastasis Mimicking SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) Syndrome on Bone Scintigraphy.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {2}, pages = {173-175}, doi = {10.1097/RLU.0000000000001061}, pmid = {26505860}, issn = {1536-0229}, mesh = {Acquired Hyperostosis Syndrome/*diagnostic imaging ; Bone Neoplasms/*diagnostic imaging/secondary ; Breast Neoplasms/diagnostic imaging/*pathology ; Diagnostic Errors ; Female ; Humans ; Middle Aged ; Radionuclide Imaging ; }, abstract = {The costosternoclavicular region is not a common bone metastasis site, and symmetrical involvement is even rarer. Increased tracer uptake in the manubrium and sternoclavicular joints usually gives the typical "bull-horn" appearance seen in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Herein, we report a case of a 47-year-old woman with a history of invasive ductal carcinoma who had undergone left radical mastectomy 3 years earlier and presented with typical increased tracer uptake in the bilateral sternocostoclavicular region resembling the so-called bull horn. The final diagnosis of metastasis from breast cancer was made histopathologically following biopsy.}, } @article {pmid26503945, year = {2016}, author = {Podo, F and Santoro, F and Di Leo, G and Manoukian, S and de Giacomi, C and Corcione, S and Cortesi, L and Carbonaro, LA and Trimboli, RM and Cilotti, A and Preda, L and Bonanni, B and Pensabene, M and Martincich, L and Savarese, A and Contegiacomo, A and Sardanelli, F}, title = {Triple-Negative versus Non-Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {22}, number = {4}, pages = {895-904}, doi = {10.1158/1078-0432.CCR-15-0459}, pmid = {26503945}, issn = {1557-3265}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/*diagnosis/genetics/mortality/therapy ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Middle Aged ; Mutation ; Phenotype ; Risk ; Treatment Outcome ; Triple Negative Breast Neoplasms/*diagnosis/genetics/mortality/therapy ; }, abstract = {PURPOSE: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women.

EXPERIMENTAL DESIGN: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up.

RESULTS: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P < 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 ± 5 mm versus 12 ± 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86% ± 9% for TNBCs versus 93% ± 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% ± 12% versus 76% ± 8% (P = 0.216).

CONCLUSIONS: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced.}, } @article {pmid26500844, year = {2015}, author = {Okun, JG and Conway, S and Schmidt, KV and Schumacher, J and Wang, X and de Guia, R and Zota, A and Klement, J and Seibert, O and Peters, A and Maida, A and Herzig, S and Rose, AJ}, title = {Molecular regulation of urea cycle function by the liver glucocorticoid receptor.}, journal = {Molecular metabolism}, volume = {4}, number = {10}, pages = {732-740}, pmid = {26500844}, issn = {2212-8778}, abstract = {OBJECTIVE: One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function.

METHODS: Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices.

RESULTS: A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR.

CONCLUSIONS: The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.}, } @article {pmid26496323, year = {2015}, author = {Cheung, YC and Juan, YH and Ueng, SH and Lo, YF and Huang, PC and Lin, YC and Chen, SC}, title = {Assessment of Breast Specimens With or Without Calcifications in Diagnosing Malignant and Atypia for Mammographic Breast Microcalcifications Without Mass: A STARD-Compliant Diagnostic Accuracy Article.}, journal = {Medicine}, volume = {94}, number = {42}, pages = {e1832}, pmid = {26496323}, issn = {1536-5964}, mesh = {Adult ; Aged ; Biopsy, Needle/methods ; Breast Diseases/*diagnostic imaging/*pathology ; Breast Neoplasms/*diagnostic imaging/*pathology ; Calcinosis/*diagnostic imaging/*pathology ; Female ; Humans ; *Mammography ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {Presence of microcalcifications within the specimens frequently signifies a successful attempt of stereotactic vacuum-assisted breast biopsy (VABB) in obtaining a pathologic diagnosis of the breast microcalcifications. In this study, the authors aimed to assess and compare the accuracy and consistency of calcified or noncalcified specimens obtained from same sites of sampling on isolated microcalcifications without mass in diagnosing high-risk and malignant lesions. To the best of our knowledge, an individual case-based prospective comparison has not been reported.With the approval from institutional review board of our hospital (Chang Gung Memorial Hospital), the authors retrospectively reviewed all clinical cases of stereotactic VABBs on isolated breast microcalcifications without mass from our database. The authors included those having either surgery performed or had clinical follow-up of at least 3 years for analysis. All the obtained specimens with or without calcification were identified using specimen radiographs and separately submitted for pathologic evaluation. The concordance of diagnosis was assessed for both atypia and malignant lesions.A total of 390 stereotactic VABB procedures (1206 calcified and 1456 noncalcified specimens) were collected and reviewed. The consistent rates between calcified and noncalcified specimens were low for atypia and malignant microcalcifications (44.44% in flat epithelial atypia, 46.51% in atypical ductal hyperplasia, 55.73% in ductal carcinoma in situ, and 71.42% in invasive ductal carcinoma). The discordance in VABB diagnoses indicated that 41.33% of malignant lesions would be misdiagnosed by noncalcified specimens. Furthermore, calcified specimens showed higher diagnostic accuracy of breast cancer as compared with the noncalcified specimens (91.54 % versus 69.49%, respectively). The evaluation of both noncalcified specimens and calcified specimens did not show improvement of diagnostic accuracy as compared with evaluating calcified specimens alone (91.54% versus 91.54%, respectively).The high prevalence of diagnostic discordance between the calcified and noncalcified specimens indicated the higher value of calcified specimens in diagnosing atypia and malignant microcalcifications. Noncalcified specimens did not provide additional diagnostic benefit from this study. The separation of calcified and noncalcified specimens may facilitate more focused interpretation from pathologists among the large number of specimens.}, } @article {pmid26492903, year = {2015}, author = {Hadjiminas, DJ and Zacharioudakis, KE and Tasoulis, MK and Hu, JC and Lanitis, S and Bright-Thomas, R and Dimopoulos, NG and Hornzee, G and Cunningham, DA and Cleator, SJ and Al Mufti, R}, title = {Adequacy of diagnostic tests and surgical management of symptomatic invasive lobular carcinoma of the breast.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {97}, number = {8}, pages = {578-583}, pmid = {26492903}, issn = {1478-7083}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Lobular/*diagnosis/surgery ; Female ; Humans ; Mammography/*methods ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasm Staging ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Ultrasonography, Mammary/methods ; }, abstract = {INTRODUCTION: Invasive lobular carcinoma (ILC) presents diagnostic and therapeutic challenges as it produces subtle radiological changes. It has been suggested that it is not suitable for breast conserving surgery (BCS). The aim of this study was to ascertain the diagnostic adequacy of modern mammography and ultrasonography in the context of a fast track symptomatic diagnostic clinic in the UK. It also sought to compare the mastectomy, re-excision and BCS rates for ILC with those for invasive ductal carcinoma (IDC).

METHODS: A retrospective analysis of prospectively collected data was carried out on all new symptomatic cancers presenting to the one-stop diagnostic clinic of a single breast unit between 1998 and 2007.

RESULTS: Compared with IDC, ILC was significantly larger at presentation (46mm vs 25mm), needed re-excision after BCS more often (38.8% vs 22.3%) and required mastectomy more frequently (58.8% vs 40.8%). Although mammography performs poorly in diagnosing ILC compared with IDC, when combined with ultrasonography, sensitivity of the combined imaging was not significantly different between these two histological types.

CONCLUSIONS: Provided ultrasonography is performed, standard radiological imaging is adequate for initial diagnosis of symptomatically presenting ILC but some additional preoperative workup should clearly be employed to reduce the higher number of reoperations for this histological type.}, } @article {pmid26491255, year = {2015}, author = {Su, Y and Wang, X and Li, J and Xu, J and Xu, L}, title = {The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.}, journal = {Drug design, development and therapy}, volume = {9}, number = {}, pages = {5439-5445}, pmid = {26491255}, issn = {1177-8881}, mesh = {Acid Anhydride Hydrolases/*genetics/metabolism ; Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*drug therapy/enzymology/*genetics/pathology ; Carcinoma, Ductal, Breast/*drug therapy/enzymology/*genetics/pathology ; Chi-Square Distribution ; DNA Methylation/*drug effects ; Drug Discovery/*methods ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Molecular Targeted Therapy ; Neoplasm Proteins/*genetics/metabolism ; Neoplasm Staging ; Odds Ratio ; Risk Factors ; Signal Transduction/drug effects ; }, abstract = {FHIT is a bona fide tumor-suppressor gene and its loss contributes to tumorigenesis of epithelial cancers including breast cancer (BC). However, the association and clinicopathological significance between FHIT promoter hypermethylation and BC remains unclear. The purpose of this study is to conduct a meta-analysis and literature review to investigate the clinicopathological significance of FHIT methylation in BC. A detailed literature search was performed in PubMed, EMBASE, Web of Science, and Google Scholar databases. The data were extracted and assessed by two reviewers independently. Odds ratios with 95% corresponding confidence intervals were calculated. A total of seven relevant articles were available for meta-analysis, which included 985 patients. The frequency of FHIT hypermethylation was significantly increased in invasive ductal carcinoma compared to benign breast disease, the pooled odds ratio was 8.43, P<0.00001. The rate of FHIT hypermethylation was not significantly different between stage I/II and stage III/IV, odds ratio was 2.98, P=0.06. In addition, FHIT hypermethylation was not significantly associated with ER and PR status. FHIT hypermethylation was not significantly correlated with premenopausal and postmenopausal patients with invasive ductal carcinoma. In summary, our meta-analysis indicated that the frequency of FHIT hypermethylation was significantly increased in BC compared to benign breast disease. The rate of FHIT hypermethylation in advanced stages of BC was higher than in earlier stages; however, the difference was not statistically significant. Our data suggested that FHIT methylation could be a diagnostic biomarker of BC carcinogenesis. FHIT is a potential drug target for development of demethylation treatment for patients with BC.}, } @article {pmid26489679, year = {2015}, author = {Saluja, K and Sahoo, S}, title = {Invasive Paget Disease of the Nipple of Luminal-B Subtype With Axillary Lymph Node Metastasis in a 60-Year-Old White Woman.}, journal = {Laboratory medicine}, volume = {46}, number = {4}, pages = {332-337}, doi = {10.1309/LM00DUW2SRHOSUWD}, pmid = {26489679}, issn = {1943-7730}, mesh = {*Breast Neoplasms ; Female ; Humans ; Lymph Nodes/*pathology ; Middle Aged ; Nipples/*pathology ; *Paget's Disease, Mammary ; Sentinel Lymph Node Biopsy ; }, abstract = {Herein, we report a rare case of invasive Paget disease of the nipple with axillary-lymph-node metastasis in a 60-year-old white woman. The patient had intermittent, bloody nipple discharge without skin changes of the nipple-areolar region. We considered the clinical diagnosis of intraductal papilloma. A subareolar core biopsy revealed invasive ductal carcinoma in deep dermal tissue without the overlying epidermis biopsied. The patient underwent total mastectomy and axillary sentinel lymph-node biopsy that demonstrated invasive Paget disease of the nipple with 3.5-mm depth of invasion, ductal carcinoma in-situ in the underlying breast parenchyma, and macrometastasis (5.0 mm) in the sentinel lymph node. Prognostic marker studies of the metastatic site revealed a profile similar to that in the invasive mammary Paget disease (estrogen receptor [ER]+/progesterone receptor [PR]+/human epidermal growth factor receptor 2 [HER2]-/proliferation index [Ki-67] of 30%). The patient received adjuvant chemotherapy and experienced no disease recurrence at 20-months of follow-up. This case of luminal-B subtype invasive Paget disease as the source of regional metastasis is unique in the literature, to our knowledge.}, } @article {pmid26489549, year = {2015}, author = {Takayanagi, H and Hayami, R and Tsuneizumi, M and Nakagami, K}, title = {[Thrombophlebitis in an Elderly Japanese Woman Treated with Tamoxifen for Breast Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {42}, number = {10}, pages = {1203-1205}, pmid = {26489549}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Antineoplastic Agents, Hormonal/*adverse effects/therapeutic use ; Biopsy ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Staging ; Tamoxifen/*adverse effects/therapeutic use ; Thrombophlebitis/*chemically induced/diagnostic imaging ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {In this study, we report the rare case of an elderly woman who developed thrombophlebitis after being treated with tamoxifen for breast cancer. She visited our department with a lump in her left breast. She underwent core needle biopsy, and she was diagnosed with breast cancer (invasive ductal carcinoma, ER- and PgR-positive, HER2-negative). We chose hormonal therapy because surgical treatment was deemed too invasive considering her general status. She was administered tamoxifen (20 mg/day) instead of an aromatase inhibitor in consideration of her osteoporosis. Six months after initiating tamoxifen therapy, she exhibited swelling in her left leg. Computed tomography and ultrasound revealed thrombophlebitis in her left femoral vein. She stopped taking tamoxifen and started warfarin potassium as thrombolytic therapy, after which thrombophlebitis was relieved. Advanced age may be a risk factor for thrombophlebitis associated with tamoxifen treatment; therefore, precautions should be taken accordingly.}, } @article {pmid26481274, year = {2015}, author = {Ballard, AJ}, title = {Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.}, journal = {Pathology, research and practice}, volume = {211}, number = {12}, pages = {1003-1005}, doi = {10.1016/j.prp.2015.09.017}, pmid = {26481274}, issn = {1618-0631}, mesh = {Breast Neoplasms/*pathology/*virology ; Carcinoma, Ductal, Breast/pathology/*virology ; Carcinoma, Lobular/pathology/*virology ; Epstein-Barr Virus Infections/*complications ; Female ; Humans ; Immunohistochemistry ; Tissue Array Analysis ; }, abstract = {The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types.}, } @article {pmid26475094, year = {2015}, author = {Di Oto, E and Monti, V and Cucchi, MC and Masetti, R and Varga, Z and Foschini, MP}, title = {X chromosome gain in male breast cancer.}, journal = {Human pathology}, volume = {46}, number = {12}, pages = {1908-1912}, doi = {10.1016/j.humpath.2015.08.008}, pmid = {26475094}, issn = {1532-8392}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosomes, Human, X/*genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; }, abstract = {Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer. Twenty cases of male breast invasive ductal carcinoma were retrieved and compared with 10 cases of gynecomastia. Cases were tested by fluorescence in situ hybridization to assess a cytogenetic profile for the X chromosome. The X chromosome status was compared with histopathologic features and stage at presentation. All MBC cases harbored an X chromosome gain (100%) in a variable percentage of neoplastic cells, ranging from 31% to 85% (mean, 59%). On the contrary, all cases of gynecomastia showed wild X chromosome asset. The patients' age at surgery and tumor grading showed a statistically significant correlation (P = .0188-.04), with the percentages of neoplastic cells showing an X chromosome gain. These data suggest that this X chromosome gain plays a role in the neoplastic transformation of male breast epithelial cells.}, } @article {pmid26474389, year = {2015}, author = {Aswad, L and Yenamandra, SP and Ow, GS and Grinchuk, O and Ivshina, AV and Kuznetsov, VA}, title = {Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development.}, journal = {Oncotarget}, volume = {6}, number = {34}, pages = {36652-36674}, pmid = {26474389}, issn = {1949-2553}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Female ; Genome, Human ; Humans ; Middle Aged ; Prognosis ; Transcriptome ; }, abstract = {Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood.We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 patients). We identified a 22-gene tumor aggressiveness grading classifier (22g-TAG) that reflects global bifurcation in the IDC transcriptomes and reclassified patients with HG2 tumors into two genetically and clinically distinct subclasses: histological grade 1-like (HG1-like) and histological grade 3-like (HG3-like). The expression profiles and clinical outcomes of these subclasses were similar to the HG1 and HG3 tumors, respectively. We further reclassified IDC into low genetic grade (LGG = HG1+HG1-like) and high genetic grade (HGG = HG3-like+HG3) subclasses. For the HG1-like and HG3-like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these tumors. We found similar molecular patterns in the LGG and HGG tumor classes respectively.Our results suggest the existence of two genetically-predefined IDC classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of IDC patients.}, } @article {pmid26472981, year = {2015}, author = {Park, CJ and Kim, EK and Woo, HY and Moon, HJ and Yoon, JH and Kim, MJ}, title = {Breast Cancer Arising Adjacent to an Involuting Fibroadenoma: Serial Changes in Radiologic Features.}, journal = {Journal of breast cancer}, volume = {18}, number = {3}, pages = {291-295}, pmid = {26472981}, issn = {1738-6756}, abstract = {Fibroadenoma is a common benign breast lesion and its malignant transformation is rare. There have been several case reports and studies that retrospectively reviewed breast cancers that arose within fibroadenomas; however, none of these studies reported serial changes in radiologic features of the cancer, including findings from mammography and ultrasound (US). We report a case of breast cancer arising adjacent to an involuting fibro adenoma in a 39-year-old woman who was undergoing serial follow-up after her fibroadenoma was diagnosed. Seven years after her diagnosis, the lesion showed evidence of coarse calcifications, a typical sign of involution. Four years later, US revealed a newly developed hypoechoic lesion with irregular margins and peripherally located calcifications adjacent to the fibroadenoma. A core biopsy was performed, and histopathological examination resulted in a diagnosis of invasive ductal carcinoma. When new suspicious features are observed in a fibroadenoma, radiologists should raise the concern for breast cancer and proceed with diagnosis and treatment accordingly.}, } @article {pmid26472980, year = {2015}, author = {Park, JS and Choi, DH and Huh, SJ and Park, W and Kim, YI and Nam, SJ and Lee, JE and Kil, WH}, title = {Comparison of Clinicopathological Features and Treatment Results between Invasive Lobular Carcinoma and Ductal Carcinoma of the Breast.}, journal = {Journal of breast cancer}, volume = {18}, number = {3}, pages = {285-290}, pmid = {26472980}, issn = {1738-6756}, abstract = {PURPOSE: The purpose of this study was to assess the incidence of invasive lobular carcinoma (ILC) and to compare the clinicopathological features and treatment results after breast conserving surgery (BCS) followed by radiotherapy between ILC and invasive ductal carcinoma (IDC).

METHODS: A total of 1,071 patients who underwent BCS followed by radiotherapy were included in the study. Medical records and pathological reports were retrospectively reviewed.

RESULTS: The incidence of ILC was 5.2% (n=56). Bilateral breast cancer, lower nuclear grade, and hormone receptor-positive breast cancer were more frequent in patients with ILC than in those with IDC. There were no cases of lymphovascular invasion or the basal-like subtype in patients with ILC. There were no statistically significant differences in patterns of failure or treatment outcomes between patients with ILC and those with IDC. The development of metachronous contralateral breast cancer was more frequent in patients with IDC (n=27). Only one patient with ILC developed contralateral breast cancer, with a case of ductal carcinoma in situ.

CONCLUSION: The incidence of ILC was slightly higher in our study than in previous Korean studies, but was lower than the incidences reported in Western studies. The differences we observed in clinico pathological features between ILC and IDC were similar to those described elsewhere in the literature. Although there were no statistically significant differences, there was a trend toward better disease-specific survival and disease-free survival rates in patients with ILC than in those with IDC.}, } @article {pmid26472289, year = {2015}, author = {Ressl, N and Oberndorfer, S}, title = {Multiple calcified brain metastases in a man with invasive ductal breast cancer.}, journal = {BMJ case reports}, volume = {2015}, number = {}, pages = {}, pmid = {26472289}, issn = {1757-790X}, mesh = {Brain Neoplasms/*pathology/*secondary ; Breast Neoplasms, Male/*pathology ; Calcinosis/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Humans ; Male ; Middle Aged ; }, abstract = {We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour.}, } @article {pmid26471845, year = {2015}, author = {Lopes, LV and Miguel, F and Freitas, H and Tavares, A and Pangui, S and Castro, C and Lacerda, GF and Longatto-Filho, A and Weiderpass, E and Santos, LL}, title = {Stage at presentation of breast cancer in Luanda, Angola - a retrospective study.}, journal = {BMC health services research}, volume = {15}, number = {}, pages = {471}, pmid = {26471845}, issn = {1472-6963}, mesh = {Adult ; Africa ; Aged ; Aged, 80 and over ; Angola ; Breast Neoplasms/*diagnosis ; Early Detection of Cancer ; Female ; Humans ; Lymph Nodes/pathology ; Medical Audit ; Middle Aged ; *Neoplasm Staging ; Retrospective Studies ; }, abstract = {BACKGROUND: It is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country.

METHODS: Data on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed.

RESULTS: The median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25-89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV).

DISCUSSION: In this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services.

CONCLUSION: Angola needs urgently a program for early diagnosis of breast cancer.}, } @article {pmid26467458, year = {2016}, author = {Merrill, AL and Coopey, SB and Tang, R and McEvoy, MP and Specht, MC and Hughes, KS and Gadd, MA and Smith, BL}, title = {Implications of New Lumpectomy Margin Guidelines for Breast-Conserving Surgery: Changes in Reexcision Rates and Predicted Rates of Residual Tumor.}, journal = {Annals of surgical oncology}, volume = {23}, number = {3}, pages = {729-734}, doi = {10.1245/s10434-015-4916-2}, pmid = {26467458}, issn = {1534-4681}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/surgery ; Carcinoma, Lobular/metabolism/*pathology/surgery ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual/metabolism/*pathology/surgery ; *Practice Guidelines as Topic ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Reoperation ; }, abstract = {BACKGROUND: The 2014 guidelines endorsed by Society of Surgical Oncology, the American Society of Breast Surgeons, and the American Society for Radiation Oncology advocate "no ink on tumor" as the new margin requirement for breast-conserving therapy (BCT). We used our lumpectomy margins database from 2004 to 2006 to predict the effect of these new guidelines on BCT.

METHODS: Patients with neoadjuvant therapy, pure ductal carcinoma-in situ, or incomplete margin data were excluded. We applied new ("no ink on tumor") and old (≥2 mm) margin guidelines and compared rates of positive margins, reexcision, and rates of residual disease found at reexcision.

RESULTS: A total of 437 lumpectomy surgeries met the eligibility criteria. Eighty-six percent had invasive ductal carcinoma, 12% invasive lobular carcinoma, and 2% invasive ductal carcinoma and invasive lobular carcinoma. Using a ≥2 mm margin standard, 36% of lumpectomies had positive margins compared to 18% using new guidelines (p < 0.0001). Seventy-seven percent of patients with "ink on tumor" had residual disease found at reexcision. Fifty percent of subjects with margins <2 mm had residual disease (p = 0.0013) but would not have undergone reexcision under the new guidelines. With margins of ≥2 mm, residual tumor was seen in the shaved margins of 14% of lumpectomies. Residual tumor was more common in reexcisions for ductal carcinoma-in situ <2 mm from a margin than for invasive cancer (53 vs. 40%), although this was not statistically significant.

CONCLUSIONS: Use of new lumpectomy margin guidelines would have reduced reoperation for BCT by half in our patient cohort. However, residual disease was present in many patients who would not have been reexcised with the new guidelines. Long-term follow-up of local recurrence rates is needed to determine if this increase in residual disease is clinically significant.}, } @article {pmid26466985, year = {2016}, author = {Di Rosa, M and Tibullo, D and Saccone, S and Distefano, G and Basile, MS and Di Raimondo, F and Malaguarnera, L}, title = {CHI3L1 nuclear localization in monocyte derived dendritic cells.}, journal = {Immunobiology}, volume = {221}, number = {2}, pages = {347-356}, doi = {10.1016/j.imbio.2015.09.023}, pmid = {26466985}, issn = {1878-3279}, mesh = {Adipokines/genetics/*immunology ; Amino Acid Sequence ; Cell Differentiation ; Cell Nucleus/drug effects/*metabolism ; Chitinase-3-Like Protein 1 ; Dendritic Cells/cytology/drug effects/*immunology ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Lectins/genetics/*immunology ; Macrophages/cytology/drug effects/*immunology ; Models, Molecular ; Molecular Sequence Data ; Monocytes/cytology/drug effects/*immunology ; Primary Cell Culture ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; }, abstract = {Chitinase-3-like-1 protein (CHI3L1) is a glycosyl hydrolase (GH) highly expressed in a variety of inflammatory diseases at infectious and non-infectious etiology. CHI3L1 is produced by a wide variety of cells including monocyte-derived macrophages cell lines such as polarized M1 and M2 type macrophages, osteoclasts and Kupffer cells. In this study we have examined the expression of CHI3L1 during the differentiation and maturation of dendritic cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of dendritic cells in time dependent manner. Furthermore, the CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. These results suggest that CHI3L1 may play crucial role in the DCs immunoresponse.}, } @article {pmid26466947, year = {2016}, author = {Lanzillo, R and Quarantelli, M and Pozzilli, C and Trojano, M and Amato, MP and Marrosu, MG and Francia, A and Florio, C and Orefice, G and Tedeschi, G and Bellantonio, P and Annunziata, P and Grimaldi, LM and Comerci, M and Brunetti, A and Bonavita, V and Alfano, B and Marini, S and Brescia Morra, V and , }, title = {No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {22}, number = {9}, pages = {1163-1173}, doi = {10.1177/1352458515611222}, pmid = {26466947}, issn = {1477-0970}, mesh = {Adult ; Atorvastatin/adverse effects/*therapeutic use ; Atrophy ; Brain/diagnostic imaging/*drug effects/pathology ; Disability Evaluation ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/*therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon beta-1b/adverse effects/*therapeutic use ; Italy ; Magnetic Resonance Imaging ; Male ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging/*drug therapy/pathology ; Neuropsychological Tests ; Patient Dropouts ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis.

OBJECTIVES: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis.

METHODS: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months.

RESULTS: A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months.

CONCLUSIONS: Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis.}, } @article {pmid26464818, year = {2015}, author = {Kazemi-Oula, G and Ghafouri-Fard, S and Mobasheri, MB and Geranpayeh, L and Modarressi, MH}, title = {Upregulation of RHOXF2 and ODF4 Expression in Breast Cancer Tissues.}, journal = {Cell journal}, volume = {17}, number = {3}, pages = {471-477}, pmid = {26464818}, issn = {2228-5806}, abstract = {OBJECTIVE: During the past decade, the importance of biomarker discovery has been highlighted in many aspects of cancer research. Biomarkers may have a role in early detection of cancer, prognosis and survival evaluation as well as drug response. Cancer-testis antigens (CTAs) have gained attention as cancer biomarkers because of their expression in a wide variety of tumors and restricted expression in testis. The aim of this study was to find putative biomarkers for breast cancer.

MATERIALS AND METHODS: In this applied-descriptive study, the expression of 4 CTAs, namely acrosin binding protein (ACRBP), outer dense fiber 4 (ODF4), Rhox homeobox family member 2 (RHOXF2) and spermatogenesis associated 19 (SPATA19) were ana- lyzed at the transcript level in two breast cancer lines (MCF-7 and MDA-MB-231), 40 invasive ductal carcinoma samples and their adjacent normal tissues as well as 10 fibroadenoma samples by means of quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTS: All four genes were expressed in both cell lines. Expression of ODF4 and RH- OXF2 was detected in 62.5% and 60% of breast cancer tissues but in 22.5 and 17.5% of normal tissues examined respectively. The expression of both RHOXF2 and ODF4 was upregulated in cancerous tissues compared with their normal adjacent tissues by 3.31 and 2.96-fold respectively. The expression of both genes was correlated with HER2/neu overexpression. RHOXF2 expression but not ODF4 was correlated with higher stages of tumors. However, no significant association was seen between expression patterns and estrogen and progesterone receptors status.

CONCLUSION: ODF4 and RHOXF2 are proposed as putative breast cancer biomarkers at the transcript level. However, their expression at protein level should be evaluated in future studies.}, } @article {pmid26464707, year = {2015}, author = {Romanska, HM and Potemski, P and Kusinska, R and Kopczynski, J and Sadej, R and Kordek, R}, title = {Expression of CD151/Tspan24 and integrin alpha 3 complex in aid of prognostication of HER2-negative high-grade ductal carcinoma in situ.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {8}, pages = {9471-9478}, pmid = {26464707}, issn = {1936-2625}, mesh = {Breast Neoplasms/*diagnosis/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/pathology ; Female ; Humans ; Integrin alpha3/*metabolism ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/*metabolism ; Tetraspanin 24/*metabolism ; }, abstract = {The pro-tumorigenic and pro-metastatic functions of the tetraspanin protein CD151 (Tspan24) are thought to be dependent on its ability to form complexes with laminin-binding integrin receptors (i.e. alpha6beta1, alpha3beta1, alpha6beta4). We have previously reported that in invasive ductal carcinoma (IDC), CD151/alpha3beta1 complex was of prognostic value in patients with HER2-negative tumors. Extrapolating these findings to the pre-invasive setting, we aimed to make an assessment of a potential relationship between expression of the CD151/alpha3beta1 complex in DCIS and Van Nuys prognostic index (VNPI) in high-grade ductal carcinoma in situ (DCIS) in relation to the HER2 status. Protein distributions were analyzed in 49 samples of pure DCIS using immunohistochemistry. For each case immunoreactivity was assessed in at least 5 ducts (325 ducts in total) and an average score was taken for statistical analyses. When analyzed in the whole cohort, there was no statistical association between the VNPI and any of the proteins scored either separately or in combination. When stratified according to the HER2 status, in the HER2-negative subgroup, CD151 assessed in combination with alpha3beta1 was significantly correlated with VNPI (P = 0.044), while neither protein analyzed individually showed any significant link with the prognostic index. Expression of the CD151/alpha3beta1 complex in HER2-negative DCIS might reflect tumor behavior relevant to the patient outcome and thus might aid prognostication of the disease.}, } @article {pmid26463438, year = {2016}, author = {Gayarre, J and Kamieniak, MM and Cazorla-Jiménez, A and Muñoz-Repeto, I and Borrego, S and García-Donas, J and Hernando, S and Robles-Díaz, L and García-Bueno, JM and Ramón Y Cajal, T and Hernández-Agudo, E and Heredia Soto, V and Márquez-Rodas, I and Echarri, MJ and Lacambra-Calvet, C and Sáez, R and Cusidó, M and Redondo, A and Paz-Ares, L and Hardisson, D and Mendiola, M and Palacios, J and Benítez, J and García, MJ}, title = {The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.}, journal = {Journal of gynecologic oncology}, volume = {27}, number = {1}, pages = {e7}, pmid = {26463438}, issn = {2005-0399}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/genetics ; Carcinoma, Ovarian Epithelial ; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology ; Ovarian Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; Tumor Cells, Cultured ; }, abstract = {OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.

METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays.

RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells.

CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.}, } @article {pmid26462227, year = {2015}, author = {Klomek, AB and Sourander, A and Elonheimo, H}, title = {Bullying by peers in childhood and effects on psychopathology, suicidality, and criminality in adulthood.}, journal = {The lancet. Psychiatry}, volume = {2}, number = {10}, pages = {930-941}, doi = {10.1016/S2215-0366(15)00223-0}, pmid = {26462227}, issn = {2215-0374}, mesh = {Adult ; *Bullying ; Child ; Child, Preschool ; Crime Victims ; *Criminal Behavior ; Female ; Humans ; Male ; Neurodevelopmental Disorders/*epidemiology/*psychology ; Patient Outcome Assessment ; *Peer Group ; Suicide/*psychology ; }, abstract = {Bullying is shown to be associated with adverse outcomes in cross-sectional studies, but only a few studies have prospectively examined the effects of childhood bullying on adult outcomes. Our Series paper focuses on prospective longitudinal studies that used large, population-based, community samples analysed through quantitative methods and published between 1960 and 2015. We describe the results of childhood bullying in adulthood in three of the most burdensome areas: psychopathology, suicidality, and criminality. We note that the different groups involved (ie, victims, bullies, and bully-victims) are at risk of difficulties later in life, but their risk profiles differ and the contributions are probably not independent. Controlling for confounders reduces the risk and sometimes eliminates it. Victims are at a high risk of internalising disorders. Bullies seem to be at risk of later externalising disorders and criminality, mainly violent crime and illicit drug misuse. Bully-victims seem to be at risk of internalising disorders, externalising disorders, and criminality, but not all studies examined bully-victims as a separate group. Boys and girls differ in their long-term outcomes. A dose effect exists in which frequent bullying involvement in childhood is most strongly associated with adult adversities. Future studies need to control for additional factors (including genetic, psychosocial, and environmental) to account for the mechanisms behind the reported longitudinal associations.}, } @article {pmid26458811, year = {2015}, author = {Johns, TS and Yee, J and Smith-Jules, T and Campbell, RC and Bauer, C}, title = {Interdisciplinary care clinics in chronic kidney disease.}, journal = {BMC nephrology}, volume = {16}, number = {}, pages = {161}, pmid = {26458811}, issn = {1471-2369}, mesh = {Advance Care Planning ; Diet ; Humans ; *Interdisciplinary Communication ; Kidney Transplantation ; Mental Health Services ; Patient Care Team/*organization & administration ; Patient Education as Topic ; *Patient-Centered Care ; Quality Improvement ; Renal Insufficiency, Chronic/psychology/*therapy ; Renal Replacement Therapy ; }, abstract = {The burden of chronic kidney disease (CKD) is substantial, and is associated with high hospitalization rates, premature deaths, and considerable health care costs. These factors provide strong rationale for quality improvement initiatives in CKD care. The interdisciplinary care clinic (IDC) has emerged as one solution to improving CKD care. The IDC team may include other physicians, advanced practice providers, nurses, dietitians, pharmacists, and social workers--all working together to provide effective care to patients with chronic kidney disease. Studies suggest that IDCs may improve patient education and preparedness prior to kidney failure, both of which have been associated with improved health outcomes. Interdisciplinary care may also delay the progression to end-stage renal disease and reduce mortality. While most studies suggest that IDC services are likely cost-effective, financing IDCs is challenging and many insurance providers do not pay for all of the services. There are also no robust long-term studies demonstrating the cost-effectiveness of IDCs. This review discusses IDC models and its potential impact on CKD care as well as some of the challenges that may be associated with implementing these clinics.}, } @article {pmid26458308, year = {2015}, author = {Yue, X and Xiao, L and Yang, Y and Liu, W and Zhang, K and Shi, G and Zhou, H and Geng, J and Ning, X and Wu, J and Zhang, Q}, title = {High cytoplasmic expression of SALL4 predicts a malignant phenotype and poor prognosis of breast invasive ductal carcinoma.}, journal = {Neoplasma}, volume = {62}, number = {6}, pages = {980-988}, doi = {10.4149/neo_2015_119}, pmid = {26458308}, issn = {0028-2685}, abstract = {Sal-like 4(SALL4) is significant for maintaining self-renewal and pluripotency in embryonic stem cells, cancer cells and perhaps even cancer stem cells. The expression of SALL4 has been recorded in various kinds of cancers and is deemed to have a clinical value for diagnosis. However, little information on SALL4 expression has been illustrated in breast cancer. In this study, the expression of SALL4 was scrutinized by immunohistochemical analysis in breast invasive ductal carcinoma in a large cohort of 160 patients. High cytoplasmic expression of SALL4 was detected in breast cancer tissues compared with normal adjacent tissues. High SALL4 expression was associated with advanced tumor invasion (p = 0.019), lymph node stage (p = 0.027), ER (p = 0.030), PR (p = 0.037), HER2 (p = 0.019) and TNBC (p = 0.007) in overall patients. Interestingly, in Kaplan-Meier analysis, breast cancer patients with high expression of SALL4 demonstrated a worse OS. Both univariate and multivariate analysis illustrated that examination of SALL4 was of great prognostic value in OS. Thus, our data showed that high cytoplasmic expression of SALL4 was considered to be an independent prognostic indicator for breast invasive ductal carcinoma.}, } @article {pmid26454450, year = {2016}, author = {Shoshani, A and Mifano, K and Czamanski-Cohen, J}, title = {The effects of the Make a Wish intervention on psychiatric symptoms and health-related quality of life of children with cancer: a randomised controlled trial.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {25}, number = {5}, pages = {1209-1218}, pmid = {26454450}, issn = {1573-2649}, support = {R25 CA078447/CA/NCI NIH HHS/United States ; }, mesh = {Child ; Depression/psychology ; Depressive Disorder/psychology ; Female ; *Hope ; Humans ; Israel ; Male ; Mental Health ; Neoplasms/*psychology/therapy ; Quality of Life/*psychology ; *Self-Help Groups ; *Social Support ; }, abstract = {OBJECTIVE: Children with life-threatening medical conditions frequently undergo invasive medical procedures that may elicit anxiety and distress. However, there are few empirically validated interventions that reduce mental health symptoms and increase the resilience of children during the acute stages of illness. This study aimed to evaluate the efficacy of the Make a Wish intervention for children with life-threatening cancer.

METHODS: The design was a wait-list-controlled trial with two parallel groups. Sixty-six children aged 5-12 with an initial diagnosis of life-threatening cancer were identified and randomly assigned to the Make a Wish intervention (n = 32) or a wait-list control group (n = 34). Children completed measures of psychiatric and health-related symptoms, positive and negative affect, hope, and optimism pre-intervention and post-intervention. After baseline data collection, children were interviewed and made an authentic wish that they wanted to come true. These wishes were made possible 5-6 months after baseline data collection, to fuel anticipation and excitement over the wish-fulfillment event. The post-intervention assessment point was 5 weeks after wish fulfillment (approximately 7 months after baseline data collection).

RESULTS: Children in the intervention group exhibited a significant reduction in general distress (d = 0.54), depression (d = 0.70), and anxiety symptoms (d = 0.41), improved health-related quality of life (d = 0.59), hope (d = 0.71), and positive affect (d = 0.80) compared to decrease in positive affect and no significant changes in the other measures in the control group.

CONCLUSIONS: These findings emphasize the role of hope and positive emotions in fostering the well-being of children who suffer from serious illnesses.}, } @article {pmid26453841, year = {2016}, author = {Vogel, M and Schmitz, RP and Hagel, S and Pletz, MW and Gagelmann, N and Scherag, A and Schlattmann, P and Brunkhorst, FM}, title = {Infectious disease consultation for Staphylococcus aureus bacteremia - A systematic review and meta-analysis.}, journal = {The Journal of infection}, volume = {72}, number = {1}, pages = {19-28}, doi = {10.1016/j.jinf.2015.09.037}, pmid = {26453841}, issn = {1532-2742}, mesh = {Aged ; Bacteremia/*epidemiology/mortality ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Quality Indicators, Health Care/*statistics & numerical data ; Referral and Consultation/*statistics & numerical data ; Staphylococcal Infections/*epidemiology/mortality ; *Staphylococcus aureus ; }, abstract = {OBJECTIVE: Mortality and morbidity of Staphylococcus aureus bacteremia (SAB) still remains considerably high. We aimed to evaluate the impact of infectious disease consultation (IDC) on the management and outcomes of patients with SAB.

METHODS: We systematically searched 3 publication databases from inception to 31st May 2015 and reference lists of identified primary studies.

RESULTS: Our search returned 2874 reports, of which 18 fulfilled the inclusion criteria, accounting for 5337 patients. Overall 30-day mortality was 19.95% [95% CI 14.37-27.02] with a significant difference in favour of the IDC group (12.39% vs 26.07%) with a relative risk (RR) of 0.53 [95% CI 0.43-0.65]. 90-day mortality and relapse risk for SAB were also reduced significantly with RRs of 0.77 [95% CI 0.64-0.92] and 0.62 [95% CI 0.39-0.99], respectively. Both, the appropriateness of antistaphylococcal agent and treatment duration was improved by IDC (RR 1.14 [95% CI 1.08-1.20] and 1.85 [95% CI 1.39-2.46], respectively). Follow-up blood cultures and echocardiography were performed more frequently following IDC (RR 1.35 [95% CI 1.25-1.46] and 1.98 [95% CI 1.66-2.37], respectively).

CONCLUSIONS: Evidence-based clinical management enforced by IDC may improve outcome of patients with SAB. Well-designed cluster-randomized controlled trials are needed to confirm this finding from observational studies.}, } @article {pmid26453014, year = {2015}, author = {Webster, BL and Rabone, M and Pennance, T and Emery, AM and Allan, F and Gouvras, A and Knopp, S and Garba, A and Hamidou, AA and Mohammed, KA and Ame, SM and Rollinson, D and Webster, JP}, title = {Erratum to: Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.}, journal = {Parasites & vectors}, volume = {8}, number = {}, pages = {519}, pmid = {26453014}, issn = {1756-3305}, abstract = {Unfortunately, the original version of this article [1], contained a mistake. In Table 1, the primers for Sh6 and Sh9 were included incorrectly. Instead of GGGATGTATGCAGACTTG TTGTTTGGCTGCAGTAAC and GCTGAGCTTGAGATTG CTTCTGTCCCATCGATACC they should have been Sh6 Forward Primer GGTGGATTACGCAATAG, Sh6 Reverse Primer TTTAATCAACCGGGTGTC and Sh9 Forward Primer GGGATGTATGCAGACTTG, Sh9 Reverse Primer TTGTTTGGCTGCAGTAAC respectively. A corrected version of Table 1 is included below}, } @article {pmid26451490, year = {2015}, author = {Ciriello, G and Gatza, ML and Beck, AH and Wilkerson, MD and Rhie, SK and Pastore, A and Zhang, H and McLellan, M and Yau, C and Kandoth, C and Bowlby, R and Shen, H and Hayat, S and Fieldhouse, R and Lester, SC and Tse, GM and Factor, RE and Collins, LC and Allison, KH and Chen, YY and Jensen, K and Johnson, NB and Oesterreich, S and Mills, GB and Cherniack, AD and Robertson, G and Benz, C and Sander, C and Laird, PW and Hoadley, KA and King, TA and , and Perou, CM}, title = {Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.}, journal = {Cell}, volume = {163}, number = {2}, pages = {506-519}, pmid = {26451490}, issn = {1097-4172}, support = {P50-CA58223-09A1/CA/NCI NIH HHS/United States ; R00 CA166228/CA/NCI NIH HHS/United States ; K22 LM011931/LM/NLM NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U24 CA143848/CA/NCI NIH HHS/United States ; F30 CA192725/CA/NCI NIH HHS/United States ; U24 CA143867/CA/NCI NIH HHS/United States ; K99 CA166228/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; R01 CA180006/CA/NCI NIH HHS/United States ; U24 CA143858/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cadherins/chemistry/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Lobular/*genetics/metabolism/*pathology ; Female ; Hepatocyte Nuclear Factor 3-alpha/chemistry/genetics/metabolism ; Humans ; Models, Molecular ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oncogene Protein v-akt/metabolism ; Transcriptome ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.}, } @article {pmid26448887, year = {2015}, author = {Upadhyay, R and Butt, QU and Hamaoui, A and Henderson, C and McCalla, S and Gilak, H}, title = {Triple Negative Breast Cancer in Pregnancy and Postpartum: Two Case Reports in Hispanic Women.}, journal = {Case reports in obstetrics and gynecology}, volume = {2015}, number = {}, pages = {856931}, pmid = {26448887}, issn = {2090-6684}, abstract = {Objective. Despite studies suggesting that triple negative breast cancer is more often seen in women of African ancestry, we report here two cases of pregnancy associated triple negative breast cancer in Hispanic women. Cases. Case one is a 37-year-old female para 2-0-0-2, who presented with a left breast mass, at 19 weeks of gestation, the biopsy of which reported an invasive ductal carcinoma, found to be triple receptor negative. The patient underwent chemotherapy during the pregnancy and was delivered with a cesarean at 37 weeks for obstetric indication. After delivery, the patient completed her chemotherapy that was followed by radical mastectomy and radiotherapy. Case two is a 28-year-old female para 6-0-1-5, who presented while breast-feeding with signs and symptoms of mastitis, and an engorged and tender right breast, five months postpartum. However, the sonogram revealed a fluid filled cavity. Aspiration and cytology did not reflect an infection and were negative for malignancy. High suspicion and lack of improvement led to biopsy that identified an invasive ductal carcinoma, found to be triple negative. The patient underwent chemotherapy followed by modified radical mastectomy. Conclusions. Triple negative breast cancer, during pregnancy or postpartum, poses a unique challenge and requires a multidisciplinary team to optimize treatment for these women.}, } @article {pmid26440364, year = {2015}, author = {Cheng, YS and Seibert, O and Klöting, N and Dietrich, A and Straßburger, K and Fernández-Veledo, S and Vendrell, JJ and Zorzano, A and Blüher, M and Herzig, S and Berriel Diaz, M and Teleman, AA}, title = {PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis.}, journal = {PLoS genetics}, volume = {11}, number = {10}, pages = {e1005561}, pmid = {26440364}, issn = {1553-7404}, mesh = {AMP-Activated Protein Kinases/genetics ; Animals ; Dietary Carbohydrates/metabolism ; Energy Metabolism/*genetics ; Glucose/metabolism ; Hepatocytes/metabolism ; Humans ; Insulin Resistance/genetics ; Lipid Metabolism/*genetics ; Lipogenesis/genetics ; Liver/metabolism ; Mice ; Obesity/*genetics/pathology ; Protein Phosphatase 2/*genetics ; Sterol Regulatory Element Binding Protein 1/genetics ; }, abstract = {In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state.}, } @article {pmid26438270, year = {2015}, author = {Kim, TS and Kang, YJ and Kim, JY and Lee, S and Lee, WJ and Sohn, Y and Lee, HW}, title = {Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation.}, journal = {Malaria journal}, volume = {14}, number = {}, pages = {385}, pmid = {26438270}, issn = {1475-2875}, mesh = {Adult ; CD4 Antigens/analysis ; Calgranulin A/*blood ; Enzyme-Linked Immunosorbent Assay ; Forkhead Transcription Factors/analysis ; Humans ; Immune Evasion ; Interleukin-2 Receptor alpha Subunit/analysis ; Malaria, Vivax/*immunology ; Plasmodium vivax/*immunology/physiology ; Serum/chemistry ; T-Lymphocyte Subsets/chemistry/*immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/chemistry/*immunology ; }, abstract = {BACKGROUND: The pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear. This function was investigated in P. vivax-infected patients in this study.

METHODS: The level of S100A8 in the serum was measured with ELISA. Full amino acids of S100A8 were synthesized to verify the functions for maturation of immature dendritic cell (iDC) and evaluation of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) generation by mature DC (mDC).

RESULTS: A higher amount of S100A8 was detected in vivax-infected patients (141.2 ± 61.849 ng/ml, n = 40) compared with normal control group (48.1 ± 27.384 ng/ml, n = 40). The level of S100A8 did not coincide with that of anti-malarial antibody measured by indirect fluorescent antibody test (IFAT) using parasite-infected red blood cells as antigen. Programmed death-ligand 1 (PD-L1) was up-regulated on the surface of iDCs following treatment with synthetic S100A8, not with synthetic MSP-1, AMA-1 and CSP, as compared to the expression seen for non-treated iDCs. The addition of red blood cells of infected patients to iDCs also elevated their surface expression of CD86. However, the serum levels of S100A8 decreased with increase in parasitaemia. DCs matured by sera containing S100A8 generated Treg cells from naïve T cells. The ratio of Treg cells generated was inversely proportional to the concentration of S100A8 in sera.

CONCLUSIONS: Treg cells suppress the activity of cytotoxic T cells, which kill malaria parasites; therefore, the up-regulation of S100A8 in malaria patients may contribute to pathogen immune escape or tolerance.}, } @article {pmid26437542, year = {2015}, author = {Claimon, A and Chuthapisith, S and Samarnthai, N and Pusuwan, P}, title = {Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {98}, number = {8}, pages = {828-832}, pmid = {26437542}, issn = {0125-2208}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*secondary ; Carcinoma, Neuroendocrine/*diagnosis/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; }, abstract = {The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor}, } @article {pmid26431414, year = {2015}, author = {Fennig, S and Brunstein-Klomek, A and Sasson, A and Halifa Kurtzman, I and Hadas, A}, title = {Feasibility of a Dual Evaluation/Intervention Program for Morbidly Obese Adolescents.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {52}, number = {2}, pages = {107-112}, pmid = {26431414}, issn = {2617-2402}, mesh = {Adolescent ; Child ; Cognitive Behavioral Therapy ; Feasibility Studies ; Feeding and Eating Disorders/*diagnosis/*therapy ; Female ; Humans ; Male ; Obesity, Morbid/*diagnosis/*therapy ; *Program Development ; }, abstract = {BACKGROUND: In the absence of evidence-based guidelines for screening adolescent candidates for bariatric surgery, or improving their adherence to preoperative recommendations, we designed a dual-phase multidisciplinary program aiming for observation-based preoperative assessment/ intervention, as well as for post-operative/ conservative follow up.

METHODS: This study focused on the preoperative 3-month phase. Fifteen morbidly obese adolescents attending the eating disorders unit of a pediatric hospital underwent the program protocol consisting of medical examinations/ tests, psychological measures, self-monitoring, tailored diet, physical activity schedule, individual and group cognitive behavior-oriented therapy, and psycho educational parent training.

RESULTS: All patients completed the preoperative phase. Most of them (70%) followed the structured diet with a significant reduction in BMI. The patients complied with self-monitoring, and body dissatisfaction score improved. Parental participation in therapy was poor. Four patients with low adherence were found ineligible for surgery.

CONCLUSIONS: The findings support the feasibility of our dual screening/intervention protocol. Measures to improve parental participation are warranted.}, } @article {pmid26427765, year = {2016}, author = {Vitale, C and Falco, F and Trojano, L and Erro, R and Moccia, M and Allocca, R and Agosti, V and Santangelo, F and Barone, P and Santangelo, G}, title = {Neuropsychological correlates of Pisa syndrome in patients with Parkinson's disease.}, journal = {Acta neurologica Scandinavica}, volume = {134}, number = {2}, pages = {101-107}, doi = {10.1111/ane.12514}, pmid = {26427765}, issn = {1600-0404}, mesh = {Aged ; Attention ; Case-Control Studies ; *Cognition ; Executive Function ; Female ; Humans ; Male ; Memory ; Middle Aged ; Parkinson Disease/*diagnosis ; *Posture ; }, abstract = {BACKGROUND: A complex relationship exists between postural control and cognition in the elderly. Namely, neural mechanisms that are required for the regulation of posture have been variably associated with cognitive dysfunctions. Parkinson's disease (PD) is the second most common neurodegenerative disease among the elderly, and it has been associated with both cognitive and postural abnormalities such as Pisa syndrome (PS). Although its onset has been considered to be multifactorial, the pathophysiological mechanisms underpinning PS are still not fully explained. Until now, no study investigated the possible contribution of cognitive dysfunction to occurrence of PS in PD.

PATIENTS AND METHODS: Twenty PD patients with PS and 20 PD patients without PS were enrolled. All patients with PD underwent neuropsychological battery to assess behavioural disturbances, memory, attention, frontal/executive and visuospatial functions.

RESULTS: The two groups did not differ on demographic features, age at PD onset and disease duration, whereas they significantly differed on UPDRS-Part III, and levodopa-equivalent daily dose (LEDD). MANCOVA with above-mentioned clinical variable as covariates revealed significant differences on tasks tapping verbal long-term memory, and attentional and visuoperceptual abilities between groups. The binary logistic regression revealed that higher LEDD and lower performance on visuospatial task (Benton Judgment of Lines Orientation test) significantly predicted occurrence of PS.

CONCLUSION: Our results revealed a significant association of PS with altered attention and visuoperceptual functions in PD, suggesting that the occurrence of PS may be associated with alteration of both frontal-striatal systems and posterior cortical areas.}, } @article {pmid26426182, year = {2015}, author = {Verma, P and Bansal, N and Khosa, R and Verma, KG and Sachdev, SK and Patwardhan, N and Garg, S}, title = {Correlation of Radiographic Mental Foramen Position and Occulusion in Three Different Indian Populations.}, journal = {The West Indian medical journal}, volume = {64}, number = {3}, pages = {269-274}, pmid = {26426182}, issn = {0043-3144}, abstract = {BACKGROUND: The knowledge of the position of the mental foramen (MF) is important for administering local anaesthesia for diagnostic, surgical or operative procedures.

AIMS: To determine the shape, position, symmetry of MF and its continuity with the inferior dental canal (IDC) on a digital panoramic view and to find its correlation with Angle's molar relations in three Indian subpopulations. The study also determines the correlation of inter-foramen distance in both genders of three Indian subpopulations.

SUBJECTS AND METHODS: One hundred and twenty digital panoramic radiographs were evaluated from three Indian subpopulations (Punjab, Rajasthan and Northeast [NE]). The assessment of occlusion was based on Angle's molar relationships. The data obtained were statistically analysed.

RESULTS: The commonest position of the MF in the Rajasthan and NE populations was position 4 bilaterally, while in the Punjab population, it was position 3 on the right and position 4 on the left side. The majority of the MF was round in shape followed by oval. The mean distance between two MF was highest among the Punjab male population and least among the NE female population. The most frequent pattern of MF continuity with IDC was diffuse in Rajasthan population, separated in NE and continuous in Punjab. Correlation between Angle's molar relation with MF position was significant for Classes I and II but not for Class III. Correlation of inter-foramen distance between genders was highly significant in the NE and Punjab populations.

CONCLUSION: The commonest MF position was aligned with the 1st premolar and between the 1st and 2nd premolar.}, } @article {pmid26425543, year = {2015}, author = {Bai, G and Wu, C and Gao, Y and Shu, G}, title = {Exploring the Functional Disorder and Corresponding Key Transcription Factors in Intraductal Papillary Mucinous Neoplasms Progression.}, journal = {International journal of genomics}, volume = {2015}, number = {}, pages = {197603}, pmid = {26425543}, issn = {2314-436X}, abstract = {This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT), intraductal papillary mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and invasive ductal carcinoma (IDC) samples. And eight clusters of differentially expressed genes (DEGs) with similar expression pattern were detected by k-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs) enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.}, } @article {pmid26425077, year = {2015}, author = {Huang, R and Ding, P and Yang, F}, title = {Clinicopathological significance and potential drug target of CDH1 in breast cancer: a meta-analysis and literature review.}, journal = {Drug design, development and therapy}, volume = {9}, number = {}, pages = {5277-5285}, pmid = {26425077}, issn = {1177-8881}, mesh = {Antigens, CD ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/drug therapy/*genetics/metabolism/mortality/pathology ; Cadherins/*genetics/metabolism ; Carcinoma, Ductal, Breast/drug therapy/*genetics/metabolism/mortality/pathology ; Chi-Square Distribution ; *DNA Methylation ; Drug Design ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Molecular Targeted Therapy ; Odds Ratio ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Risk Factors ; Treatment Outcome ; }, abstract = {CDH1, as a tumor suppressor gene, contributes sporadic breast cancer (BC) progression. However, the association between CDH1 hypermethylation and BC, and its clinicopathological significance remains unclear. We conducted a meta-analysis to investigate the relationship between the CDH1 methylation profile and the major clinicopathological features. A detailed literature was searched through the electronic databases PubMed, Web of Science™, and EMBASE™ for related research publications. The data were extracted and assessed by two reviewers independently. Odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated and summarized respectively. The frequency of CDH1 methylation was significantly higher in invasive ductal carcinoma than in normal breast tissues (OR =5.83, 95% CI 3.76-9.03, P<0.00001). CDH1 hypermethylation was significantly higher in estrogen receptor (ER)-negative BC than in ER-positive BC (OR =0.62, 95% CI 0.43-0.87, P=0.007). In addition, we found that the CDH1 was significantly methylated in HER2-negative BC than in HER2-positive BC (OR =0.26, 95% CI 0.15-0.44, P<0.00001). However, CDH1 methylation frequency was not associated with progesterone receptor (PR) status, or with grades, stages, or lymph node metastasis of BC patients. Our results indicate that CDH1 hypermethylation is a potential novel drug target for developing personalized therapy. CDH1 hypermethylation is strongly associated with ER-negative and HER2-negative BC, respectively, suggesting CDH1 methylation status could contribute to the development of novel therapeutic approaches for the treatment of ER-negative or HER2-negative BC with aggressive tumor biology.}, } @article {pmid26418423, year = {2015}, author = {Romanska, HM and Potemski, P and Krakowska, M and Mieszkowska, M and Chaudhri, S and Kordek, R and Kubiak, R and Speirs, V and Hanby, AM and Sadej, R and Berditchevski, F}, title = {Lack of CD151/integrin α3β1 complex is predictive of poor outcome in node-negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular and ductal breast cancers.}, journal = {British journal of cancer}, volume = {113}, number = {9}, pages = {1350-1357}, pmid = {26418423}, issn = {1532-1827}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry/methods ; Integrin alpha3beta1/*metabolism ; Lymph Nodes/*pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Tetraspanin 24/*metabolism ; }, abstract = {BACKGROUND: The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3β1 in patients with ILC in context of the data of our recent IDC study.

METHODS: Expression of CD151 and/or integrin α3β1 was evaluated in ILC samples (N=117) using immunohistochemistry. The findings were analysed in relation to our results from an IDC cohort (N=182) demonstrating a prognostic value of an expression of CD151/integrin α3β1 complex in patients with HER2-negative tumours.

RESULTS: Unlike in the IDCs, neither CD151 nor CD151/α3β1 complex showed any correlation with any of the ILC characteristics. Lack of both CD151 and α3β1 was significantly correlated with poor survival (P=0.034) in lymph node-negative ILC N(-) cases. The CD151(-)/α3β1(-) patients had 3.12-fold higher risk of death from BCa in comparison with the rest of the ILC N(-) patients.

CONCLUSIONS: Biological role of CD151/α3β1 varies between ILC and IDC. Assessment of CD151/α3β1 might help to identify ILC N(-) patients with increased risk of distant metastases.}, } @article {pmid26417028, year = {2015}, author = {Da Costa, GG and Gomig, TH and Kaviski, R and Santos Sousa, K and Kukolj, C and De Lima, RS and De Andrade Urban, C and Cavalli, IJ and Ribeiro, EM}, title = {Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights Potential Biomarkers in Breast Cancer.}, journal = {Cancer genomics & proteomics}, volume = {12}, number = {5}, pages = {251-261}, pmid = {26417028}, issn = {1790-6245}, mesh = {Adult ; Aged ; *Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology ; Female ; Humans ; Mammary Glands, Human/*metabolism ; Middle Aged ; Neoplasm Grading ; *Proteome ; *Proteomics/methods ; Tumor Burden ; }, abstract = {BACKGROUND/AIM: Breast cancer is the most common type of cancer among women worldwide, and about 57,000 new cases are expected for the Brazilian population in 2015. Elucidation of protein expression and modification is essential for the biological understanding, early diagnosis and therapeutics of breast cancer. The main objectives of the study are comparison between the proteome of tumor and paired non-tumor breast cancer tissues, describing all identified proteins, highlighting the ones most differentially expressed and comparing the data with existing literature.

MATERIALS AND METHODS: The five paired samples from patients with invasive ductal carcinoma were analyzed by 2-DE and MS.

RESULTS: We collected 161 identified spots corresponding to 110 distinct proteins. Forty-three differentially-expressed spots were common to at least two samples, and the ten proteins with the highest-fold changes were CASPE, ENOG, TPM1, CAPG, VIME, TPM3, TRFE, PDIA6, WDR61 and PDIA3. Metabolic enzymes and proteins with binding functions were the most representative functional classes of proteins with increased and decreased expression in tumor tissue respectively.

CONCLUSION: Taking the fold change as a parameter, we point to future targets to be studied by functional methods in a search for biomarkers for initiation and progress of breast cancer.}, } @article {pmid26415633, year = {2015}, author = {Zheng, C and Shao, W and Paidi, SK and Han, B and Fu, T and Wu, D and Bi, L and Xu, W and Fan, Z and Barman, I}, title = {Pursuing shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) for concomitant detection of breast lesions and microcalcifications.}, journal = {Nanoscale}, volume = {7}, number = {40}, pages = {16960-16968}, doi = {10.1039/c5nr05319f}, pmid = {26415633}, issn = {2040-3372}, mesh = {*Breast Neoplasms/diagnosis/metabolism ; *Calcinosis/metabolism/pathology ; Female ; *Gold/chemistry/pharmacology ; Humans ; *Mammary Glands, Human/metabolism/pathology ; Nanoparticles/*chemistry ; *Silicon Dioxide/chemistry/pharmacology ; *Spectrum Analysis, Raman ; }, abstract = {Although tissue staining followed by morphologic identification remains the gold standard for diagnosis of most cancers, such determinations relying solely on morphology are often hampered by inter- and intra-observer variability. Vibrational spectroscopic techniques, in contrast, offer objective markers for diagnoses and can afford disease detection prior to alterations in cellular and extracellular architecture by furnishing a rapid "omics"-like view of the biochemical status of the probed specimen. Here, we report a classification approach to concomitantly detect microcalcification status and local pathological state in breast tissue, featuring a combination of vibrational spectroscopy that focuses on the tumor and its microenvironment, and multivariate data analysis of spectral markers reflecting molecular expression. We employ the unprecedented sensitivity and exquisite molecular specificity offered by Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) to probe the presence of calcified deposits and distinguish between normal breast tissues, fibroadenoma, atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). By correlating the spectra with the corresponding histologic assessment, we developed partial least squares-discriminant analysis derived decision algorithm that provides excellent diagnostic power in the fresh frozen sections (overall accuracy of 99.4% and 93.6% using SHINs for breast lesions with and without microcalcifications, respectively). The performance of this decision algorithm is competitive with or supersedes that of analogous algorithms employing spontaneous Raman spectroscopy while enabling facile detection due to the considerably higher intensity of SHINERS. Our results pave the way for rapid tissue spectral pathology measurements using SHINERS that can offer a novel stain-free route to accurate and economical diagnoses without human interpretation.}, } @article {pmid26410088, year = {2015}, author = {Yang, JZ and Wang, ZX and Ma, LH and Shen, XB and Sun, Y and Hu, DW and Sun, LX}, title = {The organochlorine pesticides residues in the invasive ductal breast cancer patients.}, journal = {Environmental toxicology and pharmacology}, volume = {40}, number = {3}, pages = {698-703}, doi = {10.1016/j.etap.2015.07.007}, pmid = {26410088}, issn = {1872-7077}, mesh = {Adipose Tissue/*chemistry ; Adult ; Aged ; Breast Neoplasms/*blood/metabolism/pathology ; Carcinoma, Ductal, Breast/*blood/metabolism/pathology ; Chlorobenzenes/blood ; Dichlorodiphenyl Dichloroethylene/blood ; Female ; Hexachlorocyclohexane/blood ; Humans ; Hydrocarbons, Chlorinated/*toxicity ; Middle Aged ; Receptors, Estrogen/metabolism ; }, abstract = {Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.}, } @article {pmid26408742, year = {2015}, author = {Meissnitzer, T and Meissnitzer, MW and Seymer, A and Hergan, K and Neureiter, D}, title = {Relative Uptake Factor of Invasive Ductal Breast Cancer in Breast-specific Gamma Imaging as a Surrogate Parameter for Sub-typing.}, journal = {Anticancer research}, volume = {35}, number = {10}, pages = {5671-5677}, pmid = {26408742}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*classification/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*classification/*diagnostic imaging/pathology ; Female ; Follow-Up Studies ; *Gamma Rays ; Humans ; Immunoenzyme Techniques ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Radionuclide Imaging/*methods ; Retrospective Studies ; }, abstract = {AIM: The retrospective evaluation of correlations between semi-quantitative breast-specific gamma imaging (BSGI) and invasive ductal breast cancer (IDC) sub-types.

MATERIALS AND METHODS: The biopsy specimen of 50 histologically-proven IDCs were retrospectively evaluated concerning receptor status, human epidermal growth factor receptor 2 (HER2/Neu) status, Ki-67 level and classification into IDC sub-types. These results were compared to the relative uptake factor (RUF) in BSGI. Depending on RUF, we described four categories to outline the predictive value of RUF.

RESULTS: A total of 50 IDCs with a mean diameter of 20.36 mm were included. RUF differed reliably between luminal-A and non-luminal-A IDCs. RUF exceeding 6.5 pointed to non luminal A-carcinoma, with a specificity and positive predictive value of 100%. RUF of less than 2.6 was unlikely to be associated with a non-luminal A-carcinoma (negative predictive value: 76.5%). Comparable results were calculated for the correlation between RUF and the K-67 level.

CONCLUSION: RUF may help classify the sub-type of an IDC in addition to pathology.}, } @article {pmid26408705, year = {2015}, author = {Ozturk, T and Kucukhuseyin, O and Eronat, AP and Tuzuner, MB and Daglar-Aday, A and Saygili, N and Kisakesen, HI and Seyhan, F and Velidedeoğlu, M and Calay, Z and Ilvan, Ş and Yilmaz-Aydoğan, H and Ozturk, O and Isbir, T}, title = {Preliminary Study: Prominent miRNAs of Breast Malignant Tissues Compared to Normal Tissues in Turkish Patients with Breast Cancer.}, journal = {Anticancer research}, volume = {35}, number = {10}, pages = {5425-5432}, pmid = {26408705}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Turkey ; }, abstract = {miRNA involvement has been observed in almost every type of cancer, including breast cancer. The etiology of abnormal expression of miRNAs in cancer is still not clearly understood. In order to obtain insight into miRNA de-regulation in breast cancer, we analyzed expression levels of five breast cancer-related miRNAs, miRNA21, miRNA155, miRNA19a, miRNA17-5p and let7a miRNA, in both malignant and neighboring non-tumoral paraffin-embedded tissues of 47 patients with invasive ductal breast cancer. The targeted miRNAs, and a reference snRNA, U6, were analyzed by real-time polymerase chain reaction. let7a Levels were significantly lower in patients with lymphatic invasion than in those without (p=0.047). miR21 was down-regulated in 93.3% of patients with necrosis [p=0.017 (Fisher's exact test (FE))], while at least one oncogenic miRNA was up-regulated in 87.3% of the patients with invasive ductal carcinoma [p=0.009 (FE)]. In addition, tumor-suppressor miRNA was down-regulated or unaltered in 65.8% of the patients with tumor grade 2 or 3 and in all with grade 1 [p=0.047 (FE)]. Based on this preliminary study, we suggest that these miRNAs, especially let7a and miRNA21, might be useful markers in follow-up of breast cancer and in prognosis.}, } @article {pmid26404623, year = {2015}, author = {Nestal de Moraes, G and Delbue, D and Silva, KL and Robaina, MC and Khongkow, P and Gomes, AR and Zona, S and Crocamo, S and Mencalha, AL and Magalhães, LM and Lam, EW and Maia, RC}, title = {FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance.}, journal = {Cellular signalling}, volume = {27}, number = {12}, pages = {2496-2505}, doi = {10.1016/j.cellsig.2015.09.013}, pmid = {26404623}, issn = {1873-3913}, support = {A12011/CRUK_/Cancer Research UK/United Kingdom ; BBS/B/03785/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antibiotics, Antineoplastic/pharmacology ; Base Sequence ; Binding Sites ; Breast Neoplasms/drug therapy/metabolism/mortality ; Cell Survival ; Docetaxel ; Doxorubicin/pharmacology ; *Drug Resistance, Neoplasm ; Female ; Forkhead Box Protein M1 ; Forkhead Transcription Factors/*physiology ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins/genetics/*metabolism ; Kaplan-Meier Estimate ; MCF-7 Cells ; Middle Aged ; Prognosis ; Promoter Regions, Genetic ; Protein Binding ; Survivin ; Taxoids/pharmacology ; X-Linked Inhibitor of Apoptosis Protein/genetics/*metabolism ; }, abstract = {Drug resistance is a major hurdle for successful treatment of breast cancer, the leading cause of deaths in women throughout the world. The FOXM1 transcription factor is a potent oncogene that transcriptionally regulates a wide range of target genes involved in DNA repair, metastasis, cell invasion, and migration. However, little is known about the role of FOXM1 in cell survival and the gene targets involved. Here, we show that FOXM1-overexpressing breast cancer cells display an apoptosis-resistant phenotype, which associates with the upregulation of expression of XIAP and Survivin antiapoptotic genes. Conversely, FOXM1 knockdown results in XIAP and Survivin downregulation as well as decreased binding of FOXM1 to the promoter regions of XIAP and Survivin. Consistently, FOXM1, XIAP, and Survivin expression levels were higher in taxane and anthracycline-resistant cell lines when compared to their sensitive counterparts and could not be downregulated in response to drug treatment. In agreement with our in vitro findings, we found that FOXM1 expression is significantly associated with Survivin and XIAP expression in samples from patients with IIIa stage breast invasive ductal carcinoma. Importantly, patients co-expressing FOXM1, Survivin, and nuclear XIAP had significantly worst overall survival, further confirming the physiological relevance of the regulation of Survivin and XIAP by FOXM1. Together, these findings suggest that the overexpression of FOXM1, XIAP, and Survivin contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients.}, } @article {pmid26401867, year = {2015}, author = {Barroso, U and Carvalho, MT and Veiga, ML and Moraes, MM and Cunha, CC and Lordêlo, P}, title = {Urodynamic outcome of parasacral transcutaneous electrical neural stimulation for overactive bladder in children.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {41}, number = {4}, pages = {739-743}, pmid = {26401867}, issn = {1677-6119}, mesh = {Child ; Compliance/physiology ; Female ; Humans ; *Lumbosacral Plexus ; Male ; Muscle Contraction/physiology ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder/physiopathology ; Urinary Bladder, Overactive/*therapy ; Urodynamics/*physiology ; }, abstract = {OBJECTIVE: To evaluate the urodynamic changes immediately after the first session (acute effect) and after the last session of parasacral TENS in children with idiopathic OAB.

MATERIALS AND METHODS: We performed urodynamic evaluation immediately before and after the first session of parasacral TENS and immediately after the last session (7 weeks later). Only children with idiopathic isolated OAB were included. Patients with dysfunctional voiding were not included.

RESULTS: 18 children (4 boys and 14 girls, mean age of 8.7) were included in the first analysis (urodynamic study before and immediately after the first session) and 12 agreed to undergo the third urodynamic study. Urodynamic before and immediately after the first session: There was no change in the urodynamic parameters, namely low MCC, low bladder compliance, presence of IDC, the average number of IDC, or in the maximum detrusor pressure after the first exam. Urodynamic after the last session: The bladder capacity improved in most patients with low capacity (58% vs. 8%). Detrusor overactivity was observed in 11 (92%) before treatment and 8 (76%) after. There was not a significant reduction in the average number of inhibited contractions after TENS (p=0.560) or in the detrusor pressure during the inhibited contraction (p=0.205).

CONCLUSION: There was no change in the urodynamic parameters immediately after the first session of stimulation. After the last session, the only urodynamic finding that showed improvement was bladder capacity.}, } @article {pmid26401837, year = {2015}, author = {Wolmer, L and Hamiel, D and Versano-Eisman, T and Slone, M and Margalit, N and Laor, N}, title = {Preschool Israeli Children Exposed to Rocket Attacks: Assessment, Risk, and Resilience.}, journal = {Journal of traumatic stress}, volume = {28}, number = {5}, pages = {441-447}, doi = {10.1002/jts.22040}, pmid = {26401837}, issn = {1573-6598}, mesh = {Child ; Child, Preschool ; Diagnostic and Statistical Manual of Mental Disorders ; Explosive Agents ; Female ; Humans ; Interviews as Topic ; Israel/epidemiology ; Life Change Events ; Male ; Mothers/*psychology ; Multivariate Analysis ; *Resilience, Psychological ; Stress Disorders, Post-Traumatic/diagnosis/etiology/*psychology ; Terrorism/*psychology ; }, abstract = {Preschool children are among the most vulnerable populations to adversity. This study described the effects of 4 weeks of daily exposure to rocket attacks on children living on Israel's southern border. Participants enrolled in this study were 122 preschool children (50% boys) between the ages 3 and 6 years from 10 kindergartens. We assessed mothers' report of children's symptoms according to the DSM-IV and alternative criteria resembling the DSM-5 criteria for posttraumatic stress disorder (PTSD), general adaptation, traumatic exposure, and stressful life events 3 months after the war. The prevalence of PTSD was lower when the diagnosis was derived from the DSM-IV (4%) than from the DSM-5 criteria (14%). Mothers of children with 4 or more stressful life events reported more functional impairment in social, occupational, and other important areas of functioning compared to children with 0 or 1 stressful life event. Children with more severe exposure showed more severe symptoms and mothers had more concerns about the child's functioning (η(p)(2) = .09-.25). Stressful life events and exposure to traumatic experiences accounted for 32% of the variance in PTSD and 19% of the variance in the adaptation scale. Results were explored in terms of risk and resilience factors.}, } @article {pmid26400100, year = {2015}, author = {Qin, F and Zhang, H and Ma, L and Liu, X and Dai, K and Li, W and Gu, F and Fu, L and Ma, Y}, title = {Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {14430}, pmid = {26400100}, issn = {2045-2322}, support = {R03 AA020101/AA/NIAAA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Brain Neoplasms/*metabolism/mortality/*secondary ; Breast Neoplasms/*metabolism/mortality/*pathology ; Carcinoma in Situ/genetics ; Carcinoma, Ductal, Breast/genetics/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Middle Aged ; Nerve Tissue Proteins/genetics/*metabolism ; Prognosis ; Proportional Hazards Models ; Receptors, Immunologic/genetics/*metabolism ; }, abstract = {Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.}, } @article {pmid26397772, year = {2015}, author = {Aguiar, FN and Cirqueira, CS and Bacchi, CE and Carvalho, FM}, title = {Morphologic, molecular and microenvironment factors associated with stromal invasion in breast ductal carcinoma in situ: Role of myoepithelial cells.}, journal = {Breast disease}, volume = {35}, number = {4}, pages = {249-252}, doi = {10.3233/BD-150416}, pmid = {26397772}, issn = {1558-1551}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Keratin-6/analysis ; Middle Aged ; Neoplasm Invasiveness ; Neprilysin/analysis ; Phenotype ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Smooth Muscle Myosins/analysis ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Ductal carcinoma in situ is the last step preceding invasive ductal carcinoma in breast carcinogenesis.

OBJECTIVE: We investigated the role of myoepithelial cells and epithelium characteristics as predictors of the risk of stromal invasion.

METHODS: We selected 236 cases with initial diagnosis of DCIS followed by surgical ressection distributed in groups 1 (without invasion) and 2 (with invasive carcinoma).

RESULTS: The risk of stromal invasion after a DCIS diagnosis in biopsy was associated to triple-negative profile and loss of CD10 expression by myoepithelial cells, and inversely associated with CK5/6 expression by neoplastic cells and high expression of Smooth Muscle Myosin Heavy Chain (SMMHC) by myoepithelial cells.

CONCLUSIONS: A combination of characteristics of epithelial and myoepithelial cells in DCIS in biopsy specimens is related to the risk of stromal invasion.}, } @article {pmid26396924, year = {2015}, author = {Usmani, A and Shoro, AA and Memon, Z and Hussain, M and Rehman, R}, title = {Diagnostic, prognostic and predictive value of MicroRNA-21 in breast cancer patients, their daughters and healthy individuals.}, journal = {American journal of cancer research}, volume = {5}, number = {8}, pages = {2484-2490}, pmid = {26396924}, issn = {2156-6976}, abstract = {MicroRNA-21 (miR-21) located on 17q23.1 expressed in breast cancer has anti-apoptotic ability and causes tumor cell growth. It is also involved in functions such as signal transduction pathways effecting normal cell growth and differentiation. The primary objective of the study was to identify presence of miR-21 in the serum levels of stage III invasive ductal carcinoma patients and compare its expression with age matched healthy individuals and daughters of index cases. The secondary objective was to evaluate the significance of serum miR-21 gene expression with histologically proven estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) proteins. A total of 132 subjects were recruited: 50 (cases) of stage III invasive ductal carcinoma patients who had not undergone any chemotherapy or surgery were randomly picked with exclusion of females with other types of breast carcinoma. Age-matched, 50 healthy individuals (control A) were selected by purposive sampling after confirmation of no palpable lump/s in their breasts together with 32 daughters of index cases (control B). Serum tests were run on Real Time quantitative Reverse Transcription PCR, threshold cycle was determined and fold change calculated.Normality of continuous variables was assessed by Shapiro-Wilk's test, groups compared by student t-test, Mann-Whitney test and Fisher exact test, P-value ≤ 0.05 was considered significant. We observed that miR-21 was significantly higher in cases as compared to control A and B (P = 0.001) however control B showed significant gene expression as compared to control A (P = 0.001). The cases were also divided as positive or negative for ER, PR and HER2. High expression of miR-21 in females with stage III invasive ductal carcinoma had been calculated as compared to its age matched healthy subjects. It was observed that triple negative cases showed a greater expression of gene as compared to other groups (P = 0.001). Expression of miR-21 in daughters of the cases was significantly higher as compared to healthy controls but lesser than females with invasive intraductal carcinoma. This result strengthens the concept of inheritability of disease with prediction of miR-21 as a potentially strong diagnostic and prognostic biomarker of breast cancer.}, } @article {pmid26394678, year = {2016}, author = {Tessitore, A and Giordano, A and Russo, A and Tedeschi, G}, title = {Structural connectivity in Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {22 Suppl 1}, number = {}, pages = {S56-9}, doi = {10.1016/j.parkreldis.2015.09.018}, pmid = {26394678}, issn = {1873-5126}, mesh = {Animals ; Brain/*metabolism/*pathology ; Diffusion Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging/methods ; Humans ; Magnetic Resonance Imaging/methods ; Nerve Net/*metabolism/*pathology ; Parkinson Disease/*diagnosis/*metabolism ; White Matter/metabolism/pathology ; }, abstract = {In the last decades a rapid evolution of structural advanced MRI techniques has occurred supporting the diagnosis of idiopathic Parkinson's disease, allowing us to further investigate the disease progression from nigral to extra-nigral degeneration and finally to detect pre-manifest Parkinson's disease. Diffusion-weighted imaging and diffusion tensor imaging represent advanced morphological approaches useful to detect changes in white matter integrity. These techniques, indeed, by measuring the translational displacement of water molecules in terms of fractional anisotropy and mean diffusivity, represent a powerful tool for the visualization of white matter changes, offering a unique window on brain structural connectivity. Microstructural changes can either be extracted locally in predefined regions using a region of interest analysis and tractography or, alternatively, globally into the brain using a voxel-based analysis or tract-based spatial statistics. The aim of this report was not only to summarize the distribution and nature of these alterations in Parkinson's disease but also to highlight the potential correlations between clinical, cognitive parameters and microstructural tissue loss.}, } @article {pmid26394603, year = {2015}, author = {Padovese, V and Racalbuto, V and Barnabas, GA and Morrone, A}, title = {Operational research on the correlation between skin diseases and HIV infection in Tigray region, Ethiopia.}, journal = {International journal of dermatology}, volume = {54}, number = {10}, pages = {1169-1174}, doi = {10.1111/ijd.12809}, pmid = {26394603}, issn = {1365-4632}, mesh = {Adult ; Candidiasis, Oral/epidemiology ; Case-Control Studies ; Condylomata Acuminata/epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; HIV Infections/diagnosis/*epidemiology ; Hair Diseases/epidemiology ; Herpes Zoster/epidemiology ; Humans ; Leukoplakia, Hairy/epidemiology ; Male ; Prevalence ; Prurigo/epidemiology ; Skin Diseases/*epidemiology ; Tongue Diseases/epidemiology ; }, abstract = {BACKGROUND: In Ethiopia, skin diseases are among the leading causes of outpatient attendance to primary health service. Correlation of skin diseases and HIV has long been recognized and used to guide medical management in resource-limited settings. Therefore, this study aims to assess the correlation of skin diseases and HIV infection, to estimate epidemiological distribution in the study area, and to provide health workers of skin indicators for HIV early detection.

METHODS: The operational research was designed as a case-control study and carried out in three intervention districts of Tigray region; baseline and final data on skin diseases and HIV were compared with those of three control districts matched for population size, density, and environmental characteristics. Health workers of intervention districts were trained on skin diseases/STIs diagnosis and treatment. Data were collected from study and control districts and then analyzed at the Italian Dermatological Centre (IDC) in Mekele.

RESULTS: In the research period, a total of 1044 HIV positive patients were detected. Disorders of skin and mucous membranes statistically related with HIV (P < 0.05) were tongue papillary atrophy (80%), oral hairy leukoplakia (69%), herpes zoster (66%), oral candidiasis (50%), pruritic papular eruption (43%), condylomata acuminata (38%), and telogen effluvium (27%).

CONCLUSIONS: The high frequency of oral disorders and telogen effluvium is not described in literature and may be indicative for case detection. Operational research offers significant gains on health service delivery and outcomes at relatively low cost and in a short timeframe.}, } @article {pmid26392358, year = {2015}, author = {Moelans, CB and Vlug, EJ and Ercan, C and Bult, P and Buerger, H and Cserni, G and van Diest, PJ and Derksen, PW}, title = {Methylation biomarkers for pleomorphic lobular breast cancer - a short report.}, journal = {Cellular oncology (Dordrecht)}, volume = {38}, number = {5}, pages = {397-405}, pmid = {26392358}, issn = {2211-3436}, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Analysis of Variance ; BRCA1 Protein/genetics ; Biomarkers, Tumor/classification/*genetics ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Carcinoma, Lobular/diagnosis/*genetics ; Cluster Analysis ; *DNA Methylation ; DNA-Binding Proteins/genetics ; Diagnosis, Differential ; Female ; Humans ; Logistic Models ; Multiplex Polymerase Chain Reaction/methods ; MutL Protein Homolog 1 ; Nuclear Proteins/genetics ; Promoter Regions, Genetic/genetics ; ROC Curve ; Tumor Protein p73 ; Tumor Suppressor Proteins/classification/genetics ; }, abstract = {BACKGROUND: Pleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.

METHODS: We performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.

RESULTS: We found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.

CONCLUSION: This is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.}, } @article {pmid26392199, year = {2015}, author = {Chen, HL and Ding, A}, title = {Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast.}, journal = {Breast (Edinburgh, Scotland)}, volume = {24}, number = {6}, pages = {723-731}, doi = {10.1016/j.breast.2015.09.001}, pmid = {26392199}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/*pathology ; Carcinoma, Papillary/chemistry/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/chemistry/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison.

PATIENTS AND METHODS: Retrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals.

RESULTS: For IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475).

CONCLUSIONS: IMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases.}, } @article {pmid26391857, year = {2015}, author = {Sumkin, JH and Ganott, MA and Chough, DM and Catullo, VJ and Zuley, ML and Shinde, DD and Hakim, CM and Bandos, AI and Gur, D}, title = {Recall Rate Reduction with Tomosynthesis During Baseline Screening Examinations: An Assessment From a Prospective Trial.}, journal = {Academic radiology}, volume = {22}, number = {12}, pages = {1477-1482}, pmid = {26391857}, issn = {1878-4046}, support = {R01 CA143019/CA/NCI NIH HHS/United States ; CA143019/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Appointments and Schedules ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging ; Early Detection of Cancer ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Pennsylvania ; Prospective Studies ; *Radiographic Image Interpretation, Computer-Assisted ; Tomography, X-Ray Computed/methods ; }, abstract = {RATIONALE AND OBJECTIVES: Assess results of a prospective, single-site clinical study evaluating digital breast tomosynthesis (DBT) during baseline screening mammography.

MATERIALS AND METHODS: Under an institutional review board-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, consenting women between ages 34 and 56 years scheduled for their initial and/or baseline screening mammogram underwent both full field digital mammography (FFDM) and DBT. The FFDM and the FFDM plus DBT images were interpreted independently in a reader by mode balanced approach by two of 14 participating radiologists. A woman was recalled for a diagnostic work-up if either radiologist recommended a recall. We report overall recall rates and related diagnostic outcome from the 1080 participants. Proportion of recommended recalls (Breast Imaging Reporting and Data System 0) were compared using a generalized linear mixed model (SAS 9.3) with a significance level of P = .0294.

RESULTS: The fraction of women without breast cancer recommended for recall using FFDM alone and FFDM plus DBT were 412 of 1074 (38.4%) and 274 of 1074 (25.5%), respectively (P < .001). Large inter-reader variability in terms of recall reduction was observed among the 14 readers; however, 11 of 14 readers recalled fewer women using FFDM plus DBT (5 with P < .015). Six cancers (four ductal carcinomas in situ [DCIS] and two invasive ductal carcinomas [IDC]) were detected. One IDC was detected only on DBT and one DCIS cancer was detected only on FFDM, whereas the remaining cancers were detected on both modalities.

CONCLUSIONS: The use of FFDM plus DBT resulted in a significant decrease in recall rates during baseline screening mammography with no reduction in sensitivity.}, } @article {pmid26384318, year = {2015}, author = {Elsarraj, HS and Hong, Y and Valdez, KE and Michaels, W and Hook, M and Smith, WP and Chien, J and Herschkowitz, JI and Troester, MA and Beck, M and Inciardi, M and Gatewood, J and May, L and Cusick, T and McGinness, M and Ricci, L and Fan, F and Tawfik, O and Marks, JR and Knapp, JR and Yeh, HW and Thomas, P and Carrasco, DR and Fields, TA and Godwin, AK and Behbod, F}, title = {Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {128}, pmid = {26384318}, issn = {1465-542X}, support = {R01 CA207445/CA/NCI NIH HHS/United States ; P20 RR016475/RR/NCRR NIH HHS/United States ; HD02528/HD/NICHD NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; R21 CA185460/CA/NCI NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; 1R21CA185460-01/CA/NCI NIH HHS/United States ; U01 CA084955/CA/NCI NIH HHS/United States ; U01CA113916/CA/NCI NIH HHS/United States ; U01 CA113916/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Female ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Proteins/*genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Transcription Factors ; Transcription, Genetic/genetics ; Transcriptome/*genetics ; Up-Regulation/genetics ; Wnt Proteins/genetics ; beta Catenin/genetics ; }, abstract = {INTRODUCTION: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized.

METHODS: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers.

RESULTS: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification.

CONCLUSION: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.}, } @article {pmid26381749, year = {2015}, author = {Roque, M and Duarte, I and Fouto, O and Távora, I}, title = {Invasive Ductal Carcinoma of the Breast in a Complex Cyst.}, journal = {The breast journal}, volume = {21}, number = {6}, pages = {683-684}, doi = {10.1111/tbj.12505}, pmid = {26381749}, issn = {1524-4741}, mesh = {Adult ; Breast Cyst/complications/*diagnosis ; Breast Neoplasms/complications/*diagnosis ; Carcinoma, Ductal, Breast/complications/*diagnosis ; Female ; Humans ; Mammography ; Ultrasonography, Mammary ; }, } @article {pmid26376021, year = {2015}, author = {Wong, SM and Freedman, RA and Sagara, Y and Stamell, EF and Desantis, SD and Barry, WT and Golshan, M}, title = {The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma.}, journal = {Cancer}, volume = {121}, number = {24}, pages = {4333-4340}, doi = {10.1002/cncr.29687}, pmid = {26376021}, issn = {1097-0142}, mesh = {Axilla ; Breast Neoplasms/complications/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Databases, Factual ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Paget's Disease, Mammary/complications/metabolism/*pathology/therapy ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; SEER Program ; Tumor Burden ; }, abstract = {BACKGROUND: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC).

METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression.

RESULTS: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD-IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P < .001), high grade (63.5% vs 40.3%; P < .001), >2 cm in greatest dimension (47.1% vs 35.7%; P < .001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P < .001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P < .001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P = .24).

CONCLUSIONS: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors.}, } @article {pmid26374642, year = {2016}, author = {Jiang, K and Gao, Y and Hou, W and Tian, F and Ying, W and Li, L and Bai, B and Hou, G and Wang, PG and Zhang, L}, title = {Proteomic analysis of O-GlcNAcylated proteins in invasive ductal breast carcinomas with and without lymph node metastasis.}, journal = {Amino acids}, volume = {48}, number = {2}, pages = {365-374}, doi = {10.1007/s00726-015-2089-8}, pmid = {26374642}, issn = {1438-2199}, mesh = {Acetylglucosamine/*metabolism ; Carcinoma, Ductal, Breast/*pathology ; Chromatography, Liquid ; Female ; Glycosylation ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; N-Acetylglucosaminyltransferases/*metabolism ; Protein Processing, Post-Translational ; Proteomics ; Tandem Mass Spectrometry ; }, abstract = {The potential role of protein O-GlcNAcylation in cancer has been studied extensively, and the spread of cancer cells to regional lymph nodes is the first step in the dissemination of breast cancer. However, the correlation between O-GlcNAcylation and lymphatic metastasis in breast cancer remains elusive. In this study, we demonstrated that the overall O-GlcNAcylation as well as O-GlcNAc transferase (OGT) tends to decrease in response to the augmentation of lymph node metastasis (LNM) in invasive ductal breast carcinomas (IDCs). Although accumulating evidence indicates that individual O-GlcNAcylation may be important in the pathogenesis of breast cancer, O-GlcNAcylated proteins in IDCs are still largely unexplored. Herein, O-GlcNAcylated proteins of IDCs were chemo-enzymatically enriched and identified via liquid chromatography combined with tandem mass spectrometry. In total, 155 O-GlcNAcylated proteins were determined, of which 41 were only observed in LNM tissues, while 40 were unique in non-LNM samples. Gene ontology analysis showed that O-GlcNAc is primarily a nucleocytoplasmic post-translational modification, and most enriched functional terms were related to cancer development in both metastatic and non-metastatic IDCs. Moreover, several O-GlcNAcylated proteins involved in glycolysis and its accessory pathway were identified from LNM and non-LNM groups, respectively. These results indicate that the O-GlcNAcylation statuses of individual proteins were independent of the overall O-GlcNAcylation levels of metastatic and non-metastatic IDCs. Aberrant O-GlcNAc modification of these proteins might be associated with LNM progression.}, } @article {pmid26374568, year = {2015}, author = {Corathers, SD and Schoettker, PJ and Clements, MA and List, BA and Mullen, D and Ohmer, A and Shah, A and Lee, J}, title = {Health-system-based interventions to improve care in pediatric and adolescent type 1 diabetes.}, journal = {Current diabetes reports}, volume = {15}, number = {11}, pages = {91}, pmid = {26374568}, issn = {1539-0829}, mesh = {Adolescent ; Blood Glucose/analysis ; Child ; Diabetes Mellitus, Type 1/diagnosis/*therapy ; Humans ; Patient Education as Topic ; Quality Improvement ; Self Care ; Treatment Outcome ; }, abstract = {Despite significant advances in pharmacology and technology, glycemic targets are difficult to achieve for patients with type 1 diabetes (T1D) and management remains burdensome for patients and their families. Quality improvement (QI) science offers a methodology to identify an aim, evaluate complex contributors to the goal, and test potential interventions to achieve outcomes of interest. Day-to-day management of diabetes is often an iterative process but interventions exist at all care levels: individual patient and family, clinic, and larger population and health system. This article reviews current literature and proposes novel QI interventions for enhancing health outcomes, with attention to essential determinants or drivers of improved glycemic control and patient experience for pediatric T1D in the context of the Chronic Care Model. In-depth consideration of key drivers of successful T1D care, including self-management and integration of technology, are explored, and examples of larger health systems with improved outcomes, including Learning Health Systems are highlighted.}, } @article {pmid26374470, year = {2015}, author = {Bitencourt, AG and Pereira, NP and França, LK and Silva, CB and Paludo, J and Paiva, HL and Graziano, L and Guatelli, CS and Souza, JA and Marques, EF}, title = {Role of MRI in the staging of breast cancer patients: does histological type and molecular subtype matter?.}, journal = {The British journal of radiology}, volume = {88}, number = {1055}, pages = {20150458}, pmid = {26374470}, issn = {1748-880X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Staging ; Preoperative Period ; Retrospective Studies ; }, abstract = {OBJECTIVE: To assess the role of MRI in the pre-operative staging of patients with different histological types and molecular subtypes of breast cancer, by the assessment of the dimensions of the main tumour and identification of multifocal and/or multicentric disease.

METHODS: The study included 160 females diagnosed with breast cancer who underwent breast MRI for pre-operative staging. The size of the primary tumour evaluated by MRI was compared with the pathology (gold standard) using the Pearson's correlation coefficient (r). The presence of multifocal and/or multicentric disease was also evaluated.

RESULTS: The mean age of patients was 52.6 years (range 30-81 years). Correlation between the largest dimension of the main tumour measured by MRI and pathology was worse for non-special type/invasive ductal carcinoma than for other histological types and was better for luminal A and triple-negative than for luminal B and Her-2 molecular subtypes. Multifocal and/or multicentric disease was present in 48 patients (30.0%), and it was more common in breast carcinomas classified as Her-2 molecular subtype. There was no statistically significant difference in the frequency of multifocal and/or multicentric tumours identified only by MRI in relation to histological type or molecular subtype.

CONCLUSION: The results of this retrospective study demonstrated that histological types and molecular subtypes might influence the MRI assessment of breast cancers, especially in the evaluation of tumour size.

ADVANCES IN KNOWLEDGE: The real benefit of MRI for treatment planning in patients with breast cancer may be different according to the histological type and molecular subtype.}, } @article {pmid26373617, year = {2016}, author = {Zheng, B and Ohuchida, K and Chijiiwa, Y and Zhao, M and Mizuuchi, Y and Cui, L and Horioka, K and Ohtsuka, T and Mizumoto, K and Oda, Y and Hashizume, M and Nakamura, M and Tanaka, M}, title = {CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression.}, journal = {Molecular carcinogenesis}, volume = {55}, number = {11}, pages = {1560-1572}, doi = {10.1002/mc.22409}, pmid = {26373617}, issn = {1098-2744}, mesh = {CD146 Antigen/genetics/metabolism ; Cancer-Associated Fibroblasts/cytology/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Disease Progression ; *Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high-grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-κB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression. © 2015 Wiley Periodicals, Inc.}, } @article {pmid26367733, year = {2015}, author = {Simsek, BC and Turk, BA and Ozen, F and Tuzcu, M and Kanter, M}, title = {Investigation of telomerase activity and apoptosis on invasive ductal carcinoma of the breast using immunohistochemical and Western blot methods.}, journal = {European review for medical and pharmacological sciences}, volume = {19}, number = {16}, pages = {3089-3099}, pmid = {26367733}, issn = {2284-0729}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis/physiology ; Blotting, Western/*methods ; Breast Neoplasms/*enzymology/*pathology ; Carcinoma, Ductal, Breast/*enzymology/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Telomerase/*metabolism ; }, abstract = {OBJECTIVE: Invasive ductal carcinoma (IDC) comprises the largest group of breast cancers. This study aimed to investigate telomerase activity and apoptosis using immunohistochemical and Western blot methods.

PATIENTS AND METHODS: In total, 75 cases that had been diagnosed as IDC and 20 cases that had undergone a freezing procedure were included. The histological sections were stained with Bax, Bcl-2, hTERT and BNIP3. The ages of the patients, as well as their hormonal status and tumour sizes and grades were evaluated, as well as the staining characteristics of the antibodies in question.

RESULTS: A decrease in Bcl-2 positivity and an increase in Bax positivity were found immunohistochemically with increasing tumour grades. The data obtained by western blot method showed that Bcl-2 was highest in grade 1 tumours although these results were not statistically significant. The relationship between estrogen and progesterone receptor positivity and Bcl-2 was statistically significant, suggesting there is hormonal control through apoptosis. BNIP3 was found to be decreased with increasing tumour grades. Similarly, BNIP3 was found to be having the lowest value in grade 3 tumours by western blot method. Furthermore, hTERT was found to be increased with increasing tumour grades. In the western blot method, hTERT increased nearly four-fold compared to the control. In addition, hTERT, which was seen in very high levels in tumours, may be a helpful cancer marker. Both hTERT and BNIP3 are important markers that can provide information about prognosis.

CONCLUSIONS: Big improvements can be achieved in tumour progression control with new treatment modalities that stop telomerase activity and hypoxic cell death.}, } @article {pmid26359561, year = {2016}, author = {Makis, W and Robinson, D and McEwan, AJ and Riauka, TA}, title = {Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.}, journal = {Clinical nuclear medicine}, volume = {41}, number = {4}, pages = {319-320}, doi = {10.1097/RLU.0000000000000967}, pmid = {26359561}, issn = {1536-0229}, mesh = {Antimony/administration & dosage/*adverse effects ; Artifacts ; Breast Neoplasms/*diagnostic imaging ; Female ; Humans ; Lymph Nodes/*diagnostic imaging ; Middle Aged ; Radiopharmaceuticals/administration & dosage/*adverse effects ; Technetium Compounds/administration & dosage/*adverse effects ; }, abstract = {A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 μSv).}, } @article {pmid26358931, year = {2015}, author = {Abrahão, Kde S and Bergmann, A and Aguiar, SS and Thuler, LC}, title = {Determinants of advanced stage presentation of breast cancer in 87,969 Brazilian women.}, journal = {Maturitas}, volume = {82}, number = {4}, pages = {365-370}, doi = {10.1016/j.maturitas.2015.07.021}, pmid = {26358931}, issn = {1873-4111}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brazil ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Cross-Sectional Studies ; Educational Status ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Patient Acceptance of Health Care/*statistics & numerical data ; Residence Characteristics ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is commonly diagnosed at an advanced stage in Brazil.

AIM: Analyze the determinants of advanced staging in Brazilian women with breast cancer.

METHODS: Crosssectional study, including women diagnosed with breast cancer in Brazil, between 2000 and 2009.

RESULTS: A total of 59,317 women were included, 53.5% being classified as advanced stage (≥IIB). Younger age (18 to 49 years old) (OR=1.61 95% CI 1.51 to 1.72) or between 40 and 49 years old (OR=1.08 95% CI 1.03 to 1.14), having low educational level (OR=1.53 95% CI 1.48 to 1.58), living in less developed geographical regions (OR=1.27 95% CI 1.21 to 1.33), having invasive ductal carcinoma (OR=2.70 95% CI 2.56 to 2.84) and invasive lobular carcinoma (OR=2.63 95% CI 2.42 to 2.86) were associated with advanced breast cancer.

CONCLUSION: We conclude that future interventions should focus on these high risk groups.}, } @article {pmid26358820, year = {2015}, author = {Wu, Y and Fu, F and Lian, Y and Nie, Y and Zhuo, S and Wang, C and Chen, J}, title = {Monitoring the progression from intraductal carcinoma to invasive ductal carcinoma based on multiphoton microscopy.}, journal = {Journal of biomedical optics}, volume = {20}, number = {9}, pages = {096007}, doi = {10.1117/1.JBO.20.9.096007}, pmid = {26358820}, issn = {1560-2281}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Disease Progression ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Microscopy, Fluorescence, Multiphoton/*methods ; Middle Aged ; }, abstract = {Intraductal carcinoma is a precancerous lesion of the breast and the immediate precursor of invasive ductal carcinoma. Multiphoton microscopy (MPM) was used to monitor the progression from intraductal carcinoma to invasive ductal carcinoma, which can improve early detection of precursor lesions and halt progression to invasive neoplastic disease. It was found that MPM has the capability to reveal the qualitative changes in features of cells, structure of basement membranes, and architecture of collagens during the development from intraductal carcinoma to invasive ductal carcinoma, as well as the quantitative alterations in nuclear area, circle length of basement membrane, and collagen density. Combined with intra-fiberoptic ductoscopy or transdermal biopsy needle, MPM has the potential to provide immediate histological diagnosis of tumor progression in the field of breast carcinoma.}, } @article {pmid26358115, year = {2016}, author = {Chikman, B and Davidson, T and Kais, H and Jeroukhimov, I and Leshno, A and Sandbank, J and Halevy, A and Lavy, R}, title = {Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?.}, journal = {Familial cancer}, volume = {15}, number = {1}, pages = {41-47}, pmid = {26358115}, issn = {1573-7292}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/genetics ; Carcinoma, Ductal, Breast/epidemiology/genetics ; Carcinoma, Lobular/*epidemiology/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Humans ; Incidence ; Middle Aged ; Pedigree ; Retrospective Studies ; Stomach Neoplasms/*epidemiology/genetics ; }, abstract = {CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and ≥50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.}, } @article {pmid26357495, year = {2015}, author = {Seo, KJ and An, YY and Whang, IY and Chang, ED and Kang, BJ and Kim, SH and Park, CS and Kim, JS and Hong, H}, title = {Sonography of Invasive Apocrine Carcinoma of the Breast in Five Cases.}, journal = {Korean journal of radiology}, volume = {16}, number = {5}, pages = {1006-1011}, pmid = {26357495}, issn = {2005-8330}, mesh = {Aged ; Apocrine Glands/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Carcinoma/*diagnosis/diagnostic imaging/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Positron-Emission Tomography ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tomography, X-Ray Computed ; Tumor Suppressor Protein p53/metabolism ; Ultrasonography ; }, abstract = {OBJECTIVE: To evaluate the sonographic features of invasive apocrine carcinoma (IAC) of the breast.

MATERIALS AND METHODS: This study included five pathologically proven cases of IAC, and their sonographic features were retrospectively analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon.

RESULTS: All five lesions involved the left breast and were seen as irregularly shaped masses. All lesions, except one, had a parallel orientation to the chest wall. All five lesions showed noncircumscribed margins and heterogeneous echotexture; however, they showed various posterior features. One lesion had edema as an associated feature. Sonographic assessments were classified as BI-RADS category 4 in all five cases.

CONCLUSION: Invasive apocrine carcinoma sonographic findings are difficult to differentiate from those of invasive ductal carcinoma of no special type.}, } @article {pmid26357489, year = {2015}, author = {Kiba, T and Morii, N and Takahashi, H and Ozaki, S and Atsumi, M and Masumoto, F and Yamashiro, H}, title = {Pathological response rate in hormone-positive breast cancer patients treated with neoadjuvant FEC and triweekly docetaxel: a case series.}, journal = {Breast cancer (Dove Medical Press)}, volume = {7}, number = {}, pages = {245-250}, pmid = {26357489}, issn = {1179-1314}, abstract = {We recently reported that neoadjuvant 5-FU, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel and/or trastuzumab induced a high pathological complete response (pCR) rate in hormone-negative patients. The present study examined the therapeutic efficacy of neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab in the treatment of hormone-positive patients. Between February 2012 and December 2013, 16 hormone-positive patients with local breast cancer (luminal A type: six patients; luminal B type: two patients; luminal HER2 type: eight patients) were included in the study. The histological type of the primary cancer was invasive ductal carcinoma in all patients. The cancer stages in the 16 women who received this regimen were stage I in five (31.3%), IIA in four (25.0%), IIB in five (31.3%), IIIB in one (6.3%), and IIIC in one (6.3%). Regarding clinical TNM classification, five patients were T1N0M0, one was T1N1M0, three were T2N0M0, five were T2N1M0, one was T3N2M0, and one was T4N0M0. The pCR was evaluated using resected tissue after neoadjuvant chemotherapy according to the evaluation criteria of the Japanese Breast Cancer Society. Patients were classified into pathologic responders (grade 2: 50.0% of all patients: 2/6 of luminal A type; 6/8 of Luminal HER2 type) and nonresponders (grades 0 and 1: 50.0% of all patients: 4/6 of luminal A type; 2/2 of luminal B type; 2/8 of luminal HER2 type) according to the grade of the tumor. The pCR rate was 0%. Hematologic and nonhematologic toxicity was reversible and manageable. This study demonstrated that neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab did induce a high pathologic response in luminal HER2 type, but not in luminal A and B types, and did not induce a high pCR rate in the hormone-positive patients.}, } @article {pmid26353854, year = {2016}, author = {Himuro, T and Horimoto, Y and Arakawa, A and Tanabe, M and Saito, M}, title = {Ki67 Heterogeneity in Estrogen Receptor-Positive Breast Cancers: Which Tumor Type Has the Most Heterogeneity?.}, journal = {International journal of surgical pathology}, volume = {24}, number = {2}, pages = {103-107}, doi = {10.1177/1066896915605179}, pmid = {26353854}, issn = {1940-2465}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Receptors, Estrogen/*metabolism ; }, abstract = {Heterogeneity of Ki67 expression, often seen in breast cancer, can make evaluation of the expression of this marker difficult and give rise to confusion when considering adjuvant treatments for patients. Herein, we investigated estrogen receptor-positive breast cancers to reveal the tumor characteristics associated with Ki67 heterogeneity. Surgical specimens from 85 invasive ductal carcinomas of no special type and 13 invasive lobular carcinomas were examined. We first calculated the differences between Ki67 expression in a hot spot and those in 4 random fields on the same slide. We then evaluated Ki67 heterogeneity within the tumor, based on these differences. Among clinicopathological factors, solid-tubular carcinoma, an architectural growth pattern subtype of invasive ductal carcinoma, correlated with high Ki67 heterogeneity (P < .05). Our results indicate that we might need to be aware of histological patterns when selecting appropriate microscopic fields for evaluating Ki67 expression.}, } @article {pmid26353381, year = {2016}, author = {Catanzaro, D and Shackney, SE and Schaffer, AA and Schwartz, R}, title = {Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {13}, number = {4}, pages = {643-655}, pmid = {26353381}, issn = {1557-9964}, support = {R01 AI076318/AI/NIAID NIH HHS/United States ; R01 CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Breast Neoplasms/diagnosis/*genetics/*physiopathology ; Carcinoma, Ductal/diagnosis/*genetics/*physiopathology ; Clonal Evolution ; Cluster Analysis ; Computational Biology/*methods ; Female ; Humans ; Models, Genetic ; }, abstract = {Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.}, } @article {pmid26351488, year = {2015}, author = {Siadati, S and Sharbatdaran, M and Nikbakhsh, N and Ghaemian, N}, title = {Correlation of ER, PR and HER-2/Neu with other Prognostic Factors in Infiltrating Ductal Carcinoma of Breast.}, journal = {Iranian journal of pathology}, volume = {10}, number = {3}, pages = {221-226}, pmid = {26351488}, issn = {1735-5303}, abstract = {BACKGROUND AND OBJECTIVES: Breast cancer is the most common malignancy among women in the world. The aim of this study was to assess estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu of infiltrating ductal carcinoma (IDC) with tumor size, histologic grade, lymph node metastasis and age.

METHODS: This study was carried out on 300 tissue blocks of patients with IDC who underwent mastectomy from 2007 to 2011 in Shahid Beheshti Hospital, affiliated to Babol University of Medical Sciences, Babol, Iran. Data including age, tumor size, and histologic grade and lymph node status retrieved from pathology department.

RESULT: The mean age of the patients was 40.2±2.3 (ranged 19-82 years). ER and PR were positively correlated with each other (P = 0.001) and they inversely correlated with HER-2/neu (P =0.001). We observed correlation between ER and PR expression and low histologic grade (P = 0.001) and HER-2/neu expression and high histologic grade (P = 0.003). There was correlation between HER-2/neu expression and lymph node involvement (P =0.03). None of these makers showed correlation with age and tumor size (P > 0.05).

CONCLUSION: Our findings indicate the importance of ER, PR and HER-2/neu expression as prognostic factors for therapeutic decision.}, } @article {pmid26349603, year = {2015}, author = {Omran, OM and Al Sheeha, M}, title = {Cytoskeletal Focal Adhesion Proteins Fascin-1 and Paxillin Are Predictors of Malignant Progression and Poor Prognosis in Human Breast Cancer.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {34}, number = {3}, pages = {201-212}, doi = {10.1615/jenvironpatholtoxicoloncol.2015013663}, pmid = {26349603}, issn = {2162-6537}, mesh = {Adult ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/*genetics/pathology ; Carrier Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microfilament Proteins/*genetics/metabolism ; Middle Aged ; Paxillin/*genetics/metabolism ; Prognosis ; }, abstract = {Breast cancer is a major health problem in both developing and developed countries. The incremental motility of malignant cells is a critical step in their migration, invasion, and metastasis and is regulated by the reorganization of the actin cytoskeleton and regulation of focal adhesion. Fascin-1 and paxillin are essential components of these cellular structures. In cancer, the expression level of fascin-1 and paxillin can vary depending on cell type. However, its precise role in breast cancer of Saudi women has not been evaluated in any published study. We investigated fascin-1 and paxillin expression in breast carcinoma, and we have related these results to the established prognostic factors. We studied 100 breast carcinoma specimens. Immunohistochemical analyses for fascin-1 and paxillin were conducted on paraffin sections of breast tissues using the avidin-biotin peroxidase method. Fascin-1 and paxillin were expressed in 58% and 43% of infiltrating duct carcinoma (IDC) cases. There was a statistically significant correlation between fascin-1 and paxillin expression with each of the following: tumor grade, clinical stage, lymph-node metastasis grade, and HER2 expression. Furthermore, there was a significant correlation between fascin-1 expression with paxillin immunostaining but no such association with PR or ER status. Increased fascin-1 and paxillin expression in IDC cells and their correlation with poor prognostic factors support their strong correlation with tumor progression, invasion, and metastasis in human breast cancer, indicating that these markers can be used as a target for the development of novel therapies.}, } @article {pmid26347713, year = {2015}, author = {Bayindir, I and Babaeikelishomi, R and Kocanova, S and Sousa, IS and Lerch, S and Hardt, O and Wild, S and Bosio, A and Bystricky, K and Herzig, S and Vegiopoulos, A}, title = {Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning.}, journal = {Frontiers in endocrinology}, volume = {6}, number = {}, pages = {129}, pmid = {26347713}, issn = {1664-2392}, abstract = {De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.}, } @article {pmid26347357, year = {2015}, author = {Harrison, K and Hoad, G and Scott, P and Simpson, L and Horgan, GW and Smyth, E and Heys, SD and Haggarty, P}, title = {Breast cancer risk and imprinting methylation in blood.}, journal = {Clinical epigenetics}, volume = {7}, number = {1}, pages = {92}, pmid = {26347357}, issn = {1868-7075}, abstract = {BACKGROUND: Altered DNA methylation of imprinted genes has been implicated in a range of cancers. Imprinting is established early in development, and some are maintained throughout the life course in multiple tissues, providing a plausible mechanism linking known early life factors to cancer risk. This study investigated methylation status of seven imprinted differentially methylated regions-PLAGL1/ZAC1, H19-ICR1, IGF2-DMR2, KvDMR-ICR2, RB1, SNRPN-DMR1 and PEG3-in blood samples from 189 women with the most common type of invasive breast cancer (invasive ductal carcinoma-IDC), 41 women with in situ breast cancer (ductal carcinoma in situ-DCIS) and 363 matched disease-free controls.

RESULTS: There was no evidence that imprinted gene methylation levels varied with age (between 25 and 87 years old), weight or height. Higher PEG3 methylation was associated with an elevated risk of IDC (odds ratio (OR) 1.065; 95 % confidence interval (CI) 1.002, 1.132; p = 0.042) and DCIS (OR 1.139; 95 % CI 1.027, 1.263; p = 0.013). The effect was stronger when in situ and invasive breast cancer were combined (OR 1.079; 95 % CI 1.020, 1.142; p = 0.008). DCIS breast cancer risk increased with higher KvDMR-ICR2 methylation (OR 1.395; 95 % CI 1.190, 1.635; p < 0.001) and lower PLAGL1/ZAC1 methylation (OR 0.905; 95 % CI 0.833, 0.982; p = 0.017). In a combined model, only KvDMR-ICR2 methylation remained significantly associated.

CONCLUSIONS: These findings may help to improve our understanding of the aetiology of breast cancer and the importance of early life factors in particular. Imprinting methylation status also has the potential to contribute to the development of improved screening and treatment strategies for women with, or at risk of, breast cancer.}, } @article {pmid26336132, year = {2015}, author = {Döppler, H and Bastea, L and Borges, S and Geiger, X and Storz, P}, title = {The phosphorylation status of VASP at serine 322 can be predictive for aggressiveness of invasive ductal carcinoma.}, journal = {Oncotarget}, volume = {6}, number = {30}, pages = {29740-29752}, pmid = {26336132}, issn = {1949-2553}, support = {P50 CA116201/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; CA116201-03DR4/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal/genetics/*metabolism/pathology ; Cell Adhesion Molecules/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Cell Movement/genetics ; Disease Progression ; HeLa Cells ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; Microfilament Proteins/genetics/*metabolism ; Microscopy, Confocal ; Mutation ; Neoplasm Invasiveness ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Prognosis ; Protein Kinase D2 ; Protein Kinases/genetics/metabolism ; Serine/genetics/*metabolism ; Tissue Array Analysis ; }, abstract = {Vasodilator-stimulated phosphoprotein (VASP) signaling is critical for dynamic actin reorganization processes that define the motile phenotype of cells. Here we show that VASP is generally highly expressed in normal breast tissue and breast cancer. We also show that the phosphorylation status of VASP at S322 can be predictive for breast cancer progression to an aggressive phenotype. Our data indicate that phosphorylation at S322 is gradually decreased from normal breast to DCIS, luminal/ER+, HER2+ and basal-like/TN phenotypes. Similarly, the expression levels of PKD2, the kinase that phosphorylates VASP at this site, are decreased in invasive ductal carcinoma samples of all three groups. Overall, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.}, } @article {pmid26331372, year = {2016}, author = {Haffner, MC and Weier, C and Xu, MM and Vaghasia, A and Gürel, B and Gümüşkaya, B and Esopi, DM and Fedor, H and Tan, HL and Kulac, I and Hicks, J and Isaacs, WB and Lotan, TL and Nelson, WG and Yegnasubramanian, S and De Marzo, AM}, title = {Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.}, journal = {The Journal of pathology}, volume = {238}, number = {1}, pages = {31-41}, pmid = {26331372}, issn = {1096-9896}, support = {P50 CA058236/CA/NCI NIH HHS/United States ; R01 CA183965/CA/NCI NIH HHS/United States ; P30CA006973/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R01CA183965/CA/NCI NIH HHS/United States ; R01 CA070196/CA/NCI NIH HHS/United States ; P50CA58236/CA/NCI NIH HHS/United States ; P50CA058236/CA/NCI NIH HHS/United States ; R01CA070196/CA/NCI NIH HHS/United States ; T32 GM008752/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Cell Line, Tumor ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasm Invasiveness ; Oncogene Proteins, Fusion/genetics ; PTEN Phosphohydrolase/genetics ; Prostatic Intraepithelial Neoplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Trans-Activators/genetics ; Transcriptional Regulator ERG ; }, abstract = {Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification.}, } @article {pmid26329944, year = {2015}, author = {Islam, A and Khondker, NS and Rahman, S and Reza, E and Mahamud, MM and Shaon, SA and Mariam, L and Pathan, FH}, title = {A Comparative Study between FNAC and Histopathology in Diagnosis of Breast Lump.}, journal = {Mymensingh medical journal : MMJ}, volume = {24}, number = {3}, pages = {486-491}, pmid = {26329944}, issn = {1022-4742}, mesh = {Adult ; Bangladesh ; *Biopsy, Fine-Needle ; Breast/*pathology ; Breast Diseases/diagnosis/pathology ; Breast Neoplasms/*diagnosis/pathology ; Female ; Humans ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Worldwide a large number of patients have been suffering from breast lump and this trend is gradually increasing. It is difficult to determine whether a lump is benign or malignant from clinical assessment. Thus the need for microscopic tissue analysis arises. This study was designed to determine the value of fine needle aspiration cytology in the diagnosis of breast lumps and to compare the result of FNAC with histopathological diagnosis to assess its accuracy. A prospective study in the period of January 2009 to December 2010 was done. One hundred and ten (110) patients who came to the Department of Surgery in Mymensingh Medical College Hospital, Bangladesh in two years for their palpable breast masses were chosen for the study. There were 70(63.63%) benign, 33(30.00%) malignant and 07(6.36%) suspicious smears in FNAC. Inadequate samples were repeated. The number of repeats increased the diagnostic accuracy of aspirates which is statistically significant when compared with histopathology. In histopathology Invasive ductal carcinoma was the most commonly reported lesion with maximum incidence in the 4th, 5th, and 6th decades followed by invasive lobular carcinoma and other malignant lesions. FNAC serves as a rapid, economical and reliable tool for the diagnosis of palpable breast lesions and its reliability is influenced by the skillness of the aspirator. So physician should use this tool with clinical experience.}, } @article {pmid26329827, year = {2015}, author = {Webster, BL and Rabone, M and Pennance, T and Emery, AM and Allan, F and Gouvras, A and Knopp, S and Garba, A and Hamidou, AA and Mohammed, KA and Ame, SM and Rollinson, D and Webster, JP}, title = {Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.}, journal = {Parasites & vectors}, volume = {8}, number = {}, pages = {432}, pmid = {26329827}, issn = {1756-3305}, support = {104958/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cost-Benefit Analysis ; *Genetic Variation ; Genetics, Population ; Humans ; Larva/classification/genetics ; *Microsatellite Repeats ; Multiplex Polymerase Chain Reaction/*methods ; Niger ; Schistosoma haematobium/*classification/*genetics/isolation & purification ; Schistosomiasis haematobia/parasitology ; Tanzania ; Time Factors ; Urinary Tract Infections/parasitology ; }, abstract = {BACKGROUND: Human urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly targeted for control and regional elimination. The development of new high-throughput, cost-effective molecular tools and approaches are needed to monitor and evaluate the impact of control programs on the parasite populations. Microsatellite loci are genetic markers that can be used to investigate how parasite populations change over time and in relation to external influences such as control interventions.

FINDINGS: Here, 18 existing S. haematobium microsatellite loci were optimised to enable simultaneous amplification across two novel multiplex microsatellite PCR's, each containing nine loci. Methods were developed for the cost effective and rapid processing and microsatellite analysis of S. haematobium larval stages stored on Whatman-FTA cards and proved robust on miracidia and cercariae collected from Zanzibar and Niger.

CONCLUSION: The development of these novel and robust multiplex microsatellite assays, in combination with an improved protocol to elute gDNA from Whatman-FTA fixed schistosome larval stages, enables the high-throughput population genetic analysis of S. haematobium. The molecular resources and protocols described here advance the way researchers can perform multi locus-based population genetic analyses of S. haematobium as part of the evaluation and monitoring of schistosomiasis control programmes.}, } @article {pmid26329496, year = {2018}, author = {Chiacchio, S and Evangelista, L and Alsharif, A and Manca, G and DI Martino, F and Negri, A and Tredici, M and Cervino, AR and Puccini, G and Filidei, E and Ghilli, M and Naccarato, AG and Roncella, M and Volterrani, D}, title = {Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.}, journal = {The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...}, volume = {62}, number = {1}, pages = {101-111}, doi = {10.23736/S1824-4785.17.02810-2}, pmid = {26329496}, issn = {1827-1936}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Retrospective Studies ; }, abstract = {BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated.

METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity.

RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated.

CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.}, } @article {pmid26329135, year = {2016}, author = {Zhang, Z and Atwell, LL and Farris, PE and Ho, E and Shannon, J}, title = {Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies.}, journal = {Public health nutrition}, volume = {19}, number = {7}, pages = {1288-1295}, pmid = {26329135}, issn = {1475-2727}, support = {P01 CA090890/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; UL1TR000128/TR/NCATS NIH HHS/United States ; R21 CA132236/CA/NCI NIH HHS/United States ; R21 CA132236-01A2/CA/NCI NIH HHS/United States ; P30 ES000210/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers/blood/urine ; Biopsy ; Body Mass Index ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/genetics ; Cell Proliferation/physiology ; Creatinine/urine ; *Diet ; Double-Blind Method ; Female ; Histone Deacetylases/metabolism ; Humans ; Isothiocyanates/blood/urine ; Ki-67 Antigen/genetics/metabolism ; Life Style ; Linear Models ; Middle Aged ; Multivariate Analysis ; Nutrition Assessment ; Socioeconomic Factors ; Sulfoxides ; *Vegetables ; }, abstract = {OBJECTIVE: To examine the relationship between dietary cruciferous vegetable intake and selected tumour biomarkers for histone acetylation (H3K9ac, H3K18ac, HDAC3 and HDAC6), proliferation (Ki-67) and cell-cycle regulation (p21) from breast tissue.

DESIGN: The study used baseline data of women recruited to participate in a clinical trial of sulforaphane supplement. Dietary cruciferous vegetable intake was collected through a validated Arizona Cruciferous Vegetable Intake Questionnaire. Breast tissue was obtained from biopsy samples. Spearman correlations were calculated between intake of specific cruciferous vegetables and biomarkers. Tissue biomarkers were log2-transformed to obtain approximate normality. Linear regression analyses were conducted to examine associations between cruciferous vegetable intake and biomarkers adjusting for age and use of non-steroidal anti-inflammatory drugs. False discovery rate (FDR) was used to account for multiple comparisons.

SETTING: Clinical trial baseline.

SUBJECTS: Fifty-four women who had abnormal mammogram findings and were scheduled for breast biopsy.

RESULTS: Mean intake of total cruciferous vegetables from all food sources was 81·7 (sd 57·3) g/d. Mean urinary total sulforaphane metabolites was 0·08 (sd 0·07) µm/mm creatinine. Total cruciferous vegetable intake was inversely associated with Ki-67 protein expression in breast ductal carcinoma in situ (DCIS) tissue (β=-0·004; se=0·001; FDR q value=0·03), but not in benign or invasive ductal carcinoma (IDC) tissue. No association was found for other biomarkers measured (HDAC3, HDAC6, H3K9, H3K18 and p21) in all tissues examined (benign, DCIS and IDC).

CONCLUSIONS: The present study sought to provide additional evidence for the potential role of sulforaphane in histone acetylation and cell proliferation. Here, we report that total cruciferous vegetable intake is associated with decreased cell proliferation in breast DCIS tissue.}, } @article {pmid26328493, year = {2015}, author = {Kondo, N and Temma, T and Shimizu, Y and Ono, M and Saji, H}, title = {Radioiodinated Peptidic Imaging Probes for in Vivo Detection of Membrane Type-1 Matrix Metalloproteinase in Cancers.}, journal = {Biological & pharmaceutical bulletin}, volume = {38}, number = {9}, pages = {1375-1382}, doi = {10.1248/bpb.b15-00314}, pmid = {26328493}, issn = {1347-5215}, mesh = {Animals ; Biomarkers, Tumor/*metabolism ; Cell Line, Tumor ; Diagnostic Imaging ; Female ; Humans ; Iodine Radioisotopes ; Male ; Matrix Metalloproteinase 14/*metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasms/*metabolism ; Peptides/blood/pharmacokinetics/*pharmacology ; Plasma/chemistry ; }, abstract = {Membrane type-1 matrix metalloproteinase (MT1-MMP) plays pivotal roles in tumor progression and metastasis, and holds great promise as an early biomarker for malignant tumors. Therefore, the ability to evaluate MT1-MMP expression could be valuable for molecular biological and clinical studies. For this purpose, we aimed to develop short peptide-based nuclear probes because of their facile radiosynthesis, chemically uniform structures, and high specific activity, as compared to antibody-based probes, which could allow them to be more effective for in vivo MT1-MMP imaging. To the best of our knowledge, there have been no reports of radiolabeled peptide probes for the detection of MT1-MMP in cancer tissues. In this study, we designed and prepared four probes which consist of a MT1-MMP-specific binding peptide sequence (consisting of L or D amino acid isomers) and an additional cysteine (at the N or C-terminus) for conjugation with N-(m-[(123/125)I]iodophenyl) maleimide. We investigated probe affinity, probe stability in mice plasma, and probe biodistribution in tumor-bearing mice. Finally, in vivo micro single photon emission computed tomography (SPECT) imaging and ex vivo autoradiography were performed. Consequently, [(123)I]I-DC, a D-form peptide probe radioiodinated at the C-terminus, demonstrated greater than 1000-fold higher specific activity than previously reported antibody probes, and revealed comparably moderate binding affinity. [(125)I]I-DC showed higher stability as expected, and [(123)I]I-DC successfully identified MT1-MMP expressing tumor tissue by SPECT imaging. Furthermore, ex vivo autoradiographic analysis revealed that the radioactivity distribution profiles corresponded to MT1-MMP-positive areas. These findings suggest that [(123)I]I-DC is a promising peptide probe for the in vivo detection of MT1-MMP in cancers.}, } @article {pmid26323933, year = {2015}, author = {Zhu, MZ and Yu, XF and He, XM and Feng, WL and Fan, JH and Li, J and Xu, F and Tang, ZH and Zhang, BN and Qiao, YL and Zheng, S and Yang, HJ}, title = {Clinicopathological features of invasive lobular carcinoma of the breast: A nationwide multicenter study in China.}, journal = {Journal of cancer research and therapeutics}, volume = {11 Suppl 1}, number = {}, pages = {C89-94}, doi = {10.4103/0973-1482.163851}, pmid = {26323933}, issn = {1998-4138}, mesh = {Adult ; Biomarkers ; Breast Neoplasms/*epidemiology/metabolism/*pathology ; Carcinoma, Lobular/*epidemiology/metabolism/*pathology ; China/epidemiology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To analyze the clinicopathological features of invasive lobular carcinoma (ILC) and compare them with invasive ductal carcinoma (IDC), hoping to find the fact of ILC in China and assist the decision makers with proper individualized treatment.

MATERIALS AND METHODS: A nationwide multicenter retrospective study was performed. A total of 4211 primary breast cancer cases were randomly selected from 1999 to 2008 in seven regions of China. ILC cases were compared with IDC by clinicopathological features and molecular subtypes.

RESULTS: A total of 135 (3.2%) ILC and 3471 (82.4%) IDC cases were included for analysis. The age, tumor size, menopausal state, family history, nodal status, and stage of ILC were similar to that of IDC. ILC was more likely to be positive for estrogen receptor (65.5% vs. 57.7%) and progesterone receptor (64.7% vs. 58.5%), and less likely to overexpress human epidermal growth factor receptor-2 (17.3% vs. 23.6%). Even though, these differences are not significant, the proportion of luminal A type of ILC is significantly larger than that of IDC (54.8% vs. 42.7%; P < 0.05).

CONCLUSION: ILC has a larger proportion of luminal A type compared with IDC. Larger sample size study for better known of molecular subtypes of ILC is needed in future to individualize the treatment decision.}, } @article {pmid26321244, year = {2015}, author = {do Nascimento, JC and Ferreira, Sde A and Vasconcelos, JL and da Silva-Filho, JL and Barbosa, BT and Bezerra, MF and Rocha, CR and Beltrão, EI}, title = {Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression.}, journal = {Experimental and molecular pathology}, volume = {99}, number = {3}, pages = {409-415}, doi = {10.1016/j.yexmp.2015.08.015}, pmid = {26321244}, issn = {1096-0945}, mesh = {Brazil ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Female ; Fucosyltransferases/*genetics/metabolism ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Immunohistochemistry/methods ; Lewis X Antigen/metabolism ; *Promoter Regions, Genetic ; }, abstract = {Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (-6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (-6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil.}, } @article {pmid26321021, year = {2015}, author = {Santangelo, G and Vitale, C and Picillo, M and Moccia, M and Cuoco, S and Longo, K and Pezzella, D and di Grazia, A and Erro, R and Pellecchia, MT and Amboni, M and Trojano, L and Barone, P}, title = {Mild Cognitive Impairment in newly diagnosed Parkinson's disease: A longitudinal prospective study.}, journal = {Parkinsonism & related disorders}, volume = {21}, number = {10}, pages = {1219-1226}, doi = {10.1016/j.parkreldis.2015.08.024}, pmid = {26321021}, issn = {1873-5126}, mesh = {Aged ; Cognitive Dysfunction/*epidemiology ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*psychology ; Prevalence ; Prospective Studies ; }, abstract = {INTRODUCTION: In PD, Mild Cognitive Impairment (PD-MCI) occurs since early stages of disease. The aims were to assess presence of PD-MCI in untreated, drug-naive PD patients, and to follow-up the sample over 4 years to ascertain evolution of neurocognitive profile.

METHODS: Seventy-six patients underwent neuropsychological testing at baseline (T0), and after 2 (T1:n = 62) and 4 years (T2:n = 55). Diagnosis of PD-MCI and PD-associated dementia (PDD) was made according to current consensus criteria.

RESULTS: PD-MCI occurred in 25/76 patients (32.9%) at baseline, and 4 of them reverted from PD-MCI to Normal Cognition (Reverters), 7 remained stable (Non-Reverters) and 2 developed PDD at T2; 12 patients were lost to the follow-up. Among the 51 patients with normal cognition (PD-CN) at T0, 27 had normal cognition at T2 (5 of them were Reverters with respect to diagnosis at T1), 5 had MCI at T1 and T2 (Non-Reverters), 9 had MCI at T2 only, whereas 1 developed PDD; 9 patients were lost to the follow-up. At baseline, Reverters (n = 9) had younger age at onset and better performance on constructional visuospatial task than Non-Reverters (n = 12). Compared to patients without PD-MCI at all evaluations (n = 19), Reverters had poorer performance on verbal immediate recall and attention tasks and higher level of apathy at T0. Reduced performance on the Stroop Test at baseline predicted PD-MCI at T2.

CONCLUSION: Executive dysfunctions predicted development of PD-MCI after few years from onset. Reversal from PD-MCI to PD-CN was related to young age at onset and high level of apathy at baseline evaluation.}, } @article {pmid26320758, year = {2016}, author = {Ben-David, BM and Icht, M}, title = {Voice Changes in Real Speaking Situations During a Day, With and Without Vocal Loading: Assessing Call Center Operators.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {30}, number = {2}, pages = {247.e1-11}, doi = {10.1016/j.jvoice.2015.04.002}, pmid = {26320758}, issn = {1873-4588}, mesh = {Acoustics ; Adolescent ; Adult ; Case-Control Studies ; Female ; Habits ; Humans ; Life Style ; Male ; Occupational Diseases/diagnosis/etiology/*physiopathology ; *Occupational Health ; *Occupations ; Risk Factors ; *Speech Acoustics ; Speech Production Measurement ; Surveys and Questionnaires ; *Telephone ; Time Factors ; Voice Disorders/diagnosis/etiology/*physiopathology ; *Voice Quality ; Workload ; Young Adult ; }, abstract = {OBJECTIVES: Occupational-related vocal load is an increasing global problem with adverse personal and economic implications. We examined voice changes in real speaking situations during a single day, with and without vocal loading, aiming to identify an objective acoustic index for vocal load over a day.

METHODS: Call center operators (CCOs, n = 27) and age- and gender-matched students (n = 25) were recorded at the beginning and at the end of a day, with (CCOs) and without (students) vocal load. Speaking and reading voice samples were analyzed for fundamental frequency (F0), sound pressure level (SPL), and their variance (F0 coefficient of variation [F0 CV], SPL CV). The impact of lifestyle habits on voice changes was also estimated.

RESULTS AND CONCLUSIONS: The main findings revealed an interaction, with F0 rise at the end of the day for the students but not for the CCOs. We suggest that F0 rise is a typical phenomenon of a day of normal vocal use, whereas vocal loading interferes with this mechanism. In addition, different lifestyle profiles of CCOs and controls were observed, as the CCOs reported higher incidence of dehydrating behaviors (eg, smoking, caffeine). Yet, this profile was not linked with voice changes. In sum, we suggest that F0 rise over a day can potentially serve as an index for typical voice use. Its lack thereof can hint on consequent voice symptoms and complaints.}, } @article {pmid26319586, year = {2016}, author = {Liu, W and Tang, C and Liu, L and Zhu, QS and Huang, LF}, title = {Cervical intervertebral disc calcification with extreme lateral herniation in a child: T2-weighted signal intensity of the involved disc can be restored to normal.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {32}, number = {4}, pages = {749-752}, pmid = {26319586}, issn = {1433-0350}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Calcinosis/*complications/diagnostic imaging/drug therapy ; Child ; Female ; Humans ; Imaging, Three-Dimensional ; Intervertebral Disc Degeneration/*complications/diagnostic imaging/drug therapy ; Longitudinal Studies ; Magnetic Resonance Imaging ; Tomography Scanners, X-Ray Computed ; }, abstract = {PURPOSE: The purpose of this case report is to present a very atypical case of cervical intervertebral disc calcification (IDC) with extreme lateral herniated calcification in a child. This is the first ever reported case in which T2-weighted signal intensity of the involved disc was restored to normal after a 2-year follow-up.

METHODS: A 10-year-old girl presented with neck pain and right upper limb numbness for 2 months. The initial computed tomography (CT) images on admission showed calcified nucleus pulposus with extreme lateral herniated calcification at the C6-C7 level. Meanwhile, T2-weighted magnetic resonance imaging (MRI) revealed decreased signal intensity of the involved disc. The patient was treated conservatively with nonsteroidal anti-inflammatory drugs and jaw-occipital belt traction for 2 weeks. The cervical CT and MRI scans were repeated at 2-year follow-up.

RESULTS: Her clinical symptoms were completely resolved after 2 weeks. At 2-year follow-up, CT and MRI images demonstrated that calcification was completely absorbed and T2-weighted signal intensity of the C6-C7 disc was restored back to normal.

CONCLUSION: Cervical IDC combined with extreme lateral herniated calcification is extremely rare in children. The recovery of signal intensity of intervertebral disc on MRI may provide further support to the feasibility of conservative treatment of IDC.}, } @article {pmid26319120, year = {2015}, author = {Buas, MF and Rho, JH and Chai, X and Zhang, Y and Lampe, PD and Li, CI}, title = {Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {2}, pages = {445-454}, pmid = {26319120}, issn = {1573-7217}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; U01CA152637/CA/NCI NIH HHS/United States ; HHSN268201100046C/HL/NHLBI NIH HHS/United States ; HHSN268201100003C/WH/WHI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; HHSN271201100004C/AG/NIA NIH HHS/United States ; HHSN268201100002C/WH/WHI NIH HHS/United States ; U01 CA152746/CA/NCI NIH HHS/United States ; U01 CA152637/CA/NCI NIH HHS/United States ; T32CA009168/CA/NCI NIH HHS/United States ; HHSN268201100001C/WH/WHI NIH HHS/United States ; HHSN268201100004C/WH/WHI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*metabolism ; Breast Neoplasms/blood/*diagnosis/*metabolism ; Carcinoma, Ductal, Breast/blood/*diagnosis/*metabolism ; Case-Control Studies ; Computational Biology/methods ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Proteome ; Proteomics/methods ; ROC Curve ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Risk Factors ; }, abstract = {Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of clinically useful blood-based biomarkers for risk assessment and early detection. The objective of this study was to identify novel protein markers for ER+/PR+ ductal BC. A nested case-control study was conducted within the Women's Health Initiative observational study. Pre-clinical plasma specimens, collected up to 12.5 months before diagnosis from 121 cases and 121 matched controls, were equally divided into training and testing sets and interrogated using a customized antibody array targeting >2000 proteins. Statistically significant differences (P < 0.05) in matched case versus control signals were observed for 39 candidates in both training and testing sets, and four markers (CSF2, RYBP, TFRC, ITGB4) remained significant after Bonferroni correction (P < 2.03 × 10(-5)). A multivariate modeling procedure based on elastic net regression with Monte Carlo cross-validation achieved an estimated AUC of 0.75 (SD 0.06). Most candidates did not overlap with those described previously for triple-negative BC, suggesting sub-type specificity. Gene set enrichment analyses identified two GO gene sets as upregulated in cases-microtubule cytoskeleton and response to hormone stimulus (P < 0.05, q < 0.25). This study has identified a pool of novel candidate plasma protein biomarkers for ER+/PR+ ductal BC using pre-diagnostic biospecimens. Further validation studies are needed to confirm these candidates and assess their potential clinical utility for BC risk assessment/early detection.}, } @article {pmid26318821, year = {2015}, author = {Kim, JY and Seo, HB and Park, S and Moon, JI and Lee, JW and Lee, NK and Lee, SW and Bae, YT}, title = {Early-stage invasive ductal carcinoma: Association of tumor apparent diffusion coefficient values with axillary lymph node metastasis.}, journal = {European journal of radiology}, volume = {84}, number = {11}, pages = {2137-2143}, doi = {10.1016/j.ejrad.2015.08.009}, pmid = {26318821}, issn = {1872-7727}, mesh = {Adult ; Aged ; Axilla/*pathology ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/*pathology ; Diffusion Magnetic Resonance Imaging/methods ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis/pathology ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Retrospective Studies ; }, abstract = {PURPOSE: To evaluate any association between tumor apparent diffusion coefficient (ADC) values and axillary lymph node metastasis (ALNM) in early-stage invasive ductal carcinoma.

MATERIALS AND METHODS: Records of 270 invasive ductal carcinoma patients with stages T1 and T2 disease who underwent breast magnetic resonance imaging, including diffusion-weighted imaging with b values of 0 and 1000s/mm(2) were reviewed retrospectively. The tumor ADC values were analyzed for their utility in predicting ALNM using multivariate regression analysis and receiver operating characteristic (ROC) curve analysis.

RESULTS: Of the 270 patients, 58 (21.5%) experienced ALNM. The mean tumor ADC values were significantly lower in patients with ALNM than in those without metastasis (0.880 × 10(-3) vs. 0.999 × 10(-3)mm(2)/s, P<0.001). A ROC curve demonstrated a tumor ADC value of 0.991 × 10(-3)mm(2)/s to be the optimal cut-off for predicting ALNM. In a multivariate analysis, lower tumor ADC (≤ 0.991 × 10(-3)mm(2)/s; adjusted odds ratio (OR)=5.861, P<0.001), large tumor size (>2 cm; adjusted OR=3.156, P=0.002) and the presence of lymphovascular invasion (adjusted OR=4.125, P<0.001) were independent variables associated with ALNM. When tumor ADC value was added to known risk factors (i.e., tumor size and lymphovascular invasion), a significant improvement in the accuracy of risk prediction for axillary node metastasis was shown (c-statistic=0.758 vs. 0.816, P=0.026).

CONCLUSION: In early-stage invasive ductal carcinoma, lower tumor ADC values are associated with the presence of ALNM.}, } @article {pmid26316476, year = {2015}, author = {Uçmak Vural, G and Şahiner, I and Demirtaş, S and Efetürk, H and Demirel, BB}, title = {Sentinel Lymph Node Detection in Contralateral Axilla at Initial Presentation of a Breast Cancer Patient: Case Report.}, journal = {Molecular imaging and radionuclide therapy}, volume = {24}, number = {2}, pages = {90-93}, pmid = {26316476}, issn = {2146-1414}, abstract = {The main basin for breast lymphatic drainage is ipsilateral axilla. However, extra-axillary drainage may be seen in some patients. The most common extra-axillary site is internal mammary chain, while contralateral axillary drainage is an extremely rare situation in previously untreated patients. We describe a case of untreated right breast retroareolar carcinoma with contralateral axillary drainage detected on preoperative lymphoscintigraphy. Contralateral axillary dissection was performed based on the result of frozen section examination of the sentinel lymph node (SLN) which turned out to burden micrometastasis. Postoperative histopathological examination revealed invasive ductal carcinoma metastasis in 17 out of 22 lymph nodes from the ipsilateral axillary dissection, whereas 14 lymph nodes from contralateral axillary dissection other than the SLN were nonmetastatic. In our opinion, determination of contralateral axillary metastasis in primary staging process had a major contribution to the management of the patient.}, } @article {pmid26316122, year = {2015}, author = {Gordon, N and Skinner, AM and Pommier, RF and Schillace, RV and O'Neill, S and Peckham, JL and Muller, P and Condron, ME and Donovan, C and Naik, A and Hansen, J and Pommier, SJ}, title = {Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.}, journal = {Stem cell research & therapy}, volume = {6}, number = {1}, pages = {157}, pmid = {26316122}, issn = {1757-6512}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cells, Cultured ; Female ; *Glycolysis ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells/*metabolism ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; *Transcriptome ; }, abstract = {INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response.

METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test.

RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression.

CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.}, } @article {pmid26310238, year = {2015}, author = {Maruyama, T and Nakasone, T and Maruyama, N and Matayoshi, A and Arasaki, A}, title = {Synchronous quadruple multiple primary cancers of the tongue, bilateral breasts, and kidney in a female patient with a disease-free survival time of more than 5 years: a case report.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {263}, pmid = {26310238}, issn = {1477-7819}, mesh = {Aged ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Renal Cell/*mortality/pathology/surgery ; Carcinoma, Squamous Cell/*mortality/pathology/surgery ; Female ; Humans ; Kidney Neoplasms/*mortality/pathology/surgery ; Neoplasm Staging ; Neoplasms, Multiple Primary/*mortality/pathology/surgery ; Prognosis ; Survival Rate ; Tongue Neoplasms/*mortality/pathology/surgery ; }, abstract = {BACKGROUND: Reports of synchronous multiple primary cancers in patients with oral cancer have recently been increasing because of progress in radiographic diagnostic techniques. Multiple primary cancers in patients with oral cavity cancer mainly occur in the head and neck region, lung, and esophagus. 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is usually used to identify synchronous multiple primary cancers.

CASE PRESENTATION: We herein describe a 69-year-old woman diagnosed with synchronous quadruple multiple primary cancers, namely a squamous cell carcinoma of the mobile tongue, invasive ductal carcinoma of the right breast, intraductal carcinoma of the left breast, and chromophobe renal cell carcinoma of the right kidney. We removed the four tumors over three surgical procedures to reduce the surgical risk because the patient had diabetes mellitus. To the best of our knowledge, this combination of multiple primary cancers has not been reported to date. Importantly, we followed this case for 5 years after surgery. The patient was alive and well with no clinical or radiologic signs of recurrent or metastatic disease at the time of this writing.

CONCLUSIONS: In the present case, the kidney cancer could not be detected by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography but could be detected by contrast-enhanced computed tomography. To avoid overlooking multiple primary cancers of the kidney, we suggest that contrast-enhanced computed tomography should cover a region extending to the inferior margin of the kidney, rather than only to the liver, in patients with oral cavity cancer.}, } @article {pmid26298632, year = {2015}, author = {Kapucuoğlu, N and Bozkurt, KK and Başpınar, Ş and Koçer, M and Eroğlu, HE and Akdeniz, R and Akçil, M}, title = {The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1 expressions in invasive ductal carcinoma of the breast: CD44/CD24 expression in breast cancer.}, journal = {Pathology, research and practice}, volume = {211}, number = {10}, pages = {740-747}, doi = {10.1016/j.prp.2015.05.011}, pmid = {26298632}, issn = {1618-0631}, mesh = {AC133 Antigen ; Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase 1 Family ; Antigens, CD/*metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/*pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Glycoproteins/*metabolism ; Humans ; Hyaluronan Receptors/*metabolism ; Immunohistochemistry/methods ; Isoenzymes/*metabolism ; Middle Aged ; Peptides/*metabolism ; Prognosis ; Retinal Dehydrogenase/*metabolism ; }, abstract = {BACKGROUND: Recently, there are several studies about cancer stem cells (CSC), indicating that they are the cells that initiate the tumor, provide progression, metastasis and responsible for the aggressive tumor behavior.

MATERIALS AND METHODS: The purpose of this study is to investigate the expressions of CD24, CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma. Their relationships with clinicopathologic parameters, such as tumor grade, lymphovascular invasion, tumor size, axillary lymph node involvement, stage, hormone receptors, HER2 expression, basal like tumors, triple negative status and prognosis were also investigated. Tissue microarray method was used to investigate ımmunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105 invasive ductal carcinoma cases.

RESULTS: CD133 expression was significantly associated with tumor size (p=0.023) and stage (p=0.009). CD133 expression was decreased in tumors with larger tumor size, higher stage and lymphovascular invasion. CD133 expression was positively correlated with CD44 (r=0.212, p=0.032) and CD44(+)/CD24(+) (r=0.202, p=0.040) expressions. CD44, CD24 and ALDH1 expressions showed no significant relationship and correlation with clinicopathologic features. There was a significant relationship (p=0.048) between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was positively correlated with CD44(+)/CD24(-/low) phenotype (r=0.211, p=0.036).

CONCLUSIONS: Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low) phenotype. CD133 can detect a different population of CSC in breast carcinoma.}, } @article {pmid26295674, year = {2015}, author = {Conners, AL and Jones, KN and Hruska, CB and Geske, JR and Boughey, JC and Rhodes, DJ}, title = {Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.}, journal = {AJR. American journal of roentgenology}, volume = {205}, number = {3}, pages = {W374-81}, pmid = {26295674}, issn = {1546-3141}, support = {UL1 RR024150/RR/NCRR NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Lobular/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; *Molecular Imaging ; Radiopharmaceuticals ; Retrospective Studies ; Sensitivity and Specificity ; Technetium Tc 99m Sestamibi ; }, abstract = {OBJECTIVE: The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles.

MATERIALS AND METHODS: Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests.

RESULTS: In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients.

CONCLUSION: Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.}, } @article {pmid26294295, year = {2015}, author = {Hogan, MP and Goldman, DA and Dashevsky, B and Riedl, CC and Gönen, M and Osborne, JR and Jochelson, M and Hudis, C and Morrow, M and Ulaner, GA}, title = {Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {56}, number = {11}, pages = {1674-1680}, pmid = {26294295}, issn = {1535-5667}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Bone and Bones/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Carcinoma, Lobular/*diagnostic imaging ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Interpretation, Computer-Assisted ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis/diagnostic imaging ; Neoplasm Staging/*methods ; Positron-Emission Tomography/*methods ; Radiography ; *Radiopharmaceuticals ; Retrospective Studies ; }, abstract = {UNLABELLED: Although guidelines such as those of the National Comprehensive Cancer Network consider (18)F-FDG PET/CT for systemic staging of newly diagnosed stage III breast cancer patients, factors in addition to stage may influence the utility of PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than invasive ductal carcinoma (IDC) on (18)F-FDG PET, we hypothesized that tumor histology may be one such factor. We evaluated PET/CT systemic staging of patients newly diagnosed with ILC compared with IDC.

METHODS: In this Institutional Review Board-approved retrospective study, our Hospital Information System was screened for ILC patients who underwent PET/CT in 2006-2013 before systemic or radiation therapy. Initial stage was determined from examination, mammography, ultrasound, MR, or surgery. PET/CT was performed to identify unsuspected distant metastases. A sequential cohort of stage III IDC patients was evaluated for comparison. Upstaging rates were compared using the Pearson χ(2) test.

RESULTS: The study criteria were fulfilled by 146 ILC patients. PET/CT revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I, 2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged only by the CT component of the PET/CT, as the metastases were not (18)F-FDG-avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were upstaged to IV by PET/CT. All 20 demonstrated (18)F-FDG-avid metastases. The relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC patients was 1.98 times (95% confidence interval, 0.98-3.98) that of stage III ILC patients (P = 0.049). For (18)F-FDG-avid metastases, the relative risk of PET/CT revealing unsuspected (18)F-FDG-avid distant metastases in stage III IDC patients was 2.82 times (95% confidence interval, 1.26-6.34) that of stage III ILC patients (P = 0.007).

CONCLUSION: (18)F-FDG PET/CT was more likely to reveal unsuspected distant metastases in stage III IDC patients than in stage III ILC patients. In addition, some ILC patients were upstaged by non-(18)F-FDG-avid lesions visible only on the CT images. Overall, the impact of PET/CT on systemic staging may be lower for ILC patients than for IDC patients.}, } @article {pmid26290094, year = {2015}, author = {Dobbs, JL and Mueller, JL and Krishnamurthy, S and Shin, D and Kuerer, H and Yang, W and Ramanujam, N and Richards-Kortum, R}, title = {Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {1}, pages = {105}, pmid = {26290094}, issn = {1465-542X}, support = {1R01EB01157/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; Breast/*pathology ; Breast Neoplasms/*pathology ; Contrast Media/administration & dosage ; Diagnosis, Differential ; Female ; Humans ; Microscopy, Confocal/methods ; Optical Imaging/methods ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Pathologists currently diagnose breast lesions through histologic assessment, which requires fixation and tissue preparation. The diagnostic criteria used to classify breast lesions are qualitative and subjective, and inter-observer discordance has been shown to be a significant challenge in the diagnosis of selected breast lesions, particularly for borderline proliferative lesions. Thus, there is an opportunity to develop tools to rapidly visualize and quantitatively interpret breast tissue morphology for a variety of clinical applications.

METHODS: Toward this end, we acquired images of freshly excised breast tissue specimens from a total of 34 patients using confocal fluorescence microscopy and proflavine as a topical stain. We developed computerized algorithms to segment and quantify nuclear and ductal parameters that characterize breast architectural features. A total of 33 parameters were evaluated and used as input to develop a decision tree model to classify benign and malignant breast tissue. Benign features were classified in tissue specimens acquired from 30 patients and malignant features were classified in specimens from 22 patients.

RESULTS: The decision tree model that achieved the highest accuracy for distinguishing between benign and malignant breast features used the following parameters: standard deviation of inter-nuclear distance and number of duct lumens. The model achieved 81 % sensitivity and 93 % specificity, corresponding to an area under the curve of 0.93 and an overall accuracy of 90 %. The model classified IDC and DCIS with 92 % and 96 % accuracy, respectively. The cross-validated model achieved 75 % sensitivity and 93 % specificity and an overall accuracy of 88 %.

CONCLUSIONS: These results suggest that proflavine staining and confocal fluorescence microscopy combined with image analysis strategies to segment morphological features could potentially be used to quantitatively diagnose freshly obtained breast tissue at the point of care without the need for tissue preparation.}, } @article {pmid26285240, year = {2015}, author = {Shih, J and Bashir, B and Gustafson, KS and Andrake, M and Dunbrack, RL and Goldstein, LJ and Boumber, Y}, title = {Cancer Signature Investigation: ERBB2 (HER2)-Activating Mutation and Amplification-Positive Breast Carcinoma Mimicking Lung Primary.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {13}, number = {8}, pages = {947-952}, pmid = {26285240}, issn = {1540-1413}, support = {R01 GM084453/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Brain Neoplasms/diagnosis/secondary/therapy ; Breast Neoplasms/diagnosis/drug therapy/*genetics ; Female ; *Gene Amplification ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/therapy ; *Mutation ; Neoplasm Staging ; Neoplasms, Second Primary ; Radiography, Thoracic ; Radiosurgery ; Receptor, ErbB-2/*genetics ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Next-generation sequencing of primary and metachronous metastatic cancer lesions may impact patient care. We present a case of relapsed metastatic breast cancer with a dominant pulmonary lesion originally identified as lung adenocarcinoma. A 72-year-old, never-smoker woman with a protracted cough was found to have a large lung mass and regional lymphadenopathy on a chest CT. Lung mass biopsy showed adenocarcinoma with focal TTF-1 (thyroid transcription factor 1) positivity, favoring a lung primary. In addition to stereotactic brain radiation for cerebral metastases, she was started on carboplatin/pemetrexed. As part of the workup, the tumor was analyzed by a 50-gene targeted mutation panel, which detected 3 somatic mutations: ERBB2 (HER2) D769H activating missense mutation, TP53 Y126 inactivating truncating mutation, and SMARCB1 R374Q missense mutation. Of note, the patient had a history of stage IIA triple-negative grade 3 invasive ductal carcinoma of the left breast 1.5 years ago and received neoadjuvant chemotherapy and adjuvant radiation, and underwent a lumpectomy. Further analysis of her primary breast tumor showed a mutational profile identical to that of the lung tumor. Fluorescence in situ hybridization revealed HER2 amplification in the lung tumor, with a HER2/CEP17 ratio of 3.9. The patient was diagnosed with recurrent HER2-positive metastatic breast carcinoma with a coexisting ERBB2 (HER2) activating mutation. Chemotherapy was adjusted to include dual HER2-targeted therapy containing trastuzumab and pertuzumab, resulting in an ongoing partial response. This case demonstrates that a unique genetic mutational profile can clarify whether a tumor represents a metastatic lesion or new malignancy when conventional morphological and immunohistochemical methods are indeterminate, and can directly impact treatment decisions.}, } @article {pmid26280894, year = {2015}, author = {Kim, H and Lee, KH and Park, IA and Chung, YR and Im, SA and Noh, DY and Han, W and Moon, HG and Jung, YY and Ryu, HS}, title = {Expression of SIRT1 and apoptosis-related proteins is predictive for lymph node metastasis and disease-free survival in luminal A breast cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {467}, number = {5}, pages = {563-570}, pmid = {26280894}, issn = {1432-2307}, mesh = {Adult ; Aged ; *Apoptosis ; Breast Neoplasms/*metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Sentinel Lymph Node Biopsy ; Sirtuin 1/*metabolism ; }, abstract = {Luminal A breast cancer can present with early, unexpected lymph node metastasis, and sentinel lymph node biopsy has been reported false negative in some cases. We aimed to construct a biomarker-based model that predicts lymph node metastasis in luminal A breast cancer, using expression of silent mating type information regulation 2 homolog 1 (SIRT1) and apoptosis-related factors, which are known to be closely related. We selected tissue samples of 278 cases of luminal A invasive ductal carcinoma, constructed tissue microarrays, and performed immunohistochemical staining for SIRT1 and four apoptosis-related proteins. In constructing the best predictive model for lymph node metastasis, six clinicopathological parameters and five molecular markers were considered. Independent factors predictive of lymph node metastasis were pT stage (OR 1.829, p = 0.027), lymphovascular invasion (OR 4.128, p < 0.001), and decreased expression of caspase-3 (OR 0.535, p = 0.034) and of SIRT1 (OR 0.526, p = 0.053). A combination nuclear grade, lymphovascular invasion, increased B-cell lymphoma 2 (Bcl-2) expression, and reduced expression of caspase-3 and of SIRT1 yielded the strongest predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.696. This combination was also predictive of shortened disease-free survival (73.1 vs. 67.7 months, p = 0.003). Our data support a role of SIRT1 protein as tumor suppressor in luminal A breast cancer, in association with apoptosis-related proteins. Our model based upon a combination of these biomarkers is expected to increase accuracy of prediction of lymph node metastasis in luminal A breast cancer. This might serve as a valuable tool in determining the optimal surgical strategy in breast cancer patients.}, } @article {pmid26279752, year = {2015}, author = {Qian, L and Chen, W and Sun, W and Li, M and Zheng, R and Qian, Q and Lv, L}, title = {Antimicrobial peptide LL-37 along with peptidoglycan drive monocyte polarization toward CD14(high)CD16(+) subset and may play a crucial role in the pathogenesis of psoriasis guttata.}, journal = {American journal of translational research}, volume = {7}, number = {6}, pages = {1081-1094}, pmid = {26279752}, issn = {1943-8141}, abstract = {The human cathelicidin LL-37 peptide is overexpressed in psoriasis and has been demonstrated to be a multifunctional modulator of innate immune response elements, including monocytes. Monocytes, categorized into three populations based on the cell surface expression of CD14 and CD16, are activated in psoriasis guttate and are commonly triggered by streptococcal infections. Peptidoglycan (PGN) is a major cell-wall component of streptococcus, and an increasing number of PGN-containing cells have been detected in psoriasis. Since there are independent reports of both PGN and LL-37 influencing monocytes, we tried to evaluate the effect of human LL-37 on PGN-induced monocyte activity and differentiation and subsequently studied their correlation with the pathogenesis of psoriasis guttate. The results revealed that monocytes from the peripheral blood of healthy individuals resulted in their polarization toward the CD14(high)CD16(+) subset, when cultured with PGN in the presence of the LL-37 peptide. This peptide further induced PGN-driven differentiated monocytes into immature dendritic cells (iDC), as evident by the increased expression of CD1a, CD86, and HLA-DR markers, resulting in the induction of T cell proliferation and Th17 polarization. Furthermore, our data suggested that psoriasis guttata patients have significantly higher percentages of CD14(high)CD16(+) monocytes as well as circulating levels of LL-37, soluble form of triggering receptor expressed on myeloid cells (sTREM-1) levels, and anti-streptolysin O (ASO) levels, as compared to healthy controls. Psoriasis guttata patients also showed a positive correlation between the percentage of CD14(high)CD16(+) monocytes and the serum levels of sTREM-1 as well as the Psoriasis Area and Severity Index (PASI) scores. Therefore, we concluded that LL-37 in synergy with PGN directs monocyte polarization and differentiation into a proinflammatory phenotype, which might play a crucial role in the pathogenesis of psoriasis.}, } @article {pmid26273414, year = {2015}, author = {Huo, Z and Gao, Y and Zuo, W and Zheng, G and Kong, R}, title = {Metastases of basal-like breast invasive ductal carcinoma to the endometrium: A case report and review of the literature.}, journal = {Thoracic cancer}, volume = {6}, number = {4}, pages = {548-552}, pmid = {26273414}, issn = {1759-7706}, abstract = {We present a case of single endometrial metastasis from breast invasive ductal cancer. This case was unique because the immunohistochemical staining was negative for human epidermal growth factor receptor 2/neu and estrogen and progesterone receptors, and positive for cytokeratin 5/6 and epidermal growth factor receptor in the primary and metastatic tumor cells. No gross evidence of tumor was observed in other sites. We identified 12 cases of metastases to the endometrium from breast carcinoma from series and case reports in the literature between 1985 and 2014. This review indicated that hormone receptor-positive invasive lobular breast cancer cells are more likely to metastasize to the endometrium than other cell types in patients over 50 years of age.}, } @article {pmid26271144, year = {2015}, author = {Wang, X and Hu, B and Shen, H and Zhou, H and Xue, X and Chen, Y and Chen, S and Han, Y and Yuan, B and Zhao, H and Zhi, Q and Kuang, Y}, title = {Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {75}, number = {}, pages = {218-225}, doi = {10.1016/j.biopha.2015.07.038}, pmid = {26271144}, issn = {1950-6007}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Disease Progression ; Enhancer of Zeste Homolog 2 Protein ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm Staging ; Odds Ratio ; Polycomb Repressive Complex 2/*analysis ; Risk Factors ; Treatment Outcome ; Up-Regulation ; }, abstract = {The polycomb group protein enhancer of zeste homolog 2 (EZH2) is regarded as a tightly linking oncogene in many types of cancer. However, the prognostic role of EZH2 in breast cancer (BC) still remains controversial. Our study aimed to evaluate the clinical and prognostic relevance of EZH2 in BC patients based on published studies. 11 studies totally containing 2330 patients (1052 EZH2-positive and 1278 EZH2-negative) were included in our meta-analysis. Our data showed that EZH2 over-expression was significantly associated with estrogen receptor (ER) negativity [OR=0.227, 95% CI=0.174-0.297, P=0.000], progesterone receptor (PR) negativity [OR=0.454, 95% CI=0.300-0.687, P=0.000], human epidermal growth factor receptor type 2 (HER-2) positivity [OR=1.846, 95% CI=1.366-2.496, P=0.000], invasive ductal cancer (IDC) [OR=2.237, 95% CI=1.489-3.361, P=0.000], race (Caucasian) [OR=0.707, 95% CI=0.522-0.957, P=0.025], high histological grade [OR=3.177, 95% CI=2.012-5.014, P=0.000] and triple-negative status (TNBCs) [OR=5.380, 95% CI=1.065-27.187, P=0.042], which led to a poor OS rate in BC [RR=2.193, 95% CI=1.495-3.217, P=0.000]. In conclusion, EZH2 participated in the progression of BC as a putative factor, and over-expression of EZH2 was distinctly correlated with a poor patient survival. EZH2 may serve as a prognostic biomarker and target in BC patients.}, } @article {pmid26269162, year = {2015}, author = {Yang, T and Zhang, Z and Liu, G and Mu, D and Sun, X and Chen, Z and Liu, Y and Wang, C and Sun, X and Wang, Y}, title = {[Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in breast cancer with three-dimensional reconstruction technique].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {53}, number = {4}, pages = {280-284}, pmid = {26269162}, issn = {0529-5815}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/*diagnosis/drug therapy ; Female ; Humans ; *Imaging, Three-Dimensional ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm, Residual/*diagnosis ; Prospective Studies ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: To evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique.

METHODS: This was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis.

RESULTS: The longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³).

CONCLUSION: 3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.}, } @article {pmid26268905, year = {2016}, author = {Rominger, M and Berg, D and Frauenfelder, T and Ramaswamy, A and Timmesfeld, N}, title = {Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?.}, journal = {European radiology}, volume = {26}, number = {5}, pages = {1457-1465}, pmid = {26268905}, issn = {1432-1084}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Tumor Burden ; }, abstract = {OBJECTIVES: To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer.

MATERIALS AND METHODS: MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors.

RESULTS: Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86% (97/113), overestimation 9% (10/113) and underestimation 5% (6/113); BI-RADS mass lesions were overestimated in 7% (6/81) versus 41% (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3%) ILC did not enhance.

CONCLUSION: Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance.

KEY POINTS: • Execution and scope of MRI and histopathological size measurements influence concordance rate. • Non-mass like enhancement predicts discordance. • Additional high-risk lesions in proximity of tumour do not cause measurement discordance. • Low percentage of ILC do not enhance at all.}, } @article {pmid26255059, year = {2015}, author = {Rane, SU and Mirza, H and Grigoriadis, A and Pinder, SE}, title = {Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {1}, pages = {101-121}, doi = {10.1007/s10549-015-3509-x}, pmid = {26255059}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Aberrations ; Chromosome Mapping ; Computational Biology ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; Molecular Sequence Annotation ; Neoplasm Invasiveness ; Neurophysins/genetics ; Protein Precursors/genetics ; Signal Transduction ; Vasopressins/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a pre-invasive malignancy detected with an increasing frequency through screening mammography. One of the primary aims of therapy is to prevent local recurrence, as in situ or as invasive carcinoma, the latter arising in half of the recurrent cases. Reliable biomarkers predictive of its association with recurrence, particularly as invasive disease, are however lacking. In this study, we perform a meta-analysis of 26 studies which report somatic copy number aberrations (SCNAs) in 288 cases of 'pure' DCIS and 328 of DCIS associated with invasive carcinoma, along with additional unmatched cases of 145 invasive carcinoma of ductal/no special type (IDC) and 50 of atypical ductal hyperplasia (ADH). SCNA frequencies across the genome were calculated at cytoband resolution (UCSC genome build 19) to maximally utilize the available information in published literature. Fisher's exact test was used to identify significant differences in the gain-loss distribution in each cytoband in different group comparisons. We found synchronous DCIS to be at a more advanced stage of genetic aberrations than pure DCIS and was very similar to IDC. Differences in gains and losses in each disease process (i.e. invasive or in situ) at each cytoband were used to infer evidence of selection and conservation for each cytoband and to define an evolutionary conservation scale (ECS) as a tool to identify and distinguish driver SCNA from the passenger SCNA. Using ECS, we have identified aberrations that show evidence of selection from the early stages of neoplasia (i.e. in ADH and pure DCIS) and persist in IDC; we postulate these to be driver aberrations and that their presence may predict progression to invasive disease.}, } @article {pmid26253945, year = {2015}, author = {Tsai, KW and Li, GC and Chen, CH and Yeh, MH and Huang, JS and Tseng, HH and Fu, TY and Liou, HH and Pan, HW and Huang, SF and Chen, CC and Chang, HY and Ger, LP and Chang, HT}, title = {Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype.}, journal = {Breast cancer research and treatment}, volume = {153}, number = {1}, pages = {219-234}, doi = {10.1007/s10549-015-3525-x}, pmid = {26253945}, issn = {1573-7217}, mesh = {5-Methylcytosine/analogs & derivatives ; Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/*mortality/pathology ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; DNA-Binding Proteins/genetics/metabolism ; Dioxygenases ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Mixed Function Oxygenases ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Protein Transport ; Proto-Oncogene Proteins/genetics/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Risk Factors ; Survival Analysis ; Young Adult ; }, abstract = {DNA methylation at the 5 position of cytosine (5 mC) is an epigenetic hallmark in cancer. The 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5 mC, 5 hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5 mC, 5 hmC, TET1, and TET2 in the corresponding tumor adjacent normal (n = 309), ductal carcinoma in situ (DCIS, n = 120), and invasive ductal carcinoma (IDC, n = 309) tissues for 309 breast ductal carcinoma patients. 5 mC, 5 hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5 hmC was correlated with the cytoplasmic mislocalization of TET1 (p < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p = 0.003) and disease-free survival (DFS) (AHR 1.91, p = 0.006). The combined decrease of 5 mC and 5 hmC was correlated with worse DSS (AHR 2.19, p = 0.008) and DFS (AHR 1.99, p = 0.036). Stratification analysis revealed that the low level of 5 mC was associated with poor DSS (AHR 1.89, p = 0.044) and DFS (AHR 2.02, p = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5 hmC was associated with worse DSS (AHR 2.77, p = 0.002) and DFS (AHR 2.69, p = 0.006) for the ER/PR-negative subtype. The decreases of 5 mC, 5 hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5 hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.}, } @article {pmid26252312, year = {2015}, author = {Liu, XY and Jiang, YZ and Liu, YR and Zuo, WJ and Shao, ZM}, title = {Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.}, journal = {Medicine}, volume = {94}, number = {31}, pages = {e1309}, pmid = {26252312}, issn = {1536-5964}, mesh = {Adenocarcinoma/*mortality/*pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Retrospective Studies ; SEER Program ; Socioeconomic Factors ; Survival Rate ; United States/epidemiology ; Young Adult ; }, abstract = {Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P < 0.001). Five-year OS rates were 95.3% versus 90.1% (P < 0.001). After adjustment for common clinicopathological factors in the multivariate analysis, patients with ICC showed limited DSS advantage over the IDC group (HR = 0.75, 95% CI: 0.38-1.51, P = 0.421). No significant difference in DSS nor OS was observed in matched groups between ICC and IDC. Analysis among ER-positive patients revealed similar prognostic factors as among all patients. Survival analysis in different tumor grade subgroups showed no significant difference between ICC and IDC.ICCs have unique clinicopathological characteristics, higher rates of breast-conserving surgery, and more favorable prognosis compared to the overall IDC population. Difference in tumor grade between the 2 groups may partially explain the different outcome. Improved clinical and biological understanding of ICC might lead to more individualized and tailored therapy for breast cancer patients.}, } @article {pmid26245013, year = {2015}, author = {Jethava, A and Ali, S and Wakefield, D and Crowell, R and Sporn, J and Vrendenburgh, J}, title = {Diagnostic Accuracy of MRI in Predicting Breast Tumor Size: Comparative Analysis of MRI vs Histopathological Assessed Breast Tumor Size.}, journal = {Connecticut medicine}, volume = {79}, number = {5}, pages = {261-267}, pmid = {26245013}, issn = {0010-6178}, mesh = {Adenocarcinoma/pathology ; Adenocarcinoma, Mucinous/pathology ; Breast Neoplasms/*pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Carcinoma, Papillary/pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Diagnostic accuracy of MRI in predicting breast tumor size: comparative analysis of breast tumor size byMRI vs histopathological assessment.

PURPOSE: Tumor size is one of the most important factors in making a clinical and pathological assessment of breast cancer. The purpose of this study is to evaluate if MRI imaging is helpful for the surgeon in the preoperative accurate assessment of tumor size.

METHODS: We retrospectively reviewed the charts of 124 patients who were diagnosed or managed at the Saint Francis /Mt. Sinai Regional Cancer Center. We then compared the preoperative MRI tumor size with the histopathological tumor size obtained at surgical resection. Tumors were divided into four histological groups: invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), ductal carcinomain situ (DCIS), and mixed tumors (including mucinous, papillary, tubular, and apocrine breast carcinoma). MRI measurement of tumor size was compared against the reference size obtained from the microscopic measurement of the largest diameter of tumors. Concordance was defined as a difference ≤ 0.5 cm between MRI and pathology.

RESULTS: A total of 124 patients with 147 breast tumors were included in our study. The mean age was 59.8 ± 12.72 years. Histologically, there were 81 IDC (55.10%), 35 DCIS (23.81%), 15 ILC (10.20%), and 16 mixed tumors (10.88%). Out of 147 tumors, 55.78% showed concordance of MRI and pathologic tumor size within 0.5 cm. MRI overestimated 31.97% and underestimated 12.24% of tumors.

CONCLUSION: Breast MRI provides an additional tool for preoperative assessment of tumor size. In our study, we noted 56% concordance between MRI with pathological tumor size within 0.5 cm. Several factors, including grading of tumor, cancer type, and size, strongly affect the accuracy of MRI in the preoperative assessment of tumor size. High-grade tumor and DCIS are the two strongest negative factors resulting in overestimation of tumor size on MRI.}, } @article {pmid26244023, year = {2015}, author = {Song, W and Xie, R and Zhu, A and Xu, Y and Shi, Y and Shen, Y and Zhang, W and Yang, F and Guan, X}, title = {p27(Kip1) and Ser10-phosphorylated p27(Kip1) in breast cancer: clinical significance and expression.}, journal = {OncoTargets and therapy}, volume = {8}, number = {}, pages = {1863-1869}, pmid = {26244023}, issn = {1178-6930}, abstract = {BACKGROUND: The protein p27 (p27(Kip1)) is a member of the cyclin-dependent kinase inhibitor family, which negatively regulates cell cycle progression, and the phosphorylation of p27 has been proven to affect its stability and nuclear export. Clinical studies on the relation between p27 and phosphorylated p27 (p-p27Ser10) in breast invasive ductal carcinomas are still scarce.

METHODS: We examined the expression of p27 and p-p27Ser10 using immunohistochemistry in 107 breast invasive ductal carcinomas and analyzed the relationship of these biomarkers and tumor characteristics.

RESULTS: Of the 107 tumor samples, 38.3% (41 of 107) overexpressed p27 and 64.5% (69 of 107) overexpressed p-p27Ser10. Analysis of correlation with clinical characteristics showed that high expression level of p-p27Ser10 was linked to poor differentiation, advanced disease stage, and lymph node metastasis, whereas a contrary trend was observed for p27 (all P<0.05). In addition, the expression of p-p27Ser10 was significantly higher in malignant tumors than in adjacent tissues, while p27 showed the opposite trend. Also, there were different levels of p27 and p-p27Ser10 in different types of breast cancer.

CONCLUSION: p27 and p-p27Ser10 are involved in the development of invasive ductal carcinoma and are potential indicators to judge the degree of malignancy as well as recurrence and metastasis.}, } @article {pmid26243303, year = {2015}, author = {Michoux, N and Van den Broeck, S and Lacoste, L and Fellah, L and Galant, C and Berlière, M and Leconte, I}, title = {Texture analysis on MR images helps predicting non-response to NAC in breast cancer.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {574}, pmid = {26243303}, issn = {1471-2407}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/drug therapy/pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI.

METHODS: Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC.

RESULTS: A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction.

CONCLUSION: Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.}, } @article {pmid26242364, year = {2015}, author = {McEvoy, MP and Coopey, SB and Mazzola, E and Buckley, J and Belli, A and Polubriaginof, F and Merrill, AL and Tang, R and Garber, JE and Smith, BL and Gadd, MA and Specht, MC and Guidi, AJ and Roche, CA and Hughes, KS}, title = {Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).}, journal = {Annals of surgical oncology}, volume = {22}, number = {10}, pages = {3346-3349}, doi = {10.1245/s10434-015-4747-1}, pmid = {26242364}, issn = {1534-4681}, mesh = {Adult ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; *Continuity of Patient Care ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Mammography ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*pathology ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {BACKGROUND: The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.

METHODS: A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed. Patient characteristics, pathology and follow-up were determined from chart review.

RESULTS: We identified 58 young women with atypical breast lesions. Median age at diagnosis was 31 years (range 19-34). 34 patients had ADH, 11 had ALH, 8 had LCIS, and 5 had severe ADH. 7 (12%) patients developed breast cancer. The median follow-up was 86 months (range 1-298). Median time to cancer diagnosis was 90 months (range 37-231). 4 cancers were on the same side, 3 were contralateral. 4 were IDC, 1 was ILC, and 2 were DCIS. Cancer was detected by screening mammogram in 4 patients, 2 by clinical exam, and 1 unknown. In the entire cohort, 26 (45%) patients had screening mammograms as part of their follow up, 12 patients had only clinical follow up, and 20 had no additional follow up. 13 patients required subsequent biopsies.

CONCLUSION: Young women with atypical breast lesions are at a markedly increased risk for developing breast cancer and should be followed closely. Based on our findings, we recommend close clinical follow-up, MRI starting at age 25 through age 29, and screening mammograms for those over 30 in this high-risk group of patients.}, } @article {pmid26240785, year = {2015}, author = {Vincze, B and Kapuvári, B and Udvarhelyi, N and Horváth, Z and Mátrai, Z and Czeyda-Pommersheim, F and Kőhalmy, K and Kovács, J and Boldizsár, M and Láng, I and Kásler, M}, title = {Serum estrone concentration, estrone sulfate/estrone ratio and BMI are associated with human epidermal growth factor receptor 2 and progesterone receptor status in postmenopausal primary breast cancer patients suffering invasive ductal carcinoma.}, journal = {SpringerPlus}, volume = {4}, number = {}, pages = {387}, pmid = {26240785}, issn = {2193-1801}, abstract = {BACKGROUND: We investigated in postmenopausal women with primary breast cancer prior to surgical intervention whether, serum levels of different steroid hormones and hormonal precursors associated with tumor tissue estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status.

METHODS: We enrolled 1,042 patients suffering invasive ductal carcinoma undergoing surgical resection in the National Institute of Oncology, Hungary between 2003 and 2011. Serum parameters were measured by RIA/IRMA assays; tumor tissue ER, PR and HER2 status was assessed histologically. Patients were classified according to tumor receptor status. Case-case analysis subjects were categorized into four subgroups based on serum hormone concentrations in ER, PR and HER2 receptor-negative cases, respectively.

RESULTS: Serum estrone sulfate and dehydroepiandrosterone sulfate levels correlated with each other and also with serum estrone and estradiol levels. According to case-case study the odds ratios in the highest quartile were 1.517 (p = 0.0305, Ptrend = 0.0394) for androstenedione, 1.495 (p = 0.0317, Ptrend < 0.0105) for estrone and 0.654 (p = 0.0273, Ptrend < 0.0151) for estrone sulfate/estrone ratio in PR+ vs. PR- tumors. Regarding HER2 status (HER2+ vs. HER2-), the odds ratios for estrone, estrone sulfate and estrone sulfate/estrone ratio were 0.530 (p = 0.0234, Ptrend = 0.0595), 2.438 (p = 0.0042, Ptrend < 0.0066) and 3.118 (p = 0.0001, Ptrend < 0.0001) in the highest quartile, respectively. Of note significantly increased BMI associates with PR+ and ER +/PR+ status while significantly decreased BMI was observed in HER2+ cases.

CONCLUSIONS: Taken together, measurement of serum estrone and estrone sulfate concentrations prior to surgical intervention might support the individualization of regime in postmenopausal primary breast cancer patients.}, } @article {pmid26233575, year = {2015}, author = {Broch, K and Murbræch, K and Andreassen, AK and Hopp, E and Aakhus, S and Gullestad, L}, title = {Contemporary Outcome in Patients With Idiopathic Dilated Cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {116}, number = {6}, pages = {952-959}, doi = {10.1016/j.amjcard.2015.06.022}, pmid = {26233575}, issn = {1879-1913}, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiac Resynchronization Therapy ; Cardiomyopathy, Dilated/complications/*therapy ; Cardiotonic Agents/therapeutic use ; Cohort Studies ; Death, Sudden, Cardiac/etiology/*prevention & control ; Defibrillators, Implantable ; Digitoxin/therapeutic use ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Exercise Test ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Oxygen Consumption ; Prospective Studies ; Stroke Volume ; Treatment Outcome ; Ventricular Dysfunction, Left/complications/*therapy ; }, abstract = {Outcome is better in patients with idiopathic dilated cardiomyopathy (IDC) than in ischemic heart failure (HF), but morbidity and mortality are nevertheless presumed to be substantial. Most data on the prognosis in IDC stem from research performed before the widespread use of current evidence-based treatment, including implantable devices. We report outcome data from a cohort of patients with IDC treated according to current HF guidelines and compare our results with previous figures: 102 consecutive patients referred to our tertiary care hospital with idiopathic IDC and a left ventricular ejection fraction <40% were included in a prospective cohort study. After extensive baseline work-up, follow-up was performed after 6 and 13 months. Vital status and heart transplantation were recorded. Over the first year of follow-up, the patients were on optimal pharmacological treatment, and 24 patients received implantable devices. Left ventricular ejection fraction increased from 26 ± 10% to 41 ± 11%, peak oxygen consumption increased from 19.5 ± 7.1 to 23.4 ± 7.8 ml/kg/min, and functional class improved substantially (all p values <0.001). After a median follow-up of 3.6 years, 4 patients were dead, and heart transplantation had been performed in 9 patients. According to our literature search, survival in patients with IDC has improved substantially over the last decades. In conclusion, patients with IDC have a better outcome than previously reported when treated according to current guidelines.}, } @article {pmid26231013, year = {2015}, author = {Nakash, O and Nagar, M and Kanat-Maymon, Y}, title = {Clinical use of the DSM categorical diagnostic system during the mental health intake session.}, journal = {The Journal of clinical psychiatry}, volume = {76}, number = {7}, pages = {e862-9}, doi = {10.4088/JCP.14m09214}, pmid = {26231013}, issn = {1555-2101}, mesh = {Adult ; Aged ; Aged, 80 and over ; Community Mental Health Services/*standards ; Depressive Disorder, Major/*diagnosis ; *Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Interview, Psychological/*standards ; Israel ; Male ; Middle Aged ; Young Adult ; }, abstract = {OBJECTIVE: The primary purpose of diagnostic systems is to improve the care of individuals suffering from mental disorders. Yet, few studies have explored the clinical use of the DSM. Here, we investigated clinicians' methods of obtaining and using diagnostic information during the mental health intake session. We examined the specific diagnostic information collected in usual care using unstructured interviews and the way this information was applied to make diagnostic decisions within naturalistic settings. We compared these decisions to diagnoses made using independent structured diagnostic interviews that served as the gold standard for psychiatric diagnosis. Finally, we examined ways to improve diagnostic efficiency by identifying the best probes for the diagnosis of major depressive disorder (MDD) in naturalistic settings.

METHOD: A total of 122 intake sessions in 4 community mental health clinics in Israel were audiotaped. Data were collected from October 2012 to April 2013. Immediately following the intake, clinicians listed the service user's diagnoses according to the DSM-IV while the service user completed a structured diagnostic interview with an independent interviewer. Recorded intake sessions were coded by independent clinicians using an information checklist.

RESULTS: Overall, clinicians tended to underuse the DSM, not collecting sufficient information to establish a correct diagnosis for most disorders. Accuracy of diagnostic decisions for MDD improved when only 2 screener items (depressed mood and diminished interest or pleasure) were assessed, compared to assessing 5 or more criteria as required by DSM-IV (diagnostic odds ratios = 9.44 and 3.85, respectively).

CONCLUSION: The problem of missing diagnostic information may underlie the poor reliability of the clinical diagnostic decision process. Systematically evaluating clinicians' assessment process in regular care can help identify the best probes to use in clinical practice to increase diagnostic efficiency.}, } @article {pmid26229954, year = {2015}, author = {Panisello-Tafalla, A and Clua-Espuny, JL and Gil-Guillen, VF and González-Henares, A and Queralt-Tomas, ML and López-Pablo, C and Lucas-Noll, J and Lechuga-Duran, I and Ripolles-Vicente, R and Carot-Domenech, J and López, MG}, title = {Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults--Ineffectiveness of Oral Anticoagulation Treatment with VKA.}, journal = {BioMed research international}, volume = {2015}, number = {}, pages = {134756}, pmid = {26229954}, issn = {2314-6141}, mesh = {Administration, Oral ; Adult ; Aged ; Anticoagulants/administration & dosage/*therapeutic use ; Atrial Fibrillation/*diagnosis/*drug therapy/epidemiology ; Female ; Humans ; Male ; Prevalence ; *Registries ; Risk Factors ; Spain/epidemiology ; Survival Analysis ; Vitamin K/*antagonists & inhibitors ; }, abstract = {OBJECTIVE: This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk.

METHOD: A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were CHA₂DS₂VASC, HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores.

RESULTS: The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a CHA₂DS₂VASC ≥ 2 score; a risk of bleeding in important subgroups using OAC without indication (37.50% CHA₂DS₂VASC < 2 score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score ≥3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range.

CONCLUSIONS: The expected AF prevalence was 10.9% (n 5267), but the registered prevalence was 7.5% (n 3638). Only 35.04% (CI = 95%, 33.7-36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%.}, } @article {pmid26228625, year = {2015}, author = {Picillo, M and Dubbioso, R and Iodice, R and Iavarone, A and Pisciotta, C and Spina, E and Santoro, L and Barone, P and Amboni, M and Manganelli, F}, title = {Short-latency afferent inhibition in patients with Parkinson's disease and freezing of gait.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {122}, number = {11}, pages = {1533-1540}, pmid = {26228625}, issn = {1435-1463}, mesh = {Afferent Pathways/*physiopathology ; Aged ; Electric Stimulation/methods ; Evoked Potentials, Motor/physiology ; Female ; Fingers/physiopathology ; Gait/*physiology ; Gait Disorders, Neurologic/*physiopathology/psychology ; Humans ; Male ; Median Nerve/physiopathology ; Middle Aged ; Motor Cortex/physiopathology ; Muscle, Skeletal/physiopathology ; Neural Inhibition/*physiology ; Neuropsychological Tests ; Parkinson Disease/*physiopathology/psychology ; Somatosensory Cortex/physiopathology ; Time ; Transcranial Magnetic Stimulation/methods ; }, abstract = {Freezing of gait (FOG) is one of the most common gait disturbances in patients with Parkinson's disease (PD). Recently, a PET study has documented that PD patients with FOG display cholinergic deficits selectively driven by nucleus basalis of Meynert (nbM)-neocortical denervation and not by peduncolopontine nucleus (PPN)-thalamic degeneration. Short-latency afferent inhibition (SAI) is a neurophysiological technique that allows evaluating major cholinergic sources in the central nervous system in vivo. We sought to determine whether central cholinergic circuits, evaluated by means of SAI testing, are impaired in patients with PD with FOG (FOG+) as compared to those without (FOG-). SAI and neuropsychological data were collected in 14 FOG+ and 10 FOG-. SAI was also performed in 11 healthy control subjects. Demographic, clinical, and cognitive data were compared by using non-parametric tests. Parametric tests were used to compare electrophysiological results among groups. FOG+ and FOG- had similar SAI without significant differences with controls (p = 0.207). None of the PD patients had SAI values outside the normal range (>72 %). FOG+ presented poorer executive and visuospatial performances as compared to FOG-. Despite the presence of cognitive deficits, SAI failed to detect any significant decrease of cholinergic activity in FOG+. However, nbM-related cholinergic dysfunction cannot be ruled out. In fact, integrity or even increased activation of PPN-related cholinergic circuits may mask an eventual nbM dysfunction thus resulting in normal SAI findings. Indeed, selective PPN cholinergic neurons sparing maybe a distinctive features of FOG. Alternatively or complementary, FOG pathophysiology is underpinned by non-cholinergic neurotransmitters dysfunction.}, } @article {pmid26215945, year = {2015}, author = {Metzger Filho, O and Giobbie-Hurder, A and Mallon, E and Gusterson, B and Viale, G and Winer, EP and Thürlimann, B and Gelber, RD and Colleoni, M and Ejlertsen, B and Debled, M and Price, KN and Regan, MM and Coates, AS and Goldhirsch, A}, title = {Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {33}, number = {25}, pages = {2772-2779}, pmid = {26215945}, issn = {1527-7755}, support = {U24 CA075362/CA/NCI NIH HHS/United States ; CA-75362/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Aromatase Inhibitors/therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/chemistry/*drug therapy ; Carcinoma, Lobular/chemistry/*drug therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/analysis ; Letrozole ; Middle Aged ; Nitriles/*therapeutic use ; Receptor, ErbB-2/analysis ; Tamoxifen/*therapeutic use ; Treatment Outcome ; Triazoles/*therapeutic use ; }, abstract = {PURPOSE: To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.

PATIENTS AND METHODS: Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling.

RESULTS: The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20).

CONCLUSION: The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma.}, } @article {pmid26214623, year = {2015}, author = {Abu Rabi, Z and Zoranovic, T and Milovanovic, J and Todorovic-Rakovic, N and Nikolic-Vukosavljevic, D}, title = {Breast cancer in postmenopausal patients: Impact of age.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {20}, number = {3}, pages = {723-729}, pmid = {26214623}, issn = {1107-0625}, mesh = {Age Factors ; Aged ; *Aging ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/secondary/*therapy ; Chemotherapy, Adjuvant ; Disease Progression ; Disease-Free Survival ; Estrogen Antagonists/therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; *Postmenopause ; Receptors, Estrogen/analysis/drug effects ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Tamoxifen/therapeutic use ; Time Factors ; Treatment Outcome ; }, abstract = {PURPOSE: We analyzed the significance of age together with other classic prognostic parameters on the course of breast cancer in postmenopausal patients.

METHODS: Our study included 151 postmenopausal patients with primary breast cancer, of which 55% received adjuvant tamoxifen therapy and 45% did not receive any kind of therapy. Probabilities of disease-free interval (DFI) were estimated using the Kaplan-Meier method and were compared by the log-rank test. A p value<0.05 was considered as statistically significant.

RESULTS: In the tamoxifen-treated subgroup, patients with estrogen receptor (ER) or progesterone receptor (PR) concentration≥5 fmol/mg had favorable course of disease (p<0.01, p<0.04), respectively. Patients≥66 years of age had a worse disease course compared to those<66 years. Also, patients≥66 years with pT1 tumors had a worse disease course compared to those<66 years and pT1 tumors. This result was repeated in other groups as well. In pT2 (≥2 cm), ER-positive, PR-positive and invasive ductal carcinoma (IDC) subgroups, patients≥66 years always had a worse disease course compared to patients<66 years. In the untreated subgroup, patients with ER≥52 fmol/mg (p<0.01), tumors≥2 cm (p<0.01), IDC (p<0.01) type or ≥56 years (p<0.04) had statistically more recurrences. Among patients≥56 years, those with ER-positive or pT2 tumors had shorter DFI compared to ER-negative or pT1. Positive correlation between ER, PR and age of patients was also shown in this subgroup (p<0.03, p<0.02).

CONCLUSION: Age of patients, ER and PR are significant prognostic factors in the tamoxifen-treated subgroup. In the untreated subgroup relevant prognostic parameters are age, tumor size, histological type and ER. The above prognostic factors retained their value in the long-term follow up in both the investigated subgroups of patients.}, } @article {pmid26214322, year = {2016}, author = {Rosen, DC and Nakash, O and Alegría, M}, title = {The impact of computer use on therapeutic alliance and continuance in care during the mental health intake.}, journal = {Psychotherapy (Chicago, Ill.)}, volume = {53}, number = {1}, pages = {117-123}, doi = {10.1037/pst0000022}, pmid = {26214322}, issn = {1939-1536}, mesh = {Adolescent ; Adult ; Computers/*statistics & numerical data ; Electronic Health Records/*statistics & numerical data ; Female ; Humans ; Male ; Medical History Taking/*methods ; Mental Disorders/*psychology ; Middle Aged ; Patient Dropouts/psychology/*statistics & numerical data ; *Professional-Patient Relations ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Advances in information technology within clinical practice have rapidly expanded over recent years. Despite the documented benefits of using electronic health records, which often necessitate computer use during the clinical encounter, little is known about the impact of computer use during the mental health visit and its effect on the quality of the therapeutic alliance. We investigated the association between computer use and quality of the working alliance and continuance in care in 104 naturalistic mental health intake sessions. Data were collected from 8 safety-net outpatient clinics in the Northeast offering mental health services to a diverse client population. All intakes were video recorded. Use of computer during the intake session was ascertained directly from the recording of the session (n = 22; 22.15% of intakes). Working alliance was assessed from the session videotapes by independent reliable coders, using the Working Alliance Inventory, Observer Form-bond scale. Therapist computer use was significantly associated with the quality of the observer-rated therapeutic alliance (Coefficient = -6.29, SE = 2.2, p < .01; Cohen's effect size of d = -0.76), and client's continuance in care (Odds ratio = .11, CI = 0.03-0.38; p < .001). The quality of the observer-rated working alliance and client's continuance in care were significantly lower in intakes in which the therapist used a computer during the session. Findings indicate a cautionary call in advancing computer use within the mental health intake, and demonstrate the need for future research to identify the specific behaviors that promote or hinder a strong working alliance within the context of psychotherapy in the technological era.}, } @article {pmid26213588, year = {2015}, author = {Johnson, KC and Koestler, DC and Fleischer, T and Chen, P and Jenson, EG and Marotti, JD and Onega, T and Kristensen, VN and Christensen, BC}, title = {DNA methylation in ductal carcinoma in situ related with future development of invasive breast cancer.}, journal = {Clinical epigenetics}, volume = {7}, number = {1}, pages = {75}, pmid = {26213588}, issn = {1868-7075}, support = {HHSN261201100031C/CA/NCI NIH HHS/United States ; P01 CA154292/CA/NCI NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; U01 CA086082/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis.

RESULTS: We measured DNA methylation using the Illumina HumanMethylation450K array of estrogen-receptor positive DCIS (n = 40) and adjacent-normal (n = 15) tissues from subjects in the New Hampshire Mammography Network longitudinal breast imaging registry. We identified locus-specific methylation differences between DCIS and matched adjacent-normal tissue (95,609 CpGs, Q < 0.05). Among 40 DCIS cases, 13 later developed invasive disease and we identified 641 CpG sites that exhibited differential DNA methylation (P < 0.01 and median |∆β| > 0.1) in these cases compared with age-matched subjects without invasive disease. The set of differentially methylated CpG loci associated with disease progression was enriched in homeobox-containing genes (P = 1.3E-09) and genes involved with limb morphogenesis (P = 1.0E-05). In an independent cohort, a subset of genes with progression-related differential methylation between DCIS and invasive breast cancer were confirmed. Further, the functional relevance of these genes' regulation by methylation was demonstrated in early stage breast cancers from The Cancer Genome Atlas database.

CONCLUSIONS: This work contributes to the understanding of epigenetic alterations that occur in DCIS and illustrates the potential of DNA methylation as markers of DCIS progression.}, } @article {pmid26213338, year = {2016}, author = {Martin-Reyes, R and de la Torre Hernandez, JM and Franco-Pelaez, J and Lopez-Palop, R and Telleria Arrieta, M and Amat Santos, IJ and Carrillo Saez, P and Sanchez-Recalde, A and Sanmartin Pena, JC and Garcia Camarero, T and Brugaletta, S and Gimeno de Carlos, F and Pinero, A and Sorto Sanchez, DC and Frutos, A and Lasa Larraya, G and Navarro, F and Farre, J}, title = {The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict fractional flow reserve without adenosine?) multicenter study.}, journal = {Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions}, volume = {87}, number = {2}, pages = {262-269}, doi = {10.1002/ccd.25983}, pmid = {26213338}, issn = {1522-726X}, mesh = {Adenosine/*administration & dosage ; Aged ; Area Under Curve ; *Arterial Pressure ; Blood Flow Velocity ; *Cardiac Catheterization ; Coronary Angiography ; Coronary Stenosis/*diagnosis/physiopathology ; Coronary Vessels/diagnostic imaging/*physiopathology ; Female ; *Fractional Flow Reserve, Myocardial ; Humans ; Hyperemia/physiopathology ; Infusions, Intra-Arterial ; Male ; Microcirculation ; Middle Aged ; Nitroglycerin/*administration & dosage ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Reproducibility of Results ; Severity of Illness Index ; Spain ; Unnecessary Procedures ; Vasodilator Agents/*administration & dosage ; }, abstract = {OBJECTIVE: Functional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations.

OBJECTIVE: We sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa-NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa.

METHODS: We conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30-70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa-NTG and FFR were measured.

RESULTS: 283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa-NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa-NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84-0.92, P < 0.001) and 0.94 (95% CI: 0.92-0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa-NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa-NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa-NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis.

CONCLUSION: The cutoff value of acute Pd/Pa-NTG > 0.88 has a high NPV meaning adenosine-FFR can be avoided in almost half of lesions.}, } @article {pmid26208902, year = {2015}, author = {Benevides, L and da Fonseca, DM and Donate, PB and Tiezzi, DG and De Carvalho, DD and de Andrade, JM and Martins, GA and Silva, JS}, title = {IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.}, journal = {Cancer research}, volume = {75}, number = {18}, pages = {3788-3799}, pmid = {26208902}, issn = {1538-7445}, support = {R01 AI103542/AI/NIAID NIH HHS/United States ; R21 AI083948/AI/NIAID NIH HHS/United States ; I083948-01//PHS HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/chemistry/immunology/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/immunology/mortality/*secondary ; Chemotaxis, Leukocyte/*physiology ; Cytokines/biosynthesis/genetics/metabolism ; Disease Progression ; Disease-Free Survival ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-17/analysis/antagonists & inhibitors/immunology/*physiology ; Lymphocytes, Tumor-Infiltrating/*immunology/metabolism ; Mammary Neoplasms, Experimental/immunology/pathology ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/analysis/antagonists & inhibitors/immunology/*physiology ; Neutrophils/*immunology/metabolism ; Prognosis ; Th17 Cells/immunology ; }, abstract = {The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.}, } @article {pmid26204115, year = {2015}, author = {Son, SH and Lee, SW and Jeong, SY and Song, BI and Chae, YS and Ahn, BC and Lee, J}, title = {Whole-Body Metabolic Tumor Volume, as Determined by (18)F-FDG PET/CT, as a Prognostic Factor of Outcome for Patients With Breast Cancer Who Have Distant Metastasis.}, journal = {AJR. American journal of roentgenology}, volume = {205}, number = {4}, pages = {878-885}, doi = {10.2214/AJR.14.13906}, pmid = {26204115}, issn = {1546-3141}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Metastasis/*diagnostic imaging ; *Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Risk Factors ; *Tomography, X-Ray Computed ; Tumor Burden ; }, abstract = {OBJECTIVE: This study was performed to evaluate the prognostic relevance of PET parameters measured by (18)F-FDG PET/CT in patients with invasive ductal carcinoma of the breast (IDC) who had distant metastasis at the time of initial diagnosis.

MATERIALS AND METHODS: Forty women with IDC who had distant metastasis at the time of initial diagnosis and who underwent FDG PET/CT before receiving treatment were enrolled in the study. Clinicopathologic parameters and metabolic PET parameters, including the maximum standardized uptake value (SUVmax) of the primary tumor (pSUVmax), the SUVmax of the axillary lymph node (nSUVmax), the highest SUVmax of whole malignant lesions (wSUVmax), the whole-body (WB) metabolic tumor volume (MTV), and WB total lesion glycolysis (TLG), were analyzed to determine their usefulness in predicting overall survival (OS). Univariate and multivariate analyses were performed with the use of Kaplan-Meier and Cox proportional hazards models.

RESULTS: Twenty-one of the 40 patients (52.5%) died during follow-up (mean follow-up, 36.4 months; range, 0.8-71.4 months). Nonsurvivors had a statistically significantly higher mean (± SD) WB MTV than did survivors (424.0 ± 683.9 vs 92.1 ± 96.3 cm(3); p = 0.0430). T category, performance of palliative surgery, presence of visceral metastasis, wSUVmax, WB MTV, and WB TLG were identified by univariate analysis as prognostic factors for OS, whereas age, N category, hormone receptor status, status, triple-negative breast cancer status (defined as a tumor for which estrogen receptor, progesterone receptor, and ERBB2 statuses were all negative), pSUVmax, and nSUVmax were not. Multivariate analysis revealed that only WB MTV independently predicted OS (hazard ratio, 4.10; 95% CI, 1.17-14.31; p = 0.0280).

CONCLUSION: The WB MTV value, as determined by FDG PET/CT performed before treatment, was found to be an independent prognostic factor for OS in patients with IDC who had distant metastasis at the time of initial diagnosis.}, } @article {pmid26202552, year = {2015}, author = {Wong, SM and Freedman, RA and Stamell, E and Sagara, Y and Brock, JE and Desantis, SD and Golshan, M}, title = {Modern Trends in the Surgical Management of Paget's Disease.}, journal = {Annals of surgical oncology}, volume = {22}, number = {10}, pages = {3308-3316}, doi = {10.1245/s10434-015-4664-3}, pmid = {26202552}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/radiotherapy/*surgery ; Carcinoma, Ductal, Breast/pathology/radiotherapy/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/radiotherapy/*surgery ; Cohort Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; *Mastectomy ; Middle Aged ; Neoplasm Staging ; Paget's Disease, Mammary/pathology/radiotherapy/*surgery ; Prognosis ; Radiotherapy, Adjuvant ; SEER Program ; Sentinel Lymph Node Biopsy ; }, abstract = {PURPOSE: We examined the incidence and modern national trends in the management of Paget's disease (PD), including the use of breast-conserving surgery (BCS), mastectomy, axillary surgery, and receipt of radiotherapy.

METHODS: Using surveillance, epidemiology and end results (SEER) data, we identified 2631 patients diagnosed with PD during 2000-2011. Of these patients, 185 (7%) had PD of the nipple only, 953 (36.2%) had PD with ductal carcinoma in situ (PD-DCIS), and 1493 (56.7%) had PD with invasive ductal carcinoma (PD-IDC). Trends in age-adjusted incidence, primary surgery, sentinel lymph node biopsy (SLNB), and axillary lymph node dissection were examined. Multivariable logistic regression was used to evaluate factors associated with receipt of BCS and radiotherapy.

RESULTS: A decrease in the age-adjusted incidence of PD occurred from 2000 to 2011 (-4.3% per year, p < 0.05). The overall rates of mastectomy in the PD only, PD-DCIS, and PD-IDC groups were 47, 69, and 88.9%, respectively. Only in the PD-IDC group did the proportion of patients undergoing BCS increase significantly, from 8.5% in 2000 to 15.7% in 2011 (p = 0.01). Of those who underwent axillary surgery, the proportion of patients undergoing SLNB increased from 2000 to 2011. In adjusted analyses, Paget's subgroup, older age, central tumor location, low/intermediate grade, tumor size <2.0 cm, SEER region, and year of diagnosis after 2006 were significantly associated with receipt of BCS.

CONCLUSIONS: The incidence of Paget's disease has decreased over time while modern trends in local therapy suggest that BCS, SLNB, and adjuvant radiotherapy remain underutilized.}, } @article {pmid26200720, year = {2016}, author = {Keränen, AK and Haapea, M and Rissanen, T}, title = {Ultrasonography as a Guiding Method in Breast Micro-Calcification Vacuum-Assisted Biopsies.}, journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)}, volume = {37}, number = {5}, pages = {497-502}, doi = {10.1055/s-0035-1553256}, pmid = {26200720}, issn = {1438-8782}, abstract = {PURPOSE: To assess the visibility of breast micro-calcifications using ultrasonography (US) and the accuracy and clinical usefulness of vacuum-assisted biopsy (VAB) using US guidance (USVAB) as compared to stereotactic guidance (SVAB).

MATERIALS AND METHODS: The study material comprised 158 retrospectively reviewed micro-calcification cases examined with US before VAB. The pre-biopsy US positivity frequency distributions were calculated, and the sensitivity, specificity and accuracy of VAB determined by comparing VAB histology with the surgical pathology or a 12-month follow-up.

RESULTS: 158 US examinations yielded 80 positive and 78 negative results. US positivity correlated to a large size and a suspicious BI-RADS category of the calcifications. USVAB was performed in 49 cases with 61 % malignant, 12 % high-risk and 27 % benign results. The percentages for the 109 SVAB cases were 40 %, 28 % and 32 %, respectively. Specimen radiography demonstrated calcifications in 48 of the 49 (98 %) USVAB cases and in 107 of the 109 (98 %) SVAB cases. The overall accuracy of VAB was 94 % (USVAB 98 %, SVAB 94 %), the sensitivity was 88 % (USVAB 97 %, SVAB 83 %), and the specificity was 100 %. The higher sensitivity of USVAB was due to an accumulation of atypical hyperplasia diagnoses in the SVAB group. The final diagnosis was invasive ductal carcinoma in 21 US-positive and in 4 US-negative cases.

CONCLUSION: Approximately 50 % of mammographically detected micro-calcifications could be detected with ultrasonography. US was found to be a valuable alternative guidance method for vacuum-assisted biopsy of micro-calcifications with a technical success rate and diagnostic accuracy well comparable to the stereotactic method.}, } @article {pmid26195469, year = {2015}, author = {Yoon, PD and Chalasani, V and Woo, HH}, title = {Systematic review and meta-analysis on management of acute urinary retention.}, journal = {Prostate cancer and prostatic diseases}, volume = {18}, number = {4}, pages = {297-302}, pmid = {26195469}, issn = {1476-5608}, mesh = {5-alpha Reductase Inhibitors/therapeutic use ; Acute Disease ; Adrenergic alpha-1 Receptor Antagonists/therapeutic use ; Disease Management ; Humans ; Male ; Odds Ratio ; Prostatectomy/methods ; Prostatic Hyperplasia/complications ; Treatment Outcome ; Urinary Catheterization/methods ; Urinary Retention/*diagnosis/etiology/*therapy ; }, abstract = {BACKGROUND: Acute urinary retention (AUR) is a common urological emergency. In this article, we review the current literature and present a structured summary in management of AUR.

METHODS: A systematic review was conducted using the keywords 'acute AND retention AND urin*' within the title in search engines including Medline, EMBASE and EBM Review. The obtained literature was manually reviewed by the primary author (PDY) and was further refined by confining the subject to management of AUR. Exclusion criteria included paediatric and female population studies, case reports, reviews, surveys, economical assessment and articles on AUR in prostate cancer and post-operative patients.

RESULTS: Total of 54 articles met our inclusion and exclusion criteria. The trial without catheter (TWOC) post-immediate catheterisation is widely practiced although there remains a significant variability in terms of type and duration of catheterisation required, use of concurrent medical therapy or post-catheterisation management. Our systematic review and subsequent meta-analysis has shown superiority of α1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral catheterisation (indwelling catheter (IDC)) and may provide several advantages. Clean intermittent self-catheterisation may be a safe and useful option for patients with AUR until their definitive management. The overall long-term outcome of in-and-out catheterisation remains promising in selected patients. Surgery is an end point in patients with unsuccessful TWOC as well as in those with significant lower urinary tract symptoms post-successful TWOC.

CONCLUSIONS: We recommend use of α1-adrenergic receptor blockers before TWOC and discourage emergency operative management. Use of SPC over IDC in AUR is debatable. Duration of catheterisation is controversial but <3 days is a safe option in avoiding catheterisation-related complications. Although TURP remains the current gold standard, there has been an emergence of newer operative management utilising laser techniques.}, } @article {pmid26193840, year = {2016}, author = {Lee, A and Woo, J and Park, H and Sung, SH and Seoh, JY and Lim, W and Moon, BI}, title = {The value of cytoplasmic Y-box-binding protein 1 as a prognostic marker for breast cancer in Korean.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {5}, pages = {685-691}, pmid = {26193840}, issn = {1880-4233}, mesh = {Adult ; Asian People ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/*mortality/pathology ; Cytoplasm/metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Y-Box-Binding Protein 1/*metabolism ; }, abstract = {BACKGROUND: The human Y-box-binding protein 1 (YB-1) is a member of the DNA/RNA-binding family of proteins that regulates transcription and translation of genes. Previous studies suggest that YB-1 may have an oncogenic role in various cancers. In this study, we evaluate the prognostic value of cytoplasmic YB-1 with respect to breast cancer.

METHODS: Immunohistochemical staining study was performed with YB-1 using tissue block from 233 patients with invasive ductal carcinoma. Patients were divided into two groups according to expression of cytoplasmic YB-1 in tumor cell (high versus low). The relationship between the expression of YB-1, clinicopathological characteristics and breast cancer prognosis was analyzed.

RESULTS: Hormone receptor negativity, worse histologic and nuclear grade, high tumor stage, lymphovascular invasion and high Ki67 (≥14 %) were related with the increased expression of cytoplasmic YB-1 in tumor cell (p < 0.05). Although there was no significant difference in relapse-free survival (RFS) between the two groups (p = 0.412), difference in overall survival (OS) was statistically significant (p = 0.035). In multivariate analysis for OS, YB-1 was an independent prognostic factor (p = 0.043).

CONCLUSION: This suggests that the increased expression of cytoplasmic YB-1 in tumor cells can be regarded as an independent prognostic factor for breast cancer, related to poor prognostics. Expression of cytoplasmic YB-1 in cancer cell could be used as an independent prognostic marker for predicting OS in breast cancer.}, } @article {pmid26193775, year = {2016}, author = {Aires, L and Silva, G and Martins, C and Marques, E and Lagoa, MJ and Ribeiro, JC and Rêgo, C and Nascimento, H and Pereira, PR and Santos-Silva, A and Belo, L and Mota, J}, title = {Exercise intervention and cardiovascular risk factors in obese children. Comparison between obese youngsters taking part in a physical activity school-based programme with and without individualised diet counselling: the ACORDA project.}, journal = {Annals of human biology}, volume = {43}, number = {3}, pages = {183-190}, doi = {10.3109/03014460.2015.1059889}, pmid = {26193775}, issn = {1464-5033}, mesh = {Adolescent ; Body Composition ; Body Height ; Body Weight ; Cardiovascular Diseases/*epidemiology/*etiology ; Child ; *Counseling ; *Diet ; Exercise/*physiology ; Female ; Humans ; Male ; Obesity/complications/*epidemiology ; Risk Factors ; *Schools ; }, abstract = {AIM: To determine the effects of a school-based exercise intervention programme on cardiovascular risk factors, including body fat (BF), metabolic profile and physical activity (PA) in children with and without individualised dietary counselling approach (IDC and WIDC).

SUBJECTS AND METHODS: Forty-six overweight children from 6-16 years old (25 girls, 54.3%; age = 10.3 ± 2.8) of six schools took part in an 8-month interdisciplinary, school-based intervention programme. All children were engaged in PA classes, but only one group was exposed to individualised counselling. Blood pressure (BP), lipids and lipoproteins, accelerometer-based PA, percentage of body fat (%BF) and trunk fat (%TF) measures were taken before and after intervention. General Linear Model (Repeated Measures ANOVA) adjusted for age, maturation and height change was used to analyse the longitudinal effect of individualised counselling between two evaluations in each group.

RESULTS: Favourable changes were observed for %BF, %TF, systolic BP and total cholesterol in the IDC group. Subjects WIDC only increased light and moderate-vigorous PA. In IDC, significant effects for time * group interactions were found for systolic BP, total cholesterol and LDL-cholesterol, indicating that counselling might add favourable changes in these markers, beyond those explained by PA and growth.

CONCLUSION: School-based interventions can contribute to counteracting obesity in youth, particularly when individualised dietary counselling is provided. Therefore, the link between schools and professional counselling should be strengthened to ensure consolidated changes towards healthy behaviours.}, } @article {pmid26191326, year = {2015}, author = {Zhu, D and Fang, C and Chen, H and Wu, C}, title = {Synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese young female: a rare combination.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {5}, pages = {5952-5954}, pmid = {26191326}, issn = {1936-2625}, mesh = {Biomarkers, Tumor/analysis ; Biopsy ; Bone Marrow Examination ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Chemotherapy, Adjuvant ; China ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism/*pathology/surgery ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/chemistry/*pathology/surgery ; Ultrasonography, Mammary ; }, abstract = {Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in western countries, however, infrequent in Eastern countries. We report on a rare case of synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese female patient. A 47-year-old female patient who presented with right breast lump for three month was admitted to our hospital. An ultrasound scan showed two mass in right breast and axillary swollen lymph node. Then, this patient was given right mastectomy and axillary lymph node dissection. Histology report showed invasive ductal carcinoma of the breast (grade I) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Bone marrow was infiltrated by CLL cell. To the best of our knowledge, this is the first report of a Chinese patient suffering from breast carcinoma and chronic lymphocytic leukemia.}, } @article {pmid26190774, year = {2016}, author = {Roth, G and Kanat-Maymon, Y and Assor, A}, title = {The Role of Unconditional Parental Regard in Autonomy-Supportive Parenting.}, journal = {Journal of personality}, volume = {84}, number = {6}, pages = {716-725}, doi = {10.1111/jopy.12194}, pmid = {26190774}, issn = {1467-6494}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Mother-Child Relations/*psychology ; Parenting/*psychology ; *Personal Autonomy ; Young Adult ; }, abstract = {Two studies explored the role of parents' unconditional positive regard (UCPR) as perceived by adolescents and young adults in promoting the effectiveness of specific parenting practices that may support offspring's academic autonomous motivation. Study 1 tested the hypothesis that UCPR predicts rationale-giving and choice-provision practices and, at the same time, moderates their relations with adolescents' autonomous motivation. Study 2 replicated the association between UCPR and the parental practices, and further explored the role of parents' authenticity as an antecedent of UCPR and parental autonomy support. Study 1 included 125 adolescents and Study 2 considered 128 college-students and their mothers. The offspring reported on their perceptions of their mothers and on their autonomous motivation, and the mothers reported on their sense of authenticity. Both studies found consistent associations between UCPR and parenting practices that may support autonomous motivation. Moreover, Study 1 demonstrated that the rationale giving and choice provision were more strongly related to adolescents' autonomous motivation when adolescents perceived mothers as high on UCPR. Finally, Study 2 demonstrated that mothers' authenticity predicted UCPR, which in turn was related to autonomy-supportive parenting. Findings support the assumption that parents' autonomy-supportive practices are more effective when accompanied by UCPR.}, } @article {pmid26190560, year = {2015}, author = {García-Fernández, A and Lain, JM and Chabrera, C and García Font, M and Fraile, M and Barco, I and Torras, M and Reñe, A and González, S and González, C and Piqueras, M and Veloso, E and Cirera, L and Pessarrodona, A and Giménez, N}, title = {Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival.}, journal = {The breast journal}, volume = {21}, number = {5}, pages = {533-537}, doi = {10.1111/tbj.12455}, pmid = {26190560}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Carcinoma, Lobular/*mortality/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Mastectomy/statistics & numerical data ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Survivors/*statistics & numerical data ; Treatment Outcome ; }, abstract = {Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow-up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re-excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease-free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology.}, } @article {pmid26186164, year = {2015}, author = {Liu, M and Guo, G and Xie, F and Wang, S and Yang, H and Wang, S}, title = {Mammary ductoscopy and follow-up avoid unnecessary duct excision in patients with pathologic nipple discharge.}, journal = {Journal of surgical oncology}, volume = {112}, number = {2}, pages = {139-143}, doi = {10.1002/jso.23972}, pmid = {26186164}, issn = {1096-9098}, mesh = {Adult ; Aged ; Breast Diseases/*diagnosis/pathology/*surgery ; Breast Neoplasms/diagnosis/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/surgery ; China ; Dilatation, Pathologic/diagnosis ; *Endoscopy ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/diagnosis ; Inflammation/diagnosis ; Mammary Glands, Human/*pathology/*surgery ; Middle Aged ; Nipples/*pathology ; Papilloma, Intraductal/diagnosis/surgery ; Patient Selection ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; *Unnecessary Procedures ; }, abstract = {BACKGROUND AND OBJECTIVES: The goal of this study was to evaluate the efficacy of ductoscopy and follow-up for the diagnoses of intraductal lesions and the concomitant advantages of avoiding surgery for patients with pathologic nipple discharge (PND).

METHODS: Two hundred and sixty-six ductoscopies were performed for 238 women. Patients with positive ductoscopies underwent surgery. If no positive lesions were present upon ductoscopy, the women were followed.

RESULTS: Of 266 ductoscopic examinations, 168 (63.2%, 168/266) breasts from 165 patients were found to have positive images. The final histopathological results revealed that 93 patients with intraductal papilloma, 42 with intraductal papillomatosis, 15 with ADH lesions, DCIS in 9 patients, 1 case with invasive ductal carcinoma (IDC), 6 cases with duct ectasia, and 2 cases with inflammation. Seventy-three patients with negative results upon ductoscopy were followed with a median time of 48 months. Twelve patients had PND recurrence and were diagnosed as papilloma or papillomatosis based on pathology after surgery. PND disappeared for 51 patients after ductoscopy, and no recurrence or disease evolvement was founded for them.

CONCLUSION: Ductoscopy and follow-up were advantageous for selecting patients to undergo surgery or surveillance. The recurrence of PND after ductoscopy might be a strong predictor for having intraductal disease.}, } @article {pmid26179699, year = {2016}, author = {Cui, M and Wang, Q and Chen, G}, title = {Serum metabolomics analysis reveals changes in signaling lipids in breast cancer patients.}, journal = {Biomedical chromatography : BMC}, volume = {30}, number = {1}, pages = {42-47}, doi = {10.1002/bmc.3556}, pmid = {26179699}, issn = {1099-0801}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*blood/pathology ; Chromatography, High Pressure Liquid ; Disease Progression ; Female ; Humans ; Lipids/*blood ; Mass Spectrometry ; Metabolomics/*methods ; Middle Aged ; Pilot Projects ; }, abstract = {Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer death among women worldwide. It is a biologically variable disease with different molecular subtypes, risk factors, clinical behaviors and responses to treatment. Better understanding of the molecular changes associated with each subtype is essential for identifying new therapeutic targets and markers for the monitoring of treatment responses. In this pilot study, mass spectrometry-based metabolic profiling was performed to characterize the changes in serum profiles of patients with invasive ductal carcinoma (IDC) - the most common type of breast cancer. Serum samples from 20 IDC patients and 20 age- and gender-matched healthy subjects were analyzed and 15 differentially expressed metabolites were identified. These metabolites are involved in several metabolic pathways such as sphingolipid metabolism, phospholipid metabolism and fatty acid β-oxidation. Among these, two classes of signaling lipids, lysophosphatidylethanolamine and ceramide, may play an important role in IDC development and progression. This study demonstrates metabolic profiling as a promising tool for finding disease biomarkers and our findings provide new directions for further mechanistic studies on the pathology of IDC.}, } @article {pmid26179530, year = {2015}, author = {Morita, S and Onaya, H and Kishi, Y and Hiraoka, N and Arai, Y}, title = {Multiple Intraglandular Metastases in a Patient with Invasive Ductal Carcinoma of the Pancreas.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {54}, number = {14}, pages = {1753-1756}, doi = {10.2169/internalmedicine.54.3819}, pmid = {26179530}, issn = {1349-7235}, mesh = {Carcinoma, Pancreatic Ductal/complications/*diagnosis/pathology/surgery ; Cholangiopancreatography, Endoscopic Retrograde ; Flank Pain/etiology ; Humans ; Jaundice/etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Second Primary/complications/*diagnosis/pathology/surgery ; Pancreas/*pathology ; Pancreatectomy/methods ; Pancreatic Neoplasms/complications/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {A 56-year-old man was admitted to our hospital for an evaluation of pancreatic lesions. Computed tomography revealed a hypoattenuating tumor in the head of the pancreas, with three other tumors detected in the body and tail. Magnetic resonance imaging showed similar enhancement patterns and signal intensities in all four lesions. The patient underwent total pancreatectomy based on a preoperative diagnosis of multiple invasive ductal carcinomas. Histopathologically, the lesion in the pancreatic head was considered to be the primary lesion, while the others were diagnosed as metastases. This is a rare case of pancreatic cancer with intraglandular metastases. The possibility of this differential diagnosis should thus be considered when imaging shows multiple hypovascular lesions in the pancreas.}, } @article {pmid26178086, year = {2015}, author = {Si, W and Wu, CQ}, title = {Decoherence and energy relaxation in the quantum-classical dynamics for charge transport in organic semiconducting crystals: An instantaneous decoherence correction approach.}, journal = {The Journal of chemical physics}, volume = {143}, number = {2}, pages = {024103}, doi = {10.1063/1.4926534}, pmid = {26178086}, issn = {1089-7690}, abstract = {We explore an instantaneous decoherence correction (IDC) approach for the decoherence and energy relaxation in the quantum-classical dynamics of charge transport in organic semiconducting crystals. These effects, originating from environmental fluctuations, are essential ingredients of the carrier dynamics. The IDC is carried out by measurement-like operations in the adiabatic representation. While decoherence is inherent in the IDC, energy relaxation is taken into account by considering the detailed balance through the introduction of energy-dependent reweighing factors, which could be either Boltzmann (IDC-BM) or Miller-Abrahams (IDC-MA) type. For a non-diagonal electron-phonon coupling model, it is shown that IDC tends to enhance diffusion while energy relaxation weakens this enhancement. As expected, both the IDC-BM and IDC-MA achieve a near-equilibrium distribution at finite temperatures in the diffusion process, while in the Ehrenfest dynamics the electronic system tends to infinite temperature limit. The resulting energy relaxation times with the two kinds of factors lie in different regimes and exhibit different dependences on temperature, decoherence time, and electron-phonon coupling strength, due to different dominant relaxation processes.}, } @article {pmid26176340, year = {2015}, author = {Waaijer, L and Willems, SM and Verkooijen, HM and Buck, DB and van der Pol, CC and van Diest, PJ and Witkamp, AJ}, title = {Impact of preoperative evaluation of tumour grade by core needle biopsy on clinical risk assessment and patient selection for adjuvant systemic treatment in breast cancer.}, journal = {The British journal of surgery}, volume = {102}, number = {9}, pages = {1048-1055}, doi = {10.1002/bjs.9858}, pmid = {26176340}, issn = {1365-2168}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Decision Support Techniques ; Female ; Humans ; *Mastectomy ; Middle Aged ; Neoplasm Grading ; *Patient Selection ; *Preoperative Care ; Retrospective Studies ; Risk Assessment ; }, abstract = {BACKGROUND: Histological characteristics are important when making a decision on adjuvant systemic treatment in breast cancer. Preoperative assessments of core needle biopsy (CNB) specimens are becoming increasingly relevant as novel minimally invasive ablative techniques are introduced, because a surgical specimen is no longer obtained with these methods. The clinical impact of potential underestimation of tumour grade on preoperative CNB on clinical decision-making was evaluated.

METHODS: Histological tumour grade was reassessed on CNB and resection specimens from consecutive invasive ductal carcinomas diagnosed between 2010 and 2013. For each patient, the indication for systemic therapy was assessed, based on either CNB or surgical excision, in combination with clinical characteristics and imaging findings. The clinical impact of discordance between tumour grade on CNB versus the resection specimen was assessed.

RESULTS: The analysis included 213 invasive ductal carcinomas in 199 patients. Discordance in tumour grade between CNB and the resection specimen was observed in 64 (30.0 per cent) of 213 tumours (κ = 0.53, 95 per cent c.i. 0.43 to 0.63). A decision on adjuvant treatment based on CNB would have resulted in overtreatment in seven (3.5 per cent) and undertreatment in three (1.5 per cent) of 199 patients. In the undertreated patients, incorrect omission of adjuvant systemic treatment would have increased the predicted 10-year mortality rate by 2.6-5.2 per cent and 10-year recurrence rate by 8.2-15.3 per cent based on the online risk assessment tool Adjuvant!

CONCLUSION: The substantial discordance in tumour grading between CNB and resection specimens from breast cancer affects the indication for adjuvant therapy in only a small minority of patients with invasive ductal carcinoma. Assessment of tumour grade by CNB is feasible and accurate for the planning of postoperative treatment.}, } @article {pmid26175196, year = {2015}, author = {Campagna, L and Gronau, I and Silveira, LF and Siepel, A and Lovette, IJ}, title = {Distinguishing noise from signal in patterns of genomic divergence in a highly polymorphic avian radiation.}, journal = {Molecular ecology}, volume = {24}, number = {16}, pages = {4238-4251}, doi = {10.1111/mec.13314}, pmid = {26175196}, issn = {1365-294X}, mesh = {Animals ; Bayes Theorem ; Female ; Gene Flow ; Genetic Loci ; *Genetic Speciation ; Genetics, Population ; Genomics ; Male ; Models, Genetic ; Passeriformes/classification/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; South America ; *Sympatry ; }, abstract = {Recently diverged taxa provide the opportunity to search for the genetic basis of the phenotypes that distinguish them. Genomic scans aim to identify loci that are diverged with respect to an otherwise weakly differentiated genetic background. These loci are candidates for being past targets of selection because they behave differently from the rest of the genome that has either not yet differentiated or that may cross species barriers through introgressive hybridization. Here we use a reduced-representation genomic approach to explore divergence among six species of southern capuchino seedeaters, a group of recently radiated sympatric passerine birds in the genus Sporophila. For the first time in these taxa, we discovered a small proportion of markers that appeared differentiated among species. However, when assessing the significance of these signatures of divergence, we found that similar patterns can also be recovered from random grouping of individuals representing different species. A detailed demographic inference indicates that genetic differences among Sporophila species could be the consequence of neutral processes, which include a very large ancestral effective population size that accentuates the effects of incomplete lineage sorting. As these neutral phenomena can generate genomic scan patterns that mimic those of markers involved in speciation and phenotypic differentiation, they highlight the need for caution when ascertaining and interpreting differentiated markers between species, especially when large numbers of markers are surveyed. Our study provides new insights into the demography of the southern capuchino radiation and proposes controls to distinguish signal from noise in similar genomic scans.}, } @article {pmid26170987, year = {2015}, author = {Min, KW and Chae, SW and Kim, DH and DO, SI and Kim, K and Lee, HJ and Sohn, JH and Pyo, JS and Kim, DH and Oh, S and Choi, SH and Park, YL and Park, CH}, title = {Fascin expression predicts an aggressive clinical course in patients with advanced breast cancer.}, journal = {Oncology letters}, volume = {10}, number = {1}, pages = {121-130}, pmid = {26170987}, issn = {1792-1074}, abstract = {Fascin is an actin cross-linking protein, which regulates actin dynamics and filopodia or spike formation, as well as the epithelial-mesenchymal transition, and has been implicated in cell motility. Although, fascin is pivotal in mediating the aggressive behaviour of various types of cancer, its prognostic significance according to tumour stage has yet to be evaluated. Therefore, the present study investigated fascin expression in 194 patients diagnosed with invasive ductal carcinoma of the breast between 2000 and 2005. Fascin protein expression levels were evaluated by immunostaining on a tissue microarray, and the association between fascin expression and various clinicopathological parameters was analysed. Fascin expression was significantly correlated with various clinicopathological parameters, including high histological grade, tumour necrosis, resistance to adjuvant therapy, high expression of p53 and Ki-67 and specific therapeutic markers (oestrogen and progesterone receptor negativity; all P<0.05). Furthermore, univariate and multivariate analyses identified a significant association between fascin expression, and poor disease-free and overall survival, in late-stage breast cancer (all P<0.05). Therefore, fascin may be crucial in predicting aggressive tumour behaviour, particularly in patients with advanced-stage disease that has acquired the properties of migration and invasion.}, } @article {pmid26165857, year = {2015}, author = {Allen, MD and Jones, LJ}, title = {The role of inflammation in progression of breast cancer: Friend or foe? (Review).}, journal = {International journal of oncology}, volume = {47}, number = {3}, pages = {797-805}, doi = {10.3892/ijo.2015.3075}, pmid = {26165857}, issn = {1791-2423}, mesh = {Biomarkers, Tumor/*immunology ; Breast Neoplasms/*drug therapy/immunology/*pathology ; Disease Progression ; Female ; Humans ; Immunotherapy/methods ; Prognosis ; Tumor Microenvironment/drug effects ; }, abstract = {There is a growing interest in the role of the microenvironment in cancer, however, it has been known for over one hundred years that the immune system plays a prominent role in cancer. Recent decades have revealed more and more data on how our own host response to cancer cells can help or hinder progression of the disease. Despite all this work it is surprising how little is known about the role of the immune system in human breast cancer development, as compared to other cancers. Recent successes of PD-1 blockade in treating multiple cancers, and new developments with other immune targets such as CTLA-4 and CSF-1 inhibitors, highlight that it is becoming ever more important that we understand the complexity of the immune and inflammatory systems in the development and progression of breast cancer. With this knowledge it may be possible to not only target therapy but also more accurately predict those patients that truly need it. This review summarises some of the most significant findings for the role of the immune system and inflammatory response in breast cancer progression. Focusing on how the inflammatory microenvironment may be involved in the progression of pre-invasive ductal carcinoma in situ to invasive breast cancer. It will also discuss the use of immune markers as diagnostic and prognostic tools and summarise the state of the art of immune-therapeutics in breast cancer treatment.}, } @article {pmid26163605, year = {2015}, author = {Payandeh, M and Sadeghi, M and Sadeghi, E and Aeinfar, M}, title = {Clinicopathology Figures and Long-term Effects of Tamoxifen Plus Radiation on Survival of Women with Invasive Ductal Carcinoma and Triple Negative Breast Cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {12}, pages = {4863-4867}, doi = {10.7314/apjcp.2015.16.12.4863}, pmid = {26163605}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Carcinoma, Ductal, Breast/*mortality/*secondary/therapy ; Chemoradiotherapy/*mortality ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Survival Rate ; Tamoxifen/*therapeutic use ; Triple Negative Breast Neoplasms/*mortality/*pathology/therapy ; Young Adult ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports.

MATERIALS AND METHODS: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results.

RESULTS: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively.

CONCLUSIONS: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.}, } @article {pmid26158253, year = {2015}, author = {Gkegkes, ID and Iavazzo, C}, title = {Contrast Enhanced Ultrasound (CEU) Using Microbubbles for Sentinel Lymph Node Biopsy in Breast Cancer: a Systematic Review.}, journal = {Acta chirurgica Belgica}, volume = {115}, number = {3}, pages = {212-218}, doi = {10.1080/00015458.2015.11681099}, pmid = {26158253}, issn = {0001-5458}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/diagnostic imaging ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; Humans ; Image Enhancement ; Lymph Nodes/*diagnostic imaging/pathology ; *Microbubbles ; Middle Aged ; Sentinel Lymph Node Biopsy/*methods ; Ultrasonography, Doppler/*methods ; Young Adult ; }, abstract = {BACKGROUND: The concept of sentinel lymph node (SLN) is not new to medical practice especially in breast cancer patients. CEU microbubble technique is an innovative technique which is applied with the same purpose. It utilizes ultrasound contrast agents based on the use of dispersion with sulfur hexafluoride gas. The aim of this review is to examine the clinical evidence on the role of intradermally injected microbubbles as a technique of preoperative identification of SLNs in patients with breast cancer.

METHODS: A systematic search was performed in PubMed (5 October 2014), Scopus (5 October 2014) and Cochrane libraries (5 October 2014).

RESULTS: Five prospective studies were included in the study. The total number of patients included was 727. The age of the included patients ranged from 19 to 93 years old. The median diameter of tumor ranged from 2 to 120 mm. Regarding the histological type, ductal carcinoma in situ was present in 31 patients, invasive ductal carcinoma in 438, invasive lobular carcinoma in 71 and not defined invasive breast tumors in 52 patients. The SLN identification rate ranged from 9.3% to 55.2% and the sensitivity from 61% to 89% while the false negative rate from 6.6% to 39% and the presence of micro/macrometastases from 1.9% to 64.3%.

CONCLUSIONS: CEU microbubble technique is an alternative technique of SLN detection in breast cancer patients. Further studies are necessary to standardize the method and clarify its specificity and sensitivity. Moreover, randomized control trials are suggested in order to compare this technique with the current techniques used for SLN detection.}, } @article {pmid26155294, year = {2015}, author = {Kim, YH and Yoon, HJ and Kim, Y and Kim, BS}, title = {Axillary Lymph Node-to-Primary Tumor Standard Uptake Value Ratio on Preoperative (18)F-FDG PET/CT: A Prognostic Factor for Invasive Ductal Breast Cancer.}, journal = {Journal of breast cancer}, volume = {18}, number = {2}, pages = {173-180}, pmid = {26155294}, issn = {1738-6756}, abstract = {PURPOSE: This study assessed the axillary lymph node (ALN)-to-primary tumor maximum standard uptake value (SUVmax) ratio (ALN/T SUV ratio) in invasive ductal breast cancer (IDC) on preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to determine the effectiveness in predicting recurrence-free survival (RFS).

METHODS: One hundred nineteen IDC patients (mean age, 50.5±10.5 years) with pathologically proven ALN involvement without distant metastasis and preoperative FDG PET/CT were enrolled in the study. SUVmax values of the ALN and primary tumor were obtained on FDG PET/CT, and ALN/T SUV ratio was calculated. Several factors were evaluated for their effectiveness in predicting RFS. These included several parameters on FDG PET/CT as well as several clinicopathological parameters: pathologic tumor/node stage; nuclear and histological grade; hormonal state; status with respect to human epidermal growth factor receptor 2, mindbomb E3 ubiquitin protein ligase 1 (MIB-1), and p53; primary tumor size; and ALN size.

RESULTS: Among 119 patients with breast cancer, 17 patients (14.3%) experienced relapse during follow-up (mean follow-up, 28.4 months). The ALN/T SUV ratio of the group with disease recurrence was higher than that of the group without recurrence (0.97±1.60 and 0.45±0.40, respectively, p=0.005). Univariate analysis showed that the primary tumor SUVmax, ALN SUVmax, ALN/T SUV ratio, ALN status, nuclear and histological grade, estrogen receptor (ER) status, and MIB-1 status were predictors for RFS. Among these variables, ALN/T SUV ratio with hazard ratio of 4.20 (95% confidence interval [CI], 1.74-10.13) and ER status with hazard ratio of 4.33 (95% CI, 1.06-17.71) were predictors for RFS according to multivariate analysis (p=0.002 and p=0.042, respectively).

CONCLUSION: Our study demonstrated that ALN/T SUV ratio together with ER status was an independent factor for predicting relapse in IDC with metastatic ALN. ALN/T SUV ratio on preoperative FDG PET/CT may be a useful marker for selecting IDC patients that need adjunct treatment to prevent recurrence.}, } @article {pmid26154605, year = {2015}, author = {Walker, CG and Solis-Trapala, I and Holzapfel, C and Ambrosini, GL and Fuller, NR and Loos, RJ and Hauner, H and Caterson, ID and Jebb, SA}, title = {Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.}, journal = {PloS one}, volume = {10}, number = {7}, pages = {e0131681}, pmid = {26154605}, issn = {1932-6203}, support = {MC_EX_G0701642/2/MRC_/Medical Research Council/United Kingdom ; P60 DK020541/DK/NIDDK NIH HHS/United States ; G0701642/MRC_/Medical Research Council/United Kingdom ; MC_U105960389/MRC_/Medical Research Council/United Kingdom ; U105960389/MRC_/Medical Research Council/United Kingdom ; P30 DK020541/DK/NIDDK NIH HHS/United States ; }, mesh = {Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*genetics ; Diet ; Dietary Fats/pharmacology ; Female ; *Genetic Predisposition to Disease ; Humans ; *Life Style ; Male ; Markov Chains ; Middle Aged ; *Models, Biological ; Quantitative Trait, Heritable ; Regression Analysis ; Risk Factors ; Weight Loss ; }, abstract = {The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.}, } @article {pmid26153395, year = {2015}, author = {Santangelo, G and Trojano, L and Barone, P and Vitale, C}, title = {Cortical thickness in Parkinsonians with impulse control disorders: A comment.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {30}, number = {9}, pages = {1293}, doi = {10.1002/mds.26262}, pmid = {26153395}, issn = {1531-8257}, mesh = {Cerebral Cortex/*pathology ; Disruptive, Impulse Control, and Conduct Disorders/*complications/*pathology ; Female ; Humans ; Male ; Parkinson Disease/*complications ; }, } @article {pmid26152288, year = {2015}, author = {Dallol, A and Buhmeida, A and Merdad, A and Al-Maghrabi, J and Gari, MA and Abu-Elmagd, MM and Elaimi, A and Assidi, M and Chaudhary, AG and Abuzenadah, AM and Nedjadi, T and Ermiah, E and Alkhayyat, SS and Al-Qahtani, MH}, title = {Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {12}, pages = {9677-9683}, pmid = {26152288}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Line, Tumor ; CpG Islands ; DNA Methylation/genetics ; Epigenesis, Genetic ; Female ; Fibroblast Growth Factors/*biosynthesis/genetics ; Gene Expression Regulation, Neoplastic ; Glucuronidase/*genetics ; Humans ; Klotho Proteins ; Middle Aged ; Promoter Regions, Genetic ; Receptor, Fibroblast Growth Factor, Type 4/*biosynthesis/genetics ; }, abstract = {Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.}, } @article {pmid26143679, year = {2016}, author = {Al-Khalili, R and Wynn, RT and Ha, R}, title = {The Contact Zone: A Common Site of Tumor Recurrence in a Patient Who Underwent Skin-Sparing Mastectomy and Myocutaneous Flap Reconstruction.}, journal = {Current problems in diagnostic radiology}, volume = {45}, number = {3}, pages = {233-234}, doi = {10.1067/j.cpradiol.2015.05.003}, pmid = {26143679}, issn = {1535-6302}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mastectomy/*methods ; Middle Aged ; *Myocutaneous Flap ; Neoplasm Recurrence, Local/*diagnostic imaging ; }, abstract = {Routine magnetic resonance imaging (MRI) screening is not typically warranted in asymptomatic patients with a history of breast cancer and myocutaneous flap reconstruction due to the rare incidence of local tumor recurrence. We present a case of recurrent invasive ductal carcinoma along the contact zone between the transverse rectus abdominis myocutaneous (TRAM) flap and the native breast tissue that was incidentally detected on a routine high-risk screening-MRI of the breast in an asymptomatic patient with a history of breast cancer.}, } @article {pmid26140849, year = {2015}, author = {Groheux, D and Majdoub, M and Tixier, F and Le Rest, CC and Martineau, A and Merlet, P and Espié, M and de Roquancourt, A and Hindié, E and Hatt, M and Visvikis, D}, title = {Do clinical, histological or immunohistochemical primary tumour characteristics translate into different (18)F-FDG PET/CT volumetric and heterogeneity features in stage II/III breast cancer?.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {42}, number = {11}, pages = {1682-1691}, pmid = {26140849}, issn = {1619-7089}, mesh = {Breast Neoplasms/*diagnosis/metabolism/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Immunohistochemistry ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; *Tomography, X-Ray Computed ; *Tumor Burden ; }, abstract = {PURPOSE: The aim of this retrospective study was to determine if some features of baseline (18)F-FDG PET images, including volume and heterogeneity, reflect clinical, histological or immunohistochemical characteristics in patients with stage II or III breast cancer (BC).

METHODS: Included in the present retrospective analysis were 171 prospectively recruited patients with stage II/III BC treated consecutively at Saint-Louis hospital. Primary tumour volumes were semiautomatically delineated on pretreatment (18)F-FDG PET images. The parameters extracted included SUVmax, SUVmean, metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and heterogeneity quantified using the area under the curve of the cumulative histogram and textural features. Associations between clinical/histopathological characteristics and (18)F-FDG PET features were assessed using one-way analysis of variance. Areas under the ROC curves (AUC) were used to quantify the discriminative power of the features significantly associated with clinical/histopathological characteristics.

RESULTS: T3 tumours (>5 cm) exhibited higher textural heterogeneity in (18)F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUVmax and SUVmean. Invasive ductal carcinoma showed higher SUVmax values than invasive lobular carcinoma (p = 0.008) but MATV, TLG and textural features were not discriminative. Grade 3 tumours had higher FDG uptake (AUC 0.779 for SUVmax and 0.694 for TLG), and exhibited slightly higher regional heterogeneity (AUC 0.624). Hormone receptor-negative tumours had higher SUV values than oestrogen receptor-positive (ER-positive) and progesterone receptor-positive tumours, while heterogeneity patterns showed only low-level variation according to hormone receptor expression. HER-2 status was not associated with any of the image features. Finally, SUVmax, SUVmean and TLG significantly differed among the three phenotype subgroups (HER2-positive, triple-negative and ER-positive/HER2-negative BCs), but MATV and heterogeneity metrics were not discriminative.

CONCLUSION: SUV parameters, MATV and textural features showed limited correlations with clinical and histopathological features. The three main BC subgroups differed in terms of SUVs and TLG but not in terms of MATV and heterogeneity. None of the PET-derived metrics offered high discriminative power.}, } @article {pmid26138552, year = {2015}, author = {Cirqueira, MB and Moreira, MA and Soares, LR and Cysneiros, MA and Vilela, MH and Freitas-Junior, R}, title = {Effect of Ki-67 on Immunohistochemical Classification of Luminal A to Luminal B Subtypes of Breast Carcinoma.}, journal = {The breast journal}, volume = {21}, number = {5}, pages = {465-472}, doi = {10.1111/tbj.12441}, pmid = {26138552}, issn = {1524-4741}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*classification/*metabolism/pathology ; Carcinoma/*classification/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry/methods ; Ki-67 Antigen/*metabolism ; Neoplasm Grading ; Neoplasm Staging ; }, abstract = {It has recently been proposed to include an immunohistochemical marker of cell proliferation, Ki-67, as an element with which to classify the molecular subtypes of breast cancer. The objective of this study was to evaluate the effect of the introduction of the Ki-67 marker on the molecular classification of breast cancer by immunohistochemistry. This study was performed on 234 cases of invasive ductal carcinoma of the breast submitted to two immunohistochemical classification panels, one including Ki-67 and the other not. The data obtained with the two classifications were correlated with well-established prognostic factors such as histologic grade, the number of lymph nodes affected and tumor size. The molecular classification without Ki-67 identified: 136 cases of luminal A (58.1%), 19 cases of luminal B (8.1%), 27 cases of human epidermal growth-factor receptor 2 overexpressing (11.5%), 27 cases of basal-like (11.5%), and 25 cases of nonbasal-like triple-negative tumors (10.7%). When Ki-67 was included, this situation changed significantly, with the following cases being identified: 72 cases of luminal A (30.8%) and 83 cases of luminal B tumors (35.5%), resulting in a Kappa score of 0.216. Evaluation of correlations between the luminal A and luminal B tumor subtypes and the selected prognostic factors showed a statistically significant difference only when Ki-67 was included and only with respect to histologic grade (p < 0.001). The new classification with Ki-67 significantly altered the prevalence of the luminal A and luminal B subtypes and improved correlation with the histologic grade.}, } @article {pmid26137243, year = {2015}, author = {Xuan, J and Zhang, Y and Zhang, X and Hu, F}, title = {Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining.}, journal = {Biomedical reports}, volume = {3}, number = {3}, pages = {395-397}, pmid = {26137243}, issn = {2049-9434}, abstract = {Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis.}, } @article {pmid26137149, year = {2015}, author = {Hu, F and Yang, S and Lv, S and Peng, Y and Meng, L and Gou, L and Zhang, X}, title = {Analysis of AC3-33 gene expression in multiple organ cancer and adjacent normal tissue by RNA in situ hybridization.}, journal = {Oncology letters}, volume = {9}, number = {6}, pages = {2795-2798}, pmid = {26137149}, issn = {1792-1074}, abstract = {The AC3-33 gene encodes a secretory protein that can inhibit Elk1 transcriptional activity via the ERK1/2 pathway. In the current study, in situ RNA hybridization was used to detect the AC3-33 gene expression in multiple organ cancer and cancer-adjacent normal tissue. The results showed that the expression level of AC3-33 varies across different tissues. AC3-33 exhibited positive expression in squamous cell carcinoma of the esophagus, adenocarcinoma of the rectum, hepatocellular carcinoma, squamous cell carcinoma (SCC) of the lung, cancer-adjacent normal hepatic tissue, clear cell carcinoma of the kidney, invasive ductal carcinoma of the breast, SCC of the uterine cervix and cancer-adjacent normal kidney tissue. Negative expression of AC3-33 was observed in adenocarcinoma of the stomach and colon, cancer-adjacent normal esophageal tissue, cancer-adjacent normal gastric tissue, cancer-adjacent normal colon tissue, cancer-adjacent normal rectal tissue, serous adenocarcinoma of the ovary and cancer-adjacent normal ovarian tissue. However, the expression of AC3-33 in cancer adjacent normal breast tissue was partially positive. In conclusion, the AC3-33 gene does exhibit positive expression in certain carcinomas, which may indicate that AC3-33 has a significant involvement in the development and progression of these carcinomas.}, } @article {pmid26134558, year = {2016}, author = {Ohashi, R and Matsubara, M and Watarai, Y and Yanagihara, K and Yamashita, K and Tsuchiya, S and Takei, H and Naito, Z}, title = {Diagnostic value of fine needle aspiration and core needle biopsy in special types of breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {4}, pages = {675-683}, doi = {10.1007/s12282-015-0624-9}, pmid = {26134558}, issn = {1880-4233}, mesh = {Adenocarcinoma, Mucinous/diagnosis/pathology ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*methods ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Carcinoma, Lobular/diagnosis/pathology ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Although fine needle aspiration (FNA) biopsy is an established tool to assess breast lesions, there has been a trend toward using core needle biopsy (CNB) instead. The aim of this study was to compare the diagnostic accuracy of FNA and CNB in special types of breast cancer.

METHODS: A retrospective review of diagnostic results of pre-operatively performed FNA or CNB, or a combination of the two, was conducted. The cases include histologically proven invasive ductal carcinoma of no special type (NST n = 159), invasive lobular carcinoma (ILC n = 65), mucinous carcinoma (MUC n = 51), and apocrine carcinoma (APO n = 25).

RESULTS: The absolute diagnostic sensitivity of FNA to detect malignancy in ILC and APO patients was inferior to that of NST patients (p < 0.001 for ILC and APO). Within each cancer type, the sensitivity of CNB was higher than that of FNA in the ILC and APO patients (p < 0.001 and p < 0.05, respectively). As for NST and MUC patients, FNA and CNB had equivalent sensitivity. The sensitivity of FNA alone significantly improved when combined with CNB in NST, ILC and APO patients (p < 0.05, p < 0.001, and p < 0.05, respectively).

CONCLUSIONS: Our results suggest that FNA has less diagnostic accuracy than CNB for ILC and APO; thus, the use of CNB should be encouraged when these types of cancer are clinically suspected or when the initial FNA is inconclusive.}, } @article {pmid26131178, year = {2015}, author = {Zhang, Q and Ma, B and Kang, M}, title = {A retrospective comparative study of clinicopathological features between young and elderly women with breast cancer.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {4}, pages = {5869-5875}, pmid = {26131178}, issn = {1940-5901}, abstract = {OBJECTIVE: This is a retrospective study to compare the clinicopathological features between young and elderly women with breast cancer.

METHODS: Totally 181 young and 186 elderly breast cancer patients were analyzed and compared in respects of the histological subtype, tumor number and size, tumor location, histological grading, UICC-pTNM pathological staging, and lymph node metastasis status.

RESULTS: Our results showed that invasive ductal carcinoma was the most frequent histotype in young and elderly breast cancer patients. The second most frequent histological subtype was intraductal carcinoma in the young group, while the second leading histotype was invasive lobular carcinoma in the elderly group. No significant differences in tumor number and location were observed between the young and elderly groups. The percentage of patients with tumor size T3 (diameter > 5 cm) and the proportion of patients with histological grade III in the young group were significantly higher than the elderly group. For UICC-pTNM pathological staging, patients at stages 0-I and II in the young group were less than, while patients at stage III was more than, in the elderly group. In addition, the axillary lymph node metastasis rate and the numbers of axillary lymph node metastasis were elevated in the young group, compared with the elderly group.

CONCLUSION: Breast cancer in young female patients is associated with increased aggressiveness and potential malignancy. Our findings might contribute to future diagnosis and treatment of breast cancer in young women.}, } @article {pmid26125904, year = {2015}, author = {Ramos, FS and Serino, LT and Carvalho, CM and Lima, RS and Urban, CA and Cavalli, IJ and Ribeiro, EM}, title = {PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {14}, number = {2}, pages = {6960-6967}, doi = {10.4238/2015.June.26.4}, pmid = {26125904}, issn = {1676-5680}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Protein Disulfide-Isomerases/*genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {Changes in the expression of the protein disulfide isomerase genes PDIA3 and PDIA6 may increase endoplasmic reticulum stress, leading to cellular instability and neoplasia. We evaluated the expression of PDIA3 and PDIA6 in invasive ductal carcinomas. Using reverse transcription-quantitative polymerase chain reaction, we compared the mRNA expression level in 45 samples of invasive ductal carcinoma with that in normal breast samples. Increased expression of the PDIA3 gene in carcinomas (P = 0.0009) was observed. In addition, PDIA3 expression was increased in tumors with lymph node metastasis (P = 0.009) and with grade III (P < 0.02). The PDIA6 gene showed higher expression levels in the presence of lymph node metastasis (U = 99.00, P = 0.0476) and lower expression for negative hormone receptors status (P = 0.0351). Our results suggest that alterations in PDIA3/6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness.}, } @article {pmid26125737, year = {2015}, author = {Zhao, LH and Liu, HG}, title = {Immunohistochemical detection and clinicopathological significance of JARID1B/KDM5B and P16 expression in invasive ductal carcinoma of the breast.}, journal = {Genetics and molecular research : GMR}, volume = {14}, number = {2}, pages = {5417-5426}, doi = {10.4238/2015.May.22.11}, pmid = {26125737}, issn = {1676-5680}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Staging ; Nuclear Proteins/*biosynthesis/genetics ; Repressor Proteins/*biosynthesis/genetics ; }, abstract = {The aims of this study were to investigate the expression of the H3K4 demethylase, jumonji AT-rich interactive domain 1B (JARID1B/KDM5B) and of p16 (multiple tumor suppressor gene MTS1) in breast cancer tissue and determine its clinicopathological significance. JARID1B/KDM5B and P16 protein expression in 176 resected breast cancer specimens and adjacent normal breast tissue was detected by the streptavidin-peroxidase (S-P) immunohistochemical method. The TNM staging grade was assigned according to the World Health Organization (2012) breast classification system. The positive staining rate of JARID1B/KDM5B and p16 protein in cancer tissue was 74.43 and 35.8%, respectively. JARID1B/KDM5B protein expression was positively associated with T grade, Bloom and Richardson (B&R) score and axillary lymph node metastasis (P < 0.05). p16 protein expression was negatively associated with T grade, B&R score, and axillary lymph node metastasis (P < 0.05). JARID1B/KDM5B and p16 protein expression in breast cancer and adjacent normal breast tissue were negatively correlated (r = -0.303, P < 0.001). The data demonstrated that protein expression of p16 and JARID1B/KDM5B is negatively correlated in invasive ductal carcinoma of the breast.}, } @article {pmid26124343, year = {2015}, author = {Grzegrzolka, J and Biala, M and Wojtyra, P and Kobierzycki, C and Olbromski, M and Gomulkiewicz, A and Piotrowska, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P}, title = {Expression of EMT Markers SLUG and TWIST in Breast Cancer.}, journal = {Anticancer research}, volume = {35}, number = {7}, pages = {3961-3968}, pmid = {26124343}, issn = {1791-7530}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression/genetics ; Humans ; Middle Aged ; Nuclear Proteins/*genetics ; RNA, Messenger/genetics ; Snail Family Transcription Factors ; Stromal Cells/metabolism ; Transcription Factors/*genetics ; Twist-Related Protein 1/*genetics ; }, abstract = {BACKGROUND: The epithelial-mesenchymal transition (EMT) has been observed in progression of in situ breast cancer to the invasive form and might be initiated by snail family zinc finger 2 (SLUG) and twist family bHLH transcription factor 1 (TWIST) protein overexpression. During this phenomenon, cells lose their epithelial phenotype and acquire mesenchymal features. The aim of the study was to examine the association of EMT markers SLUG and TWIST with clinicopathological data and the possibility of using these proteins as prognostic markers of breast cancer.

MATERIALS AND METHODS: Immunohistochemical analysis (IHC) of SLUG and TWIST expression was performed on archival paraffin samples of 19 cases with fibrocystic breast changes (control group), 148 cases of invasive ductal breast cancer (IDC) and 26 of invasive lobular breast cancer (ILC). Laser capture microdissection for isolation of cells from 17 frozen samples of IDC was employed and subsequently SLUG and TWIST mRNA expression in cancer and stromal cells was detected separately by real-time polymerase chain reaction.

RESULTS: SLUG and TWIST expression in IDC was significant higher in stromal cells regardless of the method of quantification used (p<0.001 for SLUG mRNA, and p<0.0001 for SLUG IHC, TWIST IHC and TWIST mRNA expression). Positive correlation of SLUG and TWIST protein and mRNA expression was observed in stromal cells of IDC (r=0.347; p<0.0001 and r=0.704; p<0.01, respectively). Expression of TWIST protein in IDC was higher in cancer cells of cases with shorter event-free survival period, as well as in stromal cells of cases with shorter overall survival period (p<0.05 for both).

CONCLUSION: Stromal cells could play a role in the regulation of EMT in breast cancer.}, } @article {pmid26119994, year = {2015}, author = {Karbiener, M and Glantschnig, C and Pisani, DF and Laurencikiene, J and Dahlman, I and Herzig, S and Amri, EZ and Scheideler, M}, title = {Mesoderm-specific transcript (MEST) is a negative regulator of human adipocyte differentiation.}, journal = {International journal of obesity (2005)}, volume = {39}, number = {12}, pages = {1733-1741}, pmid = {26119994}, issn = {1476-5497}, support = {P 25729/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adipocytes/*cytology/physiology ; Adipose Tissue, White/*cytology ; Cell Culture Techniques ; Cell Differentiation ; Gene Expression Regulation ; Humans ; Multipotent Stem Cells/cytology/metabolism ; Obesity/*metabolism ; Proteins/*metabolism ; RNA, Messenger/*metabolism ; }, abstract = {BACKGROUND: A growing body of evidence suggests that many downstream pathologies of obesity are amplified or even initiated by molecular changes within the white adipose tissue (WAT). Such changes are the result of an excessive expansion of individual white adipocytes and could potentially be ameliorated via an increase in de novo adipocyte recruitment (adipogenesis). Mesoderm-specific transcript (MEST) is a protein with a putative yet unidentified enzymatic function and has previously been shown to correlate with adiposity and adipocyte size in mouse.

OBJECTIVES: This study analysed WAT samples and employed a cell model of adipogenesis to characterise MEST expression and function in human.

METHODS AND RESULTS: MEST mRNA and protein levels increased during adipocyte differentiation of human multipotent adipose-derived stem cells. Further, obese individuals displayed significantly higher MEST levels in WAT compared with normal-weight subjects, and MEST was significantly correlated with adipocyte volume. In striking contrast to previous mouse studies, knockdown of MEST enhanced human adipocyte differentiation, most likely via a significant promotion of peroxisome proliferator-activated receptor signalling, glycolysis and fatty acid biosynthesis pathways at early stages. Correspondingly, overexpression of MEST impaired adipogenesis. We further found that silencing of MEST fully substitutes for the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) as an inducer of adipogenesis. Accordingly, phosphorylation of the pro-adipogenic transcription factors cyclic AMP responsive element binding protein (CREB) and activating transcription factor 1 (ATF1) were highly increased on MEST knockdown.

CONCLUSIONS: Although we found a similar association between MEST and adiposity as previously described for mouse, our functional analyses suggest that MEST acts as an inhibitor of human adipogenesis, contrary to previous murine studies. We have further established a novel link between MEST and CREB/ATF1 that could be of general relevance in regulation of metabolism, in particular obesity-associated diseases.}, } @article {pmid26115045, year = {2015}, author = {Zhang, Y and Lv, F and Yang, Y and Qian, X and Lang, R and Fan, Y and Liu, F and Li, Y and Li, S and Shen, B and Pringle, GA and Zhang, X and Fu, L and Guo, X}, title = {Clinicopathological Features and Prognosis of Metaplastic Breast Carcinoma: Experience of a Major Chinese Cancer Center.}, journal = {PloS one}, volume = {10}, number = {6}, pages = {e0131409}, pmid = {26115045}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; China/epidemiology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis/epidemiology/pathology ; Prognosis ; Retrospective Studies ; }, abstract = {Metaplastic breast carcinoma (MBC) is a rare heterogeneous group of primary breast malignancies, with low hormone receptor expression and poor outcomes. To date, no prognostic markers for this tumor have been validated. The current study was undertaken to evaluate the clinicopathologic characteristics, the response to various therapeutic regimens and the prognosis of MBCs in a large cohort of patients from Tianjin Medical University Cancer Hospital in China. Ninety cases of MBCs diagnosed in our hospital between January 2000 and September 2014 were retrieved from the archives. In general, MBCs presented with larger size, a lower rate of lymph node metastasis, and demonstrated more frequent local recurrence/distant metastasis than 1,090 stage-matched cases of invasive carcinoma of no specific type (IDC-NST), independent of the status of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expressions. The five-year disease-free survival (DFS) of MBC was significantly worse than IDC-NST. Using univariate analysis, lymph node metastasis, advanced clinical stage at diagnosis, high tumor proliferation rate assessed by Ki-67 labeling, and epidermal growth factor receptor (EGFR) overexpression/gene amplification were associated significantly with reduced DFS, while decreased OS was associated significantly with lymph node metastasis and EGFR overexpression/gene amplification. With multivariate analysis, lymph node status was an independent predictor for DFS, and lymph node status and EGFR overexpression/gene amplification were independent predictors for OS. Histologic subtyping and molecular subgrouping of MBCs were not significant factors in prognosis. We also found that MBCs were insensitive to neoadjuvant chemotherapy, routine chemotherapy, and radiation therapy. This study indicates that MBC is an aggressive type of breast cancer with poor prognosis, and that identification and optimization of an effective comprehensive therapeutic regimen is needed.}, } @article {pmid26112049, year = {2015}, author = {Romaniuk, A and Lуndіn, M}, title = {Immune microenvironment as a factor of breast cancer progression.}, journal = {Diagnostic pathology}, volume = {10}, number = {}, pages = {79}, pmid = {26112049}, issn = {1746-1596}, mesh = {B-Lymphocytes/*immunology/pathology ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*immunology/pathology ; Carcinoma, Ductal, Breast/chemistry/*immunology/pathology ; Estrogen Receptor alpha/analysis ; Female ; HSP90 Heat-Shock Proteins/analysis ; Humans ; Immunohistochemistry ; Inflammation/*immunology/metabolism/pathology ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Progesterone/analysis ; Triple Negative Breast Neoplasms/chemistry/immunology/pathology ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: The rate of progression of the disease depends on various factors and the tumor microenvironment takes not the last place among them. One part of researchers argues that the presence of tumor-infiltrating leukocytes serves as a favorable marker of the disease. There exists a completely different point of view on the matter. The investigation of the effects of the inflammatory infiltration on the course of breast cancer process.

METHODS: We found a pronounced inflammatory infiltration in the tumor microenvironment in 24 cases. Nineteen cases of IDC without inflammatory infiltration were used as a control group. Immunohistochemical reaction showed expression of ERα, PR, HER2/neu, E-cadherin, Hsp90α, Bcl-2, CD3, CD79α, S100 and Myeloperoxidase receptors. Mathematical calculations were done using Microsoft Excel 2010 with 12.0.5 Attestat option.

RESULTS: We have determined five variants of immune microenvironment: interstitial, trabecular, nodular, diffuse and mixed. We have established a direct correlation between the expression of ERα and PR and indirect correlation between the receptors of steroid hormones and HER2/neo in both groups of breast cancer. HER2/neo positive tumors in 100% of cases were accompanied by the presence of heat shock proteins. There was a combination of Bcl-2 presence with the steroid receptors expression in 90 % of cases. There was found the indirect correlation between the presence of B lymphocytes and expression of steroid receptors.

CONCLUSIONS: The presence of B lymphocytes in an inflammatory infiltrate leads to the disappearance of estrogen receptors and progesterone receptors. It provokes the accumulation of Hsp90 in a cell. It contributes to the stabilization of HER2/neu receptors and most proteins that promote tumor progression.

VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1362330168161694.}, } @article {pmid26110142, year = {2014}, author = {Nasli-Esfahani, E and Peimani, M and Rambod, C and Omidvar, M and Larijani, B}, title = {Developing a Clinical Diabetes Guideline in Diabetes Research Network in Iran.}, journal = {Iranian journal of public health}, volume = {43}, number = {6}, pages = {713-721}, pmid = {26110142}, issn = {2251-6085}, abstract = {Development of evidence-based clinical guidelines to raising standards of medical care in diabetes is a core element of coping with the global diabetes epidemic. The purpose of this study was to develop a systematic clinical diabetes guideline from the latest scientific evidences and also to localize its recommendations according to regional and cultural needs of our society. Searches were conducted using NICE, SIGN, WDPCP, IDF, JDC, ADA, AACE, ICSI, CDA, AMDA, IDC, NyDoH guidelines which were examined and criticized and scored using Agree method. Guidelines which got higher score in some important areas of Agree scale including: rigor of development, clarity and comprehensiveness of the recommendations and applicability, especially in the climatic conditions of our country were selected. The existing recommendations were extracted by committee members and supporting evidences of each recommendation were determined based on the sources listed in the clinical guideline. Recommendations grading were classified from grade A to D based on the quality of their supporting evidences (BEL1-5). This guideline covered all areas related to diabetes including screening and diagnosis, lifestyle modification and patient education, management, complications and hypoglycemia. Regarding capacities of this guideline and lack of comprehensive and updated guidelines in our country and region, it is suggested that designing a pilot study to implement this Learner-centered guideline and finding its weaknesses can lead to patient care improvement and also propel us towards our goal to design a comprehensive guideline in compliance with regional and national needs in Middle East.}, } @article {pmid26101474, year = {2015}, author = {Sikandar, B and Qureshi, MA and Mirza, T and Khan, S and Avesi, L}, title = {Differential immune cell densities in ductal carcinoma In-Situ and invasive breast cancer: Possible role of leukocytes in early stages of carcinogenesis.}, journal = {Pakistan journal of medical sciences}, volume = {31}, number = {2}, pages = {274-279}, pmid = {26101474}, issn = {1682-024X}, abstract = {OBJECTIVES: To investigate immune cell densities in pre-neoplastic (DCIS), cancer (IDC) and control breast tissues.

METHODS: A total of four preneoplastic, 104 cancer and 104 control samples were analyzed. Morphological classification and prognostic scoring along with quantification of immune cells/mm(2) was performed. Data were entered and analyzed using SPSS version 16. Correlation of immune cell densities with various tumour sub-types was investigated using paired t-test and ANOVA. A p-value of <0.05 was considered as significant.

RESULTS: Our data show increased infiltration of lymphocytes (mean lymphocytes = 287.6cells/mm(2)) as well as myelocytes (mean lymphocytes = 117.1cells/mm(2)) in pre-neoplastic tissues. This infiltration was significantly high compared to cancer (p-value<0.001) as well as control tissues (p-value <0.001). Moreover, we report increased infiltration of lymphocytes in cancer tissues compared to controls (p-value<0.001). There was no difference in lymphocyte densities within various tumour sub-types (all p-values >0.05).

CONCLUSION: Leukocytes may play a role in early stages of breast carcinogenesis.}, } @article {pmid26097589, year = {2015}, author = {Lv, ZD and Zhang, L and Liu, XP and Jin, LY and Dong, Q and Li, FN and Wang, HB and Kong, B}, title = {NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {8}, number = {4}, pages = {4015-4021}, pmid = {26097589}, issn = {1936-2625}, support = {CDP 13-005/HX/HSRD VA/United States ; }, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Calcium-Binding Proteins ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/therapy ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; *Cell Movement ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Risk Factors ; Time Factors ; Transfection ; Treatment Outcome ; Young Adult ; }, abstract = {As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.}, } @article {pmid26095656, year = {2015}, author = {Apisarnthanarak, A and Lapcharoen, P and Vanichkul, P and Srisaeng-Ngoen, T and Mundy, LM}, title = {Design and analysis of a pharmacist-enhanced antimicrobial stewardship program in Thailand.}, journal = {American journal of infection control}, volume = {43}, number = {9}, pages = {956-959}, doi = {10.1016/j.ajic.2015.05.011}, pmid = {26095656}, issn = {1527-3296}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; *Antimicrobial Stewardship ; Cohort Studies ; Communicable Diseases/*drug therapy ; Feasibility Studies ; Female ; Hospitalization ; Hospitals, University ; Humans ; Length of Stay ; Male ; Middle Aged ; *Pharmacists ; Professional Role ; Program Development ; Program Evaluation ; Referral and Consultation ; Thailand ; }, abstract = {BACKGROUND: The purpose of this study was to design and evaluate the enhancement of an antibiotic stewardship program (ASP) with trained hospital-based infectious diseases clinical pharmacists (IDCPs).

METHODS: The IDCP training entailed a 12-hour course by 3 pharmacists. From January 1, 2012-September 30, 2012, all patients consecutively admitted with presumptive infections to 6 medicine units were prospectively followed to discharge. Standard of care (SoC) included ASP measures with or without infectious diseases consultations (IDCs). Physician teams had the option to request IDCs, IDCPs, or both. The IDCP support included pharmacist participation in daily rounds to inform on antibiotic use. Outcomes examined were inappropriate antibiotic use, antibiotic de-escalation, duration of antibiotic use, and hospital length of stay (LOS) stratified by patient groups who received SoC versus adjunctive IDCPs with and without IDCs.

RESULTS: There were 150 patients in the SoC group, 104 in the IDCP group, and 320 in the IDCP plus IDC group. Most antibiotic prescriptions were for empirical therapy (n = 373, 65%), and the top-ranked indications were infections of the respiratory tract (n = 287, 50%) and urinary tract (n = 165, 29%). By multivariate analysis, compared with SoC, the 2 other groups were less likely to be prescribed inappropriate antibiotic use (P < .001), had de-escalation of antibiotics (P < .001), received antibiotics <7 days (P < .001), and had subjects with shorter hospital LOSs (P < .001). There were no group differences in mortality.

CONCLUSION: Our study suggests measurable treatment benefits associated with international IDCP training and the integration of adjunct IDCP services into hospital-based ASPs.}, } @article {pmid26093083, year = {2015}, author = {Zeidan, B and Jackson, TR and Larkin, SE and Cutress, RI and Coulton, GR and Ashton-Key, M and Murray, N and Packham, G and Gorgoulis, V and Garbis, SD and Townsend, PA}, title = {Annexin A3 is a mammary marker and a potential neoplastic breast cell therapeutic target.}, journal = {Oncotarget}, volume = {6}, number = {25}, pages = {21421-21427}, pmid = {26093083}, issn = {1949-2553}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Aged ; Annexin A3/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Epithelium/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; MCF-7 Cells ; Mass Spectrometry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Breast cancers are the most common cancer-affecting women; critically the identification of novel biomarkers for improving early detection, stratification and differentiation from benign tumours is important for the reduction of morbidity and mortality.To identify and functionally characterise potential biomarkers, we used mass spectrometry (MS) to analyse serum samples representing control, benign breast disease (BBD) and invasive breast cancer (IDC) patients. Complementary and multidimensional proteomic approaches were used to identify and validate novel serum markers.Annexin A3 (ANX A3) was found to be differentially expressed amongst different breast pathologies. The diagnostic value of serum ANX A3 was subsequently validated by ELISA in an independent serum set representing the three groups. Here, ANX A3 was significantly upregulated in the benign disease group sera compared with other groups (P < 0.0005).In addition, paired breast tissue immunostaining confirmed that ANX A3 was abundantly expressed in benign and to a lesser extent malignant neoplastic epithelium. Finally, we illustrated ANX A3 expression in cell culture lysates and conditioned media from neoplastic breast cell lines, and its role in neoplastic breast cell migration in vitro.This study confirms the novel role of ANX A3 as a mammary biomarker, regulator and therapeutic target.}, } @article {pmid26092536, year = {2015}, author = {Doron, G and Szepsenwol, O}, title = {Partner-focused obsessions and self-esteem: An experimental investigation.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {49}, number = {Pt B}, pages = {173-179}, doi = {10.1016/j.jbtep.2015.05.007}, pmid = {26092536}, issn = {1873-7943}, mesh = {Adult ; Aged ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Obsessive Behavior/*psychology ; Regression Analysis ; *Self Concept ; Social Behavior ; Young Adult ; }, abstract = {BACKGROUND: Relationship-related obsessive-compulsive phenomena (ROCD) are encountered frequently in the clinic, and involve severe consequences to personal and relational well-being. One common presentation of ROCD involves disabling preoccupation and doubts focusing on intimate partner's flaws (partner-focused obsessions). It was previously suggested that individuals perceiving their partner's failures or flaws as reflecting on their own self-worth may be more sensitive to intrusive thoughts pertaining to their partner's qualities and characteristics. In the current studies, we assessed the link between partner-focused OC symptoms and self-esteem contingent on partner-value.

METHODS: In two studies we assessed the impact of experimentally induced partner-focused intrusions on self-esteem. In Study 1, we assessed individuals' self-esteem after one of three primes: (a) intrusion about one's partner comparing unfavorably with others of the same sex (i.e., alternative partners), (b) intrusion about one's partner comparing unfavorably to oneself, (c) and a neutral prime. In study 2, we tried to replicate Study 1 using a pre-post design and also examine whether favorable intrusions of one's partner would have an opposite effect on self-esteem than unfavorable intrusions.

RESULTS: Compared with the other groups, participants who were primed with intrusions of their partner being unfavorably compared to others reported lower self-esteem, but only if they had high levels of partner-focused symptoms. Favorable intrusions of partner to others did not have a positive effect on self-esteem among individuals with high levels of partner-focused symptoms.

CONCLUSIONS: Partner-value self-sensitivity may be one of the perpetuating mechanisms involved in partner-focused OC phenomena.}, } @article {pmid26080617, year = {2015}, author = {Luo, Y and Tanabe, E and Kitayoshi, M and Nishiguchi, Y and Fujiwara, R and Matsushima, S and Sasaki, T and Sasahira, T and Chihara, Y and Nakae, D and Fujii, K and Ohmori, H and Kuniyasu, H}, title = {Expression of MAS1 in breast cancer.}, journal = {Cancer science}, volume = {106}, number = {9}, pages = {1240-1248}, pmid = {26080617}, issn = {1349-7006}, mesh = {Animals ; Apoptosis/genetics ; Carcinoma, Ductal, Breast/drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cisplatin/pharmacology ; ErbB Receptors/genetics ; Female ; Humans ; Immunohistochemistry/methods ; Lymphatic Metastasis/genetics/pathology ; MCF-7 Cells ; Mice ; Proto-Oncogene Mas ; Proto-Oncogene Proteins/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; }, abstract = {MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. MAS1 induces anti-A-II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast. While benign mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDC, especially in scirrhous IDC. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS1. Using the TNBC cell lines 4T1 and MDA-MB-468, which expresses MAS1, we found that cell growth, anti-apoptotic survival and invasion were suppressed by MAS1 activation with A1-7 treatment and enhanced by MAS1 knockdown. In contrast, synergic effect was found between tamoxifen and A1-7 in a luminal A breast cancer cell line, MCF-7. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.}, } @article {pmid26076803, year = {2015}, author = {Poursadegh Zonouzi, AA and Nejatizadeh, A and Rahmati-Yamchi, M and Fardmanesh, H and Shakerizadeh, S and Poursadegh Zonouzi, A and Nejati-Koshki, K and Shekari, M}, title = {Dysregulated expression of Dicer in invasive ductal breast carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {32}, number = {7}, pages = {203}, pmid = {26076803}, issn = {1559-131X}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; DEAD-box RNA Helicases/*genetics ; Down-Regulation/*genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; MicroRNAs/genetics ; Middle Aged ; Ribonuclease III/*genetics ; }, abstract = {Several lines of evidence suggest that the global down-regulation of the microRNAome (miRNAome) involved in pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global down-regulation of the miRNAome. Dicer is a key enzyme in miRNA processing pathway, and dysregulation of its expression has been suggested as a possible cause of miRNAome alterations observed in various cancers. However, Dicer mRNA expression in invasive ductal breast carcinoma (IDC) has not been investigated in depth. Therefore, this study aimed to evaluate the mRNA expression of Dicer in IDC and also to assess the correlation of its expression with clinicopathological parameters including age, histological grade, tumor size and lymph node metastasis. We investigated the expression of the Dicer in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissue by quantitative real-time PCR using validated reference genes. In addition, the possible impact of clinicopathological characteristics on Dicer expression levels was analyzed. Our results showed that Dicer mRNA expression is down-regulated in slightly more than half (51.43 %) of the tumor specimens when compared to adjacent non-neoplastic tissue. Comparison of the Dicer expression level between tumor and matched adjacent non-neoplastic tissue showed that there is no statistical significant differences between them (P = 0.425). We also found that Dicer mRNA expression in IDC samples was not correlated with clinicopathological features. In conclusion, our findings provide additional evidence to support the hypothesis that Dicer expression down-regulated in breast cancer. This study suggested that the decreased expression of Dicer may be potential underlying mechanism in pathogenesis of IDC.}, } @article {pmid26076065, year = {2015}, author = {Khani, F and Epstein, JI}, title = {Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes.}, journal = {The American journal of surgical pathology}, volume = {39}, number = {10}, pages = {1383-1389}, doi = {10.1097/PAS.0000000000000465}, pmid = {26076065}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/secondary/*surgery ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; *Prostatectomy ; Prostatic Neoplasms/chemistry/*pathology/*surgery ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.}, } @article {pmid26074415, year = {2015}, author = {Dittmar, L and Mohr, E and Kleist, C and Ehser, S and Demirdizen, H and Sandra-Petrescu, F and Hundemer, M and Opelz, G and Terness, P}, title = {Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro.}, journal = {Human immunology}, volume = {76}, number = {7}, pages = {480-487}, doi = {10.1016/j.humimm.2015.06.008}, pmid = {26074415}, issn = {1879-1166}, mesh = {Apoptosis/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects ; Humans ; Immunosuppressive Agents/*pharmacology ; Mitomycin/*pharmacology ; Monocytes/cytology/drug effects/radiation effects ; Myeloid Cells/*drug effects ; T-Lymphocytes/immunology ; }, abstract = {Previous animal studies showed that donor-derived blood cells treated with mitomycin C (MMC) prolong allograft survival when injected into recipients. This model was effective with whole blood, peripheral blood mononuclear cells (PBMC) (monocytes being the active cell subpopulation) or dendritic cells. In view of a potential clinical application, we study now the immunosuppressive properties of human myeloid cells in vitro. Mature dendritic cells (generated from naïve monocytes) or monocytes treated with mitomycin C do not or only weakly inhibit allogeneic T cells in vitro, whereas cells in an early differentiation state between monocytes and DC exert suppressive activity when treated with MMC. In contrast, DC generated from MMC-treated monocytes show the morphology and phenotype of early immature DC (iDC) and suppress T-cell responses. It is known that untreated monocytes injected into a recipient encounter a cytokine milieu which differentiates them to stimulatory DC. In our in vitro experiment MMC-treated monocytes cultured in a DC-maturing milieu transform themselves into suppressive early iDC. This reproduces a process which takes place when administering MMC-monocytes to a recipient. In conclusion, human MMC-DC or MMC-monocytes are not or only weakly suppressive in vitro. When MMC-monocytes are differentiated to DC the resulting cells become suppressive.}, } @article {pmid26071494, year = {2016}, author = {Cho, EY and Ko, ES and Han, BK and Kim, RB and Cho, S and Choi, JS and Hahn, SY}, title = {Shear-wave elastography in invasive ductal carcinoma: correlation between quantitative maximum elasticity value and detailed pathological findings.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {57}, number = {5}, pages = {521-528}, doi = {10.1177/0284185115590287}, pmid = {26071494}, issn = {1600-0455}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; *Elasticity Imaging Techniques ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Further information is needed regarding whether histopathological characteristics affect breast tumor elasticity.

PURPOSE: To determine whether maximum elasticity values vary according to tumor-stroma ratio, dominant stroma type, or presence of fibrosis in invasive breast cancer.

MATERIAL AND METHODS: This study included 71 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) who underwent breast shear-wave elastography (SWE). Maximum elasticity (Emax) values were retrospectively correlated with pathological findings that included tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with Emax.

RESULTS: High histologic grade was significantly correlated with higher Emax (P = 0.042). Estrogen receptor and progesterone receptor expression negatively correlated with high elasticity values (P = 0.013 and P = 0.03, respectively). Breast cancers that exhibited higher cellularity demonstrated a greater level of stiffness that was not statistically significant (ρ = 0.153; P = 0.193). While dominant stroma type and fibrosis did not affect Emax (P = 0.197 and P = 0.598, respectively), lesion size was significantly associated with Emax (ρ = 0.474, P < 0.001). On multivariate analysis, only lesion size was significantly associated with Emax (P < 0.001).

CONCLUSION: The composition of tumors did not affect their Emax.}, } @article {pmid26070712, year = {2015}, author = {Stoy, C and Sundaram, A and Rios Garcia, M and Wang, X and Seibert, O and Zota, A and Wendler, S and Männle, D and Hinz, U and Sticht, C and Muciek, M and Gretz, N and Rose, AJ and Greiner, V and Hofmann, TG and Bauer, A and Hoheisel, J and Berriel Diaz, M and Gaida, MM and Werner, J and Schafmeier, T and Strobel, O and Herzig, S}, title = {Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.}, journal = {EMBO molecular medicine}, volume = {7}, number = {8}, pages = {1048-1062}, pmid = {26070712}, issn = {1757-4684}, mesh = {Animals ; Carcinoma, Pancreatic Ductal/*pathology ; Gene Expression Profiling ; Humans ; Mice ; Pancreatic Neoplasms/*pathology ; Survival Analysis ; Transducin/deficiency/*metabolism ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here, we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and invasiveness, correlating with diminished glucose uptake, glycolytic flux, and oncogenic PI3 kinase signaling which in turn could rescue TBL1 deficiency-dependent phenotypes. TBL1 deficiency both prevented and reversed pancreatic tumor growth, mediated transcriptional PI3 kinase inhibition, and increased chemosensitivity of PDAC cells in vivo. As TBL1 mRNA levels were also found to correlate with PI3 kinase levels and overall survival in a cohort of human PDAC patients, TBL1 was identified as a checkpoint in the malignant behavior of pancreatic cancer and its expression may serve as a novel molecular target in the treatment of human PDAC.}, } @article {pmid26070507, year = {2015}, author = {Jazayeri, SB and Saadat, S and Ramezani, R and Kaviani, A}, title = {Incidence of primary breast cancer in Iran: Ten-year national cancer registry data report.}, journal = {Cancer epidemiology}, volume = {39}, number = {4}, pages = {519-527}, doi = {10.1016/j.canep.2015.04.016}, pmid = {26070507}, issn = {1877-783X}, mesh = {Adult ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/*epidemiology ; Female ; Humans ; Incidence ; Iran/epidemiology ; Male ; Middle Aged ; Registries ; }, abstract = {Breast cancer is the leading type of malignancy and the leading cause of cancer-related deaths in women worldwide. The screening programs and advances in the treatment of patients with breast cancer have led to an increase in overall survival. Cancer registry systems play an important role in providing basic data for research and the monitoring of the cancer status. In this study, the results of the 10-year national cancer registry (NCR) of Iran in breast cancer are reviewed. NCR database records were searched for primary breast cancer records according to ICD-O-3 coding and the cases were reviewed. A total of 52,068 cases were found with the coding of primary breast cancer. Females constituted 97.1% of the cases. Breast cancer was the leading type of cancer in Iranian females, accounting for 24.6% of all cancers. The mean age of the women with breast cancer was 49.6 years (95%CI 49.5-49.6). Most of the cases (95.7%) were registered as having invasive pathologies (behavior code 3). The most common morphology of primary breast cancer was invasive ductal carcinoma (ICD-O 8500/3) followed by invasive lobular carcinoma (ICD-O 8520/3) with relative frequencies of 77.8% and 5.2%, respectively. The average annual crude incidence of primary breast cancer in females was 22.6 (95%CI 22.1-23.1) per 100,000 females, with an age-standardized rate (ASR) of 27.4 (95%CI 22.5-35.9). There were no data on survival, staging or immunohistochemical marker(s) of the breast-cancer-registered cases. The incidence of breast cancer in Iran is lower than in low-middle-income neighboring countries. The NCR data registry of breast cancer is not accurate in monitoring the effect of screening programs or determining the current status of breast cancer in Iran. Screening programs of breast cancer in Iran have failed to enhance the detection of the patients with in situ lesion detection. A quality breast cancer registry and a screening program for breast cancer are both needed.}, } @article {pmid26063655, year = {2015}, author = {Yoon, HJ and Kim, Y and Kim, BS}, title = {Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ.}, journal = {European radiology}, volume = {25}, number = {12}, pages = {3648-3658}, pmid = {26063655}, issn = {1432-1084}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging/*methods ; Positron-Emission Tomography/*methods ; Predictive Value of Tests ; Radiopharmaceuticals/pharmacokinetics ; Young Adult ; }, abstract = {OBJECTIVES: This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS).

METHODS: We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent (18) F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min) and ADC difference (ADC diff) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification.

RESULTS: Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044).

CONCLUSIONS: The intratumoral metabolic heterogeneity of (18) F-FDG PET was the most important predictor of invasive components of DCIS.

KEY POINTS: • Preoperative identification of invasion in DCIS is important for axillary nodal management • Higher SUV max and lower AUC-CSH from FDG PET may indicate invasive components of DCIS • Higher TNR and COV from BSGI may indicate invasive components of DCIS • Lower ADC min and higher ADC diff from DWI may indicate invasive components of DCIS • AUC-CSH, an index of metabolic heterogeneity, is an independent predictor for invasive components.}, } @article {pmid26059404, year = {2015}, author = {Jacobs, C and Ibrahim, MF and Clemons, M and Hutton, B and Simos, D and Caudrelier, JM and Graham, ID and Smith, S and Addison, C and Arnaout, A}, title = {Treatment choices for patients with invasive lobular breast cancer: a doctor survey.}, journal = {Journal of evaluation in clinical practice}, volume = {21}, number = {4}, pages = {740-748}, doi = {10.1111/jep.12379}, pmid = {26059404}, issn = {1365-2753}, mesh = {Breast Neoplasms/pathology/*therapy ; Carcinoma, Lobular/pathology/*therapy ; Evidence-Based Medicine ; Female ; Humans ; Neoplasm Invasiveness ; Practice Patterns, Physicians'/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {Invasive lobular breast cancer (ILC) has distinct features that present challenges for management. We surveyed doctors regarding management approaches, opinions on quality of evidence supporting their practice, and future research needs.

METHODS: An online questionnaire was developed and circulated to breast cancer surgical, radiation and medical oncologists.

RESULTS: The questionnaire was completed by 88/428 doctors (20.6%); 22/56 (39.3%) surgeons, 21/64 (32.8%) radiation oncologists and 45/308 (14.6%) medical oncologists. The majority (65%) of surgeons were comfortable treating ILC patients using the same surgical management as patients with invasive ductal cancers (IDC). Furthermore, 25% would perform a similar surgery but would obtain larger gross margins. There was equipoise for radiation oncologists regarding whether or not ILC was an independent risk factor for local-regional recurrence after either breast-conserving surgery or mastectomy. Of those radiation oncologists who believe ILC is an independent risk factor for recurrence after mastectomy, 44.4% would offer radiation in the absence of usual indications. Medical oncologists approached systemic therapy for ILC patients similarly to those with comparable IDCs. Areas identified as most controversial and requiring future research were preoperative magnetic resonance imaging, radiotherapy post-mastectomy and the responsiveness of ILC to adjuvant chemotherapy compared with endocrine therapy.

CONCLUSIONS: There is a variation in doctors' beliefs, management and opinions regarding the quality of evidence for the management of ILC. Clinical trials specifically assessing the management of ILC are required to guide clinical practice.}, } @article {pmid26057036, year = {2015}, author = {Khan, MR and Kang, SW}, title = {Highly Sensitive Multi-Channel IDC Sensor Array for Low Concentration Taste Detection.}, journal = {Sensors (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {13201-13221}, pmid = {26057036}, issn = {1424-8220}, abstract = {In this study, we designed and developed an interdigitated capacitor (IDC)-based taste sensor array to detect different taste substances. The designed taste sensing array has four IDC sensing elements. The four IDC taste sensing elements of the array are fabricated by incorporating four different types of lipids into the polymer, dioctyl phenylphosphonate (DOPP) and tetrahydrofuran (THF) to make the respective dielectric materials that are individually placed onto an interdigitated electrode (IDE) via spin coating. When the dielectric material of an IDC sensing element comes into contact with a taste substance, its dielectric properties change with the capacitance of the IDC sensing element; this, in turn, changes the voltage across the IDC, as well as the output voltage of each channel of the system. In order to assess the effectiveness of the sensing system, four taste substances, namely sourness (HCl), saltiness (NaCl), sweetness (glucose) and bitterness (quinine-HCl), were tested. The IDC taste sensor array had rapid response and recovery times of about 12.9 s and 13.39 s, respectively, with highly stable response properties. The response property of the proposed IDC taste sensor array was linear, and its correlation coefficient R2 was about 0.9958 over the dynamic range of the taste sensor array as the taste substance concentration was varied from 1 μM to 1 M. The proposed IDC taste sensor array has several other advantages, such as real-time monitoring capabilities, high sensitivity 45.78 mV/decade, good reproducibility with a standard deviation of about 0.029 and compactness, and the circuitry is based on readily available and inexpensive electronic components. The proposed IDC taste sensor array was compared with the potentiometric taste sensor with respect to sensitivity, dynamic range width, linearity and response time. We found that the proposed IDC sensor array has better performance. Finally, principal component analysis (PCA) was applied to discriminate different types of taste of the mixed taste substances.}, } @article {pmid26039396, year = {2014}, author = {Silva, FX and Katz, L and Souza, AS and Amorim, MM}, title = {Mammography in asymptomatic women aged 40-49 years.}, journal = {Revista de saude publica}, volume = {48}, number = {6}, pages = {931-939}, pmid = {26039396}, issn = {1518-8787}, mesh = {Adult ; Biopsy ; Brazil ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Cross-Sectional Studies ; Early Detection of Cancer ; Female ; Humans ; Mammography/*statistics & numerical data ; Mass Screening/*methods ; Middle Aged ; Risk Factors ; }, abstract = {OBJECTIVE To assess findings of mammography of and interventions resulting from breast cancer screening in women aged 40-49 years with no increased risk (typical risk) of breast cancer. METHODS This cross-sectional study evaluated women aged 40-49 years who underwent mammography screening in a mastology reference center in Recife, PE, Northeastern Brazil, between January 2010 and October 2011. Women with breast-related complaints, positive findings in the physical examination, or high risk of breast cancer were excluded. RESULTS The 1,000 mammograms performed were classified into the following Breast Imaging-Reporting and Data System (BI-RADS) categories BI-RADS 0, 232; BI-RADS 1, 294; BI-RADS 2, 294; BI-RADS 3, 16; BI-RADS 4A, 2; BI-RADS 5, 1. There was one case of grade II invasive ductal carcinoma and various interventions, including 469 ultrasound scans, 53 referrals to mastologists, 11 cytological examinations, and 8 biopsies. CONCLUSIONS Mammography screening in women aged 40-49 years with typical risk of breast cancer led to the performance of other interventions. However, it also resulted in increased costs without demonstrable efficacy in decreasing mortality.}, } @article {pmid26033922, year = {2015}, author = {Bochicchio, GV and Hipszer, BR and Magee, MF and Bergenstal, RM and Furnary, AP and Gulino, AM and Higgins, MJ and Simpson, PC and Joseph, JI}, title = {Multicenter Observational Study of the First-Generation Intravenous Blood Glucose Monitoring System in Hospitalized Patients.}, journal = {Journal of diabetes science and technology}, volume = {9}, number = {4}, pages = {739-750}, pmid = {26033922}, issn = {1932-2968}, mesh = {Adult ; Aged ; Automation ; Blood Glucose/*analysis ; Calibration ; Catheterization ; Equipment Design ; Female ; Hospitalization ; Humans ; Infusion Pumps, Implantable ; Infusions, Intravenous/instrumentation/methods ; *Insulin Infusion Systems ; Male ; Middle Aged ; Monitoring, Physiologic/*instrumentation/*methods ; Patient Safety ; Prospective Studies ; Reproducibility of Results ; United States ; }, abstract = {BACKGROUND: Current methods of blood glucose (BG) monitoring and insulin delivery are labor intensive and commonly fail to achieve the desired level of BG control. There is great clinical need in the hospital for a user-friendly bedside device that can automatically monitor the concentration of BG safely, accurately, frequently, and reliably.

METHODS: A 100-patient observation study was conducted at 6 US hospitals to evaluate the first generation of the Intravenous Blood Glucose (IVBG) System (Edwards Lifesciences LLC & Dexcom Inc). Device safety, accuracy, and reliability were assessed. A research nurse sampled blood from a vascular catheter every 4 hours for ≤ 72 hours and BG concentration was measured using the YSI 2300 STAT Plus Analyzer (YSI Life Sciences). The IVBG measurements were compared to YSI measurements to calculate point accuracy.

RESULTS: The IVBG systems logged more than 5500 hours of operation in 100 critical care patients without causing infection or inflammation of a vein. A total of 44135 IVBG measurements were performed in 100 patients with 30231 measurements from the subset of 75 patients used for accuracy analysis. In all, 996 IVBG measurements were time-matched with reference YSI measurements. These pairs had a mean absolute difference (MAD) of 11.61 mg/dl, a mean absolute relative difference (MARD) of 8.23%, 93% met 15/20% accuracy defined by International Organization for Standardization 15197:2003 standard, and 93.2% were in zone A of the Clarke error grid. The IVBG sensors were exposed to more than 200 different medications with no observable effect on accuracy.

CONCLUSIONS: The IVBG system is an automated and user-friendly glucose monitoring system that provides accurate and frequent BG measurements with great potential to improve the safety and efficacy of insulin therapy and BG control in the hospital, potentially leading to improved clinical outcomes.}, } @article {pmid26033668, year = {2015}, author = {Saunderson, RB and Gouliouris, T and Nickerson, EK and Cartwright, EJ and Kidney, A and Aliyu, SH and Brown, NM and Limmathurotsakul, D and Peacock, SJ and Török, ME}, title = {Impact of routine bedside infectious disease consultation on clinical management and outcome of Staphylococcus aureus bacteraemia in adults.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {21}, number = {8}, pages = {779-785}, pmid = {26033668}, issn = {1469-0691}, support = {G1000803/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteremia/*diagnosis/*drug therapy/mortality ; Cohort Studies ; Female ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Referral and Consultation/*statistics & numerical data ; Staphylococcal Infections/*diagnosis/*drug therapy/mortality ; Staphylococcus aureus/*isolation & purification ; Survival Analysis ; Treatment Outcome ; United Kingdom ; Young Adult ; }, abstract = {Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.}, } @article {pmid26030494, year = {2015}, author = {Weinberger, S and Greenbaum, D}, title = {Genetic technology to prevent disabilities: how popular culture informs our understanding of the use of genetics to define and prevent undesirable traits.}, journal = {The American journal of bioethics : AJOB}, volume = {15}, number = {6}, pages = {32-34}, doi = {10.1080/15265161.2015.1028665}, pmid = {26030494}, issn = {1536-0075}, mesh = {*Disabled Persons ; *Genetic Variation ; Humans ; Preimplantation Diagnosis/*ethics ; Prenatal Diagnosis/*ethics ; }, } @article {pmid26030252, year = {2015}, author = {McKinnon, E and Xiao, P}, title = {Metaplastic carcinoma of the breast.}, journal = {Archives of pathology & laboratory medicine}, volume = {139}, number = {6}, pages = {819-822}, doi = {10.5858/arpa.2013-0358-RS}, pmid = {26030252}, issn = {1543-2165}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast/*pathology ; Breast Neoplasms/*diagnosis/surgery/therapy ; Chemoradiotherapy ; Etoposide/administration & dosage ; Female ; Humans ; Ifosfamide/administration & dosage ; Metaplasia/surgery/therapy ; Prognosis ; }, abstract = {Metaplastic carcinoma of the breast is a rare but aggressive type of breast cancer that has been recognized as a unique pathologic entity by the World Health Organization. Morphologically, it is characterized by the differentiation of neoplastic epithelium into squamous cells and/or mesenchymal-looking elements (squamous cells, spindle cells, cartilage or bone, etc). It shares many similarities with invasive ductal carcinoma and benign lesions on mammography, which further complicates the diagnosis. Treatment for metaplastic breast carcinoma is relatively unknown because of the rarity of the disease, but studies suggest that removal of the tumor and adjuvant radiation therapy has the greatest benefit.}, } @article {pmid26029227, year = {2015}, author = {Santos, CS and Roriz, M and Carvalho, SM and Vasconcelos, MW}, title = {Iron partitioning at an early growth stage impacts iron deficiency responses in soybean plants (Glycine max L.).}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {325}, pmid = {26029227}, issn = {1664-462X}, abstract = {Iron (Fe) deficiency chlorosis (IDC) leads to leaf yellowing, stunted growth and drastic yield losses. Plants have been differentiated into 'Fe-efficient' (EF) if they resist to IDC and 'Fe-inefficient' (IN) if they do not, but the reasons for this contrasting efficiency remain elusive. We grew EF and IN soybean plants under Fe deficient and Fe sufficient conditions and evaluated if gene expression and the ability to partition Fe could be related to IDC efficiency. At an early growth stage, Fe-efficiency was associated with higher chlorophyll content, but Fe reductase activity was low under Fe-deficiency for EF and IN plants. The removal of the unifoliate leaves alleviated IDC symptoms, increased shoot:root ratio, and trifoliate leaf area. EF plants were able to translocate Fe to the aboveground plant organs, whereas the IN plants accumulated more Fe in the roots. FRO2-like gene expression was low in the roots; IRT1-like expression was higher in the shoots; and ferritin was highly expressed in the roots of the IN plants. The efficiency trait is linked to Fe partitioning and the up-regulation of Fe-storage related genes could interfere with this key process. This work provides new insights into the importance of mineral partitioning among different plant organs at an early growth stage.}, } @article {pmid26026464, year = {2015}, author = {Di Rosa, M and Tibullo, D and Cambria, D and Distefano, G and Saccone, S and Di Raimondo, F and Malaguarnera, L}, title = {Chitotriosidase Expression during Monocyte-Derived Dendritic Cells Differentiation and Maturation.}, journal = {Inflammation}, volume = {38}, number = {6}, pages = {2082-2091}, pmid = {26026464}, issn = {1573-2576}, mesh = {*Cell Differentiation ; Cells, Cultured ; Cytoplasm/enzymology ; Dendritic Cells/*enzymology/immunology ; Gene Expression Regulation, Enzymologic ; Hexosaminidases/genetics/*metabolism ; Humans ; Monocytes/*enzymology/immunology ; Phenotype ; RNA, Messenger/metabolism ; Signal Transduction ; Time Factors ; }, abstract = {The chitotriosidase (CHIT-1) is a glycosyl hydrolase (GH), which has been found highly expressed in activated macrophages and in different monocyte-derived cell lines such as Kupffer cells and osteoclasts, as well is differently produced in diverse stages of macrophage polarization (M1 and M2). Recent finding suggests that CHIT-1 plays a crucial role in innate and acquired immunity. Dendritic cells (DCs) are a complex group of cells that play a critical role in immune response. The aim of this study was to investigate the presence of CHIT-1 during the differentiation and maturation of DCs. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs). Our results showed, for the first time, that CHIT-1 is expressed during the process of differentiation and maturation of DCs in a time-dependent manner. We found that CHIT1 is evenly distributed in cytoplasm of both the iDCs and mDCs. Additionally, a significantly increased expression of CHIT1 mRNA and protein was observed in mature DCs. These results suggest that CHIT-1 play an important role in the DCs immunoresponse.}, } @article {pmid26024935, year = {2015}, author = {Hoefgen, HR and Merritt, DF}, title = {Invasive Ductal Carcinoma in a 46,XY Partial Androgen Insensitivity Syndrome Patient on Hormone Therapy.}, journal = {Journal of pediatric and adolescent gynecology}, volume = {28}, number = {4}, pages = {e95-7}, doi = {10.1016/j.jpag.2014.08.005}, pmid = {26024935}, issn = {1873-4332}, mesh = {Androgen-Insensitivity Syndrome/blood/*diagnosis/etiology ; Breast Neoplasms/blood/*complications/drug therapy ; Carcinoma, Ductal/blood/*complications/drug therapy ; Female ; Follow-Up Studies ; Hormone Replacement Therapy/*adverse effects ; Humans ; Infant, Newborn ; Male ; }, abstract = {BACKGROUND: The hormonal management of patients with androgen insensitivity can be challenging.

CASE: An illustrative case is presented of a newborn with ambiguous genitalia who was raised female. She was diagnosed as 46,XY Disorder of Sexual Development with partial androgen insensitivity. To induce puberty, conjugated equine estrogens were administered beginning at age 12. At age 13, she instead began taking combined oral contraceptives for maternal concerns about height and continued taking them for social reasons. Invasive ductal carcinoma was diagnosed at age 27, and the patient was treated with chemotherapy, radiation therapy, bilateral mastectomies, and endocrine therapy.

SUMMARY AND CONCLUSION: The current literature is reviewed, and hormonal management and other risks for breast cancer are discussed.}, } @article {pmid26022540, year = {2015}, author = {Chen, JM and Qu, AP and Wang, LW and Yuan, JP and Yang, F and Xiang, QM and Maskey, N and Yang, GF and Liu, J and Li, Y}, title = {New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {10690}, pmid = {26022540}, issn = {2045-2322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology ; Cell Nucleus/*pathology ; Disease-Free Survival ; Eosine Yellowish-(YS)/chemistry ; Female ; Hematoxylin/chemistry ; Humans ; *Image Processing, Computer-Assisted ; Kaplan-Meier Estimate ; Middle Aged ; *Prognosis ; }, abstract = {Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001-1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537-0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177-2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142-2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors.}, } @article {pmid26018597, year = {2015}, author = {Golland, Y and Arzouan, Y and Levit-Binnun, N}, title = {The Mere Co-Presence: Synchronization of Autonomic Signals and Emotional Responses across Co-Present Individuals Not Engaged in Direct Interaction.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0125804}, pmid = {26018597}, issn = {1932-6203}, mesh = {Autonomic Nervous System/physiology ; Emotions/*physiology ; Female ; Humans ; Motion Pictures ; }, abstract = {Existing evidence suggests that in social contexts individuals become coupled in their emotions and behaviors. Furthermore, recent biological studies demonstrate that the physiological signals of interacting individuals become coupled as well, exhibiting temporally synchronized response patterns. However, it is yet unknown whether people can shape each other's responses without the direct, face-to-face interaction. Here we investigated whether the convergence of physiological and emotional states can occur among "merely co-present" individuals, without direct interactional exchanges. To this end, we measured continuous autonomic signals and collected emotional responses of participants who watched emotional movies together, seated side-by-side. We found that the autonomic signals of co-present participants were idiosyncratically synchronized and that the degree of this synchronization was correlated with the convergence of their emotional responses. These findings suggest that moment-to-moment emotional transmissions, resulting in shared emotional experiences, can occur in the absence of direct communication and are mediated by autonomic synchronization.}, } @article {pmid26017877, year = {2015}, author = {Fulga, V and Rudico, L and Balica, AR and Cimpean, AM and Saptefrati, L and Raica, M}, title = {Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {66}, number = {1}, pages = {30-37}, doi = {10.5114/pjp.2015.51150}, pmid = {26017877}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/classification/*pathology ; Carcinoma, Ductal, Breast/*chemistry/classification/*secondary ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Lymph Nodes/*chemistry/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phenotype ; Retrospective Studies ; }, abstract = {In the present study we compared the immunophenotypic subtypes of breast ductal invasive carcinomas with their ipsilateral, axillary lymph node metastasis. The ER (estrogen receptor), PR (progesterone receptor), Her2 (human epidermal growth factor receptor 2), and CK5 (cytokeratin 5) status and the proliferation marker Ki-67 were determined by immunohistochemistry on specimens from 43 women. All selected cases were diagnosed as invasive breast carcinomas, of no special type (NST), G2 grade of differentiation. The most frequently encountered subtype at both sites was luminal B. We determined that tumor profile evaluated by surrogate markers is not stable during the metastatic process. The total rate of shifted cases was 23.26% (10 cases), and the highest rate of shifting (6.98%) was encountered from luminal B/Ki-67 to luminal A subtype. In five cases, the subtype shifted to a poorer one according to prognosis. These data support the hypothesis that breast cancer is a heterogeneous disease, with substantial variability of cellular components within each category, a statement applicable to invasive breast carcinomas of NST type too. The receptor profile of this carcinoma, indicated by surrogate markers, is not stable throughout the metastatic process.}, } @article {pmid26004371, year = {2015}, author = {Chung, YR and Kim, H and Park, SY and Park, IA and Jang, JJ and Choe, JY and Jung, YY and Im, SA and Moon, HG and Lee, KH and Suh, KJ and Kim, TY and Noh, DY and Han, W and Ryu, HS}, title = {Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype.}, journal = {Human pathology}, volume = {46}, number = {7}, pages = {1027-1035}, doi = {10.1016/j.humpath.2015.03.015}, pmid = {26004371}, issn = {1532-8392}, mesh = {Adult ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*enzymology/genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/*secondary ; *Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; RNA Interference ; Retrospective Studies ; Sirtuin 1/genetics/*metabolism ; Tissue Array Analysis ; Transfection ; Triple Negative Breast Neoplasms/enzymology/pathology ; }, abstract = {The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor-positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor-positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy.}, } @article {pmid26002985, year = {2015}, author = {Morales Piato, JR and Aguiar, FN and Mota, BS and Ricci, MD and Dória, MT and Alves-Jales, RD and Messias, AP and Filassi, JR and Baracat, EC}, title = {Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {41}, number = {8}, pages = {986-990}, doi = {10.1016/j.ejso.2015.04.019}, pmid = {26002985}, issn = {1532-2157}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Frozen Sections ; Humans ; Mastectomy, Subcutaneous/methods ; Neoplasm Invasiveness ; Neoplasm Staging/*methods ; Nipples/*pathology ; Predictive Value of Tests ; Prospective Studies ; }, abstract = {INTRODUCTION: In this prospective ex vivo study, we propose a new technique for the intraoperative examination of retroareolar tissue and describe both surgical excision and pathological methods. We performed a nipple-sparing mastectomy simulation in patients selected to total mastectomy, in order to evaluate the accuracy of these new technique.

MATERIALS AND METHODS: A total of 158 total mastectomy specimens from patients affected by ductal carcinoma in situ (n = 15) or invasive ductal carcinoma (stages I, II, or IIIA) (n = 143) were examined. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 μm each) at 200 μm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin and were evaluated. The remainder of each fragment was embedded in paraffin and 4 μm sections were subsequently stained with hematoxylin-eosin and examined.

RESULTS: There were two false-negative (1.3%) and five false-positive (3.1%) findings among the frozen and paraffin sections analyzed. A statistical analysis of the frozen section examinations showed a sensitivity of 92.0%, a specificity of 96.2%, a positive predictive value of 82.1%, a negative predictive value of 98.4%, and an accuracy of 95.4%.

CONCLUSION: The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons.}, } @article {pmid26001552, year = {2018}, author = {Comunale, ME and Sandoval, M and Broussard, T}, title = {An Assessment of Basic Patient Safety Skills in Residents Entering the First Year of Clinical Training.}, journal = {Journal of patient safety}, volume = {14}, number = {2}, pages = {112-114}, doi = {10.1097/PTS.0000000000000179}, pmid = {26001552}, issn = {1549-8425}, mesh = {Clinical Competence/*statistics & numerical data ; Humans ; Internship and Residency/*statistics & numerical data ; *Patient Safety ; }, abstract = {OBJECTIVES: During safety rounds, we observed few residents demonstrating hand hygiene and patient identification as they began their postgraduate clinical training. We assessed baseline performance of these 2 basic safety skills in residents entering the first year of postgraduate clinical training (PGY1).

METHODS: PGY1 residents beginning training on July 1, 2013, and July 1, 2014, at our institution were examined using a simulated scenario testing for hand hygiene and patient identification. Nurse volunteers posed as patients and evaluated each resident using a standardized scoring tool. Residents were observed for the following behaviors when interacting: (1) hand hygiene before or upon entry into the patient's room (HHE); (2) resident introducing himself or herself (INTRO); (3) resident identifying patient (IDNB); (4) resident comparing patient's stated name and date of birth to patient's ID band (IDC); (5) resident explaining procedure to patient (EXP); and (6) resident performing hand hygiene upon exiting patient's room (HHL).

RESULTS: A total of 114 residents were examined. Compliance results were as follows: HHE at 66% (75); INTRO at 96% (110); IDNB at 52% (59); IDC at 42% (48); EXP at 90% (103); and HHL at 58% (66).

CONCLUSIONS: Developing and hardwiring basic patient safety skills is essential for creating an institutional culture of safety. We used a simulated patient scenario to provide a baseline assessment of 2 important safety skills.The results obtained demonstrate poor compliance with hand hygiene and patient identification. Our results suggest that there is a need for additional training and perhaps new methods of training and reinforcement in medical school and beyond, to hardwire these basic patient safety skills.}, } @article {pmid25998492, year = {2015}, author = {Ben-Zvi, S and Soroker, N and Levy, DA}, title = {Parietal lesion effects on cued recall following pair associate learning.}, journal = {Neuropsychologia}, volume = {73}, number = {}, pages = {176-194}, doi = {10.1016/j.neuropsychologia.2015.05.009}, pmid = {25998492}, issn = {1873-3514}, mesh = {Acoustic Stimulation ; Adult ; Aged ; Aged, 80 and over ; Association Learning/*physiology ; Auditory Perception/physiology ; Brain Mapping ; Cues ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mental Recall/*physiology ; Middle Aged ; Neuropsychological Tests ; Parietal Lobe/pathology/physiology/*physiopathology ; Photic Stimulation ; Stroke/pathology/*physiopathology ; Tomography, X-Ray Computed ; Visual Perception/physiology ; Young Adult ; }, abstract = {We investigated the involvement of the posterior parietal cortex in episodic memory in a lesion-effects study of cued recall following pair-associate learning. Groups of patients who had experienced first-incident stroke, generally in middle cerebral artery territory, and exhibited damage that included lateral posterior parietal regions, were tested within an early post-stroke time window. In three experiments, patients and matched healthy comparison groups executed repeated study and cued recall test blocks of pairs of words (Experiment 1), pairs of object pictures (Experiment 2), or pairs of object pictures and environmental sounds (Experiment 3). Patients' brain CT scans were subjected to quantitative analysis of lesion volumes. Behavioral and lesion data were used to compute correlations between area lesion extent and memory deficits, and to conduct voxel-based lesion-symptom mapping. These analyses implicated lateral ventral parietal cortex, especially the angular gyrus, in cued recall deficits, most pronouncedly in the cross-modal picture-sound pairs task, though significant parietal lesion effects were also found in the unimodal word pairs and picture pairs tasks. In contrast to an earlier study in which comparable parietal lesions did not cause deficits in item recognition, these results indicate that lateral posterior parietal areas make a substantive contribution to demanding forms of recollective retrieval as represented by cued recall, especially for complex associative representations.}, } @article {pmid25994431, year = {2015}, author = {Teoh, ZH and Archampong, D and Gate, T}, title = {Breast cancer in male-to-female (MtF) transgender patients: is hormone receptor negativity a feature?.}, journal = {BMJ case reports}, volume = {2015}, number = {}, pages = {}, pmid = {25994431}, issn = {1757-790X}, mesh = {Adult ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Estrogens/*adverse effects ; Female ; Humans ; Male ; Receptors, Estrogen/*analysis ; Sentinel Lymph Node Biopsy ; *Transgender Persons ; }, abstract = {A 41-year-old male-to-female (MtF) transgender patient presented with a symptomatic tender lump in the left breast. There was no family history of breast cancer. She had been receiving estrogen therapy for 14 years to maintain her secondary sexual characteristics. Triple assessment revealed a 13 mm triple-negative grade 3 invasive ductal carcinoma. The tumour was completely excised following a left wide local excision and sentinel lymph node biopsy. There was no regional lymph node involvement. She was referred to the oncologist for adjuvant chemotherapy and radiotherapy.}, } @article {pmid25986061, year = {2015}, author = {Tan, QT and Chuwa, EW and Chew, SH and Lim-Tan, SK and Lim, SH}, title = {Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge.}, journal = {International journal of surgery (London, England)}, volume = {19}, number = {}, pages = {22-26}, doi = {10.1016/j.ijsu.2015.05.010}, pmid = {25986061}, issn = {1743-9159}, mesh = {Adult ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Adenoid Cystic/pathology/surgery ; Carcinoma, Adenosquamous/*pathology/surgery ; Carcinoma, Ductal/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Fibroadenoma/pathology/surgery ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/*pathology/surgery ; Phyllodes Tumor/pathology/surgery ; Prognosis ; Radiotherapy, Adjuvant ; Sentinel Lymph Node Biopsy ; }, abstract = {Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic breast cancer with both glandular as well as squamous differentiation. Their lack of distinct imaging characteristics, sometimes subtle histological characteristics and overlapping features with other benign lesions pose a diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to March 2014. In six cases, LGAC was only found after excisional biopsy. In our patients, LGAC frequently co-existed with other forms of breast pathology. Two patients had incidental findings of LGAC alongside their primary malignant tumour (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between 0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant phyllodes tumour in the other). A further four patients had LGAC within a complex sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had a focus of LGAC within a benign phyllodes tumour. None of the patients had evidence of nodal involvement. A high degree of suspicion is recommended as such lesions tend to be incidental histological findings within benign tumours or within complex sclerosing lesions. Although the risk of nodal and distant metastasis is low, the potential for local recurrence necessitates aggressive local excision with margin clearance. The role of axillary dissection has yet to be defined and routine sentinel node biopsy and axillary clearance may not be necessary in view of rarity of nodal metastasis in literature. Benefit from adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients in our study have shown no evidence of recurrence after definitive surgery but longer periods of surveillance is required.}, } @article {pmid25981591, year = {2015}, author = {Lajus, TB and Sales, RM}, title = {CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer.}, journal = {Gene}, volume = {568}, number = {2}, pages = {215-219}, doi = {10.1016/j.gene.2015.05.035}, pmid = {25981591}, issn = {1879-0038}, mesh = {Adult ; Aged ; Antigens, CD ; Breast Neoplasms/*genetics ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics ; DNA Mutational Analysis ; Female ; Genetic Testing ; Germ-Line Mutation ; Humans ; Male ; Mutation, Missense ; Stomach Neoplasms/*genetics ; }, abstract = {Germ-line mutation in CDH1 gene is associated with high risk for Hereditary Diffuse Gastric Cancer (HDGC) and Infiltrative Lobular Carcinoma (ILC). Although somatic CDH1 mutations were also detected in ILC with a frequency ranging from 10 to 56%, CDH1 alterations in more frequent infiltrative ductal carcinoma (IDC) appear to be rare, and no association with germ-line CDH1 mutation and IDC has been established. Here we report the case of a woman diagnosed with IDC at 39years of age, presenting extensive familial history of cancer at multiple sites with early-age onset and with no case of HDGC. Deep sequencing have revealed CDH1 missense mutation c.1849G>A (p.Ala617Thr) in heterozygous and four BRCA2 single nucleotide polymorphism in homozygosis. In this family, the mutation c.1849G>A in the CDH1 gene is not related to HDGC nor ILC. Therefore, here we highlight that multigene analysis is important to detect germ-line mutations and genetic variants in patients with cancers at multiple sites in the family, even if inconclusive genetic counseling can be offered, since hereafter, medical awareness will be held.}, } @article {pmid25980321, year = {2016}, author = {Truin, W and Vugts, G and Roumen, RM and Maaskant-Braat, AJ and Nieuwenhuijzen, GA and van der Heiden-van der Loo, M and Tjan-Heijnen, VC and Voogd, AC}, title = {Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {23}, number = {1}, pages = {51-57}, pmid = {25980321}, issn = {1534-4681}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/metabolism/secondary/*surgery ; Carcinoma, Lobular/drug therapy/metabolism/secondary/*surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC).

METHODS: Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry.

RESULTS: A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P < 0.0001). Breast-conserving surgery was performed for 24.4 % of the patients with ILC receiving NAC versus 39.4 % of the patients with IDC. In the ILC group, 8.2 % of the patients needed surgical reinterventions after BCS due to tumor-positive resection margins compared with 3.4 % of the patients with IDC (P < 0.0001). Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC.

CONCLUSION: The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.}, } @article {pmid25975907, year = {2015}, author = {Li, M and Bao, L and Cai, H and Yang, H and Ge, W and Ren, L and Lu, B}, title = {[Significance of carbonic anhydrase IX protein in fibrotic foci of mammary invasive ductal carcinomas].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {44}, number = {4}, pages = {250-253}, pmid = {25975907}, issn = {0529-5807}, mesh = {Age Factors ; Antigens, Neoplasm ; Breast Neoplasms/*metabolism/pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Female ; Fibroblasts/metabolism ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Proteins ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {OBJECTIVE: To study the relationship between fibrotic focus (FF) and carbonic anhydrase (CA) IX in invasive ductal carcinomas (IDC) of the breast.

METHODS: In 167 cases of IDC, the FF was assessed morphologically, and expression of ER, PR and CA IX was evaluated using MaxVision immunohistochemistry.

RESULTS: The expression of CA IX in IDC with and without FF was 56.3% (45/80) and 28.7% (25/87) respectively, with significant difference (P=0.001). In IDC with FF, the CA IX expression of tumor cells in tumors with CA IX-positive fibroblasts (35/40, 87.5%) was significantly (P<0.001) higher than that in tumors with CA IX-negative fibroblasts (10/40, 25.0%). In IDC with FF, the CA IX expression of fibroblasts of FF in grade 3 IDC (23/33, 69.7%) was significantly (P=0.006) higher than that in grade 1+2 tumors (17/47, 36.2%). The ER and PR expression of tumor cells in tumors containing CA IX-negative fibroblasts was 72.5% (29/40) and 65.0% (26/40) respectively, whereas the ER and PR expression of tumor cells in tumors containing CA IX-positive fibroblasts was 50.0% (20/40) and 42.5% (17/40) respectively; the difference was statistically significant (for both ER and PR, P=0.04). The age of patients with tumors containing CA IX-negative fibroblasts was significantly (P=0.002) older than those containing CA IX-positive fibroblasts. The FF diameter/tumor diameter in tumors containing CA IX-positive fibroblasts was significantly larger than those containing CA IX-negative fibroblasts. (3) For the groups of tumor size≤2 cm and tumor size between 2 cm to 5 cm, the diameter of the fibrotic focus was significantly (P<0.01) smaller than the fibrotic focus size of tumors>5 cm in size.

CONCLUSIONS: CA IX expression is correlated with FF, and that in fibroblasts of FF correlated with patients' age, tumor grade, hormone receptors and FF diameter/tumor diameter. CA IX expression in FF might be a marker for poor prognosis in patients with breast cancer.}, } @article {pmid25974055, year = {2015}, author = {Drill, R and Nakash, O and DeFife, JA and Westen, D}, title = {Assessment of clinical information: Comparison of the validity of a Structured Clinical Interview (the SCID) and the Clinical Diagnostic Interview.}, journal = {The Journal of nervous and mental disease}, volume = {203}, number = {6}, pages = {459-462}, pmid = {25974055}, issn = {1539-736X}, support = {R01 MH078100/MH/NIMH NIH HHS/United States ; 5R01-MH78100/MH/NIMH NIH HHS/United States ; }, mesh = {Adaptation, Psychological/*physiology ; Adolescent ; Adult ; Aged ; Female ; Humans ; Interview, Psychological/standards ; Male ; Mental Disorders/*diagnosis ; Middle Aged ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*instrumentation ; Reproducibility of Results ; Young Adult ; }, abstract = {Adaptive functioning is a key aspect of psychiatric diagnosis and assessment in research and practice. This study compared adaptive functioning validity ratings from Structured Clinical Interviews (SCIDs, symptom-focused structured diagnostic interviews), and Clinical Diagnostic Interviews (CDIs, systematic diagnostic interviews modeling naturalistic clinical interactions focusing on relational narratives). Two hundred forty-five patients (interviewed by two independent interviewers) and their interviewers completed the Clinical Data Form which assesses adaptive functioning and clinical information. Both interviews converged strongly with patient-reports, with no significant differences in validity of the interviews in measuring global and specific domains of adaptive functioning variables. Findings suggest that CDIs provide adaptive functioning data comparable to SCIDs (often considered "gold standard" for assessment but difficult to use in practice) and have important implications for bridging the research-practice gap. By incorporating clinicians' everyday methods, CDIs yield information that is psychometrically sound for empirical investigation, diagnostically practical, and clinically meaningful and valid.}, } @article {pmid25973175, year = {2015}, author = {Nakash, O and Razon, L and Levav, I}, title = {Primary mental health prevention themes in published research and academic programs in Israel.}, journal = {Israel journal of health policy research}, volume = {4}, number = {}, pages = {3}, pmid = {25973175}, issn = {2045-4015}, abstract = {BACKGROUND: The World Health Organization Comprehensive Mental Health Action Plan (CMHAP) 2013-2020 proposes the implementation of primary prevention strategies to reduce the mental health burden of disease. The extent to which Israeli academic programs and published research adhere to the principles spelled out by the CMHAP is unknown.

OBJECTIVE: To investigate the presence of mental health primary prevention themes in published research and academic programs in Israel.

METHODS: We searched for mental health primary prevention themes in: (1) three major journals of psychiatry and social sciences during the years 2001-2012; (2) university graduate programs in psychology, social work and medicine in leading universities for the academic year of 2011-2012; and (3) doctoral and master's theses approved in psychology and social work departments in five universities between the years 2007-2012. We used a liberal definition of primary prevention to guide the above identification of themes, including those related to theory, methods or research information of direct or indirect application in practice.

RESULTS: Of the 934 articles published in the three journals, 7.2%, n = 67, addressed primary prevention. Of the 899 courses in the 19 graduate programs 5.2%, n = 47, elective courses addressed primary prevention. Of the 1960 approved doctoral and master's theses 6.2%, n = 123, addressed primary prevention. Only 11 (4.7%) articles, 5 (0.6%) courses, and 5 (0.3%) doctoral and master's theses addressed primary prevention directly.

CONCLUSIONS: The psychiatric reform currently implemented in Israel and WHO CMHAP call for novel policies and course of action in all levels of prevention, including primary prevention. Yet, the latter is rarely a component of mental health education and research activities. The baseline we drew could serve to evaluate future progress in the field.}, } @article {pmid25971426, year = {2015}, author = {Dashevsky, BZ and Goldman, DA and Parsons, M and Gönen, M and Corben, AD and Jochelson, MS and Hudis, CA and Morrow, M and Ulaner, GA}, title = {Appearance of untreated bone metastases from breast cancer on FDG PET/CT: importance of histologic subtype.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {42}, number = {11}, pages = {1666-1673}, pmid = {25971426}, issn = {1619-7089}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/*diagnosis/diagnostic imaging/*secondary ; Breast Neoplasms/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; *Multimodal Imaging ; Neoplasm Grading ; *Positron-Emission Tomography ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {PURPOSE: To determine if the histology of a breast malignancy influences the appearance of untreated osseous metastases on FDG PET/CT.

METHODS: This retrospective study was performed under IRB waiver. Our Hospital Information System was screened for breast cancer patients who presented with osseous metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included. Patients with a history of other malignancies were excluded. PET/CT was evaluated, blinded to histology, to classify osseous metastases on a per-patient basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record SUVmax for osseous metastases on PET.

RESULTS: Following screening, 95 patients who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC osseous metastases were more commonly sclerotic and demonstrated lower SUVmax than IDC metastases. In all IDC and MDL patients with osseous metastases, at least one was FDG-avid. For ILC, all patients with lytic or mixed osseous metastases demonstrated at least one FDG-avid metastasis; however, in only three of seven patients were sclerotic osseous metastases apparent on FDG PET.

CONCLUSION: The histologic subtype of breast cancer affects the appearance of untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic osseous metastases were more common in patients with ILC than in patients with IDC. Breast cancer histology should be considered when interpreting non-FDG-avid sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases (rather than benign lesions) in patients with ILC.}, } @article {pmid25969822, year = {2015}, author = {Zain, M and Awan, FR and Amir, S and Baig, SM}, title = {A case control association study of COMT gene polymorphism (I/D) with type 2 diabetes and its related factors in Pakistani Punjabi population.}, journal = {Journal of diabetes and metabolic disorders}, volume = {14}, number = {}, pages = {40}, pmid = {25969822}, issn = {2251-6581}, abstract = {BACKGROUND: The Catechol-O-Methyl Transferase (COMT) gene polymorphism (I/D of C nucleotide at base position 900) has been previously implicated in the development of type 2 diabetes (T2D) and kidney disease. So, aim of this study was to find association of I/D polymorphism with T2D, and its associated factors like family history and nephropathy (End Stage Renal Disease, ESRD) patients in a cohort of Pakistani Punjabis.

METHODS: Genomic DNA was extracted from human subjects divided as four study groups: controls (n = 46), diabetics (n = 46), diabetics with nephropathy/ESRD (n = 53), and non-diabetics without nephropathy/ESRD (n = 43). The 900 I/D C polymorphism in the COMT gene was tested by PCR-RFLP method. Genotype and allele frequencies as well as Odds Ratios were calculated for these groups. Groups were compared statistically for the analysis of genotypes, alleles, biochemical parameters as well as disease status.

RESULTS: In comparison with control group (non-diabetic, non-nephropathy), there was no significant difference in rest of the three groups for allele or genotype frequencies of COMT gene. However, Chi square (χ(2)) analysis identified a significant (p = 0.02) correlation of the 900 I/D C polymorphism with family history of diabetes, as it was found that greater number (74%) of patients having I allele had a positive family history of T2D.

CONCLUSIONS: A significant correlation of the COMT polymorphism (900 I/D C) with the family history of T2D has been observed, which has not been previously reported in Pakistani Punjabi population, however, this preliminary finding requires further validation studies.}, } @article {pmid25966732, year = {2015}, author = {Nwafor, CC and Keshinro, SO}, title = {Pattern of hormone receptors and human epidermal growth factor receptor 2 status in sub-Saharan breast cancer cases: Private practice experience.}, journal = {Nigerian journal of clinical practice}, volume = {18}, number = {4}, pages = {553-558}, doi = {10.4103/1119-3077.156905}, pmid = {25966732}, issn = {1119-3077}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Nigeria/epidemiology ; Prevalence ; *Private Practice ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/epidemiology/*metabolism ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or negative (-). The IHC classification correlates well with intrinsic gene expression microarray categorization. ER-positive tumors may benefit from being treated with selective ER modulators and aromatase inhibitors, whereas patients with HER2/neu positive tumors have been shown to experience a significant survival advantage when treated with humanized monoclonal antibodies against HER2/neu.

OBJECTIVE: To determine ER/PR, HER2/neu expression and their association with histological prognostic markers in female breast carcinomas seen in a private diagnostic laboratory based in Lagos.

MATERIALS AND METHODS: Immunohistochemistry reports of breast cancer patients, which were diagnosed by histopathology section of a private diagnostic laboratory based in Lagos, Nigeria from August 2009 to August 2014.

RESULTS: About 18.7% of breast cancers had IHC (ER, PR and HER2) done on them and were all females. The mean age of all subjects was 49.5 years (standard deviation, 13.2; range, 29-78 years). Most (95.8%) of the breast cancers were of invasive ductal carcinoma type, with 77.4% of them been >5 cm. IHC pattern was as follows: ER/PR+, HER2-=19 (39.6%), ER/PR-, HER2- (triple negative [TN])=14 (29.2%), ER/PR+, HER2+=9 (18.8%), ER/PR-, HER2+=6 (12.5%), corresponding to Lumina A, TN/basal-like, Lumina B and HER2 over expressed respectively.

CONCLUSION: Triple negative breast cancers are common in our environment and affect young females most and could be contributory to the poorer prognosis of breast cancer in our environment.}, } @article {pmid25963383, year = {2015}, author = {Siadat, F and Sykes, J and Zlotta, AR and Aldaoud, N and Egawa, S and Pushkar, D and Kuk, C and Bristow, RG and Montironi, R and van der Kwast, T}, title = {Not all gleason pattern 4 prostate cancers are created equal: A study of latent prostatic carcinomas in a cystoprostatectomy and autopsy series.}, journal = {The Prostate}, volume = {75}, number = {12}, pages = {1277-1284}, doi = {10.1002/pros.23009}, pmid = {25963383}, issn = {1097-0045}, mesh = {Adenocarcinoma/*pathology ; Aged ; Autopsy ; Carcinoma, Ductal/*pathology ; Cystectomy/*methods ; Humans ; Japan ; Male ; Neoplasm Grading ; Prognosis ; Prospective Studies ; Prostate/*pathology ; Prostatectomy/*methods ; Prostatic Neoplasms/*pathology ; Russia ; }, abstract = {BACKGROUND: The Gleason grading system represents the cornerstone of the management of prostate cancer. Gleason grade 4 (G4) is a heterogeneous set of architectural patterns, each of which may reflect a distinct prognostic value.

METHODS: We determined the prevalence of the various G4 architectural patterns and intraductal carcinoma (IDC) in latent prostate cancer in contemporary Russian (n = 220) and Japanese (n = 100) autopsy prostates and in cystoprostatectomy (CP) specimens (n = 248) collected in Italy. We studied the association of each G4 pattern with extraprostatic extension (EPE) and tumor volume to gain insight into their natural history. Presence of IDC and nine architectural features of Gleason grade 4 and 5 cancer were recorded.

RESULTS: The prevalence of Gleason score ≥ 7 PC was higher in the autopsy series (11%) compared to the CP series (6.5%, P = 0.04). The prevalence of IDC and carcinoma with a cribriform architecture was 2.2% and 3.4% in the autopsy series and 0.8% and 3.6% in the cystoprostatectomy series, respectively. In multivariable analysis, cribriform architecture was significantly associated with increased tumor volume (P < 0.001) and EPE (OR:11.48, 95%CI:2.30-57.16, P = 0.003). IDC was also significantly associated with EPE (OR:10.08, 95%CI:1.58-64.28, P = 0.014). Small fused glands had a strong negative association with EPE in the autopsy series (OR:0.06, 95%CI:0.01-0.58, P = 0.015).

DISCUSSION: Our study revealed that in latent prostate cancer both cribriform architecture and IDC are uniquely associated with poor pathological outcome features. In contrast, Gleason score 7 (3 + 4) cancers with small-fused gland pattern might possibly include some prostate cancers with a more indolent biology.}, } @article {pmid25961594, year = {2015}, author = {Fisher, JN and Terao, M and Fratelli, M and Kurosaki, M and Paroni, G and Zanetti, A and Gianni, M and Bolis, M and Lupi, M and Tsykin, A and Goodall, GJ and Garattini, E}, title = {MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the growth, survival and motility of breast cancer cells.}, journal = {Oncotarget}, volume = {6}, number = {15}, pages = {13176-13200}, pmid = {25961594}, issn = {1949-2553}, mesh = {Antineoplastic Agents/*pharmacology ; Blotting, Western ; Breast Neoplasms/*pathology ; Carrier Proteins/metabolism ; Cell Growth Processes/*drug effects ; Cell Line, Tumor ; Cell Movement/*drug effects ; Female ; Humans ; Lapatinib ; MicroRNAs/*drug effects/metabolism ; Phosphoinositide Phospholipase C/metabolism ; Polymerase Chain Reaction ; Protein Serine-Threonine Kinases/metabolism ; Quinazolines/*pharmacology ; Receptor, ErbB-2/drug effects ; Receptors, Retinoic Acid/drug effects ; Retinoic Acid Receptor alpha ; Tretinoin/*pharmacology ; }, abstract = {SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and Lapatinib. In this model, the two agents alone or in combination modulate the expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts are organized in four interconnected modules (Module-1 to -4). Module-1 and Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic miRs, while Module-2 contains ATRA/Lapatinib down-regulated and potentially pro-oncogenic miRs. Consistent with this, the expression levels of Module-1/-3 and Module-2 miRs are higher and lower, respectively, in normal mammary tissues relative to ductal-carcinoma-in-situ, invasive-ductal-carcinoma and metastases. This indicates associations between tumor-progression and the expression profiles of Module-1 to -3 miRs. Similar associations are observed with tumor proliferation-scores, staging, size and overall-survival using TCGA (The Cancer Genome Atlas) data. Forced expression of Module-1 miRs, (miR-29a-3p; miR-874-3p) inhibit SKBR3-cell growth and Module-3 miRs (miR-575; miR-1225-5p) reduce growth and motility. Module-2 miRs (miR-125a; miR-193; miR-210) increase SKBR3 cell growth, survival and motility. Some of these effects are of general significance, being replicated in other breast cancer cell lines representing the heterogeneity of this disease. Finally, our study demonstrates that HIPK2-kinase and the PLCXD1-phospholipase-C are novel targets of miR-193a-5p/miR-210-3p and miR-575/miR-1225-5p, respectively.}, } @article {pmid25955408, year = {2015}, author = {Morikawa, A and Takeuchi, T and Kito, Y and Saigo, C and Sakuratani, T and Futamura, M and Yoshida, K}, title = {Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0125762}, pmid = {25955408}, issn = {1932-6203}, mesh = {Apoptosis Regulatory Proteins/antagonists & inhibitors/genetics/*metabolism ; Beclin-1 ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cells, Cultured ; Coculture Techniques ; Cytokines/metabolism ; Discoidin Domain Receptors ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Interleukin-10 Receptor beta Subunit/metabolism ; Interleukin-1beta/genetics/metabolism ; Lymphatic Metastasis ; MCF-7 Cells ; Membrane Proteins/antagonists & inhibitors/genetics/*metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA Interference ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Receptors, Cytokine/metabolism ; Receptors, Mitogen/genetics/metabolism ; Tumor Microenvironment ; }, abstract = {We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2). Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.}, } @article {pmid25955205, year = {2015}, author = {Gutierrez, DA and Muralidhar, S and Feyerabend, TB and Herzig, S and Rodewald, HR}, title = {Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.}, journal = {Cell metabolism}, volume = {21}, number = {5}, pages = {678-691}, doi = {10.1016/j.cmet.2015.04.013}, pmid = {25955205}, issn = {1932-7420}, mesh = {Animals ; Gene Deletion ; Hematopoiesis ; *Insulin Resistance ; Male ; Mast Cells/immunology/metabolism/*pathology ; Metabolic Syndrome/genetics ; Mice ; Mice, Inbred C57BL ; Obesity/*genetics/immunology/pathology ; Stem Cell Factor/*genetics/immunology ; Transcriptome ; }, abstract = {Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome.}, } @article {pmid25953261, year = {2015}, author = {Jiang, G and Zhang, X and Zhang, Y and Wang, L and Fan, C and Xu, H and Miao, Y and Wang, E}, title = {A novel biomarker C6orf106 promotes the malignant progression of breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {10}, pages = {7881-7889}, pmid = {25953261}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Movement ; *Cell Proliferation ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Triple Negative Breast Neoplasms/genetics/metabolism/*pathology ; Tumor Cells, Cultured ; }, abstract = {C6orf106 (chromosome 6 open reading frame 106) is a recently discovered protein encoded by the 6th chromosome. Though many proteins encoded by chromosome 6 are reportedly related to cancer, schizophrenia, autoimmunity and many other diseases, the function of C6orf106 was not well demonstrated so far. As measured by immunohistochemical staining, C6orf106 was positive in normal breast duct myoepithelial cells (92.31 %, 72/78), but negative in normal breast duct glandular epithelial cells (3.85 %, 3/78). In breast ductal carcinoma in situ, C6orf106 showed weakly or moderately positive (77.97 %, 46/59), but it was significantly strongly positive in invasive ductal carcinoma (79.57 %, 148/186). The expression intensity of C6orf106 seemed increased significantly along with the malignancy of breast cancer (p < 0.001). Additionally, C6orf106 expression was significantly correlated with TNM stage (p = 0.001 and p = 0.004) and lymph node metastasis (p = 0.018 and p = 0.025) of the overall and the triple-negative breast cancer, respectively. Consistently, we found that the interference of C6orf106 was able to inhibit cell proliferation and invasion of two triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, accompanied by the decrease of cyclin A2, cyclin B1, c-myc, and N-cadherin and the increase of E-cadherin. Collectively, these results indicate that C6orf106 may promote tumor progression in the invasive breast cancer, particularly in triple-negative breast cancer, and C6orf106 might serve as a novel therapeutic target of breast cancer, especially for triple-negative breast cancer.}, } @article {pmid25950745, year = {2015}, author = {Xiang, S and Liu, YM and Chen, X and Wang, YW and Ma, RR and Wu, XJ and Gao, P}, title = {ZEB1 expression is correlated with tumor metastasis and reduced prognosis of breast carcinoma in Asian patients.}, journal = {Cancer investigation}, volume = {33}, number = {6}, pages = {225-231}, doi = {10.3109/07357907.2015.1022258}, pmid = {25950745}, issn = {1532-4192}, mesh = {Adult ; Aged ; Asian People ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Homeodomain Proteins/*biosynthesis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis/pathology ; Prognosis ; Transcription Factors/*biosynthesis ; Zinc Finger E-box-Binding Homeobox 1 ; }, abstract = {Tumor metastasis is one of the key events leading to tumor relapse and poor prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated in human carcinogenesis. However, involvement of ZEB1 deregulation in tumorigenesis in Asian patients with breast carcinoma remains elusive. The present study included 102 Asian patients with breast carcinoma treated by surgery from January of 2005 to December of 2006, and the expression of ZEB1 was evaluated by immunohistochemistry. To further assess the prognostic value of ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of ZEB1 expression was found in carcinomas with higher aggressive potential. We also correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in invasive ductal carcinoma. Furthermore, our data suggested an elevated level of Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced overall survival and disease-free survival were observed in cases with positive ZEB1 expression than that in negative cases. Our results correlated ZEB1 with aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as a prognostic marker in breast carcinoma.}, } @article {pmid25948818, year = {2015}, author = {Alissafi, T and Hatzioannou, A and Ioannou, M and Sparwasser, T and Grün, JR and Grützkau, A and Verginis, P}, title = {De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {194}, number = {12}, pages = {5812-5824}, doi = {10.4049/jimmunol.1500111}, pmid = {25948818}, issn = {1550-6606}, mesh = {Animals ; Autoantigens/*immunology ; Autoimmunity ; Chemotaxis/immunology ; Cluster Analysis ; Dendritic Cells/*immunology ; Disease Models, Animal ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/genetics/immunology/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Gene Expression Profiling ; Immune Tolerance ; Inflammation/genetics/*immunology/metabolism ; Interleukin-10/metabolism ; Lymph Nodes/*immunology ; Lymphocyte Depletion ; Mice ; Mice, Knockout ; Myelin-Oligodendrocyte Glycoprotein/administration & dosage/immunology ; Peptide Fragments/administration & dosage/immunology ; Receptors, CCR7/genetics/metabolism ; Signal Transduction ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {Foxp3(+) regulatory T cell (Treg)-based immunotherapy holds promise for autoimmune diseases. However, this effort has been hampered by major caveats, including the low frequency of autoantigen-specific Foxp3(+) Tregs and lack of understanding of their molecular and cellular targets, in an unmanipulated wild-type (WT) immune repertoire. In this study, we demonstrate that infusion of myelin in WT mice results in the de novo induction of myelin-specific Foxp3(+) Tregs in WT mice and amelioration of experimental autoimmune encephalomyelitis. Myelin-specific Foxp3(+) Tregs exerted their effect both by diminishing Ag-bearing inflammatory dendritic cell (iDC) recruitment to lymph nodes and by impairing their function. Transcriptome analysis of ex vivo-isolated Treg-exposed iDCs showed significant enrichment of transcripts involved in functional properties of iDCs, including chemotaxis-related genes. To this end, CCR7 expression by iDCs was significantly downregulated in tolerant mice and this was tightly regulated by the presence of IL-10. Collectively, our data demonstrate a novel model for deciphering the Ag-specific Foxp3(+) Treg-mediated mechanisms of tolerance and delineate iDCs as a Foxp3(+) Treg cellular target in unmanipulated mice.}, } @article {pmid25947632, year = {2015}, author = {Maramba, ID and Davey, A and Elliott, MN and Roberts, M and Roland, M and Brown, F and Burt, J and Boiko, O and Campbell, J}, title = {Web-based textual analysis of free-text patient experience comments from a survey in primary care.}, journal = {JMIR medical informatics}, volume = {3}, number = {2}, pages = {e20}, pmid = {25947632}, issn = {2291-9694}, support = {RP-PG-0608-10050/DH_/Department of Health/United Kingdom ; }, abstract = {BACKGROUND: Open-ended questions eliciting free-text comments have been widely adopted in surveys of patient experience. Analysis of free text comments can provide deeper or new insight, identify areas for action, and initiate further investigation. Also, they may be a promising way to progress from documentation of patient experience to achieving quality improvement. The usual methods of analyzing free-text comments are known to be time and resource intensive. To efficiently deal with a large amount of free-text, new methods of rapidly summarizing and characterizing the text are being explored.

OBJECTIVE: The aim of this study was to investigate the feasibility of using freely available Web-based text processing tools (text clouds, distinctive word extraction, key words in context) for extracting useful information from large amounts of free-text commentary about patient experience, as an alternative to more resource intensive analytic methods.

METHODS: We collected free-text responses to a broad, open-ended question on patients' experience of primary care in a cross-sectional postal survey of patients recently consulting doctors in 25 English general practices. We encoded the responses to text files which were then uploaded to three Web-based textual processing tools. The tools we used were two text cloud creators: TagCrowd for unigrams, and Many Eyes for bigrams; and Voyant Tools, a Web-based reading tool that can extract distinctive words and perform Keyword in Context (KWIC) analysis. The association of patients' experience scores with the occurrence of certain words was tested with logistic regression analysis. KWIC analysis was also performed to gain insight into the use of a significant word.

RESULTS: In total, 3426 free-text responses were received from 7721 patients (comment rate: 44.4%). The five most frequent words in the patients' comments were "doctor", "appointment", "surgery", "practice", and "time". The three most frequent two-word combinations were "reception staff", "excellent service", and "two weeks". The regression analysis showed that the occurrence of the word "excellent" in the comments was significantly associated with a better patient experience (OR=1.96, 95%CI=1.63-2.34), while "rude" was significantly associated with a worse experience (OR=0.53, 95%CI=0.46-0.60). The KWIC results revealed that 49 of the 78 (63%) occurrences of the word "rude" in the comments were related to receptionists and 17(22%) were related to doctors.

CONCLUSIONS: Web-based text processing tools can extract useful information from free-text comments and the output may serve as a springboard for further investigation. Text clouds, distinctive words extraction and KWIC analysis show promise in quick evaluation of unstructured patient feedback. The results are easily understandable, but may require further probing such as KWIC analysis to establish the context. Future research should explore whether more sophisticated methods of textual analysis (eg, sentiment analysis, natural language processing) could add additional levels of understanding.}, } @article {pmid25941593, year = {2014}, author = {Bloy, N and Pol, J and Aranda, F and Eggermont, A and Cremer, I and Fridman, WH and Fučíková, J and Galon, J and Tartour, E and Spisek, R and Dhodapkar, MV and Zitvogel, L and Kroemer, G and Galluzzi, L}, title = {Trial watch: Dendritic cell-based anticancer therapy.}, journal = {Oncoimmunology}, volume = {3}, number = {11}, pages = {e963424}, pmid = {25941593}, issn = {2162-4011}, abstract = {The use of patient-derived dendritic cells (DCs) as a means to elicit therapeutically relevant immune responses in cancer patients has been extensively investigated throughout the past decade. In this context, DCs are generally expanded, exposed to autologous tumor cell lysates or loaded with specific tumor-associated antigens (TAAs), and then reintroduced into patients, often in combination with one or more immunostimulatory agents. As an alternative, TAAs are targeted to DCs in vivo by means of monoclonal antibodies, carbohydrate moieties or viral vectors specific for DC receptors. All these approaches have been shown to (re)activate tumor-specific immune responses in mice, often mediating robust therapeutic effects. In 2010, the first DC-based preparation (sipuleucel-T, also known as Provenge®) has been approved by the US Food and Drug Administration (FDA) for use in humans. Reflecting the central position occupied by DCs in the regulation of immunological tolerance and adaptive immunity, the interest in harnessing them for the development of novel immunotherapeutic anticancer regimens remains high. Here, we summarize recent advances in the preclinical and clinical development of DC-based anticancer therapeutics.}, } @article {pmid25940209, year = {2015}, author = {Di Bonito, M and Cantile, M and Cerrone, M and Liguori, G and Botti, G}, title = {Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct Breasts.}, journal = {The breast journal}, volume = {21}, number = {4}, pages = {428-430}, doi = {10.1111/tbj.12426}, pmid = {25940209}, issn = {1524-4741}, mesh = {Adenoma, Pleomorphic/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasms, Multiple Primary/*pathology ; Parotid Neoplasms/*pathology ; }, } @article {pmid25939640, year = {2015}, author = {Yoon, HJ and Kim, Y and Chang, KT and Kim, BS}, title = {Prognostic value of semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.}, journal = {Annals of nuclear medicine}, volume = {29}, number = {7}, pages = {553-560}, doi = {10.1007/s12149-015-0977-3}, pmid = {25939640}, issn = {1864-6433}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biological Transport ; Breast/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Organ Specificity ; Prognosis ; Radionuclide Imaging ; Recurrence ; Technetium Tc 99m Sestamibi/*metabolism ; }, abstract = {OBJECTIVES: This study investigated the prognostic value of preoperative breast-specific gamma imaging (BSGI) uptake measured by a semi-quantitative method in invasive ductal carcinoma (IDC).

METHODS: One hundred and sixty-two women with IDC who underwent preoperative BSGI were retrospectively enrolled. The tumor-to-normal tissue ratio (TNR) was measured on BSGI and correlated with histologic prognostic factors. The prognostic impact of TNR was tested with regard to progression-free survival (PFS) and compared with established prognostic factors.

RESULTS: High TNR was significantly correlated with tumor size >2 cm (p < 0.001), high nuclear grade (p = 0.04), high histologic grade (p = 0.01), axillary node positivity (p = 0.04), ER negativity (p = 0.03), HER2 positivity (p = 0.01), and high MIB-1 index (p = 0.001). Among 162 patients, 14 experienced recurrence during mean follow-up time of 34.7 ± 14.9 months. In Kaplan-Meier survival analyses, high TNR (p < 0.001), high nuclear grade (p = 0.02), high histologic grade (p = 0.007), ER/PR negativity (p = 0.003 and p < 0.001, respectively), HER2 positivity (p = 0.01), triple negativity (p = 0.02), and high MIB-1 index (p = 0.02) showed a significant relationship with poor prognosis. Among them, high TNR was an independent poor prognostic factor in a multivariate regression analysis (p = 0.01).

CONCLUSIONS: High BSGI uptake measured by a semi-quantitative method was correlated with diverse poor histologic prognostic factors and was an independent poor prognostic factor in invasive ductal cancer.}, } @article {pmid25936264, year = {2015}, author = {De Lucia, N and Trojano, L and Vitale, C and Grossi, D and Barone, P and Santangelo, G}, title = {The closing-in phenomenon in Parkinson's disease.}, journal = {Parkinsonism & related disorders}, volume = {21}, number = {7}, pages = {793-796}, doi = {10.1016/j.parkreldis.2015.04.013}, pmid = {25936264}, issn = {1873-5126}, mesh = {Aged ; Apraxias/*diagnosis/*psychology ; *Executive Function ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*diagnosis/*psychology ; Psychomotor Performance ; Retrospective Studies ; }, abstract = {INTRODUCTION: Closing-in (CI) is a peculiar phenomenon consisting in the tendency to copy drawings close to or superimposed on a model. Recent findings showed that CI can be associated with frontal/executive dysfunctions, likely determining a failure in high-level monitoring of attention-action circuits. CI has been often observed in demented patients, but scarce data are available about CI in patients with Parkinson's disease (PD). In the present study, we detected occurrence of CI and investigated the cognitive processes associated to this phenomenon in a large sample of non-demented PD patients.

METHODS: We retrospectively analysed graphic reproductions in a copying task of 100 non-demented PD patients who had also completed cognitive, behavioural, and motor screening assessment.

RESULTS: CI phenomenon occurred in 50/100 non-demented PD patients (50%; 118/700 drawings). Among these patients, 46/50 patients copied drawings close to the model (near-CI), 2/50 patients superimposed their copy directly on the model (adherent-CI), whereas 2/50 patients showed both near-and adherent-CI. MANOVA showed that non-demented PD patients with CI showed more severe impairment on frontal/executive functions and visuo-constructional abilities than non-demented PD patients without CI. However, the logistic regression model revealed that occurrence of CI was significantly associated to lower scores on frontal/executive tasks only.

CONCLUSION: CI can be found in a large proportion of non-demented PD patients, and it is related to frontal monitoring defects that could hamper inhibition of action and attention toward a model.}, } @article {pmid25932376, year = {2015}, author = {Kappikeri, VK and Kriplani, AM}, title = {Bilateral synchronous carcinoma breast- a rare case presentation.}, journal = {SpringerPlus}, volume = {4}, number = {}, pages = {193}, pmid = {25932376}, issn = {2193-1801}, abstract = {INTRODUCTION: Bilateral Breast Carcinoma (BBC) is a rare entity with incidence of synchronous carcinoma being 2-5% of all breast malignancies, which is much less than metachronous carcinoma. Synchronicity/ metachronicity are usually associated with local and lymphatic spread and with blood-borne spread to lungs, bones and liver. Moreover BBC are mostly lobular carcinomas but we report a rare case of Infiltrating Ductal Carcinoma (IDC) as the primary carcinoma and Lobular Carcinoma as the secondary.

CASE DESCRIPTION: 56 year old female who presented with a Stage IIIB fungating growth around 10x8cm in the lower inner, lower outer and upper outer quadrant of right breast since 6 months and a StageIIA 4x4cm tumour felt in the left breast in the upper inner and lower outer quadrant. Wedge biopsy of the right breast fungating mass showed Ductal Carcinoma and FNAC of the left breast lump suggested Lobular carcinoma which was confirmed on Histopathology after surgery. Patient was subjected to Hormonal therapy (Tab Tamoxifen), chemotherapy (Cyclophosphamide, 5 FU, and Doxorubicin) followed by Radiotherapy. Patient recovered well and shows no recurrence or signs of metastasis in the 8 months of follow up.

DISCUSSION AND EVALUATION: Different histological subtypes with different grades of tumour in both breasts suggested two different synchronous primary tumours. Early detection of the contralateral tumour is of utmost importance emphasising the significance of breast self-examination. Screening tools like MRI have a greater sensitivity compared to Mammography. There are no clear treatment guidelines for bilateral breast cancer. Patients are often treated with bilateral mastectomy, with breast conservative surgery having unclear importance.

CONCLUSION: Meticulous diagnosis and appropriate management help to improve the longitivity with an improved quality of life.}, } @article {pmid25931942, year = {2015}, author = {Ünsal, MG and Dural, AC and Çelik, MF and Akarsu, C and Başoğlu, İ and Dilege, ME and Kapan, S and Alış, H}, title = {The adaptation process of a teaching and research hospital to changing trends in modern breast surgery.}, journal = {Ulusal cerrahi dergisi}, volume = {31}, number = {1}, pages = {34-38}, pmid = {25931942}, issn = {1300-0705}, abstract = {OBJECTIVE: Minimally invasive surgery is increasingly gaining importance in breast surgery parallel to other surgical branches. Sentinel lymph node biopsy (SLNB) is a method that has radically changed the approach to breast surgery in the last decade of the 20(th) century. In this study, we aimed to evaluate the adaptation process to these alterations in breast surgery at our clinic.

MATERIAL AND METHODS: Patients who underwent surgery with a diagnosis of breast cancer in our clinic between April 2010 and November 2013 were retrospectively evaluated in terms of demographic characteristics, the number of operations and type of surgical methods applied according to years, SLNB performance rate, and results of frozen section and histopathological analysis. The first year of SLNB practice was accepted as part of the learning curve, and 24 patients who were operated during that period underwent routine axillary dissection.

RESULTS: The median age of 198 patients who were included in the study was 55 years (25-89). It was detected that the number of cases who underwent surgery for breast cancer increased in years, that the SLNB application rate increased from 37% to 66% between 2010 and 2013 (p=0.01), and SLNB staining rates increased from 70% to 94% (p=0.03). When only results from the last four years were evaluated, the mean staining rate in patients with SLNB (n=105) was 88% (n=92), with positive histopathology in 32% of these cases (n=30). Despite a decreasing trend over the years, a metastatic axillary lymph node was detected in paraffin block evaluation in spite of negative frozen section examination of SLNB in five cases, and 5 patients (5%) out of 97 patients who underwent breast conserving surgery required re-excision. The histopathological diagnosis was invasive ductal carcinoma in 84% (n=167) of patients.

CONCLUSION: It was observed that during the four-year period of adaptation, the application rate of breast conserving surgery and SLNB reached accepted standards, and that both the technical problems encountered in SLNB and the requirement for re-excision after breast conserving surgery significantly decreased with increasing case volume and experience.}, } @article {pmid25931358, year = {2015}, author = {Dopheide, JF and Zeller, GC and Kuhlmann, M and Girndt, M and Sester, M and Sester, U}, title = {Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {24}, number = {2}, pages = {257-266}, doi = {10.17219/acem/40463}, pmid = {25931358}, issn = {1899-5276}, mesh = {Age Factors ; Aged ; Biomarkers/metabolism ; Case-Control Studies ; *Cell Differentiation/drug effects ; Cells, Cultured ; Dendritic Cells/drug effects/*immunology/metabolism ; Female ; GPI-Linked Proteins/immunology/metabolism ; Humans ; Kidney Failure, Chronic/*immunology/therapy ; Lipopolysaccharide Receptors/immunology/metabolism ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Monocytes/drug effects/*immunology/metabolism ; Phenotype ; Receptors, IgG/immunology/metabolism ; Renal Dialysis ; Time Factors ; }, abstract = {BACKGROUND: Dendritic cells (DC) play an important role in the induction of immune responses. Patients with end stage renal disease (ESRD) suffer from chronic inflammation, leading to a secondary, uremic immunodeficiency associated with alterations in monocyte subpopulations with increased proinflammatory capacities.

OBJECTIVES: The aim of this study was to examine, under isolated conditions, whether alterations in monocyte subpopulations may affect in vitro maturation of dendritic cells (DC) in patients with ESRD, thus allowing us to draw conclusions for the situation in vivo.

MATERIAL AND METHODS: Monocytes from 30 patients undergoing hemodialysis (HD) and 15 healthy volunteers were enriched from peripheral blood leukocytes, differentiated into immature DC (iDC) in medium containing IL-4 and GM-CSF, and were induced with LPS to differentiate into mature DC (mDC). Monocyte subpopulations and DC maturation stages were phenotypically characterized using flow-cytometry.

RESULTS: Although phenotypically indistinguishable, the number of both iDC and mDC that were generated from uremic monocytes was significantly higher compared to those from healthy controls (p=0.02 and p=0.03, respectively). This was associated with an increased number of CD14+ CD16+ monocytes (p=0.02) and by a higher maturation efficiency of mDC in patients (p=0.04).

CONCLUSIONS: A high percentage of CD14+ CD16+ monocytes in patients with ESRD is associated with an increased propensity to differentiate into DC. This indicates that chronic inflammation may substantiate the biased consistence of monocyte subpopulations leading to profound alteration in DC generation and maturation in ESRD.}, } @article {pmid25928089, year = {2015}, author = {Katanov, C and Lerrer, S and Liubomirski, Y and Leider-Trejo, L and Meshel, T and Bar, J and Feniger-Barish, R and Kamer, I and Soria-Artzi, G and Kahani, H and Banerjee, D and Ben-Baruch, A}, title = {Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway.}, journal = {Stem cell research & therapy}, volume = {6}, number = {1}, pages = {87}, pmid = {25928089}, issn = {1757-6512}, mesh = {Blotting, Western ; Bone Marrow Cells/cytology ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Chemokine CCL2/analysis ; Chemokine CCL5/analysis ; Culture Media, Conditioned/pharmacology ; Female ; Fibroblasts/cytology/*metabolism ; Humans ; Interleukin-1beta/pharmacology ; Interleukin-8/analysis ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism ; MCF-7 Cells ; Mesenchymal Stem Cells/cytology/*drug effects/metabolism ; NF-kappa B/*metabolism ; RNA Interference ; Signal Transduction ; Transcription Factor RelA/antagonists & inhibitors/genetics/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism/*pharmacology ; Up-Regulation/drug effects ; }, abstract = {INTRODUCTION: Breast cancer progression is promoted by stromal cells that populate the tumors, including cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs). The activities of CAFs and MSCs in breast cancer are integrated within an intimate inflammatory tumor microenvironment (TME) that includes high levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Here, we identified the impact of TNF-α and IL-1β on the inflammatory phenotype of CAFs and MSCs by determining the expression of inflammatory chemokines that are well-characterized as pro-tumorigenic in breast cancer: CCL2 (MCP-1), CXCL8 (IL-8) and CCL5 (RANTES).

METHODS: Chemokine expression was determined in breast cancer patient-derived CAFs by ELISA and in patient biopsies by immunohistochemistry. Chemokine levels were determined by ELISA in (1) human bone marrow-derived MSCs stimulated by tumor conditioned media (Tumor CM) of breast tumor cells (MDA-MB-231 and MCF-7) at the end of MSC-to-CAF-conversion process; (2) Tumor CM-derived CAFs, patient CAFs and MSCs stimulated by TNF-α (and IL-1β). The roles of AP-1 and NF-κB in chemokine secretion were analyzed by Western blotting and by siRNAs to c-Jun and p65, respectively. Migration of monocytic cells was determined in modified Boyden chambers.

RESULTS: TNF-α (and IL-1β) induced the release of CCL2, CXCL8 and CCL5 by MSCs and CAFs generated by prolonged stimulation of MSCs with Tumor CM of MDA-MB-231 and MCF-7 cells. Patient-derived CAFs expressed CCL2 and CXCL8, and secreted CCL5 following TNF-α (and IL-1β) stimulation. CCL2 was expressed in CAFs residing in proximity to breast tumor cells in biopsies of patients diagnosed with invasive ductal carcinoma. CCL2 release by TNF-α-stimulated MSCs was mediated by TNF-RI and TNF-RII, through the NF-κB but not via the AP-1 pathway. Exposure of MSCs to TNF-α led to potent CCL2-induced migration of monocytic cells, a process that may yield pro-cancerous myeloid infiltrates in breast tumors.

CONCLUSIONS: Our novel results emphasize the important roles of inflammation-stroma interactions in breast cancer, and suggest that NF-κB may be a potential target for inhibition in tumor-adjacent stromal cells, enabling improved tumor control in inflammation-driven malignancies.}, } @article {pmid25927974, year = {2015}, author = {Shenker, NS and Flower, KJ and Wilhelm-Benartzi, CS and Dai, W and Bell, E and Gore, E and El Bahrawy, M and Weaver, G and Brown, R and Flanagan, JM}, title = {Transcriptional implications of intragenic DNA methylation in the oestrogen receptor alpha gene in breast cancer cells and tissues.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {337}, pmid = {25927974}, issn = {1471-2407}, support = {13086/CRUK_/Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; A13086//Cancer Research UK/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cell Line, Tumor ; DNA Methylation ; Epigenesis, Genetic ; Estrogen Receptor alpha/*genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Glands, Human/metabolism ; Milk, Human/cytology ; *Promoter Regions, Genetic ; Sequence Analysis, DNA ; Transcription, Genetic ; }, abstract = {BACKGROUND: DNA methylation variability regions (MVRs) across the oestrogen receptor alpha (ESR1) gene have been identified in peripheral blood cells from breast cancer patients and healthy individuals. In contrast to promoter methylation, gene body methylation may be important in maintaining active transcription. This study aimed to assess MVRs in ESR1 in breast cancer cell lines, tumour biopsies and exfoliated epithelial cells from expressed breast milk (EBM), to determine their significance for ESR1 transcription.

METHODS: DNA methylation levels in eight MVRs across ESR1 were assessed by pyrosequencing bisulphite-converted DNA from three oestrogen receptor (ER)-positive and three ER-negative breast cancer cell lines. DNA methylation and expression were assessed following treatment with DAC (1 μM), or DMSO (controls). ESR1 methylation levels were also assayed in DNA from 155 invasive ductal carcinoma biopsies provided by the Breast Cancer Campaign Tissue Bank, and validated with DNA methylation profiles from the TCGA breast tumours (n = 356 ER-pos, n = 109 ER-neg). DNA methylation was profiled in exfoliated breast epithelial cells from EBM using the Illumina 450 K (n = 36) and pyrosequencing in a further 53 donor samples. ESR1 mRNA levels were measured by qRT-PCR.

RESULTS: We show that ER-positive cell lines had unmethylated ESR1 promoter regions and highly methylated intragenic regions (median, 80.45%) while ER-negative cells had methylated promoters and lower intragenic methylation levels (median, 38.62%). DAC treatment increased ESR1 expression in ER-negative cells, but significantly reduced methylation and expression of ESR1 in ER-positive cells. The ESR1 promoter was unmethylated in breast tumour biopsies with high levels of intragenic methylation, independent of ER status. However, ESR1 methylation in the strongly ER-positive EBM DNA samples were very similar to ER-positive tumour cell lines.

CONCLUSION: DAC treatment inhibited ESR1 transcription in cells with an unmethylated ESR1 promoter and reduced intragenic DNA methylation. Intragenic methylation levels correlated with ESR1 expression in homogenous cell populations (cell lines and exfoliated primary breast epithelial cells), but not in heterogeneous tumour biopsies, highlighting the significant differences between the in vivo tumour microenvironment and individual homogenous cell types. These findings emphasise the need for care when choosing material for epigenetic research and highlights the presence of aberrant intragenic methylation levels in tumour tissue.}, } @article {pmid25924435, year = {2015}, author = {Zhou, L and Zhao, YH and Wang, XD and Jiang, SF and Li, H}, title = {[Expression of fatty acid synthase and adipocyte fatty acid-binding protein and the relationship with the clinicopathological characteristics in human infiltrating ductal breast cancer].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {46}, number = {2}, pages = {228-233}, pmid = {25924435}, issn = {1672-173X}, mesh = {Adipocytes ; Blotting, Western ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cell Line, Tumor ; Fatty Acid Synthase, Type I/*metabolism ; Fatty Acid-Binding Proteins/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; }, abstract = {OBJECTIVE: To study the expression of fatty acid synthase (FASN) and adipocyte fatty acid-binding protein (A-FABP) in human infiltrating ductal breast cancer (IDC) tissues and hunman breast cancer cells and the relationship with the clinicopathogical characteristics. To further explore the relationship between FASN and A-FABP, and the relevance of the invasion in cancer cell.

METHODS: The expression of FASN and A-FABP was detected in 58 cases of human infiltrating ductal breast cancer and 12 cases of human normal breast tissues by immunohistochemistry technique, calculated positive expression percentage according to the number of positive cells percentage and the staining degree of positive sediment. The cell wound-healing assay was applied to detect the invasion of SKBR3 and MCF-7 cells. Western blot was used to detect the expression of FASN and A-FABP in MCF-7 and SKBR3 cells.

RESULTS: The positive rates of FASN and A-FABP were 8.3% (1/12) and 16.7% (1/6) respectively in 12 cases of normal breast tissues by immunohistochemistry. In 58 cases of IDC tissues, the positive rates of FASN and A-FABP were 72.4% (42/58) and 79.3% (46/58) respectively. The differences of the positive rates of FASN and A-FABP in normal breast and IDC tissues were statistically significant (P<0.01, P2 cm) when compared with lymph node metastasis negative group or the diameter < or =2 cm group, the differences were statistically significant (P<0.01). In IDC group, the expression of FASN correlated with A-FABP (r=0.797, P<0.001), The migration rate of SKBR3 was significantly higher than MCF-7 cell at 12, 24 h (P<0.05), FASN expression in SKBR3 was higher than that in MCF-7.

CONCLUSION: FASN and A-FABP might associated with the lymph node metastasis and tumor size, and there was correlation between FASN and A-FABP in human IDC tissues. FASN may associated with the invasion and metastasis in breast cancer cells.}, } @article {pmid25921169, year = {2015}, author = {Sushma, C and Prasad, S and Devi, R and Murthy, S and Rao, Ts and Naidu, C}, title = {High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {8}, pages = {3505-3508}, doi = {10.7314/apjcp.2015.16.8.3505}, pmid = {25921169}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Codon ; Female ; Genetic Predisposition to Disease ; Humans ; India ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; White People/*genetics ; ras Proteins/*genetics ; }, abstract = {BACKGROUND: Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population.

MATERIALS AND METHODS: A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method.

RESULTS: We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study.

CONCLUSIONS: Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.}, } @article {pmid25919239, year = {2015}, author = {Kim, EJ and Kim, SH and Park, GE and Kang, BJ and Song, BJ and Kim, YJ and Lee, D and Ahn, H and Kim, I and Son, YH and Grimm, R}, title = {Histogram analysis of apparent diffusion coefficient at 3.0t: Correlation with prognostic factors and subtypes of invasive ductal carcinoma.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {42}, number = {6}, pages = {1666-1678}, doi = {10.1002/jmri.24934}, pmid = {25919239}, issn = {1522-2586}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/classification/metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/metabolism/*pathology ; *Data Interpretation, Statistical ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Ki-67 Antigen/classification/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Observer Variation ; Prognosis ; Receptor, ErbB-2/metabolism ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {PURPOSE: To evaluate apparent diffusion coefficient (ADC) histogram parameters that show correlations with prognostic factors and subtypes of breast cancer.

MATERIALS AND METHODS: At 3.0T, various ADC histogram parameters were calculated including the entire tumor volume in 173 invasive ductal carcinomas: the minimum, 10th percentile, mean, median, 90th percentile, and maximum. ADC parameters were correlated with prognostic factors and subtype.

RESULTS: The mean ADCmedian value was significantly higher in the group with lymph node metastasis, HER2 positivity, and a Ki-67 value <14% than in the group with negativity for lymph node metastasis, HER2 negativity, and a Ki-67 value ≥14% (0.907, 0.978, and 0.941 vs. 0.735, 0.778, and 0.761 × 10(-3) mm(2) /s, respectively) (P < 0.01). There was no significant correlation between ADCmedian and tumor size, histologic grade, estrogen receptor expression, and progesterone receptor expression (P = 0.272, 0.113, 0.261, and 0.181, respectively). For most ADC parameters except for ADCmin , the mean of variable ADC parameters of HER2-positive, luminal A, luminal B-HER2(+), triple-negative, and luminal B-HER2(-) diseases were arranged in descending order (1.175, 0.936, 0.863, 0.811, and 0.665 × 10(-3) mm(2) /s in ADCmedian , respectively) with statistical significant difference (P < 0.001). In multivariate analysis, histologic grade, the Ki-67 index, and HER2 expression were statistically significant explanatory prognostic factors for ADCmedian and the Ki-67 index had the most robust effects on ADC parameters (standardized coefficient = -0.317).

CONCLUSION: Various ADC parameters were correlated with prognostic factors and subtype, except for ADCmin . HER2 positivity showed high ADC values and high Ki-67 index revealed low ADC values.}, } @article {pmid25917338, year = {2015}, author = {Chen, Z and Chen, N and Shen, P and Gong, J and Li, X and Zhao, T and Liao, B and Liu, L and Liu, Z and Zhang, X and Liu, J and Peng, Z and Chen, X and Xu, M and Gui, H and Zhang, P and Wei, Q and Zhou, Q and Zeng, H}, title = {The presence and clinical implication of intraductal carcinoma of prostate in metastatic castration resistant prostate cancer.}, journal = {The Prostate}, volume = {75}, number = {12}, pages = {1247-1254}, doi = {10.1002/pros.23005}, pmid = {25917338}, issn = {1097-0045}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Biopsy ; Carcinoma, Ductal/drug therapy/*pathology ; Disease Progression ; Docetaxel ; Humans ; Incidence ; Kallikreins/blood ; Male ; Middle Aged ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/drug therapy/*pathology ; Prostatic Neoplasms, Castration-Resistant/drug therapy/*pathology ; Taxoids/therapeutic use ; }, abstract = {BACKGROUND: Intraductal carcinoma of prostate (IDC-P) is always underestimated pathological pattern in prostate cancer and its role is still unclear in castration resistant prostate cancer (CRPC). This study was conducted to investigate the presence and the roles of IDC-P in patients with metastatic CRPC.

METHODS: 45 patients with initially diagnosed metastatic prostate cancer and then progressed to CRPC, were included. All of them were received twice transperineal biopsies at the time of initial diagnosis and the time of CRPC. All samples were retrieved to detect the presence of IDC-P. PSA doubling time (PSADT) was considered as a parameter presenting the progression of CRPC. The relationships between IDC-P and other clinicopathological variables were analyzed.

RESULTS: IDC-P was found only in 20% (9/45) cases at initial diagnosis, whereas, it increased to 62.5% (28/45) at the time of CRPC (χ(2) = 16.568, P = 0.000). Compared to acinar adenocarcinoma components in tumor tissues, IDC-P components, especially solid subtype, had obviously poor/no response to androgen deprivation therapy (ADT). In addition, among patients treated with docetaxel-based chemotherapy (n = 24), patients with IDC-P also showed more unfavorable response than those without IDC-P (20% vs. 66.7%, P = 0.022). The presence of IDC-P and serum testosterone at the time of CRPC, were significantly associated with rapid disease progression. 13/28 (46.4%) CRPC with IDC-P had PSADT less than 30 days, while, only 1/17 (5.9%) patient without IDC-P had a less than 30 days PSADT (χ(2) = 8.114, P = 0.004). Limitations included the relative short follow-up time and a relative small cohort.

CONCLUSIONS: The presence of IDC-P was significantly associated with rapid progression of CRPC. And its presence could suggest the poor response to initial ADT and sequential docetaxel-based chemotherapy. Detection of IDC-P should be of importance in CRPC, and re-biopsy at the time of CRPC might be one of practical solutions. The mechanism of the ADT and docetaxel resistance to IDC-P needed to be further investigated.}, } @article {pmid25916980, year = {2015}, author = {Kamrava, M and Kuske, RR and Anderson, B and Chen, P and Hayes, J and Quiet, C and Wang, PC and Veruttipong, D and Snyder, M and Jeffrey Demanes, D}, title = {Outcomes of Breast Cancer Patients Treated with Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.}, journal = {Annals of surgical oncology}, volume = {22 Suppl 3}, number = {}, pages = {S404-11}, doi = {10.1245/s10434-015-4563-7}, pmid = {25916980}, issn = {1534-4681}, mesh = {Adult ; *Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Catheterization/*methods ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasm Staging ; Prognosis ; Radiotherapy Dosage ; *Registries ; Retrospective Studies ; Survival Rate ; }, abstract = {PURPOSE: To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation with interstitial multicatheter brachytherapy by a cooperative group of institutions.

METHODS: From 1992 to 2013, a total of 1356 patients were treated with breast-conserving surgery and adjuvant accelerated partial breast irradiation using interstitial multicatheter brachytherapy. A total of 1131 patients had >1 year of data available to assess oncologic and cosmesis outcomes. Median age was 59 years old (range 22-90 years). Histologies treated included 1005 (73 %) invasive ductal carcinoma and 240 (18 %) ductal carcinoma-in situ. T stages were 18 % Tis, 75 % T1, and 8 % ≥T2. Nodal status was 73 % N0 and 6 % N1a. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was positive in 83, 70, and 6 %, respectively. Cox multivariate analysis for local control was performed using histology, age, estrogen receptor status, tumor size, grade, margin, and nodal status.

RESULTS: The mean (SD) follow-up was 6.9 years (4.3). The 10-year actuarial risk (95 % confidence interval) of an ipsilateral breast tumor recurrence was 7.6 % (5.6-10.1). Other 10-year actuarial risks (95 % confidence interval) were regional failure 2.3 % (1.4-3.7), distant metastasis 3.8 % (2.5-5.7), cause-specific survival 96.3 % (94.2-97.6), overall survival 86.5 (83.0-89.3), and new contralateral cancers 4.6 % (3.0-6.9). On multivariate analysis, high grade (hazard ratio 2.81) and positive margin status (hazard ratio 18.42) were the only two significant variables associated with an increased risk of local recurrence. Physician-reported cosmesis was excellent/good in 84 % (98 of 116) of patients with >5 years of follow-up.

CONCLUSIONS: This is the largest report of outcomes with interstitial breast brachytherapy. This treatment resulted in excellent long-term local control and cosmesis outcomes.}, } @article {pmid25915467, year = {2015}, author = {Nakash, O and Nagar, M and Kanat-Maymon, Y}, title = {"What should we talk about?" The association between the information exchanged during the mental health intake and the quality of the working alliance.}, journal = {Journal of counseling psychology}, volume = {62}, number = {3}, pages = {514-520}, doi = {10.1037/cou0000074}, pmid = {25915467}, issn = {0022-0167}, mesh = {Adult ; Attitude of Health Personnel ; *Communication ; Cooperative Behavior ; Female ; Health Personnel/*psychology ; Humans ; Israel/epidemiology ; Male ; *Mental Health ; Middle Aged ; *Professional-Patient Relations ; Psychology/methods/*standards ; Quality of Life/*psychology ; }, abstract = {We investigated the association between the content of the information exchanged between clients and therapists during mental health intake and the quality of the therapeutic alliance. Thirty-eight therapists and 107 clients from four mental health clinics in Israel participated in the study. The content of information discussed was coded directly from the recorded intakes by blinded raters. Clients and therapists completed the Working Alliance Inventory immediately following the intake. Therapists spent the majority of intake time in collecting information about their clients' diagnostic symptoms and personal history and sociocultural background. Due to the high negative correlation between these factors, r(107) = -.68, p < .001, we created a measure of delta score with higher scores reflecting more discussion of personal history and sociocultural background and less discussion of diagnostic symptoms. We computed three-level hierarchical linear model analysis, with intakes nested within therapists and therapists nested within sites, to examine the association between the delta score and the working alliance, while controlling for intake duration. Results showed significant association between the delta score and clients' rating of the working alliance (γ200 = 0.014, p = .02), indicating that discussing more personal history and sociocultural background and less diagnostic symptoms was associated with better clients' rating of the working alliance. Therapists' rating of the working alliance was not significantly associated with the content of the information exchanged. The restricted intake time allocated to therapists dictates use of strategies to deal with time trade-offs to complete a thorough diagnostic assessment while allowing clients to tell their personal story.}, } @article {pmid25913287, year = {2015}, author = {Spano, JP and Beuzeboc, P and Coeffic, D and Arnould, L and Lortholary, A and Andre, F and Ferrero, JM}, title = {Long term HER2+ metastatic breast cancer survivors treated by trastuzumab: Results from the French cohort study LHORA.}, journal = {Breast (Edinburgh, Scotland)}, volume = {24}, number = {4}, pages = {376-383}, doi = {10.1016/j.breast.2015.02.035}, pmid = {25913287}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Breast Neoplasms/chemistry/*drug therapy/mortality/pathology ; Disease-Free Survival ; Docetaxel ; Female ; Follow-Up Studies ; France ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration & dosage ; Prospective Studies ; Receptor, ErbB-2 ; Retrospective Studies ; *Survivors ; Taxoids/administration & dosage ; Trastuzumab/*administration & dosage ; }, abstract = {PURPOSE: The LORHA study described the clinical features of patients and tumours in long-term responders from a subset of breast cancer patients who responded to 1st-line trastuzumab and without disease progression.

METHODS: This was an ambispective, multicentre, non-interventional study conducted in 57 centres in France. Eligible patients were women with HER2+metastatic or locally-advanced breast cancer, treated with 1st-line therapy, progression-free for ≥3 years after starting trastuzumab, and followed-up for 12 months.

RESULTS: 160 patients were recruited, 128 were included in the efficacy analysis subset (median age: 61 years; [34-95 years]). A majority (88%) had invasive ductal carcinoma; 53% had SBR grade III carcinoma, and 58% were positive for hormonal receptors. The median time since diagnosis was 8 years [3-26 years]. The most frequent metastatic sites were the bone, liver, lymph nodes, and lungs in 43%, 35%, 20% and 19% of patients, respectively. The median duration of 1st-line trastuzumab was 4.5 years [0.8-12.1], combined with paclitaxel and docetaxel in 35 and 72 patients, respectively. Median PFS (progression-free survival) was 6.4 years [5.7; Not Reached]. No trastuzumab-related deaths were observed. In the safety analysis subset (N = 134), 3 cardiac adverse events considered related to trastuzumab were recorded in 3 patients (2.2%), and only one prospective congestive cardiac failure was of grade ≥3.

CONCLUSIONS: The LORHA study showed that long term responders to 1st-line trastuzumab for locally advanced or metastatic breast cancer could achieve a median PFS of more than 6 years, with an acceptable safety profile.}, } @article {pmid25911756, year = {2015}, author = {Miki, H and Nakahashi-Oda, C and Sumida, T and Shibuya, A}, title = {Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant-Induced Th2 Responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {194}, number = {11}, pages = {5069-5076}, doi = {10.4049/jimmunol.1402915}, pmid = {25911756}, issn = {1550-6606}, mesh = {Adjuvants, Immunologic/*pharmacology ; Alum Compounds/*pharmacology ; Animals ; Antibodies, Neutralizing/administration & dosage/immunology ; Apoptosis/immunology ; Asthma/genetics/immunology/therapy ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Dendritic Cells/immunology ; Eosinophils/immunology ; Immunoglobulin E/blood ; Inflammation/immunology ; Interleukin-4/biosynthesis ; Lymphocyte Activation/drug effects/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/*pharmacology ; Phosphatidylserines/antagonists & inhibitors ; Receptors, Immunologic/biosynthesis/genetics/*immunology ; Respiratory Hypersensitivity/genetics/*immunology/prevention & control ; Th2 Cells/*immunology ; }, abstract = {Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial. In an experimental allergic airway inflammation model, in which alum in conjunction with OVA Ag was i.p. injected for immunization, we found that apoptotic cells and inflammatory dendritic cells (iDC) expressing CD300a, an inhibitory immunoreceptor for phosphatidylserine (PS), significantly increased in number in the peritoneal cavity after the immunization. In contrast, apoptotic cells and iDCs were scarcely observed in the peritoneal cavity after injection of OVA alone. In CD300a-deficient mice, eosinophil infiltration in bronchoalveolar lavage fluid, serum IgE levels, and airway hyperreactivity were significantly decreased after immunization with alum plus OVA compared with wild-type mice. In vitro, iDCs purified from CD300a-deficient mice after the immunization induced significantly less IL-4 production from OT-II naive CD4(+) T cells after coculture with OVA Ag. CD300a expressed on iDCs bound PS on apoptotic cells in the peritoneal cavity after injection of OVA plus alum. Blocking CD300a interaction with PS by injection of a neutralizing anti-CD300a Ab resulted in inhibition of the development of allergic airway inflammation. These results suggest that CD300a is involved in alum-induced Th2 skewing.}, } @article {pmid25909142, year = {2015}, author = {Popovska, S and Damianova, P and Tomov, S and Dineva, T and Ivanov, I}, title = {[Case of encapsulated solid papillary carcinoma with triple-negative and basal-like phenotype occurred in pregnant woman with review of the literature].}, journal = {Akusherstvo i ginekologiia}, volume = {54}, number = {2}, pages = {50-56}, pmid = {25909142}, issn = {0324-0959}, mesh = {Adult ; BRCA1 Protein/analysis/genetics ; BRCA2 Protein/analysis/genetics ; Breast/*pathology ; Breast Neoplasms/diagnosis/genetics/*pathology ; Carcinoma, Papillary/diagnosis/genetics/*pathology ; Female ; Humans ; Mutation ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/genetics/*pathology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {The term breast cancer in pregnant women is used when the disease has been diagnosed during pregnancy or within first 12 months after delivery. The frequency of this type of breast cancer is about 7% of all cases in reproductive period. We present a case of breast cancer that occurred in pregnant 35 year old woman. We performed histological and immunohistochemical tests of excised tumor formation. We did not find sufficient evidence of both carcinoma in situ and invasive ductal carcinoma. The lesion was consisted with encapsulated/intracystic carcinoma, solid papillary variant with a low degree of differentiation-G3. Young age of patient, receptor status of the tumor the characteristic morphology of hereditary cancer, the presence of inflammatory infiltrates intratumorally, absence of reaction to IHC protein product of the tumor suppressor gene BRCA1 in combination with a positive p53 IHC makes this case suitable for genetic testing of BRCA1/BRCA2 susceptibility genes. The case is interesting because of the rarity of the histological variant, the young age of the patient, the combination with BC and pregnancy and the triple-negative phenotype.}, } @article {pmid25908223, year = {2015}, author = {del Molino, F and Gonzalez, I and Saperas, E}, title = {[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].}, journal = {Gastroenterologia y hepatologia}, volume = {38}, number = {8}, pages = {501-510}, doi = {10.1016/j.gastrohep.2015.02.014}, pmid = {25908223}, issn = {0210-5705}, mesh = {Administration, Oral ; Antithrombins/administration & dosage/*adverse effects/pharmacokinetics/therapeutic use ; Blood Coagulation Factors/therapeutic use ; Blood Transfusion ; *Endoscopy, Digestive System/adverse effects ; Factor Xa Inhibitors/administration & dosage/adverse effects/pharmacokinetics/therapeutic use ; Gastrointestinal Hemorrhage/*chemically induced/drug therapy/etiology/therapy ; Hemostatics/therapeutic use ; Humans ; Plasma Substitutes/therapeutic use ; Practice Guidelines as Topic ; Renal Dialysis ; Thrombophilia/drug therapy ; }, abstract = {New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed.}, } @article {pmid25905968, year = {2015}, author = {Mango, VL and Kaplan, J and Sung, JS and Moskowitz, CS and Dershaw, DD and Morris, EA}, title = {Breast carcinoma in augmented breasts: MRI findings.}, journal = {AJR. American journal of roentgenology}, volume = {204}, number = {5}, pages = {W599-604}, doi = {10.2214/AJR.14.13221}, pmid = {25905968}, issn = {1546-3141}, mesh = {Adult ; Aged ; Biopsy ; *Breast Implants ; Breast Neoplasms/*diagnosis/pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Mammaplasty ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: The objective of our study was to characterize the MRI features of breast carcinomas detected in augmented breasts.

MATERIALS AND METHODS: A review of the MRI database identified 54 patients with biopsy-proven breast carcinoma in augmented breasts. The images were reviewed for the type and location of the implant and for the characteristics of the carcinoma. The cases included 46 (85%) invasive cancers (invasive ductal carcinoma, n = 35; invasive lobular carcinoma, n = 7; and mixed features, n = 4) and eight (15%) ductal carcinomas in situ.

RESULTS: The median age of the patients at diagnosis was 49 years (range, 28-72 years). Thirty-eight of the 54 cancers (70%) were palpable. The mean tumor size was 2.8 cm (range, 0.6-9.6 cm). Of the 54 cancers, 34 (63%) presented as masses and 20 (37%) as nonmass enhancement on MRI. There was no detectable difference between implant position and lesion morphology (p = 0.55) or tumor size (p = 1.00). Twenty of 54 (37%) carcinomas abutted the implant, 13 (24%) abutted the pectoralis major muscle, and two (4%) invaded the pectoralis major muscle. Of the tumors abutting the implant, 18 of 20 (90%) spread along the implant capsule for more than 0.5 cm. This pattern of tumor spread was more common in breasts with retroglandular implants (9/16, 56%) than in those with retropectoral implants (9/38, 24%) (p = 0.03). MRI detected the index carcinoma in 16 of 54 (30%) cases, showed a greater extent of disease than was visible on mammography or ultrasound in 21 of 52 (40%) cases, and detected an unsuspected contralateral carcinoma in three of 54 (6%) cases.

CONCLUSION: In augmented breasts, breast cancer often contacts either the implant or the pectoralis major muscle. Tumor spread along the implant contour is more often seen with retroglandular implants than with retropectoral implants. MRI should be considered to assess disease extent in women with augmented breasts before surgery.}, } @article {pmid25905948, year = {2015}, author = {Poplack, SP and Levine, GM and Henry, L and Wells, WA and Heinemann, FS and Hanna, CM and Deneen, DR and Tosteson, TD and Barth, RJ}, title = {A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection.}, journal = {AJR. American journal of roentgenology}, volume = {204}, number = {5}, pages = {1100-1108}, pmid = {25905948}, issn = {1546-3141}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; CA23108/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Algorithms ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Contrast Media ; Cryosurgery/*methods ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Pilot Projects ; Prospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; *Ultrasonography, Interventional ; }, abstract = {OBJECTIVE: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation.

SUBJECTS AND METHODS: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility. Clinical status was evaluated at 1 day, 7-10 days, and 2 weeks after ablation. CE-MRI was performed 25-40 days after ablation, followed by surgical resection within 5 days.

RESULTS: Ultrasound-guided cryoablation was uniformly technically successful, and postablation clinical status was good to excellent in all participants. Cryoablation was not clinically successful in 15% (three of 20 patients). Three participants had residual cancer at the periphery of the cryoablation site. Two participants had viable nonmalignant tissue within the central zone of cryoablation-induced necrosis. Postablation CE-MRI had a sensitivity of 0% (0/3) and specificity of 88% (15/17). The predictive value of negative findings on CE-MRI was 83% (15/18). Correlations between cancer characteristics, cryoablation procedural variables, postablation CE-MRI findings, and surgical specimen features were not statistically significant. There were also no significant differences in participants with or without residual cancer.

CONCLUSION: In our pilot experience, ultrasound-guided cryoablation of invasive ductal carcinomas up to 15 mm has a clinical failure rate of 15% but is technically feasible and well tolerated by patients. The majority of cryoablation failures are manifest as DCIS outside the cryoablation field. Postablation CE-MRI does not reliably predict cryoablation outcome.}, } @article {pmid25905435, year = {2015}, author = {Tan, KK and Giam, CS and Leow, MY and Chan, CW and Yim, EK}, title = {Differential cell adhesion of breast cancer stem cells on biomaterial substrate with nanotopographical cues.}, journal = {Journal of functional biomaterials}, volume = {6}, number = {2}, pages = {241-258}, pmid = {25905435}, issn = {2079-4983}, abstract = {Cancer stem cells are speculated to have the capability of self-renewal and re-establishment of tumor heterogeneity, possibly involved in the potential relapse of cancer. CD44+CD24-/lowESA+ cells have been reported to possess tumorigenic properties, and these biomarkers are thought to be highly expressed in breast cancer stem cells. Cell behavior can be influenced by biomolecular and topographical cues in the natural microenvironment. We hypothesized that different cell populations in breast cancer tissue exhibit different adhesion characteristics on substrates with nanotopography. Adhesion characterizations were performed using human mammary epithelial cells (HMEC), breast cancer cell line MCF7 and primary invasive ductal carcinoma (IDC) cells obtained from patients' samples, on micro- and nano-patterned poly-L-lactic acid (PLLA) films. Topography demonstrated a significant effect on cell adhesion, and the effect was cell type dependent. Cells showed elongation morphology on gratings. The CD44+CD24-/lowESA+ subpopulation in MCF7 and IDC cells showed preferential adhesion on 350-nm gratings. Flow cytometry analysis showed that 350-nm gratings captured a significantly higher percentage of CD44+CD24- in MCF7. A slightly higher percentage of CD44+CD24-/lowESA+ was captured on the 350-nm gratings, although no significant difference was observed in the CD44+CD24-ESA+ in IDC cells across patterns. Taken together, the study demonstrated that the cancer stem cell subpopulation could be enriched using different nanopatterns. The enriched population could subsequently aid in the isolation and characterization of cancer stem cells.}, } @article {pmid25903462, year = {2015}, author = {Kubackova, K and Melichar, B and Bortlicek, Z and Pavlik, T and Poprach, A and Svoboda, M and Lakomy, R and Vyzula, R and Kiss, I and Dusek, L and Prausova, J and Buchler, T and , }, title = {Comparison of Two Prognostic Models in Patients with Metastatic Renal Cancer Treated with Sunitinib: a Retrospective, Registry-Based Study.}, journal = {Targeted oncology}, volume = {10}, number = {4}, pages = {557-563}, pmid = {25903462}, issn = {1776-260X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Renal Cell/*drug therapy/pathology ; Disease-Free Survival ; Female ; Humans ; Indoles/*therapeutic use ; Kidney Neoplasms/*drug therapy/pathology ; Male ; Middle Aged ; *Models, Statistical ; Neoplasm Metastasis ; Prognosis ; Pyrroles/*therapeutic use ; Registries ; Retrospective Studies ; Sunitinib ; Treatment Outcome ; }, abstract = {BACKGROUND: The study aimed to compare two prognostic models in terms of progression-free survival (PFS), median overall survival (OS), and 1-year survival in patients treated first-line with sunitinib for metastatic renal cell carcinoma (mRCC).

METHODS: Data from patients who met prognostic model criteria for recording of baseline parameters and outcomes in the Czech Patient Registry RENal Information System (RENIS) were included in the retrospective analysis (n = 495). Performance of the modified Memorial Sloan Kettering Cancer Center (MSKCC) model and International Database Consortium (IDC) model was compared. PFS and OS were estimated using the Kaplan-Meier method. The statistical significance of differences in Kaplan-Meier estimates was assessed using the log-rank test.

RESULTS: Median OS for prognostic groups according to MSKCC and IDC criteria, respectively, was 39.5 months (95 % confidence interval [CI]: 23.9-55.2) versus 44.3 months (95 % CI: 31.6-56.9) for favourable-risk patients (no adverse factors), 28.5 months (95 % CI: 20.1-36.8) versus 24.8 months (95 % CI: 19.8-29.8) for intermediate-risk patients (1-2 adverse factors), and 10.6 months (95 % CI: 6.3-14.8) versus 9.3 months (95 % CI: 5.1-13.5) for poor-risk patients (≥3 adverse factors). The majority of MSKCC poor-risk patients (54.1 %, n = 72) were reclassified as intermediate-risk using IDC criteria, and 20.2 % (n = 61) of MSKCC intermediate-risk patients were reclassified to the IDC favourable-risk group.

CONCLUSIONS: Both prognostic models were validated in the present cohort. Use of the IDC model resulted in an upward shift in prognostic assessment compared to the MSKCC model.}, } @article {pmid25900029, year = {2015}, author = {Zhifu, Y and Mingli, J and Shuang, C and Fan, W and Zhenkun, F and Wangyang, C and Lin, Z and Guangxiao, L and Yashuang, Z and Dianjun, L}, title = {SNP-SNP interactions of immunity related genes involved in the CD28/B7 pathway with susceptibility to invasive ductal carcinoma of the breast.}, journal = {Gene}, volume = {566}, number = {2}, pages = {217-222}, doi = {10.1016/j.gene.2015.04.044}, pmid = {25900029}, issn = {1879-0038}, mesh = {Algorithms ; Breast Neoplasms/genetics/*immunology ; CD28 Antigens/*immunology ; Carcinoma, Ductal, Breast/genetics/*immunology ; Cross-Over Studies ; Female ; *Genetic Predisposition to Disease ; Haplotypes ; Humans ; Immunity/*genetics ; *Polymorphism, Single Nucleotide ; }, abstract = {To explore the interactions among immunity related genes and the risk of breast cancer (BC), 376 invasive ductal carcinoma (IDC) of the breast cases and 366 healthy controls were selected into our study. Twenty single nucleotide polymorphisms (SNPs) of five immunological genes in the CD28/B7 pathway were genotyped. Overall, five SNPs filtered by the Relief F algorithm were rs733618, rs11889031, rs4553808, rs4675374 and rs10754339. The best model of multifactor dimensionality reduction (MDR) contained rs733618 and rs11889031. The high risk genotype combination contributed to increasing risk of breast cancer (odds ratio (OR), 4.36; 95% confidence interval (CI); 3.15-6.02). The information gain (IG) value of these two SNPs was 8.07%, presented the strongest interaction effect. Five significant multiplicative interactions and seven significant combining effects were found among the filtered SNPs. Moreover, the filtered SNPs were still stable in the groups of ER(+), PR(+), CerbB2(-) and lymph node (LN) involvement positive with the best models including rs733618 and rs11889031. The most frequent haplotype was TACC which significantly increased breast cancer risk (OR, 1.80; 95% CI, 1.43-2.25). These results suggested that interactions among cytotoxic T lymphocyte antigen-4 (CTLA4), inducible co-stimulator (ICOS) and B7H4 might play critical roles on the risk of breast cancer.}, } @article {pmid25899545, year = {2015}, author = {Amboni, M and Stocchi, F and Abbruzzese, G and Morgante, L and Onofrj, M and Ruggieri, S and Tinazzi, M and Zappia, M and Attar, M and Colombo, D and Simoni, L and Ori, A and Barone, P and Antonini, A and , }, title = {Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.}, journal = {Parkinsonism & related disorders}, volume = {21}, number = {6}, pages = {644-649}, doi = {10.1016/j.parkreldis.2015.03.028}, pmid = {25899545}, issn = {1873-5126}, mesh = {Aged ; Aged, 80 and over ; Antiparkinson Agents/administration & dosage/therapeutic use ; Female ; *Freezing Reaction, Cataleptic ; *Gait ; Gait Disorders, Neurologic/classification/*epidemiology/physiopathology ; Humans ; Levodopa/administration & dosage/therapeutic use ; Male ; Middle Aged ; Parkinson Disease/drug therapy/*physiopathology/psychology ; Prevalence ; Quality of Life/*psychology ; Risk Factors ; Self Report ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity.}, } @article {pmid25893606, year = {2015}, author = {Zhou, X and Wang, S and Wang, Z and Feng, X and Liu, P and Lv, XB and Li, F and Yu, FX and Sun, Y and Yuan, H and Zhu, H and Xiong, Y and Lei, QY and Guan, KL}, title = {Estrogen regulates Hippo signaling via GPER in breast cancer.}, journal = {The Journal of clinical investigation}, volume = {125}, number = {5}, pages = {2123-2135}, pmid = {25893606}, issn = {1558-8238}, mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/physiology ; Animals ; Breast Neoplasms/genetics/metabolism/*physiopathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*physiopathology ; Cell Division ; Cell Movement ; Cell Transformation, Neoplastic ; Estrogens/pharmacology/*physiology ; Female ; GTP-Binding Protein alpha Subunits, Gq-G11/antagonists & inhibitors/genetics/physiology ; Gene Expression Regulation, Neoplastic ; Hippo Signaling Pathway ; Humans ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Inbred BALB C ; Neoplasm Proteins/*physiology ; Neoplasms, Hormone-Dependent/genetics/metabolism/*physiopathology ; Phospholipase C beta/physiology ; Phosphoproteins/physiology ; Phosphorylation ; Protein Kinase C/physiology ; Protein Processing, Post-Translational ; Protein Serine-Threonine Kinases/analysis/antagonists & inhibitors/metabolism/*physiology ; RNA Interference ; Receptors, Estrogen/drug effects/*physiology ; Receptors, G-Protein-Coupled/drug effects/*physiology ; Serine-Threonine Kinase 3 ; Signal Transduction/*physiology ; Transcription Factors/physiology ; Transcription, Genetic ; Tumor Suppressor Proteins/analysis/*physiology ; YAP-Signaling Proteins ; rho-Associated Kinases/physiology ; }, abstract = {The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.}, } @article {pmid25893590, year = {2015}, author = {Zhang, H and Li, Y and Moran, MS and Haffty, BG and Yang, Q}, title = {Predictive factors of nipple involvement in breast cancer: a systematic review and meta-analysis.}, journal = {Breast cancer research and treatment}, volume = {151}, number = {2}, pages = {239-249}, doi = {10.1007/s10549-015-3385-4}, pmid = {25893590}, issn = {1573-7217}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*mortality ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nipples/*pathology ; Prognosis ; Risk Factors ; Tumor Burden ; }, abstract = {Nipple-sparing mastectomy (NSM) provides a cosmetic and psychological benefit for patients, but concerns on nipple involvement (NI) of tumor continue to persist. Several studies have reported factors for predicting NI, but the results were inconsistent and uncomprehensive, making patient selection difficult. The aim of the systematic review was to pool the published data to further discern factors associated with NI. A literature review was conducted of PubMed database, following the PRISMA guidelines. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effect or fix-effect model. Publication bias and Chi-square test were also calculated. From 1978 to 2014, 27 clinical studies with 7971 patients met the inclusion criteria. Predictive factors suggest higher rates of NI including the following: tumor-to-nipple distance (TND) ≤ 2.5 cm (3.65, 1.42-9.33); positive lymph node status (2.09, 1.71-2.57); stage III or IV disease (2.41, 1.93-3.00); tumor size > 5 cm (2.42, 1.95-3.02); estrogen receptor (ER)-negative status (1.19, 1.01-1.40); progesterone receptor (PR)-negative status (1.52, 1.25-1.84); HER-positive status (1.76, 1.46-2.12); patients with ductal carcinoma in situ (DCIS) compared with invasive ductal carcinoma (1.55, 1.16-2.08). Due to the statistical heterogeneity detected with certain parameters, further investigations to confirm their association with NI will be needed. Patients with one or more risk factors such as centrally located tumors; higher tumor stage; large tumors; ER-negative/PR-negative/HER-positive status and associated DCIS have higher risk of NI. Taking these factors into consideration comprehensively may help with decision-making process for NSM.}, } @article {pmid25890786, year = {2015}, author = {Sugiyama, M and Hasebe, T and Shimada, H and Takeuchi, H and Shimizu, K and Shimizu, M and Yasuda, M and Ueda, S and Shigekawa, T and Osaki, A and Saeki, T}, title = {Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.}, journal = {Human pathology}, volume = {46}, number = {6}, pages = {906-916}, doi = {10.1016/j.humpath.2015.03.001}, pmid = {25890786}, issn = {1532-8392}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Vascular Tissue/*pathology/secondary ; Neoplastic Cells, Circulating/pathology ; Prognosis ; }, abstract = {We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast.}, } @article {pmid25890610, year = {2015}, author = {Debi, U and Thulkar, S and Sharma, S and Sharma, MC and Seenu, V and Deo, SV and Agarwal, S and Hari, S}, title = {Role of directional vacuum assisted breast biopsy in previously equivocal biopsies for breast masses suspicious for malignancy.}, journal = {The Malaysian journal of pathology}, volume = {37}, number = {1}, pages = {25-33}, pmid = {25890610}, issn = {0126-8635}, mesh = {Biomarkers, Tumor/analysis ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/chemistry/*pathology/secondary/surgery ; Breast Neoplasms, Male/chemistry/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Male ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Reproducibility of Results ; Vacuum ; }, abstract = {UNLABELLED: Among percutaneous biopsy techniques, the vacuum assisted breast biopsy (VAB) obtains large tissue samples to alleviate some of the limitations associated with conventional percutaneous biopsy techniques. We aimed to determine the efficacy of VAB in previous equivocal biopsies using the mammotome device.

MATERIALS AND METHODS: A prospective non-randomized efficacy study was planned and executed on 43 patients (42 women, 1 man) whose previous FNAC and/or CNB of breast masses yielded inconclusive results or were suspicious for cancer.

RESULTS: VAB revealed malignancy in 31 (72%) of the 43 patients. Among them, 23 were diagnosed as infiltrative ductal carcinoma (IDC) on VAB, 20 underwent surgery and the final histopathological diagnosis was the same in 19 of them. One patient showed ductal carcinoma-in-situ (DCIS) only in the surgical specimen. Other malignancies included infiltrating lobular carcinoma (ILC) in 5 patients and one each of DCIS, non- Hodgkin lymphoma (NHL) and metastasis from lung cancer. Benign lesions were detected in 12 (28%) patients. These included 8 fibroadenomas, 2 fibrocystic disease and 1 each of mastitis and breast abscess. Four patients with fibroadenoma underwent surgical excision.}, } @article {pmid25889560, year = {2015}, author = {Jung, NY and Kim, SH and Choi, BB and Kim, SH and Sung, MS}, title = {Associations between the standardized uptake value of (18)F-FDG PET/CT and the prognostic factors of invasive lobular carcinoma: in comparison with invasive ductal carcinoma.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {113}, pmid = {25889560}, issn = {1477-7819}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnostic imaging/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/*pathology/surgery ; Carcinoma, Lobular/diagnostic imaging/metabolism/*pathology/surgery ; ErbB Receptors/metabolism ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Positron-Emission Tomography/*methods ; Prognosis ; Radiopharmaceuticals/pharmacokinetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Tissue Distribution ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND: The aims of this study were to evaluate the associations between the maximum standardized uptake value (SUVmax) and prognostic factors in invasive lobular carcinoma (ILC) and to compare these results with those in invasive ductal carcinoma (IDC).

METHODS: The study included pathologically confirmed ILCs (n = 32) and IDCs (n = 73). We retrospectively evaluated the preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and measured the SUVmax. The pathologic results were reviewed regarding the size, histological type, histological grade, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and Ki-67 of the primary tumor. We also compared the associations between the SUVmax and prognostic factors.

RESULTS: The mean SUVmax of the ILCs was significantly lower compared with that of the IDCs (P = 0.032). The SUVmax increased with tumor grade (P < 0.001) and was higher with ER negativity compared with ER positivity (P = 0.007) in IDC. The SUVmax was higher with EGFR positivity compared with EGFR negativity (P = 0.013) in IDC and higher with Ki-67 positivity compared with Ki-67 negativity in IDC and ILC (P < 0.001 and P = 0.002, respectively). The SUVmax was not significantly different regarding PR or HER2 for both tumor groups. The correlation between the tumor size and the SUVmax was demonstrated for IDCs (r = 0.57), but not for ILCs (r = 0.25).

CONCLUSIONS: The SUVmax was significantly different according to the tumor grade, ER, EGFR, and Ki-67 for IDCs. The SUVmax exhibited a positive association with Ki-67 in ILC; however, it was not significantly different with other factors, which suggests that the role of (18)F-FDG PET/CT may be limited in ILC.}, } @article {pmid25889325, year = {2015}, author = {Han, Z and Chen, Z and Zheng, R and Cheng, Z and Gong, X and Wang, D}, title = {Clinicopathological significance of CD133 and CD44 expression in infiltrating ductal carcinoma and their relationship to angiogenesis.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {56}, pmid = {25889325}, issn = {1477-7819}, mesh = {AC133 Antigen ; Adult ; Aged ; Antigens, CD ; Breast Neoplasms/blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*secondary ; Female ; Follow-Up Studies ; Glycoproteins ; Humans ; Hyaluronan Receptors ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism/*pathology ; Neovascularization, Pathologic/metabolism/*pathology ; Peptides ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the leading cause of cancer death in females worldwide, and the majority type is infiltrating ductal carcinoma (IDC). Most of IDC patients died of metastasis and recurrence. Cancer stem cells (CSCs) are defined with the ability to be self-renewal and potentially promote proliferation and formation of tumors. CSCs are related to angiogenesis and are important targets in new cancer treatment strategies. In this study, we purposed to investigate on expression and clinical significances of CSCs marked by CD133 and CD44 in IDC and their relationship to angiogenesis.

METHODS: The specimens of IDC from 325 Chinese patients with follow-up were analyzed for CD133, CD44, CD82, and CD34 protein expression by immunohistochemical staining. The Pearson chi-square test and t test were used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time in these patients with IDC was analyzed by univariate and multivariate analyses.

RESULTS: In IDC tissues, positive rates of 48.6%, 53.8%, and 42.2% were obtained for CD133, CD44, and CD82 protein, respectively; the mean score of microvessel density (MVD) was 20.5 ± 7.0 in IDC group. And there was a significant difference between the two groups. There was a positive relationship between the expression of CD133, CD44, and the score of MVD and the grades of tumor, lymph node metastasis, tumor-node-metastasis (TNM) stages (all P < 0.05); and the expression of CD82 was negatively related to grades of tumor, lymph node metastasis, and TNM stages (all P < 0.05). The overall mean survival time of the patients with CD133, CD44, and the score of MVD (≥21) positive expression was lower than that of patients with negative expression. The overall mean survival time of patients of CD82-positive expression was longer than that of patients of the negative expression group. The positive expression of CD133 and CD82, and TNM stages were independent prognostic factors of IDC (P < 0.05).

CONCLUSIONS: CSCs, angiogenesis, and aberrant expression of CD82 may be involved in the initiation, development, metastasis, and recurrence. It is suggested that CSCs, angiogenesis, and CD82 be possible as a therapeutic marker for anti-tumor therapy.}, } @article {pmid25888835, year = {2015}, author = {Nakahori, R and Takahashi, R and Akashi, M and Tsutsui, K and Harada, S and Matsubayashi, RN and Nakagawa, S and Momosaki, S and Akagi, Y}, title = {Breast carcinoma originating from a silicone granuloma: a case report.}, journal = {World journal of surgical oncology}, volume = {13}, number = {}, pages = {72}, pmid = {25888835}, issn = {1477-7819}, mesh = {Aged ; Breast Implants/*adverse effects ; Breast Neoplasms/*etiology/pathology ; Carcinoma, Ductal, Breast/*etiology/pathology ; Female ; Granuloma, Foreign-Body/*etiology ; Humans ; Prognosis ; Silicones/*adverse effects ; }, abstract = {Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.}, } @article {pmid25887149, year = {2015}, author = {Barranger, E and Antomarchi, J and Chamorey, E and Cavrot, C and Flipo, B and Follana, P and Peyrottes, I and Chapellier, C and Ferrero, JM and Ihrai, T}, title = {Effect of Neoadjuvant Chemotherapy on the Surgical Treatment of Patients With Locally Advanced Breast Cancer Requiring Initial Mastectomy.}, journal = {Clinical breast cancer}, volume = {15}, number = {5}, pages = {e231-5}, doi = {10.1016/j.clbc.2015.03.001}, pmid = {25887149}, issn = {1938-0666}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/surgery ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/*prevention & control ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this study was to assess the rate of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (nCT) in patients for whom mastectomy (MT) was, initially, the only conceivable surgical option.

PATIENTS AND METHODS: Between 2007 and 2012, 168 patients from a single center received nCT. Among these patients, we focused on the ones who received nCT (n = 119, [70.8%]) to decrease tumor size and thus to potentially allow a conservative surgical treatment. For these patients, MT was initially the only possible surgical treatment.

RESULTS: Among the 119 patients included, 118 presented with an invasive ductal carcinoma. The mean tumor size before nCT, measured using magnetic resonance imaging, was 41.6 mm (range, 15-110 mm) and 25.3 mm (range, 0-90 mm) after nCT. Eighty-six patients (72.3%) underwent BCS, and oncoplastic techniques were used in 29 patients (33.6%). Only 4.3% (5 patients) of patients who were treated with BCS needed additional surgery because of positive surgical margins. The median follow-up was 41.1 months (95% confidence interval [CI], 35.2-48.3). Five-year overall survival after BCS and MT were 77% (95% CI, 63-92) and 77% (95% CI, 63-95) respectively. Five-year disease-free survival after BCS and MT were 74% (95% CI, 64-86) and 59% (95% CI, 40-89) (not significant), respectively.

CONCLUSION: nCT for selective patients with "chemosensitive" breast tumor leads to a significant "MT to BCS" conversion rate. The type of surgery does not seem to affect the patient's overall and disease-free survival rates. Oncoplastic procedures can help to extend BCS after nCT.}, } @article {pmid25886700, year = {2015}, author = {An, YS and Kang, DK and Jung, YS and Han, S and Kim, TH}, title = {Tumor metabolism and perfusion ratio assessed by 18F-FDG PET/CT and DCE-MRI in breast cancer patients: Correlation with tumor subtype and histologic prognostic factors.}, journal = {European journal of radiology}, volume = {84}, number = {7}, pages = {1365-1370}, doi = {10.1016/j.ejrad.2015.03.026}, pmid = {25886700}, issn = {1872-7727}, mesh = {Adult ; Aged ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/diagnosis/*metabolism ; *Contrast Media ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Multimodal Imaging/methods ; Positron-Emission Tomography/*methods ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVE: Our purpose was to evaluate whether breast cancer with high metabolic-perfusion ratio would be associated with poor histopathologic prognostic factors and whether triple negative breast cancer (TNBC) would show high metabolic-perfusion ratio compared to non-triple negative breast cancer (non-TNBC).

METHODS: From March 2011 to November 2011, 67 females with invasive ductal carcinoma of breast who underwent both MRI and 18F-FDG PET/CT were included. Perfusion parameters including Ktrans, Kep and Ve were acquired from Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Metabolic parameters including the standardized uptake value (SUV) and volumetric metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT).

RESULTS: In non-TNBC, SUVmax was significantly correlated with Kep (ρ=0.298, p=0.036) and Ve (ρ=-0.286, p=0.044). In TNBC, there was no significant correlation between all perfusion and metabolic parameters. Compared to non-TNBC, higher SUVmax (10.2 vs 5.3, p<0.001), higher SUVmax/Ktrans (56.02 vs 20.3, p<0.001), higher MTV50/Ktrans (7.8 vs 16.54, p<0.001), higher TLG50/Ktrans (36.49 vs 12.3, p<0.001), higher TLG50/Ve (91.34 vs 27.1 p=0.022) were significantly correlated with TNBC. Lower Ktrans (0.17 vs 0.29, p=0.017) and lower Ve (0.29 vs 0.41, p=0.011) were also significantly associated TNBC.

CONCLUSION: While several perfusion parameters and metabolic parameters were correlated in non-TNBC, they were not correlated in TNBC. TNBC showed higher metabolic-perfusion ratios compared to non-TNBC.}, } @article {pmid25886372, year = {2015}, author = {Liu, D and Zhang, L and Li, Z and Zhang, X and Wu, Y and Yang, H and Min, B and Zhang, X and Ma, D and Lu, Y}, title = {Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease.}, journal = {BMC neurology}, volume = {15}, number = {}, pages = {14}, pmid = {25886372}, issn = {1471-2377}, mesh = {Aged ; Alzheimer Disease/*physiopathology ; Case-Control Studies ; Cognitive Dysfunction/*physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Retina/*pathology ; Tomography, Optical Coherence ; Vision Disorders/etiology ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls.

METHODS: The RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls.

RESULTS: The thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients.

CONCLUSIONS: Our data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments.}, } @article {pmid25881163, year = {2015}, author = {Barquet-Muñoz, SA and Villarreal-Colin, SP and Herrera-Montalvo, LA and Soto-Reyes, E and Pérez-Plasencia, C and Coronel-Martínez, J and Pérez-Montiel, D and Vázquez-Romo, R and Cantú de León, D}, title = {Metaplastic breast cancer: a comparison between the most common histologies with poor immunohistochemistry factors.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {75}, pmid = {25881163}, issn = {1471-2407}, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/mortality/*pathology/therapy ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Metaplasia ; Middle Aged ; Mortality ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Metaplastic carcinoma of the breast (MCB) is a rare histological type of breast cancer. This study aimed to determine whether MCB exhibits shorter overall survival (OS) and disease-free survival (DFS) compared with other histologies that are considered unfavorable.

METHODS: We retrospectively analyzed 157 clinical file records of the Mexico City-based National Institute of Cancerology and compared the clinical characteristics and treatment of 24 patients with MCB, 37 patients with triple-negative invasive lobular carcinoma (TN-ILC), 48 patients with high-grade invasive ductal carcinoma (HG-IDC), and 48 patients with triple-negative invasive ductal carcinoma (TN-IDC), paired by clinical stage and age. We performed a comparative analysis and analyzed OS and DFS using a log-rank test.

RESULTS: In patients with MCB, the 5-year DFS was 52.1% (mean, 48.52 months; 95%: 35.32-61.72), and the 5-year OS was 72.2% (mean, 59.77 months; 95% CI: 48.55-71.00). No differences were observed in the DFS of MCB compared with each of the other histologies (MCB vs. HG-IDC, p = 0.865; MCB vs. TN-IDC, p = 0.966, and MCB vs. TN-ILC, p = 0.132). Moreover, no differences were observed when comparing the OS of MCB with that of each of the other histologies (MCB vs. HG-IDC, p = 0.246; MCB vs. TN-IDC, p = 0.255, and MCB vs. TN-ILC, p = 0.387).

CONCLUSIONS: Neither OS nor DFS differ between patients with MCB and those with other histologies with unfavorable immunohistochemical factors.}, } @article {pmid25881005, year = {2015}, author = {Toyoshima, M and Iwahashi, H and Shima, T and Hayasaka, A and Kudo, T and Makino, H and Igeta, S and Matsuura, R and Ishigaki, N and Akagi, K and Sakurada, J and Suzuki, H and Yoshinaga, K}, title = {Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.}, journal = {Journal of medical case reports}, volume = {9}, number = {}, pages = {47}, pmid = {25881005}, issn = {1752-1947}, mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/diagnosis/*secondary/therapy ; Carrier Proteins/analysis ; Combined Modality Therapy ; Female ; Glycoproteins/analysis ; Humans ; Leiomyoma/therapy ; Membrane Transport Proteins ; Middle Aged ; Nitriles/therapeutic use ; Triazoles/therapeutic use ; Uterine Neoplasms/*secondary/therapy ; }, abstract = {INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma.

CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue.

CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.}, } @article {pmid25880415, year = {2015}, author = {Tancioni, I and Miller, NL and Uryu, S and Lawson, C and Jean, C and Chen, XL and Kleinschmidt, EG and Schlaepfer, DD}, title = {FAK activity protects nucleostemin in facilitating breast cancer spheroid and tumor growth.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {47}, pmid = {25880415}, issn = {1465-542X}, support = {R01 CA087038/CA/NCI NIH HHS/United States ; CA180769/CA/NCI NIH HHS/United States ; R01 CA102310/CA/NCI NIH HHS/United States ; CA102310/CA/NCI NIH HHS/United States ; R01 CA180769/CA/NCI NIH HHS/United States ; F32 CA159558/CA/NCI NIH HHS/United States ; 1F32CA159558/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Enzyme Activation ; Female ; Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/*metabolism ; GTP-Binding Proteins/*metabolism ; Humans ; Mice ; Nuclear Proteins/*metabolism ; Nucleophosmin ; Protein Kinase Inhibitors/pharmacology ; Protein Transport ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Sirolimus/pharmacology ; Spheroids, Cellular ; Tumor Burden/drug effects/genetics ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; }, abstract = {INTRODUCTION: Focal adhesion kinase (FAK) controls cell growth and survival downstream of integrin-matrix receptors. Upon adhesion loss or FAK inhibition, FAK can translocate to the nucleus. The nucleolus is a non-membrane nuclear structure that regulates ribosome biogenesis and cell proliferation. Nucleostemin (NS), a nucleolar-localized protein, modulates cell cycle progression, stemness, and three-dimensional tumor spheroid formation. The signaling pathways that regulate NS levels in tumors remain undefined.

METHODS: Human breast carcinoma cells were evaluated for growth in culture (adherent and anchorage-independent spheroid) and as orthotopic tumors. FAK signaling was evaluated by pharmacological FAK inhibitor addition (PF-271, IC50~0.1 μM) and by small hairpin RNA (shRNA) knockdown followed by re-expression of FAK wildtype (WT) or a kinase-dead (KD, K454R) FAK point mutant. Immunoblotting was used to evaluate FAK, NS, nucleolar phosphoprotein B23, and nucleolin levels. Total and phosphospecific antibody imunoblotting were used to detect changes in FAK, Akt kinase (Akt also known as protein kinase B), and 4E-binding protein 1 (4E-BP1) phosphorylation, a translation repressor protein and target of the mammalian target of rapamycin (mTOR) complex. Immunohistochemical, co-immunoprecipitation, and cellular fractionation analyses were used to evaluate FAK association with nucleoli.

RESULTS: Pharmacological (0.1 μM PF-271) or genetic inhibition of FAK activity prevents MDA-MB-231 and 4T1L breast carcinoma growth as spheroids and as orthotopic tumors. FAK inhibition triggers proteasome-mediated decreased NS levels but no changes in other nucleolar proteins such as B23 (nucleophosmin) or nucleolin. Active FAK was associated with purified nucleoli of anchorage-independent cells and present within nucleoli of human invasive ductal carcinoma tumor samples. FAK co-immunoprecipitated with B23 that binds NS and a complex between FAK, NS, Akt, and mTOR was detected. Constitutively-active Akt kinase promoted tumor spheroid growth, stabilized NS levels, and promoted pS65 4E-BP1 phosphorylation in the presence of inhibited FAK. Rapamycin lowered NS levels and inhibited pS65 4E-BP1 phosphorylation in cells with activated Akt-mTOR signaling.

CONCLUSIONS: FAK signaling occurs in the nucleolus, active FAK protects NS, and Akt-mTOR pathway regulates NS protein stability needed for breast carcinoma spheroid and tumor growth.}, } @article {pmid25880352, year = {2015}, author = {Benezet-Mazuecos, J and Iglesias, JA and Rubio, JM and Farré, J}, title = {Anodal Stimulation in Biventricular Pacing: Unrecognized and Misinterpreted Phenomenon.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {38}, number = {12}, pages = {1485-1488}, doi = {10.1111/pace.12650}, pmid = {25880352}, issn = {1540-8159}, mesh = {Aged, 80 and over ; Cardiac Resynchronization Therapy/*adverse effects/*methods ; Diagnosis, Differential ; Diagnostic Errors/*prevention & control ; Electric Injuries/*diagnosis/*etiology/prevention & control ; Heart Failure/complications/*prevention & control ; Humans ; }, } @article {pmid25880163, year = {2015}, author = {Zhang, Y and Ou, Y and Yu, D and Yong, X and Wang, X and Zhu, B and Zhang, Q and Zhou, L and Cai, Z and Cheng, Z}, title = {Clinicopathological study of centrally necrotizing carcinoma of the breast.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {282}, pmid = {25880163}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Necrosis ; Prognosis ; }, abstract = {BACKGROUND: Centrally necrotizing carcinoma of the breast (CNC) represents a newly-identified subset of breast cancer. The clinical and pathological characteristics of this breast cancer subtype are not yet completely understood.

METHODS: We assessed the clinicopathological characteristics of 73 cases of CNC and 30 control cases of high-grade infiltrating ductal carcinoma (IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor, progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor, cytokeratin 5/6, smooth muscle actin, S-100 protein, p63 and CD10.

RESULTS: All the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue which were usually high-grade IDCs. The central necrotic zone accounted for at least 30% of the cross-sectional area of the tumor. Thirty-six cases (49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases (40%). Lymphocytic infiltration was present in 53 cases (72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases (67.1%). Immunohistochemistry showed greater expression of basal-like markers (72.2%, 52 cases) than myoepithelial markers (60.6%, 43 cases), both of which were significantly higher than in controls (26.7%, 8 cases) (P < 0.001). According to molecular typing, most CNCs were basal-like subtype (37 cases, 50.7%). Follow-up data were available for 28 patients. Disease progression occurred in 11 patients. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls (P < 0.05).

CONCLUSIONS: CNC was associated with distinctive clinicopathologic features mostly characterized as basal-like type. Its high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis, suggest that CNC should be classified as a new type of breast carcinoma.}, } @article {pmid25880075, year = {2015}, author = {Bae, SY and Kim, S and Lee, JH and Lee, HC and Lee, SK and Kil, WH and Kim, SW and Lee, JE and Nam, SJ}, title = {Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer.}, journal = {BMC cancer}, volume = {15}, number = {}, pages = {138}, pmid = {25880075}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy/genetics/*metabolism/*mortality/pathology ; Female ; Follow-Up Studies ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Risk Factors ; Survival Analysis ; Triple Negative Breast Neoplasms/drug therapy/genetics/mortality ; Young Adult ; }, abstract = {BACKGROUND: Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. Generally, hormone receptor-positive (HR+) breast cancers have favorable prognosis. In order to understand the exact clinical characteristics and prognosis of single HR-positive breast cancer (ER + PR- tumors and ER-PR+ tumors), we compared these tumors to double HR+ tumors as well as HR- negative tumors (ER-PR-).

METHODS: We examined the clinical and biological features of 6,980 women with invasive ductal carcinoma, and these patients were stratified according to ER and PR expression as double HR+ (ER + PR+), single HR+ (ER + PR- and ER-PR+) and double HR-negative (HR-, ER-PR-) tumors.

RESULTS: In this study, 571 (8.2%) cases were single HR+ tumors, of which 90 (1.3%) were ER-PR+ tumors and 481 (6.9%) were ER + PR- tumors. Our multivariate analysis showed that in patients without HER2 overexpression ER + PR- tumors were associated with an increased risk of recurrence and death compared with ER + PR+ tumors, with a hazard ratio of 2.12 for disease-free survival (DFS) and 4.79 for overall survival (OS). In patients without HER2 overexpression ER-PR+ tumors had increased risk of recurrence and death compared with ER + PR+ tumor, with a hazard ratio of 4.19 for DFS and 7.22 for OS. In contrast, in patients with HER2 overexpression, the difference in survival between single HR+ tumors and double HR+ HR- tumors was not statistically significant. In patients without HER2 overexpression the DFS and OS of ER + PR- and ER-PR+ tumors were not significantly different from those of ER-PR- tumors.

CONCLUSION: We have identified clinically and biologically distinct features of single HR+ tumors (ER-PR+ and ER + PR-) through comparison with both ER + PR+ and ER-PR- tumors. These differences were only significant in HER2- tumors, not in HER2+ tumors. Single HR+ tumors without HER2 overexpression (ER + PR-HER2- or ER-PR + HER2-) were associated with poorer survival than ER + PR + HER2- tumors, and had comparable poor survival to ER-PR-HER2- tumors (triple-negative breast cancer).}, } @article {pmid25880063, year = {2015}, author = {Matsumura, Y and Hoshikawa-Nagai, E and Kubo, T and Yamasaki, N and Kitaoka, H and Takata, J and Doi, Y and Sugiura, T}, title = {Prediction of left ventricular reverse remodeling after therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and β blockers in patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular ultrasound}, volume = {13}, number = {}, pages = {14}, pmid = {25880063}, issn = {1476-7120}, mesh = {Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Cardiomyopathy, Dilated/*diagnostic imaging/*drug therapy/physiopathology ; Echocardiography/methods ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Recovery of Function/drug effects/physiology ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; Ventricular Remodeling/*drug effects/physiology ; }, abstract = {BACKGROUND: Predictors of left ventricular reverse remodeling (LVRR) after therapy with angiotensin converting enzyme inhibitors or angiotensin-receptor blockers and β blockers in patients with idiopathic dilated cardiomyopathy (IDC) remains unclear.

METHODS: We studied 44 patients with IDC who had been treated with the therapy. LVRR was defined as LV end-diastolic dimension ≤ 55 mm and fractional shortening ≥ 25% at the last echocardiogram.

RESULTS: During a mean follow-up period of 4.7 ± 3.3 years, LVRR occurred in 34% (15/44) of the patients. We divided the patients into 2 groups: (1) patients with LVRR (n = 15); (2) patients without LVRR (n = 29). The presence of atrial fibrillation was 40% in patients with LVRR and 14% in those without (p = 0.067). Initial LV end-diastolic dimension was significantly smaller (62 ± 6 vs. 67 ± 6 mm, p = 0.033) in patients with LVRR than in those without. Initial LV end-diastolic dimension of 63.5 mm was an optimal cutoff value for predicting LVRR (sensitivity: 67%, specificity: 59%, area under the curve: 0.70, p = 0.030). When patients were further allocated according to initial LV end-diastolic dimension ≤ 63.5 mm with atrial fibrillation, the combined parameter was a significant predictor of LVRR by univariate logistic regression analysis (odds ratio, 5.78, p = 0.030) (sensitivity: 33%, specificity: 97%, p = 0.013).

CONCLUSIONS: Combined information on LV end-diastolic dimension and heart rhythm at diagnosis is useful in predicting future LVRR in patients with IDC.}, } @article {pmid25873048, year = {2015}, author = {Takagi, K and Miki, Y and Nakamura, Y and Hirakawa, H and Kakugawa, Y and Amano, G and Watanabe, M and Ishida, T and Sasano, H and Suzuki, T}, title = {Immunolocalization of thymidylate synthase as a favorable prognostic marker in estrogen receptor-positive breast carcinoma.}, journal = {Histology and histopathology}, volume = {30}, number = {10}, pages = {1223-1232}, doi = {10.14670/HH-11-619}, pmid = {25873048}, issn = {1699-5848}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptors, Estrogen/*metabolism ; Thymidylate Synthase/*metabolism ; }, abstract = {BACKGROUND: Thymidylate synthase (TS) is an enzyme involved in DNA synthesis, and it is a target for 5-fluorouracil. Previous studies have demonstrated that TS is a potent estrogen-induced gene in breast carcinoma cells, suggesting the importance of TS in estrogen-receptor (ER)-positive breast carcinoma. TS immunolocalization has been reported previously, but the clinicopathological significance of TS in ER-positive breast carcinoma still remains unclear.

PATIENTS AND METHODS: We immunolocalized TS in 178 breast carcinoma tissues in total, and examined its significance according to the ER-status.

RESULTS: TS status was positive in 58% of ER-positive ductal carcinoma in situ (DCIS) cases, and it was significantly associated with the Ki-67 and progesterone receptor (PR). Moreover, in ER-positive DCIS patients who received aromatase inhibitor (AI) before surgery, TS immunoreactivity was significantly decreased after AI treatment. In ER-positive invasive ductal carcinoma (IDC) cases, TS status was significantly associated with PR, and it turned out an independent favorable prognostic factor for recurrence of the patients by multivariate analysis. On the other hand, TS status was positively correlated with pathological T factor in ER-negative IDC cases, and tended to have a worse prognosis for disease-free survival of the patients.

CONCLUSION: These results suggest that TS expression is mainly regulated by estrogen in ER-positive breast carcinoma and is associated with estrogen-mediated proliferation. TS status is a favorable prognostic factor in ER-positive IDC patients, which is different from the ER-negative cases.}, } @article {pmid25870386, year = {2016}, author = {Goldenberg, A and Halperin, E and van Zomeren, M and Gross, JJ}, title = {The Process Model of Group-Based Emotion: Integrating Intergroup Emotion and Emotion Regulation Perspectives.}, journal = {Personality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc}, volume = {20}, number = {2}, pages = {118-141}, doi = {10.1177/1088868315581263}, pmid = {25870386}, issn = {1532-7957}, mesh = {Emotional Intelligence ; *Emotions ; *Group Processes ; Humans ; Interpersonal Relations ; Models, Psychological ; }, abstract = {Scholars interested in emotion regulation have documented the different goals and strategies individuals have for regulating their emotions. However, little attention has been paid to the regulation of group-based emotions, which are based on individuals' self-categorization as a group member and occur in response to situations perceived as relevant for that group. We propose a model for examining group-based emotion regulation that integrates intergroup emotions theory and the process model of emotion regulation. This synergy expands intergroup emotion theory by facilitating further investigation of different goals (i.e., hedonic or instrumental) and strategies (e.g., situation selection and modification strategies) used to regulate group-based emotions. It also expands emotion regulation research by emphasizing the role of self-categorization (e.g., as an individual or a group member) in the emotional process. Finally, we discuss the promise of this theoretical synergy and suggest several directions for future research on group-based emotion regulation.}, } @article {pmid25859463, year = {2015}, author = {Swathy, PU and Arunalatha, P and Chandramouleeswari, K and Lily, SM and Ramya, S}, title = {Adenosquamous variant of metaplastic carcinoma of breast - an unusual histological variant.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {9}, number = {2}, pages = {ED05-6}, pmid = {25859463}, issn = {2249-782X}, abstract = {Metaplastic carcinoma of breast refers to a heterogeneous group of neoplasms characterized by intimate admixture of adenocarcinoma with dominant areas of spindle cell, squamous cell and/ or mesenchymal differentiation. They constitute the rarest histological variant of invasive ductal carcinoma. These carcinomas have aggressive clinical behaviour and show suboptimal response to standard treatment. A 49-year-old female presented with lump in the left breast for one year. She was diagnosed as infiltrating ductal carcinoma breast with triple negative hormone status by trucut biopsy. She completed four cycles of neoadjuvant chemotherapy. Postchemotherapy, axillary nodes decreased in size but the size of the primary tumour remained the same. Hence, she underwent modified radical mastectomy and the specimen sent for histopathological examination. Grossly, there was a solitary cyst measuring 4x3cm. Histologically, cyst enclosing malignant cells which resemble mature squamous epithelial cells. Also, seen are malignant cells in glandular pattern.}, } @article {pmid25852060, year = {2015}, author = {Borges, S and Perez, EA and Thompson, EA and Radisky, DC and Geiger, XJ and Storz, P}, title = {Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.}, journal = {Molecular cancer therapeutics}, volume = {14}, number = {6}, pages = {1306-1316}, pmid = {25852060}, issn = {1538-8514}, support = {CA116201/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/metabolism/prevention & control/secondary ; Lymphatic Metastasis ; MCF-7 Cells ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Confocal ; Neoplasm Invasiveness ; Protein Kinase C/*antagonists & inhibitors/genetics/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Pyrimidines/*pharmacology ; RNA Interference ; Receptors, Estrogen/metabolism ; Tumor Burden/drug effects/genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple-negative phenotype.}, } @article {pmid25850931, year = {2015}, author = {Sutton, EJ and Oh, JH and Dashevsky, BZ and Veeraraghavan, H and Apte, AP and Thakur, SB and Deasy, JO and Morris, EA}, title = {Breast cancer subtype intertumor heterogeneity: MRI-based features predict results of a genomic assay.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {42}, number = {5}, pages = {1398-1406}, pmid = {25850931}, issn = {1522-2586}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cohort Studies ; Contrast Media ; Female ; Gadolinium DTPA ; Gene Expression/genetics ; Genomics/*methods ; Humans ; Image Enhancement ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate the association between a validated, gene-expression-based, aggressiveness assay, Oncotype Dx RS, and morphological and texture-based image features extracted from magnetic resonance imaging (MRI).

MATERIALS AND METHODS: This retrospective study received Internal Review Board approval and need for informed consent was waived. Between 2006-2012, we identified breast cancer patients with: 1) ER+, PR+, and HER2- invasive ductal carcinoma (IDC); 2) preoperative breast MRI; and 3) Oncotype Dx RS test results. Extracted features included morphological, histogram, and gray-scale correlation matrix (GLCM)-based texture features computed from tumors contoured on pre- and three postcontrast MR images. Linear regression analysis was performed to investigate the association between Oncotype Dx RS and different clinical, pathologic, and imaging features. P < 0.05 was considered statistically significant.

RESULTS: Ninety-five patients with IDC were included with a median Oncotype Dx RS of 16 (range: 0-45). Using stepwise multiple linear regression modeling, two MR-derived image features, kurtosis in the first and third postcontrast images and histologic nuclear grade, were found to be significantly correlated with the Oncotype Dx RS with P = 0.0056, 0.0005, and 0.0105, respectively. The overall model resulted in statistically significant correlation with Oncotype Dx RS with an R-squared value of 0.23 (adjusted R-squared = 0.20; P = 0.0002) and a Spearman's rank correlation coefficient of 0.49 (P < 0.0001).

CONCLUSION: A model for IDC using imaging and pathology information correlates with Oncotype Dx RS scores, suggesting that image-based features could also predict the likelihood of recurrence and magnitude of chemotherapy benefit.}, } @article {pmid25848941, year = {2015}, author = {Dossus, L and Benusiglio, PR}, title = {Lobular breast cancer: incidence and genetic and non-genetic risk factors.}, journal = {Breast cancer research : BCR}, volume = {17}, number = {}, pages = {37}, pmid = {25848941}, issn = {1465-542X}, mesh = {Breast Neoplasms/*epidemiology/*etiology ; Carcinoma, Lobular/*epidemiology/*etiology ; Environment ; Female ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Humans ; Incidence ; Risk Factors ; }, abstract = {While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.}, } @article {pmid25845386, year = {2015}, author = {Lin, CS and Chang, SC and Ou, LH and Chen, CM and Hsieh, SS and Chung, YP and King, KL and Lin, SL and Wei, YH}, title = {Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {33}, number = {6}, pages = {2924-2934}, doi = {10.3892/or.2015.3887}, pmid = {25845386}, issn = {1791-2431}, mesh = {Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Cell Proliferation ; DNA Copy Number Variations/genetics ; DNA, Mitochondrial/*genetics ; Estrogen Receptor alpha/*biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/*biosynthesis/genetics ; Middle Aged ; Mutation ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; Receptors, Progesterone/*biosynthesis/genetics ; Tumor Suppressor Protein p53/*biosynthesis/genetics ; }, abstract = {We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.}, } @article {pmid25837163, year = {2015}, author = {Cha, YJ and Jung, WH and Cho, NH and Koo, JS}, title = {Expression of sarcosine metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.}, journal = {Yonsei medical journal}, volume = {56}, number = {3}, pages = {598-607}, pmid = {25837163}, issn = {1976-2437}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Phenotype ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Sarcosine/genetics/*metabolism ; Tissue Array Analysis ; }, abstract = {PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results.

MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)].

RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC.

CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.}, } @article {pmid25834613, year = {2015}, author = {Jung, NY and Kim, SH and Kim, SH and Seo, YY and Oh, JK and Choi, HS and You, WJ}, title = {Effectiveness of Breast MRI and (18)F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma.}, journal = {Journal of breast cancer}, volume = {18}, number = {1}, pages = {63-72}, pmid = {25834613}, issn = {1738-6756}, abstract = {PURPOSE: We evaluated the utility of magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC).

METHODS: The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and (18)F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups.

RESULTS: Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on (18)F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of (18)F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of (18)F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with (18)F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or (18)F-FDG PET/CT for ILC versus IDC.

CONCLUSION: The MRI and (18)F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although (18)F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of ILC as well as IDC.}, } @article {pmid25834609, year = {2015}, author = {Xue, C and Peng, RJ and Wang, SS and Shi, YX and An, X and Xu, F and Yuan, ZY}, title = {Operable breast cancer of the inner hemisphere is associated with poor survival.}, journal = {Journal of breast cancer}, volume = {18}, number = {1}, pages = {36-43}, pmid = {25834609}, issn = {1738-6756}, abstract = {PURPOSE: This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes.

METHODS: Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location.

RESULTS: The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed.

CONCLUSION: This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors.}, } @article {pmid25834604, year = {2015}, author = {Kim, H and Jang, SM and Ahn, H and Sim, J and Yi, K and Chung, Y and Han, H and Rehman, A and Chung, MS and Jang, K and Paik, SS}, title = {Clinicopathological significance of dual-specificity protein phosphatase 4 expression in invasive ductal carcinoma of the breast.}, journal = {Journal of breast cancer}, volume = {18}, number = {1}, pages = {1-7}, pmid = {25834604}, issn = {1738-6756}, abstract = {PURPOSE: Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP) 2 is a member of the inducible nuclear MKP group. The role of DUSP4 in cancer development and progression appears to vary with the type of malignancy. The purpose of this study was to investigate DUSP4 expression in a case series of invasive ductal carcinoma of the breast.

METHODS: We constructed tissue microarrays consisting of 16, 14, 47, and 266 cases of normal breast tissue, usual ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, respectively. DUSP4 expression was investigated by immunohistochemistry.

RESULTS: Cytoplasmic DUSP4 expression was observed. DUSP4 was more frequently expressed in malignant than in benign cases (p=0.024). The mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (p=0.019). DUSP4 expression was significantly correlated with a larger tumor size (>2 cm, p=0.015). There was no significant correlation between overall survival or disease-free survival and DUSP4 expression in all 266 patients. We evaluated the impact of DUSP4 expression on the survival of 120 patients with T1-stage tumors. Interestingly, Kaplan-Meier survival curves revealed that DUSP4 expression had a significant effect on both overall patient survival (p=0.034, log-rank test) and disease-free survival (p=0.045, log-rank test). In early T-stage breast cancer, DUSP4 expression was associated with a worse prognosis.

CONCLUSION: DUSP4 is frequently upregulated in breast malignancy, and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especially in patients with early T1-stage cancer.}, } @article {pmid25833969, year = {2015}, author = {Fuller, NR and Caterson, ID and Sainsbury, A and Denyer, G and Fong, M and Gerofi, J and Baqleh, K and Williams, KH and Lau, NS and Markovic, TP}, title = {The effect of a high-egg diet on cardiovascular risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) study-a 3-mo randomized controlled trial.}, journal = {The American journal of clinical nutrition}, volume = {101}, number = {4}, pages = {705-713}, doi = {10.3945/ajcn.114.096925}, pmid = {25833969}, issn = {1938-3207}, mesh = {Aged ; Blood Glucose/metabolism ; Body Mass Index ; Cardiovascular Diseases/*diet therapy/*prevention & control ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Diabetes Mellitus, Type 2/*diet therapy ; *Diet ; *Eggs ; Fatty Acids, Monounsaturated/administration & dosage/blood ; Fatty Acids, Unsaturated/administration & dosage/blood ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Nutritional Status ; Obesity/blood/diet therapy ; Overweight/blood/diet therapy ; Prospective Studies ; Risk Factors ; Satiation ; Surveys and Questionnaires ; Treatment Outcome ; Triglycerides/blood ; }, abstract = {BACKGROUND: Previously published research that examined the effects of high egg consumption in people with type 2 diabetes (T2D) produced conflicting results leading to recommendations to limit egg intake. However, people with T2D may benefit from egg consumption because eggs are a nutritious and convenient way of improving protein and micronutrient contents of the diet, which have importance for satiety and weight management.

OBJECTIVE: In this randomized controlled study, we aimed to determine whether a high-egg diet (2 eggs/d for 6 d/wk) compared with a low-egg diet (<2 eggs/wk) affected circulating lipid profiles, in particular high-density lipoprotein (HDL) cholesterol, in overweight or obese people with prediabetes or T2D.

DESIGN: A total of 140 participants were randomly assigned to one of the 2 diets as part of a 3-mo weight maintenance study. Participants attended the clinic monthly and were instructed on the specific types of foods and quantities to be consumed.

RESULTS: There was no significant difference in the change in HDL cholesterol from screening to 3 mo between groups; the mean difference (95% CI) between high- and low-egg groups was +0.02 mmol/L (-0.03, 0.08 mmol/L; P = 0.38). No between-group differences were shown for total cholesterol, low-density lipoprotein cholesterol, triglycerides, or glycemic control. Both groups were matched for protein intake, but the high-egg group reported less hunger and greater satiety postbreakfast. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intakes significantly increased from baseline in both groups.

CONCLUSIONS: High egg consumption did not have an adverse effect on the lipid profile of people with T2D in the context of increased MUFA and PUFA consumption. This study suggests that a high-egg diet can be included safely as part of the dietary management of T2D, and it may provide greater satiety. This trial was registered at the Australia New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12612001266853.}, } @article {pmid25831047, year = {2015}, author = {Kim, SY and Jung, SH and Kim, MS and Baek, IP and Lee, SH and Kim, TM and Chung, YJ and Lee, SH}, title = {Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.}, journal = {Oncotarget}, volume = {6}, number = {10}, pages = {7597-7607}, pmid = {25831047}, issn = {1949-2553}, mesh = {Adult ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Gene Dosage/*genetics ; Genomics ; Humans ; Middle Aged ; Sequence Analysis, DNA/*methods ; }, abstract = {Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.g., TP53, PIK3CA and AKT1), copy number alterations (CNAs) and chromothripses, but had significantly fewer driver genes and co-occurrence of mutation/CNAs than synchronous DCIS-IDC. We found neither recurrent nor significantly mutated genes with synchronous DCIS-IDC compared to pure DCIS, indicating that there may not be a single determinant for pure DCIS progression to IDC. Of note, synchronous DCIS genomes were closer to IDC than pure DCIS. Among the clinicopathologic parameters, progesterone receptor (PR)-negative status was associated with increased mutations, CNAs, co-occurrence of mutations/CNAs and driver mutations. Our results indicate that although pure DCIS has already acquired some drivers, more changes are needed to progress to IDC. In addition, IDC-associated DCIS is more aggressive than pure DCIS at genomic level and should really be considered IDC. Finally, the data suggest that PR-negativity could be used to predict aggressive breast cancer genotypes.}, } @article {pmid25824769, year = {2015}, author = {Ameli, F and Rose, IM and Masir, N}, title = {Expression of DDR1 and DVL1 in invasive ductal and lobular breast carcinoma does not correlate with histological type, grade and hormone receptor status.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {6}, pages = {2385-2390}, doi = {10.7314/apjcp.2015.16.6.2385}, pmid = {25824769}, issn = {2476-762X}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Cross-Sectional Studies ; Discoidin Domain Receptor 1 ; Dishevelled Proteins ; Drosophila Proteins ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Phosphoproteins/*metabolism ; Prognosis ; Receptor Protein-Tyrosine Kinases/*metabolism ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {BACKGROUND: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC.

OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.

MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.

RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.

CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.}, } @article {pmid25820821, year = {2015}, author = {Asiaf, A and Ahmad, ST and Malik, AA and Aziz, SA and Rasool, Z and Masood, A and Zargar, MA}, title = {Protein expression and methylation of MGMT, a DNA repair gene and their correlation with clinicopathological parameters in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {8}, pages = {6485-6496}, pmid = {25820821}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Methylation/*genetics ; DNA Modification Methylases/biosynthesis/*genetics ; DNA Repair Enzymes/biosynthesis/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Promoter Regions, Genetic ; Tumor Suppressor Proteins/biosynthesis/*genetics ; }, abstract = {Epigenetic mechanisms such as DNA methylation are being increasingly recognized to play an important role in cancer and may serve as a cancer biomarker. The aim of this study was to evaluate the promoter methylation status of MGMT (O6-methylguanine-DNA methyltransferase) and a possible correlation with the expression of MGMT and standard clinicopathological parameters in invasive ductal breast carcinoma patients (IDC) of Kashmir. Methylation-specific PCR was carried out to investigate the promoter methylation status of MGMT in breast tumors paired with the corresponding normal tissue samples from 128 breast cancer patients. The effect of promoter methylation on protein expression in the primary breast cancer and adjacent normal tissues was evaluated by immunohistochemistry (n = 128) and western blotting (n = 30). The frequency of tumor hypermethylation was 39.8 % and a significant difference in methylation frequency among breast tumors were found (p < 0.001) when compared with the corresponding normal tissue. Immunohistochemical analysis showed no detectable expression of MGMT in 68/128 (53.1 %) tumors. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (rs = -0.285, p = 0.001, OR = 3.38, 95 % CI = 1.59-7.17). A significant correlation was seen between loss of MGMT and lymph node involvement (p = 0.030), tumor grade (p < 0.0001), loss of estrogen receptors (ER; p = 0.021) and progesterone receptors (PR) (p = 0.016). Also, MGMT methylation was found to be associated with tumor grade (p = 0.011), tumor stage (p = 0.009), and loss of ER (p = 0.003) and PR receptors (p = 0.009). To our knowledge, our findings, for the first time, in Kashmiri population, indicate that MGMT is aberrantly methylated in breast cancer and promoter hypermethylation could be attributed to silencing of MGMT gene expression in breast cancer. Our data suggests that MGMT promoter hypermethylation could have a potential function as molecular biomarker of breast oncogenesis. Also, based on their predictive value of response to therapy, the immunohistochemical evaluation and interpretation of MGMT may also help in future to establish therapeutic strategies for patients with breast cancer.}, } @article {pmid25819175, year = {2015}, author = {Komatsu, S and Ichikawa, D and Miyamae, M and Kawaguchi, T and Morimura, R and Hirajima, S and Okajima, W and Ohashi, T and Imamura, T and Konishi, H and Shiozaki, A and Ikoma, H and Okamoto, K and Taniguchi, H and Otsuji, E}, title = {Malignant potential in pancreatic neoplasm; new insights provided by circulating miR-223 in plasma.}, journal = {Expert opinion on biological therapy}, volume = {15}, number = {6}, pages = {773-785}, doi = {10.1517/14712598.2015.1029914}, pmid = {25819175}, issn = {1744-7682}, mesh = {Adenocarcinoma, Mucinous/blood/diagnosis ; Aged ; Biomarkers, Tumor/blood ; Carcinoma, Pancreatic Ductal/*blood/*diagnosis ; Cohort Studies ; Female ; Humans ; Male ; MicroRNAs/*blood ; Middle Aged ; Neoplasm Invasiveness/pathology ; Pancreas/metabolism/pathology ; Pancreatic Neoplasms/*blood/*diagnosis ; }, abstract = {BACKGROUND: Recent studies have identified that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory vesicles.

METHODS: We tested miR-223 as a candidate of novel plasma biomarker in pancreatic cancer (PCa) and intraductal papillary mucinous neoplasm (IPMN).

RESULTS: i) miR-223 expression was significantly higher in PCa tissues (p = 0.0069) than in normal tissues. ii) Plasma miR-223 levels were significantly higher in 71 PCa patients than 67 healthy volunteers (p < 0.0001). iii) Plasma miR-223 levels were significantly reduced in postoperative samples (p = 0.0297). iv) Plasma miR-223 levels tended to discriminate the malignant potential between benign IPMN and malignant IPMN (p = 0.0963), and the progressive extent of invasiveness between malignant IPMN and pancreatic invasive ductal carcinoma (PIDC) (p = 0.0004). Multivariate logistic regression analysis revealed that a low level of plasma miR-223 was an independent risk factor for PIDC (p = 0.0012, odds ratio 7.90 [95% CI: 2.06 - 41.2]). v) There was no significant correlation between plasma miR-223 levels and the number of any blood cell types in the peripheral blood.

CONCLUSION: Plasma miR-223 might be a clinically useful biomarker for screening PCa, and predicting malignant potential of IPMN and the invasiveness of PCa.}, } @article {pmid25818398, year = {2015}, author = {Jafarian, N and Kuppler, K and Rosa, M and Hoover, S and Patel, B}, title = {Chronic Lymphocytic Leukemia and Invasive Ductal Carcinoma Presenting as a Collision Breast Tumor.}, journal = {Clinical breast cancer}, volume = {15}, number = {4}, pages = {e209-12}, doi = {10.1016/j.clbc.2015.02.001}, pmid = {25818398}, issn = {1938-0666}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Neoplasms, Second Primary/*pathology ; }, } @article {pmid25818033, year = {2015}, author = {Oger, AS and Boukerrou, M and Cutuli, B and Campion, L and Rousseau, E and Bussières, E and Raro, P and Classe, JM}, title = {[Male breast cancer: prognostic factors, diagnosis and treatment: a multi-institutional survey of 95 cases].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {43}, number = {4}, pages = {290-296}, doi = {10.1016/j.gyobfe.2015.02.010}, pmid = {25818033}, issn = {1769-6682}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*diagnosis/pathology/*therapy ; Carcinoma, Ductal, Breast/diagnosis/pathology/therapy ; Chemotherapy, Adjuvant ; Humans ; Lymphatic Metastasis/pathology ; Male ; Mastectomy ; Middle Aged ; Obesity/complications ; Prognosis ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVES: The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer.

METHODS: This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergonié Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis.

RESULTS: The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific.

CONCLUSION: Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.}, } @article {pmid25817822, year = {2015}, author = {Shao, F and Guo, T and Chua, PJ and Tang, L and Thike, AA and Tan, PH and Bay, BH and Baeg, GH}, title = {Clinicopathological significance of ARID1B in breast invasive ductal carcinoma.}, journal = {Histopathology}, volume = {67}, number = {5}, pages = {709-718}, doi = {10.1111/his.12701}, pmid = {25817822}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; DNA-Binding Proteins/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Tissue Array Analysis ; Transcription Factors/analysis/*biosynthesis ; Transfection ; }, abstract = {AIMS: Identification of prognostic and predictive biomarkers for breast cancer is essential to better stratify patients for treatment and evaluate patient outcome. AT-rich interactive domain-containing protein 1B (ARID1B) is implicated in cell proliferation, but its role in tumorigenesis remains unclear.

METHODS AND RESULTS: Immunohistochemical analysis of ARID1B expression using breast cancer tissue microarrays containing 156 breast invasive ductal carcinoma patient samples and subsequent statistical data analysis based on ARID1B immunoreactivity score were performed to examine the correlation between clinicopathological parameters in breast cancer and ARID1B expression. In-vitro assays were also performed to study the role of ARID1B in cell cycle progression. Univariate analysis revealed that high ARID1B expression is correlated closely with histological grade (P = 0.045) and size (P = 0.043) of invasive breast cancer. These findings were confirmed by multivariate analysis. Notably, increased ARID1B expression was frequently detected in the aggressive triple-negative breast cancer subtypes (P = 0.039) and associated with decreased 5-year disease-free survival rate. Lastly, MDA-MB-231 cells with reduced ARID1B activity displayed a delay in G1 to S phase cell cycle transition and consequently showed a decrease in cell proliferation compared with controls (P < 0.001).

CONCLUSIONS: ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer.}, } @article {pmid25816287, year = {2015}, author = {Rebollo, MP and Mohammed, KA and Thomas, B and Ame, S and Ali, SM and Cano, J and Escalada, AG and Bockarie, MJ}, title = {Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?.}, journal = {PLoS neglected tropical diseases}, volume = {9}, number = {3}, pages = {e0003669}, pmid = {25816287}, issn = {1935-2735}, support = {G1001337/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Communicable Disease Control/*methods ; Disease Eradication/methods/*statistics & numerical data ; Elephantiasis, Filarial/*drug therapy/*epidemiology/*transmission ; Humans ; Indian Ocean Islands/epidemiology ; Male ; Surveys and Questionnaires ; Tanzania/epidemiology ; }, abstract = {BACKGROUND: Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.

In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded.

CONCLUSIONS: Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.}, } @article {pmid25809301, year = {2015}, author = {Calandrella, D and Romito, LM and Elia, AE and Del Sorbo, F and Bagella, CF and Falsitta, M and Albanese, A}, title = {Causes of withdrawal of duodenal levodopa infusion in advanced Parkinson disease.}, journal = {Neurology}, volume = {84}, number = {16}, pages = {1669-1672}, doi = {10.1212/WNL.0000000000001500}, pmid = {25809301}, issn = {1526-632X}, mesh = {Aged ; Antiparkinson Agents/administration & dosage/*adverse effects ; Duodenum/surgery ; Female ; Humans ; Infusion Pumps, Implantable/*adverse effects ; Infusions, Parenteral/*adverse effects ; Levodopa/administration & dosage/*adverse effects ; Male ; Middle Aged ; Parkinson Disease/*drug therapy ; }, abstract = {OBJECTIVE: We performed a real-life observation of patients with Parkinson disease (PD) who received duodenal levodopa infusion (DLI) to determine which adverse events caused treatment discontinuation and when such events occurred.

METHODS: All consecutive patients with PD treated at the Carlo Besta Neurological Institute were included. The patients were evaluated at baseline and after DLI at regular intervals. Their motor condition was assessed and adverse events were recorded.

RESULTS: Thirty-five patients with PD (15 men and 20 women) were included. They received DLI implants between October 2007 and September 2013. Four patients died of causes unrelated to the procedure. At the end of the study, 21 patients (60%) were still on treatment. DLI provided efficacious motor control in all patients. Discontinuation was most frequently caused by device- or infusion-related adverse events. Ten patients of the remaining 31 discontinued DLI. There were 2 main causes of withdrawal: stoma infection (4 patients), and worsening of dyskinesias not manageable with infusion reduction (3 patients). In most patients, discontinuations occurred during the first year after implant. Risk of discontinuation was related to age at implant, but no other demographic or clinical variables.

CONCLUSIONS: We identified 2 main causes leading to DLI withdrawal during the first year postimplant and suggest adopting measures to prevent such occurrences. Elderly patients are at higher risk of treatment discontinuation.}, } @article {pmid25808597, year = {2016}, author = {Morimoto, M and Bando, Y and Nakagawa, M and Takechi, H and Yoshida, T and Honda, J and Tadokoro, Y and Moriya, T and Sasa, M and Tangoku, A}, title = {Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {4}, pages = {577-582}, doi = {10.1007/s12282-015-0605-z}, pmid = {25808597}, issn = {1880-4233}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Female ; Humans ; Immunohistochemistry/*methods ; Ki-67 Antigen/*analysis/metabolism ; Middle Aged ; Receptor, ErbB-2/*analysis/metabolism ; Reproducibility of Results ; }, abstract = {BACKGROUND: Re-evaluation of the subtype of recurrent breast cancer is necessary for deciding the treatment approach, but it is often not performed due to the difficulty of obtaining tissue specimens from a recurrent lesion, etc. However, when a recurrent lesion is close to the body surface, fine-needle aspiration cells (FNA cells) can be easily obtained, and immunocytochemical (ICC) analysis of hormone receptors expression in FNA cells is said to be highly reliable. However, there is no consensus regarding ICC analysis of human epidermal growth factor receptor type 2 (HER2) expression and the Ki67 index using FNA cells.

METHODS: Touch-smear cells (TSC) were prepared from resected specimens from 36 patients with primary invasive ductal carcinoma of the breast. The TSC were fixed in 95 % ethanol and subjected to ICC analysis for HER2 using HercepTest™ (Dako) and Ki67 using MIB-1™ (Dako). HER2 expression and the Ki67 index for the TSC were compared with the results of immunohistochemical analysis of histological section (HS). Statistical analyses used the kappa test and Pearson's correlation coefficients.

RESULTS: HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001).

CONCLUSIONS: The reliability of ICC analysis of HER2 expression and the Ki67 index using TSC were recognized.}, } @article {pmid25808049, year = {2017}, author = {Fennig, S and Brunstein Klomek, A and Shahar, B and Sarel-Michnik, Z and Hadas, A}, title = {Inpatient treatment has no impact on the core thoughts and perceptions in adolescents with anorexia nervosa.}, journal = {Early intervention in psychiatry}, volume = {11}, number = {3}, pages = {200-207}, doi = {10.1111/eip.12234}, pmid = {25808049}, issn = {1751-7893}, mesh = {Adolescent ; Adolescent Behavior ; Anorexia Nervosa/*psychology/therapy ; Child ; Combined Modality Therapy ; Female ; Humans ; Inpatients ; Male ; *Perception ; *Thinking ; Treatment Outcome ; }, abstract = {AIM: Examine changes in core perceptions and thoughts during the weight restoration phase of inpatient treatment for adolescents with anorexia nervosa.

METHOD: Forty-four adolescents with anorexia nervosa consecutively admitted (2009-2012) to an inpatient paediatric-psychiatric unit specializing in eating disorders. The programme consisted of a complete inpatient intervention combining weight restoration by structured supervised meals with individual and group cognitive-behavioural therapy, parental training/family intervention and educational activities, followed by a half-way day-treatment weight-stabilizing phase and progressive reintroduction to the community. The study focused on changes from hospital admission to discharge in patients' responses to self-report questionnaires on eating disorder symptoms, depression, anxiety and suicidal ideation.

RESULTS: No significant changes in core anorexic thoughts and perceptions as Body dissatisfaction, Drive for thinness, Weight concern and Shape concern were noted. However, a reduction in the general severity of eating disorder symptoms (including Restraint and Eating concern) was observed, mainly related to the treatment structure. Levels of depression significantly decreased but remained within pathological range. We also found a concerning increase in suicidal ideation not correlated with a concomitant increase in depressive symptomatology.

CONCLUSIONS: Inpatient treatment of anorexia nervosa in adolescents does not significantly modify core anorexic thoughts and perceptions. This may explain the high relapse rates. Changes in core beliefs may be crucial for recovery and prevention of relapse in anorexia nervosa at this critical age. This study may have clinical implications for the development of better treatment strategies to target the gap between disturbed thoughts and distorted perceptions - the core aspects of anorexia nervosa and physical recovery during and after the weight restoration phase.}, } @article {pmid25804795, year = {2015}, author = {Wang, T and Ma, Y and Wang, L and Liu, H and Chen, M and Niu, R}, title = {Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {8}, pages = {6113-6124}, pmid = {25804795}, issn = {1423-0380}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*biosynthesis/genetics ; }, abstract = {The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.}, } @article {pmid25802254, year = {2015}, author = {Abdalla, S and Macneal, P and Borg, CM}, title = {Metastases of lobular breast carcinoma in the terminal ileum and ileocaecal valve.}, journal = {Journal of surgical case reports}, volume = {2015}, number = {3}, pages = {}, pmid = {25802254}, issn = {2042-8812}, abstract = {Gastrointestinal (GI) metastases from primary breast carcinoma are rare but more common in invasive lobular carcinoma than invasive ductal carcinoma. The symptoms may be non-specific and the presentation can occur many years after the initial primary breast carcinoma. Radiological and endoscopic findings can be difficult to distinguish from inflammatory bowel disease and primary carcinoma of the GI tract. Histological and immunohistopathology assessment will usually confirm the diagnosis of metastatic breast carcinoma. We report the first case of lobular breast carcinoma metastasizing to the terminal ileum and ileocaecal valve 19 years following treatment for breast cancer in an 82-year-old woman. Staging investigations revealed synchronous metastases in bones and the pleura. A high index of suspicion and awareness of the potential long interval in the presentation of metastatic breast cancer help in making an accurate diagnosis and rapid clinical management.}, } @article {pmid25798882, year = {2015}, author = {Budrukkar, A and Gurram, L and Upreti, RR and Munshi, A and Jalali, R and Badwe, R and Parmar, V and Shet, T and Gupta, S and Wadasadawala, T and Sarin, R}, title = {Clinical outcomes of prospectively treated 140 women with early stage breast cancer using accelerated partial breast irradiation with 3 dimensional computerized tomography based brachytherapy.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {115}, number = {3}, pages = {349-354}, doi = {10.1016/j.radonc.2015.03.002}, pmid = {25798882}, issn = {1879-0887}, mesh = {Adult ; Aged ; Brachytherapy/*methods ; Breast Neoplasms/diagnostic imaging/pathology/*radiotherapy ; Carcinoma, Ductal/diagnostic imaging/radiotherapy ; Female ; Humans ; Imaging, Three-Dimensional ; Middle Aged ; Neoplasm Staging ; Radiotherapy Dosage ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {PURPOSE: To study the clinical outcomes of women with early breast cancer (EBC) treated with accelerated partial breast irradiation (APBI) with multicatheter interstitial brachytherapy (MIB) using 3 dimensional computerized tomography (3DCT) based planning.

MATERIALS AND METHODS: During August 2005 to January 2013, 140 women with EBC were treated prospectively with APBI using high dose rate (HDR) MIB. After 3DCT based planning patients were treated to a dose of 34 Gy/10 #/1 week with bid regimen.

RESULTS: Median age was 57 years and tumor size 2 cm (range: 0.6-3.2 cm). Infiltrating duct carcinoma (IDC) was the most common histology; grade III tumors were seen in 82%. Median dose homogeneity index (DHI) was 0.76 (range: 0.49-0.85). The median coverage index (CI) of the cavity was 90% (61.4-100) and 80.5% (53.6-97.4) for planning target volume (PTV). Median follow up was 60 months (1-102 months). The 5 and 7 year local control rates (LC) were 97% and 92% respectively. Her2 positivity was the only prognostic factor which had an adverse impact on LC (p=0.01). Five and 7 year disease free survival (DFS) and overall survival (OAS) were 93%, 84%, 97.5% and 89% respectively. Good to excellent cosmetic outcomes at last follow up were seen in 87 (77%) women.

CONCLUSIONS: 3DCT based MIB results in excellent long term outcomes and good to excellent cosmesis. Her2 positivity has an adverse impact on LC rates.}, } @article {pmid25791599, year = {2015}, author = {Karbiener, M and Scheideler, M}, title = {Microarray analysis of small non-coding RNAs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1296}, number = {}, pages = {161-171}, doi = {10.1007/978-1-4939-2547-6_15}, pmid = {25791599}, issn = {1940-6029}, mesh = {Microarray Analysis/*methods ; Nucleic Acid Hybridization/methods ; Oligonucleotide Probes/genetics ; RNA, Small Untranslated/*genetics ; Transition Temperature ; }, abstract = {Microarray technology has evolved to efficiently profile the expression of RNAs. However, analysis of small non-coding RNAs (ncRNAs) is challenging due to their short length and highly divergent sequences with large variation in GC content leading to very different hybridization properties. To overcome these challenges, LNA-modified oligonucleotides have been used to enhance and normalize the melting temperature (Tm) of capture probes, which allows sensitive profiling of small ncRNAs regardless of their sequence. Here, we describe the isolation and labeling of small non-coding RNAs, as well as their hybridization to microarrays with LNA-modified oligonucleotide probes using a semi-automated hybridization device.}, } @article {pmid25785083, year = {2015}, author = {Tian, P and Zhang, W and Zhao, H and Lei, Y and Cui, L and Wang, W and Li, Q and Zhu, Q and Zhang, Y and Xu, Z}, title = {Intraoperative diagnosis of benign and malignant breast tissues by fourier transform infrared spectroscopy and support vector machine classification.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {1}, pages = {972-981}, pmid = {25785083}, issn = {1940-5901}, abstract = {BACKGROUND: Fourier transform infrared (FTIR) spectroscopy has shown its unique advantages in distinguishing cancerous tissue from normal one. The aim of this study was to establish a quick and accurate diagnostic method of FTIR spectroscopy to differentiate malignancies from benign breast tissues intraoperatively.

MATERIALS AND METHODS: In this study, a total of 100 breast tissue samples obtained from 100 patients were taken on surgery. All tissue samples were scanned for spectra intraoperatively before being processed for histopathological diagnosis. Standard normal variate (SNV) method was adopted to reduce scatter effects. Support vector machine (SVM) classification was used to discriminate spectra between malignant and benign breast tissues. Leave-one-out cross validation (LOOCV) was used to evaluate the discrimination.

RESULTS: According to histopathological examination, 50 cases were diagnosed as fibroadenoma and 50 cases as invasive ductal carcinoma. The results of SVM algorithm showed that the sensitivity, specificity and accuracy rate of this method are 90.0%, 98.0% and 94.0%, respectively.

CONCLUSIONS: FTIR spectroscopy technique in combination with SVM classification could be an accurate, rapid and objective tool to differentiate malignant from benign tumors during operation. Our studies establish the feasibility of FTIR spectroscopy with chemometrics method to guide surgeons during the surgery as an effective supplement for pathological diagnosis on frozen section.}, } @article {pmid25785005, year = {2015}, author = {Feng, M and Feng, C and Yu, Z and Fu, Q and Ma, Z and Wang, F and Wang, F and Yu, L}, title = {Histopathological alterations during breast carcinogenesis in a rat model induced by 7,12-Dimethylbenz (a) anthracene and estrogen-progestogen combinations.}, journal = {International journal of clinical and experimental medicine}, volume = {8}, number = {1}, pages = {346-357}, pmid = {25785005}, issn = {1940-5901}, abstract = {Studies have shown that the development of breast cancer (BC) is a multi-step process that occurs sequentially from normal to usual hyperplasia, atypical hyperplasia, carcinoma in situ, and finally the invasive stages of carcinoma. Our study investigated the histopathological alterations in breast tissue in a Sprague-Dawley (SD) rat model induced by 7,12-Dimethylbenz (a) anthracene (DMBA) and estrogen-progestogen (E-P). Fifty rats were randomly divided into five groups (n = 10 each) and administered the E-P/DMBA combination. After the induction of BC, breast tissue samples were obtained from the rats and stained with hematoxylin-eosin (HE). Breast tissues from 10 rats and 10 human patients were obtained for comparison. The expression of P63, CK5/6 and CK34βE12 was observed and analyzed using the SPSS 17.0 software. The HE results showed ductal epithelial hyperplasia with forming a second lumen or papillary structure, atypical hyperplasia with atypical proliferative cells, forming a cross-bridge or cribriform structure in breast tissues from the rats samples. The IHC results showed that the expression of P63 was not significantly different between rat and human breast tissue (P > 0.05), but its expression in rat and human tissue was significantly different between UDH, ADH, DCIS and IDC (P < 0.01). A similar trend was observed for the expression of CK5/6 and CK34βE12 too. Thus, the findings in this model may reflect the histopathological changes that occur during the progression of human BC. Therefore, this model could be used for the establishment of BC models to investigate the prevention and treatment of BC.}, } @article {pmid25784697, year = {2015}, author = {Leonhardt, I and Spielberg, S and Weber, M and Albrecht-Eckardt, D and Bläss, M and Claus, R and Barz, D and Scherlach, K and Hertweck, C and Löffler, J and Hünniger, K and Kurzai, O}, title = {The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.}, journal = {mBio}, volume = {6}, number = {2}, pages = {e00143}, pmid = {25784697}, issn = {2150-7511}, mesh = {Adaptive Immunity/*drug effects ; Candida albicans/*physiology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/drug effects/immunology ; Farnesol/*metabolism ; Gene Expression Profiling ; Humans ; Immunologic Factors/*metabolism ; Monocytes/drug effects/immunology ; Neutrophils/drug effects/immunology ; *Quorum Sensing ; Virulence Factors/*metabolism ; }, abstract = {UNLABELLED: Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.

IMPORTANCE: Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be important for fungal clearance and protective immunity. We show that farnesol is able to enhance inflammation by inducing activation of neutrophils and monocytes. At the same time, farnesol impairs differentiation of monocytes into immature dendritic cells (iDC) by modulating surface phenotype, cytokine release and migrational behavior. Consequently, iDC generated in the presence of farnesol are unable to induce proper T cell responses and fail to secrete Th1 promoting interleukin 12 (IL-12). As farnesol induced down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, desensitization to GM-CSF could potentially explain transcriptional reprofiling of iDC effector molecules. Taken together, our data show that farnesol can also mediate Candida-host communication and is able to act as a virulence factor.}, } @article {pmid25783336, year = {2015}, author = {Kushnir, J and Djerassi, R and Sofer, T and Kushnir, T}, title = {Threat perception, anxiety and noncompliance with preoperative fasting instructions among mothers of children attending elective same day surgery.}, journal = {Journal of pediatric surgery}, volume = {50}, number = {5}, pages = {869-874}, doi = {10.1016/j.jpedsurg.2014.08.018}, pmid = {25783336}, issn = {1531-5037}, mesh = {Adult ; *Ambulatory Surgical Procedures ; Anxiety/*epidemiology/etiology ; Child ; Child, Preschool ; *Elective Surgical Procedures ; *Fasting ; Female ; Humans ; Incidence ; Israel/epidemiology ; Male ; Mothers/*psychology ; *Patient Compliance ; Preoperative Care/*methods ; }, abstract = {PURPOSE: The current study examined possible links between threat perception, anxiety, conscientiousness and parental noncompliance with preoperative fasting instructions for their children.

METHODS: 100 mothers of children about to undergo an ambulatory elective surgery were divided to two equal groups based on compliance/noncompliance with pre surgery fasting requirements. Logistic regression analysis was preformed to predict compliance/noncompliance. In addition a logistic model estimating the effect of anxiety and conscientiousness levels, and their interaction, on the probability of fasting was performed.

RESULTS: Mothers who did not comply with fasting requirements perceived the procedure as more threatening, were more anxious and had lower conscientiousness levels. Additionally, mother's anxiety prior to surgery mediated the association between mothers' threat perception and compliance. Finally, conscientiousness moderated the anxiety and compliance association so that high conscientiousness levels reduced the effect of anxiety, elevating the likelihood of anxious mothers to comply with fasting guidelines.

CONCLUSIONS: Based on these findings we recommend medical staff to make significant efforts to identify highly anxious parents as early as possible during the preoperative process. Innovative assessment and intervention tools should be developed in order to conduct a smooth medical operation and reduce the chance of unnecessary and costly surgery cancelation.}, } @article {pmid25776197, year = {2015}, author = {Yu, JI and Choi, DH and Huh, SJ and Cho, EY and Kim, K and Chie, EK and Ha, SW and Park, IA and Ahn, SJ and Lee, JS and Shin, KH and Kwon, Y and Kim, YB and Suh, CO and Koo, JS and Kim, JH and Jeong, BG and Kim, IA and Lee, JH and Park, W}, title = {Differences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case-Control Study (KROG 13-06).}, journal = {Clinical breast cancer}, volume = {15}, number = {5}, pages = {353-61.e1-2}, doi = {10.1016/j.clbc.2015.01.008}, pmid = {25776197}, issn = {1938-0666}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/*pathology/therapy ; Carcinoma, Papillary/*mortality/*pathology/therapy ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {PURPOSE: We designed the present study to investigate differences in prognostic factors and failure patterns between patients with invasive micropapillary carcinoma or carcinoma with micropapillary component (IMPC) and randomly matched patients with invasive ductal carcinoma (IDC) of the breast at multiple institutions of the Korean Radiation Oncology Group (KROG).

MATERIALS AND METHODS: This retrospective multicenter study was performed using subjects treated from January 1999 to November 2011. Female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy were considered for this study. Exact matches were made for age (± 3 years), pathologic tumor and node stage, treatment method (surgery with or without radiotherapy), and period when surgery was performed (within 1 year) at the same institution.

RESULTS: A total of 534 patients were analyzed. The median follow-up period was 59 months in both groups. In the comparison of clinicopathologic characteristics, rates of lymphovascular invasion (LVI) and nuclear grade III were both significantly higher in IMPC than in IDC (P < .001, P = .01, respectively). During the follow-up period, recurrences developed in 40 patients with IMPC (15.0%) and 21 with IDC (7.9%). Locoregional recurrence (LRR) developed in 22 patients with IMPC (8.2%) and 10 with IDC (3.7%). The rate of distant metastasis did not differ between the 2 groups (P = .52). LRR-free survival (P = .03) and recurrence-free survival (P = .007) were significantly different between the 2 groups, but overall survival was not (P = .67).

CONCLUSION: IMPC is associated with a higher rate of LVI, high nuclear grade, and a propensity for LRR compared to IDC. Modification of the locoregional treatment modality might be needed in this pathologic subtype of breast cancer.}, } @article {pmid25774234, year = {2015}, author = {Jo, I and Zeon, SK and Kim, SH and Kim, HW and Kang, SH and Kwon, SY and Kim, SJ}, title = {Correlation of Primary Tumor FDG Uptake with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.}, journal = {Nuclear medicine and molecular imaging}, volume = {49}, number = {1}, pages = {19-25}, pmid = {25774234}, issn = {1869-3474}, abstract = {PURPOSE: The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast.

METHODS: We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUVmax) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status.

RESULTS: The high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUVmax compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis.

CONCLUSIONS: In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer.}, } @article {pmid25773317, year = {2016}, author = {Kanat-Maymon, Y and Roth, G and Assor, A and Raizer, A}, title = {Controlled by Love: The Harmful Relational Consequences of Perceived Conditional Positive Regard.}, journal = {Journal of personality}, volume = {84}, number = {4}, pages = {446-460}, doi = {10.1111/jopy.12171}, pmid = {25773317}, issn = {1467-6494}, mesh = {Adult ; Fathers ; Female ; Friends ; Humans ; *Interpersonal Relations ; *Love ; Male ; Mothers ; *Personal Autonomy ; *Personal Satisfaction ; Sexual Partners ; Young Adult ; }, abstract = {Research on conditional positive regard (CPR) has shown that this seemingly benign practice has maladaptive correlates when used by parents. However, there is no research on the correlates of this practice in romantic relationships or on the processes mediating its effects. Building on self-determination theory (Deci & Ryan,), three studies tested the hypothesis that perceived CPR impairs relationship quality, partly because it undermines the fulfillment of the basic psychological needs for autonomy and relatedness. Study 1 (N = 125) examined perceived CPR and relationship quality across four relationship targets: mother, father, romantic partner, and best friend. Study 2, involving romantic partners (N = 142), examined whether needs fulfillment mediated the association between perceived CPR and relationship quality. Study 3, involving romantic dyads (N = 85), also included partner reports on CPR. Across the three studies, CPR was linked with poor relationship quality between relationships, between people, and between dyadic partners. Moreover, results of Study 2 and Study 3 revealed that the inverse association between perceived CPR and relationship quality was mediated by dissatisfaction of autonomy but not relatedness. Despite its seemingly benign nature, CPR is detrimental to relationship quality, partly because it thwarts the basic need for autonomy.}, } @article {pmid25771081, year = {2015}, author = {Sorin, T and Fyad, JP and Delay, E and Rouanet, P and Rimareix, F and Houpeau, JL and Classe, JM and Garrido, I and Tunon De Lara, C and Dauplat, J and Bendavid, C and Houvenaeghel, G and Clough, KB and Sarfati, I and Leymarie, N and Trudel, M and Salleron, J and Guillemin, F and Oldrini, G and Brix, M and Dolivet, G and Simon, E and Verhaeghe, JL and Marchal, F}, title = {Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {24}, number = {3}, pages = {272-277}, doi = {10.1016/j.breast.2015.02.033}, pmid = {25771081}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/secondary/surgery ; Carcinoma, Lobular/*epidemiology/secondary/surgery ; Female ; Humans ; Incidence ; Mammaplasty/*statistics & numerical data ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Unknown Primary/*epidemiology ; Retrospective Studies ; }, abstract = {Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.}, } @article {pmid25771080, year = {2015}, author = {Meshkat, B and Prichard, RS and Al-Hilli, Z and Bass, GA and Quinn, C and O'Doherty, A and Rothwell, J and Geraghty, J and Evoy, D and McDermott, EW}, title = {A comparison of clinical-pathological characteristics between symptomatic and interval breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {24}, number = {3}, pages = {278-282}, doi = {10.1016/j.breast.2015.02.032}, pmid = {25771080}, issn = {1532-3080}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/chemistry/*diagnosis/epidemiology ; Carcinoma, Ductal, Breast/chemistry/*diagnosis/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*diagnosis/epidemiology ; Early Detection of Cancer/methods/*statistics & numerical data ; Female ; Humans ; Ireland ; *Mammography ; Mass Screening ; Middle Aged ; National Health Programs ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2 ; Retrospective Studies ; Symptom Assessment ; Time Factors ; }, abstract = {BACKGROUND: An association between interval breast cancers (cancer detected after a normal mammogram and before the next scheduled mammogram) and tumour aggressiveness has been postulated which may reflect their relatively poor overall prognosis. The aim of this study was to evaluate known prognostic features of screen detected breast cancers compared to interval breast cancers.

METHODS: Patients diagnosed with breast cancer between January 2010 and 2013 at a single unit of the National Breast Screening Program (NBSP) in Ireland and those between the ages of 50 and 65 diagnosed at a symptomatic breast clinic were included in the study. Patients who had not had a screening mammogram within the proceeding two years or had a previous history of breast cancer were excluded. Data were retrospectively collected on patient demographics, tumour type, grade, hormone receptor status and stage of disease at presentation.

RESULTS: There were 915 patients included in the study, with 92% (n = 844) diagnosed through the NBSP. Ductal carcinoma in-situ accounted for 19% (n = 160) of screen-detected breast cancers but only 2.8% of interval cancers (p < 0.05). The most common type of invasive cancer was invasive ductal carcinoma. Tumour grade was significantly higher in interval breast cancers (p < 0.05). Interval cancers were identified at a significantly higher stage (Stage 1 versus 2; p < 0.001) than screen-detected cancers. Interval breast cancers were less likely to be ER positive (76% versus 81%; p < 0.05) and significantly more likely to over-express HER2 (20% vs 10%, p < 0.05) than screen-detected cancers.

CONCLUSION: This study highlights the fact that interval cancers appear to have a number of adverse prognostic markers for overall breast cancer survival when compared to women with screen-detected breast cancers. Interval cancers were more likely to be invasive, of a higher grade and stage and with a greater predominance of HER2 and triple negative molecular subtypes. Therefore this heterogeneous group of tumours may be biologically more aggressive and account disproportionately to overall breast cancer mortality.}, } @article {pmid25770021, year = {2015}, author = {Sim, YT and Vinnicombe, S and Whelehan, P and Thomson, K and Evans, A}, title = {Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer.}, journal = {Clinical radiology}, volume = {70}, number = {6}, pages = {604-609}, doi = {10.1016/j.crad.2015.02.004}, pmid = {25770021}, issn = {1365-229X}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Carcinoma, Lobular/*diagnostic imaging ; Case-Control Studies ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Mammography ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {AIM: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients.

MATERIALS AND METHODS: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests.

RESULTS: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01).

CONCLUSION: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious.}, } @article {pmid25769963, year = {2015}, author = {Cassinello, F and Prieto, I and del Olmo, M and Rivas, S and Strichartz, GR}, title = {Cancer surgery: how may anesthesia influence outcome?.}, journal = {Journal of clinical anesthesia}, volume = {27}, number = {3}, pages = {262-272}, doi = {10.1016/j.jclinane.2015.02.007}, pmid = {25769963}, issn = {1873-4529}, mesh = {Anesthesia/*methods ; Anesthetics, Local/pharmacology ; Apoptosis ; Cell Movement ; Cell Proliferation ; Disease Progression ; Humans ; Neoplasms/mortality/pathology/*surgery ; Substance P/physiology ; Voltage-Gated Sodium Channels/drug effects ; }, abstract = {OBJECTIVE: To review the published literature regarding the effects of anesthesia on cancer surgery to prevent tumor cell proliferation/migration or induce apoptosis.

BACKGROUND: Surgery is the main treatment for potentially curable solid tumors, but most cancer-related deaths in patients who have received previous surgical treatment are caused by metastatic disease. There is increasing evidence that anesthetic technique has the potential to affect long-term outcome after cancer surgery.

METHODS: This work reviews the English published literature that was obtained by performing a search of the PubMed database up to January 2014. We selected articles that provided evidence or reviewed the possible actions of anesthetics on cancer cells or the influence of anesthesia in recurrence/outcome.

RESULTS: Inhaled anesthetics induce immunosuppression and activate inflammatory cascade activation, whereas propofol has a protective action. Opioids might promote cancer recurrence and metastasis. In vitro and in vivo studies have demonstrated that local anesthetics inhibit proliferation and migration of cancer cells and induce apoptosis.

CONCLUSIONS: Anesthesiologists should follow current best clinical practice and include all strategies that effectively decrease pain and attenuate stress. Regional anesthesia and multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role in the control of perioperative pain and may improve recurrence-free survival.}, } @article {pmid25767340, year = {2014}, author = {Jana, D and Sarkar, DK and Ganguly, S and Banerjee, A and Manna, AK and Mandal, S}, title = {Can molecular subtyping replace axillary nodal status as prognostic marker in breast cancer?.}, journal = {Indian journal of surgical oncology}, volume = {5}, number = {4}, pages = {282-289}, pmid = {25767340}, issn = {0975-7651}, abstract = {Subtypes are an established prognostic factor of BC in western population but its significance in Indian BC patients has not been evaluated. Thus this study provides an insight into the prognostic significance of molecular classification and its effect on the survival of BC patients in Eastern India. In this hospital based study 242 BC patients attending a Comprehensive Breast Service Clinic of a reputed institute in Eastern India and having IDC were studied over a period of 7 years (January 2007 to October 2013). Nonluminal HER-2-positive and Triple negative tumors were associated with advanced stage of disease, metastatic lymph nodes and NPI ≥5.4, whereas Luminal 1 and Luminal 2 tumors were associated with early stage, uninvolved lymph nodes and NPI <5.4. Better survival was observed for the patients with Luminal 1 [OS = 57.1 % (n = 36)] and Luminal 2 [OS = 60.0 % (n = 6)], compared to Triple negative [OS = 33.6 % (n = 38)] and nonluminal HER-2-positive tumors [OS = 32.1 % (n = 18)]. This study provided some idea about the pattern of BC on the basis of classification by molecular profiling. Our study indicated that Triple negative and nonluminal HER-2-positive tumors have reduced DFS and OS compared with luminal 1 and 2 subtypes. In our patients, Triple negative and nonluminal HER-2-positive tumors were associated with established unfavorable prognostic indicators and this reflects the data in the western literature. The results suggest that the molecular subtypes are an independent prognostic and predictive marker in Indian BC patients. Whether or not molecular subtyping of breast cancer can replace axillary lymph nodes as the standard in prognosis remains to be seen, but if molecular subtyping can provide more information than the axilla about the prognosis and treatment option, it may well be the future of prognostication.}, } @article {pmid25759617, year = {2014}, author = {Basaran, D and Turgal, M and Beksac, K and Ozyuncu, O and Aran, O and Beksac, MS}, title = {Pregnancy-associated breast cancer: clinicopathological characteristics of 20 cases with a focus on identifiable causes of diagnostic delay.}, journal = {Breast care (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {355-359}, pmid = {25759617}, issn = {1661-3791}, abstract = {BACKGROUND: The primary objective of this study was to evaluate the clinicopathological characteristics of patients with pregnancy-associated breast cancer (PABC), with a special focus on diagnostic delays and the identifiable causes of diagnostic delays.

PATIENTS AND METHODS: Clinicopathological data of patients treated for PABC between 2003 and 2012 at Hacettepe University Hospital was retrospectively reviewed.

RESULTS: 20 patients with PABC were included. The pathological examination revealed predominance of invasive ductal carcinoma (80%), grade III tumors (65%) and advanced-stage (III-IV) disease (75%). In 8 patients (40%), there was a diagnostic delay between occurrence of the presenting symptoms and the initiation of breast mass workup. For these 8 patients, the main identifiable causes of diagnostic delay were the attribution of disease-related symptoms to pregnancy or lactation in 5 (63%) and negligence of symptoms in 2 (25%).

CONCLUSIONS: PABC mostly presents with advanced-stage disease, and there can be a substantial diagnostic delay before these patients receive treatment. Preconceptional, gestational and postpartum examination of women of reproductive age should include a thorough breast examination and should provide adequate information regarding the physiological changes in breast tissue and the possible pathological symptoms.}, } @article {pmid25758809, year = {2015}, author = {Kurebayashi, J and Miyoshi, Y and Ishikawa, T and Saji, S and Sugie, T and Suzuki, T and Takahashi, S and Nozaki, M and Yamashita, H and Tokuda, Y and Nakamura, S}, title = {Clinicopathological characteristics of breast cancer and trends in the management of breast cancer patients in Japan: Based on the Breast Cancer Registry of the Japanese Breast Cancer Society between 2004 and 2011.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {22}, number = {3}, pages = {235-244}, doi = {10.1007/s12282-015-0599-6}, pmid = {25758809}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology/*therapy ; Combined Modality Therapy ; Disease Management ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Japan ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Registries ; Young Adult ; }, abstract = {PURPOSES: We conducted a study to analyze the clinicopathological characteristics of breast cancer in Japan registered to the Japanese Breast Cancer Registry of the Japanese Breast Cancer Society (JBCS). Trends in the management of breast cancer patients in Japan were also analyzed.

PATIENTS AND METHODS: More than 250,000 breast cancer patients were registered to the JBCS registry between 2004 and 2011. Demographic and clinicopathological factors in newly diagnosed primary breast cancer patients were registered to the JBCS through the Web-based system from affiliated institutes nationwide.

RESULTS: Two distinct peaks were observed, in patients in their late 40s and early 60s, in the population-adjusted age distribution of breast cancer patients. An increased rate of screen-detected breast cancer may contribute to an earlier detection of breast cancer and increased rate of non-invasive ductal carcinoma. The positive rate of either ER or PgR appears to have increased in recent years. The annual rates of patients treated with breast-conserving surgery increased until 2006, but these increases stopped in 2007 and thereafter plateaued at approximately 60 %. The annual rates of patients treated with sentinel lymph node dissection alone have steadily increased. The annual rates of patients treated with preoperative trastuzumab plus chemotherapy have also increased, as well as those treated with postoperative aromatase inhibitors. The annual rates of patients treated with postoperative anthracycline-containing regimens have decreased, whereas those treated with postoperative taxane-containing regimens have increased. The postoperative use of trastuzumab has markedly increased since 2007.

CONCLUSION: Although this study was based on the registry database, several unique clinicopathological characteristics of breast cancer in Japan have been unveiled. Our results suggest that recent trends in the management of breast cancer patients in Japan were strongly followed by clinical evidence that originated from a number of clinical trials worldwide.}, } @article {pmid25758675, year = {2015}, author = {Blaschke, E and Abe, H}, title = {MRI phenotype of breast cancer: Kinetic assessment for molecular subtypes.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {42}, number = {4}, pages = {920-924}, doi = {10.1002/jmri.24884}, pmid = {25758675}, issn = {1522-2586}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Computer Simulation ; Contrast Media/pharmacokinetics ; Female ; Gadolinium DTPA/*pharmacokinetics ; Humans ; Image Interpretation, Computer-Assisted/methods ; Kinetics ; Magnetic Resonance Imaging/*methods ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Phenotype ; Precision Medicine/methods ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; }, abstract = {PURPOSE: To evaluate the dynamic contrast-enhanced magnetic resonance imaging (MRI) kinetic characteristics of newly diagnosed breast cancer molecular subtypes.

MATERIALS AND METHODS: Breast MRI examinations of 112 patients with newly diagnosed breast cancer were reviewed. Cases of newly diagnosed invasive ductal carcinoma were sorted by molecular subtype (28 TN, 11 HER2 +, 73 Lum A/B) and MRI field strength, with lesion segmentation and kinetic analyses performed on a dedicated workstation. For kinetic assessment, 50% and 100% thresholds were employed for display of medium and rapid uptake. Kinetic profiles in terms of percent volume for six kinetic types (medium-persistent, medium-plateau, medium-washout, fast-persistent, fast-plateau, fast-washout) relative to the whole volume of the lesion were obtained. Statistical analysis of the kinetic profiles was performed using Welch's t-test.

RESULTS: Percent volume of HER2-positive lesions with >100% uptake at early phase on 3T strength MRI exams was significantly greater compared with luminal A/B (93.8 ± 0.92 vs. 77.3 ± 7.2; P < 0.01) and triple negative (93.8 ± 0.92 vs. 81.3 ± 8.2; P < 0.05) subtypes. The >50% early phase uptake for HER2+ lesions was also higher than Lum A/B (99.1 ± 0.73 vs. 93.6 ± 3.05; P < 0.01) at 3T. In the 1.5T subgroup the percent volume of HER2+ tumors with >50% and >100% early phase uptake trended higher than Lum A/B lesions without reaching significance.

CONCLUSION: The percent volume of HER2-positive tumors demonstrating rapid early contrast uptake is significantly increased compared to other molecular subtypes.}, } @article {pmid25757345, year = {2014}, author = {Sakamoto, N and Maki, T and Kobayashi, S and Kobayashi, T and Hamaguchi, M and Yoshikawa, M and Iguchi, A and Momosaki, S and Nakayama, Y}, title = {[Distribution of intraductal carcinoma of the prostate and associated lesions in the cancer foci on radical prostatectomy specimens].}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {105}, number = {4}, pages = {163-70; discussion 171}, doi = {10.5980/jpnjurol.105.163}, pmid = {25757345}, issn = {0021-5287}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*pathology ; Humans ; Male ; Neoplasm Invasiveness ; Neoplasm Staging ; Prostatectomy ; Prostatic Neoplasms/*pathology ; }, abstract = {OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens.

MATERIALS AND METHODS: We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma.

RESULTS: We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma.

CONCLUSIONS: The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.}, } @article {pmid25753593, year = {2015}, author = {Xiao, M and Jiang, Y and Zhu, Q and You, S and Li, J and Wang, H and Lai, X and Zhang, J and Liu, H and Zhang, J}, title = {Diffuse optical tomography of breast carcinoma: can tumor total hemoglobin concentration be considered as a new promising prognostic parameter of breast carcinoma?.}, journal = {Academic radiology}, volume = {22}, number = {4}, pages = {439-446}, doi = {10.1016/j.acra.2014.12.012}, pmid = {25753593}, issn = {1878-4046}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast/blood supply/metabolism/pathology ; Breast Neoplasms/blood supply/diagnostic imaging/*metabolism ; Female ; Hemoglobins/*metabolism ; Humans ; Middle Aged ; Neovascularization, Pathologic ; Prognosis ; Prospective Studies ; *Tomography, Optical ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {RATIONALE AND OBJECTIVES: Diffuse optical tomography (DOT) is an emerging functional modality, which can reflect tumor metabolic activity and angiogenesis. The purpose of this exploratory study was to correlate the total hemoglobin concentration (THC) measured by noninvasive DOT with prognostic factors in breast carcinomas.

MATERIALS AND METHODS: We prospectively imaged 251 breast carcinomas in 229 consecutive women (mean age, 51.18 ± 12.32 years) using DOT from 2007 to 2010. Tumor angiogenesis and metabolic activity were assessed based on quantitatively measured THC. The THC was correlated with prognostic factors, including tumor size, histopathologic classification, histologic grade, estrogen receptor (ER), progesterone receptor (PR), c-erbB-2, and p53.

RESULTS: In univariate analysis, THC was significantly correlated with the following prognostic factors: tumor size (P < .001), histologic grade (P < .001), ER (P < .05), PR (P < .001), and c-erbB-2 (P < .05). THC was not associated with histopathologic classification (P = .170) or p53 (P = .463). On the basis of a stepwise multiple regression analysis, THC of invasive ductal carcinoma was significantly correlated with tumor size (P < .001), histologic grade (P < .001), and PR (P < .05).

CONCLUSIONS: THC was associated with prognostic factors of breast carcinoma. THC may be considered as a new prognostic parameter of breast carcinoma and a prediction of tumor behavior and biological activity.}, } @article {pmid25753457, year = {2015}, author = {Santangelo, G and Vitale, C and Picillo, M and Cuoco, S and Moccia, M and Pezzella, D and Erro, R and Longo, K and Vicidomini, C and Pellecchia, MT and Amboni, M and Brunetti, A and Salvatore, M and Barone, P and Pappatà, S}, title = {Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients.}, journal = {Parkinsonism & related disorders}, volume = {21}, number = {5}, pages = {489-493}, doi = {10.1016/j.parkreldis.2015.02.015}, pmid = {25753457}, issn = {1873-5126}, mesh = {Aged ; Apathy/*physiology ; Cohort Studies ; Corpus Striatum/*diagnostic imaging/*metabolism ; Dopamine Plasma Membrane Transport Proteins/*metabolism ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*diagnostic imaging/*metabolism ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon/methods ; }, abstract = {INTRODUCTION: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression.

METHODS: Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake.

RESULTS: PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate.

CONCLUSIONS: Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD.}, } @article {pmid25752197, year = {2015}, author = {Simpson, K and Jones, RE and Grimstead, JW and Hills, R and Pepper, C and Baird, DM}, title = {Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.}, journal = {Molecular oncology}, volume = {9}, number = {6}, pages = {1186-1193}, pmid = {25752197}, issn = {1878-0261}, support = {C17199/A13490//Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/genetics/*metabolism/*mortality/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Survival Rate ; Telomere/genetics/*metabolism ; *Telomere Homeostasis ; }, abstract = {Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.}, } @article {pmid25751500, year = {2015}, author = {Son, CH and Bae, JH and Lee, HR and Shin, DY and Yang, K and Park, YS}, title = {Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and CD25-targeted antibody for transplanted Lewis lung carcinoma cells.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {38}, number = {3}, pages = {107-115}, doi = {10.1097/CJI.0000000000000068}, pmid = {25751500}, issn = {1537-4513}, mesh = {Animals ; Antibodies, Monoclonal/*administration & dosage ; Antineoplastic Agents/*administration & dosage ; Apoptosis/drug effects/radiation effects ; Carcinoma, Lewis Lung/*immunology/mortality/pathology/therapy ; Cell Line, Tumor ; Combined Modality Therapy ; Cyclophosphamide/*administration & dosage ; Cytotoxicity, Immunologic/drug effects/radiation effects ; Dendritic Cells/*immunology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Immunophenotyping ; Immunosuppressive Agents/administration & dosage ; Immunotherapy ; Interleukin-2 Receptor alpha Subunit/*antagonists & inhibitors ; Male ; Mice ; Phenotype ; Radiation ; Spleen/immunology ; T-Lymphocytes, Regulatory/drug effects/immunology/metabolism/radiation effects ; Th1 Cells/drug effects/immunology/metabolism/radiation effects ; Tumor Microenvironment/drug effects/immunology/radiation effects ; }, abstract = {Regulatory T cells (Tregs) is one of the main obstacles to the success of cancer immunotherapy. The effect of dendritic cell (DC)-based immunotherapy can be attenuated by immune suppressive functions of Tregs. We used a CD25-targeted antibody and low-dose cyclophosphamide (CTX) as immunomodulators to increase the antitumor effect of intratumoral injection of immature DCs into the irradiated tumor cells (IR/iDC). CTX or CD25-targeted antibody alone showed a significant reduction in the number of Tregs within the tumor microenvironment. When they are combined with IR/iDC, the number of Tregs was further reduced. Although IR/IDC showed strong antitumor effects such as reduction in tumor growth, increase in Th1 immune response, and improvement of survival, the therapeutic effect was further improved by combining treatments with immunomodulators. CTX and CD25-targeted antibody showed no significant difference in tumor growth when combined with IR/iDC, but CTX further increased the number of interferon (IFN)-γ-secreting T cells, cytotoxicity, and survival rate. Although irradiation induced depletion of T lymphocytes, administration of DCs recovered this depletion. Particularly, the lymphocytes were more significantly increased when CTX and IR/iDC were combined. Low-dose CTX has already been used as an immunomodulator in clinical trials, and it offers several advantages, including convenience, low-cost, and familiarity to clinicians. However, CD25-targeted antibody cannot only deplete Tregs, but also may affect IL-2-dependent effector T lymphocytes. Therefore, CTX is an effective means to inhibit Tregs, and an effective immunomodulatory agent for multimodality therapy such as combination treatment of conventional cancer therapy and immunotherapy.}, } @article {pmid25750340, year = {2015}, author = {Arfaoui, A and Douik, H and Kablouti, G and Chaaben, AB and Handiri, N and Zid, Z and Ouni, N and Zouiouch, F and Ayari, F and Mamoughli, T and Bouassida, J and Abazza, H and Harzallaha, L and Guemira, F}, title = {Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.}, journal = {Anticancer research}, volume = {35}, number = {3}, pages = {1763-1769}, pmid = {25750340}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/etiology/*genetics ; Case-Control Studies ; *Codon ; *Drug Resistance, Neoplasm ; Female ; Genetic Predisposition to Disease ; Humans ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the possible association of p53 codon72 polymorphism with the breast cancer risk and resistance to anthracycline-based chemotherapy.

PATIENTS AND METHODS: Case-control study: This study enrolled 175 patients with breast cancer treated at the Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity and origin), used as a control, with no clinical evidence of any neoplastic disorder. Case-Case study: 400 breast cancer patients, with invasive ductal carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was isolated from whole-blood leucocytes using the phenol-chloroform method. Anthracycline response was scored according to the World Health Organization (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed using the Chi-square test.

RESULTS: Clinical data revealed that among the 400 patients, one quarter was resistant to chemotherapy treatment. Genetic data revealed that the p53 Arg72Pro genotype was found to be greatly associated with breast cancer risk (p<0.001), as well as tumor site (p=0.046). However, resistance to anthracycline-based chemotherapy does not seem to be correlated with p53 codon72 polymorphism in our population. Also, the distribution of tumor size, lymph node involvement and tumor grade was not significantly different among the polymorphic variants.

CONCLUSION: We conclude that p53 codon72 polymorphism is involved in susceptibility to developing breast cancer. It may be a factor of progression when breast sites are taken into account. However, there is no evidence indicating that Arg72Pro SNP may influence response to anthracycline-based chemotherapy.}, } @article {pmid25741051, year = {2014}, author = {Bitencourt, AG and Lima, EN and Chojniak, R and Marques, EF and de Souza, JA and Graziano, L and Andrade, WP and Osório, CA}, title = {Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas.}, journal = {Radiologia brasileira}, volume = {47}, number = {2}, pages = {67-73}, pmid = {25741051}, issn = {0100-3984}, abstract = {OBJECTIVE: To correlate the results of (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients.

MATERIALS AND METHODS: Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data.

RESULTS: The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm). Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%). At PET/CT, 53 (89.8%) of the lesions demonstrated anomalous concentrations of (18)F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5). A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression.

CONCLUSION: PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas.}, } @article {pmid25740670, year = {2015}, author = {Mioni, G and Zakay, D and Grondin, S}, title = {Faster is briefer: The symbolic meaning of speed influences time perception.}, journal = {Psychonomic bulletin & review}, volume = {22}, number = {5}, pages = {1285-1291}, pmid = {25740670}, issn = {1531-5320}, mesh = {Acceleration ; Adult ; *Attention ; Female ; Humans ; *Judgment ; Male ; Motion Perception ; Recognition, Psychology ; *Symbolism ; *Time Perception ; Visual Perception ; Young Adult ; }, abstract = {The present study investigates how the symbolic meaning of the stimuli presented for marking time intervals affects perceived duration. Participants were engaged in a time bisection task in which they were first trained with two standard durations, 400 ms and 1600 ms, and then asked to judge if the following temporal intervals were closer to the short or to the long standard. Stimuli were images of vehicles representing speed, with a motorbike representing fastness and a bicycle representing slowness. Results showed that presenting images with different speed meanings affects time perception: an image representing a fast object, the motorbike, leads to shorter perceived time than presenting an image representing a slower object, the bicycle. This finding is attributed to an impact on the memory mechanism involved in the processing of temporal information.}, } @article {pmid25737181, year = {2015}, author = {Nwashilli, NJ and Ugiagbe, EE}, title = {Bilateral synchronous male breast cancer.}, journal = {Saudi medical journal}, volume = {36}, number = {3}, pages = {359-362}, pmid = {25737181}, issn = {1658-3175}, mesh = {Aged ; Breast Neoplasms, Male/*diagnosis/pathology/surgery ; Humans ; Male ; Mastectomy ; }, abstract = {Bilateral synchronous breast cancer is extremely rare. A 75-year-old man presented with a right breast mass, which ulcerated and a lump in the left breast. Right breast examination revealed a breast ulcer 7x10cm with everted edges and complete nipple destruction. The left breast showed a hard lump measuring 4x5cm in the nipple-areolar area, unattached to skin, or underlying structure. There was no palpable axillary lymph node bilaterally. A wedge biopsy of right breast ulcer and excision of the left breast lump confirmed bilateral invasive ductal carcinoma - Grade 2 tumor in both breasts. He had bilateral simple mastectomy and chemotherapy; defaulted for 18 months during treatment, and re-presented with bilateral tumor recurrence. The importance of this case report is to create more awareness that breast cancer can occur in males just as in females, though the incidence is rare in males. Early presentation and compliance with treatment modality provide a better outcome.}, } @article {pmid25736840, year = {2015}, author = {Cherbal, F and Gaceb, H and Mehemmai, C and Saiah, I and Bakour, R and Rouis, AO and Boualga, K and Benbrahim, W and Mahfouf, H}, title = {Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study.}, journal = {Breast disease}, volume = {35}, number = {2}, pages = {95-102}, doi = {10.3233/BD-150398}, pmid = {25736840}, issn = {1558-1551}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Algeria ; Black People ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*metabolism/pathology ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. Molecular classification of breast cancer is an important factor for prognosis and clinical outcome. There are limited data regarding molecular breast cancer subtypes among Algerian women. The objective of the present study was to analyze the proportion and distribution of molecular subtypes and to determine their associations with some clinical and tumor characteristics: age at diagnosis, menopausal status, histological type and histological grade.

MATERIALS AND METHODS: The study population included 3014 female breast cancers. We analyzed breast cancers from cancer registries of academic medical oncology service of public hospital of Rouiba, anticancer center of Blida, and anticancer center of Batna. Breast cancers were diagnosed between 2008 and 2013. Molecular subtype classification was done based on immunohistochemical surrogates for ER (Estrogen receptor), PR (Progesterone receptor) and HER2 (human epidermal growth factor receptor-2) status obtained from medical records for 3014 breast cancer patients. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), TNBC (ER-, PR - , HER2-), HER2+ (ER-, PR-, HER2+). Molecular subtypes were correlated with the clinicopathological characteristics of the tumors.

RESULTS: The mean age at diagnosis cancer was 48.5 years. Proportions of the luminal A, TNBC, luminal B and HER2+ breast cancer subtypes were 50.59%, 20.80%, 19.67% and 8.92%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P= 0.004). Luminal A, Luminal B, TNBC and HER2+ subtypes were significantly different by premenopausal and postmenopausal status (P= 0.01). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes.

CONCLUSIONS: For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.}, } @article {pmid25731466, year = {2014}, author = {Miyazawa, K and Yoshioka, S and Shiobara, M and Wakatsuki, K and Kataoka, M and Arai, S and Yamazaki, K}, title = {[Long-term survival following postoperative combined modality therapy for pancreatic cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {2190-2192}, pmid = {25731466}, issn = {0385-0684}, mesh = {Aged ; Carcinoma, Ductal/*therapy ; Catheter Ablation ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Liver Neoplasms/secondary/therapy ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*therapy ; Recurrence ; Time Factors ; }, abstract = {A 69-year-old woman with back pain underwent distal pancreatectomy with left adrenectomy for advanced pancreatic cancer pathologically diagnosed as poorly differentiated invasive ductal carcinoma with retroperitoneal and perineural invasion, pT3N0M0, Stage III. The patient received adjuvant chemotherapy with S-1 for 6 months. However, 3 years after surgery, computed tomography (CT) revealed para-aorticlymph node (LN) recurrence. Treatment with gemcitabine (GEM) was begun and continued for 3 years. Following progression of the LN recurrence 5 and half years after surgery, administration of radiotherapy reduced diarrhea and back pain. Supportive care combined with radio-frequency ablation(RFA)was provided for multiple liver metastasis 5 years 7 months after surgery. The patient died due to gastrointestinal hemorrhage 6 years after surgery. We report long-term postoperative survival of a patient with recurrent pancreatic cancer following combined modality therapy.}, } @article {pmid25731457, year = {2014}, author = {Sui, K and Niguma, T and Yamada, M and Kojima, T and Mimura, T}, title = {[A case of a patient who underwent resection of the remnant pancreatic cancer following a distal pancreatectomy for invasive ductal carcinoma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {2163-2165}, pmid = {25731457}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*surgery ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual/surgery ; Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; }, abstract = {Herein, we report the case of a patient who underwent resection of the remnant pancreas for pancreatic cancer following a distal pancreatectomy for invasive ductal carcinoma. An 81-year-old woman underwent a distal pancreatectomy. The tumor was found to be pancreatic cancer. The tumor was histologically diagnosed as a poorly differentiated tubular adenocarcinoma (Stage I). An abdominal computed tomography (CT) performed 17 months later revealed a 13 mm tumor in the remnant pancreatic head. A remnant pancreatectomy was performed. The histological diagnosis was a moderately differentiated tubular adenocarcinoma (StageIII). Remnant pancreatic cancer is rare following a pancreatectomy for invasive ductal carcinoma. The course of remnant pancreatic cancer can be followed with imaging. Long-term follow-up of patients who have undergone a pancreatectomyis, therefore, essential.}, } @article {pmid25731396, year = {2014}, author = {Hayashi, K and Oshida, S and Nemoto, K and Habiro, T and Sengoku, N and Tanino, H and Watanabe, M}, title = {[Determination of treatment strategies for a 43-year-old single woman with Stage IV breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1981-1984}, pmid = {25731396}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/drug therapy/*secondary ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {The patient was a 43-year-old single woman. Her family history included schizophrenia in her mother and manic-depression in her father. Remicade® (infliximab) had been administered for 3 years to treat rheumatoid arthritis. The patient initially presented to our hospital with dyspnea. Computed tomography revealed left-sided breast cancer associated with multiple bone tumors and multiple pulmonary nodules. A poorly mobile mass with an ulcer was found in left breast. Core-needle biopsy and fluorescent in situ hybridization (FISH)revealed an invasive ductal carcinoma that was positive for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2, 2 +). The clinical diagnosis was Stage IV T4bN3M1 cancer (metastases to the lungs, liver, and bone). Because of the presence of bone metastasis, the patient was admitted and she received complete bed rest as supportive therapy. However, the patient decided to receive treatment on an outpatient basis after carefully discussing the following points: 1) treatment of pulmonary metastasis with dyspnea should receive priority; 2) anticancer agents not causing nausea were required; 3) the risk of bone fractures as a complication (spinal cord injury); 4) how she wanted to spend the limited time available with her family; and 5) how the patient wanted to.}, } @article {pmid25731395, year = {2014}, author = {Yabe, N and Murai, S and Kunugi, C and Nakadai, J and Oto, I and Yoshikawa, T and Kitasato, K and Shimizu, H and Nakamura, A and Masuda, A and Miyazaki, Y and Ohashi, M and Jinno, H and Kitagawa, Y}, title = {[Synchronous male bladder cancer and breast cancer - a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1978-1980}, pmid = {25731395}, issn = {0385-0684}, mesh = {*Adenocarcinoma, Scirrhous/drug therapy/secondary/surgery ; Aged ; *Breast Neoplasms/drug therapy/pathology/surgery ; *Breast Neoplasms, Male/drug therapy/pathology/surgery ; Humans ; Lymphatic Metastasis ; Male ; *Neoplasms, Multiple Primary/drug therapy/surgery ; Sentinel Lymph Node Biopsy ; *Urinary Bladder Neoplasms/drug therapy/pathology/surgery ; }, abstract = {A 74-year-old man complained of blood in his urine over a 1-week period beginning in early October 2013, and was examined in the urology department of our hospital. A thorough examination revealed bladder cancer, and surgery was planned after two cycles of preoperative gemcitabine plus cisplatin chemotherapy. A chest computed tomography (CT) performed to evaluate the response to chemotherapy revealed a mass in the right breast. The patient had previously complained about the same site, and mammography and ultrasonography had suggested the possibility of a malignant mammary gland tumor. The results of aspiration cytology were Class V, and based on that finding, a diagnosis of cancer of the right breast was made. In February 2014, we performed a mastectomy, while preserving the pectoral muscles, along with sentinel node biopsy, total cystectomy, urethrectomy, pelvic lymph node dissection, and ureteroileal anastomosis. The histopathological diagnosis of the right breast tumor was invasive ductal carcinoma[scirrhous carcinoma, ly (+), v (-), g (+), f (+), s (+), nuclear grade 1=atypia 2+mitosis 1, EIC (-), ICT (-), NCAT (-)]. A micrometastatic tumor measuring approximately 1mm was observed in the sentinel lymph node. The breast disease was classified as pT1N1mi(sn)M0, Stage IIA, and the tumor was ER (+), PgR (+), HER2/neu (2+), and FISH (-). The bladder cancer was diagnosed as urothelial carcinoma, non-papillary, invasive G2>G3, pT2a; no pelvic lymph node metastases were detected, and it was classified as pT2aN0M0, Stage II. Synchronous male breast cancer and bladder cancer is a very rare condition, and we report the case with a review of the literature.}, } @article {pmid25731391, year = {2014}, author = {Nagashima, S and Sakurai, K and Suzuki, S and Sakagami, M and Enomoto, K and Amano, S and Koshinaga, T}, title = {[Synchronous and ipsilateral invasive ductal carcinoma of the breast occurring near a phyllodes tumor - a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1965-1968}, pmid = {25731391}, issn = {0385-0684}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/surgery ; *Carcinoma, Ductal, Breast/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoplasms, Multiple Primary/pathology/surgery ; *Phyllodes Tumor/surgery ; }, abstract = {We report 2 cases of invasive ductal carcinoma of the breast occurring near a phyllodes tumor. The first case was ofa 58- year-old woman who had a tumor in her right breast and visited our hospital. Following a core needle biopsy (CNB), a malignant phyllodes tumor was diagnosed. We performed a lumpectomy for the phyllodes tumor, with 1.5-cm surgical margins. Pathological diagnosis of the resected specimen confirmed the malignant phyllodes tumor. A ductal carcinoma in situ (DCIS) was also discovered near the phyllodes tumor. The second case was of another 58-year-old woman who had a big tumor in her right breast and visited our hospital. CNB resulted in pathological diagnosis ofa benign phyllodes tumor. The tumor was removed by a lumpectomy with 1.5-cm surgical margins. The pathological diagnosis from the resected specimen was borderline phyllodes tumor with invasive ductal carcinoma in the proximity. In both cases, DCIS could not have been diagnosed preoperatively.}, } @article {pmid25731387, year = {2014}, author = {Tsubota, Y and Sueoka, N and Yamamoto, D}, title = {[A complete response following treatment with Paclitaxel and bevacizumab for metastatic breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1954-1956}, pmid = {25731387}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration & dosage ; Remission Induction ; }, abstract = {A 60-year-old woman with left breast cancer underwent partial mastectomy and sentinel lymph node biopsy. Pathological examination revealed an invasive ductal carcinoma that was ER (+), PgR (-), HER2 (-), and node positive (1/1). She received adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC), followed by weekly paclitaxel (PTX). After receiving radiation therapy, she was administered an aromatase inhibitor for 5 years. Six months after completion of therapy, she found a hard lymph node in the left infraclavicular area. Fine needle aspiration cytology of the lymph node indicated metastatic breast cancer. Fulvestrant was administered but disease progression was observed after 3 months. Systemic chemotherapy with PTX and bevacizumab (Bev) was begun. After 3 cycles of chemotherapy, computed tomography (CT) scan revealed a complete response (CR). After 6 cycles of chemotherapy, the CR has been maintained.}, } @article {pmid25731373, year = {2014}, author = {Sakurai, K and Fujisaki, S and Nagashima, S and Maeda, T and Tomita, R and Suzuki, S and Hara, Y and Hirano, T and Enomoto, K and Amano, S}, title = {[Usefulness of reductive surgery for elderly advanced breast cancer with bone metastases - a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1912-1914}, pmid = {25731373}, issn = {0385-0684}, mesh = {Adenocarcinoma, Mucinous/drug therapy/secondary/*surgery ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/*drug therapy/secondary ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/secondary/*surgery ; Combined Modality Therapy ; Female ; Humans ; }, abstract = {We report the case of an elderly, advanced breast cancer patient with multiple bone metastases. Breast reduction surgery was useful for this patient. The patient was an 81-year-old woman who had a breast lump. A core needle biopsy for breast cancer led to a diagnosis of invasive ductal carcinoma. The mucinous carcinoma was estrogen receptor (ER) nd progesterone receptor (PgR) positive and HER2/neu negative. Due to patient complications, it was not possible to treat with chemotherapy. The patient was administrated aromatase inhibitors (AI) and zoledronic acid hydrate. However, the AI treatment was not effective, and so she was administered toremifene. Toremifene treatment was effective for 6 months, after which she received fulvestrant. Fulvestrant treatment maintained stable disease (SD)for 14 months. After 14 months of fulvestrant treatment, serum concentrations of the tumor markers CA15-3, CEA, and BCA225 increased. We therefore decided to perform surgical breast reduction surgery. The pathological diagnosis from the surgically resected specimen was mucinous carcinoma, positive for ER and HER2, and negative for PgR. After surgery, serum concentrations of the tumor markers decreased. Following surgery, the patient was administrated lapatinib plus denosumab plus fulvestrant. The patient remains well, without bone metastases, 2 years and 6 months after surgery.}, } @article {pmid25731362, year = {2014}, author = {Kakimoto, M and Nakata, T and Imaizumi, K and Hirano, T and Yamamoto, Y and Chikatani, K and Hoshino, M and Matsuyama, T and Motoyama, K and Goto, H and Yoshimura, T and Koshiishi, H and Tsuruta, K}, title = {[A case of locally recurrent breast cancer difficult to differentiate from nodular fasciitis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1881-1883}, pmid = {25731362}, issn = {0385-0684}, mesh = {Aged ; Breast Neoplasms/complications/pathology/*therapy ; Carcinoma, Ductal, Breast/complications/*therapy ; Combined Modality Therapy ; Fasciitis/*etiology ; Fatal Outcome ; Female ; Humans ; Neoplasm Recurrence, Local ; }, abstract = {Breast-conserving surgery was performed on a 78-year-old woman for left breast cancer 5 years previously (invasive ductal carcinoma, T1cN2M0, stage IIIA, ER[+], PR[-], HER2[-]). Chemotherapy, radiotherapy, and hormonal therapy were administered. A left subclavian tumor was detected, and an excisional biopsy was performed. Histological examination showed spindle cells, different from primary breast cancer histology, and nodular fasciitis was diagnosed negative cytokeratin and vimentin immunostaining results. After 12 months, a mass had developed in the same region, and reoperation was performed for resection. Similar spindle cells were observed, but they tested positive for cytokeratin. Carcinoma was diagnosed and thought to be locally recurrent breast cancer. Despite postoperative chemotherapy, the patient experienced bone and lung metastasis and a third local recurrence. She died 13 months following the last surgery. Recurrent breast cancer sometimes displays different histology from the initial cancer, and mimics stromal tumors in certain cases.}, } @article {pmid25731361, year = {2014}, author = {Suzuki, S and Sakurai, K and Nagashima, S and Hara, Y and Enomoto, K and Amano, S and Fujisaki, S}, title = {[A difficult diagnosis of asynchronous both side breast cancers].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {12}, pages = {1878-1880}, pmid = {25731361}, issn = {0385-0684}, mesh = {Breast Neoplasms/*pathology/therapy ; Chemoradiotherapy ; Female ; Fibroadenoma/*therapy ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Second Primary/*pathology/therapy ; Sentinel Lymph Node Biopsy ; }, abstract = {A 53-years-old woman was diagnosed with left breast cancer (T2N0M0, Stage IIA) and underwent breast conserving surgery and axillaryly mph nodes resection. She was administered 2 courses of chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) and received a total of 50 Gy of radiation therapy as adjuvant therapy. Ultrasonography of the right breast, performed 2 years after the first operation, detected a tumor 7 mm in diameter. A core needle biopsy of the tumor was performed. The pathological diagnosis was fibroadenoma. The patient's whole body was checked for metastatic legions, but none were found. Right axillary lymph node swelling was detected 9 years after her first operation, and a surgical biopsy was performed. Frozen section analysis indicated that it was metastasis from the breast cancer. A further surgical biopsy was performed on the right breast mass. Frozen section analysis indicated the tumor was invasive ductal carcinoma within a fibroadenoma. Breast conserving surgeryand axillaryly mph node dissection were performed for the right breast cancer. The final permanent pathological diagnosis of the right breast was invasive ductal carcinoma within fibroadenoma (T2N1M0, Stage IIB), negative for estrogen receptor, negative for progesterone receptor, and negative for epidermal growth factor receptor 2(ErbB-2). The patient was administered 3 courses of chemotherapy consisting of taxotere and cyclophosphamide (TC) and received a total of 50 Gy of radiation therapy. The patient is alive without metastases 3 years after the second surgery.}, } @article {pmid25721482, year = {2015}, author = {Stolfo, D and Merlo, M and Pinamonti, B and Poli, S and Gigli, M and Barbati, G and Fabris, E and Di Lenarda, A and Sinagra, G}, title = {Early improvement of functional mitral regurgitation in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {115}, number = {8}, pages = {1137-1143}, doi = {10.1016/j.amjcard.2015.01.549}, pmid = {25721482}, issn = {1879-1913}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Echocardiography, Doppler, Color ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging, Cine ; Male ; Middle Aged ; Mitral Valve Insufficiency/diagnosis/etiology/*physiopathology ; Prognosis ; *Recovery of Function ; Retrospective Studies ; Time Factors ; Ventricular Function, Left/*physiology ; Ventricular Remodeling/*physiology ; }, abstract = {The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.}, } @article {pmid25719777, year = {2015}, author = {Pérez Rodrigo, C and Morán Fagúndez, LJ and Riobó Serván, P and Aranceta Bartrina, J}, title = {Screeners and brief assessment methods.}, journal = {Nutricion hospitalaria}, volume = {31 Suppl 3}, number = {}, pages = {91-98}, doi = {10.3305/nh.2015.31.sup3.8757}, pmid = {25719777}, issn = {1699-5198}, mesh = {Feeding Behavior ; Guidelines as Topic ; Humans ; *Nutrition Assessment ; Nutrition Policy ; Reproducibility of Results ; Risk Assessment ; }, abstract = {In the last two decades easy-to-use simple instruments have been developed and validated to assess specific aspects of the diet or a general profile that can be compared with a reference dietary pattern as the Mediterranean Diet or with the recommendations of the Dietary Guidelines. Brief instruments are rapid, simple and easy to use tools that can be implemented by unskilled personnel without specific training. These tools are useful both in clinical settings and in Primary Health Care or in the community as a tool for triage, as a screening tool to identify individuals or groups of people at risk who require further care or even they have been used in studies to investigate associations between specific aspects of the diet and health outcomes. They are also used in interventions focused on changing eating behaviors as a diagnostic tool, for self-evaluation purposes, or to provide tailored advice in web based interventions or mobile apps. There are some specific instruments for use in children, adults, elderly or specific population groups.}, } @article {pmid25719776, year = {2015}, author = {Riobó Serván, P and Sierra Poyatos, R and Soldo Rodríguez, J and Gómez-Candela, C and García Luna, PP and Serra-Majem, L}, title = {Special considerations for nutritional studies in elderly.}, journal = {Nutricion hospitalaria}, volume = {31 Suppl 3}, number = {}, pages = {84-90}, doi = {10.3305/nh.2015.31.sup3.8756}, pmid = {25719776}, issn = {1699-5198}, mesh = {Aged/*physiology ; Aged, 80 and over ; Drinking ; Geriatric Assessment/*methods ; Humans ; Malnutrition/epidemiology ; *Nutrition Assessment ; Nutritional Sciences/*methods ; Nutritional Status ; Reproducibility of Results ; }, abstract = {The elderly population is increasing and it is well documented that may present some health problems related to nutritional intake. Both mental and physical impairments in the elderly may need specific adaptations to dietary assessment methods. But all self-report approaches include systematic and random errors, and under-reporting of dietary energy intake is common. Biomarkers of protein intake, as 24 hours urinary Nitrogen, may not be useful in elderly patients because of incontinence problems. Some micronutrients, like vitamin B12, have special importance in the elderly population. Also, measurement of fluid intake is also critical because elderly population is prone to dehydration. A detailed malnutrition status assessment should be included in the geriatric dietary history, and assessment. Body mass index (BMI) is not useful in the elderly, and it is important to evaluate functional status. Gait speed, handgrip strength using hand dynamometry can be used. Body Shape Index (ABSI) appears to be an accurate measure of adiposity, and is associated with total mortality. Further research is needed to clarify the best and simple methods to accurately estimate food and beverage fluid intake in the elderly population, and to evaluate nutritional and hidration status.}, } @article {pmid25714914, year = {2015}, author = {Mbongue, JC and Nicholas, DA and Zhang, K and Kim, NS and Hamilton, BN and Larios, M and Zhang, G and Umezawa, K and Firek, AF and Langridge, WH}, title = {Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0118562}, pmid = {25714914}, issn = {1932-6203}, support = {DK-99-013/DK/NIDDK NIH HHS/United States ; S10 RR027643/RR/NCRR NIH HHS/United States ; R25 GM060507/GM/NIGMS NIH HHS/United States ; 1S10RR027643/RR/NCRR NIH HHS/United States ; P20 MD006988/MD/NIMHD NIH HHS/United States ; 5P20MD006988/MD/NIMHD NIH HHS/United States ; }, mesh = {Cell Differentiation ; Cholera Toxin/genetics/*immunology ; Cluster Analysis ; Dendritic Cells/cytology/*immunology/*metabolism ; Gene Expression Profiling ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*biosynthesis/genetics ; Monocytes/cytology/metabolism ; NF-kappa B/metabolism ; Proinsulin/genetics/*immunology ; Proteome ; Proteomics ; Signal Transduction ; Vaccines, Subunit/genetics/*immunology ; }, abstract = {Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.}, } @article {pmid25714366, year = {2015}, author = {Medrikova, D and Sijmonsma, TP and Sowodniok, K and Richards, DM and Delacher, M and Sticht, C and Gretz, N and Schafmeier, T and Feuerer, M and Herzig, S}, title = {Brown adipose tissue harbors a distinct sub-population of regulatory T cells.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0118534}, pmid = {25714366}, issn = {1932-6203}, mesh = {Adipose Tissue, Brown/*immunology/metabolism/pathology ; Animals ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Inflammation/genetics/immunology/metabolism ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Mice ; Phenotype ; Spleen/cytology/immunology/metabolism ; T-Lymphocyte Subsets/*immunology/metabolism ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.}, } @article {pmid25713774, year = {2015}, author = {Dueñas, JP and Duque, CS and Herrera, MF}, title = {The current situation of Endocrine Surgery in Latin America.}, journal = {Gland surgery}, volume = {4}, number = {1}, pages = {3-7}, pmid = {25713774}, issn = {2227-684X}, abstract = {The management of patients with surgical endocrine diseases requires a multidisciplinary team of endocrinologists, radiologists, pathologists and surgeons. As the incidence of surgical endocrine disorders has increased, Endocrine Surgery has emerged as a recognized specialty within general surgery. The number of endocrine surgeons has gradually increased worldwide, however, different from Europe and North America, the specialty has not developed enough in Latin America. We have conducted an extensive research throughout the continent in order to quantify how many trained endocrine surgeons were practicing, how many training programs exist, where we are today and where are we going in the future.}, } @article {pmid25713666, year = {2014}, author = {Matsuda, Y and Yamada, Y and Ikuta, Y and Nomura, T and Oda, S}, title = {Intracyclic velocity variation and arm coordination for different skilled swimmers in the front crawl.}, journal = {Journal of human kinetics}, volume = {44}, number = {}, pages = {67-74}, pmid = {25713666}, issn = {1640-5544}, abstract = {The aim of this study was to examine whether the intracyclic velocity variation (IVV) was lower in elite swimmers than in beginner swimmers at various velocities, and whether differences may be related to arm coordination. Seven elite and nine beginner male swimmers swam front crawl at four different swimming velocities (maximal velocity, 75%, 85%, and 95% of maximal swimming velocity). The index of arm coordination (IDC) was calculated as the lag time between the propulsive phases of each arm. IVV was determined from the coefficient of variation of horizontal velocity within one stroke cycle. IVV for elite swimmers was significantly lower (26%) than that for beginner swimmers at all swimming velocities (p<0.01, 7.28 1.25% vs. 9.80 1.70%, respectively). In contrast, the IDC was similar between elite and beginner swimmers. These data suggest that IVV is a strong predictor of the skill level for front crawl, and that elite swimmers have techniques to decrease IVV. However, the IDC does not contribute to IVV differences between elite and beginner swimmers.}, } @article {pmid25713171, year = {2015}, author = {Cohen-Chen, S and Crisp, RJ and Halperin, E}, title = {Perceptions of a changing world induce hope and promote peace in intractable conflicts.}, journal = {Personality & social psychology bulletin}, volume = {41}, number = {4}, pages = {498-512}, pmid = {25713171}, issn = {1552-7433}, mesh = {Adult ; *Conflict, Psychological ; Female ; *Hope ; Humans ; Male ; Negotiating/*psychology ; *Social Perception ; Young Adult ; }, abstract = {The importance of hope in promoting conciliatory attitudes has been asserted in the field of conflict resolution. However, little is known about conditions inducing hope, especially in intractable conflicts, where reference to the outgroup may backfire. In the current research, five studies yielded convergent support for the hypothesis that hope for peace stems from a general perception of the world as changing. In Study 1, coders observed associations between belief in a changing world, hope regarding peace, and support for concessions. Study 2 revealed the hypothesized relations using self-reported measures. Studies 3 and 4 established causality by instilling a perception of the world as changing (vs. unchanging) using narrative and drawing manipulations. Study 5 compared the changing world message with a control condition during conflict escalation. Across studies, although the specific context was not referred to, the belief in a changing world increased support for concessions through hope for peace.}, } @article {pmid25710705, year = {2015}, author = {Moatamed, NA and Wu, A and Sarah, K and Apple, SK}, title = {Cytokeratin 7 negative invasive breast carcinoma: clinicopathological and immunohistochemical analysis of 14 cases with clinical follow-up.}, journal = {Journal of clinical pathology}, volume = {68}, number = {6}, pages = {484-487}, doi = {10.1136/jclinpath-2014-202729}, pmid = {25710705}, issn = {1472-4146}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; *Keratin-7 ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sentinel Lymph Node Biopsy ; }, abstract = {Cytokeratin 7 (CK 7) negative breast tumours are reported to occur rarely. We studied 14 CK 7 negative cases of primary invasive ductal carcinoma (IDC) detected during sentinel lymph node metastases work-up and immunohistochemistry panel in the work-up of metastatic carcinoma of unknown origin. Axillary lymph node metastases were present in seven patients (50%). Oestrogen receptor (ER) was strongly positive in all cases: progesterone receptor in 78%, Her-2/neu in 7% and high proliferation index with Ki-67 >20% was seen in 71% of the cases. Metastatic and/or recurrence were found in 8 of 14 patients (57%) with the mean clinical follow-up of 55 months. Metastatic sites include multiple bones, brain, spinal cord, liver, pancreas, ovary, lung, lymph node other than ipsilateral axillary and skin. 12 of 14 patients received adjuvant chemotherapy. All 14 patients received hormonal therapy and radiation therapy. Morphologically, IDC with neuroendocrine features was noted in 57%. Synaptophysin stain was positive in 57% and chromogranin was positive in 21% of the cases. In conclusion, these CK 7 negative breast carcinomas were ER positive, mostly Her-2/neu negative, had high Ki-67 and frequently showed neuroendocrine differentiation. More than half of these cases had a poor outcome.}, } @article {pmid25709550, year = {2015}, author = {Choudhery, S and Seiler, S}, title = {Positron Emission Mammography Imaging with Low Activity Fluorodeoxyglucose and Novel Utilization in Core-needle Biopsy Sampling.}, journal = {World journal of nuclear medicine}, volume = {14}, number = {1}, pages = {63-65}, pmid = {25709550}, issn = {1450-1147}, abstract = {Positron emission mammography (PEM), a relatively novel breast imaging modality, provides certain advantages over magnetic resonance imaging, including the ability to image biopsy samples. However, the radiation activity associated with PEM has remained a concern in clinical practice. We present a case of an invasive ductal carcinoma that was adequately imaged with a much lower than the standard 185 to 370 MBq activity of (18)F-fluorodeoxyglucose. In addition, we demonstrate ultrasound-guided core-needle biopsy sample imaging with PEM to assess adequacy of sampling, a strategy that has previously only been documented with vacuum-assisted biopsy samples.}, } @article {pmid25708664, year = {2015}, author = {Yıldız, N and Alkan, H and Sarsan, A and Alkan, S}, title = {The effects of repeated filling cystometries on cystometric variables in spinal cord-injured patients with overactive detrusor, who utilize different type of urine drainage methods.}, journal = {Spinal cord}, volume = {53}, number = {8}, pages = {625-629}, pmid = {25708664}, issn = {1476-5624}, mesh = {Adult ; Aged ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Spinal Cord Injuries/*complications ; Treatment Outcome ; Urinary Bladder, Overactive/*etiology/*therapy ; Urinary Catheterization/*methods ; Young Adult ; }, abstract = {STUDY DESIGN: Cross-sectional study.

OBJECTIVES: Our aim was to compare the effects of repeated cystometric measurements in spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO) who use indwelling catheters (IDC) or intermittent catheterization (IC).

SETTING: Turkey.

METHODS: A total of 20 SCI patients with NDO, 9 patients on IC and 11 on IDC for at least two consecutive months were included. After emptying the bladder, first involuntary detrusor contraction volume (1stIDCV), cystometric bladder capacity (CC), bladder compliance and maximum detrusor pressure (MPdet) were assessed by filling it with sterile physiological saline at room temperature at a continuous rate of 30 ml min(-1). The bladder was re-emptied after the process and a second filling cystometry was performed in the same way.

RESULTS: When all study population were taken into account, 1stIDCV and CC measures were significantly increased in the second cystometry compared with the first cystometry (P=0.001 and P=0.022, respectively), whereas there was no statistically significant difference on bladder compliance and MPdet measures between the first and the repeated cystometry. There was no statistically significant difference on 1stIDCV, CC and bladder compliance measures between the first and the repeated cystometries for IC group, whereas there was statistically significant increase on these measures in the IDC group (P=0.003, P=0.008 and P=0.022, respectively). In addition there was no statistically significant difference on MP(det) measures between the first and the repeated cystometries for both the urine drainage methods. When IC and IDC groups were compared according to mean values of differences in 1stIDCV, CC and bladder compliance measures between the two cystometries, the IDC group had a statistically significant increase in all parameters when compared with the IC group in the second cystometry performed (P=0.001, P=0.003 and P=0.048, respectively).

CONCLUSION: Repeated cystometric measurements in SCI patients with NDO lead to an increase in 1stIDCV and CC. However, when the type of urine drainage method is taken into account, although repeated filling cystometry leads to an increase in 1stIDCV, MCC and bladder compliance in patients with IDC, it does not cause a difference in patients on IC.}, } @article {pmid25703191, year = {2015}, author = {Akrivos, J and Ravona-Springer, R and Schmeidler, J and LeRoith, D and Heymann, A and Preiss, R and Hoffman, H and Koifman, K and Silverman, JM and Schnaider Beeri, M}, title = {Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes.}, journal = {International journal of geriatric psychiatry}, volume = {30}, number = {10}, pages = {1093-1100}, pmid = {25703191}, issn = {1099-1166}, support = {R01 AG034087/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Attention/physiology ; Biomarkers/analysis ; Blood Glucose/*physiology ; *C-Reactive Protein/analysis ; Cognition/*physiology ; Diabetes Mellitus, Type 2/*physiopathology ; Executive Function/physiology ; Female ; *Glycated Hemoglobin/analysis ; Humans ; Inflammation/blood/*physiopathology ; Israel ; Male ; Memory/physiology ; Middle Aged ; Regression Analysis ; Retrospective Studies ; }, abstract = {OBJECTIVE: Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes.

METHODS: A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization.

RESULTS: Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = -0.166, p = 0.011), executive functions (r = -0.136, p = 0.038), and overall cognition (r = -0.157, p = 0.016).

CONCLUSIONS: Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes.}, } @article {pmid25701854, year = {2015}, author = {Bai, AD and Showler, A and Burry, L and Steinberg, M and Ricciuto, DR and Fernandes, T and Chiu, A and Raybardhan, S and Science, M and Fernando, E and Tomlinson, G and Bell, CM and Morris, AM}, title = {Impact of Infectious Disease Consultation on Quality of Care, Mortality, and Length of Stay in Staphylococcus aureus Bacteremia: Results From a Large Multicenter Cohort Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {60}, number = {10}, pages = {1451-1461}, doi = {10.1093/cid/civ120}, pmid = {25701854}, issn = {1537-6591}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteremia/*mortality ; Cohort Studies ; Female ; Hospitals ; Humans ; *Length of Stay ; Male ; Middle Aged ; *Quality of Health Care ; Referral and Consultation/*statistics & numerical data ; Retrospective Studies ; Staphylococcal Infections/*mortality ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB).

METHODS: A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge.

RESULTS: Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2-4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52-.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06-1.56; P = .0109) for being discharged alive.

CONCLUSIONS: ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.}, } @article {pmid25700939, year = {2015}, author = {Rohilla, M and Bal, A and Singh, G and Joshi, K}, title = {Phenotypic and Functional Characterization of Ductal Carcinoma In Situ-Associated Myoepithelial Cells.}, journal = {Clinical breast cancer}, volume = {15}, number = {5}, pages = {335-342}, doi = {10.1016/j.clbc.2015.01.004}, pmid = {25700939}, issn = {1938-0666}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Epithelial Cells/*chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; Keratin-5/analysis ; Keratin-6/analysis ; Transcription Factors/analysis ; Tumor Suppressor Proteins/analysis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is contained by myoepithelial cells that are morphologically similar to normal breast tissue myoepithelial cells. However, phenotypic and functional characteristics of DCIS-associated myoepithelial cells are not known. In this study, we aimed to assess the characteristics of DCIS-associated myoepithelial cells.

MATERIALS AND METHODS: Immunophenotypic and functional characteristics of myoepithelial cells of pure DCIS, the DCIS component of infiltrating duct carcinoma (IDC), and the adjacent normal breast tissue of both groups (30 cases in each group) was assessed using phenotypic (CK5/6, CK14, p63, and calponin) and functional markers (maspin and CXCL14).

RESULTS: There was a decrease in expression of CK14, p63, and calponin in pure DCIS-associated myoepithelial cells compared with normal breast tissue myoepithelial cells (43.3% vs. 80.3%, 3.3% vs. 70%, 46.6 vs. 93.3%, respectively) and in the DCIS component of IDC compared with normal breast tissue myoepithelial cells (56.6% vs. 100%, 3.3% vs. 73.3%, 56.6% vs. 96.6%, respectively). CK5/6 expression was low to absent in myoepithelial cells of pure DCIS and the DCIS component of IDC as well as normal breast tissue myoepithelial cells. Maspin was expressed in all samples of normal breast tissue; however, 20% of pure DCIS and 26.6% of the DCIS component of IDC showed decreased expression. CXCL14 expression was greater in pure DCIS compared with adjacent normal breast tissue and the DCIS component of IDC.

CONCLUSION: Decreased expression of myoepithelial cell markers in DCIS suggests that DCIS-associated myoepithelial cells are phenotypically different from their normal counterparts. Two or more markers, preferably p63 and calponin, should be used to distinguish in situ from invasive breast carcinomas.}, } @article {pmid25697711, year = {2015}, author = {Moccia, M and Picillo, M and Erro, R and Allocca, R and Barone, P and Vitale, C}, title = {Diagnosis and treatment of restless legs syndrome in progressive supranuclear palsy.}, journal = {Journal of the neurological sciences}, volume = {350}, number = {1-2}, pages = {103-104}, doi = {10.1016/j.jns.2015.01.025}, pmid = {25697711}, issn = {1878-5883}, mesh = {Dopamine Agents/therapeutic use ; Humans ; Male ; Middle Aged ; Restless Legs Syndrome/complications/*diagnosis/*therapy ; Supranuclear Palsy, Progressive/complications/*diagnosis/*therapy ; Treatment Outcome ; }, abstract = {Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7-58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed.}, } @article {pmid25692431, year = {2015}, author = {Kitaguchi, K and Kato, Y and Kojima, M and Okubo, S and Takahashi, D and Okada, R and Nakayama, Y and Nishida, Y and Gotohda, N and Takahashi, S and Konishi, M}, title = {A resected case of intraductal tubulopapillary neoplasm of the pancreas: report of a case.}, journal = {International surgery}, volume = {100}, number = {2}, pages = {281-286}, pmid = {25692431}, issn = {2520-2456}, mesh = {Carcinoma, Ductal/diagnosis/metabolism/*surgery ; Cholangiopancreatography, Magnetic Resonance ; Humans ; Immunohistochemistry ; Keratin-7/analysis ; Male ; Middle Aged ; Pancreatic Neoplasms/diagnosis/metabolism/*surgery ; Pancreaticoduodenectomy ; Trypsin/analysis ; }, abstract = {The patient was a 61-year-old male who was referred to our hospital after dilatation of the main pancreatic duct was detected by screening ultrasonography. Computed tomography revealed a protruding lesion measuring 15 mm in diameter within the main pancreatic duct in the head of the pancreas, and magnetic resonance cholangiopancreatography revealed interruption of the duct at the tumor site. We performed pancreaticoduodenectomy under a suspected diagnosis of invasive ductal carcinoma. Gross examination of the resected specimen showed that the tumor invaginated into the main pancreatic duct, and no mucin was found. Histological examination revealed proliferation of high-grade dysplastic cells in a tubulopapillary growth pattern. Immunohistochemically, cytokeratin 7 expression was detected, but not trypsin expression. Based on these morphological features, we diagnosed the tumor as intraductal tubulopapillary neoplasm (ITPN). We report the case with bibliographic consideration, together with a review of intraductal neoplasms of the pancreas encountered at our institution.}, } @article {pmid25691085, year = {2015}, author = {Abouharb, S and Moulder, S}, title = {Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy.}, journal = {Current oncology reports}, volume = {17}, number = {3}, pages = {431}, pmid = {25691085}, issn = {1534-6269}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*therapeutic use ; *Breast Neoplasms/drug therapy/genetics/pathology/secondary ; *Carcinoma/drug therapy/genetics/pathology/secondary ; Diagnosis, Differential ; Female ; Humans ; Molecular Targeted Therapy/*methods ; Prognosis ; *Rare Diseases/drug therapy/genetics/pathology ; }, abstract = {Metaplastic breast cancer is a rare subtype of invasive mammary carcinoma, with an aggressive behavior and usually poor outcome. Responses to systemic chemotherapy are suboptimal compared to patients with standard invasive ductal carcinoma. Limited data are available in regards to best treatment modalities, including chemotherapy. This review gives an overview of metaplastic breast cancer and its clinical and pathologic characteristics, in addition to treatment strategies, clinical trials, and future directions.}, } @article {pmid25684532, year = {2015}, author = {Yan, J and Liu, XL and Han, LZ and Xiao, G and Li, NL and Deng, YN and Yin, LC and Ling, LJ and Yu, XY and Tan, CL and Huang, XP and Liu, LX}, title = {Relation between Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-α expression in invasive ductal breast cancer patients and correlations with prognosis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {16}, number = {2}, pages = {823-829}, doi = {10.7314/apjcp.2015.16.2.823}, pmid = {25684532}, issn = {2476-762X}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Cyclin-Dependent Kinase Inhibitor p21/*metabolism ; DNA Topoisomerases, Type II/*metabolism ; DNA-Binding Proteins/*metabolism ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen/*metabolism ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/metabolism/mortality/*pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Survival Rate ; Young Adult ; }, abstract = {The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-α in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-α, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-α, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-α. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-α, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.}, } @article {pmid25683252, year = {2015}, author = {Stover, CS}, title = {Fathers for Change for Substance Use and Intimate Partner Violence: Initial Community Pilot.}, journal = {Family process}, volume = {54}, number = {4}, pages = {600-609}, pmid = {25683252}, issn = {1545-5300}, support = {K23 DA023334/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Child, Preschool ; Cognitive Behavioral Therapy ; Counseling ; Family Characteristics ; Father-Child Relations ; Fathers/*psychology ; Humans ; Intimate Partner Violence/*prevention & control ; Male ; Object Attachment ; *Parenting ; *Paternal Behavior ; Patient Satisfaction ; Pilot Projects ; Substance-Related Disorders/prevention & control/*rehabilitation ; Young Adult ; }, abstract = {The lack of focus on the role of men as fathers within intervention programs for men with histories of Intimate Partner Violence (IPV) or substance abuse is of significant concern given the large numbers of these men who are actively parenting and coparenting children. Fathers for Change is a new intervention designed to fill this gap. Eighteen fathers with co-occurring IPV and substance abuse were randomly assigned to Fathers for Change or Individual Drug Counseling (IDC). They were assessed at baseline, post-intervention and 3 months following the 16-week intervention period. Men in the Fathers for Change group: (1) were more likely to complete treatment; (2) reported significantly greater satisfaction with the program; (3) reported a trend toward less IPV; and (4) exhibited significantly less intrusiveness in coded play interactions with their children following treatment than fathers in the IDC group. Results indicate further evaluation of this intervention in a larger sample is warranted. Limitations and directions for future research are discussed.}, } @article {pmid25671929, year = {2014}, author = {Akbar, M and Akbar, K and Naveed, D}, title = {Frequency and correlation of molecular subtypes of breast cancer with clinicopathological features.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {26}, number = {3}, pages = {290-293}, pmid = {25671929}, issn = {1025-9589}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Triple Negative Breast Neoplasms/chemistry/pathology ; Young Adult ; }, abstract = {BACKGROUND: Traditional clinicopathological classification of breast cancer has limitations as tumours with similar clinical and histological features behave differently regarding outcome and responsiveness to chemo/immunotherapy. The objectives of the study were to determine the frequency of different molecular subtypes of breast cancer based on immunohistochemical staining and to find the correlation of each subtype with clinicopathological features.

METHODS: Sixty patients with histologically diagnosed invasive ductal carcinoma were enrolled in this cross sectional study. Immunohistological staining of the tumour samples and based on receptor status tumours were classified in four subtypes, Luminal A, Luminal B, HER2/neu oncogene amplification subtype and Tripple negative subtype. Clinical features, stage of disease at presentation and histopathological grade of the tumours was also recoded in each subtype. Prevalence of each subtype was calculated and correlation with clinical and pathological features was determined.

RESULTS: Mean age of tli`S patients was 47.55 years. Protective role of breast feeding was not confirmed in this study as 58 (96.67%) patients breast fed their children. Only two (3.33%) patients gave family history of breast cancer in the study. Thirty three (55%) patients had grade 2 tumours, 26 (43.33%) had grade 3 tumours while only one patient had grade 1 tumour. HER2/neu amplification subtype was the most common molecular subclass in the study, comprising 30% of all the patients. Ten patients (16.67%) in this study belonged to triple negative group. Triple negative disease was found in younger women with mean age of 40-60 years.

CONCLUSION: Breast cancer particularly triple negative disease was found in younger age group and patients usually present in advanced stage of their disease.HER2fneu positive breast cancer was the most common subtype in this study.}, } @article {pmid25669901, year = {2015}, author = {Cooper, I and Last, D and Guez, D and Sharabi, S and Elhaik Goldman, S and Lubitz, I and Daniels, D and Salomon, S and Tamar, G and Tamir, T and Mardor, R and Fridkin, M and Shechter, Y and Mardor, Y}, title = {Combined local blood-brain barrier opening and systemic methotrexate for the treatment of brain tumors.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {35}, number = {6}, pages = {967-976}, pmid = {25669901}, issn = {1559-7016}, mesh = {Animals ; Antimetabolites, Antineoplastic/*administration & dosage/therapeutic use ; Blood-Brain Barrier/drug effects/pathology ; Brain/drug effects/*pathology ; Brain Neoplasms/*drug therapy/pathology ; Cell Line ; Convection ; Drug Delivery Systems/*methods ; Ethylamines/adverse effects/chemical synthesis/chemistry ; Glioma/*drug therapy/pathology ; Humans ; Male ; Methotrexate/*administration & dosage/therapeutic use ; Rats ; Rats, Inbred Lew ; Serum Albumin/adverse effects/chemical synthesis/chemistry ; Swine ; }, abstract = {Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood-brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically administered drug by the tumors own vasculature. Various human serum albumin (HSA) analogs were synthesized and screened for BBB disruption efficacy in custom in vitro systems. The candidate analogs were then delivered into naïve rat brains by convection-enhanced delivery and screened for maximal BBB disruption and minimal brain toxicity. These studies found a noncationized/neutralized analog, ethylamine (EA)-HSA, to be the optimal BBB-opening agent. Immunocytochemical studies suggested that BBB disruption by EA-HSA may be explained by alterations in occludin expression. Finally, an efficacy study in rats bearing intracranial gliomas was performed. The rats were treated by convection-enhanced delivery of EA-HSA in parallel to systemic administration of Methotrexate, showing significant antineoplastic effects of the combined approached reflected in suppressed tumor growth and significantly (~x3) prolonged survival.}, } @article {pmid25667653, year = {2015}, author = {Ma, ZS and Wang, DW and Sun, XB and Shi, H and Pang, T and Dong, GQ and Zhang, CQ}, title = {Quantitative analysis of 3-Tesla magnetic resonance imaging in the differential diagnosis of breast lesions.}, journal = {Experimental and therapeutic medicine}, volume = {9}, number = {3}, pages = {913-918}, pmid = {25667653}, issn = {1792-0981}, abstract = {The aim of this study was to investigate the value of quantitative 3-Tesla (3T) magnetic resonance (MR) assessment in the diagnosis of breast lesions. A total of 44 patients with breast lesions were selected. All the patients underwent MR plain scanning and T1 dynamic contrast-enhanced imaging. The vascular function parameters of the lesions, namely volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve) and integrated area under the curve (iAUC), were acquired. These parameters were compared between benign and malignant breast lesions, and also among differential grades of invasive ductal carcinoma. The values of Ktrans, Kep and iAUC were significantly different between the benign and malignant tumors; however, the values of Ve in the benign and malignant tumors were not significantly different. The values of Ktrans, Kep and iAUC in invasive ductal carcinoma were significantly different between grade I and grade II, and between grade I and grade III; however, there was no significant difference between grade II and grade III. The Ve values in invasive ductal carcinoma did not significantly differ among grades I, II and III. Among the vascular function parameters, Ktrans exhibited the highest sensitivity and specificity in the differentiation of benign and malignant lesions. Quantitative 3-T MR assessment is valuable in the diagnosis of benign and malignant breast lesions. It can also provide reference values for the differentiation of the histological grade of breast invasive ductal carcinoma.}, } @article {pmid25663874, year = {2015}, author = {Cui, ZQ and Feng, JH and Zhao, YJ}, title = {Clinicopathological features of invasive micropapillary carcinoma of the breast.}, journal = {Oncology letters}, volume = {9}, number = {3}, pages = {1163-1166}, pmid = {25663874}, issn = {1792-1074}, abstract = {The aim of the present study was to evaluate the clinical and immunohistopathological findings of invasive micropapillary carcinoma (IMPC) of the breast. In total, 25 patients were included in the present study, all of whom were diagnosed with IMPC. The mammography and ultrasound scanning (US) findings were analysed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. Surgical specimens obtained from the patients were microscopically reviewed in consensus by two pathologists with a specialisation in breast pathology. All the patients presented with palpable lumps in the breast, a high-density irregular mass associated with microcalcifications revealed by mammography and an irregular hypoechoic mass with a spiculated margin revealed by US. Axillary lymph node metastases were identified in 80% of the patients. Immunohistochemical studies revealed the lesions to be highly positive for the oestrogen receptor (ER) and c-erbB-2 (88% and 84%, respectively). Although no significant imaging characteristics were found to distinguish IMPC from typical invasive ductal carcinoma, IMPC resulted in nodal metastases and was highly positive for ER and c-erbB-2. This clinical significance indicates the significance of this entity being recognised by pathologists and surgeons.}, } @article {pmid25661681, year = {2015}, author = {Rodrigues, P and Hering, F and Cieli, E and D'Imperio, M and Campagnari, JC}, title = {Can We State Stable Bladder? How Many Repetitions Should We Do for an Appropriate Demonstration of Involuntary Detrusor Contraction?.}, journal = {Urologia internationalis}, volume = {95}, number = {1}, pages = {86-91}, doi = {10.1159/000370163}, pmid = {25661681}, issn = {1423-0399}, mesh = {Adult ; Aged ; Artifacts ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Muscle Contraction/*physiology ; Muscle Hypertonia/physiopathology ; Muscle, Smooth/pathology ; Pelvic Organ Prolapse/surgery ; Prospective Studies ; Recurrence ; Reproducibility of Results ; Temperature ; Urinary Bladder/*pathology ; Urinary Bladder, Overactive/*diagnosis ; Urinary Incontinence, Stress/*diagnosis ; Urinary Tract Infections/surgery ; Urination Disorders/*diagnosis/*physiopathology ; Urodynamics ; }, abstract = {AIMS: Involuntary Detrusor Contraction (IDC) may alter therapeutic plans; therefore, urodynamic demonstration (UD) is pivotal. We explore if same session repetitions enhance its demonstration and minimize false-negative results.

METHODS: Two hundred fifty two women (mean age 47 ± 5.7) had 4 full repetitions of UD with the last round filled with 4°C fluid (Ice-water test). IDC was diagnosed if with at least 3 cm H2O after artifacts were ruled out.

RESULTS: 44.4% of the cases showed IDC in the first round of the exam but it could be demonstrated in 88.5% of the women if 4 rounds are taken into account. Only 2 cases showed IDC exclusively in the first round. Nine cases (3.5%) showed IDC in the first round and only on Ice-test, while all other IDC-detected cases revealed it in scattered patterns along the repetitions. Likewise, IDC detection on the second, third and fourth rounds varied widely and unpredictably, many failing to show a consistent pattern of presentation after its detection. IDC wave amplitude did not show any correlation to the detection.

CONCLUSIONS: Urodynamic repetition is a necessary procedure where IDC is important to demonstrate, as its false-negative rate is high and its unpredictable pattern of detection may be improved by repetition.}, } @article {pmid25658358, year = {2015}, author = {Matsuda, Y and Ishiwata, T and Izumiyama-Shimomura, N and Hamayasu, H and Fujiwara, M and Tomita, K and Hiraishi, N and Nakamura, K and Ishikawa, N and Aida, J and Takubo, K and Arai, T}, title = {Gradual telomere shortening and increasing chromosomal instability among PanIN grades and normal ductal epithelia with and without cancer in the pancreas.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117575}, pmid = {25658358}, issn = {1932-6203}, mesh = {Carcinoma in Situ/genetics/metabolism/*pathology ; Chromosomal Instability/*genetics ; Epithelium/metabolism/*pathology ; Humans ; Pancreas/metabolism/*pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Telomere/genetics/*pathology ; *Telomere Shortening ; }, abstract = {A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, -2 and -3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and -2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer.}, } @article {pmid25651066, year = {2015}, author = {Davidovitch, M and Levit-Binnun, N and Golan, D and Manning-Courtney, P}, title = {Late diagnosis of autism spectrum disorder after initial negative assessment by a multidisciplinary team.}, journal = {Journal of developmental and behavioral pediatrics : JDBP}, volume = {36}, number = {4}, pages = {227-234}, doi = {10.1097/DBP.0000000000000133}, pmid = {25651066}, issn = {1536-7312}, mesh = {Age Factors ; Autism Spectrum Disorder/*diagnosis ; Child ; Cohort Studies ; *Delayed Diagnosis ; Female ; Humans ; Israel ; Male ; Patient Care Team ; }, abstract = {OBJECTIVE: Describe a cohort of children who received a diagnosis of autism spectrum disorder (ASD) after age 6 and after having undergone a comprehensive multidisciplinary assessment before the age of 6, through which they were not diagnosed with ASD.

METHODS: Extensive chart review of patients' electronic medical records comprised a representative population-based registry of patients seen during 2004 to 2011. The study focused only on the cohort of children who were diagnosed with ASD after the age of 6 but were not diagnosed with ASD at an earlier age. The charts were reviewed for the number of developmental assessments completed and the clinician's diagnostic impressions. The charts were also examined for documentation of ASD-suggestive features pulled directly from the text of the evaluators' reports.

RESULTS: A total of 221 patients (189 males) were diagnosed with ASD after age 6 although their initial comprehensive developmental evaluations before the age of 6 were negative for ASD. The study cohort underwent a total of 1028 developmental evaluations before the age of 6, with initial diagnostic impressions that included language deficits (70%), motor difficulties (67%), attention problems (46%), and cognitive difficulties (42%). Less than half of the cohort had ASD-suggesting features documented in their initial assessment.

CONCLUSIONS: Subsequent late diagnosis of ASD after an initial ASD-negative comprehensive assessment is a common clinical experience. Reasons for this scenario may include evolving diagnosis as well as missed and overdiagnosed cases of ASD.}, } @article {pmid25648466, year = {2015}, author = {Boland, MR and Prichard, RS and Daskalova, I and Lowery, AJ and Evoy, D and Geraghty, J and Rothwell, J and Quinn, CM and O'Doherty, A and McDermott, EW}, title = {Axillary nodal burden in primary breast cancer patients with positive pre-operative ultrasound guided fine needle aspiration cytology: management in the era of ACOSOG Z011.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {41}, number = {4}, pages = {559-565}, doi = {10.1016/j.ejso.2015.01.011}, pmid = {25648466}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Breast Neoplasms, Male/pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Image-Guided Biopsy ; *Lymph Node Excision ; Lymph Nodes/diagnostic imaging/*pathology/*surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Preoperative Care ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Tumor Burden ; Ultrasonography, Interventional ; Young Adult ; }, abstract = {INTRODUCTION: Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy (SLNB). Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology (AUS/FNAC) may represent a higher axillary disease burden mandating an axillary clearance and thus an upfront SLNB may be avoided. The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance (ALND) based on ACOSOG Z011 criteria.

METHODS: A retrospective review of a prospectively maintained database identified patients with positive pre-operative AUS/FNAC between 2007 and 2012. Core biopsies were excluded. Demographic and tumour characteristics were analysed. Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified.

RESULTS: 432 patients were identified with positive AUS/FNAC. 85 patients were excluded leaving 347 for analysis. Median age was 56 years (22-87), median tumour size was 25 mm (1.5 mm-150 mm) and median tumour pathology was grade 3 (50%) and invasive ductal carcinoma (82%). Median number of nodes removed at ALND was 23 (1-55) with a median number of positive nodes being 4 (1-47). 134 (39%) patients had ≤2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study. When other ACOSOG Z011 exclusion factors were applied only 27 (7.8%) patients may have avoided ALND.

CONCLUSIONS: Nodal positivity on AUS/FNAC is associated with higher axillary disease burden. Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary.}, } @article {pmid25645984, year = {2015}, author = {Cao, YW and Wan, GX and Sun, JP and Cui, XB and Hu, JM and Liang, WH and Zheng, YQ and Li, WQ and Li, F}, title = {Implications of the Notch1-Snail/Slug-epithelial to mesenchymal transition axis for lymph node metastasis in infiltrating ductal carcinoma.}, journal = {The Kaohsiung journal of medical sciences}, volume = {31}, number = {2}, pages = {70-76}, doi = {10.1016/j.kjms.2014.11.008}, pmid = {25645984}, issn = {2410-8650}, mesh = {Antigens, CD/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, Notch1/*metabolism ; Snail Family Transcription Factors ; Transcription Factors/*metabolism ; }, abstract = {Emerging evidence suggests that activation of the Notch1 signaling pathway inducing epithelial to mesenchymal transition (EMT) mediated by Snail/Slug promotes invasion and metastasis of breast cancer cells in vitro. However, the implication of the Notch1-Snail/Slug-EMT axis in breast cancer patients remains unclear. A total of 200 formalin-fixed paraffin-embedded samples of invasive ductal carcinoma (IDC), and 37 adjacent non-neoplastic tissue (ANNT) samples from patients who had not been treated with neoadjuvant therapy were examined. Expression of Notch1, Slug, Snail, E-cadherin, N-cadherin, and vimentin was determined by immunohistochemistry on tissue microarrays (TMAs). The correlation between protein expression and clinicopathological characteristics of breast cancer patients was also evaluated. Results showed that a significantly high percentage of cases with high expression of Notch1 (74%, 148/200), Slug (36%, 72/200), Snail (62%, 124/200), and N-cadherin (77%, 153/200) and a low percentage of cases with high expression of E-cadherin (27%, 54/200) were observed in IDC compared to those in ANNTs. High Notch1, Slug, Snail, and N-cadherin expression and low E-cadherin expression in patients with IDC were significantly correlated with lymph node metastasis. In addition, correlation analysis results revealed that high Notch1 expression was significantly associated with high Slug, Snail, and N-cadherin expression and low E-cadherin expression in IDC. Furthermore, a high Snail expression was significantly associated with low E-cadherin expression, and a high Slug expression was found to be significantly associated with increased N-cadherin expression in patients with IDC. Hence, our study suggested that the Notch1-Snail/Slug-EMT axis may be implicated in the lymph node metastasis affecting patients with IDC.}, } @article {pmid25644728, year = {2014}, author = {Moschetta, M and Telegrafo, M and Cornacchia, I and Vincenti, L and Ranieri, V and Cirili, A and Rella, L and Stabile Ianora, AA and Angelelli, G}, title = {PIP breast implants: rupture rate and correlation with breast cancer.}, journal = {Il Giornale di chirurgia}, volume = {35}, number = {11-12}, pages = {274-278}, pmid = {25644728}, issn = {0391-9005}, mesh = {Adult ; *Breast Implants ; Breast Neoplasms/*diagnosis/*epidemiology/etiology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Prospective Studies ; *Prosthesis Failure ; }, abstract = {AIM: To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma.

PATIENTS AND METHODS: 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years' experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture.

RESULTS: 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed.

CONCLUSION: The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated.}, } @article {pmid25640082, year = {2015}, author = {Li, L and Wang, K and Sun, X and Wang, K and Sun, Y and Zhang, G and Shen, B}, title = {Parameters of dynamic contrast-enhanced MRI as imaging markers for angiogenesis and proliferation in human breast cancer.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {21}, number = {}, pages = {376-382}, pmid = {25640082}, issn = {1643-3750}, mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Biomarkers/metabolism ; Breast Neoplasms/*diagnosis/metabolism/*pathology ; Cell Proliferation ; Contrast Media/*chemistry ; Endoglin ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neovascularization, Pathologic/*pathology ; Permeability ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Receptors, Cell Surface/metabolism ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy and the leading cause of cancer death in women worldwide; however, early diagnosis has been difficult due to its complex pathological structure. This study evaluated the value of morphological examination in conjunction with dynamic contrast-enhanced MRI (DCE-MRI) for more precise diagnosis of breast cancer, as well as their correlation with angiogenesis and proliferation biomarkers.

MATERIAL/METHODS: DCE-MRI parameters (including Ktrans: volume transfer coefficient reflecting vascular permeability, Kep: flux rate constant, Ve: extracellular volume ratio reflecting vascular permeability, and ADC: apparent diffusion coefficient) were obtained from 124 patients with breast cancer (124 lesions). Microvessel density (MVD) was evaluated by the immunohistochemical analysis of tumor vessels for CD31 and CD105 expression. The proliferation was assessed by analyzing Ki67.

RESULTS: Ktrans values were in the order of: malignant lesions>benign lesions>normal glands. Similar results were observed for Kep. The opposite changes were seen with Ve. Ktrans and Kep values were significantly higher in invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) than in mammary ductal dysplasia (MDD; ANOVA followed by Dunnett's test). In sharp contrast, ADC values were lower in IDC and DCIS than in MDD, and Ve was not significantly different among the three groups. The data from MIP (maximum intensity projection) showed that benign breast lesions had no or only one blood vessel, whereas malignant lesions had two or more blood vessels. In addition, expression of CD105 and Ki67, the commonly recognized markers for angiogenesis and proliferation, respectively, were closely correlated with MRI parameters as revealed by Pearson analysis.

CONCLUSIONS: Determination of Ktrans, Kep and ADC values permits estimation of tumor angiogenesis and proliferation in breast cancer and DCE-MRI parameters can be used as imaging biomarkers to predict patient prognosis and the biologic aggressiveness of the tumor.}, } @article {pmid25638396, year = {2015}, author = {Shin, S and Ko, ES and Kim, RB and Han, BK and Nam, SJ and Shin, JH and Hahn, SY}, title = {Effect of menstrual cycle and menopausal status on apparent diffusion coefficient values and detectability of invasive ductal carcinoma on diffusion-weighted MRI.}, journal = {Breast cancer research and treatment}, volume = {149}, number = {3}, pages = {751-759}, doi = {10.1007/s10549-015-3278-6}, pmid = {25638396}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology/physiopathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/physiopathology ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Menopause/physiology ; Menstrual Cycle/*physiology ; Middle Aged ; Radiography ; }, abstract = {The purpose of this study was to determine whether the apparent diffusion coefficient (ADC) and tumor detectability based on diffusion-weighted imaging (DWI) are affected by the menstrual cycle or menopausal status in breast cancer patients. Institutional review board approval was obtained, and the requirement for informed consent was waived. A total of 124 women with invasive ductal carcinoma not otherwise specified (IDC NOS) who underwent breast MRI with DWI were included in this study. Two radiologists retrospectively measured the ADCs of tumor and contralateral normal glandular tissue and scored the tumor detectability. The ADCs and detectability were compared to menstrual cycle and menopausal status, based on patient questionnaires. ADCs of tumors and contralateral tissue were significantly lower in postmenopausal women than in premenopausal women (P = 0.006 and P < 0.001, respectively). Tumor detectability did not differ significantly between the premenopausal and postmenopausal groups (P = 0.454). Normalized ADCs were not significantly lower in postmenopausal women compared to premenopausal women (P = 0.880). There was no statistically significant difference in the absolute, contralateral, and normalized ADCs (P = 0.091, 0.809, and 0.299, respectively), and the tumor detectability (P = 0.680) according to the menstrual cycle. Although ADCs of the IDC and normal glandular tissue in postmenopausal women were significantly lower than those in premenopausal women, the menstrual cycle did not affect tumor detectability and ADCs of IDC.}, } @article {pmid25632310, year = {2015}, author = {Timoteo, AR and Albuquerque, BM and Moura, PC and Ramos, CC and Agnez-Lima, LF and Walsh, T and King, MC and Lajus, TB}, title = {Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer.}, journal = {Hereditary cancer in clinical practice}, volume = {13}, number = {1}, pages = {2}, pmid = {25632310}, issn = {1731-2302}, support = {R01 CA175716/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer.

METHODS AND RESULTS: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496.

CONCLUSION: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.}, } @article {pmid25628648, year = {2014}, author = {Lau, AC and Csankovszki, G}, title = {Condensin-mediated chromosome organization and gene regulation.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {473}, pmid = {25628648}, issn = {1664-8021}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; }, abstract = {In many organisms sexual fate is determined by a chromosome-based method which entails a difference in sex chromosome-linked gene dosage. Consequently, a gene regulatory mechanism called dosage compensation equalizes X-linked gene expression between the sexes. Dosage compensation initiates as cells transition from pluripotency to differentiation. In Caenorhabditis elegans, dosage compensation is achieved by the dosage compensation complex (DCC) binding to both X chromosomes in hermaphrodites to downregulate gene expression by twofold. The DCC contains a subcomplex (condensin I(DC)) similar to the evolutionarily conserved condensin complexes which play a fundamental role in chromosome dynamics during mitosis. Therefore, mechanisms related to mitotic chromosome condensation are hypothesized to mediate dosage compensation. Consistent with this hypothesis, monomethylation of histone H4 lysine 20 is increased, whereas acetylation of histone H4 lysine 16 is decreased, both on mitotic chromosomes and on interphase dosage compensated X chromosomes in worms. These observations suggest that interphase dosage compensated X chromosomes maintain some characteristics associated with condensed mitotic chromosome. This chromosome state is stably propagated from one cell generation to the next. In this review we will speculate on how the biochemical activities of condensin can achieve both mitotic chromosome compaction and gene repression.}, } @article {pmid25625899, year = {2015}, author = {Burke, KA and Dawes, RP and Cheema, MK and Van Hove, A and Benoit, DS and Perry, SW and Brown, E}, title = {Second-harmonic generation scattering directionality predicts tumor cell motility in collagen gels.}, journal = {Journal of biomedical optics}, volume = {20}, number = {5}, pages = {051024}, pmid = {25625899}, issn = {1560-2281}, support = {F31 CA183351/CA/NCI NIH HHS/United States ; 5T32NS007489-13/NS/NINDS NIH HHS/United States ; R21 CA185216/CA/NCI NIH HHS/United States ; R01 AR064200/AR/NIAMS NIH HHS/United States ; DP2 OD006501/OD/NIH HHS/United States ; R01AR064200/AR/NIAMS NIH HHS/United States ; R21DA030256/DA/NIDA NIH HHS/United States ; F31CA183351/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32AI007285/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Collagen/*chemistry ; Disease Progression ; Female ; Gels/chemistry ; Image Processing, Computer-Assisted ; Mice ; Mice, Inbred BALB C ; Microscopy, Fluorescence, Multiphoton/*instrumentation/*methods ; Neoplasm Metastasis ; Signal Transduction ; }, abstract = {Second-harmonic generation (SHG) allows for the analysis of tumor collagen structural changes throughout metastatic progression. SHG directionality, measured through the ratio of the forward-propagating to backward-propagating signal (F/B ratio), is affected by collagen fibril diameter, spacing, and disorder of fibril packing within a fiber. As tumors progress, these parameters evolve, producing concurrent changes in F/B. It has been recently shown that the F/B of highly metastatic invasive ductal carcinoma (IDC) breast tumors is significantly different from less metastatic tumors. This suggests a possible relationship between the microstructure of collagen, as measured by the F/B, and the ability of tumor cells to locomote through that collagen. Utilizing in vitro collagen gels of different F/B ratios, we explored the relationship between collagen microstructure and motility of tumor cells in a “clean” environment, free of the myriad cells, and signals found in in vivo. We found a significant relationship between F/B and the total distance traveled by the tumor cell, as well as both the average and maximum velocities of the cells. Consequently, one possible mechanism underlying the observed relationship between tumor F/B and metastatic output in IDC patient samples is a direct influence of collagen structure on tumor cell motility.}, } @article {pmid25620480, year = {2014}, author = {Hua, X and Huang, X and Liao, Z and Xian, Q and Yu, L}, title = {[Changes of fibroblast immunophenotype and their clinical significance in stromal remodeling of breast tumors].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {36}, number = {11}, pages = {834-838}, pmid = {25620480}, issn = {0253-3766}, mesh = {Breast ; Breast Neoplasms/immunology/*pathology ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Endopeptidases ; Fibroblasts/*immunology ; Gelatinases/metabolism ; Humans ; Hyperplasia ; Immunohistochemistry ; Immunophenotyping ; Membrane Proteins/metabolism ; Serine Endopeptidases/metabolism ; }, abstract = {OBJECTIVE: To evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling.

METHODS: CD34, FAP-α, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC).

RESULTS: The positive expression rates of CD34, FAP-α and α-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, α-SMA and FAP-α in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (χ(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)α-SMA(+)FAP-α(+). There were statistically significant differences in the expression of CD34, α-SMA and FAP-α between IDC and ADH, DCIS and normal breast tissues (χ(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) α-SMA(+) FAP-α(+).

CONCLUSIONS: Immunophenotype conversion from CD34(+) α-SMA(-) FAP-α(-) to CD34(-) α-SMA(+)FAP-α(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.}, } @article {pmid25618286, year = {2014}, author = {Nakash, O and Nagar, M and Levav, I}, title = {Presenting problems and treatment expectations among service users accessing psychiatric outpatient care: are there gender differences?.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {51}, number = {3}, pages = {212-217}, pmid = {25618286}, issn = {2617-2402}, mesh = {Adult ; Ambulatory Care/*statistics & numerical data ; Female ; Humans ; Israel ; Male ; Mental Health Services/*statistics & numerical data ; Patient Acceptance of Health Care/*statistics & numerical data ; Sex Factors ; }, abstract = {BACKGROUND: Community-based studies have documented gender differences in mental health problems and service utilization. This mixed methods study explored gender differences in severity of emotional distress, referral paths, presenting problems and care expectations among service users upon accessing outpatient psychiatric care.

METHODS: Consecutive service users (N=284, 64% women) who presented for a new or repeated episode of care in adult outpatient clinics completed questionnaires on a measure of emotional distress, treatment history and referral path. These variables were quantitatively analyzed. Also, users completed two open-ended questionnaires on reasons for seeking care and expectations from the services. These variables were qualitatively analyzed using thematic analyses.

RESULTS: No significant gender differences emerged on any of the variables examined among new and repeated users. The main reasons for seeking care were psychiatric symptoms as well as non-specific psychopathology. The most frequent expectations from the services were receiving psychotherapy and specific tools to better manage life problems.

LIMITATIONS: The sample of new male service users was relatively small.

CONCLUSIONS: Once care is initiated, men and women showed similar clinical presentation and care expectations.}, } @article {pmid25616712, year = {2015}, author = {Wu, Y and Fu, F and Lian, Y and Chen, J and Wang, C and Nie, Y and Zheng, L and Zhuo, S}, title = {Monitoring morphological alterations during invasive ductal breast carcinoma progression using multiphoton microscopy.}, journal = {Lasers in medical science}, volume = {30}, number = {3}, pages = {1109-1115}, pmid = {25616712}, issn = {1435-604X}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/diagnosis/metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnosis/metabolism/*pathology ; Collagen/metabolism ; Disease Progression ; Female ; Humans ; Microscopy, Fluorescence, Multiphoton ; Middle Aged ; Neoplasm Staging ; }, abstract = {Morphological alteration of cells and matrices is critical for tumor initiation and progression. Monitoring these alterations during tumor progression is vitally important for making real-time histological diagnoses of tumor staging. In this study, 20 pairs of normal and cancerous human breast tissues were imaged by multiphoton microscopy (MPM), and nuclear area and collagen density were quantified by LSM 5 software (version 3.2). Comparison of MPM images from normal breast tissue with low- and high-grade invasive ductal carcinoma (IDC) lesions clearly showed changes in both cellular features and extracellular matrix architecture during IDC development. Moreover, analysis of nuclear area and collagen density established a quantitative link between these two morphological features and progression of IDC. Present results demonstrated that MPM can provide both qualitative and quantitative evaluations of tumor progression. With additional development, this technique has the potential to make real-time histological diagnoses of tumor staging and guide development of efficacious clinical therapies.}, } @article {pmid25615557, year = {2015}, author = {Surmacki, J and Brozek-Pluska, B and Kordek, R and Abramczyk, H}, title = {The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.}, journal = {The Analyst}, volume = {140}, number = {7}, pages = {2121-2133}, doi = {10.1039/c4an01876a}, pmid = {25615557}, issn = {1364-5528}, mesh = {Breast Neoplasms/chemistry/*pathology ; *Carcinogenesis ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Carcinoma, Lobular/chemistry/*pathology ; Discriminant Analysis ; Humans ; Least-Squares Analysis ; Optical Imaging ; *Phenotype ; Principal Component Analysis ; Reactive Oxygen Species/*chemistry ; *Spectrum Analysis, Raman ; }, abstract = {Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.}, } @article {pmid25613435, year = {2015}, author = {Kemp, TL and Kilgore, MR and Javid, SH}, title = {Invasive ductal carcinoma arising within a large mammary hamartoma.}, journal = {The breast journal}, volume = {21}, number = {2}, pages = {196-197}, doi = {10.1111/tbj.12378}, pmid = {25613435}, issn = {1524-4741}, mesh = {Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Female ; Hamartoma/*diagnosis ; Humans ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Ultrasonography, Mammary ; }, } @article {pmid25604797, year = {2015}, author = {Braunstein, LZ and Brock, JE and Chen, YH and Truong, L and Russo, AL and Arvold, ND and Harris, JR}, title = {Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin.}, journal = {Breast cancer research and treatment}, volume = {149}, number = {2}, pages = {555-564}, doi = {10.1007/s10549-015-3273-y}, pmid = {25604797}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Lobular/*pathology/radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retreatment ; Risk Factors ; Time Factors ; Tumor Burden ; Young Adult ; }, abstract = {Invasive lobular carcinoma (ILC) typically presents at a later stage than invasive ductal carcinoma (IDC) and poses unique radiographic and surgical challenges. However, current principles of breast-conserving therapy (BCT) do not distinguish between histologic subtypes, raising uncertainty about the optimal approach for patients with ILC. We studied 998 BCT patients from 1998-2007, comprised 74 % IDC, 8 % ILC, and 18 % with mixed ILC/IDC. In light of recent guidelines addressing surgical margins, specimens were assessed for margin width and biologic subtype. The Kaplan-Meier method and Cox proportional hazards models were used to analyze effects of patient and disease characteristics on local recurrence (LR). At a median of 119 months, 45 patients had an isolated LR. 10-year LR was 5.5 % for patients with IDC, 4.4 % for ILC, and 1.2 % for mixed histology (p = 0.08). The majority of ILC cases had luminal A biologic subtype (91.1 %), and analysis among all luminal A cases revealed 10-year LR of 2.6 % for IDC, 3.4 % for ILC, and 0 % for mixed tumors (p = 0.12). Patients with ILC were more likely to have initially positive surgical margins (45.0 vs 17.5 %; p < 0.001) resulting in more frequent re-excision (57.1 % vs 40.4 %; p = 0.02), though final margins were similar between ILC and IDC (p = 0.88). No LR was observed among ILC or mixed histology patients with margins <2 mm (n = 28). On multivariate analysis, histologic subtype was not associated with LR (p = 0.52). Modern approaches confer similarly favorable LR rates for ILC, IDC, and mixed histology breast cancers despite inherent histologic differences. Patients with ILC did not require more extensive surgical margins than those with IDC.}, } @article {pmid25600504, year = {2015}, author = {Orucevic, A and Chen, J and McLoughlin, JM and Heidel, RE and Panella, T and Bell, J}, title = {Is the TNM staging system for breast cancer still relevant in the era of biomarkers and emerging personalized medicine for breast cancer - an institution's 10-year experience.}, journal = {The breast journal}, volume = {21}, number = {2}, pages = {147-154}, doi = {10.1111/tbj.12367}, pmid = {25600504}, issn = {1524-4741}, mesh = {Biomarkers, Tumor/*blood ; Breast Neoplasms/blood/classification/*pathology ; Carcinoma, Ductal, Breast/blood/classification/*pathology ; Female ; Humans ; Neoplasm Staging ; Precision Medicine/methods ; Prospective Studies ; Receptor, ErbB-2/blood ; Receptors, Estrogen/blood ; Receptors, Progesterone/blood ; }, abstract = {We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000-2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five-group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty-two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non-TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01-1.97; Stage III = HR 3.96, 95% CI 2.68-5.88; Stage IV = HR 27.25, 95% CI 16.84-44.08), and age (HR 1.05, 95% CI 1.04-1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88-5.04, Stage IV = HR 24.36, 95% CI 13.81-42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).}, } @article {pmid25598762, year = {2014}, author = {Shakoor, MT and Ayub, S and Mohindra, R and Ayub, Z and Ahad, A}, title = {Unique presentations of invasive lobular breast cancer: a case series.}, journal = {International journal of biomedical science : IJBS}, volume = {10}, number = {4}, pages = {287-293}, pmid = {25598762}, issn = {1550-9702}, abstract = {INTRODUCTION: Breast carcinoma is the most common malignancy in women. Unlike IDC, which typically metastasizes to the lung, liver or bone, ILC has been found to metastasize to GI tract, peritoneum and retroperitoneum. Nonspecific symptomology may be considered secondary to other diseases and this can delay the definite diagnosis and treatment of metastatic disease. Knowledge of the pattern of disease spread is essential for accurate diagnosis and early initiation of systemic treatment, thus avoiding unnecessary interventions. We are reporting three unique cases of metastatic ILC presenting with wide range of symptoms.

CASE PRESENTATIONS: Case A: 69-year-old female presented with recurrent jaundice. Case B: 77-year-old female with the past medical history of right breast ILC seven years ago status post right radical mastectomy with chemotherapy, presented with anemia. Case C: 56-year-old female presented with bright red blood per rectum.

CONCLUSION: A high level of suspicion is needed for metastatic breast cancer in patients with history of ILC, regardless of disease free interval. Since it frequently metastasizes to unusual sites and presents with a wide spectrum of symptoms.}, } @article {pmid25598690, year = {2015}, author = {Choi, JW and Moon, WJ and Choi, N and Roh, HG and Kim, MY and Kim, NR and Moon, SG and Chung, HW and Lim, SD and Yang, JH}, title = {Charcoal-induced granuloma that mimicked a nodal metastasis on ultrasonography and FDG-PET/CT after neck dissection.}, journal = {Korean journal of radiology}, volume = {16}, number = {1}, pages = {196-200}, pmid = {25598690}, issn = {2005-8330}, mesh = {Breast Neoplasms/pathology/surgery/therapy ; Carcinoma/*pathology/surgery/therapy ; Cervix Uteri/diagnostic imaging/pathology ; Charcoal/toxicity ; Female ; Fluorodeoxyglucose F18 ; Granuloma/*diagnosis/pathology ; Humans ; Lymph Nodes/diagnostic imaging/*surgery ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Radiopharmaceuticals ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Charcoal can be used for preoperative localization of metastatic lymph nodes in the neck. Charcoal remains stable without causing foreign body reactions during as hort period. However, foreign body reactions may develop if charcoal is left in situ for more than 6 months. We reported a case of charcoal granuloma mimicking local recurrence on fluorodeoxyglucose-positron emission tomography/computed tomography and ultrasonography in a 47-year-old woman who had cervical lymph node dissection due to metastatic invasive ductal carcinoma of the breast.}, } @article {pmid25591838, year = {2015}, author = {Ogunbiyi, SO and Lee, S and Mathew, J and Cheung, KL}, title = {Primary breast cancer in the elderly: a systematic literature review on histological type and clinical outcome.}, journal = {Future oncology (London, England)}, volume = {11}, number = {2}, pages = {259-265}, doi = {10.2217/fon.14.210}, pmid = {25591838}, issn = {1744-8301}, mesh = {Age Factors ; Breast Neoplasms/mortality/*therapy ; Carcinoma, Ductal, Breast/mortality/*therapy ; Disease-Free Survival ; Female ; Humans ; Treatment Outcome ; }, abstract = {The objective was to determine whether histological types of breast cancer in elderly women influence clinical outcome. Four major databases were searched. All relevant articles, from January 1990 to December 2013, were screened. After applying inclusion and exclusion criteria, 11 studies were included. Invasive ductal carcinoma was the commonest (68.5-87.1%) histological type, followed by lobular carcinoma (6.9-17.7%). Four studies reported on survival. However, none specifically looked at survival according to different histological types. There are very little data on the influence of histological type on clinical outcome in primary breast cancer in elderly patients. Further studies may elucidate any potential influence and its relationship with tumor biology.}, } @article {pmid25591592, year = {2015}, author = {Lehotska, V and Rauova, K and Vanovcanova, L}, title = {MR-mammography - impact on disease extent determination and surgical treatment of invasive ductal and lobular breast cancers.}, journal = {Neoplasma}, volume = {62}, number = {2}, pages = {269-277}, doi = {10.4149/neo_2015_032}, pmid = {25591592}, issn = {0028-2685}, abstract = {UNLABELLED: The aim of this study is to assess the impact of multiparametric MR imaging to an exact determination of the extent of invasive ductal and lobular breast cancers in routine clinical practice.180 women aged 27-74 years (median 52.4 years) with newly diagnosed invasive ductal and lobular breast cancers confirmed by core-cut or vacuum-assisted biopsy were examined by all three imaging modalities, i.e. digital X-ray mammography, ultrasonography and 3T MR-mammography. In case of MR-mammography an extended protocol, i.e. combination of morphological breast MRI + DCE + DWI was used. For overall detection and determination of the extent of invasive breast cancers (IDC + ILC) MRmammography alone reached the diagnostic accuracy of 72.48%, while X-ray mammography 69.12% and ultrasonography 59.87%. In cases of ILC combination of X-ray mammography and MR- mammography with sensitivity of 96.15% was the most effective. In comparison with X-ray mammography and ultrasonography MR-mammography had higher sensitivity (96.15%, versus 90.28%) in the diagnosis of multifocal/ multicentric invasive lobular carcinoma and invasive ductal carcinoma with extensive intraductal component, as well. 3T MR-mammography is an effective complementary consulting modality to digital X-ray mammography and ultrasonography, and it is particularly beneficial in the detection of additional mammographically and ultrasonografically occult breast lesions, as well as in the determination of the real extent of pathological changes in the ipsilateral and contralateral breast.

KEYWORDS: MR-mammography, occult breast cancer, invasive ductal cancer, invasive lobular cancer, multifocality, multicentricity.}, } @article {pmid25588857, year = {2015}, author = {McNamara, KM and Yoda, T and Miki, Y and Nakamura, Y and Suzuki, T and Nemoto, N and Miyashita, M and Nishimura, R and Arima, N and Tamaki, K and Ishida, T and Ohuchi, N and Sasano, H}, title = {Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer.}, journal = {The International journal of biological markers}, volume = {30}, number = {2}, pages = {e184-9}, doi = {10.5301/jbm.5000132}, pmid = {25588857}, issn = {1724-6008}, mesh = {Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Receptors, Androgen/*metabolism ; Triple Negative Breast Neoplasms/*blood/pathology ; }, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse subgroup, but one promising marker and therapeutic target of this breast cancer is the androgen receptor (AR). Previously we demonstrated that AR and cognate intracrine pathways are associated with decreased proliferation in invasive ductal carcinoma with their decrease also detected between organ-confined and invasive diseases. Therefore, in this study, we examined the status of AR and androgen-producing enzymes during the process of metastasis to lymph nodes and cancer recurrence.

MATERIALS AND METHODS: We studied 2 series of patients with TNBC, one from Kumamoto University Hospital composed of 16 matched cases of primary and locally or distal recurrences and the other from Tohoku University Hospital examining 46 lymph node metastasis from 23 patients. In addition to studying concordance in AR expression, we also examined the interactions between AR and Ki-67 labeling index and AR and site of distal metastasis.

RESULTS: In both series, AR status was concordant between primary and recurrent/metastatic disease, but coordinated expression of AR and androgenic enzymes was lost during the process. The inverse association between AR and Ki-67, previously reported in invasive ductal carcinoma (IDC), was markedly potentiated in both lymph node and recurrent cancers. In addition, AR expression appeared to have little effect on visceral metastasis but was associated directly with bone metastasis and inversely with brain metastasis.

CONCLUSIONS: The results of our present study demonstrated that AR remained in the majority of metastatic samples from AR-positive primary TNBCs and that AR manipulation could be exploited in the metastatic settings of TNBC.}, } @article {pmid25587452, year = {2014}, author = {Barros, AC and Hanna, SA and Carvalho, HA and Martella, E and Andrade, FE and Piato, JR and Bevilacqua, JL}, title = {Intraoperative full-dose of partial breast irradiation with electrons delivered by standard linear accelerators for early breast cancer.}, journal = {International journal of breast cancer}, volume = {2014}, number = {}, pages = {568136}, pmid = {25587452}, issn = {2090-3170}, abstract = {Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma (T ≤ 3.0 cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40-85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC.}, } @article {pmid25585858, year = {2015}, author = {Bas, R and Vallverdú, M and Valencia, JF and Voss, A and de Luna, AB and Caminal, P}, title = {Evaluation of acceleration and deceleration cardiac processes using phase-rectified signal averaging in healthy and idiopathic dilated cardiomyopathy subjects.}, journal = {Medical engineering & physics}, volume = {37}, number = {2}, pages = {195-202}, doi = {10.1016/j.medengphy.2014.12.001}, pmid = {25585858}, issn = {1873-4030}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/diagnosis/*physiopathology ; Case-Control Studies ; Death, Sudden, Cardiac ; *Deceleration ; Feasibility Studies ; Female ; Follow-Up Studies ; Heart/*physiology/*physiopathology ; Humans ; Male ; Middle Aged ; Risk Assessment ; *Signal Processing, Computer-Assisted ; Sleep ; Wakefulness ; }, abstract = {The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients.}, } @article {pmid25585381, year = {2015}, author = {Yang, M and Tang, M and Ma, X and Yang, L and He, J and Peng, X and Guo, G and Zhou, L and Luo, N and Yuan, Z and Tong, A}, title = {AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.}, journal = {Biochemical and biophysical research communications}, volume = {457}, number = {3}, pages = {347-352}, doi = {10.1016/j.bbrc.2014.12.115}, pmid = {25585381}, issn = {1090-2104}, mesh = {Amino Acid Sequence ; Antimicrobial Cationic Peptides/chemistry/*genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/genetics/metabolism/pathology ; Conserved Sequence ; DNA, Neoplasm/metabolism ; DNA-Binding Proteins/chemistry/*genetics/*metabolism ; Humans ; Molecular Sequence Data ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Tissue Distribution ; Tumor Suppressor Proteins/chemistry/genetics/metabolism ; }, abstract = {Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.}, } @article {pmid25583208, year = {2015}, author = {Bursle, EC and Dyer, J and Looke, DF and McDougall, DA and Paterson, DL and Playford, EG}, title = {Risk factors for urinary catheter associated bloodstream infection.}, journal = {The Journal of infection}, volume = {70}, number = {6}, pages = {585-591}, doi = {10.1016/j.jinf.2015.01.001}, pmid = {25583208}, issn = {1532-2742}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Australia/epidemiology ; Bacteremia ; Case-Control Studies ; Catheter-Related Infections/drug therapy/*epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Urinary Catheterization/*adverse effects ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/drug therapy/*epidemiology ; }, abstract = {OBJECTIVES: Urinary catheter associated bloodstream infection (UCABSI) causes significant morbidity, mortality and healthcare costs. We aimed to define the risk factors for UCABSI.

METHODS: A case-control study was conducted at two Australian tertiary hospitals. Patients with urinary source bloodstream infection associated with an indwelling urinary catheter (IDC) were compared to controls with an IDC who did not develop urinary source bloodstream infection.

RESULTS: There were 491 controls and 67 cases included in the analysis. Independent statistically significant risk factors for the development of UCABSI included insertion of the catheter in operating theatre, chronic kidney disease, age-adjusted Charlson comorbidity index, accurate urinary measurements as reason for IDC insertion and dementia. IDCs were inserted for valid reasons in nearly all patients, however an appropriate indication at 48 h post-insertion was found in only 44% of patients. Initial empiric antibiotics were deemed inappropriate in 23 patients (34%).

CONCLUSION: To our knowledge, this is the first study to look specifically at the risk factors for bloodstream infection in urinary catheterised patients. Several risk factors were identified. IDC management and empiric management of UCABSI could be improved and is likely to result in a decreased incidence of infection and its complications.}, } @article {pmid25579460, year = {2015}, author = {Weinfurtner, RJ and Patel, B and Laronga, C and Lee, MC and Falcon, SL and Mooney, BP and Yue, B and Drukteinis, JS}, title = {Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics.}, journal = {Clinical breast cancer}, volume = {15}, number = {3}, pages = {234-239}, doi = {10.1016/j.clbc.2014.12.005}, pmid = {25579460}, issn = {1938-0666}, mesh = {Aged ; Biopsy, Large-Core Needle/*methods ; Breast/*pathology ; Breast Neoplasms/*pathology ; Female ; Humans ; Hyperplasia/*pathology ; Image-Guided Biopsy ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {UNLABELLED: Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk histopathologic features at a single institution found an overall upstage rate to malignancy of 14% at surgical excision. All upstaged lesions were associated with atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular hyperplasia alone or with lobular carcinoma in situ were not associated with an upstage to malignancy.

INTRODUCTION: The purpose of the present study w as to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS).

MATERIALS AND METHODS: A retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed.

RESULTS: A total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis.

CONCLUSION: MRI-guided breast biopsies yielding high-risk histopathologic features were associated with an overall upstage to malignancy rate of 14% at surgical excision. All upstaged lesions were associated with ADH. FEA and ALH alone or with LCIS were not associated with an upstage to malignancy.}, } @article {pmid25574147, year = {2014}, author = {Yano, H and Nakayama, N and Morimitsu, K and Futamura, M and Ohe, N and Miwa, K and Shinoda, J and Iwama, T}, title = {Changes in protein level in the cerebrospinal fluid of a patient with cerebral radiation necrosis treated with bevacizumab.}, journal = {Clinical Medicine Insights. Oncology}, volume = {8}, number = {}, pages = {153-157}, pmid = {25574147}, issn = {1179-5549}, abstract = {A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus.}, } @article {pmid25573962, year = {2015}, author = {Scully, OJ and Yu, Y and Salim, A and Thike, AA and Yip, GW and Baeg, GH and Tan, PH and Matsumoto, K and Bay, BH}, title = {Complement component 1, q subcomponent binding protein is a marker for proliferation in breast cancer.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {240}, number = {7}, pages = {846-853}, pmid = {25573962}, issn = {1535-3699}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Blotting, Western ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carrier Proteins/analysis/*biosynthesis ; Cell Proliferation ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mitochondrial Proteins/analysis/*biosynthesis ; Protein Binding ; Real-Time Polymerase Chain Reaction ; Tissue Array Analysis ; Young Adult ; }, abstract = {Complement component 1, q subcomponent binding protein (C1QBP), is a multi-compartmental protein with higher mRNA expression reported in breast cancer tissues. This study evaluated the association between immunohistochemical expression of the C1QBP protein in breast cancer tissue microarrays (TMAs) and clinicopathological parameters, in particular tumor size. In addition, an in vitro study was conducted to substantiate the breast cancer TMA findings. Breast cancer TMAs were constructed from pathological specimens of patients diagnosed with invasive ductal carcinoma. C1QBP protein and proliferating cell nuclear antigen (PCNA) immunohistochemical analyses were subsequently performed in the TMAs. C1QBP immunostaining was detected in 131 out of 132 samples examined. The C1QBP protein was predominantly localized in the cytoplasm of the breast cancer cells. Univariate analysis revealed that a higher C1QBP protein expression was significantly associated with older patients (P = 0.001) and increased tumor size (P = 0.002). Multivariate analysis showed that C1QBP is an independent predictor of tumor size in progesterone-positive tumors. Furthermore, C1QBP was also significantly correlated with expression of PCNA, a known marker of proliferation. Inhibition of C1QBP expression was performed by transfecting C1QBP siRNA into T47D breast cancer cells, a progesterone receptor-positive breast cancer cell line. C1QBP gene expression was analyzed by real-time RT-PCR, and protein expression by Western blot. Cell proliferation assays were also performed by commercially available assays. Down-regulation of C1QBP expression significantly decreased cell proliferation and growth in T47D cells. Taken together, our findings suggest that the C1QBP protein could be a potential proliferative marker in breast cancer.}, } @article {pmid25571972, year = {2015}, author = {Vogel, S and Börger, V and Peters, C and Förster, M and Liebfried, P and Metzger, K and Meisel, R and Däubener, W and Trapp, T and Fischer, JC and Gawaz, M and Sorg, RV}, title = {Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death.}, journal = {Cell death and differentiation}, volume = {22}, number = {7}, pages = {1219-1230}, pmid = {25571972}, issn = {1476-5403}, mesh = {Animals ; *Apoptosis ; Chemotaxis ; Dendritic Cells/*physiology ; HMGB1 Protein/*metabolism ; Hepatocyte Growth Factor/*metabolism ; Humans ; Inflammation ; Male ; Mesenchymal Stem Cells/*physiology ; Mice ; Monocytes/*physiology ; Myocytes, Cardiac/metabolism/physiology ; *Necrosis ; Neurons/metabolism/physiology ; Regeneration ; }, abstract = {Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.}, } @article {pmid25566297, year = {2014}, author = {Roriz, M and Carvalho, SM and Vasconcelos, MW}, title = {High relative air humidity influences mineral accumulation and growth in iron deficient soybean plants.}, journal = {Frontiers in plant science}, volume = {5}, number = {}, pages = {726}, pmid = {25566297}, issn = {1664-462X}, abstract = {Iron (Fe) deficiency chlorosis (IDC) in soybean results in severe yield losses. Cultivar selection is the most commonly used strategy to avoid IDC but there is a clear interaction between genotype and the environment; therefore, the search for quick and reliable tools to control this nutrient deficiency is essential. Several studies showed that relative humidity (RH) may influence the long distance transport of mineral elements and the nutrient status of plants. Thus, we decided to analyze the response of an "Fe-efficient" (EF) and an "Fe-inefficient" (INF) soybean accession grown under Fe-sufficient and deficient conditions under low (60%) and high (90%) RH, evaluating morphological, and physiological parameters. Furthermore, the mineral content of different plant organs was analyzed. Our results showed beneficial effects of high RH in alleviating IDC symptoms as seen by increased SPAD values, higher plant dry weight (DW), increased plant height, root length, and leaf area. This positive effect of RH in reducing IDC symptoms was more pronounced in the EF accession. Also, Fe content in the different plant organs of the EF accession grown under deficient conditions increased with RH. The lower partitioning of Fe to roots and stems of the EF accessions relative to dry matter also supported our hypothesis, suggesting a greater capacity of this accession in Fe translocation to the aerial parts under Fe deficient conditions, when grown under high RH.}, } @article {pmid25565221, year = {2014}, author = {Plancoulaine, B and Laurinaviciene, A and Meskauskas, R and Baltrusaityte, I and Besusparis, J and Herlin, P and Laurinavicius, A}, title = {Digital immunohistochemistry wizard: image analysis-assisted stereology tool to produce reference data set for calibration and quality control.}, journal = {Diagnostic pathology}, volume = {9 Suppl 1}, number = {Suppl 1}, pages = {S8}, pmid = {25565221}, issn = {1746-1596}, mesh = {Algorithms ; Breast Neoplasms/*pathology ; Calibration ; Female ; Humans ; Image Processing, Computer-Assisted/standards ; Immunohistochemistry/standards ; Ki-67 Antigen/*analysis ; Linear Models ; Quality Control ; Reproducibility of Results ; }, abstract = {BACKGROUND: Digital image analysis (DIA) enables better reproducibility of immunohistochemistry (IHC) studies. Nevertheless, accuracy of the DIA methods needs to be ensured, demanding production of reference data sets. We have reported on methodology to calibrate DIA for Ki67 IHC in breast cancer tissue based on reference data obtained by stereology grid count. To produce the reference data more efficiently, we propose digital IHC wizard generating initial cell marks to be verified by experts.

METHODS: Digital images of proliferation marker Ki67 IHC from 158 patients (one tissue microarray spot per patient) with an invasive ductal carcinoma of the breast were used. Manual data (mD) were obtained by marking Ki67-positive and negative tumour cells, using a stereological method for 2D object enumeration. DIA was used as an initial step in stereology grid count to generate the digital data (dD) marks by Aperio Genie and Nuclear algorithms. The dD were collected into XML files from the DIA markup images and overlaid on the original spots along with the stereology grid. The expert correction of the dD marks resulted in corrected data (cD). The percentages of Ki67 positive tumour cells per spot in the mD, dD, and cD sets were compared by single linear regression analysis. Efficiency of cD production was estimated based on manual editing effort.

RESULTS: The percentage of Ki67-positive tumor cells was in very good agreement in the mD, dD, and cD sets: regression of cD from dD (R2=0.92) reflects the impact of the expert editing the dD as well as accuracy of the DIA used; regression of the cD from the mD (R2=0.94) represents the consistency of the DIA-assisted ground truth (cD) with the manual procedure. Nevertheless, the accuracy of detection of individual tumour cells was much lower: in average, 18 and 219 marks per spot were edited due to the Genie and Nuclear algorithm errors, respectively. The DIA-assisted cD production in our experiment saved approximately 2/3 of manual marking.

CONCLUSIONS: Digital IHC wizard enabled DIA-assisted stereology to produce reference data in a consistent and efficient way. It can provide quality control measure for appraising accuracy of the DIA steps.}, } @article {pmid25561121, year = {2014}, author = {Sierra Poyatos, R and Riobó Serván, P and Vázquez Martínez, C}, title = {[Effects of exenatide lar in type 2 diabetes mellitus and obesity].}, journal = {Nutricion hospitalaria}, volume = {31}, number = {1}, pages = {292-298}, doi = {10.3305/nh.2015.31.1.8283}, pmid = {25561121}, issn = {1699-5198}, mesh = {Aged ; Blood Glucose/analysis ; Body Mass Index ; Delayed-Action Preparations ; Diabetes Mellitus, Type 2/*drug therapy ; Exenatide ; Female ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemic Agents/*therapeutic use ; Lipids/blood ; Longitudinal Studies ; Male ; Middle Aged ; Obesity/*drug therapy ; Peptides/*therapeutic use ; Retrospective Studies ; Venoms/*therapeutic use ; }, abstract = {INTRODUCTION: GLP-1 analogs have been shown to be an effective treatment of type 2 diabetes mellitus (DM-2) and obesity.

OBJECTIVES: Evaluate the efficacy of exenatide LAR on weight loss, glycemic control, blood pressure (BP) and lipid profile, in DM-2 and obesity.

MATERIAL AND METHODS: Retrospective study of patients treated with exenatide LAR for 6 months. Demographic data (age, gender), anthropometric, fasting glucose, glycated hemoglobin (HbA1c), blood pressure and lipid profile were collected at baseline and at 6 months after treatment. We performed a logistic regression analysis to assess possible predictors of efficacy.

RESULTS: 30 patients (17 male, mean age: 61.7 ± 9.5 years old) with DM-2 of 9.7 ± 6.2 years of evolution. HbA1c was reduced by 1.3% (95%CI 1.04-1.57; p <0.001), weight by 2.8 kg (95%CI 1.67-3.96, p <0.001) and BMI by 1.9 kg/m2 (95%CI 1,08-2,93; p <0,001). Total cholesterol decreased by 26.9 mg/dl (95%CI 9.23-38.8, p = 0.003), LDL cholesterol by 21.2 mg/dl (95% CI 7.56-34.9, p = 0.02) and triglycerides by 53.9 mg/dl (95%CI 46.4-77.1 mg/dl, p = 0.004). No statistically significant changes in blood pressure and HDL cholesterol were observed. 53.3% of patients got an HbA1c <7%, 66.6% lost weight, and 43.3% simultaneously achieved both of them. Neither of the studied variables was confirmed as a predictor of treatment response. Regarding side effects, 53.3% reported gastrointestinal discomfort (nausea) and 26.6% reported subcutaneous nodules of spontaneous resolution.

CONCLUSIONS: Treatment with exenatide LA, in obesity and DM-2, has shown beneficial effect on lipid weight, BMI, glycemic control and lipid profile, despite the long duration of diabetes in our patients.}, } @article {pmid25558431, year = {2014}, author = {Vedantham, S and O'Connell, AM and Shi, L and Karellas, A and Huston, AJ and Skinner, KA}, title = {Dedicated Breast CT: Feasibility for Monitoring Neoadjuvant Chemotherapy Treatment.}, journal = {Journal of clinical imaging science}, volume = {4}, number = {}, pages = {64}, pmid = {25558431}, issn = {2156-7514}, support = {R21 CA176470/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVES: In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated.

MATERIALS AND METHODS: Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points - pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologist's segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined.

RESULTS: Tumor volumes from automated and radiologist's segmentations were correlated (Pearson's r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%.

CONCLUSIONS: This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.}, } @article {pmid25550604, year = {2015}, author = {Ruibal, Á and Aguiar, P and Del Rio, MC and Arias, JI and Menéndez-Rodríguez, P and Gude, F and Herranz, M}, title = {Histological grade (HG) in invasive ductal carcinomas of the breast of less than 1 cm: clinical and biological associations during progression from HG1 to HG3.}, journal = {Anticancer research}, volume = {35}, number = {1}, pages = {569-573}, pmid = {25550604}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Tumor Burden ; }, abstract = {AIM: To study the clinical and biological (cellular proliferation and hormone-dependence) associations during the progression of histological grade (HG), from HG1 to HG3, in invasive ductal carcinomas of the breast (IDC) <1 cm.

PATIENTS AND METHODS: The study group included 119 women with IDCs ≤1 cm, aged between 27 and 88 years (median=61 years). The parameters analyzed were: histological grade (HG1: 52; HG2: 45; HG3: 22); axillary lymph node involvement (N); distant metastasis (M); and immunohistochemical expression of estrogen (ER), progesterone (PR) and androgen (AR) receptors, and Ki67, p53 and B-cell lymphoma 2 (BCL2).

RESULTS: Compared to HG3 tumors, HG1s exhibited an increased expression of ER, AR and BCL2, as well as lower expression of p53 and Ki67. In HG1 tumors, significant (p<0.05) associations were found between ER and PR (positive), ER and p53 (negative), ER and Ki67 (negative), PR and AR (positive), PR and p53 (negative), AR and p53 (negative), p53 and BCL2 (negative), and between BCL2 and Ki67 (negative). HG3s only showed significant (p<0.05) associations between ER and Ki-67 (negative) and between BCL2 or Ki-67 (negative). Only two significant relationships (ER-Ki67 and BCL2-Ki67) persisted in all three grades.

CONCLUSION: Our results lead us to the following conclusions: i) compared HG1, HG3 ductal carcinomas exhibited decreased expression of ER, AR and BCL2 and increased expression of p53 and Ki67; and ii) only two significant and negative relations (ER-Ki67 and BCL2-Ki67) persisted in all three grades.}, } @article {pmid25548706, year = {2014}, author = {Shousha, S}, title = {Pleomorphic Invasive Ductal Carcinoma of the Breast in a Patient with Huntington's Disease.}, journal = {Case reports in pathology}, volume = {2014}, number = {}, pages = {979137}, pmid = {25548706}, issn = {2090-6781}, abstract = {A pleomorphic invasive ductal carcinoma developed in a patient with Huntington's disease. The tumour showed marked nuclear pleomorphism and contained large number of bizarre tumour giant cells and abundant abnormal mitoses. Tumour cells showed nuclear vesicles and inclusions similar to those described in nuclei of neural cells in patients with Huntington's disease. The case suggests that, in some patients, tumour morphology may reflect specific individual features.}, } @article {pmid25548268, year = {2015}, author = {Valencia, JF and Vallverdu, M and Rivero, I and Voss, A and de Luna, AB and Porta, A and Caminal, P}, title = {Symbolic dynamics to discriminate healthy and ischaemic dilated cardiomyopathy populations: an application to the variability of heart period and QT interval.}, journal = {Philosophical transactions. Series A, Mathematical, physical, and engineering sciences}, volume = {373}, number = {2034}, pages = {}, pmid = {25548268}, issn = {1364-503X}, mesh = {Adult ; Cardiomyopathy, Dilated/*diagnosis/physiopathology ; Databases, Factual ; Diagnosis, Computer-Assisted ; Electrocardiography ; Female ; Healthy Volunteers ; Heart/*physiology ; Heart Rate ; Humans ; Male ; Middle Aged ; Models, Statistical ; Myocardial Ischemia/*diagnosis/physiopathology ; Normal Distribution ; Signal Processing, Computer-Assisted ; Sympathetic Nervous System ; Time Factors ; }, abstract = {Myocardial ischaemia is hypothesized to stimulate the cardiac sympathetic excitatory afferents and, therefore, the spontaneous changes of heart period (approximated as the RR interval), and the QT interval in ischaemic dilated cardiomyopathy (IDC) patients might reflect this sympathetic activation. Symbolic analysis is a nonlinear and powerful tool for the extraction and classification of patterns in time-series analysis, which implies a transformation of the original series into symbols and the construction of patterns with the symbols. The aim of this work was to investigate whether symbolic transformations of RR and QT cardiac series can provide a better separation between IDC patients and healthy control (HC) subjects compared with traditional linear measures. The variability of these cardiac series was studied during daytime and night-time periods and also during the complete 24 h recording over windows of short data sequences of approximately 5 min. The IDC group was characterized by an increase in the occurrence rate of patterns without variations (0 V%) and a reduction in the occurrence rate of patterns with one variation (1 V%) and two variations (2 V%). Concerning the RR variability during the daytime, the highest number of patterns had 0 V%, whereas the rates of 1 V% and 2 V% were lower. During the night, 1 V% and 2 V% increased at the expense of diminishing 0 V%. Patterns with and without variations between consecutive symbols were able to increase the separation between the IDC and HC groups, allowing accuracies higher than 80%. With regard to entropy measures, an increase in RR regularity was associated with cardiac disease described by accuracy >70% in the RR series and by accuracy >60% in the QTc series. These results could be associated with an increase in the sympathetic tone in IDC patients.}, } @article {pmid25547948, year = {2015}, author = {Moccia, M and Erro, R and Picillo, M and Vassallo, E and Vitale, C and Longo, K and Amboni, M and Santangelo, G and Palladino, R and Nardone, A and Triassi, M and Barone, P and Pellecchia, MT}, title = {Quitting smoking: an early non-motor feature of Parkinson's disease?.}, journal = {Parkinsonism & related disorders}, volume = {21}, number = {3}, pages = {216-220}, doi = {10.1016/j.parkreldis.2014.12.008}, pmid = {25547948}, issn = {1873-5126}, mesh = {Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*epidemiology/*psychology ; Smoking/*epidemiology ; Smoking Cessation/*statistics & numerical data ; }, abstract = {INTRODUCTION: Epidemiological studies report a 60-70% reduced risk of Parkinson's disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated.

METHODS: We recruited 116 de novo PD subjects, and investigated current, former and never smoking, and reasons for smoking cessation among former smokers. Two hundred and thirty-two controls were matched by Propensity Score.

RESULTS: PD subjects and controls were found to be current smokers (7.7 vs. 39.6%), former smokers (43.9 vs. 6.5%) and never smokers (48.2 vs. 53.9%). Logistic regression showed that current smokers were less likely to have PD (p < 0.001; OR: 0.22; 95% CI: 0.10-0.46), while former smokers were more likely to have PD (p < 0.001; OR: 7.6; 95% CI: 4.09-15.75), as compared to never smokers. Fifty-one PD patients reported quitting smoking before PD diagnosis (mean time since cessation 9.4 ± 7.3 years). Most important reasons to quit smoking in PD group were illness different from PD (26 subjects, 51.0%), knowledge of the harmful effects of smoking (24 subjects, 47.0%), and physician's advice (1 subject, 2.0%).

CONCLUSION: The reduced prevalence of current smokers among PD subjects as compared to healthy controls is consistent with previous findings, suggesting a possible neuroprotective effect of smoking. However, it could be due, at least in part, to the increased prevalence of former smokers among PD patients, that were more prone to quit smoking as compared to healthy controls. We suggest that smoking cessation could be an early preclinical condition occurring in PD.}, } @article {pmid25539260, year = {2015}, author = {Chadashvili, T and Ghosh, E and Fein-Zachary, V and Mehta, TS and Venkataraman, S and Dialani, V and Slanetz, PJ}, title = {Nonmass enhancement on breast MRI: review of patterns with radiologic-pathologic correlation and discussion of management.}, journal = {AJR. American journal of roentgenology}, volume = {204}, number = {1}, pages = {219-227}, doi = {10.2214/AJR.14.12656}, pmid = {25539260}, issn = {1546-3141}, mesh = {Adult ; Aged ; *Algorithms ; Breast Neoplasms/*pathology ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {OBJECTIVE: The purpose of this article is to review the varied appearances and associated diagnoses of nonmass enhancement on breast MRI with radiologic-pathologic correlation.

CONCLUSION: Knowledge of the distribution and internal characteristics of these findings is helpful to determine when core needle biopsy is indicated. Correlating imaging with pathologic findings is critical in making appropriate recommendations regarding clinical management.}, } @article {pmid25536589, year = {2014}, author = {Budakoglu, B and Altundag, K and Aksoy, S and Kaplan, MA and Ozdemir, NY and Berk, V and Ozkan, M and Algin, E and Kandemir, N and Dogu, GG and Harputluoglu, H and Arslan, UY and Coskun, U and Isikdogan, A and Oksuzoglu, B}, title = {Outcome of 561 non-metastatic triple negative breast cancer patients: multi-center experience from Turkey.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {19}, number = {4}, pages = {872-878}, pmid = {25536589}, issn = {1107-0625}, mesh = {Breast Neoplasms ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; *Lymphatic Metastasis ; Middle Aged ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptors, Estrogen ; Receptors, Progesterone ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology/*therapy ; Turkey ; }, abstract = {PURPOSE: Triple-negative breast cancers account for 15% of breast carcinomas and, when present as early-stage disease, they are associated with higher rates of recurrence and early distant metastasis risk when compared to hormone receptor positive and human epidermal growth factor receptor (HER-2) positive breast cancers. In this study we aimed to explore the basic clinicopathological characteristics, prognostic factors and recurrence patterns of non-metastatic triple negative breast cancer patients.

METHODS: In this study 561 non-metastatic triple-negative breast cancer female patients admitted to 8 different cancer centers in Turkey between 2000 and 2010 were retrospectively evaluated through their medical records, to identify the basic clinico-pathological characteristics, prognostic factors and recurrence patterns.

RESULTS: The ratio of triple-negative breast cancer was 12%. The median age of patients was 48 years, of whom 311 (55.4%) were premenopausal. The majority had early-stage breast cancer at the time of diagnosis (16.8% stage I, 48.1% stage II, 35.1 % stage III) and the most commonly identified variant was invasive ductal carcinoma (84.1%). Grade II and III tumors were 27.1 and 48.5%, respectively. Adjuvant chemotherapy was administered to 90.5% of women and adjuvant radiotherapy to 41.2%. Median patient follow up was 28 months (range 3-290). During the follow up period 134 (23.8%) patients developed metastatic disease. In most of these cases, metastatic sites were bone, soft tissue, and lung. Factors affecting disease free survival (DFS) and overall survival (OS) were age (both p<0.001), lymph node involvement (both p<0.001), lymphovascular invasion (LVI) (p<0.001 and p=0.004, respectively), tumor stage (both p<0.001), adjuvant administration of anthracycline-based chemotherapy (both <0.001) and type of surgery (not significant for DFS but p=0.05 for OS). Three-year DFS and OS were 72.0 and 93.0%, respectively.

CONCLUSION: Age, lymph node involvement, LVI, stage, and adjuvant chemotherapy were determined as prognostic factors for DFS and OS. The most common recurrence sites were bone, soft tissue and the lung. Further prospective randomised trials are needed to confirm the prognostic and predictive factors identified in this study.}, } @article {pmid25535588, year = {2015}, author = {Marinova, L and Hadjieva, T and Kanchev, E and Vicheva, S}, title = {Synchronous primary mammary osteosarcoma and invasive breast cancer. A case report - Pathohistological and immunohistochemical analysis.}, journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology}, volume = {20}, number = {1}, pages = {72-76}, pmid = {25535588}, issn = {1507-1367}, abstract = {Primary osteogenic sarcoma of the breast is a rare neoplasm, diagnosed mainly by pathohistological and immunohistochemical analysis. We hereby present a case of primary osteogenic sarcoma in the right breast of a 62-year-old woman with synchronous appearance of an invasive ductal carcinoma. Clinical findings are manifested with two separate painless formations 2.5 cm/2 cm and 1.5 cm/1 cm in size, located on the border of the upper and lower lateral quadrant of the right breast. No axillary lymphadenopathy was diagnosed. The pathohistological and immunohistochemistry findings of both tumors revealed a synchronous manifestation of two distinct neoplasms - epithelial and non-epithelial. Multimodality treatment consisted of Patey's radical mastectomy; 3 cycles of adjuvant chemotherapy; postoperative 50 Gy radiotherapy to the chest wall followed by additional 3 cycles of chemotherapy and anti-estrogen hormonotherapy. Due to the rarity of osteogenic mammary sarcoma, even more so in a combination with epithelial breast tumors, its clinical features are unclear and optimal treatment remains controversial. Considering the poor prognosis of the combination of both malignomas, we discuss a number of diagnostic and therapeutic issues.}, } @article {pmid25534095, year = {2014}, author = {Shi, J and Lü, X and Wang, B and Daudan, L and Yanan, W and Yuhui, B and Zhenfeng, M}, title = {[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].}, journal = {Zhonghua yi xue za zhi}, volume = {94}, number = {36}, pages = {2804-2807}, pmid = {25534095}, issn = {0376-2491}, mesh = {Becaplermin ; *Breast Neoplasms ; Cell Line, Tumor ; *Cell Proliferation ; Down-Regulation ; Humans ; Proto-Oncogene Proteins c-sis ; Y-Box-Binding Protein 1 ; }, abstract = {OBJECTIVE: To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation.

METHODS: Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation.

RESULTS: YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P < 0.05).YB1 expression levels increased in PDGF-BB stimulated SK-BR-3 cells in a dose-dependent manner.

CONCLUSION: A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.}, } @article {pmid25527452, year = {2015}, author = {Huang, KT and Tan, D and Chen, KE and Walker, AM}, title = {Blockade of estrogen-stimulated proliferation by a constitutively-active prolactin receptor having lower expression in invasive ductal carcinoma.}, journal = {Cancer letters}, volume = {358}, number = {2}, pages = {152-160}, doi = {10.1016/j.canlet.2014.12.031}, pmid = {25527452}, issn = {1872-7980}, mesh = {Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Estradiol/metabolism/pharmacology ; Estrogens/*metabolism/pharmacology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Neoplasm Invasiveness ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, Prolactin/chemistry/genetics/*metabolism ; }, abstract = {A comprehensive understanding of prolactin's (PRL's) role in breast cancer is complicated by disparate roles for alternatively-spliced PRL receptors (PRLR) and crosstalk between PRL and estrogen signaling. Among PRLRs, the short form 1b (SF1b) inhibits PRL-stimulated cell proliferation. In addition to ligand-dependent PRLRs, constitutively-active varieties, missing the S2 region of the extracellular domain (ΔS2), naturally occur. Expression analysis of the ΔS2 version of SF1b (ΔS2SF1b) showed higher expression in histologically-normal contiguous tissue versus invasive ductal carcinoma. To determine the function of ΔS2SF1b, a T47D breast cancer line with inducible expression was produced. Induction of ΔS2SF1b blocked estrogen-stimulated cell proliferation. Unlike intact SF1b, induction of ΔS2SF1b had no effect on PRL-mediated activation of Stat5a. However induction inhibited estrogen's stimulatory effects on serine-118 phosphorylation of estrogen receptor α, serine-473 phosphorylation of Akt, serine-9 phosphorylation of GSK3β, and c-myc expression. In addition, induction of ΔS2SF1b increased expression of the cell cycle-inhibiting protein, p21. Thus, increased expression of ΔS2SF1b, such as we demonstrate occurs with the selective PRLR modulator, S179D PRL, would create a physiological state in which estrogen-stimulated proliferation was inhibited, but differentiative responses to PRL were maintained.}, } @article {pmid25523373, year = {2015}, author = {Zhang, L and Jia, N and Han, L and Yang, L and Xu, W and Chen, W}, title = {Comparative analysis of imaging and pathology features of mucinous carcinoma of the breast.}, journal = {Clinical breast cancer}, volume = {15}, number = {2}, pages = {e147-54}, doi = {10.1016/j.clbc.2014.11.005}, pmid = {25523373}, issn = {1938-0666}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Breast Neoplasms/*pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/methods ; Mammography ; Middle Aged ; }, abstract = {BACKGROUND: The purpose of the study was to explore the relationship between the mammographic features, MR features, and pathological manifestations of PMBCs and MMBCs.

PATIENTS AND METHODS: Twenty-seven cases of mucinous breast carcinoma confirmed in surgical biopsy, including 18 cases of PMBC and 9 cases of MMBC, were included (mean age, 51.2 and 53.3 years, respectively). All patients underwent preoperative mammography, and 13 of 27 patients underwent preoperative MR imaging (MRI), 4 of whom underwent diffusion-weighted imaging. All mammographic and MRI information, such as the size, shape, borders of the mass, and evidence of calcification were classified according to the American Collage of Radiology (ACR) Breast Imaging-Reporting And Data System (BI-RADS) mammography/MR lexicon. The signal intensity of the mass was visually classified as low, iso, high, strongly high, or mixed in accordance with surrounding mammary gland tissues. The pattern of internal enhancement of the mass included homogeneity, rim enhancement, central enhancement, dark internal septation, and enhancing internal septation. The kinetic curve pattern was categorized into 3 types: persistent, plateau, or washout.

RESULTS: There was no significant difference PMBC and MMBC in the shape of tumor, calcifications, T2 signal intensity, internal mass enhancement, kinetic curve assessment, and positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermalgrowth factor receptor-2 (HER-2). The PMBC tumors were larger than MMBC tumors (P < .001), and MMBC tended to present as an ill-circumscribed mass (P = .043). The ADC values of the 5 lesions of 4 mucinous breast carcinoma (MBCs) ranged from 0.771 to 2.252 × 10(3) mm(2)/s, markedly greater than that of conventional infiltrating ductal carcinoma (IDC). The ADC values of MMBC were visibly less than those of PMBC for the former mixed with massive tumor cells of IDC.

CONCLUSION: MBC commonly presented as masses with well circumscribed, round, or lobular shapes. The remaining cases presented with focal symmetry. The rate of regional nodal involvement of MBC was less than that of IDC. The MR features of PMBC included benign (homogenous intensity on T1-weighted imaging [WI] and T2-WI, persistent enhancement pattern) and malignant characteristics (rim or heterogeneous enhancement). The ADC values of MBC were greater than those of benign lesions and other malignant tumors. We believe that the combination of mammography and Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may help to improve the diagnostic accuracy of MBC.}, } @article {pmid25523328, year = {2014}, author = {Lappalainen, AK and Vaittinen, E and Junnila, J and Laitinen-Vapaavuori, O}, title = {Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications.}, journal = {Acta veterinaria Scandinavica}, volume = {56}, number = {1}, pages = {89}, pmid = {25523328}, issn = {1751-0147}, mesh = {Animals ; Calcinosis/diagnostic imaging/epidemiology/etiology/*veterinary ; Dog Diseases/diagnostic imaging/*epidemiology/etiology ; Dogs ; Finland/epidemiology ; Intervertebral Disc Degeneration/diagnostic imaging/epidemiology/etiology/*veterinary ; Intervertebral Disc Displacement/diagnostic imaging/epidemiology/etiology/*veterinary ; Mass Screening/veterinary ; Radiography ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC. A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0 = no calcifications, grade 1 = 1 - 2 calcifications, grade 2 = 3 - 4 calcifications and grade 3 = 5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian.

RESULTS: IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P < 0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P < 0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD.

CONCLUSIONS: Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.}, } @article {pmid25522006, year = {2015}, author = {Norddin, N and Power, C and Watson, G and Cowin, G and Kurniawan, ND and Gluch, L and Bourne, RM}, title = {Microscopic diffusion properties of fixed breast tissue: Preliminary findings.}, journal = {Magnetic resonance in medicine}, volume = {74}, number = {6}, pages = {1733-1739}, doi = {10.1002/mrm.25555}, pmid = {25522006}, issn = {1522-2594}, mesh = {Adult ; Breast/*chemistry/*pathology ; Breast Neoplasms/*chemistry/*pathology ; Diffusion ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Fixatives/chemistry ; Formaldehyde/chemistry ; Humans ; Image Interpretation, Computer-Assisted/*methods ; In Vitro Techniques ; Middle Aged ; Pilot Projects ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To investigate the microscopic diffusion properties of formalin-fixed breast tissue.

METHODS: Diffusion microimaging was performed at 16.4T with 40-μm isotropic voxels on two normal and two cancer tissue samples from four patients. Results were correlated with histology of the samples.

RESULTS: Diffusion-weighted images and mean diffusivity maps demonstrated distinct diffusivity differences between breast tissue components. Mean diffusivity (MD) in normal tissue was 0.59 ± 0.24 μm(2) /ms for gland lobule (voxels containing epithelium and intralobular stroma) and 1.23 ± 0.34 μm(2) /ms for interlobular fibrous stroma. In the cancer samples, MD = 0.45 ± 0.23 μm(2) /ms for invasive ductal carcinoma (voxels contain epithelium and intralobular stroma) and 0.61 ± 0.35 μm(2) /ms for ductal carcinoma in situ. There were significant MD differences between all tissue components (P < 0.005), except between gland lobule and ductal carcinoma in situ (P = 0.71). The low diffusivity of epithelium-rich cancer tissue and of normal epithelium relative to its supporting fibrous stroma was similar to that reported for prostate tissue and the esophageal wall.

CONCLUSION: Diffusion microimaging demonstrates distinct diffusivity differences between breast tissue glandular structures. Low diffusivity may be a distinctive feature of mammalian epithelia.}, } @article {pmid25521345, year = {2015}, author = {van der Velden, TA and Italiaander, M and van der Kemp, WJ and Raaijmakers, AJ and Schmitz, AM and Luijten, PR and Boer, VO and Klomp, DW}, title = {Radiofrequency configuration to facilitate bilateral breast (31) P MR spectroscopic imaging and high-resolution MRI at 7 Tesla.}, journal = {Magnetic resonance in medicine}, volume = {74}, number = {6}, pages = {1803-1810}, doi = {10.1002/mrm.25573}, pmid = {25521345}, issn = {1522-2594}, mesh = {Amplifiers, Electronic ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diffusion Magnetic Resonance Imaging/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; Female ; Humans ; Image Enhancement/*instrumentation ; Magnetic Resonance Spectroscopy/*instrumentation ; Magnetics/*instrumentation ; Molecular Imaging/methods ; Phosphorus Isotopes/pharmacokinetics ; Radio Waves ; Radiopharmaceuticals/pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; Transducers ; }, abstract = {PURPOSE: High-resolution MRI combined with phospholipid detection may improve breast cancer grading. Currently, configurations are optimized for either high-resolution imaging or (31) P spectroscopy. To be able to perform both imaging as well as spectroscopy in a single session, we integrated a (1) H receiver array into a (1) H-(31) P transceiver at 7T. To ensure negligible signal loss due to coupling between elements, we investigated the use of a floating decoupling loop to enable bilateral MRI and (31) P MRS.

METHODS: Two quadrature double-tuned radiofrequency coils were designed for bilateral breast MR with active detuning at the (1) H frequency. The two coils were placed adjacent to each other and decoupled for both frequencies with a single resonant floating loop. Sensitivity of the bilateral configuration, facilitating space for a 26-element (1) H receive array, was compared with a transceiver configuration.

RESULTS: The floating loop was able to decouple the elements over 20 dB for both frequencies. Enlargement of the elements, to provide space for the receivers, and the addition of detuning electronics altered the (31) P sensitivity by 0.4 dB.

CONCLUSION: Dynamic contrast-enhanced scans of 0.7 mm isotropic, diffusion-weighted imaging, and (31) P MR spectroscopic imaging can be acquired at 7T in a single session as demonstrated in a patient with invasive ductal carcinoma.}, } @article {pmid25520870, year = {2014}, author = {Zhang, W and Lin, ZC and Zhang, TX and Liu, S and Liu, X and Liu, JJ and Niu, Y}, title = {TrkC expression predicts favorable clinical outcome in invasive ductal carcinoma of breast independent of NT-3 expression.}, journal = {American journal of cancer research}, volume = {4}, number = {6}, pages = {811-823}, pmid = {25520870}, issn = {2156-6976}, abstract = {BACKGROUND: TrkC, a member of neurotrophin receptor family, functions not only as an oncogene, but also act as a tumor suppressor via a manner of dependence receptor in human malignant tumors. Little is known on the action of TrkC for the clinical prognosis and the progression of breast cancer according to the availability of its ligand NT-3. We sought to investigate the prognostic relevance of NT-3-TrkC axis in breast cancer and estimate its role during the process of breast cancer progression.

METHODS: 236 cases of invasive ductal carcinoma (IDC), 60 pure ductal carcinoma in situ (DCIS) and 30 normal breast tissue (NBT) between 2004 and 2005 were included in the study. Spearman's rank correlation test was used to analyze the association of NT-3-TrkC expression and breast cancer progression. The Kaplan-Meier method and Cox proportional hazards model were performed to identify the relevant prognostic factors.

RESULTS: 50.4% IDC tumors displayed absent or low TrkC expression, while 49.6% was high TrkC expression. TrkC expression was negatively associated with lymph node metastasis (P = 0.029) and tumor proliferation (P = 0.015). Patients with lower TrkC expressing tumors had a higher risk of recurrence (odds ratio, 0.401; 95% confidence interval, 0.207-0.778; P = 0.007). The layered analysis indicated that patients with high TrkC expression tumors had a favor disease-free survival whether NT-3 and TrkC were co-expressed or solitarily expressed in the tumor (P = 0.000). NT-3 was demonstrated to be not a predictor of IDC patients' prognosis. But NT-3 expression was inversely correlated with the progression of breast cancer (r = -0.341, P = 0.000), since more IDC tumors showed high NT-3 expression than DCIS tumors (51.7% vs. 25.9%), while no NBT showed high NT-3 expression, as well.

CONCLUSION: The study indicates TrkC expression reduces tumor relapse independent of NT-3 availability in the IDC. Elevated NT-3 expression contributes to the progression of breast cancer.}, } @article {pmid25518541, year = {2014}, author = {Andjelić-Dekić, N and Božović-Spasojević, I and Milošević, S and Matijašević, M and Karadžić, K}, title = {A rare case of isolated adrenal metastasis of invasive ductal breast carcinoma.}, journal = {Srpski arhiv za celokupno lekarstvo}, volume = {142}, number = {9-10}, pages = {597-601}, doi = {10.2298/sarh1410597a}, pmid = {25518541}, issn = {0370-8179}, mesh = {Adrenal Gland Neoplasms/drug therapy/*secondary ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; Trastuzumab/therapeutic use ; }, abstract = {INTRODUCTION: Isolated adrenal metastases of invasive ductal breast carcinoma are extremely rare. We report a case with isolated left adrenal metastases, verified three years after diagnosed breast carcinoma.

CASE OUTLINE: A 58-year-old female patient with a right breast tumor, clinically staged as IIIA (T2N2M0) started neoadjuvant anthracycline chemotherapy after biopsy which revealed invasive ductal breast carcinoma. Immunohistochemical findings of tumor biopsy showed hormonal steroid receptors for estrogen and progesterone negative, and human epidermal growth factor receptor 2 (HER2) positive. After 4 cycles of chemotherapy and partial tumor regression the patient underwent radical mastectomy. Definite histopathological analysis confirmed the diagnosis of invasive ductal carcinoma. The patient continued treatment with adjuvant chemotherapy to cumulative dose of anthracyclines, postoperative radiotherapy and adjuvant trastuzumab for one year. Three years later abdominal computerized tomography showed tumor in the left adrenal gland as the only metastatic site. Left adrenalectomy was performed and histopathological finding confirmed breast cancer metastases. Postoperatively, the patient received 6 cycles of docetaxel with trastuzumab and continued trastuzumab until disease progression. One year after left adrenalectomy control abdominal computerized tomography showed a right adrenal tumor with retroperitoneal lymphadenopathy. Treatment with capecitabine was continued for one year, but eventually she developed brain metastasis causing lethal outcome.

CONCLUSION: In order to better understand metastatic pathways of invasive ductal breast carcinoma, publications of individual patient cases diagnosed with rare metastatic sites should be encouraged. This might improve our understanding of metastatic behavior of breast cancer and stimulate further clinical research.}, } @article {pmid25516401, year = {2015}, author = {Eggemann, H and Kalinski, T and Ruhland, AK and Ignatov, T and Costa, SD and Ignatov, A}, title = {Clinical implications of growth pattern and extension of tumor-associated intraductal carcinoma of the breast.}, journal = {Clinical breast cancer}, volume = {15}, number = {3}, pages = {227-233}, doi = {10.1016/j.clbc.2014.11.008}, pmid = {25516401}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nipples/*pathology ; Precancerous Conditions/*pathology ; Retrospective Studies ; }, abstract = {UNLABELLED: Tumor specimens from 410 patients with primary invasive breast cancer were investigated to identify the clinically relevant features of tumor-associated intraductal component (IDC) surrounding invasive breast cancer. A tumor-associated IDC associated with invasive tumor was mostly localized between the tumor and nipple. Thus, segmental resection of breast tissue is suggested.

INTRODUCTION: The goal of the present study was to identify the clinically relevant features of tumor-associated intraductal component (IDC) surrounding invasive breast cancer.

PATIENTS AND METHODS: The tumor specimens from 410 patients with primary invasive breast cancer were investigated. The distance between the surgical margins and tumor edge (invasive and intraductal areas) was measured prospectively.

RESULTS: Of the 410 investigated patients, 395 were eligible for analysis. An IDC was observed in 241 specimens (61.0%) and was associated with a younger age at diagnosis, postmenopausal status, and positive estrogen receptor, progesterone receptor, and human epidermal growth factor 2 (HER2) expression status. Most cases with tumor-associated ductal carcinoma in situ (DCIS) were found in the upper-outer quadrants of the breasts. An extended intraductal component (EIC) tended to be present in the outer and lower quadrants of the breasts. In the study cohort of 187 patients with tumor-associated DCIS, 1496 surgical margins were investigated. IDC was associated with invasive tumor growth predominantly in the nipple direction. The nipple-associated growth of DCIS correlated with patient age > 40 years, tumor size ≤ 2 cm, poor histologic differentiation of the noninvasive and invasive components, and positive estrogen and progesterone receptor status and negative HER2 status.

CONCLUSIONS: Our data provide evidence that in patients with primary breast cancer, the EIC areas will be mostly segmentally localized between the invasive tumor and the nipple. Therefore, if EIC is present or assumed, surgery should consist of segmental resection of the breast tissue, at least in patients with breast cancer who are > 40 years old, with a tumor size of < 2 cm, and with hormone receptor-positive and HER2-negative, poorly differentiated tumors.}, } @article {pmid25506536, year = {2014}, author = {Becker, H and Billington, ME}, title = {A Novel Approach to the Management of Margin-positive DCIS in Nipple-sparing Mastectomy.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {2}, number = {11}, pages = {e253}, pmid = {25506536}, issn = {2169-7574}, abstract = {Nipple-sparing mastectomy (NSM) is gaining acceptance as an oncologically sound and cosmetically superior mastectomy technique. Debate exists over the management of positive margins near the nipple-areola complex. This case report presents a novel approach to the management of margin-positive ductal carcinoma in situ in NSM. A 50-year-old white female with invasive ductal carcinoma underwent NSM. Intraoperative pathology indicated the presence of DCIS-positive retroareolar margins. Revision through a direct vertical nipple incision allowed for adequate surgical revision and pathologic evaluation of the retroareolar breast tissue while maintaining the nipple-areola skin and primary mastectomy incision. This novel approach ensures negative margins, allows superior cosmetic outcome, and improves patient autonomy in decision making. The technique may translate to NSM patients with positive retroareolar margins or false-negative margins.}, } @article {pmid25506489, year = {2014}, author = {Lakshmaiah, KC and Das, U and Suresh, TM and Lokanatha, D and Babu, GK and Jacob, LA and Babu, S}, title = {A study of triple negative breast cancer at a tertiary cancer care center in southern India.}, journal = {Annals of medical and health sciences research}, volume = {4}, number = {6}, pages = {933-937}, pmid = {25506489}, issn = {2141-9248}, abstract = {BACKGROUND: Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group of tumors that by definition lack estrogen and progesterone receptors and amplification of the HER-2 gene. The majority of the tumors classified as TNBCs are highly malignant, patients are usually young and only a subgroup of patients responds to conventional chemotherapy with a favorable prognosis. Various studies have been reported in western literature on TNBCs, all highlighting the poor prognosis of this subtype. However, extensive data from India is lacking.

AIM: The aim of this study was to analyze the epidemiological and clinical profile of TNBCs at our institute.

MATERIALS AND METHODS: This was the retrospective study carried out in Tertiary Cancer Care Center in South India. Case files of all breast cancer patients were reviewed from the hospital database registered in 1 year and TNBC patients were selected for the study. Patient's characteristic, treatment, and histological features were analyzed.

RESULTS: A total of 322 patients were registered during the period of 1 year and 26% (84/322) of total patients were TNBC. Median age of presentation was 44.5 years. About 94% (79/84) of patients had first full-term delivery before the age of 30 years. The most common presenting symptom was left sided breast lump. Locally advanced and early breast cancer (EBC) was 51% (43/84) and 42% (36/84), respectively. Metastatic breast cancer was seen in five patients. The highest numbers of patients were node negative disease (36.9%) [31/84], followed by N1 30.95% (26/84). Most of the patients had high-grade tumor. 94% (34/36) of cases of EBC had undergone upfront modified radical mastectomy. Invasive ductal carcinoma was the predominant histology except one who had medullary carcinoma. Twenty-four patients received neoadjuvant chemotherapy (NACT). There was no pathological complete remission, but all patients responded to NACT. Metastatic disease was seen in five patients. All patients had bone metastasis.

CONCLUSIONS: TNBCs are highly aggressive subtype, with high grade with limited treatment options and very poor prognosis. Incidence is more in our country than the western literature. Even in our country also the incidence is varies in different region. TNBCs are significantly associated with young aged patients. There was a lack of association between tumor size and lymph node positivity.}, } @article {pmid25501850, year = {2014}, author = {Ben-David, BM and Eidels, A and Donkin, C}, title = {Effects of aging and distractors on detection of redundant visual targets and capacity: do older adults integrate visual targets differently than younger adults?.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e113551}, pmid = {25501850}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; *Aging ; Attention ; Humans ; *Reaction Time ; Visual Perception/*physiology ; Young Adult ; }, abstract = {In the redundant target effect, participants respond faster with two (redundant) targets. We compared the magnitude of this effect in younger and older adults, with and without distractors, in a simple visual-detection task. We employed additional measures that allow non-parametric assessment of performance (Townsend's capacity coefficient) and parametric estimates (Linear Ballistic Accumulator model). Older participants' latencies were slower, especially in the presence of distractors, and their calculated capacity indicators increased with distractors. Parametric estimates indicated that these increases were generated by the older adults' increased difficulty in inhibiting the distractors, and not the results of either improved detection of redundant-targets, or of a generalized slowing of processing.}, } @article {pmid25496835, year = {2015}, author = {Yoo, SH and Park, IA and Chung, YR and Kim, H and Lee, K and Noh, DY and Im, SA and Han, W and Moon, HG and Lee, KH and Ryu, HS}, title = {A histomorphologic predictive model for axillary lymph node metastasis in preoperative breast cancer core needle biopsy according to intrinsic subtypes.}, journal = {Human pathology}, volume = {46}, number = {2}, pages = {246-254}, doi = {10.1016/j.humpath.2014.10.017}, pmid = {25496835}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Predictive Value of Tests ; *Sentinel Lymph Node Biopsy/methods ; }, abstract = {The aim of this study is construction of a pathologic nomogram that can predict axillary lymph node metastasis (LNM) for each intrinsic subtype of breast cancer with regard to histologic characteristics in breast core needle biopsy (CNB) for use in routine practice. A total of 534 CNBs with invasive ductal carcinoma classified into 5 intrinsic subtypes were enrolled. Eighteen clinicopathological characteristics and 8 molecular markers used in CNB were evaluated for construction of the best predictive model of LNM. In addition to conventional parameters including tumor multiplicity (P < .001), tumor size (P < .001), high histologic grade (P = .035), and lymphatic invasion (P = .017), micropapillary structure (P < .001), the presence of small cell-like crush artifact (P = .001), and overexpression of HER2 (P = .090) and p53 (P = .087) were proven to be independent predictive factors for LNM. A combination of 8 statistically independent parameters yielded the strongest predictive performance with an area under the curve of 0.760 for LNM. A combination of 6 independent variables, including tumor number, tumor size, histologic grade, lymphatic invasion, micropapillary structure, and small cell-like crush artifact produced the best predictive performance for LNM in luminal A intrinsic subtype (area under the curve, 0.791). Thus, adding these combinations of clinical and morphologic parameters in preoperative CNB is expected to enhance the accuracy of prediction of LNM in breast cancer, which might serve as another valuable tool in determining optimal surgical strategies for breast cancer patients.}, } @article {pmid25494117, year = {2014}, author = {Krishnappa, R and Chikaraddi, SB and Deshmane, V}, title = {Primary synchronous bilateral breast cancer.}, journal = {Indian journal of cancer}, volume = {51}, number = {3}, pages = {256-258}, doi = {10.4103/0019-509X.146762}, pmid = {25494117}, issn = {1998-4774}, abstract = {Background: Primary synchronous bilateral breast cancer (PSBBC) is a rare clinical entity. The reported incidence ranges between 0.3% and 12%. There are several controversial issues regarding PSBBC pertaining to the diagnostic criteria, nomenclature, and management policies. Materials and Methods: Fourteen cases of PSBBC treated between 2001 to 2010 at our institute were retrospectively analysed in regards to demographic data, management and follow up. Results: PSBBC constituted 0.19% of total breast cancer patients at our institute. Age ranged from 28 to 78 years. PSBBC were detected by clinical examination in eight cases and by mammography in six cases. Twelve patients underwent bilateral modified radical mastectomy, one had unilateral mastectomy on one side and breast conservation on the other side and one patient has bilateral breast conservation. Majority of patients belonged to stage 2 and stage 3. All patients were found to have invasive ductal carcinoma. Five cases were ER/PR positive and 8 patients were triple hormone receptor negative. Eight patients received unilateral and six received bilateral adjuvant radiotherapy. Nine patients received adjuvant chemotherapy. 5 patients received adjuvant hormonal therapy. Median follow up of patients was 15.4 months. Conclusion: PSBBC is a rare event warranting awareness and screening of the contralateral breast in patients with unilateral breast cancer. These patients require individualized treatment planning based on the tumor factors of the index lesion. Further multi institutional prospective studies are needed for adequate understanding of management of PSBBC.}, } @article {pmid25493218, year = {2014}, author = {Wazir, U and Mokbel, K}, title = {Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine.}, journal = {World journal of clinical oncology}, volume = {5}, number = {5}, pages = {795-799}, pmid = {25493218}, issn = {2218-4333}, abstract = {Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.}, } @article {pmid25491214, year = {2014}, author = {Albasri, A and Hussainy, AS and Sundkji, I and Alhujaily, A}, title = {Histopathological features of breast cancer in Al-Madinah region of Saudi Arabia.}, journal = {Saudi medical journal}, volume = {35}, number = {12}, pages = {1489-1493}, pmid = {25491214}, issn = {1658-3175}, mesh = {Adenocarcinoma, Mucinous/epidemiology/pathology ; Adult ; Age Distribution ; Aged ; Axilla ; Breast Neoplasms/*epidemiology/pathology ; Breast Neoplasms, Male/*epidemiology/pathology ; Carcinoma in Situ/epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/pathology ; Carcinoma, Lobular/*epidemiology/pathology ; Carcinoma, Medullary/epidemiology/pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Male ; Middle Aged ; Neoplasm Staging ; Paget's Disease, Mammary/epidemiology/pathology ; Saudi Arabia/epidemiology ; Tumor Burden ; Young Adult ; }, abstract = {OBJECTIVES: To observe the frequency of breast cancer among Saudi patients and to highlight the age variations and features of advanced cancer.

METHODS: A retrospective study of breast cancer biopsies from all Saudi patients performed between January 2006 and December 2013 in King Fahad Hospital, Al-Madinah, Kingdom of Saudi Arabia. All the available demographic and tumor related data was analyzed.

RESULTS: Of 1005 breast tissues reviewed, 982 specimens were from female, and 23 from male patients. In females, 398 specimens (40.5%) were diagnosed as malignant. Invasive ductal carcinoma (IDC) (85.2%) was most common, followed by ductal carcinoma in situ (8%), and invasive lobular carcinoma (2.7%). The mean age of Saudi females with IDC was 46.9 years. Approximately 48.7% IDC were Grade III tumors. A tumor size >2.5 cm  was found in 61.1% patients, whereas axillary nodal metastasis was present in 57.1% and lympho-vascular invasion in 64.1% who underwent axillary nodal dissection. In males, 4 specimens (17.4%) were malignant (all IDC).

CONCLUSION: Our finding are consistent with previous reports of breast cancer being diagnosed in younger age group, in advanced stages, and with features of aggressive behavior; which signals the urgency for implementation of breast screening programs. }, } @article {pmid25486426, year = {2015}, author = {Chen, C and Wang, X and Xiong, X and Liu, Q and Huang, Y and Xu, Q and Hu, J and Ge, G and Ling, K}, title = {Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.}, journal = {Oncogene}, volume = {34}, number = {35}, pages = {4635-4646}, pmid = {25486426}, issn = {1476-5594}, support = {R01 CA149039/CA/NCI NIH HHS/United States ; R01 DK090038/DK/NIDDK NIH HHS/United States ; R01 DK099160/DK/NIDDK NIH HHS/United States ; 1R01CA149039-01A1/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; ErbB Receptors/metabolism ; Female ; Gene Knockdown Techniques ; Lung Neoplasms/*enzymology/secondary ; Mammary Neoplasms, Experimental/*enzymology/pathology ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; Phosphotransferases (Alcohol Group Acceptor)/*genetics/metabolism ; Protein Processing, Post-Translational ; RNA, Small Interfering/genetics ; }, abstract = {Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.}, } @article {pmid25483573, year = {2017}, author = {Zhu, H and Li, K and Dong, DD and Fu, J and Liu, DD and Wang, L and Xu, G and Song, LH}, title = {Spindle cell metaplastic carcinoma of breast: A clinicopathological and immunohistochemical analysis.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {13}, number = {2}, pages = {e72-e78}, doi = {10.1111/ajco.12322}, pmid = {25483573}, issn = {1743-7563}, mesh = {Adult ; Aged ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma/*metabolism/*pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {AIM: To better characterize spindle cell metaplastic carcinoma (SpCMC) of breast, a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma.

METHODS: We presented herein 19 cases of metaplastic breast carcinoma with dominant spindle cell component. All cases were clinically of breast origin, showed more than 80% spindle morphology, 10 cases exhibited pure spindled morphology, 8 contained invasive ductal carcinoma (IDC) and 1 presented with ductal carcinoma in situ elements.

RESULTS: Immunohistochemical studies showed evidence suggesting myoepithelial and epithelial differentiation as exhibited by immunoreactivity for at least one myoepithelial and epithelial markers in all pure spindle cell components. IDC group showed 21.7% of axillary lymph nodes metastasis rate, whereas the axillary lymph node metastasis rate of the SpCMC group was 1.3%, significantly lower than that of the IDC group (P < 0.001). Immunohistochemical staining of IDC exhibited higher degrees of positivity for ER, PR and Her2 (90, 60 and 30%, respectively) when compared with the SpCMC group, which showed a positive degree of 5.2, 5.2 and 10.5% for ER, PR and Her2, respectively (P < 0.001).

CONCLUSION: Based on this series, SpCMC is a rare variant of metaplastic breast carcinoma with the distinct histopathological and immunohistochemical features. The biological behaviors of SpCMC, like axillary lymph node status, were quite different from that of IDC, suggesting that it may act as an independent pathologic subtype. Immunohistochemical analysis of a panel of epithelial and myoepithelial markers could contribute to the pathologic diagnosis of SpCMC.}, } @article {pmid25481753, year = {2015}, author = {Yasaka, R and Ohba, K and Schwinghamer, MW and Fletcher, J and Ochoa-Corona, FM and Thomas, JE and Ho, SYW and Gibbs, AJ and Ohshima, K}, title = {Phylodynamic evidence of the migration of turnip mosaic potyvirus from Europe to Australia and New Zealand.}, journal = {The Journal of general virology}, volume = {96}, number = {Pt 3}, pages = {701-713}, doi = {10.1099/jgv.0.000007}, pmid = {25481753}, issn = {1465-2099}, mesh = {Australia ; Biological Evolution ; Brassicaceae/*virology ; Europe ; Genome, Viral ; Molecular Sequence Data ; Mosaic Viruses/genetics/*isolation & purification ; New Zealand ; Phylogeny ; Phylogeography ; Plant Diseases/*virology ; Reassortant Viruses ; Time Factors ; }, abstract = {Turnip mosaic virus (TuMV) is a potyvirus that is transmitted by aphids and infects a wide range of plant species. We investigated the evolution of this pathogen by collecting 32 isolates of TuMV, mostly from Brassicaceae plants, in Australia and New Zealand. We performed a variety of sequence-based phylogenetic and population genetic analyses of the complete genomic sequences and of three non-recombinogenic regions of those sequences. The substitution rates, divergence times and phylogeographical patterns of the virus populations were estimated. Six inter- and seven intralineage recombination-type patterns were found in the genomes of the Australian and New Zealand isolates, and all were novel. Only one recombination-type pattern has been found in both countries. The Australian and New Zealand populations were genetically different, and were different from the European and Asian populations. Our Bayesian coalescent analyses, based on a combination of novel and published sequence data from three non-recombinogenic protein-encoding regions, showed that TuMV probably started to migrate from Europe to Australia and New Zealand more than 80 years ago, and that distinct populations arose as a result of evolutionary drivers such as recombination. The basal-B2 subpopulation in Australia and New Zealand seems to be older than those of the world-B2 and -B3 populations. To our knowledge, our study presents the first population genetic analysis of TuMV in Australia and New Zealand. We have shown that the time of migration of TuMV correlates well with the establishment of agriculture and migration of Europeans to these countries.}, } @article {pmid25478544, year = {2014}, author = {Naderi, N and Bakhshandeh, H and Ardeshiri, M and Barzegari, F and Amin, A and Taghavi, S and Maleki, M}, title = {Hyper-Prolactinemia in Men With Idiopathic Dilated Cardiomyopathy: Does It Have any Prognostic Implications?.}, journal = {Research in cardiovascular medicine}, volume = {3}, number = {3}, pages = {e19321}, pmid = {25478544}, issn = {2251-9572}, abstract = {BACKGROUND: Prolactin (PRL) has increasingly been recognized to play a stimulatory role in inflammatory response. Recently, studies have reported an increase in prolactin level among patients with chronic heart failure, however, there is conflicting data about its role as a prognostic factor in these patients.

OBJECTIVES: We aimed to measure PRL level in male patients with idiopathic dilated cardiomyopathy (IDC) and its relationship with some prognostic factors.

PATIENTS AND METHODS: Serum prolactin level was assessed in 33 men with a diagnosis of IDC, left ventricle ejection fraction (LVEF) less than 35% on standard medical therapy for heart failure and New York Heart Association class II-III. Serum NT-Pro BNP (N terminal pro brain natriuretic peptide), hs-CRP (High sensitive C reactive protein) and six-minute walk test (6MWT) were also measured. Our secondary endpoints were mortality, transplantation and hospitalization due to acute heart failure and all patients were followed for one year.

RESULTS: The mean age was 33 ± 7 years (24-45 years) and the mean LVEF was 23% ± 6.5. The mean PRL level was 16 ± 7.7 ng/mL (95% confidence interval: 13.3-18.7 ng/mL), which was significantly higher than normal reference values (4.04-15 ng/mL) (P < 0.0001). There was no correlation between PRL levels and pro BNP, hs-CRP or 6MWT test, however, the serum PRL level was slightly higher among patients who died or were hospitalized or transplanted.

CONCLUSIONS: Considering our study results, prognostic implication of PRL should be questioned. However, it seems that the significant increase in serum PRL in the study population needs more consideration and may have its own pathophysiologic importance. Further studies are recommended for better addressing the role of PRL in chronic heart failure patients.}, } @article {pmid25478233, year = {2014}, author = {Mirmalek, SA and Hajilou, M and Salimi Tabatabaee, SA and Parsa, Y and Yadollah-Damavandi, S and Parsa, T}, title = {Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients.}, journal = {International journal of breast cancer}, volume = {2014}, number = {}, pages = {564308}, pmid = {25478233}, issn = {2090-3170}, abstract = {Prognostic factors are in interest for breast cancer as the second cause of malignancy deaths. Some have predictive values as human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER). To access the incidence of HER2 and its relations to other factors, like age, pathology, ER, progesterone receptor (PR), and P53, 2000 pathologic blocks from 2750 total samples have been selected from 2011 to 2013 in Cancer Institute of Tehran. Incidence of HER2, ER, PR, and P53 was; 58.5%, 33.4%, 43.3%, and 65.4%, respectively. Invasive ductal carcinoma was the most pathologic type (82.2%) and 60%-70% positive HER2 and P53 had negative ER and PR (poor prognosis). The peak age of incidence of breast cancer was perimenopausal age group (46-55 years). Our cases had more positive HER2 and P53 and less positive PR and ER compared to other studies. High perimenopausal incidence as another finding assures the importance of breast cancer screening in these age groups.}, } @article {pmid25477833, year = {2014}, author = {Levit Binnun, N and Tarrasch, R}, title = {Relation between contemplative exercises and an enriched psychology students' experience in a neuroscience course.}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {1296}, pmid = {25477833}, issn = {1664-1078}, abstract = {This article examines the relation of contemplative exercises with enhancement of students' experience during neuroscience studies. Short contemplative exercises inspired by the Buddhist tradition of self-inquiry were introduced in an undergraduate neuroscience course for psychology students. At the start of the class, all students were asked to participate in short "personal brain investigations" relevant to the topic presented. These investigations were aimed at bringing stable awareness to a specific perceptual, emotional, attentional, or cognitive process and observing it in a non-judgmental, non-personal way. In addition, students could choose to participate, for bonus credit, in a longer exercise designed to expand upon the weekly class activity. In the exercise, students continued their "personal brain investigations" for 10 min a day, 4 days a week. They wrote "lab reports" on their daily observations, obtained feedback from the teacher, and at the end of the year reviewed their reports and reflected upon their experiences during the semester. Out of 265 students, 102 students completed the bonus track and their final reflections were analyzed using qualitative methodology. In addition, 91 of the students answered a survey at the end of the course, 43 students participated in a quiz 1 year after course graduation, and the final grades of all students were collected and analyzed. Overall, students reported satisfaction from the exercises and felt they contributed to their learning experience. In the 1-year follow-up, the bonus-track students were significantly more likely than their peers to remember class material. The qualitative analysis of bonus-track students' reports revealed that the bonus-track process elicited positive feelings, helped students connect with class material and provided them with personal insights. In addition, students acquired contemplative skills, such as increased awareness and attention, non-judgmental attitudes, and better stress-management abilities. We provide examples of "personal brain investigations" and discuss limitations of introducing a contemplative approach.}, } @article {pmid25476558, year = {2015}, author = {Singh, TP and Blume, ED and Alexander, PM and Gauvreau, K}, title = {Association of hemodynamic profiles with wait-list mortality in children listed for heart transplantation with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {115}, number = {2}, pages = {243-248}, doi = {10.1016/j.amjcard.2014.10.030}, pmid = {25476558}, issn = {1879-1913}, mesh = {Adolescent ; Cardiomyopathy, Dilated/mortality/physiopathology/*surgery ; Cause of Death/trends ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; *Heart Transplantation ; Humans ; Infant ; Male ; Pulmonary Wedge Pressure/physiology ; Retrospective Studies ; Risk Assessment/*methods ; Risk Factors ; Survival Rate/trends ; Time Factors ; United States/epidemiology ; Waiting Lists/*mortality ; }, abstract = {The prognostic significance of intracardiac hemodynamics in children with advanced heart failure is unknown. The purpose of this study was to describe hemodynamic profiles in children with idiopathic dilated cardiomyopathy (IDC) listed for heart transplant (HT) and to assess their association with wait-list mortality. We identified all US children <18 years with IDC listed for HT during 2000 to 2010 with available pulmonary capillary wedge pressure (PCWP) and cardiac index (CIx) data. We excluded children on ventilator or mechanical support at listing. CIx >2.2 L/min/m(2) (warm) and PCWP >18 mm Hg (wet) were used to define 4 hemodynamic profiles: warm-dry, warm-wet, cold-dry, and cold-wet. The primary end point was death on the wait-list or becoming too sick to transplant. Of 476 children analyzed, 248 (52%) children had PCWP >18 mm Hg and 300 (63%) had CIx >2.2 L/min/m(2). Overall, 36% children were warm-dry, 27% were warm-wet, 12% were cold-dry, and 25% were cold-wet; 32 (6.7%) children reached the primary end point. In adjusted analysis, cold-dry (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.1, 11.5) and cold-wet (HR 3.2, 95% CI 1.2, 8.6) children were at higher risk of wait-list death versus warm-dry children, whereas warm-wet children were not (HR 2.3, 95% CI 0.8, 6.6). All groups were equally likely to receive HT and had similar 1-year post-transplant survival. In conclusion, in children with IDC listed for HT, those with low cardiac output at evaluation are at higher risk of wait-list mortality. Defining hemodynamic profiles may improve risk stratification of children with IDC listed for HT.}, } @article {pmid25476465, year = {2015}, author = {Ando, M and Shimizu, Y and Sano, T and Senda, Y and Nimura, Y and Yamao, K and Nagino, M and Yanagisawa, A}, title = {Poor prognosis of common-type invasive ductal carcinomas that originate in the branching pancreatic duct.}, journal = {Surgery today}, volume = {45}, number = {10}, pages = {1291-1298}, pmid = {25476465}, issn = {1436-2813}, mesh = {Aged ; *Carcinoma, Pancreatic Ductal/classification/mortality/pathology ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; *Pancreatic Ducts ; *Pancreatic Neoplasms/classification/mortality/pathology ; Prognosis ; Survival Rate ; }, abstract = {PURPOSE: To clarify the incidence, clinicopathological features and prognosis of pancreatic invasive ductal carcinomas (IDCs) with different tumor origin sites in the pancreatic duct.

METHODS: Based on the relationship between the invasive cancer area (ICA) and the main pancreatic duct (MPD), IDCs less than 2 cm in diameter were classified into two groups: type I, in which the ICA and MPD were separated, and type II, in which the MPD passed through the ICA. The clinicopathological findings and prognosis of each type were compared in a total of 37 patients.

RESULTS: The incidences of IDC types I and II were 18.9 and 81.1 %, respectively. Although there was no difference in local invasion, both node involvement and venous invasion tended to occur more frequently in type I IDC, and the three-year survival rate was significantly lower for type I (28.6 %) than type II (71.8 %) IDC.

CONCLUSIONS: The prognosis of IDCs that originated in the branching pancreatic duct (BPD) distant from the MPD (type I) was worse than the prognosis of IDCs that originated in either the MPD or the BPD close to the MPD (type II). These data suggest that the progression and degree of malignancy of IDCs may vary depending on the site of tumor origin in the pancreatic duct.}, } @article {pmid25470484, year = {2014}, author = {Scalone, L and Cesana, G and Furneri, G and Ciampichini, R and Beck-Peccoz, P and Chiodini, V and Mangioni, S and Orsi, E and Fornari, C and Mantovani, LG}, title = {Burden of diabetes mellitus estimated with a longitudinal population-based study using administrative databases.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e113741}, pmid = {25470484}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Databases, Factual ; Diabetes Complications/*economics/*epidemiology ; Diabetes Mellitus, Type 2/*economics/*epidemiology ; Female ; Health Care Costs ; Humans ; Infant ; Infant, Newborn ; Insurance Claim Review/economics ; Italy/epidemiology ; Longitudinal Studies ; Male ; Middle Aged ; Young Adult ; }, abstract = {OBJECTIVE: To assess the epidemiologic and economic burden of diabetes mellitus (DM) from a longitudinal population-based study.

RESEARCH DESIGN AND METHODS: Lombardy Region includes 9.9 million individuals. Its DM population was identified through a data warehouse (DENALI), which matches with a probabilistic linkage demographic, clinical and economic data of different Healthcare Administrative databases. All individuals, who, during the year 2000 had an hospital discharge with a IDC-9 CM code 250.XX, and/or two consecutive prescriptions of drugs for diabetes (ATC code A10XXXX) within one year, and/or an exemption from co-payment healthcare costs specific for DM, were selected and followed up to 9 years. We calculated prevalence, mortality and healthcare costs (hospitalizations, drugs and outpatient examinations/visits) from the National Health Service's perspective.

RESULTS: We identified 312,223 eligible subjects. The study population (51% male) had a mean age of 66 (from 0.03 to 105.12) years at the index date. Prevalence ranged from 0.4% among subjects aged ≤45 years to 10.1% among those >85 years old. Overall 43.4 deaths per 1,000 patients per year were estimated, significantly (p<0.001) higher in men than women. Overall, 3,315€/patient-year were spent on average: hospitalizations were the cost driver (54.2% of total cost). Drugs contributed to 31.5%, outpatient claims represented 14.3% of total costs. Thirty-five percent of hospital costs were attributable to cerebro-/cardiovascular reasons, 6% to other complications of DM, and 4% to DM as a main diagnosis. Cardiovascular drugs contributed to 33.5% of total drug costs, 21.8% was attributable to class A (16.7% to class A10) and 4.3% to class B (2.4% to class B01) drugs.

CONCLUSIONS: Merging different administrative databases can provide with many data from large populations observed for long time periods. DENALI shows to be an efficient instrument to obtain accurate estimates of burden of diseases such as diabetes mellitus.}, } @article {pmid25466398, year = {2015}, author = {Alberti, N and Bechade, D and Dupuis, F and Crombe, A and Neuville, A and Debled, M and Palussiere, J and Buy, X and Perez, JT and Desjardin, M and Frulio, N and Kind, M}, title = {Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: report of five cases.}, journal = {Diagnostic and interventional imaging}, volume = {96}, number = {1}, pages = {73-78}, doi = {10.1016/j.diii.2014.11.003}, pmid = {25466398}, issn = {2211-5684}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Female ; Humans ; Liver Neoplasms/*pathology/*secondary ; Middle Aged ; }, abstract = {BACKGROUNDS AND AIMS: Hepar lobatum carcinomatosum (HLC) is an exceptional acquired hepatic distortion which consists in irregularly lobulated hepatic contours seen in patients with known liver metastases, usually from breast carcinoma. We aimed to describe and analyze five similar cases of HLC resulting from metastatic mammary carcinoma in the liver and associated with rapid hepatic failure.

METHODS: Five cases of HLC were investigated. Medical (including blood liver tests), radiological and histological data (2 cases) were collected and retrospectively analyzed. All patients were followed up for metastatic invasive ductal carcinoma of the breast and had a common pattern of treatment with combination of targeted therapies (bevacizumab, AVASTIN) and chemotherapy (paclitaxel, TAXOL).

RESULTS: All the patients showed rapid hepatic failure after a mean of 9 courses of bevacizumab/paclitaxel. In all cases, liver imaging revealed liver capsule retraction and an irregular lobular margin. An apparent tumor regression of all liver metastases was showed in two cases. Biopsies were consistent with sinusoidal obstruction syndrome (SOS) and, surprisingly, no tumoral cells were found.

CONCLUSION: Although rare, such an unusual pattern of liver metastasis may mimick acute cirrhosis and cause rapid hepatic failure in patients, despite possible apparent tumor regression on imaging. The etiology of this pathology is unclear, and may involve multiple pathogenic factors. Direct or indirect vascular injury plays an important role in the development of HLC.}, } @article {pmid25465281, year = {2015}, author = {Encinas-Vicente, A and Prim-Espada, MP and Cenjor-Español, C and de Diego-Sastre, JI}, title = {Impact of Otolaryngology theses in their authors' scientific production.}, journal = {Acta otorrinolaringologica espanola}, volume = {66}, number = {5}, pages = {269-274}, doi = {10.1016/j.otorri.2014.09.008}, pmid = {25465281}, issn = {1988-3013}, mesh = {*Academic Dissertations as Topic ; Authorship ; *Bibliometrics ; Efficiency ; Follow-Up Studies ; Humans ; *Otolaryngology ; Periodicals as Topic/statistics & numerical data ; Publishing ; Research ; Spain ; }, abstract = {INTRODUCTION AND OBJECTIVES: The writing of a thesis has 2 main objectives: the appropriate training to be a good researcher and the publication of the first original research work. This study attempted to check this statement applied to theses in Otolaryngology by analysing the variation in the authors' publications.

MATERIAL AND METHODS: We used the database TESEO to obtain the data relative to Otolaryngology theses in Spain published between 1993 and 2003. We found the publications of each author by using de programme "Publish or Perish" and we analysed the variations in their work in 3 periods (prior to, around and after thesis publication).

RESULTS: The publications, the citations and the parameters analysed all increased in the second and third periods (around and after) with regard to the first period. However, there were no significant differences in some of them in the first 2 periods.

CONCLUSIONS: The elaboration of a thesis in Otolaryngology increased the scientific production of its author. Almost a third of the authors did not publish any work. There was a significant increase in all the parameters studied and the bibliometric indices between the period before thesis publication and the around and after thesis periods.}, } @article {pmid25463136, year = {2014}, author = {Tibon, R and Gronau, N and Scheuplein, AL and Mecklinger, A and Levy, DA}, title = {Associative recognition processes are modulated by the semantic unitizability of memoranda.}, journal = {Brain and cognition}, volume = {92C}, number = {}, pages = {19-31}, doi = {10.1016/j.bandc.2014.09.009}, pmid = {25463136}, issn = {1090-2147}, abstract = {Although memory of episodic associations is generally considered to be recollective in nature, it has been suggested that when stimuli are experienced as a unit, familiarity processes might contribute to their subsequent associative recognition. To investigate the effect of semantic relatedness during episodic encoding on the processes of retrieval of associative information, we had participants interactively encode pairs of object pictures, vertically arranged so as to suggest a functional or configural relationship between them. Half the pairs were independently judged to be of related objects (e.g., a lamp over a table) and half of unrelated objects (e.g., a key-ring over an apple). At test, participants discriminated between intact, recombined, and new pairs while event related potentials (ERPs) were recorded. In an early ERP marker of retrieval success generally associated with familiarity processes, differences related to associative memory only emerged for related pairs, while differences associated with item memory emerged for both related and unrelated pairs. In contrast, in a later ERP effect associated with recollection, differences related to associative memory emerged for both related and unrelated pairs. These findings may indicate that retrieval of episodic associations formed between two semantically related visual stimuli can be supported by familiarity-related processes.}, } @article {pmid25462782, year = {2015}, author = {Greenwald, MJ and Redding, AM and Cannon, FS}, title = {A rapid kinetic dye test to predict the adsorption of 2-methylisoborneol onto granular activated carbons and to identify the influence of pore volume distributions.}, journal = {Water research}, volume = {68}, number = {}, pages = {784-792}, doi = {10.1016/j.watres.2014.10.022}, pmid = {25462782}, issn = {1879-2448}, mesh = {Adsorption ; Camphanes/*chemistry ; Carbon/chemistry ; Charcoal/*chemistry ; Coal ; Cocos/chemistry ; Diffusion ; Fluorescent Dyes/chemistry ; Hydrogen-Ion Concentration ; Kinetics ; Methylene Blue/chemistry ; Models, Theoretical ; Particle Size ; Phenols/*chemistry ; Porosity ; Reproducibility of Results ; Sulfoxides/*chemistry ; Time Factors ; Water Pollutants, Chemical/*chemistry ; Water Purification/instrumentation/methods ; }, abstract = {The authors have developed a kinetic dye test protocol that aims to predict the competitive adsorption of 2-methylisoborneol (MIB) to granular activated carbons (GACs). The kinetic dye test takes about two hours to perform, and produces a quantitative result, fitted to a model to yield an Intraparticle Diffusion Constant (IDC) during the earlier times of dye sorption. The dye xylenol orange was probed into six coconut-based GACs and five bituminous-based GACs that hosted varied pore distributions. Correlations between xylenol orange IDCs and breakthrough of MIB at 4 ppt in rapid small-scale column tests (RSSCTs) were found with R[2]s of 0.85 and 0.95 for coconut carbons that processed waters with total organic carbon (TOCs) of 1.9 and 2.2 ppm, respectively, and with an R[2] of 0.94 for bituminous carbons that processed waters with a TOC of 2.5 ppm. The author sought to study the influence of the pore sizes, which provide the adsorption sites and the diffusion conduits that are necessary for the removal of those compounds. For coconut carbons, a linear correlation was established between the xylenol orange IDCs and the volume of pores in the range of 23.4-31.8 Å widths (R[2] = 0.98). For bituminous carbons, best correlation was to pores ranging from 74 to 93 Å widths (R[2] = 0.94). The differences in adsorption between coconut carbons and bituminous carbons have been attributed to the inherently dissimilar graphene layering resulting from the parent materials and the activation processes. When fluorescein dye was employed in the kinetic dye tests, the correlations to RSSCT-MIB performance were not as high as when xylenol orange was used. Intriguingly, it was the same pore size ranges that exhibited the strongest correlation for MIB RSSCT's, xylenol orange kinetics, and fluoroscein kinetics. When methylene blue dye was used, sorption occurred so rapidly as to be out of the scope of the IDC model.}, } @article {pmid25461433, year = {2015}, author = {Seifert, L and Schnitzler, C and Bideault, G and Alberty, M and Chollet, D and Toussaint, HM}, title = {Relationships between coordination, active drag and propelling efficiency in crawl.}, journal = {Human movement science}, volume = {39}, number = {}, pages = {55-64}, doi = {10.1016/j.humov.2014.10.009}, pmid = {25461433}, issn = {1872-7646}, mesh = {Adult ; Algorithms ; Biomechanical Phenomena ; Body Size ; Humans ; Male ; Movement ; Regression Analysis ; *Swimming ; Video Recording ; Water ; Young Adult ; }, abstract = {This study examines the relationships between the index of coordination (IdC) and active drag (D) assuming that at constant average speed, average drag equals average propulsion. The relationship between IdC and propulsive efficiency (ep) was also investigated at maximal speed. Twenty national swimmers completed two incremental speed tests swimming front crawl with arms only in free condition and using a measurement of active drag system. Each test was composed of eight 25-m bouts from 60% to 100% of maximal intensity whereby each lap was swum at constant speed. Different regression models were tested to analyse IdC-D relationship. Correlation between IdC and ep was calculated. IdC was linked to D by linear regression (IdC=0.246·D-27.06; R(2)=0.88, P<.05); swimmers switched from catch-up to superposition coordination mode at a speed of ∼1.55ms(-1) where average D is ∼110N. No correlation between IdC and ep at maximal speed was found. The intra-individual analysis revealed that coordination plays an important role in scaling propulsive forces with higher speed levels such that these are adapted to aquatic resistance. Inter-individual analysis showed that high IdC did not relate to a high ep suggesting an individual optimization of force and power generation is at play to reach high speeds.}, } @article {pmid25459069, year = {2015}, author = {Yu, JI and Choi, DH and Huh, SJ and Ahn, SJ and Lee, JS and Shin, KH and Kwon, Y and Kim, YB and Suh, CO and Kim, JH and Cho, J and Kim, IA and Lee, JH and Park, W}, title = {Unique characteristics and failure patterns of metaplastic breast cancer in contrast to invasive ductal carcinoma: a retrospective multicenter case-control study (KROG 13-07).}, journal = {Clinical breast cancer}, volume = {15}, number = {2}, pages = {e105-15}, doi = {10.1016/j.clbc.2014.10.002}, pmid = {25459069}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local/*mortality ; Prognosis ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/mortality/*pathology ; Young Adult ; }, abstract = {BACKGROUND: This retrospective study was performed to investigate the need for management modification in MBC according to evaluation of characteristics and failure patterns compared with IDC.

PATIENTS AND METHODS: We performed this multicenter study taking MBC and randomly assigned IDC cases matched for age (± 3 years), pathologic stage (T and N), locoregional treatment methods (surgery with or without radiation therapy), and period of treatment (± 6 months) that occurred from January 1999 to November 2011 in the 6 institutions of the Korean Radiation Oncology Group.

RESULTS: A total of 144 female MBC patients were enrolled. The median follow-up was 51 months (range, 1-186 months). The rates of positivity for estrogen receptor (P < .001), progesterone receptor (P < .001), and HER2 (P = .007) were significantly lower in MBC patients. During follow-up, recurrence developed in 22 (15.3%) MBC and 6 (4.2%) IDC patients (P = .002). The median time to recurrence of MBC and IDC was 15 months and 24 months, respectively. Most instances of recurrence in MBC developed in the triple-negative (TN) subgroup (TN-MBC). In particular, locoregional recurrence developed exclusively in the TN-MBC subgroup. In the TN-MBC subgroup, the number of risk factors (pT2-3, N1-3) was related to significant differences in overall survival (P = .001) and recurrence-free survival (P < .001).

CONCLUSION: The MBC patients had a higher rate of TN, poorer differentiation, and a higher recurrence rate than did the IDC patients. Considering the unique characteristics and failure patterns, it is necessary to modify the current management guidelines for MBC.}, } @article {pmid25457635, year = {2014}, author = {Xia, HJ and He, BL and Wang, CY and Zhang, HL and Ge, GZ and Zhang, YX and Lv, LB and Jiao, JL and Chen, C}, title = {PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {18}, pages = {3230-3242}, doi = {10.1016/j.ejca.2014.10.012}, pmid = {25457635}, issn = {1879-0852}, mesh = {9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinogens ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Papillary/genetics ; *Disease Models, Animal ; Estrogens/metabolism ; Female ; Mammary Glands, Animal/metabolism ; Mammary Neoplasms, Animal/chemically induced/*genetics ; Mammary Neoplasms, Experimental/chemically induced/*genetics ; Medroxyprogesterone Acetate ; Mutation/*genetics ; PTEN Phosphohydrolase/*genetics ; Papilloma, Intraductal/genetics ; Phosphatidylinositol 3-Kinase/*genetics ; Progesterone/metabolism ; Random Allocation ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tupaiidae ; }, abstract = {Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.}, } @article {pmid25456102, year = {2014}, author = {Ouldamer, L and Lechaux, E and Arbion, F and Body, G and Vildé, A}, title = {What should be the width of radiological margin to optimize resection of non-palpable invasive or in situ ductal carcinoma?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {6}, pages = {889-893}, doi = {10.1016/j.breast.2014.10.001}, pmid = {25456102}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*surgery ; Female ; Humans ; Mammography ; Middle Aged ; Neoplasm, Residual ; Retrospective Studies ; Surgery, Computer-Assisted/*methods ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: the aim of our study was to investigate whether there is radiological margin that optimize resection of non-palpable invasive or in situ ductal carcinoma.

MATERIALS AND METHODS: Data were collected for all patients undergoing wire localization prior to therapeutic surgical excision between January 2010 and December 2013 at our institution. A 5 and 10-mm radiological margins were considered adequate for invasive ductal carcinoma (IDC) and in situ ductal carcinoma (DCIS) respectively. Clear histological margins were defined as no ink on the tumor for IDC and ≥2 mm for DCIS. Data were analyzed both in order to assess accuracy of the technique and in order to determine what radiological threshold should be taken.

RESULTS: Three hundred seventy seven women were included to the study. The radiological thresholds permitted negative histological margins in 94.7%, 60.9% and 80.9% in the pure invasive ductal carcinoma group (IDC, n = 133), the pure ductal carcinoma in situ group (DCIS, n = 92) and the mixed group (both IDC and DCIS, n = 152) respectively. In an ROC analysis evaluating the ability of radiological thresholds to obtain free pathological margins: the AUC was 0.79 (0.71-0.87, 95% confident interval, p = .0007) for Pure IDC group, 0.67 (0.57-0.87, 95% confident interval, p = .0005) for pure DCIS group, and 0.72 (0.62-0.80, 95% confident interval, p < .0001) for the mixed group.

CONCLUSION: We found that a radiological margin of 10 mm is needed in presence of an in situ component and 5-mm radiological margin seems enough in case of pure IDC tumors.}, } @article {pmid25455606, year = {2014}, author = {Bozorgmehr, M and Moazzeni, SM and Salehnia, M and Sheikhian, A and Nikoo, S and Zarnani, AH}, title = {Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells.}, journal = {Immunology letters}, volume = {162}, number = {2 Pt B}, pages = {239-246}, doi = {10.1016/j.imlet.2014.10.005}, pmid = {25455606}, issn = {1879-0542}, mesh = {Adult ; Antigens, Differentiation/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Female ; Humans ; Interleukin-10/immunology ; Interleukin-6/immunology ; *Menstruation ; Mesenchymal Stem Cells/cytology/*immunology ; Monocytes/cytology/*immunology ; }, abstract = {INTRODUCTION: Menstrual blood stromal stem Cells (MenSCs) have shown promising potential for future clinical settings. Nonetheless, data regarding their interaction with immune cells is still scarce. Here, we investigated whether MenSCs could affect the generation and/or maturation of human blood monocyte-derived dendritic cells (DCs).

MATERIALS AND METHODS: MenSCs were isolated from menstrual blood of normal women through culture of adherent mononuclear cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) in the presence or absence of MenSCs. Monocyte-derived cells were assessed for the percentage of monocyte-, iDC-, and mDC-specific markers as well as the expression of costimulatory molecules. IL-6 and IL-10 levels were also determined in supernatants of MenSC-monocytes cocultures.

RESULTS: Optimal phenotypic differentiation of monocytes into iDCs was inhibited upon coculture with MenSCs. Moreover, higher levels of IL-6 and IL-10 were detected in these settings. Even though addition of MenSCs to iDC cultures could not prevent iDC maturation, coculture of MenSCs with monocytes from the beginning of differentiation process could effectively hinder generation of fully mature DCs.

CONCLUSION: This is the first study to address the inhibitory impact of MenSCs on generation and maturation of DCs. IL-6 and IL-10 could be partly held responsible for this effect. Given the central roles of DCs in regulation of immune responses, these results highlight the importance of further research on the potential modulatory impacts of MenSCs, as rather easily accessible and expandable stem cells, on the immune system-related cells.}, } @article {pmid25455303, year = {2014}, author = {Raimo, S and Trojano, L and Spitaleri, D and Petretta, V and Grossi, D and Santangelo, G}, title = {Apathy in multiple sclerosis: a validation study of the apathy evaluation scale.}, journal = {Journal of the neurological sciences}, volume = {347}, number = {1-2}, pages = {295-300}, doi = {10.1016/j.jns.2014.10.027}, pmid = {25455303}, issn = {1878-5883}, mesh = {Adult ; *Apathy ; *Cognition ; Disability Evaluation ; *Executive Function ; Female ; Humans ; Male ; Middle Aged ; Motivation ; Multiple Sclerosis/*psychology ; Neuropsychological Tests/standards ; Psychiatric Status Rating Scales/*standards ; Psychometrics/*methods/statistics & numerical data ; Reproducibility of Results ; Young Adult ; }, abstract = {BACKGROUND: Apathy is defined as lack of motivation affecting cognitive, emotional, and behavioral domains and is usually assessed by standardized scales, such as the Apathy Evaluation Scale (AES). Recently, apathy has been recognized as a frequent behavioral symptom in multiple sclerosis (MS).

OBJECTIVE: To evaluate applicability and clinical-metric properties of AES in MS and the agreement between patients' and caregivers' evaluation of apathy.

MATERIALS AND METHODS: Seventy non-demented MS patients underwent a thorough clinical and neuropsychological assessment, including evaluation of apathy according to established clinical criteria. All patients also completed the self-report version of AES (AES-S).

RESULTS: AES-S was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha, α=0.87). The factorial analysis identified three factors, representing the cognitive dimension (α=0.87), a general aspect of apathy (α=0.84), and the behavioral-emotional aspects (α=0.74), respectively. The factors were significantly correlated with the total AES score (all rrho≥0.73, p<0.001). The total AES score showed fair convergent validity (rrho=0.38) and discriminant validity when compared to Expanded Disability Status Scale (rrho=0.38), Mini Mental State Examination (rrho=-0.17), and Hamilton Depression Rating Scale (rrho=0.37). Receiver-operating characteristic curve analysis demonstrated that a cutoff>35.5 can identify clinically significant apathy with good sensitivity (88%) and specificity (72%); such a cutoff identified apathy in 35.7% of our sample of non-demented MS patients. Total AES score was significantly correlated with reduced global cognitive efficiency and more severe frontal executive dysfunctions.

CONCLUSION: AES-S can be considered as an easy and reliable tool to assess apathy in non-demented MS. The use of AES-S in non-demented MS patients is clinically important since apathy is relatively frequent and is correlated to more severe cognitive dysfunction.}, } @article {pmid25453949, year = {2015}, author = {Marelli, B and Ghezzi, CE and James-Bhasin, M and Nazhat, SN}, title = {Fabrication of injectable, cellular, anisotropic collagen tissue equivalents with modular fibrillar densities.}, journal = {Biomaterials}, volume = {37}, number = {}, pages = {183-193}, doi = {10.1016/j.biomaterials.2014.10.019}, pmid = {25453949}, issn = {1878-5905}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Anisotropy ; Biocompatible Materials/pharmacology ; Cell Transdifferentiation/drug effects ; Cells, Cultured ; Collagen/*pharmacology ; Fibroblasts/*cytology/drug effects/ultrastructure ; Gels ; Gene Expression Regulation/drug effects ; Injections ; Mesenchymal Stem Cells/cytology/drug effects/metabolism/ultrastructure ; Mice ; NIH 3T3 Cells ; Nanoparticles/ultrastructure ; Neurons/cytology/drug effects ; Osteoblasts/*cytology/drug effects/metabolism ; Osteogenesis/drug effects ; Rats ; }, abstract = {Technological improvements in collagen gel fabrication are highly desirable as they may enable significant advances in the formation of tissue-equivalent biomaterials for regenerative medicine, three-dimensional (3D) in vitro tissue models, and injectable scaffolds for cell and drug delivery applications. Thus, strategies to modulate collagen gel fibrillar density and organization in the mesostructure have been pursued to fabricate collagenous matrices with extracellular matrix-like features. Herein, we introduce a robust and simple method, namely gel aspiration-ejection (GAE), to engineer 3D, anisotropic, cell seeded, injectable dense collagen (I-DC) gels with controllable fibrillar densities, without the use of crosslinking. GAE allows for the hybridization of collagen gels with bioactive agents for increased functionality and supports highly aligned homogenous cell seeding, thus providing I-DC gels with distinct properties when compared to isotropic DC gels of random fibrillar orientation. The hybridization of I-DC with anionic fibroin derived polypeptides resulted in the nucleation of carbonated hydroxyapatite within the aligned nanofibrillar network upon exposure to simulated body fluid, yielding a 3D, anisotropic, mineralized collagen matrix. In addition, I-DC gels accelerated the osteoblastic differentiation of seeded murine mesenchymal stem cells (m-MSCs) when exposed to osteogenic supplements, which resulted in the cell-mediated, bulk mineralization of the osteoid-like gels. In addition, and upon exposure to neuronal transdifferentiation medium, I-DC gels supported and accelerated the differentiation of m-MSCs toward neuronal cells. In conclusion, collagen GAE presents interesting opportunities in a number of fields spanning tissue engineering and regenerative medicine to drug and cell delivery.}, } @article {pmid25449295, year = {2015}, author = {Cabello-Benavente, R and González-Enguita, C}, title = {Residency in urology and training in kidney transplantation. Results of a national survey.}, journal = {Actas urologicas espanolas}, volume = {39}, number = {5}, pages = {303-309}, doi = {10.1016/j.acuro.2014.09.002}, pmid = {25449295}, issn = {1699-7980}, mesh = {Academic Medical Centers ; Attitude of Health Personnel ; Curriculum ; Humans ; Internet ; Internship and Residency/*statistics & numerical data ; Kidney Transplantation/*education/statistics & numerical data ; Laparoscopy/education ; Personal Satisfaction ; Physicians/*psychology ; Spain ; Surveys and Questionnaires ; Urology/*education ; }, abstract = {OBJECTIVES: To determine the current state of kidney transplantation (KT) training in a country that is leader in organ donation and transplantation.

MATERIAL AND METHODS: We conducted an online survey by e-mail to 138 urology residents. The survey contained 5 sections: affiliation, training in KT, interest in KT, residents of transplant centers and residents of nontransplant centers.

RESULTS: Sixty-five residents responded, 47.1% of the urologists in training surveyed, representing 28 cities and 15 provinces. Fifty-five percent (n=36) of the respondents deemed the KT training offered during their residency as insufficient, and 85% (n=55) demanded more resources. More than half were not confident in their abilities to perform transplantation surgery over the course of their residency (n=35). Nineteen percent of the residents considered KT an important discipline in their residency, with a mean score of 56.2 (1-100). Among the residents of the transplant centers (69.2%, n=45), 73% (n=33) considered KT when choosing a center for their residency. Of the surveyed residents from nontransplant centers (30.7%, n=20), 45% (n=9) do not perform an external rotation in KT.

CONCLUSIONS: The surveyed residents demand more training in KT. The most common situation is to end a residency without having performed a complete KT. KT is considered an asset when selecting a resident medical intern position and commonly they are part of the transplantation team. The majority of residents are trained in centers with less than 75 transplants/year. External rotations in KT are not the rule in centers where transplantation is not performed.}, } @article {pmid25445919, year = {2015}, author = {Wahler, J and So, JY and Cheng, LC and Maehr, H and Uskokovic, M and Suh, N}, title = {Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {148}, number = {}, pages = {148-155}, pmid = {25445919}, issn = {1879-1220}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; R03CA172827/CA/NCI NIH HHS/United States ; K22CA133105/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/drug effects ; Biomarkers, Tumor/genetics/*metabolism ; Blotting, Western ; Breast/*drug effects/metabolism/pathology ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Humans ; Neoplastic Stem Cells/*drug effects/metabolism/pathology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured ; Vitamin D/*pharmacology ; Vitamins/*pharmacology ; }, abstract = {Breast cancer stem cells (BCSCs) are a subset of tumor cells that are believed to be the cells responsible for the establishment and maintenance of tumors. Moreover, BCSCs are suggested to be the main cause of progression to metastasis and recurrence of cancer because of their tumor-initiating abilities and resistance to conventional therapies. Ductal carcinoma in situ (DCIS) is an early precursor in breast carcinogenesis which progresses to invasive ductal carcinoma (IDC). We have previously reported that a vitamin D compound, BXL0124, inhibits the progression of DCIS to IDC. In the present study we sought to determine whether this effect was mediated through an influence on BCSCs. In MCF10DCIS cells treated with vitamin D compounds (1α25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44(+)/CD24(-/low) and CD49f(+)/CD24(-/low) subpopulations, was reduced. To determine the effects of vitamin D compounds on cancer stem cell activity, the MCF10DCIS mammosphere cell culture system, which enriches for mammary progenitor cells and putative BCSCs, was utilized. Untreated MCF10DCIS mammospheres showed a disorganized and irregular shape. When MCF10DCIS cells were treated with 1α25(OH)2D3 or BXL0124, the mammospheres that formed exhibited a more organized, symmetrical and circular shape, similar to the appearance of spheres formed by the non-malignant, normal mammary epithelial cell line, MCF10A. The mammosphere forming efficiency (MFE) was significantly decreased upon treatment with 1α25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1α25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFκB. Furthermore, 1α25(OH)2D3 and BXL0124 reduced the expression of pluripotency markers, OCT4 and KLF-4 in mammospheres. This study suggests that vitamin D compounds repress the breast cancer stem cell-like population, potentially contributing to their inhibition of breast cancer. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.}, } @article {pmid25445503, year = {2014}, author = {Xu, X and Tang, X and Lu, M and Tang, Q and Zhang, H and Zhu, H and Xu, N and Zhang, D and Xiong, L and Mao, Y and Zhu, J}, title = {Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer.}, journal = {Experimental and molecular pathology}, volume = {97}, number = {3}, pages = {579-584}, doi = {10.1016/j.yexmp.2014.11.001}, pmid = {25445503}, issn = {1096-0945}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*biosynthesis ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Up-Regulation ; }, abstract = {Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen (CTA) family, which is one of the largest groups of human tumor-associated antigens. MAGE-A9 is a particular member in the context of the MAGE-A gene family and was defined as presenting prognostic relevance in certain type of human cancer. However, the expression of MAGE-A9 in invasive ductal breast cancer (IDC) and the relationship with the clinical attributes of IDC, especially prognostic characteristic, remain poorly understood. In this present study, one-step quantitative reverse transcription polymerase chain reaction (18 fresh-frozen IDC tissues and corresponding non-cancerous tissues) and immunohistochemistry by tissue microarrays (82 IDC tissue samples and 70 matched tumor-adjacent non-cancerous tissue samples) were performed to characterize expression of the MAGE-A9 gene in IDC. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. The results of qPCR and IHC analysis showed that the expression of MAGE-A9 in IDC was significantly higher than that in corresponding non-cancerous tissue. Moreover, the expression level of MAGE-A9 protein in IDC was significantly related to histological grade (p = 0.011) and distant metastasis (p = 0.019). Multivariate analysis with the Cox regression model showed that MAGE-A9 protein expression (p = 0.009), histological grade (p = 0.014), lymph node metastasis (p = 0.012) and distant metastasis (p = 0.011) were independent prognostic factors for overall survival of IDC patients. The data suggest that MAGE-A9 expression is correlated with malignant attributes of IDC and it may serve as a novel prognostic factor and an ideal candidate for targeted therapy in IDC treatment.}, } @article {pmid25441933, year = {2015}, author = {Sharma, SD and Barry, M and O'Reilly, EA and Kell, MR}, title = {Surgical management of lobular carcinoma from a national screening program: a retrospective analysis.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {41}, number = {1}, pages = {79-85}, doi = {10.1016/j.ejso.2014.09.004}, pmid = {25441933}, issn = {1532-2157}, mesh = {Aged ; Breast/*pathology ; Breast Neoplasms/diagnosis/metabolism/*surgery ; Carcinoma, Ductal, Breast/diagnosis/metabolism/*surgery ; Carcinoma, Lobular/diagnosis/metabolism/*surgery ; Early Detection of Cancer/methods ; Female ; Humans ; Ireland ; Mammography/methods ; Mastectomy/methods ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; Tumor Burden ; }, abstract = {OBJECTIVE: To compare the surgical outcomes of women diagnosed with invasive ductal and lobular carcinoma of the breast.

BACKGROUND: The role of Breast Conserving Surgery (BCS) for invasive cancers of the breast is well established; however its role for invasive lobular carcinoma is less well defined. Concerns exist regarding the need for re-excision of margins and the eventual need for mastectomy in women with Invasive Lobular Carcinoma (ILC) compared with Ductal Carcinoma (IDC). In this study we compare the surgical results of these two groups examining BCS from a national breast cancer screening program.

METHODS: Analysis of mammographically detected ILC and IDC tumours obtained from the national breast cancer screening program of the Republic of Ireland (BreastCheck) was performed. BreastCheck offers biannual screening mammograms to women throughout the Republic of Ireland between 50 and 65 years of age. We examined and pooled the data across 4 screening zones from 2005 to 2010.

CONCLUSIONS: We observed similar success rates and trends in both the ILC and IDC groups where BCS was attempted. Patients selected for BCS with ILC were statistically more likely to have successful surgery compared with IDC as tumour size increased. There however was no statistical difference in a pooled analysis of successful treatment across all tumour sizes in comparing the two groups. We conclude that BCS is an appropriate and acceptable treatment option for women diagnosed with ILC.}, } @article {pmid25435991, year = {2015}, author = {Liu, L and Shi, J and Mao, F and Wei, J and Fu, D and Zhang, J}, title = {Synchronous primary cancers of the thyroid and breast: A case report and review of the literature.}, journal = {Oncology letters}, volume = {9}, number = {1}, pages = {351-354}, pmid = {25435991}, issn = {1792-1074}, abstract = {The current report presents the case of a 41-year-old female exhibiting synchronous primary cancers of the thyroid and breast. Pathological examination of a tissue sample following biopsy identified papillary carcinoma of the thyroid and invasive ductal carcinoma of the breast to provide a definitive diagnosis of synchronous primary tumors. The patient underwent a modified radical mastectomy and total thyroidectomy. Following regular adjuvant chemotherapy with cyclophosphamide (800 mg), doxorubicin (100 mg) and paclitaxel (120 mg), once every three weeks for 3.5 months, oral levothyroxine and endocrinotherapy was recommended. Two years after the initial diagnosis, the patient was healthy with no disease recurrence. To the best of our knowledge, no association has been identified between the etiology and diagnoses of the two synchronous primary tumors. Thus, the aim of the current report was to improve the understanding of synchronous primary tumors of the thyroid and breast by presenting a review of the associated literature regarding breast and thyroid cancer. The mechanisms of synchronous neoplasms have only recently been elucidated, however, misdiagnosis is common. Clinicians are, therefore, advised to carefully examine patients with thyroid or breast cancer to avoid an incorrect or misdiagnosis. Furthermore, the present report aims to provide a reference for the cancer database, since the majority of analyses of rare diseases are derived from case reports. To improve the understanding of synchronous primary cancers of the thyroid and breast, an analysis of recent studies regarding the underlying mechanisms of synchronous primary cancers was also undertaken.}, } @article {pmid25435905, year = {2014}, author = {Gupta, P and Dhingra, S and Musa, O and Srivastava, A}, title = {lnvasive cystic hypersecretory carcinoma of the breast associated with papillary pattern: a rare and poorly recognised variant of ductal carcinoma of the breast.}, journal = {Ecancermedicalscience}, volume = {8}, number = {}, pages = {477}, pmid = {25435905}, issn = {1754-6605}, abstract = {Cystic hypersecretory pattern is a rare and poorly recognised variant of invasive ductal carcinoma of the breast. Cystic hypersecretory lesions of the breast have a spectrum of morphological features ranging from clearly benign cystic hypersecretory hyperplasia (CHH), CHH with atypia, cystic hypersecretory carcinoma (CHC) to invasive CHC. Until now, no case of invasive CHC has been reported in India, to the best of our knowledge. We report a case of a 57-year-old female with a history of a lump in the inferomedial quadrant of the right breast for three years, gradually increasing in size. A mammography showed a well-defined, lobulated radio-opacity. A modified radical mastectomy was done. Gross examination showed multiple cystic spaces filled with thick gelatinous material and solid areas. On histopathology, cystic hypersecretory variant of invasive ductal breast carcinoma with focal papillary pattern was diagnosed. Cystic hypersecretory ductal carcinoma behaves in a low-grade fashion for many years but has a potential for invasiveness and metastasis, so regular follow-up of such cases is crucial.}, } @article {pmid25433206, year = {2015}, author = {Huang, B and Warner, M and Gustafsson, JÅ}, title = {Estrogen receptors in breast carcinogenesis and endocrine therapy.}, journal = {Molecular and cellular endocrinology}, volume = {418 Pt 3}, number = {}, pages = {240-244}, doi = {10.1016/j.mce.2014.11.015}, pmid = {25433206}, issn = {1872-8057}, mesh = {Breast Neoplasms/*drug therapy/metabolism/pathology ; Drug Resistance, Neoplasm ; Estrogen Receptor alpha/*metabolism ; Estrogen Receptor beta/*metabolism ; Estrogens/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Recurrence, Local/drug therapy/metabolism ; Signal Transduction ; Tamoxifen/*therapeutic use ; }, abstract = {Excessive exposure to estrogen has long been associated with an increased risk for developing breast cancer and anti-estrogen therapy is the gold standard of care in the treatment of estrogen receptor (ER) α-positive breast cancers. However, there are several mysteries concerning both anti-estrogen, tamoxifen, and estrogen. The most important of these are: (1) some ERα-positive breast cancers do not respond to tamoxifen; (2) some ERα-negative breast cancers do respond to tamoxifen; (3) initial or acquired resistance to tamoxifen occurs with recurrent tumors; (4) estrogen can cause marked tumor regression in long-term tamoxifen-resistant ERα-positive breast cancer. These mysteries indicate that we do not know enough about estrogen signaling to understand the effects of targeting these receptors in cancer. The discovery of ERβ, the second estrogen receptor, has added another level of complexity to estrogen signaling. This review summarizes recent publications and makes an updated portrait of ERα and ERβ in breast carcinogenesis and endocrine cancer therapy.}, } @article {pmid25432714, year = {2014}, author = {Hernández González, I and Navas Lobato, MÁ and Muncharaz, JF}, title = {Dislodgement and embolization of a left atrial appendage thrombus.}, journal = {Revista espanola de cardiologia (English ed.)}, volume = {67}, number = {12}, pages = {1054}, doi = {10.1016/j.rec.2014.02.018}, pmid = {25432714}, issn = {1885-5857}, mesh = {Aged, 80 and over ; Atrial Appendage/*diagnostic imaging ; Humans ; Male ; Thrombosis/*diagnostic imaging ; Ultrasonography ; }, } @article {pmid25430028, year = {2014}, author = {Yu, X and Liu, S and Chen, Z and Zhang, P and Zhang, J and Xu, L and Liu, Z and Ren, R}, title = {[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {36}, number = {8}, pages = {606-611}, pmid = {25430028}, issn = {0253-3766}, mesh = {Breast Neoplasms/*diagnosis ; Carcinoma, Ductal/*diagnosis ; *Diffusion Magnetic Resonance Imaging ; Humans ; Magnetic Resonance Imaging ; Retrospective Studies ; }, abstract = {OBJECTIVE: To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC).

METHODS: This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed.

RESULTS: The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001).

CONCLUSION: ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.}, } @article {pmid25429827, year = {2015}, author = {Zheng, Z and Shao, N and Weng, H and Li, W and Zhang, J and Zhang, L and Yang, L and Ye, S}, title = {Correlation between epidermal growth factor receptor and tumor stem cell markers CD44/CD24 and their relationship with prognosis in breast invasive ductal carcinoma.}, journal = {Medical oncology (Northwood, London, England)}, volume = {32}, number = {1}, pages = {275}, pmid = {25429827}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology ; CD24 Antigen/biosynthesis ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; ErbB Receptors/biosynthesis ; Female ; Humans ; Hyaluronan Receptors/biosynthesis ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplastic Stem Cells/*pathology ; Prognosis ; Retrospective Studies ; }, abstract = {We studied the correlation between epidermal growth factor receptor (EGFR) and the tumor stem cell markers CD44/CD24 in breast invasive ductal carcinoma (BIDC) and their relationship with prognosis. We analyzed the clinical data of 139 BIDC cases retrospectively, detecting EGFR, CD44, and CD24 expressions in tumor tissue using immunohistochemistry. The proportion of EGFR-, CD44-, and CD24-positive cases was 59.0, 62.3, and 30.9 %, respectively. The proportion of CD44-positive [76.9 % (p < 0.05)] and EGFR-positive [67.2 % (p = 0.108)] cases in the triple-negative breast cancer (TNBC) group was higher than that of the non-TNBC group. In the non-TNBC group, 36.5 % was CD24-positive, higher than that in the TNBC group but not statistically significant. The proportion of CD44-positive cases was significantly higher in the EGFR-positive group than in the EGFR-negative group (p = 0.017). EGFR-positive cases were significantly correlated with premenopausal status (p = 0.036), distant metastasis (p = 0.018), and estrogen receptor-negative status (p = 0.020). CD44-positive status was significantly correlated with human epidermal growth receptor 2 (HER2)-negative (p = 0.023), estrogen receptor-negative (p = 0.021), and progesterone receptor-negative status (p = 0.004). CD24-positive status was significantly correlated with HER2-positive status (p = 0.001). Kaplan-Meier survival analysis showed that TNBC patients had shorter survival. EGFR-positive and CD44-positive status were both correlated with shorter survival in the lymph node- and HR-negative groups, while CD24 positive was significantly correlated with poor survival in lymph node-negative and HR-positive patients. EGFR and CD44 expressions have a significantly positive correlation (p = 0.017) in BIDC. Patients both EGFR and CD44 positive had the worst outcome.}, } @article {pmid25429075, year = {2014}, author = {Keirsse, J and Laoui, D and Van Overmeire, E and Van Ginderachter, JA}, title = {Targeting cell-intrinsic and cell-extrinsic mechanisms of intravasation in invasive breast cancer.}, journal = {Science signaling}, volume = {7}, number = {353}, pages = {pe28}, doi = {10.1126/scisignal.aaa2104}, pmid = {25429075}, issn = {1937-9145}, mesh = {Animals ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Macrophages/*physiology ; Microfilament Proteins/*analysis ; Neoplasm Invasiveness/*physiopathology ; Neoplasm Proteins/*analysis ; Transendothelial and Transepithelial Migration/*physiology ; }, abstract = {The survival of breast cancer patients with metastatic disease has not markedly improved over recent decades, highlighting the need to better understand this process. In this issue of Science Signaling, Pignatelli et al. used freshly obtained invasive ductal carcinoma cells from patients to demonstrate the need for high abundance of the invasive isoform of the Mena protein (Mena(INV)) in cancer cells and colony-stimulating factor 1 (CSF-1)-mediated paracrine signaling in macrophages for efficient transendothelial migration and metastasis formation in all clinical breast cancer subtypes. Furthermore, the triple negative and HER2(+) subtypes, but not the ERPR(+)/HER2(-) subtype, had high CSF-1 receptor (CSF-1R) abundance and also partially used autocrine CSF-1/CSF-1R signaling for invasion. These data establish Mena(INV), CSF-1/CSF-1R, and macrophages as potential therapeutic targets for most human breast cancers.}, } @article {pmid25426255, year = {2014}, author = {Wolfson, B and Eades, G and Zhou, Q}, title = {Roles of microRNA-140 in stem cell-associated early stage breast cancer.}, journal = {World journal of stem cells}, volume = {6}, number = {5}, pages = {591-597}, pmid = {25426255}, issn = {1948-0210}, support = {F31 CA183522/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {An increasing body of evidence supports a stepwise model for progression of breast cancer from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Due to the high level of DCIS heterogeneity, we cannot currently predict which patients are at highest risk for disease recurrence or progression. The mechanisms of progression are still largely unknown, however cancer stem cell populations in DCIS lesions may serve as malignant precursor cells intimately involved in progression. While genetic and epigenetic alterations found in DCIS are often shared by IDC, mRNA and miRNA expression profiles are significantly altered. Therapeutic targeting of cancer stem cell pathways and differentially expressed miRNA could have significant clinical benefit. As tumor grade increases, miRNA-140 is progressively downregulated. miR-140 plays an important tumor suppressive role in the Wnt, SOX2 and SOX9 stem cell regulator pathways. Downregulation of miR-140 removes inhibition of these pathways, leading to higher cancer stem cell populations and breast cancer progression. miR-140 downregulation is mediated through both an estrogen response element in the miR-140 promoter region and differential methylation of CpG islands. These mechanisms are novel targets for epigenetic therapy to activate tumor suppressor signaling via miR-140. Additionally, we briefly explored the emerging role of exosomes in mediating intercellular miR-140 signaling. The purpose of this review is to examine the cancer stem cell signaling pathways involved in breast cancer progression, and the role of dysregulation of miR-140 in regulating DCIS to IDC transition.}, } @article {pmid25424886, year = {2015}, author = {Lacaze, I and Lalucque, H and Siegmund, U and Silar, P and Brun, S}, title = {Identification of NoxD/Pro41 as the homologue of the p22phox NADPH oxidase subunit in fungi.}, journal = {Molecular microbiology}, volume = {95}, number = {6}, pages = {1006-1024}, doi = {10.1111/mmi.12876}, pmid = {25424886}, issn = {1365-2958}, mesh = {Amino Acid Sequence ; Cytochrome b Group/metabolism ; Endoplasmic Reticulum/*enzymology ; Genome, Fungal ; Mutation ; Mycelium/ultrastructure ; NADPH Oxidases/chemistry/*genetics/*metabolism ; Phylogeny ; Podospora/*enzymology/genetics ; Sequence Analysis, DNA ; Superoxides/metabolism ; Vacuoles/*enzymology ; }, abstract = {NADPH oxidases (Nox) are membrane complexes that produce O2(-). Researches in mammals, plants and fungi highlight the involvement of Nox-generated ROS in cell proliferation, differentiation and defense. In mammals, the core enzyme gp91(phox)/Nox2 is associated with p22(phox) forming the flavocytochrome b558 ready for activation by a cytosolic complex. Intriguingly, no homologue of the p22(phox) gene has been found in fungal genomes, questioning how the flavoenzyme forms. Using whole genome sequencing combined with phylogenetic analysis and structural studies, we identify the fungal p22(phox) homologue as being mutated in the Podospora anserina mutant IDC(509). Functional studies show that the fungal p22(phox), PaNoxD, acts along PaNox1, but not PaNox2, a second fungal gp91(phox) homologue. Finally, cytological analysis of functional tagged versions of PaNox1, PaNoxD and PaNoxR shows clear co-localization of PaNoxD and PaNox1 and unravel a dynamic assembly of the complex in the endoplasmic reticulum and in the vacuolar system.}, } @article {pmid25421310, year = {2015}, author = {Buijs, JT and Matula, KM and Cheung, H and Kruithof-de Julio, M and van der Mark, MH and Snoeks, TJ and Cohen, R and Corver, WE and Mohammad, KS and Jonkers, J and Guise, TA and van der Pluijm, G}, title = {Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.}, journal = {The Journal of pathology}, volume = {235}, number = {5}, pages = {745-759}, pmid = {25421310}, issn = {1096-9896}, support = {U01 CA143057/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Bone Neoplasms/enzymology/genetics/*secondary ; Breast Neoplasms/chemically induced/enzymology/genetics/*pathology ; Carcinoma, Lobular/chemically induced/enzymology/genetics/*secondary ; Cdh1 Proteins/deficiency/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Mammary Neoplasms, Experimental/chemically induced/enzymology/genetics/*pathology ; Mice, Knockout ; Neoplasm Micrometastasis ; Protein Kinase Inhibitors/*toxicity ; Protein Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Pteridines/*toxicity ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta/*antagonists & inhibitors/metabolism ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Burden/drug effects ; Tumor Suppressor Protein p53/deficiency/genetics ; }, abstract = {Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most frequently occurring histological subtypes of breast cancer, accounting for 80-90% and 10-15% of the total cases, respectively. At the time of diagnosis and surgical resection of the primary tumour, most patients do not have clinical signs of metastases, but bone micrometastases may already be present. Our aim was to develop a novel preclinical ILC model of spontaneous bone micrometastasis. We used murine invasive lobular breast carcinoma cells (KEP) that were generated by targeted deletion of E-cadherin and p53 in a conditional K14cre;Cdh1((F/F));Trp53((F/F)) mouse model of de novo mammary tumour formation. After surgical resection of the growing orthotopically implanted KEP cells, distant metastases were formed. In contrast to other orthotopic breast cancer models, KEP cells readily formed skeletal metastases with minimal lung involvement. Continuous treatment with SD-208 (60 mg/kg per day), an orally available TGFβ receptor I kinase inhibitor, increased the tumour growth at the primary site and increased the number of distant metastases. Furthermore, when SD-208 treatment was started after surgical resection of the orthotopic tumour, increased bone colonisation was also observed (versus vehicle). Both our in vitro and in vivo data show that SD-208 treatment reduced TGFβ signalling, inhibited apoptosis, and increased proliferation. In conclusion, we have demonstrated that orthotopic implantation of murine ILC cells represent a new breast cancer model of minimal residual disease in vivo, which comprises key steps of the metastatic cascade. The cancer cells are sensitive to the anti-tumour effects of TGFβ. Our in vivo model is ideally suited for functional studies and evaluation of new pharmacological intervention strategies that may target one or more steps along the metastatic cascade of events.}, } @article {pmid25420392, year = {2014}, author = {Ŝoštarić Zadro, A and Fudurić, J and Frketić, I and Miletić, M and Zadro, Z and Martinac, M and Rasić, Z and Kordić, M and Rosić, D}, title = {Bilateral synchronous breast cancer.}, journal = {Collegium antropologicum}, volume = {38}, number = {3}, pages = {1043-1045}, pmid = {25420392}, issn = {0350-6134}, mesh = {Aged ; Breast Neoplasms/*pathology ; Female ; Humans ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {We report a rare case of synchronous bilateral breast cancer in 79-year-old female patient treated at our hospital. The tumors were discovered one year ago after a complete clinical and radiological (mammography, US) examination with cytopunction of tumor masses. Results came back and showed carcinomas of both breasts. Patient underwent surgical re moval of the both breasts with bilateral axillary lymphadenectomy. Later histological examination confirmed earlier diagnosis of invasive ductal carcinoma in both breasts in a G3 stage. After surgical removal of the tumors patient was also treated with radiotherapy. One year after bilateral mastectomy and axillary lymphadenectomy, clinical and radiological examination that included mammography and ultrasound of breast with tumor marker C15-3 which was 2.8, we did not found recurrence of the tumor.}, } @article {pmid25418428, year = {2015}, author = {Cavallo Marincola, B and Pediconi, F and Anzidei, M and Miglio, E and Di Mare, L and Telesca, M and Mancini, M and D'Amati, G and Monti, M and Catalano, C and Napoli, A}, title = {High-intensity focused ultrasound in breast pathology: non-invasive treatment of benign and malignant lesions.}, journal = {Expert review of medical devices}, volume = {12}, number = {2}, pages = {191-199}, doi = {10.1586/17434440.2015.986096}, pmid = {25418428}, issn = {1745-2422}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology/*therapy ; Female ; High-Intensity Focused Ultrasound Ablation/*methods ; Humans ; Magnetic Resonance Spectroscopy ; Treatment Outcome ; Ultrasonography ; }, abstract = {Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions.}, } @article {pmid25415921, year = {2014}, author = {Hamadeh, A and d'Allivy Kelly, O and Hahn, C and Meley, H and Bernard, R and Molpeceres, AH and Naletov, VV and Viret, M and Anane, A and Cros, V and Demokritov, SO and Prieto, JL and Muñoz, M and de Loubens, G and Klein, O}, title = {Full control of the spin-wave damping in a magnetic insulator using spin-orbit torque.}, journal = {Physical review letters}, volume = {113}, number = {19}, pages = {197203}, doi = {10.1103/PhysRevLett.113.197203}, pmid = {25415921}, issn = {1079-7114}, abstract = {It is demonstrated that the threshold current for damping compensation can be reached in a 5 μm diameter YIG(20 nm)|Pt(7 nm) disk. The demonstration rests upon the measurement of the ferromagnetic resonance linewidth as a function of I(dc) using a magnetic resonance force microscope (MRFM). It is shown that the magnetic losses of spin-wave modes existing in the magnetic insulator can be reduced or enhanced by at least a factor of 5 depending on the polarity and intensity of an in-plane dc current I(dc) flowing through the adjacent normal metal with strong spin-orbit interaction. Complete compensation of the damping of the fundamental mode by spin-orbit torque is reached for a current density of ∼3×10(11) A·m(-2), in agreement with theoretical predictions. At this critical threshold the MRFM detects a small change of static magnetization, a behavior consistent with the onset of an auto-oscillation regime.}, } @article {pmid25415740, year = {2014}, author = {Maglione, KD and Margolies, L and Jaffer, S and Szabo, J and Schmidt, H and Weltz, C and Sonnenblick, EB}, title = {Breast cancer in male-to-female transsexuals: use of breast imaging for detection.}, journal = {AJR. American journal of roentgenology}, volume = {203}, number = {6}, pages = {W735-40}, doi = {10.2214/AJR.14.12723}, pmid = {25415740}, issn = {1546-3141}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/*etiology ; Female ; Humans ; Male ; Mammography/*methods ; Middle Aged ; *Transgender Persons ; Transsexualism/*complications/*diagnostic imaging ; }, abstract = {OBJECTIVE: The purposes of this article are to describe two cases of breast cancer in male-to-female transsexuals and to review eight cases previously reported in the literature.

CONCLUSION: Breast cancer occurs in male-to-female transsexuals who receive high doses of exogenous estrogen and develop breast tissue histologically identical to that of a biologically female breast. This exposure to estrogen results in increased risk of breast cancer. The first patient described is a male-to-female transsexual with screening-detected ductal carcinoma in situ and a family history of breast cancer. The other patient is a male-to-female transsexual with invasive ductal carcinoma that was occult on diagnostic digital mammographic and ultrasound findings but visualized on digital breast tomosynthesis and breast MR images. The analysis of the eight previously reported cases showed that breast cancer in male-to-female transsexuals occurs at a younger age and is more frequently estrogen receptor negative than breast cancer in others born biologically male. Screening for breast cancer in male-to-female transsexuals should be undertaken for those with additional risk factors (e.g., family history, BRCA2 mutation, Klinefelter syndrome) and should be available to those who desire screening, preferably in a clinical trial.}, } @article {pmid25410489, year = {2015}, author = {Kim, HJ and Im, SA and Keam, B and Ham, HS and Lee, KH and Kim, TY and Kim, YJ and Oh, DY and Kim, JH and Han, W and Jang, IJ and Kim, TY and Park, IA and Noh, DY}, title = {ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy.}, journal = {Cancer science}, volume = {106}, number = {1}, pages = {86-93}, pmid = {25410489}, issn = {1349-7006}, mesh = {ATP Binding Cassette Transporter, Subfamily B/genetics ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/drug therapy/*genetics/mortality ; Carcinoma, Ductal, Breast/drug therapy/*genetics/mortality ; Chemotherapy, Adjuvant ; Cytochrome P-450 CYP3A/genetics ; Docetaxel ; Doxorubicin/administration & dosage ; Female ; Gene Frequency ; Genetic Association Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Polymorphism, Single Nucleotide ; Prognosis ; Proportional Hazards Models ; Taxoids/administration & dosage ; }, abstract = {Expression of the adenosine triphosphate-binding cassette B1 (ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. This study results provides valuable information on individualized therapy according to genotypes.}, } @article {pmid25404445, year = {2014}, author = {Iqbal, J and Shafi, AA and Alharthi, BN}, title = {Neoadjuvant chemotherapy in locally advanced breast cancer.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {24}, number = {11}, pages = {845-848}, pmid = {25404445}, issn = {1681-7168}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/mortality/pathology/*therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hormones/therapeutic use ; Humans ; *Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/epidemiology/therapy ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Saudi Arabia/epidemiology ; Severity of Illness Index ; Survival Analysis ; Survival Rate ; Treatment Outcome ; }, abstract = {OBJECTIVE: To assess the response to Neoadjuvant Chemotherapy (NAC) in Locally Advanced Breast Cancer (LABC) in terms of pathological response, overall survival and feasibility of breast conservation surgery.

STUDY DESIGN: Case series.

PLACE AND DURATION OF STUDY: King Fahad Medical City (KFMC), Riyadh, from January 2009 to July 2012.

METHODOLOGY: All patients of LABC who received NAC and underwent surgery were included. All these patients received the GORG001 regimen (FEC+Docetaxal+Cisplatin+/-Herceptin). After chemotherapy patients were offered surgery either Modified Radical Mastectomy (MRM) or Breast Conservation Surgery (BCS) +Radiotherapy. Patients were then followed to exclude local or distant metastasis. RESULTS were described in percentage.

RESULTS: The median age at the time of diagnosis was 46.8 years. While complete response was achieved in 24 (44.4%) patients, 14 (25.9%) of the patients had partial response and 16 (29.6%) progressed clinically. Surgery was performed in these patients after NAC. Forty (74%) patients had MRM, 14 (25.9%) had BCS; all had axillary lymph node dissection. Invasive ductal carcinoma accounted for 92% of cases. Vascular invasion was present in 12 (22%) of the patients. Estrogen / progesterone receptor positivity was 61%. Thirty nine percent of the patients were Her2 positive. On an average, follow-up of 4 - 51 months in the MRM group, one patient had resection margin (deep) positive and was treated with adjuvant therapy. While in the BCS group after 3 - 26 months of follow-up, one patient had resection margin positive (medial margin) and underwent MRM, while no patient had local or distant metastasis in both the groups.

CONCLUSION: NAC caused down staging of disease in LABC making more conservative surgery feasible. BCC should be considered as an option for treatment of LABC, however, longer follow-up is recommended.}, } @article {pmid25400793, year = {2014}, author = {Liu, W and Zhu, H and Zhou, X}, title = {Synchronous bilateral non-Hodgkin's diffuse large B-cell lymphoma of the breast and left breast invasive ductal carcinoma: a case report and review of literature.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {10}, pages = {7042-7048}, pmid = {25400793}, issn = {1936-2625}, mesh = {Biomarkers, Tumor/analysis ; Bone Marrow Transplantation ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Chemotherapy, Adjuvant ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Immunohistochemistry ; Lymphoma, Large B-Cell, Diffuse/chemistry/*pathology/surgery ; Mastectomy, Radical ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasms, Multiple Primary ; Predictive Value of Tests ; Ultrasonography, Mammary ; }, abstract = {Lymphoma of the breast is unusual, and synchronous bilateral lymphoma and carcinoma of the breast is extremely rare. We present the case of a 51-year-old woman who found a mass in her left breast. Ultrasound scan findings revealed nodules at the 2 o'clock position in her left breast and focal dilation of the duct at the 8-9 o'clock and 10 o'clock position in her right and left breasts, respectively. A left breast ultrasound-guided core needle biopsy and right breast segmental excisional biopsy were performed. Pathological and immunohistochemical examination revealed left breast invasive ductal carcinoma and right breast diffuse large B-cell lymphoma of the non-germinal center type. Pathological examination of the left breast modified radical mastectomy specimen revealed synchronous invasive ductal carcinoma (grade III) and diffuse large B-cell lymphoma. The patient received chemotherapy and bone marrow transplantation in another hospital. Based on a review of the relevant literature, we discuss the diagnosis, clinical features, treatment, and prognosis of synchronous breast lymphoma and invasive ductal carcinoma.}, } @article {pmid25400790, year = {2014}, author = {Matsuda, I and Watanabe, T and Enomoto, Y and Takatsuka, Y and Miyoshi, Y and Hirota, S}, title = {Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {10}, pages = {7020-7027}, pmid = {25400790}, issn = {1936-2625}, mesh = {Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell, Marginal Zone/chemistry/*pathology ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasm Regression, Spontaneous ; Neoplasms, Multiple Primary ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.}, } @article {pmid25400746, year = {2014}, author = {Lv, ZD and Kong, B and Liu, XP and Dong, Q and Niu, HT and Wang, YH and Li, FN and Wang, HB}, title = {CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {10}, pages = {6671-6678}, pmid = {25400746}, issn = {1936-2625}, mesh = {Animals ; Breast Neoplasms/genetics/immunology/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/immunology/*metabolism/mortality/secondary ; *Cell Proliferation ; Chemokine CXCL12/genetics/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; MCF-7 Cells ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Signal Transduction ; Time Factors ; Transfection ; Tumor Burden ; }, abstract = {Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.}, } @article {pmid25400696, year = {2014}, author = {Lau, AC and Nabeshima, K and Csankovszki, G}, title = {The C. elegans dosage compensation complex mediates interphase X chromosome compaction.}, journal = {Epigenetics & chromatin}, volume = {7}, number = {1}, pages = {31}, pmid = {25400696}, issn = {1756-8935}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. The DCC contains a subcomplex (condensin I(DC)) similar to the evolutionarily conserved condensin complexes which play fundamental roles in chromosome dynamics during mitosis and meiosis. Therefore, mechanisms related to mitotic chromosome condensation have been long hypothesized to mediate dosage compensation. However experimental evidence was lacking.

RESULTS: Using 3D FISH microscopy to measure the volumes of X and chromosome I territories and to measure distances between individual loci, we show that hermaphrodite worms deficient in DCC proteins have enlarged interphase X chromosomes when compared to wild type. By contrast, chromosome I is unaffected. Interestingly, hermaphrodite worms depleted of condensin I or II show no phenotype. Therefore X chromosome compaction is specific to condensin I(DC). In addition, we show that SET-1, SET-4, and SIR-2.1, histone modifiers whose activity is regulated by the DCC, need to be present for the compaction of the X chromosome territory.

CONCLUSION: These results support the idea that condensin I(DC), and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction. Our results link condensin-mediated chromosome compaction, an activity connected to mitotic chromosome condensation, to chromosome-wide repression of gene expression in interphase.}, } @article {pmid25397622, year = {2014}, author = {Kong, EJ and Chun, KA and Bom, HS and Lee, J and Lee, SJ and Cho, IH}, title = {Initial experience of integrated PET/MR mammography in patients with invasive ductal carcinoma.}, journal = {Hellenic journal of nuclear medicine}, volume = {17}, number = {3}, pages = {171-176}, doi = {10.1967/s002449910142}, pmid = {25397622}, issn = {1790-5427}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Multimodal Imaging/*methods ; Neoplasm Invasiveness ; Pilot Projects ; Positron-Emission Tomography/*methods ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; Systems Integration ; Whole Body Imaging/methods ; }, abstract = {The purpose of this study was to evaluate the feasibility of integrated fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance ((18)F-FDG PET/MR) mammography in invasive ductal carcinoma (IDC) patients. From August 2012 to March 2013, we enrolled 42 consecutive breast cancer patients who received whole- body PET/MR and subsequent PET/MR mammography by an integrated PET/MR scanner and were scheduled for surgery within 2 weeks after the of scan. On the whole body PET/MR, 2-point Dixon VIBE, coronal T1w image, axial T2w image, and post-contrast T1 sequences were acquired with simultaneous PET acquisition. For PET/MR mammography, T1w, T2w, and dynamic contrast-enhancement (DCE) sequences were acquired using a breast coil during simultaneous PET acquisition. We compared the detectability of the lesions between whole-body PET/MR and PET/MR mammography. Forty-eight IDC (1.89±1.19cm of width) were diagnosed in 42 women. Lesion conspicuity in (18)F-FDG PET was equivalent between whole-body PET/MR and PET/MR mammography; both PET/MR images showed 38 hypermetabolic masses. In the analysis of 10 IDC with <1.0cm wide lesions, only 1 IDC showed (18)F-FDG uptake, and 4 IDC were noted on whole-body PET/MR; however, all 10 IDC showed a depictable mass on PET/MR mammography. In the analysis of 38 IDC >1.0cm wide, 37 IDC showed (18)F-FDG uptake, and 38 IDC were detected on both whole-body PET/MR and PET/MR mammography. The overall sensitivity was 79.2% (38/48) on PET, 87.5% (42/48) on whole-body PET/MR, and 100% on PET/MR mammography. The SUV between whole-body PET/MR and PET/MR mammography showed strong and highly significant correlation (r=0.987, P<0.001). In conclusion, our results, although in a limited number of cases show that integrated PET/MR mammography is feasible and has the advantage of combining high-resolution breast images with metabolic images. Furthermore, PET/MR mammography could provide an accurate diagnosis in case of IDC that are less than 1cm in size.}, } @article {pmid25395490, year = {2015}, author = {Ginter, PS and Petrova, K and Hoda, SA}, title = {The grossly "rusty" tumor of breast: invasive ductal carcinoma with osteoclast-like giant cells.}, journal = {International journal of surgical pathology}, volume = {23}, number = {1}, pages = {32-33}, doi = {10.1177/1066896914558266}, pmid = {25395490}, issn = {1940-2465}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Giant Cells/*pathology ; Humans ; Middle Aged ; Osteoclasts/*pathology ; }, } @article {pmid25394563, year = {2015}, author = {Liu, Y and Liu, T and Sun, Q and Niu, M and Jiang, Y and Pang, D}, title = {Downregulation of Ras GTPase‑activating protein 1 is associated with poor survival of breast invasive ductal carcinoma patients.}, journal = {Oncology reports}, volume = {33}, number = {1}, pages = {119-124}, doi = {10.3892/or.2014.3604}, pmid = {25394563}, issn = {1791-2431}, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*metabolism/mortality ; Carcinoma, Ductal, Breast/*metabolism/mortality ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Expression ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; p120 GTPase Activating Protein/genetics/*metabolism ; }, abstract = {Ras GTPase‑activating protein 1 (RASA1) functions to inactivate Ras‑GTPase and inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during human cancer development and progression. This study investigated RASA1 expression in normal and breast cancer tissue specimens to determine the association with prognosis of breast cancer patients. Two sets of patient samples (45 fresh tissues and 373 paraffin‑embedded tissues) were analyzed for RASA1 expression using RT‑qPCR and immunohisto-chemistry. The results showed that the expression of RASA1 mRNA was lower in breast cancer tissues than in the corresponding normal tissues (P<0.001). Additionally, RASA1 expression was reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression was significantly associated with tumor lymph node metastasis (P=0.002), advanced TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki‑67 (P=0.009), higher histological grade (P<0.001), and triple‑negative breast cancer (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter disease‑free survival (P=0.036) and overall survival (P<0.001) of breast cancer patients. RASA1 expression, together with tumor lymph‑node metastasis, TNM stage, Her‑2 expression, and triple‑negative breast cancer were independent factors in predicting survival of breast cancer patients. In conclusion, RASA1 expression is frequently reduced in breast cancer tissues, and the reduced RASA1 expression is associated with breast cancer progression and poor survival and disease‑free survival of patients.}, } @article {pmid25391703, year = {2014}, author = {Yanagihara, K and Takei, H and Iida, S and Yamashita, K and Kurita, T and Iwamoto, M and Saegusa, H and Uchida, E}, title = {Grade 4 epistaxis in a woman with metastatic breast cancer treated with bevacizumab: a case report.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {81}, number = {5}, pages = {333-336}, doi = {10.1272/jnms.81.333}, pmid = {25391703}, issn = {1347-3409}, mesh = {Adult ; Angiogenesis Inhibitors/*adverse effects ; Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*secondary ; Epistaxis/*chemically induced ; Female ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Paclitaxel/administration & dosage ; Severity of Illness Index ; }, abstract = {We describe a 39-year-old woman with metastatic breast cancer who had grade 4 epistaxis induced by bevacizumab. The patient visited our outpatient clinic with complaints of a lump in her right breast, fatigue, dyspnea, abdominal distention, appetite loss, and weight loss of 10 kg over 1 year. Liver dysfunction was detected, with elevated levels of aspartate aminotransferase (271 IU/L), alanine aminotransferase (100 IU/L), alkaline phosphatase (4,205 IU/L), total bilirubin (2.7 mg/dL), and direct bilirubin (2.1 mg/dL). A secondary liver tumor that occupied most of the liver volume was found, and bone metastasis, ascites, and pleural effusion were also discovered. The Eastern Cooperative Oncology Group performance status was 2. A core needle biopsy of the right breast tumor revealed invasive ductal carcinoma of the breast (nuclear grade 1) that was positive for estrogen receptor and progesterone receptor and negative for human epidermal growth factor receptor 2 overexpression and had a high Ki-67 score. We chose combination chemotherapy with paclitaxel (80 mg/m(2) on days 1, 8, and 15) and bevacizumab (10 mg/kg on days 1 and 15) for 28 days (1 cycle). After completion of the first cycle of chemotherapy, the ascites and pleural effusion decreased, and the metastatic liver tumor shrank. The performance status improved from 2 to 1. On day 3 of the third cycle of chemotherapy, however, she began having persistent epistaxis. On day 6, she lost consciousness and was transported to the emergency room of our hospital. The hemoglobin level was 5.6 g/dL. Blood transfusion and endoscopic hemostasis were immediately started. Bevacizumab was discontinued, and paclitaxel alone was continued; after this change, epistaxis did not recur.}, } @article {pmid25385074, year = {2014}, author = {Wong, H and Lau, S and Cheung, P and Wong, TT and Parker, A and Yau, T and Epstein, RJ}, title = {Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {826}, pmid = {25385074}, issn = {1471-2407}, mesh = {Adult ; Australia ; Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*secondary ; Carcinoma, Lobular/*chemistry/*secondary ; Cell Proliferation ; Chemotherapy, Adjuvant ; Female ; Hong Kong ; Humans ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Tumor Burden ; }, abstract = {BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity.

METHODS: The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed.

RESULTS: Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC tumors failed to demonstrate any such inverse relationship (p >0.6).

CONCLUSION: These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.}, } @article {pmid25382741, year = {2014}, author = {Wu, YT and Chen, ST and Chen, CJ and Kuo, YL and Tseng, LM and Chen, DR and Kuo, SJ and Lai, HW}, title = {Breast cancer arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment policy.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {335}, pmid = {25382741}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*pathology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Combined Modality Therapy ; Female ; Fibroadenoma/*pathology/therapy ; Follow-Up Studies ; *Health Policy ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Review Literature as Topic ; }, abstract = {BACKGROUND: Breast cancer arising within a fibroadenoma (BcaFad) is rare; the rate varies from 0.002% to 0.125% in fibroadenoma specimens. Owing to its rarity, the clinicopathologic feature and treatment principle of BcaFad is still not clear. Therefore, the aim of this study was to perform a collective analysis of case reports in the literature to identify the characteristics and optimal treatment for BcaFad.

METHODS: We analyzed an aggregated sample of 30 patients with BcaFad from case reports in the literature (n=24 cases) and our present study (n=6 cases). We collected and analyzed the clinicopathologic features and prognoses of patients with BcaFad, as well as treatments they received.

RESULTS: The patients' mean age at diagnosis was 46.9 years. Twenty BcaFad patients (66.7%) received breast-conserving surgery (BCS), and nine other patients (30.0%) were treated with mastectomy. The rate of lymph node metastasis in BcaFad patients was 23.8%. The breakdown of the histological types of BcaFad was invasive ductal carcinoma (53.3%), followed by ductal carcinoma in situ (23.3%), lobular carcinoma in situ (16.7%) and invasive lobular carcinoma (13.3%). More than half of patients with positive hormone receptor status received hormone therapy. Most BcaFad patients with lymph node metastases received chemotherapy, and 20.0% of BcaFad patients treated with BCS received further radiotherapy. Only one patient had recurrence after surgery, and another had lung metastasis when diagnosed with BcaFad.

CONCLUSIONS: Most BcaFad patients could be managed by BCS. Adjuvant radiotherapy could be performed, but was not mandatory. Chemotherapy should be considered as a treatment option in the presence of lymph node metastasis.}, } @article {pmid25381287, year = {2014}, author = {Pliskin, R and Bar-Tal, D and Sheppes, G and Halperin, E}, title = {Are leftists more emotion-driven than rightists? The interactive influence of ideology and emotions on support for policies.}, journal = {Personality & social psychology bulletin}, volume = {40}, number = {12}, pages = {1681-1697}, doi = {10.1177/0146167214554589}, pmid = {25381287}, issn = {1552-7433}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Conflict, Psychological ; *Culture ; *Emotions ; Female ; Group Processes ; Humans ; Israel ; Jews ; Male ; Middle Aged ; *Politics ; Young Adult ; }, abstract = {Although emotions and ideology are important factors guiding policy support in conflict, their interactive influence remains unclear. Based on prior findings that ideological leftists' beliefs are more susceptible to change than rightists' beliefs, we tested a somewhat counterintuitive extension that leftists would be more susceptible to influence by their emotional reactions than rightists. In three laboratory studies, inducing positive and negative emotions affected Jewish-Israeli leftists', but not rightists', support for conciliatory policies toward an adversarial (Studies 1 and 3) and a non-adversarial (Study 2) outgroup. Three additional field studies showed that positive and negative emotions were related to leftists', but not rightists', policy support in positive as well as highly negative conflict-related contexts, among both Jewish (Studies 4 and 5) and Palestinian (Study 6) citizens of Israel. Across different conflicts, emotions, conflict-related contexts, and even populations, leftists' policy support changed in accordance with emotional reactions more than rightists' policy support.}, } @article {pmid25379017, year = {2014}, author = {Scheiber, MN and Watson, PM and Rumboldt, T and Stanley, C and Wilson, RC and Findlay, VJ and Anderson, PE and Watson, DK}, title = {FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.}, journal = {Neoplasia (New York, N.Y.)}, volume = {16}, number = {10}, pages = {801-813}, pmid = {25379017}, issn = {1476-5586}, support = {P01 CA078582/CA/NCI NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; P01CA78582/CA/NCI NIH HHS/United States ; P30 CA 138313/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/genetics/pathology ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Protein c-fli-1/*genetics/metabolism ; Proto-Oncogene Proteins c-ets/genetics ; }, abstract = {ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.}, } @article {pmid25373614, year = {2014}, author = {Rai, R and Zhu, L and Chen, H and Gupta, AP and Sze, SK and Zheng, J and Ruedl, C and Bozdech, Z and Featherstone, M}, title = {Genome-wide analysis in Plasmodium falciparum reveals early and late phases of RNA polymerase II occupancy during the infectious cycle.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {959}, pmid = {25373614}, issn = {1471-2164}, mesh = {Antibodies, Monoclonal/pharmacology ; Binding Sites/genetics ; Chromatin Immunoprecipitation ; Cluster Analysis ; Computational Biology ; Erythrocytes/parasitology ; Gene Dosage ; *Genome, Protozoan ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Malaria, Falciparum/*parasitology ; Molecular Sequence Annotation ; Phosphorylation ; Plasmodium falciparum/*genetics/*metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Subunits/antagonists & inhibitors ; RNA Polymerase II/antagonists & inhibitors/chemistry/*metabolism ; RNA, Messenger/genetics ; Transcription, Genetic ; Transcriptional Activation ; }, abstract = {BACKGROUND: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts.

RESULTS: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC.

CONCLUSIONS: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite.}, } @article {pmid25372365, year = {2014}, author = {Aggarwal, A and Liu, ML and Krasnow, SH}, title = {Breast cancer in male veteran population: an analysis from VA cancer registry.}, journal = {The Journal of community and supportive oncology}, volume = {12}, number = {8}, pages = {293-297}, doi = {10.12788/jcso.0066}, pmid = {25372365}, issn = {2330-7749}, abstract = {BACKGROUND: Male breast cancer is rare and makes up < 1% of all cases of breast cancers. Treatment and survival stage per stage is mainly based on what is known from female breast cancer.

OBJECTIVES: We determined the pathological features, stage, treatment of breast cancer in male veterans and their survival outcome.

METHODS: Medical records of male patients diagnosed with breast cancer at the Veterans Affairs Medical Centers of Washington DC, Baltimore, Maryland, and Martinsburg, West Virginia, from 1992-2012 were reviewed after iInstitutional review board approval.

RESULTS: From 1995-2012, 51 male patients with breast cancer were identifed from cancer registry. Of those, 57% were African American, 41% white, and 2% other race. Median age was 68 years (range, 44-86 years). Palpable mass was presenting symptoms in 80%, and gynecomastia or bloody nipple discharge in 16%. Family history of breast cancer in immediate family was positive in 11 patients without mention of BRCA genes except in one who was BRCA2-positve. ER/PR (estrogen-/progesterone-receptor) was positive in 71%, ER-positive/PR-negative in 2%, ER-positive/PR-positive /HER2-positive in 4%, ER-negative/PR-negative /HER2-triple negative in 4%. In all, 41% and 57% had right and left breast cancer, respectively; 80% had mastectomy, 36% had lymph node involvement (1-13 LN), 90% had invasive ductal carcinoma, 8% DCIS, and 2% sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV. Twenty four percent of the patients had combination chemotherapy, and 66% were given tamoxifen. Eight percent had relapsed or recurrent disease within 1-5 years of their diagnosis and died within 2-12 years after the relapse. At median follow-up of 174 months (range, 4 months-19 years), 56% had died, 42% were alive, and 6% had been lost to follow-up.

LIMITATIONS: This is a very small retrospective chart review. Further large prospective studies are desired.

CONCLUSIONS: Median age at diagnosis of breast cancer seems to be higher in men (70 years) than it is in women (60 years). Invasive ductal carcinoma is the main pathology, and 73% of the tumors were ER-positive. The survival rate at more than 10 years of follow-up was about 40%. Stage versus survival revealed no difference in mortality.}, } @article {pmid25368291, year = {2014}, author = {Klopfer, K and Delahunt, B and Adamson, M and Samaratunga, H}, title = {Value of uroplakin III in distinguishing variants of primary bladder urothelial carcinoma from malignancy metastatic to the urinary bladder.}, journal = {Anticancer research}, volume = {34}, number = {11}, pages = {6779-6784}, pmid = {25368291}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Giant Cell/metabolism/*secondary ; Carcinoma, Large Cell/metabolism/*secondary ; Carcinoma, Papillary/metabolism/*secondary ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Urinary Bladder Neoplasms/metabolism/*pathology ; Uroplakin III/*metabolism ; }, abstract = {BACKGROUND: Urothelial carcinoma (UC) variants can be difficult to differentiate from carcinoma metastatic to the bladder.

MATERIALS AND METHODS: We examined immunostaining for uroplakin III in 43 cases of primary bladder UC variants including micropapillary UC (n=19), nested variant of UC (n=2), pleomorphic giant-cell carcinoma (n=8), plasmacytoid UC (n=4), lymphoepithelioma-like carcinoma (n=2), large cell undifferentiated carcinoma (n=2), UC with abundant myxoid stroma (n=3) and lipid cell variant (n=3) and in 11 tumors from other organs metastatic to the bladder. These tumors included invasive ductal carcinoma of the breast (n=2), colorectal adenocarcinoma (n=4), endometrioid adenocarcinoma (n=1) and serous papillary carcinoma of the uterus (n=1) melanoma (n=1), embryonal carcinoma of the testis (n=1), and renal clear cell carcinoma (n=1).

RESULTS: Out of the 43 UC variants, 35 (81%) were positive for uroplakin III, including micropapillary, lipid cell variant and UC with abundant myxoid stroma. Pleomorphic giant cell carcinoma, plasmacytoid UC and nested variant of UC were less commonly positive. Of the 11 metastatic tumors, six were found to be positive for uropIakin III: metastatic colorectal adenocarcinoma, clear cell carcinoma of the kidney and embryonal carcinoma of testis.

CONCLUSION: UP III Positivity for uroplakin III is not found only in primary bladder UC variants, but in some tumors that have metastatized to the bladder. Staining for uroplakin III alone should not be taken as evidence of UC.}, } @article {pmid25365176, year = {2014}, author = {Ruibal, Á and Aguiar, P and Del Río, MC and Padín-Iruegas, ME and Arias, JI and Herranz, M}, title = {CA15.3 serum concentrations in older women with infiltrating ductal carcinomas of the breast.}, journal = {International journal of molecular sciences}, volume = {15}, number = {11}, pages = {19870-19876}, pmid = {25365176}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*diagnosis/pathology ; Carcinoembryonic Antigen/*blood ; Carcinoma, Ductal/*diagnosis/pathology ; Female ; Humans ; *Luminescent Measurements ; Lymphatic Metastasis ; Mucin-1/*blood ; Neoplasm Grading ; }, abstract = {Breast cancer is currently becoming a disease of the elderly. We have studied the relation between CA 15.3 serum concentrations and clinical-pathological parameters in 69 women with IDC aged over 70 years (76.3±4.2; range: 71-88; median 76). A group of 205 women with the same tumor but aged <70 years (62.8±4.0; range: 55-70; median 63) was also considered for comparison. Tumor size, axillary lymph node involvement, distant metastasis and histological grade were taken account. Serum CA 15.3 was determined by luminescence assay. CA 15.3 serum concentrations ranged between 6 and 85 U/mL (median 22.9 U/mL), and were higher only in patients with greater (qualitative and quantitative; p: 0.041) tumor size. Our results show that in women with IDCs, and aged over 70 years, serum CA 15.3 serum concentrations are associated exclusively with a greater tumor size, being these findings different to those described in women with the same subtype of tumor considered as a whole or with lower age.}, } @article {pmid25364993, year = {2014}, author = {Otto, MW and Hearon, BA and McHugh, RK and Calkins, AW and Pratt, E and Murray, HW and Safren, SA and Pollack, MH}, title = {A randomized, controlled trial of the efficacy of an interoceptive exposure-based CBT for treatment-refractory outpatients with opioid dependence.}, journal = {Journal of psychoactive drugs}, volume = {46}, number = {5}, pages = {402-411}, pmid = {25364993}, issn = {0279-1072}, support = {R01 DA017904/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Anxiety/therapy ; *Cognitive Behavioral Therapy ; Female ; Humans ; Male ; Middle Aged ; Opioid-Related Disorders/*therapy ; Outpatients ; Treatment Outcome ; }, abstract = {Many patients diagnosed with opioid dependence do not adequately respond to pharmacologic, psychosocial, or combination treatment, highlighting the importance of novel treatment strategies for this population. The current study examined the efficacy of a novel behavioral treatment focusing on internal cues for drug use (Cognitive Behavioral Therapy for Interoceptive Cues; CBT-IC) relative to an active comparison condition, Individual Drug Counseling (IDC), when added to methadone maintenance treatment (MMT) among those who had not responded to MMT. Participants (N=78) were randomly assigned to receive 15 sessions of CBT-IC or IDC as an adjunct to ongoing MMT and counseling. Oral toxicology screens were the primary outcome. Results indicated no treatment differences between CBT-IC and IDC and a small, significant reduction of self-reported drug use, but no change on toxicology screens. Tests of potential moderators, including sex, anxiety sensitivity, and coping motives for drug use, did not yield significant interactions. Among opioid-dependent outpatients who have not responded to MMT and counseling, the addition of IDC or CBT-IC did not result in additive outcome benefits. These results highlight the need for more potent treatment strategies for opioid dependence, particularly among those who do not fully respond to frontline treatment.}, } @article {pmid25364575, year = {2014}, author = {Zhang, L and Comertpay, S and Shimizu, D and DeMay, RM and Carbone, M and Honda, SA and Eaves, JM}, title = {Axillary metaplastic breast carcinoma with ipsilateral pectoral invasive ductal carcinoma: an unusual presentation.}, journal = {Case reports in oncological medicine}, volume = {2014}, number = {}, pages = {938509}, pmid = {25364575}, issn = {2090-6706}, abstract = {We report a case of axillary metaplastic breast carcinoma (MBC) with triple negative (ER-/PR-/Her2-) phenotype, concurrent with multifocal invasive ductal carcinoma (IDC) of ipsilateral pectoral breast (ER+/PR+/Her2-) in a 60-year-old woman. The two tumors demonstrate different morphology, immunophenotype, and opposite response to neoadjuvant chemotherapy of paclitaxol, adriamycin, and cyclophosphamide. Methylation analysis of human androgen receptor (HUMARA) on X-chromosome identified monoclonal pattern of X-chromosome inactivation in MBC and mosaic pattern in the IDC. Stem cell origin of MBC is suggested in this case. Clinicopathological features, imaging findings, biological markers, chemoradiation management, and prognosis of MBC are reviewed in comparison to invasive ductal carcinoma. Our case and literature review suggest that traditional chemotherapy applicable to IDC is less effective towards MBC. However, new chemotherapy protocols targeting stem cell and multimodality management of MBC are promising. Recognition of unusual presentation of MBC will help tailor therapy towards tumor with worse prognosis.}, } @article {pmid25360699, year = {2014}, author = {Ma, FJ and Liu, ZB and Hu, X and Ling, H and Li, S and Wu, J and Shao, ZM}, title = {Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {10}, pages = {e111639}, pmid = {25360699}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Myeloid Differentiation Factor 88/*metabolism ; Prognosis ; Toll-Like Receptor 4/*metabolism ; }, abstract = {PURPOSE: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).

METHODS: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.

RESULTS: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006).

CONCLUSIONS: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.}, } @article {pmid25357113, year = {2014}, author = {Jorns, JM and Thomas, DG and Healy, PN and Daignault, S and Vickery, TL and Snider, JE and Mardis, ER and Davies, SR and Ellis, MJ and Visscher, DW}, title = {Estrogen receptor expression is high but is of lower intensity in tubular carcinoma than in well-differentiated invasive ductal carcinoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {138}, number = {11}, pages = {1507-1513}, pmid = {25357113}, issn = {1543-2165}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; T32 CA083654/CA/NCI NIH HHS/United States ; P30 CA91842/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/*metabolism/*pathology ; Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Differentiation ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Middle Aged ; Molecular Typing ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {CONTEXT: Tubular carcinoma (TC) is a rare, luminal A subtype of breast carcinoma with excellent prognosis, for which adjuvant chemotherapy is usually contraindicated.

OBJECTIVE: To examine the levels of estrogen receptor (ER) and progesterone receptor expression in cases of TC and well-differentiated invasive ductal carcinoma as compared to normal breast glands and to determine if any significant differences could be detected via molecular testing.

DESIGN: We examined ER and progesterone receptor via immunohistochemistry in tubular (N = 27), mixed ductal/tubular (N = 16), and well-differentiated ductal (N = 27) carcinomas with comparison to surrounding normal breast tissue. We additionally performed molecular subtyping of 10 TCs and 10 ductal carcinomas via the PAM50 assay.

RESULTS: Although ER expression was high for all groups, TC had statistically significantly lower ER staining percentage (ER%) (P = .003) and difference in ER expression between tumor and accompanying normal tissue (P = .02) than well-differentiated ductal carcinomas, with mixed ductal/tubular carcinomas falling between these 2 groups. Mean ER% was 79%, 87%, and 94%, and mean tumor-normal ER% differences were 13.6%, 25.9%, and 32.6% in tubular, mixed, and ductal carcinomas, respectively. Most tumors that had molecular subtyping were luminal A (9 of 10 tubular and 8 of 10 ductal), and no significant differences in specific gene expression between the 2 groups were identified.

CONCLUSIONS: Tubular carcinoma exhibited decreased intensity in ER expression, closer to that of normal breast parenchyma, likely as a consequence of a high degree of differentiation. Lower ER% expression by TC may represent a potential pitfall when performing commercially available breast carcinoma prognostic assays that rely heavily on ER-related gene expression.}, } @article {pmid25355267, year = {2014}, author = {Qing, Z and Zou, W and Luo, J and Wen, Q and Fan, S}, title = {[p53 protein expression in HER2-negative breast invasive ductal carcinoma].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {39}, number = {10}, pages = {1016-1022}, doi = {10.11817/j.issn.1672-7347.2014.10.005}, pmid = {25355267}, issn = {1672-7347}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Prognosis ; Receptor, ErbB-2 ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {OBJECTIVE: To determine the expression of p53 and its clinical significance in HER2-negative breast invasive ductal carcinoma (BIDC).

METHODS: The expression of p53, ER and PR in the HER2-negative BIDC was detected by immunohistochemistry and the results were analyzed by SPSS10.0 software packet, chi-square test, spearman's correlation analysis, Kaplan-Meier survival curves and Cox regression analysis.

RESULTS: The positive expression of p53 protein in BIDC with pathological grade III was significantly higher than that with grade I (P<0.05), but there was no significant correlation between the expression of p53 and age, clinical stage, or lymph node metastasis status in the BIDC. The positive expression of p53 protein in BIDC with ER-positive was significantly lower than that with ER-negative (P<0.01). The positive expression of p53 protein was significantly lower in BIDC with common expression of ER and PR than that with negative expression of ER or PR (P<0.05). The HER2-negative BIDC patients with p53-positive expression had a lower 5 year survival than those with p53-negative expression.

CONCLUSION: The positive expression of p53 protein might have significant prognostic value and is an independent prognostic marker in HER2 -negative BIDC.}, } @article {pmid25349738, year = {2014}, author = {Zaidi, M and Khan, S and Farooqi, NB and Abbas, K and Idrees, R}, title = {Effect of formalin fixation on surgical margins in breast cancer surgical specimen.}, journal = {International journal of breast cancer}, volume = {2014}, number = {}, pages = {121838}, pmid = {25349738}, issn = {2090-3170}, abstract = {Margin analysis in breast surgery is an important predictor of local recurrence and can have vital impact on the postoperative treatment planning. Objective. The aim was to assess the mean reduction in the closest tumor-free surgical margin in millimeters of breast cancer specimens following formalin fixation. Materials and Methods. We conducted a cross-sectional study at the Aga Khan University Hospital from March 30, 2010 to January 20, 2011. One hundred consecutive breast tumour surgical specimens which had macroscopically visible tumour were included. The cancer type included both in situ and invasive cancers. Excluded were the patients who had previous surgery or systemic/radiation therapy. The closest tumor-free margin was recorded and compared with the margin after formalin fixation. P value of <0.05 was considered significant. Results. The mean age of our 100 patients was 53 years with the majority of the patients having undergone mastectomy for predominantly invasive ductal carcinoma. Following formalin fixation, the mean reduction of the closest tumor-free margin was noted as 2.14 mm which was found statistically significant. Conclusion. Considerable shrinkage of tumor-free surgical margins of breast cancer specimen was noted after formalin fixation. This inference can have implications on the postoperative management plan.}, } @article {pmid25346122, year = {2014}, author = {Zhang, Z and Bu, H and Huang, H and Zhang, J and Lang, Z and Zhao, T and Wang, J and Liao, D and Wei, B}, title = {[Matrix-producing metaplastic carcinoma: a clinicopathologic and prognostic analysis of 16 cases with review of literature].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {8}, pages = {528-532}, pmid = {25346122}, issn = {0529-5807}, mesh = {Adult ; Aged ; Cadherins/metabolism ; Carcinoma/*metabolism/*pathology ; China ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/*metabolism ; Neoplasm Recurrence, Local ; Prognosis ; S100 Proteins/metabolism ; Triple Negative Breast Neoplasms/*metabolism/*pathology ; }, abstract = {OBJECTIVE: To study the clinicopathologic features, immunophenotype and prognosis of matrix-producing metaplastic carcinoma (MPC).

METHODS: Sixteen cases of MPC diagnosed between 2002 and 2012 in West China Hospital were identified. The clinicopathologic features were analyzed. Immunohistochemistry for E-cadherin, S-100 protein, CK5/6, HCK, PCK, CK7, CK8, p63, SMA, EMA, CD99, MSA, CK14, EGFR, ER, PR, HER2 and Ki-67 was performed with EnVision method. The clinical outcome was evaluated and compared to matched controls of invasive ductal carcinoma.

RESULTS: All patients were women and ranged in age from 29 to 69 years (median age 48 years). The median size of primary tumor was 4 cm. Most of the tumors were well-circumscribed with expansile and multinodular appearance. Histology showed invasive carcinoma with a direct transition from carcinoma to cartilaginous/chondromyxoid matrix without an intervening spindle cell component. Tumor distribution was either nodular or diffuse. The matrix component accounted for 10%-80% of the tumor volume. All the tumors were strongly positive for S-100 protein and basal-like cytokeratin with triple negative phenotype (ER, PR and HER2 negative). Alcian blue stain was positive for the cartilaginous/chondromyxoid matrix. Compared with invasive ductal carcinoma, patients with MPC had increased locoregional recurrence (P = 0.010), increased distant recurrence (P = 0.011) and shorter disease-free survival (P = 0.017).

CONCLUSIONS: MPC is a rare variant of mammary metaplastic carcinoma with unique characteristics of morphology and immunohistochemical staining pattern. This subtype seems to have aggressive biologic behavior.}, } @article {pmid25344624, year = {2014}, author = {Riobó Serván, P and Sierra Poyatos, R and Soldo Rodríguez, J}, title = {Low and no calorie sweeteners (LNCS); myths and realities.}, journal = {Nutricion hospitalaria}, volume = {30 Suppl 2e}, number = {}, pages = {49-55}, doi = {10.3305/nh.2014.30.sup2e.8288}, pmid = {25344624}, issn = {1699-5198}, mesh = {Diabetes Mellitus/prevention & control ; *Energy Intake ; Humans ; Neoplasms/chemically induced ; Obesity/prevention & control ; *Sweetening Agents/adverse effects ; }, abstract = {Since their introduction in the market, there has been much debate regarding the health effects of low and no calorie sweetners (LNCS). Therefore, through this review, we aim to establish scientific information about the most commonly used LNCS by the food industry. Key questions about uses, safety, and weight control are reviewed. Scientific evidence revised concludes that LNCS available on the market are safe and no epidemiological relationship has been established with the development of non-communicable diseases, including different kind of cancer in humans. Also, LCNS combined with physical activity and a healthy lifestyle can play a significant role in weight loss and the maintenance of a healthy weight. But non nutritive sweeteners will be helpful only as long as people don't eat additional calories later as compensation. Even more, LNCS represent an additional instrument in the dietary treatment of people with diabetes for metabolic control, without avoiding sweet taste.}, } @article {pmid25343577, year = {2014}, author = {Hasler, BS and Hirschberger, G and Shani-Sherman, T and Friedman, DA}, title = {Virtual peacemakers: mimicry increases empathy in simulated contact with virtual outgroup members.}, journal = {Cyberpsychology, behavior and social networking}, volume = {17}, number = {12}, pages = {766-771}, pmid = {25343577}, issn = {2152-2723}, mesh = {Adult ; Arabs/*psychology ; *Computer Simulation ; *Empathy ; Female ; Humans ; *Imitative Behavior ; Jews/*psychology ; Male ; Negotiating/*psychology ; Nonverbal Communication ; *Psychological Distance ; Racism/psychology ; *Social Identification ; Students/psychology ; *User-Computer Interface ; Young Adult ; }, abstract = {This research examined virtual-human interactions as a new form of simulated contact between members of groups in conflict. A virtual human representing an outgroup member (a Palestinian) interacted with 60 Jewish Israeli participants in an experimental study. We manipulated postural mimicry by the virtual interaction partner during a conversation about a sensitive conflict issue. Mimicry increased empathy toward the Palestinians, irrespective of participants' feelings toward the Palestinians prior to the experiment. Further, mimicked participants who reported a priori negative feelings toward Palestinians expressed more sympathy toward their Palestinian virtual interaction partner, rated themselves as closer to him, and perceived the interaction as more harmonious compared to participants in a counter-mimicry condition. The results underscore the impact of mimicry on intergroup interactions, especially on individuals who harbor negative feelings toward the outgroup. The use of virtual-human interactions in obtaining this effect reveals the still widely unexplored potential of technology-enhanced conflict resolution.}, } @article {pmid25343550, year = {2014}, author = {Hu, A and Sun, M and Yan, D and Chen, K}, title = {Clinical significance of mTOR and eIF4E expression in invasive ductal carcinoma.}, journal = {Tumori}, volume = {100}, number = {5}, pages = {541-546}, doi = {10.1700/1660.18176}, pmid = {25343550}, issn = {2038-2529}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Adult ; Aged ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carrier Proteins/metabolism ; Cell Cycle Proteins ; Eukaryotic Initiation Factor-4E/*metabolism ; Eukaryotic Initiation Factors/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Molecular Targeted Therapy ; Phosphoproteins/metabolism ; Prognosis ; Protein Transport ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {AIMS AND BACKGROUND: Mammalian target of rapamycin (mTOR) is one of the serine-threonine protein kinases and plays an important regulatory role in cell growth. Eukaryotic translation initiation factor 4E (eIF4E) and 4E binding protein (4EBP) are the downstream proteins of mTOR signaling pathway and are the most efficient speed regulator of eukaryotic mRNA translation. The aim of the study was to investigate the clinical significance of mTOR, eIF4E and 4EBPs expression in invasive ductal carcinoma.

METHODS: Fresh biopsy specimens of invasive ductal carcinoma tissues and normal breast tissues were collected from 45 patients with breast cancer. The expressions of mTOR, eIF4E and 4EBPs in specimens were detected by an immunohistochemical SP method, and the relationship of mTOR, eIF4E and 4EBPS expressions and of their expressions with tumor metastasis were analyzed.

RESULTS: Expressions of mTOR, eIF4E and 4EBPs in invasive ductal carcinoma were significantly higher than in normal breast tissue (P <0.05). mTOR expression was positively correlated with eIF4E and 4EBP expression in invasive ductal carcinoma (P <0.05). The positive rates of mTOR, eIF4E and 4EBPs in patients with lymph node metastasis were significantly higher than in patients without lymph node metastasis (P <0.05).

CONCLUSIONS: Increased expressions of mTOR and eIF4E in invasive ductal carcinoma may be correlated with the occurrence and metastasis of breast cancer.}, } @article {pmid25340906, year = {2014}, author = {Liu, Z and Yu, D and Luo, W and Yang, J and Lu, J and Gao, S and Li, W and Zhao, W}, title = {Impact of oral health behaviors on dental caries in children with intellectual disabilities in Guangzhou, China.}, journal = {International journal of environmental research and public health}, volume = {11}, number = {10}, pages = {11015-11027}, pmid = {25340906}, issn = {1660-4601}, mesh = {Adolescent ; Cerebral Palsy/epidemiology ; Child ; China/epidemiology ; Cross-Sectional Studies ; Dental Care/*statistics & numerical data ; Dental Caries/*epidemiology ; Disabled Children/*statistics & numerical data ; Female ; Humans ; Intellectual Disability/*epidemiology ; Male ; Sex Factors ; Surveys and Questionnaires ; Toothbrushing/*statistics & numerical data ; }, abstract = {Dental care is consistently reported as one of the primary medical needs of children with disabilities (IDC). The aim of the present study was to explore the influence of oral health behaviors on the caries experience in children with intellectual disabilities in Guangzhou, China. A cross-sectional study was carried out in 477 intellectually disabled children, 12 to 17 years old, who were randomly selected from special educational schools in Guangzhou. A self-administered parental questionnaire was used to collect data on socio-demographic characteristics and oral health behavior variables, and 450 valid questionnaires were returned. Multiple regression analysis was used to examine the factors associated with dental caries. The average age of those in the sample was 14.6 years (SD = 1.3), 68.4% of whom were male, and the caries prevalence rate was 53.5% (DMFT = 1.5 ± 2.0). The factors significantly affecting the development of dental caries in IDC included gender, the presence or absence of cerebral palsy, and the frequency of dental visits and toothbrushing. In conclusion, the presence of cerebral palsy contributed to an increase risk of caries experience in intellectually disabled children, while toothbrushing more than twice a day and routine dental visits were caries-protective factors. Oral health promotion action may lead to a reduction in dental caries levels in IDC.}, } @article {pmid25339043, year = {2014}, author = {Wan Abdul Rahman, WF and Fauzi, MH and Jaafar, H}, title = {Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {19}, pages = {8441-8445}, doi = {10.7314/apjcp.2014.15.19.8441}, pmid = {25339043}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Cross-Sectional Studies ; *DNA Methylation ; Female ; Follow-Up Studies ; Homeodomain Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.}, } @article {pmid25338984, year = {2014}, author = {Zhang, L and Liu, YJ and Jiang, SQ and Cui, H and Li, ZY and Tian, JW}, title = {Ultrasound utility for predicting biological behavior of invasive ductal breast cancers.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {19}, pages = {8057-8062}, doi = {10.7314/apjcp.2014.15.19.8057}, pmid = {25338984}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Ultrasonography, Mammary/*statistics & numerical data ; Young Adult ; }, abstract = {PURPOSE: The aim of the study was to evaluate the correlation of ultrasound features with breast cancer molecular status.

MATERIALS AND METHODS: A retrospective review was performed of ultrasound findings in 263 patients diagnosed with breast invasive ductal carcinoma for comparison with immunohistochemistric results were obtained from each lesion. Relationships between ultrasound findings and molecular status were investigated by using multiple regression analysis by means of stepwise logistic regression. Differences in ultrasound criteria were assessed among women with different molecular status.

RESULTS: ER positivity was associated with small size, lobulate, angular or spiculated margin contours, absence of calcification, posterior tumor shadowing and low elasticity score; PR positivity was associated with small size, lobulate or angular or spiculated margin contours and absence of calcification; HER2 positivity was associated with presence of calcification and absence of any echogenic halo. The calculated models of predicted molecular status were accurate and discriminating with AUCs of 0.78, 0.74, and 0.74, respectively.

CONCLUSIONS: Breast cnacer ultrasound features show some correlation with the molecular status. These models may help to expand the scope of ultrasound in predicting tumor biology.}, } @article {pmid25337201, year = {2014}, author = {Ren, J and Chen, QC and Jin, F and Wu, HZ and He, M and Zhao, L and Yu, ZJ and Yao, WF and Mi, XY and Wang, EH and Wei, MJ}, title = {Overexpression of Rsf-1 correlates with pathological type, p53 status and survival in primary breast cancer.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {9}, pages = {5595-5608}, pmid = {25337201}, issn = {1936-2625}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/surgery ; Carcinoma/*chemistry/mortality/pathology/surgery ; Chi-Square Distribution ; Chromatin Assembly and Disassembly ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Nuclear Proteins/*analysis ; Predictive Value of Tests ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Time Factors ; Trans-Activators/*analysis ; Treatment Outcome ; Tumor Burden ; Tumor Suppressor Protein p53/*analysis ; Up-Regulation ; Young Adult ; }, abstract = {AIM: The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma.

METHODS: A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated.

RESULTS: Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent × intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer.

CONCLUSIONS: High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.}, } @article {pmid25336664, year = {2015}, author = {Benezet-Mazuecos, J and Rubio, JM and Cortés, M and Iglesias, JA and Calle, S and de la Vieja, JJ and Quiñones, MA and Sanchez-Borque, P and de la Cruz, E and Espejo, A and Farré, J}, title = {Silent ischaemic brain lesions related to atrial high rate episodes in patients with cardiac implantable electronic devices.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {17}, number = {3}, pages = {364-369}, doi = {10.1093/europace/euu267}, pmid = {25336664}, issn = {1532-2092}, mesh = {Aged ; Aged, 80 and over ; *Asymptomatic Diseases ; Atrial Fibrillation/diagnosis/*epidemiology ; Brain Ischemia/diagnostic imaging/*epidemiology ; *Cardiac Resynchronization Therapy Devices ; *Defibrillators, Implantable ; Electrocardiography, Ambulatory ; Female ; Humans ; Incidence ; Ischemic Attack, Transient/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Pacemaker, Artificial ; Proportional Hazards Models ; Prospective Studies ; Stroke/diagnostic imaging/*epidemiology ; Tomography, X-Ray Computed ; }, abstract = {AIMS: Monitoring capabilities of cardiac implantable electronic devices have revealed that a large proportion of patients present silent atrial fibrillation (AF) detected as atrial high rate episodes (AHREs). Atrial high rate episodes >5 min have been linked to increased risk of clinical stroke, but a high proportion of ischaemic brain lesions (IBLs) could be subclinical.

METHODS AND RESULTS: We prospectively analysed the incidence of AHRE > 5 min in 109 patients (56% men, aged 74 ± 9 years) and the presence of silent IBL on computed tomography (CT) scan. Mean CHADS2 and CHA2DS2VASc scores were 2.3 ± 1.3 and 3.9 ± 1.6, respectively. Seventy-five patients (69%) had no history of AF or stroke/transient ischaemic attack (TIA). After 12 months, 28 patients (25.7%) showed at least one AHRE. Patients with AHREs were more likely to have history of AF. Computed tomography scan showed silent IBL in 28 (25.7%). The presence of IBL was significantly related to older patients, prior history of AF or stroke/TIA, higher CHADS2 or CHA2DS2VASc scores, and the presence of AHRE. Multivariable analysis demonstrated that AHRE was an independent predictor for silent IBL in overall population [hazard ratio (HR) 3.05 (1.06-8.81; P < 0.05)] but also in patients without prior history of AF or stroke/TIA [HR 9.76 (1.76-54.07; P < 0.05)].

CONCLUSION: Cardiac implantable electronic devices can accurately detect AF as AHRE. Atrial high rate episodes were associated to a higher incidence of silent IBL on CT scan. Atrial high rate episodes represent a kind of silent AF where management recommendations are lacking despite the fact that a higher embolic risk is present.}, } @article {pmid25335542, year = {2014}, author = {Azim, HA and Malek, RA and Azim, HA}, title = {Pathological features and prognosis of lobular carcinoma in Egyptian breast cancer patients.}, journal = {Women's health (London, England)}, volume = {10}, number = {5}, pages = {511-518}, doi = {10.2217/whe.14.48}, pmid = {25335542}, issn = {1745-5065}, mesh = {Adult ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Disease-Free Survival ; Egypt/epidemiology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {AIM: To illustrate the differences between invasive lobular and ductal carcinomas (ILCs and IDCs) in terms of baseline demographics, pathologic features and recurrence in Egyptian breast cancer patients.

PATIENTS & METHODS: Retrospective analysis of breast cancer patients diagnosed and treated between 2000 and 2008 was performed.

RESULTS: 176 (8.5%) and 1758 (85%) cases were diagnosed with ILC and IDC, respectively. Compared with IDC, ILC was less observed in patients under 35 years of age (3.4 vs 9.3%; p = 0.009), and was associated with more bilaterality (p = 0.001), advanced tumor stage (p = 0.027) and nodal involvement (p = 0.004). On the other hand, IDC was significantly associated with more luminal B-like phenotype (16.9 vs 8.1%; p < 0.001) and more HER2-enriched disease (11.5 vs 2.7%; p < 0.001). At a median follow-up time of 64 months, ILC histology was independently associated with better disease-free survival (hazard ratio: 0.58; 95% CI: 0.36-0.93; p = 0.023). Bone and peritoneal relapses were more common in ILC, while lung relapses were more common in IDC.

CONCLUSION: ILC has distinct biologic and prognostic features that may warrant different therapeutic approaches.}, } @article {pmid25327792, year = {2014}, author = {Wang, X and Zheng, X and Lin, X and Shi, Y and He, Y and Chen, G}, title = {[Methylation of Runx3 promoter in different breast lesions].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {7}, pages = {447-450}, pmid = {25327792}, issn = {0529-5807}, mesh = {Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; *DNA Methylation ; Female ; Fibroadenoma/*metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Promoter Regions, Genetic ; }, abstract = {OBJECTIVE: To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues.

METHODS: One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis.

RESULTS: Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively.

CONCLUSIONS: Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.}, } @article {pmid25327790, year = {2014}, author = {Yang, G and Guo, L and Jin, H and Li, J and Ding, H}, title = {[Clinicopathologic observation of carcinomas arising in fibroepithelial neoplasms of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {7}, pages = {437-441}, pmid = {25327790}, issn = {0529-5807}, mesh = {Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Fibroepithelial/*pathology ; Phyllodes Tumor/*pathology ; Rare Diseases/pathology ; }, abstract = {OBJECTIVE: To investigate the pathology, diagnosis and differential diagnosis of carcinomas arising in fibroepithelial neoplasms of the breast.

METHODS: Morphological observation and immunohistochemistry using MaxVision method were performed in fifty-four cases of carcinoma arising from fibroepithelial neoplasms of the breast from January 2003 to February 2014.

RESULTS: Thirty-eight cases of carcinoma arose from fibroadenomas. Twelve cases were classical lobular carcinoma in situ (LCIS). Twenty-one cases were ductal carcinoma in situ (DCIS), including four cases of low-grade, ten cases of intermediate-grade, six cases of high-grade and one case of apocrine. One case was mixed DCIS and LCIS. Three cases were infiltrating ductal carcinoma (IDC) accompanied with DCIS. One case was spindle cell metaplastic carcinoma. Sixteen cases arose from phyllodes tumours. Six cases arose from benign phyllodes tumours, including four cases of low-grade DCIS, one case of high-grade DCIS, and one case of classical LCIS with micro-invasion (diameter 0.9 mm). Three cases arose from borderline phyllodes tumours, including one case of classical LCIS, one case of intermediate-grade DCIS, and one case of invasive lobular carcinoma (ILC) with LCIS. Seven cases arose from malignant phyllodes tumours, including two cases each of low-grade DCIS and intermediate-grade DCIS, one case of high-grade DCIS, one case of apocrine DCIS, and one case of mixed IDC with DCIS. By immunohistochemistry, LCIS and ILC were diffusely positive for ER and PR. Low-grade DCIS was diffusely positive for ER and PR (> 90%), intermediate-grade DCIS was 70%-90% positive, high-grade DCIS was negative for ER and 20%-30% positive for PR, apocrine DCIS was both negative, and IDC was 40%-90% positive. The spindle cell metaplastic carcinoma was negative for ER and PR, but showed diffuse or scattered positivity for CK5/6 and p63.

CONCLUSIONS: Carcinomas arising from fibroepithelial neoplasms of the breast are rare, showing unusual clinical presentation, and are characterized by in situ or invasive carcinomas in a background of fibroepithelial neoplasms. The accurate diagnosis depends on the recognition of the background fibroepithelial neoplasms and assessment of the nature of the epithelial proliferation, supplemented by immunohistochemistry when necessary.}, } @article {pmid25323837, year = {2015}, author = {Atasoy, MM and Tasali, N and Çubuk, R and Narin, B and Deveci, U and Yener, N and Çelik, L}, title = {Vacuum-assisted stereotactic biopsy for isolated BI-RADS 4 microcalcifications: evaluation with histopathology and midterm follow-up results.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {21}, number = {1}, pages = {22-27}, pmid = {25323837}, issn = {1305-3612}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Calcinosis/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Female ; Humans ; Image-Guided Biopsy/*methods ; Middle Aged ; Retrospective Studies ; Stereotaxic Techniques ; Vacuum ; }, abstract = {PURPOSE: The aim of this study was to evaluate the 10-gauge vacuum-assisted stereotactic biopsy (VASB) of isolated Breast Imaging Reporting and Data System (BI-RADS) 4 microcalcifications, using histology and follow-up results.

METHODS: From January 2011 to June 2013, VASB was performed on 132 lesions, and 66 microcalcification-only lesions of BI-RADS 4 were included into our study. VASB was performed using lateral decubitis stereotaxy for all patients. Pathologic results of VASB and further surgical biopsies were reviewed retrospectively. Patients who were diagnosed to have benign lesions by VASB were referred for follow-up. VASB and surgical histopathology results were compared to determine the underestimation ratios.

RESULTS: Fifteen out of 66 lesions from 63 patients (median age, 47 years; range, 34-88 years) were identified as malignant by VASB. Pathological results after surgery revealed three cases of invasive ductal carcinoma among the 12 VASB-diagnosed ductal carcinoma in situ (DCIS) lesions, for a DCIS underestimation rate of 25%. The atypical ductal hyperplasia underestimation rate was 0% for the three lesions. The follow-up period was at least 10 months, with an average of 22.7 months for all patients and 21.2 months for patients with VASB-diagnosed benign lesions. None of the patients had malignancy during the follow-ups. The false-negative rate was 0% in the follow-up of 48 patients.

CONCLUSION: VASB should be the standard method of choice for BI-RADS 4 microcalcifications. This method obviates the need for a surgical procedure in 73% of BI-RADS 4 microcalcification-only patients.}, } @article {pmid25323475, year = {2015}, author = {Truin, W and Roumen, RM and Siesling, S and van der Heiden-van der Loo, M and Duijm, LE and Tjan-Heijnen, VC and Voogd, AC}, title = {Patients with invasive lobular breast cancer are less likely to undergo breast-conserving surgery: a population based study in the Netherlands.}, journal = {Annals of surgical oncology}, volume = {22}, number = {5}, pages = {1471-1478}, doi = {10.1245/s10434-014-4175-7}, pmid = {25323475}, issn = {1534-4681}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/pathology/*surgery ; Carcinoma, Ductal, Breast/epidemiology/pathology/*surgery ; Carcinoma, Lobular/epidemiology/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Netherlands/epidemiology ; Prognosis ; }, abstract = {PURPOSE: The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC).

METHODS: Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS.

RESULTS: A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71).

CONCLUSION: The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.}, } @article {pmid25320626, year = {2014}, author = {Jung, HN and Han, BK and Ko, EY and Shin, JH}, title = {Initial experience with magnetic resonance-guided vacuum-assisted biopsy in korean women with breast cancer.}, journal = {Journal of breast cancer}, volume = {17}, number = {3}, pages = {270-278}, pmid = {25320626}, issn = {1738-6756}, abstract = {PURPOSE: The aim of this study is to describe our initial experience with magnetic resonance (MR)-guided biopsy and to determine the malignancy rate of additional lesions identified by MR only in Korean women with breast cancer.

METHODS: A retrospective review identified 22 consecutive patients with breast cancer who had undergone MR-guided vacuum-assisted biopsies (VAB) of MR-only identified lesions from May 2009 to October 2011.We evaluated the rate of compliance, the technical success for MR-guided VAB and the MR imaging findings of the target lesions. VAB histology was compared with surgical histology and follow-up imaging findings.

RESULTS: The biopsy recommendations for MR-only identified lesions were accepted in 46.8% (22/47) of patients. One of 22 procedures failed due to the target's posterior location. Among 21 MR-guided VAB procedures, the target lesions were considered as a mass in 12 cases and a nonmass enhancement in nine cases. VAB histology revealed malignancies in 14% (3/21) of cases, high-risk lesions in 24% (5/21) and benign lesions in 62% (13/21). Eleven cases (52%, 11/21) had a positive surgical correlation, and one of them was upgraded from atypical ductal hyperplasia to invasive ductal carcinoma. In the remaining 10 lesions, follow-up breast ultrasound and mammography were available (range, 15-44 months; mean, 32.1 months) and did not show suspicious lesions. The final malignancy rate was 19% (4/21).

CONCLUSION: MR-guided VAB for MR-only identified lesions yielded a 19% malignancy rate in Korean women with breast cancer. MR-guided VAB helps surgeons avoid an unnecessary wide excision or additional excisional biopsy.}, } @article {pmid25309649, year = {2014}, author = {Galukande, M and Wabinga, H and Mirembe, F and Karamagi, C and Asea, A}, title = {Molecular breast cancer subtypes prevalence in an indigenous Sub Saharan African population.}, journal = {The Pan African medical journal}, volume = {17}, number = {}, pages = {249}, pmid = {25309649}, issn = {1937-8688}, support = {087540//Wellcome Trust/United Kingdom ; 100891//Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Adult ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prevalence ; Triple Negative Breast Neoplasms/*epidemiology/pathology ; Uganda/epidemiology ; }, abstract = {INTRODUCTION: Sub-Saharan Africa is predicted to face an unprecedented growth of cancers including breast cancer. There are indications of a significant burden of aggressive and late stage breast disease among premenopausal women in sub-Saharan Africa; because hormonal status tests are not routinely done, many women are given anti-hormonal therapy empirically. There is paucity of data on breast cancer molecular subtypes and their characteristics among women in sub Saharan Africa. The objective is to determine the prevalence of breast cancer molecular phenotypes among Ugandan women.

METHODS: This was a cross sectional descriptive study, conducted at a tertiary hospital in Africa. Eligible participants' formalin fixed and paraffin embedded sections were evaluated. H & E stains and Immunochemistry (Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal growth factor Receptor (HER2)) were performed. Ethical approval was obtained.

RESULTS: A total of 226 patient samples were evaluated. The mean age was 45 years (SD 14);the prevalence of Triple Negative Breast Cancer (TNBC) was 34% (77/226), Luminal A 38% (83/226), HER2 positive was 22% (49/226), and Luminal B was 5% (13/226). High-grade (III) tumors were 68%, stage III and IV constituted 75% of presentations. Histological type was mostly invasive ductal carcinoma. Most patients (55%) were from rural areas.

CONCLUSION: Ugandan women had an over representation of TNBC and high-grade breast tumors. Underlying reasons ought to be investigated. The empirical use of tamoxifen (anti-hormonal therapy) should be reexamined.}, } @article {pmid25307858, year = {2015}, author = {Zhao, T and Liao, B and Yao, J and Liu, J and Huang, R and Shen, P and Peng, Z and Gui, H and Chen, X and Zhang, P and Zhu, Y and Li, X and Wei, Q and Zhou, Q and Zeng, H and Chen, N}, title = {Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?.}, journal = {The Prostate}, volume = {75}, number = {3}, pages = {225-232}, doi = {10.1002/pros.22906}, pmid = {25307858}, issn = {1097-0045}, mesh = {Adenocarcinoma/*secondary ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Multiple Primary/*pathology ; Prognosis ; Prostatic Neoplasms/*pathology ; }, abstract = {BACKGROUND: Intraductal carcinoma of prostate (IDC-P) was usually found to be co-exist with conventional aggressive prostate adenocarcinoma. The presence of IDC-P was considered as an adverse pathological factor, which was associated with high Gleason score, large prostate volume and accelerated disease progression. However, no any information is available on the presence of IDC-P diagnosed by needle biopsy in patients with metastatic prostate cancer. We investigated the incidence and prognostic value of intraductal carcinoma of prostate (IDC-P) in initial diagnosed metastatic prostate cancer.

METHODS: We included 278 patients with initial diagnosed metastatic prostate cancer treated between 2008 and 2011, all the pathological diagnosis were from ultrasonic-guided transperineal needle biopsy. IDC-P was strictly defined according to Epstein's criteria. Analyzed factors included age, Eastern Cooperative Oncology Group (ECOG) score, clinical T staging, Gleason scores, baseline prostate specific antigen (PSA), alkaline phosphatase (ALP), hemoglobin (HGB), PSA normalization, and the presence of IDC-P.

RESULTS: Totally, IDC-P was found in 57/278 (20.5%) cases. Univariate analysis showed that, compared with cases without IDC-P, cases with IDC-P was definitely associated with much shorter CRPC-free survival (CFS) time (46.05 ± 1.39 vs. 22.98 ± 1.80 months, P = 0.000) and OS time (50.38 ± 1.18 vs. 36.43 ± 2.10 months, P = 0.000). Multivariate analysis showed that the presence of IDC-P was the only independent prognostic factor associated with poor CFS (HR = 4.886, P = 0.011) and OS (HR = 1.945, P = 0.020). Further sub-analysis showed, even among patients with higher Gleason score (≥8) (n = 158), IDC-P was still significantly and inversely associated with CFS and OS (the median CFS time: 40 versus 22 months; P = 0.000; the median OS time: 54 vs. 36 months, P = 0.000). Again, Cox's regression model confirmed that only the presence of IDC-P was still not only an independent prognostic factor predicting shorter time of CRPC (HR = 4.031, P = 0.035), but also for poorer OS (HR = 2.499, P = 0.006).

CONCLUSIONS: The presence of IDC-P in initial diagnosed metastatic prostate cancer, even among patients with more aggressive pattern, was firstly found to be significantly and independently associated with earlier occurrence of CRPC and poorer OS. We recommended the presence of IDC-P should be a routine record in pathological report of clinical diagnosis and other potential therapeutic regimen might be added to intervene in the integrated therapy as early as possible. Prostate 75:225-232, 2015. © 2014 Wiley Periodicals, Inc.}, } @article {pmid25306264, year = {2014}, author = {Sun, Y and Liang, F and Cao, W and Wang, K and He, J and Wang, H and Wang, Y}, title = {Prognostic value of poorly differentiated clusters in invasive breast cancer.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {310}, pmid = {25306264}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Observer Variation ; Prognosis ; Reproducibility of Results ; Survival Analysis ; }, abstract = {BACKGROUND: Our study aimed to assess the prognostic value of poorly differentiated clusters (PDCs) in invasive breast cancer.

METHODS: A total of 146 cases of operable invasive ductal carcinoma that was not otherwise specified (IDC-NOS), from 2002 to 2009, were pathologically reviewed. Cancer clusters with five or more cancer cells and lacking gland-like structures were counted from a field containing maximum clusters in H & E slides under a×20 objective lens (0.950 mm2 field of vision).

RESULTS: Tumors with <5, 5 to 9, and ≥10 clusters were graded as G1, G2, and G3, respectively (n=41, 60, and 45 tumors, respectively). An interobserver test showed good reproducibility, with a Cohen's kappa coefficient of 0.739. The PDC grade was significantly associated with N stage (P<0.001), lymphovascular invasion (P=0.007), tumor budding grade (P<0.001), relapse rate (P<0.001), and death rate (P<0.001). Survival analyses revealed that the PDC grade was a significant prognostic factor for disease-free survival (hazard ratio 3.811; P<0.001) and overall survival (hazard ratio 3.730; P=0.001), independent of T stage, N stage, or tumor budding grade.

CONCLUSIONS: The PDC grade is an independent prognostic factor of IDC-NOS. Considering the simplicity and availability of this method relative to conventional clinical pathology, PDCs may serve as a novel prognostic histological characteristic in IDC-NOS.}, } @article {pmid25306216, year = {2014}, author = {Volinia, S and Nuovo, G and Drusco, A and Costinean, S and Abujarour, R and Desponts, C and Garofalo, M and Baffa, R and Aeqilan, R and Maharry, K and Sana, ME and Di Leva, G and Gasparini, P and Dama, P and Marchesini, J and Galasso, M and Manfrini, M and Zerbinati, C and Corrà, F and Wise, T and Wojcik, SE and Previati, M and Pichiorri, F and Zanesi, N and Alder, H and Palatini, J and Huebner, KF and Shapiro, CL and Negrini, M and Vecchione, A and Rosenberg, AL and Croce, CM and Garzon, R}, title = {Pluripotent stem cell miRNAs and metastasis in invasive breast cancer.}, journal = {Journal of the National Cancer Institute}, volume = {106}, number = {12}, pages = {}, pmid = {25306216}, issn = {1460-2105}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; U01 CA154200/CA/NCI NIH HHS/United States ; U01 CA166905/CA/NCI NIH HHS/United States ; U01 CA152758/CA/NCI NIH HHS/United States ; }, mesh = {Breast/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*secondary ; Female ; Humans ; Lymphatic Metastasis ; MicroRNAs/*analysis ; *Neoplastic Stem Cells ; *Pluripotent Stem Cells ; }, abstract = {BACKGROUND: The purpose of this study is to determine whether microRNA for pluripotent stem cells are also expressed in breast cancer and are associated with metastasis and outcome.

METHODS: We studied global microRNA profiles during differentiation of human embryonic stem cells (n =26) and in breast cancer patients (n = 33) and human cell lines (n = 35). Using in situ hybridization, we then investigated MIR302 expression in 318 untreated breast cancer patients (test cohort, n = 22 and validation cohort, n = 296). In parallel, using next-generation sequencing data from breast cancer patients (n = 684), we assessed microRNA association with stem cell markers. All statistical tests were two-sided.

RESULTS: In healthy tissues, the MIR302 (high)/MIR203 (low) asymmetry was exclusive for pluripotent stem cells. MIR302 was expressed in a small population of cancer cells within invasive ductal carcinoma, but not in normal breast (P < .001). Furthermore, MIR302 was expressed in the tumor cells together with stem cell markers, such as CD44 and BMI1. Conversely, MIR203 expression in 684 breast tumors negatively correlated with CD44 (Spearman correlation, Rho = -0.08, P = .04) and BMI1 (Rho = -0.11, P = .004), but positively correlated with differentiation marker CD24 (Rho = 0.15, P < .001). Primary tumors with lymph node metastasis had cancer cells showing scattered expression of MIR302 and widespread repression of MIR203. Finally, overall survival was statistically significantly shorter in patients with MIR302-positive cancer cells (P = .03).

CONCLUSIONS: In healthy tissues the MIR302(high)/MIR203(low) asymmetry was characteristic of embryonic and induced pluripotency. In invasive ductal carcinoma, the MIR302/MIR203 asymmetry was associated with stem cell markers, metastasis, and shorter survival.}, } @article {pmid25299798, year = {2015}, author = {Matsubayashi, RN and Imanishi, M and Nakagawa, S and Takahashi, R and Akashi, M and Momosaki, S and Muranaka, T}, title = {Breast ultrasound elastography and magnetic resonance imaging of fibrotic changes of breast disease: correlations between elastography findings and pathologic and short Tau inversion recovery imaging results, including the enhancement ratio and apparent diffusion coefficient.}, journal = {Journal of computer assisted tomography}, volume = {39}, number = {1}, pages = {94-101}, doi = {10.1097/RCT.0000000000000155}, pmid = {25299798}, issn = {1532-3145}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis ; Elasticity Imaging Techniques/*methods ; Female ; Fibrosis/pathology ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: Ultrasound (US) elastography provides information regarding tissue hardness and is expected to become a novel diagnostic tool for breast disease. In contrast, magnetic resonance (MR) images reflect the tissue characteristics. Fibrosis of the stroma of breast diseases may affect their hardness. We investigated the correlation among elasticity score (ES) and signal intensity of short Tau inversion recovery MR images, enhancement ratio, apparent diffusion coefficient (ADC), and the fibrosis in the breast lesions.

MATERIALS AND METHODS: We reviewed the findings of US elastography and MR imaging from 41 consecutive patients with breast lesions (25 invasive ductal carcinoma, 3 fibroadenoma, 1 phyllodes tumor, 2 ductal hyperplasia, 2 primary malignant lymphoma, 3 mastopathy, 1 metastasis, 1 tubular adenoma, 1 ductal carcinoma in situ, 1 diabetic mastopathy, and 1 intraductal papilloma). In each patient, elastography images were classified based on Tsukuba ES. We calculated the ratio of signal intensity of the lesion to the muscle on short Tau inversion recovery images (L/M ratio), enhancement ratio of early to precontrast and early to delayed images, and ADC for each lesion. The ES and MR findings were correlated with the degree of fibrosis (based on Masson trichrome stain).

RESULTS: The ES significantly correlated with the L/M ratio (P = 0.0306) and the ADC (P = 0.0256). The stromal fibrosis also correlated with ES (P = 0.0023), the L/M ratio (P = 0.0344), and enhancement ratio of the early-to-delayed images (P = 0.049).

CONCLUSIONS: The ES and L/M ratio are correlated significantly with each other, and they are correlated with the fibrosis. These results suggest that they will provide the information on the fibrosis and may help the diagnosis of breast lesions.}, } @article {pmid25299107, year = {2014}, author = {Huan, JL and Gao, X and Xing, L and Qin, XJ and Qian, HX and Zhou, Q and Zhu, L}, title = {Screening for key genes associated with invasive ductal carcinoma of the breast via microarray data analysis.}, journal = {Genetics and molecular research : GMR}, volume = {13}, number = {3}, pages = {7919-7925}, doi = {10.4238/2014.September.29.5}, pmid = {25299107}, issn = {1676-5680}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal/*genetics ; Female ; *Genes, Neoplasm ; *Genetic Predisposition to Disease ; Humans ; Oligonucleotide Array Sequence Analysis ; }, abstract = {The aim of this study was to identify key genes related to invasive ductal carcinoma (IDC) of the breast by analyzing gene expression data with bioinformatic tools. Microarray data set GSE31138 was downloaded from Gene Expression Omnibus, including 3 breast cancer tissue samples and 3 normal controls. Differentially expressed genes (DEGs) between breast cancer and normal control were screened out (FDR < 0.05 and |logFC| > 2). Coexpression between genes was examined with String, and a network was then constructed. Relevant pathways and diseases were retrieved with KOBAS. A total of 56 DEGs were obtained in the IDC of the breast compared with normal controls. A gene coexpression network including 27 pairs of genes was constructed and all the genes in the network were upregulated. Further study indicated that most of the genes in the coexpression network were enriched in ECM-receptor interaction (COL4A2, FN1, and HMMR) and nucleotide excision repair (CETN2 and PCNA) pathways, and that the most significantly related disease was autoimmune lymphoproliferative syndromes. A number of DEGs were acquired through comparative analysis of gene expression data. These findings are beneficial in promoting the understanding of the molecular mechanisms in breast cancer. More importantly, some key genes were revealed via gene coexpression network analysis, which could be potential biomarkers for IDC of the breast.}, } @article {pmid25296604, year = {2014}, author = {Ross, M and Hadzikadic Gusic, L and Dabbs, DJ and Kelley, J and Diego, E}, title = {Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.}, journal = {Tumori}, volume = {100}, number = {4}, pages = {136e-9e}, doi = {10.1700/1636.17928}, pmid = {25296604}, issn = {2038-2529}, mesh = {Adult ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Arm ; Axilla ; Breast Neoplasms/diagnosis/*therapy ; Capecitabine ; Carcinoma, Ductal, Breast/*diagnosis/*therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/therapy ; Chemotherapy, Adjuvant ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage/analogs & derivatives ; Humans ; Interferons/administration & dosage ; *Lymph Node Excision ; Mammaplasty ; *Mastectomy, Segmental/methods ; Mastectomy, Simple ; Melanoma/*secondary ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/*therapy ; Neoplasms, Multiple Primary/*diagnosis/pathology/*therapy ; Patient Care Team ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/pathology/*therapy ; Skin Neoplasms/*pathology ; Trastuzumab ; }, abstract = {BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies.

CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant.

CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.}, } @article {pmid25296018, year = {2014}, author = {Beck, AP and Brooks, A and Zeiss, CJ}, title = {Invasive ductular carcinoma in 2 rhesus macaques (Macaca mulatta).}, journal = {Comparative medicine}, volume = {64}, number = {4}, pages = {314-322}, pmid = {25296018}, issn = {2769-819X}, mesh = {Animals ; Biomarkers, Tumor/analysis ; Biopsy/veterinary ; Carcinoma, Ductal, Breast/chemistry/pathology/surgery/*veterinary ; Female ; Immunohistochemistry/veterinary ; *Macaca mulatta ; Mammary Glands, Animal/chemistry/*pathology/surgery ; Mammary Neoplasms, Animal/chemistry/*pathology/surgery ; Mastectomy/veterinary ; Monkey Diseases/metabolism/*pathology/surgery ; Predictive Value of Tests ; }, abstract = {In the United States, breast cancer is the most common malignancy among women, with an estimated lifetime incidence of approximately 12% in American women. Invasive ductal carcinoma is the most common form of breast cancer in women, accounting for approximately 60% of all breast carcinomas. Prognostic markers are used to assess aggressiveness, invasiveness, and extent of spread of a neoplasm and thus may be correlated with patient survival. Immunohistochemistry is currently widely used for this purpose, with a variety of prognostication markers available. Classic markers for breast cancer in women include estrogen and progesterone receptor steroid hormone proteins and human epidermal growth factor receptor 2. Many additional markers have been used in diagnosis and prognostication, including p53, p63, and E-cadherin and cell proliferation markers such as Ki67. Despite an estimated lifetime incidence of approximately 6.1%, naturally occurring mammary neoplasms in nonhuman primates are uncommonly reported, with only sporadic references over the past 75 y. The majority of reported tumors occur in rhesus macaques, although this prevalence has been suggested to be a consequence of their high frequency of usage in biomedical research. Here we present 2 cases of mammary carcinoma in adult female intact rhesus macaques, with cytology, histopathology, and extensive immunohistochemical analysis. According to current classifications for human breast tumors, both tumors were classified as invasive ductal carcinoma. The prognostic value of immunohistochemical markers in human breast cancer and in reported cases in nonhuman primates is discussed.}, } @article {pmid25295098, year = {2014}, author = {Li, W and Song, M}, title = {Expression of multidrug resistance proteins in invasive ductal carcinoma of the breast.}, journal = {Oncology letters}, volume = {8}, number = {5}, pages = {2103-2109}, pmid = {25295098}, issn = {1792-1074}, abstract = {Chemotherapy is commonly used for the treatment of breast cancer. However, the resistance to chemotherapeutic agents, often mediated by multidrug resistance (MDR) mechanisms, is a common occurrence. The present study examined the expression of several MDR-related proteins (MRPs) in invasive ductal carcinoma (IDC) of the breast, and assessed their association with clinicopathological variables and their prognostic significance. In addition, immunohistochemistry was used to measure the expression of MRP, p-glycoprotein (P-gp), topoisomerase 2α (Topo2α), thymidylate synthase (TS) and glutathione-S-transferase π (GST-π) in 156 resected IDCs of the breast. Pearson's χ[2] test and Spearman's correlation coefficient were used to analyze the association between MDR protein expression and several clinicopathological variables. The association between each of the five MDR proteins was also examined. Furthermore, Kaplan-Meier analysis and Cox regression modeling were used to assess overall survival. The expression of MRP, P-gp, Topo2α, TS and GST-π was detected in 20.5% (32/156), 25.0% (39/156), 84.0% (131/156), 41.7% (65/156) and 41.0% (64/156) of cases examined, respectively. No correlation was identified between MRP and Topo-2α and the clinicopathological variables examined. By contrast, P-gp (χ[2]=20.226; P<0.0001) and GST-π (χ[2]=35.032; P<0.0001) were found to positively correlate with tumor grade. In addition, staining for TS was associated with axillary lymph node metastasis (χ[2]=42.281; P<0.0001). The expression levels of P-gp and GST-π were found to be significantly correlated (r= 0.319; P<0.0001). Furthermore, GST-π expression was elevated in estrogen receptor-negative breast cancer (χ[2]=17.407; P<0.0001). Tumor histological grade, in addition to TS and GST-π expression, were significant predictors of a poor survival outcome. TS and GST-π are consequently useful prognostic biomarkers in IDC, therefore, when establishing a personalized chemotherapeutic plan, the expression of MDR proteins must be considered.}, } @article {pmid25291865, year = {2014}, author = {Cinocca, S and Rosini, F and Asioli, S and Del Vecchio, M and Cucchi, MC and Saguatti, G and Betts, CM and Foschini, MP}, title = {Cytological features of nipple adenoma in scraping smears.}, journal = {Pathologica}, volume = {106}, number = {2}, pages = {41-44}, pmid = {25291865}, issn = {0031-2983}, mesh = {Adenoma/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Diagnosis, Differential ; Female ; Humans ; Nipples/*pathology ; Predictive Value of Tests ; Prognosis ; Specimen Handling/*methods ; }, abstract = {INTRODUCTION: Nipple adenoma (NA) is a benign epithelial lesion of the breast that can clinically simulate Paget's disease or invasive ductal carcinoma. Therefore, correct pre-operative diagnosis is important for appropriate management.

METHODS: Cytological samples may be obtained by different methods such as fine needle aspiration, nipple discharge or nipple scraping. Herein, the cytological features of three cases of NA are described in which samples were derived from nipple scraping.

RESULTS: In all three cases, patients were adult females presenting with a sub-areolar nodule, showing skin ulceration in 2 of 3 cases. The nipple scraping cytological smears were characterised by a bloody background with epithelial cells arranged in clusters or singularly, showing an irregular nuclei profile. These features could simulate a malignant process. However, at higher magnification, fine nuclear chromatin with inconspicuous nucleoli and presence of myoepithelial cells were helpful to exclude malignancy.

DISCUSSION: NA may present "worrisome" cytological features on smears derived from nipple scraping. Therefore, knowledge of the cytological spectrum of this lesion is important to avoid misdiagnosis.}, } @article {pmid25287760, year = {2015}, author = {Abomaray, FM and Al Jumah, MA and Kalionis, B and AlAskar, AS and Al Harthy, S and Jawdat, D and Al Khaldi, A and Alkushi, A and Knawy, BA and Abumaree, MH}, title = {Human Chorionic Villous Mesenchymal Stem Cells Modify the Functions of Human Dendritic Cells, and Induce an Anti-Inflammatory Phenotype in CD1+ Dendritic Cells.}, journal = {Stem cell reviews and reports}, volume = {11}, number = {3}, pages = {423-441}, pmid = {25287760}, issn = {2629-3277}, mesh = {Antigens, CD1/metabolism ; Cell Differentiation/drug effects/*genetics ; Cell Proliferation/genetics ; Chorionic Villi/metabolism ; Coculture Techniques ; Dendritic Cells/*cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage ; Humans ; Interleukin-4/administration & dosage ; Mesenchymal Stem Cells/*cytology/metabolism ; Monocytes/*cytology/metabolism ; Placenta/cytology/metabolism ; Pregnancy ; }, abstract = {BACKGROUND: Mesenchymal stem cells derived from the chorionic villi of human term placenta (pMSCs) have drawn considerable interest because of their multipotent differentiation potential and their immunomodulatory capacity. These properties are the foundation for their clinical application in the fields of stem cell transplantation and regenerative medicine. Previously, we showed that pMSCs induce an anti-inflammatory phenotype in human macrophages. In this study, we determined whether pMSCs modify the differentiation and maturation of human monocytes into dendritic cells (DCs). The consequences on dendritic function and on T cell proliferation were also investigated.

METHODS: Interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to stimulate the differentiation of monocytes into immature dendritic cells (iDCs), which were subsequently co-cultured with pMSCs. Lipopolysaccharide (LPS) was used to induce maturation of iDCs into mature dendritic cells (mDCs). Flow cytometry and enzyme-linked immunosorbent assays (ELISA) were used to quantify the effect pMSC co-culturing on DC differentiation using CD1a, a distinctive marker of DCs, as well as other molecules important in the immune functions of DCs. The phagocytic activity of iDCs co-cultured with pMSCs, and the effects of iDCs and mDC stimulation on T cell proliferation, were also investigated.

RESULTS: Monocyte differentiation into iDCs was inhibited when co-cultured with pMSCs and maturation of iDCs by LPS treatment was also prevented in the presence of pMSCs as demonstrated by reduced expression of CD1a and CD83, respectively. The inhibitory effect of pMSCs on iDC differentiation was dose dependent. In addition, pMSC co-culture with iDCs and mDCs resulted in both phenotypic and functional changes as shown by reduced expression of costimulatory molecules (CD40, CD80, CD83 and CD86) and reduced capacity to stimulate CD4(+) T cell proliferation. In addition, pMSC co-culture increased the surface expression of major histocompatibility complex (MHC-II) molecules on iDCs but decreased MHC-II expression on mDCs. Moreover, pMSC co-culture with iDCs or mDCs increased the expression of immunosuppressive molecules [B7H3, B7H4, CD273, CD274 and indoleamine-pyrrole 2,3-dioxygenase (IDO). Additionally, the secretion of IL-12 and IL-23 by iDCs and mDCs co-cultured with pMSCs was decreased. Furthermore, pMSC co-culture with mDCs decreased the secretion of IL-12 and INF-γ whilst increasing the secretion of IL-10 in a T cell proliferation experiment. Finally, pMSC co-culture with iDCs induced the phagocytic activity of iDCs.

CONCLUSIONS: We have shown that pMSCs have an inhibitory effect on the differentiation, maturation and function of DCs, as well as on the proliferation of T cells, suggesting that pMSCs can control the immune responses at multiple levels.}, } @article {pmid25287438, year = {2015}, author = {Adrada, BE and Huo, L and Lane, DL and Arribas, EM and Resetkova, E and Yang, W}, title = {Histopathologic correlation of residual mammographic microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer.}, journal = {Annals of surgical oncology}, volume = {22}, number = {4}, pages = {1111-1117}, doi = {10.1245/s10434-014-4113-8}, pmid = {25287438}, issn = {1534-4681}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/diagnostic imaging/drug therapy/*pathology ; Calcinosis/chemically induced/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/drug therapy/*pathology ; Carcinoma, Lobular/diagnostic imaging/drug therapy/*pathology ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasm, Residual/chemically induced/diagnostic imaging/*pathology ; Prognosis ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: This study was designed to determine the histopathologic correlation at surgery of residual mammographic calcifications in patients after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC).

METHODS: This single-institution, retrospective study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability act compliant. Women with LABC who underwent NAC between January 1, 2004 and December 31, 2008 and had mammography performed before and after NAC available for review were included in this study. The extent of microcalcifications associated with cancer before and after the completion of NAC was correlated with histopathology and biomarker status.

RESULTS: Of 494 patients who met the inclusion criteria, 106 demonstrated microcalcifications on pre-, post-chemotherapy, or both sets of mammograms and were included in this study. Of 106 women, 31 (29 %) had invasive ductal carcinoma (IDC) and 60 (57 %) had both IDC and ductal carcinoma in situ (DCIS). Microcalcifications decreased or remained stable in 76 (72 %) patients after completion of NAC. Correlation of microcalcifications with histopathology after NAC showed that 43 (40.6 %) patients had tumors associated with benign pathology. Of 32 patients with pathologic complete response, calcifications were associated with DCIS in 9 (9 %) and benign findings in 21 (22 %). The proportion of residual malignant calcifications was higher in ER+ versus ER- patients after NAC.

CONCLUSIONS: The extent of calcifications on mammography following NAC does not correlate with the extent of residual disease in up to 22 % of women; this information may impact surgical planning in subsets of women with breast cancer.}, } @article {pmid25283075, year = {2015}, author = {Engstrøm, MJ and Opdahl, S and Vatten, LJ and Haugen, OA and Bofin, AM}, title = {Invasive lobular breast cancer: the prognostic impact of histopathological grade, E-cadherin and molecular subtypes.}, journal = {Histopathology}, volume = {66}, number = {3}, pages = {409-419}, pmid = {25283075}, issn = {1365-2559}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology ; Cadherins/analysis/*biosynthesis ; Carcinoma, Ductal, Breast/mortality/pathology ; Carcinoma, Lobular/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Prognosis ; Proportional Hazards Models ; }, abstract = {AIMS: The aim of this study was to compare breast cancer specific survival (BCSS) for invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and, further, to evaluate critically the prognostic value of histopathological grading of ILC and examine E-cadherin as a prognostic marker in ILC.

METHODS AND RESULTS: The study comprised 116 lobular and 611 ductal breast carcinomas occurring between 1961 and 2008. All cases had been classified previously according to histopathological type and grade, stained for oestrogen receptor (ER), progesterone receptor (PR), antigen Ki67 (Ki67), epithelial growth factor receptor (EGFR), cytokeratin 5 (CK5) and human epidermal growth factor receptor 2 (HER2) and classified into molecular subtypes. For the present study, immunohistochemical staining for E-cadherin was performed. The Kaplan-Meier method and Cox proportional hazards models were used in the analyses. Grade 2 tumours comprised 85.3% of the lobular tumours and 51.9% of the ductal tumours. BCSS in ILC grade 2 was comparable to that of IDC grade 3. E-cadherin-negative ILC had a poorer prognosis compared to E-cadherin positive ILC and to IDC regardless of E-cadherin status.

CONCLUSIONS: The implication of histopathological grading may differ in ILC compared to IDC. E-cadherin may be useful in prognostication in ILC and thereby influence the determination of treatment strategies for this group of women.}, } @article {pmid25282709, year = {2014}, author = {Taneja, S and Jena, A and Goel, R and Sarin, R and Kaul, S}, title = {Simultaneous whole-body [18]F-FDG PET-MRI in primary staging of breast cancer: a pilot study.}, journal = {European journal of radiology}, volume = {83}, number = {12}, pages = {2231-2239}, doi = {10.1016/j.ejrad.2014.09.008}, pmid = {25282709}, issn = {1872-7727}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*diagnosis ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/pathology ; *Magnetic Resonance Imaging ; Middle Aged ; Multimodal Imaging ; Neoplasm Staging ; Pilot Projects ; *Positron-Emission Tomography ; Radiopharmaceuticals ; Retrospective Studies ; Whole Body Imaging ; }, abstract = {PURPOSE: Accurate initial staging in breast carcinoma is important for treatment planning and for establishing the likely prognosis. The purpose of this study was to assess the utility of whole body simultaneous (18)F-FDG PET-MRI in initial staging of breast carcinoma.

METHODS: 36 patients with histologically confirmed invasive ductal carcinoma underwent simultaneous whole body (18)F-FDG PET-MRI on integrated 3T PET-MR scanner (Siemens Biograph mMR) for primary staging. Primary lesion, nodes and metastases were evaluated on PET, MRI and PET-MRI for lesion count and diagnostic confidence (DC). Kappa co relation analysis was done to assess agreement between the satellite, nodal and metastatic lesions detected by PET and MRI. Histopathology, clinical/imaging follow-up served as the reference standard.

RESULTS: 36 patients with 37 histopathologically proven index breast cancer were retrospectively studied. Of 36 patients, 25 patients underwent surgery and 11 patients received systemic therapy. All index cancers were seen on PET and MR. Fused PET-MRI showed highest diagnostic confidence score of 5 as compared to PET (median 4; range 3-5) and MRI (median 4; range 4-5) alone. 2/36 (5.5%) patients were detected to have unsuspected contralateral synchronous cancer. 47 satellite lesions were detected on DCE MRI of which 23 were FDG avid with multifocality and multicentricity in 21 (58%) patients. Kappa co relation analysis revealed fair agreement for satellite lesion detection by the two modalities (κ=0.303; P=0.003). The study showed a sensitivity of 60% and 93.3% on PET and MRI respectively for detection of axillary lymph nodes with a specificity of 91% for both and a false negative rate of 6.7% on MRI and 40% on PET. Kappa co relation analysis between PET and MRI for all the lymph nodes detected revealed fair agreement by the two modalities (κ=0.337; P=0.000). Combined PET-MRI increased diagnostic confidence for nodal involvement (median DC 5, range 4-5; P<0.05). Distant metastases were found in 8/36 (22%) patients at the time of diagnosis with a total of 91 metastatic lesions on PET (DC≥4) and 105 on MRI (DC≥4), the difference being statistically significant (P=0.001) while Kappa co relation analysis showed significant agreement between the two modalities (κ=0.667; P=0.000). Overall PET-MRI led to a change in management in 12 (33.3%) patients.

CONCLUSION: In this pilot study, simultaneous (18)F-FDG PET-MR, has been found to be useful in whole-body initial staging of breast cancer patients.}, } @article {pmid25278000, year = {2015}, author = {Nakano, SJ and Miyamoto, SD and Movsesian, M and Nelson, P and Stauffer, BL and Sucharov, CC}, title = {Age-related differences in phosphodiesterase activity and effects of chronic phosphodiesterase inhibition in idiopathic dilated cardiomyopathy.}, journal = {Circulation. Heart failure}, volume = {8}, number = {1}, pages = {57-63}, pmid = {25278000}, issn = {1941-3297}, support = {R21 HL097123/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; T32 HL007822/HL/NHLBI NIH HHS/United States ; R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Blotting, Western ; Cardiomyopathy, Dilated/drug therapy/*enzymology/physiopathology ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Myocardial Contraction/physiology ; Phosphodiesterase 3 Inhibitors/*therapeutic use ; Phosphoric Diester Hydrolases/*blood/drug effects ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Despite the application of proven adult heart failure therapies to children with idiopathic dilated cardiomyopathy (IDC), prognosis remains poor. Clinical experience with phosphodiesterase 3 inhibitors (PDE3i) in pediatric patients with IDC, however, demonstrates improved heart failure symptoms without the increased incidence of sudden death seen in adults treated with PDE3i. We sought to determine age-related differences in PDE activity and associated intracellular signaling responsible for the efficacy and relative safety of chronic PDE3i in pediatric heart failure.

METHODS AND RESULTS: cAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) were determined in explanted human left ventricular myocardium (pediatric n=41; adult n=88). Adults and children with IDC (not treated with PDE3i) had lower cAMP and pPLB compared with nonfailing controls. In contrast to their adult counterparts, pediatric IDC patients chronically treated with PDE3i had elevated cAMP (P=0.0403) and pPLB (P=0.0119). In addition, total PDE- and PDE3-specific activities were not altered in pediatric IDC patients on PDE3i, whereas adult IDC patients on PDE3i demonstrated higher total PDE-specific (74.6±13.8 pmol/mg per minute) and PDE3-specific (48.2±15.9 pmol/mg per minute) activities in comparison with those of nonfailing controls (59.5±14.4 and 35.5±12.8 pmol/mg per minute, respectively).

CONCLUSIONS: Elevated cAMP and higher pPLB may contribute to sustained hemodynamic benefits in pediatric IDC patients treated with PDE3i. In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i may perpetuate lower myocardial cAMP and pPLB levels, limiting the potential benefits of PDE3i therapy.}, } @article {pmid25276795, year = {2014}, author = {Smith, D and Kong, F and Yang, D and Larson, R and Sims-Mourtada, J and Woodward, WA}, title = {Patched targeting peptides for imaging and treatment of hedgehog positive breast tumors.}, journal = {BioMed research international}, volume = {2014}, number = {}, pages = {525680}, pmid = {25276795}, issn = {2314-6141}, support = {R01 CA138230-01/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; 8 P20 GM103446-13/GM/NIGMS NIH HHS/United States ; U54-GM104941/GM/NIGMS NIH HHS/United States ; P20 GM103446/GM/NIGMS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Breast Neoplasms/*diagnosis/*drug therapy ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cysteine/analogs & derivatives ; *Diagnostic Imaging ; Female ; Hedgehog Proteins/*metabolism ; Humans ; Molecular Sequence Data ; Molecular Targeted Therapy ; Patched Receptors ; Patched-1 Receptor ; Peptides/chemistry/pharmacology/*therapeutic use ; Rats, Inbred F344 ; Receptors, Cell Surface/*metabolism ; Spheroids, Cellular/drug effects/pathology ; Staining and Labeling ; Technetium ; Xenograft Model Antitumor Assays ; }, abstract = {High tumor hedgehog expression is correlated with poor prognosis in invasive ductal carcinoma. Peptides which bind the patched receptor have recently been reported to have a growth inhibitory effect in tumors with activated hedgehog signaling. We sought to examine growth inhibition with these peptides in breast cancer cells and use these peptides as molecular imaging probes to follow changes in hedgehog expression after chemotherapy. Significant growth inhibition was observed in breast cancer cell lines treated with PTCH-blocking peptides. Significant in vitro uptake was observed with both FITC- and (99m)Tc-EC-peptide conjugates. In vivo imaging studies displayed greater accumulation of (99m)Tc-labeled peptides within tumors as compared to adjacent muscle tissue. Patched receptor expression increased after treatment and this correlated with an increase in tumor radiotracer uptake. These studies suggest that peptides which bind the sonic hedgehog docking site in patched receptor correlate with patched expression and can be used to image patched in vivo. Further, our data suggest that radiolabeled peptides may enable us to examine the activity of the hedgehog signaling pathway and to evaluate response to anti-cancer therapies.}, } @article {pmid25276390, year = {2014}, author = {Liao, Y and Chen, KH and Huang, GY and Song, W}, title = {Pulmonary arteriovenous malformations presenting as refractory heart failure.}, journal = {Journal of thoracic disease}, volume = {6}, number = {9}, pages = {E169-72}, pmid = {25276390}, issn = {2072-1439}, abstract = {A 22-year-old young man with a history of idiopathic dilated cardiomyopathy (IDC) was admitted to our hospital due to difficult-to-control heart failure. A thoracic X-ray showed multiple nodules at the both pulmonary hilus and upper lobe of the right lung. Computed tomography (CT) angiography of the thorax confirmed arteriovenous malformation (AVM). However, effective treatment was impossible due to the poor physical condition; he died a few days later. Here we reported on the case of pulmonary arteriovenous malformations (PAVMs) being misdiagnosed as refractory heart failure.}, } @article {pmid25271877, year = {2015}, author = {Barbosa, OV and Reiriz, AB and Boff, RA and Oliveira, WP and Rossi, L}, title = {Angiosarcoma in previously irradiated breast in patient with Li-Fraumeni syndrome. A case report.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {133}, number = {2}, pages = {151-153}, pmid = {25271877}, issn = {1806-9460}, mesh = {Adult ; Breast Neoplasms/etiology/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*radiotherapy ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Hemangiosarcoma/*etiology/pathology ; Humans ; Li-Fraumeni Syndrome/*genetics/pathology ; *Neoplasms, Radiation-Induced/pathology ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {CONTEXT: Li-Fraumeni syndrome is a rare disease with an autosomal dominant inheritance pattern and high penetrance that defines a 50% chance of developing cancer before the age of 30 years, including cases of breast sarcoma. Patients with this syndrome who require radiotherapy have an increased risk of developing secondary malignancies including angiosarcomas.

CASE REPORT: This was a case report on a female patient with Li-Fraumeni syndrome. In October 2005, she was diagnosed with invasive ductal carcinoma of the right breast and underwent sectorectomy. She then received chemotherapy and adjuvant radiotherapy. Trastuzumab and tamoxifen were also part of the treatment. She recently sought care at our hospital, complaining of hyperemia and nodulation in the right breast, and underwent surgical resection that revealed epithelioid angiosarcoma.

CONCLUSIONS: When genetic predisposition due to Li-Fraumeni syndrome is documented, the therapy should be adapted so as to minimize the risk. Thus, conservative surgical treatments should be avoided and mastectomy without radiation should be prioritized. In cases in which use of radiotherapy is justified, patients should be followed up intensively.}, } @article {pmid25270118, year = {2014}, author = {Pacheco-Velázquez, SC and Gallardo-Pérez, JC and Aguilar-Ponce, JL and Villarreal, P and Ruiz-Godoy, L and Pérez-Sánchez, M and Marín-Hernández, A and Ruiz-García, E and Meneses-García, A and Moreno-Sánchez, R and Rodríguez-Enríquez, S}, title = {Identification of a metabolic and canonical biomarker signature in Mexican HR+/HER2-, triple positive and triple-negative breast cancer patients.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2549-2559}, doi = {10.3892/ijo.2014.2676}, pmid = {25270118}, issn = {1791-2423}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Estrogen Receptor alpha/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis ; Mexico ; Middle Aged ; Prognosis ; *Proteomics ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/*genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/diagnosis/*genetics/pathology ; }, abstract = {Infiltrating ductal breast cancer (IDC) is the principal tumor associated-malignancy in Mexican women. In IDC, the development of intermittent hypoxia leads to an adaptive response coordinated by the transcriptional factor HIF-1α. In the present pilot, retrospective/cross-sectional study, the HIF-1α expression was analyzed in 102 tru-cut biopsies from female patients (51 ± 12 years) without previous clinical treatment and compared to 31 normal breast biopsies. The 102 IDC samples corresponded to 56% of HER2-/HR+; 8% of HER2+/HR-; 22% of triple positive (HER2+/HR+); and 14% of triple negative (TN, HER2-/HR-) subtypes. To assess HIF-1α functionality, proteomic and kinetic analysis of glycolytic as well as mitochondrial enzymes, were determined. Validation of HIF-1α as cancer biomarker was assessed by determining the contents of the commonly used biomarkers c-MYC, Ki67, and H- and K-RAS, as well as metastatic and autophagy proteins. Proteomic analysis revealed that HIF-1α, c-MYC, HER2 and COXIV contents were significantly increased in all IDC subtypes vs. normal tissue. The contents and activities of glycolytic proteins were similar between normal and IDC samples, except for HER2-/HR+ where a substantial increase of HKII was observed. Significant increase in 2OGDH and E-cadherin was detected for TN samples vs. other IDC subtypes and for normal samples. These results clearly indicated that HIF-1α + COXIV + c-MYC (+ HER2 for HER2+ subtype) may be useful to depict a breast cancer metabolic marker pattern for diagnosis, whereas the contents of HIF-1α + c-MYC + 2OGDH + E-cadherin may be an alternative useful and reliable signature for TN subtype cancer prognosis.}, } @article {pmid25267099, year = {2014}, author = {Pandya, HJ and Chen, W and Goodell, LA and Foran, DJ and Desai, JP}, title = {Mechanical phenotyping of breast cancer using MEMS: a method to demarcate benign and cancerous breast tissues.}, journal = {Lab on a chip}, volume = {14}, number = {23}, pages = {4523-4532}, pmid = {25267099}, issn = {1473-0189}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; R01 LM009239/LM/NLM NIH HHS/United States ; R01 CA156386/CA/NCI NIH HHS/United States ; R01 CA161375/CA/NCI NIH HHS/United States ; R01CA161375/CA/NCI NIH HHS/United States ; }, mesh = {Breast/*chemistry ; Breast Neoplasms/*chemistry/classification ; Carcinoma, Ductal, Breast/chemistry ; Female ; Humans ; Micro-Electrical-Mechanical Systems/*methods ; Microscopy, Electron, Scanning ; Phenotype ; Tissue Array Analysis/*methods ; }, abstract = {The mechanical properties of tissue change significantly during the progression from healthy to malignant. Quantifying the mechanical properties of breast tissue within the tumor microenvironment can help to delineate benign from cancerous stages. In this work, we study high-grade invasive ductal carcinoma in comparison with their matched tumor adjacent areas, which exhibit benign morphology. Such paired tissue cores obtained from eight patients were indented using a MEMS-based piezoresistive microcantilever, which was positioned within pre-designated epithelial and stromal areas of the specimen. Field emission scanning electron microscopy studies on breast tissue cores were performed to understand the microstructural changes from benign to malignant. The normal epithelial tissues appeared compact and organized. The appearance of cancer regions, in comparison, not only revealed increased cellularity but also showed disorganization and increased fenestration. Using this technique, reliable discrimination between epithelial and stromal regions throughout both benign and cancerous breast tissue cores was obtained. The mechanical profiling generated using this method has the potential to be an objective, reproducible, and quantitative indicator for detecting and characterizing breast cancer.}, } @article {pmid25265904, year = {2014}, author = {Srivastava, G and Assi, J and Kashat, L and Matta, A and Chang, M and Walfish, PG and Ralhan, R}, title = {Nuclear Ep-ICD accumulation predicts aggressive clinical course in early stage breast cancer patients.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {726}, pmid = {25265904}, issn = {1471-2407}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cell Adhesion Molecules/*metabolism ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Disease-Free Survival ; Epithelial Cell Adhesion Molecule ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: Regulated intramembrane proteolysis of Epithelial cell adhesion molecule (EpCAM) results in release of its intracellular domain (Ep-ICD) which triggers oncogenic signalling. The clinical significance of Ep-ICD in breast cancer remains to be determined. Herein, we examined the expression of nuclear and cytoplasmic Ep-ICD, and membranous extracellular domain of EpCAM (EpEx) in breast cancer patients, to determine its potential utility in predicting aggressive clinical course of the disease.

METHODS: In this retrospective study, 266 breast cancers and 45 normal breast tissues were immunohistochemically analyzed to determine the expression patterns of nuclear and cytoplasmic Ep-ICD and membranous EpEx and correlated with clinicopathological parameters and follow up. Disease-free survival was determined by Kaplan-Meier method and multivariate Cox regression analysis.

RESULTS: Nuclear Ep-ICD was more frequently expressed in breast cancers compared to normal tissues. Significant association was observed between increased nuclear Ep-ICD expression and reduced disease-free survival in patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) (p < 0.001). Nuclear Ep-ICD was positive in all the 13 DCIS and 25 IDC patients who had reduced disease-free survival, while none of the nuclear Ep-ICD negative DCIS or IDC patients had recurrence during the follow up period. Notably, majority of IDC patients who had recurrence had early stage tumors. Multivariate Cox regression analysis identified nuclear Ep-ICD as the most significant predictive factor for reduced disease-free survival in IDC patients (p = 0.011, Hazard ratio = 80.18).

CONCLUSION: Patients with nuclear Ep-ICD positive breast cancers had poor prognosis. The high recurrence of disease in nuclear Ep-ICD positive patients, especially those with early tumor stage suggests that nuclear Ep-ICD accumulation holds the promise of identifying early stage patients with aggressive disease who are likely to be in need of more rigorous post-operative surveillance and/or treatment.}, } @article {pmid25263387, year = {2014}, author = {Iczkowski, KA and Egevad, L and Ma, J and Harding-Jackson, N and Algaba, F and Billis, A and Camparo, P and Cheng, L and Clouston, D and Comperat, EM and Datta, MW and Evans, AG and Griffiths, DF and Guo, CC and Hailemariam, S and Huang, W and Humphrey, PA and Jiang, Z and Kahane, H and Kristiansen, G and La Rosa, FG and Lopez-Beltran, A and MacLennan, GT and Magi-Galluzzi, C and Merrimen, J and Montironi, R and Osunkoya, AO and Picken, MM and Rao, N and Shah, RB and Shanks, JH and Shen, SS and Tawfik, OW and True, LD and Van der Kwast, T and Varma, M and Wheeler, TM and Zynger, DL and Sahr, N and Bostwick, DG}, title = {Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.}, journal = {Annals of diagnostic pathology}, volume = {18}, number = {6}, pages = {333-342}, doi = {10.1016/j.anndiagpath.2014.08.010}, pmid = {25263387}, issn = {1532-8198}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*pathology ; Diagnosis, Differential ; Health Surveys ; Humans ; Male ; Neoplasm Grading ; Observer Variation ; Physicians ; Prognosis ; Prostatic Intraepithelial Neoplasia/pathology ; Prostatic Neoplasms/*pathology ; Reproducibility of Results ; }, abstract = {The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.}, } @article {pmid25261651, year = {2014}, author = {Petekkaya, I and Aksoy, S and Roach, EC and Okoh, AK and Gecmez, G and Gezgen, G and Isler, DC and Dogan, E and Babacan, T and Sarici, F and Petekkaya, E and Altundag, K}, title = {Impact of inflammatory markers on the prognosis of patients with operable breast cancer.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {19}, number = {3}, pages = {673-680}, pmid = {25261651}, issn = {1107-0625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Sedimentation ; Breast Neoplasms/blood/*mortality ; C-Reactive Protein/analysis ; Female ; Ferritins/blood ; Humans ; Inflammation/*complications ; L-Lactate Dehydrogenase/blood ; Middle Aged ; Prognosis ; Serum Albumin/analysis ; beta 2-Microglobulin/blood ; }, abstract = {PURPOSE: To investigate the effect of inflammatory markers on the prognosis of patients with operable breast cancer.

METHODS: This study was conducted on breast cancer patients followed up between December 2009 and December 2012 at the Division of Medical Oncology, Department of Internal Medicine, Hacettepe University Medical School. A total of 704 patients with stages I to III disease whose inflammatory markers were assessed at the time of diagnosis were included the study. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, ferritin, β2 microglobulin (β2-M), and lactate dehydrogenase (LDH) levels were evaluated as inflammatory markers.

RESULTS: The median age at diagnosis was 50 years (range 25-92). Of the patients 42.8% were premenopausal and 48.2 % postmenopausal. Invasive ductal carcinoma was the most common histology (76.5 %). Serum ferritin, LDH, β2-M, ESR, and CRP were higher than the normal values in 1.0, 4.3, 9.5, 32.4 and 36.4 % of the patients, respectively. Serum albumin levels were lower than the normal values in 1.7 % of the patients. The median patient follow-up period was 22 months (range 3-227). During follow-up, metastatic disease developed in 31 patients (4.4%) and 11 patients (1.56%) died due to disease progression. Two-year overall survival (OS) and disease free survival (DFS) rates were not statistically different among patients with normal and abnormal values with respect to albumin, ferritin, LDH, β2-M, CRP, and ESR.

CONCLUSION: Our study is the first study to investigate the effect of inflammatory markers on the prognosis of operable breast cancer patients. We showed that inflammatory markers such as ESR, CRP, ferritin, β2-M, albumin and LDH have no effect on prognosis.}, } @article {pmid25260852, year = {2015}, author = {Moccia, M and Mosca, L and Erro, R and Cervasio, M and Allocca, R and Vitale, C and Leonardi, A and Caranci, F and Del Basso-De Caro, ML and Barone, P and Penco, S}, title = {Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features.}, journal = {Neurobiology of aging}, volume = {36}, number = {1}, pages = {547.e5-11}, doi = {10.1016/j.neurobiolaging.2014.08.021}, pmid = {25260852}, issn = {1558-1497}, mesh = {Adult ; Aged ; Animals ; CADASIL/*genetics ; *Codon, Nonsense ; Exons/genetics ; Female ; Humans ; Italy ; Male ; Mice ; Middle Aged ; RNA, Messenger ; Receptor, Notch3 ; Receptors, Notch/*genetics ; Signal Transduction/genetics/physiology ; Young Adult ; }, abstract = {The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.}, } @article {pmid25257596, year = {2015}, author = {Zhang, M and Zhou, J and Wang, J and Zhou, Q and Fang, J and Zhou, C and Chen, W}, title = {Superparamagnetic iron oxide labeling limits the efficacy of rabbit immature dendritic cell vaccination by decreasing their antigen uptake ability in a lysosome-dependent manner.}, journal = {Biotechnology letters}, volume = {37}, number = {2}, pages = {289-298}, doi = {10.1007/s10529-014-1681-4}, pmid = {25257596}, issn = {1573-6776}, mesh = {Animals ; Aspirin ; Autophagy/drug effects ; Cell Survival/drug effects ; Dendritic Cells/*drug effects/metabolism ; Lysosomes/*drug effects/metabolism ; Magnetite Nanoparticles/*chemistry/toxicity ; Rabbits ; Vaccination ; }, abstract = {Immature dendritic cells (iDCs) are for cell transplantation; however, no method has yet been developed for in vivo monitoring the transplanted iDCs. We have explored the feasibility of using superparamagnetic iron oxide (SPIO) labeling and magnetic resonance imaging for in vivo tracking of transplanted iDCs and determined the effects of SPIO labeling on iDC vaccination. With up to 50 μg Fe/ml, SPIO effectively labeled the iDCs without affecting their growth. At or above 100 μg Fe/ml, SPIO caused considerable damage to iDCs. SPIO labeling resulted in autophagosome formation and decreased the uptake of oxidized low density lipoprotein (ox-LDL), an exogenous antigen, by iDCs. SPIO and ox-LDL both localized to the lysosomes, and this competition for lysosomes could be partially responsible for the decreased ox-LDL phagocytic capacity of iDCs due to SPIO labeling.}, } @article {pmid25253827, year = {2014}, author = {Sankaye, P and Chhatani, S and Porter, G and Steel, J and Doyle, S}, title = {Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {33}, number = {10}, pages = {1805-1810}, doi = {10.7863/ultra.33.10.1805}, pmid = {25253827}, issn = {1550-9613}, mesh = {Axilla/*diagnostic imaging/pathology ; Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Humans ; Lymphatic Metastasis/*diagnostic imaging/pathology ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging/pathology ; Neoplasm Staging ; Retrospective Studies ; Ultrasonography, Interventional ; }, abstract = {OBJECTIVES: The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer.

METHODS: Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes.

RESULTS: Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups.

CONCLUSIONS: We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC.}, } @article {pmid25252956, year = {2014}, author = {Ellegård, R and Crisci, E and Burgener, A and Sjöwall, C and Birse, K and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 results in decreased antiviral and inflammatory responses in immature dendritic cells via CR3.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {193}, number = {9}, pages = {4590-4601}, pmid = {25252956}, issn = {1550-6606}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Complement System Proteins/*immunology ; Dendritic Cells/*immunology/*metabolism/virology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Profiling ; HIV Infections/genetics/*immunology/metabolism ; HIV-1/*immunology ; Humans ; Immunity, Innate/genetics ; Inflammation/genetics/immunology/metabolism ; Interferon Regulatory Factor-1/metabolism ; Interferon Regulatory Factor-3/metabolism ; Macrophage-1 Antigen/*metabolism ; Models, Biological ; NF-kappa B/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Protein Transport ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Toll-Like Receptor 8/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; src-Family Kinases/metabolism ; }, abstract = {Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-β, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1β, IL-6, and TNF-α, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-κB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.}, } @article {pmid25250186, year = {2014}, author = {Bredfeldt, JS and Liu, Y and Conklin, MW and Keely, PJ and Mackie, TR and Eliceiri, KW}, title = {Automated quantification of aligned collagen for human breast carcinoma prognosis.}, journal = {Journal of pathology informatics}, volume = {5}, number = {1}, pages = {28}, pmid = {25250186}, issn = {2229-5089}, support = {R01 CA114462/CA/NCI NIH HHS/United States ; R01 CA136590/CA/NCI NIH HHS/United States ; T32 CA009206/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS) are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts.

METHODS: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries.

RESULTS: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction.

CONCLUSION: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.}, } @article {pmid25250143, year = {2014}, author = {Taghizadeh-Kermani, A and Jafarian, AH and Ashabyamin, R and Seilanian-Toosi, M and Pourali, L and Asadi, M and Mashhadi, L}, title = {The Stromal Overexpression of CD10 in Invasive Breast Cancer and its Association with Clincophathologic Factors.}, journal = {Iranian journal of cancer prevention}, volume = {7}, number = {1}, pages = {17-21}, pmid = {25250143}, issn = {2008-2398}, abstract = {BACKGROUND: Breast carcinoma is the most common non-skin malignancy in women. More recently, it has been suggested that extracellular proteinase has also regulated growth factors and cytokines that might contribute to tumor progression. CD10 is a 90-110kd cell surface zinc-dependent metalloproteinase. Since CD10 is structurally similar to matrix metalloproteinase and stromelysin, it might facilitate cancer cell invasion and/or metastasis. The aim of this study was investigation the rate of CD10 expression in the stromal cells of invasive ductal breast carcinomas, Immunohistochemical aspects, then any other aspects to be able to clarify its correlation with other clinicopathological factors of this disease.

METHODS: One hundred patients with histopathologic diagnosis of invasive ductal carcinoma and 50 patients with fibroadenoma of breast (as the control group) have selected, then 150 paraffin blocks have obtained. The stained slides by immunohistochemistry method for CD10 marker have examined separately by two pathologists, and discrepancies have reviewed in common session to get the final result.

RESULTS: Stromal CD10 has detected in 28% of the IDC. No kind of immunoreactivity has identified in the stromal cells of normal breast. Stromal CD10 expression in IDC has significantly correlated with increasing tumor size (p<0.001), increasing histologic grade (p<0.001), the presence of nodal metastases (p<0.001) and estrogen receptor negative status (p=0.003).

CONCLUSION: Stromal CD10 expression in IDC has closely correlated with invasion and metastasis and it might play an important role in the pathogenesis of IDC.}, } @article {pmid25246039, year = {2014}, author = {Nasie, M and Bar-Tal, D and Pliskin, R and Nahhas, E and Halperin, E}, title = {Overcoming the barrier of narrative adherence in conflicts through awareness of the psychological bias of naïve realism.}, journal = {Personality & social psychology bulletin}, volume = {40}, number = {11}, pages = {1543-1556}, doi = {10.1177/0146167214551153}, pmid = {25246039}, issn = {1552-7433}, mesh = {Adult ; *Attitude ; Awareness ; *Conflict, Psychological ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Negotiating/psychology ; Social Identification ; Social Perception ; Young Adult ; }, abstract = {One significant socio-psychological barrier for peaceful resolution of conflicts is each party's adherence to its own collective narrative. We hypothesized that raising awareness to the psychological bias of naïve realism and its identification in oneself would provide a path to overcoming this barrier, thus increasing openness to the adversary's narrative. We conducted three experimental studies in the context of the Israeli-Palestinian conflict. Studies 1 and 2, conducted among Jewish Israelis and Palestinian Israelis, respectively, revealed that participants with hawkish political ideology reported greater openness to the adversary's narrative when they were made aware of naïve realism bias. Study 3 revealed that hawkish participants at the baseline adhered to the ingroup narrative and resisted the adversary's narrative more than dovish participants. They were also more able to identify the bias in themselves upon learning about it. This identification may explain why the manipulation led to bias correction only among hawkish participants.}, } @article {pmid25244421, year = {2014}, author = {Reddy, LA and Mikesh, L and Moskulak, C and Harvey, J and Sherman, N and Zigrino, P and Mauch, C and Fox, JW}, title = {Host response to human breast Invasive Ductal Carcinoma (IDC) as observed by changes in the stromal proteome.}, journal = {Journal of proteome research}, volume = {13}, number = {11}, pages = {4739-4751}, doi = {10.1021/pr500620x}, pmid = {25244421}, issn = {1535-3907}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Chromatography, Liquid ; Computational Biology ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunohistochemistry ; Mass Spectrometry ; Proteome/*metabolism ; Proteomics/methods ; Stromal Cells/*metabolism ; Tumor Microenvironment/*physiology ; }, abstract = {Following initial transformation, tumorigenesis, growth, invasion, and metastasis involves a complex interaction between the transformed tissue and the host, particularly in the microenvironment adjacent to the developing tumor. The tumor microenvironment itself is a unique outcome of the host reacting to the tumor and perhaps the tumor reacting to the host and in turn the tumor altering the host's response to give rise to an environment that ultimately promotes tumor progression. The tumor-adjacent stromal, sometimes referred to as "reactive stromal" or the desmoplastic stroma, has received some investigative studies, but it is incomplete, and likely different tumors promote a varied response and hence different reactive stroma. In this study, we have investigated the proteomics of the host response, both in vitro and in vivo, to breast epithelial cancer, in the former using tissue culture and in the latter laser microdissection of stromal tissue both adjacent and distal to breast invasive ductal cancer (IDC). From proteomic analysis of in vitro tissue culture studies, we observed that the stroma produced is related to the invasiveness of the stimulating breast cancer cell lines but different from that observed from the stromal proteome of archival tissue. In vivo we have identified several potential markers of a reactive stroma. Furthermore, we observed that the proteome of tumor-adjacent stroma differs from that of tumor-distal stroma. The proteomic description of human breast IDC stroma may serve to enhance our understanding of the role of stroma in the progression of cancer and may suggest potential mechanisms of therapeutic interdiction.}, } @article {pmid25232431, year = {2014}, author = {Oktay, M and Oktay, NA and Besir, FH and Buyukkaya, R and Erdem, H and Onal, B and Ozaydın, I and Yazıcı, B}, title = {Relation between radiographic BI-RADS scores and triple negativity in patients with ductal carcinomas.}, journal = {International journal of clinical and experimental medicine}, volume = {7}, number = {8}, pages = {2334-2338}, pmid = {25232431}, issn = {1940-5901}, abstract = {UNLABELLED: The aim of this study was to investigate association of radiographic (BI-RADS 4 and 5) results and prognostic factors of invasive ductal carcinomas with their histopathological subtypes. A total of 103 patients histopathologically diagnosed with invasive ductal carcinoma of breast with in last five years period were enrolled. Of them, 69 patients who had radiological reports in were included from registry of Radiology Department; Duzce University Training and Research Hospital archives. BI-RADS scores (4 and 5) of radiological reports and subtypes of ductal carcinoma were compared. Of 69 cases, 12 of 22 cases with BIRADS 4 score were Triple negative (TN) while 5 of 47 cases with BIRADS 5 score were TN (p = 0.001). The patients with TN tumors were found to have lower average age, higher grade, higher Ki67 proliferative index and fewer lymph node metastasis than those with non-TN ductal carcinomas (p = 0.048; 0.019; 0.02; 0.048 respectively).

CONCLUSIONS: Patients who had radiological BIRADS 4 score were significantly more frequent TN type carcinoma than BI-RADS 5. It is important to pay attention to this issue when clinicians evaluate patients with BI-RADS 4 score breast lesions.}, } @article {pmid25231588, year = {2014}, author = {Gabanti, E and Bruno, F and Fornara, C and Bernuzzi, S and Lilleri, D and Gerna, G}, title = {Polyfunctional analysis of human cytomegalovirus (HCMV)-specific CD4(+) and CD8 (+) memory T-cells in HCMV-seropositive healthy subjects following different stimuli.}, journal = {Journal of clinical immunology}, volume = {34}, number = {8}, pages = {999-1008}, pmid = {25231588}, issn = {1573-2592}, mesh = {Adult ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*chemistry ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*immunology ; Flow Cytometry ; Healthy Volunteers ; Humans ; Immunization ; *Immunologic Memory ; Middle Aged ; }, abstract = {PURPOSE: Following primary human cytomegalovirus (HCMV) infection, both humoral and T-cell-mediated immune responses develop in immunocompetent subjects. However, while antibodies may be measured by different methodologies, the T-cell-mediated response remains to be analyzed in its polyfunctional aspects, in view of defining (following different stimuli) the optimal assay to monitor the HCMV-specific T-cell response in HCMV-seropositive subjects.

METHODS: In a group of 30 HCMV-seropositive adults, T-cell response revealed by the HCMV-infected dendritic cell (iDC) stimulus was compared with those given by the HCMV-infected cell lysate (iCL), and by a 34-peptide pool (PP).

RESULTS: All HCMV-seropositive subjects showed presence of both HCMV-specific CD4(+) and CD8(+) T-cells in peripheral blood following iDC stimulation. One subject did not respond to PP. As compared to iDC, the number of HCMV-specific stimulated T-cells/μl blood was slightly lower for iCL (P = 0.195) and significantly lower for PP (P = 0.001). Polyfunctional analysis of the T-cell response indicated that the lower number of CD4(+) T-cells stimulated by iCL was due to the bifunctional (IFN-γ(+) TNF-α(+)) and CD40L-negative T-cell reduction, while the reduction in specific PP-stimulated CD8(+) T-cells was attributable to the reduction in tri-(IFN-γ(+) TNF-α(+) IL2(+)), bi-(IFN-γ(+) TNF-α(+)) and mono-(IFN-γ(+)) functional T-cells. In addition, 15/30 (50 %) subjects showed a CD4(+) cross-response to PP, and 11/30 (37 %) a CD8(+) cross-response to iCL.

CONCLUSIONS: HCMV-specific stimulus given by iDC is not significantly different from that of iCL on CD4(+) and is significantly superior to that of PP on CD8+ T-cells. However, iCL may contribute significantly to CD8(+), and PP to CD4(+) T-cell stimulation.}, } @article {pmid25230850, year = {2014}, author = {Zheng, L and Zhou, B and Meng, X and Zhu, W and Zuo, A and Wang, X and Jiang, R and Yu, S}, title = {A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer.}, journal = {International journal of oncology}, volume = {45}, number = {6}, pages = {2241-2249}, pmid = {25230850}, issn = {1791-2423}, mesh = {Animals ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*genetics/pathology ; Cyclin D1/biosynthesis/genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Proto-Oncogene Proteins c-myc/biosynthesis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.}, } @article {pmid25230018, year = {2014}, author = {Yoda, T and McNamara, KM and Miki, Y and Takagi, M and Rai, Y and Ohi, Y and Sagara, Y and Tamaki, K and Hirakawa, H and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.}, journal = {Cancer science}, volume = {105}, number = {11}, pages = {1503-1509}, pmid = {25230018}, issn = {1349-7006}, mesh = {3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Androgens/*metabolism ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Lobular/genetics/*metabolism/*pathology ; Estradiol Dehydrogenases/genetics/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Tumor Burden ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (P = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen-producing enzymes could play pivotal protective roles in AR-enriched ILC cases.}, } @article {pmid25228889, year = {2014}, author = {Friedman, D and Pizarro, R and Or-Berkers, K and Neyret, S and Pan, X and Slater, M}, title = {A method for generating an illusion of backwards time travel using immersive virtual reality-an exploratory study.}, journal = {Frontiers in psychology}, volume = {5}, number = {}, pages = {943}, pmid = {25228889}, issn = {1664-1078}, support = {227985/ERC_/European Research Council/International ; }, abstract = {We introduce a new method, based on immersive virtual reality (IVR), to give people the illusion of having traveled backwards through time to relive a sequence of events in which they can intervene and change history. The participant had played an important part in events with a tragic outcome-deaths of strangers-by having to choose between saving 5 people or 1. We consider whether the ability to go back through time, and intervene, to possibly avoid all deaths, has an impact on how the participant views such moral dilemmas, and also whether this experience leads to a re-evaluation of past unfortunate events in their own lives. We carried out an exploratory study where in the "Time Travel" condition 16 participants relived these events three times, seeing incarnations of their past selves carrying out the actions that they had previously carried out. In a "Repetition" condition another 16 participants replayed the same situation three times, without any notion of time travel. Our results suggest that those in the Time Travel condition did achieve an illusion of "time travel" provided that they also experienced an illusion of presence in the virtual environment, body ownership, and agency over the virtual body that substituted their own. Time travel produced an increase in guilt feelings about the events that had occurred, and an increase in support of utilitarian behavior as the solution to the moral dilemma. Time travel also produced an increase in implicit morality as judged by an implicit association test. The time travel illusion was associated with a reduction of regret associated with bad decisions in their own lives. The results show that when participants have a third action that they can take to solve the moral dilemma (that does not immediately involve choosing between the 1 and the 5) then they tend to take this option, even though it is useless in solving the dilemma, and actually results in the deaths of a greater number.}, } @article {pmid25228385, year = {2014}, author = {Tan, X and Peng, J and Fu, Y and An, S and Rezaei, K and Tabbara, S and Teal, CB and Man, YG and Brem, RF and Fu, SW}, title = {miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {5}, pages = {435}, pmid = {25228385}, issn = {1465-542X}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; 1R21 CA159103-01/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*pharmacology ; BRCA1 Protein/*genetics/metabolism ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/*pharmacology ; DNA Repair ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*physiology ; Neoplasm Invasiveness ; RNA Interference ; Triple Negative Breast Neoplasms/drug therapy/*genetics/metabolism/pathology ; Ultraviolet Rays ; }, abstract = {INTRODUCTION: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.

METHODS: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays.

RESULTS: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression.

CONCLUSIONS: Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1 deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.}, } @article {pmid25227964, year = {2014}, author = {Kryh, CG and Pietersen, CA and Rahr, HB and Christensen, RD and Wamberg, P and Lautrup, MD}, title = {Re-resection rates and risk characteristics following breast conserving surgery for breast cancer and carcinoma in situ: A single-centre study of 1575 consecutive cases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {6}, pages = {784-789}, doi = {10.1016/j.breast.2014.08.011}, pmid = {25227964}, issn = {1532-3080}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Cohort Studies ; Denmark ; Female ; Humans ; *Mastectomy, Segmental ; Neoadjuvant Therapy ; Reoperation ; Risk Factors ; }, abstract = {OBJECTIVES: To examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy.

RESULTS: 1703 breast conserving surgeries were performed: 1575 primary breast conserving surgeries (BCS), and 128 diagnostic excisions (DE). 176 BCS (11.2% [9.6; 12.7]) and 100 DE had inadequate margins indicating re-resection. The overall re-resection rate was 16.2% [14.5; 18.0]. 10.3% of invasive carcinoma BCS patients, and 28.6% CIS patients underwent re-resection (relative risk (RR) 2.8 [1.9; 4.1]). Invasive lobular carcinoma (ilc) had an RR of re-resection of 2.5 [1.7; 3.8], compared with invasive ductal carcinoma (idc).

CONCLUSION: Overall 11.2% of the BCS patients needed a re-resection. For isolated CIS (28.6%), RR of re-resection was almost three times as high compared to invasive carcinoma (10.3%). Ilc had an RR of re-resection of 2.5 compared to idc. Palpability and neoadjuvant chemotherapy did not significantly influence the risk of re-resection.}, } @article {pmid25227232, year = {2016}, author = {Eren, OO and Ordu, C and Selcuk, NA and Akosman, C and Ozturk, MA and Özkan, F and Gokce, Ö and Oyan, B}, title = {Bilateral synchronous adrenal metastasis of invasive ductal carcinoma treated with multimodality therapy including adrenalectomy and oophorectomy.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {22}, number = {1}, pages = {157-160}, doi = {10.1177/1078155214551314}, pmid = {25227232}, issn = {1477-092X}, mesh = {Adrenal Gland Neoplasms/*pathology/surgery/*therapy ; Adrenalectomy/methods ; Biopsy/methods ; Breast Neoplasms/*pathology/surgery/*therapy ; Carcinoma, Ductal, Breast/*pathology/surgery/*therapy ; Female ; Humans ; Ovariectomy/methods ; }, abstract = {A 38-year-old woman presented with a mass in the left breast. Biopsy of the lesion revealed invasive ductal carcinoma. Bilateral adrenal metastasis was detected in whole body positron emission tomography scanning. Needle biopsy of the left adrenal lesion proved infiltration of malignant cells from breast carcinoma. After eight cycles of neoadjuvant (preoperative) chemotherapy, mastectomy, bilateral adrenalectomy, and bilateral oopherectomy were performed. No further hormonal treatment was recommended due to the resection of both adrenal glands and ovaries. The patient is still followed without any sign of progression. To our knowledge, this is the first case representing multimodality approach to breast cancer with bilateral synchronous adrenal metastasis. Patients with oligometastatic disease may benefit from aggressive treatment including local therapies.}, } @article {pmid25225893, year = {2014}, author = {Mamidi, S and Lee, RK and Goos, JR and McClean, PE}, title = {Genome-wide association studies identifies seven major regions responsible for iron deficiency chlorosis in soybean (Glycine max).}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e107469}, pmid = {25225893}, issn = {1932-6203}, mesh = {Alleles ; Chromosome Mapping ; Disease Resistance/genetics ; Epistasis, Genetic ; Genes, Plant ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Genotype ; *Iron Deficiencies ; Linkage Disequilibrium ; Molecular Sequence Annotation ; Phenotype ; Plant Diseases/*genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Soybeans/*genetics/*metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) is a yield limiting problem in soybean (Glycine max (L.) Merr) production regions with calcareous soils. Genome-wide association study (GWAS) was performed using a high density SNP map to discover significant markers, QTL and candidate genes associated with IDC trait variation. A stepwise regression model included eight markers after considering LD between markers, and identified seven major effect QTL on seven chromosomes. Twelve candidate genes known to be associated with iron metabolism mapped near these QTL supporting the polygenic nature of IDC. A non-synonymous substitution with the highest significance in a major QTL region suggests soybean orthologs of FRE1 on Gm03 is a major gene responsible for trait variation. NAS3, a gene that encodes the enzyme nicotianamine synthase which synthesizes the iron chelator nicotianamine also maps to the same QTL region. Disease resistant genes also map to the major QTL, supporting the hypothesis that pathogens compete with the plant for Fe and increase iron deficiency. The markers and the allelic combinations identified here can be further used for marker assisted selection.}, } @article {pmid25224685, year = {2015}, author = {Ganoth, A and Merimi, KC and Peer, D}, title = {Overcoming multidrug resistance with nanomedicines.}, journal = {Expert opinion on drug delivery}, volume = {12}, number = {2}, pages = {223-238}, doi = {10.1517/17425247.2015.960920}, pmid = {25224685}, issn = {1744-7593}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; *Drug Delivery Systems ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanomedicine ; Nanoparticles ; Neoplasms/*drug therapy/pathology ; }, abstract = {INTRODUCTION: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.

AREAS COVERED: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.

EXPERT OPINION: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.}, } @article {pmid25224155, year = {2014}, author = {Li, J and Zhang, Y and Zhang, W and Gao, Y and Jia, S and Guo, J}, title = {Contrast enhanced computed tomography is indicative for angiogenesis pattern and display prognostic significance in breast cancer.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {672}, pmid = {25224155}, issn = {1471-2407}, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*diagnostic imaging/mortality/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; Humans ; Immunohistochemistry ; Microvessels/pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Neovascularization, Pathologic/*diagnostic imaging ; Prognosis ; Risk Factors ; Survival Analysis ; *Tomography, X-Ray Computed/methods ; }, abstract = {BACKGROUND: The Prognostic value of microvessel density in cancer remains unclear. Recent studies have suggested that the uneven distribution of microvessels in tumours caused the variation in sample selection which led to different prognostic outcome. The enhancement pattern of Contrast-enhanced computed tomography (CECT) is determined in part by the microvessel distribution in solid tumors. Therefore, survival analysis of tumors grouping by the enhancement pattern and the pattern of microvessel distribution is important.

METHODS: Survival analysis grouped by the tumor enhancement pattern and the microvessel distribution was carried out in 255 patients with invasive ductal carcinoma.

RESULTS: There were significant differences in overall survival (OS) and disease-free survival (DFS) among the homogeneous, heterogeneous and peripheral enhancement groups. There were significant differences between OS and DFS groups with uniform and uneven distributions of microvessels.

CONCLUSIONS: The distribution of microvessels in a tumor is a potential prognostic indicator in patients with breast cancer, and can be assessed by CECT prior the operation.}, } @article {pmid25222262, year = {2014}, author = {Cutright, KM and Erdem, T and Fitzsimons, GJ and Shachar, R}, title = {Finding brands and losing your religion?.}, journal = {Journal of experimental psychology. General}, volume = {143}, number = {6}, pages = {2209-2222}, doi = {10.1037/a0037876}, pmid = {25222262}, issn = {1939-2222}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Religion ; *Self Concept ; *Social Identification ; Young Adult ; }, abstract = {Religion is a powerful force in many people's lives, impacting decisions about life, death, and everything in between. It may be difficult, then, to imagine that something as seemingly innocuous as the usage of brand name products might influence individuals' commitment to religion. However, we demonstrate across 6 studies that when brands are a highly salient tool for self-expression, individuals are less likely to report and demonstrate strong religious commitment. We suggest that a desire to maintain consistency among self-identities is one important driver of this relationship and find that the effect is mitigated when the perceived distance between brands and religious values is minimized.}, } @article {pmid25216573, year = {2014}, author = {Hapdey, S and Edet-Sanson, A and Gouel, P and Martin, B and Modzelewski, R and Baron, M and Berghian, A and Forestier-Lebreton, F and Georgescu, D and Picquenot, JM and Gardin, I and Dubray, B and Vera, P}, title = {Delineation of small mobile tumours with FDG-PET/CT in comparison to pathology in breast cancer patients.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {112}, number = {3}, pages = {407-412}, doi = {10.1016/j.radonc.2014.08.005}, pmid = {25216573}, issn = {1879-0887}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Mammography/methods ; Middle Aged ; Multimodal Imaging/methods ; Positron-Emission Tomography/*methods ; Prospective Studies ; *Radiopharmaceuticals ; Tomography, X-Ray Computed/*methods ; Tumor Burden ; }, abstract = {PURPOSE: Various segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours.

METHODS: Thirty women with T2-T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions.

RESULTS: The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5
CONCLUSIONS: When compared with pathology, small lesions (diameter <50mm) with limited respiratory displacement (i.e., breast or apical lung lesions) are best delineated on FDG-PET/CT using a 50% SUVmax threshold. The acquisition position and respiratory gating did not modify the delineated volumes.}, } @article {pmid25216158, year = {2014}, author = {Hermawati, S and Lawson, G and Sutarto, AP}, title = {Mapping ergonomics application to improve SMEs working condition in industrially developing countries: a critical review.}, journal = {Ergonomics}, volume = {57}, number = {12}, pages = {1771-1794}, doi = {10.1080/00140139.2014.953213}, pmid = {25216158}, issn = {1366-5847}, mesh = {*Developing Countries ; Ergonomics/*methods/standards/statistics & numerical data ; Humans ; Indonesia ; *Occupational Health/statistics & numerical data ; Quality Improvement ; Small Business/*methods/standards/statistics & numerical data ; }, abstract = {In industrially developing countries (IDC), small and medium enterprises (SMEs) account for the highest proprotion of employment. Unfortunately, the working conditions in SMEs are often very poor and expose employees to a potentially wide range of health and safety risks. This paper presents a comprehensive review of 161 articles related to ergonomics application in SMEs, using Indonesia as a case study. The aim of this paper is to investigate the extent of ergonomics application and identify areas that can be improved to promote effective ergonomics for SMEs in IDC. The most urgent issue found is the need for adopting participatory approach in contrast to the commonly implemented top-down approach. Some good practices in ergonomics application were also revealed from the review, e.g. a multidisciplinary approach, unsophisticated and low-cost solutions, and recognising the importance of productivity. The review also found that more work is still required to achieve appropriate cross-cultural adaptation of ergonomics application.}, } @article {pmid25209856, year = {2014}, author = {Kondo, Y and Kikuchi, T and Esteban, JC and Kumaki, N and Ogura, G and Inomoto, C and Hirabayashi, K and Kajiwara, H and Sakai, A and Sugimoto, R and Otsuru, M and Okami, K and Tsukinoki, K and Nakamura, N}, title = {Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma.}, journal = {Pathology international}, volume = {64}, number = {9}, pages = {453-459}, doi = {10.1111/pin.12195}, pmid = {25209856}, issn = {1440-1827}, mesh = {Adenocarcinoma/genetics/*metabolism/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Child ; Child, Preschool ; Gene Amplification ; *Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization/methods ; Male ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Salivary Gland Neoplasms/genetics/*metabolism/pathology ; Young Adult ; }, abstract = {Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.}, } @article {pmid25207183, year = {2014}, author = {Yıldız, B and Fidan, E and Ozdemir, F and Sezen, O and Kavgacı, H and Aydın, F}, title = {Clinicopathological Characteristics of Triple-negative Breast Cancers in the Northeast Region of Turkey.}, journal = {Balkan medical journal}, volume = {31}, number = {2}, pages = {126-131}, pmid = {25207183}, issn = {2146-3123}, abstract = {BACKGROUND: Triple-negative (TN) breast cancer is a subtype of breast cancer characterised by a loss of estrogen receptor (ER), progesterone receptor (PR) expression, and the absence of human epidermal growth factor (HER2) overexpression.

AIMS: To identify the relationships between clinicopathological characteristics of TN breast cancers in the northeast region of Turkey and disease free survival (DFS) and overall survival (OS).

STUDY DESIGN: Retrospective clinical study.

METHODS: Seven hundred and eighty non-metastatic breast cancer patients were enrolled in this study. The relationships between TN breast cancer and other breast cancers with respect to clinicopathological characteristics, as well as DFS and OS, were studied.

RESULTS: The triple-negative phenotype was detected in 204 patients (27.1%). Patients with triple-negative breast cancer had more grade 2-3 tumours compared to those with other types of breast cancer (92.5% versus 84.3%, p=0.004). Invasive ductal carcinoma histology, on the other hand, was less prevalent in patients with TN breast cancer (77% versus 84.5%, p=0.016). No significant differences were identified between the groups in other clinicopathological variables. Relapse and mortality rates were higher in the TN group during the follow-up of both groups [57 (27.9%) versus 89 (16.2%), p<0.001 for relapse; 27 (13.2%) versus 37 (6.8%), p=0.005 for mortality]. The univariate analysis demonstrated shorter DFS and OS for patients with TN breast cancer compared to those with other types of breast cancer. In the multivariate analysis, patients with TN breast cancer were 2.21 times more likely to develop relapse, while the likelihood of death increased 3.21-fold (p<0.001 and p<0.001).

CONCLUSION: Triple-negative breast cancers demonstrate a more aggressive clinical course compared to other breast cancers. More effective strategies should be developed for the treatment of this subgroup of breast cancer.}, } @article {pmid25205656, year = {2014}, author = {List, T and Casi, G and Neri, D}, title = {A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity.}, journal = {Molecular cancer therapeutics}, volume = {13}, number = {11}, pages = {2641-2652}, doi = {10.1158/1535-7163.MCT-14-0599}, pmid = {25205656}, issn = {1538-8514}, mesh = {Animals ; Antibodies/chemistry/immunology/*pharmacology ; CHO Cells ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Cytokines/chemistry/immunology/*pharmacology ; Disease Models, Animal ; Female ; Humans ; Immunotoxins/*chemistry/immunology/*pharmacology ; Male ; Mice ; Neoplasms/*drug therapy/immunology ; }, abstract = {The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models.}, } @article {pmid25204617, year = {2014}, author = {Cozzolino, I and Ciancia, G and Limite, G and Di Micco, R and Varone, V and Cortese, A and Vatrella, A and Di Crescenzo, V and Zeppa, P}, title = {Neuroendocrine differentiation in breast carcinoma with osteoclast-like giant cells. Report of a case and review of the literature.}, journal = {International journal of surgery (London, England)}, volume = {12 Suppl 2}, number = {}, pages = {S8-S11}, doi = {10.1016/j.ijsu.2014.08.392}, pmid = {25204617}, issn = {1743-9159}, mesh = {Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biopsy, Fine-Needle ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Neuroendocrine/metabolism/*pathology ; Cell Differentiation ; Female ; Giant Cells/metabolism/*pathology ; Humans ; Osteoclasts/metabolism/*pathology ; Retrospective Studies ; }, abstract = {Osteoclast-like giant cells (OGCs) may occur in several types of breast carcinomas (BS). Neuroendocrine differentiation may be present in BS but, associated with OGCs, neuroendocrine differentiation has been rarely reported. A case of invasive ductal carcinoma with OGCs and neuroendocrine differentiation diagnosed by fine needle cytology (FNC) is described. A 72-year-old woman with a nodular lesion of the right breast underwent to fine-needle cytology (FNC) The smears showed a dissociated cell population of monomorphous, mononucleated atypical cells with interspersed multinucleated giant cells osteoclast-like. The mononuclear cell component showed plasmacytoid features and frequent vacuoles of secretion. Immunostaining (IHC) performed on cell block sections showed oestrogen receptor positivity in the mononucleated cells and OGCs positivity for LCA and CD68. Histologically the tumour showed cell nests or cords separated by thin fibrovascular septa. The neoplastic cells were monomorphic, with round-oval nuclei, granular chromatin and evident nucleoli. The cytoplasm was indistinct and eosinophilic, finely granular, often containing eosinophilic globules that were positive at the PAS and mucicarmine stainings. Numerous non-neoplastic OGCs were also detected in the interstitial septa. The ICH showed positivity of the tumoral cells for E-Cadherin, oestrogen and progesterone receptors and c-ErbB2 negativity. Mitotic index was inconspicuous with a low Ki67 positivity rate (<10%). OCGs were CD68 and LCA positive. IHC also showed strong positivity for the chromogranin and synaptophysin. A diagnosis of invasive ductal BC with OGCs and neuroendocrine differentiation was performed. The expression of chromogranin and synaptophysin was then retrospectively assessed on CB sections too. The identification of OGCs component on breast FNA samples is not difficult, depending on a good sampling only. On contrary, the neuroendocrine differentiation still represents still a challenge in breast FNC.}, } @article {pmid25202063, year = {2014}, author = {Pula, B and Olbromski, M and Owczarek, T and Ambicka, A and Witkiewicz, W and Ugorski, M and Rys, J and Zabel, M and Dziegiel, P and Podhorska-Okolow, M}, title = {Nogo-B receptor expression correlates negatively with malignancy grade and ki-67 antigen expression in invasive ductal breast carcinoma.}, journal = {Anticancer research}, volume = {34}, number = {9}, pages = {4819-4828}, pmid = {25202063}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/mortality/*pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Female ; Fibroblasts/metabolism ; Follow-Up Studies ; Gene Expression ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Receptors, Cell Surface/genetics/*metabolism ; }, abstract = {BACKGROUND: Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed.

MATERIALS AND METHODS: We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness.

RESULTS: NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=-0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129).

CONCLUSION: NgBR may be involved in IDC development, however, its role in its progression requires further research.}, } @article {pmid25192983, year = {2015}, author = {Chu, J and Wang, T and Pei, S and Yin, Z}, title = {Surgical treatment for idiopathic intervertebral disc calcification in a child: case report and review of the literature.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {31}, number = {1}, pages = {123-127}, pmid = {25192983}, issn = {1433-0350}, mesh = {Adolescent ; Calcinosis/*complications/*surgery ; Decompression, Surgical/*methods ; Humans ; Intervertebral Disc/*surgery ; Intervertebral Disc Degeneration/*complications/*surgery ; Male ; }, abstract = {PURPOSE: Intervertebral disc calcification (IDC) is rare in children. Conservative treatment has been recommended for the majority of cases. We describe surgical treatment of a case of IDC with progressive neurological impairment and review the literature relevant to this rare entity and its management.

METHODS: A 16-year-old boy presented with sudden onset of severe neck pain, radiating into his left shoulder. Three months later, he developed neurological symptoms and signs with a progressive motor and sensory loss of his left upper limb.

RESULTS: Anterior cervical corpectomy with fusion and instrumentation was performed. Neurologic deficits completely resolved within 1 week. After 1-year follow-up, radiological images showed solid fusion and no further compression.

CONCLUSION: Surgical decompression should be recommended for cases with acutely progressive and severe neurological impairments in IDC and a good result can be obtained. When surgery is needed, anterior decompression is usually used in cervical lesion, while in thoracic and lumbar area, posterior approach is suggested.}, } @article {pmid25192706, year = {2014}, author = {Chen, L and Malone, KE and Li, CI}, title = {Bra wearing not associated with breast cancer risk: a population-based case-control study.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {23}, number = {10}, pages = {2181-2185}, pmid = {25192706}, issn = {1538-7755}, support = {R01 CA085913/CA/NCI NIH HHS/United States ; R01CA 85913/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*epidemiology ; Carcinoma/*epidemiology ; Case-Control Studies ; Clothing/*adverse effects ; Female ; Humans ; Middle Aged ; Risk Factors ; United States/epidemiology ; }, abstract = {Despite the widespread use of bras among U.S. women and concerns in the lay media that bra wearing may increase breast cancer risk, there is a scarcity of credible scientific studies addressing this issue. The goal of the study was to evaluate the relationship between various bra-wearing habits and breast cancer risk among postmenopausal women. We conducted a population-based case-control study of breast cancer in the Seattle-Puget Sound metropolitan area that compared 454 invasive ductal carcinoma (IDC) cases and 590 invasive lobular carcinoma (ILC) cases diagnosed between 2000 and 2004 with 469 control women between 55 to 74 years of age. Information on bra-wearing habits and other breast cancer risk factors was collected from study participants through in-person interviews. Multivariate adjusted odds ratios (OR) and their associated 95% confidence intervals (CI) were estimated using polytomous logistic regression. No aspect of bra wearing, including bra cup size, recency, average number of hours/day worn, wearing a bra with an underwire, or age first began regularly wearing a bra, was associated with risks of either IDC or ILC. Our results did not support an association between bra wearing and increased breast cancer risk among postmenopausal women.}, } @article {pmid25188383, year = {2014}, author = {Liu, Y and Huang, X and Bi, R and Yang, W and Shao, Z}, title = {Similar prognoses for invasive micropapillary breast carcinoma and pure invasive ductal carcinoma: a retrospectively matched cohort study in China.}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e106564}, pmid = {25188383}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; China ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive micropapillary breast carcinoma (IMPC) is a rare pathological finding. Few studies have compared IMPC with invasive ductal breast carcinoma (IDC) according to matched nodal status and age. To better illustrate the difference between IMPC and IDC prognoses, we conducted this cohort study.

METHODS: 51 mixed or pure IMPC patients and 102 pure IDC patients were matched for nodal status and age. Clinical and biological features as well as disease-free survival (DFS) were compared between groups.

RESULTS: More than one-half of IMPC consisted of mostly or exclusively IMPC component (meaning greater than 75%) and these tumors significantly correlated with a higher histologic grade (P = 0.016) and LVI positivity (P = 0.036) compared with mixed IMPC. IMPC displayed a significantly higher rate of estrogen receptor (ER) positivity and lymphovascular invasion (LVI) compared to matched IDC. Women diagnosed with IMPC had a slight, but not significant, reduced frequency for recurrence and metastasis compared to women with IDC (15.7% vs. 21.6%, P = 0.518). In the subgroup analysis, IMPC patients demonstrated significantly reduced survival (P = 0.018) compared to IDC patients in the T1N2-3 subpopulation, whereas IDC patients demonstrated significantly increased recurrence and metastasis (P = 0.024) compared to IMPC patients in the T2N2-3 subgroup. No difference was observed in patients with 3 or less positive lymph nodes (LNs).

CONCLUSION: Although no difference in DFS was observed between IMPC and LN-matched IDC patients, IMPC patients demonstrated a significantly poorer outcome compared to IDC patients with smaller tumors and 4 or more positive LNs. The opposite results were observed in larger tumors and patients with 4 or more positive LNs. Therefore, we might advise more proactive treatment for IMPC patients with a smaller tumor size and extensive LN involvement. Furthermore, correlative IMPC studies should focus on this subset of patients to elucidate the genetic and/or biologic differences that contribute to metastatic potential.}, } @article {pmid25179880, year = {2015}, author = {Yıldız, A and Yüksel, M and Oylumlu, M and Polat, N and Akıl, MA and Acet, H}, title = {The association between the neutrophil/lymphocyte ratio and functional capacity in patients with idiopathic dilated cardiomyopathy.}, journal = {Anatolian journal of cardiology}, volume = {15}, number = {1}, pages = {13-17}, pmid = {25179880}, issn = {2149-2271}, mesh = {Cardiomyopathy, Dilated/blood/diagnostic imaging/*physiopathology ; Echocardiography ; Exercise Test ; Female ; Humans ; Lymphocytes/*physiology ; Male ; Middle Aged ; Neutrophils/*physiology ; Predictive Value of Tests ; Severity of Illness Index ; }, abstract = {OBJECTIVE: The neutrophil/lymphocyte ratio (NLR) is an inexpensive, readily available and reliable inflammatory marker, which has a predictor value in different cardiovascular disorders. Functional capacity is one of the most important prognostic factors in patients with heart failure, which is usually stated as metabolic equivalents (MET). The goal of the study was to investigate the relationship between the NLR and functional capacity (FC) in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS: Treadmill test according to modified-Bruce protocol was performed in 37 patients with IDC (mean age 46.7±11.7 years, 81.1% male) to assess their functional capacity. Baseline clinical and echocardiographic variables were obtained. Hematological and biochemical parameters were measured using standard techniques.

RESULTS: The patients were divided into low (<5 MET, n=18) and high (>5 MET, n=19) FC groups according to their functional status in the exercise test. The 2 groups were similar regarding age, gender and the presence of hypertension and diabetes mellitus. There was no significant difference between groups regarding echocardiographic parameters such as left ventricular ejection fraction and diameters. However, the NLR was significantly higher in low FC group compared to high FC group (3.62±2.24 vs. 2.24±0.67, p=0.002; respectively). There were significant negative correlations between the NLR, MET and left ventricular ejection fraction (r=-0.405, p=0.013 and r=-0.028, p=0.028; respectively). Diastolic dysfunction was present in all the patients with low functional capacity. A cut-off point of 2.26 for the NLR had 83% sensitivity and 69% specificity in predicting poor FC. After multivariate analysis, only the NLR remained significant predictor of poor functional status.

CONCLUSION: We detected a significant association between the NLR and low FC, both of which has predictive and prognostic value in patients with heart failure. Functional capacity may depend on diastolic function rather than left ventricular ejection fraction in patients with IDC.}, } @article {pmid25176936, year = {2014}, author = {De Castro-Orós, I and Cenarro, A and Tejedor, MT and Baila-Rueda, L and Mateo-Gallego, R and Lamiquiz-Moneo, I and Pocoví, M and Civeira, F}, title = {Common genetic variants contribute to primary hypertriglyceridemia without differences between familial combined hyperlipidemia and isolated hypertriglyceridemia.}, journal = {Circulation. Cardiovascular genetics}, volume = {7}, number = {6}, pages = {814-821}, doi = {10.1161/CIRCGENETICS.114.000522}, pmid = {25176936}, issn = {1942-3268}, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Adult ; Age Factors ; Alleles ; Apolipoprotein A-V ; Apolipoproteins A/genetics ; Blood Glucose/analysis ; Body Mass Index ; Female ; Gene Frequency ; *Genetic Variation ; Genotype ; Humans ; Hyperlipidemia, Familial Combined/*genetics/pathology ; Hypertriglyceridemia/*genetics/pathology ; Lipoprotein Lipase/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sex Factors ; Triglycerides/blood ; }, abstract = {BACKGROUND: The majority of hypertriglyceridemias are diagnosed as familial combined hyperlipidemia (FCHL) and primary isolated hypertriglyceridemias. The contribution of common genetic variants in primary hypertriglyceridemias and the genetic difference between FCHL and isolated hypertriglyceridemias have not been thoroughly examined.

METHODS AND RESULTS: This study involved 580 patients with hypertriglyceridemias and 403 controls. Of the 37 single nucleotide polymorphisms examined, 12 located in 10 genes showed allelic and genotype frequency differences between hypertriglyceridemias and controls. The minor alleles of APOE, APOA5, GALNTN2, and GCKR variants were positively correlated with plasma triglycerides, whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated. Body mass index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in GCKR explained 36% of the variability in plasma triglycerides, 7.3% of which was attributable to the genetic variables. LPL, GCKR, and APOA5 polymorphisms fit dominant, recessive, and additive inheritance models, respectively. Variants more frequently identified in isolated hypertriglyceridemias were rs7412 in APOE and rs1800795 in IL6; rs2808607 in CYP7A1 and rs3812316 and rs17145738 in MLXIPL were more frequent in FCHL. The other 32 single nucleotide polymorphisms presented similar frequencies between isolated hypertriglyceridemias and FCHL.

CONCLUSIONS: Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides levels in patients with primary hypertriglyceridemias. FCHL and isolated hypertriglyceridemias are probably trace to an accumulation of genetic variants predisposing to familial and sporadic hypertriglyceridemias or to hypertriglyceridemias and hypercholesterolemia in case of FCHL.}, } @article {pmid25174061, year = {2014}, author = {Zemanova, M and Rauova, K and Boljesikova, E and Machalekova, K and Krajcovicova, I and Lehotska, V and Mikulova, M and Svec, J}, title = {Analysis of radiation-induced angiosarcoma of the breast.}, journal = {Bratislavske lekarske listy}, volume = {115}, number = {5}, pages = {307-310}, doi = {10.4149/bll_2014_062}, pmid = {25174061}, issn = {0006-9248}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms/diagnosis/*radiotherapy/therapy ; Carcinoma, Ductal, Breast/*radiotherapy/therapy ; Combined Modality Therapy/methods ; Female ; Hemangiosarcoma/*diagnosis ; Humans ; Lymph Node Excision ; Magnetic Resonance Imaging ; Neoplasm Invasiveness ; Neoplasms, Radiation-Induced/*diagnosis ; }, abstract = {Breast angiosarcoma may occur de novo, or as a complication of radiation therapy, or chronic lymphedema secondary to axillary lymph node dissection for mammary carcinoma. Both primary and secondary angiosarcomas may present with bruise like skin discoloration, which may delay the diagnosis. Imaging findings are nonspecific. In case of high-grade tumours, MRI may be used effectively to determine lesion extent by showing rapid enhancement, nevertheless earliest possible diagnostics is crucial therefore any symptoms of angiosarcoma have to be carefully analysed. The case analysed here reports on results of 44-year old premenopausal woman who was treated for a T1N1M0 invasive ductal carcinoma. After a biopsy diagnosis of carcinoma, the patient underwent quadrantectomy with axillary lymph node dissection. She received partial 4 cycles of chemotherapy with adriamycin and cyclophosphamide, followed by radiation treatment. Thereafter, a standard postoperative radiotherapy was applied at our institution four months after chemotherapy (TD 46 Gy in 23 fractions followed by a 10 Gy electron boost to the tumour bed). Adjuvant chemotherapy was finished six months after operation, followed by tamoxifen. Follow up: no further complications were detected during regular check-ups. However, 12-years later, patient reported significant changes at breast region which was exposed to radiation during treatment of original tumour. In this article, we describe the clinical presentation, imaging and pathological findings of secondary angiosarcoma of the breast after radiotherapy (Fig. 2, Ref. 26).}, } @article {pmid25173099, year = {2015}, author = {Zhao, B and Xu, B and Hu, W and Song, C and Wang, F and Liu, Z and Ye, M and Zou, H and Miao, QR}, title = {Comprehensive proteome quantification reveals NgBR as a new regulator for epithelial-mesenchymal transition of breast tumor cells.}, journal = {Journal of proteomics}, volume = {112}, number = {}, pages = {38-52}, pmid = {25173099}, issn = {1876-7737}, support = {R01 HL108938/HL/NHLBI NIH HHS/United States ; R01HL108938/HL/NHLBI NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Cell Line, Tumor ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Neoplasm Proteins/genetics/*metabolism ; Proteome/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; }, abstract = {UNLABELLED: Nogo-B receptor (NgBR) is a type I receptor and specifically binds to ligand Nogo-B. Our previous work has shown that NgBR is highly expressed in human breast invasive ductal carcinoma. Here, comprehensive proteome quantification was performed to examine the alteration of protein expression profile in MDA-MB-231 breast tumor cells after knocking down NgBR using lentivirus-mediated shRNA approach. Among a total of 1771 proteins feasibly quantified, 994 proteins were quantified in two biological replicates with RSD <50%. There are 122 proteins significantly down-regulated in NgBR knockdown MDA-MB-231 breast tumor cells, such as vimentin and S100A4, well-known markers for mesenchymal cells, and CD44, a stemness indicator. The decrease of vimentin, S100A4 and CD44 protein expression levels was further confirmed by Western blot analysis. MDA-MB-231 cells are typical breast invasive ductal carcinoma cells showing mesenchymal phenotype. Cell morphology analysis demonstrates NgBR knockdown in MDA-MB-231 cells results in reversibility of epithelial-mesenchymal transition (EMT), which is one of the major mechanisms involved in breast cancer metastasis. Furthermore, we demonstrated that NgBR knockdown in MCF-7 cells significantly prevented the TGF-β-induced EMT process as determined by the morphology change, and staining of E-cadherin intercellular junction as well as the decreased expression of vimentin.

BIOLOGICAL SIGNIFICANCE: Our previous publication showed that NgBR is highly expressed in human breast invasive ductal carcinoma. However, the roles of NgBR and NgBR-mediated signaling pathway in breast tumor cells are still unclear. Here, we not only demonstrated that the quantitative proteomics analysis is a powerful tool to investigate the global biological function of NgBR, but also revealed that NgBR is involved in the transition of breast epithelial cells to mesenchymal stem cells, which is one of the major mechanisms involved in breast cancer metastasis. These findings provide new insights for understanding the roles of NgBR in regulating breast epithelial cell transform during the pathogenesis of breast cancer.}, } @article {pmid25171226, year = {2014}, author = {Samikkannu, T and Rao, KV and Ding, H and Agudelo, M and Raymond, AD and Yoo, C and Nair, MP}, title = {Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e106348}, pmid = {25171226}, issn = {1932-6203}, support = {R25 MH080663/MH/NIMH NIH HHS/United States ; DA 025576/DA/NIDA NIH HHS/United States ; R01 DA034547/DA/NIDA NIH HHS/United States ; DA034547/DA/NIDA NIH HHS/United States ; R37 DA025576/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Arachidonic Acid/*blood ; Cells, Cultured ; Cocaine/*adverse effects ; Cyclooxygenase 2/metabolism ; Dendritic Cells/*immunology ; Dinoprostone/blood ; Drug Users ; Female ; Gene Expression Regulation/drug effects ; HIV Infections/blood/*immunology/pathology ; Humans ; Intramolecular Oxidoreductases/blood ; Male ; Middle Aged ; Prostaglandin D2/*analogs & derivatives/blood ; Prostaglandin-E Synthases ; }, abstract = {Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.}, } @article {pmid25157354, year = {2014}, author = {Quarantelli, M and Palladino, O and Prinster, A and Schiavone, V and Carotenuto, B and Brunetti, A and Marsili, A and Casiello, M and Muscettola, G and Salvatore, M and de Bartolomeis, A}, title = {Patients with poor response to antipsychotics have a more severe pattern of frontal atrophy: a voxel-based morphometry study of treatment resistance in schizophrenia.}, journal = {BioMed research international}, volume = {2014}, number = {}, pages = {325052}, pmid = {25157354}, issn = {2314-6141}, mesh = {Adult ; Antipsychotic Agents/pharmacology/*therapeutic use ; Atrophy ; Demography ; Frontal Lobe/drug effects/*pathology ; Gray Matter/drug effects/pathology ; Humans ; Organ Size/drug effects ; Schizophrenia/*drug therapy/pathology ; Treatment Outcome ; }, abstract = {Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.}, } @article {pmid25154392, year = {2015}, author = {Risbridger, GP and Taylor, RA and Clouston, D and Sliwinski, A and Thorne, H and Hunter, S and Li, J and Mitchell, G and Murphy, D and Frydenberg, M and Pook, D and Pedersen, J and Toivanen, R and Wang, H and Papargiris, M and Lawrence, MG and Bolton, DM}, title = {Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis.}, journal = {European urology}, volume = {67}, number = {3}, pages = {496-503}, doi = {10.1016/j.eururo.2014.08.007}, pmid = {25154392}, issn = {1873-7560}, mesh = {Aged ; Animals ; BRCA2 Protein/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/*pathology/surgery ; Genetic Predisposition to Disease ; Heredity ; Heterografts ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; *Mutation ; Neoplasm Transplantation ; Pedigree ; Phenotype ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms/*genetics/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity associated with aggressive prostate cancer (PCa). PCa patients carrying a breast cancer 2, early onset (BRCA2) germline mutation exhibit highly aggressive tumours with poor prognosis.

OBJECTIVE: To investigate the presence and implications of IDC-P in men with a strong family history of PCa who either carry a BRCA2 pathogenic mutation or do not carry the mutation (BRCAX).

Patient-derived xenografts (PDXs) were generated from three germline BRCA2 mutation carriers and one BRCAX patient. Specimens were examined for histologic evidence of IDC-P. Whole-genome copy number analysis (WG-CNA) was performed on IDC-P from a primary and a matched PDX specimen.

The incidence of IDC-P and association with overall survival for BRCA2 and BRCAX patients were determined using Kaplan-Meier analysis.

RESULTS AND LIMITATIONS: PDXs from BRCA2 tumours showed increased incidence of IDC-P compared with sporadic PCa (p=0.015). WG-CNA confirmed that the genetic profile of IDC-P from a matched (primary and PDX) BRCA2 tumour was similar. The incidence of IDC-P was significantly increased in BRCA2 carriers (42%, n=33, p=0.004) but not in BRCAX patients (25.8%, n=62, p=0.102) when both groups were compared with sporadic cases (9%, n=32). BRCA2 carriers and BRCAX patients with IDC-P had significantly worse overall and PCa-specific survival compared with BRCA2 carriers and BRCAX patients without IDC-P (hazard ratio [HR]: 16.9, p=0.0064 and HR: 3.57, p=0.0086, respectively).

CONCLUSIONS: PDXs revealed IDC-P in patients with germline BRCA2 mutations or BRCAX classification, identifying aggressive tumours with poor survival even when the stage and grade of cancer at diagnosis were similar. Further studies of the prognostic significance of IDC-P in sporadic PCa are warranted.

PATIENT SUMMARY: Intraductal carcinoma of the prostate is common in patients with familial prostate cancer and is associated with poor outcomes. This finding affects genetic counselling and identifies patients in whom earlier multimodality treatment may be required.}, } @article {pmid25149281, year = {2014}, author = {Moran Lauter, AN and Peiffer, GA and Yin, T and Whitham, SA and Cook, D and Shoemaker, RC and Graham, MA}, title = {Identification of candidate genes involved in early iron deficiency chlorosis signaling in soybean (Glycine max) roots and leaves.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {702}, pmid = {25149281}, issn = {1471-2164}, mesh = {Binding Sites ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Homeostasis ; *Iron Deficiencies ; Multigene Family ; Plant Diseases/*genetics ; Plant Leaves/*genetics/metabolism ; Plant Roots/*genetics/metabolism ; Protein Binding ; *Signal Transduction ; Soybeans/*genetics/*metabolism ; Stress, Physiological ; Time Factors ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Iron is an essential micronutrient for all living things, required in plants for photosynthesis, respiration and metabolism. A lack of bioavailable iron in soil leads to iron deficiency chlorosis (IDC), causing a reduction in photosynthesis and interveinal yellowing of leaves. Soybeans (Glycine max (L.) Merr.) grown in high pH soils often suffer from IDC, resulting in substantial yield losses. Iron efficient soybean cultivars maintain photosynthesis and have higher yields under IDC-promoting conditions than inefficient cultivars.

RESULTS: To capture signaling between roots and leaves and identify genes acting early in the iron efficient cultivar Clark, we conducted a RNA-Seq study at one and six hours after replacing iron sufficient hydroponic media (100 μM iron(III) nitrate nonahydrate) with iron deficient media (50 μM iron(III) nitrate nonahydrate). At one hour of iron stress, few genes were differentially expressed in leaves but many were already changing expression in roots. By six hours, more genes were differentially expressed in the leaves, and a massive shift was observed in the direction of gene expression in both roots and leaves. Further, there was little overlap in differentially expressed genes identified in each tissue and time point.

CONCLUSIONS: Genes involved in hormone signaling, regulation of DNA replication and iron uptake utilization are key aspects of the early iron-efficiency response. We observed dynamic gene expression differences between roots and leaves, suggesting the involvement of many transcription factors in eliciting rapid changes in gene expression. In roots, genes involved iron uptake and development of Casparian strips were induced one hour after iron stress. In leaves, genes involved in DNA replication and sugar signaling responded to iron deficiency. The differentially expressed genes (DEGs) and signaling components identified here represent new targets for soybean improvement.}, } @article {pmid25148175, year = {2014}, author = {Trimboli, RM and Verardi, N and Cartia, F and Carbonaro, LA and Sardanelli, F}, title = {Breast cancer detection using double reading of unenhanced MRI including T1-weighted, T2-weighted STIR, and diffusion-weighted imaging: a proof of concept study.}, journal = {AJR. American journal of roentgenology}, volume = {203}, number = {3}, pages = {674-681}, doi = {10.2214/AJR.13.11816}, pmid = {25148175}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/*pathology ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Observer Variation ; Pilot Projects ; Reproducibility of Results ; Sensitivity and Specificity ; Single-Blind Method ; }, abstract = {OBJECTIVE: The purpose of this study was to investigate the diagnostic performance of unenhanced MRI in detecting breast cancer and to assess the impact of double reading.

MATERIALS AND METHODS: A total of 116 breasts of 67 women who were 36-89 years old were studied at 1.5 T using an unenhanced protocol including axial T1-weighted gradient-echo, T2-weighted STIR, and echo-planar diffusion-weighted imaging (DWI). Two blinded readers (R1 and R2) independently evaluated unenhanced images using the BIRADS scale. A combination of pathology and negative follow-up served as the reference standard. McNemar and kappa statistics were used.

RESULTS: Per-breast cancer prevalence was 37 of 116 (32%): 30 of 37 (81%) invasive ductal carcinoma, five of 37 (13%) ductal carcinoma in situ, and two of 37 (6%) invasive lobular carcinoma. Per-breast sensitivity of unenhanced MRI was 29 of 37 (78%) for R1, 28 of 37 (76%) for R2, and 29 of 37 (78%) for double reading. Specificity was 71 of 79 (90%) for both R1 and R2 and 69 of 79 (87%) for double reading. Double reading did not provide a significant increase in sensitivity. Interobserver agreement was almost perfect (Cohen κ = 0.873).

CONCLUSION: An unenhanced breast MRI protocol composed of T1-weighted gradient echo, T2-weighted STIR, and echo-planar DWI enabled breast cancer detection with sensitivity of 76-78% and specificity of 90% without a gain in sensitivity from double reading.}, } @article {pmid25147131, year = {2014}, author = {Bhattacharya-Ghosh, B and Bozkurt, S and Rutten, MC and van de Vosse, FN and Díaz-Zuccarini, V}, title = {An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system.}, journal = {Computers in biology and medicine}, volume = {53}, number = {}, pages = {141-153}, doi = {10.1016/j.compbiomed.2014.06.013}, pmid = {25147131}, issn = {1879-0534}, mesh = {Calcium/metabolism ; Cardiomyopathy, Dilated/*physiopathology ; Computational Biology ; *Computer Simulation ; Heart/physiology ; Humans ; *Models, Cardiovascular ; Muscle Proteins/metabolism ; *Myocardium/chemistry/cytology/metabolism ; Ventricular Pressure/physiology ; }, abstract = {Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.}, } @article {pmid25145777, year = {2014}, author = {Ahmed, Q and Avidan, AY and Ciechanover, A and Shechtman, D and Zajfman, D and Reichman, U and Kornberg, R and Hershko, A and Lavie, P}, title = {Israel-Gaza conflict.}, journal = {Lancet (London, England)}, volume = {384}, number = {9945}, pages = {e34-7}, doi = {10.1016/S0140-6736(14)61314-3}, pmid = {25145777}, issn = {1474-547X}, mesh = {Humans ; *Warfare ; }, } @article {pmid25141109, year = {2014}, author = {Sevim, Y and Kocaay, AF and Eker, T and Celasin, H and Karabork, A and Erden, E and Genc, V}, title = {Breast hamartoma: a clinicopathologic analysis of 27 cases and a literature review.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {69}, number = {8}, pages = {515-523}, pmid = {25141109}, issn = {1980-5322}, mesh = {Adult ; Angiomatosis/diagnostic imaging/*pathology ; Breast Diseases/diagnostic imaging/*pathology ; Female ; Hamartoma/diagnostic imaging/*pathology ; Humans ; Hyperplasia/diagnostic imaging/*pathology ; Mammography ; Middle Aged ; Turkey ; Ultrasonography ; Young Adult ; }, abstract = {OBJECTIVES: Breast hamartoma is an uncommon breast tumor that accounts for approximately 4.8% of all benign breast masses. The pathogenesis is still poorly understood and breast hamartoma is not a well-known disorder, so its diagnosis is underestimated by clinicians and pathologists. This study was designed to present our experience with breast hamartoma, along with a literature review.

METHOD: We reviewed the demographic data, pathologic analyses and imaging and results of patients diagnosed with breast hamartoma between December 2003 and September 2013.

RESULTS: In total, 27 cases of breast hamartoma operated in the Ankara University Medicine Faculty's Department of General Surgery were included in the study. All patients were female and the mean age was 41.8±10.8 years. The mean tumor size was 3.9±2.7 cm. Breast ultrasound was performed on all patients before surgery. The most common additional lesion was epithelial hyperplasia (22.2%). Furthermore, lobular carcinoma in situ was identified in one case and invasive ductal carcinoma was observed in another case. Immunohistochemical staining revealed myoid hamartoma in one case (3.7%).

CONCLUSION: Breast hamartomas are rare benign lesions that may be underdiagnosed because of the categorization of hamartomas as fibroadenomas by pathologists. Pathologic examinations can show variability from one case to another. Thus, the true incidence may be higher than the literature indicates.}, } @article {pmid25136527, year = {2014}, author = {Nigam, JS and Yadav, P and Sood, N}, title = {A retrospective study of clinico-pathological spectrum of carcinoma breast in a West Delhi, India.}, journal = {South Asian journal of cancer}, volume = {3}, number = {3}, pages = {179-181}, pmid = {25136527}, issn = {2278-330X}, abstract = {BACKGROUND: Data on the demographic profile of breast cancer patients from Delhi is scarce and whatever is available is from higher referral center. Our hospital caters to patients from an urban population of the lower socioeconomic strata and is a representation of cases at a tertiary care hospital in west Delhi. In Delhi, breast cancer (26.8%) is commonest cancer among the female followed by cervix (12.5%), gallbladder (7.2%), ovary (7.1%), and uterus (3.3%).

AIMS AND OBJECTIVES: A retrospective audit of breast cancer patients presenting at a tertiary referral center from 2004 to 2011.

MATERIALS AND METHODS: A total of 328 cases diagnosed as carcinoma breast on histopathology from year 2004 to 2011 were retrieved and studied retrospectively with regards to demographic profile and their histological features with estrogen receptor (ER), progesterone receptor (PR), and Her2neu status.

RESULTS: The median age of presentation was 49 years of age. Infiltrating ductal carcinoma (IDC, not otherwise specified (NOS)) was the commonest histopathological variant (81.40%) followed by medullary carcinoma (10.36%) and mucinous carcinoma (2.74%). Triple negative were found to be the commonest group comprising 39.4% of all the cases followed by ER and PR both positive. Pathological tumor, node, and metastasis (TNM) staging showed most common group was T2N0M0 (19.5%) followed by T2N1M0 (17.1%) and T2N2M0 (14%).

CONCLUSION: The incidence of breast cancer in the India and include a higher incidence of ER, PR, and Her2neu negative disease in west Delhi.}, } @article {pmid25130542, year = {2015}, author = {Yang, J and Zhu, J and He, K and Zhao, LY and Liu, LY and Song, TS and Huang, C}, title = {Proteomic Profiling of Invasive Ductal Carcinoma (IDC) using Magnetic Beads-based Serum Fractionation and MALDI-TOF MS.}, journal = {Journal of clinical laboratory analysis}, volume = {29}, number = {4}, pages = {321-327}, pmid = {25130542}, issn = {1098-2825}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood ; Blood Proteins/metabolism ; Breast Neoplasms/*blood/*metabolism/pathology ; Carcinoma, Ductal, Breast/*blood/*metabolism/pathology ; Case-Control Studies ; Chemical Fractionation ; Chromatography, Affinity ; Chromatography, Ion Exchange ; Female ; Humans ; *Magnetic Phenomena ; Microspheres ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Proteomics/*methods ; Quality Control ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {AIM: To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs.

METHODS: We used two different kinds of magnetic beads (magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early stage (stages I-II) IDC and 32 healthy control serum samples for proteomic profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using ClinProTools software, distinguished between IDC patients and healthy individuals based on k-nearest neighbor genetic algorithm.

RESULTS: The serum samples purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC-Cu group. The samples purified by MB-WCX had better average peak numbers, higher peak intensities, and better capturing ability of low abundance proteins or peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification methods, followed MALDI-TOF MS identification and use of ClinProTools software accurately distinguished patients with early stage IDC from healthy individuals.

CONCLUSION: Serum proteomic profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of patients with IDC in China.}, } @article {pmid25129506, year = {2014}, author = {Guiu, S and Wolfer, A and Jacot, W and Fumoleau, P and Romieu, G and Bonnetain, F and Fiche, M}, title = {Invasive lobular breast cancer and its variants: how special are they for systemic therapy decisions?.}, journal = {Critical reviews in oncology/hematology}, volume = {92}, number = {3}, pages = {235-257}, doi = {10.1016/j.critrevonc.2014.07.003}, pmid = {25129506}, issn = {1879-0461}, mesh = {Breast Neoplasms/*diagnosis/mortality/*pathology/therapy ; Carcinoma, Lobular/*diagnosis/mortality/*pathology/therapy ; Female ; Genetic Testing ; Genomics ; Humans ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Treatment Outcome ; }, abstract = {The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60-70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer.}, } @article {pmid25124574, year = {2014}, author = {Chim-ong, A and Thawornkuno, C and Chavalitshewinkoon-Petmitr, P and Punyarit, P and Petmitr, S}, title = {SLC35B2 expression is associated with a poor prognosis of invasive ductal breast carcinoma.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {15}, pages = {6065-6070}, doi = {10.7314/apjcp.2014.15.15.6065}, pmid = {25124574}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Carcinoma, Lobular/genetics/secondary ; DNA-Binding Proteins/*genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Membrane Transport Proteins/*genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms/*drug therapy/pathology ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfate Transporters ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets.

MATERIALS AND METHODS: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR).

RESULTS: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III+IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer.}, } @article {pmid25123803, year = {2014}, author = {Tajti, J and Pieler, J and Simonka, Z and Paszt, A and Lázár, G}, title = {[Treatment of pregnancy-associated breast cancer].}, journal = {Magyar sebeszet}, volume = {67}, number = {4}, pages = {268-270}, doi = {10.1556/MaSeb.67.2014.4.5}, pmid = {25123803}, issn = {0025-0295}, mesh = {Adult ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Axilla ; Biopsy, Needle/instrumentation ; Breast Neoplasms/*diagnosis/pathology/*therapy ; Carcinoma, Ductal, Breast/*diagnosis/pathology/*therapy ; *Cesarean Section ; Chemotherapy, Adjuvant ; Female ; Groin ; Humans ; Lymph Node Excision ; *Mastectomy, Segmental ; Myxoma/surgery ; Neoplasm Grading ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis/*therapy ; Radiotherapy, Adjuvant ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {CASE REPORT: A 25-year-old primipara, in the thirty-second week of her pregnancy observed a nodule in the upper outer quadrant of her left breast during self-examination. Complex breast examination revealed calcification with 4 cm of diameter. Ductal malignant cells (C5) were identified by fine-needle aspiration biopsy, while core biopsy verified invasive ductal carcinoma, grade III (B5b). No manifestations of metastases were presented. After pregnancy termination wide excision with additional axillary sentinel lymph node biopsy was performed. Because of its positivity block dissection of axillary lymph nodes was carried out. The surgical therapy was followed by adjuvant chemo-, radio- and hormonal therapy. Later an angiomyxoma appeared in the right inguinal region, which was excised in toto.

DISCUSSION: The incidence of pregnancy related malignant diseases is increasing, of which breast cancer predominates. Breast cancer, which is diagnosed during pregnancy or within the first year of delivery is called pregnancy-associated breast cancer. Because of the physiological changes in pregnancy the recognition of the disease is difficult. Therapy is complex, as besides the treatment of the mother, the safety of the fetus should be emphasized. The treatment strategies are different in the three trimesters. The surgical treatment can be performed during the whole pregnancy. The use of radiotherapy is controversial, because of teratogenic effects, while chemotherapy is permitted in the second and third trimesters. Nearly three years after the operation, our patient does not have any symptoms, her son is healthy.}, } @article {pmid25121413, year = {2014}, author = {Kitasato, Y and Yasunaga, M and Okuda, K and Kinoshita, H and Tanaka, H and Okabe, Y and Kawahara, A and Kage, M and Kaida, H and Ishibashi, M}, title = {Maximum standardized uptake value on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography and glucose transporter-1 expression correlates with survival in invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {43}, number = {7}, pages = {1060-1065}, pmid = {25121413}, issn = {1536-4828}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/chemistry/*diagnostic imaging/mortality/surgery ; ErbB Receptors/analysis ; Female ; Fluorine Radioisotopes/*pharmacokinetics ; Fluorodeoxyglucose F18/*pharmacokinetics ; Glucose Transporter Type 1/*analysis ; Glucose Transporter Type 3/analysis ; Humans ; Male ; Middle Aged ; *Multimodal Imaging ; Neoplasm Proteins/*analysis ; Pancreatectomy ; Pancreatic Neoplasms/chemistry/*diagnostic imaging/mortality/surgery ; Pancreaticoduodenectomy ; *Positron-Emission Tomography ; Preoperative Care ; Radiopharmaceuticals/*pharmacokinetics ; Retrospective Studies ; Single-Blind Method ; Survival Analysis ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVES: The purpose of this study was to assess the correlations among the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma of the pancreas.

METHODS: A total of 41 patients with surgically resected and histologically proven invasive ductal carcinoma of the pancreas who underwent preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was performed for GLUT-1, glucose transporter 3, and EGFR.

RESULTS: Higher FDG uptake (SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter overall survival (P < 0.05). The SUVmax was not found to be significantly correlated with clinicopathological characteristics such as TNM classification, lymph node metastasis, and tumor differentiation. The EGFR expression was significantly correlated with the SUVmax (P = 0.024).

CONCLUSIONS: Higher FDG uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems to be an important prognostic factor. In addition, the EGFR expression was significantly correlated with the SUVmax.}, } @article {pmid25120811, year = {2014}, author = {Cao, YW and Wan, GX and Zhao, CX and Hu, JM and Li, L and Liang, WH and Li, WQ and Li, YC and Li, YX and Du, XM and Yu, SY and Li, F}, title = {Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {7}, pages = {4286-4294}, pmid = {25120811}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Receptor, Notch1/*genetics ; Risk Factors ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression.}, } @article {pmid25119504, year = {2014}, author = {Wang, J and Zhang, X and He, J and Yang, M and Tang, J and Li, X and Tang, H and Xie, X}, title = {Co-expression of EGFR and CK5/6 in primary squamous cell carcinoma of the breast.}, journal = {Medical oncology (Northwood, London, England)}, volume = {31}, number = {9}, pages = {172}, pmid = {25119504}, issn = {1559-131X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/*metabolism ; Breast Neoplasms/epidemiology/*metabolism/mortality ; Carcinoma, Squamous Cell/epidemiology/*metabolism/mortality ; ErbB Receptors/analysis/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; }, abstract = {Primary squamous cell carcinoma of the breast (PSCCB) is an extremely rare breast tumor lacking hormone receptors and HER2 expression. However, in comparison with triple-negative invasive ductal carcinoma (TN-IDC), little is known about the PSCCB. Twenty-nine patients with PSCCB in Sun Yat-sen University Cancer Center from 1995 to 2010 were recruited in this study, along with 681 cases of TN-IDC during the same period. The clinicopathologic features and prognosis of PSCCB compared to TN-IDC were assessed. Furthermore, biomarkers of EGFR, CK5/6, E-cadherin, VEGF, TOPII, and p53 were immunostained to investigate the prognostic determinant of PSCCB. Patients with PSCCB were older than those with TN-IDC (P = 0.009) and presented with lower lymph node involvement (P = 0.015). There was no difference in overall survival (OS) between PSCCB and TN-IDC. However, the disease-free survival (DFS) of PSCCB was poorer than that of TN-IDC (P = 0.007). Multivariate analysis revealed that combined over-expression of EGFR and CK5/6 was the only independent prognostic factor for OS of PSCCB (HR 6.08, 95 % CI 1.33-27.85, P = 0.020) and associated with lymphatic metastasis (P = 0.023) and p53 expression (P = 0.013). Other predictors for poorer OS and DFS were lymphatic metastasis and stage III, which failed to show significance after multivariate analysis. Furthermore, platinum-based chemotherapy was identified to improve the OS of PSCCB with EGFR + CK5/6+ (P = 0.027). The prognosis of PSCCB is poorer than that of TN-IDC. As the only independent prognostic factor for PSCCB, combined over-expression of EGFR and CK5/6 might be a potential indicator for the use of platinum-based chemotherapy.}, } @article {pmid25119012, year = {2014}, author = {Colović, M and Todorović, M and Colović, N and Terzic, T and Karadzic, K and Jurišić, V}, title = {Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {65}, number = {1}, pages = {66-69}, doi = {10.5114/pjp.2014.42672}, pmid = {25119012}, issn = {1233-9687}, mesh = {*Adenocarcinoma/complications/genetics/metabolism ; Anemia, Aplastic/*complications ; *Breast Neoplasms/complications/genetics/metabolism ; *Carcinoma, Ductal, Breast/complications/genetics/metabolism ; Estrogens/*metabolism ; Female ; Gene Amplification ; Humans ; Middle Aged ; Receptor, ErbB-2/*genetics ; }, abstract = {Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56-year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence.}, } @article {pmid25118162, year = {2014}, author = {Reyna, C and Lee, MC and Frelick, A and Khakpour, N and Laronga, C and Kiluk, JV}, title = {Axillary burden of disease following false-negative preoperative axillary evaluation.}, journal = {American journal of surgery}, volume = {208}, number = {4}, pages = {577-581}, doi = {10.1016/j.amjsurg.2014.05.015}, pmid = {25118162}, issn = {1879-1883}, mesh = {Axilla ; Biopsy, Fine-Needle/*methods ; Breast Neoplasms/diagnosis/*secondary/surgery ; Diagnosis, Differential ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes/*diagnostic imaging/*pathology ; Lymphatic Metastasis ; Neoplasm Staging/methods ; Predictive Value of Tests ; Preoperative Period ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*methods ; Ultrasonography ; }, abstract = {BACKGROUND: Preoperative axillary ultrasound (AUS) and fine-needle aspiration (FNA) are sensitive and specific for breast cancer nodal metastases. We hypothesize that false-negative result predicts minimal axillary disease (≤2 +nodes).

METHODS: A retrospective review of breast cancer patients receiving AUS identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi-square analysis was performed using Fisher's exact test.

RESULTS: Of 903 AUS cases, 384 had T1/T2 tumors. False-negative rate of AUS ± FNA was 48% and 45%, respectively. Of 384 cases, 73 were sentinel node positive and had axillary dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non-IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3 positive nodes versus 10 (55.5%) non-IDC (P = .05) patients.

CONCLUSION: The high negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA interpretation may be better limited to the ipsilateral nodes of IDC.}, } @article {pmid25114977, year = {2014}, author = {Li, J and Xing, F and You, Z}, title = {An efficient image compressor for charge coupled devices camera.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {840762}, pmid = {25114977}, issn = {1537-744X}, mesh = {Algorithms ; Data Compression/*methods ; Image Processing, Computer-Assisted/*methods ; Models, Theoretical ; }, abstract = {Recently, the discrete wavelet transforms- (DWT-) based compressor, such as JPEG2000 and CCSDS-IDC, is widely seen as the state of the art compression scheme for charge coupled devices (CCD) camera. However, CCD images project on the DWT basis to produce a large number of large amplitude high-frequency coefficients because these images have a large number of complex texture and contour information, which are disadvantage for the later coding. In this paper, we proposed a low-complexity posttransform coupled with compressing sensing (PT-CS) compression approach for remote sensing image. First, the DWT is applied to the remote sensing image. Then, a pair base posttransform is applied to the DWT coefficients. The pair base are DCT base and Hadamard base, which can be used on the high and low bit-rate, respectively. The best posttransform is selected by the l p -norm-based approach. The posttransform is considered as the sparse representation stage of CS. The posttransform coefficients are resampled by sensing measurement matrix. Experimental results on on-board CCD camera images show that the proposed approach significantly outperforms the CCSDS-IDC-based coder, and its performance is comparable to that of the JPEG2000 at low bit rate and it does not have the high excessive implementation complexity of JPEG2000.}, } @article {pmid25112791, year = {2015}, author = {Klomek, AB and Lev-Wiesel, R and Shellac, E and Hadas, A and Berger, U and Horwitz, M and Fennig, S}, title = {The relationship between self-injurious behavior and self-disclosure in adolescents with eating disorders.}, journal = {Eating and weight disorders : EWD}, volume = {20}, number = {1}, pages = {43-48}, pmid = {25112791}, issn = {1590-1262}, mesh = {Adolescent ; Child ; Feeding and Eating Disorders/complications/*psychology ; Female ; Humans ; *Self Disclosure ; Self-Injurious Behavior/complications/*psychology ; Young Adult ; }, abstract = {PURPOSE: The aim of the current study is to examine the association between self disclosure and self-injurious behaviors among adolescent patients diagnosed with an eating disorder.

METHODS: Sixty three female patients who fulfilled the DSM-IV diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia, binge eating disorder and eating disorders not otherwise specified). Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82). Participants completed self- report questionnaires about eating disorders, self-disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS: 82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative relationship was found between general disclosure to parents and self-injurious behaviors indicating that patients who generally self-disclose to their parents (on different topics, apart from suicidal ideation) engage less frequently in self-injurious behaviors. In addition, the more patients self-disclose their suicidal ideation to others, the more they tend to self-injure.

CONCLUSION: Self-disclosure to parents on any topic may buffer against self-injurious behaviors and therefore it is important to work with adolescents suffering from eating disorders on effective self disclosure. In addition, self-disclosure about suicidal ideation to others by adolescents suffering from eating disorders should always be taken seriously, since it may be related to self-injurious behaviors.}, } @article {pmid25112709, year = {2014}, author = {Son, SH and Kim, DH and Hong, CM and Kim, CY and Jeong, SY and Lee, SW and Lee, J and Ahn, BC}, title = {Prognostic implication of intratumoral metabolic heterogeneity in invasive ductal carcinoma of the breast.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {585}, pmid = {25112709}, issn = {1471-2407}, mesh = {Breast Neoplasms/*diagnostic imaging/*metabolism/mortality ; Carcinoma, Ductal, Breast/*diagnostic imaging/*metabolism/mortality ; Female ; Fluorodeoxyglucose F18 ; Humans ; Multimodal Imaging ; Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: The purpose of this study was to evaluate the prognostic implication of findings of intratumoral metabolic heterogeneity on pretreatment (18)F-FDG PET/CT scans in patients with invasive ductal carcinoma (IDC) of the breast.

METHODS: One hundred and twenty-three female IDC patients who underwent pretreatment 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans were retrospectively evaluated in this study. The heterogeneity factor (HF) defined as the derivative (dV/dT) of a volume threshold function from 40% to 80%, was computed for each primary tumor. Other metabolic PET parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were measured. The HF was compared with clinicopathologic factors and other PET parameters. Univariate and multivariate analyses for the overall survival (OS) were performed.

RESULTS: The HF ranged from 0.02 to 6.72 (mean, 0.35 ± 0.82) and significantly correlated with MTV (r = 0.955; p < 0.0001) and TLG (r = 0.354; p = 0.0001). The HF was significantly higher (implying more heterogeneity) in tumors with higher T and N stages. The optimal cut-off values for the OS determined using a receiver operating characteristic (ROC) curve were 0.34 for the HF, 5.6 for SUVmax, 8.55 cm(3) for MTV, and 14.43 for TLG. The OS rate among the 123 patients was 86.2%. T stage (1, 2 vs. 3, 4), N stage (0, 1 vs. 2, 3), M stage (0 vs. 1), ER status (+ vs. -), SUVmax (≤ 5.6 vs. > 5.6), MTV (≤ 8.55 cm(3) vs. > 8.55 cm(3)), TLG (≤ 14.43 vs. > 14.43), and HF (< 0.34 vs. ≥ 0.34) affected the OS on univariate analysis. After adjustment for the effects of TNM stage and ER status, the HF and MTV were significant predictors of OS. Among the PET parameters, the best prognostic factor for OS was the HF.

CONCLUSIONS: Intratumoral metabolic heterogeneity correlated closely with the MTV and significantly affected the OS in IDC patients. The HF may act as a robust surrogate marker for the prediction of OS in IDC patients.}, } @article {pmid25110741, year = {2014}, author = {Li, J and Xing, F and Sun, T and You, Z}, title = {Multispectral image compression based on DSC combined with CCSDS-IDC.}, journal = {TheScientificWorldJournal}, volume = {2014}, number = {}, pages = {738735}, pmid = {25110741}, issn = {1537-744X}, mesh = {Algorithms ; *Data Compression ; *Image Processing, Computer-Assisted ; Signal Processing, Computer-Assisted ; }, abstract = {Remote sensing multispectral image compression encoder requires low complexity, high robust, and high performance because it usually works on the satellite where the resources, such as power, memory, and processing capacity, are limited. For multispectral images, the compression algorithms based on 3D transform (like 3D DWT, 3D DCT) are too complex to be implemented in space mission. In this paper, we proposed a compression algorithm based on distributed source coding (DSC) combined with image data compression (IDC) approach recommended by CCSDS for multispectral images, which has low complexity, high robust, and high performance. First, each band is sparsely represented by DWT to obtain wavelet coefficients. Then, the wavelet coefficients are encoded by bit plane encoder (BPE). Finally, the BPE is merged to the DSC strategy of Slepian-Wolf (SW) based on QC-LDPC by deep coupling way to remove the residual redundancy between the adjacent bands. A series of multispectral images is used to test our algorithm. Experimental results show that the proposed DSC combined with the CCSDS-IDC (DSC-CCSDS)-based algorithm has better compression performance than the traditional compression approaches.}, } @article {pmid25109497, year = {2014}, author = {Tanaka, N and Yoshida, H and Suzuki, Y and Harigaya, K}, title = {Relative expression of hMena11a and hMenaINV splice isoforms is a useful biomarker in development and progression of human breast carcinoma.}, journal = {International journal of oncology}, volume = {45}, number = {5}, pages = {1921-1928}, doi = {10.3892/ijo.2014.2591}, pmid = {25109497}, issn = {1791-2423}, mesh = {Alternative Splicing/genetics ; Biomarkers ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Microfilament Proteins/*biosynthesis/genetics ; Neoplasm Staging ; Protein Isoforms/*biosynthesis ; RNA, Messenger/*biosynthesis ; }, abstract = {Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. hMena has been shown to have several splice variants, including the hMena(INV) isoform, expressed in invasive cancer cells, and the epithelial-specific isoform, hMena(11a). We assessed the relative mRNA expression of hMena splice variants in 50 cases of invasive ductal breast carcinoma of no special type (IDC-NST) and 45 cases of ductal breast carcinoma in situ (DCIS) with special reference to non-neoplastic breast epithelial tissues. The samples were dissected from their respective regions by laser microdissection. Our results confirmed previous reports that hMena(INV) expression is augmented during tumor progression, while hMena(11a) is downregulated. Furthermore, simultaneous expression of hMena(11a) and hMena(INV) was found only in malignant lesions, while their expression was hardly detected in normal breast tissue and benign proliferative breast lesions. These results indicate that the higher relative expression of hMena(11a) compared with hMena(INV) may predict malignant transformation in breast epithelial cells, and, furthermore, a reversal of expression of hMena(11a) and hMena(INV) may dictate the state of cancer progression. Here, we demonstrate that determination of hMena(11a) and hMena(INV) expression could be a useful biomarker for predicting malignant behavior in breast epithelial lesions, and show that their relative expression is linked to adverse prognostic factors. Although the biological activity of the majority of alternatively spliced isoforms and their contribution to cancer biology has yet to be determined, their elucidation will have a large impact on therapeutic strategies for cancer.}, } @article {pmid25100562, year = {2014}, author = {Arthur, LM and Turnbull, AK and Webber, VL and Larionov, AA and Renshaw, L and Kay, C and Thomas, JS and Dixon, JM and Sims, AH}, title = {Molecular changes in lobular breast cancers in response to endocrine therapy.}, journal = {Cancer research}, volume = {74}, number = {19}, pages = {5371-5376}, doi = {10.1158/0008-5472.CAN-14-0620}, pmid = {25100562}, issn = {1538-7445}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics ; Carcinoma, Lobular/*drug therapy/genetics ; Cohort Studies ; Female ; Humans ; Letrozole ; Nitriles/*therapeutic use ; Postmenopause ; Triazoles/*therapeutic use ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor-positive (ER(+)) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment.}, } @article {pmid25097518, year = {2014}, author = {Hong, L and Tang, S}, title = {Does HPV 16/18 infection affect p53 expression in invasive ductal carcinoma? An experimental study.}, journal = {Pakistan journal of medical sciences}, volume = {30}, number = {4}, pages = {789-792}, pmid = {25097518}, issn = {1682-024X}, abstract = {Objective : To determine the relations between human papilloma viruses type 16 and type 18 infection and the expression of p53 protein in invasive ductal carcinoma. Methods : We detected the expression of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma in 45 cases, breast fibroadenoma in 20 cases and normal breast tissues in 20 cases. HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization and p53 protein expression was evaluated by immunohistochemistry. Results : The expression rate of HPV 16/18 DNA and p53 protein in invasive ductal carcinoma is significantly higher than those in breast fibroadenoma and normal breast tissues (p<0.05); the expression in cases with axillary lymph node metastasis is dramatically higher than those without (p<0.05); the expression of p53 protein increases with TMN staging advance. The expression of HPV16/18 DNA was significantly correlated with the expression of p53 protein (p<0.05). Conclusion : Both HPV16/18 infection and p53 mutation participate the occurrence and progress of invasive ductal carcinoma, and HPV 16/18 infection may be the major factor to cause p53 mutation.}, } @article {pmid25088444, year = {2014}, author = {Gunawardena, D and Tresham, J and Hardie, M and Phillips, M and Wylie, E}, title = {Suspicious mammographic parenchymal abnormalities that are occult at ultrasonography.}, journal = {Journal of medical imaging and radiation oncology}, volume = {58}, number = {6}, pages = {668-673}, doi = {10.1111/1754-9485.12216}, pmid = {25088444}, issn = {1754-9485}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/*methods ; Breast Neoplasms/*diagnosis ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; *Stereotaxic Techniques ; Ultrasonography, Mammary/*methods ; }, abstract = {AIM: The study aims to ascertain the significance of ultrasonically occult but mammographically suspicious parenchymal abnormalities, detected at screening mammography.

METHOD: A retrospective analysis was made on BreastScreen Western Australia data from January 2004 to December 2009. The study group included cases with a mammographic parenchymal abnormality, a negative ultrasound scan and a biopsy under stereotactic guidance. A comparable group of ultrasonically visible carcinomas was used as the control to compare with breast carcinomas in the study sample.

RESULTS: Study population consisted of 469 cases. Twenty per cent (n = 92) of the cases were breast carcinomas, with invasive ductal carcinoma (non-specified) being the most common histological type. There was a statistically significant increase in ductal carcinoma in situ and mucinous carcinoma within this malignant subgroup. Three per cent (n = 17) of the total cohort were borderline lesions on histology. The other 77% (n = 360) of cases were benign histology on core biopsy; however, one was subsequently diagnosed as an interval breast carcinoma.

CONCLUSION: Stereotactic-guided core biopsy of a suspicious mammographic parenchymal abnormality is warranted, regardless of a normal ultrasound scan, as up to 20% of these cases could be breast carcinomas.}, } @article {pmid25086552, year = {2014}, author = {Liu, H and Liu, Y and Zhao, Z and Zhang, L and Qiu, T}, title = {A new background distribution-based active contour model for three-dimensional lesion segmentation in breast DCE-MRI.}, journal = {Medical physics}, volume = {41}, number = {8}, pages = {082303}, doi = {10.1118/1.4886295}, pmid = {25086552}, issn = {2473-4209}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Breast/*pathology ; Breast Cyst/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cohort Studies ; Datasets as Topic ; Fibroadenoma/pathology ; Humans ; Imaging, Three-Dimensional/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Pattern Recognition, Automated/methods ; Phyllodes Tumor/pathology ; Young Adult ; }, abstract = {PURPOSE: To develop and evaluate a computerized semiautomatic segmentation method for accurate extraction of three-dimensional lesions from dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) of the breast.

METHODS: The authors propose a new background distribution-based active contour model using level set (BDACMLS) to segment lesions in breast DCE-MRIs. The method starts with manual selection of a region of interest (ROI) that contains the entire lesion in a single slice where the lesion is enhanced. Then the lesion volume from the volume data of interest, which is captured automatically, is separated. The core idea of BDACMLS is a new signed pressure function which is based solely on the intensity distribution combined with pathophysiological basis. To compare the algorithm results, two experienced radiologists delineated all lesions jointly to obtain the ground truth. In addition, results generated by other different methods based on level set (LS) are also compared with the authors' method. Finally, the performance of the proposed method is evaluated by several region-based metrics such as the overlap ratio.

RESULTS: Forty-two studies with 46 lesions that contain 29 benign and 17 malignant lesions are evaluated. The dataset includes various typical pathologies of the breast such as invasive ductal carcinoma, ductal carcinoma in situ, scar carcinoma, phyllodes tumor, breast cysts, fibroadenoma, etc. The overlap ratio for BDACMLS with respect to manual segmentation is 79.55% ± 12.60% (mean ± s.d.).

CONCLUSIONS: A new active contour model method has been developed and shown to successfully segment breast DCE-MRI three-dimensional lesions. The results from this model correspond more closely to manual segmentation, solve the weak-edge-passed problem, and improve the robustness in segmenting different lesions.}, } @article {pmid25083488, year = {2014}, author = {Jeeravongpanich, P and Chuangsuwanich, T and Komoltri, C and Ratanawichitrasin, A}, title = {Histologic evaluation of sentinel and non-sentinel axillary lymph nodes in breast cancer by multilevel sectioning and predictors of non-sentinel metastasis.}, journal = {Gland surgery}, volume = {3}, number = {1}, pages = {2-13}, pmid = {25083488}, issn = {2227-684X}, abstract = {Sentinel lymph node (SLN) provides accurate nodal staging for breast cancer. This technique has been introduced in Siriraj Hospital since 1998. The goal of this study is to assess its accuracy in predicting the state of the axilla, and compare the results of standard examination and multilevel sectioning. A retrospective analysis of 195 breast cancer patients who underwent both SLN biopsy (using dye alone as the lymphatic mapping) and axillary node dissection during 1998-2002 were analyzed. All slides including SLNs and the non-SLNs (NSLNs) were reviewed and multilevel study was performed on all SLNs and NSLNs [four levels of hematoxylin-eosin (HE) at 200 µm interval and keratin stains on the first and fourth levels]. Of 195 patients, 30% of cases were SLN-positive (32 NSLN-positive and 27 NSLN-negative). Additional study could detect positive axillary nodes 10.8% (4 SLN-positive and 5 NSLN-positive) more than standard HE stain. The false negative rate increased from 20.3% to 24.1%. The concordance between SLN and NSLN statuses was 89.7%. The sensitivity was 75.9%. By multivariate analysis, the significant predictors for axillary node metastasis were tumor size of more than 2.2 cm, histologic type of invasive ductal carcinoma (IDC), not otherwise specified (NOS) and lymphovascular invasion (LVI). By univariable analysis, the significant predictors of NSLN metastasis after positive-SLN were outer location of the tumor, LVI and perinodal extension. In conclusion, use of multilevel and immunohistochemistry increased detection of positive-SLNs. Caution should be kept in accepting SLN biopsy using peritumoral dye technique alone as the procedure for staging due to a high false-negative rate. The concordance rate of 89.7% confirmed the reliability of SLN. Outer location of tumor, LVI and perinodal extension is significant predictors of positive-NSLN after positive-SLN.}, } @article {pmid25081092, year = {2014}, author = {Picillo, M and Barone, P and Amboni, M and Moccia, M and Pellecchia, MT}, title = {Comment on Szewczyk-Krolikowski et al.: the influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.}, journal = {Parkinsonism & related disorders}, volume = {20}, number = {11}, pages = {1319-1320}, doi = {10.1016/j.parkreldis.2014.03.014}, pmid = {25081092}, issn = {1873-5126}, mesh = {Female ; Humans ; Male ; Parkinson Disease/*complications/*epidemiology ; }, } @article {pmid25077370, year = {2014}, author = {Bartova, M and Ondrias, F and Muy-Kheng, T and Kastner, M and Singer, Ch and Pohlodek, K}, title = {COX-2, p16 and Ki67 expression in DCIS, microinvasive and early invasive breast carcinoma with extensive intraductal component.}, journal = {Bratislavske lekarske listy}, volume = {115}, number = {7}, pages = {445-451}, doi = {10.4149/bll_2014_088}, pmid = {25077370}, issn = {0006-9248}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Cohort Studies ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclooxygenase 2/*metabolism ; Early Detection of Cancer ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Invasiveness/pathology/physiopathology ; Neoplasm Proteins/*metabolism ; Neoplasm Staging ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Recent studies have showed a significant association between the combination of COX-2, p16 and Ki67 overexpression and incidence of subsequent invasive carcinoma in a subgroup of treated ductal carcinoma in situ (DCIS) and the indicated prognostic value of COX-2, p16 and Ki67 in early breast cancer. Based on the continual model of carcinogenesis and the mentioned results, we hypothesize, that if COX-2, p16 and Ki67 expression is prognostic for DCIS future behaviour, the expression level of the markers correlates also with different stages of breast carcinomas such as DCIS, microinvasive cancer and early invasive cancer with an extensive intraductal compound. The aim of this study was to compare the expression of COX-2, p16 and Ki67 in different stages of breast carcinoma such as pure DCIS, microinvasive cancer (T1mic) and invasive ductal carcinoma with an extensive intraductal component (IDC with EIC). The expression was assessed only in in situ component of the three subgroups (DCIS, T1mic, EIC) in order to show a possible correlation of COX-2, p16 and Ki67 with different stages of carcinogenesis.

METHODS: We carried out a retrospective study using immunohistochemical staining to evaluate the expression of the markers COX-2, p16 and Ki67 in in situ lesions within three subgroups of tumors with the rising extant of invasive compound: in pure DCIS, microinvasive carcinoma (T1mic) and invasive carcinoma with extensive in situ component (IDC with EIC). Additionally, we performed a correlation analysis between the tumor subgroups and patients history data (age, parity, age of menarche, family and personal cancer history, breast feeding lengths, contraception intake, chest irradiation) as well as some of the tumor characteristics (tumor grade, multicentricity, necrosis).

RESULTS: Distribution of p16 expression differed significantly among the three diagnoses. P16 score 1 was highest in the DCIS group whereas the lowest proportion was in IDC and p16 overexpression (score 2, 3) maintained this tendency (overexpression proportion in DCIS < T1mic < IDC), though this was not significant. The frequency of COX-2 and p16 overexpression (phenotype COX-2+p16+) was higher in EIC within invasive carcinoma in comparison to DCIS and T1mic and was rising gradually with the severity of the diagnosis (proportion in DCIS < T1mic < IDC).

CONCLUSION: This is the first published study ever assessing the expression of COX-2, p16 and Ki67 markers in different breast tumors containing DCIS compound. Our results showed an increasing expression pattern of COX-2 and p16 with the rising severity of the diagnosis (expression was measured exclusively in in situ lesions within tumors containing different extant of invasiveness). The same relationship was showed for p16 marker alone. These data support different expression pattern of COX-2 and p16 markers in combination and p16 marker alone in "in situ lesions" according to the stage of carcinogenesis. This fact might be useful in the evaluation of further behaviour of early breast tumors (Tab. 3, Fig. 8, Ref. 29).}, } @article {pmid25076063, year = {2015}, author = {Türker, K and Albayrak, M and Öksüzoğlu, B and Balc, E and Oğan, MC and Iskender, G and Altuntaş, F}, title = {Entecavir as a first-line treatment for hepatitis B virus reactivation following polychemotherapy for chronic lymphocytic leukemia and invasive ductal carcinoma: a report of two cases and review of the literature.}, journal = {European journal of gastroenterology & hepatology}, volume = {27}, number = {1}, pages = {39-45}, doi = {10.1097/MEG.0000000000000115}, pmid = {25076063}, issn = {1473-5687}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/*therapeutic use ; Breast Neoplasms/complications/*drug therapy ; Carcinoma, Ductal, Breast/complications/*drug therapy ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Hepatitis B, Chronic/blood/complications/*drug therapy ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*drug therapy ; Male ; Middle Aged ; Recurrence ; Virus Activation ; }, abstract = {OBJECTIVE: Hepatitis B reactivation has been reported in chronic carriers of hepatitis B [hepatitis B surface antigen (HBsAg)] or in patients with prior hepatitis B virus (HBV) infection who are HBsAg-negative and have antibodies against hepatitis B core antigen (anti-HBc) with or without antibodies to HBsAg (anti-HBs). Lamivudine has been the first and commonly used nucleoside analog to inhibit HBV replication; however, prolonged therapy has been associated with an increased risk for drug-resistant mutations and mortality rates. Entecavir, a deoxyguanosine analog, offers several advantages over lamivudine for the treatment of HBV reactivation following chemotherapy while exhibiting more potent antiviral activity and a lower resistance rate.

METHODS: Herein, we report rapid and sustained suppression of polychemotherapy-related HBV reactivation by entecavir administered as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma. A review of the literature is discussed.

RESULTS: Entecavir produced a rapid and sustained suppression of polychemotherapy-related HBV reactivation as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma.

CONCLUSION: Allowing a rapid and sustained control of HBV replication, entecavir seems to be a promising drug for first-line prompt treatment of HBV reactivation in patients undergoing chemotherapy for hematological as well as solid organ malignancies, with safe long-term use enabling maintenance of resolved hepatitis.}, } @article {pmid25074542, year = {2014}, author = {Xiang, DB and Wei, B and Abraham, SC and Huo, L and Albarracin, CT and Zhang, H and Babiera, G and Caudle, AS and Akay, CL and Rao, P and Zhao, YJ and Lu, X and Wu, Y}, title = {Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.}, journal = {Human pathology}, volume = {45}, number = {9}, pages = {1951-1956}, doi = {10.1016/j.humpath.2014.06.002}, pmid = {25074542}, issn = {1532-8392}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Neuroendocrine/*genetics/pathology ; *Chromosome Aberrations ; Chromosome Banding/methods ; Chromosomes, Human, Pair 12/*genetics ; Chromosomes, Human, Pair 7/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping/methods ; Middle Aged ; Trisomy ; }, abstract = {Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.}, } @article {pmid25064063, year = {2014}, author = {Tong, LC and Silar, P and Lalucque, H}, title = {Genetic control of anastomosis in Podospora anserina.}, journal = {Fungal genetics and biology : FG & B}, volume = {70}, number = {}, pages = {94-103}, doi = {10.1016/j.fgb.2014.07.006}, pmid = {25064063}, issn = {1096-0937}, mesh = {Fungal Proteins/genetics/*metabolism ; *Gene Expression Regulation, Fungal ; Hyphae/genetics/*physiology ; Microscopy/methods ; Mutation ; Podospora/genetics/*physiology ; Signal Transduction ; }, abstract = {We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.}, } @article {pmid25063898, year = {2013}, author = {Villalón-López, JS and Souto-del Bosque, R and Alonso-Briones, MV and Trujillo-de Anda, AP}, title = {[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].}, journal = {Cirugia y cirujanos}, volume = {81}, number = {4}, pages = {328-332}, pmid = {25063898}, issn = {2444-054X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Capecitabine ; Carcinosarcoma/*pathology/secondary/therapy ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Docetaxel ; Fatal Outcome ; Female ; Fluorouracil/administration & dosage/analogs & derivatives ; Humans ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis ; Mastectomy ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local ; Paclitaxel/administration & dosage ; Palliative Care ; Taxoids/administration & dosage ; Gemcitabine ; }, abstract = {BACKGROUND: breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67.

CLINICAL CASE: we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease.

CONCLUSIONS: metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.}, } @article {pmid25063009, year = {2015}, author = {Namm, JP and Mueller, J and Kocherginsky, M and Kulkarni, S}, title = {The utility of sentinel lymph node biopsy in patients with ductal carcinoma in situ suspicious for microinvasion on core biopsy.}, journal = {Annals of surgical oncology}, volume = {22}, number = {1}, pages = {59-65}, doi = {10.1245/s10434-014-3943-8}, pmid = {25063009}, issn = {1534-4681}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Sentinel Lymph Node Biopsy/*statistics & numerical data ; }, abstract = {BACKGROUND: When microinvasion cannot be ruled out on core needle biopsy (CNB) in the setting of ductal carcinoma in situ (DCIS), the surgeon must decide whether to perform a sentinel lymph node biopsy (SLNB) at the time of surgery. Up to 10 % of patients with T1mi have nodal disease, but the utility of SLNB in DCIS suspicious for microinvasion (Smic) is unclear.

METHODS: The University of Chicago pathology database was queried for a diagnosis of Smic or definite microinvasion (Mic) on CNB from 2000 to 2014. We analyzed histology, imaging, core needle size, and the use of myoepithelial immunohistochemistry (IHC) markers.

RESULTS: We identified 103 women, 72 with Smic and 31 with Mic on CNB. After surgery, 32 % of Smic patients had infiltrating ductal carcinoma (IDC). Seventy-two percent of Smic patients underwent SLNB, with 67 % performed at the initial surgery. SLNB was positive in 6 % and 10 % of Smic and Mic patients, respectively (p = 0.66). Excluding N1mic, the incidence of macrometastatic nodal disease was 1.9 % for Smic patients and 3.3 % for Mic patients (p = 1.00). For Smic patients, IDC was associated with a larger lesion size and smaller CNB needle. In the setting of Smic, grade, necrosis, or presence of a mass did not increase the risk of IDC.

CONCLUSIONS: In patients with Smic on CNB, the incidence of macrometastatic nodal disease after SLNB is rare. Surgeons may consider omitting SLNB until IDC is definitively confirmed, especially in patients with Smic apart from other high-risk features.}, } @article {pmid25062930, year = {2014}, author = {Birnbaum, GE and Ein-Dor, T and Reis, HT and Segal, N}, title = {Why do men prefer nice women? Gender typicality mediates the effect of responsiveness on perceived attractiveness in initial acquaintanceships.}, journal = {Personality & social psychology bulletin}, volume = {40}, number = {10}, pages = {1341-1353}, doi = {10.1177/0146167214543879}, pmid = {25062930}, issn = {1552-7433}, mesh = {Adult ; Female ; *Gender Identity ; Humans ; *Interpersonal Relations ; Male ; Sex Factors ; *Sexual Behavior ; *Social Perception ; Young Adult ; }, abstract = {Responsiveness may signal to a potential partner that one is concerned with her or his welfare, and may therefore increase sexual interest in this person. Research shows, however, that this proposition holds true for men, but not for women. In three studies, one observational and two experimental, we explored a potential mechanism that explains why men and women diverge in their sexual reactions to a responsive opposite-sex stranger. Studies 1 and 2 showed that men, but not women, perceived a responsive stranger as more gender typical (masculine/feminine) and, in turn, as more attractive. Study 3 revealed that responsiveness increased men's perception of partner's femininity. This, in turn, was associated with higher sexual arousal, which was, in turn, linked to greater partner attractiveness and greater desire for a long-term relationship. These findings suggest that whether responsiveness affects perceptions of partner attractiveness varies in individuals, depending on the contextually based meaning of responsiveness.}, } @article {pmid25059790, year = {2015}, author = {Yajima, R and Fujii, T and Yanagita, Y and Fujisawa, T and Miyamoto, T and Hirakata, T and Tsutsumi, S and Iijima, M and Kuwano, H}, title = {Prognostic value of extracapsular invasion of axillary lymph nodes combined with peritumoral vascular invasion in patients with breast cancer.}, journal = {Annals of surgical oncology}, volume = {22}, number = {1}, pages = {52-58}, doi = {10.1245/s10434-014-3941-x}, pmid = {25059790}, issn = {1534-4681}, mesh = {Adenocarcinoma/mortality/*secondary/therapy ; Adenocarcinoma, Scirrhous/mortality/*secondary/therapy ; Axilla ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Papillary/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/mortality/*pathology/therapy ; Neoplasm Staging ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence.

METHODS: We evaluated 154 women with histologically proven node-positive breast cancer who were diagnosed with invasive ductal carcinoma, and investigated the relationships between ECI and recurrences and other clinicopathological factors, particularly vascular invasion and the number of lymph node metastases.

RESULTS: The presence of ECI at positive nodes was significantly associated with the number of positive nodes, and with disease recurrence and survival in univariate (but not multivariate) analysis. Interestingly, all ECI(+) patients with distant metastases in our series had peritumoral vascular invasion (PVI), which may have reflected systemic disease; ECI with PVI of the primary tumor strongly predicted recurrent disease and shorter survival.

CONCLUSION: ECI of axillary metastases combined with PVI indicates high tumor aggressiveness. Patients with ECI and PVI may be considered for stronger adjuvant therapies because of their high risk for distant recurrences.}, } @article {pmid25053597, year = {2014}, author = {Kim, YH and Jung, WH and Koo, JS}, title = {Expression of metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {10}, pages = {10381-10393}, pmid = {25053597}, issn = {1423-0380}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Tissue Array Analysis ; }, abstract = {The purpose of this study is to investigate the difference in expression of metabolism-related proteins in invasive lobular carcinoma (ILC) compared to those of the invasive ductal carcinoma (IDC). Tissue microarray was manufactured for 114 cases of ILC and 692 cases of IDC. Immunohistochemical stains were performed as follows: glycolysis (Glut-1, hexokinase II, CAIX, MCT4), glutaminolysis (GLS1, GDH, ASCT2), mitochondria (ATP synthase, SDHA, SDHB), and serine/glycine metabolism (PHGDH, PSAT1, PSPH, SHMT1, GLDC) related proteins. Pleomorphic type (n = 12) of ILC revealed higher expression in hexokinase II, SDHB, and GLDC than classic type (n = 102) (p < 0.05). IDC showed a higher expression of glycolysis (Glut-1, CAIX, MCT4), glutaminolysis (GLS1, ASCT2), and serine/glycine metabolism (PSPH, SHMT1, GLDC) related protein than ILC in tumor cells, whereas ILC revealed higher expression in GDH, SDHA, PHGDH, and PSAT1 than IDC in tumor cells (p < 0.05). In addition, IDC demonstrated a higher expression of metabolism-related proteins than ILC in stromal tissue (p < 0.05). In ILC, tumoral GLDC positivity was correlated with higher nuclear grade (p = 0.026) and higher histologic grade (p = 0.026), and tumoral Glut-1 positivity correlated with higher histologic grade (p = 0.026). Additionally, tumoral PSPH positivity showed a significant correlation to ER negativity and PR negativity (p = 0.026). In conclusion, it reveals different expression patterns of metabolism-related proteins between IDC and ILC.}, } @article {pmid25049275, year = {2014}, author = {Frittoli, E and Palamidessi, A and Marighetti, P and Confalonieri, S and Bianchi, F and Malinverno, C and Mazzarol, G and Viale, G and Martin-Padura, I and Garré, M and Parazzoli, D and Mattei, V and Cortellino, S and Bertalot, G and Di Fiore, PP and Scita, G}, title = {A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination.}, journal = {The Journal of cell biology}, volume = {206}, number = {2}, pages = {307-328}, pmid = {25049275}, issn = {1540-8140}, mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cell Line, Tumor ; Disease Progression ; Extracellular Matrix/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Invasiveness/genetics ; Neoplasm Recurrence, Local/genetics/pathology ; Proteolysis ; Transplantation, Heterologous ; rab5 GTP-Binding Proteins/*genetics/metabolism/*physiology ; }, abstract = {The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5-dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program.}, } @article {pmid25047051, year = {2014}, author = {Hadiji, N and Previnaire, JG and Benbouzid, R and Robain, G and Leblond, C and Mieusset, R and Enjalbert, M and Soler, JM}, title = {Are oxybutynin and trospium efficacious in the treatment of detrusor overactivity in spinal cord injury patients?.}, journal = {Spinal cord}, volume = {52}, number = {9}, pages = {701-705}, doi = {10.1038/sc.2014.113}, pmid = {25047051}, issn = {1476-5624}, mesh = {Adult ; Benzilates/*therapeutic use ; Female ; Humans ; Male ; Mandelic Acids/*therapeutic use ; Nortropanes/*therapeutic use ; Retrospective Studies ; Spinal Cord Injuries/*complications ; Time Factors ; Treatment Outcome ; Urinary Bladder, Overactive/*drug therapy/*etiology ; Urodynamics ; Urological Agents/*therapeutic use ; }, abstract = {OBJECTIVES: To evaluate the efficacy of anticholinergic agents in the treatment of neurogenic overactive bladder (NOAB) and neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients on clean intermittent catheterisation (CIC).

METHODS: Chronic suprasacral SCI patients on CIC presenting with at least one urinary leakage a day were included. Urodynamics and voiding diaries were performed at baseline and 1 month follow-up. In case of NDO at baseline, an anticholinergic drug was prescribed.

RESULTS: The 231 SCI patients presented with one to five urinary leakages per day (mean 2.1). Urodynamics showed NDO in all patients. A new anticholinergic treatment was started in all, either in monotherapy (134 patients) or in association with the existing anticholinergic drug (oxybutynin+trospium bitherapy, 97 patients). The mean maximum bladder capacity significantly increased from 225 to 441 ml, and the mean involuntary detrusor contractions (IDC) significantly decreased from 67 to 41 cm H2O. Only 75 SCI patients (32%) were fully continent. However, 25 out of these 75 patients showed persistent NDO, with amplitudes of IDC above 40 cm H2O in 12 patients. Incontinence was still found in 156 SCI patients (67%), with an average of 1,2 leakages a day. In 100 patients, amplitudes of IDC remained above 40 cm H2O. There was no statistical difference between patients on anticholinergic monotherapy or bitherapy at follow-up.

CONCLUSION: Anticholinergic treatment is not always satisfactory in terms of control of NDO and rarely allows full continence. Urodynamic follow-up is mandatory in all patients, even in those showing clinical continence.}, } @article {pmid25041824, year = {2014}, author = {Piscuoglio, S and Ng, CK and Martelotto, LG and Eberle, CA and Cowell, CF and Natrajan, R and Bidard, FC and De Mattos-Arruda, L and Wilkerson, PM and Mariani, O and Vincent-Salomon, A and Weigelt, B and Reis-Filho, JS}, title = {Integrative genomic and transcriptomic characterization of papillary carcinomas of the breast.}, journal = {Molecular oncology}, volume = {8}, number = {8}, pages = {1588-1602}, pmid = {25041824}, issn = {1878-0261}, mesh = {Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Papillary/*genetics/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics/physiology ; Genomics/*methods ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Papillary carcinoma (PC) is a rare type of breast cancer, which comprises three histologic subtypes: encapsulated PC (EPC), solid PC (SPC) and invasive PC (IPC). Microarray-based gene expression and Affymetrix SNP 6.0 gene copy number profiling, and RNA-sequencing revealed that PCs are luminal breast cancers that display transcriptomic profiles distinct from those of grade- and estrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs), and that the papillary histologic pattern is unlikely to be underpinned by a highly recurrent expressed fusion gene or a highly recurrent expressed mutation. Despite displaying similar patterns of gene copy number alterations, significant differences in the transcriptomic profiles of EPCs, SPCs and IPCs were found, and may account for their different histologic features.}, } @article {pmid25039415, year = {2014}, author = {Golland, Y and Keissar, K and Levit-Binnun, N}, title = {Studying the dynamics of autonomic activity during emotional experience.}, journal = {Psychophysiology}, volume = {51}, number = {11}, pages = {1101-1111}, doi = {10.1111/psyp.12261}, pmid = {25039415}, issn = {1540-5958}, mesh = {Adult ; Autonomic Nervous System/*physiology ; Electrocardiography ; Emotions/*physiology ; Female ; Galvanic Skin Response/*physiology ; Heart Rate/physiology ; Humans ; Male ; Young Adult ; }, abstract = {Recent theories emphasize the dynamic aspects of emotions. However, the physiological measures and the methodological approaches that can capture the dynamics of emotions are underdeveloped. In the current study, we investigated whether moment-to-moment changes in autonomic nervous system (ANS) activity are reliably associated with the unfolding of emotional experience. We obtained cardiovascular and electrodermal signals from participants while they viewed emotional movies. We found that the ANS signals were temporally aligned across individuals, indicating a reliable stimulus-driven response. The degree of response reliability was associated with the emotional time line of the movie. Finally, individual differences in ANS response reliability were strongly correlated with the subjective emotional responses. The current research offers a methodological approach for studying physiological responses during dynamic emotional situations.}, } @article {pmid25037963, year = {2014}, author = {Hadar, L and Sood, S}, title = {When knowledge is demotivating: subjective knowledge and choice overload.}, journal = {Psychological science}, volume = {25}, number = {9}, pages = {1739-1747}, doi = {10.1177/0956797614539165}, pmid = {25037963}, issn = {1467-9280}, mesh = {Adult ; *Choice Behavior ; Female ; Humans ; Male ; Middle Aged ; Motivation ; Personal Satisfaction ; *Self Concept ; Young Adult ; }, abstract = {People find it appealing to have more options to choose from, but the provision of choice often leads to adverse consequences for decision makers' motivation, satisfaction, and willingness to act. We propose that the effect of the number of choice options on willingness to purchase is moderated by people's subjective knowledge (SK). The results of three studies provide converging evidence that, paradoxically, people who feel unknowledgeable (low-SK people) in a certain domain are especially willing to purchase when more choice options are available, which is consistent with the notion of "more is better." This pattern is reversed for people who feel knowledgeable (high-SK people), which is consistent with prior evidence for choice overload. We also show that this pattern is influenced by the informativeness of the features of the available choice options and that subjective knowledge mediates this effect.}, } @article {pmid25036908, year = {2015}, author = {Kitahashi, T and Takahashi, M and Imai, T}, title = {Biphasic Alterations in Expression and Subcellular Localization of MUC1 in Pancreatic Ductal Carcinogenesis in Syrian Hamsters.}, journal = {Pancreas}, volume = {44}, number = {1}, pages = {76-86}, doi = {10.1097/MPA.0000000000000178}, pmid = {25036908}, issn = {1536-4828}, mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Carcinoma, Pancreatic Ductal/chemically induced/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/metabolism/pathology ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Mesocricetus ; Mucin-1/genetics/*metabolism ; Neoplasms, Experimental/chemically induced/genetics/*metabolism/pathology ; Nitrosamines ; Oligonucleotide Array Sequence Analysis ; RNA Interference ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Transfection ; }, abstract = {OBJECTIVES: The aim of the present study was to characterize molecular targets for the prevention/diagnosis of pancreatic cancer using a chemically induced hamster pancreatic carcinogenesis model, in which background injuries to the parenchyma, for example, chronic pancreatitis or acinar atrophy, are limited.

METHODS: Gene expression profiles in atypical hyperplasias were first investigated using a microarray technique. Immunohistochemical analyses of early lesions and invasive ductal carcinoma (IDC) were then conducted for MUC1, of which mRNA levels were prominent among the up-regulated genes, in contrast with the coexpression of epithelial-mesenchymal transition (EMT)-related proteins.

RESULTS: Immunohistochemistry for MUC1 cytoplasmic domain (MUC1-CD), which was not detected in normal-like pancreatic ducts, was positive in the apical surfaces of the epithelia of hyperplasias with and without atypia and IDC areas with distinct tubular patterns. In contrast, cytoplasmic/nuclear positivity for MUC1-CD was observed in the invasive front of IDCs. The coexpression of EMT-related proteins, such as slug and vimentin, with cytoplasmic/nuclear MUC1-CD was also detected.

CONCLUSIONS: Alterations in the expression and subcellular localization of MUC1 represent a biphasic phenomenon, and the latter may be associated with EMT in pancreatic carcinogenesis in hamsters, which indicates that changes in MUC1 are important targets for pancreatic cancer prevention and chemotherapy.}, } @article {pmid25035665, year = {2014}, author = {Zhong, J and Di, L and Zheng, W}, title = {Synchronous breast cancer and breast lymphoma: two case reports and literature review.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {26}, number = {3}, pages = {355-359}, pmid = {25035665}, issn = {1000-9604}, abstract = {Synchronous breast cancer and breast lymphoma are rare. It is of high rate of misdiagnosis in clinical practice. Here we present two cases with this presentation. They are both middle-aged women, with stage I invasive ductal carcinoma of the breast. One patient happened to have primary breast lymphoma (PBL); the other was secondary breast lymphoma (SBL). Their pathology and immunohistochemistry (IHC) findings supported the diagnosis of multiple primary carcinoma. Both patients had a surgery. Then they both received CHOP regime chemotherapy and subsequent endocrine therapy.}, } @article {pmid25034897, year = {2014}, author = {Cilia, R and Akpalu, A and Sarfo, FS and Cham, M and Amboni, M and Cereda, E and Fabbri, M and Adjei, P and Akassi, J and Bonetti, A and Pezzoli, G}, title = {The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa.}, journal = {Brain : a journal of neurology}, volume = {137}, number = {Pt 10}, pages = {2731-2742}, pmid = {25034897}, issn = {1460-2156}, mesh = {Adult ; Africa South of the Sahara ; Age of Onset ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antiparkinson Agents/*adverse effects/*therapeutic use ; Cohort Studies ; Cross-Sectional Studies ; Data Interpretation, Statistical ; Disease Progression ; Dyskinesia, Drug-Induced/physiopathology ; Female ; Ghana ; Humans ; Italy ; Levodopa/*adverse effects/*therapeutic use ; Longitudinal Studies ; Male ; Middle Aged ; Neurologic Examination ; Parkinson Disease/*drug therapy/physiopathology ; Prospective Studies ; Young Adult ; }, abstract = {During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. Study design included a cross-sectional case-control analysis of data collected between December 2008 and November 2012, and a prospective study of patients followed-up for at least 6 months after the initiation of levodopa therapy. Ninety-one patients fulfilled criteria for clinical diagnosis of idiopathic Parkinson's disease (58 males, mean age at onset 60.6 ± 11.3 years). Demographic data were compared to those of 2282 consecutive Italian patients recruited during the same period, whereas nested matched subgroups were used to compare clinical variables. Demographic features, frequency and severity of motor and non-motor symptoms were comparable between the two populations, with the only exception of more frequent tremor-dominant presentation in Ghana. At baseline, the proportion of Ghanaian patients with motor fluctuations and dyskinesias was 56% and 14%, respectively. Although levodopa therapy was introduced later in Ghana (mean disease duration 4.2 ± 2.8 versus 2.4 ± 2.1 years, P < 0.001), disease duration at the occurrence of motor fluctuations and dyskinesias was similar in the two populations. In multivariate analysis, disease duration and levodopa daily dose (mg/kg of body weight) were associated with motor complications, while the disease duration at the initiation of levodopa was not. Prospective follow-up for a mean of 2.6 ± 1.3 years of a subgroup of 21 patients who were drug-naïve at baseline [median disease duration 4.5 (interquartile range, 2.3-5) years] revealed that the median time to development of motor fluctuations and dyskinesias after initiation of levodopa therapy was 6 months. We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified.}, } @article {pmid25034035, year = {2014}, author = {Akabori, H and Shiomi, H and Naka, S and Murakami, K and Murata, S and Ishida, M and Kurumi, Y and Tani, T}, title = {Resectable carcinoma developing in the remnant pancreas 7 years and 10 months after distal pancreatectomy for invasive ductal carcinoma of the pancreas: report of a case.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {224}, pmid = {25034035}, issn = {1477-7819}, mesh = {Carcinoma, Pancreatic Ductal/*etiology/secondary/*surgery ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Second Primary/*etiology ; *Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Prognosis ; Reoperation ; }, abstract = {BACKGROUND: Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is one of the most lethal and aggressive malignancies. Operative resection remains the only treatment providing prolonged survival, however, recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of patients with pancreatic cancer within 2 years of a potential curative resection. There are few reports of pancreatic carcinoma recurrence (primary second cancer) in the remnant pancreas after pancreatectomy.

CASE PRESENTATION: A 52-year-old woman underwent a distal pancreatectomy for pancreatic cancer in September 2004. Adjuvant chemotherapy was started after surgery and continued for 4 years. In March 2012, marked elevation of DUPAN-II was observed, followed by an irregular stenotic finding in the main duct. We performed an en bloc resection of the remnant pancreas in July 2012. Histologically, the tumor contained a second primary pancreatic carcinoma with lymph node metastasis. At follow-up 20 months after the second operation, the patient was alive without recurrence. Fourteen cases of resectable cancer developing in the remnant pancreas after a pancreatectomy for cancer have been reported; a minority of these was identified as second primary tumors. Therefore, our patient's primary second cancer is a rare event.

CONCLUSION: The patient is considered to have shown a rare, unique pancreatic cancer recurrence. Persistent elevation of a tumor marker and extensive imaging led to proper diagnosis and treatment.}, } @article {pmid25032037, year = {2014}, author = {Rosiak, J and Humphreys, C}, title = {A case of complicated survivorship care.}, journal = {Journal of the advanced practitioner in oncology}, volume = {5}, number = {1}, pages = {64-68}, pmid = {25032037}, issn = {2150-0878}, abstract = {At age 34, Ms. P., a premenopausal African American woman, was diagnosed with stage IA poorly differentiated invasive ductal carcinoma of the left breast. Her tumor was estrogen and progesterone receptor (PR) positive but HER2 negative. Ms. P.'s treatment included a partial mastectomy, radiation therapy, and 2 years of tamoxifen, although tamoxifen was discontinued due to pregnancy. She was then lost to follow-up. At age 40, Ms. P. discovered a mass in her left breast upon self- exam. There was a delay in diagnosis due to pregnancy, which was terminated. A core biopsy was performed, and the pathology was positive for poorly differentiated invasive ductal carcinoma that was ER and PR positive but HER2 negative. She was clinically stage IIIB, with the tumor fixed to the chest wall. Ms. P.'s family history included premenopausal breast cancer in her mother, three of her maternal aunts, and her maternal grandmother. Genetic testing was performed; she was found to have a BRCA2 deleterious mutation. After an intrauterine device (IUD) was placed to prevent pregnancy, Ms. P. began neoadjuvant chemotherapy consisting of doxorubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 4 cycles. She then underwent a left salvage mastectomy and sentinel lymph node biopsy. After treatment, she was assessed at pathologic stage IA. Tamoxifen was reinitiated. After completing treatment, Ms. P. presented for a survivorship visit accompanied by her fiancé.}, } @article {pmid25031766, year = {2014}, author = {Cha, YJ and Kim, YH and Cho, NH and Koo, JS}, title = {Expression of autophagy related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {6}, pages = {3389-3398}, pmid = {25031766}, issn = {1936-2625}, mesh = {Adult ; Aged ; Apoptosis Regulatory Proteins/analysis/biosynthesis ; *Autophagy ; Beclin-1 ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Proteins/analysis/biosynthesis ; Microtubule-Associated Proteins/analysis/biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Phenotype ; Proportional Hazards Models ; RNA-Binding Proteins/analysis/biosynthesis ; Tissue Array Analysis ; }, abstract = {The aim of this study is to compare the expression of autophagy related proteins in invasive lobular carcinoma (ILC) with that of autophagy related proteins in invasive ductal carcinoma (IDC), and to determinate its implication. Tissue microarray containing 114 ILC and 692 IDC was constructed, and immunohistochemistry was performed for autophagy related protein (beclin-1, LC3A, LC3B, p62) and Ki-67. No significant difference in expression of autophagy-related proteins between pleomorphic type (n = 12) and classic type (n = 102) of ILC was observed, whereas ILC and IDC showed distinguished features that tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 were highly expressed in IDC and tumoral BNIP3 was highly expressed in ILC (P < 0.001). Beclin-1 expression was correlated with ER negativity (P = 0.016) and TNBC type (P = 0.024). BNIP3 expression was correlated with ER positivity (p = 0.040). Using multivariate Cox analysis, shorter overall survival was associated with tumoral beclin-1 positivity (hazard ratio: 21.19, 95% CI: 1.098-409.1, P = 0.043). In conclusion, ILC and IDC showed different expression pattern of autophagy-related proteins in tumor and stroma that demonstrated by higher expression of tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 in IDC, and higher expression of tumoral BNIP3 in ILC.}, } @article {pmid25031741, year = {2014}, author = {Liu, X and Guan, Y and Zhang, W and Liu, S and Liu, J and Wang, L and Niu, Y}, title = {Predictors of recurrence in breast cancer subtypes with negative lymph node in a Chinese population.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {6}, pages = {3202-3212}, pmid = {25031741}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma/metabolism/*pathology ; Case-Control Studies ; Female ; Humans ; Ki-67 Antigen/biosynthesis ; Middle Aged ; Neoplasm Recurrence, Local/metabolism/*pathology ; Prognosis ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Retrospective Studies ; Tumor Suppressor Protein p53/biosynthesis ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {To establish a series of objective parameters to predict the risk of relapse from axillary lymph node-negative (ANN) breast cancer, and evaluate the patterns of recurrence according to molecular subtypes, we collected information on 2126 consecutive breast cancer patients operated between 2002 and 2006. In this case-control study, 212 patients experiencing recurrence or breast cancer related death were defined as 'poor group'. Another 212 patients were selected from the remaining cases with stratified sampling method to comprise the 'good group'. Significant differences were found in vascular invasion, grade and molecular subtype between the two groups. Expression of ER and PR in the 'poor group' was lower (P < 0.05). However, positive rates of Ki67, p53 and VEGF in the 'poor group' were higher (P < 0.05). Multivariate analysis revealed that molecular subtype, expression of VEGF, tumor grade, and vascular invasion were closely correlated with bad outcome. Analysis of the 'poor group' demonstrated that 'HER2 positive' and 'triple negative' subtypes more commonly suffered from distant metastases and death. No metastasis was found in patients with pure invasive papillary carcinoma, invasive cribriform carcinoma or adenoid cystic carcinoma, whereas the diagnoses of invasive micropapillary carcinoma, invasive apocrine carcinoma, invasive papillary carcinoma mixed with invasive ductal carcinoma, or metaplastic carcinoma were correlated with distant metastasis and death. In conclusion, molecular subtype and expression of VEGF are useful markers for predicting prognosis of ANN breast cancer patients. 'Luminal A-like' subtype has better outcome than others. Moreover, molecular subtypes have different recurrence patterns.}, } @article {pmid25031282, year = {2014}, author = {Croall, ID and Cowie, CJ and He, J and Peel, A and Wood, J and Aribisala, BS and Mitchell, P and Mendelow, AD and Smith, FE and Millar, D and Kelly, T and Blamire, AM}, title = {White matter correlates of cognitive dysfunction after mild traumatic brain injury.}, journal = {Neurology}, volume = {83}, number = {6}, pages = {494-501}, pmid = {25031282}, issn = {1526-632X}, mesh = {Adolescent ; Adult ; Aged ; Brain Injuries/*complications/*diagnosis ; Cognition Disorders/*diagnosis/*etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Nerve Fibers, Myelinated/*pathology ; Young Adult ; }, abstract = {OBJECTIVE: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation.

METHODS: Fifty-three patients were scanned an average of 6 days postinjury (range = 1-14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance.

RESULTS: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps.

CONCLUSIONS: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.}, } @article {pmid25030864, year = {2014}, author = {Liu, L and Zhao, Q and Liang, X and Du, G and Lu, L and Dong, J and Han, H}, title = {[Expression of neuronal marker protein gene product 9.5 and its clinicopathologic significance in breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {5}, pages = {318-320}, pmid = {25030864}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Disease-Free Survival ; Female ; Fibroadenoma/metabolism/pathology ; Humans ; Middle Aged ; Neoplasm Grading ; Ubiquitin Thiolesterase/*metabolism ; }, abstract = {OBJECTIVE: To detect the expression of pan-neuronal marker protein gene product (PGP)9.5 and its clinicopathologic significance in breast cancer.

METHODS: The expression of PGP9.5 was examined by immunohistochemistry EnVision method in 196 cases during 2007 to 2011, including 20 normal tissues, 14 cases of fibroadenoma, 18 cases of ductal carcinoma in situ (DCIS) and 144 cases of invasive ductal carcinoma (IDC) of the breast. The relationship between PGP9.5 expression and clinicopathologic characteristics of IDC was assessed.

RESULTS: PGP9.5 expression was localized in the stroma of all normal breast tissues, but there was no expression observed in all fibroadenomas and DCIS. Overall, the expression rate of PGP9.5 in IDC was 61.8% (89/144). PGP9.5 expression increased from grade 1 tumors (29.4%, 10/34) to grade 2-3 tumors (71.8%, 79/110; P = 0.000). In addition, patients with less than 3 years disease-free survival tended to show higher PGP9.5 expression (64.8%, 35/54), compared to patients with equal to and/or more than 3 years disease-free survival (46.7%, 42/90; P = 0.035). However, there was no correlation between PGP9.5 expression and tumor size, tumor stage, lymph metastasis, hormone receptor expression.

CONCLUSION: PGP9.5 expression is correlated with tumor grade and prognosis in IDC of the breast.}, } @article {pmid25029110, year = {2014}, author = {Rizwani, W and Schaal, C and Kunigal, S and Coppola, D and Chellappan, S}, title = {Mammalian lysine histone demethylase KDM2A regulates E2F1-mediated gene transcription in breast cancer cells.}, journal = {PloS one}, volume = {9}, number = {7}, pages = {e100888}, pmid = {25029110}, issn = {1932-6203}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA077301/CA/NCI NIH HHS/United States ; CA77301/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; E2F1 Transcription Factor/*genetics ; Epithelial Cells/metabolism/pathology ; F-Box Proteins/genetics/*metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism ; Matrix Metalloproteinases/metabolism ; Neoplasm Invasiveness ; Neovascularization, Pathologic/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Retinoblastoma Protein/metabolism ; *Transcription, Genetic ; Up-Regulation ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; }, abstract = {It is established that histone modifications like acetylation, methylation, phosphorylation and ubiquitination affect chromatin structure and modulate gene expression. Lysine methylation/demethylation on Histone H3 and H4 is known to affect transcription and is mediated by histone methyl transferases and histone demethylases. KDM2A/JHDM1A/FBXL11 is a JmjC-containing histone demethylase that targets mono- and dimethylated Lys36 residues of Histone H3; its function in breast cancer is not fully understood. Here we show that KDM2A is strongly expressed in myoepithelial cells (MEPC) in breast cancer tissues by immunohistochemistry. Ductal cells from ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) show positive staining for KDM2A, the expression decreases with disease progression to metastasis. Since breast MEPCs have tumor-suppressive and anti-angiogenic properties, we hypothesized that KDM2A could be contributing to some of these functions. Silencing KDM2A with small interfering RNAs demonstrated increased invasion and migration of breast cancer cells by suppressing a subset of matrix metalloproteinases (MMP-2, -9, -14 and -15), as seen by real-time PCR. HUVEC cells showed increased angiogenic tubule formation ability in the absence of KDM2A, with a concomitant increase in the expression of VEGF receptors, FLT-1 and KDR. KDM2A physically bound to both Rb and E2F1 in a cell cycle dependent manner and repressed E2F1 transcriptional activity. Chromatin immunoprecipitation (ChIP) assays revealed that KDM2A associates with E2F1-regulated proliferative promoters CDC25A and TS in early G-phase and dissociates in S-phase. Further, KDM2A could also be detected on MMP9, 14 and 15 promoters, as well as promoters of FLT1 and KDR. KDM2A could suppress E2F1-mediated induction of these promoters in transient transfection experiments. These results suggest a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function.}, } @article {pmid25027758, year = {2014}, author = {Rask, L and Balslev, E and Søkilde, R and Høgdall, E and Flyger, H and Eriksen, J and Litman, T}, title = {Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status.}, journal = {Cellular oncology (Dordrecht)}, volume = {37}, number = {3}, pages = {215-227}, pmid = {25027758}, issn = {2211-3436}, mesh = {Aged ; Blotting, Western ; Breast Neoplasms/classification/diagnosis/*genetics ; Down-Regulation ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; MicroRNAs/*genetics ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; PTEN Phosphohydrolase/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Up-Regulation ; }, abstract = {PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target PTEN.

METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry.

RESULTS: miR-486-5p and miR-139-5p were found to be down-regulated in patients with lymph node metastases, whereas miR-21 was found to be up-regulated in patients with a positive lymph node status. miR-21 expression levels were found to significantly correlate with tumour size (r = 0.403, p = 0.009; Spearman's rank), whereas no relation was found between miR-21 and PTEN expression levels (Kruskal-Wallis test).

CONCLUSION: Down-regulation of miR-486-5p and miR-139-5p, in conjunction with up-regulation of miR-21, may represent a useful signature for the identification of high-risk breast cancer patients.}, } @article {pmid25027116, year = {2014}, author = {Ramalho, EA and Silva-Filho, JL and Cartaxo, MF and Cavalcanti, CB and Rêgo, MJ and Oliveira, MB and Beltrão, EI}, title = {Assessment of changes in the BRCA2 and P53 genes in breast invasive ductal carcinoma in northeast Brazil.}, journal = {Biological research}, volume = {47}, number = {1}, pages = {3}, pmid = {25027116}, issn = {0717-6287}, mesh = {Alleles ; Brazil ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; CpG Islands/genetics ; DNA Methylation/*genetics ; Female ; *Genes, BRCA2 ; *Genes, p53 ; Genotype ; Humans ; Mutation ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Promoter Regions, Genetic/genetics ; Risk Factors ; Statistics as Topic ; }, abstract = {BACKGROUND: BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.

RESULTS: BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.

CONCLUSIONS: There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.}, } @article {pmid25015740, year = {2014}, author = {Sperk, E and Astor, D and Keller, A and Welzel, G and Gerhardt, A and Tuschy, B and Sütterlin, M and Wenz, F}, title = {A cohort analysis to identify eligible patients for intraoperative radiotherapy (IORT) of early breast cancer.}, journal = {Radiation oncology (London, England)}, volume = {9}, number = {}, pages = {154}, pmid = {25015740}, issn = {1748-717X}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/surgery ; Cohort Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; *Intraoperative Care ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; *Patient Selection ; Prognosis ; Radiotherapy Dosage ; Survival Rate ; }, abstract = {BACKGROUND: Since the results from the randomized TARGIT A trial were published, intraoperative radiotherapy (IORT) is used more often. IORT can be provided as accelerated partial breast irradiation (APBI) or as a boost. The definition of suitable patients for IORT as APBI differs between different national societies (e.g. ESTRO and ASTRO) and different inclusion criteria of trials and so does the eligibility of patients. This analysis identifies eligible patients for IORT according to available consensus statements and inclusion criteria of the ongoing TARGIT trials.

METHODS: Between 01/03 - 12/09, 1505 breast cancer cases were treated at the breast cancer center at the University Medical Center Mannheim. Complete data sets for age, stage (T, N, and M), histology and hormone receptor status were available in 1108 cases. Parameters to identify eligible patients are as follows: ESTRO: >50 years, invasive ductal carcinoma/other favorable histology (IDC), T1-2 (≤3 cm), N0, any hormone receptor status, M0; ASTRO: ≥60 years, IDC, T1, N0, positive estrogen hormone receptor status, M0; TARGIT E "elderly", risk adapted radiotherapy with IORT followed by external beam radiotherapy in case of risk factors in final histopathology, phase II: ≥70 years, IDC, T1, N0, any hormone receptor status, M0; TARGIT C "consolidation", risk adapted radiotherapy, phase IV: ≥50 years, IDC, T1, N0, positive hormone receptor status, M0; TARGIT BQR "boost quality registry": every age, every histology, T1-2 (max. 3.5 cm), any hormone receptor status, N0/+, M0/+.

RESULTS: Out of the 1108 cases, 379 cases (34.2%) were suitable for IORT as APBI regarding the ESTRO and 175 (15.8%) regarding the ASTRO consensus statements. 82 (7.4%) patients were eligible for the TARGIT E trial, 258 (23.3%) for the TARGIT C trial and 671 (60.6%) for the TARGIT BQR registry. According to the consensus statements of ASTRO (45.1%) and ESTRO (41.4%) about half of the eligible patients were treated with IORT as APBI. From the eligible patients fulfilling the criteria for IORT boost (35%) about one third was eventually treated.

CONCLUSIONS: Patient selection for IORT should be restrictive. For IORT as APBI the TARGIT trials are even more restrictive including patients than the ESTRO and ASTRO consensus statements.}, } @article {pmid25015071, year = {2014}, author = {Ovanez, C and Crawford, J and Asarian, A and Xiao, P}, title = {Invasive ductal carcinoma of the breast with clear cell and pseudo-lactating changes.}, journal = {Journal of surgical case reports}, volume = {2014}, number = {7}, pages = {}, pmid = {25015071}, issn = {2042-8812}, abstract = {Invasive ductal carcinoma of the breast with clear cell changes is a very rare pathological entity. There are <150 cases of this breast cancer subtype reported in the literature. Clear cell carcinoma could be easily missed or under-diagnosed in a breast core biopsy specimen due to the fact that this subtype tends to show a papillary pattern with clear cell and pseudo-lactating changes, especially in young female patients. Normal breast tissue may possess clear cells as a consequence of the physiological changes of pregnancy, the clearing of the cytoplasm within myoepithelial cells, or the clearing of the cytoplasm in apocrine metaplasia. Owing to its aggressive clinical course, clear cell carcinoma must be differentiated from other subtypes of breast carcinoma. Special attention given to this rare subtype by pathologists and clinicians could avoid misdiagnosis and delay of treatment.}, } @article {pmid25014550, year = {2014}, author = {Jafferbhoy, S and Paterson, H and Fineron, P}, title = {Synchronous gist, colon and breast adenocarcinoma with double colonic polyp metastases.}, journal = {International journal of surgery case reports}, volume = {5}, number = {8}, pages = {523-526}, pmid = {25014550}, issn = {2210-2612}, abstract = {INTRODUCTION: Long term survivors of breast cancer are at risk of developing distant metastasis years after the initial treatment. We report a case of breast adenocarcinoma with colonic polyp metastases, as well as synchronous primary colonic adenocarcinoma and a gastric GIST.

PRESENTATION OF CASE: An 83 year old female underwent colonoscopy for rectal bleeding. This showed a primary colonic adenocarcinoma, a pedunculated polyp in the ascending colon and two polyps in the sigmoid colon. A staging CT scan did not show distant metastasis, but revealed a small gastric GIST which was managed conservatively. A right hemicolectomy showed a T3N0 colonic adenocarcinoma and a polyp contained metastatic adenocarcinoma from a breast primary. The patient had undergone surgery 30 years ago for an invasive lobular carcinoma. Further clinical assessment demonstrated an impalpable grade II Invasive ductal carcinoma in the contralateral breast. She was started on hormonal treatment and at 18 months follow-up, she was well with stable disease.

DISCUSSION: Invasive lobular cancer is the most common histological type of breast cancer that metastasizes to the colon. There is no consensus on the management of breast cancer metastasis to the gastrointestinal tract. Co-existence of a GIST and an adenocarcinoma at two separate locations is uncommon. These are two different cancer entities and it is unclear whether these two are related by as causal relationship.

CONCLUSION: This is a rare case of three distinct tumours; association between them is unlikely. However, the case highlights the importance of a multidisciplinary approach to cancer treatment.}, } @article {pmid25013432, year = {2014}, author = {Kim, YS and Jung, MJ and Ryu, DW and Lee, CH}, title = {Clinicopathologic characteristics of breast cancer stem cells identified on the basis of aldehyde dehydrogenase 1 expression.}, journal = {Journal of breast cancer}, volume = {17}, number = {2}, pages = {121-128}, pmid = {25013432}, issn = {1738-6756}, abstract = {PURPOSE: Breast cancer displays varying molecular and clinical features. The ability to form breast tumors has been shown by several studies with aldehyde dehydrogenase 1 (ALDH1) positive cells. The aim of this study is to investigate the association between ALDH1 expression and clinicopathologic characteristics of invasive ductal carcinoma.

METHODS: We investigated breast cancer tissues for the prevalence of ALDH1(+) tumor cells and their prognostic value. The present study included paraffin-embedded tissues of 70 patients with or without recurrences. We applied immunohistochemical staining for the detection of ALDH1(+) cells. Analysis of the association of clinical outcomes and molecular subtype with marker status was conducted.

RESULTS: ALDH1(+) and ALDH1(-) tumors were more frequent in triple-negative breast cancers and in luminal A breast cancers, respectively (p<0.01). ALDH1 expression was found to exert significant impact on disease free survival (DFS) (ALDH1(+) vs. ALDH1(-), 53.1±6.7 months vs. 79.2±4.7 months; p=0.03) and overall survival (OS) (ALDH1(+) vs. ALDH1(-), 68.5±4.7 months vs. 95.3±1.1 months; p<0.01). In triple-negative breast cancer (TNBC) patients, DFS and OS showed no statistical differences according to ALDH1 expression (ALDH1(+) vs. ALDH1(-), 45.3±9.4 months vs. 81.3±7.4 months, p=0.52; 69.0±7.5 months vs. 91.3±6.3 months, p=0.67). However, non-TNBC patients showed significant OS difference between ALDH1(+) and ALDH1(-) tumors (ALDH1(+) vs. ALDH1(-), 77.6±3.6 months vs. 98.0±1.0 months; p=0.04) with no statistical difference of DFS (ALDH1(+) vs. ALDH1(-), 60.5±8.0 months vs. 81.8±4.6 months; p=0.27).

CONCLUSION: Our findings suggest that the expression of ALDH1 in breast cancer may be associated with TNBC and poor clinical outcomes. On the basis of our findings, we propose that ALDH1 expression in breast cancer could be correlated with poor prognosis, and may contribute to a more aggressive cancer phenotype.}, } @article {pmid25012264, year = {2015}, author = {Nelson, RA and Guye, ML and Luu, T and Lai, LL}, title = {Survival outcomes of metaplastic breast cancer patients: results from a US population-based analysis.}, journal = {Annals of surgical oncology}, volume = {22}, number = {1}, pages = {24-31}, doi = {10.1245/s10434-014-3890-4}, pmid = {25012264}, issn = {1534-4681}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*mortality ; Carcinoma, Ductal, Breast/epidemiology/*mortality ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Metaplasia/epidemiology/*mortality ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Survival Rate ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Metaplastic breast cancer (MBC) is a rare histologic subtype needing further characterization. The aim of our study was to compare MBC to infiltrating ductal carcinoma (IDC) of the breast and to identify demographic, clinicopathologic, treatment, and survival differences.

METHODS: MBC and IDC patients were identified using the Surveillance, Epidemiology, and End Results (SEER) public-use data set. Disease-specific survival (DSS) differences were compared using the Kaplan-Meier method and log-rank tests. Univariate and multivariate Cox proportional hazard models were used to assess factors prognostic for DSS. To control for hormone receptor status, a subsequent planned analysis was completed for receptor-negative MBC and IDC. Lastly, a matched case-control analysis was conducted to minimize potential bias due to baseline demographic, clinical, and pathologic differences.

RESULTS: The SEER data set included 1,011 MBC and 253,818 IDC patients diagnosed from 2001 to 2010. MBC patients had larger, higher grade tumors, had less frequent axillary nodal involvement, and were more likely to be treated with mastectomy. Five-year DSS rates were significantly worse for patients with MBC than for IDC patients (78 vs. 93 %, p < 0.0001) and for patients with receptor-negative MBC than receptor-negative IDC (77 vs. 85 %, p < 0.0001). The findings were confirmed on matched analysis. Prognostic factors identified on multivariate analyses included age, MBC histology, tumor grade, T stage, and axillary lymph node involvement.

CONCLUSIONS: MBC patients have shorter DSS than IDC patients. Improved clinical and biological understanding of MBC may result in more effective therapy and better cancer outcomes.}, } @article {pmid25012047, year = {2014}, author = {Sayed, S and Moloo, Z and Wasike, R and Bird, P and Oigara, R and Govender, D and Kibera, J and Carrara, H and Saleh, M}, title = {Is breast cancer from Sub Saharan Africa truly receptor poor? Prevalence of ER/PR/HER2 in breast cancer from Kenya.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {5}, pages = {591-596}, doi = {10.1016/j.breast.2014.06.006}, pmid = {25012047}, issn = {1532-3080}, mesh = {Adenocarcinoma, Mucinous/epidemiology/*metabolism/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology/*metabolism/pathology ; Carcinoma, Lobular/epidemiology/*metabolism/pathology ; Female ; Humans ; Kenya/epidemiology ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prevalence ; Prospective Studies ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Triple Negative Breast Neoplasms/epidemiology/metabolism/pathology ; }, abstract = {OBJECTIVES: Studies on ER/PR/HER2 in breast cancer from Sub Saharan Africa (SSA) are fraught with inconsistencies in the prevalence of hormone receptor status. In Kenya, ER/PR/HER2 for breast cancers is not part of routine assessment and available in only three to four centers across the country. Variability in methodology and interpretation makes comparison between data difficult. Our aim was to accurately determine the prevalence of ER/PR/HER2 using standardized techniques and double reporting. Prognostic tumor parameters were also correlated with clinical features and receptor status.

MATERIALS AND METHODS: Consecutive invasive breast cancers (IBC) accrued between September 2011 and December 2012 were analyzed at Aga Khan University Hospital, Nairobi (AKUHN). Tumor blocks were stained for ER/PR/HER2 on an automated platform. Double reporting of ER/PR/HER2 was done using the Allred system and the ASCO/CAP guidelines respectively.

RESULTS: A total of 301 cases of IBC were analyzed for pathology and ER/PR/HER2. The age range of patients was 19-94 years with a median of 47.5 years. Invasive ductal carcinoma (NOS) was the most common histologic type (84.2%). ER positivity was seen in 72.8%, PR in 64.8% and HER2 in 17.6% of all cases. Triple negative breast cancers (TNBC) constituted 20.2% of the cases. There was a significant association between receptor status and histologic grade (p < 0.001) and statistically significant trend of increasing pathological stage of tumor (pT) associated with TNBC (p = 0.020).

CONCLUSIONS: We present a definitive prospective analysis of ER/PR/HER2 from a single center and demonstrate that prevalence of receptor status from SSA is comparable with that in the West.}, } @article {pmid25011551, year = {2014}, author = {Rodrigues, P and Hering, F and Campagnari, JC}, title = {Involuntary detrusor contraction is a frequent finding in patients with recurrent urinary tract infections.}, journal = {Urologia internationalis}, volume = {93}, number = {1}, pages = {67-73}, doi = {10.1159/000356063}, pmid = {25011551}, issn = {1423-0399}, mesh = {Adult ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Muscle Contraction ; Muscle, Smooth/physiopathology ; Prospective Studies ; Recurrence ; Surveys and Questionnaires ; Urinary Bladder/*pathology ; Urinary Bladder, Overactive/*pathology ; Urinary Incontinence, Stress/physiopathology ; Urinary Tract Infections/*pathology ; Urination Disorders/physiopathology ; Urodynamics ; Water ; }, abstract = {OBJECTIVE: To check whether subtle voiding dysfunction is related to recurrent urinary tract infection (rUTI).

METHODS: 254 consecutive patients with at least four episodes of urinary tract infection (UTI) were studied. At least three repeat urodynamic evaluations with an additional ice water test to maximize the detection of involuntary detrusor contraction (IDC) were used. Stress urinary incontinence cases were used as controls. Nonparametric univariate and multivariate analyses were used for statistics.

RESULTS: IDC was detected in 83.6% of patients in the rUTI group and in 31.7% in the control group. IDC was <15 cm H2O in 54.7% whereas high-amplitude (>50 cm H2O) IDC was observed in 6.8% in the rUTI group. Female urinary tract obstruction was diagnosed in 16.8% of patients in the rUTI group and in 7.9% in the control group. Residual volume, PdetQmax and Qmax were not predictive of UTI recurrence. Symptoms were similar in both groups.

CONCLUSIONS: Patients with rUTI present with covert bladder dysfunctions represented by detrusor overactivity.}, } @article {pmid25011545, year = {2014}, author = {Catteau, X and Simon, P and Noël, JC}, title = {Myofibroblastic stromal reaction and lymph node status in invasive breast carcinoma: possible role of the TGF-β1/TGF-βR1 pathway.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {499}, pmid = {25011545}, issn = {1471-2407}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Myofibroblasts/*cytology/*metabolism/pathology ; Protein Serine-Threonine Kinases/*metabolism ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta/*metabolism ; Signal Transduction ; Stromal Cells/metabolism/pathology ; Transforming Growth Factor beta1/*metabolism ; Tumor Microenvironment ; }, abstract = {BACKGROUND: The microenvironment modulates tissue specificity in the normal breast and in breast cancer. The stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness in breast carcinoma. The aim of the present study is to examine the stromal expression of CD34 and SMA in cases of invasive ductal carcinoma and to try to demonstrate the role played by the TGF-ß 1 et TGF-ß R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts.

METHODS: We carried out an immunohistochemical study of CD34, SMA, TGF-ß and TGF-ß R1 on a series of 155 patients with invasive ductal carcinoma. We also treated a breast fibrocytes cell line with TGF-ß1.

RESULTS: We found a loss of stromal expression of CD34 with the appearance of a myofibroblastic reaction in almost 100% cases of invasive ductal carcinoma. The strong stromal expression of SMA correlates with the presence of lymph node metastases. We were also able to show a greater expression of TGF-ß in the tumor cells as well as a higher expression of TGF- ß R1 in the tumor stroma compared to normal breast tissue. Finally, we demonstrated the transformation of breast fibrocytes into SMA positive myofibroblasts after being treated with TGF-ß1.

CONCLUSIONS: Our study demonstrated that a significant tumor myofibroblastic reaction is correlated with the presence of lymph node metastasis and that this myofibroblastic reaction can be induced by TGF-ß1. Future research on fibrocytes, myofibroblasts, TGF-ß and stromal changes mechanisms is essential in the future and may potentially lead to new treatment approaches.}, } @article {pmid25009747, year = {2014}, author = {Philippson, C and Simon, S and Vandekerkhove, C and Hertens, D and Veys, I and Noterman, D and De Neubourg, F and Larsimont, D and Bourgeois, P and Van Houtte, P and Nogaret, JM}, title = {Early invasive cancer and partial intraoperative electron radiation therapy of the breast: experience of the jules bordet institute.}, journal = {International journal of breast cancer}, volume = {2014}, number = {}, pages = {627352}, pmid = {25009747}, issn = {2090-3170}, abstract = {Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7-37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high.}, } @article {pmid25009006, year = {2014}, author = {Fujihira, A and Suzuki, T and Chang, MO and Moriyama, T and Kitajima, M and Takaku, H}, title = {Antitumor effects of baculovirus-infected dendritic cells against human pancreatic carcinoma.}, journal = {Gene therapy}, volume = {21}, number = {9}, pages = {849-854}, doi = {10.1038/gt.2014.59}, pmid = {25009006}, issn = {1476-5462}, mesh = {Animals ; Baculoviridae/physiology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Dendritic Cells/immunology/*virology ; Female ; Humans ; Immunotherapy ; Killer Cells, Natural/*immunology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms/*immunology/pathology/*therapy ; Survival Analysis ; }, abstract = {Recently, we showed that baculovirus (BV)-infected dendritic cells (DCs) (BV-DCs) induced antitumor immunity against established tumors in mice. These antitumor effects were CD8(+) T-cell and natural killer (NK) cell dependent but CD4(+) T-cell independent. In the current study, we examined the antitumor effect of BV-DCs on human pancreatic cancer cells (AsPC-1). After treatment with BV-infected bone marrow-derived dendritic cells (BMDCs), human pancreatic tumors caused by AsPC-1 cells in a nude mouse model were significantly reduced in size, and the survival of the mice was improved compared with that of non-immature BMDC (iDC)- and BV-DC-immunized mice. We also found that wild-type BV could activate human DCs (HDCs) and that NK cells were activated by BV-infected HDCs (BHDCs). Our findings show that BV-DCs can induce antitumor immunity, which paves the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.}, } @article {pmid25008065, year = {2014}, author = {Ruibal, Á and Aguiar, P and Del Río, MC and Menéndez, P and Arias, JI and Herranz, M}, title = {Positive immunohistochemical expression of bcl-2 in hormone-independent breast carcinomas is associated with a greater lymph node involvement and poor outcome.}, journal = {Medical oncology (Northwood, London, England)}, volume = {31}, number = {8}, pages = {105}, pmid = {25008065}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/mortality/*pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {To study the immunohistochemical expression of bcl-2 in patients with hormone-independent breast infiltrating ductal carcinomas (IDC) and its possible association with other clinico-biological parameters and outcome. Our study group included 72 females with hormone-independent (ER and PgR negative) infiltrating ductal breast carcinomas. Age, tumor size, axillary lymph node involvement (N), distant metastasis and histological grade, as well as the immunohistochemical expression of Ki67, p53 and androgen receptor (AR), were analyzed. We follow up 57 patients during a period of time ranged between 20 and 193 months (80.2 ± 58.3; median 78 months). Of all IDCs included in our study, 18 were ER-/PgR-/bcl-2+ and 54 ER-/PgR-/bcl-2-. The percentages of slightly bcl-2-positive (+) and bcl-2-strong positive (++) cases were 25 and 19 %, respectively, values lower than those observed in ER+/PgR+ tumors (79.3 and 86.8 %, respectively). Breast IDC with positivity (+) for bcl-2 showed, exclusively, greater lymph node involvement higher than 3 nodes (N+ >3) (p 0.021) and a great number of deaths due to the tumor (p 0.011). Same results were obtained when we compared bcl-2-negative and bcl-2-strong positive (++) subgroups. Our results led us to consider that the positive (+ or ++) immunohistochemical expression of bcl-2 in hormone-independent (ER and PgR negative) breast carcinomas is associated with greater axillary lymph node involvement and a greater number of deaths in the follow-up, being these data opposite to that observed in hormone-dependent tumors.}, } @article {pmid25007177, year = {2014}, author = {Rêgo, MJ and da Silva Filho, AF and Cordeiro, MF and Santos, PB and Beltrão, EI}, title = {The glycomic profile of invasive ductal carcinoma of the breast is altered in patients with hypoxic regions: implications for tumor behavior.}, journal = {Folia histochemica et cytobiologica}, volume = {52}, number = {2}, pages = {96-103}, doi = {10.5603/FHC.2014.0017}, pmid = {25007177}, issn = {1897-5631}, mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carbonic Anhydrases/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Case-Control Studies ; Cell Hypoxia ; Female ; Galectin 1/*genetics/metabolism ; Galectin 3/*genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Oxygen/*metabolism ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {Hypoxic areas in solid tumors are often associated with poor prognosis and resistance to chemotherapy. The aim of the study was to analyze the expression of galectin-1 (Gal-1), galectin-3 (Gal-3), sialic acid and b1-6 branched glycan structures in hypoxic environment of invasive ductal carcinoma (IDC) of the breast. We performed lectin histochemistry with phytohemag glutinin-L (L-PHA) and Sambucus nigra lectin (SNA); and immunohistochemistry for Gal-1, Gal-3, carbonic anhydrase IX, hypoxia-inducible factor, estrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor type-2 for 86 IDC samples. Patients with markers positive for hypoxia were mostly ER-negative (p = 0.003) and presented with more nodal invasion than the non-hypoxic group (p = 0.0439). Concerning the glycobiological aspects, the hypoxic group expressed more of Gal-3 (p = 0.0021) and SNA ligands (p = 0.0498), however, there was no association between lectin- and galectin-staining and clinical and histopathological data. Our results suggest a change in the glycomic profile of patients within hypoxic regions of IDC. However, further studies are needed to evaluate the role of lectin- and galectin-ligands in tumor's hypoxic environment, as well as their potential to be used as therapeutic targets.}, } @article {pmid25006633, year = {2014}, author = {Gilbert, FJ and van den Bosch, HC and Petrillo, A and Siegmann, K and Heverhagen, JT and Panizza, P and Gehl, HB and Pediconi, F and Diekmann, F and Peng, WJ and Ma, L and Sardanelli, F and Belli, P and Corcione, S and Zechmann, CM and Faivre-Pierret, M and Martincich, L}, title = {Comparison of gadobenate dimeglumine-enhanced breast MRI and gadopentetate dimeglumine-enhanced breast MRI with mammography and ultrasound for the detection of breast cancer.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {39}, number = {5}, pages = {1272-1286}, doi = {10.1002/jmri.24434}, pmid = {25006633}, issn = {1522-2586}, mesh = {Breast Neoplasms/*diagnosis ; Contrast Media ; Female ; *Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Meglumine/*analogs & derivatives ; Middle Aged ; *Organometallic Compounds ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue.

MATERIALS AND METHODS: In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3–5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared.

RESULTS: In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8–17.5%; P < 0.0001), ultrasound (Δ18.3–20.0%; P < 0.0001), and mammography and/or ultrasound (Δ8.6–10.7%; P ≤ 0.0105) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0–5.5% vs. 11.1% at mammography; 6.3–8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2–97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2–84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2–96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7–88.5% on gadopentetate dimeglumine-enhanced MRI vs. 77.0–84.4% with conventional techniques). Overall diagnostic performance for the detection of cancer was superior on gadobenate dimeglumine-enhanced MRI than on conventional imaging or gadopentetate dimeglumine-enhanced MRI.

CONCLUSION: Gadobenate dimeglumine-enhanced MRI significantly improves cancer detection compared to gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound in a selected group of patients undergoing breast MRI for preoperative staging or because of inconclusive findings at conventional imaging.}, } @article {pmid25003839, year = {2014}, author = {Harbhajanka, A and Lamzabi, I and Singh, RI and Ghai, R and Reddy, VB and Bitterman, P and Gattuso, P}, title = {Correlation of clinicopathologic parameters and immunohistochemical features of triple-negative invasive lobular carcinoma.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {22}, number = {6}, pages = {e18-26}, doi = {10.1097/PAI.0b013e3182a5a02d}, pmid = {25003839}, issn = {1533-4058}, mesh = {*Breast Neoplasms/metabolism/pathology ; *Carcinoma, Lobular/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of invasive breast carcinoma. With the advent of gene profiling, breast cancer has been classified into luminal A, luminal B, HER2-overexpressing, and triple-negative carcinoma (TNC). Several studies have described TNC (ER, PR, HER2) as a surrogate for basal-like breast carcinoma. However, there is sparse literature on triple-negative lobular carcinoma (TNLC), as most of them show hormone receptor expression. The aim of this study was to investigate the correlation of clinicopathologic parameters of TNLC that has been demonstrated in invasive ductal carcinoma.

MATERIALS AND METHODS: Clinicopathologic parameters and immunohistochemical stains for ER, PR, E-cadherin, HER2, MIB1, and fluorescent in situ hybridization for HER2 of 255 ILC cases were retrieved. In addition, immunohistochemical analysis was performed for p53, c-kit, vimentin, p16, cyclinD1, and BCL2 on 78 cases where 12 were TNC cases and 66 were non-TNC cases.

RESULTS: Of the 255 ILC cases, 218 (85.5%) were classic and 37 (14.5%) were pleomorphic. Seventy-seven (30.1%) cases showed axillary lymph node metastasis. There were 14 of the 255 TNC cases (5.49%) that showed higher incidence in the elderly patients. Six of the 37 (16.21%) cases were pleomorphic and 8 of the 218 (3.7%) cases were classic. Positivity for vimentin was seen in 8 of the 12 cases (67.7%), CK 5 in 3 of the 12 (25%) cases, p16 in 11 of the 12 (91.6%) cases, p53 in 8 of the 12 (66.7%) cases, c-kit in 6 of the 12 (50%) cases, and cyclinD1 in 6 of the 12 cases (50%) indicating basal-like phenotype in 3 cases and nonbasal-like phenotype in 9 cases. There was no statistical significance in lymph node metastasis, tumor recurrence, and distant metastasis between TNC and non-TNC.

CONCLUSIONS: TNLC showed distinct clinicopathologic features such as more frequently seen in the elderly, pleomorphic, larger tumor size, increased expression of vimentin, CK 5, p16, p53, and c-kit. Not all cases showed basal-like phenotype. TNLC is less frequently seen as compared with TNC in invasive ductal carcinoma.}, } @article {pmid25001103, year = {2014}, author = {Fang, X and Reifman, J and Wallqvist, A}, title = {Modeling metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle.}, journal = {Molecular bioSystems}, volume = {10}, number = {10}, pages = {2526-2537}, doi = {10.1039/c4mb00115j}, pmid = {25001103}, issn = {1742-2051}, mesh = {Animals ; Biomass ; Energy Metabolism ; Erythrocytes/*parasitology ; Host-Parasite Interactions ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*metabolism/*parasitology ; *Metabolic Networks and Pathways ; *Models, Biological ; Plasmodium falciparum/*growth & development/*metabolism ; Time Factors ; }, abstract = {The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic developmental cycle (IDC) in human red blood cells. A better understanding of the metabolic processes required during the asexual blood-stage reproduction will enhance our basic knowledge of P. falciparum and help identify critical metabolic reactions and pathways associated with blood-stage malaria. We developed a metabolic network model that mechanistically links time-dependent gene expression, metabolism, and stage-specific growth, allowing us to predict the metabolic fluxes, the biomass production rates, and the timing of production of the different biomass components during the IDC. We predicted time- and stage-specific production of precursors and macromolecules for P. falciparum (strain HB3), allowing us to link specific metabolites to specific physiological functions. For example, we hypothesized that coenzyme A might be involved in late-IDC DNA replication and cell division. Moreover, the predicted ATP metabolism indicated that energy was mainly produced from glycolysis and utilized for non-metabolic processes. Finally, we used the model to classify the entire tricarboxylic acid cycle into segments, each with a distinct function, such as superoxide detoxification, glutamate/glutamine processing, and metabolism of fumarate as a byproduct of purine biosynthesis. By capturing the normal metabolic and growth progression in P. falciparum during the IDC, our model provides a starting point for further elucidation of strain-specific metabolic activity, host-parasite interactions, stress-induced metabolic responses, and metabolic responses to antimalarial drugs and drug candidates.}, } @article {pmid24998964, year = {2014}, author = {Iwamoto, M and Takei, H and Iida, S and Yamashita, K and Yanagihara, K and Kurita, T and Tsuchiya, S and Kanazawa, Y and Uchida, E}, title = {Contralateral breast cancer adjacent to a fibroadenoma: report of a case.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {81}, number = {3}, pages = {168-172}, doi = {10.1272/jnms.81.168}, pmid = {24998964}, issn = {1347-3409}, mesh = {Biopsy ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Female ; Fibroadenoma/*pathology ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Second Primary/*pathology ; }, abstract = {A 64-year-old woman noticed a lump of the right breast and consulted our outpatient clinic. She had undergone multiple excisional biopsies of fibroadenomas in both breasts and mastectomy for invasive ductal carcinoma (IDC) of the left breast. After completing 5 years of treatment with adjuvant tamoxifen, she had undergone screening with annual physical examinations and occasional computed tomography. She was declared recurrence-free 13 years after breast cancer surgery, although lumps were detected in the right breast, probably due to fibroadenomas. Mammography, ultrasonography, and magnetic resonance imaging revealed that the lump was irregularly shaped, 2 cm in diameter, and adjacent to a fibroadenoma with macrocalcification. Two axillary lymph nodes were enlarged and suggestive of metastasis. A core needle biopsy revealed IDC of the right breast. She underwent a right partial mastectomy with axillary lymph node dissection. The IDC was 2 cm in diameter, of nuclear grade 2, and adjacent to a 0.7-cm fibroadenoma with a macrocalcification. The margins of the IDC close to the fibroadenoma were clearly demarcated by the fibrous capsule of the fibroadenoma. Four axillary lymph nodes were positive for metastasis. In the present case the presence of fibroadenoma might have interfered with the early detection of the contralateral IDC. The history of multiple excisions of fibroadenomas and mastectomy for breast cancer suggests an increased risk of contralateral breast cancer for the patient's entire life; therefore, regular annual follow-up, such as physical examinations and mammography, is recommended.}, } @article {pmid24997789, year = {2014}, author = {Kim, JY and Kim, YJ and Kim, SH and Kang, BJ and Song, BJ}, title = {Invasive ductal carcinoma of the breast in a 14-year-old girl.}, journal = {Pediatric radiology}, volume = {44}, number = {11}, pages = {1446-1449}, pmid = {24997789}, issn = {1432-1998}, mesh = {Adolescent ; Breast Neoplasms/genetics/*pathology/*therapy ; Carcinoma, Ductal, Breast/genetics/*pathology/*therapy ; *Chemoradiotherapy, Adjuvant ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Magnetic Resonance Imaging ; *Mastectomy, Segmental ; Neoplasm Staging ; Rare Diseases/diagnosis/genetics/therapy ; Ultrasonography, Mammary ; }, abstract = {Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer.}, } @article {pmid24996968, year = {2014}, author = {Zhao, Q and Yang, Y and Liang, X and Du, G and Liu, L and Lu, L and Dong, J and Han, H and Zhang, G}, title = {The clinicopathological significance of neurogenesis in breast cancer.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {484}, pmid = {24996968}, issn = {1471-2407}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Disease Progression ; Disease-Free Survival ; Female ; Fibroadenoma/metabolism/*pathology ; Humans ; Nerve Fibers/*metabolism ; S100 Proteins/metabolism ; Ubiquitin Thiolesterase/metabolism ; }, abstract = {BACKGROUND: Recent reports support a novel biological phenomenon about cancer related neurogenesis. However, little is known about the clinicopathological significance of neurogenesis in breast cancer.

METHODS: A total of 196 cases, including 20 of normal tissue, 14 of fibroadenoma, 18 of ductal carcinoma in situ (DCIS) and 144 of invasive ductal carcinoma (IDC) of the breast were used. The tissue slides were immunostained for protein gene product (PGP) 9.5 and S 100 to identify nerves. The correlation between the expression of PGP 9.5 and clinicopathological characteristics in IDC of the breast was assessed.

RESULTS: While the PGP 9.5 positive nerve fibers are identified in all cases of normal breast tissue controls and in the tumor stroma of 61% (89/144) cases of invasive ductal carcinomas, PGP 9.5 positive nerve fibers are not seen in the tumor stroma of cases of fibroadenoma and DCIS. The percentage of tumors that exhibited neurogenesis increased from tumor grade I to tumor grade II and III (29.4% vs 71.8%, p < 0.0001). In addition, patients with less than 3 years of disease-free survival tended to have a higher positive expression of PGP 9.5 compared to patients with an equal or more than 3 years of disease-free survival (64.8% vs 46.7%, p = 0.035). Furthermore, moderate/strong expression of PGP 9.5 was found to be significantly related to microvessel density (MVD, p = 0.014). Interestingly, PGP 9.5 expression was significantly associated with higher MVD in the ER-negative (p = 0.045) and node-negative (p = 0.039) subgroups of IDC of the breast.

CONCLUSIONS: This data indicates that neurogenesis is associated with some aggressive features of IDC including tumor grade and patient survival as well as angiogenesis, especially in ER-negative and node-negative subtypes of IDC of the breast. Thus, neurogenesis appears to be associated with breast cancer progression and may play a role in therapeutic guidance for patients with ER-negative and node-negative invasive breast cancer.}, } @article {pmid24996432, year = {2014}, author = {Asch-Kendrick, RJ and Samols, MA and Lilo, MT and Subhawong, AP and Sharma, R and Illei, PB and Argani, P and Cimino-Mathews, A}, title = {NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas.}, journal = {Journal of clinical pathology}, volume = {67}, number = {9}, pages = {768-771}, pmid = {24996432}, issn = {1472-4146}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Carcinoma, Lobular/*chemistry/secondary ; Female ; Homeodomain Proteins/*analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Androgen/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; Tissue Array Analysis ; Transcription Factors/*analysis ; Tumor Burden ; }, abstract = {AIMS: NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status.

METHODS: Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity.

RESULTS: Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1–100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age.

CONCLUSIONS: This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.}, } @article {pmid24989617, year = {2014}, author = {Saunderson, RB and Gouliouris, T and Cartwright, EJ and Nickerson, EJ and Aliyu, SH and O'Donnell, DR and Kelsall, W and Limmathurotsakul, D and Peacock, SJ and Török, ME}, title = {Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.}, journal = {BMJ open}, volume = {4}, number = {7}, pages = {e004659}, pmid = {24989617}, issn = {2044-6055}, support = {G1000803/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Bacteremia/microbiology/*therapy ; Child ; Child, Preschool ; Dimethoate ; *Disease Management ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/microbiology/*therapy ; Staphylococcus aureus/*isolation & purification ; }, abstract = {OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children.

STUDY DESIGN: Observational cohort study of children with SAB.

SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK.

PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012.

METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group.

RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4 years (IQR 0.2-10.7 years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90 days following onset of SAB.

CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.}, } @article {pmid24989112, year = {2016}, author = {Kotani, H and Yoshimura, A and Adachi, Y and Ishiguro, J and Hisada, T and Ichikawa, M and Gondou, N and Hattori, M and Kondou, N and Sawaki, M and Fujita, T and Iwata, H}, title = {Sentinel lymph node biopsy is not necessary in patients diagnosed with ductal carcinoma in situ of the breast by stereotactic vacuum-assisted biopsy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {23}, number = {2}, pages = {190-194}, doi = {10.1007/s12282-014-0546-y}, pmid = {24989112}, issn = {1880-4233}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Image-Guided Biopsy/*methods ; Lymph Nodes/diagnostic imaging/*pathology/surgery ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy/*statistics & numerical data ; Vacuum ; }, abstract = {BACKGROUND: This study evaluated the role and need of a sentinel lymph node biopsy (SLNB) in patients with an initial diagnosis of ductal carcinoma in situ (DCIS) made by stereotactic vacuum-assisted biopsy (VAB).

MATERIALS AND METHODS: A retrospective analysis was performed of 1,458 patients who underwent stereotactic VAB between January 1999 and December 2012 at Aichi Cancer Center Hospital. The rates of axillary node metastasis and the underestimation of invasive ductal carcinoma (IDC) were examined.

RESULTS: Of the 1,458 patients who underwent stereotactic VAB, 199 had a preoperative diagnosis of DCIS and underwent surgery. In these patients, 20 % (39/199) were upstaged to IDC or at least microinvasion in final pathology. Axillary lymph node status was investigated in 81 % (161/199) of initially diagnosed DCIS patients, and resulted in finding lymph node metastasis in 0.62 % (1/161) patients. To assess the potential preoperative predictors of invasiveness, the value of DCIS histological grade on biopsy samples, the distribution of calcifications on mammograms, and the combination of these factors were studied. The underestimation rate was higher (30 %) in the combination of high DCIS histological grade and extensive calcification although there was no significant association (p = 0.23).

CONCLUSION: The rate of lymph node metastasis was extremely low (0.62 %), even when invasive carcinoma was identified on excision in patients initially diagnosed with DCIS by stereotactic VAB. Because of the low prevalence of metastatic involvement, the cessation of SLNB is a reasonable consideration in patients initially diagnosed with DCIS by stereotactic VAB.}, } @article {pmid24980157, year = {2014}, author = {Ren, M and Liu, F and Zhu, Y and Li, Y and Lang, R and Fan, Y and Gu, F and Zhang, X and Fu, L}, title = {Absence of caveolin-1 expression in carcinoma-associated fibroblasts of invasive micropapillary carcinoma of the breast predicts poor patient outcome.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {465}, number = {3}, pages = {291-298}, pmid = {24980157}, issn = {1432-2307}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Papillary/chemistry/mortality/*pathology ; Caveolin 1/*analysis ; Female ; Fibroblasts/*chemistry ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {Caveolin-1 (Cav-1) expression in stromal carcinoma-associated fibroblasts (CAFs) has been associated with tumor progression and clinical outcome. This study was undertaken to assess its prognostic significance in invasive micropapillary carcinoma of the breast (IMPC), a tumor with abundant stromal CAFs and a high tendency for nodal metastasis and poor outcome. Cav-1 expression was studied by immunohistochemistry in a group of 86 cases of IMPC along with a control group of 105 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). Our results indicate that absence of Cav-1 expression in CAFs of IMPC is more common than in IDC-NOS (57 %, 49/86 vs. 36 %, 38/105). The absence of expression was associated with larger tumor size and higher lymph node stage (P < 0.05) of IMPC. Univariate analysis suggested absence of Cav-1 in CAFs to be a candidate independent predictor of reduced progression-free survival (PFS) (HR = 3.945, 95 % CI = 1.717-9.063, P = 0.001), which was confirmed by multivariable analysis (P = 0.018). In patients with IMPC spreading to local lymph nodes, loss of stromal Cav-1 predicted a fourfold increase in risk for shortened PFS. In contrast, no significant difference of tumor epithelial Cav-1 expression was found between IMPC and IDC-NOS, and the expression of tumor Cav-1 was not significantly associated with the prognosis of patients with IMPC. Absence of Cav-1 expression in CAFs is a strong prognostic factor for IMPC patients, and it may further subgroup the patients with lymph node metastasis to guide clinical management.}, } @article {pmid24980090, year = {2014}, author = {Arps, DP and Jorns, JM and Zhao, L and Bensenhaver, J and Kleer, CG and Pang, JC}, title = {Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.}, journal = {Annals of surgical oncology}, volume = {21}, number = {13}, pages = {4152-4158}, doi = {10.1245/s10434-014-3871-7}, pmid = {24980090}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; Humans ; *Mastectomy/methods ; Mastectomy, Segmental ; Michigan ; Middle Aged ; Neoplasm Staging ; Reoperation/statistics & numerical data ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies.

METHODS: Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed.

RESULTS: For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L.

CONCLUSIONS: Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.}, } @article {pmid24978026, year = {2014}, author = {Pape-Zambito, D and Jiang, Z and Wu, H and Devarajan, K and Slater, CM and Cai, KQ and Patchefsky, A and Daly, MB and Chen, X}, title = {Identifying a highly-aggressive DCIS subgroup by studying intra-individual DCIS heterogeneity among invasive breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e100488}, pmid = {24978026}, issn = {1932-6203}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; R01 CA138819/CA/NCI NIH HHS/United States ; R21 CA186853/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/complications/*diagnosis/genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Female ; Formaldehyde ; Gene Expression ; *Genetic Heterogeneity ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tissue Embedding ; Tissue Fixation ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The heterogeneity among multiple ductal carcinoma in situ (DCIS) lesions within the same patient also diagnosed with invasive ductal carcinoma (IDC) has not been well evaluated, leaving research implications of intra-individual DCIS heterogeneity yet to be explored. In this study formalin-fixed paraffin embedded sections from 36 patients concurrently diagnosed with DCIS and IDC were evaluated by immunohistochemistry. Ten DCIS lesions from each patient were then randomly selected and scored. Our results showed that expression of PR, HER2, Ki-67, and p16 varied significantly within DCIS lesions from a single patient (P<0.05 for PR; P<1×10(-8) for HER2, Ki-67 and p16). In addition, seventy-two percent of the individuals had heterogeneous expression of at least 2/6 markers. Importantly, by evaluating the expression of promising DCIS risk biomarkers (Ki-67, p53 and p16) among different DCIS subgroups classified by comparing DCIS molecular subtypes with those of adjacent normal terminal duct lobular units (TDLU) and IDC, our results suggest the existence of a highly-aggressive DCIS subgroup, which had the same molecular subtype as the adjacent IDC but not the same subtype as the adjacent normal TDLU. By using a systematic approach, our results clearly demonstrate that intra-individual heterogeneity in DCIS is very common in patients concurrently diagnosed with IDC. Our novel findings of a DCIS subpopulation with aggressive characteristics will provide a new paradigm for mechanistic studies of breast tumor progression and also have broad implications for prevention research as heterogeneous pre-invasive lesions are present in many other cancer types.}, } @article {pmid24977705, year = {2014}, author = {Shi, WB and Yang, LJ and Hu, X and Zhou, J and Zhang, Q and Shao, ZM}, title = {Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e101390}, pmid = {24977705}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Survival Analysis ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.

PATIENTS AND METHODS: A total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC) cases were included. The clinical features, breast cancer-specific survival (BCSS) and recurrence/metastasis-free survival (RFS) of the patients were compared between these two groups.

RESULTS: The IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively) than patients with IDC (89.5% and 84.5%, respectively). Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%). In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034). A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001). However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.

CONCLUSIONS: In Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.}, } @article {pmid24971211, year = {2014}, author = {Forae, G and Nwachokor, F and Igbe, A}, title = {Histopathological profile of breast cancer in an African population.}, journal = {Annals of medical and health sciences research}, volume = {4}, number = {3}, pages = {369-373}, pmid = {24971211}, issn = {2141-9248}, abstract = {BACKGROUND: Currently breast cancer (BRCA) still remain the most commonly diagnosed female cancer globally with a significant geographic, racial and ethnical variations in its incidence.

AIM: This article examines the frequency and histological types and grades of BRCA in a pioneer teaching Hospital in Delta State, Nigeria.

MATERIALS AND METHODS: H and E stained-slides of breast biopsies diagnosed at the Central Hospital, Warri from 2005 to 2011 were archived and studied. Request forms were scrutinized for clinical bio-data, diagnosis and histological sections were analyzed. Data obtained were analyzed using the Statistical Package for the Social Sciences version 17 statistical package (SPSS) Incorporated, Chicago, Illinois, USA, and value presented descriptively.

RESULTS: During this period, 905 breast lesions were seen. Out of this, 261 were BRCAs, of which 260 cases were females and one case was a male. The peak age incidence for BRCA and its variants was 40-49 years accounting for (n = 94/261; 36%). The mean age of BRCA was 46 years (6.2). Invasive carcinoma of no special type (NST) was the most commonly encountered histological group of breast carcinoma constituting (n = 203/261, 77.7%) with the high grade invasive ductal carcinoma as the leading diagnosis.

CONCLUSION: Majority of BRCAs encounter was invasive ductal carcinoma of NST with bulk of patients presenting in Stages III and IV.}, } @article {pmid24969877, year = {2014}, author = {Sharma, M and Sharma, JD and Sarma, A and Ahmed, S and Kataki, AC and Saxena, R and Sharma, D}, title = {Triple negative breast cancer in people of North East India: critical insights gained at a regional cancer centre.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {11}, pages = {4507-4511}, doi = {10.7314/apjcp.2014.15.11.4507}, pmid = {24969877}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/genetics ; Female ; Humans ; India ; Lymph Nodes/pathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Retrospective Studies ; Triple Negative Breast Neoplasms/genetics/*pathology ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed.

AIM: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) -"TNBC" and "Others".

MATERIALS AND METHODS: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others".

RESULTS: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC.

CONCLUSIONS: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.}, } @article {pmid24966964, year = {2014}, author = {Miyai, K and Divatia, MK and Shen, SS and Miles, BJ and Ayala, AG and Ro, JY}, title = {Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {5}, pages = {2518-2526}, pmid = {24966964}, issn = {1936-2625}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/blood/chemistry/mortality/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/blood/chemistry/mortality/*secondary/surgery ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kallikreins/blood ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/blood/chemistry/mortality/*secondary/surgery ; Prostatic Neoplasms/blood/chemistry/mortality/*pathology/surgery ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.}, } @article {pmid24966944, year = {2014}, author = {dos-Santos, PB and Zanetti, JS and Vieira-de-Mello, GS and Rêgo, MB and Ribeiro-Silva A, A and Beltrão, EI}, title = {Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {5}, pages = {2337-2349}, pmid = {24966944}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*enzymology/genetics/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/genetics/mortality/pathology ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; *Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; N-Acetylglucosaminyltransferases/*analysis ; Neoplasm Invasiveness ; *Plant Lectins ; Predictive Value of Tests ; Proportional Hazards Models ; *Ribosome Inactivating Proteins ; Risk Factors ; Time Factors ; Tissue Array Analysis ; }, abstract = {Increased sialylation and β1,6-branched oligosaccharides has been associated with a variety of structural changes in cell surface carbohydrates, most notably in tumorigenesis. Lectins are defined as proteins that preferentially recognize and bind carbohydrate complexes protruding from glycolipids and glycoproteins. This interaction with carbohydrates can be as specific as the interaction between antigen and antibody. Due to this type of interaction lectins have been used as experimental auxiliary tools in histopathological diagnosis of cancer. This study was designed to evaluate the differential expression of sialic acids and β1,6-N-acetylglucosaminyltransferase V (MGAT5) in invasive (IDC) and in situ (DCIS) ductal carcinoma of the breast and its possible application as prognostic biomarkers. A possible transition between pre-malign and malign lesions was evaluated using DCIS samples. Biopsies were analyzed regarding the expression of MUC1, p53, Ki-67, estrogen receptor, progesterone receptor, HER-2 and MGAT5. α2,6-linked sialic acids residues recognized by SNA lectin was overexpressed in 33.3% of IDC samples and it was related with Ki-67 (p=0.042), PR (p=0.029), lymphnodes status (p=0.017) and death (p=0.011). Regarding survival analysis SNA was the only lectin able to correlate with specific-disease survival and disease-free survival (p=0.024 and p=0.041, respectively), besides, it presents itself as an independent variable by Cox Regression analysis (p= 0.004). Comparing IDC and DCIS cases, only SNA showed different staining pattern (p=0.034). The presence of sialic acids on tumor cell surface can be an indicative of poor prognosis and our study provides further evidence that SNA lectin can be used as a prognostic probe in IDC and DCIS patients.}, } @article {pmid24964871, year = {2014}, author = {Rambau, P and Masalu, N and Jackson, K and Chalya, P and Serra, P and Bravaccini, S}, title = {Triple negative breast cancer in a poor resource setting in North-Western Tanzania: a preliminary study of 52 patients.}, journal = {BMC research notes}, volume = {7}, number = {}, pages = {399}, pmid = {24964871}, issn = {1756-0500}, mesh = {Adult ; Female ; Hospitals, Teaching/*statistics & numerical data ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Referral and Consultation/*statistics & numerical data ; Tanzania ; Triple Negative Breast Neoplasms/*diagnosis/*metabolism/therapy ; }, abstract = {BACKGROUND: Breast cancer is the second leading cancer worldwide. In Tanzania, though it ranks as the second leading cancer in women after cervical cancer, hormonal receptor status is not carried out routinely in patients. Adjuvant hormonal therapy is given without prior knowledge of hormonal receptors status and patients can incur unnecessary costs and side effects. This study was performed to investigate the expression of hormonal receptors, epidermal growth factor receptors (HER-2) and proliferation index of the breast cancer by Ki-67 in a few selected patients with breast cancer at referral hospital in North-Western Tanzania. The study classified breast cancer subtypes based on hormonal receptors status and the expression of epidermal growth factor receptors.

RESULTS: A total of 52 cases of breast cancer were investigated. Patients' mean age at diagnosis was 49 years. The majority of the tumors was invasive ductal carcinoma 47 (90.4%) and 40 (76.9%) were of histological grade III. Thirty-eight (73.1%) of the patient had lymph node metastasis at the time of diagnosis and 36 (69.2%) were at clinical stage III. Only 3 (5.8%) patients were in clinical stage I. There was a tendency of a low level of expression of the receptors, whereby Estrogen Receptor (ER) positive tumors were 17 (32.7%), progesterone receptor (PR) positive tumors were 22 (42.3%), and HER-2 positive tumors were 12 (23.1%). Triple negative tumors constituted 20 (38.4%) of the patients. Most of the tumors (75%) showed high proliferation by Ki-67. Lymph node metastasis was more common in Triple Negative and HER enriched tumors.

CONCLUSION: This study showed a tendency for a low level of expression of hormonal receptors. There was a significant proportion of Triple Negative breast cancers. Routine testing for hormonal receptors in breast cancer is recommended before the initiation of adjuvant hormonal therapy.}, } @article {pmid24959456, year = {2014}, author = {Jagtap, SV and Chougule, PG and Khatib, W and Shukla, DB and Jagtap, SS}, title = {Male breast cancer: presenting as synchronous, large, bilateral masses.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {8}, number = {4}, pages = {FD07-8}, pmid = {24959456}, issn = {2249-782X}, abstract = {Male breast cancer is a very rare neoplasm which accounts for 1% of all breast cancers. A 70-year-old male presented with a rapidly growing, bilateral breast masses with large size, surface ulceration and bloody discharge. Synchronous bilateral breast cancer was diagnosed by using fine needle aspiration cytology, mammography, ultrasonography and incisional biopsy. Histopathological studies revealed invasive ductal carcinoma (not otherwise specified), which was of grade III in left breast and of grade II in right breast. We are presenting this case with its clinico-pathological findings, as synchronous bilateral breast cancer occurs extremely rarely in males.}, } @article {pmid24959251, year = {2014}, author = {Jeong, YJ and Oh, HK and Bong, JG}, title = {Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature.}, journal = {Oncology letters}, volume = {8}, number = {1}, pages = {230-234}, pmid = {24959251}, issn = {1792-1074}, abstract = {Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association.}, } @article {pmid24959243, year = {2014}, author = {Wang, WW and Chen, L and Ouyang, XN}, title = {Misdiagnosed male breast cancer with an unknown primary tumor: A case report.}, journal = {Oncology letters}, volume = {8}, number = {1}, pages = {190-192}, pmid = {24959243}, issn = {1792-1074}, abstract = {Compared with female breast cancer, male breast cancer (MBC) has an extremely low morbidity, later staging and fewer breast tissues. The lumps are easier to invade in the center and the majority of the cases are positive for metastatic lymph node, with the typical clinical manifestation as a painless mass in partial breast. MBC with an unknown primary tumor is rare and is often prone to misdiagnosis, resulting in a delay in correct treatment. Such a case is extremely significant for clinical reference. The current study presents a 58-year-old male who developed a painless mass in the left armpit and received armpit mass biopsy and pathological examination which showed glandular cancer, with a high possibility of mammary primary tumor. The patient was administered four cycles of paclitaxel plus oxaliplatin chemotherapy. However, three months later, the patient identified novel disseminated lymph nodes in the left armpit. The initial pathological section and paraffin blocks were re-examined and the patient was finally diagnosed with breast invasive ductal carcinoma based on the metastases pathology and immunohistochemical examination. No breast mass was found on physical examination of the patient and the tumor markers, including cancer antigen 125 and carcinoembryonic antigen, were normal. No primary tumors were observed in the mammography and PET-CT and the primary tumor was not found following the left breast modified radical mastectomy.}, } @article {pmid24958347, year = {2014}, author = {Zheng, C and Liang, L and Xu, S and Zhang, H and Hu, C and Bi, L and Fan, Z and Han, B and Xu, W}, title = {The use of Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy for human breast cancer detection.}, journal = {Analytical and bioanalytical chemistry}, volume = {406}, number = {22}, pages = {5425-5432}, doi = {10.1007/s00216-014-7967-5}, pmid = {24958347}, issn = {1618-2650}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology ; DNA/chemistry ; Female ; Fibroadenoma/diagnosis/pathology ; Gold/*chemistry ; Humans ; Hyperplasia/diagnosis/pathology ; Metal Nanoparticles/*chemistry ; Middle Aged ; Nanotechnology/*methods ; Silicon Dioxide/*chemistry ; Spectrum Analysis, Raman/*methods ; Young Adult ; beta Carotene/chemistry ; }, abstract = {This study uses the powerful fingerprint features of Raman spectroscopy to distinguish different types of breast tissues including normal breast tissues (NB), fibroadenoma (FD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Thin frozen tissue sections of fresh breast tissues were measured by Raman spectroscopy. Due to the inherent low sensitivity of Raman spectra, Au@SiO2 shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was utilized to provide supplementary and more informative spectral features. A total of 619 Raman spectra were acquired and compared to 654 SHINERS spectra. The maximum enhancement effect of distinct and specific bands was characterized for different tissue types. When applying the new criteria, excellent separation of FD, DCIS, and IDC was obtained for all tissue types. Most importantly, we were able to distinguish ADH from DCIS. Although only a preliminary distinction was characterized between ADH and NB, the results provided a good foundation of criteria to further discriminate ADH from NB and shed more light toward a better understanding of the mechanism of ADH formation. This is the first report to detect the premalignant (ADH and DCIS) breast tissue frozen sections and also the first report exploiting SHINERS to detect and distinguish breast tissues. The results presented in this study show that SHINERS can be applied to accurately and efficiently identify breast lesions. Further, the spectra can be acquired in a minimally invasive procedure and analyzed rapidly facilitating early and accurate diagnosis in vivo/in situ.}, } @article {pmid24950822, year = {2014}, author = {Trombetta, M and Hall, M and Julian, TB}, title = {Long-term followup of breast preservation by re-excision and balloon brachytherapy after ipsilateral breast tumor recurrence.}, journal = {Brachytherapy}, volume = {13}, number = {5}, pages = {488-492}, doi = {10.1016/j.brachy.2014.05.017}, pmid = {24950822}, issn = {1873-1449}, mesh = {Brachytherapy/adverse effects/instrumentation/*methods ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy/surgery ; Carcinoma, Lobular/*radiotherapy/surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy ; *Mastectomy, Segmental ; Neoplasm Recurrence, Local/*radiotherapy/surgery ; Radiotherapy, Adjuvant ; Reoperation ; Salvage Therapy ; Treatment Outcome ; }, abstract = {PURPOSE: To report our long-term experience with balloon brachytherapy in retreatment of the breast after ipsilateral breast tumor recurrence.

METHODS AND MATERIALS: Between March 2004 and June 2012, 18 patients previously treated with external beam radiotherapy were retreated using either the MammoSite (Hologic Corporation, Marlborough, MA), MammoSite ML (Hologic Corporation), or the Contura (Bard Peripheral Vascular, Inc., Tempe, AZ) brachytherapy devices. Sixteen patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation (11 with infiltrating ductal carcinoma [IDC] and 6 with ductal carcinoma in situ [DCIS]), whereas 2 patients developed an in-field breast cancer likely associated with Hodgkin disease mantle irradiation (27 and 17 years prior, respectively). The recurrent histology of seven was IDC, with seven others recurring as DCIS, three as a combination of IDC/DCIS, and one as infiltrating lobular carcinoma. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy per fraction. Acute and chronic side effects were graded by the Common Terminology Criteria for Adverse Events, version 4.0. Cosmesis was graded by both the Harvard Cosmesis Scale and the Allegheny General Modification of the Harvard Scale.

RESULTS: With a mean of followup of 39.6 months, only 2 patients developed a local recurrence. One patient developed an inflammatory recurrence from what was identified as a moderately differentiated T1N0M0 estrogen receptor-positive recurrence, and the second developed a recurrence immediately adjacent to the implant site. Both patients were treated locally by salvage mastectomy. The patient who developed an inflammatory recurrence rapidly developed visceral metastases including brain lesions and succumbed to her progressive disease. The second patient was successfully salvaged with uncomplicated mastectomy, and she survives to this date. One patient developed a chronic abscess in the sinus tract of the balloon, which required mastectomy, and one developed a post-treatment infection in the catheter tract, which was successfully treated with oral antibiotics. Cosmesis as graded by the Harvard cosmesis criteria and the Allegheny General Modification Score diminished one grade in only 2 patients. All other patients had stable cosmetic scores.

CONCLUSIONS: Use of balloon brachytherapy devices in the treatment of the previously irradiated breast is feasible and may provide adequate local control and acceptable cosmesis in carefully selected patients. Further study and refinement of this therapy is required for more definitive results.}, } @article {pmid24950714, year = {2014}, author = {Aggarwal, A and Al-Rohil, RN and Batra, A and Feustel, PJ and Jones, DM and DiPersio, CM}, title = {Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {459}, pmid = {24950714}, issn = {1471-2407}, support = {R01CA129637/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cyclooxygenase 2/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Integrin alpha3beta1/genetics/*metabolism ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; }, abstract = {BACKGROUND: Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer.

METHODS: Immunohistochemistry was performed to assess co-expression of α3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin α3 subunit or COX2 was scored, and Spearman's rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria.

RESULTS: Although expression of integrin α3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between α3 and COX2 in both tissue microarrays (r(s) = 0.49, p < 0.001, n = 59) and archived samples (r(s) = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage.

CONCLUSIONS: COX2 and α3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin α3β1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of α3β1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target α3β1, and that α3 expression might serve as an independent prognostic biomarker.}, } @article {pmid24948860, year = {2014}, author = {Soni, H and Patel, S and Patel, G and Paranjape, A}, title = {Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats.}, journal = {Journal of Ayurveda and integrative medicine}, volume = {5}, number = {2}, pages = {97-103}, pmid = {24948860}, issn = {0975-9476}, abstract = {BACKGROUND: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties.

OBJECTIVE: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats.

MATERIALS AND METHODS: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg). Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg) along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg) treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by 'analysis of variance' test followed by post hoc Tukey's test, with significant level of P < 0.05.

RESULTS AND DISCUSSION: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group.

CONCLUSION: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property.}, } @article {pmid24944658, year = {2014}, author = {Tamaoki, M and Nio, Y and Tsuboi, K and Nio, M and Tamaoki, M and Maruyama, R}, title = {A rare case of non-invasive ductal carcinoma of the breast coexisting with follicular lymphoma: A case report with a review of the literature.}, journal = {Oncology letters}, volume = {7}, number = {4}, pages = {1001-1006}, pmid = {24944658}, issn = {1792-1074}, abstract = {The double presentation of breast cancer and follicular lymphoma is extremely rare, and only six cases have previously been reported in the literature. In the present study, a case of synchronous ductal carcinoma in situ (DCIS) of the breast and follicular lymphoma is reported. During an annual breast screening procedure, a 49-year-old female presented with a hard induration under the nipple of the right breast and swelling of a soft lymph node (LN) in the right axilla. Mammography and ultrasonography revealed two lesions in the right breast: One was a tumor with microcalcification, 1.0 cm in diameter, and the other was a large, crude calcification, 2.5 cm in diameter. In addition, computed tomography and positron emission tomography revealed swellings of the bilateral axillary (Ax) LN and intra-abdominal para-aortic LN. The patient underwent excisions of the large calcified mass, a micro-calcified tumor and the right AxLN. The pathological and immunohistochemical studies revealed fat necrosis and DCIS of the breast, which was positive for the estrogen receptor and the progesterone receptor, while human epidermal growth factor receptor II protein expression was evaluated as 2+ and stage was classified as pTis pN0 M0, stage 0. Furthermore, the Ax node was diagnosed as follicular lymphoma, which was positive for cluster of differentiation (CD)20, CD79a, CD10 and B-cell lymphoma (Bcl)-2 protein, but negative for Bcl-6 protein. The clinical stage was classified as stage III. The patient was administered chemotherapy followed by radiotherapy to the conserved breast. Two years have passed since the surgery, and the patient is disease-free.}, } @article {pmid24944618, year = {2014}, author = {Zhang, J and Yin, L and Wu, J and Zhang, Y and Xu, T and Ma, R and Cao, H and Tang, J}, title = {Detection of serum VEGF and MMP-9 levels by Luminex multiplexed assays in patients with breast infiltrative ductal carcinoma.}, journal = {Experimental and therapeutic medicine}, volume = {8}, number = {1}, pages = {175-180}, pmid = {24944618}, issn = {1792-0981}, abstract = {The aim of the present study was to assess the effect of the combined detection of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) by Luminex multiplexed assays for the diagnosis, treatment and prognosis of breast cancer. Preoperative levels of serum VEGF and MMP-9 were detected via a lipid chip-based method in 301 breast cancer cases, 83 breast fibroadenoma cases and 40 healthy adults. Postoperative levels of VEGF and MMP-9 were also detected in 118 breast cancer cases. The levels of serum VEGF and MMP-9 in patients with breast infiltrative ductal carcinoma (IDC) were higher than those in the breast fibroadenoma and healthy control groups (P<0.05); there was no statistically significant difference between the breast fibroadenoma and healthy groups (P>0.05). The levels of VEGF and MMP-9 were shown to correlate with the clinical stage, tumor size and the lymph node metastasis status. However, the levels were not associated with age or gender (P>0.05). In addition, the serum level of MMP-9 exhibited a significantly correlation with the VEGF level (r=0.601, P<0.001). Subgroup analysis revealed that in patients with IDC, serum levels of VEGF and MMP-9 prior to surgery were significantly higher than those following surgery (P<0.05). Therefore, the serum levels of VEGF and MMP-9 can be used as markers for the diagnosis of breast IDC and may also be valuable for the prediction of lymph nodes metastasis.}, } @article {pmid24940507, year = {2014}, author = {Sun, SS and Zhang, B and Zhao, HM and Cao, XC}, title = {Association between mammographic features and clinicopathological characteristics in invasive ductal carcinoma of breast cancer.}, journal = {Molecular and clinical oncology}, volume = {2}, number = {4}, pages = {623-629}, pmid = {24940507}, issn = {2049-9450}, abstract = {The aim of the present study was to evaluate the association between mammographic features and clinicopathological characteristics in invasive ductal carcinoma. A total of 231 patients were retrospectively reviewed from January, 2011 to December, 2012. Statistical analysis was performed using Fisher's exact test, χ[2] test, Spearman's correlation and logistic regression, as appropriate. Of the 231 patients who underwent mammography, malignant calcifications were significantly more frequent in carcinomas that were human epidermal growth factor receptor 2 (HER2)-positive (P=0.001) or had a >2 cm size tumor (P=0.006). The pleomorphic-type was correlated with a p53-positive status (P=0.039) or lymph node metastasis (P=0.048), whereas the indistinct amorphous-type was associated with a HER2-positive status (P=0.026). An evident mass was frequently observed in higher Ki-67 expression-level tumors (P=0.002). In conclusion, the aforementioned correlations are noteworthy as they potentially reflect tumor attributes and may serve as a guide for treatment.}, } @article {pmid24937677, year = {2014}, author = {Engels, CC and Fontein, DB and Kuppen, PJ and de Kruijf, EM and Smit, VT and Nortier, JW and Liefers, GJ and van de Velde, CJ and Bastiaannet, E}, title = {Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.}, journal = {British journal of cancer}, volume = {111}, number = {3}, pages = {532-538}, pmid = {24937677}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Carcinoma, Lobular/*immunology/pathology ; Caspase 3/metabolism ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {BACKGROUND: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.

METHODS: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.

RESULTS: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.

CONCLUSIONS: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.}, } @article {pmid24937604, year = {2014}, author = {Chatfield, KC and Sparagna, GC and Sucharov, CC and Miyamoto, SD and Grudis, JE and Sobus, RD and Hijmans, J and Stauffer, BL}, title = {Dysregulation of cardiolipin biosynthesis in pediatric heart failure.}, journal = {Journal of molecular and cellular cardiology}, volume = {74}, number = {}, pages = {251-259}, pmid = {24937604}, issn = {1095-8584}, support = {R01 HL107715/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01HL107715/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Cardiolipins/*biosynthesis/chemistry ; Cardiomyopathy, Dilated/*metabolism/pathology/surgery ; Child ; Child, Preschool ; Female ; Gene Expression ; Heart Failure/*metabolism/pathology/surgery ; Heart Transplantation ; Heart Ventricles/*metabolism/pathology ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mitochondria, Heart/*metabolism/pathology ; Mitochondrial Proteins/genetics/metabolism ; Myocardium/*metabolism/pathology ; }, abstract = {Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC). A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)4CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up- and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart. Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.}, } @article {pmid24936506, year = {2014}, author = {Park, SH and Kim, MJ and Kim, SJ and Kim, EK}, title = {Ductal carcinoma in situ diagnosed using an ultrasound-guided 14-gauge core needle biopsy of breast masses: can underestimation be predicted preoperatively?.}, journal = {Ultrasonography (Seoul, Korea)}, volume = {33}, number = {2}, pages = {128-135}, pmid = {24936506}, issn = {2288-5919}, abstract = {PURPOSE: This study was designed to determine the rate of ductal carcinoma in situ (DCIS)underestimation diagnosed after an ultrasound-guided 14-gauge core needle biopsy (US-14G-CNB) of breast masses and to compare the clinical and imaging characteristics between trueDCIS and underestimated DCIS identified following surgical excision.

METHODS: Among 3,124 US-14G-CNBs performed for breast masses, 69 lesions in 60 patients were pathologically-determined to be pure DCIS. We classified these patients according to the final pathology after surgical excision as those with invasive ductal carcinoma (underestimated group) and those with DCIS (non-underestimated group). We retrospectively reviewed and compared the clinical and imaging characteristics between the two groups.

RESULTS: Of the 69 lesions, 21 were shown after surgery to be invasive carcinomas; the rateof DCIS underestimation was 30.4%. There were no statistically significant differences withrespect to the clinical symptoms, age, lesion size, mammographic findings, and ultrasonographic findings except for the presence of abnormal axillary lymph nodes as detected on ultrasound. The lesions in 2 patients in the non-underestimated group (2/41, 4.9%) and 5 patients in the underestimated group (5/19, 26.3%) were associated with abnormal lymph nodes on axillary ultrasound, and the presence of abnormal axillary lymph nodes on ultrasound was tatistically significant (P=0.016).

CONCLUSION: We found a 30.4% rate of DCIS underestimation in breast masses based on a US-14G-CNB. The presence of abnormal lymph nodes as detected on axillary ultrasound may be useful to preoperatively predict underestimation.}, } @article {pmid24936496, year = {2014}, author = {Myong, JH and Choi, BG and Kim, SH and Kang, BJ and Lee, A and Song, BJ}, title = {Imaging features of complex sclerosing lesions of the breast.}, journal = {Ultrasonography (Seoul, Korea)}, volume = {33}, number = {1}, pages = {58-64}, pmid = {24936496}, issn = {2288-5919}, abstract = {PURPOSE: The purpose of this study was to evaluate the imaging features of complex sclerosing lesions of the breast and to assess the rate of upgrade to breast cancer.

METHODS: From March 2008 to May 2012, seven lesions were confirmed as complex sclerosing lesions by ultrasonography-guided core needle biopsy. Final results by either surgical excision or follow-up imaging studies were reviewed to assess the rate of upgrade to breast cancer. Two radiologists retrospectively analyzed the imaging findings according to the Breast Imaging Reporting and Data System classification.

RESULTS: Five lesions underwent subsequent surgical excision and two of them revealed ductal carcinoma in situ (n=1) and invasive ductal carcinoma (n=1). Our study showed a breast cancer upgrade rate of 28.6% (2 of 7 lesions). Two lesions were stable on imaging follow-up beyond 1 year. The mammographic features included masses (n=4, 57.1%), architectural distortion (n=2, 28.6%), and focal asymmetry (n=1, 14.3%). Common B-mode ultrasonographic features were irregular shape (n=6, 85.7%), spiculated margin (n=5, 71.4 %), and hypoechogenicity (n=7, 100%). The final assessment categories were category 4 (n=6, 85.7%) and category 5 (n=1, 14.3%).

CONCLUSION: The complex sclerosing lesions were commonly mass-like on mammography and showed the suspicious ultrasonographic features of category 4. Due to a high underestimation rate, all complex sclerosing lesions by core needle biopsy should be excised.}, } @article {pmid24936222, year = {2014}, author = {Song, D and Cui, M and Zhao, G and Fan, Z and Nolan, K and Yang, Y and Lee, P and Ye, F and Zhang, DY}, title = {Pathway-based analysis of breast cancer.}, journal = {American journal of translational research}, volume = {6}, number = {3}, pages = {302-311}, pmid = {24936222}, issn = {1943-8141}, abstract = {INTRODUCTION: Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer.

METHODS: 13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 131 cancer pathway-related proteins and phosphoproteins in 33 paired breast cancers were measured using our innovative Protein Pathway Array.

RESULTS: Out of 1,243 mRNAs, 68.7% (854) were detected in breast cancer and 395 mRNAs were statistically significant (fold change >2) between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 131 proteins and phosphoproteins, 68% (89) were detected in cancer tissues and 57 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decreases in both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) were differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more than 15 pathways were altered in breast cancer and 6 of which were shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT pathways.

CONCLUSIONS: There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting different regulation mechanisms between proteins and mRNAs.}, } @article {pmid24936218, year = {2014}, author = {Wang, F and Hou, J and Shen, Q and Yue, Y and Xie, F and Wang, X and Jin, H}, title = {Mouse mammary tumor virus-like virus infection and the risk of human breast cancer: a meta-analysis.}, journal = {American journal of translational research}, volume = {6}, number = {3}, pages = {248-266}, pmid = {24936218}, issn = {1943-8141}, abstract = {Despite a large number of molecular epidemiological studies, the association of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) infection with the risk of human breast cancer remains inconclusive mainly due to the heterogeneity in populations involved. We performed a systematic search of multiple bibliographic databases, up to October 2013, to identify all studies on detection of MMTV-LV DNA in human breast cancer using polymerase chain reaction (PCR) and conducted the first comprehensive meta-analysis of published literature to explore the relevance of MMTV-LV to human breast cancer. As a result, meta-analysis of twelve case-control studies identified from the systematic search revealed a significantly increased risk for breast cancer development after MMTV-LV infection (OR=15.20; 95% CI: 9.98-23.13). However, there was no significant correlation between MMTV-LV infection and the transformation from ductal carcinoma in situ to invasive ductal carcinoma (OR=1.16; 95% CI: 0.27-4.97). In addition, MMTV-LV infection was not associated with the expression of estrogen receptor (ER) (OR=0.89; 95% CI: 0.48-1.65), progesterone receptor (PR) (OR=0.73; 95% CI: 0.22-2.42), HER-2 (OR=0.65; 95% CI: 0.30-1.43) or p53 (OR=1.47; 95% CI: 0.79-2.73). Finally, we found that the prevalence of MMTV-LV in breast carcinoma was significantly higher in patients from Western countries (prevalence=40.4%, 95% CI: 28.9%-51.9%) than in Asian patients (prevalence: 8.5%; 95% CI: -7.1%-24.1%) in a subgroup and meta-regression analysis (p=0.015). In summary, the meta-analysis of published studies revealed a significantly increased risk for breast cancer development after MMTV-LV infection. In addition, the prevalence of MMTV-LV is much higher in breast cancer patients from Western countries than Asian patients.}, } @article {pmid24936147, year = {2014}, author = {Vormbrock, J and Liebeton, J and Wirdeier, S and Meissner, A and Butz, T and Trappe, HJ and Plehn, G}, title = {Determinants of right ventricular muscle mass in idiopathic dilated cardiomyopathy: impact of left ventricular muscle mass and pulmonary hypertension.}, journal = {International journal of medical sciences}, volume = {11}, number = {8}, pages = {834-840}, pmid = {24936147}, issn = {1449-1907}, mesh = {Adult ; Aged ; Cardiac Catheterization/methods ; Cardiomyopathy, Dilated/diagnostic imaging/*pathology ; Female ; Heart Ventricles/diagnostic imaging/*physiopathology ; Hemodynamics ; Humans ; Hypertension, Pulmonary/diagnostic imaging/*physiopathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscles/diagnostic imaging/pathology ; Radiography ; }, abstract = {INTRODUCTION: Although chronic pulmonary hypertension and right ventricular (RV) function carry important functional and prognostic implications in idiopathic dilated cardiomyopathy (IDC), little information on RV muscle mass (RVMM) and its determinants has been published.

METHODS: Our study comprised thirty-five consecutive patients with IDC, left ventricular (LV) ejection fraction<40% and NYHA class≥2. Hemodynamic data and parameters on LV and RV geometry were derived from right heart catheterisation and cardiac magnetic resonance imaging.

RESULTS: RVMM was normalized to body size using a common linear, body surface area based approach (RVMMI) and by an allometric index (RVMM-AI) incorporating adjustment for age, height and weight. Stepwise multiple regression analysis revealed that pulmonary artery pressure and left ventricular muscle mass were independent predictors of RVMM-AI. The interventricular mass ratio of RV and LV mass (IVRM) was closely related to RVMM (r=0.79, p<0.001) and total muscle mass (r=0.39, p<0.02). However, there was no significant relationship between LVMM and IVMR (r=0.17, p=0.32).

CONCLUSION: Our data suggest that an increase in RV mass in IDC may be explained by two mechanisms: First, as a consequence of the myopathic process itself resulting in a balanced hypertrophy of both ventricles. Second, due to the chamber specific burden of pulmonary artery pressure rise, resulting in unbalanced RV hypertrophy.}, } @article {pmid24932904, year = {2014}, author = {Min, KW and Park, HK and Kim, WY and Kim, WS and Lim, SD and Han, HS and Hwang, TS}, title = {Primary ductal adenocarcinoma of the lacrimal gland, associated with abundant intracytoplasmic lumens containing some eosinophilic hyaline globules: cytological, histological and ultrastructural findings.}, journal = {Ultrastructural pathology}, volume = {38}, number = {5}, pages = {363-366}, doi = {10.3109/01913123.2014.921656}, pmid = {24932904}, issn = {1521-0758}, mesh = {Adenocarcinoma/metabolism/*ultrastructure ; Carcinoma, Squamous Cell/diagnosis/*ultrastructure ; Head and Neck Neoplasms/diagnosis/*ultrastructure ; Humans ; Hyalin/*ultrastructure ; Immunohistochemistry/methods ; Lacrimal Apparatus/*ultrastructure ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial/*ultrastructure ; Salivary Gland Neoplasms/diagnosis/metabolism/ultrastructure ; Squamous Cell Carcinoma of Head and Neck ; }, abstract = {A primary ductal adenocarcinoma (PDA) of the lacrimal gland is a rare distinct subtype of an epithelial tumor arising in the lacrimal gland. PDA is the counterpart of salivary duct carcinoma (SDC) resembling an invasive ductal carcinoma (IDC) of the breast. In our case, PDA revealed histopathological and immunohistochemical results corresponding to SDC. Interestingly, the tumor cells showed intracytoplasmic vacuoles containing dense eosinophilic hyaline globules at light microscopy. Ultrastructurally, the tumor cells exhibited microvilli-lined intracytoplasmic lumen containing homogenous electron-dense secretory products. A previous study demonstrated that numerous intracytoplasmic lumens of tumor cells are favored breast malignant tumor, similar to the histopathology of PDA, rather than benign lesion. This characteristic finding may be meaningful to diagnose high grade epithelial tumors including PDA.}, } @article {pmid24932848, year = {2014}, author = {Chang, YC and Huang, YS and Huang, CS and Chen, JH and Chang, RF}, title = {Intrinsic subtypes and tumor grades in breast cancer are associated with distinct 3-D power Doppler sonographic vascular features.}, journal = {European journal of radiology}, volume = {83}, number = {8}, pages = {1368-1374}, doi = {10.1016/j.ejrad.2014.05.005}, pmid = {24932848}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Carcinoma, Lobular/diagnostic imaging/pathology ; Female ; Humans ; *Imaging, Three-Dimensional ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Retrospective Studies ; *Ultrasonography, Doppler ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: This study aimed to investigate the three-dimensional (3-D) power Doppler ultrasonographic (PDUS) vascular features of breast carcinoma according to intrinsic subtypes, nodal stage, and tumor grade.

MATERIALS AND METHODS: Total 115 receiving mastectomy breast carcinomas (mean size, 2.5 cm; range, 0.7-6.5 cm), including 102 invasive ductal carcinomas (IDC), 10 ductal carcinomas in situ (DCIS), and 3 invasive lobular carcinomas (ILC) diagnosed after mastectomy, were used in this retrospective study. Sixty IDC had nodal status and histopathologic tumor grades available for analysis. Vascular features, including number of vascular trees (NV), longest path length (LPL), total vessel length (TVL), number of bifurcations (NB), distance metric (DM), inflection count metric (ICM), vessel diameter (VD), and vessel-to-volume ratio (VVR) were extracted using 3-D thinning method. The Mann-Whitney U test, Student's t-test, one-way ANOVA, and Kruskal-Wallis test were performed as appropriate.

RESULTS: There was no significant difference of vascular features among IDC, DCIS and ILC. Except VD, vascular features in luminal type were significantly lower compared to HER2-enriched or triple negative types (p<0.05). Compared to ER+ (estrogen receptor positive) tumors, all features in ER- (estrogen receptor negative) tumors were significantly higher (p<0.01). Despite some significantly higher vascular features in high grade IDC compared to low and intermediate grade, there was no significant correlation between vascular features and nodal stages.

CONCLUSION: Differences in 3-D PDUS vascular features among intrinsic types of IDC are attributed to their ER status. Vascular features extracted by 3-D PDUS correlate with tumor grades but not nodal stage in IDC.}, } @article {pmid24932298, year = {2014}, author = {Patel, AS and Allen, JE and Dicker, DT and Sheehan, JM and Glantz, MJ and El-Deiry, WS}, title = {Detection of circulating tumor cells in the cerebrospinal fluid of a patient with a solitary metastasis from breast cancer: A case report.}, journal = {Oncology letters}, volume = {7}, number = {6}, pages = {2110-2112}, pmid = {24932298}, issn = {1792-1074}, abstract = {Brain lesions identified following the diagnosis and eradication of primary cancers are often ambiguous in origin, existing as a solitary metastasis or an independent primary brain tumor. The brain is a relatively common site of metastasis with breast cancer, although determining whether metastases have originated from the breast or brain is often not possible without invasive biopsies. In the current case report, a patient presented with a brain lesion identified by radiography and was without systemic disease. The patient had previously exhibited a complete response to chemotherapy and surgery for a poorly differentiated invasive ductal carcinoma. The origin of the brain lesion could not be determined by magnetic resonance imaging, giving rise to a diagnostic dilemma with diverging treatment options. We previously reported a method to isolate and enumerate tumor cells of epithelial origin in the cerebrospinal fluid (CSF). CSF tumor cell analysis of the patient revealed massive CSF tumor cell burden of epithelial origin, indicating that the brain lesion was likely of breast origin. The current case report highlights the use of CSF tumor cell detection as a differential diagnostic tool, in addition to its previously demonstrated use as a marker of disease burden and therapeutic response.}, } @article {pmid24931343, year = {2014}, author = {Oda, Y and Aishima, S and Morimatsu, K and Shindo, K and Fujino, M and Mizuuchi, Y and Hattori, M and Miyazaki, T and Tanaka, M and Oda, Y}, title = {Pancreatic intraepithelial neoplasia in the background of invasive ductal carcinoma of the pancreas as a prognostic factor.}, journal = {Histopathology}, volume = {65}, number = {3}, pages = {389-397}, doi = {10.1111/his.12397}, pmid = {24931343}, issn = {1365-2559}, mesh = {Aged ; Atrophy ; Carcinoma in Situ/*pathology ; Carcinoma, Pancreatic Ductal/*pathology/secondary ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Pancreatic Neoplasms/*pathology ; Prognosis ; }, abstract = {AIMS: Of the recognized precursor lesions of pancreatic adenocarcinoma, pancreatic intraepithelial neoplasia (PanIN) is the most common form. However, little is known about the relationship between the grade of PanIN and prognosis for patients with invasive ductal carcinoma.

METHODS AND RESULTS: In 124 patients with invasive ductal carcinoma, we examined the grade and number of PanIN lesions in all slides of resected pancreas. The prevalence rates of PanIN-1A, PanIN-1B, PanIN-2 and PanIN-3 were 86%, 84%, 57% and 30%, respectively. We allocated PanIN-2 and PanIN-3 cases into a PanIN-high group, and cases showing PanIN-1A, PanIN-1B or absence of PanIN into a PanIN-low group. In clinicopathological analysis, PanIN-high status was significantly correlated with the number of PanIN lesions (P < 0.0001). Disease-free and overall survival were statistically better in the PanIN-high group than in the PanIN-low group (P = 0.0005 and P = 0.0003). Univariate and multivariate analyses revealed that tumour size and PanIN-low status were statistically significant factors for a poorer prognosis (P = 0.042 and P = 0.007).

CONCLUSIONS: In a pathological examination, it is important to evaluate the grade and number of PanINs in assessing the prognosis of pancreatic cancer.}, } @article {pmid24929470, year = {2014}, author = {Lieshout, Pv and Ben-David, B and Lipski, M and Namasivayam, A}, title = {The impact of threat and cognitive stress on speech motor control in people who stutter.}, journal = {Journal of fluency disorders}, volume = {40}, number = {}, pages = {93-109}, doi = {10.1016/j.jfludis.2014.02.003}, pmid = {24929470}, issn = {1873-801X}, mesh = {Adult ; Anxiety/physiopathology ; Case-Control Studies ; Cognition/physiology ; Female ; Humans ; Language ; Lip/physiopathology ; Male ; Middle Aged ; *Motor Skills ; Phonetics ; Psychomotor Performance ; Reaction Time ; Speech/*physiology ; Speech Acoustics ; Speech Production Measurement/methods ; Stress, Psychological/*physiopathology ; Stroop Test ; Stuttering/physiopathology/*psychology ; Time Factors ; Young Adult ; }, abstract = {PURPOSE: In the present study, an Emotional Stroop and Classical Stroop task were used to separate the effect of threat content and cognitive stress from the phonetic features of words on motor preparation and execution processes.

METHOD: A group of 10 people who stutter (PWS) and 10 matched people who do not stutter (PNS) repeated colour names for threat content words and neutral words, as well as for traditional Stroop stimuli. Data collection included speech acoustics and movement data from upper lip and lower lip using 3D EMA.

RESULTS: PWS in both tasks were slower to respond and showed smaller upper lip movement ranges than PNS. For the Emotional Stroop task only, PWS were found to show larger inter-lip phase differences compared to PNS. General threat words were executed with faster lower lip movements (larger range and shorter duration) in both groups, but only PWS showed a change in upper lip movements. For stutter specific threat words, both groups showed a more variable lip coordination pattern, but only PWS showed a delay in reaction time compared to neutral words. Individual stuttered words showed no effects. Both groups showed a classical Stroop interference effect in reaction time but no changes in motor variables.

CONCLUSION: This study shows differential motor responses in PWS compared to controls for specific threat words. Cognitive stress was not found to affect stuttering individuals differently than controls or that its impact spreads to motor execution processes.

EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to: (1) discuss the importance of understanding how threat content influences speech motor control in people who stutter and non-stuttering speakers; (2) discuss the need to use tasks like the Emotional Stroop and Regular Stroop to separate phonetic (word-bound) based impact on fluency from other factors in people who stutter; and (3) describe the role of anxiety and cognitive stress on speech motor processes.}, } @article {pmid24921921, year = {2014}, author = {Chen, AC and Paulino, AC and Schwartz, MR and Rodriguez, AA and Bass, BL and Chang, JC and Teh, BS}, title = {Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {111}, number = {3}, pages = {619-622}, pmid = {24921921}, issn = {1532-1827}, mesh = {Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Carcinoma, Papillary/mortality/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Tumor Burden ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC).

METHODS: Retrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End RESULTS database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC.

RESULTS: A higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types.

CONCLUSIONS: Despite IMPC's higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.}, } @article {pmid24919244, year = {2014}, author = {So, K and Habashy, D and Doyle, B and Chan, L}, title = {Indwelling urinary catheters: pattern of use in a public tertiary-level Australian hospital.}, journal = {Urologic nursing}, volume = {34}, number = {2}, pages = {69-73}, pmid = {24919244}, issn = {1053-816X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Australia ; Catheter-Related Infections/*etiology/nursing ; Female ; Hospitals, Public ; Humans ; Male ; Middle Aged ; Nursing Audit ; Tertiary Care Centers ; Urinary Catheterization/*adverse effects/nursing/*statistics & numerical data ; Urinary Catheters/*adverse effects ; }, abstract = {An audit of charts from patients identified as having an indwelling urinary catheter (IDC) was conducted in a 450-bed, tertiary level hospital (Concord Repatriation General Hospital) in Australia. Documentation of relevant information regarding IDC in the medical record included indication for catheterization, insertion and removal dates, use of antibiotics, place of insertion, designation of inserter, catheter type, availability of IDC kits, and use of catheter fixation devices.}, } @article {pmid24917206, year = {2014}, author = {Kurbel, S and Marjanović, K and Dmitrović, B}, title = {A model of immunohistochemical differences between invasive breast cancers and DCIS lesions tested on a consecutive case series of 1248 patients.}, journal = {Theoretical biology & medical modelling}, volume = {11}, number = {}, pages = {29}, pmid = {24917206}, issn = {1742-4682}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Models, Biological ; *Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: A previous theoretic model (Tumour Biol 2013;34:1-7.) that breast tumor types differ in the relative rate of tissue invasion was elaborated and developed on a consecutive case series.

METHOD: Histologic data of 68 ductal breast cancer in situ (DCIS) and 1180 invasive ductal cancer (IDC) patients were collected and analyzed.

RESULTS: ER+PgR- phenotype was more common in Luminal B2 than among the pooled Luminal A&B1 (p = 0.0002), and more frequent in Luminal B1 than in Luminal A (p = 0.0167). The same phenotype was associated with the age older than 54 years in Luminal B1 and in B2 patients. HER2 type cancers were more frequent in older patients (p = 0.0038).Tumor progression from DCIS to IDC was found 39% faster than the average in Luminal B1 tumors, supporting the clinical importance of this tumor type. A rare combination of low Ki-67 in HER2 type cancers (only 14% of HER2 type cancers) showed very slow transition to IDC (occurring at only 53.55% of average progression rate), while triple-negative cancers progressed faster than the average, despite Ki-67 value (104.63% for low and 114.27% for high Ki-67 tumors).In three tumor types with positive steroid receptors the ER+PgR- phenotype showed slower IDC transition than the ER+PgR+ phenotype of the same tumor type (difference in progression rate was 38% for Luminal A, 46% for Luminal B1 and 67% for Luminal B2 with Ki67 > 14%).Triple-negative tumors in younger patients exceeded the expected average progression rate by 24%, while in HER2 type tumors, the rate of tissue invasion was in younger patients 20% lower than the expected value.

CONCLUSIONS: The relative rate of tissue invasion differed substantialy among our patients. Differences depended on tumor types, steroid expression phenotypes and age. The dysfunctional ERs in the ER+PgR- phenotype showed slower rates of tissue invasion, suggesting that ligand binding to functional breast tumor ERs, beside promoting the PgR expression, possibly also promotes tumor transition to the invasive phase.In triple-negative tumors, an age dependent premenopausal mechanism possibly acted as an accelerator of tissue invasion, while faster tissue invasion by HER2-overexpressed tumors in older patients possibly depended on an unidentified mechanism that takes more time to be acquired, so it was less present in premenopausal patients.}, } @article {pmid24913934, year = {2014}, author = {Alsharif, S and Daghistani, R and Kamberoğlu, EA and Omeroglu, A and Meterissian, S and Mesurolle, B}, title = {Mammographic, sonographic and MR imaging features of invasive micropapillary breast cancer.}, journal = {European journal of radiology}, volume = {83}, number = {8}, pages = {1375-1380}, doi = {10.1016/j.ejrad.2014.05.003}, pmid = {24913934}, issn = {1872-7727}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Papillary/*diagnosis/diagnostic imaging/pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Interpretation, Computer-Assisted ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: Describe mammographic, sonographic and MRI findings of invasive micropapillary carcinoma (IMPC) of the breast.

MATERIALS AND METHODS: Review of the pathology database identified 43 patients (mean age, 59.3 years) with the diagnosis of breast IMPC. Three patients had no available imaging studies. Mammograms (40), breast ultrasounds (33) and MRIs (8) were retrospectively evaluated by two radiologists in consensus following the BI-RADS Lexicon. Clinical, histopathologic features, as well as hormone status were recorded.

RESULTS: Twenty patients presented with palpable abnormality (20/40, 50%). Thirty-five patients had an abnormal mammogram (87.5%, 35/40) showing 39 lesions, 29 corresponding to masses (29/39, 74.4%), 11 associated with microcalcifications and two associated with architectural distortion. Sonography identified 41 masses (in 33 patients) displaying an irregular shape (30/41, 73.2%), appearing hypoechoic (39/41, 95%), with spiculated or angular margins (26/41, 63.4%), non-parallel orientation (26/41, 63.4%) and combined acoustic posterior pattern (18/41, 44%). MRI identified 13 lesions (in eight patients), 12 as masses (12/13, 92.3%) with irregular or spiculated margins (12/12, 100%), eight displaying an irregular or lobulated shape (8/12, 66.7%), six with homogeneous internal enhancement (6/12, 50%) and eight with type 3 enhancement curve (8/12, 61.5%). Associated non-mass like enhancement was noted in two patients. Twenty-nine patients had associated lymphovascular invasion (29/40, 72.5%) and axillary lymph node metastases were present in 22 of the 39 patients (22/39, 56%).

CONCLUSION: Invasive ductal carcinoma with IMPC features display imaging findings highly suspicious of malignant lesions. They are associated with high lymphovascular invasion and lymph node metastases rates.}, } @article {pmid24912071, year = {2014}, author = {Dixon, ML and Fox, KC and Christoff, K}, title = {A framework for understanding the relationship between externally and internally directed cognition.}, journal = {Neuropsychologia}, volume = {62}, number = {}, pages = {321-330}, doi = {10.1016/j.neuropsychologia.2014.05.024}, pmid = {24912071}, issn = {1873-3514}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Attention/physiology ; *Brain Mapping ; Cognition/*physiology ; Humans ; *Intention ; *Internal-External Control ; Nerve Net/physiology ; Neural Pathways/physiology ; Prefrontal Cortex/*physiology ; }, abstract = {Externally directed cognition (EDC) involves attending to stimuli in the external environment, whereas internally directed cognition (IDC) involves attending internally to thoughts, memories and mental imagery. To date, most studies have focused on the competition or trade-offs between these modes of cognition. However, both EDC and IDC include a variety of cognitive states that differ along multiple dimensions. These dimensions may influence the way in which EDC and IDC relate to each other. In this review, we present a novel framework that considers whether cognitive resources are oriented externally or internally, and also whether a given cognitive state involves intentional (i.e., voluntary) or spontaneous (i.e., involuntary) processing. Within this framework, we examine the conditions under which EDC and IDC are expected to either compete, or co-occur without interference. We argue that EDC and IDC are not inherently antagonistic, but when both involve higher levels of intentionality they are increasingly likely to compete, due to the capacity limitations of intentional processing. In contrast, if one or both involve spontaneous processing, EDC and IDC can co-occur with minimal interference given that involuntary processes are not subject to the same capacity constraints. A review of the brain regions implicated in EDC and IDC suggests that their neural substrates are partially segregated and partially convergent. Both EDC and IDC recruit the lateral prefrontal cortex (PFC) during intentional processing, and may therefore compete over the processes and representational space it supports. However, at lower levels of intentionality, EDC and IDC rely on largely distinct neural structures, which may enable their co-occurrence without interference. The proposal that EDC and IDC can in some cases co-occur, provides a framework for understanding the complex mental states that underlie theory of mind, creativity, the influence of self-evaluative processing on cognitive control, and memory-guided attention.}, } @article {pmid24909183, year = {2014}, author = {Min, KW and Kim, DH and Do, SI and Kim, K and Lee, HJ and Chae, SW and Sohn, JH and Pyo, JS and Oh, YH and Kim, WS and Lee, SY and Oh, S and Choi, SH and Park, YL and Park, CH}, title = {Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {12}, pages = {1196-1206}, doi = {10.1111/apm.12285}, pmid = {24909183}, issn = {1600-0463}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/*genetics/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2/genetics/*metabolism ; Matrix Metalloproteinase 9/genetics/*metabolism ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {Matrix metalloproteinases (MMPs) are matrix-degrading enzymes that play a pivotal role in aggressive behaviours, such as rapid tumour growth, invasion, and metastasis, of several types of solid tumours. In particular, stromal MMP-2 plays important roles in the progression of malignant tumours, but most clinical studies have focused on tumoural MMP-2 and -9 expression, and not stromal MMP-2 expression. One hundred and seventy-seven cases diagnosed as invasive ductal carcinoma of the breast between 2000 and 2005 were included in this study. Expressions of tumoural MMP-2 and -9 and stromal MMP-2 were analysed by immunostaining on a tissue microarray. Subsequently, the associations between those results and various clinicopathological parameters were evaluated. Stromal MMP-2 expression correlated significantly with clinicopathological parameters such as advanced T category, larger tumour size, high histological grade, tumour necrosis, ER- and PR-negative, and HER-2-positive (all p < 0.05). In univariate and multivariate analyses, overall survival was linked with stromal MMP-2 expression as well as dual expression of stromal MMP-2 and tumoural MMP-2 and -9 (all p < 0.05). Stromal MMP-2 expression may play a crucial role in predicting aggressive clinical behaviour in breast cancer patients.}, } @article {pmid24903281, year = {2014}, author = {Doron, G and Mizrahi, M and Szepsenwol, O and Derby, D}, title = {Right or flawed: relationship obsessions and sexual satisfaction.}, journal = {The journal of sexual medicine}, volume = {11}, number = {9}, pages = {2218-2224}, doi = {10.1111/jsm.12616}, pmid = {24903281}, issn = {1743-6109}, mesh = {Adult ; Depression ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Obsessive-Compulsive Disorder/*psychology ; *Personal Satisfaction ; *Sexual Partners ; Young Adult ; }, abstract = {INTRODUCTION: Relationship obsessive-compulsive disorder (ROCD) is marked by the presence of obsessions and compulsions focusing on romantic relationships. ROCD symptoms were previously linked with decreased relationship quality and might interfere with sexual functioning.

AIM: The study aims to examine the association between ROCD symptoms and sexual satisfaction.

METHODS: Participants completed an online survey assessing ROCD symptoms and relationship and sexual satisfaction levels. Depression, general worry, obsessive-compulsive disorder (OCD) symptoms, and attachment orientation were also measured.

MAIN OUTCOME MEASURE: The main outcome measures were self reported relationship satisfaction and sexual satisfaction.

RESULTS: ROCD symptoms were associated with decreased sexual satisfaction over and above symptoms of depression, general worry, OCD, and attachment orientation. The link between ROCD symptoms and sexual satisfaction was mediated by relationship satisfaction.

CONCLUSIONS: Identifying and addressing ROCD symptoms may be important for treatment of sexual functioning.}, } @article {pmid24897776, year = {2014}, author = {Nedved, D and Connor, C and Sharma, P and O'Neil, M}, title = {Collision tumour of the breast composed of Merkel cell carcinoma and invasive ductal carcinoma: a case report.}, journal = {Pathologica}, volume = {106}, number = {1}, pages = {16-21}, pmid = {24897776}, issn = {0031-2983}, mesh = {Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Merkel Cell/diagnosis/*pathology/surgery ; Carcinoma, Neuroendocrine/diagnosis/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; }, abstract = {We report a case of a 71-year-old female with a palpable breast mass. Pathologic evaluation of the breast mass showed a unique collision tumour with a high-grade invasive and in-situ ductal carcinoma component and a high-grade neuroendocrine carcinoma component. The neuroendocrine component turned out to be Merkel cell carcinoma (MCC), with immunohistochemical confirmation. To the best of our knowledge, this is the first case report of a collision tumour with ordinary ductal carcinoma and MCC in the breast.}, } @article {pmid24897222, year = {2014}, author = {de Oliveira, DR and Carvalho, ES and Campos, LC and Leal, JA and Sampaio, EV and Cassali, GD}, title = {[Nutritional status of patients with breast cancer attended in the Mastology Service of Belo Horizonte's Hospital das Clínicas in the state of Minas Gerais, Brazil].}, journal = {Ciencia & saude coletiva}, volume = {19}, number = {5}, pages = {1573-1580}, doi = {10.1590/1413-81232014195.02262013}, pmid = {24897222}, issn = {1678-4561}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Body Composition ; Brazil ; Breast Neoplasms/pathology/*physiopathology ; Cross-Sectional Studies ; Female ; Hospitals ; Humans ; Middle Aged ; *Nutritional Status ; }, abstract = {The scope of this article is to evaluate the nutritional status, body composition and tumor characteristics of 31 patients with breast cancer attended at the Mastology Service of Hospital das Clínicas of the Federal University of Minas Gerais. Dietary data were obtained from the 24-hour dietary recall in the pre-operative state and analyzed by the DietWin Professional 2008 Nutrition Software. Body composition was assessed by bioelectrical impedance analysis. The tumor characterization data were collected from medical records. The mean age of patients was 50.75 ± 14.34 years. Excess body weight was found in 58% and waist circumference greater than 80 cm in 64.5% of patients Excessive consumption of oils and sugars was observed in 90.3% and 83.8%, respectively. Most had low intakes of calcium and vitamins B6, B12 and A. The predominant diagnosis was type II histological grade invasive ductal carcinoma in stage II or III. The prevalence of overweight and inadequate dietary intake demonstrate the need for individualized nutritional guidance and monitoring to improve the prognosis and quality of the life of patients.}, } @article {pmid24894697, year = {2014}, author = {Nadrljanski, M and Maksimović, R and Plešinac-Karapandžić, V and Nikitović, M and Marković-Vasiljković, B and Milošević, Z}, title = {Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: ductal carcinoma in situ vs. invasive ductal carcinoma.}, journal = {European journal of radiology}, volume = {83}, number = {8}, pages = {1363-1367}, doi = {10.1016/j.ejrad.2014.05.006}, pmid = {24894697}, issn = {1872-7727}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Prospective Studies ; }, abstract = {OBJECTIVES: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS.

MATERIALS AND METHODS: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n=30) and IDC (n=30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC.

RESULTS: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p<0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p<0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p<0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p<0.0001).

CONCLUSIONS: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.}, } @article {pmid24894013, year = {2014}, author = {Das, U and Lakshmaiah, KC and Govind Babu, K and Suresh, TM and Lokanatha, D and Jacob, L and Babu, S}, title = {The actual scenario of neoadjuvant chemotherapy of breast cancer in developing country: a report of 80 cases of breast cancer from a tertiary cancer center in India.}, journal = {Journal of cancer research and clinical oncology}, volume = {140}, number = {10}, pages = {1777-1782}, pmid = {24894013}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/economics/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/*drug therapy/secondary/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; India/epidemiology ; Induction Chemotherapy ; Lymphatic Metastasis ; Medical Records ; Middle Aged ; Molecular Targeted Therapy/*economics ; Neoadjuvant Therapy/*methods ; Neoplasm Staging ; Postmenopause ; Premenopause ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Rural Population/statistics & numerical data ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {BACKGROUND: Preoperative or neoadjuvant chemotherapy is an option in patients with large operable breast cancer to facilitate the breast conservation and to downstage the disease to make inoperable breast cancer to operable one. It is also called the window of opportunity; it provides a unique opportunity to derive biological information related to tumor response. Neoadjuvant chemotherapy has been compared with standard, postoperative adjuvant chemotherapy with goals of improving survival and facilitating local therapies. Unfortunately, neoadjuvant chemotherapy does not seem to improve overall survival. There is a lack of data from India regarding the neoadjuvant chemotherapy. The present study was carried out to assess the response to neoadjuvant chemotherapy in breast cancer.

MATERIALS AND METHODS: We retrospectively analyzed the records of patients who were started on neoadjuvant chemotherapy (NACT) at our center for 1 year (August 2012 to July 2013). Case files were thoroughly reviewed, and patient's characteristics (age, pre-/postmenopausal status, family history of breast/ovarian/other cancer), mode of detection, treatment, and histological features were analyzed.

RESULTS: Out of 322 patients with breast cancer registered in our institute, 80 patients received neoadjuvant chemotherapy. Median age was 45 years. The most common presentation was left-sided breast lump (Lt > Rt) with a median duration of symptoms was 4 months. Postmenopausal patients (53.75 %) were more than premenopausal (46.25 %). Seventy-two patients were stage III and 8 were stage II disease. Bilateral breast cancer was seen in 8 patients. Most common histological type was invasive ductal carcinoma (95 %). Estrogen receptor (ER) and/or progesterone (PR) positive were seen in 47 (58.75 %) patients. Ten patients were HER2 positive and ER/PR negative, and 5 patients were triple positive. Triple-negative patients were 22 (27.5 %). The most common neoadjuvant chemotherapy protocol used was FEC. Clinical response before surgery was CR 13 %, PR 68.68 %, stable disease 11.62 %, and progressive disease 4.65 %. Pathological CR was seen in 6.9 % of tumors. Nodal status at surgery was ypN0-40 %, ypN1-28. 5 %. ypN2-27 %, and ypN3-4.28 %.

CONCLUSION: In a population of predominantly locally advanced patients, NACT with anthracyclines yielded pCR rates comparable to published studies. There were a high proportion of HER2-positive patients, most of whom could not receive anti-HER2 therapy due to financial reasons.}, } @article {pmid24888777, year = {2014}, author = {Tajiri, R and Inokuchi, M and Sawada-Kitamura, S and Kawashima, H and Nakamura, R and Oyama, T and Dobashi, Y and Ooi, A}, title = {Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.}, journal = {Pathology international}, volume = {64}, number = {5}, pages = {231-236}, doi = {10.1111/pin.12158}, pmid = {24888777}, issn = {1440-1827}, mesh = {Adult ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Biopsy, Needle ; Breast/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/therapy ; Carcinoma, Ductal, Breast/*genetics/metabolism/therapy ; Carcinoma, Lobular/*genetics/metabolism/therapy ; Cyclin D1/genetics/metabolism ; DNA Fingerprinting/*methods ; DNA, Neoplasm/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mastectomy ; Multiplex Polymerase Chain Reaction/*methods ; Receptor, ErbB-2/genetics/metabolism ; Treatment Outcome ; }, abstract = {A needle biopsy of a mass in the right breast of a 36-year-old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E-cadherin-negative invasive lobular carcinoma (ILC), and the rest was ERBB2-positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high-level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR-type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.}, } @article {pmid24887297, year = {2014}, author = {Gruel, N and Benhamo, V and Bhalshankar, J and Popova, T and Fréneaux, P and Arnould, L and Mariani, O and Stern, MH and Raynal, V and Sastre-Garau, X and Rouzier, R and Delattre, O and Vincent-Salomon, A}, title = {Polarity gene alterations in pure invasive micropapillary carcinomas of the breast.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {3}, pages = {R46}, pmid = {24887297}, issn = {1465-542X}, mesh = {Axonemal Dyneins/genetics ; Base Sequence ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Calmodulin-Binding Proteins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity/*genetics ; Chaperonins ; Class I Phosphatidylinositol 3-Kinases ; Cytoskeletal Proteins/genetics ; DNA Copy Number Variations ; Exome/genetics ; Female ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/biosynthesis/genetics ; Formins ; Gene Amplification/genetics ; Group II Chaperonins/genetics ; Humans ; Membrane Glycoproteins/genetics ; Membrane Proteins/biosynthesis/genetics ; Microfilament Proteins/biosynthesis ; Molecular Chaperones ; Mutation, Missense ; Neoplasm Invasiveness/*genetics ; Neoplasm Proteins/genetics ; Nuclear Proteins/biosynthesis ; Phosphatidylinositol 3-Kinases/genetics ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; RNA-Binding Proteins ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Retrospective Studies ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Sequence Deletion/genetics ; Serine C-Palmitoyltransferase/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin-Protein Ligases ; }, abstract = {INTRODUCTION: Pure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.

METHODS: Pangenomic analysis (n=39), TP53 (n=43) and PIK3CA (n=41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n=4) and RNA sequencing (n=6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.

RESULTS: Unsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.

CONCLUSION: In our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.}, } @article {pmid24886617, year = {2014}, author = {Wani, N and Nasser, MW and Ahirwar, DK and Zhao, H and Miao, Z and Shilo, K and Ganju, RK}, title = {C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {3}, pages = {R54}, pmid = {24886617}, issn = {1465-542X}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA109527/CA/NCI NIH HHS/United States ; R01 CA153490/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/drug therapy/genetics/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Chemokine CXCL12/*metabolism ; Female ; Humans ; Lung Neoplasms/genetics/mortality/*secondary ; Macrophage Activation/genetics ; Macrophage Colony-Stimulating Factor/biosynthesis ; Macrophages/immunology ; Matrix Metalloproteinase 2/biosynthesis ; Matrix Metalloproteinase 9/biosynthesis ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness/genetics ; Neoplasm Transplantation ; Protein Binding ; RNA Interference ; RNA, Small Interfering ; Receptor, Macrophage Colony-Stimulating Factor/biosynthesis ; Receptors, CXCR/antagonists & inhibitors/biosynthesis/genetics/*metabolism ; STAT3 Transcription Factor/antagonists & inhibitors/genetics/*metabolism ; Tumor Microenvironment ; Vascular Cell Adhesion Molecule-1/biosynthesis ; }, abstract = {INTRODUCTION: Although C-X-C motif chemokine 12 (CXCL12) has been shown to bind to C-X-C chemokine receptor type 7 (CXCR7), the exact molecular mechanism regulations by CXCL12/CXCR7 axis in breast tumor growth and metastasis are not well understood. CXCR7 expression has been shown to be upregulated during pathological processes such as inflammation and cancer.

METHODS: Breast cancer cell lines were genetically silenced or pharmacologically inhibited for CXCR7 and/or its downstream target signal transducer and activator of transcription 3 (STAT3). 4T1 or 4T1 downregulated for CXCR7 and 4T1.2 breast cancer cell lines were injected in mammary gland of BALB/c mice to form tumors, and the molecular pathways regulating tumor growth and metastasis were assessed.

RESULTS: In this study, we observed that CXCL12 enhances CXCR7-mediated breast cancer migration. Furthermore, genetic silencing or pharmacologic inhibition of CXCR7 reduced breast tumor growth and metastasis. Further elucidation of mechanisms revealed that CXCR7 mediates tumor growth and metastasis by activating proinflammatory STAT3 signaling and angiogenic markers. Furthermore, enhanced breast tumorigenicity and invasiveness were associated with macrophage infiltration. CXCR7 recruits tumor-promoting macrophages (M2) to the tumor site through regulation of the macrophage colony-stimulating factor (M-CSF)/macrophage colony-stimulating factor receptor (MCSF-R) signaling pathway. In addition, CXCR7 regulated breast cancer metastasis by enhancing expression of metalloproteinases (MMP-9, MMP-2) and vascular cell-adhesion molecule-1 (VCAM-1). We also observed that CXCR7 is highly expressed in invasive ductal carcinoma (IDC) and metastatic breast tissue in human patient samples. In addition, high CXCR7 expression in tumors correlates with worse prognosis for both overall survival and lung metastasis-free survival in IDC patients.

CONCLUSION: These observations reveal that CXCR7 enhances breast cancer growth and metastasis via a novel pathway by modulating the tumor microenvironment. These findings identify CXCR7-mediated STAT3 activation and modulation of the tumor microenvironment as novel regulation of breast cancer growth and metastasis. These studies indicate that new strategies using CXCR7 inhibitors could be developed for antimetastatic therapy.}, } @article {pmid24886289, year = {2014}, author = {Choi, EJ and Yun, JA and Jabeen, S and Jeon, EK and Won, HS and Ko, YH and Kim, SY}, title = {Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {137}, pmid = {24886289}, issn = {1477-7819}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Adult ; Aged ; Anoctamin-1 ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Chloride Channels/*metabolism ; Fas-Associated Death Domain Protein/*metabolism ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/*metabolism ; Neoplasm Recurrence, Local/*metabolism/pathology ; Neoplasm Staging ; Prognosis ; }, abstract = {BACKGROUND: 11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast.

METHODS: Ninety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival.

RESULTS: FADD expression was associated with T stage (P=0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P=0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P=0.034).

CONCLUSIONS: FADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.}, } @article {pmid24885919, year = {2014}, author = {Xie, R and Wang, Y and Nie, W and Huang, W and Song, W and Wang, Z and Guan, X}, title = {Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma.}, journal = {Cancer biotherapy & radiopharmaceuticals}, volume = {29}, number = {5}, pages = {215-220}, pmid = {24885919}, issn = {1557-8852}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Female ; Humans ; Middle Aged ; RNA-Binding Proteins/*biosynthesis/genetics ; }, abstract = {Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development.}, } @article {pmid24876514, year = {2014}, author = {Bedford, T and Alperstein, A and Nathani, Y and Marx, R and DeVito, P}, title = {A rare presentation of triple-negative apocrine breast carcinoma with metastases.}, journal = {Journal of surgical case reports}, volume = {2014}, number = {5}, pages = {}, pmid = {24876514}, issn = {2042-8812}, abstract = {Apocrine breast carcinoma is a rare subtype of the invasive ductal carcinoma and accounts for as little as 0.3-1% of all breast cancers. It is usually positive for human epidermal growth factor receptor 2 (HER-2) and negative for both estrogen receptor and progesterone receptor. Here we present an exceptionally rare case of apocrine breast carcinoma that is a triple receptor negative with metastases and to our knowledge this is the first published case. This is a significant finding because it implies that the tumor would not respond to the typical hormonal agents. This case highlights the need for studies to elucidate better treatment strategies for these types of patients.}, } @article {pmid24871582, year = {2015}, author = {Thuler, LC and Bergmann, A}, title = {Male breast cancer: clinical-epidemiological characteristics of 1189 Brazilian patients.}, journal = {The aging male : the official journal of the International Society for the Study of the Aging Male}, volume = {18}, number = {2}, pages = {118-123}, doi = {10.3109/13685538.2014.922532}, pmid = {24871582}, issn = {1473-0790}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Brazil/epidemiology ; Breast Neoplasms, Male/*epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/*pathology/therapy ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Radiotherapy ; Registries ; Surgical Procedures, Operative ; }, abstract = {PURPOSE: To describe the clinical-epidemiological features of male patients with breast cancer in Brazil.

METHODS: Data from male patients with breast cancer treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. Descriptive statistics were performed.

RESULTS: A total of 1189 male patients were included. The mean age at diagnosis was 59.6 years (± 13.6). Tumours were categorised as clinical stage I (14.3%), stage II (38.3%), stage III (34.1%) and stage IV (13.3%). The most frequent histological type was invasive ductal carcinoma (83.7%). The first course treatment (alone or combined) consisted of chemotherapy in 53.2%, surgery in 49.2, radiation therapy in 36.8 and hormonal therapy in 21.0%; 3.4% of cases did not receive treatment. Treatment modality varies according to the tumor-node-metastasis (TNM) stage. The inadequate response rate was 15.9%, and 7.4% of patients died after the first course of treatment. Adequate response according to the first-course cancer treatment, after adjusted for clinical stage, was associated with being Caucasian (odds ratio (OR) = 2.50; 95% confidence interval (95% CI): 1.35-4.65) and submitted to chemotherapy (OR = 0.46; 95% CI: 0.28-0.74).

CONCLUSIONS: Male breast cancer diagnosis is often made in the advanced stage. Consequently, patients were subjected to more aggressive treatments, with poorer clinical response.}, } @article {pmid24870789, year = {2014}, author = {Rathore, AS and Goel, MM and Makker, A and Kumar, S and Srivastava, AN}, title = {Is the tumor infiltrating natural killer cell (NK-TILs) count in infiltrating ductal carcinoma of breast prognostically significant?.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {8}, pages = {3757-3761}, doi = {10.7314/apjcp.2014.15.8.3757}, pmid = {24870789}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/pathology ; CD56 Antigen/immunology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Cell Count ; Female ; Humans ; Immunohistochemistry ; Killer Cells, Natural/*immunology ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; }, abstract = {PURPOSE: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast.

MATERIAL AND METHODS: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively.

RESULTS: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (χ2=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (χ2=1.60, p>0.05).

CONCLUSION: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.}, } @article {pmid24868030, year = {2014}, author = {Muss, HB}, title = {Adjuvant chemotherapy in older women with breast cancer: who and what?.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {32}, number = {19}, pages = {1996-2000}, doi = {10.1200/JCO.2013.54.8586}, pmid = {24868030}, issn = {1527-7755}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/diagnosis/*drug therapy/*surgery ; Carcinoma, Ductal, Breast/drug therapy/surgery ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Comorbidity ; Female ; Filgrastim ; Granulocyte Colony-Stimulating Factor/administration & dosage ; Humans ; *Life Expectancy ; Lymphatic Metastasis ; Polyethylene Glycols ; *Quality of Life ; Receptor, ErbB-2/analysis ; Recombinant Proteins/administration & dosage ; Referral and Consultation ; Risk Assessment ; Risk Factors ; Taxoids/administration & dosage ; }, abstract = {A 73-year-old woman has been diagnosed with a mammographically detected grade 3, 2.2-cm invasive ductal carcinoma that is sentinel lymph node negative, estrogen receptor positive (80%), progesterone receptor negative, and human epidermal growth factor receptor 2 negative (0 by immunohistochemistry). A gene expression assay (Oncotype DX, Genomic Health, Redwood City, CA) showed a recurrence score of 28. Except for well-controlled hypertension and some aches and pains in her hands and knees, she has no other major illnesses. Her medications include an antihypertensive, vitamin D, and calcium. She discontinued cigarette smoking 20 years ago and has an occasional glass of wine. She describes her health as good, is fully functional, drives, has had no falls, and provides the majority of care for her sick husband. Her blood pressure is 146/88, her body mass index is 29.7, and her physical examination is normal. She is aware of the benefits and risks of adjuvant endocrine therapy and has been referred to discuss the role of chemotherapy.}, } @article {pmid24866608, year = {2014}, author = {Sohn, YM and Hong, IK and Han, K}, title = {Role of [18F]fluorodeoxyglucose positron emission tomography-computed tomography, sonography, and sonographically guided fine-needle aspiration biopsy in the diagnosis of axillary lymph nodes in patients with breast cancer: comparison of diagnostic performance.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {33}, number = {6}, pages = {1013-1021}, doi = {10.7863/ultra.33.6.1013}, pmid = {24866608}, issn = {1550-9613}, mesh = {Adult ; Aged ; Axilla/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology/*secondary ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; False Negative Reactions ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Middle Aged ; Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy/*methods ; Tomography, X-Ray Computed/methods ; Ultrasonography, Mammary/*methods ; }, abstract = {OBJECTIVES: The aim of this study was to compare the diagnostic performance of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) with that of sonography and sonographically guided fine-needle aspiration (FNA) for determining the preoperative axillary lymph node (ALN) status and to evaluate the factors related to false-negative PET-CT, sonographic, and FNA results in ALN staging of invasive ductal carcinoma.

METHODS: From March 2009 to July 2012, 226 patients had a diagnosis of primary breast cancer. Among these patients, 107 constituted the study population after exclusion of transferred patients and patients with breast cancer other than invasive ductal carcinoma. The diagnostic performance of the modalities was compared with pathologic reports. Univariate and multivariate analyses were used to evaluate the relationship between clinicopathologic factors (symptoms, T stage, hormone receptors, and histologic grade), false-negative results, and true-negative results on PET-CT, sonography, and FNA.

RESULTS: Of the 107 patients, 45 (42.1%) had positive results on final pathologic analysis of ALNs. Sonographically guided FNA had a significantly higher specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve than sonography and PET-CT (P < .01). When sonography and PET-CT were combined, the sensitivity was significantly improved (P = .019) compared with sonography alone. When FNA and PET-CT were combined, the sensitivity and negative predictive value were significantly increased compared with each modality (P < .01).

CONCLUSIONS: Sonographically guided FNA was found to be an excellent diagnostic tool for preoperative evaluation of the ALN status. To obviate the step of sentinel lymph node biopsy for determining the ALN status, combined evaluation of ALNs by these modalities may be more complementary than the use of a single modality.}, } @article {pmid24865535, year = {2014}, author = {Hirota, M and Ogawa, M}, title = {No-touch pancreatectomy for invasive ductal carcinoma of the pancreas.}, journal = {JOP : Journal of the pancreas}, volume = {15}, number = {3}, pages = {243-249}, doi = {10.6092/1590-8577/2502}, pmid = {24865535}, issn = {1590-8577}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/mortality/secondary/*surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology/prevention & control ; Neoplasm Recurrence, Local/pathology/prevention & control ; Neoplastic Cells, Circulating/*pathology ; Pancreatectomy/adverse effects/*methods/mortality ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Prognosis ; Retroperitoneal Space/surgery ; Surgical Instruments ; Touch ; }, abstract = {BACKGROUND: Pancreatectomy is the only effective treatment for cancers of the pancreas. Surgeons usually grasp tumors during pancreatectomy; however, this procedure may increase the risk of squeezing and shedding of the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed surgical techniques for no-touch pancreatectomy.

METHODS: From April 2008 through September 2013, 52 patients have been operated on no-touch pancreatectomy for invasive ductal carcinoma of the pancreas by a single operator (M.H.). Among them, 40 received pancreatoduodenectomy (PD), and 12 did distal pancreatectomy (DP). Twenty two cases (42%) required SMV-PV resection. This is a study to see if pancreatectomy can be technically done using a no-touch surgical technique without deteriorating the post-operative prognosis. During the procedure, the pancreatic tumor is neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection of the retroperitoneal tissue (leftward and posterior margins for PD and rightward and posterior margins for DP), we use a hanging and clamping maneuver and dissection behind Gerota fascia.

RESULTS: Overall 2- and 5-year survival rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68 months). Recurrence free 2- and 5-year survival rates were 49 and 31%, respectively. The 5-year survival rates of patients with JPS-stage III and those with JPS-stage IV were 57 and 20%, respectively. The 5-year survival rates of patients with UICC-stage IIA and those with UICC- stage IIB were 49 and 39%, respectively. Patients with UICC-stage III or IV did not survive for more than 2 years.

CONCLUSIONS: No-touch pancreatectomy has many theoretic advantages that merit further investigation in future randomized controlled trials.}, } @article {pmid24863566, year = {2014}, author = {Coates, SJ and Mitchell, K and Olorunnipa, OB and DeSimone, RA and Otterburn, DM and Simmons, RM}, title = {An unusual breast lesion: granular cell tumor of the breast with extensive chest wall invasion.}, journal = {Journal of surgical oncology}, volume = {110}, number = {3}, pages = {345-347}, doi = {10.1002/jso.23640}, pmid = {24863566}, issn = {1096-9098}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis ; Female ; Granular Cell Tumor/*pathology/surgery ; Humans ; Incidental Findings ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Sentinel Lymph Node Biopsy ; Thoracic Wall/*pathology/surgery ; }, abstract = {Granular cell tumors (GCT) are generally benign soft tissue tumors. When located in the breast, they may be misdiagnosed as more typical tumors, such as invasive ductal carcinoma, based on misleading clinical or radiologic features. GCTs are frequently found in the setting of a known malignancy. We report the case of a patient with a large infra-mammary fold GCT, the management of which required a multidisciplinary operative approach due to extensive chest wall invasion.}, } @article {pmid24862985, year = {2014}, author = {Takagi, K and Moriguchi, T and Miki, Y and Nakamura, Y and Watanabe, M and Ishida, T and Yamamoto, M and Sasano, H and Suzuki, T}, title = {GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.}, journal = {Cancer science}, volume = {105}, number = {5}, pages = {600-607}, pmid = {24862985}, issn = {1349-7006}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Disease-Free Survival ; Female ; GATA4 Transcription Factor/genetics/*metabolism ; Gene Expression ; Humans ; Immunohistochemistry ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Recurrence, Local/genetics/*pathology ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Transcriptional GATA factors are known lineage selector genes and regulate a variety of biological processes including specification and differentiation of tissues. In the present study, we examined expression profiles of six GATA factor genes in invasive ductal carcinomas (IDC) of the breast using microarray analysis (n = 20) and found that GATA4 expression was closely correlated with recurrence in patients. Because the significance of GATA4 has remained largely unknown in breast carcinoma, we further immunolocalized GATA4 in ductal carcinoma in situ (DCIS) of the breast (n = 48) and IDC (n = 163). GATA4 immunoreactivity was detected in the nuclei of carcinoma cells and was positive in 27% of DCIS and 31% of IDC cases. GATA4 status was significantly associated with nuclear grade and van Nuys classification in DCIS and was positively associated with distant metastasis, histological grade and HER2 status, but negatively correlated with progesterone receptor labeling index in IDC. Subsequent multivariate analysis demonstrated that GATA4 status was an independent prognostic factor for both disease-free and breast cancer-specific survival of IDC patients. All of these results indicate that GATA4 plays important roles in the progression of breast carcinoma from an early stage and that immunohistochemical GATA4 status is considered a potent prognostic factor in human breast cancer patients.}, } @article {pmid24857380, year = {2014}, author = {Wallace, AS and Xiang, D and Hockman, L and Arya, M and Jeffress, J and Wang, Z and Dale, PS}, title = {Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {40}, number = {10}, pages = {1245-1249}, doi = {10.1016/j.ejso.2014.04.007}, pmid = {24857380}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Cohort Studies ; Disease Progression ; Female ; Humans ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/surgery ; Retrospective Studies ; }, abstract = {AIM: Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC).

METHODS: Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p < 0.05 is considered significant.

RESULTS: A total of 148 patients with ILC or LCIS were identified. Forty-four (54%) patients with only ILC, and 37 (46%) patients with ILC/LCIS were identified. Median age at diagnosis was 62 for ILC and 64 years for ILC/LCIS (p = 0.8). In patients with ILC, total mastectomy was the predominant treatment modality in 28 of 44 (64%) patients, while 18 of 37 (49%) patients with ILC/LCIS underwent breast conservation therapy (p = 0.3). Median largest tumor diameter was 35 mm (range 1-110) for ILC, and 15 mm (range 5-85) for ILC/LCIS (p = 0.03). Nodal status was positive in 17 of 39 (44%) ILC and 13 of 34 (38%) ILC/LCIS (p = 0.6).

CONCLUSIONS: The 46% incidence of LCIS associated with ILC in our cohort study is similar to that reported for ductal carcinoma in situ identified with invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship.}, } @article {pmid24852912, year = {2014}, author = {Morin, B and Bretz-Grenier, MF and Foessel, L and Guillaume, A and Gangi, A and Mathelin, C}, title = {[MRI-guided breast microbiospy or macrobiopsy: which is the best option for a small tumor?].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {42}, number = {6}, pages = {462-466}, doi = {10.1016/j.gyobfe.2014.04.007}, pmid = {24852912}, issn = {1769-6682}, mesh = {Aged ; Biopsy/instrumentation/*methods ; Biopsy, Fine-Needle ; Biopsy, Large-Core Needle ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; }, abstract = {The choice of the optimum therapeutic strategy for breast cancer depends on the histological diagnosis of the sample obtained by biopsy. The microbiopsy is the preferred method as it provides an accurate diagnosis of the histological type as well as the main prognostic factors, whilst being simple, fast and inexepensive. However, some infraclinic breast tumors are not accessible by conventional guidance due to excessive depth inside the breast, their small size or technical inability to image them by mammography or ultrasonography. In those cases, the MRI guidance may help to perform the biopsy. Most MRI biopsies are made by large-core needle that are known to alter the histological structure of the tumor and to disturb the anatomopatholgical analysis (size and surgical margin). Those are very important elements to know before treatment. Our case report details an original technique of MRI microbiopsy of a deep 4mm opacity found on the occasion of a patient's mammography. The operative specimen revealed an invasive ductal carcinoma of 4mm diameter which scored III on the Elston and Ellis scale (oestrogen and progesterone receptors tested negative and HER-2 was over-expressed). It was associated with a high grade in situ ductal carcinoma. No systemic treatment was prescribed due to the small size of the carcinoma. The development of partially or totally amagnetic microbiopsy pistols would help perform microbiopses guided by MRI.}, } @article {pmid24848193, year = {2015}, author = {Santangelo, G and Vitale, C and Trojano, L and Picillo, M and Moccia, M and Pisano, G and Pezzella, D and Cuoco, S and Erro, R and Longo, K and Pellecchia, MT and Amboni, M and De Rosa, A and De Michele, G and Barone, P}, title = {Relationship between apathy and cognitive dysfunctions in de novo untreated Parkinson's disease: a prospective longitudinal study.}, journal = {European journal of neurology}, volume = {22}, number = {2}, pages = {253-260}, doi = {10.1111/ene.12467}, pmid = {24848193}, issn = {1468-1331}, mesh = {Aged ; Apathy/*physiology ; Cognition Disorders/*etiology/physiopathology ; Disease Progression ; Executive Function/*physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/physiopathology ; }, abstract = {BACKGROUND AND PURPOSE: Apathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy.

METHODS: Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests.

RESULTS: According to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A-A+), 37 patients never experienced apathy (A-A-) and eight patients showed apathy at the baseline only (A+A-). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A-A- on visuospatial and frontal tests; A-A+ had lower scores than A-A- on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up.

CONCLUSIONS: The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.}, } @article {pmid24846495, year = {2014}, author = {Holmes, DR}, title = {Intraoperative radiotherapy in breast conserving surgery.}, journal = {Journal of surgical oncology}, volume = {110}, number = {1}, pages = {68-74}, doi = {10.1002/jso.23620}, pmid = {24846495}, issn = {1096-9098}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; }, mesh = {Breast Neoplasms/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; *Mastectomy, Segmental ; *Radiotherapy ; }, abstract = {Intraoperative radiotherapy (IORT) of the breast is the administration of a single fraction of radiation to the tumor bed while shielding low risk and uninvolved tissues from the effects of radiation. The TARGIT A and ELIOT trials demonstrate efficacy of IORT when administered at the time of lumpectomy to post-menopausal women with low to intermediate grade, lymph node negative, invasive ductal carcinoma, consistent with international guidelines defining suitable candidates for accelerated partial breast radiotherapy.}, } @article {pmid24842702, year = {2014}, author = {Picillo, M and Erro, R and Amboni, M and Longo, K and Vitale, C and Moccia, M and Pierro, A and Scannapieco, S and Santangelo, G and Spina, E and Orefice, G and Barone, P and Pellecchia, MT}, title = {Gender differences in non-motor symptoms in early Parkinson's disease: a 2-years follow-up study on previously untreated patients.}, journal = {Parkinsonism & related disorders}, volume = {20}, number = {8}, pages = {850-854}, doi = {10.1016/j.parkreldis.2014.04.023}, pmid = {24842702}, issn = {1873-5126}, mesh = {Aged ; Antiparkinson Agents/*adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Parkinson Disease/*complications/*drug therapy ; Sex Characteristics ; }, abstract = {BACKGROUND: We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.

METHODS: In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment.

RESULTS: One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features.

CONCLUSIONS: In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.}, } @article {pmid24842355, year = {2014}, author = {Vázquez Vicente, D and Di Fiore, HA and Garcia-Foncillas, J and Plaza Arranz, J}, title = {Endometrial adenocarcinoma in one horn of a didelphic uterus with vaginal duplication.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24842355}, issn = {1757-790X}, mesh = {Abnormalities, Multiple/diagnosis ; Adenocarcinoma/complications/*diagnosis/surgery ; Endometrial Neoplasms/complications/*diagnosis/surgery ; Endosonography/methods ; Female ; Follow-Up Studies ; Humans ; Hysterectomy/methods ; Hysteroscopy/methods ; Laparoscopy/methods ; Magnetic Resonance Imaging/methods ; Middle Aged ; Ovariectomy/methods ; Postmenopause ; Risk Assessment ; Treatment Outcome ; Urogenital Abnormalities/*diagnosis/surgery ; Uterine Hemorrhage/diagnosis/etiology ; Uterus/*abnormalities/surgery ; Vagina/*abnormalities/surgery ; }, abstract = {A 59-year-old female patient presented with vaginal bleeding. A didelphic uterus with vaginal duplication was diagnosed on the basis of physical examination and radiology tests. Biopsy revealed an endometrial cancer in the left horn, while the right was atrophic. Laparoscopic hysterectomy, bilateral salphingo-oophorectomy, pelvic and para-aortic lymphadenectomy were performed. According to Federation International of Gynecology and Obstetrics (FIGO) staging the tumour was classified Ib. The adjuvant therapy was vaginal cuff brachytherapy. After 6 months, she has no evidence of the disease.}, } @article {pmid24842280, year = {2014}, author = {Miyai, K and Divatia, MK and Shen, SS and Miles, BJ and Ayala, AG and Ro, JY}, title = {Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion.}, journal = {Human pathology}, volume = {45}, number = {8}, pages = {1572-1581}, doi = {10.1016/j.humpath.2014.03.011}, pmid = {24842280}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/*pathology ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P=.00016), larger tumor volume (P=.025), and more advanced pT stage (P=.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests (P=.0045 and P=.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P=.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance.}, } @article {pmid24841533, year = {2014}, author = {Engstrom, LM and Brinkmeyer, MK and Ha, Y and Raetz, AG and Hedman, B and Hodgson, KO and Solomon, EI and David, SS}, title = {A zinc linchpin motif in the MUTYH glycosylase interdomain connector is required for efficient repair of DNA damage.}, journal = {Journal of the American Chemical Society}, volume = {136}, number = {22}, pages = {7829-7832}, pmid = {24841533}, issn = {1520-5126}, support = {T32 ES007058/ES/NIEHS NIH HHS/United States ; R01 CA067985/CA/NCI NIH HHS/United States ; T32 ES007059/ES/NIEHS NIH HHS/United States ; P41GM103393/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; CA069785/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cysteine/chemistry/genetics ; DNA Damage ; DNA Glycosylases/*chemistry/genetics ; DNA Repair Enzymes/*chemistry ; Humans ; Kinetics ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Protein Conformation ; Serine/chemistry/genetics ; Zinc Compounds/*chemistry ; }, abstract = {Mammalian MutY glycosylases have a unique architecture that features an interdomain connector (IDC) that joins the catalytic N-terminal domain and 8-oxoguanine (OG) recognition C-terminal domain. The IDC has been shown to be a hub for interactions with protein partners involved in coordinating downstream repair events and signaling apoptosis. Herein, a previously unidentified zinc ion and its coordination by three Cys residues of the IDC region of eukaryotic MutY organisms were characterized by mutagenesis, ICP-MS, and EXAFS. In vitro kinetics and cellular assays on WT and Cys to Ser mutants have revealed an important function for zinc coordination on overall protein stability, iron-sulfur cluster insertion, and ability to mediate DNA damage repair. We propose that this "zinc linchpin" motif serves to structurally organize the IDC and coordinate the damage recognition and base excision functions of the C- and N-terminal domains.}, } @article {pmid24838727, year = {2014}, author = {Lai, Q and Wang, T and Guo, Q and Zhang, Y and Wang, Y and Yuan, L and Ling, R and He, Y and Wang, W}, title = {Positive correlation between the expression of hEag1 and HIF-1α in breast cancers: an observational study.}, journal = {BMJ open}, volume = {4}, number = {5}, pages = {e005049}, pmid = {24838727}, issn = {2044-6055}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/diagnosis/*metabolism ; Ether-A-Go-Go Potassium Channels/*biosynthesis ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis ; Immunohistochemistry ; Middle Aged ; Prognosis ; Young Adult ; }, abstract = {OBJECTIVES: To explore the expression patterns of Eag1 (ether á go-go 1) and HIF-1α (hypoxia-inducible factor 1α) in a cohort of patients with breast cancer.

SETTING: Department of general surgery in an upper first-class hospital in Xi'an, China.

PARTICIPANTS: A total of 112 female Han Chinese patients with a diagnosis of invasive ductal carcinoma were included. Patients with main internal diseases, such as cardiovascular, endocrine, gastroenterological, haematological, infectious diseases, etc, were excluded.

Expression profiles of Eag1 and HIF-1α.

RESULTS: Eag1 and HIF-1α were overexpressed in the tumour tissues compared with the pair-matched control tissues, p=0.002 and <0.001, respectively. The expression of Eag1 and HIF-1α was negatively correlated with tumour size, p=0.032 and p=0.025, respectively, and lymph node status (p=0.040, p=0.032, respectively). The coexpression of Eag1 and HIF-1α was correlated with tumour size (p=0.012), lymph node status (p=0.027) and tumour stage (p=0.036). HIF-1α has a strong correlation with hEag1 expression (κ=0.731, p<0.001).

CONCLUSIONS: HIF-1α expression has a strong correlation with hEag1 expression. We are the first to attempt to explore the correlation at the population level.}, } @article {pmid24838367, year = {2014}, author = {Paul Wright, G and Davis, AT and Koehler, TJ and Melnik, MK and Chung, MH}, title = {Hormone receptor status does not affect prognosis in metaplastic breast cancer: a population-based analysis with comparison to infiltrating ductal and lobular carcinomas.}, journal = {Annals of surgical oncology}, volume = {21}, number = {11}, pages = {3497-3503}, doi = {10.1245/s10434-014-3782-7}, pmid = {24838367}, issn = {1534-4681}, mesh = {Aged ; Breast Neoplasms/metabolism/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*mortality/pathology/surgery ; Carcinoma, Lobular/metabolism/*mortality/pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Metaplasia/metabolism/*mortality/pathology/surgery ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; SEER Program ; Survival Rate ; }, abstract = {BACKGROUND: Metaplastic breast cancer is a rare histologic variant among breast cancers. We sought to investigate the impact of hormone receptor status in metaplastic breast cancer and compare outcomes with common histologic variants of breast cancer.

METHODS: The study was performed utilizing the Surveillance, Epidemiology, and End Results database. A query was made for patients with metaplastic breast cancer from 2000 to 2010. A separate query identified all patients with infiltrating ductal (IDC) or lobular (ILC) carcinoma during the same period. Effect of hormone receptor status was evaluated using Cox regression analysis. Significance was assessed for p < 0.05.

RESULTS: A total of 2,338 patients with metaplastic breast cancer were available for study. Most tumors were hormone receptor negative (79.0 %) and greater than or equal to grade 3 (82.9 %). For comparison, 382,667 and 44,813 patients with IDC and ILC, respectively, were obtained. Overall 5-year survival for metaplastic breast cancer was 62.2 % compared with 81.2 % for IDC (p < 0.001) and 80.2 % for ILC (p < 0.001). For metaplastic cases, no difference in 5-year survival was found between hormone-positive and hormone-negative tumors (65.7 vs. 63.5 %; p = 0.70). Multivariate analysis demonstrated metaplastic histology as an independent risk factor for cancer-related mortality both among hormone-positive (hazard ratio [HR] 2.4; 95 % confidence interval [CI] 1.8-3.0; p < 0.001) and hormone-negative (HR 1.7; 95 % CI 1.5-1.9; p < 0.001) breast cancers.

CONCLUSION: Metaplastic breast cancer is an aggressive histologic variant that portends a poor prognosis compared with common breast cancer subtypes. Contrary to other breast cancers, hormone receptor positivity does not improve prognosis in metaplastic breast cancer.}, } @article {pmid24835032, year = {2014}, author = {Sugimoto, M and Mitsunaga, S and Yoshikawa, K and Kato, Y and Gotohda, N and Takahashi, S and Konishi, M and Ikeda, M and Kojima, M and Ochiai, A and Kaneko, H}, title = {Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {11}, pages = {1900-1908}, doi = {10.1016/j.ejca.2014.04.010}, pmid = {24835032}, issn = {1879-0852}, mesh = {Aged ; Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Enteric Nervous System/*pathology ; Female ; Humans ; Immunohistochemistry ; Macrophages/*pathology ; Male ; Mice ; Neoplasm Invasiveness ; Pancreatic Neoplasms/drug therapy/*pathology/surgery ; Prognosis ; Scavenger Receptors, Class A/metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: Neural invasion is a characteristic pattern of invasion and an important prognostic factor for invasive ductal carcinoma (IDC) of the pancreas. M2 macrophages have reportedly been associated with poor prognosis in various cancers. The aim of the present study was to investigate the prognostic impact of M2 macrophages at extrapancreatic nerve plexus invasion (plx-inv) of pancreatic IDC.

METHODS: Participants comprised 170 patients who underwent curative pancreaticoduodenectomy for pancreatic IDC. Immunohistochemical examination of surgical specimens was performed by using CD204 as an M2 macrophage marker, and the area of immunopositive cells was calculated automatically. Prognostic analyses of clinicopathological factors including CD204-positive cells at plx-inv were performed.

RESULTS: Plx-inv was observed in 91 patients (53.5%). Forty-eight patients showed a high percentage of CD204-positive cell area at plx-inv (plx-inv CD204%(high)). Plx-inv CD204%(high) was an independent predictor of poor outcomes for overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Patients with plx-inv CD204%(high) showed a shorter time to peritoneal dissemination (P<0.001) and locoregonal recurrence (P<0.001). In patients who underwent adjuvant chemotherapy, plx-inv CD204%(high) was correlated with shorter OS (P=0.011) and DFS (P=0.038) in multivariate analysis.

CONCLUSIONS: Plx-inv CD204%(high) was associated with shortened OS and DFS and early recurrence in the peritoneal cavity and locoregional space. The prognostic value of plx-inv CD204%(high) was also applicable to patients who received adjuvant chemotherapy. High accumulation of M2 macrophages at plx-inv represents an important predictor of poor prognosis.}, } @article {pmid24833443, year = {2015}, author = {Matsuda, H and Takahashi, Y and Nakata, K and Kitamura, A and Kakizaki, H}, title = {No Intense 18F-Fluorodeoxyglucose Uptake in Positron Emission Tomography of a Metastatic Orbital Tumor From Breast Carcinoma.}, journal = {Ophthalmic plastic and reconstructive surgery}, volume = {31}, number = {4}, pages = {e95-8}, doi = {10.1097/IOP.0000000000000115}, pmid = {24833443}, issn = {1537-2677}, mesh = {Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/secondary ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Radical ; Medroxyprogesterone/therapeutic use ; Middle Aged ; Muscle Neoplasms/diagnostic imaging/secondary ; Oculomotor Muscles/diagnostic imaging ; Orbital Neoplasms/*diagnostic imaging/secondary ; Paclitaxel/therapeutic use ; *Positron-Emission Tomography ; Radiopharmaceuticals/*metabolism ; Vision Disorders/diagnosis ; }, abstract = {A 47-year-old woman with a history of invasive ductal carcinoma in the right breast reported decreased vision in the OD for the past 3 months. Her best corrected visual acuity was 0.1 OD and 1.0 OS. T1-weighted MRI revealed enlargement of the right lateral rectus muscle with a faint tumor outline and no contrast enhancement in the lesion. F-fluorodeoxyglucose positron emission tomography did not demonstrate intense uptake at the lesion. Because the patient demonstrated optic neuropathy due to compression by the enlarged muscle, balanced orbital decompression (of the deep lateral and medial orbital walls) was performed simultaneously with a tumor biopsy. Visual acuity of the OD was dramatically improved to 1.0. The histopathological examination demonstrated similar findings to her breast carcinoma. F-fluorodeoxyglucose positron emission tomography does not always show a positive result for an orbital tumor that has metastasized from the breast.}, } @article {pmid24821579, year = {2014}, author = {Isidro, A and Malgosa, A and Huber, B}, title = {Mummification of the lower urinary system in a Coptic individual from ancient Egypt.}, journal = {European urology}, volume = {66}, number = {2}, pages = {393-394}, doi = {10.1016/j.eururo.2014.04.024}, pmid = {24821579}, issn = {1873-7560}, mesh = {Adult ; Anthropology ; Egypt, Ancient ; History, Ancient ; Humans ; Male ; Mummies/*history ; *Seminal Vesicles ; *Ureter ; *Urinary Bladder/blood supply ; }, } @article {pmid24818623, year = {2014}, author = {Ozülkü, M and Calişkan, M and Güllü, H and Erdoğan, D and Calişkan, Z and Müderrisoğlu, H}, title = {Interrelation of RDW and coronary flow reserve in patient with idiopathic dilated cardiomyopathy.}, journal = {Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology}, volume = {14}, number = {4}, pages = {342-348}, doi = {10.5152/akd.2014.4775}, pmid = {24818623}, issn = {1308-0032}, mesh = {Cardiomyopathy, Dilated/blood/diagnostic imaging/*physiopathology ; Case-Control Studies ; Cholesterol/blood ; Erythrocytes/*physiology ; Female ; Fractional Flow Reserve, Myocardial/*physiology ; Humans ; Male ; Microcirculation/*physiology ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Ultrasonography ; }, abstract = {OBJECTIVE: Idiopathic dilated cardiomyopathy (IDC) impairs and reduces coronary flow reserve (CFR). High level of red cell distribution width (RDW) is an independent risk factor for cardiovascular diseases. Therefore, in this observational case-control study we have aimed to determine whether RDW level is associated with CFR impairment in patients with IDC.

METHODS: We examined 36 patients with IDC and 35 healthy subjects formed as a control group. In addition to this, patients with IDC were divided into two subgroups according to their CFR levels [normal CFR group (CFR value ≥2) and lower CFR group (CFR value<2)]. Control and patients groups were compared using the student t-test for multiple comparisons. The subgroups were compared using the Mann-Whitney U test for continuous variables and chi-square for categorical variables. The Pearson's and Spearman correlation analysis was used to test the possible associations between CFR and the study variables as appropriate. The receiver-operating characteristic (ROC) curve was determined to evaluate the predictive performance of RDW to detect low CFR.

RESULTS: There were no significantly differences between the lower and higher CFR groups' clinical data, baseline hemodynamic, medication and biochemical data except RDW and high-sensitivity C-reactive protein levels. We found that RDW level was a good predictor of low CFR at the receiver-operating characteristic curve. The area under the curve (AUC) was 73% (95% confidence interval between 0.56-0.90 is 95%, p: 0.018) After adjusting potential confounders include age, body-mass index, blood pressure, lipid and glucose, RDW independently associated with CFR level (Beta:-0.374; p=0.015) and hsCRP value (Beta:-0.520; p=0.001) were the independent predictors of lower CFR.

CONCLUSION: Results showed that there was an independent correlation between RDW level and CFR level in patients with IDC.}, } @article {pmid24817980, year = {2014}, author = {Niu, Y and Liao, X and Li, X and Zhao, L}, title = {Breast carcinoma with osteoclastic giant cells: case report and review of the literature.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {4}, pages = {1788-1791}, pmid = {24817980}, issn = {1936-2625}, mesh = {Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Female ; Humans ; Mammography ; Mastectomy ; Middle Aged ; Osteoclasts/*pathology ; Treatment Outcome ; }, abstract = {Breast carcinoma with osteoclastic giant cells (OGCs) are uncommon. Here, we report a 46-year-old woman with a painless lump in her left breast that has been proved clinically and radiographically. Microscopical examination showed OGCs accompanying invasive ductal carcinoma. Immunohistochemical assay revealed that OGCs derived from macrophages. Despite positive lymph node metastasis, the patient has been well without evidence of recurrence or metastasis one year after the operation. To date, the influence of OGCs on the prognosis of patients is still controversial. Our case may provide insights into further understanding beast carcinoma with OGCs.}, } @article {pmid24815467, year = {2014}, author = {Kim, H and Youk, JH and Kim, JA and Gweon, HM and Jung, WH and Son, EJ}, title = {US-guided 14G core needle biopsy: comparison between underestimated and correctly diagnosed breast cancers.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {7}, pages = {3179-3183}, doi = {10.7314/apjcp.2014.15.7.3179}, pmid = {24815467}, issn = {2476-762X}, mesh = {Adult ; Aged ; *Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis ; *Diagnostic Errors ; Female ; Humans ; Hyperplasia/diagnosis ; Image-Guided Biopsy ; Mammography ; Middle Aged ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {BACKGROUND: The purpose of study was to evaluate radiologic or clinical features of breast cancer undergoing ultrasound (US)-guided 14G core needle biopsy (CNB) and analyze the differences between underestimated and accurately diagnosed groups.

MATERIALS AND METHODS: Of 1,898 cases of US-guided 14G CNB in our institute, 233 cases were proven to be cancer by surgical pathology. The pathologic results from CNB were invasive ductal carcinoma (IDC) (n=157), ductal carcinoma in situ (DCIS) (n=40), high-risk lesions in 22 cases, and benign in 14 cases. Among high-risk lesions, 7 cases of atypical ductal hyperplasia (ADH) were reported as cancer and 11 cases of DCIS were proven IDC in surgical pathology. Some 29 DCIS cases and 157 cases of IDC were correctly diagnosed with CNB. The clinical and imaging features between underestimated and accurately diagnosed breast cancers were compared.

RESULTS: Of 233 cancer cases, underestimation occurred in 18 lesions (7.7%). Among underestimated cancers, CNB proven ADH (n=2) and DCIS (n=11) were diagnosed as IDC and CNB proven ADH (n=5) were diagnosed at DCIS finally. Among the 186 accurately diagnosed group, the CNB results were IDC (n=157) and DCIS (n=29). Comparison of underestimated and accurately diagnosed groups for BI-RADS category, margin of mass on mammography and US and orientation of lesion on US revealed statistically significant differences.

CONCLUSIONS: Underestimation of US-guided 14G CNB occurred in 7.7% of breast cancers. Between underestimated and correctly diagnosed groups, BI-RADS category, margin of the mass on mammography and margin and orientation of the lesions on US were different.}, } @article {pmid24810926, year = {2014}, author = {Calvano Filho, CM and Calvano-Mendes, DC and Carvalho, KC and Maciel, GA and Ricci, MD and Torres, AP and Filassi, JR and Baracat, EC}, title = {Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {8}, pages = {7733-7741}, pmid = {24810926}, issn = {1423-0380}, mesh = {Breast/metabolism ; Carcinoma, Ductal, Breast/genetics ; Female ; Forkhead Box Protein O1 ; Forkhead Transcription Factors/genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*analysis ; Triple Negative Breast Neoplasms/*genetics ; }, abstract = {New concepts in epigenetics, microRNAs, and gene expression analysis have significantly enhanced knowledge of cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression by base pairing with target messenger RNAs (mRNAs), resulting in the repression of translation or the degradation of mRNA. To compare the carcinogenic process in tumors with different prognoses, we used real-time RT-PCR to evaluate the miRNA expression profiles of 24 triple-negative breast invasive ductal carcinoma, 20 luminal A breast invasive ductal carcinoma, and 13 normal breast parenchyma controls. We extracted total RNA from tissues fixed in formol and embedded in paraffin (FFPE). Results revealed the upregulation of miR-96-5p (9.35-fold; p = 0.000115), miR-182-5p (7.75-fold; p = 0.000033), miR-7-5p (6.71-fold; p = 0.015626), and miR-21-5p (6.10-fold; p = 0.000000) in tumors group. In addition, the expression of miR-125b-5p (4.49-fold; p = 0.000000) and miR-205-5p (4.36-fold; p = 0.006098) was downregulated. When the expression profiles of triple-negative and luminal A tumors were compared, there was enhanced expression of miR-17-5p (4.27-fold; p = 0.000664), miR-18a-5p (9.68-fold; p = 0.000545), and miR-20a-5 (4.07-fold; p = 0.001487) in the triple-negative tumors compared with luminal A. These data suggest that there is a similar regulation of certain miRNAs in triple-negative and luminal A tumors. However, it is possible that differences in the expression of miR-17-92 cluster will explain the phenotypic differences between these molecular tumor subtypes.}, } @article {pmid24799764, year = {2014}, author = {Stumpfova, Z and Hezova, R and Meli, AC and Slaby, O and Michalek, J}, title = {MicroRNA profiling of activated and tolerogenic human dendritic cells.}, journal = {Mediators of inflammation}, volume = {2014}, number = {}, pages = {259689}, pmid = {24799764}, issn = {1466-1861}, mesh = {Cells, Cultured ; Dendritic Cells/drug effects/*metabolism ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-10/pharmacology ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; MicroRNAs/*genetics ; Transforming Growth Factor beta/pharmacology ; }, abstract = {Dendritic cells (DCs) belong to the immune system and are particularly studied for their potential to direct either an activated or tolerogenic immune response. The roles of microRNAs (miRNAs) in posttranscriptional gene expression regulation are being increasingly investigated. This study's aim is to evaluate the miRNAs' expression changes in prepared human immature (iDCs), activated (aDCs), and tolerogenic dendritic cells (tDCs). The dendritic cells were prepared using GM-CSF and IL-4 (iDC) and subsequently maturated by adding LPS and IFN-γ (aDC) or IL-10 and TGF-β (tDC). Surface markers, cytokine profiles, and miRNA profiles were evaluated in iDC, tDC, and aDC at 6 h and 24 h of maturation. We identified 4 miRNAs (miR-7, miR-9, miR-155 and miR-182), which were consistently overexpressed in aDC after 6 h and 24 h of maturation and 3 miRNAs (miR-17, miR-133b, and miR-203) and miR-23b cluster solely expressed in tDC. We found 5 miRNAs (miR-10a, miR-203, miR-210, miR-30a, and miR-449b) upregulated and 3 miRNAs downregulated (miR-134, miR-145, and miR-149) in both tDC and aDC. These results indicate that miRNAs are specifically modulated in human DC types. This work may contribute to identifying specific modulating miRNAs for aDC and tDC, which could in the future serve as therapeutic targets in the treatment of cancer and autoimmune diseases.}, } @article {pmid24797703, year = {2014}, author = {Topps, A and Clay, V and Absar, M and Howe, M and Lim, Y and Johnson, R and Bundred, N}, title = {The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {40}, number = {7}, pages = {813-817}, doi = {10.1016/j.ejso.2014.03.026}, pmid = {24797703}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biopsy, Fine-Needle/methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Carcinoma, Lobular/diagnostic imaging/*pathology/surgery ; Cohort Studies ; Databases, Factual ; Female ; Humans ; Image-Guided Biopsy/methods ; Lymph Node Excision/methods ; Lymph Nodes/*pathology/*surgery ; Mastectomy/methods ; Middle Aged ; Neoplasm Staging ; Preoperative Care/methods ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy/methods ; Ultrasonography ; }, abstract = {INTRODUCTION: Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC).

METHOD: Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND).

RESULTS: A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001).

CONCLUSION: AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures.}, } @article {pmid24795533, year = {2014}, author = {Zahir, MN and Minhas, K and Shabbir-Moosajee, M}, title = {Pleomorphic lobular carcinoma of the male breast with axillary lymph node involvement: a case report and review of literature.}, journal = {BMC clinical pathology}, volume = {14}, number = {}, pages = {16}, pmid = {24795533}, issn = {1472-6890}, abstract = {BACKGROUND: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.

CASE PRESENTATION: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. Physical examination revealed bilateral gynaecomastia along with a well circumscribed subareolar mass and palpable lymphadenopathy in the ipsilateral axilla. The breast nodule revealed atypical cells on fine needle aspiration biopsy and the patient underwent a modified radical mastectomy after systemic surveillance was negative for metastatic disease. The lesion was reported as grade III pleomorphic lobular carcinoma with a lack of E-cadherin expression on immunohistochemistry and the neoplastic cells exhibited strong positivity for estrogen receptor in the absence of Her2 gene amplification. Six out of the eleven dissected regional lymph nodes showed evidence of disease. The patient completed 4 cycles of adjuvant chemotherapy without evidence of recurrent disease and was subsequently lost to follow up.

CONCLUSIONS: Although invasive lobular carcinomas comprise 12% of all female breast cancers, they are very rare in males due to lack of acini and lobules in the normal male breast. Pleomorphic lobular carcinoma, an aggressive variant of ILC is even rarer in males. Chronic consumption of ethanol by our patient may have resulted in some degree of hepatic impairment with resultant hyperestrogenism. This in theory may have been the cause of his gynaecomastia, resultant breast cancer and is a plausible explanation for development of the invasive lobular subtype in a male. The prognosis and clinicopatholocial features of pleomorphic lobular carcinoma in men are less clearly defined due to its rarity. Additional studies are hence necessary to improve our understanding of this disease in males.}, } @article {pmid24794782, year = {2014}, author = {Li, X and Luo, R and Jiang, R and Kong, H and Tang, Y and Shu, Y and Hua, W}, title = {The prognostic use of serum concentrations of cardiac troponin-I, CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy.}, journal = {Heart & lung : the journal of critical care}, volume = {43}, number = {3}, pages = {219-224}, doi = {10.1016/j.hrtlng.2014.03.001}, pmid = {24794782}, issn = {1527-3288}, mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/diagnostic imaging/mortality ; Cohort Studies ; Creatine Kinase, MB Form/*blood ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myoglobin/*blood ; Prognosis ; Proportional Hazards Models ; Troponin I/*blood ; }, abstract = {OBJECTIVE: To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC).

BACKGROUND: It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM).

METHODS: A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality.

RESULTS: Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI ≤ 0.05 ng/mL (37.5% vs 15%, log-rank χ(2) = 18.423, P < 0.001). After adjustment for other factors associated with prognosis at baseline, serum cTnI >0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients.

CONCLUSION: Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC.}, } @article {pmid24790704, year = {2014}, author = {Mohamed, MM and Sabet, S and Peng, DF and Nouh, MA and El-Shinawi, M and El-Rifai, W}, title = {Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis.}, journal = {Oxidative medicine and cellular longevity}, volume = {2014}, number = {}, pages = {787195}, pmid = {24790704}, issn = {1942-0994}, mesh = {Breast/pathology ; Breast Neoplasms/enzymology/*pathology ; *DNA Methylation ; Down-Regulation ; Female ; Glutathione Peroxidase/*genetics/metabolism ; Humans ; Middle Aged ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; }, abstract = {Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients' in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients' clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.}, } @article {pmid24789732, year = {2014}, author = {Erro, R and Santangelo, G and Barone, P and Picillo, M and Amboni, M and Longo, K and Giordano, F and Moccia, M and Allocca, R and Pellecchia, MT and Vitale, C}, title = {Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease?.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {27}, number = {4}, pages = {276-281}, doi = {10.1177/0891988714532015}, pmid = {24789732}, issn = {0891-9887}, mesh = {Aged ; Cognitive Dysfunction/complications/diagnosis/*psychology ; Disease Progression ; Educational Status ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Male ; Memory ; Memory Disorders/*diagnosis/psychology ; Middle Aged ; Neuropsychological Tests/statistics & numerical data ; Parkinson Disease/complications/diagnosis/*psychology ; Predictive Value of Tests ; Prospective Studies ; Psychiatric Status Rating Scales/statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored.

METHODS: We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation.

RESULTS: We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up.

DISCUSSION: This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI.}, } @article {pmid24786829, year = {2014}, author = {Paul, A and Gunewardena, S and Stecklein, SR and Saha, B and Parelkar, N and Danley, M and Rajendran, G and Home, P and Ray, S and Jokar, I and Vielhauer, GA and Jensen, RA and Tawfik, O and Paul, S}, title = {PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis.}, journal = {Cell death and differentiation}, volume = {21}, number = {9}, pages = {1469-1481}, pmid = {24786829}, issn = {1476-5403}, support = {HL094892/HL/NHLBI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 HD062546/HD/NICHD NIH HHS/United States ; R21 HL094892/HL/NHLBI NIH HHS/United States ; HD075233/HD/NICHD NIH HHS/United States ; HD002528/HD/NICHD NIH HHS/United States ; R21 HD075233/HD/NICHD NIH HHS/United States ; R21 HL104322/HL/NHLBI NIH HHS/United States ; HD062546/HD/NICHD NIH HHS/United States ; P30 HD002528/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Isoenzymes/genetics/*metabolism ; Lung Neoplasms/metabolism/pathology/*secondary ; Mice ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Neoplasm Transplantation ; Protein Kinase C/genetics/*metabolism ; *Signal Transduction ; Triple Negative Breast Neoplasms/*metabolism/*pathology ; }, abstract = {Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), and the patients with TNBC are often diagnosed with higher rates of recurrence and metastasis. Because of the absence of ER, PR and HER2/neu expressions, TNBC patients are insensitive to HER2-directed and endocrine therapies available for breast cancer treatment. Here, we report that expression of atypical protein kinase C isoform, PKCλ/ι, significantly increased and activated in all invasive breast cancer (invasive ductal carcinoma or IDC) subtypes including the TNBC subtype. Because of the lack of targeted therapies for TNBC, we choose to study PKCλ/ι signaling as a potential therapeutic target for TNBC. Our observations indicated that PKCλ/ι signaling is highly active during breast cancer invasive progression, and metastatic breast cancers, the advanced stages of breast cancer disease that developed more frequently in TNBC patients, are also characterized with high levels of PKCλ/ι expression and activation. Functional analysis in experimental mouse models revealed that depletion of PKCλ/ι significantly reduces TNBC growth as well as lung metastatic colonization. Furthermore, we have identified a PKCλ/ι-regulated gene signature consisting of 110 genes, which are significantly associated with indolent to invasive progression of human breast cancer and poor prognosis. Mechanistically, cytokines such as TGFβ and IL1β could activate PKCλ/ι signaling in TNBC cells and depletion of PKCλ/ι impairs NF-κB p65 (RelA) nuclear localization. We observed that cytokine-PKCλ/ι-RelA signaling axis, at least in part, involved in modulating gene expression to regulate invasion of TNBC cells. Overall, our results indicate that induction and activation of PKCλ/ι promote TNBC growth, invasion and metastasis. Thus, targeting PKCλ/ι signaling could be a therapeutic option for breast cancer, including the TNBC subtype.}, } @article {pmid24786632, year = {2014}, author = {Tessitore, A and Giordano, A and Caiazzo, G and Corbo, D and De Micco, R and Russo, A and Liguori, S and Cirillo, M and Esposito, F and Tedeschi, G}, title = {Clinical correlations of microstructural changes in progressive supranuclear palsy.}, journal = {Neurobiology of aging}, volume = {35}, number = {10}, pages = {2404-2410}, doi = {10.1016/j.neurobiolaging.2014.03.028}, pmid = {24786632}, issn = {1558-1497}, mesh = {Aged ; Cerebellum/*pathology ; Cognition ; Diffusion Magnetic Resonance Imaging ; Female ; Frontal Lobe/*pathology ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Organ Size ; Psychomotor Performance ; Supranuclear Palsy, Progressive/*pathology/*psychology ; White Matter/*pathology ; }, abstract = {In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both "intrinsic" and "extrinsic" frontal lobe dysfunction, likely related to cerebellar disconnection.}, } @article {pmid24783081, year = {2014}, author = {Kishore, J and Agarwal, R and Kohli, C and Sharma, PK and Kamat, N and Tyagi, S}, title = {Status of biomedical waste management in nursing homes of delhi, India.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {8}, number = {3}, pages = {56-58}, pmid = {24783081}, issn = {2249-782X}, abstract = {INTRODUCTION: Improper management of biomedical waste (BMW) poses a risk for health and environment. Healthcare workers have an important responsibility to properly segregate and train the staff in its disposal.

OBJECTIVE: To study the awareness, attitude and practices of health care workers in biomedical waste management and to observe the appropriateness of the same in the private nursing homes in Delhi, India.

MATERIALS AND METHODS: A cross-sectional study was conducted among private nursing homes in Delhi. In both south and east zones, 116 nursing homes were selected by random sampling method. Data was collected using a validated questionnaire of WHO. Data was analysed using SPSS software (version 16). Chi-square or fisher tests were used and accepted statistically significant if p-value was less than 0.05.

RESULTS: 41.7% of the workers in south zone and 25% in east zone had no knowledge about BMW generation (χ2=24.26, p=0.001). 57 (95%) workers in south zone and 55 (98.2%) in east zone agreed strongly that BMW management is helpful in reducing spread diseases in the community (χ2=1.22, p=0.5). On observation, it was found that 13 (21.7%) nursing homes in south zone and 15 (26.8%) in east zone did not have black bags. Practice of biomedical waste management in nursing homes in both the zones of Delhi was poor.

CONCLUSION: The study concluded that the awareness regarding biomedical waste management was not satisfactory among health care workers in private sector. There is a need of strict implementation of guidelines of BMW management.}, } @article {pmid24781343, year = {2016}, author = {Madden, NA and Macdonald, OK and Call, JA and Schomas, DA and Lee, CM and Patel, S}, title = {Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.}, journal = {American journal of clinical oncology}, volume = {39}, number = {5}, pages = {458-462}, doi = {10.1097/COC.0000000000000078}, pmid = {24781343}, issn = {1537-453X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*mortality/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*mortality/*radiotherapy/secondary/surgery ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Mastectomy/methods ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; SEER Program ; Survival Rate ; Tumor Burden ; United States/epidemiology ; }, abstract = {BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival.

MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS).

RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed.

CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.}, } @article {pmid24781337, year = {2014}, author = {Petrović, N and Mandušić, V and Dimitrijević, B and Roganović, J and Lukić, S and Todorović, L and Stanojević, B}, title = {Higher miR-21 expression in invasive breast carcinomas is associated with positive estrogen and progesterone receptor status in patients from Serbia.}, journal = {Medical oncology (Northwood, London, England)}, volume = {31}, number = {6}, pages = {977}, pmid = {24781337}, issn = {1559-131X}, mesh = {Aged ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Female ; Humans ; MicroRNAs/*genetics/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Reference Values ; Serbia ; }, abstract = {MicroRNAs play essential role in breast carcinoma progression and invasion. Our principal goals were to assess clinicopathological and prognostic correlations of microRNA-21 (miR-21) expression levels in a group of 39 Serbian breast cancer patients with invasive lobular (ILC), ductal (IDC), or mixed (ILC-IDC) breast carcinomas and in order to discover the role of miR-21 in potential novel form of stratification of the patients with different estrogen receptor (ER) and progesterone receptor (PR) status. MiR-21 expression levels were measured by stem-loop real-time RT-PCR using TaqMan technology. ER, PR, human epidermal growth factor 2 receptor (Her-2), and proliferative index (Ki-67) were evaluated by immunohistochemistry. MiR-21 levels do not vary among ILC, IDC, and ILC-IDC subgroups. MiR-21 expression levels varied significantly in the age, tumor size, Ki-67, and different grade (p = 0.030, p = 0.036, p = 0.027 and p = 0.032, respectively) subgroups. ER+ and PR+ showed higher miR-21 levels than their negative receptor status paired groups ER- and PR- with p = 0.012 and p = 0.018, respectively. MiR-21 positively correlated with ER and PR status (p = 0.018, ρ = 0.379 and p = 0.034, ρ = 0.345, respectively). Our findings suggest that miR-21 emulates transitional form of expression and that the levels of expression might be useful for stratification of the patients with different receptor status with the purpose to seek for new therapy approaches especially for the patients with the lack of response to conventional endocrine therapy.}, } @article {pmid24778809, year = {2014}, author = {Lewis, JS and Roche, C and Zhang, Y and Brusko, TM and Wasserfall, CH and Atkinson, M and Clare-Salzler, MJ and Keselowsky, BG}, title = {Combinatorial delivery of immunosuppressive factors to dendritic cells using dual-sized microspheres.}, journal = {Journal of materials chemistry. B}, volume = {2}, number = {17}, pages = {2562-2574}, pmid = {24778809}, issn = {2050-750X}, support = {R01 DK091658/DK/NIDDK NIH HHS/United States ; R21 AI094360/AI/NIAID NIH HHS/United States ; }, abstract = {Microparticulate systems are beginning to show promise for delivery of modulatory agents for immunotherapeutic applications which modulate dendritic cell (DC) functions. Co-administration of multiple factors is an emerging theme in immune modulation which may prove beneficial in this setting. Herein, we demonstrate that localized, controlled delivery of multiple factors can be accomplished through poly (lactic-co-glycolic acid) (PLGA) microparticle systems fabricated in two size classes of phagocytosable and unphagocytosable microparticles (MPs). The immunosuppressive ability of combinatorial multi-factor dual MP systems was evaluated by investigating effects on DC maturation, DC resistance to LPS-mediated maturation and proliferation of allogeneic T cells in a mixed lymphocyte reaction. Phagocytosable MPs (~2 μm) were fabricated encapsulating either rapamycin (RAPA) or all-trans retinoic acid (RA), and unphagocytosable MPs (~30 μm) were fabricated encapsulating either transforming growth factor beta-1 (TGF-β1) or interleukin-10 (IL-10). Combinations of these MP classes reduced expression of stimulatory/costimulatory molecules (MHC-II, CD80 and CD86) in comparison to iDC and soluble controls, but not necessarily to single factor MPs. Dual MP-treated DCs resisted LPS-mediated activation, in a manner driven by the single factor phagocytosable MPs used. Dendritic cells treated with dual MP systems suppressed allogeneic T cell proliferation, generally demonstrating greater suppression by combination MPs than single factor formulations, particularly for the RA/IL-10 MPs. This work demonstrates feasibility of simultaneous targeted delivery of immunomodulatory factors to cell surface receptors and intracellular locations, and indicates that a combinatorial approach can boost immunoregulatory responses for therapeutic application in autoimmunity and transplantation.}, } @article {pmid24774736, year = {2014}, author = {Isidro, A and Gonzálvez, LM and Huber, B}, title = {Mummified heart of an ancient Egyptian.}, journal = {Revista espanola de cardiologia (English ed.)}, volume = {67}, number = {5}, pages = {407}, doi = {10.1016/j.rec.2013.12.015}, pmid = {24774736}, issn = {1885-5857}, mesh = {Adult ; Egypt, Ancient ; Female ; Heart/*anatomy & histology ; History, Ancient ; Humans ; }, } @article {pmid24772919, year = {2014}, author = {Capobianco, G and Simbula, L and Soro, D and Meloni, F and Cossu-Rocca, P and Dessole, S and Ambrosini, G and Cherchi, PL and Meloni, GB}, title = {Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.}, journal = {European journal of gynaecological oncology}, volume = {35}, number = {2}, pages = {157-162}, pmid = {24772919}, issn = {0392-2936}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma in Situ/*diagnosis/surgery ; Carcinoma, Lobular/*diagnosis/surgery ; Female ; Humans ; Mammography ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; *Neoplasm Recurrence, Local ; Retrospective Studies ; Treatment Outcome ; Ultrasonography, Mammary ; Young Adult ; }, abstract = {PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS).

MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up.

RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months.

CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.}, } @article {pmid24768572, year = {2014}, author = {Purushotham, A and Shamil, E and Cariati, M and Agbaje, O and Muhidin, A and Gillett, C and Mera, A and Sivanadiyan, K and Harries, M and Sullivan, R and Pinder, SE and Garmo, H and Holmberg, L}, title = {Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {10}, pages = {1697-1705}, doi = {10.1016/j.ejca.2014.04.002}, pmid = {24768572}, issn = {1879-0852}, mesh = {Adult ; Age Factors ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/mortality/*secondary/therapy ; Breast Neoplasms/chemistry/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary/therapy ; Carcinoma, Lobular/chemistry/mortality/*secondary/therapy ; Disease-Free Survival ; ErbB Receptors/analysis ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Proportional Hazards Models ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Registries ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; }, abstract = {INTRODUCTION: Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood.

METHODS: Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006.

RESULTS: Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis.

CONCLUSION: These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer.}, } @article {pmid24766990, year = {2014}, author = {Benezet-Mazuecos, J and Rubio, JM and Farré, J}, title = {Atrial fibrillation in cardiac implantable electronic devices and the duck test.}, journal = {American heart journal}, volume = {167}, number = {5}, pages = {e13}, doi = {10.1016/j.ahj.2014.02.004}, pmid = {24766990}, issn = {1097-6744}, mesh = {Atrial Fibrillation/*diagnosis ; Humans ; Monitoring, Ambulatory/*methods ; }, } @article {pmid24762482, year = {2014}, author = {Singh, R and Gupta, S and Pawar, SB and Pawar, RS and Gandham, SV and Prabhudesai, S}, title = {Evaluation of ER, PR and HER-2 receptor expression in breast cancer patients presenting to a semi urban cancer centre in Western India.}, journal = {Journal of cancer research and therapeutics}, volume = {10}, number = {1}, pages = {26-28}, doi = {10.4103/0973-1482.131348}, pmid = {24762482}, issn = {1998-4138}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/*metabolism ; Cancer Care Facilities ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; India ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; Risk Factors ; Urban Health Services ; Young Adult ; }, abstract = {BACKGROUND: Hormone receptor expression has been reported to be low in breast cancer patients from developing countries. The pattern of receptor expression from urban and rural areas is not well studied.

MATERIALS AND METHODS: This is a retrospective analysis of 206 consecutive breast cancer patients presenting to a semi urban cancer centre from 2009-2010. The demographic and clinical variables included age, residential area (rural, semi urban, or urban), menopausal status, and clinical stage. The pathological variables included tumor type, the presence of ductal carcinoma in situ, lymphovascular invasion, and expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptors by immunohistochemical (IHC) analysis.

RESULTS: The majority of patients were postmenopausal with the median age of 50 years. Invasive ductal carcinoma was the most common subtype (94%). The ER status was available in 101 (49.3%), PR in 99 (48.0%), and HER2 in 82 (39.8%) cases. In patients in whom this data were available, ER was positive in 44.6%, PR in 40.4%, and HER2 in 34.2%. Out of the 82 patients in whom data on all three receptors were available, 34.1% patients had triple negative tumors. Analysis of our data showed a trend toward increasing ER and PR expression with age but this was not statistically significant. The average age of menopause was between 40-50 years of age.

CONCLUSION: This report is an important documentation of the pathological characteristics in a predominantly rural/semi urban population of Indian breast cancer patients. Further studies from other centers with a similar background are required to confirm these results.}, } @article {pmid24759678, year = {2014}, author = {Ramos, CS and Gonçalves, AS and Marinho, LC and Gomes Avelino, MA and Saddi, VA and Lopes, AC and Simões, RT and Wastowski, IJ}, title = {Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma.}, journal = {Human immunology}, volume = {75}, number = {7}, pages = {667-672}, doi = {10.1016/j.humimm.2014.04.005}, pmid = {24759678}, issn = {1879-1166}, mesh = {Alleles ; Breast Neoplasms/*genetics/immunology/mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/immunology/mortality/pathology ; Case-Control Studies ; Female ; Gene Expression ; Gene Frequency ; HLA-G Antigens/*genetics/immunology ; Humans ; *INDEL Mutation ; Lymph Nodes/immunology/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Survival Analysis ; }, abstract = {The human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule predominantly expressed in trophoblastic placental cells to protect the fetus during pregnancy. However, evidence has shown that this molecule may be implicated in the immune escape mechanism of tumor cells. Thus, the aim of this study was to evaluate the frequency of 14-bp insertion/deletion HLA-G polymorphism, as well as the expression of this molecule in patients with invasive breast ductal carcinoma (IDC). A significant association between the expression of HLA-G and the presence of metastasis in lymph nodes (p=0.01) was observed and the expression of HLA-G was significantly higher in patients with shorter survival time (p=0.03). The analysis suggests that the polymorphism observed in patients with IDC may be inducing a higher expression of the HLA-G molecule, which may possibly contribute to shorter survival time and a worse clinical prognosis for such patients.}, } @article {pmid24756760, year = {2014}, author = {Do, SI and Ko, E and Kang, SY and Lee, JE and Nam, SJ and Cho, EY and Kim, DH}, title = {Aberrant DNA methylation of integrin α4 in human breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {7}, pages = {7079-7084}, pmid = {24756760}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; CpG Islands/*genetics ; DNA Methylation/*genetics ; Female ; Humans ; Integrin alpha4/*genetics ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Prognosis ; Promoter Regions, Genetic ; Receptor, ErbB-2/metabolism ; Signal Transduction ; }, abstract = {Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.}, } @article {pmid24752982, year = {2015}, author = {Nakash, O and Langer, B and Nagar, M and Shoham, S and Lurie, I and Davidovitch, N}, title = {Exposure to Traumatic Experiences Among Asylum Seekers from Eritrea and Sudan During Migration to Israel.}, journal = {Journal of immigrant and minority health}, volume = {17}, number = {4}, pages = {1280-1286}, pmid = {24752982}, issn = {1557-1920}, mesh = {Adolescent ; Adult ; *Emigration and Immigration/statistics & numerical data ; Eritrea/ethnology ; Female ; Humans ; Israel/epidemiology ; Male ; Sex Factors ; Sudan/ethnology ; Violence/*statistics & numerical data ; Young Adult ; }, abstract = {Little is known about the experiences of displaced individuals en route to destination countries. We investigated the reported prevalence of exposure to traumatic experiences during migration among a consecutive sample of adult asylum seekers (n = 895 Eritrean, n = 149 Sudanese) who sought health services in the Physicians for Human Rights Open-Clinic in Israel. Percentage of Eritrean and Sudanese men and women who reported witnessing violence (Eritrea: men: 41.3 %, women: 29.3 %; Sudan: men: 16.8 %, women: 22.2 %) and/or being a victim of violence (Eritrea: men: 56.0 %, Women: 34.9 %; Sudan: men: 51.9 % women: 44.4 %) during migration varied by gender and country of origin. Findings highlight the need for a well-coordinated international cooperation to document and prevent these transgressions.}, } @article {pmid24748104, year = {2014}, author = {Ruan, X and Liu, H and Boardman, L and Kocher, JP}, title = {Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal carcinoma distant normal tissue highlights arm specific enrichment and expansion across tumor stages.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e95783}, pmid = {24748104}, issn = {1932-6203}, support = {P30 CA015083/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Chromosome Fragile Sites ; Chromosome Mapping ; *Chromosomes, Human ; Female ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; *Loss of Heterozygosity ; Neoplasm Staging ; }, abstract = {Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the overall extent of LOH in normal tissue and their significance to tumorigenesis remain unknown, as existing studies are largely based on selected microsatellite markers. Here we present the first autosome-wide study of LOH in IDC and distant normal tissue using informative loci deduced from SNP array-based and sequencing-based techniques. We show a consistently high LOH concurrence rate in IDC (mean = 24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33) histologically normal tissue contains genomic instability that can be a potential marker of increased IDC risk. Concurrent LOH is more frequent in fragile site related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm level shows distant normal tissue has low level but non-random enrichment of LOH (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r = 0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific LOH enrichment was independently observed in tumor samples from 548 IDC patients when stratified by tumor size based T stages. Fine LOH structure from sequencing data indicates LOH in low order tissues non-randomly overlap (∼67%) with LOH that usually has longer tract length (the length of genomic region affected by LOH) in high order tissues. The consistent observations from multiple datasets suggest progressive LOH in the development of IDC potentially through arm-specific pile up effect with discernible signature in normal tissue. Our finding also suggests that LOH detected in IDC by comparing to paired adjacent or distant normal tissue are more likely underestimated.}, } @article {pmid24744949, year = {2014}, author = {Santivasi, WL and Routt, MM and Terando, AM}, title = {Idiopathic thrombocytopenic purpura after mastectomy and axillary lymph node dissection.}, journal = {Case reports in surgery}, volume = {2014}, number = {}, pages = {316064}, pmid = {24744949}, issn = {2090-6900}, abstract = {First described in 1916, idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease resulting in the destruction of platelets. Here, we present a case of an 85-year-old patient diagnosed with invasive ductal carcinoma of the breast whose surgical treatment was complicated postoperatively by acute-onset thrombocytopenia with a resultant hematoma at the operative site. Diagnostic Workup revealed no clear etiology for the thrombocytopenia; therefore, a presumptive diagnosis of idiopathic thrombocytopenic purpura was made. Previous literature has associated the development of idiopathic thrombocytopenic purpura with breast cancer. However, to the authors' knowledge, there are no reported cases of ITP presenting immediately following surgical intervention for breast cancer in the absence of other etiologic factors.}, } @article {pmid24744804, year = {2014}, author = {Hahm, MH and Kim, HJ and Shin, KM and Cho, SH and Park, JY and Jung, JH and Jeong, JY and Bae, JH}, title = {Concurrent invasive ductal carcinoma of the breast and malignant follicular lymphoma, initially suspected to be metastatic breast cancer: a case report.}, journal = {Journal of breast cancer}, volume = {17}, number = {1}, pages = {91-97}, pmid = {24744804}, issn = {1738-6756}, abstract = {This report describes a case of a 40-year-old female patient with concurrent invasive ductal carcinoma of the breast and malignant follicular lymphoma, initially suspected to be metastatic breast cancer. During the initial evaluation of invasive ductal carcinoma of right breast, multiple lymphadenopathies were noted throughout the body on ultrasonography and positron emission tomography/computed tomography images. Clinically, metastatic breast cancer was suggested, and the patient was administered chemotherapy, including hormonal therapy. The breast cancer improved slightly, but the lymphadenopathies progressed and excisional biopsy of a cervical lymph node revealed malignant follicular lymphoma.}, } @article {pmid24744792, year = {2014}, author = {Kim, S and Lee, A and Lim, W and Park, S and Cho, MS and Koo, H and Moon, BI and Sung, SH}, title = {Zonal difference and prognostic significance of foxp3 regulatory T cell infiltration in breast cancer.}, journal = {Journal of breast cancer}, volume = {17}, number = {1}, pages = {8-17}, pmid = {24744792}, issn = {1738-6756}, abstract = {PURPOSE: Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer.

METHODS: Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome.

RESULTS: The tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of ≥14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased.

CONCLUSION: The infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.}, } @article {pmid24743366, year = {2014}, author = {Inafuku, K and Inari, H and Goto, N and Kawamoto, M and Hatori, S and Tanabe, H and Masuda, M}, title = {[A case of postmenopausal breast cancer becoming HER2 positive after neoadjuvant hormone therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {41}, number = {4}, pages = {487-489}, pmid = {24743366}, issn = {0385-0684}, mesh = {Aged ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biopsy ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Female ; Humans ; Mammography ; *Neoadjuvant Therapy ; Neoplasm Staging ; Nitriles/*therapeutic use ; Postmenopause ; Receptor, ErbB-2/*analysis ; Triazoles/*therapeutic use ; }, abstract = {A 75-year-old woman presented to a local doctor with a lump in the right breast. On physical examination, a tumor measuring 24mm was palpable in the BD area of her right breast. Mammography showed category 5 disease, and ultrasonography revealed a tumor measuring 24×16 mm. A mammotome biopsy provided a diagnosis of invasive ductal carcinoma of the breast(ER 7/PgR 4/HER2 1+), and the tumor was classified as stage IIA(T2N0M0)according to the UICC-TNM classification. She was recommended surgery but she rejected this option and underwent hormone therapy with anastrozole (1mg/day). One year and 8months after beginning the treatment, ultrasonography showed the tumor to measure 7.0×5.7 mm, and hormone therapy resulted in a partial response(PR). The patient hoped to undergo an operation, so she was referred to our hospital, and a right partial mastectomy and sentinel node biopsy was performed. A histopathological exami- nation indicated scirrhous carcinoma, 18mm, nuclear grade 1, f, ly1, v0, n0, ER 3/PgR 3/HER2 3+. The curative effect was grade 1a. The tumor had become HER2 positive, so the patient was then administered radiotherapy and trastuzumab and anastrozole as adjuvant therapy. Herein, we report our experience with a case of breast cancer that only became HER2 positive after hormone therapy, and also provide some bibliographic comments on this occurrence.}, } @article {pmid24743323, year = {2014}, author = {Sawyer, E and Roylance, R and Petridis, C and Brook, MN and Nowinski, S and Papouli, E and Fletcher, O and Pinder, S and Hanby, A and Kohut, K and Gorman, P and Caneppele, M and Peto, J and Dos Santos Silva, I and Johnson, N and Swann, R and Dwek, M and Perkins, KA and Gillett, C and Houlston, R and Ross, G and De Ieso, P and Southey, MC and Hopper, JL and Provenzano, E and Apicella, C and Wesseling, J and Cornelissen, S and Keeman, R and Fasching, PA and Jud, SM and Ekici, AB and Beckmann, MW and Kerin, MJ and Marme, F and Schneeweiss, A and Sohn, C and Burwinkel, B and Guénel, P and Truong, T and Laurent-Puig, P and Kerbrat, P and Bojesen, SE and Nordestgaard, BG and Nielsen, SF and Flyger, H and Milne, RL and Perez, JI and Menéndez, P and Benitez, J and Brenner, H and Dieffenbach, AK and Arndt, V and Stegmaier, C and Meindl, A and Lichtner, P and Schmutzler, RK and Lochmann, M and Brauch, H and Fischer, HP and Ko, YD and , and Nevanlinna, H and Muranen, TA and Aittomäki, K and Blomqvist, C and Bogdanova, NV and Dörk, T and Lindblom, A and Margolin, S and Mannermaa, A and Kataja, V and Kosma, VM and Hartikainen, JM and Chenevix-Trench, G and , and Lambrechts, D and Weltens, C and Van Limbergen, E and Hatse, S and Chang-Claude, J and Rudolph, A and Seibold, P and Flesch-Janys, D and Radice, P and Peterlongo, P and Bonanni, B and Volorio, S and Giles, GG and Severi, G and Baglietto, L and McLean, CA and Haiman, CA and Henderson, BE and Schumacher, F and Le Marchand, L and Simard, J and Goldberg, MS and Labrèche, F and Dumont, M and Kristensen, V and Winqvist, R and Pylkäs, K and Jukkola-Vuorinen, A and Kauppila, S and Andrulis, IL and Knight, JA and Glendon, G and Mulligan, AM and Devillee, P and Tollenaar, RA and Seynaeve, CM and Kriege, M and Figueroa, J and Chanock, SJ and Sherman, ME and Hooning, MJ and Hollestelle, A and van den Ouweland, AM and van Deurzen, CH and Li, J and Czene, K and Humphreys, K and Cox, A and Cross, SS and Reed, MW and Shah, M and Jakubowska, A and Lubinski, J and Jaworska-Bieniek, K and Durda, K and Swerdlow, A and Ashworth, A and Orr, N and Schoemaker, M and Couch, FJ and Hallberg, E and González-Neira, A and Pita, G and Alonso, MR and Tessier, DC and Vincent, D and Bacot, F and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Dunning, AM and Hall, P and Easton, D and Pharoah, P and Schmidt, MK and Tomlinson, I and Garcia-Closas, M}, title = {Genetic predisposition to in situ and invasive lobular carcinoma of the breast.}, journal = {PLoS genetics}, volume = {10}, number = {4}, pages = {e1004285}, pmid = {24743323}, issn = {1553-7404}, support = {U01 CA69417/CA/NCI NIH HHS/United States ; UM1 CA164920/CA/NCI NIH HHS/United States ; U01 CA069467/CA/NCI NIH HHS/United States ; 2010NOVPR61/BCN_/Breast Cancer Now/United Kingdom ; R01 CA128978/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; 090532/WT_/Wellcome Trust/United Kingdom ; R01 CA132839/CA/NCI NIH HHS/United States ; 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; CA098758/CA/NCI NIH HHS/United States ; U01 CA069417/CA/NCI NIH HHS/United States ; CA54281/CA/NCI NIH HHS/United States ; U01 CA069638/CA/NCI NIH HHS/United States ; 10124/CRUK_/Cancer Research UK/United Kingdom ; CA63464/CA/NCI NIH HHS/United States ; C490/A10124/CRUK_/Cancer Research UK/United Kingdom ; C1287/A12014/CRUK_/Cancer Research UK/United Kingdom ; R01 CA063464/CA/NCI NIH HHS/United States ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA69638/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; U01 CA098758/CA/NCI NIH HHS/United States ; CA132839/CA/NCI NIH HHS/United States ; C1287/A10118/CRUK_/Cancer Research UK/United Kingdom ; U01 CA69467/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma in Situ/*genetics ; Carcinoma, Lobular/*genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.}, } @article {pmid24743129, year = {2014}, author = {Gudadze, M and Kankava, Q and Mariamidze, A and Burkadze, G}, title = {Features of CD44+/CD24-low phenotypic cell distribution in relation to predictive markers and molecular subtypes of invasive ductal carcinoma of the breast.}, journal = {Georgian medical news}, volume = {}, number = {228}, pages = {81-87}, pmid = {24743129}, issn = {1512-0112}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/metabolism/*pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Middle Aged ; Neoplastic Stem Cells/metabolism/pathology ; Phenotype ; Prognosis ; Young Adult ; }, abstract = {Breast cancer is the most widespread pathology among women. Despite the current progresses in research and treatment of metastatic breast cancer, mortality caused by this disease is still high, because above mentioned therapy is limited due to existence of cells resistant to therapy . Cancer stem cells are the only cells with ability of unlimited proliferative activity and cancerous potential, thus, they participate in the growth, progression and dissemination of cancer. Cancer stem cells are resistant to various forms of therapy, including chemotherapy and radiotherapy . Results of examination showed that 50% of all cases are positive on so called markers of stem cells, thus 45% of cases are negative. CD44+/CD24-low cases (cases that reveal stem cell-phenotype) in the group of invasive ductal carcinoma of Luminal A molecular subtype are almost as many as CD44+/CD24+ and CD44-/CD24+ phenotype cancers. In this group non-stem phenotype cases are 65%, so 5 times more than stem cell phenotype cancers. 1324 postoperative breast materials studied through 2008-2012 at the laboratory of "Pathgeo-Union of Pathologists" LTD and Academician N. Kipshidze Central University Clinic were used as test materials and specimens from 393 patients with invasive ductal carcinoma were selected. CD44/CD24 markers' expression in phenotypically different cancers and clinic-pathologic parameters as well as various biological features was conducted by the Pearson's correlation analysis and using X2 test. Statistical analysis of obtained numeral data was held using SPSS V.19.0 program. Confidence interval of 95% was considered statistically significant. Stem cell phenotype positive cases are with the highest percentage represented in Luminal B and basal-like molecular subgroup that to our minds is associated with their aggressive behavior and resistance to chemotherapy. Relatively good prognosis and response to chemotherapy of Luminal A molecular subtype cancers are to be stipulated by lower percentage of cases with stem cells phenotype. With regard to the dimension of cancer the analysis of stem cell phenotype cancers showed that frequency of stem cell phenotype (CD44+/CD24-low) dramatically increases from T1 to T4 cancers. High density of stem cell phenotype cancers in cancers with metastatic lymphatic nodes proves that presence of mentioned phenotype plays a role in progression and dissemination. On the one hand, little amount of stem cells phenotype cancers (CD44+/CD24-low), on the other hand absence of negative cases for markers of stem cell in Her2 subtype makes us consider that come phenotype, close to stem-cell phenotype, plays the leading role in Her2 positive cases.}, } @article {pmid24742110, year = {2014}, author = {Xu, Y and Ming, J and Zhou, Y and Qi, X and Fan, L and Jiang, J}, title = {Mammotome-assisted endoscopic breast-conserving surgery: a novel technique for early-stage breast cancer.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {99}, pmid = {24742110}, issn = {1477-7819}, mesh = {Adult ; Axilla ; Biopsy, Needle ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; *Endoscopy ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/diagnostic imaging/pathology/*surgery ; Neoplasm Staging ; Prognosis ; Ultrasonography, Interventional ; Vacuum ; }, abstract = {BACKGROUND: Because of its minimally invasive and highly accurate nature, the use of Mammotome, a vacuum-assisted breast biopsy device has proven beneficial to the treatment of benign breast lesions. Taking advantage of endoscopic and Mammotome techniques together, we utilized the Mammotome device for therapeutic excision of malignant lesions in breast-conserving surgery (BCS).

METHODS: Between December 2009 and January 2010, two patients with early breast cancer received Mammotome-assisted endoscopic BCSs. Under ultrasound monitoring, the Mammotome system dissected the surrounding tissue and freed the tumor en bloc leaving negative margins; endoscopic axillary lymph node dissection then followed.

RESULTS: The operation time was less than 180 minutes and the mean blood loss was 60 ml. The post-operative pathology report confirmed two patients to have invasive ductal carcinoma, one without axillary lymph nodes metastasis (0/11) and the other with one lymph node metastasis (1/21). No adverse events were noted. During a mean follow-up of 26.5 months, no evidence of recurrence or metastasis was found. The patients were satisfied with the cosmetic results.

CONCLUSIONS: Mammotome-assisted endoscopic surgery appears to be a valuable option for early breast cancer. The long-term therapeutic effect remains to be confirmed.}, } @article {pmid24732679, year = {2014}, author = {Gallivanone, F and Canevari, C and Sassi, I and Zuber, V and Marassi, A and Gianolli, L and Picchio, M and Messa, C and Gilardi, MC and Castiglioni, I}, title = {Partial volume corrected 18F-FDG PET mean standardized uptake value correlates with prognostic factors in breast cancer.}, journal = {The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...}, volume = {58}, number = {4}, pages = {424-439}, pmid = {24732679}, issn = {1824-4785}, mesh = {Adult ; Aged ; Aged, 80 and over ; Body Weight ; Breast Neoplasms/*diagnostic imaging ; Cluster Analysis ; Data Interpretation, Statistical ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Mammography/methods ; Middle Aged ; Models, Statistical ; Multimodal Imaging ; Multivariate Analysis ; Positron-Emission Tomography/*methods ; Prognosis ; ROC Curve ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Regression Analysis ; Tomography, X-Ray Computed/methods ; }, abstract = {AIM: The aim of this paper was to assess the prognostic role of pretherapy partial volume corrected (PVC) 18F-fluorodeoxyglucose mean standardized uptake value (SUV) in breast cancer (BC).

METHODS: Forty oncological patients, BC diagnosed by biopsy, with breast tumor mass diameter >1 cm measured to the mammography, designed for surgical intervention, underwent a pretherapy semi-quantitative 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) whole-body study for tumor staging. Mean Body-Weight Standardized Uptake Value with Correction for Partial Volume effect (PVC- SUVBW-mean) was calculated in all mammary detected lesions. Excised tissues from primitive BC were sectioned and classified according to the WHO guidelines, evaluating biological features. Univariate (Mann-Withney/Kruskal-Wallis) and multivariate (linear regression, hierarchical clustering) statistical tests were performed between PVC-SUVBW-mean and biological indexes. ROC analysis was performed. PVC-SUVBW-mean thresholds were derived allowing to distinguish groups of BC patients with different biological characteristics. Specificity and Sensitivity were also calculated.

RESULTS: Statistical and multiple correlations between pretherapy 18F-FDG PET PVC-SUVBW-mean and histological type, grade, ER/PgR hormone receptors and Mib-1 cellular proliferation index were found. In our samples, PVC-SUVBW-mean <≈4 g/cc was found correlated to BC patients with Invasive Lobular Carcinoma (ILC) or well differentiated Invasive Ductal Carcinoma (IDC), a positive expression of ER and PgR and a negative expression of MiB-1, while PVC-SUVBW-mean >≈7.00 is associated to BC patients with moderately and poorly differentiated IDC, negative expression of ER and PgR and a positive expression of MiB-1.

CONCLUSION: Pretherapy PVC 18F-FDG PET PVC-SUVBW-mean measurement correlates with prognostic factors in BC and could be used to stratify patients before intervention.}, } @article {pmid24725754, year = {2014}, author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Longo, K and Amboni, M and Santangelo, G and Spina, E and De Rosa, A and De Michele, G and Santoro, L and Barone, P and Pellecchia, MT}, title = {Is serum uric acid related to non-motor symptoms in de-novo Parkinson's disease patients?.}, journal = {Parkinsonism & related disorders}, volume = {20}, number = {7}, pages = {772-775}, doi = {10.1016/j.parkreldis.2014.03.016}, pmid = {24725754}, issn = {1873-5126}, mesh = {Adult ; Aged ; Biomarkers/blood ; Cardiovascular Diseases/blood/complications/diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mental Disorders/blood/complications/diagnosis ; Middle Aged ; Parkinson Disease/*blood/complications/*diagnosis ; Pilot Projects ; Uric Acid/*blood ; }, abstract = {BACKGROUND: Low serum uric acid (UA) has been consistently shown to be associated with increased risk of Parkinson's disease (PD), and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) in de novo PD.

METHODS: Serum UA was measured in consecutively recruited, early drug-naïve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and was subsequently adjusted for age, gender, disease duration UPDRS part III, H&Y scale and MMSE.

RESULTS: Eighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p = 0.004), Cardiovascular (0.009) and Sleep (p = 0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p = 0.001; Adjusted R-squared = 0.319).

DISCUSSION: The present study investigated, for the first time, the relationship between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.}, } @article {pmid24723231, year = {2014}, author = {Jiang, J and Chen, YQ and Xu, YZ and Chen, ML and Zhu, YK and Guan, WB and Wang, XJ}, title = {Correlation between three-dimensional ultrasound features and pathological prognostic factors in breast cancer.}, journal = {European radiology}, volume = {24}, number = {6}, pages = {1186-1196}, pmid = {24723231}, issn = {1432-1084}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Middle Aged ; Neovascularization, Pathologic/diagnostic imaging/metabolism/pathology ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Ultrasonography ; }, abstract = {OBJECTIVES: To investigate the correlation of three-dimensional (3D) ultrasound features with prognostic factors in invasive ductal carcinoma.

METHODS: Surgical resection specimens of 85 invasive ductal carcinomas of 85 women who had undergone 3D ultrasound were included. Morphology features and vascularization perfusion on 3D ultrasound were evaluated. Pathologic prognostic factors, including tumour size, histological grade, lymph node status, oestrogen and progesterone receptor status (ER, PR), c-erbB-2 and p53 expression, and microvessel density (MVD) were determined. Correlations of 3D ultrasound features and prognostic factors were analysed.

RESULTS: The retraction pattern in the coronal plane had a significant value as an independent predictor of a small tumour size (P = 0.014), a lower histological grade (P = 0.009) and positive ER or PR expression status (P = 0.001, 0.044). The retraction pattern with a hyperechoic ring only existed in low-grade and ER-positive tumours. The presence of the hyperechoic ring strengthened the ability of the retraction pattern to predict a good prognosis of breast cancer. The increased intra-tumour vascularization index (VI, the mean tumour vascularity) reflected a higher histological grade (P = 0.025) and had a positive correlation with MVD (r = 0.530, P = 0.001).

CONCLUSIONS: The retraction pattern and histogram indices of VI provided by 3D ultrasound may be useful in predicting prognostic information about breast cancer.

KEY POINTS: Three-dimensional ultrasound can potentially provide prognostic evaluation of breast cancer. The retraction pattern and hyperechoic ring in the coronal plane suggest good prognosis. The increased intra-tumour vascularization index reflects a higher histological grade. The intra-tumour vascularization index is positively correlated with microvessel density.}, } @article {pmid24721660, year = {2014}, author = {Angarita, FA and Nadler, A and Zerhouni, S and Escallon, J}, title = {Perioperative measures to optimize margin clearance in breast conserving surgery.}, journal = {Surgical oncology}, volume = {23}, number = {2}, pages = {81-91}, doi = {10.1016/j.suronc.2014.03.002}, pmid = {24721660}, issn = {1879-3320}, mesh = {Breast Neoplasms/*pathology/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; *Perioperative Care ; }, abstract = {Margin status is one of the most important determinants of local recurrence following breast conserving surgery. The fact that up to 60% of patients undergoing breast conserving surgery require re-excision highlights the importance of optimizing margin clearance. In this review we summarize the following perioperative measures that aim to enhance margin clearance: (1) patient risk stratification, specifically risk factors and nomograms, (2) preoperative imaging, (3) intraoperative techniques including wire-guided localization, radioguided surgery, intraoperative ultrasound-guided resection, intraoperative specimen radiography, standardized cavity shaving, and ink-directed focal re-excision; (4) and intraoperative pathology assessment techniques, namely frozen section analysis and imprint cytology. Novel surgical techniques as well as emerging technologies are also reviewed. Effective treatment requires accurate preoperative planning, developing and implementing a consistent definition of margin clearance, and using tools that provide detailed real-time intraoperative information on margin status.}, } @article {pmid24719331, year = {2014}, author = {Al-Huseini, LM and Aw Yeang, HX and Hamdam, JM and Sethu, S and Alhumeed, N and Wong, W and Sathish, JG}, title = {Heme oxygenase-1 regulates dendritic cell function through modulation of p38 MAPK-CREB/ATF1 signaling.}, journal = {The Journal of biological chemistry}, volume = {289}, number = {23}, pages = {16442-16451}, pmid = {24719331}, issn = {1083-351X}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Activating Transcription Factor 1/*metabolism ; Animals ; Cyclic AMP Response Element-Binding Protein/*metabolism ; Dendritic Cells/cytology/*metabolism ; Heme Oxygenase-1/*metabolism ; Mice ; Mice, Transgenic ; *Signal Transduction ; p38 Mitogen-Activated Protein Kinases/*metabolism ; }, abstract = {Dendritic cells (DCs) are critical for the initiation of immune responses including activation of CD8 T cells. Intracellular reactive oxygen species (ROS) levels influence DC maturation and function. Intracellular heme, a product of catabolism of heme-containing metalloproteins, is a key inducer of ROS. Intracellular heme levels are regulated by heme oxygenase-1 (HO-1), which catalyzes the degradation of heme. Heme oxygenase-1 has been implicated in regulating DC maturation; however, its role in other DC functions is unclear. Furthermore, the signaling pathways modulated by HO-1 in DCs are unknown. In this study, we demonstrate that inhibition of HO-1 activity in murine bone marrow-derived immature DCs (iDCs) resulted in DCs with raised intracellular ROS levels, a mature phenotype, impaired phagocytic and endocytic function, and increased capacity to stimulate antigen-specific CD8 T cells. Interestingly, our results reveal that the increased ROS levels following HO-1 inhibition did not underlie the changes in phenotype and functions observed in these iDCs. Importantly, we show that the p38 mitogen-activated protein kinase (p38 MAPK), cAMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1) pathway is involved in the mediation of the phenotypic and functional changes arising from HO-1 inhibition. Furthermore, up-regulation of HO-1 activity rendered iDCs refractory to lipopolysaccharide-induced activation of p38 MAPK-CREB/ATF1 pathway and DC maturation. Finally, we demonstrate that treatment of iDC with the HO-1 substrate, heme, recapitulates the effects that result from HO-1 inhibition. Based on these results, we conclude that HO-1 regulates DC maturation and function by modulating the p38 MAPK-CREB/ATF1 signaling axis.}, } @article {pmid24716784, year = {2014}, author = {Fujii, T and Yajima, R and Morita, H and Yamaguchi, S and Tsutsumi, S and Asao, T and Kuwano, H}, title = {Adenoma of the nipple projecting out of the nipple: curative resection without excision of the nipple.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {91}, pmid = {24716784}, issn = {1477-7819}, mesh = {Adenoma/pathology/*surgery ; Adult ; Breast Neoplasms/pathology/*surgery ; Female ; Humans ; Nipples/pathology/*surgery ; *Organ Sparing Treatments ; Prognosis ; }, abstract = {BACKGROUND: Adenoma of the nipple is a rare breast tumor that is often mistaken clinically for Paget's disease and misinterpreted pathologically as invasive ductal carcinoma.

CASE REPORT: We report herein a distinctive case of adenoma of the nipple projecting out of the nipple. In the current case, we were able to perform curative resection through a periareolar incision similar to a microdochectomy without excision of the nipple. The diagnosis of adenoma of the nipple was confirmed histopathologically.

CONCLUSION: Although the tumor was found on top of the nipple, curative tumor resection without excision of the nipple was possible and the nipple was completely preserved. Adenoma of the nipple is a benign tumor, and thus the diagnosis of adenoma of the nipple must be confirmed so that unnecessary surgery can be avoided.}, } @article {pmid24715382, year = {2014}, author = {McNamara, KM and Yoda, T and Nurani, AM and Shibahara, Y and Miki, Y and Wang, L and Nakamura, Y and Suzuki, K and Yang, Y and Abe, E and Hirakawa, H and Suzuki, T and Nemoto, N and Miyashita, M and Tamaki, K and Ishida, T and Brown, KA and Ohuchi, N and Sasano, H}, title = {Androgenic pathways in the progression of triple-negative breast carcinoma: a comparison between aggressive and non-aggressive subtypes.}, journal = {Breast cancer research and treatment}, volume = {145}, number = {2}, pages = {281-293}, doi = {10.1007/s10549-014-2942-6}, pmid = {24715382}, issn = {1573-7217}, mesh = {3-Hydroxysteroid Dehydrogenases/genetics/metabolism ; Aldo-Keto Reductase Family 1 Member C3 ; Androgens/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cholestenone 5 alpha-Reductase/genetics/metabolism ; Dihydrotestosterone/pharmacology ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Receptors, Androgen/metabolism ; Triple Negative Breast Neoplasms/drug therapy/*metabolism/*pathology ; }, abstract = {One of the active intracellular pathways/networks in triple-negative breast carcinoma (TNBC) is that of the androgen receptor (AR). In this study, we examined AR and androgen-metabolising enzyme immunoreactivity in subcategories of TNBC to further elucidate the roles of androgenic pathways in TNBC. We utilised formalin-fixed paraffin-embedded breast cancer samples from ductal carcinoma in situ (DCIS) and invasive ductal carcinoma patient cohorts. We then used immunohistochemistry to classify these samples into basal-like and non-basal samples and to assess interactions between AR, androgen-metabolising enzymes and proliferation. To further substantiate our hypothesis and provide mechanistic insights, we also looked at the expression and regulation of these factors in publically available microarray data and in a panel of TNBC AR-positive cell lines. DCIS was associated with higher levels of AR and enzymes (p < 0.02), although a similar difference was not noticed in basal and non-basal samples. AR and enzymes were correlated in all states. In TNBC cell lines (MDA-MD-453, MFM-223 and SUM185-PE), we found that DHT treatment up-regulated 5αR1 and 17βHSD5 suggesting a mechanistic explanation for the correlations observed in the histological samples. Publicly available microarray data in TNBC cases suggested similar patterns to those observed in histological samples. In the majority of settings, including publically available microarray data, an inverse association between AR and proliferation was detected. These findings suggest that decreases in AR and androgen-metabolising enzymes may be involved in the increased biological aggressiveness in TNBC development.}, } @article {pmid24713490, year = {2014}, author = {Ruiz Santiago, F and Pozuelo Calvo, R and Almansa López, J and Guzmán Álvarez, L and Castellano García, MDM}, title = {T2 mapping in patellar chondromalacia.}, journal = {European journal of radiology}, volume = {83}, number = {6}, pages = {984-988}, doi = {10.1016/j.ejrad.2014.03.007}, pmid = {24713490}, issn = {1872-7727}, mesh = {Adolescent ; Adult ; *Algorithms ; Arthralgia/*diagnosis/*etiology ; Chondromalacia Patellae/*complications/*pathology ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia.

METHODS: This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16-45 years). MRI of 97 knees were performed in these patients at 1.5T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet-proximal-lateral (EPL), external facet-proximal-central (EPC), internal facet-proximal-central (IPC), internal facet-proximal-medial (IPM), 4 in the middle section (external facet-middle-lateral (EML), external facet-middle-central (EMC), internal facet-middle-central (IMC), internal facet-middle-medial (IMM) and 4 distal (external facet-distal-lateral (EDL), external facet-distal-central (EDC), internal facet-distal-central (IDC), internal facet-distal-medial (IDM).

RESULTS: T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p<0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p<0.05).

CONCLUSIONS: Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased.}, } @article {pmid24713245, year = {2014}, author = {Bi, R and Cheng, Y and Yu, B and Shui, R and Yang, W and Xu, X}, title = {[Clinicopathologic features of cystic hypersecretory lesion of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {43}, number = {1}, pages = {25-29}, pmid = {24713245}, issn = {0529-5807}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/surgery ; Epithelium/pathology ; Female ; Fibrocystic Breast Disease/metabolism/*pathology/surgery ; Humans ; Hyperplasia ; Immunohistochemistry ; Keratin-14/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Lymphatic Metastasis ; Middle Aged ; S100 Proteins/metabolism ; }, abstract = {OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of cystic hypersecretory lesion (CHL) of the breast.

METHODS: Clinicopathologic and follow-up data of six cases of breast CHL in 2010-2013 were collected and reviewed.Immunohistochemical and mucinous staining was performed.

RESULTS: All six patients were female, age ranged from 37 to 71 years (average 49.3 years). Three cases were cystic hypersecretory hyperplasia (CHH), the other three cases were cystic hypersecretory carcinoma (CHC). Clinically the lesions presented as either breast mass or mammographic calcification.Grossly, the cystic hypersecretory lesions were poorly circumscribed, with multiple colloid containing cysts on the cut surface. Microscopically, the remarkable feature was numerous enlarged cysts which contained densely eosinophilic homogeneous secretion similar to the colloid seen in thyroid follicles, and calcification was seen in the cyst in one case. The secretion was D-PAS and mucicarmine positive. The lining epithelium of the cysts was uniformly flat, cuboid or columnar, and arranged in a monolayer. The cells may be arranged in turfs, solid or micropapillary patterns in CHH.In cases with dysplasia, the epithelium showed cytological and structural atypia, but the usual morphology of atypical dutal hyperplasia such as arcades, rigid bridges or cribriform pattern was less common. The three CHC included two invasive ductal carcinomas (IDC) and one ductal carcinoma in situ (DCIS).In CHL, there was immunoreactivity to S-100 protein, CK5/6 and CK14.Of the three CHCs, ER and PR were expressed in only one IDC.No HER2 expression was identified in the two invasive CHCs.One patient was lost to follow-up, and the rest were uneventful at 18 months.

CONCLUSIONS: CHL of the breast is a rare pathological entity. Multiple colloid-filled cysts is a unique histological feature. The epithelium of CHL may show usual hyperplasia, dysplasia or carcinoma.}, } @article {pmid24708809, year = {2014}, author = {Ho, CW and Mantoo, S and Lim, CH and Wong, CY}, title = {Synchronous invasive ductal carcinoma and intravascular large B-cell lymphoma of the breast: a case report and review of the literature.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {88}, pmid = {24708809}, issn = {1477-7819}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/*pathology/therapy ; Mastectomy ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology/therapy ; Prognosis ; }, abstract = {Primary breast lymphomas (PBLs) represent less than 1% of all breast malignancies. Intravascular large B-cell lymphoma (ILBCL) is a rare, aggressive form of extranodal lymphoma. Breast involvement has only been described in the literature once previously. ILBCL is characterized by the proliferation of tumour cells within the lumen of small vessels of involved organs, resulting in their eventual occlusion. Clinical features are often vague, diagnosis is difficult and delayed, and prognosis is usually poor. We report the first ever case of synchronous ILBCL and invasive ductal carcinoma (IDC) of the breast in a patient presenting with pyrexia of unknown origin and altered mental status who underwent modified radical mastectomy and subsequent chemotherapy, and review the literature regarding intravascular large B-cell lymphoma, PBLs and synchronous carcinomas and lymphomas of the breast.}, } @article {pmid24708527, year = {2014}, author = {Schoellhammer, HF and Hsu, F and Vito, C and Chu, P and Park, J and Waisman, J and Kim, J}, title = {Complete pathologic response of HER2-positive breast cancer liver metastasis with dual anti-HER2 antagonism.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {242}, pmid = {24708527}, issn = {1471-2407}, mesh = {Antibodies, Monoclonal, Humanized/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Breast Neoplasms/*drug therapy/genetics/pathology ; Clinical Trials as Topic ; Female ; Humans ; Liver Neoplasms/*drug therapy/pathology/secondary ; Middle Aged ; Molecular Targeted Therapy ; Receptor, ErbB-2/antagonists & inhibitors/*genetics ; Trastuzumab ; }, abstract = {BACKGROUND: Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease.

CASE PRESENTATION: We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM.

CONCLUSIONS: The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.}, } @article {pmid24707803, year = {2014}, author = {George-Levi, S and Vilchinsky, N and Tolmacz, R and Liberman, G}, title = {Testing the concept of relational entitlement in the dyadic context: further validation and associations with relationship satisfaction.}, journal = {Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)}, volume = {28}, number = {2}, pages = {193-203}, doi = {10.1037/a0036150}, pmid = {24707803}, issn = {1939-1293}, mesh = {Adult ; Data Interpretation, Statistical ; Family Characteristics ; Female ; Gender Identity ; Heterosexuality/psychology ; Humans ; *Interpersonal Relations ; Israel/epidemiology ; Male ; *Personal Satisfaction ; Personality ; Spouses/*psychology ; }, abstract = {The sense of relational entitlement is the perception one has of what one deserves from one's partner, and it may play a crucial role in determining the quality of a couple's relationship. However, the concept was only recently subjected to empirical examination. The main goals of the current study were to continue the work initiated by the scale developers (Tolmacz & Mikulincer, 2011) by (1) further validating the Sense of Relational Entitlement Scale (SRE) in a sample of adult couples; and (2) examining the contribution of each partner's sense of relational entitlement to his or her own and his or her partner's relationship satisfaction. A sample of 120 Israeli, heterosexual, older couples (age = 58 years) in long-term relationships completed the study measurements. Factor analyses revealed that the SRE scale consisted of two major dimensions: conflicted entitlement and assertive entitlement. Applying an Actor-Partner-Interdependence Model (APIM) analysis indicated that the more conflicted one felt with regard to what one was entitled to, the less satisfaction one felt with the relationship. Additionally, the higher one's entitlement expectations were of one's partner (a subfactor of the assertive entitlement dimension), the more one's partner was satisfied with the relationship. The sense of entitlement construct seems to be relevant to the context of dyadic relationships and, as such, is worthy of further attention and investigation.}, } @article {pmid24705763, year = {2014}, author = {Otomi, Y and Otsuka, H and Terazawa, K and Nose, H and Kubo, M and Matsuzaki, K and Ikushima, H and Bando, Y and Harada, M}, title = {Comparing the performance of visual estimation and standard uptake value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography for detecting malignancy in pancreatic tumors other than invasive ductal carcinoma.}, journal = {The journal of medical investigation : JMI}, volume = {61}, number = {1-2}, pages = {171-179}, doi = {10.2152/jmi.61.171}, pmid = {24705763}, issn = {1349-6867}, mesh = {Adenoma/*diagnosis/diagnostic imaging ; Adult ; Aged ; Cystadenoma, Serous/*diagnosis/diagnostic imaging ; Diagnosis, Differential ; Diagnostic Imaging/methods ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors/*diagnosis/diagnostic imaging ; Pancreas/diagnostic imaging/metabolism ; Pancreatic Neoplasms/*diagnosis/diagnostic imaging ; *Positron-Emission Tomography ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; *Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: The utility of FDG PET/CT for the detection and evaluation of invasive ductal carcinoma has been widely reported, but a few studies have assessed the utility of FDG PET/CT to detect malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma.

PURPOSE: To compare the diagnostic performance of visual estimation with the semi-quantitative scores of FDG PET/CT for detecting malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma.

MATERIAL AND METHODS: Images of pathologically proven pancreatic lesions from 32 patients were retrospectively evaluated: 14 benign lesions, 7 borderline (low malignant) lesions, and 11 malignant lesions. The average scores from visual estimation by the two observers were compared to two semi-quantitative analyses of FDG uptake in the lesions, namely the maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean).

RESULTS: Visual analysis value, SUVmax and SUVmean were 0.33 ± 0.21, 1.8 ± 0.7 and 1.5 ± 0.7 for the benign lesions, 0.70 ± 0.28, 5.0 ± 2.6 and 3.1±1.7 for the borderline lesions, and 0.73 ± 0.18, 4.7 ± 2.5 and 3.2 ± 1.6 for the malignant lesions, respectively. Receiver operating characteristic analysis revealed the areas under the curves for detecting non-benign (malignant or borderline) lesions through visual analysis, SUVmax, and SUVmean were 0.914, 0.954, and 0.875, respectively.

CONCLUSION: For a variety of pancreatic lesions other than invasive ductal carcinoma, visual analysis and semi-quantitative analyses all showed strong diagnostic performance. However, semi-quantitative analysis with SUVmax proved to be the most effective method for detecting non-benign pancreatic lesions.}, } @article {pmid24703897, year = {2014}, author = {Trudel, D and Downes, MR and Sykes, J and Kron, KJ and Trachtenberg, J and van der Kwast, TH}, title = {Prognostic impact of intraductal carcinoma and large cribriform carcinoma architecture after prostatectomy in a contemporary cohort.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {50}, number = {9}, pages = {1610-1616}, doi = {10.1016/j.ejca.2014.03.009}, pmid = {24703897}, issn = {1879-0852}, mesh = {Adenocarcinoma/mortality/*pathology/surgery ; Aged ; Carcinoma, Ductal/mortality/*pathology/surgery ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/mortality/pathology ; Prognosis ; Prostatectomy/mortality ; Prostatic Neoplasms/mortality/*pathology/surgery ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) of prostate is a distinct entity associated with higher Gleason score and poor prognosis. The prognostic significance of large cribriform Gleason pattern 4 (LC) in conjunction with IDC has not been previously investigated. The aim of our study was to determine the impact of IDC and LC on biochemical recurrence-free rate (bRFR) in a contemporary prostatectomy cohort.

METHODS: Prostate cancers of 246 prostatectomies, median follow-up 130.6 months, were graded with the International Society of Urological Pathology (ISUP) 2005 modified Gleason score (GS) and assessed for the presence of LC and/or IDC. In 57 cases with LC and/or IDC, immunostaining was performed to distinguish LC and IDC. The Kaplan-Meier (KM) method was used to estimate 5-year bRFR probabilities. Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Multivariable analysis showed that the presence of any amount of LC or IDC had a highly significant prognostic effect on bRFR (HR 2.98, 95% CI: 1.68-5.28, p=0.0002) after adjusting for GS, surgical margin status and pathological stage. Although IDC alone tended to be associated with a worse prognosis, LC and IDC did not appear to be associated with a difference in bRFR when analysed separately.

CONCLUSION: We demonstrate that the presence of any amount of LC/IDC is a significant prognostic factor after adjusting for Gleason score and T stage in determining patient outcome and we advocate including the presence of either in routine pathology reporting.}, } @article {pmid24703020, year = {2014}, author = {Kallel, R and Bahri, I and Abid, N and Feki, J and Mellouli, M and Ayadi, L and Boudawara, T}, title = {[Mixed breast carcinoma with melanocytic differentiation in a man].}, journal = {Annales de pathologie}, volume = {34}, number = {2}, pages = {115-118}, doi = {10.1016/j.annpat.2014.02.012}, pmid = {24703020}, issn = {0242-6498}, mesh = {Breast Neoplasms, Male/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/*pathology ; Humans ; Male ; Melanocytes/pathology ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; Rare Diseases/*pathology ; }, abstract = {INTRODUCTION: Male breast cancer is rare; the lobular type is exceptional. Only one case of mixed ductal and lobular type is reported in the literature. This is the first report on a mixed ductal and lobular carcinoma with melanocytic differentiation in a man. The aim of our study is to describe the clinicopathological characteristics of this rare type of breast tumor and to discuss its histogenesis.

CASE REPORT: A 63-year-old man presented with cutaneous ulceration of the left breast. Ultrasound of the breast revealed a solid hypoechoic lesion, 13 mm in diameter. Microscopic evaluation of the biopsy showed an invasive ductal carcinoma. The patient received three cycles of chemotherapy and lost of view. Then consulted for increasing of the tumor size reaching 3 cm. Histological examination of the mastectomy specimen showed a mixed ductal and lobular carcinoma with melanocytic differentiation, confirmed by the immunohistochemical study. The patient received adjuvant chemotherapy and the evolution was favorable with an average follow-up of 9 months.

CONCLUSION: Breast carcinoma with melanocytic differentiation is extremely rare; only seven cases are reported in the literature and all occurs in females. Its histogenesis is unclear; tumors exhibiting this combination of cell types may occur as collision or composite tumors.}, } @article {pmid24696740, year = {2014}, author = {Zhang, X and Liang, Y and Wang, HY}, title = {Invasive ductal carcinoma of the breast associated with extensive melanin melanosis: a case report and review of the literature.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {3}, pages = {1218-1223}, pmid = {24696740}, issn = {1936-2625}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Melanins/metabolism ; Melanosis/*pathology ; }, abstract = {Extensive melanosis of breast tissue due to melanin in the absence of involvement by melanoma either primary or secondary has been rarely encountered. Herein we report a first and unique case of extensive macroscopic and microscopic melanosis of mammary parenchyma between carcinoma cells due to melanin in a patient with a poorly differentiated invasive ductal carcinoma of the breast with no evidence of melanocytic differentiation or melanoma. In contrast to previously reported cases in the literature, there is no breach of dermal-epidermal junction and there is no dermal infiltrate in the skin overlying the carcinoma, or Pagetoid disease in the nipple.}, } @article {pmid24696720, year = {2014}, author = {Kim, SK and Jung, WH and Koo, JS}, title = {p40 (ΔNp63) expression in breast disease and its correlation with p63 immunohistochemistry.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {3}, pages = {1032-1041}, pmid = {24696720}, issn = {1936-2625}, mesh = {*Antibodies ; Biomarkers, Tumor/*analysis ; Breast Diseases/*diagnosis ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Immunohistochemistry ; Protein Isoforms/analysis/biosynthesis ; Tissue Array Analysis ; Transcription Factors/analysis/*biosynthesis ; Tumor Suppressor Proteins/analysis/*biosynthesis ; }, abstract = {p63 protein is widely used to identify myoepithelial cells in breast disease. There have been no comparative studies of the p63 antibodies which detect different isoforms. In this study, we examine the expression profiles of p63 protein in benign proliferative diseases and malignant tumors of the breast using pan-p63 and p40 antibodies, and analyze their diagnostic utility and clinical implications. We selected 32 adenoses, 34 intraductal papillomas, 31 ductal carcinoma in situ (DCIS), 257 invasive ductal carcinoma (IDC), and 36 metaplastic carcinomas, and created tissue microarray blocks from them. Immunohistochemical assays for p63 protein were performed on these samples. We investigated the expression patterns of the pan-p63 (TP63, 4A4, Dako, 1:700), p40 antibody [5-17, CalBiochem/EMD Biosciences, 1:2000, p40 (CB)], and p40 antibody [polyclonal, Diagnostic BioSystems, 1:100, p40 (DB)] in various forms of breast disease. We determined that p63 and p40 (DB) expression in myoepithelial cells was broadly similar and showed cognate clinicopathologic features, unlike p40 (CB). p40 (CB) was more sensitive (99.0%) but less specific (85.8%), and p63 was less sensitive (93.8%) in adenosis, IP, and DCIS. In IDCs, p63 and p40 (DB) had similar expression in cancer cells; p40 (CB) expression, however, was statistically different. In metaplastic carcinomas, both p63 and p40 (DB) had distinct expression profiles, according to their histologic subtypes. We conclude that p40 antibodies as well as pan-p63 antibody are specific and sensitive myoepithelial cell markers. Interpretation of p40 positivity in cancer cells, however, should be considered carefully, due to their relatively lower specificity.}, } @article {pmid24692105, year = {2014}, author = {Yaakobi, E and Mikulincer, M and Shaver, PR}, title = {Parenthood as a Terror Management Mechanism: The Moderating Role of Attachment Orientations.}, journal = {Personality & social psychology bulletin}, volume = {40}, number = {6}, pages = {762-774}, doi = {10.1177/0146167214525473}, pmid = {24692105}, issn = {1552-7433}, abstract = {Six studies examined the hypothesis that parenthood serves a terror management function, with effects that are moderated by attachment orientations. In Studies 1 and 2, mortality salience, as compared with control conditions, increased the self-reported vividness and implicit accessibility of parenthood-related cognitions. In Studies 3 and 4, activating parenthood-related thoughts reduced death-thought accessibility and romantic intimacy following mortality salience. In Study 5, heightening the salience of parenthood-related obstacles increased death-thought accessibility. Across the five studies, the effects were significant mainly among participants who scored relatively low on avoidant attachment. In Study 6, avoidant people also reacted to mortality salience with more positive parenthood-related cognitions following an experimental manipulation that made parenthood compatible with their core strivings. Overall, the findings suggest that parenthood can have an anxiety-buffering effect that is moderated by attachment-related avoidance.}, } @article {pmid24691501, year = {2014}, author = {Wahler, J and So, JY and Kim, YC and Liu, F and Maehr, H and Uskokovic, M and Suh, N}, title = {Inhibition of the transition of ductal carcinoma in situ to invasive ductal carcinoma by a Gemini vitamin D analog.}, journal = {Cancer prevention research (Philadelphia, Pa.)}, volume = {7}, number = {6}, pages = {617-626}, pmid = {24691501}, issn = {1940-6215}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 CA127645/CA/NCI NIH HHS/United States ; ES005022/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*drug therapy/*pathology ; Calcitriol/*analogs & derivatives/chemistry/therapeutic use ; Carcinoma, Ductal, Breast/pathology/*prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/*pathology ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Epithelial-Mesenchymal Transition/*drug effects ; Female ; Humans ; Mice ; Mice, Nude ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Ductal carcinoma in situ (DCIS) is a nonmalignant lesion of the breast with the potential to progress to invasive ductal carcinoma (IDC). The disappearance and breakdown of the myoepithelial cell layer and basement membrane in DCIS have been identified as major events in the development of breast cancer. The MCF10DCIS.com cell line is a well-established model, which recapitulates the progression of breast cancer from DCIS to IDC. We have previously reported that a novel Gemini vitamin D analog, 1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (BXL0124) is a potent inhibitor of the growth of MCF10DCIS.com xenografted tumors without hypercalcemic toxicity. In this study, we utilized the MCF10DCIS.com in vivo model to assess the effects of BXL0124 on breast cancer progression from weeks 1 to 4. Upon DCIS progression to IDC from weeks 3 to 4, tumors lost the myoepithelial cell layer and basement membrane as shown by immunofluorescence staining with smooth muscle actin and laminin 5, respectively. Administration of BXL0124 maintained the critical myoepithelial cell layer as well as basement membrane, and animals treated with BXL0124 showed a 43% reduction in tumor volume by week 4. BXL0124 treatment decreased cell proliferation and maintained vitamin D receptor levels in tumors. In addition, the BXL0124 treatment reduced the mRNA levels of matrix metalloproteinases starting at week 3, contributing to the inhibition of invasive transition. Our results suggest that the maintenance of DCIS plays a significant role in the cancer preventive action of the Gemini vitamin D BXL0124 during the progression of breast lesions.}, } @article {pmid24689830, year = {2014}, author = {Marco, V and Muntal, T and García-Hernandez, F and Cortes, J and Gonzalez, B and Rubio, IT}, title = {Changes in breast cancer reports after pathology second opinion.}, journal = {The breast journal}, volume = {20}, number = {3}, pages = {295-301}, doi = {10.1111/tbj.12252}, pmid = {24689830}, issn = {1524-4741}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology ; Diagnostic Errors ; Female ; Humans ; Lung Neoplasms/pathology ; Receptor, ErbB-2/metabolism ; *Referral and Consultation/statistics & numerical data ; }, abstract = {Breast cancer pathology reports contain valuable information about the histologic diagnosis, prognostic factors and predictive indicators of therapeutic response. A second opinion may be requested by medical oncologists and surgeons, when a patient is referred from another institution for treatment. We report the experience with pathology second opinion in selected patients referred to the Breast Oncology Unit. 205 cases referred to the Breast Oncology Unit were selected for second opinion after clinical evaluation, between 2002 and 2012. The cases reviewed included 102 core needle biopsies, 88 surgical specimens from the breast and 18 lymphadenopathies, 14 from the axillary region. Pathology second opinion was based on a review of hematoxylin-eosin preparations, recuts of submitted paraffin blocks and written external pathology reports. Immunohistochemical studies for hormone receptors, HER2, myoepithelial cells, and other markers were performed in selected cases. A case was reclassified as showing major change when second opinion showed a potential for significant change in prognosis or treatment. Otherwise, it was considered to represent minor change or to be concordant. In 52 cases (25.4%), the pathology review showed changes. Thirty-three (16%) patients were reclassified for major changes and 19 (9.2%) as minor changes. In six patients, more than one major change was identified. The major discrepancies identified were related to the histologic classification (12 cases), the presence or absence of invasion in ductal carcinoma (15 cases), the results of hormone receptors (5 cases), and HER2 (7 cases). Major changes in histologic classification included two cases diagnosed as invasive ductal carcinoma and reclassified as benign, four cases with diagnosis of breast cancer reclassified as metastatic lung cancer, one case diagnosed as small cell carcinoma of lung metastatic in the breast, reclassified as primary carcinoma of the breast, and three cases with diagnosis of breast cancer in the axilla reclassified as primary cutaneous adnexal carcinomas (2) and metastatic melanoma (1), respectively. In two cases, the histologic type of the primary breast tumor was changed. Second opinion in breast pathology may uncover significant discrepancies that impact on patient management and prognosis. Major discrepancies are most frequently related to the assessment of the presence or absence of invasion in ductal carcinoma, the results of predictive makers of therapeutic response, and the differential diagnosis of breast cancer and nonmammary tumors in the breast, the axilla, and at distant sites.}, } @article {pmid24687377, year = {2014}, author = {Yang, F and Zhou, X and Miao, X and Zhang, T and Hang, X and Tie, R and Liu, N and Tian, F and Wang, F and Yuan, J}, title = {MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis.}, journal = {Breast cancer research and treatment}, volume = {145}, number = {1}, pages = {23-32}, pmid = {24687377}, issn = {1573-7217}, mesh = {Adult ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/analysis ; Blotting, Western ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Epithelial-Mesenchymal Transition/physiology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Prognosis ; Risk Factors ; Tissue Array Analysis ; }, abstract = {MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.}, } @article {pmid24679013, year = {2014}, author = {Serra-Majem, L and Riobó Serván, P and Belmonte Cortés, S and Anadón Navarro, A and Aranceta Bartrina, J and Franco Vargas, E and García-Closas, R and Gómez-Candela, C and Herrero Sancho, E and La Vecchia, C and López Díaz-Ufano, ML and Varela-Moreiras, G and Vázquez Castro, J and Ribas-Barba, L and Alcaraz-Cebrián, F and García-Luna, PP and González-Gomis, M and González-Gross, M and Granado de la Orden, S and López-Sobaler, AM and Moreno Villares, JM and Ortega Anta, RM and Pérez-Rodrigo, C and Polanco Allué, I and Urrialde de Andrés, R}, title = {Chinchón declaration; decalogue on low- and no-calorie sweeteners (LNCS).}, journal = {Nutricion hospitalaria}, volume = {29}, number = {4}, pages = {719-734}, doi = {10.3305/nh.2014.29.4.7393}, pmid = {24679013}, issn = {1699-5198}, mesh = {Body Weight ; Dental Health Surveys ; History, 20th Century ; Humans ; Legislation, Food ; *Sweetening Agents/adverse effects/history ; Taste/physiology ; }, abstract = {Multidisciplinary experts in the areas of nutrition and health met in Chinchón, Madrid, on November 25-26, 2013 under the auspices of the Fundación para la Investigación Nutricional (Nutrition Research Foundation) and with the collaboration of the Madrid Regional Government's Health Ministry, the International Sweeteners Association and the Carlos III Health Institute CIBER of Physiopathology of Obesity and Nutrition. They analyzed the current status of scientific knowledge on low- and no-calorie sweeteners (LNCS) and developed a consensus Decalogue on their use; this constitutes the Chinchón Declaration. Sweeteners, including sugar, represent a subject of undeniable interest and are currently a popular topic, although areas relating to their safety and benefits remain unknown to segments of academia and the general public. The nature of LNCS makes them vulnerable to biased and even contradictory information. They are food additives that are broadly used as sugar substitutes to sweeten foods, medicines and food supplements when non-nutritional or non-caloric alternatives are needed. The Chinchón Decalogue is the outcome of a meeting for reflection and consensus by a group of experts with backgrounds in different scientific disciplines (toxicology, clinical nutrition, community nutrition, physiology, food science, public health, pediatrics, endocrinology and nutrition, nursing, pharmaceutical care and food legislation). The Decalogue includes different aspects of LNCS related to regulation, use, benefits and safety. In general, benefits of LNCS have been traditionally neglected in comparison with the tendency for emphasising unexisting or unproven possible risks. The need to strengthen research on LNCS in Spain was emphasized, as well as the need to educate both professionals and the public.}, } @article {pmid24676587, year = {2014}, author = {Li, J and Liu, R and Yang, Y and Huang, Y and Li, X and Liu, R and Shen, X}, title = {Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells.}, journal = {Oncology reports}, volume = {31}, number = {5}, pages = {2181-2186}, doi = {10.3892/or.2014.3115}, pmid = {24676587}, issn = {1791-2431}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Diterpenes/*pharmacology ; Drugs, Chinese Herbal/pharmacology ; Epoxy Compounds/pharmacology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells/*drug effects ; Phenanthrenes/*pharmacology ; Spheroids, Cellular/transplantation ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {We investigated the potential efficacy of the Chinese herbal extract triptolide for the treatment of human breast cancer by measuring the triptolide-induced cytotoxicity in cultures of human primary breast cancer cells (BCCs) and breast cancer stem cells (BCSCs) in vitro and in vivo. Human BCCs and BCSCs from invasive ductal carcinoma samples were cultured and treated with 0.1, 0.5 or 1.0 µM triptolide. Cell death and apoptosis were measured after 24, 48 and 72 h of treatment. Mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. Triptolide was cytotoxic against both human primary BCCs and BCSCs in vitro (P<0.05), but the cytotoxicity was stronger against the BCCs. In response to 1 µM triptolide for 72 h, the apoptotic rates were approximately 60% for BCCs and 30% for BCSCs. The BCSCs exhibited a high formation rate of tumors when implanted subcutaneously in nude BALB/c mice. Triptolide treatment in vivo significantly inhibited tumor growth compared with mock treatment. In conclusion, the cytotoxicity of triptolide against BCCs and BCSCs in vitro and in vivo suggests that this natural diterpenoid triepoxide compound may have clinical applications for the suppression of breast tumor growth.}, } @article {pmid24672738, year = {2014}, author = {Ping, Z and Siegal, GP and Almeida, JS and Schnitt, SJ and Shen, D}, title = {Mining genome sequencing data to identify the genomic features linked to breast cancer histopathology.}, journal = {Journal of pathology informatics}, volume = {5}, number = {1}, pages = {3}, pmid = {24672738}, issn = {2229-5089}, abstract = {BACKGROUND: Genetics and genomics have radically altered our understanding of breast cancer progression. However, the genomic basis of various histopathologic features of breast cancer is not yet well-defined.

MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) is an international database containing a large collection of human cancer genome sequencing data. cBioPortal is a web tool developed for mining these sequencing data. We performed mining of TCGA sequencing data in an attempt to characterize the genomic features correlated with breast cancer histopathology. We first assessed the quality of the TCGA data using a group of genes with known alterations in various cancers. Both genome-wide gene mutation and copy number changes as well as a group of genes with a high frequency of genetic changes were then correlated with various histopathologic features of invasive breast cancer.

RESULTS: Validation of TCGA data using a group of genes with known alterations in breast cancer suggests that the TCGA has accurately documented the genomic abnormalities of multiple malignancies. Further analysis of TCGA breast cancer sequencing data shows that accumulation of specific genomic defects is associated with higher tumor grade, larger tumor size and receptor negativity. Distinct groups of genomic changes were found to be associated with the different grades of invasive ductal carcinoma. The mutator role of the TP53 gene was validated by genomic sequencing data of invasive breast cancer and TP53 mutation was found to play a critical role in defining high tumor grade.

CONCLUSIONS: Data mining of the TCGA genome sequencing data is an innovative and reliable method to help characterize the genomic abnormalities associated with histopathologic features of invasive breast cancer.}, } @article {pmid24665089, year = {2014}, author = {Baba, S and Isoda, T and Maruoka, Y and Kitamura, Y and Sasaki, M and Yoshida, T and Honda, H}, title = {Diagnostic and prognostic value of pretreatment SUV in 18F-FDG/PET in breast cancer: comparison with apparent diffusion coefficient from diffusion-weighted MR imaging.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {55}, number = {5}, pages = {736-742}, doi = {10.2967/jnumed.113.129395}, pmid = {24665089}, issn = {1535-5667}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; *Diffusion Magnetic Resonance Imaging ; ErbB Receptors/metabolism ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Middle Aged ; *Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {UNLABELLED: In oncology, the apparent diffusion coefficient (ADC) measured by diffusion-weighted MR imaging (DWI) and the standardized uptake value (SUV) from (18)F-FDG PET have similar clinical applications. The purpose of this study was to assess the correlation between the ADC and SUV and compare their potential in the diagnosis and prediction of prognosis in breast tumors.

METHODS: Seventy-nine female patients (age range, 19-69 y; average, 49.1 y) with 83 pathologically proven breast tumors were recruited. The diagnoses consisted of 70 malignant breast tumors (65 cases of invasive ductal carcinoma, 1 of medullary carcinoma, 1 of mucinous carcinoma, 1 of squamous cell carcinoma, and 2 of micropapillary carcinoma) and 13 benign breast tumors (4 cases of fibroadenoma, 4 of mastopathy, 3 of adenosis with atypia, and 2 of benign phyllodes tumor). All patients underwent mammary gland MR imaging with DWI and (18)F-FDG PET within a 2-wk interval. The patients' ADCs and SUVs were measured within the tumor by DWI and (18)F-FDG PET, respectively. For the malignant tumors, we evaluated the relationships among ADC, SUV, histopathologic appearance, and long-term prognosis.

RESULTS: A significant difference (P < 0.05) was observed in both parameters (ADC and SUV) between the benign and malignant breast tumors, and the difference was more significant when we introduced a new parameter, SUV/ADC. There was a weak inverse correlation between ADC and SUV (r = -0.36; P = 0.06) among the total tumors; however, this correlation was not significant within the group of malignant tumors. High SUV was found to correlate with larger tumor size, higher nuclear grade, and the triple-negative hormonal receptor profile. High ADC was revealed to be correlated with negative progesterone receptor and positive human epidermal growth factor receptor 2 profile. Higher SUVs also showed a correlation with poor prognosis. No correlation was seen between ADC and prognosis.

CONCLUSION: Both SUV and ADC are helpful parameters in differentiating benign from malignant breast tumors. The use of SUV and ADC in combination may help in the diagnosis because of their inverse relationship. High preoperative SUV was associated with poor prognosis, but the contribution of ADC to prognosis prediction was small.}, } @article {pmid24658871, year = {2014}, author = {Nogueira, L and Brandão, S and Matos, E and Nunes, RG and Loureiro, J and Ramos, I and Ferreira, HA}, title = {Application of the diffusion kurtosis model for the study of breast lesions.}, journal = {European radiology}, volume = {24}, number = {6}, pages = {1197-1203}, pmid = {24658871}, issn = {1432-1084}, mesh = {Adult ; *Algorithms ; Breast/*pathology ; Breast Neoplasms/*diagnosis ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Follow-Up Studies ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; }, abstract = {OBJECTIVES: To evaluate diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in the differentiation and characterisation of breast lesions.

METHODS: Thirty-six women underwent breast magnetic resonance imaging (MRI) including a DWI sequence with multiple b-values (50-3,000 s/mm(2)). Mean values for apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were calculated by lesion type and histological subtype. Differences and correlation between parameters were determined.

RESULTS: Forty-four lesions were found. There were significant differences between benign and malignant lesions for all parameters (ADC, p = 0.017; MD, p = 0.028; MK, p = 0.017). ADC and MD were higher for benign (1.96 ± 0.41 × 10(-3) and 2.17 ± 0.42 × 10(-3) mm(2)/s, respectively) than for malignant lesions (1.33 ± 0.18 × 10(-3) and 1.52 ± 0.50 × 10(-3) mm(2)/s). MK was higher for malignant (0.61 ± 0.27) than benign lesions (0.37 ± 0.18). We found differences between invasive ductal carcinoma (IDC) and fibroadenoma (FA) for all parameters (ADC, MD and MK): p = 0.016, 0.022 and 0.016, respectively. FA and fibrocystic change (FC) showed differences only in MK (p = 0.016).

CONCLUSIONS: Diffusion in breast lesions follows a non-Gaussian distribution. MK enables differentiation and characterisation of breast lesions, providing new insights into microstructural complexity. To confirm these results, further investigation in a broader sample should be performed.}, } @article {pmid24655736, year = {2014}, author = {Moccia, M and Picillo, M and Erro, R and Vitale, C and Amboni, M and Palladino, R and Cioffi, DL and Barone, P and Pellecchia, MT}, title = {How does smoking affect olfaction in Parkinson's disease?.}, journal = {Journal of the neurological sciences}, volume = {340}, number = {1-2}, pages = {215-217}, doi = {10.1016/j.jns.2014.02.018}, pmid = {24655736}, issn = {1878-5883}, mesh = {Aged ; Analysis of Variance ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Olfaction Disorders/*etiology ; Parkinson Disease/*complications ; Severity of Illness Index ; *Smoking ; }, abstract = {Smoke-induced upper airway damage and Parkinson's disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate the relationship between smoking and olfaction in PD patients and matched controls. Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of the University of Pennsylvania 40-item Smell Identification Test (UPSIT-40). ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p<0.001), non-smoker PD patients (p<0.001) and smoker PD patients (p<0.001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients. Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact.}, } @article {pmid24654594, year = {2014}, author = {Son, CH and Bae, JH and Shin, DY and Lee, HR and Yang, K and Park, YS}, title = {Antitumor effect of dendritic cell loaded ex vivo and in vivo with tumor-associated antigens in lung cancer model.}, journal = {Immunological investigations}, volume = {43}, number = {5}, pages = {447-462}, doi = {10.3109/08820139.2014.884576}, pmid = {24654594}, issn = {1532-4311}, mesh = {Animals ; Antigens, Neoplasm/*immunology ; Cancer Vaccines/administration & dosage/*immunology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Injections, Intralesional ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis ; Lung Neoplasms/*immunology/mortality/therapy ; Male ; Mice ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocyte Subsets/immunology/metabolism ; }, abstract = {Various ex vivo or in vivo loading protocols have been developed or evaluated for the delivery of tumor antigens to dendritic cells (DCs). We compared the antitumor effect of mature DCs electroporation-pulsed (EP/mDC) ex vivo with tumor cell lysate and immature DCs (iDCs) injected into the tumor apoptosed by ionizing radiation (IR/iDC) in lung cancer model. DCs were generated from bone marrow of C57BL/6 mice. Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh. iDCs were intratumorally injected into the irradiated tumor and EP/mDC was injected subcutaneously in the right flank. DC injection induced strong tumor-specific immunity against Lewis lung carcinoma, as compared with the tumor-bearing control and IR only treated mice. The growth of a distant tumor on the right and left flank was inhibited by IR/iDC and EP/mDC. Particularly, IR/iDC resulted in a more significant inhibition of tumor growth and prolonged survival time. It was related to increase of tumor-specific interferon-gamma, cytotoxicity, and decrease of regulatory T-cells. The results indicate that DCs electroporation-pulsed with tumor cell lysate induce a potent antitumor effect, but that iDCs intratumoral injected into the irradiated tumor induce a more potent antitumor effect.}, } @article {pmid24652427, year = {2014}, author = {Teo, SY and Chuwa, E and Latha, S and Lew, YL and Tan, YY}, title = {Young breast cancer in a specialised breast unit in Singapore: clinical, radiological and pathological factors.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {43}, number = {2}, pages = {79-85}, pmid = {24652427}, issn = {0304-4602}, mesh = {Adolescent ; Adult ; Age Factors ; *Breast Neoplasms/diagnosis/epidemiology/surgery ; Female ; Hospital Units ; Humans ; Retrospective Studies ; Singapore ; Young Adult ; }, abstract = {INTRODUCTION: Whilst only 5.5% to 7% of breast cancer occurs in women less than 40 years of age in the West, the incidence has been reported in up to 18% in Asian population. This study seeks to evaluate our unit's experience in breast cancer in young women.

MATERIALS AND METHODS: A retrospective review of our database identified women with newly diagnosed breast cancer from January 2006 to February 2011. Patient demographics, clinical presentation, imaging and pathological findings and treatment received were determined.

RESULTS: Out of a total of 1160 women with breast cancer, 135 (11.6%) were under 40 years of age and made up our study population. The most common presentation was a self-detected breast lump. Most patients did not have a positive family history. Mammography demonstrated abnormal findings in 78% of patients. Ultrasound was very sensitive in the evaluation of a breast lump and demonstrated abnormal findings in 95%. Out of 129 women, 40 (31%) underwent breast-conserving surgery of which 5 (12.5%) proceeded to mastectomy due to involved margins. Also, 89 out of 129 women (69%) underwent mastectomy of which 19 (21.3%) had immediate reconstruction. Of a total of 121 primary resections, 94% were invasive ductal carcinoma while 15.5% were pure ductal in-situ carcinomas. The majority (61.2%) showed high grade disease.

CONCLUSION: Most young breast cancer patients present with a self-detected breast lump and do not have a positive family history. A strong clinical index of suspicion and appropriate breast imaging workup are useful for the early and accurate diagnosis of breast cancer in young women.}, } @article {pmid24652232, year = {2014}, author = {Yoon, HJ and Kang, KW and Chun, IK and Cho, N and Im, SA and Jeong, S and Lee, S and Jung, KC and Lee, YS and Jeong, JM and Lee, DS and Chung, JK and Moon, WK}, title = {Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from [68]Ga-RGD PET/CT and [18]F-FDG PET/CT.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {41}, number = {8}, pages = {1534-1543}, pmid = {24652232}, issn = {1619-7089}, mesh = {Adult ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*diagnosis/diagnostic imaging/genetics ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/genetics ; Coordination Complexes ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Multimodal Imaging ; Oligopeptides ; *Positron-Emission Tomography ; Radiopharmaceuticals ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/*genetics/metabolism ; Tomography, X-Ray Computed ; }, abstract = {PURPOSE: Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.

METHODS: In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). (68)Ga-Labeled arginine-glycine-aspartic acid (RGD) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUVmax and SUVavg) from RGD PET/CT and SUVmax and SUVavg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered.

RESULTS: Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUVmax; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUVavg) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUVavg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUVmax; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUVavg) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUVmax and r = 0.46, p < 0.01 for SUVavg). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR-,Her2- subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR-,Her2- subgroup showed a significant positive correlation between FDG and RGD PET parameters (r = 0.59, p = 0.03 for SUVmax).

CONCLUSION: (68)Ga-RGD and (18)F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.}, } @article {pmid24648320, year = {2015}, author = {Nakiwogga-Muwanga, A and Musaazi, J and Katabira, E and Worodria, W and Talisuna, SA and Colebunders, R}, title = {Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda.}, journal = {International journal of STD & AIDS}, volume = {26}, number = {1}, pages = {42-47}, doi = {10.1177/0956462414529098}, pmid = {24648320}, issn = {1758-1052}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Appointments and Schedules ; CD4 Lymphocyte Count ; Continuity of Patient Care/*organization & administration ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/psychology ; Humans ; *Lost to Follow-Up ; Male ; Middle Aged ; Patient Compliance/psychology/*statistics & numerical data ; Patient Dropouts/psychology/*statistics & numerical data ; Socioeconomic Factors ; Time Factors ; Treatment Outcome ; Treatment Refusal ; }, abstract = {We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8-90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients' changing needs and their preference for self-management.}, } @article {pmid24647056, year = {2014}, author = {Nakagawa, M and Miyati, T and Hayashi, T and Kanao, S and Taniguchi, M and Higashimura, K and Toi, M and Togashi, K}, title = {[Triexponential diffusion analysis in invasive ductal carcinoma and fibroadenoma].}, journal = {Nihon Hoshasen Gijutsu Gakkai zasshi}, volume = {70}, number = {3}, pages = {199-205}, doi = {10.6009/jjrt.2014_jsrt_70.3.199}, pmid = {24647056}, issn = {0369-4305}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal/*diagnosis/pathology ; Diffusion Magnetic Resonance Imaging/instrumentation/*methods ; Female ; Fibroadenoma/*diagnosis/pathology ; Humans ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {To simultaneously obtain information on diffusion and perfusion in breast lesions by diffusion-weighted magnetic resonance imaging (DWI), we analyzed three diffusion components using a triexponential function. Eighteen subjects [10 with invasive ductal carcinoma (IDC), 8 with fibroadenoma] were evaluated using DWI with multiple b-values. We derived perfusion-related diffusion, fast free diffusion, and slow restricted diffusion coefficients (Dp, Df, Ds) calculated from the triexponential function using the DWI data. Moreover, the triexponential analysis was compared with biexponential and monoexponential analyses. Each diffusion coefficient with a triexponential function was correlated to a relative enhancement ratio (RER) using dynamic contrast-enhanced MRI. In triexponential analysis, Dp and Ds in IDC were significantly higher than those for fibroadenoma. There was no correlation between each diffusion coefficient from the triexponential analysis in any of the groups (Dp, Df, and Ds), but biexponential analysis revealed a positive correlation between each diffusion coefficient in breast lesions. Strong correlations were found between Dp and RERs. Triexponential analysis thus makes it possible to obtain, in noninvasive fashion, more detailed diffusion and perfusion information in breast lesions.}, } @article {pmid24641378, year = {2014}, author = {Wang, LW and Yang, GF and Chen, JM and Yang, F and Yuan, JP and Sun, SR and Chen, C and Hu, MB and Li, Y}, title = {A clinical database of breast cancer patients reveals distinctive clinico-pathological characteristics: a study from central China.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {15}, number = {4}, pages = {1621-1626}, doi = {10.7314/apjcp.2014.15.4.1621}, pmid = {24641378}, issn = {2476-762X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asian People ; Breast Neoplasms/*epidemiology/*pathology/surgery ; China/epidemiology ; Databases, Factual ; Female ; Humans ; Mastectomy, Radical ; Mastectomy, Segmental ; Mastectomy, Simple ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/metabolism ; White People ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common malignant tumor in females worldwide. Many differences exist in clinico-pathological characteristics of breast cancer patients between China and Western countries. This study aimed to analyze clinico-pathological characteristics of breast cancer from central China.

METHODS: Clinico- pathological information on breast cancer from three hospitals in central China was collected and analyzed.

RESULTS: From 1994 to 2012, 2,525 patients with a median age 50 years were included in this study. The 45-49-year age group and invasive ductal carcinoma not otherwise specified accounted for the highest proportions (19.1%, 480/2,525 and 81.0%, 1,982/2,446). Stages 0-I, II and III accounted for 28.0% (682/2,441), 48.4% (1,180/2,441), and 23.7% (578/2,441), respectively. Distribution of N stage showed that N0 accounted for 53.2% (1,344/2,525), and proportion of N0 rose from 51.1% (157/307) in 30-39-year age group to 64.3% (110/171) in ≥ 70-year age group, with an average increase of 2.1% in each age group. Modified radical mastectomy, radical mastectomy, breast-conserving surgery and simple mastectomy were performed for 71.8% (1,812/2,525), 18.0% (454/2,525), 5.2% (131/2,525) and 2.6% (66/2,525), respectively. Proportions of breast-conserving surgery in age ≤ 44-year group (68/132, 51.5%) and simple mastectomy in age ≥ 60-year group (57/89, 64.0%) were higher than in the other age groups. Breast cancers positive for estrogen receptor accounted for 53.0% (1,107/ 2,112). The comparisons among this study and other reports showed higher proportion of younger patients, lower proportion of breast- conserving surgery and positive estrogen receptor patients in China than western countries.

CONCLUSIONS: Clinico-pathological characteristics in this study demonstrated clear differences between the center of China than Western countries. Additional classification systems should be developed to guide grading of early breast cancer more accurately, especially for N0 patients. Invasive ductal carcinoma is a focus for intensive research.}, } @article {pmid24640805, year = {2014}, author = {Soomro, R and Beg, MA and ur Rahman, SS}, title = {Discordance of biomarker status in recurrent breast cancer.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {64}, number = {2}, pages = {163-165}, pmid = {24640805}, issn = {0030-9982}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/surgery ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Incidence ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis/epidemiology/*metabolism ; Pakistan/epidemiology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {OBJECTIVE: To study the pattern of percentage change of biomarker status in recurrent breast cancer and to compare it with its primary biomarker.

METHODS: Patients with recurrent breast disease presenting to the Breast Unit of Liaquat National Hospital and Medical College, Karachi, between January 2004 and January 2011 were included in this study. Outcome of interest was any change in the biomarker status of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2/neu) with respect to their respective primary status. SPSS 18 was used for statistical analysis.

RESULTS: The study had a total of 58 female patients with biopsy-proven recurrent breast carcinoma with a mean age of 46 +/- 11.3 years. Time to recurrence varied between 2 to 3 years with a mean of 2.3 +/- 1.9 years. Invasive ductal carcinoma was the most prevalent recurrent tumour (50/58 patients: 86%). There was a change of 25.9% in oestrogen receptor status (p < 0.01); change of 36.2% in progesterone receptor status (p = 0.036); and 22.4% change in Her2/neu status (p = < 0.01). Of the 42 (72.27%) patients who were triple negative at presentation, 30 (71.4%) remained triple negative (p = 0.02). Six of the 16 (37.5%) patients became triple negative upon recurrence (p < 0.01).

CONCLUSIONS: The study demonstrated that there was indeed a change in biomarker status in patients presenting with recurrent breast carcinoma. There is need for clinicians to check biomarker status in recurrent breast cancer patients as it may assist a shift in the management plan.}, } @article {pmid24634677, year = {2014}, author = {Sekar, P and Bharti, JN and Nigam, JS and Sharma, A and Soni, PB}, title = {Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors.}, journal = {Journal of oncology}, volume = {2014}, number = {}, pages = {702527}, pmid = {24634677}, issn = {1687-8450}, abstract = {Background. Study of tumor molecular characteristics is necessary to understand both the risk of breast cancer recurrence and the response to therapy. Aims. To evaluate p53, HoxD10, and E-cadherin status in breast cancer and to correlate with histological grade and other prognostic factors. Material and Methods. The study was conducted in 60 cases of invasive ductal carcinoma NOS with 20 cases belonging to each grade and evaluation of p53 was done by IHC and that of HoxD10 and E Cadherin status by PCR and correlation was done with histological grade and other prognostic factors. Result. p53 expression was seen in 71.67% (43/60) of the tumors. HoxD10 gene was downregulated in 46.67% (28/60) of the tumors. p53 overexpression and lower HoxD10 mRNA levels showed statistically significant association higher histological grade of the tumor (P < 0.05). CDH1 gene mutation was seen in 60% (15/25) of the tumors. No significant association was found between p53 expression, HoxD10 gene, CDH1 gene mutation, and other prognostic factors. Conclusion. p53 over expression and lower HoxD10 mRNA levels were found to be significantly associated with higher grade tumours. This suggests that p53 and HoxD10 gene play an important tumor suppressor role and the loss of which results in breast cancer progression.}, } @article {pmid24630145, year = {2014}, author = {Icht, M and Ben-David, BM}, title = {Oral-diadochokinesis rates across languages: English and Hebrew norms.}, journal = {Journal of communication disorders}, volume = {48}, number = {}, pages = {27-37}, doi = {10.1016/j.jcomdis.2014.02.002}, pmid = {24630145}, issn = {1873-7994}, mesh = {Adolescent ; Adult ; Age Factors ; Articulation Disorders/*diagnosis ; Culture ; Female ; Humans ; *Language ; Male ; Middle Aged ; Reference Values ; Sex Factors ; Speech ; Speech Articulation Tests ; Young Adult ; }, abstract = {UNLABELLED: Oro-facial and speech motor control disorders represent a variety of speech and language pathologies. Early identification of such problems is important and carries clinical implications. A common and simple tool for gauging the presence and severity of speech motor control impairments is oral-diadochokinesis (oral-DDK). Surprisingly, norms for adult performance are missing from the literature. The goals of this study were: (1) to establish a norm for oral-DDK rate for (young to middle-age) adult English speakers, by collecting data from the literature (five studies, N=141); (2) to investigate the possible effect of language (and culture) on oral-DDK performance, by analyzing studies conducted in other languages (five studies, N=140), alongside the English norm; and (3) to find a new norm for adult Hebrew speakers, by testing 115 speakers. We first offer an English norm with a mean of 6.2syllables/s (SD=.8), and a lower boundary of 5.4syllables/s that can be used to indicate possible abnormality. Next, we found significant differences between four tested languages (English, Portuguese, Farsi and Greek) in oral-DDK rates. Results suggest the need to set language and culture sensitive norms for the application of the oral-DDK task world-wide. Finally, we found the oral-DDK performance for adult Hebrew speakers to be 6.4syllables/s (SD=.8), not significantly different than the English norms. This implies possible phonological similarities between English and Hebrew. We further note that no gender effects were found in our study. We recommend using oral-DDK as an important tool in the speech language pathologist's arsenal. Yet, application of this task should be done carefully, comparing individual performance to a set norm within the specific language.

LEARNING OUTCOMES: Readers will be able to: (1) identify the Speech-Language Pathologist assessment process using the oral-DDK task, by comparing an individual performance to the present English norm, (2) describe the impact of language on oral-DDK performance, and (3) accurately detect Hebrew speakers' patients using this tool.}, } @article {pmid24629173, year = {2014}, author = {Abe, E and Suzuki, K and Hayashi, N and Yang, Y and Li, CP and Uno, M and Akiyama, F and Yamauchi, H and Nakamura, S and Tsugawa, K and Tsunoda, H and Ohde, S and Sasano, H}, title = {Clinicopathological significance of 'atypical ductal proliferation' in core needle biopsy of the breast.}, journal = {Pathology international}, volume = {64}, number = {2}, pages = {58-66}, doi = {10.1111/pin.12135}, pmid = {24629173}, issn = {1440-1827}, mesh = {Adult ; Biopsy, Large-Core Needle ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Middle Aged ; }, abstract = {Atypical ductal proliferation or ADP has been used in histopathological diagnosis of core needle biopsy (CNB) but its details have not been well studied. Therefore, we examined the clinicopathological characteristics of the initial CNB cases diagnosed as 'ADP ' who subsequently turned out to be malignant, and compared the findings to those that did not. Among 101 cases initially diagnosed as ADP in CNB, the second biopsy revealed no carcinoma (38), ductal carcinoma in situ (DCIS) (45) and invasive carcinoma (18). Significant differences were detected between those which turned out to be carcinoma and those that did not, in the status of myoepithelial cells identified by p63 immunohistochemistry (P = 0.026) and ultrasound (US) categories (P < 0.001). We further compared the histopathological characteristics of those initially diagnosed as ADP and subsequently as DCIS or invasive ductal carcinoma (IDC) with those initially diagnosed as such. DCIS or IDC cases initially diagnosed as ADP had significantly lower Ki67 labeling index (P < 0.01, P < 0.01) and histological grade using Van nuys prognostic index (P < 0.01) or Nottingham histological grades (P < 0.01) respectively than those initially as DCIS or IDC. An assessment of myoepithelial components with US findings might contribute to determine the subsequent clinical algorithm of the patients diagnosed as ADP at initial CNB.}, } @article {pmid24628533, year = {2014}, author = {Aiad, HA and Wahed, MM and Asaad, NY and El-Tahmody, M and Elhosary, E}, title = {Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {10}, pages = {976-984}, doi = {10.1111/apm.12241}, pmid = {24628533}, issn = {1600-0463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/*pathology ; Egypt ; Female ; Humans ; Immunohistochemistry/methods ; Lymph Nodes/pathology ; Middle Aged ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Retrospective Studies ; }, abstract = {Breast carcinoma in Egyptian women is a biologically more aggressive disease than those diagnosed in Western women, although a substantial number of cases are hormone responsive. G protein-coupled receptor-30 (GPR30), a seven transmembrane domain protein, is currently recognized as an estrogen receptor. This study aimed at evaluating the expression of GPR30 in breast carcinomas of Egyptian patients and its association with clinicopathologic parameters and immunohistochemical subtypes of breast carcinoma. Immunohistochemical staining for GPR30 was applied on 51 archival formalin-fixed paraffin-embedded cases of invasive ductal carcinoma. Staining was assessed using a semiquantitative scoring system taking staining intensity and extent into consideration. GPR30 was observed in 33/51 (65%) of invasive ductal carcinoma cases. GPR30 was significantly associated with larger tumor size (p = 0.009), increased number of positive lymph nodes (p = 0.04), definite lymph-vascular invasion (LVI) (p = 0.002), peri-nodal invasion (p = 0.02), and the presence of coagulative tumor cell necrosis (p = 0.02). Moreover, a significant association between positive GPR30 expression and ER positivity (p = 0.02), as well as HER2/neu positivity (p = 0.03), were also observed. Most of the luminal A and B subtypes were GPR30 positive; however, all the triple negative cases were GPR30 negative (p = 0.010). GPR30 might contribute to the aggressive behavior of Egyptian breast carcinoma. Therefore, it could be useful in the therapeutic decision making in breast cancer patients.}, } @article {pmid24625319, year = {2014}, author = {Kang, Y and Kang, S and Li, Q and Zheng, X}, title = {Mixed epithelial and mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast: a case report.}, journal = {European journal of medical research}, volume = {19}, number = {1}, pages = {14}, pmid = {24625319}, issn = {2047-783X}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*pathology/therapy ; Carcinosarcoma/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; }, abstract = {Metaplastic breast carcinoma (MBC) is an uncommon malignancy characterized by the co-existence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. A case of a female patient aged 46 years with MBC (carcinosarcoma) is presented, including mammographic, ultrasonic, gross examination, and pathological findings. After undergoing modified radical mastectomy of the left breast and subsequent six courses of adjuvant chemotherapy and endocrine therapy, the patient is now doing well with no recurrence and metastasis. Conventional treatments for invasive ductal carcinoma (IDC) may appear to be less effective. Patients with MBC would be appropriate candidates for innovative or targeted therapy regimens.}, } @article {pmid24623017, year = {2014}, author = {Feldman, AM and Begay, RL and Knezevic, T and Myers, VD and Slavov, DB and Zhu, W and Gowan, K and Graw, SL and Jones, KL and Tilley, DG and Coleman, RC and Walinsky, P and Cheung, JY and Mestroni, L and Khalili, K and Taylor, MR}, title = {Decreased levels of BAG3 in a family with a rare variant and in idiopathic dilated cardiomyopathy.}, journal = {Journal of cellular physiology}, volume = {229}, number = {11}, pages = {1697-1702}, pmid = {24623017}, issn = {1097-4652}, support = {R01 HL147064/HL/NHLBI NIH HHS/United States ; R01 HL109209/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; 1R01HL109209-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 HL116906/HL/NHLBI NIH HHS/United States ; P01 HL091799/HL/NHLBI NIH HHS/United States ; R01 HL123093/HL/NHLBI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; Family ; Female ; Heart Failure/genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation/*genetics ; Pedigree ; Phenotype ; RNA, Messenger/genetics/metabolism ; Sequence Deletion ; }, abstract = {The most common cause of dilated cardiomyopathy and heart failure (HF) is ischemic heart disease; however, in a third of all patients the cause remains undefined and patients are diagnosed as having idiopathic dilated cardiomyopathy (IDC). Recent studies suggest that many patients with IDC have a family history of HF and rare genetic variants in over 35 genes have been shown to be causative of disease. We employed whole-exome sequencing to identify the causative variant in a large family with autosomal dominant transmission of dilated cardiomyopathy. Sequencing and subsequent informatics revealed a novel 10-nucleotide deletion in the BCL2-associated athanogene 3 (BAG3) gene (Ch10:del 121436332_12143641: del. 1266_1275 [NM 004281]) that segregated with all affected individuals. The deletion predicted a shift in the reading frame with the resultant deletion of 135 amino acids from the C-terminal end of the protein. Consistent with genetic variants in genes encoding other sarcomeric proteins there was a considerable amount of genetic heterogeneity in the affected family members. Interestingly, we also found that the levels of BAG3 protein were significantly reduced in the hearts from unrelated patients with end-stage HF undergoing cardiac transplantation when compared with non-failing controls. Diminished levels of BAG3 protein may be associated with both familial and non-familial forms of dilated cardiomyopathy.}, } @article {pmid24621503, year = {2014}, author = {Mercier, I and Gonzales, DM and Quann, K and Pestell, TG and Molchansky, A and Sotgia, F and Hulit, J and Gandara, R and Wang, C and Pestell, RG and Lisanti, MP and Jasmin, JF}, title = {CAPER, a novel regulator of human breast cancer progression.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {8}, pages = {1256-1264}, pmid = {24621503}, issn = {1551-4005}, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Cell Cycle Checkpoints ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; MCF-7 Cells ; Mice, Nude ; Neoplasm Transplantation ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Proliferating Cell Nuclear Antigen/metabolism ; Protein Biosynthesis ; Proto-Oncogene Proteins c-jun/metabolism ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {CAPER is an estrogen receptor (ER) co-activator that was recently shown to be involved in human breast cancer pathogenesis. Indeed, we reported increased expression of CAPER in human breast cancer specimens. We demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER was expressed at higher levels in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specimens, where it assumed a predominantly nuclear distribution. However, the functional role of CAPER in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPER in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPER shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPER expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPER shRNAs developed smaller tumors than mice injected with MCF-7 cells harboring control shRNAs. Mechanistically, tumors derived from mice injected with MCF-7 cells harboring CAPER shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways.}, } @article {pmid24621330, year = {2014}, author = {Lim, ST and Yu, JH and Park, HK and Moon, BI and Ko, BK and Suh, YJ}, title = {A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {56}, pmid = {24621330}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/*secondary/therapy ; Carcinoma, Lobular/epidemiology/mortality/*secondary/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Republic of Korea/epidemiology ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype.

METHODS: We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n = 14,547) and ILC (n = 528).

RESULTS: The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype.

CONCLUSIONS: Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.}, } @article {pmid24609797, year = {2015}, author = {Caliskan, M and Gullu, H and Erdogan, D and Ozulku, M and Kulaksızoglu, S and Ciftci, O and Muderrisoglu, H}, title = {Association between serum total antioxidant status and coronary microvascular function in idiopathic dilated cardiomyopathy.}, journal = {Herz}, volume = {40}, number = {3}, pages = {487-494}, pmid = {24609797}, issn = {1615-6692}, mesh = {Adolescent ; Adult ; Aged ; Antioxidants/*analysis ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/*complications/diagnosis ; Coronary Artery Disease/*blood/*complications/diagnosis ; Cytokines/*blood ; Female ; Humans ; Male ; Microvessels/diagnostic imaging ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography ; Young Adult ; }, abstract = {BACKGROUND: Coronary microvascular impairment may cause myocardial ischemia and systolic dysfunction in patients with idiopathic dilated cardiomyopathy (IDC).

PATIENTS AND METHODS: The study included 41 patients with IDC and 33 healthy control subjects. Serum total antioxidant status (TAS), serum interleukin (IL)-6 levels, and tumor necrosis factor (TNF)-α levels were assayed and coronary flow reserve (CFR) was measured in all subjects via echocardiography.

RESULTS: High-sensitivity C-reactive protein (hsCRP) levels were significantly higher in patients with IDC than in the control group (3.42 ± 2.14 vs. 1.91± 1.40, p = 0.001). Serum TAS was statistically lower in patients with IDC than in controls (1.23 ± 0.16 vs. 1.77 ± 0.12, p < 0.001). CFR was statistically and significantly lower in the IDC group (2.10 ± 0.39 vs. 3.09 ± 0.49, p < 0.001). The IDC group was subsequently subdivided into two groups according to CFR values, as CFR ≥ 2 and CFR < 2. HsCRP (4.30 ± 2.42 vs. 2.58 ± 1.42, p = 0.01), TNF-α (16.67 ± 8.08 vs. 10.97 ± 1.63, p = 0.01), and IL-6 (7.54 ± 6.16 vs. 3.14 ± 1.10, p = 0.05) values were significantly higher in the CFR < 2 group compared with the higher CFR group. TAS (1.3 ± 0.16 vs. 1.14 ± 0.10, p < 0.001) was significantly lower in the CFR < 2 group. CFR correlated significantly with hsCRP, TAS, red cell distribution width (RDW), IL-6, and TNF-α.

CONCLUSION: Plasma proinflammatory cytokine levels are increased in patients with IDC. CFR was impaired as a reflection of impaired coronary microvascular dysfunction in association with increasing plasma proinflammatory cytokine levels and hsCRP levels.}, } @article {pmid24606817, year = {2014}, author = {Jaramillo-Rodríguez, Y and Cerda-Flores, RM and Ruiz-Ramos, R and López-Márquez, FC and Calderón-Garcidueñas, AL}, title = {YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.}, journal = {Archives of medical research}, volume = {45}, number = {3}, pages = {223-228}, doi = {10.1016/j.arcmed.2014.01.010}, pmid = {24606817}, issn = {1873-5487}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Adult ; Aged ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphoproteins/*metabolism ; Transcription Factors ; YAP-Signaling Proteins ; }, abstract = {BACKGROUND AND AIMS: Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma.

METHODS: There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel).

RESULTS: There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%).

CONCLUSIONS: YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC.}, } @article {pmid24605219, year = {2014}, author = {Demirhan, O and Ordu, C and Toker, A}, title = {Prolonged pleural catheters in the management of pleural effusions due to breast cancer.}, journal = {Journal of thoracic disease}, volume = {6}, number = {2}, pages = {74-78}, pmid = {24605219}, issn = {2072-1439}, abstract = {BACKGROUND: Breast cancer is the second most common etiologic cause in malignant pleural effusions (MPE). The aim of this study was to investigate the efficacy of long term pleural catheters in inducing self sclerosis in pleural effusions of breast cancer patients.

METHODS: In this study, 26 patients with breast cancer relapleural effusions that occurred between January 2011 and July 2013, who were considered not to undergo any other treatments and managed with prolonged pleural catheters (Jackson-Pratt silicone flat drain), were retrospectively analyzed. Thirty pleural catheters were inserted in 26 patients. All patients were female, mean age was 52 (range, 37-66) years old. Drainage over 1,500 mL per day was not allowed in order to avoid a lung edema. The catheters were removed in patients who had restoration of lung expansion and drainage under 50 mL/day.

RESULTS: The histologic subtypes in pleural effusions were invasive ductal carcinoma in 18 patients, ductal carcinoma in situ in 4, invasive lobular carcinoma in 2, tubular carcinoma in 1, and medullary carcinoma in 1. Three of the 26 patients underwent bilateral catheter insertion, and one patient underwent a reinsertion of the catheter into the same hemithorax due to a recurrence. The catheters were retained for a mean period of 18 days (range, 11-38 days). In one patient with invasive ductal carcinoma and paramalignant pleural effusion (PMPE) (3.8%), a recurrent pleural effusion was seen 34 days after removal of the catheter. There were no complications. One patient died while the catheter was in place.

CONCLUSIONS: Prolonged catheters for the management of pleural effusions in selected patients have become more popular than other treatment alternatives due to a shorter length of stay and lower costs. We recommend the use of Jackson Pratt (JP) silicone flat drains which in our opinion provide effective pleurodesis in addition to easy application in recurrent effusions caused by breast cancer.}, } @article {pmid24603690, year = {2014}, author = {Yin, J and Liu, Z and Li, H and Sun, J and Chang, X and Liu, J and He, S and Li, B}, title = {Association of PKCζ expression with clinicopathological characteristics of breast cancer.}, journal = {PloS one}, volume = {9}, number = {6}, pages = {e90811}, pmid = {24603690}, issn = {1932-6203}, mesh = {Adult ; Breast Neoplasms/*enzymology/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/mortality/secondary ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Isoenzymes/*metabolism ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Protein Kinase C/*metabolism ; Receptor, ErbB-2/metabolism ; }, abstract = {The protein kinase C (PKC) family has been functionally linked to cancer. It has been suggested that atypical PKCs contribute to cell proliferation and cancer progression. With respect to breast cancer, PKCζ has been found to play a key role in intracellular transduction of mitogenic and apoptotic signals using mammary cell lines. However, little is known about its function in vivo. Here we examined the correlation between PKCζ protein levels and important clinicopathologic factors in breast cancer using patient samples. To conduct the study, 30 invasive ductal carcinoma cases and their paired normal tissues were used for tissue microarray analysis (TMA) and 16 were used for western blot analysis. In addition, the correlation between PKCζ expression levels and clinicopathologic characteristics was determined in 176 cases with relevant clinical data. Finally, the correlation between PKCζ and epithelial growth factor receptor 2 (HER2) expressions was determined using three breast cancer cell lines by western blot analysis. Both TMA and western blot results showed that PKCζ protein was highly expressed in primary tumors but not in paired normal tissue. The correlation study indicated that high PKCζ levels were associated with premenopausal patients (p = 0.019) and worse prognostic factors, such as advanced clinical stage, more lymph node involvement and larger tumor size. Both disease-free survival and overall survival rates were lower in the high PKCζ group than those in the low PKCζ group. No correlation was observed between PKCζ levels and age, histological grade, or estrogen or progesterone receptor expression status. A positive correlation between PKCζ and HER2 levels was observed in both tumor samples and cell lines. Our observations link PKCζ expression with factors pointing to worse prognosis, higher HER2 levels and a lower survival rate. This suggests that PKCζ protein levels may serve as a prognostic marker of breast cancer.}, } @article {pmid24600240, year = {2014}, author = {Dupont, E and Journet, M and Oula, ML and Gomez, J and Léveillé, C and Loing, E and Bilodeau, D}, title = {An integral topical gel for cellulite reduction: results from a double-blind, randomized, placebo-controlled evaluation of efficacy.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {7}, number = {}, pages = {73-88}, pmid = {24600240}, issn = {1178-7015}, abstract = {BACKGROUND: Cellulite is a serious cosmetic concern for most of the 90% of women affected by it.

OBJECTIVE: To assess the clinical efficacy of a complex integral anti-cellulite gel.

METHODS: This double-blind, randomized, placebo-controlled study involved 44 healthy women, aged 25-55 years. Subjects had a normal to slightly overweight body mass index and presented slight to moderate cellulite on their thighs, buttocks, and/or hips at baseline. Subjects were randomly assigned to either the treated or placebo group and accordingly applied the active product or placebo on their hips, stomach, buttocks, and thighs, twice daily for 3 months. Skin tonicity, orange-peel aspect, and stubborn cellulite were assessed at day 0, 28, 56, and 84. A self-evaluation questionnaire was completed by all volunteers.

RESULTS: At the end of the study, an average of 81% of the subjects applying the active product presented improvement in their cellulite condition versus 32% for the placebo group (all descriptors and sites combined). At day 84, skin tonicity, orange-peel appearance, and stubborn cellulite were improved in a significant manner (P<0.05) over placebo, on all studied areas. Skin tonicity improved on average by +41% for buttocks, +35% for hips, and +31% for thighs. Orange peel appearance was reduced on average by -25% for buttocks, -22% for hips, and -22% for thighs. Stubborn cellulite was reduced on average by -19% for buttocks, -24% for hips, and -22% for thighs. Circumference measurements decreased in a significant manner (P<0.05) over placebo, for the abdomen (average value of -1.1 cm) and thighs (average value of -0.8 cm). The product was well tolerated and perceived by the volunteers themselves as better performing than placebo on all criteria.

CONCLUSION: All results validate the efficacy of the present integral formulation to significantly reduce signs of cellulite and reshape the silhouette.}, } @article {pmid24596383, year = {2014}, author = {Merdad, A and Karim, S and Schulten, HJ and Dallol, A and Buhmeida, A and Al-Thubaity, F and Gari, MA and Chaudhary, AG and Abuzenadah, AM and Al-Qahtani, MH}, title = {Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis.}, journal = {Anticancer research}, volume = {34}, number = {3}, pages = {1355-1366}, pmid = {24596383}, issn = {1791-7530}, mesh = {Animals ; Apoptosis/*drug effects ; Biomarkers, Tumor/*genetics/metabolism ; Blotting, Western ; Breast Neoplasms/drug therapy/*enzymology/pathology ; Cell Proliferation/drug effects ; Female ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinases/*metabolism ; Mitochondria/drug effects/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Quinuclidines/pharmacology ; RNA, Messenger/genetics ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; beta Catenin/genetics/metabolism ; }, abstract = {BACKGROUND/AIM: Breast cancer (BC) is the most common type of cancer in Saudi women. Matrix metalloproteinases (MMPs) are endopeptidases with the ability to degrade extracellular matrix proteins. In healthy individual tissue disruption is prevented by precised regulation of MMPs; however, in cancer a number of MMPs are overexpressed causing tissue disruption and making tumor cells capable of invasion and metastasis. Invasive ductal carcinoma (IDC) of BCs are classified into grade 1 (G1), grade 2 (G2) and grade 3 (G3) tumors.

MATERIALS AND METHODS: We performed a transcriptomic profiling of 38 surgically-resected breast tumors (4 G1, 17 G2 and 17 G3) using Affymetrix Gene 1.0 ST microarrays. Differentially expressed genes for each grade were identified by the Partek Genomic Suite 6.4 and expression analysis results were validated by immunohistochemistry at the protein level. Pathway analyses and establishment of clinical significance of findings were performed using the appropriate software.

RESULTS: We identified 1,593 differentially expressed genes in BC grades in comparison to normal samples using a cut-off of p<0.05 and fold change >2. Out of these genes 429 were expressed throughout in all grades along with tumor progression while many others associated with specific grades (440 genes in G1, 203 in G2 and 394 in G3 only) were exclusively. Microarray results indicate that mRNA expression of MMP-1, -9,-11,-12, and -13 were up-regulated in higher BC grades when compared to normal breast tissues. MMP-9 was expressed in most IDC (97.5%) samples and was highly expressed in 55% of the tumors. Differential expression of MMP-9 significantly correlated with histological BC grades of (p=0.03) and strongly correlated with overall survival (p=0.08).

CONCLUSION: Gene expression signatures are unique for specific grades. Overexpression of MMPs in higher grades might be associated with BC tumor invasion and metastasis. Therefore, MMPs, and MMP-9 in particular, are reliable candidates for diagnostic biomarker and drug target and further functional analyses have to be performed in order to confirm their role in BC. Our results also suggest the incidence of MMP-9 expression is high in IDC, but it is of limited prognostic value.}, } @article {pmid24595406, year = {2014}, author = {Braun, M and Hasson-Ohayon, I and Hales, S and Zimmermann, C and Rydall, A and Peretz, T and Rodin, G}, title = {Quality of dying and death with cancer in Israel.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {22}, number = {7}, pages = {1973-1980}, pmid = {24595406}, issn = {1433-7339}, mesh = {Aged ; *Attitude to Death ; Caregivers/psychology ; *Death ; Female ; Humans ; Israel ; Male ; Middle Aged ; Neoplasms/*psychology/therapy ; Palliative Care/psychology ; Retrospective Studies ; Socioeconomic Factors ; Surveys and Questionnaires ; Terminal Care/psychology ; }, abstract = {BACKGROUND: The quality of dying and death refers to the evaluation of the final days of life and the moment of death with respect to how it is prepared for, faced and experienced by those with a terminal illness. It includes experience in multiple domains: physical, psychological, social, spiritual or existential, the nature of health care, life closure and death preparation, and the circumstances of death.

AIM: To explore the quality of dying and death in cancer patients in Israel and its relationship to place of death and socio-demographic characteristics of the primary caregivers and the deceased.

DESIGN: Retrospective assessment of the quality of dying and death, based on caregiver responses to the Quality of Dying and Death (QODD) questionnaire (overall score ranges from 0 to 100; higher scores reflect better dying and death experiences) 8 to 10 months after the death.

PARTICIPANTS: Ninety-five caregivers of Jewish cancer patients, most of whom were female spouses or children of the deceased.

RESULTS: Mean QODD score was 57.2 (standard deviation [SD]=15), which is in the low-moderate range. Place of death, gender and age of the caregiver, and age of the deceased, were associated with QODD score.

CONCLUSIONS: This retrospective study in Israel demonstrated that the overall quality of dying and death was regarded as poor by almost half of the caregivers. These findings may reflect the relative lack of specialized palliative care and advance care planning in Israel at the time of this study, which took place between 2006 and 2009. Further research and enhancement of palliative care resources may be needed in Israel and several encouraging recent developments (e.g. staff training and legislation) suggest that such changes are now underway.}, } @article {pmid24586742, year = {2014}, author = {Hung, MH and Liu, CY and Shiau, CY and Hsu, CY and Tsai, YF and Wang, YL and Tai, LC and King, KL and Chao, TC and Chiu, JH and Su, CH and Lo, SS and Tzeng, CH and Shyr, YM and Tseng, LM}, title = {Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e89389}, pmid = {24586742}, issn = {1932-6203}, mesh = {Adult ; Age Factors ; Brain/pathology ; Brain Neoplasms/metabolism/*pathology/*secondary ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk ; Triple Negative Breast Neoplasms/metabolism/*pathology ; }, abstract = {BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis.

RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years.

CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.}, } @article {pmid24585434, year = {2014}, author = {Endo, M and Yamamoto, Y and Nakano, M and Masuda, T and Odagiri, H and Horiguchi, H and Miyata, K and Kadomatsu, T and Motokawa, I and Okada, S and Iwase, H and Oike, Y}, title = {Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis.}, journal = {The International journal of biological markers}, volume = {29}, number = {3}, pages = {e239-45}, doi = {10.5301/jbm.5000080}, pmid = {24585434}, issn = {1724-6008}, mesh = {Adult ; Aged ; Aged, 80 and over ; Angiopoietin-Like Protein 2 ; Angiopoietin-like Proteins ; Angiopoietins/*blood ; Animals ; Breast Neoplasms/*blood/*pathology ; Carcinoma, Ductal, Breast/*blood/*pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation/physiology ; Disease Progression ; Female ; Heterografts ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Metastasis ; Triple Negative Breast Neoplasms/*blood/*pathology ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is a leading cause of cancer-related death in women worldwide, and its metastasis is a major cause of disease mortality. Therefore, identification of the mechanisms underlying breast cancer metastasis is crucial for the development of therapeutic and diagnostic strategies. Our recent study of immunodeficient female mice transplanted with MDA-MB231 breast cancer cells demonstrated that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) accelerates metastasis through both increasing tumor cell migration in an autocrine/paracrine manner, and enhancing tumor angiogenesis. To determine whether ANGPTL2 contributes to its clinical pathogenesis, we asked whether serum ANGPTL2 levels reflect the clinical features of breast cancer progression.

METHODS: We monitored the levels of secreted ANGPTL2 in supernatants of cultured proliferating MDA-MB231 cells. We also determined whether the circulating ANGPTL2 levels were positively correlated with cancer progression in an in vivo breast cancer xenograft model using MDA-MB231 cells. Finally, we investigated whether serum ANGPTL2 levels were associated with clinical features in breast cancer patients.

RESULTS: Both in vitro and in vivo experiments showed that the levels of ANGPTL2 secreted from breast cancer cells increased with cell proliferation and cancer progression. Serum ANGPTL2 levels in patients with metastatic breast cancer were significantly higher than those in healthy subjects or in patients with ductal carcinoma in situ or non-metastatic invasive ductal carcinoma. Serum ANGPTL2 levels in patients negative for estrogen receptors and progesterone receptors, particularly triple-negative cases, reflected histological grades.

CONCLUSIONS: These findings suggest that serum ANGPTL2 levels in breast cancer patients could represent a potential marker of breast cancer metastasis.}, } @article {pmid24583468, year = {2014}, author = {Saguy, T and Halperin, E}, title = {Exposure to Outgroup Members Criticizing Their Own Group Facilitates Intergroup Openness.}, journal = {Personality & social psychology bulletin}, volume = {40}, number = {6}, pages = {791-802}, doi = {10.1177/0146167214525475}, pmid = {24583468}, issn = {1552-7433}, abstract = {A major barrier to conflict resolution is group members' tendency to hold on to the ingroup's narrative of the conflict and reject the outgroup's perspective. In the current research, we propose that voicing internal criticism to an outgroup crowd can undermine such orientations and foster intergroup openness. Across four experiments, Israeli Jews who were exposed to a Palestinian criticizing Palestinians were more open to the Palestinians' perspective of the conflict, than those not exposed to the criticism. This effect was obtained when the criticism was related (Study 1) and unrelated (Study 2) to the conflict, and was consistently mediated by increased hope about the future relations between the groups. Study 3 showed that the effect is more pronounced among those who believe that groups can change. Study 4 established that perceptions about the outgroup as open-minded underlie the effect of ingroup criticism on hope, and further demonstrated downstream effects of openness.}, } @article {pmid24581921, year = {2014}, author = {Hahn, E and Zuckerman, WA and Chen, JM and Singh, RK and Addonizio, LJ and Richmond, ME}, title = {An echocardiographic measurement of superior vena cava to inferior vena cava distance in patients<20 years of age with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {113}, number = {8}, pages = {1405-1408}, doi = {10.1016/j.amjcard.2014.01.416}, pmid = {24581921}, issn = {1879-1913}, mesh = {Adolescent ; Anastomosis, Surgical/methods ; Cardiomyopathy, Dilated/*diagnostic imaging/physiopathology/surgery ; Child ; Child, Preschool ; Echocardiography/*methods ; Female ; Follow-Up Studies ; Heart Atria/*diagnostic imaging/surgery ; Heart Transplantation/methods ; Humans ; Infant ; Male ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Vena Cava, Inferior/*diagnostic imaging/surgery ; Vena Cava, Superior/*diagnostic imaging/surgery ; Ventricular Function, Left ; Young Adult ; }, abstract = {In normal pediatric echocardiograms, the distance from the junction of superior vena cava (SVC) and right atrium to inferior vena cava (IVC) and right atrium is linearly related to height. We examine this relation in children listed for heart transplant with idiopathic dilated cardiomyopathy (IDC) compared with the previously defined normal distribution of SVC-IVC to improve matching of heart sizes. Measurements of SVC-IVC and left ventricular end-diastolic diameter in 55 pediatric patients with IDC were correlated with height, weight, and body surface area. Regression analyses were performed to find the best-fit equation and correlation coefficient. Generalized linear modeling compared SVC-IVC in patients with IDC with normal SVC-IVC values from 254 patients. There was a strong linear relation in patients with IDC between SVC-IVC and height (R2=0.84) and a logarithmic relation to weight (R2=0.80). Left ventricular end-diastolic diameter did not correlate with SVC-IVC or any other parameter. In 87% of patients with IDC, SVC-IVC was over 2 SDs above predicted normal values (mean z-score=4.3±2.1). In conclusion, predicted SVC-IVC in patients with IDC was different from published norms (p<0.001). SVC-IVC in pediatric patients with IDC, although linearly related to height, is consistently above normal values.}, } @article {pmid24581736, year = {2014}, author = {Wei, S and Bleiweiss, IJ and Nagi, C and Jaffer, S}, title = {Characteristics of breast carcinoma cases with false-negative sentinel lymph nodes.}, journal = {Clinical breast cancer}, volume = {14}, number = {4}, pages = {280-284}, doi = {10.1016/j.clbc.2013.12.009}, pmid = {24581736}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Carcinoma, Lobular/*secondary/surgery ; False Negative Reactions ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: In the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses.

PATIENTS AND METHODS: We analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling.

RESULTS: There was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (≥ 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both.

CONCLUSION: False-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.}, } @article {pmid24579390, year = {2013}, author = {Abdus-Salam, AA and Moharson-Bello, IA and Eriba, LO and Abdus-Salam, RA}, title = {Metachronus endometrial carcinoma in a seventy five year old woman with carcinoma of the left breast treated with tamoxifen.}, journal = {African journal of medicine and medical sciences}, volume = {42}, number = {3}, pages = {271-275}, pmid = {24579390}, issn = {0309-3913}, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Endometrial Neoplasms/*drug therapy/pathology ; Female ; Humans ; Neoplasms, Second Primary/*drug therapy/pathology ; Tamoxifen/*therapeutic use ; }, abstract = {BACKGROUND: A second cancer is a different type of cancer than the original cancer. It is diagnosed after a completed treatment for the first cancer. Second cancers occur in only one to three percent of survivors. The level of risk is very small. In general, greater numbers of cancer survivors are living longer due to improvements in treatment. Whether or not a second cancer develops is dependent on many factors. These include the age of the patient when treated, the treatment received, the genetic make-up and family history. The actual number of people who will get a second cancer is relatively small. Each cancer survivor's experience is unique. The aim of this report is to call attention to what might be an emerging place of secondary malignancies in cancer survivors in our setting.

METHOD: We report a case seen in our practice of a seventy five year old woman who was treated for invasive ductal carcinoma of the left breast and developed invasive endometrial carcinoma about 4 years later.

CONCLUSION: There is a need to be on the lookout for possible second malignancies in cancer survivors. Examination and tests for second malignancies should be part of the routine follow up procedures in this group of patients.}, } @article {pmid24577164, year = {2016}, author = {Makhoul, I and Griffin, RJ and Siegel, E and Lee, J and Dhakal, I and Raj, V and Jamshidi-Parsian, A and Klimberg, S and Hutchins, LF and Kadlubar, S}, title = {High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer.}, journal = {American journal of clinical oncology}, volume = {39}, number = {3}, pages = {248-254}, pmid = {24577164}, issn = {1537-453X}, support = {UL1 RR029884/RR/NCRR NIH HHS/United States ; }, mesh = {Angiopoietin-1/blood ; Angiopoietin-2/blood ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Becaplermin ; Bevacizumab/administration & dosage ; Biomarkers, Tumor/blood ; Breast Neoplasms/chemistry/*drug therapy/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Docetaxel ; Doxorubicin/administration & dosage ; Female ; Fibroblast Growth Factor 2/blood ; Humans ; Interleukin-1alpha/blood ; Matrix Metalloproteinase 9/blood ; Neoadjuvant Therapy ; Neovascularization, Pathologic/*drug therapy ; Platelet Endothelial Cell Adhesion Molecule-1/blood ; Platelet-Derived Growth Factor/metabolism ; Prospective Studies ; Proto-Oncogene Proteins c-sis/blood ; Receptor, ErbB-2/analysis ; Receptor, TIE-2/*blood ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Taxoids/administration & dosage ; Vascular Endothelial Growth Factor A/blood ; Vascular Endothelial Growth Factor Receptor-2/blood ; }, abstract = {INTRODUCTION: Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has been marked by the development of the monoclonal antibody bevacizumab, which targets VEGF in many solid tumors. As patients do not equally benefit from bevacizumab, it has become necessary to define the profile of patients who will benefit from the drug.

MATERIALS AND METHODS: We have conducted a prospective phase II study in 39 patients using bevacizumab in breast cancer in the neoadjuvant setting, and found improved pathologic complete response (pCR) when bevacizumab was added to chemotherapy in patients with hormone receptor negative and invasive ductal carcinoma. Blood samples were collected at baseline and serially while patients were on treatment. Circulating angiogenesis-related proteins angiopoietin (ANG)1, ANG2, basic fibroblast growth factor, IL-1a, matrix metalloproteinase 9, platelet derived growth factor - BB, platelet endothelial cell adhesion molecule -1, Tie2, VEGF, and vascular endothelial growth factor receptor 2 were measured at baseline and during treatment. This correlative study was conducted to identify specific serum angiogenic factor profiles that might be associated with pCR in the neoadjuvant setting in breast cancer patients receiving bevacizumab and chemotherapy.

RESULTS: Elevated baseline serum Tie2 and basic fibroblast growth factor were associated with pCR in response to this combination. Changes in serum levels of these proteins were seen during treatment but were not significantly different between the pCR and non-pCR groups.

CONCLUSIONS: Baseline-circulating Tie2 levels may help distinguish patients who will have pCR from those who will not and may form the basis for future development of antiangiogenic therapy in breast cancer. Larger studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT00203502.}, } @article {pmid24574467, year = {2014}, author = {Starmer, HM and Liu, Z and Akst, LM and Gourin, C}, title = {Attendance in voice therapy: can an interdisciplinary care model have an impact?.}, journal = {The Annals of otology, rhinology, and laryngology}, volume = {123}, number = {2}, pages = {117-123}, doi = {10.1177/0003489414523708}, pmid = {24574467}, issn = {0003-4894}, mesh = {Adult ; Aged ; Dysphonia/etiology/*rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Otolaryngology/*statistics & numerical data ; Patient Compliance/*statistics & numerical data ; Referral and Consultation/*statistics & numerical data ; Retrospective Studies ; Speech-Language Pathology/*statistics & numerical data ; Treatment Outcome ; *Voice Training ; Young Adult ; }, abstract = {OBJECTIVES: We sought to determine the effect of referral patterns on attendance in voice therapy.

METHODS: Patients who were seen by a laryngologist for vocal concerns and referred for voice therapy comprised the study population. Outcomes were compared between those who were initially evaluated through the interdisciplinary voice clinic (IDC), which combined speech-language pathology and laryngology care, and those who were evaluated by a laryngologist alone. Adherence was measured by completion of the plan of care.

RESULTS: There were 79 patients evaluated through the IDC and 100 patients evaluated initially by a laryngologist. Patients evaluated through the IDC had more visits with the speech-language pathologist (mean, 3.1 versus 1.24; p < 0.0001). Those initially evaluated through the IDC were more likely to complete their plan of care (p = 0.02). Completion of voice therapy was significantly more likely for individuals coded as being of "other" race (odds ratio, 7.98; p = 0.002) and for patients who participated in the IDC (odds ratio, 2.56; p = 0.018). The cause of dysphonia, sex, marital status, insurance status, days from laryngology referral to the initial speech-language pathologist consultation, the initial Voice-Related Quality of Life score, and distance to the clinic were not associated with patient attendance.

CONCLUSIONS: Patients evaluated in a coordinated IDC should be more likely to attend voice therapy and complete their plan of care, regardless of other factors.}, } @article {pmid24574065, year = {2014}, author = {Kwon, SY and Lee, JH and Kim, B and Park, JW and Kwon, TK and Kang, SH and Kim, S}, title = {Complexity in regulation of microRNA machinery components in invasive breast carcinoma.}, journal = {Pathology oncology research : POR}, volume = {20}, number = {3}, pages = {697-705}, pmid = {24574065}, issn = {1532-2807}, mesh = {Argonaute Proteins/*genetics/metabolism ; Breast/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; DEAD-box RNA Helicases/*genetics/metabolism ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; MicroRNAs/*genetics ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Proteins/*genetics/metabolism ; RNA, Messenger/genetics ; RNA-Binding Proteins ; Real-Time Polymerase Chain Reaction ; Ribonuclease III/*genetics/metabolism ; }, abstract = {Altered expression of microRNA (miRNA) machinery components may play an important role in breast cancer progression. The objective of the current study was to evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to assess the value of clinical parameters on their expression. By using quantitative real-time PCR, we examined the expression of the four miRNA machinery components in 52 breast tumor tissues which are diagnosed as invasive ductal carcinoma and adjacent non-neoplastic tissues. In the present study, decreased mRNA expression levels of major miRNA machinery components were observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are positively correlated with to each other. This study revealed for the first time that expression alterations of DGCR8 are significantly associated with estrogen receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was significantly correlated with N stage. These results provided evidences that down-regulated the four miRNA machinery components may play an important role in breast pathobiology and that DGCR8 and AGO2 might be associated with important clinical factors.}, } @article {pmid24572007, year = {2014}, author = {Mbunda, T and Bakari, M and Tarimo, EA and Sandstrom, E and Kulane, A}, title = {Factors that influence the willingness of young adults in Dar es Salaam, Tanzania, to participate in phase I/II HIV vaccine trials.}, journal = {Global health action}, volume = {7}, number = {}, pages = {22853}, pmid = {24572007}, issn = {1654-9880}, mesh = {AIDS Vaccines/*therapeutic use ; Adolescent ; Adult ; Attitude to Health ; Clinical Trials, Phase I as Topic/*statistics & numerical data ; Clinical Trials, Phase II as Topic/*statistics & numerical data ; Female ; HIV Infections/*prevention & control ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Research Subjects/*psychology ; Sexual Behavior/statistics & numerical data ; Surveys and Questionnaires ; Tanzania/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: HIV/AIDS continues to destroy the lives of young people especially in low-income countries. The inclusion of youths in HIV vaccine trials is of utmost importance in obtaining an effective vaccine that is acceptable to them.

OBJECTIVE: To characterize the willingness of young adults in Tanzania to participate in an HIV vaccine trial and the factors that influence this willingness.

DESIGN: Four hundred and fifty young adults who visited a youth-friendly Infectious Diseases Clinic (IDC) from February 2012 to September 2012 completed a self-administered questionnaire concerning sociodemographic information, their knowledge about and perception of HIV vaccine studies, and the availability of social support.

RESULT: Of our participants, 50.6% expressed willingness to participate in HIV vaccine trials, and this willingness was positively correlated with having some knowledge about HIV vaccine studies (AOR, 2.2; 95% CI: 1.4-3.4), a positive perception toward such studies (AOR, 2.3; 95% CI: 1.5-3.6), having a relationship with someone who could help them make a decision (AOR, 2.5; 95% CI: 1.3-4.9), and age at the time of sexual debut (AOR, 2.6; 95% CI 1.0-6.7) for 15- to 19-year-olds and (AOR, 2.7; 95% CI 1.0-7.1) for older participants.

CONCLUSION: The participants exhibited a moderate willingness to participate in HIV vaccine trials, which was associated with a positive perception of and some knowledge about such trials, having a relationship with someone who might influence their decision as well as age at time of sexual debut. More efforts should be made to inform the youths about specific HIV vaccine trials and related matters, as well as to engage significant others in the decision-making process.}, } @article {pmid24571647, year = {2014}, author = {Rodrigues Dos Santos, C and Fonseca, I and Dias, S and Mendes de Almeida, JC}, title = {Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {132}, pmid = {24571647}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/mortality/*pathology ; Cholesterol, LDL/*blood ; Disease Progression ; Female ; Humans ; Lipids/blood ; Lipoproteins/blood ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood.

METHODS: Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis.

RESULTS: Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile.

CONCLUSIONS: This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.}, } @article {pmid24559611, year = {2014}, author = {Dieterich, M and Hartwig, F and Stubert, J and Klöcking, S and Kundt, G and Stengel, B and Reimer, T and Gerber, B}, title = {Accompanying DCIS in breast cancer patients with invasive ductal carcinoma is predictive of improved local recurrence-free survival.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {4}, pages = {346-351}, doi = {10.1016/j.breast.2014.01.015}, pmid = {24559611}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; *Mastectomy ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/*pathology ; Neoplasms, Multiple Primary/*pathology/surgery ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) often accompanies invasive ductal carcinoma (IDC). The presence of co-existing DCIS is postulated to present as a less aggressive phenotype than IDC alone.

PATIENTS AND METHODS: Patients diagnosed with hormone receptor-positive breast cancer receiving mastectomy were evaluated. Only patients without adjuvant radio- and chemotherapy were included to decrease treatment bias on local recurrence (LR).

RESULTS: Of 2239 breast cancer patients, 198 fulfilled the inclusion criteria. The overall LR rate was 11.6%. Tumor stage (p = 0.002), nodal status (pN2 vs. pN0, p = 0.023) and pure IDC compared with IDC-DCIS (p = 0.029) were multivariate independent factors for increased LR risk. Patients with IDC-DCIS were significantly younger (p < 0.001), had smaller tumors (p = 0.001), less lymph node involvement (p = 0.012). The LR rate was significantly increased in patients with pure IDC (p = 0.012). The time to distant metastases was decreased in patients with pure IDC compared with that observed in patients with IDC-DCIS (log rank = 0.030).

CONCLUSION: Invasive ductal carcinoma accompanied by DCIS is associated with lower LR. The prognostic value of co-existing DCIS in the adjuvant decision-making process may be considered a new independent prognostic marker. This finding needs further studies to evaluate its usefulness in premenopausal women.}, } @article {pmid24559473, year = {2014}, author = {Siegel, TN and Hon, CC and Zhang, Q and Lopez-Rubio, JJ and Scheidig-Benatar, C and Martins, RM and Sismeiro, O and Coppée, JY and Scherf, A}, title = {Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {150}, pmid = {24559473}, issn = {1471-2164}, support = {250320/ERC_/European Research Council/International ; }, mesh = {3' Untranslated Regions ; Cell Nucleus/metabolism ; Cluster Analysis ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Library ; High-Throughput Nucleotide Sequencing ; Plasmodium falciparum/*genetics ; Polyadenylation ; RNA Splicing ; *RNA, Antisense ; RNA, Messenger/genetics/metabolism ; *RNA, Protozoan ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Advances in high-throughput sequencing have led to the discovery of widespread transcription of natural antisense transcripts (NATs) in a large number of organisms, where these transcripts have been shown to play important roles in the regulation of gene expression. Likewise, the existence of NATs has been observed in Plasmodium but our understanding towards their genome-wide distribution remains incomplete due to the limited depth and uncertainties in the level of strand specificity of previous datasets.

RESULTS: To gain insights into the genome-wide distribution of NATs in P. falciparum, we performed RNA-ligation based strand-specific RNA sequencing at unprecedented depth. Our data indicate that 78.3% of the genome is transcribed during blood-stage development. Moreover, our analysis reveals significant levels of antisense transcription from at least 24% of protein-coding genes and that while expression levels of NATs change during the intraerythrocytic developmental cycle (IDC), they do not correlate with the corresponding mRNA levels. Interestingly, antisense transcription is not evenly distributed across coding regions (CDSs) but strongly clustered towards the 3'-end of CDSs. Furthermore, for a significant subset of NATs, transcript levels correlate with mRNA levels of neighboring genes.Finally, we were able to identify the polyadenylation sites (PASs) for a subset of NATs, demonstrating that at least some NATs are polyadenylated. We also mapped the PASs of 3443 coding genes, yielding an average 3' untranslated region length of 523 bp.

CONCLUSIONS: Our strand-specific analysis of the P. falciparum transcriptome expands and strengthens the existing body of evidence that antisense transcription is a substantial phenomenon in P. falciparum. For a subset of neighboring genes we find that sense and antisense transcript levels are intricately linked while other NATs appear to be regulated independently of mRNA transcription. Our deep strand-specific dataset will provide a valuable resource for the precise determination of expression levels as it separates sense from antisense transcript levels, which we find to often significantly differ. In addition, the extensive novel data on 3' UTR length will allow others to perform searches for regulatory motifs in the UTRs and help understand post-translational regulation in P. falciparum.}, } @article {pmid24551675, year = {2013}, author = {M, Y and Ahmadi M R, H and J, K and H, P and K H, A and M R, Y and K, H}, title = {An 8 years retrospective study of breast cancer incidence in ilam province, Western iran.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {7}, number = {12}, pages = {2923-2925}, pmid = {24551675}, issn = {2249-782X}, abstract = {INTRODUCTION: Breast cancer is the most common cancer (27% of all cancers) and common cause of death (16%) which occurs due to cancers among women, either in developed or developing countries. The current study aimed to assess incidence of breast cancer in west of Iran (Ilam province).

METHODS: During a cross-sectional study, all documented records of patients who were referred to the health centre of Ilam province in a period of 8 years (2002-2009) were investigated and 82 files which were related to breast cancer were identified. Patients' data were entered into SPSS, version 16 and using X2, t-test and descriptive statistics, they were analyzed.

RESULTS: Totally, 82 confirmed breast cancer cases were diagnosed between 2002-2009 and this figure accounted for 21.4% of all cancers in Ilam province. The mean age with standard deviation (SD) of patients was 47.4 ± 14.5 years and the disease was most frequent in the age group of 30-40 years (38.3%). The highest incidence rate was seen in 2006- 2007 and the lowest rate was seen in 2002-2003. The most prevalent morphologic pattern of breast caner (86.2%) was invasive ductal carcinoma (IDC). There was a 23% incidence rate for breast cancer, with a significant increase in its incidence rate during 2002-2009.

CONCLUSION: Due to diagnosis of the disease in its advanced stages, and also involvement of low age groups and young population in the country, screening programs such as self examination, examination by doctors and mammography should be started in the lower age groups, in ages which are lower than 30 years.}, } @article {pmid24551288, year = {2014}, author = {Zhao, H and Chen, D and Wang, J and Yin, Y and Gao, Q and Zhang, Y}, title = {Downregulation of the transcription factor, FoxD3, is associated with lymph node metastases in invasive ductal carcinomas of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {7}, number = {2}, pages = {670-676}, pmid = {24551288}, issn = {1936-2625}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/secondary ; Case-Control Studies ; Down-Regulation ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis ; MCF-7 Cells ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/genetics/*metabolism/pathology ; }, abstract = {FoxD3 is a transcription factor of the forkhead gene family. We investigated its expression in invasive ductal carcinomas (IDC) of the breast and its association with metastasis. The expression of FoxD3, human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), progesterone receptor (PR) and Ki67 was examined by immunohistochemistry in samples from 121 patients with IDC. Non-tumorous breast adenosis tissues served as controls. HER2 expression was confirmed by fluorescence in situ hybridization (FISH). The expression levels of FoxD3 in IDC tissues and the breast cancer cell lines MCF-7 and MDA-MB-231 were additionally measured by western blotting. A greater percentage of total IDC patients and patients with lymph node metastases showed reduced FoxD3 expression compared to adenosis controls (p<0.05). Overall, FoxD3 was associated with metastatic status of IDC but not with age, pathological or clinical staging, or status of HER-2, ER, or PR. In particular, FoxD3 protein expression was down-regulated in the tumor epithelia of IDC samples from patients with metastases. Furthermore, FoxD3 protein expression was decreased in the metastatic MDA-MB-231 breast cancer cell line relative to the non-metastatic cell line, MCF-7. A greater number of patients with invasive, triple-negative breast cancer were also negative for FoxD3 expression than in other, non-triple-negative tumor types. These results suggest an inverse relationship between FoxD3 expression and tumor metastasis and warrants further investigation.}, } @article {pmid24548706, year = {2014}, author = {Thorner, DA and Blaivas, JG and Tsui, JF and Kashan, MY and Weinberger, JM and Weiss, JP}, title = {Outcomes of reduction cystoplasty in men with impaired detrusor contractility.}, journal = {Urology}, volume = {83}, number = {4}, pages = {882-886}, doi = {10.1016/j.urology.2013.10.068}, pmid = {24548706}, issn = {1527-9995}, mesh = {Adult ; Aged ; Cystoscopy/methods ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle Contraction ; Muscle, Smooth/*pathology ; Postoperative Period ; Prostatectomy/methods ; Retrospective Studies ; Treatment Outcome ; Urinary Bladder/*surgery ; Urinary Bladder Neck Obstruction/*surgery ; Urinary Catheterization ; Urodynamics ; Urologic Surgical Procedures ; }, abstract = {OBJECTIVE: To report surgical outcomes in patients with impaired detrusor contractility (IDC) treated with reduction cystoplasty (RC).

METHODS: This was a retrospective study of consecutive patients with IDC who underwent RC. IDC was defined as a bladder contractility index of <100 and/or a detrusor contraction of insufficient duration resulting in a postvoid residual volume (PVR) >600 mL. Bladder outlet obstruction was defined by a bladder outlet obstruction index (BOOI) >40. All patients had preoperative International Prostate Symptom Score, maximum uroflow (Qmax), PVR, bladder diary, videourodynamics, and cystoscopy. Patients with prostatic obstruction underwent synchronous open prostatectomy. Postoperative Qmax, PVR, need for clean intermittent catheterization (CIC), and Patient Global Impression of Improvement (PGII) score were obtained. Follow-up was at 3 months, 1 year, and yearly thereafter.

RESULTS: Eight men met inclusion criteria (mean age, 60; range, 43-75 years). Preoperatively, 3 of 8 patients (37.5%) had moderate-sized bladder diverticula, 4 of 8 (50%) had a bladder contractility index <100, and 6 of 8 (75%) had a BOOI <40. Two patients (25%) fulfilled criteria for bladder outlet obstruction (BOOI, 67 and 72). Three (37.5%) underwent synchronous bladder diverticulectomy, and 3 (37.5%) underwent suprapubic prostatectomy. All patients were available for follow-up at 1 year. Seven of 8 (88%) had a successful outcome (PGII ≤2). One patient was unchanged (PGII, 4) and still needed CIC.

CONCLUSION: All but 1 patient who met specific criteria for RC had excellent outcomes after surgery based on the PGII, PVR, Qmax, and need for CIC. RC is a viable option for properly selected patients with IDC.}, } @article {pmid24535908, year = {2014}, author = {Oliveira, AL and Oliveira Rodrigues, FF and Dos Santos, RE and Rozenowicz, RL and Barbosa de Melo, M}, title = {GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {13}, number = {2}, pages = {2521-2530}, doi = {10.4238/2014.January.22.9}, pmid = {24535908}, issn = {1676-5680}, mesh = {Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Breast Neoplasms/drug therapy/*genetics/pathology ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi/*genetics ; Glutathione Transferase/*genetics ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Polymorphism, Single Nucleotide ; Prognosis ; }, abstract = {The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the post-therapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wild-type or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.}, } @article {pmid24530247, year = {2014}, author = {Chen, TD and Lee, LY}, title = {A case of renal cell carcinoma metastasizing to invasive ductal breast carcinoma.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {113}, number = {2}, pages = {133-136}, doi = {10.1016/j.jfma.2012.07.022}, pmid = {24530247}, issn = {0929-6646}, mesh = {Aged ; Breast Neoplasms/*pathology/*secondary ; Carcinoma, Ductal/*pathology/*secondary ; Carcinoma, Renal Cell/*pathology ; Female ; Humans ; Kidney Neoplasms/*pathology ; }, abstract = {Tumor-to-tumor metastasis is an uncommon but well-documented phenomenon. We present a case of a clear cell renal cell carcinoma (RCC) metastasizing to an invasive ductal carcinoma (IDC) of the breast. A 74-year-old woman with a past history of clear cell RCC status after radical nephrectomy underwent right modified radical mastectomy for an enlarging breast mass 3 years after nephrectomy. Histological examination revealed a small focus with distinct morphological features similar to clear cell RCC encased in the otherwise typical IDC. Immunohistochemical studies showed that this focus was positive for CD10 and vimentin, in contrast to the surrounding IDC, which was negative for both markers and positive for Her2/neu. Based on the histological and immunohistochemical features, the patient was diagnosed with metastasis of clear cell RCC to the breast IDC. To the best of our knowledge, this is the first reported case of a breast neoplasm as the recipient tumor in tumor-to-tumor metastasis.}, } @article {pmid24530094, year = {2014}, author = {Brouckaert, O and Laenen, A and Smeets, A and Christiaens, MR and Vergote, I and Wildiers, H and Moerman, P and Floris, G and Neven, P and , }, title = {Prognostic implications of lobular breast cancer histology: new insights from a single hospital cross-sectional study and SEER data.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {4}, pages = {371-377}, doi = {10.1016/j.breast.2014.01.007}, pmid = {24530094}, issn = {1532-3080}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Neoplasm Staging ; Prognosis ; SEER Program ; Statistics as Topic ; Time Factors ; }, abstract = {BACKGROUND: Invasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC.

METHODS: Primary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation.

RESULTS: In lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380-7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309-0.703), p = 0.0003) and BCSS (HR 0.441 (0.247-0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4-5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown).

CONCLUSION: The prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority (= node negative) of ILCs.}, } @article {pmid24527724, year = {2015}, author = {Nakash, O and Nagar, M and Levav, I}, title = {Predictors of mental health care stigma and its association with the therapeutic alliance during the initial intake session.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {25}, number = {2}, pages = {214-221}, doi = {10.1080/10503307.2014.885147}, pmid = {24527724}, issn = {1468-4381}, mesh = {Adult ; Humans ; Mental Health Services/*standards ; Mentally Ill Persons/*psychology ; *Professional-Patient Relations ; Psychotherapy/*standards ; *Social Stigma ; }, abstract = {OBJECTIVE: We investigated the association between socio-demographic and clinical variables with mental health care stigma, and the impact of the latter on the quality of the therapeutic alliance measured at intake.

METHOD: Consecutive clients (N = 236) filled questionnaires upon accessing services for a new episode of care. Immediately following the intake, a randomly selected sample of clients and their corresponding therapists (n = 102) completed the Working Alliance Inventory - Bond Scale.

RESULTS: Lower mean years of education and higher emotional distress (both partial r = .17) were significantly associated with higher stigma. Higher care stigma negatively correlated with therapists' ratings of the therapeutic alliance during the intake (partial r = -.22), but not with those of clients.

CONCLUSIONS: Care stigma is present among service-users and may affect outcomes of the intake.}, } @article {pmid24527079, year = {2014}, author = {Calaf, GM and Balajee, AS and Montalvo-Villagra, MT and Leon, M and Daniela, NM and Alvarez, RG and Roy, D and Narayan, G and Abarca-Quinones, J}, title = {Vimentin and Notch as biomarkers for breast cancer progression.}, journal = {Oncology letters}, volume = {7}, number = {3}, pages = {721-727}, pmid = {24527079}, issn = {1792-1074}, abstract = {Breast cancer, the most common spontaneous malignancy diagnosed in women, is a classical model of hormone dependency as it is associated with prolonged exposure to female hormones. Different cytoplasmic proteins are important in the transformation of a normal cell to an invasive tumor cell, and these include vimentin and Notch. To investigate the importance of these two genes and proteins in breast carcinogenesis, we used an in vitro breast cancer model system, in which an immortalized human breast epithelial cell line, MCF-10F, was malignantly transformed by exposure to low doses of high linear energy transfer α particle (150 keV/μm) radiation and subsequent growth in the presence or absence of 17β-estradiol. This model consisted of human breast epithelial cells in different stages of transformation: i) a parental cell line (MCF-10F), ii) an Estrogen cell line (MCF-l0F continuously grown with estradiol at 10[-8]), iii) a malignant and non-tumorigenic cell line (Alpha3), iv) a malignant and tumorigenic cell line (Alpha5) and v) a Tumor2 cell line derived from a xenograft of the Alpha5 cell line injected into nude mice. Vimentin and Notch showed greater expression in the Alpha5 and Tumor2 cell lines compared with that in the non-tumorigenic cell lines, MCF-10F, Estrogen and Alpha3. In the present study, positive staining for vimentin was found in 21% of cases. Vimentin and Notch protein expression was negative in noninvasive ductal carcinoma biopsies from breast cancer patients. However, positive cell expression was observed in invasive ductal carcinoma biopsies. These biomarkers can be considered important indicators of breast cancer progression and can be added to the diagnostic panel when overall survival is a primary end-point.}, } @article {pmid24526754, year = {2015}, author = {Mennella, S and Garlaschi, A and Paparo, F and Perillo, M and Celenza, M and Massa, T and Rollandi, GA and Garlaschi, G}, title = {Magnetic resonance imaging of breast cancer: factors affecting the accuracy of preoperative lesion sizing.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {56}, number = {3}, pages = {260-268}, doi = {10.1177/0284185114524089}, pmid = {24526754}, issn = {1600-0455}, mesh = {Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Observer Variation ; Preoperative Care/*methods ; Reproducibility of Results ; Retrospective Studies ; *Tumor Burden ; }, abstract = {BACKGROUND: Accurate preoperative sizing of breast cancer with imaging modalities has a great importance in the surgical planning.

PURPOSE: To assess the influence of tumor size and histology on the accuracy of measurement of cancer local extension by magnetic resonance imaging (MRI).

MATERIAL AND METHODS: One hundred and eighty-six patients with primary breast cancer, for a total of 221 lesions, were included in this retrospective study. Tumors were divided into five histological groups: invasive ductal carcinoma (IDC), IDC with extensive intraductal component (EIC), invasive lobular carcinoma (ILC), ductal carcinoma in situ (DCIS), and "other histology" (mucinous, papillary, medullary, tubular, and apocrine breast cancer). Microscopic measurement of the largest diameter of tumors at pathology was chosen as reference standard and compared with MRI measurement. Concordance was defined as a difference ≤ 5 mm between MRI and pathology.

RESULTS: The mean size of tumors at pathology was 24.8 ± 19.4 mm, while at MRI it was 29.7 ± 20 mm (P < 0.05), with a significant overestimation of MRI. MRI-pathology concordance was found in 98/221 cases (44.3%), while MRI overestimated the size of 81/221 tumors (36.7%). The extent of overestimation was significantly different among the five histological groups (P < 0.05). At multivariate analysis, DCIS histology was the factor more significantly associated with MRI-pathology discordance (P = 0.0005), while the influence of tumor dimension at pathology was less significant (P = 0.0073).

CONCLUSION: DCIS histology is strongly associated with discordance between MRI and pathology sizing of breast cancer. Lesion size can also influence the accuracy of MRI measurements, but to a lesser extent.}, } @article {pmid24525508, year = {2014}, author = {Boulos, FI and Granja, NM and Simpson, JF and O'Malley, FP and Saadeldine, MM and Page, DL and Sanders, ME}, title = {Intranodal papillary epithelial proliferations: a local process with a spectrum of morphologies and frequent association with papillomas in the breast.}, journal = {The American journal of surgical pathology}, volume = {38}, number = {3}, pages = {383-388}, doi = {10.1097/PAS.0000000000000115}, pmid = {24525508}, issn = {1532-0979}, mesh = {Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology ; Breast Neoplasms, Male/pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; *Cell Proliferation ; Diagnostic Errors/prevention & control ; Epithelial Cells/*pathology ; Female ; Humans ; Hyperplasia ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Papilloma/*pathology ; Predictive Value of Tests ; }, abstract = {Lymph nodes, particularly those draining in major anatomic sites like axilla, pelvis, and neck are potential sites for the occasional presence of ectopic tissue, usually representative of the organ being drained. Owing to the uncertainty surrounding the processes causing such findings, and particularly in the setting of lymph node dissection and sampling for cancer staging, intranodal epithelial inclusions, rare as they may be, might be fertile soil for overdiagnosis of metastatic disease. Intranodal papillary inclusions are particularly problematic and challenging because of their complex architecture that may easily mimic a metastasis. From the files of the Breast Consultation Service, Department of Pathology at the Vanderbilt University Medical Center in Nashville, we identified 6 cases in which histopathologic examination of axillary lymph nodes revealed intranodal papillary inclusions (papillary epithelial proliferations). One case showed atypical ductal hyperplasia, 1 showed low-grade ductal carcinoma in situ, and 1 showed usual ductal hyperplasia. The corresponding breast lesions were papillomas in 5 of 6 cases, 2 of which displayed atypical ductal hyperplasia, whereas 3 showed low-grade ductal carcinoma in situ. One case showed intermediate-grade invasive ductal carcinoma, and the associated intranodal papilloma lacked atypia. Our findings suggest that intranodal papillary proliferations are often, although not exclusively, associated with papillary and noninvasive breast neoplasms, hence highlighting the origin of these intranodal lesions as independent de novo nodal processes rather than metastatic deposits.}, } @article {pmid24525089, year = {2014}, author = {Jalaguier-Coudray, A and Thomassin-Piana, J}, title = {Solid masses: what are the underlying histopathological lesions?.}, journal = {Diagnostic and interventional imaging}, volume = {95}, number = {2}, pages = {153-168}, doi = {10.1016/j.diii.2013.12.014}, pmid = {24525089}, issn = {2211-5684}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; Fibroadenoma/diagnostic imaging/pathology ; Humans ; Ultrasonography ; }, abstract = {The ultrasound signs of breast masses are explained by the histopathological data. Ultrasound masses are classified according to their shape and margin. Round or oval masses are benign when their margins are circumscribed (fibroadenoma, intramammary lymph node); on the other hand, with non-circumscribed margins (microlobulated or irregular), masses that are round or oval may be cancers. Seven histological types of round cancers have been identified: grade III invasive ductal carcinoma, colloid or mucinous carcinoma, medullary carcinoma, intramammary metastases, intracystic papillary carcinoma, lymphoma and high-grade phyllodes tumors. Irregularly shaped ultrasound masses with non-circumscribed margins are predominantly cancers but may in some cases be benign lesions such as sclerosing adenosis, a radial scar, fibroadenoma or phyllodes tumor.}, } @article {pmid24523870, year = {2014}, author = {Blancato, J and Graves, A and Rashidi, B and Moroni, M and Tchobe, L and Ozdemirli, M and Kallakury, B and Makambi, KH and Marian, C and Mueller, SC}, title = {SYK allelic loss and the role of Syk-regulated genes in breast cancer survival.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e87610}, pmid = {24523870}, issn = {1932-6203}, support = {9R01 CA112673/CA/NCI NIH HHS/United States ; 1 S10 RR019291-01A2/RR/NCRR NIH HHS/United States ; 2P30-CA-51008/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA112673/CA/NCI NIH HHS/United States ; U56 CA101563/CA/NCI NIH HHS/United States ; 1S10RR15768-01/RR/NCRR NIH HHS/United States ; S10 RR019291/RR/NCRR NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*metabolism/mortality ; Carcinoma, Ductal, Breast/*genetics/*metabolism/mortality ; Chromosome Mapping ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; In Situ Hybridization, Fluorescence ; Intracellular Signaling Peptides and Proteins/*genetics ; Kaplan-Meier Estimate ; *Loss of Heterozygosity ; Neoplasm Invasiveness ; Prognosis ; Promoter Regions, Genetic ; Protein-Tyrosine Kinases/*genetics ; Syk Kinase ; Treatment Outcome ; }, abstract = {Heterozygotic loss of SYK, a non-receptor tyrosine kinase, gives rise to mouse mammary tumor formation where Syk protein levels are reduced by about half; loss of SYK mRNA is correlated with invasive cell behavior in in vitro models; and SYK loss has been correlated with distant metastases in patients. Here, allelic loss of the SYK gene was explored in breast ductal carcinoma in situ (DCIS) using fluorescence in situ hybridization and pyrosequencing, respectively, and in infiltrating ductal carcinoma (IDC) using genomic data from The Cancer Genome Atlas (TCGA). Allelic loss was present in a subset of DCIS cases where adjacent IDC was present. SYK copy number loss was found in about 26% of 1002 total breast cancer cases and 30% of IDC cases. Quantitative immunofluorescence revealed Syk protein to be six-fold higher in infiltrating immune cells compared with epithelial cells. This difference distorted tumor cell mRNA and protein levels in extracts. 20% of 1002 IDC cases contained elevated immune cell infiltration as estimated by elevated immune-specific mRNAs. In cases without immune cell infiltration, loss of SYK copy number was associated with a significant reduction of SYK mRNA. Here we define a 55 Gene Set consisting of Syk interacting, motility- and invasion-related genes. We found that overall survival was significantly reduced in IDC and Luminal A+B cases where copy number and mutations of these 55 genes were affected (Kaplan-Meier, Logrank test p-value 0.007141 and Logrank test p-value 0.001198, respectively). We conclude that reduction in Syk expression and contributions of genomic instability to copy number and mutations in the 55 Syk interacting genes significantly contribute to poorer overall patient survival. A closer examination of the role of Syk interacting motility and invasion genes and their prognostic and/or causative association with metastatic disease and patient outcome is warranted.}, } @article {pmid24523791, year = {2013}, author = {Mohammadizadeh, F and Hani, M and Ranaee, M and Bagheri, M}, title = {Role of cyclin D1 in breast carcinoma.}, journal = {Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences}, volume = {18}, number = {12}, pages = {1021-1025}, pmid = {24523791}, issn = {1735-1995}, abstract = {BACKGROUND: Breast carcinoma is the most frequent cancer among women with considerable invasive and metastatic behavior. CCND1, the oncogene encoding cyclin D1, is amplified in a substantial proportion of human cancers. Although cyclin D1 overexpression has been reported in up to 50% of human breast cancers, its prognostic impact on breast carcinoma is still controversial.

MATERIALS AND METHODS: In this cross-sectional investigation, 89 patients with breast invasive ductal carcinoma enrolled in the study. Tumor tissue samples were stained immunohistochemically for cyclin D1. The marker was semiquantitatively scored using the Allred scoring method and its relationship with ER, PR, and HER2-neu status as well as age, tumor grade and stage was then determined.

RESULTS: Cyclin D1 was strong (S), intermediate (I), weak (W), and negative (N) in 19.1%, 44.9%, 14.6%, and 21.3% of the cases, respectively. Estrogen receptor (ER), progesterone receptor (PR), and HER2- neu were positive in 60.7%, 58.4%, and 36% of the cases, respectively. There was a statistically significant reverse relationship between tumor grade and cyclin D1 (P = 0.009). The relationship between cyclin D1 and both hormone receptors was also statistically significant (P = 0.0001). There was no statistically significant relationship between cyclin D1 on one hand and age, stage, and HER2-neu on the other (P > 0.05).

CONCLUSION: The reverse relationship between cyclin D1 overexpression and tumor grade as well as its positive relationship with ER and PR in invasive ductal carcinoma suggest that cyclin D1 may directly or indirectly result in maturation and differentiation of tumor cells.}, } @article {pmid24522150, year = {2014}, author = {Keul, C and Stawarczyk, B and Erdelt, KJ and Beuer, F and Edelhoff, D and Güth, JF}, title = {Fit of 4-unit FDPs made of zirconia and CoCr-alloy after chairside and labside digitalization--a laboratory study.}, journal = {Dental materials : official publication of the Academy of Dental Materials}, volume = {30}, number = {4}, pages = {400-407}, doi = {10.1016/j.dental.2014.01.006}, pmid = {24522150}, issn = {1879-0097}, mesh = {Chromium/chemistry ; Cobalt/chemistry ; *Computer-Aided Design ; Dental Alloys/chemistry ; *Denture Design ; *Denture, Partial, Fixed ; Materials Testing ; Models, Dental ; Surface Properties ; Titanium/chemistry ; Tomography, X-Ray Computed ; Zirconium/chemistry ; }, abstract = {OBJECTIVES: To analyse the marginal fit of 4-unit fixed dental prostheses (FDPs) and the accuracy of three-dimensional cast-datasets using both approaches to Computer Aided Design (CAD)/Computer Aided Manufacturing (CAM): direct and indirect digitalization.

METHODS: A titanium model of a 4-unit FDP was digitized by an intraoral scanning device (iTero, Align Technology, Carlstadt, US; DD, n=12). Additionally 12 conventional impressions were taken and referring master casts were digitized by a laboratory scanner (CS2, Straumann, Basel, Switzerland; ID, n=12). Frameworks were fabricated (CARES CADCAM GmbH, Straumann, Markkleeberg, Germany) from base metal alloy (coron, Straumann; DD-C: n=12; ID-C: n=12) and zirconia (zerion, Straumann; DD-Z: n=12; ID-Z: n=12) from the same datasets. The marginal fit of the resulting frameworks and the accuracy of the underlying datasets from DD and ID were evaluated. Data were analyzed by unpaired two sample Student's t-test with Levene-test (p<0.05).

RESULTS: Frameworks from group DD-C showed significantly better marginal fit than ID-C (DD-C: 56.90±27.37 μm, ID-C: 90.64±90.81 μm). For zirconia frameworks no differences between both digitalization methods (DD-Z: 127.23±66.87 μm, ID-Z: 141.08±193.17 μm) could be observed. Base metal alloy frameworks exhibited significantly better marginal fit than zirconia frameworks (DD: p<0.001; ID: p=0.022). Regarding the accuracy group DD showed significantly higher "trueness" than ID.

SIGNIFICANCE: Direct and indirect digitalization lead to clinically acceptable marginal fit of 4-unit FDPs from base metal alloy and zirconia. Higher accuracy of datasets from DD leads to better marginal fit of frameworks from base metal alloy but not for ones from zirconia.}, } @article {pmid24521894, year = {2013}, author = {Li, B and Hua, B and Lu, X and Chen, Y and Xiao, WZ}, title = {[Treatment options for elderly breast cancer patients over 70 years old].}, journal = {Zhonghua yi xue za zhi}, volume = {93}, number = {44}, pages = {3523-3525}, pmid = {24521894}, issn = {0376-2491}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Female ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: To analyze the clinical characteristics and therapeutics of elderly patients with breast carcinomas.

METHODS: A total of 312 patients (≥ 70 years old) admitted into Breast Center of Beijing Hospital from September 1997 to September 2011 were included for this retrospective study. Their clinical characteristics, treatment options and prognostic factors were analyzed.

RESULTS: They accounted for 14.6% (312/2137) of breast cancer patients treated during the same period. The predominant complaint was palpable mass (n = 250, 80.1%). 90.4% (n = 282) of them were complicated with other diseases. The major pathologic type was invasive ductal carcinoma of non-special type (n = 248, 79.5%). The positive rate of estrogen receptor (ER) and(or) progesterone receptor (PR) was 75.3% (n = 235), and 15.7% (n = 49) cases were Cerb-B2 (+ + +) . The 5, 10-year overall survival were 75.0% and 41.8% respectively. TNM stage, vascular thrombosis, operative regimen and adjuvant therapy were prognostic factors.

CONCLUSIONS: Surgical operation and endocrine therapy are the first choice remedies for elderly patients. And the major prognostic factors are TNM stage, vascular thrombosis and treatment regimens.}, } @article {pmid24512624, year = {2014}, author = {Babina, IS and McSherry, EA and Donatello, S and Hill, AD and Hopkins, AM}, title = {A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.}, journal = {Breast cancer research : BCR}, volume = {16}, number = {1}, pages = {R19}, pmid = {24512624}, issn = {1465-542X}, mesh = {Breast/cytology/physiology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Cytoskeletal Proteins/metabolism ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Hyaluronan Receptors/genetics/*metabolism ; *Lipoylation ; Membrane Microdomains/*metabolism ; Mutagenesis, Site-Directed ; Neoplasm Invasiveness/*pathology ; Protein Binding ; Protein Processing, Post-Translational ; }, abstract = {INTRODUCTION: Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration.

METHODS: Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients.

RESULTS: CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures.

CONCLUSION: Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.}, } @article {pmid24512329, year = {2014}, author = {Kulzer, L and Rubner, Y and Deloch, L and Allgäuer, A and Frey, B and Fietkau, R and Dörrie, J and Schaft, N and Gaipl, US}, title = {Norm- and hypo-fractionated radiotherapy is capable of activating human dendritic cells.}, journal = {Journal of immunotoxicology}, volume = {11}, number = {4}, pages = {328-336}, doi = {10.3109/1547691X.2014.880533}, pmid = {24512329}, issn = {1547-6901}, mesh = {Antigens, CD/metabolism ; Antineoplastic Protocols ; CD4-Positive T-Lymphocytes/*immunology ; Cell Death ; Cell Differentiation ; Cell Line, Tumor ; Colorectal Neoplasms/immunology/*radiotherapy ; Cytokines/metabolism ; Dendritic Cells/*immunology/*radiation effects ; *Dose Fractionation, Radiation ; Humans ; Lymphocyte Activation ; Paracrine Communication ; }, abstract = {Despite the transient immunosuppressive properties of local radiotherapy (RT), this classical treatment modality of solid tumors is capable of inducing immunostimulatory forms of tumor-cell death. The resulting 'immunotoxicity' in the tumor, but not in healthy tissues, may finally lead to immune-mediated destruction of the tumor. However, little is known about the best irradiation scheme in this setting. This study examines the immunological effects of differently irradiated human colorectal tumor cells on human monocyte-derived dendritic cells (DC). Human SW480 tumor cells were irradiated with a norm-fractionation scheme (5 × 2 Gy), a hypo-fractionated protocol (3 × 5 Gy), and with a high single irradiation dose (radiosurgery; 1 × 15 Gy). Subsequently, human immature DC (iDC) were co-incubated with supernatants (SN) of these differently treated tumor cells. Afterwards, DC were analyzed regarding the expression of maturation markers, the release of cytokines, and the potential to stimulate CD4(+) T-cells. The co-incubation of iDC with SN of tumor cells exposed to norm- or hypo-fractionated RT resulted in a significantly increased secretion of the immune activating cytokines IL-12p70, IL-8, IL-6, and TNFα, compared to iDC co-incubated with SN of tumor cells that received a high single irradiation dose or were not irradiated. In addition, DC-maturation markers CD80, CD83, and CD25 were also exclusively elevated after co-incubation with the SN of fractionated irradiated tumor cells. Furthermore, the SN of tumor cells that were irradiated with norm- or hypo-fractionated RT triggered iDC to stimulate CD4(+) T-cells not only in an allogenic, but also in an antigen-specific manner like mature DC. Collectively, these results demonstrate that norm- and hypo-fractionated RT induces a fast human colorectal tumor-cell death with immunogenic potential that can trigger DC maturation and activation in vitro. Such findings may contribute to the improvement of irradiation protocols for the most beneficial induction of anti-tumor immunity.}, } @article {pmid24511745, year = {2013}, author = {Talghini, S}, title = {Is macromastia a risk factor for breast cancer? A study on 198 patients.}, journal = {Pakistan journal of biological sciences : PJBS}, volume = {16}, number = {21}, pages = {1348-1352}, doi = {10.3923/pjbs.2013.1348.1352}, pmid = {24511745}, issn = {1028-8880}, mesh = {Adult ; Breast/*abnormalities/pathology ; Breast Neoplasms/*pathology/surgery ; Cross-Sectional Studies/methods ; Female ; Humans ; Hypertrophy/*pathology ; Mammaplasty/methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; }, abstract = {Macromastia, or breast hypertrophy, is a very common finding and a frequent cause of reduction mammaplasty all over the world. This study aims to examine the breast tissue specimens obtained by reduction mammaplasty in patients with macromastia in terms of the frequency of histopathological abnormalities (malignant and non-malignant lesions). In this cross-sectional, retrospective study, paraffin-embedded specimens of breast tissue after reduction mammaplasty were histopathologically reviewed in Tabriz Imam Reza Teaching Hospital in three years (2010-2013). All the specimens were sectioned, stained and examined by an adroit pathologist. One hundred ninety eight out of 271 primary specimens were eligible for this study. The mean age of the patients was 37.09 +/- 8.98 (range: 20-59) years, with mean body mass index of 27.44 +/- 3.85 (range: 21-35) kg m(-2). Based on the findings of microscopic examination, normal tissue was present in 98 cases (49.5%), all with increased content of fat. Fibrocystic change was the prominent benign entity, which was reported in 47.5% of the cases. Intraductal papilloma was detected 2 cases (1%). There were 4 cases with malignant lesions (2%), including 2 cases (1%) with invasive ductal carcinoma (age: 22 and 31 years old) and 2 cases (1%) with lobular carcinoma in situ (age: 21 and 35 years old). Considering the intraductal papilloma as a premalignant condition, the total rate of non-benign lesions reached to 3%. Based on the results of the present study, macromastia may be considered as a risk factor of breast malignancy. Thorough histopathological examination of the breast specimens after reduction mammaplasty, as well as strict screening of the women with nonsurgical macromastia is highly recommended.}, } @article {pmid24508527, year = {2014}, author = {Goodyear, AW and Kumar, A and Dow, S and Ryan, EP}, title = {Optimization of murine small intestine leukocyte isolation for global immune phenotype analysis.}, journal = {Journal of immunological methods}, volume = {405}, number = {}, pages = {97-108}, doi = {10.1016/j.jim.2014.01.014}, pmid = {24508527}, issn = {1872-7905}, mesh = {Animals ; Antigens, CD/immunology/metabolism ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Separation/methods ; Cell Survival/immunology ; Dendritic Cells/cytology/immunology/metabolism ; Epithelial Cells/cytology/immunology/metabolism ; Female ; Immunophenotyping/methods ; Intestinal Mucosa/cytology/*immunology/metabolism ; Intestine, Small/cytology/*immunology/metabolism ; Killer Cells, Natural/cytology/immunology/metabolism ; Leukocytes/cytology/*immunology/metabolism ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Monocytes/cytology/immunology/metabolism ; Reproducibility of Results ; }, abstract = {New efforts to understand complex interactions between diet, gut microbiota, and intestinal immunity emphasize the need for a standardized murine protocol that has been optimized for the isolation of lamina propria immune cells. In this study multiple mouse strains including BALB/c, 129S6/Sv/EvTac and ICR mice were utilized to develop an optimal protocol for global analysis of lamina propria leukocytes. Incubation temperature was found to significantly improve epithelial cell removal, while changes in media formulation had minor effects. Tissue weight was an effective method for normalization of solution volumes and incubation times. Collagenase digestion in combination with thermolysin was identified as the optimal method for release of leukocytes from tissues and global immunophenotyping, based on the criteria of minimizing marker cleavage, improving cell viability, and reagent cost. The effects of collagenase in combination with dispase or thermolysin on individual cell surface markers revealed diverse marker specific effects. Aggressive formulations cleaved CD8α, CD138, and B220 from the cell surface, and resulted in relatively higher expression levels of CD3, γδ TCR, CD5, DX5, Ly6C, CD11b, CD11c, MHC-II and CD45. Improved collagenase digestion significantly improved viability and reduced debris formation, eliminating the need for density gradient purification. Finally, we demonstrate that two different digestion protocols yield significant differences in detection of CD4(+) and CD8(+) T cells, NK cells, monocytes and interdigitating DC (iDC) populations, highlighting the importance and impact of cell collection protocols on assay outputs. The optimized protocol described herein will help assure the reproducibility and robustness of global assessment of lamina propria immune responses. Moreover, this technique may be applied to isolation of leukocytes from the entire gastrointestinal tract.}, } @article {pmid24506966, year = {2013}, author = {Nie, D and You, QS and Luan, JW and Li, Y and Li, XL and Guo, RT and Zhang, LP and Wu, J}, title = {[Long-term results of personalized treatment in 72 breast cancer patients who failed chemotherapy].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {35}, number = {12}, pages = {941-945}, pmid = {24506966}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aromatase Inhibitors/therapeutic use ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Brain Neoplasms/drug therapy/secondary ; Breast Neoplasms/*drug therapy/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/radiotherapy/secondary/surgery ; Chemotherapy, Adjuvant ; Diphosphonates/therapeutic use ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Imidazoles/therapeutic use ; Letrozole ; Lung Neoplasms/drug therapy/secondary ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm Staging ; Nitriles/therapeutic use ; Radiotherapy, Adjuvant ; Radiotherapy, Conformal/*methods ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Triazoles/therapeutic use ; Zoledronic Acid ; }, abstract = {OBJECTIVE: To evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy.

METHODS: Seventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients.

RESULTS: The median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed.

CONCLUSION: Chinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.}, } @article {pmid24506959, year = {2013}, author = {Zhang, B and Liu, FF and Ma, YJ and Gu, F}, title = {[Cytoplasmic expression of aquaporin-1 in breast cancer cells and its relationship with clinicopathological characteristics and prognosis].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {35}, number = {12}, pages = {904-909}, pmid = {24506959}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aquaporin 1/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cytoplasm/*metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/metabolism/pathology ; Lymphatic Metastasis ; Mammary Glands, Human/metabolism/pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {OBJECTIVE: To detect the expression of aquaporin 1 (AQP1) in breast cancer tissues, and to analyze its relationship with clinicopathological characteristics and prognosis of breast cancer patients.

METHODS: Histochemical SP staining was used to assess the AQP1 expression in 30 cases of lobular hyperplasia of mammary gland, 16 cases of ductal carcinoma in situ (DCIS), and 78 cases of invasive ductal carcinoma-not otherwise specified (IDC-NOS), and to analyze the relationship between cytoplasmic expression of AQP1 in IDC-NOS and clinical pathological characteristics and prognosis of the patients.

RESULTS: Positive AQP1 immunolabelling appeared as brown deposit over the membrane of myoepithelial cells in all cases of lobular hyperplasia of mammary gland, but only 10.0% of cases showed cytoplasmic staining in glandular epithelial cells. In the ductal carcinoma in situ, brown deposit of AQP1 immunolabelling appeared over the myoepithelial cell membrane in all cases, but only 12.5% of cases were accompanied with cytoplasmic staining in glandular epithelial cells. In the invasive ductal carcinoma not otherwise specified, 35.9% of the cases showed cytoplasmic AQP1 immunoreactivity, but only 3.8% of cases showed positive membrane staining of the tumor cells. There were highly positive AQP1 expression in 14 cases, weakly positive in 14 cases, and negative in 50 cases. Cytoplasmic AQP1 expression in the IDC-NOS cases was significantly correlated with pathologic stage, PR, HER-2, lymph node status, Nottingham prognostic index (NPI) and metastasis or recurrence (all P < 0.05). The 5-year progression-free survival (PFS) rates were 16.8% in the patients with strong positive AQP1 expression, 90.9% in the cases with weakly positive AQP1 expression and 94.9% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors for PFS (both P < 0.05). The 5-year overall survival (OS) rates were 45.6% in the AQP1- strong positive cases, 90.0% in the AQP1-weakly positive cases and 97.7% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors affecting the overall survival and progression-free survival (both P < 0.05).

CONCLUSION: AQP1 is mainly expressed on the membrane of myoepithelial cells in the benign breast lesions, but in the cytoplasm of breast cancer cells, and its expression is an independent factor affecting prognosis of breast cancer patients.}, } @article {pmid24505951, year = {2013}, author = {Sas-Korczyńska, B and Mituś, J and Stelmach, A and Ryś, J and Martynów, D}, title = {[Apocrine breast cancer in the material from Cancer Centre in Krakow. Clinical features and treatment results in patients treated between 1952 and 2002].}, journal = {Ginekologia polska}, volume = {84}, number = {12}, pages = {1036-1040}, doi = {10.17772/gp/1676}, pmid = {24505951}, issn = {0017-0011}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/mortality/pathology/*therapy ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Poland/epidemiology ; Prognosis ; Survival Rate ; Treatment Outcome ; }, abstract = {UNLABELLED: Apocrine breast cancer is a rare type of neoplasm and accounts for approximately 0.3-4% of all breast cancers. It most frequently diagnosed in women over the age of 50.

OBJECTIVES: The purpose of the study was to present the clinical characteristics and treatment outcomes of 53 patients treated from apocrine breast cancer at the Oncology Center in Kraków between 1955 and 2002..

MATERIAL AND METHODS: Stage I or II carcinomas were found in 37 patients (69.8%) of the study group and 16 patients (30.2%) were classified as stage II. Node metastases were observed in 27 patients (50.9%). Surgery constituted the primary method of treatment and was used in all patients. Forty-nine patients underwent mastectomy and 4 underwent breast conserving surgery Post-operative radiotherapy was given to 16 patients. Chemotherapy and hormonal therapy were also used--in 20 and 26 cases, respectively.

RESULTS: The follow-up period in the study group was maximum 207 months. The 10-year survival rates were as follows: 75.9% (overall survival) and 58.1% (disease-free survival). It was shown that positive lymph nodes highly affected symptoms-free free survival. During follow-up, 7 patients developed local recurrence, 16 patients developed distant metastases. Second primary malignancies were found in 5 patients.

CONCLUSIONS: Our findings confirm good prognosis in patients treated for apocrine breast cancer similar to invasive ductal carcinoma.}, } @article {pmid24505513, year = {2013}, author = {Mousavi, SA and Mashhadi, E and Iravani, M and Ghavamzade, A}, title = {The Assessment of Response to Adjuvant Chemotherapy with CMF in Triple Negative Breast Cancer.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {7}, number = {1}, pages = {5-8}, pmid = {24505513}, issn = {2008-3009}, abstract = {INTRODUCTION: Breast cancers are divided into at least 4 sub Types on the Basis of gene expression profiles and expression of receptors as measured by IHC (Immunohistochemical). Triple negative breast cancer (TNBC) is more chemosensitive yet. It is much harder to detect than other sub types. At present lack of highly effective therapeutic targets for TNBC, standard chemotherapy is the only medical treatment but it is not remarkably efficient. CMF (cyclophosphamide-MTX-5-fu) chemotherapy is effective in some sub types of TNBC.

PATIENTS AND METHODS: A Total of 40 patients with TNBC who had undergone surgical resection because of primary Invasive Breast cancer were studied from 2009 to 2011. Twenty patients in treatment group received four cycles of modified CMF after standard chemotherapy and 20 patients in group control received standard chemotherapy (antracycline/taxane), patients were regularly followed up every 3 months for median observation 13.3 months.

RESULTS: In our study the prevalence of TNBC was %13.5. The average age of patients was 49.5 years. Their clinical and histopathological characteristics include: 90% Invasive Ductal carcinoma, 55.35% LN(Lymph node) pos, 61.3% P53 Pos, 74.5% Ki67 ≥ 20, 68% grade III. There was No statistical differenced between control and treatment group in OS and DFS Followed up 13.3 months.

CONCLUSION: The results of study indicate that the adjuvant therapy with regimen CMF in TNBC patient after standard chemotherapy with antracyline / taxane- Base no affected out come in patient in Median follow up 13.3 months.}, } @article {pmid24502182, year = {2013}, author = {Fernández, A and Reigosa, A}, title = {[Molecular classification of breast cancer patients obtained through the technique of chromogenic in situ hybridization (CISH)].}, journal = {Investigacion clinica}, volume = {54}, number = {4}, pages = {406-416}, pmid = {24502182}, issn = {0535-5133}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*classification/*genetics ; Cross-Sectional Studies ; Female ; Humans ; In Situ Hybridization/*methods ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {Breast cancer is a heterogeneous disease composed of a growing number of biological subtypes, with substantial variability of the disease progression within each category. The aim of this research was to classify the samples object of study according to the molecular classes of breast cancer: luminal A, luminal B, HER2 and triple negative, as a result of the state of HER2 amplification obtained by the technique of chromogenic in situ hybridization (CISH). The sample consisted of 200 biopsies fixed in 10% formalin, processed by standard techniques up to paraffin embedding, corresponding to patients diagnosed with invasive ductal carcinoma of the breast. These biopsies were obtained from patients from private practice and the Institute of Oncology "Dr. Miguel Pérez Carreño", for immunohistochemistry (IHC) of hormone receptors and HER2 made in the Hospital Metropolitano del Norte, Valencia, Venezuela. The molecular classification of the patient's tumors considering the expression of estrogen and progesterone receptors by IHC and HER2 amplification by CISH, allowed those cases originally classified as unknown, since they had an indeterminate (2+) outcome for HER2 expression by IHC, to be grouped into the different molecular classes. Also, this classification permitted that some cases, initially considered as belonging to a molecular class, were assigned to another class, after the revaluation of the HER2 status by CISH.}, } @article {pmid24497787, year = {2014}, author = {Yi, J and Lee, EH and Kwak, JJ and Cha, JG and Jung, SH}, title = {Retrieval rate and accuracy of ultrasound-guided 14-G semi-automated core needle biopsy of breast microcalcifications.}, journal = {Korean journal of radiology}, volume = {15}, number = {1}, pages = {12-19}, pmid = {24497787}, issn = {2005-8330}, mesh = {Adult ; Aged ; Biopsy, Large-Core Needle/*methods/standards ; Breast/*pathology ; Breast Diseases/diagnostic imaging/pathology ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Calcinosis/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology ; Female ; Humans ; Middle Aged ; Radiography ; *Ultrasonography, Interventional/standards ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the retrieval rate and accuracy of ultrasound (US)-guided 14-G semi-automated core needle biopsy (CNB) for microcalcifications in the breast.

MATERIALS AND METHODS: US-guided 14-G semi-automated CNB procedures and specimen radiography were performed for 33 cases of suspicious microcalcifications apparent on sonography. The accuracy of 14-G semi-automated CNB and radiology-pathology concordance were analyzed and the microcalcification characteristics between groups with successful and failed retrieval were compared.

RESULTS: Thirty lesions were successfully retrieved and the microcalcification retrieval rate was 90.9% (30/33). Thirty lesions were successfully retrieved. Twenty five were finally diagnosed as malignant (10 invasive ductal carcinoma, 15 ductal carcinoma in situ [DCIS]) and five as benign. After surgery and mammographic follow-up, the 25 malignant lesions comprised 12 invasive ductal carcinoma and 13 DCIS. Three lesions in the failed retrieval group (one DCIS and two benign) were finally diagnosed as two DCIS and one benign after surgery. The accuracy of 14-G semi-automated CNB was 90.9% (30/33) because of two DCIS underestimates and one false-negative diagnosis. The discordance rate was significantly higher in the failed retrieval group than in the successful retrieval group (66.7% vs. 6.7%; p < 0.05). Punctate calcifications were significantly more common in the failed retrieval group than in the successful retrieval group (66.7% vs. 3.7%; p < 0.05).

CONCLUSION: US-guided 14-G semi-automated CNB could be a useful procedure for suspicious microcalcifications in the breast those are apparent on sonography.}, } @article {pmid24497139, year = {2013}, author = {Kobierzycki, C and Wojnar, A and Dziegiel, P}, title = {Expression of SATB1 protein in the ductal breast carcinoma tissue microarrays - preliminary study.}, journal = {Folia histochemica et cytobiologica}, volume = {51}, number = {4}, pages = {333-338}, doi = {10.5603/FHC.2013.0045}, pmid = {24497139}, issn = {1897-5631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Female ; Humans ; Ki-67 Antigen/genetics/metabolism ; Matrix Attachment Region Binding Proteins/genetics/*metabolism ; Middle Aged ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Tissue Array Analysis ; }, abstract = {Special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein which interacts with specific regions of DNA, ensuring its proper organization and function in the cell. The expression of SATB1 was primarily found in thymocytes, but its increased levels were observed in various types of cancers. However, the knowledge of the function and application possibilities of this protein is still limited. The aim of this study was to investigate the expression of SATB1 protein using immunohistochemistry and tissue microarray (TMA) technique and determine its possible relationship with the proliferative marker Ki-67, estrogen a (ER) and progesterone (PR) receptors as well as grade of histological malignancy (G). The study was performed on material of 48 archival invasive ductal breast cancers (IDC). The TMAs were prepared with the use of 0.6 mm diameter punches. Immunohistochemical reactions were carried out using antibodies against Ki-67, ER, PR and SATB1 proteins. The intensity of the nuclear reaction was evaluated using a light microscope and computer-assisted image analysis. Expression of Ki-67 and SATB1 protein was observed in 89.58% and 31.25% of cancer cases, respectively. 62.5% of tumors were classified as ER-positive, and 47.92% as PR-positive. Statistical analysis showed a moderate positive correlation between Ki-67 and SATB1 expression (r = 0.291, p = 0.045 independently on the receptor status, and r = 0.392, p = 0.032 in ER-negative tumors). The expression of the Ki-67 antigen increased with higher grade of histological malignancy (G). The results suggest that SATB1 protein may play an indirect role in the cell proliferation and should be evaluated in relation to the other markers. Further studies concerning determination of its role in cancer progression and metastasis, in terms of application as therapeutic target and prognostic marker, are recommended.}, } @article {pmid24496929, year = {2014}, author = {Ito, M and Hagiyama, M and Mimae, T and Inoue, T and Kato, T and Yoneshige, A and Nakanishi, J and Kondo, T and Okada, M and Ito, A}, title = {α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {144}, number = {1}, pages = {59-69}, doi = {10.1007/s10549-014-2859-0}, pmid = {24496929}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Blotting, Western ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Lobular/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Mass Spectrometry ; Microfilament Proteins/*metabolism ; Middle Aged ; Proteomics ; Pseudopodia/metabolism ; }, abstract = {Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, α-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with α-parvin expression. Twenty-one (37.5 %) ILCs stained positive for α-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). α-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. α-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that α-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.}, } @article {pmid24489812, year = {2014}, author = {Liu, T and Zhang, XY and He, XH and Geng, JS and Liu, Y and Kong, DJ and Shi, QY and Liu, F and Wei, W and Pang, D}, title = {High levels of BCOX1 expression are associated with poor prognosis in patients with invasive ductal carcinomas of the breast.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86952}, pmid = {24489812}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Demography ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics/metabolism ; Prognosis ; Proportional Hazards Models ; RNA, Messenger/genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; }, abstract = {This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast.}, } @article {pmid24489766, year = {2014}, author = {Jiang, YZ and Xia, C and Peng, WT and Yu, KD and Zhuang, ZG and Shao, ZM}, title = {Preoperative measurement of breast cancer overestimates tumor size compared to pathological measurement.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86676}, pmid = {24489766}, issn = {1932-6203}, mesh = {Adult ; Breast/*pathology ; Carcinoma, Ductal, Breast/diagnosis/diagnostic imaging/mortality/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Neoplasm Grading ; Preoperative Period ; Retrospective Studies ; Survival Analysis ; Tumor Burden ; }, abstract = {BACKGROUND: Tumor size is one of the most important factors in making clinical and pathological assessment of breast cancer. In the present study, we aimed to determine whether the preoperative measurement of tumor size, by imaging modalities, deviate from the postoperative pathological measurement in breast cancer.

PATIENTS AND METHODS: 1296 patients diagnosed with invasive ductal breast carcinoma (IDC) during 2007 and 2009 were involved. Pre- and postoperative measurements of tumor size were compared using paired t-test and Chi-square test.

RESULTS: The mean maximum diameters of tumors by imaging modalities and pathology were 27.9 mm and 22.4 mm, respectively. There was a statistically significant difference of 5.5 mm (95% CI: 4.7-6.2, p<0.001) between them. The discordance between pre- and post-surgical measurements of tumor size had significant effect on choosing surgery type, causing less application of breast conserving therapy (p<0.0001).

CONCLUSION: Compared to pathological size, preoperative measurement by imaging modalities tends to overestimate tumor size. These differences could have implications in the treatment of patients with breast cancer.}, } @article {pmid24481994, year = {2014}, author = {Lee, SK and Kim, SW and Han, SA and Kil, WH and Lee, JE and Nam, SJ}, title = {The protective effect of parity in hormone receptor-positive, Ki-67 expressing breast cancer.}, journal = {World journal of surgery}, volume = {38}, number = {5}, pages = {1065-1069}, pmid = {24481994}, issn = {1432-2323}, mesh = {Adult ; Breast Neoplasms/*epidemiology/*metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/*biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; *Parity ; Protective Factors ; Receptor, ErbB-2/*biosynthesis ; Retrospective Studies ; }, abstract = {BACKGROUND: Epidemiologic studies showed that the experience of pregnancy is associated with a reduced risk of breast cancer. We hypothesized that parity may differentially be associated with the development of invasive breast cancer by each subtype.

METHODS: We reviewed the clinical, radiological, and pathological records of women diagnosed with invasive ductal carcinoma of the breast at Samsung Medical Center between 2005 and 2009. Clinicopathologic results were assessed by χ(2) and Fisher's exact tests with a Bonferroni correction for categorical variables, and by the Kruskal-Wallis test for nonparametric continuous variables. A multinomial logistic regression model was used for multivariate analysis.

RESULTS: Among a total of 3,095 patients, 283 (9.14 %) patients were nulliparous. Older age, higher pN, and expression of HER2 were associated with parity. In the analysis between parity and molecular subtypes, parity also had a variable influence on breast cancer subtypes (p = 0.032). Intergroup analysis with multiple comparison showed that luminal B subtype was related to nulliparity compared with HER2-positive subtypes (p = 0.03).

CONCLUSIONS: The effect of parity on the development of breast cancer differed by hormone receptor and HER2 expression. It seems that parity might have a protective effect against hormone receptor-positive breast cancer, especially cancers expressing HR+ and Ki-67. Further basic research to define and understand this result is ongoing.}, } @article {pmid24481730, year = {2014}, author = {Kimura, K and Tsuzuki, T and Kato, M and Saito, AM and Sassa, N and Ishida, R and Hirabayashi, H and Yoshino, Y and Hattori, R and Gotoh, M}, title = {Prognostic value of intraductal carcinoma of the prostate in radical prostatectomy specimens.}, journal = {The Prostate}, volume = {74}, number = {6}, pages = {680-687}, doi = {10.1002/pros.22786}, pmid = {24481730}, issn = {1097-0045}, mesh = {Adenocarcinoma/blood/*pathology/surgery ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prognosis ; Prostate/*pathology/surgery ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/blood/*pathology/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an adverse prognostic factor for radical prostatectomy (RP). The endpoint in most IDC-P studies is increased prostate-specific antigen (PSA) levels. The aim of this study was to evaluate whether IDC-P in RP specimens is an adverse prognostic factor for progression-free survival (PFS) and cancer-specific survival (CSS).

METHODS: We retrospectively evaluated 206 high-risk prostate cancer patients treated with RP and analyzed data on age, serum PSA level at diagnosis, biopsy Gleason score (bGS), surgical margin (SM), clinical T stage (cT), extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LN), and neoadjuvant therapy.

RESULTS: An IDC-P component was found in 104 cases. Forty-four patients experienced clinical failure, and 20 patients died of the disease. Patients with IDC-P showed a higher bGS and stage (including cT, EPE, SVI, and LN) than those without IDC-P. In univariate analysis, IDC-P, PSA level, bGS, SM, cT, SVI, LN, and EPE (P < 0.0001) were significantly associated with PFS. IDC-P (P = 0.0004), PSA level (P < 0.0001), SM (P = 0.0013), cT (P = 0.0019), SVI (P = 0.0012), and LN (P = 0.0002) were significantly associated with CSS. In multivariate analysis, IDC-P (P = 0.0038), and cT (P = 0.0001) were significantly associated with PFS. IDC-P (P = 0.0238) and PSA level (P = 0.0112) were significantly associated with CSS.

CONCLUSIONS: IDC-P in RP specimens was an independent risk factor for PFS and CSS and could predict clinical outcomes.}, } @article {pmid24479854, year = {2014}, author = {Kővári, B and Rusz, O and Schally, AV and Kahán, Z and Cserni, G}, title = {Differential immunostaining of various types of breast carcinomas for growth hormone-releasing hormone receptor - Apocrine epithelium and carcinomas emerging as uniformly positive.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {9}, pages = {824-831}, doi = {10.1111/apm.12224}, pmid = {24479854}, issn = {1600-0463}, mesh = {Breast Neoplasms/classification/diagnosis/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Mammary Glands, Human/*metabolism ; Mammography ; RNA, Messenger/biosynthesis ; Receptor, ErbB-2/metabolism ; Receptors, Neuropeptide/biosynthesis/genetics/*metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/biosynthesis/genetics/*metabolism ; Retrospective Studies ; }, abstract = {Different classes of breast cancers were explored for their positivity for growth hormone-releasing hormone receptors (GHRH-R) in this pilot study, as no systematic evaluation of such tumors has been performed to date. Seventy-two small primary breast carcinomas were evaluated for GHRH-R expression by immunohistochemistry using a polyclonal antibody and a cutoff value of 10% staining. GHRH-R positivity was detected in 58% of all cases, 20/23 (87%) of invasive lobular carcinomas (ILC) and 22/46 (48%) of invasive ductal carcinomas (IDC). GHRH-R positivity was more frequent in grade 2 tumors (86%), as compared to grade 1 (18%) or grade 3 (47%) cancers. GHRH-R expression was not associated with mitotic scores, the Ki-67 labeling indices or nodal status. IDCs with casting-type calcifications on the mammogram showed positivity for GHRH-R in 9/12 (75%) cases. Most importantly, apocrine epithelium, and all 10 apocrine carcinomas added later to the study were GHRH-R-positive. These preliminary results suggest a greater than average GHRH-R expression in ILCs and IDCs associated with casting-type calcifications on the mammogram. Apocrine carcinomas seem uniformly positive for GHRH-R. Whether these findings could indicate a potential role of GHRH-antagonists in targeted treatment of these types of breast cancer requires further studies.}, } @article {pmid24477715, year = {2014}, author = {O'Donnell, E and Havyer, R}, title = {Breast malignancy masquerading under the cloak of acute urticaria.}, journal = {BMJ case reports}, volume = {2014}, number = {}, pages = {}, pmid = {24477715}, issn = {1757-790X}, mesh = {Breast Neoplasms/*complications/diagnosis/surgery ; Carcinoma, Ductal, Breast/*complications/diagnosis/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Urticaria/*etiology ; }, abstract = {Urticaria is a common disorder characterised by well-demarcated and intensely pruritic erythematous skin swellings. Common triggers include infection, allergic reactions or medications. While often idiopathic, the presence of urticaria can be associated with underlying systemic disease. We report a case of a patient who presented with diffuse and refractory urticaria. A thorough workup was conducted to determine the aetiology including routine age-appropriate cancer screening. Mammography revealed four lesions in the patient's left breast with biopsy consistent with invasive ductal carcinoma. Disappearance of the urticarial lesions with mastectomy suggests an association between breast malignancy and urticaria. Thus, refractory urticaria with unknown cause should prompt a thorough history, physical examination and review of age-appropriate cancer screening.}, } @article {pmid24475830, year = {2014}, author = {Ko, ES and Han, BK and Kim, RB and Cho, EY and Ahn, S and Nam, SJ and Ko, EY and Shin, JH and Hahn, SY}, title = {Apparent diffusion coefficient in estrogen receptor-positive invasive ductal breast carcinoma: correlations with tumor-stroma ratio.}, journal = {Radiology}, volume = {271}, number = {1}, pages = {30-37}, doi = {10.1148/radiol.13131073}, pmid = {24475830}, issn = {1527-1315}, mesh = {Aged ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Somatotropin/metabolism ; Retrospective Studies ; Tumor Microenvironment ; }, abstract = {PURPOSE: To determine whether apparent diffusion coefficient (ADC) values vary according to tumor-stroma ratio, dominant stroma type, or presence of central fibrosis in estrogen receptor-positive breast cancer.

MATERIALS AND METHODS: Institutional review board approval was obtained, and patient consent was waived. Sixty-one patients with estrogen receptor-positive invasive ductal carcinoma-not otherwise specified who underwent breast magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging were included in this study. The ADC values of the lesions were measured. Two pathologists evaluated the tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and central fibrosis. Detectability on DW images was compared between the two groups according to the tumor-stroma ratio (stroma rich or stroma poor). Mean ADC values were retrospectively compared with the tumor-stroma ratio, dominant stroma type, and presence of a central fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with ADC.

RESULTS: On DW images, detectability was not significantly different between stroma-rich and stroma-poor groups (P = .244). ADC values were significantly lower in the stroma-poor group (P < .001). The mean ADC values in the collagen-dominant type were lower than in fibroblast-dominant or lymphocyte-dominant types (P = .021). In multiple linear regression analysis, tumor-stroma ratio (P = .007), tumor size (P = .007), and dominant stroma type (collagen dominant, P = .029) were independently correlated with ADC.

CONCLUSION: In estrogen receptor-positive breast cancers, ADC values showed significant differences according to the tumor-stroma ratio and dominant stroma type.}, } @article {pmid24475103, year = {2014}, author = {Yang, AX and Chong, N and Jiang, Y and Catalano, J and Puri, RK and Khleif, SN}, title = {Molecular characterization of antigen-peptide pulsed dendritic cells: immature dendritic cells develop a distinct molecular profile when pulsed with antigen peptide.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e86306}, pmid = {24475103}, issn = {1932-6203}, mesh = {Antigen Presentation/*genetics ; Dendritic Cells/*cytology/*metabolism ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation/*immunology ; HLA-A2 Antigen/metabolism ; Humans ; Image Processing, Computer-Assisted ; Immunotherapy/*methods ; Microarray Analysis ; Papillomavirus E7 Proteins/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {As dendritic cells (DCs) are the most potent professional antigen-presenting cells, they are being tested as cancer vaccines for immunotherapy of established cancers. Although numerous studies have characterized DCs by their phenotype and function, few have identified potential molecular markers of antigen presentation prior to vaccination of host. In this study we generated pre-immature DC (piDC), immature DC (iDC), and mature DC (mDC) from human peripheral blood monocytes (PBMC) obtained from HLA-A2 healthy donors, and pulsed them with human papillomavirus E7 peptide (p11-20), a class I HLA-A2 binding antigen. We then characterized DCs for cell surface phenotype and gene expression profile by microarray technology. We identified a set of 59 genes that distinguished three differentiation stages of DCs (piDC, iDC and mDC). When piDC, iDC and mDC were pulsed with E7 peptide for 2 hrs, the surface phenotype did not change, however, iDCs rather than mDCs showed transcriptional response by up-regulation of a set of genes. A total of 52 genes were modulated in iDC upon antigen pulsing. Elongation of pulse time for iDCs to 10 and 24 hrs did not significantly bring further changes in gene expression. The E7 peptide up-modulated immune response (KPNA7, IGSF6, NCR3, TREM2, TUBAL3, IL8, NFKBIA), pro-apoptosis (BTG1, SEMA6A, IGFBP3 and SRGN), anti-apoptosis (NFKBIA), DNA repair (MRPS11, RAD21, TXNRD1), and cell adhesion and cell migration genes (EPHA1, PGF, IL8 and CYR61) in iDCs. We confirmed our results by Q-PCR analysis. The E7 peptide but not control peptide (PADRE) induced up-regulation of NFKB1A gene only in HLA-A2 positive iDCs and not in HLA-A2 negative iDCs. These results suggest that E7 up-regulation of genes is specific and HLA restricted and that these genes may represent markers of antigen presentation and help rapidly assess the quality of dendritic cells prior to administration to the host.}, } @article {pmid24472480, year = {2013}, author = {Laird-Fick, HS and Gardiner, JC and Tokala, H and Patel, P and Wei, S and Dimitrov, NV}, title = {HER2 status in elderly women with breast cancer.}, journal = {Journal of geriatric oncology}, volume = {4}, number = {4}, pages = {362-367}, doi = {10.1016/j.jgo.2013.05.007}, pmid = {24472480}, issn = {1879-4076}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; Carcinoma, Ductal, Breast/chemistry ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; }, abstract = {OBJECTIVES: HER2 (human epidermal growth factor receptor 2) is an important biomarker in breast cancer, but its prevalence in elderly women is not well established. Previous studies reported HER2 status based on either immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) interchangeably. However, the tests may give discordant results. We report the prevalence of HER2 amplification in elderly women using only FISH.

MATERIALS AND METHODS: We retrospectively identified women 65 years and older undergoing core biopsy, lumpectomy or mastectomy for primary breast malignancy at a single institution between 2009 and 2011. Data collected included age, histopathological type, hormone receptor status, and HER2 status. Descriptive statistics were performed using SAS Software, Version 9.2.

RESULTS: One hundred fifty-eight women were included in the study. Most had invasive ductal carcinoma (74.7%), and were positive for either estrogen (ER) or progesterone (PgR) receptors (82.3% and 70.0%, respectively). Only 17% were negative for both ER and PgR; 11.4% were triple negative. Nineteen samples (12.0%) were positive for HER2. In univariate analyses, hormone receptor and HER2 status did not vary with age. When stratified by age, 60% of women with hormone receptor/HER2 positive tumors were younger than 70 years, compared with 22.2-33.3% of women in other subgroups. The difference was not statistically significant (p=0.20).

CONCLUSION: This study adds to the knowledge of the biology of breast cancer in elderly women. Triple negative tumor incidence was similar to that previously reported for women under 70 years old, but HER2 positive tumors were less common. Additional prospective studies are needed to confirm our findings.}, } @article {pmid24465383, year = {2014}, author = {Di Caro, V and Phillips, B and Engman, C and Harnaha, J and Trucco, M and Giannoukakis, N}, title = {Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e83575}, pmid = {24465383}, issn = {1932-6203}, support = {R21 DK063499/DK/NIDDK NIH HHS/United States ; R33 DK063499/DK/NIDDK NIH HHS/United States ; DK063499/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD19/metabolism ; B-Lymphocytes/cytology/drug effects/*immunology ; Cell Proliferation/drug effects ; Dendritic Cells/drug effects/*immunology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Female ; Flow Cytometry ; Humans ; Hyperglycemia/immunology ; *Immune Tolerance/drug effects ; Immunomodulation/drug effects ; Interleukin-10/metabolism ; Lymphocyte Activation/drug effects ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred NOD ; Mice, Transgenic ; Oligonucleotides, Antisense/pharmacology ; Receptors, Retinoic Acid/metabolism ; Spleen/cytology ; }, abstract = {The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.}, } @article {pmid24460307, year = {2013}, author = {Sedighi, A and Hamed, EA and Mohammadian, K and Behnood, S and Kalaghchi, B}, title = {Clinicopathologic characteristics of male breast cancer: a report of 21 cases in radiotherapy center of hamedan, iran.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {12}, pages = {7381-7383}, doi = {10.7314/apjcp.2013.14.12.7381}, pmid = {24460307}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology/therapy ; Carcinoma, Medullary/metabolism/*pathology/therapy ; Combined Modality Therapy ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Iran ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/metabolism/*pathology/therapy ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Male breast cancer accounts for less than 1% of all cancer in men and only around 1% of all diagnosed breast cancer. Despite a significant raise in the last 25 years, it still remains a rare disease.

MATERIALS AND METHODS: We conducted a retrospective study from 2004-2011 with 21 male breast cancer patients. We aimed to analyze the epidemiologic data (age, personal and family history), tumor characteristics (size, histological type, location, TNM stage, receptors), surgery, adjuvant chemotherapy and radiation therapy, hormonal therapy and survival (relapse, follow up, death) who reffered to our center with breast cancer.

RESULTS: The median age was 49.2±14.2 years (range 30-83 years). A family history of breast cancer was noted in four cases. The main clinical complaint was a retroareolar mass in 85.7%of patients (n=18). Histologically, 85.7% (n=18)were invasive ductal carcinoma and 4.7% (n=1) had ductal carcinoma in situ and 9.4% (n=2) had mixed histology including invasive medullary and ductal carcinoma. Hormonal therapy was delivered to 16 cases (76.1%) due to ER or PR positivity. During median follow up of 30 months (3-84 month), distant metastases were evident in 4 cases (19%). During the follow-up period, only one patient died due to metastatic disease. The mean time to recurrence detection was 30 months.

CONCLUSIONS: The percentage of cases of male breast cancer is very low compared to breast cancer in females, explaining why very few investigations have been conducted in Iran. Limited coverage in the literature make gender-specific findings difficult so future research of this entity involving multi-institutional cooperation and longer follow up is essential to provide new insights about the biological and clinical factors of this rare cancer.}, } @article {pmid24458308, year = {2014}, author = {Fu, J and Zhang, L and Song, S and Sheng, K and Li, Y and Li, P and Song, S and Wang, Q and Chu, J and Wei, W}, title = {Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {63}, number = {5}, pages = {357-367}, pmid = {24458308}, issn = {1420-908X}, mesh = {Animals ; Antigens, Differentiation/*analysis ; Arthritis, Experimental/*immunology/therapy ; Bone Marrow Cells/*physiology ; CD11b Antigen/*analysis ; Cell Proliferation ; Cells, Cultured ; Cytokines/*physiology ; Dendritic Cells/*physiology ; Interleukin-10/physiology ; Interleukin-17/physiology ; Male ; Mice ; Mice, Inbred DBA ; Thymocytes/physiology ; }, abstract = {OBJECTIVE: To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA).

METHODS: BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels.

RESULTS: BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice.

CONCLUSIONS: BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.}, } @article {pmid24454468, year = {2013}, author = {Sarma, M and Borde, C and Subramanyam, P and Shanmuga Sundaram, P}, title = {Random synchronous malignancy in male breast: a case report.}, journal = {Journal of breast cancer}, volume = {16}, number = {4}, pages = {442-446}, pmid = {24454468}, issn = {1738-6756}, abstract = {We report here a case of a random synchronous male breast malignancy in a patient with a known base of tongue malignancy that was incidentally detected on a whole body 18-fluorine deoxyglucose positron emission tomography and computed tomography ((18)F-FDG PET/CT). Patient was referred to us for PET/CT staging and radiotherapy planning for a poorly differentiated squamous cell carcinoma of base of tongue. Histopathologically, the incidentally detected breast lesion was proven to be an invasive ductal carcinoma. (18)F-FDG PET/CT being a whole body imaging modality is known to detect a considerable number of synchronous primaries. Synchronous malignancies in the head and neck area and the upper aerodigestive tract are well established. However, synchronous malignancy in male breast is reportedly uncommon. Our case is unique for the fact that a random synchronous dual malignancy of base of tongue and breast in a male patient was detected during a whole body (18)F-FDG PET/CT imaging.}, } @article {pmid24454464, year = {2013}, author = {Park, I and Kim, J and Kim, M and Bae, SY and Lee, SK and Kil, WH and Lee, JE and Nam, SJ}, title = {Comparison of the characteristics of medullary breast carcinoma and invasive ductal carcinoma.}, journal = {Journal of breast cancer}, volume = {16}, number = {4}, pages = {417-425}, pmid = {24454464}, issn = {1738-6756}, abstract = {PURPOSE: Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC.

METHODS: We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010.

RESULTS: Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692).

CONCLUSION: Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.}, } @article {pmid24454462, year = {2013}, author = {Min, Y and Bae, SY and Lee, HC and Lee, JH and Kim, M and Kim, J and Lee, SK and Kil, WH and Kim, SW and Lee, JE and Nam, SJ}, title = {Tubular carcinoma of the breast: clinicopathologic features and survival outcome compared with ductal carcinoma in situ.}, journal = {Journal of breast cancer}, volume = {16}, number = {4}, pages = {404-409}, pmid = {24454462}, issn = {1738-6756}, abstract = {PURPOSE: Tubular carcinoma (TC) of the breast is an uncommon histological subtype of invasive breast cancer with an excellent prognosis compared with standard invasive ductal carcinoma. Recent studies suggested a possible precursor role for low grade ductal carcinoma in situ (DCIS) in the development of TC. The goal of this analysis was to understand the clinicopathologic features and outcomes of TC by comparing TC with DCIS.

METHODS: A retrospective review identified 70 patients with TC and 1,106 patients with DCIS between 1995 and 2011. Student t-test and Fisher exact test were used to compare the clinicopathologic characteristics of TC patients with those of DCIS patients. The Kaplan-Meier method and Cox regression analysis were used to determine disease-free survival (DFS) rates.

RESULTS: Compared to DCIS, TC exhibited favorable clinicopathologic characteristics such as a lower nuclear grade (92.3%), higher expression of hormonal receptors (estrogen receptor-positive, 92.9%; progesterone receptor-positive, 87.0%), and less frequent overexpression of human epidermal growth receptor 2 (12.9%). DFS did not differ significantly between the TC and DCIS groups (5-year DFS, 100% vs. 96.7%; 10-year DFS, 92.3% vs. 93.3%; p=0.324), and cancer-specific deaths were not noted in either group. However, axillary lymph node involvement was observed in six (8.6%) of the 70 patients with TC. Three of these patients had small tumors (≤1 cm).

CONCLUSION: In our study cohort, TC was associated with an excellent prognosis and a low rate of lymph node metastasis. However, lymph nodes metastases were found even in patients with small tumors (≤1 cm). Axillary staging must be considered for all patients with TC of the breast.}, } @article {pmid24451159, year = {2014}, author = {Peressin, M and Proust, A and Schmidt, S and Su, B and Lambotin, M and Biedma, ME and Laumond, G and Decoville, T and Holl, V and Moog, C}, title = {Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells and macrophages to autologous T lymphocytes.}, journal = {AIDS (London, England)}, volume = {28}, number = {5}, pages = {667-677}, doi = {10.1097/QAD.0000000000000193}, pmid = {24451159}, issn = {1473-5571}, mesh = {CD4-Positive T-Lymphocytes/*virology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/*virology ; Flow Cytometry ; HIV Core Protein p24/analysis ; HIV Infections/*virology ; HIV-1/*isolation & purification ; Humans ; Infant, Newborn ; Macrophages/*virology ; Time Factors ; }, abstract = {OBJECTIVE: The chronology of HIV infection in mucosal tissue after sexual transmission is unknown. Several potential HIV target cells are present at these sites, including dendritic cells, macrophages, and CD4(+) T lymphocytes. Dendritic cells and macrophages are antigen-presenting cells (APCs) and are thus involved in cross-talk with T cells. This close contact may favor efficient HIV-1 transfer to T lymphocytes, resulting in rapid HIV-1 dissemination.

DESIGN: We investigated the role of APCs in HIV transfer to T cells by incubating Langerhans cells and interstitial dendritic cells (IDCs) or monocyte-derived macrophages (MDMs) with HIV for 2 h before addition of uninfected autologous CD4(+) T lymphocytes.

METHODS: HIV infection was recorded after different time points. Following staining, the measurement of intracellular p24 in the different cell populations was analyzed by flow cytometry.

RESULTS: We showed that Langerhans cells/IDCs and macrophages efficiently transferred HIV to CD4(+) T cells. Interestingly, a rapid HIV transfer in trans predominated in MDMs, whereas cis transfer mainly occurred in Langerhans cells/IDC cocultures. Neutralizing antibody 2G12, added to HIV-loaded APCs, efficiently blocked both the trans and the cis infection of T cells.

CONCLUSION: These findings highlight the major contributions of various mucosal cells in HIV dissemination and suggest that HIV hijacks the different properties of APCs to favor its dissemination through the body. They emphasize the role of macrophages in the rapid transmission of HIV to T lymphocytes at mucosal sites, dendritic cells being prone to migration to lymphoid organ for subsequent dissemination by cis transfer.}, } @article {pmid24449868, year = {2014}, author = {Huang, B and Omoto, Y and Iwase, H and Yamashita, H and Toyama, T and Coombes, RC and Filipovic, A and Warner, M and Gustafsson, JÅ}, title = {Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {5}, pages = {1933-1938}, pmid = {24449868}, issn = {1091-6490}, support = {12011/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Carcinoma, Lobular/metabolism/pathology ; Epithelium/metabolism/pathology ; Estrogen Receptor alpha/*metabolism ; Estrogen Receptor beta/*metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; }, abstract = {The role of estrogen receptor (ER) α as a target in treatment of breast cancer is clear, but those of ERβ1 and ERβ2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ERα was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ERβ. We found that whereas ductal cancer is a highly proliferative, ERα-positive, ERβ-negative disease, lobular cancer expresses both ERα and ERβ but with very few Ki67-positive cells. ERβ2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ERβ2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1α. ERβ2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERα nor ERβ was expressed, but in the high-grade lobular cancer ERβ was lost and ERα and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ERβ agonists in preventing in situ ductal cancers from becoming invasive.}, } @article {pmid24445272, year = {2014}, author = {Yoon, HJ and Sung, SH and Moon, BI and Kim, BS}, title = {Invasive ductal carcinoma arising from dense accessory breast visualized with 99mTc-MIBI breast-specific γ imaging.}, journal = {Clinical nuclear medicine}, volume = {39}, number = {8}, pages = {717-720}, doi = {10.1097/RLU.0000000000000332}, pmid = {24445272}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/*diagnostic imaging/pathology ; Female ; Humans ; Neoplasm Invasiveness/diagnostic imaging ; Radionuclide Imaging ; *Radiopharmaceuticals ; *Technetium Tc 99m Sestamibi ; }, abstract = {Primary accessory breast cancer is extremely rare, and the diagnostic efficacy of Tc-MIBI breast-specific γ imaging (BSGI) has not been reported elsewhere. We present a case of primary carcinoma arising from dense accessory breast that was visualized with BSGI. A 43-year-old female patient with a palpable axillary mass underwent mammography, which showed dense parenchyma on both of the anatomic and accessory breasts with no abnormality. Subsequent BSGI showed no abnormal uptake in bilateral anatomic breasts, but focal abnormal uptake was noted in the accessory breast. Permanent pathologic evaluation confirmed invasive ductal carcinoma (not otherwise specified type) of the accessory breast.}, } @article {pmid24429935, year = {2014}, author = {Agarwal, S and Pappas, L and Neumayer, L and Kokeny, K and Agarwal, J}, title = {Effect of breast conservation therapy vs mastectomy on disease-specific survival for early-stage breast cancer.}, journal = {JAMA surgery}, volume = {149}, number = {3}, pages = {267-274}, doi = {10.1001/jamasurg.2013.3049}, pmid = {24429935}, issn = {2168-6262}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/pathology/radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy/*mortality ; Mastectomy, Segmental/mortality ; Middle Aged ; Multivariate Analysis ; Propensity Score ; Proportional Hazards Models ; SEER Program ; Survival Analysis ; }, abstract = {IMPORTANCE: To our knowledge, there are no recent studies that directly compare survival after breast conservation therapy (BCT) vs mastectomy.

OBJECTIVE: To compare the breast cancer-specific survival rates of patients undergoing BCT, mastectomy alone, or mastectomy with radiation using a contemporary cohort of patients.

We performed univariate, multivariate logistic regression, and propensity analyses to compare the hazard of death for female patients with early-stage invasive ductal carcinoma treated with BCT, mastectomy alone, or mastectomy with radiation during the period from 1998 to 2008. The data were extracted from the Surveillance, Epidemiology, and End Results database. Early-stage breast cancer was defined as having a tumor size of 4 cm or smaller with 3 or less positive lymph nodes.

EXPOSURE: Breast conservation therapy, mastectomy alone, or mastectomy with radiation.

MAIN OUTCOMES AND MEASURES: Hazard of death due to breast cancer for patients undergoing BCT, mastectomy alone, or mastectomy with radiation.

RESULTS: A total of 132,149 patients were included in this analysis. Breast conservation therapy was used to treat 70% of patients, mastectomy alone was used to treat 27% of patients, and mastectomy with radiation was used to treat 3% of patients. The 5-year breast cancer-specific survival rates of patients who underwent BCT, a mastectomy alone, or a mastectomy with radiation were 97%, 94%, and 90%, respectively (P < .001); the 10-year breast cancer-specific survival rates were 94%, 90%, and 83%, respectively (P < .001). Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001). When propensity score stratification was used, the effect of treatment method on survival was similar.

CONCLUSIONS AND RELEVANCE: Patients who underwent BCT have a higher breast cancer-specific survival rate compared with those treated with mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma. Further investigation is warranted to understand what may be contributing to this effect.}, } @article {pmid24425047, year = {2014}, author = {Sikora, MJ and Cooper, KL and Bahreini, A and Luthra, S and Wang, G and Chandran, UR and Davidson, NE and Dabbs, DJ and Welm, AL and Oesterreich, S}, title = {Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.}, journal = {Cancer research}, volume = {74}, number = {5}, pages = {1463-1474}, pmid = {24425047}, issn = {1538-7445}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; P30CA047904/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Breast Neoplasms/drug therapy/genetics/metabolism ; Carcinoma, Lobular/*drug therapy/*genetics/metabolism ; Cell Line, Tumor ; Estrogens/*genetics/metabolism ; Female ; Gene Expression/drug effects/*genetics ; Humans ; MCF-7 Cells ; Middle Aged ; Receptor, Fibroblast Growth Factor, Type 1/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Signal Transduction/drug effects/genetics ; Tamoxifen/*pharmacology ; }, abstract = {Invasive lobular carcinoma (ILC) is a histologic subtype of breast cancer that is frequently associated with favorable outcomes, as approximately 90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that patients with ILC receiving adjuvant endocrine therapy may not benefit as much as patients with invasive ductal carcinoma. On the basis of these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome via gene expression microarray analyses and ER ChIP-Seq, and to examine response to endocrine therapy. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. We identified 915 genes that were uniquely E2 regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also E2 regulated in vivo in HCI-013. MM134 cells were de novo tamoxifen resistant and were induced to grow by 4-hydroxytamoxifen, as well as other antiestrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required fibroblast growth factor receptor (FGFR)-1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.}, } @article {pmid24419371, year = {2013}, author = {Vucicevic, D and Carey, EJ and Karlin, NJ}, title = {Trastuzumab-induced hepatotoxicity: a case report.}, journal = {Breast care (Basel, Switzerland)}, volume = {8}, number = {2}, pages = {146-148}, pmid = {24419371}, issn = {1661-3791}, abstract = {BACKGROUND: Trastuzumab is a humanized monoclonal antibody approved for the treatment of breast cancer with HER2 amplification and/or overexpression. There are only 2 prior cases of trastuzumab-related hepatotoxicity reported in the literature.

CASE REPORT: We report the case of a 60-year-old woman who was treated with trastuzumab for stage I invasive ductal carcinoma of the right breast. She successfully completed 6 months of therapy when an increase in liver transaminases was noted on routine examination. A full work-up for causes of acute and chronic liver disease was negative. After review of the patient's medication list, trastuzumab was thought to be the most likely culprit for the liver injury, based on timing of administration and rise in liver enzymes.}, } @article {pmid24411296, year = {2014}, author = {Benkerroum, Z and Babahabib, A and Kouach, J and Chahdi, H and Al Bouzidi, A and Moussaoui Rehali, D and Dehayni, M}, title = {[Metrorrhagia disclosing a synchronous bilateral breast cancer: report of a case].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {42}, number = {5}, pages = {360-364}, doi = {10.1016/j.gyobfe.2013.11.009}, pmid = {24411296}, issn = {1769-6682}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Metrorrhagia/*etiology ; Middle Aged ; Neoplasms, Multiple Primary/pathology ; Uterine Cervical Neoplasms/diagnosis/*secondary ; }, abstract = {Genital metastases are very rarely indicative of breast cancer; they are exceptionally located at the cervix. These atypical locations are more common when it comes to a metastatic breast cancer or a histological infiltrating lobular type. The simultaneous association of a lobular and a ductal infiltrating cancer under a synchronous bilateral breast cancer still remains a rare entity. In this work, we report the observation of a woman aged 48 who has a synchronous bilateral breast cancer, of different histological types, and who reported at first a genital bleeding which is caused by a metastasis in the cervix of the uterus.}, } @article {pmid24403473, year = {2014}, author = {González-Sistal, A and Sánchez, AB and Del Rio, MC and Arias, JI and Herranz, M and Ruibal, A}, title = {Association between tumor size and immunohistochemical expression of Ki-67, p53 and BCL2 in a node-negative breast cancer population selected from a breast cancer screening program.}, journal = {Anticancer research}, volume = {34}, number = {1}, pages = {269-273}, pmid = {24403473}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/epidemiology/metabolism/*pathology ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/*metabolism ; Lymph Nodes/metabolism/*pathology ; Middle Aged ; Neoplasm Grading ; Pregnancy ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND/AIM: Breast cancer is the most common type of cancer among women. Breast infiltrating ductal carcinoma (IDC) is the most common type of breast cancer, approximately 80% of all breast carcinomas. The aim of this study was to analyze the association of tumor size, evaluated after histopathological analysis, with different clinical and biological parameters in IDC.

MATERIALS AND METHODS: The study group included 251 women with IDC without axillary lymph node involvement, aged between 27 and 81 years. Analyzed parameters were: age, histological grade, menopausal status, menarche, pregnancy, abortion, breastfeeding, contraceptive use, hormone replacement therapy, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Ki-67, p53 and BCL2.

RESULTS: Pathological tumor size was between 0.2 and 5.1 cm (1.43±0.86 cm). Tumors in 45 cases exceeded 2 cm, in eight 3 cm and only in one 5 cm. Pathological size was significantly associated with age >70 vs. <50 years (p=0.054), histological grade III vs. I (p=0.0003), positivity for Ki-67 (p=0.0003) and for p53 (p=0.0032).

CONCLUSION: Tumor size was significantly associated with age >70 years, histological grade 3 and immunohistochemically-augmented expression of Ki-67 and p53.}, } @article {pmid24401140, year = {2014}, author = {Tukenmez, M and Ozden, BC and Agcaoglu, O and Kecer, M and Ozmen, V and Muslumanoglu, M and Igci, A}, title = {Videoendoscopic single-port nipple-sparing mastectomy and immediate reconstruction.}, journal = {Journal of laparoendoscopic & advanced surgical techniques. Part A}, volume = {24}, number = {2}, pages = {77-82}, pmid = {24401140}, issn = {1557-9034}, mesh = {Adult ; Axilla/surgery ; Breast Implants ; Breast Neoplasms/surgery ; Carcinoma in Situ/surgery ; Carcinoma, Ductal/surgery ; Endoscopy/instrumentation/*methods ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision/methods ; Mammaplasty/*methods ; Mastectomy/*methods ; Middle Aged ; Neoplasm Recurrence, Local ; Nipples/*surgery ; Organ Sparing Treatments/*methods ; Retrospective Studies ; Video-Assisted Surgery/*methods ; }, abstract = {PURPOSE: Single-incision videoendoscopic surgery has recently become popular as a result of the ongoing search for less invasive procedures. The aim of this study was to evaluate the safety and efficacy of endoscopic single-port nipple-sparing mastectomy, axillary lymphadenectomy, and immediate reconstruction in patients with breast cancer.

PATIENTS AND METHODS: From May 14, 2012 through January 23, 2013, 10 patients underwent videoendoscopic single-port nipple-sparing mastectomy and axillary dissection via a single, limited incision and immediate prosthetic reconstruction. Patient charts were reviewed, and demographic data, operative time, complications and pathology results were analyzed.

RESULTS: In all patients, videoendoscopic surgery was performed successfully. Of 10 patients, 7 were diagnosed as having invasive ductal carcinoma, 2 had a ductal carcinoma in situ, and 1 underwent bilateral prophylactic mastectomy. The weight of the resected gland was 300-650 g, with a mean of 420 g. There were no operative complications, and the mean operative time was 250 minutes (range, 160-330 minutes). One-stage reconstruction with implants was performed on 4 patients, whereas expanders were placed in the remaining 6. Surgical margins of all cases were pathologically negative, and there were no recurrences observed during the early follow-up period.

CONCLUSIONS: Videoendoscopic single-port nipple-sparing mastectomy is technically feasible even in larger breasts, enabling immediate reconstruction with good cosmetic outcomes. However, further studies with larger clinical series and long-term follow-up are required to compare the safety and efficacy of the technique with those of the standard nipple-sparing mastectomy.}, } @article {pmid24401026, year = {2014}, author = {Mangal, JP and Rimland, D and Marconi, VC}, title = {The continuum of HIV care in a Veterans' Affairs clinic.}, journal = {AIDS research and human retroviruses}, volume = {30}, number = {5}, pages = {409-415}, pmid = {24401026}, issn = {1931-8405}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; }, mesh = {Continuity of Patient Care/*organization & administration ; Cross-Sectional Studies ; Female ; HIV Infections/*diagnosis/*drug therapy ; Humans ; Male ; Middle Aged ; *Outpatient Clinics, Hospital ; United States ; *Veterans ; }, abstract = {The cascade of HIV care in the United States has become a focus for interventions aimed at improving the success of HIV treatment. The Atlanta VA Medical Center (AVAMC) Infectious Disease Clinic (IDC) is an urban clinic that provides care for over 1,400 people living with HIV (PLHIV) annually. Using data from the HIV Atlanta VA Cohort Study (HAVACS), we modeled the continuum of care in the AVAMC IDC and explored similarities and differences with national models. We conducted a cross-sectional analysis of 1,474 individuals receiving care in the AVAMC IDC. We estimated total PLHIV and defined several categories within the spectrum of HIV care. We then developed the continuum of care using two methodologies. The first required each stage to be a dependent subset of the immediate upstream stage. The second allowed each stage to be independent of upstream stages. Dependent stage categorization estimated that 95.3% of individuals were diagnosed with HIV, 89.8% of individuals were linked to care, 73.0% of individuals were retained in care, 65.9% of individuals were eligible for antiretroviral treatment (ART), 62.8% were prescribed ART, and 52.4% had a suppressed viral load (VL). Independent stage categorization estimated that 83.9% of individuals were prescribed ART and 61.5% had a suppressed VL. Our analyses showed that the AVAMC IDC estimates were significantly better than national estimates at every stage. This may reflect the benefits of a universal healthcare system. We propose the use of independent stages for the continuum as this more accurately represents healthcare utilization.}, } @article {pmid24400686, year = {2014}, author = {Shin, YD and Lee, SK and Kim, KS and Park, MJ and Kim, JH and Yim, HS and Choi, YJ}, title = {Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.}, journal = {World journal of surgical oncology}, volume = {12}, number = {}, pages = {5}, pmid = {24400686}, issn = {1477-7819}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Inflammatory Breast Neoplasms/*pathology/surgery ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/surgery ; Phyllodes Tumor/*pathology/surgery ; Prognosis ; }, abstract = {There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.}, } @article {pmid24396451, year = {2014}, author = {Ishida, M and Umeda, T and Kawai, Y and Mori, T and Kubota, Y and Abe, H and Iwai, M and Yoshida, K and Kagotani, A and Tani, T and Okabe, H}, title = {Mucinous carcinoma occurring in the male breast.}, journal = {Oncology letters}, volume = {7}, number = {2}, pages = {378-380}, pmid = {24396451}, issn = {1792-1074}, abstract = {Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.}, } @article {pmid24394860, year = {2014}, author = {Popiel, B and Gupta, D and Misra, S}, title = {Value of an intraoperative real time tissue perfusion assessment system following a nipple-sparing radical mastectomy for advanced breast cancer.}, journal = {International journal of surgery case reports}, volume = {5}, number = {1}, pages = {30-33}, pmid = {24394860}, issn = {2210-2612}, abstract = {INTRODUCTION: Standard surgical approach for advanced breast cancer is a modified radical mastectomy with a periareolar elliptical incision. Here a unique surgical approach is presented utilizing intraoperative real time tissue perfusion technology.

PRESENTATION OF CASE: A 65-year old African American female was diagnosed with grade 3 papillary carcinoma on biopsy of a palpable 3.7cm left breast mass at 12 o'clock position. Pathology showed a T2N0M0 invasive ductal carcinoma, triple negative disease, with clear margins. Patient opted for naturopathic treatment. Six months later, cancer recurred at the local site; the patient persisted with natural remedies. Nine months later, the mass had progressed to 14.5cm with smaller adjacent nodules and nodular thickening of breast with no metastatic disease. Patient received neoadjuvant chemoradiation. Ten months later, patient underwent a nipple-sparing radical mastectomy given the persistent pectoral muscle involvement of this mass.

DISCUSSION: An elliptical incision was made in the superior aspect of the breast wall at least 6cm above the areola. After tumor removal, the skin edges were approximated. It was decided preoperatively to use the SPY Elite™ system to assess perfusion of the flap edges. Angiography with indocyanine green showed poor perfusion of the inferior flap and an additional 2cm of skin was resected. Final pathology showed that all margins were clear of disease and patient recovered well from surgery.

CONCLUSION: This case study shows that an individualized approach resulted in an optimal outcome for the patient. The infrequent procedure of a nipple-sparing radical mastectomy was done in coordination with SPY Elite™ to achieve good wound healing.}, } @article {pmid24394137, year = {2013}, author = {Kameyama, A and Noda, T and Hatano, H and Dono, K and Oshima, K and Miyake, M and Komori, T and Kawanishi, K and Imamura, H and Morita, S and Iwazawa, T and Akagi, K and Kitada, M}, title = {[A case of a patient with giant mucinous cystadenocarcinoma who presented with abdominal pain].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2437-2440}, pmid = {24394137}, issn = {0385-0684}, mesh = {Abdominal Pain/*etiology ; Adult ; Cystadenocarcinoma, Mucinous/complications/*surgery ; Female ; Humans ; Neoplasm Invasiveness ; Pancreatic Neoplasms/complications/*pathology/surgery ; Treatment Outcome ; }, abstract = {We report a case of a patient in whom a giant mucinous cystadenocarcinoma was treated with distal pancreatectomy. A 37-year-old woman was admitted to the hospital complaining of intermittent epigastric pain. The laboratory data revealed a marked increase in serum levels of carcinoembryonic antigen(CEA 22 ng/mL), cancer antigen(CA) 19-9(258,129 U/ mL), and CA125 (53 U/mL). A computed tomography (CT) scan revealed a cystic tumor, 15 cm in diameter, in the body of the pancreas. The tumor presented as a multilocular cyst with enhanced nodules. On positron emission tomography (PET)-CT,[ 18F] fluorodeoxyglucose uptake by the nodules of the cyst was noted. Under the diagnosis of malignant mucinous cystic neoplasm, we performed distal pancreatectomy, splenectomy, partial gastrectomy, and left adrenalectomy because the tumor was suspected to be invading the stomach and left adrenal gland. The tumor was histologically diagnosed as invasive mucinous cystadenocarcinoma with ovarian-like stroma. The patient survived for 14 months after surgery without tumor recurrence. Invasive mucinous cystadenocarcinoma of the pancreas has high rates of lymph node metastasis and early recurrence after surgery. We believe that we would have had to perform complete tumor resection equivalent to that of invasive ductal carcinoma of the pancreas if the mucinous cystic neoplasm was found to be malignant preoperatively.}, } @article {pmid24394131, year = {2013}, author = {Oshida, S and Hayashi, K and Habiro, T and Hatate, K and Sengoku, N}, title = {[A case of acute appendicitis which occurred during chemotherapy for breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2417-2419}, pmid = {24394131}, issn = {0385-0684}, mesh = {Acute Disease ; Adenocarcinoma, Scirrhous/*drug therapy/surgery ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Appendicitis/complications/*surgery ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Docetaxel ; Female ; Humans ; Mastectomy, Segmental ; Sentinel Lymph Node Biopsy ; Taxoids/administration & dosage ; }, abstract = {The patient was a 66-year-old woman with left breast cancer who underwent left segmental mastectomy with sentinel lymph node biopsy. The histopathological diagnosis was estrogen receptor-positive (ER+), progesterone receptor-positive(PgR+), human epidermal growth factor receptor-2-equivocal(HER2()2+)(with no HER2 gene amplification by fluorescence in-situ hybridization analysis) invasive ductal carcinoma (scirrhous carcinoma) with Ki-67 expression of less than 10% (pathological T1c, N0, M0, stage I). The patient requested chemotherapy, and 4 cycles of docetaxel plus cyclophosphamide (TC) were scheduled. Fever and epigastric pain developed on day 13 of cycle 2. On day 22, the patient was examined before the third cycle of TC, and right lower abdominal pain was reported. Computed tomography revealed appendicitis and an intraperitoneal abscess. She was admitted to the hospital and underwent partial ileocecal resection. The patient was discharged on the 12th postoperative day with no further complications. Acute abdomen during chemotherapy for malignant tumors has been reported sporadically in patients with leukemia. A diagnosis of acute abdomen in patients undergoing cancer treatment requires careful assessment of gastrointestinal symptoms such as nausea and vomiting during chemotherapy, fever associated with granulocytopenia, and findings indicative of local inflammation. The patient in this case recovered uneventfully because imaging studies and surgery were performed promptly after presentation.}, } @article {pmid24394130, year = {2013}, author = {Nagashima, S and Sakurai, K and Suzuki, S and Hara, Y and Waga, E and Hirano, T and Enomoto, K and Fujisaki, S and Amano, S and Koshinaga, T}, title = {[Successful treatment of multiple breast tumors with breast-conserving surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2414-2416}, pmid = {24394130}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/pathology/*surgery ; Female ; Fibroadenoma/*surgery ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {We report a case in which we were able to treat multiple tumors in the right breast with breast-conserving surgery. The patient was a 60-year-old woman in whom mammography revealed grouped round calcifications and distortion in the right breast. The tumor was not palpable. Ultrasonography revealed 3 tumors in the patient's right breast. One tumor, 14.5 mm in diameter, was located in the AC area of her right breast. Vacuum-assisted core-needle biopsy was performed on this tumor, and histopathological examination revealed invasive ductal carcinoma of the breast. The tumor was estrogen receptor (ER)-positive, progesterone receptor(PgR)-negative, and human epidermal growth factor receptor(HER)-2-positive. Another tumor, 5.5 mm in diameter, was located in the C area of the patient's right breast. This tumor was diagnosed as a satellite lesion of the tumor in the AC area. The third tumor, 19.0 mm in diameter, was located in the A area of the patient's right breast. This tumor was expected to be a fibroadenoma on the basis of the clinical findings. We performed breast-conserving surgery to remove these 3 tumors and biopsied the sentinel lymph nodes. Intra-operative rapid pathological diagnosis indicated that the surgical margins were negative and the sentinel lymph nodes were negative for metastasis. The final pathological diagnosis was the same as the preoperative diagnosis.}, } @article {pmid24394129, year = {2013}, author = {Toyoda, Y and Hojo, S and Yoshioka, S and Kojima, F and Matsunaga, H and Fujie, Y and Fukunaga, H and Ota, H and Endo, W and Maeura, Y}, title = {[A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2411-2413}, pmid = {24394129}, issn = {0385-0684}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/*pathology/radiotherapy/surgery ; *Carcinoma, Ductal/radiotherapy/surgery ; Combined Modality Therapy ; Female ; Humans ; *Phyllodes Tumor/radiotherapy/surgery ; Treatment Outcome ; }, abstract = {A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width(D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.}, } @article {pmid24394126, year = {2013}, author = {Okishiro, M and Egawa, C and Kusama, H and Matsushita, K and Hashimoto, T and Mukai, Y and Kawashima, H and Hamanaka, M and Takeno, A and Sakisaka, H and Nakahira, S and Taniguchi, K and Suzuki, R and Takeda, Y and Kato, T and Tamura, S and Takatsuka, Y}, title = {[Analysis of elderly breast cancer patients aged 90 years and older].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2402-2404}, pmid = {24394126}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/surgery/*therapy ; Carcinoma, Ductal, Breast/surgery/therapy ; Combined Modality Therapy ; Humans ; Lymphatic Metastasis ; Retrospective Studies ; }, abstract = {In recent years, although the number of elderly patients with breast cancer is increasing, there are very few reports of breast cancer in elderly patients aged 90 years and older. In this study, we examined breast cancer patients who were 90 years of age or older. Patient background characteristics, clinicopathologic features, and treatment strategies were examined for 9 elderly breast cancer patients aged 90 or older who were treated at our department from January 2000 to December 2012. The median age of the patients was 91 (range, 90-99)years, and complications were reported in 7 patients (77.8%). The median tumor diameter was 4.3 (range, 1.4-6.0) cm, and T4 disease was observed in 6 patients (66.7%). Axillary lymph node status was negative in 6 patients (66.7%). Pathological diagnoses were invasive ductal carcinoma in 8 patients and ductal carcinoma in situ in 1 patient. Seven patients were hormone receptor positive and 1 patient was hormone receptor negative. Human epidermal growth factor receptor (HER)-2 status was negative in 8 patients. Surgery was performed safely in 5 patients and there were no signs of postoperative metastases. Four patients were treated with hormone therapy. The response rate(partial response[ PR] and complete response[ CR]) was 50%. Our findings suggest that when treating breast cancer patients aged 90 years or older, it would be necessary to offer medical treatment considering the possibility of comorbidities and the complications associated with medical treatment.}, } @article {pmid24394125, year = {2013}, author = {Ueno, S and Miyauchi, K and Nakakuma, T and Kurita, A and Mineta, S and Mizutani, T and Yamamoto, K and Jin, M and Inada, H and Oshima, H and Kobayashi, I and Bizen, A}, title = {[A case of locally advanced breast cancer successfully treated with Mohs paste].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2399-2401}, pmid = {24394125}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Chlorides/*therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Quality of Life ; Zinc Compounds/*therapeutic use ; }, abstract = {We report a case of primary advanced breast cancer that was locally controlled by treatment with Mohs paste. A 57- year-old woman presented with right locally advanced breast cancer with massive exudate and oozing blood. Histopathological examination indicated an invasive ductal carcinoma. Moreover, the patient had lung, liver, and bone metastases. She received chemotherapy, following which the breast tumor was treated using Mohs paste and dissected. The bleeding and exudate stopped almost completely, and the breast tumor became flat. Therefore, it is suggested that locally advanced breast cancer could be controlled by treatment with Mohs paste.}, } @article {pmid24394124, year = {2013}, author = {Yabe, N and Murai, S and Shimizu, H and Kitasato, K and Yoshikawa, T and Oto, I and Nakadai, J and Jinno, H and Kitagawa, Y}, title = {[A case of effective trastuzumab plus gemcitabine therapy for human epidermal growth factor receptor 2-positive breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2396-2398}, pmid = {24394124}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/surgery ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Humans ; Receptor, ErbB-2/analysis ; Trastuzumab ; Gemcitabine ; }, abstract = {A 71-year-old postmenopausal woman was undergoing treatment for depression. She visited the hospital with a chief complaint of fibrosclerosis of the entire left breast 8 years previously. She was diagnosed as having stage IV(T3N1M1b) left breast cancer (papillotubular>scirrhous carcinoma, g+, f+, estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2[ HER2/neu]-positive[ 3+]). Synchronous bone metastases were detected in the left tenth rib, the eleventh dorsal vertebra, and in the area spanning the lower lumbar to sacral vertebrae. First-line treatment was systemic therapy with 4 cycles of Adriamycin and cyclophosphamide (AC) followed by 4 cycles of trastuzumab and paclitaxel. The breast mass initially observed on clinical imaging disappeared and only calcifications were observed. Bone metastases were detected only in the left tenth rib. As an additional therapy, 3-dimensional radiotherapy(50 Gy/25 fractions), which irradiated the left mammary gland, axilla, and supraclavicular fossa, was administered. The tumor was well controlled for approximately 3 years. However, a gradual increase in the level of carcinoembryonic antigen(CEA) was accompanied by an increase in the left breast mass and enlargement of left axillary lymph nodes. Modified radical mastectomy (Bt+Ax [level I]) was performed for this condition 3 years ago. Papillotubular-type invasive ductal carcinoma (INF β, ly3, v0, g+, f+, s+, nuclear grade 3 [atypia 3+mitosis 3]) was diagnosed histopathologically. Lymph node metastases were also detected. As histopathological examination of the bone metastatic lesion showed no progression, administration of lapatinib and capecitabine was initiated. After 15 cycles of treatment, enlarged right axillary lymph nodes were observed and local excision was performed. Histopathological examination revealed recurrence of the breast cancer. The patient was diagnosed as having grade 3(atypia 3, mitosis 2) breast cancer(ER-negative, PgR-negative, HER2/neu positive[ 3+], and MIB-1 index 50%). The response to treatment with lapatinib and capecitabine was progressive disease(PD), and therefore, trastuzumab and gemcitabine therapy was selected. Currently, the patient has undergone 30 cycles of this regimen and the tumor is well controlled. This regimen was considered effective for the treatment of patients with HER2-positive metastatic breast cancer.}, } @article {pmid24394122, year = {2013}, author = {Hagino, S and Iwata, K and Nakura, M and Yoshizumi, T and Tsuneda, A and Kiriyama, M}, title = {[A case of recurrent breast cancer that responded to bevacizumab].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2390-2392}, pmid = {24394122}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Recurrence ; }, abstract = {We report a case of a 59-year-old woman who was forced to undergo mastectomy of the right breast (Rt Bt) plus axillary lymph node (Ax) dissection for right breast cancer at another hospital. The pathological diagnosis was invasive ductal carcinoma(scirrhou[s sci], pT2N2M0, Stage IIIA, estrogen recepto[r ER[]+], progesterone recepto[r PgR[]+], human epidermal growth factor receptor-2[HER2][2+]). Although no recurrence was observed after postoperative adjuvant chemotherapy and endocrine therapy, skin metastasis on the left back and pleuritis carcinomatosa were detected at our hospital 9 years and 6 months after the operation. Thereafter, bone metastasis, contralateral lymph node metastasis, and frequent occurrence of hepatic metastasis were sequentially detected. The patient was treated with chemotherapy (a total of 4 regimens) and endocrine therapy in addition to radiation therapy for lymph node metastasis over a period of approximately 2 years and 3 months; however, disease control was poor. Therefore, combined chemotherapy with paclitaxel and bevacizumab was initiated from February 2012. Soon after the initiation of combination therapy, the serum carcinoembryonic antigen (CEA) level gradually reduced and computed tomography (CT) revealed that the multiple-organ metastases had remarkably reduced in size. The response was classified as a clinical partial response (cPR). Although adverse events such as peripheral neuropathy, nose bleeding, and high blood pressure were observed, these were all of lesser that Grade 2 severity. The efficacy of chemotherapy was noted for 11 months.}, } @article {pmid24394112, year = {2013}, author = {Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Enomoto, K and Amano, S}, title = {[Diagnosis of ductal carcinoma in situ with interruption of the anterior border of the mammary gland by ultrasonography-a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {12}, pages = {2360-2362}, pmid = {24394112}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mammary Glands, Human/*pathology ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; Tamoxifen/therapeutic use ; Ultrasonography ; }, abstract = {We report a case of ductal carcinoma in situ(DCIS) with interruption of the anterior border of the mammary gland by ultrasonography. The patient was a 41-year-old woman. The patient was identified by a focal asymmetric density on her left breast by screening mammography. Ultrasonography showed an ill-defined low echoic mass, 25 mm in diameter, in the A area of her left breast. The tumor had features consistent with the interruption of the anterior border of the mammary gland. Therefore, she was diagnosed with invasive ductal carcinoma of the breast. We performed a modified radical mastectomy with sentinel lymph node biopsy. A resected specimen led to a diagnosis of DCIS positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. After surgery, she was administered tamoxifen. One year and 6 months after the operation, she is well without metastases. Ultrasonography is generally useful to differentiate between a DCIS lesion or an invasive ductal carcinoma lesion. However, in this case, we could not diagnose the tumor as DCIS by ultrasonography because the tumor was interrupted by the anterior border of the mammary gland. This case suggests that we should be cautious when diagnosing low echoic tumors with interruption of the anterior border of the mammary gland by ultrasonography.}, } @article {pmid24393444, year = {2014}, author = {Willekens, I and Van de Casteele, E and Buls, N and Temmermans, F and Jansen, B and Deklerck, R and de Mey, J}, title = {High-resolution 3D micro-CT imaging of breast microcalcifications: a preliminary analysis.}, journal = {BMC cancer}, volume = {14}, number = {}, pages = {9}, pmid = {24393444}, issn = {1471-2407}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Calcinosis/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Female ; Humans ; *Imaging, Three-Dimensional ; Mammography/*methods ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; *Radiographic Image Interpretation, Computer-Assisted ; *X-Ray Microtomography ; }, abstract = {BACKGROUND: Detection of microcalcifications on mammograms indicates the presence of breast lesion, and the shapes of the microcalcifications as seen by conventional mammography correlates with the probability of malignancy. This preliminary study evaluated the 3D shape of breast microcalcifications using micro-computed tomography (micro-CT) and compared the findings with those obtained using anatomopathological analysis.

METHODS: The study analyzed breast biopsy samples from 11 women with findings of suspicious microcalcifications on routine mammograms. The samples were imaged using a micro-CT (SkyScan 1076) at a resolution of 35 μm. Images were reconstructed using filtered back-projection and analyzed in 3D using surface rendering. The samples were subsequently analyzed by the pathology service. Reconstructed 3D images were compared with the corresponding histological slices.

RESULTS: Anatomopathological analysis showed that 5 of 11 patients had ductal breast carcinoma in situ. One patient was diagnosed with invasive ductal carcinoma.Individual object analysis was performed on 597 microcalcifications. Malignant microcalcifications tended to be thinner and to have a smaller volume and surface area, while their surface area-to-volume ratio was greater than that of benign microcalcifications. The structure model index values were the same for malignant and benign microcalcifications.

CONCLUSIONS: This is the first study to use micro-CT for quantitative 3D analysis of microcalcifications. This high-resolution imaging technique will be valuable for gaining a greater understanding of the morphologic characteristics of malignant and benign microcalcifications. The presence of many small microcalcifications can be an indication of malignancy. For the larger microcalcifications, 3D parameters confirmed the more irregular shape of malignant microcalcifications.}, } @article {pmid24391224, year = {2013}, author = {Brakohiapa, EK and Armah, GE and Clegg-Lamptey, JN and Brakohiapa, WO}, title = {Pattern of breast diseases in Accra: review of mammography reports.}, journal = {Ghana medical journal}, volume = {47}, number = {3}, pages = {101-106}, pmid = {24391224}, issn = {2616-163X}, mesh = {Adult ; Age Distribution ; Aged ; Breast Neoplasms/complications/*diagnostic imaging ; Carcinoma, Ductal, Breast/complications/*diagnostic imaging ; *Early Detection of Cancer ; Female ; Ghana ; Humans ; *Mammography ; Middle Aged ; Pain/etiology ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVES: To document the mammographic patterns in females seeking medical attention in Accra.

DESIGN: An analytic retrospective study was conducted using data extracted from mammography request forms and corresponding radiological reports of 180 females.

SETTING: The radiology departments of Korle-Bu Teaching Hospital the Trust Hospital and Medical Imaging Ghana all located in Accra.

RESULTS: One hundred and eighty radiologic request forms for mammographic evaluations and their corresponding reports from the study period were reviewed. The mean age of the study population was 48.7 years (SD=10.0), and the median age group was the 41-50 group. There were more screening mammography evaluations (115 examinations) than diagnostic mammography evaluations (65 examinations). Most of the cases diagnosed as breast cancer were in the age group 41-50 years. Benign lesions were commoner than cancer (55 and 16 cases respectively). The commonest presenting complaint was of pain.

CONCLUSION: The larger number of screening mammographic evaluations conducted for asymptomatic females during the study period, as compared to diagnostic mammographic evaluations for symptomatic females, suggests that educational programs on early breast cancer detection are having a positive impact on the target population. The observation that 22.8% of lesions had features suggestive of breast cancer in the study is significantly high to also warrant intensification of the existing awareness programs. As non-specific masses were the most common radiographically observed lesions, hospitals equipped with sonography and biopsy facilities that compliment their mammography are better suited for thorough breast disease evaluation.}, } @article {pmid24388733, year = {2014}, author = {Guillot, E and Vaysse, C and Goetgeluck, J and Falcou, MC and Couturaud, B and Fitoussi, A and Fourchotte, V and Laki, F and Malhaire, C and Sigal-Zafrani, B and Sastre-Garau, X and Bollet, MA and Mosseri, V and Reyal, F}, title = {Extensive pure ductal carcinoma in situ of the breast: identification of predictors of associated infiltrating carcinoma and lymph node metastasis before immediate reconstructive surgery.}, journal = {Breast (Edinburgh, Scotland)}, volume = {23}, number = {2}, pages = {97-103}, doi = {10.1016/j.breast.2013.12.002}, pmid = {24388733}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*secondary/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mammaplasty/methods ; Middle Aged ; Risk Factors ; }, abstract = {AIM: To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS).

PATIENTS AND METHODS: Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% (n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded.

RESULTS: Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor (p = 0.002), high grade DCIS (p = 0.002) and detection of an opacity by mammography (p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 (p = 0.007), a palpable tumor (p = 0.012) and the detection of an opacity by mammography (p = 0.044) were associated with an increased rate of ALN involvement.

CONCLUSION: Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS.}, } @article {pmid24387825, year = {2014}, author = {Schleede, S and Bech, M and Grandl, S and Sztrókay, A and Herzen, J and Mayr, D and Stockmar, M and Potdevin, G and Zanette, I and Rack, A and Weitkamp, T and Pfeiffer, F}, title = {X-ray phase-contrast tomosynthesis for improved breast tissue discrimination.}, journal = {European journal of radiology}, volume = {83}, number = {3}, pages = {531-536}, doi = {10.1016/j.ejrad.2013.12.005}, pmid = {24387825}, issn = {1872-7727}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Feasibility Studies ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Mastectomy ; Pilot Projects ; Radiographic Image Enhancement/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods ; }, abstract = {PURPOSE: Attenuation-based tomosynthesis has proven to successfully resolve the glandular tissue overlap present in mammography. However, the ability of tomosynthesis to differentiate tumorous and glandular tissue remains limited, due to the small differences in X-ray attenuation in breast tissue. One possibility to overcome this limitation and to further increase the diagnostic value of tomosynthesis exams, is the application of recently developed grating-based phase-contrast methods, which provide complementary information on the phase shift and the local scattering power of the sample. In this study, we report on first phase-contrast breast tomosynthesis results of a mastectomy sample slice with an invasive ductal carcinoma.

MATERIAL AND METHODS: A slice of a mastectomy sample with histologically proven invasive ductal cancer was imaged at the synchrotron radiation source ESRF (Grenoble, France). We used a two-grating interferometer setup at the ninth fractional Talbot distance and with an X-ray energy of 23 keV. In grating interferometry absorption, differential phase, and scattering images are recorded simultaneously. The tomosynthesis scan comprises 61 projections. Multimodal tomosynthesis results were reconstructed using a standard filtered back-projection approach. Our findings are supported by a comparison of tomographic views to histopathology.

RESULTS: Phase-contrast tomosynthesis combines the advantage of improved soft-tissue discrimination in phase-contrast imaging with the ability of tomosynthesis to provide a third dimension so that improved feature visibility is not hampered by superposition artifacts. Our results indicate superior diagnostic value due to the depth resolution supplied in tomosynthesis imaging; a region of necrotic tissue that is obscured in a projection image can clearly be depicted in one single tomosynthesis slice. Compared to absorption tomosynthesis alone, soft tissue contrast is significantly enhanced in phase-contrast tomosynthesis views, where fibrous structures are clearly visible.

CONCLUSION: In this article we present the first proof-of-principle grating-based phase-contrast tomosynthesis of a mastectomy sample section. A comparison of conventional attenuation with phase-contrast and dark-field tomosynthesis indicates that complementary information from three signals yields an increase in diagnostic value, which is verified in a comparison of our results to histological sections of the sample. As grating-based phase-contrast mammography efficiently works with conventional lab sources, our benchmark results indicate the potential benefit of translating phase-contrast tomosynthesis into a clinical setting.}, } @article {pmid24384092, year = {2014}, author = {Tan, D and Chen, KE and Deng, C and Tang, P and Huang, J and Mansour, T and Luben, RA and Walker, AM}, title = {An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma.}, journal = {Cancer letters}, volume = {346}, number = {1}, pages = {148-157}, pmid = {24384092}, issn = {1872-7980}, support = {R01 DK061005/DK/NIDDK NIH HHS/United States ; Z01 DK061005//Intramural NIH HHS/United States ; }, mesh = {Base Sequence ; Blotting, Western ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Humans ; Molecular Sequence Data ; Protein Isoforms ; Reverse Transcriptase Polymerase Chain Reaction ; STAT5 Transcription Factor/*genetics/metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transfection ; Tumor Suppressor Proteins/*genetics/metabolism ; Up-Regulation ; }, abstract = {We have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1-2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma.}, } @article {pmid24380557, year = {2013}, author = {Rovera, F and Chiappa, C and Coglitore, A and Baratelli, GM and Fachinetti, A and Marelli, M and Frattini, F and Lavazza, M and Bascialla, L and Rausei, S and Boni, L and Corben, AD and Dionigi, G and Dionigi, R}, title = {Management of breast cancer during pregnancy.}, journal = {International journal of surgery (London, England)}, volume = {11 Suppl 1}, number = {}, pages = {S64-8}, doi = {10.1016/S1743-9191(13)60020-5}, pmid = {24380557}, issn = {1743-9159}, mesh = {Adult ; Breast Feeding ; Breast Neoplasms/*diagnosis/pathology/*therapy ; Delivery, Obstetric ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/pathology/*therapy ; Retrospective Studies ; }, abstract = {INTRODUCTION: Pregnancy-associated breast cancer (PABC) is one of the most common malignancies during pregnancy. Since maternal age at the time of pregnancy is increasing, PABC rate is expected to increase. Diagnostic delays are common.

METHODS: Retrospective observational study analysing twelve pregnant patients with breast cancer who underwent surgical treatment during the period of February 2006 to June 2013 at the Department of Surgery I, University of Insubria Varese.

RESULTS: The median age of pregnant patients was 34 y (range 28-44 y). Three patients were affected by BRCA1 mutation. In six patients diagnosis was made during gestation, in the other six patients breast cancer was discovered during breastfeeding. Ten patients underwent breast-conserving surgery. Sentinel lymph node biopsy was performed in six patients; in one of them it was positive so axillary dissection was simultaneuosly performed. Six patients underwent axillary dissection ab initio. In all cases the histological type was invasive ductal carcinoma; grade 3 in ten patients and grade 2 in two patients. Eleven of twelve patients received adjuvant chemotherapy, one patient both adjuvant and neoadjuvant. In three cases also radiation therapy was performed after delivery. In all cases healthy babies were born. Nine of twelve patients are still alive and disease free, after a median follow-up of 20 months (range 3-52 months). Three patients died from systemic progression of the disease.

CONCLUSION: There are no significant series of patients in worldwide literature to develop standard protocols. Pregnant women must be followed by a multidisciplinary team.}, } @article {pmid25960935, year = {2014}, author = {Vujanovic, L and Shi, J and Kirkwood, JM and Storkus, WJ and Butterfield, LH}, title = {Molecular mimicry of MAGE-A6 and Mycoplasma penetrans HF-2 epitopes in the induction of antitumor CD8[+] T-cell responses.}, journal = {Oncoimmunology}, volume = {3}, number = {8}, pages = {e954501}, pmid = {25960935}, issn = {2162-4011}, support = {R01 CA169118/CA/NCI NIH HHS/United States ; }, abstract = {A promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4[+] and CD8[+] T-cells. Previously, we reported that a MAGE-A6-derived peptide (MAGE-A6172-187) and its highly-immunogenic and cross-reactive homolog derived from Mycoplasma penetrans HF-2 permease (HF-2216-229) are promiscuously presented by multiple HLA-DR alleles to responder CD4[+] T-cells obtained from healthy donors and melanoma patients. Here, we investigated whether these same peptides could concomitantly stimulate cross-reactive MAGE-A6-specific CD8[+] T-cell responses in vitro using cells isolated from HLA-A*0201 (HLA-A2)[+] healthy individuals and patients with melanoma. We now show that MAGE-A6172-187 and, even more so, HF-2216-229, induce memory CD8[+] T cells that recognize HLA-A2[+] MAGE-A6[+] tumor target cells. The immunogenicity of these peptides was at least partially attributed to their embedded MAGE-A6176-185 and HF-2220-229 "homologous" sequences. The functional avidity of HF-2216-229 peptide-primed CD8[+] T cells for the MAGE-A6172-187 peptide was more than 100-fold greater than that of CD8[+] T cells primed with the corresponding MAGE-A6 peptide. Additionally, these 2 peptides were recognized in interferon γ (IFNγ) and granzyme B ELISPOT assays by CD8[+] T-cell clones displaying variable T-cell receptor (TCR) Vβ usage. These data suggest that the immune cross-reactivity of the MAGE-A6172-187 and HF-2216-229 peptides extends to CD8[+] T cells, at least in HLA-A2[+] donors, and supports the potential translational utility of these epitopes in clinical vaccine formulations and for immunomonitoring of cancer patients.}, } @article {pmid24377578, year = {2014}, author = {Seifi-Alan, M and Shamsi, R and Ghafouri-Fard, S and Mirfakhraie, R and Zare-Abdollahi, D and Movafagh, A and Modarressi, MH and Kazemi, G and Geranpayeh, L and Najafi-Ashtiani, M}, title = {Expression analysis of two cancer-testis genes, FBXO39 and TDRD4, in breast cancer tissues and cell lines.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {11}, pages = {6625-6629}, doi = {10.7314/apjcp.2013.14.11.6625}, pmid = {24377578}, issn = {2476-762X}, mesh = {Antigens, Neoplasm/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; F-Box Proteins/*genetics/metabolism ; Female ; Fibroadenoma/*genetics/metabolism/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleoproteins/*genetics/metabolism ; Tumor Cells, Cultured ; }, abstract = {Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.}, } @article {pmid24377562, year = {2014}, author = {Alipour, S and Omranipour, R and Jahanzad, I and Bagheri, K}, title = {Very young breast cancer in a referral center in Tehran, Iran; review of 55 cases aged 25 or less throughout 33 years.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {11}, pages = {6529-6532}, doi = {10.7314/apjcp.2013.14.11.6529}, pmid = {24377562}, issn = {2476-762X}, mesh = {Adult ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Female ; Humans ; Incidence ; Iran/epidemiology ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; *Referral and Consultation ; }, abstract = {BACKGROUND: Breast cancer is mostly the disease of postmenopausal women but very young affected women are seen more than occasionally in developing countries. We reviewed our cases of very young breast cancer in order to help in better understanding of such cases.

MATERIALS AND METHODS: The records of patients 25 years of age or less who had been admitted for breast cancer surgery in the Cancer Institute of Tehran from 1979 to 2012 were reviewed and relevant data were extracted.

RESULTS: From 5,265 cases of breast cancer, 62 patients had 25 years of age or less. There were 55 cases of breast adenocarcinoma, all female. More than 78% of the patients had presented with a palpable mass, the family history was positive in 2% of cases, and about 94% of the histologies were invasive ductal carcinoma. Gestational breast cancer constituted 10% of the cancers; another 10%were bilateral. The median size of the tumors was 5.72 centimeters, 63.2% of them had axillary lymphatic involvement, and more than half were negative for hormone receptors.

CONCLUSIONS: Our study shows an incidence of 1.17% for very young breast cancer and a 10% rate of bilaterality which probably warrants special guidelines for contralateral screening. Cancer stage and features were poor in comparison with breast cancer in all ages.}, } @article {pmid24377508, year = {2013}, author = {Hu, Q and Chen, WX and Zhong, SL and Li, J and Luo, Z and Tang, JH and Zhao, JH}, title = {Current progress in the treatment of metaplastic breast carcinoma.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {11}, pages = {6221-6225}, doi = {10.7314/apjcp.2013.14.11.6221}, pmid = {24377508}, issn = {2476-762X}, mesh = {Breast Neoplasms/*drug therapy/*pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Metaplasia/*pathology ; Prognosis ; }, abstract = {Metaplastic breast cancer (MBC) is a rare type of breast carcinoma, characterized by various combinations of mesenchymal, adenocarcinoma and other epithelial components. MBC often manifests as a large mass, with low axillary lymph node involvement and poor prognosis. Knowledge and treatment patterns about MBC demographics, presentation and tumor characteristics are very limited. In clinical practice, MBC is usually treated based on the guidelines developed for infiltrating ductal carcinoma (IDC). The ideal treatment paradigm for MBC is unknown due to its low incidence and pathological variability, so potential predictors of treatment efficacy need to be explored. This review summarizes the current models and strategies for MBC according to the published literature.}, } @article {pmid24376257, year = {2014}, author = {Toyonaga, Y and Yamazaki, K and Yamada, M and Koyasu, T and Koyama, Y and Ishida, Y}, title = {Brush cytology of acinar cell carcinoma of the pancreas with intraductal growth: a case report.}, journal = {Diagnostic cytopathology}, volume = {42}, number = {4}, pages = {321-324}, doi = {10.1002/dc.23087}, pmid = {24376257}, issn = {1097-0339}, mesh = {Aged ; Carcinoma, Acinar Cell/*diagnosis/diagnostic imaging/*pathology ; Carcinoma, Pancreatic Ductal/*diagnosis/diagnostic imaging/*pathology ; Cell Nucleus/pathology ; Cell Proliferation ; Cytodiagnosis/*methods ; Humans ; Male ; Pancreatic Neoplasms/*diagnosis/diagnostic imaging/*pathology ; Tomography, X-Ray Computed ; }, abstract = {We describe a rare case of pancreatic acinar cell carcinoma (ACC) with intraductal growth in a 77-year-old man, which was diagnosed by endoscopic brush cytology. Preoperative imaging revealed an ill-defined mass involving the main pancreatic duct of the body, which was suspected to be an invasive ductal carcinoma. Endoscopic brush cytology showed several thick, small to large clusters of tumor cells. However, a loosely cohesive or individual cell arrangement was more prominent. Singly dispersed naked nuclei, occasionally with crush artifact, were frequently observed. The nuclear contour was smooth and chromatin was finely clumped. The cytoplasm contained many coarse D-PAS-positive granules. Histologically, the tumor expansively invaded to parenchyma and expanded to fill the pancreatic ducts. Ultrastructurally, the tumor cells were less cohesive with scarce tight junctions, and their cytoplasm contained numerous zymogen granules and filamentous inclusions. Although ACCs usually show expansive growth, the incidence of intraductal extension may be higher than previously considered. A few of the characteristic cytomorphological features described here may be useful for differential diagnosis of this tumor from malignant epithelioid neoplasms involving the large pancreatic ducts.}, } @article {pmid24375061, year = {2013}, author = {Faghih, Z and Rezaeifard, S and Safaei, A and Ghaderi, A and Erfani, N}, title = {IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression.}, journal = {Iranian journal of immunology : IJI}, volume = {10}, number = {4}, pages = {193-204}, pmid = {24375061}, issn = {1735-367X}, mesh = {Adult ; Breast Neoplasms/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Carcinogenesis ; Carcinoma/*immunology ; Cell Separation ; Cells, Cultured ; Disease Progression ; Down-Regulation ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Interferon-gamma/genetics/metabolism ; Interleukin-17/metabolism ; Interleukin-4/metabolism ; Lymph Nodes/*pathology ; Lymphatic Metastasis/immunology ; Middle Aged ; T-Lymphocyte Subsets/*immunology ; }, abstract = {BACKGROUND: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile.

OBJECTIVE: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer.

METHODS: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status.

RESULTS: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively).

CONCLUSION: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.}, } @article {pmid24373403, year = {2013}, author = {Zhou, SJ and Guo, H}, title = {[Ki-67 expression and significance of different molecular subtypes of breast invasive ductal carcinoma].}, journal = {Zhonghua yi xue za zhi}, volume = {93}, number = {36}, pages = {2895-2897}, pmid = {24373403}, issn = {0376-2491}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Ki-67 Antigen/genetics/*metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {OBJECTIVE: To analyze Ki-67 expression and explore its significance in different molecular subtypes of breast invasive ductal carcinoma (IDC).

METHODS: The expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki-67 were detected in 126 cases of IDC by immunohistochemical staining. Then the molecular subtype of each case of IDC was determined.Statistical analysis was performed to determine the relationship between Ki-67 expression and the molecular subtypes with clinicopathological features of IDC.

RESULTS: There was no statistically significant difference of Ki-67 expression in age and tumor size (P > 0.05).However, significant difference existed in histological grading and lymph node metastasis (P < 0.05). The expression level of Ki-67 was negatively correlated with ER expression (r = -0.273, P = 0.002) and PR expression (r = -0.242, P = 0.007) and positively with HER-2 expression (r = 0.245, P = 0.006) . A low expression of Ki-67 was in LumianlA subtype (17/17) and high expression in other molecular subtypes. Moreover, the rate of high expression (Ki-67 LI>50%) in each subtype progressively increased with the degree of molecular typing and Ki-67 expression in different molecular subtypes showed significant difference (P < 0.05).

CONCLUSIONS: The expression level of Ki-67 is correlated with histological grading and molecular type of IDC. High expression of Ki-67 carries poor prognosis. Thus it is necessary to perform a variety of routine clinicopathological examinations, such as Ki-67, ER, PR and HER-2.}, } @article {pmid24373193, year = {2013}, author = {Choi, EJ and Yun, JA and Jeon, EK and Won, HS and Ko, YH and Kim, SY}, title = {Prognostic significance of RSPO1, WNT1, P16, WT1, and SDC1 expressions in invasive ductal carcinoma of the breast.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {314}, pmid = {24373193}, issn = {1477-7819}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Neoplasm Staging ; Prognosis ; Survival Rate ; Syndecan-1/*metabolism ; Thrombospondins/*metabolism ; WT1 Proteins/*metabolism ; Wnt1 Protein/*metabolism ; }, abstract = {BACKGROUND: To better understand the mechanisms of the SDC1 expression in invasive ductal carcinoma, we studied the correlations between SDC1 expression and related gene expressions (RSPO1, WNT1, WT1, and P16).

METHODS: Using 100 cases of invasive ductal carcinoma tissue, we screened expressions of RSPO1, WNT1, WT1, P16, and SDC1 using immunohistochemistry. We analyzed the association between the immunoreactivities and clinicopathological parameters.

RESULTS: WT1 expression was associated with tumor grade. RSPO1 expression was associated with progesterone receptor expression. Expressions of RSPO1, WT1, and P16 were significantly associated with disease-free survival. RSPO1 and P16 showed statistically significant hazard ratios. SDC1 ectodomain expression was significantly associated only with P16 expression. Immunoreactivity of SDC1 cytoplasmic domain was associated with WT1 and WNT1. However, WNT1 expression failed to show a significant association with disease-free survival.

CONCLUSIONS: RSPO1 and P16 immunoreactivity was found to be an independent prognostic indicator in invasive ductal cancer. Cytoplasmic expression of SDC1 is positively correlated with tumor-prone proteins (WT1 and WNT1) and membranous expression of SDC1 is positively correlated with the tumor suppressor (P16).}, } @article {pmid24371992, year = {2013}, author = {Sumiyoshi, N and Fukuyama, R and Senda, M and Yokoi, T and Nagasaka, T}, title = {[On the correlation between histological and cytological diagnosis, and the intrinsic 5 subtypes].}, journal = {Rinsho byori. The Japanese journal of clinical pathology}, volume = {61}, number = {10}, pages = {887-892}, pmid = {24371992}, issn = {0047-1860}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Japan ; Ki-67 Antigen/analysis/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis/metabolism ; }, abstract = {Japanese General Rules presented by the Japanese Breast Cancer Society have been long time applied in Japan. This classification uniquely adds subtypes into the group of invasive ductal carcinomas (IDC) and reported to be correlated to patients' clinical course. The latest St. Gallen consensus meeting reported the use of 5 molecules, and introduced alternative definition in the breast cancer classification. The purpose of this study is to relate the Japanese subgrouping of IDC with the 5 subtypes and to investigate whether these classifications could predict early and late recurrence and whether cytological diagnosis is influenced by the tumor phenotypes. Analyzing 127 cases, we observed that the Ki-67 labeling index (LI) of the 5 subtypes, luminal A, luminal B-Her2--/- Her2+, Her2-subtype and basal-like, is increased in this order. Though the Japanese histological groups, papillotubular, solid-tubular and scirrhous, included more or less those subtypes, the luminal types were more represented in papillotubular and scirrhous subtypes, and the solid-tubular type in non luminal subtypes. The Ki-67 LI 14% served as a cutoff for differentiating invasive from non-invasive ductal carcinomas. Breast cancers recur within 5 years after the clinical onset when the Ki-67 LI exceeded 14%. These data suggest that, (1) the intrinsic subtyping is an accurate modality in diagnosing breast cancers, (2) it can predict the recurrence duration, (3) the solid-tubular type of the Japanese classification is likely an aggressive form among breast cancers, and (4) the cytological diagnosis is presently a powerful tool in determining malignancy.}, } @article {pmid24371219, year = {2015}, author = {Alfonso, YN and Bishai, D and Bua, J and Mutebi, A and Mayora, C and Ekirapa-Kiracho, E}, title = {Cost-effectiveness analysis of a voucher scheme combined with obstetrical quality improvements: quasi experimental results from Uganda.}, journal = {Health policy and planning}, volume = {30}, number = {1}, pages = {88-99}, doi = {10.1093/heapol/czt100}, pmid = {24371219}, issn = {1460-2237}, mesh = {Cost-Benefit Analysis ; Female ; Health Care Costs ; *Healthcare Financing ; Humans ; Maternal Mortality ; Obstetrics/*economics/organization & administration/standards ; Pregnancy ; Quality Improvement/economics/*organization & administration ; Reimbursement Mechanisms/economics/organization & administration ; Uganda ; }, abstract = {The maternal mortality ratio (MMR) in Uganda has declined significantly during the last 20 years, but Uganda is not on track to reach the millennium development goal of reducing MMR by 75% by 2015. More evidence on the cost-effectiveness of supply- and demand-side financing programs to reduce maternal mortality could inform future strategies. This study analyses the cost-effectiveness of a voucher scheme (VS) combined with health system strengthening in rural Uganda against the status quo. The VS, implemented in 2010, provided vouchers for delivery services at public and private health facilities (HF), as well as round-trip transportation provided by private sector workers (bicycles or motorcycles generally). The VS was part of a quasi-experimental non-randomized control trial. Improvements in institutional delivery coverage (IDC) rates can be estimated using a difference-in-difference impact evaluation method and the number of maternal lives saved is modelled using the evidence-based Lives Saved Tool. Costs were estimated from primary and secondary data. Results show that the demand for births at HFs enrolled in the VS increased by 52.3 percentage points. Out of this value, conservative estimates indicate that at least 9.4 percentage points are new HF users. This 9.4% bump in IDC implies 20 deaths averted, which is equivalent to 1356 disability-adjusted-life years (DALYs) averted. Cost-effectiveness analysis comparing the status quo and VS's most conservative effectiveness estimates shows that the VS had an incremental cost-effectiveness ratio per DALY averted of US$302 and per death averted of US$20 756. Although there are limitations in the data measures, a favourable cost-effectiveness ratio persists even under extreme assumptions. Demand-side vouchers combined with supply-side financing programs can increase attended deliveries and reduce maternal mortality at a cost that is acceptable.}, } @article {pmid24371107, year = {2014}, author = {Grajo, JR and Barr, RG}, title = {Strain elastography for prediction of breast cancer tumor grades.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {33}, number = {1}, pages = {129-134}, doi = {10.7863/ultra.33.1.129}, pmid = {24371107}, issn = {1550-9613}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnostic imaging/*pathology ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Neoplasm Grading ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography, Mammary/*methods ; }, abstract = {OBJECTIVES: The purpose of this study was to determine whether the elasticity imaging/B-mode ratio on strain elastography can predict breast cancer tumor grades.

METHODS: A retrospective review of patients with breast lesions who underwent strain elastography and had a diagnosis of breast cancer by image-guided or surgical biopsy was performed. The axis of the maximum elastographic dimension was compared to the B-mode dimension to form an elasticity imaging/B-mode ratio. Lesions were categorized according to their pathologic type, including atypical ductal hyperplasia (ADH), mucinous or colloid cancer, ductal carcinoma in situ (DCIS), grade I invasive ductal carcinoma (IDC), grade II IDC, grade III IDC, invasive lobular carcinoma (ILC), and lymphoma. The mean elasticity imaging/B-mode ratio of each tumor type was calculated. The elasticity imaging/B-mode ratio of the tumor was compared to the tumor type by Kruskal-Wallis and Tukey-Kramer tests (lymphoma and ADH excluded because of small numbers).

RESULTS: Tumor grades included lymphoma (n = 3), ADH (n = 2), mucinous cancer (n = 11), DCIS (n = 19), IDC (grades I-III; n = 200), and ILC (n = 31). The mean elasticity imaging/B-mode ratio varied with increasing tumor grade. Tumor grades could not have been selected at random from one population (P < .0001, χ(2) test). Invasive lobular carcinoma and grade III IDC were statistically different from mucinous or colloid cancer, DCIS, and grade I and II IDC.

CONCLUSIONS: The elasticity imaging/B-mode ratio on strain elastography is related to the tumor grade.}, } @article {pmid24369200, year = {2013}, author = {Mohapatra, M and Satyanarayana, S}, title = {Evaluation of clinico: pathologic findings of breast carcinoma in a general hospital in Southern India.}, journal = {Indian journal of cancer}, volume = {50}, number = {4}, pages = {297-301}, doi = {10.4103/0019-509X.123594}, pmid = {24369200}, issn = {1998-4774}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Female ; Humans ; India/epidemiology ; Male ; Middle Aged ; *Prognosis ; }, abstract = {BACKGROUND AND OBJECTIVES: Breast cancer is the second most common cancer in the Indian female population. As per our hospital data, breast cancer is also found to be the second leading malignancy in women. Hence, we undertook this study to evaluate the clinical profile, histopathologic types, grade, stage and the prognosis of the disease in our patients. Majority of our patients are from rural areas.

MATERIALS AND METHODS: This study was undertaken over a period of three years comprising of 178 patients who underwent modified radical mastectomy following preliminary diagnosis of carcinoma on fine needle aspiration cytology or histopathological examination of the lumpectomy or trucut biopsy specimens. Clinico-pathological evaluation was done in all of these cases following standard protocols.

RESULT: The study comprised of 175 female patients and 3 male patients in the age range of 28 to 76 years. Majority (111/62.3%) of the cases were within the age range of 31-50 years of age with mean age of 48.7 years. Two females had bilateral breast cancer and one female had synchronous papillary serous cystadenocarcinoma of the ovary. Invasive ductal carcinoma no special type was the most common histopathologic pattern, and was seen in 172 (95.5%) cases. Most tumors were Scarff Bloom Richardson grade II and American Joint Committee on Cancer pathologic stage II. Prognostically, majority of tumors (49.5%) was assessed as 'good' as per the Nottingham prognostic index score.

CONCLUSIONS: This study gave an insight to the clinico-pathological profile of breast cancer in our area. Long term study with follow up of the patient is needed for better understanding of the case.}, } @article {pmid24368622, year = {2014}, author = {Moore, T and Rodriguez, A and Bakken, JS}, title = {Fecal microbiota transplantation: a practical update for the infectious disease specialist.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {58}, number = {4}, pages = {541-545}, doi = {10.1093/cid/cit950}, pmid = {24368622}, issn = {1537-6591}, mesh = {Biological Therapy/*methods ; Drugs, Investigational/*therapeutic use ; Feces/*microbiology ; Gastrointestinal Diseases/*therapy ; Humans ; *Investigational New Drug Application ; United States ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be a superior therapeutic modality for the treatment of recurrent Clostridium difficile infection (RCDI). Recently the US Food and Drug Administration (FDA) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. Consequently, the FDA determined that prescribers of FMT must possess an approved investigational new drug (IND) permit to administer FMT for the purpose of conducting research or treating any gastrointestinal condition other than RCDI. Although an IND is not required for use of FMT to treat RCDI, an IND is strongly encouraged and may ultimately be required. This article provides step-by-step guidance to infectious disease specialists on how to navigate the regulatory requirements and successfully obtain an IND before they can begin to use FMT as part of their clinical practice.}, } @article {pmid24366300, year = {2014}, author = {Airley, RE and McHugh, P and Evans, AR and Harris, B and Winchester, L and Buffa, FM and Al-Tameemi, W and Leek, R and Harris, AL}, title = {Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression.}, journal = {British journal of cancer}, volume = {110}, number = {3}, pages = {715-723}, pmid = {24366300}, issn = {1532-1827}, mesh = {Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*biosynthesis/genetics ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Glucose Transporter Type 1/biosynthesis/genetics ; Humans ; Hypoxia/*genetics/pathology ; Immunohistochemistry ; MCF-7 Cells ; Prognosis ; }, abstract = {BACKGROUND: The lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) may play a key role in malignant progression of breast cancer by allowing metabolic adaptations to take place in response to changes in oxygenation.

METHODS: Immunohistochemical analysis of ChREBP was carried out in human breast tumour tissue microarrays representative of malignant progression from normal breast through to metastatic cancer. The ChREBP protein and mRNA expressions were then analysed in a series of breast cancers for correlative analysis with common and breast-specific hypoxia signatures, and survival.

RESULTS: In invasive ductal carcinoma, ChREBP correlated significantly with mean 'downregulated' hypoxia scores (r=0.3, P<0.015, n=67) and in two distinct breast progression arrays, ChREBP protein also increased with malignant progression (P<0.001). However, bioinformatic analysis of a large data set (2136 cases) revealed an apparent reversal in the relationship between ChREBP mRNA level and clinical outcome - not only being significantly correlated with increased survival (log rank P<0.001), but also downregulated in malignant tissue compared with adjacent normal tissue.

CONCLUSION: The ChREBP expression may be reflective of an aerobic metabolic phenotype that may conflict with hypoxia-induced signalling but provide a mechanism for growth at the oxygenated edge of the tumours.}, } @article {pmid24363939, year = {2013}, author = {da Silva, GB and Silva, TG and Duarte, RA and Neto, NL and Carrara, HH and Donadi, EA and Gonçalves, MA and Soares, EG and Soares, CP}, title = {Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer.}, journal = {International journal of breast cancer}, volume = {2013}, number = {}, pages = {250435}, pmid = {24363939}, issn = {2090-3170}, abstract = {Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC) of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated) and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6%) out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9%) showed high expression of HLA-E. A large number (41, 78.8%) of the biopsies showed low expression of HLA-Ia, while 45 (86.5%) showed high expression of HLA-DQ and 36 (69.2%) underexpressed HLA-DR. Moreover, 24 (41.2%) of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2%) had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness.}, } @article {pmid24356765, year = {2013}, author = {Alipour, S and Seifollahi, A and Anbiaee, R}, title = {Lactating breast abscess: a rare presentation of adenosquamous breast carcinoma.}, journal = {Singapore medical journal}, volume = {54}, number = {12}, pages = {e247-9}, doi = {10.11622/smedj.2013251}, pmid = {24356765}, issn = {2737-5935}, mesh = {Adult ; Breast Neoplasms/*diagnosis/drug therapy/radiotherapy/surgery ; Carcinoma, Adenosquamous/*diagnosis/drug therapy/radiotherapy/surgery ; Carcinoma, Ductal, Breast/diagnosis/drug therapy/radiotherapy/surgery ; Female ; Humans ; Inflammation ; *Lactation ; Risk Factors ; Treatment Outcome ; }, abstract = {We report the case of a 33-year-old lactating woman who presented with a 10-cm breast abscess. Biopsy of the abscess wall revealed a poorly differentiated invasive ductal carcinoma. The patient had no family history of breast cancer or other risk factors for breast cancer. The disease was considered to be a large noninflammatory invasive breast cancer, for which the patient received neoadjuvant chemotherapy, breast-conserving surgery using axillary dissection (the patient did not consent to a mastectomy), and postoperative radiotherapy. Final histologic examination revealed a 4-cm, triple negative, high-grade adenosquamous carcinoma. At follow-up four years after surgery, the patient was doing well with no signs of recurrence. Adenosquamous carcinoma is an extremely rare disease that mainly presents in low-grade forms. High-grade forms are aggressive and frequently present with axillary involvement. To the best of our knowledge, there has been no report of adenosquamous carcinoma presenting as a breast abscess in the literature. The case we report highlights that, although rare, cancer should be considered in lactating breast abscesses.}, } @article {pmid24354864, year = {2013}, author = {Shindo, K and Aishima, S and Ohuchida, K and Fujiwara, K and Fujino, M and Mizuuchi, Y and Hattori, M and Mizumoto, K and Tanaka, M and Oda, Y}, title = {Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.}, journal = {Molecular cancer}, volume = {12}, number = {1}, pages = {168}, pmid = {24354864}, issn = {1476-4598}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/pathology ; Coculture Techniques ; Disease Progression ; Female ; Fibroblasts/*metabolism ; Gene Expression ; Humans ; Kaplan-Meier Estimate ; Male ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*metabolism/mortality/pathology ; Proportional Hazards Models ; RNA, Messenger/genetics/metabolism ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.

METHODS: Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN- CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs.

RESULTS: PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461), vascular invasion (P = 0.0101), tumor size ≥ 3 cm (P = 0.0038), histological grade (P = 0.0344), Union for International Cancer Control classification T stage (P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor.

CONCLUSIONS: PDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.}, } @article {pmid24354443, year = {2013}, author = {Ogundiran, TO and Ayandipo, OO and Ademola, AF and Adebamowo, CA}, title = {Mastectomy for management of breast cancer in Ibadan, Nigeria.}, journal = {BMC surgery}, volume = {13}, number = {}, pages = {59}, pmid = {24354443}, issn = {1471-2482}, support = {D43 TW009106/TW/FIC NIH HHS/United States ; U54 HG006947/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*surgery ; Breast Neoplasms, Male/surgery ; Carcinoma, Ductal, Breast/*surgery ; Developing Countries ; Female ; Follow-Up Studies ; Humans ; Length of Stay/statistics & numerical data ; Male ; *Mastectomy, Modified Radical/statistics & numerical data ; Middle Aged ; Nigeria ; Postoperative Complications/epidemiology ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Modified radical mastectomy remains the standard therapeutic surgical operation for breast cancer in most parts of the world. This retrospective study reviews mastectomy for management of breast cancer in a surgical oncology division over a ten year period.

METHODS: We reviewed the case records of consecutive breast cancer patients who underwent mastectomy at the Surgical Oncology Division, University College Hospital (UCH) Ibadan between November 1999 and October 2009.

RESULTS: Of the 1226 newly diagnosed breast cancer patients over the study period, 431 (35.2%) patients underwent mastectomy making an average of 43 mastectomies per year. Most patients were young women, premenopausal, had invasive ductal carcinoma and underwent modified radical mastectomy as the definitive surgical treatment. Prior to mastectomy, locally advanced tumors were down staged in about half of the patients that received neo-adjuvant combination chemotherapy. Surgical complication rate was low. The most frequent operative complication was seroma collection in six percent of patients. The average hospital stay was ten days and most patients were followed up at the surgical outpatients department for about two years post-surgery.

CONCLUSIONS: There was low rate of mastectomy in this cohort which could partly be attributable to late presentation of many patients with inoperable local or metastatic tumors necessitating only palliative or terminal care. Tumor down-staging with neo-adjuvant chemotherapy enhanced surgical loco-regional tumor control in some patients. The overall morbidity and the rates of postoperative events were minimal. Long-term post-operative out-patients follow-up was not achieved as many patients were lost to follow up after two years of mastectomy.}, } @article {pmid24353241, year = {2015}, author = {Park, SH and Choi, HY and Hahn, SY}, title = {Correlations between apparent diffusion coefficient values of invasive ductal carcinoma and pathologic factors on diffusion-weighted MRI at 3.0 Tesla.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {41}, number = {1}, pages = {175-182}, doi = {10.1002/jmri.24519}, pmid = {24353241}, issn = {1522-2586}, mesh = {Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Middle Aged ; Retrospective Studies ; Tumor Burden ; }, abstract = {PURPOSE: To investigate correlations between apparent diffusion coefficient (ADC) values of invasive ductal carcinoma (IDC) and pathologic factors on diffusion-weighted MRI. We measured the ADC values of IDC of the breast and analyzed correlations between ADC values and factors such as tumor size, axillary lymph node status, histologic grade, estrogen receptor, progesterone receptor, and human epithelial growth factor 2 (HER2) using diffusion-weighted MRI at 3.0 Tesla (T).

MATERIALS AND METHODS: We examined 110 patients with pathologically confirmed IDC using diffusion-weighted MRI at 3.0T. The ADC values of breast cancer were calculated using two b factors (0 and 1000 s/mm(2)). The relationship between ADC values and tumor size, histologic grade, axillary lymph node status, hormonal receptors, and HER2 were analyzed.

RESULTS: The mean ADC value of IDC (n = 110) was 0.88 ± 0.15 × 10(-2) mm(2)/s. Tumors were subgrouped according to size (<2 cm, 2-5 cm, and ≥5 cm). Multiple comparisons within subgroups according to size showed that the ADC values for the three tumor size groups were significantly different (correlation coefficient = -0.007). The mean apparent diffusion coefficient of HER2-positive IDC was significantly higher than that of HER2-negative invasive ductal carcinoma (correlation coefficient = 0.218).

CONCLUSION: ADC values of IDC were significantly correlated with tumor size and HER2 status.}, } @article {pmid24349253, year = {2013}, author = {Wang, LW and Qu, AP and Yuan, JP and Chen, C and Sun, SR and Hu, MB and Liu, J and Li, Y}, title = {Computer-based image studies on tumor nests mathematical features of breast cancer and their clinical prognostic value.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82314}, pmid = {24349253}, issn = {1932-6203}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Disease-Free Survival ; Female ; Humans ; *Image Processing, Computer-Assisted ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local/pathology ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; ROC Curve ; }, abstract = {BACKGROUND: The expending and invasive features of tumor nests could reflect the malignant biological behaviors of breast invasive ductal carcinoma. Useful information on cancer invasiveness hidden within tumor nests could be extracted and analyzed by computer image processing and big data analysis.

METHODS: Tissue microarrays from invasive ductal carcinoma (n = 202) were first stained with cytokeratin by immunohistochemical method to clearly demarcate the tumor nests. Then an expert-aided computer analysis system was developed to study the mathematical and geometrical features of the tumor nests. Computer recognition system and imaging analysis software extracted tumor nests information, and mathematical features of tumor nests were calculated. The relationship between tumor nests mathematical parameters and patients' 5-year disease free survival was studied.

RESULTS: There were 8 mathematical parameters extracted by expert-aided computer analysis system. Three mathematical parameters (number, circularity and total perimeter) with area under curve >0.5 and 4 mathematical parameters (average area, average perimeter, total area/total perimeter, average (area/perimeter)) with area under curve <0.5 in ROC analysis were combined into integrated parameter 1 and integrated parameter 2, respectively. Multivariate analysis showed that integrated parameter 1 (P = 0.040) was independent prognostic factor of patients' 5-year disease free survival. The hazard risk ratio of integrated parameter 1 was 1.454 (HR 95% CI [1.017-2.078]), higher than that of N stage (HR 1.396, 95% CI [1.125-1.733]) and hormone receptor status (HR 0.575, 95% CI [0.353-0.936]), but lower than that of histological grading (HR 3.370, 95% CI [1.125-5.364]) and T stage (HR 1.610, 95% CI [1.026 -2.527]).

CONCLUSIONS: This study indicated integrated parameter 1 of mathematical features (number, circularity and total perimeter) of tumor nests could be a useful parameter to predict the prognosis of early stage breast invasive ductal carcinoma.}, } @article {pmid24348830, year = {2014}, author = {Suciu, C and Muresan, A and Cornea, R and Suciu, O and Dema, A and Raica, M}, title = {Semi-automated evaluation of Ki-67 index in invasive ductal carcinoma of the breast.}, journal = {Oncology letters}, volume = {7}, number = {1}, pages = {107-114}, pmid = {24348830}, issn = {1792-1074}, abstract = {A significant factor that affects the value of the Ki-67 proliferation index (IK) is the interpretation and implementation approach. This method is based on visual or automated methods to count tumor nuclei labeled with Ki-67 antigen, and is prone to errors. Detection of Ki-67 is a useful tool in breast cancer and contributes to its molecular classification. The current study proposes a method for the quantification of Ki-67-positive tumor nuclei, which allows for the determination of the exact IK value that is required for tumor stratification based on the proliferation rate. The IK was assessed in 81 successive cases of diagnosed invasive ductal breast carcinoma using a semi-automated method that accurately identifies positive tumor cell nuclei. This method prevents the inclusion of other possible positive cells, including lymphoid, normal epithelia and hyperplastic. In small specimens with increased cell density, where the nucleus/cytoplasm ratio is markedly in favor of the nucleus and the distance between nuclei is small, the method allows precise quantification of the nuclei, even when the limits between nuclei are difficult to identify. In addition, images may be stored in a database, including the assessments, and easily accessed when required. We hypothesize that the semi-automated method for counting nuclei offers the most accurate method of assessing the IK and avoids counting errors that may occur through other methods.}, } @article {pmid24333009, year = {2014}, author = {Cuzick, J and Sestak, I and Forbes, JF and Dowsett, M and Knox, J and Cawthorn, S and Saunders, C and Roche, N and Mansel, RE and von Minckwitz, G and Bonanni, B and Palva, T and Howell, A and , }, title = {Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.}, journal = {Lancet (London, England)}, volume = {383}, number = {9922}, pages = {1041-1048}, doi = {10.1016/S0140-6736(13)62292-8}, pmid = {24333009}, issn = {1474-547X}, support = {5032/CRUK_/Cancer Research UK/United Kingdom ; BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; C569/A5032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adult ; Aged ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/*prevention & control ; Carcinoma, Ductal, Breast/*prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*prevention & control ; Carcinoma, Lobular/*prevention & control ; Double-Blind Method ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Nitriles/*therapeutic use ; Postmenopause ; Proportional Hazards Models ; Risk Factors ; Treatment Outcome ; Triazoles/*therapeutic use ; }, abstract = {BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.

FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836).

INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.

FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.}, } @article {pmid24331871, year = {2014}, author = {Arzouan, Y and Moses, E and Peled, A and Levit-Binnun, N}, title = {Impaired network stability in schizophrenia revealed by TMS perturbations.}, journal = {Schizophrenia research}, volume = {152}, number = {1}, pages = {322-324}, doi = {10.1016/j.schres.2013.11.017}, pmid = {24331871}, issn = {1573-2509}, mesh = {Brain/*physiopathology ; Electroencephalography/*methods ; Evoked Potentials/*physiology ; Female ; Humans ; Male ; Schizophrenia/*diagnosis/*physiopathology ; Transcranial Magnetic Stimulation/*methods ; }, } @article {pmid24331309, year = {2014}, author = {Babar, M and Madani, R and Thwaites, L and Jackson, PA and Devalia, HL and Chakravorty, A and Irvine, TE and Layer, GT and Kissin, MW}, title = {A differential intra-operative molecular biological test for the detection of sentinel lymph node metastases in breast carcinoma. An extended experience from the first U.K. centre routinely offering the service in clinical practice.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {40}, number = {3}, pages = {282-288}, doi = {10.1016/j.ejso.2013.10.030}, pmid = {24331309}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Chi-Square Distribution ; Cohort Studies ; Female ; Humans ; Lymph Node Excision/methods ; Lymph Nodes/pathology/surgery ; Middle Aged ; Monitoring, Intraoperative/*methods ; Neoplasm Invasiveness/pathology ; Neoplasm Micrometastasis/pathology ; Neoplasm Staging ; Nucleic Acid Amplification Techniques/*methods ; Oncology Service, Hospital ; Prognosis ; RNA, Messenger/analysis ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Sentinel Lymph Node Biopsy/*methods ; Survival Rate ; United Kingdom ; }, abstract = {INTRODUCTION: One-Step Nucleic acid Amplification (OSNA) is a molecular biological assay of cytokeratin-19 (a breast epithelial marker) mRNA. It can be employed intra-operatively for detection of lymph node metastases in breast carcinoma. Patients with positive sentinel nodes may proceed to axillary lymph node dissection (ALND) level I or higher dependent upon the OSNA quantitative result, during the same surgical procedure, avoiding a second operation and eliminating the technical difficulties possibly associated with delayed ALND.

AIMS: Our Breast Unit was the first in the UK to implement this novel technique in routine practice. This study reviews our first 44-month data following introduction of OSNA "live" on whole sentinel nodes following an extensive validation study (Snook et al.).(9) METHODS: Data was collected prospectively from the period of introduction 01/12/2008 to 30/08/2012. All patients eligible for sentinel node biopsy were offered OSNA and operations were performed by five consultant breast surgeons. On detection of macro-metastasis a level II/III and for a micro-metastasis a level I ALND was performed.

RESULTS: A total of 859 patients (1709 sentinel lymph nodes) were analysed. All except one were females. The majority underwent wide local excision (73.4%, n = 631) or mastectomy 25% (n = 215) and 1.6% (13) underwent SLN biopsy alone. IDC was seen in 79% (n = 680) of the patients and 53.5% (n = 460) had grade II tumours. One-third (30.8%, n = 265) had positive sentinel nodes and had further axillary surgery at the time of SLN biopsy. Of these, 47% (n = 125/265) had macro-metastases, 38% (n = 101/265) had micro-metastases and 14.7% (n = 39/265) had "positive but inhibited" results. Positive non-sentinel lymph nodes (NSLN) were seen in 35% (44/125) of those with macro-metastases; 17.8% (18/101) of the patients with micro-metastases and 10.2% (4/39) of the "positive but inhibited" group.

CONCLUSION: In our series over a third of our patients had positive lymph nodes detected with OSNA allowing them to proceed directly to axillary surgery at the same operation. This technique eliminates the need for a second operation in sentinel lymph node positive patients and avoids the anxiety waiting for histological results.}, } @article {pmid24324904, year = {2013}, author = {Sobinsky, JD and Willson, TD and Podbielski, FJ and Connolly, MM}, title = {Unusual metastatic patterns of invasive lobular carcinoma of the breast.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {986517}, pmid = {24324904}, issn = {2090-6706}, abstract = {Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3 cm sigmoid adenocarcinoma. The patient underwent a lower anterior resection. Pathology showed an ulcerated, invasive moderately differentiated adenocarcinoma extending into but not through the muscularis propria. However, six of seventeen paracolonic lymph nodes were positive for metastatic breast carcinoma (ER+/PR+), consistent with her lobular primary breast carcinoma; there was no evidence of metastatic colon cancer. This case highlights the unusual metastatic patterns of lobular carcinoma.}, } @article {pmid24324334, year = {2013}, author = {Andrade, CG and Cabral Filho, PE and Tenório, DP and Santos, BS and Beltrão, EI and Fontes, A and Carvalho, LB}, title = {Evaluation of glycophenotype in breast cancer by quantum dot-lectin histochemistry.}, journal = {International journal of nanomedicine}, volume = {8}, number = {}, pages = {4623-4629}, pmid = {24324334}, issn = {1178-2013}, mesh = {Breast/*chemistry ; Breast Neoplasms/*chemistry ; Concanavalin A/chemistry/*metabolism ; Female ; Glycoconjugates/*analysis/chemistry/metabolism ; Histocytochemistry/*methods ; Humans ; Microscopy, Fluorescence ; *Quantum Dots ; }, abstract = {Cell surface glycoconjugates play an important role in differentiation/dedifferentiation processes and lectins are employed to evaluate them by several methodologies. Fluorescent probes are considered a valuable tool because of their ability to provide a particular view, and are more detailed and sensitive in terms of cell structure and molecular content. The aim of this study was to evaluate and compare the expression and distribution of glycoconjugates in normal human breast tissue, and benign (fibroadenoma), and malignantly transformed (invasive ductal carcinoma) breast tissues. For this, we used mercaptosuccinic acid-coated Cadmium Telluride (CdTe) quantum dots (QDs) conjugated with concanavalin A (Con A) or Ulex europaeus agglutinin I (UEA I) lectins to detect α-D-glucose/mannose and L-fucose residues, respectively. The QD-lectin conjugates were evaluated by hemagglutination activity tests and carbohydrate inhibition assays, and were found to remain functional, keeping their fluorescent properties and carbohydrate recognition ability. Fluorescence images showed that different regions of breast tissue expressed particular types of carbohydrates. While the stroma was preferentially and intensely stained by QD-Con A, ductal cells were preferentially labeled by QD-UEA I. These results indicate that QD-lectin conjugates can be used as molecular probes and can help to elucidate the glycoconjugate profile in biological processes.}, } @article {pmid24321462, year = {2014}, author = {O'Malley, DP and Zuckerberg, L and Smith, LB and Barry, TS and Gunn, S and Tam, W and Orazi, A and Kim, YS and Weiss, LM}, title = {The genetics of interdigitating dendritic cell sarcoma share some changes with Langerhans cell histiocytosis in select cases.}, journal = {Annals of diagnostic pathology}, volume = {18}, number = {1}, pages = {18-20}, doi = {10.1016/j.anndiagpath.2013.10.003}, pmid = {24321462}, issn = {1532-8198}, mesh = {Comparative Genomic Hybridization ; Dendritic Cell Sarcoma, Interdigitating/*genetics/*pathology ; Histiocytosis, Langerhans-Cell/*genetics/*pathology ; Humans ; }, abstract = {Histiocytic disorders have been noted to have evidence of transdifferentiation; examples of cases with combinations of different lineages have been shown. In our index case, we identified interdigitating dendritic cell (IDC) differentiation in a case of Langerhans cell histiocytosis (LCH). Little is currently known about the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and compared them with our index case, as well as genetic abnormalities previously found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH with IDC differentiation were evaluated using aCGH. Array CGH results showed no abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of 4 cases of IDCS, genetic abnormalities were identified; 1 case had no identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p, 12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A number of LCH cases do not have detectable genetic abnormalities. In contrast, 3 of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore, 2 of these shared abnormalities, albeit of large genetic regions, with published abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS cases. However, the possibility of a relationship between IDCS and LCH cannot be entirely excluded by these results.}, } @article {pmid24316550, year = {2014}, author = {Son, CH and Bae, JH and Shin, DY and Lee, HR and Choi, YJ and Jo, WS and Ho Jung, M and Kang, CD and Yang, K and Park, YS}, title = {CTLA-4 blockade enhances antitumor immunity of intratumoral injection of immature dendritic cells into irradiated tumor in a mouse colon cancer model.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {37}, number = {1}, pages = {1-7}, doi = {10.1097/CJI.0000000000000007}, pmid = {24316550}, issn = {1537-4513}, mesh = {Animals ; Antibodies, Monoclonal/immunology/*pharmacology ; CTLA-4 Antigen/*antagonists & inhibitors/immunology ; Cell Line, Tumor ; Colonic Neoplasms/*immunology/mortality/radiotherapy/therapy ; Dendritic Cells/*immunology/*transplantation ; Disease Models, Animal ; Immunotherapy, Adoptive ; Interferon-gamma/biosynthesis ; Lymphocyte Activation/drug effects/immunology ; Male ; Mice ; T-Lymphocytes, Cytotoxic/immunology ; Th1 Cells/drug effects/immunology ; }, abstract = {Dendritic cells (DCs)-based cancer immunotherapy has been used various strategies to inhibit immune suppressive mechanisms. CD25 antibodies and cyclophosphamide are well-studied immunomodulators through inhibition of regulatory T cells (Treg) and a blockade the immune-checkpoint molecule, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was recently targeted for immunomodulation. We used anti-CTLA-4 antibody, which is known to induce effective antitumor immunity by facilitating tumor-specific T-cell activation and suppressing Treg cells, as useful immunomodulator to provide a potentiating effect in the intratumoral injection of immature DCs (iDCs) into the irradiated tumor (IR/iDC). Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh of mice. Then, iDCs were intratumorally injected into the irradiated tumor. Anti-CTLA-4 antibody (100 µg/mouse) was administered intraperitoneally to mice on the same day with every iDCs injection. The growth of distant tumors was inhibited by IR/iDC and this effect was significantly augmented by combination treatment of anti-CTLA-4 antibody. Furthermore, the survival rate of tumor-bearing mice improved more by the combination treatment of anti-CTLA-4 antibody and IR/iDC compared with other groups. It was related to the increased tumor-specific interferon-γ-secreting T cells and CTL activity. Therefore, our results demonstrated that immunomodulator such as anti-CTLA-4 antibody enhances antitumor immunity of intratumoral injection of iDCs into irradiated tumor and suggested a new strategy to get more clinical benefits for cancer treatment.}, } @article {pmid24309373, year = {2014}, author = {Thakur, C and Lu, Y and Sun, J and Yu, M and Chen, B and Chen, F}, title = {Increased expression of mdig predicts poorer survival of the breast cancer patients.}, journal = {Gene}, volume = {535}, number = {2}, pages = {218-224}, pmid = {24309373}, issn = {1879-0038}, support = {R01 ES017217/ES/NIEHS NIH HHS/United States ; R01 ES020137/ES/NIEHS NIH HHS/United States ; }, mesh = {Breast Neoplasms/*metabolism/*mortality/pathology ; Dioxygenases ; Female ; Gene Expression Regulation, Neoplastic ; Gene Order ; Histone Demethylases ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Nuclear Proteins/genetics/*metabolism ; Prognosis ; }, abstract = {Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races and Hispanic origin populations in the United States. In the present study, we reported that the survival time of the breast cancer patients is influenced by the expression level of mdig, a previously identified lung cancer-associated oncogene encoding a JmjC-domain protein. By checking the expression levels of mRNA and protein of mdig through both RT-PCR and immunohistochemistry in samples from 204 patients, we noticed that about 30% of breast cancer samples showed increased expression of mdig. Correlation of the mdig expression levels with the survival time of the breast cancer patients indicated a clear inverse relationship between mdig expression and patient survival, including poorer overall survival, distant metastasis free survival, relapse free survival, and post-progression survival. Taken together, these data suggest that an increased expression of mdig is an important prognostic factor for poorer survival time of the breast cancer patients.}, } @article {pmid24305978, year = {2014}, author = {Fortune-Greeley, AK and Wheeler, SB and Meyer, AM and Reeder-Hayes, KE and Biddle, AK and Muss, HB and Carpenter, WR}, title = {Preoperative breast MRI and surgical outcomes in elderly women with invasive ductal and lobular carcinoma: a population-based study.}, journal = {Breast cancer research and treatment}, volume = {143}, number = {1}, pages = {203-212}, pmid = {24305978}, issn = {1573-7217}, support = {P50 CA058223/CA/NCI NIH HHS/United States ; R25 CA116339/CA/NCI NIH HHS/United States ; 5R25CA116339/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology/*surgery ; *Carcinoma, Ductal, Breast ; *Carcinoma, Lobular ; Female ; Humans ; *Magnetic Resonance Imaging ; Mastectomy ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Preoperative Care ; Retreatment ; Retrospective Studies ; Risk Factors ; SEER Program ; Treatment Outcome ; }, abstract = {Existing evidence suggests that preoperative breast magnetic resonance imaging (MRI) might not improve surgical outcomes in the general breast cancer population. To determine if patients differentially benefit from breast MRI, we examined surgical outcomes-initial mastectomy, reoperation, and final mastectomy rates-among patients grouped by histologic type. We identified women diagnosed with early-stage breast cancer from 2004 to 2007 in the SEER-Medicare dataset. We classified patients as having invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), mixed ductal/lobular carcinoma (IDLC) or other histologic type. Medicare claims were used to identify breast MRI and definitive surgeries during the initial surgical treatment episode. We used propensity score methods to account for the differential likelihood of exposure to MRI. Of the 20,332 patients who met our inclusion criteria for this study, 12.2 % had a preoperative breast MRI. Patients with ILC as compared to other histologic groups were most likely to receive MRI [OR 2.32; 95 % CI (2.02-2.67)]. In the propensity score-adjusted analyses, breast MRI was associated with an increased likelihood of an initial mastectomy for all patients and among all histologic subgroups. Among patients with ILC, having a breast MRI was associated with lower odds of a reoperation [OR 0.59; 95 % CI (0.40-0.86)], and an equal likelihood of a final mastectomy compared to similar patients without a breast MRI. Overall and among patients with IDC and IDLC, breast MRI was not significantly associated with a likelihood of a reoperation but was associated with greater odds of a final mastectomy. Our study provides evidence in support of the targeted use of preoperative breast MRI among patients with ILC to improve surgical planning; it does not provide evidence for the routine use of breast MRI among all newly diagnosed breast cancer patients or among patients with IDC.}, } @article {pmid24304285, year = {2014}, author = {Vacas-Córdoba, E and Bastida, H and Pion, M and Hameau, A and Ionov, M and Bryszewska, M and Caminade, AM and Majoral, JP and Muñoz-Fernández, MÁ}, title = {HIV-antigens charged on phosphorus dendrimers as tools for tolerogenic dendritic cells-based immunotherapy.}, journal = {Current medicinal chemistry}, volume = {21}, number = {16}, pages = {1898-1909}, doi = {10.2174/0929867321666131129114022}, pmid = {24304285}, issn = {1875-533X}, mesh = {Cell Movement ; Cytokines/metabolism ; Dendrimers/chemistry/*therapeutic use ; Dendritic Cells/*immunology/metabolism ; HIV Antigens/*immunology ; Humans ; *Immunotherapy ; Phosphorus/*chemistry ; }, abstract = {AIMS: The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides.

MATERIALS & METHODS: The HIV derived peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit.

RESULTS: All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity to stimulate allogenic naïve T cells in vitro and impeded the production of pro-inflammatory cytokines.

CONCLUSIONS: The phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response. The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical antiinflammatory agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.}, } @article {pmid24301790, year = {2013}, author = {Zhang, Y and Meng, FY and Li, WL and Zhou, CX and Guan, Z and Fan, HY}, title = {Association of chemotactic factor receptor 5 gene with breast cancer.}, journal = {Genetics and molecular research : GMR}, volume = {12}, number = {4}, pages = {5289-5300}, doi = {10.4238/2013.November.7.4}, pmid = {24301790}, issn = {1676-5680}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology/therapy ; Female ; Gene Expression Regulation, Neoplastic ; *Genetic Association Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Receptor, ErbB-2 ; Receptors, CCR5/*genetics/metabolism ; Risk Factors ; }, abstract = {We designed a 2-stage study to investigate chemotactic factor receptor 5 (CCR5) gene expression in breast cancer tissues and axillary lymph nodes and analyze the association between the CCR5-Î"32 gene polymorphism and the clinical features and prognosis of breast cancer patients. The first stage examined 72 cases of invasive ductal carcinoma and axillary lymph node tissue, 50 cases of breast fibroadenoma tissue, and 40 cases of normal breast tissue. The tissues specimens were embedded in paraffin, and CCR5 expression was detected using immunohistochemical methods. C-erbB-2, p53, Ki-67, estrogen receptor, and progesterone receptor expression were also detected in the breast cancer tissues. The second stage examined 35 cases of surgically removed tissue. Relative expression levels of CCR5 messenger RNA (mRNA) in primary foci, axillary lymph node, and cancer-adjacent tissues of the breast cancer and breast fibroadenoma samples were detected using real-time quantitative reverse transcription-polymerase chain reaction assay. We found that 1) CCR5 mRNA relative expression levels in breast cancer tissue were significantly higher than those in adjacent normal tissue (P < 0.01) and benign tumors (P < 0.05). The relative CCR5 mRNA relative expression level between phase II and phase III breast cancer tissues was statistically significant (P < 0.05). The CCR5 mRNA relative expression level between adjacent normal tissues and fibroadenoma tissues was not significantly different (P > 0.05). 2) Relative CCR5 mRNA expression level was significantly higher in metastatic lymph node tissues than that in non-metastatic lymph nodes (P < 0.05), and 3) CCR5 expression in breast cancer tissue was positively correlated with axillary lymph node metastasis (chi-square = 4.982, P = 0.026, r = 0.305). CCR5 expression was mildly and positively correlated with the oncogene C-erbB-2 (P < 0.05, r = 0.291). 4) CCR5 expression in breast cancer tissue was not correlated with age, menopause, maximum tumor size, tumor phase, p53, Ki-67, estrogen receptor, progesterone receptor, or other clinical features (P > 0.05). We concluded that CCR5 expression significantly increases in breast cancer tissues and metastatic lymph nodes. CCR5 plays a role in breast cancer development and axillary lymph node metastasis. It can be used indirectly as an indicator of axillary lymph node metastasis and prognosis.}, } @article {pmid24293915, year = {2012}, author = {Deshmukh, SP and Mane, AD and Hardas, VS and Karnik, SV}, title = {Papillary carcinoma of the breast- case reports and review of literature regarding management guidelines.}, journal = {The Indian journal of surgery}, volume = {74}, number = {6}, pages = {510-512}, pmid = {24293915}, issn = {0972-2068}, abstract = {Papillary carcinoma of the breast is a very rare entity accounting for approx 1 % of all breast carcinomas. The diagnosis is difficult due to different clinical and radiological features. Pathological diagnosis is conclusive. Being aware of the diagnostic difficulties and differences in management from the more commonly reported IDC, makes it easier to treat these patients. Because this is an uncommon disease, we report here 2 cases recently diagnosed and treated in our hospital. We have also reviewed the literature regarding the diagnosis, treatment and prognosis of these patients.}, } @article {pmid24292672, year = {2014}, author = {Zhong, J and Cao, RX and Liu, JH and Liu, YB and Wang, J and Liu, LP and Chen, YJ and Yang, J and Zhang, QH and Wu, Y and Ding, WJ and Hong, T and Xiao, XH and Zu, XY and Wen, GB}, title = {Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein.}, journal = {Oncogene}, volume = {33}, number = {48}, pages = {5546-5558}, doi = {10.1038/onc.2013.500}, pmid = {24292672}, issn = {1476-5594}, mesh = {Adult ; Aged ; Animals ; Biomarkers, Tumor/analysis ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cyclin D1/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Heterografts ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/*metabolism ; Mice ; MicroRNAs ; Middle Aged ; Mutagenesis, Site-Directed ; Neoplasm Grading ; Oligonucleotide Array Sequence Analysis ; Protein-Arginine N-Methyltransferases/*metabolism ; Real-Time Polymerase Chain Reaction ; Tissue Array Analysis ; Transfection ; }, abstract = {Human protein arginine N-methyltransferase 2 (PRMT2, HRMT1L1) is a protein that belongs to the arginine methyltransferase family, and it has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. In this study, we provide evidences for the negative effect of PRMT2 on breast cancer cell proliferation in vitro and in vivo. Morever, cyclin D1, one of the key modulators of cell cycle, was found to be downregulated by PRMT2, and PRMT2 was further shown to suppress the estrogen receptor α-binding affinity to the activator protein-1 (AP-1) site in cyclin D1 promoter through indirect binding with AP-1 site, resulting in the inhibition of cyclin D1 promoter activity in MCF-7 cells. Furthermore, a positive correlation between the expression of PRMT2 and cyclin D1 was confirmed in the breast cancer tissues by using tissue microarray assay. In addition, PRMT2 was found to show a high absent percentage in breast caner cell nuclei and the nuclear loss ratio of PRMT2 was demonstrated to positively correlate with cyclin D1 expression and the increasing tumor grade of invasive ductal carcinoma. Those results offer an essential insight into the effect of PRMT2 on breast carcinogenesis, and PRMT2 nuclear loss might be an important biological marker for the diagnosis of breast cancer.}, } @article {pmid24290611, year = {2014}, author = {Conson, M and Trojano, L and Vitale, C and Mazzarella, E and Allocca, R and Barone, P and Grossi, D and Santangelo, G}, title = {The role of embodied simulation in mental transformation of whole-body images: evidence from Parkinson's disease.}, journal = {Human movement science}, volume = {33}, number = {}, pages = {343-353}, doi = {10.1016/j.humov.2013.10.006}, pmid = {24290611}, issn = {1872-7646}, mesh = {Adult ; Aged ; Body Image/*psychology ; Confusion/physiopathology/psychology ; Discrimination, Psychological/physiology ; Female ; Functional Laterality/*physiology ; Humans ; Imagination/*physiology ; Male ; Middle Aged ; Orientation/*physiology ; Parkinson Disease/*physiopathology/*psychology ; Pattern Recognition, Visual/*physiology ; Problem Solving/*physiology ; Reference Values ; Rotation ; }, abstract = {It has been repeatedly demonstrated that mentally performing an action and mentally transforming body-parts entail simulation of one's own body movements, consistent with predictions of embodied cognition theories. However, the involvement of embodied simulation in mental transformation of whole-body images is still disputed. Here, we assessed own body transformation in Parkinson's disease (PD) patients with symptoms most affecting the left or the right body side. PD patients were required to perform left-right judgments on front-facing or back-facing human figures, and a letter rotation task. Results demonstrated that PD patients were selectively impaired in judging the side of back-facing human figures corresponding to their own most affected side, but performed as well as healthy subjects on mental transformation of front-facing bodies and on letter rotation. These findings demonstrate a parallel impairment between motor and mental simulation mechanisms in PD patients, thus highlighting the specific contribution of embodied cognition to mental transformation of whole-body images.}, } @article {pmid25031990, year = {2013}, author = {Radcliff, L}, title = {Breast cancer and autism.}, journal = {Journal of the advanced practitioner in oncology}, volume = {4}, number = {2}, pages = {113-117}, pmid = {25031990}, issn = {2150-0878}, abstract = {Case Study Amy is a 44-year-old woman with severe autism. She lives with her sister Susan, who is her caregiver and guardian. Amy is ambulatory and able to dress and feed herself. She is a healthy individual with no other significant comorbidities. She walks daily and enjoys her sister's company. Amy's life expectancy is greater than 10 years. However, she is difficult to care for medically, as she will not allow a physical examination and strikes out when strangers try to touch her. She is nonverbal and unable to participate in decision-making. INITIAL DIAGNOSIS Amy has a history of breast cancer diagnosed 2 years ago, originally presenting as a stage I lesion (T2N0) that was palpated by her caregiver while bathing. She underwent right simple mastectomy with sentinel lymph node resection. Susan recalls that the mastectomy was a very challenging ordeal, as Amy kept pulling out IV lines, drains, and dressings. Susan felt that Amy withdrew from her after the procedure as she most likely associated Susan with the cause of the pain, making her role as caregiver more difficult. Pathology confirmed an invasive ductal carcinoma, moderately differentiated, 2.4 cm, estrogen/progesterone receptor negative, HER2/neu negative, with negative surgical margins. Two right axillary sentinel lymph nodes were negative for disease. The standard of care for a patient with these tumor features is surgery plus adjuvant chemotherapy (National Comprehensive Cancer Network [NCCN], 2012). According to the Adjuvant Online! database (2012), Amy's risk for relapse was approximately 40% without adjuvant treatment; her risk for mortality was approximately 29%. After meeting with a medical oncologist, Amy did not receive adjuvant chemotherapy. According to Susan, she was not offered the choice, and the decision was not explained to them. She was simply told that it was not necessary. Aside from pathology, previous records were unavailable for review. Medical assessment of Amy's level of autism reveals marked impairments in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body posture, and gestures to regulate social interaction. She exhibits a total lack of development of spoken language, with no attempt to compensate through alternative modes of communication such as gesture. During the visit, she occupies herself with repetitive motor mannerisms. Susan believes that Amy struggles with overstimulation from tactile input. Therefore, she is combative with health-care providers and intolerant of invasive devices. Susan has an intimate understanding of Amy's ability to communicate her needs and wants through nonverbal changes. RECURRENCE Approximately 2 months ago, Amy began favoring her right arm and appeared to be in pain when participating in various activities. Susan became aware of Amy's pain issues by noticing that her posture was slightly altered and she was carrying herself differently. Further investigation with a CT scan showed concern for local disease recurrence involving the axillary lymph nodes. No distant metastases were seen. The standard of care for this diagnosis is surgical resection and consideration of radiation therapy, followed by adjuvant chemotherapy (NCCN, 2012). Susan does not want Amy to undergo further surgery and believes radiation would be too difficult to maneuver. The next best option would be a medical approach with chemotherapy as the main modality. DIFFICULT DECISIONS If treatment is pursued, the advanced practitioner will need to perform regular examinations and prescribe and monitor chemotherapy. The delivery of therapy, requiring frequent blood draws and IV access, will be a challenge for the health-care staff. The APN is apprehensive about the ability to accomplish these tasks safely given Amy's limited capacity to participate. The APN is also concerned with how treatment will affect Amy's life. The APN may have her own individual conflict of morals to contend with, given the limited understanding of the patient vs. nontreatment of a potentially curative malignancy. Chemotherapy is not an easy task for any patient to undertake, especially for a patient with challenges such as Amy has. Although Susan can give legal consent for her sister, Amy is unable to participate in this decision-making. Susan strongly believes that Amy's quality of life is much more important than the quantity. Withholding treatment may shorten the natural course of Amy's life, yet administering chemotherapy will alter the quality of life that she now enjoys without her understanding or consent. Should Amy receive chemotherapy or should Susan refuse treatment on her behalf?}, } @article {pmid26316951, year = {2013}, author = {Ramanathan, S and Chakrapani, V and Ramakrishnan, L and Goswami, P and Yadav, D and George, B and Sen, S and Rachakulla, H and Subramanian, T and Paranjape, RS}, title = {Factors Associated with Use of Latex Condom-Compatible Lubricants by Men Who Have Sex with Men in India: Implications for HIV Prevention.}, journal = {Journal of sexually transmitted diseases}, volume = {2013}, number = {}, pages = {161085}, pmid = {26316951}, issn = {2090-7893}, abstract = {We examined the prevalence and type of rectal lubricants use and factors associated with exclusive use of latex-condom compatible lubricants (water-based lubricants) among men who have sex with men (MSM) using data from a large-scale cross-sectional survey conducted in 2009/10 in three Indian states. Using time-location cluster sampling, 3880 MSM were recruited from cruising sites. We used multiple logistic regression to assess the association between type of lubricants used and sociodemographic and programmatic indicators. Among those who reported using lubricants (64%) more than half (53%) exclusively used water-based lubricants, less than one-tenth used exclusively oil-based lubricants, and nearly 40% used both water-based and oil-based lubricants. Factors associated with exclusive use of water-based lubricants were exposure to HIV prevention interventions (AOR: 6.18, 95% CI 4.82 to 7.92) and kothi-identified MSM-feminine/anal-receptive (AOR: 2.56, 95% CI 2.12 to 3.10). Targeted HIV interventions among MSM need to promote and distribute latex condom-compatible lubricants for use during anal sex-irrespective of their presumed or stated sexual role in anal sex, and educate them not to use oil-based lubricants with condoms.}, } @article {pmid26591725, year = {2012}, author = {Mabula, JB and Mchembe, MD and Chalya, PL and Giiti, G and Chandika, AB and Rambau, P and Masalu, N and Gilyomai, JM}, title = {Stage at diagnosis, clinicopathological and treatment patterns of breast cancer at Bugando Medical Centre in north-western Tanzania.}, journal = {Tanzania journal of health research}, volume = {14}, number = {4}, pages = {269-279}, pmid = {26591725}, issn = {1821-6404}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*pathology/*therapy ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Analysis ; Tanzania/epidemiology ; Treatment Outcome ; }, abstract = {Breast cancer, although reported to be the commonest female malignancy worldwide has not been extensively studied in north-western Tanzania. The aim of this retrospective review was to describe in our setting, the stage at diagnosis, clinicopathological and treatment patterns among patients with breast cancer. Data were analyzed using SPSS software system. A total of 384 patients were studied. The median age was 45 years (range 21 to 78 years). The male to female ratio was 1: 46.8. Most of the patients were premenopausal (63.8%) and presented late with advanced breast cancer disease. Majority of patients (63.0%) presented with stage III disease. Lymph node and distant metastasis at the time of diagnosis was reported in 70.8% and 21.4% of patients, respectively. Invasive ductal carcinoma (91.7%) was the most frequent histopathological type and most patients (63.8%) had poorly differentiated tumour. Patients with tumour size greater than 6cm had significantly high rate of lymph node metastasis (P=0.001) and presence of necrosis within the tumour (P=0.012) compared to patients with tumour size less than 6cm in diameter. Patients younger than 45 years had significantly high rate of lymph node metastasis compared to the patients above this age (P=0.0 11). Mastectomy was the main modality of treatment that was used in 99.5% of the patients. Adjuvant chemotherapy and radiotherapy was reported in 44.8% and 11.7% of patients, respectively. Hormonal therapy (tamoxifen) was given postoperatively to all patients. The overall five-year survival rate was 21.8%. The age of patient at diagnosis, stage of disease, extent of lymph node involvement and histological grade were found to be independent predictors of overall survival rate (P<0.001). Local recurrence was 17.7% and it was significantly related to the stage of disease (P=0.003) and non-adherent to adjuvant therapy (P=0.021). Breast cancer patients in this region are relatively young premenopausal women and mostly present late with advanced stage and high rate of lymph node metastasis. There is need to improve public enlightenment of breast cancer and set up screening centres to encourage early presentations.}, } @article {pmid25083433, year = {2012}, author = {Niu, L and Zhou, L and Xu, K}, title = {Cryosurgery of breast cancer.}, journal = {Gland surgery}, volume = {1}, number = {2}, pages = {111-118}, pmid = {25083433}, issn = {2227-684X}, abstract = {With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies.}, } @article {pmid24693200, year = {2012}, author = {Terunuma, H}, title = {Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004.}, journal = {Journal of stem cells & regenerative medicine}, volume = {8}, number = {3}, pages = {205-206}, pmid = {24693200}, issn = {0973-7154}, abstract = {INTRODUCTION: Cancer, the major killer disease of the century requires a multi-pronged approach and among the latest modalities of treatments, Immunotherapy occupies a promising role. Immunotherapy for cancer was first started to be practised in the NIH and cell based immunotherapy for cancer is in practice for the past three decades. ([1, 2]) There are several literatures from various countries on the successful application of cell based Immunotherapies for various solid tumours and haematological malignancies. ([3-8]) Our team's association with immune cells started when I was working on RNA transcriptome analysis to understand the immune system in HIV carriers which in turn required in vitro expansion of human Natural Killer (NK) cells. ([9]) This led to the customization of protocols which has resulted in successful in vitro expansion, activation of NK cells and T cells for Immunotherapy. The purpose of Biotherapy institute of Japan (BIJ) is to support research and clinical application of immune cells like NK cells, γδT cells, αβT cells, Cytotoxic T lymphocytes (CTL) and Dendritic cells (DC) for application as Autologous Immune Enhancement Therapy (AIET) to fight against cancer. AIET using NK cells, CTLs, DCs etc have been administered for more than 5000 patients since 2004 till date by BIJ.

PRINCIPLE OF AIET: For AIET using NK cells, the process involves separation of lymphocytes from the peripheral blood of the patient followed by selective NK cell expansion using the expansion kit (BINKIT, BIJ, JAPAN) without feeder layers and then infusion of the expanded-activated NK cells. ([10,11]) As reports suggest that the activity of peripheral blood NK cells are lower in cancer patients compared to normal individuals([12]) and as in vitro expansion of NK cells increases the cytotoxic ability 5 to 10 fold, ([13]) the NK cells are expanded in vivo and then infused to the patient in AIET. We are also working on combination immunotherapy using NK cells and CTLs and also NK cells and peptide pulsed DCs. The principle behind combining NK cells and CTLs is a dual advantage approach combining the innate immune system and adaptive immune system wherein the CTLs will kill the MHC expressing cancer cells while NK cells will kill the MHC non-expressing cancer cells also. ([10]) In case of NK cells and DCs, DCs will in turn activate the CTLs thereby giving rise to the dual advantage mentioned above. We have recently suggested that the AIET using expanded NK cells, particularly in combination with monoclonal antibody drugs, may be very useful tool for cancer immunotherapy. ([14].)

OUR EXPERIENCE: In our studies in NOG SCID mice, activated NK cells were shown to reduce the size of breast cancer cells (MDA-MB231) ([15]) and the volume of ascites also inhibiting lung metastasis of pleural effusion lymphoma (PEL) cells. ([16]) In a primary lung adenocarcinoma patient where AIET was administered in combination with Hyperthermia, the CEA values decreased from 4.8 ng/ml to 1.6 ng/ml, the SLX decreased from 30 U/ml to 27 U/ml, the IAP reduced from 300 μg/ml to 221 μg/ml along with resolution of the lung lesions in four months. A 55 year old woman treated for invasive ductal carcinoma of breast presented with metastasis to the lungs. She was then treated with trastuzumab in combination with multiple injections of activated natural killer (NK) cells (at two week intervals) following which the tumor markers decreased. Progression free survival was 10 months. ([11]) Fifty-two patients with advanced cancers in organs like lung, breast, colon, prostate, liver, kidney, ovary etc, refractory to conventional therapy when treated with a combination of hyperthermia and NK cell-and CTL-based immune cell therapy with low-dose chemotherapy, in 18 of 52 patients, objective responses was observed including one complete response (CR) and 17 partial responses (PR) evaluated according to to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Sixteen patients had stable disease (SD), whereas 18 had progressive disease (PD). Disease control rate was 66% including CR, PR and SD. After treatment for six months, the objective responses and disease control rate were 25% and 52%, respectively. There were no adverse effects in any of these patients. ([17].)

CONCLUSION: Cancer has to be tackled with a multipronged approach and combining NK cell and CTL cell based AIET with conventional modalities of treatments such as Surgery, Chemotherapy and Radiotherapy as well as other modalities like Hyperthermia, Proton Beam therapy and low dose chemotherapy is effective even in advanced cancers which are refractory to conventional therapeutic modalities.}, } @article {pmid24899990, year = {2011}, author = {Song, BI and Hong, CM and Lee, HJ and Kang, S and Jeong, SY and Kim, HW and Chae, YS and Park, JY and Lee, SW and Ahn, BC and Lee, J}, title = {Prognostic Value of Primary Tumor Uptake on F-18 FDG PET/CT in Patients with Invasive Ductal Breast Cancer.}, journal = {Nuclear medicine and molecular imaging}, volume = {45}, number = {2}, pages = {117-124}, pmid = {24899990}, issn = {1869-3474}, abstract = {PURPOSE: To determine the prognostic implications of pretreatment F-18 FDG PET/CT in patients with invasive ductal breast cancer (IDC), we evaluated the relationship between FDG uptake of the primary tumor and known prognostic parameters of breast cancer. Prognostic significance of tumoral FDG uptake for the prediction of progression-free survival (PFS) was also assessed.

MATERIALS AND METHODS: Fifty-five female patients with IDC who underwent pretreatment F-18 FDG PET/CT were enrolled. The maximum standardized uptake value of the primary tumor (pSUVmax) was compared with clinicopathological parameters including tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor2 (HER2), axillary lymph node (LN) metastasis, and stage. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.

RESULTS: A high pSUVmax was significantly related to a higher stage of tumor size (P < 0.05), grade (P < 0.001), and stage (P < 0.001). pSUVmax was significantly higher in ER-negative tumors (P < 0.001), PR-negative tumors (P < 0.001), and positive LN metastasis (P < 0.01), but not different according to HER2 status. pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (10.6 ± 5.1 vs. 4.7 ± 3.5, P < 0.001). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.6 to be the optimal cutoff for predicting PFS (sensitivity; 86.7%, specificity; 82.5%). The patients with a high pSUVmax (more than 6.6) had significantly shorter PFS compared to patients with a low pSUVmax (P < 0.0001).

CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/CT could be used as a good surrogate marker for the prediction of progression in patients with IDC.}, } @article {pmid24753864, year = {2011}, author = {Van den Rul, N and Han, SN and Van Calsteren, K and Neven, P and Amant, F}, title = {Postpartum breast cancer behaves differently.}, journal = {Facts, views & vision in ObGyn}, volume = {3}, number = {3}, pages = {183-188}, pmid = {24753864}, issn = {2032-0418}, abstract = {BACKGROUND AND AIM: Previous studies suggest a worse prognosis for postpartum breast cancer (PPBC) diagnosed within the first 12 months following delivery. We investigated this hypothesis in our setting through a retrospective pilot study.

METHODS: A retrospective multicentre paired case-control study of breast cancer patients diagnosed under age 45 from the UZ Leuven database or affiliated centres. We compared disease outcome of women with a PPBC and those without a pregnancy associated breast cancer (PABC). They were matched for the following prognostic markers: age at diagnosis, tumour type, characteristics and stage. Kaplan-Meier statistics were applied for overall and disease free survival.

RESULTS: 53 PPBC cases were matched with 103 controls. All PPBC patients were diagnosed with an invasive ductal carcinoma. Axillary lymph nodes were involved in 56.6% of cases and 13% were primary metastasized at diagnosis. A third was triple-negative and another third was HER-2-positive.The 5-year overall survival was 60% and 84% respec-tively for PPBC cases and control group. 5-year disease free survival was respectively 53% and 68%.

CONCLUSIONS: We confirm that postpartum breast cancer behaves more aggressively than the matched non-PABC group. Longer follow-up and extension of the study group are necessary to confirm these findings.}, } @article {pmid26162120, year = {2010}, author = {Ein-Dor, T and Mikulincer, M and Doron, G and Shaver, PR}, title = {The Attachment Paradox: How Can So Many of Us (the Insecure Ones) Have No Adaptive Advantages?.}, journal = {Perspectives on psychological science : a journal of the Association for Psychological Science}, volume = {5}, number = {2}, pages = {123-141}, doi = {10.1177/1745691610362349}, pmid = {26162120}, issn = {1745-6916}, abstract = {Bowlby's (1969/1982) attachment theory has generated an enormous body of research and conceptual elaborations. Although attachment theory and research propose that attachment security provides a person with many adaptive advantages during all phases of the life cycle, numerous studies indicate that almost half of the human species can be classified as insecurely attached or insecure with respect to attachment. It seems odd that evolution left humans in this vulnerable position unless there are some advantages, under at least some conditions, to anxious and avoidant attachment styles. We argue that a social group containing members with different attachment patterns may be more conducive to survival than a homogeneous group of securely attached individuals. In making this argument, we extend the scope of attachment theory and research by considering a broader range of adaptive functions of insecure attachment strategies. We also present preliminary data to support our argument.}, } @article {pmid24778819, year = {2009}, author = {Pleşan, DM and Georgescu, CV and Ciobotea, S and Pătrană, N and Mitroi, L and Pleşan, C}, title = {Immunohistochemical evaluation of hormone receptors with predictive value in mammary carcinomas.}, journal = {Current health sciences journal}, volume = {35}, number = {3}, pages = {184-189}, pmid = {24778819}, issn = {2067-0656}, abstract = {AIMS. Immunohistochemical evaluation of hormone receptors (ER, PR) and correlation of immunohistochemical and morpho-clinical data. METHOD. The study was performed on paraffin-embedded and HE stained tissues originating from 100 cases of invasive mammary carcinoma. Monoclonal antibodies anti-estrogen and anti progesterone receptors were used for the immunohistochemical study. The detection system was EnVision HRP and the visualization system was 3-3' diaminobenzidine tetrahydrochloride (DAB). The evaluation of the result was performed using the Allred score. REZULTS. The majority of the studied cases (57%) expressed both types of hormone receptors and in 32% of the cases the hormone receptors were completely absent. The rest of the cases presented a heterogeneous phenotype: 7% presented the ER-/PR+ type and 4%, the ER+/PR- type. Compared with the classical phenotype (ER+/PR-), ER+/PR- tumors were more frequent at patients over 50 years. The tumors with ER+/PR- were larger than the ER+/PR+ and they were of the invasive ductal carcinoma type with an Allred score for ER under 6. CONCLUSION. The predictive value is amplified when the ER status is correlated with the PR status because the heterogeneous phenotypes are identified, especially the ER+/PR- phenotype which have an aggressive behavior and the lowest response to tamoxifen therapy.}, } @article {pmid26680921, year = {2003}, author = {Lee, MJ and Jeon, HJ}, title = {Evaluation of Her-2/neu in Breast Cancer: Comparison of Immunohistochemistry and Polymerase Chain Reaction.}, journal = {Cancer research and treatment}, volume = {35}, number = {2}, pages = {96-101}, doi = {10.4143/crt.2003.35.2.96}, pmid = {26680921}, issn = {1598-2998}, abstract = {PURPOSE: In breast cancer, Her-2/neu amplification/overexpression predicts a poor clinical outcome, and enhanced survival benefits have been reported with Her-2/neu targeted therapy. Currently, there are several methods for assessing the amplification/overexpression of Her-2/neu, each having advantages and disadvantages. The aim of this work was to establish a reproducible, sensitive and specific method of testing for Her-2/neu, which could be used in diagnostic pathology laboratories.

MATERIALS AND METHODS: We compared the immunohistochemistry (IHC) detection of Her-2/neu overexpression, with differential polymerase chain reaction (PCR) to assess the gene amplification of the Her-2/ neu, in 163 cases of invasive ductal carcinoma of the breast using paraffin-embedded tissue. In addition, assessment of the appropriate cut off points was established.

RESULTS: The overexpression of the Her-2/neu was detected in 39 (23.9%) cases, and its amplification in 37 (22.7%) cases. The methods were positive in 21.5% of cases and negative in 74.8%. There was a 96.3% concordance between the two methods. The sensitivity and specificity of IHC, compared with PCR, were 94.6 and 96.8%, respectively.

CONCLUSION: We conclude that the automation of PCR-based Her-2/neu testing approaches is expected to play an increasing role in the future of Her-2/neu testing. Also, we have demonstrated that IHC is a sensitive and specific method for assessing Her-2/neu stati in breast cancer, compared to PCR. The current study indicates that moderate, or strong, complete membrane staining in> or =10% of tumor cells provides an appropriate cut off point compared with PCR.}, } @article {pmid26680869, year = {2002}, author = {Yoo, J and Choi, HJ and Lee, HJ and Kang, SJ and Kim, BK and Shim, SI and Kang, CS}, title = {Invasive Ductal Carcinoma of the Male Breast: A Case Report and Review of the Literature.}, journal = {Cancer research and treatment}, volume = {34}, number = {3}, pages = {239-242}, doi = {10.4143/crt.2002.34.3.239}, pmid = {26680869}, issn = {1598-2998}, abstract = {Breast carcinomas are an uncommon neoplastic condition in men, accounting for only 1% of all breast cancers, and less than 1% of all malignancies in men. A 70-year-old man who presented a right breast mass was found to have infiltrating ductal carcinoma. We herein report the case with a review of the literature.}, } @article {pmid26141267, year = {2001}, author = {Hanson, EL and Hershberger, RE}, title = {Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy.}, journal = {Journal of genetic counseling}, volume = {10}, number = {5}, pages = {397-415}, pmid = {26141267}, issn = {1573-3599}, abstract = {Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families.}, } @article {pmid24283273, year = {2014}, author = {Brask, JB and Talman, ML and Wielenga, VT}, title = {Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {122}, number = {7}, pages = {593-598}, doi = {10.1111/apm.12198}, pmid = {24283273}, issn = {1600-0463}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Neuroendocrine/*diagnosis/pathology ; Chromogranin A/*analysis ; Female ; Humans ; Prognosis ; Sensitivity and Specificity ; Synaptophysin/*analysis ; Tissue Array Analysis/*methods ; }, abstract = {Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining for neuroendocrine markers and the fact that NCB may only show slight neuroendocrine morphology that can easily be overlooked, NCB is often underdiagnosed. Consequently, there is a need for fast and reliable detection method for NCB. Here, we take a first step toward finding an easy way of identifying NCB by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained for the neuroendocrine markers chromogranin A and synaptophysin. Cases positive in more than 50% of the tumor cells were accepted in accordance with WHO (2003) standards of NCB. Sensitivity and specificity for TMA sections vs whole-mount sections were found to be 100% and 97.8%, respectively, suggesting that TMA analysis is a reliable method for NCB detection.}, } @article {pmid24275943, year = {2014}, author = {Erro, R and Lees, AJ and Moccia, M and Picillo, M and Penco, S and Mosca, L and Vitale, C and Barone, P}, title = {Progressive parkinsonism, balance difficulties, and supranuclear gaze palsy.}, journal = {JAMA neurology}, volume = {71}, number = {1}, pages = {104-107}, doi = {10.1001/jamaneurol.2013.5149}, pmid = {24275943}, issn = {2168-6157}, mesh = {Aged ; CADASIL/diagnosis/genetics/physiopathology ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Male ; Ocular Motility Disorders/diagnosis/physiopathology ; Parkinsonian Disorders/*diagnosis/*physiopathology ; Supranuclear Palsy, Progressive/*diagnosis/*physiopathology ; Syndrome ; Vestibule, Labyrinth/*physiopathology ; }, abstract = {A 76-year-old man presented with a 4-year history of a progressive parkinsonian syndrome. It started with slowness of gait and mood dysfunction. Symptoms slowly progressed and further included occasional unexplained falls. On examination, he showed a severe parkinsonian syndrome featuring bradykinesia, rigidity (axial > appendicular), and positive pull-test finding. Moreover, there was an upgaze supranuclear palsy and slow saccades on vertical plane. Magnetic resonance imaging was performed that revealed significant basal ganglia lesions and white matter hyperintensities, including periventricular regions and both frontal and temporal subcortical areas, along with moderate widespread atrophy and ventricular enlargement. Here, we reveal the pathological diagnosis and discuss the approach to the clinical data.}, } @article {pmid24273662, year = {2013}, author = {Francis, IM and Al-Ayadhy, B and Al-Awadhi, S and Kapila, K and Al-Mulla, F}, title = {Prevalence and correlation of human papilloma virus and its types with prognostic markers in patients with invasive ductal carcinoma of the breast in kuwait.}, journal = {Sultan Qaboos University medical journal}, volume = {13}, number = {4}, pages = {527-533}, pmid = {24273662}, issn = {2075-051X}, abstract = {OBJECTIVES: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers.

METHODS: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters.

RESULTS: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters.

CONCLUSION: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected.}, } @article {pmid24262078, year = {2014}, author = {Giordani, L and Del Pinto, T and Vincentini, O and Felli, C and Silano, M and Viora, M}, title = {Two wheat decapeptides prevent gliadin-dependent maturation of human dendritic cells.}, journal = {Experimental cell research}, volume = {321}, number = {2}, pages = {248-254}, doi = {10.1016/j.yexcr.2013.11.008}, pmid = {24262078}, issn = {1090-2422}, mesh = {Celiac Disease/*therapy ; Cell Differentiation/*drug effects/immunology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/*drug effects/physiology ; Gliadin/*adverse effects ; Humans ; Oligopeptides/*pharmacology ; Plant Proteins, Dietary/*pharmacology ; Receptors, CCR7/metabolism ; Triticum/*chemistry ; }, abstract = {Celiac disease (CD) is a small intestinal enteropathy, triggered in susceptible individuals by the ingestion of dietary gluten. Dendritic cells (DC) are instrumental in the generation and regulation of immune responses and oversee intestinal immune homeostasis promoting and maintaining oral tolerance to food antigens. The aim of this study was to monitor the effect of peptic-tryptic digest of gliadin (PT-gliadin) on the maturation of human monocyte-derived DC and the impact of pDAV and pRPQ decapeptides in the modulation of PT-gliadin-induced phenotypic and functional DC maturation. Immature DC (iDC) were challenged in vitro with PT-gliadin. In some experiments iDC were pre-treated with pDAV or pRPQ and after 2h PT-gliadin was added to the cultures. We found that PT-gliadin up-regulates the expression of the maturation markers HLA-DR, CD83, CD80 and CD86. The functional consequence of PT-gliadin treatment of iDC is a significant increase in IL-12, TNF-alpha production as well as in their T cell stimulatory capacity. On the contrary, the digest of zein had no effect on DC maturation. Interestingly, we found that pre-treatment of iDC with pDAV or pRPQ decapeptides significantly prevents the functional maturation of DC induced by PT-gliadin. On the other hand, pDAV and pRPQ did not revert the PT-gliadin-induced phenotypic maturation of DC. Here we report, for the first time, that naturally occurring peptides are able to prevent the gliadin-dependent DC maturation. This finding could have implication for CD, raising the perspective of a potential therapeutic strategy alternative to a gluten free diet.}, } @article {pmid24262018, year = {2013}, author = {Taliano, RJ and Lu, S and Singh, K and Mangray, S and Tavares, R and Noble, L and Resnick, MB and Yakirevich, E}, title = {Calretinin expression in high-grade invasive ductal carcinoma of the breast is associated with basal-like subtype and unfavorable prognosis.}, journal = {Human pathology}, volume = {44}, number = {12}, pages = {2743-2750}, pmid = {24262018}, issn = {1532-8392}, support = {P20 GM103421/GM/NIGMS NIH HHS/United States ; P20GM103421/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Calbindin 2/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {Calretinin, a calcium-binding protein, is a widely used marker for mesothelial differentiation. There is accumulating evidence of calretinin expression in epithelial and mesenchymal malignancies, as well. The objectives of this study were to (1) further delineate the expression of calretinin in grade 3 breast carcinomas in the context of molecular subtypes and (2) identify the impact of calretinin expression on overall and disease-free survival. On the basis of immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), cytokeratin 5/6, and epidermal growth factor receptor, 214 grade 3 invasive ductal carcinomas were stratified into 36 luminal A, 63 luminal B, 24 HER2 positive, 81 basal-like (including 13 metaplastic carcinomas), and 10 unclassified. Tissue microarrays were analyzed for immunohistochemical expression of calretinin. High-level calretinin expression was identified in a significant proportion of basal-like (54.3%), HER2 (33.3%), and unclassified (30%) tumors. In contrast, luminal A and B subtypes demonstrated high-level calretinin expression in only 11.1% and 12.7%, respectively (P < .0001). Within the basal-like group, 38.5% of the metaplastic carcinomas demonstrated high-level expression, associated predominantly with the epithelial component and squamous metaplasia. High-level calretinin expression was strongly associated with decreased overall survival in the entire cohort of grade 3 cancer (P = .0096) and in the basal-like group (P = .039). Multivariate analysis revealed that both tumor stage and high-level calretinin expression were independent predictors of overall survival (P = .0002 and P = .0023, respectively). In conclusion, high-level calretinin expression is most common in grade 3 tumors with a basal-like phenotype and is associated with poor overall survival.}, } @article {pmid24260046, year = {2013}, author = {Thorat, D and Sahu, A and Behera, R and Lohite, K and Deshmukh, S and Mane, A and Karnik, S and Doke, S and Kundu, GC}, title = {Association of osteopontin and cyclooxygenase-2 expression with breast cancer subtypes and their use as potential biomarkers.}, journal = {Oncology letters}, volume = {6}, number = {6}, pages = {1559-1564}, pmid = {24260046}, issn = {1792-1074}, abstract = {Breast cancer is one of the most common malignant tumors among females worldwide and remains a leading cause of cancer-related mortality. Due to the heterogeneous clinical nature of breast cancer, it is necessary to identify new biomarkers that are associated with tumor growth, angiogenesis and metastasis. Osteopontin (OPN) and cyclooxygenase-2 (COX-2) are known to be overexpressed in invasive breast cancer and their overexpression is associated with aggressive histological and clinical features. The present study assessed OPN and COX-2 expression in various subtypes of breast cancer. The expression of OPN and COX-2 was analyzed using immunohistochemistry (IHC) in a cohort of 67 invasive ductal breast carcinoma patients. The statistical analysis was performed using standard statistical software SPSS version 18.0. The associations between OPN and COX-2 and the human epidermal growth factor receptor type 2 (HER2)-overexpressing and non-HER2-overexpressing subtypes were evaluated using the Mann-Whitney U test. The mean OPN level was significantly higher in the HER2-overexpressing subtype compared with the non-HER2-overexpressing subtype. Furthermore, the mean COX-2 expression levels were higher in the HER2-overexpressing subtype compared with the luminal A, luminal B or triple-negative groups. It is well known that carcinomas overexpressing HER2/neu have a worse prognosis than luminal tumors. Hence, it may be hypothesized that an elevated expression of OPN and COX-2 in a HER2-overexpressing subtype may contribute to a more aggressive behavior and be used as diagnostic and prognostic markers in breast cancer.}, } @article {pmid24255847, year = {2013}, author = {Lee, KE and Kim, HH and Shin, HJ and Cha, JH}, title = {Stereotactic biopsy of the breast using a decubitus table: comparison of histologic underestimation rates between 11- and 8-gauge vacuum-assisted breast biopsy.}, journal = {SpringerPlus}, volume = {2}, number = {}, pages = {551}, pmid = {24255847}, issn = {2193-1801}, abstract = {PURPOSE: To evaluate efficacy of the stereotactic vacuum-assisted breast biopsy(SVAB) using a decubitus table and to compare histologic underestimation rate between 11gauge(G)- and 8G-probes.

MATERIALS AND METHODS: Pathologic results of SVAB using a decubitus table of 210(120 with 11G; 90 with 8G)-procedures in 208-women(median age, 48.8 years; range, 27-73 years) were retrospectively reviewed. SVAB was performed for suspicious microcalcification without mass on MMG and US. Surgury was performed for the diagnosis of malignant or high-risk lesion (65(31.0%)). Patients with benign diagnosis (120(57.1%)) underwent MMG follow-up (mean, 340-days). Histologic underestimation was defined as the need to upgrade ADH to DCIS or IDC, and DCIS to IDC at surgery. We analyzed the difference of procedure time, core number and core weight between 11G- and 8G-groups. Statistical significance was determined with chi-square test and 95%-CI for histologic underestimation, and student T-test for comparing two-groups.

RESULTS: Targeting was successful in all 210-biopsies on specimen radiographs. Mean core number, core weight and procedure time were 17.5 (17.5 ± 4.9), 1.57 g (1.57 ± 0.56), 34.5 min (34.5 ± 16.4) with 11G-probe, and 9.6 (9.6 ± 6.2), 1.83g (1.83 ± 0.93), 22.1 min (22.1 ± 12.5) with 8G-probe. Findings in 120 (57.1%) of the biopsies were benign, 36 (17.2%) were high-risk, and 54 (25.7%) were malignant. Two (6.25%) of 32 cases of ADH were upgraded to DCIS in 11G-group, and 2 (9.09%) of 22 in 8G-group. No case of DCIS was upgraded to IDC. There was no increase of complication in 8G-group than 11G-group.

CONCLUSION: SVAB using a decubitus table is safe and effective method for the evaluation of suspicious microcalcification, and there was no significant difference between 11G- and 8G-probes. But, SVAB with 8G-probe is significantly more time efficient and effective procedure.}, } @article {pmid24254879, year = {2014}, author = {Rehman, S and Husnain, SM}, title = {A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.}, journal = {Biological trace element research}, volume = {157}, number = {1}, pages = {24-29}, doi = {10.1007/s12011-013-9865-7}, pmid = {24254879}, issn = {1559-0720}, mesh = {Breast/*chemistry ; Breast Neoplasms/*chemistry/epidemiology ; Copper/analysis ; Female ; Humans ; Iron/analysis ; Limit of Detection ; Probability ; Risk Factors ; Spectrophotometry, Atomic ; Zinc/analysis ; }, abstract = {The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.}, } @article {pmid24252817, year = {2015}, author = {Nam, SY and Ko, ES and Han, BK and Shin, S and Ko, EY and Shin, JH and Hahn, SY}, title = {Ultrasonographic hyperechoic lesions of the breast: are they always benign?.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {56}, number = {1}, pages = {18-24}, doi = {10.1177/0284185113512482}, pmid = {24252817}, issn = {1600-0455}, mesh = {Adipose Tissue/*diagnostic imaging ; Adult ; Aged ; *Artifacts ; Breast Neoplasms/*diagnostic imaging ; Diagnostic Errors/prevention & control/*statistics & numerical data ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Prevalence ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Ultrasonography, Mammary/methods/*statistics & numerical data ; }, abstract = {BACKGROUND: Most of the breast lesions show hypoechogenicity relative to fat on ultrasonography. The frequency and malignancy rate of hyperechoic lesions are not investigated in a large series.

PURPOSE: To evaluate the frequency and malignancy rate of hyperechoic lesions on breast sonography and to investigate sonographic characteristics that may predict malignancy in hyperechoic breast lesions.

MATERIAL AND METHODS: Radiologic reports of 16,416 patients who underwent breast sonography between 2007 and 2008 were searched using "hyperechoic", "echogenic" or "heterogeneous echoic" to describe lesions. Sonographic findings were evaluated according to the Breast Imaging Reporting and Data System lexicon. Clinical records including follow-up and pathologic findings were also reviewed. We calculated the frequency of hyperechoic lesions and their malignancy rate. Differences in sonographic appearances between benign and malignant lesions were also investigated.

RESULTS: Among the 16,416 patients, 103 (0.6%) hyperechoic lesions were identified (mean size, 1.79 cm). Of these 103 lesions, 27 (26.2%) were pathologically evaluated and five (4.9%, 4 invasive ductal carcinoma and 1 mucinous carcinoma) were confirmed as malignant. Among the 819 malignant lesions diagnosed using sonography-guided core needle biopsy, five (0.6%) were hyperechoic. In benign lesions, fat necrosis and fibroadenoma were common pathologic diagnoses. Malignant lesions were more likely to have irregular shape (P = 0.003), non-parallel orientation (P = 0.002), non-circumscribed margin (P = 0.007), and a hypoechoic area (P = 0.027) than benign lesions. All hyperechoic carcinomas were seen as suspicious masses on mammograms.

CONCLUSION: Hyperechoic masses are very rare and mostly benign. As an adjunct to mammography, the imaging findings reported here could help to avoid misdiagnosis for malignant hyperechoic lesion.}, } @article {pmid24252758, year = {2013}, author = {Wojcinski, S and Stefanidou, N and Hillemanns, P and Degenhardt, F}, title = {The biology of malignant breast tumors has an impact on the presentation in ultrasound: an analysis of 315 cases.}, journal = {BMC women's health}, volume = {13}, number = {}, pages = {47}, pmid = {24252758}, issn = {1472-6874}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/pathology ; Carcinoma, Lobular/*diagnostic imaging/metabolism/pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; *Ultrasonography, Mammary ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the relation of some ultrasound morphological parameters to biological characteristics in breast carcinoma.

METHODS: Ultrasound data from 315 breast masses were collected. We analyzed the ultrasound features of the tumors according to the ACR BI-RADS®-US classification system stratified by hormone receptor status, HER2 status, histology grade, tumor type (ductal versus lobular), triple-negativity, breast density, tumor size, lymph node involvement and patient's age.

RESULTS: We found a variety of ultrasound features that varied between the groups. Invasive lobular tumors were more likely to have an angulated margin (39% versus 22%, p = 0.040) and less likely to show posterior acoustic enhancement (3% versus 16%, p = 0.023) compared to invasive ductal carcinoma. G3 tumors were linked to a higher chance of posterior acoustic enhancement and less shadowing and the margin of G3 tumors was more often described as lobulated or microlobulated compared to G1/G2 tumors (67% versus 46%, p = 0.001). Tumors with an over-expression of HER2 exhibited a higher rate of architectural distortions in the surrounding tissue, but there were no differences regarding the other features. Hormone receptor negative tumors were more likely to exhibit a lobulated or microlobulated margin (67% versus 50%, p = 0.037) and less likely to have an echogenic halo (39% versus 64%, p = 0.001). Furthermore, the posterior acoustic feature was more often described as enhancement (33% versus 13%, p = 0.001) and less often as shadowing (20% versus 47%, p < 0.001) compared to hormone receptor positive tumors.

CONCLUSION: Depending on their biological and clinical profile, breast cancers are more or less likely to exhibit the typical criteria for malignancy in ultrasound. Moreover, certain types of breast cancer tend to possess criteria that are usually associated with benign masses. False-negative diagnosis may result in serious consequences for the patient. For the sonographer it is essential to be well aware of potential variations in the ultrasound morphology of breast tumors, as described in this paper.}, } @article {pmid24248542, year = {2014}, author = {Buhmeida, A and Dallol, A and Merdad, A and Al-Maghrabi, J and Gari, MA and Abu-Elmagd, MM and Chaudhary, AG and Abuzenadah, AM and Nedjadi, T and Ermiah, E and Al-Thubaity, F and Al-Qahtani, MH}, title = {High fibroblast growth factor 19 (FGF19) expression predicts worse prognosis in invasive ductal carcinoma of breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {3}, pages = {2817-2824}, pmid = {24248542}, issn = {1423-0380}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/*mortality/pathology ; Female ; Fibroblast Growth Factors/analysis/*biosynthesis ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Receptors, Estrogen/analysis/metabolism ; }, abstract = {Metabolic diseases like diabetes and obesity are major risk factors for breast cancer. Aberrant expression of metabolic effectors such as fibroblast growth factor 19 (FGF19) could be therefore associated with the disease. The expression of FGF19 was examined in 193 archival breast tumor samples by immunohistochemistry and evaluated semi-quantitatively by determining the staining index and correlating it with clinicopathological parameters using Fisher's exact test. The correlation between FGF19 expression and 5-year disease-specific survival rate was determined using the univariate Kaplan-Meier analysis. The prognostic value of FGF19 expression was evaluated using the multivariate Cox regression analysis. Of the 193 tumors analyzed, 40% were classified with low FGF19 expression, whereas 60% were categorized as tumors with high FGF19 expression. There was a highly significant correlation between high FGF19 expression and patients' age (p = 0.008) as well as 5-year disease-specific survival (p = 0.001). However, FGF19 expression did not show any significant correlations with other clinicopathological parameters, including hormonal status, tumor grade, tumor size, or lymph node status. Univariate Kaplan-Meier log rank analysis showed that patients with high FGF19 expression exhibited a significantly shorter disease-specific 5-year survival (p = 0.007). This effect was exacerbated by lymph node metastasis (p = 0.001), negative estrogen receptor (ER) status (p = 0.002), or old age (p = 0.013). Multivariate analysis showed that high FGF19 expression could be an independent prognostic marker of disease-specific survival in breast cancer patients (p = 0.030). Quantification of FGF19 expression appears to provide valuable prognostic information in breast cancer, particularly in older patients with lymph node metastasis and negative ER status.}, } @article {pmid24236052, year = {2013}, author = {Chen, X and Qiu, J and Yang, D and Lu, J and Yan, C and Zha, X and Yin, Y}, title = {MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9.}, journal = {PloS one}, volume = {8}, number = {11}, pages = {e78794}, pmid = {24236052}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology/surgery ; Carcinoma, Ductal, Breast/*enzymology/secondary/surgery ; Disease-Free Survival ; Enzyme Induction ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; MCF-7 Cells ; Matrix Metalloproteinase 9/*genetics/metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; Proportional Hazards Models ; Proto-Oncogene Proteins c-mdm2/*physiology ; Tumor Burden ; Up-Regulation ; Young Adult ; }, abstract = {The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors. The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r[2] = 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown.}, } @article {pmid24229822, year = {2013}, author = {Lafeuille, MH and Gravel, J and Zhang, J and Gorsh, B and Figliomeni, M and Lefebvre, P}, title = {Association between consistent omalizumab treatment and asthma control.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {1}, number = {1}, pages = {51-57}, doi = {10.1016/j.jaip.2012.08.006}, pmid = {24229822}, issn = {2213-2198}, mesh = {Anti-Asthmatic Agents/*therapeutic use ; Antibodies, Anti-Idiotypic/*therapeutic use ; Antibodies, Monoclonal, Humanized/*therapeutic use ; Asthma/*drug therapy ; Cohort Studies ; Female ; Humans ; Male ; Medication Adherence/*statistics & numerical data ; Middle Aged ; Omalizumab ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Omalizumab is indicated for patients with moderate-to-severe allergic asthma with inadequately controlled symptoms.

OBJECTIVE: We evaluated the association between consistent omalizumab treatment and asthma control.

METHODS: Health insurance claims from the MarketScan database (2002Q1-2011Q2) were analyzed. Asthmatic patients with ≥12 months of continuous insurance coverage after the first omalizumab claim (index date) after 6 months of continuous omalizumab use were included. A 12-month landmark period was used to assess treatment consistency, defined as uninterrupted treatment without a gap of ≥28 days in omalizumab use. The effect of consistent omalizumab treatment on asthma control between months 13 and 24 was evaluated. Multivariate time-varying Cox regressions were also conducted to assess the adjusted effect of treatment interruption on asthma control from month 1 to month 24.

RESULTS: A total of 3044 patients (mean age, 48.5 years; female, 62%) formed the study population. Patients consistent with omalizumab treatment at 12 months (39% of patients) were less likely to have an uncontrolled asthma event during months 13 to 24 with only 49% of patients experiencing one event compared with 54% in the non consistent subgroup (P = .02). In addition, consistent omalizumab treatment at 12 months was associated with a 51% reduction in the mean number of asthma-related emergency department (ED) visits per patient and a 28% reduction in asthma-related hospitalizations. Multivariate analyses corroborated these findings (hazard ratio for consistent vs non-consistent: risk of short-acting β2-agonists prescription, oral corticosteroids prescription, ED visit, or hospitalization, 0.76; 95% CI, 0.69-0.83]).

CONCLUSION: This analysis showed that consistent omalizumab treatment was associated with significant reductions in ED visits and hospitalizations.}, } @article {pmid24229021, year = {2013}, author = {Ochiai, T and Igari, K and Furuyama, T and Ito, H and Mitsunori, Y and Aihara, A and Kumagai, Y and Iida, M and Odajima, H and Tanaka, S and Arii, S and Yamazaki, S}, title = {Favorable response after gemcitabine-radiotherapy for invasive pancreatic intraductal papillary mucinous neoplasm: a case report.}, journal = {International surgery}, volume = {98}, number = {4}, pages = {340-345}, pmid = {24229021}, issn = {2520-2456}, mesh = {Adenocarcinoma, Mucinous/diagnosis/*therapy ; Antimetabolites, Antineoplastic/*therapeutic use ; Biomarkers, Tumor/blood ; Carcinoma, Pancreatic Ductal/diagnosis/*therapy ; Carcinoma, Papillary/diagnosis/*therapy ; *Chemoradiotherapy ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Diagnosis, Differential ; Diagnostic Imaging ; Humans ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/diagnosis/*therapy ; Radiotherapy Dosage ; Gemcitabine ; }, abstract = {The efficacy of chemoradiotherapy for invasive pancreatic ductal carcinoma derived from an intraductal papillary mucinous neoplasm (IPMN) has not been established. The subject of the present report was a 53-year-old man admitted for the treatment of IPMN. The tumor, located in the pancreatic body, was of the mixed type of IPMN, and it involved the branch duct, where it was 38 mm in diameter, and the main duct, where it was 6 mm in diameter. Distal pancreatectomy was performed and the postoperative course was uneventful; however, histopathologic diagnosis revealed invasive ductal carcinoma with a positive surgical margin in the pancreatic duct. Although total pancreatectomy was recommended, chemoradiotherapy (50.4-Gy irradiation and gemcitabine) was preferred by the patient. At 9-month follow up, computed tomography and magnetic resonance imaging showed a cystic mass at the surgical margin of the pancreas. Endoscopic ultrasonography showed a 44-mm cystic lesion with nodules in the remnant pancreas, on the basis of which he underwent total pancreatectomy. Pathologic examination of the resected specimen revealed absence of the epithelium at the surgical margin of the main pancreatic duct, and malignant cells were not detected.}, } @article {pmid24229009, year = {2013}, author = {Nozoe, T and Mori, E and Iguchi, T and Ezaki, T}, title = {New criteria to predict tumor recurrence in invasive ductal carcinoma of the breast.}, journal = {International surgery}, volume = {98}, number = {4}, pages = {283-288}, pmid = {24229009}, issn = {2520-2456}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Prognosis ; Risk Assessment ; }, abstract = {Incidence of triple-negative breast cancer (TNBC), which is cancer without expression of ER, PgR, and HER2, and nuclear grade (NG) are closely correlated with malignant potential of breast cancer. However, criteria to determine aggressiveness of breast cancer based on these factors have not been elucidated. The aim of this study was to create criteria using these factors to predict tumor recurrence in invasive ductal carcinoma (IDC) of the breast. One hundred and seventy-nine patients with IDC of the breast, which had been treated by surgical resection, were included. One point was added for each factor of the two categories of TNBC and NG 3. The sum of the scores (TGS 0, 1, or 2) was calculated. Significant difference was observed between TGS and the incidence of tumor recurrence (P < 0.0001). Moreover, significant differences were observed regarding relapse-free survival (RFS) between patients with TGS 0 and TGS 1 (P < 0.0001) and patients with TGS 1 and TGS 2 (P = 0.024). TGS might contain a clinical advantage as a useful predictor for tumor recurrence of IDC of the breast and could classify prognosis of the patients with a preferable stratification.}, } @article {pmid24228207, year = {2013}, author = {Gregg, A and Leddy, R and Lewis, M and Irshad, A}, title = {Acquired arteriovenous fistula of the breast following ultrasound guided biopsy of invasive ductal carcinoma.}, journal = {Journal of clinical imaging science}, volume = {3}, number = {}, pages = {38}, pmid = {24228207}, issn = {2156-7514}, abstract = {Image guided large-core breast biopsies are commonly performed procedures with relatively rare complications. The majority of these complications are minor, though at times more significant vascular injuries can occur with these biopsies as demonstrated by this case. Patient developed a pulsatile vascular breast mass after an ultrasound guided breast biopsy of invasive ductal carcinoma. Sonographic evaluation of this new breast mass demonstrated this mass to represent an arteriovenous fistula (AVF). Though multiple therapies are available for an iatrogenic fistula within the breast, the AVF was surgically excised in this case as it was immediately adjacent to a known cancer.}, } @article {pmid24225229, year = {2013}, author = {Zhou, H and Shi, R and Wei, M and Zheng, WL and Zhou, JY and Ma, WL}, title = {The expression and clinical significance of HERC4 in breast cancer.}, journal = {Cancer cell international}, volume = {13}, number = {1}, pages = {113}, pmid = {24225229}, issn = {1475-2867}, abstract = {BACKGROUND: Increasing evidence suggest that ubiquitin-proteasome system (UPS) plays a key role in tumorigenesis. HERC4 is a recently identified ubiqutin ligase. However, the expression status and biological functions of HERC4 in cancers are not clearly.

METHODS: We evaluated the HERC4 expression in breast cancer cell lines and breast tumor tissues by quantitative real-time PCR and western blot analysis. To investigate the clinicopathological significance of HERC4, immunohistochemistry analysis for HERC4 was performed on a tissue microarray including 13 benign fibroadenoma, 15 intraductal carcinoma, 120 histologically confirmed invasive ductal carcinoma. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of HERC4, when HERC4 positive expression percentage was above 60%, tumor was defined as "positive".

RESULTS: HERC4 was up-regulated in breast cancer cell lines and breast tumor tissues compared to non-tumorigenic cell line and adjacent normal breast tissues. According to ROC analysis, HERC4 positive expression was detected in 1/16 (6.3%) of normal breast tissue, in 3/13 (23.1%) of fibroadenoma, in 6/15 (40%) of intraductal carcinoma and 66/120 (55%) of invasive ductal carcinoma. Positive expression of HERC4 was positively correlated with pT status, pN status, clinical stage and histological grade of patients with invasive ductal carcinoma (p < 0.05).

CONCLUSIONS: Our findings suggest that HERC4 was a significant diagnostic marker for invasive ductal carcinoma of the breast.}, } @article {pmid24224997, year = {2014}, author = {Vaidya, JS and Wenz, F and Bulsara, M and Tobias, JS and Joseph, DJ and Keshtgar, M and Flyger, HL and Massarut, S and Alvarado, M and Saunders, C and Eiermann, W and Metaxas, M and Sperk, E and Sütterlin, M and Brown, D and Esserman, L and Roncadin, M and Thompson, A and Dewar, JA and Holtveg, HM and Pigorsch, S and Falzon, M and Harris, E and Matthews, A and Brew-Graves, C and Potyka, I and Corica, T and Williams, NR and Baum, M and , }, title = {Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial.}, journal = {Lancet (London, England)}, volume = {383}, number = {9917}, pages = {603-613}, doi = {10.1016/S0140-6736(13)61950-9}, pmid = {24224997}, issn = {1474-547X}, support = {07/60/49/DH_/Department of Health/United Kingdom ; 10/104/07/DH_/Department of Health/United Kingdom ; HTA/07/60/49/DH_/Department of Health/United Kingdom ; }, mesh = {Aged ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/surgery ; Female ; Humans ; Intraoperative Care/methods/mortality ; Kaplan-Meier Estimate ; Mastectomy, Segmental/methods/mortality ; Middle Aged ; Neoplasm Recurrence, Local/mortality/prevention & control ; Radiotherapy/methods/mortality ; Treatment Outcome ; }, abstract = {BACKGROUND: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival.

METHODS: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684.

FINDINGS: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1-5·1) for TARGIT versus 1·3% (0·7-2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1-4·2) versus 1·1% (0·5-2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0-9·7] vs EBRT 1·7% [0·6-4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5-4·3] for TARGIT vs 1·9% [1·1-3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8-2·5] vs 3·5% [2·3-5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7-5·8) for TARGIT versus 5·3% (3·9-7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029).

INTERPRETATION: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT.

FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.}, } @article {pmid24217642, year = {2014}, author = {Brennan, SB and D'Alessio, D and Liberman, L and Giri, D and Brogi, E and Morris, EA}, title = {Cancelled stereotactic biopsy of calcifications not seen using the stereotactic technique: do we still need to biopsy?.}, journal = {European radiology}, volume = {24}, number = {4}, pages = {907-912}, pmid = {24217642}, issn = {1432-1084}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/methods ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Calcinosis/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology ; Female ; Humans ; Mammography/*statistics & numerical data ; Middle Aged ; Retrospective Studies ; Stereotaxic Techniques ; }, abstract = {OBJECTIVE: To determine the frequency of cancelled stereotactic biopsy due to non-visualisation of calcifications, and assess associated features and outcome data.

METHODS: A retrospective review was performed on 1,874 patients scheduled for stereotactic-guided breast biopsy from 2009 to 2011. Medical records and imaging studies were reviewed.

RESULTS: Of 1,874 stereotactic biopsies, 76 (4 %) were cancelled because of non-visualisation of calcifications. Prompt histological confirmation was obtained in 42/76 (55 %). In 28/76 (37 %) follow-up mammography was performed, and 7/28 subsequently underwent biopsy. Of 27 without biopsy, 21 (78 %) had follow-up. Nine cancers (9/49, 18 %) were found: 6 ductal carcinoma in situ (DCIS), 3 infiltrating ductal carcinoma (IDC). Of 54 patients with either biopsy or at least 2 years' follow-up, 9 (17 %) had cancer (95 % CI 8-29). Cancer was present in 7/42 (17 %, 95 % CI 7-31 %) lesions that had prompt histological confirmation (DCIS = 5, IDC = 2) and in 2/28 (7 %, 95 % CI 0.8-24 %) lesions referred for follow-up (DCIS = 1, IDC = 1). Neither calcification morphology (P = 0.2), patient age (P = 0.7), breast density (P = 1.0), personal history (P = 1.0) nor family history of breast cancer (P = 0.5) had a significant association with cancer.

CONCLUSION: Calcifications not visualised on the stereotactic unit are not definitely benign and require surgical biopsy or follow-up. No patient or morphological features were predictive of cancer.

KEY POINTS: • Half of cancelled stereotactic biopsies were due to non-visualisation of calcified foci. • This reflects the improved detection of calcifications by digital mammography. • Calcifications too faint for the stereotactic technique require alternative biopsy or follow-up • 17 % of patients with biopsy or at least 2 years' follow-up had cancer. • No patient/morphological features were found to aid selection for re-biopsy vs. follow-up.}, } @article {pmid24215986, year = {2014}, author = {Tibon, R and Levy, DA}, title = {Temporal texture of associative encoding modulates recall processes.}, journal = {Brain and cognition}, volume = {84}, number = {1}, pages = {1-13}, doi = {10.1016/j.bandc.2013.10.003}, pmid = {24215986}, issn = {1090-2147}, mesh = {Adolescent ; Adult ; Brain/*physiology ; Cues ; Evoked Potentials ; Female ; Humans ; Male ; *Memory, Episodic ; Mental Recall/*physiology ; Time Factors ; Young Adult ; }, abstract = {Binding aspects of an experience that are distributed over time is an important element of episodic memory. In the current study, we examined how the temporal complexity of an experience may govern the processes required for its retrieval. We recorded event-related potentials during episodic cued recall following pair associate learning of concurrently and sequentially presented object-picture pairs. Cued recall success effects over anterior and posterior areas were apparent in several time windows. In anterior locations, these recall success effects were similar for concurrently and sequentially encoded pairs. However, in posterior sites clustered over parietal scalp the effect was larger for the retrieval of sequentially encoded pairs. We suggest that anterior aspects of the mid-latency recall success effects may reflect working-with-memory operations or direct access recall processes, while more posterior aspects reflect recollective processes which are required for retrieval of episodes of greater temporal complexity.}, } @article {pmid24209961, year = {2013}, author = {Luncsford, PJ and Manvilla, BA and Patterson, DN and Malik, SS and Jin, J and Hwang, BJ and Gunther, R and Kalvakolanu, S and Lipinski, LJ and Yuan, W and Lu, W and Drohat, AC and Lu, AL and Toth, EA}, title = {Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions.}, journal = {DNA repair}, volume = {12}, number = {12}, pages = {1043-1052}, pmid = {24209961}, issn = {1568-7856}, support = {R56 CA078391/CA/NCI NIH HHS/United States ; GM 72711/GM/NIGMS NIH HHS/United States ; CA 78391/CA/NCI NIH HHS/United States ; R01 GM072711/GM/NIGMS NIH HHS/United States ; R01 CA078391/CA/NCI NIH HHS/United States ; }, mesh = {Binding Sites ; Biocatalysis ; Cell Cycle Proteins/genetics/metabolism ; DNA/metabolism ; DNA Damage ; DNA Glycosylases/chemistry/*metabolism ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry/*metabolism ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Mutation ; Protein Binding ; Protein Stability ; }, abstract = {MutY homologue (MYH) is a DNA glycosylase which excises adenine paired with the oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxoG, or G(o)) during base excision repair (BER). Base excision by MYH results in an apurinic/apyrimidinic (AP) site in the DNA where the DNA sugar-phosphate backbone remains intact. A key feature of MYH activity is its physical interaction and coordination with AP endonuclease I (APE1), which subsequently nicks DNA 5' to the AP site. Because AP sites are mutagenic and cytotoxic, they must be processed by APE1 immediately after the action of MYH glycosylase. Our recent reports show that the interdomain connector (IDC) of human MYH (hMYH) maintains interactions with hAPE1 and the human checkpoint clamp Rad9-Rad1-Hus1 (9-1-1) complex. In this study, we used NMR chemical shift perturbation experiments to determine hMYH-binding site on hAPE1. Chemical shift perturbations indicate that the hMYH IDC peptide binds to the DNA-binding site of hAPE1 and an additional site which is distal to the APE1 DNA-binding interface. In these two binding sites, N212 and Q137 of hAPE1 are key mediators of the MYH/APE1 interaction. Intriguingly, despite the fact that hHus1 and hAPE1 both interact with the MYH IDC, hHus1 does not compete with hAPE1 for binding to hMYH. Rather, hHus1 stabilizes the hMYH/hAPE1 complex both in vitro and in cells. This is consistent with a common theme in BER, namely that the assembly of protein-DNA complexes enhances repair by efficiently coordinating multiple enzymatic steps while simultaneously minimizing the release of harmful repair intermediates.}, } @article {pmid24207087, year = {2014}, author = {Cao, XL and Bao, W and Zhu, SG and Wang, LH and Sun, MH and Wang, L and Men, YM and Xue, J}, title = {Contrast-enhanced ultrasound characteristics of breast cancer: correlation with prognostic factors.}, journal = {Ultrasound in medicine & biology}, volume = {40}, number = {1}, pages = {11-17}, doi = {10.1016/j.ultrasmedbio.2013.08.014}, pmid = {24207087}, issn = {1879-291X}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; *Phospholipids ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; *Sulfur Hexafluoride ; Ultrasonography, Mammary/*methods ; }, abstract = {The purpose of the work described here was to investigate the correlation of contrast-enhanced ultrasound (CEUS) characteristics with prognostic factors in breast cancer. Forty-five consecutive breast cancer patients were studied with CEUS. All patients were diagnosed with invasive ductal carcinoma on the basis of biopsy or surgery results. Lack of blood perfusion of the tumor was identified in 2 cases; blood perfusion was observed in 43 cases. Enhancement was heterogeneous in 25 cases, and centripetal in 25 cases. A blood perfusion defect was present in 27 cases. Enhancement shape was irregular in 37 cases, margins were poorly defined in 34 cases, and penetrating vessels were present in 32 cases. Compared with the surrounding normal tissue, tumor tissue had faster rising times and times to peak and higher peak intensities and wash-in slopes; the differences between the two groups were statistically significant (p < 0.05). Compared with the interior of the tumor, the periphery had faster times to peak and higher peak intensities and wash-in slopes (p < 0.05). Heterogeneous enhancement, perfusion defect, centripetal enhancement and penetrating vessels were correlated with prognosis (p < 0.05). Overall, some CEUS characteristics of breast cancer were associated with prognostic factors that can predict breast cancer prognosis in vivo.}, } @article {pmid24203627, year = {2013}, author = {Gojis, O and Kubecova, M and Rosina, J and Vranova, J and Celko, M and Frajerova, D and Zmrhal, J and Zahumensky, J and Bacova, T and Baca, V and Mandys, V and Kucera, E}, title = {Expression of selected proteins in breast cancer brain metastases.}, journal = {Folia histochemica et cytobiologica}, volume = {51}, number = {3}, pages = {213-218}, doi = {10.5603/FHC.2013.0030}, pmid = {24203627}, issn = {1897-5631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/diagnosis/*metabolism/secondary ; Breast Neoplasms/diagnosis/*metabolism ; Carcinoma/diagnosis/*metabolism ; ErbB Receptors/genetics/metabolism ; Estrogen Receptor alpha/genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/genetics/metabolism ; Middle Aged ; Nuclear Receptor Coactivator 3/genetics/metabolism ; PAX2 Transcription Factor/genetics/metabolism ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.}, } @article {pmid24192092, year = {2013}, author = {Mesquita, M and Froes, F}, title = {Hospital admissions for herpes zoster in Portugal between 2000 and 2010.}, journal = {Acta medica portuguesa}, volume = {26}, number = {5}, pages = {531-536}, pmid = {24192092}, issn = {1646-0758}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Herpes Zoster/*epidemiology ; Humans ; Infant ; Male ; Middle Aged ; Patient Admission/*statistics & numerical data ; Portugal/epidemiology ; Retrospective Studies ; Time Factors ; Young Adult ; }, abstract = {INTRODUCTION AND OBJECTIVES: Herpes zoster and post-herpetic neuralgia increasing incidence is related to ageing. These conditions can be very debilitating and have an important impact in patients' quality of life. In an ageing population like the Portuguese, is expected that the burden of herpes zoster and post-herpetic neuralgia rises, nevertheless, a specific surveillance system for zoster does not exist in the country, and data regarding the incidence of herpes zoster and the burden of the disease in Portugal in the last decades was not found. In Portugal, the vaccine is still not available. Scaling the burden of disease is important to support public health policies regarding zoster vaccination.

MATERIAL AND METHODS: We carried out a retrospective analysis from encoded information from the Portuguese Ministery of Health database for hospital admissions which included all individuals with a primary diagnosis of Herpes Zoster (IDC-9-CM 053), who were discharged between 2000 and 2010.

RESULTS: In Portugal, between 2000 and 2010, 1 706 hospital admissions with primary diagnosis of herpes zoster occurred. The majority of the patients were elderly. Eleven percent of the patients had potentially severe immunocompromise. The predominant disease was uncomplicated herpes zoster, followed by nervous system and ophthalmic herpes zoster. Mean hospital stay length was 9.3 days, increasing with age. There was a 1% case fatality rate. Considering the 2000-2009 period and the adult population only, the average annual incidence rate of hospitalization with primary diagnosis of herpes zoster in Portugal was 1.9/100 000 inhabitants, increasing with age.

CONCLUSION: This study confirms that, in Portugal, severe herpes zoster is related to ageing and associated with significant morbidity, mortality and health resources allocation.}, } @article {pmid24177758, year = {2013}, author = {Petrelli, F and Barni, S}, title = {Response to neoadjuvant chemotherapy in ductal compared to lobular carcinoma of the breast: a meta-analysis of published trials including 1,764 lobular breast cancer.}, journal = {Breast cancer research and treatment}, volume = {142}, number = {2}, pages = {227-235}, doi = {10.1007/s10549-013-2751-3}, pmid = {24177758}, issn = {1573-7217}, mesh = {Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Carcinoma, Lobular/*drug therapy/pathology/surgery ; Female ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Publication Bias ; Treatment Outcome ; }, abstract = {Infiltrating lobular carcinoma (ILC) of the breast is associated with greater oestrogen receptor expression and poorer response to neoadjuvant chemotherapy, when compared to infiltrating ductal carcinoma (IDC). In order to compare the pathological complete response rate (pCR) and breast conserving surgery (BCS) in patients with ILC versus IDC treated with neoadjuvant chemotherapy, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated pCR, clinical response and BCS in patients with ILC that were treated with neoadjuvant chemotherapy. Random-effect models were adopted to estimate the summary odds ratio (OR), and the publication bias was evaluated using a funnel plot and Egger's regression asymmetry test. Seventeen studies were included (one randomized controlled trial, three prospective series and 13 retrospective trials), for a total of 12,645 IDCs and 1,764 ILCs to be compared. Ductal carcinoma of the breast was associated with a better pCR (from 5.9 to 16.7 %; OR = 3.1, 95 % CI 2.48-3.87, P < 0.00001) and rate of BCS (from 35.4 to 54.8 %; OR = 2.1, 95 % CI 1.8-2.45, P < 0.00001) compared to ILC. The overall pCR rates and BCS decreased in the ILCs compared with IDC when treated with neoadjuvant chemotherapy.}, } @article {pmid24177755, year = {2013}, author = {Yin, C and Li, H and Zhang, B and Liu, Y and Lu, G and Lu, S and Sun, L and Qi, Y and Li, X and Chen, W}, title = {RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition.}, journal = {Breast cancer research and treatment}, volume = {142}, number = {2}, pages = {297-309}, doi = {10.1007/s10549-013-2737-1}, pmid = {24177755}, issn = {1573-7217}, mesh = {Actin Depolymerizing Factors/metabolism ; Actins/*metabolism ; Animals ; Breast Neoplasms/*metabolism/*pathology ; Calgranulin A/*metabolism ; Calgranulin B/*metabolism ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line, Tumor ; Cell Movement ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; LIM-Homeodomain Proteins/metabolism ; Mice ; Mice, Inbred NOD ; Middle Aged ; NF-kappa B/metabolism ; Phosphorylation ; Polymerization ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/*metabolism ; Transcription Factors/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {S100A8/A9 proteins are members of EF-hand calcium-binding proteins secreted by neutrophils and activated monocytes. S100A8/A9 has cell growth-promoting activity at low concentrations by binding to the receptor for advanced glycation end products (RAGE). In this study, we report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on RAGE. In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. Interestingly, RAGE binding to S100A8/A9 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. Mechanistically, RAGE binding to S100A8/A9 stabilized Snail through the NF-κB signaling pathway. Based on these observations, RAGE expression in breast cancer cells was associated with lymph node and distant metastases in patients with invasive ductal carcinoma. Moreover, RAGE binding to S100A8/A9 promoted lung metastasis in vivo. In summary, our in vitro and in vivo results indicated that RAGE binding to S100A8/A9 played an important role in breast cancer invasion/metastasis. This study identified both RAGE and S100A8/A9 as potential anti-invasion targets for therapeutic intervention in breast cancer.}, } @article {pmid24176197, year = {2013}, author = {Ueda, S and Nakamiya, N and Matsuura, K and Shigekawa, T and Sano, H and Hirokawa, E and Shimada, H and Suzuki, H and Oda, M and Yamashita, Y and Kishino, O and Kuji, I and Osaki, A and Saeki, T}, title = {Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {514}, pmid = {24176197}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/diagnosis/*metabolism/*pathology ; Cell Proliferation ; Female ; Fluorodeoxyglucose F18 ; Glucose/*metabolism ; Hemoglobins/metabolism ; Humans ; Middle Aged ; Neoplasm Staging ; *Neovascularization, Pathologic ; Optical Imaging ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; Tumor Burden ; Young Adult ; }, abstract = {BACKGROUND: Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer.

METHODS: Fifty-five consecutive TNM stage I/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as "hotspots," while others were considered "uniform." The findings in either tumor type were compared with clinicopathological factors.

RESULTS: "Hotspot" tumors were significantly larger (P= 0.002) and exhibited significantly more advanced TNM stage (P=0.01), higher mitotic counts (P=0.01) and higher levels of FDG uptake (P=0.0004) compared with "uniform" tumors; however, other pathological variables were not significantly different between the two groups.

CONCLUSIONS: Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment.}, } @article {pmid24165314, year = {2013}, author = {Wisner, DJ and Hwang, ES and Chang, CB and Tso, HH and Joe, BN and Lessing, JN and Lu, Y and Hylton, NM}, title = {Features of occult invasion in biopsy-proven DCIS at breast MRI.}, journal = {The breast journal}, volume = {19}, number = {6}, pages = {650-658}, pmid = {24165314}, issn = {1524-4741}, support = {R01 CA116182/CA/NCI NIH HHS/United States ; T32 EB001631/EB/NIBIB NIH HHS/United States ; 1 T32 EB001631-04/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; }, abstract = {The purpose of this study is to determine if MRI BI-RADS criteria or radiologist perception correlate with presence of invasive cancer after initial core biopsy of ductal carcinoma in situ (DCIS). Retrospective search spanning 2000-2007 identified all core-biopsy diagnoses of pure DCIS that coincided with preoperative MRI. Two radiologists fellowship-trained in breast imaging categorized lesions according to ACR MRI BI-RADS lexicon and estimated likelihood of occult invasion. Semiquantitative signal enhancement ratio (SER) kinetic analysis was also performed. Results were compared with histopathology. 51 consecutive patients with primary core biopsy-proven DCIS and concurrent MRI were identified. Of these, 13 patients (25%) had invasion at excision. Invasion correlated significantly with presence of a mass for both readers (p = 0.012 and 0.001), rapid initial enhancement for Reader 1 (p = 0.001), and washout kinetics for Reader 2 (p = 0.012). Significant correlation between washout and invasion was confirmed by SER (p = 0.006) when threshold percent enhancement was sufficiently high (130%), corresponding to rapidly enhancing portions of the lesion. Radiologist perception of occult invasion was strongly correlated with true presence of invasion. These results provide evidence that certain BI-RADS MRI criteria, as well as radiologist perception, correlate with occult invasion after an initial core biopsy of DCIS.}, } @article {pmid24164747, year = {2015}, author = {Schmidt, M and Meyer, A and Cserer, A}, title = {The Bio:Fiction film festival: Sensing how a debate about synthetic biology might evolve.}, journal = {Public understanding of science (Bristol, England)}, volume = {24}, number = {5}, pages = {619-635}, pmid = {24164747}, issn = {0963-6625}, mesh = {Attitude ; *Motion Pictures ; *Public Opinion ; *Synthetic Biology ; }, abstract = {Synthetic biology (SB) is a new techno-scientific field surrounded by an aura of hope, hype and fear. Currently it is difficult to predict which way the public debate - and thus the social shaping of technology - is heading. With limited hard evidence at hand, we resort to a strategy that takes into account speculative design and diegetic prototyping, accessing the Bio:Fiction science film festival, and its 52 short films from international independent filmmakers. Our first hypothesis was that these films could be used as an indicator of a public debate to come. The second hypothesis was that SB would most likely not follow the debate around genetic engineering (framing technology as conflict) as assumed by many observers. Instead, we found good evidence for two alternative comparators, namely nanotechnology (technology as progress) and information technology (technology as gadget) as stronger attractors for an upcoming public debate on SB.}, } @article {pmid24160812, year = {2013}, author = {Wanis, ML and Wong, JA and Rodriguez, S and Wong, JM and Jabo, B and Ashok, A and Lum, SS and Solomon, NL and Reeves, ME and Garberoglio, CA and Senthil, M}, title = {Rate of re-excision after breast-conserving surgery for invasive lobular carcinoma.}, journal = {The American surgeon}, volume = {79}, number = {10}, pages = {1119-1122}, pmid = {24160812}, issn = {1555-9823}, mesh = {Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Carcinoma, Lobular/pathology/*surgery ; Cross-Sectional Studies ; Female ; Humans ; Mastectomy, Segmental/*statistics & numerical data ; Middle Aged ; Reoperation/statistics & numerical data ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Invasive lobular carcinoma (ILC) accounts for approximately 5 to 20 per cent of all breast cancers and is often multicentric. Despite pre- and intraoperative assessments to achieve negative margins, ILC is reported to be associated with higher rates of positive margin. This cross-sectional study examined patients with breast cancer treated at our institution from 2000 to 2010. The objective was to investigate the rate of re-excision resulting from positive or close margin (1 mm or less) in patients who underwent breast-conserving surgery (BCS) for ILC compared with invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). Of the 836 patients treated, 416 patients underwent BCS. The rate of re-excision after BCS for ILC was 35.1 versus 17.7 per cent for IDC and 20.0 per cent for DCIS (P = 0.04). Re-excisions were more often performed for positive margin in patients with ILC (11 of 37 [29.7%]) versus IDC (36 of 334 [10.8%]) and DCIS (five of 45 [11.1%];(P = 0.004). In this single-institution review, BCS for ILC had significantly higher rates of re-excision as a result of positive margins when compared with IDC and DCIS. Tumor size greater than 2 cm and lymph node involvement were identified as factors associated with positive surgical margin in ILC. The higher possibility of positive margins and the need for additional procedures should be discussed with patients undergoing BCS for ILC.}, } @article {pmid24159387, year = {2013}, author = {Friedman, EB and Chun, J and Schnabel, F and Schwartz, S and Law, S and Billig, J and Ivanoff, E and Moy, L and Axelrod, D and Guth, A}, title = {Screening prior to Breast Cancer Diagnosis: The More Things Change, the More They Stay the Same.}, journal = {International journal of breast cancer}, volume = {2013}, number = {}, pages = {327567}, pmid = {24159387}, issn = {2090-3170}, abstract = {Purpose. In November 2009, the U.S. Preventative Service Task Force (USPSTF) revised their breast cancer screening guidelines. We evaluated the pattern of screening subsequent to the altered guidelines in a cohort of women. Methods. Our database was queried for the following variables: age, race, method of diagnosis, mass palpability, screening frequency, histology, and stage. Statistical analyses were performed using Pearson's chi-square and Fisher's exact tests. Results. 1112 women were diagnosed with breast cancer from January 2010 to 2012. The median age at diagnosis was 60 years. Most cancers were detected on mammography (61%). The majority of patients had invasive ductal carcinoma (59%), stage 0 (23%), and stage 1 (50%) cancers. The frequency of screening did not change significantly over time (P = 0.30). However, nonregular screeners had an increased risk of being diagnosed with later stage breast cancer (P < 0.001) and were more likely to present with a palpable mass compared to regular screeners (56% versus 21%; P < 0.001). Conclusions. In our study, screening behavior did not significantly change in the years following the USPSTF guidelines. These results suggest that women who are not screened annually are at increased risk of a delay in breast cancer diagnosis, which may impact treatment options and outcomes.}, } @article {pmid24156087, year = {2013}, author = {Kashiwagi, S and Onoda, N and Asano, Y and Noda, S and Kawajiri, H and Takashima, T and Ohsawa, M and Kitagawa, S and Hirakawa, K}, title = {Clinical significance of the sub-classification of 71 cases mucinous breast carcinoma.}, journal = {SpringerPlus}, volume = {2}, number = {}, pages = {481}, pmid = {24156087}, issn = {2193-1801}, abstract = {OBJECTIVE: Mucinous breast carcinoma (MBC) is classified into mixed mucinous breast carcinoma (MMBC) and pure mucinous breast carcinoma (PMBC) based on whether the tumor is with or without a component of invasive ductal carcinoma, respectively. PMBC is subtyped into hypocellular PMBC (PMBC-A) and hypercellular PMBC (PMBC-B).

METHODS: Of 1,760 primary breast carcinomas, 71 were diagnosed as MBC, and were subtyped for comparison purposes.

RESULTS: Seventy-one of all breast cancers (4.0%) were MBC, and consisted of 23 MMBC, 32 PMBC-A and 16 PMBC-B. The MBC tumors were more often hormone receptor-positive and HER2-negative than non-MBC tumors. Patients with MMBC, PMBC-B or PMBC-A, in this order, had significantly higher recurrence rates than non-MBC cases (p=0.006, log-rank).

CONCLUSIONS: In the NCCN guidelines, MBC is also regarded as "a histological type with a favorable prognosis" in a uniform manner, and "treatment for a histological type with a favorable prognosis" is recommended. However, the results of this study suggest that sub-classification-based, individualized therapeutic strategies should be considered.}, } @article {pmid24155767, year = {2013}, author = {Sung, HJ and Maeng, YI and Kim, MK and Lee, SJ and Kang, SM and Bong, JG and Oh, HK}, title = {Breast carcinoma with choriocarcinomatous features: a case report.}, journal = {Journal of breast cancer}, volume = {16}, number = {3}, pages = {349-353}, pmid = {24155767}, issn = {1738-6756}, abstract = {Nongestational choriocarcinoma differentiation is extremely rare in breast neoplasms. It is characterized by tumor cells similar to chorionic trophoblastic cells, which react with human placental lactogen and human chorionic gonadotropin (hCG). A 56-year-old woman presented with a palpable right breast mass without past history of trophoblastic tumors. An F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed one focus with low accumulation of FDG in the right breast (maximum standardized uptake value, 1.98). The patient underwent a right mastectomy and biopsy of sentinel nodes. Microscopically, the tumor was a typical invasive ductal carcinoma with multiple foci of choriocarcinoma features. Immunohistochemistry showed that the tumor cells resembling choriocarcinoma were positive for hCG antibody, but negative for HER2/neu, estrogen receptor, and progesterone receptor. A pathologic diagnosis of breast carcinoma with choriocarcinomatous features was made. To our knowledge, this is the first report of invasive carcinoma with choriocarcinomatous features and an unusual finding of low accumulation in an F-18 FDG PET/CT scan in Korea.}, } @article {pmid24155762, year = {2013}, author = {Park, CS and Jung, NY and Kim, K and Jung, HS and Sohn, KM and Oh, SJ}, title = {Detection of breast cancer in asymptomatic and symptomatic groups using computer-aided detection with full-field digital mammography.}, journal = {Journal of breast cancer}, volume = {16}, number = {3}, pages = {322-328}, pmid = {24155762}, issn = {1738-6756}, abstract = {PURPOSE: We aimed to determine the sensitivity of computer-aided detection (CAD) applied to digital mammography in asymptomatic and symptomatic breast cancer patients.

METHODS: We retrospectively analyzed digital mammography and CAD images from 210 patients diagnosed with breast cancer. The patients were divided into symptomatic and asymptomatic groups. The sensitivity of CAD in both groups was assessed in relation to breast tissue density, histopathological type of breast cancer, and tumor size.

RESULTS: The detection rate of the CAD system was 87.8% in the asymptomatic group. The sensitivity in different tissue densities was 100% in fatty breasts (P1), 88.9% with scattered fibroglandular densities (P2), 94.4% in heterogeneously dense breasts (P3), and 66.7% in extremely dense breasts (P4). The detection rate of the CAD system in the symptomatic group was 87.2%, and the sensitivity was 90.5%, 90%, 86.6%, and 75% in P1-P4 breasts, respectively. In the asymptomatic group, the CAD system detected 90.3% of invasive ductal carcinomas, not otherwise specified (IDC-NOS) and 88.9% of ductal carcinomas in situ (DCIS), but did not detect other types of malignancy. In the symptomatic group, the CAD system detected 88.2% of IDC-NOS, 88.9% of DCIS and 75% of other types of malignancy. When analyzed according to tumor size, the sensitivity of CAD in the asymptomatic and symptomatic groups was 82.6% and 83.3% for tumors <1 cm, 76.5% and 82.4% for tumors between 1 and 2 cm, and 91.7% and 89% in tumors >2 cm.

CONCLUSION: The sensitivity of CAD was low in P4 breasts and high for tumors larger than 2 cm, with no statistically significant differences between the asymptomatic and symptomatic groups for IDC-NOS and DCIS. CAD showed greater sensitivity for other neoplasms in symptomatic patients.}, } @article {pmid24151510, year = {2013}, author = {Dialani, V and Mani, K and Johnson, NB}, title = {Chronic lymphocytic leukemia involving the breast parenchyma, mimicker of invasive breast cancer: differentiation on breast MRI.}, journal = {Case reports in medicine}, volume = {2013}, number = {}, pages = {603614}, pmid = {24151510}, issn = {1687-9627}, abstract = {Leukemic involvement of the breast is rare, particularly involvement by chronic lymphocytic leukemia (CLL). While concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in the breast is extremely rare, this association (CLL and carcinoma) has been described in other organs. We report here a case of a 58-year-old woman with concurrent invasive ductal carcinoma and CLL and describe the imaging features of CLL, particularly the differentiation on MRI.}, } @article {pmid24148254, year = {2013}, author = {Fearon, AE and Gould, CR and Grose, RP}, title = {FGFR signalling in women's cancers.}, journal = {The international journal of biochemistry & cell biology}, volume = {45}, number = {12}, pages = {2832-2842}, doi = {10.1016/j.biocel.2013.09.017}, pmid = {24148254}, issn = {1878-5875}, mesh = {Female ; Fibroblast Growth Factors/metabolism ; Genital Neoplasms, Female/*metabolism ; Humans ; Receptors, Fibroblast Growth Factor/*metabolism ; Signal Transduction ; }, abstract = {FGFs, in a complex with their receptors (FGFRs) and heparan sulfate (HS), are responsible for a range of cellular functions, from embryogenesis to metabolism. Both germ line and somatic FGFR mutations are known to play a role in a range of diseases, most notably craniosynestosis dysplasias, dwarfism and cancer. Because of the ability of FGFR signalling to induce cell proliferation, migration and survival, FGFRs are readily co-opted by cancer cells. Mutations in, and amplifications of, these receptors are found in a range of cancers with some of the most striking clinical findings relating to their contribution to pathogenesis and progression of female cancers. Here, we outline the molecular mechanisms of FGFR signalling and discuss the role of this pathway in women's cancers, focusing on breast, endometrial, ovarian and cervical carcinomas, and their associated preclinical and clinical data. We also address the rationale for therapeutic intervention and the need for FGFR-targeted therapy to selectively target cancer cells in view of the fundamental roles of FGF signalling in normal physiology.}, } @article {pmid24146864, year = {2013}, author = {Shan, M and Zhang, X and Liu, X and Qin, Y and Liu, T and Liu, Y and Wang, J and Zhong, Z and Zhang, Y and Geng, J and Pang, D}, title = {P16 and p53 play distinct roles in different subtypes of breast cancer.}, journal = {PloS one}, volume = {8}, number = {10}, pages = {e76408}, pmid = {24146864}, issn = {1932-6203}, mesh = {Adolescent ; Breast Neoplasms/*classification/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Down-Regulation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Mutation/genetics ; Risk Factors ; Signal Transduction/genetics ; Triple Negative Breast Neoplasms/genetics/pathology ; Tumor Suppressor Protein p53/genetics/*metabolism ; Up-Regulation/genetics ; }, abstract = {Breast cancers are heterogeneous and complex diseases, and subtypes of breast cancers may involve unique molecular mechanisms. The p16(INK4a) and p53 pathways are two of the major pathways involved in control of the cell cycle. They also play key roles in tumorigenesis. However, whether the roles of these pathways differ in the subtypes of breast cancer is unclear. Therefore, p16 and p53 expression were investigated in different breast cancer subtypes to ascertain their contributions to these cancers. A total of 400 cases of non-invasive ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), including the major molecular subtypes luminal-A, luminal-B, Her-2, and triple-negative subtypes, and 50 cases of normal controls were compared. Luminal-A cancers expressed the lowest level of p16 among the subtypes in DCIS, and the level of p16 expression was up-regulated in the luminal-A of IDC (P<0.008). Triple-negative breast cancers were characterized by a correlation of p53 overexpression with a high level of p16 expression. Luminal lesion types with high p16 expression in DCIS were found to be more likely to develop into aggressive breast cancers, possibly promoted by p53 dysfunction. Taken together, the present study suggest that p16 expression in luminal-A breast cancers is associated with their progression from DCIS to IDC, and both p53 and p16 expressions are important for the development of triple-negative breast cancers in DCIS and IDC.}, } @article {pmid24142686, year = {2014}, author = {Kaya, MG and Sarli, B and Akpek, M and Kaya, EG and Yarlioglues, M and Topsakal, R and Lam, YY}, title = {Evaluation of beta-blockers on left ventricular dyssynchrony and reverse remodeling in idiopathic dilated cardiomyopathy: A randomized trial of carvedilol and metoprolol.}, journal = {Cardiology journal}, volume = {21}, number = {4}, pages = {434-441}, doi = {10.5603/CJ.a2013.0149}, pmid = {24142686}, issn = {1898-018X}, mesh = {Adrenergic alpha-1 Receptor Antagonists/adverse effects/*therapeutic use ; Adult ; Aged ; Biomarkers/blood ; Carbazoles/adverse effects/*therapeutic use ; Cardiomyopathy, Dilated/diagnosis/*drug therapy/physiopathology ; Carvedilol ; Double-Blind Method ; Female ; Humans ; Male ; Metoprolol/adverse effects/*therapeutic use ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Propanolamines/adverse effects/*therapeutic use ; Prospective Studies ; Recovery of Function ; Stroke Volume/drug effects ; Time Factors ; Treatment Outcome ; Ventricular Dysfunction, Left/diagnosis/*drug therapy/physiopathology ; Ventricular Function, Left/*drug effects ; Ventricular Remodeling/*drug effects ; }, abstract = {BACKGROUND: The effect of b-blockage on cardiac dyssynchrony in idiopathic dilated cardio-myopathy (IDC) is unknown. This study evaluated the impact of carvedilol and metoprolol succinate on left ventricular (LV) dyssynchrony and reverse remodeling in IDC.

METHODS: In this small, prospective, double-blind study, we randomly assigned 81 IDC patients to receive carvedilol or metoprolol succinate. Echocardiographic measurements (dyssynchrony, LV volumes and ejection fraction [EF]) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were obtained at baseline and at first and sixth month of therapy.

RESULTS: A total of 74 (91%) patients completed all investigations at sixth month (38 and 36 taking carvedilol and metoprolol succinate, respectively). In the carvedilol group, reduction in LV end diastolic volume (D LVEDV at 6 months, 50 ± 15 mL to 40 ± 17 mL, p = 0.03) and increase in LVEF (D LVEF, 7 ± 2% to 5 ± 3%, p = 0.02) was higher compared to the metoprolol group. Also improvement in inter-ventricular dyssynchrony achieved with carvedilol was higher than metoprolol (D interventricular delay at 6 months, 11 ± 8 ms to 6 ± 7 ms, p = 0.03). However, improvement in intraventricular dyssynchrony was similar in the two groups (D intraventricular delay, 9 ± 7 ms to 9 ± 6 ms, p = 0.91). Improvements in LV mechanical dyssynchrony and reverse remodeling achieved with both drugs were accompanied by reduction in NT-proBNP levels in both carvedilol and metoprolol groups (1614 ± 685 pg/mL to 654 ± ± 488 pg/mL and 1686 ± 730 pg/mL to 583 ± 396 pg/mL, respectively, p < 0.001 for both).

CONCLUSIONS: Although reduction in LVEDV and increase in LVEF was higher with carvedilol, improvement in intraventricular dyssynchrony was similar in carvedilol and metoprolol groups.}, } @article {pmid24129963, year = {2014}, author = {Oh, Y and Oh, I and Morimoto, J and Uede, T and Morimoto, A}, title = {Osteopontin has a crucial role in osteoclast-like multinucleated giant cell formation.}, journal = {Journal of cellular biochemistry}, volume = {115}, number = {3}, pages = {585-595}, doi = {10.1002/jcb.24695}, pmid = {24129963}, issn = {1097-4644}, mesh = {Arthritis, Rheumatoid/*genetics/pathology ; Cell Differentiation/genetics ; Dendritic Cells/cytology/metabolism ; Giant Cells/drug effects ; Histiocytosis, Langerhans-Cell/*genetics/metabolism ; Humans ; Oligopeptides ; Osteoclasts/cytology/*metabolism ; Osteopontin/genetics/*metabolism ; RNA, Small Interfering ; }, abstract = {The osteoclast (OC) is a major player in the pathogenic bone destruction of inflammatory bone diseases such as rheumatoid arthritis and Langerhans cell histiocytosis. Recently, it was shown that immature dendritic cells (iDC) fuse faster and more efficiently than monocytes in forming OC-like multinucleated giant cells (MGCs), and that osteopontin (OPN) is involved in the pathogenesis of inflammatory bone diseases. In this study, we hypothesized that OPN is a key factor for generation of OC-like MGCs from iDCs. We used an in vitro culture system to differentiate iDCs, derived from monocytes obtained from the blood of healthy donors, into OC-like MGCs. We evaluated OPN levels and expression of OPN receptors during the course of differentiation. OPN has an arginine-glycine-aspartic acid (RGD) motif, and protease cleavage reveals a SVVYGLR motif. The concentrations of both full-length and cleaved forms of OPN increased during the course of OC-like MGC formation. Expression of OPN RGD- and SVVYGLR-recognizing receptors also increased at later stages. We analyzed whether blocking OPN binding to its receptors affected OC-like MGC formation. Monocytes treated with OPN siRNA were able to differentiate into iDCs effectively; however, differentiation of these iDCs into OC-like MGCs was significantly reduced. The formation of OC-like MGCs was not significantly reduced by RGD synthetic peptide. By contrast, SVVYGLR synthetic peptide caused a significant reduction. These data suggest that the cleaved form of OPN plays a critical role in driving iDC differentiation into OC-like MGCs in the early phase of differentiation, in an autocrine and/or paracrine fashion.}, } @article {pmid24128082, year = {2014}, author = {Verma, S and Dey, P}, title = {Correlation of morphological markers of chromosomal instability in fine needle aspiration cytology with grade of breast cancer.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {25}, number = {4}, pages = {259-263}, doi = {10.1111/cyt.12096}, pmid = {24128082}, issn = {1365-2303}, mesh = {*Biopsy, Fine-Needle ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma/*diagnosis/genetics/pathology ; Chromosomal Instability/genetics ; *Cytodiagnosis ; Female ; Humans ; Neoplasm Grading ; }, abstract = {OBJECTIVE: The aim of the present study was to investigate morphological markers of chromosomal instability (CI) in relation to cytological grade of breast cancer in fine needle aspiration cytology (FNAC) specimens.

METHODS: Herein we selected 55 cases of invasive ductal carcinoma diagnosed on FNAC. Representative haematoxylin and eosin (H&E)-stained smears were chosen to count chromatin bridges, multipolar mitoses per smear, and micronuclei and nuclear budding per 1000 carcinoma cells. The cases were also graded by two independent observers as grade I, II and III. The CI markers were correlated with the grade of breast carcinomas.

RESULTS: Out of 55 carcinomas, nine were grade I, nine grade II and 37 grade III. While none of the grade I carcinomas showed chromosomal bridges, the number per smear was 0.4 (± 0.7) and 3.1 (± 2.5) for grade II and III carcinomas, respectively. No multipolar mitoses were observed in grade I or II carcinomas; the number per smear was 3.7 (±3.0) in grade III carcinomas. The mean number per 1000 malignant cells of micronuclei was 1.2 (±1.7), 3.7 (±2.1) and 12.2 (±5.1) and of nuclear buds was 2.3 (±3.2), 4.7 (±2.1) and 12.4 (±4.7) in grade I, II and III carcinomas, respectively. There was a significant increase in the mean numbers of chromatin bridges, micronuclei and nuclear buds in grade I, II and III carcinomas (anova test; P < 0.001).

CONCLUSION: This is the first study of four morphological markers of CI in FNAC smears of breast cancer. This study establishes strong correlation of these markers with other criteria for cytological grading.}, } @article {pmid24125077, year = {2013}, author = {Kranz, AL and Jiao, CY and Winterkorn, LH and Albritton, SE and Kramer, M and Ercan, S}, title = {Genome-wide analysis of condensin binding in Caenorhabditis elegans.}, journal = {Genome biology}, volume = {14}, number = {10}, pages = {R112}, pmid = {24125077}, issn = {1474-760X}, support = {P40 OD010440/OD/NIH HHS/United States ; U01 HG0044270/HG/NHGRI NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/*metabolism ; Animals ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/*genetics/*metabolism ; Chromatin Immunoprecipitation ; Chromosomes/genetics/metabolism ; DNA-Binding Proteins/*genetics/*metabolism ; *Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Male ; Multiprotein Complexes/*genetics/*metabolism ; Mutation ; Nucleotide Motifs ; Position-Specific Scoring Matrices ; Promoter Regions, Genetic ; Protein Binding ; Reproducibility of Results ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {BACKGROUND: Condensins are multi-subunit protein complexes that are essential for chromosome condensation during mitosis and meiosis, and play key roles in transcription regulation during interphase. Metazoans contain two condensins, I and II, which perform different functions and localize to different chromosomal regions. Caenorhabditis elegans contains a third condensin, I(DC), that is targeted to and represses transcription of the X chromosome for dosage compensation.

RESULTS: To understand condensin binding and function, we performed ChIP-seq analysis of C. elegans condensins in mixed developmental stage embryos, which contain predominantly interphase nuclei. Condensins bind to a subset of active promoters, tRNA genes and putative enhancers. Expression analysis in kle-2-mutant larvae suggests that the primary effect of condensin II on transcription is repression. A DNA sequence motif, GCGC, is enriched at condensin II binding sites. A sequence extension of this core motif, AGGG, creates the condensin IDC motif. In addition to differences in recruitment that result in X-enrichment of condensin I(DC) and condensin II binding to all chromosomes, we provide evidence for a shared recruitment mechanism, as condensin I(DC) recruiter SDC-2 also recruits condensin II to the condensin I(DC) recruitment sites on the X. In addition, we found that condensin sites overlap extensively with the cohesin loader SCC-2, and that SDC-2 also recruits SCC-2 to the condensin I(DC) recruitment sites.

CONCLUSIONS: Our results provide the first genome-wide view of metazoan condensin II binding in interphase, define putative recruitment motifs, and illustrate shared loading mechanisms for condensin I(DC) and condensin II.}, } @article {pmid24123465, year = {2014}, author = {Kim, JH and Ryu, JK and Jahng, GH and Song, JY}, title = {Double inversion recovery MR imaging of the breast: efficacy in detection of breast cancer.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {39}, number = {1}, pages = {51-58}, doi = {10.1002/jmri.24115}, pmid = {24123465}, issn = {1522-2586}, mesh = {Adult ; Aged ; Biopsy ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Contrast Media/chemistry ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Regression Analysis ; Reproducibility of Results ; Retrospective Studies ; Signal-To-Noise Ratio ; }, abstract = {PURPOSE: To investigate the efficacy of the double inversion recovery sequence (DIR) in breast cancer detection.

MATERIALS AND METHODS: Fifty-six patients with biopsy-proven breast cancers underwent preoperative breast MRI, including sagittal DIR and contrast-enhanced T1-weighted images (CE-T1WI). Twenty-four of the 56 patients additionally underwent sagittal T1WI and T2WI. The signal intensities of the lesion (L) and ipsilateral normal breast tissue (N) were measured. The lesion-to-normal ratio (LNR) was defined as LNR = 100(L-N)/N. We compared LNRs among the four sequences, and then assessed the differences of LNRs between CE-T1WI and DIR in each pathologic subgroup (IDC and non-IDC group). Multiple regression analysis was performed to identify predictors of the signal-to-noise ratios (SNR) of the normal tissue or lesion and LNRs.

RESULTS: The mean LNR did not differ significantly between DIR (58.65 ± 71.55) and CE-T1WI (59.78 ±31.04), nor did the LNRs between DIR and CE-T1WI in the two subgroups. The LNRs of DIR did not differ significantly between the two subgroups (P = 0.247). The SNR of lesions in DIR was correlated with the intraductal component percentage (r(2) = 0.485, P = 0.037).

CONCLUSION: DIR and CE-T1WI showed similar tumor detection efficacy, and DIR could complement dynamic MRI for detecting breast cancer without a contrast agent.}, } @article {pmid24114530, year = {2014}, author = {Nakash, O and Nagar, M and Danilovich, E and Bentov-Gofrit, D and Lurie, I and Steiner, E and Sadeh-Sharvit, S and Szor, H and Levav, I}, title = {Ethnic disparities in mental health treatment gap in a community-based survey and in access to care in psychiatric clinics.}, journal = {The International journal of social psychiatry}, volume = {60}, number = {6}, pages = {575-583}, doi = {10.1177/0020764013504562}, pmid = {24114530}, issn = {1741-2854}, mesh = {Adult ; Ethnicity/*statistics & numerical data ; Female ; Health Care Surveys ; Health Services Accessibility/*statistics & numerical data ; Healthcare Disparities/*ethnology/statistics & numerical data ; Humans ; Israel/epidemiology ; Jews/ethnology/psychology/statistics & numerical data ; Male ; Mental Disorders/therapy ; Mental Health Services/*statistics & numerical data ; }, abstract = {BACKGROUND: Contrasting social status of ethnic groups differentially impacts the use of psychiatric services, including in Israel, despite its universal health system. However, relevant studies are limited.

AIMS: To examine ethnic differences in mental health treatment gap and in access to specialized care.

METHODS: Data were gathered from two sources. Study I included Mizrahi (Jews of North African/Asian origin, socially disadvantaged, n = 136) and Ashkenazi (Jews of European American origin, socially advantaged, n = 69) who were diagnosed with common mental disorders in the preceding 12 months in the Israeli component of the World Mental Health Survey. Study II included Mizrahi (n = 133) and Ashkenazi (n = 96) service users entering ambulatory mental health care.

RESULTS: Study I showed that the treatment gap was larger among Mizrahi compared with Ashkenazi respondents (28% standard error (SE) = 4.1 and 45% SE = 6.2, respectively, sought services) following adjustment for sociodemographic confounders (adjusted odds ratio (AOR) = 2.28, 95% confidence interval (CI) = 1.1-4.8). Study II showed that the access to specialized care lagged over a year among 40% of service users of both ethnic groups. No significant ethnic differences emerged in variables related to delay in accessing care.

CONCLUSIONS: Treatment gap was larger among ethnically disadvantaged compared with the advantaged group. However, once in treatment, service users of both ethnic groups report similar barriers to care.}, } @article {pmid24113788, year = {2013}, author = {Ganoth, A and Tsfadia, Y and Wiener, R}, title = {Ubiquitin: molecular modeling and simulations.}, journal = {Journal of molecular graphics & modelling}, volume = {46}, number = {}, pages = {29-40}, doi = {10.1016/j.jmgm.2013.09.006}, pmid = {24113788}, issn = {1873-4243}, mesh = {Humans ; *Molecular Dynamics Simulation ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/chemistry ; Ubiquitin/*chemistry ; Ubiquitin-Activating Enzymes/chemistry ; Ubiquitin-Conjugating Enzymes/chemistry ; Ubiquitin-Protein Ligases/chemistry ; Ubiquitination ; }, abstract = {The synthesis and destruction of proteins are imperative for maintaining their cellular homeostasis. In the 1970s, Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered that certain proteins are tagged by ubiquitin before degradation, a discovery that awarded them the 2004 Nobel Prize in Chemistry. Compelling data gathered during the last several decades show that ubiquitin plays a vital role not only in protein degradation but also in many cellular functions including DNA repair processes, cell cycle regulation, cell growth, immune system functionality, hormone-mediated signaling in plants, vesicular trafficking pathways, regulation of histone modification and viral budding. Due to the involvement of ubiquitin in such a large number of diverse cellular processes, flaws and impairments in the ubiquitin system were found to be linked to cancer, neurodegenerative diseases, genetic disorders, and immunological disorders. Hence, deciphering the dynamics and complexity of the ubiquitin system is of significant importance. In addition to experimental techniques, computational methodologies have been gaining increasing influence in protein research and are used to uncover the structure, stability, folding, mechanism of action and interactions of proteins. Notably, molecular modeling and molecular dynamics simulations have become powerful tools that bridge the gap between structure and function while providing dynamic insights and illustrating essential mechanistic characteristics. In this study, we present an overview of molecular modeling and simulations of ubiquitin and the ubiquitin system, evaluate the status of the field, and offer our perspective on future progress in this area of research.}, } @article {pmid24111705, year = {2014}, author = {Buchanan, J and Beckmann, M}, title = {Postpartum voiding dysfunction: identifying the risk factors.}, journal = {The Australian & New Zealand journal of obstetrics & gynaecology}, volume = {54}, number = {1}, pages = {41-45}, doi = {10.1111/ajo.12130}, pmid = {24111705}, issn = {1479-828X}, mesh = {Adult ; Cesarean Section/adverse effects ; Female ; Humans ; Incidence ; Labor, Obstetric ; Organ Size ; Postpartum Period ; Pregnancy ; Puerperal Disorders/*etiology ; Retrospective Studies ; Risk Factors ; Urinary Bladder/anatomy & histology ; Urinary Retention/epidemiology/*etiology ; Urine ; }, abstract = {BACKGROUND: Postpartum urinary retention (PPUR) (also known as voiding dysfunction) is a common problem, defined as the inability to completely void after giving birth. If voiding dysfunction is not recognised, bladder overdistension can lead to denervation, detrusor atony and prolonged voiding dysfunction.

AIM: To describe the incidence of PPUR amongst postpartum women undergoing routine bladder scanning and to identify the factors that lead to postpartum voiding dysfunction.

METHODS: A retrospective analysis of all postpartum women at Mater Health Services, Brisbane between February and December 2012 was undertaken. Routinely collected postvoid residual bladder volumes (PVRBV) were reported using a bladder scanner at four and six hours and two to three days postbirth or following removal of an indwelling catheter (IDC). The characteristics of women with or without increased PVRBV were analysed.

RESULTS: Postvoid residual bladder volumes at four-hours postbirth/removal of IDC were available for 5558 women of whom 281 (5.1%) had a residual volume measured >150 mL. Obstetric factors explored included mode of birth, method of analgesia or anaesthesia, duration of labour, degree of perineal trauma, birth weight, gestation, parity, maternal age and body mass index. After controlling for confounders, nulliparity (aOR 1.53; 95% CI 1.05-2.26), birth by caesarean section (aOR 2.21; 95% CI 1.10-4.41) and 3rd/4th degree perineal trauma (aOR 2.01; 95% CI 1.09-3.72) were significant independent predictors of PPUR.

CONCLUSION: Following the introduction of a protocol of timed voiding and routine measurement of PVRBV after birth/removal of IDC, PPUR is uncommon. Adopting a risk-factor-based approach to PVRBV screening is not supported by these data.}, } @article {pmid24106833, year = {2013}, author = {Shaheed, SU and Rustogi, N and Scally, A and Wilson, J and Thygesen, H and Loizidou, MA and Hadjisavvas, A and Hanby, A and Speirs, V and Loadman, P and Linforth, R and Kyriacou, K and Sutton, CW}, title = {Identification of stage-specific breast markers using quantitative proteomics.}, journal = {Journal of proteome research}, volume = {12}, number = {12}, pages = {5696-5708}, doi = {10.1021/pr400662k}, pmid = {24106833}, issn = {1535-3907}, mesh = {Adult ; Aged ; Amine Oxidase (Copper-Containing)/genetics/isolation & purification/metabolism ; Biological Transport ; Biomarkers, Tumor/*genetics/isolation & purification/metabolism ; Breast Neoplasms/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/metabolism/pathology ; Case-Control Studies ; Cofilin 1/*genetics/isolation & purification/metabolism ; Female ; Fibroadenoma/diagnosis/*genetics/metabolism/pathology ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Lipid Metabolism ; Middle Aged ; Neoplasm Staging ; Oxidation-Reduction ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Proteolysis ; Proteomics ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Tissue Array Analysis ; Tumor Protein, Translationally-Controlled 1 ; }, abstract = {Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.}, } @article {pmid24103354, year = {2013}, author = {Kim, TY and Kim, SH and Kang, BJ and Kim, HS and Cha, ES and Kim, JY and Song, BJ}, title = {Characterization of the enhancing lesions on dynamic contrast enhanced magnetic resonance imaging in patients with interstitial mammoplasty.}, journal = {European journal of radiology}, volume = {82}, number = {12}, pages = {2205-2211}, doi = {10.1016/j.ejrad.2013.09.008}, pmid = {24103354}, issn = {1872-7727}, mesh = {Adult ; Aged ; Breast Neoplasms/*etiology/*pathology ; Contrast Media ; Female ; Foreign-Body Reaction/*etiology/*pathology ; *Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Mammaplasty/*adverse effects ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {PURPOSE: The purpose of this study was to categorize the morphologic and kinetic features of enhancing lesions in breasts with interstitial mammoplasty using dynamic contrast-enhanced magnetic resonance imaging and to assess factors predictive of breast cancer.

MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiological data of 21 enhancing lesions in 19 patients with interstitial mammoplasty, who underwent breast magnetic resonance imaging and biopsy or an operation in our hospital from September 2008 to July 2012. These lesions were sorted by morphological and kinetic features and final assessment category according to the BI-RADS lexicon.

RESULTS: Nine cases were confirmed to be ductal carcinoma in situ (n = 2) and invasive ductal carcinoma (n = 7), and the remaining 12 cases were fibrocystic disease (n = 2), fibroadenoma (n = 2), fat necrosis (n = 1), foreign body granuloma (n = 3) and silicone mastitis (n = 1). Common features of malignancy included irregular shape (50.0%), spiculated margins (75.0%), heterogeneous enhancement (50.0%) and type III kinetic pattern (87.5%). The correlations of margins and kinetic curve pattern with benignity and malignancy approached statistical significance (p = 0.02, respectively). We found no correlation for shape (p = 0.33) or internal enhancement (p = 0.42) between lesion types. The malignancy rate of enhancing lesions was 42.8% (9/21). The sensitivity and specificity of dynamic contrast-enhanced magnetic resonance imaging were 100% and 16.67%, respectively. The positive predictive value, negative predictive value and accuracy of magnetic resonance imaging were 47.38%, 100% and 52.38%. Overall inter-observer agreement for the kinetic curve pattern was good (κ = 0.67). Moderate agreement was seen in describing the shape, margin, enhancement and assessing the final category (κ = 0.59, 0.46, 0.58 and 0.49, respectively).

CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging had a high sensitivity, negative predictive value for the prediction of breast cancer but a low specificity due to features of foreign body-related lesions that mimicked malignant lesions. The significant predictive factors for malignancy were margins, kinetic curve pattern and final assessment category. Overall inter-observer agreement for the kinetic curve pattern was good.}, } @article {pmid24100125, year = {2014}, author = {Ben-David, BM and Tewari, A and Shakuf, V and Van Lieshout, PH}, title = {Stroop effects in Alzheimer's disease: selective attention speed of processing, or color-naming? A meta-analysis.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {38}, number = {4}, pages = {923-938}, doi = {10.3233/JAD-131244}, pmid = {24100125}, issn = {1875-8908}, mesh = {Alzheimer Disease/*diagnosis/*psychology ; Attention/*physiology ; Color Perception/*physiology ; Humans ; Reaction Time/*physiology ; *Stroop Test ; }, abstract = {Selective attention, an essential part of daily activity, is often impaired in people with Alzheimer's disease (AD). Usually, it is measured by the color-word Stroop test. However, there is no universal agreement whether performance on the Stroop task changes significantly in AD patients; or if so, whether an increase in Stroop effects reflects a decrease in selective attention, a slowing in generalized speed of processing (SOP), or is the result of degraded color-vision. The current study investigated the impact of AD on Stroop performance and its potential sources in a meta-analysis and mathematical modeling of 18 studies, comparing 637 AD patients with 977 healthy age-matched participants. We found a significant increase in Stroop effects for AD patients, across studies. This AD-related change was associated with a slowing in SOP. However, after correcting for a bias in the distribution of latencies, SOP could only explain a moderate portion of the total variance (25%). Moreover, we found strong evidence for an AD-related increase in the latency difference between naming the font-color and reading color-neutral stimuli (r2 = 0.98). This increase in the dimensional imbalance between color-naming and word-reading was found to explain a significant portion of the AD-related increase in Stroop effects (r2 = 0.87), hinting on a possible sensory source. In conclusion, our analysis highlights the importance of controlling for sensory degradation and SOP when testing cognitive performance and, specifically, selective attention in AD patients. We also suggest possible measures and tools to better test for selective attention in AD.}, } @article {pmid24099815, year = {2013}, author = {Gudadze, M and Kankava, K and Mariamidze, A and Mosidze, T and Burkadze, G}, title = {Distribution of CD44/CD24 positive cells in ductal invasive carcinoma of breast of different grade and molecular subtype.}, journal = {Georgian medical news}, volume = {}, number = {222}, pages = {50-57}, pmid = {24099815}, issn = {1512-0112}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/metabolism/pathology ; CD24 Antigen/immunology/*metabolism ; Carcinoma, Ductal, Breast/metabolism/pathology ; Female ; Humans ; Hyaluronan Receptors/immunology/*metabolism ; *Immunity, Cellular ; Immunohistochemistry ; Middle Aged ; *Neoplasm Staging ; Neoplastic Stem Cells/*immunology/metabolism/pathology ; Retrospective Studies ; Young Adult ; }, abstract = {The purpose of our study was to learn the distribution characteristics of cancer stem cell markers (CD24, CD44) in invasive carcinomas with different grade and molecular subtype. For research was used 1324 postoperative breast cancer samples, from which were selected 393 patient with invasive ductal carcinoma samples examined 2008-2012 in Laboratory of "Pathgeo Union of Pathologist" is and N.Kipshidze Central University Hospital. The age range is between 23-73 year. For all cases were performed immunohistochemical study using ER, PR, Her2, Ki67, CK5- molecular markers (Leica Microsystems). For identify cancer stem cells mononuclear antibodies CD24 (BIOCARE MEDICAL, CD44 - Clone 156-3C11; CD24 - Clone SN3b) were used. Association of CD44/CD24 expression in different subtypes of cells, between clinicopathological parameters and different biological characteristics were performed by Pearson correlation and usind X2 tests. Obtained quantitative statistical analyses were performed by using SPSS V.19.0 program. Statistically significant were considered 95% of confidence interval. The data shows, that towards G1-G3, amount of CD44 positive cases increased twice. CD44 positive cases are evenly distributed between Luminal A, Luminal B, HER2+, triple negative basal like cell subtypes and in significantly less (4,8 times) in Her2+ cases. Maximum amount of CD44 negative cases is shown in Luminal A subtype, which could be possible cause of better prognosis and high sensitivity for chemotherapy. For one's part such aggressive subtypes of breast cancer as Luminal B and basal like cell type, are characterized by CD44 positive and antigen high expression, which can be reason of aggressive nature of this types and also reason of chemotherapy resistance. As well as amount of CD24 positive cases according to malignancy degree, also antigen expression features does not show any type of correlation between malignancy degree and CD24 positivity or with CD24 expression features, or presence of stem cells. That can be the reason of tumor aggressivity and chemoresistance. exceptions are Her2 positive tumors because they have different base of carcinogenesis.}, } @article {pmid24099564, year = {2013}, author = {Noël, S and Massart, L and Hamaide, A}, title = {Urodynamic investigation by telemetry in Beagle dogs: validation and effects of oral administration of current urological drugs: a pilot study.}, journal = {BMC veterinary research}, volume = {9}, number = {}, pages = {197}, pmid = {24099564}, issn = {1746-6148}, mesh = {Administration, Oral ; Animals ; Dogs/*physiology ; Female ; Monitoring, Physiologic/instrumentation/methods/*veterinary ; Pilot Projects ; Telemetry ; Urination/drug effects/*physiology ; Urodynamics/*physiology ; Urological Agents/administration & dosage/*pharmacology ; }, abstract = {BACKGROUND: Vesico-urethral function may be evaluated in humans and dogs by conventional urodynamic testing (cystometry and urethral pressure profilometry) or by electromyography. These techniques are performed under general anaesthesia in dogs. However, anaesthesia can depress bladder and urethral pressures and inhibit the micturition reflex. The primary objective of this pilot study was to evaluate the use of telemetry for urodynamic investigation in dogs. We also aimed to determine the applicability of telemetry to toxicologic studies by assessing the repeatability of telemetric recordings.

RESULTS: Conventional diuresis cystometry was performed in six continent adult female Beagle dogs prior to surgical implantation of telemetric and electromyographic devices. In the first phase of the telemetric study, continuous recordings were performed over 8 days and nights. Abdominal, intravesical and detrusor threshold pressures (Pdet th), voided volume (Vv), urethral smooth muscle electrical activity and involuntary detrusor contractions (IDC) were measured during the bladder filling phase and during micturition episodes.Vv recorded during telemetry was significantly lower than bladder volume obtained by diuresis cystometry. Repeatability of telemetric measurements was greater for observations recorded at night. IDC frequency and Pdet th were both lower and Vv was higher at night compared to values recorded during daytime.In the second phase of the telemetric study, phenylpropanolamine, oestriol, bethanechol, oxybutynin or duloxetine were administered orally for 15 days. For each drug, continuous recordings were performed overnight for 12 hours on days 0, 1, 8 and 15. Electromyographic urethral activity was significantly increased 8 days after oestriol or duloxetine administration. No significant changes in bladder function were observed at any time point.

CONCLUSIONS: In dogs, the high repeatability of nocturnal telemetric recordings indicates that this technique could provide more informative results for urologic research. Urethral smooth muscle electrical activity appears to be modified by administration of drugs with urethral tropism. In this pilot telemetric study, bladder function was not affected by oral administration of urological drugs at their recommended clinical dosages. Experimental studies, (pharmacokinetic and pharmacodynamic) and clinical studies are warranted to further define the effects of these drugs on vesico-urethral function in dogs.}, } @article {pmid24096585, year = {2014}, author = {Zhou, J and Mao, XY and Wang, X and Ai, T and Ma, JJ and Li, YH}, title = {Anti-anaemia efficacy of β-lactoglobulin hydrolysate-iron complex on iron-deficient anaemic rats.}, journal = {European journal of nutrition}, volume = {53}, number = {3}, pages = {877-884}, pmid = {24096585}, issn = {1436-6215}, mesh = {Anemia, Iron-Deficiency/blood/*diet therapy/metabolism ; Animals ; Cytokines/antagonists & inhibitors/blood/metabolism ; *Dietary Supplements ; Female ; Ferritins/agonists/blood ; Hematinics/administration & dosage/chemistry/*therapeutic use ; Hemoglobins/agonists/analysis ; Iron/analysis ; Iron Chelating Agents/administration & dosage/chemistry/*therapeutic use ; Iron, Dietary/administration & dosage/*therapeutic use ; Lactoglobulins/administration & dosage/chemistry/*therapeutic use ; Liver/chemistry/enzymology ; Malondialdehyde/antagonists & inhibitors/blood/metabolism ; Oxidative Stress ; Oxidoreductases/blood/metabolism ; Protein Hydrolysates/administration & dosage/chemistry/*therapeutic use ; Random Allocation ; Rats, Sprague-Dawley ; Weaning ; }, abstract = {PURPOSE: The effects of orally administered β-lactoglobulin hydrolysate-iron complex (β-LGH-Fe) on haematological and biochemical parameters in anaemic rats were evaluated. Female weaning Sprague-Dawley rats were fed with iron-deficient diet to induce iron deficiency anaemia. After 6 weeks, the obtained anaemic rats were divided into five groups: iron deficiency control group (iron-deficient diet without β-LGH-Fe complex supplementation, IDC); three groups supplemented with different dosages of β-LGH-Fe complex (0.5 mg Fe/kg BW, iron-deficient diet with low β-LGH-Fe, IDLFe; 2.0 mg Fe/kg BW, iron-deficient diet with medium β-LGH-Fe, IDMF; 4.0 mg Fe/kg BW, iron-deficient diet with high β-LGH-Fe, IDHFe); and ferrous sulphate-supplemented group at a dosage of 2.0 mg Fe/kg BW.

RESULTS: β-LGH-Fe complex could significantly improve hematocrit and haemoglobin decrease, and normalise the serum iron level, total iron-binding capacity and transferrin saturation of anaemic rats in a dose-dependent manner. Serum ferritin content and hepatic nonheme iron level were also increased. In addition, the antioxidant enzyme activities of superoxidase dismutase, catalase and glutathione peroxidase in both plasma and liver homogenate were improved. The production of malondialdehyde and pro-inflammatory cytokines (TNF-α and IL-6) decreased.

CONCLUSIONS: It suggests that β-LGH-Fe complex can ameliorate iron deficiency anaemia, which might make it a potential ingredient with anti-anaemia activity.}, } @article {pmid24096546, year = {2014}, author = {Xiao, Y and Zhang, S and Hou, G and Zhang, X and Hao, X and Zhang, J}, title = {Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {35}, number = {3}, pages = {2035-2045}, pmid = {24096546}, issn = {1423-0380}, mesh = {Adult ; Aged ; Breast Neoplasms/*complications/*mortality/*pathology ; Diabetes Mellitus, Type 2/*complications/*mortality/*pathology ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Kaplan-Meier Estimate ; Metformin/therapeutic use ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002); 93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer.}, } @article {pmid24091078, year = {2013}, author = {Kurul, S and Akgun, Z and Saglam, EK and Basaran, M and Yucel, S and Tuzlali, S}, title = {Successful treatment of triple primary tumor.}, journal = {International journal of surgery case reports}, volume = {4}, number = {11}, pages = {1013-1016}, pmid = {24091078}, issn = {2210-2612}, abstract = {INTRODUCTION: The occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin.

PRESENTATION OF CASE: A 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression.

DISCUSSION: The patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging.

CONCLUSION: This is a very rare synchronous triple tumor case.}, } @article {pmid24090706, year = {2013}, author = {Cleary, M and Trefz, F and Muntau, AC and Feillet, F and van Spronsen, FJ and Burlina, A and Bélanger-Quintana, A and Giżewska, M and Gasteyger, C and Bettiol, E and Blau, N and MacDonald, A}, title = {Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes.}, journal = {Molecular genetics and metabolism}, volume = {110}, number = {4}, pages = {418-423}, doi = {10.1016/j.ymgme.2013.09.001}, pmid = {24090706}, issn = {1096-7206}, mesh = {Adult ; Age Factors ; Biopterin/*analogs & derivatives/therapeutic use ; Diet ; Humans ; Phenylalanine/*blood/*genetics/metabolism ; Phenylalanine Hydroxylase/genetics/metabolism ; Phenylketonurias/*blood/drug therapy/genetics/physiopathology ; PubMed ; }, abstract = {Fluctuations in blood phenylalanine concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine concentrations affects outcomes, particularly neurocognitive outcome. Electronic literature searches of Embase and PubMed were performed for English-language publications, and the bibliographies of identified publications were also searched. In patients with PKU, phenylalanine concentrations are highest in the morning. Factors that can affect phenylalanine fluctuations include age, diet, timing and dosing of protein substitute and energy intake, dietary adherence, phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and protein metabolism, illness, and growth rate. Even distribution of phenylalanine-free protein substitute intake throughout 24h may reduce blood phenylalanine fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem to have less fluctuation in their blood phenylalanine concentrations than controls. An increase in blood phenylalanine concentration may result in increased brain and cerebrospinal fluid phenylalanine concentrations within hours. Although some evidence suggests that stabilization of blood phenylalanine concentrations may have benefits in patients with PKU, more studies are needed to distinguish the effects of blood phenylalanine fluctuations from those of poor metabolic control.}, } @article {pmid24086515, year = {2013}, author = {He, W and Tong, Y and Wang, Y and Liu, J and Luo, G and Wu, J and Zhang, J}, title = {Serum soluble CD14 is a potential prognostic indicator of recurrence of human breast invasive ductal carcinoma with Her2-enriched subtype.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e75366}, pmid = {24086515}, issn = {1932-6203}, mesh = {Area Under Curve ; Biomarkers, Tumor/*blood ; Breast Neoplasms/blood/*epidemiology ; Carcinoma, Ductal, Breast/blood/*epidemiology ; Female ; Humans ; Lipopolysaccharide Receptors/*blood ; Neoplasm Recurrence, Local/blood/*epidemiology ; Proteomics/methods ; ROC Curve ; Receptor, ErbB-2/genetics/*metabolism ; Risk Factors ; }, abstract = {In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.}, } @article {pmid24085500, year = {2014}, author = {Kalinyak, JE and Berg, WA and Schilling, K and Madsen, KS and Narayanan, D and Tartar, M}, title = {Breast cancer detection using high-resolution breast PET compared to whole-body PET or PET/CT.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {41}, number = {2}, pages = {260-275}, pmid = {24085500}, issn = {1619-7089}, support = {5 R44 CA103102-05/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging ; Carcinoma/*diagnostic imaging ; Female ; Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Radiopharmaceuticals ; *Tomography, X-Ray Computed ; *Whole Body Imaging ; }, abstract = {PURPOSE: To compare the performance characteristics of positron emission mammography (PEM) with those of whole-body PET (WBPET) and PET/CT in women with newly diagnosed breast cancer.

METHODS: A total of 178 women consented to PEM for presurgical planning in an IRB-approved protocol and also underwent either WBPET (n = 69) or PET/CT (n = 109) imaging, as per usual care at three centers. Tumor detection sensitivity, positive predictive values, and (18)F-fluorodeoxyglucose (FDG) uptake were compared between the modalities. The effects of tumor size, type, and grade on detection were examined. The chi-squared or Fisher's exact tests were used to compare distributions between groups, and McNemar's test was used to compare distributions for paired data within subject groups, i.e. PEM versus WBPET or PEM versus PET/CT.

RESULTS: The mean age of the women was 59 ± 12 years (median 60 years, range 26-89 years), with a mean invasive index tumor size of 1.6 ± 0.8 cm (median 1.5 cm, range 0.5-4.0 cm). PEM detected more index tumors (61/66, 92%) than WBPET (37/66, 56%; p < 0.001) or PET/CT (95/109, 87% vs. 104/109, 95% for PEM; p < 0.029). Sensitivity for the detection of additional ipsilateral malignancies was also greater with PEM (7/15, 47%) than with WBPET (1/15, 6.7%; p = 0.014) or PET/CT (3/23, 13% vs. 13/23, 57% for PEM; p = 0.003). Index tumor detection decreased with decreasing invasive tumor size for both WBPET (p = 0.002) and PET/CT (p < 0.001); PEM was not significantly affected (p = 0.20). FDG uptake, quantified in terms of maximum PEM uptake value, was lowest in ductal carcinoma in situ (median 1.5, range 0.7-3.0) and invasive lobular carcinoma (median 1.5, range 0.7-3.4), and highest in grade III invasive ductal carcinoma (median 3.1, range 1.4-12.9).

CONCLUSION: PEM was more sensitive than either WBPET or PET/CT in showing index and additional ipsilateral breast tumors and remained highly sensitive for tumors smaller than 1 cm.}, } @article {pmid24080478, year = {2014}, author = {Nakiwogga-Muwanga, A and Alamo-Talisuna, S and Musaazi, J and Kambugu, A and Ssekawungu, P and Katabira, E and Colebunders, R}, title = {Inadequate monitoring in advanced stages of disease with lack of supportive counseling increases attrition among patients on antiretroviral treatment at a large urban clinic in Uganda.}, journal = {Journal of the International Association of Providers of AIDS Care}, volume = {13}, number = {6}, pages = {547-554}, doi = {10.1177/2325957413501719}, pmid = {24080478}, issn = {2325-9574}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-Retroviral Agents/*therapeutic use ; Case-Control Studies ; *Directive Counseling ; Female ; HIV Infections/*diagnosis/psychology/*therapy ; Humans ; Lost to Follow-Up ; Male ; Patient Compliance ; Risk Factors ; *Social Support ; Uganda ; *Urban Health Services ; }, abstract = {BACKGROUND: The purpose of this case-control study was to identify risk factors for loss to follow-up (LTFU).

METHODS: Cases and controls were selected from HIV-positive patients, aged 18 years and older, on antiretroviral therapy (ART) at the Infectious Diseases Clinic (IDC) in January 2008. As cases, we selected 209 patients who in 2008 did not return to the clinic within 90 days of their scheduled appointment date. As controls, we randomly selected 626 patients from the 5872 patients who were following up at the end of December 2008.

RESULTS: In multivariable logistic regression analysis, urban or semiurban residence, World Health Organization disease stage III or IV at ART initiation, a median CD4 count at last visit <200 cells/mm(3), tuberculosis (TB) in the 6 months before the last visit, absence of counseling before ART initiation, and no disclosure of HIV status were associated with LTFU.

CONCLUSION: This study demonstrates the importance of close patient monitoring in advanced stages of disease, supportive counseling for patients initiating ART, extra psychosocial support for patients with TB and HIV coinfection, assisting patients with disclosure, and setting up a good referral system to retain patients on ART.}, } @article {pmid24078229, year = {2014}, author = {Saito, R and Miki, Y and Hata, S and Takagi, K and Iida, S and Oba, Y and Ono, K and Ishida, T and Suzuki, T and Ohuchi, N and Sasano, H}, title = {Aryl hydrocarbon receptor in breast cancer—a newly defined prognostic marker.}, journal = {Hormones & cancer}, volume = {5}, number = {1}, pages = {11-21}, pmid = {24078229}, issn = {1868-8500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/drug therapy ; Carcinoma, Ductal/*diagnosis/drug therapy ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Estrogens/metabolism ; Female ; Humans ; Immunohistochemistry ; MCF-7 Cells ; Matrix Metalloproteinases/*metabolism ; Middle Aged ; Polychlorinated Dibenzodioxins/pharmacology ; Prognosis ; Protein Array Analysis ; Receptors, Aryl Hydrocarbon/agonists/*metabolism ; Signal Transduction ; }, abstract = {Aryl hydrocarbon receptor (AhR) has been reported to exert various anticancer effects upon breast carcinoma cells in vitro but its details have remained largely unknown. Therefore, we first examined the AhR status in 90 invasive ductal carcinoma patients using immunohistochemistry. We then performed in vitro studies including wound healing assay, invasion assay, and matrix metalloproteinase (MMP) protein array in order to further elucidate the roles of AhR signaling in breast carcinoma. The status of AhR immunoreactivity was inversely correlated with histological grade (P = 0.0135) and Ki-67 labeling index (LI; P = 0.0087) of the patients. In addition, results of both uni- and multivariate analyses revealed that AhR in carcinoma cells turned out an independent prognostic factor with a protective relative risk (P = 0.0179). An administration of 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR, significantly decreased Ki-67 LI in an AhR-dependent fashion in MCF-7, T47D, ZR75-1, and MDA-MB-231. Wound healing and invasion assays performed in T47D and ZR75-1 further demonstrated that 10 nM TCDD inhibited estrogen-induced migration and invasion of cells. MMP proteins associated with AhR in breast carcinoma cells were also firstly identified. These results demonstrated that AhR in breast carcinoma cells is considered a newly defined histological prognostic parameter of the breast cancer patients and effects of AhR activation on proliferation and MMPs expression may be related to the relatively good clinical outcome of AhR-positive breast cancer patients.}, } @article {pmid24076565, year = {2013}, author = {Tsushimi, T and Mori, H and Harada, T and Ikeda, Y and Ohnishi, H}, title = {Invasive micropapillary carcinoma of the breast in a male patient: Report of a case.}, journal = {International journal of surgery case reports}, volume = {4}, number = {11}, pages = {988-991}, pmid = {24076565}, issn = {2210-2612}, abstract = {INTRODUCTION: We report a rare case of invasive micropapillary carcinoma in the male breast.

PRESENTATION OF CASE: A 63-year-old man was referred to our hospital for investigation of a left breast tumor, which could be palpated in the upper lateral quadrant of the left nipple-areola complex. The tumor invaded the areola skin. Ultrasonography showed a 14.8×15.0×12.4mm low echoic mass, with an irregular lobulated border. Core needle biopsy indicated invasive ductal carcinoma, but the subtype could not be accurately determined. Mastectomy with axillary lymph node dissection was performed. Pathological examination indicated invasive micropapillary carcinoma, no lymph node metastasis, and a nuclear grade of 2. Immunohistochemical examination showed positive staining for estrogen and progesterone receptors, but negative staining for HER2. The Ki67 index was 5%. Tamoxifen was administered, and recurrence has not been noted for 1 year.

DISCUSSION: Women's IMPC generally shows a high HER2 positivity rate. However, HER2 positivity was noted in only 1 male patient with IMPC (14%) according to our literature review. Furthermore, in all cases of the mixed type that were reviewed, IMPC was associated with papillotubular carcinoma. These findings may be specific to IMPC in male patients.

CONCLUSION: IMPC is associated with a high rate of lymph node metastasis or recurrence and advanced vessel invasion, aggressive adjuvant chemotherapy following surgical resection should be selected for patients with IMPC.}, } @article {pmid24071019, year = {2013}, author = {Shatat, L and Gloyeske, N and Madan, R and O'Neil, M and Tawfik, O and Fan, F}, title = {Microinvasive breast carcinoma carries an excellent prognosis regardless of the tumor characteristics.}, journal = {Human pathology}, volume = {44}, number = {12}, pages = {2684-2689}, doi = {10.1016/j.humpath.2013.07.010}, pmid = {24071019}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; }, abstract = {The clinical implication of microinvasive breast carcinoma (MIBC), especially when multiple foci are identified, is still not clearly defined. This study is designed to collect clinicopathologic and follow up data on patients with MIBC. Histologic data including invasive breast cancer type, nuclear grade, number of microinvasive foci and lymph node status, as well as associated in situ component histologic and biomarkers parameters were recorded. Clinical follow-up data, such as local recurrence, distant metastasis and survival was also noted. Forty MIBC cases were identified among 1180 invasive breast cancer cases between 1998 and 2012, representing 3.4% of the overall invasive cases. The majority of the cases (28/40) had three or less foci of microinvasion and had high nuclear grade (26/40). The associated carcinoma in situ was also mostly high grade. The biomarker expression for estrogen receptor/human epidermal growth factor receptor 2 (ER/HER2) of the in situ component was heterogeneous. Of the 35 cases with known nodal status, 1 had macrometastasis, 1 had micrometastasis, 3 had isolated tumor cells, and the remaining had negative nodes. In the follow-up period (mean 30 months, median 15 months) none of the patients had recurrence, distant metastasis or died of disease. In conclusion, MIBC represents a small portion of invasive carcinomas. The majority of cases have high nuclear grade and are associated with high grade ductal carcinoma in situ. The latter doesn't show consistent ER/HER2 expression. Overall, the number of microinvasive foci, the extent and biomarker expression of the in situ component do not appear to impact the overall excellent outcome.}, } @article {pmid24065215, year = {2013}, author = {Pula, B and Olbromski, M and Wojnar, A and Gomulkiewicz, A and Witkiewicz, W and Ugorski, M and Dziegiel, P and Podhorska-Okolow, M}, title = {Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma.}, journal = {Cellular oncology (Dordrecht)}, volume = {36}, number = {6}, pages = {469-483}, pmid = {24065215}, issn = {2211-3436}, mesh = {Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Vessels/metabolism ; MCF-7 Cells ; Microvessels/metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SOXF Transcription Factors/*biosynthesis/blood/genetics/metabolism ; Vascular Endothelial Growth Factor D/genetics/metabolism ; }, abstract = {PURPOSE: SOX18 is a transcription factor known to be involved in hair follicle, blood and lymphatic vessel development, as well as wound healing processes (together with SOX7 and SOX17). In addition, it has been reported that SOX18 may affect the growth of cancer cells in vitro. Until now, the exact role of SOX18 expression in invasive ductal breast carcinoma (IDC) has remained unknown.

METHODS: In this study, we have investigated SOX18 expression in cancer cells and endothelial cells in 122 IDC samples using immunohistochemistry (IHC). SOX18 expression was also determined using real-time PCR and Western blotting in a series of breast cancer-derived cell lines (i.e., MCF-7, BT-474, SK-BR-3, MDA-MB-231, BO2).

RESULTS: Using IHC, we observed SOX18 nuclear expression in cancer cells, as well as in blood and lymphatic vessels of the IDC samples tested. SOX18 expression in the IDC samples correlated with a higher malignancy grade (Grade 2 and Grade 3 versus Grade 1; p = 0.02 and p = 0.009, respectively) and VEGF-D expression (r = 0.27, p = 0.007). SOX18 expression was also associated with HER2 positivity (p = 0.02). A significantly higher SOX18 expression was found in the HER2-positive cell line BT-474, and a significantly lower expression in the triple negative cell lines MDA-MB-231 and BO2. Laser capture microdissection of IDC samples revealed significantly higher mRNA SOX7, SOX17 and SOX18 expression levels in the vessels as compared to the cancer cells (p = 0.02 and p = 0.0002, p < 0.0001, respectively). SOX18 positive intratumoral and peritumoral microvessel counts (MVC) were associated with higher malignancy grades (p = 0.04 and p = 0.02, respectively). Moreover, peritumoral SOX18 positive MVC were found to act as an independent marker for a poor prognosis (p = 0.04).

CONCLUSION: SOX18 expression may serve as a marker for a poor prognosis in IDC.}, } @article {pmid24063566, year = {2013}, author = {Levit-Binnun, N and Davidovitch, M and Golland, Y}, title = {Sensory and motor secondary symptoms as indicators of brain vulnerability.}, journal = {Journal of neurodevelopmental disorders}, volume = {5}, number = {1}, pages = {26}, pmid = {24063566}, issn = {1866-1947}, abstract = {In addition to the primary symptoms that distinguish one disorder from the next, clinicians have identified, yet largely overlooked, another set of symptoms that appear across many disorders, termed secondary symptoms. In the emerging era of systems neuroscience, which highlights that many disorders share common deficits in global network features, the nonspecific nature of secondary symptoms should attract attention. Herein we provide a scholarly review of the literature on a subset of secondary symptoms--sensory and motor. We demonstrate that their pattern of appearance--across a wide range of psychopathologies, much before the full-blown disorder appears, and in healthy individuals who display a variety of negative symptoms--resembles the pattern of appearance of network abnormalities. We propose that sensory and motor secondary symptoms can be important indicators of underlying network aberrations and thus of vulnerable brain states putting individuals at risk for psychopathology following extreme circumstances.}, } @article {pmid24063181, year = {2013}, author = {Chen, J and Lü, Q and Wang, X and Li, H and Chen, Y and Yang, X and Zeng, H}, title = {[Breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy for breast cancer].}, journal = {Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery}, volume = {27}, number = {7}, pages = {872-875}, pmid = {24063181}, issn = {1002-1892}, mesh = {Adult ; Breast Implants ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Female ; Humans ; Mammaplasty/instrumentation/*methods ; Mastectomy/instrumentation/*methods ; Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Staging ; Nipples/surgery ; Patient Satisfaction ; Postoperative Complications/epidemiology/therapy ; Retrospective Studies ; Skin ; Tissue Expansion Devices ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the feasibility, oncological safety, and aesthetic result of skin-spring mastectomy (SSM) or nipple-spring mastectomy (NSM) in breast reconstruction of implant (permanent gel or expander) for breast cancer patients who were not fit for the breast conserving surgery (BCS).

METHODS: Between October 2005 and July 2011, 89 women with breast caner underwent SSM or NSM, with an average age of 42.4 years (range, 19-55 years) and an average disease duration of 5.7 months (range, 1-24 months). The pathological examination revealed invasive ductal carcinoma in 55 cases, ductal carcinoma in situ (DCIS) in 15 cases, invasive ductal carcinoma + DCIS in 8 cases, DCIS with infiltration in 10 cases, and occult breast cancer in 1 case. According to tumor staging criterion of American Joint Committee on Cancer (AJCC), 15 cases were rated as stage 0, 51 cases as stage I, 22 cases as stage II, and 1 case as unclear. Finally, 33 patients underwent SSM and 56 patients underwent NSM according to the location and diameter of tumor and the infiltration of tumor to nipple. Secondary breast reconstruction was performed with permanent gel replacement after axillary lymph node dissection in 9 patients with positive sentinel lymph node and 1 patient with occult breast cancer; immediate breast reconstruction was performed with permanent gel in the other patients. All the patients received the chemotherapy or/and radiotherapy according to the National Comprehensive Cancer Network (NCCN) guideline.

RESULTS: Complications occurred in 5 patients undergoing breast reconstruction of permanent gel after NSM, including 1 case of haemorrhage, 2 cases of infection, and 2 cases of local skin necrosis. Primary healing of incision was obtained in the others. No nipple necrosis was observed in patients undergoing NSM. All the patients were followed up 14-88 months (median, 40 months). At 10 months after operation, the aesthetic results were excellent in 40 cases, good in 33 cases, fair in 14 cases, and poor in 2 cases, with an excellent and good rate of 82%. No recurrence or metastasis was found during follow-up.

CONCLUSION: The SSM or NSM is feasible and oncological safe for patients who are not fit for BCS, with satisfactory aesthetic result.}, } @article {pmid24061465, year = {2013}, author = {Rathore, AS and Kumar, S and Konwar, R and Srivastava, AN and Makker, A and Goel, MM}, title = {Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.}, journal = {Indian journal of cancer}, volume = {50}, number = {3}, pages = {239-244}, doi = {10.4103/0019-509X.118744}, pmid = {24061465}, issn = {1998-4774}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*immunology/*mortality/pathology ; CD3 Complex/immunology ; Carcinoma, Ductal, Breast/*immunology/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, abstract = {BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast.

MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables.

RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021).

CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.}, } @article {pmid24059386, year = {2013}, author = {Seo, M and Chang, JM and Kim, WH and Park, IA and Lee, SH and Cho, N and Moon, WK}, title = {Columnar cell lesions without atypia initially diagnosed on breast needle biopsies: is imaging follow-up enough?.}, journal = {AJR. American journal of roentgenology}, volume = {201}, number = {4}, pages = {928-934}, doi = {10.2214/AJR.12.9906}, pmid = {24059386}, issn = {1546-3141}, mesh = {Adult ; Aged ; Biopsy, Needle/*statistics & numerical data ; Breast Neoplasms/*diagnosis/*epidemiology ; Female ; Humans ; Incidence ; Mammography/*statistics & numerical data ; Middle Aged ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The purpose of this study was to evaluate the underestimation rate and predictive factor of underestimation of columnar cell lesions (CCLs) without atypia diagnosed through breast core needle biopsies (CNBs).

MATERIALS AND METHODS: From January 2007 through December 2011, 141 CCLs without atypia, including columnar cell change and columnar cell hyperplasia, were diagnosed in 138 women by CNB. Excisional (n = 16) or imaging follow-up (n = 125) findings were available in all cases. On a per-lesion basis, the underestimation rate and predictive factor of underestimation were evaluated.

RESULTS: Among the 16 surgically excised lesions, there were two malignancies (one ductal carcinoma in situ and one invasive ductal carcinoma) and one lobular carcinoma in situ. Overall, the pooled underestimation rate of malignancy was 1.4% (2/141). With regard to lesion variables, the mean lesion size was significantly larger in the underestimation group of CCLs (p = 0.007). Fine pleomorphic morphology of microcalcifications (p < 0.001), the distribution of the microcalcifications (p = 0.007), BI-RADS final assessment (p = 0.001), and imaging-pathologic correlation (p < 0.001) were significantly associated with underestimation. Multivariate analysis showed that fine pleomorphic morphology of microcalcifications (p < 0.0001) was an independent predictor of underestimation in 58 lesions with microcalcifications on mammography.

CONCLUSION: The overall underestimation rate of malignancy was 1.4%. Imaging follow-up is reasonable for CCLs without atypia at CNB, especially in small lesions with less suspicious imaging findings. Fine pleomorphic microcalcifications and higher BI-RADS category might be helpful in the prediction of underestimation of a high-risk lesion or malignancy.}, } @article {pmid24058567, year = {2013}, author = {Assi, J and Srivastava, G and Matta, A and Chang, MC and Walfish, PG and Ralhan, R}, title = {Transglutaminase 2 overexpression in tumor stroma identifies invasive ductal carcinomas of breast at high risk of recurrence.}, journal = {PloS one}, volume = {8}, number = {9}, pages = {e74437}, pmid = {24058567}, issn = {1932-6203}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/*pathology ; Carcinoma, Ductal, Breast/*enzymology/*pathology ; Cytoplasm/enzymology/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Focal Adhesion Protein-Tyrosine Kinases ; GTP-Binding Proteins ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/*enzymology/*pathology ; Phosphorylation ; Protein Glutamine gamma Glutamyltransferase 2 ; Risk Factors ; Stromal Cells/enzymology/pathology ; Transglutaminases/*metabolism ; }, abstract = {INTRODUCTION: Molecular markers for predicting breast cancer patients at high risk of recurrence are urgently needed for more effective disease management. The impact of alterations in extracellular matrix components on tumor aggressiveness is under intense investigation. Overexpression of Transglutaminase 2 (TG2), a multifunctional enzyme, in cancer cells impacts epithelial mesenchymal transition, growth, invasion and interactions with tumor microenvironment. The objective of our study is to determine the clinical relevance of stromal TG2 overexpression and explore its potential to identify breast cancers at high risk of recurrence.

METHODS: This retrospective study is based on immunohistochemical analysis of TG2 expression in normal breast tissues (n = 40) and breast cancers (n = 253) with clinical, pathological and follow-up data available for up to 12 years. TG2 expression was correlated with clinical and pathological parameters as well as disease free survival (DFS) of breast cancer patients.

RESULTS: Stromal TG2 overexpression was observed in 114/253 (45.0%) breast cancer tissues as compared to breast normal tissues. Among invasive ductal carcinomas (IDC) of the breast, 97/168 (57.7%) showed strong TG2 expression in tumor stroma. Importantly, IDC patients showing stromal TG2 accumulation had significantly reduced DFS (mean DFS = 110 months) in comparison with patients showing low expression (mean DFS = 130 months) in Kaplan-Meier survival analysis (p<0.001). In Cox multivariate regression analysis, stromal TG2 accumulation was an independent risk factor for recurrence (p = 0.006, Hazard's ratio, H.R. = 3.79). Notably, these breast cancer patients also showed immunostaining of N-epsilon gamma-glutamyl lysine amino residues in tumor stroma demonstrating the transamidating activity of TG2.

CONCLUSIONS: Accumulation of TG2 in tumor stroma is an independent risk factor for identifying breast cancer patients at high risk of recurrence. TG2 overexpression in tumor stroma may serve as a predictor of poor prognosis for IDC of the breast.}, } @article {pmid24054033, year = {2013}, author = {Moon, A and Lim, SJ and Jo, YH and Lee, S and Kim, JY and Lee, J and Park, JH}, title = {Downregulation of GLTSCR2 expression is correlated with breast cancer progression.}, journal = {Pathology, research and practice}, volume = {209}, number = {11}, pages = {700-704}, doi = {10.1016/j.prp.2013.07.010}, pmid = {24054033}, issn = {1618-0631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Time Factors ; Tissue Array Analysis ; Transfection ; Tumor Suppressor Proteins/genetics/*metabolism ; Young Adult ; }, abstract = {Glioma tumor-suppressor candidate region gene2 (GLTSCR2) is a recently identified nucleolus-localized protein participating in the regulation of cell cycle progression and apoptosis. Down-regulation of GLTSCR2 in several types of cancers and increased transforming activity in GLTSCR2-downregulated cancer cells indicated its tumor suppressive potential. The aim of this study was to evaluate GLTSCR2 expression in breast cancer and to investigate the question of whether reduced expression of GLTSCR2 may have any pathological significance in breast cancer development or progression. In this study, we performed quantitative RT-PCR and immunohistochemistry to evaluate the expression of GLTSCR2 and relevance with clinicopathological factors in the invasive ductal carcinoma (IDC). GLTSCR2 expression was reduced in 48% of IDC (n=426) by a semi-quantitative scoring system using tissue microarray. GLTSCR2 mRNA was significantly reduced by 0.16 fold in 15 out of 17 (88%) cases of IDC. Reduction of GLTSCR2 was significantly correlated with increased histological grade (p<0.005), increased tumor size (p<0.001), axillary lymph node involvement (p<0.001) and decreased disease free survival (p<0.025). In addition, we show that upregulation of GLTSCR2 decreases the invasive potential of breast cancer cells. Taken together, our data suggest that GLTCR2 may play a role in the tumorigenesis, progression and biological behavior in breast cancer.}, } @article {pmid24040977, year = {2013}, author = {Večeřová, L and Bendová, M}, title = {[Diagnosis of minimal breast cancers].}, journal = {Ceska gynekologie}, volume = {78}, number = {4}, pages = {322-328}, pmid = {24040977}, issn = {1210-7832}, mesh = {Adult ; Aged ; Biopsy/*methods ; Breast Neoplasms/*diagnosis ; Carcinoma, Lobular/*diagnosis ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Neoplasm Staging/*methods ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {DESIGN: This is a retrospective study evaluating the minimum detection cancers in the group of women mammographically examined in our department. The study covers the period from 1. 1. 2012 to 31. 12. 2012. Interestingly we introduced several interesting case studies.

OBJECTIVE: 1. Confirmation upward trend in the number of minimal breast cancers, stage T1. 2. The need for multidisciplinary cooperation for quick minimal surgical intervention and effective cancer treatment.

SETTING: Department of Radiology, Department of Gynecology and Obstetrics, Third Faculty of Medicine Charles University, Faculty Hospital KV, Prague.

METHODS: The methodology is based on a retrospective evaluation of the number of participants, regardless of age, that come for examination the workplace Breast Radiologists in 2012. Of all the tests are then evaluated the number and types of histological proven cancer, focusing on cancer detection stage T1 and other solutions from surgery after cancer treatment.

RESULTS: In 2012 it was made in 6700 FNKV screening mammography, of this number, 45 were confirmed malignant tumors in asymptomatic women. In 2012 it was simultaneously performed 2276 diagnostic mammography in women with clinically palpable resistance, and malignant tumors was confirmed in 122 women. Overall, mammographically and ultrasonographically examined 10 146 women for the year 2012. Of the 167 women with histologically confirmed malignant tumor. Brest carcinoma, stage T1, was diagnosed in 34% of patients and 66% of patients were malignant bearing greater than 10mm. The most common histological type of breast cancer in our department during the period from 1. 1. 2012 to 31. 12. 2012 was invasive ductal carcinoma (DIC) and in 82% of invasive lobular carcinoma (LIC) was diagnosed in 10%, mixed DIC and LIC in 4% and other cancers represented 4%.

CONCLUSION: The diagnosis mode, core cut biopsy with histological conclusion, preoperative marking bearings in the presence of the surgeon, assessment resection, definitive histology, mammary team, cancer treatment, subsequent postoperative control at one workplace, is in terms of the patient not only effective, individualized and complex, but also cost effective.}, } @article {pmid24029480, year = {2013}, author = {Li, HG and Liu, F and Han, HY and Yang, YF}, title = {[Application value of multiple phase subtraction imaging of dynamic contrast enhanced magnetic resonance imaging in common breast tumor].}, journal = {Zhonghua yi xue za zhi}, volume = {93}, number = {17}, pages = {1318-1320}, pmid = {24029480}, issn = {0376-2491}, mesh = {Adult ; Aged ; *Angiography, Digital Subtraction ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the application value of multiple phase subtraction imaging of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in common breast tumor.

METHODS: All radiographic and MRI data of 72 patients with histological proved common breast tumor were analyzed retrospectively. Prior to an injection of gadolinium-diethylenetriaminepentaacetate (GD-DTPA), 3D mask scans were performed. Then 9 consecutive phases of imaging were acquired. After the drawing of time-signal intensity curve, he first and second phases were selected to perform subtraction with the mask, rebuild 3D maximum intensity projection and analyze the application value of subtracted and 3D maximum intensity projection (MIP) reformation images. Chi-square test was used for the analyses of benign and malignant breast tumors.

RESULTS: There were 83 lesions in 72 patients. Among 18 cases of fibro adenoma, 23 lesions had no tumor vessel. For the detecting ratio of lesions, the first and second phase subtraction imaging had no statistics difference. Only one intraductal papilloma with ductal carcinoma in situ (DCIS) had tumor vessel in 4 intraductal papilloma patients. Among 5 DCIS cases, one of them had small curved tumor vessel. And 51 lesions were found in 45 infiltrating ductal carcinoma (IDC) cases. Tumor vessels could be seen in all IDC cases. And 37 cases had multiple tumor vessels while 8 cases had single tumor vessel. When the first phase was used for subtraction, 36 lesions were found. On the other hand, 51 lesions were found in the second phase subtraction. There were significant differences between them.

CONCLUSION: No significant differences exist in benign breast tumor on differential phase subtraction images of DCE-MRI, but there are significant differences in malignant breast tumor. It is very important to detect the lesions and show the tumor vessels by rebuilding multiple phase subtraction.}, } @article {pmid24028863, year = {2013}, author = {Walcourt, A and Kurantsin-Mills, J and Kwagyan, J and Adenuga, BB and Kalinowski, DS and Lovejoy, DB and Lane, DJ and Richardson, DR}, title = {Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.}, journal = {Journal of inorganic biochemistry}, volume = {129}, number = {}, pages = {43-51}, pmid = {24028863}, issn = {1873-3344}, support = {UH1HL03679/HL/NHLBI NIH HHS/United States ; UL1 RR031975/RR/NCRR NIH HHS/United States ; UL1 TR000101/TR/NCATS NIH HHS/United States ; 5 SO6 GM008016-39/GM/NIGMS NIH HHS/United States ; UL1RR031975/RR/NCRR NIH HHS/United States ; 2MO1RR10284/RR/NCRR NIH HHS/United States ; M01 RR010284/RR/NCRR NIH HHS/United States ; S06 GM008016/GM/NIGMS NIH HHS/United States ; UH1 HL003679/HL/NHLBI NIH HHS/United States ; G12 MD007597/MD/NIMHD NIH HHS/United States ; G12MD007597/MD/NIMHD NIH HHS/United States ; }, mesh = {*Antimalarials/chemistry/pharmacology ; Erythrocyte Membrane/chemistry/*metabolism ; Hemolysis/drug effects ; Humans ; *Hydrazones/chemistry/pharmacology ; *Iron Chelating Agents/chemistry/pharmacology ; Plasmodium falciparum/*metabolism ; *Semicarbazides/chemistry/pharmacology ; }, abstract = {Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.}, } @article {pmid24022309, year = {2013}, author = {El Deeb, NM and Mehanna, RA}, title = {Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression.}, journal = {Turk patoloji dergisi}, volume = {29}, number = {3}, pages = {193-200}, doi = {10.5146/tjpath.2013.01186}, pmid = {24022309}, issn = {1309-5730}, mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/metabolism/pathology ; Carcinoma, Ductal, Breast/*immunology/metabolism/pathology ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Vascular Endothelial Growth Factor A/*biosynthesis ; }, abstract = {OBJECTIVE: Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters.

MATERIAL AND METHOD: Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor.

RESULTS: Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P < 0.001). Immature dendritic cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104).

CONCLUSION: Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.}, } @article {pmid24021901, year = {2013}, author = {Salehi, AH and Omeroglu, G and Kanber, Y and Omeroglu, A}, title = {Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall.}, journal = {International journal of surgical pathology}, volume = {21}, number = {6}, pages = {610-612}, doi = {10.1177/1066896913502228}, pmid = {24021901}, issn = {1940-2465}, mesh = {Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Choristoma ; *Fallopian Tubes ; Female ; Frozen Sections ; Humans ; Lymphatic Diseases/*pathology ; Lymphatic Metastasis/*pathology ; Sentinel Lymph Node Biopsy ; }, abstract = {Intraoperative assessment of sentinel lymph nodes at time of surgical excision of primary breast carcinoma is a crucial step in the determination of cancer extent and the need for further axillary dissection. Benign epithelial inclusions in axillary lymph nodes can mimic metastatic carcinoma and are a well-known pitfall during examination of these nodes in frozen or permanent sections. Most often, these inclusions consists of heterotopic mammary glands and are familiar to the practicing pathologist. Here, however, we present a rare case of endosalpingiosis in the axillary lymph nodes of a breast cancer patient and describe our experience and effort to characterize the lesion. Simulating a metastatic focus of invasive ductal carcinoma, the glandular inclusions lacked myoepithelial cells and failed to stain with myoepithelial markers. However, consistent with a Mullerian origin, the inclusions demonstrated strong staining with PAX-8 and WT-1. Although endosalpingiotic inclusions are not uncommonly encountered in subdiaphragmatic lymph nodes, they are an extremely rare finding above the diaphragm. Pathologists must be aware of these lesions and their ability to imitate metastatic gland-forming carcinoma during frozen section or permanent examination of axillary lymph nodes.}, } @article {pmid24018805, year = {2013}, author = {Zhou, M}, title = {Intraductal carcinoma of the prostate: the whole story.}, journal = {Pathology}, volume = {45}, number = {6}, pages = {533-539}, doi = {10.1097/PAT.0b013e3283653322}, pmid = {24018805}, issn = {1465-3931}, mesh = {Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Prostatic Neoplasms/genetics/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is characterised by proliferation of malignant secretory cells that markedly expand prostatic ducts and acini. Its morphological features and diagnostic criteria have been refined in recent studies. Its molecular characteristics have also been increasingly elucidated. IDC-P is strongly associated with high grade and high volume invasive prostate cancer and unfavourable clinical outcomes. Therefore, it is critical to recognise and report IDC-P, especially in prostate biopsies where the clinical implications of the diagnosis are greatest. IDC-P has to be distinguished from several other prostate lesions with similar histological appearance. The distinction between IDC-P and high grade prostatic intraepithelial neoplasia is most important as they have drastically different implications for patient management. IDC-P is an uncommon finding in prostate biopsies, and is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy. This article will review the historical aspect, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.}, } @article {pmid24009625, year = {2013}, author = {Roberts, JA and Zhou, M and Park, YW and Ro, JY}, title = {Intraductal carcinoma of prostate: a comprehensive and concise review.}, journal = {Korean journal of pathology}, volume = {47}, number = {4}, pages = {307-315}, pmid = {24009625}, issn = {1738-1843}, abstract = {Intraductal carcinoma of the prostate (IDC-P) is defined as a proliferation of prostate adenocarcinoma cells distending and spanning the lumen of pre-existing benign prostatic ducts and acini, with at least focal preservation of basal cells. Studies demonstrate that IDC-P is strongly associated with high-grade (Gleason grades 4/5), large-volume invasive prostate cancers. In addition, recent genetic studies indicate that IDC-P represents intraductal spread of invasive carcinoma, rather than a precursor lesion. Some of the architectural patterns in IDC-P exhibit architectural overlap with one of the main differential diagnoses, high-grade prostatic intraepithelial neoplasia (HGPIN). In these instances, additional diagnostic criteria for IDC-P, including marked nuclear pleomorphism, non-focal comedonecrosis (>1 duct showing comedonecrosis), markedly distended normal ducts/acini, positive nuclear staining for ERG, and cytoplasmic loss of PTEN by immunohistochemistry, can help make the distinction. This distinction between IDC-P and HGPIN is of critical importance because IDC-P has an almost constant association with invasive carcinoma and has negative clinical implications, including shorter relapse-free survival, early biochemical relapse, and metastatic failure rate after radiotherapy. Therefore, IDC-P should be reported in prostate biopsies and radical prostatectomies, regardless of the presence of an invasive component. This article will review the history, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.}, } @article {pmid24004816, year = {2013}, author = {Okubo, M and Tada, K and Niwa, T and Nishioka, K and Tsuji, E and Ogawa, T and Seto, Y}, title = {A case of breast cancer in the axillary tail of Spence - enhanced magnetic resonance imaging and positron emission tomography for diagnostic differentiation and preoperative treatment decision.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {217}, pmid = {24004816}, issn = {1477-7819}, mesh = {Adenocarcinoma/*diagnosis/surgery ; Adult ; Axilla ; Breast Neoplasms/*diagnosis/surgery ; Decision Making ; Diagnosis, Differential ; Female ; Humans ; *Magnetic Resonance Imaging ; *Multimodal Imaging ; *Positron-Emission Tomography ; Preoperative Care ; Prognosis ; }, abstract = {BACKGROUND: The management of cancer in the axillary area depends on the etiology of the tumor.

CASE REPORT: A 37-year-old woman presented with a 2 cm mass in the axillary fossa. Core needle biopsy revealed adenocarcinoma. There were no abnormal breast findings on physical examination, mammography, or ultrasonography. However, enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET) showed a segmentally-distributed, abnormal area in the upper-outer quadrant, continuous with the axillary mass. Samples of this area obtained by vacuum-assisted biopsy showed intraductal carcinoma. These findings indicated that the axillary lesion was a part of primary breast cancer originating from the axillary tail. Based on these results, the patient underwent total mastectomy with sentinel lymph node biopsy. Pathological examination of the specimen showed invasive ductal carcinoma accompanied by intraductal carcinoma extending up to 8.5 cm. Our case suggests that enhanced MRI and PET can provide useful preoperative information for the management of axillary breast lesions.}, } @article {pmid24002514, year = {2013}, author = {Shai, A and Hirschberger, G}, title = {On death and fear: a personal reflection on the value of social psychology research to the practice of oncologists.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {28}, pages = {3605-3606}, doi = {10.1200/JCO.2013.51.4299}, pmid = {24002514}, issn = {1527-7755}, mesh = {*Adaptation, Psychological ; Adult ; *Behavioral Research ; Breast Neoplasms/psychology/therapy ; *Death ; Fear/*psychology ; Female ; Humans ; *Medical Oncology ; *Physician-Patient Relations ; Physicians/*psychology ; *Psychology, Social ; Terminally Ill ; }, } @article {pmid24001613, year = {2013}, author = {Zhang, B and Yin, C and Li, H and Shi, L and Liu, N and Sun, Y and Lu, S and Liu, Y and Sun, L and Li, X and Chen, W and Qi, Y}, title = {Nir1 promotes invasion of breast cancer cells by binding to chemokine (C-C motif) ligand 18 through the PI3K/Akt/GSK3β/Snail signalling pathway.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {49}, number = {18}, pages = {3900-3913}, doi = {10.1016/j.ejca.2013.07.146}, pmid = {24001613}, issn = {1879-0852}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Calcium-Binding Proteins/genetics/*metabolism ; Cell Line, Tumor ; Chemokines, CC/genetics/*metabolism ; Chromones/pharmacology ; Epithelial-Mesenchymal Transition/drug effects/genetics ; Female ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; MCF-7 Cells ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Morpholines/pharmacology ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Protein Binding ; Proto-Oncogene Proteins c-akt/metabolism ; *Signal Transduction ; Snail Family Transcription Factors ; Transcription Factors/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Chemokine (C-C motif) ligand 18 (CCL18), which is derived from tumour-associated macrophages (TAMs), plays a critical role in promoting breast cancer metastasis via its receptor, PYK2 N-terminal domain interacting receptor 1 (Nir1). However, the molecular mechanism by which Nir1 promotes breast cancer metastasis by binding to CCL18 remains elusive. In this study, Nir1 expression was associated with lymph node and distant metastasis in patients with invasive ductal carcinoma. For the first time, we report that Nir1 binding to CCL18 promotes the phosphorylation of Akt, LIN-11, Isl1 and MEC-3 protein domain kinase (LIMK), and cofilin, which is a critical step in cofilin recycling and actin polymerisation. Interestingly, Nir1 binding to CCL18 can enhance cell mesenchymal properties and induce epithelial-mesenchymal transition (EMT). Mechanistically, Nir1 binding to CCL18 stabilises Snail via the Akt/GSK3β signalling pathway. In support of these observations, Nir1 binding to CCL18 promoted lung metastasis and LY294002 could inhibit it in vivo. In summary, our in vitro and in vivo results indicate that Nir1 binding to CCL18 plays an important role in breast cancer invasion/metastasis. This study identified both Nir1 and CCL18 as potential anti-invasion targets for therapeutic intervention in breast cancer.}, } @article {pmid23996076, year = {2013}, author = {Kariagina, A and Xie, J and Langohr, IM and Opreanu, RC and Basson, MD and Haslam, SZ}, title = {Progesterone decreases levels of the adhesion protein E-cadherin and promotes invasiveness of steroid receptor positive breast cancers.}, journal = {Hormones & cancer}, volume = {4}, number = {6}, pages = {371-380}, pmid = {23996076}, issn = {1868-8500}, support = {U01 ES012800/ES/NIEHS NIH HHS/United States ; U01 ES/CA 012800/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal/*metabolism/pathology ; Cell Line, Tumor ; Estrogens/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Neoplasms, Experimental/*metabolism/pathology ; Neoplasm Invasiveness ; Progesterone/*metabolism ; Promegestone/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Progesterone/metabolism ; Wnt Signaling Pathway ; }, abstract = {Progestins are reported to increase the risk of invasive breast cancers in postmenopausal women receiving hormone therapy with estrogen plus progestin. We report here that estrogen and progesterone receptor positive (ER+PR+) rat mammary tumors arising in the presence of estrogen and progesterone exhibit increased invasiveness and decreased expression of E-cadherin protein compared with tumors growing in the presence of estrogen alone. A similar decrease of E-cadherin expression was observed in human ER+PR+ invasive ductal carcinoma compared with ductal carcinoma in situ. In agreement with findings in the rat, estrogen plus progestin R5020 treatment decreased E-cadherin expression in vitro in T47D human breast cancer cells. Decrease of E-cadherin protein was mediated by progesterone receptor B (PRB) and dependent on the activation of the Wnt pathway. These results suggest that progesterone signaling via PRB contributes to tumor invasiveness and can provide an important therapeutic target for treatment of invasive ER+PR+ breast cancers.}, } @article {pmid23988541, year = {2013}, author = {Serra, R and Buffone, G and Perri, P and Renne, M and Amato, B and de Franciscis, S}, title = {Male breast cancer manifesting as cephalic vein thrombosis.}, journal = {Annals of vascular surgery}, volume = {27}, number = {8}, pages = {1188.e9-11}, doi = {10.1016/j.avsg.2013.01.016}, pmid = {23988541}, issn = {1615-5947}, mesh = {Aged ; Anticoagulants/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms, Male/*complications/diagnosis/therapy ; Carcinoma, Ductal, Breast/*complications/diagnosis/therapy ; Chemotherapy, Adjuvant ; Humans ; Male ; Mastectomy, Simple ; Treatment Outcome ; Ultrasonography, Doppler, Duplex ; Upper Extremity/*blood supply ; Venous Thromboembolism/diagnosis/drug therapy/*etiology ; Venous Thrombosis/diagnosis/drug therapy/*etiology ; }, abstract = {Male breast cancer is an uncommon disease with a low annual prevalence in Western countries. Venous thromboembolism may be associated during malignancy of the breast. We report a 70-year-old man who presented with superficial vein thrombosis of right upper limb that predicted the diagnosis of breast invasive ductal carcinoma. Key issues surrounding the diagnosis, treatment, and relationship between breast cancer and venous disorders are discussed. Breast cancer and venous thromboembolism are 2 conditions that are often correlated more than expected, and attention to the combination of these clinical presentations is required.}, } @article {pmid23983079, year = {2014}, author = {Nakash, O and Levav, I and Aguilar-Gaxiola, S and Alonso, J and Andrade, LH and Angermeyer, MC and Bruffaerts, R and Caldas-de-Almeida, JM and Florescu, S and de Girolamo, G and Gureje, O and He, Y and Hu, C and de Jonge, P and Karam, EG and Kovess-Masfety, V and Medina-Mora, ME and Moskalewicz, J and Murphy, S and Nakamura, Y and Piazza, M and Posada-Villa, J and Stein, DJ and Taib, NI and Zarkov, Z and Kessler, RC and Scott, KM}, title = {Comorbidity of common mental disorders with cancer and their treatment gap: findings from the World Mental Health Surveys.}, journal = {Psycho-oncology}, volume = {23}, number = {1}, pages = {40-51}, pmid = {23983079}, issn = {1099-1611}, support = {R01 DA016558/DA/NIDA NIH HHS/United States ; R03 TW006481/TW/FIC NIH HHS/United States ; R01 MH069864/MH/NIMH NIH HHS/United States ; R01-MH069864/MH/NIMH NIH HHS/United States ; U01 MH060220/MH/NIMH NIH HHS/United States ; R13-MH066849/MH/NIMH NIH HHS/United States ; R01 MH070884/MH/NIMH NIH HHS/United States ; R01 MH059575/MH/NIMH NIH HHS/United States ; K05 DA015799/DA/NIDA NIH HHS/United States ; R03-TW006481/TW/FIC NIH HHS/United States ; R03 TW006481-01/TW/FIC NIH HHS/United States ; R13 MH066849/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Comorbidity ; Developed Countries/statistics & numerical data ; Developing Countries/statistics & numerical data ; Female ; Global Health/statistics & numerical data ; Health Surveys ; Humans ; Male ; Mental Disorders/complications/*epidemiology/therapy ; Mental Health Services/statistics & numerical data ; Neoplasms/complications/epidemiology/*psychology ; Socioeconomic Factors ; Survivors/psychology/statistics & numerical data ; }, abstract = {OBJECTIVE: This study aimed to study the comorbidity of common mental disorders (CMDs) and cancer, and the mental health treatment gap among community residents with active cancer, cancer survivors and cancer-free respondents in 13 high-income and 11 low-middle-income countries.

METHODS: Data were derived from the World Mental Health Surveys (N = 66,387; n = 357 active cancer, n = 1373 cancer survivors, n = 64,657 cancer-free respondents). The World Health Organization/Composite International Diagnostic Interview was used in all surveys to estimate CMDs prevalence rates. Respondents were also asked about mental health service utilization in the preceding 12 months. Cancer status was ascertained by self-report of physician's diagnosis.

RESULTS: Twelve-month prevalence rates of CMDs were higher among active cancer (18.4%, SE = 2.1) than cancer-free respondents (13.3%, SE = 0.2) adjusted for sociodemographic confounders and other lifetime chronic conditions (adjusted odds ratio (AOR) = 1.44, 95% CI 1.05-1.97). CMD rates among cancer survivors (14.6%, SE = 0.9) compared with cancer-free respondents did not differ significantly (AOR = 0.95, 95% CI 0.82-1.11). Similar patterns characterized high-income and low-middle-income countries. Of respondents with active cancer who had CMD in the preceding 12 months, 59% sought services for mental health problems (SE = 5.3). The pattern of service utilization among people with CMDs by cancer status (highest among persons with active cancer, lower among survivors and lowest among cancer-free respondents) was similar in high-income (64.0%, SE = 6.0; 41.2%, SE = 3.0; 35.6%, SE = 0.6) and low-middle-income countries (46.4%, SE = 11.0; 22.5%, SE = 9.1; 17.4%, SE = 0.7).

CONCLUSIONS: Community respondents with active cancer have higher CMD rates and high treatment gap. Comprehensive cancer care should consider both factors.}, } @article {pmid23982804, year = {2014}, author = {Jennings, VA and Ilett, EJ and Scott, KJ and West, EJ and Vile, R and Pandha, H and Harrington, K and Young, A and Hall, GD and Coffey, M and Selby, P and Errington-Mais, F and Melcher, AA}, title = {Lymphokine-activated killer and dendritic cell carriage enhances oncolytic reovirus therapy for ovarian cancer by overcoming antibody neutralization in ascites.}, journal = {International journal of cancer}, volume = {134}, number = {5}, pages = {1091-1101}, pmid = {23982804}, issn = {1097-0215}, support = {13244/CRUK_/Cancer Research UK/United Kingdom ; R01 CA107082/CA/NCI NIH HHS/United States ; R01 CA175386/CA/NCI NIH HHS/United States ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antibodies, Neutralizing/*immunology ; Apoptosis ; Ascites/*immunology ; Cytokines/biosynthesis ; Dendritic Cells/*immunology ; Female ; Humans ; Killer Cells, Lymphokine-Activated/*immunology ; *Oncolytic Virotherapy ; Ovarian Neoplasms/immunology/*therapy ; Reoviridae/*immunology ; Tumor Cells, Cultured ; }, abstract = {Reovirus is an oncolytic virus (OV), which acts by both direct tumor cell killing and priming of antitumor immunity. A major obstacle for effective oncolytic virotherapy is effective delivery of OV to tumor cells. Ovarian cancer is often confined to the peritoneal cavity and therefore i.p. delivery of reovirus may provide the ideal locoregional delivery, avoiding systemic dissemination. However, ovarian cancer is associated with an accumulation of ascitic fluid, which may interfere with oncolytic viral therapy. Here, we investigated the effect of ascites on reovirus-induced oncolysis against primary ovarian cancer cells and ovarian cancer cell lines. In the absence of ascites, reovirus was cytotoxic against ovarian cancer cells; however, cytotoxicity was abrogated in the presence of ascitic fluid. Neutralizing antibodies (NAb) were identified as the cause of this inhibition. Loading OV onto cell carriers may facilitate virus delivery in the presence of NAb and immune cells which have their own antitumor effector activity are particularly appealing. Immature dendritic cells (iDC), Lymphokine-activated killer (LAK) cells and LAKDC cocultures were tested as potential carriers for reovirus for tumor cell killing and immune cell priming. Reovirus-loaded LAKDC, and to a lesser degree iDC, were able to: (i) protect from NAb and hand-off reovirus for tumor cell killing; (ii) induce a proinflammatory cytokine milieu (IFNɣ, IL-12, IFNα and TNFα) and (iii) generate an innate and specific antitumor adaptive immune response. Hence, LAKDC pulsed with reovirus represent a novel, clinically practical treatment for ovarian cancer to maximise both direct and innate/adaptive immune-mediated tumor cell killing.}, } @article {pmid23972507, year = {2015}, author = {Ogawa, T}, title = {Goldilocks mastectomy for obese Japanese females with breast ptosis.}, journal = {Asian journal of surgery}, volume = {38}, number = {4}, pages = {232-235}, doi = {10.1016/j.asjsur.2013.07.003}, pmid = {23972507}, issn = {0219-3108}, mesh = {Aged ; Breast Neoplasms/complications/*surgery ; Carcinoma, Ductal, Breast/complications/*surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/*surgery ; Female ; Humans ; Japan ; Mastectomy, Subcutaneous/*methods ; Obesity/*complications ; }, abstract = {The Goldilocks mastectomy is a method that uses redundant mastectomy flap tissue alone to create a breast mound in female American patients with macromastia. Goldilocks mastectomy was performed for obese Japanese females with breast ptosis, and its indications were considered for Japanese female patients. This report presents the results of five patients who underwent Goldilocks mastectomy, including one with bilateral breast cancer. The average age of the patients was 72 years (range: 67-76 years). The body mass index (BMI) was more than 25 in all the cases. Four patients had invasive ductal carcinoma, and one patient had noninvasive ductal carcinoma of bilateral breasts. The cosmetic results were found to be good in two cases [a patient with bilateral breast cancer and a severely obese patient (BMI = 39)]. The cosmetic results in the other three cases were poor. Although the reconstructed breast size was small, this procedure resulted in better cosmetic results than what would be achieved with the usual method of mastectomy for Japanese patients with bilateral breast cancer and severely obese Japanese patients.}, } @article {pmid23971832, year = {2013}, author = {Borges, S and Döppler, H and Perez, EA and Andorfer, CA and Sun, Z and Anastasiadis, PZ and Thompson, E and Geiger, XJ and Storz, P}, title = {Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis.}, journal = {Breast cancer research : BCR}, volume = {15}, number = {2}, pages = {R66}, pmid = {23971832}, issn = {1465-542X}, support = {CA116201-03DR4/CA/NCI NIH HHS/United States ; GM086435/GM/NIGMS NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; R21 NS070117/NS/NINDS NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antimetabolites, Antineoplastic/pharmacology ; Apoptosis ; Azacitidine/*analogs & derivatives/pharmacology ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Carcinoma, Ductal, Breast/drug therapy/genetics/secondary ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/genetics/secondary ; Carcinoma, Lobular/drug therapy/genetics/secondary ; Cell Movement ; Cell Proliferation ; DNA Methylation/drug effects ; Decitabine ; Epigenesis, Genetic/*drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing ; Humans ; Immunoenzyme Techniques ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness ; Promoter Regions, Genetic/*genetics ; Protein Kinase C/*antagonists & inhibitors/genetics ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: DNA methylation-induced silencing of genes encoding tumor suppressors is common in many types of cancer, but little is known about how such epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes protein kinase D1 (PKD1), a serine/threonine kinase that is expressed in cells of the normal mammary gland, where it maintains the epithelial phenotype by preventing epithelial-to-mesenchymal transition.

METHODS: The status of PRKD1 promoter methylation was analyzed by reduced representation bisulfite deep sequencing, methylation-specific PCR (MSP-PCR) and in situ MSP-PCR in invasive and noninvasive breast cancer lines, as well as in humans in 34 cases of "normal" tissue, 22 cases of ductal carcinoma in situ, 22 cases of estrogen receptor positive, HER2-negative (ER+/HER2-) invasive lobular carcinoma, 43 cases of ER+/HER2- invasive ductal carcinoma (IDC), 93 cases of HER2+ IDC and 96 cases of triple-negative IDC. A reexpression strategy using the DNA methyltransferase inhibitor decitabine was used in vitro in MDA-MB-231 cells as well as in vivo in a tumor xenograft model and measured by RT-PCR, immunoblotting and immunohistochemistry. The effect of PKD1 reexpression on cell invasion was analyzed in vitro by transwell invasion assay. Tumor growth and metastasis were monitored in vivo using the IVIS Spectrum Pre-clinical In Vivo Imaging System.

RESULTS: Herein we show that the gene promoter of PRKD1 is aberrantly methylated and silenced in its expression in invasive breast cancer cells and during breast tumor progression, increasing with the aggressiveness of tumors. Using an animal model, we show that reversion of PRKD1 promoter methylation with the DNA methyltransferase inhibitor decitabine restores PKD1 expression and blocks tumor spread and metastasis to the lung in a PKD1-dependent fashion.

CONCLUSIONS: Our data suggest that the status of epigenetic regulation of the PRKD1 promoter can provide valid information on the invasiveness of breast tumors and therefore could serve as an early diagnostic marker. Moreover, targeted upregulation of PKD1 expression may be used as a therapeutic approach to reverse the invasive phenotype of breast cancer cells.}, } @article {pmid23970633, year = {2014}, author = {Nakiwogga-Muwanga, A and Katabira, E and Kiragga, A and Kambugu, A and Nakibuuka-Lubwama, E and Manabe, YC and Alamo, ST and Colebunders, R}, title = {Factors before enrolment are associated with being removed from a Pharmacy-only Refill Programme at a large urban HIV/AIDS clinic, Uganda.}, journal = {International journal of STD & AIDS}, volume = {25}, number = {2}, pages = {105-112}, doi = {10.1177/0956462413492715}, pmid = {23970633}, issn = {1758-1052}, mesh = {Adult ; Ambulatory Care Facilities ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Appointments and Schedules ; CD4 Lymphocyte Count ; Case-Control Studies ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/virology ; Health Resources/organization & administration ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Patient Care Team/*organization & administration ; Patient Compliance/*statistics & numerical data ; Pharmacy ; Referral and Consultation/*organization & administration ; Risk Factors ; Uganda ; Urban Population ; Viral Load ; }, abstract = {A Pharmacy-only Refill Programme (PRP) a type of task shifting in which stable HIV-positive patients are managed through pharmacy-only visits instead of physician visits. We performed a study to identify factors for being removed from the PRP in order to establish better referral criteria. The study was performed at the Infectious Disease Clinic (IDC) in Kampala, Uganda. We selected a random sample of 588 patients from 2431 patients on antiretroviral therapy referred to the PRP at least 12 months before commencement of the PRP evaluation. We compared the characteristics of patients who during 12 months of follow-up were removed from the PRP with those who continued to be followed up. Data were abstracted from the IDC data base, the pharmacy register and the patient clinical notes. Of 588 patients, 106 (18%) were removed from the PRP. In multivariate analysis, less than 100% self-reported adherence to antiretroviral therapy, missing at least one scheduled appointment in the six months before referral to the PRP and being on a lopinavir/ritonavir-containing regimen were independently associated with being removed from the PRP. Criteria for referring patients to a PRP should focus on antiretroviral therapy adherence and appointment keeping. Patients on a lopinavir/ritonavir-containing regimen should not be targeted for a PRP. On the other hand a PRP is an efficient strategy that targets stable adherent patients in clinics with high patient load.}, } @article {pmid23967550, year = {2013}, author = {Skotnicki, P and Blecharz, P and Jakubowicz, J and Reinfuss, M and Strzepek, Ł}, title = {Clinical picture of infiltrating lobular carcinoma of the breast: an analysis of 96 patients.}, journal = {European journal of gynaecological oncology}, volume = {34}, number = {3}, pages = {222-226}, pmid = {23967550}, issn = {0392-2936}, mesh = {Age Factors ; Aged ; Axilla ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Female ; Humans ; Incidence ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Metastasis ; }, abstract = {OBJECTIVE: The aim of this study was to present the clinical picture of infiltrating lobular carcinoma (ILC) of the breast.

MATERIALS AND METHODS: A detailed analysis was performed for the group of 96 ILC patients subject to initial surgical treatment in the Krakow Branch of Centre of Oncology between 1983 and 1996. The investigated group was selected out of 2,347 breast cancer patients treated during that period, based on re-examination of histologic specimens of the initial patient group.

RESULTS: The following distinctive demographic and clinical features of ILC were found: average age of patients: 59 years (37 - 83); average duration of pathological symptoms: five months; most frequent site of primary tumor: upper outer quadrant (54.2%); primary tumor Stage: I/II0 (64.6%), III0A (35.4%); tumor size in breast: up to five cm (69.8%), larger than five cm (30.2%); no axillary lymph nodes involvement in 51% of patients; multifocality of lesions in 10% of patients; contralateral disease occurrence in eight percent of patients; atypical pattern of distant metastases, e.g. gastrointestinal system, gynaecologic organs, and cerebral meninges.

CONCLUSIONS: Based on this analysis as well as on literature reports, it was found that the fundamental differences between ILC and infiltrating ductal carcinoma (IDC) included demographic and clinical features as patient age, primary tumor size at diagnosis, incidence of multifocality and contralateral disease, sites of distant metastases, and histopathological status of axillary lymph nodes.}, } @article {pmid23944930, year = {2013}, author = {Osako, T and Takeuchi, K and Horii, R and Iwase, T and Akiyama, F}, title = {Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.}, journal = {Histopathology}, volume = {63}, number = {4}, pages = {509-519}, doi = {10.1111/his.12172}, pmid = {23944930}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/genetics ; Carcinoma/*diagnosis ; Carcinoma, Acinar Cell/diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; *Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Young Adult ; }, abstract = {AIMS: Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers.

METHODS AND RESULTS: We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC.

CONCLUSIONS: In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis.}, } @article {pmid23942617, year = {2013}, author = {McCart Reed, AE and Song, S and Kutasovic, JR and Reid, LE and Valle, JM and Vargas, AC and Smart, CE and Simpson, PT}, title = {Thrombospondin-4 expression is activated during the stromal response to invasive breast cancer.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {463}, number = {4}, pages = {535-545}, pmid = {23942617}, issn = {1432-2307}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/pathology ; Female ; Fibroblasts/metabolism ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stromal Cells/*metabolism ; Thrombospondins/analysis/*biosynthesis ; Transcriptome ; *Tumor Microenvironment ; }, abstract = {The thromobospondins are a family of extracellular glycoproteins that are activated during tissue remodeling processes such as embryogenesis, wound healing and cancer. Thrombospondin-4 (THBS4) is known to have roles in cellular migration, adhesion and attachment, as well as proliferation in different contexts. Data to support a role in cancer biology is increasing, including for gastrointestinal and prostate tumours. Here, using a combination of immunohistochemistry, immunofluorescence and analysis of publicly available genomic and expression data, we present the first study describing the pattern of expression of THBS4 in normal breast and breast cancer. THBS4 was located to the basement membrane of large ducts and vessels in normal breast tissue, but was absent from epithelium and extracellular matrix. There was a significant induction in expression in cancer-associated stroma relative to normal stroma (P = 0.0033), neoplastic epithelium (P < 0.0001) and normal epithelium (P < 0.0001). There was no difference in stromal expression of THBS4 between invasive ductal carcinomas (IDC) and invasive lobular carcinomas (ILC). The THBS4 mRNA levels were variable yet were generally highest in tumours typically rich in stromal content (ILC, ER positive low grade IDC; luminal A and normal-like subtypes). Genomic alterations of the THBS4 gene (somatic mutations and gene copy number) are rare suggesting this dramatic activation in expression is most likely dynamically regulated through the interaction between invading tumour cells and stromal fibroblasts in the local microenvironment. In summary, THBS4 expression in breast cancer-associated extracellular matrix contributes to the activated stromal response exhibited during tumour progression and this may facilitate invasion of tumour cells.}, } @article {pmid23940990, year = {2013}, author = {Milanović, R and Roje, Z and Korusić, A and Deno, IT and Barić, A and Stanec, Z}, title = {Clinical and patohistological factors affecting the 5 year survival rate in a population of Croatian women with invasive ductal breast carcinoma.}, journal = {Collegium antropologicum}, volume = {37}, number = {2}, pages = {459-464}, pmid = {23940990}, issn = {0350-6134}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology ; Carcinoma, Ductal, Breast/*mortality/*secondary ; Croatia/epidemiology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Grading/mortality ; Neoplasm Recurrence, Local/mortality ; Risk Factors ; Survival Rate ; }, abstract = {Breast carcinoma falls into a heterogeneous group of diseases which can be determined by various prognostic factors. The identification of clinical and histopathologic factors is of great value in predicting the progression of tumor growth and survival outcome. Due to a high degree of cell proliferation in breast tumors and high genetic instability of these tumors, as a consequence of defective DNA repair mechanisms, chemotherapy as a treatment option often renders very successful results. During our scientific study of the expression of genes responsible for mismatch repair of DNA in cells of invasive ductal carcinoma we also compared the patient survival rate with the major prognostic factors. This study included 108 patients who were surgically treated for invasive breast cancer at the Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital "Dubrava". The overall survival rate was compared to factors such as initial tumor stage, regional lymph node involvement and distant metastasis. The overall five year survival rate of our patients was 78.7%. Patients without the presence of distant metastasis, a lower rate of local lymph node involvement and a lower. tumor stage statistically had a longer overall survival period. It is important that physicians recognize the various clinico-pathohistological factors in patients with breast carcinoma. This study confirms that this prognostic factors determine the type of treatment required and most important, the patient overall survival period.}, } @article {pmid23938241, year = {2013}, author = {Tolmacz, R}, title = {Forms of concern: toward an intersubjective perspective.}, journal = {American journal of psychoanalysis}, volume = {73}, number = {3}, pages = {271-287}, doi = {10.1057/ajp.2013.14}, pmid = {23938241}, issn = {1573-6741}, mesh = {Countertransference ; *Emotions ; Guilt ; Humans ; *Professional-Patient Relations ; *Psychoanalytic Theory ; *Psychoanalytic Therapy ; }, abstract = {The growing interest in the issue of concern, which appeared relatively late in psychoanalytical literature, resulted in several distinctions. Winnicott distinguished between concern as an expression of guilt and concern as a manifestation of joy, Brenman Pick distinguished between real concern and spurious concern, and Bowlby distinguished between sensitive and compulsive caregiving. The basic concepts of Buber's dialogical philosophy and intersubjective approaches in psychoanalysis have created fertile ground for the study of concern, and enabled us to conceptualize these distinctions in a way that has heretofore been lacking in psychoanalytical thought.}, } @article {pmid23935333, year = {2012}, author = {Gavriilidis, P and Ananiadis, A and Theodoulidis, V and Toskas, I and Barbanis, S}, title = {Ovarian metastasis from breast invasive ductal carcinoma.}, journal = {Hippokratia}, volume = {16}, number = {4}, pages = {391}, pmid = {23935333}, issn = {1108-4189}, } @article {pmid23932764, year = {2014}, author = {Larribe, M and Thomassin-Piana, J and Jalaguier-Coudray, A}, title = {Breast cancers with round lumps: correlations between imaging and anatomopathology.}, journal = {Diagnostic and interventional imaging}, volume = {95}, number = {1}, pages = {37-46}, doi = {10.1016/j.diii.2013.04.003}, pmid = {23932764}, issn = {2211-5684}, mesh = {Adenocarcinoma, Mucinous/diagnosis/pathology ; Breast/*pathology ; Breast Neoplasms/*diagnosis/*pathology/secondary ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Carcinoma, Medullary/diagnosis/pathology ; Carcinoma, Papillary/diagnosis/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Lymphoma/diagnosis/pathology ; *Mammography ; Neoplasm Grading ; Neoplasm Staging ; Phyllodes Tumor/diagnosis/pathology ; Prognosis ; Statistics as Topic ; *Ultrasonography, Mammary ; }, abstract = {A round lump with a well-defined outline is, in most cases, benign. However, in 10 to 20% of all cases, a round and well-defined lump may correspond to a cancer. Most often, it consists of grade III infiltrating ductal carcinoma (IDC). Other histological sub-types may provide round masses with smooth contours: colloid carcinoma (still called mucinous carcinoma), medullary carcinoma, intramammary metastases, intra-cystic papillary carcinoma, lymphoma and high-grade phyllode tumours.}, } @article {pmid23932569, year = {2013}, author = {Pfeiffer, IA and Zinser, E and Strasser, E and Stein, MF and Dörrie, J and Schaft, N and Steinkasserer, A and Knippertz, I}, title = {Leukoreduction system chambers are an efficient, valid, and economic source of functional monocyte-derived dendritic cells and lymphocytes.}, journal = {Immunobiology}, volume = {218}, number = {11}, pages = {1392-1401}, doi = {10.1016/j.imbio.2013.07.005}, pmid = {23932569}, issn = {1878-3279}, mesh = {CD4-Positive T-Lymphocytes/*cytology ; CD8-Positive T-Lymphocytes/*cytology ; Cell Culture Techniques ; Cell Proliferation ; Cells, Cultured ; Cryopreservation ; Dendritic Cells/*cytology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Interleukin-4/metabolism ; Leukocytes, Mononuclear/*cytology ; Plateletpheresis/*methods ; }, abstract = {The demand for human monocyte-derived dendritic cells (moDCs), as well as for primary human B and T lymphocytes for immunological research purposes has been increased in recent years. Classically, these monocytes are isolated from blood, leukapheresis products or buffy coats of healthy donors by plastic adherence of peripheral blood mononuclear cells (PBMCs), followed by stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, while lymphocytes are usually isolated from the non-adherent fraction (NAF) by magnetic cell sorting. However, donor-blood is a limited resource and not every blood bank offers leukapheresis products or buffy coats for laboratory use. Additionally, a leukapheresis is very expensive and also the generation/isolation of cells is time- and cost-intensive. To overcome some of these obstacles, we evaluated if low-cost leukoreduction system chambers (LRSCs), which arise after routine donor plateletpheresis procedures, and are usually discarded, would be an alternative and appropriate source of PBMCs to generate moDCs and to isolate lymphocytes. By analyzing the number and phenotype of immature and mature dendritic cells (DCs), as well as of B and T lymphocytes derived from LRSCs, we found all cells to be of high quantity and quality. Further investigations on DCs comprising transwell migration assays, allogeneic mixed lymphocyte reactions (MLR), cytokine secretion assays, and cytotoxic T cell induction assays revealed high migratory, as well as stimulatory capacity of these cells. In addition, DCs and T cells were efficiently electroporated with mRNA and showed characteristic cytokine production after co-culture, demonstrating LRSCs as an efficient, valid, and economic source for generation of moDCs and lymphocytes for research purposes.}, } @article {pmid23932428, year = {2014}, author = {Seifert, L and Komar, J and Crettenand, F and Dadashi, F and Aminian, K and Millet, GP}, title = {Inter-limb coordination and energy cost in swimming.}, journal = {Journal of science and medicine in sport}, volume = {17}, number = {4}, pages = {439-444}, doi = {10.1016/j.jsams.2013.07.003}, pmid = {23932428}, issn = {1878-1861}, mesh = {Adolescent ; Arm/physiology ; Biomechanical Phenomena/physiology ; Energy Metabolism/*physiology ; Humans ; Leg/physiology ; Motor Skills/*physiology ; Swimming/*physiology ; Young Adult ; }, abstract = {OBJECTIVES: This study investigated the relationship between inter-arm coordination and the energy cost of locomotion in front crawl and breaststroke and explored swimmers' flexibility in adapting their motor organization away from their preferred movement pattern.

DESIGN: Nine front-crawlers performed three 300-m in front crawl and 8 breaststrokers performed three 200-m in breaststroke at constant submaximal intensity and with 5-min rests. Each trial was performed randomly in a different coordination pattern: freely chosen, 'maximal glide' and 'minimal glide'. Two underwater cameras videotaped frontal and side views to analyze speed, stroke rate, stroke length and inter-limb coordination.

METHODS: In front crawl, inter-arm coordination was quantified by the index of coordination (IdC) and the leg beat kicks were counted. In breaststroke, four time gaps quantified the arm to leg coordination (i.e., time between leg and arm propulsions; time between beginning, 90° flexion and end of arm and leg recoveries). The energy cost of locomotion was calculated from gas exchanges and blood lactate concentration.

RESULTS: In both front crawl and breaststroke, the freely chosen coordination corresponded to glide pattern and showed the lowest energy cost (12.8 and 17.1Jkg(-1)m(-1), respectively). Both front-crawlers and breaststrokers were able to reach 'maximal glide' condition (respectively, +35% and +28%) but not 'minimal glide' condition for front crawl.

CONCLUSIONS: The freely chosen pattern appeared more economic because more trained. When coordination was constrained, the swimmers had higher coordination flexibility in breaststroke than in front crawl, suggesting that breaststroke coordination was easier to regulate by changing glide time.}, } @article {pmid23931616, year = {2013}, author = {Watts, K and Li, J and Magi-Galluzzi, C and Zhou, M}, title = {Incidence and clinicopathological characteristics of intraductal carcinoma detected in prostate biopsies: a prospective cohort study.}, journal = {Histopathology}, volume = {63}, number = {4}, pages = {574-579}, doi = {10.1111/his.12198}, pmid = {23931616}, issn = {1365-2559}, mesh = {Aged ; Biopsy ; Carcinoma, Ductal/*epidemiology/*pathology ; Cohort Studies ; Humans ; Incidence ; Male ; Middle Aged ; Prostatic Neoplasms/*epidemiology/*pathology ; }, abstract = {AIMS: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice.

METHODS AND RESULTS: In 1176 prospectively collected PBx, 33 IDC-P cases were identified (2.8%). The mean age of patients with IDC-P was 65 (range 46-79) years and mean serum prostate-specific antigen was 16.2 (range 0.4-105.6) ng/ml. Three (0.26%) IDC-P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1-14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016).

CONCLUSIONS: This is the first prospective study that has investigated the incidence and prognostic significance of IDC-P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC-P in PBx.}, } @article {pmid23928534, year = {2013}, author = {Yang, M and Xu, SP and Ao, QL}, title = {[Expression of fatty acid synthase and its association with HER2 in invasive ductal carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {42}, number = {4}, pages = {257-261}, doi = {10.3760/cma.j.issn.0529-5807.2013.04.010}, pmid = {23928534}, issn = {0529-5807}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Fatty Acid Synthases/*metabolism ; Female ; Fibrocystic Breast Disease/metabolism ; Gene Amplification ; Genes, erbB-2 ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*metabolism ; }, abstract = {OBJECTIVE: To investigate the expression of fatty acid synthase (FAS) in adenosis, atypical ductal epithelial hyperplasia, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of breast, and the correlation of FAS expression with HER2 gene amplification in IDC.

METHODS: Immunohistochemical EnVision method staining for FAS was performed in 100 cases of breast lesions and 10 normal breast tissues. HER2 gene amplification was detected with FISH in 60 cases of IDC.

RESULTS: The cohort included 10 cases of adenosis, 10 atypical ductal epithelial hyperplasia, 20 DCIS (8 high-grade, 9 intermediated-grade and 3 low-grade), and 60 cases of IDC (5 grade 1, 40 grade 2 and 15 grade 3). FAS expression was negative in all 10 normal breast tissues; in the 10 cases of adenosis, strongly positive FAS expression was detected in one case, positive in 2, weakly positive in 4, and negative in 3; in the 10 cases of atypical ductal epithelial hyperplasia, FAS immunohistochemistry showed that 1 was strongly positive, 4 positive, 4 weakly positive, and 1 negative; in the 20 cases of DCIS, FAS immunostaining showed that 12 were strongly positive, 5 positive, 1 weakly positive, and 2 negative; FAS expression showed a clear increasing trend from normal breast tissue, atypical ductal epithelial hyperplasia to DCIS (χ(2) = 42.02, P < 0.01). Likewise, the increasing trend was also demonstrated from adenosis to DCIS (χ(2) = 34.69, P < 0.01). There was also a positive correlation between FAS expression and extent of lesion among normal breast tissue, adenosis, atypical ductal epithelial hyperplasia and DCIS (χ(2) = 86.02, P < 0.01; r = 0.568, P < 0.01). FAS expression was not correlated with the grade of DCIS (χ(2) = 9.12, P = 0.16). In the five cases of grade 1 IDC, FAS immunostaining showed that 4 cases were strongly positive and 1 positive; in the 40 cases of grade 2 IDC, FAS immunostaining showed that 27 strongly positive, 12 positive, and 1 negative; in the 15 cases of grade 3 IDC, FAS immunostaining showed that 6 were strongly positive, 5 positive, 3 weakly positive, and 1 negative; FAS expression was stronger and more extensive in DCIS, IDC grades 1 and 2 than that in other groups. However, FAS expression was weaker in the IDC grade 3 (χ(2) = 11.26, P = 0.01). The positive expression rate of FAS in IDC was generally higher than that in benign breast lesions (χ(2) = 47.19, P < 0.01). In the 60 cases of IDC, FISH showed HER2 gene amplification in 22 cases, but not in the remaining 38 cases. FAS expression in IDC was highly correlated with HER2 gene amplification (r = 0.44, P < 0.01). The expression of FAS had significant correlation with status of ER and PR and tumor size (P < 0.05). There was no significant correlation with age, immunohistochemical HER2 expression, lymph node metastasis and clinical stage (P > 0.05).

CONCLUSIONS: FAS may be closely related to the carcinogenesis of breast IDC. FAS expression is closely associated with HER2 gene amplification in IDC.}, } @article {pmid23927337, year = {2013}, author = {Kalluri, KS and Mahd, M and Glick, SJ}, title = {Investigation of energy weighting using an energy discriminating photon counting detector for breast CT.}, journal = {Medical physics}, volume = {40}, number = {8}, pages = {081923}, pmid = {23927337}, issn = {2473-4209}, support = {R01 CA140400/CA/NCI NIH HHS/United States ; }, mesh = {*Breast ; Calcinosis/diagnostic imaging ; Carcinoma, Ductal/diagnostic imaging ; Durapatite/metabolism ; Image Processing, Computer-Assisted ; Mammography/*instrumentation ; Phantoms, Imaging ; *Photons ; Scintillation Counting/*instrumentation ; Signal-To-Noise Ratio ; Tomography, X-Ray Computed/*instrumentation ; }, abstract = {PURPOSE: Breast CT is an emerging imaging technique that can portray the breast in 3D and improve visualization of important diagnostic features. Early clinical studies have suggested that breast CT has sufficient spatial and contrast resolution for accurate detection of masses and microcalcifications in the breast, reducing structural overlap that is often a limiting factor in reading mammographic images. For a number of reasons, image quality in breast CT may be improved by use of an energy resolving photon counting detector. In this study, the authors investigate the improvements in image quality obtained when using energy weighting with an energy resolving photon counting detector as compared to that with a conventional energy integrating detector.

METHODS: Using computer simulation, realistic CT images of multiple breast phantoms were generated. The simulation modeled a prototype breast CT system using an amorphous silicon (a-Si), CsI based energy integrating detector with different x-ray spectra, and a hypothetical, ideal CZT based photon counting detector with capability of energy discrimination. Three biological signals of interest were modeled as spherical lesions and inserted into breast phantoms; hydroxyapatite (HA) to represent microcalcification, infiltrating ductal carcinoma (IDC), and iodine enhanced infiltrating ductal carcinoma (IIDC). Signal-to-noise ratio (SNR) of these three lesions was measured from the CT reconstructions. In addition, a psychophysical study was conducted to evaluate observer performance in detecting microcalcifications embedded into a realistic anthropomorphic breast phantom.

RESULTS: In the energy range tested, improvements in SNR with a photon counting detector using energy weighting was higher (than the energy integrating detector method) by 30%-63% and 4%-34%, for HA and IDC lesions and 12%-30% (with Al filtration) and 32%-38% (with Ce filtration) for the IIDC lesion, respectively. The average area under the receiver operating characteristic curve (AUC) for detection of microcalcifications was higher by greater than 19% (for the different energy weighting methods tested) as compared to the AUC obtained with an energy integrating detector.

CONCLUSIONS: This study showed that breast CT with a CZT photon counting detector using energy weighting can provide improvements in pixel SNR, and detectability of microcalcifications as compared to that with a conventional energy integrating detector. Since a number of degrading physical factors were not modeled into the photon counting detector, this improvement should be considered as an upper bound on achievable performance.}, } @article {pmid23925582, year = {2015}, author = {Zengel, B and Yararbas, U and Duran, A and Uslu, A and Elıyatkın, N and Demırkıran, MA and Cengiz, F and Şimşek, C and Postacı, H and Vardar, E and Durusoy, R}, title = {Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {22}, number = {4}, pages = {374-381}, doi = {10.1007/s12282-013-0489-8}, pmid = {23925582}, issn = {1880-4233}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated.

METHODS: A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach.

RESULTS: The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %).

CONCLUSIONS: MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.}, } @article {pmid23917522, year = {2014}, author = {Patange, A and Thomas, R and Ross, RD}, title = {Severity of mitral regurgitation predicts risk of death or cardiac transplantation in children with idiopathic dilated cardiomyopathy.}, journal = {Pediatric cardiology}, volume = {35}, number = {2}, pages = {232-238}, pmid = {23917522}, issn = {1432-1971}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*complications/mortality/surgery ; Child ; Child, Preschool ; Death, Sudden, Cardiac/*epidemiology/etiology ; Echocardiography ; Female ; Follow-Up Studies ; Forecasting ; *Heart Transplantation ; Humans ; Incidence ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging, Cine ; Male ; Mitral Valve Insufficiency/complications/*diagnosis/surgery ; Prognosis ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate/trends ; United States/epidemiology ; }, abstract = {Clinical outcomes among children with idiopathic dilated cardiomyopathy (IDC) are diverse, which makes the decision as to when a patient should be listed for a cardiac transplantation challenging. This study aimed to determine echocardiographic and clinical variables that can help clinicians identify those at highest risk for death or cardiac transplantation. The study was a single-center, retrospective chart review of children with IDC. Patients younger than 18 years with a diagnosis of IDC, as defined by a left ventricular end-diastolic dimension (LVEDD) z-score higher than 2, and fractional shortening of less than 28 % on the initial echocardiogram, were included in the study. Echocardiographic parameters including mitral regurgitation (MR) grade and certain clinical parameters at the time of presentation were assessed. A follow-up echocardiogram was similarly studied. The study included 49 children with IDC. Those who died or underwent cardiac transplantation were grouped as "nonsurvivors" (n = 26). The remaining children who either completely recovered or experienced chronic dilated cardiomyopathy were grouped as "survivors" (n = 23). The median age overall was 1.25 years (range 0.1-17 years). The follow-up echocardiograms of the survivors showed significant improvement in left ventricle size, systolic function, left atrial volume, and MR grade, whereas these parameters did not change in the nonsurvivor group. The use of inotropic medications at initial presentation was an independent predictor of death or cardiac transplantation (p < 0.05). The presence of moderate to severe MR at diagnosis also was predictive of a worse outcome.}, } @article {pmid23912363, year = {2013}, author = {Freitas, R and Siqueira, LB and Carrijo, EN and Lacerda, RP and Paulinelli, RR and Rahal, RM and Oliveira, LF}, title = {Temporal variation of breast cancer surgical treatment in a university hospital in Brazil's Central West region.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {40}, number = {3}, pages = {180-185}, doi = {10.1590/s0100-69912013000300003}, pmid = {23912363}, issn = {1809-4546}, mesh = {Brazil ; Breast Neoplasms/*surgery ; Cohort Studies ; Cross-Sectional Studies ; Hospitals, University ; Humans ; Mastectomy/*methods/*trends ; Middle Aged ; Retrospective Studies ; Time Factors ; }, abstract = {OBJECTIVE: To assess the types of surgical treatments for breast cancer performed by the Mastology program of the Clinics Hospital, Federal University of Goiás (HC-UFG).

METHODS: We conducted a cross-sectional, cohort study on the breast operations performed at HC-UFG from January 2002 to December 2009. We evaluated the surgical records for: surgical time and size, surgeon, type of operation, diagnosis, and type of anesthesia. The medical charts were researched for: pathology report of the tumor, lymph node involvement, primary tumor size, staging and performance of neoadjuvant therapies. We excluded operations for the removal of benign breast tumors. The temporal variation was analyzed using Poisson regression, considering the annual percentage change (APC).

RESULTS: 403 operations were performed for breast cancer during the study period, with an average of 50.38 operations per year. The most common histological type was invasive ductal carcinoma (72.6%). The mean age of patients was 52 years, and 29% had disease in stages III and IV. The temporal trend revealed a significant increase in tumor size (p <0.01), the clinical stages III and IV (p = 0.01) and the use of neoadjuvant chemotherapy (p = 0.02). There was increase in mastectomies (APC = 9 cases/year, p = .04). There was no increase in cases of breast conservation treatments or of mastectomies with immediate reconstruction.

CONCLUSION: In recent years, the HC-UFG has had an increased number of mastectomies as a result of increased incidence of locoregionally advanced breast cancer.}, } @article {pmid23911773, year = {2013}, author = {Tamaki, K and Tamaki, N and Kamada, Y and Uehara, K and Miyashita, M and Ishida, T and Sasano, H}, title = {A non-invasive modality: the US virtual touch tissue quantification (VTTQ) for evaluation of breast cancer.}, journal = {Japanese journal of clinical oncology}, volume = {43}, number = {9}, pages = {889-895}, doi = {10.1093/jjco/hyt098}, pmid = {23911773}, issn = {1465-3621}, mesh = {Adenocarcinoma, Mucinous/pathology ; Adult ; Aged ; Breast/chemistry/*pathology ; Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Papillary/pathology ; Diagnosis, Differential ; *Elasticity Imaging Techniques ; Female ; Fibroadenoma/pathology ; Humans ; Linear Models ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; *Touch ; *User-Computer Interface ; }, abstract = {OBJECTIVE: We evaluated the biologic features of breast tissues using a newly developed non-invasive diagnostic system, named virtual touch tissue quantification.

METHODS: A total of 180 patients including 115 invasive ductal carcinoma, 30 ductal carcinoma in situ, 4 mucinous carcinoma, 7 invasive lobular carcinoma, 8 fibroadenoma, 12 fibrocystic change and 4 intraductal papilloma were studied at Nahanishi Clinic, Okinawa. We first compared the results of virtual touch tissue quantification according to each histologic subtype and determined the optimal cutoff values for virtual touch tissue quantification to distinguish benign from malignant tissues, using the receiver operating characteristic method. In addition, we also examined the correlation between virtual touch tissue quantification velocities and Ki-67, estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 in cases of invasive ductal carcinoma using linear regression analyses and Student's t-test.

RESULTS: Virtual touch tissue quantification velocities were statistically higher in malignant cases than in benign cases (P < 0.05, respectively) and the best cutoff value for the virtual touch tissue quantification velocity which could differentiate benign from malignant cases was 2.89 m/s. There were statistically significant correlations between the virtual touch tissue quantification velocity and the Ki-67 labeling index (r = 0.338, r(2) = 0.114 and P < 0.001) and significant inverse correlations between virtual touch tissue quantification and the estrogen receptor (r = -0.311, r(2) = 0.097 and P < 0.001) or progesterone receptor (r = -0.361, r(2) = 0.131 and P < 0.001) status of invasive ductal carcinoma. There were also significant differences of the average velocities between human epidermal growth factor receptor 2-positive (6.39 ± 1.44 m/s) and -negative (4.43 ± 1.41 m/s) cases (P < 0.001).

CONCLUSION: Virtual touch tissue quantification could be a valuable clinical tool for estimating breast cancer pathology in a non-invasive fashion.}, } @article {pmid23910495, year = {2013}, author = {Guilbert, A and Gautier, M and Dhennin-Duthille, I and Rybarczyk, P and Sahni, J and Sevestre, H and Scharenberg, AM and Ouadid-Ahidouch, H}, title = {Transient receptor potential melastatin 7 is involved in oestrogen receptor-negative metastatic breast cancer cells migration through its kinase domain.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {49}, number = {17}, pages = {3694-3707}, doi = {10.1016/j.ejca.2013.07.008}, pmid = {23910495}, issn = {1879-0852}, mesh = {Breast Neoplasms/*genetics/*pathology ; Calcium/metabolism ; Cell Movement/drug effects/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Metastasis ; Phosphotransferases/chemistry/physiology ; Protein Structure, Tertiary/physiology ; RNA, Small Interfering/pharmacology ; Receptors, Estrogen/metabolism ; TRPM Cation Channels/antagonists & inhibitors/chemistry/*physiology ; Tumor Cells, Cultured ; }, abstract = {Oestrogen receptor negative (ER(-)) invasive ductal carcinoma (IDC) represents a significant clinical challenge and therefore prompts the discovery of novel biomarkers. Transient receptor potential melastatin 7 (TRPM7), a channel protein that also contains a regulatory kinase domain, is overexpressed in IDC and regulates migration. However, the molecular mechanism remains poorly defined. Here, we examined whether TRPM7 regulates migration by its channel function or by its kinase domain. A Magnesium Inhibited Cation current was recorded in two ER(-) highly metastatic breast cancer cell lines. Down-regulation of TRPM7 neither affected Ca(2+)-, nor Mg(2+)-homoeostasis but significantly reduced cell migration via a Ca(2+)-independent pathway. Notably, the overexpression of the truncated kinase domain form of TRPM7 decreased cell migration, while the overexpression of the wild-type form strongly increased it. Concomitantly, TRPM7 silencing reduced the myosin IIA heavy chain phosphorylation. Furthermore, we found higher TRPM7 expression in ER(-) IDC tissues and lymph nodes than in the non-invasive tumoural samples. In conclusion, TRPM7 plays a critical role in breast cancer cell migration through its kinase domain, and our data support the consideration of using TRPM7 as a novel biomarker and a potential therapeutic target in the treatment of human ER(-) IDC.}, } @article {pmid23909745, year = {2014}, author = {Pardess, E and Mikulincer, M and Dekel, R and Shaver, PR}, title = {Dispositional attachment orientations, contextual variations in attachment security, and compassion fatigue among volunteers working with traumatized individuals.}, journal = {Journal of personality}, volume = {82}, number = {5}, pages = {355-366}, doi = {10.1111/jopy.12060}, pmid = {23909745}, issn = {1467-6494}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Fatigue/epidemiology/*psychology ; Female ; *Helping Behavior ; Humans ; *Interpersonal Relations ; Israel ; Male ; Middle Aged ; *Object Attachment ; Stress Disorders, Post-Traumatic/*psychology/therapy ; Volunteers/*psychology/statistics & numerical data ; Young Adult ; }, abstract = {In the present article, we report a series of studies examining the links between attachment orientations and compassion fatigue among volunteers working with traumatized individuals. Participants were volunteers in several trauma-related organizations, ranging in age from 18 to 69 years. In Study 1 (N = 148), we examined associations between self-reports of attachment insecurities and compassion fatigue. In Study 2 (N = 54), we used a diary design to assess attachment-related differences in emotional reactions to actual helping encounters over a 2-month period. In Study 3 (N = 108), we examined the effects of the experimental enhancement of attachment security (security priming) on reactions to a hypothetical helping encounter. As expected, attachment insecurities, either anxiety or avoidance, were associated with heightened compassion fatigue. Moreover, security priming reduced compassion fatigue in response to a hypothetical helping encounter. These findings underscore the relevance of attachment theory for understanding and preventing compassion fatigue.}, } @article {pmid23907150, year = {2014}, author = {Khoury, T and Hu, Q and Liu, S and Wang, J}, title = {Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {27}, number = {2}, pages = {194-203}, pmid = {23907150}, issn = {1530-0285}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/classification/*genetics/pathology ; Carcinoma, Ductal, Breast/classification/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/classification/*genetics/pathology ; Carcinoma, Papillary/classification/*genetics/pathology ; Cluster Analysis ; Comparative Genomic Hybridization ; Female ; Gene Dosage ; Humans ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1-23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.}, } @article {pmid23907124, year = {2013}, author = {Martins, D and Beça, FF and Sousa, B and Baltazar, F and Paredes, J and Schmitt, F}, title = {Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma: key events in the progression from an in situ to an invasive breast carcinoma.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {12}, number = {16}, pages = {2684-2690}, pmid = {23907124}, issn = {1551-4005}, mesh = {Breast Neoplasms/*physiopathology ; Caveolin 1/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunohistochemistry ; Monocarboxylic Acid Transporters/*metabolism ; Muscle Proteins/*metabolism ; Neoplasm Invasiveness/*physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {The progression from in situ to invasive breast carcinoma is still an event poorly understood. However, it has been suggested that interactions between the neoplastic cells and the tumor microenvironment may play an important role in this process. Thus, the determination of differential tumor-stromal metabolic interactions could be an important step in invasiveness. The expression of stromal Caveolin-1 (Cav-1) has already been implicated in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Additionally, stromal Cav-1 expression has been associated with the expression of stromal monocarboxylate transporter 4 (MCT4) in invasive breast cancer. However, the role of stromal MCT4 in invasiveness has never been explored, neither the association between Cav-1 and MCT4 in the transition from breast DCIS to IDC. Therefore, our aim was to investigate in a series of breast cancer samples including matched in situ and invasive components, if there was a relationship between stromal Cav-1 and MCT4 in the progression from in situ to invasive carcinoma. We found loss of stromal Cav-1 in the progression to IDC in 75% of the cases. In contrast, MCT4 stromal expression was acquired in 87% of the IDCs. Interestingly, a concomitant loss of Cav-1 and gain of MCT4 was observed in the stroma of 75% of the cases, when matched in situ and invasive carcinomas were compared. These results suggest that alterations in Cav-1 and MCT4 may thus mark a critical point in the progression from in situ to invasive breast cancer.}, } @article {pmid23901713, year = {2013}, author = {Aytac, B and Sahsine, T and Erturk, FY and Kahveci, R and Gokgoz, S}, title = {Evaluation of incidence and histolopathological findings of breast lesions in reduction mammoplasty specimens: Uludag University experience.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {63}, number = {7}, pages = {878-881}, pmid = {23901713}, issn = {0030-9982}, mesh = {Adolescent ; Adult ; Age Distribution ; Breast/*pathology/*surgery ; Breast Diseases/epidemiology/*pathology ; Female ; *Hospitals, University ; Humans ; Incidence ; *Mammaplasty ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Turkey/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To report the incidence of benign, pre-cancerous and malignant lesions in reduction mammoplasty specimens.

METHODS: The retrospective study was conducted at the Uludag University, Bursa, Turkey and comprised data of 264 patients who underwent bilateral breast reduction between 2004 and 2009. Operative reports and pathological findings of all patients were reviewed. Patients were divided into three age groups with reference to the hormonal characteristics: girls and women between 13 and 35 years constituted group 1; women older than 35 and younger than 50 years old were clustered in group 2; and women over 50 years formed group 3. Descriptive statistics were applied.

RESULTS: Fibrocystic disease was the most common (n=402; 76.13%) lesion in all groups. Proliferative lesions such as intraductal epithelial hyperplasia and atypical ductal hyperplasia were each found in 0.4% (n=2) cases. There were 2(0.4%) cases with invasive ductal carcinoma, and 1(0.2%) case with ductal carcinoma in situ. All malignant tumours were found in patients over 50 years of age.

CONCLUSION: Microscopic examination of macroscopically normal breast tissue from breast reduction specimens may provide noteworthy pathological findings. Histological sampling of reduction mammoplasty specimens gave rise to the early detection of occult neoplastic breast lesions.}, } @article {pmid23899963, year = {2014}, author = {Maschio, LB and Madallozo, BB and Capellasso, BA and Jardim, BV and Moschetta, MG and Jampietro, J and Soares, FA and Zuccari, DA}, title = {Immunohistochemical investigation of the angiogenic proteins VEGF, HIF-1α and CD34 in invasive ductal carcinoma of the breast.}, journal = {Acta histochemica}, volume = {116}, number = {1}, pages = {148-157}, doi = {10.1016/j.acthis.2013.06.005}, pmid = {23899963}, issn = {1618-0372}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; ROC Curve ; Tissue Array Analysis ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {The expression of prognostic markers in cancer has become important in diagnostic routine and research. A high mitotic rate compromises the individual cell access to oxygen and nutrients, due to reduced blood supply. Cells undertake adaptive measures such as vascular endothelial growth factor (VEGF), expressed under the control of hypoxia-inducible factor-1α (HIF-1α). CD34 is an endothelial marker which can show the presence and distribution of blood vessels. This study evaluated the presence and relative expression of VEGF, HIF-1α and CD34 using immunohistochemistry of 60 breast tumors and double staining, correlating the findings with clinical and pathological variables. High VEGF expression was correlated with low cell proliferation, lymph node-negative, smaller tumor size and patients not receiving hormone therapy. High HIF-1α expression predominated in younger (<50-year) patients, subjected to neo-adjuvant therapy and in p53-negative tumors. Absence of metastasis, radiotherapy or hormone treatment, and estrogen receptor (ER)-positive tumors showed high CD34 immunoreactivity. We suggest that the angiogenic factors VEGF, HIF-1α and CD34 are important in breast cancer progression and their abundance in breast tumors has prognostic and predictive value.}, } @article {pmid23891136, year = {2013}, author = {Amin, M and Radkay, L and Pantanowitz, L and Fine, J and Parwani, A}, title = {Tumor-to-tumor metastasis (TTM) of breast carcinoma within a solitary renal angiomyolipoma: a case report.}, journal = {Pathology, research and practice}, volume = {209}, number = {9}, pages = {605-608}, doi = {10.1016/j.prp.2013.06.011}, pmid = {23891136}, issn = {1618-0631}, mesh = {Aged ; Angiomyolipoma/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Female ; Humans ; Kidney Neoplasms/*pathology/secondary ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {Angiomyolipomas of the kidney have been known to harbor malignant neoplasms including renal cell carcinoma. We report a case of a tumor-to-tumor metastasis (TTM) involving metastatic breast carcinoma and angiomyolipoma. The patient was a 67-year-old female with a history of invasive ductal carcinoma of the breast. Follow-up positron emission tomography 9 years later revealed a left renal mass, suspicious for a primary renal neoplasm, as well as a suspicious subpectoral lymph node. An ultrasound-guided needle biopsy of the lymph node demonstrated metastatic breast carcinoma. The patient underwent a left radical nephrectomy. Pathologic examination demonstrated an ill-defined 2cm estrogen receptor (ER)-positive metastatic breast carcinoma within a 6cm angiomyolipoma. To our knowledge, this is the first reported case of metastatic breast carcinoma to a solitary renal angiomyolipoma. This case highlights the importance of a patient's prior history of malignancy, as well as appropriate sampling of renal neoplasms.}, } @article {pmid23886168, year = {2013}, author = {Panahi, M and Saki, N and Ashourzadeh, S and Rahim, F}, title = {Expressional correlation of human epidermal growth factor receptor 2, estrogen/progesterone receptor and protein 53 in breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {14}, number = {6}, pages = {3699-3703}, doi = {10.7314/apjcp.2013.14.6.3699}, pmid = {23886168}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Medullary/metabolism/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: This study aimed to show the localization of estrogen / progesterone receptors, human epidermal growth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breast cancer patients.

MATERIALS AND METHODS: The study covered invasive breast cancers from 299 patients presenting at the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospital in Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used.

RESULTS: Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 years old. The highest incidence of breast cancer in this study population was in the group of more than 50 year age, and the most common histological type of breast cancer was the invasive ductal carcinoma, which accounted for 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) were scored as grade ?, ??, ???, respectively.

CONCLUSION: Our findings demonstrated a lack of association between labeling for the markers studied and tumor size and age of the patients. We confirmed an association between ER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature be because of differences in the immunohistochemical techniques applied in the various studies and to the scoring systems used.}, } @article {pmid23883300, year = {2013}, author = {Wang, S and Zhang, Y and Yang, X and Fan, L and Qi, X and Chen, Q and Jiang, J}, title = {Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors.}, journal = {World journal of surgical oncology}, volume = {11}, number = {1}, pages = {166}, pmid = {23883300}, issn = {1477-7819}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Epirubicin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Recurrence, Local/*drug therapy/metabolism/pathology ; Neoplasm Staging ; Neoplasm, Residual/*drug therapy/metabolism/pathology ; Paclitaxel/administration & dosage ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Breast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients' quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT.

METHODS: Ninety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining.

RESULTS: The residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2.

CONCLUSION: Three types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.}, } @article {pmid23879372, year = {2014}, author = {Tuomainen, PO and Magga, J and Fedacko, J and Kärkkäinen, S and Miettinen, K and Vanninen, E and Kuusisto, J and Peuhkurinen, KJ}, title = {Idiopathic dilated cardiomyopathy and chronic atrial fibrillation.}, journal = {Clinical physiology and functional imaging}, volume = {34}, number = {2}, pages = {133-137}, doi = {10.1111/cpf.12075}, pmid = {23879372}, issn = {1475-097X}, mesh = {Adolescent ; Adult ; Aged ; Arterial Pressure ; Atrial Fibrillation/blood/diagnosis/*etiology/physiopathology ; Biomarkers/blood ; Cardiomyopathy, Dilated/blood/*complications/diagnosis/*physiopathology ; Chronic Disease ; Female ; Heart Atria/diagnostic imaging ; Heart Ventricles/diagnostic imaging/physiopathology ; Humans ; Interleukin-6/blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Pulmonary Artery/physiopathology ; Pulmonary Wedge Pressure ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; Ultrasonography ; Ventricular Function, Left ; Young Adult ; }, abstract = {BACKGROUND: Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR).

METHODS: A group of patients with IDC underwent extensive non-invasive and invasive evaluation during a hospitalization period. The patients were further divided into two groups with AF (n = 19) and SR (n = 68).

RESULTS: Left atrial diameter was greater (P<0·001), left ventricular end-diastolic diameter smaller (P<0·05), left ventricular end-diastolic and end-systolic volumes smaller (P<0·01 for all), mean pulmonary artery pressure and pulmonary capillary wedge pressure higher (P<0·05 for both), cardiac output and maximal oxygen consumption lower (P<0·01 and P<0·05, respectively), and the levels of N-terminal pro-brain natriuretic peptide and interleukin-6 higher (P<0·05 for both) in AF group compared with SR group. Left ventricular ejection fraction and left ventricular end-diastolic pressure were similar in both groups.

CONCLUSIONS: In spite of otherwise more unfavourable prognostic factor profile, left ventricular size was observed to be smaller in chronic AF compared with SR in well-characterized patients with IDC. The confirmation and possible explainers of this paradoxical phenomenon need further studies in larger patient cohorts.}, } @article {pmid23870857, year = {2013}, author = {Kim, JY and Han, W and Moon, HG and Park, IA and Ahn, SK and Kim, J and Lee, JW and Kim, T and Kim, MK and Noh, DY}, title = {Grade of ductal carcinoma in situ accompanying infiltrating ductal carcinoma as an independent prognostic factor.}, journal = {Clinical breast cancer}, volume = {13}, number = {5}, pages = {385-391}, doi = {10.1016/j.clbc.2013.04.005}, pmid = {23870857}, issn = {1938-0666}, mesh = {Adult ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: Several studies about the relationship between IDC and DCIS have been reported, but no consensus has been reached regarding clinical characteristics and prognostic value.

PATIENTS AND METHODS: We reviewed the medical records of patients who underwent surgery for IDC between 2006 and 2008. DCIS adjacent to IDC was pathologically classified as either high-grade DCIS or non-high-grade DCIS.

RESULTS: Among 1751 IDC patients within the study period, 1384 patients (79.0%) had concomitant DCIS. There was no survival difference between patients with pure IDC and those with IDC and concomitant DCIS. However, patients with high-grade DCIS had worse survival than did patients with non-high-grade DCIS or pure IDC (5-year recurrence-free survival rates for IDC with non-high-grade DCIS, pure IDC without DCIS, and IDC with high-grade DCIS were 97%, 93%, and 86%, respectively; P = .001). This tendency was maintained regardless of estrogen receptor status or histologic grade of IDC. In a Cox regression model, patients with IDC and accompanying high-grade DCIS had a 2.5-fold higher probability of local or distant relapse than did those with IDC and low-grade DCIS (hazard ratio, 2.51; 95% confidence interval, 1.12-5.64).

CONCLUSIONS: The prognosis of patients with invasive breast cancer differed according to the grade of concomitant adjacent DCIS. Accordingly, the grade of adjacent DCIS should be considered as a prognostic factor in the clinical management of patients with breast cancer. However, in our study, the follow-up periods were short to confirm prognostic effect. Further studies are needed.}, } @article {pmid23870824, year = {2013}, author = {Kis-Toth, K and Bacskai, I and Gogolak, P and Mazlo, A and Szatmari, I and Rajnavolgyi, E}, title = {Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001.}, journal = {Immunobiology}, volume = {218}, number = {11}, pages = {1361-1369}, doi = {10.1016/j.imbio.2013.06.012}, pmid = {23870824}, issn = {1878-3279}, mesh = {Antigens, CD1/metabolism ; Cell Differentiation/immunology ; Cell Movement/*drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*immunology ; Dipeptides/*pharmacology ; Humans ; Inflammation/*immunology ; Matrix Metalloproteinase 12/biosynthesis/metabolism ; Matrix Metalloproteinase 9/biosynthesis/metabolism ; Matrix Metalloproteinase Inhibitors/*pharmacology ; Monocytes ; Tissue Inhibitor of Metalloproteinase-1/biosynthesis/metabolism ; Tissue Inhibitor of Metalloproteinase-2/biosynthesis/metabolism ; }, abstract = {Matrix metalloproteinases (MMPs) are endopeptidases with the potential to cleave extracellular matrix, support tissue renewal and regulate cell migration. Functional activities of MMPs are regulated by tissue inhibitors of MMPs (TIMPs) and disruption of the MMP-TIMP balance has pathological consequences. Here we studied the expression and secretion of MMPs and TIMPs in CD1a(-) and CD1a(+) monocyte-derived dendritic cell (DC) subpopulations. Our results showed that monocytes express TIMPs but lack MMPs, whereas upon differentiation to moDCs and in response to activation signals the expression of MMPs is increased and that of TIMPs is decreased. MMP-9 is expressed dominantly in the CD1a(-) subpopulation, while MMP-12 is preferentially expressed in CD1a(+) cells. Experiments performed with the synthetic MMP inhibitor GM6001 revealed that this drug efficiently inhibits the migration of moDCs through inactivation of MMPs. We conclude that modulation of MMP activity by GM6001 emerges as a novel approach to manipulate DC migration under inflammatory conditions.}, } @article {pmid23863867, year = {2013}, author = {Korhonen, T and Kuukasjärvi, T and Huhtala, H and Alarmo, EL and Holli, K and Kallioniemi, A and Pylkkänen, L}, title = {The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {6}, pages = {1119-1124}, doi = {10.1016/j.breast.2013.06.001}, pmid = {23863867}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Carcinoma, Lobular/*pathology/*secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*pathology ; Proportional Hazards Models ; Skin Neoplasms/secondary ; Survival Rate ; }, abstract = {The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan-Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant. Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up.}, } @article {pmid23863656, year = {2013}, author = {Matsuda, T and Fujita, H and Kunimoto, Y and Hosono, M and Kimura, T and Hayashi, T and Maeda, T and Yamakawa, J and Maeda, N and Mizumoto, T and Maruyama, S and Uenaka, Y and Ogino, K}, title = {[Successful ventilator weaning by trastuzumab in a HER2-positive breast cancer patient with multiple lung metastases].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {6}, pages = {773-776}, pmid = {23863656}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Female ; Humans ; Lung Neoplasms/*drug therapy/secondary ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Trastuzumab ; Ventilator Weaning ; }, abstract = {We report a case of breast cancer with severe respiratory dysfunction due to multiple lung metastases, which was recovered by treatment with weekly trastuzumab administration. A 47-year-old woman with breast cancer had received a folk remedy from a general practitioner for 4 years. However, she was delivered to a hospital because of severe dyspnea, and intubation was found to be needed and performed. She was diagnosed with left breast cancer with skin and pleural wall invasion, and multiple lung metastases. Pathological examination showed invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive. After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory function improved gradually, and ventilator weaning was successful at 53 days after trastuzumab administration. CT examination also showed a remarkable reduction of lung and lymph node metastases and pleural effusion. She was discharged from our hospital 80 days after treatment, and her treatment with trastuzumab and capecitabine has been ongoing at an outpatient clinic.}, } @article {pmid23863654, year = {2013}, author = {Kobayashi, T and Matsuda, Y and Azama, T}, title = {[A case of a patient with breast cancer, diagnosed from sternal metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {6}, pages = {765-767}, pmid = {23863654}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/*drug therapy/secondary ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration & dosage ; Carcinoma, Ductal, Breast/pathology/*therapy ; Chemoradiotherapy ; Cyclophosphamide/administration & dosage ; Epirubicin/administration & dosage ; Female ; Humans ; Mastectomy, Segmental ; Neoplasm Staging ; Sternum/*pathology ; Taxoids/administration & dosage ; }, abstract = {A 32-year-old woman was seen in our hospital for complaints of bulge and pain in the sternum, and upon examination showed a lump in the left breast and enlarged left axillary lymph nodes. The patient was diagnosed with invasive ductal carcinoma with metastasis to the sternum that was T2N1M1(OSS), Stage IV, hormone-receptor-positive, and HER2-negative. Four courses each of EC and taxane therapy were performed as primary systemic chemotherapy in combination with zoledronic acid, which resulted in calcification of the osteolytic lesion in the sternum and reduced tumor mass in the breast. The patient was judged to have a partial response(PR)to the treatment. Eight months later, breast-conserving surgery and axillary lymph node dissection were performed, followed by radiation therapy to the left breast and sternum. Treatment with zoledronicac id is ongoing and postoperative hormonal therapy has been started. Four years and 4 months after the initial diagnosis, the lesion in the sternum has calcified and hardened and the patient has not had a recurrence in the same breast or elsewhere in the body.}, } @article {pmid23863653, year = {2013}, author = {Morishita, A and Mitsuhashi, S and Fujisawa, F and Hirano, M and Kojima, H}, title = {[Usefulness of bevacizumab with paclitaxel for advanced breast cancer - a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {6}, pages = {761-764}, pmid = {23863653}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Lung Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel/administration & dosage ; Tomography, X-Ray Computed ; }, abstract = {A 55-year-old woman with an exudative, necrotizing left breast tumor consulted Ibaraki Prefectural Central Hospital and Cancer Center. We diagnosed her as advanced ER+, PgR-, HER2- invasive ductal carcinoma of the left breast by tumor needle biopsy. FDG-PET/CT revealed multiple lymph node, pulmonary, bone, and hepatic metastases. Systemic chemotherapy with biweekly bevacizumab and weekly paclitaxel(PTX)was administered. The chemotherapy induced a widespread tumor lysis in her left chest wall. We continued chemotherapy, and the ulcer has been healing gradually. We recognized that bevacizumab with PTX successfully brought about a rapid, good local response, and improved the patient's quality of life.}, } @article {pmid23863587, year = {2013}, author = {Yoshibayashi, H and Ishiguro, H and Kawaguchi, K and Yamoto, M and Nishimura, T and Yamada, H and Namura, M and Nishio, N and Nakamura, K and Shimada, K and Ono, K and Kato, H}, title = {[A patient with primary breast cancer who responded remarkably well to neoadjuvant chemotherapy with FEC100 followed by Abraxane].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {40}, number = {5}, pages = {627-629}, pmid = {23863587}, issn = {0385-0684}, mesh = {Albumin-Bound Paclitaxel ; Albumins/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Paclitaxel/administration & dosage ; }, abstract = {A 49-year-old woman visited our hospital presentind with a right breast lump. She underwent core needle biopsy, and her disease was diagnosed as breast cancer(invasive ductal carcinoma, ER slightly positive, PgR and HER2 negative). We chose neoadjuvant chemotherapy because the tumor size was over 3 cm in diameter with a histological grade III, and she asked to have her breast conserved. Because she had an allergy to alcohol, we treated her with FEC100 followed by Abraxane(260mg/ m2)q3W for 4 courses. After chemotherapy, she received breast conserving therapy. During the treatment with Abraxane, the patient was very well and showed no major side effects except for grade 3 neutropenia was found on an outpatient basis. After chemotherapy, breast MRI detected no invasive lesion. Pathological examination showed pCR. We concluded that Abraxane was a good option as neoadjuvant chemotherapy for early breast cancer.}, } @article {pmid23857151, year = {2013}, author = {Kamitani, T and Matsuo, Y and Yabuuchi, H and Fujita, N and Nagao, M and Jinnouchi, M and Yonezawa, M and Yamasaki, Y and Tokunaga, E and Kubo, M and Yamamoto, H and Yoshiura, T and Honda, H}, title = {Correlations between apparent diffusion coefficient values and prognostic factors of breast cancer.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {12}, number = {3}, pages = {193-199}, doi = {10.2463/mrms.2012-0095}, pmid = {23857151}, issn = {1880-2206}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/*epidemiology/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Japan/epidemiology ; Middle Aged ; Prevalence ; Prognosis ; Reproducibility of Results ; Risk Assessment ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {PURPOSE: We investigated possible correlations between apparent diffusion coefficient (ADC) values and prognostic factors of breast cancer.

METHODS: We retrospectively evaluated 81 patients who underwent magnetic resonance (MR) imaging of the breast and were diagnosed pathologically with invasive ductal carcinoma (IDC) not otherwise specified with invasive foci one cm or larger. We excluded ductal carcinoma in situ and IDC with invasive foci smaller than one cm because small lesions decrease the reliability of signal intensity of diffusion-weighted imaging (DWI). We also excluded special type cancers. We used t-test to compare the mean ADC values of cancers of Stage pT1 (≤2 cm) versus pT2 or 3 (>2 cm), cancers with versus without vascular invasion, axillary lymph node (N)-positive versus N-negative cancers, estrogen receptor (ER)-positive versus ER-negative cancers, and progesterone receptor (PgR)-positive versus PgR-negative cancers. We analyzed correlations between the ADC value with nuclear grade (NG) and human epidermal growth factor receptor 2 (HER2) score by rank test using Spearman's correlation coefficient.

RESULTS: The mean ADC value was significantly higher for N-positive (n=28; 0.97 ± 0.20 × 10(-3) mm(2)/s) than N-negative cancers (n=53; 0.87 ± 0.17 × 10(-3) mm(2)/s) (P=0.017); significantly lower for ER-positive (n=63; 0.88 ± 0.15 × 10(-3) mm(2)/s) than ER-negative cancers (n=18; 1.01 ± 0.21 × 10(-3) mm(2)/s) (P=0.005); and significantly lower for PgR-positive (n=47; 0.88 ± 0.16 × 10(-3) mm(2)/s) than PgR-negative cancers (n=34; 0.95 ± 0.18 × 10(-3) mm(2)/s) (P=0.048). Tumor size, vascular invasion, NG, and HER2 status showed no significant correlation with ADC values.

CONCLUSION: ADC values were higher for N-positive and ER-negative breast cancers than N-negative and ER-positive cancers.}, } @article {pmid23850271, year = {2013}, author = {Lu, Z and Yong, T and Wen, Y and Yifei, G and Xinwei, W and Lili, Y and Ye, T}, title = {Vesicle consisted of calcified core and intervening turbid fluid, a possible composition of calcification in intervertebral disc calcification in children.}, journal = {Medical hypotheses}, volume = {81}, number = {3}, pages = {503-505}, doi = {10.1016/j.mehy.2013.06.021}, pmid = {23850271}, issn = {1532-2777}, mesh = {Calcinosis/diagnostic imaging/*physiopathology/surgery ; Child ; Humans ; Intervertebral Disc/diagnostic imaging/*physiopathology/surgery ; Secretory Vesicles/*diagnostic imaging ; Tomography, X-Ray Computed ; }, abstract = {Intervertebral disc calcification (IDC) is one of the uncommon diseases in children. Normally, it is a benign lesion which is self-limited and has an excellent prognosis under conservative treatments and symptomatic support. Surgical treatment is usually carried out only for patients with progressive neurological deterioration in order to prevent the spinal cord from being irreversible injured. After conservative treatments for months or years, the calcification reduces gradually or even disappears through imaging. Until now, the etiology remains unclear and the mechanism for resorption of IDC is still unknown. Surgery was performed on an IDC patient with progressive neurological deterioration, it was found that the high density calcification region on CT is actually not "hard" but more like an enlarged cell. In such a cell, a calcified nuclear was surrounded by limewater-like liquid inside a large membrane. This study aims to unveil the mechanism for the resorption of IDC. We hypothesize that the high density calcification on imaging is a vesicle consisted of calcified core and intervening turbid fluid. Furthermore, the increase or diminution of calcification is caused by the production or resorption of inflammatory fluid around the calcified core in lesion disc. This could explain the mechanism of IDC resorption in children.}, } @article {pmid23847668, year = {2013}, author = {Badowska-Kozakiewicz, AM and Sobol, M and Patera, J and Kozłowski, W}, title = {Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women.}, journal = {Archives of medical science : AMS}, volume = {9}, number = {3}, pages = {466-471}, pmid = {23847668}, issn = {1734-1922}, abstract = {INTRODUCTION: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor.

MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO.

RESULTS: Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients.

CONCLUSIONS: Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.}, } @article {pmid23845673, year = {2013}, author = {Higgins, L and Robertson, I and Khan, W and Barry, K}, title = {Synchronous breast and colon cancer: factors determining treatment strategy.}, journal = {BMJ case reports}, volume = {2013}, number = {}, pages = {}, pmid = {23845673}, issn = {1757-790X}, mesh = {Adenocarcinoma/*therapy ; Aged ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Colonic Neoplasms/*therapy ; Female ; Humans ; Neoplasms, Multiple Primary/*therapy ; }, abstract = {A 67-year-old woman presented with synchronous breast and colonic tumours, in the absence of family history. Following multidisciplinary discussion, the patient was started on endocrine therapy for breast cancer. Initial surgical management consisted of right hemicolectomy together with segmental resection of a serosal deposit adherent to the distal ileum, for a moderately differentiated pT4NO caecal carcinoma. Three months later, right mastectomy and axillary clearance confirmed node positive invasive ductal carcinoma. The original treatment plan was to prioritise adjuvant chemotherapy for breast cancer postmastectomy. However, the subsequent CT finding of an enlarged, suspicious mesenteric lymph node mass on repeat staging raised concern regarding its origin. Image-guided biopsy revealed metastatic colonic adenocarcinoma and the patient was switched to a colon cancer chemotherapy regime. Following adjuvant chemotherapy for colonic carcinoma, an en-bloc surgical resection of the enlarging metastatic nodal mass was performed with clear resection margins. The patient is currently asymptomatic.}, } @article {pmid23845572, year = {2013}, author = {Patten, DK and Sharifi, LK and Fazel, M}, title = {New approaches in the management of male breast cancer.}, journal = {Clinical breast cancer}, volume = {13}, number = {5}, pages = {309-314}, doi = {10.1016/j.clbc.2013.04.003}, pmid = {23845572}, issn = {1938-0666}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Axilla/surgery ; Breast Neoplasms, Male/drug therapy/pathology/*therapy ; Female ; Humans ; Male ; Neoplasm Metastasis ; Radiotherapy/methods ; }, abstract = {Male breast cancer (MBC) is a rare condition that accounts for 0.1% of all male cancers. Our current evidence base for treatment is derived from female breast cancer (FBC) patients. Risk factors for MBC include age, genetic predisposition, race, sex hormone exposure, and environmental factors. Most patients present later and with more advanced disease than comparable FBC patients. Tumors are likely to be estrogen receptor and progesterone receptor positive, with the most common histologic type being invasive ductal carcinoma. Triple assessment remains the criterion standard for diagnosis. Primary MBC is mostly managed initially by simple mastectomy, with the option of breast conserving surgery, which carries an increased risk of recurrence. Sentinel node biopsy is recommended as the initial procedure for staging the axilla. Reconstructive surgery focuses on achieving primary skin closure, and radiotherapy largely follows treatment protocols validated in FBC. We recommend chemotherapy for men with more advanced disease, in particular, those with estrogen receptor negative histology. MBC responds well to endocrine therapy, although it is associated with significant adverse effects. Third-generation aromatase inhibitors are promising but raise concerns due to their failure to prevent estrogen synthesis in the testes. Fulvestrant remains unproven as a therapy, and data on trastuzumab is equivocal with HER2 receptor expression and functionality unclear in MBC. In metastatic disease, drug-based hormonal manipulation remains a first-line therapy, followed by systemic chemotherapy for hormone-refractory disease. Prognosis for MBC has improved over the past 30 years, with survival affected by disease staging, histologic classification, and comorbidity.}, } @article {pmid23844308, year = {2013}, author = {Yoshimura, N and Murakami, S and Kaneko, M and Sakatani, A and Hirabayashi, N and Takiyama, W}, title = {Synchronous bilateral solid papillary carcinomas of the breast.}, journal = {Case reports in surgery}, volume = {2013}, number = {}, pages = {812129}, pmid = {23844308}, issn = {2090-6900}, abstract = {We herein report a case of synchronous bilateral solid papillary carcinoma of the breast. A 73-year-old female had a mass that was detected in the right breast on mammography. An ultrasound examination revealed one intracystic tumor in the right breast and two tumors in the left breast. A fine-needle aspiration biopsy of these three tumors was performed, which revealed a diagnosis of malignancy. A magnetic resonance imaging examination of the breasts showed diffuse small nodules surrounding these tumors bilaterally. Bilateral partial mastectomy and a sentinel lymph node biopsy were performed. Lymph node metastasis was detected in the right axilla, and additional lymph node dissection was performed. The pathological diagnosis was synchronous bilateral breast cancer, invasive ductal carcinoma NOS of the right breast, mucinous carcinomas of the left breast, and bilateral SPCs. A wide range of surgical margins were positive for SPCs, and additional bilateral total mastectomy was then performed. To the best of our knowledge, little is known about synchronous bilateral SPCs. Our case indicates that some SPCs can be widely scattered and make up a variety of invasive carcinomas. It is difficult to make a correct preoperative evaluation in such cases.}, } @article {pmid23843846, year = {2013}, author = {Do, SI and Kim, K and Kim, DH and Chae, SW and Park, YL and Park, CH and Sohn, JH}, title = {Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas.}, journal = {Journal of breast cancer}, volume = {16}, number = {2}, pages = {152-158}, pmid = {23843846}, issn = {1738-6756}, abstract = {PURPOSE: Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters.

METHODS: We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry.

RESULTS: MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed.

CONCLUSION: Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.}, } @article {pmid23838905, year = {2013}, author = {Jaffré, I and Campion, L and Dejode, M and Bordes, V and Sagan, C and Loussouarn, D and Dravet, F and Andrieux, N and Classe, JM}, title = {Margin width should not still enforce a systematic surgical re-excision in the conservative treatment of early breast infiltrative ductal carcinoma.}, journal = {Annals of surgical oncology}, volume = {20}, number = {12}, pages = {3831-3838}, doi = {10.1245/s10434-013-3063-x}, pmid = {23838905}, issn = {1534-4681}, mesh = {Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; *Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/mortality/*pathology/surgery ; Neoplasm Staging ; Neoplasm, Residual/mortality/*pathology/surgery ; Prognosis ; Prospective Studies ; *Reoperation ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: In cases where breast conservative surgery was performed for infiltrative ductal carcinoma (IDC), margin status is an independent prognostic factor for local ipsilateral relapse (LIR). There is no validated definition of a clear margin. We investigated factors associated with residual disease on re-excision specimen and the impact of margin status on the risk of LIR.

METHODS: From January 1992 to December 2002, 454 patients were retrospectively included. Patients had undergone conservative surgery and radiotherapy for IDC. Two groups were defined: group 1, involved or close margin (<3 mm) and a re-excision; and group 2, involved or close margin without re-excision. The risk factors for residual disease in the re-excision specimen were analyzed in group 1, and the rate of 5-year LIR was analyzed in both groups.

RESULTS: Among patients who experienced a surgical re-excision for involved or close margin, 21% (55 of 206) had residual tumor. The multivariate analysis showed that only a margin involved with intraductal carcinoma remained predictive for residual disease. According to the multivariate analysis, only hormone therapy (p < 10(-6)), diffuse involved margins (p = 0.003), and margins involved with intraductal component (p < 10(-6)) were predictive of LIR. Re-excision for a margin involved with intraductal carcinoma significantly improved local relapse-free survival (p < 0.001).

CONCLUSIONS: In cases of IDC, re-excision for a close margin or a focally involved margin had no impact on local relapse-free survival. The decision to perform a surgical re-excision for an involved margin should not be systematic but should take multiple risk factors into consideration, such as patient age or margin diffuse involvement.}, } @article {pmid23835924, year = {2013}, author = {Liu, M and Guo, X and Wang, S and Jin, M and Wang, Y and Li, J and Liu, J}, title = {BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1α.}, journal = {European radiology}, volume = {23}, number = {12}, pages = {3221-3227}, pmid = {23835924}, issn = {1432-1084}, mesh = {Adult ; Aged ; Breast Neoplasms/blood/*chemistry/*pathology ; Carcinoma, Ductal/blood/*chemistry/*pathology/secondary ; Cell Hypoxia ; Feasibility Studies ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*analysis ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Grading ; Oxygen/blood ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reproducibility of Results ; Tumor Suppressor Protein p53/analysis ; }, abstract = {OBJECTIVE: To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma.

METHODS: A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1α (HIF-1α). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1α were respectively analysed.

RESULTS: The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 ± 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1α (r = 0.516, P = 0.000).

CONCLUSION: BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas.}, } @article {pmid23833733, year = {2013}, author = {Wang, Y and Ma, Y and Zhu, B}, title = {A huge invasive ductal carcinoma of the left breast.}, journal = {Quantitative imaging in medicine and surgery}, volume = {3}, number = {3}, pages = {182-183}, doi = {10.3978/j.issn.2223-4292.2013.06.07}, pmid = {23833733}, issn = {2223-4292}, abstract = {Breast cancer is the leading malignant tumors among women worldwide, the most common type of breast cancer being invasive ductal carcinoma. We report a case of huge invasive ductal carcinoma of the left breast in an 81-year-old woman.}, } @article {pmid23833125, year = {2013}, author = {McDougall, JA and Malone, KE and Daling, JR and Cushing-Haugen, KL and Porter, PL and Li, CI}, title = {Long-term statin use and risk of ductal and lobular breast cancer among women 55 to 74 years of age.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {22}, number = {9}, pages = {1529-1537}, pmid = {23833125}, issn = {1538-7755}, support = {R01 CA085913/CA/NCI NIH HHS/United States ; T32 CA009168/CA/NCI NIH HHS/United States ; R01 CA 85913/CA/NCI NIH HHS/United States ; T32CA09168/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/chemically induced/*epidemiology/pathology ; Carcinoma, Ductal, Breast/chemically induced/*epidemiology/pathology ; Carcinoma, Lobular/chemically induced/*epidemiology/pathology ; Case-Control Studies ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage/adverse effects ; Middle Aged ; Risk Factors ; Washington/epidemiology ; }, abstract = {BACKGROUND: Mechanistic studies largely support the chemopreventive potential of statins. However, results of epidemiologic studies investigating statin use and breast cancer risk have been inconsistent and lacked the ability to evaluate long-term statin use.

METHODS: We used data from a population-based case-control study of breast cancer conducted in the Seattle-Puget Sound region to investigate the relationship between long-term statin use and breast cancer risk. Nine hundred sixteen invasive ductal carcinoma (IDC) and 1,068 invasive lobular carcinoma (ILC) cases in patients 55 to 74 years of age diagnosed between 2000 and 2008 were compared with 902 control women. All participants were interviewed in-person and data on hypercholesterolemia and all episodes of lipid-lowering medication use were collected through a structured questionnaire. We assessed the relationship between statin use and IDC and ILC risk using polytomous logistic regression.

RESULTS: Current users of statins for 10 years or longer had a 1.83-fold increased risk of IDC [95% confidence interval (CI): 1.14-2.93] and a 1.97-fold increased risk of ILC (95% CI: 1.25-3.12) compared with never users of statins. Among women diagnosed with hypercholesterolemia, current users of statins for 10 years or longer had more than double the risk of both IDC (OR: 2.04, 95% CI: 1.17-3.57) and ILC (OR: 2.43, 95% CI: 1.40-4.21) compared with never users.

CONCLUSION: In this contemporary population-based case-control study, long-term use of statins was associated with increased risks of both IDC and ILC.

IMPACT: Additional studies with similarly high frequencies of statin use for various durations are needed to confirm this novel finding.}, } @article {pmid23831470, year = {2013}, author = {Erez, N and Glanz, S and Raz, Y and Avivi, C and Barshack, I}, title = {Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.}, journal = {Biochemical and biophysical research communications}, volume = {437}, number = {3}, pages = {397-402}, doi = {10.1016/j.bbrc.2013.06.089}, pmid = {23831470}, issn = {1090-2104}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Chemokine CXCL1/biosynthesis ; Cyclooxygenase 2/biosynthesis ; Disease Progression ; Female ; Fibroblasts/metabolism/*pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Inflammation Mediators/*metabolism/physiology ; Interleukin-6/biosynthesis ; NF-kappa B/biosynthesis ; Ovarian Neoplasms/genetics/metabolism/*pathology ; Retrospective Studies ; Signal Transduction/genetics ; Stromal Cells/metabolism/pathology ; }, abstract = {Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.}, } @article {pmid23829889, year = {2013}, author = {Quintyne, KI and Woulfe, B and Coffey, JC and Gupta, RK}, title = {Correlation between Nottingham Prognostic Index and Adjuvant! Online prognostic tools in patients with early-stage breast cancer in Mid-Western Ireland.}, journal = {Clinical breast cancer}, volume = {13}, number = {4}, pages = {233-238}, doi = {10.1016/j.clbc.2013.02.011}, pmid = {23829889}, issn = {1938-0666}, mesh = {Adjuvants, Pharmaceutic/*therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Female ; Humans ; Ireland ; Kaplan-Meier Estimate ; Neoplasm Staging ; Prognosis ; }, abstract = {BACKGROUND: Prognostic tools are widely used in the practice of oncology and have been developed to help stratify patients into specific risk-related grouping. We sought to apply tool such tools used for patients with early-stage breast cancer (EBC) and correlate them to actual outcomes.

METHODS: A retrospective analysis was designed to include EBC cases seen at the Mid-Western Regional Hospital from January 1, 2002, to December 31, 2002. Information was derived from the patients' records, and indices were derived from prognostic tools. Information was analyzed using descriptive statistics and chi-square or Fisher exact test.

RESULTS: A total of 77 patients were found, with a median age of 52.2 years. A median overall survival (OS) of 84 months was observed. The majority presented with moderately differentiated estrogen receptor positive invasive ductal carcinoma and lymph node involvement (60%). Sixty-four percent of patients underwent mastectomy as opposed to breast conservation. Adjuvant cytotoxic chemotherapy uptake was 61%, which was comparable to the proportion of node positive disease. The Nottingham Prognostic Index and Adjuvant! Online (AO) tools were both correlated with actual survival, with the AO showing better correlation.

CONCLUSIONS: This report underscores that these predicting tools were both underestimations consistent with the actual OS and highlights the importance of further work in validating these tools within our own population.}, } @article {pmid23826974, year = {2013}, author = {Pang, JM and Dobrovic, A and Fox, SB}, title = {DNA methylation in ductal carcinoma in situ of the breast.}, journal = {Breast cancer research : BCR}, volume = {15}, number = {3}, pages = {206}, pmid = {23826974}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinogenesis ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; DNA Methylation/*genetics ; *Epigenesis, Genetic ; Female ; Humans ; Promoter Regions, Genetic ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive carcinoma of the breast. Current prognostic markers based on histopathological examination are unable to accurately predict which DCIS cases will progress to invasive carcinoma or recur after surgical excision. Epigenetic changes have been shown to be a significant driver of tumorigenesis, and DNA methylation of specific gene promoters provides predictive and prognostic markers in many types of cancer, including invasive breast cancer. In general, the spectrum of genes that are methylated in DCIS strongly resembles that seen in invasive ductal carcinoma. The identification of specific prognostic markers in DCIS remains elusive and awaits additional work investigating a large panel of methylatable genes by using sensitive and reproducible technologies. This review critically appraises the role of methylation in DCIS and its use as a biomarker.}, } @article {pmid23826951, year = {2013}, author = {Gruber, IV and Rueckert, M and Kagan, KO and Staebler, A and Siegmann, KC and Hartkopf, A and Wallwiener, D and Hahn, M}, title = {Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {328}, pmid = {23826951}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma in Situ/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Carcinoma, Lobular/diagnostic imaging/pathology ; Diagnostic Imaging/*methods ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: Tumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result.

METHODS: Data from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups "ductal carcinoma in situ (DCIS)", invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)", "invasive ductal carcinoma (IDC)", "invasive lobular carcinoma (ILC)" and "other tumours" (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes.

RESULTS: Tumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC.

CONCLUSIONS: The histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible.}, } @article {pmid23826463, year = {2013}, author = {Shinohara, T and Yamada, H and Fujimori, Y and Yamagishi, K}, title = {Malignant pleural effusion in breast cancer 12 years after mastectomy that was successfully treated with endocrine therapy.}, journal = {The American journal of case reports}, volume = {14}, number = {}, pages = {184-187}, pmid = {23826463}, issn = {1941-5923}, abstract = {UNLABELLED: Patient: Female, 94Final Diagnosis: Malignant pleural effusionSymptoms: -Medication: -Clinical Procedure: CytologySpecialty: Oncology.

OBJECTIVE: Unusual clinical course.

BACKGROUND: The most common site of postoperative breast cancer recurrence is bone, followed by local relapse, lung, and liver. The majority of relapses occur within the first 3 years after surgery. Pleural recurrences more than 10 years after surgery are rare.

CASE REPORT: A 94-year-old woman who had undergone modified radical mastectomy for right breast cancer (invasive ductal carcinoma, pT2, pN1, ER+, PgR+) 12 years earlier presented to our hospital with carcinomatous pleuritis and a chief complaint of dyspnea. Endocrine therapy with oral letrozole was started and the pleural effusion had disappeared 3 months later.

CONCLUSIONS: Oral endocrine therapy may be effective for the treatment of late recurrence of hormon receptor-positive breast cancer in elderly women.}, } @article {pmid23826420, year = {2013}, author = {Zhang, J and Wang, Y and Yin, Q and Zhang, W and Zhang, T and Niu, Y}, title = {An associated classification of triple negative breast cancer: the risk of relapse and the response to chemotherapy.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {7}, pages = {1380-1391}, pmid = {23826420}, issn = {1936-2625}, mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal, Breast/chemistry/*classification/*drug therapy/secondary ; Carcinoma, Medullary/chemistry/*classification/*drug therapy/secondary ; Chi-Square Distribution ; China ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/chemistry/*classification/*drug therapy/pathology ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and considered as an aggressive tumor. This study was to evaluate the associated classification and its correlations with prognosis and the response to chemotherapy in Chinese women.

METHODS: Four hundred and twenty-eight cases of invasive TNBC were involved in this study. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6), Ki67 and p53 were analyzed by immunohistochemistry and compared with patient outcome, and its implications and chemotherapy response were evaluated in four subgroups: typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), non-specific invasive ductal carcinoma (IDC) and other types.

RESULTS: The factors of tumor grade, tumor stage, lymph node status, EGFR/CK5/6 status and p53 labeling index were different among the groups. TMC tumors had the lowest rate of relapse (5.8%), while AMC, IDC and other types were associated with an increased risk of relapse (19.1%, 26.7% and 38.2% respectively). Many factors were risk predictors of relapse for TNBC and IDC, while only positive lymph node was for AMC. For MC tumors, adjunctive chemotherapy decreased the risk of relapse in lymph node positive subgroup (36.8% and 66.7%), while not significant in lymph node negative one (8.1% and 10.0%).

CONCLUSION: The classification based on histologic and IHC findings may be a significant improvement in predicting outcome in TNBC. The different chemotherapy response in subgroups may contribute to guiding the treatment of TNBC.}, } @article {pmid23821212, year = {2013}, author = {Kuo, YJ and Weinreb, I and Perez-Ordonez, B}, title = {Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.}, journal = {Head and neck pathology}, volume = {7 Suppl 1}, number = {Suppl 1}, pages = {S59-67}, pmid = {23821212}, issn = {1936-0568}, mesh = {Biomarkers, Tumor/analysis ; Carcinoma in Situ/classification/metabolism/*pathology ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Salivary Ducts/metabolism/*pathology ; Salivary Gland Neoplasms/classification/metabolism/*pathology ; }, abstract = {Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.}, } @article {pmid23820547, year = {2013}, author = {Tan, TJ and Leong, LC and Sim, LS}, title = {Clinics in diagnostic imaging (147). Male breast carcinoma.}, journal = {Singapore medical journal}, volume = {54}, number = {6}, pages = {347-352}, doi = {10.11622/smedj.2013130}, pmid = {23820547}, issn = {2737-5935}, mesh = {Biopsy, Needle ; Breast Neoplasms, Male/*diagnosis/*diagnostic imaging ; Diagnosis, Differential ; Gynecomastia/diagnosis/diagnostic imaging ; Humans ; Male ; Mammography/*methods ; Middle Aged ; Ultrasonography, Doppler ; Ultrasonography, Mammary ; }, abstract = {A 51-year-old man with no significant medical history was referred to our institution for further management of a palpable, painless right breast lump that had been gradually increasing in size for a period of six months. Physical examination revealed a firm right breast lump and bloody right nipple discharge, but no skin involvement or axillary lymphadenopathy was observed. Subsequent mammography and breast ultrasonography demonstrated a discrete, heterogeneous and vascular right breast mass with spiculated and angulated margins. The breast mass was found to be an invasive ductal carcinoma on ultrasonography-guided core needle biopsy. This case illustrates that a combination of detailed clinical history, careful physical examination and radiological assessment using mammography and breast ultrasonography may be used to identify cases suspicious for male breast carcinoma that warrant biopsy.}, } @article {pmid23818344, year = {2013}, author = {Panou, M and Kavantzas, N and Sergentanis, T and Sakellariou, S and Agrogiannis, G and Chatzipantelis, P and Anastasopoulou, E and Soranoglou, V and Zagouri, F and Korkolopoulou, P and Patsouris, E and Bramis, I and Zografos, GC}, title = {Estimation of maspin's subcellular localization in invasive ductal breast cancer via light microscopy and computerized image analysis: a comparative study.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {18}, number = {2}, pages = {342-351}, pmid = {23818344}, issn = {1107-0625}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology/therapy ; Carcinoma, Ductal, Breast/*chemistry/pathology/therapy ; Cell Nucleus/chemistry ; Cytoplasm/chemistry ; Female ; Humans ; *Image Interpretation, Computer-Assisted ; Immunohistochemistry ; Logistic Models ; *Microscopy ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Observer Variation ; Odds Ratio ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; Serpins/*analysis ; }, abstract = {PURPOSE: Contradictory results have been reported concerning the role of maspin and its cellular distribution in breast cancer. The purpose of this study was to examine the subcellular localization (nuclear-cytoplasmic) of maspin in breast cancer and to compare the evaluation of maspin immunostaining via light microscopy (LM) to the estimation via computerized image analysis (CIA) system. We also examined correlations between maspin expression and several clinicopathological parameters.

METHODS: The sample consisted of 48 primary invasive ductal carcinomas (IDC) of the breast. Maspin immunostaining was quantified and graded via LM by two pathologists, separately in the nuclear and cytoplasmic compartments. Total maspin expression was also estimated via CIA system. Univariate non-parametric statistics and stepwise multivariate ordinal logistic regression were performed.

RESULTS: Both maspin components (nuclear and cytoplasmic) were closely associated with each other (p<0.001). Total maspin score was positively and closely associated with nuclear maspin (p<0.001) and cytoplasmic maspin (p<0.001). Total maspin , nuclear maspin and cytoplasmic maspin did not correlate significantly with either age, grade, T, N and M status, stage, micro vessel density (MVD) (CD34), ki-67, p53, estrogen receptor (ER) and HER-2 status, or with any of the 4 groups of the molecular classification. The only factor that showed a borderline inverse correlation with nuclear maspin (p=0.059) was progesterone receptors (PR) positivity.

CONCLUSION: The cytoplasmic and nuclear fractions of maspin seem to be closely interwoven. Evidently, both mutually intertwined counterparts were independently reflected upon the total maspin levels measured by CIA. Future studies should ideally encompass all three approaches (nuclear, cytoplasmic, total) adopted herein.}, } @article {pmid23814724, year = {2013}, author = {Pai, K and Baliga, P and Shrestha, BL}, title = {E-cadherin expression: a diagnostic utility for differentiating breast carcinomas with ductal and lobular morphologies.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {7}, number = {5}, pages = {840-844}, pmid = {23814724}, issn = {2249-782X}, abstract = {OBJECTIVES: The objective of this study was to evaluate the diagnostic utility of the E-Cadherin (EC) expression in differentiating between an infiltrating ductal carcinoma (IDC) and an infiltrating lobular carcinoma (ILC), the two most common forms of invasive breast carcinomas.

METHODS: The authors evaluated the E-Cadherin expression by doing immunohistochemistical studies of all the cases of invasive lobular carcinomas (ILC) which were diagnosed in the pathology laboratory during a 3 year period and they compared the expression of E-Cadherin in an equal number of invasive ductal carcinomas (IDC) of the breast.

RESULTS: A moderate to strong inter-membranous E-Cadherin expression on immunohistochemistry was seen in all the cases of IDC, while only 1 case of ILC showed a moderate E-Cadherin expression. Hence, the E-cadherin expression can be reliably used as a marker to differentiate IDC and ILC. However, an aberrant cytoplasmic expression of E-Cadherin may be seen in some cases of ILC, which should be interpreted with caution.}, } @article {pmid23809739, year = {2013}, author = {Padilha, M and Gonçalves, S and Fardilha, C and Melo, G and Miranda, C and Alves, P}, title = {[Hypofractionation in locally advanced breast cancer: "flash" scheme].}, journal = {Acta medica portuguesa}, volume = {26}, number = {2}, pages = {98-101}, pmid = {23809739}, issn = {1646-0758}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*radiotherapy ; *Dose Fractionation, Radiation ; Female ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {INTRODUCTION: Breast cancer is a major cause of death in our country. The Department of Radiation Oncology of Portuguese Institute of Oncology in Coimbra are using a scheme of hypofraccionation called "Flash" as a treatment option for elderly patients or low performance status, with locally advanced breast cancer, or with stage IIb or IV, as a neoadjuvante or palliative aim.

OBJECTIVES: Evaluation of the therapeutic response, for the group of patients selected, who did the hypofractionated schemed, in a retrospective study.

METHODS: Between January 2006 and December 2008, a total of 83 patients diagnosed with locally advanced breast cancer or with stage IIb or IV, were subjected to breast "Flash". The radiation dose prescribed was 13Gy in 2 fractions in 3 days (in 23 patients - 27.7%) and 26 Gy in 4 fractions in 5 weeks (60 patients - 72.3%), with 4MV photons, in the sick breast. Global survival was evaluated using the Kaplan-Meier method. Statistical analysis was performed by applying the version 17.0 of SPSS and statistical tests were evaluated at a significance level of 5%.

RESULTS: 80 patients (96.4%) who have made breast "Flash" were female, aged between 59 and 93 years and performance status (Karnosfky scale) between 90 and 50%. In 72 patients (86.7%) the histology was invasive ductal carcinoma. Surgery was held in 53% of patients (44) after breast "Flash", the radical modified mastectomy was the most common surgical technique. The diagnosis of bone metastasis was made in 10 patients (12%), while the global survival rate was 68.7% (57 patients). 10 patients (12%) died because disease progression or persistence. In 50.6% (42 patients) there was no evidence of disease progression and 3.6% (3 patients) showed clinical improvement.

CONCLUSIONS: The "Breast Flash" is a safe treatment modality, in terms of secondary effects, and a valid therapeutic option for elderly patients or low performance status, with the diagnosis of locally advanced cancer or stage IIb or IV, as neoadjuvante, adjuvant or palliative aim. There is a little risk of relapse or progression in patients with good conditions, so the global survival rate is greater in these cases. There is a little iatrogenesis associated with this type of treatment; just one patient had grade III radiodermatitis.}, } @article {pmid23807750, year = {2013}, author = {Bravaccini, S and Granato, AM and Medri, L and Foca, F and Falcini, F and Zoli, W and Ricci, M and Lanzanova, G and Masalu, N and Serra, L and Buggi, F and Folli, S and Silvestrini, R and Amadori, D}, title = {Biofunctional characteristics of in situ and invasive breast carcinoma.}, journal = {Cellular oncology (Dordrecht)}, volume = {36}, number = {4}, pages = {303-310}, pmid = {23807750}, issn = {2211-3436}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology/therapy ; Cell Line, Tumor ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local ; Neovascularization, Pathologic/pathology ; Outcome Assessment, Health Care/statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-kit/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {PURPOSE: The increasing use of breast-conserving surgery makes it essential to identify biofunctional profiles responsible for the progression of in situ to invasive carcinomas to facilitate the detection of lesions that are most likely to relapse or progress and, thus, to be able to offer patients tailored treatment options. Our objective was to analyse and compare biofunctional profiles in ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC). We also aimed to identify markers in tumor and normal surrounding tissues that may be predictive of locoregional recurrence in patients with DCIS.

METHODS: Biofunctional parameters including mitotic activity, estrogen receptor, progesterone receptor, microvessel density (MVD), c-kit and p27 expression were evaluated in 829 in situ and invasive carcinomas. The impact of the biomarker profiles of DCIS, IDC and normal surrounding tissues on loco-regional recurrence was analyzed.

RESULTS: A progressive increase in cell proliferation and a concomitant decrease in steroid hormone receptor-positive lesions was observed during the transition from in situ to invasive carcinomas, as also within each subgroup as grade increased. Conversely, p27 expression and MVD dramatically decreased during the transition from in situ to invasive carcinomas. Finally, we found that a low c-kit expression was indicative of IDC relapse.

CONCLUSIONS: Cell proliferation, hormonal and differentiation characteristics differed in DCIS with respect to IDC, and the main variation in the transition between the two histologic lesions was the decrease in p27 expression and MVD.}, } @article {pmid23807171, year = {2013}, author = {Bamias, A and Tzannis, K and Beuselinck, B and Oudard, S and Escudier, B and Diosynopoulos, D and Papazisis, K and Lang, H and Wolter, P and de Guillebon, E and Stravodimos, K and Chrisofos, M and Fountzilas, G and Elaidi, RT and Dimopoulos, MA and Bamia, C}, title = {Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration.}, journal = {British journal of cancer}, volume = {109}, number = {2}, pages = {332-341}, pmid = {23807171}, issn = {1532-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Renal Cell/*drug therapy/*mortality/secondary ; Cohort Studies ; European Union ; Female ; Humans ; Indoles/*therapeutic use ; Kidney Neoplasms/*drug therapy/mortality/pathology ; Male ; Middle Aged ; *Models, Statistical ; Neoplasm Metastasis ; Predictive Value of Tests ; Prognosis ; Pyrroles/*therapeutic use ; Sunitinib ; Survival Analysis ; }, abstract = {BACKGROUND: Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.

METHODS: The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.

RESULTS: Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.

CONCLUSION: Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models.}, } @article {pmid23792752, year = {2013}, author = {Doron, G and Szepsenwol, O and Karp, E and Gal, N}, title = {Obsessing about intimate-relationships: testing the double relationship-vulnerability hypothesis.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {44}, number = {4}, pages = {433-440}, doi = {10.1016/j.jbtep.2013.05.003}, pmid = {23792752}, issn = {1873-7943}, mesh = {Adolescent ; Adult ; Anxiety/psychology ; Compulsive Personality Disorder/psychology ; Culture ; Depression/psychology ; Feedback, Psychological ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Object Attachment ; Obsessive Behavior/*psychology ; Regression Analysis ; Self Concept ; Surveys and Questionnaires ; Word Association Tests ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Obsessive preoccupation and doubts centering on one's intimate relationship may have a negative impact on the romantic dyad and lead to significant distress. In this research we investigated whether the co-occurrence of attachment anxiety and overreliance on intimate relationships for self-worth-what we call double relationship-vulnerability-is linked with relationship-centered obsessions and obsessive-compulsive tendencies.

METHODS: Study 1 employed a correlational design to examine the link between double relationship-vulnerability and relationship-centered obsessions. Study 2 employed an experimental design to assess response to subtle threats to the relationship self-domain among individuals with double relationship-vulnerability.

RESULTS: Study 1 supported the link between double relationship-vulnerability and relationship-centered obsessions. Study 2 showed that when confronted with subtle threats to the relationship self-domain, individuals with double relationship-vulnerability are more likely to experience distress and engage in mitigating behavior in response to relationship doubts and fears.

LIMITATIONS: Our studies were conducted with non-clinical samples.

CONCLUSIONS: These findings suggest that double relationship-vulnerability may make individuals more susceptible to the development and maintenance of relationship-centered obsessions and compulsions.}, } @article {pmid23792484, year = {2013}, author = {Nakamura, T and Masuda, K and Harada, S and Akioka, K and Sako, H}, title = {Pancreatic cancer: Slow progression in the early stages.}, journal = {International journal of surgery case reports}, volume = {4}, number = {8}, pages = {693-696}, pmid = {23792484}, issn = {2210-2612}, abstract = {INTRODUCTION: The rates of pancreatic cancer development in the early stages of growth remain unclear; but it is generally believed that they demonstrate a rapid degree of progression. There is evidence to suggest that pancreatic cancers measuring less than 1cm demonstrate better survival rates, hence it is clear that detecting pancreatic cancers less than 1cm in size is of paramount importance. However, to date, there has been no scientifically adequate research to show the growth rate of small pancreatic cancers less than 1cm in the early stages.

PRESENTATION OF CASE: We present the case of a 65-year-old woman whose small pancreatic cancer possibly demonstrated a slow progressive rate as it grew to an invasive carcinoma measuring 1cm diameter from over the 29 months.

DISCUSSION: It is reasonable to assume that the progression of some pancreatic cancers until 1cm size, can take up to 29 months. During this silent period, it is crucial to detect such a small pancreatic cancer by means of the initial US and subsequent EUS and ERCP. It is clear, therefore, that clinicians have to be aware of the growth rate of small pancreatic cancers and in particular high risk patients should be encouraged to monitor size of the main pancreatic duct by means of US on regular basis.

CONCLUSION: This could give better outcomes for pancreatic cancer patients. Hopefully, by detecting these lethal, pancreatic cancers in their early stages, it will give us an extension of time to perform effective therapies.}, } @article {pmid23792450, year = {2014}, author = {Novitskaya, V and Romanska, H and Kordek, R and Potemski, P and Kusińska, R and Parsons, M and Odintsova, E and Berditchevski, F}, title = {Integrin α3β1-CD151 complex regulates dimerization of ErbB2 via RhoA.}, journal = {Oncogene}, volume = {33}, number = {21}, pages = {2779-2789}, doi = {10.1038/onc.2013.231}, pmid = {23792450}, issn = {1476-5594}, mesh = {Antibodies, Monoclonal, Humanized/pharmacology ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/*metabolism/mortality ; Cell Line, Tumor ; Cell Polarity ; Female ; Humans ; Integrin alpha3beta1/*metabolism ; Phosphorylation ; Prognosis ; Proportional Hazards Models ; Protein Multimerization ; Protein Processing, Post-Translational ; Receptor, ErbB-2/*metabolism ; Signal Transduction ; Tetraspanin 24/*metabolism ; Trastuzumab ; rhoA GTP-Binding Protein ; }, abstract = {Integrin α3β1 regulates adhesive interactions of cells with laminins and have a critical role in adhesion-dependent cellular responses. Here, we examined the role of α3β1-integrin in ErbB2-dependent proliferation of breast cancer cells in three-dimensional laminin-rich extracellular matrix (3D lr-ECM). Depletion of α3β1 in ErbB2-overexpressing breast cancer cells suppressed growth and restore cell polarity in 3D lr-ECM. The phenotype of α3β1-depleted cells was reproduced upon depletion of tetraspanin CD151 and mirrored that of the cells treated with Herceptin, an established ErbB2 antagonist. Breast cancer cells expressing the α3β1-CD151 complex have higher steady-state phosphorylation of ErbB2 and show enhanced dimerization of the protein when compared with α3β1-/CD151-depleted cells. Furthermore, Herceptin-dependent dephosphorylation of ErbB2 was only observed in α3β1-CD151-expressing cells. Importantly, the inhibitory activity of Herceptin was more pronounced when cells expressed both α3β1 and CD151. We also found that the level of active RhoA was increased in α3β1- and CD151-depleted cells and that Rho controls dimerization of ErbB2. Expression of α3β1 alone did not have significant prognostic value in patients with invasive ductal carcinoma of the breast. However, expression of α3β1 in combination with CD151 represented a more stringent indicator of poor survival than CD151 alone. Taken together, these results demonstrate that the α3β1-CD151 complex has a critical regulatory role in ErbB2-dependent signalling and thereby may be involved in breast cancer progression.}, } @article {pmid23790170, year = {2013}, author = {Pula, B and Wojnar, A and Witkiewicz, W and Dziegiel, P and Podhorska-Okolow, M}, title = {Podoplanin expression in cancer-associated fibroblasts correlates with VEGF-C expression in cancer cells of invasive ductal breast carcinoma.}, journal = {Neoplasma}, volume = {60}, number = {5}, pages = {516-524}, doi = {10.4149/neo_2013_067}, pmid = {23790170}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Fibroblasts/*metabolism ; Humans ; Immunohistochemistry ; Lymphangiogenesis/physiology ; Membrane Glycoproteins/*biosynthesis ; Middle Aged ; Neovascularization, Pathologic/metabolism/pathology ; Vascular Endothelial Growth Factor C/*biosynthesis ; }, abstract = {Podoplanin (D2-40) was shown to be expressed in cancer-associated fibroblasts (CAFs) of various malignancies. The study aimed at examining its impact on angiogenesis and lymphangiogenesis markers in invasive ductal carcinoma of the breast (IDC). The studies were performed on 104 archival cases of IDC using immunohistochemical technique. Podoplanin expression in CAFs correlated positively with cancer cell VEGF-C expression (r=0.19, p=0.0495) and intratumoral microvessel count (MVC) of CD31 positive vessels (r=0.30, p=0.0018), whereas negative correlations were observed with peritumoral MVC of D2-40 and Lyve-1 positive lymphatic vessels (r=-0.26, p=0.008 and r=-0.27, p=0.0058, respectively). Podoplanin expression in CAFs did not correlate with VEGF-A and VEGF-D expression in cancer cells, nor exerted any prognostic significance. Podoplanin expression in CAFs may have impact on angio- and lymphangiogenesis processes in IDC.}, } @article {pmid23790130, year = {2014}, author = {Santangelo, G and Vitale, C and Trojano, L and Angrisano, MG and Picillo, M and Errico, D and Agosti, V and Grossi, D and Barone, P}, title = {Subthreshold depression and subjective cognitive complaints in Parkinson's disease.}, journal = {European journal of neurology}, volume = {21}, number = {3}, pages = {541-544}, doi = {10.1111/ene.12219}, pmid = {23790130}, issn = {1468-1331}, mesh = {Aged ; Cognition Disorders/*etiology ; Depression/*etiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Parkinson Disease/*complications ; Psychiatric Status Rating Scales ; }, abstract = {BACKGROUND AND PURPOSE: Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients.

METHODS: Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions.

RESULTS: On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients.

CONCLUSIONS: SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being.}, } @article {pmid23787124, year = {2013}, author = {Lai, HW and Tseng, LM and Chang, TW and Kuo, YL and Hsieh, CM and Chen, ST and Kuo, SJ and Su, CC and Chen, DR}, title = {The prognostic significance of metaplastic carcinoma of the breast (MCB)--a case controlled comparison study with infiltrating ductal carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {968-973}, doi = {10.1016/j.breast.2013.05.010}, pmid = {23787124}, issn = {1532-3080}, mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms/chemistry/*pathology ; Carcinoma/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Lobular/chemistry/pathology ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; Triple Negative Breast Neoplasms/pathology ; Tumor Burden ; }, abstract = {PURPOSE: Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with an incidence of less than 0.1%-0.5%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancers (like infiltrating ductal carcinoma [IDC], and infiltrating lobular carcinoma [ILC]) are not clear, and controversial among different reports.

METHODS: We performed a collective comparison study of multi-institutional cases to evaluate the clinical characteristics and prognostic status of MCB to compare with IDC and ILC. A case control analysis was performed to minimize the bias from clinicopathologic factors between IDC and MCB. Disease free survival (DFS) and overall survival (OS) between groups were compared.

RESULTS: Forty-five MCB patients were enrolled from the 4 medical centers and compared with 1777 IDC and 53 ILC patients from the CCH cancer registry database comprise the current study. Compared with IDC, MCB was associated with older age, larger tumor size, a lesser lymph node positive rate, a higher likelihood of distant metastasis, higher tumor grade, lower ER-positive tumor, and higher triple negative breast cancer subtype (TNBC). MCB was associated with worse OS (p = 0.031) than IDC, but no difference in DFS (p = 0.071); however, MCB was not statistically different from ILC in both DFS and OS (p = 0.289 and 0.132, respectively). Compared with the case-controlled IDC group, MCB patients had poorer OS (p = 0.040), but no difference in DFS (p = 0.439).

CONCLUSION: MCB is associated with poorer OS than IDC, and this was related to tumor behavior rather than clinicopathologic factors.}, } @article {pmid23782331, year = {2013}, author = {Tazaki, E and Shishido-Hara, Y and Mizutani, N and Nomura, S and Isaka, H and Ito, H and Imi, K and Imoto, S and Kamma, H}, title = {Histopathologcial and clonal study of combined lobular and ductal carcinoma of the breast.}, journal = {Pathology international}, volume = {63}, number = {6}, pages = {297-304}, pmid = {23782331}, issn = {1440-1827}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/genetics/*pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; DNA Methylation ; Female ; Humans ; Immunohistochemistry ; Japan ; Middle Aged ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Receptors, Androgen/genetics ; Retrospective Studies ; Risk Factors ; beta Catenin/metabolism ; }, abstract = {Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.}, } @article {pmid23769438, year = {2013}, author = {Li, MP and Ren, LF and Cai, HG and Yang, HY and Lu, B and Zhang, P and Bao, L}, title = {[Significance of carbonic anhydrase IX protein expression in molecular subtyping of breast cancers].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {42}, number = {3}, pages = {182-185}, doi = {10.3760/cma.j.issn.0529-5807.2013.03.009}, pmid = {23769438}, issn = {0529-5807}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/classification/*metabolism/pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases/*metabolism ; Carcinoma, Ductal, Breast/classification/*metabolism/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Burden ; }, abstract = {OBJECTIVE: To study the expression of carbonic anhydrase (CA) IX and its significance in molecular subtyping of breast carcinomas. METHODL MaxVision immunohistochemical staining was used to examine the expression of ER, PR, HER2, CK5/6, EGFR, and CA IX in 117 cases of breast invasive ductal carcinomas.

RESULTS: The patients' age ranged from 25 to 71 years (mean 49.6 years). All the 117 cases were subclassified into five subtypes, with 66 (56.4%) luminal A, 6(5.1%) luminal B, 10 (8.6%) HER2 positive, 20 (17.1%) basal-like, and 15 (12.8%) unclassified tumors. The expression of CA IX in luminal A and basal-like breast cancers was 13.6% (9/66) and 8/20, respectively, with a significant difference (P < 0.05). Among the luminal A cancers, the expression of CA IX in tumors > 2 cm (7/27, 25.9%) was significantly (P < 0.05) higher than that of tumors ≤ 2 cm (2/39, 5.1%). The expression of CA IX in grade 3 invasive ductal carcinoma (18/50, 36.0%) was significantly higher than that in grade 1 (2/21, 9.5%) and 2 (7/46, 15.2%) tumors (both P = 0.006). In CA IX-negative of invasive ductal carcinoma, the expression of ER and PR was 61.1% (55/90) and 55.6% (50/90), respectively; whereas in CA IX-positive cancers, the expression of ER and PR was 37.0% (10/27) and 29.6% (8/27), respectively. The expression of hormone receptors in CA IX-negative tumors was significantly higher than that in CA IX-positive tumors (for both ER and PR, P < 0.05).

CONCLUSIONS: The expression of CA IX correlates not only with molecular subtypes of breast cancer, but also with the grading, hormone receptors and diameter of mammary invasive ductal carcinoma. CA IX is a relative independent marker of poor prognosis in breast cancer.}, } @article {pmid23768133, year = {2013}, author = {Tseng, HS and Lin, C and Chan, SE and Chien, SY and Kuo, SJ and Chen, ST and Chang, TW and Chen, DR}, title = {Pure mucinous carcinoma of the breast: clinicopathologic characteristics and long-term outcome among Taiwanese women.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {139}, pmid = {23768133}, issn = {1477-7819}, mesh = {Adenocarcinoma, Mucinous/*mortality/pathology/therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Taiwan ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: Pure mucinous carcinoma (MC) is found in about 3.5% of all newly diagnosed breast cancer patients in Taiwan. MC is a relatively rare malignancy of breast cancer, and its nature, behaviors, treatment pattern and long-term follow-up are not well understood. The study aimed to investigate the incidence rate, treatment patterns, and prognostic factors of MC of the breast and the clinical long-term outcomes compared with infiltrating ductal carcinoma not otherwise specified (IDC) in the middle and south Taiwanese women.

METHODS: Data from 93 patients with breast MC were retrospectively reviewed and the clinicopathologic characteristics and survival status were compared with those of 2,674 patients with IDC.

RESULTS: The expression of hormonal receptor was higher in MC than those in IDC (P <0.001). MC also demonstrated lower Her2/neu gene over-expression (P = 0.023), less axillary lymph node involvement (P <0.0001), lymphovascular invasion (P <0.0001) and higher 10-year overall survival rate (P = 0.042), when compared with those of IDC.

CONCLUSION: Our data confirm the less aggressive behavior of MC compared to IDC. MC showed favorable clinicopathologic characteristics in tumor grade, hormone receptor status and lymph node involvement in the middle and south Taiwanese women.}, } @article {pmid23767668, year = {2013}, author = {Zhong, Y and Lin, Y and Shen, S and Zhou, Y and Mao, F and Guan, J and Sun, Q}, title = {Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse.}, journal = {Cancer cell international}, volume = {13}, number = {1}, pages = {60}, pmid = {23767668}, issn = {1475-2867}, abstract = {BACKGROUND: The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear.

METHODS: 147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated.

RESULTS: ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman's rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2-△△CT value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001).

CONCLUSIONS: The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.}, } @article {pmid23765060, year = {2013}, author = {Jardim, BV and Moschetta, MG and Leonel, C and Gelaleti, GB and Regiani, VR and Ferreira, LC and Lopes, JR and Zuccari, DA}, title = {Glutathione and glutathione peroxidase expression in breast cancer: an immunohistochemical and molecular study.}, journal = {Oncology reports}, volume = {30}, number = {3}, pages = {1119-1128}, doi = {10.3892/or.2013.2540}, pmid = {23765060}, issn = {1791-2431}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis/drug effects ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/pathology ; Cell Proliferation/drug effects ; Chemotherapy, Adjuvant ; Doxorubicin/pharmacology ; Female ; Follow-Up Studies ; Glutathione/*metabolism ; Glutathione Peroxidase/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Tumor Cells, Cultured ; Glutathione Peroxidase GPX1 ; }, abstract = {The use of prognostic markers for breast cancer allows therapeutic strategies to be defined more efficiently. The expression of glutathione (GSH) and glutathione peroxidase (GPX) in tumor cells has been evaluated as a predictor of prognosis and response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results showed that high GSH expression was associated with tumors negative for the estrogen receptor (ER) (P<0.05), and GPX expression was associated with tumors negative for the progesterone receptor (PR) and patient mortality. Focusing on the 37 patients who received adjuvant chemotherapy/radiotherapy (Group I), high expression of GPX was associated with a high rate of patient mortality (P<0.05). The 19 patients who received only adjuvant chemotherapy (Group II) showed high expression of GSH in relation to metastasis (P<0.05). In addition, high levels of GPX expression were significantly associated with a shorter overall survival (P<0.05). To confirm this, the expression of precursor genes of GSH [glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS)] and the GPX gene was analyzed using quantitative PCR in cultured neoplastic mammary cells treated with doxorubicin. Doxorubicin treatment was able to eliminate tumor cells without alterations in the gene expression of GSS, but led to underexpression of the GCLC and GPX genes. Our results suggest that high levels of GPX may be related to the development of resistance to chemotherapy in these tumors, response to treatment and the clinical course of the breast cancer patients.}, } @article {pmid23763700, year = {2013}, author = {Vingiani, A and Maisonneuve, P and Dell'orto, P and Farante, G and Rotmensz, N and Lissidini, G and Del Castillo, A and Renne, G and Luini, A and Colleoni, M and Viale, G and Pruneri, G}, title = {The clinical relevance of micropapillary carcinoma of the breast: a case-control study.}, journal = {Histopathology}, volume = {63}, number = {2}, pages = {217-224}, doi = {10.1111/his.12147}, pmid = {23763700}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology/secondary ; Carcinoma, Papillary/metabolism/*pathology/secondary ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {AIMS: To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumour.

METHODS AND RESULTS: We interrogated the clinical records of a series of 49 pure micropapillary carcinoma patients and 13 487 invasive ductal carcinoma patients, diagnosed and treated consecutively in our institution over a 9-year time-frame. Compared with invasive ductal carcinoma, patients with micropapillary carcinoma more frequently had moderately differentiated tumours (P = 0.02) with extensive peritumoral vascular invasion (P < 0.0001), associated with a significantly higher rate of axillary lymph node involvement (P < 0.0001). Survival data obtained by comparing 49 micropapillary carcinoma patients with a set of 98 invasive ductal carcinoma patients matched for age, tumour size and grade, peritumoral vascular invasion, immunohistochemically defined molecular subtype, number of positive lymph nodes and year of surgery showed that the micropapillary histotype did not add any independent information to the risk of locoregional (P = 0.48) or distant (P = 0.79) relapse, or overall survival (P = 0.60).

CONCLUSIONS: Our data reinforce the notion that micropapillary carcinoma usually arises as a locally advanced disease, and provide evidence that micropapillary histology does not add any additional information on clinical outcome independent of clinicopathological characteristics such as lymph node status and immunohistochemically defined molecular subtype.}, } @article {pmid23761829, year = {2013}, author = {Rong, G and Kang, H}, title = {Local recurrence involving the sternum and ribs following mastectomy and titanium mesh implants for chest wall reconstruction: A case report.}, journal = {Oncology letters}, volume = {5}, number = {5}, pages = {1649-1652}, pmid = {23761829}, issn = {1792-1074}, abstract = {Approximately 30% of breast carcinoma patients experience local recurrence, which is commonly considered the first sign of treatment failure. Local recurrence involving the deep chest wall may result in thoracic defects and influence normal cardiopulmonary function. Many studies have reported various techniques using different materials for chest wall reconstruction, and titanium mesh has recently received attention as a novel bone substitute. In the present case report, a 46-year-old female who had not yet entered menopause presented for routine follow-up. Her past history was significant for having had a left modified radical mastectomy followed by chemotherapy and tamoxifen treatment for an invasive ductal breast carcinoma. Examination results revealed an invasive ductal carcinoma invading the chest wall. The patient underwent surgical excision and received a titanium mesh implant for chest wall reconstruction. The patient chose to undergo local radiation therapy and endocrine treatment following surgery. Local recurrence of breast cancer involving the deep chest wall is relatively rare. According to the guidelines, surgical excision followed by radiotherapy is the standard treatment and chemotherapy is not recommended. In our case, a titanium mesh was successfully applied for chest wall reconstruction.}, } @article {pmid23761327, year = {2013}, author = {Wong, JL and Berk, E and Edwards, RP and Kalinski, P}, title = {IL-18-primed helper NK cells collaborate with dendritic cells to promote recruitment of effector CD8+ T cells to the tumor microenvironment.}, journal = {Cancer research}, volume = {73}, number = {15}, pages = {4653-4662}, pmid = {23761327}, issn = {1538-7445}, support = {P01 CA101944/CA/NCI NIH HHS/United States ; P50 CA121973/CA/NCI NIH HHS/United States ; P01CA101944/CA/NCI NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; TL1 RR024155/RR/NCRR NIH HHS/United States ; T32 CA082084/CA/NCI NIH HHS/United States ; F30 CA165410/CA/NCI NIH HHS/United States ; P01 CA132714/CA/NCI NIH HHS/United States ; }, mesh = {CD8-Positive T-Lymphocytes/*immunology/metabolism ; Cell Communication/immunology ; Cell Separation ; Chemotaxis, Leukocyte/*immunology ; Coculture Techniques ; Cytokines/biosynthesis/immunology ; Dendritic Cells/*immunology/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Interleukin-18/immunology/metabolism ; Killer Cells, Natural/*immunology/metabolism ; Lymphocyte Activation/immunology ; Lymphocytes, Tumor-Infiltrating/cytology/immunology/metabolism ; Ovarian Neoplasms ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; *Tumor Microenvironment/immunology ; }, abstract = {Chemokine-driven interactions of immune cells are essential for effective antitumor immunity. Human natural killer (NK) cells can be primed by the interleukin (IL)-1-related proinflammatory cytokine IL-18 for unique helper activity, which promotes dendritic cell (DC) activation and DC-mediated induction of type-1 immune responses against cancer. Here, we show that such IL-18-primed "helper" NK cells produce high levels of the immature DC (iDC)-attracting chemokines CCL3 and CCL4 upon exposure to tumor cells or the additional inflammatory signals IFN-α, IL-15, IL-12, or IL-2. These "helper" NK cells potently attract iDCs in a CCR5-dependent mechanism and induce high DC production of CXCR3 and CCR5 ligands (CXCL9, CXCL10, and CCL5), facilitating the subsequent recruitment of type-1 effector CD8(+) T (Teff) cells. Using cells isolated from the malignant ascites of patients with advanced ovarian cancer, we show that "helper" NK cell-inducing factors can be used to enhance local production of Teff cell-recruiting chemokines. Our findings reveal the unique chemokine expression profile of "helper" NK cells and highlight the potential for using two-signal-activated NK cells to promote homing of type-1 immune effectors to the human tumor environment.}, } @article {pmid23760281, year = {2013}, author = {Buchanan, JJ}, title = {Flexibility in the control of rapid aiming actions.}, journal = {Experimental brain research}, volume = {229}, number = {1}, pages = {47-60}, pmid = {23760281}, issn = {1432-1106}, mesh = {Adaptation, Physiological/*physiology ; Adult ; Female ; Humans ; Male ; Movement/*physiology ; Photic Stimulation/*methods ; Psychomotor Performance/*physiology ; Reaction Time/*physiology ; Young Adult ; }, abstract = {Across three different task conditions, the adaptability of reciprocal aiming movements was investigated. Task difficulty was manipulated by changing ID, with 9 IDs between 2.5 and 6.5 tested. Reciprocal aiming movements were performed with ID scaled (predictable) in a trial in a decreasing (high 6.5-low 2.5) or increasing manner (low 2.5-high 6.5) or with ID constant in a trial and changed randomly across trials. Movement time scaled linearly with ID in both the scaling ID and control ID presentations. A critical ID boundary (IDC) was identified, and the adaptation of aiming movements was a function of this critical boundary. For IDs < IDC, the results are interpreted as representing a predominance for pre-planned control based on a dwell time measure and a symmetry ratio measure (time spent accelerating-decelerating the limb). Within this ID range, movement harmonicity was changed to a greater extent when ID was scaled in a predictable direction as compared to being presented in a random manner. For IDs > IDC, the findings suggest a predominance for feedback control based on the dwell time and symmetry ratio measure. Within this ID range, the absolute time spent decelerating was increased, possibly to insure accuracy and minimize MT, with the predictable changes associated with an increase in ID needing less time devoted to feedback processing compared to the other ID presentations. The results are consistent with the theoretical position that aiming motions may be controlled by a limit cycle mechanism with ID < IDC, while aiming motions may be controlled by a fixed-point mechanism with ID > IDC. The results suggest that the ability of the motor system to adapt to both scaled and random changes in ID revolves around a modulation of pre-planned and feedback-based control processes.}, } @article {pmid23758085, year = {2013}, author = {Hasebe, T and Iwasaki, M and Hojo, T and Shibata, T and Kinoshita, T and Tsuda, H}, title = {Histological factors for accurately predicting first locoregional recurrence of invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {104}, number = {9}, pages = {1252-1261}, pmid = {23758085}, issn = {1349-7006}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/*pathology ; Predictive Value of Tests ; Proportional Hazards Models ; Young Adult ; }, abstract = {The accurate assessment of the risk of first locoregional recurrence is very important for improving the survival of patients with invasive ductal carcinoma of the breast. The present study investigated which histological factors (both well-known histological factors and factors that we have proposed) were the most capable of accurately predicting first locoregional recurrence among 1042 patients with invasive ductal carcinoma and various tumor statuses (overall, nodal status, Union Internationale Contre le Cancer pathological TNM stage, adjuvant therapy status, and adjuvant radiotherapy status) using multivariate analyses by the Cox proportional hazard regression model. The present study clearly demonstrated that the best factor for accurately predicting locoregional recurrence was grade 3 lymph vessel tumor embolus (>4 mitotic figures and >6 apoptotic figures in tumor embolus), followed by type 2 invasive ductal carcinoma (negative for fibrotic foci but positive for atypical tumor-stromal fibroblast), grade 2 lymph vessel tumor embolus (1-4 mitotic figures and >0 apoptotic figures in tumor embolus; >0 mitotic figures and 1-6 apoptotic figures in tumor embolus), primary invasive tumor cell-related factors (>19 mitotic figures, presence of tumor necrosis, presence of skin invasion) and >5 mitotic figures in metastatic carcinomas to the lymph node. Our proposed factors were superior to well-known histological factors of primary invasive tumors or clinicopathological factors for the accurate prediction of first locoregional recurrence in patients with invasive ductal carcinoma of the breast.}, } @article {pmid23756727, year = {2013}, author = {Yust-Katz, S and Garciarena, P and Liu, D and Yuan, Y and Ibrahim, N and Yerushalmi, R and Penas-Prado, M and Groves, MD}, title = {Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis.}, journal = {Journal of neuro-oncology}, volume = {114}, number = {2}, pages = {229-235}, pmid = {23756727}, issn = {1573-7373}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Meningeal Carcinomatosis/diagnosis/metabolism/*secondary/therapy ; Middle Aged ; Multivariate Analysis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Time Factors ; }, abstract = {Leptomeningeal disease (LMD) occurs in 5 % of breast cancer patients. The aim of this study was to identify risk factors related to survival and time to development of LMD in breast cancer patients. A retrospective analysis of breast cancer patients with LMD, evaluated in MDACC between 1995 and 2011. 103 patients with diagnosis of breast cancer and LMD were identified (one male). The median age at LMD diagnosis was 49.2 years. 78.2 % had invasive ductal carcinoma. Hormone receptors (HRs) were positive in 55.3 % of patients, 47.4 % were human epidermal growth factor receptor 2-positive and 22.8 % were triple negative. 52 % of the patients were treated with WBRT, 19 % with spinal radiation, 36 % with systemic chemotherapy and 55 % with intrathecal chemotherapy. Estimated median overall survival from time of breast cancer diagnosis was 3.66 years. Median survival from time of LMD diagnosis was 4.2 months. Time from breast cancer diagnosis to LMD was 2.48 years. In multivariate analysis, HR status and stage at diagnosis were significantly associated with time to LMD diagnosis (p < 0.05). In triple negative patients, time to LMD was shorter. In patients who were HR positive, time to LMD was longer. Survival from LMD diagnosis was significantly associated with both treatment, as well as positive HR status (multivariate analysis p < 0.05). In conclusion LMD has dismal prognosis in breast cancer patients. HR status contributes to time to LMD diagnosis and survival from LMD diagnosis. The impact of treatment aimed at LMD cannot be ascertained in our retrospective study due to the inherent bias associated with the decision to treat.}, } @article {pmid23756383, year = {2013}, author = {Ohara, M and Shigematsu, H and Tsutani, Y and Emi, A and Masumoto, N and Ozaki, S and Kadoya, T and Okada, M}, title = {Role of FDG-PET/CT in evaluating surgical outcomes of operable breast cancer--usefulness for malignant grade of triple-negative breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {958-963}, doi = {10.1016/j.breast.2013.05.003}, pmid = {23756383}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/pharmacokinetics ; Humans ; Middle Aged ; Multimodal Imaging ; Neoplasm Grading ; *Positron-Emission Tomography ; ROC Curve ; Radiopharmaceuticals/pharmacokinetics ; Triple Negative Breast Neoplasms/*diagnosis/surgery ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the significance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers.

METHODS: Of 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined.

RESULTS: Receiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUVmax) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUVmax ≤ 3.8 and 91.6% for patients with a tumor of SUVmax > 3.8 (p < 0.001). High value of SUVmax was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUVmax (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUVmax ≤ 8.6 and 42.9% for patients with a tumor of SUVmax > 8.6 (p = 0.002), and high SUVmax was the only significant independent prognostic factor (p = 0.047).

CONCLUSION: FDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.}, } @article {pmid23754601, year = {2013}, author = {Pécuchet, N and Popova, T and Manié, E and Lucchesi, C and Battistella, A and Vincent-Salomon, A and Caux-Moncoutier, V and Bollet, M and Sigal-Zafrani, B and Sastre-Garau, X and Stoppa-Lyonnet, D and Stern, MH}, title = {Loss of heterozygosity at 13q13 and 14q32 predicts BRCA2 inactivation in luminal breast carcinomas.}, journal = {International journal of cancer}, volume = {133}, number = {12}, pages = {2834-2842}, doi = {10.1002/ijc.28315}, pmid = {23754601}, issn = {1097-0215}, mesh = {Breast Neoplasms/*genetics/pathology ; Chromosome Aberrations ; *Chromosomes, Human, Pair 13 ; *Chromosomes, Human, Pair 14 ; Female ; *Genes, BRCA2 ; Humans ; *Loss of Heterozygosity ; Middle Aged ; Mutation ; Ploidies ; Polymorphism, Single Nucleotide ; }, abstract = {BRCA2 is the major high-penetrance predisposition gene for luminal (estrogen receptor [ER] positive) breast cancers. However, many BRCA2 mutant carriers lack family history of breast/ovarian cancers and do not benefit from genetic testing. Specific genomic features associated with BRCA2 inactivation in tumors could help identify patients for whom a genetic test for BRCA2 may be proposed. A series of ER-positive invasive ductal carcinomas (IDCs) including 30 carriers of BRCA2 mutations and 215 control cases was studied by single-nucleotide polymorphism (SNP) arrays. Cases and controls were stratified by grade and HER2 status. Independently, 7 BRCA2 and 51 control cases were used for validation. Absolute copy number and Loss of heterozygosity (LOH) profiles were obtained from SNP arrays by the genome alteration print (GAP) method. BRCA2 tumors were observed to display a discriminatively greater number of chromosomal breaks calculated after filtering out and smoothing <3 Mb variations. This argues for a BRCA2-associated genomic instability responsible for long-segment aberrations. Co-occurrence of two genomic features-LOH of 13q13 and 14q32-was found to predict BRCA2 status with 90% of sensitivity and 87% of specificity in discovery series of high-grade HER2-negative IDCs and 100% of sensitivity and 88% of specificity in an independent series of 58 IDCs. Estimated positive predictive value was 17.2% (confidence interval: 6.7-33.5) in the whole series. In conclusion, the simplified BRCA2 classifier based on the co-occurrence of LOH at 13q13 and 14q32 could provide an indication to test for BRCA2 mutation in patients with ER-positive IDC.}, } @article {pmid23752191, year = {2014}, author = {Li, Q and Yao, Y and Eades, G and Liu, Z and Zhang, Y and Zhou, Q}, title = {Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer.}, journal = {Oncogene}, volume = {33}, number = {20}, pages = {2589-2600}, pmid = {23752191}, issn = {1476-5594}, support = {R01 CA157779/CA/NCI NIH HHS/United States ; P30 CA134274/CA/NCI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase 1 Family ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Line, Tumor ; *Down-Regulation ; Epigenesis, Genetic ; Female ; Humans ; Isoenzymes/metabolism ; MicroRNAs/*metabolism ; Neoplastic Stem Cells/*pathology ; Retinal Dehydrogenase/metabolism ; SOX9 Transcription Factor/metabolism ; }, abstract = {The major goal of breast cancer prevention is to reduce the incidence of ductal carcinoma in situ (DCIS), an early stage of breast cancer. However, the biology behind DCIS formation is not well understood. It is suspected that cancer stem cells (CSCs) are already programmed in pre-malignant DCIS lesions and that these tumor-initiating cells may determine the phenotype of DCIS. MicroRNA (miRNA) profiling of paired DCIS tumors revealed that loss of miR-140 is a hallmark of DCIS lesions. Previously, we have found that miR-140 regulates CSCs in luminal subtype invasive ductal carcinoma. Here, we find that miR-140 has a critical role in regulating stem cell signaling in normal breast epithelium and in DCIS. miRNA profiling of normal mammary stem cells and cancer stem-like cells from DCIS tumors revealed that miR-140 is significantly downregulated in cancer stem-like cells compared with normal stem cells, linking miR-140 and dysregulated stem cell circuitry. Furthermore, we found that SOX9 and ALDH1, the most significantly activated stem-cell factors in DCIS stem-like cells, are direct targets of miR-140. Currently, targeted therapies (tamoxifen) are only able to reduce DCIS risk in patients with estrogen receptor α (ERα)-positive disease. We examined a model of ERα-negative/basal-like DCIS and found that restoration of miR-140 via a genetic approach or with the dietary compound sulforaphane decreased SOX9 and ALDH1, and reduced tumor growth in vivo. These results support that a miR-140/ALDH1/SOX9 axis is critical to basal CSC self-renewal and tumor formation in vivo, suggesting that the miR-140 pathway may be a promising target for preventative strategies in patients with basal-like DCIS.}, } @article {pmid23751479, year = {2013}, author = {Liu, DY and Xie, GR and Chen, M}, title = {[Analysis on the clinical and prognostic features of 71 male patients with breast cancer].}, journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi}, volume = {34}, number = {2}, pages = {187-190}, pmid = {23751479}, issn = {0254-6450}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/diagnosis/metabolism/*pathology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {OBJECTIVE: Male breast cancer (MBC) is a rare disease, with clinical and prognostic features still controversial. The aim of this study was to discuss the clinical characteristics and prognosis of MBC.

METHODS: Clinical data related to 71 MBC patients was reviewed.

RESULTS: The radio of MBC to female breast cancer (FBC) was 42:10 000. Age related to the diagnosis of MBC ranged from 43 to 84 years with the median age as 62 years old, older than the FBC patients (t = 6.355, P = 0.000). The percentage of invasive ductal carcinoma in MBC patients was much higher than in FBC patients (χ(2) = 29.875, P = 0.000). The positive rate of estrogen receptor (ER) was significantly higher than those in FBC patients and the positive rates of human epidermal growth factor receptor-2 (HER-2) were less frequently (χ(2) = 3.741, P = 0.048 and χ(2) = 12.845, P = 0.002) seen. Data from the univariate and multivariate analysis showed that the 3-, 5- and 10-year survival rates of MBC were 82.6%, 74.0% and 47.4% respectively, significantly higher than those in FBC patients (P = 0.004, P = 0.046). Patients with positive HER-2 showed worse prognosis than HER-2 negative patients in MBC patients (χ(2) = 4.219, P = 0.040).

CONCLUSION: There were significant clinic-pathologic and prognostic differences between FBC and MBC patients. The HER-2 positivity seemed to be an important factor for the prognosis and treatment of patients with MBC.}, } @article {pmid23742135, year = {2014}, author = {Atwood, SE and O'Rourke, JA and Peiffer, GA and Yin, T and Majumder, M and Zhang, C and Cianzio, SR and Hill, JH and Cook, D and Whitham, SA and Shoemaker, RC and Graham, MA}, title = {Replication protein A subunit 3 and the iron efficiency response in soybean.}, journal = {Plant, cell & environment}, volume = {37}, number = {1}, pages = {213-234}, doi = {10.1111/pce.12147}, pmid = {23742135}, issn = {1365-3040}, mesh = {Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gene Silencing ; Genome, Plant/*genetics ; *Iron Deficiencies ; Models, Biological ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; Plant Proteins/metabolism ; Protein Binding ; Replication Protein A/genetics/*metabolism ; Soybeans/genetics/*physiology ; Stress, Physiological ; Symbiosis ; }, abstract = {In soybean [Glycine max (L.) Merr.], iron deficiency results in interveinal chlorosis and decreased photosynthetic capacity, leading to stunting and yield loss. In this study, gene expression analyses investigated the role of soybean replication protein A (RPA) subunits during iron stress. Nine RPA homologs were significantly differentially expressed in response to iron stress in the near isogenic lines (NILs) Clark (iron efficient) and Isoclark (iron inefficient). RPA homologs exhibited opposing expression patterns in the two NILs, with RPA expression significantly repressed during iron deficiency in Clark but induced in Isoclark. We used virus induced gene silencing (VIGS) to repress GmRPA3 expression in the iron inefficient line Isoclark and mirror expression in Clark. GmRPA3-silenced plants had improved IDC symptoms and chlorophyll content under iron deficient conditions and also displayed stunted growth regardless of iron availability. RNA-Seq comparing gene expression between GmRPA3-silenced and empty vector plants revealed massive transcriptional reprogramming with differential expression of genes associated with defense, immunity, aging, death, protein modification, protein synthesis, photosynthesis and iron uptake and transport genes. Our findings suggest the iron efficient genotype Clark is able to induce energy controlling pathways, possibly regulated by SnRK1/TOR, to promote nutrient recycling and stress responses in iron deficient conditions.}, } @article {pmid23741999, year = {2013}, author = {Ahn, SJ and Kim, YS and Kim, EY and Park, HK and Cho, EK and Kim, YK and Sung, YM and Choi, HY}, title = {The value of chest CT for prediction of breast tumor size: comparison with pathology measurement.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {130}, pmid = {23741999}, issn = {1477-7819}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/surgery ; Carcinoma, Lobular/*diagnostic imaging/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; *Radiography, Thoracic ; Retrospective Studies ; *Tomography, X-Ray Computed ; Young Adult ; }, abstract = {BACKGROUND: Little information is available on the use of chest computed tomography (CT) to predict breast tumor size in breast cancer, despite the fact that chest CT examinations are being increasingly used. The purpose of this study was to evaluate the value of chest CT for predicting breast tumor size using pathology measurements as reference standards.

METHODS: Tumor sizes (defined as greatest diameter) were retrospectively measured on the preoperative chest CT images of 285 patients with surgically proven unifocal, invasive breast carcinoma. Greatest tumor diameters as determined by chest CT and pathologic examinations were compared by linear regression and Spearman's rho correlation analysis. Concordance between CT and pathology results was defined as a diameter difference of <5 mm. Subgroup analyses were also performed with respect to tumor size (<20 mm or ≥20 mm) and histological subtype (invasive ductal carcinoma(IDC) or non-IDC).

RESULTS: CT and pathology measured diameters were found to be linearly related (size at pathology = 1.086 × CT determined tumor size - 1.141; Spearman's rho correlation coefficient = 0.84, P<0.001). Most tumors (n = 228, 80.0%) were concordant by chest CT and pathology, but 36 tumors (12.7%) were underestimated by CT (average underestimation, 11 mm; range, 6-36 mm) and 21 tumors (7.4%) were overestimated (average overestimation by CT, 10 mm; range, 6-19 mm). The concordance rate between the two sets of measurements was greater for tumor of <20 mm and for IDC (P<0.001 and P = 0.011, respectively).

CONCLUSIONS: Tumor size by chest CT is well correlated with pathology determined tumor size in breast cancer patients, and the diameters of the majority of tumors by chest CT and pathology differed by <5 mm. In addition, the concordance rate was higher for breast tumors of <20 mm and for tumors of the IDC histologic subtype.}, } @article {pmid23739738, year = {2013}, author = {Oki, Y and Onoyama, H and Nikaido, M and Iinuma, S and Endo, K and Tomita, Y and Mizuno, K and Yasui, H}, title = {[Pancreatic cancer in a patient with congenital agenesis of the dorsal pancreas].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {110}, number = {6}, pages = {1044-1053}, pmid = {23739738}, issn = {0446-6586}, mesh = {Aged ; Carcinoma, Ductal/*complications ; Humans ; Male ; Pancreas/*abnormalities ; Pancreatic Neoplasms/*complications ; }, abstract = {A 65-year-old man with back pain showed a hypovascular lesion of the head of the pancreas on dynamic computed tomography and abdominal ultrasonography. The distal portion of the pancreas was not visible. Endoscopic retrograde cholangiopancreatography revealed pancreatic duct obstruction, and the duodenal minor papilla was not visible. Therefore, we diagnosed the patient's condition as stage IVa pancreatic cancer with congenital agenesis of the dorsal pancreas. The patient underwent successful chemotherapy with 3 courses of gemcitabine and S-1, which was followed by pancreaticoduodenectomy. Pathological staging revealed invasive ductal carcinoma, pT3, pN0, pM0, stage III. We report a rare case of pancreatic cancer with congenital agenesis of the dorsal pancreas.}, } @article {pmid23738706, year = {2013}, author = {Song, Y and Liu, X and Zhang, G and Song, H and Ren, Y and He, X and Wang, Y and Zhang, J and Zhang, Y and Sun, S and Liang, X and Sun, Q and Pang, D}, title = {Unique clinicopathological features of metaplastic breast carcinoma compared with invasive ductal carcinoma and poor prognostic indicators.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {129}, pmid = {23738706}, issn = {1477-7819}, mesh = {Adenocarcinoma/mortality/pathology/therapy ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/pathology/therapy ; Carcinoma, Squamous Cell/mortality/pathology/therapy ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Metaplasia/*mortality/pathology/therapy ; Middle Aged ; Neoplasm Recurrence, Local/*mortality/pathology/therapy ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Metaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma.

METHODS: The cases of 55 patients with metaplastic breast carcinoma presenting between 1991 and 2006 were analyzed and compared to the cases of 767 age-matched patients with invasive ductal carcinoma from the same time period.

RESULTS: The group of patients with metaplastic breast carcinoma presented with a larger tumor size, lower lymph node involvement, higher percentage of triple-negative (estrogen receptor-, progesterone receptor- and human epidermal growth factor receptor-2-negative) cases, and Ki-67 over-expression compared with the group of patients with invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Patients in the metaplastic breast carcinoma group tended to have more local (often chest wall) recurrences (P = 0.038) and distant (often lung) metastases (P = 0.001) than those in the invasive ductal carcinomas group. The prognosis of metaplastic breast carcinoma was poorer than that of invasive ductal carcinoma and triple-negative invasive ductal carcinomas; the 5-year overall survival rate was 54.5% in metaplastic breast carcinoma versus 85.1% in invasive ductal carcinoma, and 73.3% in triple-negative invasive ductal carcinomas (P <0.001). The 5-year disease-free survival rate was 45.5% in metaplastic breast carcinoma versus 71.2% in invasive ductal carcinoma, and 60.3% in triple-negative invasive ductal carcinomas (P <0.001). Multivariate analysis revealed tumor size larger than 5.0 cm, lymph node involvement and Ki-67≥14% were significantly related to 5-year overall survival (P = 0.010; P = 0.010; P = 0.035) and 5-year disease-free survival (P = 0.020; P = 0.018; P = 0.049).

CONCLUSIONS: Metaplastic breast carcinoma shows a poorer prognosis than both invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Tumor size larger than 5.0 cm, lymph node involvement and Ki-67 ≥14% indicate a poor prognosis in patients with metaplastic breast carcinoma.}, } @article {pmid23734899, year = {2013}, author = {Angarita, FA and Rodríguez, JL and Meek, E and Sánchez, JO and Tawil, M and Torregrosa, L}, title = {Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {128}, pmid = {23734899}, issn = {1477-7819}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bone Neoplasms/secondary/therapy ; Breast Neoplasms/*diagnosis/therapy ; Carboplatin/administration & dosage ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Carcinoma, Neuroendocrine/*diagnosis/therapy ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Diagnosis, Differential ; Etoposide/administration & dosage ; Female ; Humans ; Liver Neoplasms/secondary/therapy ; Lung Neoplasms/secondary/therapy ; Magnetic Resonance Imaging ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel/administration & dosage ; Prognosis ; Review Literature as Topic ; }, abstract = {BACKGROUND: Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor.

CASE PRESENTATION: We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis.

CONCLUSION: The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.}, } @article {pmid23729783, year = {2013}, author = {Chen, JQ and Bao, Y and Lee, J and Murray, JL and Litton, JK and Xiao, L and Zhou, R and Wu, Y and Shen, XY and Zhang, H and Sahin, AA and Katz, RL and Bondy, ML and Berinstein, NL and Hortobagyi, GN and Radvanyi, LG}, title = {Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {24}, number = {10}, pages = {2534-2542}, pmid = {23729783}, issn = {1569-8041}, support = {1 P50 CA 116199-01/CA/NCI NIH HHS/United States ; CA 16672/CA/NCI NIH HHS/United States ; KG080061//PHS HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/drug therapy/*mortality/*pathology ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology ; DNA-Binding Proteins/*metabolism ; Disease-Free Survival ; *Epithelial-Mesenchymal Transition ; Estrogen Receptor alpha/metabolism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry/methods ; Ki-67 Antigen/metabolism ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Repressor Proteins ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: TRPS-1 is a new GATA transcription factor that is differentially expressed in breast cancer (BC) where it been found recently to regulate epithelial-to-mesenchymal transition (EMT).

PATIENTS AND METHODS: We carried out a quantitative immunohistochemistry (qIHC) analysis of TRPS-1 expression in 341 primary-stage I-III BC samples in relation to patient clinical characteristics as well as its prognostic value, especially in an estrogen receptor-positive (ER+) subgroup.

RESULTS: Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics as well as with improved overall survival (OS) and disease-free survival (DFS). Among stage I/II ER+ BC patients who received endocrine therapy alone, those with high TRPS-1 expression had significantly longer OS and DFS. There was also a strong association between TRPS-1 levels and the EMT marker E-cadherin in the ER+ invasive ductal carcinoma cases. Analysis of gene expression data on a panel of BC lines found that TRPS-1 expression was low or absent in BC lines having enriched mesenchymal features.

CONCLUSIONS: Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy.}, } @article {pmid23729369, year = {2013}, author = {Guo, HQ and Zhang, ZH and Zhao, H and Zhao, LL and Pan, QJ}, title = {Recognizing breast ductal carcinoma in situ on fine-needle aspiration: a diagnostic dilemma.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {8}, pages = {710-715}, doi = {10.1002/dc.23015}, pmid = {23729369}, issn = {1097-0339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {In this study, we evaluated cytomorphologic features of different subgroups of ductal carcinoma in situ (DCIS); we compared seven cytologic features between DCIS and invasive ductal carcinoma (IDC) aspirates to determine whether diagnosis of stromal invasion can be made based on fine-needle aspiration (FNA) findings. There were 142 cases of DCIS and 1,978 cases of IDC enrolled in our study. FNA analysis revealed 80.3% sensitivity for DCIS and 94.7% sensitivity for IDC. High and intermediate grade DCIS exhibited marked nuclear abnormality (92.1% vs. 35.7%, 30.0%; P1 < 0.001, P2 < 0.001) and necrosis (69.7% vs. 0%, 10.0%; P1 < 0.001, P2 = 0.001) in a higher percentage of cases compared to low grade DCIS and intraductal/intracystic papillary carcinoma. The rates of background macrophages (71.3% for DCIS and 21.9% for IDC, P < 0.001) and extensive necrosis (54.0% for DCIS and 16.7% for IDC, P < 0.001) were significantly higher in DCIS compared to IDC. Lymphocytes were observed in conjunction with tumor cells more frequently in IDC (81.3%) compared to DCIS (36.8%, P < 0.001). Stromal fragments associated with tumor cells were only observed in invasive lesions (11.9% micro-invasive DCIS and 52.1% IDC). Tubular structures were found exclusively in IDC (11.5%). Cytologic criteria for diagnosis of high and low grade DCIS are different. The suspicion of DCIS is raised when background macrophages and extensive necrosis are observed. Stromal invasion is suggested by FNA if lymphocytes are entwined around tumor cells or if stromal fragments associated with tumor cells or tubular structures are observed.}, } @article {pmid23725071, year = {2013}, author = {Monsefi, N and Nikpour, H and Safavi, M and Lashkarizadeh, MR and Dabiri, S}, title = {Mucinous subtype of invasive ductal carcinoma arising within a fibroadenoma.}, journal = {Archives of Iranian medicine}, volume = {16}, number = {6}, pages = {366-368}, pmid = {23725071}, issn = {1735-3947}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Fibroadenoma/*pathology ; Humans ; Mammography ; Middle Aged ; }, abstract = {Fibroadenoma is a common benign tumor observed during the second and third decades of life. Malignancy transformation in the epithelial component of a fibroadenoma is rare and can occur 20 years after its diagnosis. Mammographic findings in this phenomenon include indistinct margins and microcalcifications. Here we present a 58-year-old woman with a mobile, lateral upper quadrant mass that was rather firm when palpated. The mammography showed a lobulated mass without calcification suggestive of a benign process, most probably fibroadenoma. However the excisional biopsy contained both an intracanalicular fibroadenoma and invasive ductal carcinoma with mucinous components.}, } @article {pmid23719622, year = {2013}, author = {Saguy, T and Dovidio, JF}, title = {Insecure status relations shape preferences for the content of intergroup contact.}, journal = {Personality & social psychology bulletin}, volume = {39}, number = {8}, pages = {1030-1042}, doi = {10.1177/0146167213487078}, pmid = {23719622}, issn = {1552-7433}, mesh = {Adult ; *Attitude ; *Communication ; Female ; Humans ; *Interpersonal Relations ; Male ; *Social Class ; }, abstract = {Recent work demonstrated that whereas high-status and low-status group members seek to address cross-group commonalities during intergroup contact, members of low-status groups show a greater desire to discuss status differences between the groups. Drawing on social identity theory, the current research investigated the combined influence of status legitimacy and status stability on these contact preferences. In Study 1, perceived stability and perceived legitimacy were measured among members of a high-status ethnic group in Israel. In Study 2, group status, status stability, and status legitimacy were experimentally manipulated in a U.S. sample. Although they generally preferred to discuss commonalities over status differences, across studies high-status group members' willingness to discuss status differences increased when they perceived the hierarchy as illegitimate but stable. By contrast, low-status group members were particularly inclined to address status differences and least interested in discussing commonalties, when the hierarchy was illegitimate and unstable.}, } @article {pmid23718612, year = {2013}, author = {Hu, C and Wang, J and Zheng, C and Xu, S and Zhang, H and Liang, Y and Bi, L and Fan, Z and Han, B and Xu, W}, title = {Raman spectra exploring breast tissues: comparison of principal component analysis and support vector machine-recursive feature elimination.}, journal = {Medical physics}, volume = {40}, number = {6}, pages = {063501}, doi = {10.1118/1.4804054}, pmid = {23718612}, issn = {2473-4209}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/*diagnosis ; Diagnosis, Computer-Assisted/*methods ; Female ; Humans ; Pattern Recognition, Automated/*methods ; *Principal Component Analysis ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrum Analysis, Raman/*methods ; *Support Vector Machine ; }, abstract = {PURPOSE: Raman spectroscopy was explored to diagnose normal, benign, and malignant human breast tissues based on principal component analysis (PCA) and support vector machine-recursive feature elimination (SVM-RFE), and SVM-RFE results were compared with PCA.

METHODS: 1800 Raman spectra were acquired from fresh samples of human breast tissues (normal, fibroadenoma, adenosis, galactoma, and invasive ductal carcinoma) from 168 patients. After set up the SVM-RFE and PCA models, Mahalanobis distance, spectral residuals, sensitivity, specificity, and Matthews correlation coefficient (MCC) were used as the discriminating criteria for evaluating these two methods.

RESULTS: The comparison shows that SVM-RFE based on the selection of characteristic peaks better reflects the nature of biopsy and it produces better discrimination, sensitivity, specificity, and MCC for normal (1, 1, 1), malignant (0.93, 0.97, 0.91), and benign (0.95, 0.97, 0.91) breast tissues.

CONCLUSIONS: The Raman spectroscopy combined with SVM-RFE opens great future in the clinical applications of mammary disease diagnosis.}, } @article {pmid23717338, year = {2013}, author = {Abou-Bakr, AA and Eldweny, HI}, title = {p16 expression correlates with basal-like triple-negative breast carcinoma.}, journal = {Ecancermedicalscience}, volume = {7}, number = {}, pages = {317}, pmid = {23717338}, issn = {1754-6605}, abstract = {BACKGROUND: Basal-like breast carcinoma (BLBC) has attracted considerable attention over the past few years. It has been suggested that tumours expressing basal markers have a more aggressive clinical behaviour. However, a molecular basis for this disease remains unclear, and it lacks currently used therapeutic targets. Therefore developing a novel treatment strategy is crucial for improving the prognosis. The aim of this study was to characterise the immunohistochemical (IHC) expression of p16 in patients with BLBC compared with non-BLBC.

MATERIALS AND METHODS: Eighty-five cases of grade-3 invasive ductal carcinomas not otherwise specified (IDC-NOS) were analyzed. Immunohistochemical stains for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and p16 were performed. BLBC was defined as ER-, PR-, Her2- and CK5/6+, and/or EGFR+.

RESULTS: Twenty cases were categorised as BLBC versus 65 as non-basal. High mitotic count and presence of necrosis were associated with basal-like phenotype. Distant metastasis developed in 40% of cases of BLBC with frequent spread to brain and lung. p16 had significantly higher expression in the basal subgroup (80% versus 50.8%, P = 0.04). Patients with BLBCs were found to have a lower disease-free survival (DFS) rate (60% versus 70.8%, P = 0.03).

CONCLUSION: BLBC typically demonstrates a unique profile. p16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome.}, } @article {pmid23714006, year = {2013}, author = {Gokce, H and Durak, MG and Akin, MM and Canda, T and Balci, P and Ellidokuz, H and Demirkan, B and Gorken, IB and Sevinc, AI and Kocdor, MA and Saydam, S and Harmancioglu, O}, title = {Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.}, journal = {The breast journal}, volume = {19}, number = {4}, pages = {374-381}, doi = {10.1111/tbj.12128}, pmid = {23714006}, issn = {1524-4741}, mesh = {Adult ; Aged ; Axilla/pathology ; Breast Neoplasms/metabolism/*mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/pathology ; Carcinoma, Papillary/metabolism/*mortality/*pathology ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sentinel Lymph Node Biopsy ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.}, } @article {pmid23712790, year = {2013}, author = {Lal, A and Chan, L and Devries, S and Chin, K and Scott, GK and Benz, CC and Chen, YY and Waldman, FM and Hwang, ES}, title = {FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast.}, journal = {Breast cancer research and treatment}, volume = {139}, number = {2}, pages = {381-390}, doi = {10.1007/s10549-013-2556-4}, pmid = {23712790}, issn = {1573-7217}, support = {R21 CA155679/CA/NCI NIH HHS/United States ; P50 CA58207/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/immunology/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/immunology/*metabolism/*pathology ; Disease Progression ; Epithelium/metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Stromal Cells/metabolism ; T-Lymphocytes, Regulatory/immunology/*metabolism ; p21-Activated Kinases/metabolism ; }, abstract = {FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with cancer progression. We evaluated quantitative FOXP3 expression in lymphocytes as well as in epithelial cells in a set of thirty-two breast tumors with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Tumors were stained for FOXP3 and CD3 expression and Tregs quantified by determining the ratio of colocalized FOXP3 and CD3 relative to 1) total CD3-expressing lymphocytes and 2) to FOXP3-expressing epithelial cells. The median proportion of FOXP3-expressing CD3 cells significantly increased with malignant progression from normal to DCIS to IDC components (0.005, 0.019 and 0.030, respectively; p ≤ 0.0001 for normal vs. IDC and p = 0.004 for DCIS vs. IDC). The median intensity of epithelial FOXP3 expression was also increased with invasive progression and most markedly augmented between normal and DCIS components (0.130 vs. 0.175, p ≤ 0.0001). Both Treg infiltration and epithelial FOXP3 expression were higher in grade 3 vs. grade 1 tumors (p = 0.014 for Tregs, p = 0.038 for epithelial FOXP3), but did not vary significantly with hormone receptor status, size of invasive tumor, lymph node status, or disease stage. Notably, Treg infiltration significantly correlated with epithelial up-regulation of FOXP3 expression (p = 0.013 for normal, p = 0.001 for IDC). These findings implicate both Treg infiltration and up-regulated epithelial FOXP3 expression in breast cancer progression.}, } @article {pmid23710913, year = {2013}, author = {Liu, F and Niu, Y and Liu, N and Zhang, W and Wang, SL and Liu, H and Zhang, TX}, title = {[Expression of vacuole membrane protein 1 and its prognostic value in invasive ductal carcinoma of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {42}, number = {2}, pages = {86-89}, doi = {10.3760/cma.j.issn.0529-5807.2013.02.004}, pmid = {23710913}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Membrane Proteins/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the expression of vacuole membrane protein 1 (Vmp1) and its prognostic value in invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS) of the breast.

METHODS: The expression and location of Vmp1 in the breast tissues from 102 patients with IDC and 32 concomitant DCIS were detected by immunohistochemical SP method, and the relationship with clinicopathologic parameters was analyzed.

RESULTS: Vmp1 expression was observed in the cytoplasm of the cancer cells in 57.8% (59/102) cases, and correlated with grade (χ(2) = 12.644, P = 0.002), pTNM stage (χ(2) = 11.987, P = 0.001), node status (χ(2) = 9.341, P = 0.002), tumor diameter (χ(2) = 7.630, P = 0.022) as well as Nottingham Prognostic Index (NPI;χ(2) = 15.561, P = 0.000). The expression of Vmp1 in concomitant DCIS was higher than that in IDC (81.3% vs 56.3%; χ(2) = 4.655, P = 0.031). In this cohort, the mean disease-free survival was 81.2 months; the 5-year overall survival rate was 90.2% (92/102) and the disease-free survival rate was 81.4% (83/102). Vmp1 expression had significant influence on disease-free survival time, with Vmp1-negative patients showing poor prognosis (χ(2) = 11.192, P = 0.001). COX's proportional hazards regression model revealed that Vmp1 was a protective factor, with relative risk < 1.

CONCLUSIONS: The detection of Vmp1 in IDC may be helpful for prognosis prediction; the patients with Vmp1 expression may have a better prognosis.}, } @article {pmid23707342, year = {2013}, author = {de Craen, S and Vlakveld, WP}, title = {Young drivers who obtained their licence after an intensive driving course report more incidents than drivers with a traditional driver education.}, journal = {Accident; analysis and prevention}, volume = {58}, number = {}, pages = {64-69}, doi = {10.1016/j.aap.2013.03.037}, pmid = {23707342}, issn = {1879-2057}, mesh = {Accidents, Traffic/*prevention & control/statistics & numerical data ; Adolescent ; Automobile Driver Examination/statistics & numerical data ; Automobile Driving/*education ; Education/*methods ; Female ; Humans ; Licensure ; Male ; Netherlands ; Surveys and Questionnaires ; Time Factors ; Young Adult ; }, abstract = {This paper studies the effectiveness of intensive driving courses; both in driving test success and safe driving after passing the driving test. The so-called intensive driving course (IDC) consists of a limited number of consecutive days in which the learner driver takes driving lessons all day long; and is different from traditional training in which lessons are spread out over several months and in which learners take one or two driving lessons of approximately 1 h each per week. Our study indicates that--in the first two years of their driving career--IDC drivers (n=35) reported an incident significantly more often (43%) than 351 drivers who obtained their driving licence after traditional training (26%). Our study also indicates that the IDC drivers underwent almost the same number of training hours as the drivers who had traditional training, although spacing of these hours was different. There was no difference in the number of attempts to pass the driving test. We did not find any evidence that a self-selection bias was responsible for the difference in reported number of incidents.}, } @article {pmid23704896, year = {2013}, author = {Colak, D and Nofal, A and Albakheet, A and Nirmal, M and Jeprel, H and Eldali, A and Al-Tweigeri, T and Tulbah, A and Ajarim, D and Malik, OA and Inan, MS and Kaya, N and Park, BH and Bin Amer, SM}, title = {Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63204}, pmid = {23704896}, issn = {1932-6203}, mesh = {Adult ; Aging/*genetics/pathology ; Animals ; Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinogenesis/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cohort Studies ; Computational Biology ; *Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks/genetics ; Genes, Neoplasm/genetics ; Genome, Human/genetics ; Humans ; Immunohistochemistry ; Mice ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Species Specificity ; *Transcriptome ; Young Adult ; }, abstract = {Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.}, } @article {pmid23704429, year = {2013}, author = {Takhar, AS and Ney, A and Patel, M and Sharma, A}, title = {Extramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancer.}, journal = {BMJ case reports}, volume = {2013}, number = {}, pages = {}, pmid = {23704429}, issn = {1757-790X}, mesh = {Antineoplastic Agents/*therapeutic use ; Axilla/pathology/surgery ; Biopsy ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Cytodiagnosis ; Female ; *Hematopoiesis, Extramedullary ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis/*diagnosis ; *Megakaryocytes ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; }, abstract = {We report the case of a 53-year-old lady who presented with a lump in her left breast. Her initial investigations demonstrated a grade III invasive ductal carcinoma of the breast that was tethered to the pectoralis major; imaging and cytology also revealed metastatic nodes in the left axilla. After undergoing neoadjuvant chemotherapy with evidence of clinical and radiological tumour response, a wire-guided wide local excision and axillary node clearance was performed. When a histological analysis of the specimen was performed, there was no evidence of a viable metastatic tumour in the axillary lymph nodes, but there were several areas of extramedullary haematopoiesis. There are only two other reports in the literature of this finding. This could represent a potential source of false-positive diagnosis of axillary metastasis from breast cancer. It would be prudent to consider biopsy prior to clearance if there are megakaryocytes in axillary node cytology.}, } @article {pmid23703345, year = {2013}, author = {Bhatia, A and Dey, P and Goel, S and Singh, G}, title = {Expression of γH2AX may help in defining a genetically more stable subtype of infiltrating ductal carcinoma of breast.}, journal = {The Indian journal of medical research}, volume = {137}, number = {4}, pages = {759-766}, pmid = {23703345}, issn = {0975-9174}, mesh = {Adult ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinogenesis/genetics ; Carcinoma, Ductal/*genetics/pathology ; Female ; Fibroadenoma/*genetics/pathology ; Gene Expression Regulation, Neoplastic ; Histones/*biosynthesis/genetics ; Humans ; Prognosis ; }, abstract = {BACKGROUND & OBJECTIVES: Gamma H2AX, a marker of DNA double stranded breaks (DSB) has been found to be over expressed in various tumours. The objective of the present work was to study the expression of γH2AX in infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) cases and to associate the expression in IDC with cytomorphological features and DNA ploidy.

METHODS: The expression of γH2AX was studied in fine needle aspirates of 16 cases of IDC and 15 FA cases. The expression in IDC was correlated with the cytological grade, apoptotic (AI) and mitotic indices (MI) and ploidy status.

RESULTS: A high γH2AX expression was noted in IDC as compared to FA. Amongst the IDC cases the γH2AX was found to be significantly over expressed in DNA diploid IDC cases as compared to the aneuploid ones.

The study suggests a role of γH2AX in breast carcinogenesis which needs to be explored further. Moreover, the γH2AX expression together with ploidy status may serve as a means of assigning the patients of IDC to a better prognostic category irrespective of the cytomorphogical parameters.}, } @article {pmid23702653, year = {2014}, author = {Mrklić, I and Pogorelić, Z and Ćapkun, V and Tomić, S}, title = {Expression of topoisomerase II-α in triple negative breast cancer.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {22}, number = {3}, pages = {182-187}, doi = {10.1097/PAI.0b013e3182910967}, pmid = {23702653}, issn = {1533-4058}, mesh = {Anthracyclines/*pharmacology/therapeutic use ; Antigens, Neoplasm/metabolism ; Antineoplastic Agents/*pharmacology/therapeutic use ; Breast Neoplasms/*diagnosis/drug therapy/mortality ; Carcinoma/*diagnosis/drug therapy/mortality ; DNA Topoisomerases, Type II/metabolism ; DNA-Binding Proteins/*antagonists & inhibitors/metabolism ; Estrogen Receptor alpha/metabolism ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Phenotype ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; Up-Regulation ; }, abstract = {Triple negative breast cancer (TNBC)-defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity is a group with poor prognosis, due to aggressive tumor biology and lack of targeted therapy. Topoisomerase II-α (topoIIα) protein is one of the intracellular targets for anthracycline-based therapy, and high levels of topoIIα expression are recently observed in TNBC. The study included 83 patients who underwent surgery between January 2003 and December 2009. Paraffin blocks were stained immunohistochemically with CK5/6, CK14, EGFR, Ki-67, and topoIIα. Basal-like (BL) immunophenotype was defined by positivity for ≥1 basal cell markers: CK5/6, CK14, or EGFR. Of 83 TNBC, 66.26% were of the BL immunophenotype, which was significantly associated with higher mitotic count (P=0.023), BL morphology (P=0.005), higher histologic grade (P=0.022), and higher proliferation rate assessed by Ki-67 (P<0.001). TopoIIα expression was significantly correlated with invasive ductal carcinoma NOS (P=0.010), higher mitotic count (P=0.001), higher histologic grade (P=0.007), and higher Ki-67 (P<0.001). In conclusion, due to lack of expression of ER, PR, and human epidermal growth factor receptor 2 receptor in TNBC, specific targeted therapies are not effective, and chemotherapy is currently the only modality of available systemic therapy. Due to expression of topoIIα, anthracyclines may be effective in treatment of TNBC.}, } @article {pmid23700260, year = {2013}, author = {Byun, BH and Noh, WC and Lim, I and Lee, SS and Cho, AR and Park, JA and Kim, KM and Kim, HA and Kim, EK and Kim, BI and Choi, CW and Lim, SM}, title = {A new method for apparent diffusion coefficient measurement using sequential (18)F-FDG PET and MRI: correlation with histological grade of invasive ductal carcinoma of the breast.}, journal = {Annals of nuclear medicine}, volume = {27}, number = {8}, pages = {720-728}, doi = {10.1007/s12149-013-0737-1}, pmid = {23700260}, issn = {1864-6433}, mesh = {Adult ; Biological Transport ; Breast Neoplasms/diagnostic imaging/*metabolism/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*metabolism/*pathology ; Diffusion ; Feasibility Studies ; Female ; *Fluorodeoxyglucose F18/metabolism ; Humans ; *Magnetic Resonance Imaging ; Multimodal Imaging/*methods ; Neoplasm Grading ; Neoplasm Invasiveness ; Observer Variation ; *Positron-Emission Tomography ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to measure the apparent diffusion coefficient (ADC) value at the region with the highest FDG uptake using sequential (18)F-FDG PET and MRI, and to correlate it with the histological grade of invasive ductal carcinoma (IDC) of the breast.

METHODS: A retrospective study was conducted on 75 untreated patients with IDC. First, a PET/CT scan and subsequent breast MRI were done and the SUVmax of the each breast tumor was recorded. Then, a PET image and ADC map were co-registered. On the axial slice containing the pixel with SUVmax, we drew multiple circular ROIs within the tumor and measured the mean ADC value of each ROI. The average (ADC-mean) and minimum (ADC-min) of the mean ADC values for all ROIs within the tumor were calculated, respectively. Then, a circular ROI was placed at the corresponding location to the pixel with the highest SUV and the mean ADC value of the ROI was denoted as ADC-PET. We compared the averages of the ADC parameters and assessed the correlations among SUVmax and ADC parameters. ROC curve and logistic regression analyses were performed to assess the utility of ADC and SUVmax for detecting histological grade 3.

RESULTS: ADC-min was significantly lower than the ADC-mean or ADC-PET. All of the ADC parameters showed a negative correlation with SUVmax. The area under the ROC curve for identifying histological grade 3 using ADC-PET, ADC-min, ADC-mean and SUVmax was 0.684, 0.660, 0.633 and 0.639, respectively. By multivariate analysis, ADC-PET was a significant, independent predictor of histological grade 3 (p = 0.004).

CONCLUSIONS: We estimated the ADC value at the breast tumor region with the highest FDG uptake using sequential (18)F-FDG PET and MRI. This new ADC parameter distinguished high-grade IDC, supporting the feasibility of the combined PET-MRI system in patients with breast cancer.}, } @article {pmid23696929, year = {2013}, author = {Arnutti, P and Kotepui, M and Asanprakit, W and Punyarit, P and Chavalitshewinkoon-Petmitr, P and Harnroongroj, T and Petmitr, S}, title = {Determination of whole transcription profiles and specific pathways in invasive ductal breast carcinoma.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {6}, pages = {1112-1120}, pmid = {23696929}, issn = {1936-2625}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Female ; *Gene Expression Profiling/methods ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; Genetic Testing/*methods ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; }, abstract = {Breast cancer is the most common cancer affecting women worldwide including Thailand. Whole transcription profiles of invasive ductal breast carcinoma (IDC) obtained by oligonucleotide microarray should lead to a better understanding of the molecular basis of IDCs, allow for examination of specific markers for diagnosis, and provide novel targets for therapy. This study aimed to detect the whole transcript expression of approximately 35,000 target genes in Thai breast cancer patients, using Affymetrix GeneChip(®) Exon 1.0 Sense Target Arrays. Analysis revealed that the differential expression profiles of 928 genes (423 up-regulated and 505 down-regulated genes) were 2-fold or greater (unpaired t-test, p < 0.05) in invasive ductal breast cancer, compared with normal tissues. The Gene Ontology (GO) databases support important associations in 17 gene sets with p-value < 1E-10 and ≥ 4-fold changes, involving the tumorigenic pathways of cell cycles, extracellular regions, as well as cellular component organization. Likewise, the TGFBR and IL-6 pathways contain gene expression with statistically significant changes in IDC.}, } @article {pmid23695798, year = {2013}, author = {Otsuka, T and Morizane, C and Nara, S and Ueno, H and Kondo, S and Shimada, K and Kosuge, T and Ikeda, M and Hiraoka, N and Okusaka, T}, title = {Gemcitabine in patients with intraductal papillary mucinous neoplasm with an associated invasive carcinoma of the pancreas.}, journal = {Pancreas}, volume = {42}, number = {5}, pages = {889-892}, doi = {10.1097/MPA.0b013e3182826f1f}, pmid = {23695798}, issn = {1536-4828}, mesh = {Adenocarcinoma, Mucinous/*drug therapy/surgery ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/surgery ; Carcinoma, Papillary/*drug therapy/surgery ; Chi-Square Distribution ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms/*drug therapy/surgery ; Time Factors ; Treatment Outcome ; Gemcitabine ; }, abstract = {OBJECTIVES: The standard chemotherapy for invasive ductal carcinoma of the pancreas (IDC) is gemcitabine; however, the efficacy of gemcitabine in invasive intraductal papillary mucinous neoplasm with an associated invasive carcinoma of the pancreas (IPMN-IC) is still unknown.

METHODS: Because it is difficult to distinguish between IPMN-IC and IDC based only on radiological findings in advanced unresectable cases, recurrent cases after surgical resection were analyzed to identify the efficacy of gemcitabine monotherapy for IPMN-IC.

RESULTS: Between 1992 and 2010, 128 patients with IPMN-IC and 548 patients with IDC underwent pancreatic resection at the National Cancer Center Hospital. Twelve patients with IPMN-IC and 73 patients with IDC had recurred after surgery and subsequently underwent gemcitabine at the standard dosage. The disease-control rates were comparable between the IPMN-IC and IDC patients (58.3% vs 59.4%). The median progression-free survival was 2.8 and 4.1 months in the IPMN-IC and IDC patients, respectively (P = 0.46). Also, no statistically significant difference in the median survival times was observed between the 2 groups (9.3 vs 8.8 months, respectively; P = 0.09).

CONCLUSIONS: Among patients who had IPMN-IC and IDC with recurrent disease after resection, there was no significant difference in treatment outcomes after gemcitabine.}, } @article {pmid23693000, year = {2013}, author = {Jayender, J and Gombos, E and Chikarmane, S and Dabydeen, D and Jolesz, FA and Vosburgh, KG}, title = {Statistical Learning Algorithm for in situ and invasive breast carcinoma segmentation.}, journal = {Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society}, volume = {37}, number = {4}, pages = {281-292}, pmid = {23693000}, issn = {1879-0771}, support = {P41 EB015898/EB/NIBIB NIH HHS/United States ; P41 RR019703/RR/NCRR NIH HHS/United States ; P41RR019703/RR/NCRR NIH HHS/United States ; P41EB015898/EB/NIBIB NIH HHS/United States ; }, mesh = {*Algorithms ; *Artificial Intelligence ; Breast Neoplasms/*pathology ; Data Interpretation, Statistical ; Female ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Markov Chains ; Models, Biological ; Models, Statistical ; Pattern Recognition, Automated/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Dynamic Contrast Enhanced MRI (DCE-MRI) has proven to be a highly sensitive imaging modality in diagnosing breast cancers. However, analyzing the DCE-MRI is time-consuming and prone to errors due to the large volume of data. Mathematical models to quantify contrast perfusion, such as the black box methods and pharmacokinetic analysis, are inaccurate, sensitive to noise and depend on a large number of external factors such as imaging parameters, patient physiology, arterial input function, and fitting algorithms, leading to inaccurate diagnosis. In this paper, we have developed a novel Statistical Learning Algorithm for Tumor Segmentation (SLATS) based on Hidden Markov Models to auto-segment regions of angiogenesis, corresponding to tumor. The SLATS algorithm has been trained to identify voxels belonging to the tumor class using the time-intensity curve, first and second derivatives of the intensity curves ("velocity" and "acceleration" respectively) and a composite vector consisting of a concatenation of the intensity, velocity and acceleration vectors. The results of SLATS trained for the four vectors has been shown for 22 Invasive Ductal Carcinoma (IDC) and 19 Ductal Carcinoma In Situ (DCIS) cases. The SLATS trained for the velocity tuple shows the best performance in delineating the tumors when compared with the segmentation performed by an expert radiologist and the output of a commercially available software, CADstream.}, } @article {pmid23692343, year = {2013}, author = {Bjelogrlic, SK and Lukic, ST and Djuricic, SM}, title = {Activity of dexrazoxane and amifostine against late cardiotoxicity induced by the combination of doxorubicin and cyclophosphamide in vivo.}, journal = {Basic & clinical pharmacology & toxicology}, volume = {113}, number = {4}, pages = {228-238}, doi = {10.1111/bcpt.12086}, pmid = {23692343}, issn = {1742-7843}, mesh = {Amifostine/*pharmacology ; Animals ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Cardiomyopathies/chemically induced/*drug therapy/*prevention & control ; Cardiotonic Agents/pharmacology ; Cyclophosphamide/adverse effects ; Dexrazoxane/*pharmacology ; Doxorubicin/adverse effects ; Drug Combinations ; Female ; Mice ; Mice, Inbred BALB C ; Myocardium/pathology ; }, abstract = {Cardiotoxicity is one of the main limiting side effects of doxorubicin and cyclophosphamide (DC) treatment, and this study was organized to identify cardioprotective activity of amifostine and dexrazoxane against DC combination. BalbC/NIH mice underwent DC treatment (DC group), were pre-treated with amifostine (ADC group) or dexrazoxane (IDC group) and were killed at 1.5 and 3 months after treatments when the grade of myocardial damage was analysed by light microscopy using the Billingham scoring method. DC treatment induced severe myocardial damage with one lethal event before evaluation at 3 months. Main characteristics of DC cardiotoxicity were polymorphic myocyte degeneration and alterations in blood vessels followed by ecchymoses, haemorrhage and thromboses. Polymorphism was also found in the IDC and ADC groups, but its morphological patterns were different. In animals subject to IDC treatment, the blood vessels were better preserved than in the ADC group, whereas thrombosis was not seen in either of these two groups. Quantitatively, grade of myocardial injury in the ADC and IDC groups was significantly higher compared with the non-treated group at both times of estimation and significantly lower compared with the DC group at 1.5 months. At 3 months, significance against DC treatment was lost in the ADC group, while preserved in the IDC-treated animals. Also, there was significant progression in the ADC group comparing scores between 1.5 and 3 months. These results revealed that the cardiotoxicity of DC combination displays specific morphological hallmark and evolution in time, different to those described after doxorubicin single treatment. Neither amifostine nor dexrazoxane prevented development of cardiomyopathy induced by DC treatment.}, } @article {pmid23691479, year = {2012}, author = {Hao, JY and Yang, CC and Liu, FF and Yang, YL and Li, S and Li, WD and Li, YQ and Lang, RG and Fan, Y and Paulos, E and Zhang, XM and Fu, L}, title = {Accessory breast cancer occurring concurrently with bilateral primary invasive breast carcinomas: a report of two cases and literature review.}, journal = {Cancer biology & medicine}, volume = {9}, number = {3}, pages = {197-201}, pmid = {23691479}, issn = {2095-3941}, abstract = {The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise specified, IDC-NOS) and an accessory breast carcinoma (IDC-NOS) incidentally identified in her left axilla. The ectopic breast tissue in her right axilla presented with adenosis. The patient was surgically treated, followed by postoperative docetaxel epirubicin (TE) chemotherapy. The second case was a 53-year-old Chinese female with bilateral breast cancer (apocrine carcinoma) accompanied by an accessory breast carcinoma (IDC-NOS) in her right axilla that was also incidentally identified. The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel (CET) neoadjuvant chemotherapy, followed by adjuvant chemotherapy of the same regimen.}, } @article {pmid23691441, year = {2013}, author = {Zhou, F and Li, S and Meng, HM and Qi, LQ and Gu, L}, title = {MicroRNA and histopathological characterization of pure mucinous breast carcinoma.}, journal = {Cancer biology & medicine}, volume = {10}, number = {1}, pages = {22-27}, pmid = {23691441}, issn = {2095-3941}, abstract = {OBJECTIVE: Pure mucinous breast carcinoma (PMBC) is an uncommon histological type of breast cancer characterized by a large amount of mucin production. MicroRNA (miRNA) is a large class of small noncoding RNA of about 22 nt involved in the regulation of various biological processes. This study aims to identify the miRNA expression profile in PMBC.

METHODS: MiRNA expression profiles in 11 PMBCs were analyzed by miRNA-microarray and real-time polymerase chain reaction (PCR). Thirty-one PMBCs and 27 invasive ductal carcinoma of no special types (IDC-NSTs) were assessed by immunohistochemistry using antibodies against ER, PR-progesterone receptor, HER2, Ki-67, Bcl-2, p53, PCNA, and CK5 and 6.

RESULTS: We analyzed the miRNA expression in 11 PMBCs and corresponding normal tissues using miRNA-microarray and real-time PCR, and found that miR-143 and miR-224-5p were significantly downregulated in mucinous carcinoma tissue. Compared with IDC-NSTs, PMBC showed a significantly higher ER positive rate, lower HER-2 positive rate, and lower cell proliferation rates.

CONCLUSIONS: To our knowledge, this is the first study to demonstrate the miRNA expression profile of PMBC, and our findings may lead to further understanding of this type of breast cancer.}, } @article {pmid23690703, year = {2013}, author = {Chang, ED and Kim, MK and Kim, JS and Whang, IY}, title = {Primary neuroendocrine tumor of the breast: imaging features.}, journal = {Korean journal of radiology}, volume = {14}, number = {3}, pages = {395-399}, pmid = {23690703}, issn = {2005-8330}, mesh = {Adult ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Neuroendocrine/*diagnosis ; Diagnosis, Differential ; Diagnostic Imaging/*methods ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Ultrasonography, Mammary ; }, abstract = {Focal neuroendocrine differentiation can be found in diverse histological types of breast tumors. However, the term, neuroendocrine breast tumor, indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population. The imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type. We present a case of a pathologically confirmed, primary neuroendocrine breast tumor in a 42-year-old woman, with imaging findings difficult to be differentiated from that of invasive ductal carcinoma.}, } @article {pmid23690415, year = {2013}, author = {Hepel, JT and Wazer, DE}, title = {Should a woman age 70 to 80 years receive radiation after breast-conserving surgery?.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {19}, pages = {2377-2381}, doi = {10.1200/JCO.2012.48.3875}, pmid = {23690415}, issn = {1527-7755}, mesh = {Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology/*therapy ; Female ; Humans ; *Mastectomy, Segmental ; Receptors, Estrogen/*analysis ; Tamoxifen/*therapeutic use ; }, abstract = {Case 1: A 72-year-old woman presents with a palpable mass detected during yearly physical examination by her primary care physician. She has controlled hypertension and remains active, playing tennis three times a week. Physical examination reveals a 1.5 cm mass in the upper outer quadrant of the left breast with no palpable axillary lymphadenopathy. Diagnostic imaging reveals a suspicious mass, and core biopsy confirms invasive ductal carcinoma (IDC) that is estrogen receptor moderately positive (60%), progesterone receptor negative and Her2-neu that is not overexpressed. She undergoes a wide local excision and sentinel node biopsy. Pathology reveals a 1.5 cm IDC that is high grade without lymphovascular invasion (LVI). The margins are negative with the closest laterally at 2 mm. One sentinel node is negative for metastasis. Case 2: A 72-year-old woman presents with an abnormal screening mammogram that shows a small area of architectural distortion in the upper outer quadrant of the left breast (Fig 1). She is a former smoker with mild chronic obstructive pulmonary disease and has mild to moderately symptomatic osteoarthritis managed with a nonsteroidal anti-inflammatory agent. She remains active and independent. Physical examination reveals neither palpable breast mass nor axillary lymphadenopathy. Diagnostic ultrasound confirms a 1.8 cm mass, and core biopsy reveals IDC that is estrogen and progesterone receptor strongly positive (> 90%) and Her2-neu that is not overexpressed. She undergoes a wide local excision and sentinel node biopsy. Pathology reveals a 1.9 cm IDC that is low grade. The margins are widely negative at > 5 mm and there is no LVI. One sentinel node is negative for metastasis.}, } @article {pmid23686806, year = {2013}, author = {Zhao, T and Miao, Z and Wang, Z and Xu, Y and Wu, J and Liu, X and You, Y and Li, J}, title = {Overexpression of CRKL correlates with malignant cell proliferation in breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {34}, number = {5}, pages = {2891-2897}, pmid = {23686806}, issn = {1423-0380}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/genetics/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; *Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; }, abstract = {Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. However, the expression pattern of CRKL protein and its clinical significance in human breast cancers have not been well characterized. In this study, expression of CRKL was evaluated in 108 human invasive ductal carcinoma (IDC) tissues by immunohistochemistry. CRKL protein was upregulated in the cancer tissues compared with adjacent normal mammary glands. Overexpression of CRKL was found in 40 of 108 (37.03 %) breast cancer samples and correlated with advanced p-tumor-node-metastasis stage (p = 0.002), nodal metastasis (p = 0.0323), and tumor size (p = 0.0075). In addition, overexpression of CRKL in the MDA-MB-435 cell line promoted cell proliferation, and small interfering RNA knockdown of CRKL in the MDA-MB-453 cell line inhibited proliferation. Further analysis of cell cycle-related molecules showed that CRKL induced cyclin D1 and phosphorylated extracellular signal-regulated kinase expression. In conclusion, this study demonstrated that overexpression of CRKL correlated with progression and malignant proliferation of human breast cancers.}, } @article {pmid23684711, year = {2013}, author = {Rebollo-Aguirre, AC and Gallego-Peinado, M and Sánchez-Sánchez, R and Pastor-Pons, E and García-García, J and Chamorro-Santos, CE and Menjón-Beltrán, S}, title = {Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with operable breast cancer and positive axillary nodes at initial diagnosis.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {32}, number = {4}, pages = {240-245}, doi = {10.1016/j.remn.2013.03.006}, pmid = {23684711}, issn = {2253-8070}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Prospective Studies ; *Sentinel Lymph Node Biopsy ; }, abstract = {AIM: To evaluate the utility of the sentinel lymph node biopsy (SLNB) in patients with operable breast cancer and positive axillary nodes at initial diagnosis treated with neoadjuvant chemotherapy (NAC).

MATERIAL AND METHODS: A prospective study was performed from January 2008 to December 2012 in 52 women, mean age 50.7 years, with infiltrating breast carcinoma T1-3, N1, M0 (1 bilateral, 7 multifocal) treated with epirubicin/cyclophosphamide, docetaxel and trastuzumab in Her2/neu-positive patients. Axillary evaluation included physical examination, axillary ultrasound, and ultrasound-guided core needle biopsy of any suspicious lymph node. The day before surgery, 74-111 MBq of (99m)Tc-albumin nanocolloid was injected periareolarly. All patients underwent breast surgery, with SLNB and complete axillary lymph node dissection (ALND). The SLNs were examined by frozen sections, hematoxylin-eosin staining, immunohistochemical analysis or one-step nucleic acid amplification assay (OSNA).

RESULTS: Mean tumor size: 3.5 cm. Histologic type: 81.1% invasive ductal carcinoma. Complete response of primary tumor was clinical 43.4%, pathological 41.5%. All patients were clinically node-negative after NAC. Pathological complete response of axillary node was 42.2%. SLN identification rate was 84.9%. Axilla was positive in the pathology study in 6 of 8 patients without nanocolloid migration. SLN accurately represented the axillary status in 95.5%. False negative rate was 8.3%. SLN was the only positive node in 68.2% of patients. Mean number of SLN removed was 1.9 and of nodes resected from the ALND 13.2.

CONCLUSION: SLN biopsy after NAC is a feasible and accurate tool in patients with operable breast cancer T1-3, N1 and clinically node-negative after therapy.}, } @article {pmid23675678, year = {2013}, author = {Efrat, A}, title = {The politics of combating the organ trade: lessons from the Israeli and Pakistani experience.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {13}, number = {7}, pages = {1650-1654}, doi = {10.1111/ajt.12254}, pmid = {23675678}, issn = {1600-6143}, mesh = {*Commerce ; *Government Regulation ; Humans ; International Cooperation ; Israel ; Pakistan ; *Politics ; Tissue Donors/legislation & jurisprudence ; Tissue and Organ Harvesting/*economics/legislation & jurisprudence ; Tissue and Organ Procurement/*economics/legislation & jurisprudence ; }, abstract = {Israel and Pakistan--two major participants in the global organ trade--enacted legislative prohibitions on the trade at roughly the same time. The article highlights three influences that brought about this change of policy in both countries: advocacy by local physicians coupled with media coverage and reinforced by the international medical community. The analysis also explains why the two countries have differed with respect to the enforcement of the organ-trade prohibition. The insights from the Israeli and Pakistani cases will be of use for the transplant community's efforts against organ trafficking.}, } @article {pmid23667369, year = {2013}, author = {Hwangbo, W and Lee, JH and Ahn, S and Kim, S and Park, KH and Kim, CH and Kim, I}, title = {EGFR Gene Amplification and Protein Expression in Invasive Ductal Carcinoma of the Breast.}, journal = {Korean journal of pathology}, volume = {47}, number = {2}, pages = {107-115}, pmid = {23667369}, issn = {1738-1843}, abstract = {BACKGROUND: The epidermal growth factor receptor (EGFR) is a surrogate marker for basal-like breast cancer. A recent study suggested that EGFR may be used as a target for breast cancer treatment.

METHODS: A total of 706 invasive ductal carcinomas (IDC) of the breast were immunophenotyped, and 82 cases with EGFR protein expression were studied for EGFR gene amplification.

RESULTS: EGFR protein was expressed in 121 of 706 IDCs (17.1%); 5.9% were of luminal type, 25.3% of epidermal growth factor receptor 2 (HER-2) type, and 79.3% of basal-like tumors. EGFR gene amplification and high polysomy (fluorescent in situ hybridization [FISH]-positive) were found in 18 of 82 cases (22.0%); 41.2% of the HER-2(+), EGFR(+), cytokeratin 5/6(-) (CK5/6(-)) group, 11.2% of the HER-2(-), EGFR(+), CK5/6(-) group, and 19.1% of the HER-2(-), EGFR(+), CK5/6(+) group. FISH-positive cases were detected in 8.3% of the EGFR protein 1(+) expression cases, 15.9% of 2(+) expression cases, and 38.5% of 3(+) expression cases. In group 2, the tumors had a high Ki-67 labeling (>60%), but the patients showed better disease-free survival than those with tumors that co-expressed HER-2 or CK5/6.

CONCLUSIONS: EGFR-directed therapy can be considered in breast cancer patients with EGFR protein overexpression and gene amplification, and its therapeutic implication should be determined in HER-2 type breast cancer patients.}, } @article {pmid23667202, year = {2013}, author = {de Bruin, MA and Ford, JM and Kurian, AW}, title = {A young woman with bilateral breast cancer: identifying a genetic cause and implications for management.}, journal = {Journal of the National Comprehensive Cancer Network : JNCCN}, volume = {11}, number = {5}, pages = {512-517}, doi = {10.6004/jnccn.2013.0068}, pmid = {23667202}, issn = {1540-1413}, mesh = {Adult ; Biopsy, Large-Core Needle ; Breast Neoplasms/*diagnosis/*etiology/therapy ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genes, p53 ; Humans ; Li-Fraumeni Syndrome/*complications/diagnosis/*genetics ; Mammography ; Mastectomy, Modified Radical ; Neoplasm Staging ; Risk Factors ; }, abstract = {Breast cancer is a common manifestation of an underlying genetic susceptibility to cancer, and 5% to 10% of all breast cancers are associated with a germline mutation in a known risk allele. Detection of mutations has implications for targeted screening and prevention strategies for probands, and for genetic counseling and testing of their family members. This report presents a case involving a 35-year-old woman with no family history of breast or ovarian cancer who presented with a palpable right breast lump. Imaging revealed multiple bilateral breast masses and right axillary adenopathy, and core needle biopsies showed invasive ductal carcinoma in both the right and left breast. This report discusses the appropriate genetics evaluation for a patient with bilateral breast cancer at a young age, including testing for mutations in BRCA1 and BRCA2, followed, if negative, by consideration of testing for mutations in TP53 (Li-Fraumeni syndrome). Given the specialized counseling and testing needs of patients with Li-Fraumeni syndrome, and the implications for targeted screening strategies if a mutation is found, referral to a cancer genetics expert is strongly recommended.}, } @article {pmid23658717, year = {2013}, author = {Guest, JL and Weintrob, AC and Rimland, D and Rentsch, C and Bradley, WP and Agan, BK and Marconi, VC and , }, title = {A comparison of HAART outcomes between the US military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS).}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e62273}, pmid = {23658717}, issn = {1932-6203}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; Y01 AI005072/AI/NIAID NIH HHS/United States ; Y1-AI-5072/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Cohort Studies ; Disease-Free Survival ; Female ; HIV Infections/*drug therapy/immunology/mortality ; HIV-1/*immunology ; Humans ; Male ; Observational Studies as Topic ; Proportional Hazards Models ; Treatment Outcome ; Veterans ; Veterans Health ; Viral Load ; }, abstract = {INTRODUCTION: The Department of Defense (DoD) and the Department of Veterans Affairs (VA) provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence.

METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS) and 1199 patients from the US Military HIV Natural History Study (NHS). Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event.

RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only) and 26.8% to 4.1% (combined mortality or AIDS) when controlling for clinical and demographic variables.

CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics.}, } @article {pmid23658133, year = {2013}, author = {Kim, JH and Baek, TH and Yim, HS and Kim, KH and Jeong, SH and Kang, HB and Oh, SS and Lee, HG and Kim, JW and Kim, KD}, title = {Collagen triple helix repeat containing-1 (CTHRC1) expression in invasive ductal carcinoma of the breast: the impact on prognosis and correlation to clinicopathologic features.}, journal = {Pathology oncology research : POR}, volume = {19}, number = {4}, pages = {731-737}, pmid = {23658133}, issn = {1532-2807}, mesh = {Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Extracellular Matrix Proteins/*biosynthesis/genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; }, abstract = {CTHRC1 has been known as a regulator of collagen expression and cell migration. The aim of this research was to clarify the clinicopathologic significance of CTHRC1 expression in human breast cancer. 22 cases of breast cancer tissues, randomly selected from clinically diagnosed patients, showed a significant increase of CTHRC1 mRNA expression compared to the normal tissue from the same patients using RT-PCR and real-time PCR. Additionally we investigated breast cancers from 189 patients by immunohistochemistry (IHC). A high level of CTHRC1 expression was observed in 111 (58.7 %) out of 189 breast cancer patients and the expression was significantly correlated with histologic grade (P = 0.026), nodal status (P < 0.001), and TNM pathologic stage (P = 0.002). High CTHRC1 expression was associated with a shorter recurrence free survival (P = 0.008). Taken together, the results showed that CTHRC1 over-expression was significantly associated with clinicopathological factors of poor prognosis in invasive ductal carcinoma. CTHRC1 could be used as a supplementary prognostic biomarker and a potential therapeutic target in breast cancer.}, } @article {pmid23652305, year = {2013}, author = {van Hoesel, AQ and Sato, Y and Elashoff, DA and Turner, RR and Giuliano, AE and Shamonki, JM and Kuppen, PJ and van de Velde, CJ and Hoon, DS}, title = {Assessment of DNA methylation status in early stages of breast cancer development.}, journal = {British journal of cancer}, volume = {108}, number = {10}, pages = {2033-2038}, pmid = {23652305}, issn = {1532-1827}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/genetics/pathology ; *DNA Methylation ; Disease Progression ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Laser Capture Microdissection ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*genetics/pathology ; Time Factors ; }, abstract = {BACKGROUND: Molecular pathways determining the malignant potential of premalignant breast lesions remain unknown. In this study, alterations in DNA methylation levels were monitored during benign, premalignant and malignant stages of ductal breast cancer development.

METHODS: To study epigenetic events during breast cancer development, four genomic biomarkers (Methylated-IN-Tumour (MINT)17, MINT31, RARβ2 and RASSF1A) shown to represent DNA hypermethylation in tumours were selected. Laser capture microdissection was employed to isolate DNA from breast lesions, including normal breast epithelia (n=52), ductal hyperplasia (n=23), atypical ductal hyperplasia (n=31), ductal carcinoma in situ (DCIS, n=95) and AJCC stage I invasive ductal carcinoma (IDC, n=34). Methylation Index (MI) for each biomarker was calculated based on methylated and unmethylated copy numbers measured by Absolute Quantitative Assessment Of Methylated Alleles (AQAMA). Trends in MI by developmental stage were analysed.

RESULTS: Methylation levels increased significantly during the progressive stages of breast cancer development; P-values are 0.0012, 0.0003, 0.012, <0.0001 and <0.0001 for MINT17, MINT31, RARβ2, RASSF1A and combined biomarkers, respectively. In both DCIS and IDC, hypermethylation was associated with unfavourable characteristics.

CONCLUSION: DNA hypermethylation of selected biomarkers occurs early in breast cancer development, and may present a predictor of malignant potential.}, } @article {pmid23651947, year = {2013}, author = {Thakur, ML and Zhang, K and Berger, A and Cavanaugh, B and Kim, S and Channappa, C and Frangos, AJ and Wickstrom, E and Intenzo, CM}, title = {VPAC1 receptors for imaging breast cancer: a feasibility study.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {54}, number = {7}, pages = {1019-1025}, pmid = {23651947}, issn = {1535-5667}, support = {R01 CA109231/CA/NCI NIH HHS/United States ; R01 CA157372/CA/NCI NIH HHS/United States ; CA 109231/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnostic imaging/*metabolism ; Copper Radioisotopes/pharmacokinetics ; Feasibility Studies ; Female ; Humans ; Middle Aged ; Molecular Imaging/methods ; Pituitary Adenylate Cyclase-Activating Polypeptide/*pharmacokinetics ; Radionuclide Imaging ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Vasoactive Intestinal Polypeptide, Type I/*metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {UNLABELLED: VPAC1 encodes G-protein-coupled receptors expressed on all breast cancer (BC) cells at the onset of the disease, but not on benign lesions. Our extensive preclinical studies have shown that (64)Cu-TP3805 has a high affinity for VPAC1, is stable in vivo, and has the ability to distinguish spontaneously grown malignant BC masses from benign lesions. Our long-term goal is to develop (64)Cu-TP3805 as an agent to perform in vivo histology, to distinguish malignant lesions from benign masses noninvasively and thereby avoid patient morbidity and the excess economic costs of benign biopsies.

METHODS: (18)F-FDG obtained commercially served as a control. (64)Cu-TP3805 was prepared using a sterile kit containing 20 μg of TP3805. Radiochemical purity and sterility were examined. Nineteen consenting women with histologically proven BC were given 370 MBq of (18)F-FDG. One hour later, 6 of these patients were imaged with PET/CT and 13 with positron emission mammography (PEM). Two to 7 d later, 6 PET/CT patients received 111 MBq (± 10%) (n = 2), 127 MBq (± 10%) (n = 2), or 148 MBq (± 10%) (n = 2) of (64)Cu-TP3805 and were imaged 2 and 4 h later. Thirteen PEM patients received 148 MBq (± 10%) of (64)Cu-TP3805 and were imaged 15 min, 1 h, 2 h, and 4 h later. Standardized uptake value (SUV) was calculated for PET/CT patients, and PUV/BGV (PEM uptake value/background value) was calculated for PEM patients. Tumor volume was also calculated.

RESULTS: The radiochemical purity of (64)Cu-TP3805 was 97% ± 2%, and specific activity was 44.4 GBq (1.2 Ci)/μmol. In 19 patients, a total of 24 lesions were imaged (15 invasive ductal carcinoma, 1 high-grade mammary carcinoma, 3 lobular carcinoma, 1 invasive papilloma, and 4 sentinel lymph nodes). All lesions were unequivocally detected by (64)Cu-TP3805 and by (18)F-FDG. The average tumor volume as determined by PET/CT with (64)Cu-TP3805 was 90.6% ± 16.1% of that with (18)F-FDG PET/CT, and the average SUV was 92% ± 26.4% of that with (18)F-FDG. For PEM, the tumor volume with (64)Cu-TP3805 was 113% ± 37% of that with (18)F-FDG and the PUV/BGV ratio was 97.7% ± 24.5% of that with (18)F-FDG.

CONCLUSION: (64)Cu-TP3805 is worthy of further investigation in patients requiring biopsy of suggestive imaging findings, to further evaluate its ability to distinguish malignant lesions from benign masses noninvasively.}, } @article {pmid23648645, year = {2013}, author = {Alvarez, B and Poderoso, T and Alonso, F and Ezquerra, A and Domínguez, J and Revilla, C}, title = {Antigen targeting to APC: from mice to veterinary species.}, journal = {Developmental and comparative immunology}, volume = {41}, number = {2}, pages = {153-163}, doi = {10.1016/j.dci.2013.04.021}, pmid = {23648645}, issn = {1879-0089}, mesh = {Adaptive Immunity/*immunology ; Animals ; Antigen-Presenting Cells/*immunology/metabolism ; Antigens/*immunology ; Cattle ; Mice ; Receptors, Cell Surface/*immunology/metabolism ; Sheep ; Species Specificity ; Swine ; }, abstract = {Antigen delivery to receptors expressed on antigen presenting cells (APC) has shown to improve immunogenicity of vaccines in mice. An enhancement of cytotoxic T lymphocyte (CTL), helper T cell or humoral responses was obtained depending on the type of APC and the surface molecule targeted. Although this strategy is being also evaluated in livestock animals with promising results, some discrepancies have been found between species and pathogens. The genetic diversity of livestock animals, the different pattern of expression of some receptors among species, the use of different markers to characterize APC in large animals and sometimes the lack of reagents make difficult to compare results obtained in different species. In this review, we summarize the data available regarding antigen targeting to APC receptors in cattle, sheep and pig and discuss the results found in these animals in the context of what has been obtained in mice.}, } @article {pmid23640233, year = {2013}, author = {Dobbs, NB and Latifi, HR}, title = {Diffuse FDG uptake due to fat necrosis following transverse rectus abdominus myocutaneous (TRAM) flap reconstruction.}, journal = {Clinical nuclear medicine}, volume = {38}, number = {8}, pages = {652-654}, doi = {10.1097/RLU.0b013e31828e9948}, pmid = {23640233}, issn = {1536-0229}, mesh = {Biological Transport ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/surgery ; Fat Necrosis/diagnostic imaging/*etiology/*metabolism ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Mammaplasty/*adverse effects ; Middle Aged ; Postoperative Complications/diagnostic imaging/*etiology/*metabolism ; Radiography ; Radionuclide Imaging ; Rectus Abdominis/*surgery ; }, abstract = {We report a case of a 57-year-old female patient with right breast invasive ductal carcinoma. Bilateral mastectomy and TRAM flap reconstructions were performed. Postoperatively, a palpable focus was identified within the left breast. PET/CT showed hypermetabolism throughout the reconstructed left breast, correlating with mixed fat attenuation and inflammatory soft tissue. MRI showed extensive fat necrosis/oil cyst formation in the left breast. As a TRAM flap reconstruction with fat-rich tissue can be damaged intraoperatively due to surgical manipulation, abnormal FDG uptake in this setting is more likely related to fat necrosis than recurrent tumor.}, } @article {pmid23640121, year = {2014}, author = {Liu, D and Xie, G and Chen, M}, title = {Clinicopathologic characteristics and survival of male breast cancer.}, journal = {International journal of clinical oncology}, volume = {19}, number = {2}, pages = {280-287}, pmid = {23640121}, issn = {1437-7772}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/chemistry/mortality/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {BACKGROUNDS: Male breast cancer (MBC) is a rare disease and accounts for <1 % of all breast cancers.

METHODS: We retrospectively analyzed clinicopathologic characteristics and prognosis of MBC patients who were diagnosed in our hospital between March 2002 and March 2012.

RESULTS: The median age of diagnosis of MBC was 62 years, which was 9 years older than female breast cancer (FBC) patients. The highest proportion of MBC patients was in the 50-59-year age group. The percentage of invasive ductal carcinoma in MBC was much higher than in FBC (P = 0.000). The positive rate of estrogen receptors in MBC patients (87.9 %) was significantly higher than in FBC patients (P = 0.048), whereas HER-2 was positive in 17.2 % of MBC patients, which was significantly lower than in FBC patients (P = 0.001). There was a consistent significant difference in luminal subtypes of FBC and MBC patients (P = 0.000). The overall survival rates of MBC were significantly higher than FBC (P = 0.004). HER-2-positive patients had a statistically worse prognosis than HER-2-negative patients (P = 0.040). Lymph node metastasis and larger tumor size were also associated with poorer prognosis (P = 0.056 and P = 0.088). The level of hormones was examined in 7 patients, and abnormal hormone levels were detected in 4.

CONCLUSION: The FBC patients were significantly different from the MBC in clinicopathologic and prognostic characteristics. HER-2 positivity was an important factor for prognosis.}, } @article {pmid23639394, year = {2013}, author = {Sharma, S and Goodarzi, M and Wynants, L and Ramon, H and Saeys, W}, title = {Efficient use of pure component and interferent spectra in multivariate calibration.}, journal = {Analytica chimica acta}, volume = {778}, number = {}, pages = {15-23}, doi = {10.1016/j.aca.2013.03.045}, pmid = {23639394}, issn = {1873-4324}, mesh = {Calibration ; Least-Squares Analysis ; *Models, Statistical ; Spectrum Analysis/*standards ; }, abstract = {Partial Least Squares (PLS) is by far the most popular regression method for building multivariate calibration models for spectroscopic data. However, the success of the conventional PLS approach depends on the availability of a 'representative data set' as the model needs to be trained for all expected variation at the prediction stage. When the concentration of the known interferents and their correlation with the analyte of interest change in a fashion which is not covered in the calibration set, the predictive performance of inverse calibration approaches such as conventional PLS can deteriorate. This underscores the need for calibration methods that are capable of building multivariate calibration models which can be robustified against the unexpected variation in the concentrations and the correlations of the known interferents in the test set. Several methods incorporating 'a priori' information such as pure component spectra of the analyte of interest and/or the known interferents have been proposed to build more robust calibration models. In the present study, four such calibration techniques have been benchmarked on two data sets with respect to their predictive ability and robustness: Net Analyte Preprocessing (NAP), Improved Direct Calibration (IDC), Science Based Calibration (SBC) and Augmented Classical Least Squares (ACLS) Calibration. For both data sets, the alternative calibration techniques were found to give good prediction performance even when the interferent structure in the test set was different from the one in the calibration set. The best results were obtained by the ACLS model incorporating both the pure component spectra of the analyte of interest and the interferents, resulting in a reduction of the RMSEP by a factor 3 compared to conventional PLS for the situation when the test set had a different interferent structure than the one in the calibration set.}, } @article {pmid23634406, year = {2013}, author = {Sangma, MB and Panda, K and Dasiah, S}, title = {A clinico-pathological study on benign breast diseases.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {7}, number = {3}, pages = {503-506}, pmid = {23634406}, issn = {2249-782X}, abstract = {BACKGROUND: To study the patterns of clinically benign breast disease in females and to co-relate them with the pathological findings.

METHODS: One hundred females who attended the Surgery Outpatients Department in Indira Gandhi Medical College and Research Institute, Pondicherry, with various forms of benign breast diseases during the period from October 2011 to September 2012, were studied. Early diagnoses by doing a triple assessment like a clinical examination, FNAC or a core needle biopsy and imaging methods like ultrasonography or mammography, were made within 72 hrs from the first consultation. The clinical diagnoses were compared with the cytological or histological findings wherever possible and their accuracies were evaluated.

RESULTS: Out of the 100 female patients who were studied, 87 patients who presented with breast lumps and fibroadenoma, accounted for 48% of the cases, which was the highest number of patients. Fibrocystic changes and breast abscesses came next with 18% and 12% cases respectively. We detected 3 cases of proliferative disease with atypia and one case with florid hyperplasia, which had high and low risk factors respectively, for developing invasive carcinoma. The oldest lady of the group who was clinically diagnosed to have benign disease, was detected to have invasive ductal carcinoma. They were treated in our hospital and were advised follow up.

CONCLUSION: Benign breast diseases are common in female patients and fibroadenoma is the commonest of them all. Triple assessment provided a quick diagnosis and it alleviated unnecessary anxiety from the patients about breast cancer. The clinical diagnosis of a breast lump, as confirmed by cytology and histology, was accurate in 91.95 % of the cases.}, } @article {pmid23630659, year = {2013}, author = {Diao, X and Chen, Y and Pang, Y}, title = {Automated breast volume scanning: a case demonstration of a breast invasive ductal carcinoma.}, journal = {Quantitative imaging in medicine and surgery}, volume = {3}, number = {2}, pages = {121-125}, doi = {10.3978/j.issn.2223-4292.2013.02.04}, pmid = {23630659}, issn = {2223-4292}, } @article {pmid23630555, year = {2013}, author = {Popiela, TJ and Kibil, W and Herman-Sucharska, I and Urbanik, A}, title = {The use of magnetic resonance mammography in women at increased risk for developing breast cancer.}, journal = {Wideochirurgia i inne techniki maloinwazyjne = Videosurgery and other miniinvasive techniques}, volume = {8}, number = {1}, pages = {55-62}, pmid = {23630555}, issn = {1895-4588}, abstract = {INTRODUCTION: The use of conventional imaging techniques, namely mammography (MMG) and ultrasound (US), for breast cancer (BC) detection in women at high risk for the disease does not bring optimal results in many cases.

AIM: The present study evaluated the effectiveness of magnetic resonance (MR) mammography (MRM) in cases where US and MMG failed to detect suspected breast lesions.

MATERIAL AND METHODS: The study group consisted of 379 women who had had no breast pathologies detected by US and MMG. This group was then divided into 4 groups according to the relative risk of breast cancer development. All the women underwent MRM, and any breast pathology detected by MRM was then verified by open surgical biopsy (OSB).

RESULTS: Based on the MRM findings, 37 women with breast pathologies were identified. All detected pathologies were then classified into one of the BIRADS (Breast Imaging Reporting and Data System) categories. Of these, 33 patients underwent open surgical biopsy. There were a total of 17 benign and 16 malignant breast pathologies that were not visualized by US and MMG. The types of malignancies found, in order of their frequency, were as follows: invasive ductal carcinoma (11 cases), ductal carcinoma in situ (2 cases), invasive lobular carcinoma (2 cases), and lobular carcinoma in situ (1 case). An analysis of MRM effectiveness in detecting BC showed 93.7% sensitivity and 64.71% specificity.

CONCLUSIONS: All women with a 20% or greater lifetime risk of developing BC should undergo annual MRM as a diagnostic adjunct to US and MMG.}, } @article {pmid23630538, year = {2013}, author = {Stec, AO and Bhaskar, PB and Bolon, YT and Nolan, R and Shoemaker, RC and Vance, CP and Stupar, RM}, title = {Genomic heterogeneity and structural variation in soybean near isogenic lines.}, journal = {Frontiers in plant science}, volume = {4}, number = {}, pages = {104}, pmid = {23630538}, issn = {1664-462X}, abstract = {Near isogenic lines (NILs) are a critical genetic resource for the soybean research community. The ability to identify and characterize the genes driving the phenotypic differences between NILs is limited by the degree to which differential genetic introgressions can be resolved. Furthermore, the genetic heterogeneity extant among NIL sub-lines is an unaddressed research topic that might have implications for how genomic and phenotypic data from NILs are utilized. In this study, a recently developed high-resolution comparative genomic hybridization (CGH) platform was used to investigate the structure and diversity of genetic introgressions in two classical soybean NIL populations, respectively varying in protein content and iron deficiency chlorosis (IDC) susceptibility. There were three objectives: assess the capacity for CGH to resolve genomic introgressions, identify introgressions that are heterogeneous among NIL sub-lines, and associate heterogeneous introgressions with susceptibility to IDC. Using the CGH approach, introgression boundaries were refined and previously unknown introgressions were revealed. Furthermore, heterogeneous introgressions were identified within seven sub-lines of the IDC NIL "IsoClark." This included three distinct introgression haplotypes linked to the major iron susceptible locus on chromosome 03. A phenotypic assessment of the seven sub-lines did not reveal any differences in IDC susceptibility, indicating that the genetic heterogeneity among the lines does not have a significant impact on the primary NIL phenotype.}, } @article {pmid23627779, year = {2013}, author = {Bhunia, S and Ghosh, S and Dey, D and Bisai, A}, title = {DDQ-mediated direct intramolecular-dehydrogenative-coupling (IDC): expeditious approach to the tetracyclic core of ergot alkaloids.}, journal = {Organic letters}, volume = {15}, number = {10}, pages = {2426-2429}, doi = {10.1021/ol400899e}, pmid = {23627779}, issn = {1523-7052}, abstract = {An efficient route to 2-oxindoles bearing an all-carbon quaternary center at the pseudobenzylic position has been developed via a DDQ-mediated Intramolecular-Dehydrogenative-Coupling (IDC). The methodology involves a one-pot C-alkylation of β-N-arylamido esters (7) concomitant with dehydrogenative-coupling in the presence of stoichiometric amount of DDQ. A tentative mechanistic route has been proposed for the oxidative coupling. The methodology provides a two-step entry to the ergoline structure of ergot alkaloids.}, } @article {pmid23623331, year = {2013}, author = {Yoshizawa, S and Kato, TS and Mancini, D and Marboe, CC}, title = {Outcome of patients having heart transplantation for lymphocytic myocarditis.}, journal = {The American journal of cardiology}, volume = {112}, number = {3}, pages = {405-410}, doi = {10.1016/j.amjcard.2013.03.042}, pmid = {23623331}, issn = {1879-1913}, mesh = {Adult ; Biopsy ; Cardiomyopathy, Dilated/mortality/pathology/surgery ; Endocardium/pathology ; Female ; Follow-Up Studies ; Graft Rejection/*mortality/pathology ; *Heart Transplantation/pathology ; Hospitals, University ; Humans ; Lymphocytosis/mortality/pathology/*surgery ; Male ; Middle Aged ; Myocardial Ischemia/mortality/pathology/surgery ; Myocarditis/mortality/pathology/*surgery ; Myocardium/pathology ; New York City ; Postoperative Complications/*mortality/pathology ; Prognosis ; Survival Rate ; }, abstract = {Heart transplantation (HT) for myocarditis has been controversial because of earlier reports of a poor prognosis after the procedure. We sought to determine whether lymphocytic myocarditis (LM) at the time of HT affects cardiac allograft rejection and survival after HT compared with other patients without LM in the current era of HT. We retrospectively reviewed 759 consecutive patients who underwent de novo HT at Columbia University Medical Center between 2000 and 2010 and compared prognosis after HT of the patients with pathologically proven LM in their explanted hearts with that of age- and gender-matched patients with idiopathic dilated cardiomyopathy (IDC group; n = 96) and with ischemic cardiomyopathy (IC group; n = 64). Thirty-two patients (4.2%) had LM in the explanted hearts pathologically. Among the 3 groups, no statistically significant difference was observed in the number of biopsy-diagnosed acute cellular rejection (ACR; International Society for Heart & Lung Transportation grade ≥2R) events during the first year after HT. In contrast, the frequency of biopsy-diagnosed ACR in subsequent years was greater in the LM group (n = 8, 3.8%) than in IC group (n = 3, 0.5%, p = 0.006), although no different from that of patients with IDC. The frequency of antibody-mediated rejection and posttransplant survival did not differ among the 3 groups. In conclusion, patients with pre-HT LM have an increased frequency of late ACR after HT compared with patients with IC. Nevertheless, survival of LM patients after HT is comparable to that of patients transplanted for IDC or IC.}, } @article {pmid23618841, year = {2013}, author = {Holloway, CM and Scollard, DA and Caldwell, CB and Ehrlich, L and Kahn, HJ and Reilly, RM}, title = {Phase I trial of intraoperative detection of tumor margins in patients with HER2-positive carcinoma of the breast following administration of 111In-DTPA-trastuzumab Fab fragments.}, journal = {Nuclear medicine and biology}, volume = {40}, number = {5}, pages = {630-637}, doi = {10.1016/j.nucmedbio.2013.03.005}, pmid = {23618841}, issn = {1872-9614}, mesh = {*Antibodies, Monoclonal, Humanized/administration & dosage/chemistry/pharmacokinetics ; Breast Neoplasms/*diagnosis/diagnostic imaging/*pathology/surgery ; Feasibility Studies ; Female ; Humans ; Immunoglobulin Fab Fragments/*chemistry ; *Indium Radioisotopes ; Intraoperative Period ; Middle Aged ; Pentetic Acid/*chemistry ; Radiometry ; Radiopharmaceuticals/administration & dosage/chemistry/pharmacokinetics ; Receptor, ErbB-2/*metabolism ; Safety ; Tomography, Emission-Computed, Single-Photon ; Trastuzumab ; }, abstract = {INTRODUCTION: Our aim was to conduct a Phase I clinical trial to determine the feasibility of intraoperative detection of tumor margins in HER2 positive breast carcinoma using a hand-held γ-probe following administration of (111)In-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence.

METHODS: Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74MBq (0.5mg) of (111)In-DTPA-trastuzumab Fab fragments and counts in the tumor, surgical cavity wall and en face margins were measured intraoperatively at 72h post-injection using the Navigator or C-Trak γ-probes. Margins were evaluated histologically. Quantitative whole body planar imaging was performed to estimate radiation absorbed doses using OLINDA/EXM software. SPECT imaging of the thorax was performed to evaluate tumor uptake. The pharmacokinetics of elimination from the blood and plasma were determined over 72h.

RESULTS: There were no acute adverse reactions from (111)In-DTPA-trastuzumab Fab fragments and no changes in hematological or biochemical indices were found over a 3month period. (111)In-DTPA-trastuzumab Fab fragments exhibited a biphasic elimination from the blood and plasma with t1/2α=11.9h and 7.5h, respectively, and t1/2β=26.6 and 20.7h, respectively. The radiopharmaceutical accumulated in the liver, spleen and kidneys. SPECT imaging did not reveal tumor in any patient. The mean effective dose was 0.146mSv/MBq (10.8mSv for 74MBq). Counts in excised tumors were low but were higher than in margins. Margins in two patients harboured tumor but this was not correlated with counts obtained using the γ-probes. Surgical cavity counts were high and likely due to detection of γ-photons outside the surgical field.

CONCLUSION: We conclude that it was not feasible, at least at the administered amount of radioactivity used in this study, to reliably detect the margins of disease in patients with in situ or invasive ductal carcinoma intraoperatively using a hand-held γ-probe and (111)In-DTPA-trastuzumab Fab fragments due to low uptake in the tumor and involved margins.}, } @article {pmid23614916, year = {2013}, author = {Horiguchi, H and Yamagata, S and Rong Qian, Z and Kagawa, S and Sakashita, N}, title = {Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis.}, journal = {The journal of medical investigation : JMI}, volume = {60}, number = {1-2}, pages = {91-96}, doi = {10.2152/jmi.60.91}, pmid = {23614916}, issn = {1349-6867}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Thrombospondin 1/analysis/*physiology ; }, abstract = {Desmoplastic (scirrhous) invasion and lymph node metastasis are critical for the treatment and prognosis of invasive ductal carcinoma of the breast. Despite being an anti-angiogenic therapeutic candidate, Thrombospondin-1 (TSP-1) promotes invasion and metastasis of some carcinomas. To clarify the effect of TSP-1 on invasion and metastasis, we obtained 101 invasive ductal carcinomas of the breast with axillary lymph node resection. All tumors were histologically divided into two categories, carcinomas with, and those with non- /minimal desmoplastic component. Immunohistochemistry for TSP-1 was performed on all primary tumors and axillary lymph nodes with tumor metastasis. Fifty-four (53.5%) of 101 tumors were recognized as positive for TSP-1 in the cytoplasm of tumor cells. Histological study showed that significantly more cancers with desmoplastic components (46/69, 66.7%) manifested TSP-1 expression than did cancers with no- or minimal (less than 20%) desmoplasia (8/32, 25.0%; p<0.001). Axillary lymph node metastasis was significantly higher in TSP-1-positive- (28/54, 51.9%) than TSP-1-negative cancers (11/47, 23.4%; p<0.005). The present study indicates that tumor cells in the desmoplastic component strongly expressed TSP-1 in invasive ductal carcinoma of the breast and TSP-1 participates in invasion of these tumors. Our findings also suggest that TSP-1 promotes lymph node metastasis and TSP-1 potentially could be a predictive marker for metastasis.}, } @article {pmid23609359, year = {2013}, author = {Zhang, BH and Liu, J and Zhou, QX and Zuo, D and Wang, Y}, title = {Analysis of differentially expressed genes in ductal carcinoma with DNA microarray.}, journal = {European review for medical and pharmacological sciences}, volume = {17}, number = {6}, pages = {758-766}, pmid = {23609359}, issn = {1128-3602}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis/methods ; Transcriptome ; }, abstract = {AIM: The aim of this study is to investigate the dysregulated biological functions that play important role in the occurrence and development of breast invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: We downloaded the gene expression profile data from gene expression omnibus (GEO) database, including 42 disease samples and 143 adjacent histological normal samples. Significance analysis of microarrays (SAM) was employed to identify differentially expressed genes (DEGs) between the normal and disease samples. Gene ontology (GO) function enrichment analysis was based on Software DAVID, followed by KEGG pathway enrichment analysis. TRANSFAC database and HPRD database were employed to construct the transcriptional regulatory network (Tnet) and protein-protein interaction (PPI) network, respectively.

RESULTS: We got a total of 1769 genes significantly differentially expressed, including 907 up-regulated genes and 862 down-regulated genes. Functional analysis revealed that hormone-responsive genes are related with the occurrence of cancer. Then, we successfully constructed IDC-specific Tnet and PPI network with DEGs response to hormone and obtained some hub genes, such as FOS and PIK3R1, in these networks. Besides, ten modules were found in these networks.

CONCLUSIONS: Hormone-responsive genes and modules may play an important role in the occurrence and development of IDC. Based on the findings above, we got a preliminary understand of the occurrence, development and metastasis of the IDC and possibly provided effective information on the biogenesis of IDC.}, } @article {pmid23607710, year = {2013}, author = {Cao, AY and He, M and Huang, L and Shao, ZM and Di, GH}, title = {Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {91}, pmid = {23607710}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*mortality/secondary/therapy ; Carcinoma, Medullary/epidemiology/*mortality/secondary/therapy ; China/epidemiology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*mortality/pathology/therapy ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database.

METHODS: A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups.

RESULTS: There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival.

CONCLUSIONS: MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.}, } @article {pmid23605249, year = {2013}, author = {Ren, Q and Zhang, L and Ruoff, R and Ha, S and Wang, J and Jain, S and Reuter, V and Gerald, W and Giri, DD and Melamed, J and Garabedian, MJ and Lee, P and Logan, SK}, title = {Expression of androgen receptor and its phosphorylated forms in breast cancer progression.}, journal = {Cancer}, volume = {119}, number = {14}, pages = {2532-2540}, pmid = {23605249}, issn = {1097-0142}, support = {R01 CA112226/CA/NCI NIH HHS/United States ; UL1 RR029893/RR/NCRR NIH HHS/United States ; 1UL1RR029893/RR/NCRR NIH HHS/United States ; R01CA112226/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phosphorylation ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Androgen/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Up-Regulation ; }, abstract = {BACKGROUND: Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser[P]-213) and Ser-650 (AR-Ser[P]-650), in breast cancer and evaluated their association with clinicopathological parameters.

METHODS: Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore.

RESULTS: Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (P = .0014) and 1.7-fold (P = .05), respectively, compared with benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both P < .0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, P = .05), ER-negative (2.6-fold, P = .001), and invasive ductal carcinoma (6.8-fold, P = .04). AR-Ser(P)-650 expression was downregulated in lymph node-positive breast cancers (1.4-fold, P = .02) but was upregulated in invasive ductal carcinomas (3.2-fold, P < .0001) and metastases (1.5-fold, P = .003). Moreover, in ER-negative breast cancers, nuclear AR-Ser(P)-650 was decreased (1.4-fold, P = .005), and cytoplasmic AR-Ser(P)-650 was increased (1.4-fold, P = .003).

CONCLUSIONS: AR and its phosphorylation at serines 213 and 650 are differentially expressed in breast cancer tumorigenesis and progression. Phosphorylation of AR at serines 213 and 650 is increased in ER-negative breast cancers, ductal carcinomas, and metastases and may have predictive value in breast cancer prognosis.}, } @article {pmid23600833, year = {2013}, author = {Lloberas, N and Rama, I and Llaudó, I and Torras, J and Cerezo, G and Cassis, L and Franquesa, M and Merino, A and Benitez-Ribas, D and Cruzado, JM and Herrero-Fresneda, I and Bestard, O and Grinyó, JM}, title = {Dendritic cells phenotype fitting under hypoxia or lipopolysaccharide; adenosine 5'-triphosphate-binding cassette transporters far beyond an efflux pump.}, journal = {Clinical and experimental immunology}, volume = {172}, number = {3}, pages = {444-454}, pmid = {23600833}, issn = {1365-2249}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors/metabolism ; ATP-Binding Cassette Transporters/antagonists & inhibitors/*metabolism ; Cell Differentiation ; Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/cytology/drug effects/immunology/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lipopolysaccharides/pharmacology ; Lymphocyte Culture Test, Mixed ; Lymphocyte Subsets/cytology/drug effects/immunology/metabolism ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/antagonists & inhibitors/metabolism ; Phenotype ; }, abstract = {This study examines adenosine 5'-triphosphate-binding cassette (ABC) transporters as a potential therapeutic target in dendritic cell (DC) modulation under hypoxia and lipopolysaccharide (LPS). Functional capacity of dendritic cells (DCs) (mixed lymphocyte reaction: MLR) and maturation of iDCs were evaluated in the presence or absence of specific ABC-transporter inhibitors. Monocyte-derived DCs were cultured in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). Their maturation under hypoxia or LPS conditions was evaluated by assessing the expression of maturation phenotypes using flow cytometry. The effect of ABC transporters on DC maturation was determined using specific inhibitors for multi-drug resistance (MDR1) and multi-drug resistance proteins (MRPs). Depending on their maturation status to elicit T cell alloresponses, the functional capacity of DCs was studied by MLR. Mature DCs showed higher P-glycoprotein (Pgp) expression with confocal microscopy. Up-regulation of maturation markers was observed in hypoxia and LPS-DC, defining two different DC subpopulation profiles, plasmacytoid versus conventional-like, respectively, and different cytokine release T helper type 2 (Th2) versus Th1, depending on the stimuli. Furthermore, hypoxia-DCs induced more B lymphocyte proliferation than control-iDC (56% versus 9%), while LPS-DCs induced more CD8-lymphocyte proliferation (67% versus 16%). ABC transporter-inhibitors strongly abrogated DC maturation [half maximal inhibitory concentration (IC50): P-glycoprotein inhibition using valspodar (PSC833) 5 μM, CAS 115104-28-4 (MK571) 50 μM and probenecid 2·5 μM], induced significantly less lymphocyte proliferation and reduced cytokine release compared with stimulated-DCs without inhibitors. We conclude that diverse stimuli, hypoxia or LPS induce different profiles in the maturation and functionality of DC. Pgp appears to play a role in these DC events. Thus, ABC-transporters emerge as potential targets in immunosuppressive therapies interfering with DCs maturation, thereby abrogating innate immune response when it is activated after ischaemia.}, } @article {pmid23600528, year = {2013}, author = {Yang, YL and Fan, Y and Lang, RG and Ding, XM and Zhang, XM and Fu, L}, title = {Invasive ductal carcinoma with osteoclastic giant cells of breast: clinicopathologic characteristics.}, journal = {The breast journal}, volume = {19}, number = {3}, pages = {329-330}, doi = {10.1111/tbj.12109}, pmid = {23600528}, issn = {1524-4741}, mesh = {Breast/pathology ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Giant Cells/*pathology ; Humans ; Middle Aged ; Osteoclasts/*pathology ; }, } @article {pmid23598968, year = {2013}, author = {Vandenbussche, CJ and Khouri, N and Sbaity, E and Tsangaris, TN and Vang, R and Tatsas, A and Cimino-Mathews, A and Argani, P}, title = {Borderline atypical ductal hyperplasia/low-grade ductal carcinoma in situ on breast needle core biopsy should be managed conservatively.}, journal = {The American journal of surgical pathology}, volume = {37}, number = {6}, pages = {913-923}, pmid = {23598968}, issn = {1532-0979}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/*surgery ; Female ; Humans ; Hyperplasia/pathology/surgery ; }, abstract = {The differential diagnosis of low-nuclear grade intraductal epithelial proliferations of the breast includes atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). This distinction can be difficult on core needle biopsy (CNB) but can have significant clinical ramifications. We examined the clinical course of patients diagnosed on CNB with borderline ADH/DCIS lesions [marked ADH (MADH)] at our institution. A total of 74 patients were diagnosed with MADH on CNB and underwent an excisional biopsy (EB). The majority of these CNBs reviewed at outside hospitals had been classified as DCIS. Twenty patients (27%) had benign findings or lobular neoplasia in their EB, 18 (24%) had ADH, 33 (45%) had DCIS, and 3 (4%) had DCIS and invasive ductal carcinoma (IDC). Among the 38 patients who were not diagnosed with DCIS or IDC on EB, no patient underwent further surgery or radiation postoperatively. Thirty-seven of these 38 patients had no recurrences, whereas 1 patient developed a "recurrence" that on our review was likely residual localized MADH. The mean follow-up for these patients was 54 months. Of the 36 patients diagnosed with DCIS or IDC on EB, <20% required mastectomy. On review, MADH involving an intermediate-sized duct on CNB and the amount of residual lesion on imaging was significantly associated with DCIS or IDC on EB. Conversely, MADH involving columnar cell lesions and the presence of calcification on CNB were significantly associated with benign pathology on EB. In conclusion, our study provides preliminary data that justify a conservative approach to borderline ADH/DCIS lesions on CNB: that is, diagnose as MADH and treat by conservative excision.}, } @article {pmid23593567, year = {2013}, author = {Zavyalova, MV and Denisov, EV and Tashireva, LA and Gerashchenko, TS and Litviakov, NV and Skryabin, NA and Vtorushin, SV and Telegina, NS and Slonimskaya, EM and Cherdyntseva, NV and Perelmuter, VM}, title = {Phenotypic drift as a cause for intratumoral morphological heterogeneity of invasive ductal breast carcinoma not otherwise specified.}, journal = {BioResearch open access}, volume = {2}, number = {2}, pages = {148-154}, pmid = {23593567}, issn = {2164-7844}, abstract = {Invasive ductal carcinoma (IDC) not otherwise specified (NOS), the most common type of breast cancer, demonstrates great intratumoral morphological heterogeneity, which encompasses the presence of different types of morphological structures-tubular, trabecular, solid, and alveolar structures and discrete groups of tumor cells, the origins of which remain unclear at present. In this study of 162 IDC NOS patients, we investigated whether the distribution of different types of morphological structures is related to the basic clinicopathological parameters of IDC NOS. Our results showed that in patients with only one type of tumor structure, the presence of any one of the five types was equally probable; however, cases with two types of structures were more likely to contain trabecular structures than the other four types. The development of intratumoral morphological heterogeneity was not associated with menopausal status, tumor size, histological grade, hematogenic metastasis, or recurrence. However, the number of different types of morphological structures was significantly higher in luminal tumors than in triple-negative tumors. An increase in the frequency of lymph node metastasis correlated with the increased number of different types of structures in breast tumors; however, in contrast to premenopausal patients, this association was explained by the presence of alveolar structures in postmenopausal women. In addition, we showed a significant decrease in the numbers of positive lymph nodes in tumors with high numbers of morphological variants. The frequency of lymph node metastases and the number of positive nodes were generally independent features and formed by different mechanisms. Based on the evidence, the term "phenotypic drift" has been designated as the basis for the development of intratumoral morphological heterogeneity of IDC NOS.}, } @article {pmid23589849, year = {2013}, author = {Volinia, S and Croce, CM}, title = {Prognostic microRNA/mRNA signature from the integrated analysis of patients with invasive breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {18}, pages = {7413-7417}, pmid = {23589849}, issn = {1091-6490}, support = {U01 CA152758/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/classification/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Cohort Studies ; DNA Methylation/genetics ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; Genome, Human/genetics ; Humans ; Kaplan-Meier Estimate ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; Prognosis ; RNA, Messenger/genetics/metabolism ; ROC Curve ; Reproducibility of Results ; Risk Factors ; }, abstract = {The optimal management of breast cancer (BC) presents challenges due to the heterogeneous molecular classification of the disease. We performed survival analysis on a cohort of 466 patients with primary invasive ductal carcinoma (IDC), the most frequent type of BC, by integrating mRNA, microRNA (miRNA), and DNA methylation next-generation sequencing data from The Cancer Genome Atlas (TCGA). Expression data from eight other BC cohorts were used for validation. The prognostic value of the resulting miRNA/mRNA signature was compared with that of other prognostic BC signatures. Thirty mRNAs and seven miRNAs were associated with overall survival across different clinical and molecular subclasses of a 466-patient IDC cohort from TCGA. The prognostic RNAs included PIK3CA, one of the two most frequently mutated genes in IDC, and miRNAs such as hsa-miR-328, hsa-miR-484, and hsa-miR-874. The area under the curve of the receiver-operator characteristic for the IDC risk predictor in the TCGA cohort was 0.74 at 60 mo of overall survival (P < 0.001). Most relevant for clinical application, the integrated signature had the highest prognostic value in early stage I and II tumors (receiver-operator characteristic area under the curve = 0.77, P value < 0.001). The genes in the RNA risk predictor had an independent prognostic value compared with the clinical covariates, as shown by multivariate analysis. The integrated RNA signature was successfully validated on eight BC cohorts, comprising a total of 2,399 patients, and it had superior performance for risk stratification with respect to other RNA predictors, including the mRNAs used in MammaPrint and Oncotype DX assays.}, } @article {pmid23589556, year = {2013}, author = {Metzger-Filho, O and Procter, M and de Azambuja, E and Leyland-Jones, B and Gelber, RD and Dowsett, M and Loi, S and Saini, KS and Cameron, D and Untch, M and Smith, I and Gianni, L and Baselga, J and Jackisch, C and Bell, R and Sotiriou, C and Viale, G and Piccart-Gebhart, M}, title = {Magnitude of trastuzumab benefit in patients with HER2-positive, invasive lobular breast carcinoma: results from the HERA trial.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {31}, number = {16}, pages = {1954-1960}, doi = {10.1200/JCO.2012.46.2440}, pmid = {23589556}, issn = {1527-7755}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Adult ; Aged ; Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/pathology ; Carcinoma, Lobular/chemistry/*drug therapy/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Proportional Hazards Models ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; Trastuzumab ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive lobular carcinoma (ILC) enrolled onto the Herceptin Adjuvant (HERA) trial.

PATIENTS AND METHODS: Patients randomly assigned to receive one year of trastuzumab and one year of observation in the HERA trial were included (n = 3,401). Centrally reviewed estrogen receptor (ER), progesterone receptor (PgR), and HER2 copy numbers were used. First site-specific relapse pattern was evaluated for ILC and invasive ductal carcinoma (IDC). The magnitude of trastuzumab benefit was assessed using the Cox proportional hazards model for disease-free survival (DFS) and overall survival (OS).

RESULTS: Median follow-up time was 4 years. A total of 187 ILC and 3,213 IDC patients were included. High Allred scores (6 to 8) were more common in patients with ILC than IDC for both ER (36.9% v 22.7%) and PgR (44.1% v 28.5%). A trend toward decreased HER2 copy number was observed in the ILC group. The ILC and IDC subgroups had similar patterns of first site of disease relapse. DFS hazard ratios (HRs) comparing 1 year of trastuzumab versus observation were 0.63 for ILC (95% CI, 0.34 to 1.15) and 0.77 for IDC (95% CI, 0.67 to 0.89; P for interaction = .49). The OS HRs comparing 1 year of trastuzumab versus observation were 0.60 for ILC (95% CI, 0.27 to 1.31) and 0.86 for IDC (95% CI, 0.71 to 1.06; P for interaction = .29).

CONCLUSION: In this retrospective analysis, there was no suggestion that patients in the ILC cohort experienced a different magnitude of benefit from adjuvant trastuzumab than those in the IDC cohort.}, } @article {pmid23584595, year = {2015}, author = {Ono, M and Tsuda, H and Yunokawa, M and Yonemori, K and Shimizu, C and Tamura, K and Kinoshita, T and Fujiwara, Y}, title = {Prognostic impact of Ki-67 labeling indices with 3 different cutoff values, histological grade, and nuclear grade in hormone-receptor-positive, HER2-negative, node-negative invasive breast cancers.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {22}, number = {2}, pages = {141-152}, doi = {10.1007/s12282-013-0464-4}, pmid = {23584595}, issn = {1880-4233}, mesh = {Asian People ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/genetics/metabolism/*mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Ki-67 Antigen/*analysis/metabolism ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; }, abstract = {BACKGROUND: The criteria for classifying hormone receptor (HR)-positive/HER2-negative breast cancers into low-risk and high-risk subgroups remain undetermined. Supportive data for optimal criteria to identify tumors in the high-risk subgroup are necessary for Japanese patients with HR-positive/HER2-negative breast cancers.

METHODS: Using immunohistochemistry and fluorescence in situ hybridization, we identified 369 consecutive patients with HR-positive/HER2-negative, node-negative invasive breast cancers. We examined the prognostic impact of the Ki-67 labeling index (LI) based on 3 cutoff values, 10, 14, and 20 %, along with that of histological grade (HG) and nuclear grade (NG) by Cox's univariate and multivariate analyses.

RESULTS: The univariate analyses clearly showed that Ki-67 LI with any cutoff value divided the patients into distinct high-risk and low-risk groups, and that HG and NG were also powerful prognostic indicators. High Ki-67 LI with any cutoff value was strongly correlated with HG and NG, and when these parameters were included in the multivariate analyses, the impact of HG/NG was stronger than Ki-67 LIs. When the 10 % cutoff value was adopted, discordance between Ki-67 LI and grades was frequent in papillotubular-type invasive ductal carcinoma, predominantly intraductal carcinoma, and mucinous carcinoma.

CONCLUSIONS: Any of the Ki-67 LI values, regardless of cutoff value, could be applicable for the classification of high-risk and low-risk HR-positive/HER2-negative, node-negative invasive breast cancers. Luminal A/B subtyping according to Ki-67 LI, or HG/NG, in combination with histological type, appeared to be able to create an optimum risk estimation system for patients with HR-positive/HER2-negative, node-negative invasive breast cancers in Japan.}, } @article {pmid23575073, year = {2013}, author = {Rao, C and Shetty, J and Kishan Prasad, HL}, title = {Morphological profile and receptor status in breast carcinoma: an institutional study.}, journal = {Journal of cancer research and therapeutics}, volume = {9}, number = {1}, pages = {44-49}, doi = {10.4103/0973-1482.110358}, pmid = {23575073}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Burden ; }, abstract = {CONTEXT: The data on histological and receptor status in breast cancer in an Indian population is limited as receptor status is not routinely carried out for these patients. In the present study, receptor status was analyzed and it was correlated with morphological prognostic parameters.

OBJECTIVE: To analyze the morphological prognostic parameters and its correlation with receptor status in Indian women.

DESIGN: The sample consisted of 126 specimens of invasive breast cancer received in department of pathology of our institution with teaching hospital attached to it, situated in South Canara district of, Karnataka, South India between year 2009 and 2011.

RESULT: Sixty-seven percent of patients were 50 years or younger. Histological types were invasive ductal carcinoma, not otherwise specified (58.7%), and overall (15.9%) were grade 3. Estrogen receptor was positive in 36.5%, HER/neu was overexpressed in only three cases; 50.0% were "triple" negative (estrogen receptor, progesterone receptor, HER/neu negative). Estrogen receptor (ER) and progesterone receptor (PR) positivity decreased with increase in tumor grade. There was significant association between tumor size and ER positivity.

CONCLUSIONS: Breast carcinoma in our population presents at younger age than Western population. Our results showed very high proportion of triple-negative breast cancers. The tumor size and grade is related to expression of only ER. The findings suggest that women in our population more often have histologically aggressive breast carcinoma at young age, likely to be less susceptible to conventional hormonal and targeted antibody treatment. Detecting and treating this increasing important cause of mortality will be an enormous challenge.}, } @article {pmid23573438, year = {2013}, author = {Arslan, D and Tural, D and Tatlı, AM and Akar, E and Uysal, M and Erdoğan, G}, title = {Isolated uterine metastasis of invasive ductal carcinoma.}, journal = {Case reports in oncological medicine}, volume = {2013}, number = {}, pages = {793418}, pmid = {23573438}, issn = {2090-6706}, abstract = {Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.}, } @article {pmid23564785, year = {2013}, author = {Pula, B and Wojnar, A and Werynska, B and Ambicka, A and Kruczak, A and Witkiewicz, W and Ugorski, M and Podhorska-Okolow, M and Dziegiel, P}, title = {Impact of different tumour stroma assessment methods regarding podoplanin expression on clinical outcome in patients with invasive ductal breast carcinoma.}, journal = {Anticancer research}, volume = {33}, number = {4}, pages = {1447-1455}, pmid = {23564785}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/metabolism/*mortality/pathology ; Female ; Fibroblasts/metabolism/*pathology ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Membrane Glycoproteins/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Stromal Cells/metabolism/*pathology ; Survival Rate ; }, abstract = {BACKGROUND: Podoplanin, a small mucin-type transmembrane protein has been shown in several studies to be expressed in cancer-associated fibroblasts (CAFs) and affect patient outcome.

MATERIALS AND METHODS: We evaluated podoplanin expression in CAFs in a cohort of 257 patients with invasive ductal breast carcinomas (IDCs) using three different assessment scales based on the number of positive cells alone or in combination with the reaction intensity.

RESULTS: Two of the utilized scales yielded prognostic information concerning patients' overall survival (OS), but scores were not independent prognostic factors in the multivariate analysis. On the contrary, two scales based on the combination of cell positivity and reaction intensity had no significant impact on patients' OS, but they were significantly correlated with a greater number of analysed clinicopathological parameters.

CONCLUSION: In summary, podoplanin expression in CAFs may be considered a possible marker of poor prognosis in IDC, however, caution should be taken as the results varied regarding the utilized scales.}, } @article {pmid23561623, year = {2013}, author = {Liang, F and Cao, W and Wang, Y and Li, L and Zhang, G and Wang, Z}, title = {The prognostic value of tumor budding in invasive breast cancer.}, journal = {Pathology, research and practice}, volume = {209}, number = {5}, pages = {269-275}, doi = {10.1016/j.prp.2013.01.009}, pmid = {23561623}, issn = {1618-0631}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Cell Proliferation ; China/epidemiology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Observer Variation ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Reproducibility of Results ; Retrospective Studies ; Survival Rate ; }, abstract = {We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.}, } @article {pmid23560566, year = {2013}, author = {Mikulincer, M and Shaver, PR and Sahdra, BK and Bar-On, N}, title = {Can security-enhancing interventions overcome psychological barriers to responsiveness in couple relationships?.}, journal = {Attachment & human development}, volume = {15}, number = {3}, pages = {246-260}, doi = {10.1080/14616734.2013.782653}, pmid = {23560566}, issn = {1469-2988}, mesh = {Analysis of Variance ; Courtship/*psychology ; Female ; Humans ; *Interpersonal Relations ; Israel ; Male ; *Object Attachment ; Regression Analysis ; *Social Behavior ; Surveys and Questionnaires ; United States ; Young Adult ; }, abstract = {Recent studies have shown that both dispositional and experimentally enhanced attachment security facilitate compassion and altruism. Here we report findings from a laboratory experiment, replicated in two countries (Israel and the United States), testing the hypotheses that (a) increased security (accomplished through subliminal priming) fosters caregiving behavior toward a romantic partner who discloses a personal problem, and (b) this increased security overcomes barriers to responsiveness induced by mental depletion. We gathered data on participants' attachment insecurities, randomly assigned them to one of four mental depletion (yes, no) and priming (security, neutral) conditions, and coded their behavior in an interaction with their romantic partner who was disclosing a personal problem. Dispositional attachment insecurities and manipulated mental depletion adversely affected caregiving, but security priming overrode the detrimental effects of both mental depletion and attachment insecurity in both Israel and the United States.}, } @article {pmid23559354, year = {2013}, author = {Jang, SM and Sim, J and Han, H and Ahn, HI and Kim, H and Yi, K and Jun, YJ and Rehman, A and Chung, MS and Jang, K and Paik, SS}, title = {Clinicopathological significance of CADM4 expression in invasive ductal carcinoma of the breast.}, journal = {Journal of clinical pathology}, volume = {66}, number = {8}, pages = {681-686}, doi = {10.1136/jclinpath-2012-201405}, pmid = {23559354}, issn = {1472-4146}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Down-Regulation ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {AIMS: Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor involved in cell adhesion. Loss or decreased expression of CADM4 has been associated with the development and progression of some cancers. The purpose of this study was to investigate the clinicopathological significance of CADM4 expression in breast cancer.

METHODS: We constructed tissue microarrays to evaluate the immunohistochemical expression of CADM4 in 256 cases of invasive ductal carcinoma (IDC) and 45 cases of ductal carcinoma in situ (DCIS).

RESULTS: CADM4 was expressed in 37 (82.2%) DCIS cases, and in 173 (67.6%) IDC cases. CADM4 expression was higher in DCIS than in IDC (p=0.049). Loss or decrease of CADM4 expression was significantly correlated with higher histological grade (p=0.020), absence of oestrogen receptors (p<0.001), absence of progesterone receptors (p=0.024), and overexpression of c-erbB-2 (p=0.018). In univariable and multivariable Cox regression analyses of all 256 IDC cases, CADM4 expression was not significantly associated with overall and disease-free survival. However, it showed a significant positive association with longer disease-free survival in 187 stages I and II IDC cases (p=0.039, log-rank test).

CONCLUSIONS: Loss or decrease of CADM4 expression seems to play an important role in breast cancer invasiveness, and it is associated with poorer biological parameters. CADM4 can be used as a novel marker predicting risk of recurrence and disease outcomes in stages I and II IDC.}, } @article {pmid23553679, year = {2013}, author = {Blau, GE and Orcun, S and Laínez, JM and Reklaitis, GV and Suvannasankha, A and Fausel, C and Anaissie, EJ}, title = {Validation of a novel approach for dose individualization in pharmacotherapy using gabapentin in a proof of principles study.}, journal = {Pharmacotherapy}, volume = {33}, number = {7}, pages = {727-735}, doi = {10.1002/phar.1267}, pmid = {23553679}, issn = {1875-9114}, mesh = {Amines/*administration & dosage/pharmacokinetics ; Analgesics/*administration & dosage/pharmacokinetics ; Bayes Theorem ; Cyclohexanecarboxylic Acids/*administration & dosage/pharmacokinetics ; Decision Support Techniques ; Dose-Response Relationship, Drug ; Drug Monitoring/*methods ; Gabapentin ; Humans ; Point-of-Care Systems ; Precision Medicine/methods ; Retrospective Studies ; Sensitivity and Specificity ; Time Factors ; gamma-Aminobutyric Acid/*administration & dosage/pharmacokinetics ; }, abstract = {STUDY OBJECTIVE: To demonstrate the premise of individualized dosing charts (IDCs) as a clinical-bedside decision-support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic (PK) behavior of the patient, to calculate the optimal sampling schedule (OSS), which minimizes the number of blood samples per patient. The approach is illustrated with available PK data for gabapentin.

DESIGN: Retrospective proof of principles study using gabapentin PK data from a published clinical trial.

PATIENTS: Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36 hours after administration of a single dose of gabapentin 400 mg, and plasma concentrations were determined at 14 time points.

MEASUREMENTS AND MAIN RESULTS: When the PK profiles were different between subjects, the IDCs are dramatically different from each other and from the IDC for an "average" patient representing the patient population. The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range. An optimal sampling methodology based on the assumption-free Bayesian approach is used to distinguish the PK profile of an individual patient from the patient population. In the case of gabapentin, only two optimally selected test blood samples, at 1.5 and 6 hours after administration of a single doses, were necessary. The average sensitivity and the average specificity of the OSS was 99% and 96%, respectively.

CONCLUSION: IDCs display the risk of a patient violating the target concentration range for any dosage regimen. They can be used as a clinical-bedside decision-support tool in a patient-physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance. By using the assumption-free Bayesian approach and the OSS, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity. Prospective studies are being planned to validate the encouraging results. This approach can be extended to any drug if PK data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention.}, } @article {pmid23553589, year = {2013}, author = {Chamming's, F and Latorre-Ossa, H and Le Frère-Belda, MA and Fitoussi, V and Quibel, T and Assayag, F and Marangoni, E and Autret, G and Balvay, D and Pidial, L and Gennisson, JL and Tanter, M and Cuenod, CA and Clément, O and Fournier, LS}, title = {Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.}, journal = {European radiology}, volume = {23}, number = {8}, pages = {2079-2086}, pmid = {23553589}, issn = {1432-1084}, mesh = {Animals ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Elasticity ; *Elasticity Imaging Techniques ; Female ; Fibrosis/pathology ; Humans ; Mice ; Mice, Nude ; Necrosis ; Neoplasm Transplantation ; Pressure ; }, abstract = {OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology.

METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured.

RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1).

CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness.

KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.}, } @article {pmid23552903, year = {2013}, author = {Michel, T and Rieger, J and Anton, G and Bayer, F and Beckmann, MW and Durst, J and Fasching, PA and Haas, W and Hartmann, A and Pelzer, G and Radicke, M and Rauh, C and Ritter, A and Sievers, P and Schulz-Wendtland, R and Uder, M and Wachter, DL and Weber, T and Wenkel, E and Zang, A}, title = {On a dark-field signal generated by micrometer-sized calcifications in phase-contrast mammography.}, journal = {Physics in medicine and biology}, volume = {58}, number = {8}, pages = {2713-2732}, doi = {10.1088/0031-9155/58/8/2713}, pmid = {23552903}, issn = {1361-6560}, mesh = {Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Calcinosis/diagnostic imaging/*pathology ; Calcium Phosphates/metabolism ; *Darkness ; Female ; Humans ; Interferometry ; Mammography/*methods ; Middle Aged ; }, abstract = {We show that a distribution of micrometer-sized calcifications in the human breast which are not visible in clinical x-ray mammography at diagnostic dose levels can produce a significant dark-field signal in a grating-based x-ray phase-contrast imaging setup with a tungsten anode x-ray tube operated at 40 kVp. A breast specimen with invasive ductal carcinoma was investigated immediately after surgery by Talbot-Lau x-ray interferometry with a design energy of 25 keV. The sample contained two tumors which were visible in ultrasound and contrast-agent enhanced MRI but invisible in clinical x-ray mammography, in specimen radiography and in the attenuation images obtained with the Talbot-Lau interferometer. One of the tumors produced significant dark-field contrast with an exposure of 0.85 mGy air-kerma. Staining of histological slices revealed sparsely distributed grains of calcium phosphate with sizes varying between 1 and 40 μm in the region of this tumor. By combining the histological investigations with an x-ray wave-field simulation we demonstrate that a corresponding distribution of grains of calcium phosphate in the form of hydroxylapatite has the ability to produce a dark-field signal which would-to a substantial degree-explain the measured dark-field image. Thus we have found the appearance of new information (compared to attenuation and differential phase images) in the dark-field image. The second tumor in the same sample did not contain a significant fraction of these very fine calcification grains and was invisible in the dark-field image. We conclude that some tumors which are invisible in x-ray absorption mammography might be detected in the x-ray dark-field image at tolerable dose levels.}, } @article {pmid23549810, year = {2013}, author = {Eom, M and Lkhagvadorj, S and Oh, SS and Han, A and Park, KH}, title = {ROS1 expression in invasive ductal carcinoma of the breast related to proliferation activity.}, journal = {Yonsei medical journal}, volume = {54}, number = {3}, pages = {650-657}, pmid = {23549810}, issn = {1976-2437}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Proliferation ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Prognosis ; Protein-Tyrosine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Survival Analysis ; }, abstract = {PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast.

MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR).

RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant.

CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.}, } @article {pmid23548998, year = {2013}, author = {Bareggi, CM and Consonni, D and Galassi, B and Gambini, D and Locatelli, E and Visintin, R and Runza, L and Giroda, M and Sfondrini, MS and Onida, F and Tomirotti, M}, title = {Uncommon breast malignancies: presentation pattern, prognostic issue and treatment outcome in an Italian single institution experience.}, journal = {Tumori}, volume = {99}, number = {1}, pages = {39-44}, doi = {10.1177/030089161309900107}, pmid = {23548998}, issn = {2038-2529}, mesh = {Adenocarcinoma/*diagnosis/pathology ; Adenocarcinoma, Mucinous/*diagnosis/pathology ; Adult ; Aged ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Medullary/*diagnosis/pathology ; Carcinoma, Papillary/*diagnosis/pathology ; Disease-Free Survival ; Female ; Humans ; Italy/epidemiology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS AND BACKGROUND: Often neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series.

PATIENTS AND METHODS: Of 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome.

RESULTS: Rare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12-0.62; P = 0.002).

CONCLUSIONS: According to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.}, } @article {pmid23543486, year = {2013}, author = {Seok, JW and Kim, Y and An, YS and Kim, BS}, title = {The clinical value of tumor FDG uptake for predicting axillary lymph node metastasis in breast cancer with clinically negative axillary lymph nodes.}, journal = {Annals of nuclear medicine}, volume = {27}, number = {6}, pages = {546-553}, doi = {10.1007/s12149-013-0720-x}, pmid = {23543486}, issn = {1864-6433}, mesh = {Biological Transport ; Breast Neoplasms/diagnostic imaging/*metabolism/*pathology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Radionuclide Imaging ; Retrospective Studies ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the clinical value of 18F-fluorodeoxyglucose (FDG) uptake and the clinicopathological or immunohistochemical findings of the primary tumor to predict axillary lymph node (ALN) metastasis in breast cancer with clinically negative ALN.

METHODS: This study retrospectively enrolled 104 women (49.43 ± 9.9 years) having breast cancer with clinically negative ALN using all types of preoperative imaging modalities including ultrasonography, FDG positron emission tomography, and magnetic resonance imaging. All cases of breast cancer in this study were proven as invasive ductal carcinoma with ≥1 cm in size. The final diagnosis of ALN status was confirmed by permanent pathology after operation.

RESULTS: Among 104 breast cancers with clinically negative ALN, 21 breast cancers (20.2 %) were proven to have ALN metastasis. The ROC curve analysis showed that the best cut-off value of SUVmax for identifying ALN metastasis was 9.8 with 33.3 % sensitivity and 92.8 % specificity (AUC = 0.656; p = 0.027). The multivariable analysis revealed that primary tumors with SUVmax >9.8 (p = 0.011) and D2-40 positivity (p = 0.027) were independently associated with ALN metastasis with odds ratios of 5.516 (CI 1.475-20.6333) and 3.409 (CI 1.154-10.072), respectively.

CONCLUSION: Our study demonstrates that the incidence of ALN metastasis in even rigorously clinically evaluated breast cancer without suspiciously positive ALN is still not negligible, and while a high SUVmax of the primary tumor may be associated with a higher incidence of ALN metastasis in breast cancer with clinically negative ALN, a low SUVmax does not exclude ALN metastasis.}, } @article {pmid23540946, year = {2013}, author = {Jiang, L and Zhou, Y and Wang, Z and Lu, X and Chen, M and Zhou, C}, title = {Is there different correlation with prognostic factors between "non-mass" and "mass" type invasive ductal breast cancers?.}, journal = {European journal of radiology}, volume = {82}, number = {9}, pages = {1404-1409}, doi = {10.1016/j.ejrad.2013.03.006}, pmid = {23540946}, issn = {1872-7727}, mesh = {Adult ; Age Distribution ; Aged ; *Algorithms ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Contrast Media ; Diagnosis, Differential ; Female ; *Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness ; Observer Variation ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {PURPOSE: To investigate the association between non-mass type breast cancer and common clinical-pathological prognostic factors, compared with mass type breast cancer.

MATERIALS AND METHODS: After institutional review board approval, retrospective blind review of contrast-enhanced breast MRI was carried out for 88 histologically proven breast invasive ductal carcinoma (IDC) patients, presenting from January 2008 to December 2011. Two radiologists assessed the images of each lesion for the morphologic enhancement type [mass enhancement or non-mass-like enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two pathologists evaluated the histological grade of IDC, presence or absence of ductal carcinoma in situ (DCIS), lymph node status, presence or absence of vascular invasion, and expression status of estrogen receptor (ER)/progesterone receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer agreement was assessed with kappa test. Chi-square test and Spearman rank correlation were performed to explore the associations of morphologic enhancement type with the age, lesion size and the above pathological prognostic factors

RESULTS: Inter-observer agreement was excellent, with kappa>0.75. Morphologic enhancement type was significantly correlated with age (P=0.02), with NMLE more commonly seen in women less than 50 y/o. The size of NMLE was larger than that of mass and, with the increase of lesion size, proportion of NMLE among the cases increased (P=0.001). NMLE was also significantly correlated with low histologic grade of IDC (P=0.003) and presence of DCIS (P<0.001). There was no significant correlation between morphologic enhancement type and lymph node status, vascular invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in clumped enhancement than non-clumped (P=0.011). There was no correlation between enhancement distribution and prognostic factors

CONCLUSIONS: Non-mass type breast cancer may not necessarily have worse prognosis than the mass type, due to lower histological grade and closely related to DCIS component, although it may has larger tumor size. Clumped enhancement may have worse prognosis than non-clumped enhancement.}, } @article {pmid23539156, year = {2013}, author = {Mujtaba, SS and Ni, YB and Tsang, JY and Chan, SK and Yamaguchi, R and Tanaka, M and Tan, PH and Tse, GM}, title = {Fibrotic focus in breast carcinomas: relationship with prognostic parameters and biomarkers.}, journal = {Annals of surgical oncology}, volume = {20}, number = {9}, pages = {2842-2849}, doi = {10.1245/s10434-013-2955-0}, pmid = {23539156}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*mortality/pathology ; Carcinoma, Basal Cell/metabolism/*mortality/pathology ; Carcinoma, Ductal, Breast/metabolism/*mortality/pathology ; ErbB Receptors/metabolism ; Female ; Fibrosis/metabolism/*mortality/pathology ; Follow-Up Studies ; Humans ; Lymphocytes, Tumor-Infiltrating/*pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/metabolism/*mortality/pathology ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Fibrotic focus (FF) has been observed in breast cancers and is suggested to be an important prognostic marker. However, most of these observations were reported by the same group of investigators with similar sample cohort. The relationship of FF and molecular subtypes as well as its associated prognosis has not been elucidated.

METHODS: In this study, 450 cases of breast carcinomas were evaluated for the presence of FF and its association with clinicopathologic parameters and biomarkers.

RESULTS: FF was found in 18.7% of all consecutive cases. FF was associated positively with infiltrative margins (p=0.03) but negatively with extensive in situ component (p<0.001) and lymphocytic infiltration (p<0.001). It was positively associated with estrogen receptor (p=0.007) but negatively with human epidermal growth factor receptor 2 (HER2; p=0.001), epidermal growth factor receptor (p=0.021), Ki-67 (p=0.001), and c-kit (p=0.009). Concomitantly, FF was seen more commonly in luminal A cancers (p<0.001) but less so in luminal B (p=0.045) and HER2-overexpressing cancers (p=0.011). Analysis on patient outcome (median 41 months, range 1-69 months) indicated that FF was an independent poor prognostic factor for disease-free survival (hazard ratio=2.57; 95% confidence interval=1.267-5.214, p=0.009), particularly in the luminal B subtype.

CONCLUSIONS: The findings suggested that FF is associated with specific tumor morphology of an infiltrative, stellate pattern (typical invasive ductal carcinoma-not otherwise specified) rather than round, cellular mass with intense lymphocytic infiltrate (basal-like breast cancers). The poor prognostic implication of FF is additional and independent of other adverse prognostic indicators.}, } @article {pmid23535842, year = {2013}, author = {Arps, DP and Healy, P and Zhao, L and Kleer, CG and Pang, JC}, title = {Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast.}, journal = {Breast cancer research and treatment}, volume = {138}, number = {3}, pages = {719-726}, pmid = {23535842}, issn = {1573-7217}, support = {R01 CA107469/CA/NCI NIH HHS/United States ; R01 CA125577/CA/NCI NIH HHS/United States ; T32 CA083654/CA/NCI NIH HHS/United States ; U01 CA154224/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/mortality/*pathology/therapy ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Carcinoma, Lobular/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p < 0.001), be positive for estrogen receptor (96 vs. 70 %; p < 0.0001) and progesterone receptor (84 vs. 57 %; p < 0.0001), and less likely to overexpress HER-2/neu (12 vs. 23 %; p = 0.001). Despite these favorable prognostic features, IDC-L had a higher frequency of nodal metastases (51 vs. 34 %; p < 0.0001) and a worse 5-year disease-free survival than IDC (hazard ratio = 0.454; p = 0.0004). ILC and IDC-L had similar clinicopathologic features and outcomes. The proportion of the lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.}, } @article {pmid23534591, year = {2012}, author = {Pinto, AE and Pereira, T and Silva, GL and Ferreira, MC and André, S}, title = {[DNA ploidy is an independent prognostic biomarker in breast invasive ductal carcinoma].}, journal = {Acta medica portuguesa}, volume = {25}, number = {6}, pages = {399-407}, pmid = {23534591}, issn = {1646-0758}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Female ; Genetic Markers ; Humans ; Middle Aged ; *Ploidies ; Prognosis ; Prospective Studies ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate 'classic' prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free and overall survival in breast invasive ductal carcinoma with long-term follow-up.

MATERIAL AND METHODS: The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months (50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessed as established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.

RESULTS: There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greater size and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients < 40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease free survival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack of progesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediate differentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptors showed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation to overall survival) were indicators of worse prognosis.

CONCLUSION: Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker of long-term survival in breast invasive ductal carcinoma.}, } @article {pmid23529839, year = {2013}, author = {Benevides, L and Cardoso, CR and Tiezzi, DG and Marana, HR and Andrade, JM and Silva, JS}, title = {Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor.}, journal = {European journal of immunology}, volume = {43}, number = {6}, pages = {1518-1528}, doi = {10.1002/eji.201242951}, pmid = {23529839}, issn = {1521-4141}, mesh = {Antigens, CD/metabolism ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal/*immunology/pathology ; Cell Proliferation ; Cell Transformation, Neoplastic/immunology ; Chemokine CCL22/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Glucocorticoid-Induced TNFR-Related Protein/metabolism ; Humans ; Interleukin-17/genetics/*metabolism ; Neoplasm Invasiveness ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; Receptors, CCR6/metabolism ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*immunology ; Tumor Cells, Cultured ; Up-Regulation ; }, abstract = {Breast cancer is a leading cause of neoplasia-associated death in women worldwide. Regulatory T (Treg) and Th17 cells are enriched within some tumors, but the role these cells play in invasive ductal carcinoma (IDC) of the breast is unknown. We show that CD25(+) CD4(+) T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4, and CD103, indicating that tumor-infiltrating Treg cells are functional and possibly recruited by CCL22. Additionally, we observed upregulation of Th17-related molecules (IL-17A, RORC, and CCR6) and IL-17A produced by tumor-infiltrating CD4(+) and CD8(+) T lymphocytes. The angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor are possibly induced by IL-17 and indicative of poor disease prognosis. Treg and Th17 cells were synchronically increased in IDC patients, with positive correlation between Foxp3, IL-17A, and RORC expression, and associated with tumor aggressiveness. Therefore, Treg and Th17 cells can affect disease progression by Treg-cell-mediated suppression of the effector T-cell response, as indicated by a decrease in the proliferation of T cells isolated from PBMCs of IDC patients and induction of angiogenic factors by IL-17-producing Th17. The understanding of regulation of the Treg/Th17 axis may result in novel perspectives for the control of invasive tumors.}, } @article {pmid23528301, year = {2013}, author = {Fernández-Caggiano, M and Barallobre-Barreiro, J and Rego-Pérez, I and Crespo-Leiro, MG and Paniagua, MJ and Grillé, Z and Blanco, FJ and Doménech, N}, title = {Mitochondrial DNA haplogroup H as a risk factor for idiopathic dilated cardiomyopathy in Spanish population.}, journal = {Mitochondrion}, volume = {13}, number = {4}, pages = {263-268}, doi = {10.1016/j.mito.2013.03.005}, pmid = {23528301}, issn = {1872-8278}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*epidemiology/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Gene Frequency ; *Haplotypes ; Humans ; Male ; Middle Aged ; Risk Factors ; Spain/epidemiology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a structural heart disease with strong genetic background. The different single nucleotide polymorphisms (SNPs) that constitute mitochondrial haplogroups could play an important role in IDC progression. The aim of this study was to test frequencies of mitochondrial haplogroups in healthy controls (n=422) and IDC patients (n=304) of a Caucasian Spanish population. To achieve this, ten major European haplogroups were identified. Frequencies and Odds Ratios for the association between IDC and haplogroups were calculated in both groups. We found that compared to healthy controls, the prevalence of haplogroup H was significantly higher in IDC patients (40.0% vs 50.7%, p-value=0.040).}, } @article {pmid23526630, year = {2013}, author = {Tjomsland, V and Ellegård, R and Burgener, A and Mogk, K and Che, KF and Westmacott, G and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells.}, journal = {European journal of immunology}, volume = {43}, number = {6}, pages = {1470-1483}, pmid = {23526630}, issn = {1521-4141}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; R01 AI052731/AI/NIAID NIH HHS/United States ; R37 AI052731/AI/NIAID NIH HHS/United States ; }, mesh = {Antibodies, Blocking/metabolism ; Antigen Presentation ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Complement System Proteins/*immunology ; Dendritic Cells/*immunology ; Endocytosis ; HIV Infections/*immunology ; HIV-1/*immunology ; Histocompatibility Antigens Class I/*immunology ; Humans ; Integrin beta Chains/immunology ; Lectins, C-Type/immunology ; Lymphocyte Activation ; Mannose Receptor ; Mannose-Binding Lectins/immunology ; Protein Binding ; Receptors, Cell Surface/immunology ; Receptors, Complement/immunology ; }, abstract = {Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and β7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery.}, } @article {pmid23523041, year = {2013}, author = {Niu, Y and Wang, S and Liu, T and Zhang, T and Wei, X and Wang, Y and Jiang, L}, title = {Expression of centrosomal tubulins associated with DNA ploidy in breast premalignant lesions and carcinoma.}, journal = {Pathology, research and practice}, volume = {209}, number = {4}, pages = {221-227}, doi = {10.1016/j.prp.2012.12.006}, pmid = {23523041}, issn = {1618-0631}, mesh = {Aneuploidy ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology ; Centrosome/*chemistry ; Chi-Square Distribution ; Disease Progression ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Hyperplasia ; Neoplasm Grading ; Neoplasm Invasiveness ; *Ploidies ; Precancerous Conditions/*chemistry/genetics/pathology ; Tubulin/*analysis ; }, abstract = {The centrosome plays an essential role in chromosomal segregation during cell division. Centrosome dysfunction might lead to aneuploidy and chromosomal instability. Invasive breast tumors with centrosome amplification often show aneuploidy. Flow cytometry (FCM) was used to examine the aneuploidy rate in 30 cases of each of the following seven tissue types: normal breast tissue, usual ductal hyperplasia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ, high-grade ductal carcinoma in situ, low-grade invasive ductal carcinoma, and high-grade invasive ductal carcinoma. Centrosomal α, γ-tubulin expression was examined by FCM immunofluorescence and compared between diploid and aneuploid cells. The aneuploidy rate was 0, 6.7%, 26.7%, 30.0%, 46.7%, 56.7%, and 86.7%, respectively, in the seven tissue types. The percentage of cells expressing α- and γ-tubulins was significantly different between the seven groups, and the positive rate of α- and γ-tubulin expression in ADH, DCIS and IDC was higher than that in NBT and UDH. The percentage of cells expressing α- and γ-tubulins in the diploid state was significantly lower than that in the aneuploid state. Expression of centrosomal α- and γ-tubulins seems to be associated with DNA ploidy in breast premalignant lesions and carcinoma during the progression of breast cancer.}, } @article {pmid23522309, year = {2013}, author = {Ramírez-Torres, N and Asbun-Bojalil, J and Hernández-Valencia, M}, title = {[Pregnancy and breast cancer].}, journal = {Cirugia y cirujanos}, volume = {81}, number = {2}, pages = {98-107}, pmid = {23522309}, issn = {2444-054X}, mesh = {Adult ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*epidemiology/pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/pathology/therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Delayed Diagnosis ; Disease-Free Survival ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Infant, Newborn ; Mastectomy/methods ; Mexico/epidemiology ; Middle Aged ; Neoadjuvant Therapy ; Neoplasms, Hormone-Dependent/epidemiology/pathology/therapy ; Pregnancy ; Pregnancy Complications, Neoplastic/*epidemiology/pathology/therapy ; Pregnancy Outcome ; Prognosis ; Puerperal Disorders/epidemiology/pathology/therapy ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Tamoxifen/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: association of breast cancer and pregnancy is not common. The objective of this investigation was to evaluate the pregnancy, young age, stage, treatment, prognosis and mortality of women with breast cancer during pregnancy.

METHODS: retrospective analysis from March 1992 to February 2009, 16 patients were included with breast cancer and pregnancy. They were analized: histological characteristic of tumor, therapeutic response of the oncological treatment, evolution of the pregnancy. From of baby born: Apgar and weight. The woman's mortality with breast cancer during pregnancy was evaluated for age group and for interval of time between late pregnancy and diagnosis posterior of breast cancer and pregnancy.

RESULTS: characteristic predominant clinicohistological: stage III (81.2%), T3-T4 (75%), N+ 93.7%, invasive ductal carcinoma (87.5%), histological grade 2-3 (93.7%), receptor estrogeno positive (43.7%); RPpositive (25%); HER-2/neu positive (31.2%). 27 chemotherapy cycles were applied with 5-fluorouracil, epirubicin and cyclophosphamide during the second or third trimester of the pregnancy, there were not severe adverse effects for the mothers and the baby born exposed to chemotherapy. The mean time to disease recurrence was 18.8 months (range, 6-62 months). The rate of mortality for specific age (< 35 years) was of 31.3% (p = 0.358). From the 16 patients, 7 have died and 9 were live without evidence of disease.

CONCLUSIONS: the advanced stage and the number of affected axillary lymph node more than the age was predictors of worse pronostic influencing the relapse and mortality of the young patients with breast cancer and pregnancy.}, } @article {pmid23520664, year = {2012}, author = {Jana, D and Sarkar, DK and Maji, A and Chikkala, BR and Hassanujjaman, S and Mukhopadhyay, M and Ganguly, S}, title = {Can cyclo-oxygenase-2 be a useful prognostic and risk stratification marker in breast cancer?.}, journal = {Journal of the Indian Medical Association}, volume = {110}, number = {7}, pages = {429-433}, pmid = {23520664}, issn = {0019-5847}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal/*genetics/pathology ; Cyclooxygenase 2/*genetics ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Genetic Markers/*genetics ; Humans ; Lymphatic Metastasis/pathology ; Neoplasm Staging ; Neoplasms, Hormone-Dependent/genetics/pathology ; Prognosis ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Tumor Burden/physiology ; }, abstract = {Cyclo-oxygenase-2 (COX-2) is a prostaglandin synthease that catalyses the synthesis of prostaglandin G2 (PGG2) and PGH2 from arachidonic acid. COX-2 plays an important role in tumourigenesis of different carcinoma types and it is thought to take part in breast carcinoma. In this study, the aim was to investigate the relationship of COX-2 with clinical parameters such as menopausal status, tumour size, grade, nodal status, Nottingham prognostic index (NPI), oestrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER-2/ neu). The patients were divided into two groups, first group (group A) comprised 57 primary breast cancer patients and the second group (group B) comprised control group 27 patients consisting of fibro-adenoma and benign breast disease. In control groups COX-2 (0%) is not over expressed and we observed that high frequency of COX-2 (73.68%) over expressed in breast carcinoma. In high grade, large tumour size and positive lymph node metastasis, COX-2 expression rate was 78.6%, 59.5% and 90.5% respectively. COX-2 expression is directly correlated with ER negative (88.1%, p = 0.001) and also associated with higher NPI value (78.6%, p = 0.006). In invasive ductal carcinoma (IDC) COX-2 over expression had a significant relationship with HER-2/neu over expression (p < 0.001). The results indicated that COX-2 over expression correlates with aggressive phenotypic features, such as high histological grade, large tumour size, higher NPI value, ER negativity and HER-2/neu positivity.}, } @article {pmid23515911, year = {2013}, author = {Parker, A and Schroen, AT and Brenin, DR}, title = {MRI utilization in newly diagnosed breast cancer: a survey of practicing surgeons.}, journal = {Annals of surgical oncology}, volume = {20}, number = {8}, pages = {2600-2606}, doi = {10.1245/s10434-013-2934-5}, pmid = {23515911}, issn = {1534-4681}, support = {P30 CA044579/CA/NCI NIH HHS/United States ; }, mesh = {Breast Density ; Breast Neoplasms/*diagnosis/diagnostic imaging/genetics ; Carcinoma/*diagnosis/diagnostic imaging/genetics ; Chi-Square Distribution ; Data Collection ; Female ; Humans ; Institutional Practice/statistics & numerical data ; Logistic Models ; Magnetic Resonance Imaging/*statistics & numerical data ; Mammary Glands, Human/abnormalities ; *Practice Patterns, Physicians' ; Private Practice/statistics & numerical data ; Radiography ; Specialization/*statistics & numerical data ; }, abstract = {BACKGROUND: Whereas guidelines supporting breast MRI in high-risk screening exist, guidelines for MRI use in newly diagnosed breast cancer are lacking. We, therefore, conducted a study of breast surgeons to determine practice beliefs surrounding MRI use in newly diagnosed breast cancer.

METHODS: A survey sent to 2,274 American Society of Breast Surgeons members in December 2010 queried routine MRI use (defined as >75 % of time) in specific clinical scenarios. Analyses were performed by respondent practice setting, practice volume, and practice specialization. Descriptive statistics and subgroup analysis using a χ(2) and logistic regression were used.

RESULTS: Responses from 1,012 surgeons (45.5 % response rate) were eligible for analysis. Respondents represented diverse practice settings (20 % academic, 72 % private practice) and volume (≤50 new breast cancer patients, 36 %; 51-100, 26 %; 101-200, 25 %; >200, 13 %). Also, 41 % of surgeons indicated routine MRI use for newly diagnosed patients, with higher rates of use among surgeons from high-volume practices, high specialization, and private practice. Greater consensus in routine MRI use was seen in the setting of extreme mammographic density (87.9 %), strong family history of breast cancer (73.4 %), and invasive lobular carcinoma (69.4 %). Responses were increasingly discordant in setting of pursuing breast conservation (47.4 %), invasive ductal carcinoma (41.8 %), and ductal carcinoma in situ (37.2 %). Personal experience was the most commonly cited influence on MRI use.

CONCLUSIONS: Divergent responses in MRI use in newly diagnosed breast cancer reflect clinical uncertainty and variable practice beliefs among breast surgeons. Such diverging practice patterns highlight areas where clinical research and guidelines may be most helpful.}, } @article {pmid23515845, year = {2013}, author = {Figueiredo, P and Morais, P and Vilas-Boas, JP and Fernandes, RJ}, title = {Changes in arm coordination and stroke parameters on transition through the lactate threshold.}, journal = {European journal of applied physiology}, volume = {113}, number = {8}, pages = {1957-1964}, pmid = {23515845}, issn = {1439-6327}, mesh = {Adolescent ; *Anaerobic Threshold ; Arm/*physiology ; Biomechanical Phenomena ; Female ; Humans ; Lactic Acid/*blood ; Male ; Swimming/*physiology ; Young Adult ; }, abstract = {The purpose of the present study was to understand the energetic, biomechanical and coordinative changes occurring throughout the transition of the lactate threshold. Twelve high-level swimmers (six males and six females) performed a paced intermittent incremental protocol of 7 × 200 m (0.05 m s(-1) increments and 30 s intervals). The stroking parameters (stroke rate and stroke length) and the index of coordination (IdC) were assessed by analysis of video recordings from aerial and underwater side-view cameras. Energy cost (C) was determined by the ratio energy expenditure/velocity. Energy expenditure was determined by measuring oxygen uptake VO2 and blood lactate concentrations ([La(-)]). The swimming velocity at the inflection point of stroke rate, stroke length, IdC, VO2, and [La(-)] was determined (m s(-1)). The results showed that stroke rate, stroke length, IdC, VO2, and [La(-)] all exhibited inflection point as a function of swimming velocity, and these velocities were highly correlated with the velocity at [La(-)]inflex (1.35 ± 0.07 m s(-1); R = 0.99, P < 0.001). Furthermore, these values were not significantly different (P > 0.05), and Bland-Altman plots estimations were almost unbiased. These findings seem to confirm that as swimming velocity increases and lactate threshold is surpassed, it induces changes in stroke mechanics and organization suggesting an important biomechanical, coordinative and metabolic boundary between moderate and heavy intensity domains.}, } @article {pmid23508227, year = {2012}, author = {Shankayi, Z and Firoozabadi, SM}, title = {Antitumor efficiency of electrochemotherapy by high and low frequencies and repetitive therapy in the treatment of invasive ductal carcinoma in BALB/c mice.}, journal = {Cell journal}, volume = {14}, number = {2}, pages = {110-115}, pmid = {23508227}, issn = {2228-5806}, abstract = {OBJECTIVE: In electrochemotherapy (ECT), there is an unpleasant sensation of muscle contraction when using a low frequency (1 Hz). Therefore, by increasing the pulse frequency above the tetanic frequency this painful sensation can be reduced. The aim of the present study is to compare the treatment efficiencies of low and high frequency ECT, and estimate the effect of its repeated sessions.

MATERIALS AND METHODS: We transplanted invasive ductal carcinoma into the flanks of female Balb/c mice. ECT was performed on the mice by the use of 8 pulses, 1000 v/cm, of 100 µs duration at 1 Hz and 5 kHz repetition frequencies along with intra-tumoral injections of bleomycin. We also used this ECT protocol for the second therapy session six days after tumour regrowth. The effect of treatment was measured by calculating the tumor volumes for 24 days following treatment. Statistical analysis was performed with ANOVA.

RESULTS: ECT at 1 Hz and 5 kHz pulse frequencies demonstrated significant inhibition of tumor growth, but after the first treatment the tumours began to regrow. Repetitive ECT sessions increased the curability of tumors up to 40% in the group treated by 1 Hz frequency and 60% in the group treated with 5 kHz frequency.

CONCLUSION: Our results demonstrate that the effects of 1 Hz and 5 kHz pulse repetition frequencies are comparable for inhibited tumour growth. Repetitive treatment can improve the effectiveness of ECT.}, } @article {pmid23507669, year = {2012}, author = {AbdullGaffar, B and Ghazi, E and Mohamed, E and Hamza, D}, title = {Breast metaplastic carcinoma with unusual small cell component.}, journal = {Breast disease}, volume = {34}, number = {1}, pages = {19-24}, doi = {10.3233/BD-130346}, pmid = {23507669}, issn = {1558-1551}, mesh = {Adenocarcinoma/*pathology ; Adult ; Breast Neoplasms/*pathology ; Cellular Structures/pathology ; Female ; Humans ; Immunohistochemistry ; Metaplasia ; Sarcoma, Small Cell/*pathology ; Sarcoma, Synovial/*pathology ; }, abstract = {Small round cell mesenchymal component in breast metaplastic carcinoma is very rare and could be confused with other small round cell neoplasms of the breast. Synovial sarcoma exceptionally involves the breast and rarely may show a poorly differentiated small round cell component. These unusual small round cell components in biphasic metaplastic carcinoma and synovial sarcoma as well as collision tumor of ductal carcinoma and Ewing sarcoma might have overlapping clinical, histologic and immunohistochemical features which make distinction between these neoplasms difficult for the pathologists. Separation between these neoplasms is important for the treating oncologists because each tumor type has different prognostic implications and treatment modalities. Certain immunohistochemical markers might help, but cytogenetics study is the final confirmatory test. We report a unique example of a biphasic breast neoplasm in a 43-year-old woman that showed a combination of a minor central component of adenocarcinoma distinct from the bulky surrounding component of small round cell tumor. The histologic and immunohistochemical features were overlapping between metaplastic carcinoma, poorly differentiated synovial sarcoma and a composite collision tumor of invasive ductal carcinoma and Ewing sarcoma.}, } @article {pmid23506949, year = {2013}, author = {Córdoba, EV and Pion, M and Rasines, B and Filippini, D and Komber, H and Ionov, M and Bryszewska, M and Appelhans, D and Muñoz-Fernández, MA}, title = {Glycodendrimers as new tools in the search for effective anti-HIV DC-based immunotherapies.}, journal = {Nanomedicine : nanotechnology, biology, and medicine}, volume = {9}, number = {7}, pages = {972-984}, doi = {10.1016/j.nano.2013.03.004}, pmid = {23506949}, issn = {1549-9642}, mesh = {Biomarkers/metabolism ; Cell Death/drug effects ; Cell Differentiation/drug effects ; Cell Movement/drug effects ; Cytokines/metabolism ; Dendrimers/*chemistry/pharmacology ; Dendritic Cells/drug effects/*immunology/metabolism ; HIV/drug effects/*immunology ; HIV Infections/*immunology/*therapy ; Humans ; *Immunotherapy ; Maltose/chemistry ; Peptides/immunology ; Phenotype ; T-Lymphocytes/cytology/drug effects ; }, abstract = {UNLABELLED: Dendritic cells (DC), which play a major role in development of cell-mediated immunity, represent opportunities to develop novel anti-HIV vaccines. Dendrimers have been proposed as new carriers to ameliorate DC antigen loading and in this way, we have determined the potential use of maltose decorated neutrally and positively charged G4 glycodendrimers. Thus, immunostimulatory properties of these glycodendrimers on human DC were evaluated in the context of HIV infection. We have demonstrated that DC treated with glycodendrimers were fully functional with respect to viability, maturation and HIV-derived antigens uptake. Nevertheless, iDC and mDC phenotypes as well as mDC functions such as migration ability and cytokines profile production were changed. Our results showed the potential carrier properties of glycodendrimers to activate the immune system by the way of DC stimulation. This is the first study for exploring the use of maltose-functionalized dendrimers-peptides complexes as a potential DC-based vaccine candidate.

FROM THE CLINICAL EDITOR: In this paper, maltose-functionalized dendrimer-peptide complexes are demonstrated to activate the immune system by way of dendritic cell (DC) stimulation. DC vaccination using this methodology may be applicable to a variety of conditions, including infections and potentially cancer.}, } @article {pmid23490334, year = {2013}, author = {Biglia, N and Maggiorotto, F and Liberale, V and Bounous, VE and Sgro, LG and Pecchio, S and D'Alonzo, M and Ponzone, R}, title = {Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {39}, number = {5}, pages = {455-460}, doi = {10.1016/j.ejso.2013.02.007}, pmid = {23490334}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*pathology/radiotherapy/*surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/*surgery ; Carcinoma, Lobular/*pathology/radiotherapy/*surgery ; Chi-Square Distribution ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Logistic Models ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Reoperation ; Retrospective Studies ; Risk Factors ; Sentinel Lymph Node Biopsy ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE OF THE STUDY: A retrospective analysis on 1407 patients with invasive ductal carcinoma (IDC) and 243 invasive lobular carcinoma (ILC) was performed in order to compare the histological features, the immunohistochemical characteristics, the surgical treatment and the clinical outcome in the two groups.

RESULTS: ILC seems to be more likely multifocal, estrogen receptor positive, HER-2 negative and to have a lower proliferative index compared to IDC. ILC, when treated with conservative surgery, required more frequently re-excision and/or mastectomy because of positive resection margins. No difference was observed in terms of 5-year disease free survival and local relapse free survival between the two groups, in the whole series and in the subgroup of patients treated with breast-conserving treatment.

CONCLUSION: ILC can be safely treated with conservative surgery but a more accurate preoperative evaluation of tumor size and multifocality could be advocated, in order to reduce the re-excision rate.}, } @article {pmid23486657, year = {2012}, author = {Dominguez-Castells, R and Arellano, R}, title = {Effect of different loads on stroke and coordination parameters during freestyle semi-tethered swimming.}, journal = {Journal of human kinetics}, volume = {32}, number = {}, pages = {33-41}, pmid = {23486657}, issn = {1640-5544}, abstract = {The aim of this study was to analyse to what extent the use of different loads modifies freestyle stroke and coordination parameters during semi-tethered swimming, and to examine whether those changes are positive or negative to swimming performance. First, behaviour of swimming speed (v), stroke rate (SR) and stroke length (SL) with increasing loads was examined. Secondly, mean and peak speed of propulsive phases (propvmean and propvpeak) were analysed, as well as the relative difference between them (%v). Finally, index of coordination (IdC) was assessed. Eighteen male swimmers (22.10±4.31years, 1.79±0.07m, 76.74±9.00kg) performed 12.5m maximal sprints, pulling a different load each trial (0, 1.59, 2.21, 2.84, 3.46, 4.09, 4.71, 5.34, 5.96, 6.59, 7.21 and 7.84kg). Rest between repetitions was five minutes. Their feet were tied together, keeping a pull-buoy between legs and isolating the upper limb action. A speedometer was used to measure intra-cycle speed and the test was recorded by a frontal and a lateral underwater cameras. Variables v and SL decreased significantly when load increased, while SR remained constant (p<0.05). Propvmean and propvpeak decreased significantly with increasing loads (p<0.05). In contrast, %v grew when load rose (r = 0.922, p<0.01), being significantly different from free swimming above 4.71kg. For higher loads, swimmers did not manage to keep a constant velocity during a complete trial. IdC was found to increase with loads, significantly from 2.84kg (p<0.05). It was concluded that semi-tethered swimming is one training method useful to enhance swimmers' performance, but load needs to be individually determined and carefully controlled.}, } @article {pmid23479708, year = {2013}, author = {Lattin, GE and Jesinger, RA and Mattu, R and Glassman, LM}, title = {From the radiologic pathology archives: diseases of the male breast: radiologic-pathologic correlation.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {33}, number = {2}, pages = {461-489}, doi = {10.1148/rg.332125208}, pmid = {23479708}, issn = {1527-1323}, mesh = {Adult ; Aged ; Breast Neoplasms, Male/*diagnosis ; Gynecomastia/*diagnosis ; Humans ; Male ; Mammography/*methods ; Middle Aged ; }, abstract = {Male breast disease includes a variety of benign and malignant conditions, many of which are hormonally influenced. Gynecomastia and skin lesions account for the majority of conditions in symptomatic men with a palpable abnormality, and these conditions should be accurately recognized. Imaging patterns of gynecomastia include nodular, dendritic, and diffuse patterns. Histopathologically, the nodular and dendritic patterns correlate with the florid and quiescent (fibrotic) phases of gynecomastia, respectively. The diffuse pattern may have features of both phases and is associated with exposure to exogenous estrogen. Benign-appearing palpable masses in male patients should be approached cautiously, given the overlapping morphologic features of benign and malignant tumors. In addition to gynecomastia, other benign male breast tumors include lipoma, pseudoangiomatous stromal hyperplasia, granular cell tumor, fibromatosis, myofibroblastoma, schwannoma, and hemangioma. Male breast cancer accounts for 1% of all breast carcinomas. Invasive ductal carcinoma accounts for the majority of cases in adult males and typically appears as a subareolar mass without calcifications that is eccentric to the nipple. Other epithelial and mesenchymal tumors that may occur, albeit not as commonly as in women, include papillary carcinoma, invasive lobular carcinoma, adenoid cystic carcinoma, liposarcoma, dermatofibrosarcoma, pleomorphic hyalinizing angiectatic tumor, basal cell carcinoma of the nipple, hematopoietic malignancies, and secondary tumors. Knowledge of the natural history, clinical characteristics, and imaging features of tumors that occur in the male breast will help narrow the radiologic differential diagnosis and optimize treatment.}, } @article {pmid23479571, year = {2013}, author = {McKimmie, CS and Singh, MD and Hewit, K and Lopez-Franco, O and Le Brocq, M and Rose-John, S and Lee, KM and Baker, AH and Wheat, R and Blackbourn, DJ and Nibbs, RJ and Graham, GJ}, title = {An analysis of the function and expression of D6 on lymphatic endothelial cells.}, journal = {Blood}, volume = {121}, number = {18}, pages = {3768-3777}, doi = {10.1182/blood-2012-04-425314}, pmid = {23479571}, issn = {1528-0020}, support = {ETM/276/CSO_/Chief Scientist Office/United Kingdom ; 19656/ARC_/Arthritis Research UK/United Kingdom ; G0901113/MRC_/Medical Research Council/United Kingdom ; 19656/VAC_/Versus Arthritis/United Kingdom ; G1001724/MRC_/Medical Research Council/United Kingdom ; ETM/115/CSO_/Chief Scientist Office/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; RG/09/005/27915/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Animals ; CHO Cells ; Cell Communication/genetics/immunology ; Cell Differentiation/genetics/immunology ; Cells, Cultured ; Cricetinae ; Cricetulus ; Dendritic Cells/immunology/metabolism/physiology ; Endothelial Cells/immunology/*metabolism ; HEK293 Cells ; Humans ; Inflammation/genetics/immunology/metabolism ; Neoplasms/genetics/immunology/metabolism ; Receptors, CCR10/analysis/*genetics/metabolism/*physiology ; Transfection ; }, abstract = {The mechanisms by which CC chemokine receptor (CCR)7 ligands are selectively presented on lymphatic endothelium in the presence of inflammatory chemokines are poorly understood. The chemokine-scavenging receptor D6 is expressed on lymphatic endothelial cells (LEC) and contributes to selective presentation of CCR7 ligands by suppressing inflammatory chemokine binding to LEC surfaces. As well as preventing inappropriate inflammatory cell attachment to LECs, D6 is specifically involved in regulating the ability of LEC to discriminate between mature and immature dendritic cells (DCs). D6 overexpression reduces immature DC (iDC) adhesion to LECs, whereas D6 knockdown increases adhesion of iDCs that displace mature DCs. LEC D6 expression is regulated by growth factors, cytokines, and tumor microenvironments. In particular, interleukin-6 and interferon-γ are potent inducers, indicating a preferential role for D6 in inflamed contexts. Expression of the viral interleukin-6 homolog from Kaposi sarcoma-associated herpesvirus is also sufficient to induce significant D6 upregulation both in vitro and in vivo, and Kaposi sarcoma and primary effusion lymphoma cells demonstrate high levels of D6 expression. We therefore propose that D6, which is upregulated in both inflammatory and tumor contexts, is an essential regulator of inflammatory leukocyte interactions with LECs and is required for immature/mature DC discrimination by LECs.}, } @article {pmid23478274, year = {2013}, author = {de Melo Rêgo, MJ and Cordeiro, MF and Cavalcanti, Cde L and de Carvalho Junior, LB and Beltrão, EI}, title = {Immunohistochemiluminescence detection: a quantitative tool in breast cancer HER-2 status evaluation.}, journal = {Disease markers}, volume = {34}, number = {5}, pages = {373-377}, doi = {10.3233/DMA-130981}, pmid = {23478274}, issn = {1875-8630}, mesh = {Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry/methods ; Luminescence ; Luminescent Measurements/*methods ; Prognosis ; Receptor, ErbB-2/*analysis ; }, abstract = {Her-2 status evaluation in breast cancer has prognostic and treatment response value but its interobserver variation among pathologists is a problem since it is not quantitatively assayed. This study presents an immunohistochemiluminescence method to quantify Her-2 in breast cancer. Anti-Her-2 antibody was conjugated to acridinium ester (AE) and used to evaluate/quantify Her-2 status in breast Invasive Ductal Carcinoma (IDC, n=50) comparing with traditional immunohistochemistry. Anti-HER-2-AE results were expressed in Relative Lights Units (RLU) and showed to be able to distinguish and quantify the differences between the three groups of Her-2 status. 3+ Her-2 status presented the highest RLU (246,982 × 10(3) ± 2.061 × 10(3)) compared to 2+ (76,146 × 10(3) ± 0.290 × 10(3)), negative (27,415 × 10(3) ± 1.445 × 10(3)) and normal tissues (27,064 × 10(3) ± 2.060). Status differences were significant between 3+ and 2+ (p=0.0025); 2+ and negative (p=0.0003), and +3 and +1 (p=0.0001) beside this, normal breast control RLU was 27,064 × 10(3) ± 2,060 × 10(3), similar to negative cases. Results showed that anti-HER-2-AE conjugate was effective in breast tumors Her-2 status evaluation, allowing its quantitative establishment to consequently decrease the subjectivity in prognostic and predictive information intrinsic to this test.}, } @article {pmid23473275, year = {2013}, author = {Cooper, A and Schupbach, A and Chan, L}, title = {A case of male invasive breast carcinoma presenting as a non-healing wound.}, journal = {Dermatology online journal}, volume = {19}, number = {2}, pages = {5}, pmid = {23473275}, issn = {1087-2108}, mesh = {Adult ; Breast Neoplasms, Male/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Humans ; Male ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Wound Healing/physiology ; }, abstract = {Breast cancer in male patients accounts for less than 1 percent of malignancies in men. When compared to women, men with breast cancer are, on average, older, diagnosed at a more advanced stage, more likely to be hormone-receptor positive, less likely to overexpress HER2/neu, and have a lower overall survival. Owing to the paucity of data, male breast cancer treatment is typically guided by trials from female breast cancer. We report a case of invasive ductal carcinoma in a male patient with the initial presenting morphology of a non-healing chest wound. Interestingly, immunostaining identified positivity for estrogen receptor, progesterone receptor, and HER2/neu in the patients tumor. Although rare, breast carcinoma is an important consideration in any male with a breast mass, retracted nipple, or ulceration, as was seen in our patient.}, } @article {pmid23469238, year = {2013}, author = {Catteau, X and Simon, P and Vanhaeverbeek, M and Noël, JC}, title = {Variable stromal periductular expression of CD34 and smooth muscle actin (SMA) in intraductal carcinoma of the breast.}, journal = {PloS one}, volume = {8}, number = {3}, pages = {e57773}, pmid = {23469238}, issn = {1932-6203}, mesh = {Actins/genetics/metabolism ; Antigens, CD34/genetics/metabolism ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Myofibroblasts/metabolism/*pathology ; Necrosis/*genetics/pathology ; Neoplasm Grading ; Neoplasm Invasiveness ; Stromal Cells/metabolism/*pathology ; }, abstract = {In breast carcinoma, the stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness. However, this hypothesis remains controversial, with some authors describing the loss of CD34 fibrocytes in the absence of SMA myofibroblastic-like cells in the stroma of invasive carcinoma. Others have also described the disappearance of CD34 fibrocytes from in situ carcinoma. To clarify this issue, we compared the distribution of CD34 fibrocytes and SMA reactive myofibroblasts between stromal areas of tumor-free mammary tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). In addition to 28 IDC, 300 normal duct-lobular units and 600 ducts with DCIS (158 low-grade, 266 intermediate, and 176 high-grade) were scored. The relationships between staining patterns and different histological features (grade of DCIS and presence or absence of necrosis) were compared. Loss of CD34 expression and acquisition of SMA expression were more frequent in high-grade in situ lesions than in intermediate and low-grade lesions (p<0.001). When necrosis was found in association with grade 2 or 3 DCIS, the decrease in CD34 expression was higher than in lesions without necrosis and that independently of the grade of DCIS (p<0.05). Necrosis did not appear to play a significant role in the expression of SMA (p = 0.35). In all cases, the stroma of invasive carcinomas showed a complete loss of CD34 fibrocytes. Future research on both CD34 fibrocytes and mechanisms stromal changes are essential in the future and may potentially lead to new treatment approaches.}, } @article {pmid23468622, year = {2013}, author = {Gupta, AP and Chin, WH and Zhu, L and Mok, S and Luah, YH and Lim, EH and Bozdech, Z}, title = {Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum.}, journal = {PLoS pathogens}, volume = {9}, number = {2}, pages = {e1003170}, pmid = {23468622}, issn = {1553-7374}, mesh = {Animals ; *Epigenesis, Genetic ; *Gene Expression Regulation, Developmental ; Genome, Protozoan ; Histones/genetics ; Life Cycle Stages/*physiology ; Plasmodium falciparum/*genetics ; Real-Time Polymerase Chain Reaction ; Time Factors ; Transcription, Genetic ; }, abstract = {Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5' ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.}, } @article {pmid23468259, year = {2013}, author = {Wojnar, A and Bartosz Puła, B and Podhorska-Okołów, M and Dzięgiel, P}, title = {Discrepancies between HER2 assessment from core needle biopsies and surgical specimens of invasive ductal breast carcinoma.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {22}, number = {1}, pages = {27-31}, pmid = {23468259}, issn = {1899-5276}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Female ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Receptor, ErbB-2/*metabolism ; }, abstract = {BACKGROUND: The assessment of HER2 status is particularly important for qualifying patients for trastuzumab treatment of invasive ductal breast carcinoma (IDC). HER2 assessment in core needle biopsies (CNBs) of IDC could contribute to a better therapy schedule.

OBJECTIVES: The study aimed at examining the relationship between HER2 immunohistochemistry assessment scores in paired CNBs and whole tissue sections of IDC.

MATERIAL AND METHODS: The study was performed on paired samples of CNBs and whole tissue sections from 49 IDC patients operated on at the Lower Silesian Oncology Center in Wroclaw, Poland.

RESULTS: Discrepancies in HER2 scores were noted in eleven (22.45%) of the paired samples analyzed. Three cases (6.12%) were underscored in the CNB specimens as compared to the surgical HER2 specimens, whereas eight cases (16.33%) were overscored in the CNB specimens.

CONCLUSIONS: Based on the high level of discrepancy between the tested pairs of IDC tissues, the authors recommend caution in assessing HER2 in CNB tissue specimens as a standard procedure. Wherever possible whole tissue sections should be utilized for HER2 assessment.}, } @article {pmid23466672, year = {2013}, author = {Kawada, N and Uehara, H and Takada, R and Yamai, T and Fukutake, N and Katayama, K and Takenaka, A and Nagata, S and Tomita, Y}, title = {Microinvasion of high-grade pancreatic intraepithelial neoplasia.}, journal = {Case reports in gastroenterology}, volume = {7}, number = {1}, pages = {30-36}, pmid = {23466672}, issn = {1662-0631}, abstract = {High-grade pancreatic intraepithelial neoplasia (PanIN-3) is recognized as a precursor lesion of invasive ductal carcinoma (IDC). However, histological evidence that PanIN-3 invades beyond the basement membrane of pancreatic ductal epithelium, that is, the moment PanIN-3 becomes IDC, has not been captured yet. This may be because PanINs which are microscopic papillary or flat lesion rarely develop clinical symptoms and are not detectable on imaging examination. On the other hand, most IDCs were found in the advanced stage with massive invasion. In this report, PanIN-3 obstructed several branch pancreatic ducts and subsequently caused pancreatitis which developed clinical symptom and was detectable as a pancreatic mass in imaging studies. A 65-year-old woman was referred to our institution for further examination of her repeated pancreatitis. Abdominal ultrasound revealed a low echoic mass of 13 mm in diameter in the pancreatic body without upstream dilatation of the main pancreatic duct (MPD). Endoscopic retrograde pancreatography showed a strictured segment of 2 mm in length in the MPD at the pancreatic body. Cytological examination of pancreatic juice revealed adenocarcinoma and distal pancreatectomy was performed. A resected specimen revealed a whitish mass of 15 mm in diameter in the pancreatic body, which was identified as pancreatitis by histological examination. Papillary growth of PanIN-3 was seen mainly in the branch ducts. Each PanIN-3 was located separately in the branch ducts with normal epithelia in the MPD between them. In three adjacent branch ducts, PanIN-3 was observed to be invading microscopically beyond the basement membrane.}, } @article {pmid23466329, year = {2013}, author = {Yu, XF and Feng, WL and Miao, LL and Chen, B and Yang, HJ}, title = {The prognostic significance of molecular subtype for male breast cancer: a 10-year retrospective study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {824-827}, doi = {10.1016/j.breast.2013.02.005}, pmid = {23466329}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*chemistry ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is rare. Molecular subtype has been utilized widely in female breast cancer. But the relationship between subtype and prognosis in MBC patients is still unknown. We aim to study the impact of molecular subtype on the prognosis of MBC.

METHODS: We identified MBC cases from 1990 to 2011 retrospectively; molecular subtype was assigned by immunohistochemistry. We compared overall survival in different subtypes by Kaplan-Meier method and COX proportional hazard regression model.

RESULTS: 68 patients with MBC were included in analysis with 115 months of a median follow-up time. Comparing to non-luminal A (subtypes of Luminal B, HER2 over-express and Basal-like) group, patients with luminal A had a lower recurrent rate and better overall survival (10-year survival rate was 78.0% vs 67.0%, mean survival time 197.46 ± 12.22 months vs 146.51 ± 16.88 months, p < 0.05).

CONCLUSION: Molecular subtype may have prognosis-predicting value for MBC.}, } @article {pmid23465281, year = {2013}, author = {Oda, Y and Aishima, S and Morimatsu, K and Hayashi, A and Shindo, K and Fujino, M and Mizuuchi, Y and Hattori, M and Tanaka, M and Oda, Y}, title = {Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas.}, journal = {Human pathology}, volume = {44}, number = {8}, pages = {1487-1498}, doi = {10.1016/j.humpath.2012.12.001}, pmid = {23465281}, issn = {1532-8392}, mesh = {Adenocarcinoma, Mucinous/*metabolism/mortality/pathology ; Biomarkers, Tumor/analysis ; Carcinoma in Situ/*metabolism/mortality/pathology ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/pathology ; Carcinoma, Papillary/*metabolism/mortality/pathology ; Cytoskeletal Proteins/analysis/*biosynthesis ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Pancreatic Neoplasms/*metabolism/mortality/pathology ; Phosphorylation ; }, abstract = {Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.}, } @article {pmid23456318, year = {2013}, author = {Kulkarni, N and Pezzi, CM and Greif, JM and Suzanne Klimberg, V and Bailey, L and Korourian, S and Zuraek, M}, title = {Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base.}, journal = {Annals of surgical oncology}, volume = {20}, number = {7}, pages = {2236-2241}, doi = {10.1245/s10434-013-2911-z}, pmid = {23456318}, issn = {1534-4681}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/metabolism/*pathology/*therapy ; Carcinoma, Adenoid Cystic/metabolism/*secondary/*therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/*therapy ; Chemotherapy, Adjuvant ; Female ; Hormones/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptors, Estrogen/metabolism ; Receptors, Progesterone ; }, abstract = {BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy.

METHODS: Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003).

RESULTS: A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal.

CONCLUSIONS: Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.}, } @article {pmid23450635, year = {2013}, author = {Maeda, H and Yokoi, S and Nakazawa, M and Koneri, K and Imamura, Y and Yamaguchi, A}, title = {Adenomyoepithelial adenosis associated with breast cancer: a case report and review of the literature.}, journal = {SpringerPlus}, volume = {2}, number = {1}, pages = {50}, pmid = {23450635}, issn = {2193-1801}, abstract = {Adenomyoepithelial adenosis of the breast is an extremely rare type of adenosis. We herein present the case of a 35-year-old woman, who presented with a small painless hard lump and elastic soft induration of 5 cm in diameter in her left breast. Clinical examination and diagnostic workup were suggestive of a breast carcinoma, and a modified radical mastectomy and sentinel node biopsy were performed. Histopathological examination revealed adenomyoepithelial adenosis along with fibrocystic change and small invasive ductal carcinoma, slightly away from the adenosis. The presented case was thought to be initial-stage adenomyoepithelial adenosis and independently developing breast cancer. From a review of five reported cases of adenomyoepithelial adenosis, complete resection of the tumor and coexisting malignant disease may be recommended, owing to the tendency to develop breast cancer or malignant adenomyoepithelioma, or recurrence.}, } @article {pmid23445447, year = {2013}, author = {Duan, R and Zuo, X and Wang, S and Quan, X and Chen, D and Chen, Z and Jiang, L and Fan, C and Xia, F}, title = {Lab in a tube: ultrasensitive detection of microRNAs at the single-cell level and in breast cancer patients using quadratic isothermal amplification.}, journal = {Journal of the American Chemical Society}, volume = {135}, number = {12}, pages = {4604-4607}, doi = {10.1021/ja311313b}, pmid = {23445447}, issn = {1520-5126}, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Female ; Humans ; Limit of Detection ; MicroRNAs/*analysis/genetics ; Nucleic Acid Amplification Techniques/*methods ; }, abstract = {Through rational design of a functional molecular probe with high sequence specificity that takes advantage of sensitive isothermal amplification with simple operation, we developed a one-pot hairpin-mediated quadratic enzymatic amplification strategy for microRNA (miRNA) detection. Our method exhibits ultrahigh sensitivity toward miR-21 with detection limits of 10 fM at 37 °C and 1 aM at 4 °C, which corresponds to nine strands of miR-21 in a 15 μL sample, and it is capable of distinguishing among miRNA family members. More importantly, the proposed approach is also sensitive and selective when applied to crude extractions from MCF-7 and PC3 cell lines and even patient tissues from intraductal carcinoma and invasive ductal carcinoma of the breast.}, } @article {pmid23440416, year = {2013}, author = {Mochizuki, K and Xie, F and He, S and Tong, Q and Liu, Y and Mochizuki, I and Guo, Y and Kato, K and Yagita, H and Mineishi, S and Zhang, Y}, title = {Delta-like ligand 4 identifies a previously uncharacterized population of inflammatory dendritic cells that plays important roles in eliciting allogeneic T cell responses in mice.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {190}, number = {7}, pages = {3772-3782}, pmid = {23440416}, issn = {1550-6606}, support = {P30 CA046592/CA/NCI NIH HHS/United States ; R01 CA172106/CA/NCI NIH HHS/United States ; R01-CA-172106-01/CA/NCI NIH HHS/United States ; 5P30CA46592/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Dendritic Cells/*immunology/*metabolism ; Disease Models, Animal ; Gastrointestinal Tract/immunology/metabolism ; Gene Expression ; Gene Expression Profiling ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Interferon-gamma/biosynthesis ; Interleukin-17/biosynthesis ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Isoantigens/*immunology ; Ligands ; Lymphocyte Activation/immunology ; Membrane Proteins/genetics/*metabolism ; Mice ; Receptors, Notch/metabolism ; Spleen/immunology/metabolism ; T-Lymphocytes/*immunology ; Transplantation, Homologous/immunology ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {Graft-versus-host disease (GVHD) reflects an exaggerated inflammatory allogeneic T cell response in hosts receiving allogeneic hematopoietic stem cell transplantation (HSCT). Inhibition of pan-Notch receptor signaling in donor T cells causes reduction of GVHD. However, which Notch ligand(s) in what APCs is important for priming graft-versus-host reaction remains unknown. We demonstrate that δ-like ligand-4 (Dll4) and Dll4-positive (Dll4(high)) inflammatory dendritic cells (i-DCs) play important roles in eliciting allogeneic T cell responses. Host-type Dll4(high) i-DCs occurred in the spleen and intestine of HSCT mice during GVHD induction phase. These Dll4(high) i-DCs were CD11c(+)B220(+)PDCA-1(+), resembling plasmacytoid dentritic cells (pDCs) of naive mice. However, as compared with unstimulated pDCs, Dll4(high) i-DCs expressed higher levels of costimulatory molecules, Notch ligands Jagged1 and Jagged2, and CD11b, and produced more Ifnb and Il23 but less Il12. In contrast, Dll4-negative (Dll4(low)) i-DCs were CD11c(+)B220(-)PDCA-1(-), and had low levels of Jagged1. In vitro assays showed that Dll4(high) i-DCs induced significantly more IFN-γ- and IL-17-producing effector T cells (3- and 10-fold, respectively) than Dll4(low) i-DCs. This effect could be blocked by anti-Dll4 Ab. In vivo administration of Dll4 Ab reduced donor-alloreactive effector T cells producing IFN-γ and IL-17 in GVHD target organs, leading to reduction of GVHD and improved survival of mice after allogeneic HSCT. Our findings indicate that Dll4(high) i-DCs represent a previously uncharacterized i-DC population distinctive from steady state DCs and Dll4(low) i-DCs. Furthermore, Dll4 and Dll4(high) i-DCs may be beneficial targets for modulating allogeneic T cell responses, and could facilitate the discovery of human counterparts of mouse Dll4(high) i-DCs.}, } @article {pmid23436864, year = {2013}, author = {Jones, KN and Guimaraes, LS and Reynolds, CA and Ghosh, K and Degnim, AC and Glazebrook, KN}, title = {Invasive micropapillary carcinoma of the breast: imaging features with clinical and pathologic correlation.}, journal = {AJR. American journal of roentgenology}, volume = {200}, number = {3}, pages = {689-695}, doi = {10.2214/AJR.12.8512}, pmid = {23436864}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Papillary/*diagnosis/pathology ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Neoplasm Invasiveness ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {OBJECTIVE: The purpose of this article is to present imaging findings of invasive ductal carcinoma with micropapillary features with clinical and pathologic correlation.

MATERIALS AND METHODS: We retrospectively searched our institution's surgical pathology database for patients with pathologically proven invasive ductal carcinoma with micropapillary features. Forty-one patients with images available for review were included in the study. Mammographic, sonographic, and MRI findings were assessed using the American College of Radiology's BI-RADS lexicon. Molecular breast imaging findings were reviewed using a molecular breast imaging lexicon. Imaging findings were correlated with clinical presentation and pathologic findings.

RESULTS: Mammographically, the most common finding was an irregular spiculated mass. Sonographically, the most common finding was an irregular hypoechoic mass with spiculated margins and posterior acoustic shadowing. With MRI, the most common finding was an irregular mass with washout kinetics, but we also observed diffuse heterogeneous nonmasslike enhancement throughout the breast. Molecular breast imaging was available for one patient and showed multicentric radiotracer uptake. Analysis of 39 pathologic specimens showed 27 (69%) with angiolymphatic invasion. Axillary nodal metastases were present in 23 patients (59%), nine (23%) with extranodal extension.

CONCLUSION: The imaging features of invasive ductal carcinoma of the breast with micropapillary features typically were highly suggestive of malignancy. The malignancies were strongly associated with lymphovascular invasion and lymph node metastases. Radiologists should be aware of the imaging features of this unusual variant and should consider axillary sonography if this entity is found in a core needle biopsy specimen.}, } @article {pmid23436478, year = {2013}, author = {Pierobon, D and Bosco, MC and Blengio, F and Raggi, F and Eva, A and Filippi, M and Musso, T and Novelli, F and Cappello, P and Varesio, L and Giovarelli, M}, title = {Chronic hypoxia reprograms human immature dendritic cells by inducing a proinflammatory phenotype and TREM-1 expression.}, journal = {European journal of immunology}, volume = {43}, number = {4}, pages = {949-966}, doi = {10.1002/eji.201242709}, pmid = {23436478}, issn = {1521-4141}, mesh = {Cell Hypoxia ; Cells, Cultured ; Cytokines/*metabolism ; Dendritic Cells/*immunology/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation Mediators/*metabolism ; Membrane Glycoproteins/genetics/*metabolism ; *Phenotype ; Receptors, Immunologic/genetics/immunology/*metabolism ; Th1 Cells/immunology/metabolism ; Th17 Cells/immunology/metabolism ; Triggering Receptor Expressed on Myeloid Cells-1 ; }, abstract = {DCs are powerful antigen-presenting cells central in the orchestration of innate and acquired immunity. DC development, migration, and activities are intrinsically linked to the microenvironment. DCs migrate through pathologic tissues before reaching their final destination in the lymph nodes. Hypoxia, a condition of low partial oxygen pressure, is a common feature of many pathologic situations, capable of modifying DC phenotype and functional behavior. We studied human monocyte-derived immature DCs generated under chronic hypoxic conditions (H-iDCs). We demonstrate by gene expression profiling the upregulation of a cluster of genes coding for antigen-presentation, immunoregulatory, and pattern recognition receptors, suggesting a stimulatory role for hypoxia on iDC immunoregulatory functions. In particular, we show that H-iDCs express triggering receptor expressed on myeloid cells(TREM-1), a member of the Ig superfamily of immunoreceptors and an amplifier of inflammation. This effect is reversible because H-iDC reoxygenation results in TREM-1 down-modulation. TREM-1 engagement promotes upregulation of T-cell costimulatory molecules and homing chemokine receptors, typical of mature DCs, and increases the production of proinflammatory, Th1/Th17-priming cytokines/chemokines, resulting in increased T-cell responses. These results suggest that TREM-1 induction by the hypoxic microenvironment represents a mechanism of regulation of Th1-cell trafficking and activation by iDCs differentiated at pathologic sites.}, } @article {pmid23432978, year = {2013}, author = {Baslaim, MM and Al-Amoudi, SA and Al-Ghamdi, MA and Ashour, AS and Al-Numani, TS}, title = {Case report: Breast cancer associated with contralateral tuberculosis of axillary lymph nodes.}, journal = {World journal of surgical oncology}, volume = {11}, number = {}, pages = {43}, pmid = {23432978}, issn = {1477-7819}, mesh = {Aged ; Axilla ; Breast Neoplasms/complications/*microbiology/pathology ; Carcinoma, Ductal, Breast/complications/*microbiology/secondary ; Female ; Humans ; Lymph Nodes/*microbiology/pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Prognosis ; Tuberculosis, Lymph Node/*complications/microbiology ; }, abstract = {BACKGROUND: Breast cancer coexisting with tuberculous axillary lymph nodes is rare.

CASE REPORT: We report a 69 years old Yemeni patient with a left breast invasive ductal carcinoma associated with contralateral tuberculous axillary lymph nodes containing microcalcifications mimicking malignancy. The patient had to be investigated for the possibility of bilateral breast cancer since she had no history of previous exposure to tuberculosis.

CONCLUSION: Tuberculosis involving lymph nodes can create a diagnostic dilemma in the presence of a malignant process. The presence of calcifications in lymph nodes should raise the possibility of tuberculosis even in the absence of contact history with tuberculosis.}, } @article {pmid23421821, year = {2013}, author = {Contino, F and Mazzarella, C and Ferro, A and Lo Presti, M and Roz, E and Lupo, C and Perconti, G and Giallongo, A and Feo, S}, title = {Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {81}, pmid = {23421821}, issn = {1471-2407}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; *Genes, erbB-2 ; Histone Deacetylase 1/genetics/*metabolism ; Humans ; Immunohistochemistry ; Neoplasm Proteins/genetics/*metabolism ; Promoter Regions, Genetic ; Receptor, ErbB-2/metabolism ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far.

METHODS: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry.

RESULTS: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and -262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples.

CONCLUSIONS: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC.}, } @article {pmid23418456, year = {2013}, author = {El-Shinawi, M and Mohamed, HT and El-Ghonaimy, EA and Tantawy, M and Younis, A and Schneider, RJ and Mohamed, MM}, title = {Human cytomegalovirus infection enhances NF-κB/p65 signaling in inflammatory breast cancer patients.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e55755}, pmid = {23418456}, issn = {1932-6203}, mesh = {Adult ; Aged ; Cytomegalovirus Infections/complications/*metabolism/virology ; Female ; Gene Expression Profiling ; Humans ; Inflammatory Breast Neoplasms/complications/*metabolism/virology ; Middle Aged ; NF-kappa B/genetics/*metabolism ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Signal Transduction/*physiology ; Up-Regulation ; }, abstract = {Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (IBC), a rapidly progressing form of breast cancer characterized by specific molecular signature. We screened for anti-CMV IgG antibodies in peripheral blood of 49 non-IBC invasive ductal carcinoma (IDC) and 28 IBC patients. In addition, we screened for HCMV-DNA in postsurgical cancer and non-cancer breast tissues of non-IBC and IBC patients. We also tested whether HCMV infection can modulate the expression and activation of transcriptional factor NF-κB/p65, a hallmark of IBC. Our results reveal that IBC patients are characterized by a statistically significant increase in HCMV IgG antibody titers compared to non-IBC patients. HCMV-DNA was significantly detected in cancer tissues than in the adjacent non-carcinoma tissues of IBC and IDC, and IBC cancer tissues were significantly more infected with HCMV-DNA compared to IDC. Further, HCMV sequence analysis detected different HCMV strains in IBC patients tissues, but not in the IDC specimens. Moreover, HCMV-infected IBC cancer tissues were found to be enhanced in NF-κB/p65 signaling compared to non-IBC patients. The present results demonstrated a correlation between HCMV infection and IBC. Etiology and causality of HCMV infection with IBC now needs to be rigorously examined.}, } @article {pmid23416046, year = {2013}, author = {Dreyer, G and Vandorpe, T and Smeets, A and Forceville, K and Brouwers, B and Neven, P and Janssens, H and Deraedt, K and Moerman, P and Van Calster, B and Christiaens, MR and Paridaens, R and Wildiers, H}, title = {Triple negative breast cancer: clinical characteristics in the different histological subtypes.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {761-766}, doi = {10.1016/j.breast.2013.01.009}, pmid = {23416046}, issn = {1532-3080}, mesh = {Age Factors ; Aged ; Carcinoma/*pathology/secondary/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy ; Radiotherapy, Adjuvant ; Treatment Outcome ; Triple Negative Breast Neoplasms/*pathology/therapy ; }, abstract = {PURPOSE: To investigate the clinical behavior of triple negative breast cancer (TNC), including age distribution, occurrence of LN (lymph node) invasion and prognosis in different histological subtypes.

METHODS: For this cohort study we used data on 476 patients with newly diagnosed TNC at the University Hospitals Leuven (Belgium) between 1999 and 2009. Of these, 395 received upfront surgery, 68 neoadjuvant chemotherapy and 21 had metastases at diagnosis.

RESULTS: Apocrine and invasive lobular TNC occur more often in older patients compared to IDC-NOS. Of the primarily operated patients with TNC, 35.1% has pathological LN involvement. There were no significant differences in nodal invasion between different histological subtypes, but most subtypes contained few patients. In contrast to previous reports, 6/14 of apocrine TNC had LN involvement. Disease free survival (DFS) was different in different histological subtypes, but group sizes were insufficient to be able to draw firm conclusions. Within the histologically 'homogeneous' IDC-NOS group with primary surgery and outcome data (n = 300), DFS with 3.5 year median follow-up decreased with increasing age, but chemotherapy and radiotherapy were much less frequently given with increasing age. In multivariable analysis, lower age, presence of LN involvement, lack of administration of chemotherapy and radiotherapy were significant predictors of relapse.

CONCLUSION: TNC is not a uniform disease. Different histological subtypes have different age distribution and behavior. The prognosis of the most common histological subgroup, IDC-NOS, is better in older patients, but this is counterbalanced by significantly decreased use of chemotherapy and radiotherapy.}, } @article {pmid23415885, year = {2013}, author = {Grobmyer, SR and Lightsey, JL and Bryant, CM and Shaw, C and Yeung, A and Bhandare, N and Hitchingham, B and Copeland, EM}, title = {Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program.}, journal = {Journal of the American College of Surgeons}, volume = {216}, number = {4}, pages = {617-23; discussion 623-4}, doi = {10.1016/j.jamcollsurg.2012.12.038}, pmid = {23415885}, issn = {1879-1190}, mesh = {Aged ; Brachytherapy/*methods ; Breast Neoplasms/*radiotherapy/surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Period ; Middle Aged ; Radiotherapy Dosage ; Retrospective Studies ; }, abstract = {BACKGROUND: The Intrabeam (Carl Zeiss) brachytherapy device (IB) is an electronic brachytherapy device that can be used to deliver low energy x-rays (50 kV) to a lumpectomy cavity at the time of lumpectomy for breast cancer. Reported experience with IB for breast cancer in the United States has been extremely limited. Here we describe our experience and analyze the impact of IB on our multidisciplinary breast cancer program.

STUDY DESIGN: This is a retrospective review of a prospectively collected breast cancer database. Patient characteristics, treatment characteristics, recurrence, and cosmesis were analyzed. Cost data were also analyzed to determine the impact of IB on the breast cancer program.

RESULTS: Seventy-eight patients underwent 80 IB treatments in this series between November 2010 and October 2012. Most patients had invasive ductal carcinoma. Mean total operative time for patients receiving lumpectomy, sentinel node biopsy, and IB was 132 minutes (range 79 to 243 minutes). Intrabeam brachytherapy was the only adjuvant radiation required in 81% of patients, and only 15% of patients required additional operation after the index lumpectomy procedure. At 12 months of follow-up, cosmesis was good to excellent in 92% of patients. There have been no local recurrences in patients treated in this series. Intrabeam brachytherapy is associated with considerably lower costs ($1,857) than conventional whole breast radiation therapy ($9,653).

CONCLUSIONS: Implementation of IB impacts treatment planning and operating room use in a multidisciplinary breast cancer program. The safety profile, ease of administration, and reduced costs of IB favor its more widespread use in selected patients with early-stage breast cancer.}, } @article {pmid23412907, year = {2013}, author = {Khurana, A and Jung-Beom, D and He, X and Kim, SH and Busby, RC and Lorenzon, L and Villa, M and Baldi, A and Molina, J and Goetz, MP and Shridhar, V}, title = {Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts.}, journal = {Clinical & experimental metastasis}, volume = {30}, number = {4}, pages = {407-415}, pmid = {23412907}, issn = {1573-7276}, support = {P50 CA136393/CA/NCI NIH HHS/United States ; R01 CA106954/CA/NCI NIH HHS/United States ; R01 CA123249/CA/NCI NIH HHS/United States ; CA106954-04/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carcinoma, Lobular/drug therapy/*metabolism/secondary ; Cell Proliferation ; Extracellular Matrix/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Mice ; Neoplasm Grading ; Proteasome Inhibitors/*pharmacology ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfatases ; Sulfotransferases/antagonists & inhibitors/genetics/*metabolism ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.}, } @article {pmid23412348, year = {2013}, author = {Zhang, W and Zhang, T and Lin, Z and Zhang, X and Liu, F and Wang, Y and Liu, H and Yang, Y and Niu, Y}, title = {Invasive cribriform carcinoma in a Chinese population: comparison with low-grade invasive ductal carcinoma-not otherwise specified.}, journal = {International journal of clinical and experimental pathology}, volume = {6}, number = {3}, pages = {445-457}, pmid = {23412348}, issn = {1936-2625}, mesh = {Adult ; Aged ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Cell Proliferation ; China ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {Invasive cribriform carcinoma (ICC) and low-grade invasive ductal carcinoma (IDC) were recently considered to belong to a low-grade breast neoplasia family. However, none of publications has compared ICC and low-grade IDC at present. Meanwhile, in order to evaluate prognostic significance of clinicopathological characteristics of different cribriform contents in ICC and invasive breast cancer with less cribriform structures, a retrospective review of fifty-one cases of ICC and forty cases of invasive breast cancer with less cribriform pattern (less than fifty percent) was conducted in a Chinese population. Forty-nine cases of low-grade IDC without cribriform elements were selected as a control. ICC presented more favorable prognostic factors than those of invasive breast carcinoma with less cribriform pattern and low-grade IDC, such as smaller tumor size, less frequent axillary lymph node involvement, higher positive rate of estrogen receptor and/or progestogen receptor expression, and lower proliferation index. The expression of human epidermal growth factor receptor two in ICC and invasive breast cancer with less cribriform pattern was mostly negative. Pure ICC showed less frequency of axillary lymph node involvement, but not its number. The proliferation index in the pure type was lower, although the tumor size in these two types was not obviously different. Tumors contained cribriform structures had a more favorable prognosis than those with low-grade IDC. Considering the tumor biology, and the benign course of pure ICC studied, chemotherapy may not be indicated in the typical case.}, } @article {pmid23406456, year = {2013}, author = {Erro, R and Barone, P and Moccia, M and Amboni, M and Vitale, C}, title = {Abnormal eating behaviors in progressive supranuclear palsy.}, journal = {European journal of neurology}, volume = {20}, number = {3}, pages = {e47-e48}, doi = {10.1111/ene.12077}, pmid = {23406456}, issn = {1468-1331}, mesh = {Aged ; *Feeding Behavior ; Feeding and Eating Disorders/*etiology ; Humans ; Middle Aged ; Supranuclear Palsy, Progressive/*complications ; }, } @article {pmid23406155, year = {2013}, author = {Dupont, E and Gomez, J and Bilodeau, D}, title = {Beyond UV radiation: a skin under challenge.}, journal = {International journal of cosmetic science}, volume = {35}, number = {3}, pages = {224-232}, doi = {10.1111/ics.12036}, pmid = {23406155}, issn = {1468-2494}, mesh = {Humans ; Infrared Rays ; Life Style ; Skin/drug effects/*radiation effects ; Sunscreening Agents/pharmacology ; *Ultraviolet Rays ; }, abstract = {Since ancient times, human beings have been trying to protect their skin against the adverse effects of the sun. From the first mineral sunscreens used by Egyptians, to the current more sophisticated ultraviolet (UVA/UVB) organic sunscreens, progress has been made in terms of sun protection and deeper knowledge of skin physiology has been acquired in the process. The solar spectrum is composed of radiations of various wavelengths having specific, as well as overlapping effects on skin. UVB is mainly responsible for sunburn and DNA dimer formation that can lead to mutation. UVA generates oxidative reactions affecting DNA, proteins and lipids, and is also immunosuppressive. Recently, visible light and infrared radiation (IR) have been associated with oxidative damage and IR has been additionally linked to adverse heat effects on skin. Numerous other extrinsic factors, related to environment and lifestyle, also affect the appearance of skin, precipitating ageing. New molecular mechanisms linking sun and environmental factors to skin ageing have been identified: IR affects mitochondrial integrity and specific heat receptors also mediate some of its effects, tryptophan is a chromophore for UVB, and the aryl hydrocarbon receptor (AhR) is activated by light and xenobiotics to alter skin physiology. Integrating all these new elements is changing the way we think about skin extrinsic ageing. Is UVA/UVB sunscreen protection still enough for our skin?}, } @article {pmid23404186, year = {2013}, author = {Philippin-Lauridant, G and Baranzelli, MC and Samson, C and Fournier, C and Pinte, S and Mattot, V and Bonneterre, J and Soncin, F}, title = {Expression of Egfl7 correlates with low-grade invasive lesions in human breast cancer.}, journal = {International journal of oncology}, volume = {42}, number = {4}, pages = {1367-1375}, doi = {10.3892/ijo.2013.1820}, pmid = {23404186}, issn = {1791-2423}, mesh = {3T3 Cells ; Adult ; Aged ; Aged, 80 and over ; Animals ; Axilla/pathology ; Breast Neoplasms/metabolism/mortality/pathology ; Breast Neoplasms, Male/*metabolism/mortality/pathology ; Calcium-Binding Proteins ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/secondary ; Carcinoma, Lobular/*metabolism/mortality/secondary ; Cells, Cultured ; Disease-Free Survival ; EGF Family of Proteins ; Endothelial Growth Factors/genetics/*metabolism ; Female ; Gene Expression ; Human Umbilical Vein Endothelial Cells ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness ; Organ Specificity ; }, abstract = {Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.}, } @article {pmid23399982, year = {2013}, author = {Valencia, JF and Vallverdú, M and Porta, A and Voss, A and Schroeder, R and Vázquez, R and Bayés de Luna, A and Caminal, P}, title = {Ischemic risk stratification by means of multivariate analysis of the heart rate variability.}, journal = {Physiological measurement}, volume = {34}, number = {3}, pages = {325-338}, doi = {10.1088/0967-3334/34/3/325}, pmid = {23399982}, issn = {1361-6579}, mesh = {Cardiomyopathy, Dilated/physiopathology ; Discriminant Analysis ; Entropy ; Female ; Heart Rate/*physiology ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Ischemia/*physiopathology ; Proportional Hazards Models ; Regression Analysis ; Risk Assessment/*methods ; }, abstract = {In this work, a univariate and multivariate statistical analysis of indexes derived from heart rate variability (HRV) was conducted to stratify patients with ischemic dilated cardiomyopathy (IDC) in cardiac risk groups. Indexes conditional entropy, refined multiscale entropy (RMSE), detrended fluctuation analysis, time and frequency analysis, were applied to the RR interval series (beat-to-beat series), for single and multiscale complexity analysis of the HRV in IDC patients. Also, clinical parameters were considered. Two different end-points after a follow-up of three years were considered: (i) analysis A, with 151 survivor patients as a low risk group and 13 patients that suffered sudden cardiac death as a high risk group; (ii) analysis B, with 192 survivor patients as a low risk group and 30 patients that suffered cardiac mortality as a high risk group. A univariate and multivariate linear discriminant analysis was used as a statistical technique for classifying patients in risk groups. Sensitivity (Sen) and specificity (Spe) were calculated as diagnostic criteria in order to evaluate the performance of the indexes and their linear combinations. Sen and Spe values of 80.0% and 72.9%, respectively, were obtained during daytime by combining one clinical parameter and one index from RMSE, and during nighttime Sen = 80% and Spe = 73.4% were attained by combining one clinical factor and two indexes from RMSE. In particular, relatively long time scales were more relevant for classifying patients into risk groups during nighttime, while during daytime shorter scales performed better. The results suggest that the left atrial size, indexed to body surface and RMSE indexes are those that allow enhanced classification of ischemic patients in their respective risk groups, confirming that a single measurement is not enough to fully characterize ischemic risk patients and the clinical relevance of HRV complexity measures.}, } @article {pmid23399321, year = {2013}, author = {Li, S and Meng, H and Zhou, F and Zhai, L and Zhang, L and Gu, F and Fan, Y and Lang, R and Fu, L and Gu, L and Qi, L}, title = {MicroRNA-132 is frequently down-regulated in ductal carcinoma in situ (DCIS) of breast and acts as a tumor suppressor by inhibiting cell proliferation.}, journal = {Pathology, research and practice}, volume = {209}, number = {3}, pages = {179-183}, doi = {10.1016/j.prp.2012.12.002}, pmid = {23399321}, issn = {1618-0631}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics ; Cell Proliferation ; Down-Regulation ; Female ; *Genes, Tumor Suppressor ; Humans ; MicroRNAs/*genetics ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer. The currently accepted step-wise model suggests that breast cancer progressed in the following manner: normal breast cell→usually ductal hyperplasia (UDH)→atypical ductal hyperplasia (ADH)→DCIS→invasive ductal carcinoma (IDC). Therefore, DCIS can serve as a good model to analyze the mechanism underlying invasive breast cancer occurrence. MicroRNAs (miRNAs) are a novel class of small non-coding RNAs (~22nt) involved in the regulation of various biological processes. Altered miRNA expression could also contribute to the origination of cancer, including breast cancer. Here, by using miRNA microarray and real time PCR, we analyzed the miRNA expression profile in 21 DCIS and the corresponding normal tissues. miR-10b, miR-125b, miR-132, miR-145, miR-154-3p, miR-382-5p and miR-409-3p were found to be significantly deregulated in DCIS. Results from CCK-8 assay showed that the overexpression of miR-132 could inhibit the proliferation of breast cancer cell line. High expression of miR-132 could also inhibit the colony formation. Our findings will lead to further understanding of the development of breast cancer.}, } @article {pmid23394449, year = {2012}, author = {Omran, OM}, title = {The prognostic value of breast cancer resistance protein (BCRB/ABCG2) expression in breast carcinomas.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {31}, number = {4}, pages = {367-376}, doi = {10.1615/jenvironpatholtoxicoloncol.2013006767}, pmid = {23394449}, issn = {2162-6537}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/analysis/*metabolism ; Adult ; Aged ; Breast Neoplasms/*diagnosis/*metabolism/mortality ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*metabolism/mortality ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/analysis/*metabolism ; Prognosis ; Receptor, ErbB-2/analysis/*metabolism ; Receptors, Estrogen/analysis/metabolism ; }, abstract = {In cancer, the level of expression of breast cancer resistance protein (BCRP/ABCG2) can vary depending on cell type. However, its precise role in breast cancer has been controversial. The aim of this study was to investigate the expression of ABCG2 in breast carcinomas and relate the results to the established prognostic factors. An immunohistochemical study was conducted on 200 breast carcinoma specimens using the avidin-biotin peroxidase method. ABCG2 was expressed in 77% of cases of invasive ductal carcinoma. There was a statistically significant correlation between ABCG2 expression and each of the tumor grade, clinical stage, lymph node metastasis, and HER2 immunostaining, but no such association with progesterone receptor (PR) and estrogen receptor (ER) status. Increased expression of ABCG2 in invasive ductal carcinoma cells and its statistically significant correlation with HER2 expression are strongly correlated with tumor progression, invasion, and metastasis in human breast cancer and indicates that ABCG2 can be used as a target for the development of novel therapies.}, } @article {pmid23389824, year = {2013}, author = {Rovner, E and Dmochowski, R and Chapple, C and Thompson, C and Lam, W and Haag-Molkenteller, C}, title = {OnabotulinumtoxinA improves urodynamic outcomes in patients with neurogenic detrusor overactivity.}, journal = {Neurourology and urodynamics}, volume = {32}, number = {8}, pages = {1109-1115}, doi = {10.1002/nau.22376}, pmid = {23389824}, issn = {1520-6777}, mesh = {Adult ; Aged ; Botulinum Toxins, Type A/pharmacology/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/complications/*physiopathology ; Neuromuscular Agents/pharmacology/*therapeutic use ; Quality of Life ; Spinal Cord Injuries/complications/*physiopathology ; Treatment Outcome ; Urinary Bladder, Neurogenic/*drug therapy/etiology/physiopathology ; Urinary Bladder, Overactive/*drug therapy/etiology/physiopathology ; Urodynamics/*drug effects/physiology ; }, abstract = {AIMS: To evaluate the effect of onabotulinumtoxinA on urodynamic outcomes in patients with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

METHODS: Results from two pivotal Phase III trials (n = 691) were pooled. MS or SCI patients with NDO, received intradetrusor onabotulinumtoxinA 200 U (n = 227), 300 U (n = 223), or placebo (n = 241). Change from baseline in UI episodes/week (Week 6), maximum cystometric capacity (MCC), maximum detrusor pressure at first involuntary detrusor contraction (IDC) (PdetmaxIDC), volume at first IDC (VpmaxIDC), and detrusor compliance (DC) were measured.

RESULTS: OnabotulinumtoxinA significantly increased MCC overall (+153.6 ml with 200 U vs. +11.9 ml with placebo). Over 60% of onabotulinumtoxinA-treated patients had no IDC at Week 6; in patients with an IDC at Week 6, VpmaxIDC improved (+183.4 ml with 200 U vs. +17.5 ml with placebo), and PdetmaxIDC decreased (-32.4 cmH2O with 200 U vs. +1.1 cmH2O with placebo). OnabotulinumtoxinA-treated patients had a significant increase in DC (+59.8 ml/cmH2O with 200 U vs. -5.2 with placebo). Urodynamic improvements were comparable in patients regardless of baseline DC and corresponded with significant reductions in UI episodes/week for both onabotulinumtoxinA doses versus placebo, with no clinically relevant differences between 200 and 300 U groups. Most common adverse event was urinary tract infection (UTI); complicated UTIs were low across all treatment groups. In patients not catheterizing at baseline, a dose-dependent increase in post-void residual urine was observed at Week 2 following onabotulinumtoxinA treatment.

CONCLUSIONS: OnabotulinumtoxinA significantly improved urodynamic outcomes in NDO patients, even in those with low baseline DC, and corresponded with improvements in UI episodes. Both doses of onabotulinumtoxinA were well tolerated.}, } @article {pmid23380883, year = {2014}, author = {Naveh, E and Katz-Navon, T}, title = {Antecedents of willingness to report medical treatment errors in health care organizations: a multilevel theoretical framework.}, journal = {Health care management review}, volume = {39}, number = {1}, pages = {21-30}, doi = {10.1097/HMR.0b013e3182862869}, pmid = {23380883}, issn = {1550-5030}, mesh = {Attitude of Health Personnel ; *Delivery of Health Care/organization & administration ; *Disclosure ; Health Personnel/*psychology ; Humans ; Medical Errors/*psychology ; Models, Organizational ; Organizational Culture ; Patient Safety ; }, abstract = {BACKGROUND: To avoid errors and improve patient safety and quality of care, health care organizations need to identify the sources of failures and facilitate implementation of corrective actions. Hence, health care organizations try to collect reports and data about errors by investing enormous resources in reporting systems. However, despite health care organizations' declared goal of increasing the voluntary reporting of errors and although the Patient Safety and Quality Improvement Act of 2005 (S.544, Public Law 109-41) legalizes efforts to secure reporters from specific liabilities, the problem of underreporting of adverse events by staff members remains.

PURPOSE: The purpose of the paper is to develop a theory-based model and a set of propositions to understand the antecedents of staff members' willingness to report errors based on a literature synthesis. The model aims to explore a complex system of considerations employees use when deciding whether to report their errors or be silent about them. The model integrates the influences of three types of organizational climates (psychological safety, psychological contracts, and safety climate) and individual perceptions of the applicability of the organization's procedures and proposes their mutual influence on willingness to report errors and, as a consequence, patient safety.

PRACTICE IMPLICATIONS: The model suggests that managers should try to control and influence both the way employees perceive procedure applicability and organizational context-i.e., psychological safety, no-blame contracts, and safety climate-to increase reporting and improve patient safety.}, } @article {pmid23374550, year = {2013}, author = {Tan, JZ and Waugh, J and Kumar, B and Evans, J}, title = {Mucinous carcinomas of the breast: imaging features and potential for misdiagnosis.}, journal = {Journal of medical imaging and radiation oncology}, volume = {57}, number = {1}, pages = {25-31}, doi = {10.1111/1754-9485.12006}, pmid = {23374550}, issn = {1754-9485}, mesh = {Adenocarcinoma, Mucinous/*diagnosis ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis ; Calcinosis/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diagnosis, Differential ; Diagnostic Errors/*prevention & control ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Pure mucinous breast carcinomas (PMBC) are commonly lobulated, therefore appear relatively benign compared with the imaging features of invasive ductal carcinoma. The aim of this study was to determine mammographic and sonographic patterns of PMBC, in particular features that may result in misdiagnosis.

METHODS: Retrospective review of available mammography and sonography in 90 patients diagnosed with PMBC within the Monash BreastScreen service, 1993-2011 inclusive.

RESULTS: PMBC commonly have indistinct or lobulated mammographic and sonographic margins. Mammographic calcifications are absent in the majority (82%). On ultrasound, these neoplasms are commonly isoechoic (51%) with normal posterior acoustic appearances (80%). However, most (77%) of these lesions have suspicious or definite imaging features of malignancy.

CONCLUSION: PMBC are commonly lobulated with homogeneous, isoechoic and normal posterior acoustic sonographic appearances but rarely have benign imaging features.}, } @article {pmid23374397, year = {2013}, author = {Ripamonti, CB and Colombo, M and Mondini, P and Siranoush, M and Peissel, B and Bernard, L and Radice, P and Carcangiu, ML}, title = {First description of an acinic cell carcinoma of the breast in a BRCA1 mutation carrier: a case report.}, journal = {BMC cancer}, volume = {13}, number = {}, pages = {46}, pmid = {23374397}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/surgery ; Carcinoma, Acinar Cell/*genetics/metabolism/surgery ; Carcinoma, Ductal, Breast/*genetics/surgery ; Female ; *Genes, BRCA1 ; Heterozygote ; Humans ; Mutation ; Neoplasms, Second Primary/*genetics/surgery ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/genetics ; }, abstract = {BACKGROUND: Acinic cell carcinoma (ACC) is a rare malignant epithelial neoplasm characterized by the presence of malignant tubular acinar exocrine gland structures. Diagnosis is generally made in salivary glands and in the pancreas. ACC of the breast has been reported in few cases only. Carriers of inherited mutations in the BRCA1 gene are prone to the development of breast cancer, mainly invasive ductal or medullary type carcinomas. We describe for the first time a BRCA1 mutation carrier with a diagnosis of ACC of the breast.

CASE PRESENTATION: The patient developed an invasive ductal carcinoma (IDC) at the age of 40 years and an ACC in the contralateral breast at 44 years. Immunohistochemical examination of the ACC revealed a triple negative status (i.e., negativity for estrogen receptor, progesterone receptor and HER2 protein) and positivity for p53. Using a combination of loss of heterozygosity (LOH) and sequencing analyses, the loss of the wild-type BRCA1 allele was detected in both the ACC and the IDC. In addition, two different somatic TP53 mutations, one in the ACC only and another one in the IDC only, were observed.

CONCLUSION: Both the immunohistochemical and molecular features observed in the ACC are typical of BRCA1-associated breast cancers and suggest an involvement of the patient's germline mutation in the disease. The occurrence of rare histological types of breast cancers, including malignant phyllodes tumor, atypical medullary carcinoma and metaplastic carcinoma, in BRCA1 mutation carriers has been already reported. Our findings further broaden the spectrum of BRCA1-associated breast malignancies.}, } @article {pmid23372687, year = {2013}, author = {Chen, L and Li, Y and Fu, Y and Peng, J and Mo, MH and Stamatakos, M and Teal, CB and Brem, RF and Stojadinovic, A and Grinkemeyer, M and McCaffrey, TA and Man, YG and Fu, SW}, title = {Role of deregulated microRNAs in breast cancer progression using FFPE tissue.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e54213}, pmid = {23372687}, issn = {1932-6203}, support = {R21 CA159103/CA/NCI NIH HHS/United States ; R21CA159103/CA/NCI NIH HHS/United States ; }, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Disease Progression ; Female ; Formaldehyde ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia/diagnosis/*genetics/metabolism/pathology ; MicroRNAs/*genetics/metabolism ; Neoplasm Proteins/*genetics/metabolism ; Neoplasm Staging ; Paraffin Embedding ; Tissue Fixation ; }, abstract = {MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.}, } @article {pmid23372178, year = {2013}, author = {Cooper, CL and Karim, RZ and Selinger, C and Carmalt, H and Lee, CS and O'Toole, SA}, title = {Molecular alterations in metaplastic breast carcinoma.}, journal = {Journal of clinical pathology}, volume = {66}, number = {6}, pages = {522-528}, doi = {10.1136/jclinpath-2012-201086}, pmid = {23372178}, issn = {1472-4146}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Carcinoma/genetics/*metabolism/pathology/therapy ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Metaplasia ; Neoplastic Stem Cells/metabolism/pathology ; Signal Transduction ; }, abstract = {Metaplastic carcinoma of the breast is a rare and heterogeneous subtype of breast carcinoma with a generally poor outcome, and few therapeutic options once disease recurs or progresses. Metaplastic carcinomas of the breast are usually of a larger size at diagnosis, with less frequent nodal metastasis compared with invasive ductal carcinoma no special type, and lack hormone and HER2 receptor expression. Recent research has revealed some potentially actionable genetic changes in a subset of these rare tumours. However, ongoing efforts to further characterise the genetic basis and the molecular alterations underlying the distinctive morphological and clinical characteristics of these tumours are needed in order to identify new targets for treatment. This review will describe the theories of pathogenesis of metaplastic breast carcinoma, and highlight genetic changes and potential therapeutic targets in this generally poor prognosis malignancy.}, } @article {pmid23371253, year = {2013}, author = {Zhao, H and Yang, M and Zhao, J and Wang, J and Zhang, Y and Zhang, Q}, title = {High expression of LC3B is associated with progression and poor outcome in triple-negative breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {30}, number = {1}, pages = {475}, pmid = {23371253}, issn = {1559-131X}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma in Situ/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Microtubule-associated protein 1 light chain 3B (LC3B) was involved in autophagosome formation and had been as a marker of autophagy which played an important role in the development of breast cancer. The purpose of this study was to explore the level of LC3B expression in four stages of triple-negative breast cancer (TNBC) and to evaluate the prognostic significance of LC3B expression in TNBC. The ultimate aim was to identify the new factor that could be useful in predicting clinical behavior of TNBC. We evaluated the expression level of LC3B protein in four kinds of TNBC tissue samples, including intraductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) without metastases, IDC with lymph node metastases (LNM), and IDC with distant metastases (DM). Hundred and four primary TNBC patients were involved in present study, and the expression level of LC3B protein was assessed by immunohistochemistry. Medical records of these patients were reviewed, and the clinicopathological analysis was performed. High expression of LC3B was observed in 7.7 % of DCIS (1 of 13 cases), 16.2 % of IDC (6 of 37 cases), 35.7 % of LNM (15 of 42 cases), and 58.3 % of DM (7 of 12 cases). LC3B high expression was significantly associated with tumor size (P = 0.028), lymph node metastasis (P = 0.002), and Ki-67 expression (P = 0.047). LC3B high expression patients showed poorer DFS and OS rates compared with LC3B low expression patients (P = 0.024, and P = 0.047, respectively). Multivariate analyses confirmed that high LC3B expression was an independent and significant factor for predicting the poor outcome of TNBC patients. These preliminary results demonstrated that high LC3B expression was associated with lymph node and distant metastasis. Furthermore, high LC3B protein expression was correlated with shorter survival in patients with triple-negative breast carcinoma. These findings provided preliminary evidence for the function of LC3B on the progression of TNBC and suggested LC3B was a useful marker in prognostic evaluation for patients with TNBC.}, } @article {pmid23363467, year = {2013}, author = {Holtick, U and Wang, XN and Marshall, SR and Scheid, C and von Bergwelt-Baildon, M and Dickinson, AM}, title = {Immature DC isolated after co-culture with PUVA-treated peripheral blood mononuclear cells downregulate graft-versus-host reactions in the human skin explant model.}, journal = {Current stem cell research & therapy}, volume = {8}, number = {4}, pages = {324-332}, doi = {10.2174/1574888x11308040008}, pmid = {23363467}, issn = {2212-3946}, mesh = {Cells, Cultured ; Coculture Techniques ; Dendritic Cells/*physiology ; Ficusin/*pharmacology ; Graft vs Host Disease/immunology/*prevention & control ; *Graft vs Host Reaction ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppression Therapy ; Interferon-gamma/metabolism ; Interleukin-6/metabolism ; Lymphocytes/physiology ; Photopheresis ; Photosensitizing Agents/*pharmacology ; Skin/immunology/metabolism ; Transplantation, Homologous ; }, abstract = {Graft-versus-host disease (GvHD) remains the major barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) is a potent immunomodulatory treatment option for GvHD. In contrast to conventional immunosuppressants, ECP is considered not to increase relapse and infection rates resulting from generalised immunosuppression. ECP involves the mechanical separation of 5-10% of patient peripheral blood mononuclear cells, which are then exposed to psoralen and UVA light (PUVA) before they are returned to the patient. ECP has been shown to induce apoptosis in various cell types, in particular lymphocytes. Several studies describe downregulation of pro-inflammatory cytokines as well as promotion of peripheral tolerance through enhanced production of T regulatory cells in the course of ECP-treatment. Modulation of antigen-presenting cells such as dendritic cells (DC) by PUVA-treated lymphocytes might be implicated in these regulatory processes. We evaluated the impact of PUVA-treated lymphocytes on immature DC and further demonstrated the functional capacity of such modified DC to modulate GVH reactions using a well-established human skin-explant model of GvHD. Addition of immature DC isolated after co-culture with PUVA-treated but not untreated MLR cells significantly downregulated skin-GvH reactions (p=0.023, Mann-Whitney-Test). IFN-gamma levels were non-significantly decreased in MLR and skin supernatants. We observed a non-significant increase in PD-L1 expression in iDC after co-culture with PUVA-treated MLR cells whereas expression levels of IDO and ILT-3 were not affected. We conclude that iDC modulated by PUVA-induced apoptotic cells potently downregulate allogeneic immune responses possibly through PD-L1- dependent signaling.}, } @article {pmid23361892, year = {2013}, author = {Vanderwalde, NA and Jones, EL and Kimple, RJ and Moore, DT and Klauber-Demore, N and Sartor, CI and Ollila, DW}, title = {Phase 2 study of pre-excision single-dose intraoperative radiation therapy for early-stage breast cancers: six-year update with application of the ASTRO accelerated partial breast irradiation consensus statement criteria.}, journal = {Cancer}, volume = {119}, number = {9}, pages = {1736-1743}, pmid = {23361892}, issn = {1097-0142}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; T32 GM008716/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; Intraoperative Care ; Middle Aged ; }, abstract = {BACKGROUND: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer.

METHODS: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method.

RESULTS: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%.

CONCLUSIONS: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers.}, } @article {pmid23360631, year = {2013}, author = {Dabiri, S and Talebi, A and Shahryari, J and Meymandi, MS and Safizadeh, H}, title = {Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.}, journal = {Archives of Iranian medicine}, volume = {16}, number = {2}, pages = {93-99}, pmid = {23360631}, issn = {1735-3947}, mesh = {Adult ; Aged ; Antigens, CD34/biosynthesis ; Breast/anatomy & histology/blood supply/metabolism/pathology ; Breast Neoplasms/blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*pathology ; Female ; Humans ; Microvessels/anatomy & histology/pathology ; Middle Aged ; Myofibroblasts/pathology ; Neovascularization, Pathologic/pathology ; Receptor, ErbB-2/biosynthesis ; }, abstract = {BACKGROUND: This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression.

METHODS: 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue. 

RESULTS: There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001).  MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001). 

CONCLUSION: Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts in stroma of tumor; probably may be a worse prognostic factor  and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression.}, } @article {pmid23359864, year = {2013}, author = {Khurana, A and Beleford, D and He, X and Chien, J and Shridhar, V}, title = {Role of heparan sulfatases in ovarian and breast cancer.}, journal = {American journal of cancer research}, volume = {3}, number = {1}, pages = {34-45}, pmid = {23359864}, issn = {2156-6976}, support = {R01 CA106954/CA/NCI NIH HHS/United States ; T32 CA148073/CA/NCI NIH HHS/United States ; }, abstract = {Endosulfatases HSulf-1 and -2 (also referred to as Sulf1 and -2) represent a family of enzymes that modulate heparin binding growth factor signaling. Heparan sulfatase 1 (HSulf-1) and heparan sulfatase 2 (HSulf-2) are two important 6-O endosulfatases which remove or edit 6-O sulfate residues of N-glucosamine present on highly sulfated HS. Alteration of heparan sulfatases have been identified in the context of several cancer types. Many cancer types either exhibit increased or decreased HSulfs expression at the transcript levels. Specifically, HSulf-1 was found to be downregulated in early-stage ovarian tumors, hepatocellular carcinoma, and metastatic breast cancer patients. HSulf-2 was found to be upregulated in ductal carcinoma in situ and invasive ductal carcinoma, whereas limited information is present about HSulf-2 expression in different stages of ovarian cancers. Here, we review the important role of these sulfatases play in ovarian and breast cancers in terms of tumorigenesis such as angiogenesis, chemoresistance, apoptosis, growth factor signaling, hypoxia and metastasis. These recent discoveries have added significant understanding about these sulfate editing enzymes.}, } @article {pmid23354842, year = {2013}, author = {Yamashita, N and Tokunaga, E and Kitao, H and Hisamatsu, Y and Taketani, K and Akiyoshi, S and Okada, S and Aishima, S and Morita, M and Maehara, Y}, title = {Vimentin as a poor prognostic factor for triple-negative breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {139}, number = {5}, pages = {739-746}, pmid = {23354842}, issn = {1432-1335}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/mortality/pathology ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Vimentin/*genetics/metabolism ; }, abstract = {PURPOSE: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, is a highly heterogeneous disease. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin, one of the most major factors associated with EMT was investigated in TNBC.

MATERIALS AND METHODS: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14 %) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry.

RESULTS: The mRNA expression of vimentin was significantly upregulated in the basal-type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p = 0.0042) in TNBC compared with the other subtypes. Vimentin expression was associated with a younger age (p = 0.016), high nuclear grade (p = 0.023) and high Ki67 expression (p < 0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p = 0.0058) and overall survival (OS) (p = 0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p = 0.043). Vimentin expression was also associated with a significantly shorter RFS (p = 0.021) and OS (p = 0.017) in patients with basal-like breast cancer (BLBC).

CONCLUSIONS: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.}, } @article {pmid23353551, year = {2013}, author = {Chaturbhuj, DN and Deshmukh, PS and Hingankar, NK and Siddhaarth, K and Deshpande, SN and Sen, S and Kabra, S and Paranjape, RS and Tripathy, SP}, title = {Evaluations of an in-house drug resistance method for HIV-1 drug resistance using ViroSeq™ 2.0 genotyping system as a gold standard.}, journal = {Journal of virological methods}, volume = {189}, number = {1}, pages = {87-92}, doi = {10.1016/j.jviromet.2013.01.001}, pmid = {23353551}, issn = {1879-0984}, mesh = {Anti-HIV Agents/pharmacology ; Base Sequence ; Drug Resistance, Viral/*genetics ; Genotype ; HIV Infections/*drug therapy/virology ; HIV Reverse Transcriptase/genetics ; HIV-1/*drug effects/*genetics ; Humans ; Mutation ; Peptide Hydrolases/genetics ; Sequence Analysis, DNA ; }, abstract = {An in-house method was evaluated for its efficiency to detect the HIV-1 drug resistance mutations. This method was compared with the ViroSeq™ Genotyping System 2.0 (Celera Diagnostics, US) a gold standard. Sixty-five stored plasma samples, previously tested for HIV-1 drug resistance using the ViroSeq™ method were used to evaluate the in-house method. Out of the sixty five plasma samples, sixty were HIV-1 positive clinical samples; four samples from the Virology Quality Assessment (VQA) program and one positive control from the ViroSeq™ kit were used in this study. The sequences generated by the ViroSeq™ and an in-house method showed 99.5±0.5% and 99.7±0.4% (mean±SD) nucleotide and amino acid identity, respectively. Out of 214 Stanford HIVdb listed HIV-1 drug resistance mutations in the protease and reverse transcriptase regions, concordance was observed in 203 (94.9%), partial discordance in 11 (5.1%) and complete discordance was absent. The in-house primers are broadly sensitive in genotyping multiple HIV-1 group M subtypes. The amplification sensitivity of the in-house method was 1000 copies/ml. The evaluation of the in-house method provides results comparable with that of ViroSeq™ method thus, making the in-house method suitable for HIV-1 drug resistance testing in the developing countries.}, } @article {pmid23352319, year = {2013}, author = {Trovo, M and Roncadin, M and Polesel, J and Piccoli, E and Mileto, M and Micheli, E and Perin, T and Carbone, A and Massarut, S and Trovo, MG}, title = {Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {5}, pages = {744-747}, doi = {10.1016/j.breast.2012.12.012}, pmid = {23352319}, issn = {1532-3080}, mesh = {Aged ; Aged, 80 and over ; Breast/*pathology/*radiation effects/surgery ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; *Dose Fractionation, Radiation ; Erythema/etiology ; Female ; Fibrosis/etiology ; Humans ; Mastectomy, Segmental ; Middle Aged ; Pain/etiology ; Radiotherapy, Adjuvant/adverse effects/methods ; }, abstract = {PURPOSE: To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction).

METHODS AND MATERIALS: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma.

RESULTS: 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively.

CONCLUSIONS: 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.}, } @article {pmid23347178, year = {2013}, author = {Rakha, EA and Teoh, TK and Lee, AH and Nolan, CC and Ellis, IO and Green, AR}, title = {Further evidence that E-cadherin is not a tumour suppressor gene in invasive ductal carcinoma of the breast: an immunohistochemical study.}, journal = {Histopathology}, volume = {62}, number = {5}, pages = {695-701}, doi = {10.1111/his.12066}, pmid = {23347178}, issn = {1365-2559}, mesh = {Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; Cell Membrane/metabolism/pathology ; Female ; *Genes, Tumor Suppressor ; Humans ; Multiprotein Complexes/genetics/metabolism ; Neoplasm Staging ; beta Catenin/genetics/metabolism ; }, abstract = {AIMS: E-cadherin is a cell adhesion molecule expressed in normal breast tissue; it is used generally as a phenotypical marker in breast cancer, with the absence of its expression observed frequently in lobular tumours. We have reported E-cadherin expression previously in 1516 ductal breast carcinoma using tissue microarray (TMA), where 7% of cases showed a complete absence of membrane staining. In this study, we investigated further the existence of E-cadherin-negative ductal carcinoma and evaluated the status of the E-cadherin-catenin complex in this subgroup.

MATERIAL AND METHODS: Full-face sections from excision specimens of 72 ductal breast carcinomas reported previously as E-cadherin-negative were assessed morphologically using haematoxylin and eosin staining, and immunohistochemically using two E-cadherin antibodies (HECD-1 and CDH1/4A2C7) and antibodies recognizing β-catenin and p120 proteins. Only membrane expression was considered.

RESULTS: Forty-seven ductal carcinomas were assessed after the exclusion of inappropriate cases; 34 of these showed positive E-cadherin (HECD-1) membrane expression which was focal and weak and seen mainly in invasion fronts. Ten cases showed E-cadherin (4A2C7) staining. Staining for p120 and β-catenin showed membrane staining in all cases for both antibodies, which was variable in both intensity and the proportion of positive cells.

CONCLUSION: These results demonstrate that E-cadherin-negative ductal carcinoma is rare, and in these cases p120 and β-catenin maintained their membranous localization, suggesting a functional E-cadherin-membrane complex.}, } @article {pmid23341813, year = {2012}, author = {Montero, A and Glück, S}, title = {Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer.}, journal = {Case reports in oncology}, volume = {5}, number = {3}, pages = {687-692}, pmid = {23341813}, issn = {1662-6575}, abstract = {This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triple-negative metastatic breast cancer.}, } @article {pmid23341385, year = {2013}, author = {Zhou, J and Zhan, W and Chang, C and Zhang, J and Yang, Z and Dong, Y and Zhou, C and Song, Y}, title = {Role of acoustic shear wave velocity measurement in characterization of breast lesions.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {32}, number = {2}, pages = {285-294}, doi = {10.7863/jum.2013.32.2.285}, pmid = {23341385}, issn = {1550-9613}, mesh = {Adipose Tissue/*diagnostic imaging/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Diseases/*diagnostic imaging/pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Carcinoma/diagnostic imaging/pathology ; Carcinoma, Ductal/diagnostic imaging/pathology ; Diagnosis, Differential ; Elasticity ; *Elasticity Imaging Techniques ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVES: To analyze the value of acoustic radiation force impulse imaging quantification in characterization of breast lesions and to analyze the stiffness of glandular and subcutaneous fatty tissue in benign and malignant lesions.

METHODS: A total of 175 breast lesions (67 malignant and 108 benign) in 173 women were studied. With acoustic radiation force impulse imaging, shear wave velocity (SWV), which can reflect the stiffness of tissue, was measured within the lesion (internal SWV [SWVi]), in the boundary zone (boundary SWV [SWVb]), in normal-appearing glandular tissue (glandular SWV [SWVg]), and in subcutaneous fatty tissue (fatty SWV [SWVf]). All lesions underwent core needle biopsy or surgical excision. Differences among the SWV types in malignant and benign lesions were evaluated. We also assessed how different lesion types affected the SWV types. Receiver operating characteristic analysis was performed to assess the sensitivity and specificity of the SWV types in differentiating malignant from benign lesions.

RESULTS: Internal SWV was significantly higher than SWVb, SWVg, and SWVf; SWVb was significantly higher than SWVg and SWVf; and SWVg was significantly higher than SWVf in both malignant and benign groups (P < .05). All 4 SWV types were significantly higher in the malignant group than the benign group (P < .05). In the malignant group, grade 3 invasive ductal carcinoma had the highest SWVi. The sensitivity and specificity for differentiating malignant lesions were 55.2% and 95.8% for SWVi, 85.1% and 53.3% for SWVb, 68.2% and 69.6% for SWVg, and 67.2% and 66.0% for SWVf.

CONCLUSIONS: Acoustic radiation force impulse imaging has potential to characterize breast lesions, both internally and within the boundary zone, and to reflect changes in stiffness within surrounding glandular and subcutaneous fatty tissues caused by malignant tumors.}, } @article {pmid23341125, year = {2014}, author = {Uematsu, T and Kasami, M and Watanabe, J}, title = {Is evaluation of the presence of prepectoral edema on T2-weighted with fat-suppression 3 T breast MRI a simple and readily available noninvasive technique for estimation of prognosis in patients with breast cancer?.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {6}, pages = {684-692}, doi = {10.1007/s12282-013-0440-z}, pmid = {23341125}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/drug therapy/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/drug therapy/pathology ; Drug Resistance, Neoplasm/drug effects ; Edema/epidemiology/*pathology ; Female ; Humans ; Inflammatory Breast Neoplasms/drug therapy/pathology ; Lymph Nodes/diagnostic imaging/pathology ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {BACKGROUND: The specificity of breast MRI is only moderate. The unsatisfactory specificity of breast MRI has prompted evaluation of high signal intensity (SI) on T2-weighted imaging (T2WI). The purpose of the study was to investigate the prevalence of prepectoral edema determined using high SI on T2WI with fat-suppression 3 T MRI and to correlate its presence with prognostic factors of breast cancer.

METHODS: The retrospective study comprised 589 consecutive histopathologically confirmed lesions, 460 malignant and 129 benign, identified by 3 T MRI. Presence of prepectoral edema was evaluated on T2WI with fat suppression, and its diagnostic value for malignancies and correlation with clinicopathological findings in histopathologically confirmed breast cancer were assessed.

RESULTS: Prepectoral edema was present in 54 of the 460 breast cancers (9 % of the total 589) and none of the 129 benign lesions. Its sensitivity and specificity were 12 and 100 %, respectively. The positive predictive value was 100 %. Young age (p = 0.01), large tumor size (p < 0.0001), high histological grade (p < 0.0001), invasive ductal carcinoma (p < 0.0001), high lymphovascular invasion degree (p < 0.0001), high axillary lymph node positivity (p < 0.0001), high inflammatory breast cancer rate (p < 0.0001), high neoadjuvant chemotherapy rate (p < 0.0001), and chemoresistant breast cancers (p < 0.0001) were significantly associated with prepectoral edema. There was no association of the morphological lesion type on MRI and dynamic enhancement imaging pattern with the presence of prepectoral edema.

CONCLUSION: Prepectoral edema has low prevalence but is specific for breast cancer and correlated with prognostic factors.}, } @article {pmid23340254, year = {2013}, author = {Holloway, KR and Barbieri, A and Malyarchuk, S and Saxena, M and Nedeljkovic-Kurepa, A and Cameron Mehl, M and Wang, A and Gu, X and Pruitt, K}, title = {SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression.}, journal = {Molecular endocrinology (Baltimore, Md.)}, volume = {27}, number = {3}, pages = {480-490}, pmid = {23340254}, issn = {1944-9917}, support = {R01 CA155223/CA/NCI NIH HHS/United States ; CA155223/CA/NCI NIH HHS/United States ; }, mesh = {Aromatase/*genetics/metabolism ; Breast Neoplasms/*enzymology/*genetics ; Carcinoma, Ductal, Breast/enzymology/genetics/pathology ; Cell Line, Tumor ; Female ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Promoter Regions, Genetic ; Sirtuin 1/antagonists & inhibitors/*metabolism ; Sirtuin 2/antagonists & inhibitors/metabolism ; }, abstract = {Breast cancer remains one of the leading causes of death in women diagnosed with cancer. In breast cancer, aberrant expression of the CYP19A1 gene, which encodes the aromatase enzyme, contributes to increased intratumoral levels of estradiol. Regardless of whether this estrogen is produced by peripheral tissues or within specific subpopulations of cells within the breast tumor, it is clear that the aromatase enzymatic activity is critical for the growth of estrogen-dependent tumors. Currently, aromatase inhibitors have proven to be highly effective in blocking the growth of estrogen-dependent forms of breast cancer. CYP19A1 transcription is tightly controlled by 10 tissue-specific promoters. In breast cancer, however, aromatase transcription is driven by multiple promoters that somehow override the tissue-specific regulation of normal tissue. Here, we explore the role that the deacetylase, sirtuin-1 (SIRT1), plays in positively regulating aromatase in breast cancer. We demonstrate that the use of cambinol and the SIRT1/2 inhibitor VII, 2 small molecule inhibitors of SIRT1 and SIRT2, as well as small molecule inhibitors and small interfering RNA specific to SIRT1, all reduce the levels of aromatase mRNA. We further demonstrate that pharmacologic inhibition causes a marked reduction in aromatase protein levels. Additionally, by chromatin immunoprecipitation, we demonstrate that SIRT1 occupies the promoter regions PI.3/PII and PI.4, and its inhibition leads to increased acetylation of estrogen-related receptorα, a transcription factor that positively regulates CYP19A1 transcription in epithelial cells. Finally, we demonstrate by immunohistochemistry that SIRT1 is significantly up-regulated in invasive ductal carcinoma relative to normal tissue adjacent to tumor, further suggesting a role of SIRT1 in breast cancer. This work uncovers a new mechanism for the regulation of aromatase and provides rationale for further investigation of how the inhibition of specific sirtuins may provide a unique strategy for inhibiting aromatase that may complement or synergize with existing therapies.}, } @article {pmid23338716, year = {2013}, author = {Ehsan, N and Murad, S and Ashiq, T and Mansoor, MU and Gul, S and Khalid, S and Younas, M}, title = {Significant correlation of TLR4 expression with the clinicopathological features of invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {34}, number = {2}, pages = {1053-1059}, pmid = {23338716}, issn = {1423-0380}, mesh = {Adult ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Neoplasm Grading ; Prognosis ; Toll-Like Receptor 4/*metabolism ; }, abstract = {Toll-like receptor 4 belongs to the family of pattern recognition receptors and is therefore an important part of innate immunity. Since the last decade, Toll-like receptors (TLRs) have gained much interest in cancer research due to their role in tumor progression. However, there is scarcity of data evaluating TLR4 expression in different cell populations of tumor in relation to clinicopathological parameters of invasive ductal carcinoma of the breast. Therefore, we investigated TLR4 expression in 50 primary invasive ductal carcinoma and 17 lymph node sections through immunohistochemistry. Significant association of TLR4 expression with local metastasis and absence of necrosis was observed. The incidence of lymph node metastasis was higher in patients with high TLR4 expression in the tumor cells. We also observed an interesting inverse relationship of TLR4 with necrosis. In endothelial and lymphocytic population constituting breast tumors, a significant association of TLR4 expression was seen with the tumor grade. Therefore, we conclude that TLR4 expression is of biological interest both as a prognostic marker as well as a possible therapeutic target.}, } @article {pmid23337025, year = {2013}, author = {Foschini, MP and Morandi, L and Leonardi, E and Flamminio, F and Ishikawa, Y and Masetti, R and Eusebi, V}, title = {Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast.}, journal = {Human pathology}, volume = {44}, number = {7}, pages = {1310-1319}, doi = {10.1016/j.humpath.2012.09.022}, pmid = {23337025}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; Clone Cells ; Disease Progression ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/genetics ; Humans ; Middle Aged ; Precancerous Conditions/genetics/pathology ; }, abstract = {Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs.}, } @article {pmid23330703, year = {2014}, author = {Morrone, A and Bordignon, V and Barnabas, GA and Dassoni, F and Latini, O and Padovese, V and Ensoli, F and Cristaudo, A}, title = {Clinical-epidemiological features of contact dermatitis in rural and urban communities in northern Ethiopia: correlation with environmental or occupational exposure.}, journal = {International journal of dermatology}, volume = {53}, number = {8}, pages = {975-980}, doi = {10.1111/j.1365-4632.2012.05777.x}, pmid = {23330703}, issn = {1365-4632}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cobalt/toxicity ; Dermatitis, Allergic Contact/*epidemiology/etiology ; Eczema/chemically induced/epidemiology ; Ethiopia/epidemiology ; Female ; Foot Dermatoses/chemically induced/epidemiology ; Hand Dermatoses/chemically induced/epidemiology ; Head ; Humans ; Male ; Middle Aged ; Neck ; Nickel/toxicity ; Occupational Exposure/*adverse effects ; Patch Tests ; Perfume/toxicity ; Phenylenediamines/toxicity ; Potassium Dichromate/toxicity ; Prevalence ; Resins, Synthetic/toxicity ; Rural Population/*statistics & numerical data ; Torso ; Urban Population/*statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND: The widespread diffusion of low-quality products as well as the local cultural habits could be a relevant cause of allergic diseases in developing countries. In the present observational study, we explored the prevalence of allergic contact dermatitis in both rural and urban settings in northern Ethiopia, where skin diseases represent a frequent cause of morbidity. Clinical features and specific reactivities in association with environmental or occupational exposure were investigated.

PATIENTS AND METHODS: We patch tested 480 consecutive patients, visited at the Mekele IDC, exhibiting symptoms of contact dermatitis. A detailed medical history of each patient was collected.

RESULTS: A positive patch-test response was observed in 50% of subjects; nickel was the most frequent sensitizer (26.2%), followed by p-tert-butylphenol formaldehyde resin (10%), fragrance mix (7.1%), potassium dichromate (5.4%), cobalt chloride (4.6%), disperse blue (2.3%), and p-phenylenediamine (1.7%). Gender-related differences were analyzed for single allergen. Eczema represented the most common manifestation, affecting the head and neck as primary skin areas. While reactivity to nickel interested almost all the occupational categories, sensitization to other allergens could be ascribed to working habits or environmental exposure.

CONCLUSIONS: The results gathered from this study, the first one conducted within the Tigray region in Ethiopia, confirm the need to take appropriate measures to limit the nickel rate in metal objects and may be useful to design allergenic series suitable for patch testing in those geographical settings.}, } @article {pmid23330677, year = {2013}, author = {Jablonska, K and Pula, B and Zemla, A and Owczarek, T and Wojnar, A and Rys, J and Ambicka, A and Podhorska-Okolow, M and Ugorski, M and Dziegiel, P}, title = {Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.}, journal = {Journal of pineal research}, volume = {54}, number = {3}, pages = {334-345}, doi = {10.1111/jpi.12032}, pmid = {23330677}, issn = {1600-079X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/chemistry ; Breast Neoplasms/chemistry/genetics/*metabolism ; Carcinoma, Ductal, Breast/chemistry/genetics/*metabolism ; Female ; Fibrocystic Breast Disease/chemistry/genetics/metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Real-Time Polymerase Chain Reaction ; Receptor, Melatonin, MT1/*biosynthesis/genetics ; Statistics, Nonparametric ; }, abstract = {In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC.}, } @article {pmid23320919, year = {2013}, author = {Datta, G and Maisnam, D}, title = {Lymphoma and metastatic breast cancer presenting with palpable axillary and inguinal lymphadenopathy in a 40-year-old man with rheumatoid arthritis on anti-tumor necrosis factor α therapy: a case report.}, journal = {Journal of medical case reports}, volume = {7}, number = {}, pages = {23}, pmid = {23320919}, issn = {1752-1947}, abstract = {INTRODUCTION: We present the case of a 40-year-old man with severe rheumatoid arthritis being treated with high-dose anti-tumor necrosis factor α therapy (adalimumab), who developed simultaneous lymphoma and breast cancer with lymph node metastases. We describe strategies for investigations and management of this presentation.

CASE PRESENTATION: A 40-year-old Caucasian man with severe rheumatoid arthritis being treated with high-dose adalimumab presented to our facility with a swollen leg and palpable left groin and left axillary lumps and a left nipple lesion. Left lower limb ultrasound, computed tomography and positron emission tomography scans showed extensive lymphadenopathy. Core biopsies of the left groin, axilla and nipple lesion showed this to be concurrent diffuse B-cell lymphoma and locally metastatic invasive ductal carcinoma of the breast. He underwent a left mastectomy with axillary clearance, and adjuvant fluorouracil, epirubicin and cyclophosphamide chemotherapy with rituximab, and the adalimumab was stopped.

CONCLUSIONS: The findings from our patient's case should increase awareness that patients with severe rheumatoid arthritis, especially if they are on high-dose biological treatments, have the potential to develop lymphoma, which in turn increases the risk of developing other primary tumors, so that in rare cases a patient may have concurrent tumors. Assessment and management of these patients is challenging and should include computed tomography scans of the of neck, thorax, abdomen and pelvis, including a fludeoxyglucose positron emission tomography/computed tomography scan, bone marrow testing and appropriate core biopsies and discussion at multidisciplinary team meetings about treatment of the separate tumors in the presence of hematologists, oncologists, surgeons and rheumatologists.}, } @article {pmid23314091, year = {2012}, author = {Nakash, O and Saguy, T and Levav, I}, title = {The effect of social identities of service-users and clinicians on mental health disparities: A review of theory and facts.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {49}, number = {3}, pages = {202-210}, pmid = {23314091}, issn = {2617-2402}, mesh = {*Health Status Disparities ; Humans ; Mental Health/*ethnology ; *Professional-Patient Relations ; *Social Identification ; }, abstract = {Mental health disparities are differences in health status, risks and care favoring members of advantaged over disadvantaged social groups. the contrasting social identities of clinicians and service-users may account for potential disparities found in clinical encounters, reflected, for example, in the provision of substandard care. the imputed mechanisms, however, remain unknown. Drawing on social psychological research we delineate a model to assist in identifying those mechanisms. we review the literature on processes rooted in social categorization (outgroup bias) and in social power (impaired perspective taking, making automatic attributions) and suggest that the contrasting social identities of clinicians and service-users can partially account for why discordant, compared to concordant ethnic identities in clinical encounters may produce worse outcomes, measured by the quality of the working alliance and the accuracy of diagnostic decisions. we provide preliminary evidence for the proposed model and submit a research agenda to inform evidence-based interventions to counter the negative outcomes of discordant encounters.}, } @article {pmid23304480, year = {2012}, author = {Seretis, C and Seretis, F and Lagoudianakis, E and Politou, M and Gemenetzis, G and Salemis, NS}, title = {Enhancing the accuracy of platelet to lymphocyte ratio after adjustment for large platelet count: a pilot study in breast cancer patients.}, journal = {International journal of surgical oncology}, volume = {2012}, number = {}, pages = {653608}, pmid = {23304480}, issn = {2090-1410}, abstract = {Background. The objective of our study is to investigate the potential effect of adjusting preoperative platelet to lymphocyte ratio, an emerging biomarker of survival in cancer patients, for the fraction of large platelets. Methods. A total of 79 patients with breast neoplasias, 44 with fibroadenomas, and 35 with invasive ductal carcinoma were included in the study. Both conventional platelet to lymphocyte ratio (PLR) and the adjusted marker, large platelet to lymphocyte ratio (LPLR), were correlated with laboratory and histopathological parameters of the study sample. Results. LPLR elevation was significantly correlated with the presence of malignancy, advanced tumor stage, metastatic spread in the axillary nodes and HER2/neu overexpression, while PLR was only correlated with the number of infiltrated lymph nodes. Conclusions. This is the first study evaluating the effect of adjustment for large platelet count on improving PLR accuracy, when correlated with the basic independent markers of survival in a sample of breast cancer patients. Further studies are needed in order to assess the possibility of applying our adjustment as standard in terms of predicting survival rates in cancer.}, } @article {pmid23304239, year = {2012}, author = {Faheem, M and Mahmood, H and Khurram, M and Qasim, U and Irfan, J}, title = {Estrogen receptor, progesterone receptor, and Her 2 Neu positivity and its association with tumour characteristics and menopausal status in a breast cancer cohort from northern Pakistan.}, journal = {Ecancermedicalscience}, volume = {6}, number = {}, pages = {283}, pmid = {23304239}, issn = {1754-6605}, abstract = {OBJECTIVES: To measure the frequency of estrogen receptor (ER), progesterone receptor (PR), and Her 2 Neu positivity and to study their association with tumour characteristics and menopausal status in a breast cancer cohort from Northern Pakistan.

METHODOLOGY: Patients attending NORI with histopathologically proven diagnosis of invasive ductal carcinoma of the breast were included after providing informed consent. Age, menopausal status, and tumour size were recorded. The presence or absence of nodal involvement (including site and number), distant metastases, sites of metastases, skin involvement, chest wall involvement, recurrent disease, and bilateral breast cancer were noted along with ER, PR, and Her 2 Neu status. Mean ± standard deviations were calculated for continuous variables like age. Frequency and percentage were calculated for categorical variables like ER, PR, and Her 2 Neu status. Association of ER, PR, and Her 2 Neu status with menopausal status and tumour-related characteristics were sought employing t test, x(2)square test, and ANOVA wherever appropriate. P value >0.05 was considered significant.

RESULTS: There were 1226 patients included in the study. Mean patient age was 48.04 ± 11.97 years, and 743 (60.6%) patients were premenopausal. ER, PR, and Her 2 Neu were found positive in 763 (62.2%), 738 (60.1%), and 478 (38.9%) patients, respectively. Significant association (P < 0.05) was found between ER, PR positivity, and Her 2 Neu over expression with menopausal status, tumour size, involvement of skin, chest wall and lymph nodes and the presence of distant metastases. However, no significant association was detected between ER, PR, Her 2 Neu and recurrent disease.

CONCLUSIONS: The frequency of expression of hormonal receptors in breast cancer patients from Northern Pakistan is the same as reported in the literature although overexpression of Her 2 Neu is a little higher in our population. There is an inverse relationship between hormonal receptors expression and Her 2 Neu expression. Postmenopausal women have a higher incidence of ER and PR positivity and Her 2 Neu negativity. ER and PR negativity and Her 2 Neu positivity are associated with more advanced disease and poor outcome.}, } @article {pmid23302996, year = {2012}, author = {Shapochka, DO and Zaletok, SP and Gnidyuk, MI}, title = {Relationship between NF-κB, ER, PR, Her2/neu, Ki67, p53 expression in human breast cancer.}, journal = {Experimental oncology}, volume = {34}, number = {4}, pages = {358-363}, pmid = {23302996}, issn = {2312-8852}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/biosynthesis ; NF-kappa B/analysis/biosynthesis ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/analysis/biosynthesis ; Receptors, Estrogen/analysis/biosynthesis ; Receptors, Progesterone/analysis/biosynthesis ; Tumor Suppressor Protein p53/analysis/biosynthesis ; }, abstract = {AIM: The aim of the present study was to investigate expression patterns of transcription factor NF-κB (p50 and p65), ER, PR, Her2/neu, Ki-67 and p53 in tumor tissue of patients with breast cancer (BC) and analyze correlation between these markers.

PATIENTS AND METHODS: 62 BC patients previously not treated with chemo- or radiotherapy were included in the study. All tumors belong to invasive ductal carcinoma of different grade. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections.

RESULTS: The correlation between tumor grade and expression of ER, PR, Ki-67 and p53 was defined. NF-κB expression was found to be changed dependent on expression of ER, PR and p53 and also on molecular subtype (luminal, Her2-positive, hybrid, basal-like). The highest levels of NF-κB, Ki-67 and p53 were found in Her2/neu+ and basal-like tumor subtypes.

CONCLUSION: The increase of nuclear expression of NF-κB correlates with a decrease of expression of steroid hormone receptors (ER and PR), increase of p53 accumulation, and is associated with Her2-positive and basal-like tumor types.}, } @article {pmid23301641, year = {2013}, author = {Korwar, AM and Bhonsle, HS and Ghole, VS and Gawai, KR and Koppikar, CB and Kulkarni, MJ}, title = {Proteomic profiling and interactome analysis of ER-positive/HER2/neu negative invasive ductal carcinoma of the breast: towards proteomics biomarkers.}, journal = {Omics : a journal of integrative biology}, volume = {17}, number = {1}, pages = {27-40}, doi = {10.1089/omi.2012.0054}, pmid = {23301641}, issn = {1557-8100}, mesh = {Amino Acid Sequence ; Biomarkers, Tumor/*metabolism ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal/*metabolism/pathology ; Female ; Genes, erbB-2 ; Humans ; Molecular Sequence Data ; Neoplasm Invasiveness ; *Proteomics ; Receptors, Estrogen/*metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Breast cancer, especially ER positive/HER2/neu negative IDC, is the predominant subtype of invasive ductal carcinoma. Although proteomic approaches have been used towards biomarker discovery in clinical breast cancer, ER positive/HER2/neu negative IDC is the least studied subtype. To discover biomarkers, as well as to understand the molecular events associated with disease progression of estrogen receptor positive/HER2/neu negative subtype of invasive ductal carcinoma, differential protein expression profiling was performed by using LC-MS(E) (MS at elevated energy). A total of 118 proteins were identified, of which 26 were differentially expressed. These identified proteins were functionally classified and their interactions and coexpression were analyzed by using bioinformatic tools PANTHER (Protein Analysis THrough Evolutionary Relationships) and STRING (Search Tool for the Retrieval of Interacting Genes). These proteins were found to be upregulated and were involved in cytoskeletal organization, calcium binding, and stress response. Interactions of annexin A5, actin, S100 A10, glyceraldehyde 3 phosphate dehydrogenase, superoxide dismutase 1, apolipoprotein, fibrinogen, and heat shock proteins were prominent. Differential expression of these proteins was validated by two-dimensional gel electrophoresis and Western blot analysis. The cluster of these proteins may serve as a signature profile for estrogen receptor positive/ HER2/neu negative subtype.}, } @article {pmid23301423, year = {2012}, author = {López-Narváez, RA and Garza-Montemayor, ML and Garza-García, NL and Ojeda-Mendez, EE and Rangel-Nava, H and Méndez-Lozano, D and Morales-Caballero, FG}, title = {[Detection of invasive breast lobular carcinoma by image analysis: comparison between mammography and ultrasound].}, journal = {Ginecologia y obstetricia de Mexico}, volume = {80}, number = {5}, pages = {320-326}, pmid = {23301423}, issn = {0300-9041}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Female ; Humans ; *Mammography ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; *Ultrasonography, Mammary ; Young Adult ; }, abstract = {BACKGROUND: Early detection of lobular cancer has for long implied a challenge for diagnostic imaging due to the peculiar histology it presents that makes clinical and radiology detection rather difficult.

OBJECTIVE: The aim of our study was to compare the sensitivity and specificity of mammography and ultrasound for the diagnosis of invasive breast lobular carcinoma.

MATERIAL AND METHODS: This is a retrospective study of women with histopathological diagnosis of invasive breast lobular carcinoma in the period between September 2006 and August 2009. All patients underwent mammography and ultrasound. The final pathology report was used as reference standard and the sensitivity and specificity of mammography and ultrasound were evaluated statistically using chi-square test (chi2).

RESULTS: The analysis included 654 patients who underwent biopsy. Among them, 148 (22.62%) were positive and 506 (77.37%) negative for cancer. The average age was 48 years (range 18-89). The sensitivity of ultrasound was higher in the group of invasive lobular cancer (ILC) in 14/14 (100%) cases, in contrast to 87/111 (78%) cases of invasive ductal carcinoma (IDC) and 9/18 (50 %) cases of ductal carcinoma in situ (DCIS). The mammography showed greater sensitivity in the group of DCIS in 17/18 (94%) cases, unlike 9/14 (64%) cases of ILC and 89/111 (80%) cases of IDC.

CONCLUSIONS: Ultrasound improves the detection of ILC with sensitivity up to 100% compared to 64% by mammography. The combination of both diagnostic tests showed sensitivity equal to the ultrasound, but it decreased 30% the specificity in this group.}, } @article {pmid23299541, year = {2013}, author = {Delpech, Y and Coutant, C and Hsu, L and Barranger, E and Iwamoto, T and Barcenas, CH and Hortobagyi, GN and Rouzier, R and Esteva, FJ and Pusztai, L}, title = {Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.}, journal = {British journal of cancer}, volume = {108}, number = {2}, pages = {285-291}, pmid = {23299541}, issn = {1532-1827}, support = {T32 CA009666/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*drug therapy/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology/surgery ; Carcinoma, Lobular/*drug therapy/mortality/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoadjuvant Therapy ; Receptors, Estrogen/metabolism ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to compare clinical and pathological outcomes after neoadjuvant chemotherapy between oestrogen receptor (ER)-positive invasive pure lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).

METHODS: This analysis included 1895 patients (n=177 ILC; n=1718 IDC), with stage I-III breast cancer, who received neoadjuvant chemotherapy. Clinical and pathological response rates, the frequency of positive surgical margins and rate of breast-conserving surgery were compared.

RESULTS: There was a trend for fewer good clinical responses in ILC compared with IDC. Tumour downstaging was significantly less frequent in ILC. Positive or close surgical resection margins were more frequent in ILC, and breast-conserving surgery was less common (P<0.001). These outcome differences remained significant in multivariate analysis, including tumour size, nodal status, age, grade and type of chemotherapy. Invasive pure lobular carcinoma was also associated with a significantly lower pathological complete response (pCR) rate in univariate analysis, but this was no longer significant after adjusting for tumour size and grade.

CONCLUSION: Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC. Pathological complete responses are rare in both groups, but do not significantly differ after adjusting for other variables.}, } @article {pmid23297753, year = {2013}, author = {Hasebe, T}, title = {Tumor-stromal interactions in breast tumor progression--significance of histological heterogeneity of tumor-stromal fibroblasts.}, journal = {Expert opinion on therapeutic targets}, volume = {17}, number = {4}, pages = {449-460}, doi = {10.1517/14728222.2013.757305}, pmid = {23297753}, issn = {1744-7631}, mesh = {Animals ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; *Cell Communication ; Disease Progression ; Female ; Fibroblasts/metabolism/pathology ; Fibrosis ; Humans ; Mammary Glands, Animal/metabolism/pathology ; Mammary Glands, Human/*metabolism/pathology ; Stromal Cells/*metabolism/pathology ; }, abstract = {INTRODUCTION: Existing pathological diagnostic protocols for breast cancer do not fully reflect the biological characteristics of tumor stromata. To improve the pathological diagnosis of breast cancer, a new pathological diagnostic method capable of assessing the degree of breast cancer malignancy based on the histological features of the tumor stroma is needed.

AREAS COVERED: The presence of a fibrotic focus (FF), which consists of fibroblasts or collagen fibers, and the presence of atypical tumor-stromal fibroblasts are significantly associated with nodal metastasis or distant-organ metastasis in patients with invasive ductal carcinoma (IDC) of the breast. FF is the only factor that is significantly associated with an increase in tumor angiogenesis. The importance of FF and atypical tumor-stromal fibroblasts clearly indicates that the malignant potential of IDC does not depend only on the biological characteristics of the tumor cell, but also on those of the tumor stroma.

EXPERT OPINION: The biological characteristics of fibroblasts forming an FF or atypical tumor-stromal fibroblasts probably differ from those of fibroblasts located outside an FF or ordinary tumor-stromal fibroblasts. Thus, similar to tumor cells, the heterogeneity of tumor-stromal fibroblasts probably influences the outcome of patients with IDC of the breast.}, } @article {pmid23292359, year = {2013}, author = {Kim, Y and Othmer, HG}, title = {A hybrid model of tumor-stromal interactions in breast cancer.}, journal = {Bulletin of mathematical biology}, volume = {75}, number = {8}, pages = {1304-1350}, pmid = {23292359}, issn = {1522-9602}, support = {R01 GM029123/GM/NIGMS NIH HHS/United States ; GM-29123/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Neoplasms/*etiology/pathology/physiopathology ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Epidermal Growth Factor/physiology ; Female ; Humans ; Mathematical Concepts ; *Models, Biological ; Neoplasm Invasiveness ; Signal Transduction ; Stromal Cells/pathology/physiology ; Transforming Growth Factor beta/physiology ; Tumor Microenvironment ; }, abstract = {Ductal carcinoma in situ (DCIS) is an early stage noninvasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix (ECM) surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. Here we develop a mathematical model that incorporates the cross-talk between stromal and tumor cells, which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-β signaling pathways and show how up- or down-regulation of components in these pathways affects cell growth and proliferation. We then study a hybrid model for the interaction of cells with the tumor microenvironment (TME), in which epithelial cells (ECs) are modeled individually while the ECM is treated as a continuum, and show how these interactions affect the early development of tumors. Finally, we incorporate breakdown of the epithelium into the model and predict the early stages of tumor invasion into the stroma. Our results shed light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.}, } @article {pmid23286959, year = {2013}, author = {Sakr, RA}, title = {[Does molecular biology play any role in ductal carcinoma in situ?].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {41}, number = {1}, pages = {45-53}, doi = {10.1016/j.gyobfe.2012.11.004}, pmid = {23286959}, issn = {1769-6682}, mesh = {Apoptosis/genetics ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology/therapy ; Cell Cycle Proteins/analysis/genetics ; Female ; Humans ; Ki-67 Antigen/analysis/genetics ; Mastectomy ; Neoplasm Invasiveness/*genetics/pathology ; Prognosis ; Receptor, ErbB-2/analysis/genetics ; Receptors, Steroid/analysis/genetics ; Risk Factors ; }, abstract = {The natural history of ductal carcinoma in situ (DCIS) is not fully elucidated, but it is recognized that DCIS is the true precursor of invasive carcinoma. Studies could show that DCIS is as heterogeneous as invasive ductal carcinoma, yet, they were unable to predict which DCIS will progress to invasion. Several biomarkers were also demonstrated to have a certain prognostic value. However, except for estrogen receptors and HER2, biomarkers are not yet widely used in clinical practice since their predictive value has not proven to be better than the grade and the classical classifying systems of DCIS. Identifying biomarkers for risk of invasiveness in DCIS could be of great value to help high risk patients through the management of their disease and to avoid overtreatment in low risk patients.}, } @article {pmid23282797, year = {2013}, author = {Nakash, O and Alegría, M}, title = {Examination of the role of implicit clinical judgments during the mental health intake.}, journal = {Qualitative health research}, volume = {23}, number = {5}, pages = {645-654}, pmid = {23282797}, issn = {1049-7323}, support = {P50 MH073469/MH/NIMH NIH HHS/United States ; P60 MD002261/MD/NIMHD NIH HHS/United States ; P60 MD0 02261/MD/NIMHD NIH HHS/United States ; 1P50 MH0 73469/MH/NIMH NIH HHS/United States ; }, mesh = {Female ; Humans ; Interview, Psychological ; Interviews as Topic ; Judgment ; Male ; Mental Disorders/*diagnosis/psychology ; Practice Patterns, Physicians' ; Psychiatry ; Psychology, Clinical ; }, abstract = {We examined the characteristics of therapists' implicit clinical judgments during the mental health intake. Following the intake sessions with new clients, we conducted 129 semistructured interviews with 47 therapists. We found that 82% of therapists and 75% of interviews included reference to implicit clinical judgments. Therapists referred to these judgments as a cognitive process that relied on knowledge acquired through past clinical experiences and was primarily based on nonverbal cues and affective communication. Therapists used implicit processes when evaluating how to facilitate a good working alliance, what diagnostic information to collect, and how to decide on a diagnosis. The majority of therapists described elements of good rapport, such as being listened to, as central for a positive outcome of the intake. We concluded that implicit clinical judgments were vital to allow therapists to integrate the plethora of information from different channels of communication they collect during the intake.}, } @article {pmid23276718, year = {2013}, author = {Kim, YH and Kim, JH and Choi, YW and Lim, SK and Yim, H and Kang, SY and Chung, YS and Lee, GY and Park, TJ}, title = {Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.}, journal = {Experimental and molecular pathology}, volume = {94}, number = {2}, pages = {360-365}, doi = {10.1016/j.yexmp.2012.12.002}, pmid = {23276718}, issn = {1096-0945}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Proteasome Endopeptidase Complex/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Up-Regulation ; Young Adult ; }, abstract = {Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p=0.014) and ErbB2 positivity (p=0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.}, } @article {pmid23274650, year = {2013}, author = {Yu, FD and Yang, SY and Li, YY and Hu, W}, title = {Co-expression network with protein-protein interaction and transcription regulation in malaria parasite Plasmodium falciparum.}, journal = {Gene}, volume = {518}, number = {1}, pages = {7-16}, doi = {10.1016/j.gene.2012.11.092}, pmid = {23274650}, issn = {1879-0038}, mesh = {Algorithms ; *Gene Expression Regulation ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*genetics/growth & development/metabolism/*pathogenicity ; Protozoan Proteins/genetics/*metabolism ; }, abstract = {BACKGROUND: Malaria continues to be one of the most severe global infectious diseases, as a major threat to human health and economic development. Network-based biological analysis is a promising approach to uncover key genes and biological processes from a network viewpoint, which could not be recognized from individual gene-based signatures.

RESULTS: We integrated gene co-expression profile with protein-protein interaction and transcriptional regulation information to construct a comprehensive gene co-expression network of Plasmodium falciparum. Based on this network, we identified 10 core modules by using ICE (Iterative Clique Enumeration) algorithm, which were essential for malaria parasite development in intraerythrocytic developmental cycle (IDC) stages. In each module, all genes were highly correlated probably due to co-regulation or formation of a protein complex. Some of these genes were recognized to be differentially coexpressed among three close-by IDC stages. The gene of prpf8 (PFD0265w) encoding pre-mRNA processing splicing factor 8 product was identified as DCGs (differentially co-expressed genes) among IDC stages, although this gene function was seldom reported in previous researches. Integrating the species-specific gene prediction and differential co-expression gene detection, we found some modules could perform species-specific functions according to some of genes in these modules were species-specific genes, like the module 10. Furthermore, in order to reveal the underlying mechanisms of the erythrocyte invasion by P. falciparum, Steiner Tree algorithm was employed to identify the invasion subnetwork from our gene co-expression network. The subnetwork-based analysis indicated that some important Plasmodium parasite specific genes could corporate with each other and be co-regulated during the parasite invasion process, which including a head-to-head gene pair of PfRH2a (PF13_0198) and PfRH2b (MAL13P1.176).

CONCLUSIONS: This study based on gene co-expression network could shed new insights on the mechanisms of pathogenesis, even virulence and P. falciparum development.}, } @article {pmid23268006, year = {2012}, author = {Yokoyama, S and Sasaki, Y and Hashimoto, K and Takeda, M and Toshiyama, R and Fukuda, S and Naito, A and Matsumoto, S and Tokuoka, M and Ide, Y and Matsuyama, J and Morimoto, T and Fukushima, Y and Nomura, T and Kodama, K and Shiba, I and Takeda, M}, title = {[A case of invasive ductal carcinoma of the pancreas originating from an intraductal papillary mucinous tumor that was initially misdiagnosed as a mucinous cystic tumor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2149-2151}, pmid = {23268006}, issn = {0385-0684}, mesh = {Adenocarcinoma, Mucinous/*diagnosis ; Carcinoma, Pancreatic Ductal/*diagnosis ; Carcinoma, Papillary/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*diagnosis ; }, abstract = {A 57-year-old woman was discovered to have a cystic tumor, 8 cm in diameter, at the pancreas tail, during routine screening with ultrasonography. The patient did not complain of tenderness, and no abdominal mass was palpable at physical examination. Enhanced computed tomography(CT) revealed that the tumor had mural nodules in the cyst wall, and we suspected it to be a malignant tumor that had occurred in the mucinous cystic neoplasm(MCN). Therefore, surgical resection was attempted, upon which the tumor was found to be hard and the surrounding tissue adhered widely to the stomach. We separated it carefully from the stomach and then performed a distal pancreatectomy. The cut surface revealed that the posterior wall of the cystic tumor was partly thickened, and microscopic examination revealed it to be invasive ductal carcinoma. No ovarian-like stroma was involved and some degree of dysplasia(PanIN 1-3) was found in the neighboring tissues. Therefore, we re-diagnosed it to be invasive ductal carcinoma of the pancreas derived from intraductal papillary mucinous tumor(IPMT), not from MCN. The patient received adjuvant chemotherapy, although 5 months later multiple lung metastases had appeared. The international consensus guidelines for management of IPMN and MCN of the pancreas suggest that they can usually be distinguished preoperatively, if there is a complete understanding of their clinical and imaging features. However, we sometimes find it difficult to distinguish the 2, because some IPMN or MCN cases have shared preoperative features. Herein, we report the case of invasive ductal carcinoma of the pancreas derived from IPMT that was originally misdiagnosed as a MCN.}, } @article {pmid23267983, year = {2012}, author = {Hara, Y and Sakurai, K and Enomoto, K and Matsumoto, K and Ueda, Y and Hagiwara, M and Waga, E and Nagashima, S and Tani, M and Amano, S}, title = {[Complete response of advanced breast cancer with lymph node metastases to nab-paclitaxel therapy-report of a case].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2080-2082}, pmid = {23267983}, issn = {0385-0684}, mesh = {Albumins/*therapeutic use ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Paclitaxel/*therapeutic use ; }, abstract = {We report a case of breast cancer with lymph node metastases. A complete response was recognized in response to nab-paclitaxel as a first-line therapy after recurrence. The patient was a 50-year-old woman who had a tumor in her right breast. We palpated a mass with clear boundaries in her right breast. The tumor was 2 cm in diameter. Core-needle biopsy of the breast tumor led to a diagnosis of invasive ductal carcinoma (estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative). She received 4 cycles of EC (E: 90 mg/m2/tri-weekly; C: 600 mg/m2 /tri-weekly) plus 4 cycles of TC(T: 75 mg/m2/tri-weekly; C: 600 mg/m2/tri-weekly)as preoperative adjuvant chemotherapy. After chemotherapy, she underwent quadrantectomy plus axillary lymph node dissection. Six months after the operation, lymph node metastases were observed in her right supraclavicular lymph nodes. She received 8 cycles of nab-paclitaxel(260 mg/m2/tri-weekly) therapy. After 8 cycles of treatment, ultrasonography and computed tomography revealed the disappearance of the metastatic lymph nodes. Therefore, a clinical complete response was observed.}, } @article {pmid23267982, year = {2012}, author = {Yamauchi, S and Nakagawa, T and Kasahara, M and Sugimoto, H and Ishiba, T and Tamura, N and Nagahara, M and Sato, T and Sugihara, K}, title = {[A case of metastatic breast cancer with bilateral hydronephrosis effectively treated with capecitabine].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2077-2079}, pmid = {23267982}, issn = {0385-0684}, mesh = {Adenocarcinoma, Scirrhous/*drug therapy/secondary ; Antimetabolites, Antineoplastic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Female ; Fluorouracil/*analogs & derivatives/therapeutic use ; Humans ; Hydronephrosis/*etiology ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/secondary ; }, abstract = {A 54-year-old female was diagnosed with invasive ductal carcinoma (pT3N1M0, Stage IIIA, estrogen receptor positive [ER (+)], progesterone receptor positive [PgR (+)], human epidermal growth factor receptor type 2 [HER2] score 0) and was treated by preoperative chemotherapy with weekly paclitaxel followed by 5-fluorouracil(5-FU) plus epirubicin plus cyclophosphamide regimen(FEC). Partial mastectomy with axillary dissection was performed. The pathological examination disclosed that the tumor was scirrhous carcinoma, and a pathological partial response was achieved by chemotherapy. Multiple bone metastases were detected 18 months after the surgery during treatment with letrozole as adjuvant therapy. Retroperitoneal metastases with hydronephrosis and a lung metastasis were detected 28 months after the surgery, even though exemestane and zoledronate were administrated after detection of the bone metastases. Chemotherapy with capecitabine was started and she recovered from hydronephrosis 4 months after the start of treatment. After 32 months from the first treatment with capecitabine, the patient is presently alive without hydronephrosis due to continued chemotherapy.}, } @article {pmid23267981, year = {2012}, author = {Yoshitomi, S and Tsuji, H}, title = {[A case of recurrent breast cancer with solitary adrenal metastasis treated with surgery and endocrine therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2074-2076}, pmid = {23267981}, issn = {0385-0684}, mesh = {Adrenal Gland Neoplasms/*drug therapy/secondary/surgery ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Female ; Humans ; Middle Aged ; Recurrence ; Toremifene/*therapeutic use ; }, abstract = {We present a case in which a 46-year-old woman underwent mastectomy (Bt+AX) for right breast cancer (T4bN0M0, Stage IIIB) at the age of 42. A histopathological examination confirmed her cancer to be an invasive ductal carcinoma n (-),ER (+), PgR (+),HER 2 (1+). For postoperative medication therapy, she was taking goserelin plus tamoxifen for 2 years and tamoxifen thereafter. A right adrenal tumor was discovered during a follow-up CT scan and MRI after the operation. There was no indication of metastasis in any other location. A laparoscopic right adrenalectomy was performed to establish a definitive diagnosis and to cure the cancer. According to the histopathological examination, the tumor was ER (+), PgR (+), and HER2 (0) and metastasized from the breast. After this operation, the regimen was changed to high- dose toremifene as endocrine therapy. No recurrence of the cancer has been reported 2 years and 4 months after the operation. In most cases, metastasis to the adrenal gland is due to systemic metastasis as seen in the last stage of breast cancer, and a solitary adrenal gland metastasis from breast cancer is extremely rare. The combination of surgical removal and medication for solitary distant metastasis from breast cancer may be effective in improving the long-term survival rate.}, } @article {pmid23267979, year = {2012}, author = {Ueda, H and Nakagawa, T and Sato, T and Nagahara, M and Sugihara, K}, title = {[A case of breast cancer liver metastases with jaundice responding to trastuzumab monotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2068-2070}, pmid = {23267979}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Female ; Humans ; Jaundice/*etiology ; Liver Neoplasms/complications/*drug therapy ; Middle Aged ; Neoplasm Staging ; Trastuzumab ; }, abstract = {We report the case of a 60-year-old female with liver dysfunction resulting from diffuse liver metastases, which, atypically, had originated from breast cancer. She responded remarkably well to trastuzumab monotherapy. She was referred to our hospital because of left breast cancer with multiple general lymphadenopathies. She presented with jaundice and liver dysfunction without a space-occupying lesion or a dilatation of the intrahepatic bile duct on computed tomography images. A liver biopsy was done to rule out autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis, and histopathological examination showed adenocarcinoma in the lymph duct of the liver. Both the primary breast cancer and the liver metastases were negative for hormone receptor expression(ER-, PR-), but overexpressed HER2(HercepTest 3+). She was diagnosed as invasive ductal carcinoma(T1N3cM1, Stage IV). We started trastuzumab monotherapy, which improved her jaundice and liver dysfunction, and resulted in a decrease in lymph node size.}, } @article {pmid23267972, year = {2012}, author = {Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Waga, E and Enomoto, K and Amano, S}, title = {[The problems of breast-conserving surgery for calcification undetected by ultrasonography].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2048-2050}, pmid = {23267972}, issn = {0385-0684}, mesh = {Breast Neoplasms/complications/diagnostic imaging/*pathology/surgery ; Calcinosis/etiology/*surgery ; Carcinoma, Ductal, Breast/complications/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Sentinel Lymph Node Biopsy ; Ultrasonography ; }, abstract = {The patient was a 58-year-old woman. Mammography showed grouped heterogeneous calcifications in the M area of the right breast. The area of the grouped heterogeneous calcifications was 1 cm in diameter. A vacuum-assisted biopsy (VAB) of the area led to a diagnosis of invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for human epidermal growth factor receptor type 2/neu protein expression. A micro mark was made by VAB enforcement in the lesion. At operation, we performed ultrasonography to detect the cancer lesion, but we could not detect the micro mark. It was difficult to determine the resection area. We detected architectural distortion after VAB and determined the resection area. Breast-conserving surgery and a sentinel lymph node biopsy was performed. Histopathologically, the surgical margins were negative and the sentinel lymph node was negative for cancer. This case suggested that it was necessary to make a new micro mark.}, } @article {pmid23267971, year = {2012}, author = {Hirano, T and Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Enomoto, K and Amano, S}, title = {[Lapatinib is useful for metastatic breast cancer patients who cannot be treated with trastuzumab-report of a case].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2045-2047}, pmid = {23267971}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Agents/*therapeutic use ; Biopsy, Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Female ; Humans ; Lapatinib ; Liver Neoplasms/*drug therapy/secondary ; Mastectomy ; Neoplasm Staging ; Quinazolines/*therapeutic use ; Trastuzumab ; }, abstract = {The patient was a 71-year-old woman. Mammography revealed an irregularly shaped mass in the U area of her left breast. Ultrasonography revealed an irregularly shaped mass in the C area of her breast. The mass was 22 mm in diameter. Core-needle biopsy of the area led to a diagnosis of invasive ductal carcinoma. The lesion was negative for estrogen receptor and progesterone receptor expression and positive for human epidermal growth factor receptor 2 protein expression. Distant metastasis was not detected. Muscle-preserving mastectomy and lymph node dissection were performed. Eight months after the operation, multiple liver metastases were found. We attempted to treat these metastases with trastuzumab. However, an infusion reaction was recognized. Therefore, we attempted treatment with lapatinib and capecitabine. This treatment was administered for 2 months without incident. After 2 months, hand-foot syndrome was recognized. Then, we attempted treatment with lapatinib alone. Lapatinib alone was effective against the multiple liver metastases. The patient's condition has remained stable for 1 year after treatment.}, } @article {pmid23267970, year = {2012}, author = {Aomatsu, N and Kashiwagi, S and Asano, Y and Morisaki, T and Nakamura, M and Kawajiri, H and Takashima, T and Onoda, N and Ishikawa, T and Hirakawa, K}, title = {[A successful case of a super-elderly breast cancer patient treated with hormone therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2042-2044}, pmid = {23267970}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/pathology ; Female ; Humans ; Neoplasm Staging ; Nitriles/*therapeutic use ; Quality of Life ; Triazoles/*therapeutic use ; Ultrasonography ; }, abstract = {A 104-year-old female patient with a left breast mass was admitted to our hospital. Ultrasonography showed an irregular and low-echoic mass of about 2.4×2.4×1.4 cm size in the left breast EAC area. Core needle biopsy examination indicated invasive ductal carcinoma of the breast: ER (+), PR (+), and HER2 (-). An overall examination did not show a distant metastasis. We diagnosed her with left breast cancer(luminal A type) T2N0M0, stage IIA. We administered anastrozole at a dose of 1 mg/day. After 6 months, the primary tumor diameter was reduced to 2.1 cm, and the effect of anastrozole was considered a clinical partial response. The patient did not experience any adverse events during treatment. The partial response was maintained for about 2 years. We experienced a successful case of a super-elderly breast cancer patient treated with anastrozole. We conclude that hormone therapy is a useful treatment for super-elderly postmenopausal women with estrogen receptor-positive breast cancer.}, } @article {pmid23267968, year = {2012}, author = {Waga, E and Sakurai, K and Fujisaki, S and Maeda, T and Nagashima, S and Hara, Y and Tomita, R and Suzuki, S and Enomoto, K and Amano, S}, title = {[A case of bilateral multiple primary breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {2036-2038}, pmid = {23267968}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/pathology/*surgery/therapy ; Carcinoma, Ductal, Breast/pathology/*surgery/therapy ; Combined Modality Therapy ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Neoplasms, Second Primary/pathology/*surgery/therapy ; Sentinel Lymph Node Biopsy ; }, abstract = {A 55-year-old woman underwent segmental resection and sentinel lymph node biopsy for cancer in her left breast 2.5 years ago. The pathological findings indicated papillotubular carcinoma [estrogen receptor-positive (ER+), progesterone receptor-positive(PgR+), and human epidermal growth factor receptor 2(HER2) score 0]. After the operation, she received adjuvant radiotherapy and endocrine therapy. Two and a half years after the operation, mammography revealed amorphous calcifications in her right breast. Stereotactic directional vacuum-assisted core-needle biopsy of the calcifications led to a diagnosis of invasive ductal carcinoma (ER+, PgR+, HER2 score 0). We performed quadrantectomy and sentinel lymph node biopsy. After the second operation, she received adjuvant radiotherapy and endocrine therapy with different modalities than used previously. Since the second operation, there has been no metastasis or recurrence.}, } @article {pmid23267937, year = {2012}, author = {Morioka, E and Ohno, Y and Noguchi, M and Nakano, Y and Noguchi, M and Kosaka, T and Takanaka, T}, title = {[Recurrent breast cancer obtained long-term survival with local treatment(surgery and stereotactic body radiotherapy)and systemic therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {12}, pages = {1942-1944}, pmid = {23267937}, issn = {0385-0684}, mesh = {Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Recurrence ; Time Factors ; }, abstract = {A 52-year-old woman developed right breast cancer and underwent modified radical mastectomy in 1994. Histologically, the tumor was invasive ductal carcinoma. She was positive for estrogen receptor (ER) but negative for progesterone receptor(PgR), while her human epidermal growth factor receptor type 2(HER2) status was not examined. Although she received adjuvant hormone therapy and chemotherapy[cyclophosphamide+doxorubicin+5-fluorouraci(l CAF), 6 courses ], she underwent partial pulmonary resection on both sides with right oophorectomy in 1997. Subsequently, she was treated with weekly doses paclitaxel(12 courses). However, she developed a pulmonary metastasis in the left breast. In 2002, she underwent a partial left pulmonary resection (ER-positive and HER2 3+) and treatment with an aromatase inhibitor. Subsequently, she was treated with trastuzumab because of repeated lung metastasis. A complete response was obtained after the administration of trastuzumab. In 2008, she developed bone metastasis in the sternum and the left seventh rib, and subsequently underwent stereotactic body radiotherapy (SBRT). She was treated with trastuzumab and aromatase inhibitor. At present, she is free of pain and is still living 15 years after breast cancer recurrence. This case suggests that the interaction of local treatment(surgery and SBRT) and systemic therapy(chemotherapy, hormonal therapy, and monoclonal therapy) may improve the survival of patients with recurrent breast cancer.}, } @article {pmid23267367, year = {2012}, author = {Jiang, Z and Zhou, Y and Devarajan, K and Slater, CM and Daly, MB and Chen, X}, title = {Identifying putative breast cancer-associated long intergenic non-coding RNA loci by high density SNP array analysis.}, journal = {Frontiers in genetics}, volume = {3}, number = {}, pages = {299}, pmid = {23267367}, issn = {1664-8021}, support = {P30 CA006927/CA/NCI NIH HHS/United States ; }, abstract = {Recent high-throughput transcript discoveries have yielded a growing recognition of long intergenic non-coding RNAs (lincRNAs), a class of arbitrarily defined transcripts (>200 nt) that are primarily produced from the intergenic space. lincRNAs have been increasingly acknowledged for their expressional dynamics and likely functional associations with cancers. However, differential gene dosage of lincRNA genes between cancer genomes is less studied. By using the high-density Human Omni5-Quad BeadChips (Illumina), we investigated genomic copy number aberrations in a set of seven tumor-normal paired primary human mammary epithelial cells (HMECs) established from patients with invasive ductal carcinoma. This Beadchip platform includes a total of 2,435,915 SNP loci dispersed at an average interval of ~700 nt throughout the intergenic region of the human genome. We mapped annotated or putative lincRNA genes to a subset of 332,539 SNP loci, which were included in our analysis for lincRNA-associated copy number variations (CNV). We have identified 122 lincRNAs, which were affected by somatic CNV with overlapped aberrations ranging from 0.14% to 100% in length. lincRNA-associated aberrations were detected predominantly with copy number losses and preferential clustering to the ends of chromosomes. Interestingly, lincRNA genes appear to be less susceptible to CNV in comparison to both protein-coding and intergenic regions (CNV affected segments in percentage: 1.8%, 37.5%, and 60.6%, respectively). In summary, our study established a novel approach utilizing high-resolution SNP array to identify lincRNA candidates, which could functionally link to tumorigenesis, and provide new strategies for the diagnosis and treatment of breast cancer.}, } @article {pmid23265123, year = {2012}, author = {Kapoor, NS and Chung, A and Huynh, K and Giuliano, AE}, title = {Preliminary results: double lumpectomies for multicentric breast carcinoma.}, journal = {The American surgeon}, volume = {78}, number = {12}, pages = {1345-1348}, pmid = {23265123}, issn = {1555-9823}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/pathology/surgery ; Carcinoma, Lobular/mortality/pathology/surgery ; Cohort Studies ; Databases, Factual ; Disease-Free Survival ; Female ; Humans ; Mastectomy, Segmental/*methods/mortality ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/mortality/pathology/*surgery ; Neoplasm Staging ; Neoplasms, Multiple Primary/mortality/pathology/*surgery ; Patient Selection ; Prognosis ; Retrospective Studies ; Risk Assessment ; Sentinel Lymph Node Biopsy/statistics & numerical data ; Survival Analysis ; Treatment Outcome ; }, abstract = {The standard operation for patients with multicentric breast cancer is total mastectomy. The safety of breast-conserving surgery (BCS) for these patients is unknown but interest in BCS has recently resurfaced as a result of the detection of occult second malignancies by breast magnetic resonance imaging (MRI). We report a small number of patients who chose to undergo "double lumpectomies," defined as two separate segmental mastectomies for primary cancers in different quadrants of the same breast. Patients with multicentric breast cancer surgically managed with double lumpectomies at our institute were identified retrospectively. Clinicopathologic features are described and outcomes reported. Seven patients underwent double lumpectomies for multicentric carcinoma. Median age was 69 years (range, 61 to 80 years). In five patients, MRI identified ipsilateral second malignancies. All patients had two foci of invasive carcinoma, all tumors expressed estrogen receptor, and none showed HER-2 overexpression. Tumor sizes ranged from 0.7 to 2.9 cm. Six patients had histologically distinct tumors in the same breast: five had one invasive lobular carcinoma (ILC) and one invasive ductal carcinoma (IDC), and one had classic ILC in one quadrant and pleomorphic ILC in another. One patient had two foci of IDC in separate quadrants. All patients had sentinel lymph node biopsies and none had nodal metastasis. Median follow-up was 26 months (range, 18 to 85 months). No patient developed locoregional recurrence. This small series suggests that "double lumpectomy" may be considered for multicentric invasive breast carcinoma in carefully selected patients with favorable tumors who desire breast conservation.}, } @article {pmid23264215, year = {2012}, author = {Grzegrzolka, J and Kurnol, K and Piotrow, P and Pula, B and Kobierzycki, C and Piotrowska, A and Jablonska, K and Wojnar, A and Rys, J and Dziegiel, P and Podhorska-Okolow, M}, title = {Hsp-27 expression in invasive ductal breast carcinoma.}, journal = {Folia histochemica et cytobiologica}, volume = {50}, number = {4}, pages = {527-533}, doi = {10.5603/16717}, pmid = {23264215}, issn = {1897-5631}, mesh = {Adult ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Female ; HSP27 Heat-Shock Proteins/*metabolism ; Heat-Shock Proteins ; Humans ; Middle Aged ; Molecular Chaperones ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; }, abstract = {The aim of this study was to determine the intensity of Hsp27 protein expression in fibrocystic breast changes (FC) and invasive ductal breast carcinoma (IDC) and to examine its impact on patients' clinico-pathological characteristics and overall survival. Immunohistochemical reactions were conducted on archival samples of 20 cases of FC and 101 cases of IDC treated in 1999-2002. Nuclear-cytoplasmic Hsp27 expression was observed in 92 (92.1%) of the examined cases of IDC, and all the cases of FC. Significantly higher Hsp27 expression was observed in G2 (p < 0.01) and G3 cases (p < 0.0001) compared to FC. HER-2 positive cases had higher Hsp27 expression (p = 0.0153), than HER-2 negative cases. Our research showed that Hsp27 could have an impact on tumor malignancy. Moreover, a positive correlation between the expression of Hsp27 and HER-2 positive cases was demonstrated.}, } @article {pmid23259792, year = {2013}, author = {Zhang, Y and Chen, Z and Bao, Y and Du, Z and Li, Q and Zhao, Y and Tang, F}, title = {Invasive neuroendocrine carcinoma of the breast: a prognostic research of 107 Chinese patients.}, journal = {Neoplasma}, volume = {60}, number = {2}, pages = {215-222}, doi = {10.4149/neo_2013_029}, pmid = {23259792}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Neuroendocrine/mortality/*pathology ; China ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; }, abstract = {Neuroendocrine carcinoma (NEC) of the breast, a distinct type of mammary carcinoma whose terminology was not proposed until 2003, has not been well recognized or studied. The aim of our study is to evaluate the clinicopathological features and outcomes of this type of tumor. We conducted a comparative study on 107 NEC patients and 475 invasive ductal carcinoma, not otherwise specified(IDC, NOS) patients from the Department of Pathology, Huashan Hospital, Fudan University, to determine the demographic, pathological, and clinical features at presentation, along with patient outcomes and prognostic factors. With an older age at presentation, NECs are more likely to be estrogen receptor(ER)/ progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER-2) negative, and have a higher propensity for local recurrence and poorer overall survival(OS). Higher T classification, M classification, TNM stage, the expression of Ki67, and the absence of PR expression are prognostically of poorer OS and distant recurrence-free survival(DRFS). Distant metastasis is also a dependent prognostic factor. NEC of the breast is a distinct type of neoplasm with higher malignancy. Novel therapies such as the endocrine therapy should be explored and studies with larger case number and longer follow-up will be needed.}, } @article {pmid23258771, year = {2013}, author = {Park, SH and Kim, EK and Park, BW and Kim, SI and Moon, HJ and Kim, MJ}, title = {False negative results in axillary lymph nodes by ultrasonography and ultrasonography-guided fine-needle aspiration in patients with invasive ductal carcinoma.}, journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)}, volume = {34}, number = {6}, pages = {559-567}, doi = {10.1055/s-0032-1313113}, pmid = {23258771}, issn = {1438-8782}, mesh = {Adult ; Aged ; Axilla ; *Biopsy, Fine-Needle ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology/surgery ; False Negative Reactions ; Female ; Humans ; Infant ; Lymph Nodes/*diagnostic imaging/*pathology ; Lymphatic Metastasis/*diagnostic imaging/*pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Preoperative Care ; Retrospective Studies ; *Ultrasonography, Interventional ; }, abstract = {PURPOSE: For preoperative evaluation of ALN status using various methods, axillary US and subsequent US-FNA targeting the LNs suspicious for metastasis are the most widely used methods. The purpose of our study was to assess the rate of false-negative results at preoperative ultrasonography (US) and ultrasonography guided fine needle aspiration (US-FNA) of axillary lymph nodes (ALNs) in breast cancer patients and the number of false-negative lymph nodes, and to evaluate factors related to ALN false negative results in US and/or US-FNA in patients diagnosed with invasive ductal carcinoma.

MATERIALS AND METHODS: Among 317 patients who underwent surgery for invasive ductal carcinoma during 2009 in Severance hospital, 237 patients had no reported ALN metastasis on preoperative US-FNA and US. We retrospectively reviewed the subsequent surgical pathology and clinicopathologic findings and assessed the rate of false-negative results from US and US-FNA of ALN and the number of false-negative lymph node. We performed univariate analysis and multivariate logistic regression analysis to evaluate the relationships between variable clinicopathologic factors (T-stage, position of ALN, hormone receptors, histologic grade, lymphovascular invasion (LVI) and performance of FNA) and cytologic results (false-negative result; FNALN and true negative result; TNALN) from US and/or US-FNA of ALN.

RESULTS: The rate of false-negative results was 42.4 % (59/139) in both US and US-FNA of ALN but among them, 57.6 % (34/59) showed only one metastatic ALN. Breast cancer with FNALN on US and US-FNA was significantly related to positive estrogen receptor (p = 0.003), positive progesterone receptor (p = 0.001), and the presence of LVI (p = 0.004) in univariate analysis. In multivariate analysis, high T stages (≥ T2, odds ratio (OR) 4.007, p = 0.004) and LVI (OR 7.951, p = 0.001) showed significant correlation with FNALN on US and US-FNA.

CONCLUSION: More than half of patients with FNALN showed only one metastatic ALN. LVI and high T-stages were the most important factors attributed to FNALN on US and US-FNA in patients with invasive ductal carcinoma.}, } @article {pmid23255773, year = {2013}, author = {Zheng, J and Alsaadi, T and Blaichman, J and Xie, X and Omeroglu, A and Meterissian, S and Mesurolle, B}, title = {Invasive ductal carcinoma of the breast: correlation between tumor grade determined by ultrasound-guided core biopsy and surgical pathology.}, journal = {AJR. American journal of roentgenology}, volume = {200}, number = {1}, pages = {W71-4}, doi = {10.2214/AJR.11.7461}, pmid = {23255773}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Large-Core Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; *Ultrasonography, Interventional ; }, abstract = {OBJECTIVE: The purpose of this article is to evaluate the concordance between tumor grade found on ultrasound-guided core biopsies of invasive ductal carcinomas of the breast and subsequent excision specimens.

MATERIALS AND METHODS: We retrospectively studied 300 consecutive invasive ductal carcinomas (274 women) that were biopsied under sonographic guidance, using 14-gauge core needles exclusively, and that were subsequently excised surgically. A minimum of four cores were taken per lesion. Core biopsy grades were compared with final surgical grades (reference standard). Tumor grade was assigned using the standard modified Scarff-Bloom-Richardson system. The agreement rate was expressed in percentages and in kappa statistics; the rates of overestimation and underestimation were also assessed. The correlation between tumor size (small, ≤ 0.5 cm; medium, 0.6-2.4 cm; and large, ≥ 2.5 cm) and agreement rate was also evaluated.

RESULTS: The overall agreement between core biopsy and surgical pathology grade was 69% (simple κ = 0.46; 95% CI, 0.36-0.54). Agreement by biopsy grade was 86% (55/64) for grade 3, 66% (118/180) for grade 2, and 55% (23/42) for grade 1. Core biopsy underestimated 24% (70/286) and overestimated 7% (20/286) of the lesions. When discordant, core biopsy differed from excision by no more than one grade. Large tumors were more likely to show underestimation rather than overestimation when discordant (rate of underestimation, 92% for large, 81% for medium, and 33% for small tumors; p < 0.0031).

CONCLUSION: Ultrasound-guided core biopsy accurately predicts high-grade breast tumors but is moderately accurate for lower-grade lesions. Large tumor size negatively impacts the accuracy of tumor grade found on biopsy and is associated with underestimation.}, } @article {pmid23250736, year = {2013}, author = {Pinto, AE and Pereira, T and Santos, M and Branco, M and Dias, A and Silva, GL and Ferreira, MC and André, S}, title = {DNA ploidy is an independent predictor of survival in breast invasive ductal carcinoma: a long-term multivariate analysis of 393 patients.}, journal = {Annals of surgical oncology}, volume = {20}, number = {5}, pages = {1530-1537}, doi = {10.1245/s10434-012-2804-6}, pmid = {23250736}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Aneuploidy ; Breast Neoplasms/*genetics/secondary/surgery ; Carcinoma, Ductal, Breast/*genetics/*pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *S Phase ; Time Factors ; Young Adult ; }, abstract = {PURPOSE: To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study.

METHODS: The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.

RESULTS: There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis.

CONCLUSIONS: Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.}, } @article {pmid23246269, year = {2013}, author = {Chen, AC and Paulino, AC and Schwartz, MR and Rodriguez, AA and Bass, BL and Chang, JC and Teh, BS}, title = {Prognostic markers for invasive micropapillary carcinoma of the breast: a population-based analysis.}, journal = {Clinical breast cancer}, volume = {13}, number = {2}, pages = {133-139}, doi = {10.1016/j.clbc.2012.10.001}, pmid = {23246269}, issn = {1938-0666}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/epidemiology/mortality/*pathology ; Carcinoma, Ductal, Breast/epidemiology/mortality/*pathology ; Carcinoma, Papillary/epidemiology/mortality/*pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Retrospective Studies ; SEER Program ; Survival Rate ; Texas/epidemiology ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare and distinct variant of breast carcinoma with a high propensity for regional lymph node involvement. Because of its lymphotropic nature, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC).

PATIENTS AND METHODS: This study of 624 patients diagnosed with breast IMPC (2001-2008) listed in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) database was performed to evaluate prognostic factors for disease-specific survival (DSS) and overall survival (OS).

RESULTS: The 5-year DSS and OS for patients with IMPC were 91.9% and 83.8%, respectively. Of those with known estrogen receptor (ER) status, 84.8% were ER-positive (ER(+)), which was associated with better DSS (hazard ratio [HR], 0.27; P < .0002) and OS (HR 0.45; P < .006). At presentation, 52.9% of the patients with lymph node examinations had nodal involvement and 4.1% had distant metastases. Patients with 4 or more positive lymph nodes had worse DSS (HR 6.43; P = .0013) and OS (HR 3.47; P = .00067) than did patients with node-negative disease, but those with 1 to 3 positive lymph nodes had DSS and OS similar to those of patients with node-negative disease.

CONCLUSION: Although IMPC has a high propensity for lymph node metastasis, it has a DSS and overall prognosis comparable to those of IDC. Patients with ER-negative (ER-) disease or those with 4 or more positive lymph nodes have the worst prognosis. This is the largest study of IMPC to date, and these findings will help address some of the inconsistencies regarding this rare histologic variant of breast cancer.}, } @article {pmid23245877, year = {2013}, author = {Dellapasqua, S and Maisonneuve, P and Viale, G and Pruneri, G and Mazzarol, G and Ghisini, R and Mazza, M and Iorfida, M and Rotmensz, N and Veronesi, P and Luini, A and Goldhirsch, A and Colleoni, M}, title = {Immunohistochemically defined subtypes and outcome of apocrine breast cancer.}, journal = {Clinical breast cancer}, volume = {13}, number = {2}, pages = {95-102}, doi = {10.1016/j.clbc.2012.11.004}, pmid = {23245877}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apocrine Glands/*pathology/surgery ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*classification/metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*classification/metabolism/mortality/pathology ; Carcinoma, Lobular/*classification/metabolism/mortality/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Recurrence, Local/metabolism/mortality/*pathology ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: Conflicting data are available in the literature on the outcome of invasive apocrine carcinoma (IAC), possibly related to a heterogeneous classification of these tumors.

PATIENTS AND METHODS: A series of 6899 consecutive patients with invasive ductal carcinoma (IDC) not otherwise specified and 72 patients with immunohistochemically defined IAC who received surgery at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence of IAC according to 2 immunohistochemically defined tumor subtypes: pure apocrine carcinoma (estrogen [ER] and progesterone [PgR] receptor negative, and AR positive) and apocrine-like carcinoma (ER or PgR positive and AR negative).

RESULTS: The diagnosis of pure apocrine carcinoma was correlated with a worse outcome in terms of DFS (hazard ratio [HR] 1.7; 95% confidence interval [CI], 1.01-2.86; P = .0010) if compared with IDC, whereas IDC and apocrine-like breast cancers showed a similar outcome in terms of DFS and overall survival. Patients with pure apocrine carcinoma had an increased risk in contralateral breast cancer (HR, 4.12; 95% CI, 1.22-14; P = .02).

CONCLUSION: Pure apocrine carcinoma represents a distinct subtype of breast cancer with a significantly worse DFS as compared with IDC. AR determination might have an important prognostic implication in IAC. Moreover, AR-targeted therapy should be further explored within these tumors.}, } @article {pmid23245275, year = {2013}, author = {Buchbender, S and Obenauer, S and Mohrmann, S and Martirosian, P and Buchbender, C and Miese, FR and Wittsack, HJ and Miekley, M and Antoch, G and Lanzman, RS}, title = {Arterial spin labelling perfusion MRI of breast cancer using FAIR TrueFISP: initial results.}, journal = {Clinical radiology}, volume = {68}, number = {3}, pages = {e123-7}, doi = {10.1016/j.crad.2012.10.011}, pmid = {23245275}, issn = {1365-229X}, mesh = {Adult ; Aged ; Analysis of Variance ; Biopsy ; Blood Flow Velocity ; Breast Neoplasms/*pathology/surgery ; Case-Control Studies ; Feasibility Studies ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Imaging, Three-Dimensional ; Magnetic Resonance Angiography/*methods ; Middle Aged ; Neovascularization, Pathologic/*pathology/surgery ; *Spin Labels ; }, abstract = {AIM: To assess the feasibility of an unenhanced, flow-sensitive, alternating inversion recovery-balanced steady-state free precession (FAIR TrueFISP) arterial spin labelling (ASL) magnetic resonance imaging (MRI) technique for quantification of breast cancer perfusion.

MATERIALS AND METHODS: Eighteen untreated breast tumour patients (mean age 53 ± 17 years, range 30-68 years) and four healthy controls (mean age 51 ± 14 years, range 33-68 years) were enrolled in this study and were imaged using a clinical 1.5 T MRI machine. Perfusion measurements were performed using a coronal single-section ASL FAIR TrueFISP technique in addition to a routine breast MRI examination. T1 relaxation time of normal breast parenchyma was determined in four healthy volunteers using the variable flip angle approach. The definitive diagnosis was obtained at histology after biopsy or surgery and was available for all patients.

RESULTS: ASL perfusion was successfully acquired in 13 of 18 tumour patients and in all healthy controls. The mean ASL perfusion of invasive ductal carcinoma tissue was significantly higher (88.2 ± 39.5 ml/100 g/min) compared to ASL perfusion of normal breast parenchyma (24.9 ± 12.7 ml/100 g/min; p < 0.05) and invasive lobular carcinoma (30.5 ± 4.3 ml/100 g/min; p < 0.05). No significant difference was found between the mean ASL perfusion of normal breast parenchyma and invasive lobular carcinoma tissue (p = 0.97).

CONCLUSION: ASL MRI enables quantification of breast cancer perfusion without the use of contrast material. However, its impact on diagnosis and therapy management of breast tumours has to be evaluated in larger patient studies.}, } @article {pmid23244108, year = {2012}, author = {Sofi, GN and Sofi, JN and Nadeem, R and Shiekh, RY and Khan, FA and Sofi, AA and Bhat, HA and Bhat, RA}, title = {Estrogen receptor and progesterone receptor status in breast cancer in relation to age, histological grade, size of lesion and lymph node involvement.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {10}, pages = {5047-5052}, doi = {10.7314/apjcp.2012.13.10.5047}, pmid = {23244108}, issn = {2476-762X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Carcinoma, Papillary/metabolism/pathology ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Young Adult ; }, abstract = {INTRODUCTION: Breast cancer is the most common malignancy of women in Kashmir. This study was conducted with the objective of assessing hormone receptor positivity and its correlation with age at diagnosis, tumor size, histological grade and lymph node metastasis.

MATERIALS AND METHODS: 132 newly diagnosed cases of invasive breast cancer diagnosed at the Department of Pathology, SKIMS, Srinagar, JandK, were included after excluding biopsies, in-situ lesions and recurrence cases.

RESULTS: Mean age of the patients was 48.2 years, 59.1% being ≤ 50 years of age. Mean duration of symptoms was 6.32 months. Most lesions (65.1%) were 2-5 cm and 16.7% were ≥ 5.0 cm in greatest dimension. The predominant (80.3%) morphology was IDC-NOS. The majority of the cases presented as grade II (52.1%) lesions and lymph node involvement was present in 65.2%. ER and PR were positive in 66.3% and 63.4% cases, respectively, increasing with rising age. High grade lesions and larger size tumors were more likely to be ER and PR negative. No correlation was found between ER/PR status and lymph node metastasis.

CONCLUSIONS: ER and PR expression in breast cancers in the current study was found to be higher than studies done in India/Asia but lower than studies conducted in the West, even on Indian/Asian immigrants. Markedly lower receptor expression in Indian/Asian studies is likely due to preanalytic variables, thresholds for positivity, and interpretation criteria. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer are strongly advocated for standardization of receptor evaluation and for clinical management of breast cancer patients to provide best therapeutic options.}, } @article {pmid23244096, year = {2012}, author = {Dogan, L and Gulcelik, MA and Yuksel, M and Uyar, O and Reis, E}, title = {Wire-guided localization biopsy to determine surgical margin status in patients with non-palpable suspicious breast lesions.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {10}, pages = {4989-4992}, doi = {10.7314/apjcp.2012.13.10.4989}, pmid = {23244096}, issn = {2476-762X}, mesh = {Biopsy, Needle/instrumentation ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/surgery ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {PURPOSE: Guide-wire localization (GWL) has been a standard technique for many years. Excision of non- palpable malignant breast lesions with clear surgical margins reduces the risk of undergoing re-excision. The objective of the present study was to evaluate the efficacy of GWL biopsy for assessing surgical margins.

METHODS: This retrospective study concerned 53 patients who underwent GWL biopsy for non-palpable breast lesions and breast carcinoma diagnosed by histological examination. Age of the patients, tumour size, radiographic findings, breast density specifications, specimen volumes, menopausal status and family history of the patients and surgical margin status were recorded.

RESULTS: Median age was 53.3 years, median tumour size was 1.5 cm and median specimen volume was 71.5 cm3. In fifteen patients (28%) DCIS and in 38 patients (72%) invasive ductal carcinoma was diagnosed. There was positive surgical margins in twenty eight (52.8%) patients. The median distance to the nearest surgical margin was 7.2 mm in clear surgical margins. Younger age and denser breast specifications were found as statistically significant factors for surgical margin status. Median age of the patients who had positive margins was 49.4 years where it was 56.9 years in the patients with negative margins (p=0.04). 79% of the patients with positive margins had type 3-4 pattern breast density according to BIRADS classification as compared to 48% in the patients who had negative margins (p=0.03). Some 38 patients who had positive or close surgical margins received re-excision (72%).

CONCLUSION: Positive margin rates may be higher because of inherent biological differences and diffuse growth patterns in younger patients. There are also technical difficulties that are relevant to denser fibroglandular tissue in placing hooked wire. High re-excision rates must be taken into consideration while performing GWL biopsy in non-palpable breast lesions.}, } @article {pmid23243536, year = {2012}, author = {Tural, D and Akar, E and Oztürk, T and Turna, H and Serdengeçti, S}, title = {Malignant clinical presentation of a benign granular cell tumor of breast in a patient with previously treated contralateral invasive ductal carcinoma.}, journal = {Case reports in oncological medicine}, volume = {2012}, number = {}, pages = {974740}, pmid = {23243536}, issn = {2090-6714}, abstract = {GCT is a rare neoplasm and usually shows the benign character. GCT can occur in any body site and may be multifocal. The most common involved site is tongue which accounts for nearly 30% of all cases but skin and subcutaneous tissue are also affected frequently. Breast is an unusually involved site and accounts for 6% of all GCTs. The histiogenesis of GCT is still controversial but further investigations and immunohistochemical examinations were exposed to neural origin and the tumor is thought to be derived from Schwann cells of peripheral nerves. Generally used technique to diagnose GCT is the positivity of S-100 immunohistochemical staining. Despite its benign nature, GCT may mimic breast carsinoma clinically and radiologically and easily be misdiagnosed for breast cancer. We herein report a case of granular cell tumor that arose in a 56 year-old female patient who previously had been treated from an invasive ductal carcinoma in contralateral breast.}, } @article {pmid23240012, year = {2012}, author = {Casanova, V and Naval-Macabuhay, I and Massanella, M and Rodríguez-García, M and Blanco, J and Gatell, JM and García, F and Gallart, T and Lluis, C and Mallol, J and Franco, R and Climent, N and McCormick, PJ}, title = {Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals.}, journal = {PloS one}, volume = {7}, number = {12}, pages = {e51287}, pmid = {23240012}, issn = {1932-6203}, mesh = {*Adenosine Deaminase/immunology/metabolism ; Adult ; Aged ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Differentiation/immunology ; Cell Proliferation ; Cells, Cultured ; Cytokines/immunology/metabolism ; *Dendritic Cells/cytology/immunology/metabolism ; Female ; *HIV Infections/immunology/metabolism/virology ; HIV-1/immunology/metabolism ; Humans ; *Immunity ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Receptors, Purinergic P1/immunology/metabolism ; }, abstract = {ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA-mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-α, CXCL8(IL-8), CCL3(MIP1-α), CCL4(MIP-1β) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.}, } @article {pmid23232912, year = {2013}, author = {Chakraborty, A and Mukhopadhyay, A and Bhattacharyya, D and Bose, CK and Choudhuri, K and Mukhopadhyay, S and Basak, J}, title = {Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India.}, journal = {Familial cancer}, volume = {12}, number = {3}, pages = {489-495}, pmid = {23232912}, issn = {1573-7292}, mesh = {Adult ; BRCA1 Protein/*genetics ; Breast Neoplasms/*congenital/epidemiology/genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/genetics/pathology ; Carcinoma, Lobular/epidemiology/genetics/pathology ; Case-Control Studies ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; India/epidemiology ; Middle Aged ; Mutation/*genetics ; Neoplasm Grading ; Neoplasm Invasiveness ; Ovarian Neoplasms/genetics/pathology ; Polymerase Chain Reaction ; Prognosis ; Young Adult ; }, abstract = {The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females pushing the cervical cancer to the second position. The mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, are frequently associated with familial breast cancer. The main objective of the study was to determine the frequency of the mutation 5382insC in BRCA1 of eastern Indian breast cancer patients and also study the hormonal receptor status and histopathology of the patients. Altogether 92 patients affected with breast cancer were included in this study. ARMS-PCR based amplification was used to detect the presence of mutation. The mutations were considered only after pedigree analysis. Out of 92 patients (age range: 20-77 years) with family history (57 individuals) and without family history (35 individuals) were screened. Fifty controls have been systematically investigated. Seven patients and two family members were found to be carriers of 5382insC mutation in BRCA1 gene. We have found 42.64 % ER(-)/PR(-) cancer and 20.58 % triple negative cancer. Invasive ductal carcinoma is the most common histology among the investigated individuals. The presented data confirm a noticeable contribution of BRCA1 5382insC mutation in BC development in Eastern India, which may justify an extended BRCA1 5382insC testing within this patient population. We found HER-2/neu negativity and BRCA1 positivity associated with familial breast cancer. From the hospital's patient history, it was revealed that the age of menarche plays an important role in development of breast cancer.}, } @article {pmid23228482, year = {2013}, author = {Kreb, DL and Looij, BG and Ernst, MF and Rutten, MJ and Jager, GJ and van der Linden, JC and Pruijt, JF and Bosscha, K}, title = {Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: lessons for further research.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {4}, pages = {543-547}, doi = {10.1016/j.breast.2012.11.004}, pmid = {23228482}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Catheter Ablation/*methods ; Cell Survival ; Feasibility Studies ; Female ; Humans ; In Vitro Techniques ; Mastectomy ; Mastectomy, Segmental ; Middle Aged ; Surgery, Computer-Assisted/*methods ; Treatment Outcome ; Ultrasonography, Interventional/methods ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: To assess the feasibility and effectiveness of radiofrequency ablation (RFA) in breast cancer, using different histopathologic staining methods to evaluate tissue viability.

MATERIALS AND METHODS: In twenty patients with unifocal small (≤1, 5 cm) invasive ductal carcinoma, ultrasound-guided RFA was performed immediately after surgery. Cell viability was assessed using cytokeratin 8 (CK 8) and nicotinamide adenine dinucleotide diaphorase (NADHD) in addition to hematoxylin-eosin (HE).

RESULTS: At histopathological examination, ex vivo RFA resulted in complete cell death of the target lesion in 17/20 patients. In two cases viable ductal carcinoma in situ (DCIS) was found just outside the completely ablated lesion.

CONCLUSION: RFA of small invasive breast cancer seems to be a feasible treatment option. Both NADHD and CK 8 demonstrate a clear and comparable demarcation between viable and non-viable tissue. A high level of accuracy is required in proper positioning of the needle electrode and a "hot retraction" is mandatory.}, } @article {pmid23227399, year = {2012}, author = {Yo, H and Ohashi, H and Inori, F and Okajima, Y and Matsui, Y and Shintani, K}, title = {Pseudoaneurysm Accompanied by Crowe Type IV Developmental Dysplasia of the Hip: A Case Report.}, journal = {Case reports in orthopedics}, volume = {2012}, number = {}, pages = {973489}, pmid = {23227399}, issn = {2090-6757}, abstract = {We report the case of a 72-year-old woman whose pseudoaneurysm was difficult to diagnose and treat. The patient had a history of congenital dislocated hip and was undergoing anticoagulation therapy with warfarin due to the mitral valve replacement. Her chief complaint was pain and enlargement of the left buttock, and the laboratory tests revealed severe anemia. However, her elderly depression confused her chief complaint, and she was transferred to a psychiatric hospital. Two months after the onset of the symptoms, she was finally diagnosed with a pseudoaneurysm by contrast-enhanced CT and angiography. IDC coils were used for embolization. A plain CT showed hemostasis as well as a reduced hematoma at 2 months after the embolization. The possible contributing factors for the pseudoaneurysm included bleeding due to warfarin combined with an intramuscular hematoma accompanied by Crowe type IV developmental dysplasia of the hip that led to an arterial rupture by impingement between pelvis and femoral head. Since the warfarin treatment could not be halted due to the valve replacement, embolization was chosen for her treatment, and the treatment outcome was favorable.}, } @article {pmid23222490, year = {2013}, author = {Lu, S and Singh, K and Mangray, S and Tavares, R and Noble, L and Resnick, MB and Yakirevich, E}, title = {Claudin expression in high-grade invasive ductal carcinoma of the breast: correlation with the molecular subtype.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {26}, number = {4}, pages = {485-495}, pmid = {23222490}, issn = {1530-0285}, support = {P20 GM103421/GM/NIGMS NIH HHS/United States ; P20GM103421/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Claudins/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Prognosis ; Proportional Hazards Models ; Tissue Array Analysis ; }, abstract = {Claudin proteins are a major component of the tight junctions. Dysregulation of claudin protein expression has been described in a number of malignancies. Gene expression profiling has stratified breast cancers into distinct molecular subtypes: luminal, HER2 positive (HER2+), and basal-like. Recently, a novel claudin-low molecular subtype has been described. In this study, we correlated the expression patterns of claudins with the molecular subtypes of breast cancer. On the basis of immunohistochemical expression, 226 grade 3 invasive ductal carcinomas were stratified into 65 luminal (estrogen receptor positive (ER+)), 65 HER2+, 86 basal-like, including 14 metaplastic carcinomas (ER-, HER2-, CK5/6, and/or epidermal growth factor receptor positive), and 10 unclassified. Tissue microarrays were analyzed for the expression of claudins 1, 3, 4, 7, and 8 by immunohistochemistry and scored semiquantitatively. High levels of expression were detected in 17% of all cases for claudin 1, 32% claudin 3, 41% claudin 4, 44% claudin 7, and 40% claudin 8. Luminal cancers exhibited increased claudins 7 and 8; basal-like tumors demonstrated increased expression of claudins 1 and 4. Low expression of all five claudins was detected in 30 of 226 cases (13%) and this group was designated 'claudin-low'. The majority of the claudin-low subgroup were basal-like cancers (23 of 30, 77%). In contrast, only 1 of 30 (3%) claudin-low tumors was of the luminal phenotype and 6 of 30 cases (20%) were HER2+ (P<0.001). Within the basal-like subgroup, 64% of the metaplastic and 19% of the non-metaplastic tumors were claudin-low. The claudin-low group was strongly associated with disease recurrence (P=0.0093). In conclusion, this study is the first to examine comprehensively the differential expression of claudins 1, 3, 4, 7, and 8 in the molecular subtypes of high-grade breast cancer. Claudin-low subtype is a frequent phenomenon in metaplastic and basal-like breast cancer and appears to be a strong predictor of disease recurrence.}, } @article {pmid23216911, year = {2012}, author = {Zhang, W and Gao, EL and Zhou, YL and Zhai, Q and Zou, ZY and Guo, GL and Chen, GR and Zheng, HM and Huang, GL and Zhang, XH}, title = {Different distribution of breast ductal carcinoma in situ, ductal carcinoma in situ with microinvasion, and invasion breast cancer.}, journal = {World journal of surgical oncology}, volume = {10}, number = {}, pages = {262}, pmid = {23216911}, issn = {1477-7819}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Postmenopause ; Premenopause ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast ductal cancer in situ (DCIS) can recur or progress to invasive ductal cancer (IDC), and the interim stage include DCIS with microinvasion (DCIS-Mi). In this article, we attempt to study the study the differences of clinicopathological features, imaging data, and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and IDC.

METHODS: In this retrospective study, we attempt to compare the clinicopathological features, immunohistochemical results and imaging data of 866 patients (included 73 DCIS, 72 DCIS-Mi, and 721 IDC).

RESULTS: Patients with DCIS and DCIS-Mi were younger than those with IDC (P = 0.007). DCIS and DCIS-Mi often happened in premenopausal women while IDC was opposite (P <0.001). The incidence of IDC with node-positive was significantly higher than it in DCIS and DCIS-Mi (P <0.001). We also observed that the Her2-positive was more often found in patients with pure DCIS compared to those with DCIS-Mi and DCIS-I (P <0.001). There was a significant difference between the four subgroups (Luminal-A, Luminal-B, ERBB2+, Basal-like) from DCIS, DCIS-Mi, and IDC (P <0.001). Basal-like patients were fewer than other subgroups in DCIS, DCIS-Mi, and IDC. The incidence of the first performance of ultrasound (catheter winded and nodular mass) and mammography (nodular mass) had significantly difference among patients with DCIS, DCIS-Mi, and IDC (P <0.001).

CONCLUSIONS: Different clinicopathological, immunohistochemical, and imaging features among DCIS, DCIS-Mi, and IDC indicate that they are distinct entities. A larger sample size is needed for further study.}, } @article {pmid23211565, year = {2013}, author = {Halperin, E and Porat, R and Tamir, M and Gross, JJ}, title = {Can emotion regulation change political attitudes in intractable conflicts? From the laboratory to the field.}, journal = {Psychological science}, volume = {24}, number = {1}, pages = {106-111}, doi = {10.1177/0956797612452572}, pmid = {23211565}, issn = {1467-9280}, mesh = {Adult ; Aggression/psychology ; Altruism ; Anger ; Arabs/psychology ; *Attitude ; *Cognition ; *Emotions ; Female ; Follow-Up Studies ; Humans ; Israel ; Jews/psychology ; Male ; *Negotiating ; *Politics ; Public Policy ; Social Identification ; }, abstract = {We hypothesized that an adaptive form of emotion regulation-cognitive reappraisal-would decrease negative emotion and increase support for conflict-resolution policies. In Study 1, Israeli participants were invited to a laboratory session in which they were randomly assigned to either a cognitive-reappraisal condition or a control condition; they were then presented with anger-inducing information related to the Israeli-Palestinian conflict. Participants in the reappraisal condition were more supportive of conciliatory policies and less supportive of aggressive policies compared with participants in the control condition. In Study 2, we replicated these findings in responses to a real political event (the recent Palestinian bid for United Nations recognition). When assessed 1 week after training, participants trained in cognitive reappraisal showed greater support for conciliatory policies and less support for aggressive policies toward Palestinians compared with participants in a control condition. These effects persisted when participants were reassessed 5 months after training, and at both time points, negative emotion mediated the effects of reappraisal.}, } @article {pmid23188444, year = {2012}, author = {Fota, GL and Stepan, A and Ciurea, RN}, title = {The evaluation of the immunoexpression of Her2÷neu oncoprotein in ductal carcinoma in situ in association with invasive ductal carcinoma of the breast.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {53}, number = {3 Suppl}, pages = {805-810}, pmid = {23188444}, issn = {2066-8279}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Middle Aged ; Oncogene Proteins ; Prognosis ; Receptor, ErbB-2/*biosynthesis ; }, abstract = {The identification of breast ductal carcinoma in situ (DCIS) is a factor that increases 8-10 times the risk of developing invasive ductal breast carcinoma (DCI) later. In this study, we evaluated the immunoexpression of the HER2/neu oncoprotein in the DCIS cases associated with DCI, both in situ and in the invasive components. We also studied the Her2/neu immunoreactivity in the cases of DCI having no DCIS association. The positive immunoreactivity (score 3) of the HER2/neu oncoprotein was present in 29 cases of high-grade DCIS having DCI associated, corresponding to the histological types comedo, solid, comedo/solid, and micropapillary. A weak-to-moderate complete membrane staining (score 2+) was determined in five high-grade DCIS and four intermediate-grade DCIS cases, belonging to the types comedo, solid, and micropapillary. The negative immunoreactivity of HER2/neu was identified in 18 cases, most of them being of low grade and belonging to the solid and cribriform types. The invasive component of the analyzed lesions indicated a HER2/neu positive reaction in 50% of lesions having DCI associated and 17.4% of the lesions having no DCIS association. The DCIS-DCI association and the DCIS histological types that were analyzed through the HER2/immunoexpression can stand as prognostic factors for the malignant breast lesions.}, } @article {pmid23188440, year = {2012}, author = {Pătrană, N and Georgescu, CV and Fota, GL and Enache, DE and Pirici, E}, title = {Invasive mammary carcinoma: assessment of HER-2/neu status by immunohistochemistry.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {53}, number = {3 Suppl}, pages = {781-787}, pmid = {23188440}, issn = {2066-8279}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*enzymology/*immunology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*metabolism ; }, abstract = {HER-2/neu oncoprotein overexpression in breast cancer patients has an impact on prognosis and treatment methods so assessment of its status is therefore much needed. The study group consisted of 90 cases of mammary invasive carcinoma. The distribution of HER-2/neu immunoexpression for scores 0, 1+, 2+ and 3+ were 54.44%, 11.11%, 18.8% and 15.56% respectively. HER-2/neu -positive cases comprised 21.42% of patients less than 50-year-old compared to 14.47% of patients of 50-year-old or older. Tumor size was negative correlated with HER-2/neu immunoexpression: positive tumors comprised 37.5% of tumor larger than 5 cm and this percentage decreases with tumor dimension to 2.94% in tumors of 2 cm or less. Regarding the histopathological subtype of invasive mammary carcinoma, only some types were positive, like 17.57% of IDC NOS and one case of mixed ductal-lobular invasive carcinoma. The highest proportion (21.31%) of positive HER-2/neu cases presented high-grade carcinomas (GIII), comparing with well-differentiated (GI) that were all negative. Regarding the axillary lymph node status the lowest proportion of positive HER-2/neu cases was 4.54% in the absence of metastasis, and rises to 34.78% in cases with more than three axillary lymph nodes involved. HER-2/neu-positive tumors showed a low incidence of ER+ or PR+ cases unlike HER-2/neu -negative cases (35.71% vs. 83.05% for ER, respective 21.42% vs. 76.27% for PR). Therefore, in conclusion, HER-2/neu-positive tumors are significantly fewer than the negative ones, but these are found in younger women and are associated with: large tumor size, high grade of malignancy (GIII) and increased number of axillary lymph node involvement. HER-2/neu immunoexpression is related to histological subtype of invasive breast carcinomas. Hormonal status is negative related to HER-2/neu expression.}, } @article {pmid23188432, year = {2012}, author = {Cotrutz, CE and Abuelba, H and Olinici, D and Petreuş, T}, title = {E-cadherin expression in invasive ductal carcinoma associates ultrastructural changes in desmosomes structure.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {53}, number = {3 Suppl}, pages = {731-734}, pmid = {23188432}, issn = {2066-8279}, mesh = {Breast Neoplasms/*metabolism/pathology ; Cadherins/*biosynthesis/metabolism ; Carcinoma, Ductal/*metabolism/pathology ; Desmosomes/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Paraffin Embedding ; }, abstract = {UNLABELLED: The relationship between E-cadherin presence/absence and the integrity of the desmosomes at the same level becomes important regarding the discrepancies between E-cadherin lack of expression in severe invasive carcinomas and the desmosome activity.

PURPOSE: In the present study, we have evaluated the presence of E-cadherin (EC) in 34 cases of metastatic or non-metastatic invasive ductal breast carcinomas (IDC) by immunohistochemistry followed by transmission electron microscopy (TEM) evaluation on samples prepared from paraffin sections.

MATERIALS AND METHODS: Our study has analyzed 34 paraffin blocks incoming from 20 cases with documented presence of metastatic invasion and 14 cases without metastases. All samples were processed and stained by classic Hematoxylin-Eosin, immunohistochemistry to detect EC presence and transmission electron microscopy.

RESULTS: Our results, even on a small pilot group, emphasize that EC presence is associated with the complete desmosomal integrity in non-metastatic cases, at least for the investigated areas. From the metastatic IDC cases, we have observed reduced EC expression in only three cases and important loss of desmosomal arrangement, mainly at the desmosomal plate level.

CONCLUSIONS: This observation can issue the hypothesis that even in IDC cells that express EC, the invasive potential depend not only on EC-dependent junctions but also on the desmosome integrity. Also, correlated relationship between EC expression, potentially explored desmogleins, desmocollin, desmoplakin and plakoglobin expression and TEM ultrastructure can lead to a conclusion about the invasive potential of these malignant cells.}, } @article {pmid23197249, year = {2013}, author = {Petrelli, F and Borgonovo, K and Lonati, V and Elia, S and Barni, S}, title = {Regression of liver metastases after treatment with intraperitoneal catumaxomab for malignant ascites due to breast cancer.}, journal = {Targeted oncology}, volume = {8}, number = {4}, pages = {291-294}, pmid = {23197249}, issn = {1776-260X}, mesh = {Aged ; Antibodies, Bispecific/*administration & dosage ; Ascites/*drug therapy/pathology ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology/secondary ; Female ; Humans ; Injections, Intraperitoneal ; Liver Neoplasms/*drug therapy/*secondary ; Treatment Outcome ; }, abstract = {Malignant ascites is quite rare in breast cancer and is mainly associated with a lobular histology. To date, no studies have evaluated locoregional therapy for malignant ascites in breast cancer. The anti-epithelial cell adhesion molecule (EpCAM), trifunctional antibody catumaxomab was approved in the European Union for the intraperitoneal (i.p.) treatment of malignant ascites in patients with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible. We report the case of a 69-year-old female with pretreated breast cancer who received i.p. catumaxomab for the treatment of malignant ascites and showed a regression of liver metastases. The patient originally underwent a left mastectomy and ipsilateral axillary lymph node dissection for an invasive ductal carcinoma in 1995. Following several lines of treatment, she was enrolled in February 2010 in a phase IIIb study (CASIMAS) investigating the safety of a 3-h i.p. catumaxomab infusion. In addition to a local benefit, as shown by an improvement in malignant ascites and a prolongation of the paracentesis-free interval with i.p. catumaxomab, a computed tomography scan, performed some weeks after catumaxomab administration, showed a regression of liver metastases. In addition to a locoregional effect on EpCAM-positive disease, i.p. catumaxomab may also show systemic effects. The use of i.p. catumaxomab for the treatment of malignant ascites due to breast cancer should be explored further in appropriate clinical studies and its possible systemic effects should also be further investigated.}, } @article {pmid23185163, year = {2012}, author = {Cuerda, S and Ramírez, N and Chara, L and Cassinello, J}, title = {New primary ipsilateral metachronous breast tumor: a case report.}, journal = {Case reports in oncology}, volume = {5}, number = {3}, pages = {580-585}, pmid = {23185163}, issn = {1662-6575}, abstract = {After breast-conserving treatment, the occurrence of ipsilateral breast tumor relapse raises the concern regarding whether it may represent two distinct types of lesion that it is important to define, a true recurrence (TR) or a new primary tumor (NPT). TR and NPT have different natural histories, prognosis, and in turn different implications for therapeutic management. We report the case of a 35-year-old woman who developed a breast invasive ductal carcinoma, which after receiving breast-conserving treatment with adjuvant chemotherapy, radiotherapy and hormone therapy, developed four years after an inflammatory carcinoma in the same breast, with different expression of immunohistochemical markers than the first breast cancer. The patient was treated with neoadjuvant chemotherapy that allowed the realization of a radical mastectomy with a complete pathological response. We describe the diagnostic and therapeutic approach of ipsilateral breast tumor relapses, along with a review of existing literature.}, } @article {pmid23184245, year = {2013}, author = {Wang, ZL and Li, JL and Li, M and Huang, Y and Wan, WB and Tang, J}, title = {Study of quantitative elastography with supersonic shear imaging in the diagnosis of breast tumours.}, journal = {La Radiologia medica}, volume = {118}, number = {4}, pages = {583-590}, pmid = {23184245}, issn = {1826-6983}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Area Under Curve ; Breast Neoplasms/*diagnostic imaging ; Diagnosis, Differential ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: This study was undertaken to evaluate the value of quantitative elastography in the diagnosis of breast tumours.

MATERIALS AND METHODS: Conventional ultrasound (US) and quantitative elastography were performed in 108 women with 114 breast lesions by two experienced radiologists, and pathological results were available in all cases. For each lesion, the maximum, mean, and minimum (min) elasticity and elasticity ratio between lesions and surrounding tissue were measured. The Breast Imaging Reporting and Data System (BI-RADS) categories were assessed with conventional US in all lesions.

RESULTS: Malignant lesions exhibited significantly higher maximum and mean elasticity (111.57 ± 69.29 kPa and 54.49 ± 33.70 kPa) than did benign lesions (59.00 ± 45.3 kPa and 36.64 ± 26.18 kPa) (p<0.01). For maximum elasticity versus BI-RADS, performance results were sensitivity 60.9 % vs. 78.3%, specificity 85.3% vs. 98.5%, positive predictive value (PPV) 73.7% vs. 97.3 %, negative predictive value (NPV) 76.3% vs. 87.0 % and accuracy 75.4% vs. 90.3%. BI-RADS had significantly better accuracy than maximum elasticity (p<0.01). Maximum and mean elasticity of invasive ductal carcinoma (IDC) were significantly higher than those of fibroadenoma (p<0.01), whereas the difference was not statistically significant with fibroadenosis, papilloma and inflammation (p>0.01). Maximum and mean elasticity and elasticity ratio of BI-RADS 5 were all significantly higher than those of BI-RADS 3 (p<0.01). Reliability for maximum and mean elasticity were almost perfect [intraclass correlation coefficients (ICC)=0.87 and 0.79].

CONCLUSIONS: Shear-wave elastography gives quantitative elasticity information that could potentially help in breast-lesion characterisation, although it cannot replace conventional BI-RADS in the differentiation of breast lesions.}, } @article {pmid23183846, year = {2012}, author = {Glenn, WK and Heng, B and Delprado, W and Iacopetta, B and Whitaker, NJ and Lawson, JS}, title = {Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e48788}, pmid = {23183846}, issn = {1932-6203}, mesh = {Aged ; Animals ; Base Sequence ; Breast Neoplasms/pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/virology ; Case-Control Studies ; Cell Nucleus/virology ; DNA, Neoplasm/genetics ; Epstein-Barr Virus Nuclear Antigens/metabolism ; Female ; Genome, Viral/genetics ; Herpesvirus 4, Human/*genetics ; Humans ; Lipopolysaccharide Receptors/metabolism ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Middle Aged ; Molecular Sequence Data ; Neoplasm Grading ; Neoplasm Invasiveness ; Papillomaviridae/*genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; Viral Matrix Proteins/metabolism ; }, abstract = {BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers.

MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc).

RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples.

CONCLUSIONS: We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.}, } @article {pmid23181716, year = {2012}, author = {Kostianets, O and Antoniuk, S and Filonenko, V and Kiyamova, R}, title = {Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {161}, pmid = {23181716}, issn = {1746-1596}, mesh = {Acid Anhydride Hydrolases ; Adult ; Aged ; Antigens, Neoplasm/analysis ; Autoantigens/*analysis ; Biomarkers, Tumor/*analysis ; Blood Proteins/analysis ; Breast Neoplasms/classification/*immunology/pathology ; Carcinoma, Ductal, Breast/classification/*immunology/pathology ; Carcinoma, Lobular/classification/*immunology/pathology ; Carcinoma, Medullary/classification/*immunology/pathology ; Carrier Proteins/analysis ; DNA Repair Enzymes/analysis ; DNA-Binding Proteins/analysis ; Female ; Fibrocystic Breast Disease/immunology/pathology ; Glycoproteins/analysis ; Humans ; *Immunohistochemistry ; Middle Aged ; Nuclear Proteins/analysis ; Pilot Projects ; Poly(A)-Binding Proteins/analysis ; RNA-Binding Proteins ; }, abstract = {BACKGROUND: On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer.

METHODS: Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five) was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples.

RESULTS: All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors.

CONCLUSIONS: This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy.

VIRTUAL SLIDES: The virtual slides' for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892.}, } @article {pmid23180247, year = {2013}, author = {Azordegan, N and Fraser, V and Le, K and Hillyer, LM and Ma, DW and Fischer, G and Moghadasian, MH}, title = {Carcinogenesis alters fatty acid profile in breast tissue.}, journal = {Molecular and cellular biochemistry}, volume = {374}, number = {1-2}, pages = {223-232}, pmid = {23180247}, issn = {1573-4919}, mesh = {Arachidonic Acid/metabolism ; Breast/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; *Cell Transformation, Neoplastic ; Docosahexaenoic Acids/metabolism ; Fatty Acids/*metabolism ; Female ; Humans ; Middle Aged ; Palmitic Acid/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Stearic Acids/metabolism ; }, abstract = {Cancerogenesis is associated with cell membrane changes. The aim of this study was to investigate whether breast tissues with different degrees of cancer involvement have different fatty acid profiles. Fourteen breast cancer patients with a mean age of 61 years were recruited. Morphological features of the tumoral specimens were characterized. Approximately 60 % of patients had invasive ductal carcinoma, and 80 % were ER positive; 65 % were PR positive; and 65 % were HER2 negative. The segments with confirmed cancer had significantly less amounts of total lipids as compared with the corresponding grossly normal or interface tissues. The fatty acid profile in cancer tissue was significantly different from that in other tissues. Fatty acid composition of five classes of phospholipids revealed the variations between cancer tissue and the other two segments. A transition of changes in fatty acid composition in these fractions of phospholipids was observed. The interface tissue had intermediate amounts of several fatty acids including palmitic acid, stearic acid, and arachidonic acid. Interestingly, we observed significantly higher amounts of the n-3 fatty acid DHA in cancer tissue as compared to the other two tissues. Data from this study will provide evidence that biochemical changes particularly phospholipid composition may take place well in advance prior to morphological changes. Should this theory be confirmed by larger studies, deviation of phospholipid composition from normal values can be used as markers of susceptibility of tissue to cancer development.}, } @article {pmid23175652, year = {2013}, author = {Remus, DM and Bongers, RS and Meijerink, M and Fusetti, F and Poolman, B and de Vos, P and Wells, JM and Kleerebezem, M and Bron, PA}, title = {Impact of Lactobacillus plantarum sortase on target protein sorting, gastrointestinal persistence, and host immune response modulation.}, journal = {Journal of bacteriology}, volume = {195}, number = {3}, pages = {502-509}, pmid = {23175652}, issn = {1098-5530}, mesh = {Aminoacyltransferases/genetics/*metabolism ; Animals ; Bacterial Proteins/genetics/*metabolism ; Cysteine Endopeptidases/genetics/*metabolism ; Dendritic Cells/immunology ; Gastrointestinal Tract/immunology/*microbiology ; Gene Deletion ; Gene Expression Regulation, Bacterial/*physiology ; Gene Expression Regulation, Enzymologic/physiology ; Humans ; Lactobacillus plantarum/*enzymology/genetics/immunology ; Membrane Proteins ; Mice ; Protein Transport/*physiology ; Transcriptome ; }, abstract = {Sortases are transpeptidases that couple surface proteins to the peptidoglycan of Gram-positive bacteria, and several sortase-dependent proteins (SDPs) have been demonstrated to be crucial for the interactions of pathogenic and nonpathogenic bacteria with their hosts. Here, we studied the role of sortase A (SrtA) in Lactobacillus plantarum WCFS1, a model Lactobacillus for probiotic organisms. An isogenic srtA deletion derivative was constructed which did not show residual SrtA activity. DNA microarray-based transcriptome analysis revealed that the srtA deletion had only minor impact on the full-genome transcriptome of L. plantarum, while the expression of SDP-encoding genes remained completely unaffected. Mass spectrometry analysis of the bacterial cell surface proteome, which was assessed by trypsinization of intact bacterial cells and by LiCl protein extraction, revealed that SrtA is required for the appropriate subcellular location of specific SDPs and for their covalent coupling to the cell envelope, respectively. We further found that SrtA deficiency did not affect the persistence and/or survival of L. plantarum in the gastrointestinal tract of mice. In addition, an in vitro immature dendritic cell (iDC) assay revealed that the removal of surface proteins by LiCl strongly affected the proinflammatory signaling properties of the SrtA-deficient strain but not of the wild type, which suggests a role of SDPs in host immune response modulation.}, } @article {pmid23172554, year = {2013}, author = {Ni, Y and Xie, X and Bu, H and Zhang, Z and Wei, B and Yin, L and Chen, M and Chen, H and Zhang, H}, title = {Concurrent primary angiosarcoma and invasive ductal carcinoma in the same breast.}, journal = {Journal of clinical pathology}, volume = {66}, number = {3}, pages = {263-264}, doi = {10.1136/jclinpath-2012-201233}, pmid = {23172554}, issn = {1472-4146}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnosis/metabolism/therapy ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/therapy ; Combined Modality Therapy ; Female ; Hemangiosarcoma/*diagnosis/metabolism/therapy ; Humans ; Neoplasms, Multiple Primary/*diagnosis/metabolism/therapy ; Treatment Outcome ; Ultrasonography, Mammary ; }, } @article {pmid23167359, year = {2012}, author = {Ch'ng, ES and Tuan Sharif, SE and Jaafar, H}, title = {Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {9}, pages = {4445-4452}, doi = {10.7314/apjcp.2012.13.9.4445}, pmid = {23167359}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antigens, CD34/metabolism ; Breast Neoplasms/*blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/*blood supply/metabolism/*secondary ; Chi-Square Distribution ; Cross-Sectional Studies ; Female ; Humans ; Lymphatic Metastasis ; Malaysia ; Microvessels/metabolism/*pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors.

METHODS: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density.

RESULTS: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05).

CONCLUSIONS: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.}, } @article {pmid23167341, year = {2012}, author = {Harhra, NA and Basaleem, HO}, title = {Trends of breast cancer and its management in the last twenty years in Aden and adjacent governorates, Yemen.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {9}, pages = {4347-4351}, doi = {10.7314/apjcp.2012.13.8.4247}, pmid = {23167341}, issn = {2476-762X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology/surgery ; Breast Neoplasms, Male/*epidemiology/pathology/surgery ; Carcinoma in Situ/*epidemiology/pathology/surgery ; Carcinoma, Ductal, Breast/*epidemiology/pathology/surgery ; Carcinoma, Lobular/*epidemiology/pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Male ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Yemen/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer of women and the principal cause of death in middle aged women. The objective of this study was to describe the trend of breast cancer and its management in Aden and adjacent south-eastern governorates of Yemen during the last 20 years.

PATIENTS AND METHODS: This is a retrospective analysis of previous studies on patients with breast cancer in Aden and adjacent south-eastern governorates, Yemen (January 1989 through December 2007). The studied variables were: sex, age, time and type of presentation, disease stage, pathological types and the performed surgical treatment. The sources of information were the treatment registry of Aden health office, archives of Al-Gamhouria teaching hospital; major referral and other public and private hospitals in Aden and Aden Cancer Registry.

RESULTS: The total number of patients was 476, 99% being females. The age range was 19-88 years. The most affected age was 30-50 years (60.5%), 95% presenting after one month of having breast symptoms. Forty-five percent presented with signs of advanced local disease, while 59.2% had palpable axillary lymph nodes on presentation. Early breast cancer (stages I-II) occurred in 47%, and late breast cancer (stages III-IV) in 51.5%. Invasive ductal carcinoma was the commonest pathology (89.3%). The main surgical treatment was mastectomy (modified radical mastectomy (50%).

CONCLUSION: Breast cancer is predominantly a disease of young with late presentation and advanced disease. Improving health awareness and earlier diagnosis of the disease by health education, encouraging breast self-examination, and providing the mammography equipment and mammary clinics in hospitals are recommended. Establishment of oncology and radiotherapy centers in Aden is a necessity.}, } @article {pmid23161115, year = {2013}, author = {Choi, DX and Eaton, AA and Olcese, C and Patil, S and Morrow, M and Van Zee, KJ}, title = {Blurry boundaries: do epithelial borderline lesions of the breast and ductal carcinoma in situ have similar rates of subsequent invasive cancer?.}, journal = {Annals of surgical oncology}, volume = {20}, number = {4}, pages = {1302-1310}, pmid = {23161115}, issn = {1534-4681}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/mortality/*pathology/surgery ; Carcinoma, Lobular/mortality/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/mortality/*pathology/surgery ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Survival Rate ; Young Adult ; }, abstract = {BACKGROUND: The histology of epithelial "borderline lesions" of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS.

METHODS: Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma.

RESULTS: A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.

CONCLUSIONS: When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite "borderline" histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.}, } @article {pmid23160758, year = {2013}, author = {Apostolidis, A and Thompson, C and Yan, X and Mourad, S}, title = {An exploratory, placebo-controlled, dose-response study of the efficacy and safety of onabotulinumtoxinA in spinal cord injury patients with urinary incontinence due to neurogenic detrusor overactivity.}, journal = {World journal of urology}, volume = {31}, number = {6}, pages = {1469-1474}, pmid = {23160758}, issn = {1433-8726}, mesh = {Adult ; Aged ; Aged, 80 and over ; Botulinum Toxins, Type A/adverse effects/pharmacology/*therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Spinal Cord Injuries/*complications ; Treatment Outcome ; Urinary Bladder, Neurogenic/*complications ; Urinary Bladder, Overactive/*complications ; Urinary Incontinence/*drug therapy/*etiology/physiopathology ; Urodynamics/drug effects/physiology ; }, abstract = {PURPOSE: To explore the dose response to onabotulinumtoxinA 50, 100, and 200 U in patients with spinal cord injury (SCI) with urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO).

METHODS: Patients (N = 73) with SCI (level T1 or lower) with NDO and UI (≥14 UI episodes/week) received 30 intradetrusor injections of onabotulinumtoxinA (50 U [n = 19], 100 U [n = 21], or 200 U [n = 17]) or placebo (n = 16) via cystoscopy, avoiding the trigone. Changes from baseline in UI episodes/week, volume voided/micturition, maximum cystometric capacity, and maximum detrusor pressure (MDP) during first involuntary detrusor contraction (IDC) were evaluated. Adverse events (AEs) were assessed.

RESULTS: A significant linear dose response for UI episodes/week was identified at weeks 18, 30, 36, 42, and 54 (P < 0.05) with a similar trend (P = 0.092) at week 6 (primary time point). A significant linear dose response was observed in volume/void at all post-treatment time points up to week 54 (P < 0.05) and in MDP during first IDC at week 6 (P = 0.034). The proportion of patients who achieved continence at week 6 was highest in the 200 U group. Duration of effect was longest with the 200 U dose, compared with other treatment groups. The AEs were comparable across groups; urinary tract infection was the most common AE across all treatment groups.

CONCLUSIONS: In this exploratory dose-response study of SCI patients with UI due to NDO, onabotulinumtoxinA 200 U was the most effective dose. The AE profile was comparable across all groups.}, } @article {pmid23158999, year = {2012}, author = {Yang, YF and Liu, J and Fang, ZY and Gu, L}, title = {[Clinical features and prognosis of 25 cases of breast carcinosarcoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {34}, number = {8}, pages = {620-623}, doi = {10.3760/cma.j.issn.0253-3766.2012.08.014}, pmid = {23158999}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/*therapy ; Carcinosarcoma/metabolism/*pathology/*therapy ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/secondary ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Tumor Burden ; }, abstract = {OBJECTIVE: To improve the recognition, appropriate diagnosis and treatment of breast carcinosarcoma through analysis of their clinical features, diagnosis, management and prognosis.

METHODS: The clinicopathological data from 25 patients with breast carcinosarcoma treated in our hospital between January 1976 and January 2008 were retrospectively reviewed. The correlation between prognosis and age, tumor size, axillary node status, and treatment modality was analyzed using the statistical software SPSS 13.0. The survival rate was calculated by Kaplan-Meier analysis and compared using log-rank test. Univariate and multivariate factors for survival were analyzed using Cox proportional hazards regression model.

RESULTS: All patients were female and their median age was 56-years. The median tumor diameter was 5.1 cm. The misdiagnosis rate was high by mammography, B-ultrasound and pathological examination of needle aspiration biopsy before operation. So that the diagnosis primarily depended on postoperative histopathologic examination. The ER/PR and HER-2 positive rate of the breast carcinosarcomas was 8.3% and 7.7%, respectively. Invasive ductal carcinoma was the main malignant component accounting for 92.3%, while the sarcoma element was constitutive of fibrosarcoma with a proportion of 46.2%. The overall 5-year survival rate was 57.9% with a median survival time of 86 months after a median follow-up of 52 months. Univariate factor analysis showed that the tumor size (P = 0.012) and treatment methods (P = 0.028) were impact factors, while age and axillary lymph node status were not significantly related with prognosis. Cox multivariate analysis validated that the therapy modality was an independent prognostic factor for breast carcinosarcoma (P = 0.047).

CONCLUSIONS: Breast carcinosarcoma is rare and its clinical features are not specific, so that its final diagnosis is mainly based on the postoperative pathology. Tumor size and treatment modality are independent prognostic factors, so the comprehensive therapy mainly based on radical resection is the best treatment modality. The positive expression of ER/PR and HER-2 in breast carcinosarcoma is low, while exploring new target is one of future research directions.}, } @article {pmid23157907, year = {2012}, author = {Sheng, WW and Zhou, JP and Kong, FM and Li, YJ and Dong, M}, title = {[Clinicopathological significance of the expression of carbonic anhydrase II in human pancreatic invasive ductal cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {50}, number = {8}, pages = {728-731}, pmid = {23157907}, issn = {0529-5815}, mesh = {Carbonic Anhydrase II/genetics/*metabolism ; Carcinoma, Pancreatic Ductal/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Pancreas/metabolism ; Pancreatic Neoplasms/metabolism/pathology ; RNA, Messenger/genetics ; }, abstract = {OBJECTIVE: To study the clinicopathological significance of the expression of carbonic anhydrase (CA)II protein and mRNA in primary invasive ductal cancer (IDC) of human pancreas.

METHODS: The expression of CAII protein in 33 paired paraffin embedded IDC specimens of the pancreas and paired adjacent non-cancerous pancreatic tissues was detected by immunohistochemistry. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to examine the expression of CAII protein and mRNA level in 12 paired fresh IDC specimens of the pancreas and adjuvant non-cancerous pancreatic tissues. The relationship between the protein expression and clinicopathological features was analyzed.

RESULTS: Overexpression of CAII protein was shown in 11 cases of pancreatic IDC tissues (33.3%, 11/33), which was much lower than that in paired non-cancerous pancreatic tissues (72.7%, t = 6.275, P = 0.000). The expression of CAII protein had no correlation with tumor position (χ² = 0.992, P = 0.319), differentiation (χ² = 0.866, P = 0.352), TNM stage (χ² = 1.210, P = 0.271) and Lymph node metastasis (χ² = 0.798, P = 0.372), but had bordering statistic sig with the prognosis of the patients (χ² = 3.233, P = 0.072). The median survival time in the patients with high expression of CAII protein was 540 days, while that in the patients with low expression was 320 days. The expression of CAII protein and mRNA was lower in IDC than that in paired non-cancerous pancreatic tissues detected by Western blot and RT-PCR respectively (t = 3.399, P = 0.006; t = 2.281, P = 0.043).

CONCLUSION: CAII is down regulated in pancreatic IDC and might be relative with the prognosis.}, } @article {pmid23155282, year = {2012}, author = {Watrowski, R and Striepecke, E and Jäger, C and Bauknecht, T and Horst, C}, title = {Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy after bilateral breast cancer.}, journal = {Anticancer research}, volume = {32}, number = {11}, pages = {5075-5078}, pmid = {23155282}, issn = {1791-7530}, mesh = {Adenocarcinoma, Papillary/*complications/*drug therapy/metabolism/surgery ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*complications/*drug therapy ; Carcinoma, Ductal, Breast/drug therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Second Primary/metabolism/*pathology/surgery ; Selective Estrogen Receptor Modulators/*therapeutic use ; Tamoxifen/*therapeutic use ; Uterine Cervical Neoplasms/*complications/metabolism/surgery ; }, abstract = {BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of cervical cancer. To our knowledge, this is the first report on PSCC of the uterine cervix following bilateral breast cancer.

CASE REPORT: A 61-year-old Caucasian woman underwent conserving surgery of both breasts at the age of 57 years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen treatment followed. Routine surveillance examinations, including pelvic examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were uneventful. Recently, a small contact-bleeding mass of the cervix was found. The Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159 U/ml. The patient was treated with radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0, V0, L0, was confirmed. According to the German recommendations for early-stage cervical cancer, the patient received no adjuvant treatment. Currently, the patient is free of relapse 38 months after the diagnosis of cervical cancer and 87 months after that of breast cancer.

CONCLUSION: Immunohistochemistry is helpful in diagnosing rare entities. This case adds further evidence that the prognosis for early-stage PSCC is probably not poorer than that for other cervical adenocarcinomas.}, } @article {pmid23149773, year = {2012}, author = {Abe, H and Shimauchi, A and Fan, X and River, JN and Sattar, H and Mueller, J and Karczmar, GS and Newstead, GM}, title = {Comparing post-operative human breast specimen radiograph and MRI in lesion margin and volume assessment.}, journal = {Journal of applied clinical medical physics}, volume = {13}, number = {6}, pages = {3802}, pmid = {23149773}, issn = {1526-9914}, mesh = {Adult ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology/surgery ; Female ; Humans ; *Magnetic Resonance Imaging ; Mastectomy, Segmental ; Middle Aged ; Postoperative Period ; Radiography ; }, abstract = {The purpose of this research is to evaluate the potential for identifying malignant breast lesions and their margins on large specimen MRI, in comparison to specimen radiography and clinical dynamic contrast enhanced MRI (DCE-MRI). Breast specimens were imaged with an MR scanner immediately after surgery, with an IRB-approved protocol and with the patients' informed consent. Specimen sizes were at least 5 cm in diameter and approximately 1 to 4 cm thick. Coronal and axial gradient echo MR images without fat suppression were acquired over the whole specimens using a 9.4T animal scanner. Findings on specimen MRI were compared with findings on specimen radiograph, and their volumes were compared with measurements obtained from clinical DCE-MRI. The results showed that invasive ductal carcinoma (IDC) lesions were easily identified using MRI and the margins were clearly distinguishable from nearby tissue. However, ductal carcinoma in situ (DCIS) lesions were not clearly discernible and were diffused with poorly defined margins on MRI. Calcifications associated with DCIS were visualized in all specimens on specimen radiograph. There is a strong correlation between the maximum diameter of lesions as measured by radiograph and MRI (r = 0.93), as well as the maximum diameter measured by pathology and radiograph/MRI (r>0.75). The volumes of IDC measured on specimen MRI were slightly smaller than those measured on DCE-MRI. Imaging of excised human breast lumpectomy specimens with high magnetic field MRI provides promising results for improvements in lesion identification and margin localization for IDC. However, there are technical challenges in visualization of DCIS lesions. Improvements in specimen imaging are important, as they will provide additional information to standard radiographic analysis.}, } @article {pmid23146856, year = {2012}, author = {Ahmed, M and Aurangzeb, and Pervez, A and Kamal, Z and Younas, A}, title = {Primary carcinoma of ectopic breast tissue in axilla.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {22}, number = {11}, pages = {726-727}, pmid = {23146856}, issn = {1681-7168}, mesh = {Adult ; Axilla/pathology ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymph Nodes/pathology ; Treatment Outcome ; }, abstract = {A 30 years old married lady presented with 4 x 5 cm, firm, non-tender, mobile swelling on anterior wall of left axilla. FNAC revealed carcinoma. The examination of breast including axillary tail, arm, chest and abdomen did not reveal any abnormality. Mammogram and MRI of both breasts did not reveal any lesion in the breast including axillary tail. Local wide excision along with axillary clearance was carried out. Final histopathology revealed invasive ductal carcinoma (Grade II) of axillary breast tissue and one, out of the recovered lymph nodes, was involved by the tumour. The immunohistochemistry also confirmed the findings.}, } @article {pmid23146383, year = {2012}, author = {Deb, S and Jene, N and , and Fox, SB}, title = {Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas.}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {510}, pmid = {23146383}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/metabolism ; BRCA2 Protein/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/*genetics/metabolism/pathology ; Cohort Studies ; *Genes, BRCA1 ; *Genes, BRCA2 ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunohistochemistry ; Male ; Microarray Analysis ; Middle Aged ; Mutation ; Phenotype ; Receptor, ErbB-2/genetics ; Survival Rate ; }, abstract = {BACKGROUND: Male breast cancer (MBC) is an uncommon and relatively uncharacterised disease accounting for <1% of all breast cancers. A significant proportion occurs in families with a history of breast cancer and in particular those carrying BRCA2 mutations. Here we describe clinicopathological features and genomic BRCA1 and BRCA2 mutation status in a large cohort of familial MBCs.

METHODS: Cases (n=60) included 3 BRCA1 and 25 BRCA2 mutation carries, and 32 non-BRCA1/2 (BRCAX) carriers with strong family histories of breast cancer. The cohort was examined with respect to mutation status, clinicopathological parameters including TNM staging, grade, histological subtype and intrinsic phenotype.

RESULTS: Compared to the general population, MBC incidence was higher in all subgroups. In contrast to female breast cancer (FBC) there was greater representation of BRCA2 tumours (41.7% vs 8.3%, p=0.0008) and underrepresentation of BRCA1 tumours (5.0% vs 14.4%, p=0.0001). There was no correlation between mutation status and age of onset, disease specific survival (DSS) or other clincopathological factors. Comparison with sporadic MBC studies showed similar clinicopathological features. Prognostic variables affecting DSS included primary tumour size (p=0.003, HR:4.26 95%CI 1.63-11.11), age (p=0.002, HR:4.09 95%CI 1.65-10.12), lymphovascular (p=0.019, HR:3.25 95%CI 1.21-8.74) and perineural invasion (p=0.027, HR:2.82 95%CI 1.13-7.06). Unlike familial FBC, the histological subtypes seen in familial MBC were more similar to those seen in sporadic MBC with 46 (76.7%) pure invasive ductal carcinoma of no special type (IDC-NST), 2 (3.3%) invasive lobular carcinomas and 4 (6.7%) invasive papillary carcinoma. A further 8 (13.3%) IDC-NST had foci of micropapillary differentiation, with a strong trend for co-occurrence in BRCA2 carriers (p=0.058). Most tumours were of the luminal phenotype (89.7%), with infrequent HER2 (8.6%) and basal (1.7%) phenotype tumours seen.

CONCLUSION: MBC in BRCA1/2 carriers and BRCAX families is different to females. Unlike FBC, a clear BRCA1 phenotype is not seen but a possible BRCA2 phenotype of micropapillary histological subtype is suggested. Comparison with sporadic MBCs shows this to be a high-risk population making further recruitment and investigation of this cohort of value in further understanding these uncommon tumours.}, } @article {pmid23144339, year = {2012}, author = {Mohamad, B and Iqbal, MN and Gopal, KV and Arshad, S and Daw, HA}, title = {Mai infection simulating metastatic breast cancer.}, journal = {BMJ case reports}, volume = {2012}, number = {}, pages = {}, pmid = {23144339}, issn = {1757-790X}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal/*diagnosis/therapy ; Female ; Granuloma/microbiology ; Humans ; Inflammation/microbiology ; Lung/*microbiology/pathology/surgery ; Lung Neoplasms/*diagnosis/secondary ; *Mycobacterium avium Complex ; Mycobacterium avium-intracellulare Infection/*diagnosis/drug therapy/microbiology ; }, abstract = {We represent a case of an asymptomatic female who was found to have a mass in the right breast which confirmed an invasive ductal carcinoma by core biopsy. After 3&emsp14;months of completion of chemo-radiotherapy, the patient remained totally asymptomatic. However, positron emission tomography scan showed four hypermetabolic lesions in the left lung thought to be consistent with metastatic disease. Standard uptake value ranged between 3.86 and 6; the results were consistent with metastatic breast cancer, so wedge resection was performed. Caseating granulomatous inflammation with necrosis was reported. Ultimately culture revealed Mycobacterium avium intracellulare infection. The lesions resolved completely after a course of antibiotics.}, } @article {pmid23141038, year = {2014}, author = {Lau, Y}, title = {Factors affecting the social problem-solving ability of baccalaureate nursing students.}, journal = {Nurse education today}, volume = {34}, number = {1}, pages = {121-126}, doi = {10.1016/j.nedt.2012.10.010}, pmid = {23141038}, issn = {1532-2793}, mesh = {China ; *Education, Nursing, Baccalaureate ; Humans ; *Problem Solving ; *Social Behavior ; Students, Nursing/*psychology ; Surveys and Questionnaires ; }, abstract = {The hospital environment is characterized by time pressure, uncertain information, conflicting goals, high stakes, stress, and dynamic conditions. These demands mean there is a need for nurses with social problem-solving skills. This study set out to (1) investigate the social problem-solving ability of Chinese baccalaureate nursing students in Macao and (2) identify the association between communication skill, clinical interaction, interpersonal dysfunction, and social problem-solving ability. All nursing students were recruited in one public institute through the census method. The research design was exploratory, cross-sectional, and quantitative. The study used the Chinese version of the Social Problem Solving Inventory short form (C-SPSI-R), Communication Ability Scale (CAS), Clinical Interactive Scale (CIS), and Interpersonal Dysfunction Checklist (IDC). Macao nursing students were more likely to use the two constructive or adaptive dimensions rather than the three dysfunctional dimensions of the C-SPSI-R to solve their problems. Multiple linear regression analysis revealed that communication ability (ß=.305, p<.0001), clinical interaction (ß=.129, p=.047), and interpersonal dysfunction (ß=-.402, p<.0001) were associated with social problem-solving after controlling for covariates. Macao has had no problem-solving training in its educational curriculum; an effective problem-solving training should be implemented as part of the curriculum. With so many changes in healthcare today, nurses must be good social problem-solvers in order to deliver holistic care.}, } @article {pmid23138139, year = {2012}, author = {Leong, LC and Gogna, A and Pant, R and Ng, FC and Sim, LS}, title = {Supplementary breast ultrasound screening in Asian women with negative but dense mammograms-a pilot study.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {41}, number = {10}, pages = {432-439}, pmid = {23138139}, issn = {0304-4602}, mesh = {Adult ; *Asian People ; Breast Neoplasms/*diagnostic imaging/ethnology ; Carcinoma, Ductal, Breast/*diagnostic imaging/ethnology ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/ethnology ; Early Detection of Cancer/*methods ; Female ; Follow-Up Studies ; Humans ; *Mammography ; Middle Aged ; Pilot Projects ; Prospective Studies ; Sensitivity and Specificity ; *Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: Dense breasts are common in Asian women and they limit the sensitivity of mammography. This study evaluates the performance of supplementary breast ultrasound screening in Asian women with dense mammograms.

MATERIALS AND METHODS: The study was approved by the hospital's Institutional Review Board. A prospective clinical trial was performed between September 2002 and November 2004. Asymptomatic Asian women with negative and dense mammograms were offered supplementary ultrasound screening for breast cancer. Ultrasound assessment was categorised as U1 to U4. U1 and U2 cases were recommended routine interval screening mammography. U3 cases were recommended follow-up ultrasound in 6 months and routine interval screening mammography and U4 cases were recommended biopsy.

RESULTS: One hundred and forty-one women with mean age of 45.1 years were enrolled into the study. Mean scan time was 13.0 minutes (± 5.6 minutes) for bilateral vs 11.0 minutes (± 1.4 minutes) for unilateral scans. There were 10 patients and 14 patients in the in the U3 and U4 categories, respectively. Two U4 category patients were diagnosed with malignancy-a-6 mm ductal carcinoma-in-situ and a 13- mm invasive ductal carcinoma. The breast cancer detection rate was 1.4%. Sensitivity and specifi city were 100% (2/2) and 88.5% (92/104) respectively. The positive predictive value was 14.3% (2/14) and the negative predictive value was 100% (92/92).

CONCLUSION: This pilot study reveals the usefulness of supplementary ultrasound screening in detecting early stage mammographically and clinically occult breast cancers in Asian women with dense breasts. A larger long-term study is, however, needed to assess its feasibility and impact on breast cancer prognosis.}, } @article {pmid23134301, year = {2012}, author = {Ghosh, S and De, S and Kakde, BN and Bhunia, S and Adhikary, A and Bisai, A}, title = {Intramolecular dehydrogenative coupling of sp2 C-H and sp3 C-H bonds: an expeditious route to 2-oxindoles.}, journal = {Organic letters}, volume = {14}, number = {23}, pages = {5864-5867}, doi = {10.1021/ol302767w}, pmid = {23134301}, issn = {1523-7052}, abstract = {An intramolecular-dehydrogenative-coupling (IDC) using "transition-metal-free" oxidation conditions has been achieved to synthesize a variety of 2-oxindoles bearing an all-carbon quaternary stereogenic center at the benzylic position. The methodology involves a one-pot C-alkylation of β-N-arylamido esters (3, 6) with alkyl halides using potassium tert-butoxide concomitant with a dehydrogenative coupling. A radical-mediated pathway has been tentatively proposed for the oxidative process.}, } @article {pmid23115007, year = {2013}, author = {Min, KW and Kim, DH and Do, SI and Pyo, JS and Kim, K and Chae, SW and Sohn, JH and Oh, YH and Kim, HJ and Choi, SH and Choi, YJ and Park, CH}, title = {Diagnostic and prognostic relevance of MMP-11 expression in the stromal fibroblast-like cells adjacent to invasive ductal carcinoma of the breast.}, journal = {Annals of surgical oncology}, volume = {20 Suppl 3}, number = {}, pages = {S433-42}, doi = {10.1245/s10434-012-2734-3}, pmid = {23115007}, issn = {1534-4681}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/enzymology/pathology ; Female ; Fibroblasts/*enzymology/pathology ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinase 11/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/enzymology/pathology ; Neoplasm Staging ; Prognosis ; Stromal Cells/*enzymology/pathology ; Tissue Array Analysis ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme known to be involved in the remodeling of extracellular matrix proteins. This enzyme recently has been reported to play a key role in tumor progression and results in poor clinical outcomes for several different types of tumors.

METHODS: A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were included in this study. MMP-11 expression in tumors and stromal fibroblast-like cells was analyzed by immunohistochemical staining on a tissue microarray. Subsequently, evaluation of the associations between MMP-11 expression and clinicopathological characteristics was performed.

RESULTS: MMP-11 expression of stromal fibroblast-like cells was correlated with prognostic factors, including tumor size, metastasis, histological grade, central tumor fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic markers, such as ER and HER2 (all p < 0.05). There was a significant relationship between worse overall survival and MMP-11 expression in both tumors and stromal fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression of stromal fibroblast-like cells was still significantly associated with poor prognosis (p = 0.043).

CONCLUSIONS: MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast.}, } @article {pmid23112116, year = {2013}, author = {de Beça, FF and Caetano, P and Gerhard, R and Alvarenga, CA and Gomes, M and Paredes, J and Schmitt, F}, title = {Cancer stem cells markers CD44, CD24 and ALDH1 in breast cancer special histological types.}, journal = {Journal of clinical pathology}, volume = {66}, number = {3}, pages = {187-191}, doi = {10.1136/jclinpath-2012-201169}, pmid = {23112116}, issn = {1472-4146}, mesh = {Adenocarcinoma/*metabolism/pathology ; Aldehyde Dehydrogenase 1 Family ; Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; CD24 Antigen/*metabolism ; Carcinoma, Medullary/metabolism/pathology ; Carcinoma, Papillary/metabolism/pathology ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Immunohistochemistry/methods ; Isoenzymes/*metabolism ; Metaplasia/metabolism/pathology ; Neoplastic Stem Cells/*metabolism/pathology ; Retinal Dehydrogenase/*metabolism ; }, abstract = {AIMS: CD44, CD24 and ALDH1 are the most consistently used biomarkers to identify and characterise the breast cancer stem cell (CSC) phenotype. However, most studies performed until now analysed samples of invasive ductal carcinomas of no special type (IDC-NST). Therefore, prevalence and clinical significance of these CSC markers in breast carcinomas of special histological types (SHT) is largely unknown. For that reason, this study aims to determine the distribution of the breast CD44, CD24 and ALDH1 CSC markers among a series of invasive breast carcinomas of SHT, in comparison with a series of IDC-NST.

METHODS: 117 invasive SHT breast carcinomas were analysed for the expression of CD44, CD24 and ALDH1, by immuhohistochemistry. The distribution of these CSC markers was evaluated among the distinct histological special types, and the results were compared with a series of 466 IDC-NST.

RESULTS: The expression prevalence of the breast CSC markers differed between special types and IDC-NST. Medullary, papillary and tubular carcinomas were enriched in the CSC phenotype CD44(+)/CD24(-/low) (80.0%, 100.0% and 100.0%, respectively, vs 45.3% in IDC-NST). Considering the ALDH1 cytoplasmic tumour expression, only medullary and metaplastic carcinomas displayed significant increase in CD44(+)/CD24(-/low)/ALDH1(+) CSC phenotype frequency (36.4% and 28.6%, respectively, vs 4.8% in IDC-NST).

CONCLUSIONS: The expression distribution of breast CSC markers is largely dependent on histological type. Interestingly, within the distinct SHT, medullary and metaplastic carcinomas are the two types highly associated with high-grade carcinomas, basal-like and claudin-low molecular subtypes, and to the CSC phenotype CD44(+)/CD24(-/low)/ALDH1(+).}, } @article {pmid23110022, year = {2012}, author = {Eom, M and Oh, SS and Lkhagvadorj, S and Han, A and Park, KH}, title = {HDAC1 Expression in Invasive Ductal Carcinoma of the Breast and Its Value as a Good Prognostic Factor.}, journal = {Korean journal of pathology}, volume = {46}, number = {4}, pages = {311-317}, pmid = {23110022}, issn = {2092-8920}, abstract = {BACKGROUND: Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance.

METHODS: We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates.

RESULTS: HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate.

CONCLUSIONS: HDAC1 expression is a good prognostic indicator in IDC.}, } @article {pmid23103133, year = {2013}, author = {Courtier, N and Gambling, T and Enright, S and Barrett-Lee, P and Abraham, J and Mason, MD}, title = {A prognostic tool to predict fatigue in women with early-stage breast cancer undergoing radiotherapy.}, journal = {Breast (Edinburgh, Scotland)}, volume = {22}, number = {4}, pages = {504-509}, doi = {10.1016/j.breast.2012.10.002}, pmid = {23103133}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/*complications/pathology/radiotherapy ; Carcinoma/*complications/pathology/radiotherapy ; Carcinoma, Ductal, Breast/complications/pathology/radiotherapy ; Carcinoma, Lobular/complications/pathology/radiotherapy ; Fatigue/*complications/diagnosis ; Female ; Humans ; Logistic Models ; Middle Aged ; Prognosis ; Risk Assessment/methods ; }, abstract = {BACKGROUND: Fatigue during and after radiotherapy impacts negatively on normal functioning and quality of life. A pre-treatment estimate of the risk of fatigue would facilitate the targeting of timely interventions to limit consequential behavioural symptoms arising. We have developed a prognostic tool to predict the risk of fatigue in women with early-stage breast cancer undergoing radiotherapy.

METHODS: Socio-demographic, clinical and self-reported characteristics were recorded for 100 women prescribed adjuvant radiotherapy for stages Tis-T2N1 breast cancer. Multiple logistic regression was used to develop a parsimonious prognostic model. The performance of the model when predicting fatigue for individuals not in the study was estimated by a leave-one-out cross-validation. A statistical weighting was assigned to the model variables to render a Fatigue Propensity Score of between 0 and 15. The ability of the Propensity Score to discriminate fatigued participants was estimated via receiver operating characteristic curve analysis.

RESULTS: 38% of participants reported significant fatigue during radiotherapy. Fatigue risk was predicted by elevated pre-treatment fatigue and anxiety, and diagnoses other than invasive ductal carcinoma (ductal carcinoma in-situ, invasive lobular and rarer carcinoma subtypes). The positive predictive value of the prognostic model was 80%. A Propensity Score threshold of ≥6 corresponded to a specificity of 90.3% and a sensitivity of 76.3%. The area under the receiver operating characteristic curve was 0.83 for the cross-validation sample.

CONCLUSIONS: Application of the Fatigue Propensity Score in the patient pathway can help direct fatigue management resources at those patients most likely to benefit.}, } @article {pmid23100210, year = {2012}, author = {Ulus, T and Yurtseven, E and Cavdar, S and Erginoz, E and Erdogan, MS}, title = {The suitability of using death certificates as a data source for cancer mortality assessment in Turkey.}, journal = {Croatian medical journal}, volume = {53}, number = {5}, pages = {480-485}, pmid = {23100210}, issn = {1332-8166}, mesh = {Cause of Death/trends ; Data Collection ; *Death Certificates ; Humans ; Neoplasms/*mortality ; Population ; Turkey/epidemiology ; }, abstract = {AIM: To compare the quality of the 2008 cancer mortality data of the Istanbul Directorate of Cemeteries (IDC) with the 2008 data of International Agency for Research on Cancer (IARC) and Turkish Statistical Institute (TUIK), and discuss the suitability of using this databank for estimations of cancer mortality in the future.

METHODS: We used 2008 and 2010 death records of the IDC and compared it to TUIK and IARC data.

RESULTS: According to the WHO statistics, in Turkey in 2008 there were 67255 estimated cancer deaths. As the population of Turkey was 71517100, the cancer mortality rate was 9.4 per 10000. According to the IDC statistics, the cancer mortality rate in Istanbul in 2008 was 5.97 per 10000.

CONCLUSION: IDC estimates were higher than WHO probably because WHO bases its estimates on a sample group and because of the restrictions of IDC data collection method. Death certificates could be a reliable and accurate data source for mortality statistics if the problems of data collection are solved.}, } @article {pmid23098574, year = {2013}, author = {Montagna, E and Maisonneuve, P and Rotmensz, N and Cancello, G and Iorfida, M and Balduzzi, A and Galimberti, V and Veronesi, P and Luini, A and Pruneri, G and Bottiglieri, L and Mastropasqua, MG and Goldhirsch, A and Viale, G and Colleoni, M}, title = {Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome.}, journal = {Clinical breast cancer}, volume = {13}, number = {1}, pages = {31-39}, doi = {10.1016/j.clbc.2012.09.002}, pmid = {23098574}, issn = {1938-0666}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*mortality/therapy ; Carcinoma, Ductal, Breast/metabolism/*mortality/therapy ; Carcinoma, Lobular/metabolism/*mortality/therapy ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Survival Rate ; }, abstract = {BACKGROUND: This study assesses outcome in terms of disease-free survival (DFS) and overall survival (OS) of special types of triple-negative breast cancer (TNBC).

PATIENTS AND METHODS: We identified 8801 women with first primary nonmetastatic breast cancer operated on at the European Institute of Oncology between 1997 and 2005. Of these patients, 781 consecutive patients with immunohistochemically defined TNBC were selected for the analyses. We explored patterns of recurrence by histologic type. Median follow-up was 5.7 years (range 0-13 years).

RESULTS: The 5-year DFS was 77% for TNBC, 68% for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and 84% and 95% for luminal B and luminal A breast cancer, respectively. From 781 TNBC subtypes, 693 cases (89%) were classified as ductal not otherwise specified (NOS) (invasive ductal carcinoma [IDC]), 29 were classified as apocrine (3.7%), 18 (2.3%) were classified as lobular, 10 (1.2%) were classified as adenoid cystic, and 10 (1.2%) were classified as metaplastic. Five-year DFS and OS were 77% and 84% for patients with ductal carcinoma, 56% and 89% for patients with metaplastic carcinoma, and both 5-year DFS and OS were 100% for patients with adenoid cystic and medullary carcinomas, respectively.

CONCLUSION: Distinct prognostic implications may derive from the specific histotype of TNBC. The identification of these special types has a significant clinical utility and should be considered in therapeutic algorithms.}, } @article {pmid23098509, year = {2012}, author = {Baloch, AH and Shuja, J and Daud, S and Ahmed, M and Ahmad, A and Tareen, M and Khan, F and Kakar, MA and Baloch, DM and Kakar, N and Naseeb, HK and Ahmad, J}, title = {Various aspects, patterns and risk factors in breast cancer patients of Balochistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {8}, pages = {4013-4016}, doi = {10.7314/apjcp.2012.13.8.4013}, pmid = {23098509}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*etiology/pathology ; Carcinoma, Ductal, Breast/epidemiology/*etiology/pathology ; Carcinoma, Lobular/epidemiology/*etiology/pathology ; Ethnicity ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Pakistan/epidemiology ; Prognosis ; Risk Factors ; Young Adult ; }, abstract = {PURPOSE: Breast cancer is the commonest malignancy of females throughout the world with one million new cases each year. In Pakistan, the burden of breast cancer disease is high with late stage presentation being a common feature, more than half being stage III or stage IV. The objective of this study was to study various aspects, patterns and risk factors in breast cancer patients of Balochistan.

METHOD: Present study was performed on 134 patients of breast cancer who were registered in CENAR. The patients were interviewed by providing a questionnaire. Informed consent was taken from all the patients who took part in this study after explanation of the study aims. Body mass index (BMI) was calculated andbiopsy reports were obtained from patients files. All the cases were classified with respect to age, gender, ethnic group (Baloch, Pashtoon, Punjabi, Afghani, Hazara) BMI, cancer type, cancer grade, hormonal status, side of the cancer, fertility and marital status.

RESULTS: Out of 134 patients, the most common ethnic group was Pashtoon with a total of 42 and the common age group was 41-50 years with a total of 51. Invasive ductal carcinoma (IDC) was the most common type, accounting for in 128 patients (95.5%) followed by invasive lobular carcinoma (ILC).

CONCLUSION: Pashtoon was the most common ethnic group, IDC was common type and most of the patients had an ER/PR positive hormonal status.}, } @article {pmid23046680, year = {2012}, author = {Loo, WY and Yue, Y and Fan, CB and Bai, LJ and Dou, YD and Wang, M and Liang, H and Cheung, MN and Chow, LW and Li, JL and Tian, Y and Qing, L}, title = {Comparing serum levels of cardiac biomarkers in cancer patients receiving chemotherapy and subjects with chronic periodontitis.}, journal = {Journal of translational medicine}, volume = {10 Suppl 1}, number = {Suppl 1}, pages = {S5}, pmid = {23046680}, issn = {1479-5876}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers/*blood ; Breast Neoplasms/*blood/*drug therapy ; Case-Control Studies ; Chronic Periodontitis/*blood ; Female ; Humans ; Inflammation Mediators/blood ; Male ; Middle Aged ; Myocardium/*metabolism ; Young Adult ; }, abstract = {BACKGROUND: Chronic periodontitis (CP) is a chronic inflammation associated with elevations of several inflammatory and cardiac markers. Studies implicated CP as one of the etiologies in coronary heart disease (CHD). Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU). The most severe cardiac complications are heart failure, arrhythmia and coronary heart disease (CHD). In this study, we compared the level of inflammatory factors and cardiac markers between chronic periodontitis patients and cancer patients receiving chemotherapy.

METHODS: 108 blood samples of periodontally healthy subjects were obtained on random from Hong Kong Red Cross, and these represented the controlled population. Forty-four patients diagnosed with chronic periodontitis were recruited from the West China Hospital of Stomatology, Sichuan University. They have received scaling and root planning with mean pocket depths of 6.05 mm. Thirty breast cancer patients diagnosed with invasive ductal carcinoma from UNIMED Medical Institute, Hong Kong gave consent to participate in this study. They received 4 cycles of 500mg/m2 5-fluorouracil, 75 mg/m2 epirubicin and 500mg/m2 cyclophosphamide at a 3-week interval between each cycle. Peripheral venous blood from each group was taken for measurement of blood cells, inflammatory marker (P-selectin, high sensitvity C-reactive protein) and cardiac markers (troponin T; troponin I; N-terminal pro brain natriuretic peptide (Nt-proBNP) and Lactate dehydrogenase (LDH).

RESULTS: The lymphocyte count was higher (p < 0.05) in periodontitis patients than the other two groups, and more neutrophils (p < 0.05) were seen in cancer patients receiving chemotherapy. The two test groups demonstrated higher levels (p < 0.01) of inflammatory and cardiac markers than the control group.

CONCLUSIONS: The elevated cardiac markers found in periodontitis patients suggested that they may carry potential risks in developing cardiac lesions. Troponin T, troponin I, pro-BNP, LDH and high sensitvity C-reactive protein may be used as markers to monitor cardiac lesions in chronic inflammatory patients.}, } @article {pmid23091544, year = {2012}, author = {Jung, SP and Lee, SK and Kim, S and Choi, MY and Bae, SY and Kim, J and Kim, M and Kil, WH and Cho, EY and Choe, JH and Kim, JH and Kim, JS and Nam, SJ and Lee, JE}, title = {Invasive pleomorphic lobular carcinoma of the breast: clinicopathologic characteristics and prognosis compared with invasive ductal carcinoma.}, journal = {Journal of breast cancer}, volume = {15}, number = {3}, pages = {313-319}, pmid = {23091544}, issn = {2092-9900}, abstract = {PURPOSE: Invasive pleomorphic lobular carcinoma (IPLC) is a very rare and distinct morphological variant of invasive lobular carcinoma (ILC), characterized by nuclear atypia and pleomorphism contrasted with the cytologic uniformity of ILC. This study evaluated clinicopathologic characteristics and prognosis of IPLC compared with invasive ductal carcinoma (IDC).

METHODS: We retrospectively reviewed the medical records of 35 patients with IPLC and 6,184 patients with IDC, not otherwise specified. We compared the clinicopathologic characteristics, relapse-free survival (RFS) and disease specific survival (DSS) of patients who were surgically treated between January 1997 and December 2010.

RESULTS: Patients with IPLC presented at an older age with larger tumor size, worse histologic grade, higher rates of N3 stage, more multifocal/multicentric tumors, and more nipple-areolar complex involvement than those of patients with IDC. During the follow-up period, the IPLC group experienced five cases (14.3%) of disease recurrence and three cases (8.6%) of disease specific mortality compared with 637 cases (10.4%) of recurrence and 333 cases (5.4%) of disease specific mortality in the IDC group. Univariate analysis using the Kaplan-Meier method revealed that the IPLC group showed a significantly poorer prognosis than that of the IDC group (RFS, p=0.008; DSS, p<0.001). However, after adjusting for clinicopathologic factors, a multivariate analysis showed no statistical differences in RFS (p=0.396) and DSS (p=0.168) between the IPLC and the IDC groups.

CONCLUSION: Our data suggest that patients with IPLC present with poor prognostic factors such as large tumor size, poor histologic grade and advanced stage at diagnosis. These aggressive clinicopathologic characteristics may result in poor clinical outcomes. Although our study could not link IPLC histology to poor prognosis, considering the aggressive characteristics of IPLC, early detection and considerate treatment, including proper surgical and adjuvant intervention, could be helpful for disease progression and survival.}, } @article {pmid23077461, year = {2012}, author = {Raeisi, E and Aghamiri, SM and Bandi, A and Rahmatpour, N and Firoozabadi, SM and Kafi-Abad, SA and Mir, LM}, title = {The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model.}, journal = {Radiology and oncology}, volume = {46}, number = {3}, pages = {226-232}, pmid = {23077461}, issn = {1581-3207}, abstract = {BACKGROUND: The aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice.

MATERIALS AND METHODS: Tumors of an average volume of 630 mm(3) were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates.

RESULTS: As anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy.

CONCLUSIONS: The results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses.}, } @article {pmid23077390, year = {2012}, author = {Barry, S and Ha, KY and Laurie, L}, title = {Carcinoma of the breast in men.}, journal = {Proceedings (Baylor University. Medical Center)}, volume = {25}, number = {4}, pages = {367-368}, pmid = {23077390}, issn = {1525-3252}, abstract = {Male breast cancer is an uncommon disease of uncertain etiology. We describe a 66-year-old man who presented with a palpable mass in the left breast with associated nipple inversion. Mammographic images demonstrated a spiculated mass within the subareolar left breast at the palpable area of concern. Sonographic evaluation demonstrated a hypoechoic mass within the subareolar left breast at the location of the mammographic abnormality. The patient underwent an excisional biopsy and was subsequently diagnosed with high-grade invasive ductal carcinoma, the most common histologic type of carcinoma identified in men.}, } @article {pmid23074114, year = {2012}, author = {Kim, SE and Koo, JS and Jung, WH}, title = {Immunophenotypes of glycogen rich clear cell carcinoma.}, journal = {Yonsei medical journal}, volume = {53}, number = {6}, pages = {1142-1146}, pmid = {23074114}, issn = {1976-2437}, mesh = {Adenocarcinoma, Clear Cell/*classification/*metabolism ; Breast Neoplasms/*classification/*metabolism ; ErbB Receptors/metabolism ; Female ; Glycogen/*metabolism ; Humans ; Immunohistochemistry ; Immunophenotyping/*methods ; Ki-67 Antigen/metabolism ; Proto-Oncogene Proteins c-kit/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {PURPOSE: Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.

MATERIALS AND METHODS: Here, we present three cases of GRCC and their immunohistochemical profiles.

RESULTS: Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).

CONCLUSION: In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.}, } @article {pmid23070345, year = {2012}, author = {Santos, GC and Góes, AC and Vitto, Hd and Moreira, CC and Avvad, E and Rumjanek, FD and Moura Gallo, CV}, title = {Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {67}, number = {10}, pages = {1181-1190}, pmid = {23070345}, issn = {1980-5322}, mesh = {Adult ; Age Distribution ; Aged ; Biomarkers, Tumor ; Brazil ; Breast Neoplasms/*genetics/pathology ; Carcinoma/*genetics/pathology ; Chromosomes, Human, Pair 13/*genetics ; Cohort Studies ; DNA, Mitochondrial/*genetics ; Female ; Genes, p53/genetics ; Genetic Loci/genetics ; Genomic Instability/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Microsatellite Repeats/genetics ; Middle Aged ; Neoplasm Grading ; }, abstract = {OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data.

METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions.

RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p= 0.0207).

CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness.}, } @article {pmid23062709, year = {2012}, author = {Joh, JE and Han, G and Kiluk, JV and Laronga, C and Khakpour, N and Lee, MC}, title = {Indications for axillary ultrasound use in breast cancer patients.}, journal = {Clinical breast cancer}, volume = {12}, number = {6}, pages = {433-437}, doi = {10.1016/j.clbc.2012.09.009}, pmid = {23062709}, issn = {1938-0666}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/*diagnostic imaging/pathology ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Predictive Value of Tests ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnostic imaging/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Ultrasonography, Mammary/*methods ; Young Adult ; }, abstract = {BACKGROUND: Axillary ultrasound has been adopted for preoperative planning in breast cancer. Our objective was to determine features predictive of abnormal AUS and/or positive axillary node needle biopsy (NBx).

MATERIALS AND METHODS: Single-institution database of breast cancer patients identified patients with preoperative AUS. Patient characteristics and outcomes were correlated with AUS and NBx. Significant features were identified using univariable and multivariable analysis and correlative statistics.

RESULTS: Three hundred thirteen breast cancers were evaluated. Abnormal AUS was demonstrated in 250 cases (80%). Node needle biopsy was performed in 247 cases (79%). Sensitivity and specificity was 93% and 48% for AUS and 86% and 100% for NBx, respectively. Palpable axillary adenopathy was significant in logistic regression model (P < .05). There were positive correlations between tumor grade, clinical T and tumor-node-metastasis stage, invasive ductal carcinoma histology, and inflammatory breast carcinoma with AUS and NBx (P < .05).

CONCLUSION: Clinicopathologic features (grade, histology, tumor size) might help guide judicious use of AUS.}, } @article {pmid23062488, year = {2012}, author = {Heselmeyer-Haddad, K and Berroa Garcia, LY and Bradley, A and Ortiz-Melendez, C and Lee, WJ and Christensen, R and Prindiville, SA and Calzone, KA and Soballe, PW and Hu, Y and Chowdhury, SA and Schwartz, R and Schäffer, AA and Ried, T}, title = {Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.}, journal = {The American journal of pathology}, volume = {181}, number = {5}, pages = {1807-1822}, pmid = {23062488}, issn = {1525-2191}, support = {R01 AI076318/AI/NIAID NIH HHS/United States ; 1R01AI076318/AI/NIAID NIH HHS/United States ; R01 CA140214/CA/NCI NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; 1R01CA140214/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosomal Instability/*genetics ; Clone Cells ; Disease Progression ; Female ; Genes, Neoplasm/genetics ; *Genetic Heterogeneity ; Genome, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Ploidies ; Proto-Oncogene Proteins c-myc/*genetics ; Single-Cell Analysis/*methods ; }, abstract = {Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.}, } @article {pmid23060565, year = {2012}, author = {Watanabe, K and Oochiai, T and Kikuchi, S and Kumano, T and Matsui, T and Morimoto, K and Yasukawa, S and Nakamori, S and Sasako, M and Yanagisawa, A and Otsuji, E}, title = {Dermokine expression in intraductal papillary-mucinous neoplasm and invasive pancreatic carcinoma.}, journal = {Anticancer research}, volume = {32}, number = {10}, pages = {4405-4412}, pmid = {23060565}, issn = {1791-7530}, mesh = {Adenocarcinoma, Mucinous/metabolism/*pathology ; Biomarkers, Tumor/analysis/*metabolism ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Carcinoma, Papillary/metabolism/*pathology ; Cell Line, Tumor ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Pancreatic Neoplasms/metabolism/*pathology ; Proteins/*metabolism ; }, abstract = {BACKGROUND: Serum dermokine (DK) is a novel biomarker for early colorectal cancer. To our knowledge this is the first study of DK expression in intraductal papillary mucinous neoplasm (IPMN) and pancreatic cancer.

MATERIALS AND METHODS: DK expression in human pancreatic cancer cell lines and tissues was assessed. We compared the sensitivities of common diagnostic markers, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), s-pancreas-1 antigen (SPAN-1), pancreatic cancer-associated antigen (DUPAN-2), and Nation Cancer Center-Stomach-439 (NCC-ST-439) in 26 patients with pancreatic neoplasms.

RESULTS: DK was expressed in pancreatic cancer cell lines. Immunohistochemical staining revealed that DK was expressed in atypical and cancerous tissues, but not in the normal pancreatic tissues. Serum DK was relatively high in patients with IPMN. The sensitivities of a serum multimarker test including DK was 76.5% (n=13/17) for IPMA/IPMC/invasive carcinoma derived from IPMN, and 100% (n=9/9) for ordinary invasive ductal carcinoma.

CONCLUSION: Serum DK is a potential biomarker in IPMN and invasive ductal carcinoma, when used in combination with conventional biomarkers.}, } @article {pmid23057431, year = {2012}, author = {Kinkor, Z and Sticová, E and Sach, J and Rychtera, J and Skálová, A}, title = {[Sarcomatoid (metaplastic) spindle cell carcinoma arising in a phylloid tumor with massive squamous metaplasia - a case report and review of the literature].}, journal = {Ceskoslovenska patologie}, volume = {48}, number = {3}, pages = {156-160}, pmid = {23057431}, issn = {1210-7875}, mesh = {Biomarkers, Tumor ; *Breast Neoplasms ; Carcinoma ; Humans ; *Immunohistochemistry ; Metaplasia ; }, abstract = {UNLABELLED: A 76-years-old woman underwent a partial mastectomy and a low-grade malignant homologous phyllodes tumor measuring 45 mm in maximum diameter was diagnosed. Beyond its typical dual composition the tumor displayed extensive intraductal squamous metaplasia. Approximately in one third of the lesion the original mesenchymal component cytologically and structurally changed which ultimately led to seeming stromal overgrowth. The loose storiform background contained isolated larger atypical elements with ample eosinophilic cytoplasm and obvious mitotic activity. This final fibromatosis-like arrangement was completed either by multiple dispersed abrupt squamous morules or just by pearl-like abortive form of squamous differentiation. Conventional in situ or invasive ductal carcinoma was not present. A combined expression of both low and high molecular weight cytoketatins, S100 protein, p63, CD10 and GFAP confirmed the incomplete basal/myoepithelial phenotype and ultimately led to the diagnosis of a spindle cell metaplastic carcinoma arising in a phyllodes tumor - a neoplasm unpublished so far. A review of the literature concerning epithelial malignancies originating from a milieu of phyllodes tumor guides discussion/speculation over the possible histopathogenesis of this vanishingly rare lesion.

KEYWORDS: breast - phylloid tumor - phyllodes tumor - spindle cell sarcomatoid/metaplastic carcinoma - squamous metaplasia.}, } @article {pmid23056988, year = {2012}, author = {Chern, J and Liao, L and Baraldi, R and Tinney, E and Hendershott, K and Germaine, P}, title = {Case report: ductal carcinoma in situ in the male breast.}, journal = {Case reports in radiology}, volume = {2012}, number = {}, pages = {532527}, pmid = {23056988}, issn = {2090-6870}, abstract = {High-grade ductal carcinoma in situ is incredibly rare in male patients. The prognosis for ductal carcinoma in situ (DCIS) in a male patient is the same as it would be for a female with the same stage disease; therefore, early recognition and diagnosis are of the utmost importance. We present a case of a male with unilateral invasive ductal carcinoma who was diagnosed with DCIS in the contralateral breast. The DCIS presented as microcalcifications on mammography and was found to be biopsy proven grade 3 papillary DCIS. This case also illustrates the importance of family history and risk factors, all of which need to be evaluated in any male presenting with a breast mass or nipple discharge.}, } @article {pmid23056525, year = {2012}, author = {Honda, K and Okusaka, T and Felix, K and Nakamori, S and Sata, N and Nagai, H and Ioka, T and Tsuchida, A and Shimahara, T and Shimahara, M and Yasunami, Y and Kuwabara, H and Sakuma, T and Otsuka, Y and Ota, N and Shitashige, M and Kosuge, T and Büchler, MW and Yamada, T}, title = {Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46908}, pmid = {23056525}, issn = {1932-6203}, mesh = {Adult ; Amino Acid Sequence ; Antibody Specificity ; Apolipoproteins/*blood/chemistry/immunology ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pancreatic Neoplasms/*blood ; Protein Multimerization ; Protein Structure, Quaternary ; Reproducibility of Results ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection.

METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1) using a newly developed matrix-assisted laser desorption/ionization (oMALDI) QqTOF (quadrupole time-of-flight) mass spectrometry (MS) system.

RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z), unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z), and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21), P = 4.35×10(-14), and P = 1.83×10(-24) (Mann-Whitney U-test); area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103) and Cohort 3 (n = 163)] and a prospective cohort [Cohort 4 (n = 833)] collected from 8 medical institutions in Japan and Germany.

CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.}, } @article {pmid23056178, year = {2012}, author = {Jones, DT and Lechertier, T and Mitter, R and Herbert, JM and Bicknell, R and Jones, JL and Li, JL and Buffa, F and Harris, AL and Hodivala-Dilke, K}, title = {Gene expression analysis in human breast cancer associated blood vessels.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e44294}, pmid = {23056178}, issn = {1932-6203}, support = {11359/CRUK_/Cancer Research UK/United Kingdom ; 12-1068/AICR_/Worldwide Cancer Research/United Kingdom ; 12007/CRUK_/Cancer Research UK/United Kingdom ; G0901609/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Angiogenesis Inhibitors/therapeutic use ; Animals ; Antibodies/immunology/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Aorta, Thoracic/drug effects/metabolism ; Bevacizumab ; Breast Neoplasms/blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/blood supply/*genetics/metabolism ; Cell Line, Tumor ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Microscopy, Confocal ; Neoplasms, Experimental/blood supply/drug therapy/genetics ; Neovascularization, Pathologic/drug therapy/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism ; RNA Interference ; Transplantation, Heterologous ; Tumor Burden/drug effects/genetics ; Vascular Endothelial Growth Factor A/genetics/immunology/pharmacology ; }, abstract = {Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold) in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC) of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of potentially novel anti-angiogenic targets that are likley to be, but not exclusivley, relevant to breast cancer.}, } @article {pmid23056033, year = {2012}, author = {Neema, S and Atuyambe, LM and Otolok-Tanga, E and Twijukye, C and Kambugu, A and Thayer, L and McAdam, K}, title = {Using a clinic based creativity initiative to reduce HIV related stigma at the Infectious Diseases Institute, Mulago National Referral Hospital, Uganda.}, journal = {African health sciences}, volume = {12}, number = {2}, pages = {231-239}, pmid = {23056033}, issn = {1729-0503}, mesh = {Adult ; Ambulatory Care Facilities ; Attitude of Health Personnel ; Creativity ; Cross-Sectional Studies ; Female ; Focus Groups ; HIV Infections/*psychology ; Health Education/*methods ; *Health Knowledge, Attitudes, Practice ; Hospitals ; Humans ; Male ; Middle Aged ; Qualitative Research ; Referral and Consultation ; Self Concept ; Sex Distribution ; *Social Networking ; *Social Stigma ; Socioeconomic Factors ; *Stereotyping ; Uganda ; }, abstract = {BACKGROUND: Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a major impact on public health interventions.

OBJECTIVES: The initiative was to provide activities in the clinic while patients waited to be seen by healthcare professionals. It was envisaged this would contribute to reduction of clinic based stigma felt by clients.

METHODS: This was a repeated cross-sectional survey (October-November 2005 and March-April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) at Mulago, the national referral hospital in Uganda. We utilized quantitative (survey) and qualitative (key informants, focus group discussions) methods to collect the data. Data were collected on stigma before the creativity initiative intervention was implemented, and a second phase survey was conducted to assess effectiveness of the interventions.

RESULTS: Clients who attended the IDC before the creativity intervention were about twice as likely to fear catching an infection as those who came after the intervention. The proportion that had fears to be seen by a friend or relative at the clinic decreased. Thus during the implementation of the Creativity intervention, HIV related stigma was reduced in this clinic setting.

CONCLUSIONS: The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ambiance at the clinic and clients became empowered, with creative, communication and networking skills. Improved knowledge and communication are key in addressing self stigma among HIV positive individuals.}, } @article {pmid23052813, year = {2013}, author = {Yoshinaga, Y and Enomoto, Y and Fujimitsu, R and Shimakura, M and Nabeshima, K and Iwasaki, A}, title = {Image and pathological changes after radiofrequency ablation of invasive breast cancer: a pilot study of nonsurgical therapy of early breast cancer.}, journal = {World journal of surgery}, volume = {37}, number = {2}, pages = {356-363}, pmid = {23052813}, issn = {1432-2323}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast/pathology/surgery ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/*surgery ; *Catheter Ablation ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Segmental ; Middle Aged ; Pilot Projects ; Treatment Outcome ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: The surgical treatment of early breast cancer has proceeded to less invasive approaches with better cosmetic results. The current study was undertaken to evaluate the clinical and pathological findings after radiofrequency ablation (RFA) without resection for a longer period of time.

METHOD: A total of 14 patients with breast cancer were enrolled. All patients were diagnosed to have invasive ductal carcinoma, and the median breast tumor size was 12 mm (range, 6-20 mm). Six patients received RFA treatment followed by immediate resection and eight patients without resection. The patients without resection were evaluated by ultrasound, MRI, and the pathological findings of a core needle biopsy after RFA. The removed specimens were examined by hematoxylin-eosin (HE) staining and nicotinamide adenine dinucleotide (NADH) diaphorase staining. The median follow-up of the patients was 39.9 months.

RESULTS: NADH staining was necessary to diagnose complete tumor cell death in the tissue for 3 months after RFA. However, HE staining alone could confirm the effect without NADH staining more than 6 months after RFA. Post-RFA, MRI scans clearly demonstrated the area as a complete ablated lesion in all patients without resection. The ablated area detected by MRI or ultrasound became gradually smaller. All patients that underwent RFA with no resection were alive without relapse.

CONCLUSION: RFA therefore could be an effective alternative to partial mastectomy for early breast cancer. Further research will be necessary to establish the standardization of the indications, as well as the optimal techniques and post treatment evaluation modalities.}, } @article {pmid23050179, year = {2012}, author = {Machalekova, K and Kajo, K and Bencat, M}, title = {Unusual occurrence of rare lipid-rich carcinoma and conventional invasive ductal carcinoma in the one breast: case report.}, journal = {Case reports in pathology}, volume = {2012}, number = {}, pages = {387045}, pmid = {23050179}, issn = {2090-679X}, abstract = {A 56-year-old woman noticed a palpable mass in her left breast during self-examination. Patient was admitted to our hospital and malignant bifocal tumour was diagnosed by ultrasonography, digital mammography, magnetic resonance, and core-cut biopsy. The patient underwent planned conservative surgery (biquadrantectomy) with a sentinel node examination, but after results of the frozen section with positive resection margins and positive sentinel lymph nodes subsequent mastectomy with axillary lymph node dissection were realized. Histology in the resection specimen revealed two isolated and distinct tumours. One of the lesions represented conventional invasive ductal carcinoma of histological grade 3, and the second tumour was evaluated as invasive lipid-rich carcinoma, containing tumour cells with clear and foamy cytoplasm. Lipids in neoplastic cells were detected by Oil Red O staining and ultrastructural examination. Immunohistochemical analysis of both carcinomas was almost identical with negative steroid receptors, positive staining of HER-2, and p53 and with high proliferation activity (Ki-67). Mastectomy specimen contained residual foci of invasive ductal carcinoma and dissected axillary lymph nodes were free of metastasis. Patient underwent first cycles of chemotherapy with paclitaxel and Herceptin together with local radiotherapy and two month after surgery is without any evidence of the disease.}, } @article {pmid23047180, year = {2012}, author = {Warbrick-Smith, J and Cawthorn, SJ}, title = {Sentinel lymph node biopsy following prior augmentation mammaplasty and implant rupture.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {65}, number = {12}, pages = {e348-50}, doi = {10.1016/j.bjps.2012.09.004}, pmid = {23047180}, issn = {1878-0539}, mesh = {Adult ; Axilla ; *Breast Implants ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Granuloma, Foreign-Body/diagnosis/*pathology/surgery ; Humans ; Mammography ; Mastectomy ; Neoplasm Invasiveness ; Prosthesis Failure ; *Sentinel Lymph Node Biopsy ; Silicones/adverse effects ; Tissue Expansion ; }, abstract = {We report the case of a 44 year old lady with bilateral cosmetic silicone breast implants who had previously undergone a change of her right implant following extracapsular rupture. She presented 4 years later with a new lump in her right breast and underwent subcutaneous mastectomy for a grade 3 invasive ductal carcinoma. Sentinel lymph node biopsy demonstrated axillary silicone lymphadenopathy but nil evidence of metastatic disease. We present this as the first described case of successful sentinel lymph node biopsy in the context of prior augmentation mammaplasty and ipsilateral implant rupture with silicone lymphadenopathy.}, } @article {pmid23042770, year = {2012}, author = {Frick, SU and Bacher, N and Baier, G and Mailänder, V and Landfester, K and Steinbrink, K}, title = {Functionalized polystyrene nanoparticles trigger human dendritic cell maturation resulting in enhanced CD4+ T cell activation.}, journal = {Macromolecular bioscience}, volume = {12}, number = {12}, pages = {1637-1647}, doi = {10.1002/mabi.201200223}, pmid = {23042770}, issn = {1616-5195}, mesh = {CD4-Positive T-Lymphocytes/*immunology ; Cytokines/immunology ; Dendritic Cells/drug effects/*immunology ; Humans ; Immunologic Factors/*chemistry/pharmacology ; Interferon-gamma/immunology ; Lymphocyte Activation/*drug effects ; Microscopy, Confocal ; Nanoparticles/*chemistry ; Organophosphonates ; Polystyrenes/*chemistry/pharmacology ; Sulfonic Acids ; }, abstract = {Nanoparticles (NP) represent a promising tool for biomedical applications. Here, sulfonate- and phosphonate-functionalized polystyrene NP are analyzed for their interaction with human monocyte-derived dendritic cells (DC). Immature dendritic cells (iDC) display a higher time- and dose-dependent uptake of functionalized polystyrene NP compared to mature dendritic cells (mDC). Notably, NP induce an enhanced maturation of iDC but not of mDC (upregulation of stimulatory molecules and cytokines). NP-triggered maturation results in a significantly enhanced T cell stimulatory capacity (increased CD4(+) T cell proliferation and IFN-γ production), indicating a shift to a pronounced Th1 response. Immunomodulatory properties of NP may be a useful strategy for strengthening the efficacy of NP-based approaches in immunotherapy.}, } @article {pmid23038687, year = {2013}, author = {Lee, S and de Boer, WB and Subramaniam, K and Kumarasinghe, MP}, title = {Pointers and pitfalls of mycophenolate-associated colitis.}, journal = {Journal of clinical pathology}, volume = {66}, number = {1}, pages = {8-11}, doi = {10.1136/jclinpath-2012-200888}, pmid = {23038687}, issn = {1472-4146}, mesh = {Acute Disease ; Adult ; Apoptosis/drug effects ; Biopsy ; Colitis/*chemically induced/diagnosis ; Colonoscopy ; Diagnosis, Differential ; Female ; Humans ; Immunosuppressive Agents/*adverse effects ; Intestinal Mucosa/*drug effects/pathology ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs & derivatives ; Organ Transplantation ; Postoperative Complications ; Retrospective Studies ; Young Adult ; }, abstract = {AIMS: Mycophenolate-associated colitis has been previously reported to show patterns of colonic mucosal injury mimicking a host of conditions, including graft-versus-host disease, ischaemia and inflammatory bowel disease (IBD). The aim of this study is to characterise, semiquantitatively, pathological changes of mycophenolate mofetil (MMF) mucosal injury.

METHODS: Seven transplant patients receiving MMF who underwent colonoscopic examination and biopsy were identified retrospectively over a 2-year period. Multiple histologic parameters, including architectural distortion, cryptitis, stromal active inflammation, individual damaged crypts (IDC) and crypt apoptotic figures were evaluated in the biopsies semiquantitatively. Where biopsy site was identified, the parameters were assessed separately in biopsies from right and left colon.

RESULTS: All cases showed mixed patterns of mucosal injury. All seven cases showed focal architectural distortion (in 58% of fragments per case), focal cryptitis (mean 3.0 foci per case), increased crypt apoptosis (mean 26.5/100 crypts) and IDC (mean 3.0 foci). Focal changes resembling acute self-limited colitis were noted in three cases. Possible proximal accentuation of some changes was noted with right side biopsies tending to show greater crypt apoptotic activity and more foci of architectural distortion. Three cases showed dual pathology (two with cytomegalovirus (CMV) infection and one with IBD).

CONCLUSIONS: Although a wide spectrum of changes may be seen in MMF-associated colitis, important microscopic clues include a mixed pattern of injury (typically a combination of crypt apoptosis, isolated crypt damage and architectural distortion), and possible proximal accentuation of pathologic changes. The need for clinical correlation and follow-up is emphasised by the occurrence of dual pathology in patients treated with MMF.}, } @article {pmid23035035, year = {2013}, author = {Raymond, AR and Norton, GR and Sareli, P and Woodiwiss, AJ and Brooksbank, RL}, title = {Relationship between average leucocyte telomere length and the presence or severity of idiopathic dilated cardiomyopathy in black Africans.}, journal = {European journal of heart failure}, volume = {15}, number = {1}, pages = {54-60}, doi = {10.1093/eurjhf/hfs147}, pmid = {23035035}, issn = {1879-0844}, mesh = {Adult ; Black People/*genetics ; Cardiomyopathy, Dilated/ethnology/*genetics/physiopathology ; Female ; Humans ; *Leukocytes ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Stroke Volume ; Telomere/*genetics ; *Ventricular Function, Left ; }, abstract = {AIMS: A reduced average leucocyte telomere length is associated with ischaemic heart failure. Whether this relationship represents a cause or consequence of heart failure or is attributed to associated risk factors and coronary artery disease is uncertain. We evaluated if average leucocyte telomere length is associated with idiopathic dilated cardiomyopathy (IDC) or its severity.

METHODS AND RESULTS: We compared average leucocyte telomere length in 223 patients with heart failure due to IDC and 227 healthy controls of black African ancestry. We also evaluated the relationship between average leucocyte telomere length and left ventricular ejection fraction (LVEF). LVEF was determined using echocardiography and radionuclide multiple-gated acquisition (MUGA) scan in patients with IDC. Relative leucocyte telomere length (T/S) was measured using a quantitative real-time polymerase chain reaction assay. Log T/S was negatively correlated with age in patients with IDC (P = 0.0007) and in controls (P = 0.030), and with alcohol consumption (P = 0.032) and regular smoking (P = 0.021) in patients with IDC. Log T/S did not differ between IDC and control groups either before (P = 0.11) or after (IDC = 0.071 ± 0.187, control = 0.071 ± 0.187, P = 0.99) adjustments for confounders. Log T/S was not associated with echocardiographic (P = 0.47) or MUGA (P = 0.99) LVEF or LV end-diastolic diameter (LVEDD) (P = 0.34) in patients with IDC. With adjustments for age, sex, alcohol consumption, and smoking, log T/S was similarly not associated with echocardiographic (P = 0.60) or MUGA (P = 0.91) LVEF or LVEDD (P = 0.53) in patients with IDC.

CONCLUSIONS: Average relative leucocyte telomere length is not associated with IDC or its severity in groups of black African ancestry.}, } @article {pmid23032626, year = {2012}, author = {Bellon, JR and Wong, JS and Burstein, HJ}, title = {Should response to preoperative chemotherapy affect radiotherapy recommendations after mastectomy for stage II breast cancer?.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {30}, number = {32}, pages = {3916-3920}, doi = {10.1200/JCO.2012.44.3358}, pmid = {23032626}, issn = {1527-7755}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Neoadjuvant Therapy/*methods ; Neoplasm Recurrence, Local/*diagnosis ; }, abstract = {A healthy 38-year-old woman presents with a palpable mass at the two o’clock position of the left breast. Mammography discloses a 3.2-cm spiculated lesion corresponding with the palpable abnormality, and ultrasonography confirms a solid mass in the breast and an enlarged, 2.1-cm lymph node with a thickened cortex in the ipsilateral axilla. Ultrasound-guided core needle biopsy of the breast mass diagnoses an invasive ductal carcinoma, poorly differentiated (grade 3), with lymphovascular invasion. Lymph node fine-needle aspiration is positive for malignant cells. Immunohistochemical studies on the breast specimen indicate that the tumor is triple negative, lacking estrogen and progesterone receptors and human epidermal growth factor 2 expression. The patient receives preoperative chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel. She has a dramatic clinical response; the breast and axillary masses shrink rapidly with chemotherapy. At the time of mastectomy, she is found to have several foci of residual invasive cancer in the breast (largest focus, 0.3 cm), located in a 3-cm tumor bed showing treatment effect (Figs 1A to 1C). The margins are negative, as are all 11 axillary lymph nodes. Her pathologic response to neoadjuvant treatment is judged Miller-Payne grade 4. She is referred for consideration of postmastectomy irradiation.}, } @article {pmid23032353, year = {2013}, author = {Nakash, O and Gerber, Y and Goldbourt, U and Benyamini, Y and Drory, Y and , }, title = {Ethnicity and long-term prognosis after myocardial infarction: a population-based cohort study.}, journal = {Medical care}, volume = {51}, number = {2}, pages = {137-143}, doi = {10.1097/MLR.0b013e318270bab5}, pmid = {23032353}, issn = {1537-1948}, mesh = {Aged ; Chi-Square Distribution ; Cohort Studies ; Comorbidity ; Educational Status ; Employment/statistics & numerical data ; Female ; Humans ; Incidence ; Income/statistics & numerical data ; Interviews as Topic ; Israel/epidemiology ; *Jews ; Male ; Middle Aged ; Myocardial Infarction/*ethnology/mortality/therapy ; Prognosis ; Proportional Hazards Models ; Residence Characteristics ; Risk Factors ; Social Class ; Treatment Outcome ; }, abstract = {BACKGROUND: Health disparities are systematic differences in health, favoring members of advantaged over disadvantaged groups in the society. This study examines the contribution of multiple socioeconomic status (SES) measures to ethnic differences in after myocardial infarction (MI) prognosis.

METHODS: Patients aged 65 years and younger (n=1040) belonging to Ashkenazi and Mizrahi advantaged and disadvantaged ethnic groups discharged from 8 hospitals in central Israel after incident MI in 1992-1993, were followed up through 2005 for all-cause mortality, recurrent MI, heart failure, and ischemic stroke.

RESULTS: Advantaged Ashkenazi had higher education, income, employment, and neighborhood SES compared with disadvantaged Mizrahi. Cardiovascular risk factors varied among the different ethnic groups. Results showed that the association between ethnic group and all outcomes differed substantially between models that included a single SES measure and those that included multiple measures. For example, the hazard ratio for mortality in disadvantaged Mizrahi compared with advantaged Ashkenazi was 1.87 [95% confidence interval (CI), 1.40-2.48] in a model adjusting only for demographic variables; 1.58 (95% CI, 1.18-2.12) in a model adjusting also for income; and 1.03 (95% CI, 0.74-2.04) in a model adjusting for all measured SES indicators. Further adjustment for clinical variables did not appreciably change the results.

CONCLUSIONS: Findings show that a wide array of modifiable social factors shaped by income, education, and neighborhood socioeconomic conditions can explain ethnic health differences and highlight the importance of using multivariable models of SES.}, } @article {pmid23031786, year = {2013}, author = {Lin, H and Huang, JF and Qiu, JR and Zhang, HL and Tang, XJ and Li, H and Wang, CJ and Wang, ZC and Feng, ZQ and Zhu, J}, title = {Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer.}, journal = {Experimental and molecular pathology}, volume = {94}, number = {1}, pages = {73-78}, doi = {10.1016/j.yexmp.2012.08.004}, pmid = {23031786}, issn = {1096-0945}, mesh = {Antigens, Neoplasm/*biosynthesis/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology/therapy ; Cell Adhesion Molecules/*biosynthesis/genetics ; Cyclin D1/*biosynthesis/genetics ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Up-Regulation ; }, abstract = {The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P<0.001 and P=0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ(2) test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P=0.023), P53 status (P=0.042), Cyclin D1 status (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.004) and TNM staging (P<0.001). Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.}, } @article {pmid23021868, year = {2012}, author = {Rua, C and Lebas, P and Michenet, P and Ouldamer, L}, title = {Evaluation of lumpectomy surgical specimen radiographs in subclinical, in situ and invasive breast cancer, and factors predicting positive margins.}, journal = {Diagnostic and interventional imaging}, volume = {93}, number = {11}, pages = {871-877}, doi = {10.1016/j.diii.2012.07.010}, pmid = {23021868}, issn = {2211-5684}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/*surgery ; Female ; Fiducial Markers ; Humans ; Mammography/*methods ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Neoplasm, Residual/*diagnosis/*pathology ; Prognosis ; Radiographic Image Enhancement/*methods ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: To determine the diagnostic performance of radiological evaluation of the margins of surgical specimens from lumpectomies for subclinical malignant breast lesions.

MATERIALS AND METHODS: Retrospective study in two French hospitals including all patients who had a non-palpable in situ (ISDC) or invasive (IDC) ductal carcinoma treated by lumpectomy after radiological localisation. For the analysis, the lesions were divided into two groups depending on the majority component in the definitive histological examination: ISDC or IDC. The radiological margin considered was 10mm.

RESULTS: For the 178 lumpectomies studied, the sensitivity of the radiographs of the surgical specimen was 33.3% for ISDC and 50% for IDC. The surgical revision rate was 27.41% for ISDC and 12.64% for IDC. The significant predictive factors for positive margins were the radiological size of the lesions (>10mm) for ISDC (P=0.02) and radiologically positive margins for IDC (P=0.01). Correlation was found between the histological and radiological sizes of the lesion for IDC, but not for ISDC.

CONCLUSION: Radiological examination of surgical specimens does not provide a satisfactory evaluation of the histological margins, in particular for ISDC, even with a radiological threshold of 10mm.}, } @article {pmid23020285, year = {2013}, author = {Jing, X and Wey, E and Michael, CW}, title = {Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {24}, number = {6}, pages = {372-376}, doi = {10.1111/cyt.12022}, pmid = {23020285}, issn = {1365-2303}, mesh = {Axilla/*pathology ; Biopsy, Fine-Needle/methods ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*pathology ; Cytodiagnosis ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Predictive Value of Tests ; Sentinel Lymph Node Biopsy ; }, abstract = {OBJECTIVE: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma.

METHODS: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto-histologically discrepant cases were reviewed.

RESULTS: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom-Richardson grade or the number or size of metastases between tumours with true-positive and false-negative cytology. Sampling error was the sole factor contributing to cyto-histological discrepancy.

CONCLUSIONS: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.}, } @article {pmid23017667, year = {2012}, author = {Madeira, KP and Daltoé, RD and Sirtoli, GM and Rezende, LC and Carvalho, AA and Guimarães, Idos S and Silva, IV and Rangel, LB}, title = {Comparison of immunohistochemical analysis with estrogen receptor SP1 and 1D5 monoclonal antibodies in breast cancer.}, journal = {Pathology, research and practice}, volume = {208}, number = {11}, pages = {657-661}, doi = {10.1016/j.prp.2012.07.010}, pmid = {23017667}, issn = {1618-0631}, mesh = {Adenocarcinoma/*diagnosis ; *Antibodies, Monoclonal ; Biomarkers, Tumor/*immunology ; Breast Neoplasms/*diagnosis ; Estrogen Receptor alpha/*immunology ; Female ; Humans ; Immunohistochemistry/methods ; Reproducibility of Results ; Tissue Array Analysis ; }, abstract = {In the present study, we aimed to evaluate estrogen receptor ER-alpha status in 61 breast cancer cases using Sp1 and 1D5 monoclonal antibodies. Tissue array platforms were generated containing samples of breast cancer and positive controls that were assayed by immunohistochemistry applying monoclonal primary antibodies anti-ER alpha, SP1 and 1D5. We noted a high concordance rate (96.7%) between the referred antibodies. Moreover, we calculated the Kappa factor (0.921), indicating that 1D5 and SP1 provided overlapping ERα expression results. Indeed, we observed controversial results only in 2 samples studied, which were ER-negative when stained with 1D5 and ER-positive when assessed with SP1. Total concordance of PS was obtained (Pearson and intraclass CF, 0.7351 and 0.6193, respectively). However, concordance between the antibodies seems to be more accurate in higher PS values. An excellent IS correlation between antibodies was observed throughout the population (Spearman's CF, ρ=0.9150). Following the Allred score, 17 out of 42 positive BC samples diverged, with 1D5 always pointing to weaker staining than SP1. When calculating Spearman's CF of Total Score (TS) within the population, an excellent correlation between both the antibodies (ρ=0.9238) was noted. Nonetheless, the results were less concordant among the BC-positive cases (ρ=0.7743). Indeed, 20 samples were differentially classified using the antibodies (only 3 had higher TS with 1D5). Considering the mean TS of all samples or of invasive ductal carcinoma, SP1 provided higher scores than 1D5 (p<0.05). We recommend the use of the anti-ER RMAb SP1 due to the high probability that the BC ERα status can be determined accurately as the reagent provides higher IS. Therefore, the A-score was higher than the MMAb 1D5. Ultimately, higher IS and A-score decrease the possibility of ERα status misinterpretation and, consequently, inappropriate BC treatment that would compromise the patient's quality of life and overall survival. We recommend the use of anti-ER RMAb SP1 due to the high probability that the BC ER status can be determined accurately as the reagent provides higher IS, therefore higher A-score, than the MMAb 1D5.}, } @article {pmid23011826, year = {2012}, author = {Pala, EE and Bayol, Ü and Cumurcu, S and Keskın, E}, title = {[Immunohistochemical characteristics of triple negative/basal-like breast cancer].}, journal = {Turk patoloji dergisi}, volume = {28}, number = {3}, pages = {238-244}, doi = {10.5146/tjpath.2012.01130}, pmid = {23011826}, issn = {1309-5730}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carrier Proteins/analysis/biosynthesis ; ErbB Receptors/analysis/biosynthesis ; Female ; Glycoproteins/analysis/biosynthesis ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Keratin-5/analysis/biosynthesis ; Keratin-6/analysis/biosynthesis ; Membrane Transport Proteins ; }, abstract = {OBJECTIVE: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.

MATERIAL AND METHOD: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytokeratine 5/6, p53, Ki67, GCDFP-15 expression profiles, HER2 and Chromosome 17 centromere gene status by fluorescence-in-situ-hybridization method.

RESULTS: Histological type was invasive ductal carcinoma in 90.2% of the tumors. p53, Ki67, GCDFP-15 mean positivity rates were 55.6%, 51.7%, and 3.2%, respectively. GCDFP-15 positivity was noted in 8 cases of which 6 were Cytokeratine 5/6 negative. The cut-off value for Cytokeratine 5/6 positivity was 5%. EGFR immunoreactivity was grouped into 0, 1+ as negative; 2+, 3+ as positive categories. Cytokeratine 5/6 was positive in 56,1%, EGFR was positive in 51.2% of the patients. The relation between Cytokeratine 5/6 and EGFR expression was statistically significant (p < 0.01). None of the cases showed HER2 amplification by fluorescence-in-situ-hybridization method.

CONCLUSION: GCDFP-15 alone is not a useful marker to detect the metastasis of basaloid type breast cancers. Cytokeratine 5/6 and EGFR expressions showed correlation so these markers are reliable to diagnose basaloid type tumors with a 5% cut-off value.}, } @article {pmid23002918, year = {2012}, author = {Suhrke, P and Mæhlen, J and Zahl, PH}, title = {Hormone therapy use and breast cancer incidence by histological subtypes in Sweden and Norway.}, journal = {The breast journal}, volume = {18}, number = {6}, pages = {549-556}, doi = {10.1111/tbj.12001}, pmid = {23002918}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/epidemiology ; Carcinoma, Lobular/epidemiology/pathology ; Female ; Hormone Replacement Therapy/*adverse effects/statistics & numerical data/trends ; Humans ; Mammography/statistics & numerical data ; Mass Screening ; Middle Aged ; Norway/epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {Mammography screening and postmenopausal hormone therapy (HT) both influence breast cancer incidence. While breast cancer incidence increased by around 50% during the introduction of screening, a smaller decline in incidence has been reported in several countries after 2002 when the sales of HT started to decline. Data suggest that HT increases the risk of the second most common type of breast cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal carcinoma (IDC). Breast cancer incidences stratified on histological subtypes were obtained from the national cancer registries. HT sales data from drug consumption statistics and information on the county-level introduction of mammography screening were combined, and breast cancer incidence trends were estimated using Poisson regression models, focusing on the period after 2002. From 2002 to 2007 the annual decrease in breast cancer incidence rates for women aged 50-69 was 1.5% (95% CI -2.3% to -0.7%) in Sweden and 0.8% (95% CI -2.8% to 1.2%) in the part of Norway not confounded by prevalence screening. Most of the decline was in the rates of ILC which dropped by 4.7% (95% CI -6.6% to -2.7%) and 7.0% (95% CI -12.8% to -0.9%) per year, respectively. The rates of IDC were stable in this period. Breast cancer incidence has declined in Sweden and Norway since 2002, but the reduction is moderate compared with the large increase that occurred during the introduction of mammography screening. Declining rates of ILC, but not of IDC, support the hypothesis that the drop in breast cancer incidence is associated with reduced HT use.}, } @article {pmid23002043, year = {2013}, author = {Vírseda, M and Salinas, J and Esteban, M and Méndez, S}, title = {Reliability of ambulatory urodynamics in patients with spinal cord injuries.}, journal = {Neurourology and urodynamics}, volume = {32}, number = {4}, pages = {387-392}, doi = {10.1002/nau.22303}, pmid = {23002043}, issn = {1520-6777}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Pressure ; Reproducibility of Results ; Sample Size ; Spinal Cord Injuries/*physiopathology ; Urinary Bladder/physiology/physiopathology ; Urinary Catheterization ; Urination ; Urodynamics/*physiology ; }, abstract = {OBJECTIVE: To determine the test-retest repeatability of the urodynamic parameters commonly utilized in ambulatory urodynamics (AM) for patients with neurogenic lower urinary tract dysfunction (NLUTD).

METHODS: A test-retest repeatability study was performed on 64 consecutive patients with stable spinal cord injuries who underwent two AM studies 24 hr apart.

RESULTS: The mean age was 43.2 years, with 47 males and 17 females. A significant intraclass correlation coefficient (ICC) was found between the two studies with respect to the functional bladder capacity (FBC; 0.74), the maximum detrusor pressure during the involuntary detrusor contraction (P(detmaxIDC); 0.84), and the post-void residual (PVR; 0.76). Of note, the ICC of the end filling detrusor pressure (P(detfill)) was not significant (0.25). The correlation with respect to the presence of involuntary detrusor contraction (IDC) was significant but low (κ = 0.40). Based on the logistic regression analysis, the variables that influenced the concordance with respect to the presence of the IDC were P(detmaxIDC) (directly) and P(detmax) (inversely). The variable that that influenced the concordance with respect to P(detmaxIDC) was PVR (directly). The variable that influenced the concordance with respect to PVR was the FBC (directly).

CONCLUSIONS: AM is reliable for the reproduction of the main urodynamic parameters investigated in patients with NLUTD, except for the end filling detrusor pressure, which was a non-reliable parameter. The concordance of AM can be improved primarily by taking into account the values of the maximum detrusor pressure during involuntary detrusor contraction (P(detmaxIDC)).}, } @article {pmid22997390, year = {2012}, author = {Zhu, Y and Zhang, S and Liu, P and Lu, H and Xu, Y and Yang, WT}, title = {Solitary intraductal papillomas of the breast: MRI features and differentiation from small invasive ductal carcinomas.}, journal = {AJR. American journal of roentgenology}, volume = {199}, number = {4}, pages = {936-942}, doi = {10.2214/AJR.12.8507}, pmid = {22997390}, issn = {1546-3141}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Contrast Media ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Papilloma, Intraductal/*diagnosis/pathology ; }, abstract = {OBJECTIVE: Intraductal papilloma of the breast can resemble invasive ductal carcinoma (IDC). The purpose of this study was to characterize MRI features of solitary intraductal papillomas and identify features that differentiate intraductal papillomas from small IDCs.

MATERIALS AND METHODS: Forty-four intraductal papillomas and 49 small (diameter≤2.0 cm) IDCs confirmed by histopathology were included. Analysis of MR findings included morphology, signal intensity preenhancement, time-signal intensity curve (TIC), enhancement degree, and evolution of enhancement pattern on dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging. The chi-square test and independent-samples Student t test were performed.

RESULTS: Of 44 intraductal papillomas, 27 (61.4%) were round or oval and 17 (38.6%) were irregular in shape, whereas 38 of 49 (77.6%) IDCs showed irregular or lobular shape (p<0.001). Smooth margins were seen in 43.2% (19/44) of the intraductal papillomas and 8.2% (4/49) of the IDCs. Most intraductal papillomas and IDCs showed slightly higher signal intensity on T2-weighted images. On DCE-MRI, 68.2% (30/44) of intraductal papillomas and 12.2% (6/49) of IDCs showed an early homogeneous or heterogeneous to delayed rimlike enhancement pattern (p=0.000). The difference in early-phase enhancement rates between intraductal papillomas (155.41%±19.15%) and IDCs (176.40%±35.61%) was significant (p=0.001). Differences in TIC and apparent diffusion coefficient values between the two groups were not significant.

CONCLUSION: A low early-phase enhancement rate and evolution of the DCE-MRI enhancement pattern from homogeneous or heterogeneous enhancement to rim enhancement is more likely to suggest intraductal papilloma than IDC.}, } @article {pmid22997389, year = {2012}, author = {Niell, B and Specht, M and Gerade, B and Rafferty, E}, title = {Is excisional biopsy required after a breast core biopsy yields lobular neoplasia?.}, journal = {AJR. American journal of roentgenology}, volume = {199}, number = {4}, pages = {929-935}, doi = {10.2214/AJR.11.8447}, pmid = {22997389}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Large-Core Needle ; Breast Neoplasms/pathology/*surgery ; Carcinoma in Situ/pathology/surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; Humans ; Middle Aged ; }, abstract = {OBJECTIVE: The management of lobular neoplasia (LN) on percutaneous core breast biopsies remains controversial. Published upgrade rates after surgical excision vary widely. This study aims to determine the frequency of malignancy following excision in patients with LN found on core biopsy.

SUBJECTS AND METHODS: Our study identified patients from December 2005 through December 2010 with LN as the highest-risk lesion on core biopsy. Patients with flat epithelial atypia on core biopsy were not excluded. Per institutional policy, excision was routinely recommended. An upgrade from the core biopsy of LN was defined as excisional biopsy pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), or invasive lobular carcinoma (ILC).

RESULTS: Between December 2005 and December 2010, 4472 percutaneous breast biopsies were performed, with 71 patients (1.5%) having LN as the highest-risk lesion on core biopsy. Sixty-seven patients (94%) underwent excision. The upgrade rate on excisional biopsy was 16% (11/67 patients), with the type of malignancy on excisional biopsy pathology as follows: DCIS, 36% (4/11); IDC, 18% (2/11); and ILC, 45% (5/11). All patients with pleomorphic lobular carcinoma in situ on core biopsy who proceeded to excision were upgraded to malignancy. After excluding patients with discordant results, patients with pleomorphic lobular carcinoma in situ, and patients with flat epithelial atypia on core biopsy, the upgrade rate of pure LN on excisional biopsy was 9%.

CONCLUSION: LN on core biopsy warrants excisional biopsy given the upgrade rate to malignancy.}, } @article {pmid22996916, year = {2013}, author = {Aho, M and Irshad, A and Ackerman, SJ and Lewis, M and Leddy, R and Pope, TL and Campbell, AS and Cluver, A and Wolf, BJ and Cunningham, JE}, title = {Correlation of sonographic features of invasive ductal mammary carcinoma with age, tumor grade, and hormone-receptor status.}, journal = {Journal of clinical ultrasound : JCU}, volume = {41}, number = {1}, pages = {10-17}, pmid = {22996916}, issn = {1097-0096}, support = {UL1 RR029882/RR/NCRR NIH HHS/United States ; UL1 TR000062/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/pathology ; Female ; Humans ; Middle Aged ; *Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: To determine whether presenting sonographic features of invasive ductal carcinomas (IDC) are associated with patient age, tumor histologic grade, and hormonal receptor status.

METHODS: Sonographic features of 101 consecutive cases of IDC seen at ultrasound were retrospectively assessed based on the BI-RADS criteria of posterior acoustic appearance, tumor margins, and echogenicity. Associations between sonographic features and tumor characteristics were statistically evaluated with attention to patient age.

RESULTS: IDC with shadowing compared with unchanged posterior acoustic appearance were significantly more likely to be of low histologic grade (Odds Ratio [OR] = 5.00; p < 0.05) and estrogen receptor (ER) -positive (OR = 10.00; p < 0.05). Conversely, posterior enhancement was associated with ER-negative status (OR = 4.45; p < 0.01), particularly among patients younger than 60 years of age (OR = 5.36, p < 0.05). Circumscribed tumors were more often high grade, particularly among older women (p < 0.01), and hormone receptor--negative regardless of age group. Among older women, tumors with mixed echogenicity tended to be high grade and progesterone receptor--negative (p values < 0.05). Noncircumscribed borders were observed for all tumors with posterior shadowing, and 97% of such tumors were also ER positive.

CONCLUSIONS: Sonographic features were significantly associated with tumor grade and hormone receptor status, with some differences based on patient age. Specifically, the presence of posterior shadowing was associated with lower histologic grade and ER-positive status, especially in older patients. In contrast, we found that posterior acoustic enhancement was more commonly associated with ER-negative status, especially in younger patients.}, } @article {pmid22996366, year = {2012}, author = {Son, CH and Shin, DY and Kim, SD and Park, HS and Jung, MH and Bae, JH and Kang, CD and Yang, K and Park, YS}, title = {Improvement of antitumor effect of intratumoral injection of immature dendritic cells into irradiated tumor by cyclophosphamide in mouse colon cancer model.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {35}, number = {8}, pages = {607-614}, doi = {10.1097/CJI.0b013e31826f79a6}, pmid = {22996366}, issn = {1537-4513}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*administration & dosage ; CD4 Antigens/metabolism ; Carcinoma/pathology/*therapy ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Colonic Neoplasms/pathology/*therapy ; Combined Modality Therapy ; Cyclophosphamide/*administration & dosage ; Dendritic Cells/transplantation ; Disease Models, Animal ; Humans ; Interferon-gamma/metabolism ; Interleukin-2 Receptor alpha Subunit/metabolism ; Lymphocyte Activation/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Radioimmunotherapy/*methods ; T-Lymphocyte Subsets/*drug effects/immunology ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {Recently, chemotherapy and radiotherapy are known to directly affect some immunosuppressive barriers within a tumor microenviroment. We used cyclophosphamide (CTX), which is known to enhance the immune response by suppressing CD4+CD25+ regulatory T cells (Treg cells) when used at a low dose, as a chemotherapeutic agent to provide a synergic effect in the irradiation and dendritic cells (DC) combination therapy. Some previous studies observed that a single-dose CTX treatment significantly reduced the number of Treg cells in 3-5 days, however, the reduced Treg cells increased rapidly after 5 days. To overcome the disadvantages of a single-dose CTX, we used 30 mg/kg dose of CTX, which was treated intraperitoneally to mice 3 days before every immature DC (iDC) injection (known as "metronomic schedule CTX"). Irradiation was applied at a dose of 10 Gy to the tumor on the right thigh by a linear accelerator. Then, iDC was intratumorally injected into the irradiated tumor site. Growth of a distant tumor on the right and left flank was suppressed by an injection of iDC into the irradiated tumor, and this effect was increased by the metronomic schedule CTX. Also, combinations treated with the metronomic schedule CTX and ionizing radiation (IR)/iDC, showed the longest survival time compared with other groups. This antitumor immune response of IR/iDC was improved by metronomic schedule CTX and this result was associated with decreasing the proportion of CD4+CD25+ Treg cells and increasing the number of tumor-specific interferon-γ-secreting T cells. Our results demonstrated that metronomic schedule CTX improves the antitumor effect of immunization with an injection of DC s into the irradiated tumor.}, } @article {pmid22989547, year = {2012}, author = {Kung, YH and Wu, TT and Lin, CS}, title = {Tumor seeding after diagnostic vitrectomy for choroidal metastasis in breast cancer.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {75}, number = {9}, pages = {483-486}, doi = {10.1016/j.jcma.2012.06.023}, pmid = {22989547}, issn = {1728-7731}, mesh = {Breast Neoplasms/*pathology ; Choroid Neoplasms/diagnosis/pathology/*secondary ; Female ; Humans ; Middle Aged ; *Neoplasm Seeding ; *Vitrectomy ; }, abstract = {Choroidal metastasis is the most common type of intraocular tumor in adults, and in females the most common primary site is the breast. We report a case of unilateral choroidal metastasis with exudative retinal detachment as the initial presentation of recurrent breast cancer, and subsequent ophthalmic metastasis following diagnostic vitrectomy. A 49-year-old woman with a 7-year-history of well-treated bilateral breast cancer had been suffering from blurred vision in the left eye for 1 week. Ocular examination was normal except for superotemporal retinal detachment in the left eye. Neither retinal break nor choroidal mass was seen. The patient received scleral buckling and pneumatic retinopexy without significant improvement. Fluorescein angiography revealed a suspected choroidal metastasis in the left eye, but ocular ultrasonography did not show a visible choroidal mass. Two consecutive diagnostic vitrectomies with cytology could not confirm malignancy. A systemic workup was also negative. Six months later, two tumor masses were noted over two of the sclerotomy wounds of the left eye. Pathology showed adenocarcinoma compatible with invasive ductal carcinoma of the breast. Ocular metastasis may present as infiltrative choroidal lesions with exudative retinal detachment without a visible mass. Invasive procedures, such as fine-needle aspiration biopsy and diagnostic vitrectomy, may risk tumor seeding.}, } @article {pmid22984615, year = {2012}, author = {van Balkom, ID and Bresnahan, M and Vuijk, PJ and Hubert, J and Susser, E and Hoek, HW}, title = {Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: Aruba.}, journal = {PloS one}, volume = {7}, number = {9}, pages = {e45090}, pmid = {22984615}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Age Factors ; Autistic Disorder/*epidemiology/ethnology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Indians, South American ; Logistic Models ; Male ; Maternal Age ; Middle Aged ; Netherlands/ethnology ; *Paternal Age ; Risk Assessment/methods/*statistics & numerical data ; Risk Factors ; Spain/ethnology ; West Indies/epidemiology ; }, abstract = {OBJECTIVE: The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.

DESIGN: A case-control study of Aruban-born children (1990-2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤ 29, 30-39, 40-49, ≥ 50 y). The analysis was made, using conditional logistic regression.

RESULTS: Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤ 29 y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.

CONCLUSION: This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.}, } @article {pmid22982673, year = {2012}, author = {Qian, XL and Li, YQ and Gu, F and Liu, FF and Li, WD and Zhang, XM and Fu, L}, title = {Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients.}, journal = {Biochemical and biophysical research communications}, volume = {427}, number = {1}, pages = {60-66}, doi = {10.1016/j.bbrc.2012.08.147}, pmid = {22982673}, issn = {1090-2104}, mesh = {Adult ; Aged ; Animals ; *Apoptosis ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*enzymology/*mortality/pathology ; Creatine Kinase, Mitochondrial Form/*biosynthesis ; Female ; Humans ; Mice ; Middle Aged ; Neoplasm Transplantation ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: Ubiquitous mitochondrial creatine kinase (uMtCK), a mitochondrial isoenzyme of creatine kinase (CK), is a central controller of cellular energy homeostasis. Overexpression of uMtCK has been reported to be associated with a poor prognosis for several tumors. The aim of this study was to assess its association with breast cancer (BCa) and to further investigate its underlying mechanisms.

METHOD: We first detected uMtCK expression by immunohistochemistry in human BCa tissues and assessed the association with the prognosis of patients. We then evaluated uMtCK expression in crowded and normal condition cultures of several human BCa cell lines. After two stable clones of the MDA-MB-231 cell line with high expression of uMtCK were established, cell growth, apoptosis and mitochondrial apoptotic pathway protein expression were measured in these clones. Finally, tumorigenicity of the above cells was assessed using nude mice to explore the relationship between uMtCK expression and tumor progression.

RESULTS: uMtCK expression was detected in 85.5% (47 of 55) of the invasive ductal carcinomas of breast tissue, not otherwise specified (IDC-NOS). Expression in BCa tissue was significantly associated with reduced progression-free survival (PFS; P=0.019) and overall survival (OS; P=0.022) of the patients. Up-regulation of uMtCK expression was identified in crowded BCa cells in culture, and the number of apoptotic cells was significantly decreased in uMtCK transfected MDA-MB-231 cell clones (P<0.01). Stabilization of the mitochondrial membrane potential (ΔΨm) and down regulation of cytochrome c (cyt c) and activated caspase 9, two components of mitochondrial apoptotic pathway proteins, were also identified in the same clones when cells were crowded in culture. In vivo studies revealed that the transfected tumor cells with uMtCK overexpression induced faster tumor growth in nude mice, along with accelerated animal body weight loss and a significantly lower tumor apoptotic index (AI) (P<0.001).

CONCLUSION: The results indicated that uMtCK expression is associated with a poor prognosis in BCa and might serve as a tumor marker. In vivo and In vitro evidence suggests that uMtCK overexpression promotes tumor growth by inhibiting apoptosis of tumor cells through stabilizing ΔΨm and down regulating mitochondrial apoptotic pathway proteins. Exploration of therapeutic agents targeting the expression of uMtCK may have practical value for BCa patients.}, } @article {pmid22976804, year = {2012}, author = {Li, S and Yang, C and Zhai, L and Zhang, W and Yu, J and Gu, F and Lang, R and Fan, Y and Gong, M and Zhang, X and Fu, L}, title = {Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast.}, journal = {Breast cancer research and treatment}, volume = {136}, number = {1}, pages = {77-87}, doi = {10.1007/s10549-012-2166-6}, pmid = {22976804}, issn = {1573-7217}, mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Carcinoma, Papillary/genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphatic Metastasis ; *MicroRNAs/genetics/isolation & purification ; Neoplasm Invasiveness/genetics ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.}, } @article {pmid22975899, year = {2012}, author = {Rodríguez Pérez, A and López Carrizosa, MC and Samper Ots, PM and Pérez-Regadera Gómez, JF and Zapatero Ortuño, J and Sáez Garrido, Jde D and Martín de Miguel, MJ}, title = {Conservative surgery, external radiotherapy, and HDR brachytherapy in a single fraction of 7 Gy in early breast cancer: long-term toxicity and esthetic assessment.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {14}, number = {12}, pages = {953-960}, pmid = {22975899}, issn = {1699-3055}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brachytherapy/adverse effects ; Breast/pathology/*radiation effects/*surgery ; Breast Neoplasms/pathology/*radiotherapy/*surgery ; Dose Fractionation, Radiation ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Prospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: The essential issue in conservative treatment is the quality in breast preservation. When risk factors for local relapse exist, a tumour bed boost is required, but the boost choice remains controversial. Prospectively, we studied long-term toxicity, cosmetic outcome and prognostic factors.

MATERIALS AND METHODS: After conservative treatment, 115 patients received a single dose of 7 Gy HDR-brachytherapy (HDR-BT) boost between June 1996 and December 2005. Late toxicity was assessed using the LENT-SOMA scale. For esthetic assessment, a subjective scale was used for patients and a modified Fehlauer scale for physicians. Mean age was 56.6 years. Invasive ductal carcinoma (78 %) and lumpectomy (60 %) were predominantly reported. 48 % received chemotherapy (CT).

RESULTS: Regarding toxicity, 39 % of patients reported breast pain, 75 % fibrosis, 56 % telangiectasias, 19 % lymphoedema, and 51 % retraction/atrophy. Concerning management, 22 % of patients with pain and 45 % with lymphoedema were treated. The esthetic result was found satisfactory by 96 % of the patients and 85 % of the physicians. Fibrosis was influenced by CT and a larger irradiated volume and telangiectasias by a greater implant volume.

CONCLUSIONS: HDR-BT boost shows good cosmetic effects with acceptable toxicity. Patients overestimate the esthetic outcome. LENT/SOMA is useful to assess chronic toxicity.}, } @article {pmid22968776, year = {2012}, author = {Boggis, D}, title = {Effectiveness of a developmental curricular design to graduate culturally competent health practitioners.}, journal = {Journal of allied health}, volume = {41}, number = {3}, pages = {140-146}, pmid = {22968776}, issn = {1945-404X}, mesh = {Adult ; Cultural Competency/*education ; *Curriculum ; Education, Graduate/*organization & administration ; Female ; Humans ; Male ; Occupational Therapy/*education ; }, abstract = {With the goal to facilitate cultural competency development of students enrolled in graduate-level health professional education, this study examined the effectiveness of a curricular program guided by the Intercultural Developmental Continuum (IDC) as measured by the Intercultural Developmental Inventory (IDI). The IDI was administered to 17 occupational therapy (OT) students and a control group of 25 non-OT health professional students upon matriculation into their respective programs of graduate study and again upon completion of 3 years of study. OT students participated in a cultural curricular design guided by the IDC, while the control group participated in cultural study not guided by the IDC. Though OT students did not show a significant change in overall developmental orientation mean scores from pre-test to post-test (t = 0.847, p = 0.41), the results indicate that the designed intercultural curriculum increased intercultural competence among those OT students who began their program with the monocultural mindset of polarization (an "us vs. them" evaluative viewpoint) and moved to the interculturally transitional mindset of minimization (recognizing cultural commonalities and elimination of the "us vs. them" mindset). The control group showed a significant decrease in developmental orientation mean scores at post-test (t = 6.1, p < 0.001). No significant group or group by baseline interaction effects were found when comparing overall post-developmental scores adjusting for baseline (F = 2.4, p = 0.131). The curriculum design as guided by the IDC, though it did not significantly increase overall cultural competency of OT students, appears to have mitigated a decrease in competence. Results suggest that the cultural challenges that students face appear to be considerable and, without targeted, integrated intercultural preparation, can overwhelm new health professionals' intercultural capability.}, } @article {pmid22961104, year = {2012}, author = {Uzoaru, I and Morgan, BR and Liu, ZG and Bellafiore, FJ and Gaudier, FS and Lo, JV and Pakzad, K}, title = {Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {461}, number = {4}, pages = {419-423}, pmid = {22961104}, issn = {1432-2307}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle ; Breast/*pathology/*surgery ; Breast Neoplasms/diagnosis/*epidemiology/*surgery ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/surgery ; Carcinoma, Lobular/diagnosis/epidemiology/surgery ; Epithelial Cells/*pathology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Incidence ; Longitudinal Studies ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Retrospective Studies ; Risk Factors ; }, abstract = {Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. There were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had microcalcifications on mammography with 65.5 % (95/145) of patients undergoing subsequent excisional biopsies with the following findings: benign 20 % (19/95), ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 % (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43), DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ + invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95) for the pure FEA group. This difference is statistically significant (p = 0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow-up in the unexcised pure FEA did not show any malignancies. These findings suggest that pure FEA has a very low association with carcinoma, and these patients may benefit from close clinical and mammographic follow-up while the combined pure FEA and ADH cases may be re-excised.}, } @article {pmid22961065, year = {2012}, author = {Lips, EH and Mukhtar, RA and Yau, C and de Ronde, JJ and Livasy, C and Carey, LA and Loo, CE and Vrancken-Peeters, MJ and Sonke, GS and Berry, DA and Van't Veer, LJ and Esserman, LJ and Wesseling, J and Rodenhuis, S and Shelley Hwang, E and , }, title = {Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {136}, number = {1}, pages = {35-43}, pmid = {22961065}, issn = {1573-7217}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Breast Neoplasms/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Lobular/drug therapy/metabolism/pathology/surgery ; Clinical Trials as Topic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mastectomy, Segmental ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Receptor, ErbB-2/genetics/metabolism ; Treatment Outcome ; }, abstract = {Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.}, } @article {pmid22957844, year = {2012}, author = {Zhu, J and Li, X and Kong, X and Moran, MS and Su, P and Haffty, BG and Yang, Q}, title = {Testin is a tumor suppressor and prognostic marker in breast cancer.}, journal = {Cancer science}, volume = {103}, number = {12}, pages = {2092-2101}, pmid = {22957844}, issn = {1349-7006}, mesh = {Animals ; Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Cell Proliferation ; Cytoskeletal Proteins/genetics/*metabolism ; Disease-Free Survival ; Female ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; NIH 3T3 Cells ; Prognosis ; RNA-Binding Proteins ; Xenograft Model Antitumor Assays ; }, abstract = {The testin (TES) gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. In the present study, we aimed to investigate the candidate tumor suppressor function of TES and explore its correlations to clinicopathologic features and prognosis in breast cancer. In clinical samples, we showed that the expression of TES decreased gradually from normal through ductal hyperplasia without atypia, atypical ductal hyperplasia, and ductal carcinoma in situ, to invasive ductal carcinoma. To explore the possible tumor suppressing function of TES, the expression of TES in breast cancer cells was manipulated by ectopic expression or by RNAi. We revealed that ectopic TES expression significantly inhibited cell proliferation, invasive ability, and angiogenesis, whereas knockdown of TES by RNAi enhanced cell proliferation, invasive ability, and angiogenesis. In an animal model, TES markedly inhibited breast cancer cell xenograft formation in athymic nude mice and reduced breast cancer cell metastasis to lung. Moreover, we revealed that TES inhibited the invasion and angiogenesis of breast cancer partially through miR-29b-mediated MMP-2 inhibition. Using the tissue microarray of breast cancer from Yale University, we found that lower TES expression was an independent prognostic factor for shorter overall survival and disease-free survival with univariate and multivariate analyses. Taken together, these data suggest that TES, as a valuable marker of breast cancer prognosis, plays an important role in the development and progression of breast cancer. TES may be an effective novel target in breast cancer prevention and treatment.}, } @article {pmid22954666, year = {2013}, author = {van de Water, W and Fontein, DB and van Nes, JG and Bartlett, JM and Hille, ET and Putter, H and Robson, T and Liefers, GJ and Roumen, RM and Seynaeve, C and Dirix, LY and Paridaens, R and Kranenbarg, EM and Nortier, JW and van de Velde, CJ}, title = {Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {49}, number = {2}, pages = {297-304}, doi = {10.1016/j.ejca.2012.07.026}, pmid = {22954666}, issn = {1879-0852}, mesh = {Aged ; Androstadienes/administration & dosage/*therapeutic use ; Antineoplastic Agents, Hormonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Carcinoma, Lobular/*drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Postmenopause ; Receptors, Estrogen/*biosynthesis ; Tamoxifen/administration & dosage ; }, abstract = {BACKGROUND: Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated.

METHODS: Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse.

FINDINGS: Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003).

INTERPRETATION: Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression.}, } @article {pmid22949099, year = {2013}, author = {Bonkhoff, H and Wheeler, TM and van der Kwast, TH and Magi-Galluzzi, C and Montironi, R and Cohen, RJ}, title = {Intraductal carcinoma of the prostate: precursor or aggressive phenotype of prostate cancer?.}, journal = {The Prostate}, volume = {73}, number = {4}, pages = {442-448}, doi = {10.1002/pros.22579}, pmid = {22949099}, issn = {1097-0045}, mesh = {Animals ; Carcinoma, Ductal/*genetics/*pathology ; Humans ; Male ; Neoplasm Invasiveness/*genetics/*pathology ; *Phenotype ; Prostatic Neoplasms/*genetics/*pathology ; }, abstract = {BACKGROUND: Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high grade prostatic intraepithelial neoplasia (HGPIN).

METHODS: Recent data obtained from histological, molecular, and clinical studies were reviewed to demonstrate that IDC-P significantly differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and therapy of prostate cancer (PCa).

RESULTS: HGPIN is the only accepted precursor of PCa. Its diagnosis in prostate biopsies has no prognostic implications, and does not dictate therapeutic decisions. By contrast, IDC-P correlates with a worse pathological and clinical outcome. IDC-P differs from HGPIN by distinct histological and molecular features. Recent clinical studies report that IDC-P is associated with neoadjuvant androgen deprivation therapy (ADT) and, chemotherapy (CT) failure as well as early disease recurrence after external beam radiation. Finally, IDC-P is associated with TMPRSS2-ERG gene fusion, which was reported to be regulated by estrogens and their receptors.

CONCLUSIONS: IDC-P is an aggressive phenotype of prostate cancer and predicts poor response to ADT, CT, and external beam radiation. IDC-P should be separated from HGPIN and should be reported in prostate biopsies and prostatectomy specimens.}, } @article {pmid22940831, year = {2012}, author = {Hori, M and Onaya, H and Takahashi, M and Hiraoka, N and Mutoh, M and Kosuge, T and Nakagama, H}, title = {Invasive ductal carcinoma developing in pancreas with severe Fatty infiltration.}, journal = {Pancreas}, volume = {41}, number = {7}, pages = {1137-1139}, doi = {10.1097/MPA.0b013e318252ea08}, pmid = {22940831}, issn = {1536-4828}, mesh = {Adipose Tissue/*pathology ; Aged ; Carcinoma, Pancreatic Ductal/*pathology/surgery ; Humans ; Male ; Pancreatic Neoplasms/*pathology/surgery ; }, } @article {pmid22934236, year = {2012}, author = {Buckley, JM and Coopey, SB and Sharko, J and Polubriaginof, F and Drohan, B and Belli, AK and Kim, EM and Garber, JE and Smith, BL and Gadd, MA and Specht, MC and Roche, CA and Gudewicz, TM and Hughes, KS}, title = {The feasibility of using natural language processing to extract clinical information from breast pathology reports.}, journal = {Journal of pathology informatics}, volume = {3}, number = {}, pages = {23}, pmid = {22934236}, issn = {2153-3539}, abstract = {OBJECTIVE: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports. APPROACH AND PROCEDURE: Breast pathology reports from three institutions were analyzed using natural language processing software (Clearforest, Waltham, MA) to extract information on a variety of pathologic diagnoses of interest. Data tables were created from the extracted information according to date of surgery, side of surgery, and medical record number. The variety of ways in which each diagnosis could be represented was recorded, as a means of demonstrating the complexity of machine interpretation of free text.

RESULTS: There was widespread variation in how pathologists reported common pathologic diagnoses. We report, for example, 124 ways of saying invasive ductal carcinoma and 95 ways of saying invasive lobular carcinoma. There were >4000 ways of saying invasive ductal carcinoma was not present. Natural language processor sensitivity and specificity were 99.1% and 96.5% when compared to expert human coders.

CONCLUSION: We have demonstrated how a large body of free text medical information such as seen in breast pathology reports, can be converted to a machine readable format using natural language processing, and described the inherent complexities of the task.}, } @article {pmid22932921, year = {2013}, author = {Liu, ZY and Liu, N and Wang, YH and Yang, CC and Zhang, J and Lv, SH and Niu, Y}, title = {Clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast: a large case study.}, journal = {Journal of cancer research and clinical oncology}, volume = {139}, number = {1}, pages = {77-84}, pmid = {22932921}, issn = {1432-1335}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/mortality/*pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/therapy ; Carcinoma, Lobular/pathology/therapy ; Carcinoma, Papillary/metabolism/mortality/*pathology/*therapy ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Immunophenotyping ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Proportional Hazards Models ; Retrospective Studies ; }, abstract = {PURPOSE: Although patients with invasive papillary carcinoma (IPC) often have favorable prognoses, it remains unclear whether this special type of breast cancer represents a distinct morphological entity with its own biological features and clinical behavior distinct from those of invasive ductal carcinoma (IDC) and whether its four molecular subtypes are associated with different prognoses.

METHODS: The study is a retrospective analysis of a large patient cohort from a single institution. 284 IPC samples were collected from January 2000 to May 2011. 300 IDC cases were selected randomly from 13,428 cases of IDC during the same periods. We assessed the clinicopathologic characteristics, molecular features, and prognostic value of IPC (n = 284) and compared them to those of IDC (n = 300). Clinicopathologic features and survival status of the four subtypes of IPC were also evaluated.

RESULTS: IPC differed from IDC with respect to age upon diagnosis, tumor grade, lymph node status, and menopausal status (P < 0.05). IPC was associated with a better 5-year overall survival rate (OS) (92.77 vs. 87.95 %) and disease-free survival rate (DFS) (87.95 vs. 80.72 %) than IDC. Tumors of the luminal A subtype had a better 5-year OS (97.78 %) and DFS (95.56 %) than other subtypes.

CONCLUSIONS: The biologic behavior of IPC is more favorable to patient outcome than that of IDC. The chance of pure IPC causing death without an intervening event of a different histologic type is exceptionally low. Luminal A subtypes have better outcomes when compared to the other subtypes.}, } @article {pmid22932738, year = {2013}, author = {Sztrókay, A and Herzen, J and Auweter, SD and Liebhardt, S and Mayr, D and Willner, M and Hahn, D and Zanette, I and Weitkamp, T and Hellerhoff, K and Pfeiffer, F and Reiser, MF and Bamberg, F}, title = {Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up.}, journal = {European radiology}, volume = {23}, number = {2}, pages = {381-387}, pmid = {22932738}, issn = {1432-1084}, mesh = {Aged ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/pathology/surgery ; Contrast Media ; Diagnosis, Differential ; Early Detection of Cancer/methods ; Female ; Humans ; Immunohistochemistry ; Mammography/methods ; Mastectomy/methods ; Radiographic Image Enhancement/methods ; *Radiographic Image Interpretation, Computer-Assisted ; Specimen Handling ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVE: Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS).

METHODS: Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion.

RESULTS: Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS.

CONCLUSIONS: Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS.}, } @article {pmid22931216, year = {2012}, author = {Yoshikawa, K and Mitsunaga, S and Kinoshita, T and Konishi, M and Takahashi, S and Gotohda, N and Kato, Y and Aizawa, M and Ochiai, A}, title = {Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head.}, journal = {Cancer science}, volume = {103}, number = {11}, pages = {2012-2020}, pmid = {22931216}, issn = {1349-7006}, mesh = {Adult ; Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry/methods ; Macrophages/metabolism/*pathology ; Male ; Middle Aged ; Pancreatic Neoplasms/metabolism/*pathology ; Pancreatitis, Chronic/pathology ; Scavenger Receptors, Class A/metabolism ; }, abstract = {Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor-associated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC.}, } @article {pmid22929011, year = {2012}, author = {To, SQ and Takagi, K and Miki, Y and Suzuki, K and Abe, E and Yang, Y and Sasano, H and Simpson, ER and Knower, KC and Clyne, CD}, title = {Epigenetic mechanisms regulate the prostaglandin E receptor 2 in breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {132}, number = {3-5}, pages = {331-338}, doi = {10.1016/j.jsbmb.2012.07.007}, pmid = {22929011}, issn = {1879-1220}, mesh = {Adipose Tissue/cytology ; Azacitidine/analogs & derivatives/pharmacology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line, Tumor ; CpG Islands ; DNA Methylation ; Decitabine ; *Epigenesis, Genetic ; Female ; Fibroblasts/metabolism ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase Inhibitors/pharmacology ; Histones/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Promoter Regions, Genetic ; Receptors, Prostaglandin E, EP2 Subtype/*genetics/metabolism ; Reference Values ; Stromal Cells/metabolism ; }, abstract = {The increase in local oestrogen production seen in oestrogen receptor positive (ER+) breast cancers is driven by increased activity of the aromatase enzyme. CYP19A1, the encoding gene for aromatase, is often overexpressed in the oestrogen-producing cells of the breast adipose fibroblasts (BAFs) surrounding an ER+ tumour, and the molecular processes underlying this upregulation is important in the development of breast-specific aromatase inhibitors for breast cancer therapy. Prostaglandin E2 (PGE2), a factor secreted by tumours, is known to stimulate CYP19A1 expression in human BAFs. The hormonal regulation of this process has been examined; however, what is less well understood is the emerging role of epigenetic mechanisms and how they modulate PGE2 signalling. This present study characterises the epigenetic processes underlying expression of the prostanoid receptor EP2 in the context of ER+ breast cancer. Sodium bisulphite sequencing of CpG methylation within the promoter region of EP2 revealed that an inverse correlation existed between methylation levels and relative EP2 expression in breast cancer cell lines MDA-MB-231, MCF7 and MCF10A but not in HS578t and T47D. Inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5aza) and histone deacetylation with Trichostatin A (TSA) resulted in upregulation of EP2 mRNA in all cell lines with varying influences of each epigenetic process observed. Expression of EP2 was detected in human BAFs despite a natively methylated promoter, and this expression was further increased upon 5aza treatment. An examination of 3 triple negative, 3 ductal carcinoma in situ and 3 invasive ductal carcinoma samples revealed that there was no change in EP2 promoter methylation status between normal and cancer associated stroma, despite observed differences in relative mRNA levels. Although EP2 methylation status is inversely correlated to expression levels in established breast cancer cell lines, we could not identify that such a correlation existed in tumour-associated stroma cells.}, } @article {pmid22926081, year = {2013}, author = {Bideault, G and Herault, R and Seifert, L}, title = {Data modelling reveals inter-individual variability of front crawl swimming.}, journal = {Journal of science and medicine in sport}, volume = {16}, number = {3}, pages = {281-285}, doi = {10.1016/j.jsams.2012.08.001}, pmid = {22926081}, issn = {1878-1861}, mesh = {Adolescent ; Cluster Analysis ; Female ; Humans ; Male ; Models, Biological ; Swimming/*physiology ; Young Adult ; }, abstract = {OBJECTIVES: In accordance with dynamical systems theory, which assumes that motor behaviour emerges from interacting constraints (task, organismic, environmental), this study explored the functional role of inter-individual variability in inter-limb coordination.

DESIGN: 63 front crawl swimmers with a range of characteristics (gender, performance level, specialty) performed seven intermittent graded speed bouts of 25m in front crawl.

METHODS: Each bout was video-taped with a side-view camera from which speed, stroke rate, stroke length and index of arm coordination (IdC) were analysed for three cycles. Cluster analysis was used to classify the swimmers through speed and IdC values.

RESULTS: Cluster analysis and validation showed four profiles of IdC management expressing the swimmers' characteristics as cluster 1: mainly national distance male swimmers, cluster 2: mainly international male sprinters, cluster 3: distinguished by female characteristics, and cluster 4: swimmers with the lowest level of performance.

CONCLUSIONS: These profiles generated different IdC-speed regression models, which (i) showed how the swimmers adapted their motor behaviour to overcome task constraints and (ii) supported the key idea that there is not a single ideal expert model to be imitated, but rather adapted behaviour emerging from individually encountered constraints.}, } @article {pmid22925754, year = {2012}, author = {Armağan, H and Tüzün, E and Içöz, S and Birişik, O and Ulusoy, C and Demir, G and Altıntaş, A and Akman-Demir, G}, title = {Long extensive transverse myelitis associated with aquaporin-4 antibody and breast cancer: favorable response to cancer treatment.}, journal = {The journal of spinal cord medicine}, volume = {35}, number = {4}, pages = {267-269}, pmid = {22925754}, issn = {1079-0268}, mesh = {Antineoplastic Agents/therapeutic use ; Aquaporin 4/*immunology ; Autoantibodies/blood/immunology ; Autoantigens/immunology ; Breast Neoplasms/*complications/immunology/therapy ; Carcinoma, Ductal, Breast/*complications/immunology/therapy ; Combined Modality Therapy ; Female ; Humans ; Mastectomy ; Middle Aged ; Myelitis, Transverse/*complications/immunology ; Paraneoplastic Syndromes/*etiology/immunology ; }, abstract = {CONTEXT: Long extensive transverse myelitis (LETM) seldom develops in patients with breast cancer who are aquaporin-4 antibody (Aqp-4 Ab)-positive. Whether this association is coincidental is not well understood.

FINDINGS: A 62-year-old woman presented with treatment-resistant LETM and Aqp-4 Ab. Two months later, a stage 3 invasive ductal carcinoma was detected in her right breast. Following tumor resection and chemotherapy, her neurologic symptoms and magnetic resonance imaging findings significantly improved and serum Aqp-4 Ab disappeared. The breast tumor samples of this patient and neurologically normal patients showed inflammatory infiltrates and Aqp-4 expressing cells.

CONCLUSION/CLINICAL RELEVANCE: The temporal association between tumor treatment, amelioration of clinical findings, and seroreversion suggest that coexistence of cancer and LETM is not coincidental. Cancer screening should be considered at least in treatment-resistant LETM cases.}, } @article {pmid22925694, year = {2012}, author = {Marzese, DM and Hoon, DS and Chong, KK and Gago, FE and Orozco, JI and Tello, OM and Vargas-Roig, LM and Roqué, M}, title = {DNA methylation index and methylation profile of invasive ductal breast tumors.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {14}, number = {6}, pages = {613-622}, doi = {10.1016/j.jmoldx.2012.07.001}, pmid = {22925694}, issn = {1943-7811}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/pathology ; Cluster Analysis ; *CpG Islands ; *DNA Methylation ; DNA-Binding Proteins/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Nuclear Proteins/genetics ; Prognosis ; Receptors, Retinoic Acid/genetics ; Tumor Protein p73 ; Tumor Suppressor Proteins/genetics ; WT1 Proteins/genetics ; }, abstract = {Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management.}, } @article {pmid22925655, year = {2012}, author = {Guo, Y and Xu, X and Liu, Z and Zhang, T and Zhang, X and Wang, L and Wang, M and Liu, Y and Lu, Y and Liu, Y and Quan, C}, title = {Apoptosis signal-regulating kinase 1 is associated with the effect of claudin-6 in breast cancer.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {111}, pmid = {22925655}, issn = {1746-1596}, mesh = {Adult ; Aged ; Apoptosis ; Blotting, Western ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Line, Tumor ; Claudins/genetics/*metabolism ; Enzyme Activation ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; MAP Kinase Kinase Kinase 5/genetics/*metabolism ; MCF-7 Cells ; Middle Aged ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Previous studies have demonstrated that claudin-6 functions as a cancer suppressor in human MCF-7 breast cancer cells. The growth inhibitory effect could be attributed to inhibition of cell proliferation and induction of apoptosis. The purpose of the current study was to examine the involvement of apoptosis signal-regulating kinase 1 (ASK1) in the anticancer effect of claudin-6.

METHODS: Immunohistochemical analysis was performed to evaluate the ASK1 protein expression and the correlation between ASK1, claudin-6 and clinicopathological features in 85 samples of breast invasive ductal carcinomas (IDC). Western blotting and RT-PCR was carried out to examine the expression of ASK1 and claudin-6 in MCF-7 cell clones transfected with claudin-6.

RESULTS: Immunohistochemical analysis showed that ASK1 expression was significantly related with that of claudin-6 in breast invasive ductal carcinomas (P < 0.05). In addition, a positive correlation between ASK1 and C-erb B 2 protein expression was identified (P < 0.05). Western blotting and RT-PCR consistently revealed that the level of ASK1 protein and mRNA was upregulated in MCF-7 cell clones transfected with claudin-6.

CONCLUSIONS: Our data suggests, for the first time, that the ASK1 signal may play a positive role in the inhibitory effect of claudin-6 in breast cancer.

VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1200314318763661.}, } @article {pmid22920283, year = {2012}, author = {Serce, N and Gnatzy, A and Steiner, S and Lorenzen, H and Kirfel, J and Buettner, R}, title = {Elevated expression of LSD1 (Lysine-specific demethylase 1) during tumour progression from pre-invasive to invasive ductal carcinoma of the breast.}, journal = {BMC clinical pathology}, volume = {12}, number = {}, pages = {13}, pmid = {22920283}, issn = {1472-6890}, abstract = {BACKGROUND: Lysine-specific demethylase1 (LSD1) is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS) in comparison to invasive ductal breast cancer (IDC).

METHODS: Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27), intermediate grade DCIS (n = 30), high grade DCIS (n = 31) and in invasive ductal breast cancer (n = 32). SPSS version 18.0 was used for statistical analysis.

RESULTS: LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma.

CONCLUSIONS: LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.}, } @article {pmid22915433, year = {2012}, author = {Blaichman, J and Marcus, JC and Alsaadi, T and El-Khoury, M and Meterissian, S and Mesurolle, B}, title = {Sonographic appearance of invasive ductal carcinoma of the breast according to histologic grade.}, journal = {AJR. American journal of roentgenology}, volume = {199}, number = {3}, pages = {W402-8}, doi = {10.2214/AJR.11.7374}, pmid = {22915433}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; Middle Aged ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: The purpose of this study was to compare the efficacy of the sonographic features in the BI-RADS lexicon for predicting malignancy grade of invasive ductal breast carcinoma in women assigned a BI-RADS category of 4 or 5.

MATERIALS AND METHODS: Two radiologists retrospectively evaluated 299 consecutive cases of grades 1-3 invasive ductal breast carcinoma presenting as a mass in consensus by using the BI-RADS sonographic lexicon. Histologic grade was established on surgical specimens. Effect sizes were calculated via the Goodman and Kruskal tau, an asymmetric measure of strength of nominal association, and results were interpreted in terms of proportional reduction in error.

RESULTS: Thirty-eight lesions (13%) were grade 1, 153 (51%) were grade 2, and 108 (36%) were grade 3, with the majority of all masses showing an irregular shape (84%) and hypoechoic echotexture (82%). Of the sonographic features examined, malignancy grade was best predicted by posterior acoustics (τ = 0.13, p < 0.001), lesion boundary (τ = 0.05, p < 0.001), and margin (τ = 0.04, p = 0.001). Among grade 3 lesions, there were significantly more lesions with posterior enhancement (53 vs 27.6; adjusted standardized residuals (z(res)) = 7; p < 0.001), abrupt interfaces (68 vs 51.2; z(res) = 4; p < 0.001), and microlobulated margins (12 vs 5.8; z(res) = 3; p = 0.001) than would be expected.

CONCLUSION: Malignancy grade was slightly to moderately predicted by margin, lesion boundary, and acoustic sonographic features. In particular, grade 3 invasive ductal breast carcinomas were more likely than expected to display microlobulated margins, abrupt interfaces, and posterior enhancement.}, } @article {pmid22914783, year = {2012}, author = {Yuan, SS and Hou, MF and Hsieh, YC and Huang, CY and Lee, YC and Chen, YJ and Lo, S}, title = {Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer.}, journal = {Journal of the National Cancer Institute}, volume = {104}, number = {19}, pages = {1485-1502}, doi = {10.1093/jnci/djs355}, pmid = {22914783}, issn = {1460-2105}, mesh = {Animals ; Apoptosis ; Breast Neoplasms/genetics/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/*pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; *Cell Proliferation ; Cell Survival ; Colorimetry ; *DNA Repair ; DNA-Binding Proteins/genetics/*metabolism ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunoblotting ; Immunohistochemistry ; Kaplan-Meier Estimate ; MRE11 Homologue Protein ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Tissue Array Analysis ; Transplantation, Heterologous ; Tumor Stem Cell Assay ; Up-Regulation ; }, abstract = {BACKGROUND: Previous studies have shown that altered forms of MRE11, a protein known to play a vital role in DNA double-strand break repair, DNA replication, and telomere maintenance are associated with cancer outcomes. We investigated the role of MRE11 in breast cancer in both clinical and in vitro settings.

METHODS: We examined MRE11 expression in tumor tissues from invasive ductal carcinoma breast cancer patients (n = 254) by immunohistochemistry, and associations with clinicopathological characteristics and overall survival were assessed using Cox proportional hazards regression models and Kaplan-Meier survival curves. Effect of MRE11 overexpression and knockdown on cell proliferation, invasion, and radioresistance was assessed in vitro using breast cancer cell lines (MCF-7 and MDA-MB-231). We also investigated the mechanisms involved. Effect of MRE11 overexpression on tumor growth was assessed in an orthotopic xenograft model (n = 8 mice per group). All statistical tests were two-sided.

RESULTS: Of the 254 tissue samples, 69.3% and 30.7% showed high and low MRE11 expression, respectively. High MRE11 expression was statistically significantly associated with malignant cancer behavior compared with low MRE11 expression (eg, stages III and IV vs stage I, P = .004; poor overall survival, P = .005). MRE11 overexpression in breast cancer cell lines promoted cell proliferation through STAT3, cell cycle entry, invasion and migration, and radioresistance via enhanced DNA repair activity and also inhibited apoptosis; knockdown of MRE11 had the opposite effect. In xenograft tumor-bearing mice (n = 8 per group), increased tumor growth was observed in the MRE11-overexpressing group compared with the control group (tumor volume at week 8, control vs MRE11-overexpressing tumor originating from MCF-7 cells, mean = 280.4 mm(3), 95% confidence interval [CI] = 62.4 to 498.4 mm(3) vs mean = 631.0 mm(3), 95% CI = 296.9 to 965.0 mm(3), P = .043).

CONCLUSION: High MRE11 expression was associated with a more malignant behavior in breast cancer. MRE11 may be a novel oncoprotein and may therefore serve as a new therapeutic intervention against breast cancer.}, } @article {pmid22907853, year = {2012}, author = {Zafar, A and Neary, P and O'Donoghue, G and Fiuza-Castinieria, C}, title = {A breast surgeon's paranoia pays off: the importance of keen clinical acumen in a case of postradiotherapy breast angiosarcoma.}, journal = {BMJ case reports}, volume = {2012}, number = {}, pages = {}, pmid = {22907853}, issn = {1757-790X}, mesh = {Aged ; Breast Neoplasms/*diagnosis/etiology/surgery ; Carcinoma, Ductal, Breast/*therapy ; Female ; Hemangiosarcoma/*diagnosis/etiology/surgery ; Humans ; Magnetic Resonance Imaging ; Neoplasms, Radiation-Induced/*diagnosis/etiology/surgery ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {A 72-year-old woman underwent left wide local excision and an axillary node sampling in 2005 for a T2, N0, M0 invasive ductal carcinoma followed by adjuvant chemotherapy, radiotherapy and hormonal therapy. In 2011, she developed spontaneous blue breast discolouration. Initial examination revealed global breast firmness, skin thickening and ecchymosis. Despite no evidence of recurrent disease, the patient was scheduled for fortnightly review. This review demonstrated marked worsening discolouration and new nipple areolar complex blood-filled blisters. Despite concurrent antiplatelet therapy as a possible cause, the breast clinician's clinical concern of angiosarcoma led to a skin punch biopsy, revealing only non-specific lymphocytic infiltrate. Interval mammographic assessment demonstrated non-specific architectural distortion. Regardless of these benign findings, a breast MRI was performed demonstrating possible breast angiosarcoma. Ultrasound-guided biopsy demonstrated low-grade breast angiosarcoma. The patient underwent completion mastectomy, for a 150 mm high-grade postradiotherapy angiosarcoma. Annual clinical review and contralateral mammography is planned.}, } @article {pmid22907775, year = {2013}, author = {Matsukawa, Y and Hattori, R and Sassa, N and Yamamoto, T and Gotoh, M}, title = {What are the factors contributing to failure in improvement of subjective symptoms following silodosin administration in patients with benign prostatic hyperplasia? Investigation using a pressure-flow study.}, journal = {Neurourology and urodynamics}, volume = {32}, number = {3}, pages = {266-270}, doi = {10.1002/nau.22286}, pmid = {22907775}, issn = {1520-6777}, mesh = {Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Aged ; Aged, 80 and over ; Humans ; Indoles/*therapeutic use ; Lower Urinary Tract Symptoms/diagnosis/*drug therapy/physiopathology ; Male ; Middle Aged ; Predictive Value of Tests ; Pressure ; Prospective Studies ; Prostatic Hyperplasia/diagnosis/*drug therapy/physiopathology ; Risk Factors ; Surveys and Questionnaires ; Time Factors ; Treatment Failure ; Urinary Bladder/*drug effects/physiopathology ; Urinary Bladder, Overactive/diagnosis/*drug therapy/physiopathology ; Urodynamics/*drug effects ; }, abstract = {AIMS: To investigate the factors responsible for failure in improvement of subjective symptoms following silodosin treatment on the basis of findings of a pressure-flow study (PFS).

METHODS: A post hoc analysis of a prospective study to investigate the efficacy of silodosin in patients with BPH was conducted, and 104 patients were analyzed. The patients were administered silodosin 8 mg/day for 4 weeks. At the baseline and after treatment, subjective symptoms were evaluated using the IPSS and OABSS. A PFS was conducted to measure storage and voiding function. The patients were divided into two groups: good responders (GR), patients with 25% or more improvement in IPSS, and poor responders (PR), <25% improvement. The clinical and objective findings for the two groups were compared.

RESULTS: The mean IPSS and OABSS significantly improved in GR, but no significant improvement was observed in PR. PFS analysis revealed that all voiding and storage function parameters improved significantly in GR. Although PR showed a significant improvement in the voiding function parameters, it did not show significant changes in the storage function. Involuntary detrusor contraction (IDC) resolved in 68.6% of the patients in GR and in only 30% of the patients in PR, thereby showing a significant difference in the remedial effect between the two groups.

CONCLUSIONS: The findings suggest that insufficient improvement in storage function is a contributing factor to the failure in improvement of subjective symptoms after silodosin treatment in patients with BPH.}, } @article {pmid22907070, year = {2012}, author = {Sánchez-Muñoz, A and Román-Jobacho, A and Pérez-Villa, L and Sánchez-Rovira, P and Miramón, J and Pérez, D and Sáez, MI and de Luque, V and Medina, L and Ramírez-Tortosa, CL and Vicioso, L and Medina, JA and Ribelles, N and Alba, E}, title = {Male breast cancer: immunohistochemical subtypes and clinical outcome characterization.}, journal = {Oncology}, volume = {83}, number = {4}, pages = {228-233}, doi = {10.1159/000341537}, pmid = {22907070}, issn = {1423-0232}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms, Male/*classification/metabolism/pathology ; Carcinoma, Basal Cell/classification/metabolism/pathology ; Carcinoma, Ductal, Breast/classification/metabolism/pathology ; Carcinoma, Lobular/classification/metabolism/pathology ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {AIM: The aim of this study was to assess the molecular subtype profiles of male breast cancer (MBC) and subsequent clinical outcome using a validated 6-marker immunohistochemical panel.

METHODS: A total of 43 cases of MBC were examined retrospectively using a semiquantitative immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (Her2), epidermal growth factor receptor and cytokeratin 5/6. Patients were classified into the following categories: luminal A, luminal B, Her2-positive or basal-like subtypes.

RESULTS: The median age of patients was 63 years (r: 32-89). The predominant histology was invasive ductal carcinoma (91%). Only 1 patient had advanced breast cancer at diagnosis. Ninety-three percent were ER-positive and 84% were PR-positive. Two patients had tumors that were ER- and PR-negative. The distribution of tumor molecular subtypes was 19 (44%) luminal A, 22 (51%) luminal B and 2 (5%) basal-like. The Her2-positive tumor subtype was not identified. The clinicopathological characteristics did not differ significantly between tumor subtypes A and B. There were no significant differences in 6-year disease-free survival (74 vs. 82%, p = 0.77) or overall survival (74 vs. 82%, p = 0.69) between luminal A and luminal B subtypes, respectively.

CONCLUSION: The most common subtypes in our cohort of MBC were luminal B followed by luminal A, and no differences were found between both tumor subtypes in terms of clinicopathologic characteristics and patient outcome.}, } @article {pmid22903908, year = {2012}, author = {Doron, G and Moulding, R and Nedeljkovic, M and Kyrios, M and Mikulincer, M and Sar-El, D}, title = {Adult attachment insecurities are associated with obsessive compulsive disorder.}, journal = {Psychology and psychotherapy}, volume = {85}, number = {2}, pages = {163-178}, doi = {10.1111/j.2044-8341.2011.02028.x}, pmid = {22903908}, issn = {2044-8341}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Analysis of Variance ; Anxiety Disorders/*epidemiology/psychology ; Case-Control Studies ; Catastrophization ; Cross-Sectional Studies ; Depressive Disorder, Major/*epidemiology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; Interpersonal Relations ; Interview, Psychological ; Male ; Middle Aged ; Models, Psychological ; *Object Attachment ; Obsessive-Compulsive Disorder/*epidemiology/psychology ; Psychiatric Status Rating Scales ; Psychological Theory ; Young Adult ; }, abstract = {OBJECTIVES: Obsessive compulsive disorder (OCD) is one of the most disabling and highly prevalent anxiety disorders (ADs). Current cognitive models of OCD implicate views about the self and world in the maintenance of the disorder. However, little research has focused on issues that may lead to vulnerability to such views. In particular, a person's attachment insecurities (attachment anxiety, avoidance) may be important risk factors increasing the likelihood of such non-adaptive perceptions (Doron & Kyrios, 2005).

DESIGN: Participants meeting criteria for OCD were compared with cohorts meeting criteria for other ADs and healthy controls on a range of measures including adult attachment, OC symptoms, cognitions, and mood.

METHODS: Diagnosis of the clinical groups was established using the Anxiety Disorders Interview Schedule for DSM-IV (Brown, Di Nardo, & Barlow, 1994). The clinical relevance of attachment insecurities was ascertained by comparing their prevalence in an OCD sample (N = 30), an ADs sample (N = 20), and a community sample (N = 32).

RESULTS: Attachment anxiety was significantly higher in individuals with OCD, even when controlling for depression.

CONCLUSIONS: Addressing attachment anxiety in individuals presenting with OCD may be important for enhancing therapeutic outcomes. However, findings are based on cross-sectional data that preclude conclusions relating to causal influence.}, } @article {pmid22903863, year = {2013}, author = {Figueiredo, P and Toussaint, HM and Vilas-Boas, JP and Fernandes, RJ}, title = {Relation between efficiency and energy cost with coordination in aquatic locomotion.}, journal = {European journal of applied physiology}, volume = {113}, number = {3}, pages = {651-659}, pmid = {22903863}, issn = {1439-6327}, mesh = {Acceleration ; Adult ; Arm/physiology ; Biomechanical Phenomena/physiology ; Energy Metabolism/*physiology ; Humans ; Locomotion/physiology ; Male ; Muscle Fatigue/physiology ; Oxygen Consumption/physiology ; Psychomotor Performance/*physiology ; Swimming/*physiology ; Young Adult ; }, abstract = {The aim of this study was to establish the relationships between the intracycle velocity variation (IVV) and Froude efficiency (η(T)), energy cost (C), and index of coordination (IdC) throughout a 200-m freestyle race. Ten male international level swimmers performed a maximum 200 m front crawl swim. Performance was recorded with four below- and two above-water synchronized cameras. Oxygen consumption was measured continuously during the effort, and blood samples were collected before and after the test. IdC, body center of mass' IVV (x, y and z), and η(T) were also calculated. For assessing C swimmers performed also 50, 100 and 150 m at the same pace as in the 200-m splits to capture blood lactate samples after each 50-m lap of the 200-m effort. Swimmers attained a stable IVV (x, y, and z), as fatigue development along the 200-m effort induced a decrease in velocity, stroke length, stroke frequency, η(T), and an increase of IdC. Direct relationships between C and IdC for the second and fourth lap were found: R = 0.63 and R = 0.69 (P < 0.05), respectively. Computing partial correlation, also IdC and η(T) in the first lap were significantly correlated (R = -0.63, P < 0.05). IdC and η(T) showed to be significant for the within-subjects correlation (R = -0.45, P = 0.01), and IdC and C for the between-subjects correlation (R = 0.66, P = 0.04). Patterns of coordination modified during the 200-m event in response to the task constraints, observed by the changes in the other studied parameters, and allowing the IVV stability along the effort.}, } @article {pmid22903146, year = {2012}, author = {Szajnik, M and Szczepanski, MJ and Elishaev, E and Visus, C and Lenzner, D and Zabel, M and Glura, M and DeLeo, AB and Whiteside, TL}, title = {17β Hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma.}, journal = {Gynecologic oncology}, volume = {127}, number = {3}, pages = {587-594}, pmid = {22903146}, issn = {1095-6859}, support = {N01HB37165/HL/NHLBI NIH HHS/United States ; P01 CA109688/CA/NCI NIH HHS/United States ; N01-HB37165/HB/NHLBI NIH HHS/United States ; P0-1-CA109688/CA/NCI NIH HHS/United States ; }, mesh = {17-Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism ; Apoptosis ; Biomarkers, Tumor/antagonists & inhibitors/*metabolism ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Ovarian Neoplasms/*enzymology/mortality/pathology ; Prognosis ; RNA, Small Interfering/genetics ; }, abstract = {OBJECTIVE: 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in the growth and progression of this tumor.

METHODS: Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined.

RESULTS: HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogeneous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown.

CONCLUSION: HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression.}, } @article {pmid22900944, year = {2012}, author = {Dennhag, I and Gibbons, MB and Barber, JP and Gallop, R and Crits-Christoph, P}, title = {Do supervisors and independent judges agree on evaluations of therapist adherence and competence in the treatment of cocaine dependence?.}, journal = {Psychotherapy research : journal of the Society for Psychotherapy Research}, volume = {22}, number = {6}, pages = {720-730}, pmid = {22900944}, issn = {1468-4381}, support = {R01 DA012249/DA/NIDA NIH HHS/United States ; U18 DA007090/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Clinical Competence/*statistics & numerical data ; Cocaine-Related Disorders/*therapy ; Cognitive Behavioral Therapy/methods/statistics & numerical data ; Counseling/methods/statistics & numerical data ; Female ; Guideline Adherence/*statistics & numerical data ; Health Personnel/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Observer Variation ; Practice Guidelines as Topic ; Psychotherapy/*methods/statistics & numerical data ; Randomized Controlled Trials as Topic ; }, abstract = {The current study examined the agreement between supervisors' and independent judges' evaluations of therapist adherence and competence in three treatments of cocaine dependence: supportive expressive therapy (SE), cognitive therapy CT), and individual drug counseling (IDC). We used data from The National Institute on Drug Abuse Collaborative Cocaine Treatment Study (n = 295). Trained and experienced supervisors and independent judges rated treatment fidelity. At the therapist level of analysis, the agreement between supervisors' and independent judges' ratings was weak for SE competence, CT adherence, and CT competence. Moderate relations were found for IDC adherence and competence. Supervisors consistently rated adherence and competence more positively than judges in CT and IDC. The potential bias in supervisors' ratings is discussed.}, } @article {pmid22897789, year = {2013}, author = {Ling, H and Liu, ZB and Xu, LH and Xu, XL and Liu, GY and Shao, ZM}, title = {Malignant calcification is an important unfavorable prognostic factor in primary invasive breast cancer.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {9}, number = {2}, pages = {139-145}, doi = {10.1111/j.1743-7563.2012.01572.x}, pmid = {22897789}, issn = {1743-7563}, mesh = {Adult ; Aged ; Breast Neoplasms/complications/mortality/*pathology/therapy ; Calcinosis/*diagnosis/etiology ; Carcinoma, Ductal, Breast/complications/mortality/*secondary/therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/complications/mortality/*secondary/therapy ; Lung Neoplasms/complications/mortality/*secondary/therapy ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {AIMS: To explore the clinical characteristics and prognostic value of malignant calcification in operable breast cancer.

METHODS: A total of 721 patients with invasive ductal carcinoma were divided into two groups based on whether malignant calcifications were observed on mammograms. The association of calcification with pathological features and survival were evaluated. The relative importance of each of the potential prognostic variables was tested using a Cox regression analysis.

RESULTS: Compared with tumors without calcification, those with calcification had a larger tumor size, more lymph node involvement, lower estrogen and progesterone receptor expression and higher human epithelial growth factor receptor 2 expression. The 8-year relapse-free survival was lower for patients with calcifications than for those without (77.5 vs 89.2%, P < 0.01). The 8-year overall survival for patients with calcifications was 82.2% compared with 91.9% for those without (P < 0.01). In multivariate analysis, node status, existence of calcification and tumor size were demonstrated to have a prognostic value for relapse-free survival. The node status, existence of calcifications and estrogen receptor status were also prognostic factors for overall survival.

CONCLUSION: Mammographic calcification is a poor prognostic factor for patients with invasive ductal carcinoma. Its prognostic value is second only to axillary node status and greater than the other factors evaluated. Thus, breast cancers with calcifications should be regarded as high risk when determining adjuvant treatment.}, } @article {pmid22895267, year = {2012}, author = {Duan, X and Sneige, N and Gullett, AE and Prieto, VG and Resetkova, E and Andino, LM and Wu, Y and Gilcrease, MZ and Bedrosian, I and Dawood, S and Arun, B and Albarracin, CT}, title = {Invasive paget disease of the breast: clinicopathologic study of an underrecognized entity in the breast.}, journal = {The American journal of surgical pathology}, volume = {36}, number = {9}, pages = {1353-1358}, doi = {10.1097/PAS.0b013e318259ef7f}, pmid = {22895267}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/secondary ; Combined Modality Therapy ; Dermis/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Paget's Disease, Mammary/*diagnosis/therapy ; Treatment Outcome ; }, abstract = {Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.}, } @article {pmid22894137, year = {2012}, author = {dos Santos, PB and Zanetti, JS and Ribeiro-Silva, A and Beltrão, EI}, title = {Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {104}, pmid = {22894137}, issn = {1746-1596}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*chemistry/mortality/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/mortality/secondary/therapy ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Integrin beta1/*analysis ; Kaplan-Meier Estimate ; Middle Aged ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Time Factors ; Tissue Array Analysis ; Up-Regulation ; Vascular Endothelial Growth Factor A/analysis ; }, abstract = {BACKGROUND: The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS).

METHODS: Through tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance.

RESULTS: β1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding β1 integrin expression.

CONCLUSIONS: Considering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer.

VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871.}, } @article {pmid22893571, year = {2012}, author = {Hoffman, G}, title = {Embodied cognition for autonomous interactive robots.}, journal = {Topics in cognitive science}, volume = {4}, number = {4}, pages = {759-772}, doi = {10.1111/j.1756-8765.2012.01218.x}, pmid = {22893571}, issn = {1756-8765}, mesh = {*Artificial Intelligence ; *Cognition ; Electronic Data Processing ; Humans ; Neural Networks, Computer ; *Robotics ; User-Computer Interface ; }, abstract = {In the past, notions of embodiment have been applied to robotics mainly in the realm of very simple robots, and supporting low-level mechanisms such as dynamics and navigation. In contrast, most human-like, interactive, and socially adept robotic systems turn away from embodiment and use amodal, symbolic, and modular approaches to cognition and interaction. At the same time, recent research in Embodied Cognition (EC) is spanning an increasing number of complex cognitive processes, including language, nonverbal communication, learning, and social behavior. This article suggests adopting a modern EC approach for autonomous robots interacting with humans. In particular, we present three core principles from EC that may be applicable to such robots: (a) modal perceptual representation, (b) action/perception and action/cognition integration, and (c) a simulation-based model of top-down perceptual biasing. We describe a computational framework based on these principles, and its implementation on two physical robots. This could provide a new paradigm for embodied human-robot interaction based on recent psychological and neurological findings.}, } @article {pmid22891313, year = {2012}, author = {Tanaka, H and Abe, S and Huda, N and Tu, L and Beam, MJ and Grimes, B and Gilley, D}, title = {Telomere fusions in early human breast carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {35}, pages = {14098-14103}, pmid = {22891313}, issn = {1091-6490}, mesh = {Breast/cytology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Female ; Fibroblasts/cytology ; Foreskin/cytology ; Gene Expression Regulation, Neoplastic/*genetics ; Genomic Instability/genetics ; Humans ; Male ; Neoplasm Staging ; Retroelements/*genetics ; Telomerase/genetics ; Telomere/*genetics ; Tissue Banks ; }, abstract = {Several lines of evidence suggest that defects in telomere maintenance play a significant role in the initiation of genomic instability during carcinogenesis. Although the general concept of defective telomere maintenance initiating genomic instability has been acknowledged, there remains a critical gap in the direct evidence of telomere dysfunction in human solid tumors. To address this topic, we devised a multiplex PCR-based assay, termed TAR (telomere-associated repeat) fusion PCR, to detect and analyze chromosome end-to-end associations (telomere fusions) within human breast tumor tissue. Using TAR fusion PCR, we found that human breast lesions, but not normal breast tissues from healthy volunteers, contained telomere fusions. Telomere fusions were detected at similar frequencies during early ductal carcinoma in situ and in the later invasive ductal carcinoma stage. Our results provide direct evidence that telomere fusions are present in human breast tumor tissue and suggest that telomere dysfunction may be an important component of the genomic instability observed in this cancer. Development of this robust method that allows identification of these genetic aberrations (telomere fusions) is anticipated to be a valuable tool for dissecting mechanisms of telomere dysfunction.}, } @article {pmid22888636, year = {2012}, author = {Davalieva, K and Kiprijanovska, S and Broussard, C and Petrusevska, G and Efremov, GD}, title = {Proteomic analysis of infiltrating ductal carcinoma tissues by coupled 2-D DIGE/MS/MS analysis.}, journal = {Molekuliarnaia biologiia}, volume = {46}, number = {3}, pages = {469-480}, pmid = {22888636}, issn = {0026-8984}, mesh = {Aged ; Biomarkers, Tumor/*genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Hydrogen-Ion Concentration ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics ; Protein Interaction Mapping ; Proteome/*analysis/genetics ; Proteomics ; Tandem Mass Spectrometry ; }, abstract = {There is a growing interest in protein expression profiling aiming to identify novel diagnostic markers in breast cancer. Proteomic approaches such as two-dimensional differential gel electrophoresis coupled with tandem mass spectrometry analysis (2-D DIGE/MS/MS) have been used successfully for the identification of candidate biomarkers for screening, diagnosis, prognosis and monitoring of treatment response in various types of cancer. Identifying previously unknown proteins of potential clinical relevance will ultimately help in reaching effective ways to manage the disease. We analyzed breast cancer tissues from five tumor and five normal tissue samples from ten breast cancer subjects with infiltrating ductal carcinoma (IDC) by 2-D DIGE using two types of immobilized pH gradient (IPG) strips: pH 3-10 and pH 4-7. From all the spots detected, differentially expressed (p < 0.05 and ratio > 2) were 50 spots. Of these, 39 proteins were successfully identified by MS, representing 29 different proteins. Ten proteins were overexpressed in the tumor samples. The 2-D DIGE/MS/MS analysis revealed an increase in the expression levels in tumor samples of several proteins not previously associated with breast cancer, such as: macrophage-capping protein (CAPG), phosphomannomutase 2 (PMM2), ATPase ASN1, methylthioribose-1-phosphate isomerase (MRI1), peptidyl-prolyl cis-trans isomerase FKBP4, cellular retinoic acid-binding protein 2 (CRABP2), lamin B1 and keratin, type II cytoskeletal 8 (KRT8). Ingenuity Pathway Analysis (IPA) revealed highly significant (p = 10(-26)) interactions between the identified proteins and their association with cancer. These proteins are involved in many diverse pathways and have established roles in cellular metabolism. It remains the goal of future work to test the suitability of the identified proteins in samples of larger and independent patient groups.}, } @article {pmid22887771, year = {2012}, author = {Liao, S and Desouki, MM and Gaile, DP and Shepherd, L and Nowak, NJ and Conroy, J and Barry, WT and Geradts, J}, title = {Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast.}, journal = {Genes, chromosomes & cancer}, volume = {51}, number = {12}, pages = {1067-1078}, pmid = {22887771}, issn = {1098-2264}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; R21 CA106676/CA/NCI NIH HHS/United States ; 5P30CA016056-34/CA/NCI NIH HHS/United States ; R21CA106676/CA/NCI NIH HHS/United States ; }, mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Comparative Genomic Hybridization ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; }, abstract = {Only a minority of intraductal carcinomas of the breast give rise to stromally invasive disease. We microdissected 206 paraffin blocks representing 116 different cases of low-grade ductal carcinoma in situ (DCIS). Fifty-five were pure DCIS (PD) cases without progression to invasive carcinoma. Sixty-one cases had a small invasive component. DNA was extracted from microdissected sections and hybridized to high-density bacterial artificial chromosome arrays. Array comparative genomic hybridization analysis of 118 hybridized DNA samples yielded data on 69 samples that were suitable for further statistical analysis. This cohort included 20 pure DCIS cases, 25 mixed DCIS (MD), and 24 mixed invasive carcinoma samples. PD cases had a higher frequency of DNA copy number changes than MD cases, and the latter had similar DNA profiles compared to paired invasive carcinomas. Copy number changes on 13 chromosomal arms occurred at different rates in PD versus MD lesions. Eight of 19 candidate genes residing at those loci were confirmed to have differential copy number changes by quantitative PCR. NCOR2/SMRT and NR4A1 (both on 12q), DYNLRB2 (16q), CELSR1, UPK3A, and ST13 (all on 22q) were more frequently amplified in PD. Moreover, NCOR2, NR4A1, and DYNLRB2 showed more frequent copy number losses in MD. GRAP2 (22q) was more often amplified in MD, whereas TAF1C (16q) was more commonly deleted in PD. A multigene model comprising these candidate genes discriminated between PD and MD lesions with high accuracy. These findings suggest that the propensity to invade the stroma may be encoded in the genome of intraductal carcinomas.}, } @article {pmid22886719, year = {2013}, author = {Siegfried, JD and Morales, A and Kushner, JD and Burkett, E and Cowan, J and Mauro, AC and Huggins, GS and Li, D and Norton, N and Hershberger, RE}, title = {Return of genetic results in the familial dilated cardiomyopathy research project.}, journal = {Journal of genetic counseling}, volume = {22}, number = {2}, pages = {164-174}, pmid = {22886719}, issn = {1573-3599}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/*genetics ; Genetic Counseling ; *Genetic Predisposition to Disease ; Genetic Testing ; Humans ; United States ; }, abstract = {The goal of the Familial Dilated Cardiomyopathy (FDC) Research Project, initiated in 1993, has been to identify and characterize FDC genetic cause. All participating individuals have been consented for the return of genetic results, an important but challenging undertaking. Since the inception of the Project we have enrolled 606 probands, and 269 of these had 1670 family members also enrolled. Each subject was evaluated for idiopathic dilated cardiomyopathy (IDC) and pedigrees were categorized as familial or sporadic. The coding regions of 14 genes were resequenced in 311 to 324 probands in five studies. Ninety-two probands were found to carry nonsynonymous rare variants absent in controls, and with Clinical Laboratory Improvement Amendment of 1988 (CLIA) compliant protocols, relevant genetic results were returned to these probands and their consented relatives by study genetic counselors and physicians in 353 letters. In 10 of the 51 families that received results >1 year ago, at least 23 individuals underwent CLIA confirmation testing for their family's rare variant. Return of genetic results has been successfully undertaken in the FDC Research Project. This report describes the methods utilized in the process of returning research results. We use this information as a springboard for providing guidance to other genetic research groups and proposing future directions in this arena.}, } @article {pmid22883668, year = {2012}, author = {Zhao, XJ and Li, B and Xu, JP and Wang, ZY and Wang, L and Zhu, HY and Chu, XH}, title = {[Invasive ductal carcinomas of breast showing partial reversed cell polarity are associated with lymphatic tumor spread].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {41}, number = {5}, pages = {305-308}, doi = {10.3760/cma.j.issn.0529-5807.2012.05.005}, pmid = {22883668}, issn = {0529-5807}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Papillary/metabolism/*pathology ; *Cell Polarity ; Female ; Humans ; Immunohistochemistry ; *Lymphatic Metastasis ; Middle Aged ; Mucin-1/metabolism ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVE: To investigate the relationship between partial reversed cell polarity (PRCP) and lymphatic tumor spread in invasive ductal carcinoma (IDC), not othervise specified (NOS).

METHODS: Immunohistochemistry (EnVision method) was used to examine the expression of epithelial membrane antigen (EMA) and the reversed cell polarity in 199 cases of IDC.

RESULTS: Of the 199 cases, including five cases with micropapillary differentiation,30 cases with PRCP and 164 cases of IDC-NOS (without micropapillary differentiation and/or PRCP), lymphovascular invasion was seen in four (4/5), 13(43.3%) and 30 cases (18.3%) respectively; nodal metastasis was seen in four (4/5), 19 (63.3%) and 56 cases (34.1%) respectively. The rates of lymphovascular invasion and nodal metastasis were significantly higher in IDC with PRCP or IMPC than IDC-NOS (P = 0.00); there was however no significant difference between IDC with PRCP and IMPC for lymphovascular invasion and nodal metastasis (P = 0.18, P = 0.64).

CONCLUSIONS: IDC with PRCP, similar to IMPC, is more likely to show lymphovascular invasion and nodal metastasis. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.}, } @article {pmid22883666, year = {2012}, author = {Ying, JM and Liu, XY and Guo, L and Xie, YQ and Lü, N}, title = {[Analysis of HER2 status in breast carcinoma using fully automated HER2 staining and fluorescence in-situ hybridization technology].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {41}, number = {5}, pages = {296-300}, doi = {10.3760/cma.j.issn.0529-5807.2012.05.003}, pmid = {22883666}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Breast Neoplasms/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Female ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prospective Studies ; Quality Control ; Receptor, ErbB-2/*genetics ; Young Adult ; }, abstract = {OBJECTIVE: To determine human epidermal growth factor receptor 2 (HER2) status in breast carcinoma by the techniques of a fully automated immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), to compare the concordance of protein expression with gene amplification and to explore the optimization in process quality control.

METHODS: A prospective study of invasive breast cancer specimens excised between May 2009 and April 2011 at the Cancer Hospital, Chinese Academy of Medical Sciences was conducted by automated IHC staining with the new 4B5 rabbit monoclonal antibody and FISH. An evaluation was performed according to the ASCO/CAP guidelines (2007) and Chinese guidelines (2009). The gene amplification status of 740 cases were detected by FISH.

RESULTS: A total of 2420 cases of breast invasive ductal carcinoma without pre-operation therapy were tested by automated IHC. 551 cases (22.8%) were scored as positive (3+), 664 cases (27.4%) as equivocal (2+), and 1205 cases (49.8%) as negative (1+/0). Gene amplification was detected in 98.0% (242/247) HER2 protein expression positive (3+) cases and in 13.6% (53/389) equivocal (2+) cases. One of 247 (0.4%) HER2 expression 3+ cases and 5 of 389 (1.3%) HER2 expression 2+ cases were equivocal for gene amplification. No gene amplification was detected in expression negative (1+/0) cases by FISH (0/104). The overall concordance between IHC and FISH was 98.6% [(242 + 104)/(247 + 104)].

CONCLUSIONS: There is a high concordance rate between automated IHC with 4B5 rabbit monoclonal antibody and FISH results for assessing the HER2 gene amplification status in surgically-excised breast cancer specimens, suggesting that automated IHC with 4B5 antibody can provide a reliable method to detect HER2 overexpression for eligibility of HER2 targeted therapy.}, } @article {pmid22877570, year = {2013}, author = {Ergül, N and Kadıoğlu, H and S Yıldız, and Başkaya Yücel, S and Aydın, M}, title = {Autoamputation of breast caused by invasive ductal carcinoma.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {32}, number = {3}, pages = {199-200}, doi = {10.1016/j.remn.2012.06.005}, pmid = {22877570}, issn = {2253-8070}, mesh = {Breast Neoplasms/complications/*pathology ; Carcinoma, Ductal, Breast/complications/*pathology ; Female ; Humans ; Middle Aged ; }, } @article {pmid22876347, year = {2012}, author = {Sharma, V and Shivalingaiah, S and Peng, Y and Euhus, D and Gryczynski, Z and Liu, H}, title = {Auto-fluorescence lifetime and light reflectance spectroscopy for breast cancer diagnosis: potential tools for intraoperative margin detection.}, journal = {Biomedical optics express}, volume = {3}, number = {8}, pages = {1825-1840}, pmid = {22876347}, issn = {2156-7085}, abstract = {This study investigates the use of two spectroscopic techniques, auto-fluorescence lifetime measurement (AFLM) and light reflectance spectroscopy (LRS), for detecting invasive ductal carcinoma (IDC) in human ex vivo breast specimens. AFLM used excitation at 447 nm with multiple emission wavelengths (532, 562, 632, and 644 nm), at which auto-fluorescence lifetimes and their weight factors were analyzed using a double exponent model. LRS measured reflectance spectra in the range of 500-840 nm and analyzed the spectral slopes empirically at several distinct spectral regions. Our preliminary results based on 93 measured locations (i.e., 34 IDC, 31 benign fibrous, 28 adipose) from 6 specimens show significant differences in 5 AFLM-derived parameters and 9 LRS-based spectral slopes between benign and malignant breast samples. Multinomial logistic regression with a 10-fold cross validation approach was implemented with selected features to classify IDC from benign fibrous and adipose tissues for the two techniques independently as well as for the combined dual-modality approach. The accuracy for classifying IDC was found to be 96.4 ± 0.8%, 92.3 ± 0.8% and 96 ± 1.3% for LRS, AFLM, and dual-modality, respectively.}, } @article {pmid22870824, year = {2012}, author = {Song, BI and Lee, SW and Jeong, SY and Chae, YS and Lee, WK and Ahn, BC and Lee, J}, title = {18F-FDG uptake by metastatic axillary lymph nodes on pretreatment PET/CT as a prognostic factor for recurrence in patients with invasive ductal breast cancer.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {53}, number = {9}, pages = {1337-1344}, doi = {10.2967/jnumed.111.098640}, pmid = {22870824}, issn = {1535-5667}, mesh = {Adult ; Aged ; Biological Transport ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology/therapy ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; *Positron-Emission Tomography ; Recurrence ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {UNLABELLED: This study assessed the maximum standardized uptake value of metastatic axillary lymph nodes in patients with invasive ductal breast cancer (IDC) to determine the pretreatment prognostic value of (18)F-FDG PET/CT for disease-free survival (DFS).

METHODS: Sixty-five female IDC patients who had undergone pretreatment (18)F-FDG PET/CT and had pathologically confirmed axillary lymph node involvement without distant metastasis were enrolled. All patients showed complete remission after first-line treatment. To obtain nodal SUVmax, a transaxial image representing the highest (18)F-FDG uptake was carefully selected and a region of interest was manually drawn on the (18)F-FDG-accumulating lesion. Clinicopathologic parameters such as age, TNM stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and primary-tumor and nodal SUVmax on PET were analyzed for their usefulness in predicting recurrence. Combinatorial effects and interactions between variables that were significant by univariate analysis were examined using multivariate Cox proportional-hazards models.

RESULTS: Twelve of 65 patients (18.5%) experienced recurrence during follow-up (median follow-up, 36 mo; range, 21-57 mo). Nodal SUVmax was significantly higher in patients with recurrence than in those who were disease-free (recurrence group: 5.2 ± 2.3, vs. disease-free group: 1.9 ± 1.9, P < 0.0001). A receiver-operating-characteristic curve demonstrated a nodal SUVmax of 2.8 (sensitivity, 91.7%; specificity, 86.8%; area under the curve, 0.890) to be the optimal cutoff for predicting DFS. Univariate analysis revealed that T stage, N stage, estrogen receptor status, and primary-tumor and nodal SUVmax correlated significantly with DFS. Among these 5 variables, only nodal SUVmax was found to be a single determinant of DFS by multivariate analysis (hazard ratio, 31.54; 95% confidence interval, 2.66-373.39; P = 0.0065).

CONCLUSION: Nodal SUVmax on pretreatment (18)F-FDG PET/CT may be an independent prognostic factor for disease recurrence in patients with IDC.}, } @article {pmid22866167, year = {2012}, author = {Carcoforo, P and Raiji, MT and Langan, RC and Lanzara, S and Portinari, M and Maestroni, U and Palini, GM and Zanzi, MV and Bonazza, S and Pedriali, M and Feo, CV and Stojadinovic, A and Avital, I}, title = {Infiltrating lobular carcinoma of the breast presenting as gastrointestinal obstruction: a mini review.}, journal = {Journal of Cancer}, volume = {3}, number = {}, pages = {328-332}, pmid = {22866167}, issn = {1837-9664}, abstract = {One in twelve American women will develop breast cancer, with infiltrating lobular carcinoma (ILC) comprising approximately 15% of these cases. The incidence of ILC has been increasing over the last several decades. It has been hypothesized that this increase is associated with combined replacement hormonal therapy. Although pathologically distinct from infiltrating ductal carcinoma (IDC), ILC is treated in the same manner as IDC. However, ILC demonstrates significantly different patterns of late local recurrence and distant metastasis. The incidence of extra-hepatic gastrointestinal metastases is reported to be 6% to 18%, with stomach being most common. Herein, we present a brief review of the literature and a typical case involving ILC initially presenting as a small bowel obstruction. Evidence suggests that the late clinical patterns of ILC are distinctly separate from IDC and physicians need be cognizant of its late local recurrence and unique late metastatic pattern. Different follow up strategy should be entertained in patients with ILC.}, } @article {pmid22865198, year = {2012}, author = {Orgüç, Ş and Başara, I and Coşkun, T and Pekindil, G}, title = {Three-dimensional vascular mapping of the breast by using contrast-enhanced MRI: association of unilateral increased vascularity with ipsilateral breast cancer.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {18}, number = {5}, pages = {454-459}, doi = {10.4261/1305-3825.DIR.5280-11.2}, pmid = {22865198}, issn = {1305-3612}, mesh = {Adult ; Aged ; Breast/*blood supply/pathology ; Breast Neoplasms/diagnosis/*pathology ; Case-Control Studies ; Female ; *Gadolinium DTPA ; Humans ; *Imaging, Three-Dimensional ; Magnetic Resonance Angiography/*methods ; Middle Aged ; Neovascularization, Pathologic/diagnosis ; Reference Values ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {PURPOSE: We aimed to retrospectively compare three-dimensional vascular maps of both breasts obtained by dynamic magnetic resonance imaging (MRI) and determine the association of one-sided vascular prominence with ipsilateral breast cancer.

MATERIALS AND METHODS: MRI was performed using gadolinium in 194 cases. Two readers scored vascular density using maximum intensity projections (MIPs). Dynamic fat-saturated T1-weighted gradientecho MIPs were acquired. Two readers evaluated the MIPs, and vessels greater than 2 mm in diameter and longer than 3 cm were counted. The difference in vessel numbers detected in the two breasts determined the score.

RESULTS: A total of 54 patients had malignant lesions (prevalence, 28%), including invasive ductal carcinoma (n=40), invasive mixed ductal-lobular carcinoma (n=5), invasive lobular carcinoma (n=3), ductal carcinoma in situ (n=3), mucinous carcinoma (n=1), medullary carcinoma (n=1), and leukemic metastasis (n=1). In 62 patients, there were benign lesions (fibroadenomas, fibrocysts), and four patients had inflammation (granulomatous mastitis in two patients, breast tuberculosis in two patients). There were 78 normal cases. When a difference of at least two vessels was scored as vascular asymmetry, the sensitivity, specificity, positive likelihood ratio (+LR), and negative (-LR) of unilaterally increased vascularity associated with ipsilateral malignancy were 69%, 92%, 8.72, and 0.34, respectively. When four infection and three post-operative cases with vascular asymmetry were excluded; prevalence, specificity, and +LR increased to 29%, 97%, and 22.8, respectively, with the same sensitivity and -LR. Differences in mean vascularity scores were evaluated with regard to tumor size. T1 and T2 tumors were not significantly different from each other. The mean score of T3 tumors differed significantly from T1 and T2 tumors.

CONCLUSION: MRI vascular mapping is an effective method for determining breast tissue vascularization. Ipsilateral increased vascularity was commonly associated with malignant breast lesions.}, } @article {pmid22864797, year = {2012}, author = {Cheng, CW and Liu, YF and Yu, JC and Wang, HW and Ding, SL and Hsiung, CN and Hsu, HM and Shieh, JC and Wu, PE and Shen, CY}, title = {Prognostic significance of cyclin D1, β-catenin, and MTA1 in patients with invasive ductal carcinoma of the breast.}, journal = {Annals of surgical oncology}, volume = {19}, number = {13}, pages = {4129-4139}, doi = {10.1245/s10434-012-2541-x}, pmid = {22864797}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cyclin D1/genetics/*metabolism ; Female ; Follow-Up Studies ; Histone Deacetylases/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Laser Capture Microdissection ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Trans-Activators ; beta Catenin/genetics/*metabolism ; }, abstract = {BACKGROUND: To investigate markers for predicting breast cancer progression, we performed a candidate gene-based study that assessed expression change of three genes, cyclin D1, β-catenin, and metastasis-associated protein-1 (MTA1), involving in aggressive phenotypes of cancerous cells, namely hyperproliferation, epithelial-mesenchymal transition, and global transcriptional regulation.

METHODS: Specimens were from 150 enrolled female patients, with invasive ductal carcinoma, followed up for more than 10 years. mRNA expression of cyclin D1, β-catenin, and MTA1 in cancerous and noncancerous cells microdissected from the primary tumor site was determined by quantitative real-time PCR. The relationship between mRNA expression levels of the genes and clinicopathologic features was assessed by statistical analysis. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with log-rank test and a multivariate Cox regression model.

RESULTS: Cyclin D1 was shown to be overexpressed in late-stage breast cancer (stage III/IV). Breast cancer with lymph node metastasis (LNM) showed significantly higher frequency of overexpressed cyclin D1, β-catenin, and MTA1 (P < 0.05). Patients carrying greater numbers of overexpressed genes had joint effects on increased risk in tumors of advanced stages (P (trend) = 0.03) and LNM (P (trend) < 0.01). In the LNM-negative group, patients whose tumors with greater number of cyclin D1, β-catenin, and MTA1 overexpressions were associated with poorer clinical outcomes, with hazard ratio of 14.79 for OS (P = 0.015) and 7.54 for DFS (P = 0.015) using multivariate Cox regression analysis during the 10-year follow-up.

CONCLUSIONS: Higher expression of cyclin D1, β-catenin, and MTA1 mRNAs in breast cancers may prove effective in predicting unfavorable outcomes of breast cancer.}, } @article {pmid22862431, year = {2012}, author = {Matsumoto, K and Tanaka, H and Tatsumi, K and Kaneko, A and Tsuji, T and Ryo, K and Kawai, H and Hirata, K}, title = {Regional heterogeneity of systolic dysfunction is associated with ventricular dyssynchrony in patients with idiopathic dilated cardiomyopathy and narrow QRS complex.}, journal = {Echocardiography (Mount Kisco, N.Y.)}, volume = {29}, number = {10}, pages = {1201-1210}, doi = {10.1111/j.1540-8175.2012.01791.x}, pmid = {22862431}, issn = {1540-8175}, mesh = {Cardiomyopathy, Dilated/complications/diagnostic imaging/*physiopathology ; Echocardiography, Three-Dimensional/*methods ; *Electrocardiography ; Female ; Follow-Up Studies ; Heart Ventricles/diagnostic imaging/*physiopathology ; Humans ; Male ; Middle Aged ; Stroke Volume ; Systole ; Ventricular Dysfunction, Left/diagnostic imaging/etiology/*physiopathology ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: Regional heterogeneity of left ventricular (LV) contraction, known as dyssynergy, in idiopathic dilated cardiomyopathy (IDC) patients has been previously reported, but no comprehensive analysis of this abnormality has been made. The purpose of this study was to test the hypothesis that regional heterogeneity of systolic dysfunction is associated with LV dyssynchrony in IDC patients with a narrow QRS complex using novel three-dimensional (3D) speckle-tracking strain.

METHODS: We studied 54 consecutive IDC patients with ejection fraction (EF) of 34 ± 12% and QRS duration of 102 ± 13 msec (all <120 msec), and 30 age-matched normal controls. The 3D speckle-tracking LV dyssynchrony (LV dyssynchrony index) was quantified from all 16 LV sites to determine the standard deviation (SD) of time-to-peak strain. Similarly, regional heterogeneity of LV systolic function (LV dyssynergy index) was quantified from all 16 LV sites to establish the SD of peak 3D speckle-tracking strain.

RESULTS: The LV dyssynergy and dyssynchrony indices of IDC patients were significantly larger than those of normal controls. Furthermore, IDC patients showed significantly higher Z-scores for septum and inferior regions than for the free wall (3.34 ± 1.21 vs. 1.69 ± 1.06 and 2.79 ± 1.30 vs. 1.69 ± 1.06, respectively, P < 0.001). An important findings of multivariable analysis was that the LV dyssynergy index (β = 0.69, P < 0.001) and LVEF (β = -0.34, P = 0.001) were independent determinants of the LV dyssynchrony index.

CONCLUSION: 3D speckle-tracking strain revealed that the myocardial systolic dysfunction of IDC patients with a narrow QRS complex has a marked heterogeneous regional distribution. This regional heterogeneity as well as systolic dysfunction is thought to lead to LV dyssynchrony.}, } @article {pmid22852824, year = {2012}, author = {Keshtgar, MR and Eaton, DJ and Reynolds, C and Pigott, K and Davidson, T and Gauter-Fleckenstein, B and Wenz, F}, title = {Pacemaker and radiotherapy in breast cancer: is targeted intraoperative radiotherapy the answer in this setting?.}, journal = {Radiation oncology (London, England)}, volume = {7}, number = {}, pages = {128}, pmid = {22852824}, issn = {1748-717X}, mesh = {Aged, 80 and over ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/surgery ; Combined Modality Therapy ; Female ; Humans ; *Intraoperative Care ; Mastectomy ; *Pacemaker, Artificial ; Prognosis ; Sentinel Lymph Node Biopsy ; }, abstract = {We present the case of an 83 year old woman with a cardiac pacemaker located close in distance to a subsequently diagnosed invasive ductal carcinoma of the left breast. Short range intraoperative radiotherapy was given following wide local excision and sentinel node biopsy. The challenges of using ionising radiation with pacemakers is also discussed.}, } @article {pmid22842170, year = {2012}, author = {Ranade, KJ and Nerurkar, AV and Phulpagar, MD and Shirsat, NV}, title = {Myoepithelial expression of Fas and strong nuclear expression of FasL in epithelial cells: a marker for risk stratification of breast cancer.}, journal = {Indian journal of cancer}, volume = {49}, number = {1}, pages = {60-65}, doi = {10.4103/0019-509X.98921}, pmid = {22842170}, issn = {1998-4774}, mesh = {Adolescent ; Adult ; Apoptosis ; *Breast Neoplasms/genetics/metabolism/pathology ; Epithelium/metabolism ; *Fas Ligand Protein/genetics/metabolism ; Female ; *Fibroadenoma/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Muscle Cells/metabolism ; Retrospective Studies ; Risk Factors ; *fas Receptor/genetics/metabolism ; }, abstract = {AIM: The clinical significance of Fas and FasL in hormone-sensitive carcinomas has been reported. Our objective was to evaluate the expression of apoptosis-regulating genes Fas and FasL in Indian breast cancer and fibroadenoma patients in relation to hormone receptor status.

STUDY DESIGN: Retrospective.

MATERIALS AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with invasive ductal carcinoma (IDC) and 32 female patients with fibroadenoma were studied. Expression of Fas and FasL was evaluated using immunohistochemical staining method.

STATISTICAL ANALYSIS: Fisher's exact test and nonparametric correlation test (Spearman rank correlation test) were performed.

RESULT: Fas was detected in 97% of the fibroadenomas and there was a slight decrease in levels of expression with histological grades of IDC. The expression of FasL was detected in 75% fibroadenomas and its expression increased in IDC. There was no correlation between Fas, FasL expression and hormone receptor status. Strong expression of Fas in myoepithelial cells was noted in 12 out of 32 fibroadenoma cases.

CONCLUSION: Expression of Fas and FasL alone is unlikely to be important as a predictive factor as they express in both normal and malignant breast epithelium. But strong expression of Fas in myoepithelial cells along with strong nuclear expression of FasL in epithelial cells of fibroadenoma could be useful as an early predictive factor for onset of malignancy.}, } @article {pmid22833438, year = {2012}, author = {Bonzanini, M and Morelli, L and Bonandini, EM and Leonardi, E and Pertile, R and Dalla Palma, P}, title = {Cytologic features of triple-negative breast carcinoma.}, journal = {Cancer cytopathology}, volume = {120}, number = {6}, pages = {401-409}, doi = {10.1002/cncy.21207}, pmid = {22833438}, issn = {1934-6638}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; Breast/metabolism/*pathology ; Breast Neoplasms/diagnosis/metabolism/*pathology ; Diagnosis, Differential ; Female ; Humans ; Logistic Models ; Lymphocytes/pathology ; Middle Aged ; Multivariate Analysis ; Necrosis ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Triple-negative breast cancer (TNBC) is distinct from other breast cancers, because the tumor cells lack estrogen and progesterone receptors (hormone receptors) and also are negative for human epidermal growth factor receptor 2 (HER2). They comprise a heterogeneous group of tumors with various histologic features and clinical behaviors. High-grade, invasive ductal carcinoma not otherwise specified is the most frequent type, and a substantial fraction of TNBCs belongs to the basal-like tumor type. The purpose of this study was to determine whether some cytologic features could predict the triple phenotype of breast carcinoma.

METHODS: Fine-needle aspiration cytology samples of 62 TNBCs were compared with samples of 82 hormone receptor-positive, high-grade, invasive carcinomas (HRBC) and with samples of 33 hormone receptor-negative, HER2 positive, invasive carcinomas (HER2BC) for the following cytomorphologic features: cellularity, necrosis, lymphocytes, syncytial clusters, tubular/ductal-like clusters, large bare nuclei, streaming within the clusters, and calcifications. Moreover, single cell features, such as cellular borders, cytoplasm, cytoplasmic vacuoles, nuclear pleomorphism, nucleoli, and type of chromatin pattern, were evaluated. Descriptive analyses and 2 multivariate regression models were performed to compare TNBC, HRBC, and HER2BC and to identify the cytologic factors that were associated with tumor type.

RESULTS: TNBCs were more likely to have an abundant necrotic background, many lymphocytes, many syncytial clusters, and ill defined cell borders than non-TNBCs. A tubular/ductal pattern was observed only rarely in TNBCs. Multivariate logistic analysis indicated a 90.8% probability of identifying TNBC versus HRBC by the following cytologic variables: lymphocytes, ill defined cell borders and syncytial clusters, tubular/ductal clusters, cytoplasmic vacuoles, and cellular pleomorphism; whereas there was a 77.5% probability of identifying TNBC rather than HER2BC by the following variables: cellularity, ill defined cellular borders and syncytial clusters, and tubular/ductal clusters.

CONCLUSIONS: Although TNBCs embrace a heterogeneous group of tumors, in this study, they exhibited some common cytologic features that can help to distinguish them from other high-grade breast carcinomas in daily practice.}, } @article {pmid22824957, year = {2012}, author = {Liu, Z and Wang, Y and Wang, S and Zhang, J and Zhang, F and Niu, Y}, title = {Nek2C functions as a tumor promoter in human breast tumorigenesis.}, journal = {International journal of molecular medicine}, volume = {30}, number = {4}, pages = {775-782}, doi = {10.3892/ijmm.2012.1069}, pmid = {22824957}, issn = {1791-244X}, mesh = {Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia/*genetics ; NIMA-Related Kinases ; Protein Serine-Threonine Kinases/*genetics ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Up-Regulation ; }, abstract = {The serine⁄threonine kinase Nek2 has been proposed as a requirement for the progression of breast cancer. The aim of this study was to investigate the expression of Nek2C, which is a splice variant of Nek2, and the role it plays in the different stages of breast cancer. We investigated the role of Nek2C in the MCF10 breast cancer cell lines, MCF10A, MCF10AT, MCF10DCIS.com and MCF10CA1a, using RNA interference and plasmid transfection, as well as breast tissue samples of normal breast tissue (NBT), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). We detected the mRNA Nek2C expression levels in the MCF10 cell lines and in human breast samples. Our results revealed that the mRNA expression of Nek2C was significantly upregulated in the MCF10DCIS.com and MCF10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). As expected, the Nek2C downregulation, using RNA interference, decreased the survival, invasion and migration of MCF10DCIS.com and MCF10CA1a cells. Consistent with these results, the Nek2C upregulation in MCF10A and MCF10AT cells using plasmid transfection increased the survival ability of these cells. Our results also revealed a correlation between Nek2C mRNA expression levels and tumor grade. Taken together, our findings suggest that Nek2C plays a signicficant role in breast cancer development and that Nek2C inhibition may be a useful therapeutic approach to targeting human breast tumors.}, } @article {pmid22819916, year = {2012}, author = {Nanashima, A and Shibata, K and Nakayama, T and Abo, T and Nonaka, T and Fukuda, D and Fukuoka, H and Hidaka, S and Takeshita, H and Sawai, T and Yasutake, T and Nagayasu, T}, title = {Relationship between microvessel count and clinicopathological characteristics and postoperative survival in patients with pancreatic carcinoma.}, journal = {Hepato-gastroenterology}, volume = {59}, number = {118}, pages = {1964-1969}, doi = {10.5754/hge10618}, pmid = {22819916}, issn = {0172-6390}, mesh = {Antigens, CD34/analysis ; Disease-Free Survival ; Female ; Gastrostomy ; Humans ; Immunohistochemistry ; Japan ; Kaplan-Meier Estimate ; Male ; Microvessels/immunology/*pathology ; Middle Aged ; Multivariate Analysis ; *Pancreatectomy/adverse effects/methods/mortality ; Pancreatic Neoplasms/*blood supply/mortality/pathology/*surgery ; Pancreaticoduodenectomy ; Pancreaticojejunostomy ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy.

METHODOLOGY: CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients.

RESULTS: Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15).

CONCLUSIONS: Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.}, } @article {pmid22811748, year = {2012}, author = {Santos Araújo, Mdo C and Farias, IL and Gutierres, J and Dalmora, SL and Flores, N and Farias, J and de Cruz, I and Chiesa, J and Morsch, VM and Chitolina Schetinger, MR}, title = {Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2012}, number = {}, pages = {676984}, pmid = {22811748}, issn = {1741-4288}, abstract = {Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.}, } @article {pmid22810087, year = {2012}, author = {Kwast, AB and Groothuis-Oudshoorn, KC and Grandjean, I and Ho, VK and Voogd, AC and Menke-Pluymers, MB and van der Sangen, MJ and Tjan-Heijnen, VC and Kiemeney, LA and Siesling, S}, title = {Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences.}, journal = {Breast cancer research and treatment}, volume = {135}, number = {1}, pages = {271-280}, doi = {10.1007/s10549-012-2160-z}, pmid = {22810087}, issn = {1573-7217}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Disease-Free Survival ; Female ; Humans ; *Neoplasm Metastasis ; *Neoplasm Recurrence, Local ; Netherlands ; Receptors, Estrogen/metabolism ; Receptors, Progesterone ; Risk Factors ; }, abstract = {Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78-1.06, >3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences.}, } @article {pmid22808818, year = {2011}, author = {Pudasaini, S and Talwar, OP}, title = {Study of fine needle aspiration cytology of breast lumps and its histopathological correlation in Pokhara Valley.}, journal = {Nepal Medical College journal : NMCJ}, volume = {13}, number = {3}, pages = {208-212}, pmid = {22808818}, issn = {2676-1319}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Cohort Studies ; Female ; Humans ; Middle Aged ; Nepal ; Sensitivity and Specificity ; Young Adult ; }, abstract = {Breast carcinoma is the leading cause of cancer death in women. Most of the time breast carcinoma presents as breast lump. Fine Needle Aspiration Cytology (FNAC) is a convenient and rapid preoperative diagnostic procedure. This is a prospective and correlative study done in department of Pathology of Manipal Teaching Hospital, Pokhara from December 2003 to December 2005. FNAC was performed in patients presenting with breast lump and its findings were correlated with histopathological findings. Out of total 343 cases of breast FNAC, 73 cases had histopathology correlation. Age group of the patient ranged from 17 to 84 years. Breast lumps were most commonly seen in age group 21 to 30 years which comprises of benign lesions. Maximum number of malignancy (26%) was seen in age group 41 to 50 years. Out of 73 cases, malignancy was seen in 15 cases (20.5%). The most common carcinoma was Invasive Ductal Carcinoma (IDC) with 46.7% cases. With correlation of FNAC and histopathology, the sensitivity and specificity of both benign and malignant lesions were high. In malignant lesions, the sensitivity and specificity were 93.3% and 100% respectively. FNAC is a safe diagnostic procedure in the preoperative diagnosis of breast lumps in our setting. It gives the accurate result with proper technique and interpretation.}, } @article {pmid22808723, year = {2012}, author = {Havriluk, R}, title = {Do expert swimmers have expert technique? Comment on "Arm coordination and performance level in the 400-m front crawl" by Schnitzler, Seifert, and Chollet (2011).}, journal = {Research quarterly for exercise and sport}, volume = {83}, number = {2}, pages = {359-362}, doi = {10.1080/02701367.2012.10599868}, pmid = {22808723}, issn = {0270-1367}, mesh = {Athletic Performance/*physiology ; Humans ; Male ; Swimming/*physiology ; Upper Extremity/*physiology ; }, abstract = {In a recent article by Schnitzler, Seifert, and Chollet (2011), they used an index of coordination (IdC) to quantify arm synchronization in swimming, which has become a practical standard to measure gaps (negative IdC) and overlaps (positive IdC) in arm propulsion. Their previous work supported an increase in IdC as swimming velocity and performance level increase, consistent with mechanics and physiology. Their recent study showed a lower IdC for expert swimmers than for recreational swimmers and concluded "catch-up coordination can be an efficient coordination mode. "In the hopes of preventing coaches and swimmers from using this finding to justify "catch-up stroke", other explanations are suggested.}, } @article {pmid22807966, year = {2012}, author = {Xie, B and Zheng, H and Lan, H and Cui, B and Jin, K and Cao, F}, title = {Synchronous bilateral Paget's disease of the breast: A case report.}, journal = {Oncology letters}, volume = {4}, number = {1}, pages = {83-85}, pmid = {22807966}, issn = {1792-1074}, abstract = {Synchronous bilateral Paget's disease of the nipple is extremely rare. In the present study, we report a case of synchronous bilateral Paget's disease in a 45-year-old woman who had a medical history of gastric cancer. The patient presented with a 6-month history of eczema and itching in both nipples. Mammography and ultrasonography did not reveal any mass lesions in the bilateral breast, and computed tomography and bone scintigraphy showed no site of distant metastasis. The patient was scheduled for mastectomy and sentinel node biopsy. The histological diagnosis was Paget's disease of the breast with no evidence of underlying invasive ductal carcinoma or ductal carcinoma in situ of the breast tissue. There was no metastasis in either of the sentinel nodes. Immunohistochemical staining showed a negative expression of oestrogen and progesterone receptors. The patient has not received chemotherapy, radiotherapy or hormonal therapy. The patient has been disease-free for 7 months following surgery.}, } @article {pmid22807946, year = {2012}, author = {Seker, D and Seker, G and Ozturk, E and Bayar, B and Kulacoglu, H}, title = {An incidentally detected breast cancer on tc-99m MIBI cardiac scintigraphy.}, journal = {Journal of breast cancer}, volume = {15}, number = {2}, pages = {252-254}, pmid = {22807946}, issn = {2092-9900}, abstract = {Tc-99m methoxyisobutylisonitrile (MIBI) scintigraphy is generally used as a second-line diagnostic tool for obscured breast lesions. When the entire field of view is examined carefully, it is often possible to detect additional lesions unrelated to the initial intent and purpose of the examination. Herein we present a case of breast cancer incidentally detected by cardiac Tc-99m MIBI scintigraphy. An area of uptake was detected in the breast during a cardiac imaging test. Further evaluation of this lesion revealed a histopathological diagnosis of invasive ductal carcinoma of the breast. Sensitivity of this scintigraphic technique is not enough sufficient to use this test as a screening test for breast cancer, but it may provide supplemental information. Since it is not uncommon to find incidental lesions during imaging studies, examination of the image field may help clinicians find otherwise unrecognized or undiagnosed pathologies.}, } @article {pmid22807945, year = {2012}, author = {Sun, WY and Lee, KH and Lee, HC and Ryu, DH and Park, JW and Yun, HY and Song, YJ}, title = {Synchronous bilateral male breast cancer: a case report.}, journal = {Journal of breast cancer}, volume = {15}, number = {2}, pages = {248-251}, pmid = {22807945}, issn = {2092-9900}, abstract = {Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed.}, } @article {pmid22807934, year = {2012}, author = {Jang, SM and Han, H and Jang, KS and Jun, YJ and Jang, SH and Min, KW and Chung, MS and Paik, SS}, title = {The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas.}, journal = {Journal of breast cancer}, volume = {15}, number = {2}, pages = {172-180}, pmid = {22807934}, issn = {2092-9900}, abstract = {PURPOSE: Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas.

METHODS: We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis.

RESULTS: Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively).

CONCLUSION: GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.}, } @article {pmid22805492, year = {2012}, author = {Cao, AY and Huang, L and Wu, J and Lu, JS and Liu, GY and Shen, ZZ and Shao, ZM and Di, GH}, title = {Tumor characteristics and the clinical outcome of invasive lobular carcinoma compared to infiltrating ductal carcinoma in a Chinese population.}, journal = {World journal of surgical oncology}, volume = {10}, number = {}, pages = {152}, pmid = {22805492}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Lobular/mortality/*pathology ; Female ; Humans ; Middle Aged ; Proportional Hazards Models ; }, abstract = {BACKGROUND: We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC) using a large database.

METHODS: Clinicopathologic features, overall survival (OS), and recurrence/metastasis-free survival (RFS) were compared between 2,202 patients with IDC and 215 patients with ILC.

RESULTS: ILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P=0.001). The frequencies of recurrence/metastasis (P = 0.980) and death (P = 0.064) were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months.

CONCLUSIONS: Chinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.}, } @article {pmid22797464, year = {2013}, author = {Yoo, EH and Kim, D}, title = {Predictors of postoperative antimuscarinics in women with mixed urinary incontinence after transobturator surgery.}, journal = {International urogynecology journal}, volume = {24}, number = {3}, pages = {401-406}, pmid = {22797464}, issn = {1433-3023}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Follow-Up Studies ; *Gynecologic Surgical Procedures ; Humans ; Incidence ; Middle Aged ; Muscarinic Antagonists/pharmacology/*therapeutic use ; Postoperative Period ; Retrospective Studies ; Risk Factors ; *Suburethral Slings ; Urinary Bladder, Overactive/physiopathology/*surgery ; Urinary Incontinence/physiopathology/*surgery ; Urodynamics/drug effects/physiology ; }, abstract = {INTRODUCTION AND HYPOTHESIS: The study sought to identify the risk factors of postoperative use of antimuscarinics after transobturator surgery in women with mixed urinary incontinence (MUI) displaying both urodynamic stress urinary incontinence (SUI) and involuntary detrusor contraction (IDC) with leakage in urodynamic study.

METHODS: The clinical data of 103 patients with MUI who underwent transobturator tape (TOT) sling surgery were retrospectively reviewed. The patients were followed at least a year. To determine risk factors for postoperative use of antimuscarinics, variables of only those with P values < 0.05 on univariate analysis were included in the multivariate logistic regression analysis with forward stepwise building.

RESULTS: Eight-four (81.6 %) of 103 patients were included in this study. The cure rate of urge urinary incontinence (UUI) was 69.0 % (58/84). Antimuscarinics were prescribed postoperatively in 22 (26.2 %) of 84 patients. Variables affecting postoperative use of antimuscarinics were age, parity, episode of any UUI, preoperative use of antimuscarinics, predominant urgency incontinence type, detrusor pressure at maximum flow, and Urogenital Distress Inventory 6. Increasing age and preoperative use of antimuscarinics increased the odds of postoperative use of antimuscarinics following TOT surgery.

CONCLUSION: Patients who were older and had taken antimuscarinics preoperatively were significantly associated with postoperative use of antimuscarinics.}, } @article {pmid22791767, year = {2012}, author = {Min, KW and Kim, DH and Do, SI and Sohn, JH and Chae, SW and Pyo, JS and Park, CH and Oh, YH and Jang, KS and Kim, HL and Kim, M}, title = {Diagnostic and prognostic relevance of Cullin1 expression in invasive ductal carcinoma of the breast.}, journal = {Journal of clinical pathology}, volume = {65}, number = {10}, pages = {896-901}, doi = {10.1136/jclinpath-2012-200847}, pmid = {22791767}, issn = {1472-4146}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/mortality ; Carcinoma, Ductal, Breast/*diagnosis/mortality ; Cullin Proteins/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; Tissue Array Analysis/methods ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Cullin1 (Cul1) is a matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins. This enzyme has recently been reported to play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours.

METHODS: 159 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were studied. Cul1 expression was analysed by immunohistochemical staining on a tissue microarray. The relationship between Cul1 expression and clinicopathological parameters was evaluated.

RESULTS: Tumour expression of Cul1 was correlated with prognostic factors such as high histological grade and p53 expression, and was also linked to negative ER and positive HER2 as therapeutic markers (all p<0.05). There was a significant association between poor overall survival and high Cul1 expression in both univariate and multivariate analyses (all p<0.05).

CONCLUSIONS: Cul1 expression was significantly associated with high-grade tumours and poor prognosis, suggesting that it may play a role in breast tumour progression. Cul1 expression may therefore be crucial for the prediction of disease outcome in breast cancer patients.}, } @article {pmid22789011, year = {2012}, author = {Ruan, JW and Liao, YC and Lua, I and Li, MH and Hsu, CY and Chen, JH}, title = {Human pituitary tumor-transforming gene 1 overexpression reinforces oncogene-induced senescence through CXCR2/p21 signaling in breast cancer cells.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {4}, pages = {R106}, pmid = {22789011}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Cellular Senescence/genetics ; Epithelial Cells/metabolism ; Female ; *Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Ligands ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogene Proteins p21(ras)/genetics/*metabolism ; Receptors, Interleukin-8B/*metabolism ; Securin/*genetics ; *Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {INTRODUCTION: hPTTG1 (human pituitary tumor-transforming gene 1) is an oncogene overexpressed in breast cancer and several other types of cancer. Increased hPTTG1 expression has been shown to be associated with poor patient outcomes in breast cancer. Although hPTTG1 overexpression plays important roles in promoting the proliferation, invasion, and metastasis of cancer cells, it also has been suggested to induce cellular senescence. Deciphering the mechanism by which hPTTG1 overexpression induces these contradictory actions in breast cancer cells is critical to our understanding of the role of hPTTG1 in breast cancer development.

METHODS: MCF-10A and MCF-7 cells were used to identify the mechanism of hPTTG1-induced senescence. The interplay between hPTTG1 overexpression and chemokine C-X-C motif receptor 2 (CXCR2)/p21-dependent senescence in tumor growth and metastasis of MCF-7 cells was investigated by orthotopic transplantation of severe combined immunodeficiency (SCID) mice. Additionally, human invasive ductal carcinoma (IDC) tissue arrays were used to confirm the hPTTG1/CXCR2/p21 axis established in vitro.

RESULTS: In this study, we investigated the mechanism of hPTTG1-induced senescence as well as its role in breast cancer progression and metastasis. Herein, we showed that hPTTG1 overexpression reinforced senescence through the CXCR2/p21 signaling. Furthermore, hPTTG1 overexpression activated NF-κB signaling to transactivate the expression of interleukin (IL)-8 and growth-regulated oncogene alpha (GROα) to execute CXCR2 signaling in MCF-7 cells. When CXCR2 expression was knocked down in hPTTG1-overexpressing MCF-7 cells, hPTTG1-induced senescence was abrogated by alleviating CXCR2-induced p21 expression. In a mouse model, CXCR2-mediated senescence limited hPTTG1-induced tumor growth and metastasis. Moreover, CXCR2 knockdown in hPTTG1-overexpressing MCF-7 tumors dramatically accelerated tumor growth and metastasis. Our in vitro and in vivo results demonstrated that hPTTG1 overexpression reinforces senescence through CXCR2 signaling, and the evasion of CXCR2/p21-dependent senescence was critical to hPTTG1 exerting its oncogenic potential. Interestingly, although CXCR2-dependent senescence restrained hPTTG1-induced tumor progression, when MCF-7 cells and hPTTG1-overexpressing MCF-7 cells were co-transplanted into the mammary fat pads of SCID mice, hPTTG1-overexpressing senescent cells created a metastasis-promoting microenvironment that promoted lung metastasis of the MCF-7 cells. Immunohistochemical analysis of human breast tumor samples also confirmed the importance of the hPTTG1/CXCR2 axis in promoting breast cancer metastasis.

CONCLUSIONS: Our findings provide novel molecular insights into hPTTG1-induced senescence and identify a novel mechanism by which hPTTG1 promotes metastasis by regulating the senescence-associated microenvironment.}, } @article {pmid22786991, year = {2012}, author = {Ferris-James, DM and Iuanow, E and Mehta, TS and Shaheen, RM and Slanetz, PJ}, title = {Imaging approaches to diagnosis and management of common ductal abnormalities.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {32}, number = {4}, pages = {1009-1030}, doi = {10.1148/rg.324115150}, pmid = {22786991}, issn = {1527-1323}, mesh = {Breast Diseases/*diagnosis/*therapy ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammary Glands, Human/*pathology ; Ultrasonography, Mammary/*methods ; }, abstract = {Ductal disease is an important, often overlooked, and poorly understood issue in breast imaging that results in delays in diagnosis and patient care. The differential diagnosis for an intraductal mass is broad and includes inspissated secretions, infection, hemorrhage, solitary or multiple papillomas, and malignancy. Each breast is composed of eight or more ductal systems, with most disease arising in the terminal ductal-lobular unit. Imaging evaluation of the ductal system usually entails a combination of mammography, galactography, ultrasonography (US), and in some cases magnetic resonance (MR) imaging. The most common finding with all modalities is ductal dilatation with a focal or diffuse abnormality. Benign diseases of the ducts include duct ectasia, blocked ducts, inflammatory infiltrates, periductal mastitis, apocrine metaplasia, intraductal papillomas, and papillomatosis. Malignant diseases of the ducts include ductal carcinoma in situ, invasive ductal carcinoma, and Paget disease. Most commonly performed with US or MR imaging guidance, percutaneous biopsy methods are helpful in diagnosis and management of ductal findings. Because most findings are smaller than 1 cm, located within a duct, and thus sometimes not visible after a single pass, vacuum-assisted devices help improve the accuracy of sampling.}, } @article {pmid22782361, year = {2014}, author = {Tamaki, K and Ishida, T and Tamaki, N and Kamada, Y and Uehara, K and Miyashita, M and Amari, M and Tadano-Sato, A and Takahashi, Y and Watanabe, M and McNamara, K and Ohuchi, N and Sasano, H}, title = {Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {3}, pages = {325-333}, doi = {10.1007/s12282-012-0387-5}, pmid = {22782361}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People ; Breast Neoplasms/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry/methods/standards ; Ki-67 Antigen/*analysis/*immunology/metabolism ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {BACKGROUND: It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion.

METHODS: We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index.

RESULTS: There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105).

CONCLUSIONS: A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.}, } @article {pmid22780975, year = {2012}, author = {Xu, Y and Fu, L and Gu, F and Ma, YJ}, title = {[Expression and significance of phosphorylated Girdin in breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {34}, number = {3}, pages = {205-209}, doi = {10.3760/cma.j.issn.0253-3766.2012.03.010}, pmid = {22780975}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Disease Progression ; Female ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Microfilament Proteins/*metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Phosphorylation ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Vesicular Transport Proteins/*metabolism ; }, abstract = {OBJECTIVE: To detect the expression of phosphorylated girdin (p-girdin) in breast cancer and its association with pathological characteristics and molecular subtypes of breast cancer.

METHODS: Immunohistochemical SP staining was used to investigate the expression of p-girdin in 27 cases of lobular hyperplasia of mammary gland, 61 cases of ductal carcinoma in situ (DCIS), and 94 cases of non-special type invasive carcinoma (IDC-NOS) of breast.

RESULTS: p-girdin was located in the cell cytoplasm and (or) nuclei in breast cancer. There was statistically a very significant difference among lobular hyperplasia, DCIS and IDC-NOS (χ2=26.724, P<0.001). Its cytoplasmic and nuclear reactivity were 25.9% (7/27), 39.3% (24/61), and 66.0% (62/94), respectively. The expression of p-girdin was positively associated with pathologic stage (r=0.204, P=0.049), lymph node metastasis (r=0.212, P=0.041) and HER2/neu (r=0.248, P=0.016). But no significant association was identified between p-girdin expression and histological grade (r=-0.015, P=0.918), age of patients (r=-0.011, P=0.918), tumor size (r=0.075, P=0.471), ER(r=0.071, P=0.498), PR (r=-0.050, P=0.634). Mann-Whitney test showed that p-girdin expression in luminal A, luminal B, triple negative and HER-2(+) type was significantly different (χ2=14.017, P=0.003). Among the four types, its positive rate was 55.8% (24/43), 95.8% (23/24), 66.7% (10/15), and 41.7% (5/12), respectively.

CONCLUSIONS: p-Girdin expression is closely correlated with the malignant progression of breast cancer. Its expression may have clinical value as a new target for the treatment of breast cancer.}, } @article {pmid22778998, year = {2012}, author = {Shah, DR and Tseng, WH and Martinez, SR}, title = {Treatment options for metaplastic breast cancer.}, journal = {ISRN oncology}, volume = {2012}, number = {}, pages = {706162}, pmid = {22778998}, issn = {2090-567X}, support = {UL1 RR024146/RR/NCRR NIH HHS/United States ; }, abstract = {Metaplastic breast cancer (MBC) is a malignancy characterized by the histologic presence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. MBC is rare relative to invasive ductal carcinoma (IDC), representing less than 1% of all breast cancers. Other than a lower rate of lymph node metastases, MBC tumors display poorer prognostic features relative to IDC. Due to its low incidence and pathological variability, the ideal treatment paradigm for MBC is unknown. Because of its rarity, MBC has been treated as a variant of IDC. Despite similar treatment regimens, however, patients with MBC have worse outcomes. Recent research is focused on biological differences between MBC and IDC and potential novel targets for chemotherapeutic agents. This paper serves as a summation of current literature on approaches to the multidisciplinary treatment of patients with MBC.}, } @article {pmid22777354, year = {2013}, author = {Scribner, KC and Behbod, F and Porter, WW}, title = {Regulation of DCIS to invasive breast cancer progression by Singleminded-2s (SIM2s).}, journal = {Oncogene}, volume = {32}, number = {21}, pages = {2631-2639}, pmid = {22777354}, issn = {1476-5594}, support = {R00 CA127462/CA/NCI NIH HHS/United States ; R01 CA111551/CA/NCI NIH HHS/United States ; R01CA111551/CA/NCI NIH HHS/United States ; 5R00CA127462-06/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/biosynthesis/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Caseins/biosynthesis/genetics ; *Cell Differentiation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Keratin-14/biosynthesis/genetics ; Keratin-18/biosynthesis/genetics ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Receptors, G-Protein-Coupled/biosynthesis/genetics ; Smoothened Receptor ; Transcription Factors/biosynthesis/genetics ; Transplantation, Heterologous ; Tumor Suppressor Proteins/biosynthesis/genetics ; Vimentin/biosynthesis/genetics ; }, abstract = {Singleminded-2s (SIM2s) is a member of the bHLH/PAS family of transcription factors and a key regulator of mammary epithelial cell differentiation. SIM2s is highly expressed in mammary epithelial cells and downregulated in human breast cancer. Loss of Sim2s causes aberrant mouse mammary ductal development, with features suggestive of malignant transformation, whereas overexpression of SIM2s promotes precocious alveolar differentiation in nulliparous mouse mammary glands, suggesting that SIM2s is required for establishing and enhancing mammary gland differentiation. To test the hypothesis that SIM2s regulates tumor cell differentiation, we analyzed SIM2s expression in human primary breast ductal carcinoma in situ (DCIS) samples and found that SIM2s is lost with progression from DCIS to invasive ductal cancer (IDC). Using a MCF10DCIS.COM progression model, we have shown that SIM2s expression is decreased in MCF10DCIS.COM cells compared with MCF10A cells, and reestablishment of SIM2s in MCF10DCIS.COM cells significantly inhibits growth and invasion both in vitro and in vivo. Analysis of SIM2s-MCF10DCIS.com tumors showed that SIM2s promoted a more differentiated tumor phenotype including the expression of a broad range of luminal markers (CSN2 (β-casein), CDH1 (E-cadherin), and KER18 (keratin-18)) and suppressed genes associated with stem cell maintenance and a basal phenotype (SMO (smoothened), p63, SLUG (snail-2), KER14 (keratin-14) and VIM (vimentin)). Furthermore, loss of SIM2s expression in MCF10DCIS.COM xenografts resulted in a more invasive phenotype and increased lung metastasis likely due to an increase in Hedgehog signaling and matrix metalloproteinase expression. Together, these exciting new data support a role for SIM2s in promoting human breast tumor differentiation and maintaining epithelial integrity.}, } @article {pmid22766516, year = {2012}, author = {Spano, JP and Lanoy, E and Mounier, N and Katlama, C and Costagliola, D and Heard, I}, title = {Breast cancer among HIV infected individuals from the ONCOVIH study, in France: therapeutic implications.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {48}, number = {18}, pages = {3335-3341}, doi = {10.1016/j.ejca.2012.05.019}, pmid = {22766516}, issn = {1879-0852}, mesh = {Adult ; Aged ; Alcohol Drinking/epidemiology ; Anti-HIV Agents/pharmacokinetics/therapeutic use ; Antineoplastic Agents/pharmacokinetics/therapeutic use ; Antiretroviral Therapy, Highly Active ; Breast Neoplasms/drug therapy/*epidemiology/radiotherapy/surgery ; Breast Neoplasms, Male/epidemiology/therapy ; CD4 Lymphocyte Count ; Carcinoma, Ductal, Breast/drug therapy/epidemiology/radiotherapy/surgery ; Combined Modality Therapy ; Cross-Sectional Studies ; Drug Interactions ; Estrogens ; Female ; France/epidemiology ; HIV Infections/drug therapy/*epidemiology ; Humans ; Immunocompromised Host ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multicenter Studies as Topic/statistics & numerical data ; Neoplasms, Hormone-Dependent/drug therapy/epidemiology/radiotherapy/surgery ; Progesterone ; Prospective Studies ; Risk Factors ; Smoking/epidemiology ; Surveys and Questionnaires ; Survival Rate ; Tumor Burden ; Viral Load ; }, abstract = {BACKGROUND: The cross-sectional ONCOVIH study prospectively enrolled HIV-infected adults and children with newly diagnosed malignancies in France in 2006.

METHOD: We report the characteristics HIV-infected patients with breast cancer from the ONCOVIH study. Standardised questionnaires included characteristics of HIV infection and malignancy. Survival was estimated using Kaplan-Meier estimates.

RESULTS: Overall, 21 patients with breast cancer (two men and 19 women) were included with a median age of 43.8 years, (range: 30.1-65.5). At time of tumour diagnosis, the median CD4 count was 384/mm(3) (range: 180-1039) the median duration of known seropositivity 7.7 years (range: 0-20.3); 14 patients were under combined antiretroviral therapy for a median duration of 5.7 years (range: 1.1-10.6), of whom 11 had a controlled viral load (<500 copies/mL). The median tumour size was 1.8 cm (range: 1.0-7.0). In women, 17 (89.5%) had invasive ductal carcinoma, 17 (89.5%) with HER2 negative receptors, 8 (42.1%) with ER+ expression, and 7 (36.8%) with PR+ expression. A majority of women received chemotherapy (73.7%), surgery (68.4%) and radiotherapy (57.9%). Their one-year survival rate was estimated as 77.8% (95%confidence interval (CI): 58.6-97.0%).

CONCLUSIONS: We discuss the risk of breast cancer in infected patients, and the importance of taking into account the different contributing factors for breast cancer in HIV-infected individuals.}, } @article {pmid22762532, year = {2012}, author = {Lin, Y and Zhong, Y and Guan, H and Zhang, X and Sun, Q}, title = {CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {31}, number = {1}, pages = {59}, pmid = {22762532}, issn = {1756-9966}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/*pathology/surgery ; CD24 Antigen/*biosynthesis ; Carcinoma, Ductal, Breast/*metabolism/*pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Hyaluronan Receptors/*biosynthesis ; Immunohistochemistry ; Middle Aged ; Phenotype ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Recurrence ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: Invasive ductal carcinoma is the most common type of breast malignancy, with varying molecular features and resistance to treatment. Although CD44+/CD24- cells are believed to act as breast cancer stem cells and to be linked to poor prognosis in some patients, the association between these cells and tumor recurrence or metastasis in all or some types of invasive ductal carcinoma is unclear.

METHODS: A total of 147 randomly selected primary and secondary invasive ductal carcinoma samples were assayed for expression of CD44, CD24, ER, PR, and Her2. The association between the proportions of CD44+/CD24- tumor cells and the clinico-pathological features of these patients was evaluated.

RESULTS: CD44+/CD24- tumor cells were detected in 70.1% of the tumors, with a median proportion of 5.8%. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement (P = 0.026) and PR status (P = 0.038), and was correlated with strong PR status in patients with recurrent or metastatic tumors (P = 0.046) and with basal-like features (p = 0.05). The median disease-free survival (DFS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 22.9 ± 2.2 months and 35.9 ± 3.8 months, and the median overall survival (OS) of patients with and without CD44(+)/CD24(-/low) tumor cells were 39.3 ± 2.6 months and 54.0 ± 3.5 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44(+)/CD24(-/low) tumor cells was strongly correlated with DFS and OS.

CONCLUSION: The prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44(+)/CD24(-) phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.}, } @article {pmid22761192, year = {2012}, author = {Soltan Dallal, MM and Yazdi, MH and Holakuyee, M and Hassan, ZM and Abolhassani, M and Mahdavi, M}, title = {Lactobacillus casei ssp.casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {11}, number = {2}, pages = {183-189}, pmid = {22761192}, issn = {1735-1502}, mesh = {Animals ; Breast Neoplasms/immunology/pathology/*therapy ; Carcinoma, Ductal, Breast/immunology/pathology/*therapy ; Coculture Techniques ; Cytokines/*metabolism ; Cytotoxicity, Immunologic ; Female ; Humans ; Immunotherapy/*methods ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; K562 Cells ; Killer Cells, Natural/*immunology ; Lacticaseibacillus casei/*immunology ; Mice ; Mice, Inbred BALB C ; Neoplasm Invasiveness ; *Probiotics ; Th1 Cells/*immunology ; Time Factors ; Tumor Burden ; }, abstract = {Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P<0.05) and increased the natural killer cells (NK) cytotoxicity in spleen cells culture of test mice (P<0.05). It has also been demonstrated that the growth rate of tumor in the test mice was decreased and their survival was significantly prolonged in comparison to the controls. Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.}, } @article {pmid22759568, year = {2012}, author = {Zhao, W and Dauwels, J and Niles, JC and Cao, J}, title = {Computational synchronization of microarray data with application to Plasmodium falciparum.}, journal = {Proteome science}, volume = {10 Suppl 1}, number = {Suppl 1}, pages = {S10}, pmid = {22759568}, issn = {1477-5956}, abstract = {BACKGROUND: Microarrays are widely used to investigate the blood stage of Plasmodium falciparum infection. Starting with synchronized cells, gene expression levels are continually measured over the 48-hour intra-erythrocytic cycle (IDC). However, the cell population gradually loses synchrony during the experiment. As a result, the microarray measurements are blurred. In this paper, we propose a generalized deconvolution approach to reconstruct the intrinsic expression pattern, and apply it to P. falciparum IDC microarray data.

METHODS: We develop a statistical model for the decay of synchrony among cells, and reconstruct the expression pattern through statistical inference. The proposed method can handle microarray measurements with noise and missing data. The original gene expression patterns become more apparent in the reconstructed profiles, making it easier to analyze and interpret the data. We hypothesize that reconstructed gene expression patterns represent better temporally resolved expression profiles that can be probabilistically modeled to match changes in expression level to IDC transitions. In particular, we identify transcriptionally regulated protein kinases putatively involved in regulating the P. falciparum IDC.

RESULTS: By analyzing publicly available microarray data sets for the P. falciparum IDC, protein kinases are ranked in terms of their likelihood to be involved in regulating transitions between the ring, trophozoite and schizont developmental stages of the P. falciparum IDC. In our theoretical framework, a few protein kinases have high probability rankings, and could potentially be involved in regulating these developmental transitions.

CONCLUSIONS: This study proposes a new methodology for extracting intrinsic expression patterns from microarray data. By applying this method to P. falciparum microarray data, several protein kinases are predicted to play a significant role in the P. falciparum IDC. Earlier experiments have indeed confirmed that several of these kinases are involved in this process. Overall, these results indicate that further functional analysis of these additional putative protein kinases may reveal new insights into how the P. falciparum IDC is regulated.}, } @article {pmid22748158, year = {2012}, author = {Davion, SM and Siziopikou, KP and Sullivan, ME}, title = {Cytokeratin 7: a re-evaluation of the 'tried and true' in triple-negative breast cancers.}, journal = {Histopathology}, volume = {61}, number = {4}, pages = {660-666}, doi = {10.1111/j.1365-2559.2012.04253.x}, pmid = {22748158}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; Humans ; Immunohistochemistry ; Keratin-7/analysis/*biosynthesis ; Middle Aged ; Tissue Array Analysis ; Triple Negative Breast Neoplasms/*metabolism ; }, abstract = {AIMS: Triple-negative breast cancers (TNBCs) are often poorly differentiated tumours that can present clinically as metastases of an unknown primary. Immunohistochemical panels are frequently used to determine the likelihood of a breast primary, but in this tumour subset cytokeratin (CK)7 may be the only positive finding. In this study we aimed to evaluate a commonly employed immunohistochemical panel using a large group of TNBCs (both basal-like and unclassified), and to analyse the CK7 staining patterns.

METHODS AND RESULTS: Tissue microarrays containing 138 TNBCs were stained with antibodies against CK7, CK20, gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin. CK5/6 staining was used to identify basal-like tumours. CK7 staining was notably heterogeneous, with 14.5% of all cases demonstrating ≤20% tumour cell staining. A greater proportion of basal-like TNBCs than of unclassified TNBCs showed focal staining. GCDFP-15 and mammaglobin were not expressed in the majority of TNBCs, and were less frequently positive in basal-like than in unclassified TNBCs.

CONCLUSION: TNBCs are commonly negative for most immunomarkers indicative of breast origin, with the exception of CK7. As about one in five TNBCs showed only focal CK7 positivity, use of this marker must be interpreted with caution, especially in small samples, so that the possibility of a breast primary is not overlooked.}, } @article {pmid24082688, year = {2012}, author = {Isolan, GR and Antunes, AC and Manfrim, J and Georg, AE and Falcetta, F}, title = {Intraosseouss degenerative cyst of the axis approached via transcervical extrapharyngeal avenue.}, journal = {Journal of craniovertebral junction & spine}, volume = {3}, number = {2}, pages = {70-72}, pmid = {24082688}, issn = {0974-8237}, abstract = {Intraosseous degenerative cysts (IDC) of the cervical spine are rare. IDC within C2 have been reported in three articles only. We report a patient with neck pain due to a IDC within C2. We discuss the differential diagnosis of these lesions and the surgical approaches to reach this complex anatomical region.}, } @article {pmid22741544, year = {2012}, author = {Choi, BB and Kim, SH and Kang, BJ and Lee, JH and Song, BJ and Jeong, SH and Yim, HW}, title = {Diffusion-weighted imaging and FDG PET/CT: predicting the prognoses with apparent diffusion coefficient values and maximum standardized uptake values in patients with invasive ductal carcinoma.}, journal = {World journal of surgical oncology}, volume = {10}, number = {}, pages = {126}, pmid = {22741544}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/metabolism/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/metabolism/therapy ; Diffusion Magnetic Resonance Imaging ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Image Processing, Computer-Assisted ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; *Multimodal Imaging ; Neoplasm Grading ; *Positron-Emission Tomography ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: FDG PET/CT and DWI are both functional modalities that indirectly represent the biological characteristics of cancer, but there are few studies exploring the association between the two modalities and prognostic factors. Our study attempted to evaluate the mutual association by comparing the prognostic factors, SUV(max) value of PET/CT, and ADC values associated with diffusion imaging in invasive ductal carcinoma (IDC) patients.

METHODS: Patients with pathologically confirmed IDC were recruited. There were 118 patients who underwent MRI, including DWI, FDG PET/CT, and immunohistochemical staining of the surgical specimen. Histologic analysis was done on tumor size, lymph node metastasis, expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and epidermal growth factor receptors (EGFR). The relationship among ADC values, SUV(max) and prognostic factors were evaluated.

RESULTS: There was significant association between the ADC value and ER-positive and HER2-negative expression. Significant associations were noted between SUV(max) and tumor size, lymph node metastasis, histologic grade, ER and PR expression, EGFR and Ki-67. However, there was no significant correlation between the ADC value and SUV(max).

CONCLUSIONS: Even though there was no correlation between ADC and SUV(max), both indexes are useful for predicting the prognosis of IDC.}, } @article {pmid22740976, year = {2012}, author = {Taromaru, GC and DE Oliveira, VM and Silva, MA and Montor, WR and Bagnoli, F and Rinaldi, JF and Aoki, T}, title = {Interaction between cyclooxygenase-2 and insulin-like growth factor in breast cancer: A new field for prevention and treatment.}, journal = {Oncology letters}, volume = {3}, number = {3}, pages = {682-688}, pmid = {22740976}, issn = {1792-1074}, abstract = {The objective of this study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and markers of cell proliferation and apoptosis, including, Bcl-2, Bax, Ki-67 and the type I insulin-like growth factor (IGF) receptor (IGF1-R) in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC), present in the same surgical specimen. A total of 110 cases were evaluated using tissue microarrays. Cases were classified in scores from 0 to 3 according to pre-defined methods. The results showed that the positivity rates were COX-2 in 87% of cases in DCIS and IDC; Bcl-2 in 55% of cases in DCIS and IDC; Bax in 23% of cases in IDC and 19% in DCIS, IGF-1 in 24% of cases in DCIS and IDC; and Ki-67 in 81% of cases in DCIS and IDC. We also observed a positive correlation between the expression of COX-2 and IGF1-R (p=0.045). Our results demonstrate a positive correlation between the expression of COX-2 and IGF1-R in DCIS and IDC, demonstrating that they are involved in breast cancer carcinogenesis. Further studies are required to prove the effectiveness of COX-2 and IGF1-R inhibitors for the prevention and treatment of breast cancer, as well as to explain their mechanism of action.}, } @article {pmid22740929, year = {2012}, author = {García Parra-Pérez, FA and Zavala-Pompa, A and Pacheco-Calleros, J and Cortés-Gutiérrez, EI and Cerda-Flores, RM and Lara-Miranda, S and Dávila-Rodríguez, MI}, title = {Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study.}, journal = {Oncology letters}, volume = {3}, number = {2}, pages = {445-449}, pmid = {22740929}, issn = {1792-1074}, abstract = {This pilot study analyzed and compared the presence of chromosome 8 aneusomy in Mexican women with breast cancer and adjacent, intraductal, proliferative lesions. To determine the chromosome 8 copy number, we performed fluorescence in situ hybridization in nine patients (1800 cells) who underwent mastectomy. We selected two tissue samples from each patient, one corresponding to the invasive ductal carcinoma (IDC) and the other adjacent to the intraductal proliferative lesion (IPL). Breast tissue from 17 autopsy samples (1700 cells) was used as a control. The number of cells with monosomy, disomy and polysomy per subject and type of tissue were compared among the three groups of tissue with the RxC statistical software package using 50,000 total replicates. Chromosome 8 aneusomy was found in 66 and 67% of cells from the IDC and IPL samples, respectively. Monosomy was detected significantly more frequently in IPL compared with IDC samples (49.11 vs. 27.11%; p=0.0000), whereas polysomy was significantly more frequent in IDC compared with IPL samples (40.11 vs. 16.99%; p=0.00000). Control cells showed 92.3% disomy. These findings suggest that polysomy of chromosome 8 is more frequently observed in IDC and that monosomy is more frequent in tissue of IPL. Therefore, monosomy may be considered as a primary preneoplastic event. Future studies should be performed to increase the amount of breast tissue with ductal proliferative changes and with cancer, in order to support the results of this pilot study.}, } @article {pmid22736333, year = {2012}, author = {Marras, F and Bozzano, F and Bentivoglio, G and Ugolotti, E and Biassoni, R and Moretta, L and De Maria, A}, title = {Receptor modulation and functional activation of human CD34+ Lin- -derived immature NK cells in vitro by Mycobacterium bovis Bacillus Calmette-Guerin (BCG).}, journal = {European journal of immunology}, volume = {42}, number = {9}, pages = {2459-2470}, doi = {10.1002/eji.201242375}, pmid = {22736333}, issn = {1521-4141}, mesh = {Antigens, CD34/genetics/*immunology/metabolism ; Antigens, Differentiation, T-Lymphocyte/genetics/metabolism ; BCG Vaccine/*immunology ; Cytotoxicity, Immunologic/genetics/*immunology ; Dendritic Cells/immunology/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics/immunology/metabolism ; Humans ; Interferon-gamma/genetics/immunology/metabolism ; Interleukin-10/genetics/immunology/metabolism ; Interleukin-18/genetics/immunology/metabolism ; K562 Cells ; Killer Cells, Natural/*immunology/metabolism ; Lymphocyte Activation ; Monocytes/immunology/metabolism ; Mycobacterium bovis/genetics/*immunology/metabolism ; Receptors, Immunologic/genetics/*immunology/metabolism ; Transforming Growth Factor beta/genetics/immunology/metabolism ; }, abstract = {It is not yet clear whether immature NK (iNK) cells are bystanders to or rather participate in immune responses to pathogens that may colocalize in areas of NK-cell maturation such as bone marrow or lymph nodes. Mycobacteria, including Bacillus Calmette-Guerin (BCG), have been shown to interact with peripheral NK cells and in vivo may colocalize in areas of iNK-cell development. We studied infection with BCG of human cord blood CD34(+) Lin(-)-derived cultures containing myelomonocytes and iNK cells in vitro. Increased iNK-cell DNAM-1 expression, transient natural cytotoxicity receptor modulation, and production of IFN-γ were observed. Transcriptional receptor modulation was associated to BCG challenge, which determined increased iNK-cell cytotoxic activity against tumor cell lines and also increased killing of immature dendritic cells (iDCs). No requirement for cell contact was recorded for BCG-induced iNK-cell activation, while cytokine production including IL-18, IL-10, GM-CSF, and TGF-β contributed to the observed effects. Thus, iNK cells are affected by mycobacteria in vitro and may contribute to shaping of adaptive mature innate responses through iDC-iNK cross-talk. In addition, iNK-cell activation by BCG may represent a novel additional mechanism contributing to the effects observed upon BCG administration in vivo.}, } @article {pmid22732836, year = {2012}, author = {Amin, M and Gabram, S and Bumpers, H and Landry, J and Jani, AB and Diaz, R and Rizzo, M}, title = {Feasibility of accelerated partial breast irradiation in a large inner-city public hospital.}, journal = {Annals of surgical oncology}, volume = {19}, number = {13}, pages = {4094-4098}, doi = {10.1245/s10434-012-2444-x}, pmid = {22732836}, issn = {1534-4681}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy/surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*radiotherapy/surgery ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast conserving therapy (BCT) that include breast conserving surgery followed by adjuvant radiation therapy has revolutioned medicine by allowing women to avoid mastectomy. Accelerated partial breast irradiation (APBI) has emerged as a valid alternative to whole-breast irradiation that requires a shorter time commitment. We report our novel experience with APBI at a large public hospital that serves low-income and potentially noncompliant patients.

METHODS: A retrospective chart review was conducted of women who underwent BCT for stage 0-IIA breast cancer from August 2007 to August 2010 treated with APBI with a brachytherapy catheter.

RESULTS: Twenty-four patients (20 African American) were considered for APBI. Average age was 61 years. Four patients could not undergo APBI for technical reasons and completed whole-breast irradiation over a 5 week period. Median follow-up was 19 months. Nine patients (37.5 %) had ductal carcinoma-in-situ, and 15 patients (62.5 %) had invasive ductal carcinoma with an average tumor size of 1.1 cm. All patients had negative margins of >2 mm. Two patients (8 %) treated with the brachytherapy catheter had in-breast tumor recurrence. Thus, all 24 patients initially identified for APBI successfully completed adjuvant radiotherapy.

CONCLUSIONS: Patient compliance with postoperative irradiation is key to minimize local recurrence after BCT for breast cancer. This success with a brachytherapy catheter in underserved women in a U.S. public hospital setting indicates that outcomes of compliance and complications are comparable to nationally published results.}, } @article {pmid22730654, year = {2012}, author = {Wang, SH and Li, DP and Zhang, YJ and Zhang, P and Zeng, LY and Pan, XY and Xu, KL and Huang, YH}, title = {[Effects of immature dendritic cells genetically modified to express sTNFR I on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) in allogeneic bone marrow transplantation mice].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {33}, number = {2}, pages = {88-93}, pmid = {22730654}, issn = {0253-2727}, mesh = {Animals ; Bone Marrow Transplantation/adverse effects/*methods ; Dendritic Cells/*immunology ; Female ; Graft vs Host Disease/*prevention & control ; *Graft vs Leukemia Effect ; Immune Tolerance ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, Tumor Necrosis Factor, Type I/*genetics ; Transplantation, Homologous ; }, abstract = {OBJECTIVE: To investigate the effect of immature dendritic cells (inDC) genetically modified to express sTNFR I on acute graft-versus-host disease (aGVHD) and the graft-versus-leukemia (GVL) effect ofter allogeneic bone marrow transplantation (allo-BMT) in leukemic mice and its mechanism.

METHODS: An EL4 leukemia allo-BMT model was established with the BALB/c (H-2d) donor mice (DM)and C57BL/6 (H-2b) recipient mice (RM). The RM received DM bone marrow (BM) cells at a 1:1 ratio with spleen cells intravenously via tail vein at 4 h after TBI. Fifty DM were separated randomly into five groups: (1) Group A: total body irradiation (TBI) group, (2) Group B: lymphoma cell leukemia group, (3) Group C: allo-BMT group, (4) Group D: pXZ9-DC group, (5) Group E: sTNFR I-DC group. Acute GVHD scores, incidence of leukemic cell infiltration, histopathological analysis, survival rate, and survival rate of the recipients were estimated after allo-BMT. Enzyme-linked immunosorbent assay (ELISA) method was used to detect cytokines (INF-gamma and IL-4) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.

RESULTS: (1) The mice in group A and group B all died of the BM failure and lymphoma cell leukemia, respectively. The mice in group C developed typical clinical signs of a GVHD after BMT with an average survival time(AST) of (11.50 +/- 3.50) d. The signs of aGVHD were less evident in the group D and E, and their AST (21.70 +/- 5.80 and 25.80 +/- 5.20 days, respectively) were all longer than that in group C (P < 0.05). AST of group E was the longest (P < 0.05). The mice in group B all died of leukemia within 18 days after engraftment of EL4 cells. There was was no significant difference in groups C, D and E in the incidence of leukemia (P > 0.05). (2) Serum IFN-gamma level reached peak value. At + 12 d, then decreased gradually in group C, D, and E, and then reached the nadir at +18 d post-BMT, with the lowest in group E (P < 0.05), and the level was significantly lower in group D than in group C (P < 0.05). After BMT, serum IL-4 level slightly decreased in group C, but gradually elevated in group D and E and reached their peak at +12 d, and even more significantly increased in group E (P < 0.05). There was no statistical significance in the pair wise comparison among three group (P < 0.05). (3) The average proportion of H-2d positive cells in RM was 95%-100% on day 30 post-BMT, with complete donor-type implantation.

CONCLUSION: Immature DC can induce immuno tolerance. Immature DC genetically modified to express sTNFR I has been shown to prevent acute GVHD in lethally irradiated mice reconstituted with allogeneic bone marrow grafts while maintaining the GVL response.}, } @article {pmid22729910, year = {2012}, author = {Hussain, SR and Babu, SG and Raza, ST and Singh, P and Ahmed, F and Naqvi, H and Mahdi, F}, title = {Screening of the c-kit gene missense mutation in invasive ductal carcinoma of breast among north Indian population.}, journal = {Molecular biology reports}, volume = {39}, number = {9}, pages = {9139-9144}, pmid = {22729910}, issn = {1573-4978}, mesh = {Adult ; Aged ; Amino Acid Sequence ; Base Sequence ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Exons ; Female ; Humans ; India ; Middle Aged ; Molecular Sequence Data ; *Mutation, Missense ; Neoplasm Grading ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-kit/*genetics ; }, abstract = {Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer deaths among females across the world, accounting for 23 % (1.38 million) of total new cancer cases and 14 % (0.45 million) of the total cancer deaths in 2008. c-kit is expressed in mast cell growth factor, cellular migration, proliferation, melanoblasts, haematopoietic progenitors and germ cells. We have designed our study with aim to explore the c-kit gene mutations in invasive ductal carcinoma (IDC) breast. To ascertain the range of mutations in exon 11, 13 and 17 of c-kit gene in 53 cases of IDC breast, we carried out PCR-SSCP followed by DNA sequencing. The mutation frequency of c-kit gene in exon 11, 13 and 17 were 9.43 % (5/53), 1.88 % (1/53) and 3.77 % (2/53), respectively. During our mutational analysis, we have detected five missense mutations in exon 11 (Pro551Leu, Glu562Val, Leu576Phe, His580Tyr and Phe584Leu), one missense mutation in exon 13 (Ser639Pro) and two missense mutations in exon 17 (Arg796Gly and Asn822Ser). It seems that c-kit mutations might participate in breast cancer pathogenesis and may be utilized as predictive marker, since the loss of c-kit positivity is generally linked with different types of breast cancer. Further molecular studies are necessary to validate the association of c-kit gene mutation in IDC breast pathogenesis.}, } @article {pmid22723076, year = {2012}, author = {de La Blanchardière, A and Boutemy, J and Thibon, P and Michon, J and Verdon, R and Cattoir, V}, title = {Clinical benefit of infectious diseases consultation: a monocentric prospective cohort study.}, journal = {Infection}, volume = {40}, number = {5}, pages = {501-507}, pmid = {22723076}, issn = {1439-0973}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Child ; Child, Preschool ; Communicable Diseases/*diagnosis/*therapy ; Female ; Humans ; Infectious Disease Medicine/*methods ; Male ; Middle Aged ; Multivariate Analysis ; Patient Compliance/statistics & numerical data ; Prospective Studies ; Referral and Consultation/*statistics & numerical data ; Treatment Outcome ; }, abstract = {PURPOSE: To determine the association of clinical outcomes with the adherence to Infectious Diseases Consultation (IDC) recommendations.

METHODS: From March to August 2009, all patients hospitalized in our hospital, for whom an IDC was requested, were prospectively enrolled. The adherence to recommendations was ascertained after 72 h from the IDC. The primary objective of the study was to evaluate the clinical cure rate 1 month after the IDC, according to the adherence to IDC recommendations.

RESULTS: An IDC was requested for 258 inpatients. The infectious disease (ID) was most often non-severe (66%), community-acquired (62%), and already under treatment (47%). IDC proposals were most often formulated via a formal consultation (57%). Physicians' adherence to IDC recommendations was 87% for diagnostic tests and 90% for antibiotherapy. In the multivariate analysis, severe infections and direct consultation were independently associated with increased odds of adherence to recommendations for performing diagnostic tests (odds ratios 5.4 and 4.0, respectively). The overall clinical cure rate was 84% and this did not differ according to the adherence to IDC recommendations for diagnostic tests (84.3 vs. 71.4%, p = 0.15) and antimicrobial treatment (84.8 vs. 77.8%, p = 0.34).

CONCLUSIONS: Some limitations of the study may explain the lack of evidence of a clinical benefit, such as the very high level of adherence to IDC recommendations and the low proportion of severe infections. However, clinical improvement was always better when recommendations were followed. Therefore, further larger randomized multicentric studies including more patients suffering from more severe IDs may be needed in order to demonstrate a clinical impact.}, } @article {pmid22718308, year = {2012}, author = {Vargas, AC and McCart Reed, AE and Waddell, N and Lane, A and Reid, LE and Smart, CE and Cocciardi, S and da Silva, L and Song, S and Chenevix-Trench, G and Simpson, PT and Lakhani, SR}, title = {Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression.}, journal = {Breast cancer research and treatment}, volume = {135}, number = {1}, pages = {153-165}, doi = {10.1007/s10549-012-2123-4}, pmid = {22718308}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Collagen Type V/biosynthesis/genetics ; Collagen Type XI/biosynthesis/genetics ; Disease Progression ; Epithelial Cells/*metabolism ; Extracellular Matrix/genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/biosynthesis/genetics ; Matrix Metalloproteinase 13/biosynthesis/genetics ; Membrane Proteins/biosynthesis/genetics ; Stromal Cells/*metabolism ; Tumor Microenvironment ; }, abstract = {The progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in the evolution of breast cancer. There is some evidence to suggest that dynamic interactions between the neoplastic cells and the tumour microenvironment play an important role. Using the whole-genome cDNA-mediated annealing, selection, extension and ligation assay (WG-DASL, Illumina), we performed gene expression profiling on 87 formalin-fixed paraffin-embedded (FFPE) samples from 17 patients consisting of matched IDC, DCIS and three types of stroma: IDC-S (<3 mm from IDC), DCIS-S (<3 mm from DCIS) and breast cancer associated-normal stroma (BC-NS; >10 mm from IDC or DCIS). Differential gene expression analysis was validated by quantitative real time-PCR, immunohistochemistry and immunofluorescence. The expression of several genes was down-regulated in stroma from cancer patients relative to normal stroma from reduction mammoplasties. In contrast, neoplastic epithelium underwent more gene expression changes during progression, including down regulation of SFRP1. In particular, we observed that molecules related to extracellular matrix (ECM) remodelling (e.g. COL11A1, COL5A2 and MMP13) were differentially expressed between DCIS and IDC. COL11A1 was overexpressed in IDC relative to DCIS and was expressed by both the epithelial and stromal compartments but was enriched in invading neoplastic epithelial cells. The contributions of both the epithelial and stromal compartments to the clinically important scenario of progression from DCIS to IDC. Gene expression profiles, we identified differential expression of genes related to ECM remodelling, and specifically the elevated expression of genes such as COL11A1, COL5A2 and MMP13 in epithelial cells of IDC. We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development.}, } @article {pmid22717250, year = {2012}, author = {Erdogan, D and Tayyar, S and Uysal, BA and Icli, A and Karabacak, M and Ozaydin, M and Dogan, A}, title = {Effects of allopurinol on coronary microvascular and left ventricular function in patients with idiopathic dilated cardiomyopathy.}, journal = {The Canadian journal of cardiology}, volume = {28}, number = {6}, pages = {721-727}, doi = {10.1016/j.cjca.2012.04.005}, pmid = {22717250}, issn = {1916-7075}, mesh = {Adult ; Aged ; Allopurinol/administration & dosage/*therapeutic use ; Biomarkers/blood ; Cardiomyopathy, Dilated/blood/*drug therapy/physiopathology ; Coronary Circulation/*drug effects ; Diastole ; Dose-Response Relationship, Drug ; Echocardiography ; Enzyme Inhibitors/administration & dosage/therapeutic use ; Female ; Heart Ventricles/diagnostic imaging/drug effects/*physiopathology ; Humans ; Male ; Middle Aged ; Stroke Volume/*drug effects ; Systole ; Treatment Outcome ; Uric Acid/blood ; Ventricular Function, Left/*drug effects ; Xanthine Oxidase/blood/drug effects ; }, abstract = {BACKGROUND: Uric acid (UA) is an independent marker of mortality and associated with increased oxidative stress in patients with congestive heart failure (CHF). The present study aimed to investigate the effect of allopurinol on left ventricular (LV) function and coronary microvascular integrity in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS: Thirty-nine consecutive IDC patients were divided into 2 groups: elevated (> 7 mg/dL for men and >6.5 mg/dL for women; n = 24) and normal (n = 15) UA. Allopurinol 300 mg per day was given to the elevated UA group. Patients with elevated UA were assessed after a 3-month treatment period. Echocardiography assessing coronary flow reserve (CFR) and systolic and diastolic LV functions were studied.

RESULTS: LV ejection fraction was significantly lower in elevated UA group: mean (interquartile range), 32.3% (26.0-36.5%) vs 37.3% (35.5-39.1%) (P < 0.01). Also, CFR and LV diastolic and combined function parameters were more prominently impaired in the elevated UA group. After allopurinol treatment, UA was significantly decreased (7.2 mg/dL [6.8-7.8] to 4.4 mg/dL [3.9-5.8]; P < 0.001) and CFR was markedly improved (1.87 [1.63-2.00] to 2.20 [1.87-2.49]; P < 0.001). The therapeutic effect of allopurinol on the reduction of UA from baseline was directly related to the improvement of CFR (r = 0.49; P = 0.01). Mitral A and E/E' were reduced, while S', E', E/A, and E'/A' were increased significantly.

CONCLUSIONS: The present study showed that 3-month treatment with allopurinol was significantly associated with reduced UA levels, and improvement of CFR and LV functions in patients with IDC and hyperuricemia.}, } @article {pmid22715888, year = {2012}, author = {Barbalaco Neto, G and Rossetti, C and Fonseca, FL and Valenti, VE and de Abreu, LC}, title = {Ductal carcinoma in situ in core needle biopsies and its association with extensive in situ component in the surgical specimen.}, journal = {International archives of medicine}, volume = {5}, number = {}, pages = {19}, pmid = {22715888}, issn = {1755-7682}, abstract = {BACKGROUND: We evaluated the presence of ductal carcinoma in situ (DCIS) in core needle biopsies (CNB) from invasive ductal lesions.

METHODS: Retrospective study, which analyzed 90 cases of invasive ductal carcinoma lesions. The percentage of DCIS was quantified in each specimens obtained from CNB, which were compared to the surgical specimens. CNB and surgical specimens were evaluated by the same pathologist, and the percentage of DCIS in CNB was evaluated (percentage) and divided into categories. We considered the following parameters regarding the amount of DCIS: 1 = 0; 2 = 1 for 5%; 3 = 6 for 24%; 4 = 25 for 50%; 5 = 51 for 75% and 6 = 76 for 99%. The number of fragments and the histological pattern of DCIS was found.

RESULTS: We found the following results regarding the distribution of the percentage of DCIS in the CNB: 1 = 63.3%; 2 = 12.2%; 3 = 12.2%; 4 = 5.6%; 5 = 1.1% and 6 = 5.6%. The logistic regression analysis showed that CNB percentages above 45% reflected the presence of DCIS in the surgical specimen in 100% of the cases (p < 0.001), with a specificity of 100%, accuracy of 83.3% and false positive rate of 0% (p <0.001).

CONCLUSION: There is direct relationship between extensive intraductal component in the surgical specimen when the core biopsy shows 45% or more of the DCI or microinvasive in the material examined.}, } @article {pmid22712893, year = {2012}, author = {Van Balkom, ID and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development, cognition, and behaviour in Pitt-Hopkins syndrome.}, journal = {Developmental medicine and child neurology}, volume = {54}, number = {10}, pages = {925-931}, doi = {10.1111/j.1469-8749.2012.04339.x}, pmid = {22712893}, issn = {1469-8749}, mesh = {Adolescent ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics ; Belgium ; Child ; Child Behavior Disorders/*diagnosis/genetics/*psychology ; Child Development Disorders, Pervasive/*diagnosis/genetics/*psychology ; Child, Preschool ; Cognition Disorders/*diagnosis/genetics/*psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Diagnosis, Differential ; Facies ; Female ; Humans ; Hyperventilation/*diagnosis/genetics/*psychology ; Intellectual Disability/*diagnosis/genetics/*psychology ; Language Development Disorders/diagnosis/genetics/psychology ; Male ; Netherlands ; Neuropsychological Tests ; Stereotypic Movement Disorder/diagnosis/genetics/psychology ; Transcription Factor 4 ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIM: The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt-Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).

METHOD: The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.

RESULTS: All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.

INTERPRETATION: Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.}, } @article {pmid22709451, year = {2012}, author = {Iusco, DR and Navarra, G and Bonomi, S and Grassi, A and Vicari, S and Virzì, S}, title = {Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report.}, journal = {Il Giornale di chirurgia}, volume = {33}, number = {5}, pages = {163-167}, pmid = {22709451}, issn = {0391-9005}, mesh = {Adenocarcinoma, Mucinous/surgery ; Carcinoma, Ductal ; *Cystadenoma, Mucinous ; Female ; Humans ; Pancreas ; *Pancreatectomy ; Pancreatic Neoplasms/surgery ; Pregnancy ; }, abstract = {BACKGROUND: Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy.

CASE REPORT: A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors.

CONCLUSIONS: To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.}, } @article {pmid22705704, year = {2012}, author = {Fujikawa, T and Mukai, K and Tanaka, A and Abe, T and Yoshimoto, Y and Tada, S and Maekawa, H and Shimoike, N and Tanaka, H and Kawashima, T and Yokota, T}, title = {[A long survival of a patient with poor performance status who suffered from advanced right breast cancer with multiple lung metastases controlled by trastuzumab as a key drug].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {6}, pages = {1009-1012}, pmid = {22705704}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autopsy ; Bone Neoplasms/drug therapy/secondary ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Fatal Outcome ; Female ; Humans ; Lung Neoplasms/*drug therapy/secondary ; Middle Aged ; Trastuzumab ; }, abstract = {We report a case of a 60-year-old woman with poor performance status (PS). She suffered from advanced right breast cancer with multiple lung metastases, which was controlled by chemotherapy with trastuzumab as the key drug. The patient presented with a 4 cm-sized large right breast mass. Her PS was poor due to progressive spinocerebellar degeneration. The biopsy specimen of the breast mass showed scirrhous type of the invasive ductal carcinoma (ER+, HER2 2+). Multiple lung metastases were also detected by computed tomography. Considering her poor PS, the patient was treated with mild systemic therapy using trastuzumab as the key drug. A different drug response was achieved between the breast mass and lung metastatic lesions, and the tumors were maintained as stable disease (SD) during first 18 months. However, she finally passed away due to respiratory failure resulting from lung metastasis, 33 months after starting treatment. The autopsy findings showed a difference of HER2 expression between the breast tumor and lung metastatic lesions. It must be recognized that differences of HER2 expression between the primary tumor and metastatic lesions are sometimes demonstrated in patients with breast cancer, and that trastuzumab can be used as a key drug in some patients as in the current case.}, } @article {pmid22705703, year = {2012}, author = {Sasaki, Y and Okuyama, M and Hibino, M and Tenma, K and Nakamura, M}, title = {[A case of elderly locally-advanced breast cancer with skin ulcer responding to letrozole].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {6}, pages = {1005-1008}, pmid = {22705703}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Breast Neoplasms/complications/*drug therapy/pathology ; Carcinoma, Ductal, Breast/complications/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Neoplasm Grading ; Neoplasm Staging ; Nitriles/*therapeutic use ; Skin Ulcer/*etiology ; Triazoles/*therapeutic use ; }, abstract = {We report an 84-year-old woman with an ulcerated tumor of her right breast. The histological examination showed invasive ductal carcinoma, ER (allred-score 8), PgR (allred-score 0), and HER2 (0). Computed tomography and bone scintigraphy showed no distant metastases. She was diagnosed with right locally advanced breast cancer (cT4bN2aM0, stageIIIB) and received hormone therapy with letrozole. One year after, the carcinoma was reduced in size and the skin ulcer had disappeared. Two years later, the carcinoma had grown back slightly, but the skin ulcer was still undetectable. Hormone therapy alone was considered useful for treatment of elderly locally advanced breast cancer patients.}, } @article {pmid22695443, year = {2012}, author = {Haider, AH and Villegas, CV and Saleem, T and Efron, DT and Stevens, KA and Oyetunji, TA and Cornwell, EE and Bowman, S and Haack, S and Baker, SP and Schneider, EB}, title = {Should the IDC-9 Trauma Mortality Prediction Model become the new paradigm for benchmarking trauma outcomes?.}, journal = {The journal of trauma and acute care surgery}, volume = {72}, number = {6}, pages = {1695-1701}, doi = {10.1097/TA.0b013e318256a010}, pmid = {22695443}, issn = {2163-0763}, support = {K23 GM093112/GM/NIGMS NIH HHS/United States ; CCR302486//PHS HHS/United States ; K23GM093112-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Benchmarking ; Cohort Studies ; Databases, Factual ; Female ; Hospital Mortality/*trends ; Humans ; International Classification of Diseases/*statistics & numerical data ; Male ; Middle Aged ; Models, Statistical ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; Trauma Severity Indices ; Treatment Outcome ; United States ; Wounds and Injuries/*classification/*mortality/therapy ; Young Adult ; }, abstract = {BACKGROUND: Optimum quantification of injury severity remains an imprecise science with a need for improvement. The accuracy of the criterion standard Injury Severity Score (ISS) worsens as a patient's injury severity increases, especially among patients with penetrating trauma. The objective of this study was to comprehensively compare the mortality prediction ability of three anatomic injury severity indices: the ISS, the New ISS (NISS), and the DRG International Classification of Diseases-9th Rev.-Trauma Mortality Prediction Model (TMPM-ICD-9), a recently developed contemporary injury assessment model.

METHODS: Retrospective analysis of patients in the National Trauma Data Bank from 2007 to 2008. The TMPM-ICD-9 values were computed and compared with the ISS and NISS for each patient using in-hospital mortality after trauma as the outcome measure. Discrimination and calibration were compared using the area under the receiver operator characteristic curve. Subgroup analysis was performed to compare each score across varying ranges of injury severity and across different types of injury.

RESULTS: A total of 533,898 patients were identified with a crude mortality rate of 4.7%. The ISS and NISS performed equally in the groups with minor (ISS, 1-8) and moderate (ISS, 9-15) injuries, regardless of the injury type. However, in the populations with severe (ISS, 16-24) and very severe (ISS, ≥ 25) injuries for all injury types, the NISS predicted mortality better than the ISS did. The TMPM-ICD-9 outperformed both the NISS and ISS almost consistently.

CONCLUSION: The NISS and TMPM-ICD-9 are both superior predictors of mortality as compared with the ISS. The immediate adoption of NISS for evaluating trauma outcomes using trauma registry data is recommended. The TMPM-ICD-9 may be an even better measure of human injury, and its use in administrative or nonregistry data is suggested. Further research on its attributes is recommended because it has the potential to become the basis for benchmarking trauma outcomes.

LEVEL OF EVIDENCE: Prognostic study, level III.}, } @article {pmid22693402, year = {2011}, author = {Sarkar, DK and Maji, A and Saha, S and Biswas, JK}, title = {Oncoplastic Breast Surgery - Our Experiences in the Breast Clinic, IPGME&R, Kolkata.}, journal = {Indian journal of surgical oncology}, volume = {2}, number = {2}, pages = {112-117}, pmid = {22693402}, issn = {0976-6952}, abstract = {Oncoplastic breast surgery is the fusion of oncological and surgical principles to gain successful breast tumour excision with good cosmesis. It is an widely accepted and popular method in the western world. However, the picture is different in India. The major issues here, like late detection and advanced tumours, poor socio-economic status overriding quality of life issue and shortage of dedicated oncoplastic surgeons result in a poor acceptance and practice of oncoplastic breast surgery. This article explores the use of various oncoplastic techniques in clinical practice and discusses future directions in this emerging field in an Indian perspective. In our institute (breast care unit, I.P.G.M.E&R,Kolkata), we performed a retrospective study over a period of five years (2005-2009). It included a sample size of 30 patients with diagnosed breast cancer or Phylloides Tumor (PT). The study focused on the indications, type of oncoplastic procedure used, cosmetic outcome (shape / volume replacement, ptosis correction & chest wall coverage), complications faced and response to subsequent therapy. The indications, for which oncoplastic techniques were applied, were DCIS (2), LCIS (1), IDC (19) and phylloides tumor (8). Of the 30 patients, RAT was used in 8, LDMF (of various types and volume) was used in 16, pedicled TRAM flap was used in 3 and reduction mastopexy in 3.The procedural indications of reconstruction were total glandular replacement by TRAM flap, mini-LDMF to fill volume loss after BCS or wide local excision, rotation advancement technique for reshaping / symmetry maintenance after BCS or wide local excision, LDMF for chest wall coverage after MRM and reduction mastopexy after wide local excision. From patient's point of view the outcome of surgery was highly satisfactory (score 3 or more) in 19 out of 30 patients (63.33%). LDMF was the most commonly used (16 out of 30) oncoplastic procedure with least complication rates (0 out of 16). 4 out of 30 patients had complications related to the procedure. Chest wall coverage after MRM still forms the main indication of oncoplastic surgery in this country.}, } @article {pmid22692290, year = {2012}, author = {Shah, RB and Zhou, M}, title = {Atypical cribriform lesions of the prostate: clinical significance, differential diagnosis and current concept of intraductal carcinoma of the prostate.}, journal = {Advances in anatomic pathology}, volume = {19}, number = {4}, pages = {270-278}, doi = {10.1097/PAP.0b013e31825c6c0e}, pmid = {22692290}, issn = {1533-4031}, mesh = {Biopsy, Needle ; Carcinoma, Ductal/pathology ; Colorectal Neoplasms/pathology ; Humans ; Male ; Prostate/*pathology ; Prostatic Intraepithelial Neoplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Serine Endopeptidases/genetics ; Urothelium/pathology ; }, abstract = {Atypical cribriform lesions of the prostate gland consist of cribriform and rarely solid proliferation of prostate glands populated with cytologically atypical cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P). IDC-P is almost always associated with clinically aggressive and high-volume prostate carcinoma. In contrast, cribriform HGPIN is a putative neoplastic precursor lesion, and recent data have questioned whether HGPIN on needle biopsy is associated with a significantly increased cancer risk in subsequent biopsies, and whether the diagnosis mandates rebiopsy within the first year after its diagnosis. As the result, the distinction between these 2 lesions has profound clinical implications, especially on needle biopsies. Since its original description, several studies have attempted to further refine histologic definition of IDC-P in the past decade. Even though presence of certain morphologic features (eg, pleomorphic nuclei or nuclei 6× the size of adjacent nuclei, intraluminal necrosis, and dense cribriform and solid architecture) are seen only in IDC-P, IDC-P may also exhibit "low-grade" morphologic features that overlap with cribriform HGPIN. Emerging molecular data on TMPRSS:ERG gene fusions further support the fact that these 2 lesions are biologically distinct. IDC-P is an uncommon finding in prostate biopsies; however, patients with IDC-P as sole findings without concomitant prostate carcinoma in biopsy are recommended for either definitive treatment or immediate repeat biopsy. This article summarizes the morphologic and molecular characteristics of IDC-P and cribriform HGPIN and an approach to work-up of atypical cribriform lesions in prostate needle biopsies.}, } @article {pmid22691433, year = {2012}, author = {Daenthanasanmak, A and Salguero, G and Borchers, S and Figueiredo, C and Jacobs, R and Sundarasetty, BS and Schneider, A and Schambach, A and Eiz-Vesper, B and Blasczyk, R and Weissinger, EM and Ganser, A and Stripecke, R}, title = {Integrase-defective lentiviral vectors encoding cytokines induce differentiation of human dendritic cells and stimulate multivalent immune responses in vitro and in vivo.}, journal = {Vaccine}, volume = {30}, number = {34}, pages = {5118-5131}, doi = {10.1016/j.vaccine.2012.05.063}, pmid = {22691433}, issn = {1873-2518}, mesh = {Animals ; Antigens, Viral/genetics/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology ; *Cell Differentiation ; Cell Survival ; Culture Media/metabolism ; Cytokines/genetics/*immunology/metabolism ; Cytomegalovirus/genetics/immunology ; Dendritic Cells/cytology/*immunology ; Epitopes/immunology ; Genetic Vectors/genetics/immunology/metabolism ; Humans ; Immunity, Cellular ; Immunization ; Immunophenotyping ; Integrases/genetics ; Killer Cells, Natural/immunology ; Lentivirus/genetics/*metabolism ; Lymphocyte Activation ; Mice ; Mice, Inbred NOD ; Monocytes/immunology ; Phosphoproteins/genetics/immunology/metabolism ; Transgenes ; Viral Matrix Proteins/genetics/immunology/metabolism ; Viral Proteins/genetics/immunology/metabolism ; }, abstract = {Integrase-defective lentiviral vectors (ID-LVs) show several hallmarks of conventional lentiviral vectors such as absence of cytotoxic effects and long-term expression in non-replicating target cells. The integration rate of ID-LVs into the genome of target cells is dramatically reduced, which enhances safety and opens perspectives for their use in vaccine development. ID-LVs have been shown to be effective vaccines in mouse models, but functional studies with human cells in vitro and in vivo are lacking. Here, we evaluated whether ID-LVs expressing combinations of cytokines (GM-CSF/IL-4 or GM-CSF/IFN-α) used to transduce human monocytes would result in functional "induced dendritic cells" (iDCs). Overnight transduction of monocytes with high titer ID-LVs generated highly viable (14 days) and immunophenotypically stable iDCs expressing GM-CSF/IL-4 ("SmartDCs") or GM-CSF/IFN-α ("SmyleDCs"). SmartDCs and SmyleDCs maintained in vitro continuously secreted the transgenic cytokines and showed up-regulation of several endogenously produced inflammatory cytokines (IFN-γ, IL-2, -5, -6, and -8). Both iDC types potently stimulated T cells in mixed lymphocyte reactions at levels comparable to conventional DCs (maintained with exogenous cytokines). A single in vitro stimulation of CD8(+) T cells with autologous SmartDCs or SmyleDCs pulsed with peptide pools of pp65 (a human cytomegalovirus antigen) resulted in high expansion of central memory and effector memory CTLs reactive against different pp65 epitopes. We further evaluated the effects of SmartDCs and SmyleDCs to expand anti-pp65 CTLs in vivo using immune deficient NOD/Rag1((-/-))/IL-2rγ((-/-)) (NRG) mice. NRG mice immunized subcutaneously with SmartDCs or SmyleDCs co-expressing the full-length pp65 were subsequently infused with autologous CD8(+) T cells. Both types of iDCs effectively stimulated human CTLs reactive against different pp65 antigenic determinants in vivo. Due to the simplicity of generation, robust viability and combined capacity to stimulate homeostatic, antigenic and multivalent responses, iDCs are promising vaccines to be explored in immunization of lymphopenic patients in the post-transplantation setting.}, } @article {pmid22686145, year = {2012}, author = {Nakash, O and Nagar, M and Shoshani, A and Zubida, H and Harper, RA}, title = {The effect of acculturation and discrimination on mental health symptoms and risk behaviors among adolescent migrants in Israel.}, journal = {Cultural diversity & ethnic minority psychology}, volume = {18}, number = {3}, pages = {228-238}, doi = {10.1037/a0027659}, pmid = {22686145}, issn = {1099-9809}, mesh = {*Acculturation ; Adolescent ; Adolescent Behavior/*ethnology/psychology ; Child ; *Discrimination, Psychological ; Female ; Humans ; Israel ; Jews ; Male ; Mental Health/*ethnology ; Prejudice ; Psychiatric Status Rating Scales ; Regression Analysis ; *Risk-Taking ; Self Concept ; Socioeconomic Factors ; Surveys and Questionnaires ; *Transients and Migrants/psychology ; Young Adult ; }, abstract = {This study examines the role of acculturation, perceived discrimination, and self-esteem in predicting the mental health symptoms and risk behaviors among 1.5 and second generation non-Jewish adolescents born to migrant families compared with native-born Jewish Israeli adolescents in Israel. Participants included n = 65 1.5 migrant adolescents, n = 60 second generation migrant adolescents, and n = 146 age, gender, and socioeconomic matched sample of native-born Jewish Israelis. Participants completed measures of acculturation pattern, perceived discrimination, and self-esteem as well as measures of mental health symptoms and risk behaviors. Results show that migrant adolescents across generations reported worse mental health symptoms compared with native-born Jewish Israelis. However, only the 1.5 generation migrants reported higher engagement in risk behaviors compared with second generation migrants and native-born Jewish Israelis. Our findings further showed that acculturation plays an important role in predicting the mental health status of migrant youth, with those characterized with integrated acculturative pattern reporting lower mental health symptoms compared with assimilated acculturation pattern. Importantly, contextual factors, such as higher perception of discrimination in the receiving culture as well as individual factors such as lower self-esteem and female gender were strongly associated with worse mental health symptoms. The findings manifest the complex relationship between contextual factors and individual level variables in the acculturative process of migrants as well as the importance of examining the effect of migration generation on mental health outcomes.}, } @article {pmid22673183, year = {2012}, author = {Kim, BG and Gao, MQ and Choi, YP and Kang, S and Park, HR and Kang, KS and Cho, NH}, title = {Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {3}, pages = {R88}, pmid = {22673183}, issn = {1465-542X}, mesh = {*Anoikis ; Antibodies, Blocking ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Caspase 3/metabolism ; Cell Adhesion Molecules/immunology/*metabolism ; Cell Communication ; Cell Line, Tumor ; Cell Survival ; Female ; Fibrosis ; Humans ; Integrin alpha3beta1/metabolism ; Integrin beta1/immunology ; Integrin beta4/immunology/*metabolism ; MCF-7 Cells ; Myofibroblasts/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Up-Regulation ; rac1 GTP-Binding Protein/metabolism ; }, abstract = {INTRODUCTION: Although development of anoikis-resistant myofibroblasts during tissue remodeling is known to be associated with tumor invasion, the mechanism by which myofibroblasts become resistant to anoikis is unknown. We previously demonstrated laminin-332 upregulation in the fibrosis around invasive ductal carcinoma (IDC). Because laminin-332 promotes cell survival through binding to integrins, we hypothesized that invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts by upregulating laminin-332 expression during tissue remodeling. Here, we demonstrate that invasive breast cancer cells induce laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype.

METHODS: Three types of fibroblasts were isolated from the tumor burden, the fibrosis, and normal tissue of patients with early stage IDC (less than 10 mm diameter), designated cancer-associated fibroblasts (CAFs), interface fibroblasts (InFs), and normal breast fibroblasts (NBFs), respectively. To investigate direct and indirect crosstalk with tumor cells, fibroblasts were co-cultured with invasive MDA-MB-231 or noninvasive MCF7 cells or in conditioned medium. Anoikis resistance of fibroblasts was measured by cell viability and caspase-3 activity after incubation on poly-HEMA coated plates for 72 hours. Involvement of laminin-332/integrin α3β1 or α6β4 signaling in anoikis resistance was confirmed by treatment with purified laminin-332 or blocking antibodies against laminin-332, integrin β1, or integrin β4.

RESULTS: MDA-MB-231 cells induced laminin-332 upregulation and integrin β4 neoexpression in fibroblasts, leading to anoikis resistance. InFs showed a higher endogenous level of laminin-332 than did CAFs and NBFs. After stimulation with MDA-MB-231-conditioned medium, laminin-332 expression of InFs was dramatically increased and maintained under anoikis conditions. Laminin-332 upregulation was also observed in CAFs and NBFs, but at a lower level than in InFs. Laminin-332 induced Akt (Ser473) phosphorylation by binding to integrin α3β1. Integrin β4 neoexpression induced laminin-332-independent Rac1 activation and promoted anoikis resistance in fibroblasts approximately twofold more effectively than did laminin-332, regardless of the type of fibroblast. In addition, integrin β4 expression suppressed fibroblast aggregation in conditions of anoikis.

CONCLUSION: Invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin β4 neoexpression. Interface fibroblasts appear to be the primary myofibroblasts that interact with invasive tumor cells during tissue remodeling.}, } @article {pmid22670156, year = {2012}, author = {Kao, L and Bulkin, Y and Fineberg, S and Montgomery, L and Koenigsberg, T}, title = {A case report: lobular carcinoma in situ in a male patient with subsequent invasive ductal carcinoma identified on screening breast MRI.}, journal = {Journal of Cancer}, volume = {3}, number = {}, pages = {226-230}, pmid = {22670156}, issn = {1837-9664}, abstract = {Lobular carcinoma in situ is a form of in situ neoplasia that develops within the terminal lobules of the breast. It is an extremely rare finding in males due to the lack of lobular development in the male breast. The authors herein report an unusual case of incidentally discovered lobular carcinoma in situ in a male patient with recurrent bilateral gynecomastia who was subsequently diagnosed with invasive ductal carcinoma of the left breast. The pathology of lobular carcinoma in situ in a male as well as screening MRI surveillance of male patients at high risk for breast cancer are discussed, emphasizing the importance of screening and imaging follow up in men who are at high risk for breast cancer.}, } @article {pmid22670111, year = {2012}, author = {Lee, G and Clemons, M and Cho, J and Czarnota, GJ and Dinniwell, R}, title = {Caught in the middle: case study of a brachial (sentry) lymph node recurrence after resection and locoregional breast radiotherapy.}, journal = {Current oncology (Toronto, Ont.)}, volume = {19}, number = {3}, pages = {e211-5}, pmid = {22670111}, issn = {1718-7729}, abstract = {To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema.}, } @article {pmid22668577, year = {2012}, author = {Izquierdo, F and Suárez-Vilela, D and Honrado, E}, title = {Perineurial cells in granular cell tumors and neoplasms with perineural invasion: an immunohistochemical study.}, journal = {The American Journal of dermatopathology}, volume = {34}, number = {8}, pages = {800-809}, doi = {10.1097/DAD.0b013e31824ba93b}, pmid = {22668577}, issn = {1533-0311}, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/analysis ; Child ; Female ; Granular Cell Tumor/metabolism/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Nerve Sheath Neoplasms/metabolism/pathology ; Peripheral Nerves/metabolism/*pathology ; Satellite Cells, Perineuronal/metabolism/*pathology ; Schwann Cells/pathology ; Young Adult ; }, abstract = {Granular cell tumors (GCT) are nerve sheath neoplasms composed of Schwann cells with granular cytoplasm. Perineurial cells are the cellular component of the perineurium and of perineuriomas, neoplasms supposedly derived from perineurial cells. However, perineurial cells have also been found in other Schwann cell-derived tumors. These cells have not been well studied in GCTs. We studied the presence of perineurial cells in a series of 24 GCTs with EMA, claudin-1, and Glut-1, which are immunohistochemical markers for perineurial cells. Three cases lacked nerve fascicles. Three cases showed no perineurial proliferation (grade 0), 7 showed grade 1 proliferation, and 11 showed grade 2 proliferation. For comparison, we studied 17 cases of neoplasms with perineural invasion (PNI): 7 cutaneous neoplasms [squamous cell carcinomas (n = 3), cutaneous lymphoma, malignant melanoma, eccrine carcinoma, congenital neurotropic nevus (n = 1 each)] and 10 noncutaneous tumors [prostatic (n = 2), gastric (n = 2), and colonic (n = 2) adenocarcinomas; invasive ductal carcinoma of breast (n = 2); urothelial carcinoma of bladder (n = 1); and oral squamous cell carcinoma (n = 1)] with the same antibodies for perineurial cells. We found perineurial cell proliferation in 10 cases, 6 grade 1, and 4 grade 2. These perineurial cells were limited to the areas around the nerve fascicles. Most of the tumor was devoid of perineurial cells. Thus, it was interpreted more as a hyperplastic or reactive phenomenon than a neoplastic component. Claudin-1 was the most sensitive of the 3 markers that we used. Such proliferation was less intense in non-GCTs. In conclusion, proliferation of perineurial cells in GCTs and neoplasms with PNI is a common finding that had not been previously studied. It seems to be a non-neoplastic phenomenon.}, } @article {pmid22662339, year = {2012}, author = {Iwatani, T and Kawabata, H and Miura, D and Inoshita, N and Ohta, Y}, title = {Nodular fasciitis of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {19}, number = {2}, pages = {180-182}, doi = {10.1007/s12282-009-0149-1}, pmid = {22662339}, issn = {1880-4233}, mesh = {Adult ; Breast Neoplasms/*pathology/surgery ; Fasciitis/*pathology/surgery ; Female ; Humans ; Nevus, Spindle Cell/*pathology/surgery ; Prognosis ; }, abstract = {Nodular fasciitis of the breast is a rare, benign, soft-tissue tumor that can clinically and radiologically mimic invasive ductal carcinoma. A 25-year-old woman presented with a palpable lesion in the lower inner aspect of the left breast. Radiologically, breast carcinoma could not be excluded. On examination of the core needle biopsy, the tumor was characterized histologically as a spindle cell tumor. Excisional biopsy was performed. The tumor was diagnosed as nodular fasciitis of the breast. The imaging and histological findings of this case are presented.}, } @article {pmid22662240, year = {2012}, author = {Vermeulen, JF and van de Ven, RA and Ercan, C and van der Groep, P and van der Wall, E and Bult, P and Christgen, M and Lehmann, U and Daniel, J and van Diest, PJ and Derksen, PW}, title = {Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e37864}, pmid = {22662240}, issn = {1932-6203}, mesh = {Adherens Junctions/metabolism ; Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/*pathology ; Cadherins/metabolism ; Carcinoma, Lobular/genetics/metabolism/*pathology ; Cell Line ; Cell Nucleus/*metabolism ; ErbB Receptors/metabolism ; Female ; Gene Expression ; Humans ; Mice ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Protein Transport ; Receptor, ErbB-2/deficiency ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Transcription Factors/genetics/*metabolism ; p120 GTPase Activating Protein/metabolism ; }, abstract = {Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.}, } @article {pmid22661137, year = {2012}, author = {Al-Rikabi, A and Husain, S}, title = {Increasing prevalence of breast cancer among Saudi patients attending a tertiary referral hospital: a retrospective epidemiologic study.}, journal = {Croatian medical journal}, volume = {53}, number = {3}, pages = {239-243}, pmid = {22661137}, issn = {1332-8166}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*epidemiology/pathology ; Epidemiologic Studies ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prevalence ; Registries ; Retrospective Studies ; Risk Assessment ; Saudi Arabia/epidemiology ; Young Adult ; }, abstract = {AIM: To determine the pattern of breast diseases among Saudi patients who underwent breast biopsy, with special emphasis on breast carcinoma.

METHODS: A retrospective review was made of all breast biopsy reports of a mass or lump from male and female patients seen between January 2001 and December 2010 at the King Khalid University Hospital, Riyadh, Saudi Arabia.

RESULTS: Of 1035 breast tissues reviewed, 939 specimens (90.7%) were from female patients. There were 690 benign (65.8%) and 345 (34.2%) malignant cases. In women, 603 (64.2%) specimens were benign and 336 (35.8%) were malignant. In men, 87 specimens (90.6%) were benign and 9 (9.4%) were malignant. All malignant cases from male patients belonged to invasive ductal carcinoma and the majority of malignant cases from female patients belonged to invasive/infiltrating ductal carcinoma. The proportion of malignancy was 18% in patients younger than 40 years and 63.2% in patients older than 60 years. The mean age of onset for malignancy was 48.6 years. The annual percentage incidence of malignant breast cancer steadily increased by 4.8%, from an annual rate of 23.5% in 2000 to 47.2% in 2007.

CONCLUSION: Among Saudi patients, there is a significant increase in the incidence of breast cancer, which occurs at an earlier age than in western countries. Continued vigilance, mammographic screening, and patient education are needed to establish early diagnosis and perform optimal treatment.}, } @article {pmid22655184, year = {2012}, author = {Costarelli, L and Campagna, D and Mauri, M and Fortunato, L}, title = {Intraductal proliferative lesions of the breast-terminology and biology matter: premalignant lesions or preinvasive cancer?.}, journal = {International journal of surgical oncology}, volume = {2012}, number = {}, pages = {501904}, pmid = {22655184}, issn = {2090-1410}, abstract = {Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspects of this disease probably necessitates further research to clarify if these entities can be identified as breast cancer precursors or as a malignant preinvasive disease. These issues are of great interest not only for their biological implications, but also to the clinician who must understand the disease and direct therapies. Molecular studies have shown that epitheliosis (usual ductal hyperplasia) is not monoclonal, while malignant lesions (atypical ductal hyperplasia, flat epithelial atypia, low-grade and high-grade intraductal carcinoma) constantly show these characteristics. These malignant lesions, classified with a DIN grading system (ductal intraepithelial neoplasia), are not obligate precursors of invasive ductal carcinoma and do not represent different evolving grades in a linear model of cancerogenesis. Breast cancerogenesis probably has different pathways with different morphologic precursors.}, } @article {pmid22647349, year = {2012}, author = {Tobin, NP and Lundgren, KL and Conway, C and Anagnostaki, L and Costello, S and Landberg, G}, title = {Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information.}, journal = {Human pathology}, volume = {43}, number = {11}, pages = {2053-2061}, doi = {10.1016/j.humpath.2012.02.015}, pmid = {22647349}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/mortality ; Carcinoma, Lobular/diagnosis/*metabolism/mortality ; Cell Nucleus/metabolism/pathology ; Cyclin D1/*metabolism ; Disease-Free Survival ; Female ; Gene Amplification ; Humans ; Image Processing, Computer-Assisted/*methods ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Survival Rate ; Sweden/epidemiology ; }, abstract = {The emergence of automated image analysis algorithms has aided the enumeration, quantification, and immunohistochemical analyses of tumor cells in both whole section and tissue microarray samples. To date, the focus of such algorithms in the breast cancer setting has been on traditional markers in the common invasive ductal carcinoma subtype. Here, we aimed to optimize and validate an automated analysis of the cell cycle regulator cyclin D1 in a large collection of invasive lobular carcinoma and relate its expression to clinicopathologic data. The image analysis algorithm was trained to optimally match manual scoring of cyclin D1 protein expression in a subset of invasive lobular carcinoma tissue microarray cores. The algorithm was capable of distinguishing cyclin D1-positive cells and illustrated high correlation with traditional manual scoring (κ=0.63). It was then applied to our entire cohort of 483 patients, with subsequent statistical comparisons to clinical data. We found no correlation between cyclin D1 expression and tumor size, grade, and lymph node status. However, overexpression of the protein was associated with reduced recurrence-free survival (P=.029), as was positive nodal status (P<.001) in patients with invasive lobular carcinoma. Finally, high cyclin D1 expression was associated with increased hazard ratio in multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89). In conclusion, we describe an image analysis algorithm capable of reliably analyzing cyclin D1 staining in invasive lobular carcinoma and have linked overexpression of the protein to increased recurrence risk. Our findings support the use of cyclin D1 as a clinically informative biomarker for invasive lobular breast cancer.}, } @article {pmid22642339, year = {2012}, author = {Halperin, E and Crisp, RJ and Husnu, S and Trzesniewski, KH and Dweck, CS and Gross, JJ}, title = {Promoting intergroup contact by changing beliefs: group malleability, intergroup anxiety, and contact motivation.}, journal = {Emotion (Washington, D.C.)}, volume = {12}, number = {6}, pages = {1192-1195}, doi = {10.1037/a0028620}, pmid = {22642339}, issn = {1931-1516}, mesh = {Adult ; Aged ; Anxiety/*psychology ; Attitude/*ethnology ; *Conflict, Psychological ; Cyprus/ethnology ; Female ; *Group Processes ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; Motivation/*physiology ; Psychological Tests ; Young Adult ; }, abstract = {Intergroup contact plays a crucial role in moderating long-term conflicts. Unfortunately, the motivation to make contact with outgroup members is usually very low in such conflicts. We hypothesized that one limiting factor is the belief that groups cannot change, which leads to increased intergroup anxiety and decreased contact motivation. To test this hypothesis, we experimentally manipulated beliefs about group malleability in the context of the conflict between Greek and Turkish Cypriots and then assessed intergroup anxiety and motivation to engage in intergroup contact. Turkish Cypriots who were led to believe that groups can change (with no mention of the specific groups involved) reported lower levels of intergroup anxiety and higher motivation to interact and communicate with Greek Cypriots in the future, compared with those who were led to believe that groups cannot change. This effect of group malleability manipulation on contact motivation was mediated by intergroup anxiety.}, } @article {pmid22641350, year = {2012}, author = {Cancemi, P and Di Cara, G and Albanese, NN and Costantini, F and Marabeti, MR and Musso, R and Riili, I and Lupo, C and Roz, E and Pucci-Minafra, I}, title = {Differential occurrence of S100A7 in breast cancer tissues: a proteomic-based investigation.}, journal = {Proteomics. Clinical applications}, volume = {6}, number = {7-8}, pages = {364-373}, doi = {10.1002/prca.201100072}, pmid = {22641350}, issn = {1862-8354}, mesh = {Amino Acid Sequence ; Breast Neoplasms/*metabolism/pathology ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Immunohistochemistry ; Molecular Sequence Data ; Neoplasm Proteins/chemistry/metabolism ; Protein Isoforms/chemistry/metabolism ; Proteomics/*methods ; Reproducibility of Results ; S100 Calcium Binding Protein A7 ; S100 Proteins/chemistry/*metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {PURPOSE: The present study reports for the first time a large-scale proteomic screening of the occurrence, subcellular localization and relative quantification of the S100A7 protein among a group of 100 patients, clinically grouped for the diagnosis of infiltrating ductal carcinoma (IDC).

EXPERIMENTAL DESIGN: To this purpose, the methods of differential proteomics, Western blotting, and immunohistochemistry were used.

RESULTS: The identity of two isoforms of the protein was assessed by mass spectrometry and immunologically confirmed. Moreover, we proved by immunocytochemical applications the exclusive localization of the protein within the neoplastic cells. The correlation of S100A7 expression levels with the collective profile of cancer patients' proteomics predicted functional interactions, distinct for the two isoforms. The S100A7b isoform was significantly correlated with specific protein clusters (calcium binding, signaling and cell motion, heat shock and folding) and intercrossing pathways (antioxidant, metabolic and apoptotic pathways), while the more acidic isoform was correlated with a narrow number of proteins mainly unrelated to the b isoform.

This study is the first proteomic-based report on S100A7 in a large series of IDC patients. The correlation with in silico data may significantly contribute the knowledge of possible pathways for S100A7, providing novel insights into the mechanism of action of this protein. We suggest that each S100A7 isoform is involved in critical phases of the breast cancer growth and progression, probably through interaction with different partner proteins.}, } @article {pmid22618481, year = {2012}, author = {Schmachtenberg, C and Engelken, F and Fischer, T and Bick, U and Poellinger, A and Fallenberg, EM}, title = {Intraoperative specimen radiography in patients with nonpalpable malignant breast lesions.}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {184}, number = {7}, pages = {635-642}, doi = {10.1055/s-0032-1312730}, pmid = {22618481}, issn = {1438-9010}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*surgery ; Female ; Humans ; Mastectomy/*methods ; Middle Aged ; Observer Variation ; Palpation ; Radiography ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Single-Blind Method ; Surgery, Computer-Assisted/*methods ; Treatment Outcome ; Young Adult ; }, abstract = {PURPOSE: Specimen mammography of nonpalpable wire-localized breast lesions is the standard in breast-conserving surgery. The aim of this study was to evaluate the reliability of intraoperative 2-view specimen mammography in different cancer types.

MATERIALS AND METHODS: After ethics approval, 3 readers retrospectively evaluated margins on 266 2-view specimen radiographs. They determined the closest margin and the orientation. The results were correlated with the histopathology (intra-class correlation coefficient [ICC] and contingency coefficient [CC]) and compared (Wilcoxon test).

RESULTS: Invasive ductal carcinoma (IDC) with ductal carcinoma in situ (DCIS) was present in 115 (43 %), IDC in 75 (28 %), invasive lobular carcinoma (ILC) in 57 (22 %) and rare cancers (CA) in 19 specimens (7 %). The sensitivity/specificity and positive/negative predictive value (P/NPV) of specimen mammography were 0.50/0.86 and 0.86/0.50 for CA, 0.42/0.68 and 0.48/0.63 for IDC, 0.36/0.81 and 0.69/0.51 for ILC, and 0.22/0.78 and 0.68/0.32 for IDC+DCIS. Readers correctly identified the orientation of the closest margin in at least one view in an average of 149 specimens (56 %). CCs were between 0.680 (IDC) and 0.912 (CA), suggesting a moderate correlation between radiographic and histological orientation. The correlations were worse for the radiographic and histological distances, with ICC ranging from 0.238 (ILC) to 0.475 (CA). The Wilcoxon test revealed overestimation of the radiographic margins compared to the histological ones for DCIS.

CONCLUSION: Our results suggest that specimen radiography has relatively good overall specificity and good PPV, while the sensitivity and NPV are low for DCIS. A negative result on specimen radiography does not rule out histologically involved margins.}, } @article {pmid22616572, year = {2012}, author = {Atalay, C and Irkkan, C}, title = {Predictive factors for residual disease in re-excision specimens after breast-conserving surgery.}, journal = {The breast journal}, volume = {18}, number = {4}, pages = {339-344}, doi = {10.1111/j.1524-4741.2012.01249.x}, pmid = {22616572}, issn = {1524-4741}, mesh = {Adult ; Axilla/pathology/surgery ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm, Residual/*pathology ; Pathology, Surgical/*methods ; Predictive Value of Tests ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; }, abstract = {Local recurrence is an issue of concern after breast-conserving therapy and removing the primary tumor with negative surgical margins is the most important determinant of local recurrence. However, some patients with positive margins after initial surgery will have no residual tumor in the re-excision specimen. To avoid unnecessary re-excisions, factors predicting residual disease in re-excision material should be determined. This study aimed to determine the predictive factors for residual disease in the re-excision material in a homogeneous group of patients with positive margins and only invasive ductal carcinoma. Breast cancer patients treated between 2005 and 2008 with breast-conserving surgery and subsequent re-excisions due to positive surgical margins after initial surgery were included in the study. Patients were divided into two groups as those with and without residual disease in the re-excision material. One hundred and four breast cancer patients were included in the study. Forty-seven patients (45.2%) had residual tumor in re-excision specimen. Patient characteristics such as age (p = 0.42) and physical findings (p = 1.0) and specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and progesterone (p = 0.37) receptor status, axillary lymph node metastases (p = 0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p = 0.064) were found as insignificant factors for predicting residual tumor. Large tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2) positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002) significantly increased the probability of finding residual disease after re-excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to specimen volume ratio of >70% (p = 0.006) independently predicted the presence of residual disease. As a result, in patients with HER2 positive tumors larger than 3 cm, larger volume of breast tissue around the tumor should be removed to decrease the number of re-excisions due to positive surgical margins.}, } @article {pmid22616038, year = {2012}, author = {Leddy, R and Irshad, A and Rumboldt, T and Cluver, A and Campbell, A and Ackerman, S}, title = {Review of metaplastic carcinoma of the breast: imaging findings and pathologic features.}, journal = {Journal of clinical imaging science}, volume = {2}, number = {}, pages = {21}, pmid = {22616038}, issn = {2156-5597}, abstract = {Metaplastic carcinoma (MPC), an uncommon but often aggressive breast cancer, can be challenging to differentiate from other types of breast cancer and even benign lesions based on the imaging appearance. It has a variable pathology classification system. These types of tumors are generally rapidly growing palpable masses. MPCs on imaging can present with imaging features similar to invasive ductal carcinoma and probably even benign lesions. The purpose of this article is to review MPC of the breast including the pathology subtypes, imaging features, and imaging pathology correlations. By understanding the clinical picture, pathology, and overlap in imaging characteristics of MPC with invasive ductal carcinoma and probably benign lesions can assist in diagnosing these difficult malignancies.}, } @article {pmid22612513, year = {2012}, author = {Deng, Y and Xue, D and Wang, X and Xu, S and Ao, Q and Hu, Z and Wang, G}, title = {Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype.}, journal = {Pathology international}, volume = {62}, number = {6}, pages = {429-432}, doi = {10.1111/j.1440-1827.2012.02810.x}, pmid = {22612513}, issn = {1440-1827}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Basal Cell/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Cystadenocarcinoma, Mucinous/metabolism/*secondary ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Mastectomy ; Neoplasm Staging ; Neoplasms, Multiple Primary ; }, abstract = {Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.}, } @article {pmid22611364, year = {2012}, author = {Okamoto, H and Kawaoi, A and Ogawara, T and Fujii, H}, title = {Invasive ductal carcinoma arising from an ectopic pancreas in the gastric wall: a long-term survival case.}, journal = {Case reports in oncology}, volume = {5}, number = {1}, pages = {69-73}, pmid = {22611364}, issn = {1662-6575}, abstract = {A case of invasive ductal carcinoma of an ectopic pancreas in the stomach in a 74-year-old woman is presented. A 4.0 cm gastric submucosal tumor (SMT) was resected surgically. Histologically, the tumor showed cystic tissue consisting of an ectopic pancreas with foci of a moderately differentiated tubular adenocarcinoma. In this tumor, small pancreatic tissues, acini, Langerhans islets, and ductular cells were detected in the gastric SMT. The patient has experienced long-term survival. The incidence of pancreatic cancer of an ectopic pancreas is rare, and the etiology of this disease is discussed in the literature.}, } @article {pmid22607447, year = {2012}, author = {Yamaguchi, R and Tsuchiya, S and Koshikawa, T and Yokoyama, T and Mibuchi, K and Nonaka, Y and Ito, S and Higuchi, H and Nagao, M and Higaki, K and Watanabe, J and Kage, M and Yano, H}, title = {Evaluation of inadequate, indeterminate, false-negative and false-positive cases in cytological examination for breast cancer according to histological type.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {53}, pmid = {22607447}, issn = {1746-1596}, mesh = {Adenocarcinoma, Scirrhous/pathology ; Biopsy, Needle ; Breast Neoplasms/classification/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Chi-Square Distribution ; *Cytological Techniques ; False Negative Reactions ; False Positive Reactions ; Female ; Fibroadenoma/pathology ; Fibrocystic Breast Disease/*pathology ; Humans ; Japan ; Papilloma/pathology ; Predictive Value of Tests ; }, abstract = {BACKGROUND: We previously investigated the current status of breast cytology cancer screening at seven institutes in our area of southern Fukuoka Prefecture, and found some differences in diagnostic accuracy among the institutions. In the present study, we evaluated the cases involved and noted possible reasons for their original cytological classification as inadequate, indeterminate, false-negative and false-positive according to histological type.

METHODS: We evaluated the histological findings in 5693 individuals who underwent cytological examination for breast cancer (including inadequate, indeterminate, false-negative and false-positive cases), to determine the most common histological types and/or features in these settings and the usefulness/limitations of cytological examination for the diagnosis of breast cancer.

RESULTS: Among 1152 cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in 24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being significantly more frequent (49.5%) than papillotubular growing type (Papi-tub) (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%) and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were three false-positive cases, with one each of fibroadenoma, epidermal cyst and papilloma.

CONCLUSIONS: The inadequate, indeterminate, false-negative and false-positive cases showed similar histological types, notably SIDC for malignant tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to pay particular attention to the collection and assessment of aspirates for these histological types of breast disease. In particular, several inadequate, indeterminate and false-negative cases with samples collected by aspiration were diagnosed as SIDC. These findings should encourage the use of needle biopsy rather than aspiration when this histological type is identified on imaging. Namely, good communication between clinicians and pathological staff, and triple assessment (i.e., clinical, pathological and radiological assessment), are important for accurate diagnosis of aspiration samples.

VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423.}, } @article {pmid22606601, year = {2012}, author = {Gunia, SR and Patel, MS and Mamounas, EP}, title = {Pathologic Complete Response of HER-2 Neu-Positive Invasive Ductal Carcinoma and Ductal Carcinoma In Situ following Neoadjuvant Chemotherapy plus Trastuzumab: A Case Report and Review of Literature.}, journal = {Case reports in surgery}, volume = {2012}, number = {}, pages = {454273}, pmid = {22606601}, issn = {2090-6919}, abstract = {Pathologic complete response (pCR) after NC has been consistently associated with improved outcomes. Residual DCIS after NC does not portray worse prognosis compared to complete eradication of all disease but has clinical implications regarding surgical management. We report a case of pCR of DCIS associated with invasive carcinoma in an HER-2 + tumor after NC plus trastuzumab despite persistence of malignant-appearing microcalcifications mammographically. A 41-year-old Caucasian female presented with a 4 × 4 cm mass in the right breast and a 2.5 cm right axillary node. Mammogram showed a 2.5 cm mass and a 12 cm area of linear pleomorphic, suspicious calcifications in the upper part of the breast. Core biopsy revealed invasive ductal carcinoma and DCIS associated with calcifications (ER 85%, PR 6%, Her2neu 3+ by IHC). Axillary node FNA was positive for malignancy. The patient received doxorubicin/cyclophosphamide (AC) → paclitaxel plus T with complete clinical and radiologic response but no significant change in the microcalcifications. Final pathology showed no residual invasive carcinoma or DCIS despite the presence of numerous ducts with microcalcifications. Documented eradication of DCIS has not been reported following NC when malignant-appearing calcifications persist and this observation may have important clinical implications regarding surgical management.}, } @article {pmid22586447, year = {2012}, author = {Huang, AJ and Yu, KD and Li, J and Fan, L and Shao, ZM}, title = {Polymorphism rs4919510:C>G in mature sequence of human microRNA-608 contributes to the risk of HER2-positive breast cancer but not other subtypes.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e35252}, pmid = {22586447}, issn = {1932-6203}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Case-Control Studies ; DNA-Binding Proteins/genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Heat Shock Transcription Factors ; Humans ; Logistic Models ; MicroRNAs/*genetics ; Middle Aged ; Neoplasms, Hormone-Dependent/*genetics/pathology ; Polymorphism, Genetic ; Receptor, ErbB-2/*genetics ; Risk Factors ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility.

METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism.

RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 × 10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA.

CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation.}, } @article {pmid22583197, year = {2012}, author = {Uddin, Z and Idrees, R and Aftab, K and Kayani, N}, title = {Invasive micropapillary carcinoma of breast: an under-recognized entity. a series of eight cases.}, journal = {The breast journal}, volume = {18}, number = {3}, pages = {267-271}, doi = {10.1111/j.1524-4741.2012.01232.x}, pmid = {22583197}, issn = {1524-4741}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Papillary/metabolism/*pathology/therapy ; Female ; Humans ; Immunohistochemistry/methods ; Lymph Nodes/pathology ; Middle Aged ; Mucin-1/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of breast is a morphologically distinct and relatively uncommon variant of invasive ductal carcinoma. It is characterized by small clusters of tumor cells with surrounding clear stromal spaces; a tendency for vascular permeation and therefore, an aggressive clinical course. This morphologic pattern can be easily missed especially in a small biopsy specimen because pathologists may disregard the clear spaces as artifactual. With a tendency of presenting at a higher stage, this morphological pattern needs to be mentioned in the histopathology report whenever it is encountered, either in its pure form or admixed with conventional ductal carcinoma. We describe eight cases of IMPC of breast along with their variable clinical presentations.}, } @article {pmid22581182, year = {2012}, author = {Jethon, A and Pula, B and Piotrowska, A and Wojnar, A and Rys, J and Dziegiel, P and Podhorska-Okolow, M}, title = {Angiotensin II type 1 receptor (AT-1R) expression correlates with VEGF-A and VEGF-D expression in invasive ductal breast cancer.}, journal = {Pathology oncology research : POR}, volume = {18}, number = {4}, pages = {867-873}, pmid = {22581182}, issn = {1532-2807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphangiogenesis ; Middle Aged ; Receptor, Angiotensin, Type 1/*biosynthesis/metabolism ; Statistics, Nonparametric ; Vascular Endothelial Growth Factor A/*biosynthesis/metabolism ; Vascular Endothelial Growth Factor D/*biosynthesis/metabolism ; }, abstract = {Recent studies point to the involvement of angiotensin II (Ang II) receptor type 1 (AT-1R) on processes of metastasing, stimulation of invasiveness and angiogenesis in tumours. In this study, the correlation between intensity of AT-1R expression and expression of lymph- and angiogenesis markers in invasive ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced AT-1R expression. Expression intensity of AT-1R was found to correlate with expressions of VEGF-A (r = 0.26; p = 0.008) and VEGF-D (r = 0.24; p = 0.015). Out of the examined markers of angiogenesis and lymphangiogenesis only the pronounced expression of VEGF-C was found to correlate with patient poor clinical outcome (p = 0.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could point to stimulatory action of Ang II on their expression what might result in augmented lymph- and angiogenesis in IDC.}, } @article {pmid22576064, year = {2012}, author = {Milgrom, S and Cody, H and Tan, L and Morrow, M and Pesce, C and Setton, J and Rogers, K and Arnold, B and Eaton, A and Catalano, J and McCormick, B and Powell, S and Ho, A}, title = {Characteristics and outcomes of sentinel node-positive breast cancer patients after total mastectomy without axillary-specific treatment.}, journal = {Annals of surgical oncology}, volume = {19}, number = {12}, pages = {3762-3770}, doi = {10.1245/s10434-012-2386-3}, pmid = {22576064}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/surgery ; Carcinoma, Lobular/*mortality/pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymph Node Excision ; Lymphatic Metastasis ; *Mastectomy, Simple ; Middle Aged ; Neoplasm Recurrence, Local/*mortality/pathology/surgery ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; }, abstract = {PURPOSE: Regional failure rates are low in patients with a positive sentinel lymph node biopsy (SLNB) who undergo breast-conserving therapy without axillary lymph node dissection (ALND). The applicability of these findings to total mastectomy (TM) patients is not established. Our aims were to evaluate the characteristics and outcomes of SLNB-positive TM patients who did not receive axillary-specific treatment and to compare them to similar patients who underwent breast-conserving surgery (BCS).

METHODS: A total of 535 patients with early-stage breast cancer who underwent definitive breast surgery (210 TM, 325 BCS), had a positive SLNB and did not receive ALND between 1997 and 2009 were identified from an institutional database. Characteristics and outcomes were compared between the TM and BCS groups.

RESULTS: Most patients had stage I to IIA, estrogen receptor-positive, progesterone receptor-positive, Her2-negative invasive ductal carcinoma, with minimal nodal disease. Compared to the BCS group, TM patients were younger, had larger tumors, had higher nomogram scores predicting additional axillary disease and were more likely to receive chemotherapy. Ninety-four percent of the BCS cohort and 5 % of the TM cohort received adjuvant radiotherapy. At a median follow-up of 57.8 months, the 4-year local, regional and distant failure rates were 1.7, 1.2 and 0.7 % in the TM group and 1.4, 1.0 and 3.7 % in the BCS group. The 4-year disease-free and overall survival rates were 94.8 and 97.8 % in the TM group and 90.1 and 92.6 % in the BCS group.

CONCLUSIONS: Early-stage breast cancer patients with minimal sentinel node disease experience excellent outcomes without ALND, whether they undergo BCS or TM.}, } @article {pmid22570516, year = {2012}, author = {Ragunath, PK and Reddy, BV and Abhinand, PA and Ahmed, SS}, title = {Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.}, journal = {Bioinformation}, volume = {8}, number = {8}, pages = {359-364}, pmid = {22570516}, issn = {0973-2063}, abstract = {Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to develop a differential diagnostic protocol to classify the two conditions. The main goal of the study is to construct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences, in order to explore the potential significant gene regulatory networks that can differentiate IDC and ILC and thereby understand the complex interactions that are influenced by the genetic networks. Out of the 54676 genes present on the GPL570 platform- 29 genes exhibited 4 fold up regulation in case of IDC and 22 in the case of ILC. The ductal and lobular tumors displayed a striking difference in the expression of genes associated with cell adhesion, protein folding, and protein phosphorylation and invasion. Construction of separate gene regulation networks for IDC and ILC on the basis of gene expression altercation can be utilized in understanding the distinction in the possible mechanism that underlies the pathological differences between the two, which can be exploited in identifying diagnostic or therapeutic targets.}, } @article {pmid22569827, year = {2012}, author = {Ebata, A and Suzuki, T and Takagi, K and Miki, Y and Onodera, Y and Nakamura, Y and Fujishima, F and Ishida, K and Watanabe, M and Tamaki, K and Ishida, T and Ohuchi, N and Sasano, H}, title = {Oestrogen-induced genes in ductal carcinoma in situ: their comparison with invasive ductal carcinoma.}, journal = {Endocrine-related cancer}, volume = {19}, number = {4}, pages = {485-496}, doi = {10.1530/ERC-11-0345}, pmid = {22569827}, issn = {1479-6821}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism ; Estrogens/*pharmacology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, Neoplasm/drug effects ; Humans ; Microarray Analysis ; Middle Aged ; Up-Regulation/drug effects/genetics ; }, abstract = {It is well known that oestrogens play important roles in both the pathogenesis and development of invasive ductal carcinoma (IDC) of human breast. However, molecular features of oestrogen actions have remained largely unclear in pure ductal carcinoma in situ (pDCIS), regarded as a precursor lesion of many IDCs. This is partly due to the fact that gene expression profiles of oestrogen-responsive genes have not been examined in pDCIS. Therefore, we first examined the profiles of oestrogen-induced genes in oestrogen receptor (ER)-positive pDCIS and DCIS (DCIS component (DCIS-c)) and IDC (IDC component (IDC-c)) components of IDC cases (n=4 respectively) by microarray analysis. Oestrogen-induced genes identified in this study were tentatively classified into three different groups in the hierarchical clustering analysis, and 33% of the genes were predominantly expressed in pDCIS rather than DCIS-c or IDC-c cases. Among these genes, the status of MYB (C-MYB), RBBP7 (RBAP46) and BIRC5 (survivin) expressions in carcinoma cells was significantly higher in ER-positive pDCIS (n=53) than that in ER-positive DCIS-c (n=27) or IDC-c (n=27) by subsequent immunohistochemical analysis of the corresponding genes (P<0.0001, P=0.03 and P=0.0003 respectively). In particular, the status of C-MYB immunoreactivity was inversely (P=0.006) correlated with Ki67 in the pDCIS cases. These results suggest that expression profiles of oestrogen-induced genes in pDCIS may be different from those in IDC; and C-MYB, RBAP46 and survivin may play important roles particularly among oestrogen-induced genes in ER-positive pDCIS.}, } @article {pmid22566709, year = {2013}, author = {Nakash, O and Levav, I and Gal, G}, title = {Common mental disorders in immigrant and second-generation respondents: results from the Israel-based World Mental Health Survey.}, journal = {The International journal of social psychiatry}, volume = {59}, number = {5}, pages = {508-515}, doi = {10.1177/0020764012443754}, pmid = {22566709}, issn = {1741-2854}, support = {R01 MH070884/MH/NIMH NIH HHS/United States ; R01-MH069864/MH/NIMH NIH HHS/United States ; R03-TW006481/TW/FIC NIH HHS/United States ; R13-MH066849/MH/NIMH NIH HHS/United States ; }, mesh = {Cohort Effect ; Confounding Factors, Epidemiologic ; Demography ; *Emigrants and Immigrants/psychology/statistics & numerical data ; Ethnicity/psychology ; Female ; Health Status Disparities ; Humans ; Interview, Psychological/methods ; Israel/ethnology ; *Life Change Events ; Male ; *Mental Disorders/diagnosis/epidemiology ; Mental Health/statistics & numerical data ; Prevalence ; *Social Environment ; Socioeconomic Factors ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The contrasting social status of ethnic groups differentially impacts the mental health of their members. This may be the case in Israel despite its egalitarian ideology. However, studies are a few and limited in scope.

AIM: To study mental health disparities between immigrant and second-generation disadvantaged and advantaged Jewish groups.

METHODS: Data were extracted from the Israel World Mental Health Survey. This included the Composite International Diagnostic Interview and the General Health Questionnaire. We compared 547 first-generation immigrants born in North Africa/Asia and 708 born in Europe/America; and 707 second-generation immigrants of North African/Asian origin and 449 of European/American origin.

RESULTS: The prevalence rate of common mental disorders in the preceding year was approximately double for respondents of North African/Asian origin compared with their European/American counterparts following adjustment for socio-demographic confounders. Inmigrants: North African/Asian 12.4%, SE = 1.5; European/American 6.4%, SE = 1.0 (AOR = 2.1, 95% CI 1.4-3.4). Second generation: North African/Asian 10.1%, SE = 1.2; European/American 5.4%, SE = 1.1 (AOR = 1.7, 95% CI 1.1-3.2). Significant differences in emotional distress mean scores were observed only among second-generation respondents: North African/Asian respondents reported higher emotional distress (M = 18.7, SE = 0.5) compared with European/American (M = 17.3, SE = 0.4) (Wald F = 13.31, p < .001).

CONCLUSIONS: Results showed disparities in the mental health measures in both generations. It is likely that social causation factors, such as restricted opportunities in the context of higher aspirations, partially account for the findings.}, } @article {pmid22564658, year = {2012}, author = {Kobayashi, T and Sato, Y and Hirukawa, H and Soeno, M and Shimoda, T and Matsuoka, H and Kobayashi, Y and Tada, T and Hatakeyama, K}, title = {Total pancreatectomy combined with partial pancreas autotransplantation for recurrent pancreatic cancer: a case report.}, journal = {Transplantation proceedings}, volume = {44}, number = {4}, pages = {1176-1179}, doi = {10.1016/j.transproceed.2012.03.016}, pmid = {22564658}, issn = {1873-2623}, mesh = {Blood Glucose/metabolism ; C-Peptide/blood ; CA-19-9 Antigen/blood ; Carcinoma, Pancreatic Ductal/diagnostic imaging/pathology/*surgery ; Female ; Glycated Hemoglobin/metabolism ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasm Recurrence, Local ; Neoplasm Staging ; *Pancreas Transplantation ; *Pancreatectomy ; Pancreatic Function Tests ; Pancreatic Neoplasms/diagnostic imaging/pathology/*surgery ; *Pancreaticoduodenectomy ; Reoperation ; Time Factors ; Tomography, X-Ray Computed ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {We describe a patient presenting with a resectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreatic head. We also performed a distal pancreas autotransplantation using a part of the resected pancreas to preserve endocrine function. Final histologic findings showed the second tumor to be an invasive ductal carcinoma consisting of a well-differentiated tubular adenocarcinoma with similar histopathologic findings as the first tumor. There were no microscopic lymph node metastases and no evidence of microvascular invasion (pStage IA [pT1, pN0, M0] and R0 according to the International Union Against Cancer TNM classification). The patient was discharged at 20 days after surgery without any trouble and followed by adjuvant chemotherapy with S-1. The carbohydrate antigen 19-9 value was again normalized after the second surgery. Twenty months after the second operation, the patient is alive without cancer recurrence. The pancreas graft is functioning with a blood glucose of 108 mg/dL, HbA1C of 6.2%, and serum C-peptide of 1.4 ng/mL.}, } @article {pmid22562585, year = {2012}, author = {Nakash, O and Nagar, M and Mandel, R and Alon, S and Gottfried, M and Levav, I}, title = {Ethnic differentials in mental health needs and service utilization among persons with cancer.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {20}, number = {9}, pages = {2217-2221}, pmid = {22562585}, issn = {1433-7339}, mesh = {Adult ; Arabs/psychology ; Female ; Hospitals, Public ; Humans ; Israel ; Jews/psychology ; Male ; Medical Audit ; Mental Health Services/*statistics & numerical data ; Middle Aged ; *Needs Assessment ; Neoplasms/*ethnology/*psychology ; Retrospective Studies ; }, abstract = {PURPOSE: Improving the assessment of and access to appropriate care for mental health problems among persons with cancer is essential, particularly for population groups that are at high risk for psychopathology. This study characterized ethnic differentials regarding needs and service utilization by Jewish (n = 1,430) and Arab-Israeli (n = 141) persons with cancer.

METHODS: We reviewed 284 randomly selected active medical charts in an oncology clinic in a large public hospital (November 2010-April 2011).

RESULTS: While 12% of the charts of the Jewish-Israeli sample included a record of psychiatric disorders or symptoms, only 5% of the charts of the Arab-Israeli sample had a similar record (χ² = 4.4, p < .05). Similarly, in a higher percentage of the charts of the Jewish-Israeli sample, the current utilization of psychotropics (18.2 and 5.6%, respectively; χ² = 6.7; p < .01) and/or psychotherapy (7.8 and 1.4%, respectively; χ² = 3.6; p < .05) was noted compared with the Arab-Israeli sample. Also, in a higher percentage of the charts of the Jewish-Israeli patients, a referral for psychotherapy was recorded compared with their Arab counterparts (9.1 and 4.3% respectively; χ² = 6.3; p < .05). In contrast, 19.1% of the Arab-Israelis were recommended with welfare assistance compared to their Jewish-Israeli counterparts, 10.5% (χ² = 5.35; p < .05).

CONCLUSIONS: Despite methodological limitations, findings confirm past research showing that disadvantaged ethnic minorities may receive differential recommendations for mental health problems among persons with cancer. This may contribute to the differential treatment gap in mental health care among persons with cancer of contrasting ethnic groups.}, } @article {pmid22562451, year = {2012}, author = {Yamamoto, Y and Shimada, K and Takeuchi, Y and Sofue, K and Shibamoto, K and Nara, S and Esaki, M and Sakamoto, Y and Kosuge, T and Hiraoka, N}, title = {Assessment of the interface between retroperitoneal fat infiltration of pancreatic ductal carcinoma and the major artery by multidetector-row computed tomography: surgical outcomes and correlation with histopathological extension.}, journal = {World journal of surgery}, volume = {36}, number = {9}, pages = {2192-2201}, pmid = {22562451}, issn = {1432-2323}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/*diagnostic imaging/pathology/surgery ; Female ; Hepatic Artery/*diagnostic imaging ; Humans ; Intra-Abdominal Fat/*diagnostic imaging/pathology ; Male ; Mesenteric Arteries/*diagnostic imaging ; Mesenteric Veins/diagnostic imaging ; Middle Aged ; *Multidetector Computed Tomography ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*diagnostic imaging/pathology/surgery ; Pancreaticoduodenectomy ; Portal Vein/diagnostic imaging ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Vascular Neoplasms/*diagnostic imaging/secondary/surgery ; }, abstract = {BACKGROUND: Precise assessment of retroperitoneal invasion is clinically important to allow the achievement of negative margin resections.

METHODS: The clinical records of 132 patients who underwent macroscopic curative pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinicopathological factors, including retroperitoneal fat infiltration classified into four groups by multidetector-row computed tomography (MDCT), were analyzed. The relationship between the grade of retroperitoneal fat infiltration and surgical outcomes, as well as various histopathological factors, was also investigated.

RESULTS: The 5 year survival rate was 55.6 % for grade 0 infiltration (n = 8), 38.7 % for grade 1 (n = 54), 16.4 % for grade 2 (n = 49), and 0 % for grade 3 (n = 21). There were significant differences in survival in each group. Extrapancreatic nerve invasion and the surgical margin status were significantly associated with retroperitoneal fat infiltration demonstrated on MDCT. According to the grading classification among the 43 patients with pathological portal vein invasion, the 5 year survival rate was 45.9 % for patients with grade 1, which was significantly better survival that those with grade 2 (P = 0.007).

CONCLUSION: The grading criteria for retroperitoneal fat infiltration may be useful as a predictor of survival after pancreaticoduodenectomy for pancreatic head carcinoma. Pancreaticoduodenectomy with portal vein resection could provide favorable survival in patients with grade 1 retroperitoneal fat infiltration, even if histopathological portal vein invasion is present.}, } @article {pmid22558599, year = {2011}, author = {Singhai, R and Patil, VW and Jaiswal, SR and Patil, SD and Tayade, MB and Patil, AV}, title = {E-Cadherin as a diagnostic biomarker in breast cancer.}, journal = {North American journal of medical sciences}, volume = {3}, number = {5}, pages = {227-233}, pmid = {22558599}, issn = {1947-2714}, abstract = {BACKGROUND: E-cadherin is expressed in most normal epithelial tissues. Selective loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas, leading E-cadherin to be classified as a tumor suppressor. Loss of E-cadherin has been demonstrated in invasive lobular carcinoma of the breast, but the relationship between E-cadherin expression and breast cancer histopathology and prognosis is less clear.

AIM: Our objective was to assess loss of E-cadherin as a diagnostic breast cancer biomarker and as an aid to the sub-classification of invasive breast cancer. We also correlated the loss of expression of E-cadherin with various clinical and pathologic prognostic factors.

MATERIAL AND METHODS: Breast cancer specimens after modified radical mastectomy were obtained from women who underwent surgery at Grant Medical College and Sir J.J Group of Hospitals, Mumbai, India between May 2007 and October 2010. We stained 276 breast cancers specimens with monoclonal antibodies to E-cadherin. The breast cancers were classified by histopathological type.

RESULTS: A statistical correlation of E-cadherin loss with a positive diagnosis of invasive lobular carcinoma was found, but there was no correlation with any prognostic tumor variables. A negative E-cadherin stain was a sensitive and specific biomarker to confirm the diagnosis of invasive lobular carcinoma (specificity 97.7%; negative predictive value 96.8%; sensitivity 88.1%; and positive predictive value 91.2%). Positive E-cadherin expression was also associated with tubulolobular carcinomas.

CONCLUSIONS: E-cadherin immunohistochemistry is helpful in classifying breast cancer cases with indeterminate histopathologic features. E-cadherin loss is uncommon in non-lobular carcinomas but shows no correlation to currently established prognostic variables.}, } @article {pmid22553811, year = {2012}, author = {Lin, X and Zhu, B and Finkelstein, SD and Saad, RS and Snitchler, A and Silverman, JF}, title = {Significance of loss of heterozygosity in predicting axillary lymph node metastasis of invasive ductal carcinoma of the breast.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {20}, number = {2}, pages = {116-123}, doi = {10.1097/pai.0b013e31822afce2}, pmid = {22553811}, issn = {1533-4058}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal/*genetics/*pathology ; Chromosomes, Human/*genetics ; DNA, Neoplasm/*genetics ; Female ; Humans ; *Loss of Heterozygosity ; Lymphatic Metastasis ; Middle Aged ; }, abstract = {Invasive ductal carcinoma (IDC) of breast metastatic to axillary lymph node (ALN) is a critical factor in determining stage and is a strong predictor of disease prognosis and survival. We studied ALN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications. Fourteen patients with IDC with positive ALN and 19 with negative ALN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was carried out in DNA isolated from primary tumors and metastatic tumors. ALN metastasis correlated with fractional mutation rate of primary and ALN metastatic tumors, primary tumor size, and nuclear grade, and did not correlate with expression of estrogen receptor, progesterone receptor, and Her2/neu. Loss of heterozygosity (LOH) detected at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22, and 22q13 may play an important role in the development and aggressiveness of IDC, and LOHs at 1p34-36, 17p13, and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that IDC develops through various pathways that have unique and personalized patterns of mutational changes, although they share similar morphology. Detection of LOH in IDC is not only useful in studying oncogenesis, but also predicting aggressiveness and ALN metastasis.}, } @article {pmid22553225, year = {2012}, author = {Stivalet, A and Luciani, A and Pigneur, F and Dao, TH and Beaussart, P and Merabet, Z and Perlbarg, J and Meyblum, E and Baranes, L and Calitchi, E and Lepage, C and Belkacemi, Y and Lagrange, JL and Lantieri, L and Rahmouni, A}, title = {Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {53}, number = {4}, pages = {367-375}, doi = {10.1258/ar.2012.110477}, pmid = {22553225}, issn = {1600-0455}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Lobular/drug therapy/*pathology/surgery ; Combined Modality Therapy ; Contrast Media ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Mammaplasty ; Mammography ; Mastectomy, Simple ; Meglumine ; Middle Aged ; Neoplasm Invasiveness ; Organometallic Compounds ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard.

PURPOSE: To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard.

MATERIAL AND METHODS: Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test).

RESULTS: Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile.

CONCLUSION: Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR-guided biopsy is required in case of suspicious MRI images in this context.}, } @article {pmid22551542, year = {2012}, author = {Rodríguez Pérez, A and Samper Ots, PM and López Carrizosa, MC and Pérez-Regadera Gómez, JF and Zapatero Ortuño, J and Sáez Garrido, Jde D and Martín de Miguel, MJ}, title = {Early-stage breast cancer conservative treatment: high-dose-rate brachytherapy boost in a single fraction of 700 cGy to the tumour bed.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {14}, number = {5}, pages = {362-368}, pmid = {22551542}, issn = {1699-3055}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/pathology/*radiotherapy ; Carcinoma, Lobular/pathology/*radiotherapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology/*radiotherapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND AND PURPOSE: Conservative treatment represents the current therapy for early-stage breast cancer. When risk factors for local relapse exist, a tumour bed boost is required. Retrospectively, we evaluated the prognostic factors influencing local recurrence (LR), overall survival (OS) and disease-free survival (DFS).

MATERIAL AND METHODS: After conservative treatment, 210 patients received a single-dose HDR brachytherapy (HDRBT) boost between June 1996 and December 2005. Mean age was 57 years; 75% had invasive ductal carcinoma. The most frequent surgery was lumpectomy (55.7%); 39.4% were G3, 18.6% intraductal component >25% and only 22% had negative margins.

RESULTS: With a mean follow-up of 85 months, at 5 and 10 years the OS was 93% and 88%, DFS 92% and 89%, and LR 3.6% and 5.3%, respectively. For LR, the risk factors were carcinoma in situ, N+ and involved margins, whereas for metastasis, the risk factors were T2 tumours, stage III, N+ and the presence of local recurrence.

CONCLUSIONS: HDR-BT boost in one fraction is an effective, simple and safe method for reducing LR. The outpatient setting and shorter treatment duration represent undeniable advantages.}, } @article {pmid22543207, year = {2012}, author = {Li, B and Chen, M and Nori, D and Chao, KS and Chen, AM and Chen, SL}, title = {Adjuvant radiation therapy and survival for pure tubular breast carcinoma--experience from the SEER database.}, journal = {International journal of radiation oncology, biology, physics}, volume = {84}, number = {1}, pages = {23-29}, doi = {10.1016/j.ijrobp.2011.10.063}, pmid = {22543207}, issn = {1879-355X}, mesh = {Adenocarcinoma/mortality/*radiotherapy/surgery ; Age Factors ; Aged ; Analysis of Variance ; Breast Neoplasms/mortality/*radiotherapy/surgery ; Breast Neoplasms, Male/mortality/radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/*radiotherapy/surgery ; Female ; Humans ; Male ; Mastectomy, Segmental/mortality/statistics & numerical data ; Middle Aged ; *Radiotherapy, Adjuvant/mortality ; Rare Diseases/mortality/*radiotherapy/surgery ; SEER Program ; Survival Analysis ; }, abstract = {PURPOSE: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement.

METHODS AND MATERIALS: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65.

RESULTS: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age ≤ 65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only).

CONCLUSIONS: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is important. Adjuvant radiation can be omitted for patients older than 65.}, } @article {pmid22543203, year = {2012}, author = {Nguyen, BT and Deb, S and Fox, S and Hill, P and Collins, M and Chua, BH}, title = {A prospective pathologic study to define the clinical target volume for partial breast radiation therapy in women with early breast cancer.}, journal = {International journal of radiation oncology, biology, physics}, volume = {84}, number = {5}, pages = {1116-1122}, doi = {10.1016/j.ijrobp.2012.02.038}, pmid = {22543203}, issn = {1879-355X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/chemistry/pathology/radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/pathology/radiotherapy/surgery ; Carcinoma, Lobular/chemistry/pathology/radiotherapy ; Female ; Humans ; Mastectomy/methods ; Middle Aged ; Neoplasm, Residual ; Prospective Studies ; Reoperation ; Sample Size ; Tumor Burden ; }, abstract = {PURPOSE: To determine an appropriate clinical target volume for partial breast radiation therapy (PBRT) based on the spatial distribution of residual invasive and in situ carcinoma after wide local excision (WLE) for early breast cancer or ductal carcinoma in situ (DCIS).

METHODS AND MATERIALS: We performed a prospective pathologic study of women potentially eligible for PBRT who had re-excision and/or completion mastectomy after WLE for early breast cancer or DCIS. A pathologic assessment protocol was used to determine the maximum radial extension (MRE) of residual carcinoma from the margin of the initial surgical cavity. Women were stratified by the closest initial radial margin width: negative (>1 mm), close (>0 mm and ≤ 1 mm), or involved.

RESULTS: The study population was composed of 133 women with a median age of 59 years (range, 27-82 years) and the following stage groups: 0 (13.5%), I (40.6%), II (38.3%), and III (7.5%). The histologic subtypes of the primary tumor were invasive ductal carcinoma (74.4%), invasive lobular carcinoma (12.0%), and DCIS alone (13.5%). Residual carcinoma was present in the re-excision and completion mastectomy specimens in 55.4%, 14.3%, and 7.2% of women with an involved, close, and negative margin, respectively. In the 77 women with a noninvolved radial margin, the MRE of residual disease, if present, was ≤ 10 mm in 97.4% (95% confidence interval 91.6-99.5) of cases. Larger MRE measurements were significantly associated with an involved margin (P<.001), tumor size >30 mm (P=.03), premenopausal status (P=.03), and negative progesterone receptor status (P=.05).

CONCLUSIONS: A clinical target volume margin of 10 mm would encompass microscopic residual disease in >90% of women potentially eligible for PBRT after WLE with noninvolved resection margins.}, } @article {pmid22539628, year = {2013}, author = {Nakash, O and Barchana, M and Liphshitz, I and Keinan-Boker, L and Levav, I}, title = {The effect of cancer on suicide in ethnic groups with a differential suicide risk.}, journal = {European journal of public health}, volume = {23}, number = {1}, pages = {114-115}, doi = {10.1093/eurpub/cks045}, pmid = {22539628}, issn = {1464-360X}, mesh = {Adult ; Age Distribution ; Aged ; Asian People/psychology/statistics & numerical data ; Black People/psychology/statistics & numerical data ; Confidence Intervals ; Ethnicity/psychology/*statistics & numerical data ; Female ; Humans ; Incidence ; Israel/ethnology ; Male ; Middle Aged ; Neoplasms/ethnology/*psychology ; Population Surveillance ; Registries ; Risk Factors ; Self-Injurious Behavior/ethnology/*psychology ; Sex Distribution ; Socioeconomic Factors ; Suicide/*ethnology/*psychology ; White People/psychology/statistics & numerical data ; }, abstract = {This study examined the suicide risk among persons with cancer in ethnic groups with differential suicide mortality in the general population. We calculated the suicide standardized incidence ratios (SIRs) among Europe-America and Asia-North Africa-born Israelis with cancer, relative to the respective rates in the general population. The SIRs were higher in the European-American group [men: 1.96, 95% confidence interval (CI) 1.62-2.30; women: 2.03, 95% CI 1.51-2.56], but not significantly different in the Asian-North African group (men: 0.86, 95% CI 0.52-1.20; women: 0.80, 95% CI 0.10-1.50). Assessment of suicide risk must consider the 'suicide culture' of the person with cancer.}, } @article {pmid22537207, year = {2013}, author = {Schapira, AH and Barone, P and Hauser, RA and Mizuno, Y and Rascol, O and Busse, M and Debieuvre, C and Fraessdorf, M and Poewe, W and , }, title = {Patient-reported convenience of once-daily versus three-times-daily dosing during long-term studies of pramipexole in early and advanced Parkinson's disease.}, journal = {European journal of neurology}, volume = {20}, number = {1}, pages = {50-56}, doi = {10.1111/j.1468-1331.2012.03712.x}, pmid = {22537207}, issn = {1468-1331}, mesh = {Aged ; Antiparkinson Agents/*administration & dosage ; Benzothiazoles/*administration & dosage ; Double-Blind Method ; Drug Administration Schedule ; Female ; Humans ; International Cooperation ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/*drug therapy ; Pramipexole ; *Self Report ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND AND PURPOSE: In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules.

METHODS:   In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire.

RESULTS:   Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar.

CONCLUSIONS:   In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.}, } @article {pmid22534285, year = {2012}, author = {Neto, GB and Rossetti, C and Souza, NA and LA Fonseca, F and Azzalis, LA and Junqueira, VB and Valenti, VE and de Abreu, LC}, title = {Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report.}, journal = {European journal of medical research}, volume = {17}, number = {1}, pages = {8}, pmid = {22534285}, issn = {2047-783X}, mesh = {*Breast Neoplasms/complications/pathology/surgery ; *Carcinoma, Ductal/complications/pathology/surgery ; Female ; Humans ; Neoplasm Invasiveness/*pathology ; *Phyllodes Tumor/complications/pathology/surgery ; }, abstract = {This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.}, } @article {pmid22531532, year = {2012}, author = {, and Permi, HS and Kishan Prasad, HL and Mohan, R and Shetty, KJ and Patil, C}, title = {Synchronous bilateral medullary carcinoma of breast: is it metastasis or second primary?.}, journal = {Journal of cancer research and therapeutics}, volume = {8}, number = {1}, pages = {129-131}, doi = {10.4103/0973-1482.95193}, pmid = {22531532}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*diagnosis/pathology/therapy ; Carcinoma, Medullary/*diagnosis/pathology/therapy ; Chemoradiotherapy ; Female ; Humans ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms, Second Primary/*diagnosis/pathology/therapy ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; }, abstract = {Bilateral breast cancer is a rare event accounting for 2-5% of all breast malignancies. A second tumor in contralateral breast may be either synchronous or metachronous lesion. Synchronous bilateral invasive ductal carcinoma is known but medullary carcinoma is rare. The etiology of bilateral breast cancer is uncertain and prognosis in these cases once thought to be poor but recent data suggest a similar survival compared to unilateral disease. We report a case of triple negative synchronous bilateral medullary carcinoma in a 38-year-old female who presented with lump in both the breasts for three months. Multidetector computed tomography breast scan revealed bilateral heterogeneously enhancing well-defined lesion in both the breasts. Fine needle aspiration cytology from both the breast lump was suggestive of malignancy. Patient underwent bilateral modified radical mastectomy with axillary clearance in a single sitting. Histopathology showed synchronous bilateral medullary carcinoma of breast with ER, PR and HER- 2/ neu negativity. Patient was treated with chemoradiation and she is on regular follow up for one year without any recurrence or metastasis.}, } @article {pmid22528931, year = {2012}, author = {Shin, HJ and Baek, HM and Cha, JH and Kim, HH}, title = {Evaluation of breast cancer using proton MR spectroscopy: total choline peak integral and signal-to-noise ratio as prognostic indicators.}, journal = {AJR. American journal of roentgenology}, volume = {198}, number = {5}, pages = {W488-97}, doi = {10.2214/AJR.11.7292}, pmid = {22528931}, issn = {1546-3141}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism ; Choline/*metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy/*methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Signal-To-Noise Ratio ; Statistics, Nonparametric ; }, abstract = {OBJECTIVE: The purpose of this article is to determine whether the peak integral and signal-to-noise ratio (SNR) of total choline-containing compounds obtained by MR spectroscopy (MRS) correlate with histologic biomarkers currently used for predicting prognosis in patients with breast cancer.

MATERIALS AND METHODS: Single-voxel proton MRS using a 1.5-T scanner was performed in 184 patients (mean age, 48 years; range, 28-72 years) with breast cancer. We obtained absolute total choline-containing compound peak integral, total choline-containing compound peak integral normalized for the volume of interest, and SNR after MRI. On surgical pathology, pathologic subtype and prognostic factors such as nuclear grade, histologic grade, estrogen receptor (ER), HER-2≠neu, extensive intraductal component (EIC), lymphovascular invasion, and lymph node metastasis were also evaluated. Statistical analysis was performed using Mann-Whitney U test and Spearman rank correlation.

RESULTS: The total choline-containing compound SNR, absolute total choline-containing compound peak integral, and normalized total choline-containing compound integral were significantly higher for invasive ductal carcinoma, cancer of high nuclear or histologic grade, and EIC-negative cancer (p < 0.001) than for in situ or other invasive carcinomas (p = 0.005), cancer of low nuclear or histologic grade (p = 0.009), and EIC-positive cancer (p = 0.017). There was a significant difference in the total choline-containing compound SNR between ER-positive and -negative groups (p = 0.007) and between triple-negative and non-triple-negative groups (p = 0.002). A positive correlation was found between the volume of interest (p < 0.001), tumor size (p = 0.011), and three MRS parameters (p = 0.003).

CONCLUSION: Our study suggests that proton MRS can play a role in predicting prognostic indicators of tumor aggressiveness in patients with newly diagnosed breast cancer.}, } @article {pmid22527124, year = {2012}, author = {Zheng, J and Liu, Q and Yang, J and Ren, Q and Cao, W and Yang, J and Yu, Z and Yu, F and Wu, Y and Shi, H and Liu, W}, title = {Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {45}, number = {6}, pages = {510-515}, pmid = {22527124}, issn = {1414-431X}, mesh = {Analysis of Variance ; Antibiotics, Antineoplastic/*pharmacology ; Apoptosis/*drug effects ; Breast Neoplasms/*immunology ; Cancer Vaccines/*immunology ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Doxorubicin/*pharmacology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma/metabolism ; Lymphocyte Activation ; MCF-7 Cells ; }, abstract = {A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.}, } @article {pmid22524846, year = {2012}, author = {Khokher, S and Qureshi, MU and Riaz, M and Akhtar, N and Saleem, A}, title = {Clinicopathologic profile of breast cancer patients in Pakistan: ten years data of a local cancer hospital.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {2}, pages = {693-698}, doi = {10.7314/apjcp.2012.13.2.693}, pmid = {22524846}, issn = {2476-762X}, mesh = {Adenocarcinoma, Mucinous/epidemiology/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Pakistan/epidemiology ; Prognosis ; Time Factors ; Young Adult ; }, abstract = {Breast cancer is the most frequent cancer of women worldwide, with considerable geographic and racial/ethnic variation. Data are generally derived from population based cancer registries in the developed countries but hospital data are the most reliable source in the developing countries. Ten years data from 1st Jan 2000 to 31st Dec 2009 of a cancer hospital in Pakistan were here analyzed by descriptive statistics to evaluate the clinicopathologic profile of local breast cancer patients. Among 28,740 cancer patients, 6,718 were registered as breast cancer. The female to male ratio was 100:2. Breast cancer accounted for 23% of all and 41% of female cancers. Some 46% were residents of Lahore, with a mean age of 47±12 years. Less than 1% were at Stage 0 and 10%, 32%, 35% and 23% were at Stage I, II, III and IV respectively. Histopathology was unknown in 4% while 91%, 2% and 1% had invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and mucinous carcinoma respectively. Rare carcinomas accounted for the rest. Tumor grade 1, 2 and 3 was 11%, 55% and 34% among the known. Profile of breast cancer patients in Pakistan follows a pattern similar to that of other developing countries with earlier peak age and advanced disease stage at presentation. The male breast cancer accounts for higher proportion in the local population. Local women have higher frequency of IDC and lower frequency of ILC and DCIS, owing probably to a different risk profile. Use of hospital information systems and establishment of population based cancer registry is required to have accurate and detailed local data. Promotion of breast health awareness and better health care system is required to decrease the burden of advanced disease.}, } @article {pmid22524806, year = {2012}, author = {Chuthapisith, S and Permsapaya, W and Warnnissorn, M and Akewanlop, C and Sirivatanauksorn, V and Prasarttong Osoth, P}, title = {Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {2}, pages = {459-462}, doi = {10.7314/apjcp.2012.13.2.459}, pmid = {22524806}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*classification/metabolism/pathology ; Carcinoma, Basal Cell/*classification/metabolism/pathology ; Carcinoma, Ductal, Breast/*classification/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Thailand ; }, abstract = {Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2+), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, χ2). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, χ2). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, χ2). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.}, } @article {pmid22524805, year = {2012}, author = {Ramezani, F and Salami, S and Omrani, MD and Maleki, D}, title = {CpG island methylation profile of estrogen receptor alpha in Iranian females with triple negative or non-triple negative breast cancer: new marker of poor prognosis.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {13}, number = {2}, pages = {451-457}, doi = {10.7314/apjcp.2012.13.2.451}, pmid = {22524805}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; CpG Islands/*genetics ; *DNA Methylation ; DNA, Neoplasm/genetics ; Estrogen Receptor alpha/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunoenzyme Techniques ; Iran ; Menopause ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Prognosis ; Promoter Regions, Genetic/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of ER gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-2 overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-2+ tumors and in postmenopausal patients with ER-, PgR-, or ER-/PgR- tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of ER-a gene frequently occur in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.}, } @article {pmid22523546, year = {2012}, author = {Wang, H and Tan, G and Dong, L and Cheng, L and Li, K and Wang, Z and Luo, H}, title = {Circulating MiR-125b as a marker predicting chemoresistance in breast cancer.}, journal = {PloS one}, volume = {7}, number = {4}, pages = {e34210}, pmid = {22523546}, issn = {1932-6203}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood ; Breast Neoplasms/*drug therapy/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; E2F3 Transcription Factor/drug effects/genetics ; Female ; Humans ; MicroRNAs/*blood ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Chemotherapy is an important component in the treatment paradigm for breast cancers. However, the resistance of cancer cells to chemotherapeutic agents frequently results in the subsequent recurrence and metastasis. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of circulating microRNAs (miRNAs) can predict clinical outcome in breast cancer patients treated with adjuvant chemotherapy.

Circulating miRNAs in blood serum prior to treatment were determined by quantitative Real-Time PCR in 56 breast cancer patients with invasive ductal carcinoma and pre-operative neoadjuvant chemotherapy. Proliferating cell nuclear antigen (PCNA) immunostaining and TUNEL were performed in surgical samples to determine the effects of chemotherapy on cancer cell proliferation and apoptosis, respectively. Among the miRNAs tested, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression level in non-responsive patients (n = 26, 46%; p = 0.008). In addition, breast cancers with high miR-125b expression had higher percentage of proliferating cells and lower percentage of apoptotic cells in the corresponding surgical specimens obtained after neoadjuvant chemotherapy. Increased resistance to anticancer drug was observed in vitro in breast cancer cells with ectopic miR-125b expression; conversely, reducing miR-125b level sensitized breast cancer cells to chemotherapy. Moreover, we demonstrated that the E2F3 was a direct target of miR-125b in breast cancer cells.

CONCLUSIONS/SIGNIFICANCE: These data suggest that circulating miR-125b expression is associated with chemotherapeutic resistance of breast cancer. This finding has important implications in the development of targeted therapeutics for overcoming chemotherapeutic resistance in novel anti-cancer strategies.}, } @article {pmid22515290, year = {2012}, author = {Ren, X and Daa, T and Yada, N and Kashima, K and Fujitomi, Y and Yokoyama, S}, title = {Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {120}, number = {5}, pages = {358-367}, doi = {10.1111/j.1600-0463.2011.02841.x}, pmid = {22515290}, issn = {1600-0463}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; DNA, Neoplasm/chemistry/genetics ; Female ; Hepatocyte Growth Factor/biosynthesis/genetics/*metabolism ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins/biosynthesis/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/biosynthesis/genetics/*metabolism ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to MET and involved in tumorigenesis. We investigated the roles of aberrations in RON and its ligand, macrophage-stimulating protein (MSP), in invasive ductal carcinoma (IDC, n = 81), ductal carcinoma in situ (DCIS, n = 26), and in benign lesions (n = 20) of mammary gland. Expression of RON and MSP was evaluated by immunohistochemistry and the mutational status of a region containing the proteolytic cleavage site in exon 1 and each exon of the kinase domain (exon 14-20) of RON was screened by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. The proportion of cases positive for RON expression was significantly different between malignant [86% (92/107)] and benign [40% (8/20)] lesions. RON expression was positive in both IDC and DCIS [90% (73/81) and 73% (19/26), respectively], whereas MSP expression was present in 54% (44/81) of IDC and absent in DCIS. RON expression correlated significantly with the histological grade of DCIS. No mutations were detected in the examined regions of RON in breast cancer samples as confirmed by PCR-SSCP. The findings suggest the involvement of RON expression in the development of breast cancer, and that an autocrine/paracrine loop of RON seems to affect tumor invasiveness.}, } @article {pmid22514560, year = {2012}, author = {Castellana, B and Escuin, D and Peiró, G and Garcia-Valdecasas, B and Vázquez, T and Pons, C and Pérez-Olabarria, M and Barnadas, A and Lerma, E}, title = {ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas.}, journal = {Journal of Cancer}, volume = {3}, number = {}, pages = {175-183}, pmid = {22514560}, issn = {1837-9664}, abstract = {UNLABELLED: The mechanism of progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR) and immunohistochemistry. Controls included seven pure in situ carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT).Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, and COL11A1), cellular adhesion (GJB2), cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, and ENPP2), extracellular matrix degradation (MMP11, MMP13, and MMP14), and growth/proliferation (ST6GAL2). qRT-PCR confirmed the expression patterns of ASPN, GJB2, ENPP2, ST6GAL2, and TMBS10. Expression of the ASPN and GJB2 gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors (P < 0.05).

CONCLUSIONS: The upregulation of ASPN and GJB2 may play important roles in local invasion of breast ductal carcinomas.}, } @article {pmid22507091, year = {2012}, author = {Noda, Y and Fujita, N and Kobayashi, G and Ito, K and Horaguchi, J and Obana, T and Koshita, S and Kanno, Y and Yamashita, Y and Kato, Y and Ogawa, T and Tsuchiya, T and Oikawa, M and Sawai, T and Kanno, H and Kurose, A}, title = {Prospective randomized controlled study comparing cell block method and conventional smear method for pancreatic juice cytology.}, journal = {Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society}, volume = {24}, number = {3}, pages = {168-174}, doi = {10.1111/j.1443-1661.2011.01180.x}, pmid = {22507091}, issn = {1443-1661}, mesh = {Aged ; Chi-Square Distribution ; Cholangiopancreatography, Endoscopic Retrograde ; Cytodiagnosis/*methods ; Diagnosis, Differential ; Female ; Humans ; Male ; Pancreatic Juice/*cytology ; Pancreatic Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Staining and Labeling ; }, abstract = {AIM: To elucidate the diagnostic efficacy of the cell block (CB) method by comparing it with that of conventional smear cytology for pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial fashion.

METHODS:   A total of 170 patients with pancreatic lesions suspicious of being malignant who underwent pancreatic juice collection without giving secretin under ERCP were enrolled in this study. After sampling, the pancreatic juice was randomized to the CB method (n = 85) or to smear cytology (n = 85). CB sections were subjected to hematoxylin-eosin, periodic acid Schiff-Alcian blue, and immunohistochemical stains. Both Papanicolaou stain and Giemsa stain were used for smear cytology.

RESULTS:   The final diagnosis was malignancy in 54 patients: pancreatic cancer, 45; intraductal papillary-mucinous carcinoma, six; and endocrine tumor, three. The number of patients with a cytological borderline malignancy in the CB group (3.5%) was significantly smaller than that in the smear group (27.1%) (P < 0.001). The diagnostic accuracy of the CB method and that of smear cytology were 76.5% (65/85) and 74.1% (63/85), respectively (P = 0.72), and their respective sensitivities were 50% (14/28) and 38.5% (10/26) (P = 0.39). The sensitivity of the CB method (88.9%) was better than that of smear cytology (42.9%) for invasive ductal carcinoma in the pancreas head (P = 0.048).

CONCLUSIONS:   The CB method using immunostaining for pancreatic juice cytology showed a much lower rate of equivocal borderline malignancy and a tendency for a higher diagnostic yield compared with smear cytology. Its diagnostic sensitivity, however, was not satisfactory except for pancreatic-head cancer.}, } @article {pmid22503535, year = {2012}, author = {de Oliveira, MM and de Oliveira, SF and Lima, RS and de Andrade Urban, C and Cavalli, LR and de Souza Fonseca Ribeiro, EM and Cavalli, IJ}, title = {Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas.}, journal = {Human pathology}, volume = {43}, number = {10}, pages = {1661-1667}, doi = {10.1016/j.humpath.2011.12.008}, pmid = {22503535}, issn = {1532-8392}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Chromosomes, Human, Pair 3/*genetics ; Female ; Humans ; Loss of Heterozygosity/*genetics ; Polymerase Chain Reaction ; }, abstract = {The 2 main histologic types of infiltrating breast cancer, invasive lobular and invasive ductal carcinoma, are morphologically and clinically distinct. Studies revealed that different patterns of gene expression and loss of heterozygosity can also distinguish these 2 subtypes. A whole-genome study using single nucleotide polymorphism array found a significantly higher frequency of loss of heterozygosity on 3p in invasive ductal carcinoma when compared with invasive lobular carcinoma. In this study, we performed a loss of heterozygosity analysis of the 3p chromosome region in ductal and lobular breast tumors. Seven microsatellite markers were evaluated in a series of 136 sporadic breast cancer cases (118 invasive ductal carcinoma and 18 invasive lobular carcinoma) and correlated with clinical-histopathologic parameters from the patients. A significantly higher frequency of loss of heterozygosity was observed in invasive ductal carcinoma (65.3%) when compared with invasive lobular carcinoma (38.9%). When the markers were analyzed separately, loss of heterozygosity at 3 of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3, and D3S1300 in 3p14.2, were significantly more frequent in ductal than in lobular tumors. D3S1307 marker showed the highest frequency of loss of heterozygosity in invasive ductal carcinoma (46.2%), and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples. Our results confirm the observations that invasive ductal carcinoma has a higher frequency of loss of heterozygosity events across the 3p region than invasive lobular carcinoma and show that specific losses on 3p26.3, 3p24.3, and 3p14.2 regions are more frequent in ductal than in lobular tumors. We discuss our data in relation to the known tumor suppressor genes that are mapped at the 3p loci investigated and their present relevant roles in breast cancer.}, } @article {pmid22499299, year = {2012}, author = {Gupta, S and Deka, L and Gupta, R and Pant, L and Singh, S}, title = {Molecular phenotypes of ductal carcinoma-in-situ and invasive ductal carcinoma: a comparative study.}, journal = {Indian journal of pathology & microbiology}, volume = {55}, number = {1}, pages = {43-46}, doi = {10.4103/0377-4929.94854}, pmid = {22499299}, issn = {0974-5130}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Histocytochemistry ; Humans ; Immunohistochemistry ; Keratins/*analysis ; Microscopy ; Middle Aged ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; }, abstract = {AIMS AND OBJECTIVES: This study was aimed at analyzing the prevalence of molecular phenotypes in invasive ductal carcinoma (IDC) and coexisting ductal carcinoma-in-situ (DCIS) and to correlate with clinicopathological features.

MATERIALS AND METHODS: In this study, 75 cases of IDC with coexisting DCIS were included. Molecular phenotype was determined using expression of estrogen receptor, progesterone receptor, HER2/neu, and cytokeratin 5/6. Statistical analysis was performed for correlation between molecular phenotypes and clinicopathologic parameters.

RESULTS: Of the 75 cases, the invasive component in all cases was IDC--not otherwise specified. About one-third of our patients were post-menopausal. The most common molecular phenotype was luminal A (45.3%) followed by HER2-expressing type (24%). In all cases, the molecular phenotype was identical in DCIS and the invasive component. HER2-expressing tumors were found to be larger in size with frequent nodal involvement. On statistical analysis, tumor size and grade were found to correlate with the molecular phenotype.

CONCLUSION: In conclusion, the molecular phenotype in DCIS correlates well with that of coexisting IDC, suggesting that DCIS is a precursor lesion in these tumors. This correlation of molecular phenotype can be utilized in prediction of phenotype of the invasive component in a case with in-situ carcinoma.}, } @article {pmid22498883, year = {2012}, author = {Hodgkinson, VC and Agarwal, V and ELFadl, D and Fox, JN and McManus, PL and Mahapatra, TK and Kneeshaw, PJ and Drew, PJ and Lind, MJ and Cawkwell, L}, title = {Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer.}, journal = {Journal of proteomics}, volume = {75}, number = {9}, pages = {2745-2752}, doi = {10.1016/j.jprot.2012.03.049}, pmid = {22498883}, issn = {1876-7737}, mesh = {14-3-3 Proteins/*genetics ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/genetics ; Drug Resistance, Neoplasm/*genetics ; Electrophoresis, Gel, Two-Dimensional ; Feasibility Studies ; Female ; Humans ; Neoadjuvant Therapy ; Pilot Projects ; Receptors, Estrogen/genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Neoadjuvant chemotherapy is used to treat oestrogen receptor-positive breast cancer however chemo-resistance is a major obstacle in this molecular subtype. The ability to predict tumour response would allow chemotherapy administration to be directed towards patients who would most benefit, thus maximising treatment efficacy. We aimed to identify protein biomarkers associated with response to neoadjuvant chemotherapy, in a pilot study using comparative 2-DE MALDI TOF/TOF MS proteomic analysis of breast tumour samples. A total of 3 comparative proteomic experiments were performed, comparing protein expression between chemotherapy-sensitive and chemotherapy-resistant oestrogen receptor-positive invasive ductal carcinoma tissue samples. This identified a list of 132 unique proteins that were significantly differentially expressed (≥ 2 fold) in chemotherapy resistant samples, 57 of which were identified in at least two experiments. Ingenuity® Pathway Analysis was used to map the 57 DEPs onto canonical signalling pathways. We implicate several isoforms of 14-3-3 family proteins (theta/tau, gamma, epsilon, beta/alpha and zeta/delta), which have previously been associated with chemotherapy resistance in breast cancer. Extensive clinical validation is now required to fully assess the role of these proteins as putative markers of chemotherapy response in luminal breast cancer subtypes.}, } @article {pmid22496928, year = {2012}, author = {Sens-Abuázar, C and Napolitano E Ferreira, E and Osório, CA and Krepischi, AC and Ricca, TI and Castro, NP and da Cunha, IW and Maciel, Mdo S and Rosenberg, C and Brentani, MM and Soares, FA and Rocha, RM and Carraro, DM}, title = {Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.}, journal = {Translational oncology}, volume = {5}, number = {2}, pages = {113-123}, pmid = {22496928}, issn = {1936-5233}, abstract = {Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.}, } @article {pmid22495877, year = {2012}, author = {Hammadi, M and Chopin, V and Matifat, F and Dhennin-Duthille, I and Chasseraud, M and Sevestre, H and Ouadid-Ahidouch, H}, title = {Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.}, journal = {Journal of cellular physiology}, volume = {227}, number = {12}, pages = {3837-3846}, doi = {10.1002/jcp.24095}, pmid = {22495877}, issn = {1097-4652}, mesh = {Breast Neoplasms/metabolism/pathology ; Calcium/*metabolism ; Calcium Channels/genetics/*metabolism ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/*physiology ; Cell Survival ; Ether-A-Go-Go Potassium Channels/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Manganese ; Neoplasm Invasiveness ; ORAI1 Protein ; Patch-Clamp Techniques ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.}, } @article {pmid22493641, year = {2012}, author = {Baek, JM and Lee, JA and Nam, YH and Sung, GY and Lee, DS and Won, JM}, title = {Chylous leakage: a rare complication after axillary lymph node dissection in breast cancer and surgical management.}, journal = {Journal of breast cancer}, volume = {15}, number = {1}, pages = {133-134}, pmid = {22493641}, issn = {2092-9900}, abstract = {Chylous leakage is an extremely rare complication of surgery for breast cancer. We experienced a case of chylous leakage after axillary lymph node dissection. A 38-year-old woman with invasive ductal carcinoma in the left breast underwent a modified radical mastectomy after four cycles of neoadjuvant chemotherapy. The postoperative serosanguinous drainage fluid became "milky" on the fourth postoperative day. After trying conservative management, we re-explored the axilla and ligated the lymphatic trunk. Although the success of many cases supports conservative management, timely surgical intervention represents an alternative in cases where leakage persists or where the output is high.}, } @article {pmid22491004, year = {2012}, author = {Connolly, RM and Bardia, A}, title = {Trastuzumab for small HER-2+ breast cancer: small tumor, big decision.}, journal = {The oncologist}, volume = {17}, number = {4}, pages = {508-511}, pmid = {22491004}, issn = {1549-490X}, mesh = {Antibodies, Monoclonal, Humanized/administration & dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*drug therapy/*enzymology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Trastuzumab ; }, abstract = {A 53-year-old postmenopausal woman was found to have a new area of microcalcification at the 10 o'clock position of her right breast during a routine screening mammogram. Ultrasound-guided core biopsy revealed a grade 2 invasive ductal carcinoma, estrogen receptor (ER)+ (90%), progesterone receptor positive (20%), and human epidermal growth factor receptor (HER)-2+ (3+ by immunohistochemistry). A right breast lumpectomy and sentinel node biopsy were performed. The invasive tumor measured 0.7 cm, no lymphovascular space invasion was identified, surgical margins were uninvolved, and the sentinel lymph nodes were negative for tumor. She was evaluated postoperatively in the medical oncology clinic to discuss an adjuvant treatment strategy. The question for our colleagues is: should she be offered adjuvant chemotherapy and trastuzumab prior to adjuvant radiation and 5 years of hormonal therapy?}, } @article {pmid22489664, year = {2012}, author = {Krell, J and Frampton, AE and Jacob, J and Pellegrino, L and Roca-Alonso, L and Zeloof, D and Alifrangis, C and Lewis, JS and Jiao, LR and Stebbing, J and Castellano, L}, title = {The clinico-pathologic role of microRNAs miR-9 and miR-151-5p in breast cancer metastasis.}, journal = {Molecular diagnosis & therapy}, volume = {16}, number = {3}, pages = {167-172}, pmid = {22489664}, issn = {1179-2000}, support = {10-0510/AICR_/Worldwide Cancer Research/United Kingdom ; G1100425/MRC_/Medical Research Council/United Kingdom ; NIHR-RP-011-053/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) may function as suppressors or promoters of tumor metastasis according to their messenger RNA targets. Previous studies have suggested that miR-9 and miR-151-5p are associated with metastasis in breast cancer and hepatocellular carcinoma, respectively. We aimed to further establish the potential roles of miR-9 and miR-151-5p in tumor invasion and metastasis and investigate their use as biomarkers.

METHODS: We used quantitative real-time PCR (qRT-PCR) to measure differences in miR-9 and miR-151-5p expression between primary breast tumors and their lymph-node metastases in 194 paired tumor samples from 97 patients. We also correlated expression levels with histologic data to investigate their utility as biomarkers.

RESULTS: There were no significant differences in miR-9 expression between the primary tumors and lymph nodes; however, miR-151-5p expression was significantly lower in the lymph-node metastases than in their corresponding tumors (p < 0.05). miR-9 levels were elevated in primary breast tumors from patients diagnosed with higher-grade tumors (p < 0.05); however, no differences were observed in miR-151-5p levels between different grades of tumor. Interestingly, miR-9 levels were elevated in invasive lobular carcinomas (ILC) compared with invasive ductal carcinomas (IDC; p < 0.01).

CONCLUSIONS: In aggregate, these data suggest that miR-151-5p upregulation may suppress metastasis in primary breast tumors. Both miRNAs may serve as useful biomarkers in future clinical trials in breast cancer.}, } @article {pmid22484590, year = {2012}, author = {Wang, GY and Zhang, Q and Yang, Y and Chen, WJ and Liu, W and Jiang, N and Chen, GH}, title = {Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats.}, journal = {Hepatobiliary & pancreatic diseases international : HBPD INT}, volume = {11}, number = {2}, pages = {203-208}, doi = {10.1016/s1499-3872(12)60149-0}, pmid = {22484590}, issn = {1499-3872}, mesh = {Animals ; CD4 Antigens/*metabolism ; Dendritic Cells/*transplantation ; Forkhead Transcription Factors/*metabolism ; Immune Tolerance/immunology ; Immunosuppressive Agents/pharmacology ; In Vitro Techniques ; Interferon-gamma/blood ; Interleukin-2/blood ; Interleukin-2 Receptor alpha Subunit/*metabolism ; Interleukin-4/blood ; Models, Animal ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Sirolimus/*pharmacology ; T-Lymphocytes, Regulatory/*drug effects/*immunology/pathology ; Transforming Growth Factor beta1/blood ; Transplantation Tolerance/immunology ; }, abstract = {BACKGROUND: Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model.

METHODS: Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated.

RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups.

CONCLUSIONS: A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.}, } @article {pmid22482764, year = {2012}, author = {Gainer, SM and Lodhi, AK and Bhattacharyya, A and Krishnamurthy, S and Kuerer, HM and Lucci, A}, title = {Invasive lobular carcinoma predicts micrometastasis in breast cancer.}, journal = {The Journal of surgical research}, volume = {177}, number = {1}, pages = {93-96}, pmid = {22482764}, issn = {1095-8673}, support = {R21 DK067682/DK/NIDDK NIH HHS/United States ; R21 DK067682-01/DK/NIDDK NIH HHS/United States ; R21 DK067682-02/DK/NIDDK NIH HHS/United States ; R21-DK067682/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Middle Aged ; *Neoplasm Micrometastasis ; *Neoplastic Cells, Circulating ; Prospective Studies ; }, abstract = {BACKGROUND: Invasive lobular carcinomas (ILCs) are almost always estrogen receptor (ER) positive. Most delayed breast cancer recurrences occur in ER-positive patients. Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been implicated in recurrence. The purpose of this study was to determine whether DTCs and CTCs are associated with ILCs in stage I-III breast cancer.

MATERIALS AND METHODS: Clinical stage I-III breast cancer patients consented to participate in an institutional review board-approved study involving collection of bone marrow and blood at surgery for primary breast cancer. We assessed DTCs by anti-CK antibody cocktail after cytospin. We detected CTCs using CellSearch, and defined them as nucleated cells lacking CD45 but expressing cytokeratin. One or more cells per 5 mL bone marrow or 7.5 mL blood was considered positive. We performed statistical analyses using chi-square and Fisher's exact tests.

RESULTS: We prospectively enrolled 422 patients, 64 with ILC and 358 with invasive ductal carcinoma. Estrogen receptor positivity was higher in ILCs (92.2% versus 66.2%) {P = .001} . We identified DTCs to be 43.4% with ILC compared with 28.9% with IDC {P = 0.03} . The CTC rates were similar. Either DTCs or CTCs were identified in 75.6% with ILC, compared with 51.7% with invasive ductal carcinoma {P = .002} . We observed no correlation between the presence of DTCs and CTCs in ILC patients and tumor size, grade, hormone receptor status, stage, lymph node status, or administration of NACT.

CONCLUSIONS: Invasive lobular carcinomas independently predicted micrometastatic disease. Because most late recurrences are ER positive, this raises the question of whether DTCs and CTCs are indeed responsible for late breast cancer recurrence.}, } @article {pmid22475781, year = {2012}, author = {Lee, Y and Ryu, Y and Jeong, H and Chang, H and Kim, Y and Kim, A}, title = {Effectiveness of silver-enhanced in situ hybridization for evaluating HER2 gene status in invasive breast carcinoma: a comparative study.}, journal = {Archives of medical research}, volume = {43}, number = {2}, pages = {139-144}, doi = {10.1016/j.arcmed.2012.03.010}, pmid = {22475781}, issn = {1873-5487}, mesh = {Breast Neoplasms/*genetics/pathology ; *Genes, erbB-2 ; Humans ; In Situ Hybridization/*methods ; Neoplasm Invasiveness ; Silver/*chemistry ; }, abstract = {BACKGROUND AND AIMS: HER2 gene amplification occurs in breast cancers and has implications for treatment and prognosis. Recently, a new direct evaluation technique, silver enhanced in situ hybridization (SISH) was developed for evaluating HER2 gene status. This study was performed to evaluate the SISH technique for clinical use by comparing it to that of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).

METHODS: We studied 543 cases of excised breast specimens diagnosed as invasive ductal carcinoma by IHC, FISH, and SISH using a tissue microarray. IHC, FISH, and SISH results were interpreted according to the American Society of Clinical Oncology/College of American Pathologists guidelines. A total of seven English studies that reported the concordance rates of SISH and BDISH compared to FISH published before July 2011 were retrieved.

RESULTS: The consensus concordance rate between SISH and FISH was 96.69% (kappa value = 0.9175). The pooled sensitivity was 0.94 [95% confidence interval (CI) = 0.91-0.97], and the pooled specificity was 0.98 (95% CI = 0.96-099) in a meta-analysis of the retrieved studies and this study. Area under the receiver operating characteristics curve was 0.9906.

CONCLUSIONS: SISH technique is an effective modality and is comparable with FISH for evaluating HER2 gene amplification in patients with breast carcinoma.}, } @article {pmid22472881, year = {2012}, author = {Xu, C and Tran-Thanh, D and Ma, C and May, K and Jung, J and Vecchiarelli, J and Done, SJ}, title = {Mitochondrial D310 mutations in the early development of breast cancer.}, journal = {British journal of cancer}, volume = {106}, number = {9}, pages = {1506-1511}, pmid = {22472881}, issn = {1532-1827}, mesh = {Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA, Mitochondrial/*genetics ; Disease Progression ; Female ; Humans ; Mutation/*genetics ; Repetitive Sequences, Nucleic Acid/genetics ; }, abstract = {BACKGROUND: The role of mitochondrial DNA (mtDNA) mutations in the development of breast cancer is largely unknown. In this study, we investigated the frequency and pattern of mutations in the D310 region, the most commonly mutated region in mtDNA, in a series of breast lesions.

METHODS: Using capillary electrophoresis, we genotyped the D310 sequence of neoplastic epithelial cells from 23 patients with synchronous ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), 26 patients with IDC only and 29 patients with DCIS only.

RESULTS: A majority of DCIS (68.4%) and IDC (71.4%) lesions harbour different D310 sequences compared with their matched normal control. Specific D310 sequences were more frequently identified in tumour samples (77.1% of DCIS and 75.5% of IDC) compared with normal tissues (35.3% of normal; P<0.0001). No difference was identified between DCIS lesions with synchronous IDC and those from pure DCIS cases. In five cases, histologically normal tissue adjacent to tumour was found to share D310 sequences with the tumour, while normal tissue taken further away did not.

CONCLUSION: Although D310 alterations do not seem to be related to DCIS progression, they were found in histologically normal cells adjacent to tumour. This suggests a field of genetically altered cells, thus D310 mutations could represent a potential marker for the clonal expansion of premalignant breast cancer cells.}, } @article {pmid22472011, year = {2012}, author = {Aiello Bowles, EJ and Feigelson, HS and Barney, T and Broecker, K and Sterrett, A and Bischoff, K and Engel, J and Gundersen, G and Sheehey-Jones, J and Single, R and Onitilo, A and James, TA and McCahill, LE}, title = {Improving quality of breast cancer surgery through development of a national breast cancer surgical outcomes (BRCASO) research database.}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {136}, pmid = {22472011}, issn = {1471-2407}, support = {P01 CA154292/CA/NCI NIH HHS/United States ; 1RC1 CA145402/CA/NCI NIH HHS/United States ; U19 CA 79689/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*surgery ; Carcinoma/pathology/*surgery ; Databases, Factual ; Female ; Health Planning/methods ; Humans ; Middle Aged ; *Outcome Assessment, Health Care ; Quality Assurance, Health Care/*methods ; United States ; Young Adult ; }, abstract = {BACKGROUND: Common measures of surgical quality are 30-day morbidity and mortality, which poorly describe breast cancer surgical quality with extremely low morbidity and mortality rates. Several national quality programs have collected additional surgical quality measures; however, program participation is voluntary and results may not be generalizable to all surgeons. We developed the Breast Cancer Surgical Outcomes (BRCASO) database to capture meaningful breast cancer surgical quality measures among a non-voluntary sample, and study variation in these measures across providers, facilities, and health plans. This paper describes our study protocol, data collection methods, and summarizes the strengths and limitations of these data.

METHODS: We included 4524 women ≥18 years diagnosed with breast cancer between 2003-2008. All women with initial breast cancer surgery performed by a surgeon employed at the University of Vermont or three Cancer Research Network (CRN) health plans were eligible for inclusion. From the CRN institutions, we collected electronic administrative data including tumor registry information, Current Procedure Terminology codes for breast cancer surgeries, surgeons, surgical facilities, and patient demographics. We supplemented electronic data with medical record abstraction to collect additional pathology and surgery detail. All data were manually abstracted at the University of Vermont.

RESULTS: The CRN institutions pre-filled 30% (22 out of 72) of elements using electronic data. The remaining elements, including detailed pathology margin status and breast and lymph node surgeries, required chart abstraction. The mean age was 61 years (range 20-98 years); 70% of women were diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and 10% with invasive lobular carcinoma.

CONCLUSIONS: The BRCASO database is one of the largest, multi-site research resources of meaningful breast cancer surgical quality data in the United States. Assembling data from electronic administrative databases and manual chart review balanced efficiency with high-quality, unbiased data collection. Using the BRCASO database, we will evaluate surgical quality measures including mastectomy rates, positive margin rates, and partial mastectomy re-excision rates among a diverse, non-voluntary population of patients, providers, and facilities.}, } @article {pmid22470069, year = {2012}, author = {Chang, EI and Peled, AW and Foster, RD and Lin, C and Zeidler, KR and Ewing, CA and Alvarado, M and Hwang, ES and Esserman, LJ}, title = {Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy.}, journal = {Annals of surgery}, volume = {255}, number = {6}, pages = {1151-1157}, doi = {10.1097/SLA.0b013e31824f9769}, pmid = {22470069}, issn = {1528-1140}, mesh = {Breast Neoplasms/pathology/*surgery ; Feasibility Studies ; Female ; Humans ; *Mammaplasty ; *Mastectomy, Segmental ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVES: To assess the efficacy of using concurrent partial mastectomy and reduction mammoplasty for resection of a wide range of tumor sizes and compare oncologic outcomes and postoperative complications on the basis of tumor size.

BACKGROUND: Although tumor size greater than 4 cm has been considered an indication for undergoing a mastectomy, this dictum may not apply in women with breast hypertrophy, where the ratio of tumor size to breast size may still permit breast conservation. We wished to evaluate whether an approach combining partial mastectomy with reduction mammoplasty could provide a safe oncologic procedure with immediate breast reconstruction that could technically be applied even for large (>4 cm) lesions.

METHODS: A retrospective review of all patients undergoing partial mastectomy and concurrent reduction mammoplasty performed at our institution from 2000 to 2009. Clinical characteristics at presentation, pathologic data, and follow-up data were collected and analyzed.

RESULTS: Eighty-five consecutive simultaneous partial mastectomy/reduction mammoplasty procedures were performed in 79 patients. Average tumor size was 2.8 cm for ductal carcinoma in situ (0.05-17.0 cm), 2.4 cm for invasive ductal carcinoma (IDC) (0.2-8.9 cm), 3.5 cm for lobular carcinoma (1.6-8.0 cm), and 5.7 cm for phyllodes tumors (3.7-7.6 cm). Twenty-five of 85 tumors (29.4%) were larger than 4 cm. Distribution for stage 0, I, II, III, and IV disease was 15, 12, 35, 19, and 2 tumors respectively, with an additional 2 phyllodes tumors. Median follow-up was 39 months (10-130 months). Seventy-five patients (94.9%) achieved successful breast conservation, whereas 4 patients (5.1%) went on to completion mastectomy. Thirteen patients (16.4%) required 1 reexcision to achieve clear margins, and 2 (2.5%) required multiple reexcisions. Two patients had a local recurrence during the follow-up period, one of whom underwent reexcision and the other underwent mastectomy. The overall complication rate was 14.1%, which included 4 major complications (4.7%) requiring an unplanned return to the operating room and need for hospital readmission, and 8 minor wound-related complications (9.4%). Neither recurrence nor complication rates were increased in patients with tumors greater than 4 cm when compared with tumors less than or equal to 4 cm.

CONCLUSIONS: A partial mastectomy with concurrent reduction mammoplasty technique is a viable option for breast conservation even for larger tumors, combining a safe oncologic procedure with excellent cosmesis. A combined effort between breast surgeons and reconstructive surgeons has a high probability of success with low recurrence rates. In carefully selected patients, this approach may be preferable to mastecomy and breast reconstruction, particularly when postmastectomy radiation therapy is anticipated.}, } @article {pmid22468193, year = {2012}, author = {Watanabe, M and Shiozawa, K and Mimura, T and Ito, K and Kamata, I and Kishimoto, Y and Momiyama, K and Igarashi, Y and Sumino, Y}, title = {Hepatic artery pseudoaneurysm after endoscopic biliary stenting for bile duct cancer.}, journal = {World journal of radiology}, volume = {4}, number = {3}, pages = {115-120}, pmid = {22468193}, issn = {1949-8470}, abstract = {We report a case of a pseudoaneurysm of the right hepatic artery observed 9 mo after the endoscopic placement of a Wallstent, for bile duct stenosis, which was treated with transcatheter arterial embolization. The patient presented with obstructive jaundice and was diagnosed with inoperable common bile duct cancer. A plastic stent was inserted endoscopically to drain the bile, and chemotherapy was initiated. Abdominal pain and jaundice appeared approximately 6 mo after the beginning of chemotherapy. A diagnosis of stent occlusion and cholangitis was made, and the plastic stent was removed and substituted with a self-expandable metallic stent (SEMS) endoscopically. Nine months after SEMS insertion, contrast-enhanced computed tomography showed a pseudoaneurysm of the right hepatic artery protruding into the common bile duct lumen and in contact with the SEMS. The shape and size of the pseudoaneurysm and diameter of its neck was determined by contrast-enhanced ultrasonography using Sonazoid. A micro-catheter was led into the pseudoaneurysm in the right hepatic artery, GDC™ Detachable Coils were placed, and IDC™ Detachable Coils were then placed in the right hepatic artery on the distal and proximal sides of the pseudoaneurysm using the isolation method. There have been a few reports on pseudoaneurysm associated with stent placement in the biliary tract employing percutaneous transhepatic procedures, however, reports of pseudoaneurysms associated with endoscopic SEMS placement are very rare.}, } @article {pmid22458904, year = {2012}, author = {Robinson, B and Magi-Galluzzi, C and Zhou, M}, title = {Intraductal carcinoma of the prostate.}, journal = {Archives of pathology & laboratory medicine}, volume = {136}, number = {4}, pages = {418-425}, doi = {10.5858/arpa.2011-0519-RA}, pmid = {22458904}, issn = {1543-2165}, mesh = {Biopsy ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Diagnosis, Differential ; Humans ; Male ; Molecular Biology ; Prognosis ; Prostate/*pathology ; Prostatectomy ; Prostatic Neoplasms/genetics/*pathology ; }, abstract = {CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity, characterized by an expansile proliferation of secretory cells within prostatic ducts and acini that demonstrate marked architectural and cytologic atypia. Intraductal carcinoma of the prostate is strongly associated with high-grade and high-volume, invasive prostate cancer and a poorer prognosis than cases without IDC-P.

OBJECTIVE: To review the historic perspectives, pathologic and genetic features, diagnostic criteria and differential diagnoses, and the clinical significance of IDC-P.

DATA SOURCES: Relevant studies indexed in PubMed.

CONCLUSIONS: It is critical to recognize IDC-P, especially in prostate biopsies in which the clinical implications of IDC-P are greatest. Morphologic criteria have been proposed to distinguish IDC-P from several other lesions with similar histologic appearance such as high-grade prostatic intraepithelial neoplasia, invasive cribriform prostate cancer, and urothelial carcinoma involving the prostate. Intraductal carcinoma of the prostate is an uncommon finding in prostate biopsies, and it is even rarer as an isolated finding without concomitant prostate cancer in biopsies. However, patients with isolated IDC-P in biopsies are recommended for either definitive treatment or immediate repeat biopsy.}, } @article {pmid22455563, year = {2012}, author = {Xu, X and Jin, H and Liu, Y and Liu, L and Wu, Q and Guo, Y and Yu, L and Liu, Z and Zhang, T and Zhang, X and Dong, X and Quan, C}, title = {The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {33}, pmid = {22455563}, issn = {1746-1596}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Claudins/analysis/biosynthesis ; Female ; Histone Deacetylase 1/analysis/biosynthesis ; Histones/analysis/biosynthesis ; Humans ; Immunohistochemistry ; Methyl-CpG-Binding Protein 2/analysis/biosynthesis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Repressor Proteins/analysis/biosynthesis ; }, abstract = {BACKGROUND: Claudin-6 is a candidate tumor suppressor gene in breast cancer, and has been shown to be regulated by DNA methylation and histone modification in breast cancer lines. However, the expression of claudin-6 in breast invasive ductal carcinomas and correlation with clinical behavior or expression of other markers is unclear. We considered that the expression pattern of claudin-6 might be related to the expression of DNA methylation associated proteins (methyl-CpG binding protein 2 (MeCP2) and DNA methyltransferase 1 (DNMT1)) and histone modification associated proteins (histone deacetylase 1 (HDAC1), acetyl-histone H3 (H3Ac) and acetyl- histone H4 (H4Ac)).

METHODS: We have investigated the expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using immunohistochemistry.

RESULTS: Claudin-6 protein expression was reduced in breast invasive ductal carcinomas (P < 0.001). In contrast, expression of MeCP2 (P < 0.001), DNMT1 (P = 0.001), HDAC1 (P < 0.001) and H3Ac (P = 0.004) expressions was increased. Claudin-6 expression was inversely correlated with lymph node metastasis (P = 0.021). Increased expression of HDAC1 was correlated with histological grade (P < 0.001), age (P = 0.004), clinical stage (P = 0.007) and lymph node metastasis (P = 0.001). H3Ac expression was associated with tumor size (P = 0.044) and clinical stage of cancers (P = 0.034). MeCP2, DNMT1 and H4Ac expression levels did not correlate with any of the tested clinicopathological parameters (P > 0.05). We identified a positive correlation between MeCP2 protein expression and H3Ac and H4Ac protein expression.

CONCLUSIONS: Our results show that claudin-6 protein is significantly down-regulated in breast invasive ductal carcinomas and is an important correlate with lymphatic metastasis, but claudin-6 down-regulation was not correlated with upregulation of the methylation associated proteins (MeCP2, DNMT1) or histone modification associated proteins (HDAC1, H3Ac, H4Ac). Interestingly, the expression of MeCP2 was positively correlated with the expression of H3Ac and H3Ac protein expression was positively correlated with the expression of H4Ac in breast invasive ductal carcinoma

VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4549669866581452.}, } @article {pmid22452996, year = {2012}, author = {Xiang, L and Liu, ZH and Huan, Q and Su, P and Du, GJ and Wang, Y and Gao, P and Zhou, GY}, title = {Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma.}, journal = {Diagnostic pathology}, volume = {7}, number = {}, pages = {32}, pmid = {22452996}, issn = {1746-1596}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/*biosynthesis ; Basic Helix-Loop-Helix Transcription Factors/*biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Neoplasm Grading ; Neoplasm Proteins/*biosynthesis ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a) to the drug resistance and the clinicopathological characteristics in breast cancer.

METHODS: Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated.

RESULTS: The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001), histology-grade (p = 0.029), and Ki67 (p = 0. 043) respectively.

CONCLUSION: HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance.

VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795.}, } @article {pmid22451233, year = {2012}, author = {Cao, AY and He, M and Liu, ZB and Di, GH and Wu, J and Lu, JS and Liu, GY and Shen, ZZ and Shao, ZM}, title = {Outcome of pure mucinous breast carcinoma compared to infiltrating ductal carcinoma: a population-based study from China.}, journal = {Annals of surgical oncology}, volume = {19}, number = {9}, pages = {3019-3027}, doi = {10.1245/s10434-012-2322-6}, pmid = {22451233}, issn = {1534-4681}, mesh = {Adenocarcinoma, Mucinous/metabolism/*pathology/secondary/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary/therapy ; Chemotherapy, Adjuvant ; China ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {PURPOSE: Pure mucinous breast carcinoma (PMBC) is a rare pathologic finding. Few studies have addressed the biologic features of PMBC and prognostic factors among patients with this disease. We performed a study to compare PMBC and invasive ductal carcinoma (IDC) by means of a large database to reliably assess the biologic phenotype and clinical behavior of PMBC.

METHODS: A total of 2,511 patients who met the inclusion criteria were identified from 1999 to 2010; 2,202 patients had pure IDC and 309 had PMBC. Clinical and biologic features, overall survival, and recurrence/metastasis-free survival (RFS) were compared for both groups.

RESULTS: PMBC had favorable characteristics including smaller size, lower rates of lymph node positivity, lower stage, higher expression of hormone receptors, and less HER2 overexpression. Patients with PMBC had better 10-year RFS (71 %) than patients with IDC (64 %). Multivariate analysis revealed that node status and tumor, node, metastasis system (TNM) stage were statistically significant prognostic factors for survival. RFS curves stratified for node status revealed a highly significant difference between node negative and node positive patients. Additionally, patients with PMBC underwent breast-conserving surgery (BCS) more frequently than patients with IDC, and the 5-year overall survival rate of the BCS group was not significantly different from the total mastectomy group.

CONCLUSIONS: PMBC in Chinese women showed less aggressive behavior and had a better prognosis than IDC, and this favorable outcome was maintained after 10 years. Node status and TNM stage appeared to be the most significant predictors of worse prognosis. BCS should be preferred over mastectomy in the treatment of early-stage PMBC.}, } @article {pmid22451184, year = {2012}, author = {Rustamadji, P}, title = {NM23HI as marker of metastasis in invasive ductal breast cancer.}, journal = {Acta medica Indonesiana}, volume = {44}, number = {1}, pages = {40-46}, pmid = {22451184}, issn = {0125-9326}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases/*metabolism ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Odds Ratio ; ROC Curve ; }, abstract = {AIM: to examine the presence of metastasis marker in various histological malignancies of ductal breast carcinoma using NM23HI protein.

METHODS: paraffin blocks were obtained from 97 patients with invasive breast ductal cancer with 1, 2, 3 grade of malignancy from 2000 to early 2006 in several hospitals in Jakarta and Bandung. Examination began with histophatologic examination of eosin hematoxylin slides to diagnose the case of invasive ductal cancer and to get the data on the degree of histologic malignancy, metastasis or non-metastasis cases. It then continued to immunohistochemistry examination of NM23HI, and cytokeratin.

RESULTS: subjects were 29-75 years old with the mean of 48.19 years; most subjects were 40-45 years old with malignancy grade 1 numbering 18.56%; grade 2, 45.36%; and grade 3, 36.1%. Ninety seven paraffin blocks were examined from 2000 to 2006. There was a significant relationship between NM23HI expression in primary tumor with the possibility of inhibition of invasion and metastasis 11 times of those of negative expression of NM23HI. The ROC curve showed that NM23HI expression was strongly correlated (r=0.816) sensitive and specific as metastasis marker. NM23HI expression did not show significant relationship with histologic degree of invasive ductal carcinoma.

CONCLUSION: NM23HI expressions can be used as invasion and metastasis markers, but cannot be used as markers for the degree of histologic malignancy of invasive ductal cancer.}, } @article {pmid22450930, year = {2012}, author = {Tsutsumi, Y}, title = {Apocrine carcinoma as triple-negative breast cancer: novel definition of apocrine-type carcinoma as estrogen/progesterone receptor-negative and androgen receptor-positive invasive ductal carcinoma.}, journal = {Japanese journal of clinical oncology}, volume = {42}, number = {5}, pages = {375-386}, doi = {10.1093/jjco/hys034}, pmid = {22450930}, issn = {1465-3621}, mesh = {Adult ; Aged ; Apocrine Glands/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Carrier Proteins/metabolism ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Glycoproteins/metabolism ; Humans ; Immunohistochemistry ; Keratin-14/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Ki-67 Antigen/metabolism ; Membrane Transport Proteins ; Middle Aged ; Receptor, ErbB-2/*metabolism ; Receptors, Androgen/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Sweat Gland Neoplasms/*metabolism/pathology ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation ; }, abstract = {OBJECTIVE: Apocrine carcinoma, a subtype of invasive ductal carcinoma of the breast, expresses androgen receptor (AR), but often lacks estrogen receptor (ER) and progesterone receptor (PgR). In the present study, the author immunohistochemically defined apocrine-type carcinoma as ER-/PgR-/AR+ invasive ductal carcinoma and analyzed the significance of apocrine-type carcinoma as triple-negative breast cancer.

METHODS: Four hundred and forty breast cancers from 429 cases were immunostained for estrogen receptor, progesterone receptor, androgen receptor, human epidermal growth factor receptor type 2 (HER2), p53, Ki-67 and epidermal growth factor receptor. The lesions included 58 in situ malignancies (including 13 apocrine-type lesions) and 325 invasive ductal carcinomas (including 44 apocrine type).

RESULTS: Of 91 estrogen receptor-negative invasive ductal carcinomas, 44 (48%) belonged to apocrine-type carcinoma, and overexpression of human epidermal growth factor receptor type 2 and p53 was observed in 23 (52%) and 33 (75%), respectively. Histologically, 22 (50%) were categorized as classical apocrine carcinoma. Among 281 non-apocrine invasive ductal carcinomas, 30 (11%) were quadruple-negative (ER-/PgR-/AR-/HER2-) and 17 (6%) were hormone receptor-negative and human epidermal growth factor receptor type 2-overexpressed. Invasive ductal carcinomas in the triple-negative breast cancer category (n= 51) were divided into triple-negative, androgen receptor-positive (apocrine, n= 21) and quadruple-negative (non-apocrine, n= 30). p53 overexpression was more often seen in the apocrine-type triple-negative breast cancer (18/21 = 86%) than in the non-apocrine type (14/30 = 46%) (P< 0.05). Ki-67 labeling was significantly higher in the non-apocrine type (58%) than in the apocrine type (37%) (P< 0.01). Epidermal growth factor receptor is consistently expressed in triple-negative breast cancers (16/16 = 100% in apocrine and 18/20 = 90% in non-apocrine).

CONCLUSIONS: Androgen receptor should be added to immunohistochemical panels, since apocrine-type invasive ductal carcinoma, resembling basal-like phenotypes, may show clinical behaviors different from the basal-like triple-negative breast cancer.}, } @article {pmid22446359, year = {2012}, author = {Yang, H and Liu, H and Peng, W and Hua, Y}, title = {Magnetic resonance imaging of the breast in evaluating residual diseases at lumpectomy site soon after excisional biopsy.}, journal = {Journal of computer assisted tomography}, volume = {36}, number = {2}, pages = {196-199}, doi = {10.1097/RCT.0b013e31824afc21}, pmid = {22446359}, issn = {1532-3145}, mesh = {Adult ; Biopsy ; Breast Neoplasms/*pathology/*surgery ; Chi-Square Distribution ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental ; Middle Aged ; Neoplasm, Residual/*diagnosis/pathology/*surgery ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) in the detection of residual disease for patients after excisional biopsy of breast carcinoma, before re-excision.

MATERIALS AND METHODS: We performed a retrospective review of 97 patients who underwent MRI soon after excisional biopsy of breast carcinoma with undeterminable margin status before further surgical intervention to determine the value of MRI in detecting residual disease.

RESULTS: The positive predictive value was 50.0%. The negative predictive value was 78.9%. The MRI detected 54.5% of the residual disease for invasive ductal carcinoma and 100% for ductal carcinoma in situ. Positive predictive value and sensitivity for MRI conducted within 14 days of the original surgery were lower than those for MRI conducted after 14 days of the original surgery, being 31.6% and 46.2% versus 66.7% and 73.4%, respectively. The difference between the positive predictive value within 14 days versus after 14 days was statistically significant.

CONCLUSION: Magnetic resonance imaging in detecting residual disease soon after excisional biopsy for breast carcinoma had a low positive predictive value and moderately high negative predictive value. Magnetic resonance imaging was more sensitive in detecting residual ductal carcinoma in situ than invasive ductal carcinoma. Magnetic resonance imaging conducted more than 14 days after the original biopsy had a significantly higher positive predictive value than MRI done within 14 days.}, } @article {pmid22439598, year = {2012}, author = {Wang, CC and Liau, JY and Lu, YS and Chen, JW and Yao, YT and Lien, HC}, title = {Differential expression of moesin in breast cancers and its implication in epithelial-mesenchymal transition.}, journal = {Histopathology}, volume = {61}, number = {1}, pages = {78-87}, doi = {10.1111/j.1365-2559.2012.04204.x}, pmid = {22439598}, issn = {1365-2559}, mesh = {Adenocarcinoma/*metabolism/mortality/secondary ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Combined Modality Therapy ; Disease Progression ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry/methods ; Microfilament Proteins/*metabolism ; Prognosis ; Survival Rate ; Taiwan/epidemiology ; Tissue Array Analysis ; }, abstract = {AIMS: Moesin belongs to the ERM (ezrin, radixin and moesin) family. Recent in-vitro studies have shown the possible involvement of moesin in epithelial-mesenchymal transition (EMT), but correlating in-vivo evidence is lacking.

METHODS AND RESULTS: To study the biological significance of moesin, we used immunohistochemistry to investigate the in-situ expression profiles of moesin in 322 breast carcinomas of different subtypes, including 23 cases of metaplastic carcinoma (MCB) which is pathogenetically considered to involve EMT. Moesin was highly expressed in 95.7% of cases of MCB, and in 16% of cases of invasive ductal carcinoma (IDC), but was negative in all other subtypes of breast carcinomas. In IDCs, moesin expression correlated positively with a high histological grade (P < 0.001), basal-like phenotype (P < 0.001) and poor overall survival (P = 0.0263). Transfection of MCF7 cells with Snail, one of the key regulators of EMT, showed up-regulation of moesin at the transcriptional level. Finally, mRNA level of moesin correlated positively with Snail and EMT-related genes in a microarray data set using primary breast cancer samples.

CONCLUSION: These results offer biological evidence of moesin as an EMT marker, support the association between moesin, Snail and EMT and suggest a role for moesin in breast cancer prognostication.}, } @article {pmid22438362, year = {2012}, author = {Zhou, W and Zha, X and Liu, X and Ding, Q and Chen, L and Ni, Y and Zhang, Y and Xu, Y and Chen, L and Zhao, Y and Wang, S}, title = {US-guided percutaneous microwave coagulation of small breast cancers: a clinical study.}, journal = {Radiology}, volume = {263}, number = {2}, pages = {364-373}, doi = {10.1148/radiol.12111901}, pmid = {22438362}, issn = {1527-1315}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology/*surgery ; Catheter Ablation/*methods ; Confidence Intervals ; Feasibility Studies ; Female ; Humans ; Mastectomy ; Microwaves/*therapeutic use ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Ultrasonography, Interventional/*methods ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: To determine the feasibility of percutaneous microwave coagulation (PMC) for the treatment of small solitary breast cancers.

MATERIALS AND METHODS: With approval of the institutional ethics committee and written informed consent, 41 patients with core-needle-biopsy-proved breast cancers 3.0 cm or less in diameter accessed by using ultrasonography (US) were recruited. US-guided PMC was performed with general anesthesia, followed immediately by mastectomy. Histochemical staining with α-nicotinamide adenine dinucleotide, reduced (NADH)-diaphorase was used to determine cell viability and the extent of PMC lesions.

RESULTS: The mean tumor volume was 5.26 cm(3) ± 3.80 (standard deviation), with a range from 0.09 to 14.14 cm(3). PMC was successfully performed in all cases, with complete tumor ablation as assessed by using US. The mean time to reach complete ablation was 4.48 minutes, ranging from 3 to 10 minutes. With microscopic examination, 37 of 41 cases (90%; 95% confidence interval [CI]: 76.9%, 97.3%) showed complete tumor coagulation, as observed by using α-NADH-diaphorase staining. Of 38 cases diagnosed with invasive ductal carcinoma, 36 cases (95%; 95% CI: 82.3%, 99.4%) showed complete tumor coagulation. Slight thermal injuries to the skin and pectoralis major muscle, which proved reversible, were found in three cases.

CONCLUSION: US-guided PMC of small solitary breast cancers is feasible. Nevertheless, larger-scale clinical trials are still needed to validate PMC for adoption into a standard clinical practice.}, } @article {pmid22430597, year = {2012}, author = {Ugiagbe, EE and Obaseki, DE and Oluwasola, AO and Olu-Eddo, AN and Akhiwu, WO}, title = {Frequency of distribution of oestrogen and progesterone receptors positivities in breast cancer cases in Benin-City, Nigeria.}, journal = {The Nigerian postgraduate medical journal}, volume = {19}, number = {1}, pages = {19-24}, pmid = {22430597}, issn = {1117-1936}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Breast Neoplasms, Male/epidemiology/metabolism/pathology ; Carcinoma/*metabolism/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Nigeria/epidemiology ; Prognosis ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {AIMS AND OBJECTIVES: The aim of this study is to determine the prevalence of oestrogen and progesterone receptors positivities among histologically diagnosed breast cancer cases at the University of Benin Teaching Hospital, Benin City, Nigeria.

MATERIALS AND METHODS: Cases of breast carcinomas in the records of the Department of Histopathology, University of Benin Teaching Hospital, between 2003 and 2007 constitute the materials used for this study. Immunohistochemical staining was done using representative paraffin-embedded blocks (H&E slides assessment) and stained with oestrogen and progesterone antibodies manufactured by Dako Denmark (AS Denmark).

RESULTS: A total of 135 cases were studied. The female to male ratio was 44:1 with an overall mean age of 48.3±13 years. Invasive ductal carcinoma, NOS (not otherwise specified) was the most common histological type (81.5%). Eighty per cent of cases were categorised as grades 2 and 3 tumours. The steroid hormone receptor positivity was 17%. Oestrogen and Progesterone receptor positivity were 14.1% and 9.6% respectively. There was a statistically significant association between hormone receptor status and the grade of tumour (?2 = 6.37, df = 2, p = 0.04).

CONCLUSION: This study shows a relatively low steroid hormone receptor positivity of breast cancer in Benin. This finding portends a poor prognostic effect and it is consequently recommended that steroid hormone receptor status be determined before hormonal treatment in these patients. There is the need to determine the immunohistochemical patterns of breast cancer in other centres that treat breast cancer patients.}, } @article {pmid22424944, year = {2012}, author = {Chen, YH and Huang, CH}, title = {Reversible posterior leukoencephalopathy syndrome induced by vinorelbine.}, journal = {Clinical breast cancer}, volume = {12}, number = {3}, pages = {222-225}, doi = {10.1016/j.clbc.2012.01.006}, pmid = {22424944}, issn = {1938-0666}, mesh = {Adult ; Antineoplastic Agents/adverse effects/therapeutic use ; Breast Neoplasms/drug therapy ; Carcinoma, Ductal, Breast/drug therapy ; Female ; Humans ; Posterior Leukoencephalopathy Syndrome/*chemically induced/diagnosis ; Vinblastine/adverse effects/*analogs & derivatives/therapeutic use ; Vinorelbine ; }, abstract = {Reversible posterior leukoencephalopathy syndrome (RPLS) was first described in 1996; clinical symptoms include the presence of headache, visual disturbance,seizure, hypertension, and encephalopathy. The syndrome is most commonly encountered in association with chemotherapeutic agents or targeted therapy. Many chemotherapeutic agents, such as cisplatin,gemcitabine, methotrexate, were reported to be associated with RPLS. Vinorelbine is commonly used for the treatment of metastatic breast cancer, but vinorelbine-induced RPLS has not been reported. We reported a 34-year-old woman, diagnosed with invasive ductal carcinoma of the left breast, who experienced acute hypertension after vinorelbine intravenous infusion. Accompanied symptoms included headache,seizure, and conscious disturbance. Magnetic resonance imaging of the brain showed symmetric signal hyperintensity with the cortical and subcortical white matter of bilateral frontal, parietal, and occipital (predominant) lobes. Vinorelbine is a semisynthetic vinca alkaloid and prevents cell division by inhibiting tubulin polymerization.Brain metastasis or leptomeningeal carcinomatosis is an important issue for patients with breast cancer who present with headache, seizure, or altered consciousness.However, now RPLS may be a new consideration,especially with the presentation of acute hypertension. Unlike brain or meningeal metastasis, RPLS is usually benign, and most patients recover within 2 weeks. Our case highlights an association between vinorelbine and RPLS, and the drug has not been described as a predisposing factor of RPLS in past reports. In the era of cancer treatment with chemotherapy or targeted therapy,clinicians should be aware of this syndrome.}, } @article {pmid22423247, year = {2012}, author = {Stebel, A}, title = {Reduction in Circulating Tumor Cell Count following Therapy with nab-Paclitaxel plus Carboplatin in a Patient with Leptomeningeal Carcinomatosis from Breast Cancer.}, journal = {Case reports in oncology}, volume = {5}, number = {1}, pages = {56-61}, pmid = {22423247}, issn = {1662-6575}, abstract = {This case study reports on a 56-year-old woman with breast adenocarcinoma and leptomeningeal metastases. After initial chemotherapy with a dose-dense regimen of doxorubicin/cyclophosphamide followed by 3 cycles of docetaxel (100 mg/m(2)), a lumpectomy was performed that revealed invasive ductal carcinoma with lymph node involvement. Because of the extent of the disease, she underwent a mastectomy. Two months after the completion of initial chemotherapy, leptomeningeal metastases were detected on December 13, 2006. After completion of whole-brain radiation therapy, she received systemic chemotherapy with a novel albumin-bound 130-nm formulation of paclitaxel (nab®-paclitaxel) at 100 mg/m(2) combined with carboplatin AUC = 6, both given weekly. Clinical response was prompt, with a reduction in the circulating tumor cell (CTC) count from 63 before treatment to 2 after the first treatment cycle. While undergoing treatment with nab-paclitaxel plus carboplatin, she reported an improvement in neurologic symptoms, including a decrease in headaches, improved cognition and balance, and an overall improved quality of life. Before the third treatment cycle, she had a CTC count of 2. Without treatment, the median survival of patients diagnosed with leptomeningeal metastases is 4-6 weeks. However, this patient survived for 4 months after the diagnosis of leptomeningeal carcinomatosis. Treatment was discontinued because of complications of urosepsis, and the patient died on April 7, 2007. Our case shows that additional treatment with weekly nab-paclitaxel combined with carboplatin (AUC6) can prolong life for some patients with leptomeningeal carcinomatosis from breast cancer.}, } @article {pmid22419898, year = {2011}, author = {Liu, T and Tong, Z and He, L and Zhang, L}, title = {Clinicopathological Characteristics and Survival Analysis of 87 Male Breast Cancer Cases.}, journal = {Breast care (Basel, Switzerland)}, volume = {6}, number = {6}, pages = {446-451}, pmid = {22419898}, issn = {1661-3791}, abstract = {BACKGROUND: The aim of this study was to investigate the clinicopathologic characteristics, therapy methods, and prognosis of male breast cancer. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological characteristics, recurrence or metastasis, and survival information of 87 male breast cancer patients. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. A p value of <0.05 was considered statistically significant. RESULTS: 5-year disease free survival (DFS) and 5-year overall survival (OS) were 66.3 and 77.0%, respectively. Monofactorial analysis showed tumor size, stage, lymph node involvement, and adjuvant chemotherapy to be prognostic factors with regard to 5-year DFS and 5-year OS. Multivariate Cox regression analysis showed tumor size, stage, and adjuvant chemotherapy to be independent prognostic factors with regard to 5-year DFS and 5-year OS. CONCLUSION: Male breast cancer has a lower incidence rate and poor prognosis. Invasive ductal carcinoma is the main pathologic type. Operation-based combined therapy is the standard care for these patients. Tumor size, stage, and adjuvant chemotherapy are independent prognostic factors. More emphasis should be placed on early diagnosis and early therapy, and adjuvant chemotherapy may improve survival.}, } @article {pmid22415745, year = {2012}, author = {Görkem, SB and O'Connell, AM}, title = {Abnormal axillary lymph nodes on negative mammograms: causes other than breast cancer.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {18}, number = {5}, pages = {473-479}, doi = {10.4261/1305-3825.DIR.5491-11.2}, pmid = {22415745}, issn = {1305-3612}, mesh = {Adult ; Axilla ; Biopsy, Needle ; Breast Implants/adverse effects ; Breast Neoplasms/diagnostic imaging/*pathology/secondary ; Calcinosis/complications/diagnostic imaging/pathology ; Connective Tissue Diseases/complications/diagnostic imaging/pathology ; Female ; Hodgkin Disease/complications/pathology ; Humans ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging/*pathology ; Lymphatic Diseases/*etiology/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/pathology ; Prognosis ; Radiography ; Risk Assessment ; Tattooing/adverse effects ; }, abstract = {Enlargement of lymph nodes can be due to a variety of benign and malignant causes. The most common malignant cause is invasive ductal carcinoma, which is usually visualized with mammography. Excluding breast cancer, other causes of abnormal lymph nodes that produce a negative mammogram include lymphoma, metastases from other malignancies, and benign etiologies such as inflammatory processes, infectious diseases, collagen vascular diseases, and miscellaneous causes. In this essay, we described common causes of abnormal axillary lymph nodes on negative mammograms excluding breast cancer.}, } @article {pmid22415226, year = {2012}, author = {Kalles, V and Zografos, GC and Provatopoulou, X and Kalogera, E and Liakou, P and Georgiou, G and Sagkriotis, A and Nonni, A and Gounaris, A}, title = {Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast cancer early diagnosis.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {33}, number = {4}, pages = {1231-1236}, pmid = {22415226}, issn = {1423-0380}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood ; Breast Neoplasms/*blood/*diagnosis ; Carcinoma, Ductal, Breast/blood/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/blood/diagnosis ; Early Detection of Cancer ; Endothelin-1/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Middle Aged ; Prognosis ; Protein Precursors/*blood ; Sensitivity and Specificity ; }, abstract = {Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.}, } @article {pmid22412048, year = {2012}, author = {Lee, H and Jung, SY and Ro, JY and Kwon, Y and Sohn, JH and Park, IH and Lee, KS and Lee, S and Kim, SW and Kang, HS and Ko, KL and Ro, J}, title = {Metaplastic breast cancer: clinicopathological features and its prognosis.}, journal = {Journal of clinical pathology}, volume = {65}, number = {5}, pages = {441-446}, doi = {10.1136/jclinpath-2011-200586}, pmid = {22412048}, issn = {1472-4146}, mesh = {Biomarkers, Tumor/analysis ; Breast/*pathology ; Breast Neoplasms/chemistry/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/drug therapy/mortality/*secondary ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy, Segmental/methods ; Metaplasia ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Republic of Korea/epidemiology ; Survival Rate ; }, abstract = {AIMS: The prognosis of metaplastic breast cancer (MBC) is reportedly worse than that of triple-negative invasive ductal carcinoma (TN-IDC), but the determinants of poor prognosis are not yet known.

METHODS: Patients from two Korean cancer centres were included in this study (67 MBC and 520 TN-IDC). Characteristics of the two disease groups, including clinical parameters, histological features, chemoresponsiveness, disease recurrence and survival estimates, were evaluated.

RESULTS: MBC presented with larger tumours, more frequent distant metastasis and higher histological grade compared with TN-IDC (p<0.001). All but nine patients with MBC had triple-negative disease. Disease-free survival and overall survival (OS) of MBC were worse than TN-IDC (p<0.001). Multivariable analysis of disease-free survival revealed MBC type as an independent prognostic factor (HR 2.53; 95% CI 1.32 to 4.84) along with lymph node metastasis and implementation of breast conserving surgery. For OS, MBC type remained a significant prognostic factor (HR 2.56; 95% CI 1.18 to 5.54). Chemoresponsiveness of MBC and TN-IDC were similar in both neoadjuvant (p=1.000) and advanced disease settings (p=0.508). For a given MBC type, risk factors for disease recurrence included the presence of a squamous component (HR 4.0; 95% CI 1.46 to 10.99) and lymph node metastasis (HR 4.76; 95% CI 1.67 to 13.60); the risk factor for OS was initial distant metastasis (HR 10.77; 95% CI 2.59 to 44.76).

CONCLUSIONS: MBC had worse survival outcomes compared with TN-IDC. Poor prognosis for MBC was likely caused by frequent recurrence with high initial stage and the unique biology of MBC itself.}, } @article {pmid22410125, year = {2012}, author = {Khurana, A and McKean, H and Kim, H and Kim, SH and mcguire, J and Roberts, LR and Goetz, MP and Shridhar, V}, title = {Silencing of HSulf-2 expression in MCF10DCIS.com cells attenuate ductal carcinoma in situ progression to invasive ductal carcinoma in vivo.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {2}, pages = {R43}, pmid = {22410125}, issn = {1465-542X}, support = {CA106954-04/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Cell Line, Tumor ; Disease Progression ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mammary Neoplasms, Experimental/genetics/pathology ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Nude ; Sulfatases ; Sulfotransferases/*genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of proliferative cellular lesions that have the potential to become invasive. Very little is known about the molecular alterations involved in the progression from DCIS to invasive ductal carcinoma (IDC). Heparan endosulfatase (HSulf-2) edits sulfate moieties on heparan sulfate proteoglycans (HSPGs) and has been implicated in modulating heparin binding growth factor signaling, angiogenesis and tumorigenesis. However, the role of HSulf-2 in breast cancer progression is poorly understood. MCF10DCIS.com cells (referred as MCF10DCIS) express HSulf-2 and form comedo type DCIS and progress to IDC when transplanted in immune-deficient mice and, therefore, is an ideal model to study breast cancer progression. We evaluated the role of HSulf-2 in progression from DCIS to IDC using mouse fat pad mammary xenografts.

METHODS: Non-target control (NTC) and HSulf-2 knockdown in MCF10DCIS breast cancer cells were achieved by NTC shRNA and two different lentiviral shRNA against HSulf-2 respectively. Xenografts were established by injecting NTC and HSulf-2 deficient MCF10DCIS cells in mouse mammary fat pads. Xenografts were subjected to H&E staining for morphological analysis, TUNEL and Propidium iodide staining (to determine the extent of apoptosis), Western blot analysis and zymography.

RESULTS: Using a mouse mammary fat pad derived xenograft model, we observed that compared to control treated xenografts, down-regulation of HSulf-2 was associated with significant delays in growth at Week 7 (P-value < 0.05). Histological examination of the tumors demonstrated substantial differences in comedo necrosis, with marked luminal apoptosis and up-regulation of apoptotic markers Bim, cleaved PARP and cleaved caspase 3 in HSulf-2 depleted xenografts. Furthermore, HSulf-2 depleted xenografts retained the basement membrane integrity with decreased activity and expression of matrix metalloproteinase 9 (MMP-9), an enzyme critical for degradation of extracellular matrix compared to nontargeted control.

CONCLUSION: Our data suggest that HSulf-2 expression may be critical for human breast cancer progression. Down-regulation of HSulf-2 leads to retention of comedo type DCIS and delays the progression of DCIS to IDC. Further studies are necessary to determine if therapeutic targeting of HSulf-2 expression might delay the progression of DCIS to IDC.}, } @article {pmid22405699, year = {2012}, author = {Van der Kwast, T and Al Daoud, N and Collette, L and Sykes, J and Thoms, J and Milosevic, M and Bristow, RG and Van Tienhoven, G and Warde, P and Mirimanoff, RO and Bolla, M}, title = {Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {48}, number = {9}, pages = {1318-1325}, doi = {10.1016/j.ejca.2012.02.003}, pmid = {22405699}, issn = {1879-0852}, mesh = {Aged ; Aged, 80 and over ; Biopsy/methods ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/*pathology/radiotherapy/surgery ; Cohort Studies ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*pathology/radiotherapy/surgery ; Risk Factors ; Treatment Outcome ; }, abstract = {AIM: We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in biopsies and transurethral resections prior to external beam radiotherapy with or without androgen deprivation.

METHODS: Cohort 1 consisted of 118 intermediate risk prostate cancer patients treated by radiotherapy, with biochemical relapse as primary end-point (median follow-up 6.5 years). Cohort 2 consisted of 132 high risk patients, enrolled in a phase III randomised trial (EORTC 22863) comparing radiotherapy alone to radiotherapy with long-term androgen deprivation (LTAD) with clinical progression free survival as primary end-point (median follow-up 9.1 years). Presence of IDC-P was identified after central review. Multivariable regression modelling and Kaplan-Meier analysis were performed with IDC-P as dichotomous variable.

RESULTS: IDC-P was a strong prognosticator for early (<36 months) biochemical relapse (HR 7.3; p = 0.007) in cohort 1 and for clinical disease-free survival in both arms of cohort 2 (radiotherapy arm: HR 3.5; p < 0.0001; radiotherapy plus LTAD arm: HR 2.8, p = 0.018). IDC-P retained significance after stratification for reviewed Gleason score in the radiotherapy arm (HR 2.3; p = 0.03). IDC-P was a strong prognosticator for metastatic failure rate (radiotherapy arm: HR 5.3; p < 0.0001; radiotherapy plus LTAD arm: HR 3.6; p = 0.05).

CONCLUSIONS: IDC-P in diagnostic samples of patients with intermediate or high risk prostate cancer is an independent prognosticator of early biochemical relapse and metastatic failure rate after radiotherapy. We suggest that the presence of IDC-P in prostate biopsies should routinely be reported.}, } @article {pmid22404125, year = {2012}, author = {Oda, M and Makita, M and Iwaya, K and Akiyama, F and Kohno, N and Tsuchiya, B and Iwase, T and Matsubara, O}, title = {High levels of DJ-1 protein in nipple fluid of patients with breast cancer.}, journal = {Cancer science}, volume = {103}, number = {6}, pages = {1172-1176}, pmid = {22404125}, issn = {1349-7006}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*diagnosis/*metabolism/pathology ; Carcinoembryonic Antigen/analysis ; Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/*analysis/*metabolism ; Middle Aged ; Nipple Aspirate Fluid/*chemistry ; Nipples/pathology ; Oncogene Proteins/*analysis/*metabolism ; Protein Deglycase DJ-1 ; }, abstract = {As we have previously demonstrated that some breast cancer cell lines secrete DJ-1 protein, we examined here whether breast cancer cells secrete DJ-1 protein in vivo. To this end, the levels of DJ-1 protein present in 136 specimens of nipple fluid was examined by enzyme-linked immunosorbent assay (ELISA). The average concentration of DJ-1 protein detected in diluted samples from 47 patients with invasive ductal carcinoma (IDC) was 22.4 ng/mL, while it was 18.6 ng/mL in 26 patients with ductal carcinoma in situ (DCIS). In contrast, the average DJ-1 concentration in samples from 63 women with benign lesions was 2.7 ng/mL, demonstrating that higher DJ-1 protein levels were detected in nipple fluid in the presence of cancer cells than in the presence of benign lesions (P < 0.0001). When a cut-off level of 3.0 ng/mL was applied, the higher level of DJ-1 was shown to be of significant clinical value for predicting the presence of breast cancer (85.9% specificity, 75% sensitivity; P < 0.0001). Multivariate logistic analysis that included established factors such as nipple discharge cytology, ductoscopic cytology, and carcinoembryonic antigen level further showed that the level of DJ-1 protein alone is of significant value for predicting the presence of breast cancer. Immunohistochemistry and in situ hybridization also showed that the low expression of DJ-1 protein, despite high mRNA expression, was significantly correlated with high DJ-1 protein levels in the nipple fluid. These data indicate that breast cancer cells secrete DJ-1 protein in vivo, and that its level is a potential indicator of breast cancer in patients with nipple discharge.}, } @article {pmid22400527, year = {2012}, author = {Knufinke, M and Ilin, K and Siegel, M and Koelle, D and Kleiner, R and Goldobin, E}, title = {Deterministic Josephson vortex ratchet with a load.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {85}, number = {1 Pt 1}, pages = {011122}, doi = {10.1103/PhysRevE.85.011122}, pmid = {22400527}, issn = {1550-2376}, mesh = {Computer Simulation ; *Electromagnetic Fields ; Microfluidics/*methods ; *Models, Theoretical ; *Nonlinear Dynamics ; }, abstract = {We investigate experimentally a deterministic underdamped Josephson vortex ratchet-a fluxon particle moving along a Josephson junction in an asymmetric periodic potential. By applying a sinusoidal driving current, one can compel the vortex to move in a certain direction, producing an average dc voltage across the junction. Being in such a rectification regime, we also load the ratchet, i.e., apply an additional dc bias current I(dc) (counterforce) which tilts the potential so that the fluxon climbs uphill due to the ratchet effect. The value of the bias current at which the fluxon stops climbing up defines the strength of the ratchet effect and is determined experimentally. This allows us to estimate the loading capability of the ratchet, the output power, and the efficiency. For the quasistatic regime we present a simple model which delivers straightforward analytic expressions for the above-mentioned figures of merit.}, } @article {pmid22399591, year = {2012}, author = {Kobierzycki, C and Pula, B and Wojnar, A and Podhorska-Okolow, M and Dziegiel, P}, title = {Tissue microarray technique in evaluation of proliferative activity in invasive ductal breast cancer.}, journal = {Anticancer research}, volume = {32}, number = {3}, pages = {773-777}, pmid = {22399591}, issn = {1791-7530}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Cell Proliferation ; Immunohistochemistry ; *Neoplasm Invasiveness ; Paraffin Embedding ; Tissue Array Analysis/*methods ; }, abstract = {AIM: Investigation of the relationship between expression of Ki-67 antigen and minichromosome maintenance 2 (MCM-2) protein by using an immunohistochemical study on whole sections (WS) and sections of invasive ductal breast cancer (IDC) obtained in the tissue microarray (TMA) technique.

MATERIALS AND METHODS: Material consisted of 51 archival paraffin blocks of IDC. Tissue microarrays were composed of 0.6 mm core punches. Reactions were performed using specific antibodies (anti-Ki-67 and anti-MCM-2). Intensity of the marker expression was evaluated using computer-assisted image analysis. For statistical purposes, three different tests were used.

RESULTS: Spearman rank correlation revealed a strong positive correlation between expression of tested markers: Ki-67 (TMA) vs. Ki-67 (WS) (r=0.91, p<0.05) and MCM-2 (TMA) vs. MCM-2 (WS) (r=0.87, p<0.05). Mann Whitney U-test showed no significant differences between the two markers in both analysed techniques. Moreover, the Bland-Altman plot demonstrated a low level of bias between the analysed methods.

CONCLUSION: This study shows that TMA could have a great potential in evaluation of proliferative activity in IDC and that MCM-2 protein might be a specific and sensitive marker of cell proliferation.}, } @article {pmid22396001, year = {2012}, author = {Seki, H and Hayashida, T and Jinno, H and Hirose, S and Sakata, M and Takahashi, M and Maheswaran, S and Mukai, M and Kitagawa, Y}, title = {HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients.}, journal = {Annals of surgical oncology}, volume = {19}, number = {6}, pages = {1831-1840}, doi = {10.1245/s10434-012-2295-5}, pmid = {22396001}, issn = {1534-4681}, mesh = {Adenocarcinoma/blood supply/metabolism/mortality/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/mortality/pathology ; *Cell Proliferation ; Female ; Homeodomain Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; *Neovascularization, Pathologic ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Studies have suggested that HOXB9 expression in breast cancer cells promotes cellular invasiveness, metastatic ability, and tumor neovascularization in the surrounding tissue in in vitro and in vivo assays. These findings imply that HOXB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to breast cancer progression. The objective of this study was to analyze whether these results could be applied to clinical practice.

METHODS: A total of 141 consecutive, invasive ductal carcinoma patients who underwent surgical treatment were examined. Immunohistochemical staining was performed to evaluate the expression of HOXB9, Ki-67, CD31, and CD34, and the association of tumor proliferation and angiogenesis with HOXB9 expression was analyzed.

RESULTS: Of the 141 tumor specimens immunostained for HOXB9, 69 (48.9%) stained positive. Larger primary tumor size, hormone receptor negativity, HER2 positivity, higher nuclear grade, and number of pathologic nodal metastases were significant variables associated with HOXB9 expression. Notably, 12 (92.3%) of 13 triple-negative breast cancer cases showed HOXB9 expression. Disease-free survival and overall survival were significantly different between the HOXB9-positive and HOXB9-negative groups (hazard ratio 20.714, P = 0.001; and hazard ratio 9.206, P = 0.003, respectively). Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for disease-free survival (hazard ratio 15.532, P = 0.009). HOXB9-positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio compared with HOXB9-negative tumors.

CONCLUSIONS: HOXB9 expression, which promotes tumor proliferation and angiogenesis, is a significant prognostic factor in breast cancer.}, } @article {pmid22393683, year = {2011}, author = {Pusiol, T and Morichetti, D and Zorzi, MG}, title = {Oncocytic carcinoma of the parotid gland: case report and review of the literature.}, journal = {Pathologica}, volume = {103}, number = {5}, pages = {279-289}, pmid = {22393683}, issn = {0031-2983}, mesh = {Adenocarcinoma/*pathology/surgery ; Axilla ; Breast Neoplasms, Male/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis ; Male ; Mastectomy ; Middle Aged ; *Neoplasms, Multiple Primary ; Oxyphil Cells/*pathology ; Parotid Neoplasms/*pathology/surgery ; }, abstract = {OBJECTIVES: To date 70 cases of oncocytic carcinomas (OCs) have been described in 55 reports. We describe an OC of the parotid gland in a 56-year-old man with simultaneous breast cancer.

METHODS: In June 2006, a 56-year-old man was referred to the Otorhinolaryngology Division for a painless right preauricolar mass. The facial nerve was functionally normal. Total parotidectomy with facial nerve preservation was performed. In January 2007, the patient was referred to the Surgical Division for a left mammary nodule. Total mastectomy with axillary lymphoadenectomy was performed.

RESULTS: The mass of the parotid gland measured 3.5 x 3 cm. Histology showed sheets, islands and nests composed of large, round to polyhedral cells with fine, granular, eosinophilic cytoplasm and round vesicular nuclei, with prominent nucleoli. The tumour cells were positive for immunohistochemical staining with antimitochondria antibodies. Histological examination of the mammary tumour showed invasive ductal carcinoma Grade III (Nottingham Histologic Score) with metastasis in 12 axillary lymph nodes. Chemotherapy was performed. At present, the patient is free of recurrences or metastases.

CONCLUSIONS: Histologically, there is a spectrum of malignant parotid gland neoplasms that have prominent eosinophilic granular cytoplasm due to increased number of mitochondria. OCs have cytoplasm packed with mitochondria, while the term "oncocytoid" should be employed for tumours that have abundant eosinophilic granular cytoplasm, but ultrastructurally do not possess marked mitochondrial hyperplasia. All reported cases of OC should be defined "oncocytic-like carcinoma" when only haematoxylin and eosin staining is performed.}, } @article {pmid22385318, year = {2012}, author = {Tsuchiya, B and Iwaya, K and Kohno, N and Kawate, T and Akahoshi, T and Matsubara, O and Mukai, K}, title = {Clinical significance of DJ-1 as a secretory molecule: retrospective study of DJ-1 expression at mRNA and protein levels in ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {61}, number = {1}, pages = {69-77}, doi = {10.1111/j.1365-2559.2012.04202.x}, pmid = {22385318}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/pathology/surgery ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; *Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Japan/epidemiology ; Kaplan-Meier Estimate ; Ki-67 Antigen/metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Staging ; *Oncogene Proteins/genetics/metabolism ; Prognosis ; Protein Deglycase DJ-1 ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Tissue Array Analysis ; Young Adult ; }, abstract = {AIMS: DJ-1 is a molecule secreted into serum by some breast cancer cells. However, little is known about the clinical significance of the DJ-1 expression.

METHODS AND RESULTS: Expression of DJ-1 protein was examined by immunohistochemistry, and expression of DJ-1 mRNA was detected using in-situ hybridization in 273 invasive ductal carcinomas (IDCs) and 41 ductal carcinomas in situ (DCISs) of the breast, and also in breast cancer cell lines. Breast cancer cells were examined for their secretion of DJ-1 using immunoblot analysis. By immunohistochemistry DJ-1 protein expression was lower than adjacent non-cancerous epithelium in 6 (14.6%) of the 41 DCISs and 146 (53%) of the 273 IDCs, even although all 314 carcinomas retained expression of DJ-1 mRNA, which was higher than that in adjacent non-cancerous epithelium in 220 cases (70%). Patients with IDC whose cancer cells showed low expression of DJ-1 protein had significantly shorter disease-free survival (P = 0.0152) and overall survival (P = 0.0196) than those whose cancer cells retained DJ-1 expression. MDA-MB-231 cells, which secreted DJ-1, showed low expression of DJ-1 protein.

CONCLUSIONS: Low expression of DJ-1 protein with high expression of its mRNA, which may reflect a secretory expression pattern, is predictive of poor outcome in patients with IDC.}, } @article {pmid22382854, year = {2012}, author = {Zaha, H and Onomura, M and Nishikuramori, Y}, title = {Pyogenic vertebral osteomyelitis in a breast cancer patient: report of a case.}, journal = {Surgery today}, volume = {42}, number = {10}, pages = {1022-1025}, pmid = {22382854}, issn = {1436-2813}, mesh = {Aged ; Breast Neoplasms/complications/*diagnosis ; Carcinoma, Ductal, Breast/complications/*diagnosis/secondary ; *Cervical Vertebrae ; Diagnosis, Differential ; Escherichia coli Infections/complications/*diagnosis ; Female ; Humans ; Osteomyelitis/complications/*diagnosis ; Spinal Neoplasms/*diagnosis/secondary ; *Thoracic Vertebrae ; }, abstract = {We herein report a rare case of pyogenic vertebral osteomyelitis (PVO) coexisting with breast carcinoma. A 71-year-old female presented with neck pain without fever. Magnetic resonance imaging (MRI) showed suspected metastatic lesions in her neck (C7 and Th1). Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the neck spines and in the left breast. A core needle biopsy of the left breast revealed the presence of invasive ductal carcinoma. Our first tentative diagnosis of the patient was left breast carcinoma with bone metastases, and first-line endocrine therapy was started. However, surgical intervention for the spines had to be considered, because her neurological symptoms progressed. A repeated MRI scan showed a narrowing of the disc space and fluid accumulation around the vertebrae. This suggested the presence of PVO rather than metastases. Surgery confirmed the presence of PVO in C7 and Th1, and a culture of the abscess yielded Escherichia coli. The patient's neurological symptoms dramatically improved after surgery. Breast conserving surgery was performed 3 months after the surgery for PVO. The patient is well and has no clinical evidence of disease 18 months after the breast conserving surgery. PVO is rare, but should be included in the differential diagnosis in patients presenting with early breast carcinoma.}, } @article {pmid22382823, year = {2012}, author = {Robinson, JO and Pozzi-Langhi, S and Phillips, M and Pearson, JC and Christiansen, KJ and Coombs, GW and Murray, RJ}, title = {Formal infectious diseases consultation is associated with decreased mortality in Staphylococcus aureus bacteraemia.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {31}, number = {9}, pages = {2421-2428}, pmid = {22382823}, issn = {1435-4373}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage ; Bacteremia/*diagnosis/drug therapy/*mortality ; Child ; Critical Care/statistics & numerical data ; Endocarditis, Bacterial/epidemiology ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Referral and Consultation/*statistics & numerical data ; Retrospective Studies ; Staphylococcal Infections/*diagnosis/drug therapy/*mortality ; Staphylococcus aureus/*isolation & purification ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {To determine the impact of infectious diseases consultation (IDC) in Staphylococcus aureus bacteraemia. All MRSA bacteraemia and a random subset of MSSA bacteraemia were retrospectively analysed. Out of 599 SAB episodes, 162 (27%) were followed by an IDC. Patients with IDC were younger and more frequently intravenous drug users, but fewer resided in a long-term care facility or were indigenous. Hospital length of stay was longer (29.5 vs 17 days, p < 0.001), and endocarditis (19.1% vs 7.3%, p < 0.001) and metastatic seeding (22.2% vs 10.1%, p < 0.001) were more frequent in the IDC group; however, SAPS II scores were lower in the IDC group (27 vs 37, p < 0.001). ICU admission rates in the two groups were similar. The isolate tested susceptible to empirical therapy more frequently in the IDC group (88.9% vs 78.0%, p = 0.003). Seven-day (3.1 vs 16.5%), 30-day (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC group (all p < 0.001). Multivariate analysis showed that effective initial therapy was the only variable associated with the protective effect of IDC. In patients with SAB, all-cause mortality was significantly lower in patients who had an IDC, because of the higher proportion of patients receiving effective initial antibiotics.}, } @article {pmid22377956, year = {2012}, author = {Zheng, S and Bai, JQ and Li, J and Fan, JH and Pang, Y and Song, QK and Huang, R and Yang, HJ and Xu, F and Lu, N and Qiao, YL}, title = {The pathologic characteristics of breast cancer in China and its shift during 1999-2008: a national-wide multicenter cross-sectional image over 10 years.}, journal = {International journal of cancer}, volume = {131}, number = {11}, pages = {2622-2631}, doi = {10.1002/ijc.27513}, pmid = {22377956}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/metabolism/*pathology ; China/epidemiology ; Cross-Sectional Studies ; Diagnostic Imaging/methods ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Young Adult ; }, abstract = {In China, breast cancer is currently the most common malignancy and the sixth leading cause of cancer death in women. But, the characteristics of breast cancer in the whole population are not determined. The aim of this study was to perform a detailed study on pathologic characteristics of breast cancer representing the whole population in China during 1999-2008 and to compare the difference in invasive breast cancer between the Western and Chinese. We randomly collected 4,211 inpatient at seven hospitals in representative geographical regions of China during 1999-2008. All the hospitals had the ability of comprehensive cancer treatment. The pathologic characters including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were surveyed. The shift of pathologic characters was evaluated and the data from China were also compared with those of the Western, both using Chi-square test. We found as follow. (i) The median age of the patients was 48 years and showed the similar characters of Asia. (ii) Breast cancer in China showed more invasive ductal carcinoma with larger tumor size, later stage, lower ER and PR expression and higher HER2 overexpression than those in the Western (p < 0.001). (iii) Both tumor size and stage at diagnosis decreased year by year (p < 0.001). Breast cancer in China showed more aggressive behavior than those in western countries, although tumor size and stage at diagnosis decreased by year during 1999-2008. We addressed the urgent needs for employ race-specific breast cancer screen, diagnosis methods, and therapeutic models in China.}, } @article {pmid22377278, year = {2012}, author = {El-Zaemey, S and Nagi, N and Fritschi, L and Heyworth, J}, title = {Breast cancer among Yemeni women using the National Oncology Centre Registry 2004-2010.}, journal = {Cancer epidemiology}, volume = {36}, number = {3}, pages = {249-253}, doi = {10.1016/j.canep.2012.01.006}, pmid = {22377278}, issn = {1877-783X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology ; Early Detection of Cancer/*methods ; Female ; *Health Services Accessibility ; Humans ; Lymphatic Metastasis ; Middle Aged ; Registries ; Yemen/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: In developing countries including Arab countries breast cancer is one of the most common cancers found in women. Even though breast cancer incidence is lower in Arab developing countries than in western countries, Arabic women are more likely to be diagnosed at an earlier age than the women in western countries.

METHOD: A descriptive study was undertaken to investigate the type of breast cancer, lymph node involvement, side of breast and, region and age distribution of breast cancer patients registered in the National Oncology Centre in Yemen.

RESULTS: From September 2004 to December 2010, 2654 women across Yemen diagnosed with breast cancer were registered in the National Oncology Centre for treatment. Between the years 2004 and 2010, breast cancer represented 22% of all cancers registered in women. Seventy-one per cent of the women were aged 50 or younger at the time of diagnosis. The most common age group affected was women aged 41-50 years, with (35%) of cases occurring in this age. Invasive ductal carcinoma was the most common pathology (76%) and 79% of the patients had lymph node involvement at the time of diagnosis. Approximately 2% had bilateral disease and the frequency of left (44%) and right breast cancer (42%) were similar.

CONCLUSION: This study has shown that breast cancer is a disease of young women in Yemen. The majority of women presented with lymph node involvement. Hence efforts are needed to increase breast cancer awareness in Yemen for early detection at all age groups, and to target women living in areas that have lower access to health care services.}, } @article {pmid22369445, year = {2012}, author = {Chan, A and Willsher, PC and Hastrich, DJ and Anderson, J and Barham, T and Latham, B and Redfern, A and VAN DER Schaaf, A and Thomson, J and Joseph, D and Ingram, D}, title = {Preoperative taxane-based chemotherapy in a standardized protocol for locally advanced breast cancer.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {8}, number = {1}, pages = {62-70}, doi = {10.1111/j.1743-7563.2011.01489.x}, pmid = {22369445}, issn = {1743-7563}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Carcinoma, Lobular/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Docetaxel ; Doxorubicin/administration & dosage ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm, Residual/*drug therapy/pathology ; Positron-Emission Tomography ; *Preoperative Care ; Quality of Life ; Taxoids/administration & dosage ; Treatment Outcome ; }, abstract = {AIMS: To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) in predicting the extent of residual disease.

METHODS: Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m(2) , doxorubicin 50 mg/m(2) , cyclophosphamide 500 mg/m(2) (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate.

RESULTS: Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol-specified time and 12 (23%) patients had breast conservation surgery. At a median follow-up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease-free survival.

CONCLUSION: This regimen of TAC is effective and well-tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.}, } @article {pmid22366096, year = {2012}, author = {Putignani, L and Raffa, S and Pescosolido, R and Rizza, T and Del Chierico, F and Leone, L and Aimati, L and Signore, F and Carrozzo, R and Callea, F and Torrisi, MR and Grammatico, P}, title = {Preliminary evidences on mitochondrial injury and impaired oxidative metabolism in breast cancer.}, journal = {Mitochondrion}, volume = {12}, number = {3}, pages = {363-369}, doi = {10.1016/j.mito.2012.02.003}, pmid = {22366096}, issn = {1872-8278}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Humans ; Microscopy, Immunoelectron ; Mitochondria/enzymology/*metabolism/*ultrastructure ; Oxidative Phosphorylation ; Oxygen Consumption ; Tumor Cells, Cultured ; }, abstract = {Mitochondriopathy is emerging as a new cancer theory; however, the relevance of mitochondrial pathobiology in breast cancer has not yet been completely explored. Herein we report on altered expression levels of the oxidative phosphorylation system (OXPHOS) subunits, mitochondrial structural injury and impaired ATP content from a breast-infiltrating ductal carcinoma (IDC). With this purpose, a human mammary carcinoma (HMC-1) cell, referred to a human mammary epithelial cell (HMEC) line, was assayed for: a) OXPHOS levels by quantitative cryo-immunoelectron microscopy (CIEM) labeling; b) morphological characterization by a newly introduced damage grading (scale Mt-g1-3), calculated on the % of intact cristae carrying mitochondria; c) bioenergetic impairment by luminometric determinations of cellular ATP content and cytochemical visualization of COX activity. Drastic OXPHOS reduction was observed in HMC-1 cells for the succinate-dehydrogenase complex II SDH-B protein, while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I NDUFS3 and the ubiquinol cytochrome c reductase complex III UQCRC2 subunits. A significant dropping was detected for the ATP-synthase complex V F1β protein. For the COX complex near-depletion of the mitochondrial-encoded COXI and no apparent variation of the COXIV subunits were observed. Injury grading was categorized assigning three levels of morphological damage in HMC-1 mitochondria: i) severe (4.6%), ii) moderate (23.1%), iii) slight (44.6%), corresponding to 0%, 1-50% and 51-75% of area occupied by intact cristae. ATP generation and COX activity appeared significantly reduced in HMC-1 cells. The structural damage grading here described could provide new insight on IDC mitochondrial impairment and represent hallmark in the breast cancer mitochondriopathy.}, } @article {pmid22366088, year = {2012}, author = {Korwar, AM and Bhonsle, HS and Chougale, AD and Kote, SS and Gawai, KR and Ghole, VS and Koppikar, CB and Kulkarni, MJ}, title = {Analysis of AGE modified proteins and RAGE expression in HER2/neu negative invasive ductal carcinoma.}, journal = {Biochemical and biophysical research communications}, volume = {419}, number = {3}, pages = {490-494}, doi = {10.1016/j.bbrc.2012.02.039}, pmid = {22366088}, issn = {1090-2104}, mesh = {Amino Acid Sequence ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Glycation End Products, Advanced/*metabolism ; Humans ; Mitogen-Activated Protein Kinases/*biosynthesis ; Molecular Sequence Data ; NADPH Oxidases/metabolism ; NF-kappa B/metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Protein Processing, Post-Translational ; Receptor for Advanced Glycation End Products/*biosynthesis ; Receptor, ErbB-2/analysis/metabolism ; }, abstract = {Cancer is associated with increased glycolysis and carbonyl stress. In view of this, AGE modified proteins were identified from clinical breast cancer tissue using 2DE-immunoblot and mass-spectrometry. These proteins were identified to be serotransferrin, fibrinogen gamma chain, glycerol-3-phosphate dehydrogenase, lactate dehydrogenase, annexin II, prohibitin and peroxiredoxin 6, which have established role in cancer. Further, RAGE expression and its downstream signaling proteins NADPH oxidase and NF-kB were studied. Role of these AGE modified proteins and RAGE signaling in breast cancer is discussed.}, } @article {pmid22361036, year = {2012}, author = {Yigit, S and Pehlivan, FS and Evcim, G and Etit, D}, title = {Clinicopathologic features of the mixed epithelial and mesenchymal type metaplastic breast carcinoma with myoepithelial differentiation in a subset of six cases.}, journal = {Pathology, research and practice}, volume = {208}, number = {3}, pages = {147-150}, doi = {10.1016/j.prp.2011.12.014}, pmid = {22361036}, issn = {1618-0631}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/*pathology ; Cell Differentiation ; Epithelial Cells/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Complex and Mixed/*metabolism/*pathology ; }, abstract = {Metaplastic carcinoma (MC) of the breast, consisting of epithelial and mixed epithelial-mesenchymal tumors, are extremely rare human neoplasms. They are mostly detected between the 5th and 7th decade and have an unfavorable prognosis. Therefore, it is of utmost important to find out the behavior and also the immunohistochemical (IHC) profile of these tumors. In the current study, the aim was to examine 6 cases of MC with detailed clinico-pathological variables of cancer, follow-up and IHC profile of several antigens. The following immunohistochemical markers were used: MNF116, vimentin, CD10, smooth muscle actin (SMA), estrogen/progesterone receptors and HER-2/neu. The mean age was 39.1 the mean size was 3.3 cm. 83% of the cases had spindle cell sarcoma-like areas. Two of six cases also had a chondrosarcoma-like component. The epithelial component was invasive ductal carcinoma in all. MNF116, vimentin, CD10, and SMA expressions were as follows: mesenchymal cells: 33%, 100%, 50%, 83%, epithelial cells: 100%, 50%, 33%, 0%. All were triple negative. 66.6% presented with the axillary lymph node metastases. The mean follow-up period was 51 months, 50% died of the disease. Two had distant metastases to the lung. Our series which only included mixed epithelial-mesenchymal type metaplastic carcinoma of the breast showed myoepithelial differentiation with a worse prognosis.}, } @article {pmid22360505, year = {2012}, author = {Liu, S and Wang, X and Sun, F and Kong, J and Li, Z and Lin, Z}, title = {DEK overexpression is correlated with the clinical features of breast cancer.}, journal = {Pathology international}, volume = {62}, number = {3}, pages = {176-181}, doi = {10.1111/j.1440-1827.2011.02775.x}, pmid = {22360505}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma in Situ/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Chromosomal Proteins, Non-Histone/*metabolism ; Disease Progression ; Female ; Humans ; Hyperplasia/metabolism/pathology ; Immunohistochemistry ; Neoplasm Staging ; Oncogene Proteins/*metabolism ; Poly-ADP-Ribose Binding Proteins ; Precancerous Conditions/metabolism/pathology ; }, abstract = {To investigate the clinicopathological significance of DEK overexpression in breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of invasive ductal carcinoma of the breast, were selected from the Department of Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK, estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had higher positivity in DCIS, compared with the adjacent normal breast tissues. Also, DEK protein was strongly positive in invasive ductal carcinoma of the breast on immunohistochemistry, which was significantly higher than normal breast tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast showed positive staining for DEK protein. Additionally, DEK overexpression was significantly correlated with the increased proliferating index of Ki-67. For the histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%) compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%) (P<0.05). And DEK protein showed higher expression level in < 3 years disease free survival breast cancers than it did in ≥ 3 years disease free survival cases (P<0.05). However, no statistically difference was found among DEK expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK overexpression appears to be associated with breast cancer progression and DEK may potentially be used as a breast cancer biomarker for the early diagnosis, prognostic evaluation and therapeutic target for breast cancer.}, } @article {pmid22360038, year = {2011}, author = {Shamim, M and Baddar, N}, title = {Axillary ectopic carcinoma of breast.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {61}, number = {9}, pages = {916-918}, pmid = {22360038}, issn = {0030-9982}, mesh = {Aged ; Axilla ; *Breast ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Choristoma/*pathology/surgery ; Female ; Humans ; }, abstract = {Carcinoma in ectopic breast tissue is rare. This is a case report of a 70-year-old postmenopausal female, who presented with a painless mass in right axilla, diagnosed as invasive ductal carcinoma of ectopic breast tissue an excisional biopsy. Postoperatively she was put on tamoxifen, and remained well 10 months after surgery.}, } @article {pmid22359222, year = {2012}, author = {Sanli, Y and Kuyumcu, S and Ozkan, ZG and Işik, G and Karanlik, H and Guzelbey, B and Turkmen, C and Ozel, S and Yavuz, E and Mudun, A}, title = {Increased FDG uptake in breast cancer is associated with prognostic factors.}, journal = {Annals of nuclear medicine}, volume = {26}, number = {4}, pages = {345-350}, doi = {10.1007/s12149-012-0579-2}, pmid = {22359222}, issn = {1864-6433}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biological Transport ; Breast Neoplasms/*diagnosis/diagnostic imaging/*metabolism/pathology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Middle Aged ; Multimodal Imaging ; Neoplasm Staging ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Tomography, X-Ray Computed ; Tumor Burden ; Young Adult ; }, abstract = {PURPOSE: To evaluate the relationship between FDG uptake and prognostic factors of breast cancer such as hormone receptors (estrogen and progesterone), expression of c-erbB-2, axillary lymph node status, tumor histology, grade and size.

MATERIALS AND METHODS: Between May 2009 and February 2011; 79 patients (mean age ± SD: 52.9 ± 13.9 years) with biopsy proven breast cancer underwent F-18 FDG PET/CT scanning for staging. Patients with excisional biopsy or neoadjuvant chemotherapy were excluded from the study. Histological types included were invasive ductal carcinoma (n = 68), invasive lobular carcinoma (n = 2), and invasive ductal plus lobular mixed carcinoma (n = 9). Maximum standardized uptake values (SUVmax) were compared with estrogen (ER) and progesterone receptors (PR), expression of c-erbB-2, as well as tumor grade and tumor size. For the evaluation of relationship between tumor SUVmax values and prognosticators such as hormone receptors, tumor histologic grade, and tumor size, statistical analyses were performed using Student t test, Mann-Whitney U Test and Pearson correlation coefficient and p values of less than 0.05 were considered to indicate statistically significant differences.

RESULTS: All primary breast neoplasms were detected by PET/CT scanner. The mean SUVmax values and breast cancer tumor sizes ranged from 2.09 to 39.0 and 0.7 to 10 cm, respectively. Tumors with negative ER [(n = 19); SUVmax median (min-max): 15 (2.09-39.0)] were associated with higher SUVmax values (p = 0.01). Tumors with overexpression of C-erbB-2 [(n = 28); SUVmax median (min-max): 16.0 (5.0-39.0)]; tumor grade 3 [(n = 25); SUVmax median (min-max): 15 (6.43-39)]; axillary lymph node involvement [(n = 60); SUVmax median (min-max): 13.61 (4.0-39.0)]; tumor histopathology and increased tumor size were associated with higher maximum standardized uptake values. However, PR did not show any relationship with SUVmax values.

CONCLUSION: In the present report, strong relationships were detected between the negativity of ER, overexpression of c-erbB-2, tumor grade, tumor size, histopathology, axillary lymph node involvement and SUVmax values. Accordingly, we believe that SUVmax values obtained with (18)F-FDG PET/CT may provide some information about tumor biology of breast cancer.}, } @article {pmid22358027, year = {2012}, author = {Vilar, VS and Goldman, SM and Ricci, MD and Pincerato, K and Oliveira, H and Abud, TG and Ajzen, S and Baracat, EC and Szejnfeld, J}, title = {Analysis by MRI of residual tumor after radiofrequency ablation for early stage breast cancer.}, journal = {AJR. American journal of roentgenology}, volume = {198}, number = {3}, pages = {W285-91}, doi = {10.2214/AJR.10.5581}, pmid = {22358027}, issn = {1546-3141}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Catheter Ablation/instrumentation/*methods ; Contrast Media ; Electrodes ; Equipment Design ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Meglumine ; Middle Aged ; Neoplasm, Residual/*pathology ; Organometallic Compounds ; Prospective Studies ; Sentinel Lymph Node Biopsy ; Ultrasonography, Interventional ; }, abstract = {OBJECTIVE: The objective of our study was to evaluate the effectiveness of MRI in the detection of possible residual lesions after radiofrequency ablation (RFA) in the treatment of breast cancer.

SUBJECTS AND METHODS: We prospectively evaluated 14 patients who had undergone ultrasound-guided core biopsies diagnostic of invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension and again 3 weeks after RFA to verify the presence of possible residual lesions. Conventional surgical resection of the tumors was performed 1 week after RFA. The MRI findings were compared with histopathologic analyses to confirm the presence or absence of residual tumor.

RESULTS: There was no residual enhancement in seven lesions on the postablation breast MRI scans. These findings were confirmed by negative histopathologic findings in the surgical specimens. The MRI scans of five patients showed small areas of irregular enhancement that corresponded to residual lesions. In the two remaining patients, we observed enhancement of almost the entire lesion, indicating that RFA had failed.

CONCLUSION: Breast MRI is effective in detecting residual lesions after RFA in patients with IDC.}, } @article {pmid22351878, year = {2012}, author = {Moriya, T and Traverso, W}, title = {Fate of the pancreatic remnant after resection for an intraductal papillary mucinous neoplasm: a longitudinal level II cohort study.}, journal = {Archives of surgery (Chicago, Ill. : 1960)}, volume = {147}, number = {6}, pages = {528-534}, doi = {10.1001/archsurg.2011.2276}, pmid = {22351878}, issn = {1538-3644}, mesh = {Adenoma/pathology/surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/pathology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Pancreas/diagnostic imaging/*pathology ; Pancreatectomy ; Pancreatic Neoplasms/diagnostic imaging/pathology/*surgery ; Reoperation ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: To determine the occurrence of new disease in the pancreatic remnant after resection for intraductal papillary mucinous neoplasms.

DESIGN: A longitudinal level II cohort study.

SETTING: Virginia Mason Medical Center, Seattle, Washington.

PATIENTS: The primary cohort was a "resection cohort" of 203 patients who underwent partial pancreatic resection for an intraductal papillary mucinous neoplasm.

MAIN OUTCOME MEASURES: The occurrence rate of lesions in the pancreatic remnant after resection for an intraductal papillary mucinous neoplasm, determined by use of an annual computed tomographic scan of the pancreas.

RESULTS: New lesions were observed in the remnant of 17 of the 203 patients (8%) after a median follow-up of 40 months and a median interval of 38 months from the initial resection. Only 1 of these 17 patients with new lesions had a surgical margin that was positive for an adenoma at the time of resection. Comparing the 17 patients with new lesions with the 186 patients without new lesions, we found no difference in age, sex, procedure type, location in ductal system, original histology, or original margin status. In the new lesion group, no treatment was used for 12 patients who had side-branch disease detected by imaging (6% of all patients). Surgical treatment was used for 5 patients (2% of all patients): 2 with adenomas, 1 with a carcinoma in situ, and 2 with an invasive ductal carcinoma (1 with liver metastases).

CONCLUSIONS: We found that, following a partial pancreatic resection for an intraductal papillary mucinous neoplasm and a 40-month follow-up with an annual computed tomographic scan of the pancreas, 17 of 203 patients (8%) developed a new intraductal papillary mucinous neoplastic lesion in the pancreatic remnant. As follow-up time increases, we suspect that new lesions will constantly appear regardless of whether the surgical margin was negative at initial resection.}, } @article {pmid22347174, year = {2011}, author = {Levit-Binnun, N and Golland, Y}, title = {Finding behavioral and network indicators of brain vulnerability.}, journal = {Frontiers in human neuroscience}, volume = {6}, number = {}, pages = {10}, pmid = {22347174}, issn = {1662-5161}, abstract = {Resilience research has usually focused on identifying protective factors associated with specific stress conditions (e.g., war, trauma) or psychopathologies (e.g., post-traumatic stress disorder [PTSD]). Implicit in this research is the concept that resilience is a global construct, invariant to the unfavorable circumstances or the psychopathologies that may develop (i.e., the mechanisms underlying the resilience of an individual in all cases are expected to be similar). Here we contribute to the understanding of resilience-and its counterpart, vulnerability-by employing an approach that makes use of this invariant quality. We outline two main characteristics that we would expect from indicators of a vulnerable state: that they should appear across disorders regardless of specific circumstances, and that they should appear much before the disorder is evident. Next, we identify two sets of factors that exhibit this pattern of association with psychopathological states. The first was a set of "low-level" sensory, motor and regulatory irregularities that have been reported across the clinical literature; we suggest that these can serve as behavioral indicators of a vulnerable state. The second was the set of aberrations in network metrics that have been reported in the field of systems neuroscience; we suggest that these can serve as network indicators of a vulnerable state. Finally, we explore how behavioral indicators may be related to network indicators and discuss the clinical and research-related implications of our work.}, } @article {pmid22336175, year = {2012}, author = {Bozkurt, KK and Kapucuoğlu, N}, title = {Investigation of immunohistochemical ERα, ERβ and ERβcx expressions in normal and neoplastic breast tissues.}, journal = {Pathology, research and practice}, volume = {208}, number = {3}, pages = {133-139}, doi = {10.1016/j.prp.2011.12.015}, pmid = {22336175}, issn = {1618-0631}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Estrogen Receptor alpha/analysis/*biosynthesis ; Estrogen Receptor beta/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Protein Isoforms/analysis/biosynthesis ; }, abstract = {Estrogen receptor alpha (ERα) is a well-established prognostic marker in breast cancer. The role of estrogen receptor beta (ERβ) in breast cancers is still under investigation. We aimed to investigate the clinicopathological significance and immunohistochemical expression patterns of ERα, total ERβ (ERβ) and its spliced variant ERβcx in normal breast, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our study population comprised 10 normal breasts, 26 DCISs and 44 IDCs. Immunohistochemical expression of these markers was investigated in sections of formalin-fixed, paraffin-embedded blocks by 2 observers. In invasive ductal carcinomas, ERβ expression had a significant positive correlation with ERα expression (p=0.013), while ERβcx expression was significantly associated with the presence of lymphovascular invasion (p=0.046). There was a significant relationship between ERα expression and low histological grade (p<0.0001). Similarly, ERα+/ERβ+ tumors (p=0.004) and ERα+/ERβcx+ tumors (p=0.008) were significantly associated with low histological grade, too. ERα expression (p=0.009), ERβcx expression (p=0.048) and ERα+/ERβ+ coexpression (p=0.002) increased significantly in progression from normal breast to invasive ductal carcinoma. Expression of ERα correlates with less aggressive phenotypic features, and ERβ expression is positively correlated with ERα expression in breast cancer. ERβcx is associated with aggressive features and can take part in the progression of invasive carcinoma. Increase in ERα+/ERβ+ coexpression, ERα expression and ERβcx expression in breast cancer progression indicates an enhancement in ER expressions or an alteration in expression patterns of different ER variants during mammary carcinogenesis.}, } @article {pmid22333638, year = {2012}, author = {Hata, K and Hirai, I and Tanaka, T and Tanino, H}, title = {[A case of liver metastasis of breast cancer responding to letrozole].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {39}, number = {2}, pages = {257-260}, pmid = {22333638}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Liver Neoplasms/*drug therapy/secondary ; Nitriles/*therapeutic use ; Tomography, X-Ray Computed ; Triazoles/*therapeutic use ; }, abstract = {The patient was a 68-year-old woman who had a right mastectomy performed in another hospital in 1987. Her right breast tumor was histologically diagnosed IDC and ER(-), with an uncertain PgR and HER2. Tamoxifen was administered as adjuvant therapy for five years after surgery. Because she had abdominal pain in January, 2007, she consulted her family doctor. At that doctor's hospital, metastatic tumors of the liver were found, and she was therefore referred to our hospital. A liver biopsy of the tumor was conducted in our hospital, and hormone therapy was also conducted because her cancer status was ER(+), PgR(+), HER2(0), and was not life-threatening. Hormone therapy had a good effect on the tumor. ER, PgR and HER2 expression might make the difference between a primary tumor and a metastatic one, as in this case. Therefore, we should perform biopsies on metastatic tumors to determine the best treatment method. There is a possibility that hormone therapy will become an effective therapeutic procedure for breast cancer patients who are hormone receptor positive, are not in a life threatening situation, and have had a long, disease-free survival. We reported one case in which the aromatase third generation inhibitor letrozole was effective for treating liver metastases of breast cancer.}, } @article {pmid22325669, year = {2014}, author = {Escudero Esteban, R and Gómez Benítez, S and del Estad Cabello, G and Yáñez Fernández, P}, title = {[Granular cell tumour of the breast. A diagnosis to consider].}, journal = {Radiologia}, volume = {56}, number = {1}, pages = {84-88}, doi = {10.1016/j.rx.2011.04.006}, pmid = {22325669}, issn = {1578-178X}, mesh = {Aged ; Breast Neoplasms/*diagnosis ; Female ; Granular Cell Tumor/*diagnosis ; Humans ; Middle Aged ; }, abstract = {The granular cell tumour is a very rare tumour which originates in the Schwann cells, and is generally benign. It is usually located in the head and neck, and its appearance in the breast is uncommon. Although it is rare tumour, granular cell tumours of the breast have a higher prevalence than previously recognised. This tumour usually imitates breast cancer due to its clinical and imaging data, with its diagnosis being by histopathology. The treatment is a wide local excision, and its prognosis is good with a low recurrence rate. We present two cases of granular tumours of the breast in post-menopausal women that simulated a breast carcinoma in the ultrasound and mammography. The first was detected in the breast cancer screening program, and the second during follow up of an invasive ductal carcinoma.}, } @article {pmid22323918, year = {2011}, author = {Bae, SY and Choi, MY and Cho, DH and Lee, JE and Nam, SJ and Yang, JH}, title = {Mucinous carcinoma of the breast in comparison with invasive ductal carcinoma: clinicopathologic characteristics and prognosis.}, journal = {Journal of breast cancer}, volume = {14}, number = {4}, pages = {308-313}, pmid = {22323918}, issn = {2092-9900}, abstract = {PURPOSE: Mucinous carcinoma (MC) of the breast is a rare histologic type of mammary neoplasm. The objective of this study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) of MC.

METHODS: We conducted a retrospective analysis of all MC cases reported to a database between 1994 and 2010. Clinicopathological characteristics and survival of 268 MC cases were reviewed and compared with 2,455 invasive ductal carcinoma-not otherwise specified (IDC-NOS) cases.

RESULTS: The MC cases were of a younger age, involved less lymph nodes, lower stage, more expression of hormonal receptors, and less HER2 overexpression compared to the IDC-NOS cases. The 5-year DFS rate for MC was 95.2% compared to 92.0% for IDC-NOS. The 5-year OS rate for MC was 98.9% compared to 94.9% for IDC-NOS. Multivariate analysis using Cox regression revealed that the mucinous type was a significant prognostic factor for DFS with lower nodal status (N stage) and hormonal therapy. For OS, only N stage was the most significant prognostic factor followed by adjuvant chemotherapy and adjuvant hormonal therapy.

CONCLUSION: MC was shown to be associated with a better DFS than IDC-NOS, but it had a similar OS. Nodal status and adjuvant therapy appear to be more significant predictors of prognosis than histologic subtype.}, } @article {pmid22323917, year = {2011}, author = {Son, BK and Bong, JG and Park, SH and Jeong, YJ}, title = {Ductal carcinoma in situ and sentinel lymph node biopsy.}, journal = {Journal of breast cancer}, volume = {14}, number = {4}, pages = {301-307}, pmid = {22323917}, issn = {2092-9900}, abstract = {PURPOSE: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to evaluate whether sentinel lymph node biopsy (SLNB) is required in patients with an initial diagnosis of ductal carcinoma in situ (DCIS).

METHODS: A retrospective analysis was performed of 78 patients with an initial diagnosis of DCIS between December 2002 and April 2010 and who proceeded to have either SLNB or axillary node dissection performed as part of their primary surgical procedure. The study focused on the rates of axillary node metastasis and the underestimation of invasive carcinoma at an initial diagnosis.

RESULTS: Forty-eight patients underwent SLNB and 18 patients underwent axillary node dissection. Only 1 of 66 patients (1.5%) had a positive sentinel lymph node. After definite surgery, the final diagnosis was changed to invasive ductal carcinoma (IDC) in 12 patients and DCIS with microinvasion in 2 patients; 14 of 78 patients (17.9%) were therefore underestimated at preoperative histological examinations. In 35 patients who were diagnosed DCIS by core needle biopsy (CNB), 13 patients (37.1%) were upstaged into IDC or DCIS with microinvasion in the final diagnosis. The statistically significant factors predictive of invasive breast cancer were a large tumor size and HER2 overexpression.

CONCLUSION: The rates of SLNB positivity in pure DCIS are very low, and there is continuing uncertainty about its clinical importance. However in view of the high rate of underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS, SLNB appears to be appropriate in these patients, especially in the case when DCIS is diagnosed by a core needle biopsy. In patients with an initial diagnosis of DCIS by CNB, SLNB should be considered as part of the primary surgical procedure, when preoperative variables show a tumor larger than 2.35 cm and with HER2 overexpression.}, } @article {pmid22322949, year = {2012}, author = {Lohsiriwat, V and Martella, S and Rietjens, M and Botteri, E and Rotmensz, N and Mastropasqua, MG and Garusi, C and De Lorenzi, F and Manconi, A and Sommario, M and Barbieri, B and Cassilha, M and Minotti, I and Petit, JY}, title = {Paget's disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis.}, journal = {Annals of surgical oncology}, volume = {19}, number = {6}, pages = {1850-1855}, doi = {10.1245/s10434-012-2226-5}, pmid = {22322949}, issn = {1534-4681}, mesh = {Adult ; Breast Neoplasms/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/complications/pathology/surgery ; Carcinoma, Lobular/complications/pathology/surgery ; Female ; Humans ; Incidence ; Italy/epidemiology ; Mastectomy/*adverse effects ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/*diagnosis/surgery ; Neoplasm Staging ; Nipples/*pathology/surgery ; Paget's Disease, Mammary/epidemiology/*etiology ; *Postoperative Complications ; Prognosis ; Risk Assessment ; Risk Factors ; }, abstract = {BACKGROUND: Paget's disease is a rare clinical and histological type of local recurrence (LR) after breast cancer treatment both in case of conservative surgery or nipple-sparing mastectomy (NSM) with or without intraoperative radiation.

METHODS: We performed an analysis of 861 NSM with electron beam intraoperative radiotherapy (ELIOT) patients treated at the European Institute of Oncology from 2002 to 2008, focused on Paget's disease local recurrence.

RESULTS: In 861 patients (713 invasive carcinoma and 148 intraepithelial neoplasia), there were 36 local recurrences (4.18%), and among these were 7 Paget's disease local recurrences (0.8%). Median follow-up was 50 months. Four cases presented with nipple areola complex (NAC) erosions, two crusted lesions, and one ulcerated NAC. The average latency period from the NSM to Paget's disease local recurrence is 32 months (range, 12-49). Complete NAC removal was performed in all seven recurrences. The average follow-up after NAC removal was 47.4 months (range, 20-78). We found neither locoregional relapse nor metastatic event in this group. All patients were alive without disease.

CONCLUSIONS: Paget's disease local recurrence can be found in a significant proportion after NSM. Any suspicious lesion on NAC requires prompt pathological confirmation. Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormonal receptor, high pathological grade, overexpression of HER2/neu, and "HER2 positive (nonluminal)" subtype tend to be significantly associated with more Paget's disease local recurrence and should be followed carefully.}, } @article {pmid22321555, year = {2011}, author = {Liang, L and Fu, J and Liu, YL and Xing, W and Leng, H and Zhang, HW}, title = {[Invasive ductal carcinoma and chronic lymphocytic leukemia: a unique case of collision tumor in breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {40}, number = {10}, pages = {706-707}, pmid = {22321555}, issn = {0529-5807}, mesh = {Antibiotics, Antineoplastic/therapeutic use ; Antineoplastic Agents, Alkylating/therapeutic use ; Antineoplastic Agents, Phytogenic/therapeutic use ; Breast Neoplasms/drug therapy/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology/surgery ; Cyclophosphamide/therapeutic use ; Epirubicin/therapeutic use ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/metabolism/*pathology/surgery ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Multiple Primary/drug therapy/metabolism/*pathology/surgery ; Paclitaxel/therapeutic use ; }, } @article {pmid22316048, year = {2012}, author = {Serrero, G and Hawkins, DM and Yue, B and Ioffe, O and Bejarano, P and Phillips, JT and Head, JF and Elliott, RL and Tkaczuk, KR and Godwin, AK and Weaver, J and Kim, WE}, title = {Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {14}, number = {1}, pages = {R26}, pmid = {22316048}, issn = {1465-542X}, support = {1R43CA124179/CA/NCI NIH HHS/United States ; 2R44CA124179/CA/NCI NIH HHS/United States ; U01CA113916/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; *Neoplasm Recurrence, Local ; Prognosis ; Progranulins ; Receptors, Estrogen/*metabolism ; Retrospective Studies ; }, abstract = {INTRODUCTION: GP88 (progranulin) has been implicated in tumorigenesis and resistance to anti-estrogen therapies for estrogen receptor positive (ER+) breast cancer. Previous pathological studies showed that GP88 is expressed in invasive ductal carcinoma (IDC), but not in normal mammary epithelial tissue, benign lesions or lobular carcinoma. Based on these results, the present study examines GP88 prognostic significance in association with recurrence and death risks for ER+ IDC patients.

METHODS: Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis of paraffin-embedded breast tumor tissue sections from ER+ IDC patients (lymph node positive and negative, stage 1 to 3) in correlation with patients' survival outcomes. The training study established a GP88 cut-off value associated with decreased disease-free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut-off value and compared GP88 prognostic information with other prognostic factors, particularly tumor size, grade, disease stage and lymph node status in multivariate analysis.

RESULTS: GP88 expression is associated with a statistically significant increase in recurrence risk for ER+ IDC patients. The training study established that GP88 3+ score was associated with decreased DFS (P = 0.0004) and OS (P = 0.0036). The independent validation study verified that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88 < 3+. GP88 remained an independent risk predictor after considering age, ethnicity, nodal status, tumor size, tumor grade, disease stage, progesterone receptor expression and treatments.

CONCLUSIONS: The survival factor GP88 is a novel prognostic biomarker, predictive of recurrence risk and increased mortality for non-metastatic ER+ IDC patients. Of importance, our data show that GP88 continues to be a prognostic factor even after five years. These results also provide evidence that GP88 provides prognostic information independent of tumor and clinical characteristics and would support prospective study to examine whether GP88 expression could help stratify patients with ER+ tumors for adjuvant therapy.}, } @article {pmid22315424, year = {2012}, author = {Volinia, S and Galasso, M and Sana, ME and Wise, TF and Palatini, J and Huebner, K and Croce, CM}, title = {Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {8}, pages = {3024-3029}, pmid = {22315424}, issn = {1091-6490}, support = {U01 CA152758/CA/NCI NIH HHS/United States ; U01 CA154200/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Kaplan-Meier Estimate ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; }, abstract = {The transition from ductal carcinoma in situ to invasive ductal carcinoma is a key event in breast cancer progression that is still not well understood. To discover the microRNAs regulating this critical transition, we used 80 biopsies from invasive ductal carcinoma, 8 from ductal carcinoma in situ, and 6 from normal breast. We selected them from a recently published deep-sequencing dataset [Farazi TA, et al. (2011) Cancer Res 71:4443-4453]. The microRNA profile established for the normal breast to ductal carcinoma in situ transition was largely maintained in the in situ to invasive ductal carcinoma transition. Nevertheless, a nine-microRNA signature was identified that differentiated invasive from in situ carcinoma. Specifically, let-7d, miR-210, and -221 were down-regulated in the in situ and up-regulated in the invasive transition, thus featuring an expression reversal along the cancer progression path. Additionally, we identified microRNAs for overall survival and time to metastasis. Five noncoding genes were associated with both prognostic signatures--miR-210, -21, -106b*, -197, and let-7i, with miR-210 the only one also involved in the invasive transition. To pinpoint critical cellular functions affected in the invasive transition, we identified the protein coding genes with inversely related profiles to miR-210: BRCA1, FANCD, FANCF, PARP1, E-cadherin, and Rb1 were all activated in the in situ and down-regulated in the invasive carcinoma. Additionally, we detected differential splicing isoforms with special features, including a truncated EGFR lacking the kinase domain and overexpressed only in ductal carcinoma in situ.}, } @article {pmid22315090, year = {2013}, author = {Alvarez, C and Tapia, T and Cornejo, V and Fernandez, W and Muñoz, A and Camus, M and Alvarez, M and Devoto, L and Carvallo, P}, title = {Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer.}, journal = {Molecular carcinogenesis}, volume = {52}, number = {6}, pages = {475-487}, doi = {10.1002/mc.21881}, pmid = {22315090}, issn = {1098-2744}, mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Base Sequence ; Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; DNA/genetics/isolation & purification ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics ; Nerve Tissue Proteins/*genetics ; Promoter Regions, Genetic ; Repressor Proteins/*genetics ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes.}, } @article {pmid22314475, year = {2012}, author = {Saleh, FM and Ansari, NP}, title = {Invasive ductal carcinoma in a young male breast.}, journal = {Mymensingh medical journal : MMJ}, volume = {21}, number = {1}, pages = {162-164}, pmid = {22314475}, issn = {1022-4742}, mesh = {Adult ; Breast Neoplasms, Male/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Humans ; Male ; Mastectomy ; }, abstract = {Carcinoma arising in the male breast is a rare occurrence. The risk of male breast cancer increases with age, and the median age of diagnosis for men is 10 years later than that for females (67 to 71 years). Because of the absence of lobules in the normal male breast, lobular carcinoma cases are seen infrequently. All of the microscopic types identified in the female breast have been encountered in male but the most frequent is invasive ductal carcinoma and less frequent is invasive lobular carcinoma. We present the case of a 20 years old man presenting with a left breast lump. After left mastectomy with level 2 axillary clearance, histopathological examination revealed infiltrating ductal carcinoma. Our case represents ductal carcinoma in a proven genotypic young male patient showing no exogenous or endogenous estrogens exposure.}, } @article {pmid22311972, year = {2012}, author = {Yeang, HXA and Hamdam, JM and Al-Huseini, LMA and Sethu, S and Djouhri, L and Walsh, J and Kitteringham, N and Park, BK and Goldring, CE and Sathish, JG}, title = {Loss of transcription factor nuclear factor-erythroid 2 (NF-E2) p45-related factor-2 (Nrf2) leads to dysregulation of immune functions, redox homeostasis, and intracellular signaling in dendritic cells.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {13}, pages = {10556-10564}, pmid = {22311972}, issn = {1083-351X}, support = {G0700420/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; G0700654/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/metabolism ; Dendritic Cells/cytology/*metabolism ; Glutathione/genetics/metabolism ; Histone Deacetylases/genetics/metabolism ; Homeostasis/*physiology ; MAP Kinase Signaling System/*physiology ; Mice ; Mice, Knockout ; NF-E2-Related Factor 2/genetics/*metabolism ; NF-kappa B/genetics/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/*metabolism ; p38 Mitogen-Activated Protein Kinases/genetics/metabolism ; }, abstract = {Dendritic cells (DCs) are critical mediators of immunity and immune tolerance by orchestrating multiple aspects of T cell activation and function. Immature DCs (iDCs) expressing low levels of co-stimulatory receptors are highly efficient at antigen capture but are poor activators of T cells. Maturation of DCs is associated with increased expression of co-stimulatory molecules. Co-stimulatory receptor gene expression is regulated by intracellular redox, NF-κB, and MAPK pathways and by histone deacetylase (HDAC) activity. The transcription factor, Nrf2, is important for maintaining intracellular glutathione (GSH) levels and redox homeostasis and has been implicated in modulating DC co-stimulatory receptor expression. It is unclear whether Nrf2 mediates this effect by GSH-dependent mechanisms and whether it influences DC signaling pathways. Using bone marrow-derived iDCs from Nrf2(+/+) and Nrf2(-/-) mice, we demonstrate that Nrf2(-/-) iDCs have lower basal GSH levels, enhanced co-stimulatory receptor expression, impaired phagocytic functions, and increased antigen-specific CD8 T cell stimulation capacity. Interestingly, lowering GSH levels in Nrf2(+/+) iDCs did not recapitulate the Nrf2(-/-) iDC phenotype. Loss of Nrf2 resulted in elevated basal levels of reactive oxygen species but did not affect basal NF-κB activity or p38 MAPK phosphorylation. Using pharmacological inhibitors, we demonstrate that enhanced co-stimulatory receptor phenotype of Nrf2(-/-) iDC does not require ERK activity but is dependent on HDAC activity, indicating a potential interaction between Nrf2 function and HDAC. These results suggest that Nrf2 activity is required to counter rises in intracellular reactive oxygen species and to regulate pathways that control DC co-stimulatory receptor expression.}, } @article {pmid22311582, year = {2013}, author = {Sakamoto, N and Tozaki, M and Hoshi, K and Fukuma, E}, title = {Is MRI useful for the prediction of nipple involvement?.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {20}, number = {4}, pages = {316-322}, doi = {10.1007/s12282-012-0338-1}, pmid = {22311582}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis ; Carcinoma, Lobular/*diagnosis ; Female ; Humans ; Magnetic Resonance Imaging/*statistics & numerical data ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Nipples/*pathology ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: The purpose of this retrospective study was to examine the usefulness of MRI for predicting nipple involvement.

METHODS: A retrospective review was performed of 81 breasts in 78 breast cancer patients who had undergone nipple or nipple-areolar complex resections during surgery. The enhancement patterns of the nipple on MRI were compared to the contralateral side and were categorized as no enhancement, bilateral enhancement, and unilateral enhancement. The physical examination results, MRI findings, and pathological findings were assessed.

RESULTS: Nipple involvement was observed in 17 of 81 nipples (21%), of which one exhibited infiltration of invasive ductal carcinoma, 12 exhibited ductal carcinoma in situ, and four exhibited Paget's disease. The nipples with no enhancement or with bilateral enhancement on MRI showed a lower rate of nipple involvement than the nipples with unilateral enhancement (0/48 vs. 17/33, p < 0.001). Among the unilaterally enhanced nipples, those with continuous enhancement from the index lesion showed a higher rate of nipple involvement than those without continuous enhancement (16/26 vs. 1/7, p = 0.03). When the enhancement characteristics of the unilaterally enhanced nipples were categorized, the findings with relatively high positive predictive values for nipple involvement were diffuse enhancement (100%, 2/2), unilateral skin enhancement (100%, 2/2), rim enhancement (86%, 6/7), and periductal enhancement (80%, 4/5).

CONCLUSIONS: MRI was useful for predicting nipple involvement. Unilateral enhancement of the nipple with continuous enhancement from the index lesion may suggest the possibility of nipple involvement.}, } @article {pmid22311262, year = {2012}, author = {Wang, S and Li, W and Liu, N and Zhang, T and Liu, H and Liu, J and Liu, F and Zhang, W and Gebreamlak, EP and Niu, Y}, title = {Clinicopathologic characteristics and prognosis for molecular subtypes in low-grade breast carcinoma: comparison with grade one invasive ductal carcinoma-not otherwise specified.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {4}, pages = {2556-2564}, pmid = {22311262}, issn = {1559-131X}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {The aim of this study was to investigate the clinicopathologic characteristics and prognosis value for molecular subtypes of low-grade breast carcinoma (LGBC) compared with grade one invasive ductal carcinoma-not otherwise specified (G1-IDC-NOS). A retrospective review of 688 LGBC and 1 037 G1-IDC-NOS patients was classified into four different molecular subtypes based on the IHC-based definitions for ER, PR, and c-erbB-2. In LGBC, lymph node metastasis, the percentage of III/IV TNM stages, the expression of Ki-67 and p53 in luminal A subtype were lower than in other subtypes (P<0.01). In addition, the variations of Ki-67 and p53 expression were observed in different subtypes of G1-IDC-NOS (P<0.01). Compared with G1-IDC-NOS, LGBC has higher proportion in the ER positive, PR positive, HER-2 negative, luminal A subtype, Ki-67 negative, and lymph nodes negative group (P<0.01). Furthermore, the overall survival of luminal A and luminal B is higher than triple-negative and HER-2/neu subtype both in LGBC and G1-IDC-NOS in 262 LGBC and 330 G1-IDC-NOS patients with proper follow-up. The classification of molecular subtype together with clinicopathologic factors can significantly improve the traditional prognosticators in predicting outcome for LGBC and G1-IDC-NOS. And it may contribute to guide the treatment for LGBC and G1-IDC-NOS in the future.}, } @article {pmid22309790, year = {2012}, author = {Shaikh, AY and LaCombe, MA and Du, H and Raghavan, VT and Nanda, RK and Bloomer, WD}, title = {Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up.}, journal = {Radiation oncology (London, England)}, volume = {7}, number = {}, pages = {17}, pmid = {22309790}, issn = {1748-717X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*radiotherapy/surgery ; Carcinoma, Lobular/pathology/*radiotherapy/surgery ; Dose Fractionation, Radiation ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Grading ; Prognosis ; *Radiotherapy, Intensity-Modulated ; Retrospective Studies ; }, abstract = {BACKGROUND: There are limited data on accelerated partial breast irradiation (APBI) using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC) are suitable for APBI.

METHODS: The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC), ILC, or Tis (DCIS) treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF) was pathologically confirmed as a local failure (LF) or an elsewhere failure (EF).

RESULTS: Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9%) including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent.

CONCLUSIONS: External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not differentiate a subset of patients with a higher rate of IBF. APBI may be an appropriate treatment for women with DCIS and ILC.}, } @article {pmid22308937, year = {2011}, author = {Castello Botia, I and Wanden-Berghe, C}, title = {[New classification of causes of mortality of nutritional origin by means of the Delphi method].}, journal = {Archivos latinoamericanos de nutricion}, volume = {61}, number = {2}, pages = {120-126}, pmid = {22308937}, issn = {0004-0622}, mesh = {*Cause of Death ; *Consensus ; *Delphi Technique ; Humans ; *International Classification of Diseases ; Nutrition Disorders/*classification/*mortality ; Nutritional Status ; }, abstract = {The causes of mortality of nutritional origin (MNO) are not classified in the consecutive reviews of the international disease classification (IDC) and there is no agreement for their most proper classification. The objective of this study is to elaborate, using the last ICD as a guide, a list of causes of mortality of nutritional origin which will be used as a reference in future studies. A two round Delphi method was organized with an expert's consenssus in clinical nutrition. The experts were asked to classify a list of causes of MNO in 4 groups; 1) group A: congenital errors related to nutrition, 2) group B: Causes associated with other pathologies, 3) group 3: Excess and defect nutrition disorders, and 4) excluded. In total, 86 causes of MNO were taken under the consensus of experts, and 79 (91.9%) came to an agreement. 14 (17.7%) causes were classified in group A, 5 (6.3%) causes in group B, 37 (46.8%) causes in group C and 23 (29.1%) were excluded. This is a first approach to the classification of mortality causes of nutritional origin, probably due to the ambiguity and disparity of opinions between experts with respect to these causes. This new classification will be very useful due to the fact that it will enable homogenization of the studies and that way we will have comparable studies, using it as a clarifier annex for the ICD of the moment.}, } @article {pmid22306821, year = {2012}, author = {Doron, G and Sar-El, D and Mikulincer, M}, title = {Threats to moral self-perceptions trigger obsessive compulsive contamination-related behavioral tendencies.}, journal = {Journal of behavior therapy and experimental psychiatry}, volume = {43}, number = {3}, pages = {884-890}, doi = {10.1016/j.jbtep.2012.01.002}, pmid = {22306821}, issn = {1873-7943}, mesh = {Adolescent ; Adult ; Affect ; Anxiety/psychology ; Depression/psychology ; Female ; Humans ; Male ; Middle Aged ; *Morals ; Obsessive-Compulsive Disorder/*psychology ; Phobic Disorders/*psychology ; Repetition Priming ; *Self Concept ; Stress, Psychological/psychology ; }, abstract = {BACKGROUND AND OBJECTIVES: Obsessive compulsive (OC) phenomena such as contamination fears may lead to significant impairment in daily functioning. In this research, we examined whether threat to moral self-perceptions can trigger contamination-related behavioral tendencies.

METHOD: Three experiments examined the influence of subtle priming of morality-related information on contamination-related behavioral tendencies.

RESULTS: Subtle suggestions of incompetence in the morality self-domain led to heightened OC-related behavioral tendencies. These effects were specific to self-relevant (versus other-relevant), negative (versus positive) information about the morality domain (versus a morality-irrelevant domain). Findings were not related to pre-existing variations in self-esteem, stress, anxiety, or depression, and were not explained by mood fluctuations.

LIMITATIONS: Our studies were conducted with non-clinical samples.

CONCLUSIONS: Self-sensitivities in the moral domain may be causally linked with contamination-related concerns. Treatments addressing such sensitivities may prove useful when treating obsessive compulsive phenomena.}, } @article {pmid22292636, year = {2011}, author = {Wang, ZH and Gong, JL and Yu, M and Yang, H and Lai, JH and Ma, MX and Wu, H and Li, L and Tan, DY}, title = {Up-regulation of human arrest-defective 1 protein is correlated with metastatic phenotype and poor prognosis in breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {8}, pages = {1973-1977}, pmid = {22292636}, issn = {2476-762X}, mesh = {Acetyltransferases/biosynthesis/*genetics/metabolism ; Adult ; Breast Cyst/genetics/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/*pathology/secondary ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Female ; Fibroadenoma/genetics/metabolism/pathology ; Humans ; Hyperplasia/genetics/metabolism/pathology ; Immunohistochemistry ; Inflammation/genetics/metabolism/pathology ; Lymphatic Metastasis ; Middle Aged ; N-Terminal Acetyltransferase A ; N-Terminal Acetyltransferase E ; Phenotype ; Postoperative Period ; Prognosis ; Up-Regulation ; }, abstract = {BACKGROUND: Human arrest defective 1 protein (ARD1), as a N-terminal acetyltransferase, has been reported to play a crucial role in tumorigenesis, but the results are somewhat controversial. To explore the clinical and pathological significance of ARD1 in breast tumorigenesis, we analyzed ARD1 status in multiple types of breast disease.

METHODS: The expression of ARD1 protein was assessed by immunohistochemistry in 356 cases including 82 invasive ductal carcinomas (IDC), 159 fibroadenomas, 66 hyperplasia of mammary glands, 19 inflammatory breast disease, 30 breast cysts, and in 29 postoperative treatment patients. We assessed the relationship of ARD1 protein with clinical and pathological characteristics using χ2 test.

RESULTS: ARD1 protein was observed at 61.0% (50/82), 54.7% (87/159), 37.9% (25/66), 36.8% (7/19) in IDC, fibroadenoma, hyperplasia, and inflammation, respectively, and less than 30.0% for breast cyst. Thus, high ARD1 expression correlated with breast cancer (relative risk = 1.32, P < 0.005). Moreover, the level of ARD1 protein in carcinoma patients was distinctly related to lymph node metastasis and ER status, with 94.0% (47/50) as copmpared to 6.0% (3/50) in metastatic and non-metastatic (P < 0.001), and 84.0% (42/50) and 16.0% (8/50) for ER + and ER - (P < 0.01), respectively. In addition, the level of ARD1 appeared to have potential for evaluation of prognosis in breast cancer patients after postoperative therapy.

CONCLUSIONS: These results suggest that ARD1 expression may be as a potential target for exploring the mechanism of breast cancer metastasic to lymph nodes and hormone-responsive regulation.}, } @article {pmid22287988, year = {2011}, author = {Muttarak, M and Siriya, B and Kongmebhol, P and Chaiwun, B and Sukhamwang, N}, title = {Paget's disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients.}, journal = {Biomedical imaging and intervention journal}, volume = {7}, number = {2}, pages = {e16}, pmid = {22287988}, issn = {1823-5530}, abstract = {OBJECTIVES: To determine the clinical, imaging and pathological findings of Paget's disease of the breast.

MATERIALS AND METHODS: Approval by Institutional Review Board was granted and informed consent was waived. Retrospective review of the pathological diagnosis of 2,361 women with breast carcinoma between January 2004 and April 2010 revealed 27 patients with Paget's disease of the breast. The clinical, mammographic and ultrasonographic images were retrospectively reviewed.

RESULTS: The prevalence of Paget's disease of the breast was 1.14% of all breast carcinoma at this institution. Of the 27 patients with Paget's disease, only 16 had imaging studies and this group constituted the basis of this study. All 16 patients were women, with ages ranging from 36-68 years (mean age 50.31 years). Eleven patients presented with clinical findings suggestive of Paget's disease of the breast. Seven of these 11 patients also had associated palpable mass(es). Four patients presented with a palpable mass alone and one presented with bloody nipple discharge alone. Mammography was performed in all 16 patients and ultrasonography (US) in 15 patients. Of the 16 mammographic studies, two were negative. Of the 15 US studies, three were negative. Of these three negative US studies, two also had negative mammography and one had pleomorphic microcalcifications on mammogram. US was helpful in detecting multifocality in two patients. Mammography was 100% positive in patients who presented with palpable breast mass(es) and bloody nipple discharge, but 50% positive in patients who had clinically suggestive Paget's disease alone. Almost all patients (15/16) had underlying breast malignancies. Seven patients had multifocality or multicentricity. Modified radical mastectomy was performed in 13 patients, simple mastectomy in two, and wide local excision in one patient. Pathological findings were ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 10), metaplastic carcinoma (n = 1), invasive lobular carcinoma (ILC) (n = 1), and only Paget's disease of the nipple without underlying breast carcinoma (n = 1).

CONCLUSION: Patients with Paget's disease of the breast have a high incidence of an underlying breast carcinoma. Most of the patients in this study presented late and were more likely to have positive mammograms. Mammography should be performed to identify the underlying breast carcinoma. Those who have only nipple areolar changes and no palpable mass have less positive mammography and less invasive carcinoma.}, } @article {pmid22285093, year = {2012}, author = {Matsumoto, K and Tanaka, H and Tatsumi, K and Miyoshi, T and Hiraishi, M and Kaneko, A and Tsuji, T and Ryo, K and Fukuda, Y and Yoshida, A and Kawai, H and Hirata, K}, title = {Left ventricular dyssynchrony using three-dimensional speckle-tracking imaging as a determinant of torsional mechanics in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {109}, number = {8}, pages = {1197-1205}, doi = {10.1016/j.amjcard.2011.11.059}, pmid = {22285093}, issn = {1879-1913}, mesh = {Aged ; Cardiac Resynchronization Therapy ; Cardiomyopathy, Dilated/*diagnostic imaging/physiopathology/therapy ; Case-Control Studies ; Echocardiography, Doppler/methods ; Echocardiography, Three-Dimensional/methods ; Female ; Heart Ventricles/*diagnostic imaging/physiopathology ; Humans ; Male ; Reproducibility of Results ; Stroke Volume/physiology ; Torsion Abnormality/*diagnostic imaging ; Ventricular Dysfunction, Left/*diagnostic imaging/physiopathology/therapy ; }, abstract = {The aim of this study was to use 3-dimensional (3D) speckle-tracking echocardiography to test the hypothesis that left ventricular (LV) dyssynchrony may negatively affect LV torsional mechanics in patients with idiopathic dilated cardiomyopathy (IDC) and that LV torsion may improve after cardiac resynchronization therapy. This study included 65 subjects; 20 with IDC with ejection fractions ≤35% and wide QRS complexes (≥120 ms), 20 with IDC with ejection fractions ≤35% and narrow QRS complexes (<120 ms), and 25 controls. LV dyssynchrony index was determined as the SD of time to peak 3D speckle-tracking radial strain and regional heterogeneity of LV rotation (rotational dispersion index) as the SD of 3D speckle-tracking time to peak rotation. All rotational indexes were significantly impaired in patients with IDC, while LV torsion in patients with IDC with wide QRS complexes was significantly smaller than that in patients with IDC with narrow QRS complexes and controls. Conversely, LV dyssynchrony index (127.3 ± 24.0 ms [p <0.01 vs controls and vs patients with narrow QRS complexes] vs 88.8 ± 22.5 ms [p <0.01 versus controls] vs 30.9 ± 10.0 ms) and rotational dispersion index (115.1 ± 27.5 ms [p <0.01 vs controls and vs patients with narrow QRS complexes] vs 96.0 ± 23.4 ms [p <0.01 versus controls] vs 45.0 ± 13.7 ms) were significantly higher in patients with IDC with wide QRS complexes. Multivariate analysis showed that the LV ejection fraction (β = 0.688, p <0.001) and rotational dispersion index (β = -0.249, p <0.01) were independent determinants of LV torsion. Moreover, LV torsion in patients with IDC with wide QRS complexes improved after cardiac resynchronization therapy (p <0.05), along with reductions in LV dyssynchrony and rotational dispersion indexes. In conclusion, these findings obtained with a novel 3D speckle-tracking system feature a novel aspect of LV torsional mechanics and demonstrate its association with LV dyssynchrony.}, } @article {pmid22277312, year = {2012}, author = {Nagao, T and Kinoshita, T and Hojo, T and Tsuda, H and Tamura, K and Fujiwara, Y}, title = {The differences in the histological types of breast cancer and the response to neoadjuvant chemotherapy: the relationship between the outcome and the clinicopathological characteristics.}, journal = {Breast (Edinburgh, Scotland)}, volume = {21}, number = {3}, pages = {289-295}, doi = {10.1016/j.breast.2011.12.011}, pmid = {22277312}, issn = {1532-3080}, mesh = {Breast Neoplasms/*classification/epidemiology/pathology/*therapy ; Carcinoma/*classification/epidemiology/pathology/*therapy ; Chemotherapy, Adjuvant ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Japan ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; *Women's Health ; }, abstract = {UNLABELLED: Although effective regimens have been established for invasive ductal carcinoma-not otherwise specified (IDC), the efficacy and prognosis of other minor types of breast cancer are unknown because of their rareness. The clinicopathological features and prognosis of other minor types concerning the response to neoadjuvant chemotherapy (NAC) were evaluated in this study. A total of 562 patients were classified according to the Japanese and the World Health Organization (WHO) classifications, and the number of IDC and other special types (SP) was 500 and 62. The SP patients had a significantly poorer clinicopathological response to NAC and less breast-conservative therapy than those with IDC. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma also responded poorly, and patients with metaplastic carcinomas and invasive lobular carcinoma had a significantly poorer prognosis. Despite the poor response to chemotherapy, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis. The response to NAC and the prognosis vary for each histological type. For some types, the prognosis was not related to the clinicopathological response to NAC.

BACKGROUND: In the treatment of breast cancer, neoadjuvant chemotherapy (NAC) has become the standard treatment modality for downstaging purposes. Although effective regimens have been established for the treatment of invasive ductal carcinoma-not otherwise specified (IDC), the data about the efficacy and prognosis for patients with other minor types of breast cancer are insufficient because of the rareness of these tumors. Defining the relationship between each histological type and the clinicopathological response to NAC is essential to optimizing individualized treatment.

METHODS: We retrospectively evaluated the clinicopathological features and classification of the histological types based on the Japanese and the World Health Organization (WHO) classifications before and after NAC in 562 patients with primary breast cancer who underwent curative treatment after NAC between 1998 and 2008. The prognosis was estimated for each histological type.

RESULTS: Of the 562 patients, the number of cases of IDC and other special types (SP) was 500 and 62. In the SP group, the clinicopathological response to NAC was significantly poorer, and the patients underwent breast-conservative therapy less frequently than did the IDC patients. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma responded poorly to NAC. The disease-free survival and overall survival were significantly worse for patients with metaplastic carcinomas (p<0.001 and p<0.001) and with invasive lobular carcinoma (p=0.03 and p<0.001) than other cancers. Despite their poor response to treatment, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis.

CONCLUSIONS: The response to standardized NAC and prognosis varies for each histological type. For some types, the prognosis was not associated with the clinicopathological response to NAC. Innovative regimens should therefore be investigated for each histological type to achieve the best response.}, } @article {pmid22276203, year = {2012}, author = {Bastea, LI and Döppler, H and Balogun, B and Storz, P}, title = {Protein kinase D1 maintains the epithelial phenotype by inducing a DNA-bound, inactive SNAI1 transcriptional repressor complex.}, journal = {PloS one}, volume = {7}, number = {1}, pages = {e30459}, pmid = {22276203}, issn = {1932-6203}, support = {CA116201-03DR4/CA/NCI NIH HHS/United States ; R01 CA140182/CA/NCI NIH HHS/United States ; GM086438/GM/NIGMS NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; CA140182/CA/NCI NIH HHS/United States ; R01 GM086435/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cadherins/metabolism ; Cell Line ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DNA/*metabolism ; Dogs ; Epithelial Cells/*metabolism ; Female ; Humans ; Immunoblotting ; Immunoprecipitation ; In Vitro Techniques ; LIM Domain Proteins/metabolism ; Mammary Glands, Animal/cytology ; Mice ; Microscopy, Fluorescence ; Phosphorylation ; Protein Kinase C/*metabolism ; Snail Family Transcription Factors ; Tissue Array Analysis ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Protein kinase D1 is downregulated in its expression in invasive ductal carcinoma of the breast and in invasive breast cancer cells, but its functions in normal breast epithelial cells is largely unknown. The epithelial phenotype is maintained by cell-cell junctions formed by E-cadherin. In cancer cells loss of E-cadherin expression contributes to an invasive phenotype. This can be mediated by SNAI1, a transcriptional repressor for E-cadherin that contributes to epithelial-to-mesenchymal transition (EMT).

Here we show that PKD1 in normal murine mammary gland (NMuMG) epithelial cells is constitutively-active in its basal state and prevents a transition to a mesenchymal phenotype. Investigation of the involved mechanism suggested that PKD1 regulates the expression of E-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor SNAI1. PKD1-mediated phosphorylation of SNAI1 occurs in the nucleus and generates a nuclear, inactive DNA/SNAI1 complex that shows decreased interaction with its co-repressor Ajuba. Analysis of human tissue samples with a newly-generated phosphospecific antibody for PKD1-phosphorylated SNAI1 showed that regulation of SNAI1 through PKD1 occurs in vivo in normal breast ductal tissue and is decreased or lost in invasive ductal carcinoma.

CONCLUSIONS/SIGNIFICANCE: Our data describe a mechanism of how PKD1 maintains the breast epithelial phenotype. Moreover, they suggest, that the analysis of breast tissue for PKD-mediated phosphorylation of SNAI1 using our novel phosphoS11-SNAI1-specific antibody may allow predicting the invasive potential of breast cancer cells.}, } @article {pmid22271313, year = {2012}, author = {Raviraj, V and Zhang, H and Chien, HY and Cole, L and Thompson, EW and Soon, L}, title = {Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas.}, journal = {Clinical & experimental metastasis}, volume = {29}, number = {3}, pages = {273-292}, pmid = {22271313}, issn = {1573-7276}, mesh = {Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Cell Movement ; Collagen Type II/analysis ; Cyclin-Dependent Kinase Inhibitor p27/physiology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry ; Keratin-19/analysis ; Neoplasm Invasiveness ; Tumor Microenvironment ; Vimentin/analysis ; rho-Associated Kinases/physiology ; }, abstract = {Mortality in breast cancer is linked to metastasis and recurrence yet there is no acceptable biological model for cancer relapse. We hypothesise that there might exist primary tumour cells capable of escaping surgery by migration and resisting radiotherapy and chemotherapy to cause cancer recurrence. We investigated this possibility in invasive ductal carcinoma (IDC) tissue and observed the presence of solitary primary tumour cells (SPCs) in the dense collagen stroma that encapsulates intratumoural cells (ICs). In IDC tissue sections, collagen was detected with either Masson's Trichrome or by second harmonics imaging. Cytokeratin-19 (CK-19) and vimentin (VIM) antibodies were, respectively, used to identify epithelial-derived tumour cells and to indicate epithelial to mesenchymal transition (EMT). Confocal/multiphoton microscopy showed that ICs from acini were mainly CK-19(+ve) and were encapsulated by dense stromal collagen. Within the stroma, SPCs were detected by their staining for both CK-19 and VIM (confirming EMT). ICs and SPCs were subsequently isolated by laser capture microdissection followed by multiplex tandem-PCR studies. SPCs were found to be enriched for pro-migratory and anti-proliferative genes relative to ICs. In vitro experiments using collagen matrices at 20 mg/cm(3), similar in density to tumour matrices, demonstrated that SPC-like cells were highly migratory but dormant, phenotypes that recapitulated the genotypes of SPCs in clinical tissue. These data suggest that SPCs located at the breast cancer perimeter are invasive and dormant such that they may exceed surgical margins and resist local and adjuvant therapies. This study has important connotations for a role of SPCs in local recurrence.}, } @article {pmid22270930, year = {2012}, author = {Zhao, X and Mirza, S and Alshareeda, A and Zhang, Y and Gurumurthy, CB and Bele, A and Kim, JH and Mohibi, S and Goswami, M and Lele, SM and West, W and Qiu, F and Ellis, IO and Rakha, EA and Green, AR and Band, H and Band, V}, title = {Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {134}, number = {1}, pages = {171-180}, pmid = {22270930}, issn = {1573-7217}, support = {R01 CA087986/CA/NCI NIH HHS/United States ; CA105489/CA/NCI NIH HHS/United States ; U01 CA151806/CA/NCI NIH HHS/United States ; CA116552/CA/NCI NIH HHS/United States ; R01 CA116552/CA/NCI NIH HHS/United States ; CA99163/CA/NCI NIH HHS/United States ; R01 CA099163/CA/NCI NIH HHS/United States ; CA144027/CA/NCI NIH HHS/United States ; 5U01CA151806-02/CA/NCI NIH HHS/United States ; CA87986/CA/NCI NIH HHS/United States ; R01 CA096844/CA/NCI NIH HHS/United States ; CA96844/CA/NCI NIH HHS/United States ; R01 CA144027/CA/NCI NIH HHS/United States ; R01 CA105489/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Antibody Specificity ; Biomarkers, Tumor/genetics/*metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/pathology ; Carrier Proteins/genetics/immunology/*metabolism ; Cohort Studies ; Disease-Free Survival ; Female ; Gene Expression ; Humans ; Hyperplasia/metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.}, } @article {pmid22268614, year = {2012}, author = {Voss, A and Goernig, M and Schroeder, R and Truebner, S and Schirdewan, A and Figulla, HR}, title = {Blood pressure variability as sign of autonomic imbalance in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {35}, number = {4}, pages = {471-479}, doi = {10.1111/j.1540-8159.2011.03312.x}, pmid = {22268614}, issn = {1540-8159}, mesh = {Arrhythmias, Cardiac/mortality ; Autonomic Nervous System/*physiopathology ; Blood Pressure/*physiology ; Cardiomyopathy, Dilated/*physiopathology ; Death, Sudden, Cardiac/epidemiology ; Electrocardiography/methods ; Female ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Risk ; }, abstract = {BACKGROUND: The problem of identifying idiopathic dilated cardiomyopathy (IDC) patients who are at risk of sudden death is still unsolved. The presence of autonomic imbalance in patients with IDC might predict sudden death and tachyarrhythmic events. The aim of this study was to analyze the suitability of blood pressure variability (BPV) compared to heart rate variability (HRV) for noninvasive risk stratification in IDC patients.

METHODS: Continuous noninvasive blood pressure and high-resolution electrocardiogram were recorded from 91 IDC patients for 30 minutes. During a median follow-up period of 28 months (range: [17-38] months), 14 patients died due to sudden death or necessary resuscitation due to a life-threatening arrhythmia. HRV and BPV analyses were performed in time domain, frequency domain, and nonlinear dynamics. Using the Mann-Whitney U test and Cox regression, we estimated the accuracy of clinical and nonclinical parameters in discriminating high-risk from low-risk patients.

RESULTS: Dynamics of blood pressure regulation was significantly changed in high-risk patients, indicating an increased BPV. BPV indexes from nonlinear symbolic dynamics revealed significant univariate (sensitivity: 85.7%; specificity 77.9%; area under receiver-operator characteristics [ROC] curve: 87.8%) differences. In an optimum multivariate set consisting of two clinical indexes (left ventricular end-diastolic diameter, New York Heart Association) and one nonlinear index (symbolic dynamics), highly significant differences between low- and high-risk IDC groups were estimated (sensitivity of 92.9%, specificity of 86.5%, and area under ROC curve of 95.3%).

CONCLUSION: Diastolic BPV indexes, especially those from symbolic dynamics, appear to be useful for risk stratification of sudden death in patients with IDC.}, } @article {pmid22259834, year = {2011}, author = {Yamazaki, M and Nagata, Y and Monji, S and Shigematsu, Y and Baba, T and Shimokawa, H and Uramoto, H and Yamada, S and Hanagiri, T and Tanaka, F}, title = {Apocrine carcinoma of the breast.}, journal = {Journal of UOEH}, volume = {33}, number = {4}, pages = {293-301}, doi = {10.7888/juoeh.33.293}, pmid = {22259834}, issn = {0387-821X}, mesh = {*Apocrine Glands/pathology ; Axilla/surgery ; Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/pathology/*surgery ; Carcinoma, Ductal, Breast/diagnosis/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Time Factors ; }, abstract = {Apocrine carcinoma is a rare variant of breast carcinoma, and accounts for 0.3 to 1.0% of all breast cancers. A 55-year-old Japanese female patient presented with a right breast tumor, which had been detected by mass-screening, and she was admitted to our hospital. The physical examination revealed an elastic hard lump in the upper lateral quadrant of the right breast. The tumor size was approximately 1.0 cm in diameter, and the border was clear. There were no palpable axillary lymph nodes nor supraclavicular nodes. Fine-needle aspiration cytology revealed invasive ductal carcinoma. The patient underwent a partial resection of the right breast (breast conserving therapy) and a right axillary lymphadenectomy. Macroscopically, the resected specimen revealed a white tumor measuring 1.2 x 1.2 x 1.0 cm. The TNM classification was diagnosed as T1cN0M0 stage I. Histopathologically, the tumor revealed a proliferation of atypical epithelial cells with apocrine differentiation, arranged in a papillotubular or cribriform growth pattern with stromal invasion. The tumor cells showed irregular round-shaped nuclei often containing prominent nucleoli, and had particularly abundant eosinophilic granular cytoplasm. In the immunohistochemical analysis, these carcinoma cells were positive for Gross Cystic Disease Fluid Protein 15 and the androgen receptor, whereas they were negative for the estrogen and progesterone receptors. Immunohistochemical staining for Her2 using the HercepTest was found to be negative (score 0). Thus, the pathological diagnosis was apocrine carcinoma. There were no metastases in the axillary lymph nodes. The patient has had no recurrence in 8 years after surgery.}, } @article {pmid22259257, year = {2012}, author = {Abu-Rahmeh, Z and Nseir, W and Naroditzky, I}, title = {Invasive ductal carcinoma within fibroadenoma and lung metastases.}, journal = {International journal of general medicine}, volume = {5}, number = {}, pages = {19-21}, pmid = {22259257}, issn = {1178-7074}, abstract = {Fibroadenomas are one of the most common benign tumors of the breast. Malignant transformation from fibroadenoma to cancer is rare. We present a case of an invasive ductal carcinoma within an otherwise benign fibroadenoma with lung metastasis in a 69-year-old woman.}, } @article {pmid22252965, year = {2012}, author = {Hernandez, L and Wilkerson, PM and Lambros, MB and Campion-Flora, A and Rodrigues, DN and Gauthier, A and Cabral, C and Pawar, V and Mackay, A and A'Hern, R and Marchiò, C and Palacios, J and Natrajan, R and Weigelt, B and Reis-Filho, JS}, title = {Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection.}, journal = {The Journal of pathology}, volume = {227}, number = {1}, pages = {42-52}, pmid = {22252965}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; CTR-Q3REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; IM-CTR-HER2REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Class I Phosphatidylinositol 3-Kinases ; Clonal Evolution ; Clone Cells ; Comparative Genomic Hybridization ; *DNA Mutational Analysis ; DNA, Neoplasm/analysis ; Disease Progression ; Female ; *Gene Expression Profiling ; *Genetic Heterogeneity ; Genomics/methods ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mutation ; Neoplasms, Multiple Primary ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, and the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCI and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDC were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY (Oncocarta v 1.0 panel). Fluorescence in situ hybridization and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCI and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (ie 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations.}, } @article {pmid22249792, year = {2011}, author = {Lucarelli, AP and Martins, MM and Montor, W and Oliveira, V and Galvão, MA and Piato, S}, title = {Cyclooxygenase-2 and human epidermal growth factor receptor type 2 (HER-2) expression simultaneously in invasive and in situ breast ductal carcinoma.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {129}, number = {6}, pages = {371-379}, doi = {10.1590/s1516-31802011000600002}, pmid = {22249792}, issn = {1806-9460}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; Cyclooxygenase 2/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Necrosis ; Neoplasm Proteins/*metabolism ; Receptor, ErbB-2/*metabolism ; Up-Regulation ; }, abstract = {CONTEXT AND OBJECTIVE: Cyclooxygenase-2 (COX-2) and human epidermal growth factor receptor type 2 (HER-2) are associated with tumorigenesis. Studies have shown that HER-2 can regulate COX-2 expression. The aim of this study was to evaluate the correlation between COX-2 and HER-2 expression in normal breast epithelium and in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast.

DESIGN AND SETTING: Cross-sectional study at the Mastology Unit of the Department of Gynecology and Obstetrics, Santa Casa de Misericórdia de São Paulo Hospital.

METHODS: COX-2 and HER-2 were detected using immunohistochemistry on 100 tissue fragments. HER-2 > +2 was subjected to fluorescence in situ hybridization (FISH).

RESULTS: COX-2 expression was detected in 87%, 85% and 75% of IDC, DCIS and normal epithelium, respectively. HER-2 expression was detected in 34% of IDC and 34% of DCIS. COX-2 in DCIS correlated with HER-2 in IDC (P = 0.049) and DCIS (P = 0.049). COX-2 in normal epithelium correlated with HER-2 in IDC (P = 0.046) and DCIS (P = 0.046). COX-2 in IDC was not associated with HER-2 (P = 0.235). Comparison between COX-2 and HER-2 in DCIS showed that there was a statistically significant difference with regard to nuclear grades II and III and presence of comedonecrosis (P < 0.001). In IDC, there was significant expression with nuclear grades II and III and histological grade II (P < 0.001).

CONCLUSIONS: Our findings provide evidence that HER-2 and COX-2 regulate each other.}, } @article {pmid22246908, year = {2011}, author = {Marczyk, E and Kruczak, A and Ambicka, A and Mularz, K and Harazin-Lechowska, A and Moskal, J and Sokołowski, A and Mituś, J and Ryś, J}, title = {The routine immunohistochemical evaluation in Paget disease of the nipple.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {62}, number = {4}, pages = {229-235}, pmid = {22246908}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/mortality/*pathology ; Cell Count ; Female ; Humans ; Ki-67 Antigen/metabolism ; Menopause ; Middle Aged ; Neoplasms, Multiple Primary ; Paget's Disease, Mammary/metabolism/mortality/*pathology ; Poland/epidemiology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {Paget disease (PD) of the nipple with coexisting intraductal (DCIS) and invasive carcinoma of the breast comprises 0.6-1.8% of all malignant epithelial neoplasms of this organ. Unlike invasive ductal carcinoma, there are many controversies concerning histological features of PD and the significance of the immunohistochemical characteristics of this neoplasm, which limits the optimal treatment protocols. Therefore, we decided to verify the immunohistochemical markers of PD basing on the retrospective analysis of postoperative material from 69 patients treated surgically. Microscopic examination revealed partial (7 cases) or total (62 cases) replacement of the squamous epithelium of the nipple with nests of atypical glandular cells spreading in an area ranging from 0.2 to 2.5 cm. DCIS coexisting with the PD lesions was present in all examined patients, and infiltrating carcinoma occurred in 31 (44.9%) patients. Both intraepidermal and DCIS components presented c-erbB2 overexpression. Positive estrogen and progesterone receptor staining was observed only in 7 (10.1%) and 2 (2.7%) tumours, respectively. Ki-67 proliferation index of PD cells ranged from 10% to 30%, whereas in DCIS it varied from 4% to 20%. The value of Ki-67 index exceeding 25% in the intraepidermal component of PD was associated with worse overall survival rate.}, } @article {pmid22244207, year = {2012}, author = {Rizzo, M and Linebarger, J and Lowe, MC and Pan, L and Gabram, SG and Vasquez, L and Cohen, MA and Mosunjac, M}, title = {Management of papillary breast lesions diagnosed on core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up.}, journal = {Journal of the American College of Surgeons}, volume = {214}, number = {3}, pages = {280-287}, doi = {10.1016/j.jamcollsurg.2011.12.005}, pmid = {22244207}, issn = {1879-1190}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia ; Middle Aged ; Neoplasm Grading ; Papilloma/*diagnostic imaging/*pathology/surgery ; Radiography ; Retrospective Studies ; }, abstract = {BACKGROUND: Clinical management of papillary breast lesions (PBLs) remains controversial. The objective of this study was to identify pathologic and radiologic predictors of malignancy from a large cohort of PBLs diagnosed on core-needle biopsy (CNB).

STUDY DESIGN: Retrospective review of the institutional pathology database identified all PBLs diagnosed from 2001 to 2009 and surgically excised within 6 months of diagnosis. PBLs were divided into intraductal papilloma (IDP) and IDP associated with atypical ductal or lobular hyperplasia (ADH/ALH). Surgical pathology of all lesions was reviewed and upgrade was defined as a change to a lesion of greater clinical significance, including ALH, ADH, lobular, or ductal carcinoma in situ (LCIS or DCIS), and invasive ducal carcinoma (IDC).

RESULTS: We identified 276 patients (mean age 56 years; range 23 to 88 years) with PBLs on CNB. Seventy-nine patients (28.6%) upgraded to a lesion of greater clinical significance. Of the 234 (84.7%) had IDP only, 42 (17.9%) upgraded to ADH, and 21 (8.9%) to DCIS or IDC. Of the 42 (15.3%) patients with associated ADH or ALH on CNB, 16 (38.0%) upgraded to DCIS or IDC. The majority of patients (n = 173, 62.6%) had no breast symptoms. All patients had an abnormal mammogram and/or ultrasound that prompted the CNB. Among all clinical and radiographic variables analyzed, older age alone was predictive of upgrade.

CONCLUSIONS: Frequent upgrade to a high-risk lesion or cancer is observed with IDPs diagnosed on CNB without adequate identifiable clinical and radiographic risk factors. Surgical excision should be performed for all IDPs to delineate subsequent clinical management.}, } @article {pmid22238453, year = {2012}, author = {Hsu, YH and Hsing, CH and Li, CF and Chan, CH and Chang, MC and Yan, JJ and Chang, MS}, title = {Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {188}, number = {4}, pages = {1981-1991}, doi = {10.4049/jimmunol.1102843}, pmid = {22238453}, issn = {1550-6606}, mesh = {Animals ; *Antibodies, Monoclonal/administration & dosage/immunology/pharmacology/therapeutic use ; Bone Neoplasms/metabolism/pathology/secondary ; Bone and Bones/pathology ; Breast/pathology ; Breast Neoplasms/drug therapy/*immunology/metabolism ; Carcinoma, Ductal, Breast/drug therapy/*immunology/metabolism ; Cathepsin G/biosynthesis ; Cathepsin K/biosynthesis ; Cell Line, Tumor ; Cell Movement/drug effects/immunology ; Cell Proliferation/drug effects ; Disease Progression ; Female ; Humans ; Interleukins/*biosynthesis/*immunology/pharmacology ; Matrix Metalloproteinase 12/biosynthesis ; Matrix Metalloproteinase 9/biosynthesis ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis ; *Osteolysis/drug therapy/immunology/pathology ; }, abstract = {IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.}, } @article {pmid22234886, year = {2012}, author = {Wang, S and Li, W and Liu, N and Zhang, F and Liu, H and Liu, F and Liu, J and Zhang, T and Niu, Y}, title = {Nek2A contributes to tumorigenic growth and possibly functions as potential therapeutic target for human breast cancer.}, journal = {Journal of cellular biochemistry}, volume = {113}, number = {6}, pages = {1904-1914}, doi = {10.1002/jcb.24059}, pmid = {22234886}, issn = {1097-4644}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Cell Cycle Checkpoints/genetics ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Ki-67 Antigen/genetics ; NIMA-Related Kinases ; Protein Serine-Threonine Kinases/biosynthesis/*genetics/*physiology ; RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {Nek2A (NIMA-related kinases 2A) has been known as an important centrosome regulatory factor. The aim of this study was to investigate the expression of Nek2A and the role it played in different stages of breast cancer. We detected the expression of Nek2A in both mRNA and protein levels in MCF10 cell lines including MCF-10A, MCF-10DCIS.com, MCF-10CA1a and in human breast samples which contained normal breast tissue (NBT), breast ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Our study revealed that the mRNA and protein expression of Nek2A were significantly up-regulated in MCF-10DCIS.com and MCF-10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). Our study also presented a correlation between Nek2A mRNA expression and some clinic pathological factors. We found that Nek2A mRNA expression was associated with molecular subtypes, ER, PR and Ki-67 immunoreactivity (P<0.05) in DCIS and associated with histological grade, lymph node metastasis, molecular subtypes, c-erbB-2, and Ki-67 expression (P<0.05) in IDC. In addition, we observed that ectopic expression of Nek2A in "normal" immortalized MCF-10A breast epithelial cell resulted in increased Nek2A which lead to abnormal centrosomes. Furthermore, knockdown of Nek2A in MCF-10DCIS.com could remarkably inhibit cell proliferation and induce cell cycle arrest in MCF-10DCIS.com cell line. These data suggested that Nek2A might bear a close relationship with development and progression of breast carcinoma, and highlighted its role as a novel potential biomarker for diagnosis and a possible therapeutic target for human breast cancer especially for DCIS.}, } @article {pmid22233729, year = {2011}, author = {Irabor, DO and Okolo, CA}, title = {Outcome of one hundred and forty-nine consecutive breast biopsies in Ibadan, Nigeria.}, journal = {Breast disease}, volume = {33}, number = {3}, pages = {109-114}, doi = {10.3233/BD-2010-0329}, pmid = {22233729}, issn = {1558-1551}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Biopsy ; Breast/*pathology ; Breast Neoplasms/diagnosis/*epidemiology/pathology ; Breast Neoplasms, Male/diagnosis/*epidemiology/pathology ; Female ; Fibroadenoma/diagnosis/*epidemiology/pathology ; Humans ; Male ; Mastectomy, Segmental ; Middle Aged ; Nigeria/epidemiology ; Retrospective Studies ; }, abstract = {OBJECTIVE: To study the outcomes of one hundred and forty nine consecutive breast biopsies in both male and female patients in one arm of the general surgery division of the department of surgery, university college hospital Ibadan.

METHODOLOGY: A retrospective study of the case files and histopathology reports of 149 patients who had biopsies of the breast from May 1996 to September 2004.

RESULTS: The study showed that below the age of 30 years, there was no malignancy detected in 85 breast biopsies, however as the age increased it was seen that less than one out of four biopsies were malignant when the patients were aged between 31 and 40 years, rising to one out of four biopsies for the 41-50 and 51-60 age-groups. The 61-70 yielded roughly one out of three whilst two out of three breast biopsies were malignant in the 71-80 age-groups.

CONCLUSIONS: Majority of breast lumps are benign and women have a probability of one chance in 10 that their biopsies may be malignant. However under 30 years this is unlikely. Above the age of 40 years the chance of malignancy rises to a one in four which will strongly support screening methods for women above 40 years. For record purposes, fibroadenoma is still the most common breast lesion in women under 30 years and invasive ductal carcinoma is the most common histopathological type of breast cancer in Ibadan, Nigeria.}, } @article {pmid22233382, year = {2012}, author = {Marsden, CG and Wright, MJ and Carrier, L and Moroz, K and Pochampally, R and Rowan, BG}, title = {"A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies".}, journal = {BMC cancer}, volume = {12}, number = {}, pages = {10}, pmid = {22233382}, issn = {1471-2407}, mesh = {Animals ; Biomarkers, Tumor/metabolism ; Biopsy ; Breast/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Disease Models, Animal ; Female ; Humans ; Mammary Neoplasms, Experimental/metabolism/*pathology ; Mice ; Mice, Nude ; }, abstract = {BACKGROUND: The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis.

METHODS: Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC).

RESULTS: Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 103 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples.

CONCLUSIONS: Tumorspheres isolated under defined culture conditions from patient core biopsies were tumorigenic when transplanted into the mammary fat pad of NUDE mice, and metastasized to multiple mouse organs. Micrometastases in mouse organs demonstrated a dormancy period prior to outgrowth of macrometastases. The development of macrometastases with organ-specific phenotypic distinctions provides a superior model for the investigation of organ-specific effects on metastatic cancer cell survival and growth.}, } @article {pmid22217577, year = {2012}, author = {Tamaki, K and Ishida, T and Miyashita, M and Amari, M and Ohuchi, N and Kamada, Y and Uehara, K and Tamaki, N and Sasano, H}, title = {Breast ultrasonographic and histopathological characteristics without any mammographic abnormalities.}, journal = {Japanese journal of clinical oncology}, volume = {42}, number = {3}, pages = {168-174}, doi = {10.1093/jjco/hyr197}, pmid = {22217577}, issn = {1465-3621}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: We evaluated ultrasonographic findings and the corresponding histopathological characteristics of breast cancer patients with Breast Imaging Reporting and Data System (BI-RADS) category 1 mammogram.

METHODS: We retrospectively reviewed the ultrasonographic findings and the corresponding histopathological features of 45 breast cancer patients with BI-RADS category 1 mammogram and 537 controls with mammographic abnormalities. We evaluated the ultrasonographic findings including mass shape, periphery, internal and posterior echo pattern, interruption of mammary borders and the distribution of low-echoic lesions, and the corresponding histopathological characteristics including histological classification, hormone receptor and human epidermal growth factor receptor 2 status of invasive ductal carcinoma and ductal carcinoma in situ, histological grade, mitotic counts and lymphovascular invasion in individual cases of BI-RADS category 1 mammograms and compared with those of the control group.

RESULTS: The ultrasonographic characteristics of the BI-RADS category 1 group were characterized by a higher ratio of round shape (P< 0.001), non-spiculated periphery (P= 0.021), non-interruption of mammary borders (P< 0.001) and non-attenuation (P= 0.011) compared with the control group. A total of 52.6% of low-echoic lesions were associated with spotted distribution in the BI-RADS 1 group, whereas 25.8% of low-echoic lesions were associated with spotted distribution in the control group (P= 0.012). As for histopathological characteristics, there was a statistically higher ratio of triple-negative subtype (P= 0.021), and this particular tendency was detected in histological grade 3 in the BI-RADS category 1 group (P= 0.094).

CONCLUSION: We evaluated ultrasonographic findings and the corresponding histopathological characteristics for BI-RADS category 1 mammograms and noted significant differences among these findings in this study. Evaluation of these ultrasonographic and histopathological characteristics may provide a more accurate ultrasonographic screening system for breast cancer in Japanese women.}, } @article {pmid24250973, year = {2012}, author = {Hashemzadeh, S and Aligholipour Maleki, R and Golzari, SE}, title = {The incidence of breast cancer in northwest iran (2003 -2008).}, journal = {Journal of cardiovascular and thoracic research}, volume = {4}, number = {1}, pages = {5-9}, pmid = {24250973}, issn = {2008-5117}, abstract = {INTRODUCTION: Breast Cancer is the most common cancer in Iranian women and Iranian patients are relatively young. Given that Iran has a female population of about 38 million, this corresponds to a total number of 6000 new cases of breast cancer annually. This study aims to demonstrate the characteristics of breast cancers according to pathologic records in East Azerbaijan province, Iran.

METHODS: In this retrospective cross-sectional study, 159314 pathology records of the main hospitals and pathology laboratories were observed for a period of 5 years. For each patient, sex, age, breast specimen pathology, pathological grading of malignant lesions and place of residence of patients were collected and statistically analyzed.

RESULTS: There were 12083 cancer cases; 902 of which were primary breast cancer. Breast cancer was the most common cancer in females (22.2%) but it ranks the 22(nd) in males. The annual incidence of breast cancer in women was 52.3 per 100,000. The mean age of women with breast cancer was 48.3±12.7 years (range, 16-85) and for male 54.0±13.6 years (range, 23-76). The highest frequency of malignancies was observed in the 40-49 year old age groups (34.5%). Invasive ductal carcinoma was the most common histological type diagnosed in both sexes.

CONCLUSION: In Iran, breast cancer affects women at least one decade younger than developed countries. In spite of the rare incidence of breast cancer in men, the descriptive epidemiology of this malignancy is surprisingly similar to that of women. A considerable proportion of cancers of our research were in breast which mandates a national cancer detection program encouraging women for breast self-examination and participation in screening tests to improve breast cancer care.}, } @article {pmid22207430, year = {2012}, author = {Arafah, M}, title = {Correlation of hormone receptors with Her-2 Neu protein expression and the histological grade in invasive breast cancers in a cohort of Saudi Arabia.}, journal = {Turk patoloji dergisi}, volume = {28}, number = {1}, pages = {38-43}, doi = {10.5146/tjpath.2012.01095}, pmid = {22207430}, issn = {1309-5730}, mesh = {Biomarkers, Tumor/analysis/genetics ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cohort Studies ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Grading ; Prognosis ; Receptor, ErbB-2/analysis/*biosynthesis/genetics ; Receptors, Estrogen/analysis/biosynthesis/genetics ; Receptors, Progesterone/analysis/biosynthesis/genetics ; Receptors, Steroid/*biosynthesis/genetics ; Retrospective Studies ; Saudi Arabia ; }, abstract = {OBJECTIVE: Data on Hormone Receptor and Her-2/neu expression in breast cancers from Saudi Arabia and Gulf Region is sparse. We undertook this study to describe the patterns of hormone receptor and Her-2/neu protein expression in breast carcinoma and compared them with the histological grade at a University Hospital in Riyadh.

MATERIAL AND METHOD: We conducted a retrospective study on 164 invasive ductal carcinoma of breast between the year 2002 and 2008. Immunohistochemical analysis for Estrogen and Progesterone Receptor and Her-2/neu was done in all the cases. Fluorescent in situ hybridization for Her-2/neu gene amplification was performed in all 2+ cases and few equivocal 1+ and 3+cases by immunohistochemistry. Correlation between Estrogen and Progesterone Receptor and Her-2/ neu amplification and grade of tumor was calculated.

RESULTS: The expression of Estrogen Receptor, Progesterone Receptor were significantly correlated (p < 0.001). Also, there was a significant negative correlation between expression of hormone receptor and Her-2/neu amplification. The histologic grade of the tumor was significantly correlated to the expression of both Estrogen and Progesterone Receptor. However, the relationship between Her-2/ neu amplification and grade was not significant and many of the grade III tumor were Her-2/neu negative. In addition, Her-2/neu gene amplification by fluorescent in situ hybridization was observed in 84.6% of breast cancer that were 3+ and in 18.75 % cases that were 2+ by immunohistochemistry.

CONCLUSION: Prevalence of Estrogen and Progesterone Receptor expression and Her-2/neu amplification in breast cancer in the Saudi Arabian population is similar to that reported internationally. There is a negative correlation between hormone receptors expression and Her-2/neu amplification. However not all of the high-grade breast cancers showed Her-2/neu positive status.}, } @article {pmid22203942, year = {2011}, author = {Pleşan, DM and Georgescu, M and Georgescu, CV and Pătrană, N and Nină, T and Pleşan, C}, title = {Immunohistochemical evaluation of hormone receptors with predictive value in mammary carcinomas.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {52}, number = {4}, pages = {1331-1336}, pmid = {22203942}, issn = {2066-8279}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Phenotype ; Predictive Value of Tests ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Young Adult ; }, abstract = {AIM: Immunohistochemical evaluation of hormone receptors (ER, PR) and correlation of immunohistochemical and morpho-clinical data.

MATERIALS AND METHODS: The study was performed on paraffin-embedded and HE-stained tissues originating from 100 cases of invasive mammary carcinoma. Monoclonal antibodies, anti-estrogen and anti-progesterone receptors, were used for the immunohistochemical study. The detection system was EnVision HRP and the visualization system was 3,3'-diaminobenzidine tetrahydrochloride (DAB). The evaluation of the result was performed using the Allred score.

RESULTS: The majority of the studied cases (57%) expressed both types of hormone receptors and in 32% of the cases the hormone receptors were completely absent. The rest of the cases presented a heterogeneous phenotype: 7% presented the ER-÷PR+ phenotype and 4% the ER+÷PR- phenotype. Compared with the classical phenotype (ER+÷PR-), ER+÷PR- tumors were more frequent at patients over 50-year-old. The tumors with ER+÷PR- were larger than the ER+÷PR+ and they were of the invasive ductal carcinoma type with an Allred score for ER under 6.

CONCLUSIONS: The predictive value is amplified when the ER status is correlated with the PR status because the heterogeneous phenotypes are identified, especially the ER+÷PR- phenotype, which have an aggressive behavior and the lowest response to tamoxifen therapy.}, } @article {pmid22202322, year = {2011}, author = {Sato, T and Nakagawa, T and Kuwayama, T and Oda, G and Sugimoto, H and Ishiba, T and Sugihara, K}, title = {[A case of breast cancer liver metastases responding to lapatinib and capecitabine therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {12}, pages = {2180-2182}, pmid = {22202322}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Deoxycytidine/administration & dosage/*analogs & derivatives/therapeutic use ; Fatal Outcome ; Female ; Fluorouracil/administration & dosage/*analogs & derivatives/therapeutic use ; Humans ; Lapatinib ; Liver Neoplasms/*drug therapy/secondary ; Middle Aged ; Quinazolines/administration & dosage/*therapeutic use ; }, abstract = {We report a 55-year-old female with liver metastases from breast cancer who responded to lapatinib and capecitabine combination therapy as third-line. She was diagnosed as invasive ductal carcinoma (T1cN1M0, stage IIA). Biomarker of breast cancer was negative hormone receptor (ER-, PgR-) and overexpression of HER2(HercepTest 3+). We started preoperative chemotherapy with weekly paclitaxel followed by FEC100. Then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells(pCR, grade 3). We performed her adjuvant therapy with trastuzumab after surgery. The liver metastases developed 5 months after surgery. We treated her in trasutumab combined with vinorelbine, and followed by docetaxel during one year and four months. Because liver metastases re-grew during the combination therapy with trastuzumab, we switched to lapatinib and capecitabine combination therapy. After four months of administration, abdominal CT revealed liver metastases were remarkably reduced in size. The efficacy of chemotherapy lasted for eight months.}, } @article {pmid22202269, year = {2011}, author = {Hara, Y and Sakurai, K and Fujisaki, S and Nagashima, S and Suzuki, S and Shibata, M and Tomita, R and Matsumoto, K and Enomoto, K and Amano, S}, title = {[A case of non-palpating breast cancer with huge lymph node metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {12}, pages = {2014-2016}, pmid = {22202269}, issn = {0385-0684}, mesh = {Biopsy ; Breast Neoplasms/drug therapy/*pathology/surgery ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; }, abstract = {We report a case of non-palpating breast cancer with huge lymph node metastasis. The patient was a 58-year-old woman who had a huge tumor at her right armpit. The tumor was 4 cm in diameter. Aspiration biopsy cytology for the tumor was performed. The diagnosis is Class V. Mammography showed an ill-defined mass at her right breast. Ultrasonography revealed a low echoic mass at the C area of her right breast. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 cycles of CEF (E: 60 mg/tri-weekly) plus 12 cycles of paclitaxe (l80 mg/weekly). After chemotherapy, she received muscle preserving mastectomy plus axillary lymph nodes dissection. In histopathology, there were no carcinoma cells in resected breast tissue and resected lymph nodes. Therefore, the effect of chemotherapy was diagnosed as a pathological complete response. After operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 6 years.}, } @article {pmid22202268, year = {2011}, author = {Suzuki, S and Sakurai, K and Nagashima, S and Fujisaki, S and Shibata, M and Tomita, R and Hara, Y and Matsumoto, K and Enomoto, K and Amano, S}, title = {[Surgical resection for elderly patient with skin invasion of breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {12}, pages = {2011-2013}, pmid = {22202268}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Biopsy ; Breast Neoplasms/pathology/*surgery ; Female ; Humans ; Neoplasm Invasiveness ; Skin Neoplasms/secondary/*surgery ; Tomography, X-Ray Computed ; }, abstract = {We report a locally advanced elderly breast carcinoma with skin invasion. The patient was a 96-year-old woman who had a breast lump. The palpable tumor was 3 .5 cm in diameter. Ultrasonography revealed a low echoic mass. A core needle biopsy for the breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesteron receptor, and negative for HER2/neu protein expression. She underwent a tumorectomy including the cancer invasive skin by local anesthesia. Because her respiratory function was unbearable to perform a muscle-preserving mastectomy with general anesthesia. The surgical margins of the resected specimen were negative. The clinicopathological stage, according to the UICC-pTNM classification, was Stage III C (T4b, N0, M0). After the operation, she was administered aromatase inhibitor. The patient has been well and remained disease-free during a follow-up period of 3 years. The surgical excision with local anesthesia was useful for locally advanced super senior breast cancer patients who were impossible to perform general anesthesia by various kinds of factors.}, } @article {pmid22202267, year = {2011}, author = {Inoue, T and Nishi, T and Yoshida, T and Yayoi, E and Sawai, Y and Yamazaki, M}, title = {[Local control of advanced breast cancer with mohs'paste].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {12}, pages = {2008-2010}, pmid = {22202267}, issn = {0385-0684}, mesh = {Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; }, abstract = {We report two cases of primary advanced breast cancer that was locally controlled by using Mohs'paste. CASE 1: A 70- year-old woman was suffering massive exudates and offensive smell from her right giant breast tumor. Histopathological examination showed an invasive ductal carcinoma. However, she didn't have distant metastases. The patient received chemotherapy and the breast tumor has been fixed using Mohs'paste, and dissected. The giant tumor became flat and dry, so we could perform a radical operation. Then, she had contra-lateral axillary lymph node metastases. We performed a resection of left axillary lymph node and radiation therapy. After two years, we have not found a new lesion. CASE 2: A 54-year- old woman with right local advanced breast cancer discharged massive exudates and oozed blood. Histopathologically, she had an invasive ductal carcinoma. Moreover, she had lung and contra-lateral axillary lymph node metastases. She received chemotherapy and the breast tumor has been fixed using Mohs'paste, and dissected. The bleeding and exudates stopped almost completely, and the breast tumor became flat and dry. Both patients had experienced a mild pain, but their QOL improved remarkably. It is suggested that the patient with local advanced breast cancer may be controlled by using Mohs' paste.}, } @article {pmid22191029, year = {2011}, author = {Rozentsvayg, E and Carver, K and Borkar, S and Mathew, M and Enis, S and Friedman, P}, title = {Surgical excision of benign papillomas diagnosed with core biopsy: a community hospital approach.}, journal = {Radiology research and practice}, volume = {2011}, number = {}, pages = {679864}, pmid = {22191029}, issn = {2090-195X}, abstract = {Our goal was to assess the value of surgical excision of benign papillomas of the breast diagnosed on percutaneous core biopsy by determining the frequency of upgrade to malignancies and high risk lesions on a final surgical pathology. We reviewed 67 patients who had biopsies yielding benign papilloma and underwent subsequent surgical excision. Surgical pathology of the excised lesions was compared with initial core biopsy pathology results. 54 patients had concordant benign core and excisional pathology. Cancer (ductal carcinoma in situ and invasive ductal carcinoma) was diagnosed in five (7%) patients. Surgery revealed high-risk lesions in 8 (12%) patients, including atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Cancer and high risk lesions accounted for 13 (19%) upstaging events from benign papilloma diagnosis. Our data suggests that surgical excision is warranted with core pathology of benign papilloma.}, } @article {pmid22186257, year = {2012}, author = {Hsing, CH and Cheng, HC and Hsu, YH and Chan, CH and Yeh, CH and Li, CF and Chang, MS}, title = {Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {18}, number = {3}, pages = {713-725}, doi = {10.1158/1078-0432.CCR-11-1532}, pmid = {22186257}, issn = {1557-3265}, mesh = {Animals ; Biomarkers, Tumor/*analysis ; Blotting, Western ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cell Line, Tumor ; Cell Separation ; Disease Progression ; Female ; Flow Cytometry ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Interleukin-10/*biosynthesis ; Interleukins/*biosynthesis ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Treatment Outcome ; Up-Regulation ; }, abstract = {PURPOSE: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome.

EXPERIMENTAL DESIGN: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19-overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured.

RESULTS: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19-overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung.

CONCLUSIONS: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer.}, } @article {pmid22175904, year = {2011}, author = {Pula, B and Jethon, A and Piotrowska, A and Gomulkiewicz, A and Owczarek, T and Calik, J and Wojnar, A and Witkiewicz, W and Rys, J and Ugorski, M and Dziegiel, P and Podhorska-Okolow, M}, title = {Podoplanin expression by cancer-associated fibroblasts predicts poor outcome in invasive ductal breast carcinoma.}, journal = {Histopathology}, volume = {59}, number = {6}, pages = {1249-1260}, doi = {10.1111/j.1365-2559.2011.04060.x}, pmid = {22175904}, issn = {1365-2559}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Female ; Fibroblasts/*metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Glycoproteins/analysis/*biosynthesis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {AIMS: It has recently been shown that podoplanin, a mucin-type glycoprotein, is expressed by cancer cells and cancer-associated fibroblasts (CAFs), and promotes cancer cell migration and invasiveness. The biological role of podoplanin expression in tumour stroma of invasive ductal carcinoma of the breast (IDC) has not been determined.

METHODS AND RESULTS: Podoplanin expression was analysed in 117 cases of IDC and 27 cases of fibrocystic change, as well as in breast cancer cell lines, with the use of immunohistochemistry and real-time polymerase chain reaction. In 82.1% of analysed tumours, podoplanin was found only in CAFs. Only two of 117 IDC cases (1.7%) were characterized by expression of this glycoprotein in cancer cells. None of the fibrocystic changes or stroma surrounding normal ducts showed podoplanin expression. Podoplanin-positive CAFs correlated with tumour size (P = 0.0125), grade of malignancy (P = 0.0058), lymph node metastasis (P = 0.0149), lymphovascular invasion (LVI) (P = 0.0486) and Ki67 expression in cancer cells (P = 0.0128). High-level podoplanin expression (>50% of positive stroma) in the tumour stroma was significantly associated with a negative oestrogen status (P = 0.0201). Univariate, but not multivariate, analysis showed that podoplanin expression by CAFs was associated with poor patient outcome (P = 0.0202).

CONCLUSIONS: Our results suggest that podoplanin expression by CAFs could be an unfavourable prognostic marker for IDC.}, } @article {pmid22172957, year = {2012}, author = {Fernandez-Flores, A and Valerdiz, S and Crespo, LG and Rodriguez-Cernuda, P}, title = {Areolar sebaceous hyperplasia with underlying primary duct carcinoma of the breast in a woman with Donohue syndrome (leprechaunism).}, journal = {The American Journal of dermatopathology}, volume = {34}, number = {2}, pages = {e15-8}, doi = {10.1097/DAD.0b013e318231311a}, pmid = {22172957}, issn = {1533-0311}, mesh = {Adult ; Breast Neoplasms/*complications/pathology ; Carcinoma, Ductal, Breast/*complications/pathology ; Donohue Syndrome/*complications/pathology ; Female ; Humans ; Hyperplasia/pathology ; Immunohistochemistry ; Nipples/*pathology ; Sebaceous Glands/*pathology ; }, abstract = {Areolar hyperplasia is only reported when exaggerated, and even so, exaggerated areolar sebaceous hyperplasia is rare. We have recently seen a case of areolar sebaceous hyperplasia in a 32-year-old woman with Donohue syndrome (leprechaunism), who also had an invasive ductal carcinoma in the same breast. The patient showed typical "elfin-like" face with wide nostrils and thick lips, large and low-set ears, and dysplastic nails. The areola showed a yellowish thickened plaque of 5-cm diameter that corresponded to a hyperplasia of the sebaceous glands. Immunohistochemistry for the mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) was performed on the sebaceous hyperplasia and on the breast carcinoma, and no lack of expression of the markers was evidenced. We have found no other reported case of areolar sebaceous hyperplasia either in cases of breast carcinoma or in cases of leprechaunism.}, } @article {pmid22151989, year = {2011}, author = {Ma, D and Dong, X and Zang, S and Ma, R and Zhao, P and Guo, D and Dai, J and Chen, F and Ye, J and Ji, C}, title = {Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {7}, number = {4}, pages = {385-391}, doi = {10.1111/j.1743-7563.2011.01433.x}, pmid = {22151989}, issn = {1743-7563}, mesh = {Biomarkers, Tumor/biosynthesis/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; China ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Receptors, Notch/*biosynthesis/genetics/metabolism ; Signal Transduction ; }, abstract = {AIMS: Notch signaling molecules play crucial roles in cell proliferation and apoptosis, yet their function in breast cancer remains unclear.

METHODS: Samples and clinical data from 62 breast cancer patients were collected. After total RNA isolation, reverse transcription polymerase chain reaction was applied to analyze the expression of Notch receptors (Notch1, Notch3 and Notch4) and ligands (DLL4 and JAG1), and their clinical association. Immunohistochemical analysis was used to detect the intracellular domain of Notch1 (Notch1-IC) expression.

RESULTS: Notch1 was the dominant receptor while DLL4 was the dominant ligand. The Notch molecules expression pattern for infiltrating ductal carcinoma (IDC) was similar to that for infiltrating lobular carcinoma (ILC) except for JAG1, while Notch1 standard coefficients in ILC were statistically higher than that in IDC. Immunohistochemical results showed that Notch1-IC protein expression paralleled the mRNA level. Breast cancer patients' clinical parameters suggested that Notch1 expression was higher in stage II disease and lower in more advanced stages. The Notch3 positive rate was higher in patients with lower levels of Notch1, and the Notch3 positive rate was lower in patients with higher levels of Notch1. No apparent correlation of Notch molecules with estrogen receptor (ER), progesterone receptor (PR) was found. Though high Notch1 and Notch3 RNA levels tended to correlate with c-erbB2 expression, no statistical significance was found.

CONCLUSION: Notch molecules are useful biomarkers in breast cancer especially for Notch1 and DLL4, and Notch1 is expressed differently in different stages of human breast cancer.}, } @article {pmid22145049, year = {2011}, author = {Jung, HJ and Park, JY and Jeon, HS and Kwon, TH}, title = {Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells.}, journal = {PloS one}, volume = {6}, number = {12}, pages = {e28492}, pmid = {22145049}, issn = {1932-6203}, mesh = {Aquaporin 5/antagonists & inhibitors/genetics/*metabolism ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*secondary ; *Cell Movement ; *Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Indicators and Reagents/pharmacology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Osmosis/drug effects ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Real-Time Polymerase Chain Reaction ; Sorbitol/pharmacology ; Stress, Physiological/drug effects ; Tumor Cells, Cultured ; }, abstract = {Aquaporin (AQP) is a family of transmembrane proteins for water transport. Recent studies revealed that AQPs are likely to play a role in tumor progression and invasion. We aimed to examine the potential role of AQP5 in the progression of human breast cancer cells. Expression of AQP5 mRNA and protein was seen in human breast cancer cell line (both MCF7 and MDA-MB-231) by RT-PCR and immunoblotting analysis. Immunoperoxidase labeling of AQP5 was observed at ductal epithelial cells of human breast tissues. In benign tumor, AQP5 labeling was mainly seen at the apical domains of ductal epithelial cells. In contrast, in invasive ductal carcinoma, prominent AQP5 labeling was associated with cancer cells, whereas some ducts were unlabeled and apical polarity of AQP5 in ducts was lost. Cell proliferation (BrdU incorporation assay) and migration of MCF7 cells were significantly attenuated by lentivirus-mediated AQP5-shRNA transduction. Hyperosmotic stress induced by sorbitol treatment (100 mM, 24 h) reduced AQP5 expression in MCF7 cells, which was also associated with a significant reduction in cell proliferation and migration. Taken together, prominent AQP5 expression in breast cancer cells with the loss of polarity of ductal epithelial cells was seen during the progression of breast carcinoma. shRNA- or hyperosmotic stress-induced reduction in AQP5 expression of MCF7 cells was associated with significantly reduced cell proliferation and migration. In conclusion, AQP5 overexpression is likely to play a role in cell growth and metastasis of human breast cancer and could be a novel target for anti-breast cancer treatment.}, } @article {pmid22141605, year = {2011}, author = {Seow, JH and Metcalf, C and Wylie, E}, title = {Nipple discharge in a screening programme: imaging findings with pathological correlation.}, journal = {Journal of medical imaging and radiation oncology}, volume = {55}, number = {6}, pages = {577-586}, doi = {10.1111/j.1754-9485.2011.02294.x}, pmid = {22141605}, issn = {1754-9485}, mesh = {Adult ; Aged ; Aged, 80 and over ; Australia/epidemiology ; Breast Neoplasms/*diagnostic imaging/*epidemiology/pathology ; Comorbidity ; Female ; Humans ; Mammography/*statistics & numerical data ; Mass Screening/*statistics & numerical data ; Middle Aged ; Nipples/*diagnostic imaging/*metabolism ; Prevalence ; Risk Assessment ; Risk Factors ; }, abstract = {BreastScreen Australia provides free mammographic screening for asymptomatic women over the age of 40, targeting women aged 50-69. Occasionally women will present to screening programmes with a history of nipple discharge, which is uncommonly associated with significant underlying breast disease. Seventy-six women with a history of nipple discharge were recalled to BreastScreen Western Australia assessment centres from 2004 to 2008, of whom 72 were recalled primarily for their symptoms. Thirty-six of these patients had pathology investigations, including 18 nipple discharge smears, 17 fine needle aspirations, 11 core biopsies and eight surgical biopsies or therapeutic resections. The biopsies found 11 intraduct papillomas and one invasive ductal carcinoma with ductal carcinoma in situ. Fourteen patients had imaging findings consistent with benign mammary duct ectasia. Our findings confirm that the presentation of nipple discharge in a screening programme is uncommonly associated with significant breast disease, and present representative cases of the radiological findings with pathological correlation of benign and malignant causes including mammary duct ectasia, intraduct papillomas, multiple papillomas, invasive ductal carcinoma and ductal carcinoma in situ.}, } @article {pmid22128125, year = {2012}, author = {Choi, SY and Chang, YW and Park, HJ and Kim, HJ and Hong, SS and Seo, DY}, title = {Correlation of the apparent diffusion coefficiency values on diffusion-weighted imaging with prognostic factors for breast cancer.}, journal = {The British journal of radiology}, volume = {85}, number = {1016}, pages = {e474-9}, pmid = {22128125}, issn = {1748-880X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/*pathology ; Carcinoma, Intraductal, Noninfiltrating/blood supply/*pathology ; Diffusion Magnetic Resonance Imaging/methods ; Female ; Humans ; Ki-67 Antigen/metabolism ; Microvessels/pathology ; Middle Aged ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {OBJECTIVE: The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of breast cancer with prognostic factors.

METHODS: 335 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) and ductal carcinoma in situ (DCIS) who underwent breast MRI with diffusion-weighted imaging were included in this study. ADC of breast cancer was calculated using two b factors (0 and 1000 s mm(-2)). Mean ADCs of IDC NOS and DCIS were compared and evaluated. Among cases of IDC NOS, mean ADCs were compared with lymph node status, size and immunochemical prognostic factors using Student's t-test. ADC was also correlated with histological grade using the Kruskal-Wallis test.

RESULTS: Mean ADC of IDC NOS was significantly lower than that of DCIS (p<0.001). However, the mean ADC of histological grade of IDC NOS was not significantly different (p=0.564). Mean ADC of oestrogen receptor (ER)-positive or progesterone receptor (PR)-positive cancer was significantly lower than that of ER-negative or PR-negative cancer (p=0.003 vs p=0.032). Mean ADC of Ki-67 index-positive cancer was significantly lower than that of Ki-67 index-negative cancer (p=0.028). Mean ADC values of cancers with increased microvascular density (MVD) were significantly lower than those of cancer with no MVD increase (p=0.009). No correlations were observed between mean ADC value and human growth factor receptor 2 expression, tumour size and lymph node metastasis.

CONCLUSION: Low ADC value was correlated with positive expression of ER, PR, increased Ki-67 index, and increased MVD of breast cancer.}, } @article {pmid22116537, year = {2012}, author = {Lin, RS and Plevritis, SK}, title = {Comparing the benefits of screening for breast cancer and lung cancer using a novel natural history model.}, journal = {Cancer causes & control : CCC}, volume = {23}, number = {1}, pages = {175-185}, pmid = {22116537}, issn = {1573-7225}, support = {R01 CA105366/CA/NCI NIH HHS/United States ; U01 CA088248/CA/NCI NIH HHS/United States ; 1R01CA105366/CA/NCI NIH HHS/United States ; 1U01CA088248/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/diagnosis/epidemiology/*pathology/prevention & control ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology/prevention & control ; Carcinoma, Non-Small-Cell Lung/diagnosis/epidemiology/pathology/prevention & control ; Cell Growth Processes/physiology ; Early Detection of Cancer/methods ; Female ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*pathology/prevention & control ; Male ; Middle Aged ; *Models, Biological ; Neoplasm Metastasis ; SEER Program ; United States/epidemiology ; }, abstract = {To estimate the impact of early detection of cancer, knowledge of how quickly primary tumors grow and at what size they shed lethal metastases is critical. We developed a natural history model of cancer to estimate the probability of disease-specific cure as a function of tumor size, the tumor volume doubling time (TVDT), and disease-specific mortality reduction achievable by screening. The model was applied to non-small-cell lung carcinoma (NSCLC) and invasive ductal carcinoma (IDC), separately. Model parameter estimates were based on Surveillance Epidemiology and End Results (SEER) cancer registry datasets and validated on screening trials. Compared to IDC, NSCLC is estimated to have a lower probability of disease-specific cure at the same detected tumor size, shed lethal metastases at smaller sizes (median: 19 mm for IDC versus 8 mm for NSCLC), have a TVDT that is almost half as long (median: 252 days for IDC versus 134 days for NSCLC). Consequently, NSCLC is associated with a lower mortality reduction from screening at the same screen detection threshold and screening interval. In summary, using a similar natural history model of cancer, we quantify the disease-specific curability attributable to screening for breast cancer, and separately lung cancer, in terms of the TVDT and onset of lethal metastases.}, } @article {pmid22112711, year = {2011}, author = {Silva, M and Carvalho, N and Teixeira, A and Nogueira, G and Menezes, I and Ferreira, R and Maymone-Martins, F and Anjos, R}, title = {[Percutaneous embolization of coronary fistulas: a single-center experience].}, journal = {Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology}, volume = {30}, number = {12}, pages = {891-896}, doi = {10.1016/j.repc.2011.10.005}, pmid = {22112711}, issn = {0870-2551}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Coronary Artery Disease/*therapy ; Coronary Vessel Anomalies/*therapy ; Embolization, Therapeutic/*methods ; Female ; Humans ; Infant ; Male ; Middle Aged ; Vascular Fistula/*therapy ; Young Adult ; }, abstract = {INTRODUCTION: A coronary fistula is a connection between one of the coronary arteries and a cardiac chamber or great artery. It is a rare defect and usually occurs in isolation. Two-dimensional echocardiography has an important role in diagnosis but coronary or CT angiography is essential to delineate the anatomy. Surgery is the traditional therapeutic approach but percutaneous closure is now the recommended method, with excellent results and few complications in experienced centers.

METHODS: We describe our experience with percutaneous treatment of 15 coronary fistulas in 12 patients between 1996 and 2011. Eight (67%) were male and median age was 25 years. The most frequent symptoms were murmur and/or fatigue. All fistulas were congenital. Five patients (42%) had concomitant cardiac disease: pulmonary atresia with intact ventricular septum (1), patent ductus arteriosus (1), ostium secundum atrial septal defect (1), stenotic bicuspid aortic valve (1), and critical pulmonary stenosis operated in the neonatal period (1). Three patients had two fistulas, while the others had a single lesion. All fistulas were hemodynamically significant. They originated in the territory of the right coronary (10), left coronary (3) and circumflex (2), draining into the right ventricle (5), pulmonary artery (6), right atrium (2) coronary sinus (1) and left ventricle (1). Embolization materials included standard coils, controlled-release coils, microcoils (standard, GDC or IDC) and an Amplatzer(®) duct occluder.

RESULTS: Embolization was achieved in all patients. There was no mortality. One patient with a large fistula and a very small right coronary artery distally to the origin of the fistula had a right ventricular infarction. In three patients there were minor complications: inadvertent coil embolization, recovered in the same procedure (1), transient arrhythmia (1) and femoral pseudo-aneurysm (1). In a mean follow-up of 4.9 years (one month to 14 years), there were no procedure-related complications. Echocardiographic and/or angiographic control showed complete and permanent occlusion in ten patients and minimal residual flow in two patients through small collaterals with no hemodynamic significance.

CONCLUSION: Percutaneous embolization represents an effective form of treatment for selected coronary fistulas. A wide range of embolization devices must be available to ensure the best therapeutic approach.}, } @article {pmid22097094, year = {2011}, author = {Halimi, M and Aghbali, AA and Tabrizi, AD and Sahebmadarek, EO}, title = {Expression of epidermal growth factor receptor tyrosine kinase family in fine needle aspiration and permanent specimens of invasive lobular and ductal breast cancers.}, journal = {Pakistan journal of biological sciences : PJBS}, volume = {14}, number = {10}, pages = {584-589}, doi = {10.3923/pjbs.2011.584.589}, pmid = {22097094}, issn = {1028-8880}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*methods/standards ; Carcinoma, Ductal, Breast/*enzymology/*pathology ; Carcinoma, Lobular/*enzymology/*pathology ; False Negative Reactions ; False Positive Reactions ; Female ; Histocytochemistry/methods/standards ; Humans ; Iran ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; }, abstract = {Recently, the role of HER-2/Neu gene amplification has been enthusiastically investigated in breast cancer. Determining the HER-2/Neu status could be achieved by evaluating either histologic samples or cytologic specimens obtained by Fine Needle Aspiration (FNA). This study aimed at determining the concordance of HER-2/Neu expression in FNA and histologic sections. FNA samples, as well as their corresponding histologic sections of 90 cases with breast cancer were evaluated in Tabriz Sina Teaching Center in a 13-month period of time. The immunohistochemistry was employed for determining the HER-2/Neu amplification for both methods. The concordance rate and agreement were determined between the two methods. Ninety specimens of women with a mean age of 50.93 +/- 10.64 (29-84) years were assessed. There were 84 cases with invasive ductal carcinoma and 6 cases with invasive lobular carcinoma. Lymph nodes were involved in 50 cases and there were vascular and neural involvement in 40 and 35 cases, respectively. Her-2/Neu was not detected in 27 cases (30%) with weak and strong amplifications in 47 (52.2%) and 16 (17.8%) cases of FNA specimens, respectively. Her-2/Neu was not detected in 29 cases (32.2%) with weak and strong amplifications in 42 (46.7%) and 19 (21.1%) cases of histologic specimens, respectively. The concordance rate was 70% between the two methods. The agree ment was statistically significant between the two methods, as well (kappa = 0.51, p < 0.001). HER-2/neu gene amplification can be reliably estimated by immunohistochemistry on breast cancer FNAs and a good correlation has been found between this and results on histological sections.}, } @article {pmid22096760, year = {2011}, author = {Arrangoiz, R and Papavasiliou, P and Dushkin, H and Farma, JM}, title = {Case report and literature review: Metastatic lobular carcinoma of the breast an unusual presentation.}, journal = {International journal of surgery case reports}, volume = {2}, number = {8}, pages = {301-305}, pmid = {22096760}, issn = {2210-2612}, abstract = {INTRODUCTION: Invasive lobular carcinoma is the second most common type of invasive breast carcinoma (between 5% and 15%). The incidence of invasive lobular carcinoma has been increasing while the incidence of invasive duct carcinoma has not changed in the last two decades. This increase is postulated to be secondary to an increased use of combined replacement hormonal therapy. Patients with invasive lobular carcinoma tend to be slightly older than those with non-lobular invasive carcinoma with a reported mean age of 57 years compared to 64 years. On mammography, architectural distortion is more common and microcalcifications less common with invasive lobular carcinoma than invasive ductal carcinoma. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in autopsy studies varies in the literature from 6% to 18% with the most commonly affected organ being the stomach, followed by colon and rectum. Gastric lesions seem to be slightly more frequent, compared to colorectal lesions (6-18% compared to 8-12%, respectively).

PRESENTATION OF CASE: We present the case of a 70-year-old woman who was referred to our institution with a concurrent gastric and rectal cancer that on further evaluation was diagnosed as metastatic invasive lobular carcinoma of the breast. She has a stage IV clinical T3N1M1 left breast invasive lobular carcinoma (ER positive at 250, PR negative, HER-2/neu 1+ negative) with biopsy proven metastases to left axillary lymph nodes, gastric mucosa, peritoneum, rectal mass, and bone who presented with a partial large bowel obstruction. She is currently being treated with weekly intravenous paclitaxel, bevacizumab that was added after her third cycle, and she is also receiving monthly zoledronic acid. She is currently undergoing her 12-month of treatment and is tolerating it well. Discussion Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20-59 years. It accounts for 26% of all newly diagnosed cancers in females and is responsible for 15% of the cancer-related deaths in women.(9) Breast cancer is one of the most common malignancies that metastasize to the GI tract, along with melanoma, ovarian and bladder cancer.

CONCLUSION: We present one of the first reports of metastatic lobular breast cancer presenting as a synchronous rectal and gastric tumors. Metastatic lobular carcinoma of the breast is a rare entity with a wide range of clinical presentations. A high level of suspicion, repetition of endoscopic procedures, and a detailed pathological analysis is necessary for early diagnosis, which might help to avoid surgical treatment due to incorrect diagnosis. Patients with a history of breast cancer who present with new gastrointestinal lesions should have these lesions evaluated for evidence of metastasis through histopathologic evaluation and immunohistochemical analysis. Differentiating between a primary GI lesion and metastatic breast cancer will allow initiation of appropriate treatment and help prevent unnecessary operations.}, } @article {pmid22094119, year = {2012}, author = {Komar, J and Leprêtre, PM and Alberty, M and Vantorre, J and Fernandes, RJ and Hellard, P and Chollet, D and Seifert, L}, title = {Effect of increasing energy cost on arm coordination in elite sprint swimmers.}, journal = {Human movement science}, volume = {31}, number = {3}, pages = {620-629}, doi = {10.1016/j.humov.2011.07.011}, pmid = {22094119}, issn = {1872-7646}, mesh = {Acceleration ; Biomechanical Phenomena ; Efficiency/physiology ; Energy Metabolism/*physiology ; Functional Laterality/physiology ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption/physiology ; *Practice, Psychological ; Psychomotor Performance/*physiology ; Reaction Time/physiology ; Swimming/*physiology ; Videotape Recording ; }, abstract = {The purpose of this study was to analyze the changes in stroke parameters, motor organization and swimming efficiency with increasing energy cost in aquatic locomotion. Seven elite sprint swimmers performed a 6×300-m incremental swimming test. Stroke parameters (speed, stroke rate and stroke length), motor organization (arm stroke phases and arm coordination index), swimming efficiency (swimming speed squared and hand speed squared) and stroke index were calculated from aerial and underwater side-view cameras. The energy cost of locomotion was assessed by measuring oxygen consumption and blood lactate. Results showed that the increase in energy cost of locomotion was correlated to an increase in the index of coordination and stroke rate, and a decrease in stroke length (p<.05). Furthermore, indicators of swimming efficiency and stroke index did not change significantly with the speed increments (p<.05), indicating that swimmers did not decrease their efficiency despite the increase in energy cost. In parallel, an increase in the index of coordination IdC and stroke rate were observed, along with a decrease in stroke length, stroke index and hand speed squared with each increment, revealing an adaptation to the fatigue within the 300m.}, } @article {pmid22091787, year = {2012}, author = {Ein-Dor, T and Reizer, A and Shaver, PR and Dotan, E}, title = {Standoffish perhaps, but successful as well: evidence that avoidant attachment can be beneficial in professional tennis and computer science.}, journal = {Journal of personality}, volume = {80}, number = {3}, pages = {749-768}, doi = {10.1111/j.1467-6494.2011.00747.x}, pmid = {22091787}, issn = {1467-6494}, mesh = {*Adaptation, Psychological ; Adolescent ; Adult ; Anxiety/psychology ; Child ; *Emotions ; Female ; Humans ; Male ; *Object Attachment ; *Personality ; Psychological Theory ; Self Concept ; Self Report ; Students ; Tennis/*psychology ; }, abstract = {Attachment-related avoidance and anxiety have repeatedly been associated with poorer adjustment in various social, emotional, and behavioral domains. We examined 2 domains in which avoidant individuals might be better equipped than their less avoidant peers to succeed and be satisfied--professional singles tennis and computer science. These fields may reward self-reliance, independence, and the ability to work without proximal social support from loved ones. In study 1, we followed 58 professional singles tennis players for 16 months and found that scores on attachment-related avoidance predicted a higher ranking, above and beyond the contributions of training and coping resources. In study 2, we sampled 100 students and found that those who scored higher on avoidance were happier with their choice of computer science as a career than those who scored lower on avoidance. Results are discussed in relation to the possible adaptive functions of certain personality characteristics often viewed as undesirable.}, } @article {pmid22090695, year = {2011}, author = {Bhatia, A and Malhotra, G and Grover, P and Singh, N}, title = {A cytomorphological study of secretions in breast cancer.}, journal = {Journal of cytology}, volume = {28}, number = {4}, pages = {196-199}, pmid = {22090695}, issn = {0974-5165}, abstract = {BACKGROUND: Secretions are seen in a range of breast cancer that includes invasive ductal carcinoma, mucinous carcinoma and secretory carcinoma. Evaluation of the quantity and location of secretions and the contours of the cell clusters complement cell morphology could improve diagnostic cytopathological criteria.

AIM: To identify the range of breast carcinomas with secretions on fine-needle aspiration.

MATERIALS AND METHODS: A retrospective study of 160 patients with breast carcinoma was carried out. The tumors were typed by evaluating the quantity and location of secretions, cellularity and nuclear grade.

RESULTS: Secretions were seen in 16 of 160 breast carcinomas. Eleven were invasive ductal carcinoma (IDC), three were mucinous and two were secretory carcinomas. In IDC, minimal intracytoplasmic secretions were seen in 10, nuclear grades of 2 and 3 in 9, cell clusters with irregular margins in 6, and necrosis in 4. All mucinous and secretory carcinomas were nuclear grade 1. Extensive extracellular secretions and cell clusters with rounded contours were seen in mucinous carcinomas. In secretory carcinomas, the secretions were predominantly intracellular; stringy vasculature was a unique feature.

CONCLUSION: Secretions in breast cancer are seen in a range of lesions that include IDC, mucinous, and secretory carcinomas. The quantity and location of secretions in breast cancer offer clues to differentiating these.}, } @article {pmid22090465, year = {2012}, author = {Choi, BB and Shu, KS}, title = {Metaplastic carcinoma of the breast: multimodality imaging and histopathologic assessment.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {53}, number = {1}, pages = {5-11}, doi = {10.1258/ar.2011.110341}, pmid = {22090465}, issn = {1600-0455}, mesh = {Adult ; Aged ; Breast/pathology/ultrastructure ; Breast Neoplasms/*diagnosis/ultrastructure ; Carcinoma, Ductal, Breast/*diagnosis/*secondary/ultrastructure ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Metaplasia ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: Metaplastic carcinomas are ductal carcinomas that display metaplastic transformation of the glandular epithelium to non-glandular mesenchymal tissue. Metaplastic carcinoma has a poorer prognosis than most other breast cancers, so the differential diagnosis is important. Although many clinical and pathologic findings have been reported, to our knowledge, few imaging findings related to metaplastic carcinoma have been reported.

PURPOSE: To investigate whole-breast imaging findings, including mammography, sonography, MRI, and pathologic findings, including immunohistochemical studies of metaplastic carcinomas of the breast.

MATERIAL AND METHODS: We analyzed 33 cases of metaplastic carcinoma between January 2001 and January 2011. Mammography, ultrasonography, and MRI were recorded retrospectively using the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon. Immunohistochemical studies of estrogen receptor (ER), progesterone receptor (PR), p53, and C-erbB-2 were performed.

RESULTS: The most common mammographic findings were oval shape (37%), circumscribed margin (59%), and high density (74%). The most common sonographic findings were irregular shape (59.4%), microlobulated margin (41%), complex echogenicity (81%), parallel orientation (97%), and posterior acoustic enhancement (50%). Axillary lymph node metastases were noted for 25% of the sonographic examinations. On MRI, the most common findings of margin and shape were irregularity (57% and 52.4%, respectively). High signal intensity was the most common finding on T2-weighted images (57%). Immunohistochemical profile was negative for ER (91%, 29/32) and PR (81%, 26/32).

CONCLUSION: Metaplastic carcinomas might display more benign features and less axillary lymph node metastasis than IDC. High signal intensity on T2 MRI images and hormone receptor negativity would be helpful in differentiating this tumor from other breast cancers.}, } @article {pmid22086737, year = {2012}, author = {Zeng, F and Xu, G and Zhou, T and Yang, C and Wang, X and Peng, C and Zhou, H}, title = {Reduced expression of activin receptor-like kinase 7 in breast cancer is associated with tumor progression.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {4}, pages = {2519-2526}, pmid = {22086737}, issn = {1559-131X}, mesh = {Activin Receptors, Type I/analysis/*physiology ; Activins/pharmacology ; Adult ; Aged ; Breast Neoplasms/enzymology/*pathology ; Cell Line, Tumor ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Protein Serine-Threonine Kinases/genetics ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta/genetics ; }, abstract = {To explore the clinical implication of activin receptor-like kinase 7 (ALK7) expression in breast cancer, we evaluated its protein level in six kinds of human breast tissue samples, including adjacent normal tissues, adenosis, breast fibroadenoma, ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and lymph node metastases (LNM). Immunohistochemical analyses showed that ALK7 was more frequently and much more intensely expressed in adjacent normal tissues, adenosis, and fibroadenoma tissues than in malignant tissues (DCIS, IDC, and LNM). Furthermore, the ALK7 expression in primary tumors and the corresponding LNM was evaluated in parallel samples from 60 patients with IDC. Results showed that the ALK7 expression status in primary tumors and LNM was concordant in 53 patients (88%), suggesting that ALK7 expression was retained in LNM. Moreover, our results suggested that ALK7 expression inversely correlated with the tumor grade (P=0.009) and clinical stage (P=0.004) in IDC significantly. Finally, the effect of activin-ALK7 pathway on the breast cancer cell growth was elucidated, and results revealed that overexpression of ALK7 could restore the inhibitory effect of activin B on the growth of ALK7-negative breast cancer cell line, ZR-75-30. These findings provide the evidence that the reduction or lack of ALK7 expression may account for the loss of its ligand sensitivity of breast cancer cells, thereby leading to breast tumor progression.}, } @article {pmid22083518, year = {2012}, author = {Motoi, F and Egawa, S and Unno, M}, title = {Middle pancreatectomy.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {19}, number = {2}, pages = {148-151}, doi = {10.1007/s00534-011-0477-3}, pmid = {22083518}, issn = {1868-6982}, mesh = {Humans ; Minimally Invasive Surgical Procedures/*methods ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/diagnosis/*surgery ; Pancreaticojejunostomy/methods ; Suture Techniques ; Treatment Outcome ; }, abstract = {Middle pancreatectomy is parenchyma- and adjacent organ-sparing pancreatectomy indicated for small tumors located in the body, but deeply located in the gland, and therefore hard to enucleate. Others lesions including pancreatic trauma or arteriovenous malformation are also candidate targets. Invasive ductal carcinoma, even when the tumor is small enough, is not eligible because the most of these tumors show extrapancreatic invasion. After exposure of neck to body of the pancreas, middle pancreatectomy was performed by proximal and distal transection, reconstruction after Roux-Y pancreaticojejunostomy, which is the most common. This procedure is low-invasive and allow the preservation of exocrine and endocrine pancreatic function without loss of duodenal passage, however, it also has a high morbidity associated with pancreatic fistula. This article provides indications and surgical techniques with special focus on the procedure of middle pancreatectomy.}, } @article {pmid22083517, year = {2012}, author = {Takahashi, H and Ohigashi, H and Ishikawa, O}, title = {Pancreaticoduodenectomy for invasive pancreatic cancer (with video).}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {19}, number = {2}, pages = {100-108}, doi = {10.1007/s00534-011-0467-5}, pmid = {22083517}, issn = {1868-6982}, mesh = {Humans ; Mesenteric Artery, Superior/*surgery ; *Neoplasm Invasiveness ; *Pancreas/blood supply/innervation/surgery ; Pancreatic Neoplasms/pathology/*surgery ; Pancreaticoduodenectomy/*methods ; Retroperitoneal Space/*pathology ; }, abstract = {Pancreaticoduodenectomy (PD) is the only treatment option that potentially provides a cure for pancreatic head cancer. Various arrangements and modifications have been proposed to achieve pathological margin negative (R0) resection safely. In this article, we introduce a standard procedure for PD, including pancreaticogastrostomy with invagination and mattress sutures (video clip provided), for invasive ductal carcinoma of the pancreatic head, with a description of the need-to-know pitfalls for Board-certified HBP surgeons in Japan. The important points in performing PD for pancreatic cancer are: (1) While dissecting connective tissue and nerve plexus as well as lymph nodes, maintain a dissection plane to expose the surfaces of vessels or other organs to be preserved to achieve R0 resection: i.e., while dissecting the anterior surface of the inferior vena cava and the right side of the superior mesenteric artery, these vessels should be completely exposed with the connective tissue and nerve plexuses being attached to the resection side. (2) There should be early interruption of the afferent blood supply via the inferior pancreaticoduodenal artery to reduce blood loss by avoiding congestion of the pancreatic head and to increase the operative safety (video clip provided). (3) Eligibility for PD should be carefully evaluated because there are many "resectable" but not many "curable" cases. In addition, the clinical significance of various modifications of the surgical techniques used for PD are also discussed.}, } @article {pmid22083198, year = {2011}, author = {Muraoka, T and Taira, N and Shien, T and Doihara, H and Takaki, A and Miyoshi, S}, title = {[A case of the usage of entecavir to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patient].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {11}, pages = {1861-1864}, pmid = {22083198}, issn = {0385-0684}, mesh = {Antiviral Agents/*therapeutic use ; Breast Neoplasms/complications/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B/complications/*drug therapy ; Hepatitis B virus/*drug effects/physiology ; Humans ; Mammaplasty ; Middle Aged ; Neoplasm Staging ; Virus Activation/*drug effects ; }, abstract = {Hepatitis B virus(HBV)reactivation is a serious clinical problem for HBV infected patients, and one of its possible causes is chemotherapy for malignant disease. At the onset of active hepatitis, planned chemotherapy should be discontinued and acute or fetal fulminant hepatitis must be induced in some cases. Therefore, it is desirable to prevent virus reactivation during chemotherapy in HBV-positive patients. We report a case in which adjuvant chemotherapy for a breast cancer patient was accomplished safely by using entecavir. The patient was a 48-year-old woman with breast cancer whose HBV infection had been pointed out when she was 20 years old. Breast reconstruction was performed, followed by mastectomy. Pathological findings were invasive ductal carcinoma, three positive nodes, estrogen and progesterone receptor-positive, and HER2-negative. An adjuvant chemotherapy with anthracycline followed by taxane was planned. Blood chemistry revealed the seroconversion of HBV and the quantity of HBV-DNA was 2. 8 log copies/mL. Administration of the anti-virus agent, entecavir, was started three weeks before chemotherapy. The HBV-DNA was decreased under the titer of detection and no re-increase in HBV-DNA was found during chemotherapy. Planned chemotherapy was accomplished safely without HBV reactivation.}, } @article {pmid22080244, year = {2012}, author = {Morrogh, M and Andrade, VP and Giri, D and Sakr, RA and Paik, W and Qin, LX and Arroyo, CD and Brogi, E and Morrow, M and King, TA}, title = {Cadherin-catenin complex dissociation in lobular neoplasia of the breast.}, journal = {Breast cancer research and treatment}, volume = {132}, number = {2}, pages = {641-652}, pmid = {22080244}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/pathology ; Cadherins/*analysis/genetics ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/genetics/pathology ; Carcinoma, Lobular/*chemistry/genetics/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Complex and Mixed/*chemistry/genetics/pathology ; New York City ; Nuclear Proteins/analysis ; Phosphorylation ; Prognosis ; Prospective Studies ; Protein Binding ; Snail Family Transcription Factors ; Transcription Factors/analysis ; Twist-Related Protein 1/analysis ; alpha Catenin/*analysis/genetics ; beta Catenin/*analysis/genetics ; }, abstract = {E-cadherin (E-CD) inactivation with loss of E-CD-mediated cell adhesion is the hallmark of lesions of the lobular phenotype. E-CD is typically absent by immunohistochemistry in both lobular carcinoma in situ (LCIS) and invasive lobular lesions, suggesting it occurs early in the neoplastic process. In laboratory models, downstream post-transcriptional modifiers such as TWIST and SNAIL contribute to the dissociation of the intracellular component of the cadherin-catenin complex (CCC), resulting in tumor progression and invasion. We hypothesized that complete CCC dissociation may play a role in lobular neoplasia progression. Here we explore the relationship between loss of E-CD and dissociation of the CCC in pure LCIS and LCIS associated with invasive cancer. Fresh-frozen tissues were obtained from 36 patients undergoing mastectomy for pure LCIS (n = 11), LCIS with ILC (n = 18) or LCIS with IDC (n = 7). Individual lesions were subject to laser-capture microdissection and gene-expression analysis (Affymetrix HG-U133A 2.0). Immunohistochemistry for ER,PR,HER2, E-CD,N-CD,α-,β-, and phosphoβ-catenin, TWIST, and SNAIL were evaluated in normal, in situ, and invasive components from matched formalin-fixed paraffin-embedded samples (n = 36). CCC-dissociation was defined as negative membranous E-CD, α- and β-catenin expression. E-CD was negative in all LCIS and ILC lesions, and positive in all normal and IDC lesions. Membranous α and β-catenin expressions decreased with the transition from LCIS to ILC (pure LCIS 82%; LCIS w/ILC 28%; ILC 0%), while TWIST expression increased (pure LCIS low; LCIS w/ILC moderate; ILC high). Gene expression paralleled IHC-staining patterns with a stepwise downregulation of E-CD, α and β-catenins from normal to LCIS to invasive lesions, and increasing expression of TWIST from normal to LCIS to ILC. Loss of E-CD expression is an early event in lobular neoplasia. Decreasing membranous catenin expression in tandem with increasing levels of TWIST across the spectrum of lobular lesions suggests that CCC dissociation is a progressive process.}, } @article {pmid22070025, year = {2011}, author = {Li, CX and Hussain, A and Kamali, A}, title = {A hip simulator study of metal-on-metal hip joint device using acetabular cups with different fixation surface conditions.}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine}, volume = {225}, number = {9}, pages = {877-887}, doi = {10.1177/0954411911411604}, pmid = {22070025}, issn = {0954-4119}, mesh = {Acetabulum ; Durapatite ; Hip Joint ; *Hip Prosthesis ; Humans ; Materials Testing/*methods ; Metals ; Microscopy, Electron, Scanning ; Prosthesis Design ; Reproducibility of Results ; Surface Properties ; }, abstract = {In vitro wear data for hip joint devices reported in the literature vary in a wide range from one simulator study to another sometimes for the same type of device tested under identical physiological testing conditions. We hypothesized that non-bearing surface condition of the testing components could be an important factor affecting the simulator wear results. To confirm this hypothesis, fifteen 50 mm metal-on-metal hip resurfacing devices with identical bearing specifications were tested in a ProSim hip wear simulator for 5 million cycles. The heads were standard Birmingham Hip Resurfacing (BHR) heads; whilst the pairing acetabular cups were identical to the standard BHR cup except their different back surface conditions, including: (a) off-the-shelf products after removing the hydroxyapatite (HA) coating; (b) semi-finished products without HA coating; and (c) purposely-made cups without cast-in beads and HA coating. Results showed that the different back surfaces of the cups used indeed caused significantly large variations in the gravimetrically measured wear loss. We postulated that materials loss from the non-bearing surface of the testing components could contribute to the gravimetrically measured wear loss during a wear simulator test both directly and indirectly. The results presented in this paper pertain to In vitro wear simulator study and have little clinical relevance to the performance of any implant in vivo.}, } @article {pmid22068691, year = {2012}, author = {Brustein, VP and Cavalcanti, CL and de Melo-Junior, MR and Correia, MT and Beltrão, EI and Carvalho, LB}, title = {Chemiluminescent detection of carbohydrates in the tumoral breast diseases.}, journal = {Applied biochemistry and biotechnology}, volume = {166}, number = {2}, pages = {268-275}, doi = {10.1007/s12010-011-9422-9}, pmid = {22068691}, issn = {1559-0291}, mesh = {Biomarkers/chemistry/metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Carbohydrate Metabolism ; Carbohydrates/*analysis/chemistry ; Carcinoma, Ductal, Breast/diagnosis/metabolism/pathology ; Concanavalin A/metabolism ; Female ; Fibroadenoma/diagnosis/metabolism/pathology ; Humans ; Luminescent Measurements/*methods ; Middle Aged ; Peanut Agglutinin/metabolism ; }, abstract = {Nowadays, there is an increase of investigations into the fibroadenoma, mainly because some studies have shown that the occurrence of fibroadenoma is linked to an increased risk of developing breast carcinoma. Currently, the chemiluminescence biomarkers are applied for validation methods and screening. Here, a lectin chemiluminescence is proposed as new histochemistry method to identify carbohydrates in mammary tumoral tissues. The lectins concanavalin A (Con A) and peanut agglutinin (PNA) conjugated to acridinium ester were used to characterize the glycocode of breast tissues: normal, fibroadenoma, and invasive duct carcinoma (IDC). The lectin chemiluminescence expressed in relative light units (RLU) was higher in fibroadenoma and IDC than in normal tissue for both lectins tested. The relationship RLU emission versus tissue area described a linear and hyperbolic curve for IDC and fibroadenoma, respectively, using Con A whereas hyperbolic curves for both transformed tissues using PNA. RLU was abolished by inhibiting the interaction between tissues and lectins using their specific carbohydrates: methyl-α-D: -mannoside (Con A) and galactose (PNA). The intrinsic fluorescence emission did not change with combination of the lectins (Con A/PNA) to the acridinium ester for hydrophobic residues. These results represent the lectin chemiluminescence as an alternative of histochemistry method for tumoral diagnosis in the breast.}, } @article {pmid22067528, year = {2011}, author = {Hua, X and Yu, L and Huang, X and Liao, Z and Xian, Q}, title = {Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {111}, pmid = {22067528}, issn = {1746-1596}, mesh = {Biomarkers, Tumor/*analysis/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Calcium-Binding Proteins/analysis/biosynthesis ; Carcinoma in Situ/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Endopeptidases ; Female ; Fibroblasts/pathology ; Gelatinases/analysis/*biosynthesis ; Humans ; Immunohistochemistry ; Membrane Proteins/analysis/*biosynthesis ; Microfilament Proteins/analysis/biosynthesis ; Neoplasm Invasiveness/*diagnosis ; Serine Endopeptidases/analysis/*biosynthesis ; }, abstract = {BACKGROUND: Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion.

METHODS: 349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted.

RESULTS: Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%.

CONCLUSIONS: This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.}, } @article {pmid22064040, year = {2012}, author = {Hida, T and Yoneta, A and Nishizaka, T and Ohmura, T and Suzuki, Y and Kameshima, H and Yamashita, T}, title = {Pigmented mammary Paget's disease mimicking melanoma: report of three cases.}, journal = {European journal of dermatology : EJD}, volume = {22}, number = {1}, pages = {121-124}, doi = {10.1684/ejd.2011.1580}, pmid = {22064040}, issn = {1167-1122}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/pathology/surgery ; Dermoscopy ; Diagnosis, Differential ; Female ; Humans ; Mastectomy ; Melanoma/diagnosis/*pathology ; Paget's Disease, Mammary/*diagnosis/pathology/surgery ; Skin Neoplasms/diagnosis/*pathology ; }, abstract = {Pigmented mammary Paget's disease (PMPD) is a rare subtype of mammary Paget's disease. The differential diagnosis of PMPD and melanoma is difficult clinically and sometimes histopathologically. Here we present three cases of PMPD with a variable-sized lesion. All cases showed an irregular-shaped black-brown macule, one of which was accompanied by nipple retraction. Dermoscopically, all cases showed reticular pigmentation with or without irregular black dots, regression structures and streaks, which were indistinguishable from those of melanoma. In all but one of the cases, preoperative examinations confirmed the presence of a subcutaneous mammary lesion. All patients underwent a total mastectomy with the histopathological results indicating invasive ductal carcinoma. These cases emphasize how difficult it is to distinguish PMPD from melanoma. Dermoscopic features also mimic those of melanoma, but the reticular pigmentation seen in all cases could be a feature specific to PMPD. For suspicious cases, histopathological assessment using immunohistochemistry is highly recommended.}, } @article {pmid22057904, year = {2011}, author = {Shankayi, Z and Firoozabadi, SM}, title = {Tumor growth inhibited by low-voltage amplitude and 5-kHz frequency electrochemotherapy.}, journal = {The Journal of membrane biology}, volume = {244}, number = {3}, pages = {121-128}, pmid = {22057904}, issn = {1432-1424}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Bleomycin/therapeutic use ; Carcinoma, Ductal/drug therapy ; Electrochemotherapy/*methods ; Female ; Mice ; Mice, Inbred BALB C ; Neoplasms/*drug therapy ; }, abstract = {The most important unpleasant sensation of electrochemotherapy is muscle contraction. One of the causes of this discomfort is electrochemotherapy in the low-frequency range (1 Hz). To resolve this problem, there are two solutions: first, increasing the repetition frequency of electric pulses above the tetanic frequency and, second, reducing the voltage amplitude. This study examines the antitumor effectiveness of treatment using low electric fields and high frequency in the presence and absence of chemotherapeutic agents. High-voltage amplitude electrochemotherapy was performed by eight pulses, at 1,000 V/cm, of 100-μs duration at 1-Hz and 5-kHz repetition frequency. In the low-voltage amplitude protocol, 4,000 pulses, of 100-μs duration at 5-kHz repetition frequency with 70, 100 and 150 V/cm were delivered to invasive ductal carcinoma tumors after intratumoral injection of bleomycin. Our data demonstrate significant differences in tumor volumes and the curability rate between mice treated by 70 V/cm compared to other groups. Electrochemotherapy, which is specified by a higher repetition frequency of electric pulses (5 kHz) and low voltage, inhibits tumor growth. This protocol has a comparable effect to 1-Hz pulse repetition electric pulses with high voltage. Based on these results, the 4,000 pulses of 70 V/cm with 5-kHz frequency are most effective. This protocol demonstrates inhibition of tumor growth without any need for drug administration.}, } @article {pmid22055399, year = {2012}, author = {Yakirevich, E and Samkari, A and Holloway, MP and Lu, S and Singh, K and Yu, J and Fenton, MA and Altura, RA}, title = {Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer.}, journal = {Human pathology}, volume = {43}, number = {6}, pages = {865-873}, doi = {10.1016/j.humpath.2011.07.014}, pmid = {22055399}, issn = {1532-8392}, mesh = {Acetylation ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins/*biosynthesis/genetics ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Survivin ; Tissue Array Analysis ; }, abstract = {Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy.}, } @article {pmid22053985, year = {2011}, author = {Bi, X and Hameed, M and Mirani, N and Pimenta, EM and Anari, J and Barnes, BJ}, title = {Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis.}, journal = {Breast cancer research : BCR}, volume = {13}, number = {6}, pages = {R111}, pmid = {22053985}, issn = {1465-542X}, mesh = {Animals ; Apoptosis/genetics/radiation effects ; Breast Neoplasms/*genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Chemokine CXCL12/metabolism ; Chemotaxis/genetics ; DNA Damage ; Down-Regulation/genetics ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Interferon Regulatory Factor-1/genetics/metabolism ; Interferon Regulatory Factors/*genetics/metabolism ; Lymph Nodes/metabolism/pathology ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Staging ; Radiation Tolerance/genetics ; Receptors, CXCR4/genetics/metabolism ; Transcription, Genetic ; }, abstract = {INTRODUCTION: New signaling pathways of the interleukin (IL) family, interferons (IFN) and interferon regulatory factors (IRF) have recently been found within tumor microenvironments and in metastatic sites. Some of these cytokines stimulate while others inhibit breast cancer proliferation and/or invasion. IRFs, a family of nine mammalian transcription factors, have multiple biologic functions that when dysregulated may contribute to tumorigenesis; most well-known are their roles in regulating/initiating host immunity. Some IRF family members have been implicated in tumorigenesis yet little is still known of their expression in primary human tumors or their role(s) in disease development/progression. IRF5 is one of the newer family members to be studied and has been shown to be a critical mediator of host immunity and the cellular response to DNA damage. Here, we examined the expression of IRF5 in primary breast tissue and determined how loss of expression may contribute to breast cancer development and/or progression.

METHODS: Formalin-fixed paraffin-embedded archival breast tissue specimens from patients with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were examined for their expression of IRF1 and IRF5. Knockdown or overexpression of IRF5 in MCF-10A, MCF-7 and MDA-MB-231 mammary epithelial cell lines was used to examine the role of IRF5 in growth inhibition, invasion and tumorigenesis.

RESULTS: Analysis of IRF expression in human breast tissues revealed the unique down-regulation of IRF5 in patients with different grades of DCIS and IDC as compared to IRF1; loss of IRF5 preceded that of IRF1 and correlated with increased invasiveness. Overexpression of IRF5 in breast cancer cells inhibited in vitro and in vivo cell growth and sensitized them to DNA damage. Complementary experiments with IRF5 siRNAs made normal mammary epithelial cells resistant to DNA damage. By 3-D culture, IRF5 overexpression reverted MDA-MB-231 to normal acini-like structures; cells overexpressing IRF5 had decreased CXCR4 expression and were insensitive to SDF-1/CXCL12-induced migration. These findings were confirmed by CXCR4 promoter reporter assays.

CONCLUSIONS: IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential.}, } @article {pmid22052326, year = {2012}, author = {Johnson, CE and Gorringe, KL and Thompson, ER and Opeskin, K and Boyle, SE and Wang, Y and Hill, P and Mann, GB and Campbell, IG}, title = {Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma.}, journal = {Breast cancer research and treatment}, volume = {133}, number = {3}, pages = {889-898}, doi = {10.1007/s10549-011-1835-1}, pmid = {22052326}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Chromosome Aberrations ; *DNA Copy Number Variations ; Disease Progression ; Female ; Humans ; Neoplasm Invasiveness/genetics ; Recurrence ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR.}, } @article {pmid22051146, year = {2011}, author = {Li, W and Yang, D and Wang, S and Guo, X and Lang, R and Fan, Y and Gu, F and Zhang, X and Niu, Y and Yan, X and Fu, L}, title = {Increased expression of CD146 and microvessel density (MVD) in invasive micropapillary carcinoma of the breast: Comparative study with invasive ductal carcinoma-not otherwise specified.}, journal = {Pathology, research and practice}, volume = {207}, number = {12}, pages = {739-746}, doi = {10.1016/j.prp.2011.09.009}, pmid = {22051146}, issn = {1618-0631}, mesh = {Adult ; Aged ; Breast/metabolism/pathology ; Breast Neoplasms/*blood supply/*metabolism/pathology ; CD146 Antigen/analysis/genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*metabolism/pathology ; Carcinoma, Papillary/*blood supply/*metabolism/pathology ; Endothelial Cells/metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Microvessels/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast, and is characterized by a high metastatic potential and an aggressive clinical course. Studies of CD146 expression and function in breast cancer remain scarce. The aim of this study was to evaluate the role of CD146 and microvessel density (MVD) in breast IMPC. CD146 mRNA expression and immunohistochemistry for CD146 and MVD measured by CD31 were assessed in 82 cases of IMPC and 137 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The mRNA level of CD146 in cancer specimens was higher in IMPC than in IDC-NOS. CD146 expression in tumor cells was up-regulated in IMPC as compared with that in IDC-NOS, and was positively correlated with histological grade, ER, PR status, and P53 expression in IMPC and IDC-NOS. CD146 expression in vascular endothelial cells was significantly higher than that in IDC, and was positively correlated with tumor progression in IMPC and IDC-NOS. MVD in IMPC was significantly higher than that in IDC. CD146 expression in tumor cells was positively correlated with that in vascular endothelial cells of IMPC and IDC-NOS. The association of CD146 expression with MVD and its correlation with progression in breast carcinoma indicated that CD146 is a potentially useful prognostic marker for breast cancer. CD146 could be a new drug target in the treatment of breast cancer.}, } @article {pmid22046796, year = {2011}, author = {Rugină, VG and Mihalcea, D and Pricop, F}, title = {[The lymph nodes status--prognostic factor in breast cancer].}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {115}, number = {3}, pages = {839-844}, pmid = {22046796}, issn = {0048-7848}, mesh = {Adult ; Axilla ; Breast Neoplasms/mortality/*pathology/*surgery ; Carcinoma, Ductal, Breast/mortality/*pathology/*surgery ; Female ; Humans ; Kaplan-Meier Estimate ; *Lymph Node Excision ; Lymph Nodes/*pathology ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Romania/epidemiology ; Survival Rate ; }, abstract = {AIM: The assessment of the survival rate according to axillary lymph nodes status in patients diagnosed with breast cancer.

MATERIAL AND METHODS: The study group included 206 women, treated in the 4th Obstetrics and Gynecology Clinic during 2002-2005. All patients were treated surgically with lymph nodes dissection. The analyzed variables included clinical and morphological features of both primary tumor and axillary lymph nodes. We have evaluated 5 years survival in relation to positivity and number of dissected lymph nodes. In order to determine the prognostic value of evaluated variables we have used Kaplan Meir method.

RESULTS: 77.7% of all patients were aged between 40 and 49 years old and 62.6% of them presented stage II tumors. Invasive ductal carcinoma was the most frequent histologic type (79.12%) and 71.2% of tumors were moderated of poorly differentiated, lymph nodes invasion being presented in 93 cases. Survival was significantly influenced by lymph node status (p = 0.0001), number of involved nodes (p = 0.0001), number of dissected nodes in pN0 patients (p = 0.0001) and application of adjuvant systemic therapy in pN0 patients (p = 0.0001).

CONCLUSIONS: The pathological examination of axillary nodes in breast cancer patients offers a valuable information regarding survival. The absence of lymph node metastases of 10 lymph nodes dissection or more, and the application of adjuvant systemic therapy favorably influence the survival.}, } @article {pmid22043354, year = {2010}, author = {Arafah, M and Kfoury, HK and Zaidi, SN}, title = {HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors.}, journal = {Oman medical journal}, volume = {25}, number = {4}, pages = {261-263}, pmid = {22043354}, issn = {2070-5204}, abstract = {OBJECTIVES: HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 (3+) by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis.

METHODS: A retrospective analysis of 18 cases (3+) by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error (i.e staining of blood vessels or benign ducts) and the interpretation errors were evaluated.

RESULTS: Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors.

CONCLUSION: False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast.}, } @article {pmid22042364, year = {2012}, author = {Kim, J and Lee, S and Bae, S and Choi, MY and Lee, J and Jung, SP and Kim, S and Choe, JH and Kim, JH and Kim, JS and Lee, JE and Nam, SJ and Yang, JH}, title = {Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes.}, journal = {Breast cancer research and treatment}, volume = {131}, number = {2}, pages = {527-540}, doi = {10.1007/s10549-011-1836-0}, pmid = {22042364}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*classification/*diagnosis/mortality ; Carcinoma, Ductal, Breast/*classification/*diagnosis/mortality ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Breast cancer screening programs make it possible to detect early cancer, thus reducing breast cancer mortality. We studied the clinicopathologic characteristics and prognosis of screen-detected invasive breast cancer compared with symptomatic breast cancer. And we compared the result according to molecular subtypes (luminal A, luminal B, Her2, and triple negative), with the goal of identifying the role of screening in each subtypes. From January 2002 to June 2008, 3,141 patients who underwent surgery for the treatment of invasive ductal carcinoma at Samsung Medical Center were included. Among them, 1,025 patients were screen-detected, and 2,116 patients who were screened over 2 years or never were symptomatic. We retrospectively reviewed the clinical and pathologic data. Screen-detected breast cancer was associated with older age, smaller tumor size, more hormone-receptor positive, less lymph node involvement, earlier stage, and reduced mortality compared with symptomatic breast cancer (P < 0.001). According to the molecular subtype, luminal A was most common (63.6%) and showed the most obvious survival benefit in screen-detected tumors in comparison with symptomatic tumors (5-year OS: 99.7 vs. 96.5%, 5-year DFS: 96.4 vs. 90.7%). Screen detection was independently associated with improved overall and disease-free survival outcomes after adjustment for covariates (HR 0.32, P = 0.035; HR 0.58, P = 0.020, respectively) only in the luminal A subtype. Differences in pathological features such as tumor size, nodal status, grade, and age at diagnosis with different molecular subtype distributions may explain the survival advantage of patients with screen-detected breast cancer. Screening programs seem to have a different efficacy depending on the molecular subtype of the breast cancer, especially in the luminal A subtype, for which screen detection acts as an independent prognostic factor itself.}, } @article {pmid22039080, year = {2012}, author = {Colleoni, M and Rotmensz, N and Maisonneuve, P and Mastropasqua, MG and Luini, A and Veronesi, P and Intra, M and Montagna, E and Cancello, G and Cardillo, A and Mazza, M and Perri, G and Iorfida, M and Pruneri, G and Goldhirsch, A and Viale, G}, title = {Outcome of special types of luminal breast cancer.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {23}, number = {6}, pages = {1428-1436}, doi = {10.1093/annonc/mdr461}, pmid = {22039080}, issn = {1569-8041}, mesh = {Adenocarcinoma/mortality/*pathology/therapy ; Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/mortality/*pathology/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; *Neoplasm Recurrence, Local ; Neoplasms, Hormone-Dependent/mortality/*pathology/therapy ; Proportional Hazards Models ; }, abstract = {BACKGROUND: The identification of special types of breast cancer might be of value in assessing prognosis and predicting response to therapy.

METHODS: A total of 7372 consecutive patients with immunohistochemically defined luminal invasive breast cancer operated at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence by histological type. Median follow-up was 5.8 years.

RESULTS: Tumors from 5707 patients were classified as invasive ductal cancer (IDC) not otherwise specified (NOS), 851 lobular, 338 mixed ductal and lobular, 250 cribriform, 143 mucinous and 83 tubular carcinomas. Compared with IDC NOS disease-free survival (DFS) was significantly longer in patients with cribriform tumors [5-year DFS 97.9% versus 87.4%; hazard ratio (HR) = 0.48; P = 0.015) and in pooled cribriform plus tubular carcinomas (5-year DFS 98.7% versus 87.4%; HR = 0.45; P = 0.005). Mucinous tumors presented similar DFS if compared with IDC (5-year DFS 93 % versus 87.4%; HR = 1.03; P = 0.91). Conversely, DFS was poorer for patients with lobular carcinoma (5-year DFS 86.8% versus 87.4%; HR = 1.27; P = 0.01).

CONCLUSIONS: The diagnosis of tubular, cribriform and lobular carcinomas carry distinct prognostic implications. The identification of these special types has a significant utility in luminal breast cancer and should be considered in therapeutic algorithms.}, } @article {pmid22037080, year = {2011}, author = {Ugiagbe, EE and Olu-Eddo, AN and Obaseki, DE}, title = {Immunohistochemical detection of Her-2/neu overexpression in breast carcinoma in Nigerians: a 5-year retrospective study.}, journal = {Nigerian journal of clinical practice}, volume = {14}, number = {3}, pages = {332-337}, doi = {10.4103/1119-3077.86779}, pmid = {22037080}, issn = {1119-3077}, mesh = {Adenocarcinoma/*diagnosis/metabolism ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Female ; Hospitals, Teaching ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Nigeria ; Prognosis ; Rabbits ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: To determine the pattern of Her-2/neu status among breast carcinoma in the University of Benin Teaching Hospital, Benin City, Nigeria.

MATERIALS AND METHODS: Immunohistochemical staining for Her-2/neu was performed on 10% formalin-fixed, paraffin-embedded primary carcinoma of the breast from 83 patients, between 2003 and 2007 using anti-Her-2/neu rabbit polyclonal antibody (DakoCytomation, CA, USA) and reactivity detected by an avidin-biotin immunoperoxidase method. The clinicopathologic parameters analyzed were patients' age, histological types, and tumor grade. The Her-2/neu Dako scoring system was used.

RESULTS: During the 5-year period, 83 histologically confirmed cases of invasive breast carcinoma were assessed for Her-2/neu status. These included 67 (80.7%) cases of invasive ductal carcinoma, nine cases of invasive lobular carcinoma (10.8%), three cases of medullary carcinoma (3.6%), two cases of papillary carcinoma (2.4%), and a case each of mucinous and clear cell carcinoma (1.2%). Mean age of patients was 48.9 ± 13.6 years with an age range of 25 to 83 years. Only nine (10.8%) cases showed immunopositivity for Her-2/neu. Seven of these were cases of invasive ductal carcinoma, while two were invasive lobular carcinoma. Tumors were predominantly high grade with grade III, II, and I accounting for 42, 28, and 13 cases, respectively. There was no significant correlation between patient age, the various histological types, tumor grade, and Her-2/neu positivity.

CONCLUSIONS: This study indicates that Her-2/neu may not be useful in defining the prognosis of breast cancer in this environment. Nevertheless, it highlights the need for routine immunostaining for Her-2/neu before institution of trastuzumab (Herceptin) therapy.}, } @article {pmid22031807, year = {2011}, author = {Quinlan-Davidson, S and Hodgson, N and Elavathil, L and Shangguo, T}, title = {Borderline phyllodes tumor with an incidental invasive tubular carcinoma and lobular carcinoma in situ component: a case report.}, journal = {Journal of breast cancer}, volume = {14}, number = {3}, pages = {237-240}, pmid = {22031807}, issn = {2092-9900}, abstract = {Phyllodes tumors are an infrequent breast tumor presentation. A phyllodes tumor with a synchronous invasive ductal carcinoma is rarely described and has never been reported with lobular carcinoma in situ component. A 53-year-old female presented with a nine-year history of twice core biopsy proven fibroadenoma. After an increase in the tumor's growth velocity it was decided upon to undergo an excisional biopsy. Microscopic examination of the well-circumscribed pale-tan mass found focal areas of leaf like architecture with variable number of mitoses present, representing a phyllodes tumor of borderline malignant potential. Incidentally, at one edge of the mass was found a tubular carcinoma and lobular carcinoma in situ components. Thorough, routine follow-up of patients with biopsy proven benign breast masses is important to finding a masked malignant component.}, } @article {pmid22030565, year = {2011}, author = {Barbosa, AP and Cardinalli Neto, A and Otaviano, AP and Rocha, BF and Bestetti, RB}, title = {Comparison of outcome between Chagas cardiomyopathy and idiopathic dilated cardiomyopathy.}, journal = {Arquivos brasileiros de cardiologia}, volume = {97}, number = {6}, pages = {517-525}, doi = {10.1590/s0066-782x2011005000112}, pmid = {22030565}, issn = {1678-4170}, mesh = {Adrenergic beta-Antagonists/adverse effects/therapeutic use ; Cardiomyopathy, Dilated/diagnostic imaging/drug therapy/*mortality ; Chagas Cardiomyopathy/diagnostic imaging/drug therapy/*mortality ; Digoxin/adverse effects/therapeutic use ; Epidemiologic Methods ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Ultrasonography ; }, abstract = {BACKGROUND: Little is known about the outcome of patients with Chagas cardiomyopathy in comparison to that of patients with idiopathic dilated cardiomyopathy in the contemporary era.

OBJECTIVE: To compare the outcome of chagasic patients with chronic systolic heart failure secondary to Chagas cardiomyopathy with that observed in patients with IDC in the contemporary era.

METHODS: A total of 352 patients (246 with Chagas cardiomyopathy, 106 with idiopathic dilated cardiomyopathy) prospectively followed at our Institution from January, 2000 to January, 2008 were included. All patients received standard contemporary medical therapy.

RESULTS: In Cox proportional hazards model multivariate analysis, digoxin use (Hazard Ratio=3.17; 95% Confidence Interval 1.62 to 6.18; p=0.001), need of inotropic support (Hazard Ratio=2.08; 95% Confidence Interval 1.43 to 3.02; p<0.005), left ventricular ejection fraction (Hazard Ratio=0.97; 95% Confidence Interval 0.95 to 0.99; p<0.005), and Chagas cardiomyopathy etiology (Hazard Ratio=3.29; 95% Confidence Interval 1.89 to 5.73; p<0.005) were positively associated with mortality, whereas beta-blocker therapy (Hazard Ratio=0.39; 95% Confidence Interval 0.26 to 0.56; p<0.005) was negatively associated with mortality. Survival probability for patients with Chagas cardiomyopathy at 8, 24, and 49 months was 83%, 61%, and 41%, respectively, and for patients with idiopathic dilated cardiomyopathy 97%, 92%, and 82%, respectively (p<0.005).

CONCLUSION: In the current era of heart failure therapy, patients with Chagas cardiomyopathy have a poorer outcome in comparison to patients with idiopathic dilated cardiomyopathy.}, } @article {pmid22030137, year = {2011}, author = {Sullu, Y and Demirag, GG and Yildirim, A and Karagoz, F and Kandemir, B}, title = {Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.}, journal = {Pathology, research and practice}, volume = {207}, number = {12}, pages = {747-753}, doi = {10.1016/j.prp.2011.09.010}, pmid = {22030137}, issn = {1618-0631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast/metabolism/pathology ; Breast Neoplasms/enzymology/mortality/*pathology ; Carcinoma, Ductal, Breast/enzymology/mortality/*pathology ; Female ; Gelatinases/metabolism ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Matrix Metalloproteinase 2/*metabolism ; Matrix Metalloproteinase 9/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Young Adult ; }, abstract = {Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.}, } @article {pmid22026308, year = {2011}, author = {Araki, K and Shimura, T and Kobayashi, T and Saito, K and Wada, W and Sasaki, S and Suzuki, H and Kashiwabara, K and Nakajima, T and Kuwano, H}, title = {Mixed ductal-endocrine carcinoma of the pancreas occurring as a double cancer: report of a case.}, journal = {International surgery}, volume = {96}, number = {2}, pages = {153-158}, doi = {10.9738/cc8.1}, pmid = {22026308}, issn = {0020-8868}, mesh = {Aged ; Carcinoma, Neuroendocrine/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Carcinoma, Renal Cell/*pathology/surgery ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Kidney Neoplasms/*pathology/surgery ; Lymph Nodes/surgery ; Male ; Neoplasms, Multiple Primary/*pathology ; Nephrectomy ; Pancreatic Neoplasms/metabolism/*pathology/surgery ; Pancreaticoduodenectomy ; Prognosis ; }, abstract = {We present a successfully treated case of mixed ductal-endocrine carcinoma of the pancreas complicated by right renal cell carcinoma. The patient had no symptoms, and laboratory data were close to the normal range. Enhanced computed tomography demonstrated a marked enhanced tumor, which appeared to be an endocrine tumor, at the pancreas uncus. We performed pyrolus-preserving pancreaticoduodenectomy, regional lymph node resection, and right nephrectomy. Histologically and immunohistochemically, the pancreas tumor had both a ductal (exocrine) and an endocrine component. The renal tumor was a typical clear cell carcinoma. A diagnosis of synchronous double cancer was made. As demonstrated in previously published reports, this type of mixed tumor has malignant potential for invasive ductal carcinoma. We propose that mixed ductal-endocrine carcinoma of the pancreas should be treated by surgical resection with a sufficient surgical margin and regional lymph node resection to improve the patient's prognosis.}, } @article {pmid22025283, year = {2012}, author = {Duprez, R and Wilkerson, PM and Lacroix-Triki, M and Lambros, MB and MacKay, A and A'Hern, R and Gauthier, A and Pawar, V and Colombo, PE and Daley, F and Natrajan, R and Ward, E and MacGrogan, G and Arbion, F and Michenet, P and Weigelt, B and Vincent-Salomon, A and Reis-Filho, JS}, title = {Immunophenotypic and genomic characterization of papillary carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {226}, number = {3}, pages = {427-441}, pmid = {22025283}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; CTR-Q3REIS-FILHO/BCN_/Breast Cancer Now/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Papillary/*genetics/pathology ; Case-Control Studies ; Class I Phosphatidylinositol 3-Kinases ; Female ; Humans ; Immunophenotyping/methods ; Lymphatic Metastasis ; Mutation/genetics ; Phenotype ; Phosphatidylinositol 3-Kinases/genetics ; Receptors, Estrogen/genetics ; }, abstract = {Papillary carcinomas are a special histological type of breast cancer and have a relatively good outcome. We characterized the genomic and phenotypic characteristics of papillary carcinomas to determine whether they would constitute an entity distinct from grade- and oestrogen receptor (ER)-matched invasive ductal carcinomas of no special type (IDC-NSTs). The phenotype of 63 papillary carcinomas of the breast and grade- and ER-matched IDC-NSTs was determined by immunohistochemistry. DNA of sufficient quality was extracted from 49 microdissected papillary carcinomas and 49 microdissected grade- and ER-matched IDC-NSTs. These samples were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY sequencing analysis of 19 known oncogenes. Papillary carcinomas were predominantly of low histological grade, expressed immunohistochemical markers consistent with a luminal phenotype, and a lower rate of lymph node metastasis and p53 expression than grade- and ER-matched IDC-NSTs. Papillary carcinomas displayed less genomic aberrations than grade- and ER-matched IDC-NSTs; however, the patterns of gene copy number aberrations found in papillary carcinomas were similar to those of ER- and grade-matched IDC-NSTs, including 16q losses. Furthermore, PIK3CA mutations were found in 43% and 29% of papillary carcinomas and grade- and ER-matched IDC-NSTs, respectively. The genomic profiles of encapsulated, solid and invasive papillary carcinomas, the three morphological subtypes, were remarkably similar. Our results demonstrate that papillary carcinomas are a homogeneous special histological type of breast cancer. The similarities in the genomic profiles of papillary carcinomas and grade- and ER-matched IDC-NSTs suggest that papillary carcinomas may be best positioned as part of the spectrum of ER-positive breast cancers, rather than as a distinct entity. Furthermore, the good prognosis of papillary carcinomas may stem from the low rates of lymph node metastasis and p53 expression, low number of gene copy number aberrations and high prevalence of PIK3CA mutations.}, } @article {pmid22020211, year = {2011}, author = {Ghosn, M and Hajj, C and Kattan, J and Farhat, F and El Karak, F and Nasr, F and Abadjian, G and Chahine, G}, title = {Triple-negative breast cancer in Lebanon: a case series.}, journal = {The oncologist}, volume = {16}, number = {11}, pages = {1552-1556}, pmid = {22020211}, issn = {1549-490X}, mesh = {Adult ; Breast Neoplasms/*epidemiology/*metabolism/mortality/therapy ; Disease-Free Survival ; Female ; Humans ; Incidence ; Lebanon/epidemiology ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; Young Adult ; }, abstract = {OBJECTIVES: To determine the incidence, characteristics, and survival outcomes of triple-negative breast cancer patients in a medical oncology practice in Lebanon.

METHODS: The pathology reports of all breast cancer cases diagnosed or treated in 1997-2008 were reviewed.

RESULTS: One hundred seventy breast cancer cases (9.3%) of the 1,834 cases that were identified in this practice over a 10-year span had a triple-negative phenotype, with a median age at diagnosis of 52 years. The pathology distribution of those cases was as follows: invasive ductal carcinoma, 85%; medullary carcinoma, 5%; invasive lobular carcinoma, 5%; 95 cases (63%) were grade III. At diagnosis, 17% presented with stage I, 47% had stage II, 24% had stage III, and 12% had stage IV disease, whereas 11% had an inflammatory component. After a median follow-up of 17 months, 43 patients (25.3%) had relapsed and the most common sites of relapse were the brain (19%), lungs (19%), and bones (12%). The risk for recurrence peaked at 1.5 years and became almost nil after 3 years. Twenty patients received induction chemotherapy, among whom six (42.9%) had a complete response and six (42.9%) had a partial response to treatment. None of the patients progressed on neoadjuvant chemotherapy. The 5-year disease-free survival rate was 75% for stage I, 58% for stage II, and 40% for stage III patients, whereas the 5-year overall survival rate was 88% for stage I, 72% for stage II, and 63% for stage III patients. Adjuvant therapy was administered to 96% of patients, using a taxane-based regimen in 38% of cases. The median survival time for stage IV patients was 19 months, with a first line taxane-based regimen used in 50% of cases.

CONCLUSIONS: The incidence of triple-negative breast cancer in Lebanon is similar to that described in the literature. In order to determine targets for future therapeutic options, it is essential to understand the biology of this particular breast cancer subtype.}, } @article {pmid22017615, year = {2011}, author = {Halperin, E and Gross, JJ}, title = {Emotion regulation in violent conflict: reappraisal, hope, and support for humanitarian aid to the opponent in wartime.}, journal = {Cognition & emotion}, volume = {25}, number = {7}, pages = {1228-1236}, doi = {10.1080/02699931.2010.536081}, pmid = {22017615}, issn = {1464-0600}, mesh = {*Altruism ; Arabs ; *Cognition ; Data Collection/methods/statistics & numerical data ; *Emotions ; Female ; Humans ; Israel ; Jews/*psychology ; Male ; Violence/*psychology ; *Warfare ; }, abstract = {It is well known that negative intergroup emotions such as anger, fear, and hatred play a major role in initiating and maintaining intergroup conflicts. It is far less clear, however, what factors promote the resolution of intergroup conflicts. Using an emotion regulation- framework, we hypothesised that one form of emotion regulation-namely cognitive reappraisal-should play a salutary role in such conflicts, and be associated with increased hope as well as greater support for humanitarian aid to out-group members. To test these hypotheses, we used a nationwide survey of Jewish-Israeli adults, conducted during the war in Gaza between Israelis and Palestinians. Results obtained via structural equation modelling revealed that Israelis who regulated their negative emotions during the war through reappraisal were more supportive in providing humanitarian aid to innocent Palestinian citizens and that this relation was partially mediated by an enhanced feeling of hope.}, } @article {pmid22015727, year = {2012}, author = {Wetterskog, D and Lopez-Garcia, MA and Lambros, MB and A'Hern, R and Geyer, FC and Milanezi, F and Cabral, MC and Natrajan, R and Gauthier, A and Shiu, KK and Orr, N and Shousha, S and Gatalica, Z and Mackay, A and Palacios, J and Reis-Filho, JS and Weigelt, B}, title = {Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers.}, journal = {The Journal of pathology}, volume = {226}, number = {1}, pages = {84-96}, doi = {10.1002/path.2974}, pmid = {22015727}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Adenoid Cystic/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Female ; Gene Dosage ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Microdissection ; Oncogene Proteins, Fusion/*genetics ; Receptor, ErbB-3/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; }, abstract = {Adenoid cystic carcinoma (AdCC) is a rare form of triple-negative and basal-like breast cancer that has an indolent clinical behaviour. Four breast AdCCs were recently shown to harbour the recurrent chromosomal translocation t(6;9)(q22-23;p23-24), which leads to the formation of the MYB-NFIB fusion gene. Our aims were (i) to determine the prevalence of the MYB-NFIB fusion gene in AdCCs of the breast; (ii) to characterize the gene copy number aberrations found in AdCCs; and (iii) to determine whether AdCCs are genomically distinct from histological grade-matched or triple-negative and basal-like invasive ductal carcinomas of no special type (IDC-NSTs). The presence of the MYB-NFIB fusion gene was investigated in 13 AdCCs of the breast by fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR), and MYB and BRCA1 RNA expression was determined by quantitative RT-PCR. Fourteen AdCCs, 14 histological grade-matched IDC-NSTs, and 14 IDC-NSTs of triple-negative and basal-like phenotype were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). The MYB-NFIB fusion gene was detected in all but one AdCC. aCGH analysis demonstrated a relatively low number of copy number aberrations and a lack of recurrent amplifications in breast AdCCs. Contrary to grade-matched IDC-NSTs, AdCCs lacked 1q gains and 16q losses, and in contrast with basal-like IDC-NSTs, AdCCs displayed fewer gene copy number aberrations and expressed MYB and BRCA1 at significantly higher levels. Breast AdCCs constitute an entity distinct from grade-matched and triple-negative and basal-like IDC-NSTs, emphasizing the importance of histological subtyping of triple-negative and basal-like breast carcinomas.}, } @article {pmid22014044, year = {2011}, author = {Wang, S and Li, W and Lv, S and Wang, Y and Liu, Z and Zhang, J and Liu, T and Niu, Y}, title = {Abnormal expression of Nek2 and β-catenin in breast carcinoma: clinicopathological correlations.}, journal = {Histopathology}, volume = {59}, number = {4}, pages = {631-642}, doi = {10.1111/j.1365-2559.2011.03941.x}, pmid = {22014044}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; NIMA-Related Kinases ; Neoplasm Grading ; Neoplasm Staging ; Protein Serine-Threonine Kinases/*biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; beta Catenin/*biosynthesis ; }, abstract = {AIMS: NIMA-related kinase 2 (Nek2) and β-catenin are important centrosome regulatory factors. The aim of this study was to detect the possible disparity in their expression among normal breast tissue, invasive ductal carcinoma (IDC), concomitant ductal carcinoma in situ (DCIS), and pure DCIS, and to explore its correlation with clinicopathological factors.

METHODS AND RESULTS: We used immunohistochemistry to detect protein expression of Nek2 and β-catenin in breast cancer tissues from 60 cases of pure DCIS, 348 cases of IDC and 137 cases of concomitant DCIS with that in normal breast tissues from the same 137 concomitant DCIS patients as controls. As compared with normal tissue, expression of Nek2 and β-catenin in the cytoplasm was significantly increased in IDC and DCIS (P < 0.05), and variation in expression was also observed in different grades of IDC (P < 0.01). Also, cytoplasmic expression of Nek2 and and of β-catenin were correlated with each other in IDC and DCIS (P < 0.01). In addition, they were both related to Ki67 immunoreactivity (P < 0.05). Furthermore, our study also revealed a correlation between their expression and some clinicopathological factors. We found that Nek2 cytoplasmic expression was associated with grade and tumour size (P < 0.01) in IDC, whereas β-catenin cytomembrane expression showed significant variation with grades, TNM stages, lymphoid node status, oestrogen receptor status, and molecular subtype (P < 0.05); a difference in expression was also observed between IDC and DCIS (P < 0.05). Also, β-catenin cytoplasmic expression was associated with TNM stage (P < 0.05). Expression of Nek2 at the mRNA level was detected in 50 pairs of breast cancer specimens and matched normal tissues by reverse transcriptase polymerase chain reaction, and the result showed increased expression in IDC.

CONCLUSIONS: This study suggests that abnormal expression of Nek2 and β-catenin might be one of the mechanisms of tumorigenesis, especially of abnormal tumour proliferation. They may represent new potential targets for therapeutic intervention.}, } @article {pmid22012049, year = {2011}, author = {ElMoneim, HM and Zaghloul, NM}, title = {Expression of E-cadherin, N-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {66}, number = {10}, pages = {1765-1771}, pmid = {22012049}, issn = {1980-5322}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Chi-Square Distribution ; Disease Progression ; Egypt ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptors, Steroid/metabolism ; Snail Family Transcription Factors ; Statistics, Nonparametric ; Transcription Factors/*metabolism ; }, abstract = {OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features.

METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas.

RESULTS: The expression of E-cadherin was decreased (negative or weak) in 37.1% of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9% and 40.9% of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1%), positive node status (80.9%), poor Nottingham Prognostic Index (64.7%), and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8%) and nuclear Snail (69.4%).

CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.}, } @article {pmid22011761, year = {2012}, author = {Wu, T and Li, Y and Gong, L and Lu, JG and Du, XL and Zhang, WD and He, XL and Wang, JQ}, title = {Multi-step process of human breast carcinogenesis: a role for BRCA1, BECN1, CCND1, PTEN and UVRAG.}, journal = {Molecular medicine reports}, volume = {5}, number = {2}, pages = {305-312}, doi = {10.3892/mmr.2011.634}, pmid = {22011761}, issn = {1791-3004}, mesh = {Adult ; Aged ; Apoptosis Regulatory Proteins/genetics/*metabolism ; BRCA1 Protein/genetics/*metabolism ; Beclin-1 ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cyclin D1/genetics/*metabolism ; Female ; G1 Phase ; Humans ; Membrane Proteins/genetics/*metabolism ; Middle Aged ; PTEN Phosphohydrolase/genetics/*metabolism ; RNA, Messenger/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; }, abstract = {In the female population in Asia, systematic investigation concerning alterations in cancer-related genes in breast carcinoma is rare, and the correlation among oncogene or suppressor gene expression with tumor cell apoptosis, cell cycle regulation and tumor cell autophagy remains to be clarified. In this study, a tissue microarray consisting of 360 individual samples from three different breast tissues was generated. By comparing the expression of the tumor-suppressor genes (BRCA1, BECN1, CCND1, PTEN and UVRAG) in ductal breast cancer and normal breast tissues, respectively, we were able to assign changes in the expression of these mRNAs to specific stages and allocate them to define the roles in the multi‑step process of breast carcinogenesis. Tumor-suppressor genes, such as BRCA1 and BECN1, usually had lower signals in the carcinomatous tissues (10.2 and 6.6%) compared to the normal tissues (31 and 32.6%), while stronger positive dots (positive cells >30%) usually existed in the normal tissues. The patients in the oldest age group had the lowest expression rate. Only BECN1 and CCND1 expression showed a significant association with patient age (p=0.030 and p=0.003). A significant association was observed between BRCA1 and BECN1 expression and tumor size (p=0.028 and p=0.021). BECN1 gene expression was positively correlated with UVRAG and PTEN expression (p=0.006 and p=0.000). CCND1 was negatively correlated with PTEN, BECN1 and BRCA1 expression (p=0.011, p=0.000 and p=0.000). Abnormal expression of BRCA1, BECN1, CCND1, PTEN and UVRAG may play a role in human breast carcinogenesis through dysregulated mRNA expression. Overexpressed CCND1 may shorten the G1 phase of the cell cycle, suppress cell apoptosis and contribute to the formation of invasive ductal carcinoma (IDC).}, } @article {pmid22011102, year = {2011}, author = {Guttmann-Steinmetz, S and Crowell, J and Doron, G and Mikulincer, M}, title = {Associations between mothers' and children's secure base scripts in ADHD and community cohorts.}, journal = {Attachment & human development}, volume = {13}, number = {6}, pages = {597-610}, doi = {10.1080/14616734.2011.609010}, pmid = {22011102}, issn = {1469-2988}, mesh = {Adolescent ; Attention Deficit Disorder with Hyperactivity/physiopathology/*psychology ; Child ; Cohort Studies ; Female ; Humans ; Male ; *Mother-Child Relations ; Surveys and Questionnaires ; United States ; }, abstract = {This study explored the relation between mothers' and their children's secure base scripts in two samples of school-aged children: a community sample (N = 29; mean age 8.9) and a sample of children diagnosed with ADHD (N = 50; mean age 8.9). Using the Attachment Script Representation Task, mothers and children were asked to construct narratives using word prompt outlines. In addition, mothers and children completed questionnaires focusing on symptoms. The results revealed that while the link between mothers' and children's scriptedness was significant in the community, no significant association was found in the ADHD sample. In the ADHD group, maternal reports of children's symptoms were negatively linked to children's secure-base scriptedness. Implications of these findings for theory and intervention are discussed.}, } @article {pmid22011099, year = {2011}, author = {Zilcha-Mano, S and Mikulincer, M and Shaver, PR}, title = {Pet in the therapy room: an attachment perspective on Animal-Assisted Therapy.}, journal = {Attachment & human development}, volume = {13}, number = {6}, pages = {541-561}, doi = {10.1080/14616734.2011.608987}, pmid = {22011099}, issn = {1469-2988}, mesh = {Adaptation, Psychological ; *Animal Assisted Therapy ; Animals ; *Human-Animal Bond ; Humans ; *Object Attachment ; Psychological Theory ; }, abstract = {John Bowlby's (1973, 1980, 1982) attachment theory is one of the most influential theories in personality and developmental psychology and provides insights into adjustment and psychopathology across the lifespan. The theory is also helpful in defining the target of change in psychotherapy, understanding the processes by which change occurs, and conceptualizing cases and planning treatment (Daniel, 2006; Obegi & Berant, 2008; Sable, 2004 ; Wallin, 2007). Here, we propose a model of Animal-Assisted Therapy (AAT) based on attachment theory and on the unique characteristics of human-pet relationships. The model includes clients' unmet attachment needs, individual differences in attachment insecurity, coping, and responsiveness to therapy. It also suggests ways to foster the development of more adaptive patterns of attachment and healthier modes of relating to others.}, } @article {pmid22006548, year = {2012}, author = {Sun, S and Jiang, Y and Zhang, G and Song, H and Zhang, X and Zhang, Y and Liang, X and Sun, Q and Pang, D}, title = {Increased expression of fibroblastic growth factor receptor 2 is correlated with poor prognosis in patients with breast cancer.}, journal = {Journal of surgical oncology}, volume = {105}, number = {8}, pages = {773-779}, doi = {10.1002/jso.22120}, pmid = {22006548}, issn = {1096-9098}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/*pathology ; Cytoplasm/metabolism ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 2/*metabolism ; Survival Rate ; }, abstract = {BACKGROUND AND OBJECTIVES: Although there is growing evidence supporting the hypothesis that fibroblast growth factor receptor 2 (FGFR2) is one of the few candidate genes linked with breast cancer susceptibility, the precise role of FGFR2 protein expression in breast cancer is still unknown. Our study examines FGFR2 protein expression in breast cancer and determines its associations with clinicopathological features and survival.

METHODS: Specimens from 125 invasive ductal carcinoma grade 2 (IDC2) breast cancer patients were investigated by immunohistochemistry for FGFR2 protein expression. Associations between the expression of FGFR2 and various clinicopathological features as well as survival status were studied.

RESULT: Cytoplasmic and nuclear FGFR2 were expressed in 64.8% and 56.8% of breast cancer patients, respectively. Cytoplasmic FGFR2 expression was significantly associated with tumor size and TNM stage. Furthermore, patients with high expression levels of cytoplasmic and nuclear FGFR2 showed much lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low FGFR2 expression. Cytoplasmic FGFR2 expression and lymph node metastasis were independent prognostic factors for both DFS and OS by multivariate analysis.

CONCLUSIONS: High FGFR2 expression is correlated with poor OS and DFS in breast cancer patients. It could be a biomarker for poor prognosis.}, } @article {pmid22000861, year = {2012}, author = {Jardim, BV and Moschetta, MG and Gelaleti, GB and Leonel, C and Regiani, VR and de Santi Neto, D and Bordin-Junior, NA and Perea, SA and Zuccari, DA}, title = {Glutathione transferase pi (GSTpi) expression in breast cancer: an immunohistochemical and molecular study.}, journal = {Acta histochemica}, volume = {114}, number = {5}, pages = {510-517}, doi = {10.1016/j.acthis.2011.09.005}, pmid = {22000861}, issn = {1618-0372}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Glutathione S-Transferase pi/*genetics ; Humans ; Immunohistochemistry ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; }, abstract = {Breast cancer is the most frequent cancer in women worldwide. Prognostic markers are important for diagnosis, allowing therapeutic strategies to be defined more efficiently. The expression of the glutathione S-transferase pi isoenzyme (GSTpi) in tumor cells has been evaluated as a predictor of prognosis and in response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results were statistically correlated with clinicopathological parameters of patients. The results showed that high GSTpi expression was related to p53-positive tumors, grade III histology, large tumor size and death (p<0.05). The 37 patients who received adjuvant treatment, checked separately, showed high expression of GSTpi in relation to local recurrence, metastasis and death (p<0.05). In addition, high levels of GSTpi expression were significantly associated with a shorter overall survival (p<0.05). To confirm this suspicion, GSTpi gene expression was checked by Real-time PCR in neoplastic mammary cells cultured and subjected to treatment with doxorubicin. Our results suggest that high levels of GSTpi may be related to the development of resistance to chemotherapy in these tumors, the response of these tumors to treatment and the clinical course of the patients involved.}, } @article {pmid21989447, year = {2011}, author = {Lang, R and Fan, Y and Fu, X and Fu, L}, title = {Metaplastic breast carcinoma with extensive osseous differentiation: a report of two cases and review of the literature.}, journal = {Tumori}, volume = {97}, number = {4}, pages = {e1-5}, doi = {10.1177/030089161109700421}, pmid = {21989447}, issn = {2038-2529}, mesh = {Adenocarcinoma/chemistry/*pathology ; Axilla ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Calcinosis/*diagnosis ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Mastectomy, Modified Radical ; Mastectomy, Segmental ; Metaplasia ; Middle Aged ; Necrosis/diagnosis ; Ossification, Heterotopic/*diagnosis ; Osteosarcoma/diagnosis ; Treatment Outcome ; }, abstract = {Invasive breast cancer with osseous metaplasia is rare. Here we report two cases of metaplastic breast carcinoma with extensive osseous differentiation. Case 1: The patient was a 60-year-old woman with a right breast tumor, about 4 cm in diameter. Mammogram and ultrasound presented an irregular-shaped mass suspected for malignancy. Core needle biopsy confirmed invasive carcinoma and the patient underwent a modified radical mastectomy. Case 2: The patient was a 48-year-old woman with a left breast tumor, about 3 cm in diameter. Mammogram demonstrated a well-circumscribed mass with extensive dense calcifications. Frozen section biopsy confirmed invasive carcinoma and a modified radical mastectomy was performed. The two patients had no metastatic carcinoma in the axillary lymph nodes and remained free of recurrence and systemic metastases in a 13- and 4-month follow-up period, respectively. Histopathologically, patient 1 had an adenocarcinoma with prominent sarcomatous (osteosarcomatous) differentiation with intervening spindle cells. The sarcomatous areas showed high nuclear atypia, pleomorphism and a high Ki-67 index. In Case 2, the neoplasm consisted of invasive ductal carcinoma of no special type with an osseous metaplasia component and showed a direct transition from the carcinoma to the osseous elements. The distinction between the different types of metaplastic carcinomas, specifically the distinction between benign and malignant metaplastic (osteoid) elements, should be taken into consideration.}, } @article {pmid21989445, year = {2011}, author = {Jelisavac-Cosic, S and Sirotkovic-Skerlev, M and Kulic, A and Jakic-Razumovic, J and Kovac, Z and Vrbanec, D}, title = {Prognostic significance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) in patients with primary invasive ductal breast carcinoma - a 7.5-year follow-up study.}, journal = {Tumori}, volume = {97}, number = {4}, pages = {532-539}, doi = {10.1177/030089161109700419}, pmid = {21989445}, issn = {2038-2529}, mesh = {Adult ; Aged ; Analysis of Variance ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/mortality ; Carcinoma, Ductal, Breast/*chemistry/mortality ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Plasminogen Activator Inhibitor 1/*analysis ; Predictive Value of Tests ; Prognosis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Urokinase-Type Plasminogen Activator/*analysis ; }, abstract = {AIMS AND BACKGROUND: Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) are key molecules in pericellular proteolysis, a process that plays an important role in tumor invasion and metastasis. In the current study we investigated the prognostic significance of uPA and PAI-1 in primary invasive breast cancer.

METHODS AND STUDY DESIGN: uPA and PAI-1 antigen levels were determined by enzyme-linked immunosorbent assay in cytosols of 177 invasive ductal carcinoma specimens. The prognostic significance of uPA and PAI-1 was assessed for overall survival. The median follow-up time was 90 months.

RESULTS: In univariate analysis, both uPA (third versus first tertile range of values; P = 0.02; HR = 2.08) and PAI-1 (third versus first tertile; P = 0.0007; HR = 3.1) were significant prognostic markers for overall survival. In multivariate analysis only nodal status (N2 vs N0; P = 0.0001; HR = 3.94) and PAI-1 (third versus first tertile; P = 0.004; HR = 3.05) remained significant independent prognostic factors. Both uPA and PAI-1 were correlated with established prognostic markers including histological grade, tumor size and Nottingham index.

CONCLUSION: Our study with a 7.5-year follow-up confirmed the relation between elevated uPA and PAI-1 values and an aggressive course of invasive breast cancer. The prognostic significance of PAI-1 as an independent marker was proved for the overall group of breast cancer patients and the subgroup of node-positive patients.}, } @article {pmid21987945, year = {2011}, author = {Dauda, AM and Misauno, MA and Ojo, EO}, title = {Histopathological types of breast cancer in Gombe, North Eastern Nigeria: a seven-year review.}, journal = {African journal of reproductive health}, volume = {15}, number = {1}, pages = {109-111}, pmid = {21987945}, issn = {1118-4841}, mesh = {Adult ; Age Factors ; Aged ; Breast/*pathology ; *Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Histocytological Preparation Techniques ; Humans ; Male ; Middle Aged ; Nigeria/epidemiology ; Pathology Department, Hospital/statistics & numerical data ; *Registries ; Retrospective Studies ; Sex Factors ; }, abstract = {This was a retrospective analysis of all consecutive breast cancer specimens submitted to the Pathology Department Of Federal Medical Centre, Gombe which renders histopathology services to four states in the North Eastern region of Nigeria. A total of 172 cases of malignant breast tumours were recorded during the 7 years under review. Out of the 172 cases of breast cancers analysed, 7 (4%) were in males while the remaining 165 (96%) were in females giving a male: female ratio of 1:24. The most common histopathological type of breast cancer found in this study was Invasive Ductal Carcinoma no special type (NST) accounting for 78.8% of cases.}, } @article {pmid21987494, year = {2013}, author = {Akashi, S and Kuwabara, H and Kurisu, Y and Takahashi, Y and Yasuda, E and Takeshita, A and Ishizaki, S and Tsuji, M and Shibayama, Y}, title = {Fine-needle aspiration cytology of triple-negative basal-like breast cancer.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {4}, pages = {283-287}, doi = {10.1002/dc.21807}, pmid = {21987494}, issn = {1097-0339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Biopsy, Fine-Needle/*methods ; Carcinoma, Medullary/diagnosis ; Cell Nucleus/pathology ; Cell Nucleus Shape ; Chromatin/pathology ; Female ; Humans ; Middle Aged ; Mitotic Index ; Neoplasm Grading ; Neoplasm Metastasis/diagnosis ; Receptor, ErbB-2/genetics/metabolism ; Sensitivity and Specificity ; Triple Negative Breast Neoplasms/*diagnosis ; }, abstract = {Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC.}, } @article {pmid21987420, year = {2013}, author = {Dey, P and Logasundaram, R and Joshi, K}, title = {Artificial neural network in diagnosis of lobular carcinoma of breast in fine-needle aspiration cytology.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {2}, pages = {102-106}, doi = {10.1002/dc.21773}, pmid = {21987420}, issn = {1097-0339}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Fibroadenoma/*pathology ; Humans ; *Neural Networks, Computer ; *Software ; }, abstract = {In this study, we applied artificial neural network (ANN) for the diagnosis of lobular carcinoma in fine-needle aspiration cytology (FNAC) material. We selected a total of 64 cases of histology proven breast lesions consisting of 20 fibroadenomas, 28 infiltrating ductal carcinomas (IDC), and 16 infiltrating lobular carcinomas (ILC). Detailed cytomorphological features were studied on representative Haematoxylin-Eosin (H&E) and May-Grunwald Giemsa stained slides. Image morphometric analysis was performed on Haematoxylin-Eosin stained smears to study nuclear area, diameter, perimeter, roundness, convex area, and convex perimeter. Both the qualitative cytological features and objective morphometric data were collected and a total of 18 variables were studied. Back propagation ANN was designed and this data were used as input values. ANN network was designed as 34-17-3. There were a total of 34 first layers neurons, 17 hidden neurons and three output neurons. The total cases were randomly divided automatically by the program into three groups: training set (40), validation set (8), and test set (16). After the successful training, the program was able to differentiate all the benign and lobular carcinoma cases and majority of the ductal carcinoma cases. In test set, the ANN program successfully classified all the cases of benign, and ILC cases and six of seven IDC cases. A suitably designed ANN may be able to diagnose the lobular carcinoma of breast on FNAC material. ANN is an efficient software program with immense potential.}, } @article {pmid21987354, year = {2013}, author = {Goel, S and Bhatia, A and Dey, P}, title = {Spontaneously occurring micronuclei in infiltrating ductal carcinoma of breast: a potential biomarker for aggressive phenotype detection?.}, journal = {Diagnostic cytopathology}, volume = {41}, number = {4}, pages = {296-302}, doi = {10.1002/dc.21836}, pmid = {21987354}, issn = {1097-0339}, mesh = {Adolescent ; Adult ; Aged ; Aneuploidy ; Biomarkers, Tumor/*analysis ; Biopsy, Fine-Needle ; Breast/*pathology ; Carcinoma, Ductal/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Cell Nucleus/*pathology ; Cell Nucleus Shape ; Cell Nucleus Size ; Chromosomal Instability ; Epithelial Cells/pathology ; Female ; Humans ; India ; Middle Aged ; Neoplasm Grading ; Phenotype ; Tertiary Care Centers ; Young Adult ; }, abstract = {Chromosomal instabilities (CIN) manifesting as structural or numerical alterations in the chromosomes are common in malignancies like breast cancer. Assessment of CIN in breast cancer may help to understand its etiopathogenesis. Micronucleus (MN) scoring and aneuploidy have been used to assess the presence of CIN in lymphocytes of various malignancies in the past. In this study, spontaneously occurring MN were counted in epithelial cells on fine needle aspiration cytology (FNAC) smears from 50 patients with benign and malignant breast lesions. Further, the ploidy status and S-phase fraction (SPF) of the samples was determined by flow cytometry. All these were then correlated with grades of breast cancer at cytology. Most IDC cases showed variable number of MN (n = 16, MN mean = 9.3), in contrast to the benign lesions (n = 26) where they were consistently absent. Aneuploidy and SPF analysis also showed a significant difference between benign (n = 10, mean DNA index [DI] = 0.96 ± 0.04, mean SPF= 8.07% ± 2.93) and malignant (n = 10, mean DI = 1.5 ± 0.41, mean SPF = 25.05% ± 10.35) lesions. On statistical analysis, a positive correlation was observed between the grades of IDC and presence of aneuploidy and high SPF (P-values < 0.05); however, the difference between the MN scores of grade 2 and 3 cancers was not significant. The study suggests that MN scoring and aneuploidy may be used to assess the presence of underlying CIN in IDC on FNAC smears. Further, collectively they may be explored for their role as biomarkers for predicting the tumor behavior in the breast cancer patients.}, } @article {pmid21987236, year = {2012}, author = {Naushad, SM and Prayaga, A and Digumarti, RR and Gottumukkala, SR and Kutala, VK}, title = {Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast.}, journal = {Molecular and cellular biochemistry}, volume = {361}, number = {1-2}, pages = {189-195}, pmid = {21987236}, issn = {1573-4919}, mesh = {8-Hydroxy-2'-Deoxyguanosine ; Amplified Fragment Length Polymorphism Analysis ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; DNA Methylation ; Deoxyguanosine/analogs & derivatives/metabolism ; *Epigenesis, Genetic ; Female ; Ferredoxin-NADP Reductase/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Glycine Hydroxymethyltransferase/*genetics/metabolism ; Humans ; Membrane Proteins/*genetics/metabolism ; Oxidative Stress ; Phenotype ; Polymorphism, Genetic ; Prognosis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/*genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2'deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR-RFLP and PCR-AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08, P < 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (P = 0.034) and methionine synthase reductase (MTRR) A66G (P = 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (P < 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml, P < 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (P < 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.}, } @article {pmid21983893, year = {2012}, author = {Endo, H and Saito, T and Kenjo, A and Hoshino, M and Terashima, M and Sato, T and Anazawa, T and Kimura, T and Tsuchiya, T and Irisawa, A and Ohira, H and Hikichi, T and Takagi, T and Gotoh, M}, title = {Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {19}, number = {4}, pages = {465-475}, doi = {10.1007/s00534-011-0457-7}, pmid = {21983893}, issn = {1868-6982}, mesh = {Adenocarcinoma/*immunology/pathology/surgery/*therapy ; Aged ; Antineoplastic Agents/*administration & dosage ; Combined Modality Therapy ; Dendritic Cells/*immunology ; *Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Feasibility Studies ; Female ; Humans ; Immunohistochemistry ; Injections, Intralesional ; Lymph Nodes/pathology ; Lymphocytes, Tumor-Infiltrating ; Male ; Middle Aged ; Pancreatic Neoplasms/*immunology/pathology/surgery/*therapy ; Picibanil/*administration & dosage ; Preoperative Period ; }, abstract = {PURPOSE: To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients.

METHODS: Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien-Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+).

RESULTS: There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy.

CONCLUSION: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.}, } @article {pmid21983862, year = {2012}, author = {Wong, H and Lau, S and Leung, R and Chiu, J and Cheung, P and Wong, TT and Liang, R and Epstein, RJ and Yau, T}, title = {Coexisting ductal carcinoma in situ independently predicts lower tumor aggressiveness in node-positive luminal breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {3}, pages = {1536-1542}, pmid = {21983862}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasms, Multiple Primary/*pathology ; Retrospective Studies ; }, abstract = {Primary breast invasive ductal carcinoma coexisting with ductal carcinoma in situ (IDC-DCIS) is characterized by lower proliferation rate and metastatic propensity than size-matched pure IDC. IDC-DCIS is also more often ER-positive, PR-positive and/or HER2-positive. This analysis aims to clarify whether the presence of coexisting DCIS in IDC affects tumor aggressiveness in various biological subtypes of breast cancer, respectively. Tumor data obtained from 1,355 consecutive female patients undergoing upfront surgery for primary breast cancer were analyzed retrospectively; 196 patients with pure DCIS were excluded. Based on evidence that immunohistochemistry (IHC) provides a reasonable approximation of molecular phenotypes, the tumor samples were divided into 4 groups: (1) luminal A (ER and/or PR-positive, HER2-negative, Ki67 ≤ 12), (2) luminal B (ER and/or PR-positive, HER2-negative, Ki67 > 12), (3) HER2 (HER2-positive) and (4) basal-like (triple-negative) disease. Ki67 expression and nodal involvement of IDC with or without DCIS in these groups were compared. The number of patients with luminal A, luminal B, HER2 and basal-like breast cancer were 396, 265, 258 and 117, respectively. Ki-67 was lower in IDC-DCIS than in size-adjusted pure IDC of both luminal A and luminal B subtypes (P = 0.15 and <0.005, respectively). In HER2 or basal-like tumors, there were no significant difference between pure IDC and IDC-DCIS. The presence of coexisting DCIS in IDC predicts lower biological aggressiveness in luminal cancers but not in the conventionally more aggressive HER2-positive and triple-negative subtypes.}, } @article {pmid21981134, year = {2012}, author = {Tamaki, K and Ishida, T and Miyashita, M and Amari, M and Mori, N and Ohuchi, N and Tamaki, N and Sasano, H}, title = {Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients.}, journal = {Cancer science}, volume = {103}, number = {1}, pages = {67-72}, doi = {10.1111/j.1349-7006.2011.02116.x}, pmid = {21981134}, issn = {1349-7006}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/mortality/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/mortality/*pathology ; Female ; Humans ; Middle Aged ; *Multidetector Computed Tomography ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53 years (26-89 years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2- (P = 0.008), while the well-demarcated type was higher in ER-/HER2- and ER-/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER-/HER2- (P < 0.001). Intermediate or low density was higher in ER-/HER2- (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well-demarcated shape was higher in grade 2 and 3 (P = 0.006 and P < 0.001, respectively), and rim pattern was observed in grade 3 (P < 0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P = 0.008 and P = 0.014), while well-demarcated shape and rim enhancement were observed in score 3 (P < 0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P = 0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P = 0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients.}, } @article {pmid21980445, year = {2011}, author = {van Damme, P and Kafeja, F and Anemona, A and Basile, V and Hilbert, AK and De Coster, I and Rondini, S and Micoli, F and Qasim Khan, RM and Marchetti, E and Di Cioccio, V and Saul, A and Martin, LB and Podda, A}, title = {Safety, immunogenicity and dose ranging of a new Vi-CRM197 conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.}, journal = {PloS one}, volume = {6}, number = {9}, pages = {e25398}, pmid = {21980445}, issn = {1932-6203}, mesh = {Adult ; Bacterial Proteins/*adverse effects/*immunology ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Female ; Health ; Humans ; Male ; Polysaccharides, Bacterial/*adverse effects/*immunology ; Typhoid Fever/immunology/*prevention & control ; Typhoid-Paratyphoid Vaccines/*adverse effects/*immunology ; Vaccines, Conjugate/adverse effects/immunology ; Young Adult ; }, abstract = {BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults.

METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine.

PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.

CONCLUSIONS: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.}, } @article {pmid21977324, year = {2012}, author = {Liesmaa, I and Shiota, N and Kokkonen, JO and Kovanen, PT and Lindstedt, KA}, title = {Bradykinin type-2 receptor expression correlates with age and is subjected to transcriptional regulation.}, journal = {International journal of vascular medicine}, volume = {2012}, number = {}, pages = {159646}, pmid = {21977324}, issn = {2090-2832}, abstract = {Accumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end-stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated cardiomyopathy (IDC; n = 7), coronary heart disease (CHD; n = 6), and normal patients (n = 6) were analyzed by RT-PCR, SSCP, and Western blotting. In normal and IDC hearts, BK-2R expression increased with age, with a lower relative increase in IDC hearts. BK-2R mRNA and protein levels showed a positive linear correlation, suggesting transcriptional regulation. Two known BK-2R promoter polymorphisms, -58T/C and -9/+9, were found to be present in the study population. The allelic frequencies for the C-allele in -58T/C were 0.58 in normal and CHD hearts and 0.81 in IDC hearts. Furthermore, the allelic frequencies for the -9 and +9 alleles were 0.42 and 0.58 in normal hearts and 0.64 and 0.36 in IDC hearts, respectively. All analyzed CHD hearts were homozygous for the -9 allele. Thus, the expression of cardioprotective BK-2Rs in human hearts is increased with age in normal and IDC hearts and may be regulated on the transcriptional level. Moreover, comparison of normal subjects and patients with failing hearts revealed different allelic frequencies in each of two known BK-2R gene polymorphisms.}, } @article {pmid21975420, year = {2011}, author = {Cottier, O and Fiche, M and Meuwly, JY and Delaloye, JF}, title = {Dermatofibrosarcoma presenting as a nodule in the breast of a 75-year-old woman: a case report.}, journal = {Journal of medical case reports}, volume = {5}, number = {}, pages = {503}, pmid = {21975420}, issn = {1752-1947}, abstract = {INTRODUCTION: Dermatofibrosarcoma protuberans is a rare neoplasm of soft tissues and its location in the breast is extremely uncommon. Confusion is possible with other primary breast lesions.

CASE PRESENTATION: A 75-year-old Caucasian woman presented with a mass in her left breast 21 years after being diagnosed with invasive ductal carcinoma of the right breast, treated by a right mastectomy and axillary dissection followed by radiotherapy and breast reconstruction. Mammography revealed a dish-shaped skin nodule formation in the upper outer quadrant of her left breast. Echography confirmed the presence of a lesion measuring 1.4 × 0.8 cm. Based on imaging, the diagnosis was a probable angiosarcoma. Due to the presence of a pacemaker for cardiac arrhythmia and full anticoagulation therapy for a pulmonary embolism, magnetic resonance imaging and a biopsy were not done. We proceeded directly to a quadrantectomy and the final diagnosis revealed a dermatofibrosarcoma protuberans, 1. 8 cm in its greatest microscopic dimension, located 0.1 cm from the upper surgical margin. To ensure the wide resection margins required for this type of neoplasm, a re-excision was performed.

CONCLUSION: A dermatofibrosarcoma protuberans of the breast is an uncommon discovery. The aim of this case report is to highlight the importance of the surgical procedure in cases of the discovery of dermatofibrosarcoma protuberans. Re-excision may be necessary to ensure adequate resection margins.}, } @article {pmid21971852, year = {2011}, author = {Nunes, RD and Martins, E and Freitas-Junior, R and Curado, MP and Freitas, NM and Oliveira, JC}, title = {Descriptive study of breast cancer cases in Goiânia between 1989 and 2003.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {38}, number = {4}, pages = {212-216}, doi = {10.1590/s0100-69912011000400002}, pmid = {21971852}, issn = {1809-4546}, mesh = {Adult ; Brazil/epidemiology ; Breast Neoplasms/*epidemiology/pathology ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Time Factors ; }, abstract = {OBJECTIVE: To describe cases of breast cancer in women living in Goiânia from 1989-2003.

METHODS: We conducted a retrospective, descriptive stud, which included all cases of breast cancer occurring in residents of Goiânia, identified by the Population-Based Cancer Registry of Goiânia (RCBPGO) in the period from 1989 to 2003. The variables were: age, method of diagnosis, topographic location, morphology and extent of breast cancer. We used frequencies and percentage rates, and Poisson regression to determine the annual percentage change (APC).

RESULTS: We identified 3204 cases of breast cancer. The most frequent topographic location was the superior-lateral quadrant (53.7%). Infiltrating ductal carcinoma (IDC) was the most frequent, with 2582 cases (80.6%), followed by infiltrating lobular carcinoma (ILC), with 155 cases (4.8%). There was a significant increase of both the IDC and the ILC, with APCs of 11.0% and 15.4%, respectively. The ratio between IDC and ILC was not influenced by age (p = 0.98). As for tumor extent at diagnosis, 45.6% were located in the breast, and the APC was 16.1% (CI = 12.4 to 20.0, p <0.001). There was a trend of APC reduction of metastatic cases (-3.8, CI = -8.6 to 1.2, p = 0.12).

CONCLUSION: The topographical location and histological type of breast cancer in the city of Goiania followed the pattern of other countries. The main morphological types were not influenced by age. There was a large increase in initial cases.}, } @article {pmid21969708, year = {2011}, author = {Huang, YT and Cheung, YC and Lo, YF and Ueng, SH and Kuo, WL and Chen, SC}, title = {MRI findings of cancers preoperatively diagnosed as pure DCIS at core needle biopsy.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {52}, number = {10}, pages = {1064-1068}, doi = {10.1258/ar.2011.110213}, pmid = {21969708}, issn = {1600-0455}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Predictive Value of Tests ; *Preoperative Period ; ROC Curve ; Retrospective Studies ; }, abstract = {BACKGROUND: Under-estimation of invasion components occur occasionally at core needle diagnosed ductal carcinoma in situ (DCIS) that may change the prognosis or treatment planning.

PURPOSE: To determine whether enhanced magnetic resonance imaging (MRI) features of biopsy-proven ductal cancers in situ help predict the under-estimation of invasive breast cancers.

MATERIAL AND METHODS: After a retrospective review of the enhanced MRI features on preoperative proven breast ductal cancers in situ by biopsy, tumor morphology (mass and non-mass), enhancing curve patterns, and non-mass enhanced appearances were compared between pure ductal cancers in situ and invasive ductal cancers (IDCs) after surgery. A statistical analysis was performed, and P values <0.05 were deemed significant.

RESULTS: Twenty-five breast cancers from 24 women were analyzed. Eleven DCIS remained as DCISs, and 14 were upgraded to IDC after surgery. Eight of 14 IDCs (57%) and one of 11 DCISs (9%) presented as mass lesions; otherwise six (43%) IDCs and 10 (91%) DCISs were non-mass lesions (P = 0.013). Among the non-mass cancers, six of 10 DCISs (60%) were focally enhanced and six of 6 IDCs (100%) were segmentally enhanced. The overall cancer sizes measured on enhanced MRI were moderately correlated with histopathology, with a Spearman's rank correlation coefficient of 0.656 (P = 0.001). The mean diameter of the IDCs was larger than that of the pure DCISs on enhanced MRI (2.69 ± 1.42 cm for IDC and 1.62 ± 1.03 cm for DCIS; P = 0.048). The cut-off size was optimally selected at 1.95 cm with a 64% sensitivity and a 77% specificity, using a receiver-operating characteristic curve. The enhancement curves, with washout or persistent rising, were statistically insignificant (P = 0.085 and 0.93, respectively).

CONCLUSION: Enhanced MRI provided informative morphology and size features that might help to predict the underestimation of invasiveness in preoperative biopsy-proven DCIS.}, } @article {pmid21969162, year = {2011}, author = {Izumi, H and Okada, K and Imaizumi, T and Hirabayashi, K and Matsuyama, M and Dowaki, S and Tobita, K and Makuuchi, H}, title = {Leiomyosarcoma of the pancreas: report of a case.}, journal = {Surgery today}, volume = {41}, number = {11}, pages = {1556-1561}, pmid = {21969162}, issn = {1436-2813}, mesh = {Adult ; Biopsy, Needle ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; *Incidental Findings ; Leiomyosarcoma/*diagnosis/surgery ; Magnetic Resonance Imaging/methods ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/*diagnosis/surgery ; Rare Diseases ; Risk Assessment ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in the literature. We encountered a rare case of leiomyosarcoma of the pancreas, treated successfully by surgery. A 41-year-old woman was referred to our hospital for further examinations of a pancreatic tumor. Imaging studies demonstrated a solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This mass had a nonuniform content and was encapsulated. We performed distal pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal carcinoma. Macroscopically, a sagittal section of the operative specimen showed a well-circumscribed yellowish-white mass without any cystic changes. Immunohistological examination revealed that α-smooth muscle actin, desmin, and vimentin were positive, and the labeling index of MIB-1 was 50% or more. Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating from the pancreas. During 14 months of follow-up to date, there has not been any evidence of local recurrence or distant metastasis.}, } @article {pmid21966777, year = {2011}, author = {Carabias-Meseguer, P and Cusidó-Gimferrer, M and Zapardiel-Gutiérrez, I and Tresserra-Casas, F and Fábregas-Xauradó, R and Xercavins-Montoya, J}, title = {[Node status in 454 ductal breast cancers cases according to the association with in situ component].}, journal = {Ginecologia y obstetricia de Mexico}, volume = {79}, number = {1}, pages = {5-10}, pmid = {21966777}, issn = {0300-9041}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology/*secondary ; Carcinoma, Intraductal, Noninfiltrating/classification/epidemiology/*pathology ; Disease Progression ; Female ; Humans ; Hyperplasia/pathology ; *Lymphatic Metastasis ; Mexico/epidemiology ; Middle Aged ; Necrosis ; Neoplasm Invasiveness/pathology ; Precancerous Conditions/epidemiology/pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Studies have shown that breast infiltrating ductal carcinoma develops from precursor lesions or pre-invasive. It is accepted that the risk of invasive ductal carcinoma increased slightly in hyperplasia, but especially in cases of atypical hyperplasia and intraductal carcinoma.

OBJECTIVES: To evaluate and compare the nodal status between ductal breast cancer with in situ component (group 1) or without it (group 2).

MATERIAL AND METHOD: Descriptive and retrospective study that included 454 ductal breast cancers. Data concerning clinical and pathological variables was collected. All data was compared between both groups.

RESULTS: Among all cases, 176 (38.8%) showed positive lymph nodes, 136 patients (39.5%) from group 1 and 40 cases (36.4%) from group 2. Among group 1 cases, high-grade subgroup showed higher positive lymph node rate (82 cases, 55.4%) than the extensive in situ carcinomas subgroup (84 cases, 49.7%). Both of them had a significant higher rate than group 2 cases (p = 0.003 y p = 0.028, respectively). Moreover, the low-grade in situ carcinomas without cellular necrosi had positive lymph nodes just in 30 cases (24%), significantly lower (p = 0.034) than group 2.

CONCLUSIONS: We did not find overall statistical differences between groups depending on in situ associated component. But when we analyzed in situ subgroups, we found differences with higher positive lymph node rate in high grade carcinomas and extensive in situ carcinomas subgroups, while lower affectation rates were observed in low grade carcinomas (without cellular necrosis), compared to the group of breast cancers without in situ component associated.}, } @article {pmid21965772, year = {2011}, author = {Yamamoto, D and Tsubota, Y and Yoshida, H and Kanematsu, S and Sueoka, N and Uemura, Y and Tanaka, K and Kwon, AH}, title = {Endoscopic appearance and clinicopathological character of breast cancer.}, journal = {Anticancer research}, volume = {31}, number = {10}, pages = {3517-3520}, pmid = {21965772}, issn = {1791-7530}, mesh = {Breast Neoplasms/*pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease-Free Survival ; *Endoscopy ; Female ; Humans ; }, abstract = {BACKGROUND: The Japanese Association of Mammary Ductoscopy proposed a classification system based on the objective endoscopic appearance of intraductal lesions. This system includes four categories: solitary polypoid, multiple polypoid, superficial, and combined type. However, previous studies did not adequately compare endoscopic findings with histological findings and the prognosis.

PATIENTS AND METHODS: One hundred and ten patients with nipple discharge who had intraductal tumors were identified by mammary ductoscopy, and 25 breast cancer patients were identified from our database of records between 2001 and 2008. The clinicopathological data and outcomes of these patients were then reviewed.

RESULTS: Lesions in 25 breast cancer patients comprised 12 polypoid solitary type, 3 polypoid multiple type, 5 superficial type, and 5 combined type. Polypoid type showed a low sensitivity on cytological analysis (5 malignant and 10 benign). On the contrary, superficial or combined type showed a high sensitivity (4 malignant and 1 benign). Furthermore, invasive ductal carcinoma was frequently found in the solitary polypoid type. Actuarial disease-free survival for all patients at 10 years was 78%. The estrogen/progesterone receptor status and endoscopic appearance did not significantly affect disease-free survival (DFS), while there was a significant difference in DFS between ductal carcinoma in situ and invasive ductal carcinoma.

CONCLUSION: Ductoscopy is a useful procedure for guiding subsequent breast surgery in the treatment of nipple discharge, and the appearance may be essential in treating breast cancer patients with nipple discharge.}, } @article {pmid21962285, year = {2011}, author = {Lemberger, SI and Deeg, CA and Hauck, SM and Amann, B and Hirmer, S and Hartmann, K and Dorsch, R}, title = {Comparison of urine protein profiles in cats without urinary tract disease and cats with idiopathic cystitis, bacterial urinary tract infection, or urolithiasis.}, journal = {American journal of veterinary research}, volume = {72}, number = {10}, pages = {1407-1415}, doi = {10.2460/ajvr.72.10.1407}, pmid = {21962285}, issn = {1943-5681}, mesh = {Animals ; Biomarkers/*urine ; Blotting, Western/veterinary ; Cat Diseases/*urine ; Cats ; Cystitis/diagnosis/urine/*veterinary ; Electrophoresis/veterinary ; Fibronectins/analysis ; Immunohistochemistry/veterinary ; Proteinuria/*veterinary ; Urinary Bladder/pathology ; Urinary Tract Infections/urine/*veterinary ; Urolithiasis/urine/*veterinary ; }, abstract = {OBJECTIVE: To characterize and compare the urine protein content in cats without urinary tract disease and cats with idiopathic cystitis (IdC), bacterial urinary tract infection (UTI), or urolithiasis.

ANIMALS: Control cats (n = 18) and cats with IdC (18), UTI (12), and urolithiasis (12) from which urine samples were obtained and 2 cats with obstructive IdC and 4 additional control cats from which postmortem urinary bladder biopsy specimens were obtained.

PROCEDURES: Protein contents in urine samples obtained via cystocentesis or catheterization were measured via the Bradford method. Urine proteins were separated by means of 1-dimensional gel electrophoresis. Evaluation of fibronectin content was performed via western blotting and immunohistochemical analysis. Urinary bladder biopsy specimens were examined histologically and analyzed immunohistochemically for fibronectin.

RESULTS: Urine fibronectin content was significantly greater in cats with IdC, compared with control cat findings. Urine fibronectin contents did not differ significantly among controls and cats with UTI or urolithiasis. Histologic examination of bladder biopsy specimens obtained from 2 cats with obstructive IdC revealed destruction of the urothelial lining of the urinary bladder and severe fibrosis; immunohistochemical analysis revealed few fluorescence signals for fibronectin, unlike findings in control bladder biopsy specimens.

Results indicated that urine fibronectin content in cats with IdC was greater than that in controls, cats with UTI, or cats with urolithiasis. In cats with IdC, increased permeability of damaged urothelium may result in detachment and leakage of fibronectin into urine. Urine fibronectin might serve as a biomarker for diagnosis of IdC in cats.}, } @article {pmid23472437, year = {2011}, author = {Khan, MI and ul Haque, A and Younas, M and Zafar, A and Shah, H}, title = {Metaplastic squamous cell carcinoma in association with invasive lobular breast carcinoma with metastasis to axillary lymph nodes.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {23}, number = {4}, pages = {135-137}, pmid = {23472437}, issn = {1025-9589}, mesh = {Adult ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Carcinoma, Squamous Cell/*pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Neoplasm Invasiveness ; }, abstract = {Squamous cell carcinoma (SCC) of the breast is very rare entity and when encountered it is found in association with invasive ductal carcinoma of the breast. We report a very unusual association of an invasive lobular carcinoma with metaplastic squamous cell carcinoma of the breast which was found not only in a mastectomy specimen but also in the axillary lymph nodes. The patient reported first with a lump breast which was diagnosed a case of invasive lobular carcinoma in a lumpectomy specimen, followed by adjunct radiation and chemotherapy. We encountered such association in only one case report in the literature.}, } @article {pmid21956537, year = {2012}, author = {Bernardi, MA and Logullo, AF and Pasini, FS and Nonogaki, S and Blumke, C and Soares, FA and Brentani, MM}, title = {Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer.}, journal = {Oncology reports}, volume = {27}, number = {1}, pages = {28-38}, doi = {10.3892/or.2011.1477}, pmid = {21956537}, issn = {1791-2431}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; CD24 Antigen/analysis/*biosynthesis ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Claudins/analysis/*biosynthesis ; Female ; Humans ; Hyaluronan Receptors/analysis/biosynthesis ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis/biosynthesis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism/pathology ; Prognosis ; Tissue Array Analysis ; }, abstract = {This study aimed to identify the CD24 and CD44 immunophenotypes within invasive ductal breast carcinoma (IDC) subgroups defined by immunohistochesmistry markers and to determine its influence on prognosis as well as its association with the expression of Ki-67, cytokeratins (CK5 and CK18) and claudin-7. Immunohistochemical expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). The association with subgroups defined as luminal A and B; HER2 rich and triple negative, or with the other markers and prognosis was analyzed. CD44+/CD24- and CD44-/CD24+ were respectively present in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD44+/CD24+ was observed in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44+/CD24- phenotype was more common in the basal subgroups but absent in HER2 tumors, whereas luminal tumors are enriched in CD44-/CD24+ and CD44+/CD24+ cells. The frequency of CD44+/CD24- or CD44-/CD24+ was not associated with clinical characteristics or biological markers. There was also no significant association of these phenotypes with the event free (DFS) and overall survival (OS). Single CD44+ was evident in 57.9% of the tumors and was marginally associated to grading and not to any other tumor characteristics as well as OS and DFS. CD24+ was positive in 74.7% of the tumors, showing a significant association with estrogen receptor, progesterone receptor and Ki-67 and a marginal association with CK18 and claudin-7. Expression of claudin-7 and Ki-67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found (P=0.03). CK5, CK18 and Ki-67 expression had no influence in OS or DFS. Single CD24+ (P=0.07) and claudin-7 positivity (P=0.05) were associated with reduced time of recurrence, suggesting a contribution of these markers to aggressiveness of breast cancer.}, } @article {pmid21954546, year = {2011}, author = {Fidan, E and Yildiz, B and Ersoz, S and Ozdemir, F}, title = {Bilateral breast cancer: a male patient.}, journal = {Bratislavske lekarske listy}, volume = {112}, number = {10}, pages = {589-590}, pmid = {21954546}, issn = {0006-9248}, mesh = {Breast Neoplasms, Male/diagnosis/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*pathology/therapy ; Humans ; Male ; Middle Aged ; }, abstract = {Bilateral breast cancer represents less than 2% of male patients with breast cancer. A 63-year old male presented with a mass at right breast and modified radical mastectomy was performed. Pathology was reported as invasive ductal carcinoma. Radiotherapy and tamoxifen was administered following chemotherapy. At the 5th month, a mass was detected at left breast and modified radical mastectomy was performed. Chemotherapy was started postoperatively. BRCA1 and BRCA2 were reported negative. Although male breast cancer is rare, male patients with breast cancer may have cancer at the other breast (Fig. 1, Ref. 5).}, } @article {pmid21948695, year = {2012}, author = {Karan, B and Pourbagher, A and Bolat, FA}, title = {Unusual malignant breast lesions: imaging-pathological correlations.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {18}, number = {3}, pages = {270-276}, doi = {10.4261/1305-3825.DIR.4454-11.2}, pmid = {21948695}, issn = {1305-3612}, mesh = {Breast Neoplasms/diagnostic imaging/*pathology ; Female ; Humans ; Middle Aged ; Radiography ; Ultrasonography ; }, abstract = {This pictorial essay presents the common radiological (mammography and/or ultrasonography) and pathological findings observed in unusual malignant breast lesions, which include well-differentiated subtypes of invasive ductal carcinoma not otherwise specified (tubular, mucinous, papillary, and medullary carcinomas), metaplastic carcinoma, and metastases. This study also includes unusual ultrasonographic appearances of a plasmacytoma.}, } @article {pmid21943448, year = {2011}, author = {Critchley, AC and Harvey, J and Carr, M and Iwuchukwu, O}, title = {Synchronous gastric and colonic metastases of invasive lobular breast carcinoma: case report and review of the literature.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {93}, number = {5}, pages = {e49-50}, pmid = {21943448}, issn = {1478-7083}, mesh = {*Breast Neoplasms ; Carcinoma, Lobular/*secondary ; Colonic Neoplasms/*secondary ; Female ; Humans ; Middle Aged ; Stomach Neoplasms/*secondary ; }, abstract = {Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma. The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum. The presentation of GI metastasis due to breast cancer is typically vague and the clinical, radiological, endoscopic and histopathologic findings are often difficult to distinguish from primary gastric carcinoma. Such a patient is more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon. Therefore a high index of clinical suspicion with early endoscopy in those with non-specific symptoms and a past history of breast cancer, particularly ILC, are recommended. It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Therefore, correlation of endoscopic biopsy histology with the primary breast cancer histology is essential. Treatment modalities are limited to appropriate systemic therapy, which may have a palliative effect in up to 50%. Surgical intervention is nearly always limited to palliative bypass only. Prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer.}, } @article {pmid21943250, year = {2011}, author = {Xiang, L and Su, P and Xia, S and Liu, Z and Wang, Y and Gao, P and Zhou, G}, title = {ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {90}, pmid = {21943250}, issn = {1746-1596}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/*biosynthesis ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*pathology ; Neoplasm Proteins/*biosynthesis ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/biosynthesis ; Tissue Array Analysis ; }, abstract = {BACKGROUND: ABCG2 is an ABC transporter. It has been demonstrated that endogenous ABCG2 expression in certain cancers is a possible reflection of the differentiated phenotype of the cell of origin and likely contributes to intrinsic drug resistance. But little is known about the contribution of ABCG2 to the drug resistance and the clinicopathological characteristics in breast cancer. In the present study, we investigated the expression of ABCG2 and the correlations between ABCG2 expression and patients' clinicopathological and biological characteristics.

METHODS: Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 breast cancer patients with clinicopathological data.

RESULTS: The results showed that ABCG2 was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive stain for ABCG2 was defined as a brown stain observed in the cytoplasm and cytomembrane. A statistically significant correlation was demonstrated between ABCG2 expression and HER-2 expression (p = 0.001), lymph node metastasis (p = 0.049), and clinical stage (p = 0.015) respectively.

CONCLUSION: ABCG2 correlated with Her-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. It could be a novel potential bio-marker which can predict biological behavior, clinical progression, prognosis and chemotherapy effectiveness.}, } @article {pmid21935747, year = {2012}, author = {King, TA and Sakr, RA and Muhsen, S and Andrade, VP and Giri, D and Van Zee, KJ and Morrow, M}, title = {Is there a low-grade precursor pathway in breast cancer?.}, journal = {Annals of surgical oncology}, volume = {19}, number = {4}, pages = {1115-1121}, doi = {10.1245/s10434-011-2053-0}, pmid = {21935747}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma in Situ/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/therapy ; Carcinoma, Lobular/metabolism/*pathology/therapy ; Disease Progression ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/pathology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: Newly proposed models of breast tumorigenesis suggest that low- and high-grade lesions have distinct tumor progression pathways. Our objective was to examine the relationship between histologic grade and molecular subtype in women with lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) who developed subsequent ipsilateral invasive breast cancers.

METHODS: Patients who underwent surveillance for classical LCIS (1994-2007) and those followed after lumpectomy±radiation for DCIS (1991-2004) who developed subsequent ipsilateral invasive cancers and had available tissue blocks were included. ER/PR/HER2 surrogates were used for molecular subtype.

RESULTS: Material was available for 27 patients with classical LCIS who developed ipsilateral invasive cancer (12 invasive ductal cancer [IDC], 14 invasive lobular, 1 mixed), and 26 patients with DCIS (12 low-grade [LG], 14 high-grade [HG]) who developed ipsilateral IDC. No difference in age at diagnosis or median time to invasive cancer existed between groups with LCIS and DCIS. When stratified by grade, 0 of 12 LG-DCIS developed LG-IDC (3 grade II; 9 grade III), and only 1 of 12 LCIS patients who developed IDC had LG-IDC. Thirteen (93%) patients with HG-DCIS developed HG-IDC. In contrast, molecular subtype was maintained in 23 of 27 (85%) cases of LCIS and in 18 of 26 (69%) cases of DCIS.

CONCLUSIONS: These data do not support a low-grade precursor pathway characterized by LCIS and LG-DCIS. ER/PR and HER2 status have a high rate of concordance between in situ and subsequent invasive lesions. Additional studies of metachronous in situ and invasive lesions are needed to better understand pathways of breast tumorigenesis.}, } @article {pmid21935605, year = {2011}, author = {Akbulut, S and Sogutcu, N and Yagmur, Y}, title = {Coexistence of breast cancer and tuberculosis in axillary lymph nodes: a case report and literature review.}, journal = {Breast cancer research and treatment}, volume = {130}, number = {3}, pages = {1037-1042}, doi = {10.1007/s10549-011-1634-8}, pmid = {21935605}, issn = {1573-7217}, mesh = {Aged ; Axilla ; Carcinoma, Ductal, Breast/*complications/*pathology ; Female ; Granuloma/pathology ; Humans ; Lymph Nodes/*pathology ; Tuberculosis, Lymph Node/*complications/*pathology ; }, abstract = {Coexistence of breast cancer and tuberculosis (TB) of the breast and/or axillary lymph nodes is uncommon. In this article, we present a case of tuberculous axillary lymphadenitis existing simultaneously with invasive ductal carcinoma of the left breast. We also conducted an extensive literature review of English language studies published on the coexistence of breast cancer and TB of the breast and/or axillary lymph nodes from 1899 to 2011 using the PubMed and Google Scholar databases. Twenty-nine cases of coexisting breast cancer and TB of the breast and/or axillary lymph nodes have been published to date, including a 74-year-old female diagnosed with left breast cancer and TB of the axillary lymph nodes. A tumor in the right breast was detected in 14 patients and in the left breast in 12 patients between the ages of 28 and 81 years, but no data were available regarding the side on which the tumor occurred in three patients. Eighteen patients underwent a modified radical mastectomy, five patients underwent a radical mastectomy, two a lumpectomy and an axillary lymph node dissection (ANLD), two a quadrantectomy (Q) and an ALND, and two an applied excision. TB was detected at the axilla in all 21 patients in patients with no TB of the breast, and TB was also detected in the axilla in five of eight patients with breast TB. Both a tumor and TB lymphadenitis were detected following an axillary dissection in 14 patients, and both cancer metastasis and TB lymphadenitis were detected at the same lymph nodes in six of these patients. The simultaneous occurrence of these two major illnesses in the breast and/or axillary lymph nodes can produce many problems with respect to diagnosis and treatment. Accurate diagnoses are necessary for down-staging carcinoma of the breast and for identifying curable disease.}, } @article {pmid21934215, year = {2011}, author = {Murthy, SS and Sandhya, DG and Ahmed, F and Goud, KI and Dayal, M and Suseela, K and Rajappa, SJ}, title = {Assessment of HER2/Neu status by fluorescence in situ hybridization in immunohistochemistry-equivocal cases of invasive ductal carcinoma and aberrant signal patterns: a study at a tertiary cancer center.}, journal = {Indian journal of pathology & microbiology}, volume = {54}, number = {3}, pages = {532-538}, doi = {10.4103/0377-4929.85087}, pmid = {21934215}, issn = {0974-5130}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal/*diagnosis/pathology ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence/*methods ; India ; Mastectomy ; Microscopy ; Middle Aged ; Pathology, Molecular/*methods ; Receptor, ErbB-2/*genetics ; }, abstract = {INTRODUCTION: HER-2/neu status determines the eligibility for targeted therapy with trastuzumab in breast carcinoma. Evaluation for HER-2/neu protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH) has become the gold standard.

AIMS: Since data on HER-2/neu assessment by IHC and FISH and studies regarding concordance between the results of the two techniques are limited, especially from India, we sought to study HER-2 gene amplification status by FISH in equivocal (2+) cases by IHC and also study aberrant signal patterns.

SETTINGS AND DESIGN: Mastectomies and breast core biopsies, equivocal for HER-2/neu protein expression, were analyzed for HER-2 amplification by FISH.

MATERIALS AND METHODS: IHC (DAKO) and FISH (PathVysion dual-probe system) tests were performed on 68 of 112 (after exclusion) 10% neutral buffered formalin (NBF)-fixed paraffin-embedded tissues and evaluated according to American Society of Clinical Oncology ASCO guidelines.

STATISTICAL ANALYSIS USED: Chi-square (χ2) test and the two-tailed P value were applied using Graphpad Quickcels software, version 2006.

RESULTS: It was found that 73.5% of the IHC 2+ patients were negative for HER-2/neu amplification, 25% were positive (ratios ranging from 2.3 to 5.6) and 1 patient was equivocal (2.2). Retesting FISH HER-2 equivocal case on another tumor block by IHC demonstrated HER-2 overexpression of protein 3+, thus resolving the equivocal status. Polysomy and HER-2 genetic heterogeneity were seen frequently.

CONCLUSIONS: The findings reiterate that IHC HER-2 equivocal cases are a heterogeneous group and need FISH for further categorization. Low concurrence (25%) rate between both IHC and FISH results in the equivocal scenario can be attributed to tumors with polysomy 17 and HER-2/neu genetic heterogeneity.}, } @article {pmid21934211, year = {2011}, author = {El-Attar, HA and Sheta, MI}, title = {Hepatocyte growth factor profile with breast cancer.}, journal = {Indian journal of pathology & microbiology}, volume = {54}, number = {3}, pages = {509-513}, doi = {10.4103/0377-4929.85083}, pmid = {21934211}, issn = {0974-5130}, mesh = {Adult ; Biomarkers, Tumor/blood ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal/*diagnosis/*pathology ; Female ; Hepatocyte Growth Factor/*analysis/*blood ; Humans ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: The multifunctional hepatocyte growth factor (HGF) is the ligand of c-Met receptor; it plays important role in mammary differentiation. HGF-Met signaling is a critical downstream function of c-Src-Stat3 pathway in mammalian tumorigenesis.

AIM: Evaluation of tissue c-Met receptor hepatocyte growth factor receptor (HGFR) and serum level of HGF in female breast ductal carcinoma.

MATERIALS AND METHODS: Sixty-eight premenopausal females were divided as 30 control females subdivided into: [Group 1] 15 healthy volunteer females and [Group 2] five with fibrocystic disease and 10 having fibroadenoma of the breast and patients group [Group 3] consisted of 38 female patients with breast ductal carcinoma. Thorough clinical examination, preoperative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine, and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level, before surgery and histopathological examination of the breast masses, and immunohistochemical detection of HGFR were done.

RESULTS AND CONCLUSIONS: Significant increase in serum HGF levels were found in patients with breast cancer as compared with controls. Significant increase was also seen in patients with breast cancer with and without lymph node metastasis when each subgroup was compared with controls. Serum level of HGF is an independent prognostic indicator of breast cancer. Fibrocystic disease of the breast showed weak HGFR expression, while in normal tissue, HGFR was scanty; meanwhile, breast invasive ductal carcinoma showed homogenous strong reaction to HGFR. HGF is only one of a number of key factors involved in breast cancer and preoperative high serum HGF levels and malignancy occur usually together.}, } @article {pmid21933790, year = {2011}, author = {Xia, Y and Jiang, S and Weng, S and Lv, X and Cheng, H and Fang, C}, title = {Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.}, journal = {Rheumatology (Oxford, England)}, volume = {50}, number = {12}, pages = {2187-2196}, doi = {10.1093/rheumatology/ker231}, pmid = {21933790}, issn = {1462-0332}, mesh = {Analysis of Variance ; Animals ; Antibodies, Antinuclear/*immunology ; Cytokines/biosynthesis ; DNA, Protozoan/*administration & dosage/immunology ; Dendritic Cells/*immunology ; Female ; Immunophenotyping ; Kidney Diseases/immunology/pathology/*prevention & control ; Lupus Erythematosus, Systemic/immunology/pathology/*prevention & control ; Mice ; Mice, Inbred BALB C ; Proteinuria/etiology ; Rats ; Rats, Wistar ; T-Lymphocytes/metabolism ; Trypanosoma/immunology ; Vaccines, DNA/*administration & dosage ; }, abstract = {OBJECTIVES: Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies.

METHODS: iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.}, } @article {pmid21932188, year = {2011}, author = {Ogawa, M and Kawaguchi, Y and Uchida, T and Ito, H and Mine, T}, title = {A case of small pancreatic cancer with intra-pancreatic metastasis diagnosed by endoscopic ultrasound.}, journal = {The Tokai journal of experimental and clinical medicine}, volume = {36}, number = {3}, pages = {75-78}, pmid = {21932188}, issn = {2185-2243}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/*diagnostic imaging/*metabolism/pathology/surgery ; Cholangiopancreatography, Endoscopic Retrograde ; *Endosonography ; Female ; Humans ; Pancreas/*diagnostic imaging/pathology/surgery ; Pancreatic Neoplasms/*diagnostic imaging/*metabolism/pathology/surgery ; Treatment Outcome ; }, abstract = {The usefulness of endoscopic ultrasound (EUS) in the diagnosis of small pancreatic cancer is widely accepted. We experienced a small, 8 mm, pancreatic cancer with intra-pancreatic metastasis of 2 mm revealed by EUS. The patient was a 71-year-old female with a small low echoic tumor observed by abdominal ultrasonography. She was referred to our hospital for further investigation. She complained of mild abdominal pain. She had a past history of myoma uteri. Ultrasonography showed a 10 mm low echoic mass in the body of the pancreas, but it was difficult to make a distinction between a solid mass and a cystic lesion. No tumor was shown by CT or MRI. EUS was performed, and showed a solid low echoic tumor of 8 mm and a low echoic mass of 2 mm in a diameter near the tumor. An ERCP study was performed, but the cytology of the normal main pancreatic duct was shown to be benign. We diagnosed the patient with pancreatic cancer, and surgery was performed. A pathological examination revealed a 10 mm invasive ductal carcinoma and intra-pancreatic metastasis.}, } @article {pmid21925246, year = {2011}, author = {Gabrovska, PN and Smith, RA and Tiang, T and Weinstein, SR and Haupt, LM and Griffiths, LR}, title = {Semaphorin-plexin signalling genes associated with human breast tumourigenesis.}, journal = {Gene}, volume = {489}, number = {2}, pages = {63-69}, doi = {10.1016/j.gene.2011.08.024}, pmid = {21925246}, issn = {1879-0038}, mesh = {Antigens, CD/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Adhesion Molecules/genetics/metabolism ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Membrane Proteins/*genetics/metabolism ; Neovascularization, Pathologic/genetics/metabolism ; Nerve Tissue Proteins/*genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface/*genetics/metabolism ; Semaphorins/*genetics/metabolism ; Signal Transduction ; }, abstract = {INTRODUCTION: Gene expression profiling has enabled us to demonstrate the heterogeneity of breast cancers. The potential of a tumour to grow and metastasise is partly dependant on its ability to initiate angiogenesis or growth and remodelling of new blood vessels, usually from a pre-existing vascular network, to ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells along with access to the systemic circulation. Cell-cell signalling of semaphorin ligands through interaction with their plexin receptors is important for the homeostasis and morphogenesis of many tissues and has been widely studied for a role in neural connectivity, cancer, cell migration and immune responses. This study investigated the role of four semaphorin/plexin signalling genes in human breast cancers in vivo and in vitro.

MATERIALS AND METHODS: mRNA was extracted from formalin fixed paraffin embedded archival breast invasive ductal carcinoma tissue samples of progressive grades (grades I-III) and compared to tissue from benign tumours. Gene expression profiles were determined by microarray using the Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays and validated by Q-PCR using a Corbett RotorGene 6000. Following validation, the gene expression profile of the identified targets was correlated with those of the human breast cancer cell lines MCF-7 and MDA-MD-231.

RESULTS: The array data revealed that 888 genes were found to be significantly (p≤0.05) differentially expressed between grades I and II tumours and 563 genes between grade III and benign tumours. From these genes, we identified four genes involved in semaphorin-plexin signalling including SEMA4D which has previously been identified as being involved in increased angiogenesis in breast cancers, and three other genes, SEMA4F, PLXNA2 and PLXNA3, which in the literature were associated with tumourigenesis, but not directly in breast tumourigenesis. The microarray analysis revealed that SEMA4D was significantly (P=0.0347) down-regulated in the grade III tumours compared to benign tumours; SEMA4F, was significantly (P=0.0159) down-regulated between grades I and II tumours; PLXNA2 was significantly (P=0.036) down-regulated between grade III and benign tumours and PLXNA3 significantly (P=0.042) up-regulated between grades I and II tumours. Gene expression of SEMA4D was validated using Q-PCR, demonstrating the same expression profile in both data sets. When the sample set was increased to incorporate more cases, SEMA4D continued to follow the same expression profile, including statistical significance for the differences observed and small standard deviations. In vitro the same pattern was present where expression for SEMA4D was significantly higher in MDA-MB-231 cells when compared to MCF-7 cells. The expression of SEMA4F, PLXNA2 and PLXNA3 could not be validated using Q-PCR, however in vitro analysis of these three genes revealed that both SEMA4F and PLXNA3 followed the microarray trend in expression, although they did not reach significance. In contrast, PLXNA2 demonstrated statistical significance and was in concordance with the literature.

DISCUSSION: We, and others, have proposed SEMA4D to be a gene with a potentially protective effect in benign tumours that contributes to tumour growth and metastatic suppression. Previous data supports a role for SEMA4F as a tumour suppressor in the peripheral nervous system but our data seems to indicate that the gene is involved in tumour progression in breast cancer. Our in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. Finally, our in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours.

CONCLUSIONS: Semaphorins and their receptors, the plexins, have been implicated in numerous aspects of neural development, however their expression in many other epithelial tissues suggests that the semaphorin-plexin signalling system also contributes to blood vessel growth and development. These findings warrant further investigation of the role of semaphorins and plexins and their role in normal and tumour-induced angiogenesis in vivo and in vitro. This may represent a new front of attack in anti-angiogenic therapies of breast and other cancers.}, } @article {pmid21922383, year = {2011}, author = {Yuri, T and Lai, YC and Kanematsu, S and Kuwata, M and Yoshizawa, K and Tsubura, A}, title = {Effects of short-term estrogen treatment on the progression of N-methyl-N-nitrosourea-induced premalignant mammary lesions in female Lewis rats.}, journal = {Medical molecular morphology}, volume = {44}, number = {3}, pages = {125-130}, pmid = {21922383}, issn = {1860-1499}, mesh = {Animals ; Antineoplastic Agents/pharmacology/*therapeutic use ; Cell Transformation, Neoplastic/*drug effects ; Cyclin D1/metabolism ; Estrogens/pharmacology/*therapeutic use ; Female ; Mammary Glands, Animal/drug effects/metabolism/pathology ; Mammary Neoplasms, Experimental/*chemically induced/*drug therapy/pathology ; Methylnitrosourea ; Precancerous Conditions/*chemically induced/*drug therapy/pathology ; Proliferating Cell Nuclear Antigen/metabolism ; Rats ; Rats, Inbred Lew ; }, abstract = {We studied the effects of short-term estrogen treatment (STET) on the progression of mammary lesions from ductal hyperplasia (DH) through ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) in the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis model. Three-week-old female Lewis rats (n = 40) received an intraperitoneal injection of MNU (50 mg/kg). Three weeks later, a 3-week-release, 0.25-mg, 17β-estradiol pellet was subcutaneously implanted for 2 weeks in 20 rats (STET); the remaining 20 rats did not receive the estradiol pellets (age-matched control). All rats were killed at 12 weeks of age, and their abdominal-inguinal mammary glands were histologically examined. The incidence and multiplicity of DHs were similar between groups (STET, 90% and 3.9 ± 0.6 vs. age-matched controls, 80% and 3.0 ± 0.5). However, DCIS and IDC did not develop in STET rats, whereas DCIS (25% and 1.4 ± 0.2) and IDC (35% and 1.4 ± 0.3) developed in the age-matched controls. Immunoscores of estrogen and progesterone receptors and positive rate of proliferative cell nuclear antigen (PCNA) in DH were similar in both groups, while the positive rate of cyclin D1 was significantly reduced in the STET group (P < 0.05). Thus, STET blocked the progression from DH to DCIS in MNU-induced mammary carcinogenesis, and decreased expression of cyclin D1 may play an important role in the blockade of cell transition from DH to DCIS.}, } @article {pmid21921327, year = {2011}, author = {Faghani, M and Ghasemi, FM and Nikhbakht, M and Salehi, M}, title = {TP53 PIN3 polymorphism associated with breast cancer risk in Iranian women.}, journal = {Indian journal of cancer}, volume = {48}, number = {3}, pages = {298-302}, doi = {10.4103/0019-509X.84925}, pmid = {21921327}, issn = {1998-4774}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics ; Carcinoma, Ductal/epidemiology/*genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Introns/genetics ; Iran ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Segmental Duplications, Genomic/genetics ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {BACKGROUND: Breast cancer is one of the most common cancers in Iranian women. The p53 gene plays a principal role in genomic stability, and its function varies according to polymorphisms. The aim of our study was to determine the relationship between the intron3 16bp duplication polymorphism of the p53 gene and breast cancer in Iranian women.

MATERIALS AND METHODS: We performed a case-control study among 145 patients with invasive ductal carcinoma of the breast and 145 controls in Isfahan, Iran. The distribution of the intron3 16bp duplication polymorphism was determined by polymerase chain reaction (PCR). The relationship between clinicopathological data and the PIN3 polymorphism was examined using chi-squared analysis.

RESULTS: A significant difference was observed in the polymorphism variants in breast cancer specimens compared with controls (P < .001). Among the cancer patients, 59.9% were below the age of 50 years; and 67.5% of the patients in this group had the intron3 16bp duplication polymorphism.

CONCLUSIONS: PIN3 Ins 16bp duplication polymorphism is a genetically predisposing factor for breast cancer development in Iranian women and may be causal in patients under the age of 50 years.}, } @article {pmid21919216, year = {2011}, author = {Siddiqui, FA and Maheshwari, V and Alam, K and Jain, A}, title = {Coexistent non-Hodgkins lymphoma and ductal carcinoma breast: diagnosis on fine needle aspiration cytology.}, journal = {Diagnostic cytopathology}, volume = {39}, number = {10}, pages = {767-769}, doi = {10.1002/dc.21547}, pmid = {21919216}, issn = {1097-0339}, mesh = {*Biopsy, Fine-Needle ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Epithelial Cells/pathology ; Female ; Humans ; Lymphocytes/pathology ; Lymphoma, Non-Hodgkin/diagnosis/pathology ; Middle Aged ; }, abstract = {Synchronous occurrance of multiple neoplastic processes is not very common, and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by non-Hodgkins lymphoma is a rare event and primary breast non-Hodgkins lymphoma is even rarer. The authors take this opportunity to report a case of primary B-cell non-Hodgkins lymphoma breast occurring in association with invasive ductal carcinoma in a 47-year-old female for its rare synchronous association.}, } @article {pmid21914346, year = {2011}, author = {Hao, JY and Yang, YL and Li, S and Qian, XL and Liu, FF and Fu, L}, title = {[PSCA expression in invasive micropapillary carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {40}, number = {6}, pages = {382-386}, pmid = {21914346}, issn = {0529-5807}, mesh = {Antigens, Neoplasm/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Papillary/genetics/*metabolism/pathology ; Female ; GPI-Linked Proteins/genetics/metabolism ; Humans ; *Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics/*metabolism ; Neoplasm Staging ; RNA, Messenger/metabolism ; }, abstract = {OBJECTIVE: To study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features.

METHODS: The expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject.

RESULTS: Immunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P = 0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P = 0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue.

CONCLUSION: PSCA might play an important role in lymph node metastasis in IMPC.}, } @article {pmid21913809, year = {2012}, author = {Erdogan, D and Tayyar, S and Icli, A and Uysal, BA and Varol, E and Ozaydin, M and Dogan, A}, title = {Elevated mean platelet volume is associated with impaired coronary microvascular function in patients with idiopathic dilated cardiomyopathy.}, journal = {Platelets}, volume = {23}, number = {3}, pages = {177-183}, doi = {10.3109/09537104.2011.611273}, pmid = {21913809}, issn = {1369-1635}, mesh = {Adult ; Aged ; *Blood Platelets ; Cardiomyopathy, Dilated/*blood/diagnostic imaging ; Coronary Circulation ; Coronary Vessels/physiopathology/ultrastructure ; Echocardiography ; Female ; Heart Failure/*blood/diagnostic imaging/physiopathology ; Humans ; Male ; Microvessels/diagnostic imaging/physiopathology ; Middle Aged ; *Myocardium ; Ventricular Dysfunction, Left/*blood/diagnostic imaging/physiopathology ; }, abstract = {Attenuated coronary flow reserve (CFR) has been reported in patients with idiopathic dilated cardiomyopathy (IDC). On the other hand increased platelet activity has been demonstrated in patients with congestive heart failure and left ventricular dysfunction. Accordingly, we aimed to investigate whether mean platelet volume (MPV) is increased in patients with IDC and increased MPV correlates with the degree of coronary microvascular dysfunction. MPV was measured in 37 patients with IDC. Each patient with IDC also underwent echocardiographic examination including CFR measurement. Patients with IDC were divided into two groups based on median CFR value (lower CFR group and normal CFR group). MPV was significantly higher in the lower CFR group than in the normal CFR group (9.00 ± 0.56 vs. 8.25 ± 0.76 fl; respectively, p = 0.001). CFR correlated significantly and inversely to MPV (r = -0.475, p = 0.003). Logistic regression analysis revealed that MPV level was the independent predictor of lower CFR (β = -0.750, p = 0.002). Furthermore, MPV was an accurate predictor of low CFR (p = 0.001); Area under the curve was 82% (95% CI 0.67-0.96). The best cut-off value of MPV to predict low CFR was 8.3 fl with 95% sensitivity and 69% specificity. In conclusion, the present study showed a negative correlation between MPV and CFR in patients with IDC.}, } @article {pmid21913743, year = {2011}, author = {Dong, SW and Wang, L and Sui, J and Deng, XY and Chen, XD and Zhang, ZW and Liu, X and Liu, ZM and Zhang, JH and Yang, QS and Jia, YF and Song, X}, title = {Expression patterns of ER, HER2, and NM23-H1 in breast cancer patients with different menopausal status: correlations with metastasis.}, journal = {Molecular diagnosis & therapy}, volume = {15}, number = {4}, pages = {211-219}, pmid = {21913743}, issn = {1179-2000}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/secondary ; Female ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; *Menopause ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases/*metabolism ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {OBJECTIVE: This study was designed to analyze expression patterns of estrogen receptor (ER), human epidermal growth factor receptor-2 (HER2/ERBB2), and nonmetastatic protein 23 (NM23-H1/NME1) proteins in patients with invasive ductal carcinoma and different menopausal status to identify their relationships with axillary lymph node metastasis.

MATERIALS AND METHODS: 213 pre-menopausal and 177 post-menopausal women diagnosed with invasive ductal carcinoma were evaluated for ER, HER2, and NM23-H1 protein expression by immunohistochemistry. When HER2 immunoreactivity was equivocal (category 2+), specimens were confirmed by fluorescence in situ hybridization.

RESULTS: ER expression showed no correlation with menopausal status or lymph node metastasis (each p > 0.05). However, expression of ER was associated with negative expression of HER2 (r = -0.214, p < 0.05) and positive expression of NM23-H1 (r = 0.137, p < 0.05) in the pre-menopausal group. Over-expression of HER2 was correlated with menopausal status (r = -0.107, p < 0.05) and lymph node metastasis in the ER-negative post-menopausal group (r = 0.222, p < 0.05). NM23-H1 was associated with less lymph node metastasis in the ER-positive pre-menopausal group (r = -0.237, p < 0.05).

CONCLUSION: Our results indicated that expression patterns of ER, NM23-H1, and HER2 in primary breast cancer lesions warn that cells might have metastatic potential, which could assist clinicians to provide a more accurate prognosis and tailor therapeutic management for individual patients.}, } @article {pmid21913022, year = {2012}, author = {Fortunato, L and Mascaro, A and Poccia, I and Andrich, R and Amini, M and Costarelli, L and Cortese, G and Farina, M and Vitelli, C}, title = {Lobular breast cancer: same survival and local control compared with ductal cancer, but should both be treated the same way? analysis of an institutional database over a 10-year period.}, journal = {Annals of surgical oncology}, volume = {19}, number = {4}, pages = {1107-1114}, doi = {10.1245/s10434-011-1907-9}, pmid = {21913022}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/*mortality/pathology/*surgery ; Carcinoma, Lobular/*mortality/pathology/*surgery ; Chemoradiotherapy, Adjuvant ; Cohort Studies ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Mastectomy/mortality/statistics & numerical data ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local/mortality/surgery ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is believed to be more often multicentric and bilateral compared with invasive ductal cancer (IDC), leading clinicians to pursue a more aggressive local and contralateral approach.

METHODS: Retrospective review of a consecutive cohort of breast cancer patients operated at one institution from January 2000 to January 2010 was performed. Median follow-up was 4 years.

RESULTS: There were 171 ILC (14.5%) and 1,011 IDC patients in the study period. Median age (63 vs. 65 years) and tumor diameter (1.7 cm) were similar in the two groups. Diagnoses of ILC were more frequent in the second half of the study period (55/465 vs. 116/662, p<0.01). Multicentricity was reported in 108/1,011 (10.6%) IDC and in 31/171 (18.1%) ILC patients (p<0.01). A positive margin of resection at initial surgery was documented in 71/1,011 (7%) IDC and in 21/171 (12.3%) ILC patients (p<0.001). Although the rate of mastectomy decreased over time in both groups, this was more pronounced for ILC patients (p<0.001). Locoregional control, contralateral cancer, overall survival, disease-free survival, and survival according to diameter, nodal status, and type of surgical intervention did not differ between IDC and ILC. On multivariate analysis, stage of disease and hormone receptor status were associated with disease-free survival, but histology was not.

CONCLUSIONS: Although ILC is more often multicentric, bilateral, and associated with a positive margin of resection, local control and survival are similar to IDC. ILC can be treated similarly to IDC with good results.}, } @article {pmid21912344, year = {2011}, author = {Schnitzler, C and Brazier, T and Button, C and Seifert, L and Chollet, D}, title = {Effect of velocity and added resistance on selected coordination and force parameters in front crawl.}, journal = {Journal of strength and conditioning research}, volume = {25}, number = {10}, pages = {2681-2690}, doi = {10.1519/JSC.0b013e318207ef5e}, pmid = {21912344}, issn = {1533-4287}, mesh = {Arm/physiology ; Athletes ; Biomechanical Phenomena/physiology ; Humans ; Male ; Muscle Strength/*physiology ; Muscle, Skeletal/physiology ; Psychomotor Performance/*physiology ; *Resistance Training ; Swimming/*physiology ; }, abstract = {The effect of (a) increasing velocity and (b) added resistance was examined on the stroke (stroke length, stroke rate [SR]), coordination (index of coordination [IdC], propulsive phases), and force (impulse and peaks) parameters of 7 national-level front crawl swimmers (17.14 ± 2.73 years of swimming; 57.67 ± 1.62 seconds in the 100-m freestyle). The additional resistance was provided by a specially designed parachute. Parachute swimming (PA) and free-swimming (F) conditions were compared at 5 velocities per condition. Video footage was used to calculate the stroke and coordination parameters, and sensors allowed the determination of force parameters. The results showed that (a) an increase in velocity (V) led to increases in SR, IdC, propulsive phase duration, and peak propulsive force (p < 0.05), but no significant change in force impulse per cycle, whatever the condition (PA or F); and (b) in PA conditions, significant increases in the IdC, propulsive phase duration, and force impulse and a decrease in SR were recorded at high velocities (p < 0.05). These results indicated that, in the F condition, swimmers adapted to the change in velocity by modifying stroke and coordination rather than force parameters, whereas the PA condition enhanced the continuity of propulsive action and force development. Added resistance, that is, "parachute training," can be used for specific strength training purposes as long as swimming is performed near maximum velocity.}, } @article {pmid21910568, year = {2011}, author = {Baltatzis, GE and Voloudakis, GE and Arnogiannakis, N and Misitzis, J and Voloudakis-Baltatzis, IE}, title = {Differential diagnosis between sclerosing adenosis and tubular carcinoma of the breast under transmission and scanning electron microscope.}, journal = {Ultrastructural pathology}, volume = {35}, number = {5}, pages = {226-229}, doi = {10.3109/01913123.2011.603460}, pmid = {21910568}, issn = {1521-0758}, mesh = {Adenocarcinoma/*diagnosis/ultrastructure ; Breast Neoplasms/*diagnosis/ultrastructure ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/*diagnosis/ultrastructure ; Humans ; Microscopy, Electron, Scanning/*methods ; Microscopy, Electron, Transmission/*methods ; Sclerosis ; }, abstract = {The tubular carcinoma of the breast is an uncommon histological subtype of invasive breast cancer, which is generally associated with an excellent prognosis. Previous studies have demonstrated that this well differentiated variant is linked with a low incidence of lymph node involvement, a low rate of local recurrence and a high overall survival rate when compared to standard invasive ductal carcinoma. Due to its favorable prognosis, some studies have proposed that a diagnosis of tubular carcinoma might warrant less aggressive surgical or adjuvant treatment. Histologically, tubular carcinoma may mimic sclerosing adenoma or bluntduct adenosis. Its ductal nature appears well confirmed by the few ultrastructural studies of this mammary cancer. Tubular carcinoma should also be distinguished from microglandular adenosis, an uncommon form of sclerosing adenosis. The aim of this study is to prove that the ultrastructure results can give the correct diagnosis between tubular carcinoma and sclerosing adenosis.}, } @article {pmid21909787, year = {2011}, author = {Mao, XY and Fan, CF and Wei, J and Liu, C and Zheng, HC and Yao, F and Jin, F}, title = {Increased N-myc downstream-regulated gene 1 expression is associated with breast atypia-to-carcinoma progression.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {32}, number = {6}, pages = {1271-1276}, pmid = {21909787}, issn = {1423-0380}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/biosynthesis ; Blotting, Western ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Cell Cycle Proteins/*biosynthesis ; Disease Progression ; Epithelium/metabolism/pathology ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Young Adult ; }, abstract = {N-myc downstream-regulated gene-1 (NDRG1) has been identified as a protein involved in the differentiation of epithelial cells. As a newly metastasis suppressor gene, whether it contributes to carcinogenesis of breast cancer is still unknown. This study aimed to clarify the possible role of NDRG1 for breast cancer carcinogenesis, and further to investigate its clinicopathological significance in invasive breast cancer. We examined the expression of NDRG1 in normal epithelium of breast (n = 35), usual ductal hyperplasia (n = 22), atypical ductal hyperplasia (n = 33), atypical lobular hyperplasia (n = 8), ductal carcinoma in situ (n = 16), lobular carcinoma in situ (n = 6), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 45) by immunohistochemistry and analyzed the correlation between NDRG expression and clinicopathological features of invasive breast cancer. Western blot analysis was carried out to investigate the expression of NDRG1 in 20 invasive ductal breast cancer and the paired non-tumor portion of the same case. NDRG1 expression in invasive breast cancer (70/95, 73.7%) was higher than that in noninvasive breast lesions (29/85, 34.1%; p < 0.05) which was higher than that in normal breast epithelium (5/35, 14.3%; p < 0.05). Statistical analysis revealed a significant correlation between NDRG1 expression with tumor stage in invasive breast cancer, and its expression in invasive ductal carcinoma is significantly higher than invasive lobular carcinoma (p < 0.05). It was not associated with age, menopausal status, tumor size, and lymph node metastasis. NDRG1 protein levels were significantly higher in invasive ductal breast cancer compared to the paired non-tumor portion of the same case by Western blot analysis (p < 0.05). Increased NDRG-1 expression is associated with breast atypia-to-carcinoma progression. NDRG1 expression might participate in the carcinogenesis and progression of invasive breast cancer. These findings provide further evidence that NDRG1 may serve as an important biomarker for invasive breast cancer.}, } @article {pmid21906715, year = {2011}, author = {Munhoz, AM and Pellarin, L and Montag, E and Filassi, JR and Tachibana, A and Gebrim, H and Gemperli, R and Ferreira, MC}, title = {Superficial inferior epigastric artery (SIEA) free flap using perforator vessels as a recipient site: clinical implications in autologous breast reconstruction.}, journal = {American journal of surgery}, volume = {202}, number = {5}, pages = {612-617}, doi = {10.1016/j.amjsurg.2010.11.018}, pmid = {21906715}, issn = {1879-1883}, mesh = {Angiography/methods ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/surgery ; Epigastric Arteries/diagnostic imaging/*transplantation ; Female ; Free Tissue Flaps/*blood supply ; Humans ; Mammaplasty/*methods ; Mammary Arteries/*surgery ; Mastectomy ; Middle Aged ; Multidetector Computed Tomography ; Transplant Donor Site/surgery ; Transplantation, Autologous ; }, abstract = {BACKGROUND: Breast reconstruction with autogenous tissue is a well-established technique, but there are some limitations related to donor-site morbidity. Among available techniques, the superficial inferior epigastric artery (SIEA) flap is the least invasive procedure because it does not require harvesting or incision of the rectus muscle or the abdominal fascia. Besides adequate flap choice, the proper selection of the recipient vessels is an important factor. Thus, the internal mammary perforator branches (IMPBs) have been an attractive option regarding recipient pedicle morbidity.

METHODS: The investigators reported the use of the free SIEA flap with the IMPBs as a recipient site to reconstruct radical mastectomy.

RESULTS: Five patients with invasive ductal carcinoma underwent modified radical mastectomy and reconstruction. The IMPBs were selected as the recipient site and a free SIEA flap was used. The donor defect was closed directly without synthetic mesh. Satisfactory breast shape was achieved, and no complications were observed.

CONCLUSIONS: For selected patients, the SIEA flap and IMPBs may constitute a new alternative for immediate breast reconstruction, because of the possibility of large tissue transfer with minimal donor and recipient area morbidity. The SIEA pedicle size and the quality of IMPB vessels should be carefully evaluated.}, } @article {pmid21901326, year = {2011}, author = {Takahashi, Y and Kaneoka, Y and Maeda, A and Isogai, M}, title = {Distal pancreatectomy with celiac axis resection for carcinoma of the body and tail of the pancreas.}, journal = {World journal of surgery}, volume = {35}, number = {11}, pages = {2535-2542}, pmid = {21901326}, issn = {1432-2323}, mesh = {Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Carcinoma, Pancreatic Ductal/mortality/pathology/*surgery ; Celiac Plexus/*surgery ; Female ; Follow-Up Studies ; Ganglia, Sympathetic/surgery ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: We retrospectively investigated our experiences with distal pancreatectomy with celiac axis resection (DP-CAR) for locally advanced pancreatic cancer and compared the operative outcome and long-term survival between DP-CAR and standard distal pancreatectomy (DP). Although several authors reported that DP-CAR increases resectability rates, the long-term results of this operation are not clear, and there are few reports presenting a comparison of the short- and long-term results between DP-CAR and DP.

METHODS: From 1993 to 2010, 43 patients with invasive ductal carcinoma of the body or tail of the pancreas underwent a macroscopically curative resection (R0/1). Sixteen patients underwent DP-CAR and 27 patients underwent DP. No DP-CAR patients underwent any preoperative coil embolization of the common hepatic artery (CHA) to stimulate the development of collateral pathways from the superior mesenteric artery. The perioperative and histopathologic parameters and survival data were analyzed to compare the two operations.

RESULTS: There was no difference in mean operative time, mean blood loss, postoperative mortality, and morbidity between DP-CAR and DP. The rates of morbidity and in-hospital mortality of DP-CAR were 56 and 6%, respectively. In DP-CAR, 15 patients did not require reconstruction of the hepatic artery and no hepatic infarctions were clinically encountered after surgery. The estimated overall 1- and 3-year survival rates in patients who underwent DP-CAR were 42.6 and 25.6%, respectively, and their survival time was significantly less than that of patients who underwent DP (median survival time: 9.7 vs. 30.9 months, P = 0.033). The R1 resection rates of these groups were 44% in DP-CAR and 22% in DP, respectively.

CONCLUSION: DP-CAR is a safe and rational procedure for locally advanced pancreatic cancer without preoperative embolization of the CHA. Although the short-term results were equivalent to that for DP, DP-CAR did not improve the long-term survival because of the high rate of R1 resection at present.}, } @article {pmid21891999, year = {2011}, author = {Hasebe, O and Ochi, Y and Hara, E and Suzawa, K and Seki, A and Nagaya, T and Tatai, T and Jimbo, Y and Hosaka, N}, title = {[A case of metachronous invasive ductal carcinoma concomitant with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas, which could not be detected in contrast-enhanced CT scan performed 3 months ago].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {108}, number = {9}, pages = {1579-1588}, pmid = {21891999}, issn = {0446-6586}, mesh = {Adenocarcinoma, Mucinous/diagnostic imaging/*pathology ; Carcinoma, Pancreatic Ductal/diagnostic imaging/*pathology ; Humans ; Male ; Middle Aged ; Neoplasms, Second Primary/diagnostic imaging/*pathology ; Pancreatic Neoplasms/diagnostic imaging/*pathology ; Tomography, X-Ray Computed ; }, abstract = {A 61-year-old man had been followed up in another hospital under diagnosis of branch duct type IPMN for 4 years. Contrast-enhanced CT scan for regular check performed 3 months ago revealed no increase of IPMN and no pancreatic tumor. However, he complained of back pain after that, MRI was performed. It revealed a solid tumor in size of 25mm diameter at the head of pancreas. The tumor was apparent from IPMN in several imaging modalities. Pancreatoduodenectomy was performed under diagnosis of invasive ductal carcinoma concomitant with IPMN. Post-operative pathological findings revealed IPMN was adenoma with mild atypia, and solid tumor was diagnosed invasive ductal carcinoma with solitary minute liver metastasis.}, } @article {pmid21882089, year = {2011}, author = {Kim, SH and Cha, ES and Park, CS and Kang, BJ and Whang, IY and Lee, AW and Song, BJ and Park, J}, title = {Imaging features of invasive lobular carcinoma: comparison with invasive ductal carcinoma.}, journal = {Japanese journal of radiology}, volume = {29}, number = {7}, pages = {475-482}, pmid = {21882089}, issn = {1867-108X}, mesh = {Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/pathology ; Chi-Square Distribution ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: The aim of this study was to evaluate the imaging findings of invasive lobular carcinoma (ILC) compared to those of invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: The study included ILCs (n = 27) and IDCs (n = 85). Imaging findings were retrospectively evaluated, according to the BI-RADS lexicon. We compared the imaging findings, multiplicity, and magnetic resonance imaging (MRI) detection accuracy of ILC with those of IDC.

RESULTS: At mammography, normal findings and mass lesions were more frequent with ILCs (14.8% and 59.2%, respectively) than with IDCs (1.2% and 44.7%, respectively) (P = 0.009). With ultrasonography (US), posterior acoustic shadowing was more frequently seen in ILCs (59.2%) than in IDCs (15.8%) (P < 0.001). With MRI, both ILCs and IDCs most commonly appeared as a heterogeneously enhancing, irregular mass with a spiculated border. Multifocality was more frequently associated with ILCs (40.7%) than with IDCs (14.1% 1% 0.002). However, multicentricity and bilaterality were not different between the two groups. The sensitivity and specificity of MRI for the detection of multiplicity were 91.6% and 73.3%, respectively, for ILCs and 83.3% and 80.3%, respectively, for IDCs.

CONCLUSION: Normal findings, mass lesions on mammography, and posterior acoustic shadowing on US were more frequently associated with ILCs than with IDCs. Multifocality was more prevalent with ILCs than with IDCs.}, } @article {pmid21881484, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Kinoshita, T and Tsuda, H}, title = {Important histologic outcome predictors for patients with invasive ductal carcinoma of the breast.}, journal = {The American journal of surgical pathology}, volume = {35}, number = {10}, pages = {1484-1497}, doi = {10.1097/PAS.0b013e318224ca28}, pmid = {21881484}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/mortality/therapy ; Carcinoma, Ductal, Breast/*diagnosis/mortality/secondary/therapy ; Combined Modality Therapy ; Female ; Fibrosis/pathology ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Predictive Value of Tests ; Survival Rate ; Young Adult ; }, abstract = {The pathologic diagnosis is regarded as the final diagnosis of a disease, and pathologic examination based on tumor histology is very important for the accurate assessment of the biological characteristics of tumors. The purpose of this study was to investigate the histologic factors that accurately predict patient outcome among 1042 patients with invasive ductal carcinoma of the breast. Both well-known histologic factors and our proposed histologic factors were examined according to several tumor statuses using multivariate analysis. This study clearly demonstrated that type 4 invasive ductal carcinomas having fibrotic foci and atypical tumor-stromal fibroblasts within the fibrotic foci are significant outcome predictors for lymph node-negative and lymph node-positive, the pathologic UICC-TNM stage II and III, luminal A-subtype, luminal B-subtype, and equivocal HER2 subtype invasive ductal carcinoma patients. Lymph vessel tumor embolus grades 2 and 3 were significant outcome predictors for lymph node-positive, UICC pTNM stages II and III, luminal A-subtype, and triple-negative invasive ductal carcinoma patients (except lymph vessel tumor embolus grade 2 in luminal A-subtype patients). More than 5 mitotic figures in metastatic carcinoma to the lymph nodes was a significant outcome predictor for lymph node-positive, UICC pTNM stage II, and luminal A-subtype invasive ductal carcinoma patients. A fibrotic focus diameter >8 mm was a significant outcome predictor for UICC pTNM stages I and III invasive ductal carcinoma patients. These findings strongly suggest that these histologic factors are very useful for accurately predicting the outcomes of patients with invasive ductal carcinoma of the breast.}, } @article {pmid21880185, year = {2011}, author = {Chen, SF and Gong, C and Luo, M and Yao, HR and Zeng, YJ and Su, FX}, title = {Ubc9 expression predicts chemoresistance in breast cancer.}, journal = {Chinese journal of cancer}, volume = {30}, number = {9}, pages = {638-644}, pmid = {21880185}, issn = {1000-467X}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/drug therapy/*enzymology/pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*enzymology/pathology/surgery ; Cyclophosphamide/therapeutic use ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Proportional Hazards Models ; Remission Induction ; Tumor Burden ; Ubiquitin-Conjugating Enzymes/*metabolism ; Up-Regulation ; }, abstract = {Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (Χ[2] = 6.538, P = 0.038), larger tumor size (Χ[2] = 4.701, P = 0.030), advanced clinical stage (Χ[2] = 4.651, P = 0.031), lymph node metastasis (Χ[2] = 9.913, P = 0.010), basal-like phenotype (Χ[2] = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (Χ[2] = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (Χ[2] = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.}, } @article {pmid21875486, year = {2011}, author = {Wang, J and Wang, L and Liu, FF and Ma, YJ and Fu, L and Li, WL and Gu, F}, title = {[Robo1 expression in breast cancer and its relationship to brain metastasis].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {33}, number = {6}, pages = {447-451}, pmid = {21875486}, issn = {0253-3766}, mesh = {Adult ; Age Factors ; Aged ; Brain Neoplasms/*secondary ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/metabolism/secondary/surgery ; Female ; Fibroadenoma/metabolism ; Follow-Up Studies ; Humans ; Middle Aged ; Nerve Tissue Proteins/*metabolism ; Receptors, Immunologic/*metabolism ; Survival Rate ; }, abstract = {OBJECTIVE: To detect the expression of Robo1 in different breast tumors and its association with the breast cancer brain metastasis.

METHODS: Labelled streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma.

RESULTS: The expression pattern of Robo1 in DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma (87.0%, P < 0.05). The expression of Robo1 in IDC with brain metastasis (12.5%) was significantly lower than that in IDC without brain metastasis (56.3%, P < 0.05). The expression of Robo1 was much higher in more than 50 year-old-group (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The overall survival time in patients with the Robo1 negative expression was significantly shorter than those with positive expression (P < 0.05). No correlation was found between the Robo1 expression and the tumor size, lymph node metastasis, pathologic stage, histological grade and clinical stage (P > 0.05).

CONCLUSIONS: The Robo1 expression correlates negatively with IDC brain metastasis, and correlates positively with the age and prognosis of IDC patients. Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain metastasis.}, } @article {pmid21874750, year = {2011}, author = {Teoh, KH and Looi, LM and Sabaratnam, S and Cheah, PL and Nazarina, AR and Mun, KS}, title = {An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development.}, journal = {The Malaysian journal of pathology}, volume = {33}, number = {1}, pages = {35-42}, pmid = {21874750}, issn = {0126-8635}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Histology/standards ; Hospitals ; Humans ; Malaysia ; Medical Oncology/standards ; Middle Aged ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Research Design ; Retrospective Studies ; }, abstract = {Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.}, } @article {pmid21872255, year = {2011}, author = {Gutiérrez Valencia, TM and García de Llasera, MP}, title = {Determination of organophosphorus pesticides in bovine tissue by an on-line coupled matrix solid-phase dispersion-solid phase extraction-high performance liquid chromatography with diode array detection method.}, journal = {Journal of chromatography. A}, volume = {1218}, number = {39}, pages = {6869-6877}, doi = {10.1016/j.chroma.2011.08.011}, pmid = {21872255}, issn = {1873-3778}, mesh = {Animals ; Cattle ; Chromatography, High Pressure Liquid/instrumentation/*methods ; Liver/chemistry ; Lung/chemistry ; Methanol/chemistry ; Miniaturization ; Muscles/chemistry ; Organothiophosphorus Compounds/*analysis/isolation & purification ; Pesticide Residues/*analysis/isolation & purification ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction/*methods ; Tissue Distribution ; }, abstract = {A miniaturized method based on matrix solid-phase dispersion coupled to solid phase extraction and high performance liquid chromatography with diode array detection (MSPD-SPE-HPLC/DAD) was developed for the trace simultaneous determination of the following organophosphorus pesticides (OPPs) in bovine tissue: parathion-methyl, fenitrothion, parathion, chlorfenvinphos, diazinon, ethion, fenchlorphos, chlorpyrifos and carbophenothion. To perform the coupling between MSPD and SPE, 0.05 g of sample was dispersed with 0.2 g of C(18) silica sorbent and packed into a stainless steel cartridge containing 0.05 g of silica gel in the bottom. After a clean-up of high and medium polarity interferences with water and an acetonitrile:water mixture, the OPPs were desorbed from the MSPD cartridge with pure acetonitrile and directly transferred to a dynamic mixing chamber for dilution with water and preconcentration into an SPE 20 mm × 2.0 mm I.D. C(18) silica column. Subsequently, the OPPs were eluted on-line with the chromatographic mobile phase to the analytical column and the diode array detector for their separation and detection, respectively. The method was validated and yielded recovery values between 91% and 101% and precision values, expressed as relative standard deviations (RSD), which were less than or equal to 12%. Linearity was good and ranged from 0.5 to 10 μg g(-1), and the limits of detection of the OPPs were in the range of 0.04-0.25 μg g(-1). The method was satisfactorily applied to the analysis of real samples and is recommended for food control, research efforts when sample amounts are limited, and laboratories that have ordinary chromatographic instrumentation.}, } @article {pmid21868554, year = {2011}, author = {Wojnar, A and Pula, B and Piotrowska, A and Jethon, A and Kujawa, K and Kobierzycki, C and Rys, J and Podhorska-Okolow, M and Dziegiel, P}, title = {Correlation of intensity of MT-I/II expression with Ki-67 and MCM-2 proteins in invasive ductal breast carcinoma.}, journal = {Anticancer research}, volume = {31}, number = {9}, pages = {3027-3033}, pmid = {21868554}, issn = {1791-7530}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal/*metabolism/pathology ; Cell Cycle Proteins/*metabolism ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Metallothionein/*metabolism ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Neoplasm Invasiveness ; Nuclear Proteins/*metabolism ; }, abstract = {The purpose of the study was to evaluate the clinical significance of the intensity of metallothionein (MT-I/II) expression and its relationship to two different proliferation markers, Ki-67 antigen and minichromosome maintaince 2 protein (MCM-2) in 117 patients with invasive ductal breast carcinoma (IDC). A significantly higher MT-I/II expression was noted in the grade 3 (G3) carcinomas as compared to those of G1 and G2. A positive correlation was observed between the MT-I/II expression and both proliferation markers, Ki-67 (r=0.20, p=0.0343) and MCM-2 (r=0.25, p=0.0065). Also a strong positive correlation was noted between Ki-67 and MCM-2 expression (r=0.52, p<0.0001). No significant correlations were found between the analyzed markers and tumour size, lymph node metastasis, oestrogen expression (ER), progesterone receptor (PR) or human epidermal growth-factor receptor (HER-2) expression. Out of the three studied markers only the high expression of Ki-67 exhibited a negative impact on patient overall and event free survival and was an independent prognostic factor. MT-I/II and MCM-2 protein expression was not correlated with poor patient outcome, although MCM-2 expression correlated (Fisher's exact test) positively with grade of malignancy (p=0.0018) and negatively with ER (p=0.0002) and PR (p=0.0056) expression. To conclude, MT-I/II may play a key role in IDC proliferation, but is not a useful prognostic factor of this disease.}, } @article {pmid21867691, year = {2011}, author = {Suhane, S and Berel, D and Ramanujan, VK}, title = {Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.}, journal = {Biochemical and biophysical research communications}, volume = {412}, number = {4}, pages = {590-595}, pmid = {21867691}, issn = {1090-2104}, support = {R21 CA124843/CA/NCI NIH HHS/United States ; R21 CA124843-01A2/CA/NCI NIH HHS/United States ; R21-CA124843/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/enzymology/mortality/*pathology ; Carcinoma/enzymology/*pathology ; Female ; Humans ; Mitochondria/*enzymology ; NADH Dehydrogenase/genetics/*metabolism ; Neoplasm Invasiveness ; RNA, Small Interfering/genetics ; }, abstract = {We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.}, } @article {pmid21865662, year = {2011}, author = {Farag, FF and Martens, FM and Feitz, WF and Heesakkers, JP}, title = {Feasibility of noninvasive near-infrared spectroscopy to diagnose detrusor overactivity.}, journal = {Urologia internationalis}, volume = {87}, number = {3}, pages = {330-335}, doi = {10.1159/000329282}, pmid = {21865662}, issn = {1423-0399}, mesh = {Adult ; Aged ; Body Mass Index ; Feasibility Studies ; Hemodynamics ; Humans ; Male ; Middle Aged ; Spectroscopy, Near-Infrared/*methods ; Urinary Bladder/pathology ; Urinary Bladder, Overactive/*diagnosis ; Urination ; Urodynamics ; Urology/*methods ; }, abstract = {INTRODUCTION: Near-infrared spectroscopy (NIRS) is an optical technology able to detect the hemodynamic changes in biological tissues. Our objective was to determine the feasibility of applying NIRS in the noninvasive diagnosis of detrusor overactivity (DO).

PATIENTS AND METHODS: Comparative analysis was performed on 39 involuntary detrusor contractions (IDC) from 23 filling cystometries with simultaneous noninvasive NIRS of the bladder in 14 patients with DO. Motion artifacts were checked for via surface EMG of the abdominal muscles.

RESULTS: Thirty-nine IDC were obtained. The median amplitude of rise in detrusor pressure at DO was 48 cm H(2)O (range: 5-219). The median filling volume at DO was 148 ml (range: 9-531). NIRS curves demonstrated apparently significant deviations from baseline in 35 of 39 (90%) DO episodes. All onsets of NIRS deviations occurred within the time period of the IDC with a mean delay of 3 s (range: 0-9).

CONCLUSION: NIRS can be a potential tool for the noninvasive diagnosis of DO.}, } @article {pmid21864818, year = {2011}, author = {Matsumoto, K and Tanaka, H and Okajima, K and Hayashi, T and Kajiya, T and Kawai, H and Hirata, K}, title = {Relation between left ventricular morphology and reduction in functional mitral regurgitation by cardiac resynchronization therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {108}, number = {9}, pages = {1327-1334}, doi = {10.1016/j.amjcard.2011.06.052}, pmid = {21864818}, issn = {1879-1913}, mesh = {Aged ; *Cardiac Resynchronization Therapy ; Cardiomyopathy, Dilated/*therapy ; Case-Control Studies ; Echocardiography, Doppler, Color ; Female ; Follow-Up Studies ; Heart Ventricles/*diagnostic imaging ; Humans ; Male ; Mitral Valve/diagnostic imaging ; Mitral Valve Insufficiency/diagnostic imaging/*therapy ; Multivariate Analysis ; Papillary Muscles/diagnostic imaging ; *Ventricular Remodeling ; }, abstract = {The presence of functional mitral regurgitation (MR) is considered a significant risk factor for poor clinical prognosis in patients with idiopathic dilated cardiomyopathy (IDC). The objectives of this study were to test the hypothesis that not only global but also local left ventricular (LV) remodeling, including the position of the papillary muscles, may contribute to the development of MR in patients with IDC and wide QRS durations and can be reversed with cardiac resynchronization therapy (CRT). Eighty-four subjects were studied, 44 patients with IDC who underwent CRT and 40 age- and gender-matched controls. The position of the posteromedial papillary muscle was similar in the 2 groups, whereas the position of the anterolateral papillary muscle in patients with IDC was displaced more posteriorly than in controls. Multivariate analysis revealed that reduction in coaptation height (β = 0.44, p <0.001) and LV dyssynchrony by speckle-tracking radial strain (β = 0.303, p <0.01) were independent determinants of reduction in MR 5 ± 2 days after CRT; in contrast, restoration of the position of the posteriorly displaced anterolateral papillary muscle (β = 0.50, p <0.001) and the increase in sphericity index (β = 0.440, p <0.001) were identified as independent determinants of reduction in MR 6 ± 1 months after CRT. In conclusion, asymmetric local LV remodeling was observed at baseline, and asymmetric local LV reverse remodeling was observed at long-term follow-up after CRT in patients with IDC. Furthermore, different parameters contribute to the reduction in MR observed at short- and long-term follow-up after CRT.}, } @article {pmid21863360, year = {2012}, author = {Hata, S and Sakamoto, Y and Yamamoto, Y and Nara, S and Esaki, M and Shimada, K and Kosuge, T}, title = {Prognostic impact of postoperative serum CA 19-9 levels in patients with resectable pancreatic cancer.}, journal = {Annals of surgical oncology}, volume = {19}, number = {2}, pages = {636-641}, doi = {10.1245/s10434-011-2020-9}, pmid = {21863360}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; CA-19-9 Antigen/*blood ; Carcinoma, Pancreatic Ductal/*blood/mortality/surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*blood/mortality/surgery ; Neoplasm Staging ; Pancreatic Neoplasms/*blood/mortality/surgery ; Postoperative Care ; Preoperative Care ; Prognosis ; Prospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Perioperative serum carbohydrate antigen 19-9 (CA 19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The object of this study was to investigate the predictive factors for survival, including preoperative and postoperative serum CA 19-9 levels in patients with pancreatic cancer.

METHODS: Between 2003 and 2009, a total of 269 patients with pancreatic invasive ductal carcinoma underwent macroscopically curative resection, and pre- and postoperative (within 3 months after surgery) serum CA 19-9 levels were evaluated in all of them. The prognostic significance of clinicopathologic factors was evaluated by univariate and multivariate analyses.

RESULTS: Preoperative serum CA 19-9 levels were higher than normal (>37 U/ml, 38-4600 U/ml) in 218 of 269 patients. Of these, after surgery, serum CA 19-9 level returned to within a normal range in 136 patients (62%), whereas 82 patients (38%) remained in the higher-than-normal range. In univariate and multivariate analyses, node metastasis (P < 0.001) and postoperative CA 19-9 level (>37 U/ml) (P < 0.0001) were independent predictors for poor survival. Postoperative CA 19-9 level was higher in patients with microscopically positive surgical margin (P = 0.02). Hepatic recurrence and peritoneal dissemination were associated with postoperative higher CA 19-9 level.

CONCLUSIONS: Postoperative CA 19-9 level was associated with positive surgical margin and hepatic or peritoneal recurrence and may be a useful predictor for survival in patients with pancreatic cancer.}, } @article {pmid21862942, year = {2011}, author = {Usmani, S and Khan, HA and Al Saleh, N and abu Huda, F and Marafi, F and Amanguno, HG and Al Nafisi, N and Al Kandari, F}, title = {Selective approach to radionuclide-guided sentinel lymph node biopsy in high-risk ductal carcinoma in situ of the breast.}, journal = {Nuclear medicine communications}, volume = {32}, number = {11}, pages = {1084-1087}, doi = {10.1097/MNM.0b013e328349eafc}, pmid = {21862942}, issn = {1473-5628}, mesh = {Adult ; Aged ; Axilla/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/*secondary/surgery ; Female ; Humans ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis ; Lymphoscintigraphy/*methods ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging ; Radiopharmaceuticals ; Sentinel Lymph Node Biopsy/*methods ; Technetium Tc 99m Aggregated Albumin ; }, abstract = {PURPOSE: Ductal carcinoma in situ (DCIS) currently represents approximately 15-25% of all breast cancers detected. Although inherently a noninvasive disease, occult invasive disease can be found at definitive histology. The role of sentinel lymph node (SLN) biopsy in DCIS is still unclear. The aim of this study was to evaluate the clinical usefulness of SLN biopsy and the incidence of SLN metastases in selected patients with high-risk DCIS, who are at highest risk for being upstaged to invasive carcinoma.

MATERIALS AND METHODS: Twenty-three high-risk patients with DCIS proven on core biopsy (mean age, 50 years; median age, 48 years; age range, 37-78 years) were included in the study. SLN scintigraphy was performed 2-4 h before surgery by injecting Tc-99m-labeled nanocolloid intradermally in the periareolar region. The first lymph node to appear on the scan was labeled as SLN and was marked on the skin by using a γ probe. The lymph node was explored in the axilla using a γ probe.

RESULTS: The SLN was identified in all patients (100% success rate). Of 23 cases of DCIS on core biopsy, seven patients (30%) were shown to have invasive ductal carcinoma on final histological specimen. Among these seven patients, three had minimal invasive carcinoma (<1 cm) and none of these patients had positive SLN for metastases. Among 23 cases, only one patient with (4%) SLN was positive for metastasis despite histopathological diagnosis of pure DCIS.

CONCLUSION: Although the study population is small, our findings suggest that patients with high-risk DCIS have an increased risk of invasive disease, as approximately one-third of these patients had invasive component at the time of definitive operative procedure. Furthermore, the study also suggests that SLNB appears to be reliable in identifying axillary lymph nodes status of these patients.}, } @article {pmid21860079, year = {2011}, author = {Bhooshan, N and Giger, M and Edwards, D and Yuan, Y and Jansen, S and Li, H and Lan, L and Sattar, H and Newstead, G}, title = {Computerized three-class classification of MRI-based prognostic markers for breast cancer.}, journal = {Physics in medicine and biology}, volume = {56}, number = {18}, pages = {5995-6008}, pmid = {21860079}, issn = {1361-6560}, support = {P50 CA125183/CA/NCI NIH HHS/United States ; P50-CA125183/CA/NCI NIH HHS/United States ; P30 CA14599/CA/NCI NIH HHS/United States ; P30 CA014599/CA/NCI NIH HHS/United States ; R21 CA113800/CA/NCI NIH HHS/United States ; R21 CA113800-01A1/CA/NCI NIH HHS/United States ; S10 RR021039/RR/NCRR NIH HHS/United States ; }, mesh = {Breast Neoplasms/diagnostic imaging/*pathology/therapy ; Female ; Humans ; Magnetic Resonance Imaging/classification/instrumentation/*methods ; Neoplasm Grading/instrumentation/methods ; Pattern Recognition, Automated/methods ; ROC Curve ; Radiographic Image Interpretation, Computer-Assisted/instrumentation/*methods ; Radionuclide Imaging ; }, abstract = {The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks-grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.}, } @article {pmid21854742, year = {2011}, author = {Mazzanti, CM and Al Hamad, M and Fanelli, G and Scatena, C and Zammarchi, F and Zavaglia, K and Lessi, F and Pistello, M and Naccarato, AG and Bevilacqua, G}, title = {A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma.}, journal = {The American journal of pathology}, volume = {179}, number = {4}, pages = {2083-2090}, pmid = {21854742}, issn = {1525-2191}, mesh = {Base Sequence ; Breast Neoplasms/*pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/virology ; *Disease Progression ; Epithelial Cells/pathology ; Female ; Genes, env/*genetics ; Humans ; In Situ Hybridization ; Lasers ; Mammary Tumor Virus, Mouse/*genetics ; Microdissection ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Viral Load ; }, abstract = {A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic tissue, thyroid and colon carcinoma, and blood samples from healthy donors. MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of nine patients were analyzed by real-time quantitative PCR, revealing a different viral load correlated with stage of progression. Furthermore, as never previously described, the presence of MMTVels was investigated by chromogenic in situ hybridization. MMTVels were found in 19% of normal epithelial cells collateral to a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were found in the control samples. Quantitative PCR and chromogenic in situ hybridization confirmed these results. These data could contribute to our understanding of the role of MMTVels in HBC.}, } @article {pmid21853149, year = {2011}, author = {Tjomsland, V and Ellegård, R and Che, K and Hinkula, J and Lifson, JD and Larsson, M}, title = {Complement opsonization of HIV-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families.}, journal = {PloS one}, volume = {6}, number = {8}, pages = {e23542}, pmid = {21853149}, issn = {1932-6203}, support = {AI52731/AI/NIAID NIH HHS/United States ; R01 AI052731/AI/NIAID NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; R37 AI052731/AI/NIAID NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {CD4 Antigens/metabolism ; Cell Differentiation/immunology ; Complement System Proteins/*immunology ; Dendritic Cells/*cytology/immunology/virology ; Endocytosis/immunology ; HIV-1/*immunology ; Humans ; Integrins/*metabolism ; Kinetics ; Lectins, C-Type/*metabolism ; Opsonin Proteins/*immunology ; Receptors, Cell Surface/*metabolism ; Virion/immunology ; Virus Internalization ; }, abstract = {Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.}, } @article {pmid21850995, year = {2011}, author = {Sułko, J}, title = {[Intervertebral disc calcification in children].}, journal = {Chirurgia narzadow ruchu i ortopedia polska}, volume = {76}, number = {1}, pages = {31-35}, pmid = {21850995}, mesh = {Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Calcinosis/complications/*diagnosis/*therapy ; Child ; Child, Preschool ; Female ; Humans ; Intervertebral Disc/*physiopathology ; Male ; Rest ; Retrospective Studies ; Spinal Diseases/complications/*diagnosis/*therapy ; Spine/*physiopathology ; Treatment Outcome ; }, abstract = {THE AIM: Evaluation of children with intervertebral disc calcification (IDC) and own experience.

MATERIALS AND METHODS: A retrospective analysis of 7 patients (2 girls and 5 boys) with detected, in the years 1990-2009, IDC. Age at the onset of symptoms (neck pain in 6 patients, torticollis in 4, hip pain in one) was on average 8.7 years (5-13 years). The diagnosis was based on review of radiographs of the spine, which revealed the presence of calcifications within the intervertebral discs in the cervical (4 patients), cervical and thoracic (2 patients) and thoracic spine (1 patient). The mean level of IDC on average was 3.3 spaces (1-6).

RESULTS: After conservative treatment, including use of nonsteroidal anti-inflammatory drugs and rest, the symptoms subsided within 1-2 weeks. 4 patients had a return of pain in the neck, in one year, but the symptoms were milder and resolved within a few days. The mean observation period was 9 years (3.5-16 years). In 4 patients, changes disappeared completely, while in the remaining three there was a very discrete calcifications. One patient, after 6 years, had a pain in the neck, and CT showed minor lytic changes on the surface of the vertebral bodies between which calcification occurred.

DISCUSSION: ś IDC is a rare disease of the spine in children, but should be taken into account in cases of vertebral pain. Usually the disease affects children before the age of 10 and locates in the cervical spine. But it can be located in every segment of the spine. Most patients have multilevel location. Acute phase of the disease requires conservative treatment. Rarely used surgical treatment should be considered only in patients with persistant neurological symptoms. The natural course of the disease is mild, and over the years calcification gradually disappear spontaneously.}, } @article {pmid21847697, year = {2011}, author = {de Alcantara Filho, P and Capko, D and Barry, JM and Morrow, M and Pusic, A and Sacchini, VS}, title = {Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience.}, journal = {Annals of surgical oncology}, volume = {18}, number = {11}, pages = {3117-3122}, doi = {10.1245/s10434-011-1974-y}, pmid = {21847697}, issn = {1534-4681}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/psychology/*surgery ; Carcinoma, Ductal, Breast/pathology/psychology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Cohort Studies ; Female ; Humans ; *Mastectomy ; Middle Aged ; Nipples/*pathology/surgery ; Prognosis ; Prospective Studies ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. Initially, questions concerning its oncologic safety limited the use of NSM. Nevertheless, mounting evidence supporting the practice of NSM for both prophylactic and oncologic purposes is leading to its more widespread use and broadened indications.

METHODS: Using a prospectively maintained database, we reviewed our experience of 353 NSM procedures performed in 200 patients over the past 10 years.

RESULTS: The indications for surgery were: 196 prophylactic risk-reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who were found to have cancer at the nipple margin, warranting further excision. A total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but only 12 (3.3%) required operative debridement, of which 3 breasts (1%) necessitated removal of a breast implant. Also, 6 patients (2%) were treated for infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No other recurrences are attributable to the 353 NSMs.

CONCLUSIONS: The trends demonstrate the increasing acceptance of NSM as a prophylactic procedure as well as for therapeutic purposes. Although NSM is not standard, our experience supports the selective use of NSM in both prophylactic and malignant settings.}, } @article {pmid21843942, year = {2011}, author = {Meyerson, AF and Lessing, JN and Itakura, K and Hylton, NM and Wolverton, DE and Joe, BN and Esserman, LJ and Hwang, ES}, title = {Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ.}, journal = {Breast (Edinburgh, Scotland)}, volume = {20}, number = {6}, pages = {529-533}, pmid = {21843942}, issn = {1532-3080}, support = {R01 CA069587/CA/NCI NIH HHS/United States ; R01 CA116182/CA/NCI NIH HHS/United States ; K23 CA0977181/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*therapy ; Cohort Studies ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Receptors, Estrogen/*metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {INTRODUCTION: An option for active surveillance is not currently offered to patients with ductal carcinoma in situ (DCIS); however a small number of women decline standard surgical treatment for noninvasive cancer. The purpose of this study was to assess outcomes in a cohort of 14 well-informed women who elected non-surgical active surveillance with endocrine treatment alone for estrogen receptor-positive DCIS.

METHODS: Retrospective review of 14 women, 12 of whom were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant endocrine therapy prior to definitive surgical management. The patients in this report withdrew from the parent study opting instead for active surveillance with endocrine treatment and imaging.

RESULTS: 8 women had surgery at a median follow up of 28.3 months (range 10.1-70 months), 5 had stage I IDC at surgical excision, and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive disease for a median of 31.8 months (range 11.8-80.8 months).

CONCLUSION: Long-term active surveillance for DCIS is feasible in a well-informed patient population, but is associated with risk of invasive cancer at surgical excision.}, } @article {pmid21840784, year = {2011}, author = {Almeida, M and Muñoz, J and Nunes, S and Fonseca-Moutinho, J}, title = {Cyclooxygenase-2 immunoexpression in breast cancer: progesterone receptor influence.}, journal = {Cancer epidemiology}, volume = {35}, number = {6}, pages = {e81-4}, doi = {10.1016/j.canep.2011.05.007}, pmid = {21840784}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cyclooxygenase 2/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptors, Progesterone/*biosynthesis ; }, abstract = {BACKGROUND: In breast cancer cyclooxygenase-2 overexpression is related with poor outcomes, but the clinical relevance of cyclooxygenase-2 is still unclear. Progesterone receptor is a regulator of cyclooxygenase-2 expression. We postulate that progesterone receptor was associated to cyclooxygenase-2 expression and clinicopathologic factors in breast cancer.

METHODS: Cyclooxygenase-2 and progesterone receptor expression was analyzed, by immunohistochemistry, in 31 cases of invasive ductal carcinoma.

RESULTS: The expression of cyclooxygenase-2 and progesterone receptor was observed in 64.5% and 45.2% of the tumors, respectively. We found 11 tumors with both cyclooxygenase-2 and progesterone receptor overexpression and they are related with tumor lower size and lower axillary node metastasis.

CONCLUSION: These results suggest that progesterone receptor has a protective role in breast cancer by inhibiting chronic inflammatory pathway.}, } @article {pmid21837405, year = {2011}, author = {Yokoyama, Y and Nagino, M}, title = {Role of extended surgery for pancreatic cancer: critical review of the four major RCTs comparing standard and extended surgery.}, journal = {Journal of hepato-biliary-pancreatic sciences}, volume = {18}, number = {6}, pages = {785-791}, doi = {10.1007/s00534-011-0432-3}, pmid = {21837405}, issn = {1868-6982}, mesh = {Humans ; Pancreatectomy/*methods ; Pancreatic Neoplasms/*surgery ; Pancreaticoduodenectomy/*methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Pancreatic ductal carcinoma is one of the most dismal malignancies in the gastrointestinal system. Despite the development of several adjuvant therapeutic options, surgical treatment is still the only procedure that can completely cure this disease. Since pancreatic cancer easily extends to the adjacent tissues or develops distant metastasis, there has been argument as to whether we should perform extended surgery in order to widely eradicate peripancreatic tissue. After the report from Japanese surgeons that showed a survival benefit of the extended surgery for the invasive ductal carcinoma of the pancreas in the late 1980s, many Japanese surgeons applied the extended surgery for pancreatic cancer. However, the major problems of these studies were the retrospective and non-randomized nature of the study design. Thereafter, randomized controlled trials (RCT) comparing a standard and extended resection for the pancreatic cancer have been conducted first in Europe, second and third in the USA, and, subsequently, fourth in Japan. Unexpectedly, the survival benefit of the aggressive surgery has been refuted in all of the four major RCTs. This fact implied to us that surgery alone is not enough and that another adjuvant therapeutic option is necessary in order to improve the patients' survival of pancreatic cancer.}, } @article {pmid21833355, year = {2011}, author = {Yang, Y and Li, F and Gao, L and Wang, Z and Thrall, MJ and Shen, SS and Wong, KK and Wong, ST}, title = {Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging.}, journal = {Biomedical optics express}, volume = {2}, number = {8}, pages = {2160-2174}, pmid = {21833355}, issn = {2156-7085}, abstract = {We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.}, } @article {pmid21827679, year = {2011}, author = {Gomes, DS and Balabram, D and Porto, SS and Gobbi, H}, title = {Lobular neoplasia: frequency and association with other breast lesions.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {74}, pmid = {21827679}, issn = {1746-1596}, mesh = {Aged ; Analysis of Variance ; Biopsy ; Brazil/epidemiology ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma in Situ/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/*pathology ; Carcinoma, Lobular/epidemiology/*pathology ; Chi-Square Distribution ; Female ; Humans ; Hyperplasia ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {BACKGROUND: Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions.

METHODS: Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008). Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend.

RESULTS: We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4%) that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%). Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2%) as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p < 0.03) of a higher frequency of invasive carcinomas that were concomitant with lobular carcinoma in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular hyperplasia cases.

CONCLUSIONS: Our findings confirm a frequent association between lobular neoplasia and columnar cell lesions, the majority of which lacked atypia. We also observed a greater frequency of invasive carcinoma, more commonly invasive lobular carcinoma, associated with more developed forms of lobular neoplasia (lobular carcinoma in situ).}, } @article {pmid21820646, year = {2011}, author = {Shahar, B and Herr, NR}, title = {Depressive symptoms predict inflexibly high levels of experiential avoidance in response to daily negative affect: a daily diary study.}, journal = {Behaviour research and therapy}, volume = {49}, number = {10}, pages = {676-681}, doi = {10.1016/j.brat.2011.07.006}, pmid = {21820646}, issn = {1873-622X}, mesh = {Adaptation, Psychological ; Adolescent ; *Affect ; Avoidance Learning ; *Defense Mechanisms ; Depression/*psychology ; Female ; Humans ; Male ; Psychometrics/*instrumentation/methods ; Records ; Reference Values ; Self-Assessment ; Social Environment ; Young Adult ; }, abstract = {Experiential avoidance (EA) is an emotion-regulation strategy used to control or avoid unpleasant internal experiences. Despite the important role of avoidance in depressive disorders, there is relatively little research directly examining the role of EA in the development and maintenance of depression, and most of this research relies on measurement of EA as a global and stable personality trait. In this study we sought to extend the research on EA and depression by using a daily diary design and multilevel analysis to examine how the daily relationship between EA and negative affect (NA) varies as a function of baseline depressive symptoms. In order to achieve this goal we created a new state measure of EA assessing several avoidant behaviors. The findings revealed that participants with more depressive symptoms used more daily EA overall. Additionally, the difference in daily EA between those with higher versus lower depressive symptoms was greater on days when participants experienced less NA. This moderation effect was found only concurrently whereas one-day lagged analysis failed to reveal this effect. These findings provide preliminary support for the hypothesis that depression is associated with an inflexibly high level of avoidant emotion regulation.}, } @article {pmid21811891, year = {2011}, author = {Dragu, A and Hohenberger, W and Lang, W and Schmidt, J and Horch, RE}, title = {[Forequarter amputation of the right upper chest: limitations of ultra radical interdisciplinary oncological surgery].}, journal = {Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen}, volume = {82}, number = {9}, pages = {834-838}, pmid = {21811891}, issn = {1433-0385}, mesh = {Amputation, Surgical/*methods ; Blood Loss, Surgical/physiopathology ; Brachial Plexus/pathology/surgery ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal/pathology/*surgery ; Chemoradiotherapy, Adjuvant ; Combined Modality Therapy ; *Cooperative Behavior ; Fatal Outcome ; Female ; Fibrosarcoma/pathology/*surgery ; Free Tissue Flaps/*blood supply ; Humans ; *Interdisciplinary Communication ; Lymphatic Metastasis/pathology ; Microsurgery/methods ; Middle Aged ; Multiple Organ Failure/etiology/therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplasms, Second Primary/pathology/*surgery ; *Patient Care Team ; Postoperative Complications/*etiology/therapy ; Sternum/*surgery ; Surgical Flaps ; Surgical Mesh ; Thoracic Neoplasms/pathology/*surgery ; Thoracic Wall/*surgery ; }, abstract = {Total forearm free flap procedures after forequarter amputations have been sparsely described in the literature. Using the amputated arm as a "free filet flap" remains a viable surgical option after radical forequarter amputations performed for the resection of large, invasive tumors of the shoulder or thoracic wall region. Using the forequarter specimen as a donor site seems favorable in that it eliminates the usual donor site morbidity. Nevertheless, in our patient with invasive ductal carcinoma of the breast and a fibrosarcoma suffering from severe pain and septic conditions - which failed to respond properly to conservative therapy - as well as rapidly progressive tumor ulceration despite repeated radiation therapy, we decided to attempt complete tumor removal by hemithoracectomy as a last resort. This decision was taken following multiple interdisciplinary consultations and thorough patient information. Although technically feasible with complete tumor removal and safe soft tissue free flap coverage, the postoperative course raises questions about the advisability of such ultra radical surgical procedures, as well as about the limitations of respiratory recovery after hemithoracectomy with removal of the sternum. Hence, based on our experience with such radical tumor surgery, we discuss the issues of diminished postoperative pulmonary function, intensive care possibilities and ethical issues. The English full-text version of this article is available at SpringerLink (under "Supplemental").}, } @article {pmid21811256, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Modified primary tumour/vessel tumour/nodal tumour classification for patients with invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {105}, number = {5}, pages = {698-708}, pmid = {21811256}, issn = {1532-1827}, mesh = {Adult ; Aged ; Breast Neoplasms/*classification/diagnosis/mortality/pathology ; Carcinoma, Ductal, Breast/*classification/diagnosis/mortality/pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging/*methods ; Neoplasms, Vascular Tissue/*classification/diagnosis/mortality/secondary ; Prognosis ; Recurrence ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status.

METHODS: The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model.

RESULTS: The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status.

CONCLUSION: The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.}, } @article {pmid21810278, year = {2011}, author = {Mok, S and Imwong, M and Mackinnon, MJ and Sim, J and Ramadoss, R and Yi, P and Mayxay, M and Chotivanich, K and Liong, KY and Russell, B and Socheat, D and Newton, PN and Day, NP and White, NJ and Preiser, PR and Nosten, F and Dondorp, AM and Bozdech, Z}, title = {Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription.}, journal = {BMC genomics}, volume = {12}, number = {}, pages = {391}, pmid = {21810278}, issn = {1471-2164}, support = {093956//Wellcome Trust/United Kingdom ; }, mesh = {Antimalarials/*pharmacology ; Artemisinins/*pharmacology ; DNA Copy Number Variations/drug effects/genetics ; Drug Resistance/*genetics ; *Gene Expression Profiling ; Genomics ; Genotype ; Humans ; Plasmodium falciparum/cytology/*drug effects/*genetics/metabolism ; Protozoan Proteins/biosynthesis/genetics/metabolism ; Time Factors ; Transcription, Genetic/*drug effects ; Trophozoites/cytology/drug effects/metabolism ; }, abstract = {BACKGROUND: Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates.

RESULTS: In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype.

CONCLUSIONS: The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo.}, } @article {pmid21802218, year = {2011}, author = {Wang, Z and Shi, Q and Wang, Z and Gu, Y and Shen, Y and Sun, M and Deng, M and Zhang, H and Fang, J and Zhang, S and Xie, F}, title = {Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.}, journal = {Pathology, research and practice}, volume = {207}, number = {8}, pages = {505-513}, doi = {10.1016/j.prp.2011.06.009}, pmid = {21802218}, issn = {1618-0631}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/metabolism ; Breast Neoplasms/*metabolism/pathology ; CD24 Antigen/biosynthesis ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Hyaluronan Receptors/biosynthesis ; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis ; Immunohistochemistry ; Middle Aged ; Neoplastic Stem Cells/*metabolism/pathology ; Pilot Projects ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {CD24(-/low)CD44(+) cells have been identified as putative cancer stem cells (CSCs) in breast cancer. However, the expression of these markers, as well as their association with clinical parameters or tumor microenvironment of breast cancer, remains largely unknown. In the present study, we examined the expression of CD44, CD24, VEGF, and HIF-1α in human breast tumor tissues and assessed their clinicopathological correlations. We investigated tissue samples, including 117 cases of invasive ductal carcinoma (IDCa), 14 cases of ductal carcinoma in situ (DCIS), and 15 cases of intraductal hyperplasia (IDH) from breast tissues. The expression of CD44, CD24, HIF-1α, and VEGF was evaluated using immunohistochemical staining. CD24, CD44, HIF-1α, and VEGF were expressed in 49 (41.9%), 51 (43.6%), 32 (27.4%), and 97 cases (82.9%), respectively, in IDCa. CD24(-/low)CD44(+) cells were noted in 48 (41.3%) cases. The levels of CD24 and VEGF expression correlated positively with tumor malignancy (P<0.05). Meanwhile, the expression of CD24, CD44, and VEGF correlated significantly positively with increasing tumor grade (P<0.05). In addition, associations between CD44 and VEGF, CD24 and VEGF, HIF-1α and VEGF, CD24(-/low)CD44(+) and VEGF, CD24(-/low)CD44(+) and HIF-1α were also observed (P<0.05). The HIF-1α expression level was relatively higher in early stage breast cancer patients with CD24(-/low)CD44(+) cells. Taken together, our results suggest that CD24 and VEGF may play important roles in breast tumorigenesis and progression, while HIF-1α may play a role in the early stage of breast carcinogenesis.}, } @article {pmid21793875, year = {2011}, author = {Klomek, AB and Kleinman, M and Altschuler, E and Marrocco, F and Amakawa, L and Gould, MS}, title = {High school bullying as a risk for later depression and suicidality.}, journal = {Suicide & life-threatening behavior}, volume = {41}, number = {5}, pages = {501-516}, pmid = {21793875}, issn = {1943-278X}, support = {R01 MH064632/MH/NIMH NIH HHS/United States ; R01 MH064632-01/MH/NIMH NIH HHS/United States ; R49 CE000258/CE/NCIPC CDC HHS/United States ; R01-MH64632/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bullying/*psychology ; Cross-Sectional Studies ; Depression/diagnosis/*psychology ; Depressive Disorder/diagnosis/*psychology ; Female ; Humans ; Longitudinal Studies ; Male ; Risk Factors ; Schools ; Students/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; }, abstract = {This is the first study to examine whether high school students experiencing frequent bullying behaviors are at risk for later depression and suicidality. A total of 236 students who reported frequent bullying behavior without depression or suicidality during a suicide screening were interviewed 4 years later to reassess depression, suicidal ideation, attempts, substance problems, and functional impairment and were compared to at-risk youth identified during the screen, including 96 youth who also experienced bullying behavior. Youth who only reported frequent bullying behaviors (as bullies, victims, or both) did not develop later depression or suicidality and continued to have fewer psychiatric problems than students identified as at-risk for suicide. Students who experienced bullying behaviors and depression or suicidality were more impaired 4 years later than those who had only reported depression or suicidality. Thus, assessment of bullying behaviors in screening protocols is recommended.}, } @article {pmid21791203, year = {2011}, author = {Tuszynski, GP and Rothman, VL and Zheng, X and Gutu, M and Zhang, X and Chang, F}, title = {G-protein coupled receptor-associated sorting protein 1 (GASP-1), a potential biomarker in breast cancer.}, journal = {Experimental and molecular pathology}, volume = {91}, number = {2}, pages = {608-613}, doi = {10.1016/j.yexmp.2011.06.015}, pmid = {21791203}, issn = {1096-0945}, mesh = {Amino Acid Sequence ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Electrophoresis ; Female ; Humans ; Hydrophobic and Hydrophilic Interactions ; Immunohistochemistry ; Molecular Sequence Data ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Peptides/chemistry/metabolism ; Protein Binding ; Serum Albumin ; Vesicular Transport Proteins/chemistry/*metabolism ; }, abstract = {An innovative "2-D high performance liquid electrophoresis" (2-D HPLE) technology was used to identify serum biomarkers associated with the early stage of breast cancer in addition to other more advanced stages. 2-D HPLE is a newly developed electrophoretic technology that separates 100s of serum albumin complexes on a polyvinyl membrane based on their surface charges. Association of cancer proteins or their fragments (biomarkers) with pre-existing albumin complexes in the blood of cancer patients results in altered mobility on the membrane. Using 2-D HPLE we identified that a specific fragment of G-protein coupled receptor-associated sorting protein 1 (GASP-1) was present in the sera of patients with early stage disease but absent in sera of normal patients. GASP-1 has been shown to modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors in neuronal cells. However, no reports have linked GASP-1 to breast cancer pathogenesis. GASP-1 was detected in tumor extracts of 7 cases of Stage 2 and Stage 3 breast cancers, but not in adjacent normal tissue as revealed by western blot analysis using an antibody developed against a GASP-1 peptide identified by our 2-D HPLE technology. Using this antibody, we immunohistochemically detected over-expression of GASP-1 in all of 107 cases of archived ductal breast carcinoma tumor samples, while normal adjacent breast tissue from 12 cases of ductal carcinoma showed little or no staining. Additionally, all 10 cases of metastatic breast carcinoma present in lymph nodes were positive. Strong positive GASP-1 staining was observed in all tumor tissue including ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. Additionally, we observed a wide spectrum of enhanced staining of premalignant ductal epithelial cells present in benign ducts and those found in atypical ductal hyperplasia (ADH). These studies identify GASP-1 as a potential new serum and tumor biomarker for breast cancer and suggest that GASP-1 may be a novel target for the development of breast cancer therapeutics.}, } @article {pmid21790824, year = {2011}, author = {van Balkom, ID and Shaw, A and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism.}, journal = {Journal of intellectual disability research : JIDR}, volume = {55}, number = {10}, pages = {973-987}, doi = {10.1111/j.1365-2788.2011.01451.x}, pmid = {21790824}, issn = {1365-2788}, mesh = {Abnormalities, Multiple/*diagnosis/*genetics/psychology ; Adaptation, Psychological ; Adolescent ; Autistic Disorder/*diagnosis/*genetics/psychology ; Bone Diseases, Developmental/*diagnosis/*genetics/psychology ; Child ; Child Behavior Disorders/*diagnosis/*genetics/psychology ; Child, Preschool ; Communication ; Craniofacial Abnormalities/*diagnosis/*genetics/psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Female ; Humans ; Intellectual Disability/*diagnosis/*genetics/psychology ; Male ; NFI Transcription Factors/genetics ; Neurologic Examination ; Neuropsychological Tests ; Personality Assessment ; *Phenotype ; Prognosis ; Septo-Optic Dysplasia/*diagnosis/*genetics/psychology ; }, abstract = {BACKGROUND: Marshall-Smith syndrome (MSS) is an infrequently described entity characterised by failure to thrive, developmental delay, abnormal bone maturation and a characteristic face. In studying the physical features of a group of patients, we noticed unusual behavioural traits. This urged us to study cognition, behavioural phenotype and autism in six patients.

METHODS: Information on development, behavioural characteristics, autism symptoms, and adaptive and psychological functioning of six MSS children was collected through in-person examinations, questionnaires, semi-structured interviews of parents and neuropsychological assessments.

RESULTS: Participants showed moderate to severe delays in mental age, motor development and adaptive functioning, with several similarities in communication, social interactions and behaviour. There was severe delay of speech and motor milestones, a friendly or happy demeanour and enjoyment of social interactions with familiar others. They exhibited minimal maladaptive behaviours. Deficits in communication and social interactions, lack of reciprocal social communication skills, limited imaginary play and the occurrence of stereotyped, repetitive behaviours were noted during assessments.

CONCLUSIONS: Systematic collection of developmental and behavioural data in very rare entities such as MSS allows recognition of specific patterns in these qualities. Clinical recognition of physical,developmental and behavioural features is important not only for diagnosis, prognosis and counselling of families, but also increases our understanding of the biological basis of the human physical and behavioural phenotype.}, } @article {pmid21789264, year = {2011}, author = {Bukhari, MH and Arshad, M and Jamal, S and Niazi, S and Bashir, S and Bakhshi, IM and Shaharyar, }, title = {Use of fine-needle aspiration in the evaluation of breast lumps.}, journal = {Pathology research international}, volume = {2011}, number = {}, pages = {689521}, pmid = {21789264}, issn = {2042-003X}, abstract = {Background. A study was designed to see the role of fine needle aspiration cytology (FNAC) in palpable breast lumps. Materials and Methods. Four hundred and twenty five (425) patients came to the Department of Pathology King Edward Medical University, Lahore in four years for FNAC of their palpable breast masses from June 2006 to June 2010. FNAC diagnosis was compared with histological diagnosis to see the accuracy of fine needle aspiration cytology for neoplastic lesions. Results. There were 271/425 benign, 120/425 malignant, and 32/425 suspicious smears. Inadequate samples were repeated twice or thrice, and the degree of success was improved with consecutive repeating approaches. The frequency of inadequacy declined from 86 to 18, and 2 for first, second and third attempts, respectively. The number of repeats increased the diagnostic accuracy of aspirates which is statistically significant (P = .000). Invasive ductal carcinoma was the most commonly reported lesion with maximum incidence in the 4th, 5th, and 6th decades followed by invasive lobular carcinoma and other malignant lesions. The sensitivity, specificity, accuracy, negative predictive value, and the positive predictive value of FNAC was 98%, 100%, 98%, 100%, and 97%, respectively. Conclusion. FNAC serves as a rapid, economical, and reliable tool for the diagnosis of palpable breast lesions because the cytopathological examination of these lesions before operation or treatment serves as an important diagnostic modality.}, } @article {pmid21789023, year = {2011}, author = {Ma, L and Liu, YP and Geng, CZ and Xing, LX and Zhang, XH}, title = {Low-dose epirubicin inhibits ezrin-mediated metastatic behavior of breast cancer cells.}, journal = {Tumori}, volume = {97}, number = {3}, pages = {400-405}, doi = {10.1177/030089161109700324}, pmid = {21789023}, issn = {0300-8916}, mesh = {Adult ; Aged ; Antibiotics, Antineoplastic/*pharmacology ; Blotting, Western ; Breast Neoplasms/*drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/*pathology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cytoskeletal Proteins/*metabolism ; Disease Progression ; Epirubicin/*pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation ; }, abstract = {AIMS AND BACKGROUND: Overexpression of ezrin contributes to the progression and invasiveness of several human cancers; however, its role in breast cancer metastasis has not been investigated in detail.

METHODS: Ezrin expression in tissue samples from patients with invasive ductal carcinoma of the breast was detected by immunohistochemistry. Ezrin expression in a breast cancer cell line was evaluated using Western blot and RT-PCR.

RESULTS: Elevated expression of ezrin was associated with lymph node metastasis and poor prognosis in patients with invasive ductal carcinoma. Ezrin expression was related to the invasiveness of breast cancer cells in vitro. Low-dose epirubicin inhibited the migration of breast cancer cells in a concentration-dependent manner without promoting cytotoxicity in vitro and decreased the expression of ezrin in a concentration-dependent manner.

CONCLUSIONS: Low-dose epirubicin may be antimetastatic without promoting cytotoxic effects and could serve as a target for the development of therapeutics for breast carcinoma.}, } @article {pmid21785902, year = {2012}, author = {Kandemir, NO and Barut, F and Bektas, S and Ozdamar, SO}, title = {Can lymphatic vascular density be used in determining metastatic spreading potential of tumor in invasive ductal carcinomas?.}, journal = {Pathology oncology research : POR}, volume = {18}, number = {2}, pages = {253-262}, pmid = {21785902}, issn = {1532-2807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/metabolism ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Node Excision ; *Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels/*pathology ; Mastectomy ; Middle Aged ; *Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Retrospective Studies ; }, abstract = {Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p < 0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p > 0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&E] (p = 0.04), number of lymphatic invasion [n/mm2, D2-40] (p = 0.001), tumor size (p = 0.01), lymph node status (p = 0.03), and tumor stage (p = 0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor's biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.}, } @article {pmid21785684, year = {2011}, author = {Nasir, A and Chen, DT and Gruidl, M and Henderson-Jackson, EB and Venkataramu, C and McCarthy, SM and McBride, HL and Harris, E and Khakpour, N and Yeatman, TJ}, title = {Novel molecular markers of malignancy in histologically normal and benign breast.}, journal = {Pathology research international}, volume = {2011}, number = {}, pages = {489064}, pmid = {21785684}, issn = {2042-003X}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA098522/CA/NCI NIH HHS/United States ; }, abstract = {To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and "budding-uninhibited-by-benzimidazoles-1-homolog-beta" (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; N = 9) and high-grade molecular abnormality (HNB-HGMA; N = 9). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0-300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.}, } @article {pmid21782124, year = {2011}, author = {Le-Petross, H and Lane, D}, title = {Challenges and potential pitfalls in magnetic resonance imaging of more elusive breast carcinomas.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {32}, number = {4}, pages = {342-350}, doi = {10.1053/j.sult.2011.03.004}, pmid = {21782124}, issn = {0887-2171}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Inflammatory Breast Neoplasms/pathology ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {Breast cancer is a heterogeneous group of diseases caused by differences in the biological, clinical, radiologic, and pathologic features of the different types of invasive carcinoma in the breast. The majority of invasive breast carcinomas are the invasive ductal or no special-type (NST) carcinomas. The rest of the invasive carcinomas are either nonductal carcinoma subtypes or special-type carcinomas, making up 20%-30% of all invasive carcinomas. The latter group comprises very different and distinctive types of cancer with imaging characteristics and challenges that are unique to each subtype. The invasive lobular carcinoma is the most common type of the nonductal carcinomas and can be difficult to detect on imaging because of the distinct pattern of tumor growth in sheets of single file cells with minimal desmoplastic reaction. The mucinous carcinoma of the breast contains extracellular mucin, secreted by the tumor cells. The mucin within these tumors result in imaging features that overlap with benign breast lesions, and may lead to misdiagnosis. Other rare and aggressive breast cancers include metaplastic breast carcinoma and inflammatory breast carcinoma. Both diseases have a poorer prognosis than invasive ductal carcinoma. This article will focus on the rarer non-NST carcinoma of the breast that can be a challenge to assess with imaging, partially related to the unique biology of these cancers.}, } @article {pmid21780520, year = {2011}, author = {Dubowy, A and Raubach, M and Topalidis, T and Lange, T and Eulenstein, S and Hünerbein, M}, title = {Breast duct endoscopy: ductoscopy from a diagnostic to an interventional procedure and its future perspective.}, journal = {Acta chirurgica Belgica}, volume = {111}, number = {3}, pages = {142-145}, doi = {10.1080/00015458.2011.11680725}, pmid = {21780520}, issn = {0001-5458}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/surgery ; Diagnosis, Differential ; Endoscopy/*methods ; Female ; Follow-Up Studies ; Humans ; *Mastectomy ; Middle Aged ; Nipples/*pathology ; Papilloma, Intraductal/*diagnosis/surgery ; Reproducibility of Results ; Young Adult ; }, abstract = {OBJECTIVE: Breast duct endoscopy is increasingly used for evaluation of intraductal disease. We present a new rigid instrument for ductoscopy that allows intraductal biopsy and the removal of small lesions.

METHODS: Overall, 102 women with breast cancer or pathologic nipple discharge were included in the analysis. All ductoscopies were performed with a rigid gradient index micro-endoscope (phi 0.7 mm) in combination with a special device for intraductal vacuum assisted biopsy. Ductoscopy, ductal lavage and intraductal biopsy were correlated with ductal cytology and histopathology of the resection specimen.

RESULTS: Gradient index ductoscopy provided high resolution images of the breast ducts and identified additional intraductal lesions in 45% of the patients with breast cancer. The accuracy of ductal lavage, ductoscopy and mammography in the detection of an extensive intraductal component was 14%, 65% and 50%, respectively. Intraductal vacuum assisted biopsy yielded diagnostic material in 92% of 38 patients with nipple discharge and papillomatous lesions. Histology of the resection specimen confirmed the diagnosis in all cases including 2 in situ carcinoma and 2 invasive ductal carcinoma.

CONCLUSIONS: Ductoscopy is a useful supplement for the standard radiological workup of breast cancer especially in patients with extensive intraductal carcinoma. Ductoscopic vacuum assisted biopsy is an effective technique for intraductal tissue sampling and allows ablation of small lesions. This technique provides new perspectives for interventional therapy of intraductal tumours.}, } @article {pmid21780225, year = {2011}, author = {Mann, RM and Veltman, J and Huisman, H and Boetes, C}, title = {Comparison of enhancement characteristics between invasive lobular carcinoma and invasive ductal carcinoma.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {34}, number = {2}, pages = {293-300}, doi = {10.1002/jmri.22632}, pmid = {21780225}, issn = {1522-2586}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Contrast Media/pharmacokinetics ; Female ; Humans ; Kinetics ; Magnetic Resonance Imaging/*methods ; Medical Oncology/methods ; Middle Aged ; }, abstract = {PURPOSE: To compare enhancement characteristics between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) on contrast enhanced MRI of the breast and to observe the magnitude of eventual differences as these may impair the diagnostic value of breast MRI in ILC.

MATERIALS AND METHODS: We performed an analysis of enhancement characteristics on biphasic breast MRI in a series of 136 patients (103 IDC, 33 ILC) using an in-house developed application for pharmacokinetic modeling of contrast enhancement and a commercially available CAD application that evaluated the contrast-enhancement versus time curve.

RESULTS: Pharmacokinetic analysis showed that the most enhancing voxels in IDC had significantly higher K(trans) -values than in ILC (P < 0.01). No difference in v(e) -values was noted between groups. Visual assessment of contrast-enhancement versus time curves revealed wash-out curves to be less common in ILC (48% versus 84%). However, when using the CAD-application to assess the most malignant looking curve, the difference was blotted out (76% versus 86%).

CONCLUSION: ILC enhances slower than IDC but peak enhancement is not significantly less. The use of a CAD-application may help to determine the most malignant looking contrast-enhancement versus time curve, and hence facilitates lesion classification.}, } @article {pmid21779814, year = {2014}, author = {Koike, K and Kitahara, K and Higaki, M and Urata, M and Yamazaki, F and Noshiro, H}, title = {Clinicopathological features of gastric metastasis from breast cancer in three cases.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {5}, pages = {629-634}, doi = {10.1007/s12282-011-0284-3}, pmid = {21779814}, issn = {1880-4233}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla/pathology/surgery ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Lymph Node Excision ; Middle Aged ; Stomach Neoplasms/drug therapy/*pathology/*secondary ; Treatment Outcome ; }, abstract = {The common sites for metastases from breast cancer are lymph nodes, bone, lung, liver, and brain. Gastrointestinal (GI) metastasis is rarely found or diagnosed in patients with breast cancer. This report presents three cases of gastric metastasis from breast cancer. Case 1 was a 42-year-old female diagnosed with gastric metastasis after mastectomy with axillary lymph node dissection for invasive lobular carcinoma of the left breast. Case 2 was a 54-year-old female who was diagnosed to have invasive lobular carcinoma of the left breast with systemic bone and gastric metastasis. Case 3 was a 54-year-old female who was diagnosed to have bilateral invasive ductal carcinoma of the breast with simultaneous bone and gastric metastasis. The immunohistochemical statuses for estrogen receptor, progesterone receptor, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15) between the primary and gastric metastatic lesions were all well matched. All three cases were treated with systemic chemotherapy, hormone therapy or both, without surgical intervention for gastric lesions. Two patients with disseminated disease died 27 and 58 months after diagnosis of gastric metastasis, while one patient without organ metastasis is still alive at 56 months after diagnosis. It is important to make a correct diagnosis by distinguishing gastric metastasis from breast cancer in order to select the optimal initial treatment for systemic disease of breast cancer.}, } @article {pmid21779467, year = {2010}, author = {Ossovskaya, V and Koo, IC and Kaldjian, EP and Alvares, C and Sherman, BM}, title = {Upregulation of Poly (ADP-Ribose) Polymerase-1 (PARP1) in Triple-Negative Breast Cancer and Other Primary Human Tumor Types.}, journal = {Genes & cancer}, volume = {1}, number = {8}, pages = {812-821}, pmid = {21779467}, issn = {1947-6027}, abstract = {Poly (ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair and is implicated in pathways of tumorigenesis. PARP inhibitors have gained recent attention as rationally designed therapeutics for the treatment of several malignancies, particularly those associated with dysfunctional DNA repair pathways, including triple-negative breast cancer (TNBC). We investigated the PARP1 gene expression profile in surgical samples from more than 8,000 primary malignant and normal human tissues. PARP1 expression was found to be significantly increased in several malignant tissues, including those isolated from patients with breast, uterine, lung, ovarian, and skin cancers, and non-Hodgkin's lymphoma. Within breast infiltrating ductal carcinoma (IDC) samples tested, mean PARP1 expression was significantly higher relative to normal breast tissue, with over 30% of IDC samples demonstrating upregulation of PARP1, compared with 2.9% of normal tissues. Because of known DNA repair defects, including BRCA1 dysfunction, associated with TNBC, exploration of PARP1 expression in breast cancers related to expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) led to the observation that negative expression of any of the 3 receptors was associated with upregulation of PARP1 expression, compared with receptor-positive tissues. To validate these observations, an independent set of breast adenocarcinomas was evaluated and demonstrated >2-fold upregulation of PARP1 in approximately 70% of primary breast adenocarcinomas, including TNBC, compared with syngeneic nonmalignant breast tissues. Immunohistochemistry (IHC) showed that upregulation of the PARP1 gene was consistent with increased protein expression in TNBC. These analyses suggest a potential biological role for PARP1 in several distinct malignancies, including TNBC. Further investigation of PARP1 as a biomarker for the therapeutic activity of PARP inhibitor-based therapy is warranted.}, } @article {pmid21779299, year = {2011}, author = {Sunwoo, MK and Kim, SM and Lee, S and Lee, PH}, title = {Parkinsonism associated with glucocerebrosidase mutation.}, journal = {Journal of clinical neurology (Seoul, Korea)}, volume = {7}, number = {2}, pages = {99-101}, pmid = {21779299}, issn = {2005-5013}, abstract = {BACKGROUND: Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations.

CASE REPORT: A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. (18)F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen.

CONCLUSIONS: This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation.}, } @article {pmid21776434, year = {2011}, author = {Sato, T and Neilson, LM and Peck, AR and Liu, C and Tran, TH and Witkiewicz, A and Hyslop, T and Nevalainen, MT and Sauter, G and Rui, H}, title = {Signal transducer and activator of transcription-3 and breast cancer prognosis.}, journal = {American journal of cancer research}, volume = {1}, number = {3}, pages = {347-355}, pmid = {21776434}, issn = {2156-6976}, support = {R01 CA101841-01A1/CA/NCI NIH HHS/United States ; P30 CA056036/CA/NCI NIH HHS/United States ; R01 CA101841/CA/NCI NIH HHS/United States ; R01 CA118740/CA/NCI NIH HHS/United States ; R01 CA113580/CA/NCI NIH HHS/United States ; R01 CA118740-01A1/CA/NCI NIH HHS/United States ; }, abstract = {Signal transducer and activator of transcription-3 (Stat3) is frequently activated in breast cancer and multiple lines of evidence suggest that Stat3 promotes tumor progression. However, the prognostic value of Stat3 in human breast cancer remains controversial and associations range from favorable to unfavorable based on four outcome studies of 62, 102, 255 and 517 patients. Cellular Stat3 protein expression was measured in three studies whereas nuclear localized, tyrosine phosphorylated Stat3 (Nuc-pYStat3) was used as the readout in only one study. We therefore retrospectively analyzed the prognostic value of Nuc-pYStat3 in a larger material of 721 breast cancer specimens. Overall, patients whose tumors were positive for Nuc-pYStat3 tended to have improved survival, but the trend did not reach statistical significance (P=0.08). When specimens were stratified by tumor grade, patients with low grade but not high grade tumors that were positive for Nuc-pYStat3 had significantly prolonged overall survival in univariate analysis (P=0.014) but not in multivariate analyses. Unexpectedly, quantitative immunofluoresence detection revealed highest levels of Nuc-pYStat3 in normal breast epithelia and gradual loss of Nuc-pYStat3 during progression from DCIS, invasive ductal carcinoma, and lymph node metastases. Levels of Nuc-pYStat3 correlated positively with levels of Nuc-pYStat5, a favorable prognostic marker, in invasive ductal carcinomas. Furthermore, NucpYStat3 levels correlated strongly with protein levels of nuclear localized Stat5a (r=0.633, P<0.001) but not Stat5b. Our data does not support the notion that Nuc-pYStat3 is an independent marker of prognosis in breast cancer, although future studies may reveal prognostic utility within molecularly characterized subtypes of breast cancer.}, } @article {pmid21771800, year = {2011}, author = {Barbosa, MM and Rocha, MO and Botoni, FA and Ribeiro, AL and Nunes, MC}, title = {Is atrial function in Chagas dilated cardiomyopathy more impaired than in idiopathic dilated cardiomyopathy?.}, journal = {European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology}, volume = {12}, number = {9}, pages = {643-647}, doi = {10.1093/ejechocard/jer096}, pmid = {21771800}, issn = {1532-2114}, mesh = {Adult ; *Atrial Function ; Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology ; Chagas Cardiomyopathy/diagnostic imaging/*physiopathology ; Echocardiography, Doppler, Pulsed ; Female ; Humans ; Male ; Ventricular Function ; }, abstract = {AIMS: Atrial function is an important component in overall cardiovascular performance. However, information on atrial function in dilated cardiomyopathy is limited. This study aimed to assess atrial function in dilated cardiomyopathy and to investigate if parameters of atrial function are more impaired in Chagas dilated cardiomyopathy (CDC) than in idiopathic dilated cardiomyopathy (IDC).

METHODS AND RESULTS: Seventy-two patients with dilated cardiomyopathy (36 with CDC and 36 with IDC) and 32 healthy controls were evaluated by tissue Doppler, Doppler-based strain and strain rate (SR) imaging of the left atrium (LA) and right atrium (RA). Peak atrial strain during systole and SR during systole, early and late diastolic SR, were measured at the interatrial septum, LA inferior wall and at the lateral wall of the RA. The clinical characteristics and the parameters of LV function were similar between patients with CDC and IDC. Myocardial deformation indices during the reservoir phase of both RA and LA were lower in patients with dilated cardiomyopathy than in controls, suggesting atrial dysfunction in cardiomyopathies. However, LA and RA deformation parameters did not differ between CDC and IDC patients (interatrial septal strain during the reservoir phase: -25.2 ± 14.8 vs. -24.9 ± 16.0%, P = NS; strain rate during the reservoir phase: -1.3 ± 0.7 vs. -1.5 ± 0.9/s, P = NS).

CONCLUSIONS: Atrial myocardial deformation properties are abnormal in patients with dilated cardiomyopathy. CDC does not seem to have more atrial involvement than IDC.}, } @article {pmid21766182, year = {2012}, author = {Gabrovska, PN and Smith, RA and Tiang, T and Weinstein, SR and Haupt, LM and Griffiths, LR}, title = {Development of an eight gene expression profile implicating human breast tumours of all grade.}, journal = {Molecular biology reports}, volume = {39}, number = {4}, pages = {3879-3892}, pmid = {21766182}, issn = {1573-4978}, mesh = {Axin Protein/genetics/metabolism ; Breast Neoplasms/*genetics/*pathology ; Female ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/*genetics ; Humans ; Immunohistochemistry ; Microarray Analysis ; Middle Aged ; Neoplasm Grading ; Polymerase Chain Reaction ; }, abstract = {The goal of improving systemic treatment of breast cancers is to evolve from treating every patient with non-specific cytotoxic chemotherapy/hormonal therapy, to a more individually-tailored direct treatment. Although anatomic staging and histological grade are important prognostic factors, they often fail to predict the clinical course of this disease. This study aimed to develop a gene expression profile associated with breast cancers of differing grades. We extracted mRNA from FFPE archival breast IDC tissue samples (Grades I-III), including benign tumours. Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Arrays were used to determine gene expression profiles and validated by Q-PCR. IHC was used to detect the AXIN2 protein in all tissues. From the array data, an independent group t-test revealed that 178 genes were significantly (P ≤ 0.01) differentially expressed between three grades of malignant breast tumours when compared to benign tissues. From these results, eight genes were significantly differentially expressed in more than one comparison group and are involved in processes implicated in breast cancer development and/or progression. The two most implicated candidates genes were CLD10 and ESPTI1 as their gene expression profile from the microarray analysis was replicated in Q-PCR analyses of the original tumour samples as well as in an extended population. The IHC revealed a significant association between AXIN2 protein expression and ER status. It is readily acknowledged and established that significant differences exist in gene expression between different cancer grades. Expansion of this approach may lead to an improved ability to discriminate between cancer grade and other pathological factors.}, } @article {pmid21761341, year = {2011}, author = {Chanplakorn, N and Chanplakorn, P and Suzuki, T and Ono, K and Wang, L and Chan, MS and Wing, L and Yiu, CC and Chow, LW and Sasano, H}, title = {Increased 5α-reductase type 2 expression in human breast carcinoma following aromatase inhibitor therapy: the correlation with decreased tumor cell proliferation.}, journal = {Hormones & cancer}, volume = {2}, number = {1}, pages = {73-81}, pmid = {21761341}, issn = {1868-8500}, mesh = {17-Hydroxysteroid Dehydrogenases/biosynthesis ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/*biosynthesis ; Androstadienes/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Aromatase Inhibitors/*therapeutic use ; Breast Neoplasms/*drug therapy/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/*metabolism ; Celecoxib ; Cell Proliferation/*drug effects ; Female ; Humans ; Immunohistochemistry ; Letrozole ; Neoadjuvant Therapy ; Nitriles/administration & dosage ; Pyrazoles/administration & dosage ; Receptors, Androgen/biosynthesis ; Sulfonamides/administration & dosage ; Treatment Outcome ; Triazoles/administration & dosage ; }, abstract = {Tumor cell proliferation and progression of breast cancer are influenced by female sex steroids. However, not all breast cancer patients respond to aromatase inhibitors (AI), and many patients become unresponsive or relapse. Recent studies demonstrate that not only estrogens but also androgens may serve as regulators of estrogen-responsive as well as estrogen-unresponsive human breast cancers. However, the mechanism underlying these androgenic actions has remained relatively unknown. Therefore, in this study, we evaluated the effects of AI upon the expression of enzymes involved in intratumoral androgen production including 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5), 5α-reductase types 1 and 2 (5αRed1 and 5αRed2) as well as androgen receptor (AR) levels and correlated the findings with therapeutic responses including Ki67 labeling index (Ki67). Eighty-two postmenopausal invasive ductal carcinoma patients were enrolled in CAAN study from November 2001 to April 2004. Pre- and post-treatment specimens of 29 cases were available for this study. The status of 17βHSD5, 5αRed1, 5αRed2, and Ki67 in pre- and post-treatment specimens were evaluated. The significant increments of 5αRed2 as well as AR were detected in biological response group whose Ki67 LI decreased by more than 40% of the pre-treatment level. This is the first study demonstrating an increment of 5αRed2 and AR in the group of the patients associated with Ki67 decrement following AI treatment. These results suggest that increased 5αRed2 and AR following AI treatment may partly contribute to reduce the tumor cell proliferation through increasing intratumoral androgen concentrations and its receptor.}, } @article {pmid21756827, year = {2011}, author = {Zhang, N and Sun, ZZ and Li, F and Cao, YW and Zhao, CX and Liang, WH and Sun, HP and Li, HA and Fu, XG}, title = {[Detection and clinical significance of Notch1 methylation in breast cancer and intraductal proliferative breast lesions].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {40}, number = {5}, pages = {324-329}, pmid = {21756827}, issn = {0529-5807}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; CpG Islands/genetics ; *DNA Methylation ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Precancerous Conditions/genetics/metabolism/pathology ; Promoter Regions, Genetic ; Receptor, Notch1/*genetics/metabolism ; Young Adult ; }, abstract = {OBJECTIVE: To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.

METHODS: Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method).

RESULTS: Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05).

CONCLUSIONS: There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.}, } @article {pmid21744349, year = {2011}, author = {Ruidiaz, ME and Cortes-Mateos, MJ and Sandoval, S and Martin, DT and Wang-Rodriguez, J and Hasteh, F and Wallace, A and Vose, JG and Kummel, AC and Blair, SL}, title = {Quantitative comparison of surgical margin histology following excision with traditional electrosurgery and a low-thermal-injury dissection device.}, journal = {Journal of surgical oncology}, volume = {104}, number = {7}, pages = {746-754}, doi = {10.1002/jso.22012}, pmid = {21744349}, issn = {1096-9098}, mesh = {Adult ; Aged ; Biopsy ; Breast Neoplasms/*pathology/*surgery ; Burns/etiology/pathology/*prevention & control ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Collagen ; Diagnostic Errors/*prevention & control ; Electrosurgery/adverse effects/*instrumentation ; Female ; Humans ; Mastectomy, Segmental/adverse effects/*instrumentation ; Middle Aged ; Neoplasm, Residual/pathology ; Pilot Projects ; Prospective Studies ; Protein Denaturation ; Sensitivity and Specificity ; Soft Tissue Injuries/etiology/pathology/*prevention & control ; }, abstract = {BACKGROUND: This study is the first to examine in vivo the effect of thermal injury in breast conservation pathology in a direct comparison of traditional electrosurgery and an alternative low-thermal-injury device.

METHODS: A prospective study of 20 consecutive subjects with biopsy-proven invasive ductal carcinoma (IDC) tumors 1 cm was conducted. Following excision, incisions were made into the tumor with the two devices. Thermal injury depth, margin distance, tissue type, and histological effect were compared on the same breast tissue cut with each excision instrument. A probability evaluation of close and positive margin cases for the true tumor margins was conducted.

RESULTS: Compared to traditional electrosurgery, the low-thermal-injury instrument reduced collagen denaturation depth from 435 to 102 µm (77%), fused tissue depth from 262 to 87 µm (67%), and distortion depth from 1,132 to 774 µm (30%).

CONCLUSIONS: Based on analysis of the close subset of the true margins, using the traditional electrosurgical device in place of the low-thermal-injury device would have resulted in 48% of the close margin samples being negatively converted to false-positive, and in 11% converting from close to false-negative. The methodology of this work may be readily applied to larger, more definitive studies.}, } @article {pmid21741518, year = {2011}, author = {Miyake, T and Shimazu, K and Ohashi, H and Taguchi, T and Ueda, S and Nakayama, T and Kim, SJ and Aozasa, K and Tamaki, Y and Noguchi, S}, title = {Indication for sentinel lymph node biopsy for breast cancer when core biopsy shows ductal carcinoma in situ.}, journal = {American journal of surgery}, volume = {202}, number = {1}, pages = {59-65}, doi = {10.1016/j.amjsurg.2010.09.032}, pmid = {21741518}, issn = {1879-1883}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; *Sentinel Lymph Node Biopsy ; Young Adult ; }, abstract = {BACKGROUND: The use of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is controversial.

METHODS: A total of 103 primary breast cancer patients who were diagnosed with DCIS by needle biopsy preoperatively and underwent initial SLNB were analyzed retrospectively.

RESULTS: No sentinel nodal metastasis was detected in 66 patients with the final diagnosis of DCIS. However, 2 (5.4%) of 37 patients with invasive ductal carcinoma at final diagnosis had positive sentinel nodes. Multivariate logistic regression analysis identified 2 independent significant predictors of existence of invasive components: presence of a palpable tumor (odds ratio, 4.091; 95% confidential interval, 1.399-11.959; P = .010) and tumor size of 2.0 cm or larger on magnetic resonance imaging (odds ratio, 4.506; 95% confidence interval, 1.322-15.358; P = .016).

CONCLUSIONS: Initial SLNB should be considered for patients diagnosed with DCIS by needle biopsy when they have a high risk for harboring invasive ductal cancer preoperatively.}, } @article {pmid21740834, year = {2011}, author = {Lu, H and Xu, YL and Zhang, SP and Lang, RG and Zee, CS and Liu, PF and Fu, L}, title = {Breast magnetic resonance imaging in patients with occult breast carcinoma: evaluation on feasibility and correlation with histopathological findings.}, journal = {Chinese medical journal}, volume = {124}, number = {12}, pages = {1790-1795}, pmid = {21740834}, issn = {2542-5641}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {BACKGROUND: As an uncommon presentation, occult primary breast cancer remains a diagnostic and therapeutic challenge in clinical practice. This study aimed to retrospectively assess the feasibility of breast magnetic resonance imaging (MRI) in patients with malignant axillary lymphadenopathy and unknown primary malignancy, and correlation with histopathological characteristics.

METHODS: A total of 35 women with occult breast carcinoma were evaluated with dynamic contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI performance was assessed and correlated with histopathological findings.

RESULTS: Twenty-one of 35 patients were found to have primary breast carcinoma histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient had a normal MRI study. Of the remaining 14 patients, 10 were negative on both MRI and surgery. Four had suspicious enhancement on MRI and no corresponding tumor was found. Lesions with mass enhancement were found in 55% (11/20) and ductual and segmental enhancement in 45%. The average diameter of the primary tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17 invasive ductual carcinomas was too small to be graded. Fourteen of the remaining 16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients had received estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 examinations and the 12 of 32 were triple-negative breast carcinoma.

CONCLUSIONS: Mass lesions with small size and lesions with ductal or segment enhancement are common MRI features in patients with occult breast cancer. The dominant types of primary tumors are invasive ductal carcinoma with moderate histopathological grade. The rate of triple-negative breast carcinoma may be higher in occult breast cancer.}, } @article {pmid21738806, year = {2011}, author = {Teixeira, PC and Santos, RH and Fiorelli, AI and Bilate, AM and Benvenuti, LA and Stolf, NA and Kalil, J and Cunha-Neto, E}, title = {Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.}, journal = {PLoS neglected tropical diseases}, volume = {5}, number = {6}, pages = {e1205}, pmid = {21738806}, issn = {1935-2735}, mesh = {ATP Synthetase Complexes/genetics/*metabolism ; Adolescent ; Adult ; Chagas Cardiomyopathy/*physiopathology ; Creatine Kinase, Mitochondrial Form/genetics/*metabolism ; Gene Expression Profiling ; Humans ; Immunoblotting ; Male ; Middle Aged ; Myocardium/*enzymology ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies.

Myocardium homogenates from CCC (N=5), IC (N=5) and IDC (N=5) patients, as well as from heart donors (N=5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels.

CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.}, } @article {pmid21737659, year = {2011}, author = {Jiang, L and Ma, T and Moran, MS and Kong, X and Li, X and Haffty, BG and Yang, Q}, title = {Mammographic features are associated with clinicopathological characteristics in invasive breast cancer.}, journal = {Anticancer research}, volume = {31}, number = {6}, pages = {2327-2334}, pmid = {21737659}, issn = {1791-7530}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; }, abstract = {AIM: To assess the correlation between mammographic features and clinicopathologic characteristics of invasive breast carcinoma.

PATIENTS AND METHODS: The mammographic appearance and clinicopathological data of 108 invasive ductal carcinomas were retrospective analyzed. The mammographic features were assessed according to BI-RADS by two doctors. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2) and Ki-67 were analyzed on the surgically removed tumor samples by immunohistochemical staining analysis. The clinical information, including age, menopausal status, tumor size, grade, stage, and axillary lymph node status, were collected from our database. Statistical analysis was performed to assess the correlation between mammographic features and clinicopathologic characteristics.

RESULTS: Based on pathologic analysis, 19 out of the 108 (18%) patients had invasive ductal carcinoma (IDC) accompanied by component of ductal carcinoma in situ (DCIS); another 89 cases (82%) were pure IDC. Sixty-three patients had a mass on the mammogram; the mammographically visible mass was frequently observed in histologically pure IDC, while mammographic calcification was significantly associated with IDC accompanied with DCIS (p<0.01). Mammographic calcification accompanied by evident mass was correlated with axillary lymph node metastasis (p<0.05). The tumor size was usually larger than 2 cm when the mammographic mass was accompanied by calcification (p<0.01). Tumors from patients presenting with spiculated mass had a significantly higher ER-positive and PR-positive rates than those from patients presenting with non-spiculated mass (92.59% vs. 63.89%, p<0.01, and 92.59% vs. 44.44%, p<0.01, respectively). Tumors from patients presenting with spiculated mass had Her2 negativity (p<0.05) and lower proliferative activity as labeled by Ki-67 compared with those from patients presenting with non-spiculated mass (p<0.01).

CONCLUSION: Based on our current findings, the mammographic appearance reflects the biologic behavior of the breast tumor and should be taken into account when planning treatment for IDC.}, } @article {pmid21733550, year = {2012}, author = {Choi, Y and Kim, EJ and Seol, H and Lee, HE and Jang, MJ and Kim, SM and Kim, JH and Kim, SW and Choe, G and Park, SY}, title = {The hormone receptor, human epidermal growth factor receptor 2, and molecular subtype status of individual tumor foci in multifocal/multicentric invasive ductal carcinoma of breast.}, journal = {Human pathology}, volume = {43}, number = {1}, pages = {48-55}, doi = {10.1016/j.humpath.2010.08.026}, pmid = {21733550}, issn = {1532-8392}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Nucleus/genetics/metabolism/pathology ; DNA, Neoplasm/analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/genetics/*metabolism/pathology ; Phenotype ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Steroid/genetics/*metabolism ; Tissue Array Analysis ; Young Adult ; }, abstract = {Multifocal/multicentric breast cancers are common. However, investigations of biomarkers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in individual tumor foci of such cancers are rare. This study was designed to evaluate the status of the hormone receptors, human epidermal growth factor receptor 2, and its molecular subtypes in individual foci of multifocal/multicentric invasive ductal carcinoma of the breast and to identify the factors associated with the different phenotypes of individual foci. We performed immunohistochemical analyses of the estrogen receptor, progesterone receptor, cytokeratin 5/6, epidermal growth factor receptor, and p53 and fluorescence in situ hybridization of human epidermal growth factor receptor 2 in individual foci of 65 cases of multifocal/multicentric invasive ductal carcinoma and the associated ductal carcinoma in situ components using tissue microarrays. The estrogen receptor status differed in 2 (3%) of the 65 invasive ductal carcinomas, progesterone receptor status in 7 (11%), human epidermal growth factor receptor 2 status in 4 (6%), and molecular subtypes in 5 (8%). The presence of different molecular subtypes in the invasive tumor foci was associated with differences in histologic features (P = .005), high histologic and nuclear grade (P = .012 and P = .021, respectively), p53 overexpression (P = .006), and mixed molecular subtypes in the ductal carcinoma in situ components (P = .011). Multifocal/multicentric invasive ductal carcinomas usually have a single phenotype in terms of hormone receptors, human epidermal growth factor receptor 2, and molecular subtypes; and thus, immunohistochemical analyses of the index tumor may be sufficient in routine practice. However, if multifocal/multicentric invasive ductal carcinomas are of high grade, of different histologic features, or of heterogeneous ductal carcinoma in situ component, biomarkers of the various foci need to be evaluated separately.}, } @article {pmid21732779, year = {2011}, author = {Papalas, JA and Wylie, JD and Dash, RC}, title = {Recurrence risk and margin status in granular cell tumors of the breast: a clinicopathologic study of 13 patients.}, journal = {Archives of pathology & laboratory medicine}, volume = {135}, number = {7}, pages = {890-895}, doi = {10.5858/2010-0430-OAR.1}, pmid = {21732779}, issn = {1543-2165}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/surgery ; Female ; Granular Cell Tumor/*pathology/surgery ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Prognosis ; Recurrence ; Risk ; }, abstract = {CONTEXT: Granular cell tumors (GCTs) of the breast are rare neoplasms that mimic epithelial malignancy clinically and rarely occur in association with it. Granular cell tumors of the breast are not infrequently excised with positive margins. Reports describing risk of recurrence including data on margin status and follow-up are lacking.

OBJECTIVE: To review our series of GCTs of the breast to determine the risk of recurrence if excised with positive or close margins.

DESIGN: Cases of GCT of the breast were reviewed. Margin status of specimens was recorded as positive, close (<1 mm), and negative.

RESULTS: Thirteen female patients with GCT of the breast were identified. Mean patient age at presentation was 45 years. Seventy-seven percent of patients were African American and 23% were white. African American patients presented on average 13 years earlier than white patients. Average tumor size was 1.22 cm. Fifteen percent of lesions had positive margins on excisional biopsy or lumpectomy and 31% had tumor cells within 1 mm of the margin. One of 13 patients (8%) had coexistent invasive ductal carcinoma. Average follow-up for the entire group was 77 months. Patients with positive margins remained free of tumor progression or recurrence for 89 months and patients with close margins also remained disease free during a 64-month follow-up period. No tumors recurred out of the entire group.

CONCLUSION: Granular cell tumors of the breast have little long-term risk for recurrence, even when excised with positive margins. Surgical evaluation after nonexcisional biopsy may still be indicated to assess for the possible association of colocalized carcinoma.}, } @article {pmid21724529, year = {2011}, author = {Samir, SM and Fayaz, MS and Elbasmi, A and Motawy, MM and Abuzallouf, S and George, T and Abdelhady, M and Bedair, A}, title = {Medullary carcinoma of the breast: ten year clinical experience of the Kuwait cancer control centre.}, journal = {The Gulf journal of oncology}, volume = {}, number = {10}, pages = {45-52}, pmid = {21724529}, issn = {2078-2101}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*mortality/pathology ; Carcinoma, Medullary/chemistry/*mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; }, abstract = {BACKGROUND: Medullary carcinomas of the breast account for fewer than 7% of all invasive breast cancers. Some investigators include medullary carcinomas in the favourable histologic subtype, despite its aggressive histologic appearance. However, others fail to confirm its favourable prognosis.

METHODS: This was a retrospective analysis of sixty-one (61) cases of breast cancer cases diagnosed with Medullary Carcinoma, presenting to the Kuwait Cancer Control Center between 1995 and 2005.

RESULTS: Median survival time was 122 months and the seven-year disease free survival was 82%. Overall survival rate was not assessed as no cases died during the study period. No cases were metastatic from the start and only eight cases developed metastases, local recurrence or contralateral breast primary. 68.8% of the cases were Stage I or IIA (i.e. no lymph node affection).

CONCLUSION: There is no overt favourable prognosis of medullary carcinoma when compared to invasive ductal carcinoma. Prognosis is more related to stage than histologic subtyping. The majority of cases were negative estrogen and progesterone receptor status and node negative.}, } @article {pmid21722359, year = {2011}, author = {Poulias, E and Melakopoulos, I and Tosios, K}, title = {Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report.}, journal = {Journal of medical case reports}, volume = {5}, number = {}, pages = {265}, pmid = {21722359}, issn = {1752-1947}, abstract = {INTRODUCTION: Tumors can metastasize to the oral cavity and affect the jaws, soft tissue and salivary glands. Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Because of their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. The purpose of this report is to present a rare case of a metastatic breast carcinoma mimicking a periodontal abscess in the mandible.

CASE PRESENTATION: A 55-year-old Caucasian woman was referred to our clinic for evaluation of bisphosphonate-induced jaw osteonecrosis. She had undergone modified radical mastectomy with axillary lymph node dissection for invasive ductal carcinoma of the left breast. Her clinical examination showed diffuse swelling and a periodontal pocket of 6 mm exhibiting suppuration in the posterior right mandible. Moreover, paresthesia of the lower right lip and chin was noted. There were no significant radiographic findings other than alveolar bone loss due to her periodontal disease. Although the lesion resembled a periodontal abscess, metastatic carcinoma of the breast was suspected on the basis of the patient's medical history. The area was biopsied, and histological analysis confirmed the final diagnosis of metastatic breast carcinoma.

CONCLUSION: The general dentist or dental specialist should maintain a high level of suspicion while evaluating patients with a history of cancer. Paresthesias of the lower lip and the chin should be considered ominous signs of metastatic disease. This case highlights the importance of the value of a detailed medical history and thorough clinical examination for the early detection of metastatic tumors in the oral cavity.}, } @article {pmid21715690, year = {2011}, author = {Kis-Toth, K and Hajdu, P and Bacskai, I and Szilagyi, O and Papp, F and Szanto, A and Posta, E and Gogolak, P and Panyi, G and Rajnavolgyi, E}, title = {Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {187}, number = {3}, pages = {1273-1280}, doi = {10.4049/jimmunol.1003345}, pmid = {21715690}, issn = {1550-6606}, mesh = {Cell Differentiation/immunology ; Cell Movement/*immunology ; Cells, Cultured ; Chemokines/*physiology ; Cytokines/metabolism ; Dendritic Cells/cytology/*immunology/*metabolism ; Humans ; Membrane Potentials/*immunology ; Monocytes/cytology/*immunology/*metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; Resting Phase, Cell Cycle/immunology ; Sodium Channels/*physiology ; }, abstract = {Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.}, } @article {pmid21713550, year = {2012}, author = {Tiezzi, DG and Valejo, FA and Marana, HR and Carrara, HH and Benevides, L and Antonio, HM and Sicchieri, RD and Milanezi, CM and Silva, JS and de Andrade, JM}, title = {CD44+/CD24- cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {3}, pages = {1479-1485}, pmid = {21713550}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; CD24 Antigen/analysis ; Carcinoma, Ductal, Breast/*pathology ; Female ; Flow Cytometry ; Humans ; Hyaluronan Receptors/analysis ; Immunohistochemistry ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neoplastic Stem Cells/*pathology ; }, abstract = {The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumor-initiating cells in stage I and II breast cancer.}, } @article {pmid21712309, year = {2011}, author = {Fernández, B and Paish, EC and Green, AR and Lee, AH and Macmillan, RD and Ellis, IO and Rakha, EA}, title = {Lymph-node metastases in invasive lobular carcinoma are different from those in ductal carcinoma of the breast.}, journal = {Journal of clinical pathology}, volume = {64}, number = {11}, pages = {995-1000}, doi = {10.1136/jclinpath-2011-200151}, pmid = {21712309}, issn = {1472-4146}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology/*secondary ; Carcinoma, Lobular/pathology/*secondary ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Survival Analysis ; }, abstract = {AIM: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast are distinct morphological entities with different biological features and clinical behaviour. In the present study, the authors compare the axillary-lymph-node (ALN) status of patients with grade-matched ILC (no=426) and IDC (no=820). The pattern of nodal metastatic deposits (nodular, sinusoidal and diffuse) and the proportion of involved nodes were also analysed in a selected group of 246 tumours, which were associated with a single positive ALN.

RESULTS: Compared with grade-matched IDC, ILC was associated with a higher nodal stage (13.1% vs 4.5% of ILC and IDC were stage 3), higher absolute number of positive nodes and higher ratio of positive nodes (0.46±0.30 and 0.33±0.23 in ILC and IDC respectively). These differences were maintained in the different size subgroups. The most common metastatic morphological pattern was nodular in both types of carcinomas. A sinusoidal pattern was more frequent in IDC, and the diffuse pattern was more frequent in ILC. Despite these differences, ILC and grade-matched IDC exhibited similar rates of regional recurrences (RR) and breast-cancer survival.

CONCLUSION: This study provides clinical evidence which further demonstrates that ILC and IDC are biologically distinct entities with different lymph-node involvement patterns and ILC having a tendency to metastasise to more nodes than IDC. However, this difference was not associated with a significant impact on patient outcome.}, } @article {pmid21710692, year = {2011}, author = {Moelans, CB and Verschuur-Maes, AH and van Diest, PJ}, title = {Frequent promoter hypermethylation of BRCA2, CDH13, MSH6, PAX5, PAX6 and WT1 in ductal carcinoma in situ and invasive breast cancer.}, journal = {The Journal of pathology}, volume = {225}, number = {2}, pages = {222-231}, doi = {10.1002/path.2930}, pmid = {21710692}, issn = {1096-9896}, mesh = {Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA Methylation/*genetics ; DNA-Binding Proteins/genetics ; Eye Proteins/genetics ; Female ; Genes, BRCA2 ; Genes, Wilms Tumor ; Homeodomain Proteins/genetics ; Humans ; Microdissection ; PAX5 Transcription Factor/genetics ; PAX6 Transcription Factor ; Paired Box Transcription Factors/genetics ; Promoter Regions, Genetic/*genetics ; Repressor Proteins/genetics ; }, abstract = {Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism to inactivate tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. In search of epigenetic events related to progression, we used MS-MLPA (ME-0002-B1, MRC-Holland, Amsterdam, The Netherlands) to compare the methylation status of 25 breast cancer-related genes between laser-microdissected ductal carcinoma in situ (DCIS) and adjacent invasive ductal cancer (IDC) lesions in 33 breast cancer patients. Using absolute methylation percentages or, alternatively, a 15% cut-off for methylation, promoter methylation in DCIS and IDC was not significantly different for any of the genes studied. Aberrant methylation in at least 50% of both the DCIS and adjacent IDC lesions was observed for PAX6, BRCA2, PAX5, WT1, CDH13 and MSH6. Methylation of MSH6, however, was also frequent in normal breast tissue. In contrast, CDKN2A, CHFR, PYCARD and one of the two analysed RB1 CpG loci were rarely (<5%) methylated in both lesions. CDKN2A and GSTP1 showed significantly (p < 0.002) higher mean methylation levels in increasing grades (I, II, III) of DCIS (1% versus 4% versus 7% for CDKN2A and 6% versus 26% versus 28% for GSTP1). The mean number of methylated genes per sample increased with increasing grades of DCIS (p = 0.014) and IDC (p = 0.109). In contrast to the observations in DCIS, none of the analysed genes showed significantly higher methylation levels with increasing grades of IDC. In conclusion, there were no differences in promoter methylation between DCIS and IDC in the 25 analysed genes, suggesting that DCIS, at the epigenetic level, is as advanced as IDC. Promoter hypermethylation of PAX6, BRCA2, PAX5, WT1, CDH13 and MSH6 seems to be a frequent early event in breast cancer and methylation levels of GSTP1 (and CDKN2A, although still low) seem to increase with increasing DCIS grade.}, } @article {pmid21710579, year = {2012}, author = {Shahar, B and Carlin, ER and Engle, DE and Hegde, J and Szepsenwol, O and Arkowitz, H}, title = {A pilot investigation of emotion-focused two-chair dialogue intervention for self-criticism.}, journal = {Clinical psychology & psychotherapy}, volume = {19}, number = {6}, pages = {496-507}, doi = {10.1002/cpp.762}, pmid = {21710579}, issn = {1099-0879}, mesh = {Adult ; Anxiety/prevention & control ; Depression/prevention & control ; *Emotions ; Empathy ; Female ; Humans ; Mental Disorders/*psychology/*rehabilitation ; Middle Aged ; Pilot Projects ; Psychotherapeutic Processes ; Psychotherapy, Brief/*methods ; *Self Concept ; *Self-Assessment ; }, abstract = {UNLABELLED: Self-criticism plays a key role in many psychological disorders and predicts poor outcome in psychotherapy. Yet, psychotherapy research directly targeting self-critical processes is limited. In this pilot study, we examined the efficacy of an emotion-focused intervention, the two-chair dialogue task, on self-criticism, self-compassion and the ability to self-reassure in times of stress, as well as on depressive and anxiety symptoms among nine self-critical clients. Results showed that the intervention was associated with significant increases in self-compassion and self-reassuring, and significant reductions in self-criticism, depressive symptoms and anxiety symptoms. Effect sizes were medium to large, with most clients exhibiting low and non-clinical levels of symptomatology at the end of therapy, and maintaining gains over a 6-month follow-up period. Although preliminary, these finding suggest that emotion-focused chair work might be a promising intervention addressing self-criticism.

KEY PRACTITIONER MESSAGE: Self-criticism is an important process in a variety of clinical disorders and predicts poor outcome in brief therapy for depression. Yet, little is known about how self-criticism can be effectively addressed in psychological treatment. Practitioners can benefit from increasing their awareness of self-critical processes in their clinical work, and from directly working with emotions in addressing self-criticisim. Emotion-focused two-chair dialogue intervention can be effective in reducing self-criticism, increasing self-compassion, and decreasing depressive and anxiety symptoms, and these improvements are largely maintained six months after therapy.}, } @article {pmid21709012, year = {2011}, author = {Zagouri, F and Sergentanis, TN and Provatopoulou, X and Kalogera, E and Chrysikos, D and Lymperi, M and Papadimitriou, CA and Zografos, E and Bletsa, G and Kalles, VS and Zografos, GC and Gounaris, A}, title = {Serum levels of HSP90 in the continuum of breast ductal and lobular lesions.}, journal = {In vivo (Athens, Greece)}, volume = {25}, number = {4}, pages = {669-672}, pmid = {21709012}, issn = {1791-7549}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/*blood/*pathology ; Breast Neoplasms/blood/pathology ; Carcinoma, Ductal, Breast/blood/pathology ; Carcinoma, Intraductal, Noninfiltrating/blood/pathology ; Carcinoma, Lobular/blood/pathology ; Female ; HSP90 Heat-Shock Proteins/*blood ; Humans ; Hyperplasia/blood/pathology ; Middle Aged ; }, abstract = {BACKGROUND: Heat-shock protein 90 (HSP90) is an abundant protein in mammalian cells. It interacts with a variety of proteins that play key roles in breast neoplasia. This is the first study to assess serum levels of HSP90 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and infiltrative lobular carcinoma (ILC).

PATIENTS AND METHODS: Serum concentrations of HSP90 in women with benign (n=34), ADH (n=26), DCIS (n=30), IDC (n=29), LN (n=20) and ILC (n=9) lesions were determined with immunoenzymatic assays. For the evaluation of serum concentrations along the transition from benign through precursor and preinvasive to invasive lesion, the severity of diagnosis was treated as an ordinal variable.

RESULTS: No significant association was demonstrated between serum HSP90 levels and the severity of the lesion in ductal and lobular series. The post hoc comparison between the lobular and ductal precursor lesions (i.e. ADH vs. LN) did not yield a statistically significant difference. Similarly, the post hoc comparison between the lobular and ductal invasive carcinomas (i.e. IDC vs. ILC) did not point to a statistically significant difference.

CONCLUSION: This is the first study evaluating HSP90 serum levels in both lobular and ductal lesions of the breast. Contrary to published pathological findings according to which HSP90 exhibits significant variability along both series, such a finding was not replicated for the level of serum HSP90 concentrations.}, } @article {pmid21707845, year = {2011}, author = {Shui, R and Bi, R and Cheng, Y and Lu, H and Wang, J and Yang, W}, title = {Matrix-producing carcinoma of the breast in the Chinese population: a clinicopathological study of 13 cases.}, journal = {Pathology international}, volume = {61}, number = {7}, pages = {415-422}, doi = {10.1111/j.1440-1827.2011.02676.x}, pmid = {21707845}, issn = {1440-1827}, mesh = {Adenocarcinoma/metabolism/*secondary/therapy ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*secondary/therapy ; Cell Nucleus/metabolism/pathology ; Combined Modality Therapy ; Extracellular Matrix/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Second Primary ; Retrospective Studies ; }, abstract = {Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic carcinoma. The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression profile of this rare tumor in Chinese population. Thirteen cases of MPC were evaluated using morphology observation and immunohistochemistry. All tumors had invasive carcinoma with an abrupt transition to chondromyxoid matrix without an intervening spindle cell sarcomatoid component. The distribution of tumor cells was diffuse in eight cases and peripheral in five cases. Matrix distribution was diffuse or multifocal. Necrosis was present in 11 cases. An overt invasive ductal carcinoma was observed in 11 cases and the other two tumors were consistent with MPC arising in microglandular adenosis. Ten of 13 cases were triple negative (ER-, PR-, Her2/neu-). Eight of 10 triple negative cases were cytokeratin 5/6, cytokeratin 14 or epidermal growth factor receptor positive, consistent with the basal-like phenotype. S-100 protein was positive in all cases. At the time of initial diagnosis, one of 13 patients had lung metastasis and axillary lymph nodes metastasis. Follow-up time ranged from 6 to 30 months. All patients remained alive. One patient developed a soft tissue metastasis 24 months after surgery.}, } @article {pmid21702220, year = {2011}, author = {Damle, AA and Narkar, AA and Badwe, RA}, title = {Radioiodide uptake and sodium iodide symporter expression in breast carcinoma.}, journal = {Indian journal of experimental biology}, volume = {49}, number = {6}, pages = {416-422}, pmid = {21702220}, issn = {0019-5189}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/*radiotherapy ; Female ; Gene Expression ; Humans ; Iodine Radioisotopes/pharmacokinetics/*therapeutic use ; Middle Aged ; RNA, Neoplasm/genetics/metabolism ; Symporters/*genetics ; }, abstract = {Breast cancer is a common malignancy in women all over the world and novel therapeutic approaches are required for the treatment of patients who become refractory to conventional therapies. Thyroid cancer is being treated successfully with radioiodine since many years. The iodide is transported inside the thyroid epithelial cell via sodium iodide symporter (NIS) which is a trans-membrane protein. The present study was aimed to explore the uptake of radioiodide (RAI) and the expression of NIS in breast tissues of invasive ductal carcinoma patients. Breast tissues from tumor region (Tu-Br) as well as corresponding normal region (N-Br) were collected from patients of invasive ductal carcinoma. In vitro RAI uptake, its efflux and NIS expression were studied. The uptake of RAI (1.98+/-1.75 x 10(5) cpm/g) in Tu-Br was significantly higher as compared to that observed in N-Br (0.31+/-0.27 x 10(5) cpm/g) and fast efflux was observed in the tissue samples. NIS gene expression was positive in 41.66% (10/24) samples of Tu-Br. None of the N-Br samples expressed NIS gene. In 14 samples of Tu-Br, RAI uptake as well as NIS expression was studied. In 50% of these Tu-Br samples RAI uptake as well as of NIS gene expression was positive. The results indicate that RAI uptake is significantly higher in breast tumor tissues as compared to their normal counterpart and in future radioiodine may be an important agent for treatment of breast cancer.}, } @article {pmid21699039, year = {2011}, author = {Rappaport, A and Van Steen, A and Van Ongeval, C}, title = {A rare presentation of breast cancer.}, journal = {JBR-BTR : organe de la Societe royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)}, volume = {94}, number = {2}, pages = {75-77}, doi = {10.5334/jbr-btr.499}, pmid = {21699039}, issn = {0302-7430}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Axilla ; Biopsy ; Breast/microbiology/pathology/surgery ; Breast Neoplasms/complications/*diagnosis/*therapy ; Carcinoma, Ductal, Breast/complications/*diagnosis/*therapy ; Diagnosis, Differential ; Docetaxel ; Female ; Follow-Up Studies ; Granulomatous Mastitis/complications/*diagnosis/*therapy ; Humans ; Lymph Node Excision ; Lymph Nodes/surgery ; Mammography/methods ; Mastectomy ; Positron-Emission Tomography/methods ; Radiotherapy, Adjuvant/methods ; Staphylococcal Infections/complications/diagnosis/drug therapy ; Staphylococcus aureus/drug effects ; Taxoids/therapeutic use ; Tomography, X-Ray Computed/methods ; Ultrasonography, Mammary/methods ; }, abstract = {The case of a 67-year-old woman with a large lump in the left axillary region and the left breast is presented. Pathologic investigation of these masses in 2 hospitals was inconclusive. Further work-up in our radiologic department showed beside the presence of the two tumoral masses, abnormalities with the radiologic characteristics of granulomatous mastitis. Final pathologic analysis showed the presence of an invasive ductal carcinoma in the two masses in combination with a granulomatous stromal reaction.}, } @article {pmid21696617, year = {2011}, author = {Rambau, PF and Chalya, PL and Manyama, MM and Jackson, KJ}, title = {Pathological features of Breast Cancer seen in Northwestern Tanzania: a nine years retrospective study.}, journal = {BMC research notes}, volume = {4}, number = {}, pages = {214}, pmid = {21696617}, issn = {1756-0500}, abstract = {BACKGROUND: Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania.

METHODS: This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15.

FINDINGS: There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3.

CONCLUSION: Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis.}, } @article {pmid21691700, year = {2011}, author = {Martins Junior, DF and Costa, TM and Lordelo, MS and Felzemburg, RD}, title = {Trends of mortality from ill-defined causes in the Northeast region of Brazil, 1979-2009.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {57}, number = {3}, pages = {332-340}, pmid = {21691700}, issn = {1806-9282}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Brazil/epidemiology ; Cause of Death/*trends ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Sex Distribution ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to analyze the trends of mortality from symptoms, signs and ill-defined causes (SSIDC) in the Northeast region of Brazil, during the period of 1979- 2009.

METHODS: The study used secondary data provided by the Mortality Information System SIM/Datasus/Ministry of Health.

RESULTS: There was a reduction in the proportion of this type of death (y = -1.3751x + 55.953 R² = 0.9035), from 45.7% in 1979 to 8.1% in 2009, as well as according to sex: males (y = -1.3716x + 54.559 R² = 0.9197) and females (y = -1.3828x + 57.932 R² = 0.8771). The proportion of deaths due to ill-defined causes showed a decreasing tendency in all age groups. The highest reduction was observed in the upper and lower age ranges, < 1 and 1 to 4 year and elderly group, namely 60 years old and older. Capitals and countryside also showed a decreasing tendency in proportional mortality due to IDC, (y = -0.1118x + 9.4275 R² = 0.3087) and (y = -1.7908x + 71.178 R² = 0.9151) respectively, but with different temporal patterns. The capital cities had the lower rates since the beginning of the series regardless of the age groups, but the great reduction in rates was observed in the countryside, being 7.1 times higher among adults (20 to 59 years old).

CONCLUSION: Decreased trends were observed, but it is necessary to reinforce the actions to improve the capacity of health service assistance and coverage and data registration in order to maintain this trend.}, } @article {pmid21689894, year = {2011}, author = {Catteau, X and Dehou, MF and Dargent, JL and Hackx, M and Noël, JC}, title = {Chronic lymphocytic leukemia mimicking recurrent carcinoma of the breast: case report and review of the literature.}, journal = {Pathology, research and practice}, volume = {207}, number = {8}, pages = {514-517}, doi = {10.1016/j.prp.2011.05.007}, pmid = {21689894}, issn = {1618-0631}, mesh = {Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology ; Leukemic Infiltration/pathology ; Neoplasm Recurrence, Local/*pathology ; Neoplasms, Second Primary/*pathology ; }, abstract = {Secondary localization of chronic lymphocytic leukemia (CLL) in breast is rare, while concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in breast is extremely rare. The observation of a CLL infiltration closely associated with a distinct breast neoplasm with the absence of any other localization for the leukemia is an indisputable argument for a relationship between the two diseases. The presence of both tumors is not simply due to chance. This association (CLL and carcinoma) has also been described in other organs. Hereafter, we report a second case of an 80 year-old woman in whom a leukemic infiltrate was confined to the region immediately surrounding poorly differentiated primary breast carcinoma, and we will discuss the association between CLL and carcinoma.}, } @article {pmid21685944, year = {2012}, author = {Shenoy, SK and Han, S and Zhao, YL and Hara, MR and Oliver, T and Cao, Y and Dewhirst, MW}, title = {β-arrestin1 mediates metastatic growth of breast cancer cells by facilitating HIF-1-dependent VEGF expression.}, journal = {Oncogene}, volume = {31}, number = {3}, pages = {282-292}, pmid = {21685944}, issn = {1476-5594}, support = {R01 HL080525/HL/NHLBI NIH HHS/United States ; CA40355/CA/NCI NIH HHS/United States ; R01 HL080525-04S1/HL/NHLBI NIH HHS/United States ; HL080525/HL/NHLBI NIH HHS/United States ; R01 CA040355/CA/NCI NIH HHS/United States ; }, mesh = {Active Transport, Cell Nucleus/drug effects ; Angiogenesis Inhibitors/pharmacology ; Animals ; Antineoplastic Agents/pharmacology ; Benzamides ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Imatinib Mesylate ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Piperazines/pharmacology ; Protein Stability/drug effects ; Pyrimidines/pharmacology ; Thalidomide/pharmacology ; Transcription, Genetic/drug effects ; Vascular Endothelial Growth Factor A/*biosynthesis ; }, abstract = {β-Arrestins 1 and 2 are multifunctional adaptor proteins originally discovered for their role in desensitizing seven-transmembrane receptor signaling via the heterotrimeric guanine nucleotide-binding proteins. Recently identified roles of β-arrestins include regulation of cancer cell chemotaxis and proliferation. Herein, we report that β-arrestin1 expression regulates breast tumor colonization in nude mice and cancer cell viability during hypoxia. β-Arrestin1 robustly interacts with nuclear hypoxia-induced factor-1α (HIF-1α) that is stabilized during hypoxia and potentiates HIF-1-dependent transcription of the angiogenic factor vascular endothelial growth factor-A (VEGF-A). Increased expression of β-arrestin1 in human breast cancer (infiltrating ductal carcinoma or IDC and metastatic IDC) correlates with increased levels of VEGF-A. While the anti-angiogenic drug thalidomide inhibits HIF-1-dependent VEGF transcription in breast carcinoma cells, it does not prevent HIF-1α stabilization, but leads to aberrant localization of HIF-1α to the perinuclear compartments and surprisingly stimulates nuclear export of β-arrestin1. Additionally, imatinib mesylate that inhibits release of VEGF induces nuclear export of β-arrestin1-HIF-1α complexes. Our findings suggest that β-arrestin1 regulates nuclear signaling during hypoxia to promote survival of breast cancer cells via VEGF signaling and that drugs that induce its translocation from the nucleus to the cytoplasm could be useful in anti-angiogenic and breast cancer therapies.}, } @article {pmid21683981, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Prognostic significance of mitotic figures in metastatic mammary ductal carcinoma to the lymph nodes.}, journal = {Human pathology}, volume = {42}, number = {12}, pages = {1823-1832}, doi = {10.1016/j.humpath.2011.02.015}, pmid = {21683981}, issn = {1532-8392}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Chemotherapy, Adjuvant ; Disease Progression ; Female ; Fibrosis/pathology ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mitotic Index/*statistics & numerical data ; Neoplasm Grading ; Neoplasm Recurrence, Local/pathology ; Predictive Value of Tests ; Prognosis ; Survival Analysis ; Tumor Suppressor Protein p53/*analysis ; Young Adult ; }, abstract = {We previously reported that the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes accurately predicted the outcome of patients with invasive ductal carcinoma with nodal metastasis. To confirm these previous findings, the present study investigated the number of mitotic figures and other histologic characteristics in metastatic mammary carcinoma to the lymph nodes and their associations with patient outcome according to nodal status and the histologic grade of primary invasive ductal carcinomas in a different series of 1039 patients with invasive ductal carcinoma. Multivariate analyses examining well-known clinicopathologic factors, the number of mitotic figures in the primary invasive ductal carcinomas, the grading system for lymph vessel tumor emboli, the p53 Allred score risk classes of tumor-stromal fibroblasts forming and not forming a fibrotic focus, and 9 histologic features of metastatic mammary carcinoma to the lymph nodes were performed. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes significantly increased the hazard ratios for tumor recurrence and tumor-related death among patients with invasive ductal carcinoma as a whole, those with nodal metastasis, and those with a histologic grade of 2 or 3. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes also significantly increased the hazard ratio for tumor recurrence among patients with histologic grade 1 invasive ductal carcinoma. In conclusion, this study clearly confirmed the excellent outcome predictive power of the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes.}, } @article {pmid21683430, year = {2012}, author = {Serra, KP and Sarian, LO and Rodrigues-Peres, RM and Vassallo, J and Soares, FA and Pinto, GA and da Cunha, IW and Shinzato, JY and Derchain, SF}, title = {Expression of cyclooxygenase-2 (COX-2) and p53 in neighboring invasive and in situ components of breast tumors.}, journal = {Acta histochemica}, volume = {114}, number = {3}, pages = {226-231}, doi = {10.1016/j.acthis.2011.05.001}, pmid = {21683430}, issn = {1618-0372}, mesh = {Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal/genetics/metabolism/*pathology ; Cyclooxygenase 2/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Tumor Microenvironment ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {The aim of the study was to assess the relationship between the expression of COX-2 and p53, hormone receptors and HER-2 in the in situ (DCIS) and invasive components of ductal carcinomas (IDC) of the same breast. The expression of COX-2, p53, and hormone receptors was assessed in 87 cases of IDC with contiguous areas of DCIS. Results showed that there was no difference in COX-2 expression comparing the in situ and invasive components of the tumors. In the in situ component, there was a statistically borderline increase in p53 expression in tumors that also expressed COX-2. ER-positive specimens were more common in the group of tumors that expressed COX-2 in the invasive component. From this study we conclude that the expression of COX-2 was similar in the in situ and invasive components of the breast carcinomas. COX-2 positivity was marginally related with the expression of p53 in the in situ components, and with the ER expression in the invasive components.}, } @article {pmid21679619, year = {2011}, author = {Kumano, H and Hozumi, Y and Shiozawa, M and Takehara, M and Koizumi, M and Sata, N and Lefor, AT and Yasuda, Y}, title = {Recurrent invasive ductal carcinoma of the breast presenting as a metastasis to the duodenum with long-term survival.}, journal = {The American surgeon}, volume = {77}, number = {6}, pages = {e107-8}, pmid = {21679619}, issn = {1555-9823}, mesh = {Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*secondary ; Duodenal Neoplasms/complications/*secondary/surgery ; Endoscopy, Gastrointestinal ; Female ; Humans ; Melena/etiology ; Middle Aged ; Neoplasm Recurrence, Local/*surgery ; Pancreaticoduodenectomy ; }, } @article {pmid21678409, year = {2012}, author = {Balestrieri, ML and Dicitore, A and Benevento, R and Di Maio, M and Santoriello, A and Canonico, S and Giordano, A and Stiuso, P}, title = {Interplay between membrane lipid peroxidation, transglutaminase activity, and cyclooxygenase 2 expression in the tissue adjoining to breast cancer.}, journal = {Journal of cellular physiology}, volume = {227}, number = {4}, pages = {1577-1582}, doi = {10.1002/jcp.22874}, pmid = {21678409}, issn = {1097-4652}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cyclooxygenase 2/*metabolism ; Disease Progression ; Female ; Fibroadenoma/metabolism/pathology ; GTP-Binding Proteins/*metabolism ; Humans ; Hyperplasia/metabolism/pathology ; Lipid Peroxidation ; Membrane Lipids/*metabolism ; Middle Aged ; Models, Biological ; Oxidative Stress ; Protein Glutamine gamma Glutamyltransferase 2 ; Reactive Oxygen Species/metabolism ; Transglutaminases/*metabolism ; Ubiquitin/metabolism ; }, abstract = {Breast cancer, a leading cause of cancer related deaths worldwide, is one of the most common neoplasms in women. The increased generation of reactive oxygen species (ROS) in breast lesion is critically involved in the mutagenic processes that drive to breast carcinoma initiation and progression. To date, the molecular events occurring in the tissue adjoin the cancer lesion have not been elucidated. Here, we investigated the role of excess ROS generation during human breast carcinogenesis by evaluating oxidative stress biomarkers, tissue transglutaminase (t-TGase) activity, and expression levels of ubiquitin and cyclooxygenase-2 (COX-2) in the normal tissue adjoin to fibroadenoma (nFA), atypical ductal hyperplasia (nADH), and invasive ductal carcinoma (nIDC) from 45 breast cancer patients. We found that lipid peroxidation and nitric oxide production significantly increased in nIDC respect to nFA and nADH (P < 0.005) whereas the 4-hydroxy-2-nonenal (HNE) protein-adducts increased only in nADH (P < 0.005). The increased lipid damage observed in nIDC correlates with estrogen receptor exposure in IDC (R(2) = 0.89). Moreover, nIDC and invasive ductal carcinoma (IDC) showed a 10-fold higher t-TGase activity compared to nFA and nADH. Contrary, COX-2 expression levels significantly decreased nIDC and IDC respect to the nFA and nADH (P < 0.001). The analysis of the free ubiquitin expression revealed equal levels in nADH and nIDC samples whereas high molecular weight-ubiquitin conjugate increased about fivefold only in nIDC (P < 0.01 vs. nADH). These novel findings reveal an interplay between membrane lipid peroxidation, t-TGase activity, and COX-2 expression levels in the tissue adjoining to neoplastic lesion during breast cancer progression.}, } @article {pmid21676924, year = {2011}, author = {Patani, N and Barbashina, V and Lambros, MB and Gauthier, A and Mansour, M and Mackay, A and Reis-Filho, JS}, title = {Direct evidence for concurrent morphological and genetic heterogeneity in an invasive ductal carcinoma of triple-negative phenotype.}, journal = {Journal of clinical pathology}, volume = {64}, number = {9}, pages = {822-828}, doi = {10.1136/jclinpath-2011-200135}, pmid = {21676924}, issn = {1472-4146}, support = {G1100450/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {Triple-negative breast cancers account for 12-17% of all invasive breast carcinomas and comprise a heterogeneous group of tumours, with varying histological features and clinical behaviours. Focal apocrine differentiation can be associated with a subset of these lesions. To establish whether morphological diversity is associated with divergent genetic aberrations the genomic profiles of microdissected, morphologically distinct components from an invasive ductal carcinoma of no special type with triple-negative phenotype and a region of apocrine differentiation were determined by high-resolution microarray-based comparative genomic hybridisation and validated by fluorescence in-situ hybridisation. Morphologically distinct components were found to harbour differing genetic aberrations, with the region of apocrine differentiation demonstrating genomic gains and losses on chromosome arms 9p and 9q, respectively, not present in non-apocrine areas. The results provide additional direct evidence of intra-tumour genetic heterogeneity in breast cancer and demonstrate that morphologically distinct regions can be associated with distinct genetic aberrations.}, } @article {pmid21667238, year = {2012}, author = {von Minckwitz, G and Darb-Esfahani, S and Loibl, S and Huober, J and Tesch, H and Solbach, C and Holms, F and Eidtmann, H and Dietrich, K and Just, M and Clemens, MR and Hanusch, C and Schrader, I and Henschen, S and Hoffmann, G and Tiemann, K and Diebold, K and Untch, M and Denkert, C}, title = {Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer--results from the GeparQuattro study (GBG 40).}, journal = {Breast cancer research and treatment}, volume = {132}, number = {3}, pages = {863-870}, doi = {10.1007/s10549-011-1621-0}, pmid = {21667238}, issn = {1573-7217}, mesh = {Adult ; Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/metabolism ; Clinical Trials, Phase III as Topic ; Cyclophosphamide/administration & dosage ; Deoxycytidine/administration & dosage/analogs & derivatives ; Docetaxel ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage/analogs & derivatives ; Humans ; Middle Aged ; Multivariate Analysis ; *Neoadjuvant Therapy ; Neoplasms, Multiple Primary/*drug therapy ; Receptor, ErbB-2/*metabolism ; Taxoids/administration & dosage ; Trastuzumab ; Treatment Outcome ; }, abstract = {Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2-0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.}, } @article {pmid21665471, year = {2011}, author = {Truin, W and Voogd, AC and Vreugdenhil, G and van der Sangen, MJ and van Beek, MW and Roumen, RM}, title = {Influence of histology on the effectiveness of adjuvant chemotherapy in patients with hormone receptor positive invasive breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {20}, number = {6}, pages = {505-509}, doi = {10.1016/j.breast.2011.05.005}, pmid = {21665471}, issn = {1532-3080}, mesh = {Aged ; Breast Neoplasms/*drug therapy/metabolism/mortality ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/mortality ; Carcinoma, Lobular/*drug therapy/metabolism/mortality ; *Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Netherlands ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Registries ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {INTRODUCTION: To investigate the effect of adjuvant chemotherapy on long term survival in addition to hormonal therapy in the systemic treatment of hormonal receptor positive breast cancer patients.

METHODS: All patients with primary non-metastatic hormonal receptor positive invasive lobular (mixed) (=ILC) and invasive ductal (=IDC) breast cancer operated on between 1986 and 2007 were identified from a population based cohort. Four hundred ninety-eight patients with lobular (mixed) and sixteen hundred seventeen with ductal cancer were eligible. Both groups were divided in patients receiving adjuvant hormonal treatment with or without systemic chemotherapy.

RESULTS: Overall survival was not statistically different in patients with ILC treated with adjuvant hormonal and chemotherapy compared to hormonal treatment alone (5-year survival 85.2% vs 82.8%, P = .68). In contrast, patients with IDC receiving adjuvant hormonal and chemotherapy had a significantly better overall survival compared to hormonal therapy alone (5-year survival rate 87.6% vs 80.8%, P < .001). In the multivariate analysis however, this significance disappeared suggesting that the data are possibly too small, too unbalanced, or influenced by other confounding factors to come to definitive conclusions.

CONCLUSIONS: There are good reasons to consider ductal and lobular breast cancers as different entities in future studies. Patients with hormone receptor positive ILC seem to benefit differently from additional adjuvant chemotherapy to hormonal therapy as compared with patients with IDC.}, } @article {pmid21663894, year = {2011}, author = {Mahjoub, S and Mehri, S and Ourda, F and Boussaada, R and Zouari, B and Ben Arab, S}, title = {[Epidemiological study of the idiopathic dilated cardiomyopathy in Tunisia].}, journal = {Annales de cardiologie et d'angeiologie}, volume = {60}, number = {4}, pages = {202-206}, doi = {10.1016/j.ancard.2011.04.006}, pmid = {21663894}, issn = {1768-3181}, mesh = {Adult ; Cardiomyopathy, Dilated/*epidemiology ; Female ; Humans ; Male ; Retrospective Studies ; Tunisia/epidemiology ; }, abstract = {AIMS OF THE STUDY: Idiopathic dilated cardiomyopathy (IDC) is a complex disease. The interest of this study were to investigate the epidemiology characteristics of the disease and to evaluate the prognostic echocardiographic markers by region in order to highlight the existence of genetic risk factors and/or environmental and to identify those patients who could benefit from early treatment and better care to avoid further complications of the disease.

PATIENTS AND METHODS: This is a retrospective study based on the Fischer exact and bilateral Mann-Whitney test.

RESULTS: We included 526 patients with dilated cardiomyopathies of them we detected 50 cases of IDC including 12 families: The average age was 39,3±15.2 years. The sex ratio was 2.6. Mean left ventricular end-diastolic diameter (DIVGd) was higher in patients from the North East region (44.3±6.2mm/m(2)). Using Receiver Operating Characteristics (ROC) curve, we found a threshold value of 40mm/m(2). The odds ratio associated with this cutoff was 9.2.

CONCLUSION: Our results suggest that the prevalence and severity of IDC were higher in the North East region of Tunisia. Furthermore, large-scale prospective studies are needed to confirm these findings. In confirmation of a higher prevalence, a genetic study should be undertaken in this region.}, } @article {pmid21658239, year = {2011}, author = {Abrhale, T and Brodie, A and Sabnis, G and Macedo, L and Tian, C and Yue, B and Serrero, G}, title = {GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells.}, journal = {BMC cancer}, volume = {11}, number = {}, pages = {231}, pmid = {21658239}, issn = {1471-2407}, support = {1R43CA124179-01/CA/NCI NIH HHS/United States ; 2R44CA124179-02/CA/NCI NIH HHS/United States ; }, mesh = {Aromatase/genetics/*metabolism ; Aromatase Inhibitors/*pharmacology ; Breast Neoplasms/*enzymology/genetics/physiopathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; Gene Silencing ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism/pharmacology ; Letrozole ; Nitriles/*pharmacology ; Progranulins ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; RNA, Small Interfering/metabolism ; Triazoles/*pharmacology ; }, abstract = {BACKGROUND: Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells

METHODS: We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.

RESULTS: GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.

CONCLUSION: Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.}, } @article {pmid21649468, year = {2011}, author = {Gupta, R and Babb, JS and Singh, B and Chiriboga, L and Liebes, L and Adams, S and Demaria, S}, title = {The numbers of FoxP3+ lymphocytes in sentinel lymph nodes of breast cancer patients correlate with primary tumor size but not nodal status.}, journal = {Cancer investigation}, volume = {29}, number = {6}, pages = {419-425}, pmid = {21649468}, issn = {1532-4192}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; 5P30CA016087-31/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/immunology/*pathology ; Female ; Forkhead Transcription Factors/*analysis ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Sentinel Lymph Node Biopsy ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells, lymphocytes marked by expression of the transcription factor Forkhead Box Protein P3 (FoxP3), inhibit the activation of tumor-specific T cells in tumor-draining lymph nodes. Immunohistochemical analyses of sentinel lymph nodes (SLNs) from 104 breast cancer patients showed a significant association (p = .0028, Pearson correlation) between the number of FoxP3+ cells and the size of primary breast invasive ductal carcinoma. In contrast, there was no correlation between the number of FoxP3+ cells and the presence of SLN metastases, or other clinicopathological parameters. These results suggest the presence of an immune suppressive environment in SLNs of larger tumors.}, } @article {pmid21645409, year = {2011}, author = {Zhang, Y and Zhu, J and Tang, Y and Li, F and Zhou, H and Peng, B and Zhou, C and Fu, R}, title = {X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {49}, pmid = {21645409}, issn = {1746-1596}, mesh = {Apoptosis ; Apoptosis Regulatory Proteins ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnosis/metabolism/mortality/therapy ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/mortality/therapy ; Cell Nucleus/metabolism/*pathology ; Combined Modality Therapy ; Cytoplasm/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/metabolism ; Kaplan-Meier Estimate ; Mastectomy, Modified Radical ; Mitochondrial Proteins/metabolism ; Prognosis ; Survival Rate ; X-Linked Inhibitor of Apoptosis Protein/*metabolism ; }, abstract = {BACKGROUND: It's well recognized that X-linked inhibitor of apoptosis (XIAP) was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac) was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC) were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI), clinicopathologic parameters and prognosis in IDC.

METHODS: Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot.

RESULTS: Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (P<0.0001). It was noteworthy that 44 cases of IDC were positive in nuclear for XIAP, but none was for Smac. Expression status of Smac was more prevalent in HER2 positive group than negative group (P<0.0001) and AI was positively correlated with HER2 protein expression (rs=0.265, P=0.017). The present study first revealed that XIAP positive nuclear labeling (XIAP-N), but not cytoplasmic staining (XIAP-C), was the apoptotic marker correlated significantly with patients' shortened overall survival (P=0.039). Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status.

CONCLUSION: Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.}, } @article {pmid21641801, year = {2011}, author = {Pantanowitz, L and Sen, S and Crisi, GM and Makari-Judson, G and Garb, J and Skiest, D}, title = {Spectrum of breast disease encountered in HIV-positive patients at a community teaching hospital.}, journal = {Breast (Edinburgh, Scotland)}, volume = {20}, number = {4}, pages = {303-308}, doi = {10.1016/j.breast.2010.08.003}, pmid = {21641801}, issn = {1532-3080}, mesh = {AIDS-Related Opportunistic Infections/diagnosis/*epidemiology ; Adult ; Breast Diseases/diagnosis/*epidemiology ; Breast Neoplasms/diagnosis/epidemiology ; Comorbidity ; Female ; Gynecomastia/epidemiology ; HIV Seropositivity/*epidemiology ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; *Severity of Illness Index ; }, abstract = {INTRODUCTION: HIV infection directly and indirectly affects breast tissue. This study describes the spectrum of HIV-related breast disease encountered at a community teaching hospital.

METHODS: A 9 year retrospective review was performed of HIV-positive patients with a breast-related diagnosis seen at our institution. Patient demographics, HIV status, comorbid disease, medications, clinical findings, diagnostic procedure, pathology, treatment and outcome were recorded.

RESULTS: A total of 46 individuals were included with a median age of 47 years (range 24-64 years) and male:female ratio of 1:3 (12 men and 34 women). Mean duration of HIV infection was 7 years during which time 46% of patients had an AIDS defining illness. Median CD4 cell count was 437 cells/mm(3) (range 2 to ≥500 cells/mm(3)) at the time of the breast diagnosis. Breast disease identified included benign conditions (59% total: 92% for men, 47% for women), infection (17% total: 8% for men, 21% for women), cancer (22% total: 0% for men, 29% for women), and atypia (2% total: 0% for men, 3% for women). Patients with a breast infection had a lower median CD4 cell count than those with breast cancer or benign conditions. Gynecomastia was detected in seven out of 12 (58%) men. In these men, antiretroviral therapy (ART) of all drug classes was associated with gynecomastia. Breast cancer occurred only in women and included patients with invasive ductal carcinoma (n = 7), ductal carcinoma in situ (n = 2), and liposarcoma diagnosed in one individual. Specific risk factors for breast cancer in this setting were not identified. Five (11%) patients died, only one from breast disease during the study period.

CONCLUSION: These data indicate that increased longevity in patients with chronic HIV infection may be associated with the occurrence of breast conditions in both men and women. A broad spectrum of breast disease should be anticipated in HIV-infected persons living longer with effective ART.}, } @article {pmid21640491, year = {2011}, author = {Shah, C and Wilkinson, JB and Shaitelman, S and Grills, I and Wallace, M and Mitchell, C and Vicini, F}, title = {Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma.}, journal = {International journal of radiation oncology, biology, physics}, volume = {81}, number = {4}, pages = {e547-51}, doi = {10.1016/j.ijrobp.2011.04.050}, pmid = {21640491}, issn = {1879-355X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/drug therapy/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/chemistry/drug therapy/mortality/pathology/radiotherapy ; Carcinoma, Lobular/chemistry/drug therapy/mortality/pathology/*radiotherapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Radiotherapy/methods ; Treatment Outcome ; Tumor Burden ; }, abstract = {PURPOSE: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI).

METHODS AND MATERIALS: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed.

RESULTS: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients.

CONCLUSION: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.}, } @article {pmid21632715, year = {2011}, author = {Harden, JL and Gu, T and Kilinc, MO and Rowswell-Turner, RB and Virtuoso, LP and Egilmez, NK}, title = {Dichotomous effects of IFN-γ on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {187}, number = {1}, pages = {126-132}, pmid = {21632715}, issn = {1550-6606}, support = {R01 CA100656/CA/NCI NIH HHS/United States ; R01 CA100656-06/CA/NCI NIH HHS/United States ; R01-CA100656/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Movement/genetics/immunology ; Coculture Techniques ; Dendritic Cells/*immunology/metabolism/*pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage/physiology ; Immune Tolerance/genetics ; Interferon-gamma/deficiency/genetics/*physiology ; Interleukin-12/*administration & dosage/physiology ; Lung Neoplasms/immunology/pathology/prevention & control ; Lymph Nodes/immunology/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mice, Transgenic ; Pulmonary Alveoli/immunology/metabolism/pathology ; T-Lymphocyte Subsets/*immunology/metabolism/*pathology ; Tumor Escape/genetics/*immunology ; }, abstract = {Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF-treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24-48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8(+) T cells but preferentially induced CD4(+)Foxp3(+) T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12-mediated antitumor T cell immunity.}, } @article {pmid21632555, year = {2011}, author = {O'Toole, SA and Machalek, DA and Shearer, RF and Millar, EK and Nair, R and Schofield, P and McLeod, D and Cooper, CL and McNeil, CM and McFarland, A and Nguyen, A and Ormandy, CJ and Qiu, MR and Rabinovich, B and Martelotto, LG and Vu, D and Hannigan, GE and Musgrove, EA and Christ, D and Sutherland, RL and Watkins, DN and Swarbrick, A}, title = {Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer.}, journal = {Cancer research}, volume = {71}, number = {11}, pages = {4002-4014}, doi = {10.1158/0008-5472.CAN-10-3738}, pmid = {21632555}, issn = {1538-7445}, mesh = {Animals ; Breast Neoplasms/*metabolism/*pathology ; Cell Line, Tumor ; Cohort Studies ; Disease Models, Animal ; Disease Progression ; Female ; Hedgehog Proteins/*biosynthesis ; Humans ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Prognosis ; Signal Transduction ; Stromal Cells/metabolism/pathology ; }, abstract = {Hedgehog (Hh) signaling plays an important role in several malignancies but its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma of the breast, expression of Hh ligand was significantly associated with increased risk of metastasis, breast cancer-specific death, and a basal-like phenotype. A paracrine signature, encompassing high epithelial Hh ligand and high stromal Gli1, was an independent predictor for overall survival in multivariate analysis. In 2 independent histological progression series (n = 301), Hh expression increased with atypia. Hh ligand overexpression in a mouse model of basal breast cancer increased growth, induced a poorly differentiated phenotype, accelerated metastasis, and reduced survival. A stromal requirement for these effects was supported by the lack of similar Hh-mediated changes in vitro, and by stromal-specific expression of Hh target genes in vivo. Furthermore, inhibition of Hh ligand with a monoclonal antibody (5E1) inhibited tumor growth and metastasis. These data suggest that epithelial-stromal Hh signaling, driven by ligand expression in carcinoma cells, promotes breast cancer growth and metastasis. Blockade of Hh signaling to peritumoral stromal cells may represent a novel therapeutic approach in some basal-like breast cancers.}, } @article {pmid21631268, year = {2011}, author = {Bai, S and Wang, D and Klein, MJ and Siegal, GP}, title = {Characterization of CXCR4 expression in chondrosarcoma of bone.}, journal = {Archives of pathology & laboratory medicine}, volume = {135}, number = {6}, pages = {753-758}, doi = {10.5858/2009-0230-OA.1}, pmid = {21631268}, issn = {1543-2165}, support = {AR 046031/AR/NIAMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Bone Neoplasms/diagnosis/*metabolism ; Chondrosarcoma/diagnosis/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Receptors, CXCR4/*metabolism ; Young Adult ; }, abstract = {CONTEXT: Alterations in molecular elements derived from the CXC chemokine receptor 4 (CXCR4)/stromal-derived factor 1 (SDF-1) cytokine system have been found to strongly correlate with neoplastic progression leading to metastasis in a number of tumors, including osteosarcoma. Excluding hematologic malignancies, chondrosarcoma of bone is the most common primary malignant tumor of bone in adults in the United States. Like osteosarcoma, chondrosarcoma preferentially metastasizes to lung, bone, and very rarely to regional lymph nodes. However, the role of the signal pathway(s) driving neoplastic progression in chondrosarcoma has not yet been clearly elucidated.

OBJECTIVE: To test whether CXCR4 was detectable in chondrosarcoma and whether CXCR4 expression levels correlated with chondrosarcoma grade.

DESIGN: Twenty-two chondrosarcoma samples banked at our institution between 2001 and 2006 were retrieved for study. By using invasive ductal carcinoma of the breast and osteosarcoma as the positive controls, immunohistochemistry was performed on paraffin-embedded tissue sections and the intensity of the tumor cells was analyzed by morphometric techniques.

RESULTS: All chondrosarcoma cases (22 of 22) were immunoreactive for CXCR4. However, the staining intensity of the CXCR4 between the low- and high-grade groups was significantly different. There was a higher staining intensity in high-grade chondrosarcoma cells (P < .001).

CONCLUSION: CXCR4 is expressed in chondrosarcomas. CXCR4 expression levels were higher in high-grade chondrosarcoma cells than in low-grade specimens. A larger number of cases will be required to confirm these results and expand the observation, but preliminary data would argue for CXCR4 immunohistochemistry as a potential marker for biologic aggressiveness in chondrosarcoma of bone.}, } @article {pmid21617713, year = {2011}, author = {Wang, X and Yi, L and Zhu, Y and Zou, J and Hong, Y and Zheng, W}, title = {AKT signaling pathway in invasive ductal carcinoma of the breast: correlation with ERa, ERβ and HER-2 expression.}, journal = {Tumori}, volume = {97}, number = {2}, pages = {185-190}, doi = {10.1177/030089161109700209}, pmid = {21617713}, issn = {0300-8916}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Disease-Free Survival ; Estrogen Receptor alpha/*metabolism ; Estrogen Receptor beta/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptor, ErbB-2/*metabolism ; *Signal Transduction ; }, abstract = {AIMS AND BACKGROUND: Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ERβ expression is a useful biomarker for breast cancer in a manner that is independent of ERa expression. However, studies evaluating ERβ expression with certain tumor variables, such as tumor grade and disease-free survival, had produced conflicting results. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. The current study attempted to compare the relative associations of variables including ERa, ERβ, HER-2/neu and AKT staining with the presence of metastases or survival.

METHODS AND STUDY DESIGN: Immunohistochemical staining was employed to determine the expression of ERa, ERβ, pAkt and HER-2/neu in 110 cases of primary breast carcinoma.

RESULTS: Positive ERa, ERβ, pAkt and HER-2/neu expressions were respectively observed in 46.4% (51/110), 59.1% (65/110), 40.9% (45/110) and 31.8% (35/110) of the tumors. pAkt was significantly associated with HER-2/neu overexpression (P <0.005) and axillary lymph node metastasis (P <0.05). However, there was no significant relationship between pAkt and ERa, ERβ, p53 (P >0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients.

CONCLUSIONS: The current study suggested that activity of the Akt signaling pathway may indicate a poor prognosis in patients with breast carcinoma. The results implied that estrogen can activate the PI3K-Akt pathway through ERa and ERβ-independent mechanisms in breast cancer.}, } @article {pmid21591007, year = {2011}, author = {Jansen, SA and Shimauchi, A and Zak, L and Fan, X and Karczmar, GS and Newstead, GM}, title = {The diverse pathology and kinetics of mass, nonmass, and focus enhancement on MR imaging of the breast.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {33}, number = {6}, pages = {1382-1389}, pmid = {21591007}, issn = {1522-2586}, support = {P50 CA125183/CA/NCI NIH HHS/United States ; P50 CA125183-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/diagnosis/pathology ; Contrast Media/*pharmacology ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Kinetics ; Magnetic Resonance Imaging/*methods ; Middle Aged ; ROC Curve ; Reproducibility of Results ; }, abstract = {PURPOSE: To compare the pathology and kinetic characteristics of breast lesions with focus-, mass-, and nonmass-like enhancement.

MATERIALS AND METHODS: A total of 852 MRI detected breast lesions in 697 patients were selected for an IRB approved review. Patients underwent dynamic contrast enhanced MRI using one pre- and three to six postcontrast T(1)-weighted images. The "type" of enhancement was classified as mass, nonmass, or focus, and kinetic curves quantified by the initial enhancement percentage (E(1)), time to peak enhancement (T(peak)), and signal enhancement ratio (SER). These kinetic parameters were compared between malignant and benign lesions within each morphologic type.

RESULTS: A total of 552 lesions were classified as mass (396 malignant, 156 benign), 261 as nonmass (212 malignant, 49 benign), and 39 as focus (9 malignant, 30 benign). The most common pathology of malignant/benign lesions by morphology: for mass, invasive ductal carcinoma/fibroadenoma; for nonmass, ductal carcinoma in situ (DCIS)/fibrocystic change(FCC); for focus, DCIS/FCC. Benign mass lesions exhibited significantly lower E(1), longer T(peak), and lower SER compared with malignant mass lesions (P < 0.0001). Benign nonmass lesions exhibited only a lower SER compared with malignant nonmass lesions (P < 0.01).

CONCLUSION: By considering the diverse pathology and kinetic characteristics of different lesion morphologies, diagnostic accuracy may be improved.}, } @article {pmid21584795, year = {2011}, author = {Koo, JS and Park, S and Kim, SI and Lee, S and Park, BW}, title = {The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {32}, number = {4}, pages = {787-799}, pmid = {21584795}, issn = {1423-0380}, mesh = {Adult ; Biomarkers, Tumor/*analysis/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/pathology ; Caveolin 1/*biosynthesis ; Caveolins/biosynthesis ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Platelet-Derived Growth Factor/biosynthesis ; Prognosis ; Tissue Array Analysis ; Tumor Microenvironment/*physiology ; }, abstract = {We aimed to investigate the expression of caveolin-1, -2, -3, and platelet-derived growth factor (PDGF) β receptor in breast cancer cells and stroma by immunohistochemistry and to analyze their implications. The expression rates of stromal caveolin-2 and PDGF β receptor increased as the tumor progressed from ductal carcinoma in situ to microinvasive ductal carcinoma, intraductal component of invasive ductal carcinoma (IDC), and IDC (p<0.001). The expression loss of caveolin-1 in tumor stroma of IDC correlated with high tumor stage (p<0.001), high nodal stage (p=0.011), high cancer stage (p=0.005), estrogen receptor negativity (p=0.003), and tumor recurrence (p=0.003). In addition, the expression loss of caveolin-1 in tumor stroma was correlated with a shorter disease-free survival and an overall survival (p<0.001). In conclusion, the loss of stromal caveolin-1 is related to poor prognosis in IDC.}, } @article {pmid21575109, year = {2011}, author = {Teramoto, N and Tanimizu, M}, title = {Validation analysis of Japanese histological classification of breast cancer using the National Summary of Hospital Cancer Registry 2007, Japan.}, journal = {Cancer science}, volume = {102}, number = {8}, pages = {1597-1601}, doi = {10.1111/j.1349-7006.2011.01984.x}, pmid = {21575109}, issn = {1349-7006}, mesh = {Breast Neoplasms/*classification/*pathology ; Female ; Hospitals ; Humans ; Japan ; Lymphatic Metastasis ; Registries ; Time Factors ; }, abstract = {Using the National Summary of Hospital Cancer Registry 2007, Japan, (HCRJ) from 219 local core cancer hospitals (LCCH) that had registered more than 29 breast cancers, we validated the Japanese classification of breast cancer (JCBC). In JCBC, most invasive ductal carcinomas (IDC) are subclassified as papillotubular carcinoma (coded as 850031 in the HCRJ) or scirrhous carcinoma (850033). Because of the confusing criterion that IDC with substantial ductal carcinoma in situ (DCIS) is papillotubular carcinoma, pathological T (pT)1 might be overestimated as pT2-3 by measuring the tumor size to include DCIS at LCCH where papillotubular carcinoma is diagnosed correctly. The LCCH were divided based on the difference between the proportion of papillotubular carcinoma to scirrhous carcinoma (PPS), that is, the proportion of 850031 cases to the sum of 850031 and 850033 cases at each LCCH (mean: 45.6%), and the PPS of the LCCH whose in-house histological classification was the origin of JCBC (standard PPS [StPPS]: 42.3%), into G5 (PPS within StPPS ± 5%), L5 (PPS < StPPS-5%), HL (StPPS + 15% ≥ PPS > StPPS + 5%), and HH (PPS > StPPS + 15%). On pT2-3, the proportion of N1-3 cases to N0 in G5 and HL was significantly lower than that in L5. The averages of the proportion at each LCCH of G5 and HL were also significantly lower than that of L5. Meanwhile, on pT1, the proportions and averages were not significantly different among the groups. The frequent overestimation of pT in G5 and HL explains their lower frequency of lymph nodal metastasis on pT2-3, leaving the frequency on pT1 unchanged. The JCBC has spoiled the accuracy of pTNM.}, } @article {pmid21569821, year = {2011}, author = {Tucci, M and Ciavarella, S and Strippoli, S and Brunetti, O and Dammacco, F and Silvestris, F}, title = {Immature dendritic cells from patients with multiple myeloma are prone to osteoclast differentiation in vitro.}, journal = {Experimental hematology}, volume = {39}, number = {7}, pages = {773-83.e1}, doi = {10.1016/j.exphem.2011.04.006}, pmid = {21569821}, issn = {1873-2399}, mesh = {Bone Marrow Cells/immunology/metabolism/pathology ; Cell Differentiation/*immunology ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/immunology/metabolism ; Coculture Techniques ; Dendritic Cells/*immunology/metabolism/pathology ; Flow Cytometry ; Humans ; Immunohistochemistry ; Multiple Myeloma/*immunology/metabolism/pathology ; Osteoclasts/*immunology/metabolism ; RANK Ligand/immunology/metabolism ; Receptors, CXCR4/immunology/metabolism ; Receptors, Chemokine/genetics/immunology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transmembrane Activator and CAML Interactor Protein/immunology/metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor Ligand Superfamily Member 13/immunology/metabolism ; }, abstract = {OBJECTIVE: Recent studies demonstrated that the interactions of immature dendritic cells (iDCs) with myeloma cells enhance the clonogenic capacity of tumor cells while iDCs undergo osteoclast (OC) transformation. Here, we investigated these interactions as well as iDC behavior in terms of both migration and OC differentiation.

MATERIALS AND METHODS: We studied 12 patients with multiple myeloma (MM) and 5 with monoclonal gammopathy of undetermined significance. Chemokine receptors, tumor-mediated chemotaxis, and a proliferation-inducing ligand (APRIL) expression were investigated in iDCs, whereas receptor activator of nuclear factor κB ligand (RANKL) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) levels were measured in primary plasma cells. Furthermore, cocultures of myeloma cells with autologous iDCs were installed to verify OC differentiation of these cells. Finally, the role of RANK/RANKL in such OC differentiation was investigated by inhibiting this molecular pathway.

RESULTS: Peripheral and marrow iDCs from MM showed high CXCR4 expression and were augmented in bone marrow of MM patients with respect to monoclonal gammopathy of undetermined significance. Also, iDCs expressed APRIL, whereas RANKL and TACI were upregulated by malignant cells. The cellular contact of myeloma cells with iDCs enhanced the clonogenic effect on tumor growth, whereas iDCs were directly primed to undergo OC transformation. These iDCs, indeed, exerted typical bone resorption that was abrogated by disabling the RANK/RANKL pathway signals. By contrast, plasma cells from monoclonal gammopathy of undetermined significance patients were ineffective in transforming autologous iDCs.

CONCLUSIONS: Our results emphasize the marrow cross-talk of iDCs with myeloma cells as an additional mechanism that upregulates osteoclastogenesis in MM, and suggest that such a RANKL-mediated OC differentiation of iDCs observed in vitro may also occur in vivo.}, } @article {pmid21567184, year = {2012}, author = {Shin, SJ and Jung, M and Jeung, HC and Kim, HR and Rha, SY and Roh, JK and Chung, HC and Ahn, JB}, title = {A phase I pharmacokinetic study of TSU-68 (a multiple tyrosine kinase inhibitor of VEGFR-2, FGF and PDFG) in combination with S-1 and oxaliplatin in metastatic colorectal cancer patients previously treated with chemotherapy.}, journal = {Investigational new drugs}, volume = {30}, number = {4}, pages = {1501-1510}, pmid = {21567184}, issn = {1573-0646}, mesh = {Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/pharmacokinetics/*therapeutic use ; Colorectal Neoplasms/blood/*drug therapy/pathology ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; Fibroblast Growth Factors/antagonists & inhibitors/metabolism ; Humans ; Indoles/administration & dosage/adverse effects/*pharmacokinetics/*therapeutic use ; Male ; Middle Aged ; Neoplasm Metastasis ; Organoplatinum Compounds/administration & dosage/adverse effects/*therapeutic use ; Oxaliplatin ; Oxindoles ; Oxonic Acid/administration & dosage/adverse effects/*therapeutic use ; Platelet-Derived Growth Factor/antagonists & inhibitors/metabolism ; Propionates/administration & dosage/adverse effects/*pharmacokinetics/*therapeutic use ; Protein Kinase Inhibitors/administration & dosage/adverse effects/*pharmacokinetics/therapeutic use ; Pyrroles ; Tegafur/administration & dosage/adverse effects/*therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/metabolism ; }, abstract = {TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. We conducted a phase I study to evaluate the safety and pharmacokinetic of TSU-68 when used with S-1 and oxaliplatin (SOX) in metastatic colorectal cancer (mCRC) patients. Patients with mCRC were treated with TSU-68 200 mg (Level 1) or 400 mg (Level 2) b.i.d. daily, S-1 35 mg/m(2) b.i.d. on Days 1-14 and oxaliplatin 130 mg/m(2) i.v. on Day 1 repeatedly every 3 weeks. Of eleven patients enrolled, two patients were excluded from dose limiting toxicity (DLT) assessment. Six patients at Level 1 experienced no DLT. Of three patients at Level 2, two patients experienced DLTs (one patient: grade 3 hiccup and palmar-plantar erythrodysaesthesia syndrome, another one: grade 2 neutropenia which prevented the initiation of next cycle within 14 days). The maximal tolerated dose (MTD) and recommended dose (RD) of TSU-68 was 200 mg b.i.d. C(max) and AUC(0-t) of TSU-68 at Level 2 were higher than those at Level 1, but doubling the dose of TSU-68 increased C(max) and AUC(0-t) less than two-fold. There was no appreciable difference in the PK of S-1 components (FT, CDHP and Oxo), 5-FU and oxaliplatin-derived platinum between Levels 1 and 2. A significant decrease in PDGF after TSU-68 treatment was identified and it might serve as pharmacodynamic marker of TSU-68. Administration of TSU-68 in combination with SOX is generally well tolerated. The MTD and RD of TSU-68 in this study was 200 mg b.i.d. daily.}, } @article {pmid21565889, year = {2011}, author = {Ventrella, V and Tufaro, A and Zito, FA and Addante, M and Stea, B and Dentamaro, R and D'Amico, C and Paradiso, A}, title = {Mammographic characteristics and vacuum-assisted breast biopsy (VABB) of non-palpable breast lesions.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {52}, number = {6}, pages = {602-607}, doi = {10.1258/ar.2011.100319}, pmid = {21565889}, issn = {1600-0455}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle/*methods ; Breast Neoplasms/diagnostic imaging/*pathology ; Calcinosis/diagnostic imaging/pathology ; Chi-Square Distribution ; Diagnosis, Differential ; Early Diagnosis ; Female ; Humans ; Logistic Models ; Mammography ; Middle Aged ; Palpation ; Predictive Value of Tests ; Retreatment/statistics & numerical data ; Vacuum ; }, abstract = {BACKGROUND: The new imaging technology made available today allows for an early detection of small subclinical breast lesions which frequently call for guided presurgical micro-histology.

PURPOSE: To evaluate the relationship between vacuum-assisted breast biopsy (VABB) histopathological diagnoses and mammographic findings in non-palpable breast lesions.

MATERIAL AND METHODS: The breast lesions of 1393 women who had received consecutive screening mammograms between 2001 and 2007 were assessed by VABB. The mammographic breast lesions, classified according to the Breast Imaging Reporting and Data System (BI-RADS), were subjected to VABB only if rated as highly suspicious (2%), suspicious (64.5%) for malignancy, or probably benign (33.5%).

RESULTS: VABB findings included 981 (70.5%) probably benign lesions, 407 (29.2%) suspicious/malignant lesions, and five (0.3%) cases which were considered as inappropriate for diagnostic purposes. At histology, 10.2% of the suspicious/malignant lesions were classified as proliferative lesions, 11.1% as ductal carcinoma in situ (DCIS), and 8% as invasive ductal carcinoma (IDC). The positive predictive value (PPV) of BI-RADS assessment categories 3, 4 and 5 was 4.1%, 25.3% and 75%, respectively. The occurrence of obscured or spiculated masses was found to exhibit the highest PPV for malignancy (12.5% in BI-RADS 3 and 63% in BI-RADS 4), followed by microcalcifications which showed a malignancy rate of 6.4% in BI-RADS 3, and 20% in BI-RADS 4.

CONCLUSION: VABB turns out to be effective in the assessment of many malignant and benign preclinical tumour lesions thus allowing for a significant reduction of the number of surgical biopsies.}, } @article {pmid21559090, year = {2011}, author = {Wang, Y and Wang, L and Chen, Y and Li, L and Yang, X and Li, B and Song, S and Yang, L and Hao, Y and Yang, J}, title = {ER81 Expression in Breast Cancers and Hyperplasia.}, journal = {Pathology research international}, volume = {2011}, number = {}, pages = {980513}, pmid = {21559090}, issn = {2042-003X}, abstract = {ER81 is a transcription factor that may contribute to breast cancer; however, little known about the role of ER81 in breast carcinogenesis. To investigate the role of ER81 in breast carcinogenesis, we examined ER81 expression in IDC, DCIS, ADH, HUT, and normal breast tissues by immunohistochemical staining. We found that ER81 overexpression was detected in 25.7% (9/35) of HUT, 41.2% (7/17) of ADH, 54.5% (12/22) of DCIS, and 63.0% (51/81) of IDC. In 20 of breast cancer tissues combined with DCIS, ADH, and HUT, ER81 expression was found in 14/20 (70%) IDC. In these 14 cases all cases were ER81 positive expression in DCIS, 13 of 14 cases were positively expressed of ER81 in ADH and 8 of 14 were positive for ER81 in HUT components. A statistical significance was found between NBT and HUT (P < .05) and HUT and ADH (P < .05). Clinical-pathological features analysis of breast cancer revealed that ER81 expression was significantly associated with Her2 amplification and was negatively associated with ER and PR expression. Our results demonstrated that ER81 overexpression was present in the early stage of breast development that suggested that ER81 overexpression may play an important role in breast carcinogenesis.}, } @article {pmid21558492, year = {2011}, author = {Foth, BJ and Zhang, N and Chaal, BK and Sze, SK and Preiser, PR and Bozdech, Z}, title = {Quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum.}, journal = {Molecular & cellular proteomics : MCP}, volume = {10}, number = {8}, pages = {M110.006411}, pmid = {21558492}, issn = {1535-9484}, mesh = {Aryldialkylphosphatase/genetics/metabolism ; Catalase/genetics/metabolism ; Cell Culture Techniques ; Erythrocytes/enzymology/metabolism/*parasitology ; *Host-Parasite Interactions ; Humans ; Lactoferrin/genetics/metabolism ; Malaria, Falciparum/*metabolism/parasitology ; Models, Biological ; Oxidoreductases Acting on CH-CH Group Donors/genetics/metabolism ; Plasmodium falciparum/growth & development/metabolism/*physiology ; Protein Isoforms/genetics/metabolism ; Proteome/genetics/metabolism ; Protozoan Proteins/genetics/*metabolism ; Spores, Protozoan/metabolism ; Superoxide Dismutase/genetics/metabolism ; Superoxide Dismutase-1 ; Transcription, Genetic ; }, abstract = {Studies of the Plasmodium falciparum transcriptome have shown that the tightly controlled progression of the parasite through the intra-erythrocytic developmental cycle (IDC) is accompanied by a continuous gene expression cascade in which most expressed genes exhibit a single transcriptional peak. Because the biochemical and cellular functions of most genes are mediated by the encoded proteins, understanding the relationship between mRNA and protein levels is crucial for inferring biological activity from transcriptional gene expression data. Although studies on other organisms show that <50% of protein abundance variation may be attributable to corresponding mRNA levels, the situation in Plasmodium is further complicated by the dynamic nature of the cyclic gene expression cascade. In this study, we simultaneously determined mRNA and protein abundance profiles for P. falciparum parasites during the IDC at 2-hour resolution based on oligonucleotide microarrays and two-dimensional differential gel electrophoresis protein gels. We find that most proteins are represented by more than one isoform, presumably because of post-translational modifications. Like transcripts, most proteins exhibit cyclic abundance profiles with one peak during the IDC, whereas the presence of functionally related proteins is highly correlated. In contrast, the abundance of most parasite proteins peaks significantly later (median 11 h) than the corresponding transcripts and often decreases slowly in the second half of the IDC. Computational modeling indicates that the considerable and varied incongruence between transcript and protein abundance may largely be caused by the dynamics of translation and protein degradation. Furthermore, we present cyclic abundance profiles also for parasite-associated human proteins and confirm the presence of five human proteins with a potential role in antioxidant defense within the parasites. Together, our data provide fundamental insights into transcript-protein relationships in P. falciparum that are important for the correct interpretation of transcriptional data and that may facilitate the improvement and development of malaria diagnostics and drug therapy.}, } @article {pmid21557333, year = {2011}, author = {Ismail, HM and Medhat, AM and Karim, AM and Zakhary, NI}, title = {FHIT gene and flanking region on chromosome 3p are subjected to extensive allelic loss in Egyptian breast cancer patients.}, journal = {Molecular carcinogenesis}, volume = {50}, number = {8}, pages = {625-634}, doi = {10.1002/mc.20797}, pmid = {21557333}, issn = {1098-2744}, mesh = {Acid Anhydride Hydrolases/*genetics ; Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosomes, Human, Pair 3 ; Egypt ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; *Loss of Heterozygosity ; Microsatellite Repeats ; Middle Aged ; Neoplasm Proteins/*genetics ; }, abstract = {The fragile histidine triad gene (FHIT) is a candidate tumor suppressor gene at chromosome 3p14.2. Deletions in FHIT gene were reported in different types of cancer including breast cancer. In this study, we investigated the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in cancerous and pre-neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the pre-neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal carcinoma (IDC) histopathological type while no association observed between LOH and patients' age, tumor grade, or lymph node involvement. We also investigated FHIT gene expression profiles in breast cancer using Oncomine database. We found that FHIT is significantly reduced in all investigated studies. We conclude that, FHIT is underexpressed in breast cancer tissues compared to their normal counterparts due to the extensive allelic loss that is observed in its gene structure.}, } @article {pmid21556773, year = {2012}, author = {Jin, B and Luo, XP and Ni, HC and Shen, W and Shi, HM and Li, Y}, title = {A meta-analysis of HLA-DR polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.}, journal = {Molecular biology reports}, volume = {39}, number = {1}, pages = {221-226}, pmid = {21556773}, issn = {1573-4978}, mesh = {Cardiomyopathy, Dilated/*genetics ; Case-Control Studies ; Genetic Association Studies ; Genetic Predisposition to Disease/*genetics ; HLA-DR Antigens/*genetics ; Humans ; Polymorphism, Genetic/*genetics ; Sensitivity and Specificity ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR polymorphism and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 19 case-control studies including 1,378 cases and 10,383 controls provided data on the association between HLA-DR polymorphism and genetic susceptibility to IDC. Overall, statistically elevated frequencies of HLA-DR4 (OR 1.58; 95% CI 1.21-2.07; P=0.0009) and HLA-DR5 (OR 1.35; 95% CI 1.05-1.73; P=0.02) alleles were found in patients with IDC compared with controls. Individuals with HLA-DR3 antigen have a protective effect against IDC (OR 0.72; 95% CI 0.58-0.90; P=0.004). In summary, this meta-analysis indicated that certain HLA-DR alleles may be genetic markers for susceptibility and resistance to IDC.}, } @article {pmid21555521, year = {2011}, author = {Li, X and Wen, W and Liu, K and Zhu, F and Malakhova, M and Peng, C and Li, T and Kim, HG and Ma, W and Cho, YY and Bode, AM and Dong, Z and Dong, Z}, title = {Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines.}, journal = {The Journal of biological chemistry}, volume = {286}, number = {25}, pages = {22291-22299}, pmid = {21555521}, issn = {1083-351X}, support = {CA120388/CA/NCI NIH HHS/United States ; R01 CA077646/CA/NCI NIH HHS/United States ; R37 CA081064/CA/NCI NIH HHS/United States ; CA077646/CA/NCI NIH HHS/United States ; R01 CA120388/CA/NCI NIH HHS/United States ; ES016548/ES/NIEHS NIH HHS/United States ; R01 ES016548/ES/NIEHS NIH HHS/United States ; CAR37CA081064//PHS HHS/United States ; }, mesh = {Amino Acid Sequence ; Antineoplastic Agents/*pharmacology/therapeutic use ; Apoptosis/*drug effects/genetics ; Base Sequence ; Breast Neoplasms/drug therapy/enzymology/metabolism/*pathology ; Carcinoma, Ductal/drug therapy/enzymology/metabolism/pathology ; Caspase 7/chemistry/*metabolism ; Cell Line, Tumor ; *Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Phosphorylation/drug effects ; Protein Transport ; p21-Activated Kinases/deficiency/genetics/*metabolism ; }, abstract = {p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in resistance to chemotherapy is unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with a human non-tumorigenic mammary epithelial cell line and adjacent normal breast tissue, respectively. Interestingly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at the Ser-30, Thr-173, and Ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapeutic resistance in human breast invasive ductal carcinoma by negatively regulating caspase-7 activity.}, } @article {pmid21547576, year = {2011}, author = {Moelans, CB and de Wegers, RA and Monsuurs, HN and Maess, AH and van Diest, PJ}, title = {Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study.}, journal = {Cellular oncology (Dordrecht)}, volume = {34}, number = {5}, pages = {475-482}, pmid = {21547576}, issn = {2211-3436}, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown.

METHODS: In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.

RESULTS: There were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p = 0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high grade IDC was similar, and although EGFR alterations were exclusively found in high grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.

CONCLUSION: In conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high grade DCIS showed more copy number changes than low/intermediate grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high grade DCIS specific genes may be potential targets for treatment and/or predict progression.}, } @article {pmid21545433, year = {2011}, author = {Han, JS and Molberg, KH and Sarode, V}, title = {Predictors of invasion and axillary lymph node metastasis in patients with a core biopsy diagnosis of ductal carcinoma in situ: an analysis of 255 cases.}, journal = {The breast journal}, volume = {17}, number = {3}, pages = {223-229}, doi = {10.1111/j.1524-4741.2011.01069.x}, pmid = {21545433}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; }, abstract = {The diagnosis of ductal carcinoma in situ (DCIS) using core biopsy does not ensure the absence of invasion on final excision. We performed a retrospective analysis of 255 patients with DCIS who had subsequent excision. Clinical, radiologic, and pathologic findings were correlated with risk of invasion and sentinel lymph node (SLN) metastasis. Of 255 patients with DCIS, 199 had definitive surgery and 52 (26%) had invasive ductal carcinoma (IDC) on final excision. Extent of abnormal microcalcification on mammography, and presence of a radiologic/palpable mass and solid type of DCIS were significantly associated with invasion on final excision. Sentinel lymph node biopsy was performed in 131 (65.8%) patients of whom 18 (13.4%) had metastasis. Size of IDC and extent of DCIS on final pathology were significantly associated with positive SLN. Micrometastasis and isolated tumor cells comprised majority (71.4%) of the metastases in DCIS. SLN biopsy should be considered in those with high risk DCIS.}, } @article {pmid21541727, year = {2011}, author = {de Sonneville, LM and Huijbregts, SC and Licht, R and Sergeant, JA and van Spronsen, FJ}, title = {Pre-attentive processing in children with early and continuously-treated PKU. Effects of concurrent Phe level and lifetime dietary control.}, journal = {Journal of inherited metabolic disease}, volume = {34}, number = {4}, pages = {953-962}, pmid = {21541727}, issn = {1573-2665}, mesh = {Adolescent ; Attention/*physiology ; Case-Control Studies ; Child ; Diet ; *Diet Therapy/methods ; Evoked Potentials, Visual ; Female ; Humans ; Male ; Mental Processes/*physiology ; Neuropsychological Tests ; Phenylalanine/analysis/*blood ; Phenylketonurias/blood/*psychology/*therapy ; Time Factors ; }, abstract = {Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain and retina. Similarly, higher lifetime Phe levels and Index of Dietary Control (IDC) were associated with decreased MMN amplitudes, suggesting a reduced ability to respond to stimulus change and poorer triggering of the frontally mediated attention switch. In summary, the present study in children with PKU investigated bottom-up information processing, i.e., triggered by external events, a fundamental prerequisite for the individual's responsiveness to the outside world. Results provide evidence that quality of dietary control may affect the optimal development of these pre-attentive processes, and suggest the existence of windows of vulnerability to Phe exposure.}, } @article {pmid21532879, year = {2011}, author = {Losch, A and Chilek, KD and Zirwas, MJ}, title = {Post-radiation Atypical Vascular Proliferation Mimicking Angiosarcoma Eight Months Following Breast-conserving Therapy for Breast Carcinoma.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {4}, number = {4}, pages = {47-48}, pmid = {21532879}, issn = {2689-9175}, abstract = {Angiosarcoma is an aggressive tumor that most commonly presents on the scalp or face of elderly patients; however, it can develop in pateints with breast cancer following radiation and breast-conserving therapy, complicating 0.1 to 0.2 percent of such cases. Mammography and fine-needle aspiration, though often very useful in evaluating for breast carcinomas and cytological features, are often negative in early stages of angiosarcoma and difficult to interpret. We present the case of a 49-year-old Caucasian woman with a history of stage II invasive ductal carcinoma of the left breast who presented with a two-month history of increased firmness and tenderness in her left breast. On exam, her left breast had significant firmness and hardening of breast tissue with slight erythema of skin. Punch biopsy initially suggested angiosarcoma, but subsequent biopsies instead diagnosed an atypical vascular proliferation. This case represents a patient who presented with an atypical lesion concerning for angiosarcoma. Repeated biopsies were necessary to obtain the correct diagnosis. One biopsy may not be sufficient for distinguishing atypical vascular proliferation from angiosarcoma. We present this case to increase awareness of the difficulty in making this distinction.}, } @article {pmid21527182, year = {2011}, author = {Tsai, SM and Hou, MF and Wu, SH and Hu, BW and Yang, SF and Chen, WT and Chai, CY and Ma, H and Tsai, LY}, title = {Expression of manganese superoxide dismutase in patients with breast cancer.}, journal = {The Kaohsiung journal of medical sciences}, volume = {27}, number = {5}, pages = {167-172}, doi = {10.1016/j.kjms.2010.11.003}, pmid = {21527182}, issn = {2410-8650}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Superoxide Dismutase/*metabolism ; Tumor Burden ; }, abstract = {Breast cancer has become the second leading cancer among females in Taiwan. Even though the etiology of breast cancer is multifactorial, oxidative stress plays an important role in the carcinogenesis. The purpose of this study was to investigate the expression of manganese superoxide dismutase (MnSOD), one of the major antioxidant enzymes that is involved against oxidative stress, in adjacent cancer-free breast tissues and neoplasm tissues within the same patient. Sixty-five breast cancer patients' formalin-fixed tissue blocks, including ductal carcinoma in situ (DCIS) tissues, invasive ductal carcinoma (IDC) tissues, and adjacent cancer-free tissues, were evaluated by immunohistochemical stain. Meanwhile, their demographic and clinical information was also collected. The combined scores of MnSOD-positive cell proportion and MnSOD staining intensity were compared for different tissues within the same patient. The results showed that the mean combined scores of MnSOD expression in adjacent cancer-free tissues (6.33), IDC (5.30), and DCIS (3.78) were significantly different when assessed by repeated-measurement analysis of variance (F=14.17, p<0.001). Additionally, the results revealed that the distribution of strong MnSOD protein expression was 80.0%, 72.3%, and 52.3% in adjacent cancer-free tissues, IDC, and DCIS, respectively. However, there was no statistically significant relationship between the expression of MnSOD and grades of breast cancer or other clinicopathologic variables. We suggest that the expression of MnSOD in neoplasm tissues, independent of the clinicopathologic characters, plays a critical role in breast cancer biology.}, } @article {pmid21521552, year = {2011}, author = {Papantoniou, V and Valsamaki, P and Sotiropoulou, E and Tsaroucha, A and Tsiouris, S and Sotiropoulou, M and Marinopoulos, S and Kounadi, E and Karianos, T and Fothiadaki, A and Archontaki, A and Syrgiannis, K and Ptohis, N and Makris, N and Limouris, G and Antsaklis, A}, title = {Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.}, journal = {Molecular imaging}, volume = {10}, number = {5}, pages = {370-376}, doi = {10.2310/7290.2010.00056}, pmid = {21521552}, issn = {1536-0121}, mesh = {Adult ; Aged ; Breast/*diagnostic imaging/metabolism/pathology ; Breast Neoplasms/*diagnostic imaging/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/pathology ; Cohort Studies ; Female ; Humans ; Hyperplasia ; Linear Models ; Mammography/*methods ; Middle Aged ; Radionuclide Imaging ; Technetium Tc 99m Dimercaptosuccinic Acid/pharmacokinetics ; }, abstract = {The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r = .689, p < .001 and r = .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.}, } @article {pmid21518130, year = {2011}, author = {Yeh, CC and Wang, PH and Lai, CR and Yen, MS and Chao, KC}, title = {Synchronous breast invasive ductal carcinoma and endometrial endometrioid adenocarcinoma: case report.}, journal = {The journal of obstetrics and gynaecology research}, volume = {37}, number = {9}, pages = {1246-1249}, doi = {10.1111/j.1447-0756.2010.01502.x}, pmid = {21518130}, issn = {1447-0756}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Endometrioid/*pathology ; Endometrial Neoplasms/*pathology ; Female ; Humans ; Neoplasms, Multiple Primary/*pathology ; Premenopause ; }, abstract = {Diagnosis of synchronous primary cancers in one patient is a relatively rare event. The well-known synchronous primary cancers of women are combined ovarian and endometrial cancers, especially when both are the endometrioid cell type. Although breast cancer and endometrial cancer are two common female malignancies, they often occur during the postmenopausal period. Therefore, the possibility of concomitant breast cancer and endometrial cancer in a younger woman (premenopausal) is often neglected. The reported case is an example of this situation. A 37-year-old woman was diagnosed with synchronous breast invasive ductal carcinoma and endometrial endometrioid adenocarcinoma. Since this condition is rarely reported, the correlated risk factors are worthy of our attention and the strategy for prevention is highlighted.}, } @article {pmid21517259, year = {2011}, author = {Asif, M and Khadim, MT and Mushtaq, S and Mamoon, N and Akhtar, F and Ali, Z}, title = {Determination of her-2/neu by chromogenic in situ hybridization on borderline (2+) immunohistochemistry cases in carcinoma breast.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {1}, pages = {211-214}, pmid = {21517259}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/therapeutic use ; Breast Neoplasms/*enzymology/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Chromogenic Compounds/chemistry ; Cross-Sectional Studies ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Middle Aged ; Receptor, ErbB-2/genetics/*metabolism ; Trastuzumab ; Young Adult ; }, abstract = {OBJECTIVE: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009.

METHODS: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified).

RESULTS: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification.

CONCLUSION: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.}, } @article {pmid21517252, year = {2011}, author = {Missaoui, N and Jaidene, L and Abdelkrim, SB and Abdelkader, AB and Beizig, N and Yaacoub, LB and Yaacoubi, MT and Hmissa, S}, title = {Breast cancer in Tunisia: clinical and pathological findings.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {1}, pages = {169-172}, pmid = {21517252}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/*pathology/therapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: The aim of this study was to survey the clinical and pathological features of breast cancer in the Center of Tunisia.

DESIGN: Characteristics of all breast cancer cases diagnosed in the Pathology Department, Farhet Hached Hospital, Sousse, Tunisia during a 15-year period (1993-2007) were analyzed.

RESULTS: A total of 2,404 new cases of breast cancer were recorded, only 48 being diagnosed in men. The age-standardized incidence rate was 0.7 and 29.2 per 100,000 in men and women, respectively, with median ages of 48.0 and 64.5 years. Invasive ductal carcinoma was the most common (2,012 cases). Stage II was the most frequent (47.7%) followed by advanced stages (Stage III and IV, 41%).

CONCLUSION: Cancer of the breast remains the most common cancer in the absence of specific screening measures among Tunisian women. Our study justifies the need to plan and develop effective programs aiming at the control and prevention of the spread of breast cancer in Tunisia.}, } @article {pmid21515791, year = {2011}, author = {Hawkins, O and Verma, B and Lightfoot, S and Jain, R and Rawat, A and McNair, S and Caseltine, S and Mojsilovic, A and Gupta, P and Neethling, F and Almanza, O and Dooley, W and Hildebrand, W and Weidanz, J}, title = {An HLA-presented fragment of macrophage migration inhibitory factor is a therapeutic target for invasive breast cancer.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {186}, number = {11}, pages = {6607-6616}, doi = {10.4049/jimmunol.1003995}, pmid = {21515791}, issn = {1550-6606}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/*immunology/therapeutic use ; Antibody Affinity/immunology ; Antibody Specificity/immunology ; Apoptosis/drug effects/immunology ; Breast Neoplasms/drug therapy/*immunology/pathology ; Carcinoma, Ductal, Breast/drug therapy/immunology/pathology ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects/immunology ; Dose-Response Relationship, Drug ; Female ; HLA-A Antigens/*immunology/metabolism ; HLA-A2 Antigen ; Humans ; Kinetics ; Macrophage Migration-Inhibitory Factors/chemistry/*immunology/metabolism ; Mice ; Mice, Nude ; Peptides/immunology/metabolism ; Prognosis ; Protein Binding/immunology ; Xenograft Model Antitumor Assays ; }, abstract = {This report describes a novel HLA/peptide complex with potential prognostic and therapeutic roles for invasive breast cancer. Macrophage migration inhibitory factor (MIF) mediates inflammation and immunity, and MIF overexpression is observed in breast cancer. We hypothesized that the HLA class I of cancerous breast epithelial cells would present MIF-derived peptides. Consistent with this hypothesis, the peptide FLSELTQQL (MIF(19-27)) was eluted from the HLA-A*0201 (HLA-A2) of breast cancer cell lines. We posited that if this MIF(19-27)/HLA-A2 complex was exclusively found in invasive breast cancer, it could be a useful prognostic indicator. To assess the presentation of MIF peptides by the HLA of various cells and tissues, mice were immunized with the MIF(19-27)/HLA-A2 complex. The resulting mAb (RL21A) stained invasive ductal carcinoma (IDC) but not ductal carcinoma in situ, fibroadenoma, or normal breast tissues. RL21A did not stain WBCs (total WBCs) or normal tissues from deceased HLA-A2 donors, substantiating the tumor-specific nature of this MIF/HLA complex. As this MIF/HLA complex appeared specific to the surface of IDC, RL21A was tested as an immunotherapeutic for breast cancer in vitro and in vivo. In vitro, RL21A killed the MDA-MB-231 cell line via complement and induction of apoptosis. In an in vivo orthotopic mouse model, administration of RL21A reduced MDA-MB-231 and BT-20 tumor burden by 5-fold and by >2-fold, respectively. In summary, HLA-presented MIF peptides show promise as prognostic cell surface indicators for IDC and as targets for immunotherapeutic intervention.}, } @article {pmid21492377, year = {2011}, author = {Boccola, MA and Sharma, A and Taylor, C and Wong, LM and Travis, D and Chan, S}, title = {The infusion method trial of void vs standard catheter removal in the outpatient setting: a prospective randomized trial.}, journal = {BJU international}, volume = {107 Suppl 3}, number = {}, pages = {43-46}, doi = {10.1111/j.1464-410X.2011.10044.x}, pmid = {21492377}, issn = {1464-410X}, mesh = {Acute Disease ; Age Factors ; Aged ; Ambulatory Care/methods ; Confidence Intervals ; Device Removal/*methods ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Reference Values ; Risk Assessment ; Statistics, Nonparametric ; Therapeutic Irrigation/methods ; Time Factors ; Treatment Outcome ; Urinary Catheterization/instrumentation/*methods ; Urinary Retention/etiology/physiopathology/*therapy ; Urination/physiology ; }, abstract = {OBJECTIVE: • To ascertain if filling the bladder with warm normal saline before trial of void (TOV) reduces time to decision of outcome of TOV and time to discharge compared with standard in-dwelling catheter (IDC) removal in the outpatient setting.

PATIENTS AND METHODS: • A prospective randomized controlled trial (not blinded) was carried out in the day procedure unit. Randomization was done using computer-generated random numbers. The sample size was calculated based on initial pilot data using α= 0.05 and β= 0.2 and a clinically important reduction of ≥60 min for time to decision of outcome of TOV (primary outcome measure). • In all, 60 consecutive patients were recruited from two referral sources: presentations of acute urinary retention to the emergency department and patients discharged home after failing TOV postoperatively. • The infusion method group (32 patients) had 300-500 mL warm normal saline infused into the bladder before removing their IDC and the control group (28) had standard IDC removal. • Data were collected and analysed using the two-tailed Mann-Whitney U-test. Statistical significance was set at P < 0.05.

RESULTS: • The median time to decision was 135.0 (95% confidence interval CI 95.0-190.0) min in the infusion group and 247.5 (95% CI 189.6-294.1) min in the control group. • Patients undergoing a bladder infusion had a shorter discharge time [180.0 (95% CI 126.0-226.9) min] than patients in the standard-IDC-removal group [262.5 (95% CI 233.8-315.0) min]. • The infusion arm shortened time to decision by 112.5 min (P < 0.001) and time to discharge by 82.5 min (P < 0.001). • Furthermore, patients in the infusion group were 1.56 times more likely to achieve catheter-free state after TOV (risk ratio 1.56, 95% CI 1.03-2.36; P= 0.03).

CONCLUSION: • The infusion method for TOV is safe and expeditious, making it ideal for the outpatient setting. This randomized study shows that the infusion method enables a rapid determination of outcome of TOV with a greater chance of success and shortened discharge times.}, } @article {pmid21503129, year = {2011}, author = {Du, J and Liu, JY and Su, J}, title = {[Comparison of two different tissue decalcification methods for immunohistochemistry].}, journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences}, volume = {43}, number = {2}, pages = {290-294}, pmid = {21503129}, issn = {1671-167X}, mesh = {Bone and Bones/pathology ; Breast Neoplasms/pathology ; Decalcification Technique/*methods ; Female ; Humans ; Immunohistochemistry/*methods ; Male ; Neoplasms/*pathology ; Prostatic Neoplasms/pathology ; Staining and Labeling/*methods ; Thyroid Neoplasms/pathology ; }, abstract = {OBJECTIVE: To investigate the effects of 1% hydrochloric acid and 10% nitric acid on immunohistochemical staining for several antigens.

METHODS: Fifteen cases of focally calcified soft tumors including three cases of thyroid papillary carcinoma, three of breast invasive ductal carcinoma, three of prostate cancer, three of colon adenocarcincoma and three of normal lymph nodes, were selected in this study, and so were nine cases of bone and bone marrow tissue from biopsy and autopsy. Tissue samples were divided into three groups. One group was each soaked into 10% nitric acid for 24, 42 and 48 h, another group was each incubated in 1% hydrochloric acid for 1, 2 and 3 h. The other group which was not treated with acid was regarded as control. Then immunohistochemical staining was conducted in these samples for antigens as follows: ER, PR and Ki-67 in breast invasive ductal carcinoma; TTF-1 in thyroid papillary carcinoma; 34βE12 and P504s in prostate cancer; AE1/AE3, P504s and Ki-67 in colon adenocarcincoma; CD3, CD20 and Ki-67 in lymph nodes; CD3,CD20,CD68,CD235a,MPO,Ki-67,AE1/AE3 and TTF-1 in bone tissue.

RESULTS: After the tissues decalcificated in both acid solutions for some time, the numbers of positive cells decreased and the intensity of immunostaining became weaker, which was proportionate to time. Bone tissue was less influenced than calcified soft tissue. Different antigens showed different sensitivity to the same acid treatment. TTF-1 and Ki-67 were the two most vulnerable antigens among them; while ER, CD3 and CD20 were the least influenced. The effects of decalcification on immunostaining of one antigen were the same in different tissues.

CONCLUSION: In most cases, both hydrochloric acid and nitric acid decalcification can lower the sensitivity of immunohistochemical staining, but have different effects on different antigens. It is better to use 10% nitric acid for decalcification of relatively large bone tissue and to use 1% hydrochloric acid for bone marrow tissues and bone tissues containing much more soft tissue.}, } @article {pmid21502022, year = {2010}, author = {Kulkarni, AS and Gaja, JB}, title = {Formulation and evaluation of liquisolid compacts of diclofenac sodium.}, journal = {PDA journal of pharmaceutical science and technology}, volume = {64}, number = {3}, pages = {222-232}, pmid = {21502022}, issn = {1948-2124}, mesh = {Cellulose ; Chemistry, Pharmaceutical ; *Diclofenac ; Excipients ; Solubility ; *Tablets ; }, abstract = {The technique of liquisolid compacts is a promising method towards enhancing the dissolution of poorly soluble drugs. In the present study, the potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using diclofenac sodium as the model drug. Several formulations of liquisolid compacts having different drug concentration (30% to 50% w/w) and with varying ratios of carrier to coat (i.e., different R values, ranging from 5 to 50) were prepared. Avicel and Aerosil were used as carrier and coat material, respectively, and propylene glycol was used as a nonvolatile liquid to prepare liquid medication. The effect of added liquid on the flowability and compressibility of the final admixture was studied and the effect of drug concentration on the dissolution pattern of diclofenac sodium was investigated. Liquisolid compacts demonstrated significantly higher drug release rates than the pure drug.}, } @article {pmid21501039, year = {2011}, author = {Carvalho, R and Macias, V and Marques-Pinto, G and Afonso, A and Cardoso, J}, title = {Intertriginous pattern of toxic erythema of chemotherapy.}, journal = {Cutaneous and ocular toxicology}, volume = {30}, number = {4}, pages = {309-311}, doi = {10.3109/15569527.2011.572572}, pmid = {21501039}, issn = {1556-9535}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects/therapeutic use ; Erythema/*chemically induced/diagnosis/drug therapy ; Female ; Glucocorticoids/administration & dosage/therapeutic use ; Humans ; Intertrigo/*chemically induced/diagnosis/drug therapy ; Prednisolone/administration & dosage/therapeutic use ; Treatment Outcome ; }, abstract = {Chemotherapeutic agents may induce both local and systemic cutaneous toxicity, and evaluation of these reactions in oncologic patients constitutes a real challenge. The authors describe a 78-year-old Caucasian woman, with a past medical history relevant for right radical mastectomy with axillary dissection because of stage 2 breast invasive ductal carcinoma (T2N3M0), referred to our department because of an intertriginous eruption in her groin. Two weeks before the eruption, a chemotherapy regime with cyclophosphamide, methotrexate, and 5-fluorouracil was performed. Examination revealed erythematous and dusky violaceous papules coalescing into edematous patches in the inguinal intertriginous area, including the internal surface of her thighs, groin, genital area, and intergluteal cleft. Skin cultures for bacteria and fungus were negative. Clinical and histological data were consistent with an intertriginous pattern of toxic erythema of chemotherapy (TEC). Oral prednisolone therapy (0.5 mg/kg) was started, tapered over a 1-week period, and along with general measures that included topical zinc oxide suspension, cutaneous lesions cleared completely within the first days. Although patient reassurance, she refused any kind of new chemotherapy infusions. Due to their high metabolic rate, the skin, mucous membranes, and annexes are one of the most important target organs of the toxicity associated with systemic chemotherapy. Several patterns of cutaneous eruptions to chemotherapy have been reported in the literature. Trying to resolve this issue, recently recommended was a new clinically descriptive term, TEC, in order to emphasize the overlapping features of these entities. Early recognition of this entity is critical, not just from a prognostic standpoint, but also to avoid unnecessary, potentially harmful therapeutic interventions.}, } @article {pmid21498851, year = {2011}, author = {Isohashi, F and Konishi, K and Umegaki, N and Tanei, T and Koizumi, M and Yoshioka, Y}, title = {A case of bullous pemphigoid exacerbated by irradiation after breast conservative radiotherapy.}, journal = {Japanese journal of clinical oncology}, volume = {41}, number = {6}, pages = {811-813}, doi = {10.1093/jjco/hyr049}, pmid = {21498851}, issn = {1465-3621}, mesh = {Acute Disease ; Breast Neoplasms/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/radiotherapy/surgery ; Dose Fractionation, Radiation ; Drug Administration Schedule ; Female ; Glucocorticoids/administration & dosage ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Pemphigoid, Bullous/diagnosis/*drug therapy/etiology/*prevention & control ; Postmenopause ; Prednisone/*administration & dosage ; Radiotherapy, Adjuvant/adverse effects ; }, abstract = {We present a case, considered to be a form of the Koebner phenomenon, of bullous pemphigoid that was exacerbated mainly within the irradiated field after breast conservative radiotherapy. In May 2009, a 60-year-old woman was diagnosed with bullous pemphigoid, which was treated with steroid therapy. The following month, she was diagnosed with breast cancer (invasive ductal carcinoma, pT1cN0M0). After breast conservative surgery in December 2009, conservative radiotherapy to the right breast was performed (50 Gy in 25 fractions). Portal skin showed no serious change (up to grade 1 skin erythema) and no bullous neogenesis during conservative radiotherapy. However, 2 months after conservative radiotherapy, new blisters became exacerbated mainly within the irradiated field but also in the area outside the irradiated field. Increasing the dosage of oral steroid and minocycline resulted in relief of bullous pemphigoid, although patchy skin pigmentation remained especially in the irradiated skin.}, } @article {pmid21498359, year = {2011}, author = {Wang, X and Xu, P and Wang, Y and Grant, EG}, title = {Contrast-enhanced ultrasonographic findings of different histopathologic types of breast cancer.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {52}, number = {3}, pages = {248-255}, doi = {10.1258/ar.2010.100279}, pmid = {21498359}, issn = {1600-0455}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma in Situ/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Medullary/*diagnostic imaging/pathology ; Carcinoma, Papillary/*diagnostic imaging/pathology ; *Contrast Media ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; *Phospholipids ; Retrospective Studies ; Sensitivity and Specificity ; *Sulfur Hexafluoride ; Ultrasonography, Mammary/*methods ; }, abstract = {BACKGROUND: The new application of contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast masses has evolved quickly only in recent years. Nevertheless, mixed results owing to the overlap in characteristics of benign and malignant lesions are simultaneously discovered by most studies, partially attributed to different histopathologic characteristics of breast cancer.

PURPOSE: To explore the characteristics of different histopathologic types of breast cancer at real-time gray-scale CEUS and evaluate its diagnostic value.

MATERIAL AND METHODS: One hundred and one histopathologically confirmed malignant lesions were included. We retrospectively reviewed the contrast-enhanced ultrasonographic findings including morphologic features, quantitative parameters, and correlated them with histopathology. True-positive rate was calculated to assess the diagnostic performance of CEUS.

RESULTS: The 101 malignancies displayed irregular shape (72 [71%]), poorly-defined margin (73 [72%]), penetrating or tortuous surrounding vessels (79 [78%]), heterogeneous enhancement (84 [83%]), including focal perfusion defects (24 [24%]). For each histopathologic type, 87% (58/67) of invasive ductal carcinoma (IDC) showed heterogeneous enhancement. Of all the 24 perfusion defects, IDC account for 88% (21/24). Low average peak intensity (PI) of 4.9 was detected in this type. Ductal carcinoma in situ (DCIS) excellently showed the features of irregular shape (82% [14/17]), poorly-defined margin (82% [14/17]), heterogeneous enhancement (94% [16/17]). While 83% (5/6) of medullary carcinoma exhibited regular shape, well-defined margin, homogenous enhancement, and high average PI value of 9.6. Invasive lobular carcinoma showed similar enhancement pattern to that of IDC. Intraductal papillary carcinoma displayed high average PI value of 8.1. The overall true-positive rate for conventional US and CEUS was 88%, 86%, respectively. DCIS, medullary carcinoma, and intraductal papillary carcinoma achieved an improved true-positive rate (94%, 100% and 100%, respectively).

CONCLUSION: The imaging characteristics of CEUS are variable in different histopathologic types of breast cancer. CEUS does not appear to be superior to conventional ultrasound as a diagnostic tool overall, however, it is a useful adjunct to conventional ultrasound in diagnosing some special types of breast cancer.}, } @article {pmid21496280, year = {2011}, author = {Umekita, Y and Ohi, Y and Souda, M and Rai, Y and Sagara, Y and Sagara, Y and Tamada, S and Tanimoto, A}, title = {Maspin expression is frequent and correlates with basal markers in triple-negative breast cancer.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {36}, pmid = {21496280}, issn = {1746-1596}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*metabolism/pathology ; ErbB Receptors/metabolism ; Female ; Humans ; Keratin-14/metabolism ; Keratin-5/metabolism ; Keratin-6/metabolism ; Middle Aged ; Retrospective Studies ; Serpins/*metabolism ; }, abstract = {BACKGROUND: Maspin is a unique member of the serine protease inhibitor superfamily and its expression is found in myoepithelial cells of normal mammary glands; therefore, it has been considered to be a myoepithelial marker. We previously reported that maspin was frequently expressed in biologically aggressive breast cancers. In turn, triple-negative (TN) breast cancer is a subtype of tumor with aggressive clinical behavior and shows frequent expression of basal markers. We hypothesized that maspin expression may be frequent and correlate with basal rather than myoepithelial markers in TN breast cancer.

METHODS: Paraffin-embedded 135 TN invasive ductal carcinoma tissue samples were immunohistochemically investigated using the Dako Envision+ kit and primary antibodies for maspin, basal (CK5/6, EGFR, CK14) and myoepithelial markers (p63, CD10). The correlation between maspin expression and relapse-free survival (RFS) was investigated by the log-rank test.

RESULTS: The positive rate for maspin was 85.9% and significantly correlated with younger age (P=0.0015), higher histological grade (P=0.0013), CK5/6 positivity (P<0.0001), CK14 positivity (P=0.0034) and the basal-like subtype defined by CK5/6, EGFR and CK14 positivity (P=0.013). The positive rates for CK5/6, EGFR, CK14, CD10 and p63 were 59.2%, 48.9%, 34.1%, 17.8% and 12.6%, respectively. There was no significant correlation between maspin expression and RFS.

CONCLUSIONS: The positive rate for maspin is the highest among known basal and myoepithelial markers, and strongly correlates with basal markers in TN breast cancer. These results suggested that maspin could be a candidate for a therapeutic target for TN breast cancer.}, } @article {pmid21492761, year = {2011}, author = {Hershberger, RE and Siegfried, JD}, title = {Update 2011: clinical and genetic issues in familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {57}, number = {16}, pages = {1641-1649}, pmid = {21492761}, issn = {1558-3597}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01 HL058626-11/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Cardiomyopathy, Dilated/diagnosis/genetics ; Genetic Testing/methods/trends ; Genotype ; High-Throughput Nucleotide Sequencing/methods/trends ; Humans ; Mutation/genetics ; Phenotype ; }, abstract = {A great deal of progress has recently been made in the discovery and understanding of the genetics of familial dilated cardiomyopathy (FDC). A consensus has emerged that with a new diagnosis of idiopathic dilated cardiomyopathy (IDC), the clinical screening of first-degree family members will reveal FDC in at least 20% to 35% of those family members. Point mutations in 31 autosomal and 2 X-linked genes representing diverse gene ontogeny have been implicated in causing FDC but account for only 30% to 35% of genetic causes. Next-generation sequencing methods have dramatically decreased sequencing costs, making clinical genetic testing feasible for extensive panels of dilated cardiomyopathy genes. Next-generation sequencing also provides opportunities to discover additional genetic causes of FDC and IDC. Guidelines for evaluation and testing of FDC and IDC are now available, and when combined with FDC genetic testing and counseling, will bring FDC/IDC genetics to the forefront of cardiovascular genetic medicine.}, } @article {pmid21486440, year = {2011}, author = {Soria, G and Ofri-Shahak, M and Haas, I and Yaal-Hahoshen, N and Leider-Trejo, L and Leibovich-Rivkin, T and Weitzenfeld, P and Meshel, T and Shabtai, E and Gutman, M and Ben-Baruch, A}, title = {Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition.}, journal = {BMC cancer}, volume = {11}, number = {}, pages = {130}, pmid = {21486440}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Chemokine CCL2/metabolism ; Chemokine CCL5/metabolism ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Inflammation Mediators/*metabolism/pharmacology ; Interleukin-1beta/pharmacology ; Microscopy, Confocal ; Middle Aged ; Neoplasm Recurrence, Local ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {BACKGROUND: The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1β were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course.

METHODS: The expression of CCL2, CCL5, TNFα and IL-1β was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments.

RESULTS: CCL2, CCL5, TNFα and IL-1β were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1β in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1β expression. These results suggest progression-related roles for TNFα and IL-1β in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1β compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1β) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1β acts jointly with other pro-malignancy factors to promote disease relapse.

CONCLUSIONS: Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1β may be important for disease course, and that TNFα & IL-1β may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.}, } @article {pmid21483103, year = {2011}, author = {Ammar, A and Mohammed, RA and Salmi, M and Pepper, M and Paish, EC and Ellis, IO and Martin, SG}, title = {Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {34}, number = {1-2}, pages = {67-78}, doi = {10.3233/ACP-2011-0002}, pmid = {21483103}, issn = {2210-7185}, mesh = {Adult ; Aged ; Blood Vessels/metabolism ; Breast Neoplasms/*metabolism/*pathology ; Cell Adhesion Molecules, Neuronal/*metabolism ; Dendritic Cells/metabolism ; Endothelium, Lymphatic/metabolism ; Female ; Flow Cytometry ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*metabolism/*pathology ; Lymphatic Metastasis/*pathology ; Macrophages/metabolism ; Middle Aged ; Palatine Tonsil/metabolism ; Paraffin Embedding ; Receptors, Lymphocyte Homing/*metabolism ; Tissue Fixation ; }, abstract = {BACKGROUND: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process.

METHODS: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, Mϕ). In vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry.

RESULTS: In vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in Mϕ/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with Mϕ indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004).

CONCLUSIONS: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.}, } @article {pmid21479713, year = {2011}, author = {Vaiyapuri, GR and Han, HC and Lee, LC and Tseng, LA and Wong, HF}, title = {Use of the Gynecare Prolift system in surgery for pelvic organ prolapse: 1-year outcome.}, journal = {International urogynecology journal}, volume = {22}, number = {7}, pages = {869-877}, pmid = {21479713}, issn = {1433-3023}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Buttocks ; Clinical Competence ; Female ; Gynecologic Surgical Procedures/adverse effects/instrumentation/*methods ; Hematoma/etiology ; Humans ; Learning Curve ; Length of Stay ; Middle Aged ; Pain, Postoperative/etiology ; Pelvic Organ Prolapse/complications/*surgery ; Recurrence ; Reoperation ; Retrospective Studies ; Suburethral Slings ; *Surgical Mesh ; Surgical Wound Dehiscence/etiology ; Thigh ; Treatment Outcome ; Urinary Incontinence, Stress/etiology/surgery ; Vagina/*surgery ; }, abstract = {INTRODUCTION AND HYPOTHESIS: This retrospective study reports the 1-year outcome in women who underwent mesh-augmented Prolift surgery performed from 2006 to 2008. There were a total of 254 patients, with 128, 106 and 20 patients receiving total, anterior and posterior Prolift, respectively.

METHODS: Incidence of thigh pain was lower in 2008 compared to 2006 and 2007 (p < 0.0001). The percentage of patients requiring blood transfusions (p = 0.09), duration of IDC ≥ 7 days (p = 0.27), wound dehiscence and re-operation rate were lower in 2008 in contrast to 2006 and 2007 (p = 0.43). Only 209 patients (82.3%) were available for review at 1 year. There were two (1.0%) cases of recurrent vault prolapse.

RESULTS: The subjective and objective cure rates at 1 year after this mesh implant surgery in 2006, 2007 and 2008 were 92.1% and 92.1%; 97.0% and 92.4% and 100% and 97%, respectively. The mesh erosion rate was remarkably lower in 2008 as compared to 2007 and 2006 (p < 0.001).

CONCLUSIONS: This synthetic mesh-augmented implant surgery is effective and safe, and surgical outcome appears related to the learning curve of the surgeon.}, } @article {pmid21477174, year = {2011}, author = {Stolnicu, S and Preda, O and Kinga, S and Marian, C and Nicolau, R and Andrei, S and Nicolae, A and Nogales, FF}, title = {Florid, papillary endosalpingiosis of the axillary lymph nodes.}, journal = {The breast journal}, volume = {17}, number = {3}, pages = {268-272}, doi = {10.1111/j.1524-4741.2011.01081.x}, pmid = {21477174}, issn = {1524-4741}, mesh = {Axilla ; Breast Neoplasms/complications/metabolism/*pathology ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Diseases/complications/metabolism/*pathology ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {A 55-year-old woman underwent radical mastectomy and axillary node dissection because of an invasive ductal carcinoma with neuroendocrine features. Histologically, all 22 sampled lymph nodes had widespread cystic inclusions lined by a regular, serous-type epithelium positive for cytokeratin-7, WT-1, CA125, and estrogen receptors. Papillary projections were found in the lumen of some cysts. The lesions were consistent with florid, papillary endosalpingiosis (FPE), a hitherto unreported condition in a supradiaphragmatic location. Metastases from papillary carcinomas of ovary, breast, or thyroid were excluded considering the lesion's immunophenotype (negative for mammaglobin and TTF-1) and the absence of both atypical features and a concurrent abdominal serous tumor. In only one node, lesions co-existed with a metastasis of breast carcinoma. Supradiaphragmatic FPE represents a pitfall in the differential diagnosis of metastases, especially in sentinel nodes, since it may increase their size and reveal an unusual ultrasonographic image. Clinicopathologic findings and a focused immunohistochemical study led to the correct diagnosis of this benign lesion.}, } @article {pmid21476934, year = {2011}, author = {Singh, AK and Parshad, R and Pasi, S and Madhavan, T and Das, SN and Mishra, B and Gill, K and Dalal, K and Dey, S}, title = {Prognostic significance of cyclooxygenase-2 and response to chemotherapy in invasive ductal breast carcinoma patients by real time surface plasmon resonance analysis.}, journal = {DNA and cell biology}, volume = {30}, number = {10}, pages = {801-807}, doi = {10.1089/dna.2011.1215}, pmid = {21476934}, issn = {1557-7430}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration & dosage/therapeutic use ; *Biomarkers, Tumor/blood/genetics ; Blotting, Western ; Breast Neoplasms/blood/*diagnosis/mortality/pathology/therapy ; Breast Neoplasms, Male/blood/*diagnosis/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/blood/*diagnosis/mortality/pathology/therapy ; Chemotherapy, Adjuvant ; *Cyclooxygenase 2/blood/genetics ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Prognosis ; Surface Plasmon Resonance/instrumentation/*methods ; }, abstract = {Cyclooxygenase-2 (COX-2), an inducible enzyme, has been implicated in the progression and angiogenesis of breast cancer. The aim of the study is to quantify the concentration of COX-2 and its association with clinico-pathological parameters and response to treatment in patients with invasive ductal carcinoma receiving both neo-adjuvant and adjuvant chemotherapy. The level of COX-2 was estimated using a novel biosensor-based surface plasmon resonance technique in serum of 84 patients with breast cancer (48 patients of neo-adjuvant chemotherapy and 36 patients of adjuvant chemotherapy) and 40 age- and gender-matched normal individuals. A significant increase in COX-2 level was observed in patients compared with normal individuals (p>0.0001). The COX-2 level in serum was found to be significantly higher in patients with lymph node involvement (p<0.0061). 68% (33/48) of the patients receiving neo-adjuvant chemotherapy showed significantly (p<0.0025) reduced COX-2 levels. This study shows significant decrease of COX-2 level in patients with breast cancer treated with both neo-adjuvant and adjuvant chemotherapy. Estimation of COX-2 level in serum may serve as a tumor biomarker in patients with breast cancer.}, } @article {pmid21472867, year = {2012}, author = {Sentani, K and Tashiro, T and Uraoka, N and Aosaki, Y and Yano, S and Takaeko, F and Yasui, W}, title = {Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.}, journal = {Diagnostic cytopathology}, volume = {40}, number = {7}, pages = {624-628}, doi = {10.1002/dc.21638}, pmid = {21472867}, issn = {1097-0339}, mesh = {Aged ; Biopsy, Fine-Needle ; Breast/pathology ; Breast Neoplasms/chemistry/diagnosis/*pathology ; Cystadenocarcinoma, Mucinous/chemistry/diagnosis/*pathology ; Cytoplasm/pathology ; Female ; Humans ; Immunohistochemistry/methods ; Mucins/chemistry ; }, abstract = {Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation.}, } @article {pmid21464011, year = {2011}, author = {Sakr, R and Fleury, J and Prengel, C and Roynard, P and Daraï, E and Uzan, S and Rouzier, R and Bernaudin, JF}, title = {[Are centrosomal abnormalities correlated to DNA ploidy in breast cancer?].}, journal = {Annales de biologie clinique}, volume = {69}, number = {2}, pages = {181-189}, doi = {10.1684/abc.2011.0525}, pmid = {21464011}, issn = {0003-3898}, mesh = {Breast Neoplasms/*genetics ; *Centrosome ; DNA, Neoplasm/*genetics ; Humans ; *Ploidies ; Tumor Cells, Cultured ; }, abstract = {ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.}, } @article {pmid21462680, year = {2011}, author = {Schnitzler, C and Seifert, L and Chollet, D}, title = {Arm coordination and performance level in the 400-m front crawl.}, journal = {Research quarterly for exercise and sport}, volume = {82}, number = {1}, pages = {1-8}, doi = {10.1080/02701367.2011.10599716}, pmid = {21462680}, issn = {0270-1367}, mesh = {Adult ; Analysis of Variance ; Athletic Performance/*physiology ; Biomechanical Phenomena ; Humans ; Male ; Swimming/*physiology ; Upper Extremity/*physiology ; Video Recording ; Young Adult ; }, abstract = {The purpose of this study was to determine whether the Index of Coordination (IdC) and the propulsive phase durations can differentiate performance level during a maximal 400-m front crawl swim trial. Sixteen male swimmers constituted two groups based on performance level (G1: experts; G2: recreational). All participants swam the 400-m front crawl at maximal speed. Video analysis determined the stroke (swimming speed, stroke length, stroke rate) and coordination (IdC) parameters for every 50 m. Both stroke and coordination parameters discriminated performance level. The expert group had significantly higher values for speed and stroke length and lower values for the relative propulsive phase duration and IdC (p < .05). However there was no significant change in coordination parameters for either group throughout the trial. This suggests that, when associated with greater stroke length, catch-up coordination can be an efficient coordination mode that reflects optimal drag/propulsion adaptation. This finding provides new insight into swimmers' adaptations in a middle-distance event.}, } @article {pmid21455579, year = {2011}, author = {Matsumoto, K and Yamamoto, N and Hagiwara, S and Saito, M and Furue, H and Shigetomi, T and Narita, Y and Mitsudo, K and Tohnai, I and Kobayashi, T and Ueda, M}, title = {Optimization of hyperthermia and dendritic cell immunotherapy for squamous cell carcinoma.}, journal = {Oncology reports}, volume = {25}, number = {6}, pages = {1525-1532}, doi = {10.3892/or.2011.1232}, pmid = {21455579}, issn = {1791-2431}, mesh = {Animals ; Blotting, Western ; Carcinoma, Squamous Cell/*therapy ; Dendritic Cells/*transplantation ; Female ; Fluorescent Antibody Technique ; HSP70 Heat-Shock Proteins/biosynthesis ; *Hyperthermia, Induced ; Immunotherapy/*methods ; Mice ; Mice, Inbred C3H ; }, abstract = {The aims of this study were to explore the feasibility of a novel combination therapy comprising hyperthermia (HT) and dendritic cell (DC) application for squamous cell carcinoma (SCC), and to optimize the conditions of this therapy. In vitro, the correlation between maturation of DCs by co-culture with SCCVII cells and HT was investigated. DCs did not mature in simple HT (43 °C for 30 min) with SCCVII cells. On the other hand, DC maturation occurred in additional mild HT (mHT: 41 °C for 30 min) with simple HT. To assess whether additional mHT was effective, in vivo combined treatment was performed using tumor-bearing C3H/HeJ mice. A more suppressive effect of tumor growth was observed, and cytotoxic T cell infiltration was significantly increased by adding mHT compared to conventional only simple HT with DCs. These phenomena also occurred in non-treated contralateral tumors as well as treated ones. Our data suggest that the combination of 43 °C preheated simple HT SCCVII tumors and additional 41 °C heat mHT promotes DC maturation, resulting in suppression of tumor growth systemically and lifetime prolongation in mice. A three-step process of additional mHT after local HT and intratumoral immature DC (iDC) injection could be a more effective and novel method for the treatment of SCC.}, } @article {pmid21448950, year = {2011}, author = {Thakur, SB and Brennan, SB and Ishill, NM and Morris, EA and Liberman, L and Dershaw, DD and Bartella, L and Koutcher, JA and Huang, W}, title = {Diagnostic usefulness of water-to-fat ratio and choline concentration in malignant and benign breast lesions and normal breast parenchyma: an in vivo (1) H MRS study.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {33}, number = {4}, pages = {855-863}, doi = {10.1002/jmri.22493}, pmid = {21448950}, issn = {1522-2586}, mesh = {Adipose Tissue/*metabolism ; Adult ; Aged ; Area Under Curve ; Biomarkers/metabolism ; Body Water/*metabolism ; Breast/*physiology ; Breast Diseases/*diagnosis/pathology ; Breast Neoplasms/*diagnosis/pathology ; Choline/*metabolism ; Female ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Male ; Middle Aged ; Models, Statistical ; ROC Curve ; }, abstract = {PURPOSE: To compare total choline concentrations ([Cho]) and water-to-fat (W/F) ratios of subtypes of malignant lesions, benign lesions, and normal breast parenchyma and determine their usefulness in breast cancer diagnosis. Reference standard was histology.

MATERIALS AND METHODS: In this HIPPA compliant study, proton MRS was performed on 93 patients with suspicious lesions (>1 cm) who underwent MRI-guided interventional procedures, and on 27 prospectively accrued women enrolled for screening MRI. (W/F) and [Cho] values were calculated using MRS data.

RESULTS: Among 88 MRS-evaluable histologically-confirmed lesions, 40 invasive ductal carcinoma (IDC); 10 invasive lobular carcinoma (ILC); 4 ductal carcinoma in situ (DCIS); 3 invasive mammary carcinoma (IMC); 31 benign. No significant difference observed in (W/F) between benign lesions and normal breast tissue. The area under curve (AUC) of receiver operating characteristic (ROC) curves for discriminating the malignant group from the benign group were 0.97, 0.72, and 0.99 using [Cho], (W/F) and their combination as biomarkers, respectively. (W/F) performs significantly (P < 0.0001;AUC = 0.96) better than [Cho] (AUC = 0.52) in differentiating IDC and ILC lesions.

CONCLUSION: Although [Cho] and (W/F) are good biomarkers for differentiating malignancy, [Cho] is a better marker. Combining both can further improve diagnostic accuracy. IDC and ILC lesions have similar [Cho] levels but are discriminated using (W/F) values.}, } @article {pmid21445088, year = {2012}, author = {van de Ven, R and Lindenberg, JJ and Reurs, AW and Scheper, RJ and Scheffer, GL and de Gruijl, TD}, title = {Preferential Langerhans cell differentiation from CD34(+) precursors upon introduction of ABCG2 (BCRP).}, journal = {Immunology and cell biology}, volume = {90}, number = {2}, pages = {206-215}, doi = {10.1038/icb.2011.25}, pmid = {21445088}, issn = {1440-1711}, mesh = {ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/*metabolism ; Antigens, CD1/metabolism ; Antigens, CD34/metabolism ; Breast Neoplasms ; Cell Differentiation ; Cell Line, Tumor ; Dendritic Cells/cytology/immunology/*metabolism ; Female ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Langerhans Cells/cytology/immunology/*metabolism ; Lectins, C-Type/immunology/metabolism ; Leukemia, Myeloid, Acute ; Neoplasm Proteins/*metabolism ; Skin/metabolism ; Transcription Factor RelB/metabolism ; Transforming Growth Factor beta/immunology/metabolism ; }, abstract = {Epidermal Langerhans cells (LC) and dermal interstitial dendritic cells (IDC) were found to express the ATP-binding cassette (ABC) transporter breast cancer resistance protein (BCRP; ABCG2). Also, low BCRP expression was present on CD34(+) blood DC precursors and expression was increased upon their differentiation to LC. The CD34(+) acute myeloid leukemia-derived DC cell line MUTZ3 can be cultured into LC or IDC, depending on the cytokine cocktail used. Introduction of functional BCRP in MUTZ3 progenitor cells through retroviral transduction resulted in the emergence of typical LC-characteristics in IDC cultures; the majority of cells remained negative for the IDC-specific C-type lectin DC-SIGN, but rather displayed enhanced expression of the LC-specific C-type lectin Langerin and characteristic high expression levels of CD1a. BCRP-induced skewing toward LC-like differentiation coincided with early RelB expression in 'IDC', derived from MUTZ3-BCRP, and depended on endogenous transforming growth factor beta (TGF-β) production. Intriguingly, cellular BCRP localization differed between skin LC and IDC, and a more cytoplasmic BCRP localization, as observed in primary skin LC, seemed to relate to LC-like differentiation in IDC cultures upon BCRP introduction in MUTZ3 progenitors. Together these data support a role for BCRP in preferential LC differentiation from CD34(+) myeloid DC progenitors.}, } @article {pmid21443541, year = {2011}, author = {Kayashima, T and Nakata, K and Ohuchida, K and Ueda, J and Shirahane, K and Fujita, H and Cui, L and Mizumoto, K and Tanaka, M}, title = {Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia.}, journal = {Cancer science}, volume = {102}, number = {6}, pages = {1137-1143}, doi = {10.1111/j.1349-7006.2011.01936.x}, pmid = {21443541}, issn = {1349-7006}, mesh = {Carcinoma in Situ/genetics/metabolism/pathology ; Carcinoma, Pancreatic Ductal/*genetics/metabolism/pathology/secondary ; *Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; *Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics ; Lymphatic Metastasis ; Membrane Proteins/biosynthesis/*genetics ; Microarray Analysis ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Polymerase Chain Reaction ; RNA, Messenger/biosynthesis/genetics ; RNA, Small Interfering ; *Tumor Microenvironment ; }, abstract = {A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P < 0.001) and pancreatic intraepithelial neoplasia cells (P = 0.082). In analyses of IDC cells, the levels of Insig2 mRNA expression were significantly higher in late-stage patients than in early-stage patients. The present data suggest that Insig2 is associated with the malignant potential of pancreatic cancer under hypoxic conditions.}, } @article {pmid21432691, year = {2011}, author = {Mikulincer, M and Shaver, PR and Rom, E}, title = {The effects of implicit and explicit security priming on creative problem solving.}, journal = {Cognition & emotion}, volume = {25}, number = {3}, pages = {519-531}, doi = {10.1080/02699931.2010.540110}, pmid = {21432691}, issn = {1464-0600}, mesh = {Adult ; Anxiety/psychology ; Avoidance Learning ; *Creativity ; Emotions ; Female ; Humans ; Male ; Mental Recall ; *Object Attachment ; *Problem Solving ; Psychomotor Performance ; Social Control, Informal ; *Unconscious, Psychology ; }, abstract = {Attachment theory is a theory of affect regulation as it occurs in the context of close relationships. Early research focused on regulation of emotions through maintenance of proximity to supportive others (attachment figures) in times of need. Recently, emphasis has shifted to the regulation of emotion, and the benefits of such regulation for exploration and learning, via the activation of mental representations of attachment figures (security priming). We conducted two studies on the effects of implicit and explicit security priming on creative problem solving. In Study 1, implicit security priming (subliminal presentation of attachment figures' names) led to more creative problem solving (compared with control conditions) regardless of dispositional attachment anxiety and avoidance. In Study 2, the effects of explicit security priming (recalling experiences of being well cared for) were moderated by anxiety and avoidance. We discuss the link between attachment and exploration and the different effects of implicit and explicit security priming.}, } @article {pmid21427206, year = {2011}, author = {Goldwich, A and Prechtel, AT and Mühl-Zürbes, P and Pangratz, NM and Stössel, H and Romani, N and Steinkasserer, A and Kummer, M}, title = {Herpes simplex virus type I (HSV-1) replicates in mature dendritic cells but can only be transferred in a cell-cell contact-dependent manner.}, journal = {Journal of leukocyte biology}, volume = {89}, number = {6}, pages = {973-979}, doi = {10.1189/jlb.0310180}, pmid = {21427206}, issn = {1938-3673}, mesh = {Animals ; Blotting, Western ; Cell Adhesion ; Cell Communication ; Cell Movement ; Chlorocebus aethiops ; Dendritic Cells/*immunology/metabolism/*virology ; Herpes Simplex/immunology/metabolism/*transmission ; Herpesvirus 1, Human/*physiology ; RNA, Messenger/genetics ; RNA, Viral/genetics ; Vero Cells ; Viral Proteins/genetics/metabolism ; Virion/*physiology ; *Virus Replication ; }, abstract = {HSV-1 is a very successful representative of the α-herpesvirus family, and ∼ 90% of the population is seropositive for this particular virus. Although the pathogen usually causes the well-known mild lesions on the lips, also, severe infections of the eye or the brain can be observed in rare cases. It is well known, that this virus can efficiently infect the most potent APCs, i.e., the DCs, in their immature and mature state. Although the infection of the iDC has been shown to be productive, infection of mMDDCs is believed to be abortive in the early phase of the viral replication cycle. In line with these findings, no virus particles can be detected in the supernatant of HSV-1-infected mMDDC. In this study, however, we show for the first time that this pathogen completes its replication cycle in mMDDCs. We detected the presence of viral gene transcripts of all three phases of the replication cycle, as well as of late viral proteins, and even the generation of small amounts of progeny virus. Although we could confirm the findings that these particles are not released into the supernatant, surprisingly, the newly generated viral particles can be passed on to Vero cells, as well as to primary keratinocytes in a cell-cell contact-dependent manner. Finally, we provide evidence that the viral gE is involved in the transfer of infectious virus from mMDDCs to other permissive cells.}, } @article {pmid21423094, year = {2011}, author = {Sosonkina, N and Nakashima, M and Ohta, T and Niikawa, N and Starenki, D}, title = {Down-regulation of ABCC11 protein (MRP8) in human breast cancer.}, journal = {Experimental oncology}, volume = {33}, number = {1}, pages = {42-46}, pmid = {21423094}, issn = {2312-8852}, mesh = {ATP-Binding Cassette Transporters/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/pathology ; Down-Regulation/*genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; RNA, Messenger/metabolism ; }, abstract = {AIM: To investigate the expression of ABCC11 (MRP8) protein in normal breast tissue, and examine the difference in ABCC11 mRNA and protein expression between normal breast and breast cancer tissues taking into account ABCC11 genotype (a functional SNP, rs17822931) and estrogen receptor (ER) status.

METHODS: Sections of paraffin-embedded normal and malignant tissues from 10 patients with invasive ductal carcinoma were used for immunohistochemical analysis. DNA and RNA were extracted from the same sections and used for genotyping and ABCC11 transcript expression measurement by quantitative RT-PCR.

RESULTS: A strong expression of ABCC11 was found in epithelial and myoepithelial cells of normal breast lobules and ducts in individuals with different ABCC11 genotypes. A predominant decrease of ABCC11 expression was observed in malignant tissue compared to normal beast specimen (8 of 10 cases), despite four out of ten tumors showed the elevated ABCC11 mRNA level as compared to the normal counterpart. Neither ABCC11 mRNA nor protein expression in normal or cancerous tissue correlated with ER status.

CONCLUSION: The expression of ABCC11 protein appears to be decreased in most BC. The effect of ABCC11 protein on breast cancer chemosensitivity is likely to be more complex than that which can be directly inferred from ABCC11 genotype and mRNA expression level in the tumor.}, } @article {pmid21421525, year = {2011}, author = {Wernicke, AG and Goltser, Y and Trichter, S and Sabbas, A and Gaan, J and Swistel, AJ and Magro, CM}, title = {Morphea as a consequence of accelerated partial breast irradiation.}, journal = {Clinical breast cancer}, volume = {11}, number = {1}, pages = {67-70}, doi = {10.3816/CBC.2011.n.012}, pmid = {21421525}, issn = {1938-0666}, mesh = {Aged ; Brachytherapy/*adverse effects ; Breast Neoplasms/complications/*radiotherapy ; Carcinoma, Ductal, Breast/complications/*radiotherapy ; Female ; Humans ; Radiation Injuries/drug therapy/*etiology ; Scleroderma, Localized/drug therapy/*etiology ; Treatment Outcome ; }, abstract = {Morphea is a localized form of scleroderma usually unaccompanied by the typical systemic stigmata that characterize progressive systemic scleroderma. It rarely manifests at the site of whole breast external-beam radiation therapy. We present an unusual case of radiation-induced morphea (RIM) that occurred after accelerated partial breast irradiation (APBI) using intracavitary Contura brachytherapy. A 65-year-old white woman was treated for stage IIA invasive ductal carcinoma of the left breast with APBI to a dose of 34 Gy in 3.4-Gy fractions twice daily over the course 5 days with intracavitary brachytherapy. At 1.5 years after completion of APBI, the patient developed an area of tenderness, erythema, and induration at the site of irradiation. A skin biopsy was consistent with morphea. To our knowledge, this is the first case of RIM confined to the area of APBI.}, } @article {pmid21415700, year = {2011}, author = {Ross, DS and Hoda, SA}, title = {Microinvasive (T1mic) lobular carcinoma of the breast: clinicopathologic profile of 16 cases.}, journal = {The American journal of surgical pathology}, volume = {35}, number = {5}, pages = {750-756}, doi = {10.1097/PAS.0b013e318212acd3}, pmid = {21415700}, issn = {1532-0979}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Lobular/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary/metabolism/pathology ; }, abstract = {INTRODUCTION: The entity of microinvasive lobular carcinoma (MILC,<0.1 cm) of the breast remains hitherto poorly characterized.

METHODS: Clinical and pathologic material of cases in which MILC was either suspected or diagnosed over an 18-year period (1991 to 2009) was studied. Only cases in which MILC could be indisputably established, by immunohistochemical stains in equivocal cases, were included.

RESULTS: Sixteen (0.02%) cases were confirmed to be MILC among 75,250 breast cases during the study period. Mean age of patients was 52 years (range, 41 to 65 y). Patients presented with either radiographic (13 cases) or palpable (3 cases) abnormality. MILC was unilateral in all cases (right: 8, left: 8). Mean number of microinvasive foci was 1.5 (range, 1 to 5). MILCs were associated with lobular carcinoma in situ (LCIS) predominantly of the classical type in 11 cases, of the florid type in 4 cases, and of the pleomorphic type (with high-grade nuclei) in 1 case. Slight enhancement of stromal cellularity was the only histologic hint of MILC at low-power microscopy. Six MILC cases, in which results could be obtained, were positive for both estrogen receptor and progesterone receptor, and all 6 were negative for HER2/neu. The final surgical procedure was excisional biopsy (8 cases), ipsilateral mastectomy (6 cases), and bilateral mastectomy (2 cases). Synchronous invasive ductal carcinoma (2 cases, 1 of which was contralateral), intraductal carcinoma (2 cases), and LCIS (16 cases) were identified therein. Axillary lymph node biopsies (including 9 sentinel lymph node samplings) were performed in 13 cases, with negative results in each. All patients were alive without evidence of recurrence or of metastases in a mean follow-up of 24 months (range, 1 to 72 mo).

CONCLUSIONS: On the basis of this study, MILC is a rare disease that is typically associated with classical, florid, or pleomorphic forms of LCIS. MILC cases in this series showed low morbidity and no metastatic potential, at least in the short term.}, } @article {pmid21410943, year = {2011}, author = {Pillay, K and McCleod, H and Chetty, R and Hall, P}, title = {A study to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.}, journal = {World journal of surgical oncology}, volume = {9}, number = {}, pages = {31}, pmid = {21410943}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/mortality/pathology ; Cyclin E/*analysis ; Cyclin-Dependent Kinase Inhibitor p27/*analysis ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.

METHODS: Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.

RESULTS: There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup.

CONCLUSION: This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.}, } @article {pmid21410586, year = {2011}, author = {Zhang, F and Qi, X and Xu, Y and Zhou, Y and Zhang, Y and Fan, L and Zhong, L and Yang, X and Jiang, J}, title = {Breast cancer and Poland's syndrome: a case report and literature review.}, journal = {The breast journal}, volume = {17}, number = {2}, pages = {196-200}, doi = {10.1111/j.1524-4741.2010.01042.x}, pmid = {21410586}, issn = {1524-4741}, mesh = {Adult ; Breast Neoplasms/*complications/*diagnosis/surgery ; Carcinoma, Ductal/*complications/*diagnosis/surgery ; Female ; Humans ; Lymphatic Metastasis/diagnosis ; Mammography ; Mastectomy, Modified Radical ; Neoplasm Invasiveness ; Poland Syndrome/*complications/diagnostic imaging/pathology ; Ultrasonography ; }, abstract = {Poland's syndrome is a rare congenital development malformation characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It is also known to be associated with some malignant diseases. We herein report a case of Poland's syndrome associated with invasive ductal carcinoma of breast, and review the literatures to investigate the clinical characteristics of breast cancer with Poland's syndrome.}, } @article {pmid21403445, year = {2011}, author = {Kusama, M}, title = {[A case of secondary inflammatory breast cancer with multiple metastases in which operation was possible through letrozole monotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {3}, pages = {419-422}, pmid = {21403445}, issn = {0385-0684}, mesh = {Antineoplastic Agents/*therapeutic use ; Biopsy, Needle ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/pathology/surgery ; Catheter Ablation ; Combined Modality Therapy ; Female ; Humans ; Inflammatory Breast Neoplasms/diagnostic imaging/*drug therapy/secondary ; Letrozole ; Middle Aged ; Neoplasm Metastasis/drug therapy ; Nitriles/*therapeutic use ; Positron-Emission Tomography ; Triazoles/*therapeutic use ; }, abstract = {A 55-year-old woman visited our clinic for rapid swelling of her left breast. The left breast was palpated, and a mass of about 10 cm with thick skin, and multiple lymph nodes in the supraclavicle and axilla were found. PET-CT images showed an increased uptake in her left breast, lymph nodes, spine of TH5, sternum, left lobe of liver, and both lungs. The serum tumor markers were also found to be elevated. A core needle biopsy was performed, and the tumor was diagnosed as secondary inflammatory carcinoma (invasive ductal carcinoma). Immunohistochemical staining showed negative for HER2 protein, but strongly positive for ER and PgR. Letrozole monotherapy administered her starting June, 2008. After 3 months, the metastases showed a notable response, which was subsequently maintained for 19 months. The tumor markers decreased to the normal range after 6 months, and the multiple metastases were not found by PET-CT after 1 year. A radiofrequency ablation operation was conducted on the remaining 3 cm breast cancer. Neoadjuvant endocrine therapy with letrozole was shown to be useful for post-menopausal breast cancer patients with strong hormone receptor expression.}, } @article {pmid21401208, year = {2011}, author = {Hill, JJ and Tremblay, TL and Pen, A and Li, J and Robotham, AC and Lenferink, AE and Wang, E and O'Connor-McCourt, M and Kelly, JF}, title = {Identification of vascular breast tumor markers by laser capture microdissection and label-free LC-MS.}, journal = {Journal of proteome research}, volume = {10}, number = {5}, pages = {2479-2493}, doi = {10.1021/pr101267k}, pmid = {21401208}, issn = {1535-3907}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Blotting, Western ; Breast Neoplasms/*blood supply/*metabolism ; Carcinoma, Ductal, Breast/*blood supply/*metabolism ; Chromatography, Liquid ; Computational Biology ; Female ; Humans ; Microarray Analysis ; Microdissection ; Microscopy, Fluorescence ; Microvessels/*metabolism ; Middle Aged ; Proteomics/*methods ; Tandem Mass Spectrometry ; }, abstract = {Blood vessels in tumors frequently show abnormal characteristics, such as tortuous morphology or leakiness, but very little is known about protein expression in tumor vessels. In this study, we have used laser capture microdissection (LCM) to isolate microvessels from clinical samples of invasive ductal carcinoma (IDC), the most common form of malignant breast cancer, and from patient-matched adjacent nonmalignant tissue. This approach eliminates many of the problems associated with the heterogeneity of clinical tumor tissues by controlling for differences in protein expression between both individual patients and different cell types. Proteins from the microvessels were trypsinized and the resulting peptides were quantified by a label-free nanoLC-MS method. A total of 86 proteins were identified that are overexpressed in tumor vessels relative to vessels isolated from the adjacent nonmalignant tissue. These proteins include well-known breast tumor markers such as Periostin and Tenascin C but also proteins with lesser-known or emerging roles in breast cancer and tumor angiogenesis (i.e., Serpin H1, Clic-1, and Transgelin 2). We also identified 40 proteins that were relatively under-expressed in IDC tumor vessels, including several components of the basement membrane whose lower expression could be responsible for weakening tumor vessels. Lastly, we show that a subset of 29 proteins, derived from our list of differentially expressed proteins, is able to predict survival in three publicly available clinical breast cancer microarray data sets, which suggests that this subset of proteins likely plays a functional role in cancer progression and outcome.}, } @article {pmid21398053, year = {2012}, author = {Yu, E and Suzuki, H and Younus, J and Elfiki, T and Stitt, L and Yau, G and Vujovic, O and Perera, F and Lock, M and Tai, P}, title = {The impact of post-mastectomy radiation therapy on male breast cancer patients--a case series.}, journal = {International journal of radiation oncology, biology, physics}, volume = {82}, number = {2}, pages = {696-700}, doi = {10.1016/j.ijrobp.2011.01.010}, pmid = {21398053}, issn = {1879-355X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/mortality/pathology/prevention & control/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/mortality/pathology/*radiotherapy/surgery ; Disease-Free Survival ; Dose Fractionation, Radiation ; Follow-Up Studies ; Humans ; Male ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/mortality/prevention & control ; Neoplasm Staging ; Postoperative Care ; }, abstract = {OBJECTIVE: To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP).

METHODS AND MATERIALS: Men with a diagnosis of breast cancer referred to LRCP were reviewed. The seventh American Joint Committee on Cancer staging system was used. Patients treated with and without post-mastectomy radiation therapy (PMRT) were analyzed. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. Survival estimates were obtained using Kaplan-Meier methodology.

RESULTS: From January 1977 to December 2006, 81 men had invasive ductal carcinoma. The median age was 65 (range, 35-87 years). There were 15 Stage I, 40 Stage II, 20 Stage III, and 6 Stage IV patients. Median follow-up time was 46 months (range, 1-225 months). Of the 75 patients treated with curative intent, 29 did not receive PMRT and 46 completed PMRT. Patients who received PMRT demonstrated no benefit in overall survival (p = 0.872) but significantly better local recurrence free survival (p < 0.001) compared with those who did not receive RT. There was trend toward improving locoregional recurrence with PMRT in patients with high-risk features (node-positive, advanced stage, and ≤ 2 mm or unknown surgical margin). The median, 5-year, and 10-year disease-free survival and overall survival for the 75 patients were 77.7 months, 66.3%, 32.7%, and 91.2 months, 73.9%, and 36.6%, respectively.

CONCLUSION: The experience at LRCP suggests that high-risk MBC patients should consider PMRT to improve their chance of local recurrence-free survival.}, } @article {pmid21390905, year = {2011}, author = {Mikulincer, M and Shaver, PR and Avihou-Kanza, N}, title = {Individual differences in adult attachment are systematically related to dream narratives.}, journal = {Attachment & human development}, volume = {13}, number = {2}, pages = {105-123}, doi = {10.1080/14616734.2011.553918}, pmid = {21390905}, issn = {1469-2988}, mesh = {Adult ; Affect ; Age Factors ; Anxiety/*psychology ; Conflict, Psychological ; Consciousness ; Dreams/*psychology ; Female ; Humans ; Male ; Models, Psychological ; Motivation ; Narration ; *Object Attachment ; Psychometrics ; Self Report ; Statistics as Topic ; *Unconscious, Psychology ; Young Adult ; }, abstract = {Self-reported individual differences in attachment insecurities (anxiety and avoidance) are sometimes assumed to tap only conscious mental processes, although many studies have found correlations between such measures and responses to the Thematic Apperception Test, the Rorschach Inkblot Test, and diverse laboratory measures of unconscious mental processes. Dreams offer another route into the unconscious, as Freud famously claimed: a route found useful in psychotherapy. In this study, approximately 1000 dreams reported by 68 young adults who kept dream diaries for a month were analyzed using the Core Conflictual Relationships Theme method, and the themes were examined in relation to (a) scores on the Experiences in Close Relationships measure of attachment anxiety and avoidance and (b) stress experienced the day before each dream. In line with attachment theory and previous research, attachment-related avoidance predicted avoidant wishes and negative representations of other people in dreams. Attachment anxiety predicted wishes for interpersonal closeness, especially in dreams following stressful days, and negative representations of self and both positive and negative representations of others, with negative representations being more common in dreams following stressful days.}, } @article {pmid21382187, year = {2011}, author = {Taylor, D and Lazberger, J and Ives, A and Wylie, E and Saunders, C}, title = {Reducing delay in the diagnosis of pregnancy-associated breast cancer: how imaging can help us.}, journal = {Journal of medical imaging and radiation oncology}, volume = {55}, number = {1}, pages = {33-42}, doi = {10.1111/j.1754-9485.2010.02227.x}, pmid = {21382187}, issn = {1754-9485}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*diagnostic imaging ; Early Diagnosis ; Female ; Humans ; Mass Screening/*methods ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnostic imaging ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors ; Ultrasonography, Mammary/*methods ; Waiting Lists ; }, abstract = {INTRODUCTION: The evaluation of breast symptoms during pregnancy or lactation can be challenging but prompt, appropriate assessment of symptoms may lead to earlier cancer detection.

METHODS: A review of breast imaging from 22 women with breast cancer during or within 1 year of pregnancy was undertaken as part of a large population-based study of gestational breast cancer. Consensus findings of three reads using the Breast Imaging Reporting and Data System lexicon were recorded.

RESULTS: The commonest presenting symptom was a lump. Diagnosis by percutaneous biopsy was made correctly in 21 of 23 lesions. Lesions were predominantly invasive ductal carcinoma (91%). One third had extensive associated ductal carcinoma in situ (DCIS). Ultrasound (US) was abnormal in all symptomatic patients. The most common sonographic finding was a solitary hypoechoic mass with irregular margins. 'Expanded stroma' with prominent ducts and architectural distortion was noted in three cases; all had extensive high-grade DCIS. In three women, bilateral breast US detected cancer in the asymptomatic breast. Mammography (performed in 86% of women) was abnormal in 74%, despite the presence of dense breast tissue in 47%. Widespread calcifications were visible in 26%, with detection of asymptomatic contra-lateral disease in one patient. MRI was performed in six patients. Background parenchymal enhancement did not impair lesion detection; however, overestimation of lesion size can occur.

CONCLUSIONS: Ultrasonography is recommended for the initial diagnosis of breast symptoms during pregnancy and lactation. A negative study should not delay direct fine needle aspiration of a palpable lesion. Mammography is indicated where initial assessment suggests malignancy. MRI may have a role in selected cases.}, } @article {pmid21377646, year = {2011}, author = {Fernandes, FP and Manlhiot, C and McCrindle, BW and Mertens, L and Kantor, PF and Friedberg, MK}, title = {Usefulness of mitral regurgitation as a marker of increased risk for death or cardiac transplantation in idiopathic dilated cardiomyopathy in children.}, journal = {The American journal of cardiology}, volume = {107}, number = {10}, pages = {1517-1521}, doi = {10.1016/j.amjcard.2011.01.030}, pmid = {21377646}, issn = {1879-1913}, mesh = {Cardiomyopathy, Dilated/drug therapy/*mortality/*surgery ; Child ; Echocardiography ; Female ; *Heart Transplantation ; Humans ; Male ; Mitral Valve Insufficiency/*complications/physiopathology ; Prognosis ; Retrospective Studies ; Risk Factors ; }, abstract = {In adults with idiopathic dilated cardiomyopathy (IDC), mitral regurgitation (MR) is associated with adverse prognosis and is often addressed by surgery or intervention. MR is commonly found in children with IDC, but its prognostic relevance has not been defined, and interventions to reduce MR are not routinely performed in this population. In this study, it was hypothesized that MR is an independent risk factor for death or transplantation. This was a single-center, retrospective study of sequential patients with IDC or familial IDC (left ventricular end-diastolic dimension z score >2 and ejection fraction <50%). Patients with acute myocarditis or previous mitral surgery were excluded. MR severity was graded according to American Society of Echocardiography guidelines as mild, moderate, or severe on the basis of MR jet vena contracta width. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were measured by biplane Simpson's method. Forty-two children with IDC were studied. The mean follow-up period was 25 months. At initial assessment, 34 children (82%) were taking angiotensin-converting enzyme inhibitors, 25 (60%) furosemide, 27 (65%) β blockers, and 7 (17%) intravenous inotropes. The mean indexed end-systolic volume was 91 ± 51 ml/m(2). The mean ejection fraction was 27 ± 16%. MR was mild in 42%, moderate in 19%, severe in 2%, and absent in 35% of patients. MR severity progressed from initial to last evaluation. MR severity was an independent risk factor for lower freedom from death or transplantation. Progression in MR severity increased the annual hazard of death or transplantation by a factor of 2.4 (p = 0.003). In conclusion, MR severity is independently associated with worse clinical status and decreased freedom from death or transplantation in children with IDC.}, } @article {pmid21375429, year = {2012}, author = {Zakout, YM and Abdullah, SM and Ali, MA}, title = {Assessment of elastosis in invasive ductal carcinoma of the breast compared to fibroadenoma among Sudanese patients using conventional histochemical methods.}, journal = {Biotechnic & histochemistry : official publication of the Biological Stain Commission}, volume = {87}, number = {2}, pages = {122-125}, doi = {10.3109/10520295.2011.565805}, pmid = {21375429}, issn = {1473-7760}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Connective Tissue Diseases/epidemiology/pathology ; Elastic Tissue/*pathology ; Female ; Fibroadenoma/*pathology ; Histocytochemistry ; Humans ; Sudan/epidemiology ; }, abstract = {We aimed to identify, using histochemical methods, the degree of elastosis in a malignant breast tumor compared to a benign tumor. Sixty-four tissue blocks were used in this study of which 34 (53.1%) were Invasive ductal carcinoma (IDC) (cases) and 30 (46.8%) were fibroadenomas (controls). Examination of Verhoeff's stained sections revealed different grades of elastosis in 29 (85.2%) cases compared to seven (23.3%) in controls. These findings indicated that elastosis was a prominent feature of IDC (p < 0.000). IDC was associated with more frequent occurrence of different grades of elastosis and should, therefore, be considered a valuable histological finding. Nevertheless, more advanced technology for quantitative measurements of the staining density is recommended to confirm this variation.}, } @article {pmid21371080, year = {2011}, author = {Logullo, AF and Stiepcich, MM and Osório, CA and Nonogaki, S and Pasini, FS and Rocha, RM and Soares, FA and Brentani, MM}, title = {Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma.}, journal = {Histopathology}, volume = {58}, number = {4}, pages = {617-625}, pmid = {21371080}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cohort Studies ; DNA-Binding Proteins/metabolism ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-fos/*metabolism ; Receptor, ErbB-2/metabolism ; Retrospective Studies ; Tissue Array Analysis ; Transcription Factor AP-1/metabolism ; Young Adult ; }, abstract = {AIMS: Fos-related antigen 1 (Fra-1) is a member of the activator protein 1 (AP-1) transcription factor family. Our objective was to evaluate the role of Fra-1 expression in breast carcinoma progression and prognosis.

METHODS AND RESULTS: Fra-1 expression was investigated by immunohistochemistry in two tissue microarrays containing, respectively, 85 ductal carcinoma in situ (DCIS) and 771 invasive ductal carcinoma (IDC) samples. Staining was observed in the nucleus and cytoplasm of the carcinomas, but only nuclear staining was considered to be positive. Fibroblasts associated with IDC were also Fra-1-positive. The frequency of Fra-1 positivity in IDC (22.8%) was lower than that in DCIS (42.2%). No association was found between Fra-1 and clinico-pathological variables in DCIS. In IDC, Fra-1 expression correlated with aggressive phenotype markers, including: high grade, oestrogen receptor negativity and human epidermal growth factor receptor 2 (HER-2) positivity (P=0.001, 0.015 and 0.004, respectively), and marginally with the presence of metastasis (P=0.07). Fra-1 was more frequently positive in basal-like (34%) and in HER-2-positive (38.5%) subtypes than in luminal subtypes. Fra-1 presence did not correlate with survival.

CONCLUSIONS: A high frequency of Fra-1 in DCIS tumours may be associated with early events in breast carcinogenesis. Although Fra-1 expression correlated with features of a more aggressive phenotype in IDC, no relationship with overall survival was found.}, } @article {pmid21371077, year = {2011}, author = {Yoshioka, T and Umekita, Y and Ohi, Y and Souda, M and Sagara, Y and Sagara, Y and Sagara, Y and Rai, Y and Tanimoto, A}, title = {Aldehyde dehydrogenase 1 expression is a predictor of poor prognosis in node-positive breast cancers: a long-term follow-up study.}, journal = {Histopathology}, volume = {58}, number = {4}, pages = {608-616}, doi = {10.1111/j.1365-2559.2011.03781.x}, pmid = {21371077}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase 1 Family ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*enzymology/mortality/pathology ; Carcinoma, Ductal, Breast/*enzymology/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/mortality/pathology ; Confidence Intervals ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Isoenzymes/*biosynthesis/metabolism ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retinal Dehydrogenase/*biosynthesis/metabolism ; Survival Rate ; Young Adult ; }, abstract = {AIMS: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells. The aim was to determine the prognostic significance of ALDH1 expression in a long-term follow-up study.

METHODS AND RESULTS: Immunohistochemical analyses were performed on 257 invasive ductal carcinomas (IDCs), 109 matched lymph node metastases and 190 ductal carcinomas in situ (DCISs), using paraffin-embedded sections. ALDH1 expression was found in 26% of IDCs, and correlated with larger tumour size (P=0.007), high histological grade (P<0.001), HER2 overexpression (P<0.001) and negative hormone receptor status (P<0.001). ALDH1 expression was observed in 14% of DCISs but was not correlated with any clinicopathological parameter. The IDC patients were followed up for 7-190 months (median: 120 months), and groups with ALDH1 expression had shorter relapse-free survival (P=0.0013) and overall survival (OS) (P=0.0005) by log-rank test. By Cox's multivariate analysis, it had a weak effect on OS (P=0.047), and its most significant effect on OS was observed in node-positive groups (P=0.013). No significant differences in OS stratified by ALDH1 expression status in lymph node metastases were noted.

CONCLUSIONS: ALDH1 expression in primary cancer is an independent prognostic factor in node-positive breast cancer patients.}, } @article {pmid21368500, year = {2011}, author = {Takamizawa, J and Kuze, S and Kyokane, T and Shibahara, H and Nakamura, H and Baba, S}, title = {[A case of pancreatic metastasis from breast cancer during multimodality therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {2}, pages = {301-303}, pmid = {21368500}, issn = {0385-0684}, mesh = {Biopsy ; Breast Neoplasms/*drug therapy/pathology ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/secondary ; Tomography Scanners, X-Ray Computed ; }, abstract = {We report a case of pancreatic metastasis from breast cancer during multimodality therapy. A 53-year-old woman received right breast-conserving surgery for invasive ductal carcinoma and then chemo-radiotherapy for liver, brain, bone, neck and axillary lymphnodes, mediastinum, pleural, and spinal cord metastasis. Although she then survived in a tumor-free condition, a blood examination performed 4 years after the surgery showed an elevated serum amylase level. Abdominal CT and US revealed swelling of the pancreas head and body with main pancreatic duct dilatation of the pancreatic tail. ERCP showed diffuse stenosis of the extrahepatic bile duct and the main pancreatic duct of the pancreatic head and body. Immunohistochemical staining of the biopsy specimen from the pancreatic head confirmed pancreatic metastasis from breast cancer. Despite the intensive chemotherapy including trastuzumab, she died 2 years after the onset of pancreatic metastasis. Metastatic breast cancer to the pancreas is very rare. However, considering the recent advances of multimodality therapy for breast cancer, this clinical state may become more common.}, } @article {pmid21368465, year = {2011}, author = {Kurozumi, S and Takeo, T and Ikeda, F and Horiguchi, J and Takeyoshi, I and Ito, H}, title = {[A case of aromatase inhibitor-tolerant metastatic breast cancer revealing complete remission with high-dose toremifene therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {38}, number = {1}, pages = {93-96}, pmid = {21368465}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Aromatase Inhibitors/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*drug therapy/pathology/surgery ; Drug Resistance, Neoplasm/*drug effects ; Female ; Humans ; Lymphatic Metastasis ; Remission Induction ; Toremifene/*therapeutic use ; }, abstract = {A 78-year-old woman diagnosed with left breast cancer (T2N1M0, Stage II B) was given breast-conserving therapy with axillary dissection. Pathological findings of the tumor were: 2.5 cm in size, invasive ductal carcinoma, nuclear grade 3, positive lymphatic invasion and pN1a. ER and PgR were both positive, and HER2 was negative. Administration of anastrozole (1 mg/day) and UFT (300 mg/day) was performed as adjuvant therapy for 8 months. However, several subcutaneous nodules appeared in the left breast and left axilla, after 11 months. Cytology and histology of nodules indicated metastatic invasive ductal carcinoma. We began high-dose toremifene therapy (120 mg/day) (HD-TOR) for treatment of recurrence and complete remission (CR), and was obtained after 8 months in all recurrent lesions. In this study, we demonstrated a case of aromatase inhibitor-tolerant metastatic breast cancer revealing CR following high-dose toremifene therapy.}, } @article {pmid21358084, year = {2010}, author = {Piroozmand, A and Hassan, ZM}, title = {Evaluation of natural killer cell activity in pre and post treated breast cancer patients.}, journal = {Journal of cancer research and therapeutics}, volume = {6}, number = {4}, pages = {478-481}, doi = {10.4103/0973-1482.77110}, pmid = {21358084}, issn = {1998-4138}, mesh = {Adult ; Breast Neoplasms/*immunology/surgery ; Carcinoma, Ductal, Breast/*immunology/surgery ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural/*immunology ; Mastectomy ; Middle Aged ; }, abstract = {AIM: To evaluate natural killer (NK) cells activity in breast cancer patients and its comparison with normal individuals.

SETTINGS AND DESIGN: Breast cancer is the most prevalent type of spontaneous tumor in humans, and NK cells are the first line defense against such tumors. There is a reverse correlation between NK activity and metastasis and reducing the tumor mass by surgery may be monitoring the NK activity. In this study, we evaluate NK activity in pre and post mastectomy patients.

MATERIALS AND METHODS: Eighteen patients with invasive ductal carcinoma attended to cancer research institute were included in this study. NK cells were evaluated in pre and post mastectomy patients. PBMCs were isolated by ficoll hypaque. NK cell activity (% lysis of K562) was evaluated by flow cytometer.

STATISTICAL ANALYSIS USED: One way analysis of variation (ANOVA) and Kruskal Wallis nonparametric test were employed using SPSS software.

RESULTS: While NK cell activity was greatly impaired in breast cancer patients (average lysis of K562 target cells: 24.4% vs. 62.5% in healthy controls, n = 18), it was found to be significantly increased after mastectomy (37.7%).

CONCLUSIONS: Mastectomy may lead to increased activity of NK cells among patients suffering from breast cancer and their increased activity may produce positive therapeutic effect.}, } @article {pmid21355660, year = {2011}, author = {Ein-Dor, T and Mikulincer, M and Shaver, PR}, title = {Attachment insecurities and the processing of threat-related information: Studying the schemas involved in insecure people's coping strategies.}, journal = {Journal of personality and social psychology}, volume = {101}, number = {1}, pages = {78-93}, doi = {10.1037/a0022503}, pmid = {21355660}, issn = {1939-1315}, mesh = {*Adaptation, Psychological ; Adult ; Anxiety/*psychology ; Arousal ; Avoidance Learning ; Character ; *Defense Mechanisms ; Fear ; Female ; Humans ; Male ; Middle Aged ; Models, Psychological ; Motivation ; *Object Attachment ; Reaction Time ; Reactive Attachment Disorder/*psychology ; Reinforcement Schedule ; *Self Concept ; Social Perception ; Social Support ; Young Adult ; }, abstract = {In 6 studies we examined procedural, scriptlike knowledge associated with 2 different kinds of attachment insecurity: anxiety and avoidance. The studies examined associations between attachment insecurities, the cognitive accessibility of sentinel and rapid fight-flight schemas, and the extent to which these schemas guide the processing of threat-related information and actual behavior during an experimentally induced threatening event. Anxious attachment was associated with (a) greater accessibility of the sentinel schema in narratives of threatening events; (b) faster, deeper, and more schema-biased processing of information about components of the sentinel schema; and (c) quicker detection of a threat. Avoidant attachment was associated with greater accessibility of the rapid fight-flight schema in narratives of threatening events and faster, deeper, and more schema-biased processing of information about components of the schema. We discuss implications of the findings for understanding the cognitive aspects of insecure people's coping strategies in threatening situations, as well as the potential benefits of these strategies to the people who enact them and to the groups to which they belong.}, } @article {pmid21352587, year = {2011}, author = {Richter, G and Uleer, C and Noesselt, T}, title = {Multifocal invasive ductal breast cancer with osteoclast-like giant cells: a case report.}, journal = {Journal of medical case reports}, volume = {5}, number = {}, pages = {85}, pmid = {21352587}, issn = {1752-1947}, abstract = {INTRODUCTION: To the best of our knowledge, this is the first case report of a multifocal (trifocal) invasive carcinoma of the breast containing osteoclast-like giant cells.

CASE PRESENTATION: A 64-year-old Caucasian woman presented for routine mammography screening with three radiodense lesions in the lower inner quadrant of the right breast, a primary breast cancer. Microscopic examination showed three foci of invasive ductal carcinoma with multinucleated osteoclast-like giant cells. Osteoclast-like giant cells in breast cancer are a rare phenomenon. They are described in less than two percent of all breast cancers and occur in association with invasive ductal cancer and invasive lobular cancer. In addition, osteoclast-like giant cells have been described in several sarcomas and metaplastic carcinomas of the breast.

CONCLUSION: To the best of our knowledge, this is the first report of a multifocal infiltrating ductal carcinoma of the breast containing osteoclast-like giant cells. This could be an indication for a possible early event in carcinogenesis associated with a biological event or secretion that indicates the differentiation and/or migration of stromal cells or macrophages.}, } @article {pmid21351127, year = {2011}, author = {Rovner, E and Kennelly, M and Schulte-Baukloh, H and Zhou, J and Haag-Molkenteller, C and Dasgupta, P}, title = {Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder.}, journal = {Neurourology and urodynamics}, volume = {30}, number = {4}, pages = {556-562}, doi = {10.1002/nau.21021}, pmid = {21351127}, issn = {1520-6777}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Botulinum Toxins, Type A/administration & dosage/*therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Humans ; Injections, Intramuscular ; Intention to Treat Analysis ; Male ; Middle Aged ; Patient Selection ; Treatment Outcome ; Urinary Bladder, Overactive/complications/*drug therapy ; Urinary Incontinence/complications/*drug therapy ; Urodynamics/drug effects ; }, abstract = {AIMS: We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics.

METHODS: Three hundred thirteen patients with OAB were randomized to double-blind intradetrusor injection with placebo (n = 44) or 1 of 5 onabotulinumtoxinA doses (50-300 U; n = 269). Primary efficacy variable was change from baseline in UUI episodes/week at week 12. Urodynamic assessments at baseline and weeks 12 and 36 included maximum cystometric capacity (MCC) and volume at first involuntary detrusor contraction (IDC).

RESULTS: 76.0% of patients had baseline DO. Changes from baseline in MCC and volume at first IDC with onabotulinumtoxinA ≥100 U were superior to placebo at week 12, generally decreasing by week 36. Significant dose-dependent increases in MCC were observed for all onabotulinumtoxinA doses at week 12, and for 150, 200, and 300 U at week 36. Data suggested a dose-response relationship. At week 12 on diary, 15.9% of placebo and 29.8-57.1% of onabotulinumtoxinA 50-300 U recipients, respectively, did not demonstrate UUI. OnabotulinumtoxinA doses >150 U were more commonly associated with post-void residual urine volumes >200 ml.

CONCLUSIONS: Improvements in urodynamic parameters and clinical outcomes generally trended together following onabotulinumtoxinA treatment. This therapy improved key urodynamic parameters in patients with idiopathic OAB and UUI, with no differences in outcomes between those with and those without baseline DO. Therefore, successful idiopathic OAB treatment with onabotulinumtoxinA does not appear to be related to pretreatment finding of DO.}, } @article {pmid21349659, year = {2011}, author = {Fouché, CJ and Tabareau, F and Michenet, P and Lebas, P and Simon, EG}, title = {[Specimen radiography assessment of surgical margins status in subclinical breast carcinoma: a diagnostic study].}, journal = {Journal de gynecologie, obstetrique et biologie de la reproduction}, volume = {40}, number = {4}, pages = {314-322}, doi = {10.1016/j.jgyn.2011.01.008}, pmid = {21349659}, issn = {1773-0430}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*pathology/surgery ; Female ; Humans ; Middle Aged ; Radiography ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {OBJECTIVE: This study aimed to determine the accuracy of specimen radiography in evaluating the surgical margins of impalpable breast carcinoma.

DESIGN AND SETTING: Retrospective study from June 2009 to June 2010 in Orleans Hospital Center.

PATIENTS AND METHODS: The study involved patients with impalpable in situ breast carcinoma diagnosed by mammography. Only patients with larger in situ carcinoma than invasive carcinoma were included. Patients underwent a breast conserving surgery after preoperative localization of the lesion.

PRIMARY ENDPOINT: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the specimen radiography are determined by correlation between radiologic and histologic margins.

RESULTS AND DISCUSSION: The following results were obtained from 46 patients: 36 DCIS cases (78%), six DCIS with IDC cases (13%), two LCIS cases (4%) and two biopsy suggested DCIS (4%). A radiologic margin of 2mm (by analogy with the histological margins) results in a NPV of 73%. NPV, sensibility and specificity were respectively 79, 60 and 74% for a radiologic margin of 5mm. The measure or inter-rater reliability found a moderate agreement (kappa: 0.62). The systematic review on this topic found only eight articles (small samples and only two prospective studies). We could not make any recommendations from the literature review on a threshold to define excision margin status.

CONCLUSION: The specimen radiography is a useful tool to assess margins of impalpable breast carcinoma. However, further studies are necessary as this point to determine a threshold for those radiologic margins.}, } @article {pmid21336547, year = {2011}, author = {Molyneux, G and Smalley, MJ}, title = {The cell of origin of BRCA1 mutation-associated breast cancer: a cautionary tale of gene expression profiling.}, journal = {Journal of mammary gland biology and neoplasia}, volume = {16}, number = {1}, pages = {51-55}, pmid = {21336547}, issn = {1573-7039}, mesh = {Animals ; BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics ; Female ; Gene Expression Profiling ; Genes, BRCA1 ; Humans ; Mice ; Microarray Analysis ; }, abstract = {Breast tumours are highly heterogeneous with several distinct sub-types recognised according to their histological and molecular features. The biological basis for this heterogeneity is largely unknown, although there are some distinct phenotype-genotype correlations. These include BRCA1 mutation-associated breast cancers, which are typically high grade invasive ductal carcinomas of no special type (IDC-NSTs) with pushing margins that do not express estrogen receptor (ER), progesterone receptor (PR) or the HER2 receptor tyrosine kinase ('triple negative'). Gene expression analysis of these tumours has grouped them with so called 'basal-like' breast cancers and this, together with evidence that knock-down of BRCA1 in vitro blocked luminal differentiation, led to speculation that these tumours arose from the normal basal stem cells within the mammary gland. Recently, however, human breast tissue from BRCA1 mutation carriers was shown to contain an expanded population of luminal progenitor cells which have increased in vitro clonogenic ability. In the mouse, targeted deletion of Brca1 in luminal ER negative progenitors resulted in the formation of mammary tumours which phenocopied human BRCA1 breast tumour pathology, while the deletion of Brca1 in basal stem cells resulted in the formation of tumours which neither resembled human BRCA1 tumours or sporadic basal-like breast tumours. Importantly, however, both sets of mouse tumours were classified as 'basal-like' by methods used for human tumour classification based on gene expression profiles. This demonstrates that, as it stands, expression profiling is poor at distinguishing tumour histological subtypes and is also a poor guide to the cell of tumour origin. These human and rodent studies support an origin of BRCA1-mutation associated breast cancer (and indeed of the majority of sporadic basal-like breast cancers) in a luminal ER negative mammary epithelial progenitor. This is a key finding, as identification of the cells of origin in breast cancer subtypes makes possible the identification of key processes associated with initiation, progression and maintenance of each tumour subtype, the development of novel targeted therapies and, potentially, of new preventative approaches in high risk groups.}, } @article {pmid21334720, year = {2011}, author = {Tian, Z and Wei, B and Tang, F and Wei, W and Gilcrease, MZ and Huo, L and Albarracin, CT and Resetkova, E and Middleton, L and Sahin, A and Xing, Y and Hunt, KK and Chen, J and Bu, H and Rashid, A and Abraham, SC and Wu, Y}, title = {Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation.}, journal = {Human pathology}, volume = {42}, number = {8}, pages = {1169-1177}, doi = {10.1016/j.humpath.2010.11.014}, pmid = {21334720}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/mortality/*pathology/surgery ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Carcinoma, Neuroendocrine/mortality/*secondary/surgery ; Cell Nucleus/pathology ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Survival Rate ; }, abstract = {Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.}, } @article {pmid21333994, year = {2011}, author = {Buttari, B and Profumo, E and Di Cristofano, C and Pietraforte, D and Lionetti, V and Capoano, R and Salvati, B and Businaro, R and Di Giammarco, G and Riganò, R}, title = {Haemoglobin triggers chemotaxis of human monocyte-derived dendritic cells: possible role in atherosclerotic lesion instability.}, journal = {Atherosclerosis}, volume = {215}, number = {2}, pages = {316-322}, doi = {10.1016/j.atherosclerosis.2010.12.032}, pmid = {21333994}, issn = {1879-1484}, mesh = {Actins/metabolism ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/immunology ; Cell Adhesion ; Chemotaxis, Leukocyte/*drug effects ; Dendritic Cells/*immunology ; Endothelial Cells ; Extracellular Signal-Regulated MAP Kinases/physiology ; Hemoglobins/metabolism/*pharmacology ; Humans ; Monocytes/cytology ; Plaque, Atherosclerotic/blood/physiopathology ; Receptors, Cell Surface/immunology ; Signal Transduction ; Transendothelial and Transepithelial Migration/*drug effects ; p38 Mitogen-Activated Protein Kinases/physiology ; }, abstract = {OBJECTIVE: Mechanisms that drive innate immune cell recruitment into atherosclerotic lesions are still not well defined. We tested the role of haemoglobin (Hb) to promote chemotaxis, adhesion to endothelial cells and transendothelial migration of human monocytes and monocyte-derived immature dendritic cells (iDCs) and its possible role in atherogenic cell recruitment.

METHODS AND RESULTS: We demonstrated that Hb triggers chemotaxis, adhesion to endothelial cells and transendothelial migration of monocytes and monocyte-derived iDCs. Innate immune cell chemotaxis significantly increased in the presence of Hb in a dose-dependent manner involving extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation and actin remodeling. The pre-treatment of cells with pre-titrated concentration of the anti-CD163 blocking antibody reduced the Hb-induced cell migration, thus suggesting the involvement of CD163 receptor. Conversely, N-acetyl cysteine and soluble Hb-scavenger protein haptoglobin (Hp) inhibited the Hb-induced iDC migration. Finally, spontaneous iDC migration significantly increased in the presence of serum of patients with haemorrhagic complicated plaques and partially decreased in the presence of Hp.

CONCLUSION: Hb by interacting with CD163 on monocytes and iDCs might induce cell recruitment and activation within vascular wall, thus contributing to the complex cross talk of chemotactic signals that mediate atherosclerotic lesions instability.}, } @article {pmid21326853, year = {2011}, author = {Hsiao, YH and Tsai, HD and Chou, MC and Man, YG}, title = {The myoepithelial cell layer may serve as a potential trigger factor for different outcomes of stage-matched invasive lobular and ductal breast cancers.}, journal = {International journal of biological sciences}, volume = {7}, number = {2}, pages = {147-153}, pmid = {21326853}, issn = {1449-2288}, support = {N02 PC051308/PC/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Epithelial Cells/*cytology/metabolism ; Female ; Humans ; Neoplasm Staging ; }, abstract = {Invasive lobular cancer (ILC) tends to be significantly larger in size with significantly more positive lymph nodes, whereas ILC has a significantly more favorable outcome, compared to stage-matched invasive ductal carcinoma (IDC). The mechanism accounting for such differences remains elusive. Based on morphological, immunohistochemical, and molecular studies of over 1,000 cases of human breast cancers, we hypothesize that the differences may result from the structural and/or functional differences of their surrounding myoepithelial cell layers, which dictate lobular and ductal tumor cells to follow different pathways of invasion or metastasis. The background, rationale, supportive data, and implications of our hypothesis are presented and discussed.}, } @article {pmid21325356, year = {2011}, author = {Zhang, X and Hanamura, N and Yamasita, M and Kashikura, Y and Ogawa, T and Taizo, S}, title = {A case of lobular carcinoma in situ presenting as a solid mass.}, journal = {The British journal of radiology}, volume = {84}, number = {999}, pages = {e48-50}, pmid = {21325356}, issn = {1748-880X}, mesh = {Breast Neoplasms/*diagnosis/surgery ; Carcinoma in Situ/*diagnosis/surgery ; Carcinoma, Lobular/*diagnosis/surgery ; Female ; Humans ; Middle Aged ; Sentinel Lymph Node Biopsy ; Treatment Outcome ; }, abstract = {A patient presented with a 2 cm lump in the lower outer quadrant of the left breast. Mammogram and ultrasonography showed a solid mass with a microlobulated contour, partially irregular border and microcalcifications. MRI showed an irregular mass with early enhancement and high signal intensity, and the late-phase image demonstrated a partial washout pattern. These findings suggest that the tumour was a malignant invasive carcinoma. Non-invasive ductal carcinoma was diagnosed after a fine needle aspiration and core needle biopsy followed by a partial breast excision and sentinel lymph node (SLN) biopsy. A pathological examination of the lesion displayed characteristic small monomorphic cells, solid proliferation and massive distension within the lobular unit. The tumour was immunohistochemically negative for E-cadherin and pure lobular carcinoma in situ (LCIS) was diagnosed. Pure LCIS is very rare and there have been no previous reports of pure LCIS forming a solid mass.}, } @article {pmid21321311, year = {2011}, author = {Chakravarty, G and Moroz, K and Makridakis, NM and Lloyd, SA and Galvez, SE and Canavello, PR and Lacey, MR and Agrawal, K and Mondal, D}, title = {Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {236}, number = {2}, pages = {145-155}, doi = {10.1258/ebm.2010.010086}, pmid = {21321311}, issn = {1535-3699}, mesh = {Biomarkers ; Breast Neoplasms/*diagnosis/*pathology/secondary ; Carcinoma, Ductal, Breast/*diagnosis/*pathology/secondary ; Cytoplasm/*enzymology ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Lymph Nodes/pathology ; Microarray Analysis ; Neoplasm Metastasis/diagnosis/pathology ; Prognosis ; SOX9 Transcription Factor/*metabolism ; Severity of Illness Index ; Survival Analysis ; }, abstract = {SOX9, a high mobility group (HMG) box transcription factor, is required for development, differentiation and lineage commitment. It is known to exert its effects through nuclear translocation, such as cell cycle changes in response to retinoic acid treatment in breast cancer cells. However, it is not known whether SOX9 has prognostic significance in human breast cancer. Over-expression and cytoplasmic sequestration of nuclear proteins are implicated in tumor progression. To determine whether SOX9 has any prognostic significance in human breast cancer, its expression and subcellular localization were analyzed in more than 200 human breast carcinomas (BCs). SOX9 mRNA expression data for human BCs were computed from microarray studies available in public databases and correlated with known poor prognostic parameters of BCs. SOX9 protein expression and its correlation with Ki-67 staining in human BCs were assessed using immunohistochemistry. Higher SOX9 mRNA levels were significantly associated with estrogen receptor negative (P ≤ 0.001) and higher grade (P ≤ 0.01) human breast tumors. Patients with higher SOX9 mRNA level had significantly shorter overall survival (P ≤ 0.0001). SOX9 protein, which is normally nuclear, was instead localized in the cytoplasm of 25-30% invasive ductal carcinomas (IDCs) and lymph node metastases. Its cytoplasmic accumulation significantly correlated with enhanced proliferation in breast tumors (Kendall's tau = 0.337 with a P value < 0.0001). Cytoplasmic SOX9 can serve as a valuable prognostic marker for IDCs and metastatic breast cancer. Its significant correlation with breast tumor cell proliferation implies that SOX9 directly contributes to the poor clinical outcomes associated with invasive breast cancer.}, } @article {pmid21317705, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Atypical tumor-stromal fibroblasts in invasive ductal carcinoma of the breast.}, journal = {The American journal of surgical pathology}, volume = {35}, number = {3}, pages = {325-336}, doi = {10.1097/PAS.0b013e31820afab9}, pmid = {21317705}, issn = {1532-0979}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Female ; Fibroblasts/*pathology ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Young Adult ; }, abstract = {Tumor-stromal fibroblasts have recently been reported to play important roles in the tumor progression of cancer in various organs. The purpose of this study was to investigate whether any characteristic histologic features of tumor-stromal fibroblasts could accurately predict the outcome of 1042 patients with invasive ductal carcinoma of the breast. We observed a small number of tumor-stromal fibroblasts with characteristic nuclear features existing inside and outside of fibrotic foci and named them atypical tumor-stromal fibroblasts. We then classified invasive ductal carcinomas into 4 types (1, 2, 3, and 4) according to the absence or presence of fibrotic foci and the absence or presence of atypical tumor-stromal fibroblasts. We then analyzed the outcome predictive powers of these types of invasive ductal carcinomas using multivariate analyses that included well-known clinicopathologic factors. The multivariate analyses showed that type 4 invasive ductal carcinomas with fibrotic foci and atypical tumor-stromal fibroblasts had significantly higher hazard ratios for tumor recurrence and tumor-related death, independent of the nodal status and histologic grade, and the type 2 invasive ductal carcinomas without fibrotic foci but with atypical tumor-stromal fibroblasts had a significant higher hazard ratio for tumor recurrence among patients with invasive ductal carcinoma with nodal metastasis and those with histologic grade 3 disease. The results of this study clearly indicated that the presence of atypical tumor-stromal fibroblasts, especially in fibrotic foci, is significantly associated with tumor recurrence and tumor-related death of patients with invasive ductal carcinoma of the breast.}, } @article {pmid21315415, year = {2011}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shimizu, C and Andoh, M and Fujiwara, Y and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {Atypical tumor-stromal fibroblasts in invasive ductal carcinomas of the breast treated with neoadjuvant therapy.}, journal = {Human pathology}, volume = {42}, number = {7}, pages = {998-1006}, doi = {10.1016/j.humpath.2010.10.020}, pmid = {21315415}, issn = {1532-8392}, mesh = {Adult ; Aged ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Female ; Fibroblasts/*pathology ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoadjuvant Therapy ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Tumor-stromal fibroblasts have recently been reported to play important roles in the tumor progression of cancer in various organs. The purpose of the present study was to investigate whether any characteristic histologic features of tumor-stromal fibroblasts could accurately predict the outcome of 318 patients with invasive ductal carcinoma of the breast who had received neoadjuvant therapy. We observed a small number of tumor-stromal fibroblasts with characteristic nuclear features existing in the tumor stroma and named these cells "atypical tumor-stromal fibroblasts." We then assessed the absence or presence of atypical tumor-stromal fibroblasts in biopsy (taken before neoadjuvant therapy) and surgical (taken after neoadjuvant therapy) materials and analyzed the outcome predictive powers of the presence of atypical tumor-stromal fibroblasts in biopsy and surgical materials using multivariate analyses that included well-known clinicopathological factors. The multivariate analyses demonstrated that the presence of atypical tumor-stromal fibroblasts assessed using biopsy materials had significantly higher hazard ratios for tumor recurrence and tumor-related death in patients with nodal metastasis and also significantly higher hazard ratios for tumor recurrence and tumor-related death independent of the hormone receptor status of the tumors. The results of this study clearly indicated that the presence of atypical tumor-stromal fibroblasts, especially in biopsy materials, is significantly associated with tumor recurrence and the tumor-related death of patients with invasive ductal carcinoma of the breast who have received neoadjuvant therapy.}, } @article {pmid21314937, year = {2011}, author = {Kretschmer, C and Sterner-Kock, A and Siedentopf, F and Schoenegg, W and Schlag, PM and Kemmner, W}, title = {Identification of early molecular markers for breast cancer.}, journal = {Molecular cancer}, volume = {10}, number = {1}, pages = {15}, pmid = {21314937}, issn = {1476-4598}, mesh = {Animals ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Mammary Neoplasms, Experimental/*diagnosis/metabolism/pathology ; Mice ; Microarray Analysis ; Neoplasm Invasiveness/diagnosis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore in silico analyses using an online microarray database were performed.

RESULTS: In DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry.

CONCLUSIONS: By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas.}, } @article {pmid21312071, year = {2012}, author = {Liang, H and Zhong, Y and Huang, Y and Chen, G}, title = {Type 1 receptor parathyroid hormone (PTH1R) influences breast cancer cell proliferation and apoptosis induced by high levels of glucose.}, journal = {Medical oncology (Northwood, London, England)}, volume = {29}, number = {2}, pages = {439-445}, pmid = {21312071}, issn = {1559-131X}, mesh = {Animals ; Apoptosis ; Blotting, Western ; Breast Neoplasms/complications/drug therapy/metabolism/*pathology ; Carcinoma, Ductal, Breast/complications/drug therapy/metabolism/*pathology ; Cell Proliferation ; Cohort Studies ; Diabetes Mellitus, Type 2/drug therapy/etiology/metabolism/*pathology ; Female ; Follow-Up Studies ; Glucose/*pharmacology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Rats ; Real-Time Polymerase Chain Reaction ; Receptor, Parathyroid Hormone, Type 1/antagonists & inhibitors/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Up-Regulation ; }, abstract = {Increased breast cancer incidence parallels the increase in cases of type 2 diabetes. We investigated the effect of type 1 receptor parathyroid hormone (PTH1R) expression on viability and apoptosis of breast cancer cells exposed to high levels of glucose. Upregulation of PTH1R was detected in patients with invasive ductal carcinoma of the breast and diabetes. In vitro, PTH1R silencing suppressed cell proliferation and apoptosis induced by high levels of glucose by regulating Bax/Bcl-2 expression. These results suggest PTH1R silencing may represent a novel treatment approach for patients diagnosed with invasive ductal carcinoma of the breast who are also managing diabetes.}, } @article {pmid21310570, year = {2012}, author = {Seror, JY and Lesieur, B and Scheuer-Niro, B and Zerat, L and Rouzier, R and Uzan, S}, title = {Predictive factors for complete excision and underestimation of one-pass en bloc excision of non-palpable breast lesions with the Intact(®) breast lesion excision system.}, journal = {European journal of radiology}, volume = {81}, number = {4}, pages = {719-724}, doi = {10.1016/j.ejrad.2011.01.049}, pmid = {21310570}, issn = {1872-7727}, mesh = {Biopsy/*instrumentation ; Breast Neoplasms/diagnostic imaging/*pathology ; Catheter Ablation/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Prognosis ; Radiography, Interventional/*instrumentation ; Reproducibility of Results ; Sensitivity and Specificity ; Stereotaxic Techniques/*instrumentation ; }, abstract = {OBJECTIVE: Image-guided percutaneous biopsy is the recommended initial diagnostic procedure for suspicious mammographic lesions. This study was conducted to determine the accuracy of the Intact(®) breast lesion excision system (BLES) and to identify predictive factors for complete excision and underestimation.

MATERIAL AND METHODS: A prospective study was conducted between January 28, 2008 and April 30, 2009 on 166 biopsy procedures using Intact(®) biopsy device. Diagnoses obtained from biopsy specimen were compared with to final diagnosis on surgical excision specimen.

RESULTS: Of the 166 patients, 15 (9%) displayed lesions with cell atypia, 28 (17%) had an intra ductal carcinoma (IDC) and 9 (5%) had an invasive carcinoma. Eight of 15 patients with cell atypia had open surgical excision, and none showed underestimation. All patients with IDC underwent surgical excision: we found an invasive carcinoma in 6 cases (21.4% underestimation) and a complete removal of the lesion by the Intact(®) BLES in 11 cases (39%). All 9 patients with invasive carcinoma had a surgical excision, with 1 complete removal of the lesion by Intact(®) BLES. Multivariate analyses did not identify predictive factors for underestimation; clear margins ≥1mm on biopsy specimen was the only independent predictive factor of complete excision (OR=8.51, p=0.02).

CONCLUSIONS: Intact(®) BLES provides a safe alternative to vacuum assisted core needle biopsy (VACNB) with an underestimation rate comparable to those previously reported for VACNB. The high rate of complete removal of the lesions, particularly ISC, offers an interesting perspective of avoiding subsequent excisional surgery for small lesions and thus requires further confirmational study.}, } @article {pmid21299347, year = {2011}, author = {Lü, X and Xu, K and Lü, H and Yin, Y and Ma, C and Liu, Y and Li, H and Suo, Z}, title = {CD44(+)/CD24(-) cells are transit progenitors and do not determine the molecular subtypes and clinical parameters in breast carcinomas.}, journal = {Ultrastructural pathology}, volume = {35}, number = {2}, pages = {72-78}, doi = {10.3109/01913123.2010.544843}, pmid = {21299347}, issn = {1521-0758}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*immunology/pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/*immunology/pathology ; Cell Line, Tumor ; Female ; Fibroadenoma/*immunology/pathology ; Humans ; Hyaluronan Receptors/*metabolism ; Immunohistochemistry ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Stem Cells/*immunology/pathology ; Phenotype ; }, abstract = {CD44(+)/CD24(-) cells have been associated with breast cancer stem/progenitor cell features. However, the status of this phenotype cells in normal, benign and malignant breast tissues has not been studied, and the clinical correlation of this subpopulation in breast cancer is not fully understood. The present study sought to identify these cells in a series of normal, benign, and malignant breast tissues and explore their correlation to the molecular subtypes of breast carcinoma and conventional pathological features. Double-staining immunohistochemistry (DIHC) of CD44 and CD24 was performed on 30 normal breast tissues, 30 breast fibroadenomas (FA), 60 breast invasive ductal carcinomas (IDC), and 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231). In the normal breast tissues and FAs, three phenotypes were observed including CD44(+)/CD24(+), CD44(+)/CD24(-), and CD44(-)/CD24(-) cells. In the IDCs, CD44(-)/CD24(+) cells were detected, in addition to the three aforementioned phenotypes. The strong positive rate (+++, incidence >60%) of CD44(+)/CD24(-) was significantly increased from normal breast tissue, FAs to IDCs (0.0%-->6.7%-->21.7%). However, the CD44(+)/CD24(-) cells didn't correlate with ages of patients, lymph node metastasis, tumor size, molecular subtypes, and the expression of ER, PR, HER-2, PS2, Bcl-2, nm23. The proportion of CD44(+)/CD24(-) cells in MCF-7, MDA-MB-468, and MDA-MB-231 was about 1, 5, and 80%, respectively. The results indicate that the CD44(+)/CD24(-) cells are transit progenitors and have no association with the molecular subtypes and clinicopathological parameters in the IDCs.}, } @article {pmid21299088, year = {2010}, author = {Aphinives, P and Punchai, S and Vajirodom, D and Bhudhisawasdi, V}, title = {Breast cancer: five-year survival in Srinagarind Hospital, Thailand.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {93 Suppl 3}, number = {}, pages = {S25-9}, pmid = {21299088}, issn = {0125-2208}, mesh = {Adult ; Breast Neoplasms/classification/diagnosis/*mortality/therapy ; Breast Neoplasms, Male/classification/diagnosis/*mortality/therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hospitals ; Humans ; Male ; Mastectomy ; Middle Aged ; Neoplasm Staging/*mortality ; Prognosis ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Survivors/*statistics & numerical data ; Thailand/epidemiology ; }, abstract = {BACKGROUND: Breast cancer is the second most common cancer among Thai women after cancer of the cervix.

OBJECTIVE: To investigate the overall five-year survival of breast cancer patients treated at Srinagarind hospital.

MATERIAL AND METHOD: Between January 1998 and December 2002, 382 patients with breast cancer who got definite treatment at Srinagarind hospital were included in the present study. Their medical records were reviewed including sex, age, stage at diagnosis, histological types, histological grades, treatment modality and survival.

RESULTS: There were 380 female patients (99.5%) and 2 male patients (0.5%). The peak age group was 41-50 years (38.5%), mean age was 48.3 years old. The most common histological type was invasive ductal carcinoma (95.3%). Most patients received surgical treatment (91.9%) and chemotherapy (94.2%). The overall five-year survival rate was 63%. The overall five-year survival rate in stage I, II, III and IV were 100%, 85%, 39% and 9% respectively.

CONCLUSION: The peak age of breast cancer was 41-50 years old. The overall five-year survival rate was 63%.}, } @article {pmid21297444, year = {2011}, author = {Singh, M and Mugler, K and Hailoo, DW and Burke, S and Nemesure, B and Torkko, K and Shroyer, KR}, title = {Differential expression of transferrin receptor (TfR) in a spectrum of normal to malignant breast tissues: implications for in situ and invasive carcinoma.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {19}, number = {5}, pages = {417-423}, doi = {10.1097/PAI.0b013e318209716e}, pmid = {21297444}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cells, Cultured ; Diagnosis, Differential ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Receptors, Transferrin/*metabolism ; Up-Regulation ; }, abstract = {Transferrin receptor (TfR), a type II transmembranous receptor involved in iron uptake, is highly expressed in some cancers. We evaluated the expression of TfR in a spectrum of normal to malignant breast tissues to test the hypothesis that overexpression is associated with malignant transformation. Expression of TfR was studied by immunohistochemistry (CD71-Antibody, Thermo Fisher Scientific, Fremont, CA) for percent positive cells (%) and intensity of staining (0 to 3 score) in normal (n=127), benign (n=172), potentially premalignant and in-situ carcinoma (n=65), and invasive carcinoma (n=38). Normal and benign lesions had significantly lower TfR expression compared with premalignant lesions (atypical hyperplasia and carcinoma in situ) and invasive carcinoma (median %: 0, 10, 50, and 80, respectively; P<0.0001). TfR expression was higher in high-grade ductal carcinoma in situ (DCIS) than in other grades of DCIS (median %: 95 vs 55; P=0.02) and in high-grade invasive carcinoma. Among the latter, medullary carcinoma had the highest expression and there was a trend for invasive lobular carcinoma to have a higher expression than invasive ductal carcinoma. In invasive carcinoma cases, the proportion (%) of cells staining for TfR was inversely correlated with the percentage of estrogen receptor-positive cells, with a decreasing slope on linear regression models. In comparison, the relationship with progesterone receptor was not as well defined and linear regression models revealed close to a flat line. These data show that there is a differential expression of TfR in breast tissues with the highest expression in in-situ and invasive carcinoma and with aggressive phenotypes (higher grade DCIS and lower estrogen receptor positivity in invasive carcinomas). Further studies are indicated to determine whether TfR is an independently significant prognostic marker that may have potential as a therapeutic target in in-situ and invasive breast carcinoma.}, } @article {pmid21291532, year = {2011}, author = {Madeira, M and Mattar, A and Passos, RJ and Mora, CD and Mamede, LH and Kishino, VH and Torres, TZ and de Sá, AF and dos Santos, RE and Gebrim, LH}, title = {A case report of male breast cancer in a very young patient: what is changing?.}, journal = {World journal of surgical oncology}, volume = {9}, number = {}, pages = {16}, pmid = {21291532}, issn = {1477-7819}, mesh = {Adult ; Breast Neoplasms, Male/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Combined Modality Therapy ; Fatal Outcome ; Fertility ; Humans ; Male ; Mammography ; Risk Factors ; }, abstract = {Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities. The present study reported the case of a 25-year-old man who was diagnosed with an advanced invasive ductal carcinoma; however, he did not have any important risk factors. Even though more data is emerging about this disease, more efforts to understand risk factors, treatment options and survival benefits are needed. In this case, we discussed the risk factors as well as the impaired fertility associated with breast cancer therapies.}, } @article {pmid21289526, year = {2011}, author = {Shimada, K and Nara, S and Esaki, M and Sakamoto, Y and Kosuge, T and Hiraoka, N}, title = {Intrapancreatic nerve invasion as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {40}, number = {3}, pages = {464-468}, doi = {10.1097/MPA.0b013e31820b5d37}, pmid = {21289526}, issn = {1536-4828}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/mortality/*pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neoplasm Recurrence, Local/pathology ; Pancreas/*innervation ; Pancreatic Neoplasms/mortality/*pathology/*surgery ; Pancreaticoduodenectomy ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Neural invasion is a distinct route for the spread of pancreatic carcinoma. However, the clinicopathologic significance of neural invasion, with particular reference to intrapancreatic nerve invasion, remains to be elucidated.

METHODS: One hundred fifty-three patients who underwent pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas between 2004 and 2008 were retrospectively examined. The clinical and histopathologic factors, including intrapancreatic nerve invasion, were analyzed in these patients. The relationships between the degree of intrapancreatic nerve invasion and disease-free survival, as well as various histopathologic factors, were investigated.

RESULTS: There were significant differences in the degree of intrapancreatic nerve invasion with regard to disease-free survival (P < 0.001). A lack of lymph node metastases (P = 0.001), lower incidence of intrapancreatic nerve invasion (P = 0.001), and negative surgical margin (P = 0.011) significantly increased the disease-free survival. The tumor stage was not associated with intrapancreatic nerve invasion (P = 0.255). However, a larger tumor size (P = 0.024), a higher incidence of lymphatic invasion (P = 0.036), and the presence of extrapancreatic nerve plexus invasion (P < 0.001) were identified as independent factors associated with a higher incidence of intrapancreatic nerve invasion.

CONCLUSIONS: Intrapancreatic nerve invasion may be useful as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas.}, } @article {pmid21289332, year = {2011}, author = {Zakharchenko, O and Greenwood, C and Lewandowska, A and Hellman, U and Alldridge, L and Souchelnytskyi, S}, title = {Meta-data analysis as a strategy to evaluate individual and common features of proteomic changes in breast cancer.}, journal = {Cancer genomics & proteomics}, volume = {8}, number = {1}, pages = {1-14}, pmid = {21289332}, issn = {1790-6245}, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Down-Regulation ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Metabolic Networks and Pathways/genetics ; Neoplasm Invasiveness ; *Proteomics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Tumor Suppressor Protein p53/genetics ; Up-Regulation ; }, abstract = {BACKGROUND: Individual differences among breast tumours in patients is a significant challenge for the treatment of breast cancer. This study reports a strategy to assess these individual differences and the common regulatory mechanisms that may underlie breast tumourigenesis.

MATERIALS AND METHODS: The two-step strategy was based firstly on a full-scale proteomics analysis of individual cases, and secondly on the analysis of common features of the individual proteome-centred networks (meta-data).

RESULTS: Proteomic profiling of human invasive ductal carcinoma tumours was performed and each case was analysed individually. Analysis of primary datasets for common cancer-related proteins identified keratins. Analysis of individual networks built with identified proteins predicted features and regulatory mechanisms involved in each individual case. Validation of these findings by immunohistochemistry confirmed the predicted deregulation of expression of CK2α, PDGFRα, PYK and p53 proteins.

CONCLUSION: Meta-data analysis allowed efficient evaluation of both individual and common features of the breast cancer proteome.}, } @article {pmid21287591, year = {2011}, author = {Sigmund, EE and Cho, GY and Kim, S and Finn, M and Moccaldi, M and Jensen, JH and Sodickson, DK and Goldberg, JD and Formenti, S and Moy, L}, title = {Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer.}, journal = {Magnetic resonance in medicine}, volume = {65}, number = {5}, pages = {1437-1447}, pmid = {21287591}, issn = {1522-2594}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; P30 CA 16087/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*pathology ; Contrast Media ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Gadolinium DTPA ; Humans ; Middle Aged ; Movement ; Neovascularization, Pathologic/pathology ; Software ; }, abstract = {Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t)), perfusion fraction (f(p)), and pseudodiffusivity (D(p)). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (±standard deviation) values (2.44 ± 0.30 vs. 1.34 ± 0.39 μm(2)/msec, P < 0.01) and D(t) (2.36 ± 0.38 vs. 1.15 ± 0.35 μm(2)/msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 ± 5.0% vs. 6.9 ± 2.9%, P = 0.06), but less so with D(t) (1.14 ± 0.32 μm(2)/msec vs. 1.18 ± 0.52 μm(2)/msec, P = 0.88) and D(p) (14.9 ± 11.4 μm(2)/msec vs. 16.1 ± 5.7 μm(2)/msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors.}, } @article {pmid21287362, year = {2011}, author = {Bae, SY and Lee, SK and Koo, MY and Hur, SM and Choi, MY and Cho, DH and Kim, S and Choe, JH and Lee, JE and Kim, JH and Kim, JS and Nam, SJ and Yang, JH}, title = {The prognoses of metaplastic breast cancer patients compared to those of triple-negative breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {126}, number = {2}, pages = {471-478}, doi = {10.1007/s10549-011-1359-8}, pmid = {21287362}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/*diagnosis/metabolism/therapy ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/therapy ; Disease-Free Survival ; ErbB Receptors/metabolism ; Female ; Humans ; Keratins/metabolism ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis ; Middle Aged ; Mixed Tumor, Malignant/*diagnosis/metabolism/therapy ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Metaplastic breast carcinoma (MBC) is a rare, heterogeneous breast cancer characterized by admixture of adenocarcinoma with metaplastic elements, low hormone receptor expression, and poor outcomes. The authors retrospectively reviewed the medical records of 47 MBC patients and 1,346 invasive ductal carcinoma (IDC) patients. Two hundred eighteen of the IDC patients were triple-negative (TN-IDC) for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (ER-/PR-/HER2-). Patients were surgically treated at the Samsung Medical Center between 2005 and 2009. The MBC patients presented with a larger tumor size, lower lymph node involvement, higher histological and nuclear grades, higher triple negativity (ER-/PR-/HER2-) and higher p53, CK5/6, and EGFR expressions compared with those of the IDC group. However, there were no significant differences in clinicopathological characteristics between MBC and TN-IDC. During the follow-up period (median duration of 30.3 months, range 2.6-56.3 months), seven (14.9%) MBC patients, and 98 (7.1%) IDC patients had disease recurrence. The three-year disease-free survival (DFS) rate was 78.1% in the MBC group and 91.1% in IDC group (P < 0.001). The three-year DFS rate was not significantly different between the MBC and TN-IDC groups (78.1 vs. 84.9%, P = 0.114). However, in patients with lymph node metastasis who underwent adjuvant chemotherapy, the three-year DFS rate was 44.4% in the MBC group and 72.5% in the TN-IDC group (P = 0.025). The authors found that MBC had a poorer clinical outcome than did IDC. In breast cancer patients with nodal metastasis, MBC had a poorer prognosis than did TN-IDC, despite adjuvant chemotherapy.}, } @article {pmid21287281, year = {2011}, author = {Bagaria, SP and Shamonki, J and Kinnaird, M and Ray, PS and Giuliano, AE}, title = {The florid subtype of lobular carcinoma in situ: marker or precursor for invasive lobular carcinoma?.}, journal = {Annals of surgical oncology}, volume = {18}, number = {7}, pages = {1845-1851}, doi = {10.1245/s10434-011-1563-0}, pmid = {21287281}, issn = {1534-4681}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/classification/*diagnosis/metabolism ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/classification/*diagnosis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/classification/*diagnosis/metabolism ; Carcinoma, Lobular/classification/*diagnosis/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {BACKGROUND: Lobular carcinoma in situ (LCIS) is considered a risk factor-not a precursor-for both invasive lobular and ductal carcinoma. Florid LCIS (F-LCIS) is an architectural subtype of LCIS that does not express E-cadherin, yet has the histologic and often radiographic appearance of solid-type ductal carcinoma in situ (DCIS). Since DCIS is considered a precursor to invasive ductal carcinoma, should F-LCIS be considered a precursor to invasive lobular carcinoma (ILC)?

METHODS: Review of an institutional database identified cases of LCIS and solid-type DCIS diagnosed by excisional biopsy, segmentectomy, or mastectomy between 1991 and 2000 to determine the prevalence of associated invasive breast cancer. Archival specimens were evaluated for florid and nonflorid LCIS, nuclear grade of LCIS, and the presence and subtype of invasive breast cancer. Solid-type DCIS that lacked E-cadherin expression was classified as F-LCIS.

RESULTS: Of 210 consecutive specimens of LCIS examined, 171 had nonflorid LCIS (81%) and 39 had F-LCIS (19%). Nonflorid LCIS had a diffuse pattern, whereas F-LCIS appeared as discrete foci adjacent to ILC. An invasive component was identified with 87% of F-LCIS lesions versus 73% of nonflorid LCIS lesions (P = 0.064); this component was lobular in 100% of F-LCIS lesions versus 82% of nonflorid LCIS lesions, a significant difference (P = 0.0044) that persisted when the analysis was adjusted for nuclear grade (P = 0.0082).

CONCLUSION: Its close spatial relationship to an invasive component and increased association with ILC suggest that F-LCIS may be a precursor for ILC.}, } @article {pmid21284437, year = {2011}, author = {Roy, I and Othieno, E}, title = {Breast carcinoma in Uganda: microscopic study and receptor profile of 45 cases.}, journal = {Archives of pathology & laboratory medicine}, volume = {135}, number = {2}, pages = {194-199}, doi = {10.5858/2008-0421-SOR1.1}, pmid = {21284437}, issn = {1543-2165}, mesh = {Adult ; Age Factors ; Age of Onset ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Uganda ; }, abstract = {CONTEXT: Histologic and receptor data on breast carcinoma in Uganda are scarce. Estrogen receptor status is not routinely available. Breast cancer blocks from Uganda were studied in Montreal, Canada, and clinical correlations subsequently discussed in Kampala, Uganda.

OBJECTIVE: To correlate histologic features (tumor type, histologic grade), receptor profile (estrogen receptor, progesterone receptor, and HER2/neu), and age in Ugandan women.

DESIGN: Pathology reports for 2000-2004 from Nsambya Hospital, reporting invasive breast carcinoma, provided 45 microscopically confirmed cases.

RESULTS: Seventy-three percent of patients were 50 years or younger. Histologic types were invasive ductal carcinoma (78%) and "good" prognosis types (11%). Overall 40% were grade 3, but 48% of invasive ductal carcinomas were grade 3. Estrogen receptor was positive in 60% overall and in 51% of invasive ductal carcinomas. HER2/neu was overexpressed in 11%; 36% were "triple" negative (estrogen receptor, progesterone receptor, HER2/neu negative).

CONCLUSIONS: Breast carcinoma in Ugandan women presents at a younger age and is histologically and by receptor profile more aggressive than carcinoma in Caucasian women.}, } @article {pmid21255198, year = {2011}, author = {Barone, P}, title = {Treatment of depressive symptoms in Parkinson's disease.}, journal = {European journal of neurology}, volume = {18 Suppl 1}, number = {}, pages = {11-15}, doi = {10.1111/j.1468-1331.2010.03325.x}, pmid = {21255198}, issn = {1468-1331}, mesh = {Antidepressive Agents, Tricyclic/*therapeutic use ; Antiparkinson Agents/*therapeutic use ; Benzothiazoles/therapeutic use ; Depression/complications/*drug therapy ; Desipramine/therapeutic use ; Dopamine Agonists/*therapeutic use ; Humans ; Levodopa/therapeutic use ; Nortriptyline/therapeutic use ; Parkinson Disease/complications/*drug therapy ; Pramipexole ; Randomized Controlled Trials as Topic ; Selective Serotonin Reuptake Inhibitors/*therapeutic use ; Sertraline/therapeutic use ; }, abstract = {Significant depressive disorders are present in approximately 30-40% of patients with Parkinson's disease (PD). Depressive symptoms are correlated with poor health-related quality-of-life (HRQoL) scores, and are the major determinant of HRQoL. Studies that have evaluated pharmacotherapy for depressive symptoms in PD have shown that there is substantial variability in outcomes. Recently, two double-blind, placebo-controlled studies showed the superiority of nortriptyline and desipramine versus placebo and selective serotonin reuptake inhibitors. The antidepressant effects of dopamine agonists have been explored mainly in open and non-controlled studies. In a 14-week randomized trial comparing pramipexole with sertraline in depressed patients without motor complications, the Hamilton Depression Rating Scale score decreased in both groups; however, in the pramipexole group, the proportion of patients who recovered was significantly higher. Recently, in the first 12-week double-blind placebo-controlled clinical trial in PD patients without motor fluctuations on stable levodopa treatment, pramipexole reduced depressive symptoms as measured by Beck Depression Inventory score, with a significant difference in efficacy in favour of pramipexole. These data suggest that pramipexole might represent an alternative to antidepressant drugs to treat depressive symptoms in PD without adding the risk of antidepressant adverse events, and avoid polypharmacy.}, } @article {pmid21273586, year = {2011}, author = {Buhmeida, A and Al-Maghrabi, J and Merdad, A and Al-Thubaity, F and Chaudhary, A and Gari, M and Abuzenadah, A and Collan, Y and Syrjänen, K and Al-Qahtani, M}, title = {Prognostic value of mitotic counts in breast cancer of Saudi Arabian patients.}, journal = {Anticancer research}, volume = {31}, number = {1}, pages = {97-103}, pmid = {21273586}, issn = {1791-7530}, mesh = {Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes/pathology ; Middle Aged ; *Mitotic Index ; Prognosis ; Saudi Arabia ; Survival Rate ; }, abstract = {BACKGROUND: Quantitative methods in combination with other objective prognostic criteria can improve the evaluation of a cancer patient's prognosis, and possibly predict response to therapy. One of the important prognostic and predictive markers is the mitotic count, which has proven valuable in many aspects. In this study, the prognostic value of the mitotic count was assessed in breast cancer (BC) patients in Saudi Arabia.

PATIENTS AND METHODS: The study comprised a series of 87 patients diagnosed and treated for breast cancer at the Departments of Surgery and Oncology, King Abdul-Aziz University Hospital, between 2000 and 2008. Mitotic counts were carried out using a standard laboratory microscope (objective, × 40; field diameter, 420 μm). The number of mitotic figures in 10 consecutive high-power fields (hpf) from the most cellular area of the sample gave the mitotic activity index (MAI, mitotic figures/10 hpf). The standardized mitotic index (SMI) recorded the mitotic count as the number of mitotic figures by area of the neoplastic tissue in the microscopic field, thus the number of mitoses in 10 consecutive fields was corrected for the volume fraction and field size (mitotic figures/mm²).

RESULTS: The means of MAI and SMI of the tumors in the entire series of 87 patients were 15 mitotic figures/10 hpf (range 4-45) and 4 mitotic figures/mm² (range 1-9), respectively. The mitotic counts were higher in advanced stages than in early cancer (p < 0.04). The mitotic counts were significantly larger in patients with high-grade tumor (p < 0.004) and in cases with tumor metastasis (p < 0.004). The mitotic counts were also significantly larger in the recurrent cases than in non-recurrent ones (p < 0.02).

CONCLUSION: The quantitatively measurable mitotic counts of cancer cell nuclei are of significant prognostic value in invasive ductal carcinoma of the breast in Saudi Arabia and the mean cut-off values of MAI and SMI can be applied as objective (quantitative) criteria to distinguish breast cancer patients into groups with favorable and less favorable prognosis.}, } @article {pmid21266630, year = {2011}, author = {Kramer, F and Schippert, C and Rinnau, F and Hillemanns, P and Park-Simon, TW}, title = {The First Description of Docetaxel-Induced Recall Inflammatory Skin Reaction After Previous Drug Extravasation.}, journal = {The Annals of pharmacotherapy}, volume = {45}, number = {2}, pages = {e11}, doi = {10.1345/aph.1P440}, pmid = {21266630}, issn = {1542-6270}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/drug therapy ; Carboplatin/administration & dosage ; Carcinoma, Ductal, Breast/drug therapy ; Docetaxel ; Drug Eruptions/*etiology ; Erythema/*chemically induced ; Extravasation of Diagnostic and Therapeutic Materials ; Female ; Humans ; Neoplasm Metastasis ; Recurrence ; Taxoids/administration & dosage/*adverse effects ; }, abstract = {OBJECTIVE: To describe a cutaneous recall soft tissue injury at the site of previous extravasation of docetaxel.

CASE SUMMARY: A 65-year-old white female with an invasive ductal carcinoma of the right breast was treated with carboplatin AUC 2 and docetaxel 30 mg/m(2) weekly via a peripheral vein access. During the 14th cycle, drug extravasation of docetaxel occurred in the left antecubital fossa characterized by a mild erythema without edema. A severe erythema developed in the former area of extravasation after the 15th cycle of carboplatin/docetaxel. The recall dermatitis continued to exacerbate after each course of systemic docetaxel chemotherapy and finally led to termination of this therapy.

DISCUSSION: In general, extravasation of docetaxel causes only mild local skin reactions without further necessity of intervention. For pegylated liposomal doxorubicin and paclitaxel, inflammatory recall phenomena at sites of previous drug extravasation are rare and often occur as single events following administration of the same cytotoxic drug. According to the Naranjo probability scale, the administration of docetaxel in this case probably led to the cutaneous soft tissue injury as a result of extravasation.

CONCLUSIONS: Caution is needed after an episode of docetaxel extravasation. Even after a therapy interruption of several weeks, resumption of chemotherapy with docetaxel might lead to recrudescence of the inflammatory skin reaction.}, } @article {pmid21266359, year = {2011}, author = {Zhang, L and Sullivan, PS and Goodman, JC and Gunaratne, PH and Marchetti, D}, title = {MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase.}, journal = {Cancer research}, volume = {71}, number = {3}, pages = {645-654}, pmid = {21266359}, issn = {1538-7445}, support = {2R01 CA086832-07/CA/NCI NIH HHS/United States ; P50CA58183/CA/NCI NIH HHS/United States ; R01 CA086832/CA/NCI NIH HHS/United States ; R01 CA086832-07/CA/NCI NIH HHS/United States ; R01 CA160335/CA/NCI NIH HHS/United States ; R01 CA216991/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Brain Neoplasms/enzymology/genetics/*secondary/*therapy ; Breast Neoplasms/enzymology/genetics/pathology/*therapy ; Cell Line, Tumor ; Down-Regulation ; Female ; Genetic Therapy ; Glucuronidase/biosynthesis/*genetics ; Humans ; Mice ; Mice, Nude ; MicroRNAs/*administration & dosage/genetics ; Molecular Targeted Therapy ; Neoplasm Invasiveness ; Transfection ; Xenograft Model Antitumor Assays ; }, abstract = {Heparanase (HPSE) is a potent protumorigenic, proangiogenic, and prometastatic enzyme that is overexpressed in brain metastatic breast cancer (BMBC). However, little is known about the regulation of this potential therapeutic target in BMBC, which remains very poorly managed in the clinic. We hypothesized that HPSE gene expression might be regulated by micro RNA that might be exploited therapeutically. Using miRanda and RNAhybrid, we identified miR-1258 as a candidate micro RNA that may directly target HPSE and suppress BMBC. In support of our hypothesis, we found that miR-1258 levels inversely correlated with heparanase expression, enzymatic activity, and cancer cell metastatic propensities, being lowest in highly aggressive BMBC cell variants compared with either nontumorigenic or nonmetastatic human mammary epithelial cells. These findings were validated by analyses of miR-1258 and heparanase content in paired clinical specimens of normal mammary gland versus invasive ductal carcinoma, and primary breast cancer versus BMBC. In regulatory experiments, miR-1258 inhibited the expression and activity of heparanase in BMBC cells, whereas modulating heparanase blocked the phenotypic effects of miR-1258. In functional experiments, stable expression of miR-1258 in BMBC cells inhibited heparanase in vitro cell invasion and experimental brain metastasis. Together, our findings illustrate how micro RNA mechanisms are linked to brain metastatic breast cancer through heparanase control, and they offer a strong rationale to develop heparanase-based therapeutics for treatment of cancer patients with brain metastases, BMBC in particular.}, } @article {pmid21264256, year = {2011}, author = {Morton, CO and Varga, JJ and Hornbach, A and Mezger, M and Sennefelder, H and Kneitz, S and Kurzai, O and Krappmann, S and Einsele, H and Nierman, WC and Rogers, TR and Loeffler, J}, title = {The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.}, journal = {PloS one}, volume = {6}, number = {1}, pages = {e16016}, pmid = {21264256}, issn = {1932-6203}, support = {1R21AI052236/AI/NIAID NIH HHS/United States ; }, mesh = {Aspergillus fumigatus/*genetics ; Cells, Cultured ; Dendritic Cells/*microbiology ; Gene Expression Regulation/*immunology ; Host-Pathogen Interactions/*genetics ; Humans ; Immune Evasion/genetics ; Inflammation/genetics ; Phagocytosis ; }, abstract = {Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes.}, } @article {pmid21250864, year = {2011}, author = {Flechsig, C and Suezer, Y and Kapp, M and Tan, SM and Löffler, J and Sutter, G and Einsele, H and Grigoleit, GU}, title = {Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells.}, journal = {Cytotherapy}, volume = {13}, number = {6}, pages = {739-752}, doi = {10.3109/14653249.2010.549123}, pmid = {21250864}, issn = {1477-2566}, mesh = {Antigen-Presenting Cells/immunology/metabolism ; Apoptosis ; Cell Survival ; Cells, Cultured ; Chemokine CXCL10/metabolism ; Cytokines/metabolism ; Dendritic Cells/*cytology/*immunology ; Humans ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Interleukin-6/metabolism ; Leukocytes, Mononuclear/cytology/*immunology/*virology ; Phagocytosis/immunology ; Receptors, CCR7/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cell Transplantation ; Transplantation, Homologous ; Tumor Necrosis Factor-alpha/metabolism ; Vaccinia virus/*physiology ; }, abstract = {BACKGROUND AIMS: Modified vaccinia Ankara (MVA) is a promising vaccine vector for infectious diseases and malignancies. It is fundamental to ascertain its tropism in human leukocyte populations and immunostimulatory mechanisms for application in immunotherapy.

METHODS: Human peripheral blood mononuclear cells (PBMC) and leukocyte subpopulations [monocyte-derived dendritic cells (DC), monocytes and B cells] were infected with MVA in order to evaluate their infection rate, changes in surface markers, cytokine expression and apoptosis.

RESULTS: Monocytes, DC and B cells were most susceptible to MVA infection, followed by natural killer (NK) cells. Monocytes were activated strongly, with upregulation of co-stimulatory molecules, major histocompatibility complex (MHC) molecules and chemokine (C-C motif) receptor (CCR7), while immature DC showed partial activation and B cells were inhibited. Furthermore, expression of chemokine (C-X-C motif) ligand (CXCL10), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p70 was enhanced but IL-1β and IL-10 were stable or even downregulated. MVA induced a high apoptosis rate of antigen-presenting cells (APC). Nevertheless, incubation of MVA-infected leukocytes with uninfected immature DC (iDC) led to complete maturation of the DC. Subsequently, the matured DC were able to stimulate cytomegalovirus (CMV)-immediate early protein (IE1)-specific T cells.

CONCLUSIONS: MVA induces a T-helper (Th)-1-polarizing cytokine expression in APC. Furthermore, incubation of MVA-infected leukocytes with uninfected iDC leads to complete maturation of the DC and may be the basis for cross-presentation of MVA-encoded antigens. Thus this approach seems to be an ideal model for further studies with MVA-encoded viral antigens regarding immunotherapy and vaccination strategies.}, } @article {pmid21248383, year = {2011}, author = {Sankarasubramanian, V and Buitenweg, JR and Holsheimer, J and Veltink, P}, title = {Electrode alignment of transverse tripoles using a percutaneous triple-lead approach in spinal cord stimulation.}, journal = {Journal of neural engineering}, volume = {8}, number = {1}, pages = {016010}, doi = {10.1088/1741-2560/8/1/016010}, pmid = {21248383}, issn = {1741-2552}, mesh = {Electric Stimulation Therapy/*instrumentation/methods ; *Electrodes ; Humans ; *Models, Neurological ; Pain/physiopathology ; Pain Management ; Spinal Cord/*physiology ; }, abstract = {The aim of this modeling study is to determine the influence of electrode alignment of transverse tripoles on the paresthesia coverage of the pain area in spinal cord stimulation, using a percutaneous triple-lead approach. Transverse tripoles, comprising a central cathode and two lateral anodes, were modeled on the low-thoracic vertebral region (T10-T12) using percutaneous triple-lead configurations, with the center lead on the spinal cord midline. The triple leads were oriented both aligned and staggered. In the staggered configuration, the anodes were offset either caudally (caudally staggered) or rostrally (rostrally staggered) with respect to the midline cathode. The transverse tripolar field steering with the aligned and staggered configurations enabled the estimation of dorsal column fiber thresholds (I(DC)) and dorsal root fiber thresholds (I(DR)) at various anodal current ratios. I(DC) and I(DR) were considerably higher for the aligned transverse tripoles as compared to the staggered transverse tripoles. The aligned transverse tripoles facilitated deeper penetration into the medial dorsal columns (DCs). The staggered transverse tripoles always enabled broad and bilateral DC activation, at the expense of mediolateral steerability. The largest DC recruited area was obtained with the rostrally staggered transverse tripole. Transverse tripolar geometries, using percutaneous leads, allow for selective targeting of either medial or lateral DC fibers, if and only if the transverse tripole is aligned. Steering of anodal currents between the lateral leads of the staggered transverse tripoles cannot target medially confined populations of DC fibers in the spinal cord. An aligned transverse tripolar configuration is strongly recommended, because of its ability to provide more post-operative flexibility than other configurations.}, } @article {pmid21244664, year = {2011}, author = {Krecsák, L and Micsik, T and Kiszler, G and Krenács, T and Szabó, D and Jónás, V and Császár, G and Czuni, L and Gurzó, P and Ficsor, L and Molnár, B}, title = {Technical note on the validation of a semi-automated image analysis software application for estrogen and progesterone receptor detection in breast cancer.}, journal = {Diagnostic pathology}, volume = {6}, number = {}, pages = {6}, pmid = {21244664}, issn = {1746-1596}, mesh = {Algorithms ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism ; Calibration ; Carcinoma, Ductal, Breast/*metabolism ; Diagnostic Imaging/methods ; Female ; Humans ; Image Processing, Computer-Assisted/*methods ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Software/*standards ; }, abstract = {BACKGROUND: The immunohistochemical detection of estrogen (ER) and progesterone (PR) receptors in breast cancer is routinely used for prognostic and predictive testing. Whole slide digitalization supported by dedicated software tools allows quantization of the image objects (e.g. cell membrane, nuclei) and an unbiased analysis of immunostaining results. Validation studies of image analysis applications for the detection of ER and PR in breast cancer specimens provided strong concordance between the pathologist's manual assessment of slides and scoring performed using different software applications.

METHODS: The effectiveness of two connected semi-automated image analysis software (NuclearQuant v. 1.13 application for Pannoramic™ Viewer v. 1.14) for determination of ER and PR status in formalin-fixed paraffin embedded breast cancer specimens immunostained with the automated Leica Bond Max system was studied. First the detection algorithm was calibrated to the scores provided an independent assessors (pathologist), using selected areas from 38 small digital slides (created from 16 cases) containing a mean number of 195 cells. Each cell was manually marked and scored according to the Allred-system combining frequency and intensity scores. The performance of the calibrated algorithm was tested on 16 cases (14 invasive ductal carcinoma, 2 invasive lobular carcinoma) against the pathologist's manual scoring of digital slides.

RESULTS: The detection was calibrated to 87 percent object detection agreement and almost perfect Total Score agreement (Cohen's kappa 0.859, quadratic weighted kappa 0.986) from slight or moderate agreement at the start of the study, using the un-calibrated algorithm. The performance of the application was tested against the pathologist's manual scoring of digital slides on 53 regions of interest of 16 ER and PR slides covering all positivity ranges, and the quadratic weighted kappa provided almost perfect agreement (κ = 0.981) among the two scoring schemes.

CONCLUSIONS: NuclearQuant v. 1.13 application for Pannoramic™ Viewer v. 1.14 software application proved to be a reliable image analysis tool for pathologists testing ER and PR status in breast cancer.}, } @article {pmid21243965, year = {2010}, author = {Boudry, M and Blancke, S and Braeckman, J}, title = {Irreducible incoherence and intelligent design: a look into the conceptual toolbox of a pseudoscience.}, journal = {The Quarterly review of biology}, volume = {85}, number = {4}, pages = {473-482}, doi = {10.1086/656904}, pmid = {21243965}, issn = {0033-5770}, mesh = {Animals ; *Biological Evolution ; Humans ; *Religious Philosophies ; }, abstract = {The concept of Irreducible Complexity (IC) has played a pivotal role in the resurgence of the creationist movement over the past two decades. Evolutionary biologists and philosophers have unambiguously rejected the purported demonstration of "intelligent design" in nature, but there have been several, apparently contradictory, lines of criticism. We argue that this is in fact due to Michael Behe's own incoherent definition and use of IC. This paper offers an analysis of several equivocations inherent in the concept of Irreducible Complexity and discusses the way in which advocates of the Intelligent Design Creationism (IDC) have conveniently turned IC into a moving target. An analysis of these rhetorical strategies helps us to understand why IC has gained such prominence in the IDC movement, and why, despite its complete lack of scientific merits, it has even convinced some knowledgeable persons of the impending demise of evolutionary theory.}, } @article {pmid21234642, year = {2011}, author = {de Azevedo, CR and Cruz, MR and Chinen, LT and Peres, SV and Peterlevitz, MA and de Azevedo Pereira, AE and Fanelli, MF and Gimenes, DL}, title = {Meningeal carcinomatosis in breast cancer: prognostic factors and outcome.}, journal = {Journal of neuro-oncology}, volume = {104}, number = {2}, pages = {565-572}, pmid = {21234642}, issn = {1573-7373}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Meningeal Carcinomatosis/mortality/*secondary/therapy ; Middle Aged ; Neoplasm Staging ; Prognosis ; Radiotherapy ; Treatment Outcome ; }, abstract = {Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.}, } @article {pmid21234500, year = {2011}, author = {Ahr, B and Chollet, M and Adams, B and Lunny, EM and Laperle, CM and Rose-Petruck, C}, title = {Picosecond X-ray absorption measurements of the ligand substitution dynamics of Fe(CO)5 in ethanol.}, journal = {Physical chemistry chemical physics : PCCP}, volume = {13}, number = {13}, pages = {5590-5599}, doi = {10.1039/c0cp01856b}, pmid = {21234500}, issn = {1463-9084}, mesh = {Ethanol/*chemistry ; Iron Carbonyl Compounds/*chemistry ; Ligands ; X-Ray Absorption Spectroscopy ; }, abstract = {Ultrafast X-ray absorption near edge spectroscopy has been carried out for photo excited iron pentacarbonyl in ethanol with 2 picosecond resolution. A temporal resolution limited dissociation process was observed, followed by the formation of the mono-substituted complex Fe(CO)(4)EtOH within a few tens of picoseconds. The measurements have been carried out with a newly developed X-ray absorption instrument at station 7 ID-C of the Advanced Photon Source. The results show that single picosecond temporal resolution can be achieved at a synchrotron beam line.}, } @article {pmid21228925, year = {2010}, author = {Lacroix-Triki, M and Lambros, MB and Geyer, FC and Suarez, PH and Reis-Filho, JS and Weigelt, B}, title = {Absence of microsatellite instability in mucinous carcinomas of the breast.}, journal = {International journal of clinical and experimental pathology}, volume = {4}, number = {1}, pages = {22-31}, pmid = {21228925}, issn = {1936-2625}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Adenocarcinoma, Mucinous/*genetics/pathology ; Adenosine Triphosphatases/metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; DNA Repair Enzymes/metabolism ; DNA, Neoplasm ; DNA-Binding Proteins/metabolism ; Female ; Humans ; Immunohistochemistry ; Microdissection ; *Microsatellite Instability ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/metabolism ; Neoplasm Staging ; Nuclear Proteins/metabolism ; Tissue Array Analysis ; }, abstract = {Microsatellite instability (MSI) is a form of genetic instability that results from defects in DNA mismatch repair. MSI is reported to be rare in unselected breast cancers, however it is a common feature in subsets of colorectal, ovarian and endometrial cancers. In these anatomical sites, MSI-high carcinomas often display a mucinous histology. The aim of this study was to determine whether mucinous carcinomas of the breast would more frequently display MSI-high than invasive ductal carcinomas of no special type (IDC-NSTs). The expression of four MSI markers (i.e. MSH2, MSH6, MLH1 and PMS2) was immunohistochemically assessed in 35 mucinous breast carcinomas and 35 histological grade- and oestrogen receptor (ER) status-matched IDC-NSTs, and in a series of 245 invasive breast cancers. Cases were considered as potentially MSI-high if tumour cells lacked expression of at least two MSI markers and internal controls displayed nuclear staining. Nine mucinous carcinomas were microdissected and subjected to MSI analysis by PCR using the MSI markers BAT26 and BAT40. No immunohistochemical evidence of MSI-high was found in the 35 mucinous carcinomas and 35 grade- and ER-matched IDC-NSTs, and in the cohort of 245 invasive breast cancers. In addition, no evidence of MSI-high was observed by PCR analysis using the BAT26 and BAT40 markers in the nine mucinous carcinomas tested. Our results demonstrate that MSI-high phenotype is remarkably rare in invasive breast cancer, and that, in contrast to mucinous carcinomas of other anatomical sites, MSI is not a common event in mucinous carcinomas of the breast.}, } @article {pmid21224709, year = {2010}, author = {Kashiwagi, S and Kawajiri, H and Noda, S and Takashima, T and Onoda, N and Nakata, B and Kato, Y and Ishikawa, T and Hirakawa, K}, title = {[A case of multicentric breast cancer in which an effect of neoadjuvant chemotherapy had a disparity].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {12}, pages = {2775-2777}, pmid = {21224709}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Carcinoma, Lobular/*drug therapy/*pathology ; Cyclophosphamide/therapeutic use ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasms, Multiple Primary/*drug therapy/*pathology ; }, abstract = {A 61-year-old woman was visited our hospital for a left breast tumor. Ultrasonography (US) demonstrated two tumors comprising a tumor 3.3 cm in diameter in the A area and another one 0.9 cm in diameter in the C area of the left breast, and US-guided core needle biopsy (CNB) was performed. The histological findings showed invasive ductal carcinoma, ER (+)/PR (-)/HER2 (+) in the A lesion and ER (+)/PR (+)/HER2 (-) in the C lesion. At this point in time, US demonstrated a new tumor 1.9 cm in diameter in the outside C area of the left breast, and CNB was performed. The histological findings showed invasive ductal carcinoma, ER (+)/PR (+)/HER2 (-) in the outside C lesion. Chemotherapy was estimated as PD, and an operation was performed (Bt + Ax). Histopathological examination showed pCR in the A lesion, invasive lobular carcinoma in the C lesion and solid-tubular carcinoma in the outside C new lesion. Depend on each subtype, HER2/new targeting trastuzumab therapy, radiation therapy and ER/PR targeting hormone therapy were tried as a post operative treatment.}, } @article {pmid21224704, year = {2010}, author = {Katsuta, E and Ohkubo, T and Someno, Y and Saguchi, M and Aoyagi, H and Takahata, T and Hasegawa, K and Hamada, S and Kaneko, J and Maejima, S}, title = {[A long-term survival case of local recurrence of breast cancer treated with combined modality therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {12}, pages = {2760-2762}, pmid = {21224704}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Hormonal/administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Neoplasm Recurrence, Local ; Paclitaxel/administration & dosage ; Tamoxifen/administration & dosage ; Taxoids/administration & dosage ; Tegafur/administration & dosage ; Trastuzumab ; Uracil/administration & dosage ; }, abstract = {The case was a 70-year-old woman. In 1997, the patient underwent pectoral muscle-preserving mastectomy and axillary/subclavicular lymph node dissection for the treatment of right breast cancer. Histological diagnosis was invasive ductal carcinoma (T2, N2, M0, Stage IIIA). She received a combination therapy with TAM and UFT for 5 years postoperatively. Because tumor recurrence occurred in right axillary lymph nodes in the 9th postoperative year, the patient underwent resection of these lymph nodes followed by 6 cycles of AC-based chemotherapy. Multiple lung metastases occurred in the 10th postoperative year, and then, the patient received 8 cycles of DOC-based chemotherapy. In the 11th postoperative year, a mass appeared again in the right axilla, and 6 cycles of capecitabine-based chemotherapy was administered. In the 12th postoperative year, pulmonary metastasis was in progression and an increased right axillary mass were noted. Thus, the specimen extirpated in 2006 was examined again, revealing negative ER, negative PgR and positive HER2. Six cycles of combined trastuzumab+PTX therapy were administered. Lung metastasis decreased in size, allowing a judgment of partial response. Because the right axillary mass had grown to 10 cm, and the patient's QOL was reduced, it was extirpated. The patient is scheduled to receive a postoperative radiotherapy, followed by resumption of chemotherapy.}, } @article {pmid21224702, year = {2010}, author = {Oda, G and Nakagawa, T and Sato, T and Kuwayama, T and Yamamoto, K and Kawachi, H and Kubota, K and Sugihara, K}, title = {[A case of stage IV breast cancer with bone metastases that responded well for long-term to hormonal therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {12}, pages = {2753-2755}, pmid = {21224702}, issn = {0385-0684}, mesh = {Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Bone Neoplasms/drug therapy/*secondary ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Diphosphonates/therapeutic use ; Female ; Gonadotropin-Releasing Hormone/*therapeutic use ; Humans ; Middle Aged ; Nitriles/*therapeutic use ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tamoxifen/*therapeutic use ; Triazoles/*therapeutic use ; }, abstract = {A case was a 48 years old woman. She was aware of a lump in her left breast and visited our hospital. We diagnosed it as an invasive ductal carcinoma. Immunostaining for both ER and PgR was strongly positive. CT of the initial consultation showed multiple bone metastases (thoracic vertebrae, lumbar vertebrae, and iliac bone). After AC followed by docetaxel and tamoxifen, LH-RH analogue was started. We used anastrozole after menopause. The bisphosphonate has been used from the beginning of the treatment. After the chemotherapy, the clinical response of primary tumor was judged as partial response. For six years, the size of primary tumor has not been changed, and PET-CT has not showed another metastasis. Anastrozole was superior to tamoxifen with respect to TTP (median values of 10.7 and 6.4 months for anastrozole and tamoxifen, respectively) in postmenopausal women with ER and/or PgR receptor positive tumors. Our study indicated that many patients responding to hormonal therapy appear to have been increasing from now on.}, } @article {pmid21224074, year = {2011}, author = {Kim, BG and An, HJ and Kang, S and Choi, YP and Gao, MQ and Park, H and Cho, NH}, title = {Laminin-332-rich tumor microenvironment for tumor invasion in the interface zone of breast cancer.}, journal = {The American journal of pathology}, volume = {178}, number = {1}, pages = {373-381}, pmid = {21224074}, issn = {1525-2191}, mesh = {Breast Neoplasms/*genetics/*pathology ; Cadherins/genetics ; Cell Adhesion Molecules/*genetics ; Epithelial Cells/metabolism/pathology ; Epithelial-Mesenchymal Transition/genetics ; Female ; *Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics ; Humans ; Integrin alpha6beta4/genetics ; Matrix Metalloproteinase 14/genetics ; MicroRNAs/genetics ; Myofibroblasts/metabolism/pathology ; Neoplasm Invasiveness ; Snail Family Transcription Factors ; Transcription Factors/genetics ; *Tumor Microenvironment ; Zinc Finger E-box-Binding Homeobox 1 ; }, abstract = {Dense fibrosis, which is caused by desmoplastic reaction, is usually found in invasive ductal carcinoma and may represent the alteration of the tumor microenvironment preceding tumor invasion. Thus, the dense fibrotic zone around invasive ductal carcinoma can be considered to be the actual tissue site of tumor microenvironment, where the precedent alterations for tumor invasion occur. To characterize the dense fibrotic zone, we classified invasive ductal carcinoma tissue into a tumor zone, a normal zone, and the novel interface zone (IZ), which shows dense fibrosis. The postulated IZ is a 5-mm-wide belt that circles the tumor margin and overlaps with normal tissue. Of the extracellular matrix components, laminin-332 was specifically overexpressed in the IZ. Events that appear to be similar to the epithelial-mesenchymal transition, a novel source of myofibroblast formation from epithelial cells, were observed in the IZ, according to the following characteristics: overexpression of matrix metalloproteinase 3, membrane type 1-matrix metalloproteinase, snail, and zinc finger E-box-binding homeobox 1, and the gain of N-cadherin expression, as well as the down-regulation of miR200c. The myofibroblasts isolated from the IZ, which were designated interface zone-fibroblast, displayed laminin-332 and membrane type 1-matrix metalloproteinase overexpression, in contrast with both cancer-associated fibroblasts and normal breast fibroblasts. Taken together, our results suggest that the IZ, which shows dense fibrosis, may provide a specialized microenvironment for guiding tumor invasion: the fibrosis caused by laminin-332 overexpressing myofibroblast formation (interface zone-fibroblast) via epithelial-mesenchymal transition.}, } @article {pmid21221635, year = {2011}, author = {Kuba, S and Ohtani, H and Yamaguchi, J and Hayashi, H and Uga, T and Kanematsu, T and Shimokawa, I}, title = {Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {458}, number = {2}, pages = {159-169}, pmid = {21221635}, issn = {1432-2307}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Carcinoma, Papillary/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/biosynthesis ; Prognosis ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.}, } @article {pmid21221174, year = {2010}, author = {Lloyd, MC and Allam-Nandyala, P and Purohit, CN and Burke, N and Coppola, D and Bui, MM}, title = {Using image analysis as a tool for assessment of prognostic and predictive biomarkers for breast cancer: How reliable is it?.}, journal = {Journal of pathology informatics}, volume = {1}, number = {}, pages = {29}, pmid = {21221174}, issn = {2153-3539}, abstract = {BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) are important and well-established prognostic and predictive biomarkers for breast cancers and routinely tested on patient's tumor samples by immunohistochemical (IHC) study. The accuracy of these test results has substantial impact on patient management. A critical factor that contributes to the result is the interpretation (scoring) of IHC. This study investigates how computerized image analysis can play a role in a reliable scoring, and identifies potential pitfalls with common methods.

MATERIALS AND METHODS: Whole slide images of 33 invasive ductal carcinoma (IDC) (10 ER and 23 HER2) were scored by pathologist under the light microscope and confirmed by another pathologist. The HER2 results were additionally confirmed by fluorescence in situ hybridization (FISH). The scoring criteria were adherent to the guidelines recommended by the American Society of Clinical Oncology/College of American Pathologists. Whole slide stains were then scored by commercially available image analysis algorithms from Definiens (Munich, Germany) and Aperio Technologies (Vista, CA, USA). Each algorithm was modified specifically for each marker and tissue. The results were compared with the semi-quantitative manual scoring, which was considered the gold standard in this study.

RESULTS: For HER2 positive group, each algorithm scored 23/23 cases within the range established by the pathologist. For ER, both algorithms scored 10/10 cases within range. The performance of each algorithm varies somewhat from the percentage of staining as compared to the pathologist's reading.

CONCLUSIONS: Commercially available computerized image analysis can be useful in the evaluation of ER and HER2 IHC results. In order to achieve accurate results either manual pathologist region selection is necessary, or an automated region selection tool must be employed. Specificity can also be gained when strict quality assurance by a pathologist is invested. Quality assurance of image analysis by pathologists is always warranted. Automated image analysis should only be used as adjunct to pathologist's evaluation.}, } @article {pmid21218740, year = {2010}, author = {Alwan, NA}, title = {Breast cancer: demographic characteristics and clinico-pathological presentation of patients in Iraq.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {16}, number = {11}, pages = {1159-1164}, pmid = {21218740}, issn = {1020-3397}, mesh = {Adult ; Age Distribution ; Aged ; Aneuploidy ; *Breast Neoplasms/epidemiology/etiology/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/analysis/genetics ; Female ; Genes, erbB-2/genetics ; Humans ; Immunohistochemistry ; Iraq/epidemiology ; Middle Aged ; Neoplasm Staging ; Population Surveillance ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Residence Characteristics ; Risk Factors ; }, abstract = {Breast cancer is the commonest type of malignancy in Iraq. The study was carried out on 721 out of a total of 5044 patients (14.3%) presenting with palpable breast lumps that were diagnosed as cancer. Approximately one third of the breast cancer patients were diagnosed at age 40-49 years; 71.9% came from urban areas; and 75% were married. History of lactation was reported in 63.1% and hormonal therapy in 29%. Positive family history was recorded in 16.2%. Although the lump was detected by the patient herself in 90.6% of cases, only 32% sought medical advice within the first month. Accordingly, 47% of these patients presented in advanced stages (III and IV). The main histological type was invasive ductal carcinoma, in which pathological changes of grade II and III were observed in 56.6% and 39.9% respectively. DNA analysis showed that 80.3% of the carcinomas were aneuploid. The findings of this study justify increasing efforts for establishing comprehensive breast cancer control programmes in Iraq.}, } @article {pmid21215164, year = {2010}, author = {Chen, J and Zhang, X and Tian, R and Liu, Y and Dong, HM and Guo, RF and Liang, HY}, title = {[Expression of androgen receptor in breast carcinoma and its relationship with estrogen receptor, progesterone receptor and HER2 status].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {39}, number = {11}, pages = {743-746}, pmid = {21215164}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/*metabolism ; Receptors, Androgen/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {OBJECTIVE: to investigate the expression of androgen receptor (AR) in breast carcinoma and its relationship with estrogen receptor (ER), progesterone receptor (PR) and HER2 status, and to discuss its potential as treatment target.

METHODS: immunohistochemical method was used to detect AR, ER, PR and HER2 expression in 175 cases of invasive ductal carcinoma of breast, which were divided into four groups: luminal A, luminal B, HER2(-) overexpression and triple negative group.

RESULTS: eighty-eight cases (50.3%) were AR positive in 175 cases, the expression of AR was positively correlated with ER, PR and HER2 status. All the cases were grouped as follows: 53 cases (30.3%) were luminal A, 33 cases (18.9%) were luminal B, 23 cases (13.1%) were HER2(-) overexpression and 66 cases (37.7%) were triple negative, the AR expression rate was 56.6% (30/53), 75.8% (25/33), 47.8% (11/23), 33.3% (22/66), respectively. There was significant difference among the four groups' AR expression rates. With respect to the clinico-pathological features, AR positive cases were younger in luminal A and had lower mitosis rate in triple negative subgroups than the negative cases (χ(2) = 4.567, P = 0.033; χ(2) = 5.140, P = 0.023, respectively).

CONCLUSION: AR has a high positive rate in breast carcinoma, and may be an ideal therapeutic target for breast carcinoma, especially for the triple negative subtype.}, } @article {pmid21214522, year = {2011}, author = {Jin, B and Ni, H and Geshang, Q and Li, Y and Shen, W and Shi, H}, title = {HLA-DR4 antigen and idiopathic dilated cardiomyopathy susceptibility: a meta-analysis involving 11,761 subjects.}, journal = {Tissue antigens}, volume = {77}, number = {2}, pages = {107-111}, doi = {10.1111/j.1399-0039.2010.01589.x}, pmid = {21214522}, issn = {1399-0039}, mesh = {Cardiomyopathy, Dilated/*genetics/immunology ; Case-Control Studies ; *Genetic Predisposition to Disease ; HLA-DR4 Antigen/*genetics/immunology ; Histocompatibility Testing ; Humans ; Risk Factors ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR4 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies in English-language articles were identified by a search of PubMed and Embase database (inception to June 2010). A total of 19 case-control studies including 1378 cases and 10,383 controls provided data on the association between HLA-DR4 antigen and genetic susceptibility to IDC. Overall, statistically elevated frequency of HLA-DR4 allele [OR (odds ratio), 1.58; 95% CI (confidence interval), 1.21-2.07; P = 0.0009] was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically increased risks were found for IDC in both subgroups. In the subgroup analysis by ethnicity, significantly increased risk was found among Europeans from 12 case-control studies (OR, 1.54; 95% CI, 1.11-2.12; P = 0.009). In conclusion, our results suggest that HLA-DR4 antigen is a low-penetrant risk factor for developing IDC in Europeans.}, } @article {pmid21213079, year = {2014}, author = {Tang, X and Umemura, S and Kumaki, N and Izumi, M and Saito, Y and Suzuki, Y and Ozawa, A and Tokuda, Y}, title = {A case report of pigmented mammary Paget's disease mimicking nevus of the nipple.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {3}, pages = {370-374}, doi = {10.1007/s12282-010-0249-y}, pmid = {21213079}, issn = {1880-4233}, mesh = {Adult ; Breast Neoplasms/*pathology ; Female ; Humans ; Nevus/*pathology ; Nipples/*pathology ; Paget's Disease, Mammary/*pathology ; Skin Neoplasms/*pathology ; }, abstract = {A 43-year-old Japanese woman consulted our hospital for a pigmented lesion on her right nipple. Two years later, the lesion became enlarged, measuring 5 × 5 mm. It was dark brown, had an irregular shape and relatively clear borders. Incisional biopsy yielded a pathological diagnosis of junctional nevus of the skin. An additional 2 years later, a small mass developed under the right nipple area and core needle biopsy yielded a pathologic diagnosis of invasive ductal carcinoma. Partial resection of the right EC areas included the skin of the nipple and sentinel lymph node biopsy was performed. Histologically, the skin of the nipple demonstrated small clusters of pigmented carcinoma cells that were low molecular weight cytokeratin (CAM5.2) positive. Most of the carcinoma cells were small and did not have abundant cytoplasm, but nuclear enlargement and prominent nucleoli indicated malignancy, and the cytoplasm was pale compared with that of the surrounding squamous epithelial cells. Scattered dendritic melanocytes were identified by S-100 protein and HMB-45 immunohistochemically. In the upper dermis, carcinoma cells also involved the lactiferous ducts. A small focus of carcinoma cells that invaded the fat tissues did not contain melanin pigment. The final diagnosis was pigmented mammary Paget's disease. Pigmented lesions on the nipple should be carefully examined, because pigmented mammary Paget's disease sometimes mimics malignant melanoma or junctional nevus.}, } @article {pmid21212063, year = {2011}, author = {Huang, Y and Malone, KE and Cushing-Haugen, KL and Daling, JR and Li, CI}, title = {Relationship between menopausal symptoms and risk of postmenopausal breast cancer.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {20}, number = {2}, pages = {379-388}, pmid = {21212063}, issn = {1538-7755}, support = {R01 CA085913-05/CA/NCI NIH HHS/United States ; R01-CA8591/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Body Composition ; Body Mass Index ; Breast Neoplasms/drug therapy/*epidemiology ; Carcinoma, Ductal, Breast/drug therapy/*epidemiology ; Carcinoma, Lobular/drug therapy/*epidemiology ; Case-Control Studies ; Cohort Studies ; Female ; Follow-Up Studies ; Hot Flashes ; Humans ; *Menopause ; Middle Aged ; *Postmenopause ; Prognosis ; Risk Factors ; Survival Rate ; United States/epidemiology ; }, abstract = {BACKGROUND: Prior studies indicate that women with menopausal symptoms have lower estrogen levels because they go through menopause as compared with women who do not experience them. Given the central role of hormones in the etiology of breast cancer, a link between menopausal symptoms and breast cancer is plausible. However, no prior studies have evaluated the association between menopausal symptoms and breast cancer risk.

METHODS: Utilizing data from a population-based case-control study we examined associations between menopausal symptoms and risks of different histologic types of breast cancer among postmenopausal women. We calculated multivariate adjusted odds ratios (OR) using polytomous logistic regression and evaluated several potential effect modifiers.

RESULTS: Women who ever experienced menopausal symptoms had lower risks of invasive ductal carcinoma [(IDC) OR = 0.5; 95% CI: 0.3-0.7], invasive lobular carcinoma (ILC, OR = 0.5; 95% CI: 0.3-0.8), and invasive ductal-lobular carcinoma (IDLC, OR = 0.7; 95% CI: 0.4-1.2), and these reductions in risk were independent of recency and timing of hormone therapy use, age at menopause, and body mass index. Increasing intensity of hot flushes among women who ever experienced hot flushes was also associated with decreasing risks of all three breast cancer subtypes (P values for trend all ≤ 0.017).

CONCLUSION: This is the first study to report that women who ever experienced menopausal symptoms have a substantially reduced risk of breast cancer, and that severity of hot flushes is also inversely associated with risk.

IMPACT: If confirmed, these findings could enhance our understanding of breast cancer etiology and factors potentially relevant to prevention.}, } @article {pmid21207256, year = {2011}, author = {Kadivar, M and Monabati, A and Joulaee, A and Hosseini, N}, title = {Epstein-Barr virus and breast cancer: lack of evidence for an association in Iranian women.}, journal = {Pathology oncology research : POR}, volume = {17}, number = {3}, pages = {489-492}, pmid = {21207256}, issn = {1532-2807}, mesh = {Adolescent ; Adult ; Breast/metabolism/pathology ; Breast Neoplasms/*diagnosis/genetics/virology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/virology ; Carcinoma, Lobular/*diagnosis/genetics/virology ; DNA, Viral/genetics ; Epstein-Barr Virus Infections/*diagnosis/genetics/virology ; Epstein-Barr Virus Nuclear Antigens/*genetics/metabolism ; Female ; Herpesvirus 4, Human/genetics ; Humans ; Immunoenzyme Techniques ; Iran ; Middle Aged ; Polymerase Chain Reaction ; Viral Matrix Proteins/*genetics/metabolism ; Viral Proteins/*genetics/metabolism ; Young Adult ; }, abstract = {Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.}, } @article {pmid21206008, year = {2010}, author = {Liang, S and Singh, M and Dharmaraj, S and Gam, LH}, title = {The PCA and LDA analysis on the differential expression of proteins in breast cancer.}, journal = {Disease markers}, volume = {29}, number = {5}, pages = {231-242}, doi = {10.3233/DMA-2010-0753}, pmid = {21206008}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Humans ; Linear Models ; Malaysia ; Middle Aged ; Principal Component Analysis ; Protein Biosynthesis ; Proteome/metabolism ; }, abstract = {Breast cancer is a leading cause of mortality in women. In Malaysia, it is the most common cancer to affect women. The most common form of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was undertaken to identify protein profile changes between cancerous and normal breast tissues from 18 patients. Two protein extracts; aqueous soluble and membrane associated protein extracts were studied. Thirty four differentially expressed proteins were identified. The intensities of the proteins were used as variables in PCA and reduced data of six principal components (PC) were subjected to LDA in order to evaluate the potential of these proteins as collective biomarkers for breast cancer. The protein intensities of SEC13-like 1 (isoform b) and calreticulin contributed the most to the first PC while the protein intensities of fibrinogen beta chain precursor and ATP synthase D chain contributed the most to the second PC. Transthyretin precursor and apolipoprotein A-1 precursor contributed the most to the third PC. The results of LDA indicated good classification of samples into normal and cancerous types when the first 6 PCs were used as the variables. The percentage of correct classification was 91.7% for the originally grouped tissue samples and 88.9% for cross-validated samples.}, } @article {pmid21199632, year = {2010}, author = {Breton, AL and Poulalhon, N and Balme, B and Thomas, L and Dalle, S}, title = {Primary cutaneous marginal zone lymphoma as a complication of radiation therapy: Case report and review.}, journal = {Dermatology online journal}, volume = {16}, number = {12}, pages = {6}, pmid = {21199632}, issn = {1087-2108}, mesh = {Aged ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/radiotherapy/surgery ; Chlorambucil/administration & dosage ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone/drug therapy/*etiology ; Neoplasms, Radiation-Induced/drug therapy/*etiology ; Neoplasms, Second Primary/drug therapy/*etiology ; Radiotherapy, Adjuvant/*adverse effects ; Rituximab ; Skin Neoplasms/drug therapy/*etiology ; }, abstract = {BACKGROUND: The occurrence of primary cutaneous B-cell lymphoma at the site of radiation therapy is exceptional. We report herein the case of a primary cutaneous marginal zone lymphoma arising at the site of radiotherapy for breast cancer.

METHODS/RESULTS: A seventy-year-old woman was diagnosed in 2005 with an invasive ductal carcinoma of the left breast, which was treated with surgery, adjuvant chemotherapy, and radiation therapy. Three years later she developed several cutaneous nodules on her left breast, followed by similar lesions on her back. Histologic, immunohistochemistry, and molecular findings were consistent with the diagnosis of cutaneous marginal zone lymphoma. Physical examination was otherwise negative, as well as mammography, total body CT, bone marrow biopsy, and Borrelia serology.

CONCLUSIONS: To our knowledge, this is the first published case of primary cutaneous marginal zone lymphoma occurring at the site of radiotherapy. Cutaneous surveillance is proposed from the first year after irradiation in order to detect new primary malignancies, including this rare cutaneous neoplasm.}, } @article {pmid21197096, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to stage and grade of patients.}, journal = {Journal of biomedicine & biotechnology}, volume = {2010}, number = {}, pages = {516469}, pmid = {21197096}, issn = {1110-7251}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis ; Breast/metabolism ; Breast Neoplasms/*metabolism ; Cohort Studies ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Immunoblotting ; Malaysia ; Mass Spectrometry ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Protein Biosynthesis ; Proteomics/*methods ; }, abstract = {Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer. A proteomic approach was used to identify changes in the protein profile of breast cancerous and normal tissues. The patients were divided into different cohorts according to tumour stage and grade. We identified twenty-four differentially expressed hydrophilic proteins. A few proteins were found significantly related to various stages and grades of IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein zeta, and 14-3-3 protein eta. In this study, we found that by defining the expression of the proteins according to stages and grades of IDC, a significant relationship between the expression of the proteins with the stage or grade of IDC can be established, which increases the usefulness of these proteins as biomarkers for IDC.}, } @article {pmid21194459, year = {2010}, author = {Tambasco, M and Eliasziw, M and Magliocco, AM}, title = {Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival.}, journal = {Journal of translational medicine}, volume = {8}, number = {}, pages = {140}, pmid = {21194459}, issn = {1479-5876}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Epithelium/*pathology ; Female ; Fractals ; Humans ; Kaplan-Meier Estimate ; Keratins/metabolism ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Proportional Hazards Models ; Reproducibility of Results ; Tissue Array Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade). There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity) for invasive ductal carcinoma of the breast.

METHODS: We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA) cores derived from 379 patients. Patients were categorized according to low (<1.56, N = 141), intermediate (1.56-1.75, N = 148), and high (>1.75, N = 90) fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status.

RESULTS: Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p < 0.001). Overall 10-year survival showed a similar association. Fractal dimension, nodal status, and grade were the only significant (P < 0.05) independent predictors for both disease-specific and overall survival. Among all of the prognosticators, the fractal dimension hazard ratio for disease-specific survival, 2.6 (95% confidence interval (CI) = 1.4,4.8; P = 0.002), was second only to the slightly higher hazard ratio of 3.1 (95% CI = 1.9,5.1; P < 0.001) for nodal status. As for overall survival, fractal dimension had the highest hazard ratio, 2.7 (95% CI = 1.6,4.7); P < 0.001). Split-sample cross-validation analysis suggests these results are generalizable.

CONCLUSION: Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.}, } @article {pmid24212806, year = {2011}, author = {Hasumi, K and Aoki, Y and Watanabe, R and Hankey, KG and Mann, DL}, title = {Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell based immunotherapy and intensity-modulated radiotherapy.}, journal = {Cancers}, volume = {3}, number = {2}, pages = {2223-2242}, pmid = {24212806}, issn = {2072-6694}, abstract = {Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.}, } @article {pmid23776766, year = {2011}, author = {Singhai, R and Patil, V and Patil, A}, title = {Status of HER-2/neu receptors and Ki-67 in breast cancer of Indian women.}, journal = {International journal of applied & basic medical research}, volume = {1}, number = {1}, pages = {15-19}, pmid = {23776766}, issn = {2229-516X}, abstract = {BACKGROUND: Breast cancer is a leading cause of death in women. Receptor status is the most important prognostic and predictive marker for breast cancer.

AIMS: The present study was conducted with an aim to analyze breast cancer of Indian women with discordant receptor status, probably hormone dependent estrogen receptor (ER) positive, progesterone receptor (PgR) negative or ER- negative and PgR+ positive subgroup profile, infiltrating ductal breast cancer (IDC) not otherwise specified.

MATERIALS AND METHODS: Specimens from 100 IDC were grouped into three categories according to hormonal status (group 1: ER+ positive and PgR+ positive, group 2: ER+ positive and PgR- negative or ER- negative and PgR+ positive, group 3: ER- negative and PgR- negative) evaluated prognostic parameters.

STATISTICAL ANALYSIS: Statistically significant difference was found between tumor receptor status distribution and menopausal status (P = 0.0235), age of patients (P < 0.001), histopathologic grade (P < 0.001), vascular invasion (P = 0.006), HER-2/neu status (P = 0.004) and Ki-67 proliferation rate (P < 0.001).

RESULTS: Group 1 tumors were found exclusively in post-menopausal patients with average age 68.9 years, most of which had intermediate grade II, without vascular invasion, with HER-2/neu status score predominantly 0 or 1+ and lower Ki-67 proliferation rate. Group 2 tumors were found predominantly in younger post-menopausal patients with average age 57.5 years, with vascular invasion found in 23% of cases. Group 3 tumors mostly had higher histopathologic grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases.

CONCLUSION: It is concluded that patients with group 2 breast cancer were younger post-menopausal women, with tumors moderately differentiated, HER-2/neu score 0 or 1+ and with lower Ki-67 proliferation rate.}, } @article {pmid22830133, year = {2011}, author = {Tasneem, S and Khan, MM and Khawaja, MY}, title = {Demographic pattern of male breast cancer: an institutional based study.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {23}, number = {1}, pages = {3-4}, pmid = {22830133}, issn = {1025-9589}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*epidemiology/pathology ; Carcinoma, Ductal, Breast/epidemiology ; Carcinoma, Papillary/epidemiology ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Staging ; Pakistan/epidemiology ; }, abstract = {BACKGROUND: Male breast cancer incidence rises with age with peak in the 6th & 7th decade. It is one of the rare diseases and accounts for less than 1% of all malignancies worldwide. It is usually diagnosed in the late stage with poor prognosis.

OBJECTIVE: The purpose of this study was to know the demographic pattern and tumour characteristic of breast cancer in men reported at Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar.

METHODS: Retrospective data was collected from the (IRNUM), Peshawar for a period of three years (2006-2008). The evaluation was done from the histopathological reports of mastectomy and biopsy specimens. All male patients in the age group 26-86 year with breast cancer were included in the study. The age of the patients and tumour characteristics recorded were size, grade, type, skin involvement and stage.

RESULTS: Total number of male patients with breast cancer were 31 (2.1%) out of the total patients with breast malignancy during the study period with the mean age of 58.3 years. Tumour size ranged from 2 to 12 Cm. with average of 3.6 Cm. Invasive ductal carcinoma was found in 87%, papillary carcinoma in 6.5%, each of malignant fibrous histocytoma and sarcoma in 3.2% cases. Maximum number of patients was of grade II (41%).Patients in whom stage of the disease was known were 22 cases with 45.5% had stage III disease and 32% had stage IV disease. Skin involvement was found positive in 8 (25.8%).

CONCLUSION: Due to poor health care system breast cancer is diagnosed in a late stage of the disease and prognosis is poor.}, } @article {pmid22689722, year = {2011}, author = {Ahmed, M and Basit, A}, title = {Isolated adenocarcinoma of the nipple.}, journal = {BMJ case reports}, volume = {2011}, number = {}, pages = {}, pmid = {22689722}, issn = {1757-790X}, mesh = {Adenocarcinoma/*diagnosis/pathology/surgery ; Biopsy ; Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Nipples/*pathology ; Ultrasonography, Mammary ; }, abstract = {A 47-year-old female presented with a 1-year history of 'eczematous change' to the right nipple. Bilateral mammography and ultrasound were entirely normal. Free hand biopsy demonstrated invasive adenocarcinoma of the nipple. The patient underwent a right-sided central segmentectomy and sentinel node biopsy. Histology demonstrated that the nipple was almost completely replaced by an invasive ductal carcinoma with a maximum diameter of 13 mm. Invasion of the underlying breast tissue was to a depth of 3 mm. A single sentinel lymph node demonstrated metastatic carcinoma. Her oestrogen receptor status was positive while HER-2 status was negative. The patient subsequently underwent right-sided axillary node clearance to level three nodes. All 17 nodes in the specimen were found to be within normal limits. She is scheduled to undergo radiotherapy, chemotherapy and hormonal treatment.}, } @article {pmid22531122, year = {2011}, author = {Mizushima, Y and Yamaguchi, R and Yokoyama, T and Ogo, E and Nakashima, O}, title = {Recurrence of invasive micropapillary carcinoma of the breast with different ultrasound features according to lesion site: case report.}, journal = {The Kurume medical journal}, volume = {58}, number = {3}, pages = {81-85}, doi = {10.2739/kurumemedj.58.81}, pmid = {22531122}, issn = {1881-2090}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Papillary/*diagnostic imaging/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/diagnostic imaging/pathology ; Recurrence ; Ultrasonography, Mammary ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a distinct variant of breast cancer. Extensive lymphatic penetration, lymph node metastasis, and local recurrence are seen at a relatively high frequency. On ultrasound (US) findings, IMPC has been reported to be an irregular or lobulated mass with hypoechoic internal areas, but as yet there is no consensus regarding typical findings. A 52-year-old female noticed a mass less than 3 cm in diameter in her left upper breast. US findings indicated an irregularly shaped, hypoechoic tumor with indistinct margins. The diagnosis according to fine-needle aspiration cytology was invasive ductal carcinoma. She underwent lymph node dissection with mastectomy of the left breast. Histological examination revealed mixed-type IMPC. Three years and three months after surgery, IMPC recurred under the skin of the surgical scar. US findings indicated a hyperechoic tumor in this region. Eight months after further surgery, a tumor in the anterior chest wall was observed. US findings indicated an oval hypoechoic tumor with posterior acoustic enhancement. US findings differed between primary and recurrent IMPC because of differences in the occupancy and distribution of IMPC. We describe here a comparison between US and histological findings, as well as differences in IMPC between primary, secondary and tertiary sites.}, } @article {pmid22470813, year = {2011}, author = {Yarmohammadi, H and Nakamoto, D and Faulhaber, PF and Miedler, J and Azar, N}, title = {Inflammatory pseudotumor of the spleen: review of clinical presentation and diagnostic methods.}, journal = {Journal of radiology case reports}, volume = {5}, number = {9}, pages = {16-22}, pmid = {22470813}, issn = {1943-0922}, mesh = {Aged, 80 and over ; Biopsy, Needle ; Female ; Granuloma, Plasma Cell/*diagnostic imaging/*pathology ; Humans ; Multimodal Imaging ; Positron-Emission Tomography ; Spleen/*diagnostic imaging/*pathology ; Splenic Diseases/*diagnosis ; Tomography, X-Ray Computed ; }, abstract = {We describe a 91-year-old woman with a clinical history of invasive ductal carcinoma of the breast diagnosed in 1991 who was admitted because of dizziness, poor appetite, and some swelling and tenderness over her cheeks. The patient's initial work up revealed a 5-cm well-demarcated hypodense solid lesion in her spleen with abnormally intense uptake on PET/CT scan raising suspicion for malignancy i.e. breast metastasis versus lymphoma. Further review demonstrated the presence of this splenic lesion, though slightly smaller, on a CT scan from ten years earlier (2000). An ultrasonographic guided core needle splenic biopsy was performed and the pathology result revealed histological findings compatible with inflammatory pseudotumor of the spleen. As a result, unnecessary splenectomy was avoided.}, } @article {pmid22393991, year = {2011}, author = {Moatter, T and Aban, M and Iqbal, W and Azam, I and Pervaiz, A and Siddiqui, F and Murad, F and Pervez, S}, title = {Status of HER2 amplification, polysomy 17 and histopathological features of 425 Pakistani breast cancer patients.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {12}, number = {11}, pages = {3069-3073}, pmid = {22393991}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/pharmacology/therapeutic use ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/*genetics/*pathology ; *Chromosome Duplication ; Chromosomes, Human, Pair 17/*genetics ; Female ; Gene Amplification/genetics ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Pakistan ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Trastuzumab ; }, abstract = {HER2 gene amplification in invasive breast cancer is a robust predictive marker for response to transtuzumab therapy. This study was undertaken to measure concordance between immunohistochemistry (IHC) and FISH for HER2 gene amplification in invasive breast tumors, as well as the presence of polysomy 17 and possible correlation with demographics and histopathological variables, including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and FISH methods. Association between IHC and FISH in both subsets was calculated by amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with 2+ expression showed amplification. In contrast, 39 (74%) demonstrated 3+ IHC score and HER2 gene amplification. The histological variables including tumor size, tumor type, and lymph node involvement did not influence the outcome of FISH analysis. The ER and PR status showed significantly greater positivity in patients negative for HER2 amplification. Polysomy 17 was detected in 23.7% patients and was positively associated with ER and PR expression (P= <0.05). Our study showed a concordance of 24% between 2+ IHC and FISH amplification, while in 3+ IHC cases the concordance was 74%. Significant links of HER2 amplification was seen with ER andPR negativity and higher tumor grade. In addition, non-significant correlations were noted with other variables like tumor type, size and lymph node status.}, } @article {pmid21191745, year = {2010}, author = {Tozaki, M and Fukuma, E}, title = {Accuracy of determining preoperative cancer extent measured by automated breast ultrasonography.}, journal = {Japanese journal of radiology}, volume = {28}, number = {10}, pages = {771-773}, pmid = {21191745}, issn = {1867-108X}, mesh = {Adult ; Aged ; Breast/surgery ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Carcinoma, Intraductal, Noninfiltrating/*diagnostic imaging/surgery ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; Middle Aged ; Preoperative Care/*methods ; Reproducibility of Results ; Retrospective Studies ; Ultrasonography, Mammary/*methods ; }, abstract = {PURPOSE: The aim of this study was to determine the accuracy of measuring preoperative cancer extent using automated breast ultrasonography (US).

MATERIALS AND METHODS: This retrospective study consisted of 40 patients with histopathologically confirmed breast cancer. All of the patients underwent automated breast US (ABVS; Siemens Medical Solutions, Mountain View, CA, USA) on the day before the surgery. The sizes of the lesions on US were measured on coronal multiplanar reconstruction images using the ABVS workstation. Histopathological measurement of tumor size included not only the invasive foci but also any in situ component and was used as the gold standard. The discrepancy of the tumor extent between automated breast US and the histological examination was calculated.

RESULTS: Automated breast US enabled visualization of the breast carcinomas in all patients. The mean size of the lesions on US was 12 mm (range 4-62 mm). The histopathological diagnosis was ductal carcinoma in situ (DCIS) in seven patients and invasive ductal carcinoma in 33 patients (18 without an intraductal component, 15 with an intraductal component). Lesions ranged in diameter from 4 to 65 mm (mean 16 mm). The accuracy of determination of the tumor extent with a deviation in length of <2 cm was 98% (39/40).

CONCLUSION: Automated breast US is thought to be useful for evaluating tumor extent preoperatively.}, } @article {pmid21188659, year = {2011}, author = {Pilkington Woll, JP and Cortés Romera, M and García Vicente, AM and González García, B and Delgado Portela, M and Cordero García, JM and Pardo García, R and Molino Trinidad, C and Soriano Castrejón, AM}, title = {Impact of radioguided occult lesion localization on the correct excision of malignant breast lesions: effect of histology and tumor size.}, journal = {Annals of nuclear medicine}, volume = {25}, number = {3}, pages = {197-203}, doi = {10.1007/s12149-010-0453-z}, pmid = {21188659}, issn = {1864-6433}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/*methods ; Breast Neoplasms/diagnostic imaging/*pathology/*surgery ; Humans ; Mammography ; Middle Aged ; Radionuclide Imaging ; Retrospective Studies ; Stereotaxic Techniques ; *Tumor Burden ; }, abstract = {AIM: To evaluate the impact of radioguided occult lesion localization (ROLL) in the correct location and excision of malignant breast lesions, and analyze if these results are affected by the histology and tumor size.

MATERIALS AND METHODS: A total of 105 patients with occult breast lesions were studied. The mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled macroaggregated human albumin (AMA) was administered using stereotaxic mammography or ultrasound. Surgical resection was carried out with the help of a gammadetector probe. In the histological study, disease-free margin was defined by a distance between the tumor lesion and the surgical margin of more than 1 mm. The possible influence of tumor histology and lesion diameter with respect to free/affected margins was analyzed.

RESULTS: Correct radiotracer placement was achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%), radiotracer placement was incorrect, with 2 of them being malignant lesions that were found by macroscopic inspection, and the other 3 having benign pathology. Among the malignant lesions (44 cases), correct placement of the radiotracer was achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL was correctly performed, free surgical margins were obtained in 24 cases (57.1%), while the other 18 (42.9%) had infiltrated surgical margins. The most common histological type among the malignant lesions was invasive ductal carcinoma (71.4%). The histological types with an increased frequency of infiltration of surgical margins were invasive and microinvasive cancer (94.4%). All the affected margins were in lesions greater than 10 mm, and the highest incidence was in those between 20 and 30 mm (55.5%).

CONCLUSION: In our experience, the advantages of the ROLL technique are a precise localization of malignant breast lesions (95.5%) and an increased probability of a complete excision with free margins in more than one half of them. Nevertheless, special consideration should be taken when dealing with invasive and microinvasive cancers and in those exceeding 10 mm because of their higher incidence of infiltrated margins.}, } @article {pmid21188047, year = {2010}, author = {Vijayakumar, EK and Gore, VG and Mahajan, A and Kumar, M}, title = {Isolation and characterization of a process impurity in tizanidine hydrochloride.}, journal = {Indian journal of pharmaceutical sciences}, volume = {72}, number = {3}, pages = {360-362}, pmid = {21188047}, issn = {1998-3743}, abstract = {A new process impurity was detected during the HPLC analysis of Tizanidine hydrochloride (I) batches. The impurity (II) was isolated by preparative HPLC and characterized by NMR and Mass spectral analysis as 5-S-ethyl-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine hydrochloride.}, } @article {pmid21187689, year = {2010}, author = {Tamura, T and Usui, S and Murakami, S and Arihiro, K and Akiyama, Y and Naito, K and Akiyama, M}, title = {Biexponential Signal Attenuation Analysis of Diffusion-weighted Imaging of Breast.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {9}, number = {4}, pages = {195-207}, doi = {10.2463/mrms.9.195}, pmid = {21187689}, issn = {1880-2206}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Diseases/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Fibroadenoma/*pathology ; Humans ; Middle Aged ; Papilloma, Intraductal/*pathology ; *Signal Processing, Computer-Assisted ; Young Adult ; }, abstract = {PURPOSE: in vivo, the attenuation of diffusion-weighted imaging (DWI) signal at high b-values is sometimes nonlinear when plotted with semilogarithmic function and is fit well by a biexponential function. Previous reports have indicated that the fast and slow component fractions of the apparent diffusion coefficient (ADC) can be derived by biexponential fitting and that these fractions correspond to the actual diffusion components in the extra- and intracellular space. In this study, we investigated the clinical utility of DWI for the breast by performing DWI using multiple b-factors on healthy volunteers and clinical subjects, analyzing the signal by fitting it with a biexponential equation, and comparing the fitting parameters of breast lesions.

PATIENTS AND METHODS: we investigated 8 healthy women as normal cases and 80 female patients with a total of 100 breast tumors (42 benign, 58 malignant tumors) as clinical cases. We performed DWI using 12 b-values for the healthy cases and 6 b-values for the clinical cases, up to a maximum b-value of 3500 s/mm(2).

RESULTS: decay of DWI signal of normal mammary glands, most cysts, and some fibroadenomas showed a monoexponential relationship, and conversely, that of intraductal papilloma (IDP) and malignant tumors was well fitted by a biexponential function. Comparison of parameters derived from biexponential fitting demonstrated no significant difference between benign and malignant lesions. For malignant tumor subtype, the fast component fraction of noninvasive ductal carcinoma was statistically greater than that of invasive ductal carcinoma.

CONCLUSIONS: although the parameters from biexponential fitting may reflect the character of tumor cellularity, because pathological diagnosis was performed with an emphasis on cell configuration or shape rather than cellularity, it was difficult to distinguish malignant from benign tumors, including many IDPs, or to distinguish tissue types using DWI signal attenuation alone.}, } @article {pmid21187502, year = {2010}, author = {Fritz, P and Klenk, S and Goletz, S and Gerteis, A and Simon, W and Brinkmann, F and Heidemann, E and Lütttgen, E and Ott, G and Alscher, MD and Schwab, M and Dippon, J}, title = {Clinical impacts of histological subtyping primary breast cancer.}, journal = {Anticancer research}, volume = {30}, number = {12}, pages = {5137-5144}, pmid = {21187502}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*classification/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm Staging ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; }, abstract = {BACKGROUND: Treatment decisions in breast cancer depend on TNM classification and the assessment of additional variables with have an impact on survival. We examined whether histological subtyping breast cancer as either ductal or lobular is related to disease outcome.

PATIENTS AND METHODS: We examined a large data base of 14198 breast cancer patients.

RESULTS: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. However, the data further showed that invasive lobular carcinomas have a higher probability of being oestrogen receptor (ER)- and progesterone receptor (PR)-positive and a lower probability of being c-erbB2-positive. They also showed a higher average age at the time of diagnosis in comparison with invasive ductal carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p = 0.031). The multivariable Cox regression analysis showed that ER, PR, nodal status, grade and tumour size predicted disease outcome with statistical significance, while the histological subtype (invasive ductal or lobular) was not a significant predictor of disease outcome.

CONCLUSION: Histological sub-classification of invasive breast cancer as either ductal or lobular is not correlated with disease outcome. On the other hand our data gives some indication that lobular and ductal breast cancer appear to be different biological entities.}, } @article {pmid21182127, year = {2011}, author = {Jeh, SK and Kim, SH and Kim, HS and Kang, BJ and Jeong, SH and Yim, HW and Song, BJ}, title = {Correlation of the apparent diffusion coefficient value and dynamic magnetic resonance imaging findings with prognostic factors in invasive ductal carcinoma.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {33}, number = {1}, pages = {102-109}, doi = {10.1002/jmri.22400}, pmid = {21182127}, issn = {1522-2586}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {PURPOSE: To evaluate the correlation of the mean and minimal apparent diffusion coefficient values (ADC(mean) , ADC(minimal)) and dynamic magnetic resonance imaging (MRI) findings with prognostic factors in invasive ductal carcinoma.

MATERIALS AND METHODS: A total of 107 women with invasive ductal cancer underwent breast MRI. The ADC(mean) and ADC(minimal) of the cancers were computed. MRI findings were retrospectively evaluated according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon: mass or nonmass type, mass shape, mass margin, nonmass distribution, and enhancement pattern. Histological records were reviewed for tumor size, lymph node metastasis, histologic grade, and expression of estrogen receptors (ER), progesterone receptors (PR), c-erbB-2(HER2), Ki-67, and epidermal growth factor receptors (EGFR). Correlations of ADC values and MR findings with prognostic factors were determined using the Mann-Whitney U-test and the Kruskal-Wallis test.

RESULTS: The mean ADC(minimal) was 0.78 ± 0.24 (× 10⁻³ mm² /s), and the mean ADC(mean) was 1.01 ± 0.23 (× 10⁻³ mm² /s). There was a significant correlation of the ADC(mean) value with ER expression (P = 0.027) and HER2 expression (P = 0.018). There was no significant relationship between ADC(minimal) and prognostic factors or between ADC(mean) and traditional prognostic factors, PR, Ki-67 and EGFR. The majority of the mass type lesions were less than 5 cm in size and the majority of nonmass type lesions were more than 2 cm in size (P = 0.022). The margin of mass was significantly associated with lymph node metastasis (P = 0.031), ER expression (P = 0.013), PR expression (P = 0.036), HER2 expression (P = 0.019), and EGRF expression (P = 0.041). The rim internal enhancement was significantly correlated with Ki-67 expression (P = 0.008).

CONCLUSION: The low ADC(mean) value was related to positive expression of ER and negative expression of HER2. A spiculated margin was related to a good prognosis, but rim enhancement was associated with a poor prognosis.}, } @article {pmid21177208, year = {2011}, author = {Bobin, JY and Al-Khaledi, K and Ahmad, J}, title = {Breast conservative surgery for operable invasive ductal carcinoma after neoadjuvant chemotherapy or hormonal therapy- a challenge for breast surgeon: a review based on literature and experience.}, journal = {The Gulf journal of oncology}, volume = {}, number = {9}, pages = {45-51}, pmid = {21177208}, issn = {2078-2101}, mesh = {Axilla/pathology ; Breast Neoplasms/drug therapy/pathology/*surgery ; Carcinoma, Ductal, Breast/drug therapy/pathology/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Neoadjuvant Therapy ; Sentinel Lymph Node Biopsy ; }, abstract = {UNLABELLED: Neoadjuvant chemotherapy or hormonal therapy is based on biological data and enables more patients to be treated with breast conserving surgery for locally advanced T2 and T3 without significantly increasing the rates of ipsilateral breast recurrence. Careful consideration of an optimal preoperative planning aims at accurately determining the patterns of primary tumour down staging and at the amount and location of any residual tumour in the breast, besides converting patients from mutilating surgery candidates to candidates for breast conservative procedure. The use of induction chemotherapy has the potential to improve the cosmetic results but free margins must be achieved and surgery must be planned in onco-plastic surgery. Axillary lymph node clearance is still the gold standard surgery in the treatment of the axilla. Sentinel lymph node biopsy can be done for clinically N0 patients but only in control trials.

KEYWORDS: Neoadjuvant systemic therapy, breast cancer surgery.}, } @article {pmid21176537, year = {2010}, author = {Shen, PH and Zhang, W and Zhang, YH and Zhang, HX and Fan, QX}, title = {[Expression of BCSG1-siRNA in tumor transplants of human breast cancer cell line in nude mice].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {39}, number = {10}, pages = {691-694}, pmid = {21176537}, issn = {0529-5807}, mesh = {Animals ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism ; Cell Line, Tumor ; Female ; Fibroadenoma/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasm Transplantation ; *RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/*genetics ; Random Allocation ; Transfection ; Tumor Burden ; gamma-Synuclein/*biosynthesis/genetics ; }, abstract = {OBJECTIVE: To investigate the inhibitory effects of siRNA targeting BCSG1 gene expression in tumor transplants of human breast cancer cell line in nude mice.

METHODS: Four-pairs of small interfering RNA sequences of BCSG1 were chemically synthesized and inserted into the plasmid expression vectors, and were then transfected into human breast carcinoma cell line MCF7 by liposome method. Plasmid vector with unrelated sequence was used as the vector control. Cells transfected with 4 siRNA sequences, control vector and naive FCF7 cells were transplanted into the nude mice. The tumor inhibition was analysised. Immunohistochemical SP method and semi-quantitative RT-PCR were adopted to detect the BCSG1 mRNA and protein expression, respectively. Breast tissue samples of human infiltrating ductal carcinoma, ductal hyperplasia and fibroadenoma were also used as the controls.

RESULTS: The inhibition rates of tumor growth in four BCSG1-siRNA transfected groups were remarkably higher than those of the vector control group and naive MCF7 cells (P<0.01). Compared with that of the vector control and naïve MCF7 cell group, there was a significant decrease of BCSG-1 protein expression in the four experimental groups by immuno-histochemistry staining (P<0.01). In addition, BCSG1 mRNA expression in the four groups transfected with BCSG1-siRNA were significantly less than that of the control vector group, naive MCF7 cell control group and human breast IDC (P<0.01).

CONCLUSION: BCSG1-siRNA down-regulates the expression of BCSG1 and inhibits effectively growth of the transplaned human breast cancer cell line in nude mice.}, } @article {pmid21169704, year = {2010}, author = {Williams, KJ and Cooks, JM and May, M and Peranteau, J and Reifsnider, E and Hargraves, MA}, title = {Walk together children with no wasted steps: community-academic partnering for equal power in NIH proposal development.}, journal = {Progress in community health partnerships : research, education, and action}, volume = {4}, number = {4}, pages = {263-277}, doi = {10.1353/cpr.2010.0013}, pmid = {21169704}, issn = {1557-0541}, support = {R03 CA139569-03/CA/NCI NIH HHS/United States ; }, mesh = {Community Participation/methods ; Community-Based Participatory Research/*organization & administration ; *Community-Institutional Relations ; Financing, Organized ; Health Promotion/organization & administration ; Humans ; *National Institutes of Health (U.S.) ; Organizational Case Studies ; United States ; Universities/*organization & administration ; *Walking ; }, abstract = {BACKGROUND: Community-based participatory research (CBPR) approaches equitably involve community members and researchers throughout the research process. A developing literature examines problems in CBPR partnerships, but less is written about community groups using CBPR to access university resources to address community-prioritized health concerns.

OBJECTIVE: We sought to examine issues in two stages of a National Institutes of Health (NIH)-funded CBPR partnership: (1) joint proposal preparation, and (2) grant administration.

METHODS: We used a case study approach to analyze data (partner dialogs, meeting notes, interviews, and press coverage) from a longstanding community-academic partnership.

RESULTS: The partnership received NIH Partners in Research Program funding. During joint proposal preparation, issues included (1) learning to practice operating principles, such as "talking in ways that all people can understand," (2) streamlining proposal design to facilitate communication with community members, and (3) addressing inequities inherent in community-academic budget sharing. During the administration phase, issues included (1) community partner struggles with administrative requirements, (2) inequities in indirect cost (IDC) allocations, and (3) the impact of a natural disaster.

CONCLUSION: Separately funded CBPR grants can contribute to community partner development, but make substantive demands on small, grassroots community organizations. Funders should consider taking more responsibility in developing community resources and infrastructure to ensure that grassroots community groups have the power to be equal partners. More accurate accounting of costs and benefits of CBPR to vulnerable communities should be in place to ensure communities receive adequate return on the time they invest in partnering with universities.}, } @article {pmid21164937, year = {2010}, author = {Withayachumnankul, W and Fumeaux, C and Abbott, D}, title = {Compact electric-LC resonators for metamaterials.}, journal = {Optics express}, volume = {18}, number = {25}, pages = {25912-25921}, doi = {10.1364/OE.18.025912}, pmid = {21164937}, issn = {1094-4087}, mesh = {Computer-Aided Design ; Electric Capacitance ; Equipment Design ; Equipment Failure Analysis ; *Manufactured Materials ; Miniaturization ; *Optical Devices ; *Transducers ; }, abstract = {Alternative designs to an electric-LC (ELC) resonator, which is a type of metamaterial inclusion, are presented in this article. Fitting the resonator with an interdigital capacitor (IDC) helps to increase the total capacitance of the structure. In effect, its resonance frequency is shifted downwards. This implies a decreased overall resonator size with respect to its operating wavelength. As a result, the metamaterial, composed of an array of IDC-loaded ELC resonators with their collective electromagnetic response, possesses improved homogeneity and hence is less influenced by diffraction effects of individual cells. The impact of incorporating an IDC into ELC resonators in terms of the electrical size at resonance and other relevant properties are investigated through both simulation and experiment in the microwave regime. The proposed structures can be applied to the terahertz and infrared regimes via appropriate lithographic scaling.}, } @article {pmid21163412, year = {2010}, author = {Leung, TK and Huang, PJ and Lee, CM and Chen, CS and Wu, CH and Chao, JS}, title = {Can breast magnetic resonance imaging demonstrate characteristic findings of preoperative ductal carcinoma in situ in Taiwanese women?.}, journal = {Asian journal of surgery}, volume = {33}, number = {3}, pages = {143-149}, doi = {10.1016/S1015-9584(10)60024-3}, pmid = {21163412}, issn = {0219-3108}, mesh = {Adult ; *Asian People ; Breast Neoplasms/*ethnology/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*ethnology/*pathology/surgery ; Cohort Studies ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Mastectomy ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Taiwan ; }, abstract = {OBJECTIVE: Magnetic resonance imaging (MRI) is more sensitive than mammography and sonography for breast cancer detection, but its diagnostic specificity is still being debated, and standardised criteria are lacking.

METHODS: This study used a dedicated breast MRI system with a Spiral RODEO pulse sequence, and applied postprocessing techniques including multiplanar reformation (MPR) with ductal orientation, early subtracted phase (ESP) and a postcontrast kinetic curve. We discuss the possible MRI/pathology correlations based on pathogenetic concepts. We retrospectively collected data from 13 cases of benign intraductal and early-stage malignant lesions to observe the capability of MPR, ESP and kinetic curve techniques to diagnose early lesions differentially. MRI features and pathological findings for these cases were collected.

RESULTS: Thirteen cases of ductal carcinoma in situ with MRI characteristics and pathological findings were identified. We analysed early ductal lesions, such as intraductal epithelial hyperplasia, intraductal papilloma, ductal carcinoma in situ and small focal invasive ductal carcinoma. Using MRI with MPR to demonstrate ductal orientation, we found 12 cases with a ductogram appearance and 6 with crossing-over glandular tissue. The tumour size estimated by MRI was accurate in 6 cases, but overestimated in seven.

CONCLUSION: Dedicated breast MRI with MPR, ESP and kinetic curve analyses might be helpful in defining some characteristics of early-stage malignant lesions.}, } @article {pmid21160270, year = {2010}, author = {Ikeda, M and Sonoo, H and Oota, Y and Fujii, S and Shimo, T and Miyake, A and Seki, M and Nomura, T and Yamamoto, Y and Shiiki, S and Nakashima, K and Tanaka, K and Kurebayashi, J}, title = {[A case of HER2 overexpressing advanced breast cancer with CTF therapy [cyclophosphamide, pirarubicin (THPADM), fluorouracil] showed long-term effectiveness after paclitaxel shock].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {13}, pages = {2917-2920}, pmid = {21160270}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage ; Humans ; Middle Aged ; Paclitaxel/*adverse effects ; Receptor, ErbB-2/*analysis ; Shock/chemically induced ; }, abstract = {A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II)in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.}, } @article {pmid21160269, year = {2010}, author = {Ichinose, Y and Kobayashi, T and Fujimoto, A and Uchida, S and Sasaoki, T and Goto, K}, title = {[Advanced breast cancer in a patient achieving long-term SD after letrozole administration for liver metastasis developing during anastrozole therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {13}, pages = {2913-2916}, pmid = {21160269}, issn = {0385-0684}, mesh = {Aged ; Anastrozole ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Female ; Humans ; Letrozole ; Liver Neoplasms/*drug therapy/*secondary ; Nitriles/*therapeutic use ; Triazoles/*therapeutic use ; }, abstract = {We report a 69-year-old woman with breast cancer who was effectively treated with letrozole as a second-line therapy after becoming resistant to anastrozole. Her chief complaint at presentation was back pain. Physical examination and imaging studies showed a left breast tumor with skin invasion, multiple intramammary lesions, enlarged left axillary lymph node, and multiple bone metastases. Needle biopsy revealed invasive ductal carcinoma(scirrhous carcinoma)that was ER+/PgR+/ HER2-. The administration of anastrozole and bisphosphonate for 13 months resulted in a 33% reduction of the longest diameters of the breast tumors, but a liver metastasis developed. The treatment was changed to letrozole administration from January 2007.T he optimal effect of letrozole as determined by measurement on CT images was long-term SD maintained for about 13 months. No significant side effects were observed, and the QOL was favorable.}, } @article {pmid21160267, year = {2010}, author = {Hanada, N and Tomiyama, N and Hori, K and Kusano, S and Yoshida, Y and Kawata, K and Uchino, R and Sakashita, N}, title = {[A case of recurrent breast cancer with lung metastasis resection showing four disease-free years under trastuzumab treatment].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {13}, pages = {2905-2907}, pmid = {21160267}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*secondary/surgery ; Mastectomy ; Middle Aged ; Pneumonectomy ; Trastuzumab ; }, abstract = {We report a case of recurrent breast cancer with solitary lung metastasis that has shown no recurrence with treatment by trastuzumab alone after partial resection of the right lung upper lobe. A 56-year-old woman, who presented with left breast cancer, underwent quadrantectomy and axillar lymph node dissection in March 2004. Pathological findings were as follows: invasive ductal carcinoma, 3. 7 cm in size, histological grade 3, positive invasion of lymphatic and blood vessels, negative nodal status, negative ER/PgR status, and overexpression of HER2/ neu. She had received adjuvant radiotherapy followed by cyclophosphamide, methotrexate and fluorouracil combination chemotherapy; however, a lung nodule developed 14 months after first operation, which had grown gradually. Partial resection of the lung with thoracoscope assistance revealed metastatic lung cancer from breast cancer. Trastuzumab treatment for 6 months after second operation has maintained no recurrence for 4 years.}, } @article {pmid21160266, year = {2010}, author = {Yoshida, H and Yamamoto, D and Kanematsu, S and Tanaka, K and Ah, K}, title = {[A case of multi-drug resistant breast cancer with liver metastasis treated effectively by S-1 monotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {13}, pages = {2901-2903}, pmid = {21160266}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Drug Combinations ; Drug Resistance, Multiple ; *Drug Resistance, Neoplasm ; Female ; Humans ; Liver Neoplasms/secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Oxonic Acid/*therapeutic use ; Tegafur/*therapeutic use ; }, abstract = {We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.}, } @article {pmid21155040, year = {2011}, author = {Koo, JS and Jung, W}, title = {Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma.}, journal = {Yonsei medical journal}, volume = {52}, number = {1}, pages = {89-97}, pmid = {21155040}, issn = {1976-2437}, mesh = {Adult ; Breast Neoplasms/*metabolism ; Cadherins/metabolism ; Carcinoma, Lobular/*metabolism ; ErbB Receptors/metabolism ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry/*methods ; Keratin-5/metabolism ; Keratin-6/metabolism ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism ; Receptors, Androgen ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Vimentin/metabolism ; }, abstract = {PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts.

MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC.

RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs.

CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.}, } @article {pmid21151541, year = {2010}, author = {Purdom, M and Cibull, ML and Stratton, TD and Samayoa, LM and Romond, EH and McGrath, PC and Karabakhtsian, RG}, title = {Should Histologic Grade Be Incorporated into the TNM Classification System for Small (T1, T2) Node-Negative Breast Adenocarcinomas?.}, journal = {Pathology research international}, volume = {2011}, number = {}, pages = {825627}, pmid = {21151541}, issn = {2042-003X}, abstract = {Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade. While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data. For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on outcomes are sparse and controversial. This retrospective study analyzes clinical outcome in patients with small N0 IDC on the basis of tumor grade. Our results suggest that the grade does not impact clinical outcome in T1N0 tumors. In T2N0 tumors, however, it might be prognostically significant and relevant in influencing decisions regarding the need for additional adjuvant therapy and optimal management.}, } @article {pmid21148487, year = {2011}, author = {Tognon, CE and Somasiri, AM and Evdokimova, VE and Trigo, G and Uy, EE and Melnyk, N and Carboni, JM and Gottardis, MM and Roskelley, CD and Pollak, M and Sorensen, PH}, title = {ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway.}, journal = {Cancer research}, volume = {71}, number = {3}, pages = {1060-1070}, doi = {10.1158/0008-5472.CAN-10-3096}, pmid = {21148487}, issn = {1538-7445}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Benzimidazoles/pharmacology ; Breast Neoplasms/*drug therapy/enzymology/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Transformation, Neoplastic ; Epithelial-Mesenchymal Transition ; Humans ; Insulin Receptor Substrate Proteins/metabolism ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Oncogene Protein v-akt/metabolism ; Oncogene Proteins, Fusion/*biosynthesis ; Pyridones/pharmacology ; Receptor, IGF Type 1/*antagonists & inhibitors/*metabolism ; Signal Transduction ; Transplantation, Heterologous ; }, abstract = {The insulin-like growth factor (IGF) 1 receptor (IGF1R) is an important therapeutic target under study in many cancers. Here, we describe a breast cancer model based on expression of the ETV6-NTRK3 (EN) chimeric tyrosine kinase that suggests novel therapeutic applications of IGF1R inhibitors in secretory breast cancers. Originally discovered in congenital fibrosarcomas with t(12;15) translocations, EN was identified subsequently in secretory breast carcinoma (SBC) which represent a variant of invasive ductal carcinoma. Because fibroblast transformation by EN requires the IGF1R axis, we hypothesized a similar dependency may exist in mammary cells and, if so, that IGF1R inhibitors might be useful to block EN-driven breast oncogenesis. In this study, we analyzed EN expressing murine and human mammary epithelial cell lines for transformation properties. Various IGF1R signaling inhibitors, including the dual specificity IGF1R/insulin receptor (INSR) inhibitor BMS-536924, were then tested for effects on three-dimensional Matrigel cell growth, migration, and tumor formation. We found that EN expression increased acinar size and luminal filling in Matrigel cultures and promoted orthotopic tumor growth in mice. Tumors were well differentiated and nonmetastatic, similar to human SBC. The known EN effector pathway, PI3K-Akt, was activated in an IGF1- or insulin-dependent manner. BMS-536924 blocked EN transformation in vitro, whereas BMS-754807, another IGIFR/INSR kinase inhibitor currently in clinical trials, significantly reduced tumor growth in vivo. Importantly, EN model systems mimic the clinical phenotype observed in human SBC. Moreover, EN has a strict requirement for IGF1R or INSR in breast cell transformation. Thus, our findings strongly encourage the evaluation of IGF1R/INSR inhibitors to treat EN-driven breast cancers.}, } @article {pmid21140366, year = {2011}, author = {Cho, HK and Park, SH and Shin, SY}, title = {Isolated optic nerve metastasis of breast cancer initially mimicking retrobulbar optic neuritis.}, journal = {European journal of ophthalmology}, volume = {21}, number = {4}, pages = {513-515}, doi = {10.5301/EJO.2010.6099}, pmid = {21140366}, issn = {1724-6016}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*secondary/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Humans ; Immunoenzyme Techniques ; Magnetic Resonance Imaging ; Mastectomy, Modified Radical ; Middle Aged ; Optic Nerve Neoplasms/diagnosis/*secondary/therapy ; Optic Neuritis/*diagnosis ; Radiosurgery ; Visual Acuity ; }, abstract = {PURPOSE: To report a pathologically confirmed case of optic nerve metastasis of breast carcinoma, which was initially misdiagnosed as a retrobulbar optic neuritis. There have been no case reports of isolated optic nerve metastasis of breast carcinoma with nonspecific initial fundus and neuroimaging findings.

METHODS: A 51-year-old woman presented with decreased visual acuity in her left eye for 15 days. She had undergone a left modified radical mastectomy 10 years earlier. The funduscopic findings were nonspecific, except for a slightly enlarged cup-to-disc ratio of 0.6 in both eyes. The brain magnetic resonance imaging (MRI) findings were nonspecific and cerebrospinal fluid (CSF) findings were also nonspecific and negative for malignant cells. Therefore, she was diagnosed with idiopathic retrobulbar optic neuritis rather than metastasis of breast carcinoma. Intravenous steroid pulse therapy was given for 3 days.

RESULTS: The left visual acuity decreased gradually, and after 2 months was light perception-negative in the left eye. Fundus findings and CSF study results were also nonspecific as the initial presentation. On the subsequent orbit MRI, diffuse enlargement and an enhancing segment of the left optic nerve was observed, which suggested metastasis to the left optic nerve. A craniotomy and biopsy of the left optic nerve was performed. The pathologic results revealed metastatic invasive ductal carcinoma of the breast. She underwent Cyberknife surgery followed by systemic chemotherapy.

CONCLUSIONS: Patients with known cancer at another site of the body who develop optic neuropathy, with or without evidence of metastasis, should be suspected to have cancer as a cause.}, } @article {pmid21140247, year = {2014}, author = {Onoe, S and Tsuda, H and Akashi-Tanaka, S and Hasebe, T and Iwamoto, E and Hojo, T and Kinoshita, T}, title = {Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {21}, number = {2}, pages = {241-245}, doi = {10.1007/s12282-010-0245-2}, pmid = {21140247}, issn = {1880-4233}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Mastectomy, Simple ; Middle Aged ; Paget's Disease, Mammary/*pathology/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.}, } @article {pmid21135965, year = {2011}, author = {Sung, KE and Yang, N and Pehlke, C and Keely, PJ and Eliceiri, KW and Friedl, A and Beebe, DJ}, title = {Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {3}, number = {4}, pages = {439-450}, pmid = {21135965}, issn = {1757-9708}, support = {K25-CA104162/CA/NCI NIH HHS/United States ; 1R33CA137673-01/CA/NCI NIH HHS/United States ; R01 CA107012-06/CA/NCI NIH HHS/United States ; 5T15LM007359/LM/NLM NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; R01 CA107012/CA/NCI NIH HHS/United States ; K25 CA104162-01/CA/NCI NIH HHS/United States ; T15 LM007359-05/LM/NLM NIH HHS/United States ; R33 CA137673/CA/NCI NIH HHS/United States ; R01 CA114462/CA/NCI NIH HHS/United States ; 2R01 CA107012-06/CA/NCI NIH HHS/United States ; K25 CA104162/CA/NCI NIH HHS/United States ; R33 CA137673-01/CA/NCI NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Breast Neoplasms/metabolism/*pathology ; Cadherins/metabolism ; Carcinoma, Ductal/metabolism/*pathology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Coculture Techniques/methods ; Collagen/pharmacology ; Collagen Type I/pharmacology ; Collagen Type IV/metabolism ; Drug Combinations ; Extracellular Matrix Proteins/pharmacology ; Female ; Fibrillar Collagens/metabolism ; Fibroblasts/cytology ; Humans ; Laminin/pharmacology ; Mice ; Mice, Nude ; Microfluidic Analytical Techniques/*methods ; Microscopy, Fluorescence, Multiphoton/methods ; Neoplasm Invasiveness/pathology ; Proteoglycans/pharmacology ; Time Factors ; }, abstract = {The transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is a critical step in breast cancer progression. We introduce a simple microfluidic 3D compartmentalized system in which mammary epithelial cells (MCF-DCIS) are co-cultured with human mammary fibroblasts (HMFs), which promotes a transition from DCIS to IDC in vitro. The model enables control of both spatial (distance-dependence) and temporal (transition from larger clusters) aspects within the microenvironment, allowing recapitulation of the in vivo environment in ways not practical with existing experimental models. When HMFs were cultured some distance (0.5-1.5 mm) from the MCF-DCIS cells, we observed an initial morphological change, suggesting soluble factors can begin the transition. However, cell-cell contact with HMFs allowed the MCF-DCIS cells to complete the transition to invasion. Uniquely, the compartmentalized platform enables the analysis of the intrinsic second harmonic generation signal of collagen, providing a label-free quantitative analysis of DCIS-associated collagen remodeling. The arrayed microchannel-based model is compatible with existing infrastructure and, for the first time, provides a cost effective approach to test for inhibitors of pathways involved in DCIS progression to IDC allowing a screening approach to the identification of potential therapeutic targets. Importantly, the model can be easily adapted and generalized to a variety of cell-cell signaling studies.}, } @article {pmid21133582, year = {2010}, author = {Ein-Dor, T and Doron, G and Solomon, Z and Mikulincer, M and Shaver, PR}, title = {Together in pain: attachment-related dyadic processes and posttraumatic stress disorder.}, journal = {Journal of counseling psychology}, volume = {57}, number = {3}, pages = {317-327}, doi = {10.1037/a0019500}, pmid = {21133582}, issn = {0022-0167}, mesh = {Adult ; Combat Disorders/diagnosis/*psychology ; Defense Mechanisms ; Female ; Humans ; Life Change Events ; Male ; Models, Psychological ; *Object Attachment ; Pain/*psychology ; Personality Inventory/statistics & numerical data ; Prisoners/*psychology ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Social Support ; Spouses/*psychology ; Stress Disorders, Post-Traumatic/diagnosis/*psychology ; Veterans/*psychology ; }, abstract = {We used actor-partner interdependence modeling to explore associations among attachment-related dyadic processes, posttraumatic stress disorder (PTSD) in war veterans, and secondary traumatic stress (STS) in their wives. A sample of 157 Israeli couples (85 former prisoners of war and their wives and a comparison group of 72 veterans not held captive and their wives) completed self-report scales assessing attachment insecurities (anxiety, avoidance) and PTSD symptoms. For both groups of veterans and their wives, attachment anxiety was associated with the severity of their own and their spouses' PTSD and STS. Avoidant attachment was associated with PTSD and STS only in couples that included a former prisoner of war. A complex pattern of associations involving avoidant attachment was observed in the actor-partner analyses of these couples. The study demonstrates that attachment-related dyadic processes play a role in the development and maintenance of PTSD in traumatized veterans and STS in their wives.}, } @article {pmid22125710, year = {2010}, author = {Kene, TS and Odigie, VI and Yusufu, LM and Yusuf, BO and Shehu, SM and Kase, JT}, title = {Pattern of presentation and survival of breast cancer in a teaching hospital in north Western Nigeria.}, journal = {Oman medical journal}, volume = {25}, number = {2}, pages = {104-107}, pmid = {22125710}, issn = {2070-5204}, abstract = {OBJECTIVES: Developing countries are experiencing demographic and epidemiologic transition and the prevalence of non-communicable diseases especially cancers which is on the increase. Breast cancer is the most common and lethal malignancy in developing countries with varying presentation. This study aims to determine the pattern of presentation and survival of breast cancer patients in North Western Nigeria.

METHODS: A five-year retrospective review of breast cancer records from 2001-2005 was conducted. Relevant information was retrieved and analyzed using statistical package for social science software. Manchester stage III and IV were classified as advance disease. Survival analysis was carried out with survival defined as the time between the date of commencement of treatment and the date of last follow-up or death.

RESULTS: Most of the patients were in the 4th and 5th decades 58 (57.4%) with a mean age of 44.5±13 years. Majority of the patients were females 99 (96.1%). One of the four males had invasive lobular carcinoma while the others presented with invasive ductal carcinoma 3 (75.0%). Most of the patients were premenopausal 62 (62.6%) and were presented late with advanced breast cancer disease 64 (62.1%). The left breast was more affected 64 (62.1%), and the upper outer quadrant was mostly involved 48 (60.7%), followed by the areola, 43(41.7%) either singly or in combination. Invasive ductal carcinoma was detected in 85 (82.5%) cases and was the predominant histological finding. Survival rate beyond 30 months was observed in 24.5% of cases and 100% for advanced and early breast cancer respectively, (p=0.0001). The overall survival rate beyond 36 months was 70.4% and postmenopausal patients (70.6%) had better survival beyond 36 months than premenopausal (68.5%) patients (p=0.05).

CONCLUSION: The overall survival rate was low and patients with early breast cancer had better survival than those with advanced disease. Majority of the patients were young premenopausal women with advanced breast cancer.}, } @article {pmid22930617, year = {2010}, author = {Chintamani, and Rekhi, B and Bansal, A and Bhatnagar, D and Saxena, S}, title = {Expression of E-Cadherin in breast carcinomas and its association with other biological markers - a prospective study.}, journal = {Indian journal of surgical oncology}, volume = {1}, number = {1}, pages = {40-46}, pmid = {22930617}, issn = {0975-7651}, abstract = {CONTEXT: E-cadherin (E-CD) is an important cell adhesion molecule in normal epithelial cells and has been shown to be an invasion tumor suppressor gene.

MATERIALS AND METHODS: Various clinicopathological parameters like age, family history, tumor stage, histological grade, lymph node status and other biological markers were also analyzed. Present study reveals E-CD expression in 65 cases of breast cancer including 41 (63%) cases of pure infiltrating ductal carcinoma (IDC), 11 (16.9%) of pure infiltrating lobular carcinoma (ILC); another 10 (15.3%) of mixed ductal/lobular type, and remaining 3 (4.6%) miscellaneous types.

RESULTS: Negative E-CD expression was noticed more in advancing age groups (P = 0.01). About 59.2% cases showing negative E-CD expression had family history of breast and/or other cancers. E-CD expression was found significantly higher in cases of pure IDC (55.5%) than in pure ILC cases (18.1%) (P = 0.04). Eleven (68.7%) of the total 16 high-grade IDC cases, revealed negative expression. Both cases of comedo carcinoma revealed negative expression. Three (30%) out of 10 mixed cases revealed negative expression in both ductal and lobular areas, while in remaining 7 cases, positvity was seen in ductal areas only. Invasive cribriform and medullary carcinoma revealed a stronger expression, while negative staining was observed in sweat gland carcinoma. E-CD re-expression was noticed in lymph node tumor deposits. A direct association of E-CD expression with ER expression and an inverse association with that of p53 were also observed (P = 0.001), (P = 0.04).

CONCLUSIONS: E-CD expression is useful, but limited, in differentiating IDCs from ILCS. Its negative expression correlates with certain poor prognostic parameters reflecting its use as a marker for invasive cancers. It re-expresses at metastatic sites.}, } @article {pmid22767367, year = {2010}, author = {Fernandes, R}, title = {Metastatic disease causing unilateral isolated hypoglossal nerve palsy.}, journal = {BMJ case reports}, volume = {2010}, number = {}, pages = {}, pmid = {22767367}, issn = {1757-790X}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Lobular/*secondary/surgery ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Hypoglossal Nerve Diseases/*etiology/pathology/therapy ; Liver Neoplasms/pathology/therapy ; Lung Neoplasms/pathology/therapy ; Magnetic Resonance Imaging/methods ; Mammaplasty ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local/pathology/*surgery ; Neoplasms, Multiple Primary/*pathology/surgery ; Risk Assessment ; }, abstract = {The authors present the case of a middle-aged woman diagnosed with lobar carcinoma in situ in her right breast. She eventually underwent a mastectomy and reconstruction. Histology revealed grade II invasive ductal carcinoma and she was commenced on adjuvant letrozole. The following year a MRI scan revealed she had developed spinal metastases and CT confirmed the presence of liver and lung metastases. She presented with a 5-month history of tongue weakness and difficulty manipulating food to the back of her mouth. On examination, there was marked right-sided hemiatrophy of the tongue with deviation of the tongue to the right side upon protrusion. MRI demonstrated ill-defined enhancing material close to the intracranial opening of the right hypoglossal canal. The patient was referred for consideration of radiotherapy. Due to the comorbidities of the patient, she was not a candidate for neurosurgical intervention.}, } @article {pmid22242072, year = {2010}, author = {Joyce, D and O'Donoghue, G and Kerin, M}, title = {Metastatic breast disease: an all too common cause of back pain.}, journal = {BMJ case reports}, volume = {2010}, number = {}, pages = {}, pmid = {22242072}, issn = {1757-790X}, abstract = {A 50-year-old multiparous woman presented with a 3 month history of back pain. She was initially treated for non-mechanical back pain by her primary care physician, but was subsequently discovered to have a right sided clinical breast cancer and palpable axillary lymphadenopathy. An oestrogen/progesterone receptor positive invasive ductal carcinoma with axillary metastatic disease was confirmed on breast clinic triple assessment. Magnetic resonance imaging of the spine revealed an L1 vertebral body metastatic fracture with cord compression and other axial and non-axial stable skeletal metastases. The patient underwent immediate orthopaedic spinal stabilisation with full resolution of her back pain, and began primary endocrine breast cancer therapy with outpatient spinal radiotherapy planned.}, } @article {pmid22072120, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {8}, number = {6}, pages = {319-330}, doi = {10.3233/CBM-2011-0221}, pmid = {22072120}, issn = {1875-8592}, mesh = {Asian People ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/ethnology/genetics/*metabolism ; Carcinoma, Ductal, Breast/ethnology/genetics/*metabolism ; China/ethnology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Hydrophobic and Hydrophilic Interactions ; India/ethnology ; Malaysia ; Neoplasm Proteins/genetics/*metabolism ; }, abstract = {Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.}, } @article {pmid21972709, year = {2010}, author = {Gabrovski, N and Poptodorov, G and Velinov, N and Gabrovski, S}, title = {[Late metastases from breast cancer--report of two cases].}, journal = {Khirurgiia}, volume = {}, number = {1}, pages = {62-66}, pmid = {21972709}, issn = {0450-2167}, mesh = {Adult ; Brain/*pathology/*surgery ; Brain Neoplasms/pathology/*secondary/*surgery ; Breast/pathology/surgery ; Breast Neoplasms/*pathology/surgery/therapy ; Carcinoma, Ductal, Breast/*pathology/surgery/therapy ; Female ; Follow-Up Studies ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {INTRODUCTION: Breast cancer is amongst the commonest reasons for brain metastases involving 15-20% of the patients. Metastases discovered 10 or more years after the initial diagnosis of breast cancer are defined as late metastases and present a rare event. We present two cases of late brain metastases of breast cancer discovered 15 and 17 years after initial diagnosis.

MATERIALS AND METHODS: In a 46-year old female patient a 5 x 6 cm lesion in the breast was observed and was histologically diagnosed to be a breast invasive ductal carcinoma. Mastectomy was performed (TNM grade - T2N1bM0) with postoperative radiotherapy (40 Gy for 20 days) combined with chemotherapy. All control investigations were normal for the next 17 years. During the last examination CA-15-3 levels were raised. CT scan revealed a lesion involving the frontal, temporal and parietal bones and the adjacent soft tissues as well as dura mater and the subdural space. Gross total resection was performed. In a 38-year old female patient a 3 cm lesion in the breast was observed and was histologically diagnosed to be a low differentiated invasive ductal breast carcinoma. Radical mastectomy was performed TNM grade (T2N1M0) with radio- and chemotherapy. For 13 years all control markers were negative. Last examination demonstrated increase of CA-15-3 levels. Due to complain of headache and nausea CT scan was performed showing a tumor lesion in the right frontal lobe. Gross total resection was performed.

CONCLUSION: In the presented cases we describe late brain metastasis from breast cancer 15 and 17 years after initial diagnosis. This observation is important because, regular followup for patients with breast cancer is 6-10 years. Obviously this approach in clinical practice could lead to mistakes and misdiagnosis of these rare lesions. Based on our experience we suggest that the follow-up, in patients treated for breast cancer, even with apparently total regression of the disease, should be extended beyond the routine period of 10 years and tumour markers should be investigated regularly. Metastasis in CNS should be taken into consideration in patients treated for breast cancer no matter the time from the initial diagnosis when clinical symptoms appear.}, } @article {pmid21429243, year = {2010}, author = {Harkins, LE and Matlaf, LA and Soroceanu, L and Klemm, K and Britt, WJ and Wang, W and Bland, KI and Cobbs, CS}, title = {Detection of human cytomegalovirus in normal and neoplastic breast epithelium.}, journal = {Herpesviridae}, volume = {1}, number = {1}, pages = {8}, pmid = {21429243}, issn = {2042-4280}, abstract = {INTRODUCTION: Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host1. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium.

METHODS: Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids.

RESULTS: We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009).

CONCLUSIONS: These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process.}, } @article {pmid21503175, year = {2009}, author = {Ntekim, A and Nufu, FT and Campbell, OB}, title = {Breast cancer in young women in Ibadan, Nigeria.}, journal = {African health sciences}, volume = {9}, number = {4}, pages = {242-246}, pmid = {21503175}, issn = {1729-0503}, mesh = {Adult ; Age Distribution ; Age of Onset ; Breast Neoplasms/classification/epidemiology/*pathology/therapy ; Carcinoma/classification/epidemiology/*pathology/therapy ; Female ; Hospitals, Teaching ; Humans ; Neoplasm Staging ; Nigeria/epidemiology ; Prognosis ; Socioeconomic Factors ; Survival Rate ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: This study was designed to determine the clinical and socio economic features of breast cancer in young females aged 40 years and below treated at the Radiotherapy Department of The University College Hospital, Ibadan Nigeria.

METHODS: Records of female patients treated for breast cancer from 2003 to 2006 were reviewed. Records of patients aged 40 years and below were sorted out for further review. Information not available in the records was collected during follow up visits from the patients.

RESULTS: A total of 763 cases were evaluated out of which 221 (28.96 %) were 40 years and below. Stage 1 disease was diagnosed in 5 (2%) of the patients while 29 (13%) had stage 11 disease. Stages 111 and 1V were diagnosed in 102 (46%) and 85(39%) of the patients respectively. Invasive ductal carcinoma was the predominant histological type diagnosed in 210(95%) of the cases. Only 5(2%) of the patients had positive family history of breast cancer and 189 (85%) were income earners, out of these, 132(70%) had monthly income less than 12,500.00 Nigerian Naira (∼100USD). The number of young patients who were married was 166 (75%) but 6 (4%) of the married ones had no children while the rest had at least one child. Sexual dysfunction in form of loss of libido was recorded in 77 (46%) of the married patients. All the patients had primary school education while 188 (85%) had secondary school education or above. The only source of financial support received by all the patients towards their treatment was from relatives.

CONCLUSION: This study shows that we have a higher proportion of young females with breast cancer in our environment than in developed countries. Most of them present late and majority of the patients have very low income. Physicians should pay serious attention to breast lumps in young females and free health care services for these patients can promote early access to treatment.}, } @article {pmid21475922, year = {2009}, author = {Guan, H and Sun, Y and Zan, Q and Xu, M and Li, Y and Zhou, J and He, E and Eriksson, S and Wen, W and Skog, S}, title = {Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management.}, journal = {Molecular medicine reports}, volume = {2}, number = {6}, pages = {923-929}, doi = {10.3892/mmr_00000193}, pmid = {21475922}, issn = {1791-3004}, abstract = {Thymidine kinase 1 (TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 and PCNA in breast, lung and colorectal carcinoma. In this study, we extend the work of prior breast carcinoma studies by investigating the expression of TK1 in 132 patients with usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). TK1 and Ki-67 expression were determined with monoclonal antibodies using the SP technique. The expression of TK1 was found to be significantly increased in the breast ductal carcinomas in the following manner: UDH
AIM: This study has been done to evaluate comparatively the cytologic and histomorphologic grading of infiltrating ductal carcinoma of breast with specific reference to lymph node metastasis and its role in prognostication.

MATERIALS AND METHODS: Forty three patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were cytologically and histologically graded (employing Robinson's cytologic grading system and Elston's modification of Bloom-Richardson system, respectively). Statistical analysis was done employing 'z' test and χ(2) test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases, graded cyto-histologically were also evaluated for presence or absence of metastasis to the regional lymph nodes employing χ(2) test.

RESULTS: With histologic grade taken as the standard, cytology was found to be fairly comparable, for grading breast carcinoma (overall sensitivity 89.1%, specificity 100%). Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histologic grading was insignificant in all the three grade (P > 0.05). Of the six parameters studied, cell dissociation, nucleoli and chromatin pattern were the most influential features (P < 0.001). The statistically significant difference (p < 0.001) was found in incidences of axillary lymph node metastatic rate in three cytologic grades (15.4% in grade I vs. 83.3% in grade III) as well.

CONCLUSIONS: Apart from being simple and noninvasive, cytologic grading is comparable to histologic grading and might provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting mode of therapy and to predict tumor behavior.}, } @article {pmid21495363, year = {2009}, author = {Matei, M and Azoicăi, D}, title = {[Histopathological characteristics of genital and breast cancer included in epidemiologic study cohort].}, journal = {Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi}, volume = {113}, number = {2}, pages = {540-548}, pmid = {21495363}, issn = {0048-7848}, mesh = {Adenocarcinoma/epidemiology/pathology ; Adult ; Aged ; Breast Neoplasms/diagnosis/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Squamous Cell/epidemiology/pathology ; Cohort Studies ; Endometrial Neoplasms/epidemiology/pathology ; Female ; Genital Neoplasms, Female/diagnosis/*epidemiology/*pathology ; Humans ; Incidence ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/epidemiology/pathology ; Prognosis ; Risk Factors ; Romania/epidemiology ; Uterine Neoplasms/epidemiology/pathology ; }, abstract = {UNLABELLED: The correct management of genitals and breast cancers and the improving of the preventional and therapeutical successes ratio involve the knowledge of the histopathological features of these nosological entities which have different origins, different risk factors, different simptomatology and also different prognosis.

AIM: The descriptive evaluation of the histopathological features of the genitals and breast cancers to women from North-Eastern region of Romania.

MATERIAL AND METHOD: We have been included in the study 96 women (age range 23-77 years, mean 54,49) diagnosed with breast cancer, ovarian cancer, endometrial cancer and cervical cancer at the hospital admission, residency in the Obstetrics and Gynecology Clinics within 23 months. The following main parameters were assessed: histological types, stage at diagnosis, Pap test. After data collection, these have been codified and included in a MS Excel Database, in order to be processed with SPSS 16 and EpiInfo 3.5.1. (2008) Softwares.

RESULTS: The following cases' repartition on diagnostic types was observed: breast cancer (44 cases), cervical cancer (24 cases), endometrial cancer (16 cases) and ovarian cancer (12 cases). In our study, the most affected range of age was 40-69 years for breast cancer, 30-59 years for cervical cancer, over 6 years for endometrial cancer and 50-59 years for ovarian cancer. For the cervical neoplasia, 40% of analyzed cases were in incipient stages (in situ to IB stage lessions). More than 50% of breast cancer cases have been diagnosed in advances stages (IIB to IIIC stages). For the endometrium carcinoma, 45% of cases have been identified in incipient stages (in situ to IC). The ovarian neoplasia cases have been detected, most frequently, in advanced stages (III and IV). 25% of women which participated in our study had showed cervical changes.

CONCLUSION: From a histopathological point of view, for cervical neoplasia, squamous carcinoma was the most frequent type (87%), for breast neoplasia--invasive ductal carcinoma (80%) and for ovary and endometrium malignant tumors--adenocarcinoma (69%, respectively 83%).}, } @article {pmid22029443, year = {2009}, author = {Katz-Navon, TY and Goldschmidt, C}, title = {Goal orientations in negotiations: the influence of goal orientations on fixed-pie perceptions and bargaining outcomes.}, journal = {International journal of psychology : Journal international de psychologie}, volume = {44}, number = {1}, pages = {60-70}, doi = {10.1080/00207590701448012}, pmid = {22029443}, issn = {1464-066X}, mesh = {*Achievement ; Adult ; Awareness ; *Conflict, Psychological ; *Culture ; Female ; *Goals ; Humans ; Individuality ; Israel ; Male ; Motivation ; *Negotiating ; Psychological Theory ; Psychometrics ; *Social Perception ; Social Values ; Surveys and Questionnaires ; }, abstract = {As is the case for other achievement situations, people may approach negotiations emphasizing outcome and/or process goals. This paper examines the effects of process goal orientation (PGO) and outcome goal orientation (OGO) on individuals' fixed-pie perceptions and the negotiation of joint outcomes. Process and outcome goal orientations are associated with different personal beliefs about the world. We hypothesized that persons who are primarily oriented toward outcome goals, based on their fixed-entity perception of the world, would mainly concentrate on the final results or on the outcomes of the negotiation. They would tend to perceive negotiations as fixed, zero-sum, competitive situations, which have to be "won" by one of the parties at the expense of the other. On the other hand, we predicted that people who are strongly process-oriented, based on their malleable-entity perception of the world, would focus mainly on formulating and mastering the best strategies that lead to successful resolution of the negotiation. They would perceive positions to be "malleable" and, hence, would tend to perceive the negotiation as a non zero-sum situation. Additionally, the interaction between the two types of goal orientations and its effect on the parties' joint negotiation outcomes was examined. Results of two empirical studies indicated that OGO was significantly positively associated with fixed-pie bias (Study 1). The significant interaction between PGO and OGO (Study 2) demonstrated that a strong OGO combined with a strong PGO led to the best joint negotiation outcomes. Implications for goal orientation and negotiation theories are discussed.}, } @article {pmid24150552, year = {2009}, author = {Oliveira, LF and Matta, TT and Alves, DS and Garcia, MA and Vieira, TM}, title = {Effect of the shoulder position on the biceps brachii emg in different dumbbell curls.}, journal = {Journal of sports science & medicine}, volume = {8}, number = {1}, pages = {24-29}, pmid = {24150552}, issn = {1303-2968}, abstract = {Incline Dumbbell Curl (IDC) and Dumbbell Preacher Curl (DPC) are two variations of the standard Dumbbell Biceps Curl (DBC), generally applied to optimize biceps brachii contribution for elbow flexion by fixing shoulder at a specific angle. The aim of this study is to identify changes in the neuromuscular activity of biceps brachii long head for IDC, DPC and DBC exercises, by taking into account the changes in load moment arm and muscle length elicited by each dumbbell curl protocol. A single cycle (concentric-eccentric) of DBC, IDC and DPC, was applied to 22 subjects using a submaximal load of 40% estimated from an isometric MVC test. The neuromuscular activity of biceps brachii long head was compared by further partitioning each contraction into three phases, according to individual elbow joint range of motion. Although all protocols elicited a considerable level of activation of the biceps brachii muscle (at least 50% of maximum RMS), the contribution of this muscle for elbow flexion/extension varied among exercises. The submaximal elbow flexion (concentric) elicited neuro muscular activity up to 95% of the maximum RMS value during the final phase of IDC and DBC and 80% for DPC at the beginning of the movement. All exercises showed significant less muscle activity for the elbow extension (eccentric). The Incline Dumbbell Curl and the classical Dumbbell Biceps Curl resulted in similar patterns of biceps brachii activation for the whole range of motion, whereas Dumbbell Preacher Curl elicited high muscle activation only for a short range of elbow joint angle. Key pointsThe Incline Dumbbell Curl and the Dumbbell Biceps Curl resulted in a considerable neuromuscular effort throughout the whole elbow range of motion.The Incline Dumbbell Curl and the Dumbbell Biceps Curl may be preferable for the improvement of biceps brachii force in training programs.}, } @article {pmid24149527, year = {2009}, author = {Schnitzler, C and Seifert, L and Chollet, D}, title = {Variability of coordination parameters at 400-m front crawl swimming pace.}, journal = {Journal of sports science & medicine}, volume = {8}, number = {2}, pages = {203-210}, pmid = {24149527}, issn = {1303-2968}, abstract = {This study examined the variability of physiological, perceptual, stroke and coordination parameters in both genders during several swim trials at the 400-m pace speed. Twelve national level competitors (6 men, 6 women) swam 400-m at maximal speed. They then swam three additional trials (100, 200 and 300-m) at the pace (speed) of the previous 400-m. Three cameras were used to determine stroke cycle [speed (V), stroke length (SL), stroke rate (SR)] and coordination [index of coordination (IdC), stroke phases] parameters. Physiological [heart rate (HR) and lactate [La-] and perceptual [subjective workload (TWL)] parameters were assessed after each swim trial. Inter-trial data indicated that HR, [La-] and TWL increased significantly with the distance swum (p < 0.05). Inter-trial comparison did not show significant variation of stroke cycle and coordination parameters. Inter-lap data were examined within the 400-m and showed that V and SL decreased significantly at the beginning of the trial (p < 0.05), but IdC and SR remained unchanged (p > 0.05). Thus, despite changes in both physiological and perceptual responses consecutive to increasing fatigue, coordination parameters remained stable during an all-out 400-m freestyle swim. The examination of these parameters based on short-distance trials appears then to be valid, which offers interesting perspectives for swim testing. Key points"During a maximal 400-m, fatigue led to an increase in both physiological (heart rate and blood lactate) and perceptual (subjective workload) parameters.The consequence was a decrease in stroke length and therefore in the swimming speed.However, inter-arm coordination did not change during this aerobic task.This indicates that inter-arm coordination can be examined on the basis of short-distance trials rather than on the full distance.}, } @article {pmid22059352, year = {2009}, author = {Ghoneim, HM and Maher, S and Abdel-Aty, A and Saad, A and Kazem, A and Demian, SR}, title = {Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.}, journal = {The Egyptian journal of immunology}, volume = {16}, number = {2}, pages = {37-48}, pmid = {22059352}, issn = {1110-4902}, mesh = {Age Factors ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/*immunology/pathology/physiopathology ; Carcinoma/*diagnosis/*immunology/pathology/physiopathology ; Chemokine CCL2/metabolism ; Disease Progression ; Female ; Humans ; Immune Evasion ; Interleukin-8/metabolism ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Microenvironment ; }, abstract = {Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings.}, } @article {pmid21686476, year = {2009}, author = {Garas, G and Stacey-Clear, A and Whitaker, S and Collyer, J}, title = {An atypical presentation of breast cancer metastasis.}, journal = {BMJ case reports}, volume = {2009}, number = {}, pages = {}, pmid = {21686476}, issn = {1757-790X}, abstract = {A 78-year-old woman heard a crack in her left mandible while eating a biscuit and reported to her dentist, who urgently referred her to the oral and maxillofacial surgery department. On examination she had a lesion in the body of her left mandible, which had eroded through the lower border and caused a pathological fracture. Her past medical history included a left mastectomy and level II axillary lymph node dissection for a 27 mm grade III invasive ductal carcinoma of the left breast 9 months prior to her mandibular fracture. A transoral incisional biopsy was performed which confirmed the mandibular lesion to be an osteolytic metastasis from the breast. The metastasis was subsequently surgically removed and the remaining mandible repaired with a reconstruction plate followed by postoperative radiotherapy. The patient regained full function of her mandible and is now eating normally. She is being closely followed-up in the oncology outpatient department.}, } @article {pmid21637642, year = {2009}, author = {Fazza, AC and Sabino, FC and de Setta, N and Bordin, NA and da Silva, EH and Carareto, CM}, title = {Estimating genomic instability mediated by Alu retroelements in breast cancer.}, journal = {Genetics and molecular biology}, volume = {32}, number = {1}, pages = {25-31}, pmid = {21637642}, issn = {1415-4757}, abstract = {Alu-PCR is a relatively simple technique that can be used to investigate genomic instability in cancer. This technique allows identification of the loss, gain or amplification of gene sequences based on the analysis of segments between two Alu elements coupled with quantitative and qualitative analyses of the profiles obtained from tumor samples, surgical margins and blood. In this work, we used Alu-PCR to identify gene alterations in ten patients with invasive ductal breast cancer. Several deletions and insertions were identified, indicating genomic instability in the tumor and adjacent normal tissue. Although not associated with specific genes, the alterations, which involved chromosomal bands 1p36.23, 1q41, 11q14.3, 13q14.2, occurred in areas of well-known genomic instability in breast and other types of cancer. These results indicate the potential usefulness of Alu-PCR in identifying altered gene sequences in breast cancer. However, caution is required in its application since the Alu primer can produce non-specific amplification.}, } @article {pmid21326487, year = {2008}, author = {Van Ha, TG}, title = {Use of the Interlock Fibered IDC Occlusion System in Clinical Practice.}, journal = {Seminars in interventional radiology}, volume = {25}, number = {1}, pages = {3-10}, pmid = {21326487}, issn = {0739-9529}, abstract = {The use of coils in embolotherapy has been extensively described. Many different types of coils are commercially available for use. In 2006, the Interlock Fibered IDC Occlusion System (Boston Scientific, Natick, MA) was introduced to clinical practice. In this article, embolotherapy with coils in general is discussed, and the use of the Interlock coils in particular is described in different clinical scenarios.}, } @article {pmid21655368, year = {2008}, author = {Bratthauer, GL and Strauss, BL and Barner, R}, title = {Reversed Expression of the JAK/STAT Pathway Related Proteins Prolactin Receptor and STAT5a in Normal and Abnormal Breast Epithelial Cells.}, journal = {Breast cancer : basic and clinical research}, volume = {1}, number = {}, pages = {7-14}, pmid = {21655368}, issn = {1178-2234}, abstract = {The JAK/STAT pathway is important for cellular metabolism. One component, STAT5a, is activated in the breast upon prolactin to prolactin receptor (PRLR) binding facilitating the transcription of genes involved in lobule development. STAT5a was previously found to be expressed in most normal breast epithelial cells but not in many in situ or invasive carcinomas except secretory carcinomas which retain STAT5a expression. This report examines the JAK/STAT pathway in the breast through the detection of PRLR and STAT5a. Fifty breast tissues, including benign secretory change, microglandular adenosis, usual and atypical hyperplasia and in situ and invasive ductal carcinoma both usual and secretory, were obtained from the files of the Armed Forces Institute of Pathology. Sections were immunostained with antibodies to PRLR and STAT5a. PRLR was minimally detected on the surface of a few normal breast epithelial cells whereas STAT5a was greatly expressed in over 80% of normal cell nuclei. PRLR was also minimally detected in secretory carcinomas expressing STAT5a. However, the opposite pattern was seen in breast carcinomas lacking STAT5a expression. PRLR was abundantly expressed in these cells. This reversed expression may indicate a JAK/STAT pathway disturbance that could play a role in the initiation or maintenance of an abnormal breast phenotype.}, } @article {pmid21475451, year = {2007}, author = {Younis, LK and El Sakka, H and Haque, I}, title = {The Prognostic Value of E-cadherin Expression in Breast Cancer.}, journal = {International journal of health sciences}, volume = {1}, number = {1}, pages = {43-51}, pmid = {21475451}, issn = {1658-3639}, abstract = {BACKGROUND: Breast cancer continues to be a major cause of morbidity and mortality throughout the world. The behavior of breast cancer varies widely. Several parameters have been investigated to predict the prognosis in breast cancer. But still there is no single parameter that can predict prognosis in an individual patient. Among the novel prognostic markers is E-cadherin; a calcium-dependent epithelial cell adhesion molecule. Its loss has been associated with metastases, thereby providing evidence for its role as an invasion suppressor. The objective of the present study was to assess the prognostic value of E-cadherin expression in breast cancer cases, and its correlations with the other studied prognostic parameters.

METHODS: The study comprised 54 breast cancer patients admitted at King Fahd Specialist Hospital, Qassim during the period 2001-2006. The median tumor size was 3cms. Fifty cases (92.6%) had invasive ductal carcinoma, four cases had lobular carcinomas, and most were grade II (82%), stage II (48%), and the majority of cases had positive axillary lymph nodes (70.3%). Representative sections from formalin-fixed paraffin embedded tissue blocks were taken from the 54 cases of breast cancer, and were stained for E-cadherin expression by immunohistochemical technique (monoclonal E-cadherin (NCL-E-cad), Novocastra). All the lobular carcinoma cases were negative for membranous expression of E-cadherin while 72% of invasive ductal carcinomas were positive for the marker.

RESULTS: A significant correlation was found between strong E-cadherin expression and node negative cases. Node negative cases were found to be an independent predictor of strong E-cadherin expression while node positive cases predicted negative expression of E-cadherin (P = 0 .026). Also loss of E-cadherin was noted in advanced stages of breast cancer supporting the view that loss of E-cadherin expression is a marker of aggressiveness. However, there was no correlation between the E-cadherin and other prognostic parameters as tumor size, tumor grade, ER, PR, and HER-2 expression.

CONCLUSION: A significant correlation was found between strong E-cadherin expression and node negative cases.}, } @article {pmid23570163, year = {2005}, author = {Vakkila, J and DeMarco, RA and Lotze, MT}, title = {Imaging analysis of STAT1 and NF-kappaB translocation in dendritic cells at the single cell level.}, journal = {Drug discovery today}, volume = {Suppl}, number = {}, pages = {19-30}, pmid = {23570163}, issn = {1359-6446}, mesh = {Active Transport, Cell Nucleus ; Dendritic Cells/*metabolism ; Electrophoretic Mobility Shift Assay ; Flow Cytometry ; Humans ; Interferon-gamma/pharmacology ; Interleukin-1/pharmacology ; NF-kappa B/*metabolism ; Protein Transport ; STAT1 Transcription Factor/*metabolism ; *Single-Cell Analysis ; }, abstract = {Rapid assessment of immune or stem cells, which are now widely applied in the clinical setting of cancer treatment, is necessary to speed their development and to determine their quality. We have evaluated immature dendritic cells (iDC) by semiautomated imaging cytometry which provides detailed assessment at a single cell level. Nuclear translocation of NF-kappaB was studied by imaging analysis as well as electrophoretic mobility shift assay with an excellent correlation (r = 0.981) over a broad range of lipopolysaccharide (LPS) concentrations. Imaging analysis was time saving (5 h vs. 3 days), and required 30- to 100-fold less cells per analysis. Single cell information revealed remarkable heterogeneity between individual iDC and permitted detection of responses to 40 pg/ml of LPS. In IL-1beta/IFNgamma activated iDC, STAT1 responses preceded NF-kappaB responses, and the expression of both was strongly correlated in individual cells (p < 0.001). IFNgamma amplified IL-1-induced NF-kappaB responses. NF-kappaB responses to IL-1beta, CD40L, and LPS were donor-dependent (n = 7), correlated with the quality of iDC preparations (p = 0.002), and IL-12 p70 production (p = 0.010). NF-kappaB measurements in iDC within mixed cell cultures (iDC, NK, K562) demonstrated that these strategies are applicable for analyses of complex cell-cell interactions. Imaging analysis is a method that could be valuable for quality control of cell therapy preparations.}, } @article {pmid21644718, year = {1998}, author = {Fernández-Escobar, I and Gibert, M and Messeguer, A and Bayona, JM}, title = {Complete elimination of interferences in the organotin determination by oxidation with dimethyldioxirane combined with alumina cleanup.}, journal = {Analytical chemistry}, volume = {70}, number = {17}, pages = {3703-3707}, doi = {10.1021/ac980259o}, pmid = {21644718}, issn = {0003-2700}, abstract = {Most of the analytical procedures used in organotin (OT) speciation from sediment involves the Grignard derivatization reaction followed by a cleanup step and a desulfuration reaction since sulfur and/or sulfur species interfere with OT determination by GC/MS or GC-FPD. However, alkyl sulfides are generated from the coextracted elemental sulfur, and they are not removed by conventional desulfurization procedures. We propose here a method based on the oxidation of all the sulfur species with dimethyldioxirane (DMD) to sulfones or sulfur oxides. While sulfones are easily eliminated by alumina adsorption chromatography because they have higher polarity than OTs, the sulfur oxides are spontaneously evaporated. The DMD chemoselectivity favors the oxidation of sulfur compounds to sulfones in a few minutes, whereas OTs remain unreacted. In addition, the excess DMD is easily removed by evaporation under a nitrogen stream before the Al(2)O(3) cleanup step. The effectiveness of the desulfurization reaction combined with the cleanup step is demonstrated for a variety of sediment samples containing up to 3.1% of elemental sulfur, which is completely removed by adding 0.6 molar equiv of DMD. No statistical differences in the OT distribution pattern throughout the DMD intermediate oxidation steps were observed.}, } @article {pmid21528342, year = {1997}, author = {Schonborn, I and Zschiesche, W and Behrens, J and Herrenknecht, K and Birchmeier, W}, title = {Expression of E-cadherin/catenin complexes in breast cancer.}, journal = {International journal of oncology}, volume = {11}, number = {6}, pages = {1327-1334}, doi = {10.3892/ijo.11.6.1327}, pmid = {21528342}, issn = {1019-6439}, abstract = {Expression of E-cadherin, alpha-, beta- and gamma-catenins were studied in 100 patients with primary breast cancer compiled of 57 invasive ductal carcinomas (IDC) and 43 invasive lobular carcinomas (ILC) by means of immunohistochemistry. Loss of E-cadherin was observed in 26 (45.6%), and alpha-, beta- and gamma-catenin expression was lacking in 22 (38.6%), 27 (47.4%) and 22 (38.6%) IDCs, respectively. The expression in ILCs was significantly lower, as compared to IDCs (p<0.001). Immunostaining of both E-cadherin and catenins was completely lacking in 27 (47.4%) IDCs and 30 (93.8%) ILCs. Go-expression of E-cadherin/beta-catenin or E-cadherin/gamma-catenin was preserved more frequently than that of E-cadherin/alpha-catenin complexes. E-cadherin/catenin complex expression showed significant positive correlation with histological differentiation (p=0.037), ER (p=0.017) and PR expression (p=0.052), and negative correlation with c-erbB-2 receptor overexpression (p=0.046). Patients with tumours showing adhesion complexes containing alpha-catenin had an increased overall survival rate compared to other patients. Expression of either E-cadherin or alpha-catenin only, without the formation of entire adhesion complexes, was not correlated with overall survival. Thus, determination of both E-cadherin and catenins is suggested to add further information to estimate the prognosis of breast cancer patients.}, } @article {pmid21607496, year = {1994}, author = {Martinazzi, M and Zampatti, C and Crivelli, F and Zampieri, A and Martinazzi, S}, title = {Scarff-bloom-richardson histoprognostic grading correlates with the immunohistochemical expressions of genomic alterations in infiltrating ductal carcinomas (nos) of the breast.}, journal = {Oncology reports}, volume = {1}, number = {6}, pages = {1087-1091}, doi = {10.3892/or.1.6.1087}, pmid = {21607496}, issn = {1021-335X}, abstract = {The Scarff-Bloom-Richardson (SBR) multiparametric histological grading has been correlated with the immunohistochemical expression of EGF-R, c-erbB-2 and p53 oncoproteins, with the growth fraction (Ki67 antibody) and with the receptor status (ER, PgR) in 365 infiltrating ductal carcinomas of the breast (IDC-NOS). Specimens of carcinomas after surgery were sectioned and a section of each lesion was formalin-fixed and paraffin-embedded, and stained by hematoxylin-eosin in order to classify and grade cases. Another section was liquid nitrogen frozen, cryostatcut and immunostained using monoclonal antibodies against EGF-R (455 and 528 clones), c-erbB-2 (3B5 clone), p53 (Pab 1801 clone) and Ki67 antigen. An ABC-peroxidase was used after incubation with biotinylated antimouse antibody. Colour was developed using a DAB solution. ER-ICA and PgR-ICA Kits (Abbott) served to detect the hormonal receptor status. A significant direct correlation between SBR and the immuno-histochemical markers (EGF-R, c-erbB-2, p53, Ki67 growth fraction) was found. An inverse relationship of grade to ER and a weaker one to PgR was evident. An increasing histological grade was found parallel with the progressive appearance of one, two or three immunohistochemical markers in the same tumour.}, } @article {pmid21607495, year = {1994}, author = {Fujita, Y and Oyaizu, T and Hatano, T and Tsubura, A}, title = {Immunohistochemical characteristics of breast-carcinoma in patients receiving neuroleptic therapy.}, journal = {Oncology reports}, volume = {1}, number = {6}, pages = {1083-1086}, doi = {10.3892/or.1.6.1083}, pmid = {21607495}, issn = {1021-335X}, abstract = {The immunohistochemical characteristics of 17 cases of breast carcinoma in patients treated with neuroleptics (prolactin-releasing drug) are reported. Sixteen of the patients were female and one was male. Sixteen tumors in thirteen patients were invasive ductal carcinoma, two tumors in two patients were lipid-secreting carcinoma, one tumor was apocrine carcinoma, and two tumors in one patient were mucinous carcinoma. Elevated serum prolactin (Prl) levels (>15.0 ng/ml) were seen in all 7 patients whose preoperative serum prolactin levels had been determined. Immunohistochemical staining showed that 71% (15/21) of the carcinomas reacted positively for prolactin receptor (PrlR), while immunoreactive Prl was totally negative. Fourteen tumors were estrogen receptor (ER)-positive (67%; 14/21), and 12 were progesterone receptor (PgR)-positive (57%; 12/21). These results suggest that Prl secreted from the pituitary gland may interact with PrlR present on the cancer cells, but there was no evidence of de novo synthesis or uptake of Prl by cancer cells. ER and PgR status showed no characteristic immunoreactivity compared with unselected breast carcinoma patients not related to neuroleptic use.}, } @article {pmid21607403, year = {1994}, author = {Yamashita, J and Ogawa, M and Sakai, K and Tsuruta, J}, title = {A case of ductal adenoma of the breast which contains high-concentration of steroid-hormone receptors.}, journal = {Oncology reports}, volume = {1}, number = {3}, pages = {557-559}, doi = {10.3892/or.1.3.557}, pmid = {21607403}, issn = {1021-335X}, abstract = {A case of ductal adenoma of the breast in a 64-year-old Japanese woman is reported. The patient presented with a well-defined, 0.9 cm, firm mass in the right breast. Histological examination of the excised tumor revealed small and medium-sized ductules forming a nodular pattern partly surrounded by a thin layer of mature collagenous fibers. A few hyalinized fibers were also observed among the ductules, which had a clearly defined basement membrane, diagnosed as ductal adenoma of the breast. Determination of steroid hormone receptor by a dextran-coated charcoal method revealed that the ductal adenoma contained high concentration of estrogen receptor (ER) and progesterone receptor (PgR) (280 and 105 fmol/mg protein, respectively). The patient had a previous history of invasive ductal carcinoma of the left breast and had undergone a modified radical mastectomy 4 years earlier. The contralateral breast cancer was also positive for both ER and PgR (350 and 78 fmol/mg protein, respectively).}, } @article {pmid22556663, year = {1994}, author = {Karnick, CR}, title = {Some clinical observations on acne vulgaris.}, journal = {Ancient science of life}, volume = {13}, number = {3-4}, pages = {286-292}, pmid = {22556663}, issn = {0257-7941}, abstract = {The clinical similarties between the cutaneous manifestations, specially, the heper-kerototic follicular papules of hypoyitaminosis and those of Darier's disease and pity riasis, rubra pilaris, provide the rationale for the first testing Vitamin-A, as a therapy for skin diseases.Table I shows the trials taken on 125 patients, which attended our clinic, suffering from Acene, Plaques of Psoriasis Vulgaris, Psoriati arthritis and Keratinisation. These trials are taken at three different medical centres and results so obtained are recorded in this paper.}, } @article {pmid21130755, year = {2011}, author = {Zagouri, F and Sergentanis, TN and Kalogera, E and Provatopoulou, X and Chrysikos, D and Zografos, E and Bletsa, G and Flessas, I and Papadimitriou, CA and Zografos, GC and Gounaris, A}, title = {Serum MMPs and TIMPs: may be predictors of breast carcinogenesis?.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {412}, number = {7-8}, pages = {537-540}, doi = {10.1016/j.cca.2010.11.037}, pmid = {21130755}, issn = {1873-3492}, mesh = {Female ; Humans ; Matrix Metalloproteinases/*blood ; Tissue Inhibitor of Metalloproteinases/*blood ; }, abstract = {BACKGROUND: The involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions.

METHODS: On women with benign (n=65), precursor [ADH (n=18) and LN (n=15)], preinvasive [DCIS (n=32)] and invasive [IDC (n=28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10mm in diameter, as estimated on the mammographic views. Statistical analysis followed.

RESULTS: TIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup.

CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.}, } @article {pmid21130066, year = {2011}, author = {Sontimuang, C and Suedee, R and Dickert, F}, title = {Interdigitated capacitive biosensor based on molecularly imprinted polymer for rapid detection of Hev b1 latex allergen.}, journal = {Analytical biochemistry}, volume = {410}, number = {2}, pages = {224-233}, doi = {10.1016/j.ab.2010.11.043}, pmid = {21130066}, issn = {1096-0309}, mesh = {Acrylamides/chemistry ; Allergens/*analysis/*chemistry ; Antigens, Plant/*analysis/chemistry ; Biosensing Techniques/*methods ; Electric Capacitance ; Humans ; Latex Hypersensitivity/diagnosis ; Methacrylates/chemistry ; Molecular Imprinting/*methods ; Plant Proteins/*analysis/chemistry ; Polymers/*chemistry ; Pyrrolidinones/chemistry ; }, abstract = {Allergen protein detection was performed by a surface imprinted layer combined with an interdigitated capacitance (IDC) transducer that allowed label-free measurements. The immobilized imprinted polymers are the probes that bind to rubber allergen proteins extracted from products such as rubber gloves. Copolymers made from methacrylic acid-vinylpyrrolidone-dihydroxyethylene-bisacrylamide (MAA-NVP-DHEBA) are soluble in aqueous solution and eliminate the denaturation of protein. When deposited as a coating onto an IDC microelectrode transduction system, such materials lead to sensors that produce capacitance responses that are clearly dependent on the concentration of the latex protein (10-900 ng ml(-1)) in pH 7.4 buffer. The biosensor can detect Hev b1 within minutes and with a detection limit of 10 ng ml(-1). Different but related hevein allergenic proteins isolated from natural rubber latex from the rubber tree (Hev b1, Hev b2, and Hev b3) were distinguished by the imprinted material, depending on the dimension and conformation of these proteins with a selectivity factor of 4. They recognized Hevea latex proteins better than non-Hev b proteins, such as lysozyme, ovalbumin, and bovine serum albumin, by a factor of 2. Moreover, the sensor exhibited good operational stability of up to 180 days when used continuously at room temperature.}, } @article {pmid21126378, year = {2010}, author = {Jung, SY and Jeong, J and Shin, SH and Kwon, Y and Kim, EA and Ko, KL and Shin, KH and Lee, KS and Park, IH and Lee, S and Kim, SW and Kang, HS and Ro, J}, title = {The invasive lobular carcinoma as a prototype luminal A breast cancer: a retrospective cohort study.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {664}, pmid = {21126378}, issn = {1471-2407}, mesh = {Adult ; Asian People ; Biomarkers, Tumor/analysis ; Breast Neoplasms/classification/ethnology/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/classification/ethnology/mortality/*pathology/therapy ; Carcinoma, Lobular/classification/ethnology/mortality/*pathology/therapy ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Korea/epidemiology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Survival Rate ; Terminology as Topic ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known.

METHODS: We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC).

RESULTS: The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥ T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07).

CONCLUSIONS: ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.}, } @article {pmid21125683, year = {2011}, author = {Bombonati, A and Sgroi, DC}, title = {The molecular pathology of breast cancer progression.}, journal = {The Journal of pathology}, volume = {223}, number = {2}, pages = {307-317}, pmid = {21125683}, issn = {1096-9896}, support = {R01 CA112021/CA/NCI NIH HHS/United States ; R01 CA112021-02/CA/NCI NIH HHS/United States ; R01-1CA112021-02/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Profiling/methods ; Humans ; Models, Genetic ; Neoplastic Stem Cells/pathology ; }, abstract = {The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into DCIS and culminates in the potentially lethal stage of invasive ductal carcinoma. For several decades a major challenge to human breast cancer research has been the identification of the molecular alterations associated with the different stages of breast cancer progression. Until recently, progress in attaining this goal has been hampered by technical limitations associated with applying advanced molecular technologies to the microscopic preinvasive stages of breast tumorigenesis. Recent advances in comprehensive, high-throughput genetic, transcriptomic and epigenetic technologies in combination with advanced microdissection and ex vivo isolation techniques have provided for a more complete understanding of the complex molecular genetic and molecular biological inter-relationships of the different stages of human breast cancer evolution. Here we review the molecular biological data suggesting that breast cancer develops and evolves along two distinct molecular genetic pathways. We also briefly review gene expression and epigenetic data that support the view of the tumour microenvironment as an important co-conspirator rather than a passive bystander during human breast tumorigenesis.}, } @article {pmid21124126, year = {2010}, author = {Roth, FS and Felder, JM and Friedman, JD}, title = {Breast capsulectomy specimens and their clinical implications.}, journal = {Plastic and reconstructive surgery}, volume = {126}, number = {6}, pages = {1848-1852}, doi = {10.1097/PRS.0b013e3181f4463c}, pmid = {21124126}, issn = {1529-4242}, mesh = {Breast/pathology ; Breast Diseases/*pathology/*surgery ; Breast Implantation/*economics ; Breast Neoplasms/pathology/surgery ; Calcinosis/*pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Cost Savings ; Female ; Foreign-Body Reaction/*pathology/*surgery ; Granuloma, Foreign-Body/*pathology/*surgery ; Hospital Charges/statistics & numerical data ; Humans ; Neoplasm Recurrence, Local/pathology/surgery ; Pathology, Surgical/*economics ; Postoperative Complications/*pathology/*surgery ; Reoperation/economics ; Retrospective Studies ; Unnecessary Procedures/*economics ; }, abstract = {BACKGROUND: Plastic surgeons routinely submit breast capsulectomy surgical specimens for pathologic evaluation. However, clinically significant findings are rarely identified. In an effort to reduce health care costs and the unnecessary use of hospital resources, this study reviews the efficacy of submitting breast capsulectomy specimens for pathologic examination.

METHODS: All patients from The Methodist Hospital in Houston, Texas, during the years 2000 to 2008 who underwent breast capsulectomy were selected for by Current Procedural Terminology codes 19370 and 19371 (open periprosthetic capsulotomy and periprosthetic capsulectomy of the breast, respectively). A total of 264 patients qualified for the study, and their pathology reports were reviewed.

RESULTS: The pathology reports of 434 capsulectomy specimens in 264 patients revealed benign capsules in 206 patients (78.0 percent). Additional findings, including inflammation, calcification, granuloma, and necrosis, were identified in an additional 57 patients (21.6 percent). One patient (0.4 percent) had carcinoma identified within a breast capsule. This was a patient known preoperatively to have recurrent invasive ductal carcinoma that extended into the surrounding capsule. Therefore, none of the 264 capsulectomy specimens revealed new neoplasms, occult disease, or other clinically significant findings that changed the patient's postoperative treatment.

CONCLUSIONS: No clinically significant findings were identified in this review of breast capsulectomy specimens in 264 patients. However, the cost for such pathologic examinations was substantial. In an effort to reduce health costs and the unnecessary use of hospital resources, breast capsulectomy specimens may not necessarily need to be routinely submitted for surgical pathologic evaluation.}, } @article {pmid21120523, year = {2011}, author = {Park, SY and Kwon, HJ and Lee, HE and Ryu, HS and Kim, SW and Kim, JH and Kim, IA and Jung, N and Cho, NY and Kang, GH}, title = {Promoter CpG island hypermethylation during breast cancer progression.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {458}, number = {1}, pages = {73-84}, pmid = {21120523}, issn = {1432-2307}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; CpG Islands/*genetics ; DNA Methylation/genetics/*physiology ; DNA, Neoplasm/genetics/*metabolism ; *Disease Progression ; Female ; Homeodomain Proteins/metabolism ; Humans ; Hyperplasia/genetics/metabolism/pathology ; Membrane Proteins/metabolism ; Metallothionein/metabolism ; Middle Aged ; Neoplasm Proteins/metabolism ; Promoter Regions, Genetic/*genetics ; Proto-Oncogene Proteins/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retrospective Studies ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism ; }, abstract = {This study was designed to evaluate the changes in promoter CpG islands hypermethylation during breast cancer progression from pre-invasive lesions [flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS)] to invasive ductal carcinoma (IDC). We performed MethyLight analysis for the methylation status of 57 promoter CpG island loci in 20 IDCs and their paired normal breast tissues. After selecting 15 CpG island loci showing breast cancer-specific DNA methylation, another set of normal breast tissue (n = 10), ADH/FEA (n = 30), DCIS (n = 35), and IDC (n = 30) of the breast were analyzed for these loci. We found six new methylation markers of breast cancer, namely DLEC1, GRIN2B, HOXA1, MT1G, SFRP4, and TMEFF2, in addition to APC, GSTP1, HOXA10, IGF2, RARB, RASSF1A, RUNX3, SCGB3A1 (HIN-1), and SFRP1. The number of methylated genes increased stepwise from normal breast to ADH/FEA and DCIS, while IDC did not differ from DCIS. Methylation levels and frequencies of APC, DLEC1, HOXA1, and RASSF1A promoter CpG islands were significantly higher in ADH/FEA than in normal breast tissue. GRIN2B, GSTP1, HOXA1, RARB, RUNX3, SFRP1, and TMEFF2 showed higher methylation levels and frequencies in DCIS than in ADH/FEA. DICS and IDC did not differ in the methylation levels or frequencies for most CpG island loci except SFRP1 and HOXA10. Our findings showed that promoter CpG island methylation changed significantly in pre-invasive lesions, and was similar in IDC and DCIS, suggesting that CpG island methylation of tumor-related genes is an early event in breast cancer progression.}, } @article {pmid21119286, year = {2010}, author = {Rao, S and Latha, PS and Ravi, A and Thanka, J}, title = {Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.}, journal = {Journal of cancer research and therapeutics}, volume = {6}, number = {3}, pages = {385-387}, doi = {10.4103/0973-1482.73350}, pmid = {21119286}, issn = {1998-4138}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/complications/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/complications/*diagnosis/diagnostic imaging ; Diagnostic Errors ; Female ; Fibroadenoma/complications/*diagnosis/diagnostic imaging ; Humans ; Mammography ; }, abstract = {We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.}, } @article {pmid21114180, year = {2010}, author = {Munjal, K and Jain, VK and Agrawal, A and Bandi, PK}, title = {Co-existing tubercular axillary lymphadenitis with carcinoma breast can falsely over-stage the disease--case series.}, journal = {The Indian journal of tuberculosis}, volume = {57}, number = {2}, pages = {104-107}, pmid = {21114180}, issn = {0019-5707}, mesh = {Adult ; Aged ; Axilla/*microbiology ; Breast Neoplasms/*complications/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Tuberculosis, Lymph Node/*complications ; }, abstract = {The synchronous occurrence of tuberculosis and carcinoma in breast is unusual. The simultaneous occurrence of both the diseases can complicate the neoplastic disease. The diagnosis and treatment of tuberculosis in a patient with cancer assumes importance as it can prevent high mortality in patients with co-existent disease and thereby create problems in treatment decision. Axillary lymph node enlargement in breast cancer patient is not always caused by metastatic tumour of the breast even in the ipsilateral axillary nodes. We present here six case reports as an example of tuberculous axillary lymphadenitis co-existing with invasive ductal carcinoma of the breast. Accurate diagnosis has helped in down-staging carcinoma of the breast and also in identifying curable disease.}, } @article {pmid21109569, year = {2011}, author = {Yu, Q and Niu, Y and Liu, N and Zhang, JZ and Liu, TJ and Zhang, RJ and Wang, SL and Ding, XM and Xiao, XQ}, title = {Expression of androgen receptor in breast cancer and its significance as a prognostic factor.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {22}, number = {6}, pages = {1288-1294}, doi = {10.1093/annonc/mdq586}, pmid = {21109569}, issn = {1569-8041}, mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/genetics/*metabolism ; Carcinoma, Ductal, Breast/*diagnosis/genetics/metabolism ; China ; Disease Progression ; Female ; Fluorescent Antibody Technique ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Androgen/genetics/*metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer is an extraordinarily hormone-dependent tumor. This study was to evaluate androgen receptor (AR) status and its significance in breast cancer in Chinese women.

METHODS: Three hundred and thirty-five consecutive cases of invasive ductal breast carcinoma, 34 ductal carcinoma in situ (DCIS), and 82 DCIS adjacent to invasive tissues were involved in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient outcome, and its implications were evaluated in five molecular subgroups of invasive ductal carcinoma (IDC) and in DCIS lesions.

RESULTS: AR expression was related to that of estrogen receptor (P < 0.001) and progesterone receptor (P = 0.035) but not correlated with the other conventional parameters. AR retained independent prognostic significance (hazard ratio 0.309, 95% confidence interval, 0.192-0.496; P < 0.001). The majority (61.0%) of basal-like breast cancers showed loss of AR expression (P < 0.001), which had poor prognosis. The percentage of AR-positive cases was significantly higher in DCIS adjacent to IDC group than in pure DCIS and IDC groups (93.9%, 79.4%, and 72.5%; P = 0.046 and P < 0.001, respectively).

CONCLUSIONS: Our data suggest that AR may provide another specific definition of breast cancer subtypes and reveal a potential role in DCIS progression. These findings may help develop new therapies.}, } @article {pmid21107683, year = {2011}, author = {Hartog, H and Horlings, HM and van der Vegt, B and Kreike, B and Ajouaou, A and van de Vijver, MJ and Marike Boezen, H and de Bock, GH and van der Graaf, WT and Wesseling, J}, title = {Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {129}, number = {3}, pages = {725-736}, doi = {10.1007/s10549-010-1256-6}, pmid = {21107683}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/*pathology/therapy ; Cytoplasm/metabolism ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptor, IGF Type 1/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.}, } @article {pmid21106423, year = {2011}, author = {Liu, Q and Yang, YM and Zhang, QH and Zhang, TG and Zhou, Q and Zhou, CJ}, title = {Inhibitor of differentiation is overexpressed with progression of benign to malignant lesions and related with carcinoembryonic antigen-related cell adhesion molecule 1 distribution in mammary glands.}, journal = {Annals of diagnostic pathology}, volume = {15}, number = {1}, pages = {30-36}, doi = {10.1016/j.anndiagpath.2010.07.010}, pmid = {21106423}, issn = {1532-8198}, mesh = {Antigens, CD/*metabolism ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cell Adhesion Molecules/*metabolism ; Cell Transformation, Neoplastic/metabolism/pathology ; Disease Progression ; Epithelium/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Differentiation Protein 1/*metabolism ; Mammary Glands, Human/*metabolism/pathology ; Precancerous Conditions/*metabolism/pathology ; }, abstract = {The purpose of the study was to investigate the expression and association of inhibitor of differentiation (Id-1) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in benign, premalignant, and malignant lesions of human mammary glands. The study included 97 cases of benign, premalignant, and malignant lesions of human mammary glands including normal terminal duct lobular units, usual ductal hyperplasia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma that were surgically excised at the Second Hospital of Shangdong University. Immunohistochemistry was used to determine the expression of Id-1 and CEACAM1. The Id-1 expression was increased with the progression of benign to malignant transformation (P < .05) and positively related with CEACAM1 different expression patterns (r = 0.279, P < .01) in benign, premalignant, and malignant lesions: apical membranous staining in benign, and cytoplasmic and uniform membranous staining in premalignant and malignant lesions. A positive correlation was found between Id-1 expression and morphologic classification of benign to premalignant and malignant lesions (r = 0.641, P < .0001). The CEACAM1 expression patterns showed a significance between benign, premalignant, and malignant lesions (P < .05). The Id-1 expression is increased with the progression of benign to malignant transformation and promotes the CEACAM1 expression; the CEACAM1 expression patterns are changed by movement from apical membrane to bilateral membrane and cytoplasm. That the Id-1 overexpression promotes the transformation of CEACAM1 expression patterns may occur at the early stage in the breast carcinogenesis; and the Id-1 should be regarded as the transforming factor, which may regulate the transformation of CEACAM1 expression patterns.}, } @article {pmid21106422, year = {2011}, author = {Ban, S and Satoh, H and Satoh, M and Ishido, Y and Nakayama, N and Yamaguchi, H and Shimizu, M}, title = {Invasive ductal carcinoma of the pancreas tail with noninvasive growth through the nondilated main pancreatic duct and macroscopically cystic invasive carcinomatous glands.}, journal = {Annals of diagnostic pathology}, volume = {15}, number = {6}, pages = {476-480}, doi = {10.1016/j.anndiagpath.2010.08.004}, pmid = {21106422}, issn = {1532-8198}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/*pathology ; Female ; Humans ; Male ; Neoplasm Invasiveness ; Pancreatic Ducts/*pathology ; Pancreatic Neoplasms/*pathology ; }, abstract = {Noninvasive growth forming macroscopically dilated cystic pancreatic ducts is a fundamental feature of intraductal papillary mucinous neoplasm (IPMN), from which invasive carcinomas can arise. However, some invasive ductal carcinomas of the pancreas also show a macroscopically cystic feature. We experienced 2 cases of invasive ductal carcinoma of the pancreas tail with noninvasive growth through the main pancreatic duct without dilation at the body side, and with collection of macroscopically cystic carcinomatous glands infiltrating at the spleen side, which resembled some IPMNs and/or IPMN-derived invasive carcinomas. These cases were different from IPMN in that they lacked macroscopic dilatation of the pancreatic ducts, and the macroscopically dilated cystic carcinomatous glands were invasive but not intraductal. The intraductal component of the carcinomas showed papillary growth of neoplastic epithelia with atypia consistent with PanIN-3. Both intraductal and invasive components predominantly showed gastric mucin phenotype (MUC5AC+, MUC6 focally +, MUC2- or MUC2+ in scattered small number of cells). Recognition of these pancreatic carcinoma cases is important in the following 2 points: (1) The presence of such cases should always be kept in mind as differential diagnosis of IPMN or IPMN-derived invasive carcinoma in imaging and pathologic diagnoses. (2) The histogenesis of these cases might be placed in the intermediate between 2 major histogenetic pathways of pancreatic carcinoma, that is, one from microscopic precursors called PanIN and the other from macroscopic precursors of IPMN. These cases can be regarded as invasive carcinomas derived from semimacroscopic extension of the intraductal lesion of the main pancreatic duct.}, } @article {pmid21103636, year = {2010}, author = {Venter, A and Roşca, E and Muţiu, G and Pirte, A and Roşca, DM}, title = {The value of ultrasounds exam correlated with frozen section diagnosis in the breast tumors.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {51}, number = {4}, pages = {745-750}, pmid = {21103636}, issn = {1220-0522}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/*diagnosis/*diagnostic imaging/pathology ; Carcinoma in Situ/diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnosis/diagnostic imaging/pathology ; Carcinoma, Lobular/diagnosis/diagnostic imaging/pathology ; Carcinoma, Medullary/diagnosis/diagnostic imaging/pathology ; Female ; Fibroadenoma/diagnosis/diagnostic imaging/pathology ; *Frozen Sections ; Humans ; Middle Aged ; *Ultrasonography, Mammary ; Young Adult ; }, abstract = {UNLABELLED: The paper represents a parallel study regarding the harmony between the ultrasounds and the frozen section diagnosis in the breast cancer.

PATIENTS AND METHODS: We examined at an ultrasounds machine a group of 146 women aged between 16-73-year-old, which came presenting palpable formations at the level of breasts, in the Pelican Medical Centre from Oradea. The suspect lesions were subject to excisional biopsy or surgical intervention.

RESULTS: The elements followed at the ultrasounds exam were: echogenicity, echostructure, contour, presence and absence of posterior shadowing, microcalcifiation, orientation of lesion, compressibility, aspect of adjacent structures. Histopathological diagnosis of suspect lesions emphasized malignant lesions in a percentage of 64.86% of cases; the frozen section exam diagnosed invasive ductal carcinoma in 86% of the cases, invasive lobular carcinoma 8%, medullar carcinoma 2%, and benign lesions 4%.

CONCLUSIONS: The clinical-anatomopathological collaboration is absolutely compulsory for a correct microscopic diagnosis. The ultrasounds modifications separated after the criteria taken into account allow the orientation of diagnosis to malignant-benign. At 14% of the women examined, additional lesions were identified in comparison to those palpated, the ultrasounds having a role in detecting the multifocality and muticentricity of lesions. At 29.05% from the identified lesions, malignant lesions were histopathologically identified. The frozen section diagnosis in the breast cancer allows a rapid diagnosis, correct in high percentage of cases, allowing taking an intra-surgery therapeutic attitude in only one surgical intervention, thus reducing the costs. The anatomopathologist's experience reduces the diagnosis risk in excess and÷or in minus.}, } @article {pmid21095911, year = {2010}, author = {Lim, YG and Chung, GS and Park, KS}, title = {Capacitive driven-right-leg grounding in Indirect-contact ECG measurement.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2010}, number = {}, pages = {1250-1253}, doi = {10.1109/IEMBS.2010.5626424}, pmid = {21095911}, issn = {2375-7477}, mesh = {*Artifacts ; Electric Capacitance ; Electrocardiography/*instrumentation ; *Electrodes ; Equipment Design ; Equipment Failure Analysis ; Humans ; *Leg ; Monitoring, Ambulatory/*instrumentation ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {For the reduction of common-mode noise level in Indirect-contact ECG (IDC-ECG) measurement, a driven-right-leg grounding method was applied to the IDC-ECG. Because the IDC-ECG does not require any direct contact between the electrodes and the human skin, it is adequate for un-constraining long-term ECG measurement at home and its various applications are now under development. However, larger 60 Hz noise induced by power line appears in IDC-ECG than in conventional ECG, that is a restriction of IDC-ECG application. In this study, the driven-right-leg ground which has been used in conventional direct-contact ECG, was adapted to the IDC-ECG measurement, by feedback of the inversion of amplified common-mode noise to the body through the conductive textile laid on the chair seat. It was shown that the level of 60Hz power line noise was reduced to about -40 dB when the driven-right-leg gain was 1000.}, } @article {pmid21093830, year = {2010}, author = {Kuo, YJ and Ho, DM and Tsai, YF and Hsu, CY}, title = {Invasive ductal carcinoma arising in phyllodes tumor with isolated tumor cells in sentinel lymph node.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {73}, number = {11}, pages = {602-604}, doi = {10.1016/S1726-4901(10)70131-3}, pmid = {21093830}, issn = {1728-7731}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Neoplasm Invasiveness ; Phyllodes Tumor/*pathology ; *Sentinel Lymph Node Biopsy ; }, abstract = {Phyllodes tumor (PT) consists of stroma of variable grading and benign ductal epithelium. Although exceptional, carcinomas that arise from the epithelium in PTs do exist, and seem to behave less aggressively than the usually encountered breast carcinoma. To the best of our knowledge, among the invasive carcinomas that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in the lymph nodes. Here, we describe the youngest woman to have invasive ductal carcinoma that arose in a borderline PT, with isolated carcinoma cells in the sentinel lymph node. Whether such a combined lesion carries a more indolent course is also discussed.}, } @article {pmid21092179, year = {2010}, author = {Gil-Guillen, V and Orozco-Beltran, D and Redon, J and Pita-Fernandez, S and Navarro-Pérez, J and Pallares, V and Valls, F and Fluixa, C and Fernandez, A and Martin-Moreno, JM and Pascual-de-la-Torre, M and Trillo, JL and Durazo-Arvizu, R and Cooper, R and Hermenegildo, M and Rosado, L}, title = {Rationale and methods of the cardiometabolic Valencian study (Escarval-Risk) for validation of risk scales in Mediterranean patients with hypertension, diabetes or dyslipidemia.}, journal = {BMC public health}, volume = {10}, number = {}, pages = {717}, pmid = {21092179}, issn = {1471-2458}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases/*epidemiology ; Cohort Studies ; Diabetes Mellitus/*epidemiology ; Dyslipidemias/*epidemiology ; Female ; Humans ; Hypertension/*epidemiology ; Male ; Mediterranean Region ; Middle Aged ; Prospective Studies ; Risk Assessment/*methods ; }, abstract = {BACKGROUND: The Escarval-Risk study aims to validate cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia living in the Valencia Community, a European Mediterranean region, based on data from an electronic health recording system comparing predicted events with observed during 5 years follow-up study.

METHODS/DESIGN: A cohort prospective 5 years follow-up study has been designed including 25000 patients with hypertension, diabetes and/or dyslipidemia attended in usual clinical practice. All information is registered in a unique electronic health recording system (ABUCASIS) that is the usual way to register clinical practice in the Valencian Health System (primary and secondary care). The system covers about 95% of population (near 5 million people). The system is linked with database of mortality register, hospital withdrawals, prescriptions and assurance databases in which each individual have a unique identification number. Diagnoses in clinical practice are always registered based on IDC-9. Occurrence of CV disease was the main outcomes of interest. Risk survival analysis methods will be applied to estimate the cumulative incidence of developing CV events over time.

DISCUSSION: The Escarval-Risk study will provide information to validate different cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia from a low risk Mediterranean Region, the Valencia Community.}, } @article {pmid21091847, year = {2011}, author = {Souzaki, M and Kubo, M and Kai, M and Kameda, C and Tanaka, H and Taguchi, T and Tanaka, M and Onishi, H and Katano, M}, title = {Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer.}, journal = {Cancer science}, volume = {102}, number = {2}, pages = {373-381}, doi = {10.1111/j.1349-7006.2010.01779.x}, pmid = {21091847}, issn = {1349-7006}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Disease Progression ; Female ; Hedgehog Proteins/*metabolism ; Humans ; Immunohistochemistry ; Microdissection ; Neoplasm Staging ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*physiology ; }, abstract = {The purpose of this study is to clarify the contribution of the Hedgehog signaling pathway (Hh pathway) to the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). A total of 149 surgically resected mammary disease specimens and 12 sentinel lymph nodes with micro-metastasis (Ly-met) were studied. The degree of Hh pathway activation was estimated from the Gli1 nuclear staining ratio (%Gli1 nuclear translocation) in cancer cells. The invasiveness of breast cancer cells was determined using Matrigel assays. A serial increase of %Gli1 nuclear translocation to IDC from non-neoplastic diseases was confirmed. In tumor specimens, %Gli1 nuclear translocation correlated with the invasiveness of each type of mammary disease and also correlated with invasion-related histopathological parameters. The %Gli1 nuclear translocation in lymph nodes with micro-metastasis was similar to that in primary sites and higher than that in DCIS with microinvasion and DCIS. Blockade of the Hh pathway decreased the invasiveness of breast cancer cells. In IDC, %Gli1 nuclear translocation correlated with the expression of estrogen receptor-α. Estrogen increased %Gli1 nuclear translocation and the invasiveness of estrogen receptor-α-positive cells. The Hh pathway mediates progression from a non-invasive phenotype to an invasive phenotype and %Gli1 nuclear translocation may be useful as a predictive marker for evaluating the ability of invasiveness.}, } @article {pmid21091771, year = {2010}, author = {Wang, R and Li, ZQ and Han, X and Li, BL and Mi, XY and Sun, LM and Song, M and Han, YC and Zhao, Y and Wang, EH}, title = {Integrin β3 and its ligand regulate the expression of uPA through p38 MAPK in breast cancer.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {118}, number = {12}, pages = {909-917}, doi = {10.1111/j.1600-0463.2010.02687.x}, pmid = {21091771}, issn = {1600-0463}, mesh = {Adult ; Aged ; Breast Neoplasms/enzymology/*metabolism ; Carcinoma, Ductal, Breast/enzymology/*metabolism ; Cell Line, Tumor ; Cell Survival/physiology ; Chi-Square Distribution ; Enzyme Inhibitors/pharmacology ; Female ; Formazans ; Humans ; Imidazoles/pharmacology ; Immunohistochemistry ; Integrin beta3/*metabolism ; Middle Aged ; Pyridines/pharmacology ; Retrospective Studies ; Tenascin/*metabolism ; Tetrazolium Salts ; Urokinase-Type Plasminogen Activator/antagonists & inhibitors/*biosynthesis/metabolism ; p38 Mitogen-Activated Protein Kinases/*metabolism ; }, abstract = {Interplay between integrins and extracellular matrix is suggested to play an important role in malignant progression and tumor differentiation. The aim of the study was to determine the combined expression of integrin β3 and tenascin-c (TN-c) in breast cancer and examine whether integrin β3 and TN-c can activate urokinase-type plasminogen activator (uPA) through p38 mitogen-activated protein kinase (p38 MAPK). We detected the expression of integrin β3, TN-c, p-p38, and uPA in 80 cases of breast invasive ductal carcinoma by immunohistochemistry. In addition, we blocked integrin β3 and TN-c in the MDA-MB-231 breast cancer cells and detected the expression of p-p38 and uPA by Western blot. Integrin β3, TN-c, p-p38, and uPA showed high levels of expression in breast invasive ductal carcinoma. The expression of integrin β3, TN-c, and uPA was correlated with lymph node metastasis and TNM stage in breast cancer. Furthermore, correlations were noted between any two of the three proteins. The expression of p-p38 and uPA decreased in MDA-MB-231 cells after the addition of integrin β3 antibody and TN-c antibody. The expression of uPA decreased after addition of SB203580. Our results demonstrate that inhibition of the expression of integrin β3 and TN-c could decrease the expression of uPA through p38 MAPK in breast cancer, suggesting that the interaction between integrin β3 and TN-c serves an important role in breast cancer.}, } @article {pmid21084819, year = {2010}, author = {Nakamura, Y and Aono, T and Nomura, M and Iwase, K and Tanaka, Y}, title = {[Two cases of HER2-positive advanced or metastatic breast cancer, responding to lapatinib and capecitabine].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {11}, pages = {2165-2168}, pmid = {21084819}, issn = {0385-0684}, mesh = {Adenocarcinoma, Scirrhous/*drug therapy/pathology ; Aged ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage/analogs & derivatives ; Humans ; Lapatinib ; Lung Neoplasms/secondary ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Quinazolines/administration & dosage ; Receptor, ErbB-2/*analysis ; }, abstract = {The first patient was a 59-year-old woman who was diagnosed with invasive scirrhous carcinoma. The tumor was estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-positive. The patient was treated with adjuvant chemotherapy and endocrine therapy after surgery. Liver metastases developed 5 years after surgery. She was treated with trastuzumab combined with vinorelbine, paclitaxel, or docetaxel. The liver metastases increased in size, 9 years after surgery, and she was treated with lapatinib and capecitabine. The efficacy of chemotherapy was judged as a partial response. The second patient was a 74-year-old woman who was diagnosed with invasive ductal carcinoma in 2005. The tumor was ER-negative, PgR-positive, and HER2-positive; she was treated with trastuzumab and paclitaxel. She developed dyspnea in January 2010. Chest radiograph showed increased lung metastases and left pleural effusion; she was treated with lapatinib and capecitabine. Lung metastases decreased and left pleural effusion disappeared after the first cycle of chemotherapy. The efficacy of chemotherapy was judged as a partial response.}, } @article {pmid21076884, year = {2011}, author = {Fornasa, F and Pinali, L and Gasparini, A and Toniolli, E and Montemezzi, S}, title = {Diffusion-weighted magnetic resonance imaging in focal breast lesions: analysis of 78 cases with pathological correlation.}, journal = {La Radiologia medica}, volume = {116}, number = {2}, pages = {264-275}, pmid = {21076884}, issn = {1826-6983}, mesh = {Adolescent ; Adult ; Aged ; Biopsy ; Breast Diseases/*diagnosis/pathology ; Breast Neoplasms/diagnosis/pathology ; Contrast Media ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Meglumine ; Middle Aged ; Organometallic Compounds ; Predictive Value of Tests ; Sensitivity and Specificity ; Statistics, Nonparametric ; }, abstract = {PURPOSE: This study assessed the usefulness of magnetic resonance diffusion-weighted imaging (DWI) in distinguishing between benign and malignant breast lesions.

MATERIALS AND METHODS: Gadolinium-enhanced magnetic resonance imaging (MRI) and DWI with determination of the apparent diffusion coefficient (ADC) were performed on 78 women, each with a focal breast lesion at least 7 mm in diameter, which was studied by cytology or histology.

RESULTS: Final diagnoses were obtained by cytology in 29 cases and histology in 49 (11 percutaneous biopsies and 38 surgical specimens). There were 43 benign lesions (13 fibrocystic disease, eight fibroadenoma, seven adenosis, five normal breast tissue, four inflammatory lesions, three intramammary lymph nodes, two scleroelastosis and one fat necrosis) and 35 malignant lesions (30 invasive ductal carcinoma, two invasive lobular carcinoma, one ductal carcinoma in situ, one carcinomatous mastitis and one metastasis from neuroendocrine carcinoma). The mean ADC values were 1.677±0.151 for benign lesions and 1.298±0.129 for malignant lesions (p<0.001). With an ADC cutoff value of 1.48, DWI had 88.6% sensitivity [confidence interval (CI) 78.1%-99.1%] and 95.3% specificity (CI 88.9%-100%), with 31 true positives, four false negatives (three invasive ductal carcinoma and one carcinomatous mastitis), 41 true negatives and two false positives (one fat necrosis and one fibroadenoma). With the cutoff value set at 1.52, DWI sensitivity (35 true positive, no false negative) was 100% and specificity was 86% (CI 75.7%-96.3%) due to 37 true negatives and six false positives (an additional two fibroadenoma and two fibrocystic disease compared with those recorded with the cutoff set at 1.48). The overall accuracy of DWI considering both cutoff values (72 correct evaluations out of 78 cases) was 92.3% (CI 86.4%-98.2%).

CONCLUSIONS: DWI is a reliable tool for characterising focal breast lesions.}, } @article {pmid21076596, year = {2010}, author = {Choi, N and Ko, ES}, title = {Invasive ductal carcinoma in a mammary hamartoma: case report and review of the literature.}, journal = {Korean journal of radiology}, volume = {11}, number = {6}, pages = {687-691}, pmid = {21076596}, issn = {2005-8330}, mesh = {Aged ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Diagnosis, Differential ; Female ; Hamartoma/*diagnosis/surgery ; Humans ; Magnetic Resonance Imaging ; Mammography ; Mastectomy, Modified Radical ; Neoplasm Invasiveness ; Ultrasonography, Mammary ; }, abstract = {Mammary hamartomas are typically a benign condition and rarely develop into malignant lesions. Only 14 cases of carcinomas associated with a hamartoma have been documented in the literature. In this case report, we describe a case of invasive ductal carcinoma within a hamartoma in a 72-year-old woman. Mammography, ultrasonography, and magnetic resonance imaging showed the features of a typical hamartoma with a suspicious mass arising in it. This case illustrates the importance of identification of unusual findings in a typical mammary hamartoma on radiologic examinations.}, } @article {pmid21073252, year = {2010}, author = {Morrone, A and Dassoni, F and Pajno, MC and Marrone, R and Calcaterra, R and Franco, G and Maiani, E}, title = {Ulcers of the face and neck in a woman with pulmonary tuberculosis: presentation of a clinical case.}, journal = {Rural and remote health}, volume = {10}, number = {4}, pages = {1485}, pmid = {21073252}, issn = {1445-6354}, mesh = {Aged ; Antitubercular Agents/therapeutic use ; Ethiopia ; Female ; Humans ; Neck/*microbiology ; Rural Health Services ; Skin Ulcer/*microbiology ; Tuberculosis, Cutaneous/*diagnosis/drug therapy ; Tuberculosis, Pulmonary ; }, abstract = {INTRODUCTION: Tuberculosis (TB), which is endemic in developing countries, is an important public health problem. Cutaneous TB (CT) represents 1.5% of all TB cases and is considered to be a re-emerging pathology in developing countries due to co-infections with HIV, multidrug-resistant TB, a shortage of health facilities with appropriate diagnostic equipment, reduced access to treatment, and poor treatment compliance among patients who often resort to traditional medicine.

CASE REPORT: This report describes the case of a 70 year-old woman who attended the outpatients department of the Italian Dermatological Centre (IDC) in Mekelle, the capital city of Tigray (Northern Ethiopia), complaining of the appearance of two ulcers on her face and neck. The patient had a history of pulmonary TB, with her initial systemic treatment ceased after 1 month. Cytological examination of a needle aspiration from the neck lesion showed a non-specific bacterial superinfection. No acid-fast bacilli were found on Ziehl-Nielsen staining. On the basis of clinical suspicion of CT, it was decided to avoid biopsy for histology and culture and to immediately start anti-tubercular treatment. A significant improvement of the cutaneous lesions was noted after approximately 40 days.

CONCLUSION: Currently, the diagnosis of CT is based on careful clinical and histopathological correlation. The standard diagnostic approach is to biopsy for Ziehl-Nielsen stain, culture and histology. However, in rural areas of DC where diagnostic methods may not be available and advanced stages of disease such as CT are likely to be encountered, after the use of the most effective diagnostic tests available, empirical treatment on the basis of medical history and physical examination is suggested. Appropriate training of healthcare workers and public health education programs encouraging early presentation and improved patient treatment compliance are additional important preventative strategies.}, } @article {pmid21072300, year = {2010}, author = {Elgaili, EM and Abuidris, DO and Rahman, M and Michalek, AM and Mohammed, SI}, title = {Breast cancer burden in central Sudan.}, journal = {International journal of women's health}, volume = {2}, number = {}, pages = {77-82}, pmid = {21072300}, issn = {1179-1411}, abstract = {Breast cancer is a worldwide disease resulting in many deaths. Although breast cancer incidence is lower in Sub-Saharan African countries than in developed countries, African women are more likely than women in the developed world to be diagnosed at later stages of the disease and, thus, are more likely to die from it. This is due to the lack of awareness by women, accessibility to screening methods, and availability of African-based research findings that would influence decision making at the governmental level. This descriptive study was undertaken to shed light on the type, stage and age distribution of breast cancer at diagnosis in women living in central Sudan encompassing al-Gezira, Blue Nile, White Nile, and Sennar States. Cases comprised 1255 women from central Sudan diagnosed with breast cancer and referred to and treated at Institute of Nuclear Medicine, Molecular Biology, and Oncology, from January 1999 to December 2006. Data revealed that 74% of the women were <50 years old or premenopausal. Invasive ductal carcinoma was the most common pathology (82%) and women presenting with stage III or higher tumors that had already metastasized, while ductal carcinoma in situ was the least prevalent (0.5%) finding. Estrogen and progesterone receptors expression were performed on a limited number of samples and the overwhelming majority of cases were observed to be negative for estrogen and progesterone receptors expression.}, } @article {pmid21069405, year = {2011}, author = {Gennai, S and François, P and Sellier, E and Vittoz, JP and Hincky-Vitrat, V and Pavese, P}, title = {Prospective study of telephone calls to a hotline for infectious disease consultation: analysis of 7,863 solicited consultations over a 1-year period.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {30}, number = {4}, pages = {509-514}, pmid = {21069405}, issn = {1435-4373}, mesh = {Anti-Infective Agents/*therapeutic use ; Cell Phone ; Communicable Diseases/diagnosis/*drug therapy ; Cross Infection/diagnosis/drug therapy ; Hospitals, Private/statistics & numerical data ; Hospitals, University ; Hotlines/*statistics & numerical data ; Humans ; Outpatient Clinics, Hospital/statistics & numerical data ; Physicians ; Prospective Studies ; Referral and Consultation/*statistics & numerical data ; Specialization ; *Telephone ; }, abstract = {To respond to the increasing requests of non-infectious disease physicians for access to infectious diseases expertise, a hotline was created in the infectious diseases consultation (IDC) unit of the Grenoble university-affiliated hospital (GUH). This study describes the patterns of solicited consultations provided by the hotline during a 1-year period. We conducted a prospective study of consecutive solicited IDCs requested by physicians in 2008. A total of 7,863 consultations were requested by physicians over 1 year; 4,407 (56.0%) by ambulatory physicians, 2,933 (37.3%) by GUH physicians, and 523 (6.7%) by physicians in public or private hospitals. The majority of consultations were requested via cell phone (58.7%). The main reasons for requesting a consultation were related to antimicrobial treatment for hospital-based physicians and prophylaxis for ambulatory physicians (p < 0.001). Recommendations to perform diagnostic or monitoring tests were less frequent in ambulatory medicine (16%) than in the GUH (59%) or other hospitals (63%, p < 0.001). The route of consultation for patients with nosocomial infections was more likely to be formal (p < 0.001). The activity of the IDC hotline attests to an important need for such expertise consultation, both in hospitals and in ambulatory medicine.}, } @article {pmid21060149, year = {2010}, author = {Ben-Batalla, I and Seoane, S and Garcia-Caballero, T and Gallego, R and Macia, M and Gonzalez, LO and Vizoso, F and Perez-Fernandez, R}, title = {Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.}, journal = {The Journal of clinical investigation}, volume = {120}, number = {12}, pages = {4289-4302}, pmid = {21060149}, issn = {1558-8238}, mesh = {Adenocarcinoma/genetics/metabolism/pathology/secondary ; Animals ; Apoptosis ; Base Sequence ; Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology/secondary ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Mice ; Mice, SCID ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Transplantation ; RNA, Small Interfering/genetics ; Transcription Factor Pit-1/antagonists & inhibitors/*genetics/*metabolism ; Transplantation, Heterologous ; Tumor Stem Cell Assay ; }, abstract = {The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target.}, } @article {pmid21059199, year = {2010}, author = {Heymann, S and Delaloge, S and Rahal, A and Caron, O and Frebourg, T and Barreau, L and Pachet, C and Mathieu, MC and Marsiglia, H and Bourgier, C}, title = {Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome.}, journal = {Radiation oncology (London, England)}, volume = {5}, number = {}, pages = {104}, pmid = {21059199}, issn = {1748-717X}, mesh = {Adult ; Breast Neoplasms/genetics/radiotherapy/surgery ; Cohort Studies ; Female ; Genes, p53 ; Humans ; Incidence ; Li-Fraumeni Syndrome/*complications/genetics ; Middle Aged ; Neoplasms, Radiation-Induced/*epidemiology ; Radiotherapy, Adjuvant/adverse effects ; Young Adult ; }, abstract = {BACKGROUND: There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.

METHODS: We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.

RESULTS: Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.

CONCLUSIONS: These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.}, } @article {pmid21057787, year = {2011}, author = {Groheux, D and Giacchetti, S and Moretti, JL and Porcher, R and Espié, M and Lehmann-Che, J and de Roquancourt, A and Hamy, AS and Cuvier, C and Vercellino, L and Hindié, E}, title = {Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {38}, number = {3}, pages = {426-435}, pmid = {21057787}, issn = {1619-7089}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biological Transport ; Breast Neoplasms/*diagnosis/diagnostic imaging/*metabolism/pathology ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Middle Aged ; Prognosis ; Radionuclide Imaging ; Tumor Burden ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {PURPOSE: The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on (18)F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2-T4) were included in order to minimize bias of partial volume effect.

METHODS: In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV(max)) were compared to tumour characteristics as assessed on core biopsy.

RESULTS: There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV(max) was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER- SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value.

CONCLUSION: Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.}, } @article {pmid21056685, year = {2011}, author = {Levy, CB and Stumbo, AC and Ano Bom, AP and Portari, EA and Cordeiro, Y and Silva, JL and De Moura-Gallo, CV}, title = {Co-localization of mutant p53 and amyloid-like protein aggregates in breast tumors.}, journal = {The international journal of biochemistry & cell biology}, volume = {43}, number = {1}, pages = {60-64}, doi = {10.1016/j.biocel.2010.10.017}, pmid = {21056685}, issn = {1878-5875}, mesh = {Adult ; *Amyloid/chemistry/metabolism/ultrastructure ; *Breast Neoplasms/genetics/pathology/ultrastructure ; DNA, Neoplasm/metabolism ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation, Neoplastic ; *Genes, p53 ; Genetic Association Studies ; Humans ; Molecular Sequence Data ; Mutation ; *Tumor Suppressor Protein p53/chemistry/genetics/metabolism/ultrastructure ; }, abstract = {P53 is one of the most important tumor suppressor proteins in human cancers. Mutations in the TP53 gene are common features of malignant tumors and normally correlate to a more aggressive disease. In breast cancer, these gene alterations are present in approximately 20% of cases and are characteristically of missense type. In the present work we describe TP53 mutations in breast cancer biopsies and investigate whether wild and mutant p53 participate in protein aggregates formation in these breast cancer cases. We analyzed 88 biopsies from patients residing in the metropolitan area of Rio de Janeiro, and performed TP53 mutation screening using direct sequencing of exons 5-10. Seventeen mutations were detected, 12 of them were of missense type, 2 nonsenses, 2 deletions and 1 insertion. The presence of TP53 mutation was highly statistically associated to tumor aggressiveness of IDC cases, indicated here by Elston Grade III (p<0.0001). Paraffin embedded breast cancer tissues were analyzed for the presence of p53 aggregates through immunofluorescence co-localization assay, using anti-aggregate primary antibody A11, and anti-p53. Our results show that mutant p53 co-localizes with amyloid-like protein aggregates, depending on mutation type, suggesting that mutant p53 may form aggregates in breast cancer cells, in vivo.}, } @article {pmid21054873, year = {2010}, author = {Kennedy, S and Geradts, J and Bydlon, T and Brown, JQ and Gallagher, J and Junker, M and Barry, W and Ramanujam, N and Wilke, L}, title = {Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast.}, journal = {Breast cancer research : BCR}, volume = {12}, number = {6}, pages = {R91}, pmid = {21054873}, issn = {1465-542X}, support = {1R41CA128160-01/CA/NCI NIH HHS/United States ; 1UL1 RR024128-01/RR/NCRR NIH HHS/United States ; }, mesh = {Breast/pathology ; Breast Neoplasms/*diagnosis/pathology ; Female ; Hemoglobins/analysis ; Humans ; Menopause ; Neoplasm Recurrence, Local/*diagnosis ; Neoplasm, Residual/*diagnosis/pathology ; Spectrum Analysis/*methods ; beta Carotene/analysis ; }, abstract = {INTRODUCTION: Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. This is further complicated by the heterogeneity as a function of menopausal status. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, we evaluate ex-vivo breast tissue and determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition.

METHODS: Diffuse reflectance spectra were measured from 595 normal and 38 malignant sites from the margins of 104 partial mastectomy patients. All statistical tests were performed using Wilcoxon Rank-Sum tests. Normal and malignant sites were compared before stratifying the data by tissue type and depth and computing statistical differences. The frequencies of the normal tissue types were separated by menopausal status and compared to the corresponding optical properties.

RESULTS: The mean reduced scattering coefficient, < μs' >, and concentration of total hemoglobin, [THb]), showed statistical differences between malignant (< μs' > : 8.96 cm⁻¹ ± 2.24(MAD), [THb]: 42.70 μM ± 29.31(MAD)) compared to normal sites (< μs' > : 7.29 cm⁻¹± 2.15(MAD), [THb]: 32.09 μM ± 16.73(MAD)) (P < 0.05). The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < μs' > and A showed increased [β-carotene] within normal tissues. Scattering differentiated between most malignant sites, DCIS (9.46 cm⁻¹ ± 1.06(MAD)) and IDC (8.00 cm⁻¹ ± 1.81(MAD)), versus A (6.50 cm⁻¹ ± 1.95(MAD)). [β-carotene] showed marginal differences between DCIS (19.00 μM ± 6.93(MAD), and FG (15.30 μM ± 5.64(MAD)). [THb] exhibited statistical differences between positive sites (92.57 μM ± 18.46(MAD)) and FG (34.12 μM ± 22.77MAD), FA (28.63 μM ± 14.19MAD), and A (30.36 μM ± 14.86(MAD)). The diagnostic ability of the optical parameters was affected by distance of tumor from the margin as well as menopausal status. Due to decreased fibrous content and increased adipose content, normal sites in post-menopausal patients exhibited lower < μs' >, but higher [β-carotene] than pre-menopausal patients.

CONCLUSIONS: The data indicate that the ability of an optical parameter to differentiate benign from malignant breast tissues may be dictated by patient demographics. Scattering differentiated between malignant and adipose sites and would be most effective in post-menopausal women. [β-carotene] or [THb] may be more applicable in pre-menopausal women to differentiate malignant from fibrous sites. Patient demographics are therefore an important component to incorporate into optical characterization of breast specimens.}, } @article {pmid21053536, year = {2010}, author = {Markidou, S and Karydas, I and Papadopoulos, S and Christodoulidou, I and Skarpidi, E and Maounis, N}, title = {Fine needle aspiration cytology in primary breast angiosarcoma: a case report.}, journal = {Acta cytologica}, volume = {54}, number = {5 Suppl}, pages = {764-770}, pmid = {21053536}, issn = {0001-5547}, mesh = {Biopsy, Fine-Needle ; Breast/*pathology/surgery ; Breast Neoplasms/diagnosis/*pathology/surgery ; Diagnosis, Differential ; Epithelial Cells/pathology ; Female ; Hemangiosarcoma/diagnosis/*pathology/surgery ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; }, abstract = {BACKGROUND: Angiosarcoma of the breast is an uncommon, aggressive, vascular tumor. The cytomorphologic features of angiosarcomas have rarely been reported.

CASE: The present study describes a case of breast angiosarcoma initially diagnosed by fine needle aspiration cytology. Angiosarcoma appeared in the left breast of a 58-year-old woman after 12 years of a mastectomy (without radiotherapy) of the contralateral breast for invasive ductal carcinoma. Fine needle aspiration cytology yielded very bloody material with moderate cellularity. Microscopically, two types of cells were observed: spindle cells and epithelial-like cells with nuclear atypia. The latter were arranged in tight clusters with papillary configuration. Both cell types exhibited immunoreactivity for endothelial markers. The diagnosis of angiosarcoma was confirmed by histopathology of the surgically excised tumor.

CONCLUSION: Angiosarcoma rarely occurs in the breast, and a definitive diagnosis is extremely difficult relying exclusively on cytologic features. Predominance of epithelioid cells may suggest an epithelial tumor, especially in patients with a history of breast carcinoma, whereas predominance of spindle cells can be misinterpreted as phyllodes tumor or another type of sarcoma. Cell block immunocytochemistry and tumor cell labeling with endothelial markers are necessary for accurate diagnosis.}, } @article {pmid21045391, year = {2010}, author = {Bhalla, A and Manjari, M and Kahlon, SK and Kumar, P and Kalra, N}, title = {Cytokeratin 5/6 expression in benign and malignant breast lesions.}, journal = {Indian journal of pathology & microbiology}, volume = {53}, number = {4}, pages = {676-680}, doi = {10.4103/0377-4929.72026}, pmid = {21045391}, issn = {0974-5130}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Basal Cell/diagnosis/*pathology ; Female ; *Gene Expression ; Humans ; Immunohistochemistry/methods ; Keratin-5/*biosynthesis ; Keratin-6/*biosynthesis ; Microscopy/methods ; Middle Aged ; Prognosis ; Severity of Illness Index ; Staining and Labeling/methods ; }, abstract = {BACKGROUND: Cytokeratin s (CK) are used for the fingerprinting of carcinomas in general. In breast tissue, the luminal epithelial cells express CK 8/18, CK 7 and CK 19, while basal/myoepithelial cells express CK 5/6, CK 14 and CK 17.

MATERIAL AND METHODS: Immunohistochemical staining for cytokeratin 5/6 was applied on cell block sections of 23 cases of benign and 25 cases of malignant breast lesions using avidin biotin peroxidase technique. The distribution and intensity of staining was recorded and graded semiquantitatively.

RESULT: All benign lesions showed positive immunoreaction, with the staining index varying from 6-9, except lactating adenoma. The malignant lesions comprised three cases of ductal carcinoma in situ (DCIS) and 22 cases of infiltrating ductal carcinoma, not otherwise specified, IDC (NOS). None of the DCIS cases showed a positive immunoreaction. Among the IDC (NOS) lesions, six cases of grade III breast carcinoma exhibited a positive immunohistochemical reaction, the staining index of which varied from 2-6. The staining reaction in the malignant lesions was only cytoplasmic and the intensity was significantly less than that of benign lesions.

CONCLUSION: CK 5/6 expression breast carcinoma implies a 'basal like' molecular phenotype and is associated with poor prognosis. This antibody is also used as a component of panels to differentiate benign and malignant breast lesions.}, } @article {pmid21042943, year = {2011}, author = {Yu, KD and Wu, LM and Liu, GY and Wu, J and Di, GH and Shen, ZZ and Shao, ZM}, title = {Different distribution of breast cancer subtypes in breast ductal carcinoma in situ (DCIS), DCIS with microinvasion, and DCIS with invasion component.}, journal = {Annals of surgical oncology}, volume = {18}, number = {5}, pages = {1342-1348}, doi = {10.1245/s10434-010-1407-3}, pmid = {21042943}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/mortality/*pathology ; Female ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Breast ductal carcinoma in situ with microinvasion (DCIS-Mi) is considered to be the interim stage in the progression from DCIS to invasive breast cancer (IDC). Cases that exceed DCIS-Mi but still do not fulfill the diagnostic criteria of IDC often are observed. We define those cases as DCIS with invasion component (DCIS-I), and attempt to study the differences of clinicopathological features and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and DCIS-I.

METHODS: In this retrospective study, 550 consecutive DCIS patients were recruited, 271 (49.3%) cases were diagnosed as pure-DCIS, 67 as DCIS-Mi, and 212 as DCIS-I. They were categorized into four groups: luminal-A (ER+ and/or PR+, HER2-), luminal-B (ER+ and/or PR+, HER2+), ERBB2+ (ER-, PR-, HER2+), and basal-like (ER-, PR-, HER2-).

RESULTS: DCIS-Mi and DCIS-I patients tended to have larger tumors with highly graded nuclear (P = 0.011 for size; P < 0.0001 for nuclear grade). The proportion of luminal-like tumors decreased, whereas ERBB2+ and basal-like tumors increased in DCIS-I/DCIS-Mi compared with pure-DCIS (P = 0.039). Although the HER2-positive tumors displayed a stable proportion among DCIS subgroups, the essences of them were varying. In pure-DCIS, luminal-B was the major subtype of HER2-positive tumors (luminal-B vs. ERBB2+, 19% vs. 14.6%), whereas in DCIS-I, the proportion of luminal-B decreased vastly (luminal-B vs. ERBB2+, 12.8% vs. 23.5%). DCIS-I had a worse relapse-free survival outcome compared with pure-DCIS.

CONCLUSIONS: Different distribution of subtypes and distinctive characteristics among DCIS, DCIS-Mi, and DCIS-I indicate that they are distinct entities. Further studies with larger sample size are needed to replicate our observations.}, } @article {pmid21039041, year = {2010}, author = {Looi, LM and Cheah, PL and Ng, MH and Yip, CH and Mun, KS and Rahman, NA}, title = {Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {11}, number = {3}, pages = {713-716}, pmid = {21039041}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood ; Breast/metabolism/*pathology ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroadenoma/genetics/metabolism/*pathology ; Humans ; Middle Aged ; Polymerase Chain Reaction ; Prognosis ; Telomerase/*metabolism ; Telomere/*genetics ; }, abstract = {A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.}, } @article {pmid21036723, year = {2010}, author = {Al-Khattabi, H and Kelany, A and Buhmeida, A and Al-Maghrabi, J and Lari, S and Chaudhary, A and Gari, M and Abuzenadah, A and Al-Qahtani, M}, title = {Evaluation of HER-2/neu gene amplification by fluorescence in situ hybridization and immunohistochemistry in saudi female breast cancer.}, journal = {Anticancer research}, volume = {30}, number = {10}, pages = {4081-4088}, pmid = {21036723}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*enzymology/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Receptor, ErbB-2/biosynthesis/*genetics ; Saudi Arabia ; Young Adult ; }, abstract = {BACKGROUND: Amplification of the HER-2/neu oncogene and concomitant over-expression of its protein are detected in approximately 18% of invasive ductal carcinoma of the breast and is associated with poor prognosis. This study tested the use of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to evaluate the HER-2/neu gene status and to ascertain the concordance rate between the two methods.

PATIENTS AND METHODS: Eighty two tumour samples containing representative tumour were divided for testing using each assay. HER-2/neu gene amplification is scored as a ratio of HER-2/neu gene amplification to chromosome 17. The ratio should be >2.2 to be considered as positive. 20 cells should be counted and an average score taken. An extra 20 cells should be counted if the ratio is between 1.8-2.2.

RESULTS: Seventy five effective samples were used. HER-2/neu gene was amplified in 19 out of 75 cases (25%) whereas, HER-2 protein, by IHC was over-expressed in 18 out of 75 cases (24%). In the 44 negative cases by IHC analysis only 7 cases (16%) of them showed amplification by FISH. Three out of 13 cases (23 %) scored as +2 showed gene amplification by FISH while 9 cases out of 18 cases (50%) were scored as +3. High concordance with FISH results 37:44 (84 %) was noted in negative cases (0/+1 cases), while lower concordance 3:13 (23 %) was seen in +2 cases.

CONCLUSION: This study revealed a significant concordance between FISH results and IHC results. The study also showed that HER2/neu amplification is higher in Saudi patients than other western populations. However, due to the inherent failures of the IHC assay, FISH should always be used when the IHC results are inconclusive. The rational algorithm for HER-2/neu testing would be to perform IHC first, followed by FISH to validate equivocal IHC results.}, } @article {pmid21033319, year = {2010}, author = {Olu-Eddo, AN and Momoh, MI}, title = {Clinicopathological study of male breast cancer in Nigerians and a review of the literature.}, journal = {Nigerian quarterly journal of hospital medicine}, volume = {20}, number = {3}, pages = {121-124}, pmid = {21033319}, issn = {0189-2657}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy ; Black People/statistics & numerical data ; Breast Neoplasms, Male/epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/*pathology/therapy ; Hospitals, Teaching ; Humans ; Male ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Nigeria/epidemiology ; Prevalence ; Retrospective Studies ; Tamoxifen/therapeutic use ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is rare in men, accounting for approximately 1% of all cases of breast carcinoma.

OBJECTIVE: To evaluate the incidence, presentation, histopathological types, management and outcome of male patients with breast cancer treated at the University of Benin Teaching Hospital, Benin City, Nigeria.

METHODS: A 20 year (1987-2006) retrospective study of all male patients with breast cancer was done. Clinic demographic data regarding age, sex, clinical information, treatment and follow up were obtained from request cards and case files. Slides were retrieved from the archives of the Department of Pathology and reviewed.

RESULTS: Sixteen cases of male breast cancer were encountered. This comprised 18.4% of the breast lesions in males and 2.8% of all breast cancers seen in the Department during the 20 year study period. The ages of patients ranged from 35-90 years with a mean age of 64.4 years. Delay in patient presentation to physician ranged from 14-49 months. Clinically, patients presented mostly with a self-detected lump (87.5%), or ulceration (68.8%), nipple discharge (43.8%) and nipple bleeding (25.0%). Unilaterality was observed in 87.5% of cases were while 12.5% of cases were bilateral (metachronous). Invasive ductal carcinoma (81.25%) was the predominant histological type of cancer. Stage IV disease was most commonly encountered (43.8%). Eleven (68.8%) patients had modified radical mastectomy. Only 31.3% patients came for follow-up, for a median duration of 10 months.

CONCLUSION: Male breast cancer is rare and patients present late with advanced disease. Education needs to be intensified to increase awareness of the disease.}, } @article {pmid21029700, year = {2010}, author = {Wang, XH and Peng, WJ and Xin, C and Tan, HN and Gu, YJ and Tang, F and Mao, J}, title = {[Value of dynamic contrast-enhanced MRI in assessment of early response to neoadjuvant chemotherapy in breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {32}, number = {7}, pages = {539-543}, pmid = {21029700}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carboplatin/administration & dosage ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Staging ; Neoplasm, Residual ; Paclitaxel/administration & dosage ; }, abstract = {OBJECTIVE: To assess the value of dynamic contrast-enhanced MRI (DMRI) in predicting early response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) and to assess the accuracy of MRI in evaluation of residual disease after NAC.

METHODS: Forty-three women with LABC (44 lesions, all were invasive ductal carcinoma) underwent DMRI before, after the first and final cycles of NAC. For each patient, the tumor volume, early enhancement ratio (E1), maximum enhancement ratio (Emax), and maximum enhancement time (Tmax), dynamic signal intensity-time curve were obtained during treatment. The residual tumor volumes obtained by DMRI were compared with pathological findings to assess the accuracy of DMRI.

RESULTS: After the first cycle of NAC, the mean volume of responders decreased insignificantly (P = 0.055), but after NAC, mean volume of residual tumor decreased significantly (P = 0.000). Morphological changes: 29 cases showed a concentric shrinkage pattern while 7 cases showed a dendritic shrinkage pattern. Significant differences were found in E1, Emax and Tmax between responders and non-responders (P < 0.05). After the first cycle of NAC, E1, Emax and Tmax of responders changed significantly (P < 0.001), while there was no significant change in non-responders (P > 0.05). After NAC, the dynamic signal intensity-time types were changed in responders, and tended to be significantly flattening, while no significant change was found in non-responders. The residual tumor volume correlation coefficient between MRI and pathology measurements was very high (r = 0.866, P < 0.01).

CONCLUSION: DMRI is useful to evaluate the early response to NAC in LABC. The presence and volume of residual tumor in LABC patients treated with NAC can be accurately evaluated by DMRI.}, } @article {pmid20979875, year = {2010}, author = {Ying, JM and Guo, L and Liu, XY and Qiu, T and Lü, N}, title = {[Automated silver-enhanced in situ hybridization detection assay for human epidermal growth factor receptor 2 gene status determination in breast cancer].}, journal = {Zhonghua yi xue za zhi}, volume = {90}, number = {24}, pages = {1674-1677}, pmid = {20979875}, issn = {0376-2491}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Humans ; In Situ Hybridization/*methods ; Middle Aged ; Prospective Studies ; Receptor, ErbB-2/*genetics ; Silver Compounds ; }, abstract = {OBJECTIVE: To evaluate the concordance of human epidermal growth factor receptor 2 (HER2) gene amplification in invasive breast cancer by the techniques of fluorescence in situ hybridization (FISH) and silver-enhanced in situ hybridization (SISH).

METHODS: A prospective study of 63 invasive breast cancer specimens excised between May 2009 and November 2009 was conducted by automated immunohistochemistry (IHC) staining and bright field automated SISH. HER2 gene status was also examined by FISH in 43 cases. An evaluation was performed according to the ASCO/CAP guidelines (2007).

RESULTS: Among 63 breast invasive ductal carcinoma tested by automated SISH, 61 cases were successfully evaluated. Gene amplification was detected in 97% (29/30) HER2 protein expression positive (3+) cases and in 18% (2/11) equivocal (2+) cases. Two of 11 (18%) HER2 expression 2+ cases were equivocal for gene amplification. In 43 cases examined by FISH, HER2 gene amplification was detected in 95% (20/21) HER2 expression positive (3+) cases and in one equivocal (2+) cases. Three of 10 (30%) expression 2+ cases were equivocal for gene amplification. No gene amplification was detected in expression negative (1 +/0) cases by either SISH or FISH (0/20 and 0/12 respectively). The results of SISH and FISH were identical in 42 cases examined by the above two techniques, including 21 HER2 gene amplification positive, 2 equivocal and 19 negative cases. One case was FISH equivocal and SISH negative. And the overall concordance between FISH and SISH was 98%.

CONCLUSIONS: There is high concordance rate between SISH and FISH results for assessing the HER2 gene amplification status of excised breast cancer specimens. However, SISH has more advantages and it is particularly suited for routine application in surgical pathology.}, } @article {pmid20978320, year = {2010}, author = {Moelans, CB and de Weger, RA and Monsuur, HN and Maes, AH and van Diest, PJ}, title = {Molecular differences between ductal carcinoma in situ and adjacent invasive breast carcinoma: a multiplex ligation-dependent probe amplification study.}, journal = {Analytical cellular pathology (Amsterdam)}, volume = {33}, number = {3}, pages = {165-173}, doi = {10.3233/ACP-CLO-2010-0546}, pmid = {20978320}, issn = {2210-7185}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal/*metabolism ; Female ; Humans ; Microdissection ; *Nucleic Acid Amplification Techniques ; }, abstract = {Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown. In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.There were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p=0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high-grade IDC was similar, and although EGFR alterations were exclusively found in high-grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.In conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high-grade DCIS showed more copy number changes than low/intermediate-grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high-grade DCIS specific genes may be potential targets for treatment and/or predict progression.}, } @article {pmid20977976, year = {2010}, author = {Li, W and Liu, F and Lei, T and Xu, X and Liu, B and Cui, L and Wei, J and Guo, X and Lang, R and Fan, Y and Gu, F and Tang, P and Zhang, X and Fu, L}, title = {The clinicopathological significance of CD44+/CD24-/low and CD24+ tumor cells in invasive micropapillary carcinoma of the breast.}, journal = {Pathology, research and practice}, volume = {206}, number = {12}, pages = {828-834}, doi = {10.1016/j.prp.2010.09.008}, pmid = {20977976}, issn = {1618-0631}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply/metabolism/*pathology ; CD24 Antigen/*metabolism ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/blood supply/metabolism/*pathology ; Carcinoma, Papillary/blood supply/metabolism/*pathology ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Risk ; Vimentin/metabolism ; }, abstract = {Breast cancer cells with a CD44(+)/CD24(-/low) phenotype have been suggested to have tumor-initiating properties. It is unclear whether their presence correlates with clinicopathological features of invasive micropapillary carcinoma (IMPC) of the breast, an unusual subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. CD44 and CD24 expression was determined by double-staining immunohistochemistry in 103 cases of IMPC and in 94 cases of invasive ductal carcinoma (IDC). The prevalence of CD44(+)/CD24(-/low) tumor cells was higher in IMPC than in invasive ductal carcinoma IDC (P=0.018). The CD44(+)/CD24(-/low) tumor cells were also detected in adjacent stroma surrounding the micropapillary structure in 53.4% (55/103) of IMPC, but only in 7.4% (7/94) of stroma of IDC. These tumor cells in stroma of IMPC were positive for vimentin and α-smooth muscle actin, and negative for E-cadherin. The CD44(+)/CD24(-/low) tumor cells in the micropapillary structure of IMPC were associated with those in stroma (P=0.000). Moreover, they were both associated with lymphovascular invasion and extranodal extension, respectively (P<0.05). The proportion of CD24(+) tumor cells was also higher in IMPC than in IDC (P=0.035), and the CD24(+) tumor cells were associated with lymph node metastasis in IMPC (P=0.010). The results suggest that the increased proportion of CD44(+)/CD24(-/low) tumor cells and CD24(+) tumor cells and the epithelial mesenchymal transition may play an important role in aggressiveness and high metastatic risk of breast IMPC.}, } @article {pmid20977948, year = {2011}, author = {Kou, PM and Schwartz, Z and Boyan, BD and Babensee, JE}, title = {Dendritic cell responses to surface properties of clinical titanium surfaces.}, journal = {Acta biomaterialia}, volume = {7}, number = {3}, pages = {1354-1363}, pmid = {20977948}, issn = {1878-7568}, support = {AR052102/AR/NIAMS NIH HHS/United States ; R01 EB004633/EB/NIBIB NIH HHS/United States ; R01 AR052102/AR/NIAMS NIH HHS/United States ; R01 AR052102-04/AR/NIAMS NIH HHS/United States ; R01 EB004633-04/EB/NIBIB NIH HHS/United States ; EB004633/EB/NIBIB NIH HHS/United States ; }, mesh = {Cell Differentiation ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Humans ; Microscopy, Electron, Scanning ; Osteoblasts/cytology/metabolism/ultrastructure ; Principal Component Analysis ; Surface Properties ; Titanium/*chemistry ; }, abstract = {Dendritic cells (DCs) play pivotal roles in responding to foreign entities during the innate immune response and in initiating effective adaptive immunity as well as maintaining immune tolerance. The sensitivity of DCs to foreign stimuli also makes them useful cells to assess the inflammatory response to biomaterials. Elucidating material property-DC phenotype relationships using a well-defined biomaterial system is expected to provide criteria for immunomodulatory biomaterial design. Clinical titanium (Ti) substrates, including pretreatment (PT), sand blasted and acid etched (SLA), and modified SLA (modSLA), with different roughnesses and surface energies were used to treat DCs and resulted in differential DC responses. PT and SLA induced a mature DC (mDC) phenotype, while modSLA promoted a non-inflammatory environment by supporting an immature DC (iDC) phenotype, based on surface marker expression, cytokine production profiles and cell morphology. Principal component analysis (PCA) confirmed these experimental results, and also indicated that the non-stimulating property of modSLA covaried with certain surface properties, such as high surface hydrophilicity, percent oxygen and percent Ti of the substrates. In addition to previous research that demonstrated superior osteogenic properties of modSLA compared with PT and SLA, the results reported herein indicates that modSLA may further benefit implant osteointegration by reducing local inflammation and its associated osteoclastogenesis.}, } @article {pmid20976182, year = {2010}, author = {Beraki, E and Sauer, T}, title = {Determination of HER-2 status on FNAC material from breast carcinomas using in situ hybridization with dual chromogen visualization with silver enhancement (dual SISH).}, journal = {CytoJournal}, volume = {7}, number = {}, pages = {21}, pmid = {20976182}, issn = {1742-6413}, abstract = {During the last years, HER-2 status kits and protocols for chromogen visualization of hybridization signals have come on the market. The first generation using chromogen visualization used single color probes. The second generation, now emerging on the market, uses dual chromogen visualization. The aim of this study has been to test a new dual color chromogen kit (Ventana INFORM HER2 Dual Colour ISH Roche(®)) and compare the results with our in-house method(s). The material consisted primarily of cytological material from invasive breast carcinomas in 49 women. Dual SISH was done on all 49 cytological and histological specimens. The histological specimens were treated according to the manufacturer's recommendations. The procedure was modified in several steps in order to adapt it to the cytological material. Hybridization failed in two cytological specimens. Dual SISH showed concordant results on cytological and histological material as to amplified/not amplified. The included cases had the same HER-2 expression in the invasive and the in situ components on histology. Four IDC showed HER-2 amplification (8.5%). Polysomy was found in two cases. All dual SISH results except for one concurred with the results of the in-house method(s) (1/47=2.1%). The dual SISH is suitable for cytological examination of HER-2 status. The protocol must be optimized for cytological material.}, } @article {pmid20968230, year = {2010}, author = {Christen, AG and Christen, JA}, title = {Mosquitoes, flies and dental cavities: Dr. Howard Riley Raper's public campaign to prevent toothache.}, journal = {Journal of the history of dentistry}, volume = {58}, number = {2}, pages = {87-90}, pmid = {20968230}, issn = {1089-6287}, mesh = {Dental Caries/*history ; History, 19th Century ; History, 20th Century ; Humans ; Public Health Dentistry/*history ; Radiography, Dental/history ; Toothache/*history ; United States ; }, abstract = {Dr. Howard Riley Raper (1886-1978) was an early oral health pioneer and dental roentgenology faculty member of the Indiana Dental College (IDC) who single-handedly introduced key concepts in radiology to dentistry. Due to his efforts, IDC became in 1910-11 the first dental school to have a regular course in dental radiology. Virtually all American dental schools soon added this subject to their regular curriculum. Raper's text, Elementary and Dental Radiography (1913) became the first comprehensive student textbook of dental X-ray diagnosis. In his 1933 Blue Book entitled, The New Aim in the Care of the Teeth, Raper elaborated upon his mission to prevent caries, by comparing the insidious damages of tooth decay with the threat of insect-borne disease.}, } @article {pmid20963473, year = {2011}, author = {Szasz, AM and Tokes, AM and Micsinai, M and Krenacs, T and Jakab, C and Lukacs, L and Nemeth, Z and Baranyai, Z and Dede, K and Madaras, L and Kulka, J}, title = {Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis.}, journal = {Clinical & experimental metastasis}, volume = {28}, number = {1}, pages = {55-63}, pmid = {20963473}, issn = {1573-7276}, mesh = {Breast Neoplasms/*diagnosis/*metabolism/pathology ; Claudins/*biosynthesis/metabolism ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*diagnosis/genetics ; Middle Aged ; Prognosis ; Tissue Array Analysis ; }, abstract = {Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.}, } @article {pmid20956025, year = {2011}, author = {Odumosu, O and Payne, K and Baez, I and Jutzy, J and Wall, N and Langridge, W}, title = {Suppression of dendritic cell activation by diabetes autoantigens linked to the cholera toxin B subunit.}, journal = {Immunobiology}, volume = {216}, number = {4}, pages = {447-456}, pmid = {20956025}, issn = {1878-3279}, support = {R21 DK057206-02/DK/NIDDK NIH HHS/United States ; R21 DK063576/DK/NIDDK NIH HHS/United States ; R21 DK-99-013/DK/NIDDK NIH HHS/United States ; }, mesh = {Autoantigens/genetics/immunology/*pharmacology ; Cells, Cultured ; Cholera Toxin/genetics/immunology/*pharmacology ; Dendritic Cells/*drug effects/immunology ; Gene Order ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/*pharmacology ; Interleukin-10/metabolism ; Proinsulin/genetics/immunology/*pharmacology ; Recombinant Fusion Proteins/genetics/immunology/metabolism/*pharmacology ; Toll-Like Receptor 2/metabolism ; Up-Regulation/*drug effects ; }, abstract = {Antigen presenting cells, specifically dendritic cells (DCs) are a focal point in the delicate balance between T cell tolerance and immune responses contributing to the onset of type I diabetes (T1D). Weak adjuvant proteins like the cholera toxin B subunit when linked to autoantigens may sufficiently alter the balance of this initial immune response to suppress the development of autoimmunity. To assess adjuvant enhancement of autoantigen mediated immune suppression of Type 1 diabetes, we examined the cholera toxin B subunit (CTB)-proinsulin fusion protein (CTB-INS) activation of immature dendritic cells (iDC) at the earliest detectable stage of the human immune response. In this study, Incubation of human umbilical cord blood monocyte-derived immature DCs with CTB-INS autoantigen fusion protein increased the surface membrane expression of DC Toll-like receptor (TLR-2) while no significant upregulation in TLR-4 expression was detected. Inoculation of iDCs with CTB stimulated the biosynthesis of both CD86 and CD83 co-stimulatory factors demonstrating an immunostimulatory role for CTB in both DC activation and maturation. In contrast, incubation of iDCs with proinsulin partially suppressed CD86 co-stimulatory factor mediated DC activation, while incubation of iDCs with CTB-INS fusion protein completely suppressed iDC biosynthesis of both CD86 and CD83 costimulatory factors. The incubation of iDCs with increasing amounts of insulin did not increase the level of immune suppression but rather activated DC maturation by stimulating increased biosynthesis of both CD86 and CD83 costimulatory factors. Inoculation of iDCs with CTB-INS fusion protein dramatically increased secretion of the immunosuppressive cytokine IL-10 and suppressed synthesis of the pro-inflammatory cytokine IL12/23 p40 subunit protein suggesting that linkage of CTB to insulin (INS) may play an important role in mediating DC guidance of cognate naïve Th0 cell development into immunosuppressive T lymphocytes. Taken together, the experimental data suggests Toll like receptor 2 (TLR-2) plays a dominant role in CTB mediated INS inhibition of DC induced type 1 diabetes onset in human Type 1 diabetes autoimmunity. Further, fusion of CTB to the autoantigen was found to be essential for enhancement of immune suppression as co-delivery of CTB and insulin did not significantly inhibit DC costimulatory factor biosynthesis. The experimental data presented supports the hypotheses that adjuvant enhancement of autoantigen mediated suppression of islet beta cell inflammation is dependent on CTB stimulation of dendritic cell TLR2 receptor activation and co-processing of both CTB and the autoantigen in the same dendritic cell.}, } @article {pmid20955380, year = {2010}, author = {Subramaniam, MM and Chan, JY and Omar, MF and Ito, K and Ito, Y and Yeoh, KG and Salto-Tellez, M and Putti, TC}, title = {Lack of RUNX3 inactivation in columnar cell lesions of breast.}, journal = {Histopathology}, volume = {57}, number = {4}, pages = {555-563}, doi = {10.1111/j.1365-2559.2010.03675.x}, pmid = {20955380}, issn = {1365-2559}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; DNA Methylation ; Female ; Humans ; Immunohistochemistry ; Promoter Regions, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {AIMS: Ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) exhibit frequent RUNX3 inactivation by promoter hypermethylation and protein mislocalization. The aim of this study was to analyse columnar cell lesions (CCLs) to further characterize RUNX3 involvement in breast carcinogenesis.

METHODS AND RESULTS:   RUNX3 expression and methylation was analysed by immunohistochemistry and methylation-specific polymerase chain reaction (PCR), respectively, in 75 CCLs. Our previously reported DCIS and IDC data were also included. Consistent with terminal duct lobular units (TDLUs) (73 of 75, 97%), active nuclear RUNX3 protein was observed in 73 of 75 (97%) CCLs [columnar cell change, 46 of 48 (96%); columnar cell hyperplasia, 12 of 12 (100%) and flat epithelial atypia, 15 of 15 (100%). In contrast to matched TDLUs from cancer specimens [four of 40 (10%)] and CCLs, significantly inactivated RUNX3 expression was detected in DCIS [17 of 20 (85%)] and IDC [18 of 20 (90%)] (all P < 0.001). RUNX3 methylation was more frequent in DCIS [15 of 20 (75%)] and IDC [16 of 20 (80%)] than CCLs [(none of 20 (0%)] and matched TDLUs [one of 10 (10%)] from cancer patients (all P < 0.001).

CONCLUSIONS:   RUNX3 inactivation occurs specifically in DCIS and IDC cells. In addition, RUNX3 inactivation may not be a common association between CCLs and breast carcinomas.}, } @article {pmid20953905, year = {2011}, author = {Fu, Z and Jiao, M and Zhang, M and Xu, F and Yuan, W and Pang, D and Li, D}, title = {LFA-1 gene polymorphisms are associated with the sporadic infiltrative duct breast carcinoma in Chinese Han women of Heilongjiang Province.}, journal = {Breast cancer research and treatment}, volume = {127}, number = {1}, pages = {265-271}, doi = {10.1007/s10549-010-1203-6}, pmid = {20953905}, issn = {1573-7217}, mesh = {Adult ; Aged ; Alleles ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; China ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphocyte Function-Associated Antigen-1/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {The infiltrative duct carcinoma (IDC) is the most common malignant breast cancer in females and genetic factors appear to play a significant role in the susceptibility of IDC. The LFA-1 is a crucial co-stimulatory molecule in immune system and may affect the development of breast IDC. In order to clarify the association of LFA-1 polymorphisms with IDC, a case-control study was conducted in women from Heilongjiang Province, Northeast of China. We scrutinized four genetic polymorphisms in LFA-1 gene, which may influence the activity and function of LFA-1. Our research subjects consist of 537 cases with IDC and 577 age-matched healthy controls. Genotypes were determined by PCR-RFLP. Data were analyzed using the χ(2) test by SPSS 13.0 and Haploview 4.1 softwares. The association between LFA-1 polymorphisms and the clinical features of IDC was analyzed. In rs2230433, the frequency of GG genotype and G allele was lower in cases than in controls (P = 0.0316 and 0.0480). And rs2230433, CG genotype was higher in cases (P = 0.0397). In rs8058823, the frequency of AA genotype and A allele was lower in cases than in controls (P = 0.00000418 and 0.00000267). And rs8058823, AG genotype was higher in cases (P = 0.00000747). The frequency of haplotype CCGA was lower in patients. Significant association was shown between the four SNPs of LFA-1 gene and estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, and P53 statuses. In addition, no association was found between LFA-1 gene polymorphisms and tumor size, and neither was it between LFA-1 gene polymorphisms and lymph node metastasis. Our results primarily suggested that LFA-1 gene polymorphisms may predict the sporadic breast IDC risk and prognosis factors in Chinese Han women in Heilongjiang Province.}, } @article {pmid20953227, year = {2010}, author = {Sule, E and Akpo, E and Akhator, A and Obaseki, D}, title = {Axillary breast cancer in a Nigerian woman.}, journal = {The New Zealand medical journal}, volume = {123}, number = {1324}, pages = {84-87}, pmid = {20953227}, issn = {1175-8716}, mesh = {Adult ; *Axilla ; Breast Neoplasms/*diagnosis/drug therapy/radiotherapy ; Carcinoma, Ductal, Breast/*diagnosis/drug therapy/radiotherapy ; Choristoma/*diagnosis/drug therapy/radiotherapy ; Diagnosis, Differential ; Female ; Humans ; }, abstract = {Ectopic breast cancer is rare and diagnosis is commonly delayed. We report the case of a 34-year-old Nigerian woman with a locally advanced invasive ductal carcinoma in the axillary breast. She underwent an axillary mastectomy and is due to receive adjuvant chemotherapy and radiotherapy. The management of this patient is discussed in relation to existing medical literature on the subject.}, } @article {pmid20951508, year = {2012}, author = {Zauls, AJ and Watkins, JM and Wahlquist, AE and Brackett, NC and Aguero, EG and Baker, MK and Jenrette, JM and Garrett-Mayer, E and Harper, JL}, title = {Outcomes in women treated with MammoSite brachytherapy or whole breast irradiation stratified by ASTRO Accelerated Partial Breast Irradiation Consensus Statement Groups.}, journal = {International journal of radiation oncology, biology, physics}, volume = {82}, number = {1}, pages = {21-29}, doi = {10.1016/j.ijrobp.2010.08.034}, pmid = {20951508}, issn = {1879-355X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Analysis of Variance ; Axilla ; Brachytherapy/methods ; Breast Neoplasms/classification/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/classification/mortality/pathology/*radiotherapy/secondary ; Carcinoma, Intraductal, Noninfiltrating/classification/mortality/pathology/*radiotherapy/secondary ; Chemotherapy, Adjuvant ; *Consensus ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Radiation Oncology ; Risk Assessment/methods ; Survival Analysis ; Time Factors ; Treatment Failure ; }, abstract = {PURPOSE: The American Society for Radiation Oncology published a Consensus Statement for accelerated partial breast irradiation identifying three groups: Suitable, Cautionary, and Unsuitable. The objective of this study was to compare oncologic outcomes in women treated with MammoSite brachytherapy (MB) vs. whole breast irradiation (WBI) after stratification into Statement groups.

METHODS: Eligible women had invasive carcinoma or ductal carcinoma in situ (DCIS) ≤ 3 cm, and ≤ 3 lymph nodes positive. Women were stratified by radiation modality and Statement groups. Survival analysis methods including Kaplan-Meier estimation, Cox regression, and competing risks analysis were used to assess overall survival (OS), disease-free survival (DFS), time to local failure (TTLF), and tumor bed failure (TBF).

RESULTS: A total of 459 (183 MB and 276 WBI) patients were treated from 2002 to 2009. After a median follow-up of 45 months, we found no statistical differences by stratification group or radiation modality with regard to OS and DFS. At 4 years TTLF or TBF were not statistically different between the cohorts. Univariate analysis in the MB cohort revealed that nodal positivity (pN1 vs. pN0) was related to TTLF (hazard ratio 6.39, p = 0.02). There was a suggestion that DCIS histology had an increased risk of failure when compared with invasive ductal carcinoma (hazard ratio 3.57, p = 0.06).

CONCLUSIONS: MB and WBI patients stratified by Statement groups seem to combine women who will have similar outcomes regardless of radiation modality. Although outcomes were similar, we remain guarded in overinterpretation of these preliminary results until further analysis and long-term follow-up data become available. Caution should be used in treating women with DCIS or pN1 disease with MB.}, } @article {pmid20947169, year = {2010}, author = {Simone, R and Barbarat, B and Rabellino, A and Icardi, G and Bagnasco, M and Pesce, G and Olive, D and Saverino, D}, title = {Ligation of the BT3 molecules, members of the B7 family, enhance the proinflammatory responses of human monocytes and monocyte-derived dendritic cells.}, journal = {Molecular immunology}, volume = {48}, number = {1-3}, pages = {109-118}, doi = {10.1016/j.molimm.2010.09.005}, pmid = {20947169}, issn = {1872-9142}, mesh = {Apoptosis ; B7-1 Antigen/*immunology ; Blotting, Western ; Cell Line ; Cell Separation ; Dendritic Cells/*immunology/metabolism ; Flow Cytometry ; Humans ; Immunoprecipitation ; Inflammation/*immunology ; Lymphocyte Activation/immunology ; Monocytes/*immunology/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*immunology ; }, abstract = {BT3 is a new family of immunoreceptors belonging to the extended B7 family. BT3 molecules are expressed on the surface of resting and activated monocytes and monocyte-derived dendritic cells (iDC). We show that BT3 cross-linking, in the absence of other survival factors, provides a survival signal for monocytes and iDC and induces up-regulation of costimulatory molecules, such as CD80 and CD86, and HLA-DR. We further analyzed the effects of BT3 cross-linking on various proinflammatory responses on monocytes and iDC. The results obtained showed that BT3 engagement is able to modulate the production of IL8/CXCL8, IL-1β and IL-12/p70. Moreover, we demonstrated a synergistic effect between BT3 and Toll-like receptors ligands on both monocytes and iDC in up-regulating the production of proinflammatory cytokines. Thus, BT3 could be involved in the regulation of the balance between immune activation and suppression. A better understanding of its physiological role of these families of receptors awaits the precise identification of the nature, origin, expression, and distribution of their ligands.}, } @article {pmid20946688, year = {2010}, author = {Kwon, JH and Kim, YJ and Lee, KW and Oh, DY and Park, SY and Kim, JH and Chie, EK and Kim, SW and Im, SA and Kim, IA and Kim, TY and Park, IA and Noh, DY and Bang, YJ and Ha, SW}, title = {Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {557}, pmid = {20946688}, issn = {1471-2407}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/biosynthesis ; *Lymphatic Metastasis ; Middle Aged ; Prospective Studies ; Recurrence ; Registries ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Whether a systemic adjuvant treatment is needed is an area of controversy in patients with node-negative early breast cancer with tumor size of ≤1 cm, including T1mic.

METHODS: We performed a retrospective analysis of clinical and pathology data of all consecutive patients with node-negative T1mic, T1a, and T1b invasive ductal carcinoma who received surgery between Jan 2000 and Dec 2006. The recurrence free survival (RFS) and risk factors for recurrence were identified.

RESULTS: Out of 3889 patients diagnosed with breast cancer, 375 patients were enrolled (T1mic:120, T1a:93, T1b:162). Median age at diagnosis was 49. After a median follow up of 60.8 months, 12 patients developed recurrences (T1mic:4 (3.3%), T1a:2 (2.2%), T1b:6 (3.7%)), with a five-year cumulative RFS rate of 97.2%. Distant recurrence was identified in three patients. Age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) and triple negative disease (HR 4.93; 95% CI 1.312-18.519, p = 0.018) were significantly associated with a higher rate of recurrence. HER2 overexpression, Ki-67, and p53 status did not affect RFS.

CONCLUSIONS: Prognosis of node-negative breast cancer with T1mic, T1a and T1b is excellent, but patients under 35 years of age or with triple negative disease have a relatively high risk of recurrence.}, } @article {pmid20945328, year = {2010}, author = {Jacquet, SF and Balleyguier, C and Garbay, JR and Bourgier, C and Mathieu, MC and Delaloge, S and Vielh, P}, title = {Fine-needle aspiration cytopathology--an accurate diagnostic modality in mammary carcinoma with osteoclast-like giant cells: a study of 8 consecutive cases.}, journal = {Cancer cytopathology}, volume = {118}, number = {6}, pages = {468-473}, doi = {10.1002/cncy.20112}, pmid = {20945328}, issn = {1934-662X}, mesh = {Adult ; Biopsy, Fine-Needle/*methods ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Female ; Giant Cells/*pathology ; Humans ; Middle Aged ; Osteoclasts/*pathology ; }, abstract = {BACKGROUND: Invasive ductal carcinoma with osteoclast-like giant cells (OGCs) is a very rare breast tumor the main characteristic of which is the presence of multinucleated cells of histiocytic nature.

METHODS: The authors report a study of 8 consecutive cases of fine-needle aspiration cytopathology (FNAC) of breast nodules in which OGCs and malignant epithelial cells were associated and diagnosed as mammary carcinoma with OGCs. These cases were selected over a period of 5 years from more than 6000 patients who were examined during a weekly, single-day, multidisciplinary breast clinic. The corresponding biopsies and surgical specimens were examined histologically in an immunohistochemical study using a histiocytic marker (cluster of differentiation 68 [CD68]).

RESULTS: Conventional histologic analysis made it possible to diagnose 5 of the 8 cases as mammary carcinoma with OGCs; whereas, in the other 3 cases, OGCs were not detected without the help of immunohistochemistry.

CONCLUSIONS: FNAC appeared to be a very efficient way to diagnose breast carcinoma with OGCs, because it detected forms with only a few OGCs that usually are not observed at histologic diagnosis. Consequently, the current results indicated that mammary carcinoma with OGCs may be more frequent than reported previously.}, } @article {pmid20942802, year = {2011}, author = {Boucher, D and Blais, V and Drag, M and Denault, JB}, title = {Molecular determinants involved in activation of caspase 7.}, journal = {Bioscience reports}, volume = {31}, number = {4}, pages = {283-294}, pmid = {20942802}, issn = {1573-4935}, support = {86563-1//Canadian Institutes of Health Research/Canada ; MOP-86563/CAPMC/CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Binding Sites ; Caspase 3/chemistry/genetics ; Caspase 7/*chemistry/genetics ; Caspase 8/chemistry/genetics ; Caspases/chemistry/genetics ; Caspases, Initiator/chemistry/genetics ; Cells, Cultured ; Dimerization ; Humans ; Kinetics ; Protein Structure, Tertiary ; }, abstract = {During apoptosis, initiator caspases (8, 9 and 10) activate downstream executioner caspases (3, 6 and 7) by cleaving the IDC (interdomain connector) at two sites. Here, we demonstrate that both activation sites, site 1 and site 2, of caspase 7 are suboptimal for activation by initiator caspases 8 and 9 in cellulo, and in vitro using recombinant proteins and activation kinetics. Indeed, when both sites are replaced with the preferred motifs recognized by either caspase 8 or 9, we found an up to 36-fold improvement in activation. Moreover, cleavage at site 1 is preferred to site 2 because of its location within the IDC, since swapping sites does not lead to a more efficient activation. We also demonstrate the important role of Ile195 of site 1 involved in maintaining a network of contacts that preserves the proper conformation of the active enzyme. Finally, we show that the length of the IDC plays a crucial role in maintaining the necessity of proteolysis for activation. In fact, although we were unable to generate a caspase 7 that does not require proteolysis for activity, shortening the IDC of the initiator caspase 8 by four residues was sufficient to confer a requirement for proteolysis, a key feature of executioner caspases. Altogether, the results demonstrate the critical role of the primary structure of caspase 7's IDC for its activation and proteolytic activity.}, } @article {pmid20934398, year = {2011}, author = {Visconti, G and Eltahir, Y and Van Ginkel, RJ and Bart, J and Werker, PM}, title = {Approach and management of primary ectopic breast carcinoma in the axilla: where are we? A comprehensive historical literature review.}, journal = {Journal of plastic, reconstructive & aesthetic surgery : JPRAS}, volume = {64}, number = {1}, pages = {e1-11}, doi = {10.1016/j.bjps.2010.08.015}, pmid = {20934398}, issn = {1878-0539}, mesh = {*Axilla ; Biopsy, Needle ; *Breast ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Chemotherapy, Adjuvant ; Choristoma/*diagnosis ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Italy ; Mastectomy, Segmental/methods ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rare Diseases ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {Primary ectopic breast carcinoma is a rare disease and, at present, no specific guidelines on its diagnosis and treatment are available. The purpose of this article is to review the world literature in English on primary ectopic breast carcinoma located in the armpit and to offer guidelines for diagnosis and treatment. Data for this review were identified by searches of MEDLINE, PubMed, The Cochrane Library, ACNP (Italian catalogue of journals) and references from relevant articles using relevant search terms and data published in the previous reviews. Primary ectopic breast carcinoma of the axilla mostly affects women of over 40 (range 28-90 yrs) years of age. The most frequent histological diagnosis is invasive ductal carcinoma not otherwise specified (NOS) (72%). Because of its rareness, in most cases, the diagnosis is delayed for on average 40.5 months. This disease is rare, but a high level of suspicion for carcinoma is mandatory when confronted with a tumour in this area. Once diagnosed, patients should undergo staging, and prognostic and adjuvant treatment procedures identical to orthotopic breast carcinoma guidelines. There are some limitations for the staging. Loco-regional treatment, on indication, combined with endocrine therapy and/or chemotherapy seems the treatment of choice.}, } @article {pmid20921957, year = {2011}, author = {Martens, FM and Heesakkers, JP and Rijkhoff, NJ}, title = {Minimal invasive electrode implantation for conditional stimulation of the dorsal genital nerve in neurogenic detrusor overactivity.}, journal = {Spinal cord}, volume = {49}, number = {4}, pages = {566-572}, doi = {10.1038/sc.2010.134}, pmid = {20921957}, issn = {1476-5624}, mesh = {Adult ; Electric Stimulation Therapy/*methods ; Electrodes, Implanted/standards ; Female ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods ; Muscle Contraction/physiology ; Spinal Cord Injuries/etiology/*physiopathology ; Urinary Bladder/innervation/physiopathology ; Urinary Bladder, Neurogenic/etiology/*physiopathology/*therapy ; Young Adult ; }, abstract = {STUDY DESIGN: Experimental.

OBJECTIVES: Electrical stimulation of the dorsal genital nerves (DGN) suppresses involuntary detrusor contractions (IDCs) in patients with neurogenic detrusor overactivity (DO). The feasibility of minimal invasive electrode implantation near the DGN and the effectiveness of conditional stimulation to suppress IDCs at different amplitudes in spinal cord injury (SCI) patients with DO were studied.

SETTING: Radboud University Nijmegen MC, The Netherlands.

METHODS: In eight healthy volunteers, a needle electrode was inserted from both a medial and lateral-to-midline site at the level of the pubic bone. Electrode insertion was guided by the genito-anal reflex (GAR) evoked by electrical stimulation and by sensation to this stimulation. In eight SCI patients with DO, the bladder was repeatedly filled and emptied partially in between. Conditional stimulation using a needle electrode was applied when an IDC was observed at urodynamics. Different amplitudes were used during each filling. Control cystometry was carried out before electrode insertion and after stimulation.

RESULTS: The lateral implant approach was preferred, as it was easier to manoeuvre the needle along the pubic bone and fixate the needle. In SCI patients, the electrode was positioned successfully, and IDCs were suppressed (range 1-6 IDC suppressions) with conditional stimulation at maximum tolerable amplitude, except for one patient. Stimulation was less effective at lower amplitudes. Stimulation lowered the intensity of bladder sensations concomitant with IDC.

CONCLUSION: The lateral-to-midline implant approach, in combination with GAR and sensation to stimulation, is feasible for electrode implantation near the DGN in SCI patients. Conditional stimulation effectively suppresses IDCs.}, } @article {pmid20920981, year = {2010}, author = {Xiang, G and Zhenkun, F and Shuang, C and Jie, Z and Hua, Z and Wei, J and Da, P and Dianjun, L}, title = {Association of DNMT1 gene polymorphisms in exons with sporadic infiltrating ductal breast carcinoma among Chinese Han women in the Heilongjiang Province.}, journal = {Clinical breast cancer}, volume = {10}, number = {5}, pages = {373-377}, doi = {10.3816/CBC.2010.n.049}, pmid = {20920981}, issn = {1938-0666}, mesh = {Adult ; Aged ; Alleles ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Chi-Square Distribution ; China ; Exons ; Female ; Haplotypes ; Humans ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Repressor Proteins/*genetics ; Tumor Suppressor Protein p53/metabolism ; Young Adult ; }, abstract = {BACKGROUND: Infiltrating ductal carcinoma (IDC) is the most common malignant breast cancer in women, and genetic factors appear to play a significant role in the susceptibility to IDC. Alteration of DNA methylation is an epigenetic change in human cancers, including breast cancer. DNA-methyltransferase 1 (DNMT1) is a major enzyme that determines genomic methylation patterns. In order to clarify the association of DNMT1 polymorphisms with IDC, a case-control study was conducted in women from the Heilongjiang Province, in the northeast of China.

PATIENTS AND METHODS: We scrutinized the 2 genetic polymorphisms in exons of DNMT1 that may influence the activity of DNMT1. Our research subjects consisted of 305 patients with IDC and 314 age-matched healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Data were analyzed using the χ2 test by SPSS, version 13.0, and Haploview, version 4.1. The association between DNMT1 polymorphisms and the clinical features of IDC was analyzed.

RESULTS: In rs16999593, the frequency of CT genotype and C allele were lower in patients than in controls (P = .028 and P = .017, respectively). Also, rs2228611 AG genotype was higher in patients than in controls (P = .015). The frequency of haplotype CA was lower in patients than in controls (P = .034). Significant association was shown between the 2 single nucleotide polymorphisms of the DNMT1 gene and progesterone receptor (PgR) and p53 status. No association was found between DNMT1 gene polymorphisms and tumor size or estrogen receptor status.

CONCLUSION: Our results was a previous study, which suggested that DNMT1 gene polymorphisms in exons may provide valuable information for predicting the sporadic IDC risk and may be associated with prognosis factors such as PgR and p53 status in Chinese Han women in the Heilongjiang Province.}, } @article {pmid20886042, year = {2010}, author = {Lo Presti, M and Ferro, A and Contino, F and Mazzarella, C and Sbacchi, S and Roz, E and Lupo, C and Perconti, G and Giallongo, A and Migliorini, P and Marrazzo, A and Feo, S}, title = {Myc promoter-binding protein-1 (MBP-1) is a novel potential prognostic marker in invasive ductal breast carcinoma.}, journal = {PloS one}, volume = {5}, number = {9}, pages = {e12961}, pmid = {20886042}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/*diagnosis/*genetics/metabolism/pathology ; Carcinoma, Ductal/*diagnosis/*genetics/metabolism/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/enzymology/genetics ; DNA-Binding Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Phosphopyruvate Hydratase/genetics/metabolism ; Prognosis ; Protein Transport ; }, abstract = {BACKGROUND: Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. α-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of α-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken.

METHODOLOGY AND FINDINGS: We analyzed α-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-α-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic α-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC.

CONCLUSIONS: MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer.}, } @article {pmid20853054, year = {2010}, author = {Bauman, L and Barth, RJ and Rosenkranz, KM}, title = {Breast conservation in women with multifocal-multicentric breast cancer: is it feasible?.}, journal = {Annals of surgical oncology}, volume = {17 Suppl 3}, number = {}, pages = {325-329}, doi = {10.1245/s10434-010-1247-1}, pmid = {20853054}, issn = {1534-4681}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Feasibility Studies ; Female ; Humans ; *Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: The incidence of preoperatively identified multifocal and multicentric breast cancer is rising with improved sensitivity of imaging modalities. Based on retrospective, historic data, breast conservation in women with multiple tumors has been discouraged because of high rates of local regional recurrence (LRR). These studies, however, do not extrapolate to contemporary practice as they do not incorporate the use of modern therapies and surgical techniques. This study is designed to evaluate the feasibility of breast conservation in women with multiple breast primaries.

MATERIALS AND METHODS: We retrospectively reviewed the charts of 22 women who underwent breast conservation surgery for 2 or more synchronous, ipsilateral cancers between 1998 and 2008. We extracted data including tumor size, nodal staging, receptor status, adjuvant therapies administered, and local-regional recurrence.

RESULTS: A total of 22 patients were identified. Average follow up is 3.5 years. One patient (4.5%) experienced an in-breast recurrence. Both initial tumors in this patient were invasive ductal carcinoma, ER/PR, negative and HER2 positive. Time to LRR was 2.5 years.

CONCLUSIONS: Our data are consistent with those of recent studies in which multifocal/multicentric local regional recurrence in multicentric/multifocal breast is equivalent to that seen in women with unifocal cancer. The single local recurrence in this study occurred in a premenopausal women with ER/PR- disease who were HER2+. Prior retrospective studies have identified ER/PR- and HER2 overexpression as independent risk factors for recurrence following breast conservation. Additional prospective trials are warranted to better assess the oncologic safety of breast conservation in this population.}, } @article {pmid20879052, year = {2010}, author = {Park, HS and Park, S and Kim, JH and Lee, JH and Choi, SY and Park, BW and Lee, KS}, title = {Clinicopathologic features and outcomes of metaplastic breast carcinoma: comparison with invasive ductal carcinoma of the breast.}, journal = {Yonsei medical journal}, volume = {51}, number = {6}, pages = {864-869}, pmid = {20879052}, issn = {1976-2437}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/*physiopathology ; Carcinoma/*diagnosis/*physiopathology ; Carcinoma, Ductal, Breast/*diagnosis/*physiopathology ; Female ; Humans ; Incidence ; Medical Oncology/methods ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other.

RESULTS: Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (> 2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups.

CONCLUSION: MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.}, } @article {pmid20878255, year = {2011}, author = {Sipola, P and Peuhkurinen, K and Vanninen, E}, title = {Comparison of gated single-photon emission computed tomography with magnetic resonance imaging for evaluation of left ventricular volumes and ejection fraction in patients with idiopathic dilated cardiomyopathy.}, journal = {The international journal of cardiovascular imaging}, volume = {27}, number = {4}, pages = {629-634}, pmid = {20878255}, issn = {1875-8312}, mesh = {Adolescent ; Adult ; Aged ; *Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography ; Cardiomyopathy, Dilated/*diagnosis/diagnostic imaging/pathology/physiopathology ; Female ; Finland ; Humans ; *Magnetic Resonance Imaging, Cine ; Male ; Middle Aged ; Organophosphorus Compounds ; Organotechnetium Compounds ; Predictive Value of Tests ; Prospective Studies ; Radiopharmaceuticals ; Reproducibility of Results ; *Stroke Volume ; *Ventricular Function, Left ; Young Adult ; }, abstract = {To prospectively compare the left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) obtained from gated perfusion single photon emission computed tomography (GSPECT) with those obtained from cardiac magnetic resonance imaging (MRI) in patients with idiopathic dilated cardiomyopathy (IDC). Twenty-one patients with IDC (6 females) with a median age of 45 years (range 17-65) were scheduled for (99m)Tc-tetrofosmin-GSPECT and MRI within a 3 h interval. In both methods LV volumes were analyzed with the Simpson method. Both GSPECT and MRI were successfully completed in 90% of patients. Close linear correlations were observed between the two methods in LVEDV (R = 0.918; P < 0.001) and LVESV (R = 0.946; P < 0.001), but correlations were significantly weaker in LVEF (R = 0.323; P = 0.082). LVEDV and LVESV were smaller in GSPECT than in MRI (161 ± 73 vs. 214 ± 87 ml, P < 0.001, and 116 ± 64 vs. 138 ± 72 ml, P < 0.001, respectively). In 4 patients (21%) the LVEDV index was considered normal by GSPECT and increased by MRI, if MRI-derived normal values were used. No difference was found between GSPECT and MRI when LVEF(MRI) was ≤ 40%, but GSPECT showed smaller LVEF when LVEF(MRI) was over 40% (33 ± 11 vs. 50 ± 5%; P < 0.05). The finding of increased LVEDV in GSPECT is reliable compared with MRI. However, LV volumes were underestimated by GSPECT and no direct comparisons can be made between methods in follow up studies. Abnormal results should be confirmed by another imaging modality, such as MRI, if these findings have therapeutic consequences.}, } @article {pmid20878073, year = {2010}, author = {Nie, F and Yu, XL and Wang, XG and Tang, YF and Wang, LL and Ma, L}, title = {Down-regulation of CacyBP is associated with poor prognosis and the effects on COX-2 expression in breast cancer.}, journal = {International journal of oncology}, volume = {37}, number = {5}, pages = {1261-1269}, doi = {10.3892/ijo_00000777}, pmid = {20878073}, issn = {1791-2423}, mesh = {Blotting, Western ; Breast Neoplasms/*genetics/metabolism/pathology ; Calcium-Binding Proteins/biosynthesis/*genetics ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cyclooxygenase 2/*genetics/metabolism ; Down-Regulation ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Calcyclin-binding protein (CacyBP) is a tumor suppressor in gastric and renal cell carcinoma, but an oncogene in pancreatic cancer. However, the function of CacyBP in breast cancer has not been well elucidated. In this study, we explored the clinical relevance of CacyBP and investigated the relationship between CacyBP and COX-2 in breast cancer. Immunohistochemical analysis in 172 cases of breast tissues showed that the positive rate of CacyBP protein expression in normal breast tissues (NBT) (89.3%) was higher than that in invasive ductal carcinoma (IDC) (56.1%) (P<0.05). RT-PCR and Western blot analysis showed that CacyBP mRNA and protein expression were significantly lower in tumor tissues as compared to those in the corresponding non-tumorous tissues (P<0.05). The expression trend of COX-2 was opposite with CacyBP in breast carcinogenesis. Moreover, the CacyBP expression was significantly negatively associated with the COX expression in the 132 breast cancer samples (correlation coefficient = 0.505, P<0.001). The clinicopathological data analysis in 132 breast cancer samples showed that CacyBP expression was positively correlated with well differentiated samples (P=0.021), low pathologic TNM stage (P=0.009), and no lymphatic metastasis (P=0.027) of patients with breast cancer. Furthermore, reduced CacyBP expression was associated with poor prognosis. Knockdown of CacyBP gene using siRNA enhanced the proliferation and invasion ability of breast cancer cells, which was dependent on COX-2 expression. In conclusion, CacyBP regulation of COX-2 expression may play an important role in human breast carcinogenesis. Restoration of CacyBP gene is a potential therapeutic target of breast cancer.}, } @article {pmid20878013, year = {2010}, author = {Martino, HF and Oliveira, PS and Souza, FC and Costa, PC and Assunção E Silva, E and Villela, R and Gaze, M and Weitzel, LH and Oliveira, A and Muccillo, FB and Arvelo, SN and Sá, R and Guimarães, TC and Tura, BR and Campos de Carvalho, AC}, title = {A safety and feasibility study of cell therapy in dilated cardiomyopathy.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {43}, number = {10}, pages = {989-995}, doi = {10.1590/s0100-879x2010007500093}, pmid = {20878013}, issn = {1414-431X}, mesh = {Adult ; Aged ; *Bone Marrow Transplantation ; Cardiomyopathy, Dilated/*surgery ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {The aim of this study was to determine if bone marrow mononuclear cell (BMMC) transplantation is safe for moderate to severe idiopathic dilated cardiomyopathy (IDC). Clinical trials have shown that this procedure is safe and effective for ischemic patients, but little information is available regarding non-ischemic patients. Twenty-four patients with IDC, optimized therapy, age 46 ± 11.6 years, 17 males, NYHA classes II-IV, and left ventricular ejection fraction <35% were enrolled in the study. Clinical evaluation at baseline and 6 months after stem cell therapy to assess heart function included echocardiogram, magnetic resonance imaging, cardiopulmonary test, Minnesota Quality of Life Questionnaire, and NYHA classification. After cell transplantation 1 patient showed a transient increase in enzyme levels and 2 patients presented arrhythmias that were reversed within 72 h. Four patients died during follow-up, between 6 and 12 weeks after therapy. Clinical evaluation showed improvement in most patients as reflected by statistically significant decreases in Minnesota Quality of Life Questionnaire (63 ± 17.9 baseline vs 28.8 ± 16.75 at 6 months) and in class III-IV NYHA patients (18/24 baseline vs 2/20 at 6 months). Cardiopulmonary exercise tests demonstrated increased peak oxygen consumption (12.2 ± 2.4 at baseline vs 15.8 ± 7.1 mL·kg[-1]·min[-1] at 6 months) and walked distance (377.2 ± 85.4 vs 444.1 ± 77.9 m at 6 months) in the 6-min walk test, which was not accompanied by increased left ventricular ejection fraction. Our findings indicate that BMMC therapy in IDC patients with severe ventricular dysfunction is feasible and that larger, randomized and placebo-controlled trials are warranted.}, } @article {pmid20869243, year = {2010}, author = {Li, JL and Wang, ZL and Su, L and Liu, XJ and Tang, J}, title = {Breast lesions with ultrasound imaging-histologic discordance at 16-gauge core needle biopsy: can re-biopsy with 10-gauge vacuum-assisted system get definitive diagnosis?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {6}, pages = {446-449}, doi = {10.1016/j.breast.2010.04.003}, pmid = {20869243}, issn = {1532-3080}, mesh = {Adult ; Aged ; Biopsy, Needle/instrumentation/*methods ; Breast/pathology ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia/pathology ; Middle Aged ; Predictive Value of Tests ; Ultrasonography ; }, abstract = {The aim of this study was to evaluate if re-biopsy with 10-gauge vacuum-assisted biopsy (VAB) could get definitive diagnosis for breast lesions with ultrasound (US) imaging-histologic discordance at 16-gauge core needle biopsy (CNB). From January 2007 to June 2008, a consecutive biopsy was performed on 1069 lesions with US-guided 16-gauge CNB. A total of 28 lesions were considered to be US imaging-histologic discordant and all of them underwent subsequent 10-gauge VAB. All malignant lesions located at VAB were treated with subsequent surgery and all benign lesions at VAB were followed up for at least 1 year. Six of the 28 lesions (21.4%) had pathologic upgrade after VAB. In them, one case upgraded from adenosis to ductal carcinoma in situ (DCIS); one case upgraded from adenosis to infiltrating ductal carcinoma (IDC); one case upgraded from atypical ductal hyperplasia to IDC; two cases upgraded from intraductal papilloma to DCIS; and one case upgraded from sclerosing adenosis to invasive lobular carcinoma (ILC). The subsequent surgery further demonstrated the diagnosis of VAB for all the lesions with histologic upgrade. Re-biopsy could improve diagnostic accuracy in patients with breast lesions showing imaging-histologic discordance during CNB, and 10-gauge VAB was a valuable method to deal with re-biopsy.}, } @article {pmid20864896, year = {2010}, author = {Hershberger, RE and Morales, A and Siegfried, JD}, title = {Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals.}, journal = {Genetics in medicine : official journal of the American College of Medical Genetics}, volume = {12}, number = {11}, pages = {655-667}, pmid = {20864896}, issn = {1530-0366}, support = {R01 HL058626/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Age of Onset ; Cardiomyopathy, Dilated/classification/*diagnosis/epidemiology/*genetics ; Genes ; *Genetic Counseling ; Genetic Testing ; Humans ; Pedigree ; }, abstract = {Dilated cardiomyopathy (DCM), usually diagnosed as idiopathic dilated cardiomyopathy (IDC), has been shown to have a familial basis in 20-35% of cases. Genetic studies in familial dilated cardiomyopathy (FDC) have shown dramatic locus heterogeneity with mutations identified in >30 mostly autosomal genes showing primarily dominant transmission. Most mutations are private missense, nonsense or short insertion/deletions. Marked allelic heterogeneity is the rule. Although to date most DCM genetics fits into a Mendelian rare variant disease paradigm, this paradigm may be incomplete with only 30-35% of FDC genetic cause identified. Despite this incomplete knowledge, we predict that DCM genetics will become increasingly relevant for genetics and cardiovascular professionals. This is because DCM causes heart failure, a national epidemic, with considerable morbidity and mortality. The fact that early, even pre-symptomatic intervention can prevent or ameliorate DCM, coupled with more cost-effective genetic testing, will drive further progress in the field. Ongoing questions include: whether sporadic (IDC) disease has a genetic basis, and if so, how it differs from familial disease; which gene-specific or genetic pathways are most relevant; and whether other genetic mechanisms (e.g., DNA structural variants, epigenetics, mitochondrial mutations and others) are operative in DCM. We suggest that such new knowledge will lead to novel approaches to the prevention and treatment of DCM.}, } @article {pmid20860963, year = {2010}, author = {Szabó, J and Falkus, B and Simon, E and Brünner, S and Baranyay, F}, title = {[Late gastrointestinal metastases of invasive lobular breast carcinoma mimicking Crohn's disease].}, journal = {Orvosi hetilap}, volume = {151}, number = {40}, pages = {1666-1671}, doi = {10.1556/OH.2010.28927}, pmid = {20860963}, issn = {0030-6002}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/chemistry/*secondary ; Carcinoma, Lobular/chemistry/*secondary ; Crohn Disease/*diagnosis ; Diagnosis, Differential ; Female ; Gastrointestinal Neoplasms/chemistry/*diagnosis/*secondary ; Humans ; Middle Aged ; }, abstract = {Invasive lobular carcinoma--comprising approximately 10 percent of breast cancers--is considered to be a histologically, molecular genetically, clinically distinct entity metastasizing mainly the gastrointestinal tract. Gastrointestinal system is much more likely involved in advanced invasive lobular carcinoma, than it is in invasive ductal carcinoma. They manifest after 3-20 years from the recognition of the primary tumor and they appear to be inflammatory disease or a secondary tumor. Here we show the case of a female patient with breast cancer, who died at the age of 53 years. 8 years after tumor-free state upper abdominal spastic pain emerged irradiating into the back with belt-like pattern. Radiologically, Crohn's disease was diagnosed. Ileum biopsy was negative. Patient was treated ex juvantibus with methylprednisolon. In the background of mechanic ileus the resection of the terminal ileum and partly the ascended colon was surgically removed. The patient died in 3 weeks after the operation. Microscopically the thickened wall of the terminal ileum showed diffuse small cell carcinomatous infiltration. Immuno-histochemically the metastatic carcinoma cells were reacting with Breast Carcinoma Antigen (BRCA 1) and CA 15-3. The patient had AB blood group according to her red blood cell phenotype. Lectins and monoclonal antibodies with ABH blood group specificity reacted strongly with the metastatic carcinoma cells.}, } @article {pmid20854466, year = {2010}, author = {Pal, R and Marwaha, S and Pepponi, I and Mann, JF and Paul, MJ and Reljic, R}, title = {Generation of self-renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cells.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {118}, number = {10}, pages = {729-738}, doi = {10.1111/j.1600-0463.2010.02650.x}, pmid = {20854466}, issn = {1600-0463}, mesh = {Animals ; Antigen Presentation ; Antigens, Bacterial/immunology ; Cell Culture Techniques ; Dendritic Cells/cytology/*immunology ; Female ; Flow Cytometry ; Lymphocyte Activation ; Lymphoid Progenitor Cells/cytology/*immunology ; Mice ; Mice, Inbred BALB C ; Mycobacterium/*immunology ; Spleen/cytology/*immunology ; T-Lymphocytes/cytology/immunology ; Tuberculosis/*immunology ; }, abstract = {Dendritic cells (DC) play a key role in driving the adaptive immune response to Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB). However, studying these important yet very sparse immune cells in the context of MTB pathogenesis is severely restricted by the lack of suitable cell lines and the complexity of culturing of DC progenitors, usually obtained from the bone marrow. However, significant advances have been made towards generating long-term DC cultures from various lymphoid tissues. Here, we report the evidence for generating a long-term, self-renewing DC culture from the Balb/c mouse spleen. We demonstrate that these cells, termed IDC-3, have a myeloid DC origin, i.e. they are CD11c(+) CD11b(++) CD8-α(-) F4/80(+/-) and that they also display a phenotype MHC-II(+) CD16/32(++) CD80(+/-) CD86(+) , indicating that they are immature DC. Following incubation with Mycobacterium bovis BCG (Bacillus Calmette Guerin), the IDC-3 efficiently took up bacteria and acquired the morphology of mature DC. Importantly though, when IDC-3 were pre-stimulated with a mycobacterial antigen in vitro, they were able to induce proliferation of T lymphocytes from mice immunized with the same antigen. The T-cell stimulatory potential of IDC-3 was further enhanced when the cells were co-stimulated with an anti-CD40 mAb. We therefore suggest that the IDC-3 culture system could be a useful tool for studying the interaction of DC with mycobacteria.}, } @article {pmid20846267, year = {2010}, author = {Lee, YH and Dai, YC and Lin, IL and Tu, CW}, title = {Young-aged woman with invasive ductal carcinoma arising in atypical microglandular adenosis: a case report.}, journal = {Pathology international}, volume = {60}, number = {10}, pages = {685-689}, doi = {10.1111/j.1440-1827.2010.02577.x}, pmid = {20846267}, issn = {1440-1827}, mesh = {Adult ; Breast Neoplasms/complications/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/complications/metabolism/*pathology/therapy ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/complications/metabolism/*pathology/therapy ; Humans ; Immunohistochemistry ; Mastectomy, Segmental ; }, abstract = {Microglandular adenosis (MGA) and atypical microglandular adenosis (AMGA) are extremely rare and unique forms of adenosis of the breast. Both forms of adenosis are strongly associated with carcinoma arising in microglandular adenosis (MGACA) and are recognised as precursor lesions of invasive breast carcinoma. Here we provide a clinical report of a young Taiwanese woman who was diagnosed with MGACA and AMGA by means of echo-guided core biopsy. The subsequent lumpectomy revealed a spectrum of lesions ranging from MGA and AMGA to ductal carcinoma in situ (DCIS) and invasive carcinoma. All of the above lesions have similar immunohistochemical results (expression of S-100 protein, the absence of oestrogen receptors, progesterone receptors and Her2/neu, and the lack of p63 and the smooth muscle myosin-heavy chain) with a rather different Ki-67 labelling proliferation index. This report is of practical interest because the diagnosis of AMGA and MGACA had already been made via needle biopsy.}, } @article {pmid20843442, year = {2010}, author = {Sanguinetti, A and Ragusa, M and Calzolari, F and D'Ajello, F and Fioriti, L and Papini, D and Sidoni, A and Roila, F and Avenia, N}, title = {Invasive ductal carcinoma arising in ectopic breast tissue of the axilla. Case report and review of the literature.}, journal = {Il Giornale di chirurgia}, volume = {31}, number = {8-9}, pages = {383-386}, pmid = {20843442}, issn = {0391-9005}, mesh = {*Axilla ; *Breast ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Chemotherapy, Adjuvant ; Choristoma/*diagnosis/surgery ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/therapy ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence. Most reported cases have involved ductal carcinoma, but other types, such as medullary, papillary, and lobular carcinomas, have been described. For pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue can be difficult, especially in the axilla, where carcinoma of adnexal origin must be excluded. We describe a 51-year-old woman who developed invasive secretory ductal carcinoma in ectopic left axillary breast tissue and micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma arose in a left axillary mass that had been present for several years, from which she had secreted fluid during prior menstrual periods.}, } @article {pmid20836339, year = {2010}, author = {Schneider, C and Trocha, S and McKinley, B and Shaw, J and Bielby, S and Blackhurst, D and Jones, Y and Cornett, W}, title = {The use of sentinel lymph node biopsy in ductal carcinoma in situ.}, journal = {The American surgeon}, volume = {76}, number = {9}, pages = {943-946}, pmid = {20836339}, issn = {0003-1348}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Middle Aged ; Patient Selection ; Reoperation ; *Sentinel Lymph Node Biopsy ; }, abstract = {Although ductal carcinoma in situ (DCIS) does not require axillary evaluation, controversy exists regarding the use of sentinel lymph node biopsy (SLNB) in patients with DCIS diagnosed by core needle biopsy (CNB). Advocates of concomitant SLNB and lumpectomy cite the low morbidity of SLNB, the high rate of invasive ductal carcinoma in resected specimens, and the positive nodes found in 1 to 2 per cent of patients with resected DCIS despite finding no invasive component. Opponents of this practice cite the complication risk and the improbability of clinically significant axillary recurrence. We therefore proposed to determine our rate of invasive cancer in DCIS diagnosed by CNB and to determine whether SLNB at first operation would decrease return to the operating room. We retrospectively reviewed patients diagnosed with DCIS by CNB from 2003 to 2008. Standard clinicopathological data were collected and analyzed. In 110 patients, the prevalence of invasive cancer on final resection pathology was 13.6 per cent (15 of 110). Of those patients with invasive cancer, 93 per cent (14 of 15) had high-grade DCIS (P = 0.077) by CNB. Seventeen per cent (14 of 82) of patients with high-grade DCIS had invasive cancer. Of 34 patients with SLNB, three (9%) had positive nodes. Fifteen patients required re-excision to obtain negative margins, including 13 patients with invasive cancer. Five patients (4.5%) were spared additional operative intervention by initially performing SLNB. We suggest using concomitant SLNB when a high clinical suspicion of invasive cancer exists, in the presence of a palpable mass, or when mastectomy precludes future SLNB. Intraoperative margin assessment is needed to avoid return to the operating room.}, } @article {pmid20835647, year = {2010}, author = {Bagnoli, F and Oliveira, VM and Silva, MA and Taromaru, GC and Rinaldi, JF and Aoki, T}, title = {The interaction between aromatase, metalloproteinase 2,9 and CD44 in breast cancer.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {56}, number = {4}, pages = {472-477}, doi = {10.1590/s0104-42302010000400023}, pmid = {20835647}, issn = {1806-9282}, mesh = {Aromatase/analysis/metabolism ; Breast Neoplasms/*metabolism ; Carcinoma in Situ/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Humans ; Hyaluronan Receptors/analysis/metabolism ; Immunohistochemistry ; Matrix Metalloproteinase 2/analysis/metabolism ; Matrix Metalloproteinase 9/analysis/metabolism ; Neoplasm Proteins/*metabolism ; }, abstract = {OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and CD44 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) when both are found in the same breast.

METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA) and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 polyclonal antibodies and anti-CD44 monoclonal antibodies.

RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3%) and 60 (67%) of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60%) cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50%) and 82 (74.50%) cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50%) and 48 (42.60%) of the cases, respectively; all of them were highly correlated (p<0,001). The correlation analysis found positive, statistically significant correlation, in IDC between aromatase and MMP-2 (p<0.001) and between aromatase and MMP-9 (p=0.034). Positive correlation between aromatase and MMP-2 (p<0.001) and between MMP-9 and CD44 (p=0.030) were found in DCIS.

CONCLUSION: These results allow us to conclude that aromatase through local estrogen synthesis in breast tissue plays an important role in breast carcinogenesis, mainly influencing MMP-2 and MMP-9 which are important participants in tumor cell invasion and dependence of their connection to CD44 for action.}, } @article {pmid20834237, year = {2010}, author = {Lwin, ZM and Guo, C and Salim, A and Yip, GW and Chew, FT and Nan, J and Thike, AA and Tan, PH and Bay, BH}, title = {Clinicopathological significance of calreticulin in breast invasive ductal carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {12}, pages = {1559-1566}, doi = {10.1038/modpathol.2010.173}, pmid = {20834237}, issn = {1530-0285}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis/metabolism ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology ; Calreticulin/analysis/*biosynthesis ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Young Adult ; }, abstract = {Calreticulin is a chaperone protein located in the lumen of the endoplasmic reticulum. The association of calreticulin with pathological conditions such as autoimmune disorders and certain types of cancer have been reported. However, little is known about its role in the pathogenesis of breast cancer. The aim of this study was to determine the expression of calreticulin in vitro and correlate its expression levels in breast cancer tissue samples with clinicopathological parameters. Calreticulin expression was evaluated in MCF-7 and MDA-MB-231 breast cancer cells by real-time RT-PCR, Western blot, immunohistochemistry, and immunofluorescence staining. Patient tissue microarrays were constructed from 228 breast cancer specimens for immunohistochemical analysis. The in vitro study showed a higher calreticulin expression in more aggressive MDA-MB-231 cells as compared with MCF-7 cells at both mRNA and protein levels. In all, 227 out of 228 breast cancer samples exhibited calreticulin staining in at least 5% of the cancer cells. Calreticulin immunostaining was observed to be localized to the cytoplasm of the cancer cells. Regression analysis of calreticulin immunostaining in the tissue microarrays revealed that its expression was positively correlated to logarithm of (log) tumor size (P=0.046) and development of distant metastasis (P=0.017). Multivariate analysis confirmed calreticulin expression as an independent predictor of log tumor size and occurrence of distant metastasis. The data suggest that calreticulin expression is associated with more advanced tumors and is a potential prognostic biomarker.}, } @article {pmid20834076, year = {2010}, author = {Burkadze, G and Khardzeishvili, O and Gudadze, M and Tsikhiseli, G and Turashvili, G}, title = {Immunohistochemical expression of BRCA1 protein in invasive ductal carcinoma of the breast.}, journal = {Georgian medical news}, volume = {}, number = {184-185}, pages = {51-60}, pmid = {20834076}, issn = {1512-0112}, mesh = {Adult ; Aged ; BRCA1 Protein/*biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Young Adult ; }, abstract = {Immunohistochemically detected BRCA1 positivity has been reported to indicate the presence of full-length functional protein, while immunohistochemical negativity may be a result of sporadic BRCA1 mutation. We set out to study the immunohistochemical expression of BRCA1 protein in breast cancer and assess associations with lymph node status, histologic grade and expression of other biomarkers. We examined 100 patients aged from 21 to 71 years diagnosed with invasive ductal carcinoma. Immunohistochemistry was performed using anti-BRCA1, ER, PR, HER2/neu, and Ki-67 (MIB-1) antibodies. Cytoplasmic or nuclear-cytoplasmic BRCA1 expression was identified in a total of 64 breast cancer patients. None of the breast cancer tissue samples showed solely nuclear BRCA1 immunoreactivity. BRCA1 expression was associated with higher histologic grade, and majority of BRCA1-positive patients were below 50 years of age. Most BRCA1-negative patients had intermediate grade tumors. BRCA1 expression was positively associated with ER and PR positivity, and negatively associated with HER2/neu overexpression. Although immunohistochemistry can be an inexpensive and valuable preliminary method for detecting the BRCA1 status, BRCA1 protein localization is a complex issue. Well designed studies are needed to further investigate the performance of various anti-BRCA1 antibodies in formalin- fixed paraffin-embedded tissue samples, assess their association with BRCA1 gene mutations and determine clinical usefulness of BRCA1 immunohistochemistry.}, } @article {pmid20830525, year = {2010}, author = {Lage, S and Bueno, M and Andrade, F and Prieto, JA and Delgado, C and Legarda, M and Sanjurjo, P and Aldámiz-Echevarría, LJ}, title = {Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density.}, journal = {Journal of inherited metabolic disease}, volume = {33 Suppl 3}, number = {}, pages = {S363-71}, doi = {10.1007/s10545-010-9189-0}, pmid = {20830525}, issn = {1573-2665}, mesh = {Absorptiometry, Photon ; Adolescent ; Adult ; Biomarkers/blood ; *Bone Density ; Bone Diseases, Metabolic/blood/diagnosis/*etiology/physiopathology ; Calcium/blood ; Case-Control Studies ; Child ; Cross-Sectional Studies ; Diet, Protein-Restricted/*adverse effects ; Docosahexaenoic Acids/blood ; Eicosapentaenoic Acid/blood ; Fatty Acids/*blood ; Female ; Femur Neck/diagnostic imaging/*physiopathology ; Humans ; Lumbar Vertebrae/diagnostic imaging/*physiopathology ; Male ; Nutritional Status ; Osteoporosis/blood/diagnosis/*etiology/physiopathology ; Phenylalanine/blood ; Phenylketonurias/blood/diagnosis/*diet therapy/physiopathology ; Risk Factors ; Vitamin D/analogs & derivatives/blood ; Young Adult ; }, abstract = {BACKGROUND: Patients with phenylketonuria (PKU) undergo a restrictive vegan-like diet, with almost total absence of n-3 fatty acids, which have been proposed as potential contributors to bone formation in the healthy population. The PKU diet might lead these patients to bone mass loss and, consequently, to the development of osteopenia/osteoporosis. Therefore, we proposed to analyze their plasma fatty acid profile status and its relationship with bone health.

METHODS: We recruited 47 PKU patients for this cross-sectional study and divided the cohort into three age groups (6-10 years, 11-18 years, 19-42 years). We measured their plasma fatty acid profile and bone mineral density (BMD) (both at the femoral neck and the lumbar spine). Seventy-seven healthy controls also participated as reference values of plasma fatty acids.

RESULTS: Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and total n-3 fatty acids were significantly diminished in PKU patients compared with healthy controls. DHA, EPA, and total n-3 fatty acids were also positively associated with bone mineral density (r = 0.83, p = 0.010; r = 0.57, p = 0.006; r = 0.73, p = 0.040, respectively). There was no association between phenylalanine (Phe), Index of Dietary Control (IDC), calcium, 25-hydroxivitamin D concentrations, daily calcium intake, and BMD.

CONCLUSION: Our results suggest a possible influence of essential fatty acids over BMD in PKU patients. The lack of essential n-3 fatty acids intake in the PKU diet might affect bone mineralization. Further clinical trials are needed to confirm the effect of the n-3 essential fatty acids on bone accrual in a cohort of PKU patients.}, } @article {pmid20828490, year = {2010}, author = {Bin, WS and Richardson, S and Yeow, PH}, title = {An ergonomics study of a semiconductors factory in an IDC for improvement in occupational health and safety.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {16}, number = {3}, pages = {345-356}, doi = {10.1080/10803548.2010.11076849}, pmid = {20828490}, issn = {1080-3548}, mesh = {Accidents, Occupational/*prevention & control ; *Ergonomics ; Health Promotion/*methods ; Humans ; Industry ; Malaysia ; Noise, Occupational/prevention & control ; Occupational Diseases/*prevention & control ; *Occupational Health ; *Semiconductors ; Vision, Ocular ; }, abstract = {The study aimed to conduct an ergonomic intervention on a conventional line (CL) in a semiconductor factory in Malaysia, an industrially developing country (IDC), to improve workers' occupational health and safety (OHS). Low-cost and simple (LCS) ergonomics methods were used (suitable for IDCs), e.g., subjective assessment, direct observation, use of archival data and assessment of noise. It was found that workers were facing noise irritation, neck and back pains and headache in the various processes in the CL. LCS ergonomic interventions to rectify the problems included installing noise insulating covers, providing earplugs, installing elevated platforms, slanting visual display terminals and installing extra exhaust fans. The interventions cost less than 3 000 USD but they significantly improved workers' OHS, which directly correlated with an improvement in working conditions and job satisfaction. The findings are useful in solving OHS problems in electronics industries in IDCs as they share similar manufacturing processes, problems and limitations.}, } @article {pmid20825713, year = {2010}, author = {Qian, ZP and Li, N and Zhu, MQ and Zheng, JM and Zhang, YJ and Li, Q and Chen, MQ and Wang, JF and Shi, GF}, title = {[Expression of nuclear factor-κB and its regulated cytokines in dendritic cells in patients with chronic severe hepatitis B and its clinical significance].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {18}, number = {8}, pages = {590-594}, doi = {10.3760/cma.j.issn.1007-3418.2010.08.010}, pmid = {20825713}, issn = {1007-3418}, mesh = {Adult ; Case-Control Studies ; Cytokines/*metabolism ; Dendritic Cells/*metabolism ; Female ; Hepatitis B, Chronic/blood/*metabolism ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; NF-kappa B/*metabolism ; }, abstract = {OBJECTIVE: To investigate the correlation of nuclear factor-κB (NF-κB) level and its regulated cytokines in monocyte-derived dendritic cells (MoDC) with illness severity and prognosis in patients with chronic severe hepatitis B (CSHB).

METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll density gradient separation from 37 patients with CSHB, 20 chronically HBV-infected patients, and 20 normal controls. Monocytes were acquired using immunomagnetic anti-CD14-beads. Next, monocytes were induced into immature DC (iDC) in vitro. On day six, polyI:C was added to induce DC maturation. Then mature DCs (mDCs) were collected at 48 h after polyI:C treatment to test the expression of NF-κB p50 by real time PCR. The supernatants were also collected respectively. The expression of TNFα and IL-6 in the supernatants were measured by ELISA.

RESULTS: The expression of NF-κB p50 in mDCs of patients with CSHB was the highest in three groups (F=19.01, P<0.01). The secretion of TNFα and IL-6 in mDCs from group CSHB was extremely high when compared with the other two groups, the secretions of TNFα in groups CSHB, CHB and NC were(15317.69+/-4124.90) pg/ml, (9670.29+/-3654.68) pg/ml and (6547.43+/-1027.20) pg/ml (F=45.77, P<0.01) respectively, and the productions of IL-6 in groups CSHB, CHB and NC were (1423.78+/-375.14) pg/ml, (862.68+/-93.68) pg/ml and (567.26+/-167.04) pg/ml (F = 67.60, P is less than 0.01), respectively. NF-κB p50 showed significant correlations with TNFα(r=0.52, P<0.01) and IL-6 (r=0.65, P<0.01) in mDCs. Furthermore, the secretions of TNFα and IL-6 in mDCs from group CSHB were negatively associated with PTA (r=-0.41, P=0.01; r=-0.40, P=0.01), but not with ALT, TBil and virus loads (r=-0.03, P=0.85, r=0.01, P=0.93, r=0.01, P=0.95; r=-0.09, P=0.58, r=0.16, P=0.34, r=0.09, P=0.59). No significant difference found in the expression of TNFα and IL-6 between the survival subgroup and the death subgroup in group CSHB (t=0.42, P=0.67; t=0.76, P=0.45).

CONCLUSIONS: The expression levels of NF-κB and its regulated cytokines in monocyte-derived DCs in patients with chronic severe hepatitis B were up-regulated and perhaps associated positively with the illness severity.}, } @article {pmid20816984, year = {2010}, author = {Luncsford, PJ and Chang, DY and Shi, G and Bernstein, J and Madabushi, A and Patterson, DN and Lu, AL and Toth, EA}, title = {A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions.}, journal = {Journal of molecular biology}, volume = {403}, number = {3}, pages = {351-370}, pmid = {20816984}, issn = {1089-8638}, support = {R56 CA078391/CA/NCI NIH HHS/United States ; R01 GM035132/GM/NIGMS NIH HHS/United States ; CA78391/CA/NCI NIH HHS/United States ; GM35132/GM/NIGMS NIH HHS/United States ; R01 CA078391/CA/NCI NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/genetics/*metabolism ; DNA/genetics/metabolism ; DNA Damage ; DNA Glycosylases/*chemistry/genetics/*metabolism ; DNA Repair ; Exonucleases/genetics/*metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Mutation/genetics ; Protein Binding ; Schizosaccharomyces/genetics/growth & development/metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; }, abstract = {The DNA glycosylase MutY homologue (MYH or MUTYH) removes adenines misincorporated opposite 8-oxoguanine as part of the base excision repair pathway. Importantly, defects in human MYH (hMYH) activity cause the inherited colorectal cancer syndrome MYH-associated polyposis. A key feature of MYH activity is its coordination with cell cycle checkpoint via interaction with the Rad9-Rad1-Hus1 (9-1-1) complex. The 9-1-1 complex facilitates cell cycle checkpoint activity and coordinates this activity with ongoing DNA repair. The interdomain connector (IDC, residues 295-350) between the catalytic domain and the 8-oxoguanine recognition domain of hMYH is a critical element that maintains interactions with the 9-1-1 complex. We report the first crystal structure of a eukaryotic MutY protein, a fragment of hMYH (residues 65-350) that consists of the catalytic domain and the IDC. Our structure reveals that the IDC adopts a stabilized conformation projecting away from the catalytic domain to form a docking scaffold for 9-1-1. We further examined the role of the IDC using Schizosaccharomyces pombe MYH as model system. In vitro studies of S. pombe MYH identified residues I261 and E262 of the IDC (equivalent to V315 and E316 of the hMYH IDC) as critical for maintaining the MYH/9-1-1 interaction. We determined that the eukaryotic IDC is also required for DNA damage selection and robust enzymatic activity. Our studies also provide the first evidence that disruption of the MYH/9-1-1 interaction diminishes the repair of oxidative DNA damage in vivo. Thus, preserving the MYH/9-1-1 interaction contributes significantly to minimizing the mutagenic potential of oxidative DNA damage.}, } @article {pmid20815046, year = {2010}, author = {Lacroix-Triki, M and Suarez, PH and MacKay, A and Lambros, MB and Natrajan, R and Savage, K and Geyer, FC and Weigelt, B and Ashworth, A and Reis-Filho, JS}, title = {Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.}, journal = {The Journal of pathology}, volume = {222}, number = {3}, pages = {282-298}, doi = {10.1002/path.2763}, pmid = {20815046}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adenocarcinoma, Mucinous/*genetics/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Chromosome Aberrations ; Cluster Analysis ; Comparative Genomic Hybridization/methods ; Female ; Gene Amplification ; Gene Expression Profiling/methods ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Oncogenes ; }, abstract = {Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the molecular level to pure mucinous cancers, suggesting that mixed mucinous carcinomas may be best classified as variants of mucinous cancers rather than of IDC-NSTs.}, } @article {pmid20809021, year = {2010}, author = {Pleşan, DM and Georgescu, CV and Pătrană, N and Pleşan, C and Stoica, D}, title = {Immunohistochemical study of p53 and Ki67 in a group of patients with mammary carcinoma.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {51}, number = {3}, pages = {459-465}, pmid = {20809021}, issn = {2066-8279}, mesh = {Aged ; Breast Neoplasms/*metabolism/*pathology ; Cytoplasm/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Middle Aged ; Phenotype ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The study was done over a period of 10 years, 1996-2005 and it included 562 mammary cancer patients. Of the 562 cases, 100 cases of invasive mammary carcinoma included in this study were investigated from an immunohistochemical point of view. The p53 overexpression was more frequently seen in patients under 50 (23 cases, that is 54.76%), compared to those over 50 years old (19 cases, that is 45.24%). The positive p53 tumors were more often over 2 cm big. The invasive ductal carcinomas were p53-positive in 40 cases (44.44%) of all invasive ductal carcinoma cases, and the invasive lobular carcinomas were only positive in two cases (20%) of all mammary invasive lobular carcinoma cases. Most cases that had the overexpression of the p53-protein (30 cases that is 71.43%) had a high histological degree (G3), and only 12 cases (28.57%) had a low histological degree (G1 and G2). The overexpression of the p53-protein was present in all cases that had a heterogeneous phenotype (with one of the hormonal receptors being negative), in over half of the cases that had both hormonal receptors negative (59.37% of ER-/PR- phenotype cases) and in only 21.05% of cases that had ER+/PR+ phenotype. The association of the p53 overexpression (p53 over 10%), with the HER2 (2+ or 3+ score) overexpression was seen in seven patients of the 100 invasive mammary carcinoma cases included in this study. Consequently, 16.66% of p53 positive cases had associated positivity for HER2. Most cases that were p53 positive had an increased proliferation activity, as determined with Ki67. The Ki67 immunostaining analysis has made it clear that this marker has positivity presence in all cases. The vast majority of cases had a nuclear marking to Ki67, but two cases (2% of cases) had a cytoplasmatic / membrane staining.}, } @article {pmid20808831, year = {2010}, author = {Chen, J and Gomes, AR and Monteiro, LJ and Wong, SY and Wu, LH and Ng, TT and Karadedou, CT and Millour, J and Ip, YC and Cheung, YN and Sunters, A and Chan, KY and Lam, EW and Khoo, US}, title = {Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer.}, journal = {PloS one}, volume = {5}, number = {8}, pages = {e12293}, pmid = {20808831}, issn = {1932-6203}, support = {12011/CRUK_/Cancer Research UK/United Kingdom ; 2007NOVPHD16/BCN_/Breast Cancer Now/United Kingdom ; C37/A5606/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Active Transport, Cell Nucleus/drug effects ; Breast Neoplasms/*diagnosis/genetics/*metabolism/pathology ; Carcinoma, Ductal/diagnosis/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/drug effects/*metabolism ; Cell Proliferation/drug effects ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Phosphorylation/drug effects ; Prognosis ; Proto-Oncogene Proteins c-akt/*metabolism ; Survival Analysis ; Tamoxifen/pharmacology ; }, abstract = {BACKGROUND: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis.

Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway.

CONCLUSIONS/SIGNIFICANCE: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models.}, } @article {pmid20799942, year = {2010}, author = {Hawthorn, L and Luce, J and Stein, L and Rothschild, J}, title = {Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {460}, pmid = {20799942}, issn = {1471-2407}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; *Chromosome Aberrations ; Comparative Genomic Hybridization ; DNA, Neoplasm ; Female ; *Gene Dosage ; *Gene Expression Profiling ; Humans ; *Loss of Heterozygosity ; Lymphatic Metastasis ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'.

METHODS: We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs). Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH) analysis to identify genes showing altered expression in LOH regions.

RESULTS: Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples.

CONCLUSION: We have demonstrated the utility of the application of integrated analysis using high resolution CGH and whole genome transcript analysis for detecting driver genes in IDC. The high resolution platform allowed a refined demarcation of CNAs and gene expression profiling provided a mechanism to detect genes directly impacted by the CNA. This is the first report of LOH integrated with gene expression in IDC using a high resolution platform.}, } @article {pmid20799018, year = {2010}, author = {Tozaki, M and Yamashiro, N and Sakamoto, M and Sakamoto, N and Mizuuchi, N and Fukuma, E}, title = {Magnetic resonance-guided vacuum-assisted breast biopsy: results in 100 Japanese women.}, journal = {Japanese journal of radiology}, volume = {28}, number = {7}, pages = {527-533}, pmid = {20799018}, issn = {1867-108X}, mesh = {Adult ; Aged ; Biopsy/*methods ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Interpretation, Computer-Assisted ; Japan ; *Magnetic Resonance Angiography ; Middle Aged ; Retrospective Studies ; Vacuum ; }, abstract = {PURPOSE: The aim of this study was to clarify the frequency of malignancy and the histopathological characteristics of the lesions in patients undergoing magnetic resonance imaging (MRI)-guided vacuum-assisted biopsy (VAB).

MATERIALS AND METHODS: A retrospective review of 100 consecutive patients with 102 lesions who had undergone MRI-guided VAB was performed. The biopsies were performed on a 1.5-T MR scanner using a commercially available biopsy system. None of the lesions seen with MRI could be detected by mammography or second-look ultrasonography.

RESULTS: The average lesion sizes of the focus, mass, and nonmass lesions before the biopsy were 4.5, 8.2, and 21 mm, respectively. Twelve patients (12%) had lesions located in the deep portion of the breast, close to the pectoral muscle. The biopsy was successfully performed without important side effects in all patients. Histopathological findings were invasive ductal carcinoma in 6 (6%), in situ carcinoma in 28 (27%), and high-risk and benign in 68 (67%). Two high-risk lesions were upgraded to ductal carcinoma in situ (DCIS), and three DCIS lesions were upgraded to invasive ductal carcinoma at surgical excision.

CONCLUSION: The high rate of DCIS might be a unique feature among Japanese women. However, MRI-guided VAB is necessary for MRI-only visible suspicious lesions in Japan.}, } @article {pmid20795760, year = {2011}, author = {Whiteside, TL and Griffin, DL and Stanson, J and Gooding, W and McKenna, D and Sumstad, D and Kadidlo, D and Gee, A and Durett, A and Lindblad, R and Wood, D and Styers, D}, title = {Shipping of therapeutic somatic cell products.}, journal = {Cytotherapy}, volume = {13}, number = {2}, pages = {201-213}, pmid = {20795760}, issn = {1477-2566}, support = {N01HB37166/HL/NHLBI NIH HHS/United States ; N01HB37164/HL/NHLBI NIH HHS/United States ; N01-HB-37165/HB/NHLBI NIH HHS/United States ; N01HB37165/HL/NHLBI NIH HHS/United States ; N01-HB-37163/HB/NHLBI NIH HHS/United States ; N01-HB-37166/HB/NHLBI NIH HHS/United States ; N01-HB-37164/HB/NHLBI NIH HHS/United States ; N01HB37163/HL/NHLBI NIH HHS/United States ; }, mesh = {*Biological Products ; Blood Specimen Collection ; *Cell Survival ; Commerce ; *Cryopreservation ; Health Facilities ; Humans ; Quality Control ; }, abstract = {BACKGROUND AIMS: Shipment of therapeutic somatic cells between a current good manufacturing practice (cGMP) facility and a clinic or between different cGMP facilities requires validated standard operating procedures (SOP). Under National Heart Lung & Blood Institute (NHLBI) sponsorship, the Production Assistance for Cellular Therapies (PACT) group conducted a validation study for the shipping SOP it has created, including shipments of cryopreserved somatic cells, fresh peripheral blood specimens and apheresis products.

METHODS: Comparisons of pre- and post-shipped cells and cell products at the three participating facilities included measurements of viability, phenotypic profiles and cellular functions. The data were analyzed at the University of Pittsburgh Biostatistics Facility.

RESULTS: No consistent shipping effects on cell viability, phenotype or functions were detected for cryopreserved and shipped peripheral blood mononuclear cells (PBMC), monocytes, immature dendritic cells (iDC), NK-92 or cytotoxic T cells (CTL). Cryopreserved mesenchymal stromal cells (MSC) had a significantly decreased viability after shipment, but this effect was in part because of inter-laboratory variability in the viable cell counts. Shipments of fresh peripheral blood and apheresis products for the generation of CTL and dendritic cells (DC), respectively, had no significant effects on cell product quality. MSC were successfully generated from fresh bone marrow samples shipped overnight.

CONCLUSIONS: This validation study provides a useful set of data for guiding shipments of therapeutic somatic cells in multi-institutional clinical trials.}, } @article {pmid20733117, year = {2010}, author = {Li, CI and Chlebowski, RT and Freiberg, M and Johnson, KC and Kuller, L and Lane, D and Lessin, L and O'Sullivan, MJ and Wactawski-Wende, J and Yasmeen, S and Prentice, R}, title = {Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women's health initiative observational study.}, journal = {Journal of the National Cancer Institute}, volume = {102}, number = {18}, pages = {1422-1431}, pmid = {20733117}, issn = {1460-2105}, support = {N01WH22110/WH/WHI NIH HHS/United States ; N01WH42129-32/WH/WHI NIH HHS/United States ; N01WH32100-2/WH/WHI NIH HHS/United States ; N01WH32108-9/WH/WHI NIH HHS/United States ; N01WH42107-26/WH/WHI NIH HHS/United States ; N01WH32122/WH/WHI NIH HHS/United States ; N01WH32105-6/WH/WHI NIH HHS/United States ; N01WH32111-13/WH/WHI NIH HHS/United States ; N01WH32118-32119/WH/WHI NIH HHS/United States ; N01WH32115/WH/WHI NIH HHS/United States ; N01WH44221/WH/WHI NIH HHS/United States ; N01WH24152/WH/WHI NIH HHS/United States ; }, mesh = {Aged ; Alcohol Drinking/*adverse effects ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*epidemiology/etiology ; Carcinoma, Ductal, Breast/chemistry/*epidemiology/etiology ; Carcinoma, Lobular/chemistry/*epidemiology/etiology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasms, Hormone-Dependent/chemistry/*epidemiology/etiology ; Observation ; Odds Ratio ; *Postmenopause ; Proportional Hazards Models ; Prospective Studies ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Risk Factors ; United States/epidemiology ; *Women's Health ; }, abstract = {BACKGROUND: Alcohol consumption is a well-established risk factor for breast cancer. This association is thought to be largely hormonally driven, so alcohol use may be more strongly associated with hormonally sensitive breast cancers. Few studies have evaluated how alcohol-related risk varies by breast cancer subtype.

METHODS: We assessed the relationship between self-reported alcohol consumption and postmenopausal breast cancer risk among 87 724 women in the Women's Health Initiative Observational Study prospective cohort from 1993 through 1998. Multivariable adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.

RESULTS: A total of 2944 invasive breast cancer patients were diagnosed during follow-up through September 15, 2005. In multivariable adjusted analyses, alcohol consumption was positively related to risk of invasive breast cancer overall, invasive lobular carcinoma, and hormone receptor-positive tumors (all P(trend) ≤ .022). However, alcohol consumption was more strongly related to risk of certain types of invasive breast cancer compared with others. Compared with never drinkers, women who consumed seven or more alcoholic beverages per week had an almost twofold increased risk of hormone receptor-positive invasive lobular carcinoma (HR = 1.82; 95% CI = 1.18 to 2.81) but not a statistically significant increased risk of hormone receptor-positive invasive ductal carcinoma (HR = 1.14; 95% CI = 0.87 to 1.50; difference in HRs per drink per day among current drinkers = 1.15; 95% CI = 1.01 to 1.32, P = .042). The absolute rates of hormone receptor-positive lobular cancer among never drinkers and current drinkers were, 5.2 and 8.5 per 10 000 person-years, respectively, whereas for hormne receptor-positive ductal cancer they were 15.2 and 17.9 per 10 000 person-years, respectively.

CONCLUSIONS: Alcohol use may be more strongly associated with risk of hormone-sensitive breast cancers than hormone-insensitive subtypes, suggesting distinct etiologic pathways for these two breast cancer subtypes.}, } @article {pmid20731838, year = {2010}, author = {Shishido-Hara, Y and Kurata, A and Fujiwara, M and Itoh, H and Imoto, S and Kamma, H}, title = {Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?.}, journal = {Diagnostic pathology}, volume = {5}, number = {}, pages = {55}, pmid = {20731838}, issn = {1746-1596}, mesh = {Adult ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy ; Breast Neoplasms/blood supply/chemistry/immunology/*pathology/surgery ; Carcinoma, Ductal, Breast/blood supply/chemistry/immunology/*pathology/surgery ; Carcinoma, Giant Cell/blood supply/chemistry/immunology/*pathology/surgery ; Carcinosarcoma/blood supply/chemistry/immunology/*pathology/surgery ; *Cell Transdifferentiation ; Female ; Humans ; Immunohistochemistry ; Macrophages/chemistry/immunology/*pathology ; Mastectomy ; Microvessels/pathology ; Neoplasm Staging ; Osteoclasts/chemistry/immunology/*pathology ; Tumor Microenvironment ; }, abstract = {Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.}, } @article {pmid20726405, year = {2010}, author = {Seidman, GI}, title = {Is a flat-line a good thing? On the privatization of Israel's healthcare system.}, journal = {American journal of law & medicine}, volume = {36}, number = {2-3}, pages = {452-481}, doi = {10.1177/009885881003600209}, pmid = {20726405}, issn = {0098-8588}, mesh = {Delivery of Health Care/*organization & administration ; Financing, Government ; Health Expenditures ; Health Policy ; Humans ; Israel ; *Privatization/legislation & jurisprudence ; Quality of Health Care ; Social Welfare ; }, abstract = {Israel presents an intriguing conundrum: on the one hand, it provides quality healthcare in a near-universal healthcare system; on the other, it has maintained healthcare costs level at approximately 7.7% of GDP. This comes at a time when all western nations struggle with one or both sides of the equation: how to offer affordable, good quality health care to the population while curbing the sharp rise in health related costs. This paper explains both how Israel has achieved this 'flat line" effect and the social and political costs of this achievement.}, } @article {pmid20716161, year = {2010}, author = {Yu, L and Yang, W and Cai, X and Shi, D and Fan, Y and Lu, H}, title = {Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosis.}, journal = {Histopathology}, volume = {57}, number = {2}, pages = {193-201}, doi = {10.1111/j.1365-2559.2010.03601.x}, pmid = {20716161}, issn = {1365-2559}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; ErbB Receptors/metabolism ; Female ; Humans ; Immunohistochemistry ; Keratins/metabolism ; Middle Aged ; Necrosis ; Neoplasms, Hormone-Dependent/metabolism/pathology ; Phenotype ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Trans-Activators/metabolism ; Transcription Factors ; Tumor Suppressor Proteins/metabolism ; Vimentin/metabolism ; }, abstract = {AIMS: To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal-like phenotype and its prognosis.

METHODS AND RESULTS: The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohistochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high-molecular-weight CK (34betaE12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring-like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal-like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal-like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal-like markers. Follow-up data of 19 patients were available. Median progression-free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months).

CONCLUSIONS: CNC has distinctive morphological features, which mostly exhibit a basal-like immunophenotype and poor prognosis. CNC is a typical representative of basal-like breast cancer.}, } @article {pmid20715656, year = {2010}, author = {El-Daly, H and Gudi, M}, title = {Evaluation of nipple discharge cytology and diagnostic value of red blood cells in cases with negative cytology: a cytohistologic correlation.}, journal = {Acta cytologica}, volume = {54}, number = {4}, pages = {560-562}, doi = {10.1159/000325177}, pmid = {20715656}, issn = {0001-5547}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis ; Carcinoma in Situ/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Cytodiagnosis/methods ; Erythrocytes/*pathology ; Exudates and Transudates/*cytology/metabolism ; Female ; Humans ; Middle Aged ; Nipples/metabolism/*pathology ; Predictive Value of Tests ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the sensitivity and specificity of nipple discharge cytology and to determine the diagnostic value of the presence of red blood cells (RBCs) in cases with negative cytology.

STUDY DESIGN: Samples were received either as air-dried or alcohol-fixed slides. All cytology cases were reported by cytopathologists in the Hammersmith Pathology Department.

RESULTS: We identified 98 consecutive female patients with nipple discharge cytology in the Hammersmith and Charing Cross hospitals during the period of May 2007 to May 2009. The cytodiagnoses were as follows: 86 cases had negative cytology, 9 cases were C3 (atypia but likely benign), and 3 cases were suspicious for or consistent with malignancy. Thirty of these cases had subsequent biopsy and showed: 9 benign cases, 3 cases with atypical papilloma and 3 cases with a malignant diagnosis (in situ and/or invasive ductal carcinoma). All suspicious and malignant cases with available macroscopic description (whether positive or negative on nipple discharge cytology) were blood stained and on microscopy contained RBCs.

CONCLUSION: Nipple discharge cytology is a useful method in the diagnosis of malignant and suspicious cases. Further evaluation is needed to assess the value of the presence of RBCs in cases with negative cytology and its correlation with a subsequent diagnosis of malignancy.}, } @article {pmid20712900, year = {2010}, author = {Mao, XY and Fan, CF and Zheng, HC and Wei, J and Yao, F and Jin, F}, title = {p53 nuclear accumulation and ERalpha expression in ductal hyperplasia of breast in a cohort of 215 Chinese women.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {29}, number = {1}, pages = {112}, pmid = {20712900}, issn = {1756-9966}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/pathology ; Cell Nucleus/*chemistry ; Chi-Square Distribution ; China ; Cohort Studies ; Disease Progression ; Estrogen Receptor alpha/*analysis ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Middle Aged ; Precancerous Conditions/*chemistry/pathology ; Tumor Suppressor Protein p53/*analysis ; Young Adult ; }, abstract = {INTRODUCTION: Women with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years such as p53 and estrogen receptor alpha (ERalpha). However, p53 nuclear accumulation and ERalpha expression have not been assessed in ductal hyperplasia co-existing with ductal carcinoma in situ (DCIS) or IDC versus pure ductal hyperplasia without DCIS or IDC.

MATERIALS AND METHODS: We investigated p53 nuclear accumulation and ERalpha expression in breast ductal hyperplasia in a cohort of 215 Chinese women by immunohistochemistry (IHC), which included 129 cases of pure ductal hyperplasia, 86 cases of ductal hyperplasia co-existing with DCIS (41 cases) or IDC (45 cases).

RESULTS: Nuclear p53 accumulation was identified in 22.8% of ADH (31/136), 41.5% of DCIS (17/41) and 42.2% of IDC (19/45), and no case of UDH (0/79). No difference in nuclear p53 accumulation was observed between pure ADH and ADH co-existing with DCIS (ADH/DCIS) or IDC (ADH/IDC) (P>0.05). The positive rate of ERalpha expression was lower in ADH (118/136, 86.8%) than that in UDH (79/79, 100%) (P<0.001), but higher than that in DCIS (28/41, 68.3%) or IDC (26/45, 57.8%) respectively (P<0.001). The frequency of ERalpha expression was lower in ADH/DCIS (23/29, 79.31%) and ADH/IDC (23/30, 76.67%) than that in pure ADH (72/77, 93.51%) respectively (P<0.05). There was a negative weak correlation between p53 nuclear accumulation and ERalpha expression as for ADH (coefficient correlation -0.51; P<0.001).

CONCLUSIONS: Different pathological types of ductal hyperplasia of breast are accompanied by diversity in patterns of nuclear p53 accumulation and ERalpha expression. At least some pure ADH is molecularly distinct from ADH/CIS or ADH/IDC which indicated the two types of ADH are molecularly distinct entities although they have the same morphological appearance.}, } @article {pmid20704578, year = {2010}, author = {Tamaki, K and Sasano, H and Maruo, Y and Takahashi, Y and Miyashita, M and Moriya, T and Sato, Y and Hirakawa, H and Tamaki, N and Watanabe, M and Ishida, T and Ohuchi, N}, title = {Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast.}, journal = {Cancer science}, volume = {101}, number = {4}, pages = {1051-1058}, doi = {10.1111/j.1349-7006.2009.01483.x}, pmid = {20704578}, issn = {1349-7006}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/*pathology ; Cell Cycle Proteins/*metabolism ; Cell Nucleus/chemistry/genetics/metabolism ; Female ; Humans ; Neovascularization, Pathologic/genetics ; Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism ; Risk ; Vascular Endothelial Growth Factor A/genetics/metabolism ; }, abstract = {Vasohibin-1 is a recently identified negative feedback regulator of angiogenesis induced by VEGF-A and bFGF. In this study, we first evaluated mRNA expression of vasohibin-1 and CD31 in 39 Japanese female breast carcinoma specimens including 22 invasive ductal carcinoma (IDC) and 17 ductal carcinoma in situ (DCIS) using a real-time quantitative RT-PCR (QRT-PCR) with LightCycler system. In addition, we also immunolocalized vasohibin-1 and CD31 and compared their immunoreactivity to nuclear grades and histological grades of 100 carcinoma cases (50 IDC and 50 DCIS). There were no statistically significant differences of CD31 mRNA expression and the number of CD31 positive vessels between DCIS and IDC (P = 0.250 and P = 0.191, respectively), whereas there was a statistically significant difference in vasohibin-1 mRNA expression and the number of vasohibin-1 positive vessels in DCIS and IDC (P = 0.022 and P < or = 0.001, respectively). There was a significant positive correlation between vasohibin-1 mRNA level and Ki-67 labeling index in DCIS (r(2) = 0.293, P < or = 0.001). In addition, vasohibin-1 mRNA expression was correlated with high nuclear and histological grades in DCIS cases and a significant positive correlation was detected between the number of vasohibin-1 positive vessels and Ki-67 labeling index or nuclear grade or Van Nuys classification of carcinoma cells (P < or = 0.001, respectively). These results all indicate the possible correlation between aggressive biological features in DCIS including increased tumor cell proliferation and the status of neovascularization determined by vasohibin-1 immunoreactivity.}, } @article {pmid20703102, year = {2010}, author = {Yu, J and Ohuchida, K and Mizumoto, K and Fujita, H and Nakata, K and Tanaka, M}, title = {MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis, and involved in cancer cell proliferation and invasion.}, journal = {Cancer biology & therapy}, volume = {10}, number = {8}, pages = {748-757}, doi = {10.4161/cbt.10.8.13083}, pmid = {20703102}, issn = {1555-8576}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; *Cell Proliferation ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/pathology ; Paraffin Embedding ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Analysis ; Tissue Fixation ; }, abstract = {The microRNA-17-92 cluster is an oncogene in human B cell lymphomas and lung cancers. Previous microRNA microarray data revealed that miR-17-5p, a member of the miR-17-92 cluster, is upregulated in pancreatic cancer. However, the involvement of miR-17-5p expression in pancreatic carcinogenesis has not well been studied. In the present study, we measured the miR-17-5p expression levels in pancreatic cancer cell lines, primary cultures of normal human pancreatic ductal cells, formalin-fixed paraffin-embedded (FFPE) tissue samples derived from 80 patients who underwent pancreatectomy for pancreatic cancer and microdissected cells (including normal ductal epithelial, pancreatic intraepithelial neoplasia-1B and invasive ductal carcinoma cells) by qRT-PCR. Furthermore, we investigated the effects of upregulation of miR-17-5p expression on the proliferation and invasion of pancreatic cancer cells. We found that pancreatic cancer cells expressed higher levels of miR-17-5p than primary cultured normal ductal cells. miR-17-5p was also overexpressed in pancreatic cancer in FFPE and microdissected samples. Furthermore, analysis of macrodissected FFPE samples revealed that high miR-17-5p expression was associated with a poor prognosis (p = 0.03). In addition, in vitro experiments revealed that SUIT-2 and KP-2 pancreatic cancer cells transfected with the miR-17-5p precursor showed significantly higher cell growth ratios than the corresponding control cells (p < 0.001 and p = 0.012, respectively), as well as significantly higher numbers of invading cells (p < 0.0001 for both). The present findings suggest that miR-17-5p plays important roles in pancreatic carcinogenesis and cancer progression, and is associated with a poor prognosis in pancreatic cancer.}, } @article {pmid20701091, year = {2009}, author = {Gao, J and McNutt, MA and Yi, W and Chen, J and Gu, J}, title = {Quantitative morphometry by image analysis of normal, hyperplastic and cancerous ductal breasts.}, journal = {Analytical and quantitative cytology and histology}, volume = {31}, number = {5}, pages = {255-261}, pmid = {20701091}, mesh = {Breast/*cytology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Cell Nucleus/pathology ; Cell Proliferation ; Cytoplasm/pathology ; Female ; Humans ; Hyperplasia ; Image Processing, Computer-Assisted/*methods/statistics & numerical data ; Mammary Glands, Human/pathology ; Middle Aged ; }, abstract = {OBJECTIVE: To analyze a number of quantitative variables in ductal epithelial breast proliferations and test them against diagnoses established by standard histologic and cytologic criteria in order to determine which variables are useful in discriminating between histologic diagnoses.

STUDY DESIGN: A method was developed for the semiautomatic segmentation and quantitative analysis of breast ductal proliferations using image analysis. This permitted duct profiles and intraductal epithelial proliferations to be analyzed by computer, with calculation of a total of 17 variables--for example, nuclear/cytoplasmic ratio, nuclear circularity, average internuclear distance and lumen area. Four groups were analyzed employing a total of 80 cases with diagnoses established by standard histologic criteria, including normal breast duct (DN = 19 cases), ductal hyperplasia without atypia (DH = 21 cases), ductal carcinoma in situ (DCIS = 20 cases) and invasive ductal carcinoma (INV = 20 cases).

RESULTS: Of the 17 quantitative variables tested in this study, 15 showed statistically significant differences in values between DH and DCIS (p < 0.05), and 7 showed statistically significant differences between DN and DH (p < 0.05).

CONCLUSION: By quantitative morphometric analysis of selected variables, a significant statistical distinction can be made between diagnostic groups, paving the way for automatic computerized image recognition for differential diagnosis.}, } @article {pmid20701077, year = {2010}, author = {Nese, N and Kandiloglu, AR and Simsek, G and Lekili, M and Ozdamar, A and Catalkaya, A and Coskun, T}, title = {Comparison of the desmoplastic reaction and invading ability in invasive ductal carcinoma of the breast and prostatic adenocarcinoma based on the expression of heat shock protein 47 and fascin.}, journal = {Analytical and quantitative cytology and histology}, volume = {32}, number = {2}, pages = {90-101}, pmid = {20701077}, mesh = {Adenocarcinoma/metabolism/mortality/*secondary ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Carrier Proteins/*metabolism ; Female ; HSP47 Heat-Shock Proteins/*metabolism ; Humans ; Immunoenzyme Techniques ; Male ; Mastectomy ; Microfilament Proteins/*metabolism ; Middle Aged ; Neoplasm Staging ; Prostatectomy ; Prostatic Neoplasms/metabolism/mortality/*pathology ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the diversity within invasive ductal carcinoma (IDC) and prostatic adenocarcinoma (PCa) by evaluating immunohistochemical expression of heat shock protein 47 (HSP47) and fascin, the molecules that are related to desmoplasia and invasion, and analyze its correlation with clinicopathologic parameters.

STUDY DESIGN: HSP47 and fascin immunoreactivity (IR) was evaluated in 49 mastectomies diagnosed as IDC and 57 radical prostatectomies diagnosed as PCa. IR was evaluated as: 0: < 5%, 1+: 5-25%, 2+: 25-50%, 3+: > 50%.

RESULTS: HSP47 and fascin were localized to cytoplasm, and HSP47 and fascin IR were higher in IDC and PCa than benign groups (p < 0.05). HSP47 IR in neoplastic cells was 42.1% and 28.6%, in stroma was 81.6% and 15.8% in IDC and PCa, respectively; fascin IR in neoplastic cells was 65.3% in IDC and 15.8% in PCa. Fascin expression correlated with estrogen receptor and progesterone receptor negativity, tumor size and stage in IDC and surgical margin status in PCa. HSP47 expression correlated bilaterality in PCa. HSP47 positively correlated with survival in IDC.

CONCLUSION: HSP47 and fascin expression may play role in the pathogenesis of IDC and PCa because their expression is significantly higher in IDC and PCa than their normal counterpart. Although there is no relationship with recurrence or metastatic status, fascin overexpression correlated with tumor size, which may prompt its use as a prognostic factor in IDC.}, } @article {pmid20698136, year = {2010}, author = {Besser-Silconi, Z and Lozić, AA and Misljenović, N}, title = {Fine needle aspiration cytology of minimal breast cancer in Istria County.}, journal = {Collegium antropologicum}, volume = {34}, number = {2}, pages = {605-607}, pmid = {20698136}, issn = {0350-6134}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/methods ; Biopsy, Needle/*methods ; Breast Neoplasms/*pathology ; Croatia ; Female ; Humans ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {Breast cancer is the most frequent malignant tumour and leading cause of death in women aged 35 to 64 years in Istria County. The minimal invasive carcinoma and in situ carcinoma have a better prognosis so we try to find them during preventive exams. The aim of this study was to identify minimal breast cancers in fine needle aspiration biopsies of breast lesions made in Pula General Hospital between the years 2006 and 2008. There were 39 tumours with a maximal diameter of less than 10 mm in 1316 biopsies and 251 cytologically diagnosed breast cancers. In most cases, they were solitary, well differentiated neoplasms (48.7%). They were diagnosed in women aged 39 to 89 years and most frequently found in women aged 60 to 69 years. The most frequent histological type of operated minimal breast carcinomas was invasive ductal carcinoma. In that period, the minimal breast cancer percentage of all cytologically diagnosed breast cancers was 15.5% but in the first 6 months of 2009, the result was 48.7%.}, } @article {pmid20696144, year = {2010}, author = {Rashid, MH and Lopez-Garcia, JA and Cervero, F}, title = {Stimulation of dorsal root afferents increases the excitability of ascending sensory axons in the isolated spinal cord of mature mice.}, journal = {Brain research}, volume = {1356}, number = {}, pages = {24-31}, doi = {10.1016/j.brainres.2010.08.001}, pmid = {20696144}, issn = {1872-6240}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Afferent Pathways/drug effects/*physiology ; Animals ; Axons/drug effects/*physiology ; Electric Stimulation/methods ; Female ; Mice ; Mice, Inbred C57BL ; Organ Culture Techniques ; Sensory Receptor Cells/drug effects/*physiology ; Spinal Cord/drug effects/*physiology ; Spinal Nerve Roots/*physiology ; }, abstract = {The phenomenon of windup has often been used to assess excitability increases of spinal neurons induced by repetitive stimulation of nociceptive afferents. Windup has been studied in individual spinal cord neurons and in spinal motor reflexes neither of which accurately reflect the forward transmission of nociceptive signals to the brain. In addition, most in vitro studies of spinal windup have been conducted on immature or juvenile animals and it is challenging to extrapolate these results to the adult spinal cord. In the present study, we have used an in vitro whole spinal cord preparation from functionally mature mice (up to 8 weeks old) to record windup activity in ascending axons in the mid-thoracic region evoked by electrical stimulation of a lumbar or sacral dorsal root. Windup responses were observed in axons in the ipsi- and contralateral dorsolateral funiculus (iDLF and cDLF) and in the contralateral ventrolateral funiculus (cVLF). No windup responses were evoked in postsynaptic axons of the ipsilateral dorsal columns (iDC) and no postsynaptic responses were elicited in the ipsilateral ventrolateral funiculus (iVLF) or contralateral dorsal columns (cDC). Between 40% and 45% of all axons in the DLF and cVLF that responded to a single dorsal root stimulus also showed windup. The NMDA receptor antagonist MK-801 reversibly blocked such windup responses. These results illustrate that windup can be consistently recorded from ascending pathways in the mature spinal cord in vitro but also show that windup can only be elicited in a proportion of sensory axons projecting through some, but not all, ascending spinal cord pathways.}, } @article {pmid20688766, year = {2011}, author = {Meluzin, J and Spinarova, L and Hude, P and Krejci, J and Podrouzkova, H and Pesl, M and Orban, M and Dusek, L and Jarkovsky, J and Korinek, J}, title = {Estimation of left ventricular filling pressures by speckle tracking echocardiography in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology}, volume = {12}, number = {1}, pages = {11-18}, doi = {10.1093/ejechocard/jeq088}, pmid = {20688766}, issn = {1532-2114}, mesh = {Adult ; Aged ; Cardiac Catheterization ; Cardiomyopathy, Dilated/*diagnostic imaging/*physiopathology ; Case-Control Studies ; Chi-Square Distribution ; Diastole ; *Echocardiography, Doppler, Pulsed ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve/physiopathology ; Prospective Studies ; Pulmonary Wedge Pressure ; ROC Curve ; *Ventricular Pressure ; }, abstract = {AIMS: the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (E(a)) is frequently used to predict an increase in left ventricular filling pressure (LVFP). However, this approach has several limitations. The aim of this study was to test whether additional information is gained by new echocardiographic indexes utilizing strain and strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D-STE) for the estimation of LVFP.

METHODS AND RESULTS: fifty-one patients with idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler echocardiography and 2D-STE performed simultaneously with right heart catheterization. Receiver operating characteristic analysis showed that circumferential strain and the SR during late diastolic LV filling (0.956 and 0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911, P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg.

CONCLUSION: when compared with the E/E(a) ratio, several 2D-STE-derived parameters better estimated the increase in LVFP in patients with IDC.}, } @article {pmid20682973, year = {2010}, author = {Cho, YH and Yazici, H and Wu, HC and Terry, MB and Gonzalez, K and Qu, M and Dalay, N and Santella, RM}, title = {Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients.}, journal = {Anticancer research}, volume = {30}, number = {7}, pages = {2489-2496}, pmid = {20682973}, issn = {1791-7530}, support = {P30 CA013696/CA/NCI NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; ES009089/ES/NIEHS NIH HHS/United States ; CA013696/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*blood/*genetics ; Breast Neoplasms/*blood/*genetics ; Case-Control Studies ; *DNA Methylation ; DNA, Neoplasm/*blood/genetics ; Female ; Humans ; Leukocytes/chemistry/physiology ; Middle Aged ; Promoter Regions, Genetic ; }, abstract = {BACKGROUND: Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. Detection of aberrant methylation in white blood cells (WBC) has been suggested as a marker for cancer development, but has not been extensively investigated. This study was carried out to determine whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for breast cancer risk.

PATIENTS AND METHODS: Promoter hypermethylation of 8 tumor suppressor genes (RASSF1A, APC, HIN1, BRCA1, CYCLIND2, RARbeta, CDH1 and TWIST1) and DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients by the MethyLight assay. Methylation in WBC from 40 controls was also analyzed.

RESULTS: Tumor and adjacent tissues showed frequent hypermethylation for all genes tested, while WBC DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1, there was agreement between hypermethylation in tumor and adjacent tissues (p=0.04, p=0.02, p=0.005 and p<0.0001, respectively). DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant correlations in the methylation of Sat2M1 between tumor and adjacent tissues and WBC DNA were found (p<0.0001 and p=0.046, respectively). There was also a significant difference in methylation of Sat2M1 between cases and controls (p=0.01).

CONCLUSION: These results suggest that further studies of WBC methylation, including prospective studies, may provide biomarkers of breast cancer risk.}, } @article {pmid20676743, year = {2011}, author = {Lecarpentier, E and Ouaffi, L and Mir, O and Berveiller, P and Maurel, M and Pujade-Lauraine, E and Bouillot, JL and Veyrie, N}, title = {Bevacizumab-induced small bowel perforation in a patient with breast cancer without intraabdominal metastases.}, journal = {Investigational new drugs}, volume = {29}, number = {6}, pages = {1500-1503}, pmid = {20676743}, issn = {1573-0646}, mesh = {Angiogenesis Inhibitors/*adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Bevacizumab ; Breast Neoplasms/*drug therapy/pathology/therapy ; Carcinoma, Ductal, Breast/drug therapy/pathology/therapy ; Female ; Humans ; Intestinal Perforation/*chemically induced ; Intestine, Small/injuries ; Middle Aged ; Peritonitis/diagnosis/etiology ; }, abstract = {A 53-years-old woman presented with sudden abdominal pain. One year before, she was diagnosed an inflammatory ductal carcinoma of the left breast (T3N0M0) and received 6 cycles of epirubicin and cyclophosphamide followed by 9 cycles of paclitaxel. A radical left mastectomy with lymphadenectomy was performed. On histopathology, the invasive ductal carcinoma was poorly differentiated, histological grade III without lymphovascular emboli, expressing E-cadherin, with negative hormone receptors status and no HER-2 overexpression. The final staging after chemotherapy was pT3N1M0, necessitating an adjuvant radiotherapy. Four months postoperatively, a CT-scan revealed liver and lung metastases and chemotherapy combining gemcitabine, oxaliplatin and bevacizumab was started for 13 days when she suddenly developed severe abdominal pain. A CT-scan showed a pneumoperitoneum. She had a median laparotomy confirming the diagnosis of peritonitis by digestive perforation without ovarian, uterine, lymphatic, or peritoneal carcinomatosis. Assessment of the totality of the gastrointestinal tract showed two distinct punched out perforations of the small bowel, without macroscopic signs of tumor or metastases: one on the jejunum at 50 cm from the Treitz and the second at 10 cm of the end of the ileum. Small bowel resection with jejunojejunostomy and a lateral ileostomy were performed. Regarding the macroscopical pathological findings, the mucosa showed an ulceration measuring of 1 cm without tumor. On microscopy we found a tranparietal neoplastic infiltration. Vessels were morphologically normal with tumoral cells' morphology and architecture identical to the primary breast carcinoma. Chemotherapy was not reintroduced after surgery and the patient died on the 57th postoperative day.}, } @article {pmid20672290, year = {2011}, author = {Liu, KJ and Lee, YL and Yang, YY and Shih, NY and Ho, CC and Wu, YC and Huang, TS and Huang, MC and Liu, HC and Shen, WW and Leu, SJ}, title = {Modulation of the development of human monocyte-derived dendritic cells by lithium chloride.}, journal = {Journal of cellular physiology}, volume = {226}, number = {2}, pages = {424-433}, doi = {10.1002/jcp.22348}, pmid = {20672290}, issn = {1097-4652}, mesh = {Adjuvants, Immunologic/pharmacology ; Animals ; Antigens, CD/immunology ; B7-2 Antigen/immunology ; Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/cytology/*drug effects/*physiology ; Enzyme Inhibitors/metabolism ; Glycogen Synthase Kinase 3/immunology ; Glycogen Synthase Kinase 3 beta ; Humans ; Immunoglobulins/immunology ; Interleukins/immunology ; Lithium Chloride/*pharmacology ; Membrane Glycoproteins/immunology ; Mitogen-Activated Protein Kinase Kinases/immunology ; Monocytes/cytology/*drug effects/*physiology ; PPAR gamma/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune responses, this study investigated the influence of lithium chloride (LiCl) on the development and function of DC. Exposure to LiCl during the differentiation of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression and increases the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α. However, the presence of LiCl during LPS-induced maturation of iDC has the opposite effect. During iDC differentiation, LiCl suppresses the activity of glycogen synthase kinase (GSK)-3β, and activates PI3K and MEK. In addition, LiCl activates peroxisome proliferator-activated receptor γ (PPARγ) during iDC differentiation, a pathway not described before. Each of these signaling pathways appears to have distinct impact on the differentiating iDC. The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3β pathway. LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT, and PPARγ pathways, while the increased production of IL-1β and TNF-α mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10 secretion in iDC is mediated through inhibition of GSK-3β. We have also demonstrated that PPARγ is downstream of GSK-3β and is responsible for the LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10 secretion. The combined influence of these molecular signaling pathways may account for certain clinical effect of lithium.}, } @article {pmid20667129, year = {2010}, author = {Gunn, S and Yeh, IT and Lytvak, I and Tirtorahardjo, B and Dzidic, N and Zadeh, S and Kim, J and McCaskill, C and Lim, L and Gorre, M and Mohammed, M}, title = {Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {396}, pmid = {20667129}, issn = {1471-2407}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human, Pair 17/*genetics ; Comparative Genomic Hybridization ; Female ; *Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; *Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods.

METHODS: In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms.

RESULTS: Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability.

CONCLUSIONS: These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two probe FISH interphase analysis is inadequate and results interpreted using the HER2/CEP17 ratio should be reported "with caution" when the presence of centromeric amplification or monosomy is suspected by FISH signal gains or losses. The presence of these pericentromeric copy number changes may result in artificial skewing of the HER2/CEP17 ratio towards false negative or false positive results in breast cancer with chromosome 17 complexity. Full genomic analysis should be considered in all cases with complex chromosome 17 aneusomy as these cases are likely to have genome-wide instability, amplifications, and a poor prognosis.}, } @article {pmid20665210, year = {2010}, author = {Raeisi, E and Firoozabadi, SM and Hajizadeh, S and Rajabi, H and Hassan, ZM}, title = {The effect of high-frequency electric pulses on tumor blood flow in vivo.}, journal = {The Journal of membrane biology}, volume = {236}, number = {1}, pages = {163-166}, pmid = {20665210}, issn = {1432-1424}, mesh = {Animals ; Carcinoma, Ductal, Breast/*blood supply/therapy ; *Electroporation ; Female ; Laser-Doppler Flowmetry/methods ; Mammary Neoplasms, Experimental/*blood supply/therapy ; Mice ; Mice, Inbred BALB C ; Time Factors ; }, abstract = {The aim of this study was to evaluate the effect of a 5-kHz repetition frequency of electroporating electric pulses in comparison to the standard 1-Hz frequency on blood flow of invasive ductal carcinoma tumors in Balb/C mice. Electroporation was performed by the delivery of eight electric pulses of 1,000 V cm(-1) and 100 mus duration at a repetition frequency of 1 Hz or 5 kHz. Blood flow changes in tumors were measured by laser Doppler flowmetry. Monitoring was performed continuously for 10 min before application of the electric pulses as well as immediately after application of the electric pulses for 40 min. The delivery of electric pulses to tumors induced changes in tumor blood flow. The reduction in blood flow started after the stimulation and continued for the 40-min period of observation. There was a significant difference in blood flow changes 3 min after application of the electric pulses at 1-Hz or 5-kHz repetition frequency. However, after 3 min the difference became nonsignificant. The findings showed that the high pulse frequency (5 kHz) had an effect comparable to the 1-Hz frequency on tumor blood flow except at very short times after pulse delivery, when pulses at 5 kHz produced a more intense reduction of blood flow.}, } @article {pmid20663721, year = {2010}, author = {Muggerud, AA and Hallett, M and Johnsen, H and Kleivi, K and Zhou, W and Tahmasebpoor, S and Amini, RM and Botling, J and Børresen-Dale, AL and Sørlie, T and Wärnberg, F}, title = {Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer.}, journal = {Molecular oncology}, volume = {4}, number = {4}, pages = {357-368}, pmid = {20663721}, issn = {1878-0261}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; Cluster Analysis ; Comparative Genomic Hybridization ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Microarray Analysis ; Middle Aged ; Multigene Family ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the "intrinsic" molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients.}, } @article {pmid20661826, year = {2010}, author = {Dave, B and Wynne, R and Su, Y and Korourian, S and Chang, JC and Simmen, RC}, title = {Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats.}, journal = {Nutrition and cancer}, volume = {62}, number = {6}, pages = {774-782}, doi = {10.1080/01635581.2010.494334}, pmid = {20661826}, issn = {1532-7914}, mesh = {Animals ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Cell Line, Tumor ; Disease Progression ; Female ; Genistein/*administration & dosage ; Humans ; Hyaluronan Receptors/genetics ; Isoflavones/*administration & dosage ; Mammary Glands, Animal/chemistry ; Mammary Neoplasms, Experimental/chemistry/*etiology ; Rats ; Receptors, Progesterone/analysis/*physiology ; Transforming Growth Factor beta1/genetics ; }, abstract = {Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-methyl-N-nitrosourea, dietary intake of soy protein isolate (SPI) reduced mammary tumor occurrence but increased incidence of more invasive tumors in tumored rats, relative to the control diet casein. Here we evaluated whether mammary tumor progression in tumor-bearing rats lifetime exposed to SPI is associated with deregulated progesterone receptor (PR) isoform expression. In histologically normal mammary glands of rats with invasive ductal carcinoma lesions, PR-A protein levels were higher for SPI- than casein-fed rats, whereas PR-B was undetectable for both groups. Increased mammary PR-A expression was associated with higher transforming growth factor-beta1, stanniocalcin-1, and CD44 transcript levels; lower E-cadherin and estrogen receptor-alpha expression; and reduced apoptotic status in ductal epithelium. Serum progesterone (ng/ml) (CAS: 25.94 +/- 3.81; SPI: 13.19 +/- 2.32) and estradiol (pg/ml) (CAS: 27.9 +/- 4.49; SPI: 68.48 +/- 23.87) levels differed with diet. However, sera from rats of both diet groups displayed comparable mammosphere-forming efficiency in human MCF-7 cells. Thus, soy-rich diets may influence the development of more aggressive tumors by enhancing PR-A-dependent signaling in premalignant breast tissues.}, } @article {pmid20657229, year = {2010}, author = {Dietzel, M and Baltzer, PA and Vag, T and Gröschel, T and Gajda, M and Camara, O and Kaiser, WA}, title = {Magnetic resonance mammography of invasive lobular versus ductal carcinoma: systematic comparison of 811 patients reveals high diagnostic accuracy irrespective of typing.}, journal = {Journal of computer assisted tomography}, volume = {34}, number = {4}, pages = {587-595}, doi = {10.1097/RCT.0b013e3181db9f0e}, pmid = {20657229}, issn = {1532-3145}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Carcinoma, Lobular/*pathology ; Contrast Media ; Diagnosis, Differential ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Image Processing, Computer-Assisted/methods ; Magnetic Resonance Imaging/*methods ; Mammography/methods ; Middle Aged ; Observer Variation ; Reproducibility of Results ; Young Adult ; }, abstract = {OBJECTIVE: Invasive lobular (ILC) and ductal carcinomas (IDC) are the most frequent subtypes of breast cancer. Diagnosis of ILC is often challenging. This study was conducted to (1) evaluate dynamic and morphologic profiles and to (2) compare the diagnostic accuracy of IDC and ILC in magnetic resonance mammography (MRM).

METHODS: Our database consisted of all consecutive MRMs over a 12-year period (standardized protocol: T1-weighted fast low-angle shot; 0.1-mmol gadolinium-diethylenetriaminepentaacetate per kilogram of body weight; T2-weighted turbo spin-echo, 1.5 T; histological verification after MRM), which were evaluated by experienced (>500 MRMs) radiologists in consensus, applying 17 predefined descriptors. All the patients gave written consent; this study was approved by the local institutional review board. Extracting all the ILCs (n = 108), IDCs (n = 347), and benign lesions (n = 436) from the database, the data set of the study was created.In ILC and IDC diagnostic accuracy of single descriptors was calculated and compared separately (chi test). Using all the descriptors, a combined binary logistic regression analysis was applied to calculate the overall diagnostic accuracy for ILC and IDC. The corresponding areas under the curve were compared.

RESULTS: ILC and IDC, showed wash-in and an irregular shape without difference (P = 1.0 and P = 0.4). Wash-out was more typical of IDC (72.6%; ILC, 57.4%; P = 0.007). Perifocal edema was diagnosed more frequently in IDC (45.5%; P = 0.05). For overall accuracy, the areas under the curve were 0.929 for ILC and 0.939 for IDC (P = 0.5).

CONCLUSIONS: The dynamic and morphologic profiles of ILC and IDC were overlapping, and minor differences between both subgroups could be identified. Accordingly, the overall diagnostic accuracy of MRM was high and without difference between both subtypes of breast cancer.}, } @article {pmid20650763, year = {2010}, author = {Zhen, LF and Ye, CS and Liu, MF and Ding, GP and Liao, JJ}, title = {[Expressions of D2-40 and CD34 in invasive ductal carcinoma of the breast and the clinical implications].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {30}, number = {7}, pages = {1548-1551}, pmid = {20650763}, issn = {1673-4254}, mesh = {Adult ; Aged ; Antigens, CD34/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Lymphatic Vessels ; Microvessels ; Middle Aged ; Neoplasm Staging ; Prognosis ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the expression of D2-40 and CD34 in invasive ductal carcinoma of the breast and the clinical significance.

METHODS: D2-40 and CD34 expressions were detected immunohistochemically in 108 cases of invasive ductal carcinoma of the breast and 30 cases of breast fibroadenoma. The lymphatic microvessel density (LMD) and the microvessel density (MD), marked by D2-40 and CD34, respectively, were calculated and their relationship with the clinicopathological factors was analyzed.

RESULTS: The LMD and MD for invasive ductal carcinoma of the breast were significantly higher than those of breast fibroadenoma (P<0.01). One-way ANOVA indicated that the LMD differed significantly between tumors of different histological grades, status of lymph node metastasis and TNM stages; the MD also varied significantly with the tumor size, histological grade, lymph node metastasis and TNM stage. The LMD and MD showed a positive correlation to the tumor size (r=0.335, 0.337), histological grade (r=0.580, 0.671), lymph node metastasis (r=0.690, 0.721) and TNM stage (r=0.623, 0.634), but not to ER, PR or Her-2 status (P>0.05).

CONCLUSIONS: D2-40 can specifically mark the lymphatic endothelial cells in invasive ductal carcinoma of the breast. The LMD and MD are positively correlated to the clinicopathological factors of the malignancy. D2-40 and CD34 has the potential for use as the predictors to evaluate the tumor progression and metastasis.}, } @article {pmid20649064, year = {2010}, author = {Wiratkapun, C and Bunyapaiboonsri, W and Wibulpolprasert, B and Lertsithichai, P}, title = {Biopsy rate and positive predictive value for breast cancer in BI-RADS category 4 breast lesions.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {93}, number = {7}, pages = {830-837}, pmid = {20649064}, issn = {0125-2208}, mesh = {Adult ; Age Factors ; Biopsy/statistics & numerical data ; Breast/pathology ; Breast Neoplasms/classification/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/classification/*diagnostic imaging/pathology ; Female ; Humans ; Logistic Models ; Mammography/*statistics & numerical data ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Ultrasonography, Mammary/*statistics & numerical data ; }, abstract = {OBJECTIVE: To examine the biopsy rate and positive predictive value (PPV) for breast cancer in lesions categorized as BI-RADS (Breast Imaging reporting and Data System) category 4.

MATERIAL AND METHOD: The medical records of patients with BIRADS 4 breast lesion diagnosed at the breast diagnostic center Ramathibodi Hospital between December 1, 2004 and December 31, 2005 were retrospectively reviewed. PPV was calculated for patients who had biopsy performed or had clinical follow-up for at least two years. The radiographic and pathological findings were compared.

RESULTS: The biopsy rate of 536 lesions categorized as BI-RADS 4 was 75% (403 of 536). Malignancy was found in 95 of 460 patients; or a PPV of 21%, PPVs for subcategories 4A, 4B and 4C, were 9%, 21% and 57%, respectively. The most common malignancy was invasive ductal carcinoma (67%). Patients with advanced age, having a clinically palpable breast mass of large size, with mammographic findings of architectural distortion and asymmetrical density were significantly associated with a higher risk of breast cancer.

CONCLUSION: PPV for malignancy in the present study was comparable to previous studies. In subcategories 4B and 4C, the malignancy rate was higher than that in subcategory 4A.}, } @article {pmid20646630, year = {2010}, author = {Liu, N and Niu, Y and Wang, SL and Yu, Q and Zhang, RJ and Liu, TJ}, title = {[Diagnostic and prognostic significance of FOXA1 expression in molecular subtypes of breast invasive ductal carcinomas].}, journal = {Zhonghua yi xue za zhi}, volume = {90}, number = {20}, pages = {1403-1407}, pmid = {20646630}, issn = {0376-2491}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/*pathology ; Female ; Hepatocyte Nuclear Factor 3-alpha/*metabolism ; Humans ; Middle Aged ; Prognosis ; Protein Isoforms ; }, abstract = {OBJECTIVE: To investigate the expression of FOXA1 in breast invasive ductal carcinomas, observe its expression in all molecular subtypes of breast invasive ductal carcinomas and understand its diagnostic and prognostic significance.

METHODS: Tissue specimens were obtained from 213 cases of breast invasive ductal carcinoma (IDC) and their expressions of FOXA1 and Ki67 detected by immunohistochemistry. And the expressions of CK5/6 and CK14 were detected to distinguish between normal breast-like subtype and basal-like subtype.

RESULTS: The expression of FOXA1 was observed in 150 cases (70.4%). It correlated positively with ER and PR. But there was a negative correlation with histological grade, Nottingham prognostic index, p53 and Ki67. The expression of FOXA1 had difference between luminal and non-luminal subtypes. In luminal subtype, the expression of FOXA1 was associated with histological grade, PR, NPI, Ki67 and A subtype. In terms of prognosis, the expression of FOXA1 predicted a long disease-free survival and overall survival.

CONCLUSION: The expression of FOXA1 is associated with a good prognosis. FOXA1 is a promising candidate for clinical identification of luminal A subtype. Prognostic analysis of FOXA1 in low-risk breast cancers may prove to be useful in clinical treatment decision-making.}, } @article {pmid20645234, year = {2010}, author = {Seifert, L and Komar, J and Leprêtre, PM and Lemaitre, F and Chavallard, F and Alberty, M and Houel, N and Hausswirth, C and Chollet, D and Hellard, P}, title = {Swim specialty affects energy cost and motor organization.}, journal = {International journal of sports medicine}, volume = {31}, number = {9}, pages = {624-630}, doi = {10.1055/s-0030-1255066}, pmid = {20645234}, issn = {1439-3964}, mesh = {Adolescent ; Adult ; Arm/physiology ; Athletes ; Athletic Performance/*physiology ; Biomechanical Phenomena ; Energy Metabolism/physiology ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption/physiology ; Swimming/*physiology ; Videotape Recording ; Young Adult ; }, abstract = {The purpose of this study was to analyse the effect of swimmer specialty on energy cost and motor organization. The stroking parameters (velocity, stroke rate, stroke length, stroke index) and the index of coordination (IdC) of 6 elite sprinters were compared with those of 6 elite long-distance swimmers during an incremental swimming exercise test (6x300 m separated by 30 s of passive recovery) that progressively increased the energy cost. Energy cost (C), with its aerobic (Caero) and anaerobic (Canaero) components, was determined by measuring oxygen uptake (VO2) and blood lactate ([La]). Motor organization was assessed by analysis of video recordings from aerial and underwater side-view cameras. The results showed that throughout the test, both groups increased C, Canaero, stroke rate and IdC and decreased Caero and stroke length (all P<0.05). On the mean of the 300-m sets, sprinters had higher values for C (14.8 VS. 12.9 J x kg (-1).m (-1)), Canaero (33.8 VS. 23.4%), [La] (5.9 VS. 3.1 mmol x L (-1)), stroke length (2.31 VS. 2.28 m) and IdC (-11.2 VS. -21.7%) and lower values for Caero (66.2 VS. 79.6%), VO2 net (2 825 VS. 2 903 mL x min (-1)), stroke rate (0.55 VS. 0.62 Hz) and stroke index (2.96 VS. 3.19 m (2) x s (-1)) than long-distance swimmers (all P<0.05). For the same relative intensity, sprinters accumulated more lactate and swam more slowly than long-distance swimmers; they showed greater change in their arm coordination but their swimming economy was lower.}, } @article {pmid20636789, year = {2010}, author = {Flucke, U and Flucke, MT and Hoy, L and Breuer, E and Goebbels, R and Rhiem, K and Schmutzler, R and Winzenried, H and Braun, M and Steiner, S and Buettner, R and Gevensleben, H}, title = {Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach.}, journal = {Histopathology}, volume = {56}, number = {7}, pages = {852-859}, doi = {10.1111/j.1365-2559.2010.03555.x}, pmid = {20636789}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Medullary/metabolism/*pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; }, abstract = {AIMS: Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs.

METHODS AND RESULTS: Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2 alpha, AP-2 gamma). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2 alpha and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2 alpha: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05).

CONCLUSIONS: Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2 alpha overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs.}, } @article {pmid20634005, year = {2010}, author = {Xie, F and Wang, Q and Chen, Y and Gu, Y and Mao, H and Zeng, W and Zhang, X}, title = {Costimulatory molecule OX40/OX40L expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.}, journal = {Pathology, research and practice}, volume = {206}, number = {11}, pages = {735-739}, doi = {10.1016/j.prp.2010.05.016}, pmid = {20634005}, issn = {1618-0631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology/surgery ; Female ; Fibroadenoma/metabolism/pathology/surgery ; Fluorescent Antibody Technique, Direct ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Middle Aged ; OX40 Ligand/*metabolism ; Receptors, OX40/*metabolism ; Receptors, Progesterone/metabolism ; Young Adult ; }, abstract = {OX40, a membrane-bound member of the tumor-necrosis-factor-receptor (TNFR) superfamily, plays an important role in proliferation, survival and infiltration of activated T cells via binding to OX40L. Recent studies indicate that OX40/OX40L system mediates the adhesion and infiltration of adult T cell leukemia (ATL). Previously, we detected OX40 expression in breast carcinoma cell lines and tissues. The correlation of expression of OX40 and OX40L and clinical features in breast carcinogenesis, however, has not been well characterized. The expression of OX40 and OX40L in 107 invasive ductal carcinomas (IDCa), 9 ductal carcinomas in situ (DCIS), and 31 fibroadenomas from breast tissues and its relationship with the clinical features were determined using immunohistochemistry (peroxidase-conjugated polymer method, ChemMate™ Envision™ Detection kit). The positive immunostaining rates for OX40 in IDCa, DCIS and fibroadenomas from breast tissues were 85.0%, 66.7% and 38.7% respectively, showing a significant difference in OX40 expression among IDCa, DCIS and fibroadenoma of breast (z=5.206, P=0.001). Increased staining intensity of OX40 was associated with TNM stages (z=2.112, P=0.017). Meanwhile, a relation of OX40 expression with lymph node metastatic status in IDCa was found (P=0.041). The expression of OX40L did not show any obvious difference among IDCa, DCIS and fibroadenomas from breast tissues. OX40L expression was also not related to histopathological parameters in IDCa except for progesterone receptor (PR) being positive (P=0.005). However, a high coincidental positive rate for OX40 and OX40L was observed in biopsy samples with IDCa (P=0.017, Kappa=0.231). The present results suggest that high OX40 expression may be associated with malignant transformation, progression, invasion and metastasis in breast cancer biology.}, } @article {pmid20631061, year = {2010}, author = {Dietz, L and Esser, PR and Schmucker, SS and Goette, I and Richter, A and Schnölzer, M and Martin, SF and Thierse, HJ}, title = {Tracking human contact allergens: from mass spectrometric identification of peptide-bound reactive small chemicals to chemical-specific naive human T-cell priming.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {117}, number = {2}, pages = {336-347}, doi = {10.1093/toxsci/kfq209}, pmid = {20631061}, issn = {1096-0929}, mesh = {Allergens/chemistry/*metabolism ; Benzenesulfonates/chemistry/*metabolism/toxicity ; Cells, Cultured ; Dendritic Cells/drug effects/immunology/metabolism ; *Dermatitis, Contact ; Dinitrochlorobenzene/chemistry/*metabolism/toxicity ; Humans ; Lymphocyte Activation/drug effects/immunology ; Peptide Fragments/chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; T-Lymphocytes/drug effects/immunology/*metabolism ; }, abstract = {Modification of proteins by reactive small chemicals is a key step in the activation of chemical-specific T cells in allergic contact dermatitis (ACD). However, an integrated approach to characterize both the precise nature of chemically modified proteins and the chemical-specific T cells is currently lacking. Here, we analyze the molecular conditions for adduct formation of the strong human contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and its water-soluble form, 2,4-dinitrobenzenesulfonic acid (DNBS), with both an all amino acid-containing model peptide (± Cys) and the protein human serum albumin (HSA). Mass spectrometric detection and quantification revealed thiol-dependent peptide adduct formation at all pH values found in human skin layers. Highest modification rates were obtained with DNBS. Accordingly, DNBS- but not DNCB-modified human immature dendritic cells (iDC) induced in vitro primary human T-cell responses as did 2,4,6-trinitrobenzenesulfonic acid-modified iDC as measured by dinitrophenyl (DNP)- and trinitrophenyl (TNP)-specific T-cell proliferation and interferon gamma (IFN-γ) production in CD4(+) and CD8(+) T-cell subsets. Moreover, DNP-modified HSA protein effectively induced primary T-cell responses when processed by iDC. Thus, an integrated approach that combines efficient skin-related in chemico coupling analyses with an in vitro T-cell priming assay can be used to predict in vivo reactions of chemical contact allergens with extracellular and cellular proteins. This strategy supports the development of chemical-specific in vitro assays that are urgently required in predictive hazard identification and risk assessment of allergenic and nonallergenic chemicals.}, } @article {pmid20627320, year = {2010}, author = {Vieta, E and Morralla, C}, title = {Prevalence of mixed mania using 3 definitions.}, journal = {Journal of affective disorders}, volume = {125}, number = {1-3}, pages = {61-73}, doi = {10.1016/j.jad.2009.12.019}, pmid = {20627320}, issn = {1573-2517}, mesh = {Adult ; Bipolar Disorder/classification/diagnosis/*epidemiology/psychology ; Cross-Sectional Studies ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Humans ; International Classification of Diseases ; Male ; Middle Aged ; Personality Inventory/statistics & numerical data ; Psychometrics/statistics & numerical data ; Reproducibility of Results ; Socioeconomic Factors ; }, abstract = {OBJECTIVES: Mixed episodes are a combination of depressive and manic symptoms in bipolar disorder (BD). We want to identify the proportion of patients who have depressive symptoms during an acute episode and also the validity of current methods for its diagnosis.

MATERIAL AND METHOD: Cross-sectional multicentre study of patients with type I BD who are admitted to specialized units. 368 patients in 76 centres were included. The patients should have a well established diagnosis of BD and need hospitalisation. The severity of the disorder and clinical status were evaluated upon admission and discharge using CGI-BP-M clinical impression scales, the Hamilton depression scale (HAMD-17) and the Young mania rating scale (YMRS). Upon admission, the necessary criteria for diagnosing a mixed type episode were recorded according to DSM-IV-TR, ICD-10 and McElroy criteria. Clinical judgment of the current type of episode was also recorded.

RESULTS: Prevalence estimations for mixed episodes were: 12.9% according to DSM-IV-TR (n=45), 9% according to ICD-10 (n=31), 16.7% according to McElroy criteria (n=58), and 23.2% according to clinical judgment (n=81). Statistically significant differences were found between the estimated prevalence rates (Cochrane's Q-test, p<0.0001), with the maximum concordance level found between the McElroy and ICD-10 (Kappa=0.66, 95% CI, 0.54-0.77). The DSM-IV-TR criteria only present moderate concordance with ICD-10 (Kappa=0.65, 95% CI, 0.52 to 0.78) and McElroy criteria (Kappa=0.62, 95% CI, 0.50 to 0.74).

CONCLUSIONS: The definition of mixed episodes for BD must be revised to improve consensus and, consequently, therapeutic management. Current diagnostic systems, based on DSM-IV and IDC-10, only capture a limited proportion of patients suffering from mixed episodes, giving rise to important limitations concerning the therapeutic management of BP patients.}, } @article {pmid20623525, year = {2010}, author = {Martens, FM and van Kuppevelt, HJ and Beekman, JA and Heijnen, IC and D'Hauwers, KW and Heesakkers, JP}, title = {No primary role of ambulatory urodynamics for the management of spinal cord injury patients compared to conventional urodynamics.}, journal = {Neurourology and urodynamics}, volume = {29}, number = {8}, pages = {1380-1386}, doi = {10.1002/nau.20895}, pmid = {20623525}, issn = {1520-6777}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Netherlands ; Predictive Value of Tests ; Pressure ; Sensitivity and Specificity ; Spinal Cord Injuries/*complications/physiopathology ; Urinary Bladder/*innervation ; Urinary Bladder, Neurogenic/*diagnosis/etiology/physiopathology ; *Urodynamics ; Young Adult ; }, abstract = {AIMS: Adequate urodynamic assessment of bladder behavior is essential in spinal cord injury (SCI) patients. Ambulatory urodynamics are more sensitive to detect detrusor overactivity (DO) than conventional urodynamics. The primary objective of this study was to determine the value of ambulatory urodynamics for the diagnosis of DO in SCI patients compared to conventional urodynamics.

METHODS: Twenty-seven SCI patients who were suspected of DO underwent both conventional and ambulatory urodynamics at one day. A single involuntary detrusor contraction (IDC) was defined as a detrusor pressure rise of at least 10 cmH(2)O. DO according to the ICS definition was used in addition to minimize the influence of catheter artifacts. Outcome of urodynamics was used for decisions on treatment.

RESULTS: Ambulatory urodynamics were more sensitive to diagnose IDC and DO. Conventional urodynamics had a sensitivity of 82% and specificity of 75% for DO diagnosis compared to ambulatory urodynamics. Mean maximum detrusor pressures did not differ significantly between both urodynamics. When the maximum detrusor pressure at conventional urodynamics did not exceed 40 cmH(2)O, 83% (10/12) of patients had a mean maximum detrusor pressure under 40 cmH(2)O at ambulatory urodynamics. Although the inter-individual DO diagnostic agreement was lower for ambulatory than conventional urodynamics (58%, K = 0.201 vs. 77%, K = 0552), the treatment agreement was higher for ambulatory urodynamics (58% vs. 42%).

CONCLUSIONS: Ambulatory urodynamics do not seem necessary for diagnosis and risk assessment in SCI patients suspected for DO when conventional urodynamics are done properly. The exact role of urodynamics in treatment decision remains to be determined.}, } @article {pmid20613924, year = {2010}, author = {Ertas, U and Yalcin, E and Erdogan, F}, title = {Invasive ductal carcinoma with multiple metastases to facial and cranial bones: a case report.}, journal = {European journal of dentistry}, volume = {4}, number = {3}, pages = {334-337}, pmid = {20613924}, issn = {1305-7464}, abstract = {Female breast cancer is one of the major causes of death among women. Metastatic tumors to the maxillo-facial bones are rare. We present diagnosis and treatment of multiple metastatic invasive ductal carcinoma involving massive and early stage the left half of the mandibular body, the floor of the orbit, maxilla, left parietal bone, the iliac bone and cervical and thoracal vertebras in a 36 years old female one and half years after operated.}, } @article {pmid20609586, year = {2010}, author = {Londero, V and Zuiani, C and Panozzo, M and Linda, A and Girometti, R and Bazzocchi, M}, title = {Surgical specimen ultrasound: is it able to predict the status of resection margins after breast-conserving surgery?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {6}, pages = {532-537}, doi = {10.1016/j.breast.2010.06.001}, pmid = {20609586}, issn = {1532-3080}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*surgery ; Carcinoma/*diagnostic imaging/*surgery ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm, Residual/*diagnostic imaging/pathology ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {PURPOSE: To evaluate the accuracy of surgical specimen ultrasound in the assessment of the status of resection margins after breast-conserving surgery.

METHODS AND MATERIALS: Sonographic examination of 46 surgical specimens of US-detectable malignant tumors was performed. Distance of the lesion from the specimen margins in four radial directions was measured and compared with distances measured on pathologic examination. Positive pathologic margins were defined when invasive or intraductal carcinoma was found within 2 mm of the specimen margin. Sensitivity, specificity, positive(PPV) and negative predictive values(NPV) of US in predicting surgical margins were calculated, considering both a 10-mm and a 4-mm sonographic threshold.

RESULTS: Of 184 margins(4 per lesion), pathology demonstrated 28 positive and 156 negative margins. Considering the 10-mm cut-off, US identified 32 positive and 152 negative margins, showing the following sensitivity, specificity, PPV and NPV: 28.5%, 84.6%, 25% and 86.8%, respectively. Considering the 4-mm cut-off, US identified 7 positive and 177 negative margins, with a sensitivity of 7.1%, a specificity of 96.8%, a PPV of 28.2% and a NPV of 85.3%. False-negative results were more frequent in case of invasive lobular carcinoma (20%) and presence of intraductal component (60%).

CONCLUSION: Sonography demonstrated a poor performance in the evaluation of the status of resection margins in breast specimens; however, because of the high NPV -both with 10-mm and 4-mm thresholds- it might be helpful in confirming complete excision of a US-detected neoplasm and in ruling out the presence of macroscopic invasive ductal carcinoma at surgical margins.}, } @article {pmid20607535, year = {2010}, author = {Nakajo, M and Kajiya, Y and Kaneko, T and Kaneko, Y and Takasaki, T and Tani, A and Ueno, M and Koriyama, C and Nakajo, M}, title = {FDG PET/CT and diffusion-weighted imaging for breast cancer: prognostic value of maximum standardized uptake values and apparent diffusion coefficient values of the primary lesion.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {37}, number = {11}, pages = {2011-2020}, pmid = {20607535}, issn = {1619-7089}, mesh = {Adult ; Aged ; Biological Transport ; Breast Neoplasms/*diagnosis/diagnostic imaging/*metabolism ; *Diffusion ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Middle Aged ; Multivariate Analysis ; Positron-Emission Tomography/*methods ; Prognosis ; Regression Analysis ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {PURPOSE: To correlate both primary lesion (18)F-fluorodeoxyglucose (FDG) maximum standardized uptake value (SUVmax) and diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) with clinicopathological prognostic factors and compare the prognostic value of these indexes in breast cancer.

METHODS: The study population consisted of 44 patients with 44 breast cancers visible on both preoperative FDG PET/CT and DWI images. The breast cancers included 9 ductal carcinoma in situ (DCIS) and 35 invasive ductal carcinomas (IDC). The relationships between both SUVmax and ADC and clinicopathological prognostic factors were evaluated by univariate and multivariate regression analysis and the degree of correlation was determined by Spearman's rank test. The patients were divided into a better prognosis group (n = 24) and a worse prognosis group (n = 20) based upon invasiveness (DCIS or IDC) and upon their prognostic group (good, moderate or poor) determined from the modified Nottingham prognostic index. Their prognostic values were examined by receiver operating characteristic analysis.

RESULTS: Both SUVmax and ADC were significantly associated (p<0.05) with histological grade (independently), nodal status and vascular invasion. Significant associations were also noted between SUVmax and tumour size (independently), oestrogen receptor status and human epidermal growth factor receptor-2 status, and between ADC and invasiveness. SUVmax and ADC were negatively correlated (ρ=-0.486, p = 0.001) and positively and negatively associated with increasing of histological grade, respectively. The threshold values for predicting a worse prognosis were ≥4.2 for SUVmax (with a sensitivity, specificity and accuracy of 80%, 75% and 77%, respectively) and ≤0.98 for ADC (with a sensitivity, specificity and accuracy of 90%, 67% and 77%, respectively).

CONCLUSION: SUVmax and ADC correlated with several of pathological prognostic factors and both indexes may have the same potential for predicting the prognosis of breast cancer.}, } @article {pmid20602789, year = {2010}, author = {Zagouri, F and Sergentanis, TN and Nonni, A and Papadimitriou, CA and Michalopoulos, NV and Domeyer, P and Theodoropoulos, G and Lazaris, A and Patsouris, E and Zogafos, E and Pazaiti, A and Zografos, GC}, title = {Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {353}, pmid = {20602789}, issn = {1471-2407}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; HSP90 Heat-Shock Proteins/*metabolism ; Humans ; Hyperplasia/metabolism/pathology ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Precancerous Conditions/*metabolism/pathology ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).

METHODS: Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC.

RESULTS: Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC.

CONCLUSION: The above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs.}, } @article {pmid20601817, year = {2010}, author = {Mori, Y and Ohtsuka, T and Tsutsumi, K and Yasui, T and Sadakari, Y and Ueda, J and Takahata, S and Nakamura, M and Tanaka, M}, title = {Multifocal pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas detected by intraoperative pancreatic juice cytology. A case report.}, journal = {JOP : Journal of the pancreas}, volume = {11}, number = {4}, pages = {389-392}, pmid = {20601817}, issn = {1590-8577}, mesh = {Adenocarcinoma, Mucinous/*diagnosis/pathology/surgery ; Carcinoma, Pancreatic Ductal/*diagnosis/pathology/surgery ; Carcinoma, Papillary/*diagnosis/pathology/surgery ; Cytodiagnosis/methods ; Humans ; Male ; Middle Aged ; Monitoring, Intraoperative/methods ; Neoplasms, Multiple Primary/*diagnosis/pathology/surgery ; Pancreatectomy ; Pancreatic Juice/*cytology ; Pancreatic Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {CONTEXT: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been detected with increasing frequency as a result of the progression of diagnostic modalities. Recently, invasive ductal carcinoma of the pancreas concomitant with IPMNs has been the focus of attention.

CASE REPORT: We report the case of a 57-year-old man with multifocal ductal carcinomas of the pancreas concomitant with IPMNs detected by intraoperative cytology. During a follow-up for branch duct IPMNs, a stenotic lesion of the main duct in the pancreatic body was found by ERCP, and brush cytology of the stenosis revealed an adenocarcinoma. A distal pancreatectomy was proposed; however, intraoperative pancreatic juice cytology from the pancreatic head also revealed adenocarcinoma, and a total pancreatectomy was finally carried out. Pathological examination of the resected specimen showed multifocal ductal carcinomas and IPMNs in the distal pancreas, and invasive ductal carcinoma in the pancreatic head which had not been detected by preoperative imaging studies.

CONCLUSIONS: Surgeons should be aware of the possibility of multifocal carcinomas in patients with concomitant IPMNs. Intraoperative pancreatic juice cytology should always be performed in order to confirm the absence of carcinoma in the pancreas to be left in place after planned resection.}, } @article {pmid20598349, year = {2011}, author = {Karray-Chouayekh, S and Baccouche, S and Khabir, A and Sellami-Boudawara, T and Daoud, J and Frikha, M and Jlidi, R and Gargouri, A and Mokdad-Gargouri, R}, title = {Prognostic significance of p16INK4a/p53 in Tunisian patients with breast carcinoma.}, journal = {Acta histochemica}, volume = {113}, number = {5}, pages = {508-513}, doi = {10.1016/j.acthis.2010.05.002}, pmid = {20598349}, issn = {1618-0372}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/metabolism/mortality ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/mortality ; Cyclin-Dependent Kinase Inhibitor p16/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-mdm2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/*metabolism ; Tunisia ; bcl-2-Associated X Protein/metabolism ; }, abstract = {Infiltrating ductal carcinoma (IDC) of the breast is a result of genetic alterations that affect the regulation of the cell cycle check-point and apoptosis. The aim of the present study was analysis using immunohistochemical localization of mouse double minute-2 (mdm2), p16INK4a, p53, bax and bcl-2 markers in Tunisian patients with breast IDC and to determine if there was correlation with the major clinico-pathological parameters and with survival of patients. We showed that the expression of p53, p16INK4a, mdm2, bcl-2, and bax was observed in 46.3%, 20.7%, 38%, 50% and 11.9% of cases, respectively. Statistical analysis revealed that positive expression of mdm2 was associated with larger tumors (P=0.013), whereas bax positivity was more prevalent in younger patients and in tumors of smaller size (P=0.008 and P=0.012 respectively). Furthermore, the expression of p16INK4a correlated with advanced grade (P<0.0001), triple negative tumors (ER-/PR-/HER2-, P=0.001) and mdm2 expression (P=0.017). The absence of nuclear p53 accumulation was predictive of good prognosis as well as when it was associated with negative expression of p16INK4a. Our findings suggest that among the biomarkers tested, p16INK4a might have a useful clinical and prognostic significance in infiltrating ductal carcinoma of the breast.}, } @article {pmid20593406, year = {2010}, author = {Lopez-Garcia, MA and Geyer, FC and Natrajan, R and Kreike, B and Mackay, A and Grigoriadis, A and Reis-Filho, JS and Weigelt, B}, title = {Transcriptomic analysis of tubular carcinomas of the breast reveals similarities and differences with molecular subtype-matched ductal and lobular carcinomas.}, journal = {The Journal of pathology}, volume = {222}, number = {1}, pages = {64-75}, doi = {10.1002/path.2743}, pmid = {20593406}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Cluster Analysis ; Female ; Gene Expression Profiling/methods ; Humans ; Oligonucleotide Array Sequence Analysis/methods ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Signal Transduction ; }, abstract = {Tubular carcinoma (TC) is an uncommon special type of breast cancer characterized by an indolent clinical course. Although described as part of a spectrum of related lesions named 'low-grade breast neoplasia family' due to immunophenotypical and genetic similarities, TCs, low-grade invasive ductal carcinomas of no special type (IDC-NSTs), and classic invasive lobular carcinomas (ILCs) significantly differ in terms of histological features and clinical outcome. The aim of this study was to investigate whether pure TCs constitute an entity distinct from low-grade IDC-NSTs and from classic ILCs. To define the transcriptomic differences between TCs and IDC-NSTs and ILCs whilst minimizing the impact of histological grade and molecular subtype on their profiles, we subjected a series of grade- and molecular subtype-matched TCs and IDC-NSTs and molecular subtype-matched TCs and classic ILCs to genome-wide gene expression profiling using oligonucleotide microarrays. Unsupervised and supervised analysis revealed that TCs are similar at the transcriptomic level to grade- and molecular subtype-matched IDC-NSTs. However, subtle yet significant differences were detected and validated by quantitative reverse transcriptase-PCR, which may in part explain the reported more favourable outcome of TCs. Transcriptomic differences between TCs and molecular subtype-matched classic ILCs were more overt, predominantly due to lower expression of proliferation and cell cycle genes in TCs and down-regulation of cell adhesion/extracellular matrix-related genes in classic ILCs. Our results support the existence of a 'low-grade breast neoplasia family'; however, the transcriptomes of these lesions display small, yet important differences, which, together with their distinct biological behaviour, warrant their separation as discrete entities.}, } @article {pmid20593130, year = {2010}, author = {Amaral, P and Miguel, R and Mehdad, A and Cruz, C and Monteiro Grillo, I and Camilo, M and Ravasco, P}, title = {Body fat and poor diet in breast cancer women.}, journal = {Nutricion hospitalaria}, volume = {25}, number = {3}, pages = {456-461}, pmid = {20593130}, issn = {1699-5198}, mesh = {*Adipose Tissue ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; *Breast Neoplasms/metabolism ; Cross-Sectional Studies ; *Diet ; Female ; Humans ; Middle Aged ; Nutritional Status ; Pilot Projects ; }, abstract = {BACKGROUND: Breast cancer is the most common cancer in women worldwide. Differences in breast cancer incidence suggest a significant role of environmental factors in the aetiology: obesity, central adiposity, excess body fat and some dietary factors have been suggested as risk factors. This pilot study aimed to analyse the pattern of nutritional status, body fat, and the usual dietary intake among women diagnosed with breast cancer, consecutively referred to the Radiotherapy Department of the University Hospital Santa Maria.

PATIENTS AND METHODS: Throughout 2006, 71 consecutive women with breast cancer were included.

EVALUATIONS: weight (kg) & height (m), determined with a SECA(R) floor scale+stadiometer to calculate body mass index (BMI), waist circumference, percentage body fat with bipolar hand-held bio-impedance analysis (BF-306), Food Frequency Questionnaire validated for the Portuguese population to assess the usual dietary intake. Frequency analysis and Mann-Whitney U test were used to evaluate prevalence and associations.

RESULTS: Mean age was 60+/-12 (36-90) years. Invasive ductal carcinoma was the most frequent histology (68%), p<0.05. Most patients were in stage I (30%) or stage IIA (25%) of disease vs IIB (10%), IIIB (4%), IV (4%) or others (21%), p<0.05. Regarding nutritional status, 82% were overweight/obese; 89% of patients had a %body fat mass above the maximum limit of 30% vs only 8 (11%) with %body fat within normal range (p<0.002); 62% pts had a waist circumference>88 cm (prevalence analysis: p<0.04), and 61% of pts had gained weight after diagnosis. Univariate analysis did not show any association between histology, BMI, %body fat and waist circumference; by multivariate analysis there was an association between higher BMI, %body fat & aggressive histologies (p<0.005). Food frequency analysis showed a low intake of vegetables and whole grain cereals rich in complex carbohydrates (sources of fibre and phytochemicals), of fatty fish & nuts, primary sources of n-3 PUFA's and a high intake of saturated fat; more aggressive histologies were correlated with low intake of green leafy vegetables (p=0.05) and n-3 fatty acids food sources (p=0.01).

CONCLUSIONS: Our findings show a vast prevalence & homogeneous pattern of overweight/obesity, excessive body and abdominal fat, as well as weight gain after diagnosis, combined with diets deficient in protective nutrients. Further investigation is warranted as cancer rates in Portugal continue to increase.}, } @article {pmid20587515, year = {2010}, author = {Lo, PK and Lee, JS and Liang, X and Han, L and Mori, T and Fackler, MJ and Sadik, H and Argani, P and Pandita, TK and Sukumar, S}, title = {Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer.}, journal = {Cancer research}, volume = {70}, number = {14}, pages = {6047-6058}, pmid = {20587515}, issn = {1538-7445}, support = {P50 CA088843/CA/NCI NIH HHS/United States ; P50 CA088843-080008/CA/NCI NIH HHS/United States ; P50 CA088843-090008/CA/NCI NIH HHS/United States ; 1 P50 CA088843-08/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cell Line, Tumor ; Cyclin-Dependent Kinase 2/metabolism ; DNA Replication ; E2F Transcription Factors/metabolism ; Epigenesis, Genetic ; Forkhead Transcription Factors/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene Silencing ; *Genes, Tumor Suppressor ; Humans ; Retinoblastoma Protein/metabolism ; }, abstract = {The expression of several members of the FOX gene family is known to be altered in a variety of cancers. We show that in breast cancer, FOXF1 gene is a target of epigenetic inactivation and that its gene product exhibits tumor-suppressive properties. Loss or downregulation of FOXF1 expression is associated with FOXF1 promoter hypermethylation in breast cancer cell lines and in invasive ductal carcinomas. Methylation of FOXF1 in invasive ductal carcinoma (37.6% of 117 cases) correlated with high tumor grade. Pharmacologic unmasking of epigenetic silencing in breast cancer cells restored FOXF1 expression. Re-expression of FOXF1 in breast cancer cells with epigenetically silenced FOXF1 genes led to G(1) arrest concurrent with or without apoptosis to suppress both in vitro cell growth and in vivo tumor formation. FOXF1-induced G(1) arrest resulted from a blockage at G(1)-S transition of the cell cycle through inhibition of the CDK2-RB-E2F cascade. Small interfering RNA-mediated depletion of FOXF1 in breast cancer cells led to increased DNA re-replication, suggesting that FOXF1 is required for maintaining the stringency of DNA replication and genomic stability. Furthermore, expression profiling of cell cycle regulatory genes showed that abrogation of FOXF1 function resulted in increased expression of E2F-induced genes involved in promoting the progression of S and G(2) phases. Therefore, our studies have identified FOXF1 as a potential tumor suppressor gene that is epigenetically silenced in breast cancer, which plays an essential role in regulating cell cycle progression to maintain genomic stability.}, } @article {pmid20584319, year = {2010}, author = {Yoon, NK and Maresh, EL and Elshimali, Y and Li, A and Horvath, S and Seligson, DB and Chia, D and Goodglick, L}, title = {Elevated MED28 expression predicts poor outcome in women with breast cancer.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {335}, pmid = {20584319}, issn = {1471-2407}, support = {U24 CA086366/CA/NCI NIH HHS/United States ; 2 P30 CA16042-29/CA/NCI NIH HHS/United States ; CA-86366/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/*metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/*metabolism/secondary ; Disease Progression ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Mediator Complex/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate ; Tissue Array Analysis ; }, abstract = {BACKGROUND: MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression.

METHODS: Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed.

RESULTS: MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.

CONCLUSIONS: We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.}, } @article {pmid20582203, year = {2010}, author = {Vijayakumar, EK and Samel, MA and Bhalekar, SB and Pakhale, SM}, title = {A new stability indicating HPLC method for related substances in zolmitriptan.}, journal = {Indian journal of pharmaceutical sciences}, volume = {72}, number = {1}, pages = {119-122}, pmid = {20582203}, issn = {1998-3743}, abstract = {A sensitive, precise, specific, linear and stability indicating isocratic HPLC method was developed for the analysis of related substances in zolmitriptan. The potential known related substances are (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (impurity I) and (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (impurity II). The method can be used for the detection and quantification of known and unknown impurities and degradants in the drug substance zolmitriptan during routine analysis and also for stability studies in view of its capability to separate degradation products.}, } @article {pmid20574730, year = {2011}, author = {Uematsu, T and Kasami, M and Watanabe, J and Takahashi, K and Yamasaki, S and Tanaka, K and Tadokoro, Y and Ogiya, A}, title = {Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer?.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {18}, number = {4}, pages = {309-313}, doi = {10.1007/s12282-010-0211-z}, pmid = {20574730}, issn = {1880-4233}, mesh = {Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology/surgery ; Carcinoma/*drug therapy/metabolism/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have favorable disease-free survival rates. A few studies have suggested that lymphovascular invasion degree may play an important role in predicting pCR. This study aims to confirm the role of lymphatic invasion degree in predicting pCR in breast cancer patients after NAC.

METHODS: We retrospectively analyzed 120 patients treated with NAC and surgery. The following pathological features were evaluated on surgical specimens after NAC: histological grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), lymphovascular invasion degree, intratumoral necrosis positivity, and axillary lymph node positivity.

RESULTS: pCR and marked response were achieved in 12% (14/120) and 35% (42/120), respectively, of 120 breast cancers in 120 women. Breast cancers with pCR or marked response were classified as chemosensitive. The remaining 64 breast cancers (53%) were classified as chemoresistant. Severe lymphovascular invasion (P = .003), large tumor size (P = .029), ER positivity (P = .001), and PR positivity (P = .006) were significantly associated with chemoresistant breast cancer. Invasive ductal carcinoma (P = .028) and HER-2 positivity (P < .0001) were significantly associated with chemosensitive breast cancer. On multivariate analysis, HER-2 positivity (P < .0001), invasive ductal carcinoma (P = .047), and marked/moderate lymphovascular invasion (P = .023) were the three factors that remained statistically significant in the model to predict histological therapeutic effect.

CONCLUSION: Lymphovascular invasion degree is one of the important factors to predict NAC efficacy for breast cancer.}, } @article {pmid20572082, year = {2010}, author = {Lotze, U and Egerer, R and Glück, B and Zell, R and Sigusch, H and Erhardt, C and Heim, A and Kandolf, R and Bock, T and Wutzler, P and Figulla, HR}, title = {Low level myocardial parvovirus B19 persistence is a frequent finding in patients with heart disease but unrelated to ongoing myocardial injury.}, journal = {Journal of medical virology}, volume = {82}, number = {8}, pages = {1449-1457}, doi = {10.1002/jmv.21821}, pmid = {20572082}, issn = {1096-9071}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*virology ; Enterovirus/isolation & purification ; Enterovirus Infections/pathology/virology ; Female ; Heart/virology ; Humans ; Male ; Middle Aged ; Parvoviridae Infections/pathology/*virology ; Parvovirus B19, Human/*isolation & purification/pathogenicity ; Viral Load ; }, abstract = {While myocardial parvovirus B19 (B19V), aside from enteroviruses (EV) and adenoviruses (ADV), has recently been found often in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC), the pathogenetic significance of B19V genomes in those patients has not yet been sufficiently elucidated. In the present study, left ventricular endomyocardial biopsies from 24 patients with left ventricular ejection fraction (LVEF) below 55% due to IDC, and tissue from the right atrial appendage of 10 control patients undergoing bypass surgery with normal LVEF (>55%) were investigated for B19V, ADV, and EV genomes by specific nested polymerase chain reaction (PCR), by real time PCR or by reverse-transcription PCR, respectively. The myocardial tissue samples from the 10 controls were analyzed each in three different virological laboratories for B19V. In the IDC group, the frequency of the myocardial virus genomes found in 54% (13/24) of the patients was as follows: B19V: 50% (12/24), EV: 8% (2/24), including one patient with B19V and EV, and ADV: 0% (0/24). For comparison, the prevalence of B19V genomes was between 30% and 60% in the control group as detected in three different laboratories, but all these control subjects were EV- and ADV-negative. The number of B19V gene copies, however, was very low and similar both in the IDC and control group. In the majority of patients myocardial B19V persistence was associated with a low virus load irrespective of the underlying heart disease so that it may be of no importance in the pathogenesis of IDC.}, } @article {pmid20572042, year = {2010}, author = {Wei, B and Ding, T and Xing, Y and Wei, W and Tian, Z and Tang, F and Abraham, S and Nayeemuddin, K and Hunt, K and Wu, Y}, title = {Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma.}, journal = {Cancer}, volume = {116}, number = {19}, pages = {4463-4473}, doi = {10.1002/cncr.25352}, pmid = {20572042}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Neuroendocrine/*pathology ; Case-Control Studies ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasms, Hormone-Dependent/pathology ; Prognosis ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast, a pathologic entity newly defined in the 2003 World Health Organization classification of tumors, is a rare type of tumor that is not well recognized or studied. The purpose of this first case-controlled study is to reveal the clinicopathologic features, therapeutic response, and outcomes of patients with NEC of the breast.

METHODS: Seventy-four patients with NEC of the breast who were treated at The University of Texas M. D. Anderson Cancer Center were analyzed; 68 of them had complete clinical follow-up. Two cohorts of invasive mammary carcinoma cases were selected to pair with NEC to reveal demographic, pathologic, and clinical features at presentation, along with therapeutic response to treatment and patient outcomes.

RESULTS: NEC was more likely to be estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative. Despite similar age and disease stages at presentation, NEC showed a more aggressive course than invasive ductal carcinoma, with a higher propensity for local and distant recurrence and poorer overall survival. High nuclear grade, large tumor size, and regional lymph node metastasis were significant negative prognostic factors for distant recurrence-free survival; high nuclear grade and regional lymph node metastasis were also significant negative prognostic factors for overall survival. Although endocrine therapy and radiation therapy showed a trend toward improved survival, the small number of cases in this study limited the statistical power to reveal therapeutic benefits in NEC of the breast.

CONCLUSIONS: NEC is a distinct type of aggressive mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely different clinical entity.}, } @article {pmid20570624, year = {2010}, author = {Gruel, N and Lucchesi, C and Raynal, V and Rodrigues, MJ and Pierron, G and Goudefroye, R and Cottu, P and Reyal, F and Sastre-Garau, X and Fourquet, A and Delattre, O and Vincent-Salomon, A}, title = {Lobular invasive carcinoma of the breast is a molecular entity distinct from luminal invasive ductal carcinoma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {46}, number = {13}, pages = {2399-2407}, doi = {10.1016/j.ejca.2010.05.013}, pmid = {20570624}, issn = {1879-0852}, mesh = {Breast Neoplasms/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Carcinoma, Lobular/*genetics/mortality ; Female ; Genome, Human ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {In order to get insight into the molecular alterations of invasive lobular carcinoma (ILC), comparative genomic hybridisation array and transcriptomic analyses of a series of 62 oestrogens-positive (ER) invasive tumours [21 ILC and 41 invasive ductal carcinomas (IDC)] were performed. ILC and IDC shared highly recurrent regions of gains (1q12-q44(+) in more than 60% of the cases, 16pter-p11.2(+) in 45% and 63% of ILC and IDC, respectively) and losses (16q11.2-q24.2(-) in 84% of ILC and 67.5% of IDC and 17pter-p12(-) in 50% of ILC and IDC). However, ILC genomic signature was characterised by significantly more frequent losses of 13q21.33-q31.3 region (46.5%) and 22q11.23-q12.1 region (50%) whereas IDC showed significantly more frequent losses of 11q23.1-q23.2 region (in 44% of IDC). Nine different regions of high level amplifications were found in 38% of ILC (8/21 cases). Localised on chromosome 11 (11q13.2 region), the most frequent region of amplification encompassing the CCND1 and FGF3 genes was observed in five different ILC. Unsupervised hierarchical clustering of transcriptomic data showed that ILC and IDC clustered apart. Genes involved in cell adhesion, cell communication and trafficking, extra cellular matrix-interaction pathways or cell mobility contributed to this clustering. Despite these differences, the overall clinical outcome of ILC was identical to that of IDC. This molecular study highlights that lobular and oestrogens-positive ductal invasive carcinomas share common genomic alterations but that ILC present some specific molecular alterations. These molecular specificities should help with the identification of new therapeutic targets for ILC patients.}, } @article {pmid20565965, year = {2010}, author = {Suryadevara, A and Paruchuri, LP and Banisaeed, N and Dunnington, G and Rao, KA}, title = {The clinical behavior of mixed ductal/lobular carcinoma of the breast: a clinicopathologic analysis.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {51}, pmid = {20565965}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/surgery ; Cadherins/metabolism ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Carcinoma, Lobular/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: To date, the clinical presentation and prognosis of mixed ductal/lobular mammary carcinomas has not been well studied, and little is known about the outcome of this entity. Thus, best management practices remain undetermined due to a dearth of knowledge on this topic.

METHODS: In this paper, we present a clinicopathologic analysis of patients at our institution with this entity and compare them to age-matched controls with purely invasive ductal carcinoma (IDC) and historical data from patients with purely lobular carcinoma and also stain-available tumor specimens for E-cadherin. We have obtained 100 cases of ductal and 50 cases of mixed ductal/lobular breast carcinoma.

RESULTS: Clinically, the behavior of mixed ductal/lobular tumors seemed to demonstrate some important differences from their ductal counterparts, particularly a lower rate of metastatic spread but with a much higher rate of second primary breast cancers.

CONCLUSIONS: Our data suggests that mixed ductal/lobular carcinomas are a distinct clinicopathologic entity incorporating some features of both lobular and ductal carcinomas and representing a pleomorphic variant of IDC.}, } @article {pmid20557310, year = {2010}, author = {Tamaki, K and Sasano, H and Ishida, T and Miyashita, M and Takeda, M and Amari, M and Tamaki, N and Ohuchi, N}, title = {Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients.}, journal = {Cancer science}, volume = {101}, number = {9}, pages = {2074-2079}, doi = {10.1111/j.1349-7006.2010.01630.x}, pmid = {20557310}, issn = {1349-7006}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast/chemistry/pathology/surgery ; Breast Neoplasms/*metabolism/pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/*analysis ; Sensitivity and Specificity ; }, abstract = {The roles of core needle biopsy (CNB) have become well established as an important preoperative diagnostic method for breast lesions. We examined the concordance of histological types, nuclear grades, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status between CNB and surgical specimens in 353 cases. In addition, we analyzed the correlation between the number of CNB specimens obtained and accuracy of histological factors in order to explore the optimal number of CNB specimens. Between CNB and surgical specimens, concordance rates of histological type, nuclear grade, estrogen receptor (ER), and progesterone receptor (PgR) status (cut-off 0-<1%, 1-10%, and 10%<), and HER2 were 84.4%, 81.3%, 92.9%, and 89.3%, respectively. In 52 of 353 patients who were histopathologically diagnosed as ductal carcinoma in situ (DCIS) by CNB, final diagnosis was changed in to invasive ductal carcinoma (IDC) in surgical specimens. Statistically significant differences were detected in the discrepancy of the following factors between CNB and subsequent surgical specimens: histological types, nuclear grade, and PgR, between patients who received four or more cores and those who had received three or less cores. In addition, a similar tendency was also detected in estrogen receptor (ER) and HER2 as in the above, and the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens. Therefore, the optimal numbers of CNB were considered four at least in assessing the histological type, invasion, nuclear grade, hormone receptor status, and HER2 status of individual patients in the preoperative setting.}, } @article {pmid20553316, year = {2011}, author = {Samanta, S and Dey, P and Nijhawan, R}, title = {The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {22}, number = {2}, pages = {111-114}, doi = {10.1111/j.1365-2303.2010.00773.x}, pmid = {20553316}, issn = {1365-2303}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Female ; Fibroadenoma/pathology ; Humans ; *Micronuclei, Chromosome-Defective ; Micronucleus Tests/methods ; Middle Aged ; Neoplasm Staging ; }, abstract = {AIMS AND OBJECTIVES: Micronucleus (MN) scoring was carried out in benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) breast lesions to evaluate the role of MN as a biomarker in breast carcinomas. We also compared MN scores among different cytological grades of breast carcinoma.

MATERIALS AND METHODS: A total of 31 archival cases of fibroadenoma (FA) and 40 cases of infiltrating ductal carcinoma (IDC) were selected. The best May-Grünwald-Giemsa (MGG) stained fine needle aspiration cytology (FNAC) smear of each case was selected. The MN scoring was carried out independently by two observers on 1000 epithelial cells in oil immersion magnification (100× objective). The MN scores in FA and IDC were compared. The IDC cases were graded and the MN scores in different cytological grades of IDC were compared.

RESULTS: The mean MN scores (± standard deviation) in FA and IDC were 0.6 (± 1.1) and 13.6 (± 12.8), respectively, which were significantly different (P < 0.0001). There were seven grade 1, 13 grade 2, and 20 grade 3 IDCs. The mean MN scores (± standard deviation) of grade 1, 2 and 3 IDC were 4.3 (± 2.3), 11.95 (± 9.2) and 21.1 (± 16.7), respectively. An analysis of variance (anova) test showed a significant difference in MN score between all the grades of IDC (P < 0.05). However, there was no significant difference between fibroadenoma and grade 1 IDC. The Pearson's correlation coefficient showed positive correlations between MN scoring in the different grades of IDC.

CONCLUSIONS: MN scoring on routinely stained smears of IDCs was significantly higher than in fibroadenoma and was relatively easy, reliable and reproducible. As MN scoring of grade 1 IDC was similar to fibroadenoma, a larger study should be conducted to compare grade 1 IDC with other benign breast lesions.}, } @article {pmid20551659, year = {2010}, author = {Suda, K}, title = {Histopathology of the minor duodenal papilla.}, journal = {Digestive surgery}, volume = {27}, number = {2}, pages = {137-139}, doi = {10.1159/000286920}, pmid = {20551659}, issn = {1421-9883}, mesh = {Ampulla of Vater/pathology ; Enteroendocrine Cells/pathology ; Humans ; Pancreas/pathology ; Pancreatic Ducts/abnormalities/*pathology ; Pancreatic Neoplasms/pathology ; }, abstract = {The minor duodenal papilla, which is the orifice of the accessory, or dorsal, pancreatic duct/Santorini duct, mostly accompanied by pancreatic tissue, is situated about 2 cm ventroproximal to the major duodenal papilla. The patency of the terminal accessory pancreatic duct (APD) is recognized in about half or more of cases, and is related to the degree of fibrosis. The APD is lined with simple columnar epithelium and encircled by a smooth muscle layer. It is still controversial whether or not these muscle tissues comprise a sphincter muscle. Pancreatic tissue was found in about 80% of cases in the minor papilla. Among these cases, pancreatic tissue was continuous and/or closely related to the proper pancreas in about 40% of cases, and might have the same exocrine and endocrine morphologies/functions, suggesting that it is a portion of the dorsal pancreas and not an ectopic one. Endocrine cell micronests are frequently found in the ductal wall/surrounding area of the terminal APD, and predominantly consist of somatostatin- and/or pancreatic-polypeptide-containing cells. In cases of pancreas divisum, inadequate pancreatic juice drainage from the minor papilla might occur, resulting in dorsal pancreatitis. In the minor papilla, all ductal tumors may occur, such as an intraductal papillary mucinous neoplasms and invasive ductal carcinoma, but carcinoid tumors are rare.}, } @article {pmid20546336, year = {2010}, author = {Kim, HS and Kim, GY and Kim, YW and Park, YK and Song, JY and Lim, SJ}, title = {Stromal CD10 expression and relationship to the E-cadherin/beta-catenin complex in breast carcinoma.}, journal = {Histopathology}, volume = {56}, number = {6}, pages = {708-719}, doi = {10.1111/j.1365-2559.2010.03534.x}, pmid = {20546336}, issn = {1365-2559}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Cadherins/*metabolism ; Carcinoma/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neprilysin/*metabolism ; beta Catenin/*metabolism ; }, abstract = {AIMS: Previous investigations have indicated that stromal CD10 expression, and altered levels of both E-cadherin and beta-catenin, are associated with the biological aggressiveness of human carcinoma. The aim was to evaluate stromal CD10 expression and the association of stromal CD10 with E-cadherin and beta-catenin in breast carcinoma.

METHODS AND RESULTS: The expression of CD10, E-cadherin and beta-catenin was immunohistochemically analysed in tissue microarrays containing 104 cases of invasive ductal carcinoma (IDC) and 10 cases of ductal carcinoma in situ (DCIS). Stromal CD10 was detected in 49.5% (50/101) of the IDC. No immunoreactivity was identified in the stromal cells of normal breast, DCIS or intraductal components of IDC. Accumulation of the cytoplasmic beta-catenin was found in 87.0% (87/100) of the IDC. Stromal CD10 expression in IDC was significantly correlated with tumour size (P = 0.027), stage (P < 0.001) and histological grade (P = 0.006), the presence of nodal (P = 0.048) and distant (P = 0.015) metastases, oestrogen receptor-negative status (P = 0.016), cytoplasmic beta-catenin accumulation (P = 0.031) and lower overall survival rate (P = 0.041).

CONCLUSIONS: Stromal CD10 expression in IDC may constitute an important prognostic marker. Stromal CD10 expression with associated aggressive features might be related to aberrant beta-catenin expression.}, } @article {pmid20546222, year = {2010}, author = {Tan, E and Kuper-Hommel, M and Rademaker, M}, title = {Annular erythema as a sign of recurrent breast cancer.}, journal = {The Australasian journal of dermatology}, volume = {51}, number = {2}, pages = {135-138}, doi = {10.1111/j.1440-0960.2009.00621.x}, pmid = {20546222}, issn = {1440-0960}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*complications/diagnosis ; Carcinoma, Ductal, Breast/*complications/diagnosis ; Dermatitis/diagnosis ; Diagnosis, Differential ; Erythema/diagnosis/*etiology ; Female ; Humans ; Lupus Erythematosus, Cutaneous/diagnosis ; Middle Aged ; Neoplasm Recurrence, Local/*complications/diagnosis ; Skin/pathology ; Tinea/diagnosis ; }, abstract = {Three women with known breast cancer presented with very similar annular erythemas of their chest walls. All women were in remission from their breast cancer for at least 6 months. Their breast cancers had initially responded well to multi-modality treatment with no clinical or radiologic evidence of recurrence, until the development of the annular erythema. In the first case, the annular erythema was treated unsuccessfully as a dermatitis and then as tinea corporis. In the second case, subacute cutaneous lupus was considered but lupus antibodies were negative. In the third case, the annular erythema was promptly recognized and biopsied. Histology in all three cases revealed identical findings of invasive ductal carcinoma involving the lymphatics of the skin. Immunohistochemical staining of the carcinoma was positive for human epidermal growth factor receptor 2 but negative for oestrogen and progesterone receptors. Annular erythema can pose a wide differential but rarely has it been described as a sign of locally recurrent cancer. These cases highlight the importance of recognizing this entity in the oncologic patient, where prompt skin biopsies can confirm the diagnosis and allow early initiation of therapy.}, } @article {pmid20545940, year = {2010}, author = {Teller, P and Jefford, VJ and Gabram, SG and Newell, M and Carlson, GW}, title = {The utility of breast MRI in the management of breast cancer.}, journal = {The breast journal}, volume = {16}, number = {4}, pages = {394-403}, doi = {10.1111/j.1524-4741.2010.00938.x}, pmid = {20545940}, issn = {1524-4741}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/pathology/*surgery ; Early Detection of Cancer ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {Breast magnetic resonance imaging (MRI) is increasingly used in the evaluation of breast cancer. The impact of this modality on patient management at a single institution is evaluated in this paper. A retrospective review was performed for 114 breast cancer patients who had breast MRI as part of their diagnostic evaluation. Clinical information, mammograms, breast ultrasounds and MRI scans were reviewed to determine whether the MRI findings led to a change in patient management. Outcomes as the result of breast MRI were stratified as favorable and unfavorable. Ninety-five patients who had complete clinical, radiologic, and pathologic data were identified. The indications for breast MRI included: high risk screening (n = 3), diagnostic evaluation of disease after neo-adjuvant chemotherapy (n = 24) or prior to re-excision (n = 8), extent of in situ ductal, infiltrating ductal or infiltrating lobular disease histology (DCIS n = 3, IDC n = 24, ILC n = 17), identification of unknown primary (n = 2), assessment of contralateral breast (n = 4), recurrence surveillance (n = 5), and other (n = 5). MRI was concordant with clinical findings and other modalities in 70.5% of cases. MRI altered planned clinical management in 28 of 95 patients (29.5%). Management changes were favorable in 21 patients (75%). Diagnostic evaluation of the breast by MRI alters patient management in 30% of cases depending upon the indications. Alteration in patient management is favorable in 75% of cases. Evaluation of the breast by MRI alters the clinical management of nearly one-third of patients. Changes are favorable for the majority of these cases. Patients undergoing evaluation for contralateral disease, invasive lobular carcinoma and assessment of chemotherapeutic response may derive a more meaningful benefit from MRI.}, } @article {pmid20543543, year = {2010}, author = {Chien, T and Chou, J and Chang, T and Lin, C}, title = {Successful treatment of biphasic metaplastic sarcomatoid carcinoma of the breast by evaluation of immunohistochemical markers.}, journal = {Hematology/oncology and stem cell therapy}, volume = {3}, number = {2}, pages = {89-93}, doi = {10.1016/s1658-3876(10)50041-4}, pmid = {20543543}, issn = {1658-3876}, mesh = {Adult ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/administration & dosage ; Biomarkers, Tumor/*biosynthesis ; Biopsy ; *Breast Neoplasms/drug therapy/metabolism/pathology ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Chemotherapy, Adjuvant/methods ; Female ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/*biosynthesis ; Receptors, Progesterone/*biosynthesis ; Remission Induction ; *Sarcoma/drug therapy/metabolism/pathology ; Trastuzumab ; }, abstract = {Biphasic metaplastic sarcomatoid carcinoma (MSC) of the breast is rare and aggressive. Patients with metaplastic breast carcinomas tend to have poor outcomes with a high risk of recurrence following pri- mary surgery. Most reports have shown that systemic therapy appears to be less effective. We report a case of a 42-year-old female who presented with a large (14 cm) cauliflower breast mass. Biopsy revealed a poorly differentiated sarcoma. Initially, neo-adjuvant concurrent chemoradiotherapy with a sarcoma regimen was prescribed, and the tumor regressed to a large ulcer. Subsequent biopsy showed invasive ductal carcinoma (estrogen receptor, progesterone receptor stained weakly, 5%, Her2:2+) and disappearance of the sarcomatous component. Second-line neoadjuvant therapy was designed according to the histologic features of infiltrating ductal carcinoma, which led to nearly a complete response. A modified radical mastectomy of the right breast and axillary dissection was performed followed by monoclonal antibody (trastuzumab) therapy for 6 months due to the surgical specimen showing Her2:3+. The treatment course went smoothly with a good response. The patient had no evidence of disease at 18 months.}, } @article {pmid20542612, year = {2010}, author = {Igreja, V and Dias-Lambranca, B and Hershey, DA and Racin, L and Richters, A and Reis, R}, title = {The epidemiology of spirit possession in the aftermath of mass political violence in Mozambique.}, journal = {Social science & medicine (1982)}, volume = {71}, number = {3}, pages = {592-599}, doi = {10.1016/j.socscimed.2010.04.024}, pmid = {20542612}, issn = {1873-5347}, mesh = {Adult ; Female ; Health Status ; Humans ; Male ; Mental Disorders/*epidemiology ; Mozambique/epidemiology ; Patient Acceptance of Health Care ; Qualitative Research ; Severity of Illness Index ; Superstitions/psychology ; Survivors/*psychology ; Violence/*psychology ; *Warfare ; }, abstract = {In this article we assess the prevalence rates of harmful spirit possession, different features of the spirits and of their hosts, the correlates of the spirit possession experience, health patterns and the sources of health care consulted by possessed individuals in a population sample of 941 adults (255 men, 686 women) in post-civil war Mozambique in 2003-2004. A combined quantitative-qualitative research design was used for data collection. A major study outcome is that the prevalence rates vary according to the severity of the possession as measured by the number of harmful spirits involved in the affliction. The prevalence rate of participants suffering from at least one spirit was 18.6 percent; among those individuals, 5.6 percent were suffering from possession by two or more spirits. A comparison between possessed and non-possessed individuals shows that certain types of spirit possession are a major cause of health impairment. We propose that knowledge of both local understandings of harmful spirit possession and the community prevalence of this kind of possession is a precondition for designing public health interventions that sensitively respond to the health needs of people afflicted by spirits.}, } @article {pmid20541790, year = {2010}, author = {Bidgoli, SA and Ahmadi, R and Zavarhei, MD}, title = {Role of hormonal and environmental factors on early incidence of breast cancer in Iran.}, journal = {The Science of the total environment}, volume = {408}, number = {19}, pages = {4056-4061}, doi = {10.1016/j.scitotenv.2010.05.018}, pmid = {20541790}, issn = {1879-1026}, mesh = {Adolescent ; Adult ; Breast Neoplasms/*epidemiology/etiology/metabolism ; Environmental Exposure/statistics & numerical data ; Environmental Monitoring ; Epidemiological Monitoring ; Female ; Fibroadenoma/epidemiology/etiology/metabolism ; Humans ; Incidence ; Iran/epidemiology ; Middle Aged ; Oncogene Protein p21(ras)/metabolism ; Receptors, Aryl Hydrocarbon/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/metabolism ; Young Adult ; }, abstract = {Although the probability of having breast cancer increases with the age in general, this malignancy affects Iranian women at least one decade younger than their counterparts in other countries. However the underlying risk factors for the discrepancy have not been identified. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This study was aimed to compare the interactions between AhR and other fundamental genes (p53, K-Ras, ER, PgR) in a clinical setting. To conduct the immunohistochemical studies using appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinoma, 29 postmenopausal invasive ductal carcinoma and 30 breast fibroadenoma were selected retrospectively from 2004 to 2007 in the pathology department of Imam Khomeini hospital complex of Tehran University of Medical Sciences . Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental-induced tumors. AhR overexpression contributed to ER-/PgR-immunophenotype in young/premenopausal patients but the same pattern was not observed in benign and postmenopausal malignant tumors. It seems that early incidence of breast cancer in Iran is the result of interactions between hormonal and environmental factors.}, } @article {pmid20535543, year = {2011}, author = {Zhao, Y and Deng, C and Wang, J and Xiao, J and Gatalica, Z and Recker, RR and Xiao, GG}, title = {Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {127}, number = {1}, pages = {69-80}, doi = {10.1007/s10549-010-0972-2}, pmid = {20535543}, issn = {1573-7217}, mesh = {Apoptosis/genetics ; Base Sequence ; Breast Neoplasms/*genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Estrogen Receptor alpha/*metabolism ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/*genetics/*metabolism ; *Signal Transduction ; }, abstract = {In order to understand how microRNAs (miRNAs) regulate breast cancer tumorigenesis, a miRNA expression microarray screening was performed using RNA from formalin-fixed paraffin-embedded (FFPE) breast tissues, which included benign (n = 13), ductal carcinoma in situ (DCIS) (n = 16), and invasive ductal carcinoma (IDC) (n = 15). Twenty-five differentially expressed miRNAs (P < 0.01) were identified, of which let-7 family miRNAs were down-regulated in human breast cancer tissues at stages of DCIS and IDC compared to benign stage. We further found that there was an inverse correlation between ER-α expression and several members of let-7 family in the FFPE tissues. Next, we performed bioinformatics analysis and found that let-7 miRNA sequences match sequence in the 3'-UTR of estrogen receptor alpha (ER-α), suggesting ER-α may be a target of let-7, which was further confirmed by a number of experimental assays, including luciferase assay, protein expression, and mRNA expression. Overexpression of let-7 miRNAs in ER-positive breast cancer MCF7 cell line negatively affected ER-α activity. As expected, dampening of the ER-α signaling by let-7 miRNAs inhibited cell proliferation, and subsequently triggered the cell apoptotic process in MCF7 cells. In conclusion, our findings indicate a new regulatory mechanism of let-7 miRNAs in ER-α mediated cellular malignant growth of breast cancer.}, } @article {pmid20534901, year = {2010}, author = {Liang, S and Singh, M and Gam, LH}, title = {The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian.}, journal = {Disease markers}, volume = {28}, number = {3}, pages = {149-165}, doi = {10.3233/DMA-2010-0694}, pmid = {20534901}, issn = {1875-8630}, mesh = {Aged ; Aged, 80 and over ; Breast/*metabolism ; China ; Chromatography, Liquid ; Cohort Studies ; Electrophoresis, Gel, Two-Dimensional ; *Ethnicity ; Female ; Humans ; India ; Malaysia ; Middle Aged ; Neoplasm Proteins/*metabolism ; Proteins/*metabolism ; Solubility ; Tandem Mass Spectrometry ; Water ; }, abstract = {Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.}, } @article {pmid20533549, year = {2011}, author = {Oka, K and Suzuki, T and Onodera, Y and Miki, Y and Takagi, K and Nagasaki, S and Akahira, J and Ishida, T and Watanabe, M and Hirakawa, H and Ohuchi, N and Sasano, H}, title = {Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation.}, journal = {International journal of cancer}, volume = {128}, number = {8}, pages = {1770-1782}, doi = {10.1002/ijc.25505}, pmid = {20533549}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology/therapy ; Cell Adhesion ; Cell Cycle ; Cell Movement ; *Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Phosphoric Monoester Hydrolases/antagonists & inhibitors/genetics/*metabolism ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult ; }, abstract = {Nudix-type motif 2 (NUDT2) hydrolyzes diadenosine 5',5'''-p1,p4-tetraphosphate (Ap4A) associated with various cellular functions. Previous studies demonstrated its regulation through estrogens, suggesting possible importance of NUDT2 in breast carcinoma. NUDT2, however, has not been examined in malignant tissues. Therefore, we examined its expression and functions in breast carcinoma. Immunohistochemistry for NUDT2 was examined by invasive ductal carcinoma (IDC: n = 145) and pure ductal carcinoma in situ (DCIS: n = 82), and NUDT2 mRNA was examined by real-time PCR in 9 DCIS, 19 IDC and 6 non-neoplastic breast tissues. We also used T47D breast carcinoma cells in in vitro studies. NUDT2 immunoreactivity was detected in 78% of DCIS and 63% of IDC, and NUDT2 mRNA level was significantly higher in DCIS or IDC than non-neoplastic breast. NUDT2 status was significantly correlated with Van Nuys classification, HER2 or Ki-67 in DCIS, and with stage, lymph node metastasis, histological grade or HER2 in IDC. NUDT2 status was significantly associated with adverse clinical outcome of IDC patients and proved an independent prognostic factor. Results of transfection experiments demonstrated that proliferation activity of T47D cells was significantly associated with NUDT2 expression level according to the treatment of estradiol and/or tamoxifen. NUDT2 expression was significantly decreased by estradiol, and it was also significantly decreased in T47D cells transfected with HER2 siRNA. These findings suggest that NUDT2 is an estrogen-repressed gene and is also induced by HER2 pathways in breast carcinoma cells. NUDT2 promotes proliferation of breast carcinoma cells and is a potent prognostic factor in human breast carcinomas.}, } @article {pmid20526721, year = {2010}, author = {Chen, CL and Chu, JS and Su, WC and Huang, SC and Lee, WY}, title = {Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {457}, number = {1}, pages = {53-61}, pmid = {20526721}, issn = {1432-2307}, mesh = {Antigens, Neoplasm/*biosynthesis/genetics ; Antimutagenic Agents/toxicity ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases/*biosynthesis/genetics ; Carcinoma in Situ/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Hypoxia/drug effects/genetics ; Cell Line, Tumor ; Cobalt/toxicity ; Female ; Gene Expression/drug effects ; Glucose Transporter Type 1/*biosynthesis/genetics ; Humans ; Hyperplasia ; Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis/genetics ; Immunohistochemistry ; Phenotype ; Precancerous Conditions/genetics/metabolism ; RNA, Messenger/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Hypoxia and acidosis are microenvironmental selection forces during somatic evolution in breast carcinogenesis. The effect of cobalt chloride (CoCl(2))-induced hypoxia on the expression of hypoxia-inducible factor (HIF)-1alpha, glucose transporter 1 (GLUT1), and carbonic anhydrase IX (CAIX) was assessed in breast cancer cells derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231) by reverse transcriptase-polymerase chain reaction and immunoblotting. We analyzed these proteins' expression in tissue samples from normal breast tissue, usual ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) using immunohistochemistry. CAIX mRNA was expressed constitutively in MDA-MB-231 cells but not in the other three cell lines. CAIX mRNA expression was increased after CoCl(2)-induced hypoxia in all four breast cancer cell lines. The expression of HIF-1alpha and GLUT1 proteins was increased after CoCl(2)-induced hypoxia in all breast cancer cell lines tested. Hypoxia significantly increased CAIX protein expression in primary cancer cells but not in metastatic ones. HIF-1alpha was not expressed in benign breast tissue, whereas it was significantly expressed in DH, ADH, DCIS, and IDC (p < 0.001). GLUT1 and CAIX were expressed only in DCIS (56.8% and 25.0%) and IDC (44.1% and 30.5%), with higher expression in high grade DCIS than low/intermediate grade DCIS (79.2% vs. 30.0%, p = 0.001 and 37.5% vs. 10.0%, p = 0.036, respectively). High CAIX expression was significantly associated with poor histological grade of IDC (p = 0.005). During breast carcinogenesis, the role of HIF-1alpha changes from response to proliferation to tumor progression. GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype.}, } @article {pmid20524058, year = {2010}, author = {Pal, SK and Lau, SK and Kruper, L and Nwoye, U and Garberoglio, C and Gupta, RK and Paz, B and Vora, L and Guzman, E and Artinyan, A and Somlo, G}, title = {Papillary carcinoma of the breast: an overview.}, journal = {Breast cancer research and treatment}, volume = {122}, number = {3}, pages = {637-645}, pmid = {20524058}, issn = {1573-7217}, support = {K12 CA001727/CA/NCI NIH HHS/United States ; K12 CA001727-16A1/CA/NCI NIH HHS/United States ; 2K12CA001727-16A1/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Papillary/*diagnosis/therapy ; Female ; Humans ; }, abstract = {Papillary carcinoma of the breast represents approximately 0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater in older postmenopausal women and, in relative terms, in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63, and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.}, } @article {pmid20522561, year = {2010}, author = {Mitra, A and Menezes, ME and Shevde, LA and Samant, RS}, title = {DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {32}, pages = {24686-24694}, pmid = {20522561}, issn = {1083-351X}, support = {R01 CA140472/CA/NCI NIH HHS/United States ; R01 CA140472-01A1/CA/NCI NIH HHS/United States ; 1R01CA140472-01A1/CA/NCI NIH HHS/United States ; }, mesh = {Cell Movement ; *Gene Expression Regulation, Neoplastic ; HSP40 Heat-Shock Proteins/*metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Mesoderm/*metabolism ; Models, Biological ; Molecular Chaperones/*metabolism ; Neoplasm Metastasis ; Nerve Tissue Proteins/*metabolism ; Phenotype ; Proteasome Endopeptidase Complex/metabolism ; Wnt Proteins/metabolism ; Wound Healing ; beta Catenin/*metabolism ; }, abstract = {We showed that expression of MRJ (DNAJB6) protein is lost in invasive ductal carcinoma, and restoration of MRJ(L) restricts malignant behavior of breast cancer and melanoma cells. However, the signaling pathways influenced by MRJ(L) are largely unknown. Our observations revealed that MRJ(L) expression causes changes in cell morphology concomitant with down-regulation of several mesenchymal markers, viz. vimentin, N-cadherin, Twist, and Slug, and up-regulation of epithelial marker keratin 18. Importantly, MRJ(L) expression led to reduced levels of beta-catenin, an epithelial mesenchymal transition marker, and a critical player in the Wnt pathway. We found that MRJ(L) up-regulates expression of DKK1, a well known Wnt/beta-catenin signaling inhibitor, that causes degradation of beta-catenin. Re-expression of DNAJB6 alters the Wnt/beta-catenin signaling in cancer cells, leading to partial reversal of the mesenchymal phenotype. Thus, MRJ(L) may play a role in maintaining an epithelial phenotype, and inhibition of the Wnt/beta-catenin pathway may be one of the potential mechanisms contributing to the restriction of malignant behavior by MRJ(L).}, } @article {pmid20519190, year = {2011}, author = {McLaughlin, CS and Petrey, C and Grant, S and Ransdell, JS and Reynolds, C}, title = {Displaced epithelium after liposuction for gynecomastia.}, journal = {International journal of surgical pathology}, volume = {19}, number = {4}, pages = {510-513}, doi = {10.1177/1066896910362990}, pmid = {20519190}, issn = {1940-2465}, mesh = {Adipose Tissue/metabolism/*pathology ; Adult ; *Artifacts ; Biomarkers/metabolism ; Breast Neoplasms, Male/diagnosis/metabolism ; Carcinoma, Ductal, Breast/diagnosis/metabolism ; Diagnosis, Differential ; Epithelial Cells/metabolism/*pathology ; Gynecomastia/metabolism/*pathology/surgery ; Humans ; Lipectomy/*adverse effects ; Male ; Postoperative Complications ; Surgery, Plastic/*adverse effects ; }, abstract = {The authors describe the case of a 36-year-old man with gynecomastia who was previously treated with liposuction of the breast for cosmetic purposes. Histologic examination of a subsequent excisional biopsy revealed nests of displaced epithelial cells in adipose tissue. Epithelial cell displacement is a well-known risk of core needle biopsies and fine-needle aspirations of breast lesions. However, to the authors' knowledge, epithelial displacement in gynecomastia after liposuction, mimicking invasive ductal carcinoma, has not previously been reported.}, } @article {pmid20519164, year = {2010}, author = {Azizi-Semrad, U and Krenbek, D and Hofbauer, G and Karanikas, G and Maldonado-Gonzalez, E and Pietschmann, P and Willheim, M}, title = {Cytokine profiling of human peripheral blood CD4+ T lymphocytes reveals a new Th-subpopulation (Th6) characterized by IL-6.}, journal = {European cytokine network}, volume = {21}, number = {2}, pages = {105-115}, doi = {10.1684/ecn.2010.0190}, pmid = {20519164}, issn = {1952-4005}, mesh = {CD4-Positive T-Lymphocytes/*metabolism ; Cytokines/*blood ; Flow Cytometry ; Humans ; Interleukin-6/*blood ; }, abstract = {The number of functional subsets of CD4+ T lymphocytes distinguished by their cytokine production has been extended in the last decade. The in vitro generation of a T cell subset characterized by IL-6 production has resurrected the question of cytokine co-expression patterns in T cells. In order to delineate these cells as a specific functional subpopulation in vivo, we profiled the cytokine production pattern of human peripheral blood CD4+ T lymphocytes across established subsets. We provide evidence for a new T cell subset Th6, with an IL-6 signature. Freshly isolated PBMC were analyzed using intracellular cytokine detection (IDC). Cytokine co-expression patterns of up to three cytokines, as well as their correlation with selected transcription factors, were determined in CD4+ T lymphocytes. Co-expression of two of these signature cytokines used for the definition of functional subsets, e.g. IL-4, IFN-gamma, IL-17 and IL-6 were observed, but nearly excluded the production of a third (or fourth) signature cytokine. In this respect, Th1 (key cytokine IFN-gamma), Th2 (IL-4), Th6 (IL-6) and Th17 (IL-17) subsets can be defined, along with overlaps of any two of them. In contrast, TNF-alpha and IL-2 are not signature cytokines, but their absence or expression in single cells introduces further divisions across established subsets. Our study supports the concept of a further functional T cell Th6 subset, and contributes to the reference cytokine profiles of healthy individuals relevant to further studies in a variety of disease states.}, } @article {pmid20514537, year = {2010}, author = {Teresa, DB and Santos, RA and Takahashi, CS and Carrara, HH and Moreira, HW and Mattos, LC and Lia-Neto, N and Cunha, LA and Bassi, CL and Soares, EG and Donadi, EA and Mello, ER and Soares, CP}, title = {Polymorphisms of Lewis and Secretor genes are related to breast cancer and metastasis in axillary lymph nodes.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {31}, number = {5}, pages = {401-409}, pmid = {20514537}, issn = {1423-0380}, mesh = {ABO Blood-Group System/genetics ; Adult ; Aged ; Aged, 80 and over ; Axilla/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; Fucosyltransferases/*genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphatic Metastasis/*genetics ; Middle Aged ; Phenotype ; *Polymorphism, Single Nucleotide ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {ABH and Lewis antigen expression has been associated with cancer development and prognosis, tumor differentiation, and metastasis. Considering that invasive ductal breast carcinoma (IDC) presents multiple molecular alterations, the aim of the present study was to determine whether the polymorphism of ABO, Lewis, and Secretor genes, as well as ABO phenotyping, could be associated with tumor differentiation and lymph nodes metastasis. Seventy-six women with IDC and 78 healthy female blood donors were submitted to ABO phenotyping/genotyping and Lewis and Secretor genotyping. Phenotyping was performed by hemagglutination and genotyping by the polymerase chain reaction with sequence-specific primers. ABO, Lewis, and Secretor genes were classified by individual single nucleotide polymorphism at sites 59, 1067, 202, and 314 of the Lewis gene, 428 of the Secretor gene, and 261 (O1 allele), 526 (O2 and B allele), and 703 (B allele). No association was found between breast cancer and ABO antigen expression (P = 0.9323) or genotype (P = 0.9356). Lewis-negative genotype was associated with IDC (P = 0.0126) but not with anatomoclinical parameters. Nonsecretor genotype was associated with axillary lymph node metastasis (P = 0.0149). In conclusion, Lewis and Secretor genotyping could be useful to predict respectively breast cancer susceptibility and axillary lymph nodes metastasis.}, } @article {pmid20514413, year = {2010}, author = {Tan, BJ and Quek, KS and Wong, MY and Chui, WK and Chiu, GN}, title = {Liposomal M-V-05: formulation development and activity testing of a novel dihydrofolate reductase inhibitor for breast cancer therapy.}, journal = {International journal of oncology}, volume = {37}, number = {1}, pages = {211-218}, doi = {10.3892/ijo_00000669}, pmid = {20514413}, issn = {1791-2423}, mesh = {Antineoplastic Agents/administration & dosage/pharmacokinetics ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma/*drug therapy/metabolism/pathology ; Cell Survival/drug effects ; Chemistry, Pharmaceutical ; Dose-Response Relationship, Drug ; Drug Compounding/methods ; Drug Evaluation, Preclinical ; Female ; Folic Acid Antagonists/*administration & dosage/pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Liposomes/*chemical synthesis/metabolism/*therapeutic use ; Models, Biological ; Spiro Compounds/administration & dosage/chemical synthesis/therapeutic use ; Tetrahydrofolate Dehydrogenase/metabolism ; Time Factors ; Triazines/administration & dosage/chemical synthesis/therapeutic use ; Tumor Cells, Cultured ; }, abstract = {In the management of metastatic breast cancer, fewer recognized therapeutic standards are available as compared to the early stages of the disease. Thus, it is pertinent to search for new, effective therapy to improve survival, tolerability and quality of life of patients. In this study, a liposomal formulation was developed for a novel dihydrofolate reductase (DHFR) inhibitor, M-V-05. Drug encapsulation into liposomes was achieved by the citrate-based, pH gradient loading technique, with a final drug-to-lipid weight ratio of 0.1:1. The liposome formulation exhibited a sustained release profile of the encapsulated drug that followed first order release kinetics. Liposomal M-V-05 was found to be more effective than the standard DHFR inhibitor, methotrexate, and its activity was comparable to liposomal doxorubicin, with IC50 values of 37 and 59 microM achieved in MDA-MB-231 and JIMT-1 cells, respectively. Similar cytotoxicity was observed in primary patient samples of invasive ductal carcinoma of the breast. The combination of liposomal M-V-05 and liposomal doxorubicin in fixed molar ratio of 3:1 was additive in cytotoxicity, allowing the concentrations of liposomal doxorubicin and liposomal M-V-05 to be reduced by 62 and 46%, respectively. Taken together, liposomal M-V-05 represents a promising agent and offers a potential new adjuvant therapy for breast cancer treatment.}, } @article {pmid20510078, year = {2010}, author = {Li, L and Bi, XF and Xu, X and Liu, XY and Shen, GH and Guo, L and Yuan, YL and Wang, F and Wang, MR and Yang, HY}, title = {[Expression pattern of E-cadherin and p120-catenin in infiltrating lobular carcinoma and ductal carcinoma of the breast and its significance].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {32}, number = {4}, pages = {273-277}, pmid = {20510078}, issn = {0253-3766}, mesh = {Bone Neoplasms/secondary ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology/secondary ; Carcinoma, Lobular/*metabolism/pathology/secondary ; Catenins/*metabolism ; Cytoplasm/metabolism ; Diagnosis, Differential ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Survival Rate ; Delta Catenin ; }, abstract = {OBJECTIVE: To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC), and observe the different expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs.

METHODS: The patients with ILC admitted to our hospital from Jan 1999 to Dec 2006 and patients with IDC from Jan 2000 to Dec 2000 were included in this study. All their pathological slides were reviewed, and their clinical data and treatment variables were analyzed retrospectively. Then the expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs were detected by immunohistochemistry on tissue microarray.

RESULTS: The 5-year overall survival was 81.7% for ILCs and 79.1% for IDCs (P = 0.055). The 5-year disease-free survival was 61.8% for ILCs and 83.7% for IDCs (P < 0.001). Cytoplasmic localization of p120-catenin and loss of E-cadherin expression were more common in ILCs than in IDCs. The complete losses of E-cadherin in ILCs and IDCs were 55.6% (20/36) and 20.4% (45/221, P < 0.001), respectively. The p120-catenin showed a diffuse cytoplasmic localization in 66.7% (24/36) of ILCs and 16.3% (36/221) of IDCs (P < 0.001). Interestingly, the cytoplasmic localization of p120-catenin was clearly associated with the absence of E-cadherin expression in ILCs (P = 0.002), cytoplasmic localization of p120-catenin and absence of E-cadherin expression were observed 55.6% (20/36) in ILCs compared with 4.1% (9/221) in IDCs (P < 0.001).

CONCLUSION: ILC has several specific biological and prognostic characteristics which are different in IDC. Different expression patterns of E-cadherin and p120-catenin proteins can be helpful to recognize ILC from IDC.}, } @article {pmid20509867, year = {2010}, author = {Tang, JP and Tan, CP and Li, J and Siddique, MM and Guo, K and Chan, SW and Park, JE and Tay, WN and Huang, ZY and Li, WC and Chen, J and Zeng, Q}, title = {VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.}, journal = {Molecular cancer}, volume = {9}, number = {}, pages = {128}, pmid = {20509867}, issn = {1476-4598}, mesh = {Animals ; *Antibodies, Monoclonal ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Centrosome/*enzymology ; Dual-Specificity Phosphatases/genetics/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Hybridomas ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Neoplasms/genetics/*metabolism ; Rabbits ; }, abstract = {BACKGROUND: VHZ is a VH1-like (member Z) dual specific protein phosphatase encoded by DUSP23 gene. Some of the dual specific protein phosphatases (DSPs) play an important role in cell cycle control and have shown to be associated with carcinogenesis. Here, the expression of VHZ associated with cell growth and human cancers was investigated.

RESULTS: We generated a mouse monoclonal antibody (mAb clone#209) and rabbit polyclonal antibodies (rAb) against VHZ. We performed cell proliferation assay to learn how VHZ is associated with cell cycle by retroviral transduction to express VHZ, VHZ(C95S), and control vector in MCF-7 cells. Overexpression of VHZ [but not VHZ(C95S)] in MCF-7 cells promoted cell proliferation compared to control cells. shRNA-mediated knockdown of VHZ in MCF-7 cells showed that reduction of VHZ resulted in increased G1 but decreased S phase cell populations. Using indirect immunofluorescence, we showed that both exogenous and endogenous VHZ protein was localized at the centrosome in addition to its cytoplasmic distribution. Furthermore, using immunohistochemistry, we revealed that VHZ protein was overexpressed either in enlarged centrosomes (VHZ-centrosomal-stain) of some invasive ductal carcinomas (IDC) Stage I (8/65 cases) or in entire cytoplasm (VHZ-cytosol-stain) of invasive epithelia of some IDC Stage II/III (11/47 cases) of breast cancers examined. More importantly, upregulation of VHZ protein is also associated with numerous types of human cancer, in particular breast cancer. VHZ mAb may be useful as a reagent in clinical diagnosis for assessing VHZ positive tumors.

CONCLUSIONS: We generated a VHZ-specific mAb to reveal that VHZ has a novel subcellular localization, namely the centrosome. VHZ is able to facilitate G1/S cell cycle transition in a PTP activity-dependent manner. The upregulation of its protein levels in primary human cancers supports the clinical relevance of the protein in cancers.}, } @article {pmid20502570, year = {2009}, author = {Vijayakumar, EK and Dhore, DM and Kumar, M}, title = {HPLC method for simultaneous determination of impurities and degradation products in zonisamide.}, journal = {Indian journal of pharmaceutical sciences}, volume = {71}, number = {5}, pages = {521-526}, pmid = {20502570}, issn = {1998-3743}, abstract = {A gradient reversed phase HPLC method was developed and validated for the analysis of related substances in zonisamide (1,2-benzisoxazole-3-methanesulfonamide), using a Waters Symmetry C8 (150*3.9 mm) column with a flow rate of 1.0 ml/min and detection at 280 nm. The mobile phase component A consisted of a mixture of 0.02 M aqueous potassium dihydrogen phosphate-acetonitrile-methanol (75:10:15 v/v/v), pH adjusted to 4.0 with orthophosphoric acid. The mobile phase component B consisted of a mixture of 0.02 M aqueous potassium dihydrogen phosphate-acetonitrile-methanol (15:40:45 v/v/v), pH 2.0 with orthophosphoric acid. The limit of detection and limit of quantitation were in the range of 0.001-0.007% and 0.0035-0.25% respectively with respect to sample concentration of 2 mg/ml. The method was linear in the range of LOQ level to 200% of specified limits for II-VIII (< 0.10%, r(2)= 0.9958-0.9999). The method is sensitive, specific, linear, accurate, precise and stability-indicating for the detection and quantitation of precursors (viz., 4-hydroxycoumarin, 1,2-benzisoxazole-3-acetic acid, 1,2-benzisoxazole-3-bromoacetic acid, 1,2-benzisoxazole-3-methylbromide, sodium 1,2-benzisoxazole-3-methanesulfonate), process impurities (viz., 2-hydroxyacetophenone oxime and 3,3,3-tribromomethyl-1,2-benzisoxazole) and drug degradation products formed under stress conditions.}, } @article {pmid20500316, year = {2010}, author = {Dickinson, A and McCall, E and Twomey, B and James, N}, title = {Paediatric nurses' understanding of the process and procedure of double-checking medications.}, journal = {Journal of clinical nursing}, volume = {19}, number = {5-6}, pages = {728-735}, doi = {10.1111/j.1365-2702.2009.03130.x}, pmid = {20500316}, issn = {1365-2702}, mesh = {Focus Groups ; Humans ; Medication Errors/*nursing/*prevention & control ; *Pediatric Nursing ; Safety Management/*methods ; }, abstract = {AIMS AND OBJECTIVES: To understand paediatric nurses' understanding and practice regarding double-checking medication and identify facilitators and barriers to the process of independent double-checking (IDC).

BACKGROUND: A system of double-checking medications has been proposed as a way of minimising medication error particularly in situations involving high-risk medications, complex processes such as calculating doses, or high-risk patient populations such as infants and children. While recommendations have been made in support of IDC in paediatric settings little is known about nursing practice and the facilitators and barriers to this process.

DESIGN: A descriptive qualitative design was used.

METHODS: Data were collected via three focus group interviews. Six to seven paediatric nurses participated in homogenous groups based on level of practice. Data were analysed using thematic analysis.

CONCLUSIONS: This study demonstrates that, while IDC is accepted and promoted as best practice in a paediatric setting, there is a lack of clarity as to what this means. This study supports other studies in relation to the influence of workload, distraction and environmental factors on the administration process but highlights the need for more research in relation to the impact of the power dynamic between junior and senior nurses. The issue of automaticity has been unexplored in relation to nursing practice but this study indicates that this may have an important influence on how care is delivered to patients.

While the focus of this study was in the paediatric setting, the findings have relevance to other settings and population groups. The adoption of IDC in health care settings must have in place: policy and guidelines that clearly define the process of checking, educational support, an environment that supports peer critique and review, well-designed medication areas and accessible resources to support drug administration.}, } @article {pmid20499627, year = {2009}, author = {Mayun, AA and Obiano, SK and Shehu, SK and Abdulazeez, JO}, title = {Breast malignancies in a tertiary health setting in north-eastern Nigeria: a histopathological review.}, journal = {African journal of medicine and medical sciences}, volume = {38}, number = {4}, pages = {337-341}, pmid = {20499627}, issn = {0309-3913}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Biopsy, Needle ; Breast Neoplasms/epidemiology/*pathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Middle Aged ; Neoplasm Staging ; Nigeria/epidemiology ; Registries ; Retrospective Studies ; Young Adult ; }, abstract = {Breast cancer is one of the most common malignancies that occurs in women. Most of the studies done on breast cancer in our setting are epidemiological. This study aims at determining the histopathological subtypes and various features of breast malignancies seen in our setting. The bench record books of the Department of Pathology, Federal Medical Centre Gombe were used to identify all the breast cancer cases seen from May 2000 to May 2007, after which the Haematoxylin and Eosin-stained slides and request forms were retrieved. The slides were reviewed based on the 2003 WHO classification of breast tumours. One hundred and thirty four breast cancer cases were reviewed histologically. Invasive ductal carcinoma (NOS) made up 66.6% (89/134), followed by invasive lobular carcinoma which comprised 9.7% (13/134). Medullary carcinoma was seen in 6.0% (8/134). Invasive papillary and sarcomatoid carcinomas comprised 3.0% (4/134) each. Invasive ductal carcinomas were graded as follows: grade I - 12%, grade II - 22.5%, and grade III - 65%. The majority of breast cancer cases occurred in the fourth and fifth decades of life. Invasive ductal carcinoma remains the most frequent histopathological subtype and most of the patients in this environment have grade III disease.}, } @article {pmid20495326, year = {2010}, author = {Moriya, T and Fukatsu, K and Ueda, S and Iwaya, K and Osaki, A and Yamamoto, J}, title = {[A case of giant advanced ulcerative breast cancer managed with epirubicin and cyclophosphamide followed by weekly paclitaxel].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {5}, pages = {907-910}, pmid = {20495326}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology ; Cyclophosphamide/administration & dosage/*therapeutic use ; Epirubicin/administration & dosage/*therapeutic use ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Paclitaxel/administration & dosage/*therapeutic use ; Positron-Emission Tomography ; Quality of Life ; Tomography, X-Ray Computed ; }, abstract = {We report a case of giant advanced breast cancer with skin ulceration and bleeding (T4cN3M0, Stage IIIC) in which a significant QOL improvement was achieved with epirubicin and cyclophosphamide (EC) followed by weekly paclitaxel. A 63- year-old postmenopausal woman presented in May 2008 with a giant ulcerated right breast tumor and extensive erythema of the involved skin. She had discovered the tumor the previous year, but had not sought medical advice or treatment. A core needle biopsy of the breast mass led to a diagnosis of an invasive ductal carcinoma negative for estrogen receptor, progester-one receptor, and HER2/neu protein expression. She received q3w 4 cycles of EC(E: 60 mg/m(2), C: 600 mg/m(2))and 12 cycles of weekly paclitaxel (80 mg/m(2)). Upon completion of this chemotherapy, the breast tumor and skin erythema had nearly disappeared. A mastectomy was then performed with partial resection of the muscle and axillary lymph node dissection. Pathological examination showed only focal residual tumor cells and complete disappearance of cancer cells in the lymph nodes (Grade 2). EC followed by weekly paclitaxel therapy was effective for the locally advanced ulcerative breast tumor, and significantly improved QOL in this patient with Stage III C advanced breast cancer.}, } @article {pmid20495324, year = {2010}, author = {Okamoto, T and Goto, M and Tomita, I and Murayama, A and Sawa, M and Noguchi, Y and Shimizu, A}, title = {[A case of recurrence of breast cancer 36 years after mastectomy treated with endocrine and chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {5}, pages = {899-902}, pmid = {20495324}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/pathology/surgery ; Fatal Outcome ; Female ; Humans ; Mastectomy ; Neoplasm Metastasis/diagnostic imaging/drug therapy ; Recurrence ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {In 2001, a 72-year-old woman, who had undergone left mastectomy for breast carcinoma 36 years ago, was admitted because of dysphagia. Chest CT showed pleural effusion in the right side and no tumor in the breast. Chest drainage was performed. Cytology of chest effusion revealed adenocarcinoma. A high serum CA15-3 level was noted. She was diagnosed with a pleural recurrence of breast cancer, so administration of CAF agents (4 courses) was started. Pleural effusion was improved and the serum CA15-3 level was reduced. She was then clinically followed on medication with oral anastrozole (AI). After 4 years, progression of disease was noted. The serum CA15-3 level was elevated. A tumor measuring 3 cm was confirmed on the right chest wall. The tumor was removed under local anesthesia and pathological findings showed invasive ductal carcinoma expressing estrogen receptor. Chemotherapy with taxane had to be withdrawn because of its side effect. Administration of S-1 was then started. The serum CA15-3 level was gradually elevated. Thereafter, the regimen was switched to combined S-1 and toremifene citrate. The serum CA15-3 level was reduced and sustained for several months. However, she died of multiple organ metastasis in 2008.}, } @article {pmid20493777, year = {2010}, author = {Zelini, P and Lilleri, D and Comolli, G and Rognoni, V and Chiesa, A and Fornara, C and Locatelli, F and Meloni, F and Gerna, G}, title = {Human cytomegalovirus-specific CD4(+) and CD8(+) T-cell response determination: comparison of short-term (24h) assays vs long-term (7-day) infected dendritic cell assay in the immunocompetent and the immunocompromised host.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {136}, number = {2}, pages = {269-281}, doi = {10.1016/j.clim.2010.04.008}, pmid = {20493777}, issn = {1521-7035}, mesh = {Adolescent ; Adult ; Aged ; CD4-Positive T-Lymphocytes/*physiology ; CD8-Positive T-Lymphocytes/*physiology ; Child ; Child, Preschool ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/immunology ; Dendritic Cells/immunology ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoassay/*methods ; Immunocompetence/*immunology ; *Immunocompromised Host ; Infant ; Male ; Middle Aged ; Organ Transplantation ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells were measured in the immunocompetent host as well as in 13 solid-organ transplant recipients (SOTR), and 12 young hematopoietic stem cell transplant recipients (HSCTR) by using a long-term (7-day) assay based on PBMC stimulation by HCMV-infected dendritic cells (iDC), and two short-term (24h) assays, one for CD4(+) stimulation by infected cell lysate (iCL), and the other for CD8(+) stimulation by a pool of 34 epitopic peptides (pep-pool). In the immunocompetent, the number of T-cells activated by either iCL or the pep-pool was significantly reduced with respect to iDC. In both SOTR and HSCTR, the number of T-cells activated by iDC was comparable to that activated by iCL or the pep-pool. A significant correlation between iDC-activated T-cells and T-cells activated by either iCL or the pep-pool was observed. In conclusion, whenever a rapid result is needed, short-term assays may efficiently replace the iDC assay.}, } @article {pmid20492722, year = {2010}, author = {Yamazoe, S and Tanaka, H and Sawada, T and Amano, R and Yamada, N and Ohira, M and Hirakawa, K}, title = {RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {29}, number = {1}, pages = {53}, pmid = {20492722}, issn = {1756-9966}, mesh = {Animals ; Blotting, Western ; *Cell Adhesion ; Cell Movement ; Cell Proliferation ; Humans ; Liver Neoplasms/genetics/*prevention & control/secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mucin 5AC/*antagonists & inhibitors/genetics/*metabolism ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/pathology/*prevention & control ; Phosphorylation ; RNA Interference ; RNA, Messenger/genetics ; RNA, Small Interfering/*pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.

METHODS: We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).

RESULTS: MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice.

CONCLUSIONS: Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.}, } @article {pmid20473628, year = {2010}, author = {Shigematsu, H and Nakamura, Y and Tanaka, K and Shiotani, S and Koga, C and Kawaguchi, H and Nishimura, S and Taguchi, K and Nishiyama, K and Ohno, S}, title = {A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment.}, journal = {International journal of clinical oncology}, volume = {15}, number = {6}, pages = {615-620}, pmid = {20473628}, issn = {1437-7772}, mesh = {Adult ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/pathology ; Carcinoma, Papillary/*drug therapy/metabolism/pathology ; Female ; Humans ; Inflammatory Breast Neoplasms/*drug therapy/metabolism/pathology ; Lymphatic Metastasis ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/*metabolism ; Trastuzumab ; Treatment Outcome ; }, abstract = {We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma.}, } @article {pmid20471822, year = {2010}, author = {Colleoni, M and Bagnardi, V and Rotmensz, N and Viale, G and Mastropasqua, M and Veronesi, P and Cardillo, A and Torrisi, R and Luini, A and Goldhirsch, A}, title = {A nomogram based on the expression of Ki-67, steroid hormone receptors status and number of chemotherapy courses to predict pathological complete remission after preoperative chemotherapy for breast cancer.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {46}, number = {12}, pages = {2216-2224}, doi = {10.1016/j.ejca.2010.04.008}, pmid = {20471822}, issn = {1879-0852}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/surgery ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/surgery ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Middle Aged ; *Nomograms ; Preoperative Care/methods ; Receptors, Steroid/*metabolism ; Remission Induction ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {BACKGROUND: Tools able to predict pathological complete response (pCR) to preoperative chemotherapy might improve treatment outcome.

PATIENTS AND METHODS: Data from 783 patients with invasive ductal carcinoma treated with preoperative chemotherapy and operated at the European Institute of Oncology were used to develop a nomogram using logistic regression model based on both categorical (clinical T and N, HER2/neu, grade and primary therapy) and continuous variables (age, oestrogen receptor (ER), progesterone receptor (PgR), Ki-67 expression and number of chemotherapy courses). The performance of the resulting nomogram was internally evaluated through bootstrapping methods. Finally the model was externally validated on a patient set treated in other institutions and subsequently operated at the EIO.

RESULTS: At multivariable analysis the probability of pCR was directly associated with Ki-67 expression (OR for 10% increase in the percentage of positive cells, 1.15, 95% confidence interval (CI), 1.03, 1.29) and number of chemotherapy courses (OR for one cycle increase, 1.31, 95% CI, 1.12, 1.53) and inversely associated with ER and PgR expression (ORs for 10% increase in the percentage of positive cells, 0.86, 95% CI 0.79, 0.93 and 0.82, 95% CI 0.69, 0.99, respectively). The nomogram for pCR based on these variables had good discrimination in training as well in validation set (AUC, 0.78 and 0.77).

CONCLUSION: The use of a nomogram based on the number of preoperative courses, degree of Ki-67 and steroid hormone receptors expression may be useful for predicting the probability of pCR and for the design of the proper therapeutic algorithm in locally advanced breast cancer.}, } @article {pmid20470359, year = {2010}, author = {Olguntürk, R and Kula, S and Sucak, GT and Ozdoğan, ME and Erer, D and Saygili, A}, title = {Peripheric stem cell transplantation in children with dilated cardiomyopathy: preliminary report of first two cases.}, journal = {Pediatric transplantation}, volume = {14}, number = {2}, pages = {257-260}, doi = {10.1111/j.1397-3142.2009.01215.x}, pmid = {20470359}, issn = {1399-3046}, mesh = {Cardiomyopathy, Dilated/diagnostic imaging/physiopathology/*surgery ; Child ; Echocardiography ; Female ; Heart Failure/diagnostic imaging/physiopathology/*surgery ; Humans ; Male ; *Peripheral Blood Stem Cell Transplantation ; Stroke Volume ; Time Factors ; Transplantation, Autologous ; }, abstract = {We report two pediatric patients with IDC who underwent autologous PSCT. Both cases were referred to our clinic for cardiac transplantation because of end-stage heart failure resistant to conventional therapy with digoxin, diuretics, ACE inhibitors, and sympathomimetics. They had ejection fractions below 35%. In each case, autologous stem cell transplantation was performed via the coronary arteries, and five wk after the procedure transthoracic echocardiography showed a striking gain in their ejection fractions and an improvement in the left ventricular dimensions compared with the initial measurements. Although heart transplantation is the only option for children with IDC, stem cell transplantation can lessen the waiting list mortality and prolong the time for a patient to wait for a suitable donor.}, } @article {pmid20466412, year = {2010}, author = {Kim, JH and Shin, MH and Kweon, SS and Park, MH and Yoon, JH and Lee, JS and Choi, C and Fackler, MJ and Sukumar, S}, title = {Evaluation of promoter hypermethylation detection in serum as a diagnostic tool for breast carcinoma in Korean women.}, journal = {Gynecologic oncology}, volume = {118}, number = {2}, pages = {176-181}, doi = {10.1016/j.ygyno.2010.04.016}, pmid = {20466412}, issn = {1095-6859}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/*genetics ; Carcinoma in Situ/blood/genetics ; Carcinoma, Ductal, Breast/*blood/*genetics ; Cytokines/genetics ; *DNA Methylation ; Female ; Humans ; Middle Aged ; Nuclear Proteins/genetics ; Promoter Regions, Genetic ; Receptors, Retinoic Acid/genetics ; Republic of Korea ; Tumor Suppressor Proteins/genetics ; Twist-Related Protein 1/genetics ; }, abstract = {OBJECTIVE: We have noted that quantitative multiplex-methylation specific PCR (QM-MSP) analysis of a key panel of genes may be useful as an ancillary tool for ductal carcinoma in situ (DCIS) detection in breast tissue. In this study, we investigated aberrant promoter hypermethylation of four genes as a means to detect epigenetic alterations specific to breast carcinoma in the serum of patients with DCIS and invasive ductal carcinoma (IDC).

METHODS: Two hundred forty-three serum samples from 89 patients with IDC, 30 patients with DCIS, and 125 age-matched healthy controls were examined. After DNA extraction and sodium bisulfite treatment, QM-MSP was performed for HIN-1, RASSF1A, RAR-beta, and Twist.

RESULTS: Overall significant differences in methylation levels were observed for HIN-1 (p=0.006), RAR-beta (p<0.001), RASSF1A (p=0.004), and Twist (p<0.001). All four genes showed significantly higher methylation frequencies in DCIS or IDC than in control subjects (p<0.001 for all comparisons). However, methylation frequencies were not significantly different between DCIS and IDC. In receiver-operating characteristic analysis, the two-gene combination (RAR-beta/RASSF1A) showed the best performance in distinguishing DCIS/IDC from control samples. The estimated specificity of this two-gene panel for detecting DCIS/IDC was 88.8%, and its sensitivity was 94.1%.

CONCLUSIONS: The quantitative detection of aberrant DNA methylation in serum samples may be a promising high throughput approach for the diagnosis of breast cancer including DCIS.}, } @article {pmid20466107, year = {2010}, author = {Jensen, AJ and Naik, AM and Pommier, RF and Vetto, JT and Troxell, ML}, title = {Factors influencing accuracy of axillary sentinel lymph node frozen section for breast cancer.}, journal = {American journal of surgery}, volume = {199}, number = {5}, pages = {629-635}, doi = {10.1016/j.amjsurg.2010.01.017}, pmid = {20466107}, issn = {1879-1883}, mesh = {Aged ; Axilla ; Breast Neoplasms/mortality/*pathology/*surgery ; Cohort Studies ; Databases, Factual ; False Negative Reactions ; Female ; Follow-Up Studies ; Frozen Sections/*methods ; Humans ; Immunohistochemistry ; Intraoperative Care/methods ; Lymph Node Excision/*methods ; Lymph Nodes/*pathology ; Mastectomy/methods ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Probability ; Retrospective Studies ; Risk Assessment ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy/*methods ; Survival Rate ; }, abstract = {BACKGROUND: Intraoperative sentinel lymph node (SLN) frozen section (FS) guides immediate axillary lymph node dissection in breast cancer patients.

METHODS: The Oregon Health & Science University pathology database was searched for SLN FS From October 1999 to January 1, 2009. Slides of positive cases were reviewed and metastasis sizes measured.

RESULTS: Of 416 cases, 129 were positive (31%) on permanent sections and immunohistochemistry, with 79 concordant and 50 false-negative FS. Accuracy was 88%, sensitivity 61%, and specificity 100%. FS accuracy for lobular carcinoma (76%) was lower than for invasive ductal carcinoma (88%) (P = .048). FS accuracy significantly differed by size of nodal tumor. For 49 cases of tumor 2-mm metastases, accuracy was 90% (P < .0001).

CONCLUSIONS: False-negative FS were predominantly small nodal tumor deposits not sampled at FS. Although accuracy was lower, SLN FS is still beneficial in lobular carcinoma, but not ductal carcinoma in situ.}, } @article {pmid20461805, year = {2010}, author = {Moccia, M and Pellecchia, MT and Erro, R and Zingone, F and Marelli, S and Barone, DG and Ciacci, C and Strambi, LF and Barone, P}, title = {Restless legs syndrome is a common feature of adult celiac disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {25}, number = {7}, pages = {877-881}, doi = {10.1002/mds.22903}, pmid = {20461805}, issn = {1531-8257}, mesh = {Adult ; Celiac Disease/diet therapy/*epidemiology ; Comorbidity ; Diet, Gluten-Free ; Female ; Humans ; Male ; Prevalence ; Restless Legs Syndrome/*epidemiology ; }, abstract = {Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption-related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age- and sex-matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 +/- 6.5). In the CD population, no significant correlation was found between RLS and either gluten-free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end-stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD.}, } @article {pmid20459777, year = {2010}, author = {Kakarala, M and Rozek, L and Cote, M and Liyanage, S and Brenner, DE}, title = {Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the U.S.--a SEER analysis.}, journal = {BMC cancer}, volume = {10}, number = {}, pages = {191}, pmid = {20459777}, issn = {1471-2407}, mesh = {Adult ; Breast Neoplasms/epidemiology/*ethnology/metabolism/*pathology ; Female ; Humans ; India/ethnology ; Middle Aged ; Neoplasm Staging ; Pakistan/ethnology ; Proportional Hazards Models ; Receptors, Estrogen/*biosynthesis ; Receptors, Progesterone/*biosynthesis ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND: Recent reports suggest increase in estrogen receptor (ER), progesterone receptor (PR) negative breast cancer yet little is known about histology or receptor status of breast cancer in Indian/Pakistani women.in the U.S.

METHODS: We examined the United States National Cancer Institute's Surveillance Epidemiology and End Results (SEER) Cancer program to assess: a) frequency of breast cancer by age, b) histologic subtypes, c) receptor status of breast cancer and, d) survival in Indians/Pakistanis compared to Caucasians. There were 360,933 breast cancer cases diagnosed 1988-2006. Chi-Square analyses and Cox proportional hazards models, to estimate relative risks for breast cancer mortality after adjusting for confounders, were performed using Statistical Analysis Software 9.2.

RESULTS: Among Asian Indian/Pakistani breast cancer patients, 16.2% were < 40 yrs. old compared to 6.23% in Caucasians (p < 0.0001). Asian Indian women had more invasive ductal carcinoma (69.1 vs. 65.7%, p < 0.0001), inflammatory cancer (1.4% vs. 0.8, p < 0.0001) and less invasive lobular carcinoma (4.2% vs. 8.1%, p < 0.0001) than Caucasians. Asian Indian/Pakistani women had more ER/PR negative breast cancer (30.6% vs. 21.8%, p = 0.0095) than Caucasians. Adjusting for stage at diagnosis, age, tumor grade, nodal status, and histology, Asian Indian/Pakistani women's survival was similar to Caucasians, while African Americans' was worse.

CONCLUSIONS: Asian Indian/Pakistani women have higher frequency of breast cancer (particularly in age < 40), ER/PR negative invasive ductal and inflammatory cancer than Caucasians.}, } @article {pmid20459529, year = {2010}, author = {Zardawi, SJ and Zardawi, I and McNeil, CM and Millar, EK and McLeod, D and Morey, AL and Crea, P and Murphy, NC and Pinese, M and Lopez-Knowles, E and Oakes, SR and Ormandy, CJ and Qiu, MR and Hamilton, A and Spillane, A and Soon Lee, C and Sutherland, RL and Musgrove, EA and O'Toole, SA}, title = {High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype.}, journal = {Histopathology}, volume = {56}, number = {3}, pages = {286-296}, doi = {10.1111/j.1365-2559.2009.03475.x}, pmid = {20459529}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Middle Aged ; Phenotype ; Receptor, ErbB-2/*genetics ; Receptor, Notch1/*biosynthesis/genetics ; Signal Transduction/*physiology ; Tissue Array Analysis ; Young Adult ; }, abstract = {AIMS: Activation of Notch signalling results in hyperplasia and tumorigenesis in murine mammary epithelium. However, there is little information regarding the expression of Notch1 in premalignant lesions and early breast cancer. We investigated expression of Notch1 in breast cancer development and its association with molecular subtypes.

METHODS AND RESULTS: Immunohistochemical expression of Notch1 was determined in a murine model of mammary carcinogenesis and in breast tissue from two cohorts of breast cancer patients, the first (n=222) comprising a histological progression series and the second an outcome series of 228 patients with operable invasive ductal carcinoma. Enhanced expression of Notch1 protein was an early event in both murine and human breast cancer development with progressive increases in expression with the development of hyperplasia and malignancy. High Notch1 was not prognostic in the outcome cohort. There was, however, a highly significant association of high Notch1 protein with the HER-2 molecular subtype of breast cancer (P=0.008).

CONCLUSIONS: These data demonstrate that aberrant Notch regulation is an early event in mammary carcinogenesis and is associated with the HER-2 molecular subtype of breast cancer, and suggest the Notch signalling pathway may be a potential therapeutic target worthy of further investigation.}, } @article {pmid20452823, year = {2010}, author = {Barone, P and Poewe, W and Albrecht, S and Debieuvre, C and Massey, D and Rascol, O and Tolosa, E and Weintraub, D}, title = {Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Neurology}, volume = {9}, number = {6}, pages = {573-580}, doi = {10.1016/S1474-4422(10)70106-X}, pmid = {20452823}, issn = {1474-4465}, mesh = {Aged ; Antidepressive Agents/adverse effects/*therapeutic use ; Antiparkinson Agents/adverse effects/*therapeutic use ; Benzothiazoles/adverse effects/*therapeutic use ; Depressive Disorder/complications/*drug therapy ; Dopamine Agonists/adverse effects/therapeutic use ; Double-Blind Method ; Dyskinesias/complications/*drug therapy ; Europe ; Female ; Humans ; Male ; Parkinson Disease/complications/*drug therapy ; Pramipexole ; Psychiatric Status Rating Scales ; Severity of Illness Index ; South Africa ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease.

METHODS: We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score > or =5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score > or =2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22.

FINDINGS: Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were included in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0.7-3.7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug.

INTERPRETATION: Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease.}, } @article {pmid20447057, year = {2010}, author = {Lopes-Costa, PV and dos Santos, AR and dos Santos, LG and da Silva, BB}, title = {Evaluation of Ki-67 and Bcl-2 antigen expression in breast carcinomas of women treated with raloxifene.}, journal = {Cell proliferation}, volume = {43}, number = {2}, pages = {124-129}, pmid = {20447057}, issn = {1365-2184}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Cell Nucleus/metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Raloxifene Hydrochloride/*therapeutic use ; Receptors, Estrogen/analysis ; Selective Estrogen Receptor Modulators/*therapeutic use ; }, abstract = {OBJECTIVES: To evaluate the effect of raloxifene on Ki-67 and Bcl-2 antigen expression in operable, stage II, oestrogen-receptor-positive invasive ductal breast carcinomas.

MATERIALS AND METHODS: Twenty post-menopausal women who had taken 60 mg of raloxifene daily for 28 days prior to definitive surgery were enrolled in the investigation. Two tumour samples were obtained by incisional biopsy during the study, one at the time of confirmation of diagnosis of invasive ductal carcinoma and evaluation of oestrogen receptor status, and the other 29 days later, at the time of definitive surgery. Immunohistochemistry was performed on tumour samples, prior to and after raloxifene treatment, to evaluate Ki-67 and Bcl-2 expression. Friedman and McNemar tests were used for statistical analysis of the data, significance being established at 5%.

RESULTS: Mean percentage of Ki-67-stained nuclei was 24.86 +/- 2.95 prior to raloxifene treatment and 13.33 +/- 1.52 after treatment (P < 0.001). Prior to raloxifene treatment, only 9/20 cases (45%) were classified as Bcl-2-positive, whereas after treatment, 17/20 (85%) were classified as Bcl-2-positive (P < 0.013).

CONCLUSIONS: Raloxifene treatment significantly reduced Ki-67 antigen expression and increased Bcl-2 expression in breast carcinomas of post-menopausal women.}, } @article {pmid20441684, year = {2010}, author = {van den Berg, MG and Rasmussen-Conrad, EL and Wei, KH and Lintz-Luidens, H and Kaanders, JH and Merkx, MA}, title = {Comparison of the effect of individual dietary counselling and of standard nutritional care on weight loss in patients with head and neck cancer undergoing radiotherapy.}, journal = {The British journal of nutrition}, volume = {104}, number = {6}, pages = {872-877}, doi = {10.1017/S0007114510001315}, pmid = {20441684}, issn = {1475-2662}, mesh = {*Counseling ; Dietetics/*methods ; Female ; Head and Neck Neoplasms/complications/*radiotherapy ; Humans ; Male ; Malnutrition/*prevention & control ; Middle Aged ; Nurses ; *Patient-Centered Care ; Prospective Studies ; Radiotherapy/adverse effects ; *Weight Loss ; }, abstract = {Clinical research shows that nutritional intervention is necessary to prevent malnutrition in head and neck cancer patients undergoing radiotherapy. The objective of the present study was to assess the value of individually adjusted counselling by a dietitian compared to standard nutritional care (SC). A prospective study, conducted between 2005 and 2007, compared individual dietary counselling (IDC, optimal energy and protein requirement) to SC by an oncology nurse (standard nutritional counselling). Endpoints were weight loss, BMI and malnutrition (5% weight loss/month) before, during and after the treatment. Thirty-eight patients were included evenly distributed over two groups. A significant decrease in weight loss was found 2 months after the treatment (P = 0.03) for IDC compared with SC. Malnutrition in patients with IDC decreased over time, while malnutrition increased in patients with SC (P = 0.02). Therefore, early and intensive individualised dietary counselling by a dietitian produces clinically relevant effects in terms of decreasing weight loss and malnutrition compared with SC in patients with head and neck cancer undergoing radiotherapy.}, } @article {pmid20437638, year = {2010}, author = {Prvulović, I and Kardum-Skelin, I and Sustercić, D and Jakić-Razumović, J and Manojlović, S}, title = {Morphometry of tumor cells in different grades and types of breast cancer.}, journal = {Collegium antropologicum}, volume = {34}, number = {1}, pages = {99-103}, pmid = {20437638}, issn = {0350-6134}, mesh = {*Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; *Image Processing, Computer-Assisted ; Severity of Illness Index ; Software ; }, abstract = {The aim of the study was to compare morphometric characteristics of different types and grades of breast cancer. Morphometric analysis was performed using the SFORM software (Vamstec, Zagreb) on the May-Grünwald-Giemsa stained fine needle aspiration cytology (FNAC) breast tissue specimens. The study included 42 patients diagnosed with breast carcinoma by breast smear FNAC at Merkur University Hospital during the 2001-2005 period. Postoperative tumor histopathology and semi-quantitative tumor grading by the method of Elston and Ellis' showed invasive ductal carcinoma grade I in 10, invasive ductal carcinoma grade II in 9, invasive ductal carcinoma grade III in 13, and invasive lobular carcinoma in 13 patients, the latter also including a subtype of invasive tubulolobular carcinoma. The following parameters were assessed by use of Statistica 7.1 and chi2-test: tumor area, circumference, maximal radius, minimal radius, convexity, length, width, elongation, nucleus/cytoplasm ratio, and shape factor. Morphometric analysis yielded statistically significant differences among all study groups (p < 0.001). Morphometric parameters showed significant individual correlation with tumor type and grade, whereby the area, convexity and circumference were most significant at both nuclear and cellular level.}, } @article {pmid20435280, year = {2010}, author = {Ahmad, R and Lewis, S and Maharaj, D}, title = {A male patient from the West Indies with invasive ductal carcinoma in the right breast: a case report and literature review.}, journal = {Gender medicine}, volume = {7}, number = {2}, pages = {179-183}, doi = {10.1016/j.genm.2010.04.003}, pmid = {20435280}, issn = {1878-7398}, mesh = {Adult ; Age Distribution ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Axilla ; Biopsy ; *Breast Neoplasms, Male/diagnosis/epidemiology/therapy ; *Carcinoma, Ductal, Breast/diagnosis/epidemiology/therapy ; Chemotherapy, Adjuvant ; Delayed Diagnosis ; Humans ; Incidence ; Lymph Node Excision ; Male ; Mastectomy, Simple ; Neoplasm Staging ; Prognosis ; Sex Distribution ; Tomography, X-Ray Computed ; Trinidad and Tobago/epidemiology ; }, abstract = {BACKGROUND: Men with breast carcinoma have a poor prognosis, especially in the younger age group (30-40 years of age), because most breast enlargements in young men are dismissed as gynecomastia, resulting in an unnecessary delay in treatment.

OBJECTIVE: We describe the case of a young male patient with invasive ductal breast carcinoma.

CASE SUMMARY: In November 2005, a 30-year-old Afro-Caribbean man presented at St. Clair Medical Centre in Port of Spain, Trinidad, with a painless lump in the right breast. Diagnostic findings revealed that the patient had stage II invasive ductal carcinoma, for which he underwent a mastectomy with total axillary clearance.

CONCLUSION: Surgeons investigating unilateral breast swellings in young males should not dismiss them simply as gynecomastia, and should be wary of cancer.}, } @article {pmid20431215, year = {2010}, author = {Umanah, IN and Akhiwu, W and Ojo, OS}, title = {Breast tumours of adolescents in an African population.}, journal = {African journal of paediatric surgery : AJPS}, volume = {7}, number = {2}, pages = {78-80}, doi = {10.4103/0189-6725.62849}, pmid = {20431215}, issn = {0974-5998}, mesh = {Adolescent ; Age Distribution ; Age Factors ; Biopsy ; Breast Neoplasms/*pathology ; Breast Neoplasms, Male/*pathology ; Child ; Female ; Fibroadenoma/*pathology ; Hospitals, University ; Humans ; Incidence ; Male ; Nigeria ; Young Adult ; }, abstract = {BACKGROUND: Tumours of the breast are uncommon in childhood and adolescence. Patients in this age group often require a different approach to diagnosis and treatment. The purpose of this study is to highlight the clinicopathologic features of breast tumours in adolescents in a Nigerian city.

MATERIALS AND METHODS: Eighty-four breast tumour materials from patients aged 10-19 years were analyzed over a 10-year period at the Department of Pathology, University of Benin Teaching Hospital (UBTH), Benin City, Edo State, Benin City, Nigeria.

RESULTS: A majority of the breast tumours were benign. Fibroadenoma was the most common tumour with 46 cases (54.8%), followed by fibrocystic changes with 15 cases (17%). Malignancy was extremely rare in this group, with only one case (1.2%) of an invasive ductal carcinoma. Histologically, most tumours were indistinguishable from the adult types.

CONCLUSION: Fibroadenoma is the most common breast tumour in adolescents in Benin City, Nigeria. Breast cancer and male breast tumours are rare in this age group. Routine complete physical examination of children and adolescents should include breast examination.}, } @article {pmid20430465, year = {2010}, author = {Seifert, L and Toussaint, HM and Alberty, M and Schnitzler, C and Chollet, D}, title = {Arm coordination, power, and swim efficiency in national and regional front crawl swimmers.}, journal = {Human movement science}, volume = {29}, number = {3}, pages = {426-439}, doi = {10.1016/j.humov.2009.11.003}, pmid = {20430465}, issn = {1872-7646}, mesh = {Adaptation, Physiological/physiology ; Arm/*physiology ; Biomechanical Phenomena/physiology ; Body Mass Index ; Humans ; Male ; Models, Biological ; Movement/physiology ; *Power, Psychological ; Psychomotor Performance/*physiology ; *Swimming ; Videotape Recording ; Young Adult ; }, abstract = {The effects of skill level on index of arm coordination (IdC), mechanical power output (P(d)), and swim efficiency were studied in front crawlers swimming at different speeds. Seven national and seven regional swimmers performed an arms-only intermittent graded speed test on the MAD-system and in a free condition. The MAD-system measured the drag (D) and P(d). Swimming speed (v), stroke rate (SR), stroke length (SL), stroke index (SI), relative entry, pull, push, and recovery phase durations, and IdC were calculated. Swim efficiency was assessed from SI, the coefficient of variation of calculated hip intra-cyclic velocity variations (IVV), and the efficiency of propulsion generation, i.e., the ratio of v(2) to tangential hand speed squared (u(2)). Both groups increased propulsive continuity (IdC) and hand speed (u) and applied greater P(d) to overcome active drag with speed increases (p<.05). This motor organization adaptation was adequate because SI, IVV, and v(2)/u(2) were unchanged. National swimmers appeared more efficient, with greater propulsive continuity (IdC) and P(d) to reach higher v than regional swimmers (p<.05). The regional swimmers exhibited a higher u and lower SI, IVV, and v(2)/u(2) compared to national swimmers (p<.05), which revealed lower effectiveness to generate propulsion, suggesting that technique is a major determinant of swimming performance.}, } @article {pmid20429765, year = {2010}, author = {Kim, SJ and Moon, WK and Kim, SY and Chang, JM and Kim, SM and Cho, N}, title = {Comparison of two software versions of a commercially available computer-aided detection (CAD) system for detecting breast cancer.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {51}, number = {5}, pages = {482-490}, doi = {10.3109/02841851003709490}, pmid = {20429765}, issn = {1600-0455}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging ; False Positive Reactions ; Female ; Humans ; Mammography ; Middle Aged ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Retrospective Studies ; Sensitivity and Specificity ; *Software ; }, abstract = {BACKGROUND: The performance of the computer-aided detection (CAD) system can be determined by the sensitivity and false-positive marks rate, therefore these factors should be improved by upgrading the software version of the CAD system.

PURPOSE: To compare retrospectively the performances of two software versions of a commercially available CAD system when applied to full-field digital mammograms for the detection of breast cancers in a screening group.

MATERIAL AND METHODS: Versions 3.1 and 8.3 of a CAD software system (ImageChecker, R2 Technology) were applied to the full-field digital mammograms of 130 women (age range 36-80, mean age 53 years) with 130 breast cancers detected by screening.

RESULTS: The overall sensitivities of the version 3.1 and 8.3 CAD systems were 92.3% (120 of 130) and 96.2% (125 of 130) (P=0.025), respectively, and sensitivities for masses were 78.3% (36 of 46) and 89.1% (41 of 46) (P=0.024) and for microcalcifications 100% (84 of 84) and 100% (84 of 84), respectively. Version 8.3 correctly marked five lesions of invasive ductal carcinoma that were missed by version 3.1. Average numbers of false-positive marks per image were 0.38 (0.15 for calcifications, 0.23 for masses) for version 3.1 and 0.46 (0.13 for calcifications, 0.33 for masses) for version 8.3 (P=0.1420).

CONCLUSION: The newer version 8.3 of the CAD system showed better overall sensitivity for the detection of breast cancer than version 3.1 due to its improved sensitivity for masses when applied to full-field digital mammograms.}, } @article {pmid20424617, year = {2010}, author = {Wong, H and Lau, S and Yau, T and Cheung, P and Epstein, RJ}, title = {Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer.}, journal = {British journal of cancer}, volume = {102}, number = {9}, pages = {1391-1396}, pmid = {20424617}, issn = {1532-1827}, mesh = {Adult ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma in Situ/pathology ; Carcinoma, Ductal/mortality/*pathology/surgery ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/genetics ; Lymphatic Metastasis ; Middle Aged ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; Postmenopause ; Premenopause ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis/genetics ; Receptors, Progesterone/analysis/genetics ; Survival Rate ; Survivors ; }, abstract = {BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).

METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.

RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).

CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.}, } @article {pmid20424041, year = {2010}, author = {Saguy, T and Quinn, DM and Dovidio, JF and Pratto, F}, title = {Interacting like a body: objectification can lead women to narrow their presence in social interactions.}, journal = {Psychological science}, volume = {21}, number = {2}, pages = {178-182}, doi = {10.1177/0956797609357751}, pmid = {20424041}, issn = {1467-9280}, mesh = {Adolescent ; *Body Image ; Character ; Communication ; Female ; *Gender Identity ; Humans ; *Interpersonal Relations ; Male ; Self Concept ; *Social Identification ; *Stereotyping ; Verbal Behavior ; Women/*psychology ; Young Adult ; }, abstract = {The present experiment tested the impact of sexual objectification on women's behavior in social interactions. We predicted that when objectified, women would narrow their social presence by spending little time talking, particularly when interacting with men. Participants (males and females) gave an oral introduction of themselves to an alleged interaction partner (male or female). Objectification was manipulated by having participants believe their bodies were either visually inspected or not inspected during this introduction. Specifically, participants introduced themselves through a closed-circuit device in one of three conditions: body (videotaped from the neck down), face (videotaped from the neck up), or audio (no videotaping). Women who were in the body condition and thought they were interacting with men spent less time talking than participants in all other groups. In addition, the majority of women disliked the body condition, indicating that they found having their bodies gazed at aversive. Implications for women's behavior in mixed-sex contexts are discussed.}, } @article {pmid20423478, year = {2010}, author = {Lee, JH and Park, S and Park, HS and Park, BW}, title = {Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {34}, pmid = {20423478}, issn = {1477-7819}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancers and it has been reported to have some unique biologic and epidemiologic characteristics.

METHODS: Clinicopathological features of 95 patients with ILC, their relapse free survival (RFS) and overall survival (OS) were retrospectively investigated and compared with those of 3,621 patients with infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) between January 1984 and December 2005.

RESULTS: ILC constitutes 2.3% of all invasive breast cancers. There were no difference between the ILC and the IDC-NOS groups regarding age at diagnosis, tumor size, nodal status, and treatment modalities except hormone therapy. The ILC group showed more estrogen receptor expression, less HER-2 expression and higher bilaterality. RFS and OS of the ILC patients were similar to those of the IDC. IDC-NOS metastasized more frequently to the lung and bone, whereas, ILC to the bone and ovary.

CONCLUSIONS: The incidence of ILC was relatively low in Korean breast cancer patients. Comparing to IDC-NOS ILC showed some different features such as higher estrogen receptor expression, less HER-2 expression, higher bilaterality and preferred metastatic sites of bone and ovary. Contralateral cancers and bone and ovary evaluation should be considered when monitoring ILC patients.}, } @article {pmid20419158, year = {2010}, author = {Melki, MT and Saïdi, H and Dufour, A and Olivo-Marin, JC and Gougeon, ML}, title = {Escape of HIV-1-infected dendritic cells from TRAIL-mediated NK cell cytotoxicity during NK-DC cross-talk--a pivotal role of HMGB1.}, journal = {PLoS pathogens}, volume = {6}, number = {4}, pages = {e1000862}, pmid = {20419158}, issn = {1553-7374}, mesh = {Apoptosis/immunology ; CASP8 and FADD-Like Apoptosis Regulating Protein/biosynthesis/immunology ; Cell Communication ; Cell Separation ; Coculture Techniques ; Cytotoxicity, Immunologic/*immunology ; Dendritic Cells/*immunology/metabolism/virology ; Flow Cytometry ; HIV Infections/*immunology/metabolism/virology ; HIV-1/immunology ; HMGB1 Protein/*immunology/metabolism ; Humans ; Inhibitor of Apoptosis Proteins/biosynthesis/immunology ; Killer Cells, Natural/*immunology/metabolism/virology ; Microscopy, Confocal ; Oligonucleotide Array Sequence Analysis ; Receptor Cross-Talk ; Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology/metabolism ; Signal Transduction/immunology ; TNF-Related Apoptosis-Inducing Ligand/*immunology/metabolism ; }, abstract = {Early stages of Human Immunodeficiency Virus-1 (HIV-1) infection are associated with local recruitment and activation of important effectors of innate immunity, i.e. natural killer (NK) cells and dendritic cells (DCs). Immature DCs (iDCs) capture HIV-1 through specific receptors and can disseminate the infection to lymphoid tissues following their migration, which is associated to a maturation process. This process is dependent on NK cells, whose role is to keep in check the quality and the quantity of DCs undergoing maturation. If DC maturation is inappropriate, NK cells will kill them ("editing process") at sites of tissue inflammation, thus optimizing the adaptive immunity. In the context of a viral infection, NK-dependent killing of infected-DCs is a crucial event required for early elimination of infected target cells. Here, we report that NK-mediated editing of iDCs is impaired if DCs are infected with HIV-1. We first addressed the question of the mechanisms involved in iDC editing, and we show that cognate NK-iDC interaction triggers apoptosis via the TNF-related apoptosis-inducing ligand (TRAIL)-Death Receptor 4 (DR4) pathway and not via the perforin pathway. Nevertheless, once infected with HIV-1, DC(HIV) become resistant to NK-induced TRAIL-mediated apoptosis. This resistance occurs despite normal amounts of TRAIL released by NK cells and comparable DR4 expression on DC(HIV). The escape of DC(HIV) from NK killing is due to the upregulation of two anti-apoptotic molecules, the cellular-Flice like inhibitory protein (c-FLIP) and the cellular inhibitor of apoptosis 2 (c-IAP2), induced by NK-DC(HIV) cognate interaction. High-mobility group box 1 (HMGB1), an alarmin and a key mediator of NK-DC cross-talk, was found to play a pivotal role in NK-dependent upregulation of c-FLIP and c-IAP2 in DC(HIV). Finally, we demonstrate that restoration of DC(HIV) susceptibility to NK-induced TRAIL killing can be obtained either by silencing c-FLIP and c-IAP2 by specific siRNA, or by inhibiting HMGB1 with blocking antibodies or glycyrrhizin, arguing for a key role of HMGB1 in TRAIL resistance and DC(HIV) survival. These findings provide evidence for a new strategy developed by HIV to escape immune attack, they challenge the question of the involvement of HMGB1 in the establishment of viral reservoirs in DCs, and they identify potential therapeutic targets to eliminate infected DCs.}, } @article {pmid20410429, year = {2010}, author = {Tozaki, M and Hoshi, K}, title = {1H MR spectroscopy of invasive ductal carcinoma: correlations with FDG PET and histologic prognostic factors.}, journal = {AJR. American journal of roentgenology}, volume = {194}, number = {5}, pages = {1384-1390}, doi = {10.2214/AJR.09.3431}, pmid = {20410429}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*epidemiology/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/*epidemiology/metabolism ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Japan/epidemiology ; Magnetic Resonance Spectroscopy/*methods ; Middle Aged ; Positron-Emission Tomography/statistics & numerical data ; Prevalence ; Prognosis ; Protons ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {OBJECTIVE: The purpose of this article is to assess the histologic prognostic relevance of choline levels obtained using (1)H MR spectroscopy with a 1.5-T MR unit in patients with invasive breast cancer and to compare the observed choline levels with the standardized uptake value obtained using FDG PET.

MATERIALS AND METHODS: Single-voxel (1)H MR spectroscopy and PET/CT were performed for 50 patients with invasive ductal carcinoma (1.5-3 cm in size). The normalized choline signal was calculated using an external standard method.

RESULTS: Proton MR spectroscopy detected the presence of choline in 44 cases. The average normalized choline signal was 1.1 (range, 0-3.9). The average standardized uptake value was 6.5 (range, 1.1-23). The correlation (r) between the normalized choline signal and the standardized uptake value was 0.52 (p < 0.0001). The normalized choline signal was significantly correlated with nuclear grade (p = 0.0002), triple-negative breast cancer status (p = 0.0009), and estrogen receptor negativity (p = 0.007). The standardized uptake value was significantly correlated with nuclear grade (p = 0.0002), estrogen receptor negativity (p = 0.002), and triple-negative breast cancer status (p = 0.009). No significant differences were found between the progesterone receptor-positive and negative groups or between the human epidermal growth factor receptor 2-positive and negative groups.

CONCLUSION: The choline levels obtained using (1)H MR spectroscopy with a 1.5-T unit were well correlated with the standardized uptake value obtained using PET/CT and with the histologic prognostic parameters (nuclear grade, estrogen receptor status, and triple-negative lesion status).}, } @article {pmid20409316, year = {2010}, author = {Bae, JS and Choi, JS and Baik, SH and Park, WC and Song, BJ and Kim, JS and Lim, Y and Jung, SS}, title = {Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {32}, pmid = {20409316}, issn = {1477-7819}, mesh = {Adult ; Aged ; Breast Neoplasms/*blood/*genetics/pathology ; Carcinoma, Ductal, Breast/*blood/*genetics/pathology ; Comparative Genomic Hybridization ; DNA Copy Number Variations/*genetics ; DNA, Neoplasm/*blood ; Female ; *Genome, Human ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Prognosis ; }, abstract = {BACKGROUND: Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.

METHODS: DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.

RESULTS: Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).

CONCLUSION: Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.}, } @article {pmid20403244, year = {2010}, author = {Zhang, P and Xu, BH and Ma, F and Li, Q}, title = {[Clinicopathological characteristics and prognostic significance of young patients with triple-negative breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {32}, number = {2}, pages = {128-131}, pmid = {20403244}, issn = {0253-3766}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; *Breast Neoplasms/drug therapy/metabolism/pathology/surgery ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology/secondary/surgery ; Carcinoma, Medullary/drug therapy/metabolism/pathology/secondary/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Mastectomy/methods ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; Survival Rate ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the clinicopathological characteristics and prognosis in young patients with estrogen receptor (ER)-negative, progesterone receptor(PR)-negative, and Her-2-negative (triple-negative) breast cancer (TNBC).

METHODS: 94 young patients (< or = 35 years old) with TNBC at the Cancer Hospital of CAMS between January 1999 and December 2007 were included in this study. The clinicopathological features and prognosis of those 94 patients were retrospectively evaluated.

RESULTS: Among 786 young patients with breast cancer, 94 patients (12.0%) were triple-negative. The median age of the 94 young TNBC patients was 31 years.81 patients (86.2%) were diagnosed with invasive ductal carcinoma. 82.0% of the patients were classified as T1 or T2. The TNM stages included: 17 patients in stage I (18.1%), 48 in stage II (51.1%), 28 in stage III (29.8%) and 1 in stage IV (1.1%). 14 patients (14.9%) were diagnosed with lymphovascular invasion. The 1-, 3-, 5- and 7-year disease-free survival (DFS) was 88.3%, 66.9%, 59.7% and 59.7%, respectively. The corresponding overall survival (OS) rate was 98.9%, 85.6%, 72.9% and 69.6%, respectively. The univariate analysis showed that T stage, lymph node metastasis, clinical stage and lymphovascular invasion were correlated with the overall survival. However, only vascular invasion was showed to be an independent prognostic factor assessed by multivariate analysis. 33 patients developed recurrence or metastatic TNBC during the follow-up period. Among those 33 cases, 29 had recurrent or metastatic diseases within 3 years postoperatively and the other 4 cases after 3 years following surgery.

CONCLUSION: Young patients with TNBC represent distinctive clinicopathological and prognostic characteristics. Progression on tailored treatment for such population is still crucial. Further studies on rational individualized treatment regimen are warranted.}, } @article {pmid20400521, year = {2010}, author = {Broustas, CG and Ross, JS and Yang, Q and Sheehan, CE and Riggins, R and Noone, AM and Haddad, BR and Seillier-Moiseiwitsch, F and Kallakury, BV and Haffty, BG and Clarke, R and Kasid, UN}, title = {The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survival.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {16}, number = {11}, pages = {2939-2948}, doi = {10.1158/1078-0432.CCR-09-2351}, pmid = {20400521}, issn = {1557-3265}, support = {P01 CA074175/CA/NCI NIH HHS/United States ; CA68322/CA/NCI NIH HHS/United States ; CA74175/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Apoptosis ; Apoptosis Regulatory Proteins ; BRCA2 Protein/*metabolism ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Cell Line, Tumor ; Disease-Free Survival ; Down-Regulation ; Female ; Humans ; Middle Aged ; Prognosis ; RNA, Messenger/metabolism ; Transfection ; bcl-X Protein/metabolism ; }, abstract = {PURPOSE: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.

EXPERIMENTAL DESIGN: The interaction between BLID and Bcl-X(L) was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalin-fixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (>85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years).

RESULTS: BLID was found to interact with Bcl-X(L), and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P < 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P < 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P < 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002).

CONCLUSION: BLID is a new binding partner of Bcl-X(L) and a significant prognostic factor in breast cancer.}, } @article {pmid20397374, year = {2010}, author = {Laudenschlager, MD and Tyler, KL and Geis, MC and Koch, MR and Graham, DB}, title = {A rare case of synchronous invasive ductal carcinoma of the breast and follicular lymphoma.}, journal = {South Dakota medicine : the journal of the South Dakota State Medical Association}, volume = {63}, number = {4}, pages = {123-125}, pmid = {20397374}, issn = {0038-3317}, mesh = {Antigens, CD20/metabolism ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Lymphocytes/metabolism ; Lymphoma, Follicular/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {Synchronous presentation of breast cancer and lymphoma is extremely rare. Few cases are reported in the literature. We describe a case of invasive ductal carcinoma of the breast with micrometastasis to a non-sentinel lymph node and subsequent incidental finding of a low-grade follicular lymphoma in an axillary node of a 52-year-old woman. The characteristic immunohistochemical profile of the lymphoma is described.}, } @article {pmid20393391, year = {2010}, author = {Yang, HS and Chen, DY and Yuan, W and Yang, LL and Tsai, N and Lin, QS}, title = {Paresis associated with aconuresis caused by intervertebral disc calcification at c7-t1: a case report and review of the literature.}, journal = {Spine}, volume = {35}, number = {10}, pages = {E434-9}, doi = {10.1097/BRS.0b013e3181c71ebe}, pmid = {20393391}, issn = {1528-1159}, mesh = {Back Pain/etiology ; Calcinosis/*complications/*pathology/physiopathology ; Cervical Vertebrae/diagnostic imaging/pathology/surgery ; Decompression, Surgical ; Humans ; Intervertebral Disc/diagnostic imaging/pathology/surgery ; Intervertebral Disc Displacement/*complications/*pathology/physiopathology ; Magnetic Resonance Imaging ; Male ; Neurosurgical Procedures ; Paresis/etiology ; Spinal Canal/diagnostic imaging/pathology/surgery ; Spinal Cord/pathology/physiopathology ; Spinal Cord Compression/*etiology/*pathology/physiopathology ; Spinal Fusion/methods ; Thoracic Vertebrae/diagnostic imaging/pathology/surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology ; Young Adult ; }, abstract = {STUDY DESIGN: Case report.

OBJECTIVE: To report a case of a 19-year-old boy with intervertebral disc calcification (IDC) at C7-T1, who presented with paresis and aconuresis. Surgical outcome was assessed.

SUMMARY OF BACKGROUND DATA: IDC, commonly seen in the cervical spine region in children, is well-known as a self-limiting disorder with no or little symptoms. Surgical intervention is usually not required.

METHODS: A 19-year-old boy presented with acute back pain, progressive numbness, and weakness of both lower extremities and aconuresis for 1 week. There was no traumatic history or signs of infection. Radiograph, computed tomography with reconstruction, and magnetic resonance imaging revealed C7-T1 IDC with severe spinal cord compression. Decompression with anterior cervical corpectomy and fusion was performed.

RESULTS: Follow-up showed complete resolution of the back pain and complete recovery of motor power and sensory function in both lower extremities and return of normal micturition function. The patient had full recovery with no complications.

CONCLUSION: Serious neurologic deficit, especially a bladder dysfunction, caused by calcified intervertebral disc is rare. However, favorable outcome can be achieved in those cases where rapid diagnosis is made and followed by spinal cord decompression.}, } @article {pmid20390272, year = {2011}, author = {Dudeck, O and Bulla, K and Wieners, G and Ruehl, R and Ulrich, G and Amthauer, H and Ricke, J and Pech, M}, title = {Embolization of the gastroduodenal artery before selective internal radiotherapy: a prospectively randomized trial comparing standard pushable coils with fibered interlock detachable coils.}, journal = {Cardiovascular and interventional radiology}, volume = {34}, number = {1}, pages = {74-80}, doi = {10.1007/s00270-010-9845-7}, pmid = {20390272}, issn = {1432-086X}, mesh = {Aged ; Contrast Media/administration & dosage ; Duodenum/*blood supply ; Embolization, Therapeutic/*instrumentation ; Equipment Design ; Female ; Humans ; Iopamidol/administration & dosage/analogs & derivatives ; Liver Neoplasms/blood supply/diagnostic imaging/radiotherapy/*therapy ; Male ; Middle Aged ; Prospective Studies ; Radiography, Interventional/*methods ; Single-Blind Method ; Statistics, Nonparametric ; Stomach/*blood supply ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {The purpose of this study was compare embolization of the gastroduodenal artery (GDA) using standard pushable coils with the Interlock detachable coil (IDC), a novel fibered mechanically detachable long microcoil, in patients scheduled for selective internal radiotherapy (SIRT). Fifty patients (31 male and 19 female; median age 66.6 ± 8.1 years) were prospectively randomized for embolization using either standard coils or IDCs. Procedure time, radiation dose, number of embolization devices, complications, and durability of vessel occlusion at follow-up angiography were recorded. The procedures differed significantly in time (14:32 ± 5:56 min for standard coils vs. 2:13 ± 1:04 min for IDCs; p < 0.001); radiation dose for coil deployment (2479 ± 1237 cGycm[2] for standard coils vs. 275 ± 268 cGycm[2] for IDCs; p < 0.001); and vessel occlusion (17:18 ± 6:39 min for standard coils vs. 11:19 ± 7:54 min for IDCs; p = 0.002). A mean of 6.2 ± 1.8 coils (n = 27) were used in the standard coil group, and 1.3 ± 0.9 coils (p < 0.0001) were used in the IDC group (n = 23) because additional pushable coils were required to achieve GDA occlusion in 4 patients. In 2 patients, the IDC could not be deployed through a Soft-VU catheter. One standard coil dislodged in the hepatic artery and was retrieved. Vessel reperfusion was noted in only 1 patient in the standard coil group. Controlled embolization of the GDA with fibered IDCs was achieved more rapidly than with pushable coils. However, vessel occlusion may not be obtained using a single device only, and the use of sharply angled guiding catheters hampered coil pushability.}, } @article {pmid20388779, year = {2010}, author = {Lawson, JS and Glenn, WK and Salmons, B and Ye, Y and Heng, B and Moody, P and Johal, H and Rawlinson, WD and Delprado, W and Lutze-Mann, L and Whitaker, NJ}, title = {Mouse mammary tumor virus-like sequences in human breast cancer.}, journal = {Cancer research}, volume = {70}, number = {9}, pages = {3576-3585}, doi = {10.1158/0008-5472.CAN-09-4160}, pmid = {20388779}, issn = {1538-7445}, mesh = {Animals ; Antigens, Viral, Tumor/genetics ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/pathology/*virology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology/virology ; Genes, env ; Humans ; Immunohistochemistry ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Wnt1 Protein/biosynthesis/genetics ; }, abstract = {Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings.}, } @article {pmid20388392, year = {2010}, author = {Zhang, XL and Yang, GZ and Ding, HY}, title = {[Pathological study of radial sclerosing lesions].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {39}, number = {1}, pages = {10-13}, pmid = {20388392}, issn = {0529-5807}, mesh = {Adenocarcinoma/pathology ; Adolescent ; Adult ; Breast/*pathology ; Breast Diseases/metabolism/*pathology ; Breast Neoplasms/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Diagnosis, Differential ; Diagnostic Errors ; Female ; Humans ; Hyperplasia ; Keratin-14/metabolism ; Keratin-5/*metabolism ; Keratins/metabolism ; Middle Aged ; Sclerosis/metabolism/*pathology ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the pathological diagnostic features and the differential diagnosis of radial sclerosing lesions of the breast.

METHODS: Morphological observation and immunohistochemistry were applied to forty-four cases of radial sclerosing lesions of the breast.

RESULTS: All forty-four patients were females, the mean age was 40.3 years (range 17 to 54 years). In the 31 consultation cases, 13 were misdiagnosed as carcinoma. The lesions had a radiating outline, and a central scar area where squeezed or pressed irregular shaped tubules were frequently seen. Dilated tubules and proliferated ducts or lobules were seen radically arranged at the periphery accompanied sometimes with the apocrine glands or columnar cell metaplasia and hyperplasia. Aside, there were 14 cases displaying necroses and 8 cases showing atypical ductal hyperplasia. Immunostaining showed myoepithelial cells around the pseudo-infiltrating tubules, and the florid proliferating epithelial cells were positive for CK5/6.

CONCLUSIONS: Radial sclerosing lesions of the breast possess characteristic histological features, and may be misdiagnosed as carcinoma. The lesions should be differentiated from ductal carcinoma in situ, lobular neoplasia, tubular carcinoma and invasive ductal carcinoma.}, } @article {pmid20388391, year = {2010}, author = {Ma, YH and Wang, K and Li, L and Lu, ZH and Chen, J}, title = {[Expression of Twist, E-cadherin and N-cadherin in breast carcinoma and their clinical significance].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {39}, number = {1}, pages = {5-9}, pmid = {20388391}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Twist-Related Protein 1/*metabolism ; }, abstract = {OBJECTIVE: To investigate the expression of Twist, E-cadherin and N-cadherin in breast carcinoma tissue and to analyse their effects on the breast carcinoma differentiation, size, infiltration and metastasis of the breast carcinoma.

METHODS: The expression of Twist, E-cadherin and N-cadherin in 56 cases of breast invasive ductal carcinoma, 38 cases of invasive lobular carcinoma, 41 cases of carcinoma in situ and 10 cases of normal breast tissue was detected using immunohistochemistry.

RESULTS: (1) The expression rate of Twist in three types of breast carcinoma was 46.4% (26/56), 79.0% (30/38) and 26.8% (11/41) respectively, and the expression of Twist in invasive lobular carcinoma was significantly higher than that in invasive ductal carcinoma and carcinoma in situ (P = 0.002, P = 0.000). The expression rate of E-cadherin in three types of breast carcinoma was 78.6% (44/56), 29.0% (11/38) and 80.5% (33/41) respectively, and the expression of E-cadherin in invasive ductal carcinoma and carcinoma in situ was significantly higher than that in invasive lobular carcinoma (P = 0.000, P = 0.000). The expression rate of N-cadherin in three types of breast carcinoma was 53.6% (30/56), 68.4% (26/38) and 31.7% (13/41) respectively, and the expression of N-cadherin in invasive ductal carcinoma and invasive lobular carcinoma was significantly higher than that in carcinoma in situ (P = 0.033, P = 0.001). (2) In all the 135 cases, the expression of Twist was not correlated with that of E-cadherin (P = 0.005, Spearman correlation coefficient = -0.239), however, there was a positive correlation between the expression of Twist and N-cadherin and statistically significant(P = 0.000, Spearman correlation coefficient = 0.319). (3) In the invasive ductal carcinoma, the expression of N-cadherin in poorly-differentiated carcinoma was significantly higher than that of the moderately-or well-differentiated ones (P = 0.004). (4) In the invasive lobular carcinoma, the expression of Twist in cases with lymph node metastasis was significantly higher than that of cases without metastasis (P = 0.037).

CONCLUSIONS: Twist, E-cadherin and N-cadherin have different expression patterns in the three kinds of breast carcinoma. The positive expression of Twist was correlated to lymph node metastasis in invasive lobular carcinoma and the positive expression of N-cadherin was correlated to cell the tissue differentiation in invasive ductal carcinoma. Detection of the expression of these biomarkers may provide a valuable reference for the study of breast carcinoma progression, metastasis and for the judgment of the biological behavior of the carcinoma.}, } @article {pmid20375833, year = {2010}, author = {Mehta, VK and Algan, O and Griem, KL and Dickler, A and Haile, K and Wazer, DE and Stevens, RE and Chadha, M and Kurtzman, S and Modin, SD and Dowlatshahi, K and Elliott, KW and Rusch, TW}, title = {Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.}, journal = {American journal of clinical oncology}, volume = {33}, number = {4}, pages = {327-335}, doi = {10.1097/COC.0b013e3181d79d9e}, pmid = {20375833}, issn = {1537-453X}, mesh = {Aged ; Brachytherapy/adverse effects/instrumentation/*methods ; Breast/pathology/radiation effects ; Breast Neoplasms/pathology/*radiotherapy ; Electronics ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Radiotherapy Dosage ; Safety ; }, abstract = {OBJECTIVES: Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer.

METHODS: Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions.

RESULTS: Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events.

CONCLUSIONS: Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.}, } @article {pmid20371757, year = {2010}, author = {Tyson, AM and Gay, WE}, title = {Successful experience utilizing dexrazoxane treatment for an anthracycline extravasation.}, journal = {The Annals of pharmacotherapy}, volume = {44}, number = {5}, pages = {922-925}, doi = {10.1345/aph.1M636}, pmid = {20371757}, issn = {1542-6270}, mesh = {Adult ; Antibiotics, Antineoplastic/administration & dosage/*adverse effects/therapeutic use ; Chelating Agents/administration & dosage/*therapeutic use ; Doxorubicin/administration & dosage/*adverse effects/therapeutic use ; Extravasation of Diagnostic and Therapeutic Materials/diagnosis/*drug therapy ; Female ; Humans ; Razoxane/administration & dosage/*therapeutic use ; Treatment Outcome ; }, abstract = {OBJECTIVE: To describe a successful case of dexrazoxane treatment after an extravasation of doxorubicin and share a creative solution for formulary cost management.

CASE SUMMARY: A 42-year-old female diagnosed with breast cancer was receiving doxorubicin as adjuvant treatment. The patient recently underwent a right mastectomy for a 3-centimeter grade 3 invasive ductal carcinoma. Three of 20 lymph nodes were positive, and the patient was stage 2B at presentation, with an estrogen receptor/progesterone receptor-positive and HER-2/neu-negative tumor. At an outside hospital, the patient was receiving doxorubicin through an infusion port when extravasation was noted after approximately 15 mL had been infused. She was transferred to Riverside Methodist Hospital and dexrazoxane treatment was initiated within 6 hours after extravasation. She received a full 3-day course of dexrazoxane treatment without complication and was discharged home. Significant delays in chemotherapy administration were avoided, and the patient successfully completed her planned chemotherapy course.

DISCUSSION: Dexrazoxane has the potential to minimize tissue damage and treatment delays after an anthracycline extravasation. Although dexrazoxane is commercially marketed for 2 separate treatment indications, Totect is the Food and Drug Administration-approved product for anthracycline extravasations. Facilities administering anthracyclines should proactively resolve how to obtain, process, prepare, and administer this antidote to a patient within 6 hours of an extravasation event. Developing a preprinted chemotherapy extravasation order may facilitate the incorporation of the most recent Oncology Nursing Society guidelines to utilize dexrazoxane for an anthracycline extravasation. Cost sharing with other institutions may offer a creative solution to lessen the financial impact of stocking dexrazoxane therapy.

CONCLUSIONS: Ensuring expedient treatment and accessibility to dexrazoxane therapy after an anthracycline extravasation is critical to the success of the treatment. All facilities utilizing anthracycline chemotherapy should purchase dexrazoxane or secure agreements with other facilities to guarantee the administration of this medication should extravasation occur.}, } @article {pmid20354817, year = {2011}, author = {Barısık, NO and Keser, SH and Gul, AE and Sensu, S and Kandemir, NO and Kucuk, HF and Gumus, M and Karadayı, N}, title = {The value of COX-2 expression in the prognostic parameters of invasive ductal carcinoma of the breast.}, journal = {Medical oncology (Northwood, London, England)}, volume = {28}, number = {3}, pages = {703-708}, pmid = {20354817}, issn = {1559-131X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cyclooxygenase 2/*biosynthesis ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis/biosynthesis ; Receptors, Estrogen/analysis/biosynthesis ; Receptors, Progesterone/analysis/biosynthesis ; }, abstract = {Cyclooxygenase is an enzyme that changes the immune response to malign cells and catalyzes prostaglandins that may have an impact on cell proliferation. The purpose of this study was to examine the relation between established clinicopathological parameters in breast carcinomas and COX-2 protein expression. COX-2, estrogen receptor (ER), progesterone receptor (PR) and c-erB-2 primary antibodies were assessed in the slides prepared from the paraffin blocks of 62 invasive ductal carcinoma cases. The relation between ER, PR, and c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age were evaluated. The results were analyzed statistically. Cytoplasmic COX-2 expression was seen in 75.8% of all breast carcinomas. In both univariate and multivariate logistic regression analysis, there was a positive correlation between COX-2 expression and negative ER status, respectively (P=0.0173) (P=0.016). There was any statistically significant relation between PR positivity, c-erbB-2 positivity, histological grade, nuclear grade, lymphovascular invasion, tumor diameter, lymph node positivity, metastasis, and age (P≥0.05). Given that there was found a statistically significant relation between COX-2 expression and negative ER status, which is considered a poor prognostic parameter, suggests that COX-2 expression can have a place among the other prognostic parameters of breast carcinoma.}, } @article {pmid20339264, year = {2010}, author = {Tozaki, M and Fukuma, E and Suzuki, T and Hoshi, K}, title = {Ultrasound-guided cryoablation of invasive ductal carcinoma inside the MR room.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {9}, number = {1}, pages = {31-36}, doi = {10.2463/mrms.9.31}, pmid = {20339264}, issn = {1880-2206}, mesh = {Aged ; Architecture ; Breast Neoplasms/diagnostic imaging/pathology/*surgery ; Carcinoma/diagnostic imaging/pathology/*surgery ; Cryosurgery/*instrumentation/*methods ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging/instrumentation/methods ; Mammary Glands, Human/pathology/surgery ; Prone Position ; Ultrasonography, Mammary/*instrumentation/*methods ; }, abstract = {One disadvantage of ultrasound (US)-guided cryoablation of breast cancer is the difficulty in visualizing the area behind the ice ball because of acoustic shadowing. We performed US-guided cryoablation with the patient in prone position inside the MR room. The lumpectomy specimen after cryoablation revealed dense fibrosis without residual viable cancer cells. The combination of needle insertion under US guidance with planning and verification using magnetic resonance imaging may be a feasible and promising treatment protocol.}, } @article {pmid20332474, year = {2010}, author = {Shimizu, T and Hirano, A and Watanabe, O and Kinoshita, J and Kimura, K and Kamimura, M and Domoto, K and Kim, N and Ogawa, K and Fujibayashi, M}, title = {Successful neoadjuvant therapy with trastuzumab, paclitaxel and epirubicin for an elderly patient with inflammatory breast cancer.}, journal = {Anticancer research}, volume = {30}, number = {2}, pages = {581-585}, pmid = {20332474}, issn = {1791-7530}, mesh = {Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Cyclophosphamide/administration & dosage ; Epirubicin/administration & dosage ; Female ; Humans ; *Neoadjuvant Therapy ; Paclitaxel/administration & dosage ; Remission Induction ; Trastuzumab ; Treatment Outcome ; }, abstract = {A 75-year old woman presented with diffuse left breast enlargement, redness, edema, and a firm palpable lymph node with skin fixation in the left axilla. The tumor was diagnosed as invasive ductal carcinoma with a strongly positive human epidermal growth factor receptor 2 (HER2) score (3+). She was diagnosed as having inflammatory breast cancer (IBC) (T4d N2M0, stage IIIb). The patient received primary systemic chemotherapy with 4 courses of epirubicin 75 mg/m(2) and cyclophosphamide 500 mg/m(2) every three weeks, then 12 courses of paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (initially 4 mg/kg) weekly. Six months after the start of chemotherapy, a left modified radical mastectomy with axillary dissection was performed. No cancer cells in the breast specimen and no metastases to the axillary nodes were observed, so the therapeutic effect was determined as a pathological complete response (pCR). This report suggests that combination therapy with epirubicin and cyclophosphamide followed by trastuzumab and paclitaxel was useful for HER2-positive IBC.}, } @article {pmid20307407, year = {2010}, author = {Omre, AH}, title = {Bluetooth low energy: wireless connectivity for medical monitoring.}, journal = {Journal of diabetes science and technology}, volume = {4}, number = {2}, pages = {457-463}, doi = {10.1177/193229681000400227}, pmid = {20307407}, issn = {1932-2968}, mesh = {Blood Glucose/analysis ; Cell Phone ; Computer Communication Networks/economics/instrumentation ; Costs and Cost Analysis ; Diabetes Mellitus/blood/therapy ; Home Care Services ; Humans ; Licensure ; Monitoring, Physiologic/economics/*instrumentation/methods ; Oxygen/blood ; Radio Waves ; Signal Transduction ; Telemedicine/*instrumentation/methods ; Telemetry/*instrumentation/methods ; United States ; United States Department of Agriculture ; }, abstract = {Electronic wireless sensors could cut medical costs by enabling physicians to remotely monitor vital signs such as blood pressure, blood glucose, and blood oxygenation while patients remain at home. According to the IDC report "Worldwide Bluetooth Semiconductor 2008-2012 Forecast," published November 2008, a forthcoming radio frequency communication ("wireless connectivity") standard, Bluetooth low energy, will link wireless sensors via radio signals to the 70% of cell phones and computers likely to be fitted with the next generation of Bluetooth wireless technology, leveraging a ready-built infrastructure for data transmission. Analysis of trends indicated by this data can help physicians better manage diseases such as diabetes. The technology also addresses the concerns of cost, compatibility, and interoperability that have previously stalled widespread adoption of wireless technology in medical applications.}, } @article {pmid20304650, year = {2010}, author = {Yu, JI and Choi, DH and Park, W and Huh, SJ and Cho, EY and Lim, YH and Ahn, JS and Yang, JH and Nam, SJ}, title = {Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study.}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {3}, pages = {231-237}, doi = {10.1016/j.breast.2010.01.020}, pmid = {20304650}, issn = {1532-3080}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/*mortality/*pathology/therapy ; Carcinoma, Papillary/*mortality/*pathology/therapy ; Case-Control Studies ; Cohort Studies ; Combined Modality Therapy ; Female ; Humans ; Middle Aged ; Prognosis ; Survival Rate ; Treatment Failure ; }, abstract = {PURPOSE: We designed this study to identify differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma (IDC) in patients with breast cancer.

EXPERIMENTAL DESIGN: We identified 72 cases of IMPC who were diagnosed between 1999 and 2007 at the Samsung Medical Center. These patients were matched with 144 controls who were diagnosed with IDC during the same period. Exact matches were made for age (+/-3 years), pathologic tumour and node stage, and treatment methods (surgery and radiation therapy).

RESULTS: The median follow-up period was 45 months (13-116) for IMPC and 50 months (16-122) for IDC. Lymphovascular invasion (LVI, p<0.0001), axillary lymph node extracapsular extension (ECE, p=0.001) and high nuclear grade (p=0.032) were more frequently detected in patients with IMPC. During the follow-up period, treatment failed in 15 IMPC patients (20.8%) and in 26 IDC patients (18.1%). Loco-regional recurrences developed in 11 IMPC patients (15.3%) and eight IDC patients (5.6%). Importantly, of 57 IMPC patients who had positive axillary nodes, seven patients (12.3%) had axilla and/or supraclavicular recurrence. Therefore, at 5 years, the loco-regional recurrence-free survival was 79.1% in the IMPC patients vs. 93.3% in the IDC patients (p=0.0024).

CONCLUSION: Our study showed that IMPC is associated with LVI, ECE, high nuclear grade, and a greater degree of loco-regional recurrence, especially in the axilla and supraclavicular areas. Therefore, axillary and supraclavicular radiation therapy should be considered in IMPC patients with axillary node metastasis.}, } @article {pmid20302026, year = {2009}, author = {Yagmurdur, MC and Atac, FB and Uslu, N and Ekici, Y and Verdi, H and Ozdemir, BH and Moray, G and Haberal, M}, title = {Clinical importance of vitamin D receptor gene polymorphism in invasive ductal carcinoma.}, journal = {International surgery}, volume = {94}, number = {4}, pages = {304-309}, pmid = {20302026}, issn = {0020-8868}, mesh = {Alleles ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics ; Diagnostic Imaging ; Female ; Genotype ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Metastasis/genetics ; Neoplasm Recurrence, Local/genetics ; Neoplasm Staging ; *Polymorphism, Genetic ; Receptors, Calcitriol/*genetics ; Retrospective Studies ; Statistics, Nonparametric ; Survival Rate ; }, abstract = {In this study, we aimed to investigate the clinical importance of the vitamin D receptor gene polymorphism in invasive ductal breast cancer. All patients included in the study had clinical T1-2, N0-M0 invasive ductal carcinoma. Patients' demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. Vitamin D receptor B genotype frequencies in the patient group (P > 0.05) were as follows: B/b, 43 (77%); B/B, 13 (23%). In conclusion, the vitamin D receptor gene B allele does not seem to be related to local recurrence and distant metastasis of invasive ductal cancer of the breast.}, } @article {pmid20238193, year = {2010}, author = {Slart, RH and Tio, RA and van der Vleuten, PA and Willems, TP and Lubbers, DD and Dierckx, RA and van Veldhuisen, DJ}, title = {Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology}, volume = {17}, number = {3}, pages = {479-485}, pmid = {20238193}, issn = {1532-6551}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Cardiomyopathy, Dilated/diagnostic imaging/drug therapy/*physiopathology ; *Coronary Circulation ; Dipyridamole/pharmacology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; *Myocardial Contraction ; Myocardium/metabolism ; Oxygen Consumption ; Positron-Emission Tomography ; Radiopharmaceuticals ; *Ventricular Function, Left ; }, abstract = {BACKGROUND: In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance.

METHODS: Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF.

RESULTS: Sixteen patients were included (age 47.9 +/- 11.5 years; 12 males, LVEF 28.6 +/- 8.4%). Seven patients showed improved LVEF (9.7 +/- 3.1%), and nine patients did not show improved LVEF (-3.4 +/- 3.9%). MPR improved significantly in responders (1.56 +/- .23 to 1.93 +/- .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- .70 to 1.61 +/- .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns).

CONCLUSION: In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve.}, } @article {pmid20236691, year = {2010}, author = {Gonzalez, LO and Junquera, S and del Casar, JM and González, L and Marín, L and González-Reyes, S and Andicoechea, A and González-Fernández, R and González, JM and Pérez-Fernández, R and Vizoso, FJ}, title = {Immunohistochemical study of matrix metalloproteinases and their inhibitors in pure and mixed invasive and in situ ductal carcinomas of the breast.}, journal = {Human pathology}, volume = {41}, number = {7}, pages = {980-989}, doi = {10.1016/j.humpath.2009.08.027}, pmid = {20236691}, issn = {1532-8392}, mesh = {Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinases/*biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Tissue Inhibitor of Metalloproteinases/*biosynthesis ; }, abstract = {We assessed differences in the patterns of expression of matrix metalloproteases and their inhibitors (tissue inhibitors of metalloproteases) in ductal carcinoma in situ alone and admixed with invasive ductal carcinomas (n = 40), as well as in pure invasive ductal carcinomas (n = 40), immunohistochemically and using tissue arrays. The invasive ductal carcinoma components showed higher expression of matrix metalloprotease-9 and -13 than did the admixed ductal carcinoma in situ, whereas stromal fibroblasts of the invasive components showed higher expression of matrix metalloprotease-2, -7, -9, -13, and -14 and tissue inhibitor of metalloprotease-1 and -3 than did fibroblasts around the neoplastic ducts of the admixed ductal carcinoma in situ. Expression of matrix metalloprotease-14 and tissue inhibitor of metalloprotease-3 was significantly higher in the mononuclear inflammatory cells of the invasive components. By contrast, matrix metalloprotease-1 expression was significantly higher in stromal cells of the ductal carcinoma in situ admixed with invasive ductal carcinoma. The pure invasive ductal carcinomas had significantly higher expression of matrix metalloprotease-1, -9, -11, and -14 and tissue inhibitor of metalloprotease-1 and -3 than the invasive ductal carcinomas admixed with ductal carcinoma in situ. Our findings indicate a significant association of matrix metalloprotease expression by the periductal stromal cells of the ductal carcinoma in situ component of mixed tumors and the occurrence of distant metastasis. Our data suggest that the molecular matrix metalloprotease/tissue inhibitor of metalloprotease profile can contribute to better characterization of early breast carcinomas.}, } @article {pmid20236684, year = {2010}, author = {Okada, N and Hasebe, T and Iwasaki, M and Tamura, N and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kanai, Y and Kinoshita, T}, title = {Metaplastic carcinoma of the breast.}, journal = {Human pathology}, volume = {41}, number = {7}, pages = {960-970}, doi = {10.1016/j.humpath.2009.11.013}, pmid = {20236684}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/diagnosis/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/*pathology/therapy ; Carcinoma, Lobular/diagnosis/*pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Metaplasia ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Young Adult ; }, abstract = {The purposes of this study were to investigate whether the biological characteristics or outcomes of patients with metaplastic carcinoma, invasive ductal carcinoma, or invasive lobular carcinoma of the breast differ; to determine whether the metaplastic carcinoma subtypes have similar malignant potentials; and to identify accurate predictors of outcome in patients with metaplastic carcinoma. The subject comprised 6137 invasive ductal carcinoma patients, 301 invasive lobular carcinoma patients, and 46 metaplastic carcinoma patients of the breast. The metaplastic carcinomas were classified according to the World Health Organization classification. Multivariate analyses clearly demonstrated that the metaplastic carcinoma patients had a significantly poorer outcome than the invasive ductal carcinoma patients or the invasive lobular carcinoma patients independent of the nodal status or age not exceeding 39 years, whereas patients with triple-negative metaplastic carcinomas or triple-negative invasive lobular carcinomas had a poorer outcome than those with triple-negative invasive ductal carcinomas. Although no significant differences in clinical outcome were observed among the metaplastic carcinoma subtypes in multivariate analyses, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant outcome predictors for metaplastic carcinoma patients. In conclusion, the results of this study clearly demonstrated that metaplastic carcinoma is more aggressive than invasive ductal carcinoma or invasive lobular carcinoma. Although the metaplastic carcinoma subtypes had no prognostic significance, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant predictors of outcome among metaplastic carcinoma patients.}, } @article {pmid20232453, year = {2010}, author = {Razek, AA and Gaballa, G and Denewer, A and Nada, N}, title = {Invasive ductal carcinoma: correlation of apparent diffusion coefficient value with pathological prognostic factors.}, journal = {NMR in biomedicine}, volume = {23}, number = {6}, pages = {619-623}, doi = {10.1002/nbm.1503}, pmid = {20232453}, issn = {1099-1492}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology/secondary ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Prognosis ; Prospective Studies ; Young Adult ; }, abstract = {The aim of this study was to correlate the apparent diffusion coefficient (ADC) value of invasive ductal carcinoma with pathological prognostic factors. A prospective study was conducted on 59 untreated female patients (mean age 46 years) with invasive ductal carcinoma. All patients were examined at 1.5 Tesla using dedicated bilateral breast coil. They underwent diffusion weighted MR imaging of the breast using a single shot echo planar imaging with a b-factor of 200 and 400 sec/mm2. Apparent diffusion coefficient (ADC) maps were reconstructed. The ADC value of the breast cancer was calculated and correlated with the pathologic prognostic factors (tumor size, grade and lymph nodes). The mean ADC values of invasive ductal carcinoma were significantly lower in patients with high grade, large breast cancer as well as those with axillary lymph nodes metastasis in a statistically significant way (p = 0.001 for the three factors). The mean ADC value of invasive ductal carcinoma was correlated with histologic grade (r = -0.675, p = 0.001), tumor size (r = 0.504, p = 0.001) and showed lower ADC values with positive lymph node metastasis. Apparent diffusion coefficient value is correlated with pathological parameters of invasive ductal carcinoma. The lower ADC values are associated with higher histological grade, larger tumor size and presence of axillary lymph nodes. So, the ADC value can be considered as a promising prognostic parameter that may identify highly aggressive breast cancer.}, } @article {pmid20231284, year = {2010}, author = {Sun, XE and Sharling, L and Muthalagi, M and Mudeppa, DG and Pankiewicz, KW and Felczak, K and Rathod, PK and Mead, J and Striepen, B and Hedstrom, L}, title = {Prodrug activation by Cryptosporidium thymidine kinase.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {21}, pages = {15916-15922}, pmid = {20231284}, issn = {1083-351X}, support = {AI082617/AI/NIAID NIH HHS/United States ; T32 GM007596/GM/NIGMS NIH HHS/United States ; U01 AI075466/AI/NIAID NIH HHS/United States ; R56 AI082617/AI/NIAID NIH HHS/United States ; 2T32GM007596/GM/NIGMS NIH HHS/United States ; U01AI75466/AI/NIAID NIH HHS/United States ; R01 AI055268/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antiprotozoal Agents/*pharmacology ; Cell Line, Tumor ; Cryptosporidiosis/*drug therapy/enzymology ; Cryptosporidium parvum/*enzymology/genetics ; Disease Models, Animal ; Floxuridine/pharmacology ; Genome, Protozoan ; Humans ; Mice ; Mice, Knockout ; Prodrugs/*pharmacology ; Protozoan Proteins/*antagonists & inhibitors/genetics/metabolism ; Pyrimidines/metabolism/pharmacology ; Recombinant Proteins/antagonists & inhibitors/genetics/metabolism ; Thymidine Kinase/*antagonists & inhibitors/genetics/metabolism ; }, abstract = {Cryptosporidium spp. cause acute gastrointestinal disease that can be fatal for immunocompromised individuals. These protozoan parasites are resistant to conventional antiparasitic chemotherapies and the currently available drugs to treat these infections are largely ineffective. Genomic studies suggest that, unlike other protozoan parasites, Cryptosporidium is incapable of de novo pyrimidine biosynthesis. Curiously, these parasites possess redundant pathways to produce dTMP, one involving thymidine kinase (TK) and the second via thymidylate synthase-dihydrofolate reductase. Here we report the expression and characterization of TK from C. parvum. Unlike other TKs, CpTK is a stable trimer in the presence and absence of substrates and the activator dCTP. Whereas the values of k(cat) = 0.28 s(-1) and K(m)(,ATP) = 140 microm are similar to those of human TK1, the value of K(m)(thymidine) = 48 microm is 100-fold greater, reflecting the abundance of thymidine in the gastrointestinal tract. Surprisingly, the antiparasitic nucleosides AraT, AraC, and IDC are not substrates for CpTK, indicating that Cryptosporidium possesses another deoxynucleoside kinase. Trifluoromethyl thymidine and 5-fluorodeoxyuridine are good substrates for CpTK, and both compounds inhibit parasite growth in an in vitro model of C. parvum infection. Trifluorothymidine is also effective in a mouse model of acute disease. These observations suggest that CpTK-activated pro-drugs may be an effective strategy for treating cryptosporidiosis.}, } @article {pmid20229034, year = {2010}, author = {Zhou, D and Cheng, SQ and Ji, HF and Wang, JS and Xu, HT and Zhang, GQ and Pang, D}, title = {Evaluation of protein pigment epithelium-derived factor (PEDF) and microvessel density (MVD) as prognostic indicators in breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {136}, number = {11}, pages = {1719-1727}, pmid = {20229034}, issn = {1432-1335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/metabolism/mortality/*pathology ; Cohort Studies ; Disease Progression ; Eye Proteins/*genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; *Microcirculation ; Middle Aged ; Neoplasm Metastasis/pathology ; Neoplasm Staging ; Neovascularization, Pathologic/metabolism/*pathology ; Nerve Growth Factors/*genetics/metabolism ; Prognosis ; Serpins/*genetics/metabolism ; Survival Analysis ; Survival Rate ; }, abstract = {PURPOSE: Angiogenesis, which plays an important role in tumor growth and metastasis, is regulated by a balance between angiogenic stimulators and inhibitors. Pigment epithelium-derived factor (PEDF), a secreted glycoprotein is an important inhibitor of angiogenesis. Although the precise mechanisms by which PEDF exerts its actions remain poorly understood, there is growing evidence supporting the role of PEDF as a candidate antitumor agent. In this study, we investigated the role of PEDF in breast cancer.

METHODS: We investigated the correlation of PEDF protein levels with cancer progression and prognosis in patients with invasive ductal breast cancer (IDC). We used immunohistochemistry in a cohort of 119 breast cancer patients to examine the expression of PEDF protein with an anti-PEDF antibody and to measure the microvessel density (MVD) with an anti-CD34 antibody.

RESULTS: PEDF was an endogenous inhibitor of angiogenesis in endothelial cells. Decreased intratumoral expression of PEDF was associated with a higher microvessel density (MVD), a more metastatic phenotype, and poorer clinical outcome. PEDF was positive in 43.7% patients. Patients with low PEDF expression had a significantly higher MVD count when compared with patients with high PEDF expression. In univariate and multivariate analysis, PEDF was an independent prognostic factor.

CONCLUSION: The inverse correlation between PEDF expression and MVD in human breast cancer suggests that low PEDF expression is associated with angiogenesis in breast cancer. PEDF expression is therefore a potentially useful prognostic marker for breast cancer.}, } @article {pmid20224728, year = {2010}, author = {Behjatnia, B and Sim, J and Bassett, LW and Moatamed, NA and Apple, SK}, title = {Does size matter? Comparison study between MRI, gross, and microscopic tumor sizes in breast cancer in lumpectomy specimens.}, journal = {International journal of clinical and experimental pathology}, volume = {3}, number = {3}, pages = {303-309}, pmid = {20224728}, issn = {1936-2625}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*pathology/surgery ; Carcinoma, Lobular/diagnosis/*pathology/surgery ; Diagnostic Errors/prevention & control ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental ; Microscopy/*methods ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {Size of breast cancer is essential in staging cancer to determine type and extent of patient management. This study was conducted to assess accuracy in estimating tumor size by MRI and gross using microscopy as gold standard. A retrospective study was done on 33 patients, 30-75 years, who underwent MRI of breasts with subsequent lumpectomy, 2002-2006, for invasive breast cancer. Size of lesion(s) on MRI and gross were compared with histological size. Of 37 lesions, 27 (73%) were invasive ductal (IDC) and 10 (27%) invasive lobular carcinoma (ILC). Tumor size by MRI matched histological size in 3%, underestimated 27%, and overestimated 70% of cases. Tumor size by gross matched histological size in 22%, underestimated 57%, and overestimated 22% of cases. MRI as an imaging modality and gross pathology both have significant limitations in measuring tumor size particularly in cases of invasive breast carcinoma. Random sectioning of lumpectomy specimen in invasive breast carcinoma may result in inaccurate staging of tumor by leading to false impression of tumor size and multi-focality and/or multi-centricity of tumor particularly in cases of ILC. Microscopic measurements of tumor size are necessary for accurate T-staging and recommended for appropriate patient management.}, } @article {pmid20220513, year = {2010}, author = {Han, B and Suleman, K and Wang, L and Siddiqui, J and Sercia, L and Magi-Galluzzi, C and Palanisamy, N and Chinnaiyan, AM and Zhou, M and Shah, RB}, title = {ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia.}, journal = {The American journal of surgical pathology}, volume = {34}, number = {4}, pages = {478-485}, doi = {10.1097/PAS.0b013e3181d6827b}, pmid = {20220513}, issn = {1532-0979}, support = {P50CA69568/CA/NCI NIH HHS/United States ; R01 CA102872/CA/NCI NIH HHS/United States ; UO1 CA111275-01/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; Biopsy, Needle ; Carcinoma, Ductal/genetics/*pathology/surgery ; *Chromosome Aberrations ; Diagnosis, Differential ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Prostatic Intraepithelial Neoplasia/genetics/*pathology/surgery ; Prostatic Neoplasms/genetics/*pathology/surgery ; Proto-Oncogene Proteins c-ets/*genetics ; }, abstract = {BACKGROUND: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone.

METHODS: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24).

RESULTS: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified.

CONCLUSIONS: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.}, } @article {pmid20210803, year = {2010}, author = {Hsiao, YH and Lien, HC and Hwa, HL and Kuo, WH and Chang, KJ and Hsieh, FJ}, title = {SPARC (osteonectin) in breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma.}, journal = {The breast journal}, volume = {16}, number = {3}, pages = {305-308}, doi = {10.1111/j.1524-4741.2009.00899.x}, pmid = {20210803}, issn = {1524-4741}, mesh = {Breast Neoplasms/*chemistry/mortality/pathology ; Carcinoma, Ductal, Breast/*chemistry/mortality/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Osteonectin/*analysis/physiology ; Proportional Hazards Models ; }, abstract = {The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Secreted protein acidic and rich in cystein was not expressed in benign breast phylloides and all benign breast tumors, while expressed in 17.2% of IDC, 85% of metaplastic carcinoma of the breast (MCB), and all malignant breast phylloides. Secreted protein acidic and rich in cystein was strongly expressed in mesenchymal components of MCB and expression levels in epithelial components were variable. The correlation of positive expression of SPARC and poor long-term survival in IDC is significant (p = 0.004). Individuals with positive SPARC expression had 2.34 times higher hazard of death compared with those with negative SPARC expression after adjusting for factors including positive lymph node, TNM tumor stage, estrogen receptor, and progesterone receptor. Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC.}, } @article {pmid20209373, year = {2010}, author = {Périssé, G and Medronho, Rde A and Escosteguy, CC}, title = {[Urban space and mortality from ischemic heart disease in the elderly in Rio de Janeiro].}, journal = {Arquivos brasileiros de cardiologia}, volume = {94}, number = {4}, pages = {463-471}, doi = {10.1590/s0066-782x2010005000009}, pmid = {20209373}, issn = {1678-4170}, mesh = {Age Distribution ; Aged ; Brazil/epidemiology ; Cause of Death ; Ecological and Environmental Phenomena ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*mortality ; Sex Distribution ; Socioeconomic Factors ; Statistics, Nonparametric ; Urban Population/*statistics & numerical data ; }, abstract = {BACKGROUND: Cardiovascular diseases are the leading cause of death in Brazil, especially among the elderly. In the city of Rio de Janeiro (RJC), ischemic heart disease (IHD) is the predominant cause of mortality. Studies show an association between the process of urbanization, socioeconomic conditions and changes in lifestyle with the occurrence of IHD.

OBJECTIVE: To describe the geographical distribution of the IHD mortality rates in the elderly of RJC in 2000 and its correlation with socioeconomic variables.

METHODS: This was an ecological study with a spatial analysis of the distribution of the IHD mortality rates in the elderly residing in RJC in 2000, standardized by gender and age, and its correlation with socioeconomic variables from the demographic census.

RESULTS: There were no strong correlations between the socioeconomic variables and IHD mortality in the elderly in the districts. Some correlations, albeit weak, showed an association between higher socioeconomic status and higher mortality. After correcting the IHD mortality rate by adding ill-defined causes (IDC) of death, an association between low socioeconomic status and higher mortality from IHD was observed. The study showed spatial dependence for socioeconomic variables, but not for mortality from IHD.

CONCLUSION: The spatial dependence observed in economic variables shows that the urban space in MRJ, although heterogeneous, has a certain amount of discrimination in the districts. Some correlations between IHD and socioeconomic variables were opposite to those found in the literature, and this may be partly related to the proportion of IDC, or to the exclusive profile of this age group.}, } @article {pmid20208478, year = {2010}, author = {Hasebe, T and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Kinoshita, T and Tsuda, H}, title = {p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci in invasive ductal carcinoma of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {5}, pages = {662-672}, doi = {10.1038/modpathol.2010.47}, pmid = {20208478}, issn = {1530-0285}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology/therapy ; Carcinoma, Ductal, Breast/*metabolism/pathology/therapy ; Chemotherapy, Adjuvant ; Estrogen Receptor alpha/metabolism ; Female ; Fibroblasts/*metabolism/pathology ; Fibrosis/metabolism/pathology ; Humans ; Immunohistochemistry ; Mastectomy ; Middle Aged ; Prognosis ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The purpose of this study was to determine whether p53 protein expression in tumor-stromal fibroblasts forming fibrotic foci is a significant outcome predictor, similar to p53 protein expression in tumor-stromal fibroblasts not forming fibrotic foci, and whether the combined assessment of p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci served as an important outcome predictor among 1039 patients with invasive ductal carcinoma of the breast. We analyzed the outcome predictive power of the Allred score risk classification for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci using multivariate analyses with well-known clinicopathological factors. The Allred score risk classifications for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci were superior to the Allred scores for p53 in tumor-stromal fibroblasts not forming fibrotic foci alone for accurately predicting the tumor-related death of patients with invasive ductal carcinoma when examined using multivariate analyses. The Allred score risk classification for p53 in tumor-stromal fibroblasts forming and not forming fibrotic foci significantly increased the hazard rates for tumor recurrence and tumor-related death independent of the UICC pTNM stage in the multivariate analyses. These results indicated that the Allred score risk classification based on the combined assessment of p53 expression in tumor-stromal fibroblasts forming and not forming fibrotic foci is a very useful outcome predictor among patients with invasive ductal carcinoma.}, } @article {pmid20204257, year = {2010}, author = {Vilaseca, MA and Lambruschini, N and Gómez-López, L and Gutiérrez, A and Fusté, E and Gassió, R and Artuch, R and Campistol, J}, title = {Quality of dietary control in phenylketonuric patients and its relationship with general intelligence.}, journal = {Nutricion hospitalaria}, volume = {25}, number = {1}, pages = {60-66}, pmid = {20204257}, issn = {0212-1611}, mesh = {Adolescent ; Adult ; Aging/physiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Infant ; *Intelligence ; Longitudinal Studies ; Male ; Phenylketonurias/*diet therapy/*psychology ; Young Adult ; }, abstract = {OBJECTIVES: Assessment of the quality of dietary treatment of phenylketonuria (PKU) patients and investigation of its relationship with the general intelligence of the patients.

METHODS: Cross-sectional and longitudinal study of 105 PKU treated patients. The index of dietary control (IDC) was calculated as the phenylalanine (Phe) data reduction in half-year medians and the mean of all medians throughout the patient's life. We calculated four different IDCs related to age: IDC-A (< 6 years), IDC-B (6-12 years), IDC-C (13-18 years) and IDC-D (> 18 years). To evaluate the fluctuation of Phe values we calculated the standard error of the estimate of the regression of Phe concentration over age. Development quotient was calculated with the Brunet-Lezine test (< 4 years). Intelligence quotient was evaluated with the Kaufman Bit Intelligence Test (K-Bit), Wechsler Intelligence Scale for Children-Revised (WISC-R) and Wechsler Adult Intelligence Scale Third Edition (WAIS III).

RESULTS: Cross-sectional study: The IDC in age groups were significantly different and so were the number of patients with good, acceptable and poor IDC related to age (p < 0.001). Sampling frequency was good in 72, acceptable in 23 and poor in 10 patients. The general intelligence (101 +/- 10) correlated negatively with the IDC (p < 0.0001) and Phe fluctuations (p < 0.004). Longitudinal study: Significant differences were observed between the IDC through the patients' lifetime except in the adolescent/adult period.

CONCLUSIONS: 85% of PKU patients showed good/acceptable quality of dietary control. General intelligence correlates with the IDC at all ages, which highlights the importance of good control to achieve good prognosis.}, } @article {pmid20193454, year = {2009}, author = {Hua, BL and Fu, XG and Hu, WH and Yin, L and Kang, XL and Li, HA and Jiang, JF and Li, F}, title = {[Notch1 mRNA and protein expression in human breast cancer and normal mammary gland tissues].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {12}, pages = {806-809}, pmid = {20193454}, issn = {0529-5807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Mammary Glands, Human/*metabolism ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/metabolism ; Receptor, Notch1/genetics/*metabolism ; }, abstract = {OBJECTIVE: To explore the Notch1 mRNA and protein expression in human breast cancers and normal mammary tissues, and their relationship with the clinical indicators of breast cancers were analyzed.

METHODS: Notch1 gene of human breast invasive ductal carcinoma (IDC) and normal mammary gland tissues were amplified by RT-PCR, and the expression of Notch1 protein was detected by immunohistochemical Streptavidin-Biotin Complex (SP) stain in 60 IDC, 30 ductal carcinoma in situ (DCIS) and 60 normal mammary tissues.

RESULTS: Notch1 gene of human IDC and normal mammary tissues both could express in a transcription level; the positive rates of Notch1 protein expression in normal mammary tissues and DCIS were 55% and 70%. Respectively, which did not differ statistically (P > 0.05), while the positive rate in IDC was 90%, significantly higher than that of the normal mammary tissues and DCIS (P < 0.05). The high expression of Notch1 protein in IDC correlate significantly with lymph node metastasis, pathological grades and TNM stages.

CONCLUSIONS: Notch1 protein was over expressed in breast IDC. A high Notch1 protein expression is considered associating with the evolution and malignant transformation of the breast tumor. The expression of Notch1 gene maybe impact the effect of on the progression of breast cancers.}, } @article {pmid20191218, year = {2009}, author = {Oliveira, VM and Ribeiro, Lde S and Rossi, LM and Silva, MA and Aldrighi, JM and Bagnoli, F and Rinaldi, JF and Aoki, T}, title = {[Aromatase expression in invasive and in situ ductal carcinoma present in the same breast].}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {55}, number = {6}, pages = {651-655}, doi = {10.1590/s0104-42302009000600008}, pmid = {20191218}, issn = {0104-4230}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aromatase/*analysis ; Breast Neoplasms/*enzymology/pathology/surgery ; Carcinoma, Ductal, Breast/*enzymology/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; Neoplasm Proteins/*analysis ; Neoplasm Staging ; Retrospective Studies ; }, abstract = {OBJECTIVE: to evaluate the expression of aromatase in simultaneously invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS).

METHODS: forty-five surgical samples were obtained from mastectomy and quadrantectomy with simultaneous IDC and DCIS of stage I and II patients. Aromatase was evaluated using antibodies anti-aromatase and the samples classified in accordance with the number and intensity of stained cells.

RESULTS: Aromatase was expressed positively in 32(71%) and negatively in 13(29%) of the cases in the IDC. The same results were obtained in the DCIS showing a perfect positive correlation. In the normal epithelium,aromatase was positive in 19(42.2%) and negative in 26 (57.8%) and a positive correlation, statistically significant was obtained when compared with IDC and DCIS(p<0.01). Concerning the normal stroma, positivity was only 7 (15.5%) showing no correlation with aromatase expression. Aromatase was positive in 36(80%) of the tumor stroma and this result was statistically significant as in the IDC and DCIS. Comparing results of aromatase expression with nuclear grade, histological grade, tumor size and age no difference was found.

CONCLUSION: our results demonstrated high correlation between aromatase expression in IDC, DCIS, normal epithelium and tumor stroma showing a possible autocrine and paracrine mechanism of this enzyme in breast cancer.}, } @article {pmid20191033, year = {2010}, author = {Park, S and Koo, J and Kim, JH and Yang, WI and Park, BW and Lee, KS}, title = {Clinicopathological characteristics of mucinous carcinoma of the breast in Korea: comparison with invasive ductal carcinoma-not otherwise specified.}, journal = {Journal of Korean medical science}, volume = {25}, number = {3}, pages = {361-368}, pmid = {20191033}, issn = {1598-6357}, mesh = {Adenocarcinoma, Mucinous/diagnosis/genetics/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/classification/diagnosis/genetics/*pathology ; Carcinoma, Ductal/diagnosis/genetics/*pathology ; Disease-Free Survival ; Female ; Genes, erbB-2 ; Humans ; Korea ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Young Adult ; }, abstract = {Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.}, } @article {pmid20182345, year = {2010}, author = {Shah, RB and Magi-Galluzzi, C and Han, B and Zhou, M}, title = {Atypical cribriform lesions of the prostate: relationship to prostatic carcinoma and implication for diagnosis in prostate biopsies.}, journal = {The American journal of surgical pathology}, volume = {34}, number = {4}, pages = {470-477}, doi = {10.1097/PAS.0b013e3181cfc44b}, pmid = {20182345}, issn = {1532-0979}, mesh = {Adenocarcinoma/*pathology/surgery ; Biopsy ; Biopsy, Needle ; Humans ; Male ; Prostate/*pathology/surgery ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; }, abstract = {Atypical cribriform lesions of the prostate (ACL) are cribriform glands lined by cytologically malignant cells with partial or complete basal cell lining. They represent cribriform high-grade PIN (cribriform HGPIN), which can be an isolated finding not associated with PCa (isolated ACL), or "intraductal carcinoma (IDC-P)" that is almost always associated with infiltrative high-grade prostate carcinoma (PCa) (cancer-associated ACL, ACL-PCa). We report the incidence, topographic relation to cancer, and morphologic differences of these 2 lesions in radical prostatectomy and discuss the potential biologic basis and implication for diagnosis in prostate biopsy. ACL was defined as cribriform glands comprising cytologically malignant cells that spanned the entire glandular lumens with partial or complete basal cell lining confirmed by basal cell immunostaining. ACL intermixed with, or within 3 mm from the border of infiltrative PCa was categorized as ACL-PCa and was considered to be equivalent to IDC-P. ACLs other than ACL-PCa were considered as isolated ACL and equivalent to cribriform HGPIN. These histologic features of ACL were reviewed: number of ACL/prostate gland, size, glandular contour (round, irregular, branching), architectural pattern (dense cribriform, irregular cribriform, solid), comedonecrosis, and nuclear features (round and uniform, round with varying sizes, pleomorphic, giant nuclei [6x adjacent nuclei]). In 117 consecutive radical prostatectomy specimens, ACL-PCa and isolated ACLs were found in 21 (17.9%) and 15 (12.8%), respectively. ACL-PCa was more common in PCa with Gleason score more than or equal to 7 and higher tumor volume. The isolated ACLs were more common in Gleason score 6 PCa and their incidence was not significantly different among PCa with different tumor volumes. The mean number of ACL per prostate was 23.8 for ACL-PCa and 2.4 for isolated ACL (P=0.008). The size ranged from 0.2 to 9.0 mm for ACL-PCa, and from 0.2 to 1 mm for isolated ACL. The branching contour was present in 36/43 ACL-PCa, but only in 1/23 isolated ACL (P<0.001). The dense cribriform and solid architecture were present in 6 (14.0%) and 4 (9.3%) of ACL-PCa, but none of the isolated ACLs. Comedonecrosis was present in 14/43 (32.6%) ACL-PCa, and in none of the isolated ACL (P=0.001). The pleomorphic nuclei or giant nuclei at least 6X of the adjacent nuclei, were present in 12 (27.9%) ACL-PCa, but in none of the isolated ACL (P=0.005). ACL can be found both in association with PCa or without associated infiltrative PCa. Isolated ACL is uncommon, and the overwhelming majority of ACLs is associated with high grade (GS> or =7) and high-volume PCa and represents IDC-P. Large gland size (>1 mm), large focus involving many glands (number>6), complex architecture, and high-grade nuclei are characteristic of IDC-P. However, cribriform HGPIN and IDC-P overlap at the "low grade" architectural and morphologic spectrum and are difficult to distinguish based on morphologic criteria alone. If a biopsy contains a small number of ACL glands with "low grade" morphology, it should be diagnosed as "atypical cribriform lesion, cannot distinguish between cribriform HGPIN and IDC-P" and a repeat biopsy should be strongly recommended to rule out unsampled PCa. In contrast, if a biopsy contains ACL with one or several features of large focus, architectural complexity with large branching glands, pleomorphic or giant nuclei, or comedonecrosis, the biopsy should be diagnosed as IDC-P and definitive therapy should be recommended.}, } @article {pmid20175624, year = {2010}, author = {Mikulincer, M and Shaver, PR and Bar-On, N and Ein-Dor, T}, title = {The pushes and pulls of close relationships: attachment insecurities and relational ambivalence.}, journal = {Journal of personality and social psychology}, volume = {98}, number = {3}, pages = {450-468}, doi = {10.1037/a0017366}, pmid = {20175624}, issn = {1939-1315}, mesh = {Adolescent ; Adult ; *Altruism ; Anxiety Disorders/diagnosis/psychology ; Female ; Humans ; *Interpersonal Relations ; Male ; *Motivation ; *Object Attachment ; Psychological Theory ; Young Adult ; }, abstract = {Attachment theorists have emphasized that attachment-anxious individuals are ambivalent in their relational tendencies, wishing to be close to their relationship partners but also fearing rejection. Here we report 6 studies examining the contribution of attachment anxiety and experimentally induced relational contexts (both positive and negative) to explicit and implicit manifestations of (a) attitudinal ambivalence toward a romantic partner and (b) motivational ambivalence with respect to the goals of relational closeness and distance. Attachment-anxious individuals exhibited strong attitudinal ambivalence toward a romantic partner, assessed by both explicit and implicit measures. They also exhibited strong motivational ambivalence regarding closeness (both explicit and implicit), and this motivational conflict was intensified in relational contexts that encouraged either approach or avoidance tendencies. Participants who scored relatively high on avoidant attachment proved to be implicitly ambivalent about distance issues but mainly in negative relational contexts. Several alternative interpretations of the results were considered and ruled out.}, } @article {pmid20174726, year = {2010}, author = {Atik, E and Akansu, B and Bakaris, S and Aban, N}, title = {Expression of cyclooxygenase-2 and its relation to histological grade, inducible nitric oxide synthase, matrix metalloproteinase-2, CD-34, Caspase-3, and CD8 in invasive ductal carcinoma of the breast.}, journal = {Saudi medical journal}, volume = {31}, number = {2}, pages = {130-134}, pmid = {20174726}, issn = {1658-3175}, mesh = {Adult ; Aged ; Antigens, CD34/*immunology ; Breast Neoplasms/enzymology/immunology/*pathology ; CD8 Antigens/*immunology ; Carcinoma, Ductal/enzymology/immunology/*pathology ; Caspase 3/*metabolism ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Nitric Oxide Synthase Type II/*metabolism ; }, abstract = {OBJECTIVE: To assess by immunohistochemistry the cyclooxygenase-2 (COX-2) expression in invasive ductal carcinoma and its possible correlation with the histological grade, inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP2), and other common immunohistochemical parameters (CD-34, Caspase-3, and CD8).

METHODS: This was a retrospective pathology archive study including 50 female patients and was performed in Mustafa Kemal University, Hatay, and Sutcu Imam University, Kahraman Maras, Turkey. The routine hematoxylin-eosin staining and COX-2, iNOS, MMP-2, CD-34, CASP-3, and CD8 immunoperoxidase techniques were performed on paraffin-embedded tissues.

RESULTS: The mean value of COX-2 was 274.02+/-54.49 and MMP-2 was 263.42+/-54.30, whereas the mean iNOS values were 258.10+/-56.05. CD-34 staining also yielded positive results as 26.18+/-8.00. The mean value of CASP-3 was 284.06+/-41.2 and CD8 was 164.17+/-69.5. This reveals an inverse correlation between CASP-3 reactivity and CD8 (Spearman correlation [r]= -0.33, p=0.01). There was also an inverse correlation between iNOS reactivity and patients age (r = -0.29, p=0.03). There was a positive correlation with COX-2 and MMP-2 (p=0.00), but there was no relation with COX-2 and other parameters.

CONCLUSION: COX-2 expression is an important parameter for invasive ductal carcinoma of the breast. We found a positive correlation between COX-2 and MMP-2, whereas, we could not show direct correlation between COX-2 and iNOS, CD-34, CASP-3, and CD8.}, } @article {pmid20162457, year = {2010}, author = {Wasif, N and Maggard, MA and Ko, CY and Giuliano, AE}, title = {Invasive lobular vs. ductal breast cancer: a stage-matched comparison of outcomes.}, journal = {Annals of surgical oncology}, volume = {17}, number = {7}, pages = {1862-1869}, doi = {10.1245/s10434-010-0953-z}, pmid = {20162457}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/surgery ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; SEER Program ; Survival Rate ; }, abstract = {BACKGROUND: Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC), more difficult to detect mammographically, and usually diagnosed at a later stage. Does delayed diagnosis of ILC affect survival? We used a national registry to compare outcomes of patients with stage-matched ILC and IDC.

METHODS: Query of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry identified 263,408 women diagnosed with IDC or ILC between 1993 and 2003. Survival of patients matched by T and N stage was compared using Kaplan-Meier curves and log-rank analysis.

RESULTS: When compared with IDC, ILC was more likely to be >2 cm (43.1 vs. 32.6%; P < 0.001), lymph node positive (36.8 vs. 34.4%; P < 0.001), and ER positive (93.1 vs. 75.6%; P < 0.001). The 5-year disease-specific survival (DSS) was significantly better for patients with ILC than for those with IDC, before (90 vs. 88%; P < 0.001) and after matching for stage T1N0 (98 vs. 96%; P < 0.001), T2N0 (94 vs. 88%; P < 0.001), and T3N0 (92 vs. 83%, P < 0.001). The 5-year DSS for patients with nodal metastasis of ILC vs. IDC was 89% vs. 88% (P = NS) for stage T1N1, 81 vs. 73% (P < 0.001) for T2N1, and 72 vs. 56% (P < 0.001) for T3N1. Multivariate analysis identified a 14% survival benefit for ILC (hazard ratio 0.86, 95% confidence interval 0.80-0.92).

CONCLUSIONS: Stage-matched prognosis is better for patients with ILC than for those with IDC. Our findings support a different biology for ILC and are important for counseling and risk stratification.}, } @article {pmid20154588, year = {2010}, author = {Nguyen, CV and Falcón-Escobedo, R and Hunt, KK and Nayeemuddin, KM and Lester, TR and Harrell, RK and Bassett, RL and Gilcrease, MZ}, title = {Pleomorphic ductal carcinoma of the breast: predictors of decreased overall survival.}, journal = {The American journal of surgical pathology}, volume = {34}, number = {4}, pages = {486-493}, doi = {10.1097/PAS.0b013e3181ce97bf}, pmid = {20154588}, issn = {1532-0979}, mesh = {Adult ; Aged ; Breast Neoplasms/*mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*mortality/*pathology/surgery ; Cell Nucleus/pathology ; Female ; Giant Cells ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate ; Texas/epidemiology ; Young Adult ; }, abstract = {The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.}, } @article {pmid20151319, year = {2010}, author = {Chanplakorn, N and Chanplakorn, P and Suzuki, T and Ono, K and Chan, MS and Miki, Y and Saji, S and Ueno, T and Toi, M and Sasano, H}, title = {Increased estrogen sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type 1(17beta-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients.}, journal = {Breast cancer research and treatment}, volume = {120}, number = {3}, pages = {639-648}, doi = {10.1007/s10549-010-0785-3}, pmid = {20151319}, issn = {1573-7217}, mesh = {Aged ; Androstadienes/*pharmacology/therapeutic use ; Antineoplastic Agents, Hormonal/*pharmacology/therapeutic use ; Aromatase Inhibitors/*pharmacology/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*drug therapy/enzymology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/enzymology/surgery ; Clinical Trials, Phase II as Topic/statistics & numerical data ; Combined Modality Therapy ; Estradiol Dehydrogenases/*biosynthesis/genetics ; Estrogens/*metabolism ; Female ; Humans ; Ki-67 Antigen/analysis ; Mastectomy ; Middle Aged ; Multicenter Studies as Topic/statistics & numerical data ; Neoadjuvant Therapy ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasms, Hormone-Dependent/chemistry/*drug therapy/enzymology/surgery ; Postmenopause ; Receptors, Steroid/analysis ; Sulfatases/*biosynthesis/genetics ; }, abstract = {Aromatase inhibitors (AIs) are considered the gold standard for endocrine therapy of estrogen receptor (ER) positive postmenopausal breast cancer patients. The therapy may enhance therapeutic response and stabilize disease but resistance and disease progression inevitably occur in the patients. These are considered at least partly due to an emergence of alternative intratumoral estrogen production pathways. Therefore, in this study we evaluated effects of exemestane (EXE) upon the enzymes involved in intratumoral estrogen production including estrogen sulfatase (STS), 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), and estrogen sulfotransferase (EST) and correlated the findings with therapeutic responses including Ki67 labeling index (Ki67). 116 postmenopausal patients with invasive ductal carcinoma, stage II/IIIa, were enrolled in JFMC34-0601 clinical trials between March, 2006 and January, 2008. EXE of 25 mg/day was administered according to the protocol. Pre- and posttreatment specimens of 49 cases were available for this study. Status of STS, EST, 17beta-HSD1, ER, progesterone receptor (PgR), human epidermal growth factor receptor type 2 (Her2), and Ki67 in pre- and post-specimens were evaluated. Specimens examined before the therapy demonstrated following features; ER+ (100%), PgR+ (85.7%), and Her2+ (77.6%). After treatment, the number of Ki67, PgR, and ER positive carcinoma cells demonstrated significant decrement in clinical response (CliR) and pathological response (PaR) groups. Significant increment of 17beta-HSD1 and STS immunoreactivity was detected in all groups examined except for STS in PaR. EST showed significant increment in nonresponsive groups. Alterations of Ki67 of carcinoma cells before and after therapy were subclassified into three groups according to its degrees. Significant alterations of intratumoral enzymes, especially 17beta-HSD1 and STS, were correlated with Ki67 reduction after neoadjuvant EXE therapy. This is the first study demonstrating significant increment of STS and 17beta-HSD1 following AI neoadjuvant therapy of postmenopausal ER positive breast carcinoma patients. This increment may represent the compensatory response of breast carcinoma tissues to estrogen depletion.}, } @article {pmid20143189, year = {2011}, author = {Papantoniou, V and Sotiropoulou, E and Valsamaki, P and Tsaroucha, A and Sotiropoulou, M and Ptohis, N and Stipsanelli, A and Dimitrakakis, K and Marinopoulos, S and Tsiouris, S and Antsaklis, A}, title = {Breast density, scintimammographic (99m)Tc(V)DMSA uptake, and calcitonin gene related peptide (CGRP) expression in mixed invasive ductal associated with extensive in situ ductal carcinoma (IDC + DCIS) and pure invasive ductal carcinoma (IDC): correlation with estrogen receptor (ER) status, proliferation index Ki-67, and histological grade.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {18}, number = {4}, pages = {286-291}, doi = {10.1007/s12282-009-0192-y}, pmid = {20143189}, issn = {1880-4233}, mesh = {Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Calcitonin Gene-Related Peptide/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Proliferation ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Linear Models ; Mammography ; Middle Aged ; Neoplasm Grading ; Radiopharmaceuticals ; Receptors, Estrogen/*metabolism ; Retrospective Studies ; Technetium Tc 99m Dimercaptosuccinic Acid ; }, abstract = {BACKGROUND: We evaluated the variation of calcitonin gene related peptide (CGRP) expression in patients with mixed invasive with extensive in situ ductal carcinomas (IDC + DCIS) and pure IDC, in relation to mammographic breast density (%BD), proliferation-seeking radiotracer (99m)Tc(V) dimercaptosuccinic acid (DMSA) uptake (scintimammographic-SMM), proliferation index Ki-67, and estrogen receptor (ER) status. We also assessed CGRP expression with histological grade.

METHODS: We studied retrospectively 24 women with suspicious findings on mammography who were evaluated preoperatively with (99m)Tc(V)DMSA scintimammography. Histology revealed 12 IDC (grade II in 8, grade III in 4 patients; mean size ± SD, 2.6 ± 1.3 cm; mean age ± SD, 66.5 ± 13.1 years) and 12 IDC + DCIS (grade II in 6, grade III in 6 patients; DCIS component mean size ± SD, 5.3 ± 1.8 cm; IDC component mean size ± SD, 2.5 ± 1.1 cm; mean age ± SD, 58.5 ± 15.1 years). Immunohistochemistry for CGRP, Ki-67, and ER status was performed in all 24 surgical specimens. BD and SMM were calculated by computer-assisted methods and were statistically correlated with CGRP expression. BD, SMM, Ki-67, and ER were statistically compared between IDC and IDC + DCIS, whereas CGRP, Ki-67, and ER were compared between patients with BD >25 and <25%. CGRP was also compared (t test) between grade II and grade III in both groups.

RESULTS: Overall positive correlation was found between BD and CGRP (r = 0.577, P < 0.001). Positive correlation was established between SMM and CGRP only in IDC + DCIS (r (SMM(IDC+DCIS)-CGRP) = 0.634, P < 0.05). CGRP and Ki-67 were significantly higher in patients with BD >25% compared with <25% BD patients (P = 0.00008 and P = 0.014, respectively). BD and SMM were significantly higher in CGRP(+) than in CGRP(-) patients as well as in IDC + DCIS compared with IDC. Ki-67 was significantly higher, whereas ER was significantly lower, in IDC + DCIS than in IDC. In all patients, CGRP was significantly higher in grade II as compared with grade III (P = 0.005). In the mixed group (IDC + DCIS), grade II cancers had also significantly higher CGRP values as compared with grade III ones (P = 0.004). In pure IDC, no statistical difference was found between grade II and III (P = 0.4).

CONCLUSIONS: ΒD, SMM, CGRP, and Ki-67 were significantly increased, whereas ER was significantly decreased, in IDC + DCIS as compared with IDC, indicating that IDC + DCIS is an entity that is more aggressive, ER independent, and possibly associated with a pathway linked to stromal involvement and CGRP activity.}, } @article {pmid20143153, year = {2010}, author = {Jung, SY and Kim, HY and Nam, BH and Min, SY and Lee, SJ and Park, C and Kwon, Y and Kim, EA and Ko, KL and Shin, KH and Lee, KS and Park, IH and Lee, S and Kim, SW and Kang, HS and Ro, J}, title = {Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer.}, journal = {Breast cancer research and treatment}, volume = {120}, number = {3}, pages = {627-637}, doi = {10.1007/s10549-010-0780-8}, pmid = {20143153}, issn = {1573-7217}, mesh = {Adult ; Breast Neoplasms/chemistry/classification/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/classification/mortality/*pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Metaplasia ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Republic of Korea/epidemiology ; Retrospective Studies ; Treatment Outcome ; }, abstract = {The present study was designed to assess the clinical characteristics and outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. Mean age of patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P < 0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04), higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/- 26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P < 0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC patients experienced disease recurrence with a median follow-up of 47.2 months (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence and overall survival in univariate and multivariate analysis (HR 3.89 in recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI: 1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive pathological features. Patients with MBC appeared to have inherently aggressive tumor biology with poorer clinical outcomes than those with general IDC or TN-IDC.}, } @article {pmid20143146, year = {2010}, author = {Guttmann-Steinmetz, S and Gadow, KD and DeVincent, CJ and Crowell, J}, title = {Anxiety symptoms in boys with autism spectrum disorder, attention-deficit hyperactivity disorder, or chronic multiple tic disorder and community controls.}, journal = {Journal of autism and developmental disorders}, volume = {40}, number = {8}, pages = {1006-1016}, pmid = {20143146}, issn = {1573-3432}, support = {MH 45358/MH/NIMH NIH HHS/United States ; }, mesh = {Analysis of Variance ; Anxiety Disorders/*complications/psychology ; Attention Deficit Disorder with Hyperactivity/*complications/psychology ; Case-Control Studies ; Child ; Child Development Disorders, Pervasive/*complications/psychology ; Humans ; Male ; Psychiatric Status Rating Scales ; Tic Disorders/*complications/psychology ; Wechsler Scales ; }, abstract = {We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with neurobehavioral syndromes: attention-deficit/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were assessed using parent and teacher versions of a DSM-IV-referenced rating scale. All three groups of boys with co-morbid ADHD evidenced more severe anxiety than Controls. Group differences in anxiety varied as a function of symptom, disorder, informant, and co-morbidity supporting the notion that co-morbid neurobehavioral syndromes differentially impact clinical features of co-occurring anxiety symptoms. Findings also suggest that GAD and SAD are phenomenologically unique, even in children with ASD. Implications for nosology are discussed.}, } @article {pmid20137353, year = {2009}, author = {Yin, HF and Wang, YH and Qin, XQ and Zhang, H and Li, T and Ye, JM and Liu, YH}, title = {[Effect of neoadjuvant chemotherapy on histologic grade and expression of biological markers in breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {31}, number = {11}, pages = {858-862}, pmid = {20137353}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; *Breast Neoplasms/drug therapy/metabolism/pathology ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Carcinoma, Lobular/drug therapy/metabolism/pathology ; Docetaxel ; Epirubicin/administration & dosage ; Female ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoadjuvant Therapy/*methods ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Taxoids/administration & dosage ; }, abstract = {OBJECTIVE: The aim of this study is to investigate the changes of expression of estrogen receptors (ER), progesterone receptors (PR), Her-2, Ki-67 and histological grade after neoadjuvant chemotherapy in breast cancer.

METHODS: Sixty-seven patients with histopathalogically confirmed breast cancer by core needle biopsy received neoadjuvant chemotherapy. The effect of neoadjuvant chemotherapy was assessed according to the criteria of the Japanese Breast Cancer Society: non-effective (G1), mildly effective (G2), moderately effective (G3), markedly effective (G4) and completely effective (G5). All pathological slides were retrospectively reviewed. Immunohistochemical staining (EnVision method) was used to detect the expression of ER and PR, Her-2 and Ki-67. The pre- and post-neoadjuvant chemotherapy status of tumor histological grade, ER and PR, Her-2 and Ki-67 expression in the 49 cases were compared.

RESULTS: The effect of neoadjuvant chemotherapy was assessed in 67 patients. There were 5 cases (7.5%) in G1, 19 in G2 (28.4%), 20 in G3 (29.9%), 17 in G4 (25.4%) and 6 in G5 (9.0%), respectively. PR positive rate was 71.4% after chemotherapy versus 91.8% before chemotherapy, with a statistically significant reduction (P = 0.021). However, the ER and Her-2 expression before and after neoadjuvant chemotherapy was stable. Of the patients with invasive ductal carcinoma, 28.6% had histological grade change after neoadjuvant chemotherapy, and 85.7% of patients decreased one grade. The proportion of histological grade change in the G1, G2, G3, G4 were 0, 5.9%, 41.2% and 54.5%, respectively (P = 0.013). The average rate of Ki-67 expression decreased from 28.3% pre-chemotherapy to 11.0% post-chemotherapy (P = 0.011). After the neoadjuvant chemotherapy, the Ki-67 expression rate decreased by > 10%, > 20%, > 30%, > 40% and > 50% in 3 groups (G1 and G2, group G3, group G4 and G5) showed a tendency to be increased, with a significant difference (P < 0.05).

CONCLUSION: PR expression in breast cancer decreases after neoadjuvant chemotherapy, while ER and Her-2 expressions remain stable. After neoadjuvant chemotherapy, the histological grade and proliferation index are decreased and correlated with the response to chemotherapy. Therefore, histological grade and proliferation index may be effective complementary factors in assessment of the effectiveness of neoadjuvant chemotherapy.}, } @article {pmid20137352, year = {2009}, author = {Ding, JH and Peng, WJ and Jiang, ZX and Xu, LH and Hu, DT and Zheng, XJ}, title = {[Diagnostic value of full-field digital mammography for breast carcinoma].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {31}, number = {11}, pages = {854-857}, pmid = {20137352}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Diseases/diagnosis/diagnostic imaging ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Calcinosis/diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Diagnostic Errors ; Female ; Fibrocystic Breast Disease/*diagnosis/diagnostic imaging ; Humans ; Mammography/*methods ; Middle Aged ; Radiographic Image Interpretation, Computer-Assisted ; Retrospective Studies ; }, abstract = {OBJECTIVE: To evaluate the diagnostic value of full-field digital mammography for breast cancer.

METHODS: The clinical data and mammograms of 230 patients with breast diseases between January 2008 and July 2008 were collected and reviewed. Craniocaudal (CC) and mediolateral oblique (MLO) view mammograms were performed in all patients before surgery. Three experienced radiologists in breast imaging assessment analyzed and classified all the mammograms according to breast imaging reporting and data system (BI-RADS). The sensitivity, specificity and accuracy were evaluated according to their pathological diagnosis. The reasons resulting in false-negative and false-positive diagnosis were also analyzed.

RESULTS: Of the 238 samples, 130 had a malignant breast tumors and 108 cases of benign breast lesions. One hundred and nine of the 130 malignant breast tumors were invasive ductal carcinoma. Fifty-seven of the 108 benign breast lesions were breast adenosis. Masses or masses with microcalcification were the most frequently seen signs of the malignant tumors, accounting for 40.8% and 20.8%, respectively. The sensitivity, specificity and accuracy of FFDM in detecting breast carcinoma were 90.8%, 87.0% and 89.1%, respectively. The false-negative signs including negative X-ray finding (5 cases) and focal asymmetric densities (4 cases). The false-positive signs were masses with spiculate, indistinctive or lobulated margin leading to misdiagnosing the lesions as malignant tumors.

CONCLUSION: Full-field digital mammography (FFDM) is helpful in detection of breast cancers in women, with a higher sensitivity, specificity and accuracy, and has an important clinical application value.}, } @article {pmid20134315, year = {2010}, author = {Takahashi, H and Ohigashi, H and Ishikawa, O and Eguchi, H and Gotoh, K and Yamada, T and Nakaizumi, A and Uehara, H and Tomita, Y and Nishiyama, K and Yano, M}, title = {Serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation therapy for resectable invasive ductal carcinoma of the pancreas as an indicator for therapeutic selection and survival.}, journal = {Annals of surgery}, volume = {251}, number = {3}, pages = {461-469}, doi = {10.1097/SLA.0b013e3181cc90a3}, pmid = {20134315}, issn = {1528-1140}, mesh = {Aged ; Algorithms ; Antimetabolites, Antineoplastic/*therapeutic use ; CA-19-9 Antigen/*blood ; Carcinoma, Pancreatic Ductal/*blood/*drug therapy/mortality/radiotherapy ; Combined Modality Therapy ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*blood/*drug therapy/mortality/radiotherapy ; Preoperative Care ; Retrospective Studies ; Survival Rate ; Gemcitabine ; }, abstract = {OBJECTIVE: To evaluate serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation therapy (CRT) for resectable pancreatic cancer (PC) in the earlier identification of patients who are likely to benefit from subsequent resection.

SUMMARY BACKGROUND DATA: One of the advantages of the preoperative CRT strategy for patients with advanced PC is that undetectable systemic disease may be revealed during preoperative CRT, thus avoiding unnecessary surgery. Serum CA19-9 has been evaluated as a predictive indicator of the treatment efficacy and outcome in various clinical settings.

METHODS: We retrospectively reviewed 64 consecutive patients with resectable PC (at diagnosis) who received preoperative CRT at our hospital between 2002 and 2008. Patients were divided into 2 groups (efficacy grouping) to evaluate the efficacy of preoperative CRT according to the clinical course. Group A included patients who were unable to receive the subsequent resection due to the development of unresectable factors during preoperative CRT and those who received the subsequent resection but developed recurrent disease within 6 months after surgery; group B included patients who received the subsequent resection and survived without recurrences for more than 6 months after surgery. We developed a new classification utilizing pretreatment CA19-9 and proportional alteration of CA19-9 2 months after the initiation of treatment. The categories were defined as: I (increased), MD (modestly decreased), and SD (substantially decreased). Clinicopathological variables and CA19-9 alteration status were correlated with the efficacy grouping and overall survival.

RESULTS: All of the category I patients were included in group A, 93.5% of the category SD patients in group B, and approximately half of the category MD patients in group A. CA19-9 alteration status was a single independent variable associated with efficacy grouping and overall patient survival, with the 1-year survival rate of category I patients, and the 4-year survival rate of category MD and SD patients being 22.2%, 34.1%, and 58.9%, respectively.

CONCLUSIONS: CA19-9 alteration status is useful in identifying those who will benefit from the preoperative CRT and subsequent resection and those who will not; it was a significant predictor for patient prognosis in the setting of the preoperative CRT strategy for resectable PC.}, } @article {pmid20110783, year = {2010}, author = {Puente, J and Manzano, A and Martin, M and López-Tarruella, S and Díaz-Rubio, E}, title = {Breast cancer: complete response with the combination of sunitinib and trastuzumab in a patient with grade III ductal carcinoma.}, journal = {Anti-cancer drugs}, volume = {21 Suppl 1}, number = {}, pages = {S19-22}, doi = {10.1097/01.cad.0000361532.36428.42}, pmid = {20110783}, issn = {1473-5741}, mesh = {Antibodies, Monoclonal/*administration & dosage/adverse effects ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*administration & dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/*drug therapy/pathology/radiotherapy ; Carcinoma, Ductal, Breast/*drug therapy/pathology/radiotherapy ; Diarrhea/chemically induced ; Female ; Heart Function Tests/drug effects ; Humans ; Hypothyroidism/chemically induced ; Indoles/*administration & dosage/adverse effects ; Lymphatic Metastasis ; Middle Aged ; Paclitaxel/administration & dosage/adverse effects ; Pyrroles/*administration & dosage/adverse effects ; Remission Induction ; Sunitinib ; Trastuzumab ; }, abstract = {In August 2000, a previously healthy postmenopausal 52-year-old woman was diagnosed with grade III invasive ductal carcinoma. The tumor had an ER -, PR -, and HER2 + profile. Adjuvant treatment with FEC was initiated followed by radiotherapy. In October 2004, the patient presented a clinically asymptomatic supraclavicular and mediastinal lymph node recurrence and treatment with paclitaxel and trastuzumab was initiated. A complete response was achieved after 20 weeks of treatment, and in January 2006 treatment was interrupted due to toxicity. After a 34-month free-of-relapse period, a local recurrence was detected in the chest wall. In September 2007, the patient joined a phase II trial with sunitinib (37.5 mg once a day in 28 days cycles) and trastuzumab (6 mg/kg every 3 weeks), after having verified a normal cardiac function. After two courses, a partial cutaneous response and a complete radiological response were obtained. The most relevant toxicities included cutaneous hyperpigmentation, dysgeusia, mucositis, grade II diarrhea and hypertension. The development of grade III diarrhea led to sunitinib dose reduction (25mg/day). In January 2008, the patient developed hypothyroidism and a significant drop in the left ventricular ejection fraction that led to treatment interruption. In March 2008, once cardiac function was recovered, treatment at the same dose was reinitiated. After two months of treatment, a new descent in cardiac function was noted which led to the suspension of sunitinib, and the interruption of the trastuzumab treatment until recovery of normal cardiac function. In July 2008, trastuzumab monotherapy was resumed and since then no cardiac events have been reported, while maintaining a radiological and clinical response.}, } @article {pmid20123903, year = {2010}, author = {Bhooshan, N and Giger, ML and Jansen, SA and Li, H and Lan, L and Newstead, GM}, title = {Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers.}, journal = {Radiology}, volume = {254}, number = {3}, pages = {680-690}, pmid = {20123903}, issn = {1527-1315}, support = {P50 CA125183/CA/NCI NIH HHS/United States ; R33 CA113800/CA/NCI NIH HHS/United States ; R33-113800//PHS HHS/United States ; P50-CA125183/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Bayes Theorem ; Breast Neoplasms/*diagnosis/pathology ; Contrast Media ; Diagnosis, Computer-Assisted/*methods ; Diagnosis, Differential ; Discriminant Analysis ; Female ; Fuzzy Logic ; Humans ; Image Enhancement/*methods ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Prognosis ; ROC Curve ; Retrospective Studies ; }, abstract = {PURPOSE: To assess the performance of computer-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging kinetic and morphologic features in the differentiation of invasive versus noninvasive breast lesions and metastatic versus nonmetastatic breast lesions.

MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, in which the requirement for informed patient consent was waived, breast MR images were retrospectively collected. The images had been obtained with a 1.5-T MR unit by using a gadodiamide-enhanced T1-weighted spoiled gradient-recalled acquisition in the steady state sequence. The breast MR imaging database contained 132 benign, 71 ductal carcinoma in situ (DCIS), and 150 invasive ductal carcinoma (IDC) lesions. Fifty-four IDC lesions were associated with metastasis-positive lymph nodes (LNs), and 64 IDC lesions were associated with negative LNs. Lesion segmentation and extraction of morphologic and kinetic features were automatically performed by a laboratory-developed computer workstation. Features were first selected by using stepwise linear discriminant analysis and then merged by using Bayesian neural networks. Lesion classification performance was assessed with receiver operating characteristic analysis.

RESULTS: Differentiation of DCIS from IDC lesions yielded an area under the receiver operating characteristic curve (AUC) of 0.83 +/- 0.03 (standard error). AUCs were 0.85 +/- 0.02 for differentiation between IDC and benign lesions and 0.79 +/- 0.03 for differentiation between DCIS and benign lesions. Differentiation between IDC lesions associated with positive LNs and IDC lesions associated with negative LNs yielded an AUC of 0.82 +/- 0.04. AUCs were 0.86 +/- 0.03 for differentiation between IDC lesions associated with positive LNs and benign lesions and 0.83 +/- 0.03 for differentiation between IDC lesions associated with negative LNs and benign lesions.

CONCLUSION: Computer-aided diagnosis of breast DCE MR imaging-depicted lesions was extended from the task of discriminating between malignant and benign lesions to the prognostic tasks of distinguishing between noninvasive and invasive lesions and discriminating between metastatic and nonmetastatic lesions, yielding MR imaging-based prognostic markers.

SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090838/-/DC1.}, } @article {pmid20118911, year = {2010}, author = {Hasebe, T and Tamura, N and Iwasaki, M and Okada, N and Akashi-Tanaka, S and Hojo, T and Shimizu, C and Adachi, M and Fujiwara, Y and Shibata, T and Sasajima, Y and Tsuda, H and Kinoshita, T}, title = {Grading system for lymph vessel tumor emboli: significant outcome predictor for patients with invasive ductal carcinoma of the breast who received neoadjuvant therapy.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {4}, pages = {581-592}, doi = {10.1038/modpathol.2010.3}, pmid = {20118911}, issn = {1530-0285}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoadjuvant Therapy ; Neoplastic Cells, Circulating/*pathology ; Prognosis ; Proportional Hazards Models ; }, abstract = {The purpose of this study was to confirm that the grades of lymph vessel tumor emboli in biopsy specimens obtained before neoadjuvant therapy and in the surgical specimens obtained after neoadjuvant therapy according to the grading system we devised are significant histological outcome predictor for invasive ductal carcinoma (IDC) patients who received neoadjuvant therapy. The subjects of this study were the 318 consecutive IDC patients who had received neoadjuvant therapy in our institution. The lymph vessel tumor embolus grades in the biopsy specimens and in the surgical specimens were significantly associated with the increases in mean number of nodal metastases. Multivariate analyses with well-known prognostic factors and p53 expression in tumor-stromal fibroblasts clearly showed that the lymph vessel tumor embolus grade based on the biopsy specimens and based on the surgical specimens significantly increased the hazard rates for tumor recurrence and tumor-related death in all the IDC patients as a whole, in the IDC patients who did not have nodal metastasis, and in the IDC patients who had nodal metastasis, and the outcome-predictive power of the lymph vessel tumor embolus grades based on the surgical specimens was superior to that of the lymph vessel tumor embolus grades based on the biopsy specimens. The grades in the grading system for lymph vessel tumor emboli were significantly associated with nodal metastasis, and the histological grading system is an excellent system for accurately predicting the outcome of patients with IDC of the breast who have received neoadjuvant therapy.}, } @article {pmid20108215, year = {2009}, author = {Peres, RM and Serra, KP and Derchain, SF and Yoon, JH and Pinto, GA and Alvarenga, M and Soares, FA and Heinrich, JK and da Cunha, IW and Vassallo, J and Sarian, LO}, title = {Comparative evaluation of the erbB2 and hormone receptor status of neighboring invasive and in situ components of ductal carcinomas of the breast.}, journal = {The International journal of biological markers}, volume = {24}, number = {4}, pages = {238-244}, doi = {10.1177/172460080902400404}, pmid = {20108215}, issn = {0393-6155}, mesh = {Adult ; Aged ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; }, abstract = {BACKGROUND: It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast.

OBJECTIVES: To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC).

SUBJECTS AND METHODS: Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH - only erbB2).

RESULTS: The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components.

CONCLUSION: Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.}, } @article {pmid20107518, year = {2010}, author = {Chaal, BK and Gupta, AP and Wastuwidyaningtyas, BD and Luah, YH and Bozdech, Z}, title = {Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.}, journal = {PLoS pathogens}, volume = {6}, number = {1}, pages = {e1000737}, pmid = {20107518}, issn = {1553-7374}, mesh = {Enzyme Inhibitors/pharmacology ; Gene Expression Regulation, Developmental/*physiology ; Histone Deacetylases/*genetics ; Immunoprecipitation ; Oligonucleotide Array Sequence Analysis ; Peptides, Cyclic/pharmacology ; Plasmodium falciparum/*growth & development/*physiology ; RNA, Messenger/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; *Transcription, Genetic ; }, abstract = {The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.}, } @article {pmid20105336, year = {2010}, author = {Liu, XJ and Shen, P and Wang, XF and Sun, K and Sun, FF}, title = {Solitary adrenal metastasis from invasive ductal breast cancer: an uncommon finding.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {7}, pmid = {20105336}, issn = {1477-7819}, mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; *Mastectomy, Modified Radical ; Middle Aged ; Prognosis ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) of the breast usually metastasizes to the lungs, liver, bones and brain. Solitary adrenal metastasis is extremely rare. Due to the rarity of this condition, the optimal treatment is unclear. We report the first case of IDC of the breast metastasizing solely to the adrenal gland after a modified radical mastectomy but having a long-term disease-free survival while treated merely by a left adrenalectomy.

CASE PRESENTATION: A 64-year-old woman was found a left adrenal mass on a follow-up visit two years after taking a right modified radical mastectomy for the breast cancer. She was subsequently given a left adrenalectomy. Postoperative histopathology findings were compatible with invasive ductal carcinoma (IDC) of the breast. Due to the patient's refusal, no further treatments were offered after the adrenalectomy. The patient now is still alive and has no sign of relapse. Survival time after taking the right modified radical mastectomy and the left adrenalectomy is more than five years and three years, respectively.

CONCLUSION: This is the first case of a patient with solitary, metachronous adrenal metastasis from IDC of the breast to be reported. For patients in this condition, complete removal of metastasized organ may translate into survival benefit.}, } @article {pmid20105298, year = {2010}, author = {Tada, K and Ogiya, A and Kimura, K and Morizono, H and Iijima, K and Miyagi, Y and Nishimura, S and Makita, M and Horii, R and Akiyama, F and Iwase, T}, title = {Ductal carcinoma in situ and sentinel lymph node metastasis in breast cancer.}, journal = {World journal of surgical oncology}, volume = {8}, number = {}, pages = {6}, pmid = {20105298}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Intraductal, Noninfiltrating/*secondary ; Female ; Humans ; Incidence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate.

METHODS: We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size.

RESULTS: Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001).

CONCLUSIONS: Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.}, } @article {pmid20103682, year = {2010}, author = {Park, SY and Lee, HE and Li, H and Shipitsin, M and Gelman, R and Polyak, K}, title = {Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {16}, number = {3}, pages = {876-887}, pmid = {20103682}, issn = {1557-3265}, support = {P50 CA089393-100014/CA/NCI NIH HHS/United States ; P50 CA089393-090014/CA/NCI NIH HHS/United States ; P50 CA089393/CA/NCI NIH HHS/United States ; CA006516/CA/NCI NIH HHS/United States ; CA89393/CA/NCI NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase/metabolism ; Aldehyde Dehydrogenase 1 Family ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*pathology ; CD24 Antigen/metabolism ; Carcinoma, Ductal/*metabolism/*pathology ; Disease Progression ; Female ; Humans ; Hyaluronan Receptors/metabolism ; Isoenzymes/metabolism ; Neoplastic Stem Cells/*metabolism ; Retinal Dehydrogenase ; }, abstract = {PURPOSE: To evaluate the expression of stem cell-related markers at the cellular level in human breast tumors of different subtypes and histologic stage.

EXPERIMENTAL DESIGN: We performed immunohistochemical analyses of 12 proteins [CD44, CD24, ALDH1, vimentin, osteonectin, EPCR, caveolin 1, connexin 43, cytokeratin 18 (CK18), MUC1, claudin 7, and GATA3] selected based on their differential expression in breast cancer cells with more differentiated and stem cell-like characteristics in 47 cases of invasive ductal carcinoma (IDC) only, 135 cases of IDC with ductal carcinoma in situ (DCIS), 35 cases of DCIS with microinvasion, and 58 cases of pure DCIS. We also analyzed 73 IDCs with adjacent DCIS to determine the differences in the expression of markers by histology within individual tumors. CD44+/CD24- and CD24-/CD24+ cells were detected using double immunohistochemistry.

RESULTS: CD44 and EPCR expression was different among the four histologic groups and was lower in invasive compared with in situ tumors, especially in luminal A subtype. The expression of vimentin, osteonectin, connexin 43, ALDH1, CK18, GATA3, and MUC1 differed by tumor subtype in some histologic groups. ALDH1-positive cells were more frequent in basal-like and HER2+ than in luminal tumors. CD44+/CD24- cells were detected in 69% of all tumors with 100% of the basal-like and 52% of HER2+ tumors having some of these cells.

CONCLUSIONS: Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage.}, } @article {pmid20102902, year = {2010}, author = {Plehn, G and Vormbrock, J and Perings, S and Plehn, A and Meissner, A and Butz, T and Trappe, HJ}, title = {Comparison of right ventricular functional response to exercise in hypertrophic versus idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {105}, number = {1}, pages = {116-121}, doi = {10.1016/j.amjcard.2009.08.662}, pmid = {20102902}, issn = {1879-1913}, mesh = {Cardiac Catheterization ; Cardiomyopathy, Dilated/diagnosis/*physiopathology ; Cardiomyopathy, Hypertrophic/diagnosis/*physiopathology ; Echocardiography, Doppler ; Exercise Test ; Exercise Tolerance/*physiology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Ventricular Function, Right/*physiology ; }, abstract = {Although the biventricular nature of the disease has been confirmed by morphologic studies, information on right ventricular (RV) function in hypertrophic cardiomyopathy (HC) is lacking. The aim of the study was to hemodynamically characterize RV performance in HC versus idiopathic dilated cardiomyopathy (IDC) during exercise. The hemodynamic data of 63 patients with HC who underwent hemodynamic exercise testing with thermodilution-derived assessment of RV ejection fraction were analyzed. The results were compared to a healthy control group (n = 20) and to patients with IDC (n = 86). The baseline RV ejection fraction was increased in the patients with HC compared to those with IDC (39 +/- 10% vs 33 +/- 12%; p = 0.002), but did not differ compared to controls (42 +/- 7% vs 39 +/- 10%; p = NS). An increase in end-diastolic volume from rest to exercise contributed to stroke volume augmentation in those with HC (121 +/- 38 vs 136 +/- 55 ml/m(2); p = 0.01) and control subjects (116 +/- 34 vs 138 +/- 31 ml/m(2); p = 0.002) but not in those with IDC (117 +/- 47 vs 120 +/- 52 ml/m(2); p = NS). At peak exercise the RV ejection fraction in those with HC was reduced compared to that in the controls (45 +/- 11% vs 59% +/- 9%; p <0.001), but it was increased compared to that in those with IDC (45 +/- 11% vs 35% +/- 11%; p <0.001). In conclusion, the extent of the pulmonary pressure increase was more pronounced in those with HC than in those with IDC, but the degree of functional impairment of the right ventricle was less severe, probably owing to its ability to recruit preload and contractile reserve with exercise.}, } @article {pmid20091034, year = {2012}, author = {Azar, L and Fischer, HD}, title = {Perivascular carotid inflammation: an unusual case of carotidynia.}, journal = {Rheumatology international}, volume = {32}, number = {2}, pages = {457-459}, pmid = {20091034}, issn = {1437-160X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carotid Artery Diseases/*chemically induced/diagnostic imaging/pathology ; Carotid Artery, Common/diagnostic imaging/*drug effects/pathology ; Diagnosis, Differential ; Female ; Humans ; Inflammation/chemically induced/diagnosis/pathology ; Middle Aged ; Neck Pain/*etiology/pathology ; Radiography ; Vasculitis/chemically induced/diagnostic imaging/pathology ; }, abstract = {A 59-year-old woman was admitted to the hospital with a fever and rigors for 2 days. She was on chemotherapy (docetaxel, carboplatin, and trastuzumab) for her stage II invasive ductal carcinoma of the breast. Her physical exam was unremarkable except for the fever. The white blood cells were 21,200/mm(3) with 92% of neutrophils. ESR was 106 mm/h. An extensive infectious workup was negative. On day 6, while still febrile, the patient complained of a left-sided neck pain. She exhibited tenderness over the left carotid artery. A CT scan of the neck without intravenous contrast showed perivascular inflammation of the left common carotid artery, without evidence of a collection, arterial thrombosis, aneurysm, or dissection. The etiology of this finding was possibly chemotherapy related. It dramatically responded to oral prednisone. A repeat CT scan of the neck with IV contrast 2 weeks later showed a remarkable improvement. Drug reactions can simulate systemic inflammatory diseases and should always be considered in the diagnosing process.}, } @article {pmid20087450, year = {2009}, author = {Tio, RA and Slart, RH and de Boer, RA and van der Vleuten, PA and de Jong, RM and van Wijk, LM and Willems, T and Lubbers, DD and Voors, AA and van Veldhuisen, DJ}, title = {Reduced regional myocardial perfusion reserve is associated with impaired contractile performance in idiopathic dilated cardiomyopathy.}, journal = {Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation}, volume = {17}, number = {12}, pages = {470-474}, pmid = {20087450}, issn = {1876-6250}, abstract = {Background. In idiopathic dilated cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. Subclinical myocardial ischaemia may contribute to progressive deterioration of left ventricular function. The relation between regional myocardial perfusion reserve (MPR) and contractile performance was investigated.Methods. Patients with newly diagnosed IDC underwent positron emission tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dypiridamole stress), and (18)F-fluorodeoxyglucose viability tracer and a dobutamine stress MRI. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17-segment model.Results. Twenty-two patients were included (age 49+/-11 years; 15 males, LVEF 33+/-10%). With MRI, a total of 305 segments could be analysed. Wall motion abnormalities at rest were present in 127 (35.5%) segments and in 103 (29.9%) during dobutamine stress. Twenty-one segments deteriorated during stress and 43 improved. MPR was significantly higher in those segments that improved, compared with those that did not change or were impaired during stress (1.87+/-0.04 vs. 1.56+/- 0.07 p<0.01.)Conclusion. Signs of regional ischaemia were clearly present in IDC patients. Ischaemic regions displayed impaired contractility during stress. This suggests that impaired oxygen supply contributes to cardiac dysfunction in IDC. (Neth Heart J 2009;17:470-4.).}, } @article {pmid20087043, year = {2010}, author = {Konishi, K and Hasegawa, N and Kaneko, H and Iimura, Y and Shoji, Y and Kawabata, M}, title = {[Two cases of breast cancer responding to primary systemic chemotherapy containing trastuzumab without surgery].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {1}, pages = {115-118}, pmid = {20087043}, issn = {0385-0684}, mesh = {Adult ; Antibodies, Monoclonal/*administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Carcinoma, Lobular/*drug therapy ; Combined Modality Therapy ; Female ; Humans ; Trastuzumab ; }, abstract = {The first case was a 40-year-old woman who was referred to our hospital with a complaint of left breast tumor. She was diagnosed as invasive ductal carcinoma (T2N0M0, Stage IIA). The tumor was ER-negative, PR-negative and HER2-positive. After primary systemic chemotherapy with 6 courses of 5-fluorouracil+epirubicin+cyclophosphamide(FEC)and 3 courses of weekly paclitaxel (PTX)+trastuzumab, the efficacy of chemotherapy was judged as a complete response (CR). After chemotherapy, radiotherapy for her left breast was performed without surgery. At 21 months after CR, local efficacy was judged as CR, but liver and bone metastases appeared, and were treated by capecitabine and trastuzumab. The efficacy of chemotherapy was judged as a partial response (PR). The second case was a 26-year-old woman referred to our hospital with a complaint of right breast tumor. She was diagnosed as invasive lobular carcinoma (T2N0M0, Stage IIA). The tumor was ER-positive, PR-negative and HER2-positive. After primary systemic chemotherapy with 4 courses of FEC and 6 courses of docetaxel+trastuzumab, the efficacy of chemotherapy was judged as CR. Then, 4 courses of weekly PTX+trastuzumab were performed. After chemotherapy, radiotherapy for her right breast was performed without surgery. The efficacy of treatment was judged as CR for 15 months.}, } @article {pmid20087042, year = {2010}, author = {Konishi, K and Hasegawa, N and Kaneko, H and Iimura, Y and Shoji, Y and Kawabata, M}, title = {[A case of premenopausal stage IV breast cancer responding to neoadjuvant endocrine therapy after chemotherapy with FEC].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {37}, number = {1}, pages = {111-113}, pmid = {20087042}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Agents, Hormonal/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Cyclophosphamide/therapeutic use ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Goserelin/*administration & dosage ; Humans ; Mastectomy ; Neoadjuvant Therapy ; Premenopause ; Tamoxifen/*administration & dosage ; }, abstract = {A 33-year-old woman was referred to our hospital with a complaint of left breast tumor. After examinations, she was diagnosed as invasive ductal carcinoma with sternum metastasis (T2N0M1(OSS), Stage IV). The tumor was hormone receptor- positive and HER2-negative. Primary systemic chemotherapy with FEC was performed. After four courses, the efficacy was judged as a partial response (PR). After chemotherapy, endocrine therapy with goserelin and tamoxifen was performed. The efficacy of endocrine therapy was as good as that of chemotherapy. After endocrine therapy for 13 months, breast conserving-surgery was performed. After surgery, radiotherapy for left breast and sternum was performed. She continues to undergo outpatient endocrine therapy with no detectable tumor. It is suggested that neoadjuvant endocrine therapy may be useful with consideration for treatment effectiveness and the patient's quality of life.}, } @article {pmid20082408, year = {2010}, author = {Kelten, C and Sen Turk, N and Kesen, Z and Akbulut, M and Duzcan, E}, title = {Fine-needle aspiration biopsy of an invasive ductal carcinoma with medullary features presented with abscess formation.}, journal = {Diagnostic cytopathology}, volume = {38}, number = {8}, pages = {624-625}, doi = {10.1002/dc.21266}, pmid = {20082408}, issn = {1097-0339}, mesh = {Abscess/*complications ; Adult ; Biopsy, Fine-Needle ; Breast/*pathology ; Breast Neoplasms/*complications/*pathology ; Carcinoma, Ductal, Breast/*complications/*pathology ; Carcinoma, Medullary/*pathology ; Female ; Humans ; }, } @article {pmid20081807, year = {2010}, author = {van der Vegt, B and Wesseling, J and Pijnappel, RM and Dorrius, MD and den Heeten, GJ and de Roos, MA and de Bock, GH}, title = {Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {23}, number = {4}, pages = {629-636}, doi = {10.1038/modpathol.2009.188}, pmid = {20081807}, issn = {1530-0285}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/metabolism/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Mammography ; Mass Screening/methods ; Middle Aged ; Postmenopause ; Proportional Hazards Models ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Estrogen/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; Retrospective Studies ; Tissue Array Analysis ; Tumor Suppressor Protein p53/biosynthesis/genetics ; }, abstract = {There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between 'true' interval carcinomas and screen-detected/missed carcinomas hypothesising that 'true' interval carcinomas show a more aggressive biological behaviour. The study group consisted of 92 consecutive postmenopausal women attending the breast screening programme and presenting with an invasive ductal carcinoma. All screening mammograms were re-reviewed. Sixteen patients had a 'true' interval carcinoma. Seven carcinomas were missed at screening, but detected on re-reviewing of the screening mammogram. Radiological characteristics were assessed from diagnostic mammograms. Data on patient- and tumour characteristics and follow-up data were recorded from hospital records. Median follow-up was 61 months. Immunohistochemistry for ER, PR, Her2/neu and p53 was performed on TMA sections. Univariate and multivariate logistic regression analyses were performed. In univariate analysis, 'true' interval carcinomas were significantly larger (odd ratios (OR) 7.2, 95% CI 1.8-28.1) and less frequently ER (OR 0.3, 95% CI 0.1-0.9) and PR (OR 0.3, 95% CI 0.1-1.0) positive. In multivariate analysis, 'true' interval carcinoma was independently associated with larger tumours (OR 7.0, 95% CI 1.4-36.2). A trend toward ER negativity was found (OR 0.3, 95% CI 0.1-1.1). 'True' interval carcinomas showed a trend toward a decreased relapse-free survival (HR 1.7 95% CI 0.9-3.1). Although 'true' interval carcinomas were significantly larger than screen-detected/missed interval carcinomas, it remains challenging to observe parameters that determine this difference between 'true' interval carcinomas and screen-detected lesions.}, } @article {pmid20079190, year = {2009}, author = {Yang, GZ and Li, J and Ding, HY}, title = {[Nipple adenoma: report of 18 cases with review of literatures].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {9}, pages = {614-616}, pmid = {20079190}, issn = {0529-5807}, mesh = {Adenoma/metabolism/*pathology/surgery ; Adult ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Adenosquamous/metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Diagnosis, Differential ; Female ; Humans ; Keratin-5/metabolism ; Keratins/metabolism ; Middle Aged ; Nipples/metabolism/*pathology/surgery ; }, abstract = {OBJECTIVE: To investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast.

METHODS: Morphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures.

RESULTS: The neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts.

CONCLUSIONS: Nipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.}, } @article {pmid20078969, year = {2009}, author = {Yin, HF and Li, T and Zhang, H and Zhang, S}, title = {[Differential diagnosis of invasive ductal carcinoma versus invasive lobular carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {10}, pages = {663-667}, pmid = {20078969}, issn = {0529-5807}, mesh = {Adaptor Proteins, Signal Transducing/metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Carcinoma, Lobular/metabolism/*pathology/surgery ; Catenins/*metabolism ; Diagnosis, Differential ; Disease-Free Survival ; Dishevelled Proteins ; Female ; Humans ; Mastectomy/methods ; Middle Aged ; Neoplasm Proteins/metabolism ; Phosphoproteins/metabolism ; Receptors, Cell Surface/metabolism ; Survival Rate ; Delta Catenin ; }, abstract = {OBJECTIVE: To study the diagnostic usefulness of immunohistochemical markers in distinguishing between invasive ductal carcinoma and invasive lobular carcinoma of breast.

METHODS: Twenty-four cases of grade I invasive ductal carcinoma, 12 cases of classic invasive lobular carcinoma and 14 cases of invasive carcinoma with mixed ductal and lobular features were retrieved from the archival files of Peking University First Hospital during the period from January, 1998 to December, 2001. Immunohistochemical study for E-cadherin, p120 catenin, epithelia membrane protein 1 (EMP1) and DVL1 was performed.

RESULTS: The positivity rates for E-cadherin in grade I invasive ductal carcinoma and classic invasive lobular carcinoma were 83.3% (20/24) and 0, respectively (P < 0.01). The positivity rates for p120 catenin were 100% in both grade 1 invasive ductal carcinoma (membranous staining) and classic invasive lobular carcinoma (cytoplasmic staining). The positivity rates for EMP1 and DVL1 in gradeI invasive ductal carcinoma were 95.8% (23/24) and 54.2% (13/24), respectively; while those in classic invasive lobular carcinoma were 12 and 5 cases, respectively.

CONCLUSIONS: E-cadherin and p120 catenin are useful immunomarkers for distinguishing between invasive ductal carcinoma and invasive lobular carcinoma. On the other hand, EMP1 and DVL1 are of limited value in this respect.}, } @article {pmid20078968, year = {2009}, author = {Yu, L and Yang, WT and Cai, X and Lu, HF and Fan, YZ and Shi, DR}, title = {[Clinicopathologic study of centrally necrotizing carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {10}, pages = {657-662}, pmid = {20078968}, issn = {0529-5807}, mesh = {Actins/metabolism ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma in Situ/metabolism/*pathology/surgery ; Carcinoma, Basal Cell/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; Keratin-14/metabolism ; Keratin-5/metabolism ; Lung Neoplasms/secondary ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Survival Rate ; }, abstract = {OBJECTIVE: To study the clinicopathologic features and immunophenotype of centrally necrotizing carcinoma (CNC) of breast; and to study its relationship with basal-like breast cancer.

METHODS: The clinical and pathologic characteristics of 35 cases of CNC were analyzed. Immunohistochemical study for estrogen receptor, progesterone receptor, HER2, CK8/18, 34betaE12, CK5/6, CK14, CK17, smooth muscle actin, p63, vimentin and epidermal growth factor receptor was performed using EnVision method. The surival information of 10 case were obtained.

RESULTS: The age of patients with CNC ranged from 30 to 82 years (mean = 54.2 years). Macroscopically, all tumors were relatively circumscribed, with a mean diameter of 2.4 cm. Histologically, there was a prominent central, necrotic or acellular zone surrounded by a narrow rim of viable tumor cells. The central necrotic foci had the following morphologic patterns: (1) coagulative tumor necrosis associated with various degree of fibrosis or hyaline degeneration (24 cases), (2) predominance of fibrous and scar tissue, with small amount of necrotic debris (8 cases), and (3) infarction (3 cases). The peripheral zone of tumor cells showed features of grade 3 invasive ductal carcinoma in 32 cases and grade 2 in 3 cases. Twenty cases of CNC were associated with ductal carcinoma in-situ. A component of invasive micropapillary carcinoma was identified in 5 cases. Peripheral lymphocytic infiltrates were seen in 17 cases. Immunohistochemical study of 31 cases showed that the expression rate of basal-like markers (83.9%, 26 cases) was higher than that of myoepithelial markers (38.7%, 12 cases). The percentage of basal-like subtype (64.5%, 20 cases) was higher than luminal-A (9.7%, 3 cases), luminal-B (9.7%, 3 cases), HER2 over-expression (12.9%, 4 cases) and null (3.2%, 1 case) subtypes. In 20 cases of basal-like carcinoma, the expression ratio of CK5/6 was highest amongst basal-like markers (18 cases), the other markers ratios of CK17, CK14 and epidermal growth factor receptor were 8/10, 14/19 and 8/16, respectively. Follow-up data were available in 10 patients. The follow-up duration ranged from 15 to 42 months (mean = 21.5 months). The median disease-free and overall survivals were 14.0 and 18.0 months, respectively. Disease progression (as defined by the presence of recurrence, metastasis or tumor-related death) occurred in 9 patients. The mean and median time to disease progression was 16.6 and 13.0 months, respectively.

CONCLUSIONS: CNC is a rare subtype of breast carcinoma and has distinctive, easily discernible morphologic features. The majority of CNC exhibits basal-like immunophenotype and carries a poor prognosis. CNC is the typical representative of basal-like breast cancer.}, } @article {pmid20075549, year = {2009}, author = {Ranade, KJ and Nerurkar, AV and Phulpagar, MD and Shirsat, NV}, title = {Expression of survivin and p53 proteins and their correlation with hormone receptor status in Indian breast cancer patients.}, journal = {Indian journal of medical sciences}, volume = {63}, number = {11}, pages = {481-490}, pmid = {20075549}, issn = {1998-3654}, mesh = {Adult ; Apoptosis/drug effects ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/immunology/pathology ; Carcinoma, Ductal, Breast/*genetics/immunology/pathology ; Female ; Fibroadenoma/genetics/immunology/pathology ; Humans ; Immunohistochemistry ; India ; Inhibitor of Apoptosis Proteins/*genetics ; Middle Aged ; Prognosis ; Receptors, Estrogen/*physiology ; Receptors, Progesterone/*physiology ; Retrospective Studies ; Statistics as Topic ; Statistics, Nonparametric ; Survivin ; Tumor Suppressor Protein p53/*genetics ; Young Adult ; }, abstract = {BACKGROUND: In invasive ductal carcinoma (IDC), many antiapoptotic and proapoptotic genes regulate disease outcome. Hormone receptor-mediated mechanisms have also been shown to prevent apoptosis. Therefore, relations between hormone receptor status and other molecular markers need further examination.

AIMS: In the present study, we analyzed the expression of apoptosis-regulating genes, viz., Survivin and mutant p53, in benign breast disease (fibroadenoma) and IDC patients. Results were then correlated with hormone receptor status of the patients.

MATERIAL AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with IDC and 32 female patients with fibroadenoma were used. Expression of Survivin and mutant p53 was evaluated using immunohistochemical staining method.

STATISTICAL ANALYSIS: Fisher exact test and nonparametric correlation test (Spearman rank correlation test) were performed. Results : In fibroadenoma, 53% of patients expressed Survivin and 13% of patients expressed p53 protein. Statistically significant increase in Survivin and p53 protein expression was observed in carcinoma cases. Survivin expression correlated negatively with progesterone receptor (PR) status, but its expression was independent of estrogen receptor (ER) status. p53 expression showed negative correlation with both ER and PR status.

CONCLUSIONS: Increased expression of Survivin and p53 in IDC patients and correlation with hormone receptors suggest that Survivin and p53 along with hormone receptors status are likely to contribute significantly to apoptosis resistance and may serve as therapeutic target that could increase the effectiveness of conventional breast cancer therapy.}, } @article {pmid20073613, year = {2010}, author = {Skripenova, S and Layfield, LJ}, title = {Initial margin status for invasive ductal carcinoma of the breast and subsequent identification of carcinoma in reexcision specimens.}, journal = {Archives of pathology & laboratory medicine}, volume = {134}, number = {1}, pages = {109-114}, doi = {10.5858/2008-0676-OAR1.1}, pmid = {20073613}, issn = {1543-2165}, mesh = {Biopsy ; Breast Neoplasms/pathology/*prevention & control/*surgery ; Carcinoma, Ductal, Breast/pathology/*prevention & control/*surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Neoplasm Recurrence, Local/epidemiology/pathology/*prevention & control ; Neoplasm, Residual/diagnosis/pathology ; Prevalence ; Retrospective Studies ; }, abstract = {CONTEXT: Margin status of lumpectomy specimens is related to frequency of local recurrence. Optimal surgical technique requires microscopic margins free of carcinoma by at least 2 mm. Recurrence following lumpectomy is associated with residual carcinoma secondary to inadequate resection.

OBJECTIVE: To review our series of breast excisions to determine the frequency of residual carcinoma for positive, close, and negative margins.

DESIGN: We reviewed lumpectomies and excisional biopsies for invasive ductal carcinoma that had subsequent reexcisions. Margin status of specimens was recorded as positive, less than 1 mm, 1 to 2 mm, or greater than 2 mm.

RESULTS: A total of 123 lumpectomies and excisional biopsies of invasive ductal carcinoma with reexcision were reviewed. Residual invasive carcinoma was found in 44% (17), 25% (6), 28% (8), and 16% (5) of cases with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively. Residual invasive carcinomas were found in 57% (8), 100% (5), 67% (2), and 100% (2) of mastectomies with positive, less than 1 mm, 1 to 2 mm, and greater than 2 mm margins, respectively, in the initial lumpectomy or excisional biopsy.

CONCLUSIONS: Frequency of residual invasive carcinoma was related to margin status of the original lumpectomy/biopsy. Even when margins were positive, most reexcisions were free of carcinoma. Residual invasive carcinoma was found in greater than 25% of patients with margins less than 2 mm, supporting reexcision for patients with margins of less than 2 mm. Sixteen percent of cases with margins greater than 2 mm harbored residual invasive carcinoma. Evaluation of margin status was complicated by tissue distortion and fragmentation.}, } @article {pmid20069058, year = {2009}, author = {Ziółkowski, P and Gamian, E and Osiecka, B and Zougman, A and Wiśniewski, JR}, title = {Immunohistochemical and proteomic evaluation of nuclear ubiquitous casein and cyclin-dependent kinases substrate in invasive ductal carcinoma of the breast.}, journal = {Journal of biomedicine & biotechnology}, volume = {2009}, number = {}, pages = {919645}, pmid = {20069058}, issn = {1110-7251}, mesh = {Antibodies, Neoplasm/immunology ; Antibody Specificity/immunology ; Breast Neoplasms/immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast/immunology/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Nuclear Proteins/immunology/*metabolism ; Phosphoproteins/immunology/*metabolism ; *Proteomics ; }, abstract = {Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as structure of its DNA binding domain resembles that of high-mobility group A, HMGA proteins. HMGA proteins are associated with various malignancies. Since changes in expression of HMGA are considered as marker of tumor progression, it is possible that similar changes in expression of NUCKS could be useful tool in diagnosis and prognosis of breast cancer. For identification and analysis of NUCKS we used proteomic and histochemical methods. Analysis of patient-matched samples of normal and breast cancer by mass spectrometry revealed elevated levels of NUCKS in protein extracts from ductal breast cancers. We elicited specific antibodies against NUCKS and used them for immunohistochemistry in invasive ductal carcinoma of breast. We found high expression of NUCKS in 84.3% of cancer cells. We suggest that such overexpression of NUCKS can play significant role in breast cancer biology.}, } @article {pmid20063683, year = {2009}, author = {Chelli, D and Dimassi, K and Salem, A and Driss, M and Zaanouni, E and Zouaoui, B and Sfar, E and Ben Aissa, R and Chelli, H and Chennoufi, BM and Boussen, H}, title = {[Surgical treatment of breast lesions: preliminary results of the screening program of the Ariana area].}, journal = {La Tunisie medicale}, volume = {87}, number = {7}, pages = {475-479}, pmid = {20063683}, issn = {0041-4131}, mesh = {Adult ; Breast Neoplasms/diagnosis/*surgery ; Female ; Humans ; Mammography ; Mass Screening ; Middle Aged ; Retrospective Studies ; Tunisia ; }, abstract = {OBJECTIVE: To report clinical, radiological and histological characteristics of the infraclinical breast lesions patients recruited via the large scale mammography breast cancer screening of l'Ariana state in Tunisia.

MATERIALS AND METHODS: Retrospective study over a period of 2 years. The recruitment of patients made on the occasion of the program of breast cancer screening.

RESULTS: During this period, 22 patients in our unity had had a surgical excision after wire localization. Ten patients were recruited by means of systematic breast cancer screening. In these cases, the mammographic findings were classified B.I.R.A.D.S 4 in 7 cases and BIRADS type 5 in 3 cases. Definitive histology concluded to benign disease in 4 cases and malignancy 6 cases. This collaboration enables the diagnosis an invasive ductal carcinoma in three cases.

CONCLUSION: The surgical excision after wire localization for non palpable breast lesions allows diagnosis of high-risk benign lesions and low-stage breast cancer. It is a reliable technique which indications have to be based on clinical and radiological strict criteria. This procedure is at present, and in developed countries, widely outstripped with the stereotactic core needle biopsy.}, } @article {pmid20063680, year = {2009}, author = {Mehiri, S and Arous, Y and Salem, A and Bouchlaka, A and Kribi, L and Sellemi, M and Hamza, R and Mnif, N and Gueddana, N}, title = {[Lesions classified ACR3 with the breast cancer screening mammography program of the Ariana area: features and problems encountered].}, journal = {La Tunisie medicale}, volume = {87}, number = {7}, pages = {458-462}, pmid = {20063680}, issn = {0041-4131}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Female ; Humans ; *Mammography ; *Mass Screening ; Middle Aged ; Retrospective Studies ; Tunisia ; }, abstract = {OBJECTIVE: This retrospective work is related to ACR3 mammograms of the program "Feasibility of breast cancer screening by mammography in Ariana Governorate" in order to evaluate the efficiency and short-term quality control of these probably benign lesions.

MATERIALS AND METHODS: Mammograms classified ACR3 raised the indication of further examination, futher mammogram (profile, expanded or compression). The monitoring and control period are explained to the patient by the radiologist.

RESULTS: 6.6% mammograms were classified as ACR 3 with 71.3% under the age of 50 years. Breast is very dense in 20.5% of cases, and transparent in 6% of cases. Further exams has been performed in 94. 5% of cases with a profile in 52% of cases, enlarged in 22.1%, compression in 24.9% and ultrasound in 82.5%. The surveillance protocol was insufficient for 126 women lost to the 1st control, 32 women lost for the 2nd control and 19 women were lost to the 3rd control. After two years monitoring, 219 women were reclassified as ACR2 with a negative test. In 2 patients, we found an invasive ductal carcinoma at 4 months control.

CONCLUSION: ACR 3 mammograms are the most important operator dependent category. The diagnosis of probably benign lesion dependant of the analysis of images and requires a great experience of the radiologist and a comprehensive complementary examination. In this study, this assessment was often heavy in relation to the frequency of dense breasts itself in connection with the young age of patients. In addition, for this particular category, the need of training is important and in terms of public health cost, the management of ACR3 mammograms increases difficulties and cost of screening.}, } @article {pmid20060718, year = {2010}, author = {McAree, B and O'Donnell, ME and Spence, A and Lioe, TF and McManus, DT and Spence, RA}, title = {Breast cancer in women under 40 years of age: a series of 57 cases from Northern Ireland.}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {2}, pages = {97-104}, doi = {10.1016/j.breast.2009.12.002}, pmid = {20060718}, issn = {1532-3080}, mesh = {Adult ; Breast Neoplasms/genetics/*pathology/*physiopathology/therapy ; Female ; Genetic Predisposition to Disease ; Humans ; Neoplasm Staging ; Northern Ireland/epidemiology ; Retrospective Studies ; }, abstract = {BACKGROUND: There are few studies examining breast cancer in women under the age of 40 years, particularly in western European populations. Such tumours are reported to be more aggressive, possibly due to a different pathophysiology compared to older patients.

METHODS: We performed a retrospective review of all women less than 40 years of age, diagnosed or treated with breast cancer, from June 2001 to June 2007 to assess pathophysiological factors that may influence clinical outcome and prognosis including patient demographics, clinical presentation, pre-operative investigations, surgical and pathological findings, treatment and outcome.

RESULTS: Fifty-eight women (mean age 34.9 years, range 27-39 years) were identified. One patient was excluded due to incomplete data; 98.2% (n=56) patients presented directly to our symptomatic clinic; 89.5% (n=51) patients had a palpable lump; 71.9% (n=41) patients had no family history. Mammography was less sensitive than ultrasound (64.3% vs. 82.4%) while fine needle aspiration cytology was 92.5% sensitive for malignancy. Twenty-nine (50.9%) patients underwent breast-conserving surgery (BCS) of which 7 proceeded subsequently to completion mastectomy due to involved margins. Twenty-six (45.6%) patients required total mastectomy primarily while 2 (3.5%) patients were treated palliatively due to metastatic disease. The mean tumour size (nearest resection margin) was 2.13cm (2.58mm) for BCS and 3.95cm (6.38mm) for mastectomy. From a total of 55 primary resections, 85.5% (n=47) of tumours were invasive ductal carcinoma; 57.4% (n=31) and 40.7% (n=22) were grade II and III tumours respectively. Lymphovascular invasion was identified in 50.9% (n=28) while 40.0% (n=22) were lymph node positive for metastatic disease. 76.8% (n=43), 39.3% (n=22) and 30.2% (n=16) were oestrogen, progesterone and human epidermal growth factor receptor-2 positive respectively. The mean Nottingham prognostic index was 4.37 (range 2.2-8.4). Neo-adjuvant and adjuvant chemotherapy was administered to 9.3% (n=5) and 80.0% (n=44) of surgically treated patients respectively while 76.4% (n=42) patients received adjuvant radiotherapy. 76.4% (n=42) of patients were treated with tamoxifen. Four patients received Herceptin therapy. Statistically significant univariate factors adversely associated with overall survival were time from referral to out-patient department attendance (p=0.038), administration of neo-adjuvant treatment (p=0.019), surgical intervention (p<0.001), progesterone receptor positivity (p=0.018) and tumour recurrence (p<0.001). 86.0% (n=49) patients were alive at mean follow-up of 52 months; 82.5% (n=47) remain disease free.

CONCLUSION: Our study reports a low familial trait rate combined with a high proportion of hormonally active tumours less than grade III which suggests that breast cancer in this series of young women from Northern Ireland may be less aggressive and more hormonally responsive than anticipated.}, } @article {pmid20060154, year = {2010}, author = {Hasebe, T and Okada, N and Iwasaki, M and Akashi-Tanaka, S and Hojo, T and Shibata, T and Sasajima, Y and Tsuda, H and Kinoshita, T}, title = {Grading system for lymph vessel tumor emboli: significant outcome predictor for invasive ductal carcinoma of the breast.}, journal = {Human pathology}, volume = {41}, number = {5}, pages = {706-715}, doi = {10.1016/j.humpath.2009.10.015}, pmid = {20060154}, issn = {1532-8392}, mesh = {Breast Neoplasms/*classification/mortality/*pathology ; Carcinoma, Ductal, Breast/*classification/mortality/*pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Lymphatic Vessels/pathology ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; }, abstract = {The purpose of this study was to confirm that the grading system for lymph vessel tumor emboli is a significant histologic outcome predictor for patients with invasive ductal carcinoma. The subjects of this study were 1042 invasive ductal carcinoma patients who did not receive neoadjuvant therapy. We classified all invasive ductal carcinomas according to the grading system for lymph vessel tumor emboli we devised, and performed multivariate analyses with well-known prognostic factors. Of 1042 carcinomas, 666, 250, 97, and 29 were classified according to the grading system for lymph vessel tumor emboli as grade 0 (no lymph vessel invasion), grade 1, grade 2, and grade 3, respectively. The univariate analyses showed that the difference in outcome between the group with grade 0 and the group with grade 1 was not significant, but that survival time was significantly shorter in the group of patients with grade 2 carcinomas than in the group with grade 1 carcinomas and significantly shorter in the group of patients with grade 3 carcinomas than in the group with grade 2 carcinomas. Multivariate analyses demonstrated that having a grade 2 or grade 3 carcinoma significantly increased the hazard rates for tumor recurrence and tumor-related death in the patients as a whole as well as in both the group of patients with nodal metastasis and the group without nodal metastasis. The grading system for lymph vessel tumor emboli is an excellent histologic grading system for predicting the outcome of patients with invasive ductal carcinoma of the breast.}, } @article {pmid20060146, year = {2010}, author = {Sadakari, Y and Ohuchida, K and Nakata, K and Ohtsuka, T and Aishima, S and Takahata, S and Nakamura, M and Mizumoto, K and Tanaka, M}, title = {Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type.}, journal = {Surgery}, volume = {147}, number = {6}, pages = {812-817}, doi = {10.1016/j.surg.2009.11.011}, pmid = {20060146}, issn = {1532-7361}, mesh = {Aged ; Analysis of Variance ; Carcinoma, Pancreatic Ductal/mortality/*pathology/*surgery ; Carcinoma, Papillary/mortality/*pathology ; Female ; Humans ; Intestinal Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; Pancreatectomy/methods/mortality ; Pancreatic Juice/cytology ; Pancreatic Neoplasms/classification/mortality/*pathology/*surgery ; Pancreaticoduodenectomy/methods/mortality ; Prognosis ; Pylorus/surgery ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is divided into 4 subtypes: an intestinal type, a gastric type, a pancreatobiliary type, and an oncocytic type. The purposes of this study were to clarify the outcomes and the characteristics of invasive carcinoma derived from IPMN (invasive IPMC) by focusing on these subtypes with a comparison to conventional invasive ductal carcinoma (IDC) of the pancreas.

METHODS: A total of 30 patients with invasive IPMC were reviewed, and the tumors were divided into 2 pathologic subtypes, intestinal and nonintestinal type. The prognosis and characteristics of the 2 subtypes were evaluated. Furthermore, the prognosis of 119 patients with conventional IDC was compared with that of patients with invasive carcinoma derived from the intestinal or nonintestinal type IPMN.

RESULTS: The 5-year survival rate of patients with the nonintestinal type (0.0%) was as poor as that of patients with conventional IDC (19.9%; P = .67). The patients with the intestinal type (66.7%) had a more favorable prognosis than patients with conventional IDC (P < .001). The nonintestinal type was characterized by positive lymphatic invasion and tubular invasive pattern.

CONCLUSION: Invasive carcinoma derived from the nonintestinal type IPMN characterized by lymphatic invasion and tubular invasive pattern is associated with a poor prognosis.}, } @article {pmid20052393, year = {2009}, author = {Streckfus, CF and Storthz, KA and Bigler, L and Dubinsky, WP}, title = {A Comparison of the Proteomic Expression in Pooled Saliva Specimens from Individuals Diagnosed with Ductal Carcinoma of the Breast with and without Lymph Node Involvement.}, journal = {Journal of oncology}, volume = {2009}, number = {}, pages = {737619}, pmid = {20052393}, issn = {1687-8469}, abstract = {Purpose. The objective was to compare the salivary protein profiles of saliva specimens from individuals diagnosed with invasive ductal carcinoma of the breast (IDC) with and without lymph node involvement. Methods. Three pooled saliva specimens from women were analyzed. One pooled specimen was from healthy women; another was from women diagnosed with Stage IIa IDC and a specimen from women diagnosed with Stage IIb. The pooled samples were trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase capillary chromatography on an LC-MS/MS mass spectrometer. Results. The results yielded approximately 174 differentially expressed proteins in the saliva specimens. There were 55 proteins that were common to both cancer stages in comparison to each other and healthy controls while there were 20 proteins unique to Stage IIa and 28 proteins that were unique to Stage IIb.}, } @article {pmid20050885, year = {2010}, author = {Barone, P}, title = {Neurotransmission in Parkinson's disease: beyond dopamine.}, journal = {European journal of neurology}, volume = {17}, number = {3}, pages = {364-376}, doi = {10.1111/j.1468-1331.2009.02900.x}, pmid = {20050885}, issn = {1468-1331}, mesh = {Animals ; Dopamine/metabolism ; Humans ; Parkinson Disease/*physiopathology ; Synaptic Transmission/*physiology ; }, abstract = {Parkinson's disease (PD) is most frequently associated with characteristic motor symptoms that are known to arise with degeneration of dopaminergic neurons. However, patients with this disease also experience a multitude of non-motor symptoms, such as sleep disturbances, fatigue, apathy, anxiety, depression, cognitive impairment, dementia, olfactory dysfunction, pain, sweating and constipation, some of which can be at least as debilitating as the movement disorders and have a major impact on patients' quality of life. Many of these non-motor symptoms may be evident prior to the onset of motor dysfunction. The neuropathology of PD has shown that complex, interconnected neuronal systems, regulated by a number of different neurotransmitters in addition to dopamine, are involved in the aetiology of motor and non-motor symptoms. This review focuses on the non-dopaminergic neurotransmission systems associated with PD with particular reference to the effect that their modulation and interaction with dopamine has on the non-motor symptoms of the disease. PD treatments that focus on the dopaminergic system alone are unable to alleviate both motor and non-motor symptoms, particularly those that develop at early stages of the disease. The development of agents that interact with several of the affected neurotransmission systems could prove invaluable for the treatment of this disease.}, } @article {pmid20043090, year = {2010}, author = {Logullo, AF and Nonogaki, S and Pasini, FS and Osório, CA and Soares, FA and Brentani, MM}, title = {Concomitant expression of epithelial-mesenchymal transition biomarkers in breast ductal carcinoma: association with progression.}, journal = {Oncology reports}, volume = {23}, number = {2}, pages = {313-320}, pmid = {20043090}, issn = {1791-2431}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/mortality/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*metabolism/mortality/*pathology ; Cell Transformation, Neoplastic/*metabolism/pathology ; Disease Progression ; Epithelium/pathology ; Female ; Humans ; Mesoderm/pathology ; Middle Aged ; Survival Analysis ; Tissue Array Analysis ; }, abstract = {Epithelial to mesenchymal transition (EMT) is a process implicated in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. We determined the expression of some putative EMT biomarkers including E-cadherin, beta-catenin, zinc finger factor Snail (Snail), transforming growth factor beta1 (TGFbeta1), TGFbeta type II receptor (TBRII) and the HGF receptor (c-met) and their possible correlation to progression and overall survival in a series of breast ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). Biomarkers were immunohistochemically determined in 55 IDC specimens from which 21 had lymph node metastases and in 95 DCIS specimens, 46 of these cases associated to invasive carcinoma, in a tissue microarray (TMA). Positive cytoplasmic staining of TGFbeta1 (78.2%), c-met (43.6%), Snail (34.5%), TBRII (100%), membranous E-cadherin (74.5%) and membranous/cytoplasmic beta-catenin (71%) were detected in the IDC samples. Metastatic lymph node samples displayed similar frequencies. A significant increase of c-met and TGFbeta1 positivity along DCIS to IDC progression was noted but only TGFbeta1 positivity was associated with presence of lymph node metastases and advanced stages in IDC. The evaluation of the other EMT markers in DCIS did not show differences in positivity rate as compared to invasive carcinomas. DCIS either pure or associated to IDC showed similar expression of the analyzed biomarkers. All the carcinomas exhibited positive expression of TBRII. Associations between the markers, determined by Spearman's correlation coefficient, showed a significant association between TGFbeta1 and respectively E-cadherin, beta-catenin and c-met in DCIS cases, but in invasive carcinomas only cadherin and catenin were positively correlated. Kaplan-Meier survival curves revealed that none of the EMT biomarkers analyzed were correlated with survival, which was significantly determined only by clinical and hormone receptor parameters.}, } @article {pmid20037463, year = {2009}, author = {Sakurai, K and Fujisaki, S and Matsuo, S and Ogura, M and Enomoto, K and Kitajima, A and Tani, M and Amano, S and Shiono, M}, title = {[A case of advanced breast cancer with skin ulceration successfully treated with paclitaxel and toremifene therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {12}, pages = {2484-2486}, pmid = {20037463}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Breast Neoplasms/complications/*drug therapy ; Carcinoma, Ductal, Breast/complications/*drug therapy ; Female ; Hemorrhage/*complications/*etiology ; Humans ; Organic Chemicals/administration & dosage ; Paclitaxel/*administration & dosage ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Skin Ulcer/*etiology ; }, abstract = {We report a case of advanced breast cancer with skin ulceration and bleeding (T4bN3bM0, Stage IIIC) achieving a significant improvement of QOL by paclitaxel (PTX) and toremifene (TOR) therapy. The patient was a 31-year-old woman who had ulcerative breast lump with skin ulcer. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and negative for HER2/neu protein expression. She received 4 courses of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2/tri-weekly) and 4 courses of weekly PTX (80 mg/m2) with TOR (120 mg/day). The bleeding from the tumor disappeared after CEF chemotherapy. The response for breast tumor after PTX and TOR therapy was evaluated as partial response, and the infraclavicular, subpectoral, and interpectoral lymph nodes metastasis disappeared. Muscle-preserving radical mastectomy (Bt+Ax: Auchincloss) without skin transplantation were performed. She had no recurrence during one year after operation. PTX and TOR therapy were effective for advanced breast tumor, and can improve patient QOL and the clinical outcomes in Stage IIIC advanced breast cancer.}, } @article {pmid20037460, year = {2009}, author = {Aoyagi, H and Kaneko, J and Makinose, T and Someno, Y and Katsuta, E and Saguchi, M and Okubo, K and Hamada, S and Sekine, T and Sato, T and Sugihara, K and Maejima, S}, title = {[A case of stage IV breast cancer responding to S-1 therapy after FEC and PTX therapies].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {12}, pages = {2474-2476}, pmid = {20037460}, issn = {0385-0684}, mesh = {Adult ; Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use ; Antineoplastic Agents, Phytogenic/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal/*drug therapy ; Cyclophosphamide/therapeutic use ; Drug Combinations ; Epirubicin/therapeutic use ; Female ; Fluorouracil/therapeutic use ; Humans ; Oxonic Acid/administration & dosage/*therapeutic use ; Paclitaxel/therapeutic use ; Pentoxifylline/therapeutic use ; Quality of Life ; Tegafur/administration & dosage/*therapeutic use ; Treatment Outcome ; }, abstract = {In November 2005, a 34-year-old female presented to our department with a bleeding tumor on her right breast. She noticed the tumor approximately two years ago but she left it untreated. An exposed tumor was observed with a diameter of approximately 8 cm located in the right breast. It was diagnosed as invasive ductal carcinoma by biopsy (ER (+), PgR (+), and HERS2: 1 +). The imaging showed multiple metastases to the bilateral lungs, right axillary lymph node, mediastinal lymph node and sternal. The diagnosis was made as right breast cancer (T4c, N3c, M1, and stage IV). The patient received 4 courses of FEC therapy and 4 courses of PTX therapy. The patient had a partial response (PR). However, tumor markers were elevated in September 2006. Thus, an administration of S-1 was initiated. The size of the tumor shown in the imaging was reduced, and the patient had a PR. Since December 2008, tumor markers have been elevated again. However, the patient has had SD in the imaging and S-1 administrations have been continued. A total of 24 courses have been performed to the present time, and the patient's conditions have not been aggravated in approximately 3 years and 5 months. She has maintained a good QOL and is being followed up on an outpatient basis. S-1 administrations can be an effective treatment for advanced breast cancer resistant to anthracycline and taxane when considering a satisfactory QOL of patients.}, } @article {pmid20037447, year = {2009}, author = {Matsumura, T and Ohzato, H and Yamamoto, T and Ota, K and Mabuchi, E and Miwa, H and Ikeda, H and Fukunaga, M and Furukawa, H}, title = {[A case of postoperative brain metastasis originated from pancreatic cancer which was successfully treated by resection and postoperative irradiation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {12}, pages = {2433-2435}, pmid = {20037447}, issn = {0385-0684}, mesh = {Antimetabolites, Antineoplastic/therapeutic use ; Brain Neoplasms/*secondary/*therapy ; Carcinoma, Ductal/*pathology ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Drug Combinations ; Humans ; Male ; Middle Aged ; Oxonic Acid/administration & dosage ; Pancreatic Neoplasms/*pathology ; Tegafur/administration & dosage ; Gemcitabine ; }, abstract = {We report a case of metastatic brain tumor originated from pancreatic cancer, which might be clinically considered as rare and has been reported as a remarkably poor-prognostic disease. A 64-year-old male underwent pancreas tail resection for pancreatic cancer (R0 resection). Histological study revealed an invasive ductal carcinoma (T4N2M0, fStage IVb). Following a short term of GEM administration, S-1 (80 mg/m2,day 1-28/42 days) was administered as the second-line. After 7 courses of S-1 chemotherapy, a follow-up CT demonstrated lymph node recurrence in cervical and mediastinum region. S-1 administration was stopped and irradiation to these sites (60 Gy) resulted in PR. Two months after irradiation, dizziness and speech disturbance appeared, and MRI examination demonstrated a solitary brain metastasis, which was removed because of rapid worseness of neurological symptoms. Postoperatively, hemicereberal irradiation (30 Gy) was performed. After the brain surgery, no brain metastasis was appeared. The patient was alive with abdominal lymph node recurrence for 22 months after distal pancreatectomy. It was concluded from these findings that irradiation to systemic recurrence originated from pancreatic cancer might be effective as well as chemotherapy.}, } @article {pmid20037338, year = {2009}, author = {Sakurai, K and Fujisaki, S and Matsuo, S and Ogura, M and Enomoto, K and Kitajima, A and Tani, M and Amano, S and Shiono, M}, title = {[Treatment strategy of breast carcinoma in the elderly patient-surgery, hormone therapy, and chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {12}, pages = {2105-2107}, pmid = {20037338}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Combined Modality Therapy ; Female ; Humans ; }, abstract = {We report an elderly breast carcinoma patient with complication. The patient was a 91-year-old woman who had breast lump. The tumor was 3 cm in diameter. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesterone receptor, and positive for HER2/neu protein expression. She received tumorectomy. After operation, she was administered aromatase inhibitor. After six months from operation, metastases of lymph nodes and lung were observed. Although she had administered another aromatase inhibitor, the metastases were rapidly growing. Eight months after operation, she died from carcinomatous lymphangitis. Even the less invasive operation by local anesthesia can progress metastases rapidly in elderly breast cancer patients. This case suggested that a treatment strategy for elderly breast cancer patients should have been determined carefully.}, } @article {pmid20036907, year = {2010}, author = {Barok, M and Balazs, M and Lazar, V and Rakosy, Z and Toth, E and Treszl, A and Vereb, G and Colbern, GT and Park, JW and Szollosi, J}, title = {Characterization of a novel, trastuzumab resistant human breast cancer cell line.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {2}, number = {2}, pages = {627-640}, doi = {10.2741/e119}, pmid = {20036907}, issn = {1945-0508}, support = {P50 CA58207/CA/NCI NIH HHS/United States ; R03 TW 00871-01A2/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; *Cell Line, Tumor ; Comparative Genomic Hybridization ; *Disease Models, Animal ; *Drug Resistance, Neoplasm ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Mice ; Mice, SCID ; Oncogenes/genetics ; Receptor, ErbB-2/metabolism ; Trastuzumab ; }, abstract = {HER2-positive breast cancers represent a distinct phenotype and are intrinsically more aggressive than HER2-negative tumors. Although HER2-targeted therapies have been rationally developed, resistance to these treatments represents a process understood poorly. There are few experimental models that allow studying the molecular mechanism of resistance. Our aim was to characterize a trastuzumab resistant breast cancer cell line (B585) that was established from an invasive ductal carcinoma. B585 grows only in immunodeficient mice as a xenograft. CGH and FISH were used to define cytogenetic alterations, gene-expression analysis and immunohistochemistry were applied to detect RNA and protein expression. By array-CGH focused amplifications were identified for C-MYC, EGFR, ErbB2, CCND1 and TOP2-A oncogenes. ErbB2 was co-amplified with TOP2-A. mRNA overexpression was detected for the amplified genes. ErbB2 protein was overexpressed and showed heterogeneous distribution. In summary, molecular cytogenetic analysis and expression profiling of B585 revealed several new alterations. Based on the experiments performed in SCID mice and the genotypic/phenotypic characteristics, this new in vivo breast cancer xenograft is a valuable model to investigate molecular mechanism of trastuzumab resistance.}, } @article {pmid20035293, year = {2009}, author = {Tsukuda, K and Tsuji, H and Kunitomo, T and Aokage, K and Miyake, T and Nakahara, S and Masuda, H}, title = {Breast cancer with cartilaginous and/or osseous metaplasia diagnosed by lymph nodal metastasis: a case report.}, journal = {Acta medica Okayama}, volume = {63}, number = {6}, pages = {367-371}, doi = {10.18926/AMO/31828}, pmid = {20035293}, issn = {0386-300X}, mesh = {Bone and Bones/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Cartilage/pathology ; Fatal Outcome ; Female ; Humans ; Lymphatic Metastasis/*pathology ; Metaplasia/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Phyllodes Tumor/pathology ; }, abstract = {Breast cancer with cartilaginous and/or osseous metaplasia is a type of metaplastic carcinomas and is a rare disease. We report the case of a 49 year-old female who underwent right mastectomy for a large breast tumor. Histological examinations revealed a mixed tumor with both stromal and epithelial elements;the stroma showed poor differentiated spindle-shape and multiform cells with a massive osseous matrix, and atypical epithelial cells, which mainly existed on the surface of the cysts, showed nucleic atypia. The tumor was diagnosed as a malignant phyllodes tumor with osteosarcomatous differentiation;it was not identified as a metaplastic carcinoma because of the lack of proof of a cancerous component. Two years after a mastectomy, swelling of the axillary lymph nodes was found and a biopsy was performed. Histological findings for the lymph node indicated a metastasis of the invasive ductal carcinoma. The primary tumor was re-examined and was considered to be the origin of the lymph nodal metastasis. Lymph nodal metastasis of cancer proved that the primary tumor had cancerous potential, and the pathological diagnosis was altered to a breast cancer with cartilaginous and/or osseous metaplasia.}, } @article {pmid20029735, year = {2010}, author = {Vantorre, J and Seifert, L and Fernandes, RJ and Boas, JP and Chollet, D}, title = {Kinematical profiling of the front crawl start.}, journal = {International journal of sports medicine}, volume = {31}, number = {1}, pages = {16-21}, doi = {10.1055/s-0029-1241208}, pmid = {20029735}, issn = {1439-3964}, mesh = {Adolescent ; Adult ; Athletic Performance/*physiology ; Biomechanical Phenomena ; Cluster Analysis ; Humans ; Male ; Swimming/*physiology ; Young Adult ; }, abstract = {This study analysed the start phases of 15 elite front crawl swimmers, all specialists of sprint events. The first aim was to determine which phases were correlated with the 15-m start time. The features common to the sample of swimmers were then established and individual profiles were clustered. The subjects performed two 25-m trials at the 50-m race-pace using their preferential start technique (grab start). The kinematical analysis assessed the durations of the block, flight, entry, glide, leg kicking and full swimming phases to the 15-m mark. Stroking parameters and the index of arm coordination (IdC) were analysed for the swimming part (10-20 m) of the 25-m. Through the swimming part IdC increased while stroke length and velocity decreased (p<0.05). The relative durations of the aerial (block, flight), entry and underwater phases were correlated with start time. Inter-subject variability was observed, which suggests that various motor solutions were used for the start. Notably, four clusters led to a short 15-m start time: the leg kicking style, mixed "leg kicking/swimming" style, long glide style and short glide style.}, } @article {pmid20027472, year = {2009}, author = {Portella, RS and Andrade, SG}, title = {Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice.}, journal = {Memorias do Instituto Oswaldo Cruz}, volume = {104}, number = {7}, pages = {1023-1030}, doi = {10.1590/s0074-02762009000700015}, pmid = {20027472}, issn = {1678-8060}, mesh = {Animals ; Antibodies, Monoclonal/blood ; Antigens, Protozoan/*analysis/drug effects ; Chagas Cardiomyopathy/drug therapy/*immunology/pathology ; Dendritic Cells/*immunology/pathology ; Disease Models, Animal ; Drug Resistance ; Mice ; Myocarditis/drug therapy/*immunology/pathology ; Myocardium/*cytology/immunology ; Nitroimidazoles/therapeutic use ; Time Factors ; Trypanocidal Agents/therapeutic use ; Trypanosoma cruzi/classification/*immunology ; }, abstract = {We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.}, } @article {pmid20024808, year = {2009}, author = {Koborova, ON and Filimonov, DA and Zakharov, AV and Lagunin, AA and Ivanov, SM and Kel, A and Poroikov, VV}, title = {In silico method for identification of promising anticancer drug targets.}, journal = {SAR and QSAR in environmental research}, volume = {20}, number = {7-8}, pages = {755-766}, doi = {10.1080/10629360903438628}, pmid = {20024808}, issn = {1029-046X}, mesh = {Antineoplastic Agents/*chemistry/*pharmacology ; Breast Neoplasms/*drug therapy ; Computer Simulation ; Female ; Gene Expression Regulation/drug effects ; Humans ; Proteins/antagonists & inhibitors ; Quantitative Structure-Activity Relationship ; }, abstract = {In recent years, the accumulation of the genomics, proteomics, transcriptomics data for topological and functional organization of regulatory networks in a cell has provided the possibility of identifying the potential targets involved in pathological processes and of selecting the most promising targets for future drug development. We propose an approach for anticancer drug target identification, which, using microarray data, allows discrete modelling of regulatory network behaviour. The effect of drugs inhibiting a particular protein or a combination of proteins in a regulatory network is analysed by simulation of a blockade of single nodes or their combinations. The method was applied to the four groups of breast cancer, HER2/neu-positive breast carcinomas, ductal carcinoma, invasive ductal carcinoma and/or a nodal metastasis, and to generalized breast cancer. As a result, some promising specific molecular targets and their combinations were identified. Inhibitors of some identified targets are known as potential drugs for therapy of malignant diseases; for some other targets we identified hits in the commercially available sample databases.}, } @article {pmid20018726, year = {2009}, author = {Hermes, GL and Delgado, B and Tretiakova, M and Cavigelli, SA and Krausz, T and Conzen, SD and McClintock, MK}, title = {Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {106}, number = {52}, pages = {22393-22398}, pmid = {20018726}, issn = {1091-6490}, support = {T32 MH019961/MH/NIMH NIH HHS/United States ; BC 061754/BC/NCI NIH HHS/United States ; R25 MH071584/MH/NIMH NIH HHS/United States ; T32HD009007/HD/NICHD NIH HHS/United States ; T32MH19961/MH/NIMH NIH HHS/United States ; P50 ES012382/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal ; Breast Neoplasms/etiology ; Carcinoma, Ductal, Breast/etiology ; Carcinoma, Intraductal, Noninfiltrating/etiology ; Corticosterone/metabolism ; Endocrine Glands/physiopathology ; Female ; Humans ; Mammary Neoplasms, Experimental/*etiology/pathology/physiopathology/*psychology ; Ovary/physiopathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/metabolism ; Risk Factors ; Social Environment ; *Social Isolation ; Stress, Physiological ; Stress, Psychological ; }, abstract = {In a life span study, we examined how the social environment regulates naturally occurring tumor development and malignancy in genetically prone Sprague-Dawley rats. We randomly assigned this gregarious species to live either alone or in groups of five female rats. Mammary tumor burden among social isolates increased to 84 times that of age-matched controls, as did malignancy, specifically a 3.3 relative risk for ductal carcinoma in situ and invasive ductal carcinoma, the most common early breast cancers in women. Importantly, isolation did not extend ovarian function in late middle age; in fact, isolated animals were exposed to lower levels of estrogen and progesterone in the middle-age period of mammary tumor growth, with unchanged tumor estrogen and progesterone receptor status. Isolates, however, did develop significant dysregulation of corticosterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age. Among isolates, corticosterone response to an acute stressor was enhanced and recovery was markedly delayed, each associated with increased mammary tumor progression. In addition to being stressed and tumor prone, an array of behavioral measures demonstrated that socially isolated females possessed an anxious, fearful, and vigilant phenotype. Our model provides a framework for studying the interaction of social neglect with genetic risk to identify mechanisms whereby psychosocial stressors increase growth and malignancy of breast cancer.}, } @article {pmid20018297, year = {2011}, author = {Horimoto, Y and Tokuda, E and Arakawa, A and Kosaka, T and Saito, M and Kasumi, F}, title = {Significance of HER2 protein examination in ductal carcinoma in situ.}, journal = {The Journal of surgical research}, volume = {167}, number = {2}, pages = {e205-10}, doi = {10.1016/j.jss.2009.07.030}, pmid = {20018297}, issn = {1095-8673}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Biopsy ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Invasiveness/pathology ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*metabolism ; Retrospective Studies ; }, abstract = {BACKGROUND: HER2 expression is routinely checked in ductal carcinoma in situ, as in invasive ductal carcinoma. However, the effect of HER2 status in ductal carcinoma in situ on the development of malignancy and the significance of overexpression of HER2 are still not clear.

MATERIALS AND METHODS: We experienced 103 cases that were diagnosed as pure ductal carcinoma in situ from operative specimens in the 2-y period from 2006 to 2007. We examined their HER2 status and other markers. We added 38 cases of ductal carcinoma in situ with small invasive disease 5mm or less in diameter as subjects. We also examined how accurately HER2 status in biopsy specimens predicted the existence of an invasive component.

RESULTS: In pure ductal carcinoma in situ, tumors that were comedo type, high grade, or ER negative showed a high frequency of HER2 overexpression. In cases with small invasion, HER2 expression was higher than that in pure ductal carcinoma in situ. Among cases that were diagnosed as ductal carcinoma in situ by biopsy, 28% had invasive disease in operative specimens. In tumors that were palpable, large, or expressed HER2 3+ in biopsy samples, invasive disease was frequently observed in operative specimens.

CONCLUSIONS: Overexpression of HER2 in ductal carcinoma in situ might not always be necessary for progression to invasive ductal carcinoma. To clarify the significance of HER2 examination in DCIS, further investigations of the potential for invasive ductal carcinoma and the prognosis are still needed.}, } @article {pmid20015931, year = {2011}, author = {El-Ghannam, DM and Arafa, M and Badrawy, T}, title = {Mutations of p53 gene in breast cancer in the Egyptian province of Dakahliya.}, journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners}, volume = {17}, number = {2}, pages = {119-124}, doi = {10.1177/1078155209356130}, pmid = {20015931}, issn = {1477-092X}, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma/genetics/metabolism/pathology ; Codon, Nonsense ; DNA Mutational Analysis ; Egypt ; Exons ; Female ; Frameshift Mutation ; *Genes, p53 ; Genetic Association Studies ; Humans ; Middle Aged ; *Mutation ; Mutation, Missense ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Polymerase Chain Reaction ; *Polymorphism, Single-Stranded Conformational ; Tumor Burden ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy among females worldwide. Molecular analysis of p53 is likely to have value in diagnosis, prognosis, and treatment of breast cancer.

OBJECTIVE: To study the frequency and spectrum of p53 gene mutations in breast cancer patients residing Al Dakahliya district in the north of Egypt.

MATERIALS AND METHODS: Thirty patients with cancer breast as well as 10 controls were evaluated for p53 status by flow-cytometry, PCR-SSCP, and sequencing analysis.

RESULTS: P53 mutations were evident in five breast cancer patients (17%) including two missense mutations (A218 T and R279 G) in exon 6, 8; nonsense mutations (S297stop and Y159stop) in exon 8, 5, respectively, and frame shift mutation (M133 fs) in exon 5. p53 mutations were associated with invasive ductal carcinoma, large tumor size, and advanced disease stage

CONCLUSION: p53 gene mutations is potentially responsible for pathogenesis and clinical aggressiveness of breast cancer in our locality.}, } @article {pmid20015349, year = {2009}, author = {Westenberger, SJ and Cui, L and Dharia, N and Winzeler, E and Cui, L}, title = {Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes.}, journal = {BMC genomics}, volume = {10}, number = {}, pages = {610}, pmid = {20015349}, issn = {1471-2164}, support = {1F32AI074242-01A1/AI/NIAID NIH HHS/United States ; AI064553/AI/NIAID NIH HHS/United States ; R01AI059472/AI/NIAID NIH HHS/United States ; }, mesh = {Binding Sites ; *Chromatin Assembly and Disassembly ; Chromatin Immunoprecipitation ; Chromosome Mapping ; DNA, Intergenic/genetics ; DNA, Protozoan/genetics ; *Genome, Protozoan ; Histones/*genetics ; Methylation ; Nucleosomes/*genetics ; Oligonucleotide Array Sequence Analysis ; Plasmodium falciparum/*genetics ; RNA, Messenger/genetics ; Telomere/genetics ; Transcription Factors/genetics ; Transcription Initiation Site ; }, abstract = {BACKGROUND: Epigenetic modifications of histones and regulation of chromatin structure have been implicated in regulation of virulence gene families in P. falciparum. To better understand chromatin-mediated gene regulation, we used a high-density oligonucleotide microarray to map the position and enrichment of nucleosomes across the entire genome of P. falciparum at three time points of the intra-erythrocytic developmental cycle (IDC) in vitro. We used an unmodified histone H4 antibody for chromatin immunoprecipitation of nucleosome-bound DNA.

RESULTS: We observed generally low nucleosomal occupancy of intergenic regions and higher occupancy of protein coding regions. In contract to the overall small fluctuation of nucleosomal occupancy in most coding regions throughout the IDC, subtelomeric genes encoding surface proteins such as var and rif, as well as some core chromosomal genes such as transcription factors, showed large changes in chromatin structure. Telomeres harbored a region with the highest nucleosomal occupancy of the genome and also exhibited large changes with higher nucleosomal occupancy at schizont stages. While many of these subtelomeric genes were previously shown to be modified by H3K9 trimethylation, we also identified some housekeeping genes in core chromosome regions that showed extensive changes in chromatin structure but do not contain this modification. tRNA and basal transcription factor genes showed low nucleosomal occupancy at all times, suggesting of an open chromatin structure that might be permissive for constitutively high levels of expression. Generally, nucleosomal occupancy was not correlated with the steady-state mRNA levels. Several var genes were exceptions: the var gene with the highest expression level showed the lowest nucleosomal occupancy, and selection of parasites for var2CSA expression resulted in lower nucleosomal occupancy at the var2CSA locus. We identified nucleosome-free regions in intergenic regions that may serve as transcription start sites or transcription factor binding sites. Using the nucleosomal occupancy data as the baseline, we further mapped the genome-wide enrichment of H3K9 acetylation and detected general enrichment of this mark in intergenic regions.

CONCLUSIONS: These data on nucleosome enrichment changes add to our understanding of the influence of chromatin structure on the regulation of gene expression. Histones are generally enriched in coding regions, and relatively poor in intergenic regions. Histone enrichment patterns allow for identification of new putative gene-coding regions. Most genes do not show correlation between chromatin structure and steady-state mRNA levels, indicating the dominant roles of other regulatory mechanisms. We present a genome-wide nucleosomal occupancy map, which can be used as a reference for future experiments of histone modification mapping.}, } @article {pmid20013346, year = {2010}, author = {Zhao, J and Lang, R and Guo, X and Chen, L and Gu, F and Fan, Y and Fu, X and Fu, L}, title = {Clinicopathologic characteristics of pleomorphic carcinoma of the breast.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {456}, number = {1}, pages = {31-37}, pmid = {20013346}, issn = {1432-2307}, mesh = {Adult ; Aged ; Anion Exchange Protein 1, Erythrocyte/analysis ; Antiporters/analysis ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Immunohistochemistry ; Membrane Proteins/analysis ; Middle Aged ; Mucin-1/analysis ; Proliferating Cell Nuclear Antigen/analysis ; Proto-Oncogene Proteins c-bcl-2/analysis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Retrospective Studies ; S100 Proteins/analysis ; Tumor Suppressor Protein p53/analysis ; }, abstract = {Pleomorphic carcinoma of the breast is considered a rare variant of high-grade ductal NOS carcinoma (NOS-IDC), and the prognosis is poor. However, its clinicopathologic features are not well-characterized. Using the criteria delineated in the World Health Organization breast tumor classification of 2003, ten cases of pleomorphic carcinoma were identified from 9794 NOS-IDC in our archived materials that were originally diagnosed as high-grade infiltrating ductal carcinoma of breast. To investigate the clinicopathologic characteristics and to elucidate the histologic diagnosis and differential diagnosis of this entity, we reviewed the pathology manifestations and clinical features of these cases and examined the tumor expression of ER, PR, PCNA, AE(1)/AE(3), p53, S-100, C-erbB-2, EMA, p63, and Bcl-2 by immunohistochemistry.}, } @article {pmid20009749, year = {2010}, author = {Ingkakul, T and Sadakari, Y and Ienaga, J and Satoh, N and Takahata, S and Tanaka, M}, title = {Predictors of the presence of concomitant invasive ductal carcinoma in intraductal papillary mucinous neoplasm of the pancreas.}, journal = {Annals of surgery}, volume = {251}, number = {1}, pages = {70-75}, doi = {10.1097/SLA.0b013e3181c5ddc3}, pmid = {20009749}, issn = {1528-1140}, mesh = {Adenocarcinoma, Mucinous/*diagnosis/pathology ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*diagnosis/pathology ; Carcinoma, Papillary/*diagnosis/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis ; Pancreatic Neoplasms/*diagnosis/pathology ; }, abstract = {OBJECTIVE: Invasive ductal carcinoma (DC) of the pancreas arising as an independent lesion in association with intraductal papillary mucinous neoplasm (IPMN) has occasionally been reported. However, clinicopathological features related to the presence of DC in patients with IPMN remain largely unknown. The purpose of the present study was to determine the factors predicting the presence of concomitant DC in those with IPMN.

MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological data of a consecutive series of 236 patients with IPMN treated by surgical resection or followed up at our institution between January 1987 and June 2008. In an attempt to identify predictors for the presence of DC, clinicopathological variables were compared between IPMN patients with concomitant DC and those without concomitant DC.

RESULTS: Of 236 patients with IPMN, concomitant DC was detected synchronously or metachronously in 22 patients (9.3%). All the 22 IPMNs were of branch duct type and histological grades of 12 resected IPMNs were adenoma(n = 8) and borderline (n = 4). Multivariate analysis revealed 2 significant predictive factors for the presence of DC in IPMN, including worsening diabetes mellitus (P < 0.001) and an abnormal serum CA 19-9 level (P = 0.024).

CONCLUSION: In view of the high prevalence of DC careful inspection of the entire pancreatic gland is necessary for early detection of DC in patients with branch duct IPMNs, especially when worsening diabetes mellitus and an abnormal serum CA 19-9 level are manifested.}, } @article {pmid20006543, year = {2010}, author = {Levit-Binnun, N and Litvak, V and Pratt, H and Moses, E and Zaroor, M and Peled, A}, title = {Differences in TMS-evoked responses between schizophrenia patients and healthy controls can be observed without a dedicated EEG system.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {121}, number = {3}, pages = {332-339}, doi = {10.1016/j.clinph.2009.10.035}, pmid = {20006543}, issn = {1872-8952}, mesh = {Adolescent ; Adult ; Algorithms ; Artifacts ; Brain/*physiopathology ; Data Interpretation, Statistical ; Diagnosis, Differential ; Electroencephalography/*methods ; Evoked Potentials/*physiology ; Female ; Humans ; Male ; Predictive Value of Tests ; Reference Values ; Schizophrenia/*diagnosis/*physiopathology ; Sensitivity and Specificity ; Signal Processing, Computer-Assisted ; Transcranial Magnetic Stimulation/*methods ; Young Adult ; }, abstract = {OBJECTIVE: The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been hampered by the large artifact that the TMS generates in the EEG. Using TMS with EEG necessitates a sophisticated artifact-resistant EEG system that can acquire reliable signals in the crucial several tens of milliseconds immediately following the TMS pulse. Here, we demonstrate the use of a novel artifact removal algorithm together with a 24-bit EEG system to achieve similar recordings as those obtained with the dedicated TMS-compatible EEG system.

METHODS: This setup was used to compare TMS-evoked responses between a group of healthy controls and a group of patients with schizophrenia, a condition in which effective neural connectivity is thought to be compromised.

RESULTS: We observe differences in TMS-evoked responses between the two groups, similar to those recently reported in a study that used a dedicated TMS-compatible EEG system.

CONCLUSIONS: The standard 24-bit EEG system combined with an artifact removal algorithm produces results similar to the dedicated TMS-compatible system.

SIGNIFICANCE: This paves the way for more researchers and clinicians to use TMS-evoked responses for research and diagnosis of a wide spectrum of disorders.}, } @article {pmid20005901, year = {2010}, author = {Hodrea, J and Demény, MA and Majai, G and Sarang, Z and Korponay-Szabó, IR and Fésüs, L}, title = {Transglutaminase 2 is expressed and active on the surface of human monocyte-derived dendritic cells and macrophages.}, journal = {Immunology letters}, volume = {130}, number = {1-2}, pages = {74-81}, doi = {10.1016/j.imlet.2009.12.010}, pmid = {20005901}, issn = {1879-0542}, mesh = {Animals ; Dendritic Cells/chemistry/*enzymology/*immunology ; Flow Cytometry ; GTP-Binding Proteins/chemistry/*metabolism ; Humans ; Immunoblotting ; Leukocytes, Mononuclear/*immunology ; Macrophages/chemistry/*enzymology/*immunology ; Membrane Proteins/*metabolism ; Mice ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/chemistry/*metabolism ; }, abstract = {The multifunctional enzyme, transglutaminase 2 (TG2), can be found intracellularly, in the extracellular matrix and on the cell surface. Cell surface TG2 (csTG2) could not be detected by TG2-specific antibodies or autoantibodies on immunocompetent cells. A supposedly csTG2-specific antibody, 6B9, was recently shown to actually react with CD44. Though the importance of TG2-mediated deamidation of gluten in the pathogenesis of celiac disease has been well recognized, it is not known in which intestinal cells or cell compartment the deamidation occurs. Duodenal dendritic cells (DCs) can be directly involved in gluten-reactive T-cell activation. Here we use blood monocyte-derived dendritic cells (iDC) and macrophages (MPhi) as a model for intestinal antigen-presenting cells (APCs) and show that they contain large amounts of TG2. We found that TG100, a commercial TG2-specific monoclonal antibody can recognize TG2 on the surface of these cells, that is monocyte-derived APCs express surface-associated TG2. TG2 expression was found on the surface of individual tunica propria cells in frozen small bowel tissue sections from both normal and celiac subjects. We also demonstrate that the pool of TG2 on the surface of iDCs can be catalytically active, hence it might directly be involved in the deamidation of gliadin peptides. Bacterial lipopolysaccharide (LPS) increased the level of TG2 on the surface of maturing DCs, supporting the hypothesis that an unspecific inflammatory process in the gut may expose more transglutaminase activity.}, } @article {pmid19997809, year = {2009}, author = {Izumi, S and Nakamura, S and Mano, S and Suzuka, I}, title = {Resection of four synchronous invasive ductal carcinomas in the pancreas head and body associated with pancreatic intraepithelial neoplasia: report of a case.}, journal = {Surgery today}, volume = {39}, number = {12}, pages = {1091-1097}, pmid = {19997809}, issn = {1436-2813}, mesh = {Adenocarcinoma/*pathology/surgery ; Aged ; Biopsy, Needle ; Carcinoma in Situ/*pathology/surgery ; Carcinoma, Pancreatic Ductal/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; Neoplasms, Multiple Primary/*pathology/surgery ; Pancreatic Neoplasms/*pathology/surgery ; Pancreaticoduodenectomy/methods ; Risk Assessment ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, abstract = {This report describes a very rare case of four synchronous invasive ductal carcinomas (IDCs) in the pancreas head and body with possible multicentricity. The patient was a 75-year-old woman. Abdominal dynamic computed tomography showed four low-density masses (25 mm, 20 mm, 10 mm, and 10 mm in diameter) in the pancreas head and body. The patient underwent a pylorus-preserving subtotal pancreatoduodenectomy. Histologically, the discontinuity between the four tumors was confirmed; one tumor (20 mm) was moderately differentiated tubular adenocarcinoma, and the others (25 mm, 10 mm, and 10 mm) were papillary adenocarcinomas. Two smaller papillary adenocarcinomas were composed of abundant fibrosis, pancreatic intraepithelial neoplasia (PanIN) 2-3, and IDC with stromal invasion. PanIN-1-2 lesions proximal to the four IDCs were evident. The immunohistochemical staining by CK20, MUC1, and Ki-67 revealed apparently different features for 2 IDCs (25 mm and 20 mm) and somewhat differential features for three papillary adenocarcinomas. Therefore, the progression of PanIN to IDC and multicentric occurrences of these four IDCs were possible. In this report, we show that immunohistochemistry and the confirmation of the presence of PanINs in IDC were useful to some extent for the study of multiple pancreatic cancers.}, } @article {pmid19995377, year = {2009}, author = {Moran, MS and Yang, Q and Haffty, BG}, title = {The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology.}, journal = {The breast journal}, volume = {15}, number = {6}, pages = {571-578}, doi = {10.1111/j.1524-4741.2009.00833.x}, pmid = {19995377}, issn = {1524-4741}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/pathology/*surgery ; Carcinoma, Ductal, Breast/chemistry/pathology/*surgery ; Carcinoma, Lobular/chemistry/pathology/*surgery ; Cyclooxygenase 2/*analysis ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Treatment Outcome ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {To evaluate our experience of the clinical-pathologic features and outcomes of early-stage Invasive Lobular (ILC) versus Invasive Ductal (IDC) carcinoma treated with breast conservation treatment (BCT). 142 ILC and 1,760 IDC patients were treated with BCT at our institution. All patients underwent breast conserving surgery and radiation therapy (median total dose: 64 Gy). Clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. In addition, COX-2, Bcl-2, and p-53 expression was analyzed from our existing tissue micro-array database. Median follow-up was 6.8 years. A higher percentage of ILC patients presented at >40 years of age (94% ILC versus 89% IDC, p = 0.0353) and had more mammographically occult tumors (p < 0.002). There were no significant differences in T stage, nodal status, family history, final margin, ER/PR/HER-2 status or triple negative tumors (all p-values >0.05). From the immuno-histochemical analysis, expression of p53, COX-2, and Bcl-2 did not differ significantly (all p-values >0.05) between the two cohorts. At 10 years, there was no difference in breast relapse (20% versus 13%, p = 0.25), distant relapse (26% versus 20%, p = 0.28), cause-specific survival (72% versus 84%, p = 0.09) and OS (68% versus 78%, p = 0.08). Patients with ILC had higher contralateral breast relapses (26% versus 12%, p = 0.0006). Patients with early-stage ILC have comparable outcomes to IDC when treated with BCT. Because of the higher risk of contralateral breast cancers for ILC patients, careful evaluation of the contralateral breast will be important in the follow-up of these patients. Future investigations of chemo-preventive strategies to decrease contralateral breast cancers are warranted.}, } @article {pmid19968660, year = {2010}, author = {Peiró, G and Adrover, E and Guijarro, J and Ballester, I and Jimenez, MJ and Planelles, M and Catasús, L}, title = {Synchronous bilateral breast carcinoma in a patient with cowden syndrome: a case report with morphologic, immunohistochemical and genetic analysis.}, journal = {The breast journal}, volume = {16}, number = {1}, pages = {77-81}, doi = {10.1111/j.1524-4741.2009.00846.x}, pmid = {19968660}, issn = {1524-4741}, mesh = {Adult ; Axilla ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*pathology/surgery ; Breast Self-Examination ; Carcinoma, Ductal, Breast/drug therapy/genetics/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Genetic Testing ; Hamartoma Syndrome, Multiple/*diagnosis ; Humans ; Immunohistochemistry ; Lymph Node Excision/*methods ; Lymph Nodes/pathology/surgery ; Magnetic Resonance Imaging ; Mammography/methods ; Mastectomy/*methods ; Neoplasm Staging ; Neoplasms, Multiple Primary/drug therapy/*pathology/surgery ; Treatment Outcome ; }, abstract = {Synchronous bilateral breast carcinoma (SBBC) and early onset are important characteristics of hereditary cases. The lifetime risk for breast carcinoma in Cowden syndrome (CS) is estimated to be 25-50%. We reported a 44-year-old woman presenting SBBC and characteristic mucocutaneous lesions of CS, confirmed by PTEN gene mutation analysis. Bilateral modified mastectomy and axillary dissection were performed. Histopathologic examination revealed a moderate-differentiated invasive ductal carcinoma with mixed features of luminal A immunophenotype (Estrogen and/or Progesterone Receptors >50% and/or Ki67 < 30% of positive cells). The skin lesions showed the characteristic findings of tricholemmoma. Lack of PTEN expression was observed in all specimens. Sequencing analysis confirmed the presence of PTEN splice-acceptor site mutation in intron 8 (c.1027-2A>G), a germline mutation which had not been previously reported in CS. The patient received adjuvant chemotherapy and tamoxifen for 5 years. After 5 years of follow-up, she persists recurrence-free. SBBC with early onset suggests a hereditary predisposition. Thus, analysis of PTEN expression abnormality, easily assessed by immunohistochemistry, may be of clinical value to screen those patients with CS.}, } @article {pmid19967723, year = {2010}, author = {Germain, M and De Arcangelis, A and Robinson, SD and Baker, M and Tavora, B and D'Amico, G and Silva, R and Kostourou, V and Reynolds, LE and Watson, A and Jones, JL and Georges-Labouesse, E and Hodivala-Dilke, K}, title = {Genetic ablation of the alpha 6-integrin subunit in Tie1Cre mice enhances tumour angiogenesis.}, journal = {The Journal of pathology}, volume = {220}, number = {3}, pages = {370-381}, doi = {10.1002/path.2654}, pmid = {19967723}, issn = {1096-9896}, support = {12007/CRUK_/Cancer Research UK/United Kingdom ; 2003:602/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Animals ; Breast Neoplasms/*blood supply/metabolism ; Carcinoma, Ductal, Breast/blood supply ; Carcinoma, Lewis Lung/blood supply/metabolism/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Genotype ; Humans ; Integrin alpha6/*genetics/metabolism/physiology ; Melanoma/blood supply/metabolism/pathology ; Mice ; Mice, Knockout ; Neoplasm Proteins/*genetics/metabolism/physiology ; Neoplasm Transplantation ; Neoplasms, Experimental/*blood supply/metabolism ; Neovascularization, Pathologic/chemically induced/*genetics/metabolism ; Polymerase Chain Reaction/methods ; Vascular Endothelial Growth Factor A/toxicity ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; }, abstract = {Laminins are expressed highly in blood vessel basement membranes and have been implicated in angiogenesis. alpha6beta1- and alpha6beta4-integrins are major receptors for laminins in endothelial cells, but the precise role of endothelial alpha6-integrin in tumour angiogenesis is not clear. We show that blood vessels in human invasive ductal carcinoma of the breast have decreased expression of the alpha6-integrin-subunit when compared with normal breast tissue. These data suggest that a decrease in alpha6-integrin-subunit expression in endothelial cells is associated with tumour angiogenesis. To test whether the loss of the endothelial alpha6-integrin subunit affects tumour growth and angiogenesis, we generated alpha6fl/fl-Tie1Cre+ mice and showed that endothelial deletion of alpha6-integrin is sufficient to enhance tumour size and tumour angiogenesis in both murine B16F0 melanoma and Lewis cell lung carcinoma. Mechanistically, endothelial alpha6-integrin deficiency elevated significantly VEGF-mediated angiogenesis both in vivo and ex vivo. In particular, alpha6-integrin-deficient endothelial cells displayed increased levels of VEGF-receptor 2 (VEGFR2) and VEGF-mediated downstream ERK1/2 activation. By developing the first endothelial-specific alpha6-knockout mice, we show that the expression of the alpha6-integrin subunit in endothelial cells acts as a negative regulator of angiogenesis both in vivo and ex vivo.}, } @article {pmid19964024, year = {2009}, author = {Hall, TJ and Oberait, AA and Barbone, PE and Sommer, AM and Gokhale, NH and Goenezent, S and Jiang, J}, title = {Elastic nonlinearity imaging.}, journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference}, volume = {2009}, number = {}, pages = {1967-1970}, doi = {10.1109/IEMBS.2009.5333442}, pmid = {19964024}, issn = {2375-7477}, support = {R01CA100373/CA/NCI NIH HHS/United States ; R21CA133488/CA/NCI NIH HHS/United States ; }, mesh = {Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal/diagnostic imaging ; Elastic Modulus ; Elasticity ; Elasticity Imaging Techniques/*methods ; Female ; Fibroadenoma/diagnostic imaging ; Humans ; Image Enhancement/methods ; Image Processing, Computer-Assisted/methods ; Neoplasm Invasiveness/diagnostic imaging ; Nonlinear Dynamics ; Prognosis ; Sprains and Strains/physiopathology ; Stress, Mechanical ; }, abstract = {Previous work has demonstrated improved diagnostic performance of highly trained breast radiologists when provided with B-mode plus elastography images over B-mode images alone. In those studies we have observed that elasticity imaging can be difficult to perform if there is substantial motion of tissue out of the image plane. So we are extending our methods to 3D/4D elasticity imaging with 2D arrays. Further, we have also documented the fact that some breast tumors change contrast with increasing deformation and those observations are consistent with in vitro tissue measurements. Hence, we are investigating imaging tissue stress-strain nonlinearity. These studies will require relatively large tissue deformations (e.g., > 20%) which will induce out of plane motion further justifying 3D/4D motion tracking. To further enhance our efforts, we have begun testing the ability to perform modulus reconstructions (absolute elastic parameter) imaging of in vivo breast tissues. The reconstructions are based on high quality 2D displacement estimates from strain imaging. Piecewise linear (secant) modulus reconstructions demonstrate the changes in elasticity image contrast seen in strain images but, unlike the strain images, the contrast in the modulus images approximates the absolute modulus contrast. Nonlinear reconstructions assume a reasonable approximation to the underlying constitutive relations for the tissue and provide images of the (near) zero-strain shear modulus and a nonlinearity parameter that describes the rate of tissue stiffening with increased deformation. Limited data from clinical trials are consistent with in vitro measurements of elastic properties of tissue samples and suggest that the nonlinearity of invasive ductal carcinoma exceeds that of fibroadenoma and might be useful for improving diagnostic specificity. This work is being extended to 3D.}, } @article {pmid19954911, year = {2010}, author = {Baltzer, PA and Kaiser, CG and Dietzel, M and Vag, T and Herzog, AB and Gajda, M and Camara, O and Kaiser, WA}, title = {Value of ductal obstruction sign in the differentiation of benign and malignant breast lesions at MR imaging.}, journal = {European journal of radiology}, volume = {75}, number = {2}, pages = {e18-21}, doi = {10.1016/j.ejrad.2009.10.032}, pmid = {19954911}, issn = {1872-7727}, mesh = {Adolescent ; Adult ; Aged, 80 and over ; Breast/pathology ; Breast Diseases/diagnosis ; Breast Neoplasms/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammary Glands, Human/*pathology ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Young Adult ; }, abstract = {PURPOSE: MR-Mammography (MRM) is regarded as the most sensitive method for detection of breast cancer without a broad consensus on specificity. There is room for improvement of the existing ACR BIRADS lexicon by adding new and specific descriptors. Dilated ducts have been described in association with papillomas. However, the differential diagnostic value of this finding has not been investigated yet.

MATERIALS AND METHODS: 316 consecutive patients, undergoing histopathologic workup after MR-Mammography were included in this prospective, ethical review board approved study. Two blinded radiologists rated the images in consensus. Ductal obstruction was defined as dilated liquid filled ducts proximal an enhancing lesion. Sensitivity, specificity as well as positive and negative likelihood ratio (LR+, LR-) were calculated.

RESULTS: Dilated ducts were found in 60 cases (19%), 20 of these showed an association with enhancing lesions and were categorized as ductal obstruction (6.3%). Malignancy was found in two cases (one invasive ductal carcinoma and one DCIS) and benign tissue in 18 cases (15 papillomas). The difference of ductal obstruction between these groups was found to be highly significant in two-sided Fisher's exact test (p<0.001). Because of the clear association with benign lesions, benign lesions showing ductal obstruction were characterized as true positive findings. Therefore, following diagnostic parameters were calculated: sensitivity 15.4%, specificity 99.0%, LR+ 15.3, LR- 0.9.

DISCUSSION: If ductal obstruction is found to be positive, the associated lesion is most likely benign. Therefore, though a rare finding, this descriptor should be taken into account for improved lesion differentiation.}, } @article {pmid19949854, year = {2010}, author = {Sharma, M and Beck, AH and Webster, JA and Espinosa, I and Montgomery, K and Varma, S and van de Rijn, M and Jensen, KC and West, RB}, title = {Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ.}, journal = {Breast cancer research and treatment}, volume = {123}, number = {2}, pages = {397-404}, pmid = {19949854}, issn = {1573-7217}, support = {R01 CA129927/CA/NCI NIH HHS/United States ; R01 CA129927-01A2/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/*genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/*genetics/pathology ; Disease Progression ; Female ; Fibroblasts/chemistry ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Genotype ; Humans ; Immunohistochemistry ; Macrophages/chemistry ; Neoplasm Invasiveness ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Stromal Cells/*chemistry/pathology ; Tissue Array Analysis ; }, abstract = {Recent advances in the study of the tumor microenvironment have revealed significant interaction between tumor cells and their surrounding stroma in model systems. We have previously shown that two distinct stromal signatures derived from a macrophage (CSF1) response and a fibroblastic (DTF-like) response are present in subsets of invasive breast cancers and show a correlation with clinical outcome. In the present study we explore whether these signatures also exist in the stroma of ductal carcinoma in situ (DCIS). We studied the signatures by both gene expression profile analysis of a publically available data set of DCIS and by immunohistochemistry (IHC) on a tissue microarray of DCIS and invasive breast cancer cases. Both the gene expression and immunohistochemical data show that the macrophage response and fibroblast expression signatures are present in the stroma of subsets of DCIS cases. The incidence of the stromal signatures in DCIS is similar to the incidence in invasive breast cancer that we have previously reported. We also find that the macrophage response signature is associated with higher grade DCIS and cases which are ER and PR negative, whereas the fibroblast signature was not associated with any clinicopathologic features in DCIS. A comparison of 115 matched cases of DCIS and invasive breast cancer found a correlation between the type of stromal response in DCIS and invasive ductal carcinoma (IDC) within the same patient for both the macrophage response and the fibroblast stromal signatures (P = 0.03 and 0.08, respectively). This study is a first characterization of these signatures in DCIS. These signatures have significant clinicopathologic associations and tend to be conserved as the tumor progresses from DCIS to invasive breast cancer.}, } @article {pmid19946485, year = {2009}, author = {Gashi-Luci, LH and Limani, RA and Kurshumliu, FI}, title = {Invasive ductal carcinoma within fibroadenoma: a case report.}, journal = {Cases journal}, volume = {2}, number = {}, pages = {174}, pmid = {19946485}, issn = {1757-1626}, abstract = {INTRODUCTION: Fibroadenoma is the most common benign tumor of the female breast with the highest incidence before age 30. Fibroadenoma may be associated with fibrocystic changes, proliferative epithelial changes, and extremely rarely, with non-invasive and invasive cancer.

CASE PRESENTATION: We present a rare case of a 39 years old female with invasive ductal carcinoma arising within fibroadenoma.

CONCLUSION: There is a low percentage of fibroadenomas harboring carcinoma; however, all breast lumps should be seriously managed; extirpation and histological examination is recommended.}, } @article {pmid19945859, year = {2011}, author = {Elliott, RL and DeLand, M and Head, JF and Elliott, MC}, title = {Accelerated partial breast irradiation: initial experience with the Intrabeam System.}, journal = {Surgical oncology}, volume = {20}, number = {2}, pages = {73-79}, doi = {10.1016/j.suronc.2009.11.001}, pmid = {19945859}, issn = {1879-3320}, mesh = {*Brachytherapy ; Breast Neoplasms/pathology/*radiotherapy ; Female ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; }, abstract = {Failure after breast conserving surgery (BCS) and total breast irradiation usually occurs at the site of the original tumor. This has caused an increased interest in accelerated partial breast irradiation (APBI), because if radiation is delivered directly to the tumor bed there should be better local control. Patients greater than age 50 with core biopsy confirmed invasive ductal carcinoma were enrolled. They had preoperative ultrasound defining margins of less than 3.5 cm. Intraoperative ultrasound was also performed in an effort to ensure good surgical margins. After excision of the tumor, intraoperative radiotherapy (IORT) with the Intrabeam System was delivered to the tumor bed. The procedure has been performed on 67 patients. Sixty-one patients had it with the original surgery, while 6 had the procedure after re-exploration of the segmental mastectomy site. Because of the final pathology (surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomy and 11 received total breast irradiation. When total breast irradiation is done the IORT serves as the radiation boost. The cosmetic results have been good to excellent, and there have been no serious surgical or radiation complications. To date there have been no local failures. IORT with the Intrabeam System is feasible, user friendly, versatile, with few complications, good cosmetic results, and great patient acceptance. It is practical and excellent for breast IORT in the community setting.}, } @article {pmid19945801, year = {2010}, author = {Safali, M and Karslioğlu, Y and Arpaci, F and Kurt, B and Günhan, O}, title = {A distinct microvascular pattern accompanied by aggressive clinical course in breast carcinomas: a fact or a coincidence?.}, journal = {Pathology, research and practice}, volume = {206}, number = {2}, pages = {93-97}, doi = {10.1016/j.prp.2009.10.004}, pmid = {19945801}, issn = {1618-0631}, mesh = {Adult ; Aged ; Antigens, CD34/biosynthesis ; Breast Neoplasms/*blood supply/mortality/*pathology ; Carcinoma, Ductal, Breast/*blood supply/mortality/*pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/metabolism/pathology ; Prognosis ; }, abstract = {The aim of this study was to evaluate the potential relationship of microvascular growth patterns with survival in invasive breast carcinomas. Thirty-one invasive ductal carcinoma cases, followed up at least for 38 months, constituted our series. All cases had been studied for ER/PR and HER2/neu expression. Clinicopathological and survival data were obtained from the archives. Tissue sections from all cases were stained with CD34 antibody to highlight the microvascular network and to measure microvessel density (MVD). The cases were then classified according to the dominance of one of the five recognizable microvascular patterns. Cox proportional hazard regression model, Fisher's exact test, and multivariate general linear model (GLM) were used to uncover the effects of the variables, such as nodal status, distant metastasis, angiogenic patterns, and MVD, on survival. There was an association between only one of the microvascular patterns and aggressive clinical course. Increased blood-filled capillaries with some clustering in the tumor might be a predictor of aggressive biological behavior in invasive breast carcinomas. Similar studies investigating larger series are needed before a generalized conclusion can be made.}, } @article {pmid19944674, year = {2010}, author = {Prasad, CP and Rath, G and Mathur, S and Bhatnagar, D and Ralhan, R}, title = {Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines.}, journal = {Chemico-biological interactions}, volume = {183}, number = {3}, pages = {455-461}, doi = {10.1016/j.cbi.2009.11.019}, pmid = {19944674}, issn = {1872-7786}, mesh = {Antineoplastic Agents/*pharmacology ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Curcumin/*pharmacology ; Female ; Humans ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Serpins/genetics/*metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation ; }, abstract = {In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.}, } @article {pmid19944605, year = {2010}, author = {Gentilini, O and Botteri, E and Rotmensz, N and Toesca, A and De Oliveira, H and Sangalli, C and Colleoni, M and Intra, M and Galimberti, V and Veronesi, P and Luini, A and Veronesi, U}, title = {Breast-conserving surgery in 201 very young patients (<35 years).}, journal = {Breast (Edinburgh, Scotland)}, volume = {19}, number = {1}, pages = {55-58}, doi = {10.1016/j.breast.2009.11.001}, pmid = {19944605}, issn = {1532-3080}, mesh = {Adult ; Age Factors ; Breast Neoplasms/*epidemiology/mortality/*surgery ; Disease-Free Survival ; Female ; Humans ; Italy/epidemiology ; Mastectomy, Segmental/*statistics & numerical data ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Sentinel Lymph Node Biopsy/statistics & numerical data ; Treatment Outcome ; Women's Health ; Young Adult ; }, abstract = {INTRODUCTION: Surgical treatment of breast cancer in very young patients (<35 years) is still a matter of debate, since age is a predictive factor of local recurrence after breast conservation.

PATIENTS AND METHODS: We retrospectively evaluated outcome and prognostic factors of 201 consecutive patients treated with breast conservation followed by whole breast irradiation between 1997 and 2004 with special attention paid to local control. The average follow up was 72 months (range 13-133 months).

RESULTS: The mean age was 32 years (Range 20-34). Invasive ductal carcinoma was found in 175 (87.1%) patients. Two (1%) patients had invasive lobular carcinoma. One-hundred and eighteen patients (58.7%) had tumors of 2 cm or smaller. Sentinel lymph node biopsy was performed in 105 (52.2%) patients. One-hundred and ten (54.7%) patients had node-negative disease, 68 (33.8%) patients had 1-3 positive nodes and 23 (11.4%) +4 positive nodes. Eighteen patients (9.0%) developed a local recurrence, 25 (12.5%) developed distant metastases and 23 patients (11.4%) died during follow up. The 5- and 10-year cumulative incidence of local events were 8.2% and 12,3% respectively. The univariate analysis did not identify any variables affecting local disease-free survival.

CONCLUSIONS: Breast conservation in very young patients achieves an acceptable local control rate. No prognostic factors were associated with local events.}, } @article {pmid19932795, year = {2009}, author = {Dimas, VV and Denfield, SW and Friedman, RA and Cannon, BC and Kim, JJ and Smith, EO and Clunie, SK and Price, JF and Towbin, JA and Dreyer, WJ and Kertesz, NJ}, title = {Frequency of cardiac death in children with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {104}, number = {11}, pages = {1574-1577}, doi = {10.1016/j.amjcard.2009.07.034}, pmid = {19932795}, issn = {1879-1913}, mesh = {Adolescent ; Arrhythmias, Cardiac/mortality ; Cardiomyopathy, Dilated/diagnosis/epidemiology/*mortality ; Child ; Child, Preschool ; Death, Sudden, Cardiac/*epidemiology/prevention & control ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Medical Records ; Prognosis ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Texas/epidemiology ; }, abstract = {The prognosis in children with idiopathic dilated cardiomyopathy (IDC) is guarded, with the 5-year mortality rate ranging from 14% to 50%, owing to sudden cardiac death (SCD) or pump failure. The risk factors for SCD in adults with IDC include asymptomatic nonsustained ventricular tachycardia and poor left ventricular function. It is unclear whether these findings can be extrapolated to the pediatric population. A retrospective review of all patients with the diagnosis of IDC seen at a single institution from 1990 to 2004 was performed. A total of 85 patients (46 males), with a median age of 3.8 years (0 days to 17.3 years) were studied. The mean left ventricular ejection fraction was 25 +/- 12% (median 23%, range 45% to 45%) at presentation. The following arrhythmias occurred at presentation or during the initial hospitalization: nonsustained ventricular tachycardia in 6, sustained ventricular tachycardia or fibrillation in 1, supraventricular arrhythmias in 6, and both atrial and ventricular arrhythmias in 1. During a subsequent hospitalization or outpatient follow-up, 7 patients had the following arrhythmias: supraventricular arrhythmias in 2, nonsustained ventricular tachycardia in 4, and both atrial and ventricular arrhythmias in 1. The cumulative survival rate was 40% at a mean follow-up of 6.2 years (95% confidence interval 4.4 to 8.1). One single episode of SCD occurred in 1 patient without a history of sustained arrhythmias. In conclusion, in children with IDC, despite the low left ventricular ejection fraction and presence of ventricular arrhythmias, only one episode of SCD occurred in this group of patients. Given the 1% incidence of SCD in this cohort, the use of implantable cardioverter-defibrillators as primary prevention in children with IDC might not be indicated.}, } @article {pmid19932096, year = {2010}, author = {García-Becerra, R and Díaz, L and Camacho, J and Barrera, D and Ordaz-Rosado, D and Morales, A and Ortiz, CS and Avila, E and Bargallo, E and Arrecillas, M and Halhali, A and Larrea, F}, title = {Calcitriol inhibits Ether-à go-go potassium channel expression and cell proliferation in human breast cancer cells.}, journal = {Experimental cell research}, volume = {316}, number = {3}, pages = {433-442}, doi = {10.1016/j.yexcr.2009.11.008}, pmid = {19932096}, issn = {1090-2422}, mesh = {Adult ; Aged ; Blotting, Western ; Breast Neoplasms/genetics/*metabolism/*pathology ; Calcitriol/*pharmacology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Ether-A-Go-Go Potassium Channels/*antagonists & inhibitors/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Middle Aged ; Receptors, Calcitriol/metabolism ; }, abstract = {Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-à-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.}, } @article {pmid19922592, year = {2009}, author = {Geyer, FC and Kushner, YB and Lambros, MB and Natrajan, R and Mackay, A and Tamber, N and Fenwick, K and Purnell, D and Ashworth, A and Walker, RA and Reis-Filho, JS}, title = {Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma.}, journal = {Histopathology}, volume = {55}, number = {6}, pages = {732-743}, doi = {10.1111/j.1365-2559.2009.03432.x}, pmid = {19922592}, issn = {1365-2559}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Adenoma/*diagnosis/*genetics ; Aged ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*diagnosis/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/*diagnosis/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Oligonucleotide Array Sequence Analysis ; }, abstract = {AIMS: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non-obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER-2 overexpression (triple-negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC-NST).

METHODS AND RESULTS: We report on a case comprising MGA, AMGA and a high-grade IDC-NST. The three components were separately microdissected and subjected to genetic analysis with high-resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple-negative phenotype and variable positivity for basal markers.

CONCLUSIONS: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non-obligate precursor of a subgroup of high-grade triple-negative and basal-like breast carcinomas.}, } @article {pmid19916181, year = {2009}, author = {Sakamoto, H and Kitano, M and Komaki, T and Imai, H and Kamata, K and Kimura, M and Takeyama, Y and Kudo, M}, title = {Small invasive ductal carcinoma of the pancreas distinct from branch duct intraductal papillary mucinous neoplasm.}, journal = {World journal of gastroenterology}, volume = {15}, number = {43}, pages = {5489-5492}, pmid = {19916181}, issn = {2219-2840}, mesh = {Adenocarcinoma/classification/diagnosis ; Adenocarcinoma, Mucinous/classification/diagnosis ; Aged ; Carcinoma, Pancreatic Ductal/classification/*diagnosis ; Endosonography/*methods ; Female ; Gastroenterology/methods ; Humans ; Medical Oncology/methods ; Neoplasm Invasiveness ; Neoplasms, Second Primary/classification/diagnosis ; Pancreatic Neoplasms/classification/*diagnosis ; Treatment Outcome ; }, abstract = {Endoscopic ultrasonography (EUS) is a highly sensitive diagnostic method for the detection of small pancreatic carcinomas. Recently, there have been some reports describing the utility of contrast-enhanced harmonic EUS (CEH-EUS) which uses sonographic contrast agent for differentiation of a pancreatic mass. This report describes a case of small adenocarcinoma of the pancreas distinct from branch duct intraductal papillary mucinous neoplasm (IPMN) in which investigation by EUS took place every 6 mo and diagnosis was made accurately by additional CEH-EUS during the follow-up of the branch duct IPMN. A 68-year-old female was admitted to our hospital because of a branch duct IPMN in the pancreatic body. She had been followed-up by EUS every 6 mo. However, after 2 years EUS demonstrated a low echoic area distinct from the branch duct IPMN which was vaguely discernible by EUS, and accurate sizing and differential diagnosis were considered difficult on the EUS imaging. CH-EUS with Sonazoid revealed a hypovascular tumor and we suspected small pancreatic carcinoma. The histopathological diagnosis was adenocarcinoma (10 mm) in the pancreatic tail, distinct from the branch duct IPMN of the pancreatic body. EUS and CEH-EUS may play an important role in the correct diagnosis of small pancreatic tumors, including synchronous and metachronous occurrence of IPMN and ductal adenocarcinoma of the pancreas.}, } @article {pmid19915892, year = {2010}, author = {Chang, RK and Chen, AY}, title = {Impact of palivizumab on RSV hospitalizations for children with hemodynamically significant congenital heart disease.}, journal = {Pediatric cardiology}, volume = {31}, number = {1}, pages = {90-95}, pmid = {19915892}, issn = {1432-1971}, mesh = {Antibodies, Monoclonal/economics/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antiviral Agents/economics/*therapeutic use ; Bronchiolitis/epidemiology/*prevention & control/virology ; California/epidemiology ; Case-Control Studies ; Chemoprevention ; Cost-Benefit Analysis ; Drug Costs ; Heart Defects, Congenital/*virology ; Hospitalization/statistics & numerical data ; Humans ; Incidence ; Infant ; Infant, Newborn ; Palivizumab ; Respiratory Syncytial Virus Infections/epidemiology/*prevention & control ; }, abstract = {The objective of this study was to evaluate the impact of palivizumab prophylaxis on respiratory syncytial virus (RSV) hospitalizations among children with hemodynamically significant congenital heart disease (CHD). In 2003, the American Academy of Pediatrics (AAP) revised the bronchiolitis policy statement and recommended the use of palivizumab in children <24 months old with hemodynamically significant CHD (HS-CHD). California statewide hospital discharge data from years 2000-2002 (pre-AAP policy revision) were compared to those from years 2004-2006 (post-AAP policy revision). Hospitalizations due to RSV bronchiolitis for children <2 years of age were identified by IDC-9 CM codes 4661.1, 480.1, and 079.6 as the Principal Diagnosis. Children with CHD and children with HS-CHD were identified by the codiagnoses. The overall RSV hospitalization rate was 71 per 10,000 children <2 years of age. Of all RSV hospitalizations, 3.0% were among children with CHD, and 0.50% among children with HS-CHD. HS-CHD patients accounted for 0.56% of RSV hospitalizations in 2000-2002, compared to 0.46% RSV hospitalizations in 2004-2006. That represents a 19% reduction in RSV hospitalizations among HS-CHD patients after 2003. The 19% decrease in RSV hospitalizations equates to seven fewer hospitalizations (76 hospital days) per year among HS-CHD patients. We conclude that, since the recommendation of palivizumab for children with HS-CHD in 2003, the impact on RSV hospitalizations in California among HS-CHD patients has been limited. Considering the high cost of palivizumab administration, the cost-benefit of RSV prophylaxis with palivizumab warrants further investigation.}, } @article {pmid19914891, year = {2009}, author = {Valencia, JF and Vallverdú, M and Schroeder, R and Voss, A and Vázquez, R and Bayés de Luna, A and Caminal, P}, title = {Complexity of the short-term heart-rate variability.}, journal = {IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society}, volume = {28}, number = {6}, pages = {72-78}, doi = {10.1109/MEMB.2009.934621}, pmid = {19914891}, issn = {1937-4186}, mesh = {Aged ; Algorithms ; Cardiomyopathy, Dilated/diagnosis/*physiopathology ; Death, Sudden, Cardiac/prevention & control ; Entropy ; Heart Rate/*physiology ; Humans ; Linear Models ; Male ; Middle Aged ; Nonlinear Dynamics ; Predictive Value of Tests ; Prognosis ; Risk Assessment/methods ; Sensitivity and Specificity ; *Signal Processing, Computer-Assisted ; Statistics, Nonparametric ; }, abstract = {This work has proposed a methodology based on the concept of entropy rates to study the complexity of the short-term heart-rate variability (HRV) for improving risk stratification to predict sudden cardiac death (SCD) of patients with established ischemic-dilated cardiomyopathy (IDC). The short-term HRV was analyzed during daytime and nighttime by means of RR series. An entropy rate was calculated on the RR series, previously transformed to symbol sequences by means of an alphabet. A statistical analysis permitted to stratify high- and low-risk patients of suffering SCD, with a specificity (SP) of 95% and sensitivity (SE) of 83.3%.}, } @article {pmid19910836, year = {2010}, author = {Fujita, T and Nakagohri, T and Gotohda, N and Takahashi, S and Konishi, M and Kojima, M and Kinoshita, T}, title = {Evaluation of the prognostic factors and significance of lymph node status in invasive ductal carcinoma of the body or tail of the pancreas.}, journal = {Pancreas}, volume = {39}, number = {1}, pages = {e48-54}, doi = {10.1097/MPA.0b013e3181bd5cfa}, pmid = {19910836}, issn = {1536-4828}, mesh = {Carcinoma, Pancreatic Ductal/*pathology/surgery ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Pancreas/pathology/surgery ; Pancreatectomy/statistics & numerical data ; Pancreatic Neoplasms/*pathology/surgery ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: We evaluated prognostic indicators for distal pancreatectomy with regional lymph node dissection in pancreatic body or tail carcinoma.

METHODS: Between 1993 and 2008, 50 patients with ductal carcinoma of the body or tail of the pancreas who underwent distal pancreatectomy with regional lymph node dissection were retrospectively analyzed. Clinicopathological factors associated with patient survival were evaluated.

RESULTS: No in-hospital deaths occurred among the study patients. The overall 5-year survival rate was 19.3%, and median survival was 22.6 months. Univariate analysis revealed that lymph node metastasis, intrapancreatic neural infiltration, peripancreatic nerve plexus infiltration, and tumor differentiation affected patient survival significantly. Multivariate analysis validated lymph node metastasis as an independent prognostic factor. Moreover, the lymph nodes attached to the pancreas were the most frequent metastatic nodes, and the number of metastasis in the lymph nodes attached to the pancreas was significantly associated with survival after surgical resection.

CONCLUSIONS: Lymph node metastasis was a significant and independent prognostic factor for the surgically resected pancreatic body or tail carcinoma. Furthermore, the lymph nodes attached to the pancreas were the most frequent metastatic nodes, and these lymph nodes were potential indicators predicting both tumor extension and survival after surgery for pancreatic body or tail carcinoma.}, } @article {pmid19906927, year = {2010}, author = {Kather, A and Raftery, MJ and Devi-Rao, G and Lippmann, J and Giese, T and Sandri-Goldin, RM and Schönrich, G}, title = {Herpes simplex virus type 1 (HSV-1)-induced apoptosis in human dendritic cells as a result of downregulation of cellular FLICE-inhibitory protein and reduced expression of HSV-1 antiapoptotic latency-associated transcript sequences.}, journal = {Journal of virology}, volume = {84}, number = {2}, pages = {1034-1046}, pmid = {19906927}, issn = {1098-5514}, support = {R37 AI021515/AI/NIAID NIH HHS/United States ; }, mesh = {Apoptosis/*physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism ; Cell Line ; *Dendritic Cells/cytology/physiology/virology ; *Down-Regulation ; Herpesvirus 1, Human/genetics/*pathogenicity/physiology ; Humans ; MicroRNAs/*metabolism ; Virus Latency ; }, abstract = {Herpes simplex virus type 1 (HSV-1) is one of the most frequent and successful human pathogens. It targets immature dendritic cells (iDCs) to interfere with the antiviral immune response. The mechanisms underlying apoptosis of HSV-1-infected iDCs are not fully understood. Previously, we have shown that HSV-1-induced apoptosis of iDCs is associated with downregulation of the cellular FLICE-inhibitory protein (c-FLIP), a potent inhibitor of caspase-8-mediated apoptosis. In this study, we prove that HSV-1 induces degradation of c-FLIP in a proteasome-independent manner. In addition, by using c-FLIP-specific small interfering RNA (siRNA) we show for the first time that downregulation of c-FLIP expression is sufficient to drive uninfected iDCs into apoptosis, underlining the importance of this molecule for iDC survival. Surprisingly, we also observed virus-induced c-FLIP downregulation in epithelial cells and many other cell types that do not undergo apoptosis after HSV-1 infection. Microarray analyses revealed that HSV-1-encoded latency-associated transcript (LAT) sequences, which can substitute for c-FLIP as an inhibitor of caspase-8-mediated apoptosis, are much less abundant in iDCs as compared to epithelial cells. Finally, iDCs infected with an HSV-1 LAT knockout mutant showed increased apoptosis when compared to iDCs infected with the corresponding wild-type HSV-1. Taken together, our results demonstrate that apoptosis of HSV-1-infected iDCs requires both c-FLIP downregulation and diminished expression of viral LAT.}, } @article {pmid19900584, year = {2010}, author = {Noori, S and Hassan, ZM and Taghikhani, M and Rezaei, B and Habibi, Z}, title = {Dihydroartemisinin can inhibit calmodulin, calmodulin-dependent phosphodiesterase activity and stimulate cellular immune responses.}, journal = {International immunopharmacology}, volume = {10}, number = {2}, pages = {213-217}, doi = {10.1016/j.intimp.2009.11.002}, pmid = {19900584}, issn = {1878-1705}, mesh = {Animals ; Antineoplastic Agents/adverse effects/*pharmacology ; Artemisinins/adverse effects/*pharmacology ; Calmodulin/*antagonists & inhibitors ; Carcinoma, Ductal/*metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 1/*antagonists & inhibitors ; Erythrocytes/immunology ; Female ; Hypersensitivity, Delayed/chemically induced/immunology ; Immunity, Cellular/drug effects ; Mammary Neoplasms, Animal/*metabolism ; Mice ; Mice, Inbred BALB C ; }, abstract = {Calmodulin (CaM) is a ubiquitous, calcium-binding protein that regulates several important aspects of cellular metabolism. A number of enzymes such as phosphodiesterase (PDE-1) are stimulated by CaM. In previous studies, our results showed that artemisinin (ART) is a potent inhibitor of CaM and PDE-1 activity. In this study, the effects of dihydroartemisinin (DHA) that is a semisynthesized agent from the ART on CaM structure were investigated. The result showed that DHA increased fluorescence emission of CaM in higher amounts compared with the ART. Also, the effect of DHA on CaM-dependent PDE-1 activity was studied. Kinetic analysis of the DHA-CaM interaction showed that this agent competitively inhibited the activation of PDE-1 without affecting Vmax. Km values of PDE-1 in the presence of ART and DHA were 10 and 15 microM, respectively; DHA increased Km value in higher amounts compared with the ART. The Ki constants for ART and DHA were 10 microM and 7.3 microM, respectively. As a conclusion, CaM and CaM-dependent PDE-1 were inhibited by DHA more than ART. The data indicated that DHA could stimulate the delayed type hypersensitivity (DTH) against sheep blood cells in Balb/c mice and reduced the tumor growth in vivo against invasive ductal carcinoma in Balb/c mice.}, } @article {pmid19898865, year = {2010}, author = {Corte, MD and González, LO and Junquera, S and Bongera, M and Allende, MT and Vizoso, FJ}, title = {Analysis of the expression of hyaluronan in intraductal and invasive carcinomas of the breast.}, journal = {Journal of cancer research and clinical oncology}, volume = {136}, number = {5}, pages = {745-750}, pmid = {19898865}, issn = {1432-1335}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Disease Progression ; Female ; Humans ; Hyaluronic Acid/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {AIMS: To evaluate hyaluronan expression at different stages of tumoral progression in primary breast cancer.

METHODS: Hyaluronan expression was evaluated by histochemical techniques in 42 cases of pure DCIS, in 15 cases of DCIS with a microinvasive component, and in 32 cases of invasive ductal carcinoma of the breast. Staining results were evaluated by calculating the percentage of stained areas by means of a specific software program.

RESULTS: Our results show higher values of hyaluronan expression in invasive breast carcinomas [median of percentage of stained areas 41.1 (range 8-69.2)] and in DCIS with a microinvasive component [48.6 (16.8-62.8)] than in pure DCIS [14.5 (1-44.4)] (p < 0.001, for both).

CONCLUSIONS: Our study indicates a proportionally higher area of hyaluronan expression in DCIS with a microinvasive component than in pure DCIS, suggesting a key role of this glycosaminoglycan in the early invasive phase of breast carcinomas. Thus, hyaluronan could play an important function in determining the migratory phenotype of cancer cells. Larger size tumors appear to demonstrate an intricate balance between hyaluronan synthesis and degradation, thus conditioning intratumoral heterogeneity in the hyaluronan metabolism.}, } @article {pmid19896695, year = {2010}, author = {Macher-Goeppinger, S and Marme, F and Goeppert, B and Penzel, R and Schirmacher, P and Sinn, HP and Aulmann, S}, title = {Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality.}, journal = {Human pathology}, volume = {41}, number = {2}, pages = {293-296}, doi = {10.1016/j.humpath.2009.08.006}, pmid = {19896695}, issn = {1532-8392}, mesh = {Aged ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Loss of Heterozygosity/genetics ; Neoplasms, Multiple Primary/genetics/*pathology/surgery ; Phyllodes Tumor/genetics/*pathology/surgery ; Polymerase Chain Reaction ; }, abstract = {Invasive carcinomas arising within fibroepithelial tumors represent an uncommon manifestation of breast cancer. We report the case of a 70-year-old woman who underwent mastectomy for a malignant phyllodes tumor measuring 6 cm. Histological workup of the specimen revealed a high-grade invasive ductal carcinoma 2.5 cm in diameter within the phyllodes tumor. DNA was isolated from microdissected epithelial and stromal components of the phyllodes tumor as well as from the invasive ductal carcinoma cells. Using multiplex polymerase chain reaction, a comparative allelotyping was performed with a panel of 11 microsatellite markers. The malignant stroma of the phyllodes tumor showed loss of heterozygosity at chromosome 16q23, 17q12, 17q25, and 22q13; the epithelial tumor component shared the loss of 16q23; whereas the invasive carcinoma had lost divergent alleles at 16q23, 17q12, and 17q25, indicating a lack of clonality between phyllodes tumor and invasive ductal carcinoma. Although our data are compatible with a previously postulated common origin of epithelial and stromal components of phyllodes tumors, the coexisting invasive ductal carcinoma appears to represent a true collision tumor.}, } @article {pmid19895711, year = {2009}, author = {Sui, W and Ou, M and Chen, J and Wan, Y and Peng, H and Qi, M and Huang, H and Dai, Y}, title = {Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer.}, journal = {World journal of surgical oncology}, volume = {7}, number = {}, pages = {83}, pmid = {19895711}, issn = {1477-7819}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; China ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/*genetics ; Humans ; *Immunohistochemistry ; *In Situ Hybridization, Fluorescence ; Predictive Value of Tests ; Prospective Studies ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; Tissue Fixation ; }, abstract = {BACKGROUND: The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China.

METHODS: Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results.

RESULTS: A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P<0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+.

CONCLUSION: The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.}, } @article {pmid19893985, year = {2009}, author = {Makdissi, FB and Machado, LV and Oliveira, AG and Benvenuti, TT and Katayama, ML and Brentani, MM and Osório, CA and Mourão Netto, M and Lyra, EC and Carvalho, F and Góes, JC and Folgueira, MA}, title = {Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {42}, number = {12}, pages = {1128-1137}, doi = {10.1590/s0100-879x2009001200002}, pmid = {19893985}, issn = {1414-431X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cadherins/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Epithelial Cells/chemistry ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Snail Family Transcription Factors ; Transcription Factors/genetics/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.}, } @article {pmid19889514, year = {2010}, author = {Christodoulou, MI and Kapsogeorgou, EK and Moutsopoulos, HM}, title = {Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome.}, journal = {Journal of autoimmunity}, volume = {34}, number = {4}, pages = {400-407}, doi = {10.1016/j.jaut.2009.10.004}, pmid = {19889514}, issn = {1095-9157}, mesh = {Adult ; Aged ; Biopsy ; Cell Count ; Cell Movement/*immunology ; Humans ; Immune System/cytology ; Immunohistochemistry ; Leukocytes, Mononuclear ; Middle Aged ; Salivary Glands, Minor/immunology/*pathology ; Sjogren's Syndrome/immunology/*pathology ; Young Adult ; }, abstract = {Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion severity; however, these differences are not well-defined. To investigate the differential distribution of the major infiltrating mononuclear cell (MNC) types in SS-lesions of variable severity, total-T, CD4(+)-T, CD8(+)-T, Treg, and B cell, macrophage (MPhi), interdigitating (iDC) and follicular dendritic cell (fDC), and natural-killer (NK)-cell incidence (%-total infiltrating MNC) was analyzed in MSG biopsies with mild (n = 11), intermediate (n = 13) or severe (n = 15) lesions. T cells, CD4(+)-T cells and Tregs, B lymphocytes, MPhis and iDCs were significantly different among MSG tissues with mild, intermediate or severe inflammatory lesions, while CD8(+)-T cell, fDC and NK cell incidence was not correlated with lesion severity. T cell, CD4(+)-T cell, T/B cell ratio and iDC incidence was negatively, whereas B cell and MPhi incidence was positively correlated with infiltration grade and biopsy focus score. Tregs predominated in intermediate lesions. Multivariate analysis revealed several associations between the incidence of each infiltrating MNC-type and disease manifestations, implying an involvement of local immune responses in systemic disease features. Our findings support that the distribution of infiltrating MNCs at the SS-lesions varies according to lesion severity and correlates with disease manifestations. The significance of this differential distribution and the underlying aetiopathogenic factors need to be elucidated.}, } @article {pmid19889275, year = {2009}, author = {Kayahan, M and Koksal, N and Gunes, P and Uzun, MA and Aliustaoglu, M and Gunerhan, Y and Bugan, U}, title = {Ectopic breast carcinoma.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {19}, number = {11}, pages = {734-736}, pmid = {19889275}, issn = {1022-386X}, mesh = {Adult ; Axilla/pathology ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Choristoma/pathology/*surgery ; Female ; Humans ; }, abstract = {A 47-year-old premenopausal woman had a swelling in right axilla which had been diagnosed as "ectopic breast tissue" with an incisional biopsy. A subcutaneous nodule appeared two years ago. The ectopic breast containing the mass was excised with axillary dissection. It was an invasive ductal carcinoma and metastasis was detected in one lymph node. She received local radiotherapy after 6 cycles of chemotherapy and has now been taking hormonotherapy. Ectopic breast tissue has potential for malignant transformation. As its carcinoma has a worse prognosis and a higher incidence of metastasis because of delayed diagnosis, prophylactic excision may be recommended.}, } @article {pmid19889214, year = {2009}, author = {Provatopoulou, X and Gounaris, A and Kalogera, E and Zagouri, F and Flessas, I and Goussetis, E and Nonni, A and Papassotiriou, I and Zografos, G}, title = {Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {390}, pmid = {19889214}, issn = {1471-2407}, mesh = {Acute-Phase Proteins/genetics/*metabolism ; Adult ; Aged ; Breast Neoplasms/blood/genetics/*metabolism/pathology ; Carcinoma/blood/genetics/*metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Lipocalin-2 ; Lipocalins/blood/genetics/*metabolism ; Matrix Metalloproteinase 9/blood/genetics/*metabolism ; Middle Aged ; Protein Binding ; Proto-Oncogene Proteins/blood/genetics/*metabolism ; }, abstract = {BACKGROUND: Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.

METHODS: The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.

RESULTS: Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.

CONCLUSION: These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.}, } @article {pmid19889024, year = {2010}, author = {Tuettenberg, A and Fondel, S and Steinbrink, K and Enk, AH and Jonuleit, H}, title = {CD40 signalling induces IL-10-producing, tolerogenic dendritic cells.}, journal = {Experimental dermatology}, volume = {19}, number = {1}, pages = {44-53}, doi = {10.1111/j.1600-0625.2009.00975.x}, pmid = {19889024}, issn = {1600-0625}, mesh = {Adenoviridae ; Autocrine Communication ; CD4-Positive T-Lymphocytes/immunology ; CD40 Antigens/*metabolism ; CD40 Ligand/genetics/*metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; *Immunomodulation ; Interleukin-10/*metabolism ; Phenotype ; Receptors, Interleukin-10/metabolism ; Signal Transduction ; }, abstract = {Dendritic cells (DC) are potent antigen-presenting cells capable to induce efficient antigen-specific T cell responses in vitro and in vivo. Herein, the maturation process is of great significance, as immature DC (iDC) are known to induce rather regulatory than effector T cell differentiation. This study was designed to characterize the role of the CD40-CD40L pathway for differentiation and function of human DC. Therefore, iDC were stimulated through CD40-CD40L interaction by transduction of DC with adenoviral vectors encoding for CD40L (Ad-CD40L). Resulting DC (CD40L-DC) were analysed concerning their phenotype, cytokine profile and T cell stimulatory capacity. Transduction induced a DC phenotype comparable to stimulation with proinflammatory cytokines as revealed by upregulation of CD83 and the costimulatory molecules CD80 and CD86. Additionally, Ad-CD40L-induced strong production of IL-12p70 not observed in cytokine-matured DC. Surprisingly, the T cell stimulatory capacity was markedly reduced in CD40L-DC. Furthermore, stimulation of CD8(+) T cells by peptide-loaded CD40L-DC resulted in a substantial reduction of antigen-specific IFN-gamma production. This phenomenon is due to an enhanced IL-10 production of CD40L-DC in DC-T cell coculture as well as a stabilization of the IL-10 receptor expression on activated T cells. These data demonstrate that DC stimulated through CD40-CD40L interaction differentiate into tolerogenic DC with immunomodulatory function.}, } @article {pmid19887523, year = {2010}, author = {Lim, KH and Oh, DY and Chie, EK and Han, W and Im, SA and Kim, TY and Park, IA and Noh, DY and Ha, SW and Bang, YJ}, title = {Metaplastic breast carcinoma: clinicopathologic features and prognostic value of triple negativity.}, journal = {Japanese journal of clinical oncology}, volume = {40}, number = {2}, pages = {112-118}, doi = {10.1093/jjco/hyp139}, pmid = {19887523}, issn = {1465-3621}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*physiopathology ; Carcinoma, Intraductal, Noninfiltrating/blood/*chemistry ; Disease-Free Survival ; Down-Regulation ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Korea ; Metaplasia/*physiopathology ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*blood ; Retrospective Studies ; Tumor Suppressor Protein p53/*blood ; }, abstract = {OBJECTIVE: Metaplastic breast carcinomas (MBC) are a rare type of breast cancer and are generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. There is a paucity of information on prognosis according to hormone receptor and HER2 expression for these rare tumors. The aim of this study was to compare the clinical features and prognosis between triple-negative metaplastic carcinoma (TNMC) and non-triple-negative metaplastic carcinoma (NTNMC).

METHODS: We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. The medical records were reviewed.

RESULTS: Fifty-one patients were identified. At a median follow-up of 40.8 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 75.5% and 86.3%, respectively. Non-triple negativity (P = 0.012) correlated significantly with OS in multivariate analysis. Of the 51 patients, 41 (80.4%) had TNMC and 10 (19.6%) had NTNMC. The two groups did not differ significantly by age, tumor size or nodal status. In patients with NTNMC, the positivity rates for estrogen receptor, progesterone receptor and HER2 were 20.0%, 30.0% and 80.0% in NTNMC. The 3-year OS rates in patients with TNMC and NTNMC were 93.4% and 58.2%, respectively (P = 0.007). With respect to DFS, there was no statistically significant difference between patients with TNMC and those with NTNMC (P = 0.149).

CONCLUSIONS: In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed.}, } @article {pmid19880290, year = {2010}, author = {Charbonnier, LM and Han, WG and Quentin, J and Huizinga, TW and Zwerina, J and Toes, RE and Jorgensen, C and Louis-Plence, P}, title = {Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis.}, journal = {Journal of autoimmunity}, volume = {34}, number = {4}, pages = {390-399}, doi = {10.1016/j.jaut.2009.10.003}, pmid = {19880290}, issn = {1095-9157}, mesh = {Adoptive Transfer/*methods ; Animals ; Arthritis/*therapy ; CD4 Antigens ; Cell Movement ; Dendritic Cells/immunology ; Integrin alpha2 ; Interleukin-10/*metabolism ; Lymph Nodes ; Mice ; T-Lymphocytes, Regulatory/immunology/*transplantation ; Treatment Outcome ; }, abstract = {We have previously demonstrated, in the collagen-induced arthritis model (CIA), that repetitive injections of immature bone-marrow-derived dendritic cells (iDCs) induce the expansion of a population of CD4CD49b-expressing cells, and that their adoptive transfer results in protection against CIA in a prophylactic setting. However, the in vivo mechanism responsible for their expansion, as well as their therapeutic potential in established disease remains to be defined. In the present study, we show that expression of the MHC class II molecules on iDCs is required for their expansion thus identifying these cells as MHC class II-restricted T cells. Using adoptive transfer of Thy1.1 positive cells, it is shown that iDC-induced CD4(+)CD49b(+) T cells home to the lymph nodes draining the inflamed tissue. The high immunomodulatory potential of these cells was underscored following their adoptive transfer in a model of contact hypersensitivity. Finally, we assessed and compared the therapeutic potential of iDC-inducible CD4(+)CD49b(+) T cells with that of iDCs in established CIA. Repetitive injections of iDCs in arthritic mice failed to decrease the severity of established disease. In contrast however, a single injection of iDC-induced CD4(+)CD49b(+) T cells reversed clinical symptoms of arthritis and provided long-lasting protection. Together, our data indicate that iDC-induced CD4(+)CD49b(+) T cells are bona fide T regulatory cells with strong immunomodulatory properties that are not only able to prevent disease onset, but also to interfere with an ongoing inflammatory immune response.}, } @article {pmid19879256, year = {2010}, author = {Sharma, G and Mirza, S and Parshad, R and Srivastava, A and Datta Gupta, S and Pandya, P and Ralhan, R}, title = {CpG hypomethylation of MDR1 gene in tumor and serum of invasive ductal breast carcinoma patients.}, journal = {Clinical biochemistry}, volume = {43}, number = {4-5}, pages = {373-379}, doi = {10.1016/j.clinbiochem.2009.10.009}, pmid = {19879256}, issn = {1873-2933}, mesh = {ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/*genetics/metabolism ; Adult ; Aged ; Breast Neoplasms/*blood/*genetics/pathology ; Carcinoma, Ductal, Breast/*blood/*genetics/pathology ; CpG Islands/*genetics ; DNA Methylation/*genetics ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Survival Analysis ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVES: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), a transmembrane calcium-dependent efflux pump, implicated in drug resistance. In this prospective study, methylation status of MDR1 promoter and its correlation with clinicopathological parameters were evaluated in tumor and serum of breast cancer patients.

DESIGN AND METHODS: Methylation-specific PCR was carried out to investigate the promoter methylation status of MDR1 in tumor and serum of 100 patients with invasive ductal carcinomas of breast (IDCs). The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.

RESULTS: MDR1 was hypomethylated in 47% tumors and 44% paired sera of IDC patients and correlated significantly with increased tumor size and advanced tumor stage. Promoter hypomethylation of MDR1 in serum DNA showed 98% specificity and 50% sensitivity.

CONCLUSIONS: Hypomethylation of MDR1 promoter in IDCs accounted for P-gp overexpression and aggressive biologic behavior in a subset of patients. Detection of these epigenetic changes in circulating DNA may not only enhance insight into the biological behavior of the primary tumor of an individual but may also provide valuable information regarding prognosis that can be readily monitored throughout the disease course.}, } @article {pmid19877191, year = {2010}, author = {Lott, DG and Dan, O and Lu, L and Strome, M}, title = {Decoy NF-kappaB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T cells.}, journal = {The Laryngoscope}, volume = {120}, number = {1}, pages = {44-52}, doi = {10.1002/lary.20667}, pmid = {19877191}, issn = {1531-4995}, mesh = {Animals ; Dendritic Cells/*immunology ; Immunosuppression Therapy/*methods ; Larynx/*transplantation ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; NF-kappa B/*physiology ; T-Lymphocytes, Regulatory/*immunology ; Transplantation, Homologous ; }, abstract = {OBJECTIVES/HYPOTHESIS: The increased risk of malignancy associated with post-transplant immunosuppression limits the potential of laryngeal transplantation as a reconstructive option. This risk may be mitigated by utilizing decoy nuclear factor kappa B (NF-kappaB) immature dendritic cells (iDC) to provide donor-specific tolerance. The purpose of this study was to explore whether tolerogenic properties of iDC can be applied to composite tissue transplantation.

STUDY DESIGN: Animal study.

METHODS: Five iDC-injected mice were euthanized at 15, 30, and 60 days post-laryngeal transplant. Control groups included five transplanted mice without immunosuppression, one iDC-injected mouse euthanized prior to transplantation, one mouse without injection or transplantation, and one mouse administered mature DC to serve as an accelerated rejection control. Larynges were graded for rejection severity according to a grading scale. Draining lymph nodes and spleens were evaluated by flow cytometry to determine immunogenic activity of iDC and T cells locally and peripherally.

RESULTS: Each time group demonstrated moderate allograft rejection (rejection severity scores: 4.38, 5.10, 5.29). NF-kappaB iDC-treated mice had significantly less rejection at all time points compared to nonimmunosuppressed mice. Flow cytometry showed inhibition of cytotoxic T cell infiltration and expansion of regulatory T cells at the allograft site.

CONCLUSIONS: iDC immunosuppression maintains laryngeal allograft integrity up to 60 days post-transplantation. Regulatory T cells are enhanced at the allograft site, which serves to suppress immune cell activation and induce self-antigen tolerance. iDC injection may lessen post-transplant comorbidities by decreasing the systemic immune response and favorably affecting concurrent immunosuppressive dose sequencing for laryngeal allograft preservation.}, } @article {pmid19876578, year = {2009}, author = {Peres, RM and Derchain, SF and Heinrich, JK and Serra, KP and Pinto, GA and Soares, FA and Sarian, LO}, title = {[ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma].}, journal = {Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia}, volume = {31}, number = {9}, pages = {461-467}, doi = {10.1590/s0100-72032009000900007}, pmid = {19876578}, issn = {1806-9339}, mesh = {Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*metabolism/pathology ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2/analysis/*biosynthesis ; Receptors, Estrogen/analysis/*biosynthesis ; Receptors, Progesterone/analysis/*biosynthesis ; }, abstract = {PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively).

METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5% (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas.

RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample).

CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.}, } @article {pmid19853438, year = {2011}, author = {Nihon-Yanagi, Y and Ueda, T and Kameda, N and Okazumi, S}, title = {A case of ectopic breast cancer with a literature review.}, journal = {Surgical oncology}, volume = {20}, number = {1}, pages = {35-42}, doi = {10.1016/j.suronc.2009.09.005}, pmid = {19853438}, issn = {1879-3320}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anastrozole ; Antineoplastic Agents, Hormonal/administration & dosage ; Breast Neoplasms/drug therapy/epidemiology/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology ; *Choristoma ; Female ; Humans ; Japan/epidemiology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Nitriles/administration & dosage ; Survival Analysis ; Treatment Outcome ; Triazoles/administration & dosage ; }, abstract = {A 63-year-old woman was referred to our hospital because of a right axillary nodule in 2004. Physical examination showed a spherical nodule measuring 0.5cm in diameter in the right axilla. No mass was palpable in either breast. Mammograms were normal. Ultrasonography revealed a subcutaneous hypoechoic mass 0.7mm in maximum diameter in the right axilla. The patient underwent an excisional biopsy. Histological examination revealed an invasive ductal carcinoma (scirrhous carcinoma) in ectopic breast tissue. The patient subsequently underwent a wide local excision of the tissue surrounding the biopsy scar, with axillary lymph node dissection. Histologically, no residual tumor or nodal metastasis was found. Postoperatively, she received endocrine therapy and remains well, without any evidence of recurrence 4 years 10 months after operation. Cancer of the ectopic breast tissue is rare, and most cases present as a solitary axillary mass. Long-term outcomes remain unclear. We present a case of breast carcinoma in the axillary ectopic mammary gland and summarize the clinical features of 94 cases, including ours, in Japan. We also compare long-term survival between ectopic breast cancer and usual breast cancer according to TNM T stage and lymph node metastasis.}, } @article {pmid19850995, year = {2008}, author = {Farese, SA and Aebi, S}, title = {Infiltrating lobular carcinoma of the breast: systemic treatment.}, journal = {Breast disease}, volume = {30}, number = {}, pages = {45-52}, doi = {10.3233/BD-2009-0281}, pmid = {19850995}, issn = {1558-1551}, mesh = {Antineoplastic Agents/*therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Aromatase Inhibitors/therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Carcinoma, Lobular/*drug therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Neoadjuvant Therapy ; }, abstract = {Invasive lobular carcinoma (ILC) is the second most common type of breast cancer after invasive ductal carcinoma (IDC). It is characterized by unique clinical, biological and molecular properties. ILC is almost always positive for the estrogen receptor and is typically of a lower grade compared with IDC. We have reviewed selected literature on preoperative (neoadjuvant) and adjuvant systemic therapy of breast cancer focusing on the differential therapy of ILC. Despite the importance of this type of breast cancer, information about its specific treatment is sparse, in particular with regard to adjuvant systemic chemotherapy. ILC has significantly lower rates of response to neoadjuvant chemotherapy compared with IDC; however, the low chemosensitivity seems not to result in a survival disadvantage. Adjuvant hormonal therapy studies do not distinguish between ILC and IDC. Thus, recommendations about endocrine therapies are made using the same criteria as for IDC.}, } @article {pmid19850993, year = {2008}, author = {Dedes, KJ and Fink, D}, title = {Clinical presentation and surgical management of invasive lobular carcinoma of the breast.}, journal = {Breast disease}, volume = {30}, number = {}, pages = {31-37}, doi = {10.3233/BD-2009-0277}, pmid = {19850993}, issn = {1558-1551}, mesh = {Breast Neoplasms/*diagnosis/*surgery ; Carcinoma, Lobular/*diagnosis/*surgery ; Female ; Humans ; Middle Aged ; Survival Analysis ; }, abstract = {Invasive lobular carcinoma is the second most common histological type of breast cancer and differs from invasive ductal carcinoma also in some clinical features. Multifocal or multicentric as well as contralateral diseases are more frequently found among patients with lobular carcinoma. Tumor size at diagnosis is larger than in patients with ductal carcinoma due to diagnostic challenges associated with lobular histology. For surgical management, breast conserving surgery followed by radiotherapy offers equal local control as mastectomy. Controversy however exists regarding risk for positive margins and subsequent need for second operations. Axillary staging can be safely performed by sentinel node biopsy if lymph nodes are clinically negative, even in multifocal or multicentric disease.}, } @article {pmid19846819, year = {2009}, author = {Renshaw, MA and Renshaw, AA and Gould, EW}, title = {Should pathologists send all or only selected slides for patient-requested interlaboratory second opinion?.}, journal = {American journal of clinical pathology}, volume = {132}, number = {5}, pages = {763-766}, doi = {10.1309/AJCP55VZZLQEHPPS}, pmid = {19846819}, issn = {1943-7722}, mesh = {Breast Neoplasms/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Diagnostic Errors/*prevention & control ; Female ; Humans ; Pathology, Clinical/*standards ; Referral and Consultation/*standards ; Reproducibility of Results ; }, abstract = {For interlaboratory second opinions requested by patients or clinicians, whether all or selected slides should be sent is unknown. We compared the disagreement rate for requested second opinions for 4 years of sending selected slides with the rate for 1 year of sending all slides. Disagreements were identified in 81 (13.6%) of 596 cases (468 selected slides, 128 all slides). The disagreement rate was less when sending selected slides (n = 58 [12%]) vs all slides (n = 23 [18%]; P = .03). Only 5 cases were identified with disagreement related to whether all or selected slides were sent (selected slides, 1 case [slide of interest inadvertently not chosen]; all slides, 4 cases; P = .03). When all slides were sent (disagreement in number of positive nodes, 2 cases; failure of second laboratory to identify microinvasive ductal carcinoma when present in 1 of 10 core biopsy slides, and ductal carcinoma in situ [DCIS] adjacent to invasive ductal carcinoma when DCIS present on only 1 of 5 slides [2/81 (2%)], 1 case each). Sending all slides is associated with a higher disagreement rate than sending only selected slides, but this disagreement comes from correcting and introducing error.}, } @article {pmid19844653, year = {2009}, author = {Amano, H and Miura, F and Toyota, N and Wada, K and Katoh, K and Hayano, K and Kadowaki, S and Shibuya, M and Maeno, S and Eguchi, T and Takada, T and Asano, T}, title = {Is pancreatectomy with arterial reconstruction a safe and useful procedure for locally advanced pancreatic cancer?.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {16}, number = {6}, pages = {850-857}, doi = {10.1007/s00534-009-0190-7}, pmid = {19844653}, issn = {1436-0691}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/pathology/*surgery ; Female ; Hepatic Artery/*surgery ; Humans ; Male ; Medical Illustration ; Mesenteric Artery, Superior/*surgery ; Middle Aged ; Neoplasm Invasiveness ; Pancreatectomy/*methods/mortality ; Pancreatic Neoplasms/pathology/*surgery ; Pancreaticoduodenectomy/*methods/mortality ; Portal Vein/surgery ; Retrospective Studies ; }, abstract = {BACKGROUND/PURPOSE: We often encounter unresectable pancreatic cancer due to invasions of the major vessels. Vascular resection for locally advanced pancreatic cancers has an advantage in en block local resection. There are potential cases in which good outcomes can be achieved by arterial resection.

METHODS: Pancreatectomy (including total pancreatectomy in 15 cases, pancreatoduodenectomy in 7 cases and distal pancreatectomy in one case) was performed in 23 cases of invasive ductal carcinoma of the pancreas, in combination with resection and reconstruction of the hepatic artery in 15 cases, the superior mesenteric artery in 12 cases (there are overlaps) and the portal vein in 20 cases.

RESULTS: The median operating time was 686 min (416-1,190 min) and the median blood loss was 2,830 ml (440-19,800 ml). This shows that the surgery was highly-invasive. The operative mortality rate was 4.3%. On the basis of the UICC classification, there were 2 cases of Stage IIa, 4 cases of Stage IIb, 9 cases of Stage III, 8 cases of Stage IV, while there were 18 cases (78.3%) of R0 resection. On the other hand, the final histological findings showed that there were 8 cases (34.8%) of M1 (liver and non-regional lymph node metastases), so it is thought that decisions on operative indications should be not be made slightly. As for the overall survival rate, the 1-year survival rate was 51.2% and the 3-year survival rate was 23.1% while the median survival time (MST) was 12 months. As for 15 cases of M0, the 1-year survival rate was 61.9% and the 4-year survival rate was 38.7% while the MST was 16 months. On the other hand, the MST was poor (10 months) in 8 cases of M1, showing that a statistically significant difference was observed depending upon the degree of metastasis (log-rank P = 0.0409). In 18 cases of R0, the 1-year survival rate was 67.2%, the 4-year survival rate 30.2% and the MST 13 months, respectively, while in 5 cases of R1 and R2, the MST was 6 months, showing that there was a statistically significant difference between R0 cases and R1, R2 cases (log-rank P = 0.0002).

CONCLUSIONS: Further discussion is required concerning surgical indications and significance. However, it is thought that resection is useful only when surgery of R0 has taken place for selected locally advanced pancreatic cancer (M0).}, } @article {pmid19838723, year = {2010}, author = {Kim, HS and Seok, JH and Cha, ES and Kang, BJ and Kim, HH and Seo, YJ}, title = {Significance of nipple enhancement of Paget's disease in contrast enhanced breast MRI.}, journal = {Archives of gynecology and obstetrics}, volume = {282}, number = {2}, pages = {157-162}, doi = {10.1007/s00404-009-1244-4}, pmid = {19838723}, issn = {1432-0711}, mesh = {Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/*pathology/surgery ; Retrospective Studies ; }, abstract = {PURPOSE: To evaluate significance of nipple enhancement of Paget's disease in contrast enhanced (CE) breast MRI.

METHODS: Ten patients of biopsy proven Paget's disease were included in this study. Preoperative mammogram and ultrasonogram (US) were obtained in all 10 patients, and 8 patients underwent CE breast MRI prior to surgery. Mammographic and US findings were reviewed retrospectively. On MRI, morphology (flattening or asymmetry or thickening) and enhancement of pathologically involved nipple were analyzed comparing with the opposite side, and also reviewed the abnormal enhancing lesion in the breast parenchyma.

RESULTS: Morphologic changes of the nipple were detected in 2 out of 10 patients by mammogram and 6 out of 10 patients by US. On MRI, morphologic change was also revealed in 7 patients and abnormal enhancement of involved nipple was observed in all 8 patients. Associated parenchymal enhancing lesions were proved to be DCIS (7 out of 10) and invasive ductal carcinoma (2 out of 10). Remaining one patient had no underlying breast parenchymal malignancy.

CONCLUSION: CE breast MRI allows for the correct detection of nipple involvement of Paget's disease even when clinical information or mammographic/US findings are not provided.}, } @article {pmid19836270, year = {2010}, author = {Jansen, SA and Fan, X and Yang, C and Shimauchi, A and Karczmar, G and Newstead, GM}, title = {Relating dose of contrast media administered to uptake and washout of malignant lesions on DCEMRI of the breast.}, journal = {Academic radiology}, volume = {17}, number = {1}, pages = {24-30}, doi = {10.1016/j.acra.2009.06.015}, pmid = {19836270}, issn = {1878-4046}, mesh = {Breast Neoplasms/*metabolism/*pathology ; Contrast Media/*administration & dosage ; Dose-Response Relationship, Drug ; Female ; Gadolinium DTPA/administration & dosage/*pharmacokinetics ; Humans ; Magnetic Resonance Imaging/*methods ; Metabolic Clearance Rate/drug effects ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {RATIONALE AND OBJECTIVES: To quantify the relationship between dose of contrast administered and contrast kinetics of malignant breast lesions.

MATERIALS AND METHODS: A total of 108 patients with 120 malignant lesions were selected for an institutional review board-approved review. Dynamic magnetic resonance protocol: one pre- and three or five post-contrast (at a fixed volume of 20 mL of 0.5 M gadodiamide) images. Patients were stratified into groups based on dose of contrast administered, after calculation of body weight (kg): Dose Group 1, <0.122 mmol/kg; Dose Group 2, 0.123-0.155 mmol/kg; Dose Group, 3 > 0.155 mmol/kg. Analysis of kinetic curve shape was made according to the Breast Imaging Reporting and Data System lexicon. Several quantitative parameters were calculated including initial and peak enhancement percentage (E(1) and E(peak)). Linear regression was used to model the variation of kinetic parameters with dose.

RESULTS: There was no difference found in the qualitative Breast Imaging Reporting and Data System descriptors of curve shape between the three dose groups. There was a trend for E(1) and E(peak) to increase from Dose Group 1 to Dose Group 3 in malignant lesions overall, as well as in invasive ductal carcinoma lesions separately. Each decrement/increment of 0.05 mmol/kg in dose yielded a decrease/increase of 78% and 97% in E(1) for in situ and invasive cancers, respectively.

CONCLUSION: Contrast should be administered at fixed dose to achieve comparable levels of lesion uptake in women of different weights. Our results suggest that reducing the contrast administered to 0.05 mmol/kg, as has been suggested for patients at risk of developing nephrogenic systemic fibrosis, could substantially decrease the observed initial enhancement in some cancers.}, } @article {pmid19836055, year = {2010}, author = {Hasebe, T and Tamura, N and Okada, N and Hojo, T and Akashi-Tanaka, S and Shimizu, C and Tsuda, H and Shibata, T and Sasajima, Y and Iwasaki, M and Kinoshita, T}, title = {p53 expression in tumor-stromal fibroblasts is closely associated with the nodal metastasis and outcome of patients with invasive ductal carcinoma who received neoadjuvant therapy.}, journal = {Human pathology}, volume = {41}, number = {2}, pages = {262-270}, doi = {10.1016/j.humpath.2009.07.021}, pmid = {19836055}, issn = {1532-8392}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Disease-Free Survival ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/metabolism ; Female ; Fibroblasts/*metabolism/pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis/*pathology ; Middle Aged ; Multivariate Analysis ; *Neoadjuvant Therapy ; Neoplasm Recurrence, Local/metabolism/pathology ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Treatment Outcome ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The purpose of this study was to determine whether p53 immunoreactivity in tumor-stromal fibroblasts assessed by the Allred scoring system in biopsy specimens obtained before neoadjuvant therapy and assessed in surgical specimens obtained after neoadjuvant therapy is significantly associated with nodal metastasis by invasive ductal carcinoma and with the outcome of 318 patients with invasive ductal carcinoma who received neoadjuvant therapy, according to UICC pathologic TNM stage, in multivariate analyses with well-known clinicopathologic factors. The Allred scores for p53 in tumor-stromal fibroblasts in the surgical specimens were significantly associated with the presence of nodal metastasis. The Allred scores for p53 in the tumor-stromal fibroblasts of biopsy and surgical specimens were a very important outcome predictive factor for patients who received neoadjuvant therapy, independent of UICC pathologic TNM status, but the outcome predictive power of the Allred scores for p53 in tumor-stromal fibroblasts assessed in the surgical specimens was superior to that of the Allred scores for p53 in tumor-stromal fibroblasts in the biopsy specimens. The results indicated a close association between p53 protein expression in tumor-stromal fibroblasts, especially in surgical specimens, and both the presence of nodal metastasis and the outcome of invasive ductal carcinoma patients who received neoadjuvant therapy.}, } @article {pmid19825003, year = {2010}, author = {Ingegnoli, A and d'Aloia, C and Frattaruolo, A and Pallavera, L and Martella, E and Crisi, G and Zompatori, M}, title = {Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.}, journal = {The breast journal}, volume = {16}, number = {1}, pages = {55-59}, doi = {10.1111/j.1524-4741.2009.00850.x}, pmid = {19825003}, issn = {1524-4741}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*methods ; Breast Neoplasms/epidemiology/*pathology/physiopathology ; Carcinoma in Situ/epidemiology/*pathology/physiopathology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Cohort Studies ; Female ; Humans ; Hyperplasia/epidemiology/pathology ; Immunohistochemistry ; Incidence ; Male ; Mammography/methods ; Middle Aged ; Precancerous Conditions/epidemiology/*pathology ; Prognosis ; Retrospective Studies ; Risk Assessment ; }, abstract = {This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.}, } @article {pmid19821109, year = {2009}, author = {Song, Y and Wang, Z and Xu, H and Yue, Z and Xing, C}, title = {Paget's disease is associated with eleven cancerous regions: a case report and therapeutic strategy.}, journal = {Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban}, volume = {29}, number = {5}, pages = {677-678}, pmid = {19821109}, issn = {1672-0733}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Mammography ; Mastectomy ; Middle Aged ; *Neoplasms, Multiple Primary/pathology ; Paget's Disease, Mammary/*pathology/surgery ; }, abstract = {Paget's disease of the breast is an uncommon disorder that accounts for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget's disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget's disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget's disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.}, } @article {pmid19816803, year = {2009}, author = {Kelle, A}, title = {Ensuring the security of synthetic biology-towards a 5P governance strategy.}, journal = {Systems and synthetic biology}, volume = {3}, number = {1-4}, pages = {85-90}, pmid = {19816803}, issn = {1872-5325}, abstract = {Over recent years the label "synthetic biology" has been attached to a number of diverse research and commercial activities, ranging from the search for a minimal cell to the quick delivery of customized genes by DNA synthesis companies. Based on the analysis of biosecurity issues surrounding synthetic biology during the SYNBIOSAFE project, this paper will first provide a rationale for taking security, in addition to safety aspects of this new field, seriously. It will then take stock of the initiatives and measures that have already been taken in this area and will lastly try to map out future areas of activities in order to minimise the security risks emanating from this promising new field of scientific inquiry and technological progress.}, } @article {pmid19812188, year = {2009}, author = {Miksa, M and Wu, R and Dong, W and Komura, H and Amin, D and Ji, Y and Wang, Z and Wang, H and Ravikumar, TS and Tracey, KJ and Wang, P}, title = {Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected].}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {9}, pages = {5983-5990}, pmid = {19812188}, issn = {1550-6606}, support = {R01 AG028352/AG/NIA NIH HHS/United States ; R01 GM062508/GM/NIGMS NIH HHS/United States ; R01 GM057468/GM/NIGMS NIH HHS/United States ; R01 GM053008/GM/NIGMS NIH HHS/United States ; R01 GM053008-15/GM/NIGMS NIH HHS/United States ; R01 GM057468-12/GM/NIGMS NIH HHS/United States ; R01//PHS HHS/United States ; R01 GM062508-07/GM/NIGMS NIH HHS/United States ; R01 AG028352-04/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Antigens, Surface/administration & dosage/*physiology ; Apoptosis Regulatory Proteins/administration & dosage/antagonists & inhibitors/physiology ; Cell Differentiation/*immunology ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology/pathology ; Exosomes/*immunology/*metabolism ; Inflammation Mediators/administration & dosage/antagonists & inhibitors/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Milk Proteins/administration & dosage/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/administration & dosage ; Sepsis/immunology/*metabolism/pathology/*therapy ; }, abstract = {Sepsis, a highly lethal systemic inflammatory syndrome, is associated with increases of proinflammatory cytokines (e.g., TNF-alpha, HMGB1) and the accumulation of apoptotic cells that have the potential to be detrimental. Depending on the timing and tissue, prevention of apoptosis in sepsis is beneficial; however, thwarting the development of secondary necrosis through the active removal of apoptotic cells by phagocytosis may offer a novel anti-sepsis therapy. Immature dendritic cells (IDCs) release exosomes that contain milk fat globule EGF factor VIII (MFGE8), a protein required to opsonize apoptotic cells for phagocytosis. In an experimental sepsis model using cecal ligation and puncture, we found that MFGE8 levels decreased in the spleen and blood, which was associated with impaired apoptotic cell clearance. Administration of IDC-derived exosomes promoted phagocytosis of apoptotic cells and significantly reduced mortality. Treatment with recombinant MFGE8 was equally protective, whereas MFGE8-deficient mice suffered from increased mortality. IDC exosomes also attenuated the release of proinflammatory cytokines in septic rats. Liberation of HMGB1, a nuclear protein that contributes to inflammation upon release from unengulfed apoptotic cells, was prevented by MFGE8-mediated phagocytosis in vitro. We conclude that IDC-derived exosomes attenuate the acute systemic inflammatory response in sepsis by enhancing apoptotic cell clearance via MFGE8.}, } @article {pmid19811884, year = {2010}, author = {Graesslin, O and Antoine, M and Chopier, J and Seror, JY and Flahault, A and Callard, P and Daraï, E and Uzan, S}, title = {Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {36}, number = {2}, pages = {170-175}, doi = {10.1016/j.ejso.2009.09.002}, pmid = {19811884}, issn = {1532-2157}, mesh = {Adult ; Aged ; *Biopsy, Needle/instrumentation/methods ; Breast Neoplasms/metabolism/*pathology/surgery ; Cadherins/analysis ; Epithelium/pathology ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Keratin-5/analysis ; Keratin-6/analysis ; *Mastectomy, Segmental ; Middle Aged ; Stereotaxic Techniques ; }, abstract = {BACKGROUND: Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery.

DESIGN: From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought.

RESULTS: VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH).

CONCLUSION: ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended.}, } @article {pmid19811434, year = {2009}, author = {Cruz-Robles, D and Chávez-González, JP and Cavazos-Quero, MM and Pérez-Méndez, O and Reyes, PA and Vargas-Alarcón, G}, title = {Association between IL-1B and IL-1RN gene polymorphisms and Chagas' disease development susceptibility.}, journal = {Immunological investigations}, volume = {38}, number = {3-4}, pages = {231-239}, doi = {10.1080/08820130902729637}, pmid = {19811434}, issn = {1532-4311}, mesh = {Cardiomyopathy, Dilated/genetics ; Chagas Cardiomyopathy/*genetics ; Chagas Disease/genetics ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein/*genetics ; Interleukin-1beta/*genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; }, abstract = {Though it is known that the immune system exerts some influence on the resistance against T. cruzi infection its precise role in this process is not well-understood. Some IL-1B alleles and haplotypes have been associated with susceptibility to inflammatory, autoimmune and infectious diseases. The objective of this study was to determine and compare the distribution of IL-1B and IL-1 receptor antagonist (IL-1RN) polymorphisms among T. cruzi seropositive patients, patients with idiopathic dilated cardiomyopathy (IDC) and healthy individuals. We studied 86 individuals seropositive for T. cruzi (58 patients with chronic chagasic cardiomyopathy (CCC) and 28 asymptomatics), 50 seronegative individuals with IDC and 109 healthy individuals. IL-1B-511, IL-1F10.3 IL-1RN.4, IL-1RN 6/1, and IL-1RN 6/2 polymorphisms were analyzed using real-time PCR allelic discrimination technology. Infected patients presented an increased frequency of the CC genotype of the IL-1RN.4 polymorphism when compared to IDC (pC = 0.028; OR = 11.46). The C allele of this polymorphism was found increased in CCC when compared with IDC (pC = 0.036; OR = 0.5) and with controls (pC = 0.035; OR = 1.87). CC genotype of IL-1RN.4 polymorphism was increased in patients with CCC when compared to IDC (pC = 0.0018; OR = 16.74) and healthy individuals (pC = 0.011; OR = 3.6). There is an evident association between the IL1RN.4 polymorphism, T. cruzi infection and CCC development.}, } @article {pmid19811289, year = {2009}, author = {Fehr, EM and Kierschke, S and Max, R and Gerber, A and Lorenz, HM and Schiller, M}, title = {Apototic cell-derived membrane vesicles induce CD83 expression on human mdDC.}, journal = {Autoimmunity}, volume = {42}, number = {4}, pages = {322-324}, doi = {10.1080/08916930902832173}, pmid = {19811289}, issn = {1607-842X}, mesh = {Antigens, CD/*biosynthesis/immunology ; Apoptosis/*immunology ; Autoantigens/immunology ; Cell Communication/immunology ; Cell Membrane/*immunology ; Cytoplasmic Vesicles/immunology ; Dendritic Cells/*immunology/metabolism ; Humans ; Immunoglobulins/*biosynthesis/immunology ; Membrane Glycoproteins/*biosynthesis/immunology ; Phagocytes/immunology ; }, abstract = {A characteristic of apo cell death is the shedding of membrane vesicles from the dying cell. This process is also referred to as apo membrane blebbing. These apo particles contain various autoantigens and are effectively engulfed by phagocytes. A defective phagocytosis has been described in autoimmune diseases like systemic lupus erythematosus and this defect might lead to an accumulation of apo cells and bodies. Thus, we investigated the interactions between apototic cell-derived membrane vesicles (ACdMV), and myeloid dendritic cell (DC). ACdMV were isolated from the supernatant of apo lymphocytes. These isolated ACdMV were morphologically characterized as membrane coated vesicles of an average size of 500 nm. Coincubating isolated ACdMV with iDC we observed CD83 surface expression of the latter. Accumulation of ACdMV may contribute to an inflammatory immune response in autoimmune diseases.}, } @article {pmid19806450, year = {2010}, author = {Kim, HS and Yom, CK and Kim, HJ and Lee, JW and Sohn, JH and Kim, JH and Park, YL and Ahn, SH}, title = {Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy.}, journal = {Breast cancer research and treatment}, volume = {121}, number = {3}, pages = {777-788}, doi = {10.1007/s10549-009-0560-5}, pmid = {19806450}, issn = {1573-7217}, mesh = {Adult ; Age Distribution ; Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/*drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/*metabolism/pathology/secondary ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; Tamoxifen/*therapeutic use ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35-50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35-50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105-3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.}, } @article {pmid19804500, year = {2010}, author = {Takaki, A and Tatsukawa, M and Iwasaki, Y and Koike, K and Noguchi, Y and Shiraha, H and Sakaguchi, K and Nakayama, E and Yamamoto, K}, title = {Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells.}, journal = {Journal of viral hepatitis}, volume = {17}, number = {8}, pages = {555-562}, pmid = {19804500}, issn = {1365-2893}, mesh = {Adult ; Cell Polarity/immunology ; Cytokines/immunology ; Dendritic Cells/cytology/*immunology ; Flow Cytometry ; Hepacivirus/*immunology ; Hepatitis C, Chronic/*immunology/virology ; Humans ; Lymphocyte Activation/immunology ; Male ; Plasmids/immunology ; Recombinant Proteins/*immunology ; Statistics, Nonparametric ; Th1 Cells/*immunology ; Viral Nonstructural Proteins/*immunology ; }, abstract = {Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.}, } @article {pmid19803589, year = {2009}, author = {Liberman, V and Boehm, JK and Lyubomirsky, S and Ross, LD}, title = {Happiness and memory: affective significance of endowment and contrast.}, journal = {Emotion (Washington, D.C.)}, volume = {9}, number = {5}, pages = {666-680}, doi = {10.1037/a0016816}, pmid = {19803589}, issn = {1931-1516}, mesh = {Adaptation, Psychological ; Adult ; *Affect ; Attention ; *Conflict, Psychological ; Cross-Cultural Comparison ; Culture ; Emotions ; Female ; *Happiness ; Humans ; Individuality ; Internal-External Control ; Israel ; Judgment ; *Life Change Events ; Male ; *Mental Recall ; Quality of Life/psychology ; Resilience, Psychological ; *Self Concept ; Surveys and Questionnaires ; *Temperament ; United States ; Young Adult ; }, abstract = {Three studies (two conducted in Israel and one in the United States) examined associations between self-rated dispositional happiness and tendencies to treat memories of positive and negative events as sources of enhanced or attenuated happiness through the use of "endowment" and "contrast." Although participants generally endorsed items describing happiness-enhancing tendencies more than happiness-diminishing ones, self-reported happiness was associated with greater endorsement of "positive endowment" items and less endorsement of "negative endowment" items, and also with less endorsement of items that involved contrasting the present with happier times in the past. Only in the American sample, however, was happiness associated with greater endorsement of items that involved contrasting the present with less happy times in the past. These data suggest that relatively unhappy people show somewhat conflicting memorial tendencies vis-à-vis happiness, whereas very happy people show simpler, and less conflicting, tendencies. These findings augment the existing literatures on the affective consequences of memory, which have been concerned more with mood than with temperament and/or have dealt only with a subset of the endowment and contrast tendencies explored in the present work.}, } @article {pmid19802703, year = {2009}, author = {Csankovszki, G and Petty, EL and Collette, KS}, title = {The worm solution: a chromosome-full of condensin helps gene expression go down.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {17}, number = {5}, pages = {621-635}, pmid = {19802703}, issn = {1573-6849}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; R01 GM079533-02/GM/NIGMS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; T32 GM07544/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics ; Animals ; Caenorhabditis elegans/*genetics ; DNA-Binding Proteins/*genetics ; Dosage Compensation, Genetic ; Female ; *Gene Expression Regulation ; Male ; Multiprotein Complexes/*genetics ; *X Chromosome ; }, abstract = {Dosage compensation in the nematode Caenorhabditis elegans is achieved by the binding of a condensin-like dosage compensation complex (DCC) to both X chromosomes in hermaphrodites to downregulate gene expression two-fold. Condensin I(DC), a sub-part of the DCC, differs from the mitotic condensin I complex by a single subunit, strengthening the connection between dosage compensation and mitotic chromosome condensation. The DCC is targeted to X chromosomes by initial binding to a number of recruiting elements, followed by dispersal or spreading to secondary sites. While the complex is greatly enriched on the X chromosomes, many sites on autosomes also bind the complex. DCC binding does not correlate with DCC-mediated repression, suggesting that the complex acts in a chromosome-wide manner, rather than on a gene-by-gene basis. Worm dosage compensation represents an excellent model system to study how condensin-mediated changes in higher order chromatin organization affect gene expression.}, } @article {pmid19801514, year = {2009}, author = {Turner, MS and Kane, LP and Morel, PA}, title = {Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {8}, pages = {4895-4903}, pmid = {19801514}, issn = {1550-6606}, support = {R01 GM080398-02/GM/NIGMS NIH HHS/United States ; T32 CA082084-10/CA/NCI NIH HHS/United States ; 5T32CA82084-10/CA/NCI NIH HHS/United States ; R01 GM080398-03/GM/NIGMS NIH HHS/United States ; R01 GM080398/GM/NIGMS NIH HHS/United States ; T32 CA082084/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies/immunology ; Antigens/*immunology ; CD28 Antigens/drug effects/immunology/metabolism ; CD3 Complex/drug effects/immunology/metabolism ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Carrier Proteins/immunology/metabolism ; Coculture Techniques ; Cytokines/biosynthesis/immunology ; Dendritic Cells/*immunology/metabolism ; Diabetes Mellitus, Type 1/*immunology ; Dose-Response Relationship, Immunologic ; Forkhead Transcription Factors/immunology ; Interleukin-6/genetics/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Oncogene Protein v-akt/immunology/metabolism ; Ovalbumin/immunology ; Peptides/immunology ; Phosphotransferases (Alcohol Group Acceptor)/immunology/metabolism ; Receptors, Antigen, T-Cell/immunology/metabolism ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism ; TOR Serine-Threonine Kinases ; }, abstract = {The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4(+) T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3(+) Treg. Furthermore, unpulsed mDC, but not iDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3(neg) Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-transgenic T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with Ag dose and inversely with Treg expansion. Studies with T cells or DC from IL-6(-/-) mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low Ag doses. These studies indicate that the strength of Akt/mTOR signaling, a critical T cell-intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production.}, } @article {pmid19800459, year = {2009}, author = {Bharat, A and Gao, F and Margenthaler, JA}, title = {Tumor characteristics and patient outcomes are similar between invasive lobular and mixed invasive ductal/lobular breast cancers but differ from pure invasive ductal breast cancers.}, journal = {American journal of surgery}, volume = {198}, number = {4}, pages = {516-519}, doi = {10.1016/j.amjsurg.2009.06.005}, pmid = {19800459}, issn = {1879-1883}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Carcinoma, Lobular/mortality/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: The aim of this study was to investigate the clinical characteristics associated with invasive lobular cancer (ILC) and mixed invasive ductal cancer (IDC) and ILC compared with IDC.

METHODS: From 1996 to 2006, 4,336 patients with IDC, ILC, and mixed breast cancers were identified. Clinical variables were compared using chi(2) and Fisher's exact tests. Kaplan-Meier survival curves were constructed.

RESULTS: Patients included 3,595 (83%) with IDC, 480 (11%) with ILC, and 261 (6%) with mixed cancers. Patients with ILC and mixed cancers were more likely to have low-grade and estrogen-positive and progesterone-positive tumors but were diagnosed at higher stages of disease compared with patients with IDC (P < .05 for each). Patients with IDC had the poorest 5-year (80%) and 10-year (61%) survival compared with patients with ILC (87% and 68%) and mixed (84% and 69%) cancers (P = .029).

CONCLUSIONS: Although patients with ILC and "mixed" cancers are diagnosed with more advanced disease, their survival is superior to patients with IDC.}, } @article {pmid19800450, year = {2009}, author = {Killelea, BK and Gillego, A and Kirstein, LJ and Asad, J and Shpilko, M and Shah, A and Feldman, S and Boolbol, SK}, title = {George Peters Award: How does breast-specific gamma imaging affect the management of patients with newly diagnosed breast cancer?.}, journal = {American journal of surgery}, volume = {198}, number = {4}, pages = {470-474}, doi = {10.1016/j.amjsurg.2009.06.016}, pmid = {19800450}, issn = {1879-1883}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Gamma Rays ; Humans ; Middle Aged ; Radionuclide Imaging ; }, abstract = {BACKGROUND: We sought to determine the number of patients with known breast cancer who were found to have an additional, mammographically occult lesion detected on breast-specific gamma imaging (BSGI).

METHODS: An institutional review board-approved review of all patients who underwent BSGI at Beth Israel Medical Center from 2006 to 2008 was performed.

RESULTS: A total of 82 patients underwent BSGI for newly diagnosed breast cancer. Of these, 18 had an additional abnormality, and 17 were biopsied. There were 4 cases of invasive ductal carcinoma, 1 invasive lobular carcinoma, 1 ductal carcinoma in situ, 1 lobular carcinoma in situ, 2 papillomas, and 8 benign biopsies. One patient proceeded directly to mastectomy and an area of ductal carcinoma in situ was found, corresponding to the BSGI.

CONCLUSIONS: In our study group, 22% of patients had a surgical change in management based on BSGI findings. BSGI detected additional carcinoma in 9%. BSGI plays an important role in the clinical management of patients with known breast cancer.}, } @article {pmid19790246, year = {2010}, author = {Facina, G and Lopes-Costa, PV and Dos Santos, AR and De Vasconcelos-Valença, RJ and Pinho-Sobral, AL and Ferreira-Filho, CP and Alencar, AP and Gebrim, LH and Da Silva, BB}, title = {Immunohistochemical expression of E-cadherin in sclerosing adenosis, ductal carcinoma in situ and invasive ductal carcinoma of the breast.}, journal = {Diagnostic cytopathology}, volume = {38}, number = {4}, pages = {235-238}, doi = {10.1002/dc.21181}, pmid = {19790246}, issn = {1097-0339}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; Breast Neoplasms/*metabolism/*pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Female ; Fibrocystic Breast Disease/*metabolism/*pathology ; Humans ; Immunohistochemistry ; Middle Aged ; Sclerosis ; }, abstract = {E-cadherin (EC) is an important glycoprotein cell-adhesion molecule that appears to play a significant role in the progression of breast lesions. The objective of this study was to evaluate EC expression in sclerosing adenosis, ductal carcinoma in situ and invasive ductal carcinoma. Samples of breast lesions from 44 women were used in this study, comprising cases of sclerosing adenosis (n = 11), ductal carcinoma in situ (DCIS) (n = 10) and invasive ductal carcinoma (n = 23). Immunohistochemical evaluation of EC expression was assessed semiquantitatively and considered negative (<10% of cells with stained cytoplasmic membranes), positive+ (10-50% of cells stained) or positive++ (> 50% of cells stained). Fisher's exact test was used to compare the distribution of staining intensity in the lesions (P< 0.05). There was a progressive loss of EC expression from benign to malignant lesions. This difference was statistically significant when sclerosing adenosis was compared with DCIS (P < 0.0002), when sclerosing adenosis was compared with invasive ductal carcinoma (P < 0.008) and when DCIS was compared with invasive ductal carcinoma (P < 0.007). The present findings point to a significant association between reduced EC expression and the progression and aggressivity of breast lesions. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc.}, } @article {pmid19789948, year = {2013}, author = {Yamashita, M and Ogawa, T and Hanamura, N and Kashikura, Y and Mitsui, T and Zhang, X and Fujii, K and Shiraishi, T}, title = {An uncommon case of T1b breast cancer with diabetic mastopathy in type II diabetes mellitus.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {20}, number = {1}, pages = {92-96}, doi = {10.1007/s12282-009-0172-2}, pmid = {19789948}, issn = {1880-4233}, mesh = {Biopsy, Large-Core Needle ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Calcinosis ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Diabetes Mellitus, Type 2/*complications/drug therapy ; Female ; Fibrocystic Breast Disease/diagnosis/*etiology/pathology ; Humans ; Magnetic Resonance Imaging, Interventional ; Middle Aged ; Radiography ; Ultrasonography, Mammary ; }, abstract = {A 64-year-old postmenopausal female had been treated with insulin therapy for type 2 diabetes mellitus for 18 years, but her diabetes mellitus was not well controlled and she developed retinopathy. Her screening mammography showed abnormal findings, and thus she consulted a hospital. A physical examination showed her mammary glands to be hard on both sides and no palpable mass was observed. Mammography revealed an amorphous calcification in the middle outer portion of the left breast. Ultrasonography showed an irregular hypoechoic mass measuring about 11 mm in size in the upper outer portion of the left breast. Although a core-needle biopsy specimen of the hypoechoic mass showed hyalinizing fibrosis without any evidence of malignancy, a stereotactic guided vacuum-assisted biopsy was performed because magnetic resonance imaging revealed an enhanced area in the region of the amorphous calcification that could not be distinguished from breast cancer. The histological findings indicated noninvasive ductal carcinoma, and therefore a quardrantectomy with a sentinel lymph node biopsy was performed. The pathological diagnosis was invasive ductal carcinoma (0.7 × 0.3 cm) with a predominant intraductal component accompanying diabetic mastopathy. The sentinel lymph nodes demonstrated no metastasis. The surgical margin was positive for carcinoma and the patient later underwent a mastectomy. No malignant cells were observed in the specimen. The patient has so far experienced no recurrence after surgery.}, } @article {pmid19789946, year = {2010}, author = {Chaiwun, B and Nakrungsee, S and Sukhamwang, N and Srisukho, S}, title = {A study of high-nuclear-grade breast cancer in Thailand: subclassification and correlation with prognostic factors and immunohistochemical study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {17}, number = {1}, pages = {35-41}, doi = {10.1007/s12282-009-0174-0}, pmid = {19789946}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*classification/epidemiology/metabolism ; Carcinoma, Ductal, Breast/*classification/epidemiology/metabolism ; Carcinoma, Lobular/*classification/epidemiology/metabolism ; Carcinoma, Medullary/*classification/epidemiology/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Incidence ; Lymph Nodes/metabolism/pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; Thailand/epidemiology ; Treatment Outcome ; }, abstract = {OBJECTIVES: To classify high-nuclear-grade breast cancer (BC) into typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC), and luminal A, luminal B, and HER2, and to correlate these tumors with other prognostic factors.

MATERIALS AND METHODS: A retrospective study reviewing high-nuclear-grade BCs. The patients' age, histologic types, various histologic features, axillary lymph node (ALN) status, and results of immunohistochemical (IHC) study were recorded and analyzed.

RESULTS: One-hundred and eighty-one cases of high-nuclear-grade BCs were reviewed and categorized into IDC, NOS (140, 77.3%), TMC (1, 0.6%), AMC (21, 11.6%), and others (19, 10.5%). The median age was younger in AMC than in NMC patients. NMC patients had a higher incidence of LVI and ALN metastasis with involvement of more than four lymph nodes (p = 0.006) whereas AMC patients had a higher mitotic index. Forty-six (35.9%) cases were triple-negative (TN), including 1 (100%), 7 (53.9%) and 38 (33.3%) cases of TMC, AMC, and NMC, respectively. AMC had a significantly lower number of node metastases (p = 0.006) than NMC; whereas TN had higher MI (p = 0.001) than non-TN. The non-TN group was subclassified into luminal A, luminal B, and HER2. Of these, TN and luminal B occurred at younger age (p = 0.01) whereas TN and luminal A had a higher mitotic count. TN had lower incidence of LNM including higher number of LNM.

CONCLUSION: Overall, AMC-TN group showed a basal-like prognostic factor expression. NMC may be separated into TN and non-TN, with possibly different behavior. These sub-groupings should continue to be used. Interestingly, luminal A in our study tended to correlate with poor prognostic factors, thus, luminal A with high nuclear grade may not be representative of the usual luminal group profiles.}, } @article {pmid19785482, year = {2009}, author = {Mikulincer, M and Shaver, PR and Sapir-Lavid, Y and Avihou-Kanza, N}, title = {What's inside the minds of securely and insecurely attached people? The secure-base script and its associations with attachment-style dimensions.}, journal = {Journal of personality and social psychology}, volume = {97}, number = {4}, pages = {615-633}, doi = {10.1037/a0015649}, pmid = {19785482}, issn = {0022-3514}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Anxiety Disorders/complications/psychology ; Cognition ; Dreams/psychology ; Female ; Humans ; Israel ; Judgment ; Male ; Middle Aged ; *Object Attachment ; Personality Disorders/complications/psychology ; *Social Behavior ; Social Support ; Stress, Psychological/complications/psychology ; Students/psychology ; Task Performance and Analysis ; Young Adult ; }, abstract = {In 8 studies the authors explored the procedural knowledge (secure-base script; H. S. Waters & E. Waters, 2006) associated with secure attachment (i.e., low scores on attachment anxiety and avoidance). The studies assessed the accessibility, richness, and automaticity of the secure-base script and the extent to which it guided the processing of attachment-relevant information. Secure attachment (lower scores on anxiety and avoidance) was associated with greater secure-base "scriptedness" of attachment narratives, greater accessibility of the secure-base script in narratives and dreams about distressing experiences, deeper processing of script-relevant information, and faster and more confident script-relevant judgments. In addition, secure participants' tendency to process secure-base information more deeply was evident even 5 days after being exposed to it and was impervious to the depletion of cognitive resources, indicating automatic processing. The discussion focuses on implications of the findings for understanding the cognitive bases of secure people's affect-regulation strategies and behavior in social relationships.}, } @article {pmid19783719, year = {2009}, author = {Chang, H and Mohabir, N and Done, S and Hamel, PA}, title = {Loss of ALX4 expression in epithelial cells and adjacent stromal cells in breast cancer.}, journal = {Journal of clinical pathology}, volume = {62}, number = {10}, pages = {908-914}, doi = {10.1136/jcp.2009.067298}, pmid = {19783719}, issn = {1472-4146}, mesh = {Animals ; Breast/cytology/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/metabolism ; Female ; Homeodomain Proteins/metabolism ; Humans ; Mammary Glands, Animal/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasm Proteins/metabolism ; Species Specificity ; Stromal Cells/metabolism ; Tissue Array Analysis/methods ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.

AIMS: To begin to define the role of ALX4 in the human breast and in breast cancer, the expression pattern of ALX4 in the normal human breast and changes in expression in breast cancer were determined.

METHODS: Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using alpha-ALX4 antibodies and markers of specific mammary cell types. ALX4 expression in breast cancer was then determined by immunohistochemistry on tumour sections that also harboured regions of normal breast tissue. Using criteria that required ALX4 staining in both stromal and epithelial cells, changes in ALX4 expression in tumours on a tissue microarray were determined.

RESULTS: ALX4 was expressed in both stromal and luminal epithelial cells in the human breast. Scoring tissue sections of duct carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) that also harboured regions of normal breast tissue, a loss of ALX4 (p<0.001) in stromal and epithelial cells in breast tumours was observed. Analysis of ALX4 expression in 123 sections on a tissue microarray confirmed a highly significant loss (p<0.001) of ALX4 in breast cancer in the tumours themselves and in adjacent stromal cells.

CONCLUSIONS: These data show a distinct pattern of expression of ALX4 in the human breast relative to the murine mammary gland. Furthermore, characterisation of ALX4 in breast cancer showed that loss of ALX4 in tumours and the surrounding untransformed stroma is a basic characteristic of DCIS and IDC.}, } @article {pmid19781189, year = {2009}, author = {Lü, XQ and Suo, Z and Ma, CL and Xu, KJ and Liu, YS and Li, HX}, title = {[Quantity and distribution of CD44+/CD24- cells in breast cancer tissue and the cell lines].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {7}, pages = {441-444}, pmid = {19781189}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/classification/metabolism/*pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/classification/metabolism/*pathology ; Cell Line, Tumor ; Female ; Humans ; Hyaluronan Receptors/*metabolism ; Lymphatic Metastasis ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Trefoil Factor-1 ; Tumor Suppressor Proteins/metabolism ; }, abstract = {OBJECTIVE: To study the distribution and quantity of CD44+/CD24- cells in breast cancer tissue and the cell lines, and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma.

METHODS: The expression of CD44/CD24, estrogen receptor, progesterone receptor, HER2, human estrogen-induced protein PS2, bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining. The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) was also examined.

RESULTS: The quantity and distribution of CD44+/CD24- cells varied greatly and no specific patterns were identified. The percentage of CD44+/CD24- in breast cancer was 65%. The amount of CD44+/CD24- cells did not correlate with the age of patients, lymph node metastasis, tumor size, molecular subtypes and expression of various breast cancer markers in breast carcinoma. The proportion of CD44+/CD24- cells in MCF-7, MDA-MB-468, and MDA-MB-231 cell lines was <1%, 5% and >80%, respectively.

CONCLUSIONS: CD44+/CD24- cells are demonstrated in certain breast cancer tissues and cell lines. However, there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer.}, } @article {pmid19763516, year = {2009}, author = {Marsden, CG and Wright, MJ and Pochampally, R and Rowan, BG}, title = {Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {590}, number = {}, pages = {363-375}, doi = {10.1007/978-1-60327-378-7_23}, pmid = {19763516}, issn = {1940-6029}, mesh = {Animals ; Biopsy ; Breast Neoplasms/*pathology/physiopathology ; Female ; Hormones/*physiology ; Humans ; Immunohistochemistry ; Mice ; Neoplastic Stem Cells/*pathology ; }, abstract = {In recent years, evidence has emerged supporting the hypothesis that cancer is a stem cell disease. The cancer stem cell field was led by the discovery of leukemia stem cells (Tan, B.T., Park, C.Y., Ailles, L.E., and Weissman, I.L. (2006) The cancer stem cell hypothesis: a work in progress. Laboratory Investigation. 86, 1203-1207), and within the past few years cancer stem cells have been isolated from a number of solid tumor including those of breast and brain cancer among others (Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison, S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983-3988; Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003) Identification of a Cancer Stem Cell in Human Brain Tumors. Cancer Research. 63, 5821-5828). Cancer stem cells exhibit far different properties than established cells lines such as relative quiescence, multidrug resistance, and multipotency (Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H.M., Jones, D.L., Visvader, J., Weissman, I.L., and Wahl, G.M. (2006) Cancer Stem Cells-Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Research. 66, 9339-9344). In addition, our laboratory has demonstrated that breast cancer stem cells exhibit a strong metastatic phenotype when passaged in mice. Since stem cells exhibit these somewhat unique properties, it will be important for endocrinologists to evaluate hormonal action in these precursor cells for a more thorough understanding of cancer biology and development of more effective treatment modalities. A relatively easy and low cost method was developed to isolate breast cancer stem cells from primary needle biopsies taken from patients diagnosed with primary invasive ductal carcinoma during the routine care of patients with consent and IRB approval. Fresh needle biopsies (2-3 biopsies at 2 cm in length) were enzymatically dissociated in a collagenase (300 U/ml)/hyaluronidase (100 U/ml) solution followed by sequential filtration. Single cell suspensions were cultured on ultra low attachment plastic flasks in defined medium and formed non-adherent tumorspheres. The tumorspheres exhibited surface marker expression of CD44(+)/CD24(low/-)/ESA(+), previously defined as a "breast cancer stem cell" phenotype by Al Hajj et al. (Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison, S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast cancer cells.}, } @article {pmid19760610, year = {2009}, author = {Wang, C and Iakovlev, VV and Wong, V and Leung, S and Warren, K and Iakovleva, G and Arneson, NC and Pintilie, M and Miller, N and Youngson, B and McCready, DR and Done, SJ}, title = {Genomic alterations in primary breast cancers compared with their sentinel and more distal lymph node metastases: an aCGH study.}, journal = {Genes, chromosomes & cancer}, volume = {48}, number = {12}, pages = {1091-1101}, doi = {10.1002/gcc.20711}, pmid = {19760610}, issn = {1098-2264}, support = {STP-53912//Canadian Institutes of Health Research/Canada ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; Chromosomes, Human, Pair 17/genetics ; *Comparative Genomic Hybridization ; Female ; Genome, Human ; Humans ; Immunoenzyme Techniques ; Lymph Nodes ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Prognosis ; Sentinel Lymph Node Biopsy ; }, abstract = {Metastatic potential of breast cancer may be associated with specific genomic alterations and the earliest metastases are likely to be found in the sentinel lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we compared the genomes of primary breast invasive duct carcinomas (IDCs), their sentinel and more distal lymph node metastases, and IDCs without nodal metastasis. Thirty-three samples from 22 patients with IDC were subjected to aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs associated with SLN metastases out of which 7 had paired samples of metastases, and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs from 4 patients. aCGH data were analyzed by correlation of genomic profiles, cluster analysis, segmentation, and peak identification. Quantitative real-time PCR was used for data validation. We observed high genomic similarity between primary tumors and their nodal metastases as well as between metastases to the sentinel and distal lymph nodes. Several recurrent alterations were detected preferentially in IDC associated with SLN metastases compared to IDCs without metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was associated with presence of sentinel or distal lymph node metastases; larger tumor size and higher histological grade. In our samples, there were genomic events associated with metastatic progression, which could be detected in both primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for further testing as a predictor of nodal metastasis.}, } @article {pmid19760587, year = {2009}, author = {Lü, X and Li, H and Xu, K and Nesland, JM and Suo, Z}, title = {MUC-1-/ESA+ progenitor cells in normal, benign and malignant human breast epithelial cells.}, journal = {Histology and histopathology}, volume = {24}, number = {11}, pages = {1381-1390}, doi = {10.14670/HH-24.1381}, pmid = {19760587}, issn = {1699-5848}, mesh = {Breast/cytology/metabolism ; Breast Neoplasms/metabolism/*pathology ; Epithelial Cells/*metabolism ; Female ; Fibrocystic Breast Disease/metabolism ; Humans ; Immunohistochemistry ; Membrane Proteins/*metabolism ; Mucin-1/*metabolism ; Stem Cells/*cytology ; }, abstract = {The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer cell lines MCF-7 and MDA-MB-468. In normal breast tissues MUC-1-/ESA+ cells were mainly found in the suprabasal layer, but under the apical surface of the duct/alveolus. In the hyperplastic areas of fibrocystic disease, the number of this subpopulation of cells was higher than that in hypoplastic areas and in fibroadenomas. In invasive ductal carcinoma, the MMUC-1-/ESA+ cells were heterogeneously present in different carcinoma nests. In the MCF-7 cell line most cells were MUC-1-/ESA+, and in the MDA-MB-468 cell line MUC-1-/ESA+ cells and MUC-1-/ESA+ cells were almost equal. Our results show that the MUC-1-/ESA+ subpopulation increases in fibrocystic disease within the hyperplastic areas, and varies in benign and malignant breast tumours, indicating that breast carcinogenesis may develop from malignant changes of normal MUC-1-/ESA+ cells.}, } @article {pmid19755823, year = {2009}, author = {Tanigawa, T and Miyamoto, Y and Abe, M and Hasuo, T and Doiguchi, M and Sakamoto, F}, title = {[A case of inflammatory carcinoma, well-controlled by chemotherapy, especially, vinorelbine, S-1 and trastuzumab].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {9}, pages = {1515-1518}, pmid = {19755823}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma/drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Cyclophosphamide/administration & dosage ; Docetaxel ; Drug Administration Schedule ; Drug Combinations ; Female ; Humans ; Inflammation ; Middle Aged ; Oxonic Acid/administration & dosage ; Skin Neoplasms/drug therapy ; Taxoids/administration & dosage ; Tegafur/administration & dosage ; Trastuzumab ; Vinblastine/administration & dosage/analogs & derivatives ; Vinorelbine ; }, abstract = {We experienced a case of inflammatory carcinoma, which has been well controlled by chemotherapy, especially, vinorelbine, S-1 and trastuzumab. A 54-year-old woman was diagnosed as inflammatory carcinoma with T4d, N3c, M0 in Stage III c. The lesion was diagnosed as invasive ductal carcinoma, scirrhous, ER(-), PgR(-), HER2(3+) by core needle biopsy, The skin lesion was diagnosed as dermal lymphatic carcinomatosis by skin biopsy. The following chemotherapy was performed: FEC(5-FU 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2) followed by docetaxel(DOC 70 mg/m/2), every 3 weeks, each 6 times; after that, sequentially, vinorelbine (25 mg/m2)+trastuzumab (2 mg/kg every week), UFT(300 mg, daily)+cyclophosphamide (100 mg 2 weeks on, 1 week off)+trastuzumab (continued) and S-1 (120 mg/body 4 weeks on, 2 weeks off)+trastuzumab (continued). The patient has been well controlled by the chemotherapy with good QOL. Especially vinorelbine, S-1, and trastuzumab contributed to the disappearance of skin lesion.}, } @article {pmid19751508, year = {2009}, author = {Prasad, CP and Rath, G and Mathur, S and Bhatnagar, D and Parshad, R and Ralhan, R}, title = {Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {325}, pmid = {19751508}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*metabolism ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3/*metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Middle Aged ; Signal Transduction ; Snail Family Transcription Factors ; Transcription Factors/*metabolism ; Wnt1 Protein/metabolism ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.

METHODS: In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3beta in IDCs of breast.

RESULTS: Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.

CONCLUSION: The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3beta with beta-catenin in implementing EMT in these cells.}, } @article {pmid19749460, year = {2009}, author = {Gupta, S and Joshi, K and Wig, JD and Arora, SK}, title = {High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.}, journal = {Indian journal of cancer}, volume = {46}, number = {4}, pages = {303-310}, doi = {10.4103/0019-509X.55550}, pmid = {19749460}, issn = {1998-4774}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; *Genes, Wilms Tumor ; Humans ; Insulin-Like Growth Factor II/biosynthesis ; Loss of Heterozygosity ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptor, IGF Type 1/biosynthesis ; Transforming Growth Factor beta1/biosynthesis ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {BACKGROUND: The product of Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression.

METHODS: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-beta1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma.

RESULTS: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-beta1, VEGF expression and IMD scores in infiltrating carcinoma.

CONCLUSIONS: The current study indicates that the high frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.}, } @article {pmid19745684, year = {2009}, author = {Lahey, T and Shah, R and Gittzus, J and Schwartzman, J and Kirkland, K}, title = {Infectious diseases consultation lowers mortality from Staphylococcus aureus bacteremia.}, journal = {Medicine}, volume = {88}, number = {5}, pages = {263-267}, pmid = {19745684}, issn = {1536-5964}, support = {K08 AI069915/AI/NIAID NIH HHS/United States ; K08 AI069915-04/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteremia/epidemiology/*mortality/prevention & control ; Central Nervous System Diseases/microbiology/mortality ; Endocarditis/microbiology/mortality ; Female ; Hospital Mortality ; Humans ; Lebanon/epidemiology ; Male ; Middle Aged ; Osteomyelitis/microbiology/mortality ; Prevalence ; *Referral and Consultation ; Retrospective Studies ; Staphylococcal Infections/epidemiology/*mortality/prevention & control ; Staphylococcus aureus/*isolation & purification ; Survival Analysis ; }, abstract = {Staphylococcus aureus bacteremia (SAB) is a lethal and increasingly common infection in hospitalized patients. We assessed the impact of infectious diseases consultation (IDC) on clinical management and hospital mortality of SAB in 240 hospitalized patients in a retrospective cohort study. Patients who received IDC were older than those who did not (57.9 vs. 51.7 yr; p = 0.05), and were more likely to have a health care-associated infection (63% vs. 45%; p < 0.01). In patients who received IDC, there was a higher prevalence of severe complications of SAB such as central nervous system involvement (5% vs. 0%, p = 0.01), endocarditis (20% vs. 2%; p < 0.01), or osteomyelitis (15.6% vs. 3.4%; p < 0.01). Patients who received IDC had closer blood culture follow-up and better antibiotic selection, and were more likely to have pus or prosthetic material removed. Hospital mortality from SAB was lower in patients who received IDC than in those who did not (13.9% vs. 23.7%; p = 0.05). In multivariate survival analysis, IDC was associated with substantially lower hazard of hospital mortality during SAB (hazard 0.46; p = 0.03). This mortality benefit accrued predominantly in patients with methicillin-resistant SAB (hazard 0.3; p < 0.01), and in patients who did not require ICU admission (hazard 0.15; p = 0.01). In conclusion, IDC is associated with reduced mortality in patients with staphylococcal bacteremia.}, } @article {pmid19744374, year = {2009}, author = {Helali, F}, title = {Using ergonomics checkpoints to support a participatory ergonomics intervention in an industrially developing country (IDC)--a case study.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {15}, number = {3}, pages = {325-337}, doi = {10.1080/10803548.2009.11076811}, pmid = {19744374}, issn = {1080-3548}, mesh = {Decision Making, Organizational ; *Developing Countries ; *Ergonomics ; Humans ; *Industry ; Inservice Training ; Iran ; Needs Assessment ; *Occupational Health ; Organizational Case Studies ; *Workplace ; }, abstract = {To achieve ergonomics awareness in 3 subsidiary companies, an intervention team was formed. The aims of this study were to implement basic ergonomics through a participatory ergonomics intervention process that can support a continuous learning process and lead to an improvement in health and safety as well as in the work systems in the organization. The findings of this study (i.e., method, continuous learning and integration) were key to making the participatory ergonomics intervention successful. Furthermore, 4 issues of the ergonomics checkpoints (i.e., work schedules, work tasks, healthy work organization and learning) for assessing the work system were found suitable for both changing work schedules and for improving the work system. This paper describes the result of this project and also the experiences gained and the conclusions reached from using the International Labour Office's ergonomics checkpoints in the industries of industrially developing country.}, } @article {pmid19740438, year = {2009}, author = {Bloise, E and Couto, HL and Massai, L and Ciarmela, P and Mencarelli, M and Borges, LE and Muscettola, M and Grasso, G and Amaral, VF and Cassali, GD and Petraglia, F and Reis, FM}, title = {Differential expression of follistatin and FLRG in human breast proliferative disorders.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {320}, pmid = {19740438}, issn = {1471-2407}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/genetics/metabolism ; Female ; Follistatin/*genetics/metabolism ; Follistatin-Related Proteins/*genetics/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Protein Transport ; }, abstract = {BACKGROUND: Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG) bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases.

METHODS: Paraffin embedded specimens of normal breast (NB - n = 8); florid hyperplasia without atypia (FH - n = 17); fibroadenoma (FIB - n = 17); ductal carcinoma in situ (DCIS - n = 10) and infiltrating ductal carcinoma (IDC - n = 15) were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively.

RESULTS: Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed.

CONCLUSION: The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the present findings indicate that an increased FST and FLRG expression in breast proliferative diseases might counteract the anti-proliferative effects of activin in human breast cancer.}, } @article {pmid19740355, year = {2009}, author = {Kamdar, A and Yahya, A and Thangaraj, L}, title = {Retrospective observational study of the incidence of short-term indwelling urinary catheters in elderly patients with neck of femur fractures.}, journal = {Geriatrics & gerontology international}, volume = {9}, number = {2}, pages = {131-134}, doi = {10.1111/j.1447-0594.2008.00490.x}, pmid = {19740355}, issn = {1447-0594}, mesh = {Aged ; Aged, 80 and over ; Catheters, Indwelling/adverse effects/*statistics & numerical data ; Device Removal/adverse effects ; England/epidemiology ; Female ; Femoral Fractures/complications/*epidemiology ; Hospitals/statistics & numerical data ; Humans ; Incidence ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Urinary Catheterization/adverse effects/*statistics & numerical data ; Urinary Incontinence/complications/*epidemiology ; Urinary Retention/complications/*epidemiology ; }, abstract = {BACKGROUND: 15-25% of general hospital admissions tend to involve patients that have had a short-term indwelling urinary catheter (IDC) inserted some time during their stay. There is little data on the specific incidence and complications of short-term urinary catheterization in elderly patients with neck of femur fractures.

METHODS: Data was collected from the notes of 50 patients at Hemel Hempstead General Hospital with neck of femur fractures retrospectively from 31 August 2007. Specific information on patient demographics, premorbid status, record and reason for urethral catheterization, place of insertion, gentamicin cover pre- and post-removal of IDC, residual volumes, duration of catheter insertion, catheter clamping prior to removal of IDC, urinary tract infection with IDC, post-IDC removal newly incontinent/in retention were collated from patient notes. Patients with prior chronic catheterization were excluded from the study.

RESULTS: 78% of the patients had an IDC insertion (95% confidence interval, 64-88.4%). Most of the catheters were inserted on the ward (75%) with the rest being inserted mostly in theatre and recovery. Only approximately one-third of the sample that had IDC inserted had residual volume documented in the notes. Of these patients, the majority had residual volume above 300 mL. The main reasons for IDC insertion were urinary retention (50%), incontinence (30.8%) and fluid monitoring (11.5%). Of the patients, 31.4% had documented urinary tract infection as a result of IDC insertion.

CONCLUSION: This study revealed a higher incidence of short-term IDC insertion (approximately 75%) in elderly patients with neck of femur fractures in comparison to general hospital admissions of 15-25%. There is a role for more effective documentation in patient notes on the reasons behind urinary IDC insertion and increased clinical vigilance in preventing unnecessary catheterizations.}, } @article {pmid19729831, year = {2009}, author = {Yoon, NK and Seligson, DB and Chia, D and Elshimali, Y and Sulur, G and Li, A and Horvath, S and Maresh, E and Mah, V and Bose, S and Bonavida, B and Goodglick, L}, title = {Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {5}, number = {4}, pages = {215-224}, pmid = {19729831}, issn = {1875-8592}, support = {CA-86366/CA/NCI NIH HHS/United States ; U24 CA086366/CA/NCI NIH HHS/United States ; U24 CA086366-06/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; P30 CA016042-29/CA/NCI NIH HHS/United States ; 2 P30 CA16042-29/CA/NCI NIH HHS/United States ; }, mesh = {14-3-3 Proteins ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Exonucleases/*biosynthesis/genetics ; Exoribonucleases ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Prognosis ; Survival Analysis ; }, abstract = {The protein 14-3-3sigma is involved in the regulation of cellular processes such as apoptosis, cell cycle progression and proliferation. Disruption of protein expression has been implicated in a number of malignancies. Here we examine the expression pattern of 14-3-3sigma in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3sigma protein expression and localization using immunohistochemical staining on a high-density tissue microarray consisting of 157 invasive breast cancer patients. Statistical analyses were used to assess the correlation of 14-3-3sigma expression with clinico-pathological parameters and patient outcome. We observed a statistically significant increase in 14-3-3sigma protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3sigma tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3sigma predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3sigma expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3sigma expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3sigma in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3sigma protein expression with breast cancer survival.}, } @article {pmid19725664, year = {2009}, author = {Weber, JK and Rey, CA and Neuefeind, J and Benmore, CJ}, title = {Acoustic levitator for structure measurements on low temperature liquid droplets.}, journal = {The Review of scientific instruments}, volume = {80}, number = {8}, pages = {083904}, doi = {10.1063/1.3196177}, pmid = {19725664}, issn = {1089-7623}, mesh = {Acoustics/*instrumentation ; Cerium ; *Cold Temperature ; Electric Power Supplies ; Equipment Design ; Extreme Cold Weather ; Gases ; Heating/instrumentation ; Optics and Photonics/instrumentation ; Periodicity ; Polystyrenes ; Pressure ; Time Factors ; Transducers ; Video Recording/instrumentation ; Water ; X-Rays ; }, abstract = {A single-axis acoustic levitator was constructed and used to levitate liquid and solid drops of 1-3 mm in diameter at temperatures in the range -40 to +40 degrees C. The levitator comprised (i) two acoustic transducers mounted on a rigid vertical support that was bolted to an optical breadboard, (ii) an acoustic power supply that controlled acoustic intensity, relative phase of the drive to the transducers, and could modulate the acoustic forces at frequencies up to 1 kHz, (iii) a video camera, and (iv) a system for providing a stream of controlled temperature gas flow over the sample. The acoustic transducers were operated at their resonant frequency of approximately 22 kHz and could produce sound pressure levels of up to 160 dB. The force applied by the acoustic field could be modulated to excite oscillations in the sample. Sample temperature was controlled using a modified Cryostream Plus and measured using thermocouples and an infrared thermal imager. The levitator was installed at x-ray beamline 11 ID-C at the Advanced Photon Source and used to investigate the structure of supercooled liquids.}, } @article {pmid19722158, year = {2009}, author = {Safwat, MD and Habib, F and Elayat, A and Oweiss, N and Reffat, S and Algaidi, S}, title = {Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast.}, journal = {Folia morphologica}, volume = {68}, number = {3}, pages = {144-155}, pmid = {19722158}, issn = {0015-5659}, mesh = {Adult ; Antigens, CD/analysis/metabolism ; Antigens, CD34/analysis/metabolism ; Biomarkers, Tumor/analysis/*metabolism ; Blood Vessels/metabolism/pathology ; Breast Neoplasms/*blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/*metabolism/pathology ; Disease Progression ; Endoglin ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/*metabolism/pathology/physiopathology ; Predictive Value of Tests ; Receptors, Cell Surface/analysis/metabolism ; Sensitivity and Specificity ; Vascular Endothelial Growth Factor A/analysis/metabolism ; }, abstract = {Breast cancer is the leading cause of cancer deaths among women. Results from experimental studies suggest that tumour progression and metastasis in breast cancer are angiogenesis dependant. The College of American Pathologists has stated that further study of quantification of tumour angiogenesis is still required to demonstrate its prognostic value in breast cancer. In this study, not only the microvascular density (MVD), but also the vascular area ratio (VAR), and the vascular count in different grades of invasive ductal breast carcinoma were assessed using a pan-endothelial marker, CD34, and monoclonal antibody to CD105, by employing computer assisted morphometric measurements. In addition, quantitative expression of vascular endothelial growth factor (VEGF) was detected. Correlation of the vascular parameters and VEGF expression with the different grades of invasive ductal breast carcinoma was clarified. Immunohistochemical staining for the CD105, CD34, and VEGF antibodies were performed in 25 patients with invasive ductal carcinoma in King Fahd Hospital, Saudi Arabia. Normal breast tissue samples comprised 15 specimens detected at the safety margin of the malignant breast cases were collected. Positive CD34 stained blood-vessel endothelial cells were observed in all normal breast tissues. In contrast, CD105 and VEGF expression were not expressed in the normal breast ducts and lobules. Widespread staining for CD34, to a lesser extent CD105, and VEGF expression were seen in all tumour specimens with different grades. Significant differences in the vascular parameters, stained with antiCD34, were observed between normal breast tissues and invasive ductal carcinoma. In addition, the vascular parameters stained with antiCD34 and antiCD105, and the percentage of VEGF expression in the three grades of invasive ductal carcinomas showed significant differences with positive correlations. In conclusion, MVD as well as VAR are considered to reflect the final result of the tumour angiogenesis cascade. In addition, VEGF expression was found to be a useful angiogenic marker. However, few cases were VEGF negatively stained. Thus, the expression of MVD, VAR, and to a lesser extent VEGF might be reference predictors for the biological behaviour and prognosis of breast carcinoma.}, } @article {pmid19720914, year = {2009}, author = {Jones, HA and Antonini, N and Hart, AA and Peterse, JL and Horiot, JC and Collin, F and Poortmans, PM and Oei, SB and Collette, L and Struikmans, H and Van den Bogaert, WF and Fourquet, A and Jager, JJ and Schinagl, DA and Wárlám-Rodenhuis, CC and Bartelink, H}, title = {Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {27}, number = {30}, pages = {4939-4947}, pmid = {19720914}, issn = {1527-7755}, support = {U10 CA011488/CA/NCI NIH HHS/United States ; 5U10-CA11488-38/CA/NCI NIH HHS/United States ; 5R10-CA11488-11/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Factors ; Aged ; Breast/pathology ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/prevention & control ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {PURPOSE: To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT).

PATIENTS AND METHODS: In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.

RESULTS: The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively.

CONCLUSION: Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.}, } @article {pmid19719774, year = {2009}, author = {Hasebe, T and Okada, N and Tamura, N and Houjoh, T and Akashi-Tanaka, S and Tsuda, H and Shibata, T and Sasajima, Y and Iwasaki, M and Kinoshita, T}, title = {p53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {100}, number = {11}, pages = {2101-2108}, doi = {10.1111/j.1349-7006.2009.01307.x}, pmid = {19719774}, issn = {1349-7006}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Female ; Fibroblasts/chemistry ; Genes, p53 ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Staging ; Stromal Cells/chemistry ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {The purpose of this study was to determine whether p53 protein expression in tumor stromal fibroblasts assessed immunohistochemically by the Allred score system is significantly associated with nodal metastasis by invasive ductal carcinoma (IDC), and significantly associated with the outcome of 1042 IDC patients according to adjuvant therapy status, UICC pTNM stage, and triple-negative IDC status, in multivariate analyses with well-known clinicopathological factors. The Allred scores for p53 expression in tumor stromal fibroblasts were significantly associated with the number of nodal metastases, and Allred scores of 4-8 for p53 in tumor stromal fibroblasts significantly increased the hazard rate for distant organ metastasis or for tumor death in the triple-negative IDC patients, and the UICC pTNM stage I, II, and III patients. The results indicated that p53 protein expression in tumor stromal fibroblasts is closely associated with the number of nodal metastases and the outcome of IDC patients.}, } @article {pmid19702365, year = {2009}, author = {Katz-Navon, T and Naveh, E and Stern, Z}, title = {Active learning: when is more better? The case of resident physicians' medical errors.}, journal = {The Journal of applied psychology}, volume = {94}, number = {5}, pages = {1200-1209}, doi = {10.1037/a0015979}, pmid = {19702365}, issn = {0021-9010}, mesh = {Adult ; Female ; Humans ; *Internship and Residency ; Israel ; Leadership ; Male ; Medical Errors/*prevention & control/statistics & numerical data ; *Organizational Culture ; *Problem-Based Learning ; Professional Role ; Regression Analysis ; *Safety Management ; }, abstract = {An active learning climate facilitates new knowledge acquisition by encouraging employees to ask questions, seek feedback, reflect on potential results, explore, and experiment. These activities, however, also increase a learner's chances of erring. In high-reliability organizations, any error is unacceptable and may well be life threatening. The authors use the example of resident physicians to suggest that by adjusting the conditions of priority of safety and managerial safety practices, organizations can balance these potentially conflicting activities. Participants in the study were 123 residents from 25 medical wards. Results demonstrated that the positive linear relationship between priority of safety and safety performance, demonstrated in earlier studies, existed only when the active learning climate was low. When the active learning climate was high, results demonstrated a U-shaped curvilinear relationship between priority of safety and number of errors. In addition, high managerial safety practices mitigated the number of errors as a result of the active learning climate.}, } @article {pmid19701678, year = {2010}, author = {Jara-Lazaro, AR and Thilagaratnam, S and Tan, PH}, title = {Breast cancer in Singapore: some perspectives.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {17}, number = {1}, pages = {23-28}, doi = {10.1007/s12282-009-0155-3}, pmid = {19701678}, issn = {1880-4233}, mesh = {Adult ; Age Distribution ; Biomedical Research ; Breast Neoplasms/diagnostic imaging/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*epidemiology/pathology ; Early Detection of Cancer ; Ethnicity ; Female ; Humans ; Incidence ; Mammography ; *Mass Screening ; Middle Aged ; National Health Programs ; Singapore/epidemiology ; }, abstract = {Breast cancer is the commonest malignancy among Singapore women, accounting for 29.7% of all female cancers, with an age-standardized rate of 54.9 per 100,000 per year. It has been the most frequent cancer in Singapore women for the last 30 years, with the highest rates previously reported in those aged between 45 and 49 years, but with a more recent observation of a change in peak age group to women in their late 50s. About 1,100 new cases are diagnosed annually and approximately 270 women die in Singapore each year from breast cancer. In the multiethnic population of Singapore, it has been noted that rising breast cancer incidence is consistent across all three ethnic groups (Chinese, Malays, and Indians). Singapore has among the highest breast cancer incidence in Asia. Possible explanations include rapid urbanization, improvement in socio-economic status, and adoption of a western lifestyle. Our experience with the Singapore breast screening pilot project (1994-1997) and the national breast-screening program (BreastScreen Singapore) has led to increased understanding of this disease in the country. Data from the pilot project showed that breast screening is just as effective in a predominantly Asian population as in the west. Early breast cancer accounted for most breast cancers detected, with pre-invasive ductal carcinoma in situ (DCIS) comprising 26% of all screen-detected cancers in the pilot study. In the currently on-going BreastScreen Singapore, DCIS forms >30% of all breast cancers among pre-menopausal women, a relatively high proportion probably accounted for partially by the greater participation of women aged between 40 and 49 years. Despite the ready availability of subsidized mammographic screening, there are still women in Singapore who present with locally advanced breast cancer. Clinical management of an increasing number of women with breast cancer embraces a multidisciplinary team-based approach, with regular discussions of therapeutic strategies at tumor boards. In order to improve breast cancer diagnostics and therapeutics in our country, it is important that there are continual breast cancer and breast disease-related educational activities for medical professionals engaged in diagnosing and managing breast cancer. The role of public education in raising awareness is also essential.}, } @article {pmid19700666, year = {2009}, author = {Anand, AR and Prasad, A and Bradley, RR and Deol, YS and Nagaraja, T and Ren, X and Terwilliger, EF and Ganju, RK}, title = {HIV-1 gp120-induced migration of dendritic cells is regulated by a novel kinase cascade involving Pyk2, p38 MAP kinase, and LSP1.}, journal = {Blood}, volume = {114}, number = {17}, pages = {3588-3600}, pmid = {19700666}, issn = {1528-0020}, support = {R01 HL087576/HL/NHLBI NIH HHS/United States ; HL087576/HL/NHLBI NIH HHS/United States ; }, mesh = {Blotting, Western ; *Cell Movement ; Chemotaxis ; Dendritic Cells/*metabolism ; Flow Cytometry ; Focal Adhesion Kinase 2/antagonists & inhibitors/genetics/*metabolism ; HIV Envelope Protein gp120/genetics/*metabolism ; Humans ; Microfilament Proteins/antagonists & inhibitors/genetics/*metabolism ; Phosphorylation/drug effects ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/pharmacology ; Receptors, CCR5/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tyrphostins/pharmacology ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {Targeting dendritic cell (DC) functions such as migration is a pivotal mechanism used by HIV-1 to disseminate within the host. The HIV-1 envelope protein is the most important of the virally encoded proteins that exploits the migratory capacity of DCs. In the present study, we elucidated the signaling machinery involved in migration of immature DCs (iDCs) in response to HIV-1 envelope protein. We observed that M-tropic HIV-1 glycoprotein 120 (gp120) induces phosphorylation of the nonreceptor tyrosine kinase, Pyk2. Inhibition of Pyk2 activity using a pharmacologic inhibitor, kinase-inactive Pyk2 mutant, and Pyk2-specific small interfering RNA blocked gp120-induced chemotaxis, confirming the role of Pyk2 in iDC migration. In addition, we also illustrated the importance of Pyk2 in iDC migration induced by virion-associated envelope protein, using aldithriol-2-inactivated M-tropic HIV-1 virus. Further analysis of the downstream signaling mechanisms involved in gp120-induced migration revealed that Pyk2 activates p38 mitogen-activated protein kinase, which in turn activates the F-actin-binding protein, leukocyte-specific protein 1, and enhances its association with actin. Taken together, our studies provide an insight into a novel gp120-mediated pathway that regulates DC chemotaxis and contributes to the dissemination of HIV-1 within an infected person.}, } @article {pmid19699526, year = {2009}, author = {van Stijn, CM and van den Broek, M and van de Weerd, R and Visser, M and Taşdelen, I and Tefsen, B and van Die, I}, title = {Regulation of expression and secretion of galectin-3 in human monocyte-derived dendritic cells.}, journal = {Molecular immunology}, volume = {46}, number = {16}, pages = {3292-3299}, doi = {10.1016/j.molimm.2009.07.026}, pmid = {19699526}, issn = {1872-9142}, mesh = {Animals ; Apoptosis/drug effects/physiology ; Cell Differentiation/drug effects/*physiology ; Cells, Cultured ; Dendritic Cells/cytology/immunology/*metabolism ; Galectin 3/*biosynthesis/immunology ; Gene Expression Regulation/drug effects/*physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology/metabolism/pharmacology ; Humans ; Interleukin-4/immunology/metabolism/pharmacology ; Monocytes/cytology/immunology/*metabolism ; Phosphatidylserines/genetics/immunology/metabolism ; RNA, Messenger/biosynthesis/immunology ; Schistosoma mansoni/immunology ; Schistosomiasis mansoni/immunology/metabolism ; Th2 Cells/immunology/metabolism ; }, abstract = {Galectin-3 (Gal-3) is a beta-galactoside binding lectin displaying both intracellular and extracellular immune functions. In Schistosoma mansoni infection, Gal-3 has been associated with the induction of a T helper 2 response. Whereas dendritic cells (DCs) play a pivotal role in the regulation of T cell differentiation, little is known about the regulation of Gal-3 expression in DCs. In this study we determined Gal-3 mRNA and protein levels during in vitro differentiation of human monocytes into immature DCs (iDCs), by culturing monocytes in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Gal-3 mRNA levels show a moderate, transient increase during iDC generation, accompanied by elevated cell-associated Gal-3 protein. Our data show that culturing monocytes with IL-4 alone strongly increases Gal-3 mRNA levels, whereas GM-CSF induces a low increase in Gal-3 mRNA. The combined data indicate that GM-CSF reduces IL-4 induced Gal-3 mRNA levels during the generation of iDC. Remarkably, stimulation of monocytes with GM-CSF results in secretion of significant amounts of Gal-3 in the medium, whereas iDCs do not release detectable amounts of Gal-3, indicating a suppressive role of IL-4 on GM-CSF induced Gal-3 secretion. Finally, our data demonstrate that all differentiated cell types tested show a significantly lower capacity to bind Gal-3 on the cell surface than monocytes. In conclusion, Gal-3 expression in iDCs is restricted, and Gal-3 protein is localized mainly intracellular, due to the opposite actions of IL-4 and GM-CSF. By these properties, the DCs may be protected against Gal-3 induced phosphatidylserine (PS) exposure and/or apoptosis.}, } @article {pmid19696299, year = {2009}, author = {Jansen, SA and Shimauchi, A and Zak, L and Fan, X and Wood, AM and Karczmar, GS and Newstead, GM}, title = {Kinetic curves of malignant lesions are not consistent across MRI systems: need for improved standardization of breast dynamic contrast-enhanced MRI acquisition.}, journal = {AJR. American journal of roentgenology}, volume = {193}, number = {3}, pages = {832-839}, pmid = {19696299}, issn = {1546-3141}, support = {P50 CA125183/CA/NCI NIH HHS/United States ; P50 CA125183-01/CA/NCI NIH HHS/United States ; }, mesh = {Biopsy ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Contrast Media/*pharmacokinetics ; Diagnosis, Differential ; Female ; Gadolinium DTPA/*pharmacokinetics ; Humans ; Kinetics ; Magnetic Resonance Imaging/*standards ; Middle Aged ; ROC Curve ; Retrospective Studies ; }, abstract = {OBJECTIVE: The purpose of this study was to compare MRI kinetic curve data acquired with three systems in the evaluation of malignant lesions of the breast.

MATERIALS AND METHODS: The cases of 601 patients with 682 breast lesions (185 benign, 497 malignant) were selected for review. The malignant lesions were classified as ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and other. The dynamic MRI protocol consisted of one unenhanced and three to seven contrast-enhanced images acquired with one of three imaging protocols and systems. An experienced radiologist analyzed the shapes of the kinetic curves according to the BI-RADS lexicon. Several quantitative kinetic parameters were calculated, and the kinetic parameters of malignant lesions were compared across the three systems.

RESULTS: Imaging protocol and system 1 were used to image 304 malignant lesions (185 IDC, 62 DCIS); imaging protocol and system 2, 107 lesions (72 IDC, 21 DCIS); and imaging protocol and system 3, 86 lesions (64 IDC, 17 DCIS). Compared with those visualized with imaging protocols and systems 1 and 2, IDC lesions visualized with imaging protocol and system 3 had significantly less initial enhancement, longer time to peak enhancement, and a slower washout rate (p < 0.004). Only 47% of IDC lesions imaged with imaging protocol and system 3 exhibited washout type curves, compared with 75% and 74% of those imaged with imaging protocols and systems 2 and 1, respectively. The diagnostic accuracy of kinetic analysis was lowest for imaging protocol and system 3, but the difference was not statistically significant.

CONCLUSION: The kinetic curve data on malignant lesions acquired with one system showed significantly lower initial contrast uptake and a different curve shape in comparison with data acquired with the other two systems. Differences in k-space sampling, T1 weighting, and magnetization transfer effects may be explanations for the difference.}, } @article {pmid19695680, year = {2009}, author = {Walter, O and Prasad, M and Lu, S and Quinlan, RM and Edmiston, KL and Khan, A}, title = {IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype.}, journal = {Human pathology}, volume = {40}, number = {11}, pages = {1528-1533}, doi = {10.1016/j.humpath.2009.05.005}, pmid = {19695680}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Phenotype ; RNA-Binding Proteins/*biosynthesis ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Retrospective Studies ; }, abstract = {IMP3, an oncofetal protein, is a member of the insulin-like growth factor-II (IGF-II) mRNA-binding protein family. Its relevance as a novel biomarker in lung, pancreatic, renal, and cervical adenocarcinoma was recently revealed. However, its role in breast carcinogenesis and tumor progression is not yet established. Basal-like carcinoma was initially identified by gene expression profiling. It accounts for 15% to 30% of all breast cancers. These tumors express basal epithelial markers including cytokeratin 5 but lack expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), therefore, are often referred to as triple negative breast cancer. They have been found to be associated with a worse overall and disease-free survival. In this retrospective study, we examined the IMP3 expression in invasive ductal carcinoma of the breast and correlated its expression with morphological and biologic prognostic factors. The study group comprised 138 cases of invasive ductal carcinoma retrieved from the surgical pathologic files for a 10-year period from 1997 to 2006. Survival data and clinical stage were available on all 138 patients. Tumor characteristics including size, grade, lymphovascular invasion, necrosis, lymph node metastasis, estrogen receptor, progesterone receptor, and HER2 status were obtained from pathologic reports. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue using mouse monoclonal antibody against IMP3 and CK5/6. Of the 138 breast cancer cases, IMP3 expression was seen in 45 (33%). Twenty-five of the IMP3+ cases were triple negative. We found significant correlation between IMP3 expression and higher grade (P = .001), necrosis (P< .0001) triple negative, and CK5/6 expression (P < .0001 for each). Cox multivariate analysis showed a hazard ratio of IMP3 expression at 3.14 (P = .05). IMP3 is a novel biomarker for triple negative (basal-like) invasive mammary carcinoma, and its expression is associated with a more aggressive phenotype and decreased overall survival.}, } @article {pmid19690768, year = {2009}, author = {Comănescu, M and Popescu, CF}, title = {BRCA1 expression in invasive breast carcinomas and clinicopathological correlations.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {50}, number = {3}, pages = {419-424}, pmid = {19690768}, issn = {1220-0522}, mesh = {Adult ; BRCA1 Protein/*metabolism ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {BRCA1-positive tumors characterize a heterogeneous group of breast cancers with a specific range of histopathological and immuno-histochemical features. We evaluated the relationship between morphological characteristics and immunohistochemical profile of 14 BRCA1-positive breast tumors from an initial study group of 40 breast tumors. Morphological parameters of all cases were studied on Hematoxylin-Eosin-stained sections and their immunophenotypic profile was assessed using antibodies against estrogen receptors (ER), progesteron receptors (PR), c-erbB2 oncoprotein (Her2/neu), BRCA1-protein, and the proliferative rate of the tumoral cells was assessed by Ki-67-proliferative index. All patients were females with an average age of 43.71-year-old. Fourteen out of the 40 tumors were BRCA1-positive. All breast carcinomas in this study were invasive. The most common histological type in our study was invasive ductal carcinoma. The majority of the tumors were high-grade G3. The examination of the lymph node found metastasis in eight cases. We found 11 cases of triple negative (ER, PR and Her2/neu), while the rest showed positivity for all these three markers. We observed a high-celullar proliferation index in all cases. The immunohistochemical study of BRCA1-protein is important to the study of the development and progression of the disease.}, } @article {pmid19690548, year = {2009}, author = {Ueno, H and Kosuge, T and Matsuyama, Y and Yamamoto, J and Nakao, A and Egawa, S and Doi, R and Monden, M and Hatori, T and Tanaka, M and Shimada, M and Kanemitsu, K}, title = {A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer.}, journal = {British journal of cancer}, volume = {101}, number = {6}, pages = {908-915}, pmid = {19690548}, issn = {1532-1827}, mesh = {Adult ; Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Deoxycytidine/adverse effects/*analogs & derivatives/therapeutic use ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/mortality/*therapy ; Survival Rate ; Gemcitabine ; }, abstract = {BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer.

METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles.

RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19).

CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.}, } @article {pmid19688132, year = {2008}, author = {Eo, WK}, title = {Breast cancer metastasis to the stomach resembling early gastric cancer.}, journal = {Cancer research and treatment}, volume = {40}, number = {4}, pages = {207-210}, pmid = {19688132}, issn = {1598-2998}, abstract = {Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast.}, } @article {pmid19679464, year = {2011}, author = {Tang, SW and Parker, H and Winterbottom, L and Hassell, K and Ellis, IO and Morgan, DA and Cheung, KL}, title = {Early primary breast cancer in the elderly - pattern of presentation and treatment.}, journal = {Surgical oncology}, volume = {20}, number = {1}, pages = {7-12}, doi = {10.1016/j.suronc.2009.07.004}, pmid = {19679464}, issn = {1879-3320}, mesh = {Aged ; Aged, 80 and over ; Attitude to Health ; Breast Neoplasms/pathology/psychology/*therapy ; Carcinoma, Ductal, Breast ; Chronic Disease/epidemiology ; Combined Modality Therapy/methods ; Comorbidity ; Decision Making ; Female ; Humans ; United Kingdom/epidemiology ; }, abstract = {INTRODUCTION: The incidence of primary breast cancer in elderly patients is increasing. However, little is known about their biological profile and most appropriate clinical management, as most studies have been conducted in the younger population. This study aimed to identify a profile of characteristics in elderly women with operable primary breast cancer and investigate the dynamics influencing the treatment decision-making process.

METHODS: A review of 268 consecutive female patients >70 years of age, diagnosed with early operable primary breast cancer (<5 cm) over a 30-month period at the Nottingham Breast Institute, was conducted. Age, co-morbidity, cancer characteristics, treatment offered and undertaken, and reason for patient choice were recorded and analysed.

RESULTS: The median age was 78 (range 70-100) years. In our study, 82% of the patients had one or more co-morbidities, with 34% of them having three or more co-morbidities. The commonest pathological diagnosis (from needle core biopsies) was invasive ductal carcinoma of no special type (76%) with histological grade 2 (64%). Majority of them were oestrogen receptor (ER)-positive (84%) and had a high histochemical (H)-score (83% with H-score >200). Most of the patients (60%) underwent primary surgical management, of which 45.4% received breast-conserving surgery. Among the patients who had breast-conserving surgery, 68% of them received adjuvant radiotherapy. When offered genuine choice in treatment options, most patients chose non-operative treatment. Patients who underwent non-operative treatment were on average seven years older and had significantly more co-morbidities than those who had surgery.

CONCLUSION: The elderly population evidently have demographic and cancer characteristics distinct from their younger counterparts, with less patients receiving surgical management. Further work is underway to correlate this with their clinical outcomes and to examine the factors behind the treatment decision-making process.}, } @article {pmid19675466, year = {2009}, author = {Lemaître, F and Seifert, L and Polin, D and Juge, J and Tourny-Chollet, C and Chollet, D}, title = {Apnea training effects on swimming coordination.}, journal = {Journal of strength and conditioning research}, volume = {23}, number = {6}, pages = {1909-1914}, doi = {10.1519/JSC.0b013e3181b073a8}, pmid = {19675466}, issn = {1533-4287}, mesh = {Apnea/*physiopathology ; Athletic Performance/physiology ; Forced Expiratory Volume/physiology ; Humans ; Hypoxia/physiopathology ; Male ; Motor Skills/physiology ; Oxygen Consumption/physiology ; Respiratory Mechanics/physiology ; Swimming/*physiology ; Young Adult ; }, abstract = {Triathletes and elite breath-hold divers show an adaptive response to hypoxia induced by repeated epochs of breath holding. We hypothesized that hypoxic training could also improve swimming coordination. Before and after a 3-month breath-hold training program, 4 male swimmers performed a maximal incremental test on bicycle and a 50-m front crawl race at maximal speed without breathing so that interarm coordination could be assessed. Swim velocity, stroke rate (SR), stroke length (SL), and the arm stroke phases were calculated from video analysis. Arm coordination was quantified in terms of an index of coordination (IdC) based on the time gap between the propulsive phases of each arm. After apnea training, the forced expiratory volume in 1 second was higher (4.85 +/- 0.78 vs. 4.94 +/- 0.81 L, p < 0.05), with concomitant increases in VO2peak, minimal arterial oxygen saturation, and respiratory compensation point values (W and W x kg(-1)) during the incremental test. Swimming performance was not improved (clean velocity and time on 50 m); however, SR was decreased and SL and IdC were increased. These results indicate that apnea training improves effectiveness at both peak exercise and submaximal exercise and can also improve swimming technique by promoting greater propulsive continuity.}, } @article {pmid19669474, year = {2008}, author = {Modolo, J and Henry, J and Beuter, A}, title = {Dynamics of the subthalamo-pallidal complex in Parkinson's disease during deep brain stimulation.}, journal = {Journal of biological physics}, volume = {34}, number = {3-4}, pages = {251-266}, pmid = {19669474}, issn = {0092-0606}, abstract = {The dynamics of the subthalamo-pallidal complex in Parkinson's disease during deep brain stimulation (DBS) were studied using two models, a simple firing-rate model and a population-based model. We extended the simple firing-rate model of the complex formed by the subthalamic nucleus (STN) and the external segment of the Globus Pallidus (GPe) to explore its dynamical regime during DBS. More specifically, the modulation of neuronal activity (i.e., pattern and amplitude) during DBS was studied. A similar approach was used with the population-based model. Simulation results revealed a gradual decrease in bursting activity in STN cells when the DBS frequency increased. In addition, the contribution of the stimulation current type (mono- or biphasic) to the results was also examined. A comparison of the two models indicated that the population-based model was more biologically realistic and more appropriate for exploring DBS mechanisms. Understanding the underlying mechanisms of DBS is a prerequisite for developing new stimulation protocols.}, } @article {pmid19669408, year = {2010}, author = {Kamal, M and Shaaban, AM and Zhang, L and Walker, C and Gray, S and Thakker, N and Toomes, C and Speirs, V and Bell, SM}, title = {Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {121}, number = {3}, pages = {555-563}, doi = {10.1007/s10549-009-0500-4}, pmid = {19669408}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Immunohistochemistry ; Membrane Proteins/*metabolism ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Tumor Suppressor Proteins ; }, abstract = {CUB and SUSHI multiple domain protein 1 (CSMD1) is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade (P = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46-1.43, P = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46-1.5, P = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that CSMD1 is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction.}, } @article {pmid19664142, year = {2009}, author = {Sidhu, M and Griffiths, MM and Bradley, DS}, title = {Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis.}, journal = {Clinical and experimental immunology}, volume = {157}, number = {3}, pages = {350-358}, pmid = {19664142}, issn = {1365-2249}, support = {R01 AR030752/AR/NIAMS NIH HHS/United States ; R56 AR030752/AR/NIAMS NIH HHS/United States ; AR30752/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Collagen/pharmacology ; Cytokines/analysis/blood ; Dendritic Cells/drug effects/immunology/*transplantation ; HLA Antigens/genetics ; HLA-DQ Antigens/genetics ; Humans ; Immunoglobulin G/blood ; Immunohistochemistry ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Polychondritis, Relapsing/genetics/immunology/*therapy ; Treatment Outcome ; Vaccination ; }, abstract = {Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6alphabeta8alphabeta transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6alphabeta8alphabeta transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5.5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3.5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.}, } @article {pmid19663185, year = {2009}, author = {Lisitsyna, TA and Vel'tishchev, DIu and Seravina, OF and Kovalevskaia, OB and Marchenko, AS and Novikova, DS and Novikov, AA and Aleksandrova, EN and Nasonov, EL}, title = {[Prevalence of mental disorders in SLE patients: correlations with the disease activity and comorbid chronic conditions].}, journal = {Terapevticheskii arkhiv}, volume = {81}, number = {6}, pages = {10-16}, pmid = {19663185}, issn = {0040-3660}, mesh = {Adult ; Antiphospholipid Syndrome/complications/drug therapy ; C-Reactive Protein/analysis ; Cytokines/blood ; Female ; Glucocorticoids/administration & dosage/*therapeutic use ; Heart Diseases/complications/diagnosis/drug therapy ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Erythematosus, Systemic/*complications/diagnosis/drug therapy ; Male ; Mental Disorders/diagnosis/*epidemiology ; Middle Aged ; Prevalence ; Russia/epidemiology ; Young Adult ; }, abstract = {AIM: To study effects of the disease activity and comorbid chronic conditions on the incidence of mental disorders in patients with systemic lupus erythematosus (SLE) treated in the State Institute of Rheumatology, RAMS.

MATERIAL AND METHODS: A total of 115 patients with documented SLE (age 24-45 years, median 34 years, SLE duration 4-17, median 8 years) participated in the study. SLE activity was evaluated by SLEDAI scale, atherosclerosis--by ultrasonic arterial dopplerography, mental disorders--by psychological and psychic scales according to IDC-10.

RESULTS: Mental disorders were detected in 76 of 115 (66%) patients: anxiety and depression (83%), depression episodes (40%), maladaptation (24%), generalized anxiety (10%), dysthymia (9%). Manifest cognitive disorders were seen in 7% of examinees. SLE patients with and without mental disorders did not differ by age, gender, SLE duration and activity, cumulative doses of glucocorticoids and cytotoxic drugs, but differed by diagnosed atherosclerosis (23 and 8%, respectively). All SLE patients with the history of myocardial infarction had mental disorders. SLE patients with antiphospholipid syndrome had mental disorders in 85%, while controls--in 49%.

CONCLUSION: Mental disorders are found frequently in SLE patients (66%). 83% of these disorders are anxiodepressive. Incidence of mental disorders in SLE patients do not correlate with age, gender, SLE duration and activity, doses of glucocorticoids and cytotoxic drugs, but correlate with comorbid diseases (atherosclerosis, myocardial infarction, acute cerebral attacks, antiphospholipid syndrome and Sjogren's syndrome.}, } @article {pmid19662489, year = {2011}, author = {Scally, N and Campbell, W and Hall, S and McCusker, G and Stirling, WJ}, title = {Invasive ductal carcinoma arising within a breast hamartoma.}, journal = {Irish journal of medical science}, volume = {180}, number = {3}, pages = {767-768}, pmid = {19662489}, issn = {1863-4362}, mesh = {Aged ; Biopsy, Needle ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Hamartoma/diagnostic imaging/*pathology ; Humans ; Lymph Nodes/pathology ; Mammography ; }, abstract = {INTRODUCTION: Malignant transformation within hamartoma of the breast is uncommon. Invasive ductal or lobular carcinoma of the breast with this aetiology has been noted rarely in the literature.

CONCLUSION: We discuss the diagnosis, radiology and pathology of a 79-year-old lady with an invasive ductal carcinoma arising within a breast hamartoma.}, } @article {pmid19657912, year = {2010}, author = {Raboutet, C and Sauzeon, H and Corsini, MM and Rodrigues, J and Langevin, S and N'kaoua, B}, title = {Performance on a semantic verbal fluency task across time: dissociation between clustering, switching, and categorical exploitation processes.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {32}, number = {3}, pages = {268-280}, doi = {10.1080/13803390902984464}, pmid = {19657912}, issn = {1744-411X}, mesh = {Adult ; Attention/physiology ; Cluster Analysis ; Cognition/*physiology ; Concept Formation/*physiology ; Female ; Humans ; Language Tests ; Male ; Mental Recall/*physiology ; Neuropsychological Tests ; Semantics ; Time Factors ; Verbal Behavior/*physiology ; Vocabulary ; }, abstract = {The aims of this study were to investigate semantic retrieval processes and errors across time during a semantic fluency task and to specify their components (i.e., executive vs. semantic). To do so, we analyzed the productions of 50 healthy participants (using the "supermarket" fluency task). The scores were compared before and after a 30-s interval. Across time, the results showed a decrease in the number of words produced and hard switching. Cluster switching and the number of intrusions remained constant, while clustering, and both the number of exemplars and repetitions increased. These results are discussed in terms of a progressive involvement of a semantic cognitive strategy of retrieval.}, } @article {pmid19657752, year = {2010}, author = {Liu, C and Zhang, H and Shuang, C and Lu, Y and Jin, F and Xu, H and Lu, P}, title = {Alterations of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications.}, journal = {Medical oncology (Northwood, London, England)}, volume = {27}, number = {3}, pages = {747-752}, pmid = {19657752}, issn = {1559-131X}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Transformation, Neoplastic/genetics ; Disease Progression ; *Estrogens ; Female ; *Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Genes, p53 ; Humans ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Neoplasms, Hormone-Dependent/*metabolism/pathology ; *Progesterone ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/*biosynthesis/genetics ; Receptors, Progesterone/*biosynthesis/genetics ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {The aim of the study is to investigate the alterations in expression of estrogen receptor alpha (ER), progesterone receptor (PgR), c-erbB2 gene (HER-2/neu), and P53 protein in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC), and the association between their expression and clinicopathologic findings. The mastectomy specimens of 520 cases containing both DCIS and IDC were examined. The expression of ER, PgR, HER-2/neu, and P53 proteins were examined by immunohistochemistry. Linear regression was used to investigate the correlation among ER, PgR, HER-2/neu, P53 protein expression, and the clinicopathologic factors. There was a significant decrease of ER and PgR expression in IDC compared to DCIS (32.81 vs. 21.05%, chi(2) = 4.45, P = 0.035; 26.56 vs. 15.57%, chi(2) = 4.82, P = 0.028, respectively). In contrast, there was a significant increase of HER-2/neu expression in IDC compared to DCIS (10.94 vs. 21.27%, chi(2) = 3.88, P = 0.049). However, there was no significant difference in expression of p53 between DCIS and IDC. In both DCIS and IDC, a significant positive correlation was observed between ER and PgR receptor expression (r = 0.67, P = 0.00; r = 0.56, P = 0.00, respectively). In conclusion, these findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER, PgR, and HER-2/neu. The underlying mechanisms of these alterations need further investigation.}, } @article {pmid19657714, year = {2012}, author = {Kai, M and Tada, K and Tamura, M and Gomi, N and Horii, R and Akiyama, F and Iwase, T}, title = {Breast cancer associated with mammary hamartoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {19}, number = {2}, pages = {183-186}, doi = {10.1007/s12282-009-0147-3}, pmid = {19657714}, issn = {1880-4233}, mesh = {Aged ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Diagnosis, Differential ; Female ; Fibroadenoma/*diagnosis ; Hamartoma/*diagnosis ; Humans ; Lipoma/*diagnosis ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {Mammary hamartoma is an infrequent, nonmalignant lesion. Only 12 cases of carcinomas associated with a hamartoma have been previously documented in the literature. We describe a case of invasive ductal carcinoma arising in the mammary hamartoma during the follow-up period of a previously diagnosed hamartoma.}, } @article {pmid19657711, year = {2009}, author = {Sasaki, Y and Tsuda, H}, title = {Clinicopathological characteristics of triple-negative breast cancers.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {4}, pages = {254-259}, doi = {10.1007/s12282-009-0153-5}, pmid = {19657711}, issn = {1880-4233}, mesh = {Breast Neoplasms/chemistry/*pathology ; Female ; Humans ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; }, abstract = {Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors and HER2. Although patients with TNBC tend to have a poor prognosis, only chemotherapy is expected to be effective because no therapeutic targets have yet been established. DNA microarray analyses have proved that TNBCs are composed of the basal-like subtype and normal breast (or unclassified) subtype, the former being correlated with an aggressive clinical course. Histological types of TNBCs are reported to be common with those of basal-like subtype, comprising high-grade invasive ductal carcinoma, no special type [solid-tubular carcinoma (or atypical medullary carcinoma), invasive ductal carcinoma with a large central acellular zone], typical medullary carcinoma, and metaplastic carcinomas. The basal-like subtype is characterized by the expression of myoepithelial/basal markers and molecular changes including TP53 gene mutations, BRCA1 inactivation, and many chromosomal alterations. New target molecules for the treatment of TNBCs are under extensive investigation, and their clinical application is awaited.}, } @article {pmid19653048, year = {2009}, author = {Ikenaga, N and Ohuchida, K and Mizumoto, K and Yu, J and Fujita, H and Nakata, K and Ueda, J and Sato, N and Nagai, E and Tanaka, M}, title = {S100A4 mRNA is a diagnostic and prognostic marker in pancreatic carcinoma.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {13}, number = {10}, pages = {1852-1858}, pmid = {19653048}, issn = {1873-4626}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Carcinoma, Pancreatic Ductal/*diagnosis/*genetics ; Female ; Gene Expression ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*diagnosis/*genetics ; Prognosis ; RNA, Messenger ; S100 Calcium-Binding Protein A4 ; S100 Proteins/*genetics ; Survival Analysis ; }, abstract = {OBJECTIVE: The aim of this study is to evaluate the clinical significance of S100A4 mRNA expression in pancreatic cancer.

MATERIALS AND METHODS: We obtained invasive ductal carcinoma (IDC) cells from ten lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 20 lesions, and normal ductal cells from 20 normal pancreatic tissues by laser microdissection of frozen tissues. S100A4 expression was examined in the microdissected cells and in formalin-fixed paraffin-embedded (FFPE) samples of 87 pancreatic cancers by quantitative reverse transcription-polymerase chain reaction.

RESULTS: IDC cells expressed higher levels of S100A4 than IPMN cells (P = 0.002) and normal ductal cells (P < 0.001), although the difference between IPMN cells and normal ductal cells was not statistically significant (P = 0.070). Analysis of FFPE samples revealed that high S100A4 expression was significantly associated with a shorter overall survival (P = 0.023). In immunohistochemical analysis, the extent of S100A4 mRNA expression was significantly correlated with the expression of S100A4 protein (P = 0.028).

CONCLUSION: S100A4 could be a marker for malignancy in pancreatic tumors and for poor prognosis in patients with pancreatic cancer.}, } @article {pmid19652229, year = {2009}, author = {Wong, CS and Chu, YC and Wong, KW and Yeung, TH and Ma, KF}, title = {Is ultrasonography-guided modified coaxial core biopsy of the breast a better technique?.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {15}, number = {4}, pages = {246-248}, pmid = {19652229}, issn = {1024-2708}, mesh = {Adult ; Aged ; Biopsy, Needle/*methods ; Breast/*pathology ; Breast Neoplasms/diagnostic imaging/*pathology ; Female ; Hong Kong ; Humans ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Ultrasonography, Interventional ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: To compare the diagnostic rate, patient comfort, and complications of ultrasonography-guided breast biopsy using a modified coaxial technique with ultrasonography-guided fine needle aspiration and traditional core biopsy. A secondary objective was to describe the use of the coaxial technique for the biopsy of breast lesions and our initial experience.

DESIGN: Retrospective study.

SETTING: A regional hospital in Hong Kong.

PATIENTS: Patients, who were referred for ultrasonography-guided fine needle aspiration or biopsy from 23 November 2007 to 19 March 2008, were divided into three groups. For breast lesions of 8 mm or smaller, fine needle aspirations were performed. For breast lesions larger than 8 mm, the patients were randomly divided into groups receiving traditional core biopsies and coaxial biopsies. The pathological reports were reviewed.

MAIN OUTCOME MEASURES: Diagnostic rate, patient comfort assessed in terms of pain, and any procedural complications.

RESULTS: A total of 45 ultrasonography-guided fine needle aspirations or biopsies of breast lesions were performed. All core biopsies using the traditional core technique (n=15) and coaxial technique (n=16) were diagnostic. While for fine needle aspirations, three (21%) of 14 were not diagnostic and repeat biopsies were undertaken for the corresponding patients. Except for one breast lesion biopsied with the coaxial technique that revealed invasive ductal carcinoma, all others yielded benign lesions. The average pain score for coaxial biopsies was 2.2, while for traditional core biopsies and fine needle aspirations, average scores were 3.7 and 3.8, respectively (P=0.022). No procedure-related complication was documented with either of the three techniques.

CONCLUSION: Modified coaxial core biopsy of the breast has an optimal diagnostic rate and hence avoids the need for repeat biopsies. It is associated with better patient comfort and no increase in the risk of complications.}, } @article {pmid19648285, year = {2009}, author = {Poole, JA and Thiele, GM and Alexis, NE and Burrell, AM and Parks, C and Romberger, DJ}, title = {Organic dust exposure alters monocyte-derived dendritic cell differentiation and maturation.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {297}, number = {4}, pages = {L767-76}, pmid = {19648285}, issn = {1522-1504}, support = {K08 ES015522-02/ES/NIEHS NIH HHS/United States ; K08: ES015522-01/ES/NIEHS NIH HHS/United States ; K08 ES015522-03/ES/NIEHS NIH HHS/United States ; 1R01OH008539-01/OH/NIOSH CDC HHS/United States ; K08 ES015522/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*immunology ; Cells, Cultured ; Cytokines/immunology/*metabolism ; Dendritic Cells/*immunology/metabolism ; Dust/*immunology ; Flow Cytometry ; Housing, Animal ; Humans ; Lymphocytes/*immunology/metabolism ; Monocytes/*immunology/metabolism ; Phagocytosis ; Swine ; }, abstract = {Organic dust exposure in agricultural animal environments results in airway diseases. Dendritic cells (DCs) orchestrate inflammatory immune response in the airways, but little is known about how organic dust affects differentiation and maturation of monocyte-derived immature and mature DCs (iDCs, mDCs). Peripheral blood monocytes were differentiated in vitro into iDCs with granulocyte-macrophage colony stimulating factor + IL-4 (6 days) with and without swine facility organic dust extract (ODE, 0.1%). Unlike control iDCs, ODE-conditioned iDCs maintained key monocyte properties (increased mCD14, increased phagocytic ability) while expressing DC features [increased mCD83, HLA-DR, CD80, CD86, diminished cytokine (TNF-alpha, IL-6) responsiveness]. At day 6, iDCs were cultured for an additional 48 h (days 7 and 8) with lipopolysaccharide (LPS) to induce mDCs. ODE-conditioned mDCs maintained high expression of mCD14(+) and elevated phagocytosis while their DC features weakened as evidenced by decreased CD11c, CD83, HLA-DR, CD86, and CCR7 expression and reduced lymphocyte-stimulating capacity. Similar results were observed when monocytes were exposed to ODE for only the first 48 h and with ODE depleted of endotoxin. Control iDCs exposed to ODE during the final 2 days of iDC maturation (days 7 and 8) did not differ from control (no ODE) iDCs in surface marker expression and phagocytic ability, but exhibited enhanced lymphocyte-stimulating capacity. Dust exposure alters monocyte differentiation to iDCs and prevents maturation of iDC to mDCs. The first 48 h of monocyte differentiation appears to be the susceptible period to exposure. Environmental exposures present during early monocyte differentiation may impact the critical balance of DCs in the lung.}, } @article {pmid19645793, year = {2009}, author = {Ayatollahi, H and Ghaffarzadegan, K and Sharifi, N and Farahmand, MJ and Jarafian, AH}, title = {Comparison of two score systems in Bcl-2 and Bax protein expression in invasive ductal carcinoma of breast and relation with oestrogen and progestrone receptors.}, journal = {The breast journal}, volume = {15}, number = {3}, pages = {310-312}, doi = {10.1111/j.1524-4741.2009.00727.x}, pmid = {19645793}, issn = {1524-4741}, mesh = {Apoptosis ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; bcl-2-Associated X Protein/*metabolism ; }, } @article {pmid19645781, year = {2009}, author = {El-Gohary, YM and Metwally, G and Saad, RS and Robinson, MJ and Mesko, T and Poppiti, RJ}, title = {Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast.}, journal = {The breast journal}, volume = {15}, number = {3}, pages = {261-267}, doi = {10.1111/j.1524-4741.2009.00715.x}, pmid = {19645781}, issn = {1524-4741}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/*analysis ; Antibodies, Monoclonal, Murine-Derived ; Biomarkers, Tumor/*analysis ; Breast/blood supply ; Breast Neoplasms/*blood supply/pathology ; Carcinoma, Intraductal, Noninfiltrating/*blood supply/pathology ; Case-Control Studies ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Vessels/chemistry/*pathology ; Microcirculation ; Middle Aged ; Neoplasm Invasiveness ; Platelet Endothelial Cell Adhesion Molecule-1/*analysis ; Prognosis ; }, abstract = {We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression."}, } @article {pmid19639594, year = {2009}, author = {Ferreira, GB and van Etten, E and Lage, K and Hansen, DA and Moreau, Y and Workman, CT and Waer, M and Verstuyf, A and Waelkens, E and Overbergh, L and Mathieu, C}, title = {Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D.}, journal = {Proteomics}, volume = {9}, number = {14}, pages = {3752-3764}, doi = {10.1002/pmic.200800848}, pmid = {19639594}, issn = {1615-9861}, mesh = {Blotting, Western ; Cell Differentiation/drug effects ; Cells, Cultured ; Cytoskeleton/metabolism ; Dendritic Cells/cytology/*drug effects/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Proteome/*analysis ; Vitamin D/*analogs & derivatives/*pharmacology ; Vitamins/*pharmacology ; }, abstract = {Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation of a tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence or absence of TX527 (10(-8) M) (n=4). Protein samples were separated into two different pH ranges (pH4-7 and 6-9), analyzed by 2-D DIGE and differentially expressed spots (p<0.01) were identified by MALDI-TOF/TOF (76.3 and 70.7% in iDC and mature DCs, respectively). Differential protein expression revealed three protein groups predominantly affected by TX527 treatment, namely proteins involved in cytoskeleton structure, in protein biosynthesis/proteolysis and in metabolism. Moreover, protein interactome-network analysis demonstrated close interaction between these different groups (p<0.001) and morphological and functional analyses confirmed the integrated effect of TX527 on human DCs, resulting in a cell with altered morphology, cell surface marker expression, endocytic and migratory capacity.}, } @article {pmid19639398, year = {2009}, author = {Di Biase, L and Burkhardt, JD and Lakkireddy, D and Pillarisetti, J and Baryun, EN and Biria, M and Horton, R and Sanchez, J and Gallinghouse, GJ and Bailey, S and Beheiry, S and Hongo, R and Hao, S and Tomassoni, G and Natale, A}, title = {Mapping and ablation of ventricular arrhythmias with magnetic navigation: comparison between 4- and 8-mm catheter tips.}, journal = {Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing}, volume = {26}, number = {2}, pages = {133-137}, pmid = {19639398}, issn = {1572-8595}, mesh = {Body Surface Potential Mapping/*instrumentation ; Catheter Ablation/*instrumentation ; Equipment Design ; Equipment Failure Analysis ; Female ; Humans ; Magnetics/*instrumentation ; Male ; Middle Aged ; Surgery, Computer-Assisted/*instrumentation/methods ; Tachycardia, Ventricular/*diagnosis/*surgery ; *Transducers ; Treatment Outcome ; }, abstract = {INTRODUCTION: Remote magnetic navigation (RMN) has been reported as an effective and safe tool to overcome the need for advanced operator skill in the treatment of complex arrhythmias. We report a series of patients undergoing radiofrequency catheter ablation of ventricular arrhythmias (VAs) using RMN with either a 4-mm catheter tip or an 8-mm catheter tip at four different centers.

METHODS: Sixty-five patients with clinical and symptomatic history of Vas were included. Two different magnetic catheters were used to deliver radiofrequency applications remotely. When ablation with the RMN catheters failed, a manual irrigated catheter was used to eliminate the VAs. Post-ablation pacing maneuvers were utilized to verify the inducibility of Vas.

RESULTS: Twenty-eight patients (43%) had ischemic cardiomyopathy [coronary artery disease (CAD)], 16 patients (25%) had non-ischemic cardiomyopathy [idiopathic dilated cardiomyopathy (IDC)], and 21 patients (32%) had structurally normal hearts (SNH) or right ventricle outflow tract tachycardia (RVOT). In patients with structural heart disease (CAD, IDC), success was achieved in 22% with the 4-mm catheter tip and in 59% with the 8-mm catheter tip (p = 0.014). In patients with SNH/RVOT, success was achieved in 85% with the 4-mm catheter tip and in 87% with the 8-mm catheter tip (p = 1.00).

CONCLUSIONS: Our findings showed that, with RMN, there is an increased success related to the catheter tip utilized. However, in patients with right ventricular outflow origin, the standard 4-mm tip provided adequate lesions for successful ablation in most patients.}, } @article {pmid19637504, year = {2009}, author = {Eliahou, R and Sella, T and Allweis, T and Samet, Y and Libson, E and Sklair-Levy, M}, title = {Magnetic resonance-guided interventional procedures of the breast: initial experience.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {11}, number = {5}, pages = {275-279}, pmid = {19637504}, issn = {1565-1088}, mesh = {Adult ; Aged ; Biopsy, Needle/methods ; Breast/*pathology ; Breast Diseases/diagnosis/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Female ; Gadolinium ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Radiography ; Retrospective Studies ; Ultrasonography ; }, abstract = {BACKGROUND: Magnetic resonance imaging of the breast has emerged as a valuable imaging tool in addition to conventional imaging modalities. It has high sensitivity for malignant lesions and can detect mammographically, sonographically and clinically occult cancers. "MR only" lesions are best biopsied under MR guidance; however, this may be a challenging task.

OBJECTIVES: To evaluate our initial clinical experience with MR-guided core needle breast biopsy and MR-guided needle localization.

METHODS: We retrospectively evaluated 81 women with 97 lesions, who were scheduled for guided core needle biopsy or MR-guided needle localization followed by surgery. Lesions were categorized as malignant, high risk, or benign according to the BI-RADS MR classification system. MR findings were compared with final histopathology or with follow-up imaging findings.

RESULTS: Fifteen (16%) lesions were malignant (9 invasive ductal carcinoma, 2 invasive lobular carcinoma, 4 ductal carcinoma in situ); 7 (7%) lesions were high risk (4 atypical ductal hyperplasia, 3 radial scars); 75 (77%) lesions were benign, mainly fibrocystic changes. Other benign findings were sclerosing adenosis, pseudoangiomatous stromal hyperplasia, fat necrosis, intraductal papilloma, fibroadenoma, capillary hemangioma, and florid ductal hyperplasia. No major complications were encountered.

CONCLUSIONS: MR-guided interventional procedures of the breast are accurate, safe and feasible methods for sampling breast lesions detected only by MR and have become a significant tool in the management of certain patients.}, } @article {pmid19636625, year = {2010}, author = {Rizzo, M and Iyengar, R and Gabram, SG and Park, J and Birdsong, G and Chandler, KL and Mosunjac, MB}, title = {The effects of additional tumor cavity sampling at the time of breast-conserving surgery on final margin status, volume of resection, and pathologist workload.}, journal = {Annals of surgical oncology}, volume = {17}, number = {1}, pages = {228-234}, doi = {10.1245/s10434-009-0643-x}, pmid = {19636625}, issn = {1534-4681}, mesh = {Breast Neoplasms/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Staging ; Prognosis ; *Reoperation ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {INTRODUCTION: Margin status is an important prognostic factor for local recurrence after breast-conserving surgery (BCS) in patients with breast malignancy. It is unclear whether the removal of additional tumor cavity margins reduces the reoperation rate and is cosmetically acceptable. This study compares the reoperation rates, volume of breast excised in cm(3), and number of pathology slides examined in two groups of patients who underwent BCS with or without four or five additional margins (BCS + M).

METHODS: We retrospectively analyzed 320 patients who underwent BCS or BCS + M for stage 0-I-II breast cancer from 2004 to 2007. We classified the margins as negative (>or=1 mm), close (<1 mm), or positive based on the distance from the tumor to the margin of resection.

RESULTS: Of 320 cases analyzed, 199 (62.2%) underwent BCS and 121 (37.8%) had BCS + M. Overall, patients with BCS + M had a higher negative margins rate (85.1% vs. 57.2%, P < 0.05) and a lower reoperation rate. However, when ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were analyzed separately, only patients with IDC showed a higher negative margin rate (91% vs. 62.1%, P < 0.001) and a lower volume of breast tissue excised (205.63 vs. 392.27, P = 0.03). There was no significant increase in pathology workload in both groups.

CONCLUSIONS: Resection of four to five additional margins during BCS for early-stage invasive breast cancer results in a higher rate of negative microscopic margins, lower volume of breast excised, and subsequently, a lower reoperation rate. The advantages of this approach include improved patient satisfaction and decreased cost.}, } @article {pmid19635920, year = {2009}, author = {Tanaka, M and Krutzik, SR and Sieling, PA and Lee, DJ and Rea, TH and Modlin, RL}, title = {Activation of Fc gamma RI on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {183}, number = {4}, pages = {2349-2355}, pmid = {19635920}, issn = {1550-6606}, support = {A122553//PHS HHS/United States ; R37 AI047868/AI/NIAID NIH HHS/United States ; R37 AI047868-09/AI/NIAID NIH HHS/United States ; AR40312/AR/NIAMS NIH HHS/United States ; R01 AI022553-24/AI/NIAID NIH HHS/United States ; R01 AR040312/AR/NIAMS NIH HHS/United States ; R01 AI022553/AI/NIAID NIH HHS/United States ; R01 AR040312-19/AR/NIAMS NIH HHS/United States ; }, mesh = {Antigens, CD1/biosynthesis/genetics ; Autoimmune Diseases/blood/*immunology/pathology ; Cell Adhesion Molecules/metabolism ; Cell Differentiation/genetics/*immunology ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism/pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/physiology ; Humans ; Immune Complex Diseases/blood/immunology/pathology ; Inflammation Mediators/blood/physiology ; Lectins, C-Type/metabolism ; Lymphocyte Activation/genetics/immunology ; Monocytes/cytology/*immunology/metabolism ; Receptors, Cell Surface/metabolism ; Receptors, IgG/biosynthesis/*blood/genetics ; T-Lymphocyte Subsets/*immunology/metabolism/pathology ; }, abstract = {The formation of immune complexes results in activation of the innate immune system and subsequent induction of host inflammatory responses. In particular, the binding of IgG immune complexes to FcgammaR on monocytes triggers potent inflammatory responses leading to tissue injury in disease. We investigated whether activation of monocytes via FcgammaR induced cell differentiation, imparting specific inflammatory functions of the innate immune response. Human IgG alone induced monocytes to differentiate into cells with an immature dendritic cell (iDC) phenotype, including up-regulation of CD1b, CD80, CD86, and CD206. Differentiation into CD1b(+) iDC was dependent on activation via CD64 (FcgammaRI) and induction of GM-CSF. The human IgG-differentiated iDC were phenotypically different from GM-CSF-derived iDC at the same level of CD1b expression, with higher cell surface CD86, but lower MHC class II, CD32, CD206, and CD14. Finally, in comparison to GM-CSF-derived iDC, IgG-differentiated iDC were more efficient in activating T cells in both autologous and allogeneic mixed lymphocyte reactions but less efficient at presenting microbial Ag to T cells. Therefore, activation of FcgammaRI on monocytes triggers differentiation into specialized iDC with the capacity to expand autoreactive T cells that may contribute to the pathogenesis of immune complex-mediated tissue injury.}, } @article {pmid19633015, year = {2009}, author = {Hombach, V and Merkle, N and Torzewski, J and Kraus, JM and Kunze, M and Zimmermann, O and Kestler, HA and Wöhrle, J}, title = {Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy.}, journal = {European heart journal}, volume = {30}, number = {16}, pages = {2011-2018}, pmid = {19633015}, issn = {1522-9645}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*mortality/physiopathology ; *Electrocardiography ; Female ; Humans ; Kaplan-Meier Estimate ; *Magnetic Resonance Angiography ; Male ; Middle Aged ; Prognosis ; Risk Factors ; }, abstract = {AIMS: Clinical parameters are weak predictors of outcome in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prognostic value of cardiac magnetic resonance (CMR) parameters in addition to conventional clinical and electrocardiographic characteristics.

METHODS AND RESULTS: One hundred and forty-one IDC patients were studied. QRS and QTc intervals were measured in 12-lead surface electrocardiogram. Patients were followed for median 1339 days, including 483 patient-years. The primary endpoint-cardiac death or sudden death-occurred in 25 (18%) patients, including 16 patients with cardiac death, 3 patients with sudden cardiac death (SCD), and 6 patients with ICD shock. Late gadolinium enhancement (LGE) was detected in 36 patients (26%). Kaplan-Meier survival analysis displayed QRS >110 ms (P = 0.010), the presence of LGE (P = 0.037), and diabetes mellitus (P < 0.001) as significant parameters for a worse outcome. Multivariable analysis revealed cardiac index (P < 0.001), right ventricular end-diastolic volume index (RVEDVI) (P = 0.006) derived from CMR imaging, the presence of diabetes mellitus (P = 0.006), and QRS >110 ms (P = 0.045) as significant predictors for the primary endpoint.

CONCLUSION: Cardiac index and RVEDVI derived from CMR imaging in addition to QRS duration >110 ms from conventional surface ECG and diabetes mellitus provide prognostic impact for cardiac death and SCD in patients with IDC.}, } @article {pmid19632522, year = {2009}, author = {Ogimoto, A and Okayama, H and Nagai, T and Ohtsuka, T and Suzuki, J and Inoue, K and Nishimura, K and Shigematsu, Y and Tabara, Y and Kohara, K and Miki, T and Higaki, J}, title = {Association of monocyte chemoattractant protein 1 gene polymorphism with susceptibility to nonfamilial idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiology}, volume = {54}, number = {1}, pages = {66-70}, doi = {10.1016/j.jjcc.2009.04.001}, pmid = {19632522}, issn = {1876-4738}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathy, Dilated/*genetics ; Chemokine CCL2/*genetics ; Child ; Female ; Genetic Markers ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Young Adult ; }, abstract = {BACKGROUND: The cytotoxic action of leukocytes is known to be a probable cause of the cardiac myocyte damage seen in idiopathic dilated cardiomyopathy (IDC). Monocyte chemoattractant protein 1 (MCP-1) contributes to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. MCP-1 has been reported to be dynamically regulated in IDC and may contribute to the deterioration of left ventricular function. In addition, a polymorphism at -2518 (G/A) in the MCP-1 gene affects the level of MCP-1 expression in response to an inflammatory stimulus.

METHODS AND RESULTS: We genotyped the polymorphism at -2518 G/A in the MCP-1 gene in 73 Japanese patients with nonfamilial IDC and 349 healthy controls. The distribution of the MCP-1 genotypes in the IDC patients differed significantly from the controls (p=0.016). In a dominant G allele model, there was a significant difference in the distribution of genotypes between the two groups (p<0.01). The odds ratio for nonfamilial IDC associated with the GG vs. non-GG genotype was 10.4 (95% CI=1.7-64.5) after adjustment for the confounding factors.

CONCLUSIONS: These findings suggest that the G allele at -2518 in the MCP-1 gene may be a novel genetic marker of susceptibility to nonfamilial IDC.}, } @article {pmid19629002, year = {2009}, author = {Kato, K and Yamada, S and Sugimoto, H and Kanazumi, N and Nomoto, S and Takeda, S and Kodera, Y and Morita, S and Nakao, A}, title = {Prognostic factors for survival after extended pancreatectomy for pancreatic head cancer: influence of resection margin status on survival.}, journal = {Pancreas}, volume = {38}, number = {6}, pages = {605-612}, doi = {10.1097/MPA.0b013e3181a4891d}, pmid = {19629002}, issn = {1536-4828}, mesh = {Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/pathology/*surgery/therapy ; Pancreaticoduodenectomy/*methods ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVES: Although a positive resection margin has been reported to be a strong prognostic factor after resection for pancreatic cancer, several studies indicated that resection status did not independently affect survival. The aim of this study was to examine the influence of resection margin status on survival after extended radical resection for pancreatic head cancer.

METHODS: One hundred thirty-eight cases of pancreatoduodenectomy and 38 cases of pylorus-preserving pancreatoduodenectomy for invasive ductal carcinoma of the pancreas were retrospectively analyzed.

RESULTS: The resection margins were negative (R0) in 115 patients (65.3%), microscopically positive (R1) in 38 patients (21.6%), and grossly positive (R2) in 23 patients (13.1%). Patients with R1 resection survived significantly shorter (median survival time [MST], 9.4 months) than R0 resection patients (MST, 15.2 months) but survived longer than R2 resection patients (MST, 6.2 months). By multivariate analysis, R2 resection, together with lymph node metastasis, portal venous system, and extrapancreatic nerve plexus invasions, independently affected the overall survival, but R1 resection was not significantly influential.

CONCLUSIONS: R2 resection was an independent predictor of poor prognosis after pancreatoduodenectomy/pylorus-preserving pancreatoduodenectomy, whereas R1 resection did not independently affect the survival.}, } @article {pmid19628225, year = {2010}, author = {Pappo, I and Spector, R and Schindel, A and Morgenstern, S and Sandbank, J and Leider, LT and Schneebaum, S and Lelcuk, S and Karni, T}, title = {Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.}, journal = {The Journal of surgical research}, volume = {160}, number = {2}, pages = {277-281}, doi = {10.1016/j.jss.2009.02.025}, pmid = {19628225}, issn = {1095-8673}, mesh = {Adult ; Biopsy ; Breast/pathology/surgery ; Breast Neoplasms/*pathology/*surgery ; Female ; Humans ; Intraoperative Care/instrumentation/standards ; *Mastectomy, Segmental ; Pathology, Clinical/*instrumentation/standards ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Spectroscopy, Near-Infrared/*instrumentation/standards ; }, abstract = {BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device.

METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups.

RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC.

CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.}, } @article {pmid19624269, year = {2009}, author = {Hu, X and Zhang, Y and Zhang, A and Li, Y and Zhu, Z and Shao, Z and Zeng, R and Xu, LX}, title = {Comparative serum proteome analysis of human lymph node negative/positive invasive ductal carcinoma of the breast and benign breast disease controls via label-free semiquantitative shotgun technology.}, journal = {Omics : a journal of integrative biology}, volume = {13}, number = {4}, pages = {291-300}, doi = {10.1089/omi.2009.0016}, pmid = {19624269}, issn = {1557-8100}, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast Diseases/*pathology ; Breast Neoplasms/*metabolism/pathology ; Case-Control Studies ; Chromatography, Liquid/methods ; Cluster Analysis ; Computational Biology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Proteome/*analysis ; Proteomics/*methods ; Tandem Mass Spectrometry/methods ; }, abstract = {Serum proteomics provides a useful tool to identify potential biomarkers associated with cancer progression. In the present study, a two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) on a linear ion trap was utilized to identify and compare serum proteins from breast cancer patients. Three groups of 21 human sera, 7 from patients with lymph node-negative invasive ductal carcinoma (IDCB), 7 from patients with lymph node-positive IDCB, and 7 controls from patients with benign breast diseases, were analyzed. Through proteomic analysis, a total of 2,078 proteins were identified with at least two unique peptide hits. By quantification with label-free spectral counting, a fruitful list of serum proteins with significant differences in abundance accompanying the progression of breast cancer was found. Through hierarchical cluster analysis based on the differently expressed proteins in selection, we found that different groups of sera could be distinguished. Among the selected proteins, tenascin-XB (TNXB) was further validated by the ELISA method in 131 serum samples as a promising biomarker for early metastasis of breast cancer. These experiments revealed the valuable potential of label-free quantitative 2D-LC-MS/MS for identification of novel biomarkers for disease progression.}, } @article {pmid19622106, year = {2009}, author = {Turpeinen, AK and Vanninen, E and Magga, J and Tuomainen, P and Kuusisto, J and Sipola, P and Punnonen, K and Vuolteenaho, O and Peuhkurinen, K}, title = {Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy.}, journal = {Clinical physiology and functional imaging}, volume = {29}, number = {6}, pages = {414-419}, doi = {10.1111/j.1475-097X.2009.00887.x}, pmid = {19622106}, issn = {1475-097X}, mesh = {Cardiomyopathy, Dilated/complications/*physiopathology ; Female ; Humans ; Interleukin-6/*blood ; Male ; Middle Aged ; Myocarditis/complications/*physiopathology ; Natriuretic Peptide, Brain/*blood ; Neurotransmitter Agents/*blood ; Peptide Fragments/*blood ; Sympathetic Nervous System/*physiopathology ; Ventricular Dysfunction, Left/etiology/*physiopathology ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood.

METHODS AND RESULTS: We studied 99 patients with IDC (age 54 +/- 1 years, left ventricular ejection fraction (EF) 40 +/- 1%, maximum oxygen uptake (VO(2)max) 20 +/- 1 ml kg(-1) min(-2), mean +/- SEM) by using (123)I-metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)-ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)-6 and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL-6 (r = 0.42, P<0.001 and r = -0.31, P<0.01) and NT-proBNP (r = 0.48, P<0.001 and r = -0.40, P<0.001). During a median follow-up of 4.1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter-defibrillator). In these patients, MIBG washout was higher (53 +/- 4 versus 40 +/- 2%, P = 0.01) and H/M ratio lower (1.38 +/- 0.04 versus 1.51 +/- 0.02, P = 0.01) than in patients without an event.

CONCLUSIONS: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.}, } @article {pmid19616675, year = {2009}, author = {Gimeno, JR and Lacunza, J and García-Alberola, A and Cerdán, MC and Oliva, MJ and García-Molina, E and López-Ruiz, M and Castro, F and González-Carrillo, J and de la Morena, G and Valdés, M}, title = {Penetrance and risk profile in inherited cardiac diseases studied in a dedicated screening clinic.}, journal = {The American journal of cardiology}, volume = {104}, number = {3}, pages = {406-410}, doi = {10.1016/j.amjcard.2009.03.055}, pmid = {19616675}, issn = {1879-1913}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cardiomyopathies/diagnosis/epidemiology/*genetics ; Child ; Consanguinity ; Echocardiography ; Electrocardiography ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Mass Screening ; Middle Aged ; *Penetrance ; Risk Assessment ; Risk Factors ; }, abstract = {Genetically transmitted cardiomyopathies can affect several members in a family. Identification of high-risk patients could lead to a preventive treatment. We report the results of a 5-year experience of a dedicated clinic. Family screening was offered to 493 consecutive unrelated patients; 2,328 subjects (40 +/- 19 years old, 52% men) were evaluated (mean 4.4 relatives/family). Electrocardiography and echocardiography were performed in all cases; additional tests were indicated depending on the disease. Familial study was recommended because of a proband with hypertrophic cardiomyopathy (HC) in 57%, idiopathic dilated cardiomyopathy (IDC) in 14%, arrhythmogenic right ventricular cardiomyopathy (ARVC) in 2%, left ventricular noncompaction in 2%, Brugada syndrome (BS) in 15%, long QT syndrome (LQTS) in 3%, and other conditions in 6%. Familial disease was confirmed in 164 (39%); 43% with HC, 47% with IDC, 25% with ARVC, 33% with left ventricular noncompaction, 28% with BS, and 30% with LQTS. Two hundred twenty-two (44 +/- 20 years old, 60% men) affected relatives were identified (129 of whom were newly diagnosed). Sixty-four patients were newly diagnosed with HC, 40 with IDC, 2 with ARVC, 5 with left ventricular noncompaction, 14 with BS, and 2 with LQTS, in whom appropriate risk stratification and medication, if needed, were initiated (specific medication in 40, 31.0%). Cardioverter-defibrillator implantation was indicated in 4 relatives for primary prevention. Ninety-two (18.7%) had a family history of sudden death (FHSCD). Consanguinity was rare but significantly associated to a higher percentage of family disease (75.0% vs 38.3%, p = 0.003) and family history of sudden death (42.1% vs 17.8, p <0.001). In conclusion, the prevalence of familial disease in inherited cardiac conditions is high. Systematic familial study identified many asymptomatic affected patients who could benefit from early treatment to prevent complications. Dedicated clinics and multidisciplinary teams are needed for proper screening programs.}, } @article {pmid19606200, year = {2009}, author = {Oguntola, AS and Aderonmu, AO and Adeoti, ML and Olatoke, SA and Akanbi, O and Agodirin, SO}, title = {Male breast cancer in LAUTECH Teaching Hospital Osogbo, South Western Nigeria.}, journal = {The Nigerian postgraduate medical journal}, volume = {16}, number = {2}, pages = {166-170}, pmid = {19606200}, issn = {1117-1936}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*pathology/therapy ; Comorbidity ; Hospitals, Teaching ; Humans ; Male ; Mastectomy ; Middle Aged ; Nigeria/epidemiology ; Prevalence ; Retrospective Studies ; Survival Analysis ; Tamoxifen/therapeutic use ; Time Factors ; Treatment Outcome ; }, abstract = {AIM: To assess the prevalence, presentation, treatment and outcome of management of male breast cancer (MBC) in Osogbo, Nigeria.

METHODS: A review of all cases of MBC seen at LAUTECH Teaching Hospital Osogbo between January 2004 and December 2006 was done. The age, presenting symptoms and signs, stage, histology, associated co-morbid illnesses, treatment and outcome of care were all retrieved and analysed.

RESULTS: Seven (8.86%) out of seventy nine cases of breast cancers seen are males. Ages ranged between 38 and 80 years (mean 60.5 median 65 years). They all presented with advanced lesions after a 6 -36 months delay (mean-11.57 months). All were invasive ductal carcinoma. All the four with significant co-morbid illnesses died of them within one week to seven months. Only one patient had mastectomy.

CONCLUSION: MBC constitutes 8.86% of all breast cancer, all presented late with advanced lesions and co-morbid illnesses contributed significantly to mortality.}, } @article {pmid19606195, year = {2009}, author = {Mukhtar-Yola, M and Gwarzo, GD and Galadanci, HS and Tukur, J and Farouk, ZL and Adeleke, SI}, title = {HIV exposed infants: a preliminary report of the Aminu Kano Teaching Hospital experience.}, journal = {The Nigerian postgraduate medical journal}, volume = {16}, number = {2}, pages = {143-148}, pmid = {19606195}, issn = {1117-1936}, mesh = {Bottle Feeding ; Breast Feeding ; *Counseling ; Female ; HIV Infections/epidemiology/*prevention & control/*transmission ; HIV Seropositivity/epidemiology/transmission ; HIV-1 ; Hospitals, Teaching ; Humans ; Infant ; Infant Formula ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention & control ; Male ; Mothers ; Nigeria/epidemiology ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology/*prevention & control ; Socioeconomic Factors ; }, abstract = {UNLABELLED: To determine the Sociodemographic characteristics, infant feeding choices and outcome of HIV exposed neonates attending the paediatric infectious disease clinic (IDC) of Aminu Kano Teaching Hospital Kano.

PATIENTS AND METHODS: The records of all HIV exposed babies were reviewed. One hundred and ninety HIV exposed babies were seen between October 2003-December 2005. Of these 121 were part of the PMTCT programme while 69 were not. A total of 179(94.2%) babies were delivered at term while 11(5.8%) were delivered prematurely, with M: F ratio of 1.2:1.

RESULTS: A substantial number of mothers in the non PMTCT group were diagnosed antenataly or even prior to conception yet they did not avail themselves of the interventions in the PMTCT programme. Reasons given were ignorance, inaccessibility to PMTCT centres and fear of stigmatisation. Breast milk substitute, was the leading choice of mothers in the PMTCT group while breast milk and mixed feeding was practised more in the non-PMTCT group.

CONCLUSION: PMTCT remains the best way of preventing paediatric HIV infection and infant feeding counselling should be family oriented. Provision of free infant formula, PCR machines to enable early diagnosis, waiving of fees, and home visits would greatly improve infant follow up.}, } @article {pmid19604245, year = {2009}, author = {Tamura, N and Hasebe, T and Okada, N and Houjoh, T and Akashi-Tanaka, S and Shimizu, C and Shibata, T and Sasajima, Y and Iwasaki, M and Kinoshita, T}, title = {Tumor histology in lymph vessels and lymph nodes for the accurate prediction of outcome among breast cancer patients treated with neoadjuvant chemotherapy.}, journal = {Cancer science}, volume = {100}, number = {10}, pages = {1823-1833}, doi = {10.1111/j.1349-7006.2009.01264.x}, pmid = {19604245}, issn = {1349-7006}, mesh = {Adult ; Aged ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Lymphatic Vessels/pathology ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/pathology ; }, abstract = {The present study investigated fibrotic foci (FFs), the grading system for lymph vessel tumor emboli (LVTEs), and the histological characteristics of nodal metastatic tumors that were significantly associated with the outcomes of 115 patients with invasive ductal carcinoma (IDC) who had received neoadjuvant chemotherapy. We compared the outcome predictive power of FFs, the grading system for LVTEs, and the histological characteristics of metastatic tumors in lymph nodes with the well-known clinicopathological characteristics of tumor recurrence and tumor-related death in multivariate analyses. The presence of FFs, as assessed by a biopsy performed before neoadjuvant chemotherapy, significantly increased the hazard rates (HRs) for tumor-related death in all the cases and in cases with nodal metastasis. The grading system for LVTEs, which was assessed using surgical specimens obtained after neoadjuvant chemotherapy, was significantly associated with increasing hazard rates (HRs) for tumor recurrence and tumor-related death in all the cases and in cases with nodal metastasis. Moderate to severe stroma in nodal metastatic tumors and five or more mitotic figures in nodal metastatic tumors were significantly associated with elevated HRs for tumor recurrence and tumor-related death among all the cases. These results indicated that FFs, the grading system for LVTEs, and the histological characteristics of tumor cells in lymph nodes play important roles in predicting the tumor progression of IDCs of the breast in patients treated with neoadjuvant chemotherapy.}, } @article {pmid19595209, year = {2009}, author = {Yuan, Z and Qu, X and Zhang, ZT and Li, JS and Teng, CS and Wang, Y}, title = {[Clinical and pathological features of operable breast cancer in women over 65 years].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {47}, number = {7}, pages = {516-518}, pmid = {19595209}, issn = {0529-5815}, mesh = {Aged ; Aged, 80 and over ; *Breast Neoplasms/drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: To study the clinical and pathological characteristics of operable breast cancer in women over 65 years.

METHODS: The data of 95 patients treated from February 2003 to February 2005 were collected, and the clinicopathological characteristics were retrospectively analyzed.

RESULTS: These 95 patients accounted for 26.1% of all female breast cancer patients registered in our hospital in the mean time. Local advanced breast cancer accounted for 74.5% of the patients. The median time from symptom presentation to treatment seeking was 1.2 years. Curative resection was performed in 96 breasts of 94 patients, 71 patients received chemotherapy and 67 received endocrine therapy. Sixty-four cases (67.3%) were confirmed invasive ductal carcinoma. Positive expression of estrogen or progesterone receptor was found in 65 cases (68.4%); overexpression of C-erbB-2 was found in 23.5% of the patients and low level expression of Ki-67 (<30%) was found in 54.1% of the cases, respectively. The 3-year overall survival rate and disease free survival rate was 87.4% and 71.4%, respectively.

CONCLUSIONS: Of the breast cancer in aged women, most are local advanced breast cancer. Breast cancer in the elderly women has distinctive clinicopathological characteristics. Less radical surgery combined with adjuvant chemotherapy and(or) endocrine therapy is feasible treatment.}, } @article {pmid19595156, year = {2009}, author = {Li, YJ and Wen, G and Yang, L}, title = {[Inspection on angiogenesis in malignant transformation of breast tumor by ultrasound contrast and quantitative analysis].}, journal = {Zhonghua yi xue za zhi}, volume = {89}, number = {9}, pages = {587-591}, pmid = {19595156}, issn = {0376-2491}, mesh = {Adult ; Aged ; Area Under Curve ; Breast Neoplasms/*blood supply/*diagnostic imaging/pathology ; Contrast Media/pharmacokinetics ; Female ; Humans ; Middle Aged ; Neovascularization, Pathologic/*diagnostic imaging ; *Ultrasonography, Doppler, Color ; }, abstract = {OBJECTIVE: To study the effects of angiogenesis on tumorigenesis and the progression of breast carcinoma and precancerous lesion.

METHODS: Real time ultrasound contrast enhanced microvascular imaging (MVI) and time-intensity curve quantitative analysis were conducted on 30 normal controls, 30 cases with simple hyperplasia, 30 cases with atypical hyperplasia (AH), 20 cases with intraductal carcinoma in situ, and 50 cases with invasive ductal carcinoma, all female. Specimens of breast tissues were obtained and immunohistochemistry was used to detect the expression of CD34, a marker of vascular endothelial cells, and vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR.

RESULTS: With the progression of malignant transformation of breast tissue, the expression levels of VEGF and Flk-1/KDR increased gradually, the framework of the vessels became disordered, the levels of MVD and the perfusion parameters, such as peak intensity (PI), area under the curve (AUC), and wash-out time (WOT), increased. Obvious changes in these parameters began since the AH stage. There were not significant differences in the PI, AUC, and WOT levels between the groups of AH and in situ cancer, however, the VEGF and Flk-1/KDR levels of the in situ carcinoma group were significantly higher than those of the AH group (both P<0.05).

CONCLUSION: Angiogenesis plays an important role in the development of breast carcinoma. Contrast MVI and the main perfusion parameters reflect the rule of angiogenesis activity changing in different precancerous lesions, and can be used as non-invasive methods to screen high risk population.}, } @article {pmid19584580, year = {2009}, author = {Shah, P and Robbani, I and Shah, O}, title = {Clinicopathological study of male breast carcinoma: 24 years of experience.}, journal = {Annals of Saudi medicine}, volume = {29}, number = {4}, pages = {288-293}, pmid = {19584580}, issn = {0975-4466}, mesh = {Adult ; Aged ; *Breast Neoplasms, Male/epidemiology/pathology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; }, abstract = {BACKGROUND AND OBJECTIVES: Because breast cancer in men is rare, few patients are available for prospective studies. To learn more about its epidemiology, risk factors, clinical features, genetics and pathology in our country, we conducted a retrospective study of all cases seen in recent decades at our institution.

PATIENTS AND METHODS: We identified each case of male breast cancer in the database at the Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India, between the years 1983 to 2007.

RESULTS: We identified only 32 cases of male breast cancer over the 24-year period. Male breast cancer accounted for 32 (2.8%) of 1141 resected breast specimens, which included all breast lesions and 32 (4.1%) of 780 breast cancer cases. Of the 32 cases, 20 (62.5%) had various associated risk factors. Invasive ductal carcinoma was seen in 30 cases (93.7%). Of 20 cases that underwent molecular studies, 16 (80%) patients had estrogen receptor positivity whereas 14 (70%) had progesterone receptor positivity. Six cases (30%) overexpressed HER2 and p53. The BRCA2 mutation was observed in 4 cases (40%) while no patient presented with the BRCA1 mutation.

CONCLUSION: An incidence of 4.1% for male breast cancer indicates that this disease is not as uncommon as presumed in this part of the world. Breast cancer in men seems more frequently to be hormone receptor positive and the BRCA2 mutation confers a significant risk to men.}, } @article {pmid19580844, year = {2009}, author = {Balsamo, M and Zambello, R and Teramo, A and Pedrazzi, M and Sparatore, B and Scordamaglia, F and Pende, D and Mingari, MC and Moretta, L and Moretta, A and Semenzato, G and Vitale, M}, title = {Analysis of NK cell/DC interaction in NK-type lymphoproliferative disease of granular lymphocytes (LDGL): role of DNAM-1 and NKp30.}, journal = {Experimental hematology}, volume = {37}, number = {10}, pages = {1167-1175}, doi = {10.1016/j.exphem.2009.06.010}, pmid = {19580844}, issn = {1873-2399}, mesh = {Adult ; Aged ; Antigens, Differentiation, T-Lymphocyte/*physiology ; Cell Communication ; Cell Differentiation ; Cell Division ; Cells, Cultured/cytology/metabolism ; Dendritic Cells/*pathology ; Female ; HMGB1 Protein/metabolism ; Humans ; Killer Cells, Natural/*pathology ; Leukemia, Large Granular Lymphocytic/metabolism/*pathology ; Male ; Middle Aged ; Natural Cytotoxicity Triggering Receptor 3/*physiology ; }, abstract = {OBJECTIVE: Natural killer (NK) cells and dendritic cells (DC) can give rise to reciprocal functional interactions resulting in promotion of DC maturation, killing of immature DC (iDC), and proliferation of NK cells. In this study, we analyze whether, in NK-lymphoproliferative disease of granular lymphocytes (LDGL) patients, this function could be altered and contribute to the persistence of the disease.

MATERIALS AND METHODS: Freshly isolated peripheral blood NK granular lymphocytes (GL) and NK cell lines derived from 13 different NK-LDGL patients were analyzed in coculture experiments to evaluate their ability to interact with monocyte-derived DCs (Mo-DC).

RESULTS: As compared to NK cells isolated from healthy donors, NK-GLs displayed, in most cases, a reduced capability of promoting Mo-DC maturation and of killing iDC. These findings could be explained, at least in part, by the low expression levels of NKp30: an activating receptor involved in the molecular interactions occurring between NK cells and DC. We also show that, in the presence of DC-derived cytokines such as interleukin-12, in both patients and healthy individuals, DNAM-1 can cooperate with NKp30 to induce NK cells to kill DC, release tumor necrosis factor-alpha, and promote DC maturation. This contribution, however, is not sufficient to compensate for the defect in patients' NK cells.

CONCLUSION: Besides expanding knowledge of the molecular basis of the NK/DC cross-talk, our study demonstrates that NK cells from NK-LDGL patients are impaired in their ability to interact with Mo-DC. The possible relationship between such abnormal NK cell/DC interactions and chronic NK cell proliferation are discussed.}, } @article {pmid19580475, year = {2009}, author = {Cummings, RJ and Mitra, S and Foster, TH and Lord, EM}, title = {Migration of skin dendritic cells in response to ionizing radiation exposure.}, journal = {Radiation research}, volume = {171}, number = {6}, pages = {687-697}, pmid = {19580475}, issn = {0033-7587}, support = {R01 CA028332-24/CA/NCI NIH HHS/United States ; R01 CA028332-28/CA/NCI NIH HHS/United States ; R01 CA068409-14/CA/NCI NIH HHS/United States ; R01 CA028332-27/CA/NCI NIH HHS/United States ; R01 CA028332-29/CA/NCI NIH HHS/United States ; R01 CA028332-21A1/CA/NCI NIH HHS/United States ; R01 CA068409/CA/NCI NIH HHS/United States ; R01 CA068409-07/CA/NCI NIH HHS/United States ; R01 CA028332/CA/NCI NIH HHS/United States ; U19AI067733/AI/NIAID NIH HHS/United States ; R01 CA028332-19/CA/NCI NIH HHS/United States ; R01CA28332/CA/NCI NIH HHS/United States ; CA68409/CA/NCI NIH HHS/United States ; R01 CA068409-05/CA/NCI NIH HHS/United States ; R01 CA028332-22/CA/NCI NIH HHS/United States ; U19 AI067733/AI/NIAID NIH HHS/United States ; R01 CA068409-11/CA/NCI NIH HHS/United States ; R01 CA068409-13A1/CA/NCI NIH HHS/United States ; R01 CA068409-06/CA/NCI NIH HHS/United States ; R01 CA028332-20/CA/NCI NIH HHS/United States ; R01 CA068409-12/CA/NCI NIH HHS/United States ; R01 CA068409-15/CA/NCI NIH HHS/United States ; R01 CA028332-26/CA/NCI NIH HHS/United States ; R01 CA028332-25/CA/NCI NIH HHS/United States ; R01 CA068409-10/CA/NCI NIH HHS/United States ; R01 CA028332-23/CA/NCI NIH HHS/United States ; R01 CA068409-09/CA/NCI NIH HHS/United States ; R01 CA068409-08/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Count ; Cell Movement/physiology/*radiation effects ; Dendritic Cells/metabolism/pathology/*radiation effects ; Dose-Response Relationship, Radiation ; Female ; Fluorescence ; *Gamma Rays ; Histocompatibility Antigens Class II/metabolism ; Interleukin-12/administration & dosage/metabolism ; Langerhans Cells/metabolism/pathology/*radiation effects ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Microscopy, Confocal ; Microscopy, Fluorescence ; Receptors, Interleukin-12/genetics ; Recombinant Proteins/administration & dosage/metabolism ; Skin/immunology/metabolism/radiation effects ; Time Factors ; }, abstract = {We describe an imaging assay that monitors the migration of two unique subsets of immune dendritic cells (DC), interstitial dendritic cells (iDC) and Langerhans cells (LC), found in the dermal and epidermal layers of skin, respectively. Using this assay, we study responses of these cells to ionizing radiation. Results obtained using whole-mount histology and fluorescence microscopy suggest that ionizing radiation triggered the migration of both major histocompatibility complex (MHC) class II(+) iDC and Langerin(+) LC in a dose- and time-dependent manner. Migration appeared to be limited by local administration of recombinant IL-12, a potent immunostimulatory cytokine known to induce DNA repair. Those findings were extended to an in vivo model by injecting fluorescently conjugated anti-MHC class II antibodies intradermally into the ears of live, anesthetized mice and visualizing the DC population in the same ear before and after radiation exposure using confocal microscopy.}, } @article {pmid19576361, year = {2009}, author = {Harmon, WG and Sleeper, LA and Cuniberti, L and Messere, J and Colan, SD and Orav, EJ and Towbin, JA and Wilkinson, JD and Lipshultz, SE}, title = {Treating children with idiopathic dilated cardiomyopathy (from the Pediatric Cardiomyopathy Registry).}, journal = {The American journal of cardiology}, volume = {104}, number = {2}, pages = {281-286}, pmid = {19576361}, issn = {1879-1913}, support = {R01 HL053392/HL/NHLBI NIH HHS/United States ; R01 HL053392-15/HL/NHLBI NIH HHS/United States ; R01 HL53392/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Cardiomyopathy, Dilated/*diagnosis/physiopathology/*therapy ; Cardiotonic Agents/therapeutic use ; Child ; Child, Preschool ; Confidence Intervals ; Female ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Multivariate Analysis ; Odds Ratio ; Prospective Studies ; Registries ; }, abstract = {In 40% of children with symptomatic idiopathic dilated cardiomyopathy (IDC), medical therapy fails within 2 years of diagnosis. Strong evidence-based therapies are not available for these children, and how evidence-based therapies for adults with IDC should be applied to children is unclear. Using data from the National Heart, Lung, and Blood Institute's Pediatric Cardiomyopathy Registry, we compared practice patterns of initial therapies for children with IDC diagnosed from 1990 to 1995 (n = 350) and from 2000 to 2006 (n = 219). At diagnosis, 73% had symptomatic heart failure (HF), and 7% had > or =1 family member with IDC. Anti-HF medications were most commonly prescribed initially. Anti-HF medication use was similar across the 2 periods (84% and 87%, respectively), as was angiotensin-converting enzyme inhibitor use (66% and 70%, respectively). These medications were used more commonly in children with greater left ventricular dilation and poorer left ventricular fractional shortening and functional class (p <0.001). Beta-blocker use was 4% to 18% over the 2 periods. Treatments for pediatric IDC have changed little over the previous 25 years. Anti-HF medications remain the most common treatment, and they are often given to children with asymptomatic left ventricular dysfunction. Children with asymptomatic left ventricular dysfunction are often not offered angiotensin-converting enzyme inhibitors without echocardiographic evidence of advanced disease. In conclusion, therapeutic clinical trials are strongly indicated because practice variation is substantial and medical outcomes in these children have not improved in the previous several decades.}, } @article {pmid19569713, year = {2009}, author = {Lu, WG and Jiang, L and Feng, XL and Lu, TB}, title = {Three-dimensional lanthanide anionic metal-organic frameworks with tunable luminescent properties induced by cation exchange.}, journal = {Inorganic chemistry}, volume = {48}, number = {15}, pages = {6997-6999}, doi = {10.1021/ic900506z}, pmid = {19569713}, issn = {1520-510X}, abstract = {Three 3D lanthanide anionic metal-organic frameworks {K(5)[Ln(5)(IDC)(4)(ox)(4)]} (n) x (20H(2)O)(n) with 1D channels were synthesized under hydrothermal conditions [Ln = Gd (1), Tb (2), and Dy (3)]. The K(+) ions within the 1D channel are easily exchanged with various cations. The emission intensities of Tb(III) in 2 increased significantly upon the addition of Ca(2+) ions, while the introduction of other metal ions caused the intensities to be either unchanged or weakened.}, } @article {pmid19568416, year = {2009}, author = {Nakata, K and Ohuchida, K and Nagai, E and Hayashi, A and Miyasaka, Y and Kayashima, T and Yu, J and Aishima, S and Oda, Y and Mizumoto, K and Tanaka, M and Tsuneyoshi, M}, title = {LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {11}, number = {7}, pages = {712-719}, pmid = {19568416}, issn = {1476-5586}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma in Situ/genetics/metabolism/pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; DNA-Binding Proteins/*genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; LIM Domain Proteins ; Male ; Metalloproteins/*genetics/metabolism ; Middle Aged ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Prognosis ; Proto-Oncogene Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {PURPOSE: LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer.

EXPERIMENTAL DESIGN: We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.

RESULTS: Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results.

CONCLUSIONS: LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer.}, } @article {pmid19568168, year = {2010}, author = {Schorr, MC and Pedrini, JL and Savaris, RF and Zettler, CG}, title = {Are the pure in situ breast ductal carcinomas and those associated with invasive carcinoma the same?.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {18}, number = {1}, pages = {51-54}, doi = {10.1097/PAI.0b013e3181acaded}, pmid = {19568168}, issn = {1533-4058}, mesh = {Adult ; Aged ; Antigens, Neoplasm/*analysis ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal, Breast/*diagnosis/immunology/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Middle Aged ; Neoplasm Invasiveness/*diagnosis/immunology ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis ; Young Adult ; }, abstract = {It has been reported that pure ductal carcinoma in situ of the breast has morphologic differences from the in situ component of the invasive ductal carcinoma, as well estrogen and progesterone receptors expression according to their cytokeratin expression. However, there is no data comparing other tumor markers without using the cytokeratin expression. The objective of this study is to compare the expression of estrogen receptor (ER) and progesterone receptor (PR), HER-2/neu, p53, and Ki67 between pure ductal in situ carcinoma (pDCIS) and the in situ component of the invasive ductal carcinoma (DCIS + IDC) of the breast, and the in situ component to the invasive component of the same tumor (DCIS + IDC). The immunohistochemistry expression of the tumor markers was performed in 45 cases of pDCIS and DCIS + IDC, yielding a total of 90 cases. Statistical analysis was carried out using Fisher exact test, having a P < 0.05, and Kappa index (kappa) to assess intratumoral concordance. In DCIS + IDC, the in situ and invasive components did not show a significant difference and Kappa index (kappa) was high (0.7-1) for positive and negative expression. ER and PR were significantly different between the pDCIS and DCIS + IDC (ER: 86.7 vs. 66.7% P = 0.04; PR: 80% vs. 55.6% P = 0.02). These findings suggest that in situ component of DCIS + IDC and pDCIS are distinct conditions.}, } @article {pmid19567399, year = {2009}, author = {Perrone, G and Altomare, V and Zagami, M and Vulcano, E and Muzii, L and Battista, C and Rabitti, C and Muda, AO}, title = {Breast-like vulvar lesion with concurrent breast cancer: a case report and critical literature review.}, journal = {In vivo (Athens, Greece)}, volume = {23}, number = {4}, pages = {629-634}, pmid = {19567399}, issn = {0258-851X}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*secondary ; Diagnosis, Differential ; Female ; Humans ; Vulvar Neoplasms/*secondary ; }, abstract = {In the current report, we describe an intriguing case of a breast-like cancer lesion located in the vulvar region in a woman lacking a remarkable past medical or family history of breast cancer but with concurrent breast cancer. Consequently, a differential diagnosis between a primary synchronous breast and vulvar cancer or a metastatic breast carcinoma to the vulva is a key point in terms of the clinical approach. In a review of the literature, 39 cases of breast-like cancer lesion have been described: 23 cases of primary infiltrating carcinoma of the vulva and 16 cases of vulvar metastases of breast carcinoma. To the best of our knowledge, this is the first report of a clinically synchronous vulvar metastasis from an invasive ductal carcinoma. The main diagnostic criteria for differential diagnosis between primary or metastatic breast-like vulvar carcinoma are also discussed.}, } @article {pmid19566361, year = {2009}, author = {Alamsamimi, M and Mirkheshti, N and Mohajery, MR and Abdollahi, M}, title = {Bilateral invasive ductal carcinoma in a woman with neurofibromatosis type 1.}, journal = {Archives of Iranian medicine}, volume = {12}, number = {4}, pages = {412-414}, pmid = {19566361}, issn = {1735-3947}, mesh = {Breast Neoplasms/*etiology/pathology/therapy ; Carcinoma, Ductal, Breast/*etiology/pathology/therapy ; Female ; Humans ; Middle Aged ; Neurofibromatosis 1/*complications/pathology ; }, abstract = {A 51-year-old woman with neurofibromatosis type 1 presented to our department for investigation of a left breast lump (50 x 50 x 30 mm); a mass in the right breast (40 x 40 x 20 mm) was also detected on physical examination. The lumps were suspected to be malignant based on physical examination and ultrasonography. Biopsy and frozen sections subsequently confirmed a diagnosis of bilateral invasive ductal carcinoma. A standard bilateral radical mastectomy was performed, followed by postoperative chemoendocrine therapy. Tumor recurrence has not been observed within the first 23 months following the surgery.}, } @article {pmid19565246, year = {2009}, author = {Reiner, CS and Helbich, TH and Rudas, M and Ponhold, L and Riedl, CC and Kropf, N and Fuchsjäger, MH}, title = {Can galactography-guided stereotactic, 11-gauge, vacuum-assisted breast biopsy of intraductal lesions serve as an alternative to surgical biopsy?.}, journal = {European radiology}, volume = {19}, number = {12}, pages = {2878-2885}, pmid = {19565246}, issn = {1432-1084}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle/*methods ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Female ; Humans ; Mammary Glands, Human/*pathology ; Mammography/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; *Stereotaxic Techniques ; Surgery, Computer-Assisted/*methods ; }, abstract = {The purpose of this study was to determine the value of galactography-guided, stereotactic, vacuum-assisted breast biopsy (VABB) for the assessment of intraductal breast lesions and its potential as a therapeutic tool that could eliminate the need for surgical excision. Eighteen patients (median age 64 years, range 37-80) with nipple discharge and galactography-verified intraductal lesions underwent galactography-guided, stereotactic, 11-gauge VABB followed by surgery. Histopathology findings from VABB and subsequent surgery were compared. Underestimation and false-negative rates were assessed. After VABB, histopathology revealed invasive ductal carcinoma (IDC) in three (17%), ductal carcinoma in situ (DCIS) in six (33%), high-risk lesions in six (33%) and benign lesions in three (17%) cases. After surgical biopsy, histopathology confirmed the previously established diagnosis in 11 lesions (61%). The underestimation rate for high-risk lesions and DCIS was 50% (6/12). The false-negative rate was 7% (1/14). Histopathology examination after surgery showed that not a single lesion had been completely removed at VABB. Galactography-guided VABB is a feasible diagnostic tool. However, its value as a therapeutic procedure is limited because of the high number of underestimated and missed lesions and because of the histopathological detection of lesions' remnants in every case. Surgical excision should be the therapeutic gold standard in cases of pathological nipple discharge and galactography abnormalities.}, } @article {pmid19535328, year = {2009}, author = {Xu, M and Bai, L and Gong, Y and Xie, W and Hang, H and Jiang, T}, title = {Structure and functional implications of the human rad9-hus1-rad1 cell cycle checkpoint complex.}, journal = {The Journal of biological chemistry}, volume = {284}, number = {31}, pages = {20457-20461}, pmid = {19535328}, issn = {1083-351X}, mesh = {*Cell Cycle ; Cell Cycle Proteins/*chemistry/*metabolism ; DNA Damage ; Exonucleases/*chemistry/*metabolism ; Humans ; Models, Biological ; Models, Molecular ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; }, abstract = {Cellular DNA lesions are efficiently countered by DNA repair in conjunction with delays in cell cycle progression. Previous studies have demonstrated that Rad9, Hus1, and Rad1 can form a heterotrimeric complex (the 9-1-1 complex) that plays dual roles in cell cycle checkpoint activation and DNA repair in eukaryotic cells. Although the 9-1-1 complex has been proposed to form a toroidal structure similar to proliferating cell nuclear antigen (PCNA), which plays essential roles in DNA replication and repair, the structural basis by which it performs different functions has not been elucidated. Here we report the crystal structure of the human 9-1-1 complex at 3.2 A resolution. The crystal structure, together with biochemical assays, reveals that the interdomain connecting loops (IDC loop) of hRad9, hHus1, and hRad1 are largely divergent, and further cocrystallization study indicates that a PCNA-interacting box (PIP box)-containing peptide derived from hFen1 binds tightly to the interdomain connecting loop of hRad1, providing the molecular basis for the damage repair-specific activity of the 9-1-1 complex in contrast to PCNA. Furthermore, structural comparison with PCNA reveals other unique structural features of the 9-1-1 complex that are proposed to contribute to DNA damage recognition.}, } @article {pmid19521003, year = {2009}, author = {Farquharson, MJ and Al-Ebraheem, A and Geraki, K and Leek, R and Jubb, A and Harris, AL}, title = {Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status.}, journal = {Physics in medicine and biology}, volume = {54}, number = {13}, pages = {4213-4223}, doi = {10.1088/0031-9155/54/13/016}, pmid = {19521003}, issn = {0031-9155}, mesh = {Biomarkers, Tumor/*analysis ; Carcinoma, Ductal, Breast/*chemistry ; Computer Simulation ; Female ; Humans ; *Models, Biological ; Models, Statistical ; Receptors, Estrogen/*analysis ; Statistics as Topic ; Zinc/*analysis ; }, abstract = {Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).}, } @article {pmid19514014, year = {2009}, author = {Barone, P and Antonini, A and Colosimo, C and Marconi, R and Morgante, L and Avarello, TP and Bottacchi, E and Cannas, A and Ceravolo, G and Ceravolo, R and Cicarelli, G and Gaglio, RM and Giglia, RM and Iemolo, F and Manfredi, M and Meco, G and Nicoletti, A and Pederzoli, M and Petrone, A and Pisani, A and Pontieri, FE and Quatrale, R and Ramat, S and Scala, R and Volpe, G and Zappulla, S and Bentivoglio, AR and Stocchi, F and Trianni, G and Dotto, PD and , }, title = {The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {24}, number = {11}, pages = {1641-1649}, doi = {10.1002/mds.22643}, pmid = {19514014}, issn = {1531-8257}, mesh = {Aged ; Antiparkinson Agents/therapeutic use ; Anxiety/epidemiology/etiology/psychology ; Cognition Disorders/epidemiology/etiology/psychology ; Depression/epidemiology/etiology/psychology ; Fatigue/epidemiology/etiology/psychology ; Female ; Gastrointestinal Diseases/epidemiology/etiology/psychology ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Olfaction Disorders/epidemiology/etiology/psychology ; Pain/epidemiology/etiology/psychology ; Parkinson Disease/complications/drug therapy/*psychology ; *Quality of Life ; Sleep Disorders, Intrinsic/epidemiology/etiology/psychology ; Urination Disorders/epidemiology/etiology/psychology ; }, abstract = {We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.}, } @article {pmid19496781, year = {2009}, author = {Garcia-Etienne, CA and Cody Iii, HS and Disa, JJ and Cordeiro, P and Sacchini, V}, title = {Nipple-sparing mastectomy: initial experience at the Memorial Sloan-Kettering Cancer Center and a comprehensive review of literature.}, journal = {The breast journal}, volume = {15}, number = {4}, pages = {440-449}, doi = {10.1111/j.1524-4741.2009.00758.x}, pmid = {19496781}, issn = {1524-4741}, mesh = {Adult ; Breast Neoplasms/pathology/psychology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Mastectomy/*methods ; Medical Records ; Middle Aged ; Nipples/anatomy & histology/*pathology ; Patients/psychology ; Retrospective Studies ; Skin/pathology ; }, abstract = {Success achieved with skin-sparing mastectomy has led surgeons to reconsider the necessity of nipple-areola complex removal. This study reports our short- and mid-term postoperative outcomes with nipple-sparing mastectomy (NSM) and an updated review of reported literature. Data were retrospectively abstracted from medical records at our institution. Patients underwent NSM based on patient preference, oncologic criteria, and cosmesis. A literature review was undertaken through a PUBMED search and selected based on title and abstract relevance. Twenty-five patients underwent 42 NSMs at our institution from July 2000 to October 2005. Patient mean age was 44 years (29-59 years). Indications for mastectomy were: 34 (81%) for prophylaxis, 5 (12%) for invasive ductal carcinoma, 2 (5%) for ductal carcinoma in situ, and 1 (2%) for a malignant phyllodes tumor. One prophylactic mastectomy specimen showed ductal carcinoma in situ in the retroareolar tissue, and the nipple-areola complex was removed at a second operation. Mean tumor size in cases with invasive carcinoma (n = 5) was 1.9 cm (0.7-2.5 cm). All tumors were peripherally located, and no cases showed occult nipple involvement. The nipple-areola complex was entirely preserved in 39 (93%) mastectomies. One nipple-areola complex was surgically removed, and two (5%) cases had partial loss due to infection or ischemia. Cosmetic result from surgeon's assessment was excellent in 30 mastectomies, good in 7, acceptable in 3, and poor in 2, with slight nipple asymmetry in 8 cases. At a median follow-up of 10.5 months (range, 0.4-56.4 months), the 39 nipple-areola complexes were intact and there were no local or systemic recurrences in cases treated for cancer. NSM represented approximately 1% of all mastectomies performed at our institution during the reported period. It was mostly used for prophylaxis and for the treatment of malignant tumors in few selected cases. NSM can be performed with a high success rate of nipple-areola complex preservation. Conclusions about the oncologic safety of this procedure cannot be drawn from our study due to small size series and short follow-up. However, available published data show that NSM can be safely performed for breast cancer treatment in carefully selected cases. Further studies and longer follow-up are necessary to refine selection criteria for NSM.}, } @article {pmid19490469, year = {2009}, author = {Sasaki, Y and Tsuda, H and Ueda, S and Asakawa, H and Seki, K and Murata, T and Kuriki, K and Tamai, S and Matsubara, O}, title = {Histological differences between invasive ductal carcinoma with a large central acellular zone and matrix-producing carcinoma of the breast.}, journal = {Pathology international}, volume = {59}, number = {6}, pages = {390-394}, doi = {10.1111/j.1440-1827.2009.02382.x}, pmid = {19490469}, issn = {1440-1827}, mesh = {Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Extracellular Matrix/metabolism/pathology ; Female ; Humans ; }, abstract = {Carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrix-producing carcinoma (MPC) have been recently noted as basal-like-type breast cancers, but the two entities are often confused. To clarify their histological differences, the histopathological sections of 15 CAC and seven MPC were examined and the following features were compared by reviewing slides: (i) mode of invasion; (ii) alteration of cancer cell adhesion in the transitional area between cellular and acellular zones; (iii) staining of the stromal matrix; (iv) lymphocyte infiltration; and (v) tumor grade. Complete agreement was required between two observers for the assessments of these features. All CAC had relatively sharp margins but showed infiltrative growth accompanied by eosinophilic intercellular matrix. In CAC there was abrupt transition between peripheral cellular and central acellular zones without alteration of cancer cell adhesion. In contrast, all MPC showed expansive growth with a well circumscribed margin, accompanied by basophilic and myxoid intercellular matrix. In MPC there was gradual transition from cellular to acellular areas with gradual loss of cancer cell adhesion. Histological grade 3 and peripheral lymphocyte infiltration were common features. It is suggested that CAC and MPC are histologically distinct entities, and that the aforementioned features are helpful for differential diagnosis.}, } @article {pmid19489267, year = {2009}, author = {Gao, JD and Zhang, BN and Wang, X and Wang, J and Bi, XF}, title = {[Clinicopathological characteristics and prognosis of patients with breast cancer over 65 years of age].}, journal = {Zhonghua yi xue za zhi}, volume = {89}, number = {2}, pages = {83-86}, pmid = {19489267}, issn = {0376-2491}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/*pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {OBJECTIVE: To study clinicopathological characteristics and prognosis of elderly women with breast cancer.

METHODS: The data of 399 patients with breast cancer over 65 years of age was analyzed retrospectively in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1989 to December 2003.

RESULTS: Curative resection was performed for all patients, including modified radical mastectomy 277 (69.4%), radical mastectomy 12 (3.0%), breast-conserving therapy 59 (15.8%), mammectomy 24 (6.0%), breast segmentectomy 25 (6.3%) and breast segmentectomy with sentinel node biopsy 2 (0.5%). Major pathological type was invasive ductal carcinoma (337/399, 85.5%). The positive rates of estrogen receptor (ER) and progesterone receptor (PR) were 71.4% and 69.6%, respectively. The overall 5-and 10- year survival rates were 78.9% and 56.3%, respectively. Univariate analysis showed that ER status, PR status, T stage, lymph node status and histological grade were significant statistically (P < 0.05). The multivariate analysis showed ER status, lymph node status and histological grade were the independent prognostic factors.

CONCLUSION: Elderly women with breast cancer should be given multimodality therapy. Surgery and endocrine therapy are crucial, but the surgical style should be individuation. ER status, lymph node status and histological grade were the independent prognostic factors.}, } @article {pmid19489232, year = {2009}, author = {Zhang, RJ and Niu, Y and Gao, YX}, title = {[Recent advances in studies on in-situ and invasive ductal carcinoma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {1}, pages = {63-65}, pmid = {19489232}, issn = {0529-5807}, mesh = {Aneuploidy ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma in Situ/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; *Cell Movement ; DNA Methylation ; DNA, Neoplasm/genetics ; Female ; Humans ; Membrane Proteins/metabolism ; Neoplasm Invasiveness ; }, } @article {pmid19489222, year = {2009}, author = {Yang, Y and Wei, B and Zhang, Z and Tang, Y and Fu, J and Liao, DY and Li, FY and Bu, H}, title = {[Intralaboratory reproducibility of HER2 testing in breast cancer by immunohistochemistry and comparison of results obtained by different assays].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {38}, number = {1}, pages = {29-34}, pmid = {19489222}, issn = {0529-5807}, mesh = {Antibodies, Monoclonal/metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; Humans ; Immunohistochemistry/*methods ; Receptor, ErbB-2/*metabolism ; Reproducibility of Results ; }, abstract = {OBJECTIVES: To investigate the intralaboratory reproducibility of immunohistochemistry (IHC) testing for HER2 status in breast cancer, and to evaluate the factors which influence the reproducibility. The concordance between monoclonal antibody CB11 and HercepTest was also assessed.

METHODS: HER2 overexpression on paraffin sections from thirty-seven cases of breast invasive ductal carcinoma was evaluated using CB11 and the evaluation procedure had been repeated for five times scored the tests together according to the HercepTest and new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) grading schemes by 2 experienced pathologists together. Reproducibility rates of the five rounds were assessed using Kappa statistic, and the results from two scoring systems were compared. HercepTest kit was applied to the same cases afterward and the results were compared with CB11.

RESULTS: Substantial intralaboratory reproducibility was achieved among 5 rounds tests. Excluding the influence effect of changing antibody lots, the intralaboratory reproducibility was closed to the perfect threshold (Kappa = 0.7858, HercepTest scheme). The results derived from the two grading schemes had an almost perfect agreement (Kappa = 0.8549). The concordance (positive vs. negative) between CB11 and HercepTest was 83.78%.

CONCLUSIONS: Laboratory work with strict supervision and more experience will ensure a reliable testing consistency. Reproducibility analysis could be adopted to evaluate the intralaboratory staining quality on HER2 testing. Different antibody lots bring some influence to the intralaboratory reproducibility, but not significant. CB11 could be accepted to screen HER2 status in routine practice after testing validation.}, } @article {pmid19485975, year = {2009}, author = {Siggins, RW and Bagby, GJ and Molina, P and Dufour, J and Nelson, S and Zhang, P}, title = {Alcohol exposure impairs myeloid dendritic cell function in rhesus macaques.}, journal = {Alcoholism, clinical and experimental research}, volume = {33}, number = {9}, pages = {1524-1531}, pmid = {19485975}, issn = {1530-0277}, support = {P60 AA009803/AA/NIAAA NIH HHS/United States ; AA07577/AA/NIAAA NIH HHS/United States ; R01 AA013543/AA/NIAAA NIH HHS/United States ; R01 AA013543-04S1/AA/NIAAA NIH HHS/United States ; R01 AA011290/AA/NIAAA NIH HHS/United States ; P60 AA009803-16S1/AA/NIAAA NIH HHS/United States ; AA11290/AA/NIAAA NIH HHS/United States ; R01 AA011290-15/AA/NIAAA NIH HHS/United States ; T32 AA007577/AA/NIAAA NIH HHS/United States ; T32 AA007577-09/AA/NIAAA NIH HHS/United States ; R37 AA011290/AA/NIAAA NIH HHS/United States ; AA09803/AA/NIAAA NIH HHS/United States ; P50 AA009803/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow Cells/*drug effects ; Cells, Cultured ; Central Nervous System Depressants/*toxicity ; Dendritic Cells/*drug effects ; Ethanol/*toxicity ; Flow Cytometry ; Hematopoietic Stem Cells/*drug effects ; Macaca mulatta ; Membrane Proteins/biosynthesis ; Monocytes/drug effects ; }, abstract = {BACKGROUND: Alcohol intoxication suppresses both the innate and adaptive immunities. Dendritic cells (DCs) are the major cell type bridging the innate and acquired immune responses. At the present time, the effects of alcohol on DC development in hematopoietic tissues and the functional activities of DCs are incompletely elucidated. This study investigated the impact of chronic alcohol exposure on the alteration of hematopoietic precursor cell and DC populations in the bone marrow and peripheral blood of rhesus macaques.

METHODS: Rhesus macaques were administered alcohol or isocaloric sucrose daily for a period of 3 months through surgically implanted gastric catheters. Peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) were isolated for flow cytometric analysis after 3 months. Monocytes were cultured with human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml) in the absence and presence of alcohol (50 mM). On day 6 of the culture, a cocktail of stimulants including IL-1beta (18 ng), IL-6 (1800 U), TNF-alpha (18 ng), and PGE(2) (1.8 microg) were added to the designated wells for transformation of immature dendritic cells (iDCs) to mature myeloid DCs. The cells were analyzed on day 8 by flow cytometry for expression of DC costimulatory molecule expression.

RESULTS: EtOH-treated animals had significantly lower numbers of myeloid DCs (lineage-HLA-DR+CD11c+CD123-) in both the PBMCs and BMCs compared to controls (5,654 +/- 1,273/10(6) vs. 2,353 +/- 660/10(6) PBMCs and 503 +/- 34 vs. 195 +/- 44/10(6) BMCs). Under culture conditions, the number of lineage-HLA-DR+CD83+ cells was low in control wells (0.38 +/- 0.08%). Alcohol inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in iDC wells (2.30 +/- 0.79% vs. 5.73 +/- 1.40%). Alcohol also inhibited the increase in the number of lineage-HLA-DR+CD83+ cells in mature DC wells (1.23 +/- 0.15% vs. 4.13 +/- 0.62%).

CONCLUSIONS: Chronic EtOH decreases the bone marrow and circulating pools of myeloid DCs. Additionally, EtOH suppresses costimulatory molecule CD83 expression during DC transformation, which may attenuate the ability of DCs to initiate T-cell expansion.}, } @article {pmid19485944, year = {2009}, author = {Kuskunović, S and Radović, S and Dorić, M and Hukić, A and Babić, M and Tomić, I and Selak, I}, title = {Immunohistochemical expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in invasive breast carcinoma.}, journal = {Bosnian journal of basic medical sciences}, volume = {9}, number = {2}, pages = {125-130}, pmid = {19485944}, issn = {1512-8601}, mesh = {Adult ; Aged ; Breast Neoplasms/*chemistry ; Cytoplasm/chemistry ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/analysis ; Tissue Inhibitor of Metalloproteinase-1/*analysis ; }, abstract = {Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010). Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023). Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005). TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.}, } @article {pmid19483464, year = {2009}, author = {Csankovszki, G}, title = {Condensin function in dosage compensation.}, journal = {Epigenetics}, volume = {4}, number = {4}, pages = {212-215}, doi = {10.4161/epi.8957}, pmid = {19483464}, issn = {1559-2308}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics/*physiology ; Animals ; Caenorhabditis elegans/*genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA-Binding Proteins/genetics/*physiology ; *Dosage Compensation, Genetic ; Evolution, Molecular ; Female ; Humans ; Male ; Models, Genetic ; Multiprotein Complexes/genetics/*physiology ; }, abstract = {Dosage compensation is an essential process that equalizes X-linked gene dosage between the sexes. In the worm Caenorhabditis elegans, a complex of proteins called the dosage compensation complex (DCC) binds both X chromosomes in hermaphrodites to downregulate gene expression two-fold and hence to reduce X-linked gene expression levels equal to that in males. Five subunits of the DCC form the condensin I(DC) complex, a homolog of the evolutionarily conserved condensin complex required for chromosome segregation and compaction during mitosis and meiosis. How related complexes can perform such diverse functions remains a mystery. Nevertheless, it is believed that the mitotic and interphase functions of condensin are mechanistically related and understanding one process will reveal new insights into the other. We discuss how during worm dosage compensation a condensin-mediated function may guide the organization of the interphase chromatin fibers, leading to the formation of a repressive nuclear compartment.}, } @article {pmid19483192, year = {2009}, author = {Wang, H and Zhao, A and Chen, L and Zhong, X and Liao, J and Gao, M and Cai, M and Lee, DH and Li, J and Chowdhury, D and Yang, YG and Pfeifer, GP and Yen, Y and Xu, X}, title = {Human RIF1 encodes an anti-apoptotic factor required for DNA repair.}, journal = {Carcinogenesis}, volume = {30}, number = {8}, pages = {1314-1319}, pmid = {19483192}, issn = {1460-2180}, support = {R01CA084469/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/*drug effects ; Blotting, Western ; Breast Neoplasms/drug therapy/metabolism/*pathology ; Camptothecin/therapeutic use ; Carcinoma, Ductal, Breast/drug therapy/metabolism/*pathology ; Cell Differentiation ; Cell Proliferation ; *DNA Breaks, Double-Stranded ; *DNA Repair ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Nuclear Proteins/*physiology ; Nuclear Receptor Co-Repressor 1 ; RNA, Small Interfering/pharmacology ; Repressor Proteins/*physiology ; Signal Transduction/drug effects ; Staurosporine/therapeutic use ; Tumor Cells, Cultured ; }, abstract = {Human Rap1-interacting protein 1 (RIF1) contributes to the ataxia telangiectasia, mutated-mediated DNA damage response against the dexterous effect of DNA lesions and plays a critical role in the S-phase checkpoint. However, the molecular mechanisms by which human RIF1 conquers DNA aberrations remain largely unknown. We here showed that inhibition of RIF1 expression by small interfering RNA led to defective homologous recombination-mediated DNA double-strand break repair and sensitized cancer cells to camptothecin or staurosporine treatment. RIF1 underwent caspase-dependent cleavage upon apoptosis. We further found that RIF1 was highly expressed in human breast tumors, and its expression status was positively correlated with differentiation degrees of invasive ductal carcinoma of the breast. Our results suggest that RIF1 encodes an anti-apoptotic factor required for DNA repair and is a potential target for cancer treatment.}, } @article {pmid19481341, year = {2009}, author = {Beltrán-Heredia, J and Sánchez-Martín, J and Delgado-Regalado, A and Jurado-Bustos, C}, title = {Removal of Alizarin Violet 3R (anthraquinonic dye) from aqueous solutions by natural coagulants.}, journal = {Journal of hazardous materials}, volume = {170}, number = {1}, pages = {43-50}, doi = {10.1016/j.jhazmat.2009.04.131}, pmid = {19481341}, issn = {1873-3336}, mesh = {Anthraquinones/*isolation & purification ; Coloring Agents/isolation & purification ; Hydrogen-Ion Concentration ; Moringa oleifera/chemistry ; Plant Extracts/chemistry ; Plant Proteins/chemistry ; Solutions ; Tannins/chemistry ; Temperature ; Water Pollutants, Chemical/*isolation & purification ; Water Purification/*methods ; }, abstract = {In this paper the ability of two natural products in removing dyes has been tested. After a preliminary screening for dye removal capacity, a tannin-based coagulant called ACQUAPOL C-1 and a vegetal protein extract derived from Moringa oleifera seed have been fully studied. The influence of several parameters such as pH, temperature or initial dye concentration (IDC) have been tested and the behavior of both coagulants has been compared. pH results to be an interesting variable and dye removal decreases as pH increases. This effect is higher in ACQUAPOL C-1 than in M. oleifera seed extract. Temperature seems not to be so affecting parameter, while IDC appears to be a very important variable in q(c) capacity, which is higher as IDC increases. Langmuir isotherm model fits very well in both cases of ACQUAPOL C-1 and M. oleifera seed extract dye removal.}, } @article {pmid19479727, year = {2009}, author = {Marchiò, C and Iravani, M and Natrajan, R and Lambros, MB and Geyer, FC and Savage, K and Parry, S and Tamber, N and Fenwick, K and Mackay, A and Schmitt, FC and Bussolati, G and Ellis, I and Ashworth, A and Sapino, A and Reis-Filho, JS}, title = {Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components.}, journal = {The Journal of pathology}, volume = {218}, number = {3}, pages = {301-315}, doi = {10.1002/path.2572}, pmid = {19479727}, issn = {1096-9896}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Papillary/*genetics/metabolism/pathology ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Female ; Humans ; Immunophenotyping ; Neoplasm Proteins/metabolism ; Neoplasms, Complex and Mixed/*genetics/metabolism/pathology ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Micropapillary carcinomas (MPCs) can present as a rare histological special type of breast cancer; however, this histological type is more frequently found admixed with invasive ductal carcinomas of no special type (IDC-NSTs). We have previously demonstrated that pure MPCs constitute a distinct entity at the morphological and genetic levels. Here, we sought to determine whether mixed MPCs have genomic aberrations similar to those found in pure MPCs, and to investigate whether the distinct morphological components of MPCs harbour different genetic aberrations. Using high-resolution microarray comparative genomic hybridization (aCGH), we profiled a series of 10 MPCs of mixed histology and 20 IDC-NSTs matched for grade and oestrogen receptor (ER) status. In addition, we generated tissue microarrays containing a series of 24 pure and 40 mixed MPCs and performed immunohistochemical analysis with ER, progesterone receptor (PR), Ki-67, HER2, cytokeratin (CK) 5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1 and E-cadherin antibodies. In situ hybridization was employed to evaluate the prevalence of HER2, TOP2A, EGFR, CCND1, MYC and FGFR1 gene amplification. Our results demonstrate that mixed MPCs harbour similar patterns of genomic aberrations and phenotype (82.5% luminal and 17.5% HER2) compared to pure MPCs. A comparison between the distinct morphological components of mixed MPCs in a pairwise fashion revealed that both components harbour strikingly similar genomic profiles. When compared to grade- and ER-matched IDC-NSTs, mixed MPCs significantly more frequently harboured amplification of multiple regions on 8q (adjusted Fisher's p value < 0.05). Furthermore, mixed MPCs displayed higher proliferative rates than grade- and ER-matched IDC-NSTs. Our results suggest that micropapillary differentiation in breast cancer may identify a subgroup of more aggressive ER-positive breast carcinomas, even in those featuring a mixed histology, and that mixed MPCs are more closely related to pure MPCs than to IDC-NSTs.}, } @article {pmid19473551, year = {2009}, author = {Qi, L and Bart, J and Tan, LP and Platteel, I and Sluis, Tv and Huitema, S and Harms, G and Fu, L and Hollema, H and Berg, Av}, title = {Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {163}, pmid = {19473551}, issn = {1471-2407}, mesh = {Apoptosis Regulatory Proteins/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Epithelium/*metabolism ; Female ; *Gene Expression ; Humans ; MicroRNAs/*genetics/metabolism ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*genetics/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Tropomyosin/*genetics/metabolism ; }, abstract = {BACKGROUND: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA.

METHODS: We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry.

RESULTS: Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue.

CONCLUSION: Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.}, } @article {pmid19472358, year = {2009}, author = {Seltzer, S and Aboulhosn, J and Levi, DS}, title = {Use of interlock fibered detachable coils for occlusion of collaterals, coronary artery fistulae, and patent ductus arteriosus.}, journal = {Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions}, volume = {74}, number = {5}, pages = {770-776}, doi = {10.1002/ccd.22092}, pmid = {19472358}, issn = {1522-726X}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *Collateral Circulation ; Coronary Angiography ; *Coronary Circulation ; Coronary Vessel Anomalies/diagnostic imaging/physiopathology/*therapy ; Ductus Arteriosus, Patent/diagnostic imaging/physiopathology/*therapy ; Embolization, Therapeutic/adverse effects/*instrumentation ; Equipment Design ; Female ; Humans ; Infant ; Male ; Retrospective Studies ; Treatment Outcome ; Vascular Fistula/diagnostic imaging/physiopathology/*therapy ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the utility of interlocking detachable coils (IDC) for transcatheter occlusion of vascular communications in congenital heart disease.

BACKGROUND: The IDC can be delivered in a retractable fashion through hydrophilic Renegade microcatheters. They incorporate thrombogenic synthetic fibers and cost less than comparable neurovascular coils. They are ideally suited for use in many forms of congenital heart disease.

METHODS: A retrospective review of all patients catheterized during the initial 18-month period of IDC availability at our institution was performed. Interlock coils were only used if traditional methods could not be used easily and safely. All congenital patients in whom IDC were used are described.

RESULTS: A total of 61 coils were deployed in 17 patients with various vessels not amenable to treatment with conventional coils. Coils were used in aortopulmonary collaterals (n = 7), veno-venous collaterals (n = 9), patent ductus arteriosus (n = 3), and coronary artery fistulae (CAF) (n = 2). Operators were able to control coils and withdraw into the catheter for repositioning without difficulty. Thirteen of 21 vessels demonstrated immediate occlusion. All late angiograms have demonstrated complete occlusion of all vessels, with one exception requiring reintervention. One coil migrated from a large CAF and was easily retrieved with a snare. No serious complications occurred. All patients had an uneventful postcatheterization course.

CONCLUSIONS: Transcatheter vascular coil embolization with IDCs can be performed safely and effectively in a variety of circumstances.}, } @article {pmid19461184, year = {2009}, author = {Sawada, Y and Fujii, T and Takahashi, H and Yokoyama, G and Matsubayashi, RN and Inoue, Y and Uesugi, N and Momosaki, S and Toh, U and Shirouzu, K}, title = {[A case of triple negative chest wall recurrent breast cancer treated with capecitabine and docetaxel combination therapy (XT therapy)].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {5}, pages = {815-817}, pmid = {19461184}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*drug therapy/*pathology/surgery ; Capecitabine ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Docetaxel ; Female ; Fluorouracil/*analogs & derivatives/therapeutic use ; Humans ; Middle Aged ; Positron-Emission Tomography ; Taxoids/*therapeutic use ; Thoracic Neoplasms/blood/*drug therapy/pathology/*secondary ; Thoracic Wall/pathology ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {A 59-year-old woman underwent modified radical mastectomy for left breast cancer 9 years earlier. This time, a chest wall recurrence was found. A chest CT showed a chest wall tumor and lymph node metastases. PET images showed increased uptake in chest wall tumor and lymph nodes. The serum tumor markers have also elevated. Open biopsy of chest wall tumor was performed, and the tumor was diagnosed as invasive ductal carcinoma[ER(-), Pg R (-), HER2 score(0)]. Combination chemotherapy with capecitabine and docetaxel was initiated. After 7 courses of treatment, a marked response has been seen. Capecitabine and docetaxel combination therapy are considered useful for treatment of triple negative recurrent breast cancer.}, } @article {pmid19461183, year = {2009}, author = {Morohashi, S and Morohashi, H and Saito, C and Odagiri, H}, title = {[A case of recurrent breast cancer with liver metastasis responding to exemestane].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {5}, pages = {811-814}, pmid = {19461183}, issn = {0385-0684}, mesh = {Adult ; Androstadienes/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*drug therapy/*pathology/surgery ; Female ; Humans ; Liver Neoplasms/blood/diagnostic imaging/*drug therapy/*secondary ; Recurrence ; Tomography, X-Ray Computed ; }, abstract = {We report a woman in her 30s who developed a right breast tumor 10 years after undergoing mastectomy for invasive ductal carcinoma of the left breast. She underwent modified radical mastectomy for the right breast cancer, which was diagnosed histologically as invasive ductal carcinoma with metastasis to the axillary lymph nodes. Because of the risk of recurrence, she received postoperative systemic adjunctive chemotherapy using CMF, but this had to be withdrawn because of liver toxicity. The patient therefore received hormonal therapy with goserelin and tamoxifen for 24 months. During this period, however, she became menopausal, necessitating withdrawal of the goserelin. After a disease-free interval of 34 months, liver metastasis appeared, and so tamoxifen was changed to exemestane. After 3 months, the metastasis showed a marked response, and this has been subsequently maintained for 48 months. Because the patient's menstrual cycle then returned, goserelin was restarted after consultation with a gynecologist. This case illustrates that exemestane and goserelin combination therapy is effective for recurrent breast cancer.}, } @article {pmid19454615, year = {2009}, author = {Eheman, CR and Shaw, KM and Ryerson, AB and Miller, JW and Ajani, UA and White, MC}, title = {The changing incidence of in situ and invasive ductal and lobular breast carcinomas: United States, 1999-2004.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {18}, number = {6}, pages = {1763-1769}, doi = {10.1158/1055-9965.EPI-08-1082}, pmid = {19454615}, issn = {1538-7755}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma in Situ/*epidemiology/pathology ; Carcinoma, Ductal, Breast/*epidemiology/pathology ; Carcinoma, Lobular/*epidemiology/pathology ; Female ; Humans ; Incidence ; Middle Aged ; Registries ; SEER Program ; United States ; }, abstract = {BACKGROUND: National incidence rates for lobular and ductal breast cancers have not been available previously. Evidence suggests that the increased risk of breast cancer associated with combined hormone replacement therapy use is higher for invasive lobular cancers (ILC) than for invasive ductal cancers (IDC). This study provides U.S. incidence rates for these histologic types for both in situ and invasive cancers and assesses changes in the incidence of these cancers over time.

METHODS: Data for this study included incident ductal and lobular breast cancer cases diagnosed from 1999 through 2004 in central cancer registries in 44 states and the District of Columbia from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program. We estimated incidence per 100,000 women by 10-year age groups, race, and ethnicity. We also assessed the percent change in invasive and in situ cancer incidence over time.

RESULTS: We observed distinct differences in the change of incidence over time between in situ and invasive lobular and ductal breast cancers. The age-adjusted rates of ILC and IDC declined an average of 4.6% and 3.3% per year, respectively. Overall, ILC decreased 20.5% from 1999 to 2004. The patterns of ductal and lobular in situ cancer incidence were not consistent over time, and the total change was negligible.

CONCLUSION: The declines in ILC observed in our study are consistent with a decrease in cancer incidence related to a reduced use of combined hormone replacement therapy. However, other factors could also be responsible for these changes.}, } @article {pmid19448591, year = {2009}, author = {Yeh, IT and Martin, MA and Robetorye, RS and Bolla, AR and McCaskill, C and Shah, RK and Gorre, ME and Mohammed, MS and Gunn, SR}, title = {Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {22}, number = {9}, pages = {1169-1175}, doi = {10.1038/modpathol.2009.78}, pmid = {19448591}, issn = {1530-0285}, support = {P30 CA54174/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Chromosomes, Artificial, Bacterial ; Chromosomes, Human, Pair 17/*genetics ; Comparative Genomic Hybridization/*methods ; Female ; *Gene Dosage ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Reproducibility of Results ; }, abstract = {The HER2 gene is an important prognostic and therapeutic marker in newly diagnosed breast cancer. Currently, HER2 status is most frequently determined by immunohistochemical detection of HER2 protein expression on the cellular membrane surface or by fluorescence in situ hybridization analysis of HER2 gene copy number in fixed tissue using locus-specific probes for the HER2 gene and chromosome 17 centromere. However, these methods are problematic because of issues with intra- and inter-laboratory reproducibility and preanalytic variables, such as fixation time. In addition, the commonly used HER2/chromosome 17 ratio presumes that chromosome 17 polysomy is present when the centromere is amplified, even though analysis of the rest of the chromosome is not included in the assay. In this study, 97 frozen samples of invasive lobular and invasive ductal carcinoma, with known immunohistochemistry and fluorescence in situ hybridization results for HER2, were analyzed by comparative genomic hybridization to a commercially available bacterial artificial chromosome whole-genome array containing 99 probes targeted to chromosome 17 and the HER2/TOP2 amplicon. Results were 97% concordant for HER2 status, meeting the College of American Pathologists/American Society of Clinical Oncology's validation requirements for HER2 testing. Surprisingly, not a single case of complete polysomy 17 was detected even though multiple breast cancer cases showed clear polysomies of other chromosomes. We conclude that array comparative genomic hybridization is an accurate and objective DNA-based alternative for clinical evaluation of HER2 gene copy number, and that polysomy 17 is a rare event in breast cancer.}, } @article {pmid19446418, year = {2010}, author = {Linda, A and Zuiani, C and Girometti, R and Londero, V and Machin, P and Brondani, G and Bazzocchi, M}, title = {Unusual malignant tumors of the breast: MRI features and pathologic correlation.}, journal = {European journal of radiology}, volume = {75}, number = {2}, pages = {178-184}, doi = {10.1016/j.ejrad.2009.04.038}, pmid = {19446418}, issn = {1872-7727}, mesh = {Adenocarcinoma/*diagnosis/pathology ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Carcinoma, Lobular/diagnosis/pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; }, abstract = {Unusual malignant breast tumors are well-differentiated subtypes of invasive ductal carcinoma, including mucinous, tubular, medullary and papillary carcinomas, and account for about 10% of malignant breast tumors. They are increasingly being encountered during magnetic resonance imaging (MRI) examinations of the breast. Therefore, breast radiologists should be aware of their appearance on MRI. This review provides an overview of MRI characteristics of a range of unusual tumors (mucinous carcinoma, medullary carcinoma, tubular carcinoma, intraductal papillary carcinoma, intracystic papillary carcinoma and invasive papillary carcinoma), highlighting specific clues for diagnosis and correlating MRI and pathologic features. Many unusual breast tumors exhibit MRI features similar to those of benign or low suspicious lesions (oval shape, well-defined margins, high signal intensity on T2-weighted images, continuous increase kinetics, i.e. type I dynamic curve), leading to a possible misdiagnosis. Nevertheless, an understanding of pathologic features of these tumors, especially tissue content (mucinous, fibrous) and growth pattern, can help to define some specific clues for their diagnosis.}, } @article {pmid19444935, year = {2009}, author = {Miki, Y and Suzuki, T and Sasano, H}, title = {Intracrinology of sex steroids in ductal carcinoma in situ (DCIS) of human breast: comparison to invasive ductal carcinoma (IDC) and non-neoplastic breast.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {114}, number = {1-2}, pages = {68-71}, doi = {10.1016/j.jsbmb.2008.12.021}, pmid = {19444935}, issn = {1879-1220}, mesh = {17-Hydroxysteroid Dehydrogenases/metabolism ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism ; Androgens/chemistry/*metabolism ; *Breast/anatomy & histology/metabolism/pathology ; *Breast Neoplasms/metabolism/pathology ; *Carcinoma, Ductal/metabolism/pathology ; Estrogens/chemistry/*metabolism ; Female ; Humans ; Isoenzymes/metabolism ; Molecular Structure ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Steryl-Sulfatase/metabolism ; Sulfotransferases/metabolism ; }, abstract = {Sex steroids, including those through intratumoral production in an intracrine manner, play important roles in the development of invasive ductal carcinoma (IDC) of human breast, but biological and/or clinical significance of intratumoral production and metabolism of sex steroids, have remained largely unknown in the ductal carcinoma in situ (DCIS), an important precursor lesion of IDC. We recently examined tissue concentration of estradiol and 5-dihydrotestosterone using liquid chromatography/electrospray tandem mass spectrometry in non-neoplastic breast, DCIS, and IDC tissues. Results of our study suggest that intratumoral concentrations of both estradiol and 5-dihydrotestosterone are increased in DCIS, which is considered due to intratumoral production of these sex steroids. Therefore, both estradiol and 5-dehydrotestosterone are considered to play important roles in the development of DCIS as well as IDC through an intracrine manner. Intratumoral metabolism and synthesis of estrogens and androgens as a result of the interactions of various enzymes are therefore also considered to play important roles in hormone dependent DCIS. Aromatase, which is one of the estrogen synthesis enzymes, plays an important role in intratumoral production of estrogen but other enzymes also play pivotal roles in intratumoral estrogen and androgen productions in human breast carcinoma. Therefore, in this review, we also focused on the importance of key intracrine enzymes such as 17beta-hydroxysteroid dehydrogenases, steroid sulfatase,estrogen sulfotransferase, 5alpha-reductases in both IDC and DCIS.}, } @article {pmid19444926, year = {2009}, author = {Hoshino, Y and Ayuse, T and Kurata, S and Ayuse, T and Schneider, H and Kirkness, JP and Patil, SP and Schwartz, AR and Oi, K}, title = {The compensatory responses to upper airway obstruction in normal subjects under propofol anesthesia.}, journal = {Respiratory physiology & neurobiology}, volume = {166}, number = {1}, pages = {24-31}, pmid = {19444926}, issn = {1569-9048}, support = {K23 HL072126/HL/NHLBI NIH HHS/United States ; K23 HL077137/HL/NHLBI NIH HHS/United States ; HL50381/HL/NHLBI NIH HHS/United States ; HL 72126/HL/NHLBI NIH HHS/United States ; R01 HL050381-15A1/HL/NHLBI NIH HHS/United States ; HL077137/HL/NHLBI NIH HHS/United States ; R01 HL050381/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Airway Obstruction/*physiopathology ; Airway Resistance/*drug effects ; Anesthetics, Intravenous/*pharmacology ; Blood Pressure/drug effects/physiology ; Electromyography/methods ; Female ; Humans ; Male ; Pharynx/physiology ; Positive-Pressure Respiration ; Propofol/*pharmacology ; Respiratory Mechanics/*drug effects ; Respiratory Muscles/innervation ; Time Factors ; Young Adult ; }, abstract = {Upper airway obstruction during sleep can trigger compensatory neuromuscular responses and/or prolong inspiration in order to maintain adequate minute ventilation. The aim of this study was to investigate the strength of these compensatory responses during upper airway obstruction during propofol anesthesia. We assessed respiratory timing and upper airway responses to decreases in nasal pressure in nine propofol anesthetized normal subjects under condition of decreased (passive) and increased (active) neuromuscular activity. Critical closing pressure (PCRIT) and upstream resistance (RUS) were derived from pressure-flow relationships generated from each condition. The inspiratory duty cycle (IDC), maximum inspiratory flow (V1max) and respiratory rate (f) were determined at two levels of mean inspiratory airflow (VI; mild airflow limitation with VI > or = 150 ml s-1; severe airflow limitation with VI < 150 ml s-1). Compared to the passive condition, PCRIT decreased significantly (5.3 +/- 3.8 cm H2O, p < 0.05) and RUS increased (7.4 cm H2O ml-1 s, p < 0.05) in the active condition. The IDC increased progressively and comparably as decreased in both the passive and active conditions (p < 0.05). These findings imply that distinct compensatory mechanisms govern the modulation of respiratory pattern and pharyngeal patency during periods of airway obstruction under propofol anesthesia.}, } @article {pmid19443927, year = {2009}, author = {Moses, Y and Shimshoni, I}, title = {3D shape recovery of smooth surfaces: dropping the fixed-viewpoint assumption.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {31}, number = {7}, pages = {1310-1324}, doi = {10.1109/TPAMI.2008.147}, pmid = {19443927}, issn = {0162-8828}, mesh = {*Algorithms ; *Artificial Intelligence ; Face/*anatomy & histology ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Imaging, Three-Dimensional/*methods ; Pattern Recognition, Automated/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; *Subtraction Technique ; }, abstract = {We present a new method for recovering the 3D shape of a featureless smooth surface from three or more calibrated images illuminated by different light sources (three of them are independent). This method is unique in its ability to handle images taken from unconstrained perspective viewpoints and unconstrained illumination directions. The correspondence between such images is hard to compute and no other known method can handle this problem locally from a small number of images. Our method combines geometric and photometric information in order to recover dense correspondence between the images and accurately computes the 3D shape. Only a single pass starting at one point and local computation are used. This is in contrast to methods that use the occluding contours recovered from many images to initialize and constrain an optimization process. The output of our method can be used to initialize such processes. In the special case of fixed viewpoint, the proposed method becomes a new perspective photometric stereo algorithm. Nevertheless, the introduction of the multiview setup, self-occlusions, and regions close to the occluding boundaries are better handled, and the method is more robust to noise than photometric stereo. Experimental results are presented for simulated and real images.}, } @article {pmid19438749, year = {2009}, author = {Liu, F and Lang, R and Wei, J and Fan, Y and Cui, L and Gu, F and Guo, X and Pringle, GA and Zhang, X and Fu, L}, title = {Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast.}, journal = {Histopathology}, volume = {54}, number = {6}, pages = {741-750}, doi = {10.1111/j.1365-2559.2009.03289.x}, pmid = {19438749}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Carcinoma/metabolism/pathology ; Carcinoma, Papillary/metabolism/*pathology ; Chemokine CXCL12/*genetics/metabolism ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Receptors, CXCR4/*genetics/metabolism ; Tissue Array Analysis ; }, abstract = {AIMS: Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread.

METHODS AND RESULTS: We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes (P < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC (P = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC (P = 0.007) and correlated significantly with lymph node status (P = 0.002), although SDF-1 mRNA was rarely detected by CISH.

CONCLUSIONS: This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC.}, } @article {pmid19414985, year = {2009}, author = {Mohammadizadeh, F and Naimi, A and Rajabi, P and Ghasemibasir, H and Eftekhari, A}, title = {Expression of basal and luminal cytokeratins in breast cancer and their correlation with clinicopathological prognostic variables.}, journal = {Indian journal of medical sciences}, volume = {63}, number = {4}, pages = {152-162}, pmid = {19414985}, issn = {0019-5359}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/diagnosis/*genetics/pathology ; Carcinoma, Ductal/diagnosis/*genetics/pathology ; ErbB Receptors/genetics ; Female ; Gene Expression ; Humans ; Keratin-5/*genetics ; Keratin-6/*genetics ; Keratin-7/*genetics ; Middle Aged ; Phenotype ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; }, abstract = {BACKGROUND: Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer.

OBJECTIVE: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma.

MATERIALS AND METHODS: Sixty-seven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells.

RESULTS: We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression.

CONCLUSION: We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.}, } @article {pmid19412328, year = {2008}, author = {Hershberger, RE and Parks, SB and Kushner, JD and Li, D and Ludwigsen, S and Jakobs, P and Nauman, D and Burgess, D and Partain, J and Litt, M}, title = {Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.}, journal = {Clinical and translational science}, volume = {1}, number = {1}, pages = {21-26}, pmid = {19412328}, issn = {1752-8062}, support = {M01 RR000334-380409/RR/NCRR NIH HHS/United States ; R01 HL058626-08/HL/NHLBI NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; 5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01 HL058626/HL/NHLBI NIH HHS/United States ; M01 RR000334/RR/NCRR NIH HHS/United States ; N01-HV-48194/HV/NHLBI NIH HHS/United States ; }, mesh = {Cardiac Myosins/*genetics ; Cardiomyopathy, Dilated/*genetics ; Connectin ; *DNA Mutational Analysis ; Ethnicity ; Exons ; Family Health ; Humans ; Introns ; LIM Domain Proteins ; Muscle Proteins/*genetics ; *Mutation ; Myosin Heavy Chains/*genetics ; NAV1.5 Voltage-Gated Sodium Channel ; Protein Structure, Tertiary ; Sodium Channels/*genetics ; Troponin T/*genetics ; }, abstract = {BACKGROUND: More than 20 genes have been reported to cause idiopathic and familial dilated cardiomyopathy (IDC/FDC), but the frequency of genetic causation remains poorly understood.

METHODS AND RESULTS: Blood samples were collected and DNA prepared from 313 patients, 183 with FDC and 130 with IDC. Genomic DNA underwent bidirectional sequencing of six genes, and mutation carriers were followed up by evaluation of additional family members. We identified in 36 probands, 31 unique protein-altering variants (11.5% overall) that were not identified in 253 control subjects (506 chromosomes). These included 13 probands (4.2%) with 12 beta-myosin heavy chain (MYH7) mutations, nine probands (2.9%) with six different cardiac troponin T (TNNT2) mutations, eight probands (2.6%) carrying seven different cardiac sodium channel (SCN5A) mutations, three probands (1.0%) with three titin-cap or telethonin (TCAP) mutations, three probands (1.0%) with two LIM domain binding 3 (LDB3) mutations, and one proband (0.3%) with a muscle LIM protein (CSRP3) mutation. Four nucleotide changes did not segregate with phentoype and/or did not alter a conserved amino acid and were therefore considered unlikely to be disease-causing. Mutations in 11 probands were assessed as likely disease-causing, and in 21 probands were considered possibly disease-causing. These 32 probands included 14 of the 130 with IDC (10.8%) and 18 of 183 with FDC (9.8%)

CONCLUSIONS: Mutations of these six genes each account for a small fraction of the genetic cause of FDC/IDC. The frequency of possible or likely disease-causing mutations in these genes is similar for IDC and FDC.}, } @article {pmid19408647, year = {2009}, author = {Salopek, D and Murgić, J and Tomas, D and Bolanca, A and Kusić, Z}, title = {Paget's disease in contralateral breast occuring 11 years after mastectomy for invasive ductal carcinoma.}, journal = {Collegium antropologicum}, volume = {33}, number = {1}, pages = {327-329}, pmid = {19408647}, issn = {0350-6134}, mesh = {Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; Immunohistochemistry ; *Mastectomy ; Paget's Disease, Mammary/*pathology ; Receptor, ErbB-2/analysis ; }, abstract = {Paget's disease of the breast is a rare form of breast cancer and represents only 1% to 4% of all breast cancers. It is characterized by the presence of Paget's cells in the epithelium tissue (in epidermis) and it manifests as a lesion of the nipple. In most cases, Paget's disease is associated with an underlying breast malignancy. Mastectomy has been considered the treatment of choice, but breast conservation is also being explored, in properly selected patients, depending on the underlying malignancy. We report a case of Paget's disease occurring in the contralateral breast 11 years after mastectomy for invasive ductal carcinoma but with no underlying breast malignancy.}, } @article {pmid19404978, year = {2009}, author = {Taylor, K and Rolfe, M and Reynolds, N and Kilanowski, F and Pathania, U and Clarke, D and Yang, D and Oppenheim, J and Samuel, K and Howie, S and Barran, P and Macmillan, D and Campopiano, D and Dorin, J}, title = {Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6.}, journal = {European journal of immunology}, volume = {39}, number = {5}, pages = {1353-1360}, pmid = {19404978}, issn = {1521-4141}, support = {MC_U127527201/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Chemotaxis/*immunology ; Dendritic Cells/*immunology ; Flow Cytometry ; Humans ; Immunity, Innate/*immunology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Receptors, CCR6/*immunology ; Reverse Transcriptase Polymerase Chain Reaction ; beta-Defensins/genetics/*immunology ; }, abstract = {Beta-defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine beta-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. In other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine beta-defensins, defensin-related peptide 1 (Defr1) displays chemoattractant activity for CD4(+) T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1 Y5C) or with only a single cysteine (Defr1-1c(V)) chemoattract CD4(+) T cells with reduced activity, but do not chemoattract DC. Beta-defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of beta-defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6.}, } @article {pmid19403322, year = {2009}, author = {Lapierre-Combes, M and Rousset, J and Combes, E and Chinelatto, S and Dupré, PF and André, V}, title = {[Retrospective study conducted in northern Finistère about the role of breast MRI in normal breast screening, experience in 51 patients].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {37}, number = {5}, pages = {401-409}, doi = {10.1016/j.gyobfe.2009.02.013}, pmid = {19403322}, issn = {1297-9589}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/diagnosis/pathology ; Carcinoma/diagnosis/pathology ; Carcinoma, Ductal/diagnosis/pathology ; Female ; France ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography ; Mass Screening/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVES: To study the role and indications of breast MRI in normal breast screening.

PATIENTS AND METHODS: Retrospective study of 51 patients (mean age of 51 years) conducted in northern Finistère. Each patient had a normal (BI-RADS 1 or 2) breast screening (mammography and echography). Four indications for MRI were chosen: screening of high-risk patients, high-density breasts, radio-clinical discordance, and breasts prostheses. Breast MRI were reviewed according to BI-RADS classification. Abnormalities categorized in BI-RADS 4 or 5 were confirmed histologically.

RESULTS: Thirteen patients underwent histological analysis. Nine invasive carcinomas were identified (six invasive lobular carcinomas (ILC), two mixed carcinomas, one invasive ductal carcinoma). For these patients, the reason for performing MRI was a radio-clinical discordance.

DISCUSSION AND CONCLUSION: The study demonstrates the breast MRI value for radio-clinical discordance and the key role of MRI in diagnostic challenge of ILC. In literature review, MRI has a role even if breast screening is normal: radio-clinical discordance, screening of patients with high-risk, breasts prostheses in certain cases. Breast density comes as an additional criteria to perform this exam.}, } @article {pmid19396698, year = {2009}, author = {Tokyol, C and Ersoz, G and Dilek, FH and Gencer, E and Kosar, MN and Dilek, ON}, title = {Thrombospondin 1 expression and angiogenesis in breast carcinoma and their relation with platelet activity.}, journal = {Upsala journal of medical sciences}, volume = {114}, number = {2}, pages = {108-115}, pmid = {19396698}, issn = {2000-1967}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Platelets/*cytology ; Breast Neoplasms/blood/*metabolism/physiopathology ; Case-Control Studies ; Cyclic GMP/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Immunohistochemistry ; Middle Aged ; *Neovascularization, Pathologic ; Thrombospondin 1/*metabolism ; }, abstract = {This study investigates angiogenesis and the expression of thrombospondin 1 in invasive ductal carcinoma of the breast and their possible relation to platelet counts and platelet activity. The study included 20 cases of invasive ductal carcinoma. Platelet activity was evaluated by determining thromboxane B2 and cyclic guanosine monophosphate (cGMP) levels by enzyme immunoassay (EIA).Thrombospondin (TSP) 1 and CD34 expression was studied immunohistochemically. Mean platelet count of the patient group was significantly greater than the mean platelet count of the control group (P < 0.05). The platelet counts were positively correlated with tumour size (r=0.609; P < 0.01). Platelet counts were higher in the patients who had grade 3 microvessel density (P < 0.05). The mean basal platelet cGMP level in the patient group was significantly lower than it was in the control group (P < 0.05). Focal TSP immunoreactivity was detectable in 5 (20%) cases in the tumour cells, and in 9 (45%) cases in the stroma. We did not find any correlation between TSP-1 staining and angiogenesis, platelet counts, platelet activity, and the histological prognostic parameters. Our study confirms the essential role of platelets in tumour growth and angiogenesis. Decreased levels of cGMP in the patient group may cause platelet hyperreactivity. Although thrombospondin 1 may be upregulated in malignant breast tissue, this is not sufficient for tumour growth and dissemination according to our results.}, } @article {pmid19396029, year = {2009}, author = {Jaafar, H and Mohamad Idris, F and Mohd Nafi, SN}, title = {The association between phenotype and size of breast tumors induced by 1-methyl-1-nitrosourea (MNU) injection in rats.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {15}, number = {5}, pages = {BR129-34}, pmid = {19396029}, issn = {1643-3750}, mesh = {Animals ; Carcinogens/*toxicity ; Female ; Mammary Neoplasms, Experimental/chemically induced/*pathology ; Methylnitrosourea/*toxicity ; Phenotype ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Administration of 1-methyl-1-nitrosourea (MNU) is considered a simple and rapid method for inducing breast tumors in rats. While most studies focus on the time frame of tumor development, there are little data on the development of breast tumor in relation to tumor size. Thus the current study was carried out to analyze the phenotype of MNU-induced tumors in relation to tumor size.

MATERIAL/METHODS: Twenty-one 21-day-old female Sprague Dawley rats were administered intraperitoneally with MNU at a dose of 70 mg/kg body weight. The entire palpable tumor was excised when the tumor size reached the diameters of 4.0+/-0.5 mm, 8.0+/-0.5 mm, 12.0+/-0.5 mm, and 16.0+/-0.5 mm and then subjected to histopathological assessment.

RESULTS: Epithelial inclusion cysts and mammary adenomas made up most of the benign tumors, with four cases occurring together with malignant lesions. Ductal carcinoma in situ was seen in tumor sizes of 4.0+/-0.5 mm or less. Among the malignant tumors, the cribriform type was seen predominantly at tumor sizes of less than 12.0+/-0.5 mm, while those with sizes of 12.0+/-0.5 mm or greater were of papillary type. Infiltrating ductal carcinoma-no special type (IDC-NST) commonly seen in humans was also observed at tumor sizes greater than 12.0+/-0.5 mm.

CONCLUSIONS: The tumors were found to be mainly of malignant type and the histological features of the induced tumors underwent changes as the tumor grew in size.}, } @article {pmid19393583, year = {2009}, author = {Celis, JE and Cabezón, T and Moreira, JM and Gromov, P and Gromova, I and Timmermans-Wielenga, V and Iwase, T and Akiyama, F and Honma, N and Rank, F}, title = {Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort.}, journal = {Molecular oncology}, volume = {3}, number = {3}, pages = {220-237}, pmid = {19393583}, issn = {1878-0261}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apocrine Glands/*metabolism/pathology ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/*biosynthesis ; Retrospective Studies ; }, abstract = {Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3-4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available for their diagnosis and no unequivocal information as to their prognosis. In an effort to address these concerns we have been using protein expression profiling technologies in combination with mass spectrometry and immunohistochemistry (IHC) to discover specific biomarkers that could allow us to molecularly characterize these lesions as well as to dissect some of the steps in the processes underlying breast apocrine metaplasia and development of precancerous apocrine lesions. Establishing these apocrine-specific markers as best practice for the routine pathology evaluation of breast cancer, however, will require their validation in large cohorts of patients. Towards this goal we have composed a panel of antibodies against components of an apocrine protein signature that includes probes against the apocrine-specific markers 15-prostaglandin dehydrogenase (15-PGDH), and acyl-CoA synthetase medium-chain family member 1 (ACSM1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERα, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well-defined cohort consisting of 14 apocrine ductal carcinoma in situ (ADCIS), and 33 IACs diagnosed at the Cancer Institute Hospital, Tokyo between 1997 and 2001. Samples were originally classified on the basis of cellular morphology with all cases having more than 90% of the tumour cells exhibiting cytological features typical of apocrine cells. Using the expression of 15-PGDH and/or ACSM1 as the main criterion, but taking into account the expression of other markers, we were able to identify unambiguously 13 out of 14 ADCIS (92.9%) and 20 out of 33 (60.6%) IAC samples, respectively, as being of apocrine origin. Our results demonstrate that IACs correspond to a distinct, even if heterogeneous, molecular subgroup of breast carcinomas that can be readily identified in an unbiased way using a combination of markers that recapitulate the phenotype of apocrine sweat glands (15-PGDH(+), ACSM1(+), AR(+), CD24(+), ERα(-), PgR(-), Bcl-2(-), and GATA-3(-)). These results pave the way for addressing issues such as prognosis of IACs, patient stratification for targeted therapeutics, as well as research strategies for identifying novel therapeutic targets for developing new cancer therapies.}, } @article {pmid19393357, year = {2009}, author = {Taras, AR and Hendrickson, NA and Pugliese, MS and Lowe, KA and Atwood, M and Beatty, JD}, title = {Intraoperative evaluation of sentinel lymph nodes in invasive lobular carcinoma of the breast.}, journal = {American journal of surgery}, volume = {197}, number = {5}, pages = {643-6; discussion 646-7}, doi = {10.1016/j.amjsurg.2008.12.019}, pmid = {19393357}, issn = {1879-1883}, mesh = {Aged ; Axilla ; Breast Neoplasms/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Lobular/pathology/surgery ; Female ; Humans ; Intraoperative Period ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasms, Hormone-Dependent/pathology/surgery ; Registries ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: In breast cancer treatment, sentinel lymph node (SLN) evaluation is used to identify patients who may benefit from axillary lymph node dissection (ALND). Intraoperative evaluation (IE) of SLNs facilitates immediate ALND. Controversy exists regarding the accuracy of intraoperative SLN evaluation for patients with invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC).

METHODS: Using breast cancer registry data from January 2003 to March 2008, the intraoperative SLN evaluation of 66 ILC and 810 IDC patients was compared to the final SLN pathology result and to the performance of ALND.

RESULTS: In ILC, the sensitivities of IE for isolated tumor cells (.2 mm and 2.0 mm, N1a-3a, n = 21) were 0%, 17%, and 71%, respectively. The specificity was 100%. IE identified 16/27 (59%) of SLN-positive (N1mi, N1a-3a) axillae, resulting in synchronous ALND. Delayed ALND for false negative IEs (11/27, 41%) occurred in 7/11 patients (64%). In IDC, the sensitivities of IE for N0(i+) (n = 60), N1mi (n = 75), and N1a-3a (n = 129) metastases were 0%, 7%, and 71%, respectively. The specificity was 99.6%. IE identified 97/204 (48%) of SLN-positive (N1mi, N1a-3a) axillae, resulting in synchronous ALND. Delayed ALND for false negative IEs (107/204, 52%) occurred in 38/107 patients (36%).

CONCLUSIONS: Sensitivity and specificity of intraoperative SLN evaluation is very similar in ILC and IDC patients. Intraoperative SLN evaluation facilitated synchronous ALND in concordance with recommended practice guidelines.}, } @article {pmid19391212, year = {2009}, author = {Pai, RK and West, RB}, title = {MOC-31 exhibits superior reactivity compared with Ber-EP4 in invasive lobular and ductal carcinoma of the breast: a tissue microarray study.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {17}, number = {3}, pages = {202-206}, doi = {10.1097/pai.0b013e31818c0f42}, pmid = {19391212}, issn = {1533-4058}, mesh = {Antibodies/immunology ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/pathology ; Cell Adhesion Molecules/*metabolism ; Diagnosis, Differential ; Epithelial Cell Adhesion Molecule ; Female ; Humans ; Tissue Array Analysis ; }, abstract = {Distinguishing between reactive mesothelial proliferations and adenocarcinoma is often very difficult. Ancillary studies, in particular immunohistochemistry, are often critical in detecting malignant epithelial cells, especially in serous effusion specimens. MOC-31 and Ber-EP4 are antibodies which target the epithelial cell adhesion molecule (Ep-CAM, TACSTD1) expressed in epithelial cells, and both are useful in distinguishing metastatic adenocarcinoma from reactive mesothelial cells. However, the reactivity of MOC-31 and Ber-EP4 with breast carcinoma, one of the more common carcinomas involving serous effusions, has not been extensively studied. We analyzed the immunohistochemical expression of MOC-31 and Ber-EP4 using tissue microarrays containing invasive ductal carcinoma (191 cases), invasive lobular carcinoma (44 cases), and 102 other carcinoma types comprising primary carcinomas of lung, gynecologic tract, pancreas, colon, gastric, esophageal, prostate, head and neck, hepatic, and renal origin. For MOC-31, 184 of 191 (96%) invasive ductal carcinomas and 39 of 44 (89%) invasive lobular carcinomas exhibited diffuse positive staining. In contrast, for Ber-EP4, 121 of 183 (66%) invasive ductal carcinomas and 11 of 40 (27.5%) invasive lobular carcinomas exhibited diffuse positive staining. With the exception of 1 case of esophageal adenocarcinoma, all other adenocarcinomas (86 of 87 cases) exhibited diffuse staining with both Ber-EP4 and MOC-31. MOC-31 and Ber-EP4 exhibited identical staining with all other carcinoma types. Our findings indicate that MOC-31 is superior to Ber-EP4 in detecting both invasive lobular and ductal carcinoma of the breast.}, } @article {pmid19386432, year = {2009}, author = {Liu, GF and Yang, Q and Haffty, BG and Moran, MS}, title = {Clinical-pathologic features and long-term outcomes of tubular carcinoma of the breast compared with invasive ductal carcinoma treated with breast conservation therapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {75}, number = {5}, pages = {1304-1308}, doi = {10.1016/j.ijrobp.2008.12.070}, pmid = {19386432}, issn = {1879-355X}, mesh = {Adenocarcinoma/*drug therapy/mortality/pathology/*radiotherapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*drug therapy/mortality/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology/*radiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate our institutional experience of treating tubular carcinoma of the breast (TC) and invasive ductal carcinoma (IDC) with conservative surgery and radiation therapy, to compare clinical-pathologic features and long-term outcomes.

METHODS AND MATERIALS: A review of our institution's tumor registry from 1975 to 2007, followed by a central pathology review of available slides, yielded 71 cases of Stage I/II TC and 2,238 cases of Stage I/II IDC treated with breast conservation therapy. Clinical-pathologic features and outcomes were analyzed by subtype to detect significant differences.

RESULTS: The median follow-up was 7 years. The TC cohort presented more frequently with pT1 disease (97% vs. 80%, p = 0.0007), pN0 disease (95% vs. 74%, p = 0.0004), hormone-receptor positivity (ER+, 89% vs. 62%, p = 0.0001; PR+, 81% vs. 52%, p = 0.0001), and HER-2 negativity (89% vs. 71%, p = 0.04). Clinical outcomes also favored the TC cohort, with lower rates of breast cancer-related death (1% vs. 10%; p = 0.0109) and distant metastasis (1% vs. 13%; p = 0.0028) and higher rates of 10-year overall (90% vs. 80%; p = 0.033), cause-specific (99% vs. 86%; p = 0.011), and disease-free (99% vs. 82%; p = 0.003) survival. There was a nonsignificant trend toward improved breast cancer relapse-free survival for the TC cohort (95% vs. 87%; p = 0.062) but no difference in nodal relapse-free survival or contralateral breast cancer relapse-free survival (all p values >0.05) between the cohorts.

CONCLUSION: Our institutional experience suggests that TC, when compared with IDC, is associated with more favorable clinical-pathologic features and comparable, if not superior, outcomes after breast conservation therapy, suggesting the appropriateness of a conservative approach to this rare subtype.}, } @article {pmid19384208, year = {2009}, author = {Badjatia, N and Strongilis, E and Prescutti, M and Fernandez, L and Fernandez, A and Buitrago, M and Schmidt, JM and Mayer, SA}, title = {Metabolic benefits of surface counter warming during therapeutic temperature modulation.}, journal = {Critical care medicine}, volume = {37}, number = {6}, pages = {1893-1897}, doi = {10.1097/CCM.0b013e31819fffd3}, pmid = {19384208}, issn = {1530-0293}, support = {GRANT KL2 RR024157/RR/NCRR NIH HHS/United States ; }, mesh = {Brain Injuries/complications/metabolism/therapy ; Calorimetry, Indirect ; *Energy Metabolism ; Female ; *Heating ; Humans ; Hyperthermia, Induced/*methods ; Hypothermia/etiology/*metabolism/*therapy ; Hypothermia, Induced/adverse effects ; Male ; Middle Aged ; Prospective Studies ; *Shivering ; Skin ; }, abstract = {OBJECTIVE: To determine the impact of counter warming (CW) with an air circulating blanket on shivering and metabolic profile during therapeutic temperature modulation (TTM).

DESIGN: A prospective observational study.

SETTING: An 18-bed neurologic intensive care unit.

PATIENTS: Fifty mechanically ventilated patients with brain injury undergoing TTM with automated surface and intravascular devices.

INTERVENTIONS: Fifty indirect calorimetry (IDC) measurements with and without CW during TTM.

MEASUREMENTS AND MAIN RESULTS: IDC was continuously performed for 10-15 minutes at baseline with CW (phase I), off CW (phase II), and again after the return of CW (phase III). Shivering severity during each phase was scored on a scale of 0-3 using the Bedside Shivering Assessment Scale (BSAS). Resting energy expenditure (REE), oxygen consumption, and carbon dioxide production were determined by IDC; 56% were women, with mean age 61 +/- 15 years. At the time of IDC, 72% of patients had signs of shivering (BSAS >0). All measures of basal metabolism increased after removal of the air warming blanket (from phases I and II); REE increased by 27% and oxygen consumption by 29% (both p < 0.002). A one-point increase in baseline BSAS was noted in 55% (n = 23/42) of patients from phase I to phase II. In a multivariate analysis, sedative use (p = 0.03), baseline moderate to severe shivering (p = 0.04), and lower serum magnesium levels (p = 0.01) were associated with greater increases in REE between phase I and phase II of CW. Phase III of CW was associated with a reversal in the increases in all metabolic variables.

CONCLUSIONS: Surface CW provides beneficial control of shivering and improves the metabolic profile during TTM.}, } @article {pmid19384070, year = {2009}, author = {Cangelosi, JJ and Nash, JW and Prieto, VG and Ivan, D}, title = {Cutaneous adnexal tumor with an unusual presentation--discussion of a potential diagnostic pitfall.}, journal = {The American Journal of dermatopathology}, volume = {31}, number = {3}, pages = {278-281}, doi = {10.1097/DAD.0b013e31819ddccf}, pmid = {19384070}, issn = {1533-0311}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/secondary/surgery ; Carcinoma, Ductal, Breast/secondary/surgery ; Cell Differentiation ; Diagnosis, Differential ; Diagnostic Errors/*prevention & control ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Adnexal and Skin Appendage/chemistry/*pathology/therapy ; *Neoplasms, Second Primary ; Skin Neoplasms/chemistry/*pathology/therapy ; }, abstract = {The clinical presentation of skin adnexal tumors is nonspecific, and histologically; the differential diagnosis between primary cutaneous adnexal malignant carcinomas and metastatic tumors with a visceral origin can be challenging. We report a patient with history of invasive ductal carcinoma of the breast who presented with a 1-cm erythematous palpable lesion on her right calf. The biopsy showed an intradermal proliferation of malignant epithelioid cells with ductal differentiation, histologically compatible with metastatic breast carcinoma. However, the tumor cells labeled strongly and diffusely not only for pancytokeratin and cytokeratin (CK7) but also with p63 and CK5/6; carcinoembryonic antigen highlighted the ductal structures. No labeling was seen for mammoglobin, estrogen/progesterone, Her2-neu, S-100 protein, CK20, thyroid transcription factor-1 (TTF-1), and CDX-2. Based on the p63 and CK5/6 positivity, the differential diagnosis also included the possibility of a primary adnexal neoplasm and a complete excision was advised. The reexcision specimen revealed residual infiltrating dermal tumor and an overlying intraepithelial component with marked cytologic atypia and focal duct formation, diagnostic of a primary cutaneous adnexal tumor with ductal differentiation (porocarcinoma). Immunohistochemical studies (like p63 and CK5/6) can help to differentiate a primary cutaneous neoplasm from a metastatic lesion. This discrimination is of a paramount importance because a diagnostic error can result in profound implications for patient's assumed prognosis and subsequently applied therapy.}, } @article {pmid19383825, year = {2009}, author = {Suzuki, J and Chen, YY and Scott, GK and Devries, S and Chin, K and Benz, CC and Waldman, FM and Hwang, ES}, title = {Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {15}, number = {9}, pages = {3163-3171}, pmid = {19383825}, issn = {1078-0432}, support = {K23 CA097181-05/CA/NCI NIH HHS/United States ; K23 CA097181/CA/NCI NIH HHS/United States ; CA367763/CA/NCI NIH HHS/United States ; P50 CA058207-159011/CA/NCI NIH HHS/United States ; K23 CA0977181-01A10/CA/NCI NIH HHS/United States ; P50 CA58207/CA/NCI NIH HHS/United States ; P50 CA058207/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Adult ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/enzymology/pathology ; Disease Progression ; Female ; Histone Deacetylase 1 ; Histone Deacetylase 2 ; Histone Deacetylase 6 ; Histone Deacetylases/*metabolism ; Histones/*metabolism ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Phenotype ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Repressor Proteins/*metabolism ; Tubulin/*metabolism ; Tumor Cells, Cultured ; }, abstract = {PURPOSE: Excess histone deacetylase (HDAC) activity can induce hypoacetylation of histone and nonhistone protein substrates, altering gene expression patterns and cell behavior potentially associated with malignant transformation. However, HDAC expression and protein acetylation have not been studied in the context of breast cancer progression.

EXPERIMENTAL DESIGN: We assessed expression levels of acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in 22 reduction mammoplasties and in 58 specimens with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Differences among groups were tested for significance using nonparametric tests.

RESULTS: From normal epithelium to DCIS, there was a marked reduction in histone acetylation (P < 0.0001). Most cases showed similar levels of acetylation in DCIS and IDC, although some showed further reduction of ac-H4 and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also significantly reduced but by a smaller magnitude. Greater reductions of H4 acetylation and HDAC1 levels were observed from normal to DCIS in estrogen receptor-negative compared with estrogen receptor-positive, and in high-grade compared with non-high-grade tumors.

CONCLUSION: Overall, there was a global pattern of hypoacetylation associated with progression from normal to DCIS to IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and IDC could be an early measure of HDAC inhibitor activity.}, } @article {pmid19366057, year = {2009}, author = {Liu, ZB and Wu, J and Ping, B and Feng, LQ and Di, GH and Lu, JS and Shen, KW and Shen, ZZ and Shaol, ZM}, title = {Basal cytokeratin expression in relation to immunohistochemical and clinical characterization in breast cancer patients with triple negative phenotype.}, journal = {Tumori}, volume = {95}, number = {1}, pages = {53-62}, doi = {10.1177/030089160909500110}, pmid = {19366057}, issn = {0300-8916}, mesh = {Age Factors ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/*mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Keratin-17/*biosynthesis ; Keratin-5/*biosynthesis ; Keratin-6/*biosynthesis ; Lymphatic Metastasis/pathology ; Menopause ; Neoplasm Staging ; Phenotype ; }, abstract = {AIMS AND BACKGROUND: To evaluate the immunohistochemical characterization of CK5/6 and CK17 and whether the expression level of the two markers was correlated with clinical outcome or pathological feature in triple negative (ER-, PR-, HER-2-) patients with breast cancer.

METHODS AND STUDY DESIGN: We carried out an immunohistochemical assay for CK5/6 and CK17 markers on formalin-fixed invasive carcinoma samples from 112 patients who were diagnosed between 2000 and 2002. All of them had an immunohistochemical triple negative status and follow-up information available.

RESULTS: Of the 112 patients characterized by triple negative immunohistochemical status, 82 (73.2%) were disease free with no relapse or metastasis. In total, CK5/6 and CK17 were both determined positive in 33.9% (38/112) of the 112 tumor samples, and 46.4% (52/112) were regarded as positive for CK5/6 or CK17. The Kaplan-Meier curve showed that positive staining for CK5/6, CK17, or CK which means CK5/6 positive or CK17 positive, was associated with worse disease-free survival (P = 0.020, P = 0.032, P = 0.003), and positive staining for CK5/6 or CK was associated with worse overall survival (P = 0.027, P = 0.015). When we considered 91 patients whose pathological type was invasive ductal carcinoma, we found that there was also an association between CK5/6 or CK17 immunostaining and high grade (P = 0.030). In addition, these two markers were also associated with axillary lymph node status (P = 0.044). The Cox regression multiple-factor analysis showed that pathological stage, grade and expression of CK were the factors affecting both disease-free and overall survival, whereas age and menopausal status were independent factors affecting disease-free and overall survival, respectively. CONCLUSIONS; Positive staining for CK5/6 or CK17 was associated with a worse prognosis, high tumor grade and positive axillary lymph nodes.}, } @article {pmid19351366, year = {2009}, author = {Koo, JS and Jung, W}, title = {Xanthogranulomatous mastitis: clinicopathology and pathological implications.}, journal = {Pathology international}, volume = {59}, number = {4}, pages = {234-240}, doi = {10.1111/j.1440-1827.2009.02356.x}, pmid = {19351366}, issn = {1440-1827}, mesh = {Adult ; Aged ; Breast Neoplasms/complications ; Carcinoma in Situ/complications ; Carcinoma, Ductal, Breast/complications ; Female ; Granuloma/complications/metabolism/*pathology ; Humans ; Immunohistochemistry ; Mastitis/metabolism/*pathology ; Middle Aged ; Xanthomatosis/complications/metabolism/*pathology ; }, abstract = {Xanthogranulomatous inflammation is an uncommon finding in the breast. Sixteen cases of xanthogranulomatous mastitis were reviewed to determine the characteristic clinicopathological features. Xanthogranulomatous mastitis involved foamy histiocyte clusters interspersed with inflammatory cells. Foamy histiocytes were bland with small pyknotic nuclei. Xanthogranulomatous mastitis was associated with fat necrosis in five cases (31%), multinucleated giant-cell reactions in six cases (38%), and cholesterol crystals in five cases (31%). In three cases (19%), xanthogranulomatous mastitis coincided with ductal carcinoma in situ or invasive ductal carcinoma. Duct ectasia with foamy histiocyte aggregates were noted in five cases (31%). It is suggested that the etiology of xanthogranulomatous mastitis is obstruction and rupture of the ectatic duct with foamy histiocyte aggregates. In breast core biopsy, granular cell tumor and invasive carcinoma such as histiocytoid carcinoma and lipid-rich carcinoma could demonstrate similar pathological features to xanthogranulomatous mastitis. In conclusion, xanthogranulomatous mastitis could be encountered in breast core biopsy and surgical excision tissue. Diagnosis of xanthogranulomatous mastitis can be made by excluding other diseases that elicit xanthogranulomatous inflammation in the breast. In breast core biopsy, xanthogranulomatous mastitis could be distinguished from granular cell tumor, histiocytoid carcinoma and lipid-rich carcinoma by using cytokeratin and histiocytic marker such as alpha1-anti-trypsin and CD68 stain.}, } @article {pmid19349195, year = {2009}, author = {Li, ZD and Wu, Y and Bao, YL and Yu, CL and Guan, LL and Wang, YZ and Meng, XY and Li, YX}, title = {Identification and characterization of human ARIP2 and its relation to breast cancer.}, journal = {Cytokine}, volume = {46}, number = {2}, pages = {251-259}, doi = {10.1016/j.cyto.2009.02.009}, pmid = {19349195}, issn = {1096-0023}, mesh = {Activin Receptors, Type II/genetics/*metabolism ; Activins/genetics/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Protein Isoforms/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; Transcription, Genetic ; Two-Hybrid System Techniques ; }, abstract = {Activin, a member of the TGF-beta superfamily, inhibits the proliferation of breast cancer cells. Activin interacts with its type I and type II receptors to induce phosphorylation of intracellular signaling molecules known as Smads. Previous studies showed that mouse ARIP2 can reduce activin signaling by interacting with activin type II receptors (ActRIIs); however, the activity of ARIP2 in breast cancer is still unclear. In this study, we used RT-PCR to obtain a human homologue of mouse ARIP2, human activin receptor-interacting protein 2 (hARIP2). Like murine ARIP2, hARIP2 has a PDZ domain in its NH2-terminal region and can interact specifically with ActRIIs. Overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human breast adenocarcinoma MCF-7 cells and MDA-MB-231 cells. However, down-regulation of hARIP2 expression by RNAi enhanced activin-induced transcriptional activity and reduced cell proliferation and colony formation. Immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant breast tissues such as simple carcinoma, invasive ductal carcinoma and mucinous adenocarcinoma than in benign hyperplasia or fibroadenoma cases. These results suggest that hARIP2 is a putative growth-promoting factor involved in breast tumorigenesis and tumor development.}, } @article {pmid19345064, year = {2009}, author = {Meluzin, J and Spinarova, L and Hude, P and Krejci, J and Poloczkova, H and Podrouzkova, H and Pesl, M and Orban, M and Dusek, L and Korinek, J}, title = {Left ventricular mechanics in idiopathic dilated cardiomyopathy: systolic-diastolic coupling and torsion.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {22}, number = {5}, pages = {486-493}, doi = {10.1016/j.echo.2009.02.022}, pmid = {19345064}, issn = {1097-6795}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*diagnostic imaging ; Echocardiography, Doppler/*methods ; Elasticity Imaging Techniques/*methods ; Female ; Humans ; Male ; Middle Aged ; Torsion Abnormality/complications/*diagnostic imaging ; Ventricular Dysfunction, Left/complications/*diagnostic imaging ; }, abstract = {BACKGROUND: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized.

METHODS: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls.

RESULTS: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation.

CONCLUSION: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC.}, } @article {pmid19344495, year = {2009}, author = {Schedin, P and Borges, V}, title = {Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women's breast cancer.}, journal = {Breast cancer research : BCR}, volume = {11}, number = {2}, pages = {102}, pmid = {19344495}, issn = {1465-542X}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*pathology ; Disease Progression ; Epithelial Cells/pathology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Neoplasm Invasiveness ; Stromal Cells/*pathology ; }, abstract = {Gene expression profiling was performed on laser captured breast stroma and epithelium obtained from 14 breast cancer patients. As with breast epithelium, of the stromal gene expression changes observed between normal tissue and invasive ductal carcinoma, greater than 90% occurred early, at the normal to ductal carcinoma in situ transition. Only 10% of stromal and 0% of epithelial genes were differentially regulated between non-invasive ductal carcinoma in situ and invasive disease. These data suggest that the majority of gene expression changes required for transformation occur early, prior to histological evidence of an invasive phenotype, the stroma cooperates closely with epithelium in this transformation, and for acquisition of the invasive phenotype, the stroma is dominant over the epithelium.}, } @article {pmid19339694, year = {2009}, author = {Salogni, L and Musso, T and Bosisio, D and Mirolo, M and Jala, VR and Haribabu, B and Locati, M and Sozzani, S}, title = {Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14.}, journal = {Blood}, volume = {113}, number = {23}, pages = {5848-5856}, doi = {10.1182/blood-2008-12-194597}, pmid = {19339694}, issn = {1528-0020}, mesh = {Activins/*pharmacology ; Animals ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CXCL12/*metabolism ; Chemokines, CXC/*metabolism ; Dendritic Cells/*cytology/drug effects/*metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism ; Humans ; Mice ; Time Factors ; Up-Regulation ; }, abstract = {Activin A is a dimeric protein, member of the transforming growth factor (TGF)-beta family that plays a crucial role in wound repair and in fetal tolerance. Emerging evidence also proposes activin A as a key mediator in inflammation. This study reports that activin A induces the directional migration of immature myeloid dendritic cells (iDCs) through the activation of ALK4 and ActRIIA receptor chains. Conversely, activin A was not active on plasmacytoid dendritic cells (DCs) or mature myeloid DCs. iDC migration to activin A was phosphatidylinositol 3-kinase gamma-dependent, Bordetella pertussis toxin- and cycloheximide-sensitive, and was inhibited by M3, a viral-encoded chemokine-binding protein. In a real-time video microscopy-based migration assay, activin A induced polarization of iDCs, but not migration. These characteristics clearly differentiated the chemotactic activities of activin A from TGF-beta and classic chemokines. By the use of combined pharmacologic and low-density microarray analysis, it was possible to define that activin-A-induced migration depends on the selective and polarized release of 2 chemokines, namely CXC chemokine ligands 12 and 14. This study extends the proinflammatory role of activin A to DC recruitment and provides a cautionary message about the reliability of the in vitro chemotaxis assays in discriminating direct versus indirect chemotactic agonists.}, } @article {pmid19333539, year = {2009}, author = {Naito, Y and Eriguchi, N and Kume, T and Naito, M and Nishimura, M and Ohdo, M and Itai, N and Hayashida, S and Naito, H and Arikawa, S and Ureshino, H and Yasumoto, M and Kusano, H and Yano, H}, title = {Multi-centric pancreatic cancer without PanIN lesion.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {16}, number = {5}, pages = {699-703}, doi = {10.1007/s00534-009-0065-y}, pmid = {19333539}, issn = {1436-0691}, mesh = {Aged ; Biopsy, Needle ; Carcinoma, Pancreatic Ductal/diagnosis/*pathology/surgery ; Diagnostic Imaging/methods ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Liver Neoplasms/diagnosis/surgery ; Magnetic Resonance Imaging ; Male ; Neoplasm Invasiveness/*pathology ; Neoplasms, Multiple Primary/diagnosis/*pathology/surgery ; Pancreatectomy/methods ; Pancreatic Ducts/*pathology/surgery ; Pancreatic Neoplasms/diagnosis/*pathology/surgery ; Risk Assessment ; Splenectomy/methods ; Tomography, X-Ray Computed ; Treatment Outcome ; Ultrasonography, Doppler ; }, abstract = {The patient was a 67-year-old man under follow-up after gastric cancer surgery. An abdominal CT scan performed 1 year earlier had shown an approximately 14-mm hypovascular mass in the pancreatic body; however, he did not consent to treatment and was followed up for 1 year. A blood workup showed that the fasting blood glucose level, which had been within normal limits, was elevated to 174 mg/dl (normal, 70-109 mg/dl), and the HbA1c level was 12.0% (normal, 4.3-5.8%). Abdominal CT revealed an approximately 20-mm mass in the pancreatic body and an approximately 12-mm mass in the pancreatic tail, and magnetic resonance imaging cholangiopancreatography (MRCP) showed discontinuity of the main pancreatic duct (MPD). Since these findings led to the suspicion of invasive ductal carcinoma (IDC) of the pancreas developing in the pancreatic body and tail, we performed distal pancreatectomy with splenectomy. Histologically, IDCs were observed in the pancreatic body and tail. However, PanIN was not observed in the MPD between the two carcinomas. They were diagnosed as independent invasive ductal carcinomas of the pancreas.}, } @article {pmid19332930, year = {2009}, author = {Pervatikar, SK and Rao, R and Dinesh, US and Parameswaraiah, S}, title = {Large mammary hamartoma with focal invasive ductal carcinoma.}, journal = {Indian journal of pathology & microbiology}, volume = {52}, number = {2}, pages = {249-251}, doi = {10.4103/0377-4929.48935}, pmid = {19332930}, issn = {0974-5130}, mesh = {Adult ; Breast Neoplasms/*diagnosis/*pathology/surgery ; Carcinoma, Ductal/*complications/*diagnosis/pathology/surgery ; Female ; Hamartoma/*complications/*diagnosis/pathology/surgery ; Humans ; Mastectomy ; }, abstract = {Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.}, } @article {pmid19318578, year = {2009}, author = {Neal, CL and Yao, J and Yang, W and Zhou, X and Nguyen, NT and Lu, J and Danes, CG and Guo, H and Lan, KH and Ensor, J and Hittelman, W and Hung, MC and Yu, D}, title = {14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival.}, journal = {Cancer research}, volume = {69}, number = {8}, pages = {3425-3432}, pmid = {19318578}, issn = {1538-7445}, support = {R01 CA109570-02/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA109570-05/CA/NCI NIH HHS/United States ; P01 CA099031-010004/CA/NCI NIH HHS/United States ; R01-CA109570/CA/NCI NIH HHS/United States ; P50 CA116199/CA/NCI NIH HHS/United States ; R01 CA109570-03/CA/NCI NIH HHS/United States ; P50 CA116199-040004/CA/NCI NIH HHS/United States ; P01 CA099031/CA/NCI NIH HHS/United States ; P01-CA099031/CA/NCI NIH HHS/United States ; R01-CA119127/CA/NCI NIH HHS/United States ; R01 CA109570-01/CA/NCI NIH HHS/United States ; P50-CA116199/CA/NCI NIH HHS/United States ; R01 CA109570-04/CA/NCI NIH HHS/United States ; R01 CA109570/CA/NCI NIH HHS/United States ; P30-CA 16672/CA/NCI NIH HHS/United States ; }, mesh = {14-3-3 Proteins/*biosynthesis/genetics ; Apoptosis/physiology ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Adhesion/physiology ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Cell Survival/physiology ; Female ; Gene Amplification ; Humans ; Mitochondria/genetics/metabolism ; Neoplasm Recurrence, Local/genetics/*metabolism/pathology ; Prognosis ; Risk Factors ; }, abstract = {The ubiquitously expressed 14-3-3 proteins are involved in numerous important cellular functions. The loss of 14-3-3sigma is a common event in breast cancer; however, the role of other 14-3-3s in breast cancer is unclear. Recently, we found that 14-3-3zeta overexpression occurs in early stage breast diseases and contributes to transformation of human mammary epithelial cells. Here, we show that 14-3-3zeta overexpression also persisted in invasive ductal carcinoma and contributed to the further progression of breast cancer. To examine the clinical effect of 14-3-3zeta overexpression in advanced stage breast cancer, we performed immunohistochemical analysis of 14-3-3zeta expression in primary breast carcinomas. 14-3-3zeta overexpression occurred in 42% of breast tumors and was determined to be an independent prognostic factor for reduced disease-free survival. 14-3-3zeta overexpression combined with ErbB2 overexpression and positive lymph node status identified a subgroup of patients at high risk for developing distant metastasis. To investigate whether 14-3-3zeta overexpression causally promotes breast cancer progression, we overexpressed 14-3-3zeta by stable transfection or reduced 14-3-3zeta expression by siRNA in cancer cell lines. Increased 14-3-3zeta expression enhanced anchorage-independent growth and inhibited stress-induced apoptosis, whereas down-regulation of 14-3-3zeta reduced anchorage-independent growth and sensitized cells to stress-induced apoptosis via the mitochondrial apoptotic pathway. Transient blockade of 14-3-3zeta expression by siRNA in cancer cells effectively reduced the onset and growth of tumor xenografts in vivo. Therefore, 14-3-3zeta overexpression is a novel molecular marker for disease recurrence in breast cancer patients and may serve as an effective therapeutic target in patients whose tumors overexpress 14-3-3zeta.}, } @article {pmid19317888, year = {2009}, author = {Horvath, JW and Barnett, GE and Jimenez, RE and Young, DC and Povoski, SP}, title = {Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma.}, journal = {World journal of surgical oncology}, volume = {7}, number = {}, pages = {34}, pmid = {19317888}, issn = {1477-7819}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; *Frozen Sections ; Humans ; Middle Aged ; Sensitivity and Specificity ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC) versus that of invasive ductal carcinoma (IDC) has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC.

METHODS: We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program) from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed.

RESULTS: No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385), specificity (100% vs. 100%), accuracy (86% vs. 92%, P = 0.172), false negative rate (33% vs. 25%, P = 0.385), negative predictive value (81% vs. 89%, P = 0.158), and positive predictive value (100% vs. 100%) for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC.

CONCLUSION: Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis of all SLNs during breast cancer surgery in patients with ILC should remain the standard of care in order to reduce the risk of the need of a later, separate axillary lymph node dissection.}, } @article {pmid19304743, year = {2009}, author = {Chae, BJ and Bae, JS and Lee, A and Park, WC and Seo, YJ and Song, BJ and Kim, JS and Jung, SS}, title = {p53 as a specific prognostic factor in triple-negative breast cancer.}, journal = {Japanese journal of clinical oncology}, volume = {39}, number = {4}, pages = {217-224}, doi = {10.1093/jjco/hyp007}, pmid = {19304743}, issn = {1465-3621}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/drug therapy/*genetics/mortality ; Carcinoma, Ductal/drug therapy/*genetics/mortality/secondary ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Epirubicin/administration & dosage ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {OBJECTIVE: A recent suggestion is that the predictive value of a single biomarker may rely on the genetic background on the tumor and that different breast cancer subgroups may have different predictive markers of response to chemotherapy. The prognostic value of p53 in the outcome of adjuvant anthracycline-containing chemotherapy was evaluated according to molecular subclasses defined using the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2.

METHODS: Subjects were patients (n = 135) with invasive ductal carcinoma treated with adjuvant anthracycline-based chemotherapy between 1994 and 2000 in our hospital. Clinico-pathological features were reviewed by retrospective examination of medical records.

RESULTS: Overall survival rate was not independently predictive by p53 status (P = 0.182). However, in triple-negative cases, there was statistically significant survival difference (P = 0.034) and no statistically significant difference (P = 0.783) in non-triple-negative cases by p53 status. In the Cox proportional hazard analysis, p53 was also strongly predictive for relapse-free survival (P = 0.013) and overall survival (P = 0.049) in triple-negative patients.

CONCLUSIONS: p53 status could be a specific prognostic factor in triple-negative breast cancer patients treated by adjuvant anthracycline-based regimen. When p53 is positive in triple-negative breast cancer, we could expect poor survival, prompting aggressive or alternative treatment.}, } @article {pmid19295274, year = {2009}, author = {Rai, Y and Sagara, Y and Ooi, Y and Sagara, Y and Sagara, Y and Baba, S and Tamada, S and Matsuyama, Y and Ando, M}, title = {[Preoperative therapy using trastuzumab and weekly paclitaxel in a stage IIIB inoperable locally advanced HER2- positive breast cancer with complete pathologic response].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {36}, number = {3}, pages = {471-473}, pmid = {19295274}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*immunology/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/immunology/*therapeutic use ; Breast Neoplasms/*drug therapy/immunology/metabolism/*pathology ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy ; Middle Aged ; Neoplasm Staging ; Paclitaxel/*therapeutic use ; Receptor, ErbB-2/*metabolism ; Trastuzumab ; Treatment Outcome ; }, abstract = {A 63-year-old woman had a 12 cm tumor on her right breast with broad skin redness, satellite lesions and 8 cm ipsilateral lymph nodes swelling(T4bN2aM0, Stage IIIB). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor(ER-, PgR-)and overexpression of HER2 (HercepTest 3+). She was treated with weekly paclitaxel(80 mg/m(2), 4 administrations with a week rest)and a com- bination with weekly trastuzumab(initially 4 mg/kg followed by 2 mg/kg every week, totally 11 administrations). After 3courses of administration, the breast tumor, skin redness and axillary swelling were completely disappeared(clinical complete response), then mastectomy with axillary dissection was performed. Histopathology of the breast and lymph nodes showed complete disappear of invasive cancer cells with only 2x1 mm residue of ductal component(pCR, grade 3, DC+). We conclude that the combination of weekly paclitaxel and trastuzumab is a promising neoadjuvant therapy regimen for HER2 positive, ER-negative breast cancer.}, } @article {pmid19294389, year = {2010}, author = {Natalin, R and Reis, LO and Alpendre, C and Ikari, LY and Prudente, A and D'Ancona, CA}, title = {Triple therapy in refractory detrusor overactivity: a preliminary study.}, journal = {World journal of urology}, volume = {28}, number = {1}, pages = {79-85}, pmid = {19294389}, issn = {1433-8726}, mesh = {Adolescent ; Adrenergic alpha-Antagonists/*therapeutic use ; Adult ; Aged ; Antidepressive Agents, Tricyclic/*therapeutic use ; Child ; Doxazosin/*therapeutic use ; Drug Synergism ; Drug Therapy, Combination ; Female ; Humans ; Imipramine/*therapeutic use ; Male ; Mandelic Acids/*therapeutic use ; Middle Aged ; Muscarinic Antagonists/*therapeutic use ; Prospective Studies ; Urinary Bladder, Overactive/*drug therapy ; Young Adult ; }, abstract = {PURPOSE: To evaluate in a prospective study the impact of the "three-drug therapy" (antimuscarinic, alpha-blocker and tricyclic antidepressants) on the treatment of refractory detrusor overactivity (DO).

METHODS: Data from 27 consented patients with refractory DO were available for study. They were asked to complete a daily urinary chart and underwent urodynamic evaluation (UD) before and 60 days after treatment. Response to treatment was considered the presence of one or less involuntary detrusor contractions (IDC) on post-treatment UD. Statistical analysis was performed with Fisher and Mann-Whitney tests, besides Spearman's correlation. P values <0.05 were considered significant.

RESULTS: The mean follow-up was 15 months. The comparison of the daily urinary chart before and after treatment showed significant increase on bladder capacity and decreases on urgency, urge-incontinence and frequency. Objective data from UD showed that the mean maximum bladder capacity (MBC) ranged from 200 to 300 mL (P < 0.001) with treatment. The same trend was observed with the other UD variables. When compared to baseline, the questionnaire OAB-v8 showed significant improvement (P < 0.01). Main side effects comprised dry mouth and constipation (40%), with average scores of 5.16 and 3.08, respectively (visual scale from 0 to 10).

CONCLUSIONS: Triple therapy may be an effective, easily employed and well-tolerated option to refractory DO treatment. More studies are necessary to achieve more consistent data on the matter.}, } @article {pmid19294006, year = {2009}, author = {Williams, SL and Birdsong, GG and Cohen, C and Siddiqui, MT}, title = {Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations.}, journal = {International journal of clinical and experimental pathology}, volume = {2}, number = {5}, pages = {476-480}, pmid = {19294006}, issn = {1936-2625}, abstract = {Fine needle aspiration (FNA) is a rapid tool for detection of breast carcinomas. Evaluation of estrogen and progesterone receptors (ER, PR) and HER2 expression by immunohistochemistry (IHC) are routinely performed in breast carcinomas. Formalin fixation of tissue for a minimum of 6 hours, and for HER2 not more than 48 hours is the current recommended practice. In this retrospective study, we compared ER, PR and HER2 expression in breast carcinomas using archival ethanol-fixed FNA cell block with formalin fixed resection tissue block preparations. 34 archival breast carcinoma FNA cell blocks of primary origin with subsequent resection tissue blocks were identified retrospectively. All 34 cases were diagnosed as invasive ductal carcinoma. Cases with neoadjuvant or adjuvant chemotherapy were excluded. Cell blocks were initially fixed in 50% ethanol (4-12 hrs), followed by formalin fixation (minimum 6 hrs). Tissue blocks were formalin-fixed within 4-8 hrs for 6-48 hrs. ER, PR, and HER2 IHC results on the cell blocks and tissue blocks were compared. Alcohol fixed cell block samples for detection of ER and PR by IHC show good agreement with tissue block samples and are therefore a reliable method (weighted Kappa of 0.773 and 0.785, respectively) to triage patients for hormonal treatment. However, HER2 results show only moderate agreement with a weighted kappa of 0.571. The increase in discrepant results may be due to ethanol fixation which results in false positive increased HER2 expression. These results demonstrate the importance of adherence to the College of American Pathologists/ASCO guidelines for HER2 IHC.}, } @article {pmid19293840, year = {2009}, author = {Møller, DV and Andersen, PS and Hedley, P and Ersbøll, MK and Bundgaard, H and Moolman-Smook, J and Christiansen, M and Køber, L}, title = {The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of human genetics : EJHG}, volume = {17}, number = {10}, pages = {1241-1249}, pmid = {19293840}, issn = {1476-5438}, mesh = {Adult ; Amino Acid Sequence ; Cardiomyopathy, Dilated/*genetics ; Cohort Studies ; Denmark ; Echocardiography/methods ; Electrophoresis, Capillary/methods ; Female ; Humans ; Male ; Molecular Sequence Data ; *Mutation ; Pedigree ; Phenotype ; Polymorphism, Single-Stranded Conformational ; Sarcomeres/*genetics/*metabolism ; Sequence Analysis, DNA ; }, abstract = {We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease.}, } @article {pmid19293058, year = {2009}, author = {Broco, S and Bonito, N and Jacinto, P and Sousa, G and Gervásio, H}, title = {Primary non-Hodgkin lymphoma and invasive ductal carcinoma in the same breast: a rare case report.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {11}, number = {3}, pages = {186-188}, pmid = {19293058}, issn = {1699-048X}, mesh = {Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Lymphoma, Non-Hodgkin/diagnosis/*pathology ; }, abstract = {Primary lymphoma of the breast is an unusual clinical entity. The coexistence in the same breast of an invasive ductal carcinoma is even rarer. We report a 69-year old woman referred for further evaluation of a palpable mass in her right breast. She was diagnosed and treated for simultaneous primary lymphoma and invasive ductal carcinoma. Primary breast lymphoma should always be considered in the differential diagnosis of breast masses. The presence of both malignancies presents a challenge in treatment decisions.}, } @article {pmid19292803, year = {2009}, author = {Ling, H and Liu, GY and Lu, JS and Love, S and Zhang, JX and Xu, XL and Xu, WP and Shen, KW and Shen, ZZ and Shao, ZM}, title = {Fiberoptic ductoscopy-guided intraductal biopsy improve the diagnosis of nipple discharge.}, journal = {The breast journal}, volume = {15}, number = {2}, pages = {168-175}, doi = {10.1111/j.1524-4741.2009.00692.x}, pmid = {19292803}, issn = {1524-4741}, support = {N02-CO-41101/CO/NCI NIH HHS/United States ; }, mesh = {Biopsy/methods ; Breast Diseases/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Female ; *Fiber Optic Technology/instrumentation/methods ; Humans ; Hyperplasia/pathology ; Nipples/metabolism/*pathology ; Papilloma/pathology/surgery ; }, abstract = {Fiberoptic ductoscopy (FDS)-guided intraductal biopsy is a minimally invasive technique developed to obtain pathologic diagnoses for patients with spontaneous nipple discharge. We performed biopsies of 53 intraductal lesions from March 2006 to April 2007 followed by surgical microdochectomy. FDS-guided intraductal biopsy was shown to be a minimally invasive, safe, and convenient technique with a high ability (90.6%) to get adequate samples. Twenty-seven solitary papillomas, 12 multiple intraductal papilloma, five ductal hyperplasia, three ductal carcinoma in situ, and one invasive ductal carcinoma were diagnosed. Compared with conventional microdochectomy, FDS-guided intraductal biopsy can significantly increase the detection rate of solitary papilloma (40.7% versus 92.6%, p < 0.05). It should be a routine procedure after intraductal lesion found by screening FDS. Since it would underestimate all multiple intraductal papilloma and some (50%) cancer, microdochectomy is inevitable if biopsies show atypical ductal hyperplasia.}, } @article {pmid19288296, year = {2009}, author = {Guttmann-Steinmetz, S and Gadow, KD and Devincent, CJ}, title = {Oppositional defiant and conduct disorder behaviors in boys with autism spectrum disorder with and without attention-deficit hyperactivity disorder versus several comparison samples.}, journal = {Journal of autism and developmental disorders}, volume = {39}, number = {7}, pages = {976-985}, pmid = {19288296}, issn = {1573-3432}, support = {MH 45358/MH/NIMH NIH HHS/United States ; }, mesh = {Attention Deficit Disorder with Hyperactivity/diagnosis/*epidemiology/*psychology ; Attention Deficit and Disruptive Behavior Disorders/diagnosis/epidemiology/psychology ; Autistic Disorder/diagnosis/*epidemiology/*psychology ; Child ; Comorbidity ; Conduct Disorder/diagnosis/epidemiology/psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Israel/epidemiology ; Male ; Parents ; Psychiatric Status Rating Scales ; Schools ; Severity of Illness Index ; Tic Disorders/diagnosis/*epidemiology/*psychology ; }, abstract = {We compared disruptive behaviors in boys with either autism spectrum disorder (ASD) plus ADHD (n = 74), chronic multiple tic disorder plus ADHD (n = 47), ADHD Only (n = 59), or ASD Only (n = 107). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 including parent- (n = 168) and teacher-rated (n = 173) community controls. Parents rated children in the three ADHD groups comparably for each symptom of oppositional defiant disorder (ODD) and conduct disorder. Teacher ratings indicated that the ASD + ADHD group evidenced a unique pattern of ODD symptom severity, differentiating them from the other ADHD groups, and from the ASD Only group. The clinical features of ASD appear to influence co-morbid, DSM-IV-defined ODD, with implications for nosology.}, } @article {pmid19287511, year = {2009}, author = {Pavicic, WH and Laguens, M and Richard, SM}, title = {Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {15}, number = {5-6}, pages = {160-165}, pmid = {19287511}, issn = {1528-3658}, mesh = {Arylamine N-Acetyltransferase/*genetics ; Breast Neoplasms/*genetics ; DNA, Mitochondrial/genetics ; *Genetic Predisposition to Disease ; Genome, Mitochondrial/*genetics ; *Genomic Instability ; Genotype ; Glutathione Transferase/*genetics ; Humans ; Polymorphism, Genetic/genetics ; }, abstract = {The aim of this study was to determine the existence of association between the genetic polymorphisms of metabolizing genes GSTM-1, GSTT-1, and NAT-2, and the presence of mitochondrial genome instability (mtGI) in breast cancer cases. Ninety-four pairs of tumoral/nontumoral breast cancer samples were analyzed. Our samples showed 40.42% of mtGI by analysis of two D-loop region markers, a (CA)n mtMS starting at the 514-bp position, and four informative MnlI sites between the 16,108-16,420-bp. GSTM-1 null genotype has shown a significant association with mtGI presence (chi(2) = 7.62; P = 0.006) in breast cancer cases; moreover, these genotypes also are related to an increased risk for mtDNA damage (odds ratio [OR] = 3.71 [1.41-9.88]; 95% Cornfield confidence interval [CI]). These results suggest that the absence of GSTM-1 enzymatic activity favors chemical actions in damaging the mtDNA. Analysis of GSTT-1 and NAT-2 polymorphisms showed no association with mtGI (chi(2) = 0.03; P = 0.87 and chi(2) = 2.76; P = 0.09, respectively). The analysis of invasive breast cancer cases showed mtGI in 74.36% of ILC cases (29 of 39 samples), and in only 18.75% (9 out of 48) IDC cases; this result suggests a possible relation between mtDNA mutations and variations in molecular pathways of tumor development.}, } @article {pmid19283332, year = {2009}, author = {Plehn, G and Vormbrock, J and Lefringhausen, L and van Bracht, M and Plehn, A and Butz, T and Trappe, HJ and Meissner, A}, title = {Prevalence of ventricular discordance and its relation to functional capacity in idiopathic dilated cardiomyopathy.}, journal = {Clinical research in cardiology : official journal of the German Cardiac Society}, volume = {98}, number = {6}, pages = {371-378}, pmid = {19283332}, issn = {1861-0692}, mesh = {Cardiomyopathy, Dilated/*diagnosis/*epidemiology ; Comorbidity ; Female ; Germany/epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Assessment ; Risk Factors ; Ventricular Dysfunction, Left/*diagnosis/*epidemiology ; }, abstract = {INTRODUCTION: Although left ventricular (LV) dilatation is the most distinguishing morphologic feature of idiopathic dilated cardiomyopathy (IDC), right ventricular (RV) dilatation may variably contribute to total cardiac enlargement. The prevalence and functional importance of the relative degree of left and right ventricular dilatation has not been comprehensively studied using cardiac magnetic resonance imaging (MRI).

METHODS: Our prospective study included 58 consecutive IDC patients with a LV ejection fraction <40% and NYHA functional class > or =2. MRI was performed with a 1.5 Tesla scanner for RV and LV dimensional and functional analysis. Cardiopulmonary exercise testing was used for evaluation of exercise capacity. Patients were grouped into tertiles based on the distribution of LV end-diastolic volume.

RESULTS: Compared to control subjects a considerable heterogeneity in the relative degree of left and right ventricular dilatation was noted in IDC patients. Within the entire patient group, a strong correlation between the degree of ventricular volume discordance and the extent of LV enlargement was observed (r = 0.8; P < 0.001). Tertile analysis revealed that the LV/RV volume ratio significantly differed in the three subgroups of patients (1.0 +/- 0.3 vs. 1.5 +/- 0.4 vs. 2.1 +/- 0.9; P < 0.001). Only weak correlations between MRI data and patients' functional capacity were found. LV ejection fraction was identified as the only independent predictor of maximum oxygen consumption in our setting.

CONCLUSION: In IDC patients the degree of ventricular volume discordance is strongly related to the extent of left ventricular enlargement. However, comprehensive biventricular assessment of cardiac function by MRI adds little to our understanding of the cardiac mechanisms limiting exercise tolerance when compared to exclusive left ventricular measurements.}, } @article {pmid19282847, year = {2009}, author = {Ilett, EJ and Prestwich, RJ and Kottke, T and Errington, F and Thompson, JM and Harrington, KJ and Pandha, HS and Coffey, M and Selby, PJ and Vile, RG and Melcher, AA}, title = {Dendritic cells and T cells deliver oncolytic reovirus for tumour killing despite pre-existing anti-viral immunity.}, journal = {Gene therapy}, volume = {16}, number = {5}, pages = {689-699}, pmid = {19282847}, issn = {1476-5462}, support = {R01 CA107082/CA/NCI NIH HHS/United States ; R01 CA175386/CA/NCI NIH HHS/United States ; R01130878//PHS HHS/United States ; CA RO1107082-02/CA/NCI NIH HHS/United States ; R01 CA130878/CA/NCI NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Cell Death ; Cytotoxicity, Immunologic ; Dendritic Cells/*transplantation ; Lymph Nodes/virology ; Lymphatic Metastasis ; Melanoma, Experimental/immunology/pathology/*secondary/*therapy ; Mice ; Mice, Inbred C57BL ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/*immunology ; Reoviridae/immunology/isolation & purification ; T-Lymphocytes/*transplantation ; Treatment Outcome ; Tumor Cells, Cultured ; Viral Load ; }, abstract = {Reovirus is a naturally occurring oncolytic virus currently in early clinical trials. However, the rapid induction of neutralizing antibodies represents a major obstacle to successful systemic delivery. This study addresses, for the first time, the ability of cellular carriers in the form of T cells and dendritic cells (DC) to protect reovirus from systemic neutralization. In addition, the ability of these cellular carriers to manipulate the subsequent balance of anti-viral versus anti-tumour immune response is explored. Reovirus, either neat or loaded onto DC or T cells, was delivered intravenously into reovirus-naive or reovirus-immune C57Bl/6 mice bearing lymph node B16tk melanoma metastases. Three and 10 days after treatment, reovirus delivery, carrier cell trafficking, metastatic clearance and priming of anti-tumour/anti-viral immunity were assessed. In naive mice, reovirus delivered either neat or through cell carriage was detectable in the tumour-draining lymph nodes 3 days after treatment, though complete clearance of metastases was only obtained when the virus was delivered on T cells or mature DC (mDC); neat reovirus or loaded immature DC (iDC) gave only partial early tumour clearance. Furthermore, only T cells carrying reovirus generated anti-tumour immune responses and long-term tumour clearance; reovirus-loaded DC, in contrast, generated only an anti-viral immune response. In reovirus-immune mice, however, the results were different. Neat reovirus was completely ineffective as a therapy, whereas mDC--though not iDC--as well as T cells, effectively delivered reovirus to melanoma in vivo for therapy and anti-tumour immune priming. Moreover, mDC were more effective than T cells over a range of viral loads. These data show that systemically administered neat reovirus is not optimal for therapy, and that DC may be an appropriate vehicle for carriage of significant levels of reovirus to tumours. The pre-existing immune status against the virus is critical in determining the balance between anti-viral and anti-tumour immunity elicited when reovirus is delivered by cell carriage, and the viral dose and mode of delivery, as well as the immune status of patients, may profoundly affect the success of any clinical anti-tumour viral therapy. These findings are therefore of direct translational relevance for the future design of clinical trials.}, } @article {pmid19280264, year = {2009}, author = {Boughey, JC and Wagner, J and Garrett, BJ and Harker, L and Middleton, LP and Babiera, GV and Meric-Bernstam, F and Lucci, A and Hunt, KK and Bedrosian, I}, title = {Neoadjuvant chemotherapy in invasive lobular carcinoma may not improve rates of breast conservation.}, journal = {Annals of surgical oncology}, volume = {16}, number = {6}, pages = {1606-1611}, pmid = {19280264}, issn = {1534-4681}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/*drug therapy/surgery ; Carcinoma, Lobular/*drug therapy/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mastectomy/statistics & numerical data ; Mastectomy, Segmental/*statistics & numerical data ; Middle Aged ; Neoadjuvant Therapy ; Retrospective Studies ; }, abstract = {BACKGROUND: Patients with invasive lobular carcinoma (ILC) experience a lower pathological complete response rate to neoadjuvant chemotherapy than patients with invasive ductal carcinoma. This study was intended to evaluate the impact of neoadjuvant chemotherapy in ILC on breast-conserving surgery (BCS) rates.

METHODS: Two-hundred eighty-four consecutive patients with pure ILC treated between May 1998 and September 2006 were reviewed. Surgical procedures and long-term outcomes were compared between patients receiving neoadjuvant chemotherapy and those receiving surgery first.

RESULTS: Neoadjuvant chemotherapy was administered to 84 patients; 200 patients underwent surgery first. The mean tumor size in the neoadjuvant group (4.9 cm) was significantly larger than in patients who underwent surgery first (2.5 cm, p < 0.0001). In the neoadjuvant group, clinical complete response was seen in 10% and partial response in 59%. Overall BCS rates were 17% in the neoadjuvant group compared with 43% in the surgery-first group (p < 0.0001). When controlled for initial tumor size, there was no difference (all p > 0.05) between the groups in terms of (1) the proportion of patients who underwent an initial attempt at BCS, (2) rate of failure of BCS or (3) the proportion of patients undergoing BCS as their final procedure. With a mean follow-up of 47 months, local recurrence (LR) rates were similar between the two groups (1.2% versus 0.5%, p = 0.5).

CONCLUSION: The use of neoadjuvant chemotherapy does not increase the rates of breast conservation in patients with pure ILC.}, } @article {pmid19274027, year = {2009}, author = {Leone, A and Laudani, R and Definite, G and Martini, R and Andreozzi, GM}, title = {Unbalanced risk factors, could compromise the effectiveness of physical training in patients with intermittent claudication?.}, journal = {Minerva cardioangiologica}, volume = {57}, number = {2}, pages = {165-174}, pmid = {19274027}, issn = {0026-4725}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Analysis of Variance ; Cohort Studies ; Exercise Therapy/*methods ; Exercise Tolerance ; Female ; Humans ; Intermittent Claudication/diagnosis/physiopathology/*rehabilitation ; Male ; Middle Aged ; Multivariate Analysis ; Program Evaluation ; Recovery of Function ; Resistance Training ; Risk Factors ; Secondary Prevention ; Severity of Illness Index ; Smoking/adverse effects ; Treatment Outcome ; Walking ; }, abstract = {AIM: The correction of atherosclerotic risk factors is the unavoidable assumption to assure the maximal effectiveness and duration of the results of any therapeutic intervention (pharmacological and surgical) for the treatment of intermittent claudication. Aim of this study has been to verify if the presence/absence of risk factors and the degree of their correction could compromise the responsiveness of claudicant patients to the supervised physical training.

METHODS: Initial (IDC), absolute (ACD) claudication distance, and recovery time (RT) have been measured by maximal treadmill exercise in 74 claudicants. The measurements have been repeated after 18 days of supervised physical training consisting of a daily walk reaching either a distance goal of 1-2 km or a time goal of at least 30 min. The working load of each single training session has been tailored at 60-70% of the ACD measured by a non-maximal treadmill exercise. The patients' cohort has been stratified in 7 groups and 18 sub-groups (no smokers, smokers in the past, still smokers, no-diabetics, well balanced and unbalanced diabetes, absent, well balanced and unbalanced hypercholesterolemia, normal weight, over weight and light obesity, hypertensive and no-hypertensive, with and without previous myocardial infarction and TIAs or stroke). The mean and standard error of ICD, ACD and RT before and after 18 days of physical training have been calculated and compared with Student's t test in each group and sub-group. On the data before and after training of ICD, ACD and RT of each group of risk factors the multivariate analysis of the variance has been carried out by analysis of variance (ANOVA). All the analyses were considered significant when the P value was less than 0.05.

RESULTS: ICD values increased from 55.12 to 121.86 m, ACD from 103.16 to 191.58 m, RT reduced from 204.04 to 87.46 s, confirming the relevant (P<0.0001) effectiveness of supervised physical training on the walking capacity of claudicant patients. The comparison between the deltas (value after minus value before) of each sub-group did not show any significant difference. The multivariate ANOVA of before and after ICD ACD and RT of each risk factor groups showed values relevantly lesser than 0.05, indicating that risk factors did not influence the result of physical training.

CONCLUSIONS: The supervised physical training is confirmed as an effective tool for the treatment of claudicant patient. We did not find any significant difference in the response to the programme related with the presence, absence or balance degree of risk factors, and we conclude that physical training effectiveness is independent from the their presence, absence or balance degree. This statement is very important because highlights the physical training as the only therapeutic tool for peripheral arterial disease (PAD) independent from the results of the risk factors' treatment.}, } @article {pmid19267929, year = {2009}, author = {Seniski, GG and Camargo, AA and Ierardi, DF and Ramos, EA and Grochoski, M and Ribeiro, ES and Cavalli, IJ and Pedrosa, FO and de Souza, EM and Zanata, SM and Costa, FF and Klassen, G}, title = {ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma.}, journal = {BMC cancer}, volume = {9}, number = {}, pages = {80}, pmid = {19267929}, issn = {1471-2407}, mesh = {ADAM Proteins/*genetics ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Lobular/*genetics/pathology ; Cell Line, Tumor ; DNA Methylation ; Female ; Gene Expression/genetics ; *Gene Silencing ; Humans ; Middle Aged ; Promoter Regions, Genetic/genetics ; }, abstract = {BACKGROUND: ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer.

METHODS: First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test.

RESULTS: The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was statistically significant (p = 0.0002).

CONCLUSION: ADAM33 gene silencing may be related to the discohesive histological appearance of ILCs. We suggest that ADAM33 promoter methylation may be a useful molecular marker for differentiating ILC and IDC.}, } @article {pmid19267401, year = {2009}, author = {Chen, C and Zhou, Z and Sheehan, CE and Slodkowska, E and Sheehan, CB and Boguniewicz, A and Ross, JS}, title = {Overexpression of WWP1 is associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma.}, journal = {International journal of cancer}, volume = {124}, number = {12}, pages = {2829-2836}, doi = {10.1002/ijc.24266}, pmid = {19267401}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/pharmacology ; Biomarkers, Tumor/metabolism ; Blotting, Western ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Carcinoma, Lobular/drug therapy/*metabolism/secondary ; Cell Proliferation/drug effects ; Estrogen Receptor alpha/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Small Interfering/pharmacology ; Receptor, IGF Type 1/*metabolism ; Tamoxifen/pharmacology ; Tumor Cells, Cultured ; Ubiquitin-Protein Ligases/antagonists & inhibitors/genetics/*metabolism ; Up-Regulation ; }, abstract = {WWP1, a HECT type E3 ubiquitin ligase frequently amplified and overexpressed in breast cancer, has the potential to become a useful clinical biomarker and therapeutic target in breast cancer. Here, we performed immunohistochemical staining in formalin-fixed and paraffin-embedded tissue sections from 187 cases of primary invasive mammary carcinoma [137 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC)] by using a monoclonal anti-WWP1 antibody. The normal breast epithelium and adjacent benign epithelium are essentially negative for WWP1. Cytoplasmic WWP1 immunoreactivity was observed in 76/187 (40.6%) tumors and showed a positive correlation with ERalpha (p = 0.05) and IGF-1R proteins (p = 0.001) in this cohort. The positive correlations between WWP1 and ER/IGF-1R were also observed in a panel of 12 breast cancer cell lines by Western blot. Interestingly, the ER levels are decreased when WWP1 is silenced in ER positive MCF7 and T47D breast cancer cell lines. Finally, WWP1 ablation collectively inhibits cell proliferation with tamoxifen in MCF7 and T47D, as measured by (3)H-thymidine incorporation assays. These findings suggest that WWP1 may play an important role in ER positive breast cancer.}, } @article {pmid19266279, year = {2010}, author = {Chen, DT and Nasir, A and Culhane, A and Venkataramu, C and Fulp, W and Rubio, R and Wang, T and Agrawal, D and McCarthy, SM and Gruidl, M and Bloom, G and Anderson, T and White, J and Quackenbush, J and Yeatman, T}, title = {Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.}, journal = {Breast cancer research and treatment}, volume = {119}, number = {2}, pages = {335-346}, pmid = {19266279}, issn = {1573-7217}, support = {R01 CA112215/CA/NCI NIH HHS/United States ; R01 CA098522-05/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; R01CA112215/CA/NCI NIH HHS/United States ; R01 CA 098522/CA/NCI NIH HHS/United States ; R01 CA112215-03/CA/NCI NIH HHS/United States ; R01 CA098522/CA/NCI NIH HHS/United States ; P30 CA076292-07/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology/surgery ; Case-Control Studies ; *Cell Proliferation ; Female ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Predisposition to Disease ; *Genetic Testing ; Humans ; Mastectomy ; *Oligonucleotide Array Sequence Analysis ; Precancerous Conditions/chemistry/*genetics/pathology ; Principal Component Analysis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Risk Factors ; }, abstract = {Historical data have indicated the potential for the histologically-normal breast to harbor pre-malignant changes at the molecular level. We postulated that a histologically-normal tissue with "tumor-like" gene expression pattern might harbor substantial risk for future cancer development. Genes associated with these high-risk tissues were considered to be "malignancy-risk genes". From a total of 90 breast cancer patients, we collected a set of 143 histologically-normal breast tissues derived from patients harboring breast cancer who underwent curative mastectomy, as well as a set of 42 invasive ductal carcinomas (IDC) of various histologic grades. All samples were assessed for global gene expression differences using microarray analysis. For the purpose of this study we defined normal breast tissue to include histologically normal and benign lesions. Here we report the discovery of a "malignancy-risk" gene signature that may portend risk of breast cancer development in benign, but molecularly-abnormal, breast tissue. Pathway analysis showed that the malignancy-risk signature had a dramatic enrichment for genes with proliferative function, but appears to be independent of ER, PR, and HER2 status. The signature was validated by RT-PCR, with a high correlation (Pearson correlation = 0.95 with P < 0.0001) with microarray data. These results suggest a predictive role for the malignancy-risk signature in normal breast tissue. Proliferative biology dominates the earliest stages of tumor development.}, } @article {pmid19256762, year = {2008}, author = {Nurismah, MI and Noriah, O and Suryati, MY and Sharifah, NA}, title = {E-cadherin expression correlates with histologic type but not tumour grade in invasive breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {9}, number = {4}, pages = {699-702}, pmid = {19256762}, issn = {2476-762X}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast Neoplasms/*chemistry/*pathology ; Cadherins/*analysis ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; Carcinoma, Lobular/*chemistry/*pathology ; Chi-Square Distribution ; Cohort Studies ; Diagnosis, Differential ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness/genetics/*pathology ; Neoplasm Staging ; Probability ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {The traditional classification of infiltrating breast carcinomas into ductal and lobular can be diagnostically challenging in a small proportion of cases with equivocal histological features and in in-situ lesions with overlapping features. Distinguishing between the infiltrating ductal (IDC) and lobular (ILC) carcinomas is clinically important because of the different pattern of systemic metastases and prognostic evaluation. E-cadherin is a potentially useful immunohistochemical marker which may serve to differentiate between the two tumour types. We therefore studied E-cadherin expression in 32 cases of breast carcinomas comprising 16 IDCs and 16 ILCs. The correlation between E-cadherin expression and the histological grade of IDCs was also analysed. Our results showed complete loss of E-cadherin expression in all ILCs, while the IDCs consistently showed variable E-cadherin positivity. No significant correlation was found between E- cadherin expression and the histological grade of IDCs. We conclude from this study that E-cadherin is a useful marker to differentiate between IDC and ILC of the breast. A larger study of IDCs is now needed to further evaluate the correlation between E-cadherin and tumour grade to estimate its prognostic potential.}, } @article {pmid19250851, year = {2009}, author = {Yoney, A and Kucuk, A and Unsal, M}, title = {Male breast cancer: a retrospective analysis.}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {13}, number = {2}, pages = {103-107}, doi = {10.1016/j.canrad.2008.11.011}, pmid = {19250851}, issn = {1278-3218}, mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms, Male/*mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Carcinoma, Lobular/mortality/pathology/therapy ; Carcinoma, Papillary/mortality/pathology/therapy ; Disease-Free Survival ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Retrospective Studies ; }, abstract = {BACKGROUND: To evaluate our results in the treatment of male breast cancer patients with respect to local control (LC), overall survival (OS) and possible prognosis factors for survival.

PATIENTS AND METHODS: Thirty-nine patients with male breast cancer have been retrospectively studied with the trial aim to evaluate the results of our practice. Among them, 94.8% had invasive ductal carcinoma (IDC), 2.6% invasive papillary carcinoma (IPC) and 2.6% invasive lobular carcinoma (ILC) and the distribution according to stage was found to be 12.8, 46.2, 30.7 and 10.3% in Stages I, II, III and IV, respectively. Among the patients, 7.7% received radiotherapy (RT) and hormonotherapy (HT), 22.8% received chemotherapy (CT), 61.8% received chemoradiotherapy (CRT) and HT and 7.7% received HT in addition to surgery.

RESULTS: The distant metastases rate was 36% and the local recurrence rate was 5%. All the local recurrences and the distant metastases had occurred after the first two years. The five-year disease free survival (DFS) and OS rates were 65.8 and 80.1% respectively. In our series, univariate analysis for OS demonstrated statistical significance for lymph node metastases (p=0.00001), stage (p=0.0098) and age (p=0.03); while RT in the treatment modality (p=0.6849), and tumor size (p=0.4439) demonstrated no significance. The presence of lymph node metastases significantly impairs OS (p=0.004) and DFS (p=0.014) in multivariate analysis.

CONCLUSION: Postoperative radiotherapy was important in the management of male breast cancer to improve LC resulting in one local failure, but did not improve OS and DFS in our analysis. The presence of lymph node metastases significantly impaired OS and DFS.}, } @article {pmid19242778, year = {2009}, author = {Rokutanda, N and Horiguchi, J and Koibuchi, Y and Nagaoka, R and Sato, A and Odawara, H and Tokiniwa, H and Iino, Y and Hirato, J and Takeyoshi, I}, title = {Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement: a case report with a false-negative sentinel lymph node biopsy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {162-165}, doi = {10.1007/s12282-008-0089-1}, pmid = {19242778}, issn = {1880-4233}, mesh = {Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; False Negative Reactions ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Staging ; Sentinel Lymph Node Biopsy ; }, abstract = {A 54-year-old woman visited our hospital with a palpable tumor in her left breast, which was diagnosed as invasive ductal carcinoma. Breast-conserving surgery was performed, in association with a sentinel lymph node (SLN) biopsy and back-up dissection of the axillary lymph nodes. One dyed axillary lymph node with high radioactivity was defined as an SLN, and intraoperative frozen-section analysis of the SLN was negative for metastasis. The final pathological diagnosis of the tumor was invasive ductal carcinoma, and one small lymph node, located in the retromammary space, just under the tumor, was positive for metastasis. The backup axillary lymph nodes were not metastatic. This patient was diagnosed false-negative by SLN biopsy, despite being positive for retroMLN metastasis. It should be recognized that retroMLNs are difficult to detect preoperatively, or intra-operatively, using dye or radiocolloid, if they are located in the post-tumoral retro-mammary space. RetroMLNs may be a pitfall in SLN biopsies.}, } @article {pmid19242056, year = {2009}, author = {Mohammadizadeh, F and Ghasemibasir, H and Rajabi, P and Naimi, A and Eftekhari, A and Mesbah, A}, title = {Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {5}, number = {1}, pages = {1-8}, doi = {10.3233/CBM-2009-0551}, pmid = {19242056}, issn = {1574-0153}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Female ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/metabolism ; Middle Aged ; Paraffin Embedding ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression in breast cancer. The aim of this study is the assessment of relationship between E-cadherin expression and routine prognostic biomarkers as well as grading and lymph node status in breast invasive ductal carcinomas. . The associations between co-expression of E-cadherin and other biomarkers on one hand and grading, proliferating index and lymph node status on the other have also been evaluated.

OBJECTIVE: To evaluate the correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma.

METHODS: 108 formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma "NOS" type) from the pathology archive of Alzahra hospital(Isfahan, Iran) which had been studied for expression of routine molecular biomarkers were selected. E-cadherin expression was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing E-cadherin staining.

RESULTS: No association was found between E-cadherin alteration and ER, PR, p53, Ki67 and HER2/neu status of breast cancer. However, E-cadherin alteration showed a significant difference between grading and also lymph node groups. There was no association between co-expression of E-cadherin/ER, E-cadherin/PR, E-cadherin/Her-2neu, E-cadherin/p53 and Her-2neu/p53 on one hand and Ki67 status and tumor grade on the other. Co-expressions of E-cadherin/Her-2neu and E-cadherin/p53 showed significant difference in lymph node groups.

CONCLUSION: We found that E-cadherin alteration in breast cancer has an association with other important prognostic factors. Evaluation of E-cadherin status can help, independently or in addition to conventional biological prognostic markers, to identify prognosis of breast cancer.}, } @article {pmid19239320, year = {2009}, author = {Cholujova, D and Jakubikova, J and Sedlak, J}, title = {BioBran-augmented maturation of human monocyte-derived dendritic cells.}, journal = {Neoplasma}, volume = {56}, number = {2}, pages = {89-95}, doi = {10.4149/neo_2009_02_89}, pmid = {19239320}, issn = {0028-2685}, mesh = {B7-1 Antigen/analysis ; B7-2 Antigen/analysis ; Cell Differentiation/drug effects ; Dendritic Cells/*drug effects/immunology/physiology ; Endocytosis/drug effects ; Humans ; Interleukin-3 Receptor alpha Subunit/analysis ; Monocytes/*cytology ; Receptors, Interleukin-3/analysis ; Xylans/*pharmacology ; }, abstract = {UNLABELLED: BioBran, enzymatically modified arabinoxylan from rice bran was tested for its possible effects on in vitro maturation of human dendritic cells (DC). Immature DC (iDC) derived from plastic-adhered, IL-4 and GM-CSF treated peripheral monocytes (Mo) were further cultured with cytokine maturation mix 1 (CMM1; TNF-alpha, IL-1beta and IL-6) or CMM2 (LPS and IFN-gamma) to induce their maturation into mature DC (matDC1 or matDC2, respectively). Different concentrations of BioBran (10, 100, 400 and 1000 microg/ml) were applied in the presence or absence of relevant CMM to assess the effects of BioBran on DC maturation processes. BioBran induced maturation of iDC, as these cells cultured with IL-4/GM-CSF/BioBran down-regulated CD14 and CD1a antigens on cell surface and significantly increased expression of maturation marker CD83. The increase of surface density of costimulatory molecules CD80 and CD86 on iDC in the presence of BioBran was also observed. In addition, BioBran induced functional maturation of iDC, confirmed by decreased endocytic activity of iDC. Further emore, BioBran enhanced maturation potential of cytokine mixes, as both matDC1 and matDC2 exposed to BioBran completely lost CD14 and upregulated CD83, CD80 and CD86 antigens, in comparison to DC matured with the relevant CMM alone. BioBran also increased CD123 antigen expression on all DC subsets. Interestingly, matDC2 matured in the presence of BioBran (400microg/ml) expressed higher levels of CD123 and lower levels of CD11c cell surface antigens, the phenotype represented by CD11c[dim] CD123[bright] plasmacytoid DC population. These data demonstrate that BioBran is a potent enhancer of DC maturation and suggest that BioBran might be a useful agent to create the environment that favours DC maturation.

KEYWORDS: Dendritic cell, maturation, BioBran, buffy coat.}, } @article {pmid19225570, year = {2009}, author = {Keriel, A and Mahuteau-Betzer, F and Jacquet, C and Plays, M and Grierson, D and Sitbon, M and Tazi, J}, title = {Protection against retrovirus pathogenesis by SR protein inhibitors.}, journal = {PloS one}, volume = {4}, number = {2}, pages = {e4533}, pmid = {19225570}, issn = {1932-6203}, mesh = {Animals ; Animals, Newborn ; Indoles/*pharmacology ; Leukemia Virus, Murine/genetics/*pathogenicity ; Leukemia, Erythroblastic, Acute/drug therapy/*prevention & control ; Mice ; Nuclear Proteins/*antagonists & inhibitors ; RNA Splicing ; RNA-Binding Proteins ; Retroviridae ; Serine-Arginine Splicing Factors ; }, abstract = {Indole derivatives compounds (IDC) are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE)-dependent activity of individual serine-arginine-rich (SR) proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV) develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents.}, } @article {pmid19224162, year = {2009}, author = {Liu, C and Pan, H and Li, Z and Shi, L and Huang, T}, title = {Histopathological features of invasion of breast invasive ductal carcinoma and safety of breast-conserving surgery.}, journal = {Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban}, volume = {29}, number = {1}, pages = {50-52}, pmid = {19224162}, issn = {1672-0733}, mesh = {Adolescent ; Adult ; Aged ; Axilla ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/metabolism/*pathology/surgery ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/genetics/*metabolism ; Young Adult ; }, abstract = {In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery, the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed. The correlation analysis on invasive extent, which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre, and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading was processed. There was a significant correlation between invasive extent and tumor size (r=0.766, P<0.01), and lymph nodes metastases (r=0.574, P<0.01), but there was no significant correlation between invasive extent and Her-2 expression (r=0.106, P>0.05), and histologic grading (r=0.228, P>0.05). The 100% negative rate of infiltration in patients without nipple discharge with tumor size <2, 2-3 and >3 cm was obtained at 1.5, 2.0 and 2.5 cm away from the tumor respectively. It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.}, } @article {pmid19215229, year = {2009}, author = {Niu, Y and Liu, T and Tse, GM and Sun, B and Niu, R and Li, HM and Wang, H and Yang, Y and Ye, X and Wang, Y and Yu, Q and Zhang, F}, title = {Increased expression of centrosomal alpha, gamma-tubulin in atypical ductal hyperplasia and carcinoma of the breast.}, journal = {Cancer science}, volume = {100}, number = {4}, pages = {580-587}, doi = {10.1111/j.1349-7006.2008.01075.x}, pmid = {19215229}, issn = {1349-7006}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Centrosome/metabolism ; Female ; Humans ; Immunohistochemistry ; Precancerous Conditions/genetics/metabolism/*pathology ; Tubulin/genetics/*metabolism ; }, abstract = {Centrosomal abnormalities have been found in various cancer types. We sought to determine whether centrosomal dysfunctions occur in the atypical ductal hyperplasia (ADH)-carcinoma sequence of breast cancer. As alpha and gamma-tubulins are the structural components of centrosomes, we performed real time quantitative polymerase chain reaction (qPCR), in situ hybridization (ISH) and immunnohistochemistry (IHC) to determine the DNA copy levels, messenger RNA (mRNA) expression, and protein expression of alpha and gamma-tubulins respectively. Gamma-tubulin staining was used for the localization and quantification of centrosomes. We found that alpha-tubulin or gamma-tubulin mRNA was increasingly expressed from normal breast tissue (NBT) to ADH, ductal carcinoma in situ (DCIS), and infiltrative ductal carcinoma (IDC), respectively, with the highest expressions being found in DCIS. The expression profiles of alpha, gamma-tubulin proteins were concordant with that of mRNA, except that the highest expression was found in IDC. Similarly, DNA copies of alpha, gamma-tubulins showed a rising tendency, with the highest level for gamma-tubulin attained in IDC and that for alpha-tubulin was found in DCIS. However, there was no significant difference of alpha, gamma-tubulin DNA copy levels, mRNA expression, and protein expression between DCIS and IDC. Our results demonstrate that centrosomal aberrations may play key roles in the early stage of breast tumorogenesis. The malignant transformation sequence is probably attributable to the amplification of centrosomal DNA leading to mRNA and protein over-expression of these centrosomal proteins. Furthermore, determination of alpha, gamma-tubulins using combined qPCR with ISH may be useful in assisting the diagnosis of premalignant lesions of the breast.}, } @article {pmid19214938, year = {2009}, author = {Tourny-Chollet, C and Seifert, L and Chollet, D}, title = {Effect of force symmetry on coordination in crawl.}, journal = {International journal of sports medicine}, volume = {30}, number = {3}, pages = {182-187}, doi = {10.1055/s-0028-1104581}, pmid = {19214938}, issn = {1439-3964}, mesh = {Adolescent ; Functional Laterality ; Humans ; Male ; Motor Skills/*physiology ; *Respiration ; Rotator Cuff/physiology ; Shoulder Joint/physiology ; *Swimming ; Young Adult ; }, abstract = {The relationship between breathing laterality and motor coordination symmetry as a function of the symmetry of medial rotator muscle force in the shoulders was investigated. The principal objective was to distinguish swimmer profiles. Thirteen expert male swimmers performed the front crawl and were assessed for: (i) inter-arm coordination with the IdC and arm coordination symmetry with the Symmetry Index, (ii) breathing laterality, and (iii) the symmetry of the isokinetic force in the shoulder medial rotators. The results indicated that the relative duration of catch+pull was greater for the dominant arm (51.7%) than for the non-dominant arm (48.4%) for the swimmers with force asymmetry (p<0.05) and occurred on the side with the higher force (dominant arm). Two profiles were revealed: (i) swimmers for whom breathing laterality was related to force symmetry and stroke phase duration and (ii) swimmers for whom the impact of breathing laterality on force symmetry and stroke duration was low. The first profile corresponded to sprint specialists and the second profile corresponded more to middle-distance specialists.}, } @article {pmid19214111, year = {2009}, author = {Shah, SS and Wang, Y and Tull, J and Zhang, S}, title = {Effect of high copy number of HER2 associated with polysomy 17 on HER2 protein expression in invasive breast carcinoma.}, journal = {Diagnostic molecular pathology : the American journal of surgical pathology, part B}, volume = {18}, number = {1}, pages = {30-33}, doi = {10.1097/PDM.0b013e31817c1af8}, pmid = {19214111}, issn = {1533-4066}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; *Chromosomes, Human, Pair 17 ; Female ; *Gene Dosage ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Middle Aged ; Polyploidy ; Receptor, ErbB-2/*biosynthesis ; }, abstract = {HER2 gene amplification by fluorescence in situ hybridization and protein expression by immunohistochemistry (IHC) have been used for prognosis and guiding treatment of invasive ductal carcinoma of the breast with trastuzumab. Accurate evaluation of HER2 status is important in the management of patients with candidacy for the HER2-targeting therapy. Despite previous studies, effects of polysomy of chromosome 17, at which HER2 is located, on HER2 protein expression remains controversial. In this study, we calculated the average copy numbers of HER2 and chromosome 17 (CEP17) per nucleus in 109 cases of invasive breast carcinoma and analyzed their correlations with the HER2/CEP17 ratio and protein expression. As expected, there were close correlations between HER2 protein expression and the HER2/CEP17 ratio (CC: 0.49, P<0.001), along with the HER2 copy number per nucleus (CC: 0.48, P<0.001) and between the CEP17 copy number per nucleus and the HER2 copy number per nucleus (CC: 0.45, P<0.001). Correlation between the CEP17 copy number per nucleus and the HER2/CEP17 ratio was not significant (CC: 0.2, P>0.05). There was a weak, but statistically insignificant, correlation between the CEP17 copy number per nucleus and HER2 protein expression by IHC (CC: 0.26, P>0.05). The cases were then grouped on the basis of the amplification of the HER2 gene by fluorescence in situ hybridization. In the cases that showed no amplification, there was a significantly higher CEP17 copy number per nucleus in cases with strong HER2 protein expression (2.99) when compared with cases with weak (2.39) or absent (1.86) expression. In conclusion, a high HER2 gene copy number-associated polysomy 17 is a significant contributing factor in HER2 protein overexpression in unamplified invasive breast carcinomas. Cases without HER2 amplification, but carrying polysomy 17, should be further evaluated for HER2 protein overexpression by IHC. Those with polysomy 17-associated HER2 protein overexpression, like any other IHC+ ones, should be eligible candidates for trastuzumab therapy.}, } @article {pmid19212625, year = {2009}, author = {Huang, GL and Zhang, XH and Guo, GL and Huang, KT and Yang, KY and Shen, X and You, J and Hu, XQ}, title = {Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {21}, number = {3}, pages = {673-679}, pmid = {19212625}, issn = {1021-335X}, mesh = {Benzothiazoles ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Diamines ; Female ; Humans ; Immunohistochemistry ; MicroRNAs/*biosynthesis ; Neoplasm Staging ; Organic Chemicals ; PTEN Phosphohydrolase/*biosynthesis ; Quinolines ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Growing evidence suggests microRNAs (miRNAs) have an important role in tumorigenesis. MicroRNA-21 (miR-21) is up-regulated in many malignant tumors, including breast cancer. Its association with clinicopathologic features and expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10), one of its target genes, in breast cancer has not been reported systematically. To further determine the potential involvement of miR-21 in breast cancer, we have evaluated the expression level of miR-21 by stem-loop real-time RT-PCR based on SYBR-Green I in human invasive ductal carcinoma of the breast, and we have correlated the results with clinicopathologic features and PTEN protein expression. Matched non-tumor and tumor tissues of 40 human invasive ductal carcinoma of the breast were analyzed for miR-21 expression by stem-loop real-time RT-PCR based on SYBR-Green I. Immunohistochemistry (IHC) was used to estimate PTEN expression in tumor tissue. The expression levels of miR-21 were correlated with PTEN and commonly used clinicopathologic features of breast cancer. The stem-loop real-time RT-PCR based on SYBR-Green I was sensitive and specific enough to detect miR-21. Expression levels of miR-21 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P=0.000). Expression of miR-21 was negatively correlated with expression of PTEN (P=0.013). Up-regulated miR-21 expression was associated with lymph node positivity (P=0.01), higher proliferation index (ki67>10%) (P=0.03) and advanced breast cancer TNM clinical stage (P=0.021). These findings suggest that PTEN is possibly one of the targets of miR-21 in breast cancer and high expression of mir-21 indicates a more aggressive phenotype.}, } @article {pmid19208524, year = {2009}, author = {Sanada, Y and Yoshida, K and Itoh, M and Okita, R and Okada, M}, title = {Invasive ductal carcinoma of the pancreas showing exophytic growth.}, journal = {Hepatobiliary & pancreatic diseases international : HBPD INT}, volume = {8}, number = {1}, pages = {97-102}, pmid = {19208524}, issn = {1499-3872}, mesh = {Adenocarcinoma, Mucinous/diagnostic imaging/*pathology/surgery ; Aged ; Carcinoembryonic Antigen/blood ; Carcinoma, Pancreatic Ductal/diagnostic imaging/*pathology/surgery ; Cholangiopancreatography, Magnetic Resonance ; Female ; Giant Cells/pathology ; Humans ; Mucin-1/metabolism ; Pancreatic Ducts/diagnostic imaging/*pathology ; Pancreatic Neoplasms/diagnostic imaging/*pathology/surgery ; Phagocytosis ; Positron-Emission Tomography ; }, abstract = {BACKGROUND: Invasive pancreatic carcinoma generally appears as poorly defined mass reflecting the infiltrative growth. We aimed to identify the histological and immunohistochemical features in a rare case of pancreatic carcinoma showing exophytic growth.

METHODS: A 67-year-old woman presented with a mass of 5.0 cm in diameter in the pancreatic head. Preoperative computed tomography revealed a well-demarcated, primarily solid mass with a central low-density area. Magnetic resonance cholangiopancreatography revealed neither encasement nor dilation of the main pancreatic duct. An incorrect preoperative diagnosis was made of solid pseudopapillary tumor of the pancreas. Elevated serum carcinoembryonic antigen (CEA) levels and abnormal FDG positron emmission tomography accumulation suggested that the tumor had malignant potential requiring a pancreatoduodenectomy.

RESULTS: The head of the pancreas contained a well-circumscribed encapsulated mass of 5.0 cm in diameter, comprising 50% adenocarcinoma, with mucinous carcinoma in the center and anaplastic carcinoma at the periphery. The anaplastic carcinoma comprised pleomorphic cells (PCs) and pleomorphic giant cells (PGCs). The PGCs phagocytozed mononuclear PCs and lymphocytes adjacent to the capsule without infiltrating the capsule itself. Immunohistochemistry revealed that the anaplastic carcinoma cells including PGCs were positive for the tumor antigen Mucin 1 and CEA but negative for vimentin.

CONCLUSION: Our observations suggest anaplastic carcinoma components in the present tumor have a ductal origin and that the exophytic tumor growth is associated with the phagocytotic activity of PGCs.}, } @article {pmid19207951, year = {2009}, author = {Faratian, D and Munro, A and Twelves, C and Bartlett, JM}, title = {Membranous and cytoplasmic staining of Ki67 is associated with HER2 and ER status in invasive breast carcinoma.}, journal = {Histopathology}, volume = {54}, number = {2}, pages = {254-257}, doi = {10.1111/j.1365-2559.2008.03191.x}, pmid = {19207951}, issn = {1365-2559}, mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/*metabolism ; Prognosis ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/*metabolism ; }, abstract = {AIMS: Membranous and cytoplasmic Ki67 immunoreactivity has recently been observed in a number of histopathological entities, but frequency of occurrence and relationship to prognosis in more common cancers have not been described. The aim was to describe the pattern and frequency of membranous/cytoplasmic Ki67 in a cohort of invasive breast carcinomas, and their associations with grade, HER2 amplification and oestrogen receptor (ER) expression.

METHODS AND RESULTS: Three hundred and twenty-two cases of invasive ductal carcinoma were assessed for histological grade, Ki67 (MIB-1 clone) proliferation index and pattern of immunoreactivity, ER expression by immunohistochemistry, and HER2 amplification status by fluorescence in situ hybridization. Overall, 26/322 (8%) breast carcinomas showed membranous/cytoplasmic Ki67, and expression was significantly associated with grade 3, HER2-amplified and ER- tumours. Membranous/cytoplasmic Ki67 was not, however, an independent prognostic factor on multivariate analysis.

CONCLUSIONS: Membranous/cytoplasmic Ki67 identifies a group of breast carcinomas that may be important to consider separately in prognostic and predictive studies. The mechanism of subcellular Ki67 relocalization remains elusive and further studies are required to establish both the cause and effect of this unusual pattern of Ki67 immunoreactivity.}, } @article {pmid19205832, year = {2009}, author = {Yamashiro, N and Tozaki, M and Ogawa, T and Kawano, N and Suzuki, T and Ozaki, S and Sakamoto, N and Abe, S and Fukuma, E}, title = {Preoperative MRI marking technique for the planning of breast-conserving surgery.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {3}, pages = {223-228}, doi = {10.1007/s12282-008-0088-2}, pmid = {19205832}, issn = {1880-4233}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mastectomy, Segmental/*methods ; Middle Aged ; Preoperative Care ; Retrospective Studies ; Supine Position ; Ultrasonography, Mammary ; }, abstract = {BACKGROUND: When performing breast-conserving surgery (BCS), it is essential to achieve a complete resection of the tumor while preserving the cosmetic outcome. The aim of this study was to evaluate the accuracy of a MRI marking technique for planning of BCS.

METHODS: A retrospective review was performed of 14 consecutive patients who underwent MRI in the supine position (supine MRI) using a MRI marking technique. The preoperative histopathological diagnosis was ductal carcinoma in situ in 11 and invasive ductal carcinoma in 3. All of the patients with invasive ductal carcinoma were treated with neoadjuvant chemotherapy. The pills of Breath Care used as MRI markers were placed in the Penrose drain with 2-cm intervals, and drains were put on the resection lines as determined by ultrasonography (US). The final resection lines were modified using information obtained by supine MRI. The rate of the margin-tumor distance (RMTD: longer margin-tumor distance/shorter margin-tumor distance) was calculated.

RESULTS: Thirteen patients (93%) needed modification of the first resection line, whereas one patient (7%) needed no modification. Twelve patients (86%) had negative margins, but two patients (14%) had positive margins: one patient had a medial margin, while the other had a distal margin. One patient showed a pathologically complete response after chemotherapy; the RMTD was not evaluated. Among the 12 patients with medial and lateral negative margins, the medial and lateral margin-tumor distances ranged from 1.0 to 3.5 cm (average 2.1 cm), and the RMTD ranged from 1 to 3.0 (average 1.5).

CONCLUSION: Our MRI marking technique may be useful for evaluating the extent of the tumor as determined by the US examination in difficult cases.}, } @article {pmid19205420, year = {2008}, author = {Sarcević, B}, title = {[Histopathologic diagnosis of luminal and basal type breast cancer].}, journal = {Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti}, volume = {62}, number = {4}, pages = {427-430}, pmid = {19205420}, issn = {1330-0164}, mesh = {Breast Neoplasms/diagnosis/genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/*pathology ; Female ; Gene Expression Profiling ; Humans ; Oligonucleotide Array Sequence Analysis ; Prognosis ; }, abstract = {Despite tremendous advances in breast cancer characterization and therapy over the last 20 years, clinicians still have difficulty to accurately predict the prognosis in individual breast cancer patients. Patients with identical histologic tumor characteristics can have markedly different outcome in terms of distant metastasis-free and overall survival. The most common breast cancer is invasive ductal carcinoma, which is heterogeneous and according to immunohistochemical markers is divided in the luminal and basal type, as also identified by the recent expression profiling method. Microarray expression profiling is a novel method to further characterize breast cancer tumors at the gene expression level. Breast cancer subtypes have been described which display different biological behaviors. In addition, groups of genes known as gene-signatures have been identified, which provide more accurate prognostic factors than current clinical and histologic features. Future clinical decisions may rely on expression profiling of breast tumors.}, } @article {pmid19204586, year = {2009}, author = {Alberty, M and Sidney, M and Pelayo, P and Toussaint, HM}, title = {Stroking characteristics during time to exhaustion tests.}, journal = {Medicine and science in sports and exercise}, volume = {41}, number = {3}, pages = {637-644}, doi = {10.1249/MSS.0b013e31818acfba}, pmid = {19204586}, issn = {1530-0315}, mesh = {Adult ; Fatigue/physiopathology ; Female ; Humans ; Male ; Models, Biological ; Physical Endurance/*physiology ; Swimming/*physiology ; }, abstract = {PURPOSE: Race analyses during swimming reveal how exercise duration affects both clean swimming speed (v), stroke rate (SR), and stroke length (SL). The aim of this study is to provide an explanation for the change of SL and SR during paced exercise swimming the front crawl through an analysis of intracycle changes in motor organization.

METHODS: Trained swimmers (N = 10) swam three times to exhaustion (TTE in seconds) at predetermined velocities corresponding to 95%, 100%, and 110% of the mean speed attained in a 400-m race (V 400). During TTE tests, SR, SL, durations of the glide + catch, pull, push, and recovery phases (s) were measured. Assessment of arm coordination was made through the calculation of the index of coordination (IdC). The time allotted to propulsion per distance unit was estimated (T prop).

RESULTS: For all tested speeds, fatigue development induced a gradual increase of SR with concomitant decrease of SL. The duration of the nonpropulsive phases decreased, whereas the duration of the propulsive phases per stroke remained constant. The IdC increased reflecting a reduction of the lag time between two consecutive propulsive actions. Consequently, T prop increased.

CONCLUSION: Fatigue development induced an increase of the SR to compensate for the reduced capacity to generate a propulsive impulse per stroke. The change in arm coordination allows a better chain of the propulsive actions and leads to a greater time allotted to propulsion per distance unit. Such motor adaptation ensures that the overall propulsive impulse remained constant whereas average propulsive force per arm stroke is reduced.}, } @article {pmid19201737, year = {2009}, author = {Stevens, E and Kimler, BF and Davis, MK and Fan, F and Thomas, P and Wang, XY and Damjanov, I and Tawfik, OW}, title = {A newly proposed semi-automated method of grading invasive lobular carcinoma: a unifying concept and correlation with prognostic markers and patient survival.}, journal = {Annals of clinical and laboratory science}, volume = {39}, number = {1}, pages = {25-31}, pmid = {19201737}, issn = {1550-8080}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*pathology ; Cell Proliferation ; Chemistry, Clinical/*methods ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Survival Analysis ; }, abstract = {Invasive ductal carcinoma (IDC) of the breast is currently graded according to the Nottingham modification of the Scarff-Bloom-Richardson system (SBR). This system involves subjective evaluation of 3 morphologic features: tubule formation, nuclear pleomorphism, and mitosis. Our recently proposed semi-automated Nuclear and Proliferation Index [N+P] grading system for IDC has demonstrated agreement among grades and prognostic markers with better prediction of patient survival than the SBR system. Our present objective is to expand the utilization of the N+P system to grading invasive lobular carcinoma (ILC). Fifty-eight ILC cases were evaluated by the SBR and N+P systems. The 2 systems were compared in terms of correlation with patient survival, tumor size, grade, angiolymphatic invasion, lymph node status, ploidy status, and ER, PR, Her-2, p53, EGFR, and Bcl-2 staining. The N+P and SBR systems demonstrated overall agreement when correlated with clinical and prognostic parameters. Twenty-four of 30 tumors initially classified as SBR Grade II were down-graded to N+P I. Three of 26 tumors initially classified as SBR Grade I were up-graded to N+P II. Grading of ILC provides valuable predictive and prognostic information. The N+P grading system for ILC decreases the element of subjectivity for assessing mitotic activity and appears to be superior to the SBR system in predicting patient survival.}, } @article {pmid19201736, year = {2009}, author = {Lester, T and Wang, J and Bourne, P and Yang, Q and Fu, L and Tang, P}, title = {Different panels of markers should be used to predict mammary Paget's disease associated with in situ or invasive ductal carcinoma of the breast.}, journal = {Annals of clinical and laboratory science}, volume = {39}, number = {1}, pages = {17-24}, pmid = {19201736}, issn = {1550-8080}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*complications/pathology ; Carcinoma, Ductal, Breast/*complications/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/metabolism ; Nipples/pathology ; Paget's Disease, Mammary/*complications/*diagnosis/pathology ; }, abstract = {Mammary Paget's disease (MPD) is a rare manifestation of breast carcinoma involving the nipple. Our objective was to identify molecular markers and molecular subtypes that may predict patients at high risk of developing MPD. Immunohistochemical (IHC) analyses were performed with antibodies to estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, epidermal growth factor receptor (EGFR), and several cytokeratins (CK5/6, CK14, CK17, CK8, CK18) on representative sections of 121 cases of ductal carcinoma of the breast, including 28 cases with MPD, 81 cases with neither MPD nor nipple involvement, and 12 cases of non-MPD with nipple involvement. The rates of receptor expression and subtype distributions of 3 IHC-based molecular classifications were compared among these groups. The results showed that: (1) MPD is more likely to be associated with ER- and PR-negative ductal carcinoma in situ (DCIS), but not invasive ductal carcinoma (IDC); (2) MPD is more likely to be associated with HER2-over expression subtype DCIS, but not IDC; and (3) carcinomas with non-MPD nipple involvement differ from those with MPD, since they are more likely to be ER- and PR-positive, HER2-negative, and luminal A subtype. In summary, different panels of markers should be used to predict MPD associated with different underlying lesions; for DCIS, the ER-negative, PR-negative, and HER2-subtype and not basal-like subtype is most predictive of MPD; for IDC, the luminal B-subtype is most predictive of MPD.}, } @article {pmid19190531, year = {2009}, author = {McGonagle, D and Aziz, A and Dickie, LJ and McDermott, MF}, title = {An integrated classification of pediatric inflammatory diseases, based on the concepts of autoinflammation and the immunological disease continuum.}, journal = {Pediatric research}, volume = {65}, number = {5 Pt 2}, pages = {38R-45R}, doi = {10.1203/PDR.0b013e31819dbd0a}, pmid = {19190531}, issn = {1530-0447}, mesh = {Adaptation, Physiological/immunology ; Child ; Humans ; Immune System Diseases/*immunology ; Immunity, Innate ; Inflammation/*classification/immunology ; }, abstract = {Historically, pediatric inflammatory diseases were viewed as autoimmune but developments in genetics of monogenic disease have supported our proposal that "inflammation against self" be viewed as an immunologic disease continuum (IDC), with genetic disorders of adaptive and innate immunity at either end. Innate immune-mediated diseases may be associated with significant tissue destruction without evident adaptive immune responses and are designated as autoinflammatory due to distinct immunopathologic features. However, the majority of pediatric inflammatory disorders are situated along this IDC. Innate immunity has been demonstrated in polygenic disorders, particularly Crohn's disease (CD). A genetic overlap exists between CD and some major histocompatibility complex (MHC) class I-associated diseases, including psoriasis; these diseases seem to represent a true intermediate between autoinflammation and autoimmunity. Conversely, classical autoimmune diseases, with autoantibody and MHC class II associations, including celiac disease and rheumatoid arthritis (RA), have adaptive immune genetic associations, including Cytotoxic T-Lymphocyte Antigen-4 (CTLA4) and PTPN22. This proposed classification is clinically relevant, because innate immune-mediated disorders may respond to cytokine antagonism whereas autoimmune-mediated diseases respond better to anti-T and B cell therapies. Furthermore, the etiopathogenesis of poorly defined "autoimmune" diseases, such as juvenile idiopathic arthritis, may be inferred to have substantial innate immune involvement, based on response to IL-1 antagonism.}, } @article {pmid19190350, year = {2009}, author = {Nagasaki, S and Suzuki, T and Miki, Y and Akahira, J and Kitada, K and Ishida, T and Handa, H and Ohuchi, N and Sasano, H}, title = {17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma: a prognostic factor via potential regulation of fatty acid synthesis.}, journal = {Cancer research}, volume = {69}, number = {4}, pages = {1392-1399}, doi = {10.1158/0008-5472.CAN-08-0821}, pmid = {19190350}, issn = {1538-7445}, mesh = {17-Hydroxysteroid Dehydrogenases/genetics/*metabolism ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal/*enzymology/genetics/pathology ; Cell Division ; Estradiol/metabolism ; Fatty Acids/biosynthesis ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Prognosis ; RNA Interference ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; }, abstract = {17beta-Hydroxysteroid dehydrogenase type 12 (17beta-HSD12) has been shown to be involved in elongation of very long chain fatty acid (VLCFA) as well as in biosynthesis of estradiol (E2). 17beta-HSD12 expression was also reported in breast carcinomas but its functions have remained unknown. In this study, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases. No significant correlations were detected between 17beta-HSD12 expression and E2 concentration. We then immunolocalized this enzyme in 110 cases of invasive ductal carcinoma. 17beta-HSD12 immunoreactivity in breast carcinoma cells was significantly associated with poor prognosis of the patients. We further examined the biological significance of 17beta-HSD12 using cell-based studies. Small interfering RNA-mediated knockdown of 17beta-HSD12 in SK-BR-3 (estrogen receptor-negative breast carcinoma cell line) resulted in significant growth inhibition, which was recovered by the addition of VLCFAs such as arachidonic acid. The status of 17beta-HSD12 immunoreactivity was also correlated with adverse clinical outcome in cyclooxygenase 2 (COX2)-positive breast cancer patients but not in COX2-negative patients. Therefore, these findings indicated that 17beta-HSD12 was not necessarily related to intratumoral E2 biosynthesis, at least in human breast carcinoma, but was rather correlated with production of VLCFAs such as arachidonic acid, which may subsequently be metabolized to prostaglandins by COX2 and result in tumor progression of the patients.}, } @article {pmid19187537, year = {2009}, author = {Ma, XJ and Dahiya, S and Richardson, E and Erlander, M and Sgroi, DC}, title = {Gene expression profiling of the tumor microenvironment during breast cancer progression.}, journal = {Breast cancer research : BCR}, volume = {11}, number = {1}, pages = {R7}, pmid = {19187537}, issn = {1465-542X}, support = {R01 CA112021/CA/NCI NIH HHS/United States ; R01-CA 112021-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; Disease Progression ; Epithelial Cells/*metabolism/pathology ; Extracellular Matrix/metabolism/pathology ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunoenzyme Techniques ; Lasers ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells/*metabolism/pathology ; }, abstract = {INTRODUCTION: The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma.

METHODS: We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed.

RESULTS: Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response.

CONCLUSIONS: Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.}, } @article {pmid19185109, year = {2009}, author = {Zhou, M and Johnson, N and Gruner, S and Ecklund, GW and Meunier, P and Bryn, S and Glissmeyer, M and Steinbock, K}, title = {Clinical utility of breast-specific gamma imaging for evaluating disease extent in the newly diagnosed breast cancer patient.}, journal = {American journal of surgery}, volume = {197}, number = {2}, pages = {159-163}, doi = {10.1016/j.amjsurg.2008.10.002}, pmid = {19185109}, issn = {1879-1883}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging ; Female ; Gamma Rays ; Humans ; Middle Aged ; Radionuclide Imaging ; Radiopharmaceuticals ; Retrospective Studies ; Technetium Tc 99m Sestamibi ; }, abstract = {BACKGROUND: Breast-specific gamma imaging (BSGI) is a functional imaging modality that has comparable sensitivity but superior specificity compared with magnetic resonance imaging, yielding fewer false-positive results and thereby improving clinical management of the newly diagnosed breast cancer patient.

METHODS: A retrospective review was performed from 2 community-based breast imaging centers of newly diagnosed breast cancer patients in whom BSGI was performed as part of the imaging work-up.

RESULTS: A total of 138 patients (69 invasive ductal carcinoma, 20 invasive lobular carcinoma, 32 ductal carcinoma in situ, and 17 mixtures of invasive ductal carcinoma, invasive lobular carcinoma, or ductal carcinoma in situ and other) were reviewed. Twenty-five patients (18.1%) had a positive BSGI study at a site remote from their known cancer or more extensive disease than detected from previous imaging. Fifteen patients (10.9%) were positive for a synchronous or more extensive malignancy in the same or contralateral breast. Five patients had benign findings on pathology, 5 benign on ultrasound follow-up (false-positive rate, 7.2%). Findings converted 7 patients to mastectomy, 1 patient to neoadjuvant chemotherapy, and 7 patients were found to have previously undetected contralateral cancer. The positive predictive value for BSGI was 92.9%.

CONCLUSIONS: BSGI detected additional or more extensive malignancy in the same or contralateral breast in 10.9% of newly diagnosed breast cancer patients. Only 7.2% incurred an additional work-up. BSGI provides accurate evaluation of remaining breast tissue in newly diagnosed breast cancer patients with few false-positive readings.}, } @article {pmid19184279, year = {2009}, author = {Yoichi, T and Nagashima, T and Yagata, H and Yoshida, K and Suzuki, M and Fujimori, T and Sangai, T and Nakatani, Y and Miyazaki, M}, title = {Breast cancer with cartilaginous and/or osseous metaplasia.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {3}, pages = {234-237}, doi = {10.1007/s12282-008-0090-8}, pmid = {19184279}, issn = {1880-4233}, mesh = {Bone and Bones/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Cartilage/pathology ; Fatal Outcome ; Female ; Humans ; Magnetic Resonance Imaging ; Mastectomy ; Metaplasia/*pathology ; Middle Aged ; Phyllodes Tumor/*pathology/surgery ; Sentinel Lymph Node Biopsy ; }, abstract = {We report a rare case of breast cancer with cartilaginous and/or osseous metaplasia. A 59-year-old woman had a large lump in her left breast, which had enlarged gradually over a period of 2 years. Mammography, ultrasonography and aspiration cytology suggested phyllodes tumor with carcinoma. She underwent wide excision and sentinel lymph node biopsy. Because of the existence metastatic tumor cells in the sentinel lymph node on frozen section, sequential axillary lymph node dissection was conducted consequently. Histologically, the tumor consisted of invasive ductal carcinoma and spindle-cell carcinoma, including cartilaginous metaplasia. Adjuvant chemotherapy and whole-breast irradiation were performed. However, she died of multiple metastases to the liver 2 years after surgery. Breast cancer with cartilaginous and/or osseous metaplasia belongs to a special type of invasive carcinoma, and the incidence is very low. We here present our case and a review of the literature.}, } @article {pmid19181339, year = {2009}, author = {Masannat, YA and Hanby, A and Horgan, K and Hardie, LJ}, title = {DNA damaging effects of the dyes used in sentinel node biopsy: possible implications for clinical practice.}, journal = {The Journal of surgical research}, volume = {154}, number = {2}, pages = {234-238}, doi = {10.1016/j.jss.2008.07.039}, pmid = {19181339}, issn = {1095-8673}, mesh = {Breast Neoplasms/*pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Coloring Agents/*toxicity ; *DNA Damage ; Epithelial Cells/drug effects/*pathology ; Humans ; In Vitro Techniques ; Indigo Carmine/toxicity ; Methylene Blue/toxicity ; Rosaniline Dyes/toxicity ; *Sentinel Lymph Node Biopsy ; }, abstract = {OBJECTIVE: This study investigates whether methylene blue (MB), patent blue V (PBV), and indigo carmine (IDC) commonly used in sentinel node biopsy cause DNA damage to breast epithelial cells in vitro.

METHODS: MCF-7 and HB-2 cells were exposed for 5 minutes to the above dyes at the same concentrations used in clinical practice. Following exposure, the comet assay was performed to detect DNA damage. The enzyme, Fapy-DNA glycosylase (FpG) was incorporated to enable the detection of additional oxidative damage.

RESULTS: Both PBV and MB stimulated DNA strand breaks in both MCF-7 and HB2 cell lines (P < 0.05). Levels were elevated over 3-fold (P < 0.05) in MCF-7 and HB2 cells treated with 2.5% PBV and 1% MB, compared with untreated control cells. In contrast, IDC did not stimulate DNA strand break damage at clinically relevant concentrations in either cell line. Addition of Fapy-DNA glycosylase enzyme also revealed significantly (P < 0.05) increased levels of oxidative DNA lesions (ODL) in MCF-7 cells treated with PBV (17.6% ODL) compared with control cells (5.9% ODL).

CONCLUSIONS: This study shows, for the first time, that certain dyes (MB and PBV) commonly used in SLNB have genotoxic effects on breast cells at clinically relevant concentrations in vitro. In vivo studies are now warranted to assess and minimize DNA damage caused by these dyes during SLNB.}, } @article {pmid19173804, year = {2008}, author = {Bi, Y and Wei, L and Mao, HT and Zhang, L and Zuo, WS}, title = {[Expressions of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma and their relationship with clinicopathological factors].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {30}, number = {10}, pages = {749-753}, pmid = {19173804}, issn = {0253-3766}, mesh = {Adult ; Aged ; Antigens, CD/genetics/*metabolism ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; CTLA-4 Antigen ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; GTP-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; fas Receptor/genetics/*metabolism ; }, abstract = {OBJECTIVE: The purpose of this study was to explore the clinical significance of expression of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma.

METHODS: Semi-quantitative reverse transcriptive polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the three genes in tumor tissues from 60 patients with primary breast cancer and normal breast tissues of 30 cases. The relationship between gene expression and clinicopathological factors were analyzed and determined.

RESULTS: The relative expression levels (gray scale ratio between target gene and internal reference gene) of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma tissues were 0.699 +/- 0.285, 1.045 +/- 0.302 and 0.625 +/- 0.160, respectively. In the normal breast tissues, they were 0.502 +/- 0.178, 0.418 +/- 0.140 and 0.843 +/- 0.218, respectively. There were statistically significant differences of the expression of those three genes between carcinoma tissues and normal breast tissues (P < 0.01). The expression level of Fas in carcinoma tissues was significantly higher in lymph node matastasis positive patients (0.782 +/- 0.313) than that in node-negative patients (0.557 +/- 0.146, P < 0.01). The expression level of CTLA-4 gene in carcinoma tissues was lower in II stage patients (0.978 +/- 0.330) than that in III stage patients (1.134 +/- 0.240, P < 0.05). The expression level of RhoBTB2 gene was lower in invasive ductal carcinoma (0.597 +/- 0.157) than that in invasive lobular carcinoma (0.717 +/- 0.145, P < 0.05). There were no correlations of expression of the three genes at mRNA level and age, ER, PR, HER2 status and survival time. Furthermore, no correlation was seen among the three genes expression (P > 0.05).

CONCLUSION: The expression of all the three genes at mRNA level is involved in genesis and progression of breast cancer. There exist correlations between Fas expression and axillary lymph node matastasis, CTLA-4 expression and disease stage, and RhoBTB2 expression and pathological type of breast cancer.}, } @article {pmid19164238, year = {2009}, author = {Naya, M and Tsukamoto, T and Morita, K and Katoh, C and Nishijima, K and Komatsu, H and Yamada, S and Kuge, Y and Tamaki, N and Tsutsui, H}, title = {Myocardial beta-adrenergic receptor density assessed by 11C-CGP12177 PET predicts improvement of cardiac function after carvedilol treatment in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {50}, number = {2}, pages = {220-225}, doi = {10.2967/jnumed.108.056341}, pmid = {19164238}, issn = {0161-5505}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Aged ; Carbazoles/*therapeutic use ; *Carbon Radioisotopes ; Cardiomyopathy, Dilated/*diagnostic imaging/*drug therapy/physiopathology ; Carvedilol ; Dobutamine ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Myocardium/metabolism ; Positron-Emission Tomography ; Prognosis ; Propanolamines/*therapeutic use ; *Radiopharmaceuticals ; Receptors, Adrenergic, beta/*metabolism ; Stroke Volume/drug effects ; }, abstract = {UNLABELLED: We evaluated whether myocardial beta-adrenergic receptor (beta-AR) density, as determined by 11C-CGP12177 PET, could predict improvement of cardiac function by beta-blocker carvedilol treatment in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS: Ten patients with IDC (left ventricular ejection fraction [LVEF]<45%) were studied. Myocardial beta-AR density was estimated using 11C-CGP12177 PET before treatment with carvedilol. Changes of LVEF in response to dobutamine infusion (DeltaLVEF-dobutamine) were also measured by echocardiography. Changes of LVEF (DeltaLVEF-carvedilol) were evaluated after 20 mo of carvedilol treatment.

RESULTS: Baseline myocardial beta-AR density significantly correlated with DeltaLVEF-carvedilol (r=-0.88, P<0.001). In contrast, DeltaLVEF-dobutamine did not correlate with DeltaLVEF-carvedilol (P=0.65). Myocardial beta-AR density was the significant multivariate independent predictor of DeltaLVEF-carvedilol (beta=-0.88, P<0.001) among univariate predictors, including functional class (r=0.76, P<0.05), plasma norepinephrine (r=0.85, P<0.01), LVEF (r=-0.64, P<0.05), and age as confounding factors. Furthermore, myocardial beta-AR density was significantly correlated with plasma norepinephrine (r=-0.79, P<0.01) and LVEF (r=0.70, P<0.05).

CONCLUSION: Myocardial beta-AR density is more tightly related to improvement of LVEF-carvedilol than is cardiac contractile reserve in patients with IDC. Patients with decreased myocardial beta-AR have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may receive greater benefit from being treated by antiadrenergic drugs.}, } @article {pmid19161612, year = {2009}, author = {Lanitis, S and Sivakumar, S and Behranwala, K and Zacharakis, E and Al Mufti, R and Hadjiminas, DJ}, title = {A case of Meigs syndrome mimicking metastatic breast carcinoma.}, journal = {World journal of surgical oncology}, volume = {7}, number = {}, pages = {10}, pmid = {19161612}, issn = {1477-7819}, mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms/blood/*diagnosis ; CA-125 Antigen/blood ; Carcinoma, Ductal, Breast/blood/*diagnosis ; Diagnosis, Differential ; Female ; Fibroma/*diagnosis/drug therapy ; Gynecologic Surgical Procedures ; Humans ; Letrozole ; Mastectomy ; Meigs Syndrome/blood/*diagnosis/therapy ; Middle Aged ; Nitriles/therapeutic use ; Ovarian Neoplasms/*diagnosis/drug therapy ; Pleural Effusion/diagnosis/drug therapy ; Triazoles/therapeutic use ; }, abstract = {BACKGROUND: Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity.

CASE PRESENTATION: A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma.

CONCLUSION: Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.}, } @article {pmid19159568, year = {2008}, author = {Liu, RB and Zhou, XH and Wang, JN and Liang, HZ and Li, XX and Wu, ZH and Ye, JL and Wang, SM}, title = {[Expression of estrogen receptor, progesterone receptor, and human epithelial growth factor receptor 2 in breast cancer and the significance thereof: analysis of 910 cases].}, journal = {Zhonghua yi xue za zhi}, volume = {88}, number = {48}, pages = {3397-3400}, pmid = {19159568}, issn = {0376-2491}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Estrogen Receptor alpha/*metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Progesterone/*metabolism ; Retrospective Studies ; }, abstract = {OBJECTIVE: To investigate the expression of estrogen receptor (ER), progesterone receptor (PR), and human epithelial growth factor receptor 2 (HER2) in breast cancer, and to explore their correlation with the age of patient, and size, clinic stage, and lymph node metastasis of the tumor.

METHODS: The data of 910 breast cancer, 89.4% of invasive ductal carcinoma, 1.7% of invasive lobular carcinoma, 44 cases 5% of ductal carcinoma in situ, and 4.9% of other pathologic types, 29.9% being less than 2 cm, 45.6% being 2-5 cm, and 24.5% bigger than 5 cm in size, 54.2% without metastasis in lymph node, 25.5% with metastasis in 1-3 lymph nodes, and 20.3% with metastasis in more than 3 lymph nodes respectively, were analyzed retrospectively. Immunohistochemistry was used to detect the expression of ER, PR, and HER2.

RESULTS: The ER negative expression rate was 33.0%, and PR negative expression rate was 27.4%, and HER2 overexpression rate was 20.3%. The possibility of lymph node metastasis decreased along with the increase of age (P < 0.001). Tumor size was negatively correlated with the expression of ER and PR (both P < 0.001), and positively correlated with the expression of HER2 (P < 0.001). There was no significant difference between the situation of lymph node metastasis and the expression of ER, PR and HER2 in primary tumors.

CONCLUSION: As good prognostic markers of breast invasive ductal cancer, ER and PR are negatively correlated with the HER2 expression, as a worse prognostic marker. ER/PR positive or HER2 negative tumors are morel likely to be diagnosed at earlier stages.}, } @article {pmid19156836, year = {2009}, author = {Natrajan, R and Lambros, MB and Geyer, FC and Marchio, C and Tan, DS and Vatcheva, R and Shiu, KK and Hungermann, D and Rodriguez-Pinilla, SM and Palacios, J and Ashworth, A and Buerger, H and Reis-Filho, JS}, title = {Loss of 16q in high grade breast cancer is associated with estrogen receptor status: Evidence for progression in tumors with a luminal phenotype?.}, journal = {Genes, chromosomes & cancer}, volume = {48}, number = {4}, pages = {351-365}, doi = {10.1002/gcc.20646}, pmid = {19156836}, issn = {1098-2264}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/*metabolism/pathology ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 16/*genetics ; Cluster Analysis ; Comparative Genomic Hybridization ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Genomic Instability ; Humans ; Immunohistochemistry ; Male ; Receptors, Estrogen/genetics/*metabolism ; }, abstract = {Loss of the long arm of chromosome 16 (16q) is observed in the vast majority of low grade/grade I (GI) invasive ductal carcinomas of no special type (IDC-NSTs), whereas this event is uncommonly seen in high grade/grade III (GIII) IDC-NSTs. Together with data on the pathology and genetics of breast cancer recurrences, this has led to the proposal that GI and GIII breast cancers evolve through distinct genetic pathways and that progression from GI to GIII is an unlikely biological phenomenon. We compared the genomic profiles of GIII-IDC-NSTs with 16q whole arm loss (16qWL) according to estrogen receptor (ER) status. 16qWL was found in 36.5% of cases and was significantly associated with ER expression and luminal phenotype. ER+ GIII-IDC-NSTs with 16qWL displayed significantly higher levels of genomic instability than ER+ IDC-NSTs without 16qWL. Furthermore, ER+ and ER- IDC-NSTs stratified according to the presence of 16qWL harbored distinct patterns of genetic aberrations. Interestingly, ER+/16qWL tumors displayed genetic features usually found in tumors with homologous DNA repair defects and significantly more frequently harbored heterozygous loss of BRCA2 than the remaining ER+ cancers. Our results demonstrate that approximately one third of GIII tumors harbor 16qWL, confirming that progression from low to high grade breast cancer is not found in the majority of breast cancers. 16qWL was significantly more prevalent in ER+/luminal GIII-IDC-NSTs. Given that GI breast cancers harbor a luminal phenotype, our results suggest that if progression from GI to GIII breast cancer does happen, it may preferentially occur in breast cancers of luminal phenotype.}, } @article {pmid19154512, year = {2009}, author = {Weerakoon, M and Lawrentschuk, N}, title = {Draping and associated equipment for indwelling catheter manipulation by hospital staff: an assessment of attitudes and adequacy.}, journal = {BJU international}, volume = {103}, number = {9}, pages = {1206-1209}, doi = {10.1111/j.1464-410X.2008.08248.x}, pmid = {19154512}, issn = {1464-410X}, mesh = {*Attitude of Health Personnel ; *Bedding and Linens ; Catheters, Indwelling/adverse effects/*standards ; Equipment Failure ; Humans ; Infection Control/methods/*standards ; Medical Waste Disposal ; Occupational Exposure/*adverse effects ; Safety Management ; Surveys and Questionnaires ; Urinary Catheterization/adverse effects/*standards ; }, abstract = {OBJECTIVE: To address the usability and safety aspects of current equipment for indwelling urinary catheter (IDC) manipulation, by assessing the attitudes of doctors and nurses to infection control, occupational health and environmental waste, and the perceived adequacy of available catheter packs, particularly drapes, when performing such manipulations.

SUBJECTS AND METHODS: A self-administered survey instrument was created using an online database and completed by doctors and nurses. The survey covered basic demographics and experience with IDC, attitudes to infection control, occupational health and safety, and the environment, as well as adequacy of current equipment in containing spillage of urine and/or blood.

RESULTS: In all, 87 doctors and 228 nurses completed 315 of 350 (90%) surveys. Doctors and nurses were concerned about infection control, occupational health and safety issues, and environmental waste. Incidents involving spillage of urine and/or blood often go unreported. There were no differences between nurses and doctors having specialist training in urology or experience (P > 0.05). The second major finding is that available catheter packs, particularly drapes, when manipulating IDCs, are inadequate and spillage is likely. These findings were more pronounced in doctors and those with urology training (P < 0.05).

CONCLUSION: The attitudes of health professionals involved with IDC manipulations are consistent with other fields, as is the under-reporting of episodes of contamination by bodily fluids. The current equipment, particularly drapes, are inadequate for containing urine and blood, leading to infection control, occupational health, environmental and cost implications.}, } @article {pmid19154262, year = {2009}, author = {Kurokawa, K and Mouri, Y and Asano, A and Kamei, K and Iwata, Y and Isogai, M and Saga, S and Ichihara, S}, title = {Pleomorphic carcinoma with osteoclastic giant cells of the breast: immunohistochemical differentiation between coexisting neoplastic and reactive giant cells.}, journal = {Pathology international}, volume = {59}, number = {2}, pages = {91-97}, doi = {10.1111/j.1440-1827.2008.02334.x}, pmid = {19154262}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*diagnosis ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Giant Cell/chemistry/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/chemistry/pathology ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Giant Cells/chemistry/*pathology ; Humans ; Immunohistochemistry ; Mastectomy, Simple ; Middle Aged ; Neoplasms, Complex and Mixed/chemistry/*diagnosis ; Osteoclasts/chemistry/*pathology ; Treatment Outcome ; }, abstract = {Herein is described a unique case of breast carcinoma with two different types of giant cells noted in both cytological and histological specimens. A 51-year-old Japanese woman noticed a hard mass in the upper outer quadrant of her left breast. Aspiration cytology exhibited numerous anaplastic giant cells; the cytological diagnosis was high-grade ductal carcinoma, although a few osteoclastic giant cells were also observed. A left simple mastectomy and sentinel lymph node biopsy were performed. Histologically, approximately 90% of the tumor was composed of giant cells; conventional invasive ductal carcinoma and ductal carcinoma in situ were found focally at the periphery of the tumor. The main part of the tumor contained both anaplastic, neoplastic giant cells and non-neoplastic, osteoclastic giant cells that were distinguishable from nuclear atypism. The presence of the two types of giant cells was also confirmed on immunohistochemistry using a histiocytic marker (CD68) and two epithelial markers (AE1/AE3 and CAM5.2). Based on the latest World Health Organization classification, the diagnosis was pleomorphic carcinoma with osteoclastic giant cells. To the authors' knowledge there has been no previous report on this subject except for a single case mentioned in Rosen's Breast Pathology.}, } @article {pmid19153424, year = {2008}, author = {Irawan, C and Hukom, R and Prayogo, N}, title = {Factors associated with bone metastasis in breast cancer: a preliminary study in an Indonesian population.}, journal = {Acta medica Indonesiana}, volume = {40}, number = {4}, pages = {178-180}, pmid = {19153424}, issn = {0125-9326}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Bone Neoplasms/epidemiology/genetics/*secondary ; Breast Neoplasms/epidemiology/genetics/*pathology ; Cathepsin D/metabolism ; Chi-Square Distribution ; Cross-Sectional Studies ; Estrogen Replacement Therapy ; Female ; Humans ; Indonesia/epidemiology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; }, abstract = {AIM: to know the characteristics of breast cancer patients with bone metastasis and its risk factors.

METHODS: this was a cross-sectional study on breast cancer patients in Dharmais Cancer Hospital between 1998 and 2002. Data were retrieved from medical records and consisted of age, history of hormonal contraceptive use, histopathological type, estrogen receptor (ER) and progesteron receptor (PR) expression, c-erbB-2 and cathepsin D expressions.

RESULTS: a total of 197 cases were recruited between the study period. Almost all patients were women with a mean age of 47 years old. The majority of patients were between 36 and 55 years old (69.1%) with a peak between 46 and 50 years. About 70% of the patients had already had advanced diseases (III and IV). Invasive ductal carcinoma was the commonest histopathological type (80%). The expression of ER, PR, c-erbB-2, and cathepsin D were evaluated in 55 patients. Metastases were found to occur in bone (24.4%), lungs (20.8%), and liver (10.7%). Among patients with bone metastasis, 36 patients ((75%) were more than 40 years old and 32 (66.7%) had invasive ductal carcinomas. There was a significant correlation (p=0.011) between bone metastasis and histopathological type. No significant correlation was found between the use of hormonal contraceptives, ER/PR expression, c-erbB-2 and cathepsin D and bone metastasis.

CONCLUSION: most breast cancer patients came in an already advanced stage, either locally or distant metastasis. The most common site of metastasis was the bone, followed by lungs and liver. Histopathological type of invasive ductal carcinoma was associated to the higher incidence of bone metastasis. Further studies are needed to identify patients with high risk of bone metastasis. There is also a need to evaluate predictive factors for the occurrence of bone metastasis at earlier stage.}, } @article {pmid19153192, year = {2009}, author = {Dietrich, D and Lesche, R and Tetzner, R and Krispin, M and Dietrich, J and Haedicke, W and Schuster, M and Kristiansen, G}, title = {Analysis of DNA methylation of multiple genes in microdissected cells from formalin-fixed and paraffin-embedded tissues.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {57}, number = {5}, pages = {477-489}, pmid = {19153192}, issn = {0022-1554}, mesh = {Adipose Tissue/chemistry/pathology ; Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/pathology ; *DNA Methylation ; Female ; Fibrocystic Breast Disease/chemistry/pathology ; *Fixatives ; *Formaldehyde ; Humans ; Indicators and Reagents ; Lasers ; Lymphocytes, Tumor-Infiltrating/chemistry ; Microdissection ; *Paraffin Embedding ; Polymerase Chain Reaction/methods ; Promoter Regions, Genetic ; Sequence Analysis, DNA/methods ; Stromal Cells/chemistry ; Sulfites ; }, abstract = {A procedure for simultaneous quantification of DNA methylation of several genes in minute amounts of sample material was developed and applied to microdissected formalin-fixed and paraffin-embedded breast tissues. The procedure is comprised of an optimized bisulfite treatment protocol suitable for samples containing only few cells, a multiplex preamplification and subsequent locus specific reamplification, and a novel quantitative bisulfite sequencing method based on the incorporation of a normalization domain into the PCR product. A real-time PCR assay amplifying repetitive elements was established to quantify low amounts of bisulfite-treated DNA. Ten prognostic and diagnostic epigenetic breast cancer biomarkers (PITX2, RASSF1A, PLAU, LHX3, PITX3, LIMK1, SLITRK1, SLIT2, HS3ST2, and TFF1) were analyzed in tissue samples obtained from two patients with invasive ductal carcinoma of the breast. The microdissected samples were obtained from several areas within the tumor tissue, including intraductal and invasive carcinoma, adenosis, and normal ductal epithelia of adjacent normal tissue, as well as stroma, tumor infiltrating lymphocytes, and adipose tissue. Overall, reliable quantification was possible for all genes. For most genes, increased DNA methylation in invasive and intraductal carcinoma cells compared with other tissue components was observed. For TFF1, decreased methylation levels were observed in tumor cells.}, } @article {pmid19152796, year = {2009}, author = {Heo, YJ and Son, CH and Chung, JS and Park, YS and Son, JH}, title = {The cryopreservation of high concentrated PBMC for dendritic cell (DC)-based cancer immunotherapy.}, journal = {Cryobiology}, volume = {58}, number = {2}, pages = {203-209}, doi = {10.1016/j.cryobiol.2008.12.006}, pmid = {19152796}, issn = {1090-2392}, mesh = {Cell Differentiation ; Cell Survival ; Cells, Cultured ; Cryopreservation/instrumentation/*methods ; Dendritic Cells/*cytology/*immunology ; Humans ; Immunotherapy ; Leukocytes, Mononuclear/*cytology/immunology ; Lymphocyte Activation/immunology ; Time Factors ; }, abstract = {Peripheral blood mononuclear cells (PBMC) have been accepted as a unique material for cancer immunotherapy using dendritic cells (DC) or activated lymphocytes that are being developed as an alternative or adjuvant to conventional therapies such as surgery, chemotherapy and radiation treatment. Although successful cryopreservation of large numbers of PBMC is critical for the immunotherapy, subsequent functional study of the effects of PBMC cryopreservation on differentiation into immune cells has not been well defined. In this study, over 1.0 x 10(8)cells/ml PBMC were cryopreserved as long as 52 weeks using a controlled-rate freezer (CRF) and stored in a vapor phase of liquid nitrogen tank. The effect of PBMC cryopreservation on differentiation into DC was studied by comparing the phenotypic and functional properties of immature DC (iDC) and mature DC (mDC) derived from cryopreserved PBMC to those from fresh PBMC. The results show that cryopreservation of PBMC at a fairly high cell concentration does not significantly affect cell recovery, viability, or phenotypes of PBMC. After differentiation into DC, iDC and mDC derived from cryopreserved PBMC had their typical phenotypes and function equivalent to those derived from fresh PBMC. Therefore, the improved cryopreservation process of PBMC described in this study is available for DC-based cancer immunotherapy.}, } @article {pmid19151330, year = {2009}, author = {Sims, JS and Militello, KT and Sims, PA and Patel, VP and Kasper, JM and Wirth, DF}, title = {Patterns of gene-specific and total transcriptional activity during the Plasmodium falciparum intraerythrocytic developmental cycle.}, journal = {Eukaryotic cell}, volume = {8}, number = {3}, pages = {327-338}, pmid = {19151330}, issn = {1535-9786}, support = {F32 AI050303/AI/NIAID NIH HHS/United States ; R01 GM061351/GM/NIGMS NIH HHS/United States ; GM61351-03/GM/NIGMS NIH HHS/United States ; AI050303-01/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Erythrocytes/*parasitology ; *Gene Expression Regulation, Developmental ; Humans ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/genetics/*growth & development/metabolism ; Protozoan Proteins/*genetics/metabolism ; *Transcription, Genetic ; }, abstract = {The relationships among gene regulatory mechanisms in the malaria parasite Plasmodium falciparum throughout its asexual intraerythrocytic developmental cycle (IDC) remain poorly understood. To investigate the level and nature of transcriptional activity and its role in controlling gene expression during the IDC, we performed nuclear run-on on whole-transcriptome samples from time points throughout the IDC and found a peak in RNA polymerase II-dependent transcriptional activity related to both the number of nuclei per parasite and variable transcriptional activity per nucleus over time. These differential total transcriptional activity levels allowed the calculation of the absolute transcriptional activities of individual genes from gene-specific nuclear run-on hybridization data. For half of the genes analyzed, sense-strand transcriptional activity peaked at the same time point as total activity. The antisense strands of several genes were substantially transcribed. Comparison of the transcriptional activity of the sense strand of each gene to its steady-state RNA abundance across the time points assayed revealed both correlations and discrepancies, implying transcriptional and posttranscriptional regulation, respectively. Our results demonstrate that such comparisons can effectively indicate gene regulatory mechanisms in P. falciparum and suggest that genes with diverse transcriptional activity levels and patterns combine to produce total transcriptional activity levels tied to parasite development during the IDC.}, } @article {pmid19144278, year = {2008}, author = {Buttari, B and Profumo, E and Mancinelli, R and Cesta Incani, U and Tosti, ME and Attilia, ML and Ceccanti, M and Riganò, R}, title = {Chronic and acute alcohol exposure prevents monocyte-derived dendritic cells from differentiating and maturing.}, journal = {International journal of immunopathology and pharmacology}, volume = {21}, number = {4}, pages = {929-939}, doi = {10.1177/039463200802100417}, pmid = {19144278}, issn = {0394-6320}, mesh = {Adolescent ; Adult ; Alcoholism/*immunology ; Cell Differentiation/*drug effects ; Dendritic Cells/*drug effects/immunology/metabolism ; Endocytosis ; Ethanol/*administration & dosage/toxicity ; Female ; Flow Cytometry ; Humans ; Lipopolysaccharides/pharmacology ; Male ; Middle Aged ; Monocytes/*cytology ; NF-kappa B/metabolism ; }, abstract = {Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics inverted exclamation mark| monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.}, } @article {pmid19141383, year = {2009}, author = {Esposito, NN and Dabbs, DJ and Bhargava, R}, title = {Are encapsulated papillary carcinomas of the breast in situ or invasive? A basement membrane study of 27 cases.}, journal = {American journal of clinical pathology}, volume = {131}, number = {2}, pages = {228-242}, doi = {10.1309/AJCP8A2UVLCYGTPU}, pmid = {19141383}, issn = {1943-7722}, mesh = {Adult ; Aged ; Aged, 80 and over ; Basement Membrane/chemistry/pathology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology ; Carcinoma, Papillary/chemistry/*pathology/surgery ; Collagen Type IV/analysis ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasms, Multiple Primary/pathology ; Retrospective Studies ; }, abstract = {Encapsulated papillary carcinoma (EPC) of the breast is traditionally considered a variant of ductal carcinoma in situ (DCIS). However, recent studies show EPCs lack myoepithelial cells at their periphery, leading some to conclude that EPCs are invasive. We used a robust collagen type IV immunohistochemical procedure to assess invasion in 21 cases of pure EPC and 6 EPCs with adjacent invasive ductal carcinoma (IDC) and compared these results with those for papilloma, DCIS, and IDC. Moderate to intense collagen type IV expression was seen in all EPCs and was absent or decreased in all IDCs. All patients with pure EPC had negative axillary nodes with the exception of 1 who had a micrometastasis, and all were alive with no evidence of disease at follow-up (mean, 40.4 months). EPCs are in situ carcinomas with an excellent prognosis and can be managed with local therapy with or without sentinel lymph node biopsy.}, } @article {pmid19135933, year = {2009}, author = {Chang, YW and Kwon, KH and Lee, DW}, title = {Synchronous bilateral mucinous carcinoma of the breast: case report.}, journal = {Clinical imaging}, volume = {33}, number = {1}, pages = {62-66}, doi = {10.1016/j.clinimag.2008.05.004}, pmid = {19135933}, issn = {1873-4499}, mesh = {Adenocarcinoma, Mucinous/*diagnosis ; Aged ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; }, abstract = {A mucinous carcinoma of the breast is a well-differentiated rare histological type of invasive ductal carcinoma, having a lower frequency of metastasis to an axillary lymph node and a better survival rate. Bilateral breast cancer has an overall incidence of 4% to 20% in patients with primary operable breast cancer. Few reports exist in the clinical literature characterizing a synchronous bilateral mucinous carcinoma of the breast. We report the characteristic imaging findings of a bilateral mucinous carcinoma of the breast.}, } @article {pmid19128816, year = {2009}, author = {Le Nouën, C and Munir, S and Losq, S and Winter, CC and McCarty, T and Stephany, DA and Holmes, KL and Bukreyev, A and Rabin, RL and Collins, PL and Buchholz, UJ}, title = {Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3.}, journal = {Virology}, volume = {385}, number = {1}, pages = {169-182}, pmid = {19128816}, issn = {1096-0341}, support = {Z99 AI999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {ADP-ribosyl Cyclase 1/metabolism ; Adult ; Animals ; Apoptosis ; Cell Line ; Cells, Cultured ; Chlorocebus aethiops ; Cytokines/metabolism ; Dendritic Cells/cytology/*virology ; Gene Expression Regulation ; Humans ; Metapneumovirus/*physiology ; Monocytes/immunology/virology ; Parainfluenza Virus 3, Human/*physiology ; Paramyxoviridae Infections/*virology ; RNA, Viral/metabolism ; Respiratory Syncytial Virus Infections/*virology ; Respiratory Syncytial Virus, Human/*physiology ; Respirovirus Infections/*virology ; Vero Cells ; Viral Fusion Proteins/genetics/immunology/metabolism ; }, abstract = {Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza virus type 3 (HPIV3) are common, important respiratory pathogens, but HRSV has a substantially greater impact with regard to acute disease, long-term effects on airway function, and frequency of re-infection. It has been reported to strongly interfere with the functioning of dendritic cells (DC). We compared HRSV to HMPV and HPIV3 with regard to their effects on human monocyte-derived immature DC (IDC). Side-by-side analysis distinguished between common effects versus those specific to individual viruses. The use of GFP-expressing viruses yielded clear identification of robustly infected cells and provided the means to distinguish between direct effects of robust viral gene expression versus bystander effects. All three viruses infected inefficiently based on GFP expression, with considerable donor-to donor-variability. The GFP-negative cells exhibited low, abortive levels of viral RNA synthesis. The three viruses induced low-to-moderate levels of DC maturation and cytokine/chemokine responses, increasing slightly in the order HRSV, HMPV, and HPIV3. Infection at the individual cell level was relatively benign, such that in general GFP-positive cells were neither more nor less able to mature compared to GFP-negative bystanders, and cells were responsive to a secondary treatment with lipopolysaccharide, indicating that the ability to mature was not impaired. However, there was a single exception, namely that HPIV3 down-regulated CD38 expression at the RNA level. Maturation by these viruses was anti-apoptotic. Inefficient infection of IDC and sub-optimal maturation might result in reduced immune responses, but these effects would be common to all three viruses rather than specific to HRSV.}, } @article {pmid19122965, year = {2008}, author = {Padungchaichote, W and Kongmebhol, P and Muttarak, M}, title = {Clinics in diagnostic imaging (125). Diagnosis: Suspicious right breast carcinoma with axillary node metastases.}, journal = {Singapore medical journal}, volume = {49}, number = {12}, pages = {1062-5; quiz 1066}, pmid = {19122965}, issn = {2737-5935}, mesh = {Axilla ; Biopsy, Needle ; Breast Neoplasms/*diagnostic imaging/pathology/secondary ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*diagnostic imaging/pathology ; Lymphatic Metastasis ; *Mammography ; Middle Aged ; Neoplasms, Second Primary/diagnostic imaging ; Ovarian Neoplasms/pathology ; }, abstract = {A 61-year-old woman who had a known history of ovarian carcinoma presented with a palpable painless mass in the right axilla. Mammograms showed segmental-distributed pleomorphic microcalcifications in the upper outer quadrant of the right breast with marked enlargement of the right axillary nodes. The biggest node contained microcalcifications. Right axillary node dissection showed metastatic adenocarcinoma which was likely to be metastasis from the primary breast carcinoma. Unfortunately, she was then lost to follow-up and came back again with a right breast mass. Histopathology of the right breast mass revealed invasive ductal carcinoma. The causes and differential diagnosis of axillary adenopathy are discussed. In a patient with known primary extramammary malignancy and axillary adenopathy, it is important to differentiate if it is metastasis from the primary breast carcinoma or extramammary malignancy to provide proper management.}, } @article {pmid19121212, year = {2009}, author = {Shen, C and Gu, M and Liang, D and Miao, L and Hu, L and Zheng, C and Chen, J}, title = {Establishment and characterization of three new human breast cancer cell lines derived from Chinese breast cancer tissues.}, journal = {Cancer cell international}, volume = {9}, number = {}, pages = {2}, pmid = {19121212}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is a major malignancy affecting females worldwide. It is the most common cause of death from cancer in women. Cell lines are widely used in laboratory research and particularly as in vitro models in cancer research. But we found that the routinely used breast cancer cell lines were mostly derived from Caucasians or African-Americans. There were few standard models to study the pathogenic mechanism at molecular level and cell signaling pathway of breast cancer for Asian patients. It is quite necessary to establish new breast cancer cell lines from xanthoderm to study the pathogenic mechanism and therapeutic methods.

RESULTS: Three new breast cancer cell lines, designated BC-019, BC-020 and BC-021, were successfully established and characterized from breast invasive ductal carcinoma tissues of three Chinese female patients. These new cell lines growing as adherent monolayer with characteristic epithelial morphology could be maintained continuously in vitro, and they were ER-, PR- and C-erbB-2-positive. Their chromosomes showed high hyperdiploidy and complex rearrangements, and they displayed aggressive tumorigencity in tumorigenesis test.

CONCLUSION: The three newly established breast cancer cell lines from Chinese patients were tested for a number of, and the results indicate that the cell lines were in good quality and could be served as new cell models in breast cancer study.}, } @article {pmid19121206, year = {2009}, author = {Gujral, DM and Quante, M and Simcock, RA}, title = {An unusual cause of dysphagia in ductal breast cancer due to submucosal oropharyngeal metastatic spread: a case report.}, journal = {Cases journal}, volume = {2}, number = {1}, pages = {3}, pmid = {19121206}, issn = {1757-1626}, abstract = {INTRODUCTION: Invasive ductal and lobular carcinomas represent 67.9% and 6.3% of breast carcinoma, respectively. Metastatic breast cancer typically involves the lungs, bones, brain, and liver. Studies have shown differing patterns of metastatic spread between ductal and lobular carcinoma. Lobular carcinoma is more likely to metastasise to the gastrointestinal tract.

CASE PRESENTATION: We report the case of a 49 year old white woman with invasive ductal carcinoma with lobular differentiation who developed submucosal oropharyngeal metastases nearly two years after her original diagnosis after presenting with odynophagia and dysphagia. The patient's symptoms preceded any associated radiological or endoscopic abnormalities by at least 9 months. Repeat computed tomography scan and eventual oropharyngeal biopsy confirmed submucosal metastatic invasive ductal carcinoma, suggesting occult submucosal spread.

CONCLUSION: This case illustrates the importance of maintaining a high index of suspicion for metastatic disease in patients with invasive breast cancer who present with unusual symptoms and a careful search for metastatic sites.}, } @article {pmid19121176, year = {2008}, author = {Bubenik, L and Hosgood, G}, title = {Urinary tract infection in dogs with thoracolumbar intervertebral disc herniation and urinary bladder dysfunction managed by manual expression, indwelling catheterization or intermittent catheterization.}, journal = {Veterinary surgery : VS}, volume = {37}, number = {8}, pages = {791-800}, doi = {10.1111/j.1532-950X.2008.00452.x}, pmid = {19121176}, issn = {1532-950X}, mesh = {Animals ; Dog Diseases/*therapy ; Dogs ; Female ; Intervertebral Disc Displacement/complications/therapy/*veterinary ; Male ; Risk Factors ; Time Factors ; Treatment Outcome ; Urinary Bladder Diseases/complications/therapy/*veterinary ; Urinary Catheterization/adverse effects/methods/*veterinary ; Urinary Tract Infections/epidemiology/etiology/*veterinary ; Urination/physiology ; }, abstract = {OBJECTIVE: To evaluate risk factors for lower urinary tract infection (UTI) in dogs with intervertebral disc disease (IVDD) that had manual expression (ME), indwelling catheterization (IDC) or intermittent catheterization (ITC) for urinary bladder management.

STUDY DESIGN: Randomized-clinical trial.

ANIMALS: Dogs (n=62) treated with urinary bladder dysfunction requiring surgery for IVDD and control dogs (n=30) that had surgery for reasons other than IVDD.

METHODS: Treated dogs were randomly assigned to ME, IDC, or ITC. Urine was collected for culture and antimicrobial susceptibility testing before and after treatment. Incidence and risk factors for UTI were evaluated. Bacterial isolates and antimicrobial resistance patterns were described.

RESULTS: Mean (+/-SD) time to urination was significantly longer for IDC dogs (7.4+/-2.75 days) than ME dogs (4.2+/-2.63) and ITC dogs (4.9+/-3.12). Thirteen treated dogs (21%) and no control dogs developed UTI: 4/25 (16%) ME, 8/25 (32%) IDC, and 1/12 (8%) ITC. Enterobacter sp. was most frequently isolated (4/13; 31%). Duration of treatment was the only risk factor for UTI and each additional day of treatment increased the risk of UTI 1.5 times.

CONCLUSION: For dogs with acute IVDD, the duration of required urinary bladder management establishes the risk of UTI, not the urinary bladder management technique.

CLINICAL RELEVANCE: Duration of treatment for urinary bladder dysfunction is a risk factor for UTI in dogs recovering from acute IVDD. Treatment for urinary bladder management should be limited where possible and no method of treatment is preferred. For dogs managed by IDC, voluntary urination might occur before clinically suspected.}, } @article {pmid19119011, year = {2009}, author = {Csankovszki, G and Collette, K and Spahl, K and Carey, J and Snyder, M and Petty, E and Patel, U and Tabuchi, T and Liu, H and McLeod, I and Thompson, J and Sarkeshik, A and Yates, J and Meyer, BJ and Hagstrom, K}, title = {Three distinct condensin complexes control C. elegans chromosome dynamics.}, journal = {Current biology : CB}, volume = {19}, number = {1}, pages = {9-19}, pmid = {19119011}, issn = {1879-0445}, support = {R01 GM079533/GM/NIGMS NIH HHS/United States ; R01 GM030702/GM/NIGMS NIH HHS/United States ; T32 GM07544/GM/NIGMS NIH HHS/United States ; P41 RR011823/RR/NCRR NIH HHS/United States ; R01 GM076378/GM/NIGMS NIH HHS/United States ; R01 GM30702/GM/NIGMS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; R01 GM030702-28/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Triphosphatases/*genetics/metabolism/*physiology ; Animals ; Caenorhabditis elegans/*genetics/physiology ; Cell Nucleus Division/physiology ; Chromosome Segregation/*physiology ; Chromosomes/*genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism/*physiology ; Dosage Compensation, Genetic/*genetics/physiology ; Evolution, Molecular ; Gene Expression Regulation/*genetics/physiology ; Immunoprecipitation ; *Models, Biological ; Multiprotein Complexes/*genetics/metabolism/*physiology ; Proteomics/methods ; RNA Interference ; }, abstract = {BACKGROUND: Condensin complexes organize chromosome structure and facilitate chromosome segregation. Higher eukaryotes have two complexes, condensin I and condensin II, each essential for chromosome segregation. The nematode Caenorhabditis elegans was considered an exception, because it has a mitotic condensin II complex but appeared to lack mitotic condensin I. Instead, its condensin I-like complex (here called condensin I(DC)) dampens gene expression along hermaphrodite X chromosomes during dosage compensation.

RESULTS: Here we report the discovery of a third condensin complex, condensin I, in C. elegans. We identify new condensin subunits and show that each complex has a conserved five-subunit composition. Condensin I differs from condensin I(DC) by only a single subunit. Yet condensin I binds to autosomes and X chromosomes in both sexes to promote chromosome segregation, whereas condensin I(DC) binds specifically to X chromosomes in hermaphrodites to regulate transcript levels. Both condensin I and II promote chromosome segregation, but associate with different chromosomal regions during mitosis and meiosis. Unexpectedly, condensin I also localizes to regions of cohesion between meiotic chromosomes before their segregation.

CONCLUSIONS: We demonstrate that condensin subunits in C. elegans form three complexes, one that functions in dosage compensation and two that function in mitosis and meiosis. These results highlight how the duplication and divergence of condensin subunits during evolution may facilitate their adaptation to specialized chromosomal roles and illustrate the versatility of condensins to function in both gene regulation and chromosome segregation.}, } @article {pmid20635772, year = {2009}, author = {Doron, G and Moulding, R}, title = {Cognitive behavioral treatment of obsessive compulsive disorder: a broader framework.}, journal = {The Israel journal of psychiatry and related sciences}, volume = {46}, number = {4}, pages = {257-263}, pmid = {20635772}, issn = {0333-7308}, mesh = {Cognitive Behavioral Therapy/*methods ; Combined Modality Therapy ; Cross-Sectional Studies ; Culture ; Health Education/methods ; Humans ; Implosive Therapy/methods ; Obsessive-Compulsive Disorder/epidemiology/psychology/*therapy ; Professional-Patient Relations ; Reality Testing ; Secondary Prevention ; Self Concept ; }, abstract = {Obsessive Compulsive Disorder (OCD) is rated as a leading cause of disability by the World Health Organization (1996). OCD is a heterogeneous and complex anxiety disorder characterized by the occurrence of repeated and distressing intrusive thoughts, and compulsive actions that are performed in order to lessen distress or prevent the negative outcome associated with the intrusions. Over the last several decades, cognitive behavioral treatments (CBT) of OCD have dramatically improved the prognosis for the disorder. However, a significant proportion of individuals presenting with OCD may still fail to benefit from treatment. In this paper, we present current CBT treatment models of OCD. We then propose several ways of enhancing CBT for OCD by targeting clients' attachment anxiety and dysfunctional self perceptions.}, } @article {pmid20192588, year = {2009}, author = {Mamoon, N and Hassan, U and Mushtaq, S}, title = {Breast carcinoma in young women aged 30 or less in Northern Pakistan - the Armed Forces Institute of Pathology experience.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {10}, number = {6}, pages = {1079-1082}, pmid = {20192588}, issn = {2476-762X}, mesh = {Adult ; Age Factors ; Age of Onset ; Biopsy ; Breast Neoplasms/*epidemiology/pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Invasiveness ; Neoplasm Staging ; Pakistan/epidemiology ; Prognosis ; Registries ; }, abstract = {OBJECTIVE: The study was carried out to document the occurrence of early onset breast cancer in our population and to assess prognostic variables.

METHODS: Records of a total of 1,644 female patients diagnosed with breast carcinoma during the last four years (Jan 2005 - Dec 2008) at the Histopathology Department, Armed Forces Institute of Pathology (AFIP) were retrieved from the AFIP tumour registry. All cases of breast carcinoma diagnosed in young females, 30 years of age or less, were selected and assessed for the type of specimen, tumour type, size and grade, presence or absence of lymph node metastasis, number of lymph nodes recovered and number of lymph nodes involved. Data were entered into SPSS version 11 to calculate mean, median, mode and standard deviation for quantitative variables and frequencies and percentages for qualitative variables.

RESULTS: The mean age was 28+/-2.7 years and the mean tumour size was 3.7+/-2.9 cm. Most frequent age group was 26-30 years (78.6%). The most common histological tumour type was invasive ductal carcinoma (88.7%), followed by invasive lobular carcinoma (5.4%). Seven out of 168 (4.2%) tumours were less than 2 cm in size, 69(41.1%) were between 2-5 cm and 39 (23.2%) were greater than 5 cm. Grade 2 (57.1%), followed by grade 3 (29.8%) were the most frequent. Out of 68 cases in which lymph nodes were included, lymph node metastasis was seen in 55(80.8%).

CONCLUSION: Breast cancer is much commoner in young women in Pakistan as compared to the rest of the world. It is important to keep this in mind when evaluating even very young females with breast lumps.}, } @article {pmid20192585, year = {2009}, author = {Jamal, S and Mushtaq, H and Mubarik, A and Malik, TM}, title = {Estrogen receptor, progesterone receptor, HER2/neu, P53 and Ki-67 status of male breast carcinomas in Pakistan.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {10}, number = {6}, pages = {1067-1070}, pmid = {20192585}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms, Male/epidemiology/*metabolism/*pathology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Pakistan/epidemiology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {OBJECTIVE: The aim of present study was to assess the status of estrogen and progesterone receptors, HER2/neu, p53 and ki-67 in male breast carcinomas in our institute.

STUDY DESIGN: A descriptive study, carried out in the Department of Pathology (Histopathology), Army Medical College, Rawalpindi, Pakistan from June 2008 to January 2009.

SUBJECTS AND METHODS: In this study 45 cases of male breast carcinoma, including all the histological subtypes were assessed with original pathology reports of each case investigated for the age, laterality of breast, histological type of tumour and tumour grade. Tumour blocks of each case were retrieved for immunohistochemical staining of estrogen and progesterone receptors and HER2/neu, ki-67 and p53 scoring was accomplished using established protocols.

RESULTS: The majority of the cases were above 65 years of age. Histologically, the invasive ductal carcinoma was the predominant lesion. In total 95.5% of the cases were estrogen and progesterone (ER and PR) receptor positive. The HER2/neu staining was positive in 84.4% cases. According to the percentage of nuclear staining, 77.7% of the cases were p53 positive and 35.6% of the cases had strong nuclear staining intensity. A total of 55.5% of the tumours showed proliferation by ki-67.

CONCLUSION: The majority of male breast carcinomas in Pakistan are ER and PR positive and demonstrate immunoreactions for prognostic markers. The results point to a relatively aggressive nature of such lesions in our institute.}, } @article {pmid19116033, year = {2008}, author = {Gur-Dedeoglu, B and Konu, O and Kir, S and Ozturk, AR and Bozkurt, B and Ergul, G and Yulug, IG}, title = {A resampling-based meta-analysis for detection of differential gene expression in breast cancer.}, journal = {BMC cancer}, volume = {8}, number = {}, pages = {396}, pmid = {19116033}, issn = {1471-2407}, mesh = {Breast/metabolism ; Breast Neoplasms/*genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/metabolism ; Carcinoma, Lobular/genetics/metabolism ; Databases, Genetic ; Female ; Gene Expression Regulation, Neoplastic/*genetics ; Humans ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures.

METHODS: A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis.

RESULTS: The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results.

CONCLUSION: The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.}, } @article {pmid19115704, year = {2008}, author = {Aydin, O and Bagci, P and Akyildiz, EU and Ozguroglu, M and Ilvan, S}, title = {Metastasis from breast carcinoma to endometrial polyp.}, journal = {European journal of gynaecological oncology}, volume = {29}, number = {6}, pages = {666-668}, pmid = {19115704}, issn = {0392-2936}, mesh = {Bone Neoplasms/*secondary ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Endometrial Neoplasms/*secondary ; Fatal Outcome ; Female ; Humans ; Middle Aged ; }, abstract = {Metastasis of a breast carcinoma to an endometrial polyp is extremely rare, with only ten cases having been reported in the literature up to now. We present the case of a 60-year-old woman with invasive ductal carcinoma who complained of vaginal bleeding. She underwent hysteroscopy with biopsy. Microscopic examination revealed an endometrial polyp which contained foci of adenocarcinoma. The morphologic features of the tumor were identical to the original breast carcinoma.}, } @article {pmid19112575, year = {2009}, author = {Spiliopoulos, D and Spiliopoulos, M and Dandolu, V and Mastrogiannis, D}, title = {Vulvar and breast Paget's disease with synchronous underlying cancer: a unique association.}, journal = {Archives of gynecology and obstetrics}, volume = {280}, number = {2}, pages = {313-315}, doi = {10.1007/s00404-008-0892-0}, pmid = {19112575}, issn = {1432-0711}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/therapy ; Female ; Humans ; Middle Aged ; *Neoplasm Recurrence, Local ; *Neoplasms, Second Primary ; Paget Disease, Extramammary/*pathology/therapy ; Paget's Disease, Mammary/*pathology/therapy ; Vulvar Neoplasms/*pathology/therapy ; }, abstract = {BACKGROUND: We report a unique case of Paget's disease of vulva and breast. Sequentially the patient had invasive ductal carcinoma of the breast, 5 years later was diagnosed with vulvar Paget's with underlying adenocarcinoma and after another 2 years was diagnosed with Paget's disease of the breast.

CASE: A 58-year-old woman with invasive ductal cancer of the left breast was treated with lumpectomy, lymph node dissection, radiation therapy and tamoxifen. Five years later and after complaints of longstanding vulvar pruritus, the patient was diagnosed with vulvar Paget's disease and treated with simple vulvectomy, which revealed a concurrent underlying adenocarcinoma. Subsequently there was recurrence of vulvar malignancy and wide local excision was performed. Seven years after the initial diagnosis of the breast cancer, a biopsy of a left areolar red, ulcerated lesion revealed Paget's disease of the breast.

CONCLUSION: Physicians need to be cognizant of the rare occurrence of mammary and extramammary Paget's disease with underlying malignancies in both locations. A thorough physical examination including biopsy is essential for early detection and appropriate management.}, } @article {pmid19107615, year = {2008}, author = {Kuroda, N and Fujishima, N and Ohara, M and Hirouchi, T and Mizuno, K and Hayashi, Y and Lee, GH}, title = {Coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast: presentation as separate tumors.}, journal = {Medical molecular morphology}, volume = {41}, number = {4}, pages = {238-242}, pmid = {19107615}, issn = {1860-1480}, mesh = {Adenomyoepithelioma/diagnosis/*pathology/surgery ; Aged ; Antigens, CD34/metabolism ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal/diagnosis/*pathology/surgery ; Female ; Humans ; Japan ; Neoplasms, Second Primary/diagnosis/*pathology/surgery ; }, abstract = {Adenomyoepitheliomas are rare breast tumors. We report an unusual case of adenomyoepithelioma associated with invasive ductal carcinoma here. Histologically, the lesion consisted of two separate tumors. One nodule corresponded to invasive ductal carcinoma consisting of tubular and trabecular arrangements of columnar or cuboidal neoplastic cells. The other tumor corresponded to adenomyoepithelioma consisting of an inner layer of neoplastic cells with basophilic cytoplasm and the outer layer of neoplastic cells with clear cytoplasm. Immunohistochemically, some myofibroblasts were observed in the stroma of both adenomyoepithelioma and invasive ductal carcinoma, but no CD34-positive stromal cells were seen in the stroma of either lesion. The stromal reaction of adenomyoepithelioma resembles that of intraductal papilloma in the previous study. To the best of our knowledge, this is the first case of coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast that were discovered as separate nodules. Clinicians and pathologists should be aware of such an association because they need to distinguish such a case from malignant neoplasms arising in adenomyoepithelioma. Additionally, our preliminary report suggests that the stromal response of adenomyoepithelioma may resemble that of intraductal papilloma.}, } @article {pmid19106577, year = {2008}, author = {Sakurai, K and Enomoto, K and Tani, M and Kitajima, A and Amano, S and Shiono, M}, title = {[Recurrence of skin and lymph nodes from asynchronous breast cancer successfully treated with paclitaxel and toremifene therapy--a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {35}, number = {12}, pages = {2222-2224}, pmid = {19106577}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Mastectomy, Radical ; Middle Aged ; Neoplasm Recurrence, Local/diagnostic imaging/*drug therapy/pathology ; Paclitaxel/*therapeutic use ; Skin Neoplasms/diagnostic imaging/*drug therapy/pathology ; Toremifene/*therapeutic use ; Ultrasonography ; }, abstract = {We report a case of recurrence of skin and lymph nodes from asynchronous breast cancer achieving a significant improvement of QOL by toremifene and paclitaxel therapy. The patient was a 49-year-old woman who received both sides of muscle-preserving radical mastectomy (Bt+Ax: Auchincloss) had a skin redness of her left breast. Aspiration biopsy cytology for the skin led to a diagnosis of Class V. Skin biopsy for the part of the redness was performed. The pathological diagnosis was an invasive ductal carcinoma, negative for estrogen receptor and positive for progesteron receptor, and negative for HER2/neu protein expression. Ultrasonography showed the subpectral and the inflaclavicular lymph nodes swelling and the skin metastasis. Enhancement CT showed no metastasis of brain, lung, liver, and other organs. Although she had already received 6 cycles of tri-weekly FEC (C: 500 mg, E 60 mg, F: 500 mg/m2) after previous operation, we performed 7 cycles of weekly paclitaxel (80 mg/m2) with toremifene (120 mg/day). The response for the lesion of lymph nodes metastasis after paclitaxel and toremifene therapy was evaluated as a complete response. The subpectoral and the inflaclavicular lymph nodes metastasis disappeared. However, the skin redness of her left breast was still remained. She had received a radiation therapy (30 Gy) for skin metastasis. After radiation therapy, we performed a skin biopsy for the part of the redness. The pathological diagnosis was no carcinoma of skin. She had no recurrence during the two years after the treatment. Paclitaxel and toremifene therapy was effective for a recurrent breast tumor and could improve patient's QOL and the clinical outcomes.}, } @article {pmid19106576, year = {2008}, author = {Sakurai, K and Enomoto, K and Tani, M and Kitajima, A and Amano, S and Shiono, M}, title = {[A case of advanced breast cancer successfully treated with paclitaxel and toremifene therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {35}, number = {12}, pages = {2219-2221}, pmid = {19106576}, issn = {0385-0684}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/diagnostic imaging/*drug therapy/*pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Neoplasm Staging ; Paclitaxel/*therapeutic use ; Tomography, X-Ray Computed ; Toremifene/*therapeutic use ; Ultrasonography ; }, abstract = {We report a case of advanced breast cancer with skin ulceration and bleeding (T4bN3bM0: Stage IIIC) achieving a significant improvement of QOL by toremifene and paclitaxel therapy. The patient was a 38-year-old woman with slight anemia who had ulcerative breast lump with skin ulcer. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and progesteron receptor, and negative for HER2/neu protein expression. She received 6 cycles of tri-weekly FEC (C: 500 mg, E: 60 mg, F: 500 mg/m2) and 16 cycles of weekly paclitaxel (80 mg/m2) with toremifene (120 mg/day). The anemia and the bleeding from the tumor disappeared after FEC chemotherapy. The response for breast tumor after paclitaxel and toremifene therapy was evaluated as partial response, and the infraclavicular, subpectoral, and interpectoral lymph nodes metastasis disappeared. Muscle-preserving radical mastectomy (Bt + Ax: Auchincloss) with skin transplantation was performed. She had no recurrence during one year after the operation. Paclitaxel and Toremifene therapy was effective for advanced breast tumor, and can improve a patient QOL and the clinical outcomes in Stage IIIC advanced breast cancer.}, } @article {pmid19102940, year = {2008}, author = {Liu, ZB and Wu, J and Ping, B and Feng, LQ and Shen, ZZ and Shao, ZM}, title = {[Expression of CK5/6 and CK17 and its correlation with prognosis of triple-negative breast cancer patients].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {30}, number = {8}, pages = {610-614}, pmid = {19102940}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Keratin-17/*metabolism ; Keratin-5/*metabolism ; Keratin-6/*metabolism ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Rate ; }, abstract = {OBJECTIVE: To investigate the correlation of CK5/6 and CK17 expression with clinical outcome in patients with triple-negative [ER(-), PR(-), Her-2(-)] breast cancer.

METHODS: 112 patients with breast cancer treated by surgery between 2000 and 2002 were included in this study. All cases were immunohistochemically proven to be triple-negative. Samples of formalin-fixed and paraffin-embedded surgical specimens were obtained for immunohistological examination for CK5/6 and CK17 expression. The correlation of the gene expression with clinicopathological features and outcome of the patients was analyzed.

RESULTS: Of the 112 triple-negative patients, five-year disease-free survival rate was 73.2% (82/112). The positive rate of both CK5/6 and CK17 was 21.4% (24/112), either CK5/6 or CK17 positive was 46.4% (52/112). It was shown by Kaplan-Meier curve that positive CK5/6, CK17 or CKs (CK5/6 or CK17 positive) was correlated with poor five-year disease-free survival (P = 0.020, P = 0.032, P = 0.003); and positive staining of CK5/6 or CKs was correlated with poor five-year overall survival (P = 0.027, P = 0.015). Of the 91 patients with invasive ductal carcinoma, a correlation of CK5/6 or CK17 positive staining with high grade differentiation was observed (P = 0.030), and with axillary lymph node metastasis was also noticed (P = 0.044). Multivariate analysis by Cox regression showed that differentiation grade, pathological stage and expression of CK5/6 were factors affecting both the disease-free-survival and overall-survival, while menopausal status was an independent factor affecting the disease-free-survival.

CONCLUSION: Positive expression of CK5/6 or CK17 in patients with triple-negative breast cancer is correlated with poor prognosis, high grade differentiation and axillary lymph node metastasis.}, } @article {pmid19102215, year = {2008}, author = {Sviteková, M and Minár, L and Pacovský, Z}, title = {[Breast cancer in puerperium].}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {21}, number = {2}, pages = {71-73}, pmid = {19102215}, issn = {0862-495X}, mesh = {Adult ; Breast Neoplasms/*diagnosis/therapy ; Carcinoma, Ductal, Breast/*diagnosis/therapy ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/therapy ; Puerperal Disorders/*diagnosis/therapy ; }, abstract = {AIM: This case study reports an occurence of a mammary gland carcinoma in woman during her pregnancy and puerperium.

CASE REPORT: Patient was 29 years old woman, without any familiar or personal history of cancer or cancer risk factors. There was a finding of palpable resistance in the lateral superior quadrant of right breast in 30 week of gestation, which was considered to be hormonal changes in pregnancy. The third day after delivery a breast ultrasonography was performed because of persisting mastodynia, moderate oedema in described area and resistance nonresponding to the typical finding in period of incipient lactation. The result was suspicious of tumor. The core cut biopsy revealed invasive ductal carcinoma grade 3 and the staging was determinated as T4b N2 M1 (liver). Because of the high clinical stage of the disease, primary sugical therapy (modified radical mastectomy) was not indicated and the patient underwent neoadjuvant chemotherapy followed byradiotherapy. There was a control PET scan after the chemotherapy which confirmed only residual tumor in the area of affected breast and no viable tumor cells in the area of the liver. Additional reduction of the primary tumor lesion occured after the radiotherapy. The control examination 3 months after the treatment found the statement of the relapse of disease. At the present time, 14 months after the delivery, the paliative chemotherapy is planned.

CONCLUSION: Obstetricians should take care not only for routine examinations of pregnant women, but also of the breast changes and when there are uncertain, they must use appropriate diagnostic methods.}, } @article {pmid19101238, year = {2009}, author = {Chen, CA and Hsiao, CH and Wang, JK and Lin, MT and Wu, ET and Chiu, SN and Chiu, HH and Wu, MH}, title = {Implication of QRS prolongation and its relation to mechanical dyssynchrony in idiopathic dilated cardiomyopathy in childhood.}, journal = {The American journal of cardiology}, volume = {103}, number = {1}, pages = {103-109}, doi = {10.1016/j.amjcard.2008.08.044}, pmid = {19101238}, issn = {1879-1913}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*drug therapy/epidemiology/physiopathology ; Cardiotonic Agents/administration & dosage/*therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; *Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Injections, Intravenous ; Male ; Morbidity/trends ; Retrospective Studies ; Risk Factors ; Survival Rate/trends ; Taiwan/epidemiology ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects/physiology ; }, abstract = {We explored the role of QRS prolongation (>or=120 ms) and its relation to mechanical dyssynchrony and outcomes in childhood idiopathic dilated cardiomyopathy (IDC). A total of 89 patients 32.6 ms was used to define intra-LV dyssynchrony. The 1- and 5-year survivals were 70% and 53%, respectively. Requirement of intravenous inotropes at follow-up (hazard ratio 3.10) and initial LV ejection fraction (hazard ratio 0.95) were major prognostic factors. QRS prolongation, primarily left bundle branch block, was identified in 16 patients (18%) and tended to increase the risk of requiring inotropes. Moreover, none of those with QRS prolongation regained normal cardiac function at follow-up. Two patients with QRS prolongation showed marked improvement in cardiac function after cardiac resynchronization therapy. Mechanical dyssynchrony was noted in all patients with QRS prolongation and in 8% (interventricular) or 38% (intra-LV) of those without. In conclusion, QRS prolongation was common in childhood IDC and was possibly associated with persistent LV dysfunction and worse cardiac outcome. Mechanical (inter- and intraventricular) dyssynchrony was highly prevalent in those with QRS prolongation and was still often observed in those without.}, } @article {pmid19099607, year = {2008}, author = {Yu, J and Ohuchida, K and Nakata, K and Mizumoto, K and Cui, L and Fujita, H and Yamaguchi, H and Egami, T and Kitada, H and Tanaka, M}, title = {LIM only 4 is overexpressed in late stage pancreas cancer.}, journal = {Molecular cancer}, volume = {7}, number = {}, pages = {93}, pmid = {19099607}, issn = {1476-4598}, mesh = {AMP-Activated Protein Kinase Kinases ; Adaptor Proteins, Signal Transducing ; Analysis of Variance ; Carcinoma, Pancreatic Ductal/genetics/pathology ; Carcinoma, Papillary/genetics/pathology ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/*genetics ; Humans ; LIM Domain Proteins ; Neoplasm Staging ; Pancreatic Neoplasms/*genetics/pathology ; Protein Serine-Threonine Kinases/genetics ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: LIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, was initially reported to have an oncogenic role in breast cancer. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer.

METHODS: We measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and microdissected target cells (normal ductal cells; pancreatic intraepithelial neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC] cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB] cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTS: 9 of 14 pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples, expression of LMO4 was higher in pancreatic carcinoma than in intraductal papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas (p < 0.0001 for both). We carried out microdissection-based analyses. IDC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B cells (p < 0.001 for both) or PanIN-2 cells (p = 0.014). IPMC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia (p < 0.001), IPMA (p < 0.001) and IPMB cells (p = 0.003).

CONCLUSION: Pancreatic carcinomas (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer.}, } @article {pmid19095813, year = {2009}, author = {Garnett, S and Wallis, M and Morgan, G}, title = {Do screen-detected lobular and ductal carcinoma present with different mammographic features?.}, journal = {The British journal of radiology}, volume = {82}, number = {973}, pages = {20-27}, doi = {10.1259/bjr/52846080}, pmid = {19095813}, issn = {1748-880X}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; False Negative Reactions ; Female ; Humans ; Mammography ; Mass Screening/methods ; Middle Aged ; Observer Variation ; }, abstract = {The aim of this study is to investigate any difference in the shape and location of infiltrating lobular carcinoma (ILC) with respect to the parenchymal density between the cranio-caudal (CC) and medio-lateral oblique (MLO) mammographic views. Six film-readers independently re-read 59 ILC mammograms and a matched sample of 59 infiltrating ductal carcinoma (IDC) mammograms from one 3-year screening round to quantify lesion characteristics. There is fair to moderate reader agreement for parenchymal pattern, lesion shape and location (kappa = 0.41-0.60). Both ILC (33/60, 55%) and IDC (22/65, 37%) appear as a spiculate mass more often on the CC view than on the MLO view. 41% (25/60) of the ILC spiculate masses become architectural distortions or asymmetric densities on the MLO view. No more ILC lesions (4/60, 7%) are seen in dense breasts than IDC (5/65, 8%), but ILC is mainly associated with (58/60, 97%), and rarely isolated from (2/60, 3%), the main glandular density. The appearance of ILC is significantly different between the MLO and CC views (paired Wilcoxon test: z = -17.059; significance level
METHODS: A retrospective review of 91 breast tumors comparing preoperative MRI tumor size to final pathology tumor size was performed.

RESULTS: MRI and pathology tumor size were positively correlated (R = .650), but with an average overestimation by MRI of .63 cm (P <.0001). When stratified by MRI tumor size (< or = 2.0 cm and > 2.0 cm), a significant difference was found only in tumors greater than 2.0 cm (average overestimation = 1.06 cm; P <.0001). This trend continued for the histological subtypes of ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC).

CONCLUSIONS: MRI tumor size correlates with pathology size; however, a significant overestimation exists, particularly for tumors > 2.0 cm. Clinicians should therefore use caution in relying on MRI tumor size in determining candidacy for breast conservation therapy (BCT).}, } @article {pmid19094583, year = {2008}, author = {Cui, LF and Guo, XJ and Wei, J and Liu, FF and Gu, F and Fan, Y and Lang, RG and Fu, L}, title = {[Significance of interleukin-1beta expression and microvascular density in invasive micropapillary carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {9}, pages = {599-603}, pmid = {19094583}, issn = {0529-5807}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma/pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*metabolism ; Female ; Humans ; Interleukin-1beta/*metabolism ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoplasm Invasiveness/*physiopathology ; }, abstract = {OBJECTIVE: To study the significance of interleukin-1beta (IL-1beta) expression and microvascular density (MVD) in invasive micropapillary carcinoma (IMPC) of breast.

METHODS: Immunohistochemical study for IL-1beta and CD34 was performed on 100 cases of IMPC and 97 cases of invasive ductal carcinoma (IDC). The relationship between IL-1beta expression, MVD and various pathologic parameters (estrogen and progesterone receptor status, Ki-67 proliferative index, histologic grade and lymph node metastasis) in IMPC was analyzed.

RESULTS: There was no significant difference in expression of IL-1beta between IMPC and IDC (P = 0.924). The expression of IL-1beta positively correlated with proliferative index (P = 0.023), histologic grade (P = 0.038) and lymph node metastasis (P = 0.008), and negatively correlated with estrogen receptor expression (P = 0.035). The MVD in IMPC was significantly higher than that in IDC (66.4 versus 60.0, P = 0.003). The mean MVD in node-positive IMPC was higher than that in node-negative IMPC (68.8 versus 54.4, P = 0.001). In IMPC, the MVD in histologic grade II and III tumors was much higher than that in histologic grade I tumors (68.3 versus 59.9, P = 0.025). It had no relationship with hormonal receptor status and proliferative index.

CONCLUSION: Overexpression of IL-1beta and high microvessel density may have important roles in tumor cell proliferation and lymph node metastasis in IMPC.}, } @article {pmid19094511, year = {2008}, author = {Ma, CD and Chen, XS and Liu, GY}, title = {[Clinical and pathological characteristics and treatment of elderly patients with breast cancer].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {46}, number = {18}, pages = {1397-1399}, pmid = {19094511}, issn = {0529-5815}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/*therapy ; Female ; Humans ; Retrospective Studies ; }, abstract = {OBJECTIVE: To explore the clinical and pathological characteristics and treatment patterns and the factors influencing treatments of elderly patients with breast cancer.

METHODS: From January 2001 to December 2006, 647 female breast cancer patients over 65 years old were treated. The clinical records were reviewed. All patients were divided into three groups according to age, including 65 to 69 years old group, 70 to 74 years old group and 75 years or elder group. These 647 patients accounted for 13.4% of all breast cancer patients undergoing surgery during the same period. Major pathological type was invasive ductal carcinoma (79.3%). The patients who had chronic comorbid diseases of other systems accounted for 54.7%. Five hundred and eighty-six patients underwent modified radical mastectomy, accounting for 90.6%. Two hundred and thirty-three patients underwent postoperative adjuvant chemotherapy, accounting for 36.0%. The differences of clinicopathological characteristics and treatment patterns between three groups were tested by Chi-square test.

RESULTS: Older patients had more tumors with mucinous and other pathological types, less over-expression of Her2/Neu(+++), higher probability to have comorbidities, higher probability to undergo relatively conservative surgery, lower probability to receive postoperative chemotherapy, and higher probability to receive postoperative endocrine therapy alone.

CONCLUSIONS: Breast cancer in the elderly exhibits distinctive clinical and pathological characteristics. Treatment patterns they received are related to age.}, } @article {pmid19086167, year = {2008}, author = {Wei, G and Kalaitzakis, E and Bergquist, A and Björnsson, E}, title = {Long-term follow-up of patients with acute liver failure of indeterminate aetiology.}, journal = {Scandinavian journal of gastroenterology}, volume = {43}, number = {8}, pages = {984-991}, doi = {10.1080/00365520801965399}, pmid = {19086167}, issn = {0036-5521}, mesh = {Acetaminophen/*adverse effects ; Adult ; Analgesics, Non-Narcotic/adverse effects ; Budd-Chiari Syndrome/*complications ; Disease Progression ; Female ; Follow-Up Studies ; Hepatitis, Viral, Human/*complications ; Humans ; Liver Failure, Acute/diagnosis/*etiology/surgery ; *Liver Transplantation ; Male ; Middle Aged ; Mushroom Poisoning/*complications ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; }, abstract = {OBJECTIVE: To determine the clinical characteristics of patients with acute liver failure of indeterminate cause and their long-term outcome in comparison with patients with acute liver failure of obvious aetiology (acetaminophen and mushroom poisoning, Budd-Chiari syndrome, acute viral hepatitis) and other controls (idiosyncratic drug reactions, autoimmune hepatitis and Wilson's disease).

MATERIAL AND METHODS: All patients with acute liver failure and listed for liver transplantation in Sweden between 1984 and 2006 were included in a retrospective analysis.

RESULTS: A total of 71 patients with acute liver failure were identified, 33 with indeterminate cause (IDC group), 23 with obvious aetiology (OE group) and 15 other controls (OC group). Before admission to the transplant centre, IDC patients were hospitalized in the referring hospital for 9 days (4-15) versus 1.5 days (1-3) in the OE group (p<0.001) and 7 days (2-14) in the OC group (NS). Serum bilirubin was higher (p<0.001), whereas peak creatinine was lower (p=0.001) in the IDC group compared with the OE group but was not significantly different from the OC group. There were no significant differences in 1-, 3-, 5- and 10-year patient and graft survival rates between the IDC group and the OE or the OC group.

CONCLUSIONS: Patients with acute liver failure of indeterminate cause seem to differ from those with obvious aetiology in clinical and biochemical presentation but are similar to other controls. The overall long-term outcome seems to be similar in patients with an unknown aetiology as in those with a specific aetiology.}, } @article {pmid19085710, year = {2008}, author = {Ikeda, Y and Morita, N and Ikeda, T}, title = {Metachronous rectal metastasis from invasive ductal carcinoma of the male breast.}, journal = {Endoscopy}, volume = {40 Suppl 2}, number = {}, pages = {E108-9}, doi = {10.1055/s-2007-995392}, pmid = {19085710}, issn = {1438-8812}, mesh = {Breast Neoplasms, Male/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Humans ; Liver Neoplasms/*secondary ; Male ; Middle Aged ; Rectal Neoplasms/pathology/*secondary ; }, } @article {pmid19083296, year = {2008}, author = {Bonnal, C and Baune, B and Mion, M and Armand-Lefevre, L and L'Heriteau, F and Wolmark, Y and Lucet, JC}, title = {Bacteriuria in a geriatric hospital: impact of an antibiotic improvement program.}, journal = {Journal of the American Medical Directors Association}, volume = {9}, number = {8}, pages = {605-609}, doi = {10.1016/j.jamda.2008.04.004}, pmid = {19083296}, issn = {1538-9375}, mesh = {Aged ; Aged, 80 and over ; Bacteriuria/diagnosis/*drug therapy/urine ; Female ; Geriatric Nursing/*standards ; Hospitals, University ; Humans ; Infection Control ; Male ; Prospective Studies ; Pyelonephritis/diagnosis/drug therapy/urine ; *Quality Assurance, Health Care ; Urinary Tract Infections/diagnosis/drug therapy/urine ; }, abstract = {OBJECTIVES: To prospectively evaluate a management approach to bacteriuria including advice from an infectious diseases consultant (IDC) in geriatric inpatients.

DESIGN: Prospective study from July 1, 2003, to June 30, 2004.

SETTING: A 205-bed geriatric university-affiliated hospital.

PARTICIPANTS: Consecutive hospitalized patients with positive urine cultures.

INTERVENTION: The hospital's infection control department developed recommendations about antimicrobial use for bacteriuria, which were discussed at staff meetings. Treatments for bacteriuria prescribed by ward physicians were reviewed by an IDC, who suggested changes where appropriate. Physicians were free to follow or to disregard the IDC's suggestions.

MEASUREMENTS: Patients with positive urine cultures (UC) were classified as having asymptomatic bacteriuria (AB), urinary tract infection (UTI) or pyelonephritis (PN). Prescribed and actual treatments were compared.

RESULTS: Of 252 consecutive positive UCs in 181 patients, 124 (49%) were classified as AB, 88 (35%) as UTI, and 38 (15%) as PN; 2 cases of prostatitis were excluded. The total number of prescribed antimicrobial days before IDC advice was 729 and the actual number (after IDC advice) was 577, for a 152-day (21%) reduction. Most of the reduction was generated by shortening the treatment duration.

CONCLUSION: Intervention of an IDC resulted in reduced antimicrobial use in older inpatients with bacteriuria.}, } @article {pmid19082617, year = {2009}, author = {Muñoz, M and Fernández-Aceñero, MJ and Martín, S and Schneider, J}, title = {Prognostic significance of molecular classification of breast invasive ductal carcinoma.}, journal = {Archives of gynecology and obstetrics}, volume = {280}, number = {1}, pages = {43-48}, doi = {10.1007/s00404-008-0867-1}, pmid = {19082617}, issn = {1432-0711}, mesh = {Analysis of Variance ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*classification/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*classification/mortality/pathology/therapy ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry/*methods ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/isolation & purification ; Receptors, Progesterone/isolation & purification ; Retrospective Studies ; }, abstract = {OBJECTIVE: Breast carcinoma classification has dramatically changed in recent years following application of molecular techniques. Immunohistochemistry can help select patients for different therapies. The objective of the present report is to determine the prognostic influence of the molecular classification of breast carcinoma with immunohistochemistry.

MATERIALS AND METHODS: We have retrospectively selected a cohort of 257 patients with invasive ductal carcinoma NOS diagnosed and treated in the same hospital between 1997 and 2000. We have classified the cases in four tumor types according to the immunohistochemical expression of several markers, as luminal A tumors [estrogen and/or progesterone receptors (ER/PE) positive and Her-2 negative]; luminal B tumors (ER/PR positive and Her-2 positive); Her-2 positive tumors (ER/PR negative with Her-2 positive); and triple negative phenotype (all markers negative).

RESULTS: In our series, 116 patients had tumors of luminal A type (47.93%); 67 (27.68%) were luminal type B; 33 (13.63%) were Her2 positive; and 26 (10.74%) were triple negative. The recurrence rate was 19% for luminal type A tumors, 25.4% for luminal type B, 39.4% for Her2 positive and 30.8% for triple negative lesions. The mean relapse free survival was 79.07, 73.07, 64.3 and 83,5 months for luminal A and B, Her-2 and triple negative lesions, respectively. Mortality rate reached 11.2% for luminal A tumors compared with 19.4, 33.3 and 26.9% for luminal B, Her2 and triple negative tumors, respectively. The mean overall survival for these groups was 88.42, 81.41, 77.62 and 93.6 months.

CONCLUSION: Molecular classification with immunohistochemistry behaves as a significant prognosticator for breast invasive ductal carcinoma in our series of patients. The worse prognosis observed for Her2 expressing lesions may have changed after trastuzumab use.}, } @article {pmid19080492, year = {2008}, author = {Huang, GL and Zhang, XH and Guo, GL and Huang, KT and Yang, KY and Hu, XQ}, title = {[Expression of microRNA-21 in invasive ductal carcinoma of the breast and its association with phosphatase and tensin homolog deleted from chromosome expression and clinicopathologic features].}, journal = {Zhonghua yi xue za zhi}, volume = {88}, number = {40}, pages = {2833-2837}, pmid = {19080492}, issn = {0376-2491}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Gene Expression ; Humans ; MicroRNAs/*biosynthesis/genetics ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*genetics ; }, abstract = {OBJECTIVE: To investigate the expression of microRNA-21 (mir-21) in invasive ductal carcinoma (IDC) of the breast and its association with phosphatase and tensin homologue deleted from chromosome (PTEN)-10 protein expression and the clinicopathologic features of IDC.

METHODS: Specimens of IDC and normal tissues more than 5 cm away from the tumor tissues were collected from 40 IDC patients, all female, aged 53 (35-77). Stem-loop real-time RT-PCR was used to examine the mir-21 expression. Immunohistochemistry was used to examine the PTEN protein expression in the tumor tissue. The association of mir-21 expression with the PTEN expression and the clinicopathologic features of the breast IDC were analyzed.

RESULTS: Compared with the nontumor control samples, the median (M) of relative expression of mir-21 (2(-DeltadeltaCt)) was 5.770 (25th-75th percentile, 3.605-7.255) in the tumor samples, significantly higher than that of the nontumor control samples (set at 1.000, P<0.001). Reduced PTEN protein expression was seen in 45% (18/22) of all cases. The expression of mir-21 was higher in the group of reduced PTEN expression (with an M of 6.800) than in the group of high PTEN expression (with an M of 4.850, P=0.013). The up-regulated expression of mir-21 was positively correlated with the TNM clinical stage, lymph node positivity, and proliferation index (P=0.021, 0.010, and 0.030 respectively).

CONCLUSION: mir-21 plays an important role in the development and progression of breast cancer. PTEN is possibly one of the targets of mir-21.}, } @article {pmid19080258, year = {2008}, author = {Wang, TT and Frezza, EE and Ma, R and Hu, SY and Liu, CZ and Zhang, GY and Wachtel, MS and Lü, XM and Feng, JB and Lü, CX}, title = {Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities.}, journal = {Chinese medical journal}, volume = {121}, number = {20}, pages = {1969-1974}, pmid = {19080258}, issn = {0366-6999}, mesh = {Acid Anhydride Hydrolases/analysis/*genetics ; Breast/*pathology ; Breast Neoplasms/*genetics ; *Chromosome Fragile Sites ; Female ; *Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins/analysis/*genetics ; Oxidoreductases/analysis/*genetics ; Tumor Suppressor Proteins/analysis/*genetics ; WW Domain-Containing Oxidoreductase ; }, abstract = {BACKGROUND: WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.

METHODS: Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.

RESULTS: Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).

CONCLUSION: Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.}, } @article {pmid19066611, year = {2009}, author = {Millar, EK and Anderson, LR and McNeil, CM and O'Toole, SA and Pinese, M and Crea, P and Morey, AL and Biankin, AV and Henshall, SM and Musgrove, EA and Sutherland, RL and Butt, AJ}, title = {BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {100}, number = {1}, pages = {123-133}, pmid = {19066611}, issn = {1532-1827}, mesh = {Breast Neoplasms/chemistry/*drug therapy/pathology ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/pathology ; Cell Line, Tumor ; DNA-Binding Proteins/analysis/genetics/*physiology ; Estrogen Antagonists/*therapeutic use ; Female ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; RNA, Messenger/analysis ; Receptors, Estrogen/*analysis ; Tamoxifen/*therapeutic use ; Transcription Factors/analysis/genetics/*physiology ; }, abstract = {BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor (ER) function and may influence outcome and response to endocrine therapy in breast cancer. We determined relationships between BAG-1 expression, molecular phenotype, response to tamoxifen therapy and outcome in a cohort of breast cancer patients and its influence on tamoxifen sensitivity in MCF-7 breast cancer cells in vitro. Publically available gene expression data sets were analysed to identify relationships between BAG-1 mRNA expression and patient outcome. BAG-1 protein expression was assessed using immunohistochemistry in 292 patients with invasive ductal carcinoma and correlated with clinicopathological variables, therapeutic response and disease outcome. BAG-1-overexpressing MCF-7 cells were treated with antioestrogens to assess its effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n=189), a high nuclear BAG-1 expression independently predicted improved outcome for local recurrence (P=0.0464), distant metastases (P=0.0435), death from breast cancer (P=0.009, hazards ratio 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n=107; P=0.0191). BAG-1 overexpression in MCF-7 cells augmented antioestrogen-induced growth arrest. A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen.}, } @article {pmid19062233, year = {2009}, author = {Nakash, O and Dargouth, S and Oddo, V and Gao, S and Alegría, M}, title = {Patient initiation of information: exploring its role during the mental health intake visit.}, journal = {Patient education and counseling}, volume = {75}, number = {2}, pages = {220-226}, pmid = {19062233}, issn = {0738-3991}, support = {P50 MH073469-04/MH/NIMH NIH HHS/United States ; P50 MH073469/MH/NIMH NIH HHS/United States ; P60 MD002261/MD/NIMHD NIH HHS/United States ; P60 MD0 02261/MD/NIMHD NIH HHS/United States ; 1P50 MHO 73469//PHS HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Decision Making ; Female ; Humans ; *Interview, Psychological ; Male ; *Mental Disorders/diagnosis/therapy ; Middle Aged ; New England ; *Patient Participation ; Patient Satisfaction ; *Professional-Patient Relations ; Socioeconomic Factors ; }, abstract = {OBJECTIVE: Describe the role of patients' initiation of information in patient-provider communication during mental health intake visits.

METHODS: One hundred and twenty-nine mental health intake visits of diverse racial/ethnic patients were videotaped. Semi-structured interviews were conducted with patients and providers following each intake visit. We qualitatively analyzed the interviews to identify themes related to patients' initiation of information. We quantitatively analyzed the videos of the intake visits utilizing a checklist that identified whether the patient or the provider initiated the information exchanged.

RESULTS: Patient initiation of information affected providers' evaluation of the credence of the information, assessment of rapport and appraisal of the success of the intake visit. Patients' initiation of information varied with patients' race, age and prior treatment experience; and provider's age, discipline and experience. Patients expressed a personal preference either to not be interrupted or to be asked questions by their providers.

CONCLUSION: Our findings illuminate the role of patient initiation of information in provider decision-making and highlight the importance of tailoring the communication style to patients' preferences.

PRACTICE IMPLICATIONS: Encouraging explicit communication with patients about expectations related to information exchange styles is recommended. Improving provider awareness of assumptions regarding their decision-making is also suggested.}, } @article {pmid19060507, year = {2008}, author = {Kafantari, E and Sotiropoulou, M and Sfikakis, P and Dimitrakakis, K and Zagouri, F and Mandrekas, K and Dimopoulos, S and Dimopoulos, MA and Papadimitriou, CA}, title = {Giant cell arteritis of the breast and breast cancer: paraneoplastic manifestation or concomitant disease? A case report.}, journal = {Onkologie}, volume = {31}, number = {12}, pages = {685-688}, doi = {10.1159/000165055}, pmid = {19060507}, issn = {1423-0240}, mesh = {Aged ; Breast/*blood supply ; Breast Neoplasms/*diagnosis ; Diagnosis, Differential ; Female ; Giant Cell Arteritis/*diagnosis ; Humans ; Paraneoplastic Syndromes/*diagnosis ; }, abstract = {BACKGROUND: Giant cell arteritis (GCA) of the breast is one of the less recognized variants of this vasculitis and may represent an isolated finding or a manifestation of a more widespread disease.

CASE REPORT: We present the case of a 74-year-old woman with malaise and a 14-day persistent fever, reaching 38 degrees C. There was a bilateral, painless and mobile axillary lymphadenopathy and a slight tenderness over the medial and lateral upper quadrants of her left breast, as well as an independent palpable tender mass in the upper outer quadrant of the same breast measuring 2 cm in its greatest diameter. Constitutional symptoms, anemia and an elevated erythrocyte sedimentation rate suggestive of polymyalgia rheumatica were also present. An invasive ductal carcinoma of the breast with coincidental pathologic findings of GCA in the same biopsy specimen was revealed. In this case, arteritis was limited to the breast and presented with diffuse breast tenderness. No other artery was involved by GCA. All arteritis-related symptoms disappeared after the removal of the tumor.

CONCLUSIONS: There is a relationship between cancer, particularly breast cancer, and GCA of the same organ, but the real nature of this association still remains unknown.}, } @article {pmid19052036, year = {2009}, author = {Gao, D and Du, J and Cong, L and Liu, Q}, title = {Risk factors for initial lung metastasis from breast invasive ductal carcinoma in stages I-III of operable patients.}, journal = {Japanese journal of clinical oncology}, volume = {39}, number = {2}, pages = {97-104}, doi = {10.1093/jjco/hyn133}, pmid = {19052036}, issn = {1465-3621}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; ErbB Receptors/*analysis ; Female ; Humans ; Lung Neoplasms/*secondary ; Mastectomy, Radical ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate high-risk factors for initial lung metastases from breast invasive ductal carcinomas in operable patients with Stages I-III invasive ductal carcinoma.

METHODS: Data of all patients who underwent radical mastectomy were reviewed retrospectively, and they were confirmed with invasive ductal breast cancer between January 2003 and December 2007. Routine clinical examination data of patients included in the study at primary diagnosis, adjuvant modes and first metastasis sites were recorded. Possible risk factors were easily identified from patients. Twenty-eight potential risk factors were investigated. Finally, 78 patients with complete data in the potential factors were found eligible, and univariate and multivariate analyses were conducted.

RESULTS: Univariate analyses showed that the status of estrogen receptor (ER) and progesterone receptor (PR) and the status of the epidermal growth factor receptor-2 (Her2) were high-risk factors for invasive ductal breast cancer metastasis to the lung as the first organ. P values were, respectively, 0.045, 0.049 and 0.026. Multivariate analyses showed that the pN3 stage needs to be combined with vascular invasion to predict initial lung metastasis. The status of ER and PR was also viewed in combination with p53 negative to predict lung metastasis. Further analyses demonstrated that a subtype of four negative in breast cancer was significantly associated with initial lung metastasis.

CONCLUSIONS: Patients with pN3 stage and vascular invasion were more likely to develop lung metastasis. A new subtype with Her2 negative, both ER-negative and PR negative combination with p53 negative, had a great tendency to develop initial lung metastasis in breast invasive ductal cancer patients.}, } @article {pmid19047898, year = {2009}, author = {Downs-Kelly, E and Nayeemuddin, KM and Albarracin, C and Wu, Y and Hunt, KK and Gilcrease, MZ}, title = {Matrix-producing carcinoma of the breast: an aggressive subtype of metaplastic carcinoma.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {4}, pages = {534-541}, doi = {10.1097/PAS.0b013e31818ab26e}, pmid = {19047898}, issn = {1532-0979}, mesh = {Adenocarcinoma/*secondary/therapy ; Adult ; Aged ; Breast Neoplasms/*pathology/therapy ; Calcinosis ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Chondrogenesis ; Disease-Free Survival ; Extracellular Matrix/*pathology ; Female ; Humans ; Lymph Nodes/pathology ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local ; }, abstract = {Matrix-producing carcinoma (MPC) of the breast is a subtype of metaplastic carcinoma defined as an invasive breast carcinoma with a direct transition of carcinoma to cartilaginous or osseous matrix without an intervening spindle cell component. Our aims were (1) to evaluate specific histologic characteristics of MPC and correlate these with disease recurrence; and (2) to determine whether rates of locoregional and distant recurrence for MPC are significantly different from those of invasive ductal carcinoma. Thirty-two cases of MPC were identified. Fourteen patients (44%) were < or =50 years of age; 10 (31%) had tumors of size < or =2 cm, and 6 (19%) had tumors > or =5 cm. In this series, all tumors contained chondromyxoid or chondroid matrix, and 1 (3.1%) also contained focal (<5%) osseous matrix. High-grade matrix was present in 9 cases (28%), and low-grade matrix was present in 23 (72%). Matrix comprised < or =10% of the tumor in 14 cases (44%), >10% but <40% in 9 (28%), and > or =40% in 9 (28%). The carcinomatous component was high grade in 30 cases (94%), and 19 tumors (59%) had central necrosis. Seven patients (22%) had positive axillary lymph nodes, and 8 (25%) had lymphovascular space invasion (LVSI). LVSI was the only factor independently associated with locoregional recurrence-free survival in multivariate analysis (P=0.043). Although > or =40% matrix was associated with improved distant recurrence-free (DFS) survival in univariate analysis (P=0.044), only LVSI and tumor stage were independently associated with DFS survival in multivariate analysis (P=0.027 and P=0.001, respectively). Compared with matched controls with invasive ductal carcinoma, patients with MPC had decreased locoregional recurrence-free survival (P=0.001) and decreased DRF survival (P=0.001). In summary, MPC is an aggressive subtype of metaplastic carcinoma with a worse clinical outcome than invasive ductal carcinoma.}, } @article {pmid19047897, year = {2009}, author = {Shin, SJ and Simpson, PT and Da Silva, L and Jayanthan, J and Reid, L and Lakhani, SR and Rosen, PP}, title = {Molecular evidence for progression of microglandular adenosis (MGA) to invasive carcinoma.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {4}, pages = {496-504}, doi = {10.1097/PAS.0b013e31818af361}, pmid = {19047897}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma in Situ/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/*pathology ; *Chromosome Aberrations ; Comparative Genomic Hybridization ; DNA, Neoplasm/analysis ; Disease Progression ; Female ; Fibrocystic Breast Disease/chemistry/genetics/*pathology ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Karyotyping ; Microdissection ; Middle Aged ; }, abstract = {Microglandular adenosis (MGA) is an uncommon, benign breast lesion that is characterized by a proliferation of small uniform, round glands lined by a single layer of epithelial cells around open lumina with haphazard infiltrative growth in fibrous and fatty breast tissue. Although MGA usually has an indolent course, there is morphologic evidence that MGA can be a precursor for the development of intraductal and invasive ductal carcinoma. To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization. MGA and carcinomas arising from MGA were typically negative for p63 and positive for S-100 and Ki-67 and occasionally positive for p53. High-resolution comparative genomic hybridization identified recurrent gains and losses in MGA (2q+, 5q-, 8q+, and 14q-) and atypical MGA (1q+, 5q-, 8q+, 14q-, and 15q-). Some examples of MGA and carcinomas arising from MGA harbored few gross chromosomal abnormalities whereas others had considerable genetic instability with widespread aberrations affecting numerous chromosomal arms. Such widespread genetic changes, together with recurrent loss of 5q and gain of 8q were reminiscent of those reported specifically for basal-like, estrogen receptor-negative, and BRCA1-associated breast tumors. Concordant genetic alterations were identified between MGA, atypical MGA, and higher risk lesions (CIS and invasive ductal carcinoma) and in some cases there was an accumulation of genetic alterations as cases "progressed" from MGA to atypical MGA, CIS, and invasive ductal carcinoma. The molecular data suggests that MGA, atypical MGA, and carcinoma arising in MGA in a single case were clonally related. This result implicates MGA as a nonobligate precursor for the development of intraductal and invasive ductal carcinoma.}, } @article {pmid19047097, year = {2008}, author = {Farrell, CJ and Zaupa, C and Barnard, Z and Maley, J and Martuza, RL and Rabkin, SD and Curry, WT}, title = {Combination immunotherapy for tumors via sequential intratumoral injections of oncolytic herpes simplex virus 1 and immature dendritic cells.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {23}, pages = {7711-7716}, pmid = {19047097}, issn = {1078-0432}, support = {R01 NS032677/NS/NINDS NIH HHS/United States ; R01 NS032677-16/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/immunology/therapeutic use ; Combined Modality Therapy ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; Herpesvirus 1, Human/immunology ; Immunohistochemistry ; Immunotherapy/*methods ; Interferon-gamma/biosynthesis ; Mice ; Neoplasms, Experimental/*therapy ; Oncolytic Virotherapy/*methods ; }, abstract = {PURPOSE: Oncolytic herpes simplex virus 1 (oHSV) vectors treat tumors in preclinical models and have been used safely in phase I clinical trials for patients with cancer. Infection of tumors with oHSV also induces specific antitumor immunity. We investigated whether this immunotherapeutic effect is enhanced by combining oHSV infection with intratumoral administration of immature myeloid dendritic cells (iDC).

EXPERIMENTAL DESIGN: Subcutaneous neuroblastoma tumors were established in syngeneic immunocompetent mice and sequentially treated with oHSV(G47Delta) and intratumoral iDCs. Tumor volumes and survival were monitored. Antitumor immune responses were evaluated by immunohistochemistry, IFN-gamma ELISPOT, and CTL assay. Treatment was also evaluated in immunodeficient NOD-SCID mice.

RESULTS: We observed significant reductions in tumor volumes in mice receiving G47Delta + iDCs compared with those treated with G47Delta or iDC monotherapy. Survival was prolonged, with approximately 90% of tumors eradicated in the combination group. Combination therapy led to enhancement of antitumor immune responses, confirmed by increases in IFN-gamma expression by splenocytes harvested from G47Delta + iDC-treated mice. Splenocytes harvested from G47Delta + iDC-treated mice were effective against neuroblastoma tumor cells in a CTL assay. Immunohistochemistry of combination-treated tumors revealed robust lymphocytic infiltrates. Adding iDCs to G47Delta infection in tumors in NOD-SCID mice did not reduce the rate of growth. Substitution of lipopolysaccharide-matured dendritic cells abrogated the enhanced tumor volume reduction seen with combination therapy with iDCs.

CONCLUSIONS: Combination treatment of murine tumors with oHSV and iDCs reduces the volume of established tumors and prolongs survival via enhancement of antitumor immunity.}, } @article {pmid19038525, year = {2009}, author = {Crits-Christoph, P and Gibbons, MB and Ring-Kurtz, S and Gallop, R and Present, J}, title = {A pilot study of community-friendly manual-guided drug counseling.}, journal = {Journal of substance abuse treatment}, volume = {37}, number = {1}, pages = {8-16}, pmid = {19038525}, issn = {1873-6483}, support = {R21 DA016002-03/DA/NIDA NIH HHS/United States ; R21 DA016002/DA/NIDA NIH HHS/United States ; R21-DA016002/DA/NIDA NIH HHS/United States ; R21 DA016002-01/DA/NIDA NIH HHS/United States ; R21 DA016002-02/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Cocaine-Related Disorders/*rehabilitation ; Community Mental Health Services/methods ; Directive Counseling/*methods ; Female ; Follow-Up Studies ; Guideline Adherence ; Humans ; Male ; Manuals as Topic ; Middle Aged ; Pilot Projects ; Professional Competence ; Psychotherapy, Group/*methods ; Treatment Outcome ; }, abstract = {Therapist training manuals that are more "community friendly" are needed to facilitate effectiveness testing and dissemination of treatments to community based setting. The aim of the current project was to create revised versions of individual drug counseling (IDC) and group drug counseling (GDC) treatment manuals for cocaine dependence and to conduct a preliminary study of their effectiveness. After changing the format and context of existing drug counseling manuals to have greater ease of use in the community, draft manuals were given to 23 community-based counselors for their feedback. Final versions were then used in a pilot randomized clinical trial involving 41 cocaine-dependent patients who received 3 months of either IDC + GDC or GDC-alone treatment. Counselors implemented the new treatment manuals with acceptable levels of adherence and competence. Outcome results indicated that substantial change in drug use was evident, but the amount of abstinence obtained was limited.}, } @article {pmid19037993, year = {2009}, author = {Tamaki, K and Moriya, T and Sato, Y and Ishida, T and Maruo, Y and Yoshinaga, K and Ohuchi, N and Sasano, H}, title = {Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis.}, journal = {Cancer science}, volume = {100}, number = {1}, pages = {88-94}, doi = {10.1111/j.1349-7006.2008.01015.x}, pmid = {19037993}, issn = {1349-7006}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/mortality ; Cell Cycle Proteins/analysis/*physiology ; Feedback, Physiological ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/*etiology ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; Vascular Endothelial Growth Factor A/analysis/antagonists & inhibitors ; }, abstract = {Vasohibin-1 is a recently identified negative feedback inhibitor or suppressor of angiogenesis induced by vascular endothelial growth factor (VEGF)-A. The status of vasohibin-1 in human breast carcinoma has not been examined. We examined 151 breast specimens including 98 cases of invasive ductal carcinoma (IDC), 12 of ductal carcinoma in situ (DCIS), 16 of fibroadenoma (FA), six of inflammatory lesion, nine of fibrocystic change and seven of non-pathological breast tissue. We immunolocalized vasohibin-1 and compared its immunoreactivity to that of VEGF-A, basic fibroblastic growth factor (bFGF), VEGF receptor 2 (Flk-1), CD31, CD34 and Ki-67/MIB-1. The correlation of vasohibin-1 immunoreactivity with overall survival (OS), and disease-free survival (DFS) of the patients with breast carcinoma was also evaluated. In addition, we evaluated Ki-67 and CD31, and Ki-67 and vasohibin-1 double-immunostaining for further characterization of neovascularization. Vasohibin-1 was detected in endothelial cells of human breast and its immunodensity was significantly higher in IDC and inflammatory lesions than the other types (P<0.001). In addition, a significant positive correlation was detected between vasohibin-1 and VEGF-A, bFGF or Flk-1 (P<0.001). There was also positive associations between vasohibin-1 and OS (P=0.004) and between vasohibin-1 and DFS (P
MATERIALS AND METHODS: iDC generated with 50 U/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and very immature DC (viDC) generated with 10 U/ml GM-CSF from the bone marrow of Balb/c mice were used for T-cell co-culture.

RESULTS: The measurement of cellular cytotoxicity against the syngeneic murine B-cell leukemia line A20 revealed that T-cells without co-culture or after co-culture with iDC exerted a similar cytotoxicity, whereas T-cells co-incubated with viDC showed a significantly diminished lysis of A20 cells (p<0.05).

CONCLUSION: Antigen-unloaded iDC in contrast to antigen-loaded iDC may not affect antileukemic T-cell cytotoxicity, whereas antigen-unloaded DC cultures generated with a low dose of GM-CSF are able to impair the T-cell-mediated cytolysis of leukemic cells.}, } @article {pmid19032762, year = {2008}, author = {Schobesberger, M and Baltzer, A and Oberli, A and Kappeler, A and Gugger, M and Burger, H and Jaggi, R}, title = {Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores.}, journal = {BMC cancer}, volume = {8}, number = {}, pages = {343}, pmid = {19032762}, issn = {1471-2407}, mesh = {Breast ; Breast Neoplasms/*diagnosis/*genetics/pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/pathology ; Cell Proliferation ; Female ; Genes, erbB-2 ; Genetic Variation ; Humans ; *Oligonucleotide Array Sequence Analysis ; Paraffin Embedding ; Polymerase Chain Reaction ; Prognosis ; RNA, Neoplasm/analysis/isolation & purification ; Receptors, Estrogen/genetics ; }, abstract = {BACKGROUND: Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection.

METHODS: In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR.

RESULTS: Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan(R) Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient.

CONCLUSION: We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen.}, } @article {pmid19031084, year = {2009}, author = {Da Silva, L and Buck, L and Simpson, PT and Reid, L and McCallum, N and Madigan, BJ and Lakhani, SR}, title = {Molecular and morphological analysis of adenoid cystic carcinoma of the breast with synchronous tubular adenosis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {454}, number = {1}, pages = {107-114}, pmid = {19031084}, issn = {0945-6317}, mesh = {Actins/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*complications/genetics/*pathology ; Carcinoma, Adenoid Cystic/*complications/genetics/*pathology ; Cell Proliferation ; DNA, Neoplasm ; Female ; Fibrocystic Breast Disease/*complications/genetics/*pathology ; Genomic Instability/genetics ; Humans ; Keratin-19/metabolism ; Keratin-7/metabolism ; Middle Aged ; S100 Proteins/metabolism ; }, abstract = {Adenoid cystic carcinoma (ACC) of the breast is a rare tumour. Its recognition as a special type of breast carcinoma is very important because its prognosis is better than the not-otherwise-specified invasive ductal carcinoma and its treatment may not include axillary dissection. Tubular adenosis (TA) is a very rare condition of the breast that is histologically benign; however, it has been described in association with invasive ductal carcinoma. There are scant data regarding the molecular genomic alterations in ACC of the breast and no data has been presented on TA. Herein, we provide a morphological characterisation of TA arising synchronically with ACC in the breast. To characterise these lesions, we performed ultrastructural analysis, three-dimensional reconstruction and molecular analysis using immunohistochemistry and comparative genomic hybridisation. The copy number alterations found in ACC were restricted to small deletions on 16p and 17q only, whereas the TA harboured gains on 1q, 5p, 8q, 10q, 11p and 11q and losses on 1p, 10q, 11q, 12q, 14q, 15q and 16q. These molecular data highlight the genomic instability of TA, a benign florid proliferation intermingled with ACC, and do not provide evidence of molecular evolution from TA to ACC.}, } @article {pmid19028509, year = {2009}, author = {Cho, ES and Jang, YJ and Hwang, MK and Kang, NJ and Lee, KW and Lee, HJ}, title = {Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals.}, journal = {Mutation research}, volume = {661}, number = {1-2}, pages = {18-24}, doi = {10.1016/j.mrfmmm.2008.10.021}, pmid = {19028509}, issn = {0027-5107}, mesh = {Animals ; Antioxidants/isolation & purification/pharmacology ; Apoptosis/*drug effects ; Caspase 3/metabolism ; Chlorogenic Acid/isolation & purification/pharmacology ; Coffee/*chemistry ; DNA Fragmentation/drug effects ; Hydrogen Peroxide/toxicity ; JNK Mitogen-Activated Protein Kinases/metabolism ; Neurons/*drug effects/metabolism/*pathology ; Neuroprotective Agents/isolation & purification/*pharmacology ; Oxidative Stress/drug effects ; PC12 Cells ; Phenols/isolation & purification/*pharmacology ; Poly(ADP-ribose) Polymerases/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; bcl-X Protein/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD) are strongly associated with oxidative stress, which is induced by reactive oxygen species (ROS) including hydrogen peroxide (H(2)O(2)). Recent studies suggest that moderate coffee consumption may reduce the risk of neurodegenerative diseases such as AD, but the molecular mechanisms underlying this effect remain to be clarified. In this study, we investigated the protective effects of chlorogenic acid (5-O-caffeoylquinic acid; CGA), a major phenolic phytochemical found in instant decaffeinated coffee (IDC), and IDC against oxidative PC12 neuronal cell death. IDC (1 and 5 microg/ml) or CGA (1 and 5 microM) attenuated H(2)O(2)-induced PC12 cell death. H(2)O(2)-induced nuclear condensation and DNA fragmentation were strongly inhibited by pretreatment with IDC or CGA. Pretreatment with IDC or CGA also inhibited the H(2)O(2)-induced cleavage of poly(ADP-ribose) polymerase (PARP), and downregulation of Bcl-X(L) and caspase-3. The accumulation of intracellular ROS in H(2)O(2)-treated PC12 cells was dose-dependently diminished by IDC or CGA. The activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) by H(2)O(2) in PC12 cells was also inhibited by IDC or CGA. Collectively, these results indicate that IDC and CGA protect PC12 cells from H(2)O(2)-induced apoptosis by blocking the accumulation of intracellular ROS and the activation of MAPKs.}, } @article {pmid19025952, year = {2008}, author = {Kobayashi, M and Kawashima, H and Matsui, O and Zen, Y and Suzuki, M and Inokuchi, M and Noguchi, M and Ohta, T}, title = {Two different types of ring-like enhancement on dynamic MR imaging in breast cancer: correlation with the histopathologic findings.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {28}, number = {6}, pages = {1435-1443}, doi = {10.1002/jmri.21622}, pmid = {19025952}, issn = {1053-1807}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Chi-Square Distribution ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Lymphatic Metastasis ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {PURPOSE: To describe two different types of "ring-like enhancement" seen on dynamic magnetic resonance imaging (MRI) of breast cancer, and compare their histopathological features.

MATERIALS AND METHODS: A total of 326 breast carcinomas in 311 patients were evaluated regarding the existence and appearance of "ring-like enhancement" in comparison to other MR imaging and histopathological findings.

RESULTS: Early peripheral enhancement (EPE) was observed in 81 of 326 lesions (24.8%) and delayed rim enhancement (DRE) in 110 (33.7%). Spiculated mass, invasive ductal carcinoma with abundant stroma, central fibrosis/necrosis, and a higher degree of fat invasion correlated with EPE (P < 0.001). DRE correlated with lobulated or round mass with a smooth border, invasive ductal carcinoma with scanty stroma, higher degrees of inflammatory change and surrounding compressed tissue, and less fat invasion (P <0.001). EPE correlated with the ratio of the peripheral to central blood vessel density (P = 0.0036) and DRE with the ratio of the peritumoral to peripheral lymph vessel density (P = 0.0298).

CONCLUSION: The appearance of two different types of ring-like enhancement on dynamic MRI in breast cancers was affected by the morphologic features, various histological factors reflecting the growth pattern of the mass, and angiogenesis and lymphangiogenesis.}, } @article {pmid19021389, year = {2008}, author = {Majumder, SK and Keller, MD and Boulos, FI and Kelley, MC and Mahadevan-Jansen, A}, title = {Comparison of autofluorescence, diffuse reflectance, and Raman spectroscopy for breast tissue discrimination.}, journal = {Journal of biomedical optics}, volume = {13}, number = {5}, pages = {054009}, doi = {10.1117/1.2975962}, pmid = {19021389}, issn = {1083-3668}, support = {P50 CA098131/CA/NCI NIH HHS/United States ; 5P50 CA098131-03/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/*diagnosis ; Female ; Humans ; Luminescent Measurements/*methods ; Refractometry/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Fluorescence/*methods ; Spectrum Analysis, Raman/*methods ; }, abstract = {For a given diagnostic problem, important considerations are the relative performances of the various optical biopsy techniques. A comparative evaluation of fluorescence, diffuse reflectance, combined fluorescence and diffuse reflectance, and Raman spectroscopy in discriminating different histopathologic categories of human breast tissues is reported. Optical spectra were acquired ex vivo from a total of 74 breast tissue samples belonging to 4 distinct histopathologic categories: invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), fibroadenoma (FA), and normal breast tissue. A probability-based multivariate statistical algorithm capable of direct multiclass classification was developed to analyze the diagnostic content of the spectra measured from the same set of breast tissue sites with these different techniques. The algorithm uses the theory of nonlinear maximum representation and discrimination feature for feature extraction, and the theory of sparse multinomial logistic regression for classification. The results reveal that the performance of Raman spectroscopy is superior to that of all others in classifying the breast tissues into respective histopathologic categories. The best classification accuracy was observed to be approximately 99%, 94%, 98%, and 100% for IDC, DCIS, FA, and normal breast tissues, respectively, on the basis of leave-one-sample-out cross-validation, with an overall accuracy of approximately 99%.}, } @article {pmid19019216, year = {2008}, author = {Stewart, AJ and O'Farrell, DA and Cormack, RA and Hansen, JL and Khan, AJ and Mutyala, S and Devlin, PM}, title = {Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields.}, journal = {Radiation oncology (London, England)}, volume = {3}, number = {}, pages = {39}, pmid = {19019216}, issn = {1748-717X}, mesh = {Brachytherapy/*methods ; Breast/radiation effects ; Breast Neoplasms/*radiotherapy ; Carcinoma, Ductal, Breast/radiotherapy ; Female ; Heart/radiation effects ; Humans ; Lung/radiation effects ; Lymph Nodes/pathology ; Mastectomy ; Prospective Studies ; Radiometry ; Radiotherapy/*methods ; Radiotherapy Dosage ; Tomography, X-Ray Computed/methods ; }, abstract = {PURPOSE: To assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSite applicator and compare to those produced by whole breast external beam radiotherapy (WBRT).

MATERIALS AND METHODS: Dosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400 cGy was 1 cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10 Gy or more (V10) and the dose received by 20 cc of the structure (D20), were calculated as well as the maximum and mean doses received.

RESULTS: Fifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925-1380 cc. Cardiac volumes ranged from 337-551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction.

CONCLUSION: This study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets.}, } @article {pmid19011933, year = {2009}, author = {Ueda, M and Endo, I and Nakashima, M and Minami, Y and Takeda, K and Matsuo, K and Nagano, Y and Tanaka, K and Ichikawa, Y and Togo, S and Kunisaki, C and Shimada, H}, title = {Prognostic factors after resection of pancreatic cancer.}, journal = {World journal of surgery}, volume = {33}, number = {1}, pages = {104-110}, pmid = {19011933}, issn = {0364-2313}, mesh = {Analysis of Variance ; CA-19-9 Antigen/blood ; Carcinoma, Pancreatic Ductal/mortality/pathology/*surgery ; Female ; Humans ; Hypoalbuminemia/mortality ; Japan/epidemiology ; Length of Stay ; Longitudinal Studies ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Pancreaticoduodenectomy/*adverse effects ; Postoperative Period ; Prognosis ; Risk Assessment ; Survival Rate ; }, abstract = {OBJECTIVES: The purpose of this study was to identify important prognostic factors related to the status of a pancreatic tumor, its treatment, and the patient's general condition.

METHODS: Between April 1992 and December 2006, 140 patients underwent a pancreatic resection for invasive ductal carcinoma. Prognostic factors were defined by univariate and multivariate analyses.

RESULTS: The study included 103 tumors in the head of the pancreas and 37 tumors in the body or tail. The median survival time and the actuarial 5-year survival rate for all patients were 14.5 months and 12.3%, respectively. Using the significant prognostic factors identified by univariate analysis, multivariate analysis revealed that a preoperative serum CA19-9 concentration>100 U/ml (HR=1.84, p=0.0074), a tumor size>3 cm (HR=1.74, p=0.0235), venous involvement (HR=2.39, p=0.0006), a transfusion requirement of >or=1000 ml (HR=2.23, p=0.0006), and a serum albumin concentration on 1 postoperative month (1POM)<3 g/dl (HR=2.40, p=0.0009) were significant adverse prognostic factors. The presence of hypoalbuminemia on 1POM significantly correlated with a longer surgical procedure (p=0.0041), extended nerve plexus resection around the superior mesenteric artery (p=0.0456), and a longer postoperative hospital stay (p=0.0063).

CONCLUSION: To improve long-term survival, preserving the patient's general condition by performing a curative resection with a short operation time and minimal blood loss should be the most important principle in the surgical treatment of pancreatic cancer.}, } @article {pmid19010312, year = {2009}, author = {Byrns, MC and Penning, TM}, title = {Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs.}, journal = {Chemico-biological interactions}, volume = {178}, number = {1-3}, pages = {221-227}, pmid = {19010312}, issn = {1872-7786}, support = {R01-CA90744/CA/NCI NIH HHS/United States ; P30 ES013508-03/ES/NIEHS NIH HHS/United States ; T32-DK007314-25/DK/NIDDK NIH HHS/United States ; P30-ES013508/ES/NIEHS NIH HHS/United States ; T32 HD007305/HD/NICHD NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; T32-HD007305-22/HD/NICHD NIH HHS/United States ; T32 DK007314/DK/NIDDK NIH HHS/United States ; R01 CA090744-07/CA/NCI NIH HHS/United States ; R01 CA090744/CA/NCI NIH HHS/United States ; }, mesh = {3-Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism ; Aldo-Keto Reductase Family 1 Member C3 ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Biocatalysis ; Breast Neoplasms/*enzymology ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Enzyme Inhibitors/*pharmacology ; Humans ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/*metabolism ; }, abstract = {Aldo-keto reductase (AKR) 1C3 catalyzes the NADPH-dependent reduction of Delta(4)-androstene-3,17-dione to yield testosterone, reduction of estrone to yield 17beta-estradiol and reduction of progesterone to yield 20alpha-hydroxyprogesterone. In addition, it functions as a prostaglandin (PG) F synthase and reduces PGH(2) to PGF(2)alpha and PGD(2) to 11beta-PGF(2). Immunohistochemistry showed that AKR1C3 is over-expressed in invasive ductal carcinoma of the breast. Retroviral expression of AKR1C3 in MCF-7 breast carcinoma cells shows that each of the assigned reactions occur in a breast cell microenvironment. Steroid and prostaglandin conversions were monitored by radiochromatography. Prostaglandin conversion was validated by a second method using HPLC coupled to APCI-MRM/MS. The combined effect of the AKR1C3 catalyzed 17- and 20-ketosteroid reductions will be to increase the 17beta-estradiol:progesterone ratio in the breast. In addition, formation of PGF(2) epimers would activate F prostanoid receptors and deprive PPARgamma of its putative anti-proliferative PGJ(2) ligands. Thus, AKR1C3 is a source of proliferative signals and a potential therapeutic target for hormone-dependent and -independent breast cancer. Two strategies for AKR1C3 inhibition based on non-steroidal anti-inflammatory drugs were developed. The first strategy uses the Ullmann coupling reaction to generate N-phenylanthranilate derivatives that inhibit AKR1C enzymes without affecting PGH(2) synthase (PGHS) 1 or PGHS-2. The second strategy exploits the selective inhibition of AKR1C3 by indomethacin, which did not inhibit highly related AKR1C1 or AKR1C2. Using known structure-activity relationships for the inhibition of PGHS-1 and PGHS-2 by indole acetic acids we obtained N-(4-chlorobenzoyl)-melatonin as a specific AKR1C3 inhibitor (K(I)=6.0muM) that does not inhibit PGHS-1, PGHS-2, AKR1C1, or AKR1C2. Both strategies are informed by crystal structures of ternary AKR1C3.NADP(+).NSAID complexes. The identification of NSAID analogs as specific inhibitors of AKR1C3 will help validate its role in the proliferation of breast cancer cells.}, } @article {pmid19003444, year = {2007}, author = {Kleinberg, S and Casey, K and Mishra, B}, title = {Systems biology via redescription and ontologies (I): finding phase changes with applications to malaria temporal data.}, journal = {Systems and synthetic biology}, volume = {1}, number = {4}, pages = {197-205}, pmid = {19003444}, issn = {1872-5325}, abstract = {Biological systems are complex and often composed of many subtly interacting components. Furthermore, such systems evolve through time and, as the underlying biology executes its genetic program, the relationships between components change and undergo dynamic reorganization. Characterizing these relationships precisely is a challenging task, but one that must be undertaken if we are to understand these systems in sufficient detail. One set of tools that may prove useful are the formal principles of model building and checking, which could allow the biologist to frame these inherently temporal questions in a sufficiently rigorous framework. In response to these challenges, GOALIE (Gene ontology algorithmic logic and information extractor) was developed and has been successfully employed in the analysis of high throughput biological data (e.g. time-course gene-expression microarray data and neural spike train recordings). The method has applications to a wide variety of temporal data, indeed any data for which there exist ontological descriptions. This paper describes the algorithms behind GOALIE and its use in the study of the Intraerythrocytic Developmental Cycle (IDC) of Plasmodium falciparum, the parasite responsible for a deadly form of chloroquine resistant malaria. We focus in particular on the problem of finding phase changes, times of reorganization of transcriptional control.}, } @article {pmid19003431, year = {2008}, author = {Schmidt, M}, title = {Diffusion of synthetic biology: a challenge to biosafety.}, journal = {Systems and synthetic biology}, volume = {2}, number = {1-2}, pages = {1-6}, pmid = {19003431}, issn = {1872-5325}, abstract = {One of the main aims of synthetic biology is to make biology easier to engineer. Major efforts in synthetic biology are made to develop a toolbox to design biological systems without having to go through a massive research and technology process. With this "de-skilling" agenda, synthetic biology might finally unleash the full potential of biotechnology and spark a wave of innovation, as more and more people have the necessary skills to engineer biology. But this ultimate domestication of biology could easily lead to unprecedented safety challenges that need to be addressed: more and more people outside the traditional biotechnology community will create self-replicating machines (life) for civil and defence applications, "biohackers" will engineer new life forms at their kitchen table; and illicit substances will be produced synthetically and much cheaper. Such a scenario is a messy and dangerous one, and we need to think about appropriate safety standards now.}, } @article {pmid19003430, year = {2008}, author = {Schmidt, M and Torgersen, H and Ganguli-Mitra, A and Kelle, A and Deplazes, A and Biller-Andorno, N}, title = {SYNBIOSAFE e-conference: online community discussion on the societal aspects of synthetic biology.}, journal = {Systems and synthetic biology}, volume = {2}, number = {1-2}, pages = {7-17}, pmid = {19003430}, issn = {1872-5325}, abstract = {As part of the SYNBIOSAFE project, we carried out an open electronic conference (e-conference), with the aim to stimulate an open debate on the societal issues of synthetic biology in a proactive way. The e-conference attracted 124 registered participants from 23 different countries and different professional backgrounds, who wrote 182 contributions in six different categories: (I) Ethics; (II) Safety; (III) Security; (IV) IPR; (V) Governance and regulation; (VI) and Public perception. In this paper we discuss the main arguments brought up during the e-conference and provide our conclusions about how the community thinks, and thinks differently on the societal impact of synthetic biology. Finally we conclude that there is a chance for an open discourse on the societal issues of synthetic biology happening, and that the rules to govern such a discourse might be set up much easier and be respected more readily than many would suggest.}, } @article {pmid19000051, year = {2008}, author = {Geraghty, PR and van den Bosch, MA and Spielman, DM and Hunjan, S and Birdwell, RL and Fong, KJ and Stables, LA and Zakhour, M and Herfkens, RJ and Ikeda, DM}, title = {MRI and (1)H MRS of the breast: presence of a choline peak as malignancy marker is related to K21 value of the tumor in patients with invasive ductal carcinoma.}, journal = {The breast journal}, volume = {14}, number = {6}, pages = {574-580}, pmid = {19000051}, issn = {1524-4741}, support = {P41 RR009784/RR/NCRR NIH HHS/United States ; P41 RR009784-15/RR/NCRR NIH HHS/United States ; R01 CA048269/CA/NCI NIH HHS/United States ; R01 CA048269-12/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*pathology ; Choline/*analysis ; False Negative Reactions ; Female ; Humans ; Image Enhancement ; Magnetic Resonance Imaging/*methods ; Magnetic Resonance Spectroscopy/*methods ; Middle Aged ; Neoplasm Invasiveness ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {To assess which specific morphologic features, enhancement patterns, or pharmacokinetic parameters on breast Magnetic Resonance Imaging (MRI) could predict a false-negative outcome of Proton MR Spectroscopy ((1)H MRS) exam in patients with invasive breast cancer. Sixteen patients with invasive ductal carcinoma of the breast were prospectively included and underwent both, contrast-enhanced breast MRI and (1)H MRS examination of the breast. The MR images were reviewed and the lesions morphologic features, enhancement patterns and pharmacokinetic parameters (k21-value) were scored according to the ACR BI-RADS-MRI lexicon criteria. For the in vivo MRS studies, each spectrum was evaluated for the presence of choline based on consensus reading. Breast MRI and (1)H MRS data were compared to histopathologic findings. In vivo (1)H MRS detected a choline peak in 14/16 (88%) cancers. A false-negative (1)H MRS study occurred in 2/16 (14%) cancer patients. K21 values differed between both groups: the 14 choline positive cancers had k21 values ranging from 0.01 to 0.20/second (mean 0.083/second), whereas the two choline-negative cancers showed k21 values of 0.03 and 0.05/second, respectively (mean 0.040/second). Also enhancement kinetics did differ between both groups; typically both cancers that were choline-negative showed a late phase plateau (100%), whereas this was only shown in 5/14 (36%) of the choline positive cases. There was no difference between both groups with regard to morphologic features on MRI. This study showed that false-negative (1)H MRS examinations do occur in breast cancer patients, and that the presence of a choline peak on (1)H MRS as malignancy marker is related to the k21 value of the invasive tumor being imaged.}, } @article {pmid18998256, year = {2008}, author = {}, title = {Why IDC-10 can't wait.}, journal = {Journal of AHIMA}, volume = {79}, number = {10}, pages = {18, 20}, pmid = {18998256}, issn = {1060-5487}, mesh = {Electronic Data Processing/standards ; Health Insurance Portability and Accountability Act ; Humans ; Insurance Claim Reporting/standards ; International Classification of Diseases/*legislation & jurisprudence ; Medical Records/standards ; Quality Assurance, Health Care ; Time ; United States ; United States Dept. of Health and Human Services ; }, } @article {pmid18997986, year = {2008}, author = {Brooksbank, R and Badenhorst, D and Sliwa, K and Norton, G and Woodiwiss, A}, title = {The G-308A polymorphism of the TNF-alpha gene does not predict changes in cardiac function in response to medical therapy for idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular journal of Africa}, volume = {19}, number = {5}, pages = {254-258}, pmid = {18997986}, issn = {1995-1892}, mesh = {Alleles ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/drug therapy/*genetics/physiopathology ; Cardiotonic Agents ; Cardiovascular Agents/*therapeutic use ; Case-Control Studies ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Female ; Genotype ; Heart Ventricles ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Prospective Studies ; Risk Factors ; Tumor Necrosis Factor-alpha/*genetics ; }, abstract = {The G-308A polymorphism of the tumour necrosis factor-alpha (TNF-alpha) gene, a variant that influences TNF-alpha transcription, may contribute to non-ischaemic dilated cardiomyopathy. To evaluate whether TNF-alpha genotyping may assist in identifying a subset of patients who could potentially benefit from immunomodulatory therapy, we assessed the relationship between the G-308A polymorphism of the TNF-alpha gene and changes in left ventricular (LV) chamber dimensions and systolic function in patients with idiopathic dilated cardiomyopathy (IDC) before and six months after diuretic, digoxin and angiotensin-converting enzyme inhibitor (ACEI) therapy. In 331 patients with IDC and 349 controls, the TNF-2 (A) allele (odds ratio = 1.509, 95% CI = 1.130-2.015, p < 0.01) and the TNF-12/22 (AG/GG) genotype (odds ratio = 1.620, 95% CI = 1.159-2.266, p < 0.01) were associated with IDC. However, in 122 patients with IDC, the TNF-alpha genotype was not associated with plasma TNF-alpha concentrations. In 133 patients with IDC, the TNF-alpha genotype failed to predict either the severity of pump dysfunction and cardiac dilatation at baseline, or changes in pump function and cardiac dimensions after six months of medical treatment. We conclude therefore that although the TNF-alpha gene G-308A polymorphism may contribute to the development of IDC, it does not influence pump function or adverse cardiac remodelling in patients with IDC. Genotyping for this variant is therefore unlikely to assist in identifying patients with heart failure who may be particularly susceptible to novel immunomodulatory therapeutic strategies.}, } @article {pmid18987996, year = {2009}, author = {Kabukcuoglu, F and Kabukcuoglu, Y and Tanik, C and Sakiz, D and Karsidag, S}, title = {Breast carcinoma metastasis in recurrent myxoid liposarcoma.}, journal = {Pathology oncology research : POR}, volume = {15}, number = {3}, pages = {467-471}, pmid = {18987996}, issn = {1532-2807}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Liposarcoma, Myxoid/metabolism/*pathology ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm Staging ; Neoplasms, Second Primary/metabolism/*pathology ; Radiotherapy ; Soft Tissue Neoplasms/metabolism/*pathology ; }, abstract = {Tumor to tumor metastasis is a rare, but well recognized entity, most commonly involving a carcinoma metastasis to a benign or low grade mesenchymal tumor. A case of breast carcinoma metastasis in a recurrent myxoid liposarcoma is presented in this study. A 52-year-old female patient with a history of breast carcinoma (70% invasive lobular carcinoma and 30% invasive ductal carcinoma) presented with a mass in the right lumbar region. The excised mass was diagnosed as myxoid liposarcoma. The tumor recurred twice and was reexcised. Microscopic examination of the second recurrence revealed multiple foci of breast carcinoma metastases in myxoid liposarcoma. Immunohistochemical study showed staining for CK19, GCDFP-15, estrogen and progesterone in metastases. Both breast carcinoma metastasis and myxoid liposarcoma were immunoreactive for E-cadherin and beta-catenin. To our knowledge, this is the first reported case of breast carcinoma metastasis in myxoid liposarcoma, and the first occurrence of metastasis in a liposarcoma.}, } @article {pmid18987550, year = {2009}, author = {Zhang, MQ and Lennerz, JK and Dehner, LP and Brunt, LM and Wang, HL}, title = {Granulomatous inflammatory pseudotumor of the spleen: association with Epstein-Barr virus.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {17}, number = {3}, pages = {259-263}, doi = {10.1097/PAI.0b013e318189f10f}, pmid = {18987550}, issn = {1533-4058}, mesh = {Aged ; Epstein-Barr Virus Infections/complications/*diagnosis/pathology ; Female ; Granuloma/*diagnosis/pathology/virology ; Granuloma, Plasma Cell/*diagnosis/pathology/virology ; Herpesvirus 4, Human/*isolation & purification ; Humans ; RNA, Viral/analysis ; Splenic Diseases/*diagnosis/pathology/virology ; }, abstract = {A 74-year-old woman with a clinical history of invasive ductal carcinoma of the breast was found to have a splenic mass during a routine radiographic survey. Splenectomy revealed a 3-cm well-demarcated lesion, which on histopathologic examination consisted of heterogeneous inflammatory cells. A striking feature of the lesion was the presence of innumerable well-formed non-necrotizing granulomas. Immunohistochemical studies confirmed the lesion to be composed mainly of mixed T and B lymphocytes, histiocytes, and plasma cells. No spindle cell component was evident on light microscopic examination or by immunohistochemical staining for smooth muscle actin, anaplastic lymphoma kinase, or follicular dendritic cell markers CD21 and CD35. Interestingly, Epstein-Barr virus-encoded RNA and latent membrane protein were detected by in situ hybridization and immunohistochemistry in numerous lymphohistiocytic cells within the lesion, but not in surrounding uninvolved splenic tissue. To our knowledge, this case represents a rare example of splenic inflammatory pseudotumor with exuberant granulomatous reaction in association with Epstein-Barr viral infection.}, } @article {pmid18987549, year = {2009}, author = {Acs, G and Paragh, G and Chuang, ST and Laronga, C and Zhang, PJ}, title = {The presence of micropapillary features and retraction artifact in core needle biopsy material predicts lymph node metastasis in breast carcinoma.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {2}, pages = {202-210}, doi = {10.1097/PAS.0b013e318185e171}, pmid = {18987549}, issn = {1532-0979}, mesh = {*Artifacts ; *Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*pathology ; Middle Aged ; Paraffin Embedding ; Tissue Array Analysis ; Tissue Fixation ; }, abstract = {Retraction artifact around tumor cell nests is a characteristic feature of invasive micropapillary carcinoma (IMPC), a special type of breast cancer commonly associated with nodal metastasis. We have recently reported that the extent of retraction artifact in usual invasive ductal carcinomas (IDC) is also a strong predictor of nodal metastasis. We examined whether the presence and extent of micropapillary features and retraction artifact in core needle biopsy of breast cancers can predict nodal metastasis in a prospective series of 47 IMPC and 424 IDC. Micropapillary features were present on core needle biopsy in 28 of 47 IMPC cases. Nodal metastases were found in 21 of 28 and 14 of 19 IMPC cases with and without micropapillary features present on core needle biopsy, respectively. Lymph node metastasis was significantly associated with the presence of micropapillary features, but not with its extent within these tumors. The presence of extensive retraction artifact in core needle biopsy samples of IDC also showed a significant association with nodal metastasis. Our results indicate that the presence of micropapillary features or extensive retraction artifact on core needle biopsy of breast carcinoma can predict nodal metastasis. Our results support the notion that the characteristic clear spaces separating the tumor cells from the stroma in IMPC and IDC of the breast are not a random artifactual phenomenon simply resulting from tissue fixation and processing, but rather they are likely related to altered tumor-stromal interactions, which might have an important role in lymphatic tumor spread.}, } @article {pmid18983606, year = {2008}, author = {Gonzalez, LO and Corte, MD and Vazquez, J and Junquera, S and Sanchez, R and Viña, A and Rodriguez, JC and Lamelas, ML and Vizoso, F}, title = {Study of matrix metalloproteinases and their tissue inhibitors in ductal in situ carcinomas of the breast.}, journal = {Histopathology}, volume = {53}, number = {4}, pages = {403-415}, doi = {10.1111/j.1365-2559.2008.03136.x}, pmid = {18983606}, issn = {1365-2559}, mesh = {Breast Neoplasms/*enzymology/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinases/*metabolism ; Tissue Array Analysis ; Tissue Inhibitor of Metalloproteinases/*metabolism ; }, abstract = {AIMS: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS).

METHODS AND RESULTS: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP-7 and TIMP-1 than pure DCIS, as well as a higher expression rate of MMP-9 and TIMP-3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP-9 and -11 and TIMP-3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP-2, -14 and TIMP-1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS.

CONCLUSIONS: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.}, } @article {pmid18982746, year = {2008}, author = {Mustać, E and Zamolo, G and Petković, M and Dordević, G and Radić, J and Grgurević, E and Batinac, T}, title = {Breast infiltrating ductal carcinoma: analysis of hormone, HER-2 receptors and Ki-67 proliferation marker.}, journal = {Collegium antropologicum}, volume = {32}, number = {3}, pages = {741-746}, pmid = {18982746}, issn = {0350-6134}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*pathology ; Female ; Gene Expression ; Humans ; Ki-67 Antigen/*analysis ; Menopause ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*analysis ; }, abstract = {The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR + subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER +PR +), probably dependent (PD) (ER +PR- or ER-PR +) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p = 0.0235), age of the patients (p = 0.000467), histological grade (p = 0.000003), vascular invasion (p = 0.006), HER-2 status (p = 0.0039) and Ki-67 proliferation rate (p = 0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1 + and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate.}, } @article {pmid18982439, year = {2009}, author = {Nodari, S and Metra, M and Milesi, G and Manerba, A and Cesana, BM and Gheorghiade, M and Dei Cas, L}, title = {The role of n-3 PUFAs in preventing the arrhythmic risk in patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular drugs and therapy}, volume = {23}, number = {1}, pages = {5-15}, doi = {10.1007/s10557-008-6142-7}, pmid = {18982439}, issn = {1573-7241}, mesh = {Aged ; Anti-Arrhythmia Agents/*pharmacology ; Arrhythmias, Cardiac/etiology/*prevention & control ; Cardiomyopathy, Dilated/*complications ; Catecholamines/blood ; Cytokines/blood/drug effects ; Docosahexaenoic Acids/*pharmacology ; Double-Blind Method ; Drug Combinations ; Eicosapentaenoic Acid/*pharmacology ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Heart Rate/drug effects ; Humans ; Male ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: N-3 polyunsaturated fatty acids (n-3 PUFAs) intake is associated with a reduction in sudden cardiac death in patients with ischemic heart disease. Their effects in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDC) are unknown.

METHODS: We compared with placebo the effects of n-3 PUFAs administration in 44 patients with IDC and with frequent or repetitive ventricular arrhythmias at Holter monitoring using a randomized, double-blind design. Arrhythmic risk was assessed by microvolt T-wave analysis (MTWA), signal averaged ECG (SAECG), Holter monitoring, power spectral analysis of heart rate (HR) variability, catecholamine and cytokine plasma levels, at baseline and after 6 months.

RESULTS: At MTWA, 7/12 patients (58%) initially positive became negative after n-3 PUFAs while one patient became positive after placebo (p = 0.019). N-3 PUFAs administration was also associated to normalization of SAECG (11/15 patients, p < 0.0015), decrease in non-sustained ventricular tachycardia (NSVT) episodes (p = 0.0002) and NSVT HR (p = 0.0003), improvement in HR variability and decrease in catecholamine and cytokine plasma levels. The ratio of plasma n-6 PUFAs to n-3 PUFAs decreased from 12.01 to 3.48 after n-3 PUFAs.

CONCLUSIONS: N-3 PUFAs administration is associated with favorable effects on parameters related to arrhythmic risk in patients with idiopathic dilated cardiomyopathy. These results are consistent with antiarrhythmic activity independent from their antiischemic effects.}, } @article {pmid18974135, year = {2008}, author = {Riggins, RB and Lan, JP and Zhu, Y and Klimach, U and Zwart, A and Cavalli, LR and Haddad, BR and Chen, L and Gong, T and Xuan, J and Ethier, SP and Clarke, R}, title = {ERRgamma mediates tamoxifen resistance in novel models of invasive lobular breast cancer.}, journal = {Cancer research}, volume = {68}, number = {21}, pages = {8908-8917}, pmid = {18974135}, issn = {1538-7445}, support = {UL1 TR000101/TR/NCATS NIH HHS/United States ; R01 CA096483/CA/NCI NIH HHS/United States ; 1P30-CA51008-16/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; BC030280/BC/NCI NIH HHS/United States ; R01 CA096483-01A1/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; BC051851/BC/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Blotting, Western ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/*pathology ; *Drug Resistance, Neoplasm ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Humans ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Receptors, Estrogen/*physiology ; Tamoxifen/*analogs & derivatives/pharmacology ; Transcription Factor AP-1/physiology ; }, abstract = {One-third of all estrogen receptor (ER)-positive breast tumors treated with endocrine therapy fail to respond, and the remainder is likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers each year and, whereas the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of ERalpha and increased expression of the estrogen-related receptor gamma (ERRgamma). Knockdown of ERRgamma in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERRgamma blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERRgamma-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERRgamma/AP1 signaling in the development of TAM resistance and suggest that expression of ERRgamma may be a marker of poor TAM response.}, } @article {pmid18972942, year = {2008}, author = {Busch, M and Wall, JR and Koch, SM and Anderson, C}, title = {Addressing the disproportionate representation of children of color: a collaborative community approach.}, journal = {Child welfare}, volume = {87}, number = {2}, pages = {255-278}, pmid = {18972942}, issn = {0009-4021}, mesh = {Black or African American/*statistics & numerical data ; Child ; Child Abuse/*ethnology/statistics & numerical data ; Child Custody/statistics & numerical data ; Child Welfare/*ethnology/statistics & numerical data ; *Cooperative Behavior ; Cross-Sectional Studies ; Data Collection/statistics & numerical data ; Foster Home Care/statistics & numerical data ; Hispanic or Latino/statistics & numerical data ; Humans ; Incidence ; Indiana ; Outcome Assessment, Health Care/statistics & numerical data ; *Prejudice ; Risk Factors ; *Social Welfare ; White People/statistics & numerical data ; }, abstract = {The state of Indiana recommended a committee be formed to address the disproportional representation of black youth in out-of-home placements. In response, the Indiana Disproportionality Committee (IDC) was established. This article presents the development, objectives and future of the IDC. One of the objectives, research, will be offered as an example of the committee's collaborative strategies. The IDC, in partnership with another organization, has begun exploring relationships between ethnicity, risk factors and treatment outcomes. The results of this research effort have examined disproportion and disparity, leading the IDC to identify needs for change within the state. Barriers and successes of the IDC will be shared, so that others can use these efforts to guide their own strategies to reduce disproportionality.}, } @article {pmid18954273, year = {2008}, author = {Amichai-Hamburger, Y and Lamdan, N and Madiel, R and Hayat, T}, title = {Personality characteristics of Wikipedia members.}, journal = {Cyberpsychology & behavior : the impact of the Internet, multimedia and virtual reality on behavior and society}, volume = {11}, number = {6}, pages = {679-681}, doi = {10.1089/cpb.2007.0225}, pmid = {18954273}, issn = {1557-8364}, mesh = {Adult ; Female ; Humans ; *Internet ; Introversion, Psychological ; Male ; Motivation ; *Personality ; *Social Behavior ; Surveys and Questionnaires ; }, abstract = {Wikipedia is an online, free access, volunteer-contributed encyclopedia. This article focuses on the Wikipedians' (Wikipedia users) personality characteristics, studying Wikipedians' conceptions of Real-Me and BFI dimensions. To survey these aspects, we posted links to two online web questionnaires; one was targeted at Wikipedians and the second to non-Wikipedia users. One hundred and thirty-nine subjects participated in the study, of which 69 were active Wikipedia members. It was found that Wikipedia members locate their real me on the Internet more frequently as compared to non-Wikipedia members. Variance analysis revealed significant differences between Wikipedia members and non-Wikipedia members in agreeableness, openness, and conscientiousness, which were lower for the Wikipedia members. An interaction was found between Wikipedia membership and gender: introverted women were more likely to be Wikipedia members as compared with extroverted women. The results of this study are discussed with special emphasis on the understanding of the motivators of Wikipedia members.}, } @article {pmid18949740, year = {2008}, author = {Brankovic-Magic, MV and Jankovic, RN and Dobricic, JD and Borojevic, ND and Magic, ZM and Radulovic, SS}, title = {TP53 mutations in breast cancer: association with ductal histology and early relapse of disease.}, journal = {The International journal of biological markers}, volume = {23}, number = {3}, pages = {147-153}, doi = {10.1177/172460080802300303}, pmid = {18949740}, issn = {0393-6155}, mesh = {Adult ; Aged ; Breast Neoplasms/ethnology/*genetics/*pathology ; Case-Control Studies ; Disease-Free Survival ; Female ; *Genes, p53 ; Humans ; Middle Aged ; *Mutation ; Polymorphism, Single-Stranded Conformational ; Receptors, Steroid/metabolism ; Recurrence ; Serbia ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {PURPOSE: This study aimed to investigate the incidence of core domain TP53 mutations in Serbian breast cancer patients in view of their possible correlation with prognostic parameters, tumor characteristics and clinical disease course.

METHODS: 145 breast cancer patients were included. Data on clinical disease course were available for 100 patients including 30 node-negative and 70 node-positive patients. After surgery, node-positive patients underwent adjuvant chemotherapy, mostly CMF. TP53 mutations were detected by PCR-SSCP.

RESULTS: 31 mutations were found in 27/145 patients including 4/59 node-negative patients and 23/83 node-positive patients (4 double mutations). 26/31 TP53 mutations were found in patients with invasive ductal carcinoma and only 2 in patients with invasive lobular carcinoma. The presence of TP53 mutations was correlated with clinical disease course in premenopausal node-positive patients (n=70). 11/20 patients with TP53 mutations relapsed. Within the first 24 months of follow-up, significantly shorter disease-free intervals were observed in TP53-mutated patients.

CONCLUSIONS: TP53 mutations correlated only with nodal status and ductal histology. The significance of the predominant distribution of TP53 mutations in tumors with a ductal histology for the aggressive behavior of these tumors has yet to be proved, since the favorable biological features of tumors with a lobular histology do not result in a better prognosis. Early relapse in mutated-TP53 carriers may support data on its predictive value with respect to adjuvant CMF.}, } @article {pmid18949414, year = {2008}, author = {Kubota, K and Ogawa, Y and Nishioka, A and Murata, Y and Itoh, S and Hamada, N and Morio, K and Maeda, H and Tanaka, Y}, title = {Radiological imaging features of invasive micropapillary carcinoma of the breast and axillary lymph nodes.}, journal = {Oncology reports}, volume = {20}, number = {5}, pages = {1143-1147}, pmid = {18949414}, issn = {1021-335X}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Papillary/*diagnostic imaging/pathology ; Female ; Humans ; Lymph Nodes/diagnostic imaging/pathology ; Lymphatic Metastasis/*diagnostic imaging/pathology ; *Magnetic Resonance Imaging ; *Mammography ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {Invasive micropapillary carcinoma of the breast is of growing clinical significance. The purpose of this study was to identify the radiological imaging features for this type of breast carcinoma and the axillary lymph nodes. The study population consisted of 30 breast cancer patients (8 invasive micropapillary carcinomas and 22 other types of invasive ductal carcinoma). The breast lesions were evaluated with mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) prior to neoadjuvant chemotherapy. The pathological outcome of the axillary lymph nodes in 27 patients was correlated with the sonographic findings. Only contrast-enhanced MRI showed characteristic findings for invasive micropapillary carcinoma. Although invasive micropapillary carcinoma is commonly irregular in shape (7/8) compared with other types of invasive carcinoma (6/22) (p=0.012, chi(2) test), a careful interpretation of radiological imaging to identify lesion borders helped the complete clearance of cancer cells from 6/8 patients with invasive micropapillary carcinoma in one-time breast conservative surgery. The positive and negative predictive values of sonography in diagnosing axillary lymph node metastases in cases of invasive micropapillary carcinoma were 100 and 50%, respectively. In conclusion, contrast-enhanced MRI reveals the irregular shape of invasive micropapillary carcinoma and helps conservative breast surgery to be performed safely. The pathological analysis of axillary nodes in cases of invasive micropapillary carcinoma may prove to be indispensable due to the relatively low negative predictive value of sonography.}, } @article {pmid18942291, year = {2008}, author = {Al-Joudi, FS and Iskandar, ZA and Rusli, J}, title = {The expression of p53 in invasive ductal carcinoma of the breast: a study in the North-East States of Malaysia.}, journal = {The Medical journal of Malaysia}, volume = {63}, number = {2}, pages = {96-99}, pmid = {18942291}, issn = {0300-5283}, mesh = {Biomarkers/analysis ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; DNA-Binding Proteins/*analysis ; Female ; Humans ; Malaysia/epidemiology ; Middle Aged ; }, abstract = {The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.}, } @article {pmid18936904, year = {2009}, author = {Gao, Y and Niu, Y and Wang, X and Wei, L and Lu, S}, title = {Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {87}, number = {2}, pages = {145-152}, pmid = {18936904}, issn = {1432-1440}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Chromosome Aberrations ; Chromosome Banding/methods ; Comparative Genomic Hybridization/*methods ; Disease Progression ; Gene Dosage ; Humans ; Hyperplasia ; Neoplasm Staging ; }, abstract = {Although a simple linear progression model for breast cancer has already been proposed, its validity still remains controversial. Especially, the genetic and molecular features of breast cancer at different stages during the development and progression, as well as their relationship, have rarely been studied under the same experimental conditions simultaneously. According to these limitations in this research area, the current study applied comparative genomic hybridization technique to investigate genomic changes in 15 cases of breast atypical ductal hyperplasia (ADH), 15 cases of ductal carcinomas in situ (DCIS), and 15 cases of invasive ductal carcinomas (IDC) and the relationship among the genetic changes. Thirty commonly altered regions that were identified included known (gains of 1q,8q, 17q,20q,Xq and losses of 8p,13q,16q,17p,22q) and several uncharacterized (gains of 2q,5p, 10p,12q,16p,18q, etc. and losses of 11p13-pter,11q,14q,Xp, etc). The overall frequency of copy number losses was higher in IDC than that in DCIS (P = 0.013). ADH showed more frequent gain of 17q than that in IDC (P = 0.007), and IDC exhibited a higher frequency for the loss of 22q than that in ADH (P = 0.018). On one hand, several common genomic changes shared by ADH, DCIS, and IDC make a linear relationship for these three lesions possible. On the other hand, the heterogeneity has also showed clonal diversification and different pathways of breast cancer progression. The regions of chromosomal copy number alterations may bring new insights into the strategy for tumor progression blocking and the discovery of new potential targets for breast cancer treatment.}, } @article {pmid18936692, year = {2009}, author = {Subhawong, AP and Subhawong, T and Nassar, H and Kouprina, N and Begum, S and Vang, R and Westra, WH and Argani, P}, title = {Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically.}, journal = {The American journal of surgical pathology}, volume = {33}, number = {2}, pages = {163-175}, pmid = {18936692}, issn = {1532-0979}, support = {P50 CA088843/CA/NCI NIH HHS/United States ; P50 CA088843-06A19005/CA/NCI NIH HHS/United States ; P50 CA 88843/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Squamous Cell/metabolism/pathology ; Cyclin-Dependent Kinase Inhibitor p16/biosynthesis/*genetics ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Middle Aged ; Papillomavirus Infections ; Phenotype ; Retinoblastoma Protein/biosynthesis/*genetics ; Tissue Array Analysis ; Tumor Suppressor Protein p53/biosynthesis/genetics ; }, abstract = {Basal-like carcinomas (BLCs) of the breast share discriminatory morphologic features with poorly differentiated high-risk human papilloma virus (HPV)-related squamous cell carcinomas of the oropharynx, penis, and vulva. Because HPV E7 protein inactivates the retinoblastoma (Rb) protein, diffuse p16 expression is a surrogate marker for these high-risk HPV-related carcinomas. HPV E6 protein also inactivates p53, further compromising the G1-S cell cycle checkpoint. The Rb/p16/p53 immunohistochemical profile of BLC of the breast has not been well characterized. Tissue microarrays containing 71 invasive ductal carcinomas (IDCs) of the breast were immunolabeled for p16, Rb, p53, and Ki-67. The cases included 4 distinct groups of IDCs having surrogate immunohistochemical profiles corresponding to categories defined by gene expression profiling (17 luminal A, 7 luminal B, 14 HER-2+, and 21 BLC), along with 12 unclassifiable triple negative carcinomas (UTNCs). Twenty-five of the 71 IDC were Rb negative/p16 diffuse positive (Rb-/p16+). These included 15 of 21 BLC and 9 of 12 UTNC, but only 1 of 14 HER-2 positive cases and none of the 17 luminal A or 7 luminal B cases (P<0.01, BLC or UTNC vs. others). Six of the Rb-/p16+ IDC also had a significant ductal carcinoma in situ component. The ductal carcinoma in situ in 4 of these 6 cases showed the same Rb-/p16+ phenotype as the associated IDC. BLC and UTNC had the highest Ki-67 indices of the 5 groups, even when matched for grade. The Rb-/p16+ phenotype and the Rb-/p16+/p53 overexpressing phenotype correlated with increased proliferation within the BLC group. In conclusion, BLC and UTNC, but not HER-2, luminal A, or luminal B carcinomas, frequently demonstrate an Rb-/p16+ phenotype, similar to the HPV-related squamous cell carcinomas that BLC resemble morphologically. This subset may represent a more homogenous group than BLC as defined currently.}, } @article {pmid18929044, year = {2008}, author = {Brookes, MJ and Bourke, AG}, title = {Radiological appearances of papillary breast lesions.}, journal = {Clinical radiology}, volume = {63}, number = {11}, pages = {1265-1273}, doi = {10.1016/j.crad.2008.02.012}, pmid = {18929044}, issn = {1365-229X}, mesh = {Breast Neoplasms/*diagnostic imaging/surgery ; Humans ; Magnetic Resonance Imaging ; Mammography ; Papilloma, Intraductal/*diagnostic imaging/surgery ; Ultrasonography, Mammary ; }, abstract = {This review illustrates the varied appearances of benign and malignant papillary breast tumours, as identified by a breast cancer-screening programme. The commonest mammographic appearance of a papillary tumour is as a soft-tissue mass, with calcification present in less than half of cases. When calcification is present the pattern is variable, but clusters of pleomorphic calcification can occur, sometimes resembling the mammographic appearance of invasive ductal carcinoma. Ultrasonography of papillary lesions typically shows a solid, oval, intraductal mass, often associated with duct dilatation. A cystic component is also commonly seen, and lesions may appear hypervascular on colour Doppler ultrasound. Magnetic resonance imaging (MRI) has a high sensitivity, but low specificity for detecting papillary tumours, and is useful in establishing the extent and distribution of lesions in patients with multiple papillomatosis. Despite a benign histology on core biopsy, an argument exists for complete surgical excision of all papillary tumours, as a significant proportion of papillomas will contain foci of atypia or overt malignant change.}, } @article {pmid18928525, year = {2008}, author = {Castro, NP and Osório, CA and Torres, C and Bastos, EP and Mourão-Neto, M and Soares, FA and Brentani, HP and Carraro, DM}, title = {Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {10}, number = {5}, pages = {R87}, pmid = {18928525}, issn = {1465-542X}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/*pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; *Genes, Neoplasm ; Humans ; Microdissection ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Proteins/*biosynthesis/genetics ; Oligonucleotide Array Sequence Analysis ; Protein-Lysine 6-Oxidase/genetics ; RNA, Messenger/biosynthesis/genetics ; RNA, Neoplasm/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfotransferases/genetics ; Time Factors ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma.

METHODS: Forty-one samples were evaluated: four non-neoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test.

RESULTS: Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with co-existing invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS.

CONCLUSIONS: We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent.}, } @article {pmid18852879, year = {2008}, author = {Simhadri, VR and Reiners, KS and Hansen, HP and Topolar, D and Simhadri, VL and Nohroudi, K and Kufer, TA and Engert, A and Pogge von Strandmann, E}, title = {Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function.}, journal = {PloS one}, volume = {3}, number = {10}, pages = {e3377}, pmid = {18852879}, issn = {1932-6203}, mesh = {Cell Line ; Dendritic Cells/*metabolism/ultrastructure ; Exosomes/chemistry/metabolism/*physiology ; Flow Cytometry ; Humans ; Killer Cells, Natural/chemistry/*immunology ; Ligands ; Microscopy, Electron ; Molecular Chaperones ; Natural Cytotoxicity Triggering Receptor 3/*metabolism ; Proteins/*metabolism ; }, abstract = {NKp30, a natural cytotoxicity receptor expressed on NK cells is critically involved in direct cytotoxicity against various tumor cells and directs both maturation and selective killing of dendritic cells. Recently the intracellular protein BAT3, which is involved in DNA damage induced apoptosis, was identified as a ligand for NKp30. However, the mechanisms underlying the exposure of the intracellular ligand BAT3 to surface NKp30 and its role in NK-DC cross talk remained elusive. Electron microscopy and flow cytometry demonstrate that exosomes released from 293T cells and iDCs express BAT3 on the surface and are recognized by NKp30-Ig. Overexpression and depletion of BAT3 in 293T cells directly correlates with the exosomal expression level and the activation of NK cell-mediated cytokine release. Furthermore, the NKp30-mediated NK/DC cross talk resulting either in iDC killing or maturation was BAT3-dependent. Taken together this puts forward a new model for the activation of NK cells through intracellular signals that are released via exosomes from accessory cells. The manipulation of the exosomal regulation may offer a novel strategy to induce tumor immunity or inhibit autoimmune diseases caused by NK cell-activation.}, } @article {pmid18848858, year = {2008}, author = {Brusa, D and Garetto, S and Chiorino, G and Scatolini, M and Migliore, E and Camussi, G and Matera, L}, title = {Post-apoptotic tumors are more palatable to dendritic cells and enhance their antigen cross-presentation activity.}, journal = {Vaccine}, volume = {26}, number = {50}, pages = {6422-6432}, doi = {10.1016/j.vaccine.2008.08.063}, pmid = {18848858}, issn = {0264-410X}, mesh = {Antigen Presentation/*immunology ; Apoptosis/*physiology ; Cell Line, Tumor ; Cross-Priming/*immunology ; Dendritic Cells/cytology/*immunology ; Flow Cytometry ; HMGB1 Protein/genetics/metabolism ; HSP70 Heat-Shock Proteins/genetics/metabolism ; Humans ; Neoplasms/*immunology ; Oligonucleotide Array Sequence Analysis ; Phagocytosis ; T-Lymphocytes/immunology ; }, abstract = {Critical issues for cytotoxic lymphocyte (CTL) cross-priming are (a) the maturation state of dendritic cells (DC), (b) the source of the tumor-associated antigens (TAA) and (c) the context in which they are delivered to DCs. Drug-induced apoptosis has recently been implicated in CTL cross-priming. However, since drug-treatment produces in vivo more tumor cells than the DC default apoptotic clearance program can cope with, they are expected to proceed to secondary necrosis and change their molecular pattern. Here we have addressed this issue on renal carcinoma cells (RCC) by using different apoptotic stimuli. UVC, but not gamma-irradiation or anthracyclins, induced after 4h treatment of the RCC cell line K1 a combination of apoptotic (phosphatydilserine and calreticulin plasma membrane mobilization) and necrotic (membrane incompetence) features. Heat shock protein (Hsp)-70 and chromatin-bound high mobility box 1 HMGB1 protein, typical of necrosis, were released during the further 20h and thus made accessible to co-cultured monocyte-derived immature (i) DC. UVC-treated, secondary necrotic RCC cell lines were cross-presented with higher efficiency by cytokine-matured (m) DC than their early apoptotic (i.e. gamma-irradiated) counterpart. Upstream events such as increased tumor uptake, activation of genes involved in the antigen-processing machinery, and increased expression of costimulatory and maturation molecules were also observed after loading iDC with secondary necrotic, but not apoptotic, tumor cells. These data offer a description of the molecular and immunogenic characteristics of post-apoptotic tumors which can be exploited to increase the efficiency of in vivo and ex vivo TAA delivery to the DC cross-presentation pathway.}, } @article {pmid18843552, year = {1999}, author = {Murayama, Y and Yamamoto, Y and Shimojima, N and Takahara, T and Kikuchi, K and Lida, S and Kondo, Y}, title = {Ti breast cancer associated with Von Recklinghausen's neurofibromatosis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {6}, number = {3}, pages = {227-230}, doi = {10.1007/BF02967173}, pmid = {18843552}, issn = {1340-6868}, abstract = {A rare case of breast cancer associated with von Recklinghausen's neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis.A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skin retraction in October, 1998. The patient had von Recklinghausen's disease (neurofibromatosis type 1). The TNM clinical staging was TlcNOMO. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pTlcNlaMO.Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.}, } @article {pmid18839850, year = {2008}, author = {Thanakit, V and Ruangvejvorachai, P and Sampatanukul, P}, title = {Expression of E-cadherin and syndecan-1 in axillary lymph node metastases of breast cancer with and without extracapsular extension.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {91}, number = {7}, pages = {1087-1092}, pmid = {18839850}, issn = {0125-2208}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/*pathology ; Biomarkers, Tumor ; Breast Neoplasms/*pathology ; Cadherins/*biosynthesis ; Female ; Humans ; Lymph Nodes/*pathology ; Middle Aged ; Pilot Projects ; Prognosis ; Syndecan-1/*biosynthesis ; }, abstract = {BACKGROUND: Extracapsular extension of axillary lymph node (ECE) has significantly increased the risk of locoregional and distant recurrence in breast cancer patients.

OBJECTIVE: Identify markers with high biological aggressiveness since it may serve as a prognostic indicator or adjunct to standard treatment.

MATERIAL AND METHOD: The authors immunostained 115 axillary lymph nodes of invasive ductal carcinoma with syndecan-1 and E-cadherin.

RESULTS: The presented data shows a significantly higher number of positive lymph node (8.48 vs. 4.15; p < 0.0001) and larger primary tumor size (3.53 vs. 2.79; p = 0.0029) in ECE patients. Sixty-one cases had node positive and without evidence of ECE, 54 cases had ECE. Syndecan-1 was found to be of significantly high expression (p = 0.001). There was no significant difference in the expression of E-cadherin during progression into extracapsular area (p = 0.12).

CONCLUSION: E-cadherin displays high expression in nodal breast cancer metastases that may have re-expression and has coordinate function with syndecan-1 while invading to the surrounding fatty tissue. The protein is, therefore, likely to play a role in the invasiveness and aggressiveness.}, } @article {pmid18839307, year = {2009}, author = {Viale, G and Rotmensz, N and Maisonneuve, P and Bottiglieri, L and Montagna, E and Luini, A and Veronesi, P and Intra, M and Torrisi, R and Cardillo, A and Campagnoli, E and Goldhirsch, A and Colleoni, M}, title = {Invasive ductal carcinoma of the breast with the "triple-negative" phenotype: prognostic implications of EGFR immunoreactivity.}, journal = {Breast cancer research and treatment}, volume = {116}, number = {2}, pages = {317-328}, doi = {10.1007/s10549-008-0206-z}, pmid = {18839307}, issn = {1573-7217}, mesh = {Age Factors ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Disease-Free Survival ; ErbB Receptors/*metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mastectomy ; Phenotype ; Prognosis ; Radiotherapy ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sentinel Lymph Node Biopsy ; }, abstract = {Invasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59-94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in >or=50% invasive tumor cells (HR 2.39, 95% CI, 1.32-4.34, P = 0.004 for DFS; HR 2.34, 95% CI, 1.20-4.59 P = 0.01 for OS). Age >or= 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer.}, } @article {pmid18837890, year = {2008}, author = {Faour, I and Al-Salam, S and El-Terifi, H and El Taji, H}, title = {The use of a vacuum-assisted biopsy device (Mammotome) in the early detection of breast cancer in the United Arab Emirates.}, journal = {Annals of the New York Academy of Sciences}, volume = {1138}, number = {}, pages = {108-113}, doi = {10.1196/annals.1414.016}, pmid = {18837890}, issn = {1749-6632}, mesh = {Adult ; Aged ; Biopsy, Needle/*methods ; Breast Neoplasms/*diagnosis/pathology ; *Early Diagnosis ; Female ; Humans ; Middle Aged ; United Arab Emirates ; Vacuum ; }, abstract = {Stereotactic core needle biopsy has proven to be an accurate technique for evaluation of mammographically detected microcalcification. The development of the Mammotome biopsy system has led many medical centers to use this vacuum-assisted device for the sampling of microcalcifications in mammographically detected nonpalpable breast lesions. Ninety-six women underwent 101 stereotactic Mammotome core biopsies for mammographic calcifications over a 32-month period in the Department of Surgery at Tawam Hospital, the national referral oncology center in the UAE. The stereotactic procedure was performed by surgeons using the Mammotome biopsy system. Microcalcifications were evident on specimen radiographs and microscopic sections in 96% and 87% of the cases, respectively. Excisional biopsy was recommended for diagnoses of atypical ductal hyperplasia or carcinoma. Patients with benign diagnoses underwent mammographic follow-up. Eighty-one lesions were benign, 5 atypical ductal hyperplasias and 14 carcinomas were diagnosed (2 invasive lobular carcinoma, 4 invasive ductal carcinoma, and 8 intraductal carcinomas in situ: 1 comedo, 1 cribriform, 6 mixed cribriform and micropapillary). Surgical excision in four patients with atypia on Mammotome biopsy (one was lost to follow-up) showed atypical ductal hyperplasia. Surgical excision in seven patients diagnosed with intraductal carcinoma in situ (one patient lost to follow-up) showed intraductal carcinoma with no evidence of microinvasion. Similar diagnoses were made in all the invasive ductal and lobular carcinomas in both Mammotome and excisional biopsies. A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was negligible for microcalcification diagnosed as intraductal carcinoma in situ on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling, diagnosis, and early detection of breast cancer.}, } @article {pmid18837432, year = {2009}, author = {Kabay, SC and Kabay, S and Yucel, M and Ozden, H}, title = {Acute urodynamic effects of percutaneous posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with Parkinson's disease.}, journal = {Neurourology and urodynamics}, volume = {28}, number = {1}, pages = {62-67}, doi = {10.1002/nau.20593}, pmid = {18837432}, issn = {1520-6777}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscle Contraction ; Parkinson Disease/*complications/physiopathology/therapy ; *Tibial Nerve ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder/innervation/*physiopathology ; Urinary Bladder, Neurogenic/etiology/physiopathology/*therapy ; Urinary Bladder, Overactive/etiology/physiopathology/*therapy ; *Urodynamics ; }, abstract = {AIMS: Lower urinary tract dysfunction is often occurs in patients with Parkinson's disease (PD), that is primarily induced by neurogenic detrusor overactivity (NDO) and negatively effect the quality of the patient's life. The aim of this study is to evaluate the acute effects of posterior tibial nerve stimulation (PTNS) on the urodynamic findings in the PD patients with NDO.

METHODS: Thirty-two patients with PD (19 [59.3%] men and 13 [40.6%] women) with NDO were included in the study. Mean age of the patients was 64.2 +/- 8.7 years (range 44-78). Urodynamic studies before and during PTNS were performed. Electrical stimulation was applied unilaterally from the medial malleolus and posterior to the edge of the tibia by using charge-compensated 200 microsec pulses with a pulse rate of 20 Hz. Mean first involuntary detrusor (1st IDCV) contractions and means maximum cystometric capacity (MCC) before and during PTNS was compared.

RESULTS: Mean 1st IDCV on standard cystometry was 145.2 +/- 41.1 (55-265) ml, while it was 244.7 +/- 51.7 (145-390) ml during PTNS. MCC on standard cystometry was 204.8 +/- 40.5 (115-320) ml, while it was 301.2 +/- 51.5 (230-395) ml during stimulation. Mean 1st IDC and mean MCC were significantly improved during PTNS.

CONCLUSIONS: These results have demonstrated the objective acute effect of PTNS on urodynamic parameters. PTNS is acutely effective to suppress detrusor overactivity in PD patients.}, } @article {pmid18836815, year = {2008}, author = {Bagnera, S and Campanino, P and Barisone, F and Mariscotti, G and Gandini, G}, title = {Imaging, histology and hormonal features of five cases of male breast cancer observed in a single year: comparison with the literature.}, journal = {La Radiologia medica}, volume = {113}, number = {8}, pages = {1096-1109}, pmid = {18836815}, issn = {0033-8362}, mesh = {Aged ; Breast Neoplasms, Male/blood/*diagnosis ; Hormones/blood ; Humans ; Male ; Mammography ; Middle Aged ; Time Factors ; Ultrasonography, Doppler, Color ; }, abstract = {PURPOSE: The authors assessed mammographic and ultrasound (US) features and histological and biological characteristics of male breast carcinomas observed in five men (mean age 57.8 years) in a single year and compared the findings with the literature.

MATERIALS AND METHODS: All patients underwent history taking and bilateral mammography and US examination extended to the axillary region and complemented with colour Doppler US.

RESULTS: Three out of five patients had a family history of breast cancer, and all of them had an altered energy balance (mean body mass index 30.8). All subjects had a palpable mass, which was associated with bloody nipple discharge in two cases. Mammography identified all lesions as opacities with irregular margins (mean size 1.98 cm); in one case, it also revealed a nonpalpable contralateral lesion. US demonstrated the presence of inhomogeneously hypoechoic nodules with irregular margins and centrifugal vascular spots in 4/6 lesions. Histology diagnosed invasive ductal cancer (IDC) in 5/6 lesions (83.3%) and ductal carcinoma in situ (DCIS) in the contralateral lesion only.

CONCLUSIONS: The presence of symptoms warrants mammography, which is an accurate method for identifying male breast cancer. The frequency of invasive disease observed in our study was consistent with the literature (80%-90% IDC). The hormonal alterations induced by excess fat in our series appear to be correlated with the development of carcinomas with positive receptor status for both oestrogen and progesterone.}, } @article {pmid18828272, year = {2008}, author = {Yagmurdur, MC and Atac, FB and Tutar, NU and Verdi, H and Isiklar, I and Ozdemir, BH and Ozbek, N and Karakayali, H and Haberal, M}, title = {Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.}, journal = {International surgery}, volume = {93}, number = {3}, pages = {163-168}, pmid = {18828272}, issn = {0020-8868}, mesh = {Alleles ; Breast Neoplasms/*genetics/surgery ; Carcinoma, Ductal, Breast/*genetics/surgery ; Disease-Free Survival ; Female ; Genotype ; Humans ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics ; Plasminogen Activator Inhibitor 1/*genetics ; *Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; Statistics, Nonparametric ; Turkey ; }, abstract = {The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.}, } @article {pmid18826393, year = {2008}, author = {Qadura, M and Othman, M and Waters, B and Chegeni, R and Walker, K and Labelle, A and Ozelo, M and Hough, C and Lillicrap, D}, title = {Reduction of the immune response to factor VIII mediated through tolerogenic factor VIII presentation by immature dendritic cells.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {6}, number = {12}, pages = {2095-2104}, doi = {10.1111/j.1538-7836.2008.03165.x}, pmid = {18826393}, issn = {1538-7836}, mesh = {Animals ; *Antigen Presentation ; Dendritic Cells/*immunology/transplantation ; Dogs ; Factor VIII/*immunology ; Hemophilia A/*immunology ; Immune System Phenomena ; *Immune Tolerance ; Interleukin-10 ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta ; Treatment Outcome ; }, abstract = {BACKGROUND: The development of neutralizing antibodies to factor FVIII (FVIII) represents the most serious complication in the treatment of hemophilia A.

OBJECTIVE: We have explored the potential of using immature dendritic cells (iDCs) to present FVIII in a tolerogenic manner to T cells.

METHODS: The iDCs were isolated from hemophilic murine bone marrow and pulsed with canine cFVIII (cFVIII-iDCs) in the presence or absence of the NFkappaB pathway blocking compound Andrographolide (Andro-cFVIII-iDCs). Three weekly intravenous infusions of one million cFVIII pulsed-iDCs were administered to a group of five hemophilic Balb/c mice. Anti-FVIII antibody levels were monitored by functional Bethesda assay after four weekly intravenous challenges with 2 IU of cFVIII.

RESULTS: We have shown that cFVIII in the presence or absence of Andro is efficiently taken up by iDCs and that this process does not result in the maturation of DCs or the activation of co-cultured T cells. Following repeated infusion of the cFVIII-iDCs and Andro-cFVIII-iDCs into hemophilic mice, which were subsequently challenged with cFVIII, long-term reductions of FVIII inhibitors of 25% and 40%, respectively, were documented. Studies of cytokine release and T-cell phenotypes indicate that the mechanisms responsible for reducing immunologic responsiveness to cFVIII appear to involve an expansion of Foxp3 T regulatory cells in the case of cFVIII-iDC infusion and the elaboration of the immunosuppressive cytokines IL-10 and TGF-beta following andrographolide-treated cFVIII-iDCs.

CONCLUSIONS: This study shows that tolerogenic presentation of cFVIII to the immune system can significantly reduce immunogenicity of the protein.}, } @article {pmid19999196, year = {2008}, author = {Naeem, M and Khan, N and Aman, Z and Nasir, A and Samad, A and Khattak, A}, title = {Pattern of breast cancer: experience at Lady Reading Hospital, Peshawar.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {20}, number = {4}, pages = {22-25}, pmid = {19999196}, issn = {1025-9589}, mesh = {Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Female ; Hospitals, Teaching/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Breast Cancer is the commonest malignancy of females all over the world and second leading cause of death due to cancer among females. The aim of this Descriptive study was to see the various features of breast cancer in order to know the pattern of disease in the recent time. The study was conducted from Jan. 2007 to Dec. 2007 in Surgical C Unit, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan.

METHODS: Study included all patients presenting to and admitted in Surgical C Unit LRH, with carcinoma of breast during the above mentioned period. Name, age, sex, other relevant data, history and examination findings and results of histopathology and other investigations were recorded.

RESULTS: Total of 46 patients was included in the study, out of which there were 46 female and 1 male patients. Most common age group was 40-49 years with 14 patients, followed by 50-59 years with 12 patients. Most common type of carcinoma was infiltrating ductal carcinoma with no specific features with 38 patients. Other types included 2 infiltrating ductal carcinomas of papillary type, 1 mucinous type and 1 medullary type; 3 invasive lobular carcinomas, and 1 mixed lobular and ductal carcinoma. The disease was left sided in 24 cases, right sided in 20 cases while it was bilateral in 2 cases. Upper outer quadrant of the breast was most commonly involved (n = 26). There were 2 cases of stage I, 16 stage II, 20 stage III and 08 cases of stage IV disease. There were 2 cases of grade I, 16 grade II, and 28 cases of grade III.

CONCLUSION: Carcinoma breast is still a common problem presenting at a young to middle age group with invasive ductal carcinoma being the commonest variant with a high grade and a late stage of presentation due to lack of screening and awareness programs.}, } @article {pmid18818987, year = {2009}, author = {Akashi-Tanaka, S and Shien, T and Tsukagoshi, S and Funabasama, S and Miyagawa, K and Terada, K and Yoshida, M and Hojo, T and Kinoshita, T and Moriyama, N}, title = {Whole-breast volume perfusion images using 256-row multislice computed tomography: visualization of lesions with ductal spread.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {1}, pages = {62-67}, doi = {10.1007/s12282-008-0076-6}, pmid = {18818987}, issn = {1880-4233}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*pathology ; Carcinoma in Situ/blood supply/pathology ; Carcinoma, Ductal, Breast/blood supply/pathology ; Contrast Media ; Female ; Humans ; Iohexol ; Middle Aged ; Neovascularization, Pathologic/*diagnostic imaging ; Pilot Projects ; *Radiographic Image Interpretation, Computer-Assisted/methods ; Tomography, X-Ray Computed/*methods ; }, abstract = {BACKGROUND: The aim of this study was to apply perfusion techniques to breast tumors using a prototype 256-row multislice computed tomography (CT) scanner (which allows a wide range of 128 mm to be scanned and can provide whole-breast perfusion maps without any dead angles) to improve contrast and assess the possibility of precisely depicting the extent of breast cancer.

PATIENTS AND METHODS: The study group included seven patients with breast cancer who were scheduled to undergo radical surgery and radiotherapy. Dynamic scanning was performed using a 256-row multislice CT scanner during normal respiration. Volume perfusion images of the entire breast were obtained using the maximum slope method. Perfusion map images and early-phase breast CT images at 54 s were compared by means of pathological examination.

RESULTS: All breast cancers could be distinguished from normal mammary glands based on the perfusion value. The extent of cancer depicted in perfusion images showed excellent agreement with the pathology findings for invasive ductal carcinoma and ductal carcinoma in situ. In three patients, all ductal spread, parts of which were not visualized by early-phase CT, were depicted in volume perfusion images. Simulation analysis suggested that perfusion maps could be generated with fewer scanning points.

CONCLUSION: The results of the present study suggest that volume perfusion imaging may be useful for depicting the extent of breast cancer, with excellent sensitivity. Further research is needed to determine the clinical relevance of these findings.}, } @article {pmid18814924, year = {2009}, author = {Branca, S and Bennati, E and Ferlito, L and Spallina, G and Cardillo, E and Malaguarnera, M and Motta, M and , }, title = {The health-care in the extreme longevity.}, journal = {Archives of gerontology and geriatrics}, volume = {49}, number = {1}, pages = {32-34}, doi = {10.1016/j.archger.2008.04.012}, pmid = {18814924}, issn = {1872-6976}, mesh = {Aged, 80 and over ; Female ; Health Services Needs and Demand ; Health Services for the Aged/*organization & administration ; Hospices ; Humans ; *Longevity ; Male ; }, abstract = {The increase in life expectancy, the decrease of birth rate, and of the death rate in advanced ages caused, particularly in the industrialized countries, a progressive demographic transformation of the society, characterized by an increased proportion of the elderly. We assist an inevitable increase of morbidity and disability, not only due to the global aging of the population, but mainly to the increase of the age class above 80 years. For this reason, it is necessary to create and/or effort, especially in the Western countries, an adequate health-caring network. This should integrate and interact between the hospitals and the territories, offering all sanitary services (e.g., assisted sanitary residences, day hospitals (DHs), hospices, Alzheimer centers, diurnal centers, integrated domiciliary care (IDC), general practitioners), required by the elderly, and particularly by the oldest old people. All this should be maintained by an adequate financial support of the social-economic sources, which are necessary not only to activate the health-care services, but also to favor the economic and fiscal stimulation toward the families maintaining the elderly patients.}, } @article {pmid18813844, year = {2008}, author = {Liu, ZB and Liu, GY and Yang, WT and Di, GH and Lu, JS and Shen, KW and Shen, ZZ and Shao, ZM and Wu, J}, title = {Triple-negative breast cancer types exhibit a distinct poor clinical characteristic in lymph node-negative Chinese patients.}, journal = {Oncology reports}, volume = {20}, number = {4}, pages = {987-994}, pmid = {18813844}, issn = {1021-335X}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/drug therapy/*mortality ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Phenobarbital/analysis ; Prognosis ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; Survival Rate ; }, abstract = {Comparative studies on the clinical features and outcomes of triple-negative subgroups to human epidermal growth factor receptor-2 (HER-2) overexpression, and luminal A and B subgroups in lymph node-negative breast cancer patients, are important to correctly evaluate clinical prognosis. A total of 1132 Chinese breast cancer patients were enrolled in a retrospective analysis. We characterized and identified prognostic information in the triple-negative subgroup [estrogen receptor (ER)-, progesterone receptor (PR)- and HER-2-negative] and compared that to HER-2 overexpression, and the luminal A and B subgroups. By using immunohistochemical staining, the triple-negative subgroup showed 17% (193/1132) in the whole group. However, HER-2 overexpression, and the luminal A and B subgroups were 11.2, 47.9 and 23.9%, respectively. Tumors in the triple-negative subgroup showed a higher histological grade (P=0.025) and lower invasive ductal carcinoma (P=0.007), compared to the three subgroups. More patients in the luminal A subgroup had received adjuvant chemotherapy (P=0.007). The difference of disease-free survival rates among the four subgroups was significant (P=0.0001). The P-value for overall survival was 0.0598. No significant difference among the four subgroups in lymph node-positive and non-chemotherapy breast cancers was found. From our data the poor clinical outcomes were independent of age, histological grade, tumor size, lymph nodal status, chemotherapy and clinical stages. Our data suggest that the triple-negative subgroup exhibits a distinct poor clinical outcome, especially in lymph node-negative Chinese breast cancer patients.}, } @article {pmid18813127, year = {2009}, author = {Chadwick, B and Willmore-Payne, C and Tripp, S and Layfield, LJ and Hirschowitz, S and Holden, J}, title = {Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {17}, number = {1}, pages = {31-39}, doi = {10.1097/PAI.0b013e31817c02c6}, pmid = {18813127}, issn = {1533-4058}, mesh = {Biomarkers, Tumor/*analysis ; Carcinoma, Pancreatic Ductal/diagnosis/etiology/genetics/*pathology ; Classification ; Epithelial Cells/chemistry/pathology ; Epithelium/chemistry/*pathology ; Gene Expression Profiling ; Genes, Neoplasm ; Humans ; Immunohistochemistry ; Intestinal Neoplasms/pathology ; Mucins/chemistry ; Mutation ; Neoplasm Proteins/analysis ; }, abstract = {BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas account for approximately 5% of pancreatic neoplasms. Prognosis is superior to that of pancreatic invasive ductal carcinoma. IPMNs reveal a variety of epithelial linings expressing different mucin staining patterns and may progress along different oncogenic pathways.

MATERIALS AND METHODS: Fifty-two IPMNs were studied for expression of MUC1, MUC2, p16, p21, HER2, cyclin D1, and p53 protein and for mutations in K-ras, HER2, p53, EGFR, and BRAF genes. The cases were evaluated for dysplasia, presence of invasion, and morphology of lining epithelium.

RESULTS: Twenty-six IPMNs appeared intestinal (IN). Five were low, 12 moderate, and 9 high grade. K-ras mutations were found in 15, EGFR mutations in 2, and BRAF mutation in 1. Seven cases were pancreaticobiliary (PB) and all showed moderate to high-grade dysplasia. Six K-ras mutations and 2 p53 mutations were found in PB tumors. p53 mutations were in cases with high-grade dysplasia. Nineteen IPMNs demonstrated a gastric foveolar (GF) pattern. The majority of GF cases had low or moderate dysplasia. Sixteen revealed K-ras mutations and 1 case each demonstrated a HER2 or p53 mutation. Five IPMNs revealed invasive adenocarcinoma, including a colloid carcinoma from an IN type epithelium.

CONCLUSIONS: IN pattern IPMNs were the most common. Mixed histology was common. K-ras mutations were most common, but did not correlate with dysplasia. p53 mutations were seen in 6% of cases (only in GF and PB subtypes). A HER2 mutation was found in a GF IPMN. EGFR and BRAF mutations were restricted to IN IPMNs. These findings suggest the possibility of alternate pathways for carcinogenesis between epithelial subtypes of IPMNs.}, } @article {pmid18807269, year = {2009}, author = {Pengel, KE and Loo, CE and Teertstra, HJ and Muller, SH and Wesseling, J and Peterse, JL and Bartelink, H and Rutgers, EJ and Gilhuijs, KG}, title = {The impact of preoperative MRI on breast-conserving surgery of invasive cancer: a comparative cohort study.}, journal = {Breast cancer research and treatment}, volume = {116}, number = {1}, pages = {161-169}, doi = {10.1007/s10549-008-0182-3}, pmid = {18807269}, issn = {1573-7217}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/*surgery ; Cohort Studies ; Female ; Humans ; *Magnetic Resonance Imaging ; *Mastectomy, Segmental ; Middle Aged ; Preoperative Care/*methods ; Treatment Outcome ; }, abstract = {AIM: To assess whether preoperative contrast-enhanced magnetic resonance imaging (MRI) of the breast influences the rate of incomplete tumor excision.

METHODS: In a cohort of 349 women with invasive breast cancer, patients eligible for breast-conserving therapy (BCT) on the basis of conventional imaging and palpation only (N = 176) were compared to those who had an additional preoperative MRI (N = 173). Multivariate analysis was applied to explore associations with incomplete tumor excision.

RESULTS: MRI detected larger extent of breast cancer in 19 women (11.0%), leading to treatment change: mastectomy (8.7%) or wider excision (2.3%). Tumor excision was incomplete in 22/159 (13.8%) wide local excisions in the MRI group and in 35/180 (19.4%) in the non-MRI group (P = 0.17). Stratified to tumor type, incompletely excised infiltrating ductal carcinoma (IDC) was significantly associated with absence of MRI: 11/136 (8.1%) versus 2/126 (1.6%) (MRI present) (P = 0.02). No significant factors explained incomplete excision of other tumor types.

CONCLUSION: Preoperative MRI did not significantly affect the overall rate of incomplete tumor excision, but it yielded significantly lower rate of incompletely excised IDC. The reduction of incomplete excisions after MRI was smaller than the rate of a prior treatment change incurred by MRI.}, } @article {pmid18807136, year = {2008}, author = {Tsuchiya, S}, title = {Cytological characteristics of invasive lobular carcinoma of the human breast.}, journal = {Medical molecular morphology}, volume = {41}, number = {3}, pages = {121-125}, pmid = {18807136}, issn = {1860-1480}, mesh = {Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Lobular/diagnosis/*pathology ; Female ; Humans ; Mammary Glands, Human/cytology/pathology ; Neoplasm Invasiveness ; }, abstract = {In contrast to invasive ductal carcinoma, invasive lobular carcinoma (ILC) of the breast is characterized by multiple ipsilateral occurrences and a higher incidence in the contralateral breast. It is therefore necessary to examine thoroughly whether there is any other carcinoma present before any breast-conserving surgery is carried out. We cytologically, histologically, and ultrastructurally investigated ILC and pure scirrhous carcinoma (PSC), a subtype of invasive ductal carcinoma, to establish cytological diagnostic criteria for the differential diagnosis of these two types of carcinoma that have high histological similarity. Cytologically, ILC cells showed linear or isolated cell arrangements and had small nuclei with round homogeneously distributed fine granular chromatin. The cytoplasm was light, and individual cells lacked cohesion. The carcinoma showed a rosary-like configuration. PSC cells, however, showed linear or cordlike arrangements. Individual cells showed a vertical arrangement. PSC cells had a linear cytoplasmic edge and were characterized by nuclear molding with coarse granular chromatin. These cytological findings were supported by histological and ultrastructural findings. These findings may contribute to histological estimation of ILC in preoperative cytological diagnosis.}, } @article {pmid18807122, year = {2009}, author = {Tozaki, M and Yamashiro, N and Suzuki, T and Kawano, N and Ozaki, S and Sakamoto, N and Abe, S and Ogawa, T and Katayama, N and Tsunoda, Y and Fukuma, E}, title = {MR-guided vacuum-assisted breast biopsy: is it an essential technique?.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {121-125}, doi = {10.1007/s12282-008-0074-8}, pmid = {18807122}, issn = {1880-4233}, mesh = {Adult ; Aged ; Biopsy, Needle/instrumentation/methods ; Breast/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography/instrumentation ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: In the United States and Europe, MR-guided vacuum-assisted biopsy (VAB) is required for MR-only visible suspicious lesions that cannot be identified with mammography or ultrasonography. However, it is controversial as to whether MR-guided VAB is essential or not in Japan. The purpose of this study was to clarify the frequency of malignancy among the patients that underwent MR-guided VAB, and to discuss the need for this technique in Japan.

METHODS: This study was approved by the Institutional Review Board of our hospital. A retrospective review was performed of 30 consecutive patients who had undergone MR-guided 11-gauge VAB. The biopsies were performed on a 1.5 T MR scanner using a commercially available biopsy system. All lesions seen with MRI could not be detected by mammography and second-look ultrasonography.

RESULTS: All 30 lesions were assessed as category 4 or 5. The average lesion size of a mass enhancement before biopsy was 0.7 cm, and the average lesion size of a non-mass-like enhancement was 2.3 cm. The average number of cores of VAB was 19. The median time required to perform the VAB procedure was 35 min. The biopsy was successfully performed without important side effects in all patients. Histopathological findings were invasive ductal carcinoma in one (3%); ductal carcinoma in situ (DCIS) in seven (23%); and benign in 22 (73%). In one case, atypical ductal hyperplasia at VAB was upgraded to DCIS at surgical excision.

CONCLUSION: MR-guided VAB can be performed safely and it is needed for MR-only visible suspicious lesions in Japan.}, } @article {pmid18801081, year = {2008}, author = {Kunju, LP and Ding, Y and Kleer, CG}, title = {Tubular carcinoma and grade 1 (well-differentiated) invasive ductal carcinoma: comparison of flat epithelial atypia and other intra-epithelial lesions.}, journal = {Pathology international}, volume = {58}, number = {10}, pages = {620-625}, doi = {10.1111/j.1440-1827.2008.02280.x}, pmid = {18801081}, issn = {1440-1827}, support = {CA090876/CA/NCI NIH HHS/United States ; CA107469/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/metabolism/*pathology ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism ; Cell Nucleus/metabolism/pathology ; Epithelial Cells/pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {The distinction between tubular carcinomas (TC) and invasive well-differentiated (grade 1) ductal carcinoma (IDC) is important given treatment and prognostic differences. Studies have described a strong association between flat epithelial atypia (FEA) and TC. The incidence of FEA associated with grade 1 IDC is not well established. The aim of the present study was to assess morphology and intra-epithelial lesions between 14 TC and 18 grade 1 IDC matched for size. Of 14 TC, eight (57%) had associated FEA, seven (50%) had micropapillary atypical ductal hyperplasia (ADH), three (21%) had low nuclear grade ductal carcinoma in situ (DCIS), and four (29%) had lobular neoplasia. Notably, only two of 18 (11%) grade 1 IDC had associated FEA. Three of 18 (16%) grade 1 IDC had ADH, two (11%) had lobular neoplasia, and seven (39%) had DCIS. All tubular carcinomas were estrogen receptor (ER) positive and negative for Her-2/neu overexpression. All grade 1 IDC were ER positive but 5% also overexpressed Her-2/neu. Axillary lymph node metastasis was present in 11% of grade 1 IDC and absent in TC. A strong association was found between TC, FEA, and micropapillary ADH, which may reflect a biological progression. Despite matching for tumor size, grade 1 IDC have a higher incidence of lymph node metastasis and may have Her-2-neu overexpression compared to TC.}, } @article {pmid18801076, year = {2008}, author = {Lee, SH and Chaung, CR}, title = {Mucinous metaplasia of breast carcinoma with macrocystic transformation resembling ovarian mucinous cystadenocarcinoma in a case of synchronous bilateral infiltrating ductal carcinoma.}, journal = {Pathology international}, volume = {58}, number = {9}, pages = {601-605}, doi = {10.1111/j.1440-1827.2008.02278.x}, pmid = {18801076}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology/surgery ; Cystadenocarcinoma, Mucinous/chemistry/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Mastectomy, Radical ; Metaplasia ; Middle Aged ; Neoplasms, Second Primary/*pathology/surgery ; Ovarian Neoplasms/*pathology/secondary ; }, abstract = {Mammary mucinous cystadenocarcinoma (MCA) is a rare, invasive ductal carcinoma (IDC) of the breast that is virtually identical morphologically to MCA of the ovary, pancreas or appendix. Synchronous bilateral breast tumors, not uncommonly encountered in fibroadenoma and lobular carcinoma, are unusual in IDC. Reported herein is a primary MCA of the right breast coexisting with a bilateral ordinary IDC in a 55-year-old Taiwanese woman who underwent modified radical mastectomy of both breasts with bilateral axillary level I and II lymph node dissection. In the right breast a 2.5 cm unilocular mucus-filled cyst was found. It had complex papillae, some of which were supported by delicate fibrovascular stroma, lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin and an abundance of intracystic extracellular mucin, coexisting with a low-grade ordinary IDC. In the left breast a high-grade ordinary IDC was discovered. The patient had undergone simple abdominal total hysterectomy for myoma uteri along with bilateral salpingo-oophorectomy 10 years previously. Based on pathological studies and a literature review, it is suggested that mammary MCA arises from mucinous metaplasia and macrocystic transformation of ordinary breast carcinoma. A brief discussion of bilateral breast cancers is also given.}, } @article {pmid18798593, year = {2008}, author = {Dragoumis, DM and Tsiftsoglou, AP and Sikou, AD and Assimaki, AS}, title = {Axillary lymph node metastases as the sole clinical site of occult breast carcinoma.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {18}, number = {8}, pages = {517-519}, pmid = {18798593}, issn = {1022-386X}, mesh = {Antineoplastic Agents, Hormonal ; Axilla/pathology ; Breast Neoplasms/drug therapy/*pathology/radiotherapy/surgery ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis/pathology ; Mastectomy, Radical ; Middle Aged ; Tamoxifen/therapeutic use ; }, abstract = {Patients without evidence of breast disease, who present with axillary lymph node metastases, consistent with breast origin, comprise a diagnostic and therapeutic dilemma. We describe such a case of a 47-year-old female, who complained of swelling and pain of the left axilla, but no breast mass was palpable. Although histology identified a metastatic adenocarcinoma in the lymph nodes, numerous tests failed to detect the primary tumor. Immunohistochemistry showed that the resected lymph nodes were positive for both estrogen and progesterone receptors, CEA and Gross Cystic Disease Fluid Protein 15 (GCDFP-15), suggesting the breast as the site of the primary tumor. Left modified radical mastectomy was performed. Pathology revealed an invasive ductal carcinoma, 12 mm in size. The patient received adjuvant chemotherapy and radiation therapy. She is currently being treated with tamoxifen and is well without evidence of disease 2 years after surgery.}, } @article {pmid18795615, year = {2008}, author = {Fu, BM and He, XS and Yu, S and Hu, AB and Ma, Y and Huang, JF}, title = {[Culture and identification of mouse myeloid semimature dendritic cells].}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {30}, number = {4}, pages = {430-435}, pmid = {18795615}, issn = {1000-503X}, mesh = {Animals ; *Cell Culture Techniques ; *Cell Differentiation ; Cells, Cultured ; Cytokines/immunology ; Dendritic Cells/*cytology/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Monocytes/*cytology/immunology ; }, abstract = {OBJECTIVE: To investigate the methods of culturing and identifying mouse myeloid semimature dendritic cell (smDC) in vitro.

METHODS: Myeloid monocytes derived from 6-week-old C57 BL/6 mice were cultured in RPMI-1640 medium containing 10% fetal bovine serum, 2 ng/ml recombinant murine granulocyte macrophage-colony stimulating factor (GM-CSF), and 20 ng/ml recombinant murine interleukin (IL)-4 for 9 days. Then cells were incubated with 40 ng/ml tumor necrosis factor-alpha (TNF-alpha) for 24 hours to obtain smDC. Meanwhile, smDC was differentiated into mature dendritic cell (mDC) or immature dendritic cell (iDC) by treatment with 1 micro/m1 lipopolysaccharide (LPS) or without LPS. The morphological features of smDC were assayed by inverted microscopy and scanning electron microscopy. Surface markers such as CD11c, CD4O, CD8O, CD86, and MHC-II were tested by flow cytometry. IL-1beta, IL-6, IL-12, and IL-10 in the supernatant were tested by ELISA. The activation of allogene lymphocyte (BALB/c mice) stimulated by C57BL/6 myeloid smDC in mixed lymphocyte reaction was examined by Cell Counting Kit-8 in vitro.

RESULTS: The shape of smDC was round or oval-shaped, and the diameter of smDC was about 15 microm. The length of smDC dendrite was between 5 to 10 microm. smDC, iDC, and mDC all expressed high level of CD11 c. The expressions of MHC-II, CD40, CD80, and CD86 on smDC were higher than those of iDC and lower than those of mDC. IL-1beta, IL-6, and IL-12 secretion of smDC was significantly lower than that of mDC (P < 0.01), and IL-12 was significantly lower than that of iDC (P < 0.05), while no significant difference of IL-1beta and IL-6 secretion was found between smDC and iDC (P > 0.05). Furthermore, IL-10 secretion was not significantly different among these three kinds of DCs (P > 0.05). The effect of allogene lymphocytes activation on smDC was significantly lower than that of mDC and positive control (P < 0.01), but had no significant difference when compared with that of iDC and negative control (P > 0.05).

CONCLUSIONS: smDC may be a relatively independent dendritic cell sub-population in terms of function and morphology. It is a feasible way to induce myeloid monocytes to differentiate into smDC using GM-CSF, IL-4, and TNF-alpha in vitro.}, } @article {pmid18790652, year = {2008}, author = {Soria, G and Yaal-Hahoshen, N and Azenshtein, E and Shina, S and Leider-Trejo, L and Ryvo, L and Cohen-Hillel, E and Shtabsky, A and Ehrlich, M and Meshel, T and Keydar, I and Ben-Baruch, A}, title = {Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: a basis for tumor-promoting interactions.}, journal = {Cytokine}, volume = {44}, number = {1}, pages = {191-200}, doi = {10.1016/j.cyto.2008.08.002}, pmid = {18790652}, issn = {1096-0023}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cell Line, Tumor ; Chemokine CCL2/*biosynthesis ; Chemokine CCL5/*biosynthesis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Metastasis/physiopathology ; Pleural Effusion/metabolism ; }, abstract = {The chemokines RANTES (CCL5) and MCP-1 (CCL2) were suggested to contribute, independently, to breast malignancy. In the present study, we asked if the two chemokines are jointly expressed in clinical samples of breast cancer patients, and do they interact in breast tumor cells. We found that RANTES and MCP-1 were expressed by breast tumor cells in primary tumors of Ductal Carcinoma In Situ and of Invasive Ductal Carcinoma, but minimally in normal breast epithelial duct cells. The chemokines were also detected in metastases and pleural effusions. Novel findings showed that co-expression of RANTES and MCP-1 in the same tumor was associated with more advanced stages of disease, suggesting that breast tumors "benefit" from interactions between the two chemokines. Accordingly, MCP-1 significantly promoted the release of RANTES from endogenous pre-made vesicles, in an active process that depended on calcium from intracellular and extracellular sources, and on intracellular transport of RANTES towards exocytosis. Our findings show a chemokine-triggered release of stored pro-malignancy chemokine from breast tumor cells. These observations support a major tumor-promoting role for co-expression of the chemokines in breast malignancy, and agree with the significant association of joint RANTES and MCP-1 expression with advanced stages of breast cancer.}, } @article {pmid18788857, year = {2008}, author = {Chen, YB and Magpayo, J and Rosen, PP}, title = {Sclerosing adenosis in sentinel axillary lymph nodes from a patient with invasive ductal carcinoma: an unusual variant of benign glandular inclusions.}, journal = {Archives of pathology & laboratory medicine}, volume = {132}, number = {9}, pages = {1439-1441}, doi = {10.5858/2008-132-1439-SAISAL}, pmid = {18788857}, issn = {1543-2165}, mesh = {Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/metabolism/*pathology ; Membrane Proteins/biosynthesis ; Neprilysin/biosynthesis ; Sclerosis ; *Sentinel Lymph Node Biopsy ; }, abstract = {Benign glandular inclusions in axillary lymph nodes are very rare events that have to be distinguished from metastatic carcinoma. We report an exceptional instance in which a patient with invasive ductal carcinoma had benign glandular inclusions in the form of sclerosing adenosis in 2 sentinel lymph nodes. The lymph nodes did not contain metastatic carcinoma. Immunohistochemical studies facilitated the correct diagnosis.}, } @article {pmid18786865, year = {2008}, author = {Trombetta, M and Julian, T and Miften, M and McWilliams, W and Kim, Y and Parda, D}, title = {The use of the MammoSite balloon applicator in re-irradiation of the breast.}, journal = {Brachytherapy}, volume = {7}, number = {4}, pages = {316-319}, doi = {10.1016/j.brachy.2008.06.001}, pmid = {18786865}, issn = {1538-4721}, mesh = {Brachytherapy/*instrumentation/methods ; Breast/radiation effects ; Breast Neoplasms/*radiotherapy ; Carcinoma, Intraductal, Noninfiltrating/*radiotherapy ; Female ; Humans ; Neoplasm Recurrence, Local/*radiotherapy ; Radiotherapy/adverse effects ; Radiotherapy, Computer-Assisted ; Treatment Outcome ; }, abstract = {PURPOSE: To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast.

METHODS AND MATERIALS: Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkin's disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkin's disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5-60.3%) of the prescribed dose.

RESULTS: With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard.

CONCLUSIONS: Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients.}, } @article {pmid18779730, year = {2008}, author = {Sepehr, A and Mino-Kenudson, M and Ogawa, F and Brugge, WR and Deshpande, V and Lauwers, GY}, title = {IgG4+ to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other "mass forming" pancreatic lesions.}, journal = {The American journal of surgical pathology}, volume = {32}, number = {12}, pages = {1770-1779}, doi = {10.1097/PAS.0b013e318185490a}, pmid = {18779730}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Ampulla of Vater/*immunology/metabolism/pathology ; Autoimmune Diseases/*immunology/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Diagnosis, Differential ; Female ; Humans ; *Immunoglobulin G ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/pathology ; Pancreatitis/*immunology/metabolism/pathology ; Plasma Cells/*immunology/metabolism ; ROC Curve ; Sensitivity and Specificity ; }, abstract = {Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.}, } @article {pmid18776959, year = {2008}, author = {Woodiwiss, AJ and Badenhorst, D and Sliwa, K and Brooksbank, R and Essop, R and Sareli, P and Norton, GR}, title = {Beta1- and alpha2c-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry.}, journal = {Cardiovascular journal of Africa}, volume = {19}, number = {4}, pages = {188-193}, pmid = {18776959}, issn = {1995-1892}, mesh = {Black People/*genetics ; Cardiomyopathy, Dilated/drug therapy/ethnology/*genetics/pathology/physiopathology ; Cardiovascular Agents/therapeutic use ; Case-Control Studies ; Disease Progression ; Drug Therapy, Combination ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; Prospective Studies ; Receptors, Adrenergic, alpha-2/*genetics ; Receptors, Adrenergic, beta-1/*genetics ; Risk Factors ; Severity of Illness Index ; South Africa ; Stroke Volume/drug effects/genetics ; Treatment Outcome ; Ventricular Function, Left/drug effects/genetics ; }, abstract = {BACKGROUND: Although the beta1-adrenoreceptor (AR) Gly389Arg and alpha2c-AR Del322-325 gene variants are associated with the response to beta-AR-blocker therapy, whether this effect is associated with the risk for heart failure, or the severity or progression of heart failure is uncertain.

AIMS: To assess the relationship between Gly389Arg and Del322-325 variants and the presence, severity and progression of idiopathic dilated cardiomyopathy (IDC) in 403 black South African patients.

METHODS: Genotypes were identified using a restriction fragment length polymorphism-based technique and automated sequencing. Left ventricular ejection fraction (LVEF) and dimensions were determined at baseline and in 132 patients after six months of standard medical therapy excluding beta-AR-blockers (not indicated as standard care at the time of completing this study).

RESULTS: All patients and controls genotyped for the alpha2c-AR variant were homozygous for the Del322-325 (risk) allele. The Gly389Arg polymorphism was not associated with IDC (control n = 429) (Arg389 allele homozygosity: odds ratio = 1.03, confidence limits = 0.78-1.35), nor did it predict LVEF and cavity dimensions either before or after therapy.

CONCLUSION: In patients homozygous for the risk allele of the alpha2c-AR variant, the beta1-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving beta-AR-blockers.}, } @article {pmid18774496, year = {2008}, author = {Reena, RM and Mastura, M and Siti-Aishah, MA and Munirah, MA and Norlia, A and Naqiyah, I and Rohaizak, M and Sharifah, NA}, title = {Minichromosome maintenance protein 2 is a reliable proliferative marker in breast carcinoma.}, journal = {Annals of diagnostic pathology}, volume = {12}, number = {5}, pages = {340-343}, doi = {10.1016/j.anndiagpath.2008.04.001}, pmid = {18774496}, issn = {1532-8198}, mesh = {Adenocarcinoma/*metabolism/secondary ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism/secondary ; Carcinoma, Lobular/metabolism/secondary ; Cell Cycle Proteins/*metabolism ; Cell Nucleus/metabolism/pathology ; Cell Proliferation ; Female ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins/*metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.}, } @article {pmid18771601, year = {2008}, author = {Ismail, NI and Kaur, G and Hashim, H and Hassan, MS}, title = {S100A4 overexpression proves to be independent marker for breast cancer progression.}, journal = {Cancer cell international}, volume = {8}, number = {}, pages = {12}, pmid = {18771601}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.

METHODS: S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.

RESULTS: S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.

CONCLUSION: S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.}, } @article {pmid18765968, year = {2008}, author = {Calişkan, M and Ciftçi, O and Güllü, H and Müderrisoğlu, H}, title = {The effect of carvedilol therapy on coronary flow reserve in patients with idiopathic dilated cardiomyopathy.}, journal = {Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir}, volume = {36}, number = {4}, pages = {247-252}, pmid = {18765968}, issn = {1016-5169}, mesh = {Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Blood Flow Velocity ; Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/*diagnostic imaging/*drug therapy ; Carvedilol ; Coronary Vessels/*diagnostic imaging ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Propanolamines/*therapeutic use ; Treatment Failure ; Vasodilator Agents/*therapeutic use ; }, abstract = {OBJECTIVES: We evaluated the effect of carvedilol, a nonselective beta-blocker with vasodilating action, on coronary flow reserve (CFR) in patients with idiopathic dilated cardiomyopathy (IDC).

STUDY DESIGN: Twenty-four patients (17 males, 7 females; mean age 57+/-11 years) with IDC were consecutively enrolled. After obtaining clinical and hemodynamic stabilization, transthoracic echocardiography was performed including CFR measurement and carvedilol therapy was initiated with 3.125 mg twice daily and titrated to a target dose of 25 mg twice daily. Twenty-three patients reached the target dose in a mean of 11+/-3 weeks. The mean duration of carvedilol therapy was 19+/-3 weeks, after which echocardiography was repeated and findings were recorded at baseline and after dipyridamole infusion. Clinical and echocardiographic findings were compared with those of 23 age- and sex-matched patients (13 males, 10 females; mean age 55+/-4 years) with atypical chest pain.

RESULTS: Compared to the control group, left ventricular end-diastolic and end-systolic volumes, left ventricular mass index, and isovolumic relaxation time were significantly higher and ejection fraction was significantly lower in the IDC group. Before carvedilol therapy, patients with IDC had a significantly higher baseline diastolic peak flow velocity (DPFV) and a significantly lower CFR; however, hyperemic DPFV was similar in the two groups. After carvedilol therapy, left ventricular end-systolic volume decreased significantly and ejection fraction increased significantly. Decreases in baseline DPFV and hyperemic DPFV were slight and there was no improvement in CFR. Even after elimination of the confounding effect of rate-pressure product using analysis of covariance, pre- and post-treatment CFR remained similar.

CONCLUSION: Carvedilol therapy does not improve coronary microvascular functions in patients with IDC.}, } @article {pmid18765526, year = {2008}, author = {Kikuchi, S and Honda, K and Tsuda, H and Hiraoka, N and Imoto, I and Kosuge, T and Umaki, T and Onozato, K and Shitashige, M and Yamaguchi, U and Ono, M and Tsuchida, A and Aoki, T and Inazawa, J and Hirohashi, S and Yamada, T}, title = {Expression and gene amplification of actinin-4 in invasive ductal carcinoma of the pancreas.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {17}, pages = {5348-5356}, doi = {10.1158/1078-0432.CCR-08-0075}, pmid = {18765526}, issn = {1078-0432}, mesh = {Actinin/antagonists & inhibitors/*genetics ; Aged ; Animals ; Carcinoma, Pancreatic Ductal/*genetics ; Cell Line, Tumor ; Female ; *Gene Amplification ; Gene Expression ; Humans ; Male ; Mice ; Mice, SCID ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Pancreatic Neoplasms/*genetics ; Transfection ; }, abstract = {PURPOSE: An invasive growth pattern is one of the hallmarks of pancreatic ductal carcinoma. Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer.

EXPERIMENTAL DESIGN: The expression of actinin-4 was examined immunohistochemically in 173 cases of invasive pancreatic ductal carcinoma. The copy number of the actinin-4 (ACTN4) gene was calculated by fluorescence in situ hybridization. The expression of actinin-4 was stably knocked down by short hairpin RNA, and tumorigenicity was evaluated by orthotopic implantation into mice with severe combined immunodeficiency.

RESULTS: The expression level of actinin-4 was increased in 109 (63.0%) of 173 cases of pancreatic cancer. Kaplan-Meier survival curves revealed that patients with increased expression of actinin-4 had a significantly poorer outcome (P=0.00001, log-rank test). Multivariate analysis by the Cox proportional hazard model showed that high expression of actinin-4 was the most significant independent negative predictor of survival (hazard ratio, 2.33; P=0.000009). Amplification (defined as more than four copies per interphase nucleus) of the ACTN4 gene was detected in 11 (37.9%) of 29 cases showing increased expression of actinin-4. Knockdown of actinin-4 expression inhibited the destructive growth of cancer cells in the pancreatic parenchyma.

CONCLUSION: Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified. Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.}, } @article {pmid18764880, year = {2008}, author = {Cui, LF and Guo, XJ and Wei, J and Liu, FF and Fan, Y and Lang, RG and Gu, F and Zhang, XM and Fu, L}, title = {Overexpression of TNF-alpha and TNFRII in invasive micropapillary carcinoma of the breast: clinicopathological correlations.}, journal = {Histopathology}, volume = {53}, number = {4}, pages = {381-388}, doi = {10.1111/j.1365-2559.2008.03128.x}, pmid = {18764880}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/pathology ; Carcinoma, Papillary/blood supply/metabolism/*pathology ; Cell Proliferation ; Female ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neovascularization, Pathologic/pathology ; Receptors, Tumor Necrosis Factor, Type II/*metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {AIMS: Angiogenesis is essential for tumour growth and metastasis and tumour necrosis factor (TNF)-alpha is a potent angiogenic factor. Invasive micropapillary carcinoma of the breast (IMPC), a rare subtype of breast cancer, possesses a lymphotropic nature with a high incidence of lymph node metastasis and poor prognosis. The aim was to evaluate the role of TNF-alpha and its receptor TNFRII in the vascular development and metastasis of IMPC.

METHODS AND RESULTS: One hundred cases of IMPC and 97 cases of invasive ductal carcinoma, not otherwise specified (IDC) were studied in parallel by immunohistochemistry for TNF-alpha and TNFRII, and microvessel density (MVD) of the tumours was measured. The results showed that the expression of TNF-alpha and TNFRII and the MVD were higher in IMPC than in IDC (P < 0.05). In IMPC, MVD was significantly increased in those with lymph node metastasis compared with those without nodal metastasis (P = 0.001). TNF-alpha expression showed a significant positive correlation with the rate of proliferation, histological grade, lymph node metastasis and MVD (P < 0.05), whereas expression of TNFRII was correlated with TNF-alpha expression and the proliferation of tumour cells in IMPC (P < 0.05).

CONCLUSIONS: Expression of TNF-alpha and TNFRII might play an important role in the angiogenesis, tumour cell proliferation and metastasis of IMPC. These markers could represent new targets for therapeutic intervention, i.e. blocking of TNF-alpha and its signal transduction could be a promising tool for treatment.}, } @article {pmid18763593, year = {2008}, author = {Vybornykh, DE and Ivanov, SV and Savchenko, VG and Gemdzhian, EG}, title = {[Somatogenic and somatogenically provoked psychoses in blood diseases].}, journal = {Terapevticheskii arkhiv}, volume = {80}, number = {7}, pages = {38-43}, pmid = {18763593}, issn = {0040-3660}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Hematologic Diseases/*complications ; Humans ; Incidence ; Male ; Middle Aged ; Psychotic Disorders/epidemiology/*etiology ; Retrospective Studies ; Risk Factors ; Russia/epidemiology ; Surveys and Questionnaires ; }, abstract = {AIM: To detect risk factors (RF) to develop somatogenic psychoses (SP) in blood diseases.

MATERIAL AND METHODS: A total of 107 SP patients were examined with the disease corresponding to diagnostic points F05 or F06 (IDC-10).

RESULTS: The following RF were identified: cytostatic drugs with or without glucocorticosteroids, glucocorticosteroids alone, interferon-alpha, viral encephalitis, neuroleukemia. Single obligatory specific factors which bring manifestation of certain psychoses were not identified. SP in each of the considered hematological malignancies are related with various factors.

CONCLUSION: The findings suggest polyfactor etiology of SP including some schemes of chemotherapy, some type of blood disease, specific premorbid features and mental disease burden. We suggest that the clinical picture, dynamics and prognosis of SP in blood diseases may be caused by a profile of factors typical for each disease.}, } @article {pmid18757140, year = {2008}, author = {Kefeli, M and Yildiz, L and Akpolat, I and Balci, P and Ozen, N}, title = {The coexistence of invasive ductal carcinoma and malignant phyllodes tumor with liposarcomatous and chondrosarcomatous differentiation in the same breast in a post-osteosarcoma case.}, journal = {Pathology, research and practice}, volume = {204}, number = {12}, pages = {919-923}, doi = {10.1016/j.prp.2008.07.004}, pmid = {18757140}, issn = {0344-0338}, mesh = {Adult ; Amputation, Surgical ; Antineoplastic Combined Chemotherapy Protocols ; Bone Neoplasms/pathology/therapy ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Differentiation ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Second Primary/metabolism/*pathology ; Osteosarcoma/pathology/therapy ; Phyllodes Tumor/metabolism/*pathology ; Radiotherapy ; Tibia/pathology ; }, abstract = {Malignant phyllodes tumors of the breast are rare biphasic neoplasms, the stromal component of which may show homologous and heterologous sarcomatous elements. Malignant epithelial transformation is rare. It has been reported in a few cases of in situ and infiltrating ductal or lobular carcinoma. Rarely, breast carcinomas and phyllodes tumors may also develop in the same breast independent of each other. To our knowledge, this is the first case of two different types of tumor occurring in the same breast at the same time in a post-osteosarcoma case.}, } @article {pmid20424657, year = {2008}, author = {Hamed, ST and Abdo, MH and Ahmed, HH}, title = {Breast discharge: ultrasound and Doppler evaluation.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {20}, number = {3}, pages = {262-270}, pmid = {20424657}, issn = {1110-0362}, abstract = {BACKGROUND: Nipple discharge causes discomfort and anxiety to many women. Nipple discharge is most commonly associated with endocrine alterations and/or medications. These often result in duct ectasia and/or fibrocystic changes that may lead to discharge from one or several ducts. The most common cause of clinically significant discharge is intraductal growth of the ductal epithelium, due to hyperplasia, micropapillary proliferation, solitary papillomas and/or ductal carcinoma (both in situ and invasive). The aim of the study was to evaluate the role of the gray-scale ultrasound and colour Doppler in the diagnosis of intraductal pathology in patients with nipple discharge.

PATIENTS AND METHODS: One hundred & seven patients were included in the study, (age range 23-65years). Standard mammographic views were taken. Ultrasound evaluation was performed for all cases; ductography for 20 cases and ductoscopy for 3 cases. US guided fine needle biopsy was done in 7 cases; microducectomy of affected duct was done in 20 cases and major duct excision in 5cases. Fibro-optic Ductoscopy is performed for 3 cases.

RESULTS: Revision of biopsy specimens of 17 cases with intraluminal masses detected by US revealed: Six cases with intraductal carcinoma, intraductal papilloma in 7 cases, 1 case of ductal papillomatosis. Three cases showed atypical cells: Intraductal papilloma with atypia in 2 cases, proliferative hyperplasia with atypia in one case. Eighty eight cases had simple duct ectasia (51 bilateral multiple and 37 focal duct ectasia). No dilated ducts were detected in 2 cases. Fibro-optic Ductoscopy confirmed the presence of intraductal papilloma in one case, carcinoma in one case, no intraductal masses in the third case. A 6 months follow-up was requested for all cases with no detected intra luminal pathology. Ultrasound examination is highly sensitive (100%) but less specific (82.4%) in diagnosis of intraductal pathology. Colour & power Doppler are sensitive (94%) in detecting flow in intraductal echogenic masses to differentiate them from insipissated secretions. Colour and power Doppler raises specificity and diagnostic accuracy to 100%. Ductography is an underused procedure that is sensitive (100%) but less specific (60%) in characterization of intraductal filling defects.

CONCLUSION: Ultrasonography is a mandatory complement to mammography in these cases, US guided fine needle biopsy is minimally invasive technique in confirming the diagnosis of suspicious mass. Ultrasound may also be a guide to fibro-optic ductoscope.

KEY WORDS: Ductography - Nipple discharge - Intraductal carcinoma - Intraductal papilloma - In situ ductal carcinoma - Invasive ductal carcinoma - Duct ectasia - Breast ductoscopy.}, } @article {pmid18752050, year = {2008}, author = {Murillo-Ortiz, B and Pérez-Luque, E and Malacara, JM and Daza-Benítez, L and Hernández-González, M and Benítez-Bribiesca, L}, title = {Expression of estrogen receptor alpha and beta in breast cancers of pre- and post-menopausal women.}, journal = {Pathology oncology research : POR}, volume = {14}, number = {4}, pages = {435-442}, pmid = {18752050}, issn = {1219-4956}, mesh = {Adult ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Estradiol/blood ; Estrogen Receptor alpha/*biosynthesis ; Estrogen Receptor beta/*biosynthesis ; Female ; Follicle Stimulating Hormone/blood ; Humans ; Immunohistochemistry ; Middle Aged ; Postmenopause/*metabolism ; Premenopause/*metabolism ; Radioimmunoassay ; }, abstract = {Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in pre- and post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p < 0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar post-menopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p < 0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.}, } @article {pmid18751874, year = {2009}, author = {Kondo, NI and Yoshida, S and Kajiyama, H and Nagasaka, T and Uematsu, T}, title = {Metastasis of breast cancer to a uterine leiomyoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {157-161}, doi = {10.1007/s12282-008-0069-5}, pmid = {18751874}, issn = {1880-4233}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Hysterectomy ; Leiomyoma/*pathology/surgery ; Middle Aged ; Tomography, X-Ray Computed ; Treatment Outcome ; Uterine Neoplasms/pathology/*secondary/surgery ; }, abstract = {Metastasis of breast cancer to a uterine leiomyoma is rare. We review the clinicopathological features of breast cancer metastasis to a uterine leiomyoma and discuss possible effective treatment. We describe a case of a woman who presented with abdominal discomfort after undergoing mastectomy for breast cancer. At the time of mastectomy, imaging showed osseous metastases involvement to the right kidney. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Microscopic examination disclosed carcinoma of breast origin localized within the leiomyoma. To date, the patient is alive and asymptomatic after treatment with anastozole and capecitabine for 11 months. Per reports in the literature, abnormal uterine bleeding or a rapidly growing leiomyoma may be symptomatic of breast cancer metastasis to a uterine leiomyoma, especially if a patient has a previous diagnosis of invasive ductal carcinoma of the breast. Palliative hysterectomy can potentially improve prognosis in patients whose cancer is restricted to a uterine leiomyoma with or without involvement of lymph nodes, and may offer relief of genital tract symptoms in patients who have widespread involvement of non-life-threatening metastases.}, } @article {pmid18723312, year = {2009}, author = {Polom, K and Murawa, D and Wasiewicz, J and Nowakowski, W and Murawa, P}, title = {The role of sentinel node biopsy in ductal carcinoma in situ of the breast.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {35}, number = {1}, pages = {43-47}, doi = {10.1016/j.ejso.2008.07.007}, pmid = {18723312}, issn = {1532-2157}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/*pathology/surgery ; Carcinoma, Ductal/*pathology/surgery ; Chi-Square Distribution ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis ; Middle Aged ; *Sentinel Lymph Node Biopsy ; Stereotaxic Techniques ; Survival Analysis ; }, abstract = {AIM: Sentinel node biopsy (SNB) is an accepted alternative to lymphadenectomy in the case of invasive breast carcinoma, although the sentinel node's role in ductal carcinoma in situ (DCIS) diagnosed on core needle biopsy has not been well defined nevertheless guidelines recommend this procedure. The purpose of this study was to determine the diagnostic value of sentinel nodes in female patients with primary DCIS using core needle stereotactic biopsy.

MATERIAL AND METHODS: Between the years 2000 and 2005, 261 patients were diagnosed with DCIS by core needle biopsy. In this group, 183 patients underwent SNB to determine lymph node involvement. Those patients with metastases to the sentinel node underwent axillary lymphadenectomy.

RESULTS: In the group of 183 patients that underwent SNB, 10 patients (5.5%) showed metastases to the sentinel lymph node. Histopathological studies of the primary lesions of these 10 patients revealed invasive ductal carcinoma in 6 cases (3.5%) and 1 case (0.5%) of invasive lobular carcinoma. Only 3 of the patients (1.5%) were given a final diagnosis of DCIS with metastases to sentinel lymph nodes, of which 2 cases were DCIS and 1 case was DCIS with microinvasion. Axillary lymphadenectomy performed on patients with abnormal SNB showed involvement of other axillary lymph nodes in 4 patients.

CONCLUSIONS: SNB as a diagnostic tool in DCIS remains controversial as the number of cases of axillary lymph node metastases is minuscule. The biggest clinical challenge in this situation is a group of patients with primary diagnosis of DCIS in which invasive components are seen by mammotomic biopsy.}, } @article {pmid18723155, year = {2008}, author = {Hruska, CB and Boughey, JC and Phillips, SW and Rhodes, DJ and Wahner-Roedler, DL and Whaley, DH and Degnim, AC and O'Connor, MK}, title = {Scientific Impact Recognition Award: Molecular breast imaging: a review of the Mayo Clinic experience.}, journal = {American journal of surgery}, volume = {196}, number = {4}, pages = {470-476}, pmid = {18723155}, issn = {1879-1883}, support = {R21 CA110162-01/CA/NCI NIH HHS/United States ; R21 CA110162-02/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging ; Equipment Design ; False Negative Reactions ; False Positive Reactions ; Female ; *Gamma Cameras ; Humans ; Radiation Dosage ; Radionuclide Imaging ; Radiopharmaceuticals ; Sensitivity and Specificity ; Technetium Tc 99m Sestamibi ; }, abstract = {BACKGROUND: Molecular breast imaging (MBI) depicts functional uptake of targeted radiotracers in the breast using dedicated gamma cameras.

METHODS: MBI studies were performed under several institutional protocols evaluating the use of MBI in screening and diagnosis.

RESULTS: By using a single-head system, sensitivity for breast cancer detection was 85% (57 of 67) overall and 29% for tumors 5 mm or less in diameter. Sensitivity improved to 91% (117 of 128) overall and 69% for tumors 5 mm or less using a dual-head system. In 650 high-risk patients undergoing breast cancer screening, MBI detected 7 cancers, 5 of which were missed on mammography. In 24 of 149 (16%) breast cancer patients MBI detected additional disease not seen on mammography. The sensitivity of MBI was 88% (83 of 94) for invasive ductal carcinoma, 79% (23 of 29) for invasive lobular carcinoma, and 89% (25 of 28) for ductal carcinoma in situ.

CONCLUSIONS: MBI can detect invasive ductal carcinoma, ductal carcinoma in situ, and invasive lobular carcinoma. It has a promising role in evaluating the extent of disease and multifocal disease in the breast for surgical treatment planning.}, } @article {pmid18720524, year = {2008}, author = {Loo, LW and Ton, C and Wang, YW and Grove, DI and Bouzek, H and Vartanian, N and Lin, MG and Yuan, X and Lawton, TL and Daling, JR and Malone, KE and Li, CI and Hsu, L and Porter, PL}, title = {Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer.}, journal = {Genes, chromosomes & cancer}, volume = {47}, number = {12}, pages = {1049-1066}, pmid = {18720524}, issn = {1098-2264}, support = {R01 CA095717-01/CA/NCI NIH HHS/United States ; R01 CA095717/CA/NCI NIH HHS/United States ; R01 CA085913/CA/NCI NIH HHS/United States ; R01 CA085913-05/CA/NCI NIH HHS/United States ; R01 CA085913-01/CA/NCI NIH HHS/United States ; R01 CA095717-04/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics/pathology ; Case-Control Studies ; DNA, Neoplasm/metabolism ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; *Loss of Heterozygosity ; Polymorphism, Single Nucleotide ; Receptors, Estrogen/*analysis/genetics ; Tissue Array Analysis ; }, abstract = {The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole-genome study of 166 archival estrogen receptor (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue of LOH in 16q.}, } @article {pmid18720457, year = {2008}, author = {Weigelt, B and Horlings, HM and Kreike, B and Hayes, MM and Hauptmann, M and Wessels, LF and de Jong, D and Van de Vijver, MJ and Van't Veer, LJ and Peterse, JL}, title = {Refinement of breast cancer classification by molecular characterization of histological special types.}, journal = {The Journal of pathology}, volume = {216}, number = {2}, pages = {141-150}, doi = {10.1002/path.2407}, pmid = {18720457}, issn = {1096-9896}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*classification/genetics/pathology ; Carcinoma, Ductal, Breast/*classification/genetics/pathology ; Cluster Analysis ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Signal Transduction/genetics ; Statistics, Nonparametric ; }, abstract = {Most invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological 'special types'. These special-type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision-making is increasingly governed by the molecular classification of breast cancer (luminal, basal-like, HER2+). The molecular classification is derived from mainly IDC NOS and it is unknown whether this classification applies to all histological subtypes. We aimed to refine the breast cancer classification systems by analysing a series of 11 histological special types [invasive lobular carcinoma (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and medullary carcinoma] using immunohistochemistry and genome-wide gene expression profiling. Hierarchical clustering analysis confirmed that some histological special types constitute discrete entities, such as micropapillary carcinoma, but also revealed that others, including tubular and lobular carcinoma, are very similar at the transcriptome level. When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like, HER2+), whereas histological special-type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal-like transcriptome, providing strong circumstantial evidence that basal-like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies.}, } @article {pmid18714568, year = {2008}, author = {Kaya, H and Erbarut, I and Ozkan, N and Bekiroğlu, N and Sen, S and Abaciğlu, U}, title = {Immunoexpression of HER family, neuregulin, MAPK and AKT in invasive ductal carcinomas of the breast.}, journal = {European journal of gynaecological oncology}, volume = {29}, number = {4}, pages = {350-356}, pmid = {18714568}, issn = {0392-2936}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; ErbB Receptors/metabolism ; Female ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases/*metabolism ; Neuregulins/*metabolism ; Protein-Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {BACKGROUND: The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand neuregulinalpha (NRGalpha) and the most important pathways activated by HER receptors that are mitogen-activated protein kinase (MAPK) and serine/threonine kinase (AKT) in invasive ductal carcinomas of the breast, not otherwise specified (IDC-NOS).

METHODS: 59 of the IDC-NOS of the breast were studied for ER, PR, EGFR, c-erbB-2, c-erbB-3, c-erbB-4, neuregulin Ab-3, phospho-AKT, and phospho-p44/42 map kinase using the streptavidin-biotin horseradish method.

RESULTS: Of the 59 tumours, 44 (75%) were ER+, 37 (63%) PR+, four (7%) EGFR+, seven (12%) c-erbB-2+, seven (12%) c-erbB-3+ and 14 (24%) c-erbB-4+alpha. Strong cytoplasmic and/or nuclear immunoexpression was revealed in 17 (29%) cases for NRGalpha, 13 (22%) cases for p-AKT, and nuclear immunoexpression with p-MAPK was found in 17 (29%) cases.

CONCLUSION: The results suggest that high-grade breast carcinomas are not only associated with ER/PR- negativity, but seem to be activated by receptor tyrosine kinase growth factors.}, } @article {pmid18701411, year = {2008}, author = {Yamaguchi, J and Ohtani, H and Nakamura, K and Shimokawa, I and Kanematsu, T}, title = {Prognostic impact of marginal adipose tissue invasion in ductal carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {130}, number = {3}, pages = {382-388}, doi = {10.1309/MX6KKA1UNJ1YG8VN}, pmid = {18701411}, issn = {0002-9173}, mesh = {Adipose Tissue/*pathology ; Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; }, abstract = {This study aimed to investigate whether adipose tissue invasion (ATI) of cancer cells at the tumor margin influenced lymph node status and prognosis in patients with invasive ductal carcinoma of the breast. Data for 245 patients with breast cancer with marginal ATI were clinicopathologically compared with data for 65 patients without ATI. We also examined the value of the combination of ATI and peritumoral lymphatic vessel invasion (LVI). The frequency of axillary lymph node metastases was 40.7% in patients with ATI (99/243) and 11.3% in patients without ATI (7/62; P<.0001), and ATI was an independent factor influencing nodal metastasis. Patients with ATI had a poorer prognosis than patients without ATI (10-year disease-free survival, 76% and 94%, respectively; P=.0323). In addition, patients without ATI or LVI had neither lymph node metastasis (n=52) nor recurrent disease (n=53). ATI is one of the biologic indicators of tumor aggressiveness.}, } @article {pmid18686831, year = {2008}, author = {Mayun, AA and Pindiga, UH and Babayo, UD}, title = {Pattern of histopathological diagnosis of breast lesions in Gombe, Nigeria.}, journal = {Nigerian journal of medicine : journal of the National Association of Resident Doctors of Nigeria}, volume = {17}, number = {2}, pages = {159-162}, doi = {10.4314/njm.v17i2.37375}, pmid = {18686831}, issn = {1115-2613}, mesh = {Adult ; Breast Diseases/epidemiology/*pathology ; Breast Neoplasms/epidemiology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Female ; Humans ; Middle Aged ; Nigeria/epidemiology ; Retrospective Studies ; }, abstract = {BACKGROUND: Diseases of the breast are common and include problems, related to pregnancy and lactation, abscesses and other inflammatory conditions, nonneoplastic proliferative disorders and neoplasms. No known previous histopathological analysis has been done in our setting to classify breast lesions. The purpose of this study is to review all cases of breast diseases seen in the department over a six-year period and to determine the pattern of histological diagnosis of breast diseases in our setting.

METHODS: This was a hospital based retrospective study where our bench record books were used to identify all the breast lesions after which the Haematoxylin and Eosin stained slides and the request cards were retrieved. The slides were reviewed based on the diagnostic criteria by Juan Rosai.

RESULTS: A total of 291 breast lesions were seen in the department. One hundred and seventy three (59.5%) of these were inflammatory non-neoplastic proliferative and benign neoplastic disorders, while 118 (40.5%) were malignant neoplasms. Fibroadenoma was the commonest benign breast lesion with 69 (23.7%) cases. Of all the malignancies, invasive ductal carcinoma was the most frequent (68.6%). Breast cancer was found most frequently in the 4th decade (32.2%), followed by the 5th decade (24.6%) of life.

CONCLUSION: Female breast cancer was quite common in this study and most of our patients presented with advanced disease.}, } @article {pmid18681321, year = {2008}, author = {Li, J and Yang, SJ and Zhao, XL and Zhang, YQ and Li, KN and Cui, JH and Li, J}, title = {[Significant increase of glucose transport activity in breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {103-108}, pmid = {18681321}, issn = {0529-5807}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Glucose/*physiology ; Glucose Transport Proteins, Facilitative/genetics/metabolism ; Glucose Transporter Type 1/genetics/*metabolism ; Humans ; Prognosis ; }, abstract = {OBJECTIVE: To study the expression level and significance of glucose transporter 1 (Glut-1) in normal breast tissue, adenosis, adenoma and breast carcinoma.

METHODS: A total of 147 cases of female breast tissue samples, including 92 cases of invasive ductal carcinoma, 26 cases of breast fibroadenoma, 24 cases of breast adenosis and 5 cases of normal breast tissues, were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry (EnVision method) and Western blot, and its mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTS: In normal breast tissue and benign lesions of the breast, Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia. In contrast, the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P = 0.0002) with protein expression predominantly in cellular membrane and lesser in cytoplasm. Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma (P =0.001 for protein; P <0.05 for mRNA) and adenosis (P =0.001 for protein; P < 0.05 for mRNA). There was a significant difference among groups (P = 0.0002 for protein; P = 0.0001 for mRNA).

CONCLUSIONS: Glucose transport activity, as indicated by Glut-1 protein and its mRNA expression, significantly increases in breast carcinoma than non-cancerous lesions. The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation, invasion and metastasis, implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.}, } @article {pmid18681318, year = {2008}, author = {Lü, YL and Zhong, M and Liu, L and Wei, LX and Zhao, P}, title = {[Clinicopathologic significance of chromosome 17 polysomy in breast cancer].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {88-91}, pmid = {18681318}, issn = {0529-5807}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics ; *Chromosome Aberrations ; Chromosomes, Human, Pair 17/*genetics ; *Gene Amplification ; Gene Dosage ; Gene Expression Regulation, Neoplastic/genetics ; Genes, erbB-2/*genetics ; Humans ; }, abstract = {OBJECTIVE: To investigate the clinicopathological significance of chromosome 17 polysomy in breast cancer.

METHODS: Retrospective study of 200 cases of breast cancer including 106 cases of invasive ductal carcinoma and 94 cases of in-situ carcinoma was performed by fluorescence in-situ hybridization (FISH) to explore the relationship between chromosome 17 polysomy and age, nuclear atypia, lymphatic metastasis, HER2 gene amplification and HER2 protein expression.

RESULTS: Twenty-six percent (52/200) of chromosome 17 polysomy was detected in 200 cases of breast ductal carcinoma, all of which were invasive ductal carcinoma. Overall 52. 8% (52/180) of invasive ductal carcinoma cases showed chromosome 17 polysomy, which was correlated to HER2 gene amplification (P = 0.000) and HER-2 protein expression (P=0.000), and to HER2 expression combined with HER2 gene amplification (P=0.001). Chromosome 17 polysomy with or without HER2 gene amplification was also associated with high-grade nuclear atypia (P = 0.012 or P = 0.010) and lymphatic metastasis (P = 0.002 or P = 0.009). However, chromosome 17 polysomy with or without HER2 gene amplification was not correlative with the age of patients (P = 1. 000 or P = 0. 415).

CONCLUSION: Chromosome 17 polysomy may be related to the nuclear atypia, metastasis, HER2 gene amplification of invasive ductal carcinoma and thus a worse prognosis of the patients.}, } @article {pmid18681317, year = {2008}, author = {Gao, LX and Yang, GZ and Ding, HY and Li, L}, title = {[Morphological features of basal-like subtype invasive carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {37}, number = {2}, pages = {83-87}, pmid = {18681317}, issn = {0529-5807}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Basal Cell/*pathology ; ErbB Receptors/genetics ; Female ; Genes, erbB-2/physiology ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Magnetic Resonance Imaging ; Male ; Mammography/instrumentation/methods ; Neoplasm Invasiveness/physiopathology ; Prognosis ; Receptor, ErbB-2/*analysis/genetics ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; Ultrasonography/methods ; }, abstract = {OBJECTIVE: To summarize the morphological features of basal-like subtype of invasive breast carcinoma (BLSIBC), and to look for diagnostic clues for its recognition.

METHODS: Immunohistochemistry was performed in 109 cases of invasive ductal carcinoma, with CK5/6, CK14, CK8/ 18, 34betaE12, calponin, p63, CD10, ER, PR and c-erbB-2 monoclonal antibodies. Five subtypes were classified according to immunophenotypes: luminal A subtype (ER+/HER2-), luminal B subtype (ER+/ HER2+), normal breast-like subtype (ER/HER2-), HER2-overexpressing subtype and BLSIBC which was identified with at least one kind of basal-like cytokeratins or markers of myoepithelium and ER/HER2. The microscopic features of basal-like subtype were also analyzed.

RESULTS: The number of luminal A case was 48 (44.0%), luminal B 15 (13.8%), HER2 over-expressing 15 (13.6%), normal breast-like 10 (9.1%), basal-like subtype 19 (17.4%). Besides, the other two cases expressed c-erbB-2 or/and ER plus markers for myoepithelium, thus were excluded from all the five mentioned subtypes. Of the 19 basal-like subtype, CK5/6 was expressed in 16 cases, CK8/18 in 17 cases, CK14 in 11 cases, 34betaE12 in 18 cases, p63 in 5 cases, CD10 in 6 cases, and calponin in 1 case. The diameter of the BLSIBC cases was 1.2-7 cm (averagely 3.9 cm) , and in 6 cases, the tumor diameter was >5 cm. Only one case displayed extensive in situ component, 9 cases were grade 2, and 9 cases were grade 3. Compared to non basal subtype, there were significantly more high grade cases (P <0.01). The morphological features of basal-like subtype were summarized as the followings: pushing margin (13 cases), lymphocytic tissue hyperplasia (18 cases), nest or sheet arrangement (18 cases), nucleus grade 3 and scattered giant or bizarre nuclei (17 cases), syncytial growth (7 cases), and comedo-like necrosis (17 cases). The frequency of these features were significantly more common than non basal subtype (P <0.01).

CONCLUSION: The morphologic diagnostic features of BLSIBC are pushing margins, lymphocyte infiltration, comedo-like necrosis, gigantic cell and syncytial growth.}, } @article {pmid18680763, year = {2008}, author = {Cirone, M and Lucania, G and Aleandri, S and Borgia, G and Trivedi, P and Cuomo, L and Frati, L and Faggioni, A}, title = {Suppression of dendritic cell differentiation through cytokines released by Primary Effusion Lymphoma cells.}, journal = {Immunology letters}, volume = {120}, number = {1-2}, pages = {37-41}, doi = {10.1016/j.imlet.2008.06.011}, pmid = {18680763}, issn = {0165-2478}, mesh = {*Cell Differentiation/drug effects ; Cell Line, Tumor ; Culture Media, Conditioned/pharmacology ; Cytokines/*metabolism ; Dendritic Cells/*cytology/drug effects ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lymphoma, Primary Effusion/*metabolism ; Phenotype ; }, abstract = {Functional impairment of dendritic cells (DC) appears to be one of the mechanisms responsible for tumor escape from the control of the immune system. DC isolated from tumor-bearing animals and cancer patients with solid or with hematological malignancies have phenotypic and functional abnormalities. In addition, supernatants from in vitro cultured tumor cells have been shown to interfere with DC differentiation from CD34+ and monocyte precursors. Primary effusion lymphoma (PEL) is a Human Herpesvirus-8 (HHV-8)-associated tumor, which releases several cytokines such as IL-6, IL-10 and VEGF and its growth seems to be dependent on them in vitro or in vivo. In the present study, we found that these cytokines released by PELs have also an important role in interfering with the in vitro differentiation of immature DC (iDC) from CD14+ monocytes. The iDC obtained in the presence of PEL supernatants showed reduction of FITC-dextran uptake, reduction of MLR allostimulatory activity and altered expression of surface molecules, suggesting that cytokines released by PEL adversely affect DC differentiation.}, } @article {pmid18678310, year = {2008}, author = {Yamano, T and Nakatani, S and Kanzaki, H and Toh, N and Amaki, M and Tanaka, J and Abe, H and Hasegawa, T and Sawada, T and Matsubara, H and Kitakaze, M}, title = {Exercise-induced changes of functional mitral regurgitation in asymptomatic or mildly symptomatic patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {102}, number = {4}, pages = {481-485}, doi = {10.1016/j.amjcard.2008.03.086}, pmid = {18678310}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology ; Echocardiography, Doppler, Color ; *Exercise ; Exercise Test ; *Exercise Tolerance ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Mitral Valve/*pathology ; Mitral Valve Insufficiency/diagnostic imaging/*etiology/physiopathology ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke Volume ; Systole ; Time Factors ; }, abstract = {It has remained unclear why functional mitral regurgitation (MR), even if it is of a mild degree, has prognostic importance in patients with idiopathic dilated cardiomyopathy (IDC). Exercise-induced changes in functional MR, which might be a clue to this question, have not been fully clarified. Thus, in this study, semisupine exercise echocardiography was performed on 32 asymptomatic or mildly symptomatic patients with IDC (29 men, mean age 45 +/- 14 years). The mean ejection fraction was 28 +/- 10% (range 13% to 45%). The effective regurgitant orifice (ERO) area of MR was measured, as well as echocardiographic parameters including mitral valve geometry. ERO at rest was associated best with systolic mitral tenting area (r(S) = 0.85, p <0.001). Functional MR did not newly appear during exercise in 9 subjects without MR at rest. In the remaining 23 subjects with functional MR at rest, all showed exacerbations of MR, with a median ERO of 10.5 mm(2) (interquartile range 6.3 to 16.5) to 18.7 mm(2) (interquartile range 9.5 to 29.3) (p <0.001). An increase in ERO was correlated best with the enlargement of tenting area (r(S) = 0.90, p <0.001) and was the strongest independent determinant of exercise duration (beta = -0.55, p = 0.002, multiple R(2) = 0.46). In conclusion, functional MR complicated with IDC was significantly exacerbated during exercise, with mitral valve deformation, which was strongly related to exercise intolerance; thus, the clinical impact of functional MR in patients with IDC could be more serious than can be expected by its degree at rest.}, } @article {pmid18677762, year = {2008}, author = {Monaco, SE and Dabbs, DJ and Kanbour-Shakir, A}, title = {Pleomorphic lobular carcinoma in pleural fluid: diagnostic pitfall for atypical mesothelial cells.}, journal = {Diagnostic cytopathology}, volume = {36}, number = {9}, pages = {657-661}, doi = {10.1002/dc.20866}, pmid = {18677762}, issn = {1097-0339}, mesh = {Biopsy ; Breast Neoplasms/complications/*diagnosis/*pathology ; Cadherins/metabolism ; Carcinoma, Lobular/complications/*diagnosis/*pathology ; *Diagnostic Errors ; Epithelium/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Pleural Effusion/complications/*pathology ; }, abstract = {Pleomorphic lobular carcinoma (PLC) is a subtype of infiltrating lobular carcinoma because of its dyscohesiveness, linear infiltration pattern, and lack of membranous E-cadherin staining. However, it differs from classic lobular carcinoma because of its high-grade cytology and more aggressive clinical behavior. In breast fine-needle aspiration biopsies, PLC can be confused with invasive ductal carcinoma, particularly the apocrine variant. In this report, we illustrate how metastatic PLC in body fluid specimens shows many of the same cytomorphologic changes that occur in reactive/atypical mesothelial cells. Fortunately, the immunohistochemical staining pattern of PLC can help to distinguish it from other possible diagnoses in the differential, such as reactive/atypical mesothelial cells and other metastatic neoplasms. However, the frequent apocrine features seen in this variant of breast carcinoma can cause nonspecific immunohistochemical positivity that may make the interpretation difficult. This is the first report illustrating the cytopathology and immunohistochemical findings of pleomorphic lobular carcinoma in body cavity fluid cytology. Our case highlights the important issues and pitfalls to be aware of when making this diagnosis.}, } @article {pmid18668643, year = {2008}, author = {Buchanan, CL and Flynn, LW and Murray, MP and Darvishian, F and Cranor, ML and Fey, JV and King, TA and Tan, LK and Sclafani, LM}, title = {Is pleomorphic lobular carcinoma really a distinct clinical entity?.}, journal = {Journal of surgical oncology}, volume = {98}, number = {5}, pages = {314-317}, doi = {10.1002/jso.21121}, pmid = {18668643}, issn = {1096-9098}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*pathology/therapy ; Carcinoma, Lobular/*pathology/therapy ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Attempts to define the clinical behavior of pleomorphic lobular carcinoma (PLC) have been limited to small series, and clinical management strategies have yet to be established. We describe our experience with PLC as compared to classic ILC and invasive ductal carcinoma (IDC).

METHODS: From 9/1996 to 5/2003, clinical and histopathologic data for 5,635 patients undergoing primary surgical treatment and sentinel lymph node biopsy for breast cancer were collected. Four hundred eighty one (8.5%) patients were diagnosed with ILC; 3,978 (70.6%) with IDC. Of those with ILC, 356 (74%) patients had material available for pathologic re-review and comprise our study population: 52 were classified as PLC; 298 were classified as classic ILC; and 6 cases were reclassified as IDC. We compared clinical, pathologic, and treatment factors for patients with PLC, ILC, and IDC using the Wilcoxon rank sum and Fisher's exact tests.

RESULTS: PLC were larger than ILC and IDC (20 vs. 15 vs. 13, P < 0.001), had more positive nodes (median 1 vs. 0 vs. 0, P < 0.05) and more frequently required mastectomy (63.5% vs. 38.7% vs. 28.8%, P < 0.001). In addition, more patients with PLC had developed metastatic disease compared to patients with ILC (11.5% vs. 3.7%, P < 0.05).

CONCLUSIONS: These findings suggest that PLC is a distinct clinical entity that presents at a more advanced stage and may require more aggressive surgical and adjuvant treatment.}, } @article {pmid18665173, year = {2008}, author = {McCarthy, PL and Mercer, FC and Savicky, MW and Carter, BA and Paterno, GD and Gillespie, LL}, title = {Changes in subcellular localisation of MI-ER1 alpha, a novel oestrogen receptor-alpha interacting protein, is associated with breast cancer progression.}, journal = {British journal of cancer}, volume = {99}, number = {4}, pages = {639-646}, pmid = {18665173}, issn = {1532-1827}, mesh = {Adult ; Aged ; Blotting, Western ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Cell Nucleus/*metabolism/pathology ; Cell Proliferation/drug effects ; Cells, Cultured ; Colony-Forming Units Assay ; Cytoplasm/metabolism/pathology ; DNA-Binding Proteins ; Disease Progression ; Doxycycline/pharmacology ; Estrogen Receptor alpha/*metabolism ; Estrogens/pharmacology ; Female ; Humans ; Immunoenzyme Techniques ; Immunoprecipitation ; Kidney/metabolism ; Middle Aged ; Nuclear Proteins/*metabolism ; Subcellular Fractions ; Tissue Array Analysis ; Transcription Factors/*metabolism ; }, abstract = {The oestrogen receptor-alpha (ER alpha) plays a key role in breast development and tumorigenesis and inhibiting its activity remains a prime strategy in the treatment of ER alpha-positive breast cancers. Thus, elucidation of the molecular mechanisms responsible for regulating ER alpha activity may facilitate the design of new, more effective breast cancer therapies. The MI-ER1 alpha is a novel transcriptional repressor that contains an LXXLL motif for interaction with nuclear hormone receptors. We investigated the ability of MI-ER1 alpha to bind to ER alpha in HEK293 and MCF-7 breast carcinoma cells, using co-immunoprecipitation assays. In both cell lines, MI-ER1 alpha interacted with ER alpha in the presence and absence of oestrogen, but the interaction was stronger in the absence of ligand. Functional analysis revealed that overexpression of MI-ER1 alpha in T47D breast carcinoma cells results in inhibition of oestrogen-stimulated anchorage-independent growth, suggesting that MI-ER1 alpha may play a role in regulating breast carcinoma cell proliferation in vivo. To explore this further, we performed an immunohistochemical analysis of normal breast tissue and breast carcinoma; a total of 110 cases were examined in whole tissue sections and 771 cases were analysed in tissue microarrays. No consistent difference in the MI-ER1 alpha expression level between normal breast tissue and breast carcinoma was discernible. However, there was a dramatic shift in the subcellular localisation: nuclear MI-ER1 alpha was detectable in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of DCIS, 25% of ILC and 4% of IDC contained nuclear staining. This shift from nuclear to cytoplasmic localisation of MI-ER1 alpha during breast cancer progression suggests that loss of nuclear MI-ER1 alpha might contribute to the development of invasive breast carcinoma.}, } @article {pmid18662704, year = {2008}, author = {Prasad, CP and Mirza, S and Sharma, G and Prashad, R and DattaGupta, S and Rath, G and Ralhan, R}, title = {Epigenetic alterations of CDH1 and APC genes: relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast.}, journal = {Life sciences}, volume = {83}, number = {9-10}, pages = {318-325}, doi = {10.1016/j.lfs.2008.06.019}, pmid = {18662704}, issn = {0024-3205}, mesh = {Adenomatous Polyposis Coli Protein/genetics/metabolism ; Antigens, CD ; Breast Neoplasms/*genetics/metabolism/pathology ; Cadherins/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cell Line, Tumor ; DNA Methylation ; *Epigenesis, Genetic ; Female ; *Genes, APC ; Humans ; Kaplan-Meier Estimate ; Prospective Studies ; *Signal Transduction ; Wnt Proteins/genetics/*metabolism ; beta Catenin/genetics/*metabolism ; }, abstract = {Activation of canonical Wnt/beta-catenin pathway in Invasive Ductal Carcinoma of Breast (IDCs) was recently reported from our laboratory. Herein, we analyzed promoter methylation status of CDH1 and Adenomatous polyposis coli (APC) genes in 50 IDCs and correlated with expression of E-cadherin (E-CD) and APC proteins and with activation of oncogenic Wnt/beta-catenin signaling pathway components, Dvl, beta-catenin and CyclinD1. Further, Wnt/beta-catenin driven epithelial mesenchymal transition (EMT) was investigated by correlating the expression of Dvl, beta-catenin and CyclinD1 with vimentin expression in these IDCs. Promoter hypermethylation was observed in 25/50 (50%) IDCs for CDH1 and in 11/50 (22%) tumors for APC, associated with loss of expression of E-CD and APC proteins; concordant hypermethylation of these genes was observed in paired patients' sera. Further, 57% of tumors harboring CDH1 methylation and 50% tumors harboring the methylated APC gene showed nuclear localization of beta-catenin, suggesting activation of the canonical Wnt/beta-catenin pathway. Our study demonstrates significant association between vimentin expression and nuclear beta-catenin (p=0.001; Odds ratio (OR)=25.6) and Dvl (p=0.023; OR=8.0), suggesting that EMT may be driven by Wnt/beta-catenin activation in IDCs. In conclusion, we demonstrate correlation of CDH1 and APC promoter methylation with loss of E-CD and APC proteins and with activation of Wnt/beta-catenin signaling pathway. Association of nuclear Dvl and beta-catenin with vimentin expression suggests the importance of Wnt/beta-catenin pathway driven EMT in IDCs. The concordance between CDH1 and APC methylation in IDCs and paired circulating DNA underscores the utility of serum DNA as a non-invasive tool for methylation analysis in IDC patients.}, } @article {pmid18660445, year = {2008}, author = {Jerosch-Herold, M and Sheridan, DC and Kushner, JD and Nauman, D and Burgess, D and Dutton, D and Alharethi, R and Li, D and Hershberger, RE}, title = {Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {295}, number = {3}, pages = {H1234-H1242}, pmid = {18660445}, issn = {0363-6135}, support = {5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01-HL-58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Cardiomyopathy, Dilated/genetics/metabolism/*pathology ; Computer Simulation ; Contrast Media/metabolism ; Coronary Circulation/*physiology ; Extracellular Space/metabolism ; Female ; Gadolinium DTPA/pharmacokinetics ; Heart/*physiology ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Models, Statistical ; Mutation/genetics ; Myocardium/metabolism/*pathology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium. CMR was performed in nine persons affected with IDC/FDC. Healthy controls came from the general population (n = 6) or were unaffected family members of FDC patients (n = 3) without signs or symptoms of IDC/FDC or any structural cardiac abnormalities. The myocardial partition coefficient for gadolinium contrast (lambda(Gd)) was determined by T1 measurements. LV shape and function and MBF were assessed by standard CMR methods. lambda(Gd) was elevated in IDC/FDC patients vs. healthy controls (lambda(Gd) = 0.56 +/- 0.15 vs. 0.41 +/- 0.06; P = 0.002), and correlated with LV enlargement (r = 0.61 for lambda(Gd) vs. end-diastolic volume indexed by height; P < 0.01) and with ejection fraction (r = -0.80; P < 0.001). The extracellular volume fraction was higher in IDC patients than in healthy controls (0.31 +/- 0.05 vs. 0.24 +/- 0.03; P = 0.002). Resting MBF was lower in IDC patients (0.64 +/- 0.13 vs. 0.91 +/- 0.22; P = 0.01) than unaffected controls and correlated with both the partition coefficient (r = -0.57; P = 0.012) and the extracellular volume fraction (r = -0.56; P = 0.019). The expansion of the extracellular space correlated with reduced MBF and ventricular dilation. Expansion of the extracellular matrix may be a key contributor to contractile dysfunction in IDC patients.}, } @article {pmid18650623, year = {2008}, author = {Gutierrez, JC and Hurley, JD and Housri, N and Perez, EA and Byrne, MM and Koniaris, LG}, title = {Are many community hospitals undertreating breast cancer?: lessons from 24,834 patients.}, journal = {Annals of surgery}, volume = {248}, number = {2}, pages = {154-162}, doi = {10.1097/SLA.0b013e31816c4030}, pmid = {18650623}, issn = {1528-1140}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/pathology/*therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Florida ; Health Care Surveys ; Hospitals, Community/*statistics & numerical data ; Hospitals, University/*statistics & numerical data ; Humans ; Immunohistochemistry ; Mastectomy/methods ; Middle Aged ; Neoplasm Staging ; Outcome Assessment, Health Care/*statistics & numerical data ; Practice Patterns, Physicians'/*statistics & numerical data ; Radiotherapy, Adjuvant ; Registries ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {OBJECTIVE: To compare treatment patterns and long-term outcomes between teaching and community hospitals treating patients with infiltrating ductal carcinoma (IDC).

METHODS: All IDCs from the Florida Cancer Data System from 1994 to 2000 were examined.

RESULTS: Overall, 24,834 operative cases of IDC were identified. Teaching hospitals treated 11.3% of patients with a larger proportion of stage III and IV disease (39.8% vs. 33.0%). Five- and 10-year overall survival rates at teaching hospitals were 84% and 72%, compared with 81% and 69% at high-volume community hospitals and 77% and 63% at low-volume hospitals (P < 0.001). The greatest differences on survival were observed in patients with advanced IDC. Examination of practice patterns demonstrated that multimodality therapy was most frequently administered in teaching hospitals. Breast-conserving surgery was more frequently performed at teaching hospitals (41.5% vs. 38.9% P = 0.008). On multivariate analysis, it was found that treatment at a teaching hospital was a significant independent predictor of improved survival (hazard ratio = 0.763, P < 0.001). This survival benefit was greater and independent of high-volume center status (hazard ratio = 0.903, P < 0.02).

CONCLUSIONS: Patients with IDC treated at teaching hospitals have significantly better survival than those treated at high-volume centers or community hospitals, particularly in the setting of advanced disease. Poorer long-term outcomes for IDC at community hospitals seem to be, at least in part, because of decreased use of proven life-extending adjuvant therapies. These results should encourage community hospitals to institute changes in treatment approaches to invasive breast cancer to optimize patient outcomes.}, } @article {pmid18650160, year = {2008}, author = {Anavekar, NS and Rozen, WM and Rowe, K and Murphy, C}, title = {Synchronous carcinoma and lymphoma of the breast.}, journal = {Clinical breast cancer}, volume = {8}, number = {3}, pages = {281-284}, doi = {10.3816/CBC.2008.n.033}, pmid = {18650160}, issn = {1526-8209}, mesh = {Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Female ; Humans ; Lymphoma, B-Cell/*pathology ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {Primary breast lymphoma is a rare entity. Furthermore, extranodal marginal zone B-cell lymphoma affecting the breast is exceedingly rare. We report a unique case of invasive lobular carcinoma diagnosed simultaneously with an extranodal marginal zone B-cell lymphoma of the breast. A literature review demonstrated 2 reports of synchronous invasive ductal carcinoma and mucosa-associated lymphoid tissue lymphoma affecting the breast; however, there is a paucity of cases demonstrating different malignancies affecting the same breast tissue in a particular patient, especially in the setting of lobular carcinoma. As such, there are no clear guidelines on the optimal management of such synchronous tumors. Herein, the diagnostic and management issues are explored.}, } @article {pmid18643929, year = {2008}, author = {Zhou, X and Coad, J and Ducatman, B and Agazie, YM}, title = {SHP2 is up-regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis.}, journal = {Histopathology}, volume = {53}, number = {4}, pages = {389-402}, doi = {10.1111/j.1365-2559.2008.03103.x}, pmid = {18643929}, issn = {1365-2559}, support = {R01 CA124940/CA/NCI NIH HHS/United States ; 2P20RR016440/RR/NCRR NIH HHS/United States ; CA124940/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*enzymology/genetics ; Carcinoma, Ductal, Breast/*enzymology/genetics/metabolism ; Cell Transformation, Neoplastic/genetics/metabolism ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/*metabolism ; Tumor Cells, Cultured ; *Up-Regulation ; }, abstract = {AIMS: To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up-regulated in breast cancer and, if so, to determine whether its up-regulation has any relationship with clinical variables of breast cancer.

METHODS AND RESULTS: Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant-negative expression and anchorage-independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant-negative SHP2 blocked anchorage-independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients.

CONCLUSION: SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2's positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.}, } @article {pmid18638597, year = {2008}, author = {Friedberg, MK and Slorach, C}, title = {Relation between left ventricular regional radial function and radial wall motion abnormalities using two-dimensional speckle tracking in children with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {102}, number = {3}, pages = {335-339}, doi = {10.1016/j.amjcard.2008.03.064}, pmid = {18638597}, issn = {0002-9149}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*physiopathology ; Child ; Child, Preschool ; Echocardiography/*methods ; Female ; Heart Ventricles/*physiopathology ; Humans ; Infant ; Infant, Newborn ; Male ; Stroke Volume/physiology ; }, abstract = {Left ventricular (LV) regional radial function and its relation to radial wall motion abnormalities have not been investigated in children with idiopathic dilated cardiomyopathy (IDC). Radial strain was measured using 2-dimensional speckle tracking to evaluate regional radial function and wall motion in 6 LV segments in 24 children (0 to 18 years old) with IDC and 16 healthy controls. Patients and controls were similar in age. Patients with IDC had higher heart rates (97 +/- 28 vs 77 +/- 19, p <0.05) and decreased ejection fraction (34 +/- 12% vs 66 +/- 7%, p <0.0001) compared with controls. Radial strain in all segments was significantly lower in patients with IDC. In IDC, average radial strain correlated well with ejection fraction (r = 0.8, p <0.0001). The SD of time to peak radial strain among 6 LV segments was significantly higher in patients with IDC than in controls (56 +/- 38 vs 15 +/- 12 ms, p <0.0001). Segmental peak radial strain correlated closely to time to peak radial strain in controls (r = 0.98, p = 0.0008), but less in patients with IDC (r = 0.76, p = 0.07). In conclusion, LV regional radial function is impaired in pediatric IDC, in association with increased radial dyssynchrony, revealing a possible important mechanism for LV dysfunction in these children.}, } @article {pmid18636275, year = {2009}, author = {Xuan, Y and Lin, Z}, title = {Expression of Indian Hedgehog signaling molecules in breast cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {135}, number = {2}, pages = {235-240}, pmid = {18636275}, issn = {1432-1335}, mesh = {Adult ; Aged, 80 and over ; Breast/cytology/*physiology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Disease Progression ; Female ; Hedgehog Proteins/genetics/*physiology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Middle Aged ; Neoplasm Invasiveness ; Patched Receptors ; Patched-1 Receptor ; Receptors, Cell Surface/genetics ; Receptors, Estrogen/analysis ; Receptors, G-Protein-Coupled/genetics ; Receptors, Progesterone/analysis ; Smoothened Receptor ; }, abstract = {PURPOSE: To investigate the clinicopathological significance and expression pattern of Hedgehog (Hh) signaling molecules in breast normal glands and invasive ductal carcinoma.

MATERIALS AND METHODS: A total of 142 cases, including 21 of normal breast and 121 of invasive ductal carcinoma of the breast, were immunohistochemically analyzed for Ihh, Ptch, Smo, Gli-1, Gli-2, and Gli-3 protein expression.

RESULTS: All of Hh signaling molecules were greatly enhanced in invasive ductal carcinoma compared with the normal breast epithelia. The expressions of Ihh, Smo, and Gli-2 were increased in PR negative cases, and the expressions of Ihh, Ptch, and Gli-1/2/3 were statistically correlated with increased proliferating index of Ki-67 in invasive ductal carcinoma. Ihh and Gli-1/2/3 expressions were correlated with node metastasis. Additionally, the protein expressions of Ihh, Ptch, and Gli-2 were correlated with the clinical stage of breast cancer.

CONCLUSIONS: Hedgehog signaling molecules play an important role in the progression of invasive ductal carcinoma of breast.}, } @article {pmid18633230, year = {2008}, author = {Yoshibayashi, H and Ishiguro, H and Takada, M and Takeuchi, M and Yamashiro, H and Ueno, T and Kato, H and Yoshikawa, K and Kanao, S and Yamauchi, C and Mikami, Y and Toi, M}, title = {[A case of primary breast cancer who responded remarkably to the neoadjuvant chemotherapy with the combination of docetaxel and cyclophosphamide].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {35}, number = {6}, pages = {987-990}, pmid = {18633230}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Cyclophosphamide/*therapeutic use ; Docetaxel ; Female ; Humans ; Magnetic Resonance Imaging ; *Neoadjuvant Therapy ; Taxoids/*therapeutic use ; }, abstract = {A 67-year-old woman visited our hospital with suspicion of right breast cancer. She underwent core needle biopsy, and her disease was diagnosed as breast cancer (invasive ductal carcinoma, ER- and PgR- positive, HER2-negative). We chose neoadjuvant chemotherapy, because the tumor size was over 3 cm in diameter and she wished to conserve her breast. She was elderly, and so without anthracycline base, we used a combination of docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) q3w 6 cycles followed by breast-conserving therapy. During treatment, the patient remained very well and showed no major side effects except grade 4 neutropenia on an outpatient basis. After 6 cycles, ultrasonography and mammography indicated the residual tumor, but breast MRI did not detect any tumor. Pathological examination showed absence of invasive tumor or only focal residual tumor cells (QpCR). We concluded that the combination of docetaxel and cyclophosphamide was a good option for neoadjuvant chemotherapy for early breast cancer.}, } @article {pmid18628458, year = {2008}, author = {Iakovlev, VV and Arneson, NC and Wong, V and Wang, C and Leung, S and Iakovleva, G and Warren, K and Pintilie, M and Done, SJ}, title = {Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {14}, number = {14}, pages = {4446-4454}, doi = {10.1158/1078-0432.CCR-07-4960}, pmid = {18628458}, issn = {1078-0432}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosomes, Human, Pair 17/*genetics ; Female ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {PURPOSE: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis.

EXPERIMENTAL DESIGN: Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes.

RESULTS: Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).

CONCLUSIONS: Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.}, } @article {pmid18612038, year = {2008}, author = {Tykocinski, OE}, title = {Insurance, risk, and magical thinking.}, journal = {Personality & social psychology bulletin}, volume = {34}, number = {10}, pages = {1346-1356}, doi = {10.1177/0146167208320556}, pmid = {18612038}, issn = {0146-1672}, mesh = {Accidents, Traffic/economics/psychology/statistics & numerical data ; Adult ; Female ; Health Services Accessibility ; Humans ; Insurance/economics/*statistics & numerical data ; Insurance Coverage/statistics & numerical data ; Insurance Selection Bias ; Insurance, Health ; *Intuition ; Judgment ; *Magic ; Male ; Medically Uninsured/psychology ; Mental Disorders ; Middle Aged ; Models, Psychological ; Probability ; Risk ; *Risk Assessment ; Risk Factors ; Travel ; Volition ; }, abstract = {The possession of an insurance policy may not only affect the severity of a potential loss but also its perceived probability. Intuitively, people may feel that if they are insured nothing bad is likely to happen, but if they do not have insurance they are at greater peril. In Experiment 1, respondents who were reminded of their medical insurance felt they were less likely to suffer health problems in the future compared to people who were not reminded of their medical insurance. In Experiment 2a, participants who were unable to purchase travel insurance judged the probability of travel-related calamities higher compared to those who were insured. These results were replicated in Experiment 3a in a simulation of car accident insurance. The findings are explained in terms of intuitive magical thinking, specifically, the negative affective consequences of "tempting fate" and the sense of safety afforded by the notion of "being covered."}, } @article {pmid18611928, year = {2010}, author = {Wei, J and Cui, L and Liu, F and Fan, Y and Lang, R and Gu, F and Guo, X and Tang, P and Fu, L}, title = {E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast.}, journal = {International journal of surgical pathology}, volume = {18}, number = {3}, pages = {193-200}, doi = {10.1177/1066896908320832}, pmid = {18611928}, issn = {1940-2465}, mesh = {Adenocarcinoma, Papillary/blood supply/metabolism/*secondary ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/*secondary ; Cell Polarity ; E-Selectin/*metabolism ; Female ; Humans ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Microvessels/pathology ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Sialyl Lewis X Antigen ; }, abstract = {To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin-positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.}, } @article {pmid18593679, year = {2008}, author = {Wilson, NM and Espirito, JL and Valero, V and Pusztai, L}, title = {Paclitaxel-induced sickle cell crisis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {65}, number = {14}, pages = {1333-1336}, doi = {10.2146/ajhp070432}, pmid = {18593679}, issn = {1535-2900}, mesh = {Black or African American ; *Anemia, Sickle Cell ; Antineoplastic Agents, Phytogenic/administration & dosage/*adverse effects/pharmacology ; Breast Neoplasms/drug therapy ; Female ; Humans ; Middle Aged ; Paclitaxel/administration & dosage/*adverse effects/pharmacology ; Pain/*chemically induced ; }, abstract = {PURPOSE: A case of paclitaxel-induced painful crisis in a patient with breast cancer and hemoglobin sickle cell disease (SCD) is reported.

SUMMARY: A 55-year-old postmenopausal African-American woman had stage IIB invasive ductal carcinoma of the left breast. She was not taking any medications and did not report a history of cancer or other diseases. She had mild microcytic anemia, but the rest of her blood counts and liver function test values were normal. Bone scans and computed tomography scans of her chest and abdomen did not reveal any metastatic disease. She underwent a routine left segmental mastectomy and axillary lymph node dissection that revealed a 4-cm invasive cancer with 1 of 10 axillary lymph nodes positive for metastatic disease. Her treatment plan included chemotherapy with weekly paclitaxel, followed by fluorouracil, epirubicin, and cyclophosphamide and radiation. The first cycle of paclitaxel was well tolerated until one week after initiation when the patient woke up in the middle of the night with a sudden onset of excruciating back pain and muscle spasms. Other symptoms that developed included fatigue, left-sided rib pain, and shortness of breath. The patient recalled being told that she had sickle cell trait but said that she never had a sickle cell crisis. Laboratory tests during her 13-day hospitalization revealed hemolysis. The patient was diagnosed with hemoglobin SCD and later discharged with as-needed, low-dose oxycodone and baclofen, antibiotics, and folic acid.

CONCLUSION: A patient with breast cancer and SCD had a painful crisis after receiving paclitaxel as part of her chemotherapy regimen.}, } @article {pmid18592167, year = {2008}, author = {Kuroda, N and Fujishima, N and Inoue, K and Ohara, M and Hirouchi, T and Mizuno, K and Hayashi, Y and Lee, GH}, title = {Basal-like carcinoma of the breast: further evidence of the possibility that most metaplastic carcinomas may be actually basal-like carcinomas.}, journal = {Medical molecular morphology}, volume = {41}, number = {2}, pages = {117-120}, pmid = {18592167}, issn = {1860-1480}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Basal Cell/*pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/secondary ; Middle Aged ; Neoplasm Metastasis/*pathology ; }, abstract = {Some investigators have previously suggested that basal-like carcinoma may consist of components of invasive ductal carcinoma, not otherwise specified, metaplastic carcinoma, and medullary carcinoma. We report here two cases of breast carcinoma showing basal cell/myoepithelial differentiation. The first case was a 58-year-old Japanese woman and the second case was a 39-year-old Japanese woman. The two tumors were composed of the proliferation of epithelial cells and/or spindle-or stellate-shaped cells on the background of mucinous materials. Additionally, chondroid matrix was observed in the metastatic lesion of the first case and the primary lesion of the second case. Immunohistochemically, epithelial neoplastic cells were positive for E-cadherin and cytokeratin CAM5.2, and epithelial and spindle-or stellate-shaped cells were positive for cytokeratins 5, 14, or 17, alpha-smooth muscle actin, S-100, and p63. Our results supply further evidence that most metaplastic carcinomas may be actually be basallike carcinomas.}, } @article {pmid19960117, year = {2008}, author = {Crits-Christoph, P and Gibbons, MB and Gallop, R and Ring-Kurtz, S and Barber, JP and Worley, M and Present, J and Hearon, B}, title = {Supportive-Expressive Psychodynamic Therapy for Cocaine Dependence: A Closer Look.}, journal = {Psychoanalytic psychology : the official journal of the Division of Psychoanalysis, American Psychological Association, Division 39}, volume = {25}, number = {3}, pages = {483-498}, pmid = {19960117}, issn = {0736-9735}, support = {U18 DA007090/DA/NIDA NIH HHS/United States ; K01 MH063149/MH/NIMH NIH HHS/United States ; R01 DA018935/DA/NIDA NIH HHS/United States ; R24 MH070698/MH/NIMH NIH HHS/United States ; R01 DA018935-01/DA/NIDA NIH HHS/United States ; }, abstract = {Using data from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, this article focuses on the outcomes of patients who received supportive-expressive (SE) psychodynamically-oriented psychotherapy (plus group drug counseling; GDC). Short-term SE for cocaine dependent individuals, while not the most efficacious treatment examined in the study (individual drug counseling [IDC] plus GDC was), produced large improvements in cocaine use. In addition, there was evidence that SE was superior to IDC on change in family/social problems at the 12 month follow-up assessment, particularly for those patients with relatively more severe difficulties in this domain at baseline. For patients who achieved abstinence early in treatment, SE produced comparable drug use outcomes to IDC, with mean drug use scores numerically lower for SE at all of the follow-up assessments (9, 12, 15, and 18 months). SE patients who achieved initial abstinence decreased cocaine use from a mean 10.1 days per month at baseline to a mean of 1.3 days at 12 months.}, } @article {pmid18585512, year = {2008}, author = {Parks, SB and Kushner, JD and Nauman, D and Burgess, D and Ludwigsen, S and Peterson, A and Li, D and Jakobs, P and Litt, M and Porter, CB and Rahko, PS and Hershberger, RE}, title = {Lamin A/C mutation analysis in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.}, journal = {American heart journal}, volume = {156}, number = {1}, pages = {161-169}, pmid = {18585512}, issn = {1097-6744}, support = {R01 HL058626-08/HL/NHLBI NIH HHS/United States ; 5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01 HL058626/HL/NHLBI NIH HHS/United States ; M01 RR000334/RR/NCRR NIH HHS/United States ; R01- HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Cardiomyopathy, Dilated/epidemiology/*genetics/pathology ; Cohort Studies ; DNA Mutational Analysis ; Female ; Gene Expression Regulation ; Genetic Predisposition to Disease/*epidemiology ; *Heterozygote ; Humans ; Lamin Type A/genetics ; Male ; Middle Aged ; *Mutation, Missense ; Nuclear Lamina/genetics ; Pedigree ; Polymerase Chain Reaction ; Prognosis ; Severity of Illness Index ; Survival Analysis ; }, abstract = {BACKGROUND: Lamin A/C mutations are a well-established cause of dilated cardiomyopathy (DCM), although their frequency has not been examined in a large cohort of patients. We sought to examine the frequency of mutations in LMNA, the gene encoding lamin A/C, in patients with idiopathic (IDC) or familial dilated cardiomyopathy (FDC).

METHODS: Clinical cardiovascular data, family histories, and blood samples were collected from 324 unrelated IDC probands, of whom 187 had FDC. DNA samples were sequenced for nucleotide alterations in LMNA. Likely protein-altering mutations were followed up by evaluating additional family members, when possible.

RESULTS: We identified 18 protein-altering LMNA variants in 19 probands or 5.9% of all cases (7.5% of FDC; 3.6% of IDC). Of the 18 alterations, 11 were missense (one present in 2 kindreds), 3 were nonsense, 3 were insertion/deletions, and 1 was a splice site alteration. Conduction system disease and DCM were common in carriers of LMNA variants. Unexpectedly, in 6 of the 19 kindreds with a protein-altering LMNA variant (32%), at least one affected family member was negative for the LMNA variant.

CONCLUSIONS: Lamin A/C variants were observed with a frequency of 5.9% in probands with DCM. The novel observation of FDC pedigrees in which not all affected individuals carry the putative disease-causing LMNA mutation suggests that some protein-altering LMNA variants are not causative or that some proportion of FDC may be because of multiple causative factors. These findings warrant increased caution in FDC research and molecular diagnostics.}, } @article {pmid18584413, year = {2008}, author = {Schubert, A and Schulz, H and Emons, G and Gründker, C}, title = {Expression of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in HCC70 breast cancer cells and effects of treatment with gonadotropin-releasing hormone on RANKL expression.}, journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology}, volume = {24}, number = {6}, pages = {331-338}, doi = {10.1080/09513590802095845}, pmid = {18584413}, issn = {1473-0766}, mesh = {Antineoplastic Agents, Hormonal/*pharmacology ; Blotting, Western ; Breast Neoplasms/*drug therapy/genetics/*metabolism ; Cell Line, Tumor ; Coculture Techniques ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Immunohistochemistry ; Osteoblasts/cytology/metabolism ; Osteoprotegerin/*biosynthesis/genetics ; RANK Ligand/*biosynthesis/genetics ; RNA, Messenger/biosynthesis/genetics ; Receptors, LHRH/biosynthesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Triptorelin Pamoate/*pharmacology ; }, abstract = {BACKGROUND: The majority of human breast cancers and in addition most breast-cancer cell lines express gonadotropin-releasing hormone (GnRH) receptors. Their proliferation and in addition their bone-directed invasion is time- and dose-dependently reduced by GnRH. Osteolytic metastases are characteristic for breast cancer-derived metastasis. Since the osteolytic activity depends on the receptor activator of nuclear factor-kappaB (NFkappaB) ligand (RANKL)/osteoprotegerin (OPG) ratio, we analyzed RANKL and OPG expression in different breast-cancer cell lines.

METHODS: Different human breast-cancer cell lines were tested for expression of GnRH receptor, OPG and RANKL. Using a co-culture system of breast-cancer cell lines and human primary osteoblasts (hOB), we analyzed the expression of OPG and RANKL in the GnRH receptor-positive breast-cancer cell line HCC70 co-cultured with or without hOB. In addition, we assessed the effects of GnRH analog treatment on OPG and RANKL mRNA and protein levels.

RESULTS: All tested breast-cancer cell lines were GnRH receptor-positive. The majority of these cell lines expressed OPG but not RANKL. The HCC70 breast-cancer cell line derived from an invasive ductal carcinoma with metastases was positive for both OPG and RANKL. The expression of RANKL by HCC70 cells was increased when co-cultured with hOB. Treatment with GnRH analogs reduced the expression of RANKL by HCC70 cells co-cultured with hOB. No effects were observed on breast cancer OPG expression.

CONCLUSIONS: These data show that the majority of human breast-cancer cell lines express OPG but not RANKL. The HCC70 breast-cancer cell line is RANKL-positive. Co-culture of HCC70 breast cancer cells with hOB increases RANKL expression. Activation of tumor GnRH receptors reduces RANKL expression. These experiments demonstrate that HCC70 breast cancer cells are able to activate osteoclasts directly via RANKL. The interaction between HCC70 breast cancer cells and osteoblasts induces osteoclastogenesis through an increase of RANKL expression. GnRH seems to play an important role by modulating the RANKL expression in HCC70 breast cancer cells.}, } @article {pmid18580238, year = {2008}, author = {Borkar, S and Pandit-Taskar, N}, title = {F-18 FDG uptake in cutaneous metastases from breast cancer.}, journal = {Clinical nuclear medicine}, volume = {33}, number = {7}, pages = {488-489}, doi = {10.1097/RLU.0b013e318177934e}, pmid = {18580238}, issn = {1536-0229}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*complications/*diagnostic imaging ; Diagnostic Imaging/methods ; Female ; Fluorodeoxyglucose F18/*pharmacokinetics ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/*pharmacokinetics ; Skin Neoplasms/*diagnostic imaging/*secondary ; }, abstract = {Cutaneous metastases from internal malignancies are rare with a reported incidence between 0.7% and 10%. Among all malignancies the highest incidence of cutaneous metastasis is seen in breast cancer. We report the detection of distant dermal metastases from breast cancer on F-18 FDG PET imaging. A 73-year-old woman with metastatic left breast cancer was referred for F-18 FDG PET/CT scan, which showed multiple FDG avid lesions along cutaneous and subcutaneous nodules in the posterior neck, bilateral proximal arms, anterior chest wall, and trunk. A punch biopsy of a right lower chest wall lesion revealed invasive ductal carcinoma involving the deep dermis.}, } @article {pmid18577507, year = {2008}, author = {Birnbaum, GE and Svitelman, N and Bar-Shalom, A and Porat, O}, title = {The thin line between reality and imagination: attachment orientations and the effects of relationship threats on sexual fantasies.}, journal = {Personality & social psychology bulletin}, volume = {34}, number = {9}, pages = {1185-1199}, doi = {10.1177/0146167208319692}, pmid = {18577507}, issn = {0146-1672}, mesh = {Adult ; *Courtship ; *Fantasy ; Female ; Hostility ; Humans ; *Imagination ; Male ; *Object Attachment ; Personality Inventory ; Psychological Distance ; *Reality Testing ; Sex Factors ; *Sexual Behavior ; Social Alienation/psychology ; Spouses/*psychology ; Young Adult ; }, abstract = {The authors examined the effects of relationship threats on sexual fantasies. In two studies, participants described a sexual fantasy following an imagination task and reported their attachment orientations. In Study 1, participants imagined relationship or nonrelationship threat scenes. Results indicated that relationship threat led to fantasies that involved interpersonal distance and hostility themes. Furthermore, following relational threat, women and more anxiously attached individuals were most likely to use relationship-maintaining strategies in their fantasies. More anxiously attached individuals were also particularly likely to represent themselves as alienated. In Study 2, participants imagined sexual or emotional threat scenes. The findings showed that sexual threat elicited self-enhancement, whereas emotional threat led to fantasies involving both self-enhancement and attachment-related themes. Emotional threat was also most likely to induce negative views of others in more avoidant women. Implications for understanding the underlying functions of sexual fantasies within the context of romantic relationships are discussed.}, } @article {pmid18575275, year = {2008}, author = {Miller-Graziano, CL and De, A and Laudanski, K and Herrmann, T and Bandyopadhyay, S}, title = {HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function.}, journal = {Novartis Foundation symposium}, volume = {291}, number = {}, pages = {196-208; discussion 208-11, 221-4}, doi = {10.1002/9780470754030.ch15}, pmid = {18575275}, issn = {1528-2511}, support = {R01-GM036214/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Inflammatory Agents/*pharmacology ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Dendritic Cells/cytology/drug effects/immunology ; Heat-Shock Proteins/*pharmacology ; Humans ; Immunity/*drug effects ; Immunologic Factors/*pharmacology ; Macrophages/cytology/drug effects/immunology ; Monocytes/cytology/drug effects/immunology ; Phagocytosis/drug effects ; Phenotype ; T-Lymphocytes/cytology/drug effects/immunology ; Thrombospondin 1/immunology ; }, abstract = {The effects of HSP27 on human monocytes (MO) are predominantly antiinflammatory through preferential interleukin (IL)10 induction and by alteration of MO to immature dendritic cells (iDCs) or MO to macrophage (Mac) differentiation. Initial HSP27 inclusion in IL4+GM-CSF MO to iDC induction cultures allows Mac differentiation (CD14++, CD16+), decreases iDC (CD1a+) differentiation, and depresses DC induction of allogeneic T lymphocyte proliferation (MLR). HSP27 increased MO IL10 and M-CSF production but subsequent increased Mac differentiation isn't responsible for depressed MO to iDC differentiation and function. Mac function after IL10 induced MO to Mac differentiation is also altered by HSP27 inclusion so that Mac phagocytic activity and scavenger receptor expression (CD163) are depressed. HSP27, in addition to immature DCs, doesn't increase Mac differentiation but instead generates inhibitory DCs, which depress rather than stimulate T cell proliferation even during anti CD3+CD28 induction. Upon maturation, these HSP27-altered inhibitory DCs have increased production of the T cell and DC suppressive mediator, thrombospondin 1. HSP27's anti-inflammatory and immunodepressive effects include deranging MO differentiation to both Mac and DCs, altering their receptor expression, and inducing production of inhibitory mediators such as thrombospondin-1 as well as IL10. These data suggest HSP27 belongs to a new group of 'anti-danger signals'.}, } @article {pmid18568671, year = {2008}, author = {Talley, L and Chhieng, DC and Bell, WC and Grizzle, WE and Frost, AR}, title = {Immunohistochemical detection of EGFR, p185(erbB-2), Bcl-2 and p53 in breast carcinomas in pre-menopausal and post-menopausal women.}, journal = {Biotechnic & histochemistry : official publication of the Biological Stain Commission}, volume = {83}, number = {1}, pages = {5-14}, doi = {10.1080/10520290701822436}, pmid = {18568671}, issn = {1473-7760}, support = {5-R25-CA47888-13/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/diagnosis/*metabolism ; ErbB Receptors/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins/analysis ; Postmenopause/*metabolism ; Premenopause/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {Young pre-menopausal women with breast carcinomas have an overall worse prognosis than older, post-menopausal women. Because histologic grade is a major predictor of tumor behavior and correlates with biomarker expression, we assessed the immunohistochemical expression of epidermal growth factor receptor (EGFR), p185(erbB-2) and Bcl-2, and nuclear accumulation of p53 in breast carcinomas in pre- and post-menopausal women with equivalent histologic grades. This allowed identification of differences in biomarker expression and prognostic significance in pre- and post-menopausal women independent of histologic grade. We investigated 100 infiltrating ductal carcinomas (IDC) in pre-menopausal women, ages 45 years and younger, and 100 IDC in post-menopausal women, ages 65 years and older. The IDC were selected so that the proportions of high and low/moderate grade carcinomas were equal in the pre- and post-menopausal groups. Prognostic utility of biomarker expression in pre- and post-menopausal groups was determined by product limit and multivariate analysis of survival. There were statistically significant differences in cytoplasmic expression of EGFR and Bcl-2 and nuclear accumulation of p53, but not in the expression of p185(erbB-2), in carcinomas of high vs. low histologic grade. There was no difference in the expression of EGFR, p185(erbB-2) or Bcl-2, or in nuclear accumulation of p53 in these IDC from pre- vs. post-menopausal women. Bcl-2 and the nuclear accumulation of p53 were of prognostic significance in our overall study population; however, when assessing pre- and post-menopausal women separately, Bcl-2 and p53 were of prognostic significance only in pre-menopausal, but not post-menopausal women. In summary expression of EGFR and Bcl-2 and nuclear accumulation of p53 were significantly associated with histologic grade, but not with menopausal status. In addition, there were differences in the prognostic effectiveness of these biomarkers in pre- vs. post-menopausal women.}, } @article {pmid18564057, year = {2009}, author = {Othman, MI and Majid, MI and Singh, M and Subathra, S and Seng, L and Gam, LH}, title = {Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients.}, journal = {Biotechnology and applied biochemistry}, volume = {52}, number = {Pt 3}, pages = {209-219}, doi = {10.1042/BA20070271}, pmid = {18564057}, issn = {1470-8744}, mesh = {Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; China ; Chromatography, Liquid ; Electrophoresis, Polyacrylamide Gel ; Female ; Gene Expression ; Humans ; Malaysia ; Neoplasm Proteins/*analysis ; *Proteomics ; Tandem Mass Spectrometry ; }, abstract = {Breast cancer is the leading cause of cancer-related mortality and morbidity among women worldwide and IDC (infiltrating ductal carcinoma) is the most common type of invasive breast cancer. The changes in the biological behaviour of cancer tissue can be predicted by measuring the differential protein expression of normal and cancerous tissues. Using a combination of SDS/PAGE and LC (liquid chromatography)-MS/MS (tandem MS), we identified 82 common and differentially expressed proteins from normal and cancerous breast tissues in 20 Malaysian Chinese patients with IDC. These proteins are extracted from the normal and cancerous tissue of patients and therefore represent the actual proteins involved in cancer development. Proteins identified possibly have significant roles in the development of breast cancer in Malaysian Chinese patients in view of their consistent expression in most of the patients, although some of the proteins had not been detected in earlier studies that were mostly carried out in Western countries. This observation suggests that molecular mechanisms leading to breast cancer development in this region may not be identical with those leading to IDC in Western regions.}, } @article {pmid18548321, year = {2009}, author = {Hayashi, H and Kimura, M and Yoshimoto, N and Tsuzuki, M and Tsunoda, N and Fujita, T and Yamashita, T and Iwata, H}, title = {A case of HER2-positive male breast cancer with lung metastases showing a good response to trastuzumab and paclitaxel treatment.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {16}, number = {2}, pages = {136-140}, doi = {10.1007/s12282-008-0060-1}, pmid = {18548321}, issn = {1880-4233}, mesh = {Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms, Male/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/*drug therapy/metabolism/secondary ; Male ; Paclitaxel/administration & dosage ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tomography, X-Ray Computed ; Trastuzumab ; Treatment Outcome ; }, abstract = {We present a case of advanced HER2-positive male breast cancer, which showed a good response to a combined treatment of trastuzumab and paclitaxel. A 78-year-old man was diagnosed with invasive ductal carcinoma (T4d N3 M1, stage IV). He had advanced breast cancer consisting of multiple tumors with skin involvement and redness over the entire left chest region. A computed tomography (CT) scan of the chest revealed a metastatic tumor in the left lung. Histologically, both the primary breast cancer and the metastatic lung tumor were identified as invasive ductal carcinoma that was estrogen receptor-negative (ER)(-) and progesterone receptor-negative (PgR)(-), with a HER2 score of 3+ (IHC). The patient received a combination chemotherapy using trastuzumab and paclitaxel. Two months later, a follow-up chest CT scan showed that the left lung tumor had disappeared, suggesting a good response to trastuzumab and paclitaxel. During trastuzumab treatment, no severe adverse events above grade 3 were observed. This is the first reported case of advanced HER2-positive male breast cancer in which a good response to trastuzumab and paclitaxel was demonstrated at both primary breast cancer and metastatic sites.}, } @article {pmid18546481, year = {2007}, author = {Alexe, G and Dalgin, GS and Scanfeld, D and Tamayo, P and Mesirov, JP and Ganesan, S and Delisi, C and Bhanot, G}, title = {Breast cancer stratification from analysis of micro-array data of micro-dissected specimens.}, journal = {Genome informatics. International Conference on Genome Informatics}, volume = {18}, number = {}, pages = {130-140}, pmid = {18546481}, issn = {0919-9454}, mesh = {Breast Neoplasms/*classification/genetics/pathology ; Case-Control Studies ; Disease Progression ; Gene Expression Profiling ; Genes, erbB-2 ; Humans ; *Oligonucleotide Array Sequence Analysis ; Receptors, Estrogen/genetics ; }, abstract = {We describe a new method based on principal component analysis and robust consensus ensemble clustering to identify and elucidate the subtypes of breast cancer disease. The method was applied to microarray gene expression data using micro-dissection of samples from 36 breast cancer patients with at least two of three pathological stages of disease. Controls were normal breast epithelial cells from 3 disease free patients. Our method identified an optimum set of genes and strong, stable clusters which correlated well with clinical classification into Luminal, Basal and Her2+ subtypes based on ER, PR and Her2 status. It also revealed a hierarchical portrait of disease progression through various grades and stages and identified genes and functional pathways for each stage, grade and disease subtype. We found that gene expression heterogeneity across subtypes is much greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes are distinct disease processes. The averaging over data perturbations and clustering methods is critical in the robust identification of subtypes and gene markers for grade and progression.}, } @article {pmid18538170, year = {2008}, author = {Kojima, Y and Akimoto, K and Nagashima, Y and Ishiguro, H and Shirai, S and Chishima, T and Ichikawa, Y and Ishikawa, T and Sasaki, T and Kubota, Y and Inayama, Y and Aoki, I and Ohno, S and Shimada, H}, title = {The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors.}, journal = {Human pathology}, volume = {39}, number = {6}, pages = {824-831}, doi = {10.1016/j.humpath.2007.11.001}, pmid = {18538170}, issn = {1532-8392}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/*pathology/therapy ; Carcinoma, Ductal, Breast/enzymology/secondary/therapy ; Carcinoma, Intraductal, Noninfiltrating/enzymology/secondary/therapy ; Cell Polarity ; Combined Modality Therapy ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Isoenzymes/*metabolism ; Middle Aged ; Neoplasm Staging ; Protein Kinase C/*metabolism ; Signal Transduction ; }, abstract = {Breast cancer is one of the common malignant diseases among women in Japan as well as in western countries, and its incidence continues to increase. Normal mammary duct epithelial cells exhibit a well-organized apicobasal polarity, which forms the basis for their specific structure and function. Although the loss of epithelial cell polarity is one of the major changes that occur during the progression of tumor cells, including breast cancer, the underlying molecular mechanisms for this, as well as their relationship to other changes such as increased proliferation and metastasis, remain to be elucidated. The atypical protein kinase C lambda/iota (aPKC lambda/iota) is involved in several signal transduction pathways, including the establishment of epithelial cell polarity. In this study we evaluated the expression and localization of aPKC lambda/iota in breast cancer by immunohistochemistry and compared our findings with the clinicopathologic factors associated with the tumor specimens. We detected aPK Clambda/iota protein overexpression in 88 of the 110 breast cancer cases (80.0%) under study, expect for decreased expression in a few cases. The immunoreactivity of aPK Clambda/iota was generally weak in ductal carcinoma in situ, but strong in invasive ductal carcinoma (IDC; P = .022). The correlation between apical or cytoplasmic aPKC lambda/iota localization and tumor pathologic type (ie, atypical ductal hyperplasia, ductal carcinoma in situ. or IDC) was also demonstrated (P < .001). These results thus indicate that the normal apicobasal polarity is lost upon the progression of a breast lesion to IDC. This is also the first evidence to show aPKC lambda/iota overexpression in breast cancer and demonstrates that its localization is associated with the trend of pathologic type of the tumor.}, } @article {pmid18537548, year = {2008}, author = {Arai, K and Takano, S and Teratani, T and Ito, Y and Yamada, T and Nozawa, R}, title = {S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast.}, journal = {Current cancer drug targets}, volume = {8}, number = {4}, pages = {243-252}, doi = {10.2174/156800908784533445}, pmid = {18537548}, issn = {1873-5576}, mesh = {Base Sequence ; Blotting, Western ; Breast Neoplasms/*metabolism/pathology ; Calgranulin A/*metabolism ; Calgranulin B/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Line, Tumor ; DNA Primers ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {S100 protein A8 and A9 naturally form a stable heterocomplex. Recently, we have proved that S100A9 overexpression in various adenocarcinomas is associated with poor tumor differentiation. In this study, we examined the relationship between the expression of each protein and the pathological parameters that reflect the aggressiveness of carcinoma, in invasive ductal carcinoma (IDC) of the breast. Serial paraffin-embedded tissue sections from 101 IDC cases were immunostained with respective monoclonal antibodies, and the results were as follows: 1) A positive correlation of immunoreactivity between S100A8 and S100A9 was noticed (r=0.873 and P<0.0001); 2) The percentage of S100A9-positive tumor cells was higher than that of S100A8-positive tumor cells (P<0.001), and S100A8 alone was not detected in any case; 3) Overlap between S100A8 and S100A9 staining patterns was found in the corresponding tissue areas, but S100A9 positivity was also observed in S100A8-negative tumor cells; 4) The immunopositivity for each protein also correlated with the mitotic activity, MIB-1 index, HER2 overexpression, node metastasis, and poor pT categories and pStage (P<0.05); 5) Co-expression of both proteins was associated with poor tumor differentiation, vessel invasion, node metastasis, and poor pStage (P<0.05). Furthermore, co-expression of the proteins was also observed in MCF-7 cells, and it was suggested that the immunolocalization is related with cell cycle. Our conclusions are as follows: 1) It is suggested that S100A8 is S100A9-dependently expressed and acquires the protein stability by S100A8/A9 heterocomplex formation; 2) S100A8 and S100A9 overexpression should be considered marker of poor prognosis in IDC.}, } @article {pmid18535764, year = {2008}, author = {Kimura, W}, title = {Strategies for the treatment of invasive ductal carcinoma of the pancreas and how to achieve zero mortality for pancreaticoduodenectomy.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {15}, number = {3}, pages = {270-277}, doi = {10.1007/s00534-007-1305-7}, pmid = {18535764}, issn = {0944-1166}, mesh = {Carcinoma, Pancreatic Ductal/*surgery ; Choledochostomy ; Drainage/methods ; Frozen Sections ; Gastric Bypass ; Humans ; Mesenteric Artery, Superior/surgery ; Mesenteric Veins/surgery ; Pancreas/innervation ; Pancreatic Neoplasms/*surgery ; Pancreaticoduodenectomy/*methods/mortality ; }, abstract = {Although various therapeutic modalities are available for carcinoma of the pancreas, "curative resection" is the most important. Thus, the aim of surgery for carcinoma of the pancreas is local complete resection of the carcinoma. Carcinoma of the head of the pancreas invades through the pancreatic parenchyma, following the arteries, veins, and especially nerves between the parenchyma and fusion fascia, and then spreads horizontally toward the superior mesenteric artery or celiac axis. We suggest techniques for resection of the extrapancreatic nerve plexus in the head of the pancreas during a Whipple procedure for carcinoma of the pancreas, from the perspective of surgical anatomy and pathology, to achieve "curative resection". We suggest that: (1) en-bloc resection of the right side of the superior nerve plexus and the first and second nerve of the pancreatic head should be performed. With this technique, it is possible to avoid cutting these nerves. It is easy to perform this procedure, as follows. First, the superior mesenteric artery and vein are encircled with tape. Next, the superior mesenteric artery should be moved to the right side of the superior mesenteric vein under this vein. In addition, (2) the entire cut end of the nerve plexus should be investigated during the operation, using frozen specimens, and confirmed to be negative for cancer. If the cut end is positive for cancer, additional resection of the nerve plexus should be performed to achieve curative resection. It is impossible to completely determine whether the cut end of the nerve plexus is positive or negative for carcinoma after surgery, because the cut end is long and some specimens are deformed by formalin fixation; thus, it is difficult to identify the true surgical cut end. With regard to reconstruction, we perform a modified Child method with pancreaticojejunostomy (end-to-side), choledochoduodenostomy (also end-to-side), and gastrojejunostomy with Braun's anastomosis. The greater omentum is set around the pancreaticojejunostomy to prevent pancreatic juice from spreading in the abdomen. Careful management of the intraabdominal drainage tubes after the operation is crucial. With the operative procedure and postoperative controls described above, operative mortality was zero in 114 consecutive patients in our series who underwent pancreaticoduodenectomy.}, } @article {pmid18524845, year = {2008}, author = {Yan, Z and Zou, H and Tian, F and Grandis, JR and Mixson, AJ and Lu, PY and Li, LY}, title = {Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth.}, journal = {Molecular cancer therapeutics}, volume = {7}, number = {6}, pages = {1355-1364}, pmid = {18524845}, issn = {1535-7163}, support = {P50 CA097190/CA/NCI NIH HHS/United States ; CA097190/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis/drug effects ; *Autophagy/drug effects ; Breast Neoplasms/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Epithelial Cells/drug effects/*pathology ; ErbB Receptors/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing/drug effects ; Head and Neck Neoplasms/genetics/pathology ; Humans ; Membrane Proteins ; Mice ; Mice, Nude ; Nanoparticles ; Neoplasms/genetics/*pathology ; Neoplasms, Squamous Cell/genetics/pathology ; Polymers ; RNA, Small Interfering/pharmacology ; Signal Transduction/drug effects ; *Xenograft Model Antitumor Assays ; }, abstract = {The rhomboid family of genes carry out a wide range of important functions in a variety of organisms. Little is known, however, about the function of the human rhomboid family-1 gene (RHBDF1). We show here that RHBDF1 function is essential to epithelial cancer cell growth. RHBDF1 mRNA level is significantly elevated in clinical specimens of invasive ductal carcinoma of the breast, and the protein is readily detectable in human breast cancer or head and neck cancer cell lines. Silencing the RHBDF1 gene with short interfering RNA (siRNA) results in apoptosis in breast cancer MDA-MB-435 cells and autophagy in head and neck squamous cell cancer 1483 cells. The treatment also leads to significant down-modulation of activated AKT and extracellular signal-regulated kinase in the cells, suggesting that critically diminished strength of these growth signals may be the key attributes of the induction of cell death. Furthermore, silencing the RHBDF1 gene in MDA-MB-435 or 1483 xenograft tumors on athymic nude mice by using i.v. administered histidine-lysine polymer nanoparticle-encapsulated siRNA results in marked inhibition of tumor growth. Our findings indicate that RHBDF1 has a pivotal role in sustaining growth signals in epithelial cancer cells and thus may serve as a therapeutic target for treating epithelial cancers.}, } @article {pmid18509722, year = {2008}, author = {Yoshikawa, MI and Ohsumi, S and Sugata, S and Kataoka, M and Takashima, S and Mochizuki, T and Ikura, H and Imai, Y}, title = {Relation between cancer cellularity and apparent diffusion coefficient values using diffusion-weighted magnetic resonance imaging in breast cancer.}, journal = {Radiation medicine}, volume = {26}, number = {4}, pages = {222-226}, pmid = {18509722}, issn = {0288-2043}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {PURPOSE: The purpose of this study was to examine the relation between cancer cellularity and the apparent diffusion coefficient (ADC) value using diffusion-weighted magnetic resonance imaging in breast cancer.

MATERIALS AND METHODS: The subjects were 27 women who had undergone operation for breast cancer. There were 27 breast cancer lesions, 24 of which were invasive ductal carcinoma (IDC) and 3 of which were noninvasive ductal carcinoma (NIDC).

RESULTS: The mean ADC values of IDC, NIDC, and normal breasts were 1.07 +/- 0.19 .10(-3), 1.42 +/- 0.17 .10(-3), and 1.96 +/- 0.21 .10(-3) mm(2)/s, respectively. The mean ADC values of IDC and NIDC were significantly different from that of normal breasts (P < 0.001 each). The mean ADC values were also significantly different between IDC and NIDC (P < 0.001). There was no correlation between the ADC value and cancer cellularity.

CONCLUSION: The mean ADC values for breast cancer were significantly different from that of normal breasts. The mean ADC value for breast cancer did not significantly correlate with cancer cellularity but did correlate with histological types.}, } @article {pmid18507821, year = {2008}, author = {Gonzalez, LO and Corte, MD and Vazquez, J and Junquera, S and Sanchez, R and Alvarez, AC and Rodriguez, JC and Lamelas, ML and Vizoso, FJ}, title = {Androgen receptor expresion in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors.}, journal = {BMC cancer}, volume = {8}, number = {}, pages = {149}, pmid = {18507821}, issn = {1471-2407}, mesh = {Breast Neoplasms/*metabolism/pathology/physiopathology ; Carcinoma, Ductal, Breast/*metabolism/pathology/physiopathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Metalloproteases/*biosynthesis ; Prognosis ; Protein Array Analysis ; Receptors, Androgen/*biosynthesis ; Survival Analysis ; Tissue Inhibitor of Metalloproteinases/biosynthesis ; }, abstract = {BACKGROUND: In the present study we analyze, in patients with breast cancer, the tumor expression of androgen receptors (AR), its relationship with clinicopathological characteristics and with the expression of several matrix metalloproteases (MMPs) and their inhibitors (TIMPs), as well as with prognosis.

METHODS: An immunohistochemical study was performed using tissue microarrays and specific antibodies against AR, MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 2,800 determinations on tumor specimens from 111 patients with primary invasive ductal carcinoma of the breast (52 with axillary lymph node metastases and 59 without them) and controls were performed. Staining results were categorized using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically.

RESULTS: A total of 83 cases (74.8%) showed a positive immunostaining for AR, but with a wide variation in the staining score values. There were no significant associations between the total immunostaining scores for AR and any clinicopathological parameters. However, score values for MMP-1, -7 and -13, were significantly higher in AR-positive tumors than in AR-negative tumors. Likewise, when we considered the cellular type expressing each factor, we found that AR-positive tumors had a higher percentage of cases positive for MMP-1, -7, -11, and TIMP-2 in their malignant cells, as well as for MMP-1 in intratumoral fibroblasts. On the other hand, multivariate analysis demonstrated that patients with AR-positive tumors have a significant longer overall survival than those with AR-negative breast carcinomas (p = 0.03).

CONCLUSION: Our results confirm that AR are commonly expressed in breast cancer, and are correlated with the expression of some MMPs and TIMP-2. Although we found a specific value of AR expression to be a prognostic indicator in breast cancer, the functional role of AR in these neoplasms is still unclear and further data are needed in order to clarify their biological signification in breast cancer.}, } @article {pmid18505551, year = {2008}, author = {Scholz, M and Fraunholz, MJ}, title = {A computational model of gene expression reveals early transcriptional events at the subtelomeric regions of the malaria parasite, Plasmodium falciparum.}, journal = {Genome biology}, volume = {9}, number = {5}, pages = {R88}, pmid = {18505551}, issn = {1474-760X}, mesh = {Animals ; DNA, Protozoan/*genetics ; Models, Genetic ; Plasmodium falciparum/*genetics ; Principal Component Analysis ; Telomere/*genetics ; *Transcription, Genetic ; }, abstract = {BACKGROUND: The malaria parasite, Plasmodium falciparum, replicates asexually in a well-defined infection cycle within human erythrocytes (red blood cells). The intra-erythrocytic developmental cycle (IDC) proceeds with a 48 hour periodicity.

RESULTS: Based on available malaria microarray data, which monitored gene expression over one complete IDC in one-hour time intervals, we built a mathematical model of the IDC using a circular variant of non-linear principal component analysis. This model enables us to identify rates of expression change within the data and reveals early transcriptional events at the subtelomeres of the parasite's nuclear chromosomes.

CONCLUSION: A delay between subtelomeric and central gene activities suggests that key events of the IDC are initiated at the subtelomeric regions of the P. falciparum nuclear chromosomes.}, } @article {pmid18498127, year = {2008}, author = {Mhuircheartaigh, JN and Curran, C and Hennessy, E and Kerin, MJ}, title = {Prospective matched-pair comparison of outcome after treatment for lobular and ductal breast carcinoma.}, journal = {The British journal of surgery}, volume = {95}, number = {7}, pages = {827-833}, doi = {10.1002/bjs.6042}, pmid = {18498127}, issn = {1365-2168}, mesh = {Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/mortality/*surgery ; Carcinoma, Lobular/*surgery ; Female ; Humans ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Whether the prognosis of invasive lobular carcinoma is different from that of other invasive breast cancers is controversial. The aim of this study was to compare the outcome in age- and stage-matched patients with lobular carcinoma and those with invasive breast cancer, and in particular to compare predictors of outcome.

METHODS: Data were obtained from a prospectively maintained database that included patients who had breast surgery for invasive cancer. Patients were matched for International Union Against Cancer stage and age at diagnosis within 5 years. Two patients with invasive ductal carcinoma were matched to each patient with invasive lobular carcinoma.

RESULTS: There was no significant difference between invasive ductal and lobular carcinomas in terms of overall survival. Oestrogen receptor (ER)-positive invasive ductal carcinoma had a better prognosis than ER-positive invasive lobular carcinoma (P = 0.011). Similarly, ER-negative invasive ductal carcinoma was associated with worse survival than ER-negative invasive lobular carcinoma (P = 0.054).

CONCLUSION: These results suggested that the differences in outcome between invasive ductal and lobular carcinomas may be determined by ER status.}, } @article {pmid18497952, year = {2008}, author = {Xu, S and Wei, B and Zhang, H and Qing, M and Bu, H}, title = {Evidence of chromosomal alterations in pure usual ductal hyperplasia as a breast carcinoma precursor.}, journal = {Oncology reports}, volume = {19}, number = {6}, pages = {1469-1475}, pmid = {18497952}, issn = {1021-335X}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human/*genetics ; DNA, Neoplasm/genetics ; Female ; Humans ; Hyperplasia/genetics/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Precancerous Conditions/*genetics/pathology ; }, abstract = {Previous studies have shown the chromosomal alterations in usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) in the breast with bilateral ductal hyperplasia or adjacent to invasive ductal carcinoma (IDC). However, the role of UDH as a putative precursor of breast IDC is not clear and has not been fully addressed. The aim of this study was to clarify the role of UDH in breast carcinoma pathogenesis. To investigate chromosomal imbalances and commonality, samples of pure unilateral UDH (n=20) were obtained by laser capture microdissection and analyzed by comparative genomic hybridization. Other ductal lesions, including ADH (n=2), high-grade DCIS (n=3), and grade III IDC (n=5), were assessed at the same time for comparison. The mean values of alteration were 1.95 (39/20) in UDH, 9.5 (19/2) in ADH, 11.0 (33/3) in DCIS and 18.2 (89/5) in IDC, respectively. Some common predisposition regions for the deletions were at chromosomes 1p36-pter, 13q11-14, and 16q11-23, while the high frequency amplification regions were 1q31-qter, 3p21-pter, 6p21-pter, 11q11-14, 12q11-qter, 13q21-qter, 16p12-pter, 17q12-22, and 20q. The genetic abnormalities in the spectrum of breast ductal hyperplasia revealed that the deletion of DNA copy in UDH was the lowest, and gradually increased in the lineages of ADH, DCIS and IDC. Results showed that a significant portion of UDH shares common genetic alterations with ADH, DCIS and IDC, indicating UDH as a precursor of invasive breast ductal carcinoma.}, } @article {pmid18496442, year = {2008}, author = {Teal, CB and Brem, RF and Rapelyea, JA and Akin, EA}, title = {Nonvisualization of a sentinel lymph node on lymphoscintigraphy requiring reinjection of sulfur colloid in a patient with breast cancer.}, journal = {Clinical nuclear medicine}, volume = {33}, number = {6}, pages = {389-390}, doi = {10.1097/RLU.0b013e318170d4b9}, pmid = {18496442}, issn = {1536-0229}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/*pathology ; False Negative Reactions ; Female ; Humans ; Image Enhancement/methods ; Injections, Intralesional ; Lymph Nodes/*diagnostic imaging/*pathology ; Radionuclide Imaging ; Radiopharmaceuticals/administration & dosage ; Sentinel Lymph Node Biopsy/*methods ; Technetium Tc 99m Sulfur Colloid/*administration & dosage ; }, abstract = {PURPOSE: The injection techniques and use of lymphoscintigraphy for sentinel lymph node (SLN) biopsy in breast cancer patients vary. Some do not advocate routine use of lymphoscintigraphy. The purpose of this case report is to illustrate when lymphoscintigraphy should be used.

METHODS: At our institution, we use periareolar intradermal injections of 0.6 mCi Tc-99m sulfur colloid followed by lymphoscintigraphy with reported identification rates greater than 99%. The only patient in our series who did not have a SLN identified had presented after excisional biopsy of an upper outer quadrant cancer. We report the case of another patient who presented after excision of an upper outer quadrant invasive ductal carcinoma and had no evidence of lymphatic drainage on lymphoscintigraphy after the periareolar injections of radioisotope.

RESULTS: Additional injections of 0.4 mCi Tc-99m sulfur colloid were performed lateral to the incision in the upper outer quadrant. On lymphoscintigraphy a SLN was visualized and was subsequently successfully identified intraoperatively.

CONCLUSION: This case report supports the value of lymphoscintigraphy for successful identification of a SLN in a patient with prior surgery. We therefore recommend imaging patients who have had prior breast surgery, particularly excisions in the upper outer quadrant.}, } @article {pmid18490810, year = {2008}, author = {Farquharson, MJ and Al-Ebraheem, A and Falkenberg, G and Leek, R and Harris, AL and Bradley, DA}, title = {The distribution of trace elements Ca, Fe, Cu and Zn and the determination of copper oxidation state in breast tumour tissue using muSRXRF and muXANES.}, journal = {Physics in medicine and biology}, volume = {53}, number = {11}, pages = {3023-3037}, doi = {10.1088/0031-9155/53/11/018}, pmid = {18490810}, issn = {0031-9155}, mesh = {Breast Neoplasms/*chemistry ; Copper/*analysis ; Female ; Humans ; Oxidation-Reduction ; Spectrometry, X-Ray Emission ; Trace Elements/*analysis ; }, abstract = {A micro beam synchrotron x-ray fluorescence (muSRXRF) technique has been used to determine the localization of metals in primary invasive ductal carcinoma of breast. Nine samples were examined, all of which were formalin fixed tissues arranged as micro arrays of 1.0 mm diameter and 10 microm thickness. Cu was the particular interest in this study although 2D maps of the elements Ca, Fe and Zn, which are also of physiological importance, are presented. The distribution of these metals was obtained at approximately 18 microm spatial resolution and compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cell clusters. Correlations were found between these reference images and the elemental distributions indicating an increase in all element concentrations in the tumour regions of all samples, with the exception of Fe, which in some cases showed a reverse of this trend. On average over all samples the percentage difference from the normal tissue elemental concentrations are Ca approximately 67%, Cu approximately 64% and Zn approximately 145%. Micro x-ray absorption near edge spectroscopy (muXANES) was used to estimate the oxidation state of Cu in 19 normal and 17 tumour regions spread over five samples. The shape and the position of both normal and tumour regions suggest that they contain mixtures of copper ions with a significant fraction of Cu2+. However, the shape of the spectra does not exclude the presence of Cu+. Tumour regions were found to have a higher fraction of Cu+ compared to the normal samples.}, } @article {pmid18490762, year = {2008}, author = {Woszczek, G and Chen, LY and Nagineni, S and Shelhamer, JH}, title = {IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {180}, number = {11}, pages = {7597-7603}, pmid = {18490762}, issn = {0022-1767}, support = {Z01 CL008071-04/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Cell Migration Inhibition ; Chemokine CCL5/immunology/metabolism ; Chemotaxis ; Chemotaxis, Leukocyte ; Cysteine/immunology/*metabolism ; Dendritic Cells/*immunology/metabolism ; Humans ; Interleukin-10/immunology/*metabolism ; Leukotriene D4/immunology/metabolism ; Leukotrienes/immunology/*metabolism ; Monocytes/*immunology/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering ; Receptors, Leukotriene/deficiency/genetics/*metabolism ; }, abstract = {The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors' mRNA in a time- and concentration-dependent fashion. cysLT-induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist MK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D(4) (LTD(4)) was also inhibited by IL-10. LTD(4) enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD(4)-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes.}, } @article {pmid18489882, year = {2008}, author = {Nielsen, US and Jakobsen, EH}, title = {[Breast cancer in 32-year-old male].}, journal = {Ugeskrift for laeger}, volume = {170}, number = {19}, pages = {1663}, pmid = {18489882}, issn = {1603-6824}, mesh = {Adult ; *Breast Neoplasms, Male/diagnosis/drug therapy/surgery ; *Carcinoma, Ductal, Breast/diagnosis/drug therapy/surgery ; Humans ; Male ; Nipples/metabolism ; Prognosis ; }, abstract = {UNLABELLED: A young man with daily nipple discharge was told to wait and see. After 18 months, at 32, he developed a subareolar lump which proved to be invasive ductal carcinoma. There were no epidemiological or genetic risk factors, no mutations in BRCA 1 + 2. Male breast cancer (MBC) patients have a lower survival rate than females due to a delay in diagnosis. Greater focus on MBC is necessary in order to change this.

TREATMENT: We chose to follow the guidelines for young women. Some studies imply that early MBC is more benign but there are no randomised trials on treatment.}, } @article {pmid18488218, year = {2009}, author = {Vujanovic, L and Whiteside, TL and Potter, DM and Chu, J and Ferrone, S and Butterfield, LH}, title = {Regulation of antigen presentation machinery in human dendritic cells by recombinant adenovirus.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {58}, number = {1}, pages = {121-133}, pmid = {18488218}, issn = {1432-0851}, support = {P01 CA109688/CA/NCI NIH HHS/United States ; R01 CA110249/CA/NCI NIH HHS/United States ; R01 CA110249-03/CA/NCI NIH HHS/United States ; R01 CA138188/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/*genetics/physiology ; *Antigen Presentation/genetics/immunology/physiology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Dendritic Cells/*immunology/metabolism ; Flow Cytometry ; *Genetic Vectors ; Humans ; Lymphocyte Activation ; Recombinant Proteins/genetics ; Transduction, Genetic ; }, abstract = {Recombinant adenoviral vectors (AdV) are potent vehicles for antigen engineering of dendritic cells (DC). DC engineered with AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells. To determine the impact of AdV on the HLA class I antigen presentation pathway, we investigated the effects of AdV transduction on antigen processing machinery (APM) components in human DC. Interactions among AdV transduction, maturation, APM regulation and T cell activation were investigated. The phenotype and cytokine profile of DC transduced with AdV was intermediate, between immature (iDC) and matured DC (mDC). Statistically significant increases in expression were observed for peptide transporters TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV transduction. AdV transduction enhanced the expression of APM components and surface markers on mDC, and these changes were further modulated by the timing of DC maturation. Engineering of matured DC to express a tumor-associated antigen stimulated a broader repertoire of CD8+ T cells, capable of recognizing immunodominant and subdominant epitopes. These data identify molecular changes in AdV-transduced DC (AdV/DC) that could influence T cell priming and should be considered in design of cancer vaccines.}, } @article {pmid18484683, year = {2008}, author = {Marchiò, C and Iravani, M and Natrajan, R and Lambros, MB and Savage, K and Tamber, N and Fenwick, K and Mackay, A and Senetta, R and Di Palma, S and Schmitt, FC and Bussolati, G and Ellis, LO and Ashworth, A and Sapino, A and Reis-Filho, JS}, title = {Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {215}, number = {4}, pages = {398-410}, doi = {10.1002/path.2368}, pmid = {18484683}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/immunology ; Carcinoma, Ductal, Breast/*genetics/immunology ; Cyclin D1/genetics ; Disease Progression ; Female ; Gene Amplification ; Gene Expression Profiling/*methods ; Genetic Markers ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; *Oligonucleotide Array Sequence Analysis ; Oncogenes ; }, abstract = {Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.}, } @article {pmid18476884, year = {2008}, author = {Nggada, HA and Yawe, KD and Abdulazeez, J and Khalil, MA}, title = {Breast cancer burden in Maiduguri, North eastern Nigeria.}, journal = {The breast journal}, volume = {14}, number = {3}, pages = {284-286}, doi = {10.1111/j.1524-4741.2008.00576.x}, pmid = {18476884}, issn = {1524-4741}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/epidemiology ; *Cost of Illness ; Female ; Humans ; Male ; Middle Aged ; Nigeria/epidemiology ; Retrospective Studies ; }, abstract = {Breast cancer is a global disease and incidence continues to rise especially in the sub-Saharan Africa. In Nigeria, breast cancer is currently the most common malignancy. This study aimed at describing the pattern of breast cancers in Maiduguri and to determine if there is any significant changing trend of frequency. This is a retrospective review data of breast cancers between 2001 and 2005 in the University of Maiduguri Teaching Hospital Cancer Registry. A total of 1,216 cases of cancers were registered within the study period and breast cancer accounted for 13.9%. There were 490 breast biopsy specimens and breast cancer accounted for 34.5%. There were 161 females and 8 males breast cancer within the study period giving a F:M ratio 20:1. There were four cases of bilateral breast cancers. The age ranges between 17 and 85 years and the peak age group was 40-49 years which accounted for 61 cases (36.1%). The commonest histologic type of breast cancer was invasive ductal carcinoma which accounted for 82.6%; invasive lobular (6.6%); medullary (4.3%); colloid (1.7%); papillary (1.1%); and others (5.1%). In conclusion, breast cancer is on the increase in our environment and therefore there is need for public enlightenment, screening all women at risk, early detection of the lesion, and proper management in our health institution.}, } @article {pmid18473330, year = {2008}, author = {Simpson, PT and Reis-Filho, JS and Lambros, MB and Jones, C and Steele, D and Mackay, A and Iravani, M and Fenwick, K and Dexter, T and Jones, A and Reid, L and Da Silva, L and Shin, SJ and Hardisson, D and Ashworth, A and Schmitt, FC and Palacios, J and Lakhani, SR}, title = {Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas.}, journal = {The Journal of pathology}, volume = {215}, number = {3}, pages = {231-244}, doi = {10.1002/path.2358}, pmid = {18473330}, issn = {0022-3417}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*genetics ; Carcinoma, Ductal, Breast/chemistry/genetics ; Carcinoma, Lobular/chemistry/*genetics ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Loss of Heterozygosity ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Pleomorphic lobular carcinomas (PLC) of the breast display histological features associated with classic invasive lobular carcinoma (ILC), yet they also exhibit more conspicuous nuclear atypia and pleomorphism, and an aggressive clinical behaviour. From a breast cancer progression perspective, it is unclear whether PLC is a variant of ILC or is a high-grade invasive ductal carcinoma (IDC) that has lost E-cadherin. The molecular features of 26 PLC were studied using immunohistochemistry [oestrogen receptor (ER), progesterone receptor (PR), HER2, p53 and E-cadherin], 0.9 Mb resolution, microarray-based comparative genomic hybridization (aCGH), fluorescent (FISH) and chromogenic (CISH) in situ hybridization and loss of heterozygosity. Comparative analysis was performed with aCGH data from PLC with classic ILC (16 cases) and high grade IDC (35 cases). PLCs were frequently ER- and PR-positive, E-cadherin-negative and occasionally HER2- and p53-positive. Recurrent copy number changes identified by aCGH included gains on 1q, 8q, 11q, 12q, 16p and 17q and losses on 8p, 11q, 13q, 16q and Xq. Highly recurrent 1q+ (100% of cases), 16p+ (93%), 11q- (53%) and 16q- (93%) and evidence of the der(1;16)/der(16)t(1;16) rearrangement, as detected by FISH, suggested that PLC had a 'lobular genotype'. Focal amplifications were evident at 8p12-p11, 8q24, 11q13.1-q14.1, 12q14, 17q12 and 20q13. Loss of BRCA2 was detected in 40% of PLC by LOH. Comparative analysis of aCGH data suggested the molecular features of PLC (ER/PR-positive, E-cadherin-negative, 1q+, 11q(-), 16p+ and 16q(-)) were more closely related to those of ILC than IDC, implicating an overlapping developmental pathway for these lobular tumour types. Molecular alterations found in PLC that are more typical of high-grade IDC than ILC (p53 and HER2 positivity, 8q+, 17q24-q25+, 13q(-) and amplification of 8q24, 12q14, 17q12 and 20q13) are likely to drive the high-grade and more aggressive biology of PLC.}, } @article {pmid18473143, year = {2008}, author = {Skandarajah, AR and Field, L and Yuen Larn Mou, A and Buchanan, M and Evans, J and Hart, S and Mann, GB}, title = {Benign papilloma on core biopsy requires surgical excision.}, journal = {Annals of surgical oncology}, volume = {15}, number = {8}, pages = {2272-2277}, doi = {10.1245/s10434-008-9962-6}, pmid = {18473143}, issn = {1534-4681}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast/*pathology/surgery ; Breast Neoplasms/*pathology/surgery ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Papilloma/*pathology/*surgery ; Retrospective Studies ; }, abstract = {BACKGROUND: When a papillary lesion is identified on core biopsy of an impalpable breast lesion, standard practice involves excisional biopsy. Recent literature has questioned the need for surgical excision in patients with benign core biopsy and radiological concordance. Our aim was to assess whether surgical excision is required by targeting this concordant group in a large screen-detected population.

METHODS: A retrospective review of a prospectively collected database of all benign papillary core biopsies between February 1995 and September 2007 at North Western Breast Screen and Monash Breast Screen in Melbourne, Australia was performed. All patients had surgical excision, enabling correlation between core and final excisional biopsy results on all lesions. All histology reports were reviewed and the radiology was reassessed.

RESULTS: During a 14-year period, 5783 core biopsies were performed from 633,163 screening mammograms. Eighty patients (0.01%) had benign papilloma on core biopsy, no patients had atypia on core biopsy, and all patients had benign radiological features. Of the 80 patients, 15 patients were found to have ductal carcinoma in situ (8) or invasive ductal carcinoma (7) on final pathology, yielding a 19% malignant rate.

CONCLUSION: Core biopsy showing benign papillary lesion, even where radiology is also suggestive of a benign process, cannot exclude malignancy, and therefore surgical excision is required.}, } @article {pmid18469353, year = {2008}, author = {Laser, J and Cangiarella, J and Singh, B and Melamed, J and Chiriboga, L and Yee, H and Darvishian, F}, title = {Invasive lobular carcinoma of the breast: role of endothelial lymphatic marker D2-40.}, journal = {Annals of clinical and laboratory science}, volume = {38}, number = {2}, pages = {99-104}, pmid = {18469353}, issn = {1550-8080}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/*metabolism/pathology ; Carcinoma, Lobular/*diagnosis/*metabolism/pathology ; Cohort Studies ; Female ; Humans ; Lymphatic Metastasis/pathology ; Lymphatic Vessels/pathology ; Middle Aged ; Prognosis ; }, abstract = {Lymphovascular invasion (LVI) of breast cancer is an independent adverse prognosticator that is associated with increased regional and distant tumor recurrence. LVI is infrequently encountered in invasive lobular carcinoma when compared to invasive ductal carcinoma. We employed D2-40 antibody, a novel marker for lymphatic endothelial cells, in an attempt to enhance the detection of LVI in invasive lobular carcinomas. We identified 78 patients with invasive lobular carcinoma with known axillary status, who were studied between 2003 and 2006. D2-40 antibody was applied to one representative paraffin block from each case and the results were compared to LVI on routine histology. LVI was identified in 12 (15%) and 19 (24%) cases by routine histology and D2-40 antibody, respectively. Eleven of 12 patients (92%) with LVI identified by routine histology had axillary nodal metastasis compared to 14 of 19 patients (74%) with LVI identified by D2-40 antibody. LVI was missed by routine histology in 8 cases (10%). D2-40 antibody enhanced the identification of LVI by 9% in node negative patients. D2-40 antibody increased the identification of LVI by 12% in classic invasive lobular carcinoma. In conclusion, D2-40 antibody staining may be useful as an adjunct in detecting LVI in invasive lobular carcinoma, especially in node-negative patients with the classic variant of invasive lobular carcinoma.}, } @article {pmid18464918, year = {2008}, author = {Olcina, M and Merck, B and Giménez-Climent, MJ and Almenar, S and Sancho-Merle, MF and Llopis, F and Vázquez-Albadalejo, C}, title = {Radiation-Induced Leiomyosarcoma after Breast Cancer Treatment and TRAM Flap Reconstruction.}, journal = {Sarcoma}, volume = {2008}, number = {}, pages = {456950}, pmid = {18464918}, issn = {1357-714X}, abstract = {The development of a radiation-induced sarcoma (RIS) in the post mastectomy thoracic treatment volume is an infrequent, but recognized, event. Its frequency is rising in relation with increasing survival of breast cancer patients treated with adjuvant radiation therapy, and is associated with poor prognosis despite treatment. We present a case of leiomyosarcoma in a patient who underwent mastectomy followed by radiotherapy for invasive ductal carcinoma. A delayed TRAM flap reconstruction was performed 10 years after and a rapid growing mass under the reconstructed flap appeared, on routine follow-up, twenty years later. This report analyzes the diagnostic and therapeutic approach of patients with RIS.}, } @article {pmid18460845, year = {2008}, author = {Hatakenaka, M and Soeda, H and Yabuuchi, H and Matsuo, Y and Kamitani, T and Oda, Y and Tsuneyoshi, M and Honda, H}, title = {Apparent diffusion coefficients of breast tumors: clinical application.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {7}, number = {1}, pages = {23-29}, doi = {10.2463/mrms.7.23}, pmid = {18460845}, issn = {1347-3182}, mesh = {Adenocarcinoma, Mucinous/*diagnosis/pathology/surgery ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast/*pathology/surgery ; Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/pathology/surgery ; Diagnosis, Differential ; Diffusion ; Diffusion Magnetic Resonance Imaging/*methods ; Echo-Planar Imaging/*methods ; Female ; Fibroadenoma/*diagnosis/pathology/surgery ; Humans ; Image Processing, Computer-Assisted/methods ; Middle Aged ; }, abstract = {PURPOSE: To evaluate the usefulness of apparent diffusion coefficient (ADC) for the differential diagnosis of breast tumors and to determine the relation between ADC and tumor cellularity.

MATERIALS AND METHODS: One hundred and thirty-six female patients (age range, 17-83 years; average age, 51.7 years) with 140 histologically proven breast tumors underwent diffusion-weighted magnetic resonance (MR) imaging (DWI) using the spin-echo echo-planar technique, and the ADCs of the tumors were calculated using 3 different b values, 0, 500, and 1000 s/mm(2). The diagnoses consisted of fibroadenoma (FA, n=16), invasive ductal carcinoma, not otherwise specified (IDC, n=117), medullary carcinoma (ME, n=3) and mucinous carcinoma (MU, n=4). Tumor cellularity was calculated from surgical specimens. The ADCs of breast tumors and cellularity were compared between different histological types by analysis of variance and Scheffe's post hoc test. The correlation between tumor cellularity and ADC was analyzed by Pearson correlation test.

RESULTS: Significant differences were observed in ADCs between FA and all types of cancers (P<0.05) and between MU and other types of cancers (P<0.01) and in cellularity between FA and cancers except MU (P<0.01) and between MU and other types of cancers (P<0.01). There was an inverse correlation between ADC and tumor cellularity (P<0.01, r(2)=0.451).

CONCLUSIONS: The ADC may potentially help in differentiating benign and malignant breast tumors. Tumor ADC correlates inversely with tumor cellularity.}, } @article {pmid18460206, year = {2008}, author = {Segerer, SE and Müller, N and Brandt, Jv and Kapp, M and Dietl, J and Reichardt, HM and Rieger, L and Kämmerer, U}, title = {The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation.}, journal = {Reproductive biology and endocrinology : RB&E}, volume = {6}, number = {}, pages = {17}, pmid = {18460206}, issn = {1477-7827}, mesh = {Actins/analysis ; Activins/pharmacology/*physiology ; Adult ; Antigens, CD/biosynthesis/genetics ; B7-2 Antigen/biosynthesis/genetics ; CD40 Antigens/biosynthesis/genetics ; Cell Differentiation/drug effects ; Cells, Cultured/drug effects/metabolism ; Cytoskeleton/drug effects/ultrastructure ; Dendritic Cells/cytology/*drug effects/metabolism ; Dexamethasone/pharmacology ; Female ; HLA-DR Antigens/biosynthesis ; Humans ; Immune Tolerance/physiology ; Immunoglobulins/biosynthesis/genetics ; Inhibins/pharmacology/*physiology ; Interleukin-1beta/pharmacology ; Interleukin-6/pharmacology ; Male ; Membrane Glycoproteins/biosynthesis/genetics ; Monocytes/cytology/drug effects ; Recombinant Proteins/pharmacology ; T-Lymphocyte Subsets/immunology ; Transforming Growth Factor beta1/pharmacology ; }, abstract = {BACKGROUND: Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.

METHODS: To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.

RESULTS: Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.

CONCLUSION: These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.}, } @article {pmid18458044, year = {2008}, author = {Pestalozzi, BC and Zahrieh, D and Mallon, E and Gusterson, BA and Price, KN and Gelber, RD and Holmberg, SB and Lindtner, J and Snyder, R and Thürlimann, B and Murray, E and Viale, G and Castiglione-Gertsch, M and Coates, AS and Goldhirsch, A and , }, title = {Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {26}, number = {18}, pages = {3006-3014}, doi = {10.1200/JCO.2007.14.9336}, pmid = {18458044}, issn = {1527-7755}, support = {U24 CA075362/CA/NCI NIH HHS/United States ; CA-75362/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/diagnosis/epidemiology/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/pathology/therapy ; Carcinoma, Lobular/diagnosis/epidemiology/*pathology/therapy ; Clinical Trials as Topic ; Disease-Free Survival ; Female ; Humans ; Neoplasm Recurrence, Local/diagnosis/pathology ; }, abstract = {PURPOSE: To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC) with regard to patient and tumor factors, local treatment, and patterns of recurrence.

PATIENTS AND METHODS: Twelve thousand two hundred six breast cancer patients entered onto 15 International Breast Cancer Study Group trials between 1978 and 2002 were categorized as having ILC, IDC, or other/mixed types.

RESULTS: Seven hundred sixty-seven tumors (6.2%) were classified as ILC, 8,607 (70.5%) were classified as IDC, and 2,832 (23.2%) were classified as other. The analysis is limited to the 9,374 patients categorized as either pure IDC or ILC. The median follow-up time was 13 years. Compared with IDC, ILC was associated with older age; larger, better differentiated, and estrogen receptor (ER)-positive tumors; and less vessel invasion. Mastectomy was used more frequently for ILC (P < .01). There was a significant (P < .01) early advantage in disease-free survival and overall survival for the ILC cohort followed by a significant (P < .01) late advantage for the IDC cohort after 6 and 10 years, respectively. Similar patterns were observed in cohorts defined by ER status. ILC was associated with an increased incidence of bone events but a decrease in regional and lung events (all P < .01).

CONCLUSION: ILC is more than a histologic variant of breast cancer. The diagnosis of ILC carries distinct prognostic and biologic implications.}, } @article {pmid18454879, year = {2008}, author = {Ismail, NI and Kaur, G and Hashim, H and Hassan, MS}, title = {Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression.}, journal = {Cancer cell international}, volume = {8}, number = {}, pages = {6}, pmid = {18454879}, issn = {1475-2867}, abstract = {BACKGROUND: Breast cancer is the most common cause of cancer death in the western world. The expression differences of many proteins are associated with breast cancer progression or suppression. The purpose of the study was to determine the expression of nm23 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of nm23 gene product.

METHOD: nm23 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissues from 216 patients.

RESULTS: a similar percentage of cases showed positive cytoplasmic/nuclear staining for nm23 in normal breast tissue (85.7%), primary breast carcinoma node negative (97.5%) and carcinoma with lymph node metastasis (92.1%). Nuclear localization of staining for nm23 protein was higher in infiltrating ductal carcinoma (IDC) node positive (24.3%) and in matched lymph mode metastasis (18.9%) compared to IDC node negative (4.9%). Strong intensity of cytoplasmic/nucleus staining was observed in IDC node negative (42.6%), in IDC node positive (57.1%), and Infiltrating lobular carcinoma (ILC) node negative (44%) compared to normal breast tissue (16.7%).

CONCLUSION: nm23 protein expression appears widely expressed in normal breast, early and advanced breast cancer stages. Interestingly our study found that strong staining intensity and nuclear localization of nm23 protein may prove to be a useful marker of breast cancer progression.}, } @article {pmid18452239, year = {2008}, author = {Shin, O and Kim, SJ and Lee, WI and Kim, JY and Lee, H}, title = {Effective transduction by self-complementary adeno-associated viruses of human dendritic cells with no alteration of their natural characteristics.}, journal = {The journal of gene medicine}, volume = {10}, number = {7}, pages = {762-769}, doi = {10.1002/jgm.1204}, pmid = {18452239}, issn = {1521-2254}, mesh = {DNA Primers/genetics ; Dendritic Cells/*cytology ; Dependovirus ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; *Gene Transfer Techniques ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-4 ; Propidium ; Transduction, Genetic/*methods ; }, abstract = {BACKGROUND: Effective gene delivery techniques are required to genetically manipulate dendritic cells (DCs). We therefore investigated the feasibility of using various self-complementary recombinant adeno-associated virus (scAAV) serotypes to deliver genes to human DCs.

METHODS: Monocytes isolated from healthy volunteers were differentiated to immature DCs (iDC) by incubation with interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor. The iDCs were transduced with scAAV1, 2, 3, 4, 5, 6 or 8 at various multiplicities of infection (MOIs). Transduction efficiency (TE), cell viability and functional characteristics of the transduced DCs were evaluated.

RESULTS: TE of scAAV was three-fold greater than TE of conventional recombinant adeno-associated virus with a single-stranded genome. The TEs of scAAV2, 5, and 6 were much higher than those of the other scAAVs; at 1000 MOI, the TEs were 22.2% +/- 9.5%, 27.0% +/- 8.8% and 28.4% +/- 6.0%, respectively. Exposure of iDCs to 5000 MOI of these viruses increased their TEs, leading to the transduction of nearly the entire DC population. In addition, gene transfer by scAAV did not cause any cytotoxicity. Flow cytometric analysis of scAAV-transduced DCs showed no changes in surface marker profiles. Moreover, transduced cells maintained their functional properties, as represented by active antigen uptake. These cells could efficiently differentiate into mature DCs, as shown by their release of IL-12, the substantial loss of antigen-uptake activity, and the ability of T-cell stimulation.

CONCLUSIONS: These findings strongly indicate that scAAVs, especially subtypes 2, 5 and 6, hold a promising potential as gene delivery tools in human DCs.}, } @article {pmid18449551, year = {2009}, author = {Dian, D and Herold, H and Mylonas, I and Scholz, C and Janni, W and Sommer, H and Friese, K}, title = {Survival analysis between patients with invasive ductal and invasive lobular breast cancer.}, journal = {Archives of gynecology and obstetrics}, volume = {279}, number = {1}, pages = {23-28}, doi = {10.1007/s00404-008-0662-z}, pmid = {18449551}, issn = {1432-0711}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Carcinoma, Lobular/*mortality/pathology ; Disease-Free Survival ; Female ; Histocytochemistry ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: Differences in overall survival (OS) and disease-free survival (DFS) between patients with invasive ductal (IDC) and invasive lobular breast cancer (ILC) are controversial.

STUDY DESIGN: The study population was selected from a database of 5,689 female patients with invasive breast cancer. In order to focus on the impact of tumour histology, all primary metastatic patients and patients with adjuvant chemotherapy or anti-hormonal treatment were excluded. Only patients with pure invasive lobular and invasive ductal histology were included.

RESULTS: Multivariate survival analyses of 2,058 eligible patients confirmed tumour histology as an independent prognostic factor for OS in invasive breast cancer (p = 0.046) but not for DFS (p = 0.599). Kaplan-Meier survival analysis of OS between IDC and ILC patients showed a statistically significantly better OS for patients with ILC (p = 0.0302). DFS was not statistically different (p = 0.6659) between IDC and ILC. Univariate survival analyses of tumour size, tumour grading and nodal status in our study population were highly statistically significant for OS and DFS (p < 0.0000).

CONCLUSION: Patients in our study population with ILC have significantly better OS than patients with IDC. Differences in DFS are not statistically significant.}, } @article {pmid18446625, year = {2008}, author = {Somani, A and Hwang, JS and Chaiwun, B and Tse, GM and Lui, PC and Tan, PH}, title = {Fine needle aspiration cytology in young women with breast cancer: diagnostic difficulties.}, journal = {Pathology}, volume = {40}, number = {4}, pages = {359-364}, doi = {10.1080/00313020802035881}, pmid = {18446625}, issn = {0031-3025}, mesh = {Adult ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Carcinoma, Neuroendocrine/*pathology ; False Negative Reactions ; Female ; Humans ; Reproducibility of Results ; }, abstract = {BACKGROUND: Breast carcinoma is the most common malignancy in women worldwide. Though fine needle aspiration cytology (FNAC) plays an important role in preoperative diagnosis, there may be diagnostic delays in affected young women due to a lower index of suspicion.

METHODS: The files of the Departments of Pathology, Singapore General Hospital, Singapore, and Prince of Wales Hospital, Hong Kong, were searched for cases of breast carcinoma in women aged 35 years or less. Those with prior FNA procedures comprised our study group. The FNA smears were reviewed and classified into five categories: inadequate, benign, equivocal, suspicious, malignant. The findings were correlated with subsequent histology.

RESULTS: Thirty-four women aged 35 years and below underwent 35 FNACs, with one woman having bilateral FNA procedures. Upon review, one (2.9%) was classified as inadequate, one (2.9%) benign, five (14.3%) equivocal, five (14.3%) suspicious, 21 (60%) malignant and slides were not available for review for two (5.6%) cases. For six benign and equivocal cytological diagnoses, subsequent histology disclosed pure ductal carcinoma in situ (DCIS, 1 case), mucocoele-like lesions with DCIS (2 cases), invasive and in situ ductal carcinoma with neuroendocrine features (1 case) and two cases of invasive ductal carcinoma.

CONCLUSION: Diagnostic difficulties in cytological interpretation of aspirates from breast carcinoma in young women may lead to unwanted delays, which occurred in six (17.6%) of 34 women in our series. Low grade cancers posing a pitfall in cytological diagnosis have to be considered.}, } @article {pmid18442377, year = {2008}, author = {Myerson, JS and Nicum, S and Sharma, B and O'Brien, ME}, title = {Malignant mesothelioma with unexpected contralateral mediastinal shift: a case report.}, journal = {Journal of medical case reports}, volume = {2}, number = {}, pages = {125}, pmid = {18442377}, issn = {1752-1947}, abstract = {INTRODUCTION: Contralateral mediastinal shift due to pleural mesothelioma tissue, rather than a pleural effusion, is an unusual clinical feature of mesothelioma.

CASE PRESENTATION: A 63-year-old woman with a past history of treated invasive ductal carcinoma of the breast presented with breathlessness and chest pain. Her chest radiograph revealed contralateral mediastinal shift and drainage of over 3 litres of pleural fluid relieved her symptoms. She underwent further investigations which revealed pleural mesothelioma, rather than the expected metastatic breast cancer. When she represented with breathlessness a few months later, a chest radiograph again demonstrated contralateral mediastinal shift. A thoracic ultrasound on this occasion revealed only a small loculated pleural effusion and, unexpectedly, a large volume of malignant tissue, thereby explaining the chest radiograph appearances.

CONCLUSION: This case illustrates mediastinal shift away from the affected side which was caused by mesothelioma tissue itself, rather than by a pleural effusion which is the more usual cause of contralateral mediastinal shift in mesothelioma.}, } @article {pmid18441844, year = {2008}, author = {Lehman, JS and Benacci, JC}, title = {Cutaneous metastasis of invasive ductal carcinoma of the breast to an infusaport site.}, journal = {Cutis}, volume = {81}, number = {3}, pages = {223-226}, pmid = {18441844}, issn = {0011-4162}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; *Catheters, Indwelling ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Skin Neoplasms/*secondary ; Subclavian Vein ; }, abstract = {Cutaneous metastasis of a primary internal malignancy is a relatively common phenomenon, occurring in up to 10% of patients with noncutaneous cancer. Cutaneous metastasis can occur via direct extension, hematologic or lymphatic dissemination, or surgical implantation. The most common internal malignancy associated with the development of cutaneous metastases in females is breast cancer. We present a patient with widely metastatic invasive ductal carcinoma of the breast, status postpalliative mastectomy and chest wall coverage with a vertical rectus abdominus myocutaneous flap, who acquired cellulitis and, subsequently, noncontiguous cutaneous metastasis of her breast cancer to the site of her central venous access device (ie, infusaport). We hypothesize that the local inflammation associated with her recent bout of cellulitis and operations, in conjunction with the presence of a foreign body, may have predisposed the infusaport site to seeding by metastatic tumor cells. This case highlights the importance of considering cutaneous metastasis in the differential diagnosis of new skin eruptions in patients with cancer.}, } @article {pmid18439077, year = {2008}, author = {Ghaffari, SR and Sabokbar, T and Pour, PN and Dastan, J and Mehrkhani, F and Shoraka, S and Mohagheghi, MA and Tirgari, F and Mosavi-Jarrahi, A}, title = {Comparative genomic hybridization (CGH) analysis of chromosomal aberrations in Iranian patients with invasive ductal carcinoma breast cancer.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {9}, number = {1}, pages = {66-70}, pmid = {18439077}, issn = {2476-762X}, mesh = {Adult ; Aged ; Breast Neoplasms/epidemiology/*genetics/pathology ; Carcinoma, Ductal, Breast/epidemiology/*genetics/pathology ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 13/genetics ; Chromosomes, Human, Pair 17/genetics ; Chromosomes, Human, Pair 8/genetics ; Comparative Genomic Hybridization/*methods ; DNA, Neoplasm/genetics ; Female ; Humans ; Image Processing, Computer-Assisted ; In Situ Hybridization, Fluorescence ; Iran/epidemiology ; Lymphatic Metastasis ; Middle Aged ; Polymerase Chain Reaction ; Prognosis ; }, abstract = {INTRODUCTION: Breast cancer is one of the most common cancers in women; however, due to the complexity of chromosomal changes, limited data are available regarding chromosomal constitution.

MATERIALS AND METHODS: In this study, Comparative Genomic Hybridization (CGH) was used on 16 Iranian patients diagnosed with invasive ductal breast carcinomas.

RESULTS: 12 samples had abnormal CGH results (75%), including 21 types of chromosomal imbalance. The most prevalent were chromosomal gain of +1q, +17q, +8q and chromosomal loss of -13q. All three cases with DNA loss at chromosome 13q (-13q) had lymph node metastasis.

CONCLUSIONS: CGH is able to detect chromosomal abnormalities which are difficult to identify by conventional cytogenetic techniques. More studies on a larger sample size may help to confirm or rule out any possible correlation between 13q monosomy and lymph node metastasis, which could result in establishing new strategies for prevention and early detection of invasive breast tumors.}, } @article {pmid18437416, year = {2008}, author = {Turashvili, G and Hayes, M and Gilks, B and Watson, P and Aparicio, S}, title = {Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {452}, number = {6}, pages = {589-598}, pmid = {18437416}, issn = {0945-6317}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/classification/genetics/*pathology ; Carcinoma in Situ/pathology ; Epithelial Cells/*pathology ; Estrogen Receptor alpha/analysis ; Female ; Humans ; Immunohistochemistry ; Mammary Glands, Human/*pathology ; Mammography ; Precancerous Conditions/*pathology ; Receptors, Androgen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-alpha. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.}, } @article {pmid18432005, year = {2008}, author = {de Carsalade, GY and Receveur, MC and Ezzedine, K and Saget, J and Achirafi, A and Bobin, P and Malvy, D}, title = {[Delayed home screening of leprosy; experience of the screening team in Mayotte].}, journal = {Bulletin de la Societe de pathologie exotique (1990)}, volume = {101}, number = {1}, pages = {32-35}, pmid = {18432005}, issn = {0037-9085}, mesh = {Adolescent ; Adult ; Attitude to Health ; Child ; Comoros ; Contact Tracing ; Early Diagnosis ; Endemic Diseases ; *Family ; Female ; Health Education ; Humans ; Leprosy/*diagnosis/psychology/transmission ; Leprosy, Lepromatous/diagnosis ; Leprosy, Tuberculoid/diagnosis ; Male ; Mass Screening/*methods ; Middle Aged ; Self Care ; Self Concept ; }, abstract = {Mayotte, a French territory island located in the Indian Ocean near Madagascar, remains a leprosy endemic area. In 2006, leprosy was still a problem of public health with a prevalence of 3.94 per 10,000 inhabitants. There is practically no formal consensus about active screening (AS) on an index case. According to teams and their related staffs, the AS concerns intradomicilary contact individuals (IDC) restrictively or extended to extra-domicilary social and professional contacts. Date, number and frequency of these investigations depend on each team. Between 1997 and 2003, there was no AS planned in Mayotte, but all index case individuals have been encouraged to propose a screening to their relatives through specific campaign information and education. This procedure allowed to identify 10 new cases of leprosy infection among the IDC. Concurrently 12 IDC cases have been diagnosed by health workers. In 2003, we performed a postponed AS within IDC of every Mahorais case registered by passive detection between 1997 and 2003. 325 IDC have been examined and 15 new cases have been detected. All these new cases showed early leprosy features: 14 were paucibacillary forms, among which 9 cases with an isolated cutaneous lesion (7 had an infracentimetric lesion). One patient had multibacillary disease although he presented with an isolated skin lesion which developed within the 6 previous months. None presented with disability. Our results suggest that passive detection even reinforced by repeated individual information and education about leprosy is neither appropriate nor effective. The postponed AS seems to favour an increased self-esteem and a better involvement of the index patient in sanitary education together with the screening of his relatives. In the Mayotte background, the postponed AS has not been associated with a significant delay for diagnosis. Although WHO recommandations are to abandon immediate AS of IDC and to promote self-screening for leprosy our study suggests an intermediate position, namely delayed active screening for an enhanced effective detection.}, } @article {pmid18429832, year = {2008}, author = {Yasuhara, Y and Mikami, Y and Ishiguro, S}, title = {Metastatic breast carcinoma identified in a uterine leiomyosarcoma.}, journal = {Pathology international}, volume = {58}, number = {5}, pages = {317-321}, doi = {10.1111/j.1440-1827.2008.02230.x}, pmid = {18429832}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*secondary/therapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; Humans ; Hysterectomy ; Leiomyosarcoma/chemistry/*pathology/surgery ; Liver Neoplasms/secondary ; Middle Aged ; Neoplasm Metastasis ; *Neoplasms, Second Primary ; Uterine Neoplasms/chemistry/*pathology/*secondary/surgery ; }, abstract = {A rare example is described of an advanced invasive ductal carcinoma of the breast with concomitant metastatic foci in a uterine leiomyosarcoma. Both tumors arose in a 48-year-old woman, without any evidence of distant metastases as assessed on imaging at the time of diagnosis. The double diagnosis in this particular case was established on a combination of microscopic appearance of the uterine tumors in the hysterectomy specimen, immunophenotype assessment, and clinical information on the breast carcinoma. But the association between the two malignancies can be challenging and potentially difficult to prove.}, } @article {pmid18429827, year = {2008}, author = {Hasegawa, M and Moritani, S and Murakumo, Y and Sato, T and Hagiwara, S and Suzuki, C and Mii, S and Jijiwa, M and Enomoto, A and Asai, N and Ichihara, S and Takahashi, M}, title = {CD109 expression in basal-like breast carcinoma.}, journal = {Pathology international}, volume = {58}, number = {5}, pages = {288-294}, doi = {10.1111/j.1440-1827.2008.02225.x}, pmid = {18429827}, issn = {1440-1827}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, CD/*metabolism ; Antigens, Neoplasm/*metabolism ; Biomarkers, Tumor/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Fluorescent Antibody Technique, Indirect ; GPI-Linked Proteins ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Proteins/*metabolism ; }, abstract = {Breast cancer can be classified into several subtypes based on gene expression profiling. Basal-like breast carcinoma (BLC) has a triple negative phenotype, that is, the subtype lacks the estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). It has been recently reported that CD109, a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, is a new breast myoepithelial marker. In the present study CD109 expression was investigated in invasive ductal carcinomas (IDC) of the breast on immunohistochemistry. Eighty-eight formalin-fixed, paraffin-embedded breast carcinoma sections were immunostained with anti-CD109, anti-cytokeratin 5/6 (CK5/6), anti-calponin, anti-vimentin and anti-p63 antibodies. CD109 expression was detected in 18 of 30 basal-like breast carcinomas (BLC) but not in other types of 53 IDC (non-BLC) that were positive for ER, PgR and/or HER2. The percentage of CD109-positive tissues (60%) in BLC was similar to that of CK5/6 (63%) and higher than that of other myoepithelial markers including p63 (23%), calponin (33%) and vimentin (33%). Statistical analysis indicated that the CD109-positive group in BLC, but not the CK5/6-positive group in BLC, was associated with reduced fat invasion (P < 0.05). These findings indicate that CD109 is a useful diagnostic marker for BLC and that CD109 expression may affect biological properties of cancer cells.}, } @article {pmid18426675, year = {2008}, author = {Liu, YY and Fan, HH and Ren, YN and Yang, J and Nie, XX and Zhao, LH and Lin, JJ}, title = {[Immune tolerance induced by exosomes derived from regulatory dendritic cells of mice].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {16}, number = {2}, pages = {406-410}, pmid = {18426675}, issn = {1009-2137}, mesh = {Animals ; Dendritic Cells/cytology/*immunology/*transplantation ; Exosomes/immunology/*transplantation ; Female ; Graft Enhancement, Immunologic/*methods ; Graft Survival ; Immune Tolerance/*immunology ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Skin Transplantation ; Transplantation Immunology ; Transplantation, Homologous ; }, abstract = {The study was aimed to explore the roles of exosomes derived from regulatory dendritic cells of mice in the induction of immune tolerance. Immature DC (iDC) from mouse bone marrow cells and regulatory DCs (rDC) were induced by treating iDC with TGF-beta1 and IL-10. The phenotype of regulatory DCs and normal DCs were assayed by flow cytometry. Exosomes from immature DCs (iDex) and regulatory DCs (rDex) were isolated by ultracentrifugation and ultrafiltration. A skin transplantation model was established with the recipients BALB/c mice and the donor C57BL/6 mice. Recipients were divided into PBS control group, iDex group (injection 10 microg iDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation), rDex group (injection 10 microg rDex of donor C57BL/6 mice via tail vein at days 7 and 3 before skin transplantation). The capacity of the donor mice and the unrelated allogeneic donor mice to stimulate allogeneic T lymphocyte proliferation was examined by mixed lymphocyte culture (MLR). The results showed that TGF-beta1 and IL-10 could down-regulate the expressions of costimulatory molecules, including CD80, CD86 and CD40. The graft mean survival time (MST) in control group, iDex group and rDex group was 7.8, 10.7 and 18.8 days, respectively. There was significant difference in MST between iDex group and control group (p<0.05), and between rDex group and iDex group (p<0.01). The results of MLR assays indicated donor-specific hyporeactivity especially in rDex group, while the tolerant B/C mice were still immunocompetent to unrelated allogeneic DBA mouse. It is concluded that injection iDex or rDex of donor mice via tail vein before skin transplantation induces immunotolerance, and the effect of rDex is more significant.}, } @article {pmid18425387, year = {2008}, author = {Castellano, I and Sapino, A and Arisio, R and Viale, G and Bussolati, G and Bandelloni, R and Barresi, G and Bersiga, A and Bordi, C and Botti, G and Cosimi, F and D'Amore, E and Doglioni, C and Marchetti, A and Nappi, O and Romeo, F and Roncalli, M and Russo, R and Santinelli, A and Spagnoli, LG and Tanda, F and Tricomi, P and Trentini, G and Zanconati, F and Iurlaro, M}, title = {Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases.}, journal = {Oncology reports}, volume = {19}, number = {5}, pages = {1271-1275}, pmid = {18425387}, issn = {1021-335X}, mesh = {Female ; Genes, erbB-2/*genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mass Screening/methods ; Medical Oncology/methods ; Models, Statistical ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging/methods ; Receptor, ErbB-2/*biosynthesis ; Reproducibility of Results ; Time Factors ; }, abstract = {The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.}, } @article {pmid18425347, year = {2008}, author = {Calaf, GM and Echiburú-Chau, C and Zhao, YL and Hei, TK}, title = {BigH3 protein expression as a marker for breast cancer.}, journal = {International journal of molecular medicine}, volume = {21}, number = {5}, pages = {561-568}, pmid = {18425347}, issn = {1107-3756}, support = {NAG2 1637//PHS HHS/United States ; P30 ES 09089/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Extracellular Matrix Proteins/genetics/*metabolism ; Female ; Humans ; Mammary Glands, Human/cytology/metabolism/pathology ; Microarray Analysis ; Middle Aged ; Transforming Growth Factor beta/genetics/*metabolism ; }, abstract = {The current hypothesis of tumorigenesis in humans suggests that cancer cells acquire their hallmarks of malignancy through the accumulation of advantageous gene activation and inactivation events over long periods of time. For breast cancer development, this multistep process may manifest itself as a sequence of pathologically defined stages. It is widely held that breast cancer originates at the premalignant stage of atypical ductal hyperplasia, progresses to the preinvasive stage of ductal carcinoma in situ, and culminates in the potentially lethal stage of invasive ductal carcinoma. Tumor grade has been a highly valuable prognostic factor for breast cancer, and high-grade ductal carcinoma in situ lesions are associated with poor clinical outcome. The aim of this work was to investigate the BigH3 protein expression changes associated with various stages of breast cancer progression in comparison to benign specimens using tissue microarray technology. Pathological characteristics of breast tissues ranged from benign lesions to breast cancers either of lobular or ductal carcinomas in origin, and included in situ ductal carcinomas, lobular carcinomas, infiltrating ductal carcinomas, carcinomas, scirrhous carcinomas, adenocarcinomas and infiltrating colloid carcinomas. BigH3 protein expression was analyzed by immunohistochemistry in 192 cases of breast tumors. Results indicated a decrease in BigH3 protein expression from benign tissues to in situ ductal carcinoma, lobular carcinoma, infiltrating ductal carcinomas, carcinomas, scirrhous carcinoma, adenocarcinomas to infiltrating colloid carcinomas. We observed that the benign tissue had a 23-fold increase in BigH3 protein expression compared to the infiltrating colloid carcinoma which was the most malignant tissue analyzed. In summary, these studies confirmed the suppressor effect of the BigH3 gene expressed as protein expression in those processes related to the progression of breast tumorigenesis. We conclude that this protein can be used as a marker for breast cancer progression.}, } @article {pmid18419605, year = {2008}, author = {Cools, N and Van Tendeloo, VF and Smits, EL and Lenjou, M and Nijs, G and Van Bockstaele, DR and Berneman, ZN and Ponsaerts, P}, title = {Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells.}, journal = {Journal of cellular and molecular medicine}, volume = {12}, number = {2}, pages = {690-700}, pmid = {18419605}, issn = {1582-1838}, mesh = {CD4-Positive T-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology/*immunology ; Humans ; Immunomagnetic Separation ; Immunophenotyping ; *Immunosuppression Therapy ; Interleukin-10/*immunology ; Models, Immunological ; Monocytes/cytology ; T-Lymphocytes, Regulatory/*immunology ; Transforming Growth Factor beta/*immunology ; }, abstract = {Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.}, } @article {pmid18418235, year = {2008}, author = {Atmaca, Y and Duzen, V and Ozdol, C and Altin, T and Tulunay, C and Ertas, F and Erol, C}, title = {Total blush score: a new index for the assessment of microvascular perfusion in idiopathic dilated cardiomyopathy.}, journal = {Coronary artery disease}, volume = {19}, number = {3}, pages = {181-185}, doi = {10.1097/MCA.0b013e3282f35901}, pmid = {18418235}, issn = {0954-6928}, mesh = {Aged ; Cardiomyopathy, Dilated/*diagnostic imaging/*physiopathology ; Case-Control Studies ; Coronary Angiography/*methods ; Coronary Circulation/physiology ; Female ; Heart/physiopathology ; Humans ; Male ; Microcirculation/*diagnostic imaging/*physiopathology ; Middle Aged ; Ventricular Dysfunction, Left ; }, abstract = {BACKGROUND: The aim of this study was to evaluate tissue-level perfusion in patients with idiopathic dilated cardiomyopathy (IDC), using the myocardial blush grade technique.

METHOD: The study population consisted of 26 prospectively enrolled IDC patients (15 women and 11 men; mean age, 59+/-8.8 years) and 26 control subjects (11 women and 15 men; mean age, 54.9+/-10.6 years), whose angiographic films were technically adequate for myocardial blush grade analysis. After grading, we measured total blush score (TBS) for both groups. TBS was determined as the sum of the blush grades of each coronary territory.

RESULTS: A total of 156 coronary territories in both groups were assessed. Average of TBS was significantly lower in patients with IDC than in control group (7.6+/-1.2 vs. 8.8+/-0.4; P<0.0001). The TBS significantly and inversely correlated with New York Heart Association class, heart rate, left ventricular end-systolic dimension, and left ventricular end-diastolic pressure, and positively correlated with left ventricular ejection fraction (r=-0.76, P<0.001; r=-0.61, P=0.001; r=-0.77, P<0.0001; r=-0.68, P<0.0001; and r=0.67, P<0.0001, respectively).

CONCLUSION: In IDC, decreased TBS might be assumed to be a surrogate marker for a diseased microvascular network in the catheterization laboratory. The relationship between reduced TBS and IDC severity suggests that this index might have prognostic significance.}, } @article {pmid18417672, year = {2008}, author = {Chen, L and Fan, Y and Lang, RG and Guo, XJ and Sun, YL and Cui, LF and Liu, FF and Wei, J and Zhang, XM and Fu, L}, title = {Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases.}, journal = {International journal of surgical pathology}, volume = {16}, number = {2}, pages = {155-163}, doi = {10.1177/1066896907307047}, pmid = {18417672}, issn = {1066-8969}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/pathology ; Carcinoma, Papillary/chemistry/mortality/*pathology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Survival Rate ; }, abstract = {To study the clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma of breast (IMPC), 100 cases of invasive breast carcinoma with an IMPC component were reviewed. Compared with invasive ductal carcinoma, not otherwise specified, with similar histologic grades, carcinomas with IMPC were larger sized, had a higher lymph node metastasis rate with more nodes involved per case, and exhibited increased lymphovascular invasion. The presence of IMPC strongly correlated with the more aggressive behavior. No significant association was established between the proportion of the IMPC component and overall tumor size, histologic grade, lymph node metastasis rate, and distant metastasis, but a trend was noted. Long-term follow-up demonstrated a poorer 5-year and 10-year survival rate for patients with breast carcinoma containing an IMPC component. Breast carcinomas with micropapillary features are more aggressive tumors with a poorer prognosis. This specific structure should be carefully evaluated in the surgical pathology examination of breast carcinoma specimens.}, } @article {pmid18408445, year = {2008}, author = {Sugie, T and Nagai, T and Ohgaki, K}, title = {[A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {35}, number = {4}, pages = {683-686}, pmid = {18408445}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/*immunology/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*drug therapy/*immunology/metabolism/pathology ; Carcinoembryonic Antigen/blood ; Combined Modality Therapy ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Female ; Humans ; Immunotherapy ; Middle Aged ; Neoplasm Metastasis/diagnostic imaging/pathology ; Positron-Emission Tomography ; Radiography ; Receptor, ErbB-2/*immunology/*metabolism ; Tomography Scanners, X-Ray Computed ; Trastuzumab ; Gemcitabine ; }, abstract = {A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.}, } @article {pmid18407934, year = {2008}, author = {Ueda, S and Tsuda, H and Asakawa, H and Shigekawa, T and Fukatsu, K and Kondo, N and Yamamoto, M and Hama, Y and Tamura, K and Ishida, J and Abe, Y and Mochizuki, H}, title = {Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer.}, journal = {Japanese journal of clinical oncology}, volume = {38}, number = {4}, pages = {250-258}, doi = {10.1093/jjco/hyn019}, pmid = {18407934}, issn = {1465-3621}, mesh = {Adenocarcinoma, Mucinous/metabolism ; Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnostic imaging/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Intraductal, Noninfiltrating/metabolism ; Carcinoma, Lobular/metabolism ; Contrast Media ; Female ; Fluorodeoxyglucose F18/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; *Positron-Emission Tomography/methods ; Predictive Value of Tests ; Prognosis ; Radiopharmaceuticals/metabolism ; Receptor, ErbB-2/analysis ; Receptors, Estrogen ; Receptors, Progesterone/analysis ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer.

METHODS: Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC).

RESULTS: High SUV level was significantly correlated with tumor invasive size (< or = 2 cm) (P < 0.0001), higher score of nuclear grade (P < 0.0001), nuclear atypia (P < 0.0001) and mitosis counts (P < 0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P < 0.0001,< 0.0001, and < 0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P < 0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P < 0.0001).

CONCLUSIONS: High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pre-therapeutically predict biological characteristics and baseline risk of breast cancer.}, } @article {pmid18404368, year = {2009}, author = {Rakha, EA and Gill, MS and El-Sayed, ME and Khan, MM and Hodi, Z and Blamey, RW and Evans, AJ and Lee, AH and Ellis, IO}, title = {The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology.}, journal = {Breast cancer research and treatment}, volume = {114}, number = {2}, pages = {243-250}, doi = {10.1007/s10549-008-0007-4}, pmid = {18404368}, issn = {1573-7217}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; Carcinoma, Intraductal, Noninfiltrating/drug therapy/*pathology ; Carcinoma, Lobular/drug therapy/*pathology ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/diagnosis/drug therapy ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {UNLABELLED: Although invasive ductal (IDC) and lobular (ILC) breast carcinomas are well characterised in the literature, the biological and clinical significance of mixed tumours with both ductal and lobular components has not been investigated. In the current study, we have examined a well-characterised series of breast carcinoma with a long term follow-up that comprised 140 mixed tumours, 2170 IDC and 380 pure ILC.

RESULTS: Mixed tumours constituted 3.6% of all cases. The majority (59%) of the mixed tumours were grade 2 compared to 33% in IDC and 88% in ILC. Positive lymph nodes (LN) were found in 41% and definite vascular invasion (VI) in 26% of the cases. DCIS was detected in 123 (89%) and LCIS in 43 (31%) (both DCIS and LCIS were found in 39 cases). The majority of tumours were predominantly (>50 of tumour area) of ductal type (57%). When compared to pure IDC, mixed tumours showed an association with lower grade, ER positivity and lower frequency of development of distant metastases. When compared to pure ILC, mixed tumours showed an association with higher grade, positive LN metastasis, VI and development of regional metastasis. After adjustment for grade most of these differences were no longer apparent. There was an association between histologic type of carcinoma in LN metastasis and the predominant histologic type of the primary tumour. Mixed tumours showed metastatic patterns similar to that of ILC with frequent metastasis to bone. No clinically meaningful differences in survival were found between these mixed carcinomas and pure IDC or ILC of the breast or between mixed tumours with predominantly ductal or lobular phenotype.}, } @article {pmid18394457, year = {2008}, author = {Friedberg, MK and Roche, SL and Balasingam, M and Stephenson, E and Slorach, C and Fackoury, C and Kantor, PF}, title = {Evaluation of mechanical dyssynchrony in children with idiopathic dilated cardiomyopathy and associated clinical outcomes.}, journal = {The American journal of cardiology}, volume = {101}, number = {8}, pages = {1191-1195}, doi = {10.1016/j.amjcard.2007.12.017}, pmid = {18394457}, issn = {0002-9149}, mesh = {Adolescent ; Cardiomyopathy, Dilated/diagnostic imaging/mortality/*physiopathology/surgery ; Case-Control Studies ; Child ; Child, Preschool ; Echocardiography, Doppler ; Female ; Heart Transplantation ; Heart Ventricles/diagnostic imaging ; Humans ; Infant ; Male ; Retrospective Studies ; Stroke Volume/physiology ; Survival Analysis ; Systole/physiology ; Ventricular Dysfunction, Left/diagnostic imaging/*physiopathology ; }, abstract = {We studied mechanical dyssynchrony and its association with clinical status in children with idiopathic dilated cardiomyopathy (IDC). The SD of QRS to peak systolic velocity interval by tissue Doppler was measured in 12 left ventricular segments, as a dyssynchrony index (DI), in each child with IDC during a 12-month period. Results were compared with a control cohort. We used the adult-defined DI cutpoint of 32.6 ms to define patients with IDC as "dyssynchronous" or "synchronous" and compared clinical status and outcomes (transplantation listing/death) between these groups. Patients with IDC (n = 23) and controls (n = 14) had similar age, gender, and QRS duration. Patients with IDC had a higher DI than controls (44.8 +/- 23.7 vs 19.9 +/- 8 ms, p <0.0001). A DI >32.6 ms defined mechanical dyssynchrony in 65% of patients with IDC. Dyssynchronous and synchronous patients had similar QRS durations. Age at diagnosis, at dyssynchrony evaluation, and duration of clinical illness were similar in the 2 groups. New York Heart Association score was better in dyssynchronous than in synchronous patients (2 vs 3.1, p <0.05). Number of synchronous and dyssynchronous patients reaching the end point of death or transplantation was similar, although synchronous patients had poorer actuarial survival from the time of diagnosis (hazard ratio 3.25, p = .04). In conclusion, left ventricular mechanical dyssynchrony is prevalent in pediatric IDC. QRS duration alone is inadequate to define dyssynchrony in pediatric IDC, whereas the adult-derived DI of >32.6 ms seems applicable to the pediatric population. In this cohort, the presence of mechanical dyssynchrony was not associated with more severe clinical status or adverse outcomes.}, } @article {pmid18394338, year = {2008}, author = {Tu, SF and Guo, KY and Hu, LS and Mei, JZ and Zhou, J and Sun, M}, title = {[Expression of NKG2D ligands on dendritic cells at different development stages and its effect on cytotoxicity of NK cells].}, journal = {Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology}, volume = {24}, number = {4}, pages = {341-3, 347}, pmid = {18394338}, issn = {1007-8738}, mesh = {Antibodies/immunology/pharmacology ; Cells, Cultured ; Cytotoxicity, Immunologic/drug effects ; Dendritic Cells/*metabolism/ultrastructure ; Flow Cytometry ; GPI-Linked Proteins ; Gene Expression Regulation, Developmental/drug effects ; Histocompatibility Antigens Class I/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Killer Cells, Natural/*immunology/*metabolism ; Membrane Proteins/metabolism ; Microscopy, Electron, Transmission ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; }, abstract = {AIM: To investigate the expression of NKG2D ligands on dendritic cells(DC) at different development stages and its effect on cytotoxicity of natural killer(NK) cells.

METHODS: The monocytes were cultured into immature dendritic cells(iDC) and mature dendritic cells(mDC) with cytokines. NK cells were obtained from normal peripheral blood by CD56 antibody magnetic isolation.The expression of NKG2D ligands (MICA/B, ULBP1-3) was detected by flow cytometry. Cytotoxicity of NK cells and the NK cells blocked with anti-NKG2D mAbs against iDC and mDC was tested using LDH-releasing method.

RESULTS: IDC and mDC were of typical morphology and phenotypes. MICA, MICB, ULBP1, and ULBP3 were expressed on iDC and their expression rate was (32.39+/-8.30)%, (17.75+/-3.40)%, (26.71+/-6.48)%, (38.37+/-6.89)%, respectively. MICA and ULBP3 were expressed on mDC and their expression rate was (7.81+/-3.33)% and (8.36+/-2.42)%, respectively, which was lower than that on mDC (P<0.01). At the each E:T ratio cytotoxicity of NK cells against iDC was stronger than that against mDC (P<0.01). cytotoxicity of NK cells blocked with anti-NKG2D mAb against iDC was decreased compared with that of NK cells unblocked (P<0.05) while cytotoxicity of NK cells blocked with anti-NKG2D mAb against mDC showed no decrease compared with that of NK cells unblocked (P>0.05).

CONCLUSION: The expression of NKG2D ligands on iDC is higher than that on mDC, which plays an important role in the cytotoxic effect of NK cells against iDC, but has no effect on that against mDC. NKG2D-NKG2D ligands shows one of the molecular mechanisms that NK cells kill iDC selectively.}, } @article {pmid18392724, year = {2008}, author = {Shima, Y and Saisaka, Y and Furukita, Y and Nishimura, T and Horimi, T and Nakamura, T and Tanaka, K and Shibuya, Y and Ozaki, K and Fukui, Y and Hamada, M and Nishioka, Y and Okabayashi, T and Taniki, T and Morita, S and Iwata, J}, title = {Resected xanthogranulomatous pancreatitis.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {15}, number = {2}, pages = {240-242}, doi = {10.1007/s00534-007-1251-4}, pmid = {18392724}, issn = {0944-1166}, mesh = {Aged ; Histiocytes/pathology ; Humans ; Lymphocytes/pathology ; Male ; Pancreas/*pathology ; Pancreatitis/diagnosis/*pathology/*surgery ; Plasma Cells/pathology ; }, abstract = {Xanthogranulomatous changes in the pancreas are extremely rare. A 66-year-old man presented with a 2-year history of epigastralgia. Computed tomography scan revealed a 4-cm low-density area around the body of the pancreas. Magnetic resonance imaging demonstrated that the mass appeared hyperintense on a T2-weighted image and isointense on a T1-weighted image. Based on a diagnosis of invasive ductal carcinoma of the pancreas, distal pancreatectomy and splenectomy were performed. Sections examined from the mass showed an aggregation of many foamy histiocytes, lymphocytes, and plasma cells. The surrounding pancreatic tissue showed fibrosis and chronic inflammation. These findings suggested a xanthogranulomatous inflammation, and resulted in a diagnosis of xanthogranulomatous pancreatitis.}, } @article {pmid18390354, year = {2008}, author = {Hel-Or, Y and Shaked, D}, title = {A discriminative approach for wavelet denoising.}, journal = {IEEE transactions on image processing : a publication of the IEEE Signal Processing Society}, volume = {17}, number = {4}, pages = {443-457}, doi = {10.1109/TIP.2008.917204}, pmid = {18390354}, issn = {1057-7149}, mesh = {*Algorithms ; *Artifacts ; *Computer Graphics ; Discriminant Analysis ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Information Storage and Retrieval/methods ; Numerical Analysis, Computer-Assisted ; Reproducibility of Results ; Sensitivity and Specificity ; *Signal Processing, Computer-Assisted ; }, abstract = {This paper suggests a discriminative approach for wavelet denoising where a set of mapping functions (MFs) are applied to the transform coefficients in an attempt to produce a noise free image. As opposed to the descriptive approaches, modeling image or noise priors is not required here and the MFs are learned directly from an ensemble of example images using least-squares fitting. The suggested scheme generates a novel set of MFs that are essentially different from the traditional soft/hard thresholding in the over-complete case. These MFs are demonstrated to obtain comparable performance to the state-of-the-art denoising approaches. Additionally, this framework enables a seamless customization of the shrinkage operation to a new set of restoration problems that were not addressed previously with shrinkage techniques, such as deblurring, JPEG artifact removal, and various types of additive noise that are not necessarily Gaussian white noise.}, } @article {pmid18386126, year = {2008}, author = {Ballesio, L and Maggi, C and Savelli, S and Angeletti, M and De Felice, C and Meggiorini, ML and Manganaro, L and Porfiri, LM}, title = {Role of breast magnetic resonance imaging (MRI) in patients with unilateral nipple discharge: preliminary study.}, journal = {La Radiologia medica}, volume = {113}, number = {2}, pages = {249-264}, pmid = {18386126}, issn = {0033-8362}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast/*pathology ; Breast Diseases/diagnosis ; Breast Neoplasms/*diagnosis ; Breast Neoplasms, Male/diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Mammography ; Middle Aged ; Nipples/*metabolism ; Papilloma, Intraductal/diagnosis ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {PURPOSE: This study was performed to assess the role of magnetic resonance imaging (MRI) in patients with unilateral nipple discharge.

MATERIALS AND METHODS: Forty-four patients with bloody or serosanguineous nipple discharge and negative mammographic findings (35/44 cases) underwent MRI for evaluation of breast ducts. Ultrasonography, negative in 18 patients, identified 26 cases of ductal ectasia (12 simple, nine with solid intraductal echoes and wall thickening, five with inhomogeneous parenchyma). Galactography was negative in three patients and positive in nine. Nineteen patients were followed up by clinical examination, ultrasonography, and cytological evaluation of nipple discharge (6-12 months); three patients underwent excisional biopsy, ten core biopsy and 12 cytological biopsy (followed by excisional biopsy).

RESULTS: MRI identified 25 enhancing lesions Breast Imaging Reporting and Data Systems (BI-RADS) 3 or 4) and confirmed the galactographic findings (ductal ectasia, intraluminal filling defects). Five papillomatoses appeared as patchy, homogeneous enhancing areas, 15 intraductal papillomas as areas with well-defined margins and type II time-intensity curves, and two atypical ductal hyperplasias as diffuse nodular enhancement. One micropapillary ductal carcinoma in situ (DCIS), one papillary carcinoma and one infiltrating ductal carcinoma (IDC) were visualised as two segmental areas of enhancement and one mass-like enhancement with poorly defined margins (BI-RADS 4). The follow-up was negative, showing no pathological enhancement (BI-RADS 1) in 12 patients and benign enhancement (BI-RADS 2) in seven.

CONCLUSIONS: Breast MRI can be considered a valuable examination in the diagnosis of suspected ductal disease and an alternative to galactography when the latter cannot be used.}, } @article {pmid18383260, year = {2008}, author = {Chen, JH and Baek, HM and Nalcioglu, O and Su, MY}, title = {Estrogen receptor and breast MR imaging features: a correlation study.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {27}, number = {4}, pages = {825-833}, pmid = {18383260}, issn = {1053-1807}, support = {R01 CA90437/CA/NCI NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; R21 CA121568-01A2/CA/NCI NIH HHS/United States ; R01 CA127927/CA/NCI NIH HHS/United States ; R21 CA121568/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/chemistry/*diagnosis/pathology ; Carcinoma, Ductal, Breast/chemistry/*diagnosis/pathology ; Choline/analysis ; Female ; Humans ; Lymphatic Metastasis ; *Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Middle Aged ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/analysis ; }, abstract = {PURPOSE: To compare the MRI features between estrogen receptor (ER) positive and negative breast cancers.

MATERIALS AND METHODS: Breast MRI of 90 consecutive patients confirmed with invasive ductal carcinoma (IDC), 51 ER positive and 39 ER negative, were analyzed. The tumor morphology and dynamic contrast-enhanced (DCE) kinetics were evaluated based on the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon and compared. Enlarged axillary lymph nodes on MRI and choline (Cho) detection using MR spectroscopy (MRS) were also analyzed and compared. For patients receiving axillary node dissection the pathological nodal status was also compared.

RESULTS: ER negative breast cancer had bigger tumors compared to ER positive cancer (3.6 +/- 2.0 cm vs. 1.8 +/- 1.3 cm, P < 0.00005). ER negative cancer was more likely to exhibit nonmass type enhancements compared to ER positive cancer (P < 0.005). Enlarged axillary lymph nodes were more frequently identified on MRI in ER negative compared to ER positive patients (P < 0.05). After excluding patients undergoing neoadjuvant chemotherapy, auxiliary lymph node status did not show significant difference between ER positive and ER negative cancer on MRI and pathology. ER negative cancer was more likely to show the malignant type enhancement kinetics (P = 0.15), rim enhancement (P = 0.15), and Cho detection on MRS (P = 0.23) compared to ER positive cancer, but it did not reach a level of statistical significance.

CONCLUSION: ER negative breast cancer was more aggressive, with larger tumor size, more non-mass-type enhancement lesions, and a higher percentage showing enlarged axillary nodes on MRI. These features might be related to its poorer cellular differentiation and/or a higher angiogenesis.}, } @article {pmid18383208, year = {2008}, author = {Bettendorf, O and Schmidt, H and Staebler, A and Grobholz, R and Heinecke, A and Boecker, W and Hertle, L and Semjonow, A}, title = {Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1, and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate.}, journal = {Genes, chromosomes & cancer}, volume = {47}, number = {7}, pages = {565-572}, doi = {10.1002/gcc.20560}, pmid = {18383208}, issn = {1098-2264}, mesh = {Adenocarcinoma/genetics/metabolism/pathology ; Aged ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Chromosomal Instability ; Humans ; Immunoenzyme Techniques ; *Loss of Heterozygosity ; Male ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase/*metabolism ; Prognosis ; Prostatic Intraepithelial Neoplasia/genetics/metabolism/pathology ; Prostatic Neoplasms/*genetics/*metabolism/pathology ; Retinoblastoma Protein/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {Recent studies have shown that intraductal prostate carcinoma (IDC-P) should be considered as a separate lesion distinct from prostatic intraepithelial neoplasia (PIN). The purpose of the present study was to analyze the genetic relationship between benign prostatic tissue, PIN, invasive cancer, IDC-P, and extracapsular tumor tissue to get further information about the role of IDC-P in the development of prostate cancer. One hundred five radical prostatectomy specimens were investigated immunohistochemically, 77 cases were analyzed by PCR for LOH of the tumor suppressor genes TP53 and RB1, and 11 cases of IDC-P and 10 cases of PIN were investigated using comparative genomic hybridization (CGH). At CGH analysis, IDC-P showed several chromosomal imbalances in contrast to PIN, where no changes were found. We could demonstrate a significant increase of LOH for TP53 or RB1 from benign tissue to PIN. LOH of both TP53 and RB1 were frequently found in IDC-P (52%), followed by extracapsular tumor tissue (44%), invasive cancer (24%), PIN (19%), and benign prostatic tissue (17%). Increased immunohistochemical expression was found in invasive cancer for TP53, RB1, and for PTEN. Decreased expression could be demonstrated in extracapsular tumor tissue and in IDC-P. Our results indicate that IDC-P in general follows the genetic pathway from normal epithelium over PIN lesion. IDC-P represents a separate prostatic lesion and should be graded as a poorly differentiated carcinoma.}, } @article {pmid18382100, year = {2008}, author = {Seki, M and Ninomiya, E and Takano, K and Fujita, R and Aruga, A and Yamada, K and Tanaka, H and Matsueda, K and Mikami, K and Hiki, N and Saiura, A and Yamamoto, J and Yamaguchi, T and Yanagisawa, A and Ikeda, M and Sasaki, K and Kato, Y}, title = {Pancreatogram findings for carcinoma in situ (CIS) of the pancreas seen on endoscopic retrograde cholangiopancreatography and postoperative pancreatography of resected specimens: can CIS be diagnosed preoperatively?.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {8}, number = {2}, pages = {142-152}, doi = {10.1159/000123839}, pmid = {18382100}, issn = {1424-3911}, mesh = {Aged ; Aged, 80 and over ; Carcinoma in Situ/*diagnostic imaging/pathology/surgery ; *Cholangiopancreatography, Endoscopic Retrograde ; Female ; Humans ; Incidental Findings ; Male ; Middle Aged ; Pancreas/*diagnostic imaging ; Pancreatic Ducts/diagnostic imaging ; Pancreatic Neoplasms/*diagnostic imaging/pathology/surgery ; Postoperative Care ; Preoperative Care ; }, abstract = {BACKGROUND/AIMS: From 1992 to 2003, 7 carcinomata in situ (CIS) were incidentally discovered during microscopical observation of resected materials for advanced carcinomas of peripancreatic organs, of which 4 had undergone endoscopic retrograde cholangiopancreatography (ERCP) or postoperative pancreatography of the resected specimen (POP). In addition, 7 of 79 invasive ductal carcinomata (IDC) of the pancreas were accompanied by CIS > or =2 cm long. A total of 11 patients were reviewed here for pancreatographic findings for CIS of the pancreas.

METHODS: All resected pancreatobiliary materials were sliced serially at 5- to 8-mm intervals in a plane at right angles to the main pancreatic duct, referring to POP images.

RESULTS: Irregularity (I), non-continuous narrowing (N), granular defects (G), and dilatation (D) were seen in 78, 67, 33 and 22% on ERCP, respectively, and in 90, 70, 60 and 40% on POP, respectively.

CONCLUSIONS: I, N, G, and D are most important pancreatographic findings in ERCP and highly suggestive of CIS of the pancreas, so that whenever they are encountered, cytological and/or pathological examination of the pancreatic duct should be actively performed.}, } @article {pmid20063538, year = {2008}, author = {Yoney, A and Kucuk, A and Alan, O and Unsal, M}, title = {A retrospective study of treatment and outcome in 39 cases of male breast cancer.}, journal = {Hematology/oncology and stem cell therapy}, volume = {1}, number = {2}, pages = {98-105}, doi = {10.1016/s1658-3876(08)50041-0}, pmid = {20063538}, issn = {1658-3876}, mesh = {Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*mortality/pathology/*therapy ; Carcinoma/*mortality/pathology/*therapy ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Male ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Radiotherapy ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVES: Optimal management if male breast cancer (MBC) is not clearly established and treatment guidelines are scarce. We evaluated our own results in the treatment of male breast cancer patients with respect to local control (LC), overall survival (OS) and possible prognostic factors for survival.

PATIENTS AND METHODS: Thirty-nine patients with MBC were retrospectively studied to evaluate the results in this type of tumor; 94.8% had invasive ductal carcinoma (IDC), 2.6% invasive papillary carcinoma (IPC) and 2.6% invasive lobuler carcinoma (ILC). The distribution according to stage was 12.8%, 46.2%, 30.7% and 10.3% in Stages I, II, III and IV, respectively; 7.7% underwent radiotherapy (RT)+/-hormonotherapy (HT), 22.8% had chemotherapy (CT), 61.8% had chemoradiotherapy (CRT)+/-HT and 7.7% had HT in addition to surgery.

RESULTS: The distant metastases rate was 36% and the local recurrence rate was 5%. All the local recurrences and the distant metastases had occurred after the first two years. The 2-year disease free survival (DFS) and OS rates were 87.2% and 89.7%, respectively, and the 5-year DFS and OS rates were 65.8% and 80.1%, respectively. In a univariate analysis for OS, statistical significance was found for lymph node metastases (P=.00001), stage (P=.0098) and age (P=.03), while presence of RT in the treatment modality (P=.6849), and tumor size (P=.4439) demonstrated no significance. The presence of lymph node metastases significantly impaired OS (P=.004) and DFS (P=.014) in the multivariate analysis.

CONCLUSION: Postoperative radiotherapy was important in the management of MBC to improve LC resulting in one local failure, but did not improve OS and DFS. The presence of lymph node metastases significantly impaired OS and DFS.}, } @article {pmid18368323, year = {2008}, author = {Kijima, Y and Yoshinaka, H and Funasako, Y and Natsugoe, S and Aikou, T}, title = {Oncoplastic surgery after mammary reduction and mastopexy for bilateral breast cancer lesions: report of a case.}, journal = {Surgery today}, volume = {38}, number = {4}, pages = {335-339}, pmid = {18368323}, issn = {0941-1291}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/diagnosis/*surgery ; Carcinoma in Situ/diagnosis/*surgery ; Carcinoma, Ductal, Breast/diagnosis/*surgery ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*methods ; Mammography ; Mastectomy, Segmental/*methods ; Middle Aged ; Neoplasm Staging ; Patient Satisfaction ; Tomography, X-Ray Computed ; }, abstract = {We report a case of bilateral breast cancer lesions treated successfully by partial oncoplastic surgery. A 46-year-old Japanese woman presented with a small mass in the right breast. Mammography showed neither a mass nor calcification in the right breast; however, an irregular-shaped mass lesion was shown in the left breast. Ultrasonography and fine-needle aspiration biopsy revealed ductal carcinoma in situ in the inner-upper quadrant of the right breast and invasive ductal carcinoma in the outer-upper quadrant of the left breast. We considered that it would be difficult to obtain a good symmetrical outcome after partial mastectomy for the bilateral breast lesions because of the asymmetrical location of each lesion and her ptotic breasts. Thus, we performed bilateral partial resection, followed by an inferior pedicle reduction mammaplasty-type operation, with and without axillary lymphadenectomy, and achieved good cosmetic and oncologic results.}, } @article {pmid18365811, year = {2008}, author = {Michalopoulos, NV and Zagouri, F and Sergentanis, TN and Pararas, N and Koulocheri, D and Nonni, A and Filippakis, GM and Chatzipantelis, P and Bramis, J and Zografos, GC}, title = {Needle tract seeding after vacuum-assisted breast biopsy.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {49}, number = {3}, pages = {267-270}, doi = {10.1080/02841850701775030}, pmid = {18365811}, issn = {1600-0455}, mesh = {Biopsy, Needle/*adverse effects/instrumentation/methods ; Breast/*pathology/surgery ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/radiotherapy/surgery ; Female ; Guideline Adherence ; Humans ; Mastectomy ; *Neoplasm Seeding ; Time Factors ; Vacuum ; }, abstract = {BACKGROUND: A matter of substantial concern regarding all needle biopsy techniques is seeding along the biopsy needle tract.

PURPOSE: To assess cell seeding along the needle tract of vacuum-assisted breast biopsy (VABB).

MATERIAL AND METHODS: The study included 21 patients with ductal carcinoma in situ (DCIS) and 10 patients with invasive ductal carcinoma (IDC) diagnosed by VABB for nonpalpable mammographic lesions. VABB (11G, on a Fischer table) was performed, and the duration of the procedure was measured. After surgery, the whole needle tract was embedded in paraffin blocks, stained with hematoxylin-eosin, and examined by a pathologist.

RESULTS: Cases with dissemination of cancer cells in the needle tract were not observed (one-sided 97.5% CI 0-10.0%). In 2/31 (6.5%) cases (95% CI 0.8-21.4%), benign epithelial cell displacement was observed, and the duration of VABB was significantly longer in these two cases (52.5+/-3.5 min vs. 42.0+/-4.4 min for cases without benign cell displacement; P = 0.018, Mann-Whitney-Wilcoxon test for independent samples).

CONCLUSION: No displacement of malignant cells within the 11G needle tract was documented. Benign cell displacement was associated with longer VABB duration. The phenomenon of tumor cell dissemination along the needle tract is of questionable clinical significance when the treatment guidelines are followed.}, } @article {pmid18363570, year = {2008}, author = {Campbell, ID}, title = {Studies of focal adhesion assembly.}, journal = {Biochemical Society transactions}, volume = {36}, number = {Pt 2}, pages = {263-266}, doi = {10.1042/BST0360263}, pmid = {18363570}, issn = {0300-5127}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Cell Adhesion/physiology ; Contractile Proteins/*physiology ; DNA-Binding Proteins/*physiology ; Fibronectins/*physiology ; Filamins ; Humans ; Integrins/*physiology ; Microfilament Proteins/*physiology ; Models, Biological ; Phosphoproteins/*physiology ; Protein Binding ; Protein Conformation ; RNA-Binding Proteins/*physiology ; Talin/*physiology ; }, abstract = {Recent studies of some proteins involved in the formation of focal adhesions are described. These include fibronectin, integrins, talin, Dok1 and filamin. Emphasis is placed on features that facilitate regulated assembly of complexes; these include a modular construction and flexible regions that provide interaction sites whose affinity can be adjusted by conformational masking and phosphorylation.}, } @article {pmid18362854, year = {2008}, author = {Tajima, Y and Kuroki, T and Ohno, T and Furui, J and Tsuneoka, N and Adachi, T and Mishima, T and Kosaka, T and Haraguchi, M and Kanematsu, T}, title = {Resectable carcinoma developing in the remnant pancreas 3 years after pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {36}, number = {3}, pages = {324-327}, doi = {10.1097/MPA.0b013e318156adae}, pmid = {18362854}, issn = {1536-4828}, mesh = {CA-19-9 Antigen/blood ; Carcinoma, Pancreatic Ductal/blood/*pathology/*surgery ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/blood/diagnosis/*pathology/*surgery ; Pancreatic Neoplasms/blood/*pathology/*surgery ; Pancreaticoduodenectomy ; Pylorus/surgery ; Time Factors ; }, } @article {pmid18358477, year = {2008}, author = {Caliskan, M and Erdogan, D and Gullu, H and Muderrisoglu, H}, title = {Higher serum gamma-glutamyltransferase levels are independently associated with impaired coronary microvascular function in patients with dilated cardiomyopathy.}, journal = {Atherosclerosis}, volume = {201}, number = {1}, pages = {163-167}, doi = {10.1016/j.atherosclerosis.2008.01.010}, pmid = {18358477}, issn = {1879-1484}, mesh = {Adult ; Aged ; C-Reactive Protein/metabolism ; Cardiomyopathy, Dilated/diagnostic imaging/*enzymology/*physiopathology ; Cohort Studies ; Echocardiography, Doppler ; Female ; Fractional Flow Reserve, Myocardial/*physiology ; Humans ; Male ; Microcirculation/*physiology ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Risk Factors ; gamma-Glutamyltransferase/*blood ; }, abstract = {BACKGROUND: Patients with idiopathic dilated cardiomyopathy (IDC) have impaired coronary flow reserve (CFR) and reduced CFR has been reported to be a poor prognostic indicator and independent predictor of subsequent cardiac events in patients with IDC. Serum gamma-glutamyltransferase (GGT) level is an independent risk factor for cardiovascular disease. Therefore, we aimed to determine whether serum GGT level is associated with CFR impairment in patients with IDC.

METHODS: We examined 32 patients with IDC. The patients were divided into two groups based on serum GGT levels.

RESULTS: There were no significant differences between the lower and higher GGT groups regarding clinical data, baseline hemodynamics, medications and biochemical data except GGT and hsCRP levels. Subjects with higher GGT had significantly impaired CFR as compared to those with lower GGT (1.86+/-0.28 vs. 2.27+/-0.38, P=0.002). After adjusting for potential confounders, including age, sex, body mass index, blood pressure, lipids and glucose, we found that serum GGT levels were independently associated with CFR impairment (beta=-0.48, P=0.001). We also found that GGT level was a good predictor of low CFR at the receiver-operating characteristic curve. Area under the curve was 81% (95% CI: 0.66-0.95), and GGT level was significantly predictive of low CFR (P=0.003).

CONCLUSION: These results showed that there was an independent association between serum GGT level and CFR in patients with IDC.}, } @article {pmid18354176, year = {2008}, author = {Santegoets, SJ and Bontkes, HJ and Stam, AG and Bhoelan, F and Ruizendaal, JJ and van den Eertwegh, AJ and Hooijberg, E and Scheper, RJ and de Gruijl, TD}, title = {Inducing antitumor T cell immunity: comparative functional analysis of interstitial versus Langerhans dendritic cells in a human cell line model.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {180}, number = {7}, pages = {4540-4549}, doi = {10.4049/jimmunol.180.7.4540}, pmid = {18354176}, issn = {0022-1767}, mesh = {Cell Line ; Cell Movement ; Cytokines/metabolism ; Dendritic Cells/cytology/*immunology/metabolism ; HLA-A2 Antigen/immunology ; Humans ; Islets of Langerhans/cytology/*immunology/metabolism ; Lymph Nodes/cytology/immunology ; *Models, Immunological ; Neoplasms/*immunology ; Peptides/immunology ; Phenotype ; Skin/immunology ; T-Lymphocytes/*immunology ; }, abstract = {Dendritic cells (DC) are increasingly applied as a cellular adjuvant in immunotherapy of cancer. Two major myeloid DC subsets are recognized: interstitial DC (IDC) that infiltrate connective tissues and Langerhans cells (LC) that line epithelial surfaces. Yet, functional differences between IDC and LC remain to be defined. We recently showed that the CD34(+) acute myeloid leukemia cell line MUTZ-3 supports differentiation of both DC-SIGN(+) IDC and Langerin-positive Birbeck granule-expressing LC. By comparative functional characterization of MUTZ-3 IDC and MUTZ-3 LC, we aimed to elucidate the relative abilities of these two DC subsets to induce a specific T cell response and reveal the more suitable candidate for use as a clinical vehicle of tumor vaccines. Although mature LC and IDC displayed comparable lymph node-homing potential, mature LC showed higher allogeneic T cell stimulatory capacity. Nevertheless, IDC supported the induction of tumor Ag-specific CD8(+) T cells at an overall higher efficiency. This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15. Although this inability did not result in a detectable deviation in the cytokine expression profile of primed T cells, transduction with IL-12p70 significantly improved priming efficiency of LC, and ensured a functional equivalence with IDC in this regard. In conclusion, except for the inability of LC to release distinct type 1 T cell stimulatory cytokines, in vitro function of LC and IDC suggests comparable abilities of both subsets for the in vivo induction of antitumor T cells.}, } @article {pmid18350642, year = {2008}, author = {Hisa, T and Ohkubo, H and Shiozawa, S and Ishigame, H and Takamatsu, M and Furutake, M and Nobukawa, B and Suda, K}, title = {Growth process of small pancreatic carcinoma: a case report with imaging observation for 22 months.}, journal = {World journal of gastroenterology}, volume = {14}, number = {12}, pages = {1958-1960}, pmid = {18350642}, issn = {1007-9327}, mesh = {Adenocarcinoma/diagnosis/*diagnostic imaging/pathology/surgery ; Aged ; Carcinoma, Pancreatic Ductal/diagnosis/*diagnostic imaging/pathology/surgery ; Humans ; Male ; Pancreatic Neoplasms/diagnosis/*diagnostic imaging/pathology/surgery ; Prognosis ; Ultrasonography ; }, abstract = {This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.}, } @article {pmid18342452, year = {2008}, author = {Kaya, H and Bozkurt, SU and Erbarut, I and Djamgoz, MB}, title = {Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2 and p53 immunoexpression.}, journal = {Pathology, research and practice}, volume = {204}, number = {6}, pages = {367-371}, doi = {10.1016/j.prp.2008.01.012}, pmid = {18342452}, issn = {0344-0338}, mesh = {Adenocarcinoma/*metabolism/pathology ; Adult ; Aged ; Apocrine Glands/metabolism/pathology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carrier Proteins/metabolism ; Female ; Glycoproteins/metabolism ; Humans ; Immunoenzyme Techniques ; Membrane Transport Proteins ; Middle Aged ; Receptor, ErbB-2/*metabolism ; Receptors, Steroid/*metabolism ; Sweat Gland Neoplasms/*metabolism/pathology ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {The aims of this study were twofold: (i) to determine the occurrence frequency of apocrine carcinoma of the breast (ApBCa) in Turkish breast cancer (BCa) patients; and (ii) to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), gross cystic disease protein-15 (GCDFP-15), c-erbB-2, and p53 in these cases. Six hundred and twenty-six cases of BCa were studied immunohistochemically (streptoavidin-biotin horseradish peroxidase method). The results of ApBCa were compared with those of invasive ductal carcinoma not otherwise specified type (IDC-NOS) cases of similar grade. Thirteen cases of ApBCa were encountered, accounting for 2.1% of all BCa cases. Immunohistochemically, ApBCa positivity was as follows: GCDFP-15 (100%), ER (39%), PR (8%), AR (54%), p53 (39%), and c-erbB-2 (85%). In the IDC-NOS group, GCDFP-15* was expressed in less than 50% of the tumors. The occurrence frequencies of the other markers were as follows: ER (69%), PR (69%)*, AR (46%), c-erbB-2 (0%)*, and p53 (31%), (*) indicating significant differences between the two groups. For Turkish BCa patients, (i) the occurrence rate of ApBCa (2.1%) was high; and (ii) the following combination would allow for an immunohistochemical identification of ApBCa: GCDFP-15(+), c-erbB-2(+), and PR(-).}, } @article {pmid18338128, year = {2008}, author = {Tonegutti, M and Girardi, V}, title = {Stereotactic vacuum-assisted breast biopsy in 268 nonpalpable lesions.}, journal = {La Radiologia medica}, volume = {113}, number = {1}, pages = {65-75}, pmid = {18338128}, issn = {0033-8362}, mesh = {Adult ; Aged ; Biopsy, Needle/adverse effects/*methods/statistics & numerical data ; Breast Neoplasms/diagnostic imaging/*pathology ; Calcinosis/diagnostic imaging/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Mammary Glands, Human/pathology ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Reproducibility of Results ; *Stereotaxic Techniques/adverse effects/statistics & numerical data ; Vacuum ; }, abstract = {PURPOSE: We evaluated the reliability of stereotactic vacuum-assisted breast biopsies (VAB) from our personal experience.

MATERIALS AND METHODS: Between January 2003 and December 2005, 268 patients underwent VAB with an 11-gauge probe at our institution. Inclusion criteria were nonpalpable lesions, undetectable by ultrasound and suspected at mammography (microcalcifications, circumscribed mass, architectural distortion), for which cytology and/or core biopsy could not provide a definite diagnosis. Lesion mammographic patterns were microcalcifications in 186 cases (77.5%), mostly localised clusters (130/186: 70%); circumscribed mass with or without microcalcifications in 36 cases (15%) and architectural distortion with or without microcalcifications in 18 cases (7.5%). On the basis of the Breast Imaging Reporting and Data System (BI-RADS) classification, 16 cases (7%) were graded as highly suspicious for malignancy (BI-RADS 5), 81 (34%) as suspicious for malignancy (BI-RADS 4b), 97 (40%) as indeterminate (BI-RADS 4a) and 46 (19%) as probably benign (BI-RADS 3). Lesion size was 20 mm in only 38 cases (16%), 30 of which appeared as microcalcifications.

RESULTS: In 28/268 lesions (10.5%) the biopsy could not be performed (nonidentification of the lesion; inaccessibility due to location or breast size). In 12/240 (5%) biopsies, the sample was not representative. Pathology revealed 100/240 (42%) malignant or borderline lesions and 140/240 (58%) benign lesions. Among the malignant lesions, 16/100 (16%) were invasive carcinoma [infiltrating ductal carcinoma (IDC) or infiltrating lobular carcinoma (ILC)], 13/100 (13%) were microinvasive (T1mic), 35/100 (35%) were ductal carcinoma in situ (DCIS), 9/100 (9%) were lobular carcinoma in situ (CLIS). Among the borderline lesions, 27/100 (27%) were atypical epithelial hyperplasia [atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH)]. In 9/100 surgically treated lesions (9%), there was discordance between the microhistological findings of VAB and the pathological results of the surgical procedure: 8/9 were underestimated by VAB (four ADH vs. DCIS, three DCIS vs. IDC, one ADH vs. IDC), and 1/9 was overestimated (T1mic vs. DCIS). Complications following VAB occurred in 9/240 patients (3.7%).

CONCLUSIONS: In our experience, VAB showed fair reliability in the diagnosis of nonpalpable breast lesions despite a portion of failed (10.5%), nonsignificant (5%) procedures and underestimated lesions (9%).}, } @article {pmid18337623, year = {2007}, author = {Prasad, CP and Gupta, SD and Rath, G and Ralhan, R}, title = {Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression.}, journal = {Oncology}, volume = {73}, number = {1-2}, pages = {112-117}, doi = {10.1159/000120999}, pmid = {18337623}, issn = {1423-0232}, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cyclin D1/*metabolism ; Dishevelled Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phosphoproteins/*metabolism ; Signal Transduction ; Up-Regulation ; Wnt Proteins/*metabolism ; beta Catenin/*metabolism ; }, abstract = {OBJECTIVE: The Wnt/beta-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of beta-catenin and its downstream effector, cyclin D1, is implicated in malignant transformation and acquisition of an invasive tumor phenotype. This study aimed to determine the clinical significance of Wnt/beta-catenin canonical pathway components in breast cancer.

METHODS: Expression of beta-catenin, dishevelled (Dvl) and cyclin D1 was examined in invasive ductal carcinomas (IDCs) of the breast by immunohistochemical analysis.

RESULTS: Of the 98 IDCs analyzed, 30% of tumors displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed nuclear localization. Loss of cell surface beta-catenin was observed in 66% of breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1 overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed nuclear expression of beta-catenin, suggesting upregulation of the canonical Wnt/beta-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and beta-catenin (p < 0.01, OR = 15.8).

CONCLUSION: To our knowledge, this is the first study showing an association between nuclear localization of Dvl and beta-catenin in IDCs and suggests the upregulation of Wnt/beta-catenin pathway components, beta-catenin, Dvl and cyclin D1 in IDCs of the breast.}, } @article {pmid18329692, year = {2008}, author = {Hasebe, T and Imoto, S and Yokose, T and Ishii, G and Iwasaki, M and Wada, N}, title = {Histopathologic factors significantly associated with initial organ-specific metastasis by invasive ductal carcinoma of the breast: a prospective study.}, journal = {Human pathology}, volume = {39}, number = {5}, pages = {681-693}, doi = {10.1016/j.humpath.2007.09.012}, pmid = {18329692}, issn = {0046-8177}, mesh = {Adult ; Aged ; Bone Neoplasms/mortality/pathology/secondary ; Breast Neoplasms/mortality/*pathology/secondary ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology/secondary ; Chemotherapy, Adjuvant ; Female ; Fibrosis ; Humans ; Liver Neoplasms/mortality/pathology/secondary ; Lung Neoplasms/mortality/pathology/secondary ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis/pathology ; Prospective Studies ; }, abstract = {The purpose of this study was to identify histologic factors significantly associated with initial organ-specific metastasis by 1044 invasive ductal carcinomas (IDCs) of the breast with and without adjuvant therapy, separately, according to nodal status and pathologic TNM stage status. The following histologic factors were prospectively analyzed by multivariate analyses for distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy, and for distant organ metastasis, bone metastasis, liver metastasis, and lung metastasis in patients with IDC who received adjuvant therapy: (1) invasive tumor size, (2) histologic grade, (3) tumor necrosis, (4) fibrotic focus (FF), (5) lymphatic invasion, (6) blood vessel invasion, (7) adipose tissue invasion, (8) skin invasion, (9) muscle invasion, (10) age, (11) estrogen (ER)/progesterone (PR) status, and (12) nodal status. The results showed that FF diameter greater than 8 mm and FF fibrosis grade 1 were the factors that most accurately predicted distant organ metastasis and bone metastasis in patients with IDC who did not receive adjuvant therapy. In patients with IDC who received adjuvant therapy, FF diameter greater than 8 mm was the factor that most accurately predicted bone metastasis, and the presence of tumor necrosis and ER-/PR- were very important predictive factors for metastasis to the lung. Ten or more nodal metastases (N3) were the factor that most accurately predicted liver metastasis. Based on these findings, FF characteristics can be concluded to be the most important histologic factors for predicting metastasis to the bone, the presence of tumor necrosis and ER-/PR- for predicting metastasis to the lung, and N3 for predicting metastasis to the liver.}, } @article {pmid18326009, year = {2008}, author = {Korsching, E and Jeffrey, SS and Meinerz, W and Decker, T and Boecker, W and Buerger, H}, title = {Basal carcinoma of the breast revisited: an old entity with new interpretations.}, journal = {Journal of clinical pathology}, volume = {61}, number = {5}, pages = {553-560}, doi = {10.1136/jcp.2008.055475}, pmid = {18326009}, issn = {1472-4146}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*classification/metabolism/pathology ; Carcinoma, Basal Cell/*classification/metabolism/pathology ; Carcinoma, Ductal, Breast/*classification/metabolism/pathology ; Female ; Genotype ; Humans ; Immunophenotyping ; Keratins/metabolism ; Neoplastic Stem Cells/pathology ; }, abstract = {The introduction of global gene expression analysis in breast cancer research has focused attention onto a repeatedly described subgroup of invasive breast cancer, the basal-like carcinomas. This subgroup is characterised by the expression of high-molecular weight cytokeratins 5, 14 and 17; using immunohistochemical diagnosis, it represents approximately 7-20% of invasive breast cancers. Some of these tumours fulfil the criteria of grade 3 invasive ductal carcinoma, the so-called triple negative carcinomas. However, other rare subgroups of metaplastic, medullary and myoepithelial carcinomas also belong to this entity. Even though the initial clinical prognostic relevance of basal-like breast cancers may have been overestimated, its distinctive biology generates many questions regarding the pathogenesis, chemosensitivity and optimal clinical management of this subgroup. Physiological progenitor cells within the normal female breast share essential immunohistochemical features with basal-like breast cancers. Although the exact relationship between subgroups of normal breast cells and their respective malignant counterparts is still under investigation, the major hallmarks of physiological progenitor cells are either maintained or reactivated by distinct genetic changes in basal breast cancer cells. This review will discuss the impact of these findings on our global understanding of breast cancer pathogenesis, especially from the perspective of its potential histogenesis. Clinical consequences and potential future research directions driven by the definition of basal breast cancers will also be discussed.}, } @article {pmid18314615, year = {2007}, author = {Dietrich, D and Schuster, M and Lesche, R and Haedicke, W and Kristiansen, G}, title = {[Multiplexed methylation analysis--a new technology to analyse the methylation pattern of laser microdissected cells of normal breast tissue, DCIS and invasive ductal carcinoma of the breast].}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {91}, number = {}, pages = {197-207}, pmid = {18314615}, issn = {0070-4113}, mesh = {Breast/*cytology/physiology ; Breast Neoplasms/*genetics/*pathology ; *DNA Methylation ; DNA, Neoplasm/*genetics ; Dissection ; Female ; Gene Amplification ; Humans ; Polymerase Chain Reaction ; Reference Values ; }, abstract = {AIMS: DNA methylation has been shown to play an important role in breast cancer pathogenesis, but up until now it is not clear how the tissue components contribute to the overall methylation of the sample, because microdissection does not provide sufficient material for most standard methylation assays.

METHODS: We developed a technology to analyse several methylation markers in a limited number of cells dissected from tissue sections. To evaluate the technology, we analysed, among others, the methylation markers PITX2, RASSF1A and TFF1 in 79 samples of three PITX2 methylation positive invasive ductal carcinomas. The microdissected samples were from the invasive part, the intraductal part, the stroma, tumor infiltrating lymphocytes, chest wall muscle, adipose tissue and healthy ducts.

RESULTS: The multiplexed methylation analysis allows for the quantitative analysis of methylation patterns in microdissected samples with as few as 100 genome copies. In all analysed patients PITX2 and RASSF1A were highly methylated in invasive and intraductal carcinoma cells compared to other tissue components. TFF1 behaved inversely. PITX2 showed some methylation in normal adjacent breast tissue. The methylation of the individual markers varied little within one tissue type and between blocks.

CONCLUSIONS: This technology is a powerful tool to analyse the methylation of multiple markers in different microdissected tissue components. Methylation patterns may differ significantly between different markers and tissue components. This technology may help to analyse different transitions states of breast and other cancers.}, } @article {pmid18314479, year = {2008}, author = {Ricciardi, A and Elia, AR and Cappello, P and Puppo, M and Vanni, C and Fardin, P and Eva, A and Munroe, D and Wu, X and Giovarelli, M and Varesio, L}, title = {Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.}, journal = {Molecular cancer research : MCR}, volume = {6}, number = {2}, pages = {175-185}, doi = {10.1158/1541-7786.MCR-07-0391}, pmid = {18314479}, issn = {1541-7786}, support = {N01 CO 12400/CO/NCI NIH HHS/United States ; }, mesh = {Cell Hypoxia ; Cell Movement ; Chemokines/*genetics ; Dendritic Cells/*cytology/*metabolism ; *Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Receptors, Chemokine/*genetics ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues. Dendritic cells (DC) are professional antigen-presenting cells whose differentiation, migration, and activities are intrinsically linked to the microenvironment. DCs will home and migrate through pathologic tissues before reaching their final destination in the lymph node. We studied the differentiation of human monocytes into immature DCs (iDCs) in a hypoxic microenvironment. We generated iDC in vitro under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and examined the hypoxia-responsive element in the promoter, gene expression, and biochemical KEGG pathways. Hi-DCs had an interesting phenotype represented by up-regulation of genes associated with cell movement/migration. In addition, the Hi-DC cytokine/receptor pathway showed a dichotomy between down-regulated chemokines and up-regulated chemokine receptor mRNA expression. We showed that CCR3, CX3CR1, and CCR2 are hypoxia-inducible genes and that CCL18, CCL23, CCL26, CCL24, and CCL14 are inhibited by hypoxia. A strong chemotactic response to CCR2 and CXCR4 agonists distinguished Hi-DCs from iDCs at a functional level. The hypoxic microenvironment promotes the differentiation of Hi-DCs, which differs from iDCs for gene expression profile and function. The most prominent characteristic of Hi-DCs is the expression of a mobility/migratory rather than inflammatory phenotype. We speculate that Hi-DCs have the tendency to leave the hypoxic tissue and follow the chemokine gradient toward normoxic areas where they can mature and contribute to the inflammatory process.}, } @article {pmid18310280, year = {2008}, author = {Shibuya, R and Suzuki, T and Miki, Y and Yoshida, K and Moriya, T and Ono, K and Akahira, J and Ishida, T and Hirakawa, H and Evans, DB and Sasano, H}, title = {Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast.}, journal = {Endocrine-related cancer}, volume = {15}, number = {1}, pages = {113-124}, doi = {10.1677/ERC-07-0092}, pmid = {18310280}, issn = {1351-0088}, mesh = {17-Hydroxysteroid Dehydrogenases/genetics/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Aromatase/genetics/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Chromatography, Liquid ; Dihydrotestosterone/*metabolism ; Estradiol/*metabolism ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Middle Aged ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Spectrometry, Mass, Electrospray Ionization ; Steryl-Sulfatase/genetics/*metabolism ; Stromal Cells/metabolism/pathology ; Survival Rate ; }, abstract = {It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.}, } @article {pmid19565948, year = {2008}, author = {Shirley, SE and Mitchell, DI and Soares, DP and James, M and Escoffery, CT and Rhoden, AM and Wolff, C and Choy, L and Wilks, RJ}, title = {Clinicopathologic features of breast disease in Jamaica: findings of the Jamaican Breast Disease Study, 2000-2002.}, journal = {The West Indian medical journal}, volume = {57}, number = {2}, pages = {90-94}, pmid = {19565948}, issn = {0043-3144}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/epidemiology/*pathology ; Child ; Female ; Fibroadenoma/diagnosis/epidemiology/*pathology ; Fibrocystic Breast Disease/diagnosis/epidemiology/*pathology ; Hospitals, University/statistics & numerical data ; Humans ; Jamaica/epidemiology ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Sex Distribution ; Young Adult ; }, abstract = {OBJECTIVE: To describe the clinicopathologic profile of breast disease in Jamaica.

METHODS: The Jamaican Breast Disease Study is an ongoing prospective, multidisciplinary investigation of breast disease at the University Hospital of the West Indies (UHWI). The initial phase was a prevalence survey comprising all consenting patients referred to the Surgical Outpatient Department (SOPD) UHWI, for breast disease. Demographic, clinical, radiologic and pathologic information were recorded for each patient and the data for the first three years (2000-2002) were analyzed.

RESULTS: A total of 1189 patients was enrolled for the study period (28.8% of all new SOPD patients). The age range was 10 to 93 years (mean/SD = 36.5 +/- 16.4 years) with a female : male ratio of 14:1. Most patients (67.8%) presented with a palpable lump and the clinical diagnosis was benign in the majority (70.4%) of patients. Fibroadenoma was the most common benign histologic result (39.4% of all biopsies) followed by non-proliferative (fibrocystic) disease (19.3% of all biopsies). Proliferative disease without atypia, complex fibroadenoma and atypical ductal hyperplasia accounted for 6.9%, 2.6% and 0.4% of biopsies respectively. Overall, 23.4% of biopsies showed malignant histology (10.8% patients); invasive ductal carcinoma accounted for the majority of these cases (69.5%).

CONCLUSIONS: The majority of patients with breast disease in Jamaica are young women with clinically benign disease. There was a low prevalence of clinically significant premalignant disease. This is the first study to prospectively describe the clinicopathologic features of breast disease in Jamaica and supports the need for advocating breast cancer screening to facilitate detection of significant premalignant disease and early stages of breast cancer.}, } @article {pmid18306351, year = {2008}, author = {Itoh, H and Miyajima, Y and Umemura, S and Osamura, RY}, title = {Lower HER-2/chromosome enumeration probe 17 ratio in cytologic HER-2 fluorescence in situ hybridization for breast cancers: three-dimensional analysis of intranuclear localization of centromere 17 and HER-2 signals.}, journal = {Cancer}, volume = {114}, number = {2}, pages = {134-140}, doi = {10.1002/cncr.23367}, pmid = {18306351}, issn = {0008-543X}, mesh = {Breast Neoplasms/*genetics ; Carrier Proteins/genetics ; Cell Nucleus/genetics/metabolism ; Centromere/*genetics ; Chromosomes, Human, Pair 17/*genetics ; DNA Probes/*genetics ; Female ; Gene Amplification ; Humans ; *In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: Fluorescence in situ hybridization (FISH) is the gold standard for assessing HER-2 status for breast cancers, and paraffin-embedded tissue sections are used routinely for HER-2 FISH. Cytologic samples also are used, but to the authors' knowledge, little is known regarding the reliability of these samples. The objective of this study was to elucidate the usefulness of cytologic specimens for HER-2 FISH testing.

METHODS: Histologic and cytologic specimens from 32 patients with invasive ductal carcinoma of the breast were subjected to comparative analysis of HER-2 status by FISH. FISH was performed by using a PathVysion HER-2 DNA Probe Kit according the manufacturer's instructions. The signal ratios of chromosome enumeration probe 17 (CEP17) and HER-2 were estimated and compared. In 15 cytologic specimens, the distance between signals (HER-2 and CEP17) and the nearest nuclear membrane were measured by using 3-dimensional image analysis and confocal microscopy.

RESULTS: Cytologic and histologic FISH results were compared. Signal ratios of HER-2/CEP17 were lower in cytologic specimens from 26 of 32 patients compared with the histologic material. Three-dimensional image analysis demonstrated that the distance between the CEP17 signal and the nuclear membrane was shorter than the distance between the HER-2 gene and the nuclear membrane.

CONCLUSIONS: The current results demonstrated that CEP17 could be lost more easily through histologic sectioning compared with the cytology results, because CEP17 is closer to the nuclear membrane. FISH analysis in cytologic specimens produced more accurate HER-2/CEP17 ratios, because the whole nucleus was subjected to FISH testing, compared with matched histologic specimens.}, } @article {pmid18304901, year = {2008}, author = {Maalej, M and Hentati, D and Messai, T and Kochbati, L and El May, A and Mrad, K and Romdhane, KB and Ben Abdallah, M and Zouari, B}, title = {Breast cancer in Tunisia in 2004: a comparative clinical and epidemiological study.}, journal = {Bulletin du cancer}, volume = {95}, number = {2}, pages = {E5-9}, doi = {10.1684/bdc.2008.0584}, pmid = {18304901}, issn = {1769-6917}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; *Breast Neoplasms/epidemiology/pathology ; *Breast Neoplasms, Male/epidemiology/pathology ; Carcinoma in Situ/epidemiology/pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/pathology ; Carcinoma, Lobular/epidemiology/pathology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Sex Distribution ; Tunisia/epidemiology ; }, abstract = {The aim of this study was to determine the epidemiological, clinical and anatomopathological aspects of breast cancer in Tunisia. We censored and analyzed all cases of breast cancer newly diagnosed in Tunisia during the year 2004. During that year, 1437 new cases of invasive breast cancer were diagnosed and 35 cases of non invasive breast cancer. There were 1408 women and 29 men. The accrual incidence was 27.1 and the standardized incidence was 28.5. The mean age for women was 51 years. The mean tumour size was 40.8 mm (32.3 mm and 42.5 mm for private and public sectors respectively). Tumour stage was T1 in 12.2% cases, T2 in 46.9% cases, T3 in 11.2% cases and T4 in 24.7% cases. Invasive ductal carcinoma was the most frequent (86,6%) with SBR II grade representing 54.5%. 27.7% of the patients had undergone conservative treatment. There was an unexpected increase of the incidence since 1994 where the standardized incidence was 16.9. We have noticed a moderate decrease of the tumour size of 8 mm during the last decade. This national epidemiological study on breast cancer showed an increase in the incidence of this cancer with a moderate decrease in the clinical tumour size. The relative young mean age of our patients may be explained by the age distribution in our population or by risk factors that may be particular to our country.}, } @article {pmid18296827, year = {2008}, author = {Miura, K and Matsumori, A and Nasermoaddeli, A and Soyama, Y and Morikawa, Y and Sakurai, M and Kitabatake, A and Nagai, M and Inaba, Y and Nakagawa, H}, title = {Prognosis and prognostic factors in patients with idiopathic dilated cardiomyopathy in Japan.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {72}, number = {3}, pages = {343-348}, doi = {10.1253/circj.72.343}, pmid = {18296827}, issn = {1346-9843}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cardiomyopathy, Dilated/*mortality/*physiopathology ; Female ; Follow-Up Studies ; Health Surveys ; Heart Ventricles/pathology/physiopathology ; Humans ; Japan ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Sex Factors ; Stroke Volume/physiology ; Survival Rate ; }, abstract = {BACKGROUND: There have been few large-scale nationwide studies investigating both the prognosis and the prognostic factors of idiopathic dilated cardiomyopathy (IDC). A predictive score that can be used in clinical practice has not been established.

METHODS AND RESULTS: A nationwide epidemiological study of the prognosis of IDC was conducted in 1999 among randomly selected hospitals in Japan, and 147 departments participated in the present 5-year follow-up survey. The vital status of 1,554 IDC patients was collected in 2004 using medical records and residence-based registers. The crude 5-year survival rate for those diagnosed in 1998 was 78.6%. Cox's regression model selected 5 independent predictors of mortality: male sex, higher age, higher New York Heart Association functional class, higher left ventricular diameter index, and lower left ventricular ejection fraction. A predictive score using these 5 variables effectively predicted prognosis; 5-year survival rates were 90.6% in patients with a score of 4 or less and 49.0% in patients with a score of 9 or 10.

CONCLUSIONS: This nationwide survey revealed the present prognostic status of IDC in Japan and 5 independent predictors of prognosis that can be used in clinical practice as a predictive score.}, } @article {pmid18296077, year = {2008}, author = {Hussein, MR and Abd-Elwahed, SR and Abdulwahed, AR}, title = {Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast.}, journal = {Cell biology international}, volume = {32}, number = {6}, pages = {698-707}, doi = {10.1016/j.cellbi.2008.01.007}, pmid = {18296077}, issn = {1065-6995}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Neoplasm Invasiveness ; Proto-Oncogene Mas ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; }, abstract = {Estrogens are important for stimulating the growth of a large proportion of breast cancers. Progesterone plays critical roles in breast development and tumorigenesis. The c-erbB2 gene (HER-2/neu) is a proto-oncogene expressed in 10-34% of breast cancers. Its expression is associated with poor clinical outcome. The hypothesis that the progression of in situ ductal carcinoma of breast to invasive ductal carcinoma is associated with alterations of ER, PgR and HER-2/neu protein expression was tested. Of 100 mastectomy specimens examined, all contained both ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) not otherwise specified (NOS). The status of ER, PgR and HER-2/neu proteins was examined by immunochemistry. ER and PgR protein expression was scored as the mean value of positively stained cells. HER-2/neu protein expression was evaluated on ts staining pattern (0, 1+, 2+ and 3+). We found variations between DCIS and IDC with significant decrease of the mean values of ER and PgR positively stained cells in high-grade (Grade 3) IDC (ER: 49.2+/-10.3 vs. 30.8+/-5.5 and PgR: 40.0+/-10.0 vs. 22.3+/-5.1 in DCIS and IDC, respectively, P<0.05). Invasive carcinomas with lymph node metastases or lymphovascular invasion or both had lower mean values of ER and PgR positively stained cells compared to those without these features. In IDC (Grade 3), HER-2/neu protein expression values (1.2+/-0.2) were significantly high compared to DCIS (0.7+/-0.3, P<0.05). In addition, HER-2/neu protein expression values were significantly higher (P<0.05) in IDC with lymph node metastases or lymphovascular invasion (1.5+/-0.3) than those without these features (0.8+/-0.2). A significantly high mean (P<0.05) of ER and PgR positively stained cells was observed in postmenopausal females compared to premenopausal women. In contrast, high HER-2/neu expression values were seen only in premenopausal females. A significant positive correlation was observed between ER and PgR receptor expression (r=0.81). A low degree inverse correlation (r=-0.24, P<0.012) was found between ER+/PgR+ tumors and HER-2/neu expression. These findings substantiate the notion that breast cancer progression is often associated with alterations of ER, PgR and HER-2/neu expression. The underlying mechanisms of these alterations are open for further investigation.}, } @article {pmid18292984, year = {2008}, author = {Wang, J and McClean, PE and Lee, R and Goos, RJ and Helms, T}, title = {Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {116}, number = {6}, pages = {777-787}, pmid = {18292984}, issn = {0040-5752}, mesh = {Biomarkers ; *Breeding ; *Chromosome Mapping ; Chromosomes, Plant ; *Iron Deficiencies ; Minisatellite Repeats/*genetics ; Models, Genetic ; Plant Diseases/*genetics ; *Quantitative Trait Loci ; Soybeans/*genetics/*metabolism ; }, abstract = {Association mapping is an alternative to mapping in a biparental population. A key to successful association mapping is to avoid spurious associations by controlling for population structure. Confirming the marker/trait association in an independent population is necessary for the implementation of the marker in other genetic studies. Two independent soybean populations consisting of advanced breeding lines representing the diversity within maturity groups 00, 0, and I were screened in multi-site, replicated field trials to discover molecular markers associated with iron deficiency chlorosis (IDC), a major yield-limiting factor in soybean. Lines with extreme phenotypes were initially screened to identify simple sequence repeat (SSR) markers putatively associated with the IDC. Marker data collected from all lines were used to control for population structure and kinship relationships. Single factor analysis of variance (SFA) and mixed linear model (MLM) analyses were used to discover marker/trait associations. The MLM analyses, which include population structure, kinship or both factors, reduced the number of markers significantly associated with IDC by 50% compared with SFA. With the MLM approach, three markers were found to be associated with IDC in the first population. Two of these markers, Satt114 and Satt239, were also found to be associated with IDC in the second confirmation population. For both populations, those lines with the tolerance allele at both these two marker loci had significantly lower IDC scores than lines with one or no tolerant alleles.}, } @article {pmid18291614, year = {2008}, author = {Haraldsdóttir, KH and Ivarsson, K and Götberg, S and Ingvar, C and Stenram, U and Tranberg, KG}, title = {Interstitial laser thermotherapy (ILT) of breast cancer.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {34}, number = {7}, pages = {739-745}, doi = {10.1016/j.ejso.2008.01.008}, pmid = {18291614}, issn = {1532-2157}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*therapy ; Female ; Humans ; Hyperthermia, Induced/adverse effects/*methods ; Laser Therapy/adverse effects/*methods ; Middle Aged ; Pilot Projects ; Ultrasonography, Interventional ; }, abstract = {AIM: To find out if ILT can be used as radical treatment of breast cancer.

METHOD: Twenty-four patients, aged 39-84 (mean 61), with invasive breast cancer were treated with ILT. All underwent mammography, ultrasound and core biopsy before treatment. The tumour was an invasive ductal carcinoma in 15 patients, a lobular carcinoma in eight and lobular-ductal cancer in one. Average tumour diameter was 14 mm on ultrasound (5-35). Patients were treated in the outpatient clinics under local anaesthesia. Probes were placed under ultrasound guidance, in 19 patients, and ILT was performed with a diode laser at a steady-state temperature of 48 degrees C for 30 min using temperature feedback control. Standard surgical excision was performed 12 (4-23) days after ILT and was preceded by Doppler ultrasound.

RESULTS: Treatment-induced necrosis of invasive cancer was 33% (range 0-100) and was complete in three patients. At follow-up before surgery, the extent of laser damage could not be judged with ultrasound, although abolished tumour blood flow was demonstrated after treatment resulting in large necroses. Efficacy of treatment varied negatively with tumour size. The inefficacy of ILT was mainly due to the underestimation of tumour size by mammography and ultrasound and the shortcomings of these methods to demonstrate tumour borders, tumour irregularity and carcinoma in situ (CIS). ILT was well tolerated. Five patients had breast tenderness, and three patients had pain, during the first day after treatment. Small skin necroses were observed in two patients.

CONCLUSION: Small breast cancers can be treated radically with ILT. The method may become useful in the treatment of breast cancer but needs further refinement, even for small well-defined breast cancers, if it is going to be employed for radical treatment.}, } @article {pmid18290373, year = {2007}, author = {Kriuchkov, AN and Freĭnd, GG}, title = {[Age-related characteristics of breast invasive ductal carcinoma].}, journal = {Arkhiv patologii}, volume = {69}, number = {6}, pages = {15-17}, pmid = {18290373}, issn = {0004-1955}, mesh = {Adult ; Aged ; *Aging ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, abstract = {377 patients aged 30 to 79 years who had breast carcinoma were examined to study the age-related features of tumor anaplasia. The degree of tumor anaplasia was studied, in primary nodules, less and more than 2.5 cm in diameter in patients of different ages. This index decreased with age. This may explain more a malignant course of the disease in young patients.}, } @article {pmid18289638, year = {2008}, author = {Tang, P and Wang, J and Bourne, P}, title = {Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same?.}, journal = {Human pathology}, volume = {39}, number = {4}, pages = {506-513}, doi = {10.1016/j.humpath.2007.09.005}, pmid = {18289638}, issn = {0046-8177}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*classification/*pathology ; Carcinoma/*classification/*pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Prognosis ; Terminology as Topic ; }, abstract = {There are 4 major molecular classifications in the literature that divide breast carcinoma into basal and nonbasal subtypes, with basal subtypes associated with poor prognosis. Basal subtype is defined as positive for cytokeratin (CK) 5/6, CK14, and/or CK17 in CK classification; negative for ER, PR, and HER2 in triple negative (TN) classification; negative for ER and negative or positive for HER2 in ER/HER2 classification; and positive for CK5/6, CK14, CK17, and/or EGFR; and negative for ER, PR, and HER2 in CK/TN classification. These classifications use similar terminology but different definitions; it is critical to understand the precise relationship between them. We compared these 4 classifications in 195 breast carcinomas and found that (1) the rates of basal subtypes varied from 5% to 36% for ductal carcinoma in situ and 14% to 40% for invasive ductal carcinoma. (2) The rates of basal subtypes varied from 19% to 76% for HG carcinoma and 1% to 7% for NHG carcinoma. (3) The rates of basal subtypes were strongly associated with tumor grades (P < .001) in all classifications and associated with tumor types (in situ versus invasive ductal carcinomas) in TN (P < .001) and CK/TN classifications (P = .035). (4) These classifications were related but not interchangeable (kappa ranges from 0.140 to 0.658 for HG carcinoma and from 0.098 to 0.654 for NHG carcinoma). In conclusion, although these classifications all divide breast carcinoma into basal and nonbasal subtypes, they are not interchangeable. More studies are needed to evaluate to their values in predicting prognosis and guiding individualized therapy.}, } @article {pmid18286776, year = {2007}, author = {Ratnatunga, N and Liyanapathirana, LV}, title = {Hormone receptor expression and Her/2neu amplification in breast carcinoma in a cohort of Sri Lankans.}, journal = {The Ceylon medical journal}, volume = {52}, number = {4}, pages = {133-136}, doi = {10.4038/cmj.v52i4.916}, pmid = {18286776}, issn = {0009-0875}, mesh = {Adult ; Age Factors ; Breast Neoplasms/epidemiology/*genetics/pathology ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; Middle Aged ; Prevalence ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/*genetics/physiology ; Receptors, Progesterone/*genetics/physiology ; Retrospective Studies ; Sri Lanka/epidemiology ; }, abstract = {OBJECTIVE: 1) To determine the profile of estrogen and, progesterone receptors (ER, PR) expression and Her/2neu amplification in carcinoma of breast of Sri Lankan women. 2) To determine their inter-relationships, and associations with age at diagnosis and histological grade.

DESIGN: Retrospective analysis of data.

SETTING: Department of Pathology, Faculty of Medicine, University of Peradeniya.

MATERIALS: 124 samples of invasive ductal carcinoma of breast, stained for steroid receptors and Her/2neu amplification with immunohistochemistry.

MEASUREMENTS: 1) Semiquantative scores of steroid receptors and Her/2neu amplification. 2) Correlations of ER, PR, Her/2neu amplification, age at diagnosis and histological grade.

RESULTS: The prevalence of ER, PR and Her/2neu amplification were 53.2%, 50% and 14.6% respectively. The expression of ER and PR were significantly correlated (p < 0.001). and had a significant negative correlation with Her/2neu amplification (p0.003 each). Lower grade of the tumour was significantly related to the expression of ER (p0.000) and PR (p0.000) but not to Her/2neu amplification (p0.331). Age at diagnosis was significantly correlated to the expression of ER (p0.004), but not to PR (p0.365) or Her/2neu amplification (p0.456).

CONCLUSION: Prevalence or ER, PR and Her/2neu amplification in carcinoma of breast among Sri Lankans is similar to that described internationally. The correlations of ER, PR, Her/2neu amplification, to each other, age at diagnosis and grade of tumour is as reported in other countries.}, } @article {pmid18284499, year = {2008}, author = {Nogami, A and Sugiyasu, A and Tada, H and Kurosaki, K and Sakamaki, M and Kowase, S and Oginosawa, Y and Kubota, S and Usui, T and Naito, S}, title = {Changes in the isolated delayed component as an endpoint of catheter ablation in arrhythmogenic right ventricular cardiomyopathy: predictor for long-term success.}, journal = {Journal of cardiovascular electrophysiology}, volume = {19}, number = {7}, pages = {681-688}, doi = {10.1111/j.1540-8167.2008.01104.x}, pmid = {18284499}, issn = {1540-8167}, mesh = {Adult ; Aged ; Cardiomyopathies/*etiology/*surgery ; Catheter Ablation/*methods ; Electrocardiography/*methods ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Tachycardia, Ventricular/*complications/*surgery ; Treatment Outcome ; Ventricular Dysfunction, Right/*etiology/*surgery ; }, abstract = {INTRODUCTION: Although successful ablation of ventricular tachycardia (VT) is feasible in arrhythmogenic right ventricular cardiomyopathy (ARVC), long-term recurrence is common. The aim of this study was to assess the usefulness of a change in the isolated delayed component (IDC) as an endpoint of the catheter ablation in ARVC.

METHODS AND RESULTS: Eighteen patients (48 +/- 11 years) with ARVC were studied. Detailed endocardial mapping of the right ventricle (RV) was performed during sinus rhythm. IDCs were recorded in 16 patients and the latest IDCs were related to the VT circuit. Catheter ablation was carried out in the areas with the IDCs. At the end of the session, the IDC was electrically dissociated in one, disappeared in five, exhibited second-degree block in one, was significantly delayed (>or=50 ms) in three, and remained unchanged in six. The change in the IDC was correlated with the change in the type II/III late potentials in the signal-averaged electrocardiography (ECG) and the inducibility of the clinical VT after the ablation. During a follow-up of 61 +/- 38 months, VT recurred in six. The patients with a changed IDC had a significantly lower VT recurrence than those with no IDC or an unchanged IDC (P < 0.02).

CONCLUSION: In patients with ARVC, (1) the IDCs during sinus rhythm are related to the clinical VT and can be a target for the ablation, (2) a change in the IDC can be used as an endpoint, and (3) qualitative analyses of the serial signal-averaged ECGs may be useful for the long-term follow-up.}, } @article {pmid18280813, year = {2008}, author = {Golden, T and Aragon, IV and Rutland, B and Tucker, JA and Shevde, LA and Samant, RS and Zhou, G and Amable, L and Skarra, D and Honkanen, RE}, title = {Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer.}, journal = {Biochimica et biophysica acta}, volume = {1782}, number = {4}, pages = {259-270}, pmid = {18280813}, issn = {0006-3002}, support = {R01 CA060750/CA/NCI NIH HHS/United States ; P20 MD002314-01/MD/NIMHD NIH HHS/United States ; R01 CA060750-15/CA/NCI NIH HHS/United States ; CA-60750/CA/NCI NIH HHS/United States ; R01 CA060750-14S1/CA/NCI NIH HHS/United States ; P20 MD002314/MD/NIMHD NIH HHS/United States ; R01 CA060750-14/CA/NCI NIH HHS/United States ; P20 MD-002314/MD/NIMHD NIH HHS/United States ; C06 RR11174/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*enzymology ; Carcinoma, Ductal, Breast/*enzymology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology ; Cell Death ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Humans ; Mice ; Mice, Nude ; Nuclear Proteins ; Oxidative Stress ; Phosphoprotein Phosphatases ; Threonine ; Time Factors ; Ultraviolet Rays ; Up-Regulation ; Vinblastine/pharmacology ; }, abstract = {Ser/Thr protein phosphatase 5 (PP5) regulates several signaling-cascades that suppress growth and/or facilitate apoptosis in response to genomic stress. The expression of PP5 is responsive to hypoxia inducible factor-1 (HIF-1) and estrogen, which have both been linked to the progression of human breast cancer. Still, it is not clear if PP5 plays a role in the development of human cancer. Here, immunostaining of breast cancer tissue-microarrays (TMAs) revealed a positive correlation between PP5 over-expression and ductal carcinoma in situ (DCIS; P value 0.0028), invasive ductal carcinoma (IDC; P value 0.012) and IDC with metastases at the time of diagnosis (P value 0.0001). In a mouse xenograft model, the constitutive over-expression of PP5 was associated with an increase in the rate of tumor growth. In a MCF-7 cell culture model over-expression correlated with both an increase in the rate of proliferation and protection from cell death induced by oxidative stress, UVC-irradiation, adriamycin, and vinblastine. PP5 over-expression had no apparent effect on the sensitivity of MCF-7 cells to taxol or rapamycin. Western analysis of extracts from cells over-expressing PP5 revealed a decrease in the phosphorylation of known substrates for PP5. Together, these studies indicate that elevated levels of PP5 protein occur in human breast cancer and suggest that PP5 over-expression may aid tumor progression.}, } @article {pmid18271465, year = {2008}, author = {Menke-van der Houven van Oordt, CW and Fliervoet, HJ and Mandigers, CM and van Spronsen, DJ}, title = {[Cardiotoxicity of trastuzumab of significance in the adjuvant treatment of breast cancer].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {152}, number = {3}, pages = {158-163}, pmid = {18271465}, issn = {0028-2162}, mesh = {Adult ; Antibodies, Monoclonal/*adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*adverse effects/therapeutic use ; Breast Neoplasms/drug therapy ; Cardiomyopathies/*chemically induced ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Trastuzumab ; Ventricular Dysfunction, Left/*chemically induced ; }, abstract = {Three women aged 53, 52 and 36 years, respectively, underwent surgery for breast cancer, i.e. right-sided grade II invasive ductal carcinoma, left-sided grade III invasive ductal carcinoma, and left-sided multifocal grade III invasive ductal carcinoma, respectively. All 3 received adjuvant anthracycline-containing chemotherapy followed by trastuzumab. They developed significant cardiac dysfunction, as determined by a decrease in left ventricular ejection fraction (LVEF), which necessitated trastuzumab discontinuation. Trastuzumab therapy was resumed in the third patient after LVEF recovery but was stopped definitively when the LVEF decreased again. Trastuzumab has been shown to improve both disease-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, symptomatic cardiac failure due to cardiomyopathy has been observed in 0.6-4.1% of patients treated with trastuzumab after adjuvant anthracycline-based chemotherapy, whereas in 5-19% of the patients the decline in cardiac function led to permanent discontinuation of trastuzumab therapy. Cardiac function should be monitored regularly during trastuzumab therapy. An LVEF less than 50% or an absolute reduction of more than 10% warrant treatment discontinuation and close follow-up. Cardiac dysfunction is usually reversible; however, the long-term consequences of LVEF reduction following trastuzumab therapy are still unknown and warrant close attention, given the relatively young age and long life expectancy of these patients.}, } @article {pmid18265633, year = {2007}, author = {Kimura, W and Ma, J and Takeshita, A and Yamamoto, T and Moriya, T and Hirai, I and Fuse, A}, title = {Analysis of c-kit protein expression in pancreatic neoplasms and its implication for prognosis.}, journal = {Hepato-gastroenterology}, volume = {54}, number = {80}, pages = {2203-2208}, pmid = {18265633}, issn = {0172-6390}, mesh = {Adenocarcinoma/*metabolism/mortality/pathology ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Neoplasm Invasiveness ; Pancreas/metabolism ; Pancreatic Neoplasms/*metabolism/mortality/pathology ; Prognosis ; Proto-Oncogene Proteins c-kit/*metabolism ; }, abstract = {BACKGROUND/AIMS: To evaluate the expression and role of c-kit protein in the neoplasia of pancreatic neoplasms and its relationship to prognosis in invasive ductal carcinoma (IDC) of the pancreas.

METHODOLOGY: The immunohistochemical expression of c-kit protein was studied in normal pancreatic tissues, intraductal papillary-mucinous neoplasms of the pancreas (IPMN), mucinous cystic neoplasm of the pancreas (MCN), and IDC of the pancreas. The immunoreactive score (IRS) of c-kit protein expression was examined in normal pancreatic ductal cells, neoplastic cells, and pancreatic endocrine cells.

RESULTS: The IRS values of c-kit protein expression in various neoplastic cells were significantly higher than those in normal ductal cells. No significant difference was seen between IRS values of c-kit protein expression in various pancreatic neoplastic cells of IDC of the pancreas, IPMN and MCN. No significant difference was seen between IRS values of c-kit expression in endocrine cells among various pancreatic tissues. Furthermore, a survival analysis in patients with IDC of the pancreas showed an obvious trend toward decreased survival in patients with c-kit-positive cancer, and c-kit protein expression did not correlate with any clinicopathological factors in IDC of the pancreas.

CONCLUSIONS: c-kit protein expression may play an important role in neoplasia of pancreatic neoplasms. In view of the result that c-kit protein expression was found in 8% of IDC of the pancreas, a clinical trial for STI-571 (Glivec) against pancreatic cancer may be warranted for selected pancreatic cancer patients with c-kit protein expression.}, } @article {pmid18261627, year = {2008}, author = {Hasebe, T and Yamauchi, C and Iwasaki, M and Ishii, G and Wada, N and Imoto, S}, title = {Grading system for lymph vessel tumor emboli for prediction of the outcome of invasive ductal carcinoma of the breast.}, journal = {Human pathology}, volume = {39}, number = {3}, pages = {427-436}, doi = {10.1016/j.humpath.2007.07.016}, pmid = {18261627}, issn = {0046-8177}, mesh = {Adult ; Aged ; Apoptosis/physiology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Diagnostic Techniques and Procedures ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Lymphatic Vessels/*pathology ; Middle Aged ; Mitosis/physiology ; Neoplasm Recurrence, Local/pathology ; Neoplastic Cells, Circulating/*pathology ; Predictive Value of Tests ; Prognosis ; }, abstract = {There are no suitable histologic diagnostic clues for determining the true biological malignancy of invasive ductal carcinomas associated with lymph vessel tumor emboli. The purpose of this study was to devise a grading system for lymph vessel tumor emboli in invasive ductal carcinomas that would allow accurate prediction of the outcome of invasive ductal carcinoma patients with lymph vessel invasion. We classified 393 invasive ductal carcinomas into the following 4 grades according to the number of mitotic and apoptotic figures in tumor cells in lymph vessels at 1 high-power field: grade 0, no lymph vessel invasion; grade 1, absence of mitotic and apoptotic figures, presence of any number of mitotic figures and absence of apoptotic figures, or absence of mitotic figures and presence of any number of apoptotic figures; grade 2, 1 to 4 mitotic figures and 1 or more of apoptotic figures, or 1 or more of mitotic figures and 1 to 6 apoptotic figures; and grade 3, more than 4 mitotic figures and more than 6 apoptotic figures. The mortality rate increased with the grade, and the mortality rate of patients with grade 3 lymph vessel tumor emboli was more than 70%. Multivariate analyses with well-known prognostic factors demonstrated that grade 3 lymph vessel tumor emboli significantly increased the hazard rates for tumor recurrence, and tumor death independent of adjuvant therapy status, nodal status, or invasive tumor size. The grading system for lymph vessel tumor emboli is the best histologic grading system for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast.}, } @article {pmid18260729, year = {2007}, author = {Chariyalertsak, S and Purisa, W and Thisuphakorn, P and Karalak, A and Pakeetoot, T and Petmitr, S}, title = {Real-time quantitative PCR analysis of amplified DNA on chromosomes 4p15.2 and 6q23-24 from formalin-fixed, paraffin-embedded breast cancer tissues.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {8}, number = {4}, pages = {561-566}, pmid = {18260729}, issn = {2476-762X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Chromosome Aberrations ; Chromosomes, Human, Pair 4/*genetics ; Chromosomes, Human, Pair 6/*genetics ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Gene Amplification ; Humans ; Lymphatic Metastasis ; Middle Aged ; Paraffin Embedding ; Polymerase Chain Reaction/*methods ; Tissue Fixation ; }, abstract = {This study was performed to detect amplification of DNA sequences on chromosomes 4p15.2 and 6q23-24, obtained from formalin-fixed, paraffin-embedded, breast-cancer tissues. The prognostic relevance of the amplification was also demonstrated. DNA from formalin-fixed, paraffin-embedded tumor and corresponding normal tissues of 53 patients with breast cancer was extracted and amplified by real-time quantitative PCR technique. Amplification of the DNA sequences on chromosomes 4p15.2 and 6q23-24 was detected in 23 (43%) and 32 (60%) cases, respectively. Thirty-six (68%) cases showed amplification on both or one of the chromosomes. These frequencies are similar to that obtained from fresh samples in our previous study. In addition, amplification of the DNA on chromosomes 4p15.2 and / or 6q23-24 was predominantly observed in tumors with invasive ductal carcinoma. The findings in this study demonstrate that DNA extracted from formalin-fixed, paraffin-embedded breast tumors can be used to determine amplification of DNA sequences on selective chromosomal regions. We also suggest that the amplified DNA on chromosomal regions 4p15.2 and 6q23-24 might be involved in the development and progression of breast cancer.}, } @article {pmid18260722, year = {2007}, author = {Leong, BD and Chuah, JA and Kumar, VM and Yip, CH}, title = {Breast cancer in Sabah, Malaysia: a two year prospective study.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {8}, number = {4}, pages = {525-529}, pmid = {18260722}, issn = {2476-762X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Lobular/epidemiology/pathology ; Female ; Humans ; Incidence ; Malaysia/epidemiology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prospective Studies ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; Time Factors ; Young Adult ; }, abstract = {INTRODUCTION: Malaysian women have a 1 in 20 chance of developing breast cancer in their lifetime. Sabah, formerly known as North Borneo, is part of East Malaysia with a population of 3.39 million and more than 30 ethnic groups. We conducted a 2 year prospective epidemiological study to provide unreported data of breast cancer from this part of the world and to recognise which particular group of patients are more likely to present with advanced disease.

METHODS: All newly diagnosed breast cancers seen at the Queen Elizabeth Hospital, Kota Kinabalu, from January 2005 to December 2006 were included in the study. Patient and tumour characteristics, including age, race, education, socioeconomic background, parity, practice of breast feeding, hormonal medication intake, menopausal status, family history, mode of presentation, histology, grade, stage of disease and hormonal receptors status were collected and analysed.

RESULTS: A total of 186 patients were seen. The commonest age group was 40 to 49 years old (32.3%). Chinese was the commonest race (30.6%) followed by Kadazan-Dusun (24.2%). The commonest histology was invasive ductal carcinoma (88.4%). Stages at presentation were Stage 0- 4.8%, Stage I- 12.9%, Stage II- 30.1%, Stage III- 36.6% and Stage IV- 15.6%. The estrogen and progesterone receptor status was positive in 59.1% and 54.8% of cases, respectively. 73.7% of Chinese patients presented with early cancer compared to 36.4% of the other races. Patients who presented with advanced disease were also poor, non-educated and from rural areas. 20.4% of patients defaulted treatment; most of them opted for traditional alternatives.

CONCLUSIONS: Sabahan women with breast cancer present late. Great efforts are needed to improve public awareness of breast cancer, especially among those who have higher risk of presenting with advanced disease.}, } @article {pmid18256927, year = {2009}, author = {Subramaniam, MM and Chan, JY and Soong, R and Ito, K and Ito, Y and Yeoh, KG and Salto-Tellez, M and Putti, TC}, title = {RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression.}, journal = {Breast cancer research and treatment}, volume = {113}, number = {1}, pages = {113-121}, doi = {10.1007/s10549-008-9917-4}, pmid = {18256927}, issn = {1573-7217}, mesh = {Breast Neoplasms/*genetics/mortality/*pathology/surgery ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Core Binding Factor Alpha 3 Subunit/*antagonists & inhibitors/*genetics ; DNA Methylation ; DNA Primers ; DNA, Neoplasm/genetics ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Mastectomy ; Microdissection ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Polymerase Chain Reaction ; *Promoter Regions, Genetic ; }, abstract = {BACKGROUND: We had previously established that inactivation of RUNX3 occurs by frequent promoter hypermethylation and protein mislocalization in invasive ductal carcinomas (IDC) of breast. Here, we hypothesize that inactivation of RUNX3 occurring in ductal carcinoma in situ (DCIS) represent early event in breast carcinogenesis.

METHODS: The study cohort of 40 patients included 17 pure DCIS cases and 23 cases of DCIS with associated IDC (DCIS-IDC). The DCIS and IDC components of mixed cases were manually microdissected to permit separate evaluation. All the 63 samples including 17 pure DCIS, 23 samples each of DCIS and IDC of DCIS-IDC cases were analyzed for RUNX3 protein expression using R3-6E9 monoclonal antibody as well as promoter methylation status by methylation specific PCR.

RESULTS: Compared to matched normal breast samples (4 of 40, 10%), DCIS (35 of 40, 88%) and IDC (21 of 23, 91%) exhibited significant RUNX3 inactivation (P<0.001) in the form of negative or weak nuclear staining. In contrast to normal breast tissues (1/10, 10%), promoter hypermethylation of RUNX3 was significantly higher in the neoplastic breast samples (46 of total 61, 75%) including 30 of 40 (75%) DCIS and 16 of 21 (76%) IDC samples (P=0.009). Overall, promoter hypermethylation correlated with RUNX3 inactivation in 42 of 46 (91%) methylated samples (P=0.03). Mislocalized cytoplasmic expression also accounted for RUNX3 inactivation in majority of DCIS (33/40, 83%) and IDC (20/23, 87%) samples independent of promoter hypermethylation.

CONCLUSION: Our data suggest that RUNX3 inactivation by promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression.}, } @article {pmid18256205, year = {2008}, author = {Rahman, M and Lax, SF and Sutter, CH and Tran, QT and Stevens, GL and Emmert, GL and Russo, J and Santen, RJ and Sutter, TR}, title = {CYP1B1 is not a major determinant of the disposition of aromatase inhibitors in epithelial cells of invasive ductal carcinoma.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {36}, number = {5}, pages = {963-970}, pmid = {18256205}, issn = {1521-009X}, support = {R01 CA084456/CA/NCI NIH HHS/United States ; R01 CA084456-08/CA/NCI NIH HHS/United States ; ES 08148/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antibodies/metabolism ; Aromatase/*metabolism ; Aromatase Inhibitors/*pharmacology ; Aryl Hydrocarbon Hydroxylases ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cytochrome P-450 CYP1B1 ; Cytochrome P-450 Enzyme System/*metabolism ; Epithelial Cells/metabolism ; Humans ; Male ; Microsomes/drug effects/metabolism ; Rabbits ; }, abstract = {CYP1B1 and CYP19 (aromatase) have been shown to be expressed in breast tumors. Both enzymes are efficient estrogen hydroxylases, indicating the potential for overlapping substrate and inhibitor specificity. We measured the inhibition properties of aromatase inhibitors (AIs) against CYP1B1-catalyzed hydroxylation of 17beta-estradiol (E2) to determine whether CYP1B1 affects the disposition of AIs. In addition, we estimated the frequency of coexpression of these enzymes in breast tumor epithelium. Immunohistochemical analyses of CYP19 and CYP1B1 in a panel of 29 cases of invasive ductal carcinoma of the breast showed epithelial cell staining for CYP19 in 76% and for CYP1B1 in 97% of the samples. Statistical analysis showed no significant correlation (0.33) for positive expression of CYP19 and CYP1B1 (p > 0.07). CYP1B1 inhibition was determined for two steroidal inhibitors: formestane and exemestane and five nonsteroidal inhibitors: aminoglutethimide, fadrozole, anastrozole, letrozole, and vorozole. Of the seven compounds tested, only vorozole exhibited inhibition of CYP1B1 activity with IC(50) values of 17 and 21 microM for 4-hydroxy estradiol and 2-hydroxy estradiol, respectively. The estimated K(i) values of vorozole for E2 4- and 2-hydroxylation were 7.26 and 6.84 microM, respectively. Spectrophotometric studies showed that vorozole was a type II inhibitor of CYP1B1. This study shows that with the exception of vorozole, the aromatase inhibitors are selective for CYP19 relative to CYP1B1. Thus, although both CYP19 and CYP1B1 are expressed in a high percentage of breast cancers, CYP1B1 is not a major determinant of the disposition of AIs.}, } @article {pmid18248561, year = {2008}, author = {Tanaka, K and Imoto, S and Wada, N and Sakemura, N and Hasebe, K}, title = {Invasive apocrine carcinoma of the breast: clinicopathologic features of 57 patients.}, journal = {The breast journal}, volume = {14}, number = {2}, pages = {164-168}, doi = {10.1111/j.1524-4741.2007.00548.x}, pmid = {18248561}, issn = {1524-4741}, mesh = {Aged ; Apocrine Glands/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptors, Estrogen ; Receptors, Progesterone ; Survival Analysis ; }, abstract = {Apocrine carcinoma is a rare, unique, and morphologically distinctive type of invasive ductal carcinoma (IDC). The features of invasive apocrine carcinoma (IAC) and their possible prognostic implications have not been fully investigated. To this end, we examined the clinicopathologic characteristics and outcome of patients with IAC and compared these factors with those of patients with IDC. Out of 2,055 breast cancer patients who had undergone breast surgery between 1995 and 2005, 57 patients of IAC and 1,583 patients of IDC were analyzed. The mean ages of the patients with IAC and of those with IDC were 58.5 +/- 10.9 years and 54.4 +/- 11 years, respectively (p = 0.006). The percentages of patients with axillary nodal metastasis and lymphatic invasion were significantly lower in the IAC group than in the IDC group (p = 0.03 and 0.02, respectively). The percentage of estrogen and progesterone receptor negativity was higher in the IAC group than in the IDC group (p < 0.001). After a median follow-up period of 49 months (range, 1-133 months), seven (12%) patients with IAC and 244 (15%) patients with IDC had experienced recurrences. Three (5%) patients with IAC and 125 (8%) patients with IDC died of recurrent breast cancer. No significant differences in the relapse-free survival (p = 0.83) and overall survival (p = 0.75) rates were observed between the two groups. Although IAC and IDC have different clinicopathologic characteristics, the prognoses of patients with these diseases are similar.}, } @article {pmid18242371, year = {2008}, author = {Trigo Rocha, F and Gomes, CM and Mitre, AI and Arap, S and Srougi, M}, title = {A prospective study evaluating the efficacy of the artificial sphincter AMS 800 for the treatment of postradical prostatectomy urinary incontinence and the correlation between preoperative urodynamic and surgical outcomes.}, journal = {Urology}, volume = {71}, number = {1}, pages = {85-89}, doi = {10.1016/j.urology.2007.09.009}, pmid = {18242371}, issn = {1527-9995}, mesh = {Aged ; Humans ; Male ; Middle Aged ; Prospective Studies ; Prostatectomy/*adverse effects ; Quality of Life ; Treatment Outcome ; Urinary Incontinence/etiology/*physiopathology/*surgery ; *Urinary Sphincter, Artificial ; Urodynamics ; }, abstract = {OBJECTIVES: We have evaluated prospectively the long-term efficacy of the artificial urinary sphincter (AUS) AMS 800 for the treatment postradical prostatectomy urinary incontinence (PRPUI) patients. We also evaluated the correlation between preoperative urodynamic findings and surgical outcomes.

METHODS: From May 1997 to April 2003, 40 consecutive patients with PRPUI caused by intrinsic sphincter deficiency (ISD) were treated with the AMS 800. Mean age was 68.3 +/- 6.3 years. Continence status was evaluated on the basis of pad count, impact of urinary incontinence on the quality of life, complications, and surgical revisions. Preoperative urodynamic findings were correlated with surgical outcomes.

RESULTS: Follow-up ranged from 27 to 132 months (mean = 53.4 +/- 21.4 months). There was a significant reduction in pad count from 4.0 +/- 0.9 to 0.62 +/- 1.07 diapers per day (P <0.001) leading to continence in 90%. There was a significant reduction on the impact of incontinence decreasing from 5.0 +/- 0.7 to 1.4 +/- 0.93 (P <0.001) in a visual analogue scale (VAS). Surgical revision rate was 20%. Preoperative urodynamics was useful to identify sphincter deficiency. Except by a tendency of worse results in patients with reduced bladder compliance (RBC), other urodynamic parameters did not correlate with a worse surgical outcome.

CONCLUSIONS: The AMS 800 offers good long-term continence to most PRPUI patients. Preoperative findings like detrusor hyperactivity (DH), impaired detrusor contraction (IDC), low Valsalva leak point pressure, bladder outlet obstruction (BOO), and mild RBC were not associated with worse surgical outcomes.}, } @article {pmid18227734, year = {2008}, author = {El Sharkawy, SL and Farrag, AR}, title = {Mean nuclear area and metallothionein expression in ductal breast tumors: correlation with estrogen receptor status.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {16}, number = {2}, pages = {108-112}, doi = {10.1097/PAI.0b013e31806d9b88}, pmid = {18227734}, issn = {1541-2016}, mesh = {Breast Neoplasms/chemistry/*diagnosis/pathology ; Carcinoma, Ductal, Breast/chemistry/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/diagnosis/pathology ; Cell Nucleus/pathology ; Female ; Fibroadenoma/chemistry/diagnosis/pathology ; Humans ; Immunohistochemistry ; Metallothionein/*analysis ; Receptors, Estrogen/*analysis ; }, abstract = {Breast carcinoma is the most common malignancy in women. Estrogen is an important growth factor for breast tumor that plays an important role in regulating the proliferation and differentiation of normal and malignant mammary epithelial cells. Nuclear morphometry and metallothioneins (MTs) are indicators of proliferation that have been used as predictors of prognosis in many tumors. The present study aimed to study mean nuclear area (MNA) and MT; estrogen receptor (ER) expression in fibroadenoma (FA), ductal carcinoma in situ (DCIS), and infiltrating ductal carcinoma (IDC) of the breast. Also MNA and MT expression will be correlated with histologic grade and ER status in breast carcinoma. Breast tissues from 18 patients with FA, 10 patients with DCIS, and 40 patients with IDC were used in this study. MNA and MT expression; as proliferation markers; were investigated and correlated with ER status. All cases of FA, 7 out of 10 cases (70%) of DCIS and 23 out of 40 cases (57.5%) of IDC were positive for ER. MNA of cancer cells was significantly larger than that of normal and benign breast tissue. A significant direct correlation was found between MNA and histologic grades. MNA of ER-negative carcinomas was significantly larger than that of ER-positive tumors. In normal and benign breast tissue, myoepithelial cells consistently expressed the MT protein. Four out of 10 DCIS cases (40%) and 24 out of 40 cases of IDC cases (60%) were positively stained for MT. MT positivity was directly correlated with histologic grade of IDC. There was a highly significant inverse correlation between MT and ER overexpression. From this study, it is concluded that in invasive ductal carcinoma of the breast, the large MNA and MT overexpression are correlated with histologic grades and ER negativity. Therefore, large MNA and MT overexpression may be possible important indicators for more aggressive and less differentiated breast carcinoma.}, } @article {pmid18227005, year = {2008}, author = {Trabelsi, A and Rammeh, S and Stita, W and Mokni, M and Mourou, A and Korbi, S}, title = {[Detection of Epstein-Barr virus in breast cancers with lymphoid stroma].}, journal = {Annales de biologie clinique}, volume = {66}, number = {1}, pages = {59-62}, doi = {10.1684/abc.2008.0191}, pmid = {18227005}, issn = {0003-3898}, mesh = {Breast Neoplasms/*pathology/*virology ; Carcinoma, Medullary/pathology/virology ; Female ; Herpesvirus 4, Human/*isolation & purification ; Humans ; Immunohistochemistry ; *Lymphatic Metastasis ; Retrospective Studies ; }, abstract = {OBJECTIVE: the purpose of our work is to detect Epstein-Barr virus (EBV) in 2 types of breast cancer: medullary carcinoma and high grade invasive ductal carcinoma with lymphoid stroma.

PATIENTS AND METHODS: we proceeded to a retrospective study of 18 medullary carcinoma and 18 high grade invasive ductal carcinoma with lymphoid stroma. The detection of the virus was carried out by immunohistochemistry with anti-LMP2 antibody and by hybridization in situ by oligonucleotides EBER1 and EBER1. LMP1 as well as hybridization in situ were positive in 5 tumors (3 medullary carcinoma and 2 high grade invasive ductal carcinoma with lymphoid stroma).

RESULTS: positivity was observed in tumor cells and neither in epithelial non tumoral ones nor in lymphoid cells.

DISCUSSION AND CONCLUSIONS: during numerous years, correlations between the replication of EBV and the appearance of a malignant phenotype were limited to nasopharyngeal carcinoma and to lymphoid cells. A controversy regarding the association of EBV with breast cancers has recently been reported in the literature. This cancer being very frequent, the involvement of EBV even in a small proportion of breast cancers could have important implications. Our results suggest a possible implication of EBV in these tumours but other studies are necessary.}, } @article {pmid18222386, year = {2008}, author = {Morrogh, M and Morris, EA and Liberman, L and Van Zee, K and Cody, HS and King, TA}, title = {MRI identifies otherwise occult disease in select patients with Paget disease of the nipple.}, journal = {Journal of the American College of Surgeons}, volume = {206}, number = {2}, pages = {316-321}, doi = {10.1016/j.jamcollsurg.2007.07.046}, pmid = {18222386}, issn = {1879-1190}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology/surgery ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Middle Aged ; *Nipples ; Paget's Disease, Mammary/diagnostic imaging/*pathology/surgery ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {INTRODUCTION: For patients with Paget disease (PD) of the nipple, preoperative imaging to detect and evaluate the extent of an underlying malignancy can facilitate appropriate treatment planning. The purpose of this study was to evaluate the role of breast MRI in this setting.

STUDY DESIGN: Using ICD-9 codes for "breast symptoms," we identified 2,294 patients without a current cancer diagnosis seen at our institution (1995 to 2006). Sixty-nine patients (3%) had nipple changes suspicious for PD as the only physical finding. Skin/nipple biopsy confirmed PD in 39 of 69 (57%) patients. Thirty-four patients were eligible for review.

RESULTS: Surgical pathology identified cancer in 32 of 34 (94%) patients (7 invasive ductal carcinoma, 25 ductal carcinoma in situ). Nineteen (59%) cancers were confined to the central quadrant of the breast (unifocal). Preoperative imaging (mammography 34 of 34, MRI 13 of 34) detected 15 of 32 (49%) cancers. Mammography detected 11 cancers, accurately demonstrating extent of disease in 9 of 11 patients. MRI detected seven cancers, accurately demonstrating extent of disease in six of seven patients. After positive mammography (n = 11), MRI (n = 5) did not change management. After negative mammography (n = 23), MRI (n = 8) detected otherwise occult disease in 4 of 8 patients, accurately demonstrating extent of disease in 4 of 4 patients and ruling out an underlying cancer in 1 of 1 patient.

CONCLUSIONS: Ninety-four percent of patients with biopsy-proved PD as the only physical finding had an underlying cancer and 59% had unifocal disease. Negative preoperative imaging did not reliably exclude an underlying cancer, but the increased sensitivity of MRI detected otherwise occult disease. In the setting of negative mammography, MRI can facilitate treatment planning for patients with PD.}, } @article {pmid18219900, year = {2007}, author = {Sakurai, K and Enomoto, K and Kitajima, A and Tani, M and Amano, S}, title = {[A case of advanced breast cancer successfully treated with multi-disciplinary therapy and S-1 administration].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {12}, pages = {2065-2067}, pmid = {18219900}, issn = {0385-0684}, mesh = {Biopsy, Needle ; Breast Neoplasms/*drug therapy/*pathology/radiotherapy ; Drug Combinations ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Oxonic Acid/administration & dosage/*therapeutic use ; Tegafur/administration & dosage/*therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {We report a case of advanced breast cancer (T4b, N3c, M1) achieving a significant improvement on QOL by multi-disciplinary therapy and S-1 administration. The patient was a 59-year-old woman who had ulcerative breast lump with bleeding. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma negative for estrogen receptor, progesterone receptor, and HER2/neu protein expression. The aspiration biopsy cytology was performed from skin lesion, the diagnosis was class V. She received 6 cycles of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2) therapy. The effect of the breast tumor was partial response, and the bleeding from the breast lump was improved. But the response from metastatic skin tumor was less satisfactory. We performed a radiation therapy (20 Gy) to metastatic skin tumor, and the lesion disappeared after the radiation therapy. Then, we tried docetaxel, but the side effect appeared. So, we started administering S-1 after docetaxel. One year later, she was estimated to be in the long stable disease. Multi-disciplinary therapy can improve a patient QOL and the clinical outcomes in Stage IV advanced breast cancer.}, } @article {pmid18219094, year = {2008}, author = {Tsai, WC and Chu, CH and Yu, CP and Sheu, LF and Chen, A and Chiang, H and Jin, JS}, title = {Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters.}, journal = {Disease markers}, volume = {24}, number = {2}, pages = {89-99}, doi = {10.1155/2008/945197}, pmid = {18219094}, issn = {0278-0240}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/mortality/pathology ; Carcinoma, Ductal, Breast/*chemistry/mortality/pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins/*analysis ; Middle Aged ; Neoplasm Proteins/*analysis ; Neoplasm Staging ; Serine Endopeptidases/*analysis ; Survivin ; Tissue Array Analysis/*methods ; }, abstract = {OBJECTIVE: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters.

METHODS: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III).

RESULTS: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages.

CONCLUSIONS: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.}, } @article {pmid18199073, year = {2008}, author = {Luth, JA and Hubbard, GB and Dick, EJ and Frazier, SR and Barrier, BF}, title = {Characterization of spontaneous mammary gland carcinomas in female baboons.}, journal = {Journal of medical primatology}, volume = {37}, number = {1}, pages = {55-61}, doi = {10.1111/j.1600-0684.2007.00273.x}, pmid = {18199073}, issn = {0047-2565}, mesh = {Animals ; Carcinoma, Ductal, Breast/pathology/*veterinary ; Female ; Mammary Neoplasms, Animal/*pathology ; Monkey Diseases/*pathology ; *Papio ; }, abstract = {Spontaneous mammary gland carcinomas occurred in five baboons during a 13-year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co-existent ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.}, } @article {pmid18187183, year = {2008}, author = {Hanley, K and Wang, J and Bourne, P and Yang, Q and Gao, AC and Lyman, G and Tang, P}, title = {Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast.}, journal = {Human pathology}, volume = {39}, number = {3}, pages = {386-392}, doi = {10.1016/j.humpath.2007.07.007}, pmid = {18187183}, issn = {0046-8177}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Transformation, Neoplastic/*metabolism/pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness/pathology ; Receptor, ErbB-2/biosynthesis ; Receptors, Androgen/*biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; }, abstract = {Androgen receptor has been implicated in the pathogenesis of breast carcinoma. In this study, we explored the potential role of androgen receptor in breast cancer by analyzing its expression using immunohistochemistry and its relationship with tumor progress (ductal carcinoma in situ [DCIS] versus invasive ductal carcinoma [IDC]); nuclear grades (high grade [HG] versus non-high grade); expression of estrogen receptor (ER), progesterone receptor (PR), HER-2; and 3 molecular classifications: cytokeratin classification, triple (ER/PR/HER-2) negative classification, and ER/HER-2 classification in 184 breast carcinomas. We found that (1) lack of androgen receptor expression was associated with HG-IDC and with basal subtypes of HG-IDC, suggesting androgen receptor may play an important role in preventing the invasive transformation in this subgroup of breast carcinoma. (2) HG-IDC and HG-DCIS more frequently expressed androgen receptor than ER (55%-93% for androgen receptor and 18%-30% for ER) and were frequently androgen receptor+/ER- (63% for HG-DCIS and 39% for HG-IDC), which made androgen receptor a possible therapeutic target. (3) One third of HG-IDC was negative for androgen receptor, ER, PR, and HER-2, suggesting that further studies are needed to identify other key molecules for targeted therapy. We purpose that androgen receptor should be routinely measured for breast cancer.}, } @article {pmid18186882, year = {2008}, author = {Steinman, S and Bourne, P and Yang, Q and Tang, P and Wang, J}, title = {Some DCIS is different molecularly from DCIS with co-existing IDC.}, journal = {The breast journal}, volume = {14}, number = {1}, pages = {122-123}, doi = {10.1111/j.1524-4741.2007.00536.x}, pmid = {18186882}, issn = {1524-4741}, mesh = {Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism ; Estrogen Receptor alpha/biosynthesis/genetics ; Female ; Gene Expression ; Humans ; Receptor, ErbB-2/biosynthesis/genetics ; Receptors, Progesterone/biosynthesis/genetics ; }, } @article {pmid18181271, year = {2007}, author = {Modolo, J and Garenne, A and Henry, J and Beuter, A}, title = {Development and validation of a neural population model based on the dynamics of a discontinuous membrane potential neuron model.}, journal = {Journal of integrative neuroscience}, volume = {6}, number = {4}, pages = {625-655}, doi = {10.1142/s0219635207001672}, pmid = {18181271}, issn = {0219-6352}, mesh = {Animals ; Computer Simulation ; Membrane Potentials/*physiology ; *Models, Neurological ; Neural Networks, Computer ; Neurons/*physiology ; *Nonlinear Dynamics ; Reproducibility of Results ; Synapses/physiology ; }, abstract = {The major goal of this study was to develop a population density based model derived from statistical mechanics based on the dynamics of a discontinuous membrane potential neuron model. A secondary goal was to validate this model by comparing results from a direct simulation approach on the one hand and our population based approach on the other hand. Comparisons between the two approaches in the case of a synaptically uncoupled and a synaptically coupled neural population produced satisfactory qualitative agreement in terms of firing rate and mean membrane potential. Reasonable quantitative agreement was also obtained for these variables in performed simulations. The results of this work based on the dynamics of a discontinuous membrane potential neuron model provide a basis to simulate phenomenologically large-scale neuronal networks with a reasonably short computing time.}, } @article {pmid20824038, year = {2008}, author = {Reimer, T}, title = {Management of Rare Histological Types of Breast Tumours.}, journal = {Breast care (Basel, Switzerland)}, volume = {3}, number = {3}, pages = {190-196}, pmid = {20824038}, issn = {1661-3791}, abstract = {Breast tumours exhibit a wide range of morphological phenotypes, and specific histopathological types have particular prognostic and clinical characteristics. The management of uncommon premalignant and malignant lesions is often controversial due to the lack of large single-institution studies or randomised trials to define optimal treatments. In the era of frequent use of treatment guidelines, only a low level of evidence exists for the management of rare histological types of breast tumours. This review is divided into two parts: Firstly, the favourable histological subtypes like tubular, mucinous, medullary breast cancers, and phyllodes tumour (benign, borderline, and malignant) are discussed. The prognosis of these selected lesions is believed to be better than for invasive ductal carcinoma so that in some cases even less aggressive treatment should be considered. Patients with these specific histological types should be informed of this relatively favourable prognosis. Secondly, management recommendations for special situations like Paget's disease (tumour of the nipple) and inflammatory breast carcinoma are presented.}, } @article {pmid18165279, year = {2008}, author = {Melnikov, AA and Scholtens, DM and Wiley, EL and Khan, SA and Levenson, VV}, title = {Array-based multiplex analysis of DNA methylation in breast cancer tissues.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {10}, number = {1}, pages = {93-101}, pmid = {18165279}, issn = {1525-1578}, mesh = {Breast Neoplasms/*genetics ; Cell Line, Tumor ; *DNA Methylation ; Female ; Genes, Neoplasm ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis/*methods/*standards ; Reproducibility of Results ; }, abstract = {Abnormal DNA methylation is well established for cancer cells, but a methylation-based diagnostic test is yet to be developed. One of the problems is insufficient accuracy of cancer detection in heterogeneous clinical specimens when only a single gene is analyzed. A new technique was developed to produce a multigene methylation signature in each sample, and its potential for selection of informative genes was tested using DNA from formalin-fixed, paraffin-embedded breast cancer tissues. Fifty-six promoters were analyzed in each of 138 clinical specimens by a microarray-based modification of the previously developed technique. Specific methylation signatures were identified for atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Informative promoters selected by Fisher's exact test were used for composite biomarker design using naïve Bayes algorithm. All informative promoters were unmethylated in disease compared with normal tissue. Cross-validation showed 72.4% sensitivity and 74.7% specificity for detection of ductal carcinoma in situ and invasive ductal carcinoma, and 87.5% sensitivity and 95% specificity for detection of atypical ductal hyperplasia. These results indicate that informative cancer-specific methylation signatures can be detected in heterogeneous tissue specimens, suggesting that a diagnostic assay can then be developed.}, } @article {pmid18164408, year = {2008}, author = {Lamovec, J and Falconieri, G and Salviato, T and Pizzolitto, S}, title = {Basaloid carcinoma of the breast: a review of 9 cases, with delineation of a possible clinicopathologic entity.}, journal = {Annals of diagnostic pathology}, volume = {12}, number = {1}, pages = {4-11}, doi = {10.1016/j.anndiagpath.2007.01.009}, pmid = {18164408}, issn = {1092-9134}, mesh = {Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/surgery ; Carcinoma, Transitional Cell/metabolism/*pathology/surgery ; Fatal Outcome ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, abstract = {Basaloid carcinoma of the breast (BCB) is an unusual neoplasm composed of basal-type neoplastic cells similar to those found in adenoid cystic carcinoma (ACC), although lacking distinctive features such as a cribriform pattern, a dual neoplastic population (epithelial-myoepithelial/basaloid), and stromal deposits of basement membrane-like material. In this article, we present 9 cases of breast cancer showing overall/predominant basaloid morphology. Patients' ages ranged from 47 to 75 years (mean, 61.4 years). Surgical treatment included mastectomy or quadrant excision with or without axillary dissection. Most tumors had a circumscribed outline and ranged in size from 1.3 to 5.5 cm (mean, 2.5 cm). Microscopically, they featured sheets, nests, and cords of proliferating basaloid tumor cells with ovoid, hyperchromatic nuclei with inconspicuous nucleoli and scant cytoplasm. No foci with characteristics of ACC were found in any of the tumors. Transition into pleomorphic basaloid carcinoma with foci of high-grade ductal carcinoma in situ plus infiltrating ductal carcinoma (IDC) and admixture with grade 3 ductal and sarcomatoid carcinoma was seen in 2 cases. Tumor cells were positive for wide-spectrum keratins and epithelial membrane antigen (9/9) and high-molecular-weight keratins (7/9). They were negative for smooth muscle actin, p63, calponin, and CD10 in all tested cases. Estrogen receptor, progesterone receptor, and HER-2 were negative. Axillary lymph node metastases were seen in 3 cases. At follow-up (range, 10-169 months), 5 patients were alive, 1 with evidence of contralateral breast cancer. Three patients died: one of disseminated BCB metastases, another of liver cirrhosis, and one of disseminated estrogen receptor/progesterone receptor-positive contralateral IDC. One patient was lost to follow-up. We concluded that BCB has some phenotypic and immunohistochemical features enabling its distinction from ACC or IDC. It appears to be a morphological and possibly a clinical entity. Compared with ACC, BCB appears to be more aggressive and may entail a more guarded prognosis.}, } @article {pmid18154662, year = {2007}, author = {O'Rourke, JA and Charlson, DV and Gonzalez, DO and Vodkin, LO and Graham, MA and Cianzio, SR and Grusak, MA and Shoemaker, RC}, title = {Microarray analysis of iron deficiency chlorosis in near-isogenic soybean lines.}, journal = {BMC genomics}, volume = {8}, number = {}, pages = {476}, pmid = {18154662}, issn = {1471-2164}, mesh = {Cluster Analysis ; DNA, Complementary/genetics ; Expressed Sequence Tags ; FMN Reductase/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant/*genetics ; Genes, Plant/genetics ; Hydroponics ; Iron/*metabolism ; *Iron Deficiencies ; Multigene Family/genetics ; *Oligonucleotide Array Sequence Analysis ; Phenotype ; Plant Diseases/*genetics ; Plant Roots/genetics/metabolism ; Polymerase Chain Reaction ; RNA, Plant/analysis/genetics ; Soybeans/enzymology/*genetics/*metabolism ; }, abstract = {BACKGROUND: Iron is one of fourteen mineral elements required for proper plant growth and development of soybean (Glycine max L. Merr.). Soybeans grown on calcareous soils, which are prevalent in the upper Midwest of the United States, often exhibit symptoms indicative of iron deficiency chlorosis (IDC). Yield loss has a positive linear correlation with increasing severity of chlorotic symptoms. As soybean is an important agronomic crop, it is essential to understand the genetics and physiology of traits affecting plant yield. Soybean cultivars vary greatly in their ability to respond successfully to iron deficiency stress. Microarray analyses permit the identification of genes and physiological processes involved in soybean's response to iron stress.

RESULTS: RNA isolated from the roots of two near isogenic lines, which differ in iron efficiency, PI 548533 (Clark; iron efficient) and PI 547430 (IsoClark; iron inefficient), were compared on a spotted microarray slide containing 9,728 cDNAs from root specific EST libraries. A comparison of RNA transcripts isolated from plants grown under iron limiting hydroponic conditions for two weeks revealed 43 genes as differentially expressed. A single linkage clustering analysis of these 43 genes showed 57% of them possessed high sequence similarity to known stress induced genes. A control experiment comparing plants grown under adequate iron hydroponic conditions showed no differences in gene expression between the two near isogenic lines. Expression levels of a subset of the differentially expressed genes were also compared by real time reverse transcriptase PCR (RT-PCR). The RT-PCR experiments confirmed differential expression between the iron efficient and iron inefficient plants for 9 of 10 randomly chosen genes examined. To gain further insight into the iron physiological status of the plants, the root iron reductase activity was measured in both iron efficient and inefficient genotypes for plants grown under iron sufficient and iron limited conditions. Iron inefficient plants failed to respond to decreased iron availability with increased activity of Fe reductase.

CONCLUSION: These experiments have identified genes involved in the soybean iron deficiency chlorosis response under iron deficient conditions. Single linkage cluster analysis suggests iron limited soybeans mount a general stress response as well as a specialized iron deficiency stress response. Root membrane bound reductase capacity is often correlated with iron efficiency. Under iron-limited conditions, the iron efficient plant had high root bound membrane reductase capacity while the iron inefficient plants reductase levels remained low, further limiting iron uptake through the root. Many of the genes up-regulated in the iron inefficient NIL are involved in known stress induced pathways. The most striking response of the iron inefficient genotype to iron deficiency stress was the induction of a profusion of signaling and regulatory genes, presumably in an attempt to establish and maintain cellular homeostasis. Genes were up-regulated that point toward an increased transport of molecules through membranes. Genes associated with reactive oxidative species and an ROS-defensive enzyme were also induced. The up-regulation of genes involved in DNA repair and RNA stability reflect the inhospitable cellular environment resulting from iron deficiency stress. Other genes were induced that are involved in protein and lipid catabolism; perhaps as an effort to maintain carbon flow and scavenge energy. The under-expression of a key glycolitic gene may result in the iron-inefficient genotype being energetically challenged to maintain a stable cellular environment. These experiments have identified candidate genes and processes for further experimentation to increase our understanding of soybeans' response to iron deficiency stress.}, } @article {pmid18154115, year = {2007}, author = {Kriuchkov, AN}, title = {[Extent of destructive changes in tumor parenchyma of breast cancer patients of various age].}, journal = {Voprosy onkologii}, volume = {53}, number = {5}, pages = {531-534}, pmid = {18154115}, issn = {0507-3758}, mesh = {Adult ; Age Factors ; Aged ; Apoptosis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Female ; Humans ; Middle Aged ; Necrosis ; }, abstract = {Extent of viable tumor parenchyma and necrotic tissue as well as grade of tumor cell apoptosis were assessed using histological samples from 377 patients with invasive ductal carcinoma of the breast. No preoperative chemo- or radiotherapy was given. Patients of varying age were examined for destructive changes in tumor nodes both in absence and presence of regional metastases. The highest viability was registered in patients aged 30-39 years. There was a reverse correlation between age, on the one hand, and extent of intact tumor parenchyma, on the other. Similarly, the same age group revealed relatively pronounced destructive changes such as necrosis and apoptosis which are generally characteristic of younger age. There was a significant relationship between extent of destructive changes and malignant anaplasia.}, } @article {pmid18089497, year = {2008}, author = {Hara, H and Suda, K}, title = {Review of the cytologic features of noninvasive ductal carcinomas of the pancreas: differences from invasive ductal carcinoma.}, journal = {American journal of clinical pathology}, volume = {129}, number = {1}, pages = {115-129}, doi = {10.1309/PHV2244LC8B0P7TR}, pmid = {18089497}, issn = {0002-9173}, mesh = {Adenocarcinoma, Mucinous/metabolism/pathology ; Adenocarcinoma, Papillary/metabolism/pathology ; Adenoma/pathology ; Biomarkers, Tumor/metabolism ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Cell Nucleus/pathology ; Diagnosis, Differential ; Humans ; Hyperplasia/pathology ; Mucins/metabolism ; Neoplasm Invasiveness/pathology ; Pancreatic Neoplasms/metabolism/*pathology ; }, abstract = {Invasive ductal adenocarcinoma (IDA) of the pancreas (IDAP) originating from the ductal gland has a poor prognosis. Noninvasive carcinomas are principally intraductal papillary mucinous carcinomas (IPMCs) and pancreatic intraepithelial neoplasms 3 (PanIN-3). Small papillary-cohesive clusters, individually well-enveloped nuclei in well-preserved cytoplasm, centrally located nuclei, small nuclei (about 10 mum), euchromatin, clearly defined cell borders, small cytoplasm without prominent anisocytosis and no cytoplasm more than 21 mum in shortest diameter, a mixture of goblet cells, and a pleomorphic aspect are common in IPMC and intraductal papillary mucinous neoplasm (IPMN), whereas malignancy in nuclei are observed only in IPMC. PanIN-3 cells have small papillary-cohesive and compact clusters, a monomorphic aspect, and small dense cytoplasm and are highly suggestive of malignancy. IDA cells have loose sheet and solid clusters, poorly preserved cytoplasm, nuclei that tend to adhere to each other, large nuclei, a combination of large nuclei (short diameter <15 mum) with hyperchromatin, a monomorphic aspect, and abundant cytoplasm more than 21 mum in the shortest diameter. To preoperatively differentiate noninvasive IPMC and PanIN-3 from IDAP, these features would be clinically very useful.}, } @article {pmid18087220, year = {2007}, author = {Signorino, E and Brusa, D and Granata, R and Malavasi, F and Ferrone, S and Matera, L}, title = {Contribution of dendritic cells' FcgammaRI and FcgammaRIII to cross-presentation of tumor cells opsonized with the anti-MHC class I monoclonal antibodies.}, journal = {Cancer biology & therapy}, volume = {6}, number = {12}, pages = {1932-1937}, doi = {10.4161/cbt.6.12.4973}, pmid = {18087220}, issn = {1555-8576}, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; Antibody Specificity ; Antigen Presentation/*immunology ; Antigens, Neoplasm/*immunology/metabolism ; Carcinoma/immunology/pathology ; Cell Differentiation/immunology ; Cell Line, Tumor/immunology ; Coculture Techniques ; Cytokines/pharmacology ; Dendritic Cells/drug effects/*immunology ; GPI-Linked Proteins ; HLA-A2 Antigen/*immunology/metabolism ; Humans ; Interferon-gamma/biosynthesis ; K562 Cells/immunology ; Mice ; Opsonin Proteins/*immunology ; Receptors, IgG/*immunology ; Stomach Neoplasms/immunology/pathology ; T-Lymphocytes, Cytotoxic/immunology ; }, abstract = {Dendritic cells (DC) operate through an immature (iDC) step (where tumor antigens are internalized) and a mature step (mDC) (where tumor antigens (TA) are cross-presented to naive TA-specific cytotoxic T lymphocyte (CTL) progenitors). Receptors by which cellbound antigens can access the DC cross-presentation pathway include the Fcgamma receptors (FcgammaR). This route has been exploited to deliver opsonized tumors to DC and promising results have been obtained with mAbs raised against overexpressed or specific tumor antigens. In order to extend this strategy to tumor for which no antigens have been described, we have exploited the ubiquitous molecule MHC Class I as target antigen. The low membrane expression of tumor antigens on KATO cells, a previously studied human gastric carcinoma cell line, suggested its use here as a model. The IgG1 TP25.99 and the IgG2a W6/32 anti-MHC Class I mAbs, which strongly reacted with KATO cells, where employed as tumor coating mAbs. Since these mAbs recognize the FcgammaRI (CD64) and FcgammaRIII (CD16), respectively on DCs, the frequencies of the two classes of FcgammaRI on DCs was evaluated. CD64 was expressed on 35% of iDCs compared to 11% expression of CD16, the two molecules being co-expressed. IgG1 mAb-opsonized KATO (KATO(TP25)) cells were taken up by iDCs with the same efficiency as KATO cells opsonized with IgG2a mAb (KATO(W6/32)), but induced a higher expression of the maturation marker CD83. CTL cross-priming by KATO(TP25) (but not KATO(W6/32))-loaded and cytokine-matured DCs was also higher than cross-priming induced by uncoated- or FcgammaRI-targeted KATO(W6/32)-DC. Together the present results indicate that: (i) MHC Class I antigens are advantageous antigens for targeting tumor cells to the FcgammaR-mediated cross-presentation pathway and (ii) immunogenic signals seem to be prevalently conveyed by FcgammaRIII.}, } @article {pmid18086787, year = {2007}, author = {Li, CI and Daling, JR}, title = {Changes in breast cancer incidence rates in the United States by histologic subtype and race/ethnicity, 1995 to 2004.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {16}, number = {12}, pages = {2773-2780}, doi = {10.1158/1055-9965.EPI-07-0546}, pmid = {18086787}, issn = {1055-9965}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Ethnicity ; Female ; Humans ; Incidence ; Middle Aged ; Racial Groups ; SEER Program ; United States ; }, abstract = {Breast cancer incidence rates rose throughout the 1980s and 1990s in the United States but have recently declined through 2004. Studies reporting this decline primarily attribute it to the sharp decline in menopausal hormone use following publication of the Women's Health Initiative trial results. However, they have not stratified rates by either histologic type or race/ethnicity, which could further inform contributors to these trends. Using data from 13 cancer registries that participate in the Surveillance, Epidemiology, and End Results program, we evaluated annual percent changes (APC) in breast cancer incidence rates from 1995 to 2004 by histologic type and race/ethnicity for intervals identified using joinpoint regression. Invasive ductal carcinoma and invasive lobular carcinoma incidence rates fell steadily from 1998 to 2004 [APC, -3.07% (95% confidence interval, -4.10 to -2.02) and APC, -3.18% (95% confidence interval, -5.18 to -1.03), respectively]. Declines in rates of breast cancer overall and invasive ductal carcinoma were primarily limited to women > or = 50 years of age and to non-Hispanic whites and Asian/Pacific Islanders, and declines in rates of invasive lobular carcinoma were primarily limited to non-Hispanic whites. The majority of these declines began around 1998 and all began before 2002 when the Women's Health Initiative trial results were published; thus, the abrupt decline in hormone therapy use starting in 2002 is unlikely to be primarily responsible for the recent decline in breast cancer rates. The declines observed thus far are likely attributable to saturation of screening, although further declines related to the widespread cessation of hormone use may follow.}, } @article {pmid18084246, year = {2008}, author = {Ferreira, M and Albarracin, CT and Resetkova, E}, title = {Pseudoangiomatous stromal hyperplasia tumor: a clinical, radiologic and pathologic study of 26 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {21}, number = {2}, pages = {201-207}, doi = {10.1038/modpathol.3801003}, pmid = {18084246}, issn = {0893-3952}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast/*pathology/surgery ; Breast Diseases/diagnostic imaging/*pathology/surgery ; Breast Neoplasms/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; Hyperplasia/pathology ; Mammography ; Middle Aged ; Premenopause ; Retrospective Studies ; Stromal Cells/pathology ; Ultrasonography, Mammary ; }, abstract = {Pseudoangiomatous stromal hyperplasia tumors are rare. In this retrospective study, we evaluated the clinical, radiologic, and pathologic features of pseudoangiomatous stromal hyperplasia tumors and compared histologic findings of pseudoangiomatous stromal hyperplasia tumors with clinical outcome. We identified 26 patients (mean age, 47 years) with pseudoangiomatous stromal hyperplasia tumors who had been diagnosed at our institution. Sixteen patients (62%) were premenopausal, and 13 (50%) had a history of oral contraceptive or hormone replacement therapy use. Ten patients (38%) presented with a palpable mass; in the other patients, the tumors were detected by mammography (where it usually appeared as a hyperdense mass with irregular margins) or sonography (where it usually appeared as a hypoechoic mass). Lesions were a mean of 4.2 cm at the largest dimension (range, 0.8-11 cm). Histologically, pseudoangiomatous stromal hyperplasia was classified as simple in 18 patients (69%) and fascicular/proliferative in eight patients (31%). In one patient (4%), an invasive ductal carcinoma was present within the pseudoangiomatous stromal hyperplasia tumor. We found associated benign epithelial lesions in eight patients (31%) and/or gynecomastia-like changes in 17 patients (65%). The presence of gynecomastia-like changes was significantly associated with intralobular location of pseudoangiomatous stromal hyperplasia (P=0.00085, by Fisher's exact test). Follow-up data were available for 15 patients (mean +/- s.d., < or =27 +/- 17 months). No additional pathology or substantial changes in existing lesions were found on imaging. All pseudoangiomatous stromal hyperplasia tumors diagnosed by core needle biopsy but not subsequently excised remained clinically and radiologically stable; therefore, offering the option of close clinical surveillance instead of surgery in patients with pseudoangiomatous stromal hyperplasia tumors diagnosed by core needle biopsy in selected patients.}, } @article {pmid18067637, year = {2008}, author = {Yamaguchi, R and Furusawa, H and Nakahara, H and Inomata, M and Namba, K and Tanaka, M and Ohkuma, K and Tayama, K and Fujii, T and Yano, H and Kage, M and Kojiro, M}, title = {Clinicopathological study of invasive ductal carcinoma with large central acellular zone: special reference to magnetic resonance imaging findings.}, journal = {Pathology international}, volume = {58}, number = {1}, pages = {26-30}, doi = {10.1111/j.1440-1827.2007.02184.x}, pmid = {18067637}, issn = {1320-5463}, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Contrast Media ; Female ; Humans ; Image Enhancement ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; *Magnetic Resonance Imaging ; Middle Aged ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Invasive ductal carcinoma (IDC) with central acellular zone is sometimes encountered, but its clinicopathological features have not yet been fully investigated. The clinicopathological features of 10 resected cases of IDC with a large central acellular zone were investigated. The tumor size ranged from 6 to 28 mm with a mean of 14.3 +/- 6.9 mm. Contrast-enhanced magnetic resonance imaging (MRI) showed a ring-like appearance in the tumor. Sagittal fat-suppressed T2-weighted MRI had very high to intermediate signal intensity in a central area. Histologically, cancer tissue was located in the periphery of the tumor with a ring-like pattern and a large central area was occupied by acellular amorphous tissue that was strongly stained by alcian blue. Lymph vessel permeation was seen in eight cases. Among the tumors with focal enhancement in the central areas >1 cm in diameter on contrast MRI, marked increase of microvessel was observed in the enhanced spot. The mean of p53 and Ki-67 labeling indices was 56.2% and 36.3%, respectively. IDC with a large central acellular zone presenting with characteristic MRI should be noted as a new morphological entity.}, } @article {pmid18059219, year = {2007}, author = {Mitsunaga, S and Hasebe, T and Kinoshita, T and Konishi, M and Takahashi, S and Gotohda, N and Nakagohri, T and Ochiai, A}, title = {Detail histologic analysis of nerve plexus invasion in invasive ductal carcinoma of the pancreas and its prognostic impact.}, journal = {The American journal of surgical pathology}, volume = {31}, number = {11}, pages = {1636-1644}, doi = {10.1097/PAS.0b013e318065bfe6}, pmid = {18059219}, issn = {0147-5185}, mesh = {Aged ; Autonomic Pathways/*pathology ; Carcinoma, Pancreatic Ductal/mortality/*pathology/surgery ; Cell Differentiation ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Necrosis ; Neoplasm Invasiveness ; Nerve Fibers/*pathology ; Pancreas/*innervation/pathology/surgery ; Pancreatic Neoplasms/mortality/*pathology/surgery ; Pancreaticoduodenectomy ; Prognosis ; Proportional Hazards Models ; Time Factors ; }, abstract = {Nerve plexus invasion is regarded as one of the most important prognostic factors in invasive ductal carcinoma (IDC) of the pancreas, though nerve plexus invasion has not been evaluated in terms of prognostic impact on the basis of detailed histologic investigation. The purpose of this study was to precisely examine morphologic characteristics of nerve plexus invasion and analyze its prognostic predictive power compared with the well-known prognostic parameters of pancreatic IDCs. The outcome and histologic features of 75 patients with pancreatic IDC in the pancreas head were investigated, and 422 lesions of nerve plexus invasion were evaluated. Tumor cells invading nerve plexus showed a duct-forming differentiated feature and predominantly existed in the perineurium and perineural space. Multivariate analyses revealed that the important prognostic factors, in addition to invasive tumor size and tumor necrosis, were at long distances from nerve plexus invasion to pancreatic capsule and perineural invasion in nerve plexus invasion.}, } @article {pmid18056365, year = {2007}, author = {Bax, M and García-Vallejo, JJ and Jang-Lee, J and North, SJ and Gilmartin, TJ and Hernández, G and Crocker, PR and Leffler, H and Head, SR and Haslam, SM and Dell, A and van Kooyk, Y}, title = {Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {179}, number = {12}, pages = {8216-8224}, doi = {10.4049/jimmunol.179.12.8216}, pmid = {18056365}, issn = {0022-1767}, support = {081882/WT_/Wellcome Trust/United Kingdom ; GM62116/GM/NIGMS NIH HHS/United States ; }, mesh = {Dendritic Cells/*immunology ; Galectins/*immunology ; Gene Expression Profiling ; Glycosylation ; Glycosyltransferases/genetics ; Humans ; Lectins/*immunology ; Oligonucleotide Array Sequence Analysis ; Polysaccharides/*biosynthesis/genetics ; Sialic Acid Binding Immunoglobulin-like Lectins ; }, abstract = {Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic cells (iDC) reside in the tissue where they capture pathogens whereas mature dendritic cells (mDC) are able to activate T cells in the lymph node. This dramatic functional change is mediated by an important genetic reprogramming. Glycosylation is the most common form of posttranslational modification of proteins and has been implicated in multiple aspects of the immune response. To investigate the involvement of glycosylation in the changes that occur during DC maturation, we have studied the differences in the glycan profile of iDC and mDC as well as their glycosylation machinery. For information relating to glycan biosynthesis, gene expression profiles of human monocyte-derived iDC and mDC were compared using a gene microarray and quantitative real-time PCR. This gene expression profiling showed a profound maturation-induced up-regulation of the glycosyltransferases involved in the expression of LacNAc, core 1 and sialylated structures and a down-regulation of genes involved in the synthesis of core 2 O-glycans. Glycosylation changes during DC maturation were corroborated by mass spectrometric analysis of N- and O-glycans and by flow cytometry using plant lectins and glycan-specific Abs. Interestingly, the binding of the LacNAc-specific lectins galectin-3 and -8 increased during maturation and up-regulation of sialic acid expression by mDC correlated with an increased binding of siglec-1, -2, and -7.}, } @article {pmid18051157, year = {2007}, author = {Kim, KB and Park, CS}, title = {Application of RF varactor using Ba(x)Sr(1-x)TiO3/TiO2/HR-Si substrate for reconfigurable radio.}, journal = {IEEE transactions on ultrasonics, ferroelectrics, and frequency control}, volume = {54}, number = {11}, pages = {2227-2232}, doi = {10.1109/tuffc.2007.527}, pmid = {18051157}, issn = {0885-3010}, abstract = {In this paper, the potential feasibility of integrating Ba(x)Sr(1-x)TiO3 (BST) films into Si wafer by adopting tunable interdigital capacitor (IDC) with TiO2 thin film buffer layer and a RF tunable active bandpass filter (BPF) using BST based capacitor are proposed. TiO2 as a buffer layer is grown onto Si substrate by atomic layer deposition (ALD) and the interdigital capacitor on BST(500 nm)/TiO2 (50 nm)/HR-Si is fabricated. BST interdigital tunable capacitor integrated on HR-Si substrate with high tunability and low loss tangent are characterized for their microwave performances. BST/TiO2/HR-Si IDC shows much enhanced tunability values of 40% and commutation quality factor (CQF) of 56.71. A resonator consists of an active capacitance circuit together with a BST varactor. The active capacitor is made of a field effect transistor (FET) that exhibits negative resistance as well as capacitance. The measured second order active BPF shows bandwidth of 110 MHz, insertion loss of about 1 dB at the 1.81 GHz center frequency and tuning frequency of 230 MHz (1.81-2.04 GHz).}, } @article {pmid18045769, year = {2008}, author = {Kijima, Y and Yoshinaka, H and Koriyama, C and Funasako, Y and Natsugoe, S and Aikou, T}, title = {Ultrasound examination is useful for prediction of histologic type in invasive ductal carcinoma of the breast.}, journal = {Ultrasound in medicine & biology}, volume = {34}, number = {4}, pages = {517-524}, doi = {10.1016/j.ultrasmedbio.2007.09.017}, pmid = {18045769}, issn = {0301-5629}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Risk Factors ; Ultrasonography, Mammary/methods ; }, abstract = {The aim of this study was to estimate the histologic type of invasive ductal carcinoma of the breast according to the ultrasound (US) criteria and to identify the high-risk patients for lymph node metastases. An acceptable preoperative diagnosis of lymph node metastasis is essential when performing the reduction of lymphadenectomy. The positive relationship between histology and prognosis has been reported in breast cancer. However, few reports have examined the relationship between preoperative US findings and histology. Ultrasound examination was performed in 252 patients with invasive ductal carcinoma (91 papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for nodal metastasis were analyzed in clinicopathological findings. After nine criteria were defined based on US findings, all tumors were classified into US histologic type. According to the multivariate analysis, lymph node metastases was significantly associated with tumor size (p < 0.001), histology (p < 0.001) and age (p = 0.038). Histology was an important risk factor for nodal metastasis, especially in scirrhous carcinoma. When comparing the US classification and histology, the accuracy rate of US for papillotubular, solid-tubular and scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of depth-to-width, boundary echo and attenuation of the back echo was important. It is important to preoperatively estimate the histologic type by tumor property using US. Our US classifications may be useful to pick up high-risk patients for nodal metastasis in invasive breast cancer.}, } @article {pmid18042354, year = {2007}, author = {Modolo, J and Mosekilde, E and Beuter, A}, title = {New insights offered by a computational model of deep brain stimulation.}, journal = {Journal of physiology, Paris}, volume = {101}, number = {1-3}, pages = {56-63}, doi = {10.1016/j.jphysparis.2007.10.007}, pmid = {18042354}, issn = {0928-4257}, mesh = {Action Potentials/physiology ; Computational Biology ; *Computer Simulation ; *Deep Brain Stimulation ; Humans ; *Models, Neurological ; Neurons/physiology ; Parkinson Disease/physiopathology/therapy ; }, abstract = {Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully elucidated. The paper starts with a brief review on the use of DBS to treat PD symptoms. The second section introduces a computational model based on the population density approach and the Izhikevich neuron model. We explain why this model is appropriate for investigating macroscopic network effects and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied.}, } @article {pmid18041310, year = {2007}, author = {Al-Joudi, FS and Iskandar, ZA and Imran, AK}, title = {Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast.}, journal = {The Southeast Asian journal of tropical medicine and public health}, volume = {38}, number = {5}, pages = {904-910}, pmid = {18041310}, issn = {0125-1562}, mesh = {Adult ; Apoptosis/physiology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins/*biosynthesis/genetics ; Middle Aged ; Neoplasm Proteins/*biosynthesis/genetics ; Survivin ; Tumor Suppressor Protein p53/*biosynthesis/genetics ; }, abstract = {This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.}, } @article {pmid18035533, year = {2008}, author = {Rakha, EA and El-Sayed, ME and Powe, DG and Green, AR and Habashy, H and Grainge, MJ and Robertson, JF and Blamey, R and Gee, J and Nicholson, RI and Lee, AH and Ellis, IO}, title = {Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {44}, number = {1}, pages = {73-83}, doi = {10.1016/j.ejca.2007.10.009}, pmid = {18035533}, issn = {0959-8049}, mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/drug therapy/mortality/*pathology ; Carcinoma, Ductal, Breast/drug therapy/mortality/*pathology ; Carcinoma, Lobular/drug therapy/mortality/*pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Metastasis/drug therapy/pathology ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Treatment Outcome ; }, abstract = {UNLABELLED: Invasive lobular carcinoma (ILC) comprises approximately 5-15% of breast cancers and appears to have a distinct biology. It is less common than invasive ductal carcinoma (IDC) and few large studies have addressed its biologic characteristics and behaviour with respect to long-term clinical outcome and response to adjuvant therapy.

METHODS: This study is based on a large and well-characterised consecutive series of invasive breast carcinomas with a long-term follow-up (up to 25 years). This series included 415 (8%) patients with pure ILC and 2901 (55.7%) with IDC (not otherwise specified) identified from a consecutive cohort of 5680 breast tumours presented to our Breast Unit that were treated in a similar conventional manner. Clinicopathological, therapy and outcome information as well as data on a large panel of biomarkers were available.

RESULTS: Compared to IDC, patients with ILC tended to be older and present with tumours which are more frequently lower grade (typically, grade 2 [84%]), hormone-receptor positive (86% compared to 61% in IDC), of larger size, and with the absence of vascular invasion. A higher frequency of ILC was placed in the good Nottingham Prognostic Index group (40% compared to 21% in IDC). ILC showed indolent but progressive behavioural characteristics with nearly linear survival curves which crossed those of IDC after approximately 10years of follow-up, thus eventually exhibiting a worse long-term outcome. Importantly, ILC showed a better response to adjuvant hormonal therapy (HT) with improvement in survival in patients who received HT compared with matched patients with IDC.

CONCLUSION: ILC is a distinct entity of breast cancer that responds well to adjuvant HT. These data add important clinical information for assessing the long-term benefits of adjuvant HT use in ILC.}, } @article {pmid18033729, year = {2008}, author = {Doron, G and Moulding, R and Kyrios, M and Nedeljkovic, M}, title = {Sensitivity of self-beliefs in obsessive compulsive disorder.}, journal = {Depression and anxiety}, volume = {25}, number = {10}, pages = {874-884}, doi = {10.1002/da.20369}, pmid = {18033729}, issn = {1520-6394}, mesh = {Adult ; Anxiety Disorders/diagnosis/psychology ; *Culture ; Depression/diagnosis/psychology ; Female ; Humans ; Internal-External Control ; Job Satisfaction ; Male ; Middle Aged ; Morals ; Obsessive-Compulsive Disorder/diagnosis/*psychology ; Reference Values ; *Self Concept ; Social Adjustment ; Social Responsibility ; Young Adult ; }, abstract = {Aspects of self-concept have been implicated in recent cognitive theories of obsessive compulsive disorder (OCD). It has been proposed that OCD is associated with perceptions of incompetence in self-domains considered important by the individual. A previous study in nonclinical individuals found that such "sensitivity of self" in the areas of job competence, morality and social acceptability was associated with elevated OCD symptoms and related beliefs. This study examined whether self-sensitivity is related to higher OCD symptoms and cognitions in individuals with OCD, and whether such self-sensitivity is specific to OCD versus other anxiety disorders. Clinical samples with OCD (N=30), other anxiety disorders (N=20) and a community control sample (N=32) participated in the study. It was found that in the OCD group, sensitivity in moral domains, but not job competence or social acceptability, was associated with higher levels of OCD symptoms and OCD-related beliefs. Sensitivity in the domains of morality and job competence was found in the OCD cohort, whereas individuals with other anxiety disorders did not show such sensitivity, suggesting some specificity of relationships to OCD. Implications for theory and therapy are discussed.}, } @article {pmid18030959, year = {2007}, author = {Katz-Navon, T and Naveh, E and Stern, Z}, title = {Safety self-efficacy and safety performance: potential antecedents and the moderation effect of standardization.}, journal = {International journal of health care quality assurance}, volume = {20}, number = {7}, pages = {572-584}, doi = {10.1108/09526860710822716}, pmid = {18030959}, issn = {0952-6862}, mesh = {*Attitude of Health Personnel ; Health Care Surveys ; Hospitals, General/*organization & administration/standards ; Humans ; Israel ; Medical Errors/prevention & control ; Models, Organizational ; Motivation ; Nursing Staff, Hospital/*psychology ; Safety Management/*organization & administration/standards ; *Self Efficacy ; Surveys and Questionnaires ; }, abstract = {PURPOSE: The purpose of this paper is to suggest a new safety self-efficacy construct and to explore its antecedents and interaction with standardization to influence in-patient safety.

DESIGN/METHODOLOGY/APPROACH: The paper used a survey of 161 nurses using a self-administered questionnaire over a 14-day period in two large Israeli general hospitals. Nurses answered questions relating to four safety self-efficacy antecedents: enactive mastery experiences; managers as safety role models; verbal persuasion; and safety priority, that relate to the perceived level of standardization and safety self-efficacy. Confirmatory factor analysis was used to assess the scale's construct validity. Regression models were used to test hypotheses regarding the antecedents and influence of safety self-efficacy.

FINDINGS: Results indicate that: managers as safety role models; distributing safety information; and priority given to safety, contributed to safety self-efficacy. Additionally, standardization moderated the effects of safety self-efficacy and patient safety such that safety self-efficacy was positively associated with patient safety when standardization was low rather than high. Hospital managers should be aware of individual motivations as safety self-efficacy when evaluating the potential influence of standardization on patient safety.

ORIGINALITY/VALUE: Theoretically, the study introduces a new safety self-efficacy concept, and captures its antecedents and influence on safety performance. Also, the study suggests safety self-efficacy as a boundary condition for the influence of standardization on safety performance. Implementing standardization in healthcare is problematic because not all processes can be standardized. In this case, self-efficacy plays an important role in securing patient safety. Hence, safety self-efficacy may serve as a "substitute-for-standardization," by promoting staff behaviors that affect patient safety.}, } @article {pmid18029860, year = {2007}, author = {Yang, WT and Hennessy, B and Broglio, K and Mills, C and Sneige, N and Davis, WG and Valero, V and Hunt, KK and Gilcrease, MZ}, title = {Imaging differences in metaplastic and invasive ductal carcinomas of the breast.}, journal = {AJR. American journal of roentgenology}, volume = {189}, number = {6}, pages = {1288-1293}, doi = {10.2214/AJR.07.2056}, pmid = {18029860}, issn = {1546-3141}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Mammography/*methods ; Metaplasia/diagnostic imaging ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography, Mammary/methods ; }, abstract = {OBJECTIVE: The purpose of this study was to compare the imaging features of metaplastic breast carcinoma with those of invasive ductal carcinoma.

MATERIALS AND METHODS: Women diagnosed on preoperative mammography or sonography with metaplastic breast carcinoma and T-stage matched invasive ductal carcinoma of the breast from a single pathology database were included in the study. Clinical and pathologic information on all metaplastic cancers was documented. Mammography and sonography variables were recorded using the BI-RADS lexicon. Groups were compared using Fisher's exact test, the chi-square test, or Wilcoxon's rank sum test, as appropriate.

RESULTS: Forty-three patients diagnosed with metaplastic carcinoma were matched to 43 patients with ductal carcinoma by tumor T stage. Patients with metaplastic carcinoma were younger (median, 46 vs 53 years, p = 0.048) than those with ductal carcinoma. Mammographically, metaplastic carcinomas were less frequently irregular in shape (16% vs 74%, p < 0.0001) and less frequently showed microlobulated or spiculated margins (19% vs 56%, p = 0.0008) and calcifications (25% vs 51%, p = 0.02) when compared with ductal carcinomas. Sonographically, metaplastic carcinomas were less frequently irregular in shape (27% vs 69%, p = 0.001) and less frequently showed angular margins (9% vs 49%) and posterior acoustic shadowing (9% vs 49%, p < 0.0001).

CONCLUSION: Characteristic malignant imaging features, including irregular shape, spiculated margins, segmentally distributed pleomorphic calcifications, and posterior acoustic shadowing, are uncommon in metaplastic carcinomas. These carcinomas tend to show more benign imaging features, such as round or oval shape with circumscribed margins, when compared with ductal carcinomas.}, } @article {pmid18028418, year = {2008}, author = {Aessopos, A and Tsironi, M and Polonifi, K and Baltopoulos, P and Vaiopoulos, G}, title = {Intervertebral disc calcification in thalassemia intermedia.}, journal = {European journal of haematology}, volume = {80}, number = {2}, pages = {164-167}, doi = {10.1111/j.1600-0609.2007.00987.x}, pmid = {18028418}, issn = {1600-0609}, mesh = {Adult ; Calcinosis/*complications/etiology ; Female ; Hemochromatosis/complications/etiology ; Humans ; Intervertebral Disc/*physiopathology ; Intervertebral Disc Displacement/*complications/etiology ; Lumbar Vertebrae/diagnostic imaging ; Male ; Middle Aged ; Prevalence ; Radiography, Thoracic ; Treatment Outcome ; X-Rays ; beta-Thalassemia/*complications ; }, abstract = {OBJECTIVES: Intervertebral disc calcification, an age-related phenomenon of variable clinical significance is described in hemochromatosis. As beta-thalassemia is characterized by excessive tissue iron deposition and secondary hemosiderosis, and skeletal abnormalities are often observed in these patients, this study is conducted to identify the prevalence of Intervertebral Disc Calcification (IDC) in thalassemia intermedia population.

METHODS: We investigated all the elder than 30 years beta-thalassemia intermedia patients of our Department thalassemia unit. Patients underwent thoracic and lumbar spinal X-rays for IDC presence. Patients presenting IDC were compared to those not presenting, regarding back pain anamnesis, presence of back pain, extramedullary hemopoiesis, sex, age, Hb levels, ferritin levels, reticulocytes, bilirubin values, thyroid-parathyroid abnormalities. Student's t-test was used to compare variables between patients with and without IDC. A P-value under 0.05 was considered statistically significant.

RESULTS: We investigated 30 beta-thalassemia intermedia patients (19 women) with an age range 38-61 yr (42.5 +/- 11.46 yr). Intervertebral disc calcifications were observed in seven patients (23.33%). No sex and laboratory parameters statistically significant differences were observed differences for IDC prevalence, while mean age and back pain history was statistically significantly different between the two groups.

CONCLUSIONS: In thalassemia patients, the big variety of spinal deformities may hide the presence of IDC and thus, this entity may be overlooked or underestimated. The clinical significance of IDC development as well as the possible prevention by early transfusion chelation therapy should be further investigated.}, } @article {pmid18027306, year = {2008}, author = {Schnitzler, C and Seifert, L and Ernwein, V and Chollet, D}, title = {Arm coordination adaptations assessment in swimming.}, journal = {International journal of sports medicine}, volume = {29}, number = {6}, pages = {480-486}, doi = {10.1055/s-2007-989235}, pmid = {18027306}, issn = {0172-4622}, mesh = {Adaptation, Physiological/*physiology ; Anthropometry ; Arm/*physiology ; Female ; France ; Humans ; Male ; Sex Factors ; Swimming/*physiology ; Videotape Recording ; }, abstract = {The link between modifications in arm coordination (IdC) and intracyclic velocity variation (IVV) as a function of swim pace and gender is investigated. Twelve elite swimmers performed 5 different swim paces. Video analysis allowed IdC determination. The IVV was determined with a velocity-metre system. Results showed (i) a significant increase in IdC with swim pace (p < 0.05) but no significant change in IVV, and (ii) a gender effect for the mean values of both IdC and IVV (p < 0.05). This suggests that (i) the increase in IdC with swimming velocity helps to maintain IVV stability, and (ii) the mean IdC and the IVV level are determined by the relationship between anthropometric parameters and mechanical power output. Indeed, compared to males, the females generally had a lower mechanical power output, and lower drag to overcome, which explains the lower IVV found. It was concluded that increasing IdC could be a strategy adopted by elite swimmers to maintain IVV at a constant level, despite increases in both propulsive and drag forces and in relation to individual characteristics. Thus, the IVV-IdC relationship may be an interesting tool to determine a swimmer's misadaptation to the swim pace and to orient individual coaching in coordination analysis.}, } @article {pmid18026874, year = {2008}, author = {Di Saverio, S and Gutierrez, J and Avisar, E}, title = {A retrospective review with long term follow up of 11,400 cases of pure mucinous breast carcinoma.}, journal = {Breast cancer research and treatment}, volume = {111}, number = {3}, pages = {541-547}, doi = {10.1007/s10549-007-9809-z}, pmid = {18026874}, issn = {0167-6806}, mesh = {Adenocarcinoma, Mucinous/*epidemiology/mortality/pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*epidemiology/mortality/pathology/therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; }, abstract = {BACKGROUND: Pure mucinous breast carcinoma (PMBC) is a rare histologic type of mammary neoplasm. It has been associated with a better short-term prognosis than infiltrating ductal carcinoma (IDC) but identical long-term survival curves have been reported. The value of tumor size for TNM staging has been challenged because of the mucin content of the lesions. This study presents a large PMBC series with 20 years follow up as compared to IDC. The relative significance of a variety of common prognostic factors is calculated for this uncommon histology.

MATERIALS AND METHODS: A retrospective analysis of all PMBC cases reported in the SEER database between 1973 and 2002 was conducted. Overall survival (OS) and disease specific survival (DSS) were calculated at 5, 10, 15 and 20 years of follow up. Those curves were compared with all the IDC cases reported into the database during the same period. The prognostic significance of gender, race, laterality, age at diagnosis, T and N status, estrogen and progesterone receptors and administration of radiation therapy was calculated by univariate and multivariate analysis.

RESULTS: There were 11,422 PMBC patients reported. The median age at diagnosis was 71 years (Range 25-85). Fifty three percent of the tumors were well differentiated, 38% were moderately differentiated and the remaining 9% were poorly differentiated or anaplastic. The majority of the tumors were located in the upper outer quadrant (44%) the other 56% were roughly evenly divided between the upper inner, lower inner, lower outer and central quadrants. Eighty six percent of the patients had only localized disease at the time of surgery without nodal or distant disease while 12% had regional nodal involvement and 2% had distant metastases. The PMBC cases showed a better differentiation with lesions of lesser grade and more frequent ER/PR expression, smaller size and lesser nodal involvement when compared to the IDC cases of the same period. Kaplan Meier survival curves revealed a 5 years. breast cancer specific survival rate of 94%. Although slowly decreasing with time, 10, 15 and 20 years survival were 89%, 85% and 81% respectively compared to 82% (5 year), 72% (10 year), 66% (15 year) and 62% (20 year) for IDC. There were no significant differences in overall survival. Multivariate analysis by Cox regression revealed the nodal status (N) to be the most significant prognostic factor followed by age, tumor size (T), progesterone receptors and nuclear grade. Disease specific survival curves stratified for nodal status revealed a highly significant difference between node negative and node positive patients. The addition of radiation therapy after surgery did not significantly improve overall survival.

CONCLUSIONS: This large retrospective comparative analysis confirms the less aggressive behavior of PMBC compared to IDC. This favorable outcome is maintained after 20 years. This tumor presents typically in older patients and is rarely associated with nodal disease. Positive nodal status appears to be the most significant predictor of worse prognosis.}, } @article {pmid18024331, year = {2007}, author = {Lee, Y and Cho, S and Seo, JH and Shin, BK and Kim, HK and Kim, I and Kim, A}, title = {Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast.}, journal = {American journal of clinical pathology}, volume = {128}, number = {6}, pages = {1041-1049}, doi = {10.1309/GA5VRFQFY5D0MVKD}, pmid = {18024331}, issn = {0002-9173}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/secondary ; Disease-Free Survival ; ErbB Receptors/*metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-3/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Survival Rate ; }, abstract = {The prognostic impact of epidermal growth factor receptor (EGFR) family members in breast carcinoma was evaluated through the analysis of 378 cases of invasive ductal carcinoma to determine the relationship between EGFR family members and clinical outcome. It was found that 13.8% of the cases were positive for erbB-3. Expression of erbB-3 was inversely correlated with EGFR and erbB-4 expression (P = .012 and P = .046). Expression of erbB-3 was correlated with positive estrogen and progesterone receptor status and inversely correlated with histologic grade. Expression of erbB-3 was correlated with longer disease-free survival (DFS; P = .028). Within the erbB-3-expressing group, there was a tendency for the coexpressing group to have shorter DFS compared with the single-expressing group. This study revealed that erbB-3 expression was associated with better prognosis. In an era of personalized targeted therapy, erbB-3 expression and its coexpressive pattern with other EGFR family members could be an important determinant for therapeutic plans for breast cancer treatment.}, } @article {pmid18022074, year = {2007}, author = {Rasmusson, KD and Stehlik, J and Brown, RN and Renlund, DG and Wagoner, LE and Torre-Amione, G and Folsom, JW and Silber, DH and Kirklin, JK and , }, title = {Long-term outcomes of cardiac transplantation for peri-partum cardiomyopathy: a multiinstitutional analysis.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {26}, number = {11}, pages = {1097-1104}, doi = {10.1016/j.healun.2007.08.002}, pmid = {18022074}, issn = {1557-3117}, mesh = {Adult ; Cardiomyopathies/etiology/*surgery ; Female ; Follow-Up Studies ; Graft Rejection ; *Heart Transplantation ; Humans ; Incidence ; Longitudinal Studies ; Male ; Outcome Assessment, Health Care/*statistics & numerical data ; *Postpartum Period ; Pregnancy ; Pregnancy Complications, Cardiovascular/*surgery ; Registries ; Survivors/statistics & numerical data ; }, abstract = {BACKGROUND: Outcomes of patients with a prior diagnosis of peri-partum cardiomyopathy (PPCM) undergoing heart transplantation are not well described but may be worse than for women who undergo transplantation for other etiologies.

METHODS: Between 1999 and 2005, 69 women aged younger than 40 underwent transplantation for PPCM in 29 institutions participating in the Cardiac Transplant Research Database. Patients with PPCM were compared with 90 female recipients of similar age with idiopathic dilated cardiomyopathy (IDC) and history of pregnancy (P+), 53 with no prior pregnancy (P-), and with 459 men of a similar age with IDC. Rejection, infection, cardiac allograft vasculopathy, and survival were compared.

RESULTS: Recipients with PPCM accounted for 1% of all transplants and 5% of transplants in women. Comparisons of the 4 patient groups were made. The risk of cumulative rejection was higher in the PPCM Group compared with the P- Group (p < 0.04) and the men (p < 0.0001). Cumulative risk of infection was lowest in the PPCM Group. Freedom from cardiac allograft vasculopathy was similar or higher in the PPCM Group compared with the other groups. Finally, the long-term survival of PPCM patients was comparable with the survival of men (p = 0.9), and there was a trend toward improved survival compared with the P+ Group (p = 0.07) and improved survival compared with the P- Group (p = 0.05).

CONCLUSIONS: Heart transplantation for PPCM remains relatively infrequent. Survival and freedom from cardiac allograft vasculopathy in patients who receive a transplant for PPCM are no worse than in women who require a transplant for other indications, regardless of parity.}, } @article {pmid18021691, year = {2007}, author = {Ruibal, A and Sánchez Salmón, A and Garrido, M and Bogdan Ciobotaru, A and Arias, JI}, title = {[Preoperative CA15.3 serum levels and cellular proliferation in patients having infiltrating ductal carcinomas of the breast].}, journal = {Revista espanola de medicina nuclear}, volume = {26}, number = {6}, pages = {367-371}, pmid = {18021691}, issn = {0212-6982}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood/*pathology/surgery ; Carcinoma, Ductal, Breast/*blood/*pathology/surgery ; Cell Proliferation ; Female ; Humans ; Middle Aged ; Mucin-1/*blood ; Preoperative Care ; }, abstract = {OBJECTIVE: To study the possible correlations between the preoperative CA15.3 serum levels and the cellular proliferation, measured by S-phase (SP), in patients having infiltrating ductal carcinomas (IDC) of the breast

MATERIAL AND METHODS: The study group included 79 patients with an age ranged between 39 and 86 yrs (64,8 +/- 11,8). Ploidy and S-phase were measured by cytometry (Fascam. Beckton Dikinson. USA) in fresh samples

RESULTS: Using as cut-off for SP the value of 7 %, which represents the median obtained previously in 321 patients with IDC (r: 0,8-51,2; 9,3 +/- 7,9; percentiles 25 y 75; 4,3 y 11,8 %), we can observed that the antigenic levels were higher (p:0,015) in the tumors with low SP. These same behavior was noted when 30U/ml was used as cut-off for CA15.3. Likewise, the levels of the tumor marker increased significantly (p:0,007) when the SP moved from < 4,3 % to 7,1 %, to decrease later (p:0,010) when the SP value was comprised between 7,11 % and 11,8 %. The same behavior of this tumor marker in relation to the SP was noted in tumors without axillary involvement tumors, as well as in aneuploid carcinomas.

CONCLUSION: a) Release of CA15.3 happens when SP increases to rise the 7,1 % value, to decrease later although that goes on increasing, and b) The same behaviour of this marker with the S-phase was observed in tumors without axillary involvement, as well as in aneuploid carcinomas.}, } @article {pmid18001417, year = {2007}, author = {McLean, SR and Shousha, S and Francis, N and Lim, A and Eccles, S and Nathan, M and Brock, CS and Palmieri, C}, title = {Metastatic ductal eccrine adenocarcinoma masquerading as an invasive ductal carcinoma of the male breast.}, journal = {Journal of cutaneous pathology}, volume = {34}, number = {12}, pages = {934-938}, doi = {10.1111/j.1600-0560.2007.00749.x}, pmid = {18001417}, issn = {0303-6987}, mesh = {Adenocarcinoma/metabolism/*pathology/therapy ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Bone Density Conservation Agents/therapeutic use ; Bone Neoplasms/secondary/therapy ; Breast Neoplasms, Male/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Cyclophosphamide/therapeutic use ; Diphosphonates/therapeutic use ; Eccrine Glands/*pathology ; Epirubicin/therapeutic use ; Fluorouracil/therapeutic use ; Humans ; Ibandronic Acid ; Immunohistochemistry ; Lung Neoplasms/secondary/therapy ; Lymphatic Metastasis/pathology ; Male ; Radiotherapy ; Sweat Gland Neoplasms/metabolism/*pathology/therapy ; Tamoxifen/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {We report the case of a 38-year-old man with metastatic ductal eccrine adenocarcinoma (DEA) of the left breast responding to 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. He initially presented with a 2-week history of difficulty walking because of bilateral hip and lower back pain. Examination showed an ulcerating cutaneous mass over the left anterior chest wall, left axillary lymphadenopathy and tenderness over the spine. A punch biopsy of the breast lesion resulted in a diagnosis of metastatic invasive ductal carcinoma (IDC) of the breast. He received palliative radiotherapy to the spine and also received six cycles of FEC chemotherapy and was subsequently commenced on tamoxifen and ibandronate. There was a symptomatic and radiological response to the FEC chemotherapy. Referral was subsequently made to our institution where the original punch biopsy was reviewed. This showed tumor cells that were polygonal with darkly stained pleomorphic nuclei and abundant eosinophilic cytoplasm and were also localized to areas of fibrotic stroma containing eccrine glands and ducts but did not appear to involve mammary tissue. Immunohistochemical studies showed the tumors to be cytokeratin 7 and gross cystic disease fluid protein-15/prolactin inducible protein negative and estrogen receptor alpha positive. Both the morphological and the immunohistochemical characteristics of the tumor were consistent with a revised diagnosis of DEA rather than IDC. When last reviewed, the patient remains pain free and his disease stable 17 months after his original presentation. This case emphasizes the challenge in discriminating histopathologically between two rare tumors of the male breast, namely DEA and IDC. In addition, clinical response to FEC by metastatic DEA has not been previously documented, and this therapeutic regimen warrants further investigation.}, } @article {pmid17986805, year = {2007}, author = {Horii, R and Akiyama, F and Ito, Y and Matsuura, M and Miki, Y and Iwase, T}, title = {Histological features of breast cancer, highly sensitive to chemotherapy.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {4}, pages = {393-400}, doi = {10.2325/jbcs.14.393}, pmid = {17986805}, issn = {1880-4233}, mesh = {Adenocarcinoma/*drug therapy/secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/secondary ; Chemotherapy, Adjuvant ; Epirubicin/administration & dosage ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Paclitaxel/administration & dosage ; }, abstract = {BACKGROUND: To establish tailor-made therapy for breast cancer, we investigated the possibility of predicting chemotherapy sensitive cases based on pre-therapeutic histological features.

METHODS: A total of 87 breast cancer patients underwent neoadjuvant chemotherapy with a paclitaxel (80 mg/m(2)/q1w, 12 courses)or an epirubicin regimen (90 mg/m(2)/q3wks, 4 courses). We investigated the chemo-sensitivity of invasive ductal carcinoma, solid-tubular carcinoma consisting of highly malignant cancer cells with many mitoses. We refer to this type of carcinoma as " chemo-sensitive carcinoma " and compared the histological therapeutic effects of chemo-sensitive and chemo-insensitive carcinomas.

RESULTS: 1) Out of 87 patients, 20 cases (23%) showed the histological features of chemo-sensitive carcinomas on pre-therapeutic needle biopsy specimens. The remaining 67 cases (77%) were classified as chemo-insensitive carcinoma. 2) Histologically marked or complete response were observed in 50% (10/20) of chemo-sensitive carcinomas and 10% (7/67) of chemo-insensitive carcinomas (chi(2)=15.33, p=0.0001). Multivariate analysis of chemo-sensitive carcinoma, including HER2, hormone receptor and p53 status, revealed that chemo-sensitive carcinoma had a significant correlation with the histological therapeutic effects (p=0.01119). 3) Pathological complete response (pCR) was achieved in 35% (7/20) of chemo-sensitive carcinomas and 1.5% (1/67)of chemo-insensitive carcinomas (chi(2)=20.71, p<0.0001). Multivariate analysis revealed that chemo-sensitive carcinoma had a significant correlation with pCR (p=0.0091).

CONCLUSION: The histological features of chemo-sensitive carcinoma were significant predictive factors for chemotherapeutic efficacy.}, } @article {pmid17985332, year = {2008}, author = {Parker, BS and Ciocca, DR and Bidwell, BN and Gago, FE and Fanelli, MA and George, J and Slavin, JL and Möller, A and Steel, R and Pouliot, N and Eckhardt, B and Henderson, MA and Anderson, RL}, title = {Primary tumour expression of the cysteine cathepsin inhibitor Stefin A inhibits distant metastasis in breast cancer.}, journal = {The Journal of pathology}, volume = {214}, number = {3}, pages = {337-346}, doi = {10.1002/path.2265}, pmid = {17985332}, issn = {0022-3417}, support = {R01 CA90291/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/analysis ; Bone Neoplasms/genetics/*metabolism/*secondary ; Breast Neoplasms/drug therapy/genetics/*metabolism ; Carcinoma, Ductal, Breast/drug therapy/genetics/*metabolism ; Case-Control Studies ; Cystatin A ; Cystatins/*analysis/genetics/metabolism ; Cysteine Proteinase Inhibitors/*analysis/genetics/metabolism ; Disease-Free Survival ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Injections, Intralesional ; Mice ; Neoplasm Invasiveness/pathology ; Prognosis ; Proportional Hazards Models ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Using the clinically relevant 4T1-derived syngeneic murine model of spontaneous mammary metastasis to bone, we have identified the cysteine cathepsin inhibitor Stefin A as a gene differentially expressed in primary and metastatic mammary tumours. In primary tumours, Stefin A expression correlated inversely with metastatic potential in 4T1-derived lines and was not detected in tumour cells in culture, indicating induction only within the tumour microenvironment. Enforced expression of Stefin A in the highly metastatic 4T1.2 cell line significantly reduced spontaneous bone metastasis following orthotopic injection into the mammary gland. Consistent with the mouse data, Stefin A expression correlated with disease-free survival (absence of distant metastasis) in a cohort of 142 primary tumours from breast cancer patients. This was most significant for patients with invasive ductal carcinoma expressing Stefin A, who were less likely to develop distant metastases (log rank test, p = 0.0075). In a multivariate disease-free survival analysis (Cox proportional hazards model), Stefin A expression remained a significant independent prognostic factor in patients with invasive ductal carcinoma (p = 0.0014), along with grade and progesterone receptor (PR) status. In human lung and bone metastases, we detected irregular Stefin A staining patterns, with expression often localizing to micrometastases (<0.2 mm) in direct contact with the stroma. We propose that Stefin A, as a cysteine cathepsin inhibitor, may be a marker of increased cathepsin activity in metastases. Using immunohistology, the cathepsin inhibitor was detected co-expressed with cathepsin B in lung and bone metastases in both the murine model and human tissues. We conclude that Stefin A expression reduces distant metastasis in breast cancer and propose that this may be due to the inhibition of cysteine cathepsins, such as cathepsin B.}, } @article {pmid17983063, year = {2007}, author = {Datrice, N and Narula, N and Maggard, M and Butler, J and Hsiang, D and Baick, C and Lane, K}, title = {Do breast columnar cell lesions with atypia need to be excised?.}, journal = {The American surgeon}, volume = {73}, number = {10}, pages = {984-986}, pmid = {17983063}, issn = {0003-1348}, mesh = {Breast/*pathology/*surgery ; Breast Neoplasms/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Retrospective Studies ; Risk Assessment ; }, abstract = {Columnar cell lesion with atypia (CCLA) is a newly recognized pathologic entity seen in breast specimens. The breast cancer risk associated with this finding is unclear, although CCLA had been found adjacent to both in situ and invasive carcinomas, but the incidence is unknown. Breast specimens from patients with a columnar cell lesion were reviewed by a pathologist for atypia. Twenty-one specimens with CCLA were identified [core biopsy (8), excisional biopsy (11), and simple mastectomy (2)]. Six of eight specimens with CCLA on core had adjacent abnormal pathology: infiltrating ductal carcinoma (IDC)/lobular carcinoma in situ (LCIS) (1), ductal carcinoma in situ (DCIS)/LCIS (1), DCIS (1), LCIS (1), and papillomatosis (2). Five of 11 specimens with CCLA on excisional biopsy had adjacent abnormal pathology: IDC (3), DCIS/LCIS (1), and atypical ductal hyperplasia/papilloma (1). Two of two simple mastectomy specimens had CCLA associated with IDC (1) and DCIS (1). Overall, abnormal pathology was found adjacent to CCLA in 62 per cent of specimens (13/21). Breast pathologic specimens containing a columnar cell lesion should be carefully examined for atypia. Surgical excision is warranted for CCLA found on core biopsy. The future risk of breast cancer based on the finding of CCLA alone requires further investigation.}, } @article {pmid17983059, year = {2007}, author = {Bremner, AK and Recabaren, J}, title = {The efficacy of MRI as an adjuvant to traditional mammography.}, journal = {The American surgeon}, volume = {73}, number = {10}, pages = {970-972}, pmid = {17983059}, issn = {0003-1348}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*statistics & numerical data ; Male ; Mammography/*statistics & numerical data ; Middle Aged ; }, abstract = {The objective of our study is to assess the utility of breast Magnetic Resonance Imaging (MRI) when used for indications other than those published in peer-reviewed studies. A retrospective chart review was conducted of the records of 588 women who underwent both mammography and breast MRI. Patients excluded from the study were those who had breast MRI for accepted indications based on published peer-review studies. Included on the study were the remaining 122 patients. An evaluation was then made in each case as to whether the MRI finding caused a change in the patient's management. In this review, subject age ranged from 27- to 85-years-old. The mean age of the sample was 54.5 years. Of the positive MRI results, 29 (27.7%) had additional findings. There were 25 (20.3%) subjects with a treatment change and 97 (79.5%) without. In conclusion, breast MRI affected the clinical management in 25 (20.3%) of 122 patients. The majority of the 25 patients have invasive ductal carcinoma, followed by ductal carcinoma in situ. We believe this is a significant percentage positively affected by the additional use of breast MRI. We suggest that indications for the use of breast MRI in addition to traditional breast imaging should include all patients with invasive ductal carcinoma.}, } @article {pmid17982668, year = {2007}, author = {Guo, CH and Koo, CY and Bay, BH and Tan, PH and Yip, GW}, title = {Comparison of the effects of differentially sulphated bovine kidney- and porcine intestine-derived heparan sulphate on breast carcinoma cellular behaviour.}, journal = {International journal of oncology}, volume = {31}, number = {6}, pages = {1415-1423}, pmid = {17982668}, issn = {1019-6439}, mesh = {Animals ; Breast Neoplasms/*pathology ; Cattle ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Female ; Heparitin Sulfate/analysis/metabolism/*pharmacology ; Humans ; Swine ; }, abstract = {Heparan sulphate is a sulphated glycosaminoglycan and is able to bind to and regulate the activity of many growth and signalling factors. We have previously shown that its expression is correlated with tumour grade and cell proliferation in breast phyllodes tumours. In this study, we examined the use of heparan sulphate as a biomarker of invasive ductal carcinoma and the effects of differentially sulphated heparan species on breast cancer cell behaviour. Immunohistochemistry using the 10E4 monoclonal antibody was carried out on 32 paraffin-embedded breast cancer specimens and paired non-cancerous breast tissues to compare the expression patterns of heparan sulphate. Upregulated expression of the sulphated 10E4 epitope in heparan sulphate was detected in both epithelial and stromal compartments of breast cancer compared with normal mammary tissues, with a 2.8X increase in immunoreactivity score. To determine the effects of differentially sulphated heparan sulphate molecules on breast cancer behaviour, cultured breast carcinoma cells were treated with chlorate, a competitive inhibitor of glycosaminoglycan sulphation, and two different heparan sulphate species. Inhibition of glycosaminoglycan sulphation resulted in a significant increase in cancer cell adhesion and a reduction in cell migration, together with upregulated expression of focal adhesion kinase and paxillin. Both porcine intestine- and bovine kidney-derived heparan sulphate species could block the change in cell adhesion. However, the former heparan sulphate species completely abolished, while the latter exacerbated, the chlorate-induced decrease in cell migration. The results show that heparan sulphate is a useful biomarker of breast invasive ductal carcinoma. Different sulphation patterns of heparan sulphate residues have differential effects in regulating breast cancer cellular behaviour, and this may be exploited to develop heparan sulphate into a useful target for treatment of breast carcinoma.}, } @article {pmid17982621, year = {2007}, author = {Wen, YH and Shi, X and Chiriboga, L and Matsahashi, S and Yee, H and Afonja, O}, title = {Alterations in the expression of PDCD4 in ductal carcinoma of the breast.}, journal = {Oncology reports}, volume = {18}, number = {6}, pages = {1387-1393}, pmid = {17982621}, issn = {1021-335X}, support = {K12CA01713/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis Regulatory Proteins/*genetics/metabolism ; Breast/cytology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/genetics/pathology ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; RNA-Binding Proteins/*genetics/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Programmed cell death 4 gene (PDCD4), an in vivo repressor of transformation, was originally isolated from a human glioma library by screening it with an antibody against a nuclear antigen in proliferating cells. PDCD4 functions as a transformation repressor by inhibiting the activity of the RNA helicase, eIF4A. We previously showed that retinoids, anti-estrogens and HER2/neu antagonist induce PDCD4 expression in human breast cancer cell lines. Very little is known about the expression of PDCD4 in human breast cancer tissues or the significance of the PDCD4 expression in breast cancer. To gain insight into the pattern of the PDCD4 expression in breast tissues, we performed an immunohistochemical analysis of the PDCD4 expression in 80 archived, normal and ductal breast carcinoma tissues (invasive and carcinoma in situ) (DCIS) and correlated PDCD4 expression with expression of known prognostic markers in breast cancer (ER, PR and HER2/neu). To assess the role of methylation on PDCD4 expression in breast cancer cells, breast cancer cell lines were treated with the demethylating agent 5-deoxy-azacytidine and analyzed for PDCD4 expression. We observed primarily nuclear localization of PDCD4 in ductal carcinoma in situ compared to normal breast tissues where the PDCD4 expression was predominantly cytoplasmic. This was seen more frequently in DCIS cases that were ER positive and HER2/neu negative samples. PDCD4 expression was markedly decreased in the invasive ductal carcinoma. We did not observe any significant relationship between PDCD4 expression and the expression of RAR or PR. In T-47D, MDA-MB-435 and MDA-MB-231 cells, treatment with 5-deoxy-azacytidine did not result in an increased expression of PDCD4. The present study demonstrated altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissues. In addition, there was a decreased expression of PDCD4 in breast cancer when compared with normal breast tissue. A loss of the PDCD4 expression in breast cancer cell lines does not appear to result from hypermethylation of the PDCD4 promoter.}, } @article {pmid17975961, year = {2007}, author = {de Miranda Marzullo, AC and Neto, OP and Bitar, RA and da Silva Martinho, H and Martin, AA}, title = {FT-raman spectra of the border of infiltrating ductal carcinoma lesions.}, journal = {Photomedicine and laser surgery}, volume = {25}, number = {5}, pages = {455-460}, doi = {10.1089/pho.2007.2094}, pmid = {17975961}, issn = {1549-5418}, mesh = {Breast Neoplasms/*chemistry/*pathology ; Carcinoma, Ductal, Breast/*chemistry/*pathology ; Case-Control Studies ; Female ; Humans ; Lasers, Solid-State ; *Spectrum Analysis, Raman ; }, abstract = {OBJECTIVE: The characterization of the FT-Raman spectra of the borders of lesions is of great importance in guiding the surgeon during surgical intervention.

BACKGROUND DATA: The main goals of this study were to investigate spectra of the borders of lesions of samples of infiltrating ductal carcinoma (IDC) and to determine the characteristics of these spectra.

METHODS: A total of 93 spectra were collected from five samples of healthy tissues and from 13 samples of IDC breast tissues using FT-Raman spectroscopy. Cluster analysis was used to separate the spectra into different groups. The results obtained from the statistical analysis were confirmed by a histopathological analysis.

RESULTS: The results showed that 17 out of the 67 spectra collected from the IDC samples demonstrated wide variety. The only significant difference between the peaks of the spectra of normal tissues and those of lesion borders is a peak at 538 cm(1) . This peak is related to disulfide bridges in cysteine, and it seems to be the main factor for the FT-Raman determination of the boundaries between healthy and pathological tissue.

CONCLUSIONS: These results serve as a foundation for future studies and application of Raman spectroscopy for optical diagnosis to guide biopsy and surgical intervention.}, } @article {pmid17969083, year = {2007}, author = {He, Q and Shkarin, P and Hooley, RJ and Lannin, DR and Weinreb, JC and Bossuyt, VI}, title = {In vivo MR spectroscopic imaging of polyunsaturated fatty acids (PUFA) in healthy and cancerous breast tissues by selective multiple-quantum coherence transfer (Sel-MQC): a preliminary study.}, journal = {Magnetic resonance in medicine}, volume = {58}, number = {6}, pages = {1079-1085}, doi = {10.1002/mrm.21335}, pmid = {17969083}, issn = {0740-3194}, support = {R01 CA109471-01 A1/CA/NCI NIH HHS/United States ; R21CA80906/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Biomarkers, Tumor/*metabolism ; Breast/*metabolism ; Breast Neoplasms/*diagnosis/*metabolism ; Fatty Acids, Unsaturated/*metabolism ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Magnetic Resonance Spectroscopy/*methods ; Middle Aged ; Pilot Projects ; Tissue Distribution ; }, abstract = {The spatial distribution of polyunsaturated fatty acids (PUFA) in healthy and cancerous human breast tissues was measured in vivo with a selective multiple-quantum coherence transfer (Sel-MQC) technique. This method selectively detected the olefinic methylene protons (-CH = CH-) of PUFA at 5.3 ppm that were coupled with allylic methylene protons (-CH(2)-CH(2)-CH=) of unsaturated acyl chain at 2.8 ppm. Unwanted lipid coherences and tissue water signal were dephased in a single scan. Breast PUFA were mapped at 1 cm(3) voxel resolution in sagittal slices of nine breasts in six healthy female volunteers that were compared to invasive ductal carcinoma (IDC) in one breast cancer patient. The healthy breast tissue displayed continuous PUFA distribution. In some individuals, PUFA appeared throughout the breast tissue; in others they were only located in the central breast area. Decreased PUFA levels were detected in the IDC of the breast cancer patient. The magnetic resonance spectroscopic imaging (MRSI) measurement was consistent with the histological findings, ultrasound, and mammography images. PUFA patterns are sensitive to abnormal breast tissue changes including malignant transformations, and thus may serve as a biomarker for early diagnosis and therapeutic monitoring of breast disease.}, } @article {pmid17957053, year = {2007}, author = {Kang, DK and Jeon, GS and Yim, H and Jung, YS}, title = {Diagnosis of the intraductal component of invasive breast cancer: assessment with mammography and sonography.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {26}, number = {11}, pages = {1587-1600}, doi = {10.7863/jum.2007.26.11.1587}, pmid = {17957053}, issn = {0278-4297}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal/*diagnostic imaging ; Female ; Humans ; Image Enhancement/methods ; Mammography/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Subtraction Technique ; Ultrasonography, Mammary/methods ; }, abstract = {OBJECTIVE: The aim of this study was to investigate mammographic and sonographic features and their sensitivities for depiction of the intraductal component associated with invasive ductal carcinoma (IDC).

METHODS: During a 1-year period, 132 patients with IDC underwent surgical treatment. All patients underwent mammography and high-resolution sonography, and the findings were reported according to the American College of Radiology's Breast Imaging Reporting and Data System lexicon. Tumors were classified as "pure IDC" and "IDC with an intraductal component" by histopathologic evaluation. We compared mammographic and sonographic features between the above 2 groups and attempted to correlate them with histopathologic findings. We also investigated separate and combined sensitivities, specificities, and accuracies of both mammography and breast sonography for showing intraductal components. Finally, imaging measurements were compared with pathologic measurements.

RESULTS: One hundred four (79%) of the 132 IDCs contained an intraductal component. Patients with IDC with an intraductal component showed calcifications on mammography and showed an echogenic halo, duct dilatation, calcifications, and increased vascularity in surrounding tissue on sonography more frequently than patients with pure IDC. The sensitivities of mammography, sonography, and their combined assessment for detection of an intraductal component were 55%, 80%, and 86%, respectively. The combined assessment (r = 0.90) measured the extent of the tumor more accurately than mammography (r = 0.71) or sonography (r = 0.79) separately.

CONCLUSIONS: Combined assessment with mammography and sonography offers more accurate information for the presence of an intraductal component and the extent of a tumor than each separate assessment.}, } @article {pmid17954264, year = {2007}, author = {Walker, LC and Harris, GC and Holloway, AJ and McKenzie, GW and Wells, JE and Robinson, BA and Morris, CM}, title = {Cytokeratin KRT8/18 expression differentiates distinct subtypes of grade 3 invasive ductal carcinoma of the breast.}, journal = {Cancer genetics and cytogenetics}, volume = {178}, number = {2}, pages = {94-103}, doi = {10.1016/j.cancergencyto.2007.06.002}, pmid = {17954264}, issn = {0165-4608}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics ; Cohort Studies ; DNA, Complementary ; Female ; Humans ; Keratin-18/*genetics ; Keratin-8/*genetics ; Middle Aged ; Neoplasm Invasiveness/*genetics ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Invasive ductal carcinomas of the breast (IDC) are routinely assessed on hematoxylin and eosin stained paraffin sections, with limited use of immunohistochemistry (IHC). Most IDC are regarded as a single diagnostic entity, IDC of no special type (IDC-NST), which is subdivided further only by grading. However, recent research suggests that there is high clinical relevance in differentiating IDC subtypes. Here, we ascertain whether tumor histology alone can predict basal or luminal cell phenotype in high-grade IDC-NST, and whether IHC and molecular characteristics are associated with the observed morphologies. A total of 29 grade 3 IDC-NST samples were studied, 10 tumors from a selected pilot cohort A and 19 tumors from an unselected validation cohort B. Along with histopathological assessment, the expression of ESR1, PGR, ERBB2 (HER-2), the basal/myoepithelial marker TP73L (p63), cytokeratins 5/6 (KRT5/6) and 14 (KRT14), and the luminal-specific cytokeratins 8/18 (KRT 8/18) and 19 (KRT19) was assessed by IHC. Hierarchical cluster analysis of clinicopathological variables and, separately, microarray expression profiles showed that the phenotypically distinctive basaloid and luminal tumors of cohort A fell into two main groups, defined by heterogeneous or uniformly positive expression of KRT8/18. The 38 genes differentially expressed between these two classes included ERBB2, KRT8, and six other genes previously associated with ERBB2-positive or luminal phenotypes. Tumor histology was not predictive for validation cohort B, but quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed two molecularly defined clusters that again aligned with the KRT8/18 staining phenotypes. Metaphase comparative genomic hybridization revealed 10q, 16q, and 20q copy-number imbalances that associated recurrently with KRT8/18 staining patterns.}, } @article {pmid17949880, year = {2008}, author = {Staub, G and Fitoussi, A and Falcou, MC and Salmon, RJ}, title = {[Breast cancer surgery: use of mammaplasty. Results. Series of 298 cases].}, journal = {Annales de chirurgie plastique et esthetique}, volume = {53}, number = {2}, pages = {124-134}, doi = {10.1016/j.anplas.2007.05.012}, pmid = {17949880}, issn = {1768-319X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Female ; Humans ; Mammaplasty/adverse effects/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {Breast cancer surgery has long consisted in the sole use of mastectomy. Then, it was proved that, in terms of global survival, conservative treatments associated with radiotherapies could give the same results. But breast deformations due to classic conservative treatments led some authors to use plastic surgery procedures: breast plastic surgery. Some breast plastic surgery procedures are well-known, others have been adapted to breast cancer treatment and more particularly in case of tumor of superior and internal quadrants. After the retrospective analysis of a series of 298 cases from the Institute Curie, the aim of this survey is to find whether there is a difference between: breast plastic surgery and usual treatments like mastectomy and classic conservative treatments. For most cases, the tumors were invasive ductal carcinoma and T2N0M0 carcinoma. This survey showed, among these cases, 94.56% of global survival, 86.81% of survival without metastasis and a five-year 93.47% without local recurrence, which is comparable to the results for mastectomies and classic conservative treatments. In selected cases, the use of mammaplasty could be interesting for breast cancer surgery treatment.}, } @article {pmid17949231, year = {2007}, author = {Kamali-Sarvestani, E and Aliparasti, MR and Atefi, S}, title = {Association of interleukin-8 (IL-8 or CXCL8) -251T/A and CXCR2 +1208C/T gene polymorphisms with breast cancer.}, journal = {Neoplasma}, volume = {54}, number = {6}, pages = {484-489}, pmid = {17949231}, issn = {0028-2685}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Case-Control Studies ; Disease Progression ; Female ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-8/*genetics ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Interleukin-8B/*genetics ; }, abstract = {A case-control study involving 257 breast cancer patients with invasive ductal carcinoma and 233 healthy women was carried out to explore if the IL-8 -251T/A polymorphism and the CXCR2 +1208 C/T polymorphism have a role in breast cancer susceptibility. Genotypic analysis showed an increased frequency of high producer IL-8 -251AA genotype (p=0.016) in the patient group as compared to controls while CXCR2 +1208 C/T polymorphism did not show any differences between studied groups. However, in contrast to IL-8 -251 polymorphism, the percentage of CXCR2 +1208 TT genotype was significantly lower in patients with NPI3.4 (2% and 12%, respectively; p=0.03). Also, ER- tumors showed an approximately significant higher CXCR2 +1208 TT genotype compared to ER+ tumors (18.6% and 7.1%, respectively; p=0.07). In conclusion, IL-8 -251T/A polymorphism is associated with development of invasive ductal carcinoma type of breast cancer while CXCR2 +1208C/T polymorphism may affect the disease progression.}, } @article {pmid17948023, year = {2008}, author = {Dillon, MF and Maguire, AA and McDermott, EW and Myers, C and Hill, AD and O'Doherty, A and Quinn, CM}, title = {Needle core biopsy characteristics identify patients at risk of compromised margins in breast conservation surgery.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {21}, number = {1}, pages = {39-45}, doi = {10.1038/modpathol.3800975}, pmid = {17948023}, issn = {0893-3952}, mesh = {Biopsy, Needle ; Breast Neoplasms/*pathology/surgery ; Calcinosis/pathology ; Carcinoma, Ductal, Breast/*pathology/surgery ; Cohort Studies ; Female ; Humans ; Logistic Models ; *Mastectomy, Segmental ; Necrosis ; Neoplasm Invasiveness ; Odds Ratio ; *Patient Selection ; Reoperation ; Risk Assessment ; Treatment Failure ; Treatment Outcome ; }, abstract = {Selection of patients for breast-conserving surgery relies on inexact parameters such as the preoperative estimation of lesion size. This study investigates the value of needle core biopsy findings, in particular, the relative quantity of DCIS, in improving patient selection for breast conservation. Patients undergoing breast-conserving surgery for invasive ductal carcinoma from 1999 to 2004 were identified. Only patients who had a preoperative diagnosis of carcinoma (DCIS and invasive) on core biopsy were included. All core biopsies were reviewed by a breast histopathologist to document the quantity and characteristics of the DCIS component. Of a total of 281 patients, 46% (n=129) had invasive disease on core biopsy (group 1) and 54% (n=152) had either invasive disease with an accompanying DCIS component or DCIS only on core biopsy (group 2). The compromised margin rate for group 1 was 23% compared to 39% for group 2 (P=0.004). The rate of compromised margins increased progressively as the core biopsy DCIS component increased until a rate of 75% (n=18/24) was reached in patients with DCIS only on core biopsy. In patients with a DCIS component on core biopsy, the presence of necrosis (P=0.002), solid type architecture (P=0.008), high grade DCIS (P=0.007), calcification (P=0.003), and the relative proportion of DCIS present (P<0.001) were associated with compromised margins on univariate analysis. On multivariate analysis of this subgroup, the proportion of DCIS in this subgroup (P=0.048) was an independent predictor of compromised margins. The presence and relative proportion of DCIS on core biopsy provides important information as to whether patients are at risk of compromised margins. Documentation of these parameters may assist patient selection for breast-conserving surgery or identify patients who may benefit from wider margins at the time of initial operation.}, } @article {pmid17946832, year = {2006}, author = {Hoyer, D and Frank, B and Götze, Ch and Baranowski, R and Zebrowski, JJ and Vallverdú, M and Palacios, M and Caminal, P and Bayés de Luna, A and Stein, PK and Schmidt, G and Schmidt, H}, title = {Association between short term and long term communication in pathological autonomic control.}, journal = {Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference}, volume = {2006}, number = {}, pages = {433-436}, doi = {10.1109/IEMBS.2006.260858}, pmid = {17946832}, issn = {1557-170X}, mesh = {Autonomic Nervous System/*physiopathology ; Autonomic Nervous System Diseases/diagnosis/*physiopathology ; *Biological Clocks ; Cardiovascular Diseases/diagnosis/*physiopathology ; Computer Simulation ; Feedback ; Humans ; *Models, Biological ; }, abstract = {Autonomic Information Flow (AIF) reflects the time scale dependence of autonomic communications such as vagal, sympathetic, and slower rhythms and their complex interplay. We investigated the hypothesis that pathologically disturbed short term control is associated with simplified complex long term control. This particular characteristic of altered autonomic communication was evaluated in different medical patient groups. Holter recordings were assessed in patients with multiple organ dysfunction (MODS) (26 survivors, 10 non-survivors); with heart failure (14 low risk-without history of aborted cardiac arrest (CA), 13 high risk--with history of CA); with idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk of CA), after myocardial infarction (MI) (1221 low risk--survivors, 55 high risk--non-survivors); after abdominal aorta surgery (AAS, 32 length of stay in hospital LOS>7 days, 62 LOS < or =7 days). AIF of short and long time scales was investigated. We found a fundamental association of increased short term randomness and decreased long term randomness due to pathology. Concerning risk, high risk patients were characterized by increased short term complexity and decreased long term complexity in all patients groups with the exception of the IDC patients. We conclude that different time scales of AIF represent specific pathophysiological aspects of altered autonomic communication and control. The association of altered short term control with simplified long term behavior might be a pathophysiologically relevant compensation mechanism in the case of a disturbed fastest actuator. This knowledge might be useful for the development of comprehensive therapeutic strategies besides the predictive implications.}, } @article {pmid17945020, year = {2007}, author = {Arkadianos, I and Valdes, AM and Marinos, E and Florou, A and Gill, RD and Grimaldi, KA}, title = {Improved weight management using genetic information to personalize a calorie controlled diet.}, journal = {Nutrition journal}, volume = {6}, number = {}, pages = {29}, pmid = {17945020}, issn = {1475-2891}, mesh = {Adult ; Analysis of Variance ; Blood Glucose/analysis/*metabolism ; Body Mass Index ; Diet, Mediterranean ; Diet, Reducing ; Exercise/physiology ; Female ; Genetic Predisposition to Disease ; Genotype ; Glycemic Index ; Humans ; Male ; Middle Aged ; Nutrigenomics/*methods ; Nutritional Requirements ; Obesity/*diet therapy/*genetics ; Patient Compliance ; Time Factors ; Treatment Outcome ; *Weight Loss ; }, abstract = {BACKGROUND: Gene-environment studies demonstrate variability in nutrient requirements depending upon individual variations in genes affecting nutrient metabolism and transport. This study investigated whether the inclusion of genetic information to personalize a patient's diet (nutrigenetics) could improve long term weight management.

METHODS: Patients with a history of failures at weight loss were offered a nutrigenetic test screening 24 variants in 19 genes involved in metabolism. 50 patients were in the nutrigenetic group and 43 patients attending the same clinic were selected for comparison using algorithms to match the characteristics: age, sex, frequency of clinical visits and BMI at initial clinic visit. The second group of 43 patients did not receive a nutrigenetic test. BMI reduction at 100 and > 300 days and blood fasting glucose were measured.

RESULTS: After 300 days of follow-up individuals in the nutrigenetic group were more likely to have maintained some weight loss (73%) than those in the comparison group (32%), resulting in an age and gender adjusted OR of 5.74 (95% CI 1.74-22.52). Average BMI reduction in the nutrigenetic group was 1.93 kg/m2(5.6% loss) vs. an average BMI gain of 0.51 kg/m2(2.2% gain) (p < 0.023). Among patients with a starting blood fasting glucose of > 100 mg/dL, 57% (17/30) of the nutrigenetic group but only 25% (4/16) of the non-tested group had levels reduced to < 100 mg/dL after > 90 days of weight management therapy (OR for lowering glucose to < 100 mg/dL due to diet = 1.98 95%CI 1.01, 3.87, p < 0.046).

CONCLUSION: Addition of nutrigenetically tailored diets resulted in better compliance, longer-term BMI reduction and improvements in blood glucose levels.}, } @article {pmid17944949, year = {2008}, author = {Sauer, T and Karimzadeh, M}, title = {Characteristic cytological features of histological grade one (G1) breast carcinomas in fine needle aspirates.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {19}, number = {5}, pages = {287-293}, doi = {10.1111/j.1365-2303.2007.00521.x}, pmid = {17944949}, issn = {1365-2303}, mesh = {Aged ; *Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Female ; Humans ; }, abstract = {OBJECTIVE: To analyse the spectrum of nuclear features as well as dissociation pattern found in fine needle aspirates (FNAC) from histological grade 1 breast carcinomas and evaluate the critical cytological features of these lesions.

MATERIAL AND METHODS: The material consisted of FNAC smears from 494 histologically confirmed grade 1 breast carcinomas. All smears were revaluated for cell dissociation pattern, nuclear size, cell uniformity, nucleoli, nuclear margin and chromatin pattern. All features were compared with the histological subtype and cytological grading.

RESULTS: 73.9% of the cases were cytological grade 1, 24.3% were grade 2 and 1.8% were grade 3. The majority of the cases had a cell dissociation pattern showing both a population of single carcinoma cells and cell clusters (65.9%). Practically all tumours had a granular chromatin pattern (94.7%) and a slightly irregular nuclear margin with folds and grooves (94%) irrespective of histological subtype and cytological grading. Nucleoli were mostly indistinct or small (74%), whereas 24.3% were noticeable and 1.7% abnormal. Practically all cases revealed some degree of pleomorphism with 74.3% showing mild and 22.4% a distinct pleomorphism. A small subgroup of IDC was classified as monomorphic (3.3%). Almost all tumours had nuclear sizes in the range of 2-4 x RBC (96.9%).

CONCLUSION: Not all histological grade 1 carcinomas are cytological grade 1. About 25% were grade 2, and a small subpopulation reached grade 3. The typical/average findings in FNAC from grade 1 breast carcinomas were a population of both groups and single cells showing mild pleomorphism, granular chromatin, slightly irregular nuclear margin, indistinct nucleolus and nuclear size 2-4 x RBC.}, } @article {pmid17942347, year = {2007}, author = {Godoy, GP and da Silveira, EJ and Lins, RD and de Souza, LB and de Almeida Freitas, R and Queiroz, LM}, title = {Immunohistochemical profile of integrins in enlarged dental follicles and dentigerous cysts.}, journal = {Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics}, volume = {104}, number = {6}, pages = {e29-34}, doi = {10.1016/j.tripleo.2007.05.024}, pmid = {17942347}, issn = {1528-395X}, mesh = {Dental Sac/chemistry/diagnostic imaging/*pathology ; Dentigerous Cyst/chemistry/diagnostic imaging/*pathology ; Humans ; Integrins/*analysis ; Radiography ; Staining and Labeling/methods ; }, abstract = {OBJECTIVE AND STUDY DESIGN: The morphological distinction between incipient dentigerous cyst (IDC) and enlarged pericoronal dental follicle (EDF) remains one of the most controversial questions in the literature. The objective of this study was to analyze the immunohistochemistry expression of alfa(2)beta(1), alfa(3)beta(1), and alfa(5)beta(1) in 23 cases of EDFs and 21 cases of IDCs.

RESULTS: All integrins were immunopositive in the cases studied. A significant difference was detected regarding alfa(2)beta(1) integrin (P < .0001) in which a higher expression was present in IDCs. Moreover, statistical difference was also found between basal and suprabasal cell layer in cystic epithelium (P < .0034). The alfa(3)beta(1) integrin expression showed significant difference (P < .013) between EDF and IDC with a tendency of more pronounced staining in IDC.

CONCLUSIONS: These results corroborate the possibility of histopathological distinction between EDF and IDC in which squamous metaplasia of reduced enamel epithelium to stratified epithelium would be the first event of cystic transformation.}, } @article {pmid17940995, year = {2007}, author = {Ohuchida, K and Mizumoto, K and Miyasaka, Y and Yu, J and Cui, L and Yamaguchi, H and Toma, H and Takahata, S and Sato, N and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis.}, journal = {The Journal of pathology}, volume = {213}, number = {3}, pages = {275-282}, doi = {10.1002/path.2250}, pmid = {17940995}, issn = {0022-3417}, mesh = {Biomarkers, Tumor/analysis ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Cell Differentiation ; Cell Line, Tumor ; Chemotactic Factors/analysis/*genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Pancreas/chemistry ; Pancreatic Neoplasms/metabolism/*pathology ; Paraffin Embedding ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; S100 Proteins/analysis/*genetics/metabolism ; }, abstract = {Controversy exists regarding the clinical significance of S100A2 in the progression of tumours. In pancreatic cancer, little is known about the role of S100A2. The aim of this study was to clarify the clinical significance of S100A2 expression in pancreatic carcinogenesis. We microdissected invasive ductal carcinoma (IDC) cells from 22 lesions, pancreatic intraepithelial neoplasia (PanIN) cells from five lesions, intraductal papillary mucinous neoplasm (IPMN) cells from 38 lesions, pancreatitis-affected epithelial (PAE) cells from 16 lesions, and normal ductal cells from 18 normal pancreatic tissues. S100A2 expression in 14 pancreatic cancer cell lines, microdissected cells and formalin-fixed paraffin-embedded (FFPE) samples was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Microdissection analyses revealed that IDC cells expressed higher levels of S100A2 than did IPMN, PAE or normal cells (all comparisons, p < 0.007). Cell lines from metastatic sites expressed higher levels of S100A2 than those from primary sites. PanIN cells expressed higher levels of S100A2 than normal cells (p = 0.018). IDC cells associated with poorly differentiated adenocarcinoma expressed higher levels of S100A2 than did IDC cells without poorly differentiated adenocarcinoma (p = 0.006). Analyses of FFPE samples revealed that levels of S100A2 were higher in samples from patients who survived < 1000 days after surgery than in those from patients who survived > 1000 days (p = 0.043). Immunohistochemical analysis was consistent with qRT-PCR. S100A2 may be a marker of tumour progression or prognosis in pancreatic carcinogenesis and pancreatic cancer.}, } @article {pmid17940394, year = {2007}, author = {Iida, S and Furukawa, K and Yokoyama, T and Yanagihara, K and Iwasaki, R and Noguchi, T and Tsuchiya, S and Sugisaki, Y and Naito, Z and Tajiri, T}, title = {[A case of elderly metastatic breast cancer with a complete response to treatment with capecitabine and cyclophosphamide].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {10}, pages = {1697-1700}, pmid = {17940394}, issn = {0385-0684}, mesh = {Aged ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Cyclophosphamide/administration & dosage ; Deoxycytidine/administration & dosage/*analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil/administration & dosage/*analogs & derivatives ; Humans ; Lymphatic Metastasis ; Neoplasm Metastasis ; Treatment Outcome ; }, abstract = {We report a case of elderly metastatic breast cancer with a complete response to the treatment with XC (X: capecitabine and C: cyclophosphamide). A 78-year-old woman, who presented with left breast cancer, underwent pectoralis-preserving mastectomy when she was 76 years old. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), pT1c (2.0 cm), n (1/10), ly3, v1, ER (-), PgR (-), HER2: score 1. After one year and a half, a left supraclavicular lymph node metastasis, a left interpectoral lymph node metastasis, and mediastinal lymph nodes metastasis were noted. Capecitabine and cyclophosphamide were administered as first-line chemotherapy. After 8 cycles, all metastases responded, and this therapy is now being continued (19 cycles) on an outpatient basis. The complete response has continued for nine months. XC therapy can be the first-line chemotherapy for elderly metastatic breast cancer patients since it has been effective and no serious side effects have been encountered while maintaining quality of life.}, } @article {pmid17940391, year = {2007}, author = {Murakami, K and Sakata, H and Miyazawa, Y and Matsushita, K and Akutsu, Y and Nishimori, T and Yoneyama, Y and Usui, A and Kano, M and Matsubara, H and Ochiai, T}, title = {[Two cases treated with trastuzumab as primary chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {10}, pages = {1683-1687}, pmid = {17940391}, issn = {0385-0684}, mesh = {Adult ; Antibodies, Monoclonal/*administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/secondary ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Female ; Humans ; Paclitaxel/administration & dosage ; Trastuzumab ; }, abstract = {We report two cases treated with primary chemotherapy containing trastuzumab with a review of some important papers. The first patient was a 43-year-old female. A 33-mm left breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC)) with several lymph node metastases in the Ax, Ic and Sc was found. After primary chemotherapy with 6 courses of EC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy for the local tumor was judged as PR. However, brain metastases appeared, so the operation was canceled. Brain metastases were then treated by gamma-knife three times, but systemic chemotherapy was not administered. Eight months later, carcinomatous meningitis appeared. Intrathecal chemotherapy with MTX+Ara-C was started, but the patient died after 20 months from the beginning of the treatment. Local efficacy was judged as CR. The second patient was a 41-year-old female. A 39-mm right breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC)) with two lymph node metastases in the Ax was found. After primary chemotherapy with 6 courses of FEC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy was judged as PR. The operation was scheduled, but he patient wished to continue chemotherapy for cosmetic reasons. Later, because of mild tumor regrowth, we used 2 courses of vinorelbine in combination with trastuzumab. The tumor grew more, so Bp + Ax was done. The woman is alive at this writing with no recurrence.}, } @article {pmid17940078, year = {2007}, author = {Lee, A and Park, WC and Yim, HW and Lee, MA and Park, G and Lee, KY}, title = {Expression of c-erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast.}, journal = {Japanese journal of clinical oncology}, volume = {37}, number = {9}, pages = {708-714}, doi = {10.1093/jjco/hym082}, pmid = {17940078}, issn = {1465-3621}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Cyclin D1/*metabolism ; Down-Regulation ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Survival Analysis ; Time Factors ; Up-Regulation ; }, abstract = {BACKGROUND: C-erbB2 and estrogen receptors (ER) are well known for their cell proliferative capacity. Cyclin D1 is a major downstream target of both c-erbB2 and ER. This study was designed to analyze the expression of c-erbB2, cyclin D1 and ER and their prognostic implications in invasive ductal carcinoma of the breast.

METHODS: The c-erbB2 status was evaluated by fluorescence in situ hybridization and immunohistochemistry (IHC) and cyclin D1 and ER were evaluated by IHC in 333 invasive breast cancer specimens.

RESULTS: The results of FISH and IHC for c-erbB2 showed 86.7% concordance. The overexpression of c-erbB2 was associated with the high expression of cyclin D1 and the negative expression of ER (P < 0.01 for both). The high expression of cyclin D1 was associated with the positive expression of ER (P < 0.01). When the group of patients who overexpressed c-erbB2 were analyzed, the patients with the low expression of cyclin D1 showed a significantly higher mortality than those with the high expression of cyclin D1 (RR = 3.2; 95% CI, 1.6-6.6). When the group of the high cyclin D1 expression was analyzed, the patients with negative expression of ER showed a significantly higher mortality than those with the positive expression of ER (RR = 2.1; 95% CI, 1.1-3.8).

CONCLUSIONS: Higher expression of cyclin D1 was associated with better prognosis in patients with c-erbB2 overexpression, and positive expression of ER was associated with better prognosis in patients with high cyclin D1 expression.}, } @article {pmid17936526, year = {2007}, author = {Cluzel-Tailhardat, M and Bonnet-Duquennoy, M and de Queral, DP and Vocanson, M and Kurfürst, R and Courtellemont, P and Le Varlet, B and Nicolas, JF}, title = {Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells.}, journal = {Toxicology letters}, volume = {174}, number = {1-3}, pages = {98-109}, doi = {10.1016/j.toxlet.2007.08.015}, pmid = {17936526}, issn = {0378-4274}, mesh = {Allergens/*toxicity ; Cells, Cultured ; Dendritic Cells/*drug effects/immunology ; Dinitrofluorobenzene/analogs & derivatives/toxicity ; Eugenol/analogs & derivatives/toxicity ; Gene Expression Profiling ; Haptens/*toxicity ; Humans ; Oligonucleotide Array Sequence Analysis ; Sodium Dodecyl Sulfate/toxicity ; Terpenes/toxicity ; }, abstract = {A critical step in the induction of allergic contact dermatitis is the interaction of haptens with immature dendritic cells (iDC) leading to their activation. Therefore iDC appear as suitable targets for the evaluation of the sensitizing properties of haptens with the aim of developing in vitro toxicologic methods. Here, using a low-density cDNA-array, we analyzed the expression of 165 genes related to dendritic cell biology in human iDC following a 24h incubation with four haptens representative of strong (DNBS), moderate (isoeugenol) and weak (eugenol, hydroxycitronellal) contact sensitizers and with one irritant sodium dodecyl sulphate (SDS). Results show that 21/165 iDC genes were significantly modulated by hapten treatment. Some genes were preferentially modulated by a given chemical. Thus, DNBS, isoeugenol, eugenol and hydroxycitronellal consistently modulated CCR5, CCL27, CCL2 and CCR7, respectively, whereas the CXCL10 gene was regulated by SDS. When subjected to principal component analysis, the 21 target genes fell into four groups associated with a particular type of chemical endowed with distinct sensitizing or irritant properties. Thus, gene profiling of iDC using low-density microarray allows, for screening of chemicals, the indentification of weak haptens with potential skin sensitizing properties. These results suggest that gene profiling of iDC using low-density microarrays may be useful to identify chemicals with weak skin sensitizing properties.}, } @article {pmid17936522, year = {2007}, author = {Bezić, J and Forempoher, G and Poljicanin, A and Gunjaca, G}, title = {Apocrine adenoma of the breast coexistent with invasive carcinoma.}, journal = {Pathology, research and practice}, volume = {203}, number = {11}, pages = {809-812}, doi = {10.1016/j.prp.2007.07.001}, pmid = {17936522}, issn = {0344-0338}, mesh = {Adenoma, Sweat Gland/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Multiple Primary/metabolism/*pathology ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Sweat Gland Neoplasms/metabolism/*pathology ; }, abstract = {We describe a case of apocrine adenoma with simultaneous occurrence of invasive ductal carcinoma in the breast of a 53-year-old woman. Apocrine adenoma affecting the breast is very rare. The lesion is composed of back-to-back ducts and papillary fronds covered with apocrine cells, and it is sharply demarcated from the surrounding breast tissue. The patient presented with a palpable nodule with skin retraction in her right breast, where ultrasound examination identified a 5-mm hypoechogenic nodule. The ultrasound also revealed in the surrounding breast parenchyma an additional abnormal finding suggestive of carcinoma. Histologic examination of the excised specimen showed that the hypoechogenic nodule represented an apocrine adenoma in proximity to the invasive ductal breast carcinoma. This is the first report that describes the simultaneous occurrence of these two lesions in the same breast.}, } @article {pmid17934221, year = {2007}, author = {Chainais, P}, title = {Infinitely divisible cascades to model the statistics of natural images.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {29}, number = {12}, pages = {2105-2119}, doi = {10.1109/TPAMI.2007.1113}, pmid = {17934221}, issn = {0162-8828}, mesh = {*Algorithms ; *Artificial Intelligence ; Computer Simulation ; Data Interpretation, Statistical ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; *Models, Statistical ; Pattern Recognition, Automated/*methods ; }, abstract = {We propose to model the statistics of natural images thanks to the large class of stochastic processes called Infinitely Divisible Cascades (IDC). IDC were first introduced in one dimension to provide multifractal time series to model the so-called intermittency phenomenon in hydrodynamical turbulence. We have extended the definition of scalar infinitely divisible cascades from 1 to N dimensions and commented on the relevance of such a model in fully developed turbulence in [1]. In this article, we focus on the particular 2 dimensional case. IDC appear as good candidates to model the statistics of natural images. They share most of their usual properties and appear to be consistent with several independent theoretical and experimental approaches of the literature. We point out the interest of IDC for applications to procedural texture synthesis.}, } @article {pmid17933706, year = {2007}, author = {Bölke, E and Peiper, M and Budach, W and Matuschek, C and Schwarz, A and Orth, K and Gripp, S}, title = {Unilateral keloid formation after bilateral breast surgery and unilateral radiation.}, journal = {European journal of medical research}, volume = {12}, number = {7}, pages = {320-322}, pmid = {17933706}, issn = {0949-2321}, mesh = {Breast Neoplasms/*therapy ; Carcinoma, Ductal, Breast/*therapy ; Female ; Humans ; Keloid/*etiology/radiotherapy/surgery ; Mastectomy, Segmental/*adverse effects ; Middle Aged ; *Postoperative Complications ; Radiotherapy, Adjuvant ; }, abstract = {BACKGROUND: Keloid is a hypertrophic scar that may arise within 6 months after injury in susceptible individuals. Different therapies like surgical excision, intralesional steroid injections, local application of pressure, or postoperative irradiation with x-rays or electrons are reported. Although an immediate starting of therapy after surgery is usually recommended, delayed radiotherapy may also be effective.

CASE REPORT: We report on a 48 year old women with a history of an invasive ductal carcinoma in the upper lateral quadrant of the left breast. A breast conserving tumor resection with axillary dissection was performed. An adapting reduction mammaplasty was carried out on the right breast for cosmetic reasons at the same time. 5 weeks after surgery, adjuvant radiotherapy was applied with a total dose of 59 Gy to the left breast. 10 weeks after surgery and by the end of radiotherapy, a keloid had developed on the right breast with reduction mammaplasty, but not on the left irradiated one. 8 months after initial surgery the patient's keloid formation on the right mamma was removed by surgical resection and a keloid prevention with postoperative radiotherapy with 20 Gy was performed.

CONCLUSION: Postoperative radiation of the scar prevented effectively keloid formation while simultaneously a hypertrophic scar developed in the non-irradiated scar.}, } @article {pmid17929165, year = {2008}, author = {Rakha, EA and El-Sayed, ME and Menon, S and Green, AR and Lee, AH and Ellis, IO}, title = {Histologic grading is an independent prognostic factor in invasive lobular carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {111}, number = {1}, pages = {121-127}, doi = {10.1007/s10549-007-9768-4}, pmid = {17929165}, issn = {0167-6806}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Prognosis ; }, abstract = {UNLABELLED: Invasive lobular carcinoma (ILC) comprises approximately 5-15% of breast cancers and appears to have a distinct biology. As it is less common than invasive ductal carcinoma, few studies of large size have addressed the value of assessment of histologic grade in ILC.

METHODS: This study is based on a large and well-characterised consecutive series of breast cancer (4,987 cases), from a single institution, with a long-term follow-up to assess the prognostic value of routine assessment of histologic grade in ILC. Histologic grade and other clinicopathological data were available in 517 pure ILC cases. A panel of biomarkers was also available for 215 cases.

RESULTS: The majority of ILC was of classical and mixed lobular variants (89%). Most ILC cases were moderately differentiated (grade 2) tumours (76%), while a small proportion of tumours were either grade 1 or 3 tumours (12% each). There were positive associations between histologic grade and other clinicopathological variables of poor prognosis such as larger size, positive lymph node, vascular invasion, oestrogen receptor and androgen receptor negativity and p53 positivity. Multivariate analyses showed that histologic grade is an independent predictor of shorter breast cancer specific survival and disease free interval.

CONCLUSION: Histologic grade of ILC, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive lobular carcinoma of the breast and should be provided routinely in pathology reports.}, } @article {pmid17927880, year = {2007}, author = {Dai, WB and Zheng, YW and Mi, XY and Liu, N and Lin, H and Yan, J}, title = {[Expression and significance of TRAF4 protein in breast carcinoma].}, journal = {Ai zheng = Aizheng = Chinese journal of cancer}, volume = {26}, number = {10}, pages = {1095-1098}, pmid = {17927880}, mesh = {Adult ; Aged ; Breast/cytology/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; TNF Receptor-Associated Factor 4/*metabolism ; }, abstract = {BACKGROUND & OBJECTIVE: The researches about the expression of tumor necrosis factor receptor-associated factor 4 (TRAF4) in breast cancer are disputable. This study was to investigate the expression of TRAF4 in normal breast, breast carcinoma tissue, and cell lines with different invasive abilities.

METHODS: The expression of TRAF4 in 70 specimens of breast carcinoma and 14 specimens of normal breast tissues was detected by SP immunohistochemistry. The expression of TRAF4 in breast cancer cell lines, MDA-MB-231 with high invasive ability and MCF-7 with low invasive ability, was detected by Western blot.

RESULTS: TRAF4 was expressed both in cell cytoplasm and nuclei in normal breast tissues. The cytoplasmic positive rates of TRAF4 were 78.57% in normal breast tissues, 88.57% in non-invasive ductal carcinoma, and 91.43% in invasive ductal carcinoma (P>0.05). The nuclear positive rate of TRAF4 was significantly higher in normal breast tissues than in non-invasive ductal carcinoma (64.28% vs. 28.57%, P<0.01), and higher in non-invasive ductal carcinoma than in invasive ductal carcinoma (28.57% vs. 5.70%, P<0.05). The protein level of TRAF4 was slightly higher in MDA-MB-231 cells than in MCF-7 cells (P>0.05).

CONCLUSION: The nuclear expression of TRAF4 in breast carcinoma is suppressed, and correlated to the invasive ability of breast cancer.}, } @article {pmid17925846, year = {2007}, author = {Clegg-Lamptey, J and Hodasi, W}, title = {A study of breast cancer in korle bu teaching hospital: assessing the impact of health education.}, journal = {Ghana medical journal}, volume = {41}, number = {2}, pages = {72-77}, pmid = {17925846}, issn = {0016-9560}, abstract = {SUMMARY INTRODUCTION: Many patients with breast cancer report late with advanced disease. It is not known if recent breast awareness education programmes have led to a change in this trend at the Korle Bu Teaching hospital (KBTH).

METHOD: A prospective study of the characteristics of breast cancer patients seen by a surgical unit at KBTH over a three year period.

RESULTS: There were 158 patients, 156 females and 2 males. The age group most commonly affected was 40-49. The upper outer quadrant of the breast was affected in 67/158 (42.4%) and all quadrants affected in 29/158 (18.4%). Ninety one (57.6%) had Stage III - IV disease and the average duration of symptoms was 10 months. Average tumour size was 6cm x 7cm. Diagnosis was by triple assessment with Fine needle aspiration cytology the most frequently used pathological investigation. Invasive ductal carcinoma was the commonest pathological type (115/134). Eighty three (52.5%) had mastectomy and 12 (7.6%) had wide local excision. Neoadjuvant chemotherapy was given to 77/123 (62.6%), 5 of whom had complete pathological response. Fifty five (34.8%) were lost to follow up: 20 before treatment commenced, 15 during or after neoadjuvant chemotherapy and 14 after treatment. Eleven developed lymphoedema. There were 42 metastatic events affecting 35 patients during follow-up, including pleura (11), brain (10) and lungs (9).

CONCLUSIONS: Breast cancer continues to affect a young population and patients still present late with advanced disease. Education needs to be intensified, but research into the reasons for late presentation will help address the reasons/misconceptions responsible for this state of affairs.}, } @article {pmid17924407, year = {2007}, author = {Garg, S and Mohan, H and Bal, A and Attri, AK and Kochhar, S}, title = {A comparative analysis of core needle biopsy and fine-needle aspiration cytology in the evaluation of palpable and mammographically detected suspicious breast lesions.}, journal = {Diagnostic cytopathology}, volume = {35}, number = {11}, pages = {681-689}, doi = {10.1002/dc.20721}, pmid = {17924407}, issn = {8755-1039}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy, Fine-Needle ; *Biopsy, Needle ; Breast/*pathology ; Breast Diseases/*pathology ; Breast Neoplasms/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {The present study was undertaken to compare the efficacy of needle core biopsy (NCB) of the breast with fine-needle aspiration cytology (FNAC) in breast lesions (palpable and non-palpable) in the Indian set-up, along with the assessment of tumor grading with both the techniques. Fifty patients with suspicious breast lesions were subjected to simultaneous FNAC and ultrasound-guided NCB following an initial mammographic evaluation. Cases were categorized into benign, benign with atypia, suspicious and malignant groups. In cases of infiltrating duct carcinomas, grading was performed on cytological smears as well as on NCB specimens. Both the techniques were compared, and findings were correlated with radiological and excision findings. Out of 50 cases, 18 were found to be benign and 32 malignant on final pathological diagnosis. Maximum number of patients with benign diagnosis was in the fourth decade (42.11%) and malignant diagnosis in the fourth as well as fifth decade (35.48% each). Sensitivity and specificity of mammography for the diagnosis of malignancy was 84.37% and 83.33%, respectively. Sensitivity and specificity of FNAC for malignant diagnosis was 78.15% and 94.44%, respectively, and of NCB was 96.5% and 100%, respectively. But NCB had a slightly higher specimen inadequacy rate (8%). NCB improved diagnostic categorization over FNAC by 18%. Tumor grading in cases of IDC showed high concordance rate between NCB and subsequent excision biopsy (94.44%) but low concordance rate between NCB and FNAC (59.1%). NCB is superior to FNAC in the diagnosis of breast lesions in terms of sensitivity, specificity, correct histological categorization of the lesions as well as tumor grading.}, } @article {pmid17923781, year = {2007}, author = {Park, MJ and Cha, ES and Kang, BJ and Ihn, YK and Baik, JH}, title = {The role of diffusion-weighted imaging and the apparent diffusion coefficient (ADC) values for breast tumors.}, journal = {Korean journal of radiology}, volume = {8}, number = {5}, pages = {390-396}, pmid = {17923781}, issn = {1229-6929}, mesh = {Adenocarcinoma, Mucinous/*diagnosis ; Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis ; Contrast Media/administration & dosage ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Imaging, Three-Dimensional/methods ; Middle Aged ; Observer Variation ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: We wanted to evaluate the role of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) for detecting breast tumors, as compared with the T1- and T2-weighted images.

MATERIALS AND METHODS: Forty-one female patients underwent breast MRI, and this included the T1-, T2-, DWI and dynamic contrast-enhanced images. Sixty-five enhancing lesions were detected on the dynamic contrast-enhanced images and we used this as a reference image for detecting tumor. Fifty-six breast lesions were detected on DWI and the histological diagnoses were as follows: 43 invasive ductal carcinomas, one mucinous carcinoma, one mixed infiltrative and mucinous carcinoma, seven ductal carcinomas in situ (DCIS), and four benign tumors. First, we compared the detectability of breast lesions on DWI with that of the T1- and T2-weighted images. We then compared the ADCs of the malignant and benign breast lesions to the ADCs of the normal fibroglandular tissue.

RESULTS: Fifty-six lesions were detected via DWI (detectability of 86.2%). The detectabilities of breast lesions on the T1- and T2-weighted imaging were 61.5% (40/65) and 75.4% (49/65), respectively. The mean ADCs of the invasive ductal carcinoma (0.89+/-0.18 x 10(-3)mm(2)/second) and DCIS (1.17+/-0.18 x 10(-3)mm(2)/ second) are significantly lower than those of the benign lesions (1.41+/-0.56 x 10(-3)mm(2)/second) and the normal fibroglandular tissue (1.51+/-0.29 x 10(-3)mm(2)/ second).

CONCLUSION: DWI has a high sensitivity for detecting breast tumors, and especially for detecting malignant breast tumors. DWI was an effective imaging technique for detecting breast lesions, as compared to using the T1- and T2-weighted images.}, } @article {pmid17923265, year = {2007}, author = {Guo, LL and Gao, P and Wu, YG and Jian, WC and Hao, CY and Li, H and Lin, XY}, title = {Alteration of cyclin D1 in Chinese patients with breast carcinoma and its correlation with Ki-67, pRb, and p53.}, journal = {Archives of medical research}, volume = {38}, number = {8}, pages = {846-852}, doi = {10.1016/j.arcmed.2007.06.004}, pmid = {17923265}, issn = {0188-4409}, mesh = {Adult ; Age Distribution ; Blotting, Southern ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; China/epidemiology ; Cyclin D1/*metabolism ; Female ; Follow-Up Studies ; Gene Amplification ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/metabolism ; Retinoblastoma Protein/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Time Factors ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: For the female population in Asia, systematic investigation on alterations of cyclin D1 in breast carcinoma is rare, and correlation between cyclin D1 expression with clinicopathological parameters, survival rate, and other prognostic marker associated with cell cycle is unclear.

METHODS: Expression of cyclin D1 protein, Ki-67, pRb, and p53 was determined by immunohistochemistry in 18 cases of early breast carcinomas and 80 cases of invasive ductal carcinomas. Genetic alteration of cyclin D1 gene and overexpression of cyclin D1 mRNA were detected by Southern blot and RT-PCR, respectively.

RESULTS: Expression of cyclin D1 is negative in usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH). However, in 52.0% (51/98) of all breast carcinomas, positive expression of cyclin D1 was observed. Five-year survival rate of the patients with positive expression of cyclin D1 (52.7%) is significantly lower than the cases with negative expression of cyclin D1 (72.1%). Positive rate of cyclin D1 protein in invasive ductal carcinoma (52.5%) is slightly higher than overexpression rate (40.8%) of cyclin D1 mRNA but significantly higher than amplification rate of cyclin D1 gene (18.4%). Expression of cyclin D1 is correlated with Ki-67 expression, but not correlated with pRb and p53 expression.

CONCLUSIONS: Positive expression of cyclin D1 could serve as a poor prognostic marker for Chinese patients with breast carcinoma independent of nodal metastasis and clinical stage. Expression of cyclin D1 protein is affected more directly by overexpression of cyclin D1 mRNA rather than cyclin D1 gene amplification. The cooperation between pRb and p53 with cyclin D1 protein in the carcinogenesis of breast carcinoma is not supported by the results.}, } @article {pmid17920374, year = {2007}, author = {Skalidis, EI and Hamilos, MI and Chlouverakis, G and Kochiadakis, GE and Parthenakis, FI and Vardas, PE}, title = {Acute effect of esmolol intravenously on coronary microcirculation in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {100}, number = {8}, pages = {1299-1302}, doi = {10.1016/j.amjcard.2007.05.055}, pmid = {17920374}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/administration & dosage/pharmacology/*therapeutic use ; Blood Flow Velocity ; Blood Pressure ; Cardiomyopathy, Dilated/diagnostic imaging/*drug therapy/*physiopathology ; Coronary Angiography ; Coronary Circulation/drug effects/*physiology ; Female ; Humans ; Infusions, Intravenous ; Laser-Doppler Flowmetry ; Male ; Middle Aged ; Propanolamines/administration & dosage/pharmacology/*therapeutic use ; Pulsatile Flow ; }, abstract = {Although coronary flow reserve (CFR) impairment was correlated with the prognosis of patients with idiopathic dilated cardiomyopathy (IDC) and microvascular ischemia was implicated in the progress of the disease, little is known about the effect of the established therapy with beta blockers on coronary microcirculation. The purpose of this study was to assess the effect of beta(1) blockade on coronary blood flow and CFR in patients with IDC. Fourteen patients with IDC and 10 control subjects underwent time-averaged peak coronary flow velocity (APCFV) measurements (centimeters per second) in the proximal left anterior descending coronary artery at baseline and at maximal hyperemia before and after beta(1) blockade with intravenous esmolol. CFR was defined as APCFV at maximal hyperemia/APCFV at baseline. Although there were no significant differences in APCFV at baseline between patients with IDC and controls, patients with IDC had significantly lower APCFV at maximal hyperemia than controls (54.2 +/- 12.0 vs 75.1 +/- 18.6, p <0.05) and decreased CFR (2.39 +/- 0.38 vs 3.50 +/- 0.54, respectively, p <0.05). After beta(1) blockade, a significant decrease in APCFV at baseline (19.5 +/- 3.7 vs 22.9 +/- 5.0, p <0.05) and enhancement of APCFV at maximal hyperemia (59.5 +/- 13.3 vs 54.2 +/- 12.0, p <0.05) were observed in patients with IDC, but not in control subjects, leading to significant improvement in CFR (3.06 +/- 0.40 vs 2.39 +/- 0.38, p <0.05). In conclusion, patients with IDC had alterations in coronary blood flow and decreased CFR that improved after beta(1) blockade. These alterations in microvascular function, which are partially reversed by beta blockade, may be 1 of the underlying mechanisms that contribute to the improved prognosis of patients with IDC under such therapy.}, } @article {pmid17914245, year = {2007}, author = {Alexe, G and Dalgin, GS and Ganesan, S and Delisi, C and Bhanot, G}, title = {Analysis of breast cancer progression using principal component analysis and clustering.}, journal = {Journal of biosciences}, volume = {32}, number = {5}, pages = {1027-1039}, pmid = {17914245}, issn = {0250-5991}, mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*metabolism/pathology ; Cluster Analysis ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Neoplasm Invasiveness/genetics ; Oligonucleotide Array Sequence Analysis ; Predictive Value of Tests ; *Principal Component Analysis ; Signal Transduction/genetics ; }, abstract = {We develop a new technique to analyse microarray data which uses a combination of principal components analysis and consensus ensemble k-clustering to find robust clusters and gene markers in the data. We apply our method to a public microarray breast cancer dataset which has expression levels of genes in normal samples as well as in three pathological stages of disease; namely, atypical ductal hyperplasia or ADH, ductal carcinoma in situ or DCIS and invasive ductal carcinoma or IDC. Our method averages over clustering techniques and data perturbation to find stable, robust clusters and gene markers. We identify the clusters and their pathways with distinct subtypes of breast cancer (Luminal,Basal and Her2+). We confirm that the cancer phenotype develops early (in early hyperplasia or ADH stage) and find from our analysis that each subtype progresses from ADH to DCIS to IDC along its own specific pathway, as if each was a distinct disease.}, } @article {pmid17914088, year = {2007}, author = {Biglia, N and Mariani, L and Sgro, L and Mininanni, P and Moggio, G and Sismondi, P}, title = {Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment.}, journal = {Endocrine-related cancer}, volume = {14}, number = {3}, pages = {549-567}, doi = {10.1677/ERC-06-0060}, pmid = {17914088}, issn = {1351-0088}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/*chemically induced/diagnosis/*epidemiology/therapy ; Carcinoma, Lobular/*chemically induced/diagnosis/*epidemiology/therapy ; Combined Modality Therapy ; Estrogen Replacement Therapy/*adverse effects ; Feasibility Studies ; Female ; Humans ; Incidence ; Intraoperative Period ; Magnetic Resonance Imaging ; Mammography ; Mastectomy, Segmental ; Mastectomy, Simple ; Neoplasm Invasiveness/diagnosis ; Prognosis ; Risk Assessment ; Sentinel Lymph Node Biopsy ; Ultrasonography, Mammary ; }, abstract = {A growing body of evidence support the association between the use of hormone replacement therapy (HRT) and a higher risk of both invasive lobular carcinoma (ILC) and invasive ductal-lobular mixed carcinoma (IDLC). Overall biological and clinical features of ILC entail a more cautious diagnostic and therapeutic approach as compared with invasive ductal carcinoma (IDC). ILCs are more frequently multifocal, multicentric and/or bilateral. Mammography and ultrasound show, therefore, significant limitations, while the higher sensitivity of magnetic resonance imaging in the detection of multifocal and/or multicentric lesions seems to improve the accuracy of preoperative staging of ILCs. Early diagnosis is even more challenging because the difficult in the localization and the sparse cellularity of lobular tumours may determine a false negative core biopsy. ILC is characterized by low proliferative activity, C-ErbB-2 negativity, bcl-2 positivity, p53 and VEGF negativity, oestrogen and progesterone positive receptors, low grade and low likelihood of lymphatic-vascular invasion. However, this more favourable biological behaviour does not reflect into a better disease-free and overall survival as compared with IDC. Since lobular histology is associated with a higher risk of positive margins, mastectomy is often preferred to breast conservative surgery. Moreover, only few patients with ILC achieve a pathologic response to preoperative chemotherapy and, therefore, in most patients mastectomy can be regarded as the safer surgical treatment. The preoperative staging and the follow-up of patients with ILC are also complicated by the particular metastatic pattern of such histotype. In fact, metastases are more frequently distributed to the gastrointestinal tract, peritoneum/retroperitoneum and gynaecological organs than in IDC.}, } @article {pmid17909406, year = {2007}, author = {Seifert, L and Chollet, D and Chatard, JC}, title = {Kinematic changes during a 100-m front crawl: effects of performance level and gender.}, journal = {Medicine and science in sports and exercise}, volume = {39}, number = {10}, pages = {1784-1793}, doi = {10.1249/mss.0b013e3180f62f38}, pmid = {17909406}, issn = {0195-9131}, mesh = {Adolescent ; Adult ; Arm ; Biomechanical Phenomena ; Competitive Behavior/*physiology ; Female ; France ; Functional Laterality/physiology ; Humans ; Leg ; Male ; Psychomotor Performance/*physiology ; Sex Factors ; Swimming/*physiology ; Task Performance and Analysis ; }, abstract = {PURPOSE: This study analyzed kinematic changes during a 100-m front crawl to investigate the effects of performance level and gender, comparing 12 high-speed males, 8 medium-speed males, 8 low-speed males, and 8 high-speed females.

METHODS: Assessments were made throughout the race in a 25-m pool divided into five zones of 5 m. Velocity (V), stroke rate (SR), and stroke length (SL) were calculated for each 25-m length (L1 to L4) and for each 5-m zone. Four stroke phases were identified by video analysis, and the index of coordination (IdC) was calculated. Three modes of arm coordination were identified: catch-up, opposition, and superposition. The leg kick was also analyzed.

RESULTS: The high-speed male swimmers were distinguished by higher V (1.89 m.s(-1)), SR (0.78 Hz), SL (2.16 m per stroke), propulsive phase (54%), and IdC (3.8%) (P < 0.05), and by the stability of these values throughout the race. The medium- and low-speed males had an opposition coordination (-1% < IdC < 1%) during the third length of the 100 m. Because of fatigue in length 4, they spent more time with the hand in the push phase (possibly because of a decrease in hand velocity) and changed to superposition coordination (medium-speed males: IdC = 2.78%; low-speed males: IdC = 1.12%) (P < 0.05). This change was ineffective, however, as SL continued to decrease throughout the 100 m (P < 0.05). The main gender findings were the greater SL of the males versus the females (1.81 m per stroke) (P < 0.05) and the similar IdC of both high-speed groups (females: 4.4%).

CONCLUSION: The high-speed swimmers were characterized by higher and more stable SL and IdC. The principal gender effect was greater SL in the males than in the females.}, } @article {pmid17905661, year = {2008}, author = {Jansen, A and Mischi, M and Bracke, F and van Dantzig, JM and Peels, K and Lamfers, E and van Hemel, N and Korsten, H}, title = {Novel ultrasound contrast agent dilution method for the assessment of ventricular ejection fraction.}, journal = {European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology}, volume = {9}, number = {4}, pages = {489-493}, doi = {10.1016/j.euje.2007.07.007}, pmid = {17905661}, issn = {1532-2114}, mesh = {Aged ; Algorithms ; *Contrast Media ; Echocardiography ; Female ; Heart Diseases/*diagnostic imaging ; Humans ; Male ; Middle Aged ; *Phospholipids ; *Stroke Volume ; *Sulfur Hexafluoride ; *Ventricular Function, Left ; }, abstract = {AIMS: Left ventricular (LV) ejection fraction is an important determinant of prognosis in heart failure. We evaluated the accuracy of a novel algorithm for LV ejection fraction quantification based on indicator dilution curve (IDC) principles using ultrasound contrast as indicator, and compared the results with contrast enhanced biplane LV ejection fraction assessment. Method A diluted ultrasound contrast bolus (SonoVue) was injected intravenously in 31 patients (19 male, age 65 +/- 11) with known or suspected heart disease. A total of 68 recordings were made. The developed algorithm used the left atrium and LV IDC for LV ejection fraction measurement. Biplane enhanced LV ejection fraction measurements with pure ultrasound contrast (SonoVue) were determined in multiple four- and two-chamber recordings as reference.

RESULTS: The mean LV ejection fraction measured by biplane and IDC method was 33 +/- 17% and 35 +/- 18%, respectively. A correlation coefficient r = 0.93 was observed between the two methods. Bland-Altman analysis demonstrated a slight LV ejection fraction overestimation with IDC (mean 1.9 +/- 6.3%).

CONCLUSION: A new fast method for LV ejection fraction assessment based on IDC principles is described and comparison with contrast enhanced biplane LV ejection fraction quantification shows accurate results.}, } @article {pmid17899367, year = {2008}, author = {Putignani, L and Raffa, S and Pescosolido, R and Aimati, L and Signore, F and Torrisi, MR and Grammatico, P}, title = {Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria.}, journal = {Breast cancer research and treatment}, volume = {110}, number = {3}, pages = {439-452}, doi = {10.1007/s10549-007-9738-x}, pmid = {17899367}, issn = {0167-6806}, mesh = {Blotting, Western ; Breast Neoplasms/*enzymology ; Female ; Fluorescent Antibody Technique ; Humans ; Microscopy, Electron, Transmission ; Microscopy, Immunoelectron ; Mitochondria/*enzymology/ultrastructure ; Multienzyme Complexes/*biosynthesis ; *Oxidative Phosphorylation ; Tumor Cells, Cultured ; }, abstract = {Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F(1)beta subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F(1)beta differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.}, } @article {pmid17899107, year = {2008}, author = {Kettritz, U}, title = {Modern concepts of ductal carcinoma in situ (DCIS) and its diagnosis through percutaneous biopsy.}, journal = {European radiology}, volume = {18}, number = {2}, pages = {343-350}, pmid = {17899107}, issn = {0938-7994}, mesh = {Biopsy/methods ; Biopsy, Needle ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Female ; Humans ; Sensitivity and Specificity ; Vacuum ; }, abstract = {The incidence of ductal breast carcinoma in situ (DCIS) is increasing and currently lies at about 15% of all breast cancers. Detection of DCIS reduces the subsequent incidence of invasive ductal carcinoma. Patients with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions are best served by minimally invasive biopsies to improve the precision of diagnosing DCIS lesions. Vacuum-assisted biopsies have the greatest sensitivity and specificity of the biopsy techniques and reduce tumor upgrading of DCIS lesions at operation by at least half compared with core-needle biopsy. Moreover, vacuum-assisted biopsies have proved to be safe and reduce health care costs. Since they provide a maximum of preoperative information, vacuum-assisted biopsies could improve outcomes in patients with DCIS.}, } @article {pmid17898060, year = {2007}, author = {Herschke, F and Plumet, S and Duhen, T and Azocar, O and Druelle, J and Laine, D and Wild, TF and Rabourdin-Combe, C and Gerlier, D and Valentin, H}, title = {Cell-cell fusion induced by measles virus amplifies the type I interferon response.}, journal = {Journal of virology}, volume = {81}, number = {23}, pages = {12859-12871}, pmid = {17898060}, issn = {1098-5514}, mesh = {Animals ; Cell Fusion ; Cell Line ; Cell Nucleus/chemistry ; Chlorocebus aethiops ; Dendritic Cells/immunology/*virology ; Epithelial Cells/immunology/*virology ; Giant Cells/cytology/immunology/*virology ; Humans ; Interferon Regulatory Factor-3/analysis ; Interferon Regulatory Factor-7/analysis ; Interferon Type I/*biosynthesis ; Measles virus/genetics/*immunology/*physiology ; Microscopy, Video ; Viral Fusion Proteins/immunology/physiology ; Viral Proteins/immunology/physiology ; }, abstract = {Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-beta) production is amplified in vitro by the formation of virus-induced MGC derived from human epithelial cells or mature conventional dendritic cells. Both fusion and IFN-beta response amplification were inhibited in a dose-dependent way by a fusion-inhibitory peptide after MeV infection of epithelial cells. This effect was observed at both low and high multiplicities of infection. While in the absence of virus replication, the cell-cell fusion mediated by MeV H/F glycoproteins did not activate any IFN-alpha/beta production, an amplified IFN-beta response was observed when H/F-induced MGC were infected with a nonfusogenic recombinant chimerical virus. Time lapse microscopy studies revealed that MeV-infected MGC from epithelial cells have a highly dynamic behavior and an unexpected long life span. Following cell-cell fusion, both of the RIG-I and IFN-beta gene deficiencies were trans complemented to induce IFN-beta production. Production of IFN-beta and IFN-alpha was also observed in MeV-infected immature dendritic cells (iDC) and mature dendritic cells (mDC). In contrast to iDC, MeV infection of mDC induced MGC, which produced enhanced amounts of IFN-alpha/beta. The amplification of IFN-beta production was associated with a sustained nuclear localization of IFN regulatory factor 3 (IRF-3) in MeV-induced MGC derived from both epithelial cells and mDC, while the IRF-7 up-regulation was poorly sensitive to the fusion process. Therefore, MeV-induced cell-cell fusion amplifies IFN-alpha/beta production in infected cells, and this indicates that MGC contribute to the antiviral immune response.}, } @article {pmid17889185, year = {2007}, author = {Agüero, J and Almenar, L and Martínez-Dolz, L and Moro, J and Izquierdo, MT and Cano, O and Salvador, A}, title = {Differences in clinical profile and survival after heart transplantation according to prior heart disease.}, journal = {Transplantation proceedings}, volume = {39}, number = {7}, pages = {2350-2352}, doi = {10.1016/j.transproceed.2007.06.068}, pmid = {17889185}, issn = {0041-1345}, mesh = {Adult ; Aged ; Analysis of Variance ; Female ; Graft Survival/*physiology ; Heart Diseases/classification/*physiopathology/*surgery ; Heart Transplantation/mortality/*physiology ; Humans ; Male ; Middle Aged ; Patient Selection ; Retrospective Studies ; Survival Analysis ; Survivors ; }, abstract = {OBJECTIVE: The objective of this study was to compare baseline characteristics and long-term survival among patients undergoing heart transplantation (HT) according to the 3 main types of prior heart disease: ischemic, idiopathic dilated cardiomyopathy (IDC), and valvular.

MATERIALS AND METHODS: Four hundred twenty-three HTs performed between 1989 and 2005 were included. We excluded pediatric transplantation, retransplantations, combined transplantations (lung and kidney), and transplantations due to heart diseases other than ischemic, IDC, and valvular. Baseline characteristics of the recipients were analyzed, as well as short-term and long- term survival by groups. Analysis of variance (ANOVA) was used for continuous variables and chi-square was used for categorical variables. Survival analysis was computed using Kaplan-Meier curves and the log-rank test, as well as multivariate analysis using logistic regression.

RESULTS: The ischemic and valvular heart disease groups were older and had a more frequent history of prior heart surgery and circulatory support at the time of transplantation compared with the IDC group. The incidence of arterial hypertension and dyslipidemia was higher among ischemic heart disease recipients. Survival rates at 30 days did not show significant differences (ischemic, 88%; IDC, 93%; and valvular; 84%; P = .21). Long-term survival rates were greater in the IDC than in the valvular or ischemic heart disease groups (75% vs 65% and 62%, respectively; P = .021). The multivariate analysis showed an association between the IDC group and long-term survival (odds ratio [OR], 0.55; 95% confidence interval [CI] 0.35-0.89; P = .015).

CONCLUSIONS: (1) Patients showed a different clinical profiles depending on their pretransplantation heart disease. (2) There were no differences in early mortality between the groups. (3) Long-term survival was significantly greater among IDC transplant recipients and similar in ischemic and valvular heart disease transplant recipients.}, } @article {pmid17885501, year = {2007}, author = {Kazakov, DV and Nemcova, J and Mikyskova, I and Belousova, IE and Vazmitel, M and Michal, M}, title = {Human papillomavirus in lesions of anogenital mammary-like glands.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {26}, number = {4}, pages = {475-480}, doi = {10.1097/pgp.0b013e31803104af}, pmid = {17885501}, issn = {0277-1691}, mesh = {Adult ; Aged ; Anus Neoplasms/*virology ; Exocrine Glands/*pathology ; Female ; Genital Neoplasms, Female/*virology ; Humans ; Male ; Middle Aged ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/*epidemiology ; Polymerase Chain Reaction ; Tumor Virus Infections/*epidemiology ; }, abstract = {Long considered as ectopic breast tissue, anogenital mammary-like glands (MLGs) have recently been suggested to represent distinctive structures located in the anogenital area. We studied 16 neoplasms of anogenital MLG for human papillomavirus (HPV) DNA using INNO-line probe assay (LiPA) HPV Genotyping kit, GP5+/6+, CP(SGB), and FAP 6085-6319 primer sets. The lesions included 3 fibroadenomas, 2 adenosis tumors, 1 invasive ductal carcinoma, 1 tubulolobular carcinoma, 2 hidradenoma papilliferum with prominent cystic change rendering a cystadenoma appearance and oxyphilic metaplasia, and 7 cases of extramammary Paget disease. All 3 fibroadenomas, both adenosis tumors, both hidradenoma papilliferum, and the tubulolobular carcinoma proved negative for HPV DNA. HPV-31 was detected by LiPA in the case of invasive ductal carcinoma. In 2 of the 7 patients with extramammary Paget disease, there was HPV DNA present in the lesional tissue, typed as HPV-6 (LiPA) and a type which was closely related to HPV-21 and HPV-24 (FAP 6085-6319), whereas the remaining 5 cases tested negative. These results coupled with those obtained from literature review suggest that HPV plays no causative role in lesions of anogenital MLG.}, } @article {pmid17883162, year = {2007}, author = {Khan, N and Rana, F and Afroz, N and Khan, MA}, title = {Cytohistomorphological grading of breast carcinoma with special reference to apoptotic rates and lymph node metastasis.}, journal = {Indian journal of pathology & microbiology}, volume = {50}, number = {3}, pages = {613-618}, pmid = {17883162}, issn = {0377-4929}, mesh = {Apoptosis ; Biopsy, Fine-Needle ; Breast Neoplasms/*diagnosis/*pathology ; Carcinoma, Ductal, Breast/*diagnosis/*pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mammary Glands, Human/pathology ; Neoplasm Staging ; }, abstract = {To analyze the significance of comparative evaluation of cytohistomorphological grading of infiltrating ductal carcinoma with specific reference to lymphnode metastasis status and apoptotic index. 50 patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were included in the study. Concordance between cytological and histological grades was calculated. Cytological smears were also evaluated for apoptotic rates and lymph node metastasis and then compared with the histological grades using regression analysis. Histological and cytological grades were comparable and statistically significant difference was found in the lymphnode metastasis rate and apoptotic index in the three cytological grades of the tumor. Moreover, by considering the apoptotic rates, the sensitivity of cytological grading significantly rose in relation to histological grade. With histological grade taken as the standard, cytology was found to be comparable but less sensitive for grading infiltrating ductal carcinoma. However, by considering lymphnode status and apoptotic rates as calculated on cytology, the sensitivity of cytological grading rose significantly in relation to histological grade. Therefore, apoptotic index incorporated with cytological grade may provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting neo-adjuvant therapy.}, } @article {pmid17879836, year = {2007}, author = {Eedarapalli, P and Biswas, N and Coleman, M}, title = {Epirubicin for breast cancer during pregnancy: a case report.}, journal = {The Journal of reproductive medicine}, volume = {52}, number = {8}, pages = {730-732}, pmid = {17879836}, issn = {0024-7758}, mesh = {Adult ; Antibiotics, Antineoplastic/*therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal/*drug therapy ; Chemotherapy, Adjuvant ; Epirubicin/*therapeutic use ; Female ; Humans ; Neoadjuvant Therapy ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy ; }, abstract = {BACKGROUND: The rarity of breast cancer in pregnancy and conflict between the optimal maternal therapy and fetal risks make its management challenging. Chemotherapy is the standard treatment for advanced cases. Epirubicin as a combination agent has been reported for breast and other cancers in pregnancy but not as a single agent. We report a case of advanced breast cancer treated with epirubicin neoadjuvant chemotherapy in pregnancy.

CASE: A 30-year-old primigravida with multifocal, grade 3 invasive ductal carcinoma, stage T2 N1M0, received 4 cycles of primary epirubicin chemotherapy in pregnancy from 23 weeks' gestation. The chemotherapy was well tolerated by the mother and fetus, and a good response was achieved prior to postnatal combination chemotherapy and definitive surgery.

CONCLUSION: Epirubicin chemotherapy appears safe and effective in pregnancy.}, } @article {pmid17867594, year = {2006}, author = {Hungermann, D and Korsching, E and Bürger, H and Röser, K and Löning, T and Herbst, H}, title = {[Salivary duct carcinomas comprise phenotypically and genotypically diverse high grade neoplasms].}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {90}, number = {}, pages = {168-176}, pmid = {17867594}, issn = {0070-4113}, mesh = {Genotype ; Humans ; Keratins/analysis ; Phenotype ; Salivary Ducts/*pathology ; Salivary Gland Neoplasms/*genetics/*pathology ; }, abstract = {Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c-erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer.}, } @article {pmid17867469, year = {2007}, author = {Pervez, S and Khan, MN and Nasir, MI}, title = {Comparative predictive value of three prognostic markers--S-phase fraction, PCNA and Mitotic count on axillary lymph node metastasis in carcinoma breast.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {19}, number = {1}, pages = {3-5}, pmid = {17867469}, issn = {1025-9589}, mesh = {Axilla/pathology ; Biomarkers ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/pathology ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; *Mitosis ; *Mitotic Index ; Neoplasm Metastasis ; Neoplasm Staging ; Pakistan ; Prognosis ; Proliferating Cell Nuclear Antigen/*analysis ; *S Phase ; }, abstract = {BACKGROUND: Axillary lymph node metastasis is the single most important prognostic factor in carcinoma of the breast. Therefore, prognostic markers that may reliably predict probability of lymph node (LN) metastases are of great value. This study was conducted to compare the predictive value of two novel prognostic / proliferative markers i.e. S-phase fraction (SPF) and proliferating cell nuclear antigen (PCNA) in parallel with mitotic index.

METHODS: Data of consecutive cases of infiltrating ductal carcinoma (IDC) breast diagnosed from July 2003 to July 2004 at the section of the Histopathology, The Aga Khan University Hospital, Karachi, were reviewed. Atotal of 112 cases of infiltrating ductal carcinoma (IDC) of the breast with axillary LN sampling were selected. SPF was calculated by flow cytometry while PCNA staining was done by immunohistochemistry. Mitotic count was calculated according to modified Bloom and Richardson's grading guidelines.

RESULT: It was observed that the number of axillary LN metastases was increased with higher SPF (p value: 0.008). However no significant difference was found between the results of various categories of PCNA on axillary LN metastases (p value: 0.182) and mitotic count with axillary lymph node metastases (p value: 0.324).

CONCLUSION: It was concluded that mitotic count and / PCNA alone cannot be used in predicting axillary LN metastases. SPF was found to be a more reliable marker compared to PCNAreactivity and conventional mitotic count in predicting axillary LN metastases.}, } @article {pmid17854427, year = {2007}, author = {Lin, A and Yan, WH and Xu, HH and Tang, LJ and Chen, XF and Zhu, M and Zhou, MY}, title = {14 bp deletion polymorphism in the HLA-G gene is a risk factor for idiopathic dilated cardiomyopathy in a Chinese Han population.}, journal = {Tissue antigens}, volume = {70}, number = {5}, pages = {427-431}, doi = {10.1111/j.1399-0039.2007.00926.x}, pmid = {17854427}, issn = {0001-2815}, mesh = {Adult ; Aged ; Asian People ; Autoimmune Diseases/*genetics ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; China ; Female ; *Genetic Predisposition to Disease ; HLA Antigens/*genetics ; HLA-G Antigens ; Histocompatibility Antigens Class I/*genetics ; Humans ; *INDEL Mutation ; Male ; Middle Aged ; Mutagenesis, Insertional ; *Polymorphism, Genetic ; Risk Factors ; Sequence Deletion ; }, abstract = {Human leukocyte antigen (HLA) has been reported to be associated with the pathogenesis of autoimmune-associated idiopathic dilated cardiomyopathy (IDC). However, the HLA-G in this context is limited. In the current study, a total of 117 IDC patients and age and sex matched 401 unrelated healthy controls in a Chinese Han population were HLA-G genotyped for the 14 bp insertion and deletion polymorphism. IDC patients showed markedly increased frequencies of -14 bp/-14 bp genotype [Pc = 0.00049, odds ratio (OR) = 2.17] and -14 bp alleles (Pc = 4.1 x 10(-5), OR = 1.97) when compared with healthy controls. Whereas the frequencies of +14 bp/+14 bp genotype (Pc = 0.0036, OR = 0.35) and +14 bp alleles (Pc = 4.1 x 10(-5), OR = 0.51) were significantly lower in IDC. These data, for the first time, indicated that 14 bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to IDC.}, } @article {pmid17851087, year = {2007}, author = {Streitner, F and Kuschyk, J and Veltmann, C and Brueckmann, M and Streitner, I and Brade, J and Neumaier, M and Bertsch, T and Schumacher, B and Borggrefe, M and Wolpert, C}, title = {Prospective study of interleukin-6 and the risk of malignant ventricular tachyarrhythmia in ICD-recipients--a pilot study.}, journal = {Cytokine}, volume = {40}, number = {1}, pages = {30-34}, doi = {10.1016/j.cyto.2007.07.187}, pmid = {17851087}, issn = {1096-0023}, mesh = {Aged ; Cardiomyopathy, Dilated/blood/complications/*therapy ; Cohort Studies ; Coronary Artery Disease/blood/complications/*therapy ; *Defibrillators, Implantable ; Female ; Follow-Up Studies ; Humans ; Interleukin-6/biosynthesis/*blood ; Male ; Pilot Projects ; Prospective Studies ; Risk Assessment ; Tachycardia, Ventricular/blood/*etiology ; Ventricular Fibrillation/blood/*etiology ; }, abstract = {OBJECTIVE: We investigated the relationship between interleukin-6 (IL-6) and the risk of experiencing spontaneous ventricular tachyarrhythmia (VT/VF) in patients with an implantable cardioverter-defibrillator (ICD).

BACKGROUND: Cytokine levels predict outcome in patients with advanced heart failure and are elevated in patients with coronary artery disease (CAD). Regarding heart rhythm disturbances, proinflammatory activity could predict the occurrence of atrial fibrillation. There is no data on cytokine levels and the risk of spontaneous VT/VF.

METHODS: IL-6 serum concentrations were determined at baseline and follow-up in 47 consecutive ICD-patients with CAD and idiopathic dilated cardiomyopathy (IDC). Data were prospectively correlated with VT/VF-incidence.

RESULTS: Thirty-six patients (76.6%) suffered from CAD and 11 (23.4%) from IDC. Mean serum concentrations of IL-6 at baseline and at 9 months follow-up were 6.12+/-4.98 and 4.63+/-6.97. 88 spontaneous VT/VF-events occurred in 13/47 patients (27.7%). Patients with VT/VF had significantly higher IL-6 levels as compared to patients without VT/VF (8.96+/-5.97 vs. 5.04+/-4.16pg/ml at baseline (p =0.03), 7.8+/-4.88 vs. 3.42+/-6.32pg/ml at follow-up (p =0.01)).

CONCLUSIONS: Elevated IL-6 serum concentrations were prospectively associated with an increased risk of spontaneous VT/VF-events in ICD-patients with CAD or IDC. These preliminary findings support a possible association of proinflammatory activity and an increased susceptibility to spontaneous VT/VF-events.}, } @article {pmid17848197, year = {2007}, author = {Zagouri, F and Sergentanis, TN and Koulocheri, D and Nonni, A and Bousiotou, A and Domeyer, P and Michalopoulos, NV and Dardamanis, D and Konstadoulakis, MM and Zografos, GC}, title = {Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report.}, journal = {World journal of surgical oncology}, volume = {5}, number = {}, pages = {101}, pmid = {17848197}, issn = {1477-7819}, mesh = {Biopsy, Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/pathology/*secondary/therapy ; Carcinoma, Lobular/pathology/*secondary/therapy ; Chemotherapy, Adjuvant ; Cholecystectomy/methods ; Female ; Follow-Up Studies ; Gallbladder Neoplasms/pathology/*secondary/surgery ; Humans ; Immunohistochemistry ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary/*pathology/therapy ; Radiotherapy, Adjuvant ; Risk Assessment ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.

CASE PRESENTATION: A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.

CONCLUSION: This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.}, } @article {pmid17826642, year = {2007}, author = {Sarzani, R and Forleo, C and Pietrucci, F and Capestro, A and Soura, E and Guida, P and Sorrentino, S and Iacoviello, M and Romito, R and Dessì-Fulgheri, P and Pitzalis, M and Rappelli, A}, title = {The 212A variant of the APJ receptor gene for the endogenous inotrope apelin is associated with slower heart failure progression in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {13}, number = {7}, pages = {521-529}, doi = {10.1016/j.cardfail.2007.04.002}, pmid = {17826642}, issn = {1532-8414}, mesh = {Adenine ; Adult ; Alleles ; Apelin ; Apelin Receptors ; Cardiomyopathy, Dilated/genetics/*physiopathology ; Cytosine ; DNA Mutational Analysis ; Disease Progression ; Female ; Follow-Up Studies ; Gene Dosage ; *Genetic Variation ; Genotype ; Guanine ; Haplotypes ; Homozygote ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Linkage Disequilibrium ; Male ; Middle Aged ; Myocardial Contraction ; Polymorphism, Genetic ; Prognosis ; Prospective Studies ; Receptors, G-Protein-Coupled/*genetics ; }, abstract = {BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) has multiple genetic and acquired causes. Apelin is an endogenous peptide that increases cardiac inotropism through his APJ receptor. No data are available concerning the APJ gene mutations responsible for IDC or on the role of APJ receptor gene variants in predicting heart failure (HF) progression.

METHODS AND RESULTS: We prospectively evaluated 202 consecutive patients with IDC and 202 matched controls: 90 were screened for APJ gene mutations and all 202 were genotyped for G212A and A445C APJ receptor polymorphisms. No mutations were found within the coding or untranslated regions of the APJ receptor, and no differences in allelic or genotype frequencies were observed comparing patients with a healthy control population. The correlations between APJ receptor polymorphisms and HF progression were assessed. During a median follow-up of 37 months, 35 patients experienced HF progression. Univariate analysis showed that patients carrying at least 1 copy of 212A had a significantly lower risk for HF-related events than those who were homozygous for the G212 variant, and multivariate analysis confirmed that it was significantly related to a more favorable prognosis.

CONCLUSIONS: APJ is unlikely to be a gene causing IDC, but the independent correlation between the 212A allele and a better prognosis suggests that it might act as a modifier gene.}, } @article {pmid17826073, year = {2007}, author = {Vo, T and Xing, Y and Meric-Bernstam, F and Mirza, N and Vlastos, G and Symmans, WF and Perkins, GH and Buchholz, TA and Babiera, GV and Kuerer, HM and Bedrosian, I and Akins, JS and Hunt, KK}, title = {Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy.}, journal = {American journal of surgery}, volume = {194}, number = {4}, pages = {527-531}, doi = {10.1016/j.amjsurg.2007.06.012}, pmid = {17826073}, issn = {1879-1883}, mesh = {Adenocarcinoma/*surgery ; Adenocarcinoma, Mucinous/*surgery ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma.

METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS).

RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology.

CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.}, } @article {pmid17826055, year = {2007}, author = {Benitez, PR and Keisch, ME and Vicini, F and Stolier, A and Scroggins, T and Walker, A and White, J and Hedberg, P and Hebert, M and Arthur, D and Zannis, V and Quiet, C and Streeter, O and Silverstein, M}, title = {Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer.}, journal = {American journal of surgery}, volume = {194}, number = {4}, pages = {456-462}, doi = {10.1016/j.amjsurg.2007.06.010}, pmid = {17826055}, issn = {1879-1883}, mesh = {Adult ; *Brachytherapy/instrumentation ; Breast Neoplasms/*pathology/*radiotherapy ; Carcinoma, Ductal, Breast/*pathology/*radiotherapy ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Time Factors ; }, abstract = {OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients.

METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted.

RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed.

CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.}, } @article {pmid17826054, year = {2007}, author = {Boughey, JC and Middleton, LP and Harker, L and Garrett, B and Fornage, B and Hunt, KK and Babiera, GV and Dempsey, P and Bedrosian, I}, title = {Utility of ultrasound and fine-needle aspiration biopsy of the axilla in the assessment of invasive lobular carcinoma of the breast.}, journal = {American journal of surgery}, volume = {194}, number = {4}, pages = {450-455}, doi = {10.1016/j.amjsurg.2007.06.017}, pmid = {17826054}, issn = {1879-1883}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; *Biopsy, Fine-Needle ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Lobular/*diagnostic imaging/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Reproducibility of Results ; Retrospective Studies ; Ultrasonography ; }, abstract = {BACKGROUND: The unique growth pattern of invasive lobular carcinoma (ILC) poses a challenge for preoperative assessment of disease extent within the breast. Whether it similarly limits lymph node staging by ultrasound (US) and fine-needle aspiration (FNA) biopsy was the subject of the current study.

METHODS: A total of 217 patients with ILC who underwent axillary US were reviewed. FNA biopsy was performed when US findings were suspicious or indeterminate. Findings were compared to literature reports of US in invasive ductal carcinoma (IDC) patients.

RESULTS: Axillary US was negative in 137 patients (63%) and suspicious or indeterminate in 80 patients (37%). FNA biopsy was positive in 62% (47/76 patients). Preoperative US and FNA biopsy identified 43 of 111 (39%) node-positive patients. Sensitivity of US with FNA biopsy correlated with primary tumor and nodal metastasis size. Similar results were seen in IDC populations.

CONCLUSION: US with FNA biopsy appears to be similarly useful in axillary staging of ILC and IDC patients.}, } @article {pmid17825955, year = {2008}, author = {Vinodkumar, R and Vaidya, SD and Siva Kumar, BV and Bhise, UN and Bhirud, SB and Mashelkar, UC}, title = {Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(4-phenylethynyl-phenyl)-1H-benzimidazoles and N-substituted 2[4-(4,4-dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1H-benzimidazoles.}, journal = {European journal of medicinal chemistry}, volume = {43}, number = {5}, pages = {986-995}, doi = {10.1016/j.ejmech.2007.06.013}, pmid = {17825955}, issn = {0223-5234}, mesh = {Alkynes/*chemical synthesis/chemistry/pharmacology ; Anti-Asthmatic Agents/*chemical synthesis/chemistry/pharmacology ; Anti-Bacterial Agents/*chemical synthesis/chemistry/pharmacology ; Benzimidazoles/*chemical synthesis/chemistry/pharmacology ; Dipeptidyl-Peptidase IV Inhibitors ; Heterocyclic Compounds, 2-Ring/*chemical synthesis/chemistry/pharmacology ; Humans ; Hypoglycemic Agents/*chemical synthesis/chemistry/pharmacology ; Phosphodiesterase 4 Inhibitors ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors ; Structure-Activity Relationship ; }, abstract = {Synthesis of a series of novel and functionalized benzimidazole derivatives by the condensation of OPDA with 4-bromobenzoic acid and subsequent reactions of the product obtained with phenylacetylene and 6-ethynyl-4,4-dimethylthiochroman utilising Sonogashira coupling has been reported. The Sonogashira coupling products were then alkylated at the benzimidazole -NH with different electrophilic reagents leading to functionalized derivatives. All the compounds synthesized were screened for their potential anti-bacterial, anti-asthmatic and anti-diabetic properties, which exhibited moderate activities in screening studies in vitro.}, } @article {pmid17823891, year = {2007}, author = {Laudanski, K and De, A and Miller-Graziano, C}, title = {Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells.}, journal = {European journal of immunology}, volume = {37}, number = {10}, pages = {2812-2824}, doi = {10.1002/eji.200636993}, pmid = {17823891}, issn = {0014-2980}, support = {GM36214/GM/NIGMS NIH HHS/United States ; GM65237/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/immunology/*physiology ; Cells, Cultured ; Dendritic Cells/*cytology/immunology ; Growth Inhibitors/*pharmacology ; HSP27 Heat-Shock Proteins ; Heat-Shock Proteins/*pharmacology ; Humans ; Macrophages/cytology/immunology ; Molecular Chaperones ; Monocytes/*cytology/immunology ; Neoplasm Proteins/*pharmacology ; Rabbits ; Receptors, Immunologic/antagonists & inhibitors/biosynthesis ; Signal Transduction/immunology ; }, abstract = {Circulating heat shock protein (HSP)-27 is associated with tumor progression and increased post-injury infection. Extracellular HSP-27 might alter monocyte (MO)-derived DC and/or MPhi function to mediate immunosuppression. HSP-27 treatment inhibited expression of CD1a and CD1b/c, antigen uptake, and allogeneic T cell induction (MLR) by IL-4 + GM-CSF-differentiated human DC while increasing some MPhi characteristics (upward arrowCD14, upward arrowCD16, upward arrowCD163). MO cytokine receptor profiles elicited by 24-h exogenous HSP-27 treatment remained supportive of immature DC (iDC) emergence (upward arrowIL-4R, downward arrowIL-6R, downward arrowM-CSFR). IL-10, IL-6, and M-CSF (which promote MPhi differentiation) were significantly increased in IL-4 + GM-CSF + HSP-27 MO-->iDC differentiation cultures. However, HSP-27 treatment during MO differentiation to DC increased programmed cell death ligand 1 coinhibitor and depressed CD86 costimulator expression in parallel to decreased iDC MLR activity. This suggested that increased MPhi differentiation was not solely responsible for HSP-27 reduction of differentiating DC activity. HSP-27 treatment actually depressed the phagocytic capacity of MO differentiated to MPhi by IL-10 or M-CSF culture. CD163 (hemoglobin receptor) expression was depressed on M-CSF + HSP-27 MO-derived MPhi. HSP-27-mediated inhibition of MO-->iDC differentiation was reversed by p38alpha & beta inhibitor (SB202190) addition or TLR4 receptor modulation. HSP-27 impaired appropriate MO-->iDC and MO-->MPhi differentiation modulating expression of receptors necessary for their proper functions. This suggests that endogenous HSP-27 has immunoregulatory activities which could contribute to immunopathology.}, } @article {pmid17822781, year = {2007}, author = {Cirone, M and Lucania, G and Bergamo, P and Trivedi, P and Frati, L and Faggioni, A}, title = {Human herpesvirus 8 (HHV-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activity.}, journal = {Immunology letters}, volume = {113}, number = {1}, pages = {40-46}, doi = {10.1016/j.imlet.2007.07.013}, pmid = {17822781}, issn = {0165-2478}, mesh = {Cell Differentiation/*immunology ; Cells, Cultured ; Dendritic Cells/cytology/*immunology/*virology ; Herpesvirus 8, Human/*immunology ; Humans ; *Immunosuppression Therapy ; Lymphocyte Activation/*immunology ; Monocytes/cytology/*immunology/*virology ; Stem Cells/cytology/immunology/virology ; Virus Activation/immunology ; }, abstract = {Several viruses interfere with the host immune response by infecting dendritic cells and by altering their functional activity. Here, we report that exposure to Human herpesvirus 8 (HHV-8) of human dendritic cell (DC) monocyte precursors resulted in impaired immature DC (iDC) formation as indicated by a reduced CD1a expression. In accordance, the immunostimulatory ability of such iDC was significantly reduced, as indicated by mixed lymphocyte culture (MLR) assays. The immunostimulatory functions of DCs were similarly inhibited by the UV inactivated viral stocks, suggesting that the virus binding is sufficient to determine the observed effect. Furthermore, HHV8 mediated inhibition of the DC allostimulatory function was present in lipopolysaccharide (LPS) matured DCs. A strong reduction of the expression of the costimulatory molecule CD80 on the surface of the virus-exposed cells was observed as well. Impairment of dendritic cell development and function might represent an important strategy used by HHV-8 to escape from the host defense mechanisms.}, } @article {pmid17821836, year = {2007}, author = {Turashvili, G and Bouchalova, K and Bouchal, J and Kolar, Z}, title = {Expression of E-cadherin and c-erbB-2/HER-2/neu oncoprotein in high-grade breast cancer.}, journal = {Ceskoslovenska patologie}, volume = {43}, number = {3}, pages = {87-92}, pmid = {17821836}, issn = {1210-7875}, mesh = {Axilla ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Lobular/*metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.}, } @article {pmid19190693, year = {2007}, author = {Shamloula, MM and El-Shorbagy, SH and Saied, EM}, title = {P63 and cytokeratin8/18 expression in breast, atypical ductal hyperplasia, ductal carcinoma in situ and invasive duct carcinoma.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {19}, number = {3}, pages = {202-210}, pmid = {19190693}, issn = {1110-0362}, abstract = {Background and Purpose : The pattern and distribution of p63 expression as a myoepithelial/basal stem cell marker can be different between atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and may denote basal phenotype of breast ductal carcinoma. CK8/18 is a luminal marker and may indicate a luminal phenotype of IDC and its expression in ADH and DCIS may refer to a possible precursor lesion to IDC. This work was designed to study and compare the expression of p63 and cytokeratin 8/18 (CK8/18) in some cases of ADH, DCIS and IDC. Materials and Methods : Histopathological evaluation and immunohistochemical study of anti-p63 and anti- CK8/18 was performed on selected archival cases of 7 ADH, 12 DCIS, 30 IDC of known clinicopathological data and previous estrogen receptor status (ER) for IDC. Confirmatory anti-smooth muscle actin (ASMA) expression for positive p63 cases was performed. Results : p63 was expressed in the peripheral rim of the myoepithelial cell layer in ADH and DCIS with occasional gabs in DCIS. It was positive and stained occasional malignant cells in 3/30 (10%) of IDC cases. Confirmatory ASMA staining decorated the same peripheral rim of cells in ADH and DCIS, but was negative in p63 positive IDC cases. CK8/18 was positive in 100% of ADH, 8/12 (66.7%) of DCIS and 22/30 (73%) of IDC cases. Combined p63 and CK8/18 expression was noticed in 3/30 (10%) of IDC. Conclusion : It is concluded from this study that p63 is specific and valuable in differentiating myoepithelial cells and is more specific and valuable than other myoepithelial markers, as ASMA and can differentiate between ADH, DCIS, IDC as it stains peripheral myoepithelial cells in ADH and DCIS with gabs in the latter and does not stain any neoplastic cells. In IDC, it is positive in malignant cells in a minority of cases which may indicate basal/stem cell/myoepithelial cell origin of breast carcinoma. Comparatively, CK8/18 cannot differentiate ADH, DCIS and IDC as there is no difference in its staining pattern among them, which may suggest that they are a continuum or that ADH and DCIS are precursors for the luminal phenotype of IDC. Key Words : p63 -CK8/18 -IDC -ADH -DCIS -Basal/ stem cells.}, } @article {pmid17762443, year = {2007}, author = {Papantoniou, V and Tsiouris, S and Sotiropoulou, M and Valsamaki, P and Koutsikos, J and Ptohis, N and Dimitrakakis, C and Sotiropoulou, E and Melissinou, M and Nakopoulou, L and Antsaklis, A and Zerva, C}, title = {The potential role of Calcitonin Gene-Related Peptide (CGRP) in breast carcinogenesis and its correlation with 99mTc-(V)DMSA scintimammography.}, journal = {American journal of clinical oncology}, volume = {30}, number = {4}, pages = {420-427}, doi = {10.1097/COC.0b013e3180337792}, pmid = {17762443}, issn = {1537-453X}, mesh = {Breast Neoplasms/*diagnostic imaging/metabolism ; Calcitonin Gene-Related Peptide/*metabolism ; Carcinoma, Ductal, Breast/*diagnostic imaging/metabolism ; Carcinoma, Lobular/*diagnostic imaging/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Mammography/*methods ; Pilot Projects ; Prognosis ; Radionuclide Imaging ; *Radiopharmaceuticals ; Retrospective Studies ; Sensitivity and Specificity ; *Technetium Tc 99m Dimercaptosuccinic Acid ; }, abstract = {OBJECTIVES: Experimental data suggest a role for calcitonin gene-related peptide (CGRP) in normal breast development and angiogenesis. This pilot study correlated CGRP with neoangiogenesis and the uptake of the tumor-seeking, proliferation-imaging radiotracer pentavalent technetium-99m dimercaptosuccinate (99mTc-(V)DMSA) in invasive and preinvesive breast lesions.

METHODS: Among women evaluated preoperatively by 99mTc-(V)DMSA scintimammography, 29 invasive ductal carcinomas (IDCs) were retrospectively studied: 15 isolated (Group I); 14 mixed with preinvasive pathologies (ductal carcinoma in situ [DCIS] and/or epithelial hyperplasia [EH]; Group M). CGRP staining and neoangiogenesis were compared between invasive and DCIS/EH regions and were correlated. 99mTc-(V)DMSA displayed a diffusely increased uptake pattern corresponding to DCIS/EH; its lesion-to-background (L/B) ratio was compared between images acquired at 10 and 60 minutes and its retention ratio (RR) was correlated with CGRP.

RESULTS: Seven of 15 group I and 10 of 14 group M patients (58.6% of the population) were CGRP-positive. CGRP was prevalent in the DCIS/EH component of mixed-lesions (even in the surrounding normal epithelium of nearly half), with declining intensity as advancing from DCIS/EH to high-grade IDC. Similarly, neoangiogenesis was considerably higher in DCIS/EH than in group I pure IDCs. A significant CGRP-neoangiogenesis correlation was verified only in group I. The diffuse 99mTc-(V)DMSA uptake exhibited significant, time-related L/B increase and a RR positively correlating with CGRP.

CONCLUSIONS: CGRP expression and neoangiogenesis are intensified in mixed invasive-preinvasive breast lesions; an underlying relation may exist, requiring further investigation. CGRP also appears associated with 99mTc-(V)DMSA's propensity to depict preinvasive pathologies. This relationship could denote an additional proliferative role for CGRP.}, } @article {pmid17760669, year = {2007}, author = {Jayasinghe, UW and Bilous, AM and Boyages, J}, title = {Is survival from infiltrating lobular carcinoma of the breast different from that of infiltrating ductal carcinoma?.}, journal = {The breast journal}, volume = {13}, number = {5}, pages = {479-485}, doi = {10.1111/j.1524-4741.2007.00468.x}, pmid = {17760669}, issn = {1075-122X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality/pathology ; Carcinoma, Lobular/*mortality/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Survival Rate ; }, abstract = {Previous studies of patients with breast cancer have compared survival of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) with contradictory results. This study examines the effect of the diagnosis of IDC or ILC in conjunction with age at diagnosis, pathologic tumor size, pathologic stage, histologic grade, and lymph node status of 307 women with IDC or ILC in 1992 in the Greater Western region of Sydney in Australia. Survival analysis was conducted using the Kaplan-Meier method. Relative risks associated with IDC or ILC and other important prognostic factors and adjusted for each other were computed using Cox proportional hazard regression. The proportion of grade I tumors was significantly higher in ILC (41%) than in IDC (16%). Conversely, the proportion of grade III tumors was only 18% in ILC as against 41% in IDC (p = 0.020). The 10-year survival of women with IDC was 69%, compared to 84% for ILC (p = 0.073). However, the 15 percentile point difference between overall survival of IDC and ILC was markedly reduced after adjustment for nodal status. The difference was eight percentile points for node-negative patients (p = 0.361) and five percentile points for node-positive patients (p = 0.464). Age at diagnosis, tumor size, pathologic stage, and lymph node status were independent prognostic indicators for 10-year survival. There was no prognostic difference between IDC and ILC. The result shows the importance of adjusting for other important clinicopathologic characteristics before comparing the overall survival of IDC and ILC.}, } @article {pmid17721274, year = {2007}, author = {Jang, KT and Lee, KT and Lee, JG and Choi, SH and Heo, JS and Choi, DW and Ahn, G}, title = {Immunohistochemical expression of Sonic hedgehog in intraductal papillary mucinous tumor of the pancreas.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {15}, number = {3}, pages = {294-298}, doi = {10.1097/01.pai.0000213132.71041.da}, pmid = {17721274}, issn = {1541-2016}, mesh = {Adenocarcinoma, Mucinous/chemistry/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/metabolism/*pathology ; Carcinoma, Papillary/chemistry/metabolism/*pathology ; Female ; Hedgehog Proteins/analysis/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Neoplasm Invasiveness ; Pancreatic Neoplasms/chemistry/metabolism/*pathology ; Survival Analysis ; }, abstract = {Aberrant expression of Sonic hedgehog (Shh) has been reported in many human cancers including ductal carcinoma of the pancreas. The intraductal papillary mucinous tumor (IPMT) has been considered as one of the precursor lesions of invasive ductal carcinoma of the pancreas. Shh expression in pancreatic IPMT has not been reported. We investigated an immunohistochemical (IHC) expression of Shh in 55 cases of pancreatic IPMT. We analyzed the IHC expression of Shh in the following histologic grades of tumor: adenoma (AD), moderate dysplasia (MD), noninvasive carcinoma (NIC), and invasive carcinoma (IC), and with the following histologic subtype classification: intestinal, pancreatobiliary, null, and unclassifiable type. IHC Shh expression was noted in 6 (46.2%) of 13 AD, 5 (35.7%) of 14 MD, 12 (80%) of 15 NIC, and 11 (84.6%) of 13 IC. Shh expression was significantly increased in malignant IPMT (NIC+IC) compared with nonmalignant IPMT (AD+MD) (82.1% vs. 40.7%, P=0.0005). IHC Shh expression was found in 11 (68.8%) of 16 intestinal types, 13 (92.8%) of 14 pancreatobiliary types, 8 (38.1%) of 21 null types, and 2 (50%) of 4 unclassifiable types. Intestinal and pancreatobiliary subtypes showed a high expression of Shh compared with the null and unclassifiable type of IPMT. All 3 cases of node metastasis showed IHC Shh expression in tumor cells of metastatic lymph nodes. Therefore, Shh expression may have a critical role in the late stage of carcinogenesis of IPMT, and may impact metastatic progression to the lymph nodes in malignant IPMT.}, } @article {pmid17711977, year = {2007}, author = {Cools, N and Ponsaerts, P and Van Tendeloo, VF and Berneman, ZN}, title = {Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells.}, journal = {Journal of leukocyte biology}, volume = {82}, number = {6}, pages = {1365-1374}, doi = {10.1189/jlb.0307166}, pmid = {17711977}, issn = {0741-5400}, mesh = {Animals ; Cell Differentiation ; Cell- and Tissue-Based Therapy ; Dendritic Cells/cytology/*immunology ; Humans ; Immune Tolerance/*immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Dendritic cells (DC), professional antigen-presenting cells of the immune system, exert important functions both in induction of T cell immunity, as well as tolerance. It is well established that the main function of immature DC (iDC) in their in vivo steady-state condition is to maintain peripheral tolerance to self-antigens and that these iDC mature upon encounter of so-called danger signals and subsequently promote T cell immunity. Previously, it was believed that T cell unresponsiveness induced after stimulation with iDC is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. Moreover, several reports indicate that traditional DC maturation can no longer be used to distinguish tolerogenic and immunogenic properties of DC. This review will focus on the complementary role of dendritic cells in inducing both tolerance and immunity, and we will discuss the clinical implications for dendritic cell-based therapies.}, } @article {pmid17703906, year = {2008}, author = {Kang, SS and Ko, EY and Han, BK and Shin, JH}, title = {Breast US in patients who had microcalcifications with low concern of malignancy on screening mammography.}, journal = {European journal of radiology}, volume = {67}, number = {2}, pages = {285-291}, doi = {10.1016/j.ejrad.2007.06.018}, pmid = {17703906}, issn = {0720-048X}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging ; Calcinosis/*diagnostic imaging ; Chi-Square Distribution ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Mammography ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; *Ultrasonography, Mammary ; }, abstract = {PURPOSE: To review ultrasound (US) findings in patients who have suspicious microcalcifications with low concern of malignancy (BI-RADS category 4A) on screening mammography and to evaluate helpful findings in differentiating benign and malignant lesions.

MATERIALS AND METHODS: Between August 2005 and July 2006, 192 patients showed microcalcifications only, without mass or associated density, on screening mammography. Among them, we selected 82 patients who had microcalcifications with low concern of malignancy (category 4A) that were pathologically confirmed by surgical excision after wire localization (n=23) or biopsy (n=59). Breast US was performed in 37/82 cases and we analyzed the US findings for the calcification areas in these patients, evaluating the findings with benign or malignant pathological results. We correlated US findings with mammographic calcifications using mammography-guided 2D-localization for the calcifications before US examination.

RESULTS: There were 12 malignant lesions (32.4%) including 3 invasive ductal carcinomas (IDC), one microinvasive ductal carcinoma (MIDC), 8 ductal carcinoma in situ (DCIS) and 25 benign lesions (67.6%) including 2 atypical ductal hyperplasias (ADH). IDC showed calcifications within heterogeneous hypoechoic parenchyma or calcifications within complex hypoechoic masses of taller-than-wide shape on US. One MIDC showed calcifications within heterogeneous hypoechoic parenchyma and six DCIS showed negative findings, or calcifications with a small nodule, or only calcifications on US. The most common positive US finding in benign lesions was cysts with calcifications. In 24/37 cases (64.8%) with negative US findings, 18 (75%) were benign lesions and 6 (25%) were DCIS.

CONCLUSION: In patients with category 4A microcalcifications without associated findings on screening mammography, negative US findings had a high rate of benign results (18/24, 75%). Visible calcifications within heterogeneous hypoechoic parenchyma or mass on US increased the probability of malignancy.}, } @article {pmid17703080, year = {2007}, author = {Hisa, T and Suda, K and Nobukawa, B and Ohkubo, H and Shiozawa, S and Ishigame, H and Yamao, K and Yatabe, Y}, title = {Distribution of intraductal lesions in small invasive ductal carcinoma of the pancreas.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {7}, number = {4}, pages = {341-346}, doi = {10.1159/000107268}, pmid = {17703080}, issn = {1424-3911}, mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*pathology ; }, abstract = {AIMS: To investigate the distribution of intraductal lesions in small invasive ductal carcinoma (IDC) of the pancreas.

METHODS: In 21 cases with IDCs microscopically < or = 20 mm in diameter, the intraductal lesions around a mass were studied histologically and mapped according to the pancreatic intraepithelial neoplasia (PanIN) classification.

RESULTS: PanIN-3, PanIN-2, PanIN-1B and PanIN-1A were found in 17, 10, 20 and 21 of 21 cases, respectively, and were divided into lesions in adjacent and distal areas, respectively defined as within and beyond 10 mm from the mass as follows: 100% (17/17), 100% (10/10), 95.0% (19/20) and 90.5% (19/21) in the former, while 23.5% (4/17), 50.0% (5/10), 90.0% (18/20) and 95.2% (20/21) in the latter. PanIN-3 lesions were predominantly found in the area adjacent to the mass. In some cases, significant PanIN-3 appeared to show a consecutive geographic extension around the mass via the main pancreatic duct (MPD). The distance of PanIN-3 spread was within 25 (mean 10.5) mm from the mass edge. PanIN-2 lesions were found in the area adjacent to the mass and discontinuous with the mass or PanIN-3 lesions. PanIN-1B and PanIN-1A tended mainly to exist sporadically throughout the entire pancreas. In the MPD, PanIN-3 was found in 14 (82.4%) of 17 cases and in 36 (32.1%) of 112 lesions, which was most frequent in intraductal lesions.

CONCLUSIONS: PanIN-3 lesions might be an intraductal extension of the main tumor. The resection margin of 25 mm, at least longer than 11 mm, from the mass edge will be necessary.}, } @article {pmid17690565, year = {2007}, author = {Connolly, N and Riddler, S and Stanson, J and Gooding, W and Rinaldo, CR and Ferrone, S and Whiteside, TL}, title = {Levels of antigen processing machinery components in dendritic cells generated for vaccination of HIV-1+ subjects.}, journal = {AIDS (London, England)}, volume = {21}, number = {13}, pages = {1683-1692}, doi = {10.1097/QAD.0b013e32825eabbc}, pmid = {17690565}, issn = {0269-9370}, support = {UL1 TR000005/TR/NCATS NIH HHS/United States ; R01 CA 110249/CA/NCI NIH HHS/United States ; P01 AI 55794/AI/NIAID NIH HHS/United States ; R01 CA 67108/CA/NCI NIH HHS/United States ; P01 DE 12321/DE/NIDCR NIH HHS/United States ; R01 CA 113861/CA/NCI NIH HHS/United States ; }, mesh = {AIDS Vaccines/*immunology ; Adult ; Antigen Presentation/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation/immunology ; Dendritic Cells/*immunology ; Epitopes, T-Lymphocyte/immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; HLA-A2 Antigen/analysis ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-12/biosynthesis ; Middle Aged ; Monocytes/immunology ; Vaccination ; }, abstract = {OBJECTIVE: To evaluate expression of the antigen processing machinery (APM) components and HLA molecules by monocyte-derived dendritic cells (DC) generated from chronically HIV-1 infected subjects on antiretroviral therapy (ART) and to assess their ability to ex vivo induce HIV-1 specific T cells.

METHODS: DC generated in 16 HLA-A2 positive patients were matured in cytokines, pulsed with HIV-1 or other viral peptides and tested in interferon (IFN)-gamma ELISPOT assays. Immature (i)DC, mature (m)DC and viral peptide-pulsed DC were studied by multiparameter quantitative flow cytometry for intracellular APM component expression and for HLA class I and II, beta-2 microglobulin and co-stimulatory molecule surface expression. DC from 13 normal donors served as controls.

RESULTS: Marked heterogeneity in APM component expression levels in iDC and mDC from HIV-1 positive subjects was observed. Nevertheless, the median levels were comparable to those in iDC and mDC, respectively, from normal donors. Patients' mDC pulsed with the HIV-1, influenza A, cytomegalovirus (CMV) or Epstein-Barr virus peptides induced IFN-gamma production by T cells specific for these peptides in ELISPOT assays. The frequency of T cells responsive to influenza A, cytomegalovirus or Epstein-Barr virus peptides was comparable in the patients and normal donors.

CONCLUSIONS: The APM component expression profiles of iDC and mDC were more heterogeneous in subjects with chronic HIV-1 infection on ART, than those in normal donors, although not statistically different. Ex vivo, patients' DC pulsed with HIV-1 peptides induced IFN-gamma production from autologous T cells. Thus, DC obtained from HIV-1 infected subjects on ART were phenotypically and functionally competent.}, } @article {pmid17690514, year = {2007}, author = {Sugie, T and Takeuchi, E and Kunishima, F and Yotsumoto, F and Kono, Y}, title = {A case of ductal carcinoma with squamous differentiation in malignant phyllodes tumor.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {327-332}, doi = {10.2325/jbcs.14.327}, pmid = {17690514}, issn = {1340-6868}, mesh = {Breast Neoplasms/*diagnosis/diagnostic imaging/pathology/therapy ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/pathology/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Fatal Outcome ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis/diagnostic imaging/pathology/therapy ; Phyllodes Tumor/*diagnosis/diagnostic imaging/pathology/therapy ; Radiography ; Ultrasonography ; }, abstract = {Carcinoma derived from the lining epithelial cells in malignant phyllodes tumor is a rare neoplasm of the breast and belongs to the category of carcinosarcoma. We report a case of ductal carcinoma with squamous differentiation arising in malignant phyllodes tumor. A 54-year-old woman was admitted with a rapidly enlarging left breast mass. A breast tumor with a diameter of 6 cm was located mainly in the left outer area of the breast. Mammography revealed a high-density mass with an irregular margin and ultrasound showed a cystic tumor. A pathological diagnosis of ductal carcinoma with squamous differentiation was made by fine needle aspiration and a core needle biopsy. She underwent neoadjuvant chemotherapy followed by a modified radical mastectomy with a skin flap. Histopathological examination revealed that the invasive ductal carcinoma with squamous differentiation originated from the lining epithelial cells in malignant phyllodes tumor and that there was no transition area between the carcinomatous and the sarcomatous component. She experienced lung and facial bone metastases, microscopic features of which were consistent with the sarcomatous component of the original breast carcinosarcoma. This is an extremely rare case of carcinosarcoma and the histopathological findings and review of the literature are discussed.}, } @article {pmid17690509, year = {2007}, author = {Sato, T and Muto, I and Hasegawa, M and Aono, T and Okada, T and Tamura, T and Sakai, T}, title = {A rare case of invasive ductal carcinoma with hyperprolactinemia.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {302-306}, doi = {10.2325/jbcs.14.302}, pmid = {17690509}, issn = {1340-6868}, mesh = {Adult ; Breast Neoplasms/complications/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperprolactinemia/*etiology ; Magnetic Resonance Imaging ; Mammography ; Nipples/*pathology ; Ultrasonography ; }, abstract = {We report here a rare form of invasive ductal carcinoma composed of a mass protruding from the tip of the nipple in a 43-year-old woman with hyperprolactinemia. She had been amenorrheic for 15 years following an incomplete pituitary adenomectomy for prolactinoma. She presented with a mass on the left nipple that had been growing for 6 months. Morphologically, the mass resembled adenoma of the nipple. Another mass was located in the subareolar region. She underwent mastectomy after invasive ductal carcinoma was diagnosed. Histopathologically, the tumor of the nipple was invasive ductal carcinoma, which had extended intraductally from another invasive ductal carcinoma in the subareolar region, and had infiltrated the epidermis of the nipple (Paget's disease). MR mammography successfully detected the relationship between the tumors. Postoperatively, the plasma prolactin level was abnormally high, while the plasma estradiol level was quite low, although macro-pituitary adenoma was not detected by MRI. The patient was treated with bromocriptine mesilate, in addition to adjuvant chemotherapy for breast cancer, and the plasma prolactin level has since normalized.}, } @article {pmid17690508, year = {2007}, author = {Morohashi, S and Odagiri, H and Morohashi, H and Kimura, Y and Sasaki, M}, title = {Complete remission of recurrent breast cancer with multiple liver metastases after oral capecitabine and injected trastuzumab.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {297-301}, doi = {10.2325/jbcs.14.297}, pmid = {17690508}, issn = {1340-6868}, mesh = {Administration, Oral ; Adult ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/diagnostic imaging/*drug therapy/pathology ; Capecitabine ; Carcinoma, Ductal, Breast/diagnostic imaging/*drug therapy/secondary ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage/analogs & derivatives ; Humans ; Injections, Intravenous ; Liver Neoplasms/diagnostic imaging/*drug therapy/secondary ; Neoplasm Recurrence, Local/diagnostic imaging/*drug therapy/pathology ; Radiography ; Trastuzumab ; }, abstract = {A 32-year-old woman underwent modified radical mastectomy for right breast cancer (invasive ductal carcinoma, f, INF beta, v0, ly1, pT2, pN1, M0, Stage II B ER (+/-), PR (-), Her2 (3+)) in June 2003, and received postoperative systemic adjunctive chemotherapy using epirubicin combined with cyclophosphamide, followed by paclitaxel. In August 2004, after a disease-free interval of 14 months, liver metastasis appeared, and therefore from September 2004, combination chemotherapy with oral capecitabine (2,400 mg/day) and injected trastuzumab (120 mg/week) was started. After 3 cycles, all the metastases responded and this marked response has been maintained for 16 months. This therapy is currently being continued (19 cycles), and no serious side effects have been encountered. Capesitabine and trastuzumab combination therapy is effective for recurrent breast cancer showing overexpression of HER2 and resistance to taxane, and can be considered as a first-line therapy for this purpose. It is anticipated that many cases treated with this regimen will be reported and discussed in the near future.}, } @article {pmid17690504, year = {2007}, author = {Nozoe, T and Oyama, T and Mori, E and Uramoto, H and Takenoyama, M and Hanagiri, T and Sugio, K and Yasumoto, K}, title = {Clinicopathologic significance of an immunohistochemical expression of p27 in scirrhous carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {3}, pages = {277-280}, doi = {10.2325/jbcs.14.277}, pmid = {17690504}, issn = {1340-6868}, mesh = {Adenocarcinoma, Scirrhous/*metabolism/pathology ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Case-Control Studies ; Cyclin-Dependent Kinase Inhibitor p27/*metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; }, abstract = {BACKGROUND: Scirrhous carcinoma has been known to have more aggressive biological behavior than other histologic subtypes of invasive ductal carcinoma of the breast. The significance of expression of p27kip1, which is thought to be a tumor suppressor gene, in breast carcinoma remains controversial. The aim of the current study was to clarify clinicopathologic significance of scirrhous carcinoma of the breast with special reference to p27 expression.

METHODS: Clinicopathologic features including immunohistochemical expression of p27 were compared between scirrhous carcinoma (n=42) and non-scirrhous invasive ductal carcinoma (papillotubular and solid-tubular carcinoma, n=63) of the breast.

RESULTS: The proportion of pathologic lymph node metastasis among scirrhous carcinomas was significantly higher than that among carcinomas of other histologic types (papillotubular or solid-tubular carcinomas, p=0.029). The proportion of strong expression of p27 among scirrhous carcinomas was significantly lower than that among tumors of other histologic types (p<0.0001).

CONCLUSIONS: Biological behavior of scirrhous carcinoma was found to be aggressive. The aggressiveness and poor cellular differentiation of scirrhous carcinoma of the breast might be related to low p27 expression.}, } @article {pmid17685448, year = {2008}, author = {Postovit, LM and Abbott, DE and Payne, SL and Wheaton, WW and Margaryan, NV and Sullivan, R and Jansen, MK and Csiszar, K and Hendrix, MJ and Kirschmann, DA}, title = {Hypoxia/reoxygenation: a dynamic regulator of lysyl oxidase-facilitated breast cancer migration.}, journal = {Journal of cellular biochemistry}, volume = {103}, number = {5}, pages = {1369-1378}, doi = {10.1002/jcb.21517}, pmid = {17685448}, issn = {1097-4644}, support = {5 P50 CA089018/CA/NCI NIH HHS/United States ; AR047713/AR/NIAMS NIH HHS/United States ; RR003061/RR/NCRR NIH HHS/United States ; }, mesh = {Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; Cell Hypoxia ; Cell Line, Tumor ; *Cell Movement ; Female ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Neoplastic ; Humans ; Hydrogen Peroxide/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Protein-Lysine 6-Oxidase/*biosynthesis/genetics ; }, abstract = {Fluctuating oxygen levels characterize the microenvironment of many cancers and tumor hypoxia is associated with increased invasion and metastatic potential concomitant with a poor prognosis. Similarly, the expression of lysyl oxidase (LOX) in breast cancer facilitates tumor cell migration and is associated with estrogen receptor negative status and reduced patient survival. Here we demonstrate that hypoxia/reoxygenation drives poorly invasive breast cancer cells toward a more aggressive phenotype by up-regulating LOX expression and catalytic activity. Specifically, hypoxia markedly increased LOX protein expression; however, catalytic activity (beta-aminopropionitrile inhibitable hydrogen peroxide production) was significantly reduced under hypoxic conditions. Moreover, poorly invasive breast cancer cells displayed a marked increase in LOX-dependent FAK/Src activation and cell migration following hypoxia/reoxygenation, but not in response to hypoxia alone. Furthermore, LOX expression is only partially dependent on hypoxia inducible factor-1 (HIF-1alpha) in poorly invasive breast cancer cells, as hypoxia mimetics and overexpression of HIF-1alpha could not up-regulate LOX expression to the levels observed under hypoxia. Clinically, LOX expression positively correlates with tumor progression and co-localization with hypoxic regions (defined by HIF-1alpha expression) in ductal carcinoma in situ and invasive ductal carcinoma primary tumors. However, positive correlation is lost in metastatic tumors, suggesting that LOX expression is independent of a hypoxic environment at later stages of tumor progression. This work demonstrates that both hypoxia and reoxygenation are necessary for LOX catalytic activity which facilitates breast cancer cell migration through a hydrogen peroxide-mediated mechanism; thereby illuminating a potentially novel mechanism by which poorly invasive cancer cells can obtain metastatic competency.}, } @article {pmid17683614, year = {2007}, author = {Dalgin, GS and Alexe, G and Scanfeld, D and Tamayo, P and Mesirov, JP and Ganesan, S and DeLisi, C and Bhanot, G}, title = {Portraits of breast cancer progression.}, journal = {BMC bioinformatics}, volume = {8}, number = {}, pages = {291}, pmid = {17683614}, issn = {1471-2105}, mesh = {Algorithms ; Artificial Intelligence ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis/*metabolism ; Carcinoma, Ductal/*diagnosis/*metabolism ; Diagnosis, Computer-Assisted/methods ; Disease Progression ; Female ; Gene Expression Profiling/*methods ; Humans ; Neoplasm Proteins/*analysis ; Oligonucleotide Array Sequence Analysis/methods ; Pattern Recognition, Automated/methods ; Principal Component Analysis ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Clustering analysis of microarray data is often criticized for giving ambiguous results because of sensitivity to data perturbation or clustering techniques used. In this paper, we describe a new method based on principal component analysis and ensemble consensus clustering that avoids these problems.

RESULTS: We illustrate the method on a public microarray dataset from 36 breast cancer patients of whom 31 were diagnosed with at least two of three pathological stages of disease (atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our method identifies an optimum set of genes and divides the samples into stable clusters which correlate with clinical classification into Luminal, Basal-like and Her2+ subtypes. Our analysis reveals a hierarchical portrait of breast cancer progression and identifies genes and pathways for each stage, grade and subtype. An intriguing observation is that the disease phenotype is distinguishable in ADH and progresses along distinct pathways for each subtype. The genetic signature for disease heterogeneity across subtypes is greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes have distinct progression pathways. Our method identifies six disease subtype and one normal clusters. The first split separates the normal samples from the cancer samples. Next, the cancer cluster splits into low grade (pathological grades 1 and 2) and high grade (pathological grades 2 and 3) while the normal cluster is unchanged. Further, the low grade cluster splits into two subclusters and the high grade cluster into four. The final six disease clusters are mapped into one Luminal A, three Luminal B, one Basal-like and one Her2+.

CONCLUSION: We confirm that the cancer phenotype can be identified in early stage because the genes altered in this stage progressively alter further as the disease progresses through DCIS into IDC. We identify six subtypes of disease which have distinct genetic signatures and remain separated in the clustering hierarchy. Our findings suggest that the heterogeneity of disease across subtypes is higher than the heterogeneity of the disease progression within a subtype, indicating that the subtypes are in fact distinct diseases.}, } @article {pmid17682561, year = {2007}, author = {Al-Joudi, FS and Iskandar, ZA and Imran, AK}, title = {Survivin expression correlates with unfavourable prognoses in invasive ductal carcinoma of the breast.}, journal = {The Medical journal of Malaysia}, volume = {62}, number = {1}, pages = {6-8}, pmid = {17682561}, issn = {0300-5283}, mesh = {Breast Neoplasms/*physiopathology ; Carcinoma, Ductal, Breast/*physiopathology ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Medical Audit ; Microtubule-Associated Proteins/*analysis/antagonists & inhibitors ; Neoplasm Proteins/*analysis/antagonists & inhibitors ; Prognosis ; Survivin ; }, abstract = {Survivin is a 16.5-kDa intracellular protein also known as AP14 or BIRC5. It inhibits apoptosis and regulates cell division and belongs to the inhibitors of apoptosis (IAP) gene family. In the majority of neoplasms investigated for survivin expression, high levels of the IAP proteins were predictive of tumour progression, either in terms of disease-free survival or overall survival, thus providing significant prognostic information. Hence, the prognostic value of survivin expression in tumour masses of invasive ductal carcinoma has been investigated. It was found that negative and low expression of survivin correlated significantly with favourable outcomes. Conversely, high expression correlated with unfavourable outcomes. The five-year survival rate was higher among the cases with low and negative survivin expression, compared to those with higher survivin expression. However, this correlation was found to be insignificant statistically. Furthermore, a statistical model has been devised to explain the combined effects of survivin expression and its sub-cellular localisation, p-53 expression and lymph nodal involvement, on the outcomes of these patients.}, } @article {pmid17676086, year = {2007}, author = {McFadden, AM and Wang, J and Mackereth, GF and Clough, RR and Loth, LH and Vermunt, JJ and King, CM and Alley, MR}, title = {Non-systemic erosive stomatitis of unknown aetiology in a dairy cow herd in New Zealand.}, journal = {New Zealand veterinary journal}, volume = {55}, number = {4}, pages = {198-202}, doi = {10.1080/00480169.2007.36768}, pmid = {17676086}, issn = {0048-0169}, mesh = {Animals ; Bacterial Infections/diagnosis/pathology/veterinary ; Cattle ; Cattle Diseases/*etiology/*pathology ; Diagnosis, Differential ; Female ; Immunohistochemistry/veterinary ; New Zealand ; Polymerase Chain Reaction/methods/veterinary ; Stomatitis/etiology/pathology/*veterinary ; Virus Diseases/diagnosis/pathology/veterinary ; }, abstract = {CASE HISTORY: Veterinarians from the Investigation and Diagnostic Centre (IDC), Wallaceville, New Zealand, investigated a novel vesicular disease in a 397-cow dairy herd, characterised by erosive stomatitis.

The investigation commenced with a report of erosive stomatitis in four dairy cows. The herd was examined that day and 30/397 (8%) adult cows were found to be affected. Two weeks later, the oral cavity of 180 cows from one management group were re-examined, and it was estimated that 80% of this group had healing erosive lesions. During the course of the investigation, intact vesicles were observed on the muzzle of two affected animals. None of the affected animals was systemically ill and there was no decrease in milk production.

DIAGNOSIS: No infectious aetiological agent was detected using virus isolation, polymerase chain reaction (PCR), electron microscopy (EM) and serological tests, for any exotic infectious vesicular disease or any endemic cause of vesicular disease.

CLINICAL RELEVANCE: Lesions of erosive stomatitis occurring in cattle must be differentiated from vesicular disease during exotic disease investigations.}, } @article {pmid17674195, year = {2008}, author = {Uematsu, T and Kasami, M}, title = {Risk of needle tract seeding of breast cancer: cytological results derived from core wash material.}, journal = {Breast cancer research and treatment}, volume = {110}, number = {1}, pages = {51-55}, doi = {10.1007/s10549-007-9685-6}, pmid = {17674195}, issn = {0167-6806}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle/*adverse effects ; Breast Neoplasms/*pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Lobular/pathology ; Female ; Humans ; Middle Aged ; *Neoplasm Seeding ; }, abstract = {Needle track seeding has been recognized as a possible, albeit rare, complication of breast core needle biopsy. The purpose of this study was to assess the risk of needle tract seeding of breast cancer from cytological results derived from core needle wash material. The study included biopsies of 207 breast cancers performed using ultrasonographically guided 18-gauge core needles. Each core needle without exposed sample notch was washed in saline solution immediately after removing the needles. Cytology derived from core wash material was performed by saline solution lavage of the fragments using a cytocentrifuge. The cytological diagnoses were divided into five categories: benign, atypical/indeterminate, suspicious/probably malignant, malignant and unsatisfactory. Atypical/indeterminate, suspicious/probably malignant and malignant categories were considered to represent positive cases of needle track seeding of breast cancer, whereas benign and unsatisfactory categories were counted as negative cases. Cytological diagnoses of the 207 lesions were as follows: 26 lesions (12%) were benign, 18 lesions (9%) were atypical/indeterminate, 37 lesions (18%) were suspicious/probably malignant, 79 lesions (38%) were malignant, and 47 lesions (23%) were unsatisfactory. The incidence of positive cases of cytology derived from core wash material was 65% (134/207). The 25% frequency of positive cases of invasive lobular carcinoma was significantly lower than the frequencies of DCIS (74%) and invasive ductal carcinoma (69%) (P = 0.001 and P < 0.01). The frequency of positive cases in the multiple passes group was 75%, which was slightly, although not significantly, higher than the 66% frequency in the single pass group (P = 0.3). In conclusion, the incidence of positive cases of cytology derived from ultrasonographically guided breast core needles' wash material was 65%. The clinical significance is debatable; however, there may be a theoretical risk of local recurrence if the tract is not excised or radiotherapy not given.}, } @article {pmid17666645, year = {2007}, author = {Sekar, R and Stone, PR}, title = {Trastuzumab use for metastatic breast cancer in pregnancy.}, journal = {Obstetrics and gynecology}, volume = {110}, number = {2 Pt 2}, pages = {507-510}, doi = {10.1097/01.AOG.0000267133.65430.44}, pmid = {17666645}, issn = {0029-7844}, mesh = {Adult ; Antibodies, Monoclonal/adverse effects/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Brachial Plexus Neuropathies/drug therapy ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Ductal, Breast/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Docetaxel ; Female ; Humans ; Infant, Newborn ; Lung Neoplasms/drug therapy/secondary ; Neoplasm Staging ; Oligohydramnios/*chemically induced ; Pregnancy ; Pregnancy Complications, Neoplastic/*drug therapy/pathology ; Pregnancy Outcome ; Taxoids/adverse effects/therapeutic use ; Trastuzumab ; }, abstract = {BACKGROUND: Trastuzumab is approved for first-line treatment for breast cancer in combination with docetaxel for stage 2 tumors positive for human epidermal growth factor receptor 2. The effects of trastuzumab on the fetus are mostly unknown.

CASE: Our case report focuses on a woman who was treated for invasive ductal carcinoma 1 year before pregnancy. She presented at 20 weeks of gestation with metastases and was treated with docetaxel and trastuzumab. She underwent two cycles of chemotherapy, and an ultrasound scan at 30 weeks showed anhydramnios. There was no history of ruptured membranes. Reappearance of amniotic fluid was noted at 33 weeks of gestation, 7 weeks after cessation of treatment.

CONCLUSION: Treatment with trastuzumab during midgestation may be associated with anhydramnios.}, } @article {pmid17664621, year = {2007}, author = {Palacios, M and Friedrich, H and Götze, C and Vallverdú, M and de Luna, AB and Caminal, P and Hoyer, D}, title = {Changes of autonomic information flow due to idiopathic dilated cardiomyopathy.}, journal = {Physiological measurement}, volume = {28}, number = {6}, pages = {677-688}, doi = {10.1088/0967-3334/28/6/006}, pmid = {17664621}, issn = {0967-3334}, mesh = {Adult ; Autonomic Nervous System/*physiopathology ; Cardiomyopathy, Dilated/*physiopathology ; Case-Control Studies ; Heart Rate/physiology ; Humans ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {Risk stratification of patients with idiopathic dilated cardiomyopathy (IDC) is an epidemiologically relevant question. But the results based on conventional heart rate variability (HRV) analysis are still unsatisfactory. The adjustments within the cardiovascular system incorporate nonlinear and complex mechanisms of information exchange which may have additional prognostic value. It is an objective of the present work to evaluate the prognostic value of autonomic information flow (AIF) measures in IDC patients compared to conventional HRV measures in a first explorative study. Holter recordings of 32 patients with idiopathic dilated cardiomyopathy (IDC) and 12 normal subjects (NRM) were analyzed. The IDC patients consisted of two groups: 10 high risk (HR) patients, after aborted sudden cardiac death (SCD); 22 low risk (LR) patients, without SCD. Sensitivity, specificity, positive predictive value, negative predictive value and ROC characteristics of a comprehensive set of AIF measures, organized according to the conventional HRV standards, and conventional HRV measures were investigated. The significant risk predictors were evaluated by Spearman's rank correlation. While the only traditional HRV measure discriminating IDC patients from NRM was ln(LF) most of the AIF measures had a discriminatory value. Concerning the prognosis of the IDC patients by conventional HRV we found that SDNN and all frequency band measures (lnHF, lnLF, lnVLF) significantly discriminated HR from LR. Among the AIF measures the time shift related peak decay (PD(dHF)) reflecting the HF band information flow had a prognostic value. PD(dHF) was identified as a promising candidate which might improve the predictive value of traditional HRV analysis, predominantly represented by SDNN. A subsequent comprehensive clinical study is necessary to validate this hypothesis.}, } @article {pmid17659933, year = {2007}, author = {Fukunaga, T and Soejima, H and Irie, A and Sugamura, K and Oe, Y and Tanaka, T and Nagayoshi, Y and Kaikita, K and Sugiyama, S and Yoshimura, M and Nishimura, Y and Ogawa, H}, title = {Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {100}, number = {3}, pages = {483-488}, doi = {10.1016/j.amjcard.2007.03.052}, pmid = {17659933}, issn = {0002-9149}, mesh = {Aged ; C-Reactive Protein/analysis ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Cardiomyopathy, Dilated/*complications ; Female ; Flow Cytometry ; Heart Failure/blood/etiology/*immunology/physiopathology ; Heart Rate ; Humans ; Interferon-gamma/metabolism ; Interleukin-4/metabolism ; Male ; Middle Aged ; Myocardial Ischemia/*complications ; Natriuretic Peptide, Brain/blood ; Stroke Volume ; Tumor Necrosis Factor-alpha/analysis ; }, abstract = {The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.}, } @article {pmid17658224, year = {2007}, author = {Oka, K and Sando, N and Moriya, T and Yatabe, Y}, title = {Malignant adenomyoepithelioma of the breast with matrix production may be compatible with one variant form of matrix-producing carcinoma: a case report.}, journal = {Pathology, research and practice}, volume = {203}, number = {8}, pages = {599-604}, doi = {10.1016/j.prp.2007.04.004}, pmid = {17658224}, issn = {1618-0631}, mesh = {Adenocarcinoma, Mucinous/pathology/surgery ; Adenomyoepithelioma/metabolism/*pathology ; Aged ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/pathology/surgery ; Extracellular Matrix ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Multiple Primary/metabolism/*pathology ; Rectal Neoplasms/pathology/surgery ; Stroke/complications ; }, abstract = {We examined a 77-year-old woman who suffered from a left breast tumor. She had undergone right mastectomy for invasive ductal carcinoma at 68 years of age, and rectal resection for mucinous carcinoma at the age of 74 years. The left breast tumor measured 3.8 x 2.5 x 1.6 cm. Neoplastic cells consisted of atypical epithelial and myoepithelial cells. The former cells were polygonal and large. They were located in the periphery of the tumor, arranged in a ductal pattern, and expressed cytokeratins, S-100 protein, maspin, and MIC2. The latter cells were composed of dark cells which proliferated in a periductal pattern, and stellate cells which were located in the center of the tumor. They invaded the chondromyxoid tissues, and proliferated in a lace-like pattern. Atypical myoepithelial cells expressed vimentin, S-100 protein, maspin, and MIC2. We conclude that malignant adenomyoepithelioma of the breast with matrix production might be compatible with a variant form of matrix-producing carcinoma.}, } @article {pmid17652893, year = {2007}, author = {Ohta, S and Shinke, T and Hata, K and Takaoka, H and Shite, J and Kijima, Y and Murata, T and Yoshikawa, R and Masai, H and Hirata, K and Yokoyama, M}, title = {Inhibition of endogenous nitric oxide synthase augments contractile response to adenylyl cyclase stimulation without altering mechanical efficiency in patients with idiopathic dilated cardiomyopathy.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {71}, number = {8}, pages = {1268-1273}, doi = {10.1253/circj.71.1268}, pmid = {17652893}, issn = {1346-9843}, mesh = {Adenylyl Cyclases/*pharmacology ; Adrenergic beta-Agonists ; Aged ; Biomechanical Phenomena ; Cardiomyopathy, Dilated/*complications ; Colforsin/administration & dosage/analogs & derivatives ; Female ; Heart Failure/etiology ; Heart Function Tests ; Humans ; Male ; Middle Aged ; Myocardial Contraction/*drug effects ; Nitric Oxide Synthase Type III/*antagonists & inhibitors ; omega-N-Methylarginine/administration & dosage/pharmacology ; }, abstract = {BACKGROUND: Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure.

METHODS AND RESULTS: The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency.

CONCLUSIONS: These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.}, } @article {pmid17652529, year = {2007}, author = {Khilko, N and Bourne, P and Qi Yang, and Ping Tang, }, title = {Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis.}, journal = {International journal of surgical pathology}, volume = {15}, number = {3}, pages = {233-241}, doi = {10.1177/1066896907302116}, pmid = {17652529}, issn = {1066-8969}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/physiology ; Breast Neoplasms/*genetics/pathology/physiopathology ; Carcinoma, Ductal, Breast/*genetics/pathology/physiopathology ; *DNA Mismatch Repair ; DNA, Neoplasm/genetics ; ErbB Receptors/genetics/physiology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Keratins/genetics/physiology ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/*genetics/physiology ; Nuclear Proteins/*genetics/physiology ; Receptor, ErbB-2/genetics/physiology ; Receptors, Estrogen/genetics/physiology ; Receptors, Progesterone/genetics/physiology ; }, abstract = {Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-alpha (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases>50 years, 54 cases<50 years), tumor size (31 cases of IDC>2 cm, 90 cases of IDC<2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.}, } @article {pmid17646371, year = {2007}, author = {Glazebrook, KN and Morton, MJ and Reynolds, C}, title = {Carcinoma of the breast mimicking an areolar dermal lesion.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {26}, number = {8}, pages = {1083-1087}, doi = {10.7863/jum.2007.26.8.1083}, pmid = {17646371}, issn = {0278-4297}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Sebaceous Glands/*pathology ; Skin Diseases/diagnostic imaging/pathology ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: This report describes the sonographic features of 2 patients with invasive carcinoma of the breast that sonographically mimicked benign epithelial cysts of the areola.

METHODS: We retrospectively reviewed 2 cases of invasive ductal carcinoma that initially were diagnosed as dermal lesions in the areola after sonographic evaluation.

RESULTS: Sonographically, the 2 lesions were centered between the echogenic lines of the deep dermis of the areola. Neither sonogram showed a deeper component arising from the underlying breast tissue that would suggest a breast origin.

CONCLUSIONS: Lesions in the subcutaneous tissue superficial to the anterior pectoral fascia are extraparenchymal in origin and typically are benign. The areolar tissue, however, is not extraparenchymal because the dermis of the areola contains lactiferous ducts; these ducts extend from a more deeply placed mammary gland and are associated with modified sebaceous glands. All types of breast abnormalities, including malignancies, may affect deeper lactiferous glands and ducts and extend into the areola, independent of nipple involvement.}, } @article {pmid17645853, year = {2007}, author = {Zhao, WH and Xu, BH and Zhang, P and Li, Q and Zhao, LM and Sun, Y}, title = {[Clinical characteristics and prognosis of breast cancer patients with vascular invasion].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {29}, number = {2}, pages = {137-140}, pmid = {17645853}, issn = {0253-3766}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry/statistics & numerical data ; Lymphatic Metastasis ; Mastectomy/methods ; Middle Aged ; Neoplasm Staging ; Neoplastic Cells, Circulating/metabolism/*pathology ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {OBJECTIVE: To analyze the clinicopathological features, parameters of molecular biology, survival rate, and prognostic factors in breast cancer patients with vascular invasion.

METHODS: The data of 262 breast cancer patients with vascular invasion surgically treated between January 1995 and December 2003 in our institution were retrospectively analyzed. Clinicopathological characteristics, parameters of molecular biology, disease free survival rate and overall survival rate were surveyed.

RESULTS: Of all breast cancer patients registered in our institution during the same period, these 262 breast cancer patients with vascular invasion accounted for 5.3% with a median age of 43 years. The major pathological type was invasive ductal carcinoma (93.3%). The stages included stage I in 5% , stage II 31. 3% , stage III 58.8% , stage IV 1.1% , and unknown 3.8%. Immunohistochemical staining showed that ER positive in 67.7%, PR(+) 68.0%, p53(+) 54.2%, PCNA(+) 93.3%, c-erbB2(+++) 20.8% and c-erbB2(++) 16.9%. The 5-year and 10-year cumulative disease free survival and overall survival were 57.6% , 50.7% and 62.8%, 52.9% , respectively. The factors which were found to compromise disease free survival were the tumor size, lymph node status, stage, and radiotherapy in the univariate analysis, and for overall survival, were the tumor size, lymph node status, stage, location of vascular invasion and radiotherapy. The tumor size and radiotherapy were found to be independent prognostic factors for disease free survival and overall survival in the multivariate analysis.

CONCLUSION: Breast cancers with vascular invasion have poor biological behavior though having been treated by surgery, radiotherapy and chemotherapy. The independent prognostic factors of such patients are tumor size and radiotherapy. Anti-angiogenesis and antilymphangiogenesis may gradually become promising target treatment for such patient.}, } @article {pmid17645766, year = {2007}, author = {Zaguri, R and Verbovetski, I and Atallah, M and Trahtemberg, U and Krispin, A and Nahari, E and Leitersdorf, E and Mevorach, D}, title = {'Danger' effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells.}, journal = {Clinical and experimental immunology}, volume = {149}, number = {3}, pages = {543-552}, pmid = {17645766}, issn = {0009-9104}, mesh = {Antigens, CD/blood ; Apoptosis/drug effects ; B7-2 Antigen/blood ; Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*drug effects ; HLA-DR Antigens/blood ; Humans ; Immunoglobulins/blood ; Lipoproteins, LDL/*pharmacology ; Membrane Glycoproteins/blood ; Phagocytosis/immunology ; Receptors, CCR7 ; Receptors, Chemokine/blood ; }, abstract = {Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.}, } @article {pmid17645728, year = {2007}, author = {Ninomiya, K and Ohi, S and Tabei, I and Jin, S and Tachibana, T and Yamashita, S and Yanaga, K and Hashimoto, H}, title = {Establishment and characterization of a cell line (BTIC) including HER-2-positive cells derived from pleural effusion of recurrent breast invasive ductal carcinoma, scirrhous type.}, journal = {Human cell}, volume = {20}, number = {3}, pages = {85-90}, pmid = {17645728}, issn = {0914-7470}, mesh = {Adult ; Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology ; *Cell Line, Tumor ; Chemotherapy, Adjuvant ; Female ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Karyotyping ; Mice ; Mice, Nude ; Microscopy, Electron ; Neoplasm Recurrence, Local ; Neoplasm Transplantation ; Pleural Effusion/*pathology ; Transplantation, Heterologous ; Trastuzumab ; }, abstract = {Human epidermal growth factor receptor-2 (HER-2) overexpression in breast cancer occurs in 20% to 30% of patients with breast cancer. Trastuzumab (Herceptin) targets HER-2 tyrosine kinase receptors expressed on tumor cells and mediates anti-proliferative effects against HER-2-positive tumor cells. Adjuvant chemotherapy with trastuzumab has improved the prognosis of patients with HER-2 positive high-grade breast cancer. However, patients often experience appearance and proliferation of recurrent tumor cells after trastuzumab treatment. In this study, we report the successful establishment and characterization of a cell line (BTIC) derived from a patient with recurrent breast cancer after adjuvant chemotherapy with trastuzumab. Characteristics of the BTIC cell line were investigated by phase contrast or electron microscopic observations, chromosome analysis, xenotransplantation, immunohistochemistry and radioimmunoassay for tumor markers. We confirmed that the BTIC cell line grown as multilayered culture in culture dishes, has a poorly developed endoplasmic reticulum in the cytoplasm and some desmosomes. The population doubling time was approximately 44 hr. A graft in nude mouse after xenotransplantation was diagnosed as scirrhous carcinoma. Immunohistochemistry on cultured BTIC cells revealed that the BTIC cells were negative for estrogen receptor and progesterone receptor, and 30% positive for HER-2. Radioimmunoassay indicated secretion of HER-2 protein, NCC-ST-439 and CA15-3.}, } @article {pmid17642161, year = {2007}, author = {Peihong, S and Perry, F}, title = {Expression of nm23, MMP-2, TIMP-2 in breast neoplasm in Zhengzhou Center Hospital, China.}, journal = {Ethiopian medical journal}, volume = {45}, number = {1}, pages = {79-83}, pmid = {17642161}, issn = {0014-1755}, mesh = {Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/enzymology ; Carcinoma in Situ/*drug therapy/enzymology ; Carcinoma, Ductal/*drug therapy/enzymology ; Carcinoma, Ductal, Breast/*drug therapy/enzymology ; China ; Female ; Fibroadenoma/*drug therapy/enzymology ; Humans ; Matrix Metalloproteinase 9/metabolism ; Matrix Metalloproteinases, Membrane-Associated/*therapeutic use ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Metastasis ; Nucleoside-Diphosphate Kinase/*metabolism ; Prospective Studies ; Tissue Inhibitor of Metalloproteinase-2 ; }, abstract = {BACKGROUND: In recent years, the carcinoma of the breast threatens to women's health heavily. Invasion and metastasis is the main reason that results in the patients death.

OBJECTIVE: A prospective study is made in the center hospital of zhengzhou, in order to approach the expression of nm23, MMP-2 (Matrix metallo-proteinase-2), TIMP-2 (it's tissue-inhibitor of the metalloproteinase-2) in the breast neoplasm and the relationship with invasion and metastasis.

METHODOLOGY: This study applied the immunohistochemistry technique SP method

RESULTS: In fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma of the breast 4 groups, the positive immunostaining rate of nm23, MMP-2 and TIMP-2 have significant difference among 4 groups (p < 0.05). In the breast invasive ductal carcinoma, the expression of nm23 and TIMP-2 decreased or the expression of MMP-2 increased

CONCLUSION: This suggested that invasion and metastasis is ability of the neoplasm. MMP-2 in the breast ductal carcinoma in situ appears of high expression and this suggested that the positive expression of this onco-proteins was the early incident in the genetic course of the breast cancer The unite detection of nm23, MMP-2 and TIMP-2 expression would contribute to the early diagnosis and prognostic assessment of the carcinoma of the breast.}, } @article {pmid17640306, year = {2007}, author = {Feng, R and Liu, X and Guo, Z and Li, J}, title = {Purification and characterization of 66-kDa glycoprotein from human breast carcinoma.}, journal = {Cancer science}, volume = {98}, number = {9}, pages = {1344-1349}, doi = {10.1111/j.1349-7006.2007.00539.x}, pmid = {17640306}, issn = {1347-9032}, mesh = {Amino Acid Sequence ; Animals ; Biomarkers, Tumor/chemistry/*isolation & purification ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Cell Line, Tumor ; Female ; Glycoproteins/chemistry/*isolation & purification ; Humans ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Neoplasm Proteins/chemistry/*isolation & purification ; Peptide Fragments/chemistry ; Protein Precursors/chemistry ; Serum Albumin/chemistry ; }, abstract = {We extracted a 66-kDa glycoprotein (GP-1D8) from breast invasive ductal carcinoma tissues. The monoclonal antibody (mAb) against GP-1D8 was prepared in our laboratory. Western blotting with the purified protein using the mAb demonstrated a single band of 66 kDa. Immunocytochemical and immunohistochemical analysis revealed strong expression of GP-1D8 protein in the cytoplasm of MCF-7 cells and different types of breast carcinoma tissues, but GP-1D8 is absent in normal breast and benign breast tumor tissues. Glycosylation analysis showed GP-1D8 contained methylated salic acid. GP-1D8 was identified using mass-spectrometric techniques and N-terminal sequencing. These data were used to identify the protein through the SWISSPROT protein sequence database and BLAST homology search. These results showed GP-1D8 had some similarity to human albumin precursor. Co-immunoprecipitation assays of lysate from MCF-7 cells and mass spectrometric analysis revealed the interaction of GP-1D8 with beta-tubulin. This is the first time human breast carcinoma tissues and MCF-7 cells have been shown to express a 66-kDa glycoprotein similar to human albumin precursor. These results might be important in the detection of novel potential biomarkers and may provide insight into the molecular mechanisms of tumorigenesis.}, } @article {pmid17638621, year = {2007}, author = {Kuo, WH and Chang, LY and Liu, DL and Hwa, HL and Lin, JJ and Lee, PH and Chen, CN and Lien, HC and Yuan, RH and Shun, CT and Chang, KJ and Hsieh, FJ}, title = {The interactions between GPR30 and the major biomarkers in infiltrating ductal carcinoma of the breast in an Asian population.}, journal = {Taiwanese journal of obstetrics & gynecology}, volume = {46}, number = {2}, pages = {135-145}, doi = {10.1016/S1028-4559(07)60007-2}, pmid = {17638621}, issn = {1875-6263}, mesh = {Asian People ; Biomarkers, Tumor/metabolism ; Breast/metabolism ; Breast Neoplasms/*metabolism/mortality ; Carcinoma, Ductal, Breast/*metabolism/mortality ; Down-Regulation ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Prognosis ; Proportional Hazards Models ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen ; Receptors, G-Protein-Coupled/*metabolism ; Receptors, Progesterone/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Taiwan/epidemiology ; }, abstract = {OBJECTIVE: G-protein-coupled receptor 30 (GPR30) has been reported to be a novel estrogen receptor alpha (ERalpha) in vitro. Therefore, the interactions among GPR30, ERalpha, progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2/neu), and their prognostic utilities in the infiltrating ductal carcinoma (IDC) of the breast were evaluated.

MATERIALS AND METHODS: Messenger RNA (mRNA) levels of GPR30, ERalpha, PR and HER-2/neu in the tumor samples of 118 Taiwanese IDC patients and 27 non-tumor mammary tissues were measured via quantitative polymerase chain reaction analyses. The correlations of GPR30 mRNA levels with clinical parameters, i.e. tumor/non-tumor, ERalpha, PR, HER-2/neu, age, lymph node metastasis, lymph-vascular invasion, grade, stage and patient survival, were assessed by using appropriate statistical analyses.

RESULTS: GPR30 expression was observed to be lower in IDC (p < 0.001) than in non-tumor mammary tissues. Importantly, GPR30 mRNA level was positively correlated with that of ERalpha (p = 0.001) and PR (p = 0.001) but not correlated with that of HER-2/neu when they were analyzed as continuous variables. However, lower GPR30 was noticed in tumors with HER-2/neu protein overexpression. GPR30 expression was not correlated with age, lymph node metastasis, lymph-vascular invasion, grade and stage in IDC. GPR30 expression was not an independent prognostic factor for patient survival.

CONCLUSION: GPR30 expression is downregulated in IDC. GPR30 is preferentially co-expressed with ER and/or PR but is lowly expressed in HER-2/neu(+) tumors. The correlation of GPR30 expression with clinical parameters, including patient survival, was not evident in this cohort.}, } @article {pmid17617471, year = {2007}, author = {Wang, YS and Chi, KH and Chu, RM}, title = {Cytokine profiles of canine monocyte-derived dendritic cells as a function of lipopolysaccharide- or tumor necrosis factor-alpha-induced maturation.}, journal = {Veterinary immunology and immunopathology}, volume = {118}, number = {3-4}, pages = {186-198}, doi = {10.1016/j.vetimm.2007.05.010}, pmid = {17617471}, issn = {0165-2427}, mesh = {Animals ; Cell Differentiation/*drug effects ; Cytokines/*genetics/*metabolism ; Dendritic Cells/cytology/*drug effects/*metabolism ; Dogs ; Flow Cytometry/veterinary ; Gene Expression Regulation/drug effects ; Interferons/genetics/metabolism ; Interleukins/genetics/metabolism ; Lipopolysaccharides/*pharmacology ; Monocytes/cytology/drug effects ; Th1 Cells/drug effects/metabolism ; Th2 Cells/drug effects/metabolism ; Tumor Necrosis Factor-alpha/*pharmacology ; }, abstract = {In response to exogenous as well as endogenous signals, dendritic cells (DC) undergo programmed maturation to become efficient, antigen-presenting cells and mediate innate and adaptive immune responses. Very little is known, however, about the differential maturation responses of canine DC to endogenous and exogenous stimuli, especially the concomitant events related to the specific expression of cytokine genes. Canine monocyte-derived immature DC (iDC) were treated with an exogenous signal, bacterial lipopolysaccharide (LPS), or an endogenous signal, tumor necrosis factor-alpha (TNF-alpha), to generate mature DC (mDC). The mDC generated from either stimuli were characterized by significant increases in the expression of surface molecules, including CD11c, MHC class II, CD80, CD83, and CD86. Using real-time reverse transcriptase polymerase chain reactions, the cytokine expression profiles generated by these two stimuli were studied. Compared with the iDC, the LPS-stimulated mDC exhibited a significantly increased expression of IL-1 beta, IL-10, IL-12p40, IL-13, and TNF-alpha. Using the mixed lymphocyte reaction and cytokine intracellular staining, it was shown that the array of cytokines from LPS-generated mDC contributed to T cell priming and T helper cell type 1 (Th1) polarization. TNF-alpha-generated mDC increased the expression of a distinctly different panel of cytokines, namely IL-2, IL-4, IL-12p40, IL-13, TNF-alpha, TGF-beta, IFN-gamma, and MCP-2, and shifted naïve T cell differentiation to T helper cell type 2 (Th2) polarization. IL-13 expression was dramatically increased in canine TNF-alpha-generated mDC, which does not occur in other mammalian species, including humans. Because IL-13 is functionally similar to IL-4, IL-13 may contribute to the observed Th2 polarization. Thus, canine DC maturing from different stimuli release different cytokine profiles that in turn promote different immune responses and activate innate and adaptive immune responses.}, } @article {pmid17617002, year = {2007}, author = {Cohen, RJ and Shannon, BA and Weinstein, SL}, title = {Intraductal carcinoma of the prostate gland with transmucosal spread to the seminal vesicle: a lesion distinct from high-grade prostatic intraepithelial neoplasia.}, journal = {Archives of pathology & laboratory medicine}, volume = {131}, number = {7}, pages = {1122-1125}, doi = {10.5858/2007-131-1122-ICOTPG}, pmid = {17617002}, issn = {1543-2165}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*pathology ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Prostatic Intraepithelial Neoplasia/*pathology ; Prostatic Neoplasms/*pathology ; Seminal Vesicles/*pathology ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) gland represents an intraluminal neoplastic proliferation that is distinct from high-grade prostatic intraepithelial neoplasia (HG-PIN) and almost always coexists with large-volume, high-stage, and high-grade invasive carcinoma. We document an unusual presentation of apparently "early" IDC-P without an aggressive invasive element that, despite being confined to the acinar-ductal system, has gained access to the ejaculatory duct and seminal vesicle by transmucosal spread. This finding confirms that IDC-P, in contrast to HG-PIN, is inherently aggressive and has the ability to spread beyond the prostate gland. In this case, the absence of an aggressive invasive element suggests that IDC-P has most likely evolved within the lumens directly from HG-PIN.}, } @article {pmid17616999, year = {2007}, author = {Cohen, RJ and Wheeler, TM and Bonkhoff, H and Rubin, MA}, title = {A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {131}, number = {7}, pages = {1103-1109}, doi = {10.5858/2007-131-1103-APOTIH}, pmid = {17616999}, issn = {1543-2165}, mesh = {Biopsy ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology ; Humans ; Male ; Prognosis ; Prostate/pathology ; Prostatic Intraepithelial Neoplasia/diagnosis/*pathology ; Prostatic Neoplasms/diagnosis/*pathology ; }, abstract = {CONTEXT: Prostatic adenocarcinoma growing within acinar-ductal spaces (intraductal carcinoma) in contrast to high-grade prostatic intraepithelial neoplasia (HG-PIN) impacts negatively on patient outcome. There is currently no generally accepted definition of this lesion nor is it classified in the current prostate cancer grading system (Gleason).

OBJECTIVE: To define intraductal carcinoma of the prostate (IDC-P) with major and minor diagnostic criteria that clearly separate it from HG-PIN. The implications of such a lesion are discussed with proposals to incorporate this entity into the Gleason grading system.

DATA SOURCES: We reviewed all published data referring to intraductal spread of prostate carcinoma. Articles discussing endometrial, endometrioid, and ductal carcinoma are included.

CONCLUSIONS: Intraductal carcinoma of the prostate as defined by major criteria that include enlarged gland structures, neoplastic cells spanning the gland lumen, central comedonecrosis, and further supported by minor diagnostic criteria including molecular biological markers, separate this entity from HG-PIN. Despite its perimeter basal cells, IDC-P should be interpreted as biologically equivalent to Gleason pattern 4 or 5 adenocarcinoma. Several hypotheses are proposed as to the evolution of IDC-P, which is almost always a late event in prostate carcinoma progression. Diagnosis of IDC-P on needle biopsy should prompt therapeutic intervention rather than surveillance or repeat biopsy, as is the case for HG-PIN.}, } @article {pmid17611039, year = {2007}, author = {Zagouri, F and Sergentanis, TN and Nonni, A and Koulocheri, D and Fotou, M and Panopoulou, E and Panou, M and Fotiadis, C and Bramis, J and Zografos, GC}, title = {Vacuum-assisted breast biopsy: the value and limitations of cores with microcalcifications.}, journal = {Pathology, research and practice}, volume = {203}, number = {8}, pages = {563-566}, doi = {10.1016/j.prp.2007.05.001}, pmid = {17611039}, issn = {1618-0631}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/*methods ; Breast Neoplasms/*pathology/*surgery ; Calcinosis/*pathology/*surgery ; Female ; Humans ; Middle Aged ; Precancerous Conditions/pathology/surgery ; Retrospective Studies ; Vacuum ; }, abstract = {The aim of this study was to assess cores with microcalcifications (CM) and without microcalcifications (CWM) obtained from vacuum-assisted breast biopsy (VABB). The study included 12 atypical ductal hyperplasias (ADH), 37 ductal carcinomas in situ (DCIS), and seven invasive ductal carcinomas (IDC) diagnosed by VABB (11G) on the Fischer's table. More than 24 cores were excised. For CM/CWM, a separate pathology report was given. Open surgery followed, and underestimation was calculated. The CM/CWM discrepancy was evaluated (superiority, identity, and inferiority). CWM failed to make the diagnosis in 8.3% and 35.1% of ADH and DCIS, respectively. In 28.6% of IDC, diagnosis was made through CWM. CM volume was 1.2+/-0.3 cm(3) for the two IDCs missed by CM, 1.0+/-0.4 cm(3) for the 40 cases of identical diagnoses, and 1.4+/-0.5 cm(3) for the 14 cases of CM superiority (p=0.048, Kruskal-Wallis test). CWM volume was 6.3+/-1.8 cm(3) for the two IDCs missed by CM, 2.6+/-1.8 cm(3) for cases with identical diagnoses, and 3.4+/-1.6 cm(3) for cases of CM superiority (p=0.018, Kruskal-Wallis test). The underestimation rate was 8.3% in ADH, and 10.8% in DCIS. CMs are superior in DCIS/ADH diagnosis. However, CWM may be valuable for the diagnosis of the invasive component.}, } @article {pmid17609820, year = {2007}, author = {Al-Joudi, FS and Iskandar, ZA and Hasnan, J and Rusli, J and Kamal, Y and Imran, AK and Ahmed, M and Zakaria, J}, title = {Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast.}, journal = {Singapore medical journal}, volume = {48}, number = {7}, pages = {607-614}, pmid = {17609820}, issn = {2737-5935}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asia, Southeastern ; Breast Neoplasms/ethnology/*metabolism/pathology ; Carcinoma, Ductal, Breast/ethnology/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Lymphatic Metastasis ; Microtubule-Associated Proteins/*metabolism ; Middle Aged ; Neoplasm Proteins/*metabolism ; Survivin ; }, abstract = {INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.

METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.

RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.

CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.}, } @article {pmid17607371, year = {2007}, author = {Sanada, Y and Yoshida, K and Ohara, M and Tsutani, Y}, title = {Expression of orotate phosphoribosyltransferase (OPRT) in hepatobiliary and pancreatic carcinoma.}, journal = {Pathology oncology research : POR}, volume = {13}, number = {2}, pages = {105-113}, pmid = {17607371}, issn = {1219-4956}, mesh = {Adenocarcinoma/*enzymology/pathology ; Aged ; Carcinoma in Situ/*enzymology/pathology ; Carcinoma, Hepatocellular/*enzymology/pathology ; Female ; Gallbladder/enzymology/pathology ; Gallbladder Neoplasms/*enzymology/pathology ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Liver/enzymology/pathology ; Liver Neoplasms/*enzymology/pathology ; Male ; Middle Aged ; Orotate Phosphoribosyltransferase/genetics/*metabolism ; Pancreas/enzymology/pathology ; Pancreatic Neoplasms/*enzymology/pathology ; Retrospective Studies ; }, abstract = {The purpose of this study was to clarify the role of orotate phosphoribosyltransferase (OPRT) in the progression of hepatobiliary and pancreatic carcinomas. Representative sections from 8 surgically resected pancreatic carcinomas, 5 gallbladder carcinomas and 19 hepatocellular carcinomas (HCCs) were examined microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma of the pancreas (IDC) were determined. Gallbladder carcinomas and HCCs were examined histologically, and the subtypes and spread patterns were assessed. Expression of OPRT was examined immunohistochemically. A total of 75 PanINs were identified. Expression of OPRT increased as lesions progressed from early to high-grade PanINs (PanIN-1A and -1B versus PanIN-2 and -3, p=0.0004). Three (37.5%) of the 8 pancreatic IDCs were positive for OPRT. In the remaining 5 cases, OPRT was expressed only in the neoplastic ducts adjacent to PanIN-3s. In gallbladder carcinomas, mucosal neoplastic epithelium showed dense cytoplasmic expression in 4 of the 5 cases, but expression was absent in the deeply invasive lesions. Among HCCs, 15 of the 19 cases were negative for OPRT in the central area of the tumor, but 8 of the 19 cases expressed OPRT in vascularly invasive lesions. Our data suggest that OPRT is involved in early events of pancreatic and gallbladder carcinogenesis and invasion of HCC.}, } @article {pmid17599361, year = {2007}, author = {Mirza, S and Sharma, G and Prasad, CP and Parshad, R and Srivastava, A and Gupta, SD and Ralhan, R}, title = {Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients.}, journal = {Life sciences}, volume = {81}, number = {4}, pages = {280-287}, doi = {10.1016/j.lfs.2007.05.012}, pmid = {17599361}, issn = {0024-3205}, mesh = {Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/*metabolism ; Biomarkers, Tumor/blood/genetics ; Breast Neoplasms/*blood/genetics/pathology ; CARD Signaling Adaptor Proteins ; Carcinoma, Ductal, Breast/*blood/genetics/pathology ; Cohort Studies ; Cytoskeletal Proteins/*metabolism ; DNA Methylation ; DNA, Neoplasm/*blood ; Epigenesis, Genetic ; Estrogen Receptor alpha/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Promoter Regions, Genetic/genetics ; Receptors, Progesterone/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Breast cancer is fast emerging as the leading cancer amongst females, especially in younger age group in India; a large proportion of these tumors are often aggressive and ER and/or PR negative. Promoter methylation of genes involved in DNA repair and hormonal regulation may, in part, account for this behavior. To test this hypothesis methylation status of tumor suppressor genes TMS1, BRCA1, ERalpha and PRB was determined in invasive ductal carcinoma of breast and paired serum DNA. Of the 50 breast cancer patients investigated, 36/50 (72%) tumors and 32/50 (64%) paired sera showed methylation of at least one of these genes, while 17/50 (34%) tumors and 12/50 (24%) sera showed methylation of three genes. Methylation frequencies ranged from 24% for TMS1 to 63% for ERalpha. Significant association was observed between ERalpha and PRB methylation (p< or =0.001) and there was concordance between DNA methylation in tumor and serum for each gene. Immunohistochemical analysis showed no detectable expression of ERalpha, PRB and BRCA1 in 21/36 (58%), 20/36 (56%) and 23/36 (64%) tumors respectively; significant correlation was observed between promoter methylation and loss of protein expression confirming our hypothesis that promoter methylation is an important mechanism for transcriptional silencing of these genes in breast cancer in this population. This study also underscores the potential utility of DNA methylation based screening of serum (a surrogate for tumor DNA methylation) as a tool for detection of breast cancer.}, } @article {pmid17597348, year = {2007}, author = {King, TA and Li, W and Brogi, E and Yee, CJ and Gemignani, ML and Olvera, N and Levine, DA and Norton, L and Robson, ME and Offit, K and Borgen, PI and Boyd, J}, title = {Heterogenic loss of the wild-type BRCA allele in human breast tumorigenesis.}, journal = {Annals of surgical oncology}, volume = {14}, number = {9}, pages = {2510-2518}, doi = {10.1245/s10434-007-9372-1}, pmid = {17597348}, issn = {1068-9265}, support = {R01 CA71840/CA/NCI NIH HHS/United States ; }, mesh = {*Alleles ; Breast Neoplasms/*genetics ; Female ; Gene Frequency ; *Genes, BRCA1 ; *Genes, BRCA2 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Haplotypes ; Humans ; *Loss of Heterozygosity ; Ovarian Neoplasms/genetics ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: For individuals genetically predisposed to breast and ovarian cancer through inheritance of a mutant BRCA allele, somatic loss of heterozygosity affecting the wild-type allele is considered obligatory for cancer initiation and/or progression. However, several lines of evidence suggest that phenotypic effects may result from BRCA haploinsufficiency.

METHODS: Archival fixed and embedded tissue specimens from women with germ line deleterious mutations in BRCA1 or BRCA2 were identified. After pathologic review, focal areas of normal breast epithelium, atypical ductal hyperplasia, ductal carcinoma-in-situ, and invasive ductal carcinoma were identified from 14 BRCA1-linked and 9 BRCA2-linked breast cancers. Ten BRCA-linked prophylactic mastectomy specimens and 12 BRCA-linked invasive ovarian carcinomas were also studied. Laser catapult microdissection was used to isolate cells from the various pathologic lesions and corresponding normal tissues. After DNA isolation, real-time polymerase chain reaction assays were used to quantitate the proportion of wild-type to mutant BRCA alleles in each tissue sample.

RESULTS: Quantitative allelotyping of microdissected cells revealed a high level of heterogeneity in loss of heterozygosity within and between preinvasive lesions and invasive cancers from BRCA1 and BRCA2 heterozygotes with breast cancer. In contrast, all BRCA-associated ovarian cancers displayed complete loss of the wild-type BRCA allele.

CONCLUSIONS: These data suggest that loss of the wild-type BRCA allele is not required for BRCA-linked breast tumorigenesis, which would have important implications for the genetic mechanism of BRCA tumor suppression and for the clinical management of this patient population.}, } @article {pmid17595678, year = {2007}, author = {Soederholm, A and Bánki, Z and Wilflingseder, D and Gassner, C and Zwirner, J and López-Trascasa, M and Falkensammer, B and Dierich, MP and Stoiber, H}, title = {HIV-1 induced generation of C5a attracts immature dendriticcells and promotes infection of autologous T cells.}, journal = {European journal of immunology}, volume = {37}, number = {8}, pages = {2156-2163}, doi = {10.1002/eji.200636820}, pmid = {17595678}, issn = {0014-2980}, mesh = {Chemotaxis, Leukocyte/*immunology ; Coculture Techniques ; Complement C5a/*immunology ; Dendritic Cells/immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; HIV Infections/*immunology ; HIV-1/*immunology/pathogenicity ; Humans ; T-Lymphocytes/immunology/*virology ; Transplantation, Autologous ; }, abstract = {For the recruitment of dendritic cells (DC) to the site of infection, DC express several sensors for danger signals, such as receptors for C5a. This anaphylatoxin is generated upon complement activation. As HIV-1 triggers the complement cascade, we determined whether C5a is generated by the virus and tested the functional activity of C5a in migration and infection assays. The immature (i)DC responded in migration assays to recombinant C5a and native C5a, which was generated in situ upon activation of the complement system by HIV-1. In combined migration and infection assays, a C5a-dependent enhancement of HIV-1 infection in DC-T cell cocultures was observed. These results indicate that HIV induces generation of C5a and thereby attracts iDC, which in turn promote the productive infection of autologous primary T cells.}, } @article {pmid17595076, year = {2007}, author = {Gu, JZ and Lu, WG and Jiang, L and Zhou, HC and Lu, TB}, title = {3D porous metal-organic framework exhibiting selective adsorption of water over organic solvents.}, journal = {Inorganic chemistry}, volume = {46}, number = {15}, pages = {5835-5837}, doi = {10.1021/ic7004908}, pmid = {17595076}, issn = {0020-1669}, mesh = {Adsorption ; Chemical Phenomena ; Chemistry, Organic/*methods ; Chemistry, Physical ; Crystallization ; Ions ; Ligands ; Metals/*chemistry ; Models, Chemical ; Molecular Conformation ; Solvents ; Water/*chemistry ; X-Ray Diffraction ; Zinc/chemistry ; }, abstract = {A 3D porous metal-organic framework (MOF) with 1D open channels has been constructed hydrothermally using Zn(II) and a rigid planar ligand IDC(3)- (imidazole-4,5-dicarboxylate). This MOF can adsorb water selectively over organic solvents and can be regenerated and reused. It also represents a rare example of a MOF with open channels that form/collapse reversibly upon hydration/dehydration.}, } @article {pmid17594124, year = {2007}, author = {Belluco, C and Petricoin, EF and Mammano, E and Facchiano, F and Ross-Rucker, S and Nitti, D and Di Maggio, C and Liu, C and Lise, M and Liotta, LA and Whiteley, G}, title = {Serum proteomic analysis identifies a highly sensitive and specific discriminatory pattern in stage 1 breast cancer.}, journal = {Annals of surgical oncology}, volume = {14}, number = {9}, pages = {2470-2476}, doi = {10.1245/s10434-007-9354-3}, pmid = {17594124}, issn = {1068-9265}, support = {N01-CO-12400/CO/NCI NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood ; Breast Neoplasms/*blood/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Proteins/*blood ; Neoplasm Staging ; Proteomics/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {BACKGROUND: Mass spectrometry (MS)-based profiling was used to determine whether ion fingerprints could distinguish women with stage 1 breast cancer from women without breast cancer.

METHODS: The initial study population consisted of 310 subjects: 155 women with yearly negative breast examination and negative mammography findings for at least 4 years, and 155 women undergoing surgery for pathology-proven stage 1 invasive ductal carcinoma. High-resolution SELDI-TOF (surface-enhanced laser desorption ionization-time of flight) analysis was performed on serum obtained from blood samples collected before mammography in controls, and before surgery in patients with breast cancer. Samples were divided into a training (109 controls and 109 cancers) and blinded (46 controls and 46 cancers) testing set; each group had similar age demographics. In addition, an independent study set of 46 serum samples was analyzed 14 months after the initial study to validate the robustness of the classifier.

RESULTS: A discriminatory profile consisting of seven ion peaks found in the training set, when applied to the blinded test set, achieved a sensitivity and specificity of 95.6% and 86.5%, respectively. This same seven-peak profile achieved a 96.5% sensitivity and 85.7% specificity, with correct identification of all of 17 T1a tumors when applied to the validation study set.

CONCLUSIONS: Mass spectrometry profiling of human serum generated a robust classifier composed of seven low-molecular-weight ions that yielded a highly sensitive and specific diagnostic procedure for the discrimination of women with stage 1 breast cancer compared with women without breast cancer in this research study set.}, } @article {pmid17593051, year = {2007}, author = {Beresford, M and Lyburn, I and Sanghera, B and Makris, A and Wong, WL}, title = {Serial integrated (18)F-fluorodeoxythymidine PET/CT monitoring neoadjuvant chemotherapeutic response in invasive ductal carcinoma.}, journal = {The breast journal}, volume = {13}, number = {4}, pages = {424-425}, doi = {10.1111/j.1524-4741.2007.00454.x}, pmid = {17593051}, issn = {1075-122X}, mesh = {Antibiotics, Antineoplastic/adverse effects ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/diagnosis/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*drug therapy/*pathology ; Cyclophosphamide/adverse effects ; *Dideoxynucleosides ; Drug Monitoring/*methods ; Epirubicin/administration & dosage ; Female ; Fluorine Radioisotopes ; Fluorouracil/administration & dosage ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Neoplasm Invasiveness ; *Positron-Emission Tomography ; *Tomography, X-Ray Computed ; }, } @article {pmid17593048, year = {2007}, author = {Cheung, KJ and Tam, W and Chuang, E and Osborne, MP}, title = {Concurrent invasive ductal carcinoma and chronic lymphocytic leukemia manifesting as a collision tumor in breast.}, journal = {The breast journal}, volume = {13}, number = {4}, pages = {413-417}, doi = {10.1111/j.1524-4741.2007.00451.x}, pmid = {17593048}, issn = {1075-122X}, mesh = {Breast Neoplasms/*pathology/radiotherapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/radiotherapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*pathology/radiotherapy ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Lymphoma/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*pathology ; Sentinel Lymph Node Biopsy ; }, abstract = {Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement in the same site. The occurrence of these tumors in the breast is extremely rare. Here, we present a case of a patient with both invasive ductal carcinoma and chronic lymphocytic leukemia in the breast. Wide excision with sentinel lymph node biopsy revealed palpably abnormal lymph nodes negative for breast carcinoma on frozen section. Histopathological examination of these lymph nodes showed extensive involvement by lymphoma and review of the breast specimen demonstrated the same lymphoma at the periphery of the ductal carcinoma. We review the literature and discuss possible etiologies for the dual presentation of both cancers.}, } @article {pmid17590131, year = {2007}, author = {Sánchez Muñoz, LA and Castiella Herrero, J and Sanjuán Portugal, FJ and Naya Manchado, J and Alfaro Alfaro, MJ}, title = {[Usefulness of MBDS in detection of adverse drug events].}, journal = {Anales de medicina interna (Madrid, Spain : 1984)}, volume = {24}, number = {3}, pages = {113-119}, doi = {10.4321/s0212-71992007000300003}, pmid = {17590131}, issn = {0212-7199}, mesh = {Adult ; *Adverse Drug Reaction Reporting Systems ; Aged ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Spain ; }, abstract = {OBJECTIVE: To analyze the incidence of adverse drug events (ADE) as noted in hospital discharge reports, as well as their potential avoidability, drugs involved, clinical symptoms and the type of medication errors that led to the preventable ADE.

MATERIAL AND METHODS: A retrospective study for the January- December 2005 period of time, at a district hospital. ADE were detected in which patients with discharge reports including event codes as defined by the IDC-9-CM system, using the minimum basic data set (MBDS).

RESULTS: ADEs were detected in 4.01% of all discharge reports in the study period (n = 160). 45% of ADEs were were detected at the Emergency Department (n = 72) and 55% (n = 88) were detected during hospitalization.62.3% of ADEs were considered potentially avoidable (n = 109). 38.1% of ADEs were serious, 40.0% moderate and 21.9% mild. Drugs most commonly involved in the ADEs sample studied included: antimicrobials (24.0%), systemic corticoids (15.4%), NSAIDs (11.4%), diuretics (10.3%), digoxin (9.1%), insulin and oral hypoglycaemic agents (5.7%), anticoagulants and heparin (5.7%). Inadequate therapy monitoring (47.7%), excessive dosage (28.5%), drug-drug interactions (10.1%) were the most common identified type of errors leading to preventable ADE.

CONCLUSIONS: 3.2% of admissions was caused by ADEs. 2.2% of hospitalized patients experienced ADEs. 62% of ADEs were potentially preventable. A high proportion of preventable ADEs were around a small number of drugs. Effective safety practices directed to reduce the incidence of medication errors are needed.}, } @article {pmid17587091, year = {2007}, author = {Black, D and Specht, M and Lee, JM and Dominguez, F and Gadd, M and Hughes, K and Rafferty, E and Smith, B}, title = {Detecting occult malignancy in prophylactic mastectomy: preoperative MRI versus sentinel lymph node biopsy.}, journal = {Annals of surgical oncology}, volume = {14}, number = {9}, pages = {2477-2484}, doi = {10.1245/s10434-007-9356-1}, pmid = {17587091}, issn = {1068-9265}, mesh = {Adult ; Axilla ; Breast Neoplasms/*diagnosis/genetics/pathology/surgery ; Costs and Cost Analysis ; Diagnostic Errors/economics ; Female ; Genetic Predisposition to Disease ; Humans ; Intraoperative Care/economics ; Lymph Node Excision ; Lymphatic Metastasis ; Magnetic Resonance Imaging/economics/*methods ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Preoperative Care/economics ; Primary Prevention ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; *Sentinel Lymph Node Biopsy/economics ; }, abstract = {BACKGROUND: High-risk patients undergoing prophylactic mastectomy (PM) may have unsuspected cancers identified on pathology. The optimum way to identify and manage them is controversial. Magnetic resonance imaging (MRI) may identify occult cancer preoperatively. Sentinel lymph node biopsy (SLNB) allows intraoperative staging and axillary dissection during the same operation. We determined the efficacy and cost of MRI and/or SLNB in managing high-risk PM patients.

METHODS: We reviewed 192 PMs in 173 patients from 1999 to 2005. Costs were estimated for MRI and SLNB during PM by the 2005 Medicare Resource-Based Relative Value Scale. We also estimated costs and procedures for the four strategies in a larger hypothetical cohort.

RESULTS: A total of 19 (10%) of 192 PMs contained occult cancers, 14 ductal carcinoma-in-situ (DCIS) and 5 invasive ductal carcinoma (IDC). In 59 patients, MRI detected an IDC but missed two DCIS and an IDC. Positive MRIs generated an additional average cost of $1,207 per patient. In 56 PMs with SLNB, 6 occult cancers were found, 5 DCIS and 1 IDC, all with negative SLNBs. Adding a SLNB costs an additional average of $644. A theoretical analysis demonstrated that PM alone costs $808 per patient, PM with SLNB costs $1,420, PM with MRI and selective SLNB costs $1,774, and PM with routine MRI and SLNB costs $2,379.

CONCLUSIONS: MRI adds great cost and misses most occult cancers in PMs. SLNB allows the rare patient with occult IDC to avoid axillary dissection but adds cost. Given the low rate of unsuspected invasive cancers and the costs of MRI and SLNB, neither is recommended as standard practice for PM patients.}, } @article {pmid17581710, year = {2007}, author = {Yoshikawa, MI and Ohsumi, S and Sugata, S and Kataoka, M and Takashima, S and Kikuchi, K and Mochizuki, T}, title = {Comparison of breast cancer detection by diffusion-weighted magnetic resonance imaging and mammography.}, journal = {Radiation medicine}, volume = {25}, number = {5}, pages = {218-223}, pmid = {17581710}, issn = {0288-2043}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/diagnostic imaging/pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; }, abstract = {PURPOSE: Breast cancer-detecting ability of diffusion-weighted magnetic resonance imaging (DW-MRI) was investigated by comparing the breast cancer detection rates of DW-MRI and mammography (MMG).

MATERIALS AND METHODS: The subjects were 48 women who had breast cancer (53 cancer lesions) who underwent DW-MRI before surgery. Altogether, 41 lesions were invasive ductal carcinoma (IDC), 7 were noninvasive ductal carcinoma (NIDC) and 5 were "others."

RESULTS: The breast cancer detection rates by MMG and DW-MRI were 84.9% and 94.3% (P < 0.001), respectively. In each classification of histology and size, the detection rate by DW-MRI was higher than that by MMG. In relation to the mammary gland density, the detection rates of fatty, scattered, heterogeneously dense, and extremely dense mammary glands were 100%, 100%, 92.0%, and 83.3%, respectively. The mean apparent diffusion coefficient values of the histologic types were 1.07 +/- 0.17 x 10(-3), 1.50 +/- 0.24 x 10(-3), 1.12 +/- 0.25 x 10(-3), and 2.01 +/- 0.29 x 10(-3) mm(2)/s for IDC, NIDC, others, and normal breast, respectively, showing that the values of IDC and NIDC were significantly different from that of the normal breast (P < 0.001 each). A significant difference was also noted between IDC and NIDC (P < 0.001).

CONCLUSION: DW-MRI may be useful for detecting breast cancer in a wide age group of women, including young women with dense mammary glands.}, } @article {pmid17576158, year = {2007}, author = {Breckpot, K and Emeagi, P and Dullaers, M and Michiels, A and Heirman, C and Thielemans, K}, title = {Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors.}, journal = {Human gene therapy}, volume = {18}, number = {6}, pages = {536-546}, doi = {10.1089/hum.2007.006}, pmid = {17576158}, issn = {1043-0342}, mesh = {Cell Adhesion ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Flow Cytometry ; *Gene Transfer Techniques ; Genetic Vectors ; Humans ; Lentivirus/*genetics ; Monocytes/*immunology ; Phenotype ; Toll-Like Receptors/genetics/metabolism ; *Transduction, Genetic ; eIF-2 Kinase/genetics/metabolism ; }, abstract = {Dendritic cells (DCs) are an attractive tool for immunomodulation, targeting mature DCs (mDCs) for immunization or immature/semimature DCs (iDCs) for tolerization. Therefore, introducing antigens into DCs has become a prime topic in various immunological disciplines. Numerous studies have shown that lentiviruses are an efficient vehicle for this purpose. This study evaluates the effects of lentiviral transduction on iDC activation. Immature DCs are efficiently transduced with increasing doses of lentivirus without affecting cell viability. Transduction at low multiplicities of infection (MOIs) did not result in phenotypical or functional maturation. Higher doses of lentivirus, however, resulted in upregulation of adhesion, costimulatory, and HLA molecules, as well as in increased allostimulatory capacity and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha. Production of IL-12 p70, IL-10, and interferon-alpha was observed only at extremely high doses. Protein kinase R phosphorylation on transduction at an MOI of 150 was demonstrated by Western blotting. A Toll-like receptor (TLR)-driven luciferase reporter assay showed dose-dependent activation of TLR2, TLR3, and TLR8, which was independent of the pseudotype, production, or transduction protocol and was abrogated on heat inactivation. These data show that lentiviral vectors provide not only the antigen but also appropriate activation signals to iDCs, favoring their use for immunotherapy and vaccine development.}, } @article {pmid17568853, year = {2006}, author = {Dos Reis, FJ and de Sousa, TA and Oliveira, MS and Dantas, N and Silveira, M and Braghiroly, MI and Paraná, R}, title = {Is hepatitis C virus a cause of idiopathic dilated cardiomyopathy? A systematic review of literature.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {10}, number = {3}, pages = {199-202}, doi = {10.1590/s1413-86702006000300009}, pmid = {17568853}, issn = {1413-8670}, mesh = {Cardiomyopathy, Dilated/*virology ; Hepatitis C/*complications ; Humans ; }, abstract = {Recent studies have suggested that some patients with idiopathic dilated cardiomyopathy (IDC) are also afflicted with insidious forms of viral myocarditis. Participation of hepatitis C virus (HCV) in this process has been postulated. The objective of this study was to evaluate a possible association between hepatitis C virus and idiopathic dilated cardiomyopathy. Systematic review of the literature using electronic databases (MEDLINE, EMBASES, LILACS and COCHRANE) for the period from 1995 to 2005, limited to papers published in English, Spanish and Portuguese. Sixty-two papers were found, of which six were in accordance with the proposed methodology. After selection, the articles were classified by quality of data and number of variables studied. Most of the patients were male adults from 31 and 75 years old, who had ischemic cardiopathy excluded as etiology of the dilated cardiomyopathy. A significant association between dilated cardiomyopathy and hepatitis C virus was found in only two papers, both from Japan and by the same author. Most of the papers received low classifications, as they did not fulfill the systematization criteria.}, } @article {pmid17567699, year = {2007}, author = {Wang, JH and Janas, AM and Olson, WJ and Wu, L}, title = {Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells.}, journal = {Journal of virology}, volume = {81}, number = {17}, pages = {8933-8943}, pmid = {17567699}, issn = {0022-538X}, support = {R01 AI068493/AI/NIAID NIH HHS/United States ; R01 AI068493-02/AI/NIAID NIH HHS/United States ; }, mesh = {Cells, Cultured ; Dendritic Cells/immunology/ultrastructure/*virology ; Endocytosis ; HIV-1/*growth & development/physiology ; Humans ; Lectins, C-Type/physiology ; Microscopy, Electron, Transmission ; Virus Internalization ; }, abstract = {Dendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear. Here we have compared monocyte-derived iDCs and mDCs for their efficiencies and mechanisms of HIV-1 transmission. We have found that mDCs significantly facilitate HIV-1 endocytosis and efficiently concentrate HIV-1 at virological synapses, which contributes to mDC-enhanced viral transmission, at least in part. mDCs were more efficient than iDCs in transferring HIV-1 to various types of target cells independently of C-type lectins, which partially accounted for iDC-mediated HIV-1 transmission. Efficient HIV-1 trans-infection mediated by iDCs and mDCs required contact between DCs and target cells. Moreover, rapid HIV-1 degradation occurred in both iDCs and mDCs, which correlated with the lack of HIV-1 retention-mediated long-term viral transmission. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission, suggesting that HIV-1 exploits mDCs to facilitate its dissemination within lymphoid tissues.}, } @article {pmid17557561, year = {2007}, author = {Piccirilli, M and Sassun, TE and Brogna, C and Giangaspero, F and Salvati, M}, title = {Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.}, journal = {Tumori}, volume = {93}, number = {2}, pages = {150-154}, doi = {10.1177/030089160709300207}, pmid = {17557561}, issn = {0300-8916}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Aged ; Brain Neoplasms/mortality/*secondary/*therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Cranial Irradiation ; Female ; Humans ; Middle Aged ; Palliative Care ; Radiosurgery ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; }, abstract = {AIMS AND BACKGROUND: Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor.

PATIENTS AND METHODS: Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30).

RESULTS: Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years).

CONCLUSIONS: Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.}, } @article {pmid17554196, year = {2007}, author = {Kim, MJ and Kim, EK and Lee, JY and Youk, JH and Park, BW and Kim, H and Oh, KK}, title = {Breast cancer from the excisional scar of a benign mass.}, journal = {Korean journal of radiology}, volume = {8}, number = {3}, pages = {254-257}, pmid = {17554196}, issn = {1229-6929}, mesh = {Breast Neoplasms/*etiology/pathology/surgery ; Carcinoma, Ductal, Breast/*etiology ; Cicatrix/*complications ; Female ; Foreign-Body Reaction/pathology ; Giant Cells/pathology ; Humans ; Middle Aged ; Papilloma, Intraductal/pathology/surgery ; }, abstract = {Breast cancer developing from a surgical scar is rare; this type of malignancy has been reported in only 12 cases to date. Herein, we report on a 52-year-old female who developed infiltrating ductal carcinoma in a surgical scar following excision of a benign mass. Two years previously, the patient underwent surgery and radiotherapy for invasive ductal carcinoma of the contralateral breast. The initial appearance of the scar was similar to fat necrosis; it was observed to be progressively shrinking on follow-up sonography. On the two year follow-up ultrasound, the appearance changed, an angular margin and vascularity at the periphery of the scar were noted. A biopsy and subsequent excision of the scar were performed; the diagnosis of infiltrating ductal carcinoma of the scar was confirmed.}, } @article {pmid17549359, year = {2007}, author = {Park, SS and Kim, SW}, title = {Activated Akt signaling pathway in invasive ductal carcinoma of the breast: correlation with HER2 overexpression.}, journal = {Oncology reports}, volume = {18}, number = {1}, pages = {139-143}, pmid = {17549359}, issn = {1021-335X}, mesh = {Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/*metabolism ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; *Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Akt/PKB is a serine/threonine kinase that plays a crucial role in cell survival and apoptosis. Aberrant activation of pAkt is associated with various malignant human cancers, including breast carcinoma. In vitro studies show that pAkt activation is mediated by estrogen and acts as a downstream effector of HER2 with implications in breast cancer progression and drug resistance. We investigated the incidence of Akt activation in invasive ductal carcinoma and its correlation with other clinicopathological variables. Using tissue microarray technology, immunohistochemical expression of phosphorylated Akt (pAkt) at Ser-473 was evaluated in 127 cases of invasive ductal carcinomas, together with hormone receptors, HER2, p53, Ki-67 and other clinicopathological variables. Both nuclear and cytoplasmic expression was noted for pAkt, with 46 cases (36.2%) showing high cytoplasmic pAkt expression and 37 cases (29.1%) showing high nuclear pAkt expression. There was a significant association between both high cytoplasmic and nuclear pAkt expression with HER2 overexpression (both p<0.0001). There was also a positive correlation between high nuclear pAkt expression with both estrogen receptor and progesterone receptor status (p=0.042 and p=0.015, respectively). High cytoplasmic pAkt expression was associated with high Ki-67 expression (p=0.052), however, there was no association between pAkt and p53 expression. In the present study, activation of the Akt pathway shows strong association with HER2 overexpression, which is consistent with many in vitro studies. Our study also showed a positive correlation between pAkt and hormone receptors, which suggested the possible mechanism of endocrine resistance in ER-positive breast cancer. These results also suggest the prognostic value of pAkt and its importance in the prediction of therapeutic response in invasive ductal carcinoma of the breast.}, } @article {pmid17540213, year = {2007}, author = {Sugioka, K and Hozumi, T and Takemoto, Y and Ehara, S and Ogawa, K and Iwata, S and Oe, H and Matsumura, Y and Otsuka, R and Yoshiyama, M and Yoshikawa, J}, title = {Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {153}, number = {6}, pages = {1080.e1-6}, doi = {10.1016/j.ahj.2007.03.014}, pmid = {17540213}, issn = {1097-6744}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Blood Flow Velocity ; Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/*complications/diagnostic imaging/*drug therapy ; Carvedilol ; Coronary Vessels/diagnostic imaging ; Echocardiography ; Female ; Follow-Up Studies ; Fractional Flow Reserve, Myocardial/*drug effects ; Humans ; Male ; Middle Aged ; Propanolamines/*therapeutic use ; Stroke Volume/*drug effects ; Ventricular Dysfunction, Left/etiology/*prevention & control ; }, abstract = {BACKGROUND: Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in these circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in patients with IDC.

METHODS: Eighteen patients with IDC underwent CFR measurements by transthoracic Doppler echocardiography at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 +/- 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as group A (LVEF change > or = 10%) and group B (LVEF change < 10%).

RESULTS: Although there was no significant difference in CFR between the 2 groups at baseline, CFR was significantly higher in group A than in group B at 1 month of therapy (3.7 +/- 0.5 vs 2.5 +/- 0.9; P < .01). Coronary flow reserve change after 1 month was significantly greater in group A than in group B (1.3 +/- 0.6 vs 0.4 +/- 0.5; P < .01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up (P < .05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r = 0.65, P < .01).

CONCLUSIONS: This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.}, } @article {pmid17532057, year = {2007}, author = {Yao, Q and Doan, LX and Zhang, R and Bharadwaj, U and Li, M and Chen, C}, title = {Thymosin-alpha1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes.}, journal = {Immunology letters}, volume = {110}, number = {2}, pages = {110-120}, pmid = {17532057}, issn = {0165-2478}, support = {R01 HL083471/HL/NHLBI NIH HHS/United States ; R21 AT003094-02/AT/NCCIH NIH HHS/United States ; EB-002436/EB/NIBIB NIH HHS/United States ; R01 EB002436/EB/NIBIB NIH HHS/United States ; R01 HL072716/HL/NHLBI NIH HHS/United States ; R01 DE015543-04/DE/NIDCR NIH HHS/United States ; HL083471/HL/NHLBI NIH HHS/United States ; R01 DE015543/DE/NIDCR NIH HHS/United States ; R01 HL065916/HL/NHLBI NIH HHS/United States ; AT003094/AT/NCCIH NIH HHS/United States ; R21 AT003094/AT/NCCIH NIH HHS/United States ; DE15543/DE/NIDCR NIH HHS/United States ; HL65916/HL/NHLBI NIH HHS/United States ; HL72716/HL/NHLBI NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic ; Cell Differentiation ; Cytokines/*immunology/metabolism ; Dendritic Cells/cytology/*immunology/metabolism ; Flow Cytometry ; Humans ; *Lipopolysaccharide Receptors/blood/immunology ; Lymphocyte Culture Test, Mixed ; Monocytes/cytology/*immunology/metabolism ; T-Lymphocytes/*immunology/metabolism ; Thymalfasin ; Thymosin/*analogs & derivatives/immunology/metabolism ; }, abstract = {Although thymosins have been demonstrated to have immunomodulatory effects, it is still not clear whether they could affect dendritic cells (DCs), the most professional antigen-presenting cells. The objective of this study was to determine the effect and potential mechanisms of thymosin-alpha1 (Talpha1) on DC differentiation and functional maturation. Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs). In the presence of Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis. However, Tbeta4 or Tbeta10 did not show these effects on iDCs. There was an approximately 30% reduction in antigen (FITC-conjugated dextran)-uptake by Talpha1-treated iDCs as compared with non-Talpha1-treated iDCs. In addition, Talpha1-treated matured DCs (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation as measured by a mixed-lymphocyte reaction assay. Talpha1-treated mDCs also increased the production of several Th1- and Th2-type cytokines as measured by a Bio-Plex cytokine assay. Furthermore, rapid activation of p38 MAPK and NFkappaB was seen in Talpha1-treated iDCs as measured by a Bio-Plex phosphoprotein assay. Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways. This study provides a basis to further evaluate Talpha1 as a possible adjuvant for a DC-directed vaccine or therapy.}, } @article {pmid17525722, year = {2007}, author = {Smits, EL and Ponsaerts, P and Van de Velde, AL and Van Driessche, A and Cools, N and Lenjou, M and Nijs, G and Van Bockstaele, DR and Berneman, ZN and Van Tendeloo, VF}, title = {Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells.}, journal = {Leukemia}, volume = {21}, number = {8}, pages = {1691-1699}, doi = {10.1038/sj.leu.2404763}, pmid = {17525722}, issn = {0887-6924}, mesh = {Acute Disease ; Cells, Cultured ; Coculture Techniques ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Electroporation ; Flow Cytometry ; Humans ; Interferon Type I/immunology ; Interferon-gamma/immunology ; Leukemia, Myeloid/*genetics/immunology/pathology ; Lymphocyte Activation ; Poly I-C/metabolism ; RNA, Double-Stranded/*genetics ; T-Lymphocytes/*immunology ; Th1 Cells/immunology ; Toll-Like Receptor 3/genetics/*metabolism ; *Transfection ; }, abstract = {Leukemic cells exert immunosuppressive effects that interfere with dendritic cell (DC) function and hamper effective antileukemic immune responses. Here, we sought to enhance the immunogenicity of leukemic cells by loading them with the double-stranded (ds) RNA Toll-like receptor 3 (TLR3) ligand polyriboinosinic polyribocytidylic acid (poly(I:C)), mimicking viral infection of the tumor cells. Given the responsiveness of DC to TLR ligands, we hypothesized that the uptake of poly(I:C)-loaded leukemic cells by immature DC (iDC) would lead to DC activation. Primary acute myeloid leukemia (AML) cells and AML cell lines markedly responded to poly(I:C) electroporation by apoptosis, upregulation of TLR3 expression, enhanced expression of major histocompatibility complex (MHC) and costimulatory molecules and by production of type I interferons (IFN). Upon phagocytosis of poly(I:C)-electroporated AML cells, DC maturation and activation were induced as judged by an increased expression of MHC and costimulatory molecules, production of proinflammatory cytokines and an increase of T helper 1 (T(H)1)-polarizing capacity. These immune effects were suboptimal when AML cells were passively pulsed with poly(I:C), indicating the superiority of poly(I:C) transfection over pulsing. Our results demonstrate that poly(I:C) electroporation is a promising strategy to increase the immunogenicity of AML cells and to convert iDC into activated mature DC following the phagocytosis of AML cells.}, } @article {pmid17522367, year = {2007}, author = {Steinman, S and Wang, J and Bourne, P and Yang, Q and Tang, P}, title = {Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast.}, journal = {Annals of clinical and laboratory science}, volume = {37}, number = {2}, pages = {127-134}, pmid = {17522367}, issn = {0091-7370}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; ErbB Receptors/metabolism ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Immunohistochemistry ; Keratins/metabolism ; Neoplasms, Multiple Primary ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can be divided into 3 subtypes (luminal, basal/stem, and null) based on the expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and CK8, CK18 (luminal). The distributions of CK subtypes were associated with nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (EGFR). In this study, we further explore the expression patterns of CK markers, ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99 cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there are differential expression patterns for ER-alpha, PR, and EGFR in corresponding CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from DCIS/IDC. In most cases there is a high degree of co-expression of these markers between DCIS and the co-existing IDC, suggesting that DCIS is frequently a precursor lesion for co-existing IDC. The rate of discordant expression of these markers is low and is more frequently associated with high-grade carcinoma, suggesting that other molecular pathways also may also be present. There are significant differences in the expression of these molecular markers between high-grade and non-high-grade carcinomas, supporting the view that high-grade and non-high-grade carcinomas of the breast are molecularly distinct entities.}, } @article {pmid17520201, year = {2007}, author = {Inagaki, M and Obara, M and Kino, S and Goto, J and Suzuki, S and Ishizaki, A and Tanno, S and Kohgo, Y and Tokusashi, Y and Miyokawa, N and Kasai, S}, title = {Pylorus-preserving total pancreatectomy for an intraductal papillary-mucinous neoplasm of the pancreas.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {14}, number = {3}, pages = {264-269}, doi = {10.1007/s00534-006-1146-9}, pmid = {17520201}, issn = {0944-1166}, mesh = {Adenocarcinoma, Mucinous/diagnosis/*surgery ; Adenocarcinoma, Papillary/diagnosis/*surgery ; Aged ; Carcinoma, Pancreatic Ductal/diagnosis/*surgery ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangiopancreatography, Magnetic Resonance ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pancreatectomy/*methods ; Pancreatic Neoplasms/diagnosis/*surgery ; Pylorus/*surgery ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {BACKGROUND/PURPOSE: Total pancreatectomy (TP) is rarely performed to treat invasive ductal carcinoma of the pancreas, due to the associated markedly impaired quality of life and poor prognosis after the resection. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is characterized by extensive intraductal spread and a favorable outcome even when presenting at an invasive stage. We herein reappraise the role of pylorus-preserving total pancreatectomy (PPTP) as a viable alternative pancreatic resection modality for borderline and malignant IPMN.

METHODS: A total of five patients with IPMN underwent PPTP and their clinical follow-up data were reviewed.

RESULTS: TP was performed due to recurrent IPMN in the remnant pancreas after distal pancreatectomy in three patients and due to massive involvement of the entire pancreas in the others. All patients were treated by the pylorus-preserving method, while the spleen was also preserved in one patient. The surgical margins were negative and no metastasis to the resected lymph nodes was evident, based on histological examinations. One patient underwent a re-operation due to postoperative intraabdominal bleeding, while another patient required tubedrainage for left pleural effusion. Three of the four patients who underwent PPTP with a splenectomy experienced postoperative gastric ulcer, which were controlled by medication. One patient died due to suicide 16 months after the PPTP. All the others were doing well without recurrence at periods of 62 to 127 months after the PPTP.

CONCLUSIONS: PPTP is therefore considered to be indicated as an effective treatment for borderline or malignant IPMN with extensive involvement, when the patient's condition permits, in order to achieve complete resection of the IPMN.}, } @article {pmid17520199, year = {2007}, author = {Nagata, K and Horinouchi, M and Saitou, M and Higashi, M and Nomoto, M and Goto, M and Yonezawa, S}, title = {Mucin expression profile in pancreatic cancer and the precursor lesions.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {14}, number = {3}, pages = {243-254}, doi = {10.1007/s00534-006-1169-2}, pmid = {17520199}, issn = {0944-1166}, mesh = {Adenocarcinoma, Mucinous/genetics/*metabolism/pathology ; Biomarkers, Tumor/biosynthesis/genetics ; DNA, Neoplasm/*genetics ; *Gene Expression Regulation, Neoplastic ; Humans ; Mucins/biosynthesis/*genetics ; Pancreatic Neoplasms/genetics/*metabolism/pathology ; Precancerous Conditions/genetics/*metabolism/pathology ; }, abstract = {In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary-mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.}, } @article {pmid17516241, year = {2007}, author = {Cejas, P and García-Cabezas, MA and Casado, E and Belda-Iniesta, C and De Castro, J and Fresno, JA and Sereno, M and Barriuso, J and Espinosa, E and Zamora, P and Feliu, J and Redondo, A and Hardisson, DA and Renart, J and González-Barón, M}, title = {Phospholipid hydroperoxide glutathione peroxidase (PHGPx) expression is downregulated in poorly differentiated breast invasive ductal carcinoma.}, journal = {Free radical research}, volume = {41}, number = {6}, pages = {681-687}, doi = {10.1080/10715760701286167}, pmid = {17516241}, issn = {1071-5762}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/genetics/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/pathology ; *Cell Differentiation ; Down-Regulation ; Female ; *Gene Expression Regulation, Enzymologic ; Glutathione Peroxidase/genetics/*metabolism ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Phospholipid Hydroperoxide Glutathione Peroxidase ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has been involved in apoptosis and can influence intracellular signaling. To investigate the possible relationship between PHGPx and human cancer we have quantified PHGPx expression levels by real-time quantitative PCR and immunohistochemistry in tissue samples of human breast invasive ductal carcinoma from 34 patients compared with their own controls of benign breast tissue. PHGPx expression levels were compared with the clinical and pathological data of these patients. The results showed that PHGPx expression levels are downregulated in poorly differentiated (grade 3) breast invasive ductal carcinoma (P = 0.0043). PHGPx expression levels decreased gradually with tumor grade from grade 1 to grade 3. We also found a downregulation of PHGPx in cases that showed p53 accumulation compared with cases without p53 immunostaining (P = 0.0011). PHGPx was also downregulated in cases without progesterone receptors (PR) immunostaining compared with cases with PR immunostaining (P = 0.0165). Grade 3, p53 immunostaining and absence of PR immunostaining are poor prognostic factors. These results suggest that PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma.}, } @article {pmid17513187, year = {2007}, author = {van Esser, S and Veldhuis, WB and van Hillegersberg, R and van Diest, PJ and Stapper, G and ElOuamari, M and Borel Rinkes, IH and Mali, WP and van den Bosch, MA}, title = {Accuracy of contrast-enhanced breast ultrasound for pre-operative tumor size assessment in patients diagnosed with invasive ductal carcinoma of the breast.}, journal = {Cancer imaging : the official publication of the International Cancer Imaging Society}, volume = {7}, number = {1}, pages = {63-68}, pmid = {17513187}, issn = {1470-7330}, mesh = {Adult ; Breast Neoplasms/*diagnostic imaging/surgery ; Carcinoma, Ductal, Breast/*diagnostic imaging/surgery ; Female ; Humans ; Middle Aged ; *Phospholipids ; Preoperative Care/methods ; Prospective Studies ; Sensitivity and Specificity ; *Sulfur Hexafluoride ; Ultrasonography ; }, abstract = {Our aim was to assess the feasibility and accuracy of contrast-enhanced ultrasound (CEUS) of the breast with SonoVue microbubbles for pre-operative size measurement of invasive breast carcinomas. Seven patients diagnosed with nine invasive breast carcinomas prospectively underwent gray-scale ultrasound and CEUS of the breast according to a standardized protocol. CEUS of the breast was performed by a Philips iU22 scanner equipped with a 4-8 MHz linear array transducer. We used a single dose of 2.4 ml SonoVue as contrast agent. Breast lesion morphology was scored according to the sonographic BI-RADS lexicon criteria and classified accordingly. The greatest tumor dimensions on gray-scale ultrasound and CEUS of the breast were finally compared with the greatest histopathologic tumor sizes. Gray-scale ultrasound underestimated the histopathologic tumor size in 6/9 cases (67%), whereas CEUS of the breast underestimated tumor size in only 3/9 (33%) cases. CEUS of the breast was significantly more accurate for tumor size assessment. Greatest tumor dimension as measured with gray-scale ultrasound of the breast was within 2 mm of the pathologic tumor size in only 2/9 cases (22%), whereas CEUS of the breast accurately assessed tumor size within 2 mm of pathologic tumor size in 6/9 (67%) of the cases (P<0.05). CEUS of the breast proved to be a feasible and safe procedure. It is more accurate than gray-scale ultrasound of the breast for pre-operative size assessment of invasive ductal breast carcinomas.}, } @article {pmid17512128, year = {2007}, author = {Sanlioglu, AD and Korcum, AF and Pestereli, E and Erdogan, G and Karaveli, S and Savas, B and Griffith, TS and Sanlioglu, S}, title = {TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.}, journal = {International journal of radiation oncology, biology, physics}, volume = {69}, number = {3}, pages = {716-723}, doi = {10.1016/j.ijrobp.2007.03.057}, pmid = {17512128}, issn = {0360-3016}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma, Ductal, Breast/*chemistry/mortality/pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/*analysis ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Receptors, TNF-Related Apoptosis-Inducing Ligand/*analysis ; Receptors, Tumor Necrosis Factor, Member 10c/analysis ; TNF-Related Apoptosis-Inducing Ligand/*analysis ; }, abstract = {PURPOSE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration.

METHODS AND MATERIALS: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns.

RESULTS: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions.

CONCLUSIONS: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.}, } @article {pmid17507722, year = {2007}, author = {Yang, SK and Moon, WK and Cho, N and Park, JS and Cha, JH and Kim, SM and Kim, SJ and Im, JG}, title = {Screening mammography-detected cancers: sensitivity of a computer-aided detection system applied to full-field digital mammograms.}, journal = {Radiology}, volume = {244}, number = {1}, pages = {104-111}, doi = {10.1148/radiol.2441060756}, pmid = {17507722}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/pathology ; Chi-Square Distribution ; Diagnosis, Differential ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; *Mammography ; Middle Aged ; Radiographic Image Enhancement ; *Radiographic Image Interpretation, Computer-Assisted ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To retrospectively evaluate the sensitivity of the performance of a computer-aided detection (CAD) system applied to full-field digital mammograms for detection of breast cancers in a screening group, with histologic findings as the reference standard.

MATERIALS AND METHODS: This study had institutional review board approval, and patient informed consent was waived. A commercially available CAD system was applied to the digital mammograms of 103 women (mean age, 51 years; range, 35-69 years) with 103 breast cancers detected with screening. Sensitivity values of the CAD system according to mammographic appearance, breast composition, and histologic findings were analyzed. Normal mammograms from 100 women (mean age, 54 years; age range, 35-75 years) with no mammographic and clinical abnormality during 2-year follow-up were used to determine false-positive CAD system marks. Differences between the cancer detection rates in fatty and dense breasts for the CAD system were compared by using the chi(2) test.

RESULTS: The CAD system correctly marked 99 (96.1%) of 103 breast cancers. The CAD system marked all 44 breast cancers that manifested as microcalcifications only, all 23 breast cancers that manifested as a mass with microcalcifications, and 32 (89%) of 36 lesions that appeared as a mass only. The sensitivity of the CAD system in the fatty breast group was 95% (59 of 62) and in the dense breast group was 98% (40 of 41) (P = .537). The CAD system correctly marked all 31 lesions of ductal carcinoma in situ (DCIS), all 22 lesions of invasive ductal carcinoma with DCIS, the single invasive lobular carcinoma lesion, and 45 (92%) of 49 lesions of invasive ductal carcinoma. On normal mammograms, the mean number of false-positive marks per patient was 1.80 (range, 0-10 marks; median, 1 mark).

CONCLUSION: The CAD system can correctly mark most (96.1%) asymptomatic breast cancers detected with digital mammographic screening, with acceptable false-positive marks (1.80 per patient).}, } @article {pmid17506030, year = {2007}, author = {Alemán, M and de la Barrera, S and Schierloh, P and Yokobori, N and Baldini, M and Musella, R and Abbate, E and Sasiain, M}, title = {Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response.}, journal = {European journal of immunology}, volume = {37}, number = {6}, pages = {1524-1537}, doi = {10.1002/eji.200636771}, pmid = {17506030}, issn = {0014-2980}, mesh = {Adult ; Antibodies, Monoclonal/immunology/pharmacology ; Antigens, CD/metabolism ; Apoptosis/*immunology ; B7-2 Antigen/metabolism ; CD36 Antigens/immunology ; Cell Adhesion Molecules/metabolism ; Cell Differentiation/immunology ; Coculture Techniques ; Cytochalasin D/pharmacology ; Dendritic Cells/drug effects/*immunology/metabolism ; Enzyme Inhibitors/pharmacology ; HLA-DR Antigens/metabolism ; Humans ; Imidazoles/pharmacology ; Immunoglobulins/metabolism ; Integrins/immunology ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; Kinetics ; Lectins, C-Type/metabolism ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/metabolism ; Middle Aged ; Mycobacterium tuberculosis/*immunology ; Neutrophils/*immunology ; Pyridines/pharmacology ; Receptors, Cell Surface/metabolism ; Receptors, Vitronectin/immunology ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils PMNapo (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-gamma release by DC and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DC, and it involves a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction, they affect the intracellular signals leading to DC maturation without requiring their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to lymphoproliferation, which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting inflammation and Mtb-induced PMNapo generating a specific immune activity.}, } @article {pmid17493477, year = {2007}, author = {Domanski, M and Coady, S and Fleg, J and Tian, X and Sachdev, V}, title = {Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]).}, journal = {The American journal of cardiology}, volume = {99}, number = {10}, pages = {1448-1450}, doi = {10.1016/j.amjcard.2006.12.080}, pmid = {17493477}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Cardiomyopathy, Dilated/complications/*drug therapy/*mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/etiology/mortality/physiopathology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Research Design ; Risk Factors ; Stroke Volume ; Survival Analysis ; Treatment Outcome ; }, abstract = {To determine whether statin therapy improves survival in patients with heart failure (HF) secondary to nonischemic dilated cardiomyopathy (non-IDC), data from 1,024 patients with non-IDC (New York Heart Association functional class III and IV HF) and left ventricular ejection fraction < or =0.35 who were enrolled in the BEST were analyzed. The association of statin therapy at the initial screening visit with all-cause and cardiovascular mortality was evaluated using multivariate Cox proportional hazards models. After adjusting for age, gender, race, systolic blood pressure, total cholesterol, New York Heart Association functional class IV, estimated glomerular filtration rate, current cigarette smoking, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor use, antiplatelet therapy, diabetes mellitus, treatment group (beta blocker or placebo), and hypertension, statin use was independently associated with decreased all-cause mortality (hazard ratio 0.38, confidence interval 0.18 to 0.82, p = 0.0134) and also with decreased cardiovascular death (hazard ratio 0.42, confidence interval 0.18 to 0.95, p = 0.037). In conclusion, in patients with moderate or severe HF due to non-IDC entered into BEST, statin therapy at entry was independently associated with a decrease in all-cause and cardiovascular mortality.}, } @article {pmid17485913, year = {2007}, author = {Nakamura, R and Nagashima, T and Sakakibara, M and Nakano, S and Tanabe, N and Fujimoto, H and Arai, M and Kadowaki, M and Oide, T and Tanizawa, T and Miyazaki, M}, title = {Angiosarcoma arising in the breast following breast-conserving surgery with radiation for breast carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {14}, number = {2}, pages = {245-249}, doi = {10.2325/jbcs.914}, pmid = {17485913}, issn = {1340-6868}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/therapy ; Chemotherapy, Adjuvant ; Female ; Hemangiosarcoma/*pathology/therapy ; Humans ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasms, Second Primary/*pathology/therapy ; Radiotherapy, Adjuvant ; Selective Estrogen Receptor Modulators/therapeutic use ; Tamoxifen/therapeutic use ; }, abstract = {We report a case of angiosarcoma arising in the breast following breast-conserving surgery with radiation therapy for breast carcinoma. The patient, a 49-year-old postmenopausal woman, had undergone breast-conserving surgery for invasive ductal carcinoma of the left breast (pT2 pN0 M0 Stage IIA). Adjuvant radiotherapy (50 Gy with a booster dose to the tumor bed of 10 Gy) was then performed for the residual breast tissue and the patient was treated with hormone therapy (tamoxifen, 20 mg daily) for 5 years. She presented with skin erosion with bleeding 10 years after the initial operation. Incisional biopsy revealed angiosarcoma of the breast, and total mastectomy was subsequently performed. The patient was the treated with chemotherapy (weekly paclitaxel, 80 mg/m2 x cycles) and has remained well without evidence of local or distant recurrence.}, } @article {pmid17479284, year = {2007}, author = {Lee, JS}, title = {GSTP1 promoter hypermethylation is an early event in breast carcinogenesis.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {450}, number = {6}, pages = {637-642}, pmid = {17479284}, issn = {0945-6317}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; *DNA Methylation ; Female ; Glutathione S-Transferase pi/*genetics/metabolism ; Humans ; Immunohistochemistry/methods ; Neoplasm Invasiveness ; Precancerous Conditions/*genetics/metabolism/pathology ; *Promoter Regions, Genetic ; Staining and Labeling ; Time Factors ; Tissue Distribution ; }, abstract = {Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. Pi-class glutathione-S-transferases (GSTP1) is inactivated by promoter hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific polymerase chain reaction, and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH), and normal breast tissue. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (p < 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.01 for UDH, p < 0.001 for DCIS and IDC). Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention.}, } @article {pmid17478157, year = {2007}, author = {Pascual-Figal, DA and Peñafiel, P and de la Morena, G and Redondo, B and Nicolás, F and Casas, T and Valdés, M}, title = {Relation of B-type natriuretic peptide levels before and after exercise and functional capacity in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {99}, number = {9}, pages = {1279-1283}, doi = {10.1016/j.amjcard.2006.12.050}, pmid = {17478157}, issn = {0002-9149}, mesh = {Adult ; Cardiomyopathy, Dilated/*blood/*physiopathology ; Exercise/*physiology ; Exercise Test ; Exercise Tolerance/*physiology ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Oxygen Consumption/physiology ; Pulmonary Gas Exchange/physiology ; Rest/*physiology ; }, abstract = {Although much is known about the value of B-type natriuretic peptide (BNP) at rest, the significance of the responsiveness of BNP during exercise in patients with chronic heart failure (HF) without coronary artery disease remains to be established. A role of BNP release during exercise in the functional disability of patients with chronic HF and idiopathic dilated cardiomyopathy (IDC) was hypothesized. One hundred five consecutive patients with an established diagnosis of HF and IDC who underwent symptom-limited cardiopulmonary exercise testing were studied. BNP was measured immediately before exercise and within 1 minute of the end of exercise. BNP at rest increased significantly at peak exercise (median from 66.5 (first, third quartiles 18, 168) to 72.0 pg/ml (26, 208), p <0.001), but BNP response was not uniform. BNP response increased in 63% of patients, did not change in 22%, and decreased in 15%. BNP at rest and BNP response showed an inverse correlation (p <0.001, r = -0.523). Aging and low left ventricular ejection fraction were independent predictors of higher BNP levels at rest, but lower BNP response. Beta-blocker therapy did not influence BNP response. BNP at rest correlated negatively with functional capacity (p <0.001, r = -0.516), whereas BNP response correlated positively (p = 0.002, r = 0.326). Patients with BNP release (vs patients without) had higher maximum oxygen consumption (19.2 +/- 5.1 vs 15.9 +/- 3.6, p <0.001), better functional capacity (59 +/- 13% vs 50 +/- 15%, p = 0.002), and lower minute ventilation/carbon dioxide production slope (33.6 +/- 4.8 vs 36.5 +/- 7.7, p = 0.026) independent of other clinical parameters. In conclusion, BNP release during exercise could be a determinant of functional capacity in patients with chronic HF and IDC.}, } @article {pmid17472276, year = {2003}, author = {Gavrilov, I and Nacheva, M and Tzingilev, D}, title = {Familial breast cancer. Part IV: survival of familial breast cancer in Bulgarian patients.}, journal = {Journal of B.U.ON. : official journal of the Balkan Union of Oncology}, volume = {8}, number = {4}, pages = {351-356}, pmid = {17472276}, issn = {1107-0625}, abstract = {PURPOSE: The aim of part IV of this study was to register and compare the survival rates of sporadic and familial breast cancer, and to estimate the prognostic value of familial predisposition of the disease as a risk factor.

PATIENTS AND METHODS: We investigated retrospectively 504 patients belonging to families with accumulation of the disease (study group, group I) and 300 patients with the sporadic form of breast cancer (control group, group II). All patients were diagnosed, treated, and followed-up at the Clinic of Thoracic Surgery, National Oncological Centre. For determination of the familial predisposition we used the Anderson's classification. The statistical significance of the difference between two groups and subgroups was evaluated by the x(2) Pearson's test and Student's paired t-test.

RESULTS: Women with familial breast cancer were characterized by worse survival rates compared to the sporadic cases. Of the patients in group I 20.79% survived more than 5 years versus 76.74% in group II (p <0.0000). Group I patients with first degree of kinship had the lowest survival rates. Highly significant differences were found in survival, depending on stage: in group I stage IIA patients the survival was 42.86% versus 97.73% for group II; in IIB it was 14.17% versus 89.41%; and in IIIA it was 4.76% versus 75.00%, respectively. Tumor size, lymph nodes status, metastases and steroid receptors also showed a high statistical difference in survival between the 2 groups. Five-year survival in group I patients without metastases was 22.34%, while it was 80.71% in group II. In patients with metastases 4-year survival rates were 2.94% and 22.22%, respectively. Estrogen receptor (ER)-negative patients in groups I and II had 5-year survival of 17.41% and 72.06%, respectively. Progesterone receptor (PR)-negative patients in groups I and II had 5-year survival of 17.50% and 83.67%, respectively. Invasive lobular and invasive ductal carcinoma showed very poor survival in both groups (18.75% and 17.73% in group I versus 53.33% and 77.48% in group II, respectively).

CONCLUSION: Familial breast cancer displays particular clinical characteristics that differ from the sporadic form of the disease in terms of clinical, histological and biochemical features. Our results show that patients with familial breast cancer have significantly lower survival rates in comparison with women with the sporadic form of the disease. The need for surveillance and diagnosis of the disease at an earlier stage is crucial for women with familial predisposition for breast cancer.}, } @article {pmid17466527, year = {2007}, author = {O'Rourke, JA and Graham, MA and Vodkin, L and Gonzalez, DO and Cianzio, SR and Shoemaker, RC}, title = {Recovering from iron deficiency chlorosis in near-isogenic soybeans: a microarray study.}, journal = {Plant physiology and biochemistry : PPB}, volume = {45}, number = {5}, pages = {287-292}, doi = {10.1016/j.plaphy.2007.03.008}, pmid = {17466527}, issn = {0981-9428}, mesh = {Adaptation, Physiological/genetics ; DNA, Plant/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Iron Deficiencies ; *Oligonucleotide Array Sequence Analysis ; Plant Diseases/*genetics ; Plant Proteins/metabolism ; Soil/analysis ; Soybeans/*genetics/*metabolism ; }, abstract = {Iron deficiency chlorosis (IDC) in soybeans has proven to be a perennial problem in the calcareous soils of the U.S. upper Midwest. A historically difficult trait to study in fields, the use of hydroponics in a controlled greenhouse environment has provided a mechanism to study genetic variation while limiting environmental complications. IDC susceptible plants growing in calcareous soils and in iron-controlled hydroponic experiments often exhibit a characteristic chlorotic phenotype early in the growing season but are able to re-green later in the season. To examine the changes in gene expression of these plants, near-isogenic lines, iron efficient PI548553 (Clark) and iron inefficient PI547430 (IsoClark), developed for their response to iron deficiency stress [USDA, ARS, National Genetic Resources Program, Germplasm Resources Information Network - GRIN. (Online Database) National Germplasm Resources Laboratory, Beltsville, MD, 2004. Available: http://www.ars.grin.gov/cgi-bin/npgs/html/acc_search.pl?accid=PI+547430. [22] were grown in iron-deficient hydroponic conditions for one week, then transferred to iron sufficient conditions for another week. This induced a phenotypic response mimicking the growth of the plants in the field; initial chlorosis followed by re-greening. RNA was isolated from root tissue and transcript profiles were examined between the two near-isogenic lines using publicly available cDNA microarrays. By alleviating the iron deficiency stress our expectation was that plants would return to baseline expression levels. However, the microarray comparison identified four cDNAs that were under-expressed by a two-fold or greater difference in the iron inefficient plant compared to the iron efficient plant. This differential expression was re-examined and confirmed by real time PCR experimentation. Control experiments showed that these genes are not differentially expressed in plants grown continually under iron rich hydroponic conditions. The expression differences suggest potential residual effects of iron deficiency on plant health.}, } @article {pmid17462982, year = {2007}, author = {Perez-Fidalgo, JA and Chirivella, I and Laforga, J and Colio, JM and Blanes, MD and Baydal, R and Roselló, S and De-la-Morena, E and Lluch, A}, title = {Parotid gland metastasis of a breast cancer.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {9}, number = {4}, pages = {264-265}, doi = {10.1007/s12094-007-0051-2}, pmid = {17462982}, issn = {1699-048X}, mesh = {Anastrozole ; Antibiotics, Antineoplastic/administration & dosage/therapeutic use ; Antimetabolites, Antineoplastic/administration & dosage/therapeutic use ; Antineoplastic Agents, Alkylating/administration & dosage/therapeutic use ; Antineoplastic Agents, Hormonal/administration & dosage/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use ; *Breast Neoplasms/diagnosis/drug therapy/surgery ; Capecitabine ; *Carcinoma, Ductal, Breast/drug therapy/pathology/radiotherapy/secondary/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage/therapeutic use ; Deoxycytidine/administration & dosage/analogs & derivatives/therapeutic use ; Doxorubicin/administration & dosage/therapeutic use ; Female ; Fluorouracil/administration & dosage/analogs & derivatives/therapeutic use ; Humans ; Immunohistochemistry ; Mastectomy, Radical ; Middle Aged ; Nitriles/administration & dosage/therapeutic use ; Parotid Gland/pathology/surgery ; Parotid Neoplasms/diagnosis/drug therapy/pathology/radiotherapy/*secondary/surgery ; Receptors, Estrogen/analysis ; Time Factors ; Treatment Outcome ; Triazoles/administration & dosage/therapeutic use ; }, abstract = {Parotid gland metastases from malignant tumors are extremely rare. A 61-year-old woman was diagnosed with an early breast cancer with no expression of oestrogen and progesterone receptors. Five years later the patient presented a tumour in parotid gland. After total parotidectomy, microscopic analysis of the gland demonstrated an invasive duct carcinoma (IDC) with positive expression of oestrogen receptor. The patient was treated with chemotherapy followed by complementary local radiotherapy. Diagnosis of a metastasic tumour in parotid gland poses a challenge. In our case an immunohistochemical study of oestrogen receptor was fundamental to establish a diagnosis.}, } @article {pmid17460770, year = {2007}, author = {Rashid-Kolvear, F and Pintilie, M and Done, SJ}, title = {Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {9}, number = {4}, pages = {265-270}, pmid = {17460770}, issn = {1476-5586}, mesh = {Breast Neoplasms/etiology/*genetics/pathology ; Carcinoma, Ductal, Breast/etiology/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/etiology/*genetics/pathology ; Chromosomal Instability/genetics ; Chromosomes, Human, Pair 17/*genetics ; Female ; Humans ; Telomere/*genetics ; }, abstract = {It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared normal breast epithelium, duct carcinoma in situ (DCIS), and invasive duct carcinoma (IDC) from 18 patients. Telomere length was specifically measured on chromosome 17q and was found to be shorter in DCIS and IDC than in normal breast epithelial cells, with more heterogeneity in telomere length in DCIS associated with IDC than in DCIS alone. More importantly, we found that the shortening of telomere on chromosome 17q is greater than the average shortening of all telomeres. This finding indicates that telomere shortening is not simply the result of the end replication problem; otherwise, all telomeres should be subjected to the same rate of telomere shortening. It seems there are mechanisms that preferentially erode some telomeres more than others or preferentially protect some chromosome ends. Our results suggest that the increased level of telomere shortening on 17q may be involved in chromosome instability and the progression of DCIS.}, } @article {pmid17458558, year = {2007}, author = {Tawfik, O and Kimler, BF and Davis, M and Stasik, C and Lai, SM and Mayo, MS and Fan, F and Donahue, JK and Damjanov, I and Thomas, P and Connor, C and Jewell, WR and Smith, H and Fabian, CJ}, title = {Grading invasive ductal carcinoma of the breast: advantages of using automated proliferation index instead of mitotic count.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {450}, number = {6}, pages = {627-636}, pmid = {17458558}, issn = {0945-6317}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Proliferation ; Cohort Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Middle Aged ; Mitotic Index ; Neoplasm Invasiveness ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; }, abstract = {Breast carcinomas are graded according to the "Nottingham modification of the Bloom-Richardson system" (SBR). The system is hindered, however, by lack of precision in assessing all three parameters including nuclear grade, mitosis, and tubular formation, leading to an element of subjectivity. Our objective was to evaluate a new grading system [the nuclear grade plus proliferation (N+P) system] for subjectivity, ease, and better representation of tumor biology. Its components are nuclear grade and automated proliferation index. Invasive ductal carcinomas, consisting of 137 SBR grade I, 247 grade II, and 266 grade III, were re-evaluated by the N+P system. The two systems were compared with each other and correlated with patients' overall survival, tumor size, angiolymphatic invasion, lymph node status, and biomarker status including estrogen receptor, progesterone receptor, p53, epidermal growth factor receptor, BCL-2, and Her-2. Although there was an agreement between the two systems with histologic and prognostic parameters studied, there was 37% disagreement when grading individual tumors. Fifty-three percent of SBR grade II tumors were "down-graded" to N+P grade I, and 7% were "up-graded" to N+P grade III. Distinction among the different histologic grades for overall survival curves was better indicated by the N+P than the SBR system.}, } @article {pmid17448240, year = {2007}, author = {von Euw, EM and Barrio, MM and Furman, D and Bianchini, M and Levy, EM and Yee, C and Li, Y and Wainstok, R and Mordoh, J}, title = {Monocyte-derived dendritic cells loaded with a mixture of apoptotic/necrotic melanoma cells efficiently cross-present gp100 and MART-1 antigens to specific CD8(+) T lymphocytes.}, journal = {Journal of translational medicine}, volume = {5}, number = {}, pages = {19}, pmid = {17448240}, issn = {1479-5876}, mesh = {Antigens, Neoplasm/*immunology ; *Apoptosis/drug effects/radiation effects ; CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology/radiation effects ; Cell Differentiation/drug effects/radiation effects ; Cell Line, Tumor ; Cell Movement/drug effects/radiation effects ; Chemokine CCL19/pharmacology ; Coculture Techniques ; Cross-Priming/drug effects/*immunology/radiation effects ; Dendritic Cells/cytology/drug effects/*immunology/ultrastructure ; Epitopes/immunology ; Gamma Rays ; Humans ; Interleukin-10/immunology ; Interleukin-12/immunology ; MART-1 Antigen ; Melanoma/immunology/*pathology/ultrastructure ; Membrane Glycoproteins/*immunology ; Monocytes/cytology/immunology ; Necrosis ; Neoplasm Proteins/*immunology ; Phagocytosis/drug effects/immunology/radiation effects ; Receptors, CCR7/immunology ; Time Factors ; gp100 Melanoma Antigen ; }, abstract = {BACKGROUND: In the present study, we demonstrate, in rigorous fashion, that human monocyte-derived immature dendritic cells (DCs) can efficiently cross-present tumor-associated antigens when co-cultured with a mixture of human melanoma cells rendered apoptotic/necrotic by gamma irradiation (Apo-Nec cells).

METHODS: We evaluated the phagocytosis of Apo-Nec cells by FACS after PKH26 and PKH67 staining of DCs and Apo-Nec cells at different times of coculture. The kinetics of the process was also followed by electron microscopy. DCs maturation was also studied monitoring the expression of specific markers, migration towards specific chemokines and the ability to cross-present in vitro the native melanoma-associated Ags MelanA/MART-1 and gp100.

RESULTS: Apo-Nec cells were efficiently phagocytosed by immature DCs (iDC) (55 +/- 10.5%) at 12 hs of coculture. By 12-24 hs we observed digested Apo-Nec cells inside DCs and large empty vacuoles as part of the cellular processing. Loading with Apo-Nec cells induced DCs maturation to levels achieved using LPS treatment, as measured by: i) the decrease in FITC-Dextran uptake (iDC: 81 +/- 5%; DC/Apo-Nec 33 +/- 12%); ii) the cell surface up-regulation of CD80, CD86, CD83, CCR7, CD40, HLA-I and HLA-II and iii) an increased in vitro migration towards MIP-3beta. DC/Apo-Nec isolated from HLA-A*0201 donors were able to induce >600 pg/ml IFN-gamma secretion of CTL clones specific for MelanA/MART-1 and gp100 Ags after 6 hs and up to 48 hs of coculture, demonstrating efficient cross-presentation of the native Ags. Intracellular IL-12 was detected in DC/Apo-Nec 24 hs post-coculture while IL-10 did not change.

CONCLUSION: We conclude that the use of a mixture of four apoptotic/necrotic melanoma cell lines is a suitable source of native melanoma Ags that provides maturation signals for DCs, increases migration to MIP-3beta and allows Ag cross-presentation. This strategy could be exploited for vaccination of melanoma patients.}, } @article {pmid17437747, year = {2007}, author = {Rigo, F and Gherardi, S and Galderisi, M and Sicari, R and Picano, E}, title = {The independent prognostic value of contractile and coronary flow reserve determined by dipyridamole stress echocardiography in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {99}, number = {8}, pages = {1154-1158}, doi = {10.1016/j.amjcard.2006.11.049}, pmid = {17437747}, issn = {0002-9149}, mesh = {Blood Flow Velocity/drug effects/physiology ; Bundle-Branch Block/physiopathology ; Cardiac Output, Low/physiopathology ; Cardiomyopathy, Dilated/diagnostic imaging/*physiopathology ; Coronary Angiography ; Coronary Circulation/drug effects/*physiology ; *Dipyridamole ; Echocardiography, Doppler, Pulsed ; *Echocardiography, Stress ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency/physiopathology ; Myocardial Contraction/drug effects/*physiology ; Prognosis ; Prospective Studies ; Stroke Volume/drug effects/physiology ; Survival Rate ; *Vasodilator Agents ; Ventricular Function/drug effects/physiology ; }, abstract = {The aim of this study was to evaluate the prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in assessing inotropic response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography. All patients had ejection fractions <40% (mean 33 +/- 7%) and angiographically normal coronary arteries, with New York Heart Association class 0.25. All patients were followed for a median of 24 months. Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was 2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p <0.000). Forty-two patients (32%) had inotropic reserve. During follow-up, 19 patients died, and 34 showed worsening of New York Heart Association class. The worst outcomes were observed in those patients with abnormal CFR and no inotropic reserve with high-dose dipyridamole. In a Cox model, mitral insufficiency (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.8), New York Heart Association class (HR 2.0, 95% CI 1.1 to 3.7), abnormal CFR (HR 2.8, 95% CI 1.0 to 8.5), wall motion score index at rest (HR 3.5, 95% CI 1.3 to 9.8), and the absence of inotropic reserve with high-dose dipyridamole (HR 2.3, 95% CI 1.06 to 5.1) were independent predictors of survival. In conclusion, in patients with IDC, CFR is often impaired. Reduced CFR and the absence of an inotropic response during vasodilator stress are additive in predicting a worse prognosis.}, } @article {pmid17416753, year = {2007}, author = {Ohuchida, K and Mizumoto, K and Yu, J and Yamaguchi, H and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {S100A6 is increased in a stepwise manner during pancreatic carcinogenesis: clinical value of expression analysis in 98 pancreatic juice samples.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {16}, number = {4}, pages = {649-654}, doi = {10.1158/1055-9965.EPI-06-0157}, pmid = {17416753}, issn = {1055-9965}, mesh = {Aged ; Biomarkers, Tumor/metabolism ; Cell Cycle Proteins/*metabolism ; Chi-Square Distribution ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Juice/*chemistry ; Pancreatic Neoplasms/*metabolism/pathology ; RNA, Neoplasm/analysis ; ROC Curve ; Reverse Transcriptase Polymerase Chain Reaction ; S100 Calcium Binding Protein A6 ; S100 Proteins/*metabolism ; Statistics, Nonparametric ; }, abstract = {There are few reports describing the diagnostic significance of S100A6 expression in clinical samples obtained from patients with pancreatic disease. In the present study, we measured S100A6 expression in pancreatic tissues and juice to evaluate its involvement in pancreatic carcinogenesis. We did quantitative real-time reverse transcription-PCR to measure mRNA expression in microdissected cells and pancreatic juice samples. Microdissected invasive ductal carcinoma and intraductal papillary mucinous neoplasm (IPMN) cells expressed significantly higher levels of S100A6 than did microdissected pancreatitis-affected epithelial and normal cells (all comparison; P < 0.008). Median levels of S100A6 in invasive ductal carcinoma were higher than those in IPMN, and those in pancreatitis-affected epithelial cells tended to be higher than those in normal cells, although these differences were not statistically significant. In analyses of pancreatic juice, IPMN and pancreatic cancer samples expressed significantly higher levels of S100A6 than did chronic pancreatitis samples (both; P < 0.017), but levels in pancreatic cancer and IPMN samples did not differ form each other. Receiver operating characteristic (ROC) curve analysis revealed that measurement of S100A6 was useful for discriminating cancer (area under the ROC curve, 0.864) or IPMN (area under the ROC curve, 0.749) from chronic pancreatitis. The present data suggest that expression of S100A6 is increased in a stepwise manner during pancreatic carcinogenesis and may be a biomarker for evaluating malignant potential. Measurement of S100A6 in pancreatic juice may be useful to detect early pancreatic cancer or identify individuals with high-risk lesions that may progress to pancreatic cancer.}, } @article {pmid17415922, year = {2007}, author = {Kuroda, N and Fujishima, N and Ohara, M and Hirouchi, T and Mizuno, K and Lee, GH}, title = {Invasive ductal carcinoma of the breast with signet-ring cell and mucinous carcinoma components: diagnostic utility of immunocytochemistry of signet-ring cells in aspiration cytology materials.}, journal = {Diagnostic cytopathology}, volume = {35}, number = {3}, pages = {171-173}, doi = {10.1002/dc.20609}, pmid = {17415922}, issn = {8755-1039}, mesh = {Adenocarcinoma, Mucinous/*diagnosis ; Aged ; Biopsy, Needle ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Carcinoma, Signet Ring Cell/*diagnosis ; Female ; Humans ; Immunohistochemistry ; }, abstract = {Breast cancer with signet-ring cells is very rare. In this article, we present a case of invasive ductal carcinoma with signet-ring cells and mucinous carcinoma components, which could be diagnosed as a primary cancer by immunocytochemical study of fine-needle aspiration cytology material. A 73-yr-old Japanese woman noticed a palpable mass in the left breast. The aspiration cytology disclosed the monotonous proliferation of signet-ring cell with cytological atypia. The immunocytochemical examination of neoplastic cells showed a positive reaction for estrogen receptor. The extensive examination of body before the operation did not disclose any tumors in other anatomic sites. The histological examination of surgically resected breast tumor showed invasive ductal carcinoma with foci of signet-ring cell and mucinous carcinomas. Finally, our preliminary report suggests that immunocytochemical examination of aspiration cytology materials may provide useful information in searching the primary site of breast carcinoma with signet-ring cells.}, } @article {pmid17405379, year = {2007}, author = {Lim, YG and Kim, KK and Park, KS}, title = {ECG recording on a bed during sleep without direct skin-contact.}, journal = {IEEE transactions on bio-medical engineering}, volume = {54}, number = {4}, pages = {718-725}, doi = {10.1109/TBME.2006.889194}, pmid = {17405379}, issn = {0018-9294}, mesh = {*Beds ; Diagnosis, Computer-Assisted/*instrumentation/methods ; Electrocardiography, Ambulatory/*instrumentation/methods ; *Electrodes ; Electronics, Medical ; Equipment Design ; Equipment Failure Analysis ; Heart/*physiology ; Humans ; Polysomnography/*instrumentation/methods ; Skin Physiological Phenomena ; Sleep/*physiology ; }, abstract = {A new indirect contact (IDC) electrocardiogram (ECG) measurement method (IDC-ECG) for monitoring ECG during sleep that is adequate for long-term use is provided. The provided method did not require any direct conductive contact between the instrument and bare skin. This method utilizes an array of high-input-impedance active electrodes fixed on the mattress and an indirect-skin-contact ground made of a large conductive textile sheet. A thin cotton bedcover covered the mattress, electrodes, and conductive textile, and the participants were positioned on the mattress over the bedcover. An ECG was successfully obtained, although the signal quality was lower and the motion artifact was larger than in conventional direct-contact measurements (DC-ECG). The results showed that further studies are required to apply the provided method to an ECG diagnosis of cardiovascular diseases. However, currently the method can be used for HRV assessment with easy discrimination of R-peaks.}, } @article {pmid17403919, year = {2007}, author = {Fiore, F and Castella, B and Nuschak, B and Bertieri, R and Mariani, S and Bruno, B and Pantaleoni, F and Foglietta, M and Boccadoro, M and Massaia, M}, title = {Enhanced ability of dendritic cells to stimulate innate and adaptive immunity on short-term incubation with zoledronic acid.}, journal = {Blood}, volume = {110}, number = {3}, pages = {921-927}, doi = {10.1182/blood-2006-09-044321}, pmid = {17403919}, issn = {0006-4971}, mesh = {Adjuvants, Immunologic/*pharmacology ; Bone Density Conservation Agents/pharmacology ; Cancer Vaccines/immunology ; Cell Proliferation/drug effects ; Cells, Cultured ; Dendritic Cells/*immunology ; Diphosphonates/*pharmacology ; Histocompatibility Antigens/immunology ; Humans ; Imidazoles/*pharmacology ; Immunity, Innate/*drug effects ; Immunologic Memory/drug effects ; Immunotherapy, Adoptive ; Lymphocyte Activation/drug effects ; Monocytes/*immunology ; Neoplasms/immunology/therapy ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; T-Lymphocytes/immunology ; Time Factors ; Zoledronic Acid ; }, abstract = {Vgamma9/Vdelta2 (gammadelta) T cells play a major role in innate immunity against microbes, stressed, and tumor cells. They represent less than 5% of peripheral blood lymphocytes but can be activated and expanded in vitro by aminobisphosphonates (ABP)-treated monocytes. The aim of this work was to determine whether ABP-treated dendritic cells (DCs) can also activate gammadelta T cells and regulate immune responses mediated by conventional alphabeta T cells. Highly purified immature (iDC) and mature DC (mDC) were generated from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol-treated iDC and mDC retained their immunostimulatory properties and induced the vigorous expansion of central memory and effector memory gammadelta T cells. gammadelta T cells displayed antitumor activity and appropriate cell surface antigens to target secondary lymphoid organs and exert costimulatory activity. Antigen-specific MHC-restricted immune responses, mediated by conventional alphabeta T cells, were improved by the concurrent gammadelta T-cell activation. In conclusion, large numbers of gammadelta T cells with effector and costimulatory activities are rapidly generated by Zol-treated iDC/mDC. This strategy is worthy of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.}, } @article {pmid17390170, year = {2007}, author = {Miura, F and Takada, T and Amano, H and Yoshida, M and Isaka, T and Toyota, N and Wada, K and Takagi, K and Kato, K}, title = {Repeated pancreatectomy after pancreatoduodenectomy.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {11}, number = {2}, pages = {179-186}, pmid = {17390170}, issn = {1091-255X}, mesh = {Adult ; Aged ; Anastomosis, Surgical ; Carcinoma, Pancreatic Ductal/surgery ; Constriction, Pathologic ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/surgery ; *Pancreatectomy ; Pancreatic Neoplasms/*surgery ; *Pancreaticoduodenectomy/adverse effects ; Reoperation ; }, abstract = {BACKGROUND: When pancreatic duct dilatation is found in the patient having undergone pancreatoduodenectomy (PD), observation is chosen in most cases. Similarly, recurrent tumor in the remnant pancreas of invasive ductal carcinoma (IDC) of the pancreas is seldom indicated for resection. We have aggressively performed repeated pancreatectomy for these cases and obtained good results.

METHODS: Repeated pancreatectomy after PD was performed for three types of circumstances: (1) pancreatodigestive anastomotic stricture; (2) neoplasm after intraductal papillary mucinous neoplasm (IPMN); and (3) recurrence of IDC of the pancreas.

RESULTS: Resection of anastomosis and reanastomosis was performed for pancreatodigestive stricture in four patients. Symptoms derived from pancreatitis in three patients resolved by the second operation and did not recur during follow-up. None of the four patients required pancreatic enzyme substitution because of clinically overt malabsorption, and the defecation frequency of the four patients was within twice a day. Mild diabetes mellitus has been identified in only one patient who had diabetes mellitus before the second surgery. Completion pancreatectomy and pancreatic tail resection was performed for recurrence in two patients and IDC in one patient, respectively, after PD for IPMN. Intrapancreatic recurrences of IPMN in two patients existed in the main pancreatic ducts. As CT revealed pancreatic duct dilatation but not intraductal tumors, recurrences were not correctly diagnosed before the second operation. Completion pancreatectomy was performed for recurrence of IDC in two patients. One patient who underwent completion pancreatectomy for recurrence of IDC survived 66/44 months after the first/second operation.

CONCLUSION: Repeated pancreatectomy should be performed for patients with pancreatodigestive anastomotic stricture to preserve remnant pancreatic function and for patients with neoplasm or pancreatic duct dilatation after PD for IPMN, and repeated pancreatectomy for recurrence of IDC might be indicated for selected patients.}, } @article {pmid17389037, year = {2007}, author = {Turashvili, G and Bouchal, J and Baumforth, K and Wei, W and Dziechciarkova, M and Ehrmann, J and Klein, J and Fridman, E and Skarda, J and Srovnal, J and Hajduch, M and Murray, P and Kolar, Z}, title = {Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.}, journal = {BMC cancer}, volume = {7}, number = {}, pages = {55}, pmid = {17389037}, issn = {1471-2407}, support = {F31 NR007844/NR/NINR NIH HHS/United States ; R01 NR008425/NR/NINR NIH HHS/United States ; }, mesh = {Biomarkers ; Breast/metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Collagen Type III/genetics ; Extracellular Matrix Proteins/genetics ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lasers ; Microdissection/*methods ; Tissue Array Analysis/*methods ; }, abstract = {BACKGROUND: Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells.

METHODS: We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR.

RESULTS: Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC.

CONCLUSION: IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.}, } @article {pmid17385712, year = {2007}, author = {Ogura, S and Ohdaira, T and Hozumi, Y and Omoto, Y and Nagai, H}, title = {Metastasis-related factors expressed in pT1 pN0 breast cancer: assessment of recurrence risk.}, journal = {Journal of surgical oncology}, volume = {96}, number = {1}, pages = {46-53}, doi = {10.1002/jso.20805}, pmid = {17385712}, issn = {0022-4790}, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*metabolism ; Logistic Models ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinases/*metabolism ; Middle Aged ; *Neoplasm Recurrence, Local/etiology ; Postoperative Period ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Tissue Inhibitor of Metalloproteinase-2/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {OBJECTIVES: Previous reports have indicated that small breast cancers without lymph node metastasis present a favorable prognosis. However, 10-20% of patients with T1 N0 invasive ductal carcinoma experience recurrence and have a poor prognosis. The objective of this study was to examine whether certain metastasis-related factors are prognostic of cancer recurrence in such patients at risk for relapse.

METHODS: Nineteen patients with the carcinoma who had recurrence 1-15 years after margin-free resection were examined. The control group consisted of 20 patients with pT1 pN0 invasive ductal carcinoma who had no recurrence for > or =10 years after radical surgery. The two groups were compared with respect to clinical profiles, conventional neoplastic features, and immunohistochemical expressions of 16 metastasis-related factors.

RESULTS: No significant difference was found between the two groups in clinical profiles and conventional neoplastic features. However, six factors (MMP-2, MT1-MMP, T1MP-2, VEGF, cMET, and PCNA) were significantly expressed in the recurrence group against the control group. MMP-9 was significantly less expressed in the recurrence group. Of these factors, MMP-2, MT1-MMP, and VEGF showed the highest adjusted odds ratios.

CONCLUSION: MMP family and growth factors may be promising predictors of recurrence risk of early stage breast cancer.}, } @article {pmid17383681, year = {2007}, author = {Sharma, G and Mirza, S and Prasad, CP and Srivastava, A and Gupta, SD and Ralhan, R}, title = {Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients.}, journal = {Life sciences}, volume = {80}, number = {20}, pages = {1873-1881}, doi = {10.1016/j.lfs.2007.02.026}, pmid = {17383681}, issn = {0024-3205}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood/*genetics ; Breast Neoplasms/*blood/diagnosis ; Cyclin-Dependent Kinase 2/genetics/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism ; DNA Methylation ; DNA, Neoplasm/*metabolism ; Female ; Humans ; Immunohistochemistry/methods ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Middle Aged ; Nerve Tissue Proteins/genetics/metabolism ; Promoter Regions, Genetic/*physiology ; Serum/chemistry ; Tumor Suppressor Protein p14ARF/*genetics/metabolism ; }, abstract = {Epigenetic mechanisms such as DNA methylation play important role in cancer. Epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prediction of disease prognosis. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for biomarker analyses. The aim of this study is to determine the correlation between methylation status of multiple cancer genes, p16(INK4A), p14(ARF), Cyclin D2 and Slit2 in invasive ductal carcinoma of the breast and paired serum DNA and clinicopathological parameters. Of the 36 breast cancer patients investigated, 31 (86%) tumors and 30 (83%) paired sera showed methylation of at least one of these 4 genes. Methylation frequencies varied from 27% for CyclinD2, 44% for p16(INK4A), 47% for p14(ARF) to 58% for Slit2. There was concordance between DNA methylation in tumor and paired serum DNA of each gene. This study underscores the potential utility of DNA methylation based screening of serum as a surrogate marker for tumor DNA methylation status of these genes in breast cancer. Further, expression profile of p16(INK4A) could be linked to epigenetic events, thus suggesting this pathway as a potential target for therapeutic strategies based on reversal of epigenetic silencing.}, } @article {pmid17382138, year = {2007}, author = {Abarbanel, J and Marcus, EL}, title = {Impaired detrusor contractility in community-dwelling elderly presenting with lower urinary tract symptoms.}, journal = {Urology}, volume = {69}, number = {3}, pages = {436-440}, doi = {10.1016/j.urology.2006.11.019}, pmid = {17382138}, issn = {1527-9995}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Muscle Contraction/physiology ; Retrospective Studies ; Urinary Bladder/*physiopathology ; Urinary Bladder, Overactive/*physiopathology ; Urination Disorders/*physiopathology ; Urodynamics ; }, abstract = {OBJECTIVES: To determine the prevalence of impaired detrusor contractility (IDC) with and without detrusor hyperactivity (DH) among community-dwelling elderly with lower urinary tract symptoms and to identify which patients are at a greater risk of having a hypocontractile detrusor.

METHODS: We performed a retrospective chart review of all patients 70 years old or older with storage and/or voiding lower urinary tract symptoms who had undergone urodynamic pressure-flow studies in a urodynamic referral center during a 2-year period.

RESULTS: During the study period, 181 patients (82 men [45%] and 99 women [55%]), aged 70 years or older (mean age 75.7 +/- 4.8), underwent urodynamic studies. IDC was detected in 39 (48%) of the 82 men and in 12 (12%) of the 99 women. Two thirds of the men and one half of the women with IDC also had involuntary detrusor contractions during the filling phase and/or low bladder compliance. The prevalence of IDC/DH-IDC was significantly greater in those with a history of urinary retention and an indwelling urethral catheter.

CONCLUSIONS: Detrusor-impaired contractility is an important pathophysiologic mechanism in older patients with lower urinary tract symptoms, especially in men. Establishing the diagnosis by urodynamic pressure-flow studies is crucial for determining treatment--potentially harmful to this vulnerable population--from objective parameters rather than by empirical decisions.}, } @article {pmid17380381, year = {2008}, author = {Aulmann, S and Penzel, R and Longerich, T and Funke, B and Schirmacher, P and Sinn, HP}, title = {Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer.}, journal = {Breast cancer research and treatment}, volume = {107}, number = {3}, pages = {331-335}, doi = {10.1007/s10549-007-9557-0}, pmid = {17380381}, issn = {0167-6806}, mesh = {Adult ; Breast Neoplasms/genetics/*pathology ; Cadherins/analysis ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; DNA, Mitochondrial/genetics ; Female ; Humans ; Middle Aged ; Mutation ; Neoplasms, Second Primary/genetics/*pathology ; }, abstract = {Lobular carcinoma in situ (LCIS) of the breast is generally considered an indicator for a bilaterally increased risk of invasive breast cancer (IBC). However, as recent studies suggested a clonal relationship between a subset of synchronous LCIS and invasive lobular carcinomas (ILC), we aimed to examine a possible precursor role for LCIS and IBC occurring in the same breast at a later time. Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy. For each case, mitochondrial DNA heteroplasmy was analyzed in normal mammary gland epithelia, LCIS and IBC by PCR, direct DNA sequencing and phylogenetic tree clustering. Two cases of LCIS and ILC showed identical patterns of heteroplasmy. In one further case, additional mtDNA mutations were present in the ILC following LCIS. The remaining two cases of ILC and all 4 IDC were clonally unrelated to the previously diagnosed LCIS. While the overall risk for the development of invasive breast cancer following LCIS is relatively low and the majority of cases are clonally unrelated, our data clearly show that some LCIS eventually do progress to ILC. Thus, LCIS represents both an indicator lesion for an increased risk of subsequent invasive breast cancer and in some cases a precursor of ILC.}, } @article {pmid17365021, year = {2007}, author = {Jin, Y and Fuller, L and Esquenazi, V and Blomberg, BB and Burke, GW and Ciancio, G and Tzakis, AG and Ricordi, C and Miller, J}, title = {Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells.}, journal = {Immunological investigations}, volume = {36}, number = {2}, pages = {213-232}, doi = {10.1080/08820130601015775}, pmid = {17365021}, issn = {0882-0139}, support = {5 R01-DK25243-25/DK/NIDDK NIH HHS/United States ; }, mesh = {CD4-Positive T-Lymphocytes/immunology ; Cell Communication/immunology ; Dendritic Cells/*immunology ; Down-Regulation ; Epstein-Barr Virus Infections/immunology ; Forkhead Transcription Factors/biosynthesis/immunology ; Herpesvirus 4, Human/immunology ; Humans ; Immunity, Cellular ; Interleukin-2 Receptor alpha Subunit/biosynthesis/immunology ; Kidney Transplantation/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAb and TAp with similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL-4, IL-10, Foxp3, and differentially expressed TGFbeta. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were approximately two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAb and TAp were not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBL response to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact.}, } @article {pmid17363347, year = {2007}, author = {Reynolds, JL and Mahajan, SD and Sykes, DE and Schwartz, SA and Nair, MP}, title = {Proteomic analyses of methamphetamine (METH)-induced differential protein expression by immature dendritic cells (IDC).}, journal = {Biochimica et biophysica acta}, volume = {1774}, number = {4}, pages = {433-442}, pmid = {17363347}, issn = {0006-3002}, support = {R01 DA12366/DA/NIDA NIH HHS/United States ; R01 DA021537/DA/NIDA NIH HHS/United States ; R01 DA012366-09/DA/NIDA NIH HHS/United States ; R01 DA14218/DA/NIDA NIH HHS/United States ; R01 DA15628/DA/NIDA NIH HHS/United States ; R01 DA014218/DA/NIDA NIH HHS/United States ; R01 DA012366/DA/NIDA NIH HHS/United States ; R01 DA014218-06/DA/NIDA NIH HHS/United States ; F32 DA021535/DA/NIDA NIH HHS/United States ; R01 DA021537-02/DA/NIDA NIH HHS/United States ; 1 F32 DA02153501/DA/NIDA NIH HHS/United States ; F32 DA021535-01/DA/NIDA NIH HHS/United States ; R01 DA015628/DA/NIDA NIH HHS/United States ; }, mesh = {Dendritic Cells/drug effects/immunology/*metabolism/virology ; Gene Expression Regulation/drug effects ; HIV-1/physiology ; Humans ; Methamphetamine/*pharmacology ; Peroxidases/biosynthesis ; Peroxiredoxins ; Proteomics/methods ; Virus Replication/drug effects ; }, abstract = {In the US, the increase in methamphetamine (METH) use has been associated with increased human immunodeficiency virus (HIV-1) infection. Dendritic cells (DC) are the first line of defense against HIV-1. DC play a critical role in harboring HIV-1 and facilitate the infection of neighboring T cells. However, the role of METH on HIV-1 infectivity and the expression of the proteome of immature dendritic cells (IDC) has not been elucidated. We hypothesize that METH modulates the expression of a number of proteins by IDC that foster the immunopathogenesis of HIV-1 infection. We utilized LTR amplification, p24 antigen assay and the proteomic method of difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of METH on HIV-1 infectivity (HIV-1 IIIB; CXCR4-tropic, X4 strain) and the proteomic profile of IDC. Our results demonstrate that METH potentiates HIV-1 replication in IDC. Furthermore, METH significantly differentially regulates the expression of several proteins including CXCR3, protein disulfide isomerase, procathepsin B, peroxiredoxin and galectin-1. Identification of unique, METH-induced proteins may help to develop novel markers for diagnostic, preventive and therapeutic targeting in METH using subjects.}, } @article {pmid17356593, year = {2007}, author = {Abudu, EK and Banjo, AA and Izegbu, MC and Agboola, AO and Anunobi, CC and Musa, OA}, title = {Malignant Breast Lessions At Olabisi Onabanjo University Teaching Hospital (O.O.U.T.H), Sagamu-a Histopathological Review.}, journal = {The Nigerian postgraduate medical journal}, volume = {14}, number = {1}, pages = {57-59}, pmid = {17356593}, issn = {1117-1936}, mesh = {*Hospitals, Teaching ; Hospitals, University ; Humans ; Nigeria/epidemiology ; Retrospective Studies ; *Universities ; }, abstract = {Various reports suggest an increasing incidence of breast cancer in Nigeria. The large volume of literature published on the subject of breast cancer bear witness to the interest shown in the subject. We therefore carried out a review of 50 cases of breast cancer recently confirmed histologically by our unit to study their characteristics and compare these with previous reports. A 2- years retrospective review of all histologically diagnosed carcinoma of the breast at Olabisi Onabanjo University Teaching Hospital, Sagamu from 2002-2003 was carried out. The peak age of occurrence was between 40-49 years with mean age of 47.5years. Invasive ductal carcinoma was predominant histologic type in 94% of cases and 72% presented late with advanced disease (Manchester stages 111 and 1V) with dismal prognosis. Surgery was the mainstay of treatment for both early and late disease. To ensure early and prompt detection, presentation and treatment, emphasis should be placed on female education, increasing awareness and encouraging breast self-examination. There is also a need for cancer registration centre in the hospital and a multicentred, controlled study of breast cancer in Nigeria.}, } @article {pmid17348440, year = {2007}, author = {Grenier, J and Soria, JC and Mathieu, MC and Andre, F and Abdelmoula, S and Velasco, V and Morat, L and Besse, B and Dunant, A and Spielmann, M and Delaloge, S}, title = {Differential immunohistochemical and biological profile of squamous cell carcinoma of the breast.}, journal = {Anticancer research}, volume = {27}, number = {1B}, pages = {547-555}, pmid = {17348440}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alphapapillomavirus/genetics ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology/virology ; Carcinoma, Ductal, Breast/metabolism/*pathology/virology ; Carcinoma, Squamous Cell/metabolism/*pathology/virology ; Cohort Studies ; DNA-Binding Proteins/analysis ; ErbB Receptors/analysis ; Female ; Humans ; Immunohistochemistry ; Keratin-5/analysis ; Keratin-6/analysis ; Ki-67 Antigen/analysis ; Middle Aged ; Papillomavirus Infections/metabolism/pathology/virology ; Polymerase Chain Reaction ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; Trans-Activators/analysis ; Transcription Factors ; Tumor Suppressor Proteins/analysis ; }, abstract = {BACKGROUND: Pure or metaplastic squamous cell carcinoma (SCC) of the breast is a rare entity with an unclear pathogeny and aggressive clinical behaviour. An attempt was made to characterize its differential immunohistochemical and biological profile.

PATIENTS AND METHODS: Twenty-seven cases of SCC (pure or not) of the breast were matched with 27 ductal invasive carcinomas (IDC) for age, tumour size, nodal involvement and year of diagnosis. The expression levels of oestrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), HER2, Cyclin Bl, hTERT, cytokeratins (CK) 5/6 and p63 were determined immunohistochemically in both cohorts. The presence of the human papilloma virus (HPV) genome was investigated by polymerase chain reaction (PCR).

RESULTS: Pure and metaplastic SCC displayed common profiles typifying a basal origin: they never expressed ER or PR, were HER2-negative in 93% of cases, exhibited positivity for CK5/6 or EGF-R in 75% and 85%, and for p63 in 70% of cases and were highly proliferative. These profiles were markedly different from those of matched controls (p<0.001 for five markers) except for HER2 and hTERT. The HPVgenome was detected in 2 out of 14 cases (14%) of SCC.

CONCLUSION: The expression profile of SCC of the breast was markedly different from that of IDC. A typical "basal-like" phenotype was displayed that may explain part of their behaviour and justify specific therapeutic approaches. HPV infection was not a leading oncogenic event in SCC of the breast.}, } @article {pmid17327649, year = {2007}, author = {Samani, A and Zubovits, J and Plewes, D}, title = {Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples.}, journal = {Physics in medicine and biology}, volume = {52}, number = {6}, pages = {1565-1576}, doi = {10.1088/0031-9155/52/6/002}, pmid = {17327649}, issn = {0031-9155}, mesh = {Biomechanical Phenomena ; Biopsy ; Breast/*pathology ; Breast Diseases/diagnosis/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/pathology ; Computer Simulation ; Elasticity ; Equipment Design ; Humans ; Mammography/*methods ; Radiographic Image Interpretation, Computer-Assisted ; }, abstract = {Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.}, } @article {pmid17325062, year = {2007}, author = {Harvey, JA}, title = {Unusual breast cancers: useful clues to expanding the differential diagnosis.}, journal = {Radiology}, volume = {242}, number = {3}, pages = {683-694}, doi = {10.1148/radiol.2423051631}, pmid = {17325062}, issn = {0033-8419}, mesh = {Biopsy/methods ; Breast Neoplasms/*classification/*diagnosis ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; }, abstract = {Invasive ductal carcinoma and ductal carcinoma in situ account for about 85% of breast cancers. Unusual breast neoplasms may be broadly divided into invasive lobular carcinoma, well-differentiated subtypes of invasive ductal carcinoma, cancers of stromal origin, and metastatic neoplasms. Clues are often present in imaging characteristics, patient demographics, and/or clinical features that may suggest that the finding is not the usual type of breast cancer. Some rare malignancies also provide specific clues to their diagnosis. This review provides an overview of unusual and a few rare malignant breast neoplasms, highlighting particular or specific clinical or imaging findings that will enable residents to expand their differential diagnosis of breast lesions beyond invasive ductal carcinoma.}, } @article {pmid17319852, year = {2007}, author = {Hanna, W and Nofech-Mozes, S and Kahn, HJ}, title = {Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event.}, journal = {The breast journal}, volume = {13}, number = {2}, pages = {122-129}, doi = {10.1111/j.1524-4741.2007.00396.x}, pmid = {17319852}, issn = {1075-122X}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Female ; *Genes, erbB-2 ; *Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization/methods ; Receptor, ErbB-2/*genetics ; }, abstract = {HER2/neu is overexpressed in about 20% of invasive breast carcinomas. Numerous studies have shown that there is high level of concordance between the HER2/neu status of the primary breast cancer and the metastases of a given patient. Recently, changes in HER2/neu status with tumor progression have been reported, suggesting the possibility of an emerging different tumor clone. Little is known about intratumoral heterogeneity with regard to HER2/neu oncoprotein overexpression. We identified nine cases of invasive ductal carcinoma that showed intratumoral variation in HER2/neu oncoprotein expression by immunohistochemistry. This was confirmed by the intratumoral variation in the amplification status of the HER2/neu gene by fluorescence in situ hybridization and by chromogenic in situ hybridization. The results of this study suggest that some cases of primary breast carcinoma are heterogeneous in regard to HER2/neu gene amplification or protein overexpression. Heterogeneity of HER2/neu status in a tumor may be a rare event or underestimated. This phenomenon should be examined as it may contribute to a better understanding of the variation in therapeutic responses and the conflicting data in studies about the prognostic and predictive role of HER2/neu status in subsets of breast cancer patients.}, } @article {pmid17317933, year = {2006}, author = {Naito, Y and Kinoshita, H and Okabe, Y and Kawahara, R and Sakai, T and Suga, H and Arikawa, S and Oshima, K and Kojiro, M}, title = {CD56 (NCAM) expression in pancreatic carcinoma and the surrounding pancreatic tissue.}, journal = {The Kurume medical journal}, volume = {53}, number = {3-4}, pages = {59-62}, doi = {10.2739/kurumemedj.53.59}, pmid = {17317933}, issn = {0023-5679}, mesh = {CD56 Antigen/*analysis ; Humans ; Immunohistochemistry ; Pancreas/*chemistry ; Pancreatic Neoplasms/*chemistry/pathology ; }, abstract = {Expression of CD56, also known as the neural cell adhesion molecule (NCAM), in the pancreatic ducts of chronic pancreatitis is considered to represent a regenerative process of the pancreatic duct system. CD56 expression was analyzed in 25 tissue samples of invasive ductal carcinoma without mixed ductal-endocrine carcinoma of the pancreas, and in the surrounding non-cancerous pancreatic tissue. CD56 expression was detected in intercalated ducts (ICDs) of lobules in the pancreatic parenchyma showing chronic inflammation close to the carcinoma, but not in the carcinoma itself, in all cases. CD56 showed strong, diffuse expression in the areas with severe inflammation, but expression was weak in ICDs where the inflammation was mild. We suggested that CD56 expression is degenerative process in pancreatic tissue with chronic inflammation, and that examination of CD56 expression may be helpful in the differentiation of atypical degenerative ducts from cancerous ducts.}, } @article {pmid17316413, year = {2007}, author = {Millar, EK and Tran, K and Marr, P and Graham, PH}, title = {p27KIP-1, cyclin A and cyclin D1 protein expression in ductal carcinoma in situ of the breast: p27KIP-1 correlates with hormone receptor status but not with local recurrence.}, journal = {Pathology international}, volume = {57}, number = {4}, pages = {183-189}, doi = {10.1111/j.1440-1827.2007.02079.x}, pmid = {17316413}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cyclin A/genetics/*metabolism ; Cyclin D1/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p27/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; }, abstract = {Using whole sections of formalin-fixed paraffin-embedded material the expression of p27(KIP-1), cyclin A and cyclin D1 was examined in 60 cases of ductal carcinoma in situ (DCIS) using routine immunohistochemistry with a median follow up of 95 months (range 10-139 months) to identify any association with disease recurrence. Fifty-six patients were treated by local excision and radiotherapy and four by mastectomy without radiotherapy. There was a highly significant positive association between p27(KIP-1) and estrogen receptor/progesterone receptor (ER/PR) status (P = 0.002, P = 0.02) and with p27(KIP-1) and cyclin D1 expression (P = 0.002). A trend between cyclin A and PR status (P = 0.08) was also identified. These findings mirror those described in invasive ductal carcinoma, but there were no associations of any biomarker with histological parameters such as nuclear grade or with local recurrence on univariate analysis, which was present in four of the 56 locally excised group (7.1%). Further examination of a larger cohort may be worthwhile to explore the possible role as adjunctive predictive markers to aid clinical decision making.}, } @article {pmid17314521, year = {2007}, author = {Rebbapragada, A and Wachihi, C and Pettengell, C and Sunderji, S and Huibner, S and Jaoko, W and Ball, B and Fowke, K and Mazzulli, T and Plummer, FA and Kaul, R}, title = {Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract.}, journal = {AIDS (London, England)}, volume = {21}, number = {5}, pages = {589-598}, doi = {10.1097/QAD.0b013e328012b896}, pmid = {17314521}, issn = {0269-9370}, mesh = {Adult ; Cervix Uteri/immunology/virology ; Chronic Disease ; Cross-Sectional Studies ; Dendritic Cells/immunology ; Female ; Genitalia, Female/*immunology/virology ; HIV Infections/complications/*immunology/transmission/virology ; HIV-1/*isolation & purification ; Herpes Genitalis/complications/*immunology/transmission/virology ; Humans ; Immunity, Mucosal ; Middle Aged ; Mucous Membrane/immunology ; Sex Work ; T-Lymphocyte Subsets/immunology ; Vagina/immunology/virology ; Virus Shedding/immunology ; }, abstract = {OBJECTIVE: There is substantial epidemiological evidence that infection by Herpes simplex virus type 2 (HSV2) enhances both HIV susceptibility and subsequent sexual transmission. Both infections are extremely common in female sex workers (FSWs) in sub-Saharan Africa, and up to 80% of new HIV infections in urban men in the region are acquired via transactional sex. The present study aimed to elucidate the mucosal immune interactions between HIV and HSV2 in the genital tract.

METHODS: Endocervical immune cell populations, cytokine/chemokine protein levels in cervico-vaginal secretions and cervical immune gene expression profiles were measured in a well-defined cohort of HIV-infected and uninfected Kenyan FSWs. Associations between the genital immune milieu and infection by and/or shedding of common genital co-pathogens were examined.

RESULTS: HIV-infected FSWs were much more likely to be infected by HSV2, and to shed HSV2 DNA in the genital tract. There was also a profound negative 'mucosal synergy' between these viruses. In HIV uninfected FSWs, HSV2 infection was associated with a ten-fold increase in cervical immature dendritic cells (iDC) expressing DC-SIGN, and a three-fold increase in cervical CD4+ T cells expressing CCR5. HIV infection was associated with iDC depletion in the cervix, and with increased HSV2 genital reactivation, which in turn was associated with HIV shedding levels.

CONCLUSIONS: The findings suggest a mucosal vicious circle in which HSV2 infection increases HIV target cells in the genital mucosa, subsequent HIV infection impairs HSV2 mucosal immune control, and local HSV2 reactivation enhances both HSV2 and HIV transmission.}, } @article {pmid17309600, year = {2007}, author = {Toya, H and Oyama, T and Ohwada, S and Togo, N and Sakamoto, I and Horiguchi, J and Koibuchi, Y and Adachi, S and Jigami, T and Nakajima, T and Akiyama, T}, title = {Immunohistochemical expression of the beta-catenin-interacting protein B9L is associated with histological high nuclear grade and immunohistochemical ErbB2/HER-2 expression in breast cancers.}, journal = {Cancer science}, volume = {98}, number = {4}, pages = {484-490}, doi = {10.1111/j.1349-7006.2007.00430.x}, pmid = {17309600}, issn = {1347-9032}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Intraductal, Noninfiltrating/*metabolism ; DNA-Binding Proteins/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Receptor, ErbB-2/*metabolism ; Transcription Factors/*metabolism ; beta Catenin/metabolism ; }, abstract = {B9L/BCL9-2, a novel beta-catenin-interacting protein, plays an important role in colorectal carcinogenesis by translocating beta-catenin to the nucleus and enhancing beta-catenin-T-cell factor-mediated transcription. To elucidate the role of B9L in breast cancers, we studied B9L expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast immunohistochemically and compared it to the immunohistochemical expression of known proteins involved in breast carcinogenesis. In breast tissues, B9L immunoreactivity was present exclusively in the nuclei of normal and neoplastic ductal cells. In DCIS, immunohistochemical B9L expression was significantly associated with the tumor nuclear grade, comedo necrosis and the expression of ErbB2/HER-2, c-myc and p53. In IDC, B9L expression was correlated with ErbB2/HER-2 expression and tumor nuclear grade only. In both DCIS and IDC, immunohistochemical B9L expression was not related to the expression of cytoplasmic beta-catenin. We demonstrated that nuclear B9L expression was closely associated with the high nuclear grade cancer phenotype and the expression of ErbB2/HER-2 in breast cancers.}, } @article {pmid17306707, year = {2007}, author = {Takemoto, Y and Hozumi, T and Sugioka, K and Takagi, Y and Matsumura, Y and Yoshiyama, M and Abraham, TP and Yoshikawa, J}, title = {Beta-blocker therapy induces ventricular resynchronization in dilated cardiomyopathy with narrow QRS complex.}, journal = {Journal of the American College of Cardiology}, volume = {49}, number = {7}, pages = {778-783}, doi = {10.1016/j.jacc.2006.05.081}, pmid = {17306707}, issn = {1558-3597}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Blood Pressure/drug effects ; Carbazoles/therapeutic use ; Cardiomyopathy, Dilated/diagnosis/*drug therapy ; Carvedilol ; Echocardiography, Doppler ; Electrocardiography ; Female ; Heart Rate/drug effects ; Humans ; Male ; Middle Aged ; Propanolamines/therapeutic use ; Reference Values ; Ventricular Function/*drug effects ; }, abstract = {OBJECTIVES: We sought to evaluate the effects of beta-blocker therapy on regional and global myocardial mechanics in addition to ventricular synchrony in patients with heart failure and normal QRS by using tissue Doppler and strain echocardiography.

BACKGROUND: It is unknown whether beta-blocker therapy can influence mechanical synchrony.

METHODS: Conventional and strain echocardiography were performed in 15 healthy age-matched volunteers and in 25 patients with idiopathic dilated cardiomyopathy (IDC). Of these, 15 IDC patients on standard heart failure therapy were studied prior to and at 1 and 6 months after initiation of carvedilol therapy and compared to the controls.

RESULTS: There was significant mechanical dyssynchrony in IDC compared with control patients. Patients placed on carvedilol demonstrated a significant decrease in the inferoseptal to lateral wall delay in peak strain (normalized to the R-R interval) between baseline and 1 month and between baseline and 6 months. Similarly, global time to peak segmental strain (455 +/- 51 ms vs. 423 +/- 59 ms, respectively, p = 0.02, and 455 +/- 51 ms vs. 415 +/- 50 ms, respectively, p = 0.01) and the coefficient of variation of the time to peak segmental strain decreased (17 +/- 4% vs. 15 +/- 5%, respectively, p = 0.02, and 17 +/- 4% vs. 14 +/- 5%, respectively, p = 0.03), from baseline to 1 month and between baseline and 6 months, respectively. Global strain significantly increased from baseline to 1 month (-8.2 +/- 1.8 to -10.4 +/- 3.9, respectively, p = 0.01) and between baseline and 6 months (-8.2 +/- 1.8% to -12.0 +/- 3.2%, respectively, p = 0.008). Improvements in left ventricular ejection fraction and reverse remodeling were coincident with reductions in mechanical dyssynchrony.

CONCLUSIONS: The use of carvedilol improves contractile function and dyssynchrony in heart failure patients with normal QRS.}, } @article {pmid17291532, year = {2007}, author = {de Roos, MA and de Bock, GH and de Vries, J and van der Vegt, B and Wesseling, J}, title = {p53 overexpression is a predictor of local recurrence after treatment for both in situ and invasive ductal carcinoma of the breast.}, journal = {The Journal of surgical research}, volume = {140}, number = {1}, pages = {109-114}, doi = {10.1016/j.jss.2006.10.045}, pmid = {17291532}, issn = {0022-4804}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/drug therapy/*pathology/physiopathology ; Carcinoma in Situ/drug therapy/*pathology/physiopathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology/physiopathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local/*pathology/physiopathology ; Predictive Value of Tests ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: Several biological markers have been related to prognosis in mammary ductal carcinoma. The aim of the study was to determine biological markers that could predict local recurrence following treatment for all stages of primary operable ductal carcinoma of the breast.

MATERIALS AND METHODS: A consecutive series of patients treated for pure ductal carcinoma in situ (DCIS, n = 110) and invasive ductal carcinoma (IDC, n = 243) was studied. Twenty-three patients with DCIS were excluded because of lack of original paraffin embedded tissue. All patients had been treated between July 1996 and December 2001. Median follow-up was 49.8 mo. From the original paraffin embedded tumors, tissue microarrays (TMAs) were constructed. On these TMAs, immunohistochemistry was performed for estrogen-receptor (ER), progesterone-receptor (PR), Her2/neu, p53, and cyclin D1. Main outcome was the event of LR. All analyses were stratified for diagnosis (DCIS or IDC) and pathological grade.

RESULTS: In univariate analyses, Her2/neu overexpression (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.1-8.7, P = 0.032) and p53 overexpression (HR 3.5, 95% CI 1.3-9.3, P = 0.014) were associated with LR in patients treated for both DCIS and IDC. In multivariate analysis, p53 overexpression (HR 3.0, 95% CI 1.1-8.2, P = 0.036 and HR 4.4, 95% CI 1.5-12.9, P = 0.008) and adjuvant radiotherapy (HR 0.2, 95% CI 0.1-0.8, P = 0.026) were independent common predictors of LR in patients who had received treatment for both DCIS and IDC.

CONCLUSIONS: p53 overexpression is a common predictor of LR following treatment for all stages of primary operable ductal carcinoma of the breast. This marker may help in planning optimal treatment and follow-up.}, } @article {pmid17290405, year = {2007}, author = {Nielsen, BS and Rank, F and Illemann, M and Lund, LR and Danø, K}, title = {Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor.}, journal = {International journal of cancer}, volume = {120}, number = {10}, pages = {2086-2095}, doi = {10.1002/ijc.22340}, pmid = {17290405}, issn = {0020-7136}, mesh = {Breast Neoplasms/enzymology/genetics/*metabolism/*pathology ; Carcinoma in Situ/enzymology/genetics/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics/metabolism/*pathology ; Fluorescent Antibody Technique/methods ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Matrix Metalloproteinase 13/metabolism ; RNA, Messenger/biosynthesis/genetics ; Receptors, Cell Surface/*biosynthesis/metabolism ; Receptors, Urokinase Plasminogen Activator ; Stromal Cells/enzymology/metabolism/pathology ; Urokinase-Type Plasminogen Activator/*biosynthesis/genetics/metabolism ; }, abstract = {The transition from ductal carcinoma in situ (DCIS) of the breast to invasive ductal carcinoma is facilitated by proteolytic degradation of basement membrane. The transition can be identified as microinvasive foci in a small proportion of DCIS lesions. We have previously found that MMP-13 is frequently expressed in such foci. To establish whether plasmin-directed proteolysis is likely to be involved in early invasion, we have here studied the expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) in human DCIS lesions with and without microinvasion. uPA mRNA was detected in periductal stromal cells in all of 9 DCIS lesions with microinvasion and in 2 of 9 DCIS lesions without microinvasion by in situ hybridization. The uPA mRNA signal was seen in numerous stromal cells in microinvasive areas together with MMP-13 mRNA expressing cells. Double immunofluorescence analyses, using emission fingerprinting, showed that the uPA expressing stromal cells included both myofibroblasts and macrophages. The early invasive carcinoma cells were negative for uPA. uPAR immunoreactivity was focally upregulated in periductal stromal cells in all of the 9 DCIS lesions with microinvasion and in only 2 of the 9 DCIS lesions without microinvasion. uPAR was seen in both macrophages and myofibroblasts in microinvasive areas, and it was evident that uPA and uPAR colocalized in both fibroblast-like cells and macrophage-like cells. We conclude that periductal macrophages and myofibroblasts are strongly involved in the initial steps of breast cancer invasion by focally upregulating the expression of the plasminogen activation system and MMP-13.}, } @article {pmid17288765, year = {2006}, author = {Huang, J and Zheng, Z and Hu, SS and Yang, YJ and Zhao, H and Song, LF and Song, YH and Zhu, J and Zhao, SH}, title = {[Comparison between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {34}, number = {11}, pages = {1005-1008}, pmid = {17288765}, issn = {0253-3758}, mesh = {Adolescent ; Adult ; Cardiomyopathy, Dilated/*diagnosis/pathology/surgery ; Heart Failure/diagnosis/pathology ; *Heart Transplantation ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Stroke Volume ; }, abstract = {OBJECTIVE: To evaluate the discrepancy between pre- and post-transplant diagnosis of end-stage dilated cardiomyopathy, a pre-transplantation diagnosis was compared with the diagnosis made after macroscopic and microscopic examination of the explanted hearts in 40 cardiac transplant recipients who had undergone cardiac transplantation at our institute.

METHODS: Pre-operation echocardiograms were obtained in all patients and coronary angiogram was obtained in 9 patients who had significant risk factors for coronary heart disease (CHD). CHD was considered present when there was a 75% reduction in cross-sectional luminal area of >or= 1 major coronary artery. Idiopathic dilated cardiomyopathy (IDC) was diagnosed when ventricular dilation and global reduction in ventricular systolic function were present in the absence of any identifiable cause. IDC patients with an alcohol consumption of > 100 g/day during the last 12 months before the onset of congestive heart failure were classified as having alcoholic cardiomyopathy. The pathological diagnosis of arrhythmogenic right ventricular cardiomyopathy was formulated in the presence of gross/or histological evidence of regional or diffuse transmural fatty or fibrofatty infiltration of the right ventricular free wall.

RESULTS: Before transplantation, 45.0%, 17.5%, 17.5% and 7.5% of patients were classified as IDC, CHD, alcoholic cardiomyopathy and hypertrophic cardiomyopathy. Post-transplant CHD diagnosis was made in all patients with a pre-transplant diagnosis of CHD. Post-transplant CHD diagnosis was also established in 4 patients with a pre-transplant diagnosis of IDC, in 4 patients with presumptive alcoholic cardiomyopathy, in 1 patient with hypertensive cardiomyopathy and in 1 patient with a pre-transplant diagnosis of aortic valve disease. Post-transplant arrhythmogenic right ventricular cardiomyopathy diagnosis was made in 6 patients with a pre-transplant diagnosis of IDC or KaShan disease. Post-transplant giant cell myocarditis diagnosis was made in 1 patient with a pre-transplant diagnosis of IDC.

CONCLUSION: Post-transplant CHD diagnosis is significantly higher than that of pre-transplant (42.5% vs. 17.5%, P < 0.05). Part of these patients might benefit from bypass surgery or PCI. Therefore, "in-depth" search for a heart failure cause, especially the coronary angiography examination, should be conducted in all heart transplantation candidates due to heart failure, regardless of their clinical presentation.}, } @article {pmid17283573, year = {2007}, author = {Rampey, AM and Lathers, DM and Woodworth, BA and Schlosser, RJ}, title = {Immunolocalization of dendritic cells and pattern recognition receptors in chronic rhinosinusitis.}, journal = {American journal of rhinology}, volume = {21}, number = {1}, pages = {117-121}, doi = {10.2500/ajr.2007.21.2998}, pmid = {17283573}, issn = {1050-6586}, mesh = {Biomarkers/metabolism ; Biopsy ; Chronic Disease ; Dendritic Cells/immunology/*pathology ; Humans ; Immunohistochemistry ; Receptors, Pattern Recognition/*metabolism ; Rhinitis/complications/*immunology/pathology ; Sinusitis/*immunology/pathology ; }, abstract = {BACKGROUND: Dendritic cell (DC) activation and antigen presentation to T cells are critical to innate and adaptive immunity. Toll-like receptors (TLRs) are known to bind pathogen-associated molecular patterns in addition to sinonasally secreted surfactant proteins (SP) such as SP-A and SP-D. TLR binding is known to activate DCs. Based on these observations, we sought to establish the presence, in sinonasal mucosa, of DC and the pattern recognition receptors (PRRs), CD14, TLR2, and TLR4.

METHODS: Sinonasal biopsy specimens were taken from patients with eosinophilic nonatopic nasal polyposis (n = 4), allergic fungal sinusitis (n = 1), and nondiseased patients undergoing cerebrospinal fluid leak repair or pituitary tumor resection (n = 2). Tissue samples were stained immunohistochemically for PRR (CD14, TLR2, and TLR4), mature DC marker (CD208), iDC marker (CD209), or isotype controls.

RESULTS: Immature and mature DC were immunolocalized to the subepithelial stroma and ciliated epithelial surface, respectively. Diffuse staining of CD14 was observed throughout the stroma with additional staining in the ciliated epithelium. The TLR markers showed no staining in the ciliated epithelium. TLR2 primarily localized in stroma immediately deep to the ciliated epithelial surface. TLR4 immunolocalized to submucosal seromucinous gland ductal epithelium. Data from nondiseased patients were mixed, with one patient showing minimal staining of any of the tested cellular markers.

CONCLUSION: This study indicates progressive DC activation and emigration of mature antigen-presenting cells from the epithelial surfaces of sinonasal mucosa. The presence of TLR known to bind SP-A and SP-D suggests a link between SP expression and immune response in sinonasal mucosa.}, } @article {pmid17281269, year = {2005}, author = {Palacios, M and Vallverdu, M and Hoyer, D and Friedrich, H and Bayes de Luna, A and Caminal, P}, title = {Hidden markov models and mutual information analysis to characterize nonlinear dynamics in heart rate variability.}, journal = {Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference}, volume = {2005}, number = {}, pages = {4618-4621}, doi = {10.1109/IEMBS.2005.1615499}, pmid = {17281269}, issn = {1557-170X}, abstract = {A study of nonlinear dynamics of the heart rate variability (HRV) was performed using hidden Markov models (HMM) and Mutual Information (MI). A methodology based on HMM has been developed in the present work. Cardiac RR series were analyzed in the three frequency bands: HF (0.15-0.45Hz), high frequency band; LF (0.04-0.15Hz), low frequency band; VLF (0.003-0.04Hz), very low frequency band. These series (0, observations) were modeled using HMM. The model λ=(A,B,∏) was selected so that P(O/λ) was locally maximized. Ergodic topology and N=10 states were also considered for this analysis. Different measures based on HMM were defined and obtained from RR time series of 37 Idiopathic Dilated Crdiomyopathy (IDC) patients and 46 healthy subjects (NRM), during awake and sleep stages. Two groups of IDC patients were considered: 11 high risk (HR) patients, after aborted sudden cardiac death (SCD) or who died during the follow up; 26 low risk (LR) patients, without SCD. Some HMM measures showed high percentages (up to 100%) of well classified subjects in all groups.}, } @article {pmid17277766, year = {2007}, author = {Iwaya, K and Norio, K and Mukai, K}, title = {Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {20}, number = {3}, pages = {339-343}, doi = {10.1038/modpathol.3800741}, pmid = {17277766}, issn = {0893-3952}, mesh = {Actin-Related Protein 2/*biosynthesis ; Breast Neoplasms/*metabolism/mortality/*pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis/pathology ; Prognosis ; Wiskott-Aldrich Syndrome Protein Family/*biosynthesis ; }, abstract = {Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the breast.}, } @article {pmid17266026, year = {2007}, author = {Tait, LR and Pauley, RJ and Santner, SJ and Heppner, GH and Heng, HH and Rak, JW and Miller, FR}, title = {Dynamic stromal-epithelial interactions during progression of MCF10DCIS.com xenografts.}, journal = {International journal of cancer}, volume = {120}, number = {10}, pages = {2127-2134}, doi = {10.1002/ijc.22572}, pmid = {17266026}, issn = {0020-7136}, support = {R03 CA 94333/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cell Communication/*physiology ; Disease Progression ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Mice, SCID ; Protein Biosynthesis ; Receptors, CXCR4/biosynthesis ; Stromal Cells/metabolism/pathology ; Transforming Growth Factor beta1/biosynthesis ; Transplantation, Heterologous ; }, abstract = {MCF10DCIS.com cells form comedo type ductal carcinoma in situ in immune-deficient mice before forming invasive ductal carcinoma. As the lesions mature, both stromal and epithelial cells undergo phenotypic changes detected by immunohistochemistry. Myofibroblasts are present before the formation of carcinoma in situ and after development of invasive carcinoma. MCF10DCIS. com lesions develop a myoepithelial layer prior to exhibiting a basement membrane surrounding the ductal mass. TGFbeta1 is initially expressed by the epithelial cells but is expressed by stroma in invasive carcinoma. Stromal derived factor-1 is detected in epithelial cells in early carcinoma in situ but is produced in stromal cells in invasive carcinoma. The receptor CXCR4 is expressed by epithelial cells in the xenografts at all times, as is the hepatocyte growth factor receptor c-met. MCF10DCIS.com xenografts illustrate the dynamic interplay of epithelium and stroma in the development of carcinoma in situ and subsequent invasive carcinoma. Although the phenotype of the epithelial cells may be dependent upon the stroma, the malignant epithelium induces the development of the stroma necessary for progression to the invasive stage. (c) 2007 Wiley-Liss, Inc.}, } @article {pmid17265021, year = {2007}, author = {Bergmann, C and Strauss, L and Zeidler, R and Lang, S and Whiteside, TL}, title = {Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {56}, number = {9}, pages = {1429-1442}, doi = {10.1007/s00262-007-0280-9}, pmid = {17265021}, issn = {0340-7004}, support = {P0-1 DE12321/DE/NIDCR NIH HHS/United States ; }, mesh = {*Carcinoma, Squamous Cell/immunology ; Cell Line, Tumor ; Cell Proliferation ; Coculture Techniques ; Cytokines/metabolism/pharmacology ; Dendritic Cells/immunology ; Enzyme-Linked Immunosorbent Assay ; *Head and Neck Neoplasms/immunology ; Humans ; *Interleukin-10 ; *Lymphocyte Activation ; Sirolimus/pharmacology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; }, abstract = {OBJECTIVE: Chronic inflammation and cancer development are associated with dysregulated immune responses and the presence of regulatory T cells (T(reg)). To study the role of T(reg) in tumor cell escape from immune surveillance, an in vitro model simulating the tumor microenvironment and promoting the induction and expansion of IL-10(+) T(reg)type 1 (Tr1) was established.

METHODS: An in vitro co-culture system (IVA) included an irradiated head and neck squamous cell carcinoma cell line, immature dendritic cells (iDC), CD4(+)CD25(-)T cells and cytokines, IL-2 (10 IU/ml), IL-10 (20 IU/ml), IL-15 (20 IU/ml) +/- 1 nM rapamycin. Autologous iDC and CD4(+)CD25(-) T cells were obtained from the peripheral blood of 15 normal donors. Co-cultures were expanded for 10 days. Proliferating lymphocytes were phenotyped by multi-color flow cytometry. Their suppressor function was measured in CFSE inhibition assays +/- neutralizing anti-IL-10 mAb and using transwell cultures. Culture supernatants were tested for IL-4, IL-10, TGF-beta and IFN-gamma in ELISA.

RESULTS: In the IVA, low doses of IL-2, IL-10 and IL-15 promoted induction and expansion of CD3(+)CD4(+)CD25(-)IL2Rbeta(+)IL2Rgamma(+)FoxP3(+)CTLA-4(+)IL-10(+) cells with suppressor activity (mean suppression +/- SD = 58 +/- 12%). These suppressor cells produced IL-10 (mean +/- SD = 535 +/- 12 pg/ml) and TGF-beta (mean +/- SD = 512 +/- 38 pg/ml), but no IL-4 or IFN-gamma. Suppressor function of co-cultures correlated with the percent of expanding IL-10(+) Tr1 cells (r (2)=()0.9; P < 0.001). The addition of rapamycin enriched Tr1 cells in all co-cultures. Neutralizing anti-IL-10 mAb abolished suppressive activity. Suppression was cell-contact independent.

CONCLUSION: The tumor microenvironment promotes generation of Tr1 cells which have the phenotype distinct from that of CD4(+)CD25(high)FoxP3(+) nTreg and mediate IL-10 dependent immune suppression in a cell-contact independent manner. Tr1 cells may play a critical role in cancer progression.}, } @article {pmid17239264, year = {2006}, author = {Gonzalez-Angulo, AM and Sahin, A and Krishnamurthy, S and Yang, Y and Kau, SW and Hortobagyi, GN and Cristofanilli, M}, title = {Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma.}, journal = {Clinical breast cancer}, volume = {7}, number = {5}, pages = {396-400}, doi = {10.3816/CBC.2006.n.056}, pmid = {17239264}, issn = {1526-8209}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal/*metabolism ; Carcinoma, Lobular/*metabolism ; Cell Adhesion Molecules/metabolism ; Female ; Humans ; Hyaluronan Receptors/metabolism ; Integrin alpha6/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Steroid/analysis ; Retrospective Studies ; }, abstract = {PURPOSE: The objective of this study was to compare the differential expression of established histopathologic and biologic markers of proliferation, apoptosis, and angiogenesis in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in a group of axillary node-negative breast cancers.

PATIENTS AND METHODS: Two hundred twenty patients with axillary node-negative ILC and IDC who underwent surgery at the University of Texas M. D. Anderson Cancer Center between 1978 and 1995 had tissue available for analysis. Of these, 206 (94%) had IDC and 14 (6%) had ILC. Estrogen receptors, progesterone receptors, tumor and stromal expression of vascular endothelial growth factor receptor 2, CD44, laminin-5, E-cadherin, and topoisomerase-2 were evaluated by immunohistochemical analysis. HER2/neu and alpha6beta4 integrin were evaluated by in situ hybridization. The Fisher exact test was used to calculate significant differences between ILC and IDC. Median age was 59 years.

RESULTS: Invasive lobular carcinoma was more likely to occur in patients aged > 50 years. Invasive lobular carcinoma tended to be > 2 cm (50% vs. 39%), have a nuclear grade of 1/2 (100% vs. 72%), be estrogen receptor positive (93% vs. 70%), HER2/neu negative (92% vs. 68%), have high CD44 expression (31% vs. 16%), low stromal vascular endothelial growth factor receptor 2 expression (36% vs. 47%), no E-cadherin expression (0 vs. 90%), and low laminin-5 expression (15% vs. 25%), compared with IDC.

CONCLUSION: Invasive lobular carcinoma and IDC might be distinct histologic types of breast cancer with different expression of biologic markers. These differences, not all being statistically significant in this small study, might generate hypotheses to develop tailored options for future systemic therapy.}, } @article {pmid17237134, year = {2007}, author = {Neglia, D and De Maria, R and Masi, S and Gallopin, M and Pisani, P and Pardini, S and Gavazzi, A and L'abbate, A and Parodi, O}, title = {Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy.}, journal = {Heart (British Cardiac Society)}, volume = {93}, number = {7}, pages = {808-813}, pmid = {17237134}, issn = {1468-201X}, mesh = {Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/*drug therapy/physiopathology ; Carvedilol ; Coronary Circulation/*drug effects ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Propanolamines/*therapeutic use ; Vasodilator Agents/*therapeutic use ; Ventricular Dysfunction, Left/physiopathology ; }, abstract = {OBJECTIVE: To assess whether chronic treatment with carvedilol can increase myocardial blood flow (MBF) and MBF reserve in idiopathic dilated cardiomyopathy (IDC).

STUDY DESIGN: In a double-blind, placebo-controlled trial, 16 consecutive patients with IDC were randomised to treatment with either carvedilol up to 25 mg twice a day (n = 8, 7 men, mean (SD) age 60 (9) years, mean (SD) left ventricular ejection fraction (LVEF) 30% (5%)), or placebo (n = 8, 6 men, mean (SD) age 62 (9) years, mean (SD) LVEF 28% (6%), NS vs carvedilol group). Before and 6 months after treatment, regional MBF was measured at rest and after intravenous injection of dipyridamole (Dip; 0.56 mg/kg in 4 min) by positron emission tomography and using (13)N-ammonia as a flow tracer. Exercise capacity was assessed as the time duration in a maximal bicycle exercise stress test.

RESULTS: Carvedilol induced a significant decrease in heart rate at rest and during maximal exercise, and an increase in exercise capacity. Absolute MBF values did not significantly change after carvedilol or placebo treatment, either at rest or during Dip injection, although Dip-MBF tended to improve after treatment. Coronary flow reserve significantly increased following carvedilol treatment (from 1.67 (0.63) to 2.58 (1.04), p<0.001), whereas it remained unchanged following the placebo treatment (from 1.80 (0.84) to 1.77 (0.60), NS). Stress-induced regional perfusion defects decreased after carvedilol treatment (from 38% to 15%).

CONCLUSIONS: Long-term treatment with carvedilol can significantly increase coronary flow reserve and reduce the occurrence of stress-induced perfusion defects, suggesting a favourable effect of the drug on coronary microvascular function in patients with IDC.}, } @article {pmid17236553, year = {2006}, author = {Niu, Y and Wang, Y and Wei, L and Wei, XY and Niu, RF}, title = {[A quantitative immuno-fluorescence analysis of alpha-tubulin and gamma-tubulin proteins in precancerous lesion and carcinoma of the breast and their clinical significance].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {28}, number = {8}, pages = {590-593}, pmid = {17236553}, issn = {0253-3766}, mesh = {Breast/chemistry/pathology ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Cell Differentiation ; Cell Proliferation ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Precancerous Conditions/metabolism/*pathology ; Tubulin/*analysis ; }, abstract = {OBJECTIVE: In order to explore the correlation between the centrosome aberration and oncogenesis of the breast carcinoma, the expression of alpha-tubulin and gamma-tubulin proteins in breast precancerous lesions, ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) was investigated.

METHODS: Quantitative immunofluorescence analysis was performed for measuring centrosome proteins by FITC-labeled monoclonal anti-alpha and anti-gamma-tubulin antibodies in 90 cases with precancerous lesions, DCIS and IDC of the breast, respectively. Normal breast tissue from 30 cases were taken as control group.

RESULTS: The average of positive (FITC-labeled) cells were 3.2, 11.6, 14.8, 23.1 (alpha-tubulin) and 3.3, 10.7, 14.5, 24.5 (gamma-tubulin) in four groups, respectively. There were significant differences of alpha-tubulin or gamma-tubulin expression among those groups (P = 0.000), respectively. The highest expression quantity was in IDC group and the lowest was in normal breast tissue. Their expression was significantly associated with cellular proliferation and differentiation.

CONCLUSION: There is over-expression of the centrosome tubulin protein in the precancerous stage of the breast. The centrosome aberration may play an important role during the crucial early step of oncogenesis and it may promote the cellular cancerization or transformation into malignancy. Quantitative immuno-fluorescence analysis and immunohistochemistry can be complementary each other.}, } @article {pmid17236203, year = {2007}, author = {Ohuchida, K and Mizumoto, K and Ohhashi, S and Yamaguchi, H and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Twist, a novel oncogene, is upregulated in pancreatic cancer: clinical implication of Twist expression in pancreatic juice.}, journal = {International journal of cancer}, volume = {120}, number = {8}, pages = {1634-1640}, doi = {10.1002/ijc.22295}, pmid = {17236203}, issn = {0020-7136}, mesh = {Adenocarcinoma, Mucinous/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Pancreatic Ductal/genetics/metabolism ; Carcinoma, Papillary/genetics/metabolism ; Cells, Cultured ; Epithelial Cells/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Nuclear Proteins/*genetics ; Pancreas/metabolism/pathology ; Pancreatic Juice/*physiology ; Pancreatic Neoplasms/*genetics/metabolism ; Pancreatitis/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Twist-Related Protein 1/*genetics ; Up-Regulation ; }, abstract = {Despite evidence that Twist, a highly conserved basic helix-loop-helix transcription factor, is a novel oncogene, there are no reports describing Twist expression in pancreatic cancer. Intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia (PanIN) are precursor lesions of pancreatic cancer. To clarify involvement of Twist expression in pancreatic cancer, we used quantitative reverse transcription-polymerase chain reaction and examined Twist expression in pancreatic cancer, IPMN, and non-neoplastic pancreas using bulk tissues (11 cancers, 18 IPMNs, and 15 non-neoplastic pancreata), microdissected cells (cancer from 22 sections, IPMN from 19 sections, PanIN from 6 sections, and pancreatitis-affected epithelial cells from 14 sections), and pancreatic juice (16 from cancer, 28 from IPMN, and 17 from pancreatitis). Twist expression differed significantly between cancer and IPMN bulk tissues (p < 0.0001) but not between cancer and non-neoplastic tissues. Twist expressions differed significantly between microdissected cancer cells, IPMN cells, and pancreatitis-affected cells (all comparisons, p < 0.017). PanIN cells expressed significantly lower levels of Twist than did IDC cells (p = 0.016). Twist expression differed significantly between cancer and IPMN juice samples (p = 0.0002) but not between cancer and pancreatitis juice samples. Receiver operation characteristic curve analyses revealed that measurement of Twist was more useful for discriminating cancer from IPMN than from chronic pancreatitis (p = 0.009). Our results suggest that Twist is involved in tumor progression of pancreatic cancer and that measurement of Twist in pancreatic juice may be useful to differentiate pancreatic cancer from nonmalignant neoplasms such as IPMN.}, } @article {pmid17223209, year = {2007}, author = {Miettinen, KH and Magga, J and Vuolteenaho, O and Vanninen, EJ and Punnonen, KR and Ylitalo, K and Tuomainen, P and Peuhkurinen, KJ}, title = {Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.}, journal = {Regulatory peptides}, volume = {140}, number = {3}, pages = {178-184}, doi = {10.1016/j.regpep.2006.12.004}, pmid = {17223209}, issn = {0167-0115}, mesh = {Adult ; Apelin ; Biomarkers/blood ; Cardiomyopathy, Dilated/blood/*diagnosis ; Carrier Proteins/*blood ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*blood ; Interleukin-6/blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Norepinephrine/blood ; Peptide Fragments/blood ; Predictive Value of Tests ; Radioimmunoassay ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.}, } @article {pmid17220675, year = {2007}, author = {Sagara, Y and Rai, Y and Sagara, Y and Tamada, S and Tsuchimochi, S and Takahama, T and Matsuyama, Y and Ando, M and Ooi, Y and Sagara, Y}, title = {[A case of inflammatory breast cancer achieving pathological complete response by primary systemic therapy with CEF (cyclophosphamide, epirubicin, 5-fluorouracil) followed by docetaxel].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {1}, pages = {77-80}, pmid = {17220675}, issn = {0385-0684}, mesh = {Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/radiotherapy/surgery ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Docetaxel ; Drug Administration Schedule ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Inflammation/drug therapy ; Mammography ; Middle Aged ; Remission Induction ; Taxoids/administration & dosage ; Tomography, X-Ray Computed ; Ultrasonography, Mammary ; }, abstract = {A 48-year-old woman noticed her right breast swelling since a few weeks earlier. Rigidity in the AC area, hotness, swelling and peau d'orange appearance of the right whole breast were recognized. She was diagnosed as inflammatory breast cancer clinically and invasive ductal carcinoma with lymphatic invasion pathologically. The patient underwent primary systemic therapy with 4 cycles of CEF (cyclophosphamide 500 mg/m(2), epirubicin 100 mg/m(2), 5-fluorouracil 500 mg/m(2)) followed by 4 cycles of docetaxel (70 mg/m(2)). The effect of chemotherapy showed a partial response evaluated by mammography and ultrasonography, and complete response by MRI before surgery. Right mastectomy with level II lymph node dissection was performed. Pathologically, complete response was confirmed (pCR). Although IBC has been known for its poor outcome, this case suggests IBC will show a better prognosis by chemotherapy such as CEF followed by docetaxel.}, } @article {pmid17220674, year = {2007}, author = {Ohsako, T and Inoue, K and Nagamoto, N and Tanaka, E and Yoshida, Y}, title = {[Locally advanced breast cancer with a good response to sequential endocrine monotherapy--a case report].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {1}, pages = {73-75}, pmid = {17220674}, issn = {0385-0684}, mesh = {Aged, 80 and over ; Anastrozole ; Androstadienes/administration & dosage ; Antineoplastic Agents, Hormonal/*administration & dosage ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Drug Administration Schedule ; Female ; Humans ; Nitriles/administration & dosage ; Remission Induction ; Tamoxifen/*administration & dosage ; Triazoles/administration & dosage ; }, abstract = {An 81-year-old woman with a right breast tumor exposed through the skin surface visited our clinic in June 2004. Pathological findings of the resected tumor specimen indicated invasive ductal carcinoma of the breast,positive ER/PgR status,and negative HER 2/neu status. The enlarged right axillary lymph nodes were palpable. Ultrasonography and computed tomography revealed that the tumor invaded the chest wall without any metastasis to remote organs. On July 5, 2004, we started anastrozole treatment. Its effects were confirmed in the first month,and the treatment was continued for 8 months. Substituting anastrozole with exemestane was not effective. However, the exposed part of the tumor completely responded to tamoxifen that was administered for 2 months. The effect of tamoxifen continued until February 2006, and most of the subcutaneous part of the tumor became nonpalpable. Thus, sequential endocrine monotherapy proved useful for an elderly woman with locally advanced breast cancer.}, } @article {pmid17220672, year = {2007}, author = {Rai, Y and Sagara, Y and Sagara, Y and Takahama, T and Matsuyama, Y and Ando, M and Sagara, Y and Ooi, Y and Inoue, K and Kurosumi, M}, title = {[Preoperative therapy with trastuzumab and paclitaxel in a stage IV advanced breast cancer with complete pathologic response].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {34}, number = {1}, pages = {65-68}, pmid = {17220672}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lymph Node Excision ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/analysis ; Remission Induction ; Trastuzumab ; }, abstract = {A 53-year-old woman had a 105x100 mm tumor on her right breast with a 55x36 mm-sized bleeding ulcer of the skin and ipsilateral axillary and cervical lymph nodes swelling (T4bN3cM1, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor (ER-, PgR-) and overexpression of HER 2 (Hercep Test score 3+). She was treated with weekly trastuzumab (initially 4 mg/kg followed by 2 mg/kg every week), and a combination of tri-weekly paclitaxel (175 mg/m(2), 6 courses). After 3 courses of administration, the breast tumor subsided, the ulcer became flat, and axillary and cervical nodes completely disappeared. Clinical CR was obtained after 6 courses of treatment, and mastectomy with axillary clearance was then performed. Histopathology of the breast and lymph nodes showed complete disappearance of cancer cells (pCR, Grade 3+3 (d) +3 (n)). The combination of trastuzumab and paclitaxel is a promising regimen for HER 2 positive advanced breast cancer.}, } @article {pmid17218854, year = {2007}, author = {Tang, P and Hajdu, SI and Lyman, GH}, title = {Ductal carcinoma in situ: a review of recent advances.}, journal = {Current opinion in obstetrics & gynecology}, volume = {19}, number = {1}, pages = {63-67}, doi = {10.1097/GCO.0b013e3280114a3a}, pmid = {17218854}, issn = {1040-872X}, mesh = {Biomarkers ; Breast Neoplasms/genetics/pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/*therapy ; Female ; Humans ; *Mastectomy, Segmental ; Neoplasm Recurrence, Local/prevention & control ; Prognosis ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent findings on ductal carcinoma in situ of the breast and their impact on prognosis and management of the disease.

RECENT FINDINGS: Great advances have been made in our understanding of ductal carcinoma in situ. Nuclear grading is probably the most important pathological factor that affects clinical outcome and correlates with distinct genetic pathways. Identifying key molecules in each pathway may provide better markers for prognostic, predictive and therapeutic purposes. Not all cases of ductal carcinoma in situ will progress to invasive ductal carcinoma, and identifying this subgroup of patients should lead to a reduction of overtreatment. Progenitor cell theory at the cellular level and sick lobe theory at the architectural level may help provide a better understanding of ductal carcinoma in situ from a different perspective and facilitate the development of individualized therapy. Prevention of local recurrence is the primary goal for treatment. Debate continues, however, on the use of radiotherapy, hormonal therapy, and sentinel lymph node biopsy. A panel of molecular markers may be needed for accurately predicting clinical outcome for the disease.

SUMMARY: Understanding the carcinogenesis of ductal carcinoma in situ at the molecular level may lead to an optimal individualized therapy with minimal over or undertreatment.}, } @article {pmid17218669, year = {2007}, author = {Cameron, ID and Kurrle, S}, title = {Preventing falls in elderly people living in hospitals and care homes.}, journal = {BMJ (Clinical research ed.)}, volume = {334}, number = {7584}, pages = {53-54}, pmid = {17218669}, issn = {1756-1833}, mesh = {Accidental Falls/*prevention & control ; Aged ; Homes for the Aged ; Hospitalization ; Humans ; }, abstract = {Inconclusive evidence means uncertainty remains}, } @article {pmid17218074, year = {2007}, author = {Meeuwis, C and Peters, NH and Mali, WP and Gallardo, AM and van Hillegersberg, R and Schipper, ME and van den Bosch, MA}, title = {Targeting difficult accessible breast lesions: MRI-guided needle localization using a freehand technique in a 3.0 T closed bore magnet.}, journal = {European journal of radiology}, volume = {62}, number = {2}, pages = {283-288}, doi = {10.1016/j.ejrad.2006.12.006}, pmid = {17218074}, issn = {0720-048X}, mesh = {Biopsy, Needle/*methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Contrast Media ; Equipment Design ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Image Enhancement ; Image Interpretation, Computer-Assisted ; Lymphatic Metastasis ; *Magnetic Resonance Imaging/instrumentation/methods ; *Magnetics ; Mastectomy, Segmental ; Middle Aged ; Treatment Outcome ; }, abstract = {PURPOSE: To report the accuracy of magnetic resonance imaging (MRI)-guided needle localization for diagnosis of MRI detected suspicious breast lesions located in difficult accessible regions of the breast, using the freehand method in a 3.0 T closed bore magnet.

MATERIALS AND METHODS: In five patients with five MRI-only breast lesions underwent MRI-guided needle localization for histopathologic evaluation of the lesions. All interventional procedures were performed in a 3.0 T MRI system with the patient in prone position and by using a dedicated phased array breast coil. MRI-guided needle localizations were performed by using a freehand technique. In our study, the high-resolution scan allowed preprocedural localization of all lesions without use of contrast enhancement. In all cases contrast-enhanced MRI was performed after insertion of the wire to confirm the tip of the wire in direct contact with the enhancing lesion.

RESULTS: Needle localizations were performed in five patients. Histopathologic evaluation of tissue after surgery excision biopsy revealed one lymph node, three invasive ductal carcinoma and one ductal carcinoma in situ. Lesion size varied from 6 to 30 mm. Mean duration time was 25 min. No complications occurred during the intervention method. In the patient with the benign lesion control MRI of the breast after 6 months confirmed lesion removal.

CONCLUSIONS: MRI-guided needle localization by using a freehand technique in a 3.0 T closed bore magnet is a safe and accurate method for diagnosis of difficult accessible breast lesions only visible on MRI.}, } @article {pmid17217540, year = {2007}, author = {Fulford, LG and Reis-Filho, JS and Ryder, K and Jones, C and Gillett, CE and Hanby, A and Easton, D and Lakhani, SR}, title = {Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival.}, journal = {Breast cancer research : BCR}, volume = {9}, number = {1}, pages = {R4}, pmid = {17217540}, issn = {1465-542X}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cohort Studies ; Female ; Humans ; Immunohistochemistry ; Keratin-14/analysis/metabolism ; Middle Aged ; *Neoplasm Metastasis ; Prognosis ; Survival Analysis ; }, abstract = {INTRODUCTION: Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas.

METHODS: We performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas with extended clinical follow-up (mean 116 months), and we correlated CK14 immunopositivity (basal-like phenotype) with clinicopathological criteria.

RESULTS: Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01, and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR 1.92, p = 0.051). In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival in CK14-positive and -negative patients was similar at 5 years (60% and 59%, respectively), but the long-term survival was better in CK14-positive patients (HR 0.69, p = 0.02).

CONCLUSION: These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread. Compared to other grade III tumours, basal-like tumours appear to have a relatively good long-term survival but survival after metastases is poor.}, } @article {pmid17217490, year = {2007}, author = {Borg, M and Yeoh, E and Bochner, M and Butters, J and van Doorn, T and Farshid, G and Kollias, J and Kotasek, D and Gill, G and Lim, A and Olver, I and Parnis, F and Rush, G}, title = {Feasibility study on the MammoSite in early-stage breast cancer: initial experience.}, journal = {Australasian radiology}, volume = {51}, number = {1}, pages = {53-61}, doi = {10.1111/j.1440-1673.2006.01659.x}, pmid = {17217490}, issn = {0004-8461}, mesh = {Aged ; Asia ; Australia ; Brachytherapy/*methods ; Breast Neoplasms/pathology/*radiotherapy ; Catheterization ; Feasibility Studies ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Radiotherapy Dosage ; Treatment Outcome ; }, abstract = {The aims of this study were to evaluate the feasibility, practicality, efficacy and safety of the delivery of accelerated partial breast irradiation using the MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0, T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The MammoSite was inserted 20-37 days postoperatively. External beam radiation therapy to the whole breast commenced 1-5 days after accelerated partial breast irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed spontaneously within 3-5 days. No Grade III or higher acute toxicity or local infection was recorded. The ease of insertion and accuracy of dosimetry makes the MammoSite suitable for use in properly selected women with early-stage breast cancer in a trial setting.}, } @article {pmid17213769, year = {2006}, author = {Balu-Maestro, C and Chapellier, C and Ben Taaritt, I and Fournol, M}, title = {[Ultrasound examination of breast microcalcifications: luxury or necessity?].}, journal = {Journal de radiologie}, volume = {87}, number = {12 Pt 1}, pages = {1849-1858}, doi = {10.1016/s0221-0363(06)74165-8}, pmid = {17213769}, issn = {0221-0363}, mesh = {Breast Diseases/*diagnostic imaging ; Calcinosis/*diagnostic imaging ; Humans ; Mammography ; Prospective Studies ; Ultrasonography ; }, abstract = {PURPOSE: Determine the value of ultrasound for the diagnosis of isolated breast microcalcifications.

MATERIAL AND METHODS: Fifty clusters of microcalcifications, including 25 smaller than 10 mm, were examined by ultrasound (5-13 MHz) prior to stereotactic aspiration macrobiopsy (30 benign lesions, three borderline lesions, and 17 malignant lesions, including ten in situ lesions and seven invasive lesions). Mammography had placed 13 of these cases in BI-RADS 3, 24 in BI-RADS 4, and 13 in BI-RADS 5. The BI-RADS classification was also used for ultrasound assessment.

RESULTS: Six of the 18 microcalcifications that were not seen by ultrasound were malignant (two invasive ductal cancers [IDC] and four ductal carcinomas in situ [DCIS]). Two of the four cases with no sonographically visible tissue mass proved to be malignant (one IDC, one DCIS); these two lesions had been classified BI-RADS 4 and 5 by mammography and were larger than 10 mm. Ultrasound visualized 16 masses classed BI-RADS 3, ten masses classed BI-RADS 4, and two masses classed BI-RADS 5. One of the lesions classified as BI-RADS 3 by mammography was an IDC that was classed BI-RADS3 by ultrasound. Four of the lesions classed BI-RADS 4 by mammography were malignant (three were classified BI-RADS3 by ultrasound while one was classed BI-RADS4). One benign lesion was classified BI-RADS 5 by ultrasound. Four cancers were mammographically classed BI-RADS 5; ultrasound was in agreement in one case but classed three of the cases as BI-RADS 4. In one case, ultrasound gave a diagnosis of benignity (BI-RADS 3 classification).

CONCLUSION: Ultrasound is unsuited for the diagnosis of microcalcifications because it fails to visualize a mass in one-third of cancers and the existence of a mass is correlated with malignancy in one-third of cases. Furthermore, US does not correct the false-negative errors of mammography, and it underestimates the rate of malignancy by ascribing a benign appearance to 50% of cancers, which mammography correctly classifies BI-RADS 4 or 5.}, } @article {pmid17212145, year = {2006}, author = {Sakurai, K and Amano, S and Enomoto, K and Matsuo, S}, title = {[A case of advanced breast cancer with meningeal carcinomas and orbital metastasis successfully treated with multi-disciplinary therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {33}, number = {12}, pages = {1913-1915}, pmid = {17212145}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal/*pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Meningeal Neoplasms/drug therapy/radiotherapy/*secondary ; Middle Aged ; Orbital Neoplasms/drug therapy/radiotherapy/*secondary ; Paclitaxel/therapeutic use ; Quality of Life ; Tegafur/therapeutic use ; Trastuzumab ; }, abstract = {We report a case of advanced breast cancer with meningeal metastasis and orbital metastasis (T4bN3cM1, Stage IV) achieving a significant improvement in QOL by multi-disciplinary therapy. The patient was a 51-year-old woman who had headaches and an ulcerative breast lump with meningeal metastasis and orbital metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 9 cycles of weekly trastuzumab and radiation therapy for meningeal metastasis and orbital metastasis. Although the size of breast tumor, orbital metastasis lesion, and meningeal metastasis lesion exhibited no change, clinical symptoms were improved. One year later, she received paclitaxel so that the sensitivity of HER2/neu dropped. However, the tumor markers relapsed and we then changed paclitaxel to TS-1. Eighteen-months later, she had no neurological symptoms. Multi disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.}, } @article {pmid17210616, year = {2007}, author = {Kim, HJ and Yang, JS and Woo, SS and Kim, SK and Yun, CH and Kim, KK and Han, SH}, title = {Lipoteichoic acid and muramyl dipeptide synergistically induce maturation of human dendritic cells and concurrent expression of proinflammatory cytokines.}, journal = {Journal of leukocyte biology}, volume = {81}, number = {4}, pages = {983-989}, doi = {10.1189/jlb.0906588}, pmid = {17210616}, issn = {0741-5400}, mesh = {Acetylmuramyl-Alanyl-Isoglutamine/*pharmacology ; Cell Differentiation ; Cytokines/*metabolism ; Dendritic Cells/drug effects/metabolism/*physiology ; Drug Synergism ; Endocytosis ; Histocompatibility Antigens Class II/metabolism ; Humans ; Inflammation/*metabolism ; Interleukin-10/immunology/metabolism ; Interleukin-12/metabolism ; Lipopolysaccharides/*pharmacology ; Monocytes/drug effects/metabolism/physiology ; Teichoic Acids/*pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Maturation is an important process by which dendritic cells (DC) develop the potent antigen-presentation capacity necessary for efficient activation of adaptive immunity. Here, we have investigated the ability of lipoteichoic acid (LTA) and muramyl dipeptide (MDP; the minimal structural unit of peptidoglycan with immunostimulating activity) to induce maturation of human immature DC (iDC), derived from peripheral blood CD14-positive cells, and the production of proinflammatory cytokines. Exposure of iDC to staphylococcal LTA (StLTA) at 1 or 10 microg/ml or MDP at 0.1 or 1 microg/ml alone had little effect on the expression of CD80 and CD83, with a minor increase in expression of CD86, all of which are indicative of cell surface markers for maturation. However, there was a synergistic expression of these molecules when iDC were stimulated with StLTA and MDP together. It is interesting that selective induction of MHC Class II expression was observed during the DC maturation, only when costimulated with LTA plus MDP, and Escherichia coli LPS induced dramatic expression of MHC Classes I and II. Endocytosis assay using Dextran-FITC showed that costimulation with StLTA and MDP attenuated the endocytic capacity of the DC, which is a typical phenomenon of DC maturation. Concomitantly, increased expression of DEC-205, but decreased expression of CD206, was observed under the same costimulating condition. Furthermore, ELISA showed that secretions of TNF-alpha and IL-12 p40, but not IL-10, were induced in iDC by the costimulation. These results suggest that StLTA and MDP synergistically induce maturation and activation of human DC.}, } @article {pmid17207563, year = {2007}, author = {Bouaffre, S and Faïta-Ainseba, F}, title = {Hemispheric differences in the time-course of semantic priming processes: evidence from event-related potentials (ERPs).}, journal = {Brain and cognition}, volume = {63}, number = {2}, pages = {123-135}, doi = {10.1016/j.bandc.2006.10.006}, pmid = {17207563}, issn = {0278-2626}, mesh = {Adult ; Analysis of Variance ; Association Learning/physiology ; Attention/physiology ; Cues ; Evoked Potentials/*physiology ; Female ; Functional Laterality/*physiology ; Humans ; Language ; Male ; Photic Stimulation ; Reaction Time/*physiology ; Reference Values ; *Semantics ; Verbal Learning/*physiology ; }, abstract = {To investigate hemispheric differences in the timing of word priming, the modulation of event-related potentials by semantic word relationships was examined in each cerebral hemisphere. Primes and targets, either categorically (silk-wool) or associatively (needle-sewing) related, were presented to the left or right visual field in a go/no-go lexical decision task. The results revealed significant reaction-time and physiological differences in both visual fields only for associatively related word pairs, but an electrophysiological difference also tended to reach significance for categorically related words when presented in the left visual field. ERP waveforms showed a different time-course of associative priming effects according to the field of presentation. In the right visual field/left hemisphere, both N400 and Late Positive Component (LPC/P600) were modulated by semantic relatedness, while only a late effect was present in the left visual field/ right hemisphere.}, } @article {pmid17206481, year = {2007}, author = {Valdes, EK and Boolbol, SK and Cohen, JM and Feldman, SM}, title = {Intra-operative touch preparation cytology; does it have a role in re-excision lumpectomy?.}, journal = {Annals of surgical oncology}, volume = {14}, number = {3}, pages = {1045-1050}, doi = {10.1245/s10434-006-9263-x}, pmid = {17206481}, issn = {1068-9265}, mesh = {Biopsy ; Breast Neoplasms/epidemiology/pathology/*surgery ; Carcinoma in Situ/epidemiology/pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/pathology/surgery ; Cytological Techniques ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Incidence ; Intraoperative Care/methods/*standards ; Mastectomy, Segmental/*standards ; Neoplasm Invasiveness/pathology ; Neoplasm Recurrence, Local/epidemiology/pathology ; Prospective Studies ; Reoperation ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Breast carcinoma is the most frequently diagnosed malignancy in women of North America. The combination of breast conservation surgery and radiotherapy has become a standard of treatment for the majority of breast cancers. It is critical to obtain clear margins to minimize local recurrence. However, avoiding multiple re-excisions for margin clearance helps optimize cosmetic results in patients undergoing breast conservation surgery. Intra-operative touch preparation cytology (IOTPC) may decrease the need for multiple re-excisions and thereby improve cosmesis. The literature suggests that IOTPC can be useful in evaluation of margins. Klimberg et al. evaluated the touch preparation technique prospectively in 428 patients undergoing breast biopsy for undiagnosed breast masses. Margin evaluation was correct in 100% of the lesions and was used to re-excise the margins when touch prep results were positive. They reported a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 100% for the touch prep technique. To the best of our knowledge, there has been no published data on the role of IOTPC for evaluation of margins in re-excision cases. This report describes our experience with IOTPC for margin assessment for re-excision partial mastectomy at Beth Israel Medical Center (BIMC). The purpose of this study is to determine whether IOTPC is reliable for evaluating margins in patients undergoing re-excision for involved or close margins.

METHODS: A prospective study of 30 patients, who have undergone re-excision partial mastectomy for involved or close margins after breast conservation surgery with the use of IOTPC for margin assessment at BIMC was performed. The re-excision lumpectomy specimens were oriented by the surgeon intra-operatively and were submitted fresh to pathology for cytologic assessment. The touch prep method consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present they will stick to the slide, while fat cells will not. A slide was prepared for each re-excision specimen. Air-dried samples were stained immediately using the Diff-Quik method and examined under the microscope by a cytopathologist.

RESULTS: Thirty patients underwent re-excision lumpectomy for involved or close margins with touch preparation cytology for assessment of 68 margins. Twenty-six patients had invasive ductal carcinoma and/or ductal carcinoma in situ, three patients had invasive lobular carcinoma and the remaining one patient had a combination of invasive lobular and ductal carcinoma. There was a correlation between touch prep cytology and final pathology in 56/68 margins, which accounts for 82.4% of the cases.

CONCLUSION: Intra-operative touch preparation cytology for assessment of margins in patients undergoing re-excision lumpectomy for involved or close margins has a sensitivity of 75%, specificity of 82.8%, positive predictive value of 21.4%, and negative predictive value of 98.2%. This high negative predictive value and a single false negative margin are quite significant. Therefore, based on our experience, IOTPC can be a useful tool for intra-operative assessment of margins for patients undergoing re-excision partial mastectomy.}, } @article {pmid17205249, year = {2007}, author = {Munhoz, AM and Filassi, JR and Aldrighi, C and Ricci, MD and Martella, E and de Barros, AC and Gemperli, R and Ferreira, MC}, title = {Bilateral reduction mammaplasty for immediate breast conservation surgery reconstruction and intraoperative radiotherapy: a preliminary report.}, journal = {Aesthetic plastic surgery}, volume = {31}, number = {1}, pages = {94-100}, doi = {10.1007/s00266-006-0200-y}, pmid = {17205249}, issn = {0364-216X}, mesh = {Adult ; Breast Neoplasms/*radiotherapy/*surgery ; Combined Modality Therapy ; Female ; Humans ; *Intraoperative Period ; *Mammaplasty ; *Mastectomy, Segmental ; }, abstract = {BACKGROUND: Breast conservation surgery and postoperative radiotherapy are widely accepted as the treatment of choice for patients with early breast cancer. Despite its oncologic benefits, the radiotherapy may cause unpredictable outcomes in soft tissues, especially in patients undergoing breast reconstruction. Described recently, intraoperative irradiation (IORT) has been indicated for selected patients as an alternative to radiotherapy with fewer adverse local effects. Clinical use of reduction mammaplasty (RM) techniques in oncologic breast surgery has been described previously. However, no previous studies have mentioned its application after breast conservation surgery and IORT.

METHODS: The authors used RM to reconstruct a partial breast tissue defect secondary to breast conservation surgery followed by IORT treatment in a 46-year-old patient with an 11-mm invasive ductal carcinoma between the superior internal quadrants of the right breast.

RESULTS: Satisfactory breast volume and shape were achieved, and no immediate or late complications were observed. After 2 postoperative years, no evidence of fat necrosis, tumor recurrence, or tissue volume loss was observed.

CONCLUSION: The initial data indicate that RM in the setting of breast conservation surgery reconstruction and IORT is feasible. With appropriate patient selection, respecting indications and limitations, RM has its place among the various reconstructive techniques. Additional studies with larger clinical series and longer follow-up periods are necessary to analyze the precise IORT effects in patients submitted to immediate breast conservation surgery reconstruction.}, } @article {pmid17202372, year = {2007}, author = {Bouhlal, H and Chomont, N and Réquena, M and Nasreddine, N and Saidi, H and Legoff, J and Kazatchkine, MD and Bélec, L and Hocini, H}, title = {Opsonization of HIV with complement enhances infection of dendritic cells and viral transfer to CD4 T cells in a CR3 and DC-SIGN-dependent manner.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {178}, number = {2}, pages = {1086-1095}, doi = {10.4049/jimmunol.178.2.1086}, pmid = {17202372}, issn = {0022-1767}, mesh = {CD4-Positive T-Lymphocytes/*metabolism ; Cell Adhesion Molecules/*metabolism ; Cell Differentiation ; Cell Transformation, Viral/*physiology ; Cells, Cultured ; Complement System Proteins/*metabolism ; Dendritic Cells/cytology/*metabolism ; HIV/*physiology ; Humans ; Lectins, C-Type/*metabolism ; Macrophage-1 Antigen/*metabolism ; Monocytes/cytology/metabolism ; Phenotype ; Receptors, CCR5/metabolism ; Receptors, CXCR4/metabolism ; Receptors, Cell Surface/*metabolism ; }, abstract = {In the present study, we demonstrated that opsonization of primary HIV-1 with human complement enhances infection of immature monocyte-derived dendritic cells (iDC) and transmission in trans of HIV to autologous CD4(+) T lymphocytes. Infection of iDC by opsonized primary R5- and X4-tropic HIV was increased 3- to 5-fold as compared with infection by the corresponding unopsonized HIV. Enhancement of infection was dependent on CR3 as demonstrated by inhibition induced by blocking Abs. The interaction of HIV with CCR5 and CXCR4 on iDC was affected by opsonization. Indeed, stromal-derived factor-1 was more efficient in inhibiting infection of iDC with opsonized R5-tropic HIV-1(BaL) (45%) than with heat-inactivated complement opsonized virus and similarly RANTES inhibited more efficiently infection of iDC with opsonized X4-tropic HIV-1(NDK) (42%) than with heat-inactivated complement opsonized virus. We also showed that attachment of complement-opsonized virus to DC-specific ICAM-grabbing nonintegrin (DC-SIGN) molecule on iDC and HeLa DC-SIGN(+) CR3(-) cells was 46% and 50% higher compared with heat-inactivated complement opsonized virus, respectively. Hence, Abs to DC-SIGN suppressed up to 80% and 60% the binding of opsonized virus to HeLa cells and iDC, respectively. Furthermore, Abs to DC-SIGN inhibited up to 70% of the infection of iDC and up to 65% of infection in trans of autologous lymphocytes with opsonized virus. These results further demonstrated the role of DC-SIGN in complement opsonized virus uptake and infection. Thus, the virus uses complement to its advantage to facilitate early steps leading to infection following mucosal transmission of HIV.}, } @article {pmid17199742, year = {2007}, author = {Tanahashi, C and Yabuki, S and Akamine, N and Yatabe, Y and Ichihara, S}, title = {Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman.}, journal = {Pathology international}, volume = {57}, number = {1}, pages = {43-46}, doi = {10.1111/j.1440-1827.2007.02055.x}, pmid = {17199742}, issn = {1320-5463}, mesh = {Aged, 80 and over ; Antigens, CD7/metabolism ; Breast Neoplasms/*diagnosis/metabolism/*pathology ; Carcinoma, Acinar Cell/*diagnosis/metabolism/*pathology ; Female ; Humans ; Japan ; Keratin-20/metabolism ; }, abstract = {Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case of this rare variant of breast carcinoma was reported in 1996, only 10 cases have been reported in the English-language literature. Reported herein is the first case of primary acinic cell carcinoma of the breast in a Japanese woman. To the naked eye, the tumor appeared well circumscribed and the cut surface was grayish-pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a monotonous proliferation of cells with a finely granular cytoplasm, resembling acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm. In spite of extensive sampling, no common histological patterns of breast carcinoma such as in situ and invasive ductal carcinoma were recognized in the present case, indicating that the present case was pure acinic cell carcinoma. In addition, the immunohistochemical profile of this tumor was identical to that of the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were positive. The patient has been well for 22 months since the wide local excision of the tumor and no signs of salivary neoplasm are evident to date.}, } @article {pmid17198087, year = {2007}, author = {Zhang, R and Bharadwaj, U and Li, M and Chen, C and Yao, Q}, title = {Effects of pentoxifylline on differentiation, maturation, and function of human CD14+ monocyte-derived dendritic cells.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {30}, number = {1}, pages = {89-95}, doi = {10.1097/01.cji.0000211323.53396.38}, pmid = {17198087}, issn = {1524-9557}, support = {AT003094/AT/NCCIH NIH HHS/United States ; DE15543/DE/NIDCR NIH HHS/United States ; EB-002436/EB/NIBIB NIH HHS/United States ; HL083471/HL/NHLBI NIH HHS/United States ; HL65916/HL/NHLBI NIH HHS/United States ; HL72716/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Differentiation/drug effects/immunology ; Dendritic Cells/*drug effects/*immunology ; Humans ; Interferon-gamma/biosynthesis/immunology ; Lipopolysaccharide Receptors/*immunology ; Lymphocyte Activation/drug effects/immunology ; Monocytes/*drug effects/immunology ; Pentoxifylline/*pharmacology ; T-Lymphocytes/drug effects/immunology ; Tumor Necrosis Factor-alpha/biosynthesis/immunology ; }, abstract = {Pentoxifylline (PTX) is a nonspecific phosphodiesterase inhibitor which has potent immunoregulatory and antiinflammatory effects. Although its immunomodulation property has been recognized, it is not clear whether PTX could affect dendritic cells (DCs), the most efficient antigen-presenting cells. The purpose of this study was to determine whether PTX could suppress DC differentiation, maturation, and its associated functions. Immature DCs (iDCs) were generated from human peripheral blood mononuclear cell CD14+ monocytes cultured with granulocyte macrophage colony stimulating factor and interleukin-4 for 5 days. PTX concentration-dependently suppressed the expression of iDC differentiation markers including CD54, CD80, CD86, and human leukocyte antigen-DR. In addition, PTX also inhibited DC maturation marker CD83 expression after stimulating DCs with lipopolysaccharide. Furthermore, PTX inhibited the antigen-uptake ability of DCs when tested by fluorescein isothiocyanate-dextran endocytosis assay. PTX significantly reduced the production of TNF-alpha and IFN-gamma in mature DCs (mDCs). Consequently, PTX-treated mDCs showed a reduced activity of mDC-induced T-cell allostimulation and proliferation by mixed-lymphocyte reaction (MLR) assay. Therefore, PTX significantly inhibits CD14+ monocyte-derived DC differentiation, maturation, antigen-uptake ability of iDCs, and antigen-presentation ability of mDCs possibly due to the suppression of TNF-alpha and IFN-gamma production. These results suggested that inhibitory effects of PTX on DCs may contribute its antiinflammatory and immunoregulatory functions.}, } @article {pmid17196511, year = {2007}, author = {Katz, A and Saad, ED and Porter, P and Pusztai, L}, title = {Primary systemic chemotherapy of invasive lobular carcinoma of the breast.}, journal = {The Lancet. Oncology}, volume = {8}, number = {1}, pages = {55-62}, doi = {10.1016/S1470-2045(06)71011-7}, pmid = {17196511}, issn = {1470-2045}, mesh = {Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology ; Carcinoma, Lobular/*drug therapy/pathology ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Female ; Humans ; Incidence ; Neoplasm Invasiveness/*pathology ; }, abstract = {Invasive lobular carcinoma is the second most frequent histological type of breast cancer and its incidence is increasing. It has unique clinical, biological, and molecular features. Invasive lobular carcinoma is almost invariably positive for the oestrogen receptor and, when compared with invasive ductal carcinoma, it is typically of a lower grade. Even though invasive lobular carcinoma represents a distinct clinical entity, the same criteria used for invasive ductal carcinoma are currently applied to establish the need for primary or adjuvant systemic chemotherapy. We reviewed randomised trials of neoadjuvant and adjuvant chemotherapy and noted that insufficient evidence is available to support or withhold use of chemotherapy in patients with invasive lobular carcinoma. Thus, the benefit from systemic chemotherapy for individuals with this form of breast disease is unclear. Invasive lobular carcinoma deserves to be investigated separately in prospective clinical trials to define the best treatment and prevention strategies.}, } @article {pmid17196363, year = {2007}, author = {Snoj, M and Arnez, ZM and Sadikov, A and Suvorov, N}, title = {Breast reconstruction following mastectomy for invasive breast cancer by free flaps from the abdomen is oncologically safe.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {33}, number = {5}, pages = {541-545}, doi = {10.1016/j.ejso.2006.11.024}, pmid = {17196363}, issn = {0748-7983}, mesh = {*Abdominal Muscles ; Adult ; Aged ; Breast Neoplasms/*surgery ; Female ; Follow-Up Studies ; Humans ; Mammaplasty/*methods ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; *Surgical Flaps ; Treatment Outcome ; }, abstract = {AIMS: To report the long-term results of oncological safety of breast reconstruction by autologous tissue following mastectomy for invasive breast cancer.

METHODS: One-hundred-fifty-six consecutive patients with invasive breast cancer treated with mastectomy and reconstruction by autologous tissue were reviewed throughout (from 1987 to 2003 with median follow up time of 66 months).

RESULTS: Median patient age was 45.9 years (range 26-68). The 157 observed tumors had mean diameter of 25+/-19 mm, 70 of them were poorly differentiated, and 137 were invasive ductal carcinoma. Multifocal disease was present in 44 patients. Breast reconstruction was carried out only by autologous tissue (free flaps were used in 95% and free TRAM flap transfer was the most common reconstructive procedure). There was only one local recurrence as first site of recurrence, thus yielding a local recurrence rate of 0.6%.

CONCLUSIONS: Breast reconstruction by autologous tissue following mastectomy for invasive breast cancer is an oncologically safe procedure.}, } @article {pmid20306655, year = {2007}, author = {Zeiwar, MM and Zaki, SM and Mohammad, LA and Zidan, AA and El Nagar, MR}, title = {HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in breast cancer patients.}, journal = {The Egyptian journal of immunology}, volume = {14}, number = {2}, pages = {29-41}, pmid = {20306655}, issn = {1110-4902}, mesh = {Adult ; Aged ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/genetics/*pathology ; Carcinoembryonic Antigen/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; *Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Middle Aged ; Mucin-1/*blood ; Nucleosomes/*metabolism ; Polymerase Chain Reaction ; Predictive Value of Tests ; Prognosis ; ROC Curve ; }, abstract = {Breast cancer is the most frequently diagnosed cancer in women in the world, for which tumor markers are needed for early detection, clinical prognistication and monitoring. The study was designed to assess the usefulness of HER-2 gene amplification, serum nucleosomes, CEA and CA15.3 tumor markers in the diagnosis of invasive ductal carcinoma and analyze whether their levels correlate with the clinicopathological features. The study was carried out on fifty patients with invasive ductal carcinoma and 25 age matched women with benign breast diseases (BBD). Cancer patients were categorised into three subgroups according to absence (-) or presence (+) of axillary lymph nodes (N) or presence of distant metastasis (M+) into: subgroup I (N-) included 15 patients, subgroup II (N+) included 20 patients and subgroup III (M+) included 15 patients. All individuals were subjected to CBC, fasting blood sugar, liver & kidney function tests, CEA and CA15.3 by electrochemiluminescence, serum nucleosomes by cell death detection ELISA and amplification of HER-2 gene by differential PCR. The HER-2 gene PCR results were + ve in 28% of cancer patients; 20% of subgroup I, 25% of subgroup II and 40% of subgroup III, but in none of the BBD patients. HER-2 gene amplification results showed significant positive correlation with tumor grade. Serum nucleosomes showed significant increase in cancer patients as compared to that of BBD group, significant negative correlation with HER-2 gene amplification and significant positive correlation with CA15.3. Serum nucleosomes was the most sensitive marker (76% versus 32% and 50% for CEA & CA15.3 respectively) but the least specific (72% versus 92% and 96% for CEA & CA15.3 respectively). Elevated CEA and CA15.3 levels were detected in 13.3% and 33.3% respectively in node negative patients, these percentage increased in node positive patients to 20% and 40% and in metastatic patients to 66.7% and 80% respectively. In conclusion, serum nucleosomes is more sensitive but less specific marker than CEA and CA15.3 for diagnosis of early-stage breast cancer. HER-2 gene amplification is a potential prognostic marker for advanced stage breast cancer.}, } @article {pmid17189983, year = {2006}, author = {Sahin, FI and Yilmaz, Z and Yagmurdur, MC and Atac, FB and Ozdemir, BH and Karakayali, H and Demirhan, B and Haberal, M}, title = {Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients.}, journal = {Pathology oncology research : POR}, volume = {12}, number = {4}, pages = {211-215}, pmid = {17189983}, issn = {1219-4956}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/secondary ; Carcinoma, Lobular/genetics/secondary ; Female ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Prognosis ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/metabolism ; }, abstract = {The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.}, } @article {pmid17184588, year = {2007}, author = {Zhang, CL and Zou, XL and Peng, JB and Xiang, M}, title = {Immune tolerance induced by adoptive transfer of dendritic cells in an insulin-dependent diabetes mellitus murine model.}, journal = {Acta pharmacologica Sinica}, volume = {28}, number = {1}, pages = {98-104}, doi = {10.1111/j.1745-7254.2007.00467.x}, pmid = {17184588}, issn = {1671-4083}, mesh = {Adoptive Transfer/*methods ; Animals ; CD4 Antigens/immunology ; Cell Proliferation ; Cytokines/blood ; Dendritic Cells/*immunology/transplantation ; Diabetes Mellitus, Type 1/chemically induced/*immunology/therapy ; Flow Cytometry ; *Immune Tolerance ; Interleukin-2 Receptor alpha Subunit/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Streptozocin ; T-Lymphocytes/immunology/pathology ; }, abstract = {AIM: To investigate the effect and underlying mechanisms of immune-tolerance induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC) in insulin-dependent diabetes mellitus (IDDM) mice.

METHODS: The IDDM model was established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC subpopulations were generated from the BM cells with granulocyte-macrophage colony-stimulating factor with or without interleukin-4. The purity and the T cell stimulatory capability of DC were identified. These cells were used to modulate autoimmune response in pre-diabetic mice. Blood glucose was examined weekly; pancreas tissues were taken for histopathological analysis, and CD4(+) T cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio of CD4(+)CD25(+) T cells by fluorescence-activated cell sorting (FACS). The cytokine secretion was determined by ELISA analysis.

RESULTS: Two DC subsets were generated from BM, which have phenotypes of mature DC (mDC) and immature DC (iDC), respectively. The level of blood glucose decreased significantly by transferring iDC (P< 0.01) rather than mDC. Less lymphocyte infiltration was observed in the islets, and pancreatic structure was intact. In vitro, proliferation of lymphocytes decreased and the proportion of CD4(+)CD25(+) T cells increased remarkably, compared with the mDC-treated groups (P< 0.05), which were associated with increased level of the Th2 cytokine and reduced level of the Th1 cytokine after iDC transfer.

CONCLUSION: Our data showed that iDC transfer was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance to IDDM may be associated with promoting the production of CD4(+)CD25(+) T cells and inducing regulatory Th2 responses in vivo.}, } @article {pmid17178859, year = {2006}, author = {Yang, C and Trent, S and Ionescu-Tiba, V and Lan, L and Shioda, T and Sgroi, D and Schmidt, EV}, title = {Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression.}, journal = {Cancer research}, volume = {66}, number = {24}, pages = {11649-11658}, doi = {10.1158/0008-5472.CAN-06-1645}, pmid = {17178859}, issn = {0008-5472}, support = {P50 CA89393/CA/NCI NIH HHS/United States ; R01 CA69069/CA/NCI NIH HHS/United States ; }, mesh = {3T3 Cells ; Animals ; Breast/cytology/pathology/physiology/physiopathology ; Breast Neoplasms/*genetics/*pathology ; Cyclin D1/*genetics ; Disease Progression ; Estrogens/*physiology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hyperplasia ; Mice ; Mice, Transgenic ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Reference Values ; }, abstract = {Tumors can become lethal when they progress from preinvasive lesions to invasive carcinomas. Here, we identify candidate tumor progression genes using gene array analysis of preinvasive and invasive tumors from mice, which were then evaluated in human cancers. Immediate early response protein IEX-1, small stress protein 1 (HSPB8), and tumor necrosis factor-associated factor-interacting protein mRNAs displayed higher expression levels in invasive lesions than in preinvasive lesions using samples obtained by laser capture microdissection (LCM) from transgenic erbB2, ras, and cyclin D1 mice. LCM-isolated tissues from patient-matched normal, ductal carcinoma in situ, and invasive ductal carcinoma revealed similar increased expression in invasive human cancers compared with preinvasive and normal samples. These genes induced anchorage independence, increased cell proliferation, and protected against apoptosis, singly or in collaboration with erbB2. Surprisingly, they were all up-regulated by 17beta-estradiol and cyclin D1, and cyclin D1 overexpression increased p300/CBP binding to their promoters, supporting the model that cyclin D1-estrogen receptor (ER) coactivator interactions may be important to its role in ER-positive breast cancer. Additionally, an irreversible dual kinase inhibitor of ErbB signaling inhibited expression of the same genes. The up-regulation of genes contributing to increased invasiveness of ER-positive cancers offers a novel explanation for the contribution of cyclin D1 to a worse prognosis in ER-positive cancers. As targets of estrogen, cyclin D1, and erbB2 signaling, these candidates offer insights into the nature of the second events involved in breast cancer progression, regulatory events contributing to invasion, and potential targets of combined inhibition of hormone and growth factor signaling pathways.}, } @article {pmid17172497, year = {2007}, author = {Irie, J and Manucha, V and Ioffe, OB and Silverberg, SG}, title = {Artefact as the pathologist's friend: peritumoral retraction in in situ and infiltrating duct carcinoma of the breast.}, journal = {International journal of surgical pathology}, volume = {15}, number = {1}, pages = {53-59}, doi = {10.1177/1066896906295690}, pmid = {17172497}, issn = {1066-8969}, mesh = {*Artifacts ; Biomarkers, Tumor ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; *Tissue Fixation ; }, abstract = {Peritumoral retraction artefact appears in tissue sections as an empty space partially or completely encircling a nest of tumor cells, usually in conformity with the rounded or angular outline of that particular nest. The present study was designed to test this finding in a large series of cases and to quantify the appearance of peritumoral retraction artefact in, in situ and infiltrating duct carcinoma of the breast. We examined 199 cases of infiltrating duct carcinoma (IDC) and 188 cases of ductal carcinoma in situ (DCIS). Of the total of 387 cases, 111 were core needle biopsies, whereas the others were larger resections. In each specimen, retraction was evaluated on hematoxylin and eosin-stained slides as negative, 1+ (1% to 25% of tumor showing retraction), 2+ (26% to 50%), 3+ (51% to 75%), or 4+ (76% to 100%). Overall, peritumoral retraction was noted in 168 of 199 cases (84.4%) of IDC, versus 30 of 188 cases (16%) of DCIS (P < 0.0001). Peritumoral retraction scored as 2+ or greater (26% to 50%) was seen in only 1 of 188 DCIS specimens, compared with 77 of 199 IDC. Thus, peritumoral retraction artefact appears to be a significant finding seen during the evaluation of hematoxylin and eosin specimens for the diagnosis of carcinoma. We discuss the possibility that this phenomenon might represent true prelymphatic space involvement rather than a fixation artefact.}, } @article {pmid17171496, year = {2007}, author = {Doi, R and Kami, K and Ito, D and Fujimoto, K and Kawaguchi, Y and Wada, M and Kogire, M and Hosotani, R and Imamura, M and Uemoto, S}, title = {Prognostic implication of para-aortic lymph node metastasis in resectable pancreatic cancer.}, journal = {World journal of surgery}, volume = {31}, number = {1}, pages = {147-154}, pmid = {17171496}, issn = {0364-2313}, mesh = {Aged ; Aorta ; Carcinoma, Pancreatic Ductal/*mortality/*pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic Vessels/pathology ; Male ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*mortality/*pathology/surgery ; Pancreaticoduodenectomy ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; }, abstract = {BACKGROUND: The survival curve of patients who undergo surgical resection of pancreatic cancer displays a steep decline within 1 year and a relatively slow decline thereafter. The patients with a short survival time may have identifiable clinicopathologic factors that lead to rapid relapse.

STUDY DESIGN: We analyzed clinicopathologic factors in 133 patients who underwent margin-negative pancreatoduodenectomy with extended radical lymphadenectomy for invasive ductal carcinoma of the pancreas to detect factors that could be responsible for the short survival.

RESULTS: Tumor size, invasion of the anterior pancreatic capsule, retroperitoneal invasion, portal venous invasion, major arterial invasion, and metastasis to the para-aortic lymph nodes were variables associated with survival time in univariate analysis. Metastasis to the para-aortic lymph nodes was the single independent factor with a significant association with mortality in multivariate analysis. Some 84% of the patients who had positive para-aortic lymph nodes died within 1 year, versus 46% of the patients with negative nodes.

CONCLUSIONS: Although tumors that involve the para-aortic lymph nodes may technically be resectable, the expected postoperative survival time for most patients is less than 1 year. If para-aortic nodal metastasis is detected, alternative treatment strategies should be considered.}, } @article {pmid17169608, year = {2007}, author = {Gullu, H and Erdogan, D and Caliskan, M and Tok, D and Kulaksizoglu, S and Yildirir, A and Muderrisoglu, H}, title = {Elevated serum uric acid levels impair coronary microvascular function in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of heart failure}, volume = {9}, number = {5}, pages = {466-468}, doi = {10.1016/j.ejheart.2006.10.019}, pmid = {17169608}, issn = {1388-9842}, mesh = {Adult ; Aged ; Biomarkers/blood ; Blood Flow Velocity ; Cardiomyopathy, Dilated/*blood/etiology/*physiopathology ; *Coronary Circulation ; Endothelium, Vascular/metabolism/physiopathology ; Female ; Humans ; Hyperuricemia/blood/complications/physiopathology ; Logistic Models ; Male ; *Microcirculation ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Stroke Volume ; Uric Acid/*blood ; }, abstract = {In patients with idiopathic dilated cardiomyopathy (IDC), attenuated coronary flow reserve (CFR) and elevated serum uric acid levels have been reported. In this study, we investigated whether increased uric acid levels correlate with the degree of coronary microvascular dysfunction. Serum uric acid levels were measured in 29 patients with IDC (mean age: 57.0+/-10.8 years, 10 female), and each patient also underwent transthoracic echocardiographic examination including CFR measurement. The study population was divided into two groups according to the median CFR value (lower CFR group and higher CFR group). Uric acid levels were significantly higher in the lower CFR group than in the higher CFR group (7.59+/-2.56 vs 4.80+/-0.80 mg/dL, P=0.000). CFR correlated significantly and inversely to serum uric acid (r=-0.570, P=0.001). Logistic regression analysis revealed that uric acid level was the only independent predictor of CFR (B=-1080, P=0.015). We found a possibly clinically important negative association between serum uric acid levels and CFR in patients with IDC.}, } @article {pmid17167977, year = {2006}, author = {Bolat, F and Kayaselcuk, F and Nursal, TZ and Yagmurdur, MC and Bal, N and Demirhan, B}, title = {Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {25}, number = {3}, pages = {365-372}, pmid = {17167977}, issn = {0392-9078}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/metabolism/pathology ; Carcinoma, Lobular/blood supply/metabolism/pathology ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Macrophages/*pathology ; Microcirculation ; Middle Aged ; Mitosis ; Neoplasm Invasiveness/pathology ; Neovascularization, Pathologic/metabolism/*pathology ; Prognosis ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.}, } @article {pmid17165439, year = {2006}, author = {Cagayan, MS and Gacoba, MC}, title = {Chemotherapy regimens used in the treatment of gestational trophoblastic neoplasia at Philippine General Hospital: treatment outcomes and toxicity.}, journal = {The Journal of reproductive medicine}, volume = {51}, number = {11}, pages = {907-918}, pmid = {17165439}, issn = {0024-7758}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Developing Countries ; Female ; Gestational Trophoblastic Disease/*drug therapy/pathology/surgery ; Humans ; Middle Aged ; Neoplasm Metastasis ; Philippines ; Pregnancy ; Retrospective Studies ; }, abstract = {OBJECTIVE: To describe different chemotherapy regimens used in the treatment of gestational trophoblastic neoplasia (GTN).

METHODS: A retrospective study of GTN cases from January 1999 to December It is important 2004 at Philippine General

CONCLUSION: In the Philippine General Hospital, methotrexate is first-line patients single-agent chemotherapy ntitfy those who are rh risk to be able methotrexate, ACT, cyclo-Hospital was done. Patients correctly and idc with nonmetastatic and met- truly low risk vs. phosphamide and vincristine regimen are the first line for high-risk metastatic GTN. Present regimens are effective but predispose patients to a variety of toxicities. Patients' acceptance and tolerance of adverse effects and ability to secure drug resources are factors contributing to the success of the treatment. astatic low-risk disease were managed by single-agent chemotherapy. Those with high-risk disease were given multiple-agent chemotherapy.

RESULTS: Forty-five percent of patients (87/193) manifested adverse reactions to chemotherapy. Adverse effects include anemia in 51.7% (45/87), leukopenia in 16% (14/87), neutropenia in 72.4% (63/87) and elevated liver enzymes in 21.8% (19/87). Symptoms included vomiting in 9.1% (8/87) of cases, diarrhea in 6.8% (6/87), stomatitis in 24.14% (21/87) and febrile neutropenia in 19.5% (17/87). There was a significant difference between the 3 groups of regimens in terms of anemia (p = 0.002), leukopenia (p = 0.011), neutropenia (p < 0.001) and stomatitis (p < 0.001). Patients treated with etoposide, methotrexate, actinomycin (ACT), cyclophosphamide and vincristine and with etoposide, methotrexate, ACT, taxanes and cisplatin experienced most of the toxicity.

CONCLUSION: In the Philippine General Hospital, methotrexate is first-line single-agent chemotherapy for low-risk GTN. Etoposide, methotrexate, ACT, cyclophosphamide and vincristine regimen are the first line for high-risk metastatic GTN. Present regimens are effective but predispose patients to a variety of toxicities. Patients' acceptance and tolerance of adverse effects and ability to secure drug resources are factors contributing to the success of the treatment.}, } @article {pmid17165026, year = {2007}, author = {Mrhalova, M and Kodet, R}, title = {A modified approach for I-FISH evaluation of ERBB2 (HER-2) gene copy numbers in breast carcinomas: comparison with HER-2/CEP17 ratio system.}, journal = {Journal of cancer research and clinical oncology}, volume = {133}, number = {5}, pages = {321-329}, pmid = {17165026}, issn = {0171-5216}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; *Gene Dosage ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Receptor, ErbB-2/*metabolism ; }, abstract = {PURPOSE: The evaluation of ERBB2 gene copy numbers and ERBB-2 protein expression in invasive duct carcinomas of the mammary gland (IDC) has been introduced as a part of a regular investigation protocol. Amplification of the ERBB2 gene detected by fluorescence in situ hybridization on interphasic nuclei (I-FISH) is used as a criterion for Herceptin administration. To improve characterization of cases with a borderline ERBB2 gene amplification, we applied a modified evaluation of the ERBB2 gene copy numbers. The results were compared with a commonly used HER-2/CEP17 ratio calculation.

METHODS: We investigated 175 patients with primary IDCs in histological sections from paraffin embedded tissue with PathVysion HER-2 DNA Probe Kit (Vysis). Tumor cells of each case were sorted according to the number of ERBB2 signals into groups of tumor cells without amplification, with moderate amplification (< or =10 signals) and with strong amplification (>10 signals). If >10% of tumor cells had moderate or strong amplification of the ERBB2 gene, the case was reported as "moderately" or "strongly" amplified.

RESULTS: The groups of patients classified by the proposed system as "without" and as with "strong" amplification had the HER-2/CEP17 ratio <1.91 (median 1.22, n = 33) and >2.3 (median 6.85, n = 115), respectively. Thus, the findings using the two systems of evaluation yielded similar results for these groups of patients. In cases, classified as with "moderate" amplification, the HER-2/CEP17 ratio varied from 1.3 to 4.77 (median 2.11, n = 27). Twelve of these 27 patients were according to the HER-2/CEP17 ratio system "not amplified" (1.3-1.93, median 1.72). Median percentage of the tumor cells with amplification of the ERBB2 gene was 14.5% in this subgroup. Of these 12 cases, 10 were ERBB-2 protein positive, and would be candidates for Herceptin therapy.

CONCLUSION: The criteria for evaluation of the ERBB2 gene copy number proposed for this study separate gray zone cases with a borderline HER-2/CEP17 finding. The proposed system is easy to apply and characterizes a heterogeneity of the ERBB2 gene copy number in IDC tumor cell population more precisely than the currently used HER-2/CEP17 ratio system.}, } @article {pmid17163418, year = {2007}, author = {Wolf, I and Bose, S and Williamson, EA and Miller, CW and Karlan, BY and Koeffler, HP}, title = {FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer.}, journal = {International journal of cancer}, volume = {120}, number = {5}, pages = {1013-1022}, doi = {10.1002/ijc.22389}, pmid = {17163418}, issn = {0020-7136}, mesh = {Breast/chemistry/metabolism/pathology ; Breast Neoplasms/chemistry/genetics/*pathology ; Carcinoma, Ductal/chemistry/genetics/*pathology ; Estrogen Receptor alpha/genetics ; Gene Expression Regulation, Neoplastic ; Hepatocyte Nuclear Factor 3-alpha/*analysis/genetics/*physiology ; Humans ; Prognosis ; Proliferating Cell Nuclear Antigen/genetics ; RNA, Messenger/analysis/metabolism ; RNA, Small Interfering/pharmacology ; Tissue Array Analysis ; Transcriptional Activation ; Tumor Cells, Cultured ; }, abstract = {The transcription factor Forkhead-box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)-positive MCF-7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER-negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer.}, } @article {pmid17163404, year = {2007}, author = {Jin, JS and Cheng, TF and Tsai, WC and Sheu, LF and Chiang, H and Yu, CP}, title = {Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters.}, journal = {Histology and histopathology}, volume = {22}, number = {3}, pages = {305-309}, doi = {10.14670/HH-22.305}, pmid = {17163404}, issn = {1699-5848}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*enzymology/ethnology/pathology ; Carcinoma, Ductal, Breast/*enzymology/ethnology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/ethnology/pathology ; China/ethnology ; Female ; Fibroadenoma/*enzymology/ethnology/pathology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Staging ; Serine Endopeptidases/*metabolism ; Taiwan/epidemiology ; Tissue Array Analysis ; }, abstract = {Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178+/-12 for fibroadenoma; 275+/-11 for DCIS; 299+/-10 for grade I IDC; 251+/-10 for grade II IDC; and 314+/-11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors.}, } @article {pmid17159656, year = {2007}, author = {Shire, NJ and Rouster, SD and Stanford, SD and Blackard, JT and Martin, CM and Fichtenbaum, CJ and Sherman, KE}, title = {The prevalence and significance of occult hepatitis B virus in a prospective cohort of HIV-infected patients.}, journal = {Journal of acquired immune deficiency syndromes (1999)}, volume = {44}, number = {3}, pages = {309-314}, doi = {10.1097/QAI.0b013e31802e29a9}, pmid = {17159656}, issn = {1525-4135}, support = {AI 25897/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; DNA, Viral/blood/genetics ; Female ; HIV Infections/*complications ; Hepatitis B/*complications/*epidemiology/virology ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/analysis ; Hepatitis B virus/isolation & purification ; Humans ; Male ; Multivariate Analysis ; Ohio/epidemiology ; Polymerase Chain Reaction ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: Occult hepatitis B virus (HBV) is defined as low-level HBV DNA without hepatitis B surface antigen (HBsAg). Prevalence estimates vary widely. We determined the prevalence of occult HBV at the University of Cincinnati Infectious Diseases Center (IDC).

METHODS: Patients in the IDC HIV database (n = 3867) were randomly selected using a 25% sampling fraction. Samples were pooled for HBV nucleic acid extraction. Pools were tested for HBV DNA by a real-time polymerase chain reaction (PCR) assay to co-amplify core/surface protein regions. The PCR assay was run on all individual samples from each DNA pool. DNA samples were tested for HBV serologic markers.

RESULTS: A total of 909 patients without known HBV were selected. The mean CD4 count was 384 cells/mm. Forty-three patients were HBV DNA. Twelve of 43 were DNA/HBsAg (95% confidence interval for database: 0.58% to 1.90%). Five of 12 were negative for all serologic markers. Alanine aminotransferase, aspartate aminotransferase, and HBV DNA titers were elevated in HBsAg patients versus occult patients and versus HIV-monoinfected patients. No other significant differences were detected. No occult HBV patient was on treatment with anti-HBV activity.

CONCLUSIONS: Forty-three percent of those with HBV were not previously identified as HBV, indicating the need for ongoing screening in high-risk populations. Occult HBV may occur in persons with all negative serologic markers, representing a challenge for identification.}, } @article {pmid17156488, year = {2006}, author = {Basu, GD and Liang, WS and Stephan, DA and Wegener, LT and Conley, CR and Pockaj, BA and Mukherjee, P}, title = {A novel role for cyclooxygenase-2 in regulating vascular channel formation by human breast cancer cells.}, journal = {Breast cancer research : BCR}, volume = {8}, number = {6}, pages = {R69}, pmid = {17156488}, issn = {1465-542X}, mesh = {Animals ; Blood Vessels/*drug effects/physiopathology ; Breast Neoplasms/*metabolism ; Celecoxib ; Cell Line, Tumor ; Cyclooxygenase 2/*biosynthesis ; Cyclooxygenase 2 Inhibitors/pharmacology ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Neovascularization, Pathologic/genetics/*metabolism/physiopathology ; Pyrazoles/pharmacology ; Sulfonamides/pharmacology ; }, abstract = {INTRODUCTION: Cyclo-oxygenase (COX)-2 expression correlates directly with highly aggressive and metastatic breast cancer, but the mechanism underlying this correlation remains obscure. We hypothesized that invasive human breast cancer cells that over-express COX-2 have the unique ability to differentiate into extracellular-matrix-rich vascular channels, also known as vasculogenic mimicry. Vascular channels have been associated with angiogenesis without involvement of endothelial cells, and may serve as another mechanism by which tumor cells obtain nutrients to survive, especially in less vascularized regions of the tumor.

METHODS: To determine whether COX-2 regulates vascular channel formation, we assessed whether treatment with celecoxib (a selective COX-2 inhibitor) or silencing COX-2 synthesis by siRNA inhibits vascular channel formation by breast cancer cell lines. Cell lines were selected based on their invasive potential and COX-2 expression. Additionally, gene expression analysis was performed to identify candidate genes involved in COX-2-induced vascular channel formation. Finally, vascular channels were analyzed in surgically resected human breast cancer specimens that expressed varying levels of COX-2.

RESULTS: We found that invasive human breast cancer cells that over-express COX-2 develop vascular channels when plated on three-dimensional matigel cultures, whereas non-invasive cell lines that express low levels of COX-2 did not develop such channels. Similarly, we identified vascular channels in high-grade invasive ductal carcinoma of the breast over-expressing COX-2, but not in low-grade breast tumors. Vascular channel formation was significantly suppressed when cells were treated with celecoxib or COX-2 siRNA. Inhibition of channel formation was abrogated by addition of exogenous prostaglandin E2. In vitro results were corroborated in vivo in tumor-bearing mice treated with celecoxib. Using gene expression profiling, we identified several genes in the angiogenic and survival pathways that are engaged in vascular channel formation.

CONCLUSION: Antivascular therapies targeting tumor cell vasculogenic mimicry may be an effective approach to the treatment of patients with highly metastatic breast cancer.}, } @article {pmid17148928, year = {2006}, author = {Miyagawa, M and Kanemasa, H and Nitan, T and Matsumoto, M and Tokita, K and Kajita, Y and Yanagisawa, A and Nakamura, Y and Sonoyama, T and Yamagishi, H and Mitsufuji, S and Okanoue, T}, title = {[A case of minimal invasive carcinoma from intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {103}, number = {12}, pages = {1384-1390}, pmid = {17148928}, issn = {0446-6586}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/*diagnosis/pathology ; Carcinoma, Papillary/*diagnosis/pathology ; Cholangiopancreatography, Endoscopic Retrograde ; Cystadenocarcinoma, Mucinous/*diagnosis/pathology ; Endosonography ; Humans ; Male ; *Neoplasms, Multiple Primary ; Pancreatic Neoplasms/*diagnosis/pathology ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, abstract = {A 69-year-old man was referred to our hospital for epigastralgia. He was found to have elevation of serum amylase and CA19-9. Ultrasonography, abdominal CT, MRCP, ERCP and EUS showed the cystic lesion and a possibility of an other tumor. There was a stenosis of the main pancreatic duct (MPD) at the pancreas head and dilatation of the MPD from the body to the tail. Intraductal papillary mucinous neoplasm (IPMN) of the branch pancreatic duct was diagnosed, and there was a likelihood of ductal carcinoma of the pancreas. We therefore performed pancreatoduodenectomy. Pathological finding showed invasive carcinoma from an intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas.}, } @article {pmid17146166, year = {2006}, author = {Tsutani, Y and Ohsumi, S and Aogi, K and Taira, N and Kataoka, M and Hamamoto, Y and Nishimura, R and Takashima, S}, title = {A case of metastatic breast cancer with HER2 gene amplification that responded completely to single agent trastuzumab.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {4}, pages = {374-377}, doi = {10.2325/jbcs.13.374}, pmid = {17146166}, issn = {1340-6868}, mesh = {Aged, 80 and over ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/*drug therapy/genetics/pathology ; Carcinoma, Ductal, Breast/*drug therapy/genetics/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; Lymphatic Metastasis ; Trastuzumab ; }, abstract = {An 80-year-old woman visited our hospital with a massive ulcerated tumor in the upper lateral quadrant of the right breast. Her performance status was 2. Histopathologically, a mass consisting of a huge primary tumor and metastatic axillary lymph nodes was seen and invasive ductal carcinoma was diagnosed. Both estrogen and progesterone receptors were negative. Herceptest (DakoCytomation, Glostrup, Denmark) showed 2 + staining and HER2 amplification was detected by fluorescent in situ hybridization. CT revealed multiple lung metastases. Her old age and performance status of 2 made aggressive chemotherapy difficult. After receiving 5'-DFUR 600 mg/day as the first line treatment for two months, the tumors progressed. As second-line treatment, single agent therapy with a loading dose, a trastuzumab 4 mg/kg followed by 2 mg/kg weekly was recommended. The patient also received 60 Gy radiotherapy. Six months after the second line treatment, the breast tumor disappeared and only a scar remained on the chest wall and axilla. CT showed no lung tumors. During the trastuzumab treatment, no adverse effect was observed. Her performance status improved to zero, and she is alive and free from the disease 24 months after the disappearance of the tumor.}, } @article {pmid17146163, year = {2006}, author = {Kato, M and Oda, K and Kubota, T and Satake, H and Kato, M and Nimura, Y}, title = {Non-palpable and non-invasive ductal carcinoma with bloody nipple discharge successfully resected after cancer spread was accurately diagnosed with three-dimensional computed tomography and galactography.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {4}, pages = {360-363}, doi = {10.2325/jbcs.13.360}, pmid = {17146163}, issn = {1340-6868}, mesh = {Adult ; Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/*pathology/surgery ; Female ; Humans ; Imaging, Three-Dimensional ; Mammary Glands, Human/*pathology ; Mastectomy, Segmental ; Nipples/*metabolism ; Tomography, X-Ray Computed ; }, abstract = {A case of ductal carcinoma in situ (DCIS) that was treated by partial mastectomy is reported. The operation was performed after accurate estimation of cancer spread by three-dimensional computed tomography (3D-CT). The patient was a 39-year-old woman without a palpable lump who had a bloody nipple discharge. Ultrasonography showed distended mammary ducts with intraductal components. Fine needle aspiration cytology revealed ductal carcinoma. Galactography showed two subsegmental ducts and peripheral branches in the upper-inner quadrant of the right breast. 3D-CT depicted a well enhanced segmental-clumped lesion including two subsegments of a duct lobular system shown in galactograms. DCIS was diagnosed and partial mastectomy following the video assisted thoracoscopic surgery (VATS) marker insertion was performed, after cancer spread was accurately diagnosed by 3D-CT guidance. DCIS resected by minimally sufficient partial mastectomy with negative surgical margins was diagnosed histopathologically.}, } @article {pmid17145955, year = {2006}, author = {Pion, M and Granelli-Piperno, A and Mangeat, B and Stalder, R and Correa, R and Steinman, RM and Piguet, V}, title = {APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection.}, journal = {The Journal of experimental medicine}, volume = {203}, number = {13}, pages = {2887-2893}, pmid = {17145955}, issn = {0022-1007}, support = {N01AI40045/AI/NIAID NIH HHS/United States ; AI40045/AI/NIAID NIH HHS/United States ; }, mesh = {APOBEC-3G Deaminase ; Antiviral Restriction Factors ; Base Sequence ; Carrier Proteins/genetics/metabolism/physiology ; Cell Differentiation/drug effects/genetics ; Cell Line ; Cytidine Deaminase ; Cytosine Deaminase/genetics/metabolism/*physiology ; DNA, Viral/genetics ; Dendritic Cells/drug effects/metabolism/*virology ; Flow Cytometry ; Gene Expression ; Green Fluorescent Proteins/genetics/metabolism ; HIV-1/genetics/*growth & development ; HeLa Cells ; Humans ; Jurkat Cells ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/genetics ; Molecular Sequence Data ; Monocytes/*cytology ; Nucleoside Deaminases/genetics/metabolism/*physiology ; Point Mutation ; RNA, Small Interfering/genetics ; Repressor Proteins/genetics/metabolism/*physiology ; Sequence Homology, Nucleic Acid ; Transfection ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; Viral Envelope Proteins/genetics ; Virus Replication/genetics ; }, abstract = {HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA-mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5alpha, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.}, } @article {pmid17144425, year = {2006}, author = {Ivković-Kapicl, T and Knezević-Usaj, S and Panjković, M and Nincić, D and Mastilović, K}, title = {[The influence of aging on pathologic and immunobiologic parameters of invasive ductal breast carcinoma].}, journal = {Vojnosanitetski pregled}, volume = {63}, number = {11}, pages = {921-927}, doi = {10.2298/vsp0611921i}, pmid = {17144425}, issn = {0042-8450}, mesh = {Adult ; Aged ; *Aging ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {BACKGROUND/AIM: Most human cancers, including breast one, increase in frequency with aging. The aim of this study was to explore the hypothesis that aging also alters breast cancer biology.

METHODS: The study included 120 women with primary invasive ductal carcinoma of the breast. We correlated the patients age and diagnosis with the commonly used clinical, pathological factors and newer tumor biomarkers. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, estrogen (ER), progesterone (PR) receptors, and angiogenesis.

RESULTS: In our study, the patients with axillary lymph node metastases and negative steroid hormone receptors (ER and PR) were significantly younger than the patients with nodal involvement and positive hormone receptors. There was also a significant association between the patients age, diagnosis and angiogenesis. No association was found between the patients age and tumour size, histological grade, p53, c-erbB-2, and Ki-67.

CONCLUSION: The results of our study supported only partially the hypothesis that the breast cancer biology is significantly affected by a patient's age.}, } @article {pmid17139431, year = {2006}, author = {Naito, Y and Suda, K and Nobukawa, B and Kinoshita, H and Kojiro, M}, title = {Histopathological study of invasive ductal carcinoma (IDC) of the pancreas without associated cancerous occlusion of the main pancreatic duct.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {13}, number = {6}, pages = {556-561}, doi = {10.1007/s00534-006-1112-6}, pmid = {17139431}, issn = {0944-1166}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/immunology/*pathology ; Constriction, Pathologic ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/immunology ; Male ; Middle Aged ; Pancreatic Ducts/*pathology ; Pancreatic Neoplasms/immunology/*pathology ; }, abstract = {BACKGROUND/PURPOSE: [corrected] Invasive ductal carcinoma (IDC) of the pancreas may be associated with cancerous occlusion of the main pancreatic duct (MPD) in its growth process, but at quite low a frequency; there are patients who do not develop this occlusion.

METHODS: This study examined the histological features of surgical specimens from 8 patients with IDC without MPD occlusion, in comparison to 32 patients with IDC with this occlusion (controls). The pancreatic duct was identified by confirming the presence of mural elastic fibers on the wall of the pancreatic duct. Immunohistochemical staining was done with Ki-67 antibody.

RESULTS: The frequency of IDC without MPD occlusion was very low (5.0% [2/40] patients at Kurume University and 3.1% [4/126] patients at Juntendo University). The number of intraductal carcinoma components was 1.5 +/- 1.1 per specimen in the IDCs without occlusion and 5.9 +/- 2.4 in the controls (P < 0.001). The Ki-67 labeling index was 18.0 +/- 11.7% in the IDCs without occlusion and 30.0 +/- 12.1% in the controls (P < 0.05). The number of intraductal carcinoma components and the Ki-67 labeling index were significantly lower in the IDCs without occlusion than in the controls.

CONCLUSIONS: Our findings suggested that these two types of IDC could have different biological features.}, } @article {pmid17139139, year = {2006}, author = {Tozaki, M and Fukuda, K and Suzuki, M}, title = {Dynamic high-spatial-resolution MR imaging of invasive ductal carcinoma: influence of histological scirrhous component on MR descriptors.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {5}, number = {3}, pages = {137-146}, doi = {10.2463/mrms.5.137}, pmid = {17139139}, issn = {1347-3182}, mesh = {Adenocarcinoma, Scirrhous/*pathology ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness/diagnosis ; Retrospective Studies ; }, abstract = {PURPOSE: The purpose of this study was to assess the relationship between the amount of scirrhous component in invasive ductal carcinoma and its MR characteristics.

MATERIALS AND METHODS: We retrospectively reviewed 71 consecutive patients with invasive ductal carcinoma smaller than 25 mm (average, 16.6 mm) in diameter. The scirrhous component was defined as invasive foci in small clusters of cancer cells showing desmoplasia. Invasive ductal carcinoma was subclassified into 3 groups in accordance with the amount of the scirrhous component (scirrhous component degree; SCD): SCD I (scirrhous component less than 20%), SCD II (intermediate), and SCD III (more than 80%). Dynamic magnetic resonance (MR) imaging was performed using volumetric interpolated sequence. Prior to dynamic study, T2*-weighted first-pass perfusion images were obtained before, during, and after bolus injection of 0.1 mmol Gd-DTPA/kg.

RESULTS: Twenty-eight lesions were classified as SCD I, 14 as SCD II, and 29 as SCD III. Mass margin and signal intensity loss in the perfusion study were significantly different among the 3 SCD groups (P<0.001). The kinetic patterns were significantly different among the 3 SCD groups (P=0.04), and between SCD I/II and SCD III (P=0.03). The presence of enhancing internal septations was significantly different between SCD I/II and SCD III carcinomas (P=0.05). Central enhancement was only observed in SCD I carcinoma (4%; 3/71).

CONCLUSION: The histological predominance of the scirrhous component in invasive ductal carcinoma may be one explanation for the differences in morphologic and kinetic patterns on MR imaging.}, } @article {pmid17130547, year = {2006}, author = {Lo, J and Peng, RH and Barker, T and Xia, CQ and Clare-Salzler, MJ}, title = {Peptide-pulsed immature dendritic cells reduce response to beta cell target antigens and protect NOD recipients from type I diabetes.}, journal = {Annals of the New York Academy of Sciences}, volume = {1079}, number = {}, pages = {153-156}, doi = {10.1196/annals.1375.023}, pmid = {17130547}, issn = {0077-8923}, mesh = {*Adoptive Transfer ; Animals ; Antigens/*immunology ; Cell Division/drug effects/immunology ; Cells, Cultured ; Dendritic Cells/*immunology/transplantation ; Diabetes Mellitus, Type 1/*immunology/*prevention & control ; Female ; Glutamate Decarboxylase/immunology ; Immune Tolerance ; Insulin/pharmacology ; Islets of Langerhans/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Peptide Fragments/chemistry/immunology/pharmacology ; Spleen/cytology/metabolism ; T-Lymphocytes/immunology/physiology ; }, abstract = {Our previous work demonstrated peptide-pulsed mature myeloid dendritic cells (DC) presenting beta cell antigens induce tolerance. Here we determine whether immature DC (iDC) presenting dominant (insulin beta9-23 chain, proinsulin C19-A3) or ignored (glutamic acid decarboxylase 65(78-97)) antigen determinants promote tolerance. Nonobese diabetic (NOD) mice were given injections of either unpulsed or peptide-pulsed myeloid iDC beginning at 9 weeks of age for 3 consecutive weeks. Diabetes incidence in recipients of unpulsed iDC was comparable to unmanipulated animals (approximately 80%), whereas GAD65(78-97) pulsed iDC recipients were protected from the disease (P = 0.05). We also analyzed splenic T cell proliferation responses to the panel of studied peptides in diabetic and nondiabetic recipients. When stimulated with insulin or proinsulin peptide, nondiabetic mice receiving the peptide-pulsed iDC had a 21- to 31-fold or 3.9- to 9.0-fold reduction in T cell response, respectively, as compared to the response of diabetic unpulsed recipients. However, only a 2.6- to 3.1-fold reduction in response to beta chain peptide, and a 1.5- to 3.4-fold reduction in proinsulin response were observed in diabetic mice receiving peptide-pulsed iDC. The reduction was not specific to the immunizing peptide, as reduced proliferation was observed to other diabetes-target peptides. We conclude that protective iDC-based therapies require target antigen presentation, and ignored determinants may be preferable perhaps due to an available naïve T cell repertoire. In addition, iDC presenting peptides induce a nonspecific reduction in T cell responses to beta cell antigens, possibly through the induction of regulatory T cells.}, } @article {pmid17126942, year = {2007}, author = {Seifert, L and Chollet, D and Rouard, A}, title = {Swimming constraints and arm coordination.}, journal = {Human movement science}, volume = {26}, number = {1}, pages = {68-86}, doi = {10.1016/j.humov.2006.09.003}, pmid = {17126942}, issn = {0167-9457}, mesh = {Analysis of Variance ; Body Height ; Body Size ; Fatigue ; Female ; Humans ; Male ; Posture ; *Psychomotor Performance ; *Swimming ; Video Recording ; }, abstract = {Following Newell's concept of constraint (1986), we sought to identify the constraints (organismic, environmental and task) on front crawl performance, focusing on arm coordination adaptations over increasing race paces. Forty-two swimmers (15 elite men, 15 mid-level men and 12 elite women) performed seven self-paced swim trials (race paces: as if competitively swimming 1500m, 800m, 400m, 200m, 100m, 50m, and maximal velocity, respectively) using the front crawl stroke. The paces were race simulations over 25m to avoid fatigue effects. Swim velocity, stroke rate, stroke length, and various arm stroke phases were calculated from video analysis. Arm coordination was quantified in terms of an index of coordination (IdC) based on the lag time between the propulsive phases of each arm. This measure quantified three possible coordination modes in the front crawl: opposition (continuity between the two arm propulsions), catch-up (a time gap between the two arm propulsions) and superposition (an overlap of the two arm propulsions). With increasing race paces, swim velocity, stroke rate, and stroke length, the three groups showed a similar transition in arm coordination mode at the critical 200m pace, which separated the long- and mid-pace pattern from the sprint pace pattern. The 200m pace was also characterized by a stroke rate close to 40strokemin(-1). The finding that all three groups showed a similar adaptation of arm coordination suggested that race paces, swim velocity, stroke rate and stroke length reflect task constraints that can be manipulated as control parameters, with race paces (R(2)=.28) and stroke rate (R(2)=.36) being the best predictors of IdC changes. On the other hand, only the elite men reached a velocity greater than 1.8ms(-1) and a stroke rate of 50strokemin(-1). They did so using superposition of the propulsion phases of the two arms, which occurred because of the great forward resistance created when these swimmers achieved high velocity, i.e., an environmental constraint. Conversely, the elite women and mid-level men had shorter stroke lengths and maintained a time gap between the propulsions of the two arms throughout the increase in paces, with gender and expertise explaining 9% and 8.3% of the IdC changes, respectively. These results indicate that arm coordination cannot be interpreted solely from the IdC value but should be considered from the perspective of task, environmental, and organismic constraints. These constraints can serve as control parameters in experiments aimed at gaining insight into changes in arm coordination during the front crawl. In this context, catch-up coordination, which is often considered as a mistake, was seen to be an adaptation to a relative constraint.}, } @article {pmid17126830, year = {2007}, author = {Rodríguez-Pérez, JM and Fragoso, JM and Alvarez-León, E and Martínez-Rodríguez, N and Gallardo, GJ and Inés-Real, S and Granados, J and Reyes, PA and Vargas-Alarcón, G}, title = {MHC class II genes in Mexican patients with idiopathic dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {82}, number = {1}, pages = {49-52}, doi = {10.1016/j.yexmp.2006.10.002}, pmid = {17126830}, issn = {0014-4800}, mesh = {Cardiomyopathy, Dilated/*genetics ; *Genes, MHC Class II ; *Genetic Predisposition to Disease ; Humans ; Mexico ; Polymerase Chain Reaction ; }, abstract = {The purpose of the present study was to evaluate the relationship between class II major histocompatibility complex (MHC) genes (HLA-DR and HLA-DQB) and the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The HLA-DR and DQB alleles were analyzed in 53 patients with IDC and 99 ethnically matched healthy controls using the polymerase chain reaction-sequence specific oligonucleotides (PCR-SSO) technique. IDC patients showed increased frequencies of HLA-DR4 (pC=0.02, OR=1.87), HLA-DQB1*0301 (pC=0.02, OR=1.92) and HLA-DQB1*0302 (pC=0.02, OR=1.87) when compared to healthy controls. On the other hand, IDC patients also showed decreased frequencies of HLA-DR11 allele (pC=0.03, OR=0.26) and HLA-DQB1*0201 (pC=0.04, OR=0.41). These data suggest that variation in class II HLA alleles could be a genetic factor involved in the susceptibility to IDC of the Mexican Mestizo population.}, } @article {pmid17125718, year = {2006}, author = {Fernández-Portales, J and Valdesuso, R and Carreras, R and Jiménez-Candil, J and Serrador, A and Romaní, S}, title = {[Right versus left radial artery approach for coronary angiography. Differences observed and the learning curve].}, journal = {Revista espanola de cardiologia}, volume = {59}, number = {10}, pages = {1071-1074}, doi = {10.1157/13093986}, pmid = {17125718}, issn = {0300-8932}, mesh = {Age Factors ; Aged ; Cardiac Catheterization/*methods ; Coronary Angiography/adverse effects/*methods ; Female ; Fluoroscopy ; Humans ; Learning ; Logistic Models ; Male ; Prospective Studies ; *Radial Artery/anatomy & histology ; Risk Factors ; }, abstract = {There are anatomical differences between right and left radial artery approaches for coronary catheterization that could influence application of the technique. We present the results of a randomized study that compared the effectiveness of the two approaches and identified factors associated with failure of the procedure. The study involved 351 consecutive patients: a left radial approach was used in 180, and a right radial approach, in 171. The procedure could not be completed using the initial approach selected in 15 patients (11 right radial vs. 4 left radial; P=.007). Use of a right radial approach, lack of catheterization experience, patient age >70 years, and the absence of hypertension were found to be independently associated with prolonged fluoroscopy duration and failure using the initial approach. Use of the right radial approach in patients aged over 70 years was associated with a 6-fold increase in the risk of an adverse event. Consequently, use of the right radial approach should be avoided in patients aged over 70 years when trainee practitioners are on the learning curve.}, } @article {pmid17122512, year = {2006}, author = {Ban, S and Naitoh, Y and Mino-Kenudson, M and Sakurai, T and Kuroda, M and Koyama, I and Lauwers, GY and Shimizu, M}, title = {Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: its histopathologic difference between 2 major types.}, journal = {The American journal of surgical pathology}, volume = {30}, number = {12}, pages = {1561-1569}, doi = {10.1097/01.pas.0000213305.98187.d4}, pmid = {17122512}, issn = {0147-5185}, mesh = {Adenocarcinoma, Mucinous/classification/metabolism/*pathology ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Carcinoma, Pancreatic Ductal/classification/metabolism/*pathology ; Carcinoma, Papillary/classification/metabolism/*pathology ; Cell Transformation, Neoplastic/*pathology ; Female ; Gastric Mucosa/metabolism/pathology ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Middle Aged ; Mucin 5AC ; Mucins/metabolism ; Pancreatic Neoplasms/classification/metabolism/*pathology ; }, abstract = {Intraductal papillary mucinous neoplasm (IPMN) is a unique pancreatic neoplasm developing in the ductal system. Two major histologic subtypes have been reported, that is the gastric type and the intestinal type. However, their histopathologic features, especially those of the gastric type, have not been fully described. To evaluate the features of these two types and refine their differences, we analyzed 80 IPMNs including 50 cases of the gastric type and 30 cases of the intestinal type with mucin immunohistochemistry. By defining a main duct-type lesion as predominantly involving the main pancreatic duct with or without branch ducts, and a branch duct-type lesion as exclusively centered on branch ducts or consisting of a collection of small cystic lesions, gastric-type IPMNs were mostly branch duct-type lesions (98%), whereas the intestinal-type IPMNs were usually main duct type (73%). The histologic grade of the intestinal type was generally higher than that of the gastric type. The intestinal type was also characterized by frequent intraluminal nodular growth, and severe atrophy and fibrosis of the surrounding parenchyma with mucous lake formation. In contrast, pyloric glandlike structures at the base of the papillae and pancreatic intraepithelial neoplasia (PanIN)-like complexes were more frequently observed in the gastric type. A significant difference was observed between the gastric type and the intestinal type with regard to all the above features (P<0.05). Seven cases (23%) of the intestinal type were associated with an invasive adenocarcinoma (6 mucinous and 1 ductal), versus only 1 case (2%) of the gastric type (invasive ductal carcinoma). All cases of both gastric and intestinal types expressed MUC5AC; however, high immunolabeling scores for MUC2 were mostly observed in the intestinal type (P<0.05). In conclusion, gastric and intestinal types of IPMNs have distinct histopathologic features and mucin profiles, suggesting that they may follow different biologic pathways.}, } @article {pmid17120733, year = {2006}, author = {Ding, Y and Ruan, Q}, title = {The value of p63 and CK5/6 expression in the differential diagnosis of ductal lesions of breast.}, journal = {Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban}, volume = {26}, number = {4}, pages = {405-407}, pmid = {17120733}, issn = {1672-0733}, mesh = {Breast Diseases/diagnosis/metabolism ; Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal, Breast/*diagnosis/metabolism ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/diagnosis ; Humans ; Immunohistochemistry ; Keratin-5/*biosynthesis ; Keratin-6/*biosynthesis ; Membrane Proteins/*biosynthesis ; Papilloma, Intraductal/diagnosis/metabolism ; Predictive Value of Tests ; }, abstract = {In order to explore the value of p63, smoothmuscle actin (alpha-SMA) and cytokeratin 5/6 (CK5/6) in the differential diagnosis of ductal lesions of breast, 88 tissue specimens of ductal lesions of breast were collected and examined histologically by HE staining. By using immunohistochemistry, the expression of p63, alpha-SMA and CK5/6 was detected. The results showed that in 38 cases of benign breast lesions, the proliferating cells were all positive for p63 and alpha-SMA. In 19 cases of ductal carcinoma in situ (DCIS) and 7 cases of intraductal papillary carcinoma, alpha-SMA positive cells formed a layer of continuous embroider-shaped structure and the p63 positive cells formed a layer of evenly separated embroider-shaped structure around the ducts. There was no cross-reaction between p63 and interstitial myofibroblasts and vascular smooth muscle cells. In 38 cases of benign breast lesions, the positive rate of CK5/6 expression was 100%. In 5 cases of atypical ductal hyperplasia, there were few positive cells in the ducts. In 19 cases of CDIS, no tumor cells expressed CK5/6. In 19 cases of invasive ductal carcinoma, almost no CK5/6 was detectable. It was suggested that p63 could serve as a novel specific marker for the identification of breast myoepithelial cells. CK5/6 is of value in differentiating ductal proliferation of varying degrees, especially in the differentiation between cancerous and non-cancerous changes. Simultaneous detection of p63, CK5/6 and alpha-SMA can help increase the diagnostic accuracy of breast diseases.}, } @article {pmid17119686, year = {2006}, author = {Menezes, MV and Cestari, AL and Almeida, O and Alvarenga, M and Pinto, GA and Gurgel, MS and Souza, GA and Zeferino, LC}, title = {Protein expression of c-erbB-2 and p53 in normal ducts, ductal carcinoma in situ and invasive carcinoma of the same breast.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {124}, number = {3}, pages = {121-124}, doi = {10.1590/s1516-31802006000300002}, pmid = {17119686}, issn = {1516-3180}, mesh = {Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cross-Sectional Studies ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Neoplasm Invasiveness ; Odds Ratio ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {CONTEXT AND OBJECTIVE: Breast cancer is thought to derive from progressively aberrant, non-invasive breast lesions, but it is not known exactly how invasive breast cancer develops from these lesions. The aim of this study was to verify the changes in c-erbB-2 and p53 protein expression between non-neoplastic ducts, ductal carcinoma in situ and invasive ductal carcinoma found in the same breast.

DESIGN AND SETTING: This was a cross-sectional study at Centro de Atenção Integral à Saúde da Mulher, Campinas, Brazil.

METHODS: Fifty-six women with invasive ductal carcinoma and ductal carcinoma in situ in the same breast were included. The expression of c-erbB-2 and p53 proteins was assessed in non-neoplastic and neoplastic cells using immunohistochemical techniques.

RESULTS: The c-erbB-2 protein was absent in non-neoplastic ducts but was present in 46% and 36% of in situ and invasive carcinoma components, respectively. Only 2% of non-neoplastic ducts, and 18% and 16% of ductal carcinoma in situ and invasive carcinoma components, respectively, were positive for p53 protein. No significant difference in c-erbB-2 and p53 protein expression was observed between in situ and invasive components. The nuclear grade agreement between in situ and invasive carcinoma was very good.

CONCLUSIONS: The invasiveness of ductal carcinoma in situ seems to be independent of the Her-2/neu and TP53 genes. The general features of an occurrence of breast carcinoma are formulated at the outset of carcinogenesis, and the Her-2/neu and TP53 genes are involved.}, } @article {pmid17117186, year = {2007}, author = {Badenhorst, D and Norton, GR and Sliwa, K and Brooksbank, R and Essop, R and Sareli, P and Woodiwiss, AJ}, title = {Impact of beta2-adrenoreceptor gene variants on cardiac cavity size and systolic function in idiopathic dilated cardiomyopathy.}, journal = {The pharmacogenomics journal}, volume = {7}, number = {5}, pages = {339-345}, doi = {10.1038/sj.tpj.6500426}, pmid = {17117186}, issn = {1470-269X}, mesh = {Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/drug therapy/*genetics/pathology/physiopathology ; Cardiotonic Agents/therapeutic use ; Cardiovascular Agents/pharmacology/*therapeutic use ; Case-Control Studies ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Drug Therapy, Combination ; Female ; Furosemide/therapeutic use ; Gene Frequency ; Genetic Predisposition to Disease ; Haplotypes ; Heart Ventricles/pathology ; Humans ; Male ; Middle Aged ; *Polymorphism, Restriction Fragment Length ; Prospective Studies ; Receptors, Adrenergic, beta-2/*genetics ; Risk Factors ; Stroke Volume/drug effects/genetics ; Systole ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects/*genetics ; Ventricular Remodeling/drug effects/*genetics ; }, abstract = {In heart failure, the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenoreceptor (beta2-AR) gene are associated with exercise-capacity, clinical outcomes and response to beta-AR blocker therapy. Whether beta2-AR gene variants mediate these effects in-part through an impact on cardiac structural remodeling and pump function independent of the effects of beta-blockers is uncertain. We evaluated whether the Arg16Gly and Gln27Glu variants of the beta2-AR gene predict left ventricular ejection fraction (LVEF) and LV end diastolic diameter (LVEDD) in patients with idiopathic dilated cardiomyopathy (IDC) before and 6 months after receiving standard medical therapy other than beta-AR blockers. In all, 394 patients with IDC and 393 age and gender-matched controls were genotyped for the beta2-AR gene variants using restriction-fragment length polymorphism-based techniques. LVEF and dimensions were determined in 132 patients (of whom 71 were newly diagnosed) both at baseline and after 6 months. Genotype of neither variant was associated with the presence of IDC. Moreover, beta2-AR genotype did not determine LVEF or LV dimensions prior to initiating therapy. After 6 months of therapy, LVEF increased by 7.1+/-1.0 absolute units (P<0.0001) and LVEDD decreased by 0.27+/-0.06 cm (P<0.02). Adjusting for baseline values as well as gender, age, and type of angiotensin-converting enzyme inhibitor therapy received, genotype was associated with neither final LVEF and LVEDD, nor change in LVEF and LVEDD. In conclusion, these data suggest that in heart failure, the functional Arg16Gly and Gln27Glu variants of the beta2-AR gene have no independent effect on adverse structural remodeling and pump function.}, } @article {pmid17117084, year = {2006}, author = {Punch, GE and Burtis, MT and Brown, JM}, title = {Incidental detection of previously undiagnosed primary breast carcinoma with a gallium-67 scan performed for evaluation of occult infection.}, journal = {Clinical nuclear medicine}, volume = {31}, number = {12}, pages = {817-819}, doi = {10.1097/01.rlu.0000247745.19585.e3}, pmid = {17117084}, issn = {0363-9762}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal/*diagnostic imaging ; *Citrates ; Female ; *Gallium ; Humans ; Incidental Findings ; Infections/*diagnostic imaging ; Middle Aged ; Nephritis/*diagnostic imaging ; Radionuclide Imaging ; Radiopharmaceuticals ; *Whole Body Imaging ; }, abstract = {A 63-year-old female patient with a recent left posterior cerebral artery infarction and pyelonephritis presented with persistent fevers despite adequate intravenous antibiotic therapy. Whole-body gallium-67 scintigraphy was performed to evaluate for occult infection. Tracer accumulated bilaterally in the kidneys consistent with the previously diagnosed pyelonephritis. Relatively intense uptake was also noted in the area of a known occipitoparietal infarct. Incidentally noted was an abnormal focus of increased tracer uptake in the retroareolar region of the right breast. Subsequent guided core biopsy of the right breast mass demonstrated a previously undiagnosed invasive ductal carcinoma.}, } @article {pmid17117080, year = {2006}, author = {Duch, J and Fuster, D and Ortín, J and Setoain, X and Pons, F}, title = {Bilateral Paget disease of the calcaneus diagnosed by conventional bone scintigraphy.}, journal = {Clinical nuclear medicine}, volume = {31}, number = {12}, pages = {808-809}, doi = {10.1097/01.rlu.0000247783.43949.c1}, pmid = {17117080}, issn = {0363-9762}, mesh = {Aged, 80 and over ; Calcaneus/*diagnostic imaging ; Female ; Humans ; Osteitis Deformans/*diagnostic imaging ; Radionuclide Imaging ; Radiopharmaceuticals ; *Technetium Tc 99m Medronate ; *Whole Body Imaging ; }, abstract = {An 85-year-old woman who had an invasive ductal carcinoma of the breast and elevated alkaline phosphatases (420 U/L) was referred for Tc-99m MDP bone scintigraphy for initial evaluation of skeletal metastases. Bone symptoms were limited to chronic pain in both knees. A bone scan revealed pagetoid findings in both calcanei. Feet and toes on plain x-rays of the calcaneus were unremarkable. Findings were stable in the 2-year follow up, excluding other potential diagnosis as extensive metastases or stress fractures.}, } @article {pmid17115108, year = {2007}, author = {Figueiredo, JC and Ennis, M and Knight, JA and McLaughlin, JR and Hood, N and O'Malley, F and Andrulis, IL and Goodwin, PJ}, title = {Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study.}, journal = {Breast cancer research and treatment}, volume = {105}, number = {1}, pages = {69-80}, doi = {10.1007/s10549-006-9433-3}, pmid = {17115108}, issn = {0167-6806}, mesh = {Adult ; Age of Onset ; Breast Neoplasms/*diagnosis/pathology/therapy ; Cohort Studies ; Female ; Humans ; Middle Aged ; Models, Genetic ; Ontario ; Ovarian Neoplasms/*diagnosis/*pathology/therapy ; Prognosis ; Registries ; Risk ; Treatment Outcome ; }, abstract = {PURPOSE: The objective of this study was to examine the association of: (i) diagnosis at age
PATIENTS AND METHODS: Consenting female participants in the population-based Ontario Familial Breast Cancer Registry diagnosed with primary invasive BC between 1996 and 1998 were followed prospectively until 2005.

RESULTS: Among 967 women, 105 were
CONCLUSION: Women diagnosed with BC at age
MATERIALS AND METHODS: Between January 1983 and December 2002, 25 patients with clinically or mammographically detected DCIS were treated by BCS-RT. One patient was diagnosed with bilateral DCIS. Thirteen cases (50%) had symptomatic lesions at presentation. All 26 cases of 25 patients underwent BCS such as lumpectomy, partial mastectomy or quadrantectomy. All of them received whole breast irradiation to a median dose of 50.4 Gy. Twenty-four cases (92.3%) received a boost to the tumor bed for a median total dose of 59.4 Gy. The median follow up period was 67 months (range: 38 to 149 months).

RESULTS: Two cases (7.7%) experienced ipsilateral breast tumor recurrence (IBTR) after BCS-RT. The histology results at the time of IBTR showed invasive ductal carcinoma (IDC), and the median time to IBTR was 25.5 months. On the univariate analysis, there were no significant factors associated with IBTR in the DCIS patients. The three-year local recurrence free survival rate was 96.0% and the overall survival rate was 96.3%.

CONCLUSION: After the treatment for DCIS, the IBTR rate in our study was similar to other previous studies. Considering that we included patients who had many symptomatic lesions, close or positive margins and less that complete early data, our result is comparable to the previous studies. We could not find the prognostic significant factors associated with IBTR after BCS-RT. A longer follow up period with more patients would be required to evaluate the role of any predictive factors and to confirm these short-term results.}, } @article {pmid20591227, year = {2003}, author = {Kaku, Y and Yoshimura, S and Kokuzawa, J and Sakai, N}, title = {Clinical and Angiographic Results of Intra-Aneurysmal Embolization for Cerebral Aneurysms and Histopathological Findings in an Aneurysm Treated with GDC.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {9}, number = {Suppl 1}, pages = {35-40}, pmid = {20591227}, issn = {1591-0199}, abstract = {We describe follow-up clinical and angiographic results in patients with cerebral aneurysms treated with IDC or GDC. In 175 patients, 116 patients with ruptured aneurysm and 59 patients with non-ruptured aneurysm who underwent endovascular occlusion of aneurysms, there was no mortality and nine cases (4.7%) with morbidity in the periprocedural period. During follow up period, four cases (2.3%) experienced bleeding, and three cases (1.7%) experienced thrombo-embolic events. On the follow-up angiograms (median angiographic follow-up period 24.8 months), 12.5% of incompletely obliterated aneurysms exhibited progressive thrombosis, 20% remained unchanged and 67.5% showed aneurysmal recanalization or regrowth. Histological examination of a small ruptured A-com aneurysm treated seven months before harvesting, demonstrated that formation of an incomplete endothelium- lined layer of connective tissue at the orifice, and no complete fibrous obliteration of the aneurysm lumen could be detected, various amounts of unorganized clot were still present in the center of the aneurysm. Coil embolization is a safe treatment for cerebral aneurysms with a lower incidence of peri-procedural morbidity, wheareas follow-up results are less satisfactory in cases involving incompletely obliterated lesions.}, } @article {pmid20667233, year = {2000}, author = {Nishizawa, T and Terada, K and Matsuyama, N}, title = {Transvenous detachable coil embolization of direct & high-flow carotid-cavernous fistula. Alternative of transarterial detachable balloon embolization.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {6 Suppl 1}, number = {Suppl 1}, pages = {117-124}, pmid = {20667233}, issn = {1591-0199}, abstract = {We encountered 8 cases of high-flow and direct carotid cavernous fistula (CCF) since 1994. Four patients were treated with transarterial fistula occlusions using detachable balloons before 1997. Complete obliteration of CCFs with preservation of internal carotid artery (ICA) were achieved in all 4 cases using each one balloon. Three cases were approached to the fistulas via the percutaneous transfemoral approach, but one aged patient needed a direct carotid puncture because of her tortuous vessels. Meanwhile, transvenous embolizations with detachable coils (DCs); Guglielmi detachable coil (GDC), interlocking detachable coil (IDC) and fibered platinum coil were attempted in four cases after 1997; in 2 cases after failure of transarterial approach and in 2 as initial form of treatment. All 4 cases were successfully approached to the cavernous sinuses (CS) through the inferior petorosal sinus (IPS). At first we intended to block dangerous outflow points for the superior ophthalmic vein (SOV), cortical venous reflux (CVR) and contra-lateral CS. And then obliteration of the fistulas were performed with tight packing of GDCs covering the outside of the ICA. At this time, the arteriovenous shunts were disappeared abruptly, so we finished all procedure without occlusion of IPS.We compared the two methods and concluded that the transvenous embolizaton with DCs is an useful alternative of transarterial detachable balloon therapy of high flow CCF, especially when transarterial approach is difficult or proper balloons are not available.}, } @article {pmid20670546, year = {1999}, author = {Kaku, Y and Yoshimura, S and Hayashi, K and Ueda, T and Sakai, N}, title = {Follow-up study on intra-aneurysmal embolization for unruptured cerebral aneurysms.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {5 Suppl 1}, number = {}, pages = {89-92}, doi = {10.1177/15910199990050S116}, pmid = {20670546}, issn = {1591-0199}, abstract = {We describe follow-up clinical and angiographical results in patients with unruptured cerebral aneurysms treated with IDC or GDC. In 28 patients who underwent intra-aneurysmal occlusion for unruptured aneurysms, there were no permanent neurological deficits in the periprocedural period, while three transient neurological deficits were observed. On the angiograms obtained immediately after the procedure, complete aneurysmal occlusion was achieved in three patients (10.7%), a small neck remnant was detected in two cases (7.1%), a body filling in 12 cases (42.9%) and both of them were detected in 11 patients (39.3%). On the follow up angiograms (median angiographical follow-up period 15.6 months), 46.4% of incompletely obliterated aneurysms showed aneurysmal recanalization, and a incompletely embolized aneurysm ruptured 15 months after initial embolization. Detachable platinum coil embolization is a safe treatment for unruptured aneurysms with a lower incidence of peri-procedural morbidity, wheareas follow-up results are less satisfactory in cases involving incompletely obliterated lesions. With this limitation in mind, patients need to be very carefully chosen for GDC embolization and strict follow-up angiography is mandatory when a complete embolization is not achieved.}, } @article {pmid20673478, year = {1998}, author = {Makiuchi, T and Takasaki, K and Yamagami, M and Oda, H and Todoroki, K and Atsuchi, M and Kadota, K}, title = {A case of sigmoid sinus dural arteriovenous fistula after treated cavernous dural arteriovenous fistula.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {4 Suppl 1}, number = {}, pages = {219-222}, doi = {10.1177/15910199980040S145}, pmid = {20673478}, issn = {1591-0199}, abstract = {Transvenous embolization has been recommended recently as the primary treatment for symptomatic cavernous dural arteriovenous fistula (dural AVF). We present a case of sigmoid sinus dural AVF which developed after transvenous embolization of cavernous dural AVF. A 43-year-old man was admitted to our hospital because of left conjunctivill chemosis, exophthalmus and abducens nerve palsy. Cerebral angiograms showed left cavernous dural AVF fed by the bilateral internal and external carqtid arteries and draining into the enlarged left superior ophthalmic vein. Transfemoral approach in the cqvernous sinus via inferior petrosal sinus (IPS) was difficult because of the occlusive change of IPS. Then, direct canulation of the left superior ophthalmic vein and transvenous embolization using interlocking detachable coils (IDC) were performed. Dural AVF and clinical symptoms were disappeard rapidly after embolization. Six months later, follow-up cerebral angiograms showed development of a dural AVF in the left sigmoid sinus. The pathogenesis of dural AVF remains unclear. We suggest that injury to the sinus wall during endovascular procedures may have provoked the development of dural AVF in our case. Clinical and angiographical follow-up are important.}, } @article {pmid20673466, year = {1998}, author = {Nemoto, S and Iwama, J and Mayanagi, Y and Kirino, T}, title = {Coil Embolization of Cerebral Aneurysms. Experience with IDC and GDC.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {4 Suppl 1}, number = {}, pages = {159-164}, doi = {10.1177/15910199980040S133}, pmid = {20673466}, issn = {1591-0199}, abstract = {Coil embolization was performed in 86 cerebral aneurysm patients using two types of detachable platinum coils, IDC (Interlocking detachable coil) and GDC (Guglielmi electrical detachable coil). Results of IDC and GDC were compared. The occlusion rate of the aneurysm sac was similar. Coil compaction occurred frequent and early in cases with GDC. As clinical outcome, 94% of the patients in both group obtained good results. No bleeding or rebleeding occurred in the follow-up with IDC or GDC.}, } @article {pmid20673445, year = {1998}, author = {Hyodo, A and Kato, N and Anno, I and Sato, H and Nose, T and Okazaki, M and Kamezaki, T and Ito, M}, title = {Intra-aneurysmal Embolization for the Treatment of Cerebral Aneurysms Using Detachable Coils.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {4 Suppl 1}, number = {}, pages = {67-69}, doi = {10.1177/15910199980040S112}, pmid = {20673445}, issn = {1591-0199}, abstract = {From October 1993 to February 1998, intraaneurysmal embolization by endovascular treatment with detachable coils was performed for 41 cases of cerebral aneurysm. As a detachable coil, interlocking detachable coils (IDC) were used in the initial 15 cases and Guglielmi detachable coils (GDC) were used in the subsequent 26 cases. As for 15 cases treated with IDC, complete occlusion was performed in 9 cases, subtotal occlusion in 4 cases and partial occlusion in 2 cases. In one of the partial occluded cases, a coil compaction occurred 6 months after embolization. Distal emboli were recognized on CT after embolization in 3 cases, however, only one case was symptomatic. Intra-operative bleeding occurred in one case, but no obvious hemorrhage after coil embolization in any case. As for 26 cases treated with GDC, complete occlusion was performed in 18 cases, subtotal occlusion in 8 cases. In one case of basilar-tip aneurysm, a mild coil compaction occurred 6 months after embolization. Distal emboli were recognized on CT after embolization in 3 cases, however, only one case was symptomatic (minor stroke). No intra-operative bleeding and no obvious hemorrhage after coil embolization occurred in any case. From our experiences, treatment for poor-grade ruptured aneurysm is still difficult, but intraaneurysmal embolization for cerebral aneurysms using detachable coils is possible and a useful alternative, especially for surgically difficult aneurysms. The results of treatment of aneurysm with GDC are much better than those with IDC, so the indications for intra-aneurysmal embolization with GDC might increase in the future.}, } @article {pmid20678420, year = {1997}, author = {Koizumi, T and Kawano, T and Kazekawa, K and Kawaguchi, T and Honma, T and Kaneko, Y and Dosaka, A and Tabuchi, K and Iwata, H and Morikawa, N and Matsuda, S and Ikada, Y and Inoue, T}, title = {Embolization of aneurysms with a liquid material. An experimental study.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3 Suppl 2}, number = {}, pages = {205-207}, doi = {10.1177/15910199970030S244}, pmid = {20678420}, issn = {1591-0199}, abstract = {The authors evaluated the embolization effects on experimental aneurysm models with a liquid material. This material is a mixture of poly (HEMA-co-MMA), Iopamidol, water and a small amount of ethyl alcohol. We have satisfactorily treated over 30 cases of AVM with this material. Out of four solutions of different viscosity, we used the solution with the highest viscosity to prevent distal migration of the mixture. Glass models of aneurysms of 5 mm in diameter in pulsatile saline flow were embolized with the mixture under various conditions. When an IDC was placed in the aneurysm models, the mixture obliterated them completely and did not migrate out from the aneurysm models. In this experimental study, it is suggested that the liquid material appears to be useful in embolizing cerebral aneurysms safely.}, } @article {pmid20678412, year = {1997}, author = {Nakabayashi, K and Negoro, M and Itou, Y and Ichihara, K}, title = {Endovascular Approach vs Microsurgical Approach for Posterior Circulation Aneurysms.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3 Suppl 2}, number = {}, pages = {171-176}, doi = {10.1177/15910199970030S236}, pmid = {20678412}, issn = {1591-0199}, abstract = {We compare the results of detachable coil embolization with those of surgical clipping in patients with posterior circulation aneurysms. Surgical procedure was performed in 31 patients (basilar tip: 13 cases, SCA: 8 cases, basilar trunk: 1 case, VA: 9 cases). Thirty one aneurysms were treated by embolization with Guglielmi detachable coil (GDC) and interlocking detachable coil (IDC) (basilar tip: 14 cases, SCA: 1 case, basilar trunk: 6 cases, VA: 10 cases). In surgical cases, clinical outcome at discharge showed good recovery (GR) in 14 cases, moderate deficits (MD) in 11 cases, severe deficits (SD) in 2 cases, and dead (D) in 4 cases. In embolization cases, clinical outcome at discharge showed GR in 19 cases, MD in 4 cases, SD in 1 case, and D in 1 case. Embolization with detachable coils is less invasive than surgical clipping in the management of patients with posterior circulation aneurysms. Embolization with detachable coils in ruptured posterior circulation aneurysm cases at an early stage of SAH may improve clinical outcome.}, } @article {pmid20678407, year = {1997}, author = {Hyodo, A and Matsumaru, Y and Anno, I and Sato, H and Kato, N and Hashimoto, T and Yoshii, Y and Nose, T and Kamezaki, T and Okazaki, M}, title = {Intravascular neurosurgery for cerebral aneurysm using interlocking detachable coils.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3 Suppl 2}, number = {}, pages = {149-153}, doi = {10.1177/15910199970030S231}, pmid = {20678407}, issn = {1591-0199}, abstract = {Instead of the Guglielmi detachable coil (GDC; Target Therapeutics, Fremont, California), the interlocking detachable coil (IDC; Target Therapeutics, Fremont, California) was the only available detachable and retractable coil in Japan until February 1997. From October 1993 to February 1997, endovascular treatment with IDCs were attempted for 25 cases of cerebral aneurysm. Within 25 trials, 15 cases were treated by intraaneurysmal coil embolization, 9 cases by parent artery or proximal occlusion using IDCs and one case could not be treated due to anatomical problems of the aneurysm. As for 15 cases of intraaneurysmal coil packing, complete occlusion was performed in 9 cases, subtotal occlusion in 4 cases and partial occlusion in 2 cases. In one of the partial occluded cases, a coil compaction occurred 6 months after embolization. Distal emboli were recognized on CT after embolization in 3 cases, however, only one case was symptomatic. Intraoperative bleeding occurred in one case, but no obvious hemorrhage after coil embolization in any case. From our experiences, treatment for poor-grade ruptured aneurysm is still difficult, but intravascular surgery for cerebral aneurysms using IDC is possible and a useful alternative, especially for surgically difficult aneurysm.}, } @article {pmid20678401, year = {1997}, author = {Shibuya, T and Kushi, H and Kinoshita, K and Saito, T and Hayashi, N}, title = {Problems in endovascular procedures in acute ruptured intracranial aneurysms.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3 Suppl 2}, number = {}, pages = {121-124}, doi = {10.1177/15910199970030S225}, pmid = {20678401}, issn = {1591-0199}, abstract = {Fifteen patients with acute ruptured intracranial aneurysms were treated with interlocking detachable coil (IDC) embolization. All graded poorly, i.e., Hunt & Kosnik grades IV and V. Aneurysm occurred in the anterior circulation in 14 patients and at the basilar tip in one, of these, 13 were small and 2 large. The endovascular procedure was conducted in a transfemoral approach under local anesthesia. Aneurysmal obliteration was examined transitionally after embolization. Final outcome was evaluated using the Glasgow outcome scale (GOS). Total aneurysmal occlusion was observed immediately after IDC embolization in 11 patients. Two cases of coil migration to the parent artery occurred during endovascular procedure in patients with severe atherosclerosis. Aneurysmal rupture occurred during the endovascular procedure in a small internal carotid artery aneurysm when coil detachment failed. Follow-up angiography showed coil compaction in 2 patients, one patient experienced deterioration when the aneurysm ruptured. Eleven patients (73.3%) retained total aneurysmal occlusion and had no rebleeding. The overall GOS indicated good recovery in 5 patients, severe disability in 2, persistent vegetative state in 2, and death in 6. IDC embolization in severe acute ruptured intracranial aneurysm successfully prevented rebleeding, but our series was limited by the very small aneurysm size and the presence of severe atherosclerosis.}, } @article {pmid20678398, year = {1997}, author = {Kanaoka, N and Akashi, K and Kato, Y and Sano, H and Kanno, T and Ogura, Y and Takeshita, G and Katada, K}, title = {IDC Embolization of Aneurysms.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3 Suppl 2}, number = {}, pages = {110-113}, doi = {10.1177/15910199970030S222}, pmid = {20678398}, issn = {1591-0199}, abstract = {Embolization using IDC was carried out for 33 aneurysm cases in the last 3 years. The indication for the embolization was that the direct surgery was considered to be difficult, because of 1) technically impossible to do clipping, 2) aneurysm of the posterior fossa, 3) reject of patients. Regarding the location of aneurysm, 27 cases were seen in the anterior circulation, and 6 cases in the posterior circulation. Count of 33 cases, 11 cases were ruptured and 22 cases were non-ruptured. The procedure of embolization of aneurysms are generalized as compared to direct surgery, but there remain some technical problems. 33 cases in our series had no significant complication, except for one which had ruptured again. We emphasize that the weak point of IDC which was so hard, had no variations, especially if it happens to migrate during locking procedure. These complications can be prevented, if we use GDC(5,6,7) instead of IDC.}, } @article {pmid17353595, year = {1997}, author = {Mourad, WA and Devloo, S and Setrakian, S}, title = {Predictors of invasion in ductal carcinoma in Situ of the breast: The value of a scoring system.}, journal = {Annals of Saudi medicine}, volume = {17}, number = {4}, pages = {427-431}, doi = {10.5144/0256-4947.1997.427}, pmid = {17353595}, issn = {0256-4947}, abstract = {Ductal carcinoma in situ (DCIS) of the breast shows unpredictable association with invasive ductal carcinoma (IDC). Comedo DCIS (CDCIS) is more frequently associated with IDC than noncomedo DCIS (NCDCIS). We studied prognostic variables in 64 cases of DCIS to identify predictors of invasion. These factors included DCIS type and nuclear grade and two counts of the AgNOR silver staining technique for identification of ploidy and proliferative activity (PA) using two counts: mAgNOR for ploidy and pAgNOR for PA. The other factors included immunostaining of the lesions for epidermal growth factor receptors (EGFR), cathepsin-D (C-D), and the c-erbB-2 oncogene. The 34 cases associated with ICD had pAgNOR ranging from 3% to 36% (median 11%), whereas cases not associated with IDC had a pAgNOR range of 0% to 25% (median 5%; P=0.0001). The correlation between mAgNOR and the development of IDC was less statistically significant. The DCIS type and staining pattern for EGFR, C-D, and c-erbB-2 showed no statistical correlation of individual variables with the development of IDC. A scoring system adding the values of the seven variables was used. A score of 1-2 was given to each variable, depending on whether it was positive or negative. Lesions associated with IDC had a median total score of 8 (+/- 1.35 SD), whereas those lesions not associated with invasion had a median score of 4 (+/- 1.45 SD; P=0.0002). We conclude that proliferative activity analysis may play a significant role in predicting the invasive potential of DCIS. The use of a scoring system adding the sum of single prognostic indicators may provide more useful information regarding the prediction of invasive potential of DCIS than single indicators.}, } @article {pmid20678375, year = {1997}, author = {Kurata, A and Miyasaka, Y and Saegusa, H and Fujii, K and Kan, S}, title = {Treatment of a Small Hole Post-traumatic Carotid-Cavernous Fistula with a Non-Detachable Balloon Catheter. A Technical Note.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3}, number = {1}, pages = {87-90}, doi = {10.1177/159101999700300109}, pmid = {20678375}, issn = {1591-0199}, abstract = {Transarterial detachable balloon embolisation has become a well established primary treatment of post-traumatic carotid cavernous fistula (CCF) (1-3). However, in some instances due to the complexity of the fistula, the treatment can be difficult or impossibile. A simple and useful technique using a non-detachable balloon catheter to easily navigate the riilcrocatheter into the fistula via the transarterial route is discussed in this paper. The non-detachable balloon catheter allows easy navigation of the micro catheter into the small hole fistula, and complete occlusion of the fistula was obtained using one interlocking detachable coil (IDC) in the draining veins. The method of using a non-detachable balloon catheter to navigate a micro catheter into a fistula is relatively easy via the transarterial route.}, } @article {pmid20678372, year = {1997}, author = {Manabe, H and Fujita, S and Hatayama, T and Ohkuma, H and Suzuki, S and Yagihashi, S}, title = {Embolisation of Ruptured Cerebral Aneurysms with Interlocking Detachable Coils in Acute Stage. Acute IDC Embolisation for Ruptured Aneurysms.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {3}, number = {1}, pages = {49-63}, doi = {10.1177/159101999700300106}, pmid = {20678372}, issn = {1591-0199}, abstract = {SUMMARY: Twelve cases of ruptured cerebral aneurysm were treated in acute stage with interlocking detachable coils (IDC, Target Therapeutics, Fremont, California) and the outcome was assessed. IDCs were placed intra-aneurysm for intraaneurysmal occlusion, or intra-artery for proximal occlusion.

CASES: age 36-84 (mean; 60) y.o., 11 females and 1 male; 1, 5, 4 and 2 patients were categorised (Hunt and Hess) as grades 1, 2, 3 and 4 respectively. An intra-aneurysmal occlusion in ten cases and a proximal occlusion in two were performed on day 1-11 (mean 4). On angiograms and CT findings, the ruptured point seemed to have occluded in all cases. The occlusion rate was 100% in five cases, 95% in two, 90% in three, 80% in one, and less than 50% in one. There were two cases of technical complication, one a coil migration and the other an aneurysmal perforation with IDC. Their Glasgow Outcome Scale six months after embolisation was graded as good recovery in four cases, moderately disabled state in two, severely disabled state in one, and dead in five. Follow-up angiograms taken four to six months after embolisation showed an intra-aneurysmal coil compaction in five cases. Two of these were treated by a second embolisation or by neck clipping followed by aneurysmal resection, but another two were observed without any treatment and the last one died of rebleeding. Histological examination of the resected embolised aneurysm revealed slight organization around coils but no endothelialisation over the aneurysmal orifice. In our experience, coil embolisation with IDC for acute ruptured aneurysm is a promising means of preventing rerupture during subacute stage.}, } @article {pmid18250657, year = {1997}, author = {Fantini, S and Franceschini, MA and Gratton, E}, title = {Effective source term in the diffusion equation for photon transport in turbid media.}, journal = {Applied optics}, volume = {36}, number = {1}, pages = {156-163}, doi = {10.1364/ao.36.000156}, pmid = {18250657}, issn = {1559-128X}, abstract = {The Green's function for the diffusion equation is widely used to describe photon transport in turbid media. We have performed aseries of spectroscopy experiments on a number of uniform turbid media with different optical properties (absorption coefficient in the range 0.03-0.14 cm(-1), reduced scattering coefficient in the range 5-22 cm(-1)). Our experiments have been conducted in the frequency domain, where the measured parameters are the dc intensity (I(dc)), ac amplitude (I(ac)), and phase (?) of the light intensity wave. In an infinite medium, the Green's function predicts a linear dependence of ln(rI(dc)) and ? on the source-detector separation r. Our measurements show that the intercepts of these straight lines predicted by the Green's function do not agree with the experimental results. To reproduce the experimental results, we have introduced an effective photon source whose spatial extent and source strength depend on the optical properties of the medium. This effective source term has no effect on the slopes of the straight lines predicted by the Green'sfunction at large values of r.}, } @article {pmid18638882, year = {1996}, author = {Yoshimura, S and Hashimoto, N and Sampei, K and Nishi, S}, title = {Interlocking detachable coils for spontaneous vertebral arteriovenous fistula.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {3}, number = {3}, pages = {261-263}, doi = {10.1016/s0967-5868(96)90062-4}, pmid = {18638882}, issn = {0967-5868}, abstract = {We report a case of a spontaneous vertebral arteriovenous fistula treated with interlocking detachable coils (IDC). The patient had presented with paroxysmal dizziness and a cervical bruit. Angiography demonstrated a high flow arteriovenous fistula of the right extracranial vertebral artery. Embolisation was performed via the transarterial approach using 2 IDCs. The advantage of IDCs in the treatment of high flow arteriovenous fistulae is discussed.}, } @article {pmid17092958, year = {2007}, author = {Katz-Navon, T and Naveh, E and Stern, Z}, title = {The moderate success of quality of care improvement efforts: three observations on the situation.}, journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care}, volume = {19}, number = {1}, pages = {4-7}, doi = {10.1093/intqhc/mzl058}, pmid = {17092958}, issn = {1353-4505}, mesh = {*Efficiency, Organizational ; Health Policy ; Humans ; Organizational Objectives ; Quality Assurance, Health Care/*methods ; Safety Management ; }, abstract = {Why is the health care system still unable to achieve a breakthrough in its quality performance? This commentary offers three observations on the problem of the moderate success of quality of care improvement efforts. We based our discussion on theoretical models from management theory and research. We conclude that health care organizations invest efforts in quality improvement initiatives; however, there is a potential in improving the fit between these efforts and the specific problems these organizations face.}, } @article {pmid17091330, year = {2007}, author = {Ollila, DW and Klauber-DeMore, N and Tesche, LJ and Kuzmiak, CM and Pavic, D and Goyal, LK and Lian, J and Chang, S and Livasy, CA and Sherron, RF and Sartor, CI}, title = {Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively.}, journal = {Annals of surgical oncology}, volume = {14}, number = {2}, pages = {660-669}, doi = {10.1245/s10434-006-9154-1}, pmid = {17091330}, issn = {1068-9265}, support = {T32 GM008716/GM/NIGMS NIH HHS/United States ; K08 CA83753/CA/NCI NIH HHS/United States ; P50 CA58223/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*radiotherapy/*surgery ; Carcinoma, Ductal, Breast/pathology/*radiotherapy/*surgery ; *Dose Fractionation, Radiation ; Feasibility Studies ; Female ; Humans ; Intraoperative Period ; Mastectomy, Segmental ; Middle Aged ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: Accelerated partial breast irradiation (APBI) has gained widespread interest as a means of improving the convenience and availability of breast conserving radiotherapy. Intraoperative radiation therapy (IORT) is an APBI technique that delivers breast radiotherapy as a single dose at the time of partial mastectomy. We adapted the technique of Veronesi to deliver IORT prior to tumor excision to improve delivery to the region at risk and reduce the volume of normal tissue irradiated.

METHODS: Patients age >or=55 with ultrasonographically defined tumors
RESULTS: Twenty-three patients were enrolled in the study. Eighteen patients completed IORT with 10 patients having successful IORT no additional local therapy necessary. In five patients, the intraoperative radiation therapy served as the boost and in three patients unsuspected larger tumors or multicentric disease necessitated a mastectomy. The majority of patients had a good to excellent cosmetic result.

CONCLUSIONS: Single fraction in situ IORT prior to partial mastectomy is feasible for patients with small breast cancers in achieving a good to excellent cosmetic result. Based on this early preliminary data, we plan to expand our feasibility trial.}, } @article {pmid17090707, year = {2007}, author = {Sydnor, MK and Wilson, JD and Hijaz, TA and Massey, HD and Shaw de Paredes, ES}, title = {Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy.}, journal = {Radiology}, volume = {242}, number = {1}, pages = {58-62}, doi = {10.1148/radiol.2421031988}, pmid = {17090707}, issn = {0033-8419}, mesh = {Adult ; Aged ; Biopsy, Needle/statistics & numerical data ; Breast Neoplasms/diagnosis/*epidemiology/*pathology ; Carcinoma, Papillary/diagnosis/*epidemiology/*pathology ; False Negative Reactions ; Female ; Humans ; Mammography/statistics & numerical data ; Middle Aged ; Observer Variation ; Prevalence ; Reproducibility of Results ; Risk Assessment/*methods ; Risk Factors ; Sensitivity and Specificity ; Ultrasonography, Mammary/statistics & numerical data ; Virginia/epidemiology ; }, abstract = {PURPOSE: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy.

MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994-2003) revealed core biopsy diagnoses of benign papilloma (n=38), atypical papilloma (n=15), sclerotic papilloma (n=6), and micropapilloma (n=4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (>or=2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods.

RESULTS: In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n=1), sclerotic papilloma (n=1), micropapilloma (n=2), and atypical papilloma (n=10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n=2), ductal carcinoma in situ (n=7), papillary carcinoma (n=2), and invasive ductal carcinoma (n=3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P=.006). Lesion location, mammographic finding, core number, or needle type were not associated (P>.05) with underestimation of malignancy at excision.

CONCLUSION: Benign papilloma diagnosed at core biopsy is infrequently (3%) associated with malignancy; mammographic follow-up is reasonable. Because of the high association with malignancy (67%), diagnosis of atypical papilloma at core biopsy should prompt excision for definitive diagnosis.}, } @article {pmid17086115, year = {2006}, author = {Paillocher, N and Lacourtoisie, SA and Fondrinier, É and Catala, L and Morand, C and Boursier, J and Guerin, O and Descamps, P}, title = {[Infiltrating breast cancer in women younger than 25 years: 13 cases].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {35}, number = {11 Pt 1}, pages = {1618-1624}, doi = {10.1016/S0755-4982(06)74869-2}, pmid = {17086115}, issn = {0755-4982}, mesh = {Adult ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoma, Ductal/pathology/surgery ; Female ; Humans ; Neoplasm Invasiveness ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Analysis ; }, abstract = {OBJECTIVE: To study the prognosis of breast cancer in woman younger than 25 years and to compare it with that of other age groups to identify prognostic and histologic factors specific to this group.

METHOD: Retrospective study of all cases of infiltrating ductal carcinoma treated at our hospital from January 1977 through July 2005, examining clinical, histologic, and treatment variables as well as 5-year overall survival and 5-years disease-free survival rates.

RESULTS: The study included 13 women younger than 25 years at diagnosis. Their average age at diagnosis was 23.3 years (CI=1 year). Time from initial signs of disease until diagnosis averaged 6.6 months (CI=2.5). Clinically, the average tumor size was 28.78 mm (CI=6.06), with 46% classified as T1, 31% as T2 and 23% as T4d. We found 92.3% to be invasive ductal carcinoma, with 30% including an in-situ component; 53.8% were SBR grade 3 and 23% included axillary node invasion. Hormone receptors were present in 61.5% of tumors. During the follow-up period, we observed two deaths (with a 5-year overall survival rate, however, of 91%) and 6 recurrences (5-year disease-free survival: 66.5%).

CONCLUSION: Prognosis appears unfavorable among young women (younger than 40 years) with breast cancer. In our series, neither prognosis nor clinical or histologic characteristics differed in the subgroup of very young women (younger than 26 years).}, } @article {pmid17081394, year = {2006}, author = {Li, WM and Liu, W and Gao, C and Zhou, BG and Wang, Z and Zhang, RH and Kong, YH and Li, Y and Han, W and Gan, RT and Xue, HJ and Geng, JQ and Yang, SS and Shao, Q and Zhang, M}, title = {[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {34}, number = {8}, pages = {703-707}, pmid = {17081394}, issn = {0253-3758}, mesh = {Animals ; Animals, Genetically Modified ; Autoimmune Diseases/*immunology ; Bone Marrow Cells ; Cell Line ; Dendritic Cells/*immunology ; Genetic Therapy ; *Immune Tolerance ; Interleukin-10/*genetics/immunology ; Myocarditis/*immunology ; Rats ; Rats, Inbred Lew ; }, abstract = {OBJECTIVE: To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).

METHODS: EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.

RESULTS: EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.

CONCLUSION: Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.}, } @article {pmid17066230, year = {2007}, author = {Pezzi, CM and Patel-Parekh, L and Cole, K and Franko, J and Klimberg, VS and Bland, K}, title = {Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Data Base.}, journal = {Annals of surgical oncology}, volume = {14}, number = {1}, pages = {166-173}, doi = {10.1245/s10434-006-9124-7}, pmid = {17066230}, issn = {1068-9265}, mesh = {Breast Neoplasms/*pathology/therapy ; Carcinoma/*pathology/therapy ; Carcinoma, Ductal, Breast/*pathology/therapy ; Databases, Factual ; Humans ; Metaplasia ; United States ; }, abstract = {BACKGROUND: Metaplastic breast cancer (MBC) is characterized by various combinations of adenocarcinoma, mesenchymal, and other epithelial components. It was officially recognized as a distinct pathologic diagnosis in 2000. With few published reports, we hypothesized that MBC may have markedly different characteristics at presentation than typical infiltrating ductal carcinoma (IDC) and may be managed differently.

METHODS: Data from patients with MBC and IDC reported to the National Cancer Database from January 2001 through December 2003 were reviewed for year of diagnosis, patient age, race/ethnicity, tumor size, nodal status, American Joint Committee on Cancer (AJCC) stage, tumor grade, hormone receptor status, and initial treatment, and were analyzed statistically by the Pearson chi(2) test.

RESULTS: A total of 892 patients with MBC and 255,164 patients with IDC were identified. The group with MBC was older (mean age, 61.1 vs. 59.7 years; P = .001), had a significantly increased proportion of African American (14.1%, 126 of 892, vs. 10.2%, 25,900 of 255,164; odds ratio [OR], 1.455, P = .001) and Hispanic patients (5.5%, 49 of 892 vs. 3.9%, 9,947 of 255,164; OR, 1.817, P = .001), had fewer T1 tumors (29.5% vs. 65.2%), more N0 tumors (78.1% vs. 65.7%, OR, .5, P = .001), more poorly or undifferentiated tumors (67.8% vs. 38.8%), and fewer estrogen receptor-positive tumors (11.3% vs. 74.1%, OR, 22.4, P = .001) than the IDC group. Patients with MBC were treated with breast-conserving surgery less frequently than patients with IDC (38.5% vs. 55.8%, OR, 2.0, P = .001) because of the larger tumor size. Chemotherapy was used more often for patients with MBC (53.4% vs. 42.1%, OR, 1.6, P = .001) because of more advanced AJCC stage.

CONCLUSIONS: MBC is a rare tumor with different characteristics than IDC: it presents with larger tumor size, less nodal involvement, higher tumor grade, and hormone receptor negativity. Patients with MBC are treated more aggressively than IDC (more often with mastectomy and chemotherapy) because of a higher stage at presentation, but are being treated by the same principles as IDC. Follow-up will determine the long-term results of the current treatment.}, } @article {pmid17065184, year = {2007}, author = {Erdogan, D and Gullu, H and Caliskan, M and Ciftci, O and Baycan, S and Yildirir, A and Muderrisoglu, H}, title = {Nebivolol improves coronary flow reserve in patients with idiopathic dilated cardiomyopathy.}, journal = {Heart (British Cardiac Society)}, volume = {93}, number = {3}, pages = {319-324}, pmid = {17065184}, issn = {1468-201X}, mesh = {Benzopyrans/*administration & dosage ; Cardiomyopathy, Dilated/diagnostic imaging/*drug therapy/physiopathology ; Case-Control Studies ; Coronary Circulation/*drug effects ; Dose-Response Relationship, Drug ; Echocardiography ; Echocardiography, Doppler, Color ; Ethanolamines/*administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Nebivolol ; Treatment Outcome ; Vasodilator Agents/*administration & dosage ; }, abstract = {BACKGROUND: Impaired coronary flow reserve (CFR) is a significant predictor of poor prognosis in patients with idiopathic dilated cardiomyopathy (IDC). Nebivolol reduces mortality and morbidity in patients with heart failure and left ventricular dysfunction, including cases caused by IDC.

OBJECTIVE: To assess the effects of nebivolol on CFR in patients with IDC.

METHODS: CFR was measured in 21 clinically stable patients with IDC (mean (SD) ejection fraction 35.7 (6.2)) at baseline and after 1 month of treatment with nebivolol once daily. A control group of apparently healthy subjects who were matched for age and sex was used for comparison. Resting and hyperaemic coronary flows were measured using transthoracic second-harmonic Doppler echocardiography. None of the subjects had any systemic disease.

RESULTS: After 1 month of treatment, heart rate was reduced significantly (p<0.001). The blood pressure was decreased significantly (p<0.001). The left ventricular end-diastolic diameter and stroke volume were not changed significantly, but end-systolic diameter was decreased significantly (p<0.05). Resting rate-pressure product was lower after treatment with nebivolol, but dipyridamole-induced change was not influenced by the treatment. Nebivolol treatment reduced significantly coronary velocities at rest (p<0.02) and also caused a significant increase in coronary velocities after dipyridamole (p<0.02), leading to a greater CFR (2.02 (0.35) vs 2.61 (0.43), p<0.001). Nebivolol induced an absolute increase of 6% in the CFR in 17 of 21 patients (80.9%).

CONCLUSIONS: In patients with IDC, 1 month of treatment with nebivolol induces a marked increase in CFR.}, } @article {pmid17062971, year = {2006}, author = {Koike, A and Hoshimoto, M and Tajima, A and Nagayama, O and Yamaguchi, K and Goda, A and Yamashita, T and Sagara, K and Itoh, H and Aizawa, T}, title = {Critical level of cerebral oxygenation during exercise in patients with left ventricular dysfunction.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {70}, number = {11}, pages = {1457-1461}, doi = {10.1253/circj.70.1457}, pmid = {17062971}, issn = {1346-9843}, mesh = {Aged ; Blood Pressure/physiology ; Brain/*metabolism ; Cardiomyopathy, Dilated/physiopathology ; Cerebral Arteries/*physiology ; Consciousness/physiology ; Exercise/*physiology ; Exercise Test ; Female ; Humans ; Male ; Middle Aged ; Oxygen/*blood ; Regional Blood Flow/physiology ; Retrospective Studies ; Tachycardia, Ventricular/physiopathology ; Ventricular Dysfunction, Left/*metabolism/*physiopathology ; }, abstract = {BACKGROUND: In a recent study the indexes of cerebral oxygenation decreased during maximal exercise in nearly half of all patients with left ventricular dysfunction. Whether these levels decrease severely enough to influence mental status or level of consciousness was evaluated in the present study.

METHODS AND RESULTS: Forty-two patients with idiopathic dilated cardiomyopathy (IDC) and 29 healthy subjects underwent a symptom-limited maximal exercise test. The cerebral oxyhemoglobin (O(2)Hb) and tissue oxygenation index (TOI) were continuously monitored using near-infrared spectroscopy. The changes in O(2)Hb and TOI were also measured in 7 subjects: 2 who experienced episodes of reduced consciousness caused by sudden decreases in blood pressure during exercise recovery and 5 who exhibited sustained ventricular tachycardia during an electrophysiological study. The change in cerebral O(2)Hb during exercise in patients with IDC averaged 0.38+/-3.39 micromol/L, significantly lower than in the normal subjects (4.30+/-4.47 micromol/L, p<0.0001). The cerebral O(2)Hb decreased during exercise in 18 of 42 patients with IDC. The change in cerebral TOI in the IDC patients during exercise was significantly less than that in the normal subjects (-2.0+/-4.7 vs 2.1+/-5.8%, p=0.002). The mean decreases in cerebral O(2)Hb and TOI were -5.34 micromol/L and -9.7%, respectively, in the patients with reduced consciousness during exercise recovery, and -2.52 micromol/L and -16.5%, respectively, in those with ventricular tachycardia.

CONCLUSION: The indexes of cerebral oxygenation may drop severely enough during maximal exercise in some patients with severe IDC that consciousness is affected.}, } @article {pmid17061934, year = {2006}, author = {Hoyer, D and Frank, B and Götze, C and Schmidt, H and Baranowski, R and Zebrowski, JJ and Vallverdú, M and Caminal, P and Bayés De Luna, A and Falkenhahn, K and Bär, KJ and Stein, PK}, title = {Complex autonomic dysfunction in cardiovascular, intensive care, and schizophrenic patients assessed by autonomic information flow.}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {51}, number = {4}, pages = {182-185}, doi = {10.1515/BMT.2006.032}, pmid = {17061934}, issn = {0013-5585}, mesh = {Autonomic Nervous System/*physiopathology ; Autonomic Nervous System Diseases/complications/diagnosis/*physiopathology ; *Biological Clocks ; Critical Care ; Diagnosis, Computer-Assisted/methods ; Electrocardiography/methods ; Heart Failure/complications/diagnosis/*physiopathology ; *Heart Rate ; Humans ; Information Storage and Retrieval/methods ; Male ; Multiple Organ Failure/complications/diagnosis/*physiopathology ; Schizophrenia/complications/diagnosis/*physiopathology ; }, abstract = {BACKGROUND: The cardiovascular control system is mediated by mechanisms acting at different time scales, such as heart period, vagal, sympathetic, and other slower controllers. Since these elements are interrelated in a complex manner, classical control theory fails and information-based description, based on autonomic information flow (AIF) functions, is appropriate. We investigated the hypothesis that AIF functions of typical time scales specifically characterize autonomic dysfunction and prognosis.

MATERIALS AND METHODS: Holter recordings of patients with multiple organ dysfunction syndrome (MODS) (26 survivors, 10 non-survivors), heart failure (13 low risk, 13 high risk of cardiac arrest), idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk), after abdominal aorta surgery (AAS) [32 with length of stay in hospital (LOS) >7 days; 62 with LOS < or =7 days] or with schizophrenia (n=20) were assessed and compared to 20 control subjects.

RESULTS: We found different AIF time scales discriminating risk. AIF measures of heart beat period had predominant prognostic value in heart failure patients, those of vagal communication in MODS and IDC, and those of long-term communication after AAS. Schizophrenic patients were discriminated from controls by vagally mediated communication.

CONCLUSION: Different time scales of AIF represent specific pathophysiological aspects of altered complex autonomic control (communication) and consequently have predictive implications.}, } @article {pmid17061042, year = {2007}, author = {Wenzel, C and Bartsch, R and Hussian, D and Pluschnig, U and Altorjai, G and Zielinski, CC and Lang, A and Haid, A and Jakesz, R and Gnant, M and Steger, GG}, title = {Invasive ductal carcinoma and invasive lobular carcinoma of breast differ in response following neoadjuvant therapy with epidoxorubicin and docetaxel + G-CSF.}, journal = {Breast cancer research and treatment}, volume = {104}, number = {1}, pages = {109-114}, doi = {10.1007/s10549-006-9397-3}, pmid = {17061042}, issn = {0167-6806}, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Austria/epidemiology ; Breast Neoplasms/*drug therapy/mortality/pathology ; Carcinoma, Ductal, Breast/*drug therapy/mortality/pathology ; Carcinoma, Lobular/*drug therapy/mortality/pathology ; Disease-Free Survival ; Docetaxel ; Doxorubicin/*administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor/administration & dosage ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Survival Analysis ; Taxoids/*administration & dosage ; Treatment Outcome ; }, abstract = {PURPOSE: Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes results in high response rates, allowing breast conserving surgery (BCS) in patients primarily not suitable for this procedure. Pathological responses are important prognostic parameters for progression free and overall survival. We questioned the impact of histologic type invasive ductal carcinoma (IDC) versus invasive lobular carcinoma (ILC) on response to primary chemotherapy.

PATIENTS AND METHODS: 161 patients with breast cancer received preoperative chemotherapy consisted of epidoxorubicin 75 mg/m(2) and docetaxel 75 mg/m(2) administered in combination with granulocyte-colony stimulating factor (G-CSF) on days 3-10 (ED + G). Pathological complete response (pCR), biological markers and type of surgery as well as progression free and overall survival were compared between IDC and ILC.

RESULTS: Out of 161 patients, 124 patients presented with IDC and 37 with ILC. Patients with ILC were less likely to have a pCR (3% vs. 20%, P < 0.009) and breast conserving surgeries (51% vs. 79%, P < 0.001). Patients with ILC tended to have oestrogen receptor positive tumors (86% vs. 52%, P < 0.0001), HER 2 negative tumors (69% vs. 84%), and lower nuclear grade (nuclear grade 3, 16% vs. 46%, P < 0.001). Patients with ILC tended to have longer time to progression (TTP) (42 months vs. 26 months) and overall survival (69 months vs. 65 months).

CONCLUSIONS: Our results indicate that patients with ILC achieved a lower pCR rate and ineligibility for BCS to preoperative chemotherapy, but this did not result in a survival disadvantage. Because of these results new strategies to achieve a pCR are warranted.}, } @article {pmid17060025, year = {2006}, author = {Liu, W and Li, WM and Yang, SS and Gao, C and Li, SJ and Li, Y and Kong, YH and Gan, RT}, title = {Association of HLA class II DRB1, DPA1 and DPB1 polymorphism with genetic susceptibility to idiopathic dilated cardiomyopathy in Chinese Han nationality.}, journal = {Autoimmunity}, volume = {39}, number = {6}, pages = {461-467}, doi = {10.1080/08916930600893709}, pmid = {17060025}, issn = {0891-6934}, mesh = {Alleles ; Asian People ; Cardiomyopathy, Dilated/*genetics/immunology ; Case-Control Studies ; China ; Female ; *Genetic Predisposition to Disease ; Genotype ; HLA-DP Antigens/*genetics/immunology ; HLA-DR Antigens/*genetics/immunology ; Humans ; Male ; *Polymorphism, Genetic ; }, abstract = {Although the aetiology of idiopathic dilated cardiomyopathy (IDC) remains unclear, many immunological abnormalities involving changes in cell-mediated and humoral immunity may be associated with cardiac impairment in IDC. Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of IDC and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, which are highly polymorphic, play an important role in the activating of immune responses and thus control the predisposition for or protection from IDC. This study explores the possible contribution of HLA-DRB and DP polymorphisms to IDC susceptibility. DNA genotyping for HLA-DRB1, DPA1 and DPB1 was performed using polymerase chain reaction-sequencing based typing (PCR-SBT) method in 198 IDC patients and 136 random selected healthy Han ethnic individuals living in Northern China. IDC patients were, sub-grouped into asymptomatics (subgroup A), with arrhythmia (subgroup B) and with overt congestive heart failure (subgroup C) according to the clinical manifestations and electrocardiogram or echocardiographic characteristics. ADP/ATP autoantibody was detected in IDC group by immunoblot analysis. The results revealed that HLA-DR15, -DPB*0601 frequencies were significantly elevated in IDC group compared with normal control. The DPB1*0601 allele in homozygous form or in combination with allele DPB1*2301 or *3901, was found present more often in IDC patients. The predominance of HLA-DR4 allele was observed in subgroup B after stratification. However, the frequency of DPB1*0101 allele increased in the control than in the IDC group. The frequency of HLA-DPB1*0601 allele was significantly higher in IDC patients with positive autoantibody against ADP/ATP carrier of myocardial mitochondria in contrast to those with negative autoantibody. We conclude that HLA-DR4, -DR15, -DPB1*0601 alleles confers susceptibility to, while DPB1*0101 allele confers protection from IDC among individuals of northern Chinese Han nationality. The glutamate at position 69 in the second exon of DPB1*0601, as a key residue for special conformation of HLA-DP, may confer predisposition to IDC. HLA-DR and -DP alleles polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.}, } @article {pmid17059779, year = {2006}, author = {Lian, ZQ and Yang, MT and Hou, JH and Luo, RZ and Wang, X and Tang, J}, title = {[Expression and clinical significance of adhesive molecule CD44v6 in breast invasive ductal carcinoma].}, journal = {Ai zheng = Aizheng = Chinese journal of cancer}, volume = {25}, number = {10}, pages = {1291-1295}, pmid = {17059779}, mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Glycoproteins/*metabolism ; Humans ; Hyaluronan Receptors/*metabolism ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Receptors, Estrogen/metabolism ; Survival Rate ; }, abstract = {BACKGROUND & OBJECTIVE: Many researches suggest that CD44v6 is associated with the occurrence, invasion, and metastasis of breast cancer. However the reports about the relationship between CD44v6 expression and the prognosis of breast cancer are conflicting. This study was to investigate the expression of CD44v6 and its correlation to clinicopathologic characteristics and prognosis of breast cancer.

METHODS: CD44v6 expression in 84 specimens of breast cancer and 20 specimens of para-tumor breast tissues was detected by SP immunohistochemistry. COX proportional hazards model was used to analyze the prognosis.

RESULTS: The positive rate of CD44v6 in the epithelial cells of breast cancer was significantly higher than that in para-tumor breast tissues (78.6% vs. 5.0%, P<0.05). The expression of CD44v6 was closely correlated to TNM stage, tumor size, and lymph node metastasis (P<0.05). The median follow-up period was 60 months. The overall survival rate was significantly higher in CD44v6-negative group than in CD44v6-positive group (P<0.05). The survival curve had a tendency to decline with the stronger expression of CD44v6. Cox model revealed that ER, TNM stage, and CD44v6 were independent prognostic factors of breast cancer.

CONCLUSIONS: CD44v6 is highly expressed in breast cancer, and positively correlated to TNM stage, tumor size, and lymph node metastasis. CD44v6 is an independent prognostic factor of breast cancer.}, } @article {pmid17058095, year = {2006}, author = {Burga, AM and Fadare, O and Lininger, RA and Tavassoli, FA}, title = {Invasive carcinomas of the male breast: a morphologic study of the distribution of histologic subtypes and metastatic patterns in 778 cases.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {449}, number = {5}, pages = {507-512}, pmid = {17058095}, issn = {0945-6317}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/classification/*pathology ; Child ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; }, abstract = {The current investigation was conducted to evaluate the proportional distribution of the various histologic subtypes (including newly recognized variants) of male breast carcinomas, to determine whether any histologic subtypes occur with a frequency that is markedly discordant with the expected frequencies from published data on parallel female breast tumors. We also aimed to document the distribution of malignancies metastatic to the breast. Seven hundred fifty-nine archived cases of primary invasive carcinoma involving the male breast were retrieved and sub-categorized into histologic subtypes according to contemporary criteria. Six hundred forty-three (84.7%) tumors were pure infiltrating ductal carcinoma (IDC) not otherwise specified. The most common of the remainder included papillary carcinoma with invasion in the form of IDC (n = 34), mixed IDC and mucinous carcinoma (n = 26), and pure mucinous carcinoma (n = 21). In 19 cases, metastases from other sites involved the breast, most commonly (58%) cutaneous melanoma. Invasive carcinoma of the male breast appears to display a morphologic spectrum and distribution of histologic subtypes that is comparable to those of the female breast, with some expected variation. Compared with published experience on their female counterparts, there is a two-fold increase in the frequency of invasive papillary carcinoma in the male breast. Finally, the most common tumor metastatic to the male breast in this series was cutaneous melanoma.}, } @article {pmid17056095, year = {2007}, author = {Yamauchi, C and Hasebe, T and Iwasaki, M and Imoto, S and Wada, N and Fukayama, M and Ochiai, A}, title = {Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance.}, journal = {Human pathology}, volume = {38}, number = {2}, pages = {247-259}, doi = {10.1016/j.humpath.2006.07.017}, pmid = {17056095}, issn = {0046-8177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/analysis ; Antibodies, Monoclonal, Murine-Derived ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Histocytochemistry ; Humans ; Immunohistochemistry ; Lymphatic Metastasis/*diagnosis ; Lymphatic Vessels/metabolism/*pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Predictive Value of Tests ; Prognosis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; }, abstract = {Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40-positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.}, } @article {pmid17048437, year = {2006}, author = {Wiratkapun, C and Lertsithichai, P and Wibulpholprasert, B}, title = {Positive predictive value of breast cancer in the lesions categorized as BI-RADS category 5.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {89}, number = {8}, pages = {1253-1259}, pmid = {17048437}, issn = {0125-2208}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Female ; Humans ; *Mammography ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; *Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: To determine positive predictive value (PPV) of the breast imaging reporting and data systems (BI-RADS) category 5 mammogram and ultrasound (US) in the diagnosis of breast cancer in the study center and correlation between clinical, mammographic and US findings, and breast cancer.

MATERIAL AND METHOD: Four hundred and ninety seven patients with BI-RADS category 5 who underwent mammograms and US at the Breast diagnostic center, Ramathibodi Hospital from January, 1, 2002 to December 31, 2004 were enrolled into the present study. Selected clinical information, mammographic and US findings, and histopathological diagnosis were retrospectively reviewed.

RESULTS: Breast cancer was found in 467 of 497 patients, giving a PPV of 94%. Invasive ductal carcinoma was the most common malignancy (89.5%). Fibrocystic change was the most common benign pathology found in the remaining patients. Discrete mass was the most frequently encountered lesion detected on mammography and US, followed by mass containing calcifications. Patients with advanced age, having a clinically palpable breast mass, with mammographic and US evidence of mass containing calcifications showed significant statistical association with breast cancer.

CONCLUSION: PPV of BI-RADS category 5 lesions in the present study was comparable to other published studies. Although the probability of malignancy was very high, a small number of patients had benign pathologies. Preoperative histopathologic diagnosis is necessary before definitive treatment.}, } @article {pmid17047060, year = {2006}, author = {Chen, D and Kennedy, A and Wang, JY and Zeng, W and Zhao, Q and Pearl, M and Zhang, M and Suo, Z and Nesland, JM and Qiao, Y and Ng, AK and Hirashima, N and Yamane, T and Mori, Y and Mitsumata, M and Ghersi, G and Chen, WT}, title = {Activation of EDTA-resistant gelatinases in malignant human tumors.}, journal = {Cancer research}, volume = {66}, number = {20}, pages = {9977-9985}, pmid = {17047060}, issn = {0008-5472}, support = {R01 CA039077/CA/NCI NIH HHS/United States ; R01EB002065/EB/NIBIB NIH HHS/United States ; R01 EB002065/EB/NIBIB NIH HHS/United States ; M01 RR010710/RR/NCRR NIH HHS/United States ; M01RR10710/RR/NCRR NIH HHS/United States ; R01CA0039077/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Edetic Acid/*pharmacology ; Endopeptidases ; Enzyme Activation ; Gelatinases/biosynthesis/genetics/isolation & purification/*metabolism ; Haplorhini ; Humans ; Membrane Proteins/biosynthesis/genetics/isolation & purification/*metabolism ; Models, Molecular ; Neoplasms/*enzymology/pathology ; Protein Conformation ; Recombinant Proteins/genetics/isolation & purification/metabolism ; Serine Endopeptidases/biosynthesis/genetics/isolation & purification/*metabolism ; }, abstract = {Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion.}, } @article {pmid17045008, year = {2006}, author = {Zhao, WH and Xu, BH and Li, Q and Zhang, P and Sun, Y}, title = {[Clinical features and prognosis in breast cancer patients over 70 years of age].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {28}, number = {5}, pages = {385-388}, pmid = {17045008}, issn = {0253-3766}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/complications/pathology/*surgery ; Carcinoma, Ductal, Breast/complications/pathology/*surgery ; Coronary Disease/complications ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy/*methods ; Neoplastic Cells, Circulating/pathology ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: To investigate the clinical characteristics and prognostic factors in breast cancer patients over 70 years of age.

METHODS: From 1980 to 2003, 280 female breast cancer patients over 70 years old were treated and the data were retrospectively reviewed. The clinical features including age, comorbidity, initial symptom, tumor size and location, pathological type, lymph node status, hormonal receptor status, treatment approaches and overall survival were analyzed.

RESULTS: These 280 patients accounted for 2.9% of all breast cancer patients registered in our institution during the same period. Presentation of breast lump as initial symptom accounted for 92.5% of the patients. The median time from the presentation of initial symptom to initial diagnosis was 4 months. Major pathological type was invasive ductal carcinoma (74.3%). Estrogen or progesterone receptor was found to be positive in 72.9% by immunohistochemical staining. 165 patients (58.9%) had comorbidity such as coronary heart disease, hypertension, diabetes, etc. 256 patients underwent surgery consisting of 162 modified mastectomies, 46 mastectomies, 38 lumpectomies, 7 lumpectomies plus lymph node dissection, 2 lymph node resection and 1 with unavailable surgery record. The cumulative 5- and 10-year overall survival was 69.9% and 40.6%, respectively. Factors affecting the prognosis were tumor size, lymph node status, pathological stage, vascular invasion and endocrine therapy by univariate analysis. The lymph node status and vascular invasion were found to be two independent prognostic factors affecting significantly the prognosis by multivariate analysis.

CONCLUSION: Female breast cancer patients over 70 years of age exhibit distinctive clinical and pathological characteristics. Surgery and endocrine therapy are important to achieve good clinical outcome. Lymph node status and vascular invasion are two independent prognostic factors.}, } @article {pmid17044772, year = {2006}, author = {Eason, RR and Till, SR and Frank, JA and Badger, TM and Korourian, S and Simmen, FA and Simmen, RC}, title = {Tumor-protective and tumor-promoting actions of dietary whey proteins in an N-methyl-N-nitrosourea model of rat mammary carcinogenesis.}, journal = {Nutrition and cancer}, volume = {55}, number = {2}, pages = {171-177}, doi = {10.1207/s15327914nc5502_8}, pmid = {17044772}, issn = {0163-5581}, mesh = {9,10-Dimethyl-1,2-benzanthracene/toxicity ; Animals ; Anticarcinogenic Agents/administration & dosage/*pharmacology ; Caseins/administration & dosage/pharmacology ; Cell Differentiation/drug effects ; Disease Models, Animal ; Female ; Genetic Predisposition to Disease ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/*epidemiology/pathology/*prevention & control ; Milk Proteins/administration & dosage/*pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Proliferating Cell Nuclear Antigen/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Whey Proteins ; }, abstract = {The mammary tumor-protective effects of dietary factors are considered to be mediated by multiple signaling pathways, consistent with the heterogeneous nature of the disease and the distinct genetic profiles of tumors arising from diverse mammary cell populations. In a 7,12-dimethylbenz(a)anthracene-induced model of carcinogenesis, we showed previously that female Sprague-Dawley rats exposed to AIN-93G diet containing whey protein hydrolysate (WPH) beginning at gestation Day 4 had reduced tumor incidence than those exposed to diet containing casein (CAS), due partly to increased mammary differentiation and reduced activity of phase I metabolic enzymes. Here, we evaluated the tumor-protective effects of these same dietary proteins to the direct-acting carcinogen N-methyl-N-nitrosourea (NMU). We found that lifetime exposure to WPH, relative to CAS, decreased mammary tumor incidence and prolonged the appearance of tumors in NMU-treated female rats, with no corresponding effects on tumor multiplicity. At 115 days post-NMU, histologically normal mammary glands from WPH-fed tumor-bearing rats had increased gene expression for the tumor suppressor BRCA1 and the differentiation marker kappa-casein than those of CAS-fed tumor-bearing rats. Tumor-bearing rats from the WPH group had more advanced tumors, with a greater incidence of invasive ductal carcinoma than ductal carcinoma in situ and higher serum C-peptide levels than corresponding rats fed CAS. WPH-fed tumor-bearing rats were also heavier after NMU administration than CAS tumor-bearing rats, although no correlation was noted between body weight and C-peptide levels for either diet group. Results demonstrate the context-dependent tumor-protective and tumor-promoting effects of WPH; provide support for distinct signaling pathways underlying dietary effects on development of mammary carcinoma; and raise provocative questions on the role of diet in altering the prognosis of existing breast tumors.}, } @article {pmid17042978, year = {2006}, author = {Li, WM and Liu, W and Gao, C and Zhou, BG and Yang, SS and Wang, Z and Zhang, RH and Gan, RT and Kong, YH and Li, Y}, title = {Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats.}, journal = {Chinese medical journal}, volume = {119}, number = {19}, pages = {1646-1652}, pmid = {17042978}, issn = {0366-6999}, mesh = {Animals ; Autoimmune Diseases/*immunology ; Dendritic Cells/*physiology ; *Immune Tolerance ; Interleukin-10/*genetics ; Lymphocyte Activation ; Male ; Myocarditis/*immunology ; Myosins/*immunology ; NF-kappa B/physiology ; Rats ; Rats, Inbred Lew ; Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.

METHODS: EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.

RESULTS: BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.

CONCLUSIONS: IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.}, } @article {pmid17041796, year = {2006}, author = {Hikino, H and Yasui, K and Ozaki, N and Nagaoka, S}, title = {Significance of preoperative lymphoscintigraphy and thin-slice computed tomography on sentinel node assessment: metastatic sentinel node in a lateral paramammary lesion out of axillary nodes from breast cancer.}, journal = {Radiation medicine}, volume = {24}, number = {8}, pages = {583-586}, pmid = {17041796}, issn = {0288-2043}, mesh = {Adult ; Axilla ; Breast Neoplasms/diagnosis/*pathology/surgery ; Carcinoma, Ductal, Breast/diagnosis/*secondary/surgery ; Female ; Humans ; *Lymph Node Excision ; Lymph Nodes/*diagnostic imaging/pathology/surgery ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mammography ; Neoplasm Staging ; Radionuclide Imaging ; Sentinel Lymph Node Biopsy ; *Tomography, X-Ray Computed ; Ultrasonography, Interventional ; }, abstract = {Sentinel node status was evaluated using preoperative lymphoscintigraphy in a 43-year-old woman who presented with an invasive ductal carcinoma in the lower outer quadrant of the right breast. Two strong hot nodules were visualized in the affected axillary basin on an early image, and a faint accumulation of radioactive tracer was lying between the cancer in the right lower outer quadrant and the axillary hot nodules on the lymphoscintigram taken at 90 min. The faint accumulation was considered to represent a small paramammary node on thin-slice computed tomography (CT) and was confirmed by node biopsy to be a sentinel node grossly involved with tumor cells. Immediate axillary dissection and adjuvant chemotherapy was subsequently performed. Careful evaluation using lymphoscintigraphy and thin-slice CT may be associated with increased localization of true sentinel nodes.}, } @article {pmid17025093, year = {2006}, author = {Ogata, S and Kadokawa, J and Tagaya, H}, title = {pH sensitive organic-inorganic layered nanomaterials by self-assembly of indigocarmine between the inorganic layers.}, journal = {Journal of nanoscience and nanotechnology}, volume = {6}, number = {6}, pages = {1826-1829}, doi = {10.1166/jnn.2006.203}, pmid = {17025093}, issn = {1533-4880}, mesh = {Hydrogen-Ion Concentration ; Indigo Carmine/*chemistry ; Intercalating Agents ; Nanostructures/*chemistry ; Nanotechnology/methods ; Spectrophotometry, Infrared ; Water/chemistry ; X-Ray Diffraction ; }, abstract = {New pH sensitive organic-inorganic intercalation compounds having different interlayer spacing were prepared. Zn-Al layered double hydroxide (LDH) is an anion exchangeable inorganic layered compound whose interlayer spacing is 0.76 nm. In the reactions of indigocarmine (IDC) with the calcined Zn-Al LDH at pH = 7 (LDH-IDC7), interlayer spacing increased to 2.25 nm. The interlayer spacing of LDH-IDC7 decreased to 1.89 nm by the treatment in basic solution. In the reaction of IDC with the calcined Zn-Al LDH at pH = 10 (LDH-IDC10), interlayer spacing of the intercalation compounds was 1.89 nm. The interlayer spacing of these intercalation compounds was changed reversibly by the treatments in acidic or basic solution.}, } @article {pmid17019712, year = {2006}, author = {Schneider, J and Ruschhaupt, M and Buness, A and Asslaber, M and Regitnig, P and Zatloukal, K and Schippinger, W and Ploner, F and Poustka, A and Sültmann, H}, title = {Identification and meta-analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer.}, journal = {International journal of cancer}, volume = {119}, number = {12}, pages = {2974-2979}, doi = {10.1002/ijc.22234}, pmid = {17019712}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Cation Transport Proteins/genetics ; Cluster Analysis ; Female ; GATA3 Transcription Factor/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*genetics ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Middle Aged ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis/methods ; Receptors, Estrogen/genetics/*metabolism ; Reproducibility of Results ; }, abstract = {In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta-analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone.}, } @article {pmid17007744, year = {2006}, author = {Lee, HY and Shin, EH and Bae, YS}, title = {Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis.}, journal = {Acta pharmacologica Sinica}, volume = {27}, number = {10}, pages = {1359-1366}, doi = {10.1111/j.1745-7254.2006.00426.x}, pmid = {17007744}, issn = {1671-4083}, mesh = {Chemotaxis/*drug effects ; Dendritic Cells/cytology/drug effects/*metabolism ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mitogen-Activated Protein Kinases/metabolism ; Monocytes/cytology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Phosphorylcholine/*analogs & derivatives/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Receptors, Lysosphingolipid/antagonists & inhibitors ; Sphingosine/*analogs & derivatives/pharmacology ; }, abstract = {AIM: To investigate the effects of sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis.

METHODS: Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction.

RESULTS: We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphingosine-1-phosphate (S1P) receptors, we checked the effect of an S1P receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis.

CONCLUSION: The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from S1P receptors, is involved in SPC-induced chemotaxis.}, } @article {pmid17000674, year = {2006}, author = {Ohuchida, K and Mizumoto, K and Egami, T and Yamaguchi, H and Fujii, K and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {S100P is an early developmental marker of pancreatic carcinogenesis.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {12}, number = {18}, pages = {5411-5416}, doi = {10.1158/1078-0432.CCR-06-0298}, pmid = {17000674}, issn = {1078-0432}, mesh = {Adenocarcinoma, Mucinous/metabolism ; Biomarkers/*metabolism ; Calcium-Binding Proteins/*metabolism ; Carcinoma/*metabolism ; Carcinoma, Pancreatic Ductal/metabolism ; Carcinoma, Papillary/metabolism ; Cell Culture Techniques ; Cell Line, Tumor ; Disease Progression ; Fibroblasts/metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Pancreas/metabolism ; Pancreatic Juice/metabolism ; Pancreatic Neoplasms/*metabolism/pathology ; RNA, Messenger/metabolism ; }, abstract = {PURPOSE: Our goal was to clarify the involvement and clinical significance of S100P in pancreatic carcinogenesis.

EXPERIMENTAL DESIGN: We examined S100P expression in 45 bulk pancreatic tissues; in microdissected cells, including invasive ductal carcinoma (IDC) cells (20 sections), pancreatic intraepithelial neoplasia (PanIN) cells (12 sections), intraductal papillary mucinous neoplasm (IPMN) cells (19 sections), and normal epithelial cells (11 sections); and in pancreatic juice samples from 99 patients with pancreatic diseases (32 cancer, 35 IPMN, and 32 chronic pancreatitis samples). We used quantitative real-time reverse transcription-PCR with gene-specific priming to measure S100P in these various types of samples.

RESULTS: In bulk tissue analyses, pancreatic cancer and IPMN expressed significantly higher levels of S100P than did nonneoplastic pancreas (P<0.017 and P=0.0013, respectively). Microdissection analyses revealed that IPMN expressed significantly higher levels of S100P than did IDC (P<0.0001) and PanIN (P=0.0031), although S100P expression did not differ between IDC and PanIN (P=0.077). In pancreatic juice analyses, cancer and IPMN juice expressed significantly higher levels of S100P than did pancreatitis juice (both P<0.0001). Receiver operating characteristic curve analyses revealed that measurement of S100P in pancreatic juice was useful for discriminating neoplastic disease from chronic pancreatitis (area under the curve=0.837; 95% confidence interval, 0.749-0.903).

CONCLUSION: S100P may be an early developmental marker of pancreatic carcinogenesis, and measurement of S100P in pancreatic juice may be useful for early detection of pancreatic cancer or screening of early pancreatic carcinogenesis.}, } @article {pmid16999196, year = {2006}, author = {Ekanem, VJ and Aligbe, JU}, title = {Histopathological types of breast cancer in Nigerian women: a 12-year review (1993-2004).}, journal = {African journal of reproductive health}, volume = {10}, number = {1}, pages = {71-75}, pmid = {16999196}, issn = {1118-4841}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/epidemiology/*pathology ; Carcinoma, Ductal, Breast/diagnosis/epidemiology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/*pathology ; Carcinoma, Papillary/diagnosis/epidemiology/*pathology ; Female ; Humans ; Male ; Middle Aged ; Nigeria/epidemiology ; }, abstract = {To determine the commonest histological types of breast cancer in Nigerian women in Edo State and the mean age at diagnosis, we reviewed the histological slides of breast cancer received in the pathology department of University of Benin Teaching Hospital over a twelve-year period (January 1993-December 2004). The clinical data was obtained from the original request form and case notes where necessary. The mean age of the patients was 45.7 (SD= 13.4, SEM = 0.7). Invasive ductal carcinoma (not otherwise specified) constituted the majority of breast cancer accounting for 75.5% while papillary carcinoma was the least common (2.7%). Ductal carcinoma in situ accounted for 6.6%. Breast cancer occur more on the left (53.3%) than the right (45.7%). Bilateral breast cancer was found in only 0.8% of the cases. The frequency of invasive breast cancer is still very high among Nigerian women. Late presentation possibly due to ignorance, alternative medicine and fear of surgery may account for this high prevalence.}, } @article {pmid16998326, year = {2006}, author = {Alam, M and Kiely, C and Shah, SH and Lawlor, C and O'Donnell, M}, title = {Mastectomy scar histopathology of limited clinical value.}, journal = {Annals of plastic surgery}, volume = {57}, number = {4}, pages = {374-375}, doi = {10.1097/01.sap.0000237565.39876.f9}, pmid = {16998326}, issn = {0148-7043}, mesh = {Breast Neoplasms/*pathology/surgery ; Cicatrix/*pathology ; Female ; Humans ; Mammaplasty/methods ; *Mastectomy ; Neoplasm Staging ; Retrospective Studies ; Surgical Flaps ; Time Factors ; }, abstract = {This study assesses whether the routine submission of mastectomy scars for histologic examination at the time of delayed breast reconstruction is useful. A retrospective review was performed of all delayed breast reconstructions for breast cancer performed by a single surgeon over a 5-year period from January 2000 to December 2004. One hundred eighty-eight patients underwent delayed breast reconstruction during this period, and of these, 133 scars (1 patient had bilateral scars excised) were submitted for histology where the reconstruction was performed by either transversus rectus abdominus muscle flap (TRAM) or latissimus dorsi myocutaneous flap (LDF) +/- implant. Fifty-six patients had reconstruction performed by tissue expander through the inframammary crease where the original mastectomy scar was not excised and were excluded from the study. One mastectomy scar specimen showed a 2-mm suspicious area of invasive ductal carcinoma consistent with same histopathology at the time of mastectomy. This study corroborates evidence that it is questionable whether routine histopathology of mastectomy scar at the time of delayed breast reconstruction should not be a standard practice.}, } @article {pmid16997859, year = {2007}, author = {Semino, C and Ceccarelli, J and Lotti, LV and Torrisi, MR and Angelini, G and Rubartelli, A}, title = {The maturation potential of NK cell clones toward autologous dendritic cells correlates with HMGB1 secretion.}, journal = {Journal of leukocyte biology}, volume = {81}, number = {1}, pages = {92-99}, doi = {10.1189/jlb.0306172}, pmid = {16997859}, issn = {0741-5400}, mesh = {Antigens, CD/physiology ; Cell Differentiation ; Cells, Cultured ; *Chemotaxis ; Clone Cells/physiology ; Dendritic Cells/*physiology ; GPI-Linked Proteins ; HMGB1 Protein/*metabolism ; Humans ; Killer Cells, Natural/metabolism/*physiology ; Membrane Glycoproteins/metabolism ; Natural Cytotoxicity Triggering Receptor 3 ; Phospholipases A/metabolism ; Receptors, IgG/physiology ; Receptors, Immunologic/metabolism ; }, abstract = {Interaction of NK cells with autologous immature dendritic cells (iDCs) results in reciprocal activation. We have previously reported that NK cells trigger iDC to polarize and secrete IL-18; in turn, DC-activated NK cells secrete the nuclear protein/proinflammatory cytokine high mobility group box protein 1 (HMGB1), which induces DC maturation and prevents DC from lysis. However, activated NK cells can also kill iDC. To investigate whether effector and maturative properties may coexist or segregate in different NK subsets, human NK cell clones were generated and analyzed for their effects on iDC. We found that the ability of different NK cell clones to induce iDC maturation is unlinked to their phenotypic and cytolytic features but correlates with the relocation of HMGB1 from nucleus to cytoplasm. "Maturative" NK cell clones secrete HMGB1 spontaneously. It is interesting that secretion is strongly enhanced by engagement of the surface molecule NKp30 but only slightly induced by triggering of the activating NK receptor CD16. However, culturing freshly isolated NK cells for 1 week with low doses of anti-CD16 triggers the relocation of HMGB1 from nucleus to cytoplasm and its spontaneous secretion, resulting in a stronger maturation potential of the NK cells. Together, our data indicate that NK cells comprise functionally different subsets, endowed with different capacities to secrete HMGB1 and to induce maturation of autologous iDC. Nonetheless, maturation properties can be modulated by different stimuli. This suggests that depending on the environmental stimuli, NK/iDC interaction can lead to different outcomes, thus influencing immune response.}, } @article {pmid16997856, year = {2006}, author = {Joshi, PS and Liu, JQ and Wang, Y and Chang, X and Richards, J and Assarsson, E and Shi, FD and Ljunggren, HG and Bai, XF}, title = {Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent and perforin-dependent mechanisms.}, journal = {Journal of leukocyte biology}, volume = {80}, number = {6}, pages = {1345-1353}, doi = {10.1189/jlb.0506305}, pmid = {16997856}, issn = {0741-5400}, support = {R21AI166T8/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Cytotoxicity, Immunologic ; Dendritic Cells ; Interferon-gamma/*immunology ; Killer Cells, Lymphokine-Activated/*immunology ; Lymphocyte Activation/*immunology ; Membrane Glycoproteins/*immunology ; Mice ; Neoplasms/immunology ; Perforin ; Pore Forming Cytotoxic Proteins/*immunology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; }, abstract = {Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven anticancer activity in vitro and in vivo. However, their functional properties with the exception of their cancer cell-killing activity are largely unclear. Here, we show that CIK T cells recognize dendritic cells (DC), and although mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are killed selectively by them. Moreover, CIK T cell activation by mDC and their destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to iDC is perforin-dependent. Our data have revealed an important regulatory role of CIK cells.}, } @article {pmid16986389, year = {2006}, author = {Voth, M and Budway, R and Keleher, A and Caushaj, PF}, title = {Local recurrence of breast cancer after MammoSite brachytherapy.}, journal = {The American surgeon}, volume = {72}, number = {9}, pages = {798-800; discussion 800-1}, pmid = {16986389}, issn = {0003-1348}, mesh = {Biopsy, Fine-Needle ; *Brachytherapy/methods ; Breast Neoplasms/*radiotherapy/surgery ; Carcinoma, Ductal/*radiotherapy/surgery ; Female ; Humans ; Mastectomy/methods ; *Neoplasm Recurrence, Local/therapy ; Radiotherapy, Adjuvant ; Sentinel Lymph Node Biopsy ; Treatment Failure ; }, abstract = {Women undergoing breast conservation therapy (BCT) for stage 1 breast cancer have adjuvant external beam radiotherapy (EBR). In addition, the use of brachytherapy radiation is being used. We present two local tumor recurrences for review. Our first patient underwent BCT, sentinel lymph node biopsy (SLNBx) and MammoSite brachytherapy for a T1N0M0 infiltrating ductal carcinoma (IDC) of the right breast. Pathology: 0.6 cm poorly differentiated ER, PR, and Her-2/ Neu negative IDC. At 18 months, she had palpable axillary lymph nodes. Fine needle aspiration and ultrasound-guided core biopsy of a nodule showed IDC. She underwent modified radical mastectomy (MRM) and EBR. Our second patient underwent BCT, SLNBx, and MammoSite brachytherapy for a T1N0M0 IDC of the left breast. Pathology: 0.8 cm poorly differentiated, ER+, PR-, and Her-2/Neu negative tumor. At 18 months, a retroareolar mass was detected. Ultrasound guided core needle biopsy showed recurrent IDC. She chose a re-excision and EBR and not MRM. Pathology: 1.3 cm poorly differentiated, ER+, PR-, and Her-2/Neu negative tumor. Our 2 recurrences were >2 cm away from the lumpectomy site and therefor outside the 1 cm treatment plan of the MammoSite catheter. Both recurrences were biologically identical to the initial tumors and are felt to be local failures rather than new primaries.}, } @article {pmid16983530, year = {2006}, author = {Fritzsche, FR and Pahl, S and Petersen, I and Burkhardt, M and Dankof, A and Dietel, M and Kristiansen, G}, title = {Anaplastic large-cell non-Hodgkin's lymphoma of the breast in periprosthetic localisation 32 years after treatment for primary breast cancer--a case report.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {449}, number = {5}, pages = {561-564}, pmid = {16983530}, issn = {0945-6317}, mesh = {Aged ; Breast Implants ; Breast Neoplasms/chemistry/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Ki-1 Antigen/analysis ; Lymphoma, Large B-Cell, Diffuse/chemistry/*pathology/therapy ; }, abstract = {Primary, as well as secondary, lymphomas of the breast are rare diseases and might, in some cases, be misdiagnosed as breast cancer on routine hematoxylin/eosin stainings. We report a case of an anaplastic large cell lymphoma in a 72-year-old woman with a history of breast cancer treated with breast-ablative surgery and a subsequent silicon implant 32 years ago. Clinically, she presented with an ulceration of the skin, which had developed within a few months. On conventional histology, the tumor cells were mimicking poorly differentiated invasive ductal carcinoma with a prominent leukocytic infiltrate. The immunoprofile of the tumor showed negativity for cytokeratins and led to the diagnosis of a CD30-positive anaplastic large cell lymphoma.}, } @article {pmid16980940, year = {2006}, author = {Guo, CC and Epstein, JI}, title = {Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {19}, number = {12}, pages = {1528-1535}, doi = {10.1038/modpathol.3800702}, pmid = {16980940}, issn = {0893-3952}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy, Needle ; Carcinoma, Ductal/chemistry/*pathology/therapy ; Cell Nucleus/pathology ; Combined Modality Therapy ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/pathology ; Prostatic Neoplasms/chemistry/*pathology/therapy ; Treatment Outcome ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) has been described in radical prostatectomies. However, there is limited information as to its histologic features and clinical significance when seen on prostate biopsy. A total of 27 cases of prostate biopsies with only IDC-P (ie no infiltrating cancer anywhere on the biopsy) were studied from the consult files of one of the authors. IDC-P was defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells forming either: (1) solid or dense cribriform patterns or; (2) loose cribriform or micropapillary patterns with either marked nuclear atypia (nuclear size 6 x normal or larger) or comedonecrosis. The numbers of cores involved by IDC-P in the biopsies ranged from 1 to 7, with >1 core involved in 17 cases. The architectural patterns of IDC-P were solid (12), dense cribriform (19), loose cribriform (17), and micropapillary (5). More than one pattern was present in 24 of 27 cases. The cytological features frequently observed in IDC-P were marked pleomorphism (18), non-focal comedonecrosis (22), and mitoses (20). Basal cells were observed on regular hematoxylin and eosin stained slides in 14 cases; in all the cases, basal cells were confirmed by immunohistochemical stains for high molecular weight cytokeratin (n=25) and/or p63 (n = 4). After the diagnosis of IDC-P on prostate biopsies, patients were treated by radical prostatectomy (6), radiation (7), hormone (5), combined radiation and hormone (1), or watchful waiting (2). The follow-up information was not available for six patients. The follow-up times ranged up to 4 years with an average of 2.1 years. In all six radical prostatectomy specimens, high-grade infiltrating carcinoma with Gleason score 8 or 9 was present with five cases also revealing prominent IDC-P. Non-focal extraprostatic extension of carcinoma was observed in five of the six prostatectomy cases with two cases also demonstrating vascular invasion. Three of 16 patients who did not receive radical prostatectomy developed bone metastases. Our study indicates that IDC-P on prostate biopsies is frequently associated with high-grade cancer and poor prognostic parameters at radical prostatectomy as well as potentially advanced disease following other therapies. These findings support prior studies that IDC-P represents an advanced stage of tumor progression with intraductal spread of tumor. Consideration should be given to treat patients with IDC-P on biopsy aggressively even in the absence of documented infiltrating cancer.}, } @article {pmid16978974, year = {2006}, author = {Vo, TN and Meric-Bernstam, F and Yi, M and Buchholz, TA and Ames, FC and Kuerer, HM and Bedrosian, I and Hunt, KK}, title = {Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma.}, journal = {American journal of surgery}, volume = {192}, number = {4}, pages = {552-555}, doi = {10.1016/j.amjsurg.2006.06.020}, pmid = {16978974}, issn = {0002-9610}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/secondary/*therapy ; Carcinoma, Lobular/mortality/secondary/*therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {BACKGROUND: Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC.

METHODS: A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups.

RESULTS: The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group (P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC.

CONCLUSIONS: BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.}, } @article {pmid16978959, year = {2006}, author = {Greene, T and Tartter, PI and Smith, SR and Estabrook, A}, title = {The significance of surgical margins for patients with atypical ductal hyperplasia.}, journal = {American journal of surgery}, volume = {192}, number = {4}, pages = {499-501}, doi = {10.1016/j.amjsurg.2006.06.024}, pmid = {16978959}, issn = {0002-9610}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*etiology ; Carcinoma, Ductal, Breast/*etiology ; Carcinoma, Intraductal, Noninfiltrating/*etiology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/surgery ; Mammary Glands, Human/*pathology/*surgery ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: The significance of surgical margins for patients with atypical ductal hyperplasia is unknown.

PATIENTS AND METHODS: We reviewed our experience with atypical ductal hyperplasia and correlated the margin status of the specimens removed with the risk of recurrence as atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma. Seven hundred forty-seven patients were identified between February 1995 and September 2005 as having biopsy proven atypical ductal hyperplasia (ADH). One hundred fifty-five of these patients were found to have "pure" atypical ductal hyperplasia without associated premalignant or malignant breast disease or a history of ipsilateral disease. Margin status of the initial excisional biopsy was noted and was correlated with the risk of recurrence.

RESULTS: Of the 155 patients whose excisional biopsy specimens were "pure" atypical ductal hyperplasia, 44% (68) had negative margins, 5% (7) had positive margins, and 52% (80) were not reported. No patient underwent re-excision for close or positive margins. Follow-up ranged from 0 to 119 months, with a mean of 26 months. Seven patients (5%) presented with new findings at the site of their initial excisional biopsy, 1 of whom was found to have an invasive ductal carcinoma and 6 of whom had benign findings. Of the 87 patients with margins positive or unknown for ADH at surgical excision, none went on to develop malignancy.

CONCLUSION: Our results suggest that clear surgical margins at surgical excision for atypical ductal hyperplasia did not affect the risk of subsequently developing a malignancy.}, } @article {pmid16978199, year = {2006}, author = {Ciocca, V and Bombonati, A and Gatalica, Z and Di Pasquale, M and Milos, A and Ruiz-Orrico, A and Dreher, D and Folch, N and Monzon, F and Santeusanio, G and Perou, CM and Bernard, PS and Palazzo, JP}, title = {Cytokeratin profiles of male breast cancers.}, journal = {Histopathology}, volume = {49}, number = {4}, pages = {365-370}, doi = {10.1111/j.1365-2559.2006.02519.x}, pmid = {16978199}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms, Male/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Humans ; Immunohistochemistry ; Keratins/*biosynthesis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; }, abstract = {AIMS: The prognostic factors and expression of molecular markers in male breast carcinomas are similar to those in female breast cancers. The identification of distinct cytokeratin (CK) profiles (basal as opposed to luminal cells) helps to identify subsets of tumours with different clinical behaviour. The aim of this study was to investigate CK expression in male breast cancer.

METHODS AND RESULTS: Thirty-two cases of male breast cancer were studied. The panel of CKs studied by immunohistochemistry included: 5/6, 14, 17, 18 and 19. Pathological findings and CK expression were analysed in all cases. Histological patterns included ductal carcinoma in situ, invasive ductal carcinoma and mixed patterns. Four cases were positive for CK5/6 and CK14, identifying a basal-like phenotype. CK17 was negative in all but two cases. All cases expressing either CK5/6 or CK14 were invasive carcinomas of high nuclear and histological grade and were also larger compared with the tumours not expressing CK5/6 and CK14. All tumours except three (also negative for CK5/6) expressed CK18 and CK19. The four basal-like tumours were negative for Her-2 expression.

CONCLUSIONS: Male breast carcinomas have a basal-like phenotype that is similar in frequency to that of female breast carcinomas. The expression of CK5/6 and CK14 identifies a subset of pathologically aggressive male breast cancers.}, } @article {pmid16972643, year = {2006}, author = {Iwasaki, T and Nakagawa, K and Katsura, H and Nakane, S and Kawahara, K and Fukuda, H}, title = {Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron emission scan mimicking lung cancer recurrence.}, journal = {The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi}, volume = {54}, number = {8}, pages = {351-355}, pmid = {16972643}, issn = {1344-4964}, mesh = {Adenocarcinoma/surgery ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/surgery ; Diagnosis, Differential ; False Positive Reactions ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lung Abscess/diagnostic imaging/*etiology/pathology ; Lung Neoplasms/surgery ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*diagnostic imaging ; *Pneumonectomy ; *Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Sutures/*adverse effects ; }, abstract = {We present the case of a 57-year-old woman with pulmonary suture abscess. She had undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and right breast-conserving surgery for invasive ductal carcinoma 5 months previously, followed by irradiation plus endocrine therapy. Chest radiography and computed tomography revealed an irregular mass (3.5 cm in diameter) between the residual S1 segment and the middle lobe, neighboring the staple line of the segmentectomy. 18F-fluorodeoxyglucose uptake into the mass increased, seen by positron emission scans. Therefore, we could not rule out the possibility of local recurrence of lung cancer and resected it. Pathologically and microbiologically, the mass was a suture abscess arising around the nylon suture of the previous segmentectomy. This lesion was the result of a foreign-body reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the segmentectomy and breast-conserving surgery may also have contributed to this condition.}, } @article {pmid16969029, year = {2006}, author = {Ohsako, T and Inoue, K and Nagamoto, N and Yoshida, Y and Nakahara, O}, title = {[Two cases of recurrent breast cancer with regional lymph node metastases showing a complete response to trastuzumab and paclitaxel treatment].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {33}, number = {9}, pages = {1301-1303}, pmid = {16969029}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {We report two cases of recurrent breast cancer with regional lymph node metastases that responded completely to treatment with trastuzumab and paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer, underwent mastectomy and axillary lymph node dissection in July 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic and blood vessels, negative nodal status (0/11), negative ER/PgR status, and overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin and cyclophosphamide were administered from January 2003; however, they were not effective. The patient showed a complete response after three months of chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in September 2003. She has maintained a complete response for two and a half years and was not administered any further treatment as of February 2006. Case 2: A 59-year-old woman, who presented with right breast cancer, underwent mastectomy and axillary lymph node dissection in May 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological grade 2, positive invasion to the lymphatic and blood vessels, negative nodal status (0/5), positive ER and uncertain PgR status, and overexpression of HER 2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a right supraclavicular lymph node metastasis was noted in October 2004. Treatment with exemestane was not effective. However, a complete response was observed with trastuzumab and paclitaxel for four months. She has maintained a complete response for six months and was not administered any further treatment as of February 2006.}, } @article {pmid16969028, year = {2006}, author = {Rai, Y and Takahama, T and Sagara, Y and Sagara, Y and Matsuyama, Y and Ando, M and Sagara, Y and Ooi, Y}, title = {[Markedly effective regimen using bi-weekly trastuzumab and paclitaxel in an advanced breast cancer with multiple liver metastases].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {33}, number = {9}, pages = {1297-1300}, pmid = {16969028}, issn = {0385-0684}, mesh = {Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary ; Drug Administration Schedule ; Female ; Humans ; Liver Neoplasms/*secondary ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {A 69-year-old woman had a 7 x 6 cm tumor on her left breast with ipsilateral axillary lymph node swelling and multiple liver metastases as detected on CT scan (T 3 N 2 M 1 b, Stage IV). Core needle biopsy and immunohistochemistry of breast tumor showed invasive ductal carcinoma with negative hormone receptor and overexpression of HER 2. After a treatment failure of 3 months weekly trastuzumab monotherapy, a combination of bi-weekly trastuzumab and paclitaxel (weekly 6, bi-weekly 9 courses), was given. Tumor markers became negative 4 months later, and multiple liver nodules, breast tumor and axillary nodes completely disappeared 9 months later. Breast surgery was avoided, and CR was maintained more than 8 months only with bi-weekly trastuzumab. From the standpoint of the patient's convenience,a bi-weekly schedule of trastuzumab and paclitaxel could be a promising treatment choice for metastatic breast cancer.}, } @article {pmid16966164, year = {2006}, author = {Campos, LM and Cavalcanti, CL and Lima-Filho, JL and Carvalho, LB and Beltrão, EI}, title = {Acridinium ester conjugated to lectin as chemiluminescent histochemistry marker.}, journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals}, volume = {11}, number = {5}, pages = {480-484}, doi = {10.1080/13547500600742169}, pmid = {16966164}, issn = {1354-750X}, mesh = {Acridines/*chemistry ; Biomarkers, Tumor/*analysis ; Breast/*chemistry ; Breast Neoplasms/*chemistry ; Humans ; Lectins/*chemistry ; Luminescence ; }, abstract = {Cell differentiation/dedifferentiation includes changes in oligosaccharide composition and distribution in the cell surface glycoconjugates. Lectins have been used as auxiliary tools in histopathological diagnosis of mammary, uterus and brain pathologies. Acridinium ester (AE) conjugated to biomolecules has been employed in chemiluminescent analytical applications. This work aimed to use a lectin, concanavalin A (Con A), conjugated to AE as a chemiluminescent histochemistry tool. Biopsies of normal and infiltrating duct carcinoma (IDC) of mammary tissues were treated by a Con A-AE derivative. Photon emission, observed during the breakage of the chemical bound between Con A and AE, was quantified, expressed in relative light units (RLU) and correlated to the labelling of the normal and transformed tissues. The results demonstrated that RLU presented a linear relationship with the labelled tissue area in the range 0.125-1.0 cm2 (r=0.98). Furthermore, RLU was much higher for the IDC (1283.920x103+/-220.621x103) than the normal tissue (2.565x103+/-0.247x103), namely, about 500 times higher. The Con A-AE conjugation efficiency, differential staining of normal and IDC tissues, and quantification of results contribute to a decrease in the subjectivity in routine histopathological diagnoses and indicate that acrydinum ester can join other lectin marker to be used in histochemistry.}, } @article {pmid16959899, year = {2006}, author = {Santegoets, SJ and Masterson, AJ and van der Sluis, PC and Lougheed, SM and Fluitsma, DM and van den Eertwegh, AJ and Pinedo, HM and Scheper, RJ and de Gruijl, TD}, title = {A CD34(+) human cell line model of myeloid dendritic cell differentiation: evidence for a CD14(+)CD11b(+) Langerhans cell precursor.}, journal = {Journal of leukocyte biology}, volume = {80}, number = {6}, pages = {1337-1344}, doi = {10.1189/jlb.0206111}, pmid = {16959899}, issn = {0741-5400}, mesh = {Antigens, CD/biosynthesis/immunology ; Antigens, CD34/*immunology/metabolism ; CD11b Antigen/*immunology/metabolism ; Cell Differentiation/*immunology ; Cell Line, Tumor ; Cell Proliferation ; Cytoplasmic Granules/immunology/metabolism ; Gene Expression Regulation/immunology ; Humans ; Langerhans Cells/*immunology/metabolism ; Lectins, C-Type/biosynthesis/immunology ; Lipopolysaccharide Receptors/*immunology/metabolism ; Mannose-Binding Lectins/biosynthesis/immunology ; *Models, Immunological ; Myeloid Progenitor Cells/immunology/metabolism ; }, abstract = {The study of early events in dendritic cell (DC) differentiation is hampered by the lack of homogeneous primary cell systems that allow the study of cytokine-driven, transitional DC differentiation steps. The CD34(+) acute myeloid leukemia cell line MUTZ-3 displays a unique ability to differentiate into interstitial DC (IDC) and Langerhans cells (LC) in a cytokine-dependent manner. Phenotypic characterization revealed MUTZ-3 to consist of three distinct subpopulations. Small CD34(+)CD14(-)CD11b(-) progenitors constitute the proliferative compartment of the cell line with the ability to differentiate through a CD34(-)CD14(-)CD11b(+) stage to ultimately give rise to a morphologically large, nonproliferating CD14(+)CD11b(hi) progeny. These CD14(+)CD11b(hi) cells were identified as common, immediate myeloid DC precursors with the ability to differentiate into LC and IDC, exhibiting characteristic and mutually exclusive expression of Langerin and DC-specific ICAM-grabbing nonintegrin, respectively. The identity of the MUTZ-3-derived LC subset was confirmed further by the presence of Birbeck granules. We conclude that the MUTZ-3 cell line provides a ready and continuous supply of common myeloid precursors, which should facilitate further study of the ontogeny of myeloid DC lineages.}, } @article {pmid16958958, year = {2006}, author = {Patterson, SK and Helvie, MA and Aziz, K and Nees, AV}, title = {Outcome of men presenting with clinical breast problems: the role of mammography and ultrasound.}, journal = {The breast journal}, volume = {12}, number = {5}, pages = {418-423}, doi = {10.1111/j.1075-122X.2006.00298.x}, pmid = {16958958}, issn = {1075-122X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; Breast/*pathology ; Breast Diseases/*diagnosis/diagnostic imaging/pathology ; Breast Neoplasms, Male/diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; Humans ; Male ; *Mammography ; Middle Aged ; Prevalence ; Retrospective Studies ; *Ultrasonography, Mammary ; }, abstract = {The purpose of this study was to determine the outcome of men presenting with clinical breast problems for breast imaging and to evaluate the role of mammography and ultrasound in the diagnosis of benign and malignant breast problems. We retrospectively reviewed clinical, radiographic, and pathologic records of 165 consecutive symptomatic men presenting to Breast Imaging over a 4 year period. We assessed the clinical indication for referral, mammographic findings, sonographic findings, histologic results, and clinical outcomes. Patients ranged in age from 22 to 96 years. Breast Imaging Reporting and Data System (BI-RADS) category 4 and 5 mammograms and solid sonographic masses were considered suspicious for malignancy. Six of 165 men (4%) had primary breast carcinoma, which were mammographically suspicious in all 6 (100%). Five were invasive ductal carcinoma and one was ductal carcinoma in situ (DCIS). Of 164 mammograms, 20 (12%) were suspicious. Six were cancer and 14 were benign. Clinical follow-up for 2 years or biopsy results were available for 138 of the 165 men (84%). Twelve with benign mammographic findings had benign biopsies. All men with benign mammography not undergoing biopsy were cancer free. Sensitivity for cancer detection (mammography) was 100% and specificity was 90%. Positive predictive value (mammography) was 32% (6 of 19) and the negative predictive value was 100%. Sonography was performed in 68 of the 165 men (41%). Three of three cancers (100%) were solid sonographic masses. There were 9 of 68 false-positive examinations (13%). Sensitivity and negative predictive value for cancer detection (ultrasound) was 100% and specificity was 74%. The most common clinical indication for referral was mass/thickening (56%). Mammography had excellent sensitivity and specificity for breast cancer detection and should be included as the initial imaging examination of men with clinical breast problems. The negative predictive value of 100% for mammography suggests that mammograms read as normal or negative need no further examination if the clinical findings are not suspicious. A normal ultrasound in these men confirms the negative predictive value of a normal mammogram.}, } @article {pmid16951894, year = {2006}, author = {de Moraes, AB and Zanini, RR and Turchiello, MS and Riboldi, J and de Medeiros, LR}, title = {[Survival study of breast cancer patients treated at the hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil].}, journal = {Cadernos de saude publica}, volume = {22}, number = {10}, pages = {2219-2228}, doi = {10.1590/s0102-311x2006001000028}, pmid = {16951894}, issn = {0102-311X}, mesh = {Adult ; Biomarkers, Tumor/blood ; Brazil/epidemiology ; Breast Neoplasms/*mortality/pathology/therapy ; Cohort Studies ; Female ; Humans ; Lymph Nodes/*pathology/surgery ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; }, abstract = {This retrospective hospital-based study aimed to describe health conditions and to estimate the survival of 252 patients diagnosed with breast cancer and treated at the Mastology Outpatient Clinic at the University Hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil, from 1980 to 2000. Analysis followed the Kaplan-Meier and Cox model. Mean age was 54, and 73.4% of the patients had a histological diagnosis of invasive ductal carcinoma, 63.9% showed no lymph node involvement, and 57.6% were clinical stage II. At the end of the study, 64.7% were alive and free of breast cancer and 5.1% had died of other causes. Five-year survival was 87.7% for all women, and prognostic factors associated with survival were tumor size (HR = 12.03; > 5cm), lymph node involvement (HR = 3.08; N1) and number (HR = 4.66; None), and estrogen (HR = 0.34) and c-erbB-2 (HR = 2.51) receptors. Based on the results, intensive awareness-raising campaigns are vitally important for implementing breast cancer screening to achieve early diagnosis.}, } @article {pmid16951768, year = {2006}, author = {Erkus, M and Meteoglu, I and Culhaci, N and Meydan, N and Erdogdu, I}, title = {Does thymidine phosphorylase correlate with angiogenesis in intraductal carcinoma of the breast?.}, journal = {Saudi medical journal}, volume = {27}, number = {9}, pages = {1329-1333}, pmid = {16951768}, issn = {0379-5284}, mesh = {Adult ; Aged ; Antigens, CD34/analysis/metabolism ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/blood supply/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neovascularization, Pathologic/*metabolism ; Observer Variation ; Prognosis ; Thymidine Phosphorylase/analysis/*metabolism ; Turkey ; }, abstract = {OBJECTIVE: To determine the association between thymidine phosphorylase (TP) and angiogenesis, and other conventional prognostic markers. We also evaluated interobserver and intraobserver reliability for TP expression in ductal carcinoma, to achieve a more consistent results.

METHODS: Our study included all cases diagnosed in Adnan Menderes University Medical Faculty Hospital, Aydin, Turkey as invasive ductal carcinoma or ductal carcinoma in situ (DCIS) with proven component of (>30%), between January 2003 and February 2005. The total number of the cases was 27 and their median age was 50 years. All sections were stained using monoclonal antibody-TP and examined at x40 magnification. Either nuclear or cytoplasmic staining was accepted as positive. The histoscore (H-score) was calculated for each specimen. The tumor stromal vascularity was assessed by monoclonal anti-CD34; and areas of intense vascularization were determined. Conventional immunohistochemical markers such as c-erb B2, Ki-67, estrogen and progesterone receptors and p53 were also applied to all slides. Three pathologists blindly examined each slide under 10 high-power fields (10 HPF) for 2 times in a 2 months period.

RESULTS: There was no significant association between stromal vascularity and TP staining of cancer cells (p=0.1) and no correlation was determined between H-scores for TP staining in ductal carcinoma and DCIS components (p=0.5).

CONCLUSION: There was no significant correlation noted between stromal and periductal vascularity with the anti-CD34 antibody was used. No significant correlation was identified between the TP H-score and stromal or periductal vascularity.}, } @article {pmid16951342, year = {2006}, author = {Charbonnier, LM and van Duivenvoorde, LM and Apparailly, F and Cantos, C and Han, WG and Noël, D and Duperray, C and Huizinga, TW and Toes, RE and Jorgensen, C and Louis-Plence, P}, title = {Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {177}, number = {6}, pages = {3806-3813}, doi = {10.4049/jimmunol.177.6.3806}, pmid = {16951342}, issn = {0022-1767}, mesh = {Adoptive Transfer ; Animals ; Arthritis, Experimental/*immunology/pathology/*prevention & control ; B-Lymphocyte Subsets/immunology/metabolism ; Cell Differentiation/immunology ; *Cell Proliferation ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology/transplantation ; Injections, Intraperitoneal ; Integrin alpha2/*biosynthesis ; Interleukin-10/biosynthesis/metabolism ; Lymph Nodes/cytology/immunology/metabolism ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory/*immunology/metabolism/*pathology ; }, abstract = {Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ alpha-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of < 10(5) TCRbeta+ CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.}, } @article {pmid16949910, year = {2006}, author = {Shen, D and Nooraie, F and Elshimali, Y and Lonsberry, V and He, J and Bose, S and Chia, D and Seligson, D and Chang, HR and Goodglick, L}, title = {Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis.}, journal = {Human pathology}, volume = {37}, number = {12}, pages = {1583-1591}, doi = {10.1016/j.humpath.2006.06.001}, pmid = {16949910}, issn = {0046-8177}, support = {CA-86366/CA/NCI NIH HHS/United States ; }, mesh = {Annexin A1/*biosynthesis ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Disease Progression ; Humans ; Hyperplasia/metabolism ; Immunohistochemistry ; Lymphatic Metastasis/pathology ; *Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and a known mediator of glucocorticoid-regulated inflammatory responses. Using a combined multiple high-throughput approach, we recently identified a reduced expression of ANXA1 in human breast cancer. The finding was confirmed at the gene level by quantitative reverse transcription-polymerase chain reaction and at the protein level by immunohistochemical staining of normal, benign, and malignant breast tissues. In this study, we constructed and used a high-density human breast cancer tissue microarray to characterize the expressional pattern of ANXA1 according to histopathologies. The tissue microarray contains 1,158 informative breast tissue cores of different histologies including normal tissues, hyperplasia, in situ and invasive tumors, and lymph node metastases. Our results showed that there was a significant decrease in glandular expression of ANXA1 in ductal carcinoma in situ and invasive ductal carcinoma compared with either normal breast tissue or hyperplasia (P < .0001). Moreover, in benign breast tissue, myoepithelial cells showed strong expression of ANXA1. There was a decrease of ANXA1 expression in myoepithelial cells in ductal carcinoma in situ lesions compared with the same cell population in either normal or hyperplastic lesions. These results suggest that suppressed ANXA1 expression in breast tissue is correlated with breast cancer development and progression.}, } @article {pmid16942646, year = {2006}, author = {Lopes, G and DeCesare, T and Ghurani, G and Vincek, V and Jorda, M and Glück, S and Silva, O}, title = {Primary ectopic breast cancer presenting as a vulvar mass.}, journal = {Clinical breast cancer}, volume = {7}, number = {3}, pages = {278-279}, doi = {10.3816/CBC.2006.n.041}, pmid = {16942646}, issn = {1526-8209}, mesh = {Adenocarcinoma/*diagnosis/secondary/therapy ; Adult ; *Breast ; Breast Neoplasms/*diagnosis/pathology/therapy ; Choristoma/*diagnosis/pathology/therapy ; Diagnosis, Differential ; Female ; Humans ; Neoplasms, Hormone-Dependent/*diagnosis/pathology/therapy ; Vulvar Neoplasms/*diagnosis/secondary/therapy ; }, abstract = {Ectopic breast tissue is found along the primitive embryonic milk lines, which extend from the axilla to the groin. Rarely, its occurrence has been described in the vulva. We report a patient who developed primary adenocarcinoma of ectopic breast tissue in such a location and present a review of the pertinent medical literature. The predominant pathology is that of invasive ductal carcinoma; however, other tumor types have also been reported in accessory breast tissue. Its treatment usually entails surgical resection with lymph node dissection. Adjuvant therapy should be guided by the same principles as in orthotopic breast carcinoma.}, } @article {pmid16941124, year = {2007}, author = {Igyártó, BZ and Magyar, A and Oláh, I}, title = {Origin of follicular dendritic cell in the chicken spleen.}, journal = {Cell and tissue research}, volume = {327}, number = {1}, pages = {83-92}, doi = {10.1007/s00441-006-0250-0}, pmid = {16941124}, issn = {0302-766X}, mesh = {Animals ; B-Lymphocytes/cytology/immunology ; Cell Differentiation ; Cell Movement ; Chickens/*physiology ; Dendritic Cells, Follicular/*cytology/enzymology/immunology ; Fluorescent Antibody Technique, Indirect ; Immunoenzyme Techniques ; Spleen/*cytology ; T-Lymphocytes/cytology/immunology ; beta-Galactosidase/immunology/metabolism ; }, abstract = {The ellipsoid-associated cell (EAC) is a blood-borne phagocytic cell, residing in the antigen trapping zone of the chicken spleen. Binding and endocytosis of betaGalactosidase (betaGal) are independent from the Fc and complement receptors, because sulfated polysaccharides, in a concentration manner, inhibit the bacterial antigen uptake. The betaGal-positive cells migrate to the periarterial lymphatic sheath (PALS), the preexisting germinal centers (GC), and form clusters with B- and T-cells. betaGal, E5G12 double positive cells on the surface of the ellipsoid and in the PALS, GC and clusters prove that the EACs carry the enzyme. The EAC and the follicular dendritic cell (FDC) express, 68.2 and E5G12 and, 74.3 and E5G12, antigens, respectively. During migration the cessation of 68.2 and expression of 74.3 indicate the differentiation of EAC to FDC. By day 14 the clusters had disappeared, and in several GC the presence of double positive cells (74.3 and betaGal; E5G12 and betaGal) showed that the clusters had developed to GC. The presence of betaGal(+) cells in the PALS, where interdigitating dendritic cells (IDC) cooperate with the T-cells, suggests that in the spleen alternate routes exist for the EAC differentiation to FDC: EAC to FDC: betaGal-loaded cells in the preexisting GC; and EAC through IDC to FDC: betaGal(+) EAC in the PALS and clusters. The EAC-FDC axis works exclusively inside the spleen; therefore; this system may be operated in pneumococcus infection.}, } @article {pmid16941011, year = {2006}, author = {Dabbs, DJ and Chivukula, M and Carter, G and Bhargava, R}, title = {Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {19}, number = {11}, pages = {1506-1511}, doi = {10.1038/modpathol.3800678}, pmid = {16941011}, issn = {0893-3952}, mesh = {Actins/analysis ; Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/pathology ; DNA-Binding Proteins/analysis ; ErbB Receptors/analysis ; Female ; Humans ; *Immunohistochemistry ; Keratin-14/analysis ; Keratin-17/analysis ; Keratin-5/analysis ; Keratin-6/analysis ; Necrosis ; Neoplasm Invasiveness ; Phenotype ; Proto-Oncogene Proteins c-kit/analysis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Trans-Activators/analysis ; Transcription Factors ; Tumor Suppressor Proteins/analysis ; Vimentin/analysis ; }, abstract = {The basal phenotype of breast carcinoma was demonstrated from a study of gene expression profiles, which demonstrated five carcinoma phenotypes with differing immunohistologic profiles and outcomes. The basal phenotype, so-named because of an immunohistologic profile that is similar to myoepithelial cells of the breast, has poor outcomes. While the invasive basal phenotype has been described, there is a paucity of literature regarding the existence or recognition of a precursor lesion. We searched our CoPath database for breast carcinomas in the age group of 37 years or less, and this yielded 98 cases from the years 2001 to April 2006. Pathology reports were screened for those cases that were negative for estrogen and progesterone receptors and HER-2/neu (triple negative). A total of 16 cases (16/98, 16%) fulfilled these criteria. Histology was reviewed and immunostains were performed for Cytokeratins 14, 17, and 5/6, vimentin, EGFR, c-kit, smooth muscle actin and p63. All 16 cases had a high-grade invasive ductal carcinoma, Nottingham score 9/9, with geographic necrosis, good circumscription and lymphoid infiltrates. Of the 16 cases, 13 exhibited at least one area of ductal carcinoma in situ (DCIS). The DCIS types were solid, flat or micropapillary, high nuclear grade, with comedonecrosis and invariably associated with intense lymphoid inflammatory cell infiltration. Of 16 invasive cases, 14 (88%) were positive for CK14, CK17, CK5/6 and EGFR; 94% were vimentin positive, while half or less of cases were positive for smooth muscle actin, c-kit or p63. All of the DCIS components demonstrated the same immunohistologic profile as the invasive component. A DCIS component of solid, flat or micropapillary type exists in the basal phenotype of breast carcinoma, and it demonstrates the same immunophenotype as the invasive carcinoma, typically positive for CK5/6, CK14, CK17, vimentin and EGFR, but negative for ER/PR and HER-2/neu.}, } @article {pmid16938528, year = {2006}, author = {Kim, MJ and Ro, JY and Ahn, SH and Kim, HH and Kim, SB and Gong, G}, title = {Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes.}, journal = {Human pathology}, volume = {37}, number = {9}, pages = {1217-1226}, doi = {10.1016/j.humpath.2006.04.015}, pmid = {16938528}, issn = {0046-8177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/mortality/*pathology ; Breast Neoplasms, Male/metabolism/mortality/*pathology ; ErbB Receptors/biosynthesis ; Female ; Humans ; Immunohistochemistry ; Infant, Newborn ; Keratins/biosynthesis ; Male ; Middle Aged ; Phenotype ; Prognosis ; Proto-Oncogene Proteins c-kit/biosynthesis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*biosynthesis ; Receptors, Progesterone/*biosynthesis ; Survival Analysis ; Tumor Suppressor Protein p53/biosynthesis ; }, abstract = {DNA microarray profiling studies have led to the classification of invasive breast carcinoma into luminal/estrogen receptor-positive, normal breast-like, Her2/neu-overexpressing, and basal-like types. Among these groups, the basal-like subtype is associated with the poorest clinical outcome in Western countries. To date, the clinicopathologic characteristics of the basal-like carcinomas, compared with other subtypes, have not been described in the Korean population. In this study, we used tissue microarray to examine the expression of basal cytokeratins (CK) (CK5 and CK14) and luminal CK (CK8/18), epidermal growth factor receptor, c-kit, hormone receptors (HRs), p53, and Her2/neu in 776 consecutive patients diagnosed with invasive breast carcinoma from January 1993 to December 1998 and categorized these cases into 5 subgroups (basal-like, HR-expressing, Her2/neu-overexpressing, HR and Her2/neu-expressing, and null subtypes negative for all markers), based on the immunohistochemical data. We identified cases of 114 (14.7%) basal-like, 345 (44.5%) HR-expressing, 133 (17.1%) Her2/neu-overexpressing, 61 (7.8%) HR and Her2/neu-expressing, and 123 (15.9%) null subtypes. Histologically, most basal-like breast cancers were invasive ductal carcinoma, not otherwise specified (98 cases, 86.0%), with high nuclear and/or histologic grades, and most metaplastic carcinomas (6 [75.0%] of 8 cases) were the basal-like subtype. Both basal-like and Her2/neu-overexpressing subtypes were associated with larger tumor sizes (mean, 3.6 and 3.3 cm, respectively) than the HR-expressing group (mean, 2.8 cm) (P = .001 and P = .036, respectively). Nodal stage of Her2/neu-overexpressing subtype was higher than that of basal-like subtype; however, overall stage was not different between the 2 groups (P = .010 and .123, respectively). Distant metastasis was most frequently observed in the Her2/neu-overexpressing subtype (33.8%), which was prognostically the worst subgroup of breast cancers. In contrast to previous findings from Western countries, our analyses reveal that the Her2/neu status is the most important prognostic factor of breast cancers.}, } @article {pmid16937310, year = {2006}, author = {Hikino, H and Kawashima, M and Yamada, T and Ozaki, N}, title = {Motor dominant neuropathy induced by adjuvant therapy with adriamycin and cyclophosphamide followed by dose-dense paclitaxel in a breast cancer patient.}, journal = {International journal of clinical oncology}, volume = {11}, number = {4}, pages = {332-335}, pmid = {16937310}, issn = {1341-9625}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Chemotherapy, Adjuvant/adverse effects ; Cyclophosphamide/*administration & dosage ; Dose-Response Relationship, Drug ; Doxorubicin/*administration & dosage ; Female ; Humans ; Motor Neuron Disease/chemically induced ; Paclitaxel/*administration & dosage ; Peripheral Nervous System Diseases/*chemically induced ; }, abstract = {A 38-year-old woman underwent mastectomy and axillary lymph node dissection for invasive ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) followed by weekly paclitaxel 80 mg/m(2) (without interruption) as adjuvant treatment. After receiving ten courses of paclitaxel, the patient developed motor neuropathy, with difficulty in ascending stairs and rising from a chair. A nerve conduction study demonstrated impairment of bilateral peroneal nerve function, although the sural sensory nerves were intact. After 2 weeks of withholding paclitaxel treatment, the motor neuropathy was alleviated and the scheduled doses were completed. A pharmacokinetic study of paclitaxel showed the possibility of elimination delay at the last infusion. We suggest that a dose-dense schedule of paclitaxel may be a significant risk factor for this kind of motor neuropathy.}, } @article {pmid16933716, year = {2006}, author = {Ohri, A and Jetly, D and Shukla, K and Bansal, R}, title = {Cytological grading of breast neoplasia and its correlation with histological grading.}, journal = {Indian journal of pathology & microbiology}, volume = {49}, number = {2}, pages = {208-213}, pmid = {16933716}, issn = {0377-4929}, mesh = {Adult ; Breast Neoplasms/*pathology ; Cytodiagnosis ; Female ; Histological Techniques ; Humans ; Middle Aged ; Retrospective Studies ; }, abstract = {Cytological grading of breast cancer is not well established despite histological grading having gained a strong foothold. In our study we have analyzed 50 cases of breast carcinoma which included invasive ductal carcinoma, invasive lobular carcinoma, mucinous carcinoma, stromal sarcoma, apocrine carcinoma, papillary carcinoma. Papanicolaou smears were graded according to established Hunt's, Simplified Black and Modified Black grading systems. They were then compared with the Scarff Bloom Richardson grading system. Simplified Black grading system has been recommended for cytological grading of breast neoplasia because of its lucidity and its reproducibility. Cytological grading of breast neoplasia is important for neo adjuvant chemotherapy and also for predicting the prognosis of the patient on FNAC alone. Incorporation of other parameters like apoptosis and bcl-2 is also recommended.}, } @article {pmid16932086, year = {2006}, author = {La Vecchia, L and Varotto, L and Zanolla, L and Spadaro, GL and Fontanelli, A}, title = {Right ventricular function predicts transplant-free survival in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {7}, number = {9}, pages = {706-710}, doi = {10.2459/01.JCM.0000243006.90170.ce}, pmid = {16932086}, issn = {1558-2027}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/mortality/*physiopathology ; Coronary Angiography ; Female ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Stroke Volume ; Ventricular Dysfunction, Left/etiology ; Ventricular Dysfunction, Right/*etiology ; }, abstract = {BACKGROUND: Right ventricular function may be reduced in patients with idiopathic dilated cardiomyopathy (IDC). The prognostic implications of right ventricular dysfunction have not been investigated in this group of patients.

METHODS: In a series of 120 consecutive patients with IDC [defined as a left ventricular ejection fraction (LVEF) < 55%, normal coronary arteries and no other causes for left ventricular dysfunction], right ventricular function was prospectively evaluated by means of angiocardiography at the time of catheterization. A head-to-head comparison of ventricular volumes, ejection fraction, end-diastolic pressure, stroke work index and end-systolic pressure/volume ratio of the left and right ventricle was performed according to the Cox's proportional hazard method for the pre-defined end-point of transplant-free survival.

RESULTS: In the study population, LVEF was 31 +/- 11% and right ventricular ejection fraction (RVEF) was 34 +/- 10%. After a mean follow-up of 30 months (range 12-120 months), 26 patients died (22%) and 14 (12%) underwent heart transplantation. At univariate analysis, all the above mentioned parameters were significantly (P < 0.0001) associated with outcome except left and right ventricular end-systolic pressure/volume ratio. At multivariate analysis, independent predictors of transplant-free survival were RVEF (P = 0.001), right ventricular stroke work index (P = 0.015), right ventricular end-diastolic volume (P = 0.034) and left ventricular end-diastolic volume (P = 0.048), but not LVEF. The same relation holds true considering the end point of total mortality.

CONCLUSIONS: Parameters of right ventricular function are strong predictors of survival in IDC, even in patients enrolled over a wide range of LVEFs. The present study suggests that right ventricular function should be evaluated in patients with IDC. A large non-invasive based study on right ventricular function in IDC appears to be warranted.}, } @article {pmid16932083, year = {2006}, author = {Barbieri, A and Grigioni, F and Bursi, F and Reggianini, L and Bonatti, S and Ricci, C and Boriani, G and Russo, A and Magelli, C and Branzi, A and Modena, MG}, title = {Role of severe functional mitral regurgitation in predicting electrical remodeling in idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {7}, number = {9}, pages = {691-695}, doi = {10.2459/01.JCM.0000243003.05418.d4}, pmid = {16932083}, issn = {1558-2027}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*physiopathology ; Electrocardiography ; Female ; Heart Conduction System/*physiopathology ; Heart Ventricles/physiopathology ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency/complications/*physiopathology ; Multivariate Analysis ; Myocardial Contraction/physiology ; Prognosis ; Risk Assessment ; }, abstract = {OBJECTIVE: To investigate incidence and predictors of clinically relevant QRS widening (predefined as > or = 10% with respect to baseline) in idiopathic dilated cardiomyopathy (IDC) and particularly the prognostic role of functional mitral regurgitation (MR). Although QRS widening in left ventricular systolic dysfunction carries relevant prognostic and therapeutic implications, its incidence and predictors in patients with IDC remain unknown.

METHODS: We analyzed 114 patients with IDC receiving optimized medical treatment (age 52 +/- 10 years; 44% males; 36% New York Heart Association class III-IV) who underwent clinical, echocardiographic, hemodynamic, and laboratory evaluations and at least two electrocardiograms > or = 6 months after the index evaluation.

RESULTS: During follow-up (median 20 months), 19 (17%) patients developed clinically relevant QRS widening, corresponding to an incidence of 8% per year. At multivariable analysis, the presence of echocardiographically detected severe MR (P = 0.029) and mean right atrial pressure (RAP) by right heart catheterization (P = 0.021) independently predicted clinically relevant QRS widening.

CONCLUSIONS: Clinically relevant QRS widening is relatively frequent in IDC despite optimized medical treatment, and is independently predicted by MR severity and high RAP. IDC patients presenting either of these risk-factors might benefit from strict follow-up, which could also allow timely detection of the onset of indications for cardiac resynchronization therapy.}, } @article {pmid16930336, year = {2006}, author = {Horii, R and Akiyama, F and Ikenaga, M and Iwase, T and Sakamoto, G}, title = {Muco-epidermoid carcinoma of the breast.}, journal = {Pathology international}, volume = {56}, number = {9}, pages = {549-553}, doi = {10.1111/j.1440-1827.2006.02004.x}, pmid = {16930336}, issn = {1320-5463}, mesh = {Aromatase Inhibitors/therapeutic use ; Breast Neoplasms/drug therapy/*pathology/surgery ; Carcinoma, Mucoepidermoid/drug therapy/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Japan ; Lymphatic Metastasis/pathology ; Mammography ; Middle Aged ; Postmenopause ; Ultrasonography, Mammary ; }, abstract = {A very rare case of muco-epidermoid carcinoma of the breast is reported. A 54-year-old woman noticed a breast lump and consulted the Cancer Institute Hospital, Tokyo. Physical examination revealed a mass with an unclear margin in the upper outer area of the left breast. Both mammography and ultrasonography showed an irregularly shaped mass, suggesting invasive carcinoma. Aspiration cytology revealed solid clusters of two types of cancer cells: ones with mucus in the cytoplasm, and others without mucus. Cytological features resembled muco-epidermoid carcinoma of the salivary gland but it was not possible to establish a diagnosis of the histological type because muco-epidermoid carcinoma of the breast had not previously been encountered by the authors. After incisional biopsy, left mastectomy with axillary lymph node dissection was performed. Histologically the tumor was surrounded by a fibrous pseudocapsule and was composed of intraductal carcinoma foci and invasive cancer nests. Intraductal carcinoma foci were the low papillary type. Stromal invasion showed many solid nests composed of mucus-containing and squamoid cancer cells. There was no common invasive ductal carcinoma component in this tumor. These histological features confirmed the diagnosis as muco-epidermoid carcinoma of the breast. This is the first report of muco-epidermoid carcinoma of the breast in Japan.}, } @article {pmid16929128, year = {2006}, author = {Kijima, Y and Umekita, Y and Ehi, K and Yoshinaka, H and Funasako, Y and Owaki, T and Yoshida, H and Aikou, T}, title = {Sudden hemorrhage without skin invasion in a patient with breast cancer: a case report and literature review.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {3}, pages = {317-321}, doi = {10.2325/jbcs.13.317}, pmid = {16929128}, issn = {1340-6868}, mesh = {Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*complications/diagnostic imaging ; Carcinoma, Ductal, Breast/complications/diagnostic imaging ; Female ; Hemorrhage/*etiology ; Humans ; Mammography ; Mastectomy ; Neoplasm Invasiveness/*pathology ; Skin/*pathology ; Tomography, X-Ray Computed ; }, abstract = {We report a rare case of sudden hemorrhage caused by breast cancer. A 70-year-old Japanese woman noted fresh bleeding from her left breast. On physical examination, continuous hemorrhage accompanied by an open cavity was observed in the left breast. Mammography and ultrasonography revealed a well-circumscribed mass, with solid and cystic components, that was highly suggestive of intracystic breast carcinoma with direct skin invasion. Computed tomography and bone scintigraphy showed no distant metastasis. Aspiration biopsy of the lesion showed several clusters of adenocarcinoma cells. Modified radical mastectomy was performed with a presumptive diagnosis of stage III B left breast cancer. Invasive ductal carcinoma without skin invasion was diagnosed histologically. To the best of our knowledge, only 6 other cases of sudden hemorrhage caused by breast cancer without skin invasion have been reported in Japan. We review the literature and discuss the clinical characteristics of this unusual phenomenon.}, } @article {pmid16917774, year = {2006}, author = {Buchanan, JJ and Park, JH and Shea, CH}, title = {Target width scaling in a repetitive aiming task: switching between cyclical and discrete units of action.}, journal = {Experimental brain research}, volume = {175}, number = {4}, pages = {710-725}, pmid = {16917774}, issn = {0014-4819}, mesh = {Adaptation, Physiological/*physiology ; Adult ; Arm/innervation/physiology ; Biological Clocks/physiology ; Biomechanical Phenomena ; Brain/physiology ; Humans ; Joints/physiology ; Learning/*physiology ; Movement/*physiology ; Muscle, Skeletal/innervation/physiology ; Nerve Net/physiology ; Orientation/*physiology ; Periodicity ; Psychomotor Performance/*physiology ; Range of Motion, Articular/physiology ; Space Perception/*physiology ; Time Factors ; }, abstract = {An aiming task was used to identify the processes whereby the motor system adapted a repetitive aiming action to systematic changes in ID (ID = log(2)(2A/W), Fitts in J Exp Psychol 47:381-391, 1954) within a single trial. Task ID was scaled in a trial by moving the outside edge of two stationary targets to produce nine different target IDs in a trail. The ID within a trial was scaled in one of two directions: (1) an increasing ID condition, starting with an ID = 3.07 and ending with an ID = 5.91; and (2) a decreasing ID condition, starting with an ID = 5.91 and ending with an ID = 3.07. An index of movement harmonicity (Guiard in Acta Psychol 82:139-159, 1993) revealed that the repetitive aiming action was harmonic in nature when task ID was 3.07, and consisted of a series of discrete segments when task ID was 5.91. This finding provides evidence for the existence of discrete and cyclical units of action that are irreducible and that may be employed independently to assemble longer continuous actions. The scaling of ID within a trial promoted a transition in repetitive aiming motions assembled from discrete and cyclical units of action. A variety of kinematic measures (e.g., movement harmonicity, time spent accelerating the limb) revealed a critical ID (ID(c)) region (4.01-4.91) separating aiming motions governed by the different units of action. Enhancement of fluctuations before the transition were found in the movement harmonicity data and in the distance traveled to peak velocity data, with variability in these measures highest in the ID(c) region. The enhancement of fluctuations indicates that loss of stability in the limb's motion acted as a key mechanism underlying the transition between units of action. The loss of stability was associated with the transition from cyclical to discrete actions and with the transition from discrete to cyclical actions. The transition between units of action may be conceptualized as a transition from a limit cycle attractor (cyclical unit of action) to a shift between two fixed-point attractors (discrete unit of action) when ID was increased, with the transition occurring in the opposite direction when ID was decreased.}, } @article {pmid16914047, year = {2006}, author = {Ridolfi, R and Petrini, M and Fiammenghi, L and Stefanelli, M and Ridolfi, L and Ballardini, M and Migliori, G and Riccobon, A}, title = {Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients.}, journal = {Journal of translational medicine}, volume = {4}, number = {}, pages = {36}, pmid = {16914047}, issn = {1479-5876}, abstract = {BACKGROUND: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma.

METHODS: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 microg/ml of autologous-tumor-lysate (ATL) or -homogenate (ATH) and 50 microg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC) (range 4.5-82 x 10(6)) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 x 10(6)). Subcutaneous interleukin-2 (3 x 10(6) IU) was administered from days 3 to 7 of each treatment cycle.

RESULTS: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SD (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3-45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%).

CONCLUSION: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.}, } @article {pmid16911908, year = {2006}, author = {Kushner, JD and Nauman, D and Burgess, D and Ludwigsen, S and Parks, SB and Pantely, G and Burkett, E and Hershberger, RE}, title = {Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {12}, number = {6}, pages = {422-429}, doi = {10.1016/j.cardfail.2006.03.009}, pmid = {16911908}, issn = {1532-8414}, support = {5 M01 RR000334/RR/NCRR NIH HHS/United States ; R01-HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*genetics/physiopathology/surgery ; Cardiovascular System/*physiopathology ; Child ; Child, Preschool ; Death ; Female ; Heart Transplantation ; Humans ; Infant ; Male ; Medical Records ; Middle Aged ; Pedigree ; Time Factors ; }, abstract = {BACKGROUND: Familial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of unknown cause occurring in 2 or more closely related family members.

METHODS AND RESULTS: Members of 304 families suspected to have FDC were evaluated by family history (FH) and medical record review and were categorized as affected with idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data. Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC based on strength of evidence. Of the 304 pedigrees, 125 were categorized as confirmed FDC, 48 were probable FDC, 72 were possible FDC, and 59 had sporadic, nonfamilial IDC. Numbers of living first- and second-degree family members, and median number of relatives available for FH was greatest with confirmed FDC, and diminished for probable and possible FDC, and IDC categories. LV dimensions increased and LV function worsened in index patients along the spectrum from confirmed FDC, probable FDC, possible FDC and IDC, and a greater proportion of IDC patients underwent heart transplant. However, the age of onset, duration of disease, the time to death or heart transplant, and most other findings were similar among the 4 categories.

CONCLUSION: Clinical characteristics of IDC and FDC are similar, precluding an FDC diagnosis from clinical features only.}, } @article {pmid16904443, year = {2006}, author = {Monoski, MA and Gonzalez, RR and Sandhu, JS and Reddy, B and Te, AE}, title = {Urodynamic predictors of outcomes with photoselective laser vaporization prostatectomy in patients with benign prostatic hyperplasia and preoperative retention.}, journal = {Urology}, volume = {68}, number = {2}, pages = {312-317}, doi = {10.1016/j.urology.2006.02.020}, pmid = {16904443}, issn = {1527-9995}, mesh = {Humans ; *Laser Therapy ; Male ; Prostatectomy/*methods ; Prostatic Hyperplasia/complications/*physiopathology/*surgery ; Retrospective Studies ; Treatment Outcome ; Urinary Retention/etiology/*physiopathology/*surgery ; *Urodynamics ; }, abstract = {OBJECTIVES: To determine whether preoperative urodynamic parameters can predict the outcome in men in urinary retention and aid in counseling these men.

METHODS: Forty men in urinary retention due to benign prostatic hyperplasia underwent photoselective laser vaporization prostatectomy (PVP). Preoperative urodynamic studies were used to identify the men with detrusor overactivity (DO) and impaired detrusor contractility (IDC). The International Prostate Symptom Score (IPSS), maximal flow rate, and postvoid residual urine volume were collected at 1, 3, 6, and 12 months after PVP.

RESULTS: Of the 40 men, 8 (20%) had IDC and 30 had DO (75%) preoperatively. The men without preoperative DO had a significantly lower IPSS than those with preoperative DO at 1 month of follow-up. Men without preoperative IDC had a significantly lower IPSS and postvoid residual urine volume at the same point compared with men with preoperative IDC. The flow rate in men with preoperative IDC 1 and 6 months postoperatively was significantly lower than in men without preoperative IDC.

CONCLUSIONS: Preoperative urodynamic parameters predict for outcome in men in urinary retention undergoing PVP. Men in urinary retention benefit from PVP with an improvement in both subjective and objective voiding function, regardless of the presence of DO or IDC. Postoperatively, patients with DO have more voiding symptoms than those without DO, and are almost twice as likely to require anticholinergics. Men without IDC have better IPSS, flow rates, and postvoid residual urine volumes compared with men with IDC. Of the 8 men with IDC, 3 required reoperation within the first year.}, } @article {pmid16904381, year = {2006}, author = {Yang, S and Li, W and Liu, W and Gao, C and Zhou, B and Li, S and Li, Y and Kong, Y}, title = {IL-10 gene modified dendritic cells induced antigen-specific tolerance in experimental autoimmune myocarditis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {121}, number = {1}, pages = {63-73}, doi = {10.1016/j.clim.2006.06.009}, pmid = {16904381}, issn = {1521-6616}, mesh = {Adoptive Transfer ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*genetics/therapy ; Bone Marrow Cells/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism/transplantation ; Disease Models, Animal ; Epitopes/*immunology ; Immune Tolerance/*genetics ; Interleukin-10/*genetics/physiology ; Male ; Myocarditis/*genetics/*immunology/therapy ; Rats ; Rats, Inbred Lew ; }, abstract = {Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder, and the involvement of Th1/Th2 unbalance has been demonstrated. The induction of antigen-specific tolerance is critical for the treatment of EAM and maintenance of immune tolerance. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to explore the effects of IL-10 gene modified bone-marrow-derived immature dendritic cells (iDCs) on the in vitro and in vivo immune response to cardiac myosin in EAM. EAM was induced using the classic methods of cardiac myosin immunization on day 0 and day 7. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously for treatment 5 days after the first immunization. On day 21, transthoracic echocardiogram and HE staining were performed to detect the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen-specific tolerance induced by IL-10 gene modified iDCs. IL-10 gene modified iDC-treated EAM rats showed improved cardiac function and reduced infiltration of inflammatory cell into myocardium. Serum cytokines data indicated lower Th1 while higher Th2-type responses were induced in the pcDNA3-IL-10-iDC-treated group, suggesting a Th2 polarization. Moreover, IL-10 gene modified iDCs down-regulated MHC-II and costimulatory molecules on the surface of splenocytes and inhibited the antigen-specific immunological responses towards cardiac myosin. Adoptive transfer of IL-10 producing DCs prevented EAM induction. IL-10 gene modified iDCs ameliorates EAM histopathologically and functionally. The underlying mechanisms may be related to the IL-10 induced Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecules expression.}, } @article {pmid16901685, year = {2007}, author = {Schlecht, U and Malavé, A and Gronewold, TM and Tewes, M and Löhndorf, M}, title = {Detection of Rev peptides with impedance-sensors--comparison of device-geometries.}, journal = {Biosensors & bioelectronics}, volume = {22}, number = {9-10}, pages = {2337-2340}, doi = {10.1016/j.bios.2006.06.034}, pmid = {16901685}, issn = {0956-5663}, mesh = {*Biosensing Techniques ; Electric Impedance ; Gene Products, rev/*isolation & purification ; Peptides/*isolation & purification ; }, abstract = {Two different impedance-sensor geometries have been compared for the detection of Rev peptides with a molecular weight of 2.4 kDa. Planar, two-dimensional interdigitated capacitor (IDC) sensors with electrode separations of 1.1 microm as well as three-dimensional nanogap-sensors with an electrode separation of 75 nm have been used. Both sensors have been operated at a fixed frequency of 980 MHz. We discuss the specific interaction of the Rev peptide to an immobilized RNA anti-Rev aptamer (9.2 kDa) for peptide concentrations in the range of 100 nM-2 microM. For the IDC sensor, only peptide concentrations above 500 nM gave detectable signals. For the nanogap sensor, the binding process was clearly visible for all concentrations applied. The higher sensitivity of the nanogap compared to the IDC is ascribed to the improved surface-to-volume ratio.}, } @article {pmid16888913, year = {2003}, author = {Diallo, R and Tognon, C and Knezevich, SR and Sorensen, P and Poremba, C}, title = {Secretory carcinoma of the breast: a genetically defined carcinoma entity.}, journal = {Verhandlungen der Deutschen Gesellschaft fur Pathologie}, volume = {87}, number = {}, pages = {193-203}, pmid = {16888913}, issn = {0070-4113}, mesh = {3T3 Cells ; Adult ; Aged ; Animals ; Breast Neoplasms/classification/*genetics/*pathology ; Child ; Female ; Gene Fusion ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; Middle Aged ; Nucleic Acid Hybridization ; Proto-Oncogene Proteins c-ets/genetics ; Receptor, trkC/genetics ; Repressor Proteins/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; }, abstract = {Secretory carcinomas (SBC) are characterized by their characteristic histomorphology and more favorable prognosis compared to invasive ductal carcinoma of usual type (IDC). On this basis, 13 SBCs are evaluated by molecular and immunohistochemical (IH) methods. 13 SBCs and 4 IDCs were analyzed for ETV6-NTRK3 gene fusion by reverse transcriptase-polymerase chain reaction (RT-PCR) and by Fluorescence in situ Hybridization (FISH). 8 of 13 microdissected SBCs with evaluable DNA were evaluated for genetic alterations (GA) by comparative genomic hybridization (CGH). IH included estrogen-receptor (ER), progesterone-receptor (PR), Her-2/neu and Ki-67 (MIB-1) in all 13 cases. Molecular and immunohistochemical results in SBCs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. 12 of 13 (92 %) SBC cases, but not IDCs expressed the ETV6-NTRK3 fusion gene which encodes a chimeric tyrosine kinase. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed epithelial tumors in nude mice. CGH revealed an average of 2.0 GAs (range 0-6), including recurrent gains of chromosome 8q and 1q and losses of 22q. Four SBCs were positive for ER and 2 were positive for PR. The mean MIB-1-labeling index was 11.4% (range: <1-34%). Her-2/ neu protein overexpression was detected in 1 case (score 3+). Compared to previous findings in IDCs, SBCs are characterized by the recurrent expression of ETV6-NTRK3 fusion gene, a relatively low number of GAs, low proliferative rate, infrequent Her-2/ neu protein overexpression and a lower rate of steroid hormone receptor expression. These results support the hypothesis that SBCs have immunohistochemical and genetic features that specifically distinguish them from IDCs.}, } @article {pmid16886641, year = {2006}, author = {Okada, T and Masuda, N and Fukai, Y and Shimura, T and Nishida, Y and Hosouchi, Y and Kashiwabara, K and Nakajima, T and Kuwano, H}, title = {Immunohistochemical expression of 14-3-3 sigma protein in intraductal papillary-mucinous tumor and invasive ductal carcinoma of the pancreas.}, journal = {Anticancer research}, volume = {26}, number = {4B}, pages = {3105-3110}, pmid = {16886641}, issn = {0250-7005}, mesh = {14-3-3 Proteins ; Adenocarcinoma, Mucinous/*metabolism/pathology ; Biomarkers, Tumor/*biosynthesis ; Carcinoma, Pancreatic Ductal/*metabolism/pathology ; Carcinoma, Papillary/*metabolism/pathology ; Exonucleases/*biosynthesis ; Exoribonucleases ; Humans ; Immunohistochemistry ; Neoplasm Proteins/*biosynthesis ; Pancreatic Neoplasms/*metabolism/pathology ; }, abstract = {BACKGROUND: 14-3-3 sigma (sigma) has been shown to be overexpressed in pancreatic cancers by a c-DNA microarray technique. However, the expression of 14-3-3 sigma in intraductal papillary-mucinous tumor (IPMT) of the pancreas remains unclear.

MATERIALS AND METHODS: To evaluate the biological importance of 14-3-3 sigma expression in pancreatic carcinogenesis, immunohistochemistry for 14-3-3 sigma, CDX2, MUC1, MUC2, p53, p16 and Ki-67 was carried out on 33 IPMTs and the results were compared with those for 14 invasive ductal carcinomas (IDCs).

RESULTS: The frequency of 14-3-3 sigma immunoreactivity was 70% and 100% in IPMT and IDC, respectively. The frequency of MUCI and Ki-67 immunoreactivity was significantly higher in IDC than IPMT. In IPMT, dark columnar cell types prevailed over clear columnar cell types in terms of the frequency of the Ki-67 labeling index.

CONCLUSION: The overexpression of 14-3-3 sigma was confirmed in both IDC and IPMT. Therefore, this overexpression might occur in the early stages of pancreatic carcinogenesis. Moreover, IPMT composed of dark columnar cells might be a potentially more advanced form than that made up of clear columnar cells.}, } @article {pmid16882710, year = {2006}, author = {Krispin, A and Bledi, Y and Atallah, M and Trahtemberg, U and Verbovetski, I and Nahari, E and Zelig, O and Linial, M and Mevorach, D}, title = {Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states.}, journal = {Blood}, volume = {108}, number = {10}, pages = {3580-3589}, doi = {10.1182/blood-2006-03-013334}, pmid = {16882710}, issn = {0006-4971}, mesh = {Antigens, CD/physiology ; Apoptosis/*immunology ; Binding Sites ; Dendritic Cells/*physiology ; Gene Expression Regulation ; Heparin ; Humans ; *Immune Tolerance ; Monocytes/cytology/*metabolism ; *Phagocytosis ; Proteomics/methods ; Thrombospondin 1/*biosynthesis/isolation & purification/metabolism ; }, abstract = {Apoptotic cells were shown to induce dendritic cell immune tolerance. We applied a proteomic approach to identify molecules that are secreted from apoptotic monocytes, and thus may mediate engulfment and immune suppression. Supernatants of monocytes undergoing apoptosis were collected and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and differentially expressed proteins were identified using tandem mass spectrometry. Thrombospondin-1 (TSP-1) and its cleaved 26-kDa heparin-binding domain (HBD) were identified. We show that TSP-1 is expressed upon induction of monocyte apoptosis in a caspase-dependent pattern and the HBD is cleaved by chymotrypsin-like serine protease. We further show that CD29, CD36, CD47, CD51, and CD91 simultaneously participate in engulfment induction and generation of an immature dendritic cell (iDC) tolerogenic and phagocytic state. We conclude that apoptotic cell TSP-1, and notably its HBD, creates a signalosome in iDCs to improve engulfment and to tolerate engulfed material prior to the interaction with apoptotic cells.}, } @article {pmid16878410, year = {2006}, author = {Fujii, Y and Ueda, M and Yoshida, K and Matsuo, K and Takeda, K and Morioka, D and Tanaka, K and Endo, I and Togo, S and Shimada, H}, title = {[Standard surgery as part of the multidisciplinary treatment for pancreatic cancer].}, journal = {Nihon Geka Gakkai zasshi}, volume = {107}, number = {4}, pages = {177-181}, pmid = {16878410}, issn = {0301-4894}, mesh = {Carcinoma, Ductal/mortality/pathology/*surgery ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Male ; Myenteric Plexus/surgery ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatectomy/methods/*standards/trends ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Portal Vein/surgery ; Survival Rate ; }, abstract = {Standardization of surgical procedure for pancreatic cancer has been recognized to be necessary and important these days. Recent studies appear to exhibit efficacy of the adjuvant chemoradiation therapy before or after pancreatic surgery. In this study, we examined the standard surgery as part of the multidisciplinary treatment for pancreatic cancer. Invasive ductal carcinoma of the pancreas was resected in 121 patients in our institution from 1992 through 2005. We stopped performing an extended lymphadenectomy with pancreatectomy in 2003, but the survival rates were not significantly different between the cases before and after 2003. We usually resect half of the nerve plexus around the superior mesenteric artery (SMA) as a standard procedure. When we achieved the microscopically curative resection (R0) even if the plexus around SMA or the portal vein was invaded, there were a few long survivors for more than five years. The R0 resection is the most important factor for prolonged survival. Pancreatectomy including removal of regional lymph nodes (D2) and half of the nerve plexus around SMA and combined resection of the infiltrated portal vein is thought to be a standard surgery from the viewpoint of decrease in morbidity and maintenance of curability.}, } @article {pmid16878408, year = {2006}, author = {Doi, R and Kami, K and Ito, D and Kawaguchi, Y and Uemoto, S and Yoshida, S}, title = {[Surgical treatment of carcinoma of the pancreas].}, journal = {Nihon Geka Gakkai zasshi}, volume = {107}, number = {4}, pages = {168-172}, pmid = {16878408}, issn = {0301-4894}, mesh = {Carcinoma, Ductal/mortality/pathology/*surgery ; Combined Modality Therapy ; Humans ; Neoplasm Staging ; *Pancreatectomy/methods ; Pancreatic Neoplasms/mortality/pathology/*surgery ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Survival Rate ; }, abstract = {Invasive ductal carcinoma of the pancreas (pancreatic cancer) is mainly treated by operative resection, radio-chemotherapy, or chemotherapy. The survival rate of the patients with each treatment is not good when compared with that in other cancers. Meanwhile, it is still true that surgical resection remains the only method offering pancreatic cancer patients long-term survival or cure. The indications for surgical resection should be considered based on whether margin-free resection can be achieved in individual patients. In addition, the volume of pancreatic cancer patients treated at the institution and the surgeon's personal experience may greatly affect the decision. A recent randomized clinical trial from Japan revealed that surgical resection has a survival advantage over chemo-radiation therapy for locally advanced pancreatic cancer, which is defined as stage IVa in the fourth Japanese edition of the Classification of Pancreatic Carcinoma. Moreover, guidelines for clinical practice for pancreatic cancer by the Japan Pancreas Society have been issued very recently. In addition, the surgical indications should be reevaluated in combination with the adjuvant or neoadjuvant chemotherapy in future.}, } @article {pmid16875603, year = {2006}, author = {Tang, F and Gu, DH and Wang, H and Zhu, TF and Zhu, HG and Xu, ZD and Hu, XQ}, title = {[Expression and significance of hTERT mRNA in breast carcinoma and its relation to p53].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {28}, number = {3}, pages = {192-195}, pmid = {16875603}, issn = {0253-3766}, mesh = {Adult ; Breast/metabolism/pathology ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Diagnosis, Differential ; Disease Progression ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger/biosynthesis/genetics ; Telomerase/*biosynthesis/genetics ; Tumor Suppressor Protein p53 ; }, abstract = {OBJECTIVE: This study was designed to investigate the significance of hTERT mRNA in breast carcinogenesis and to explore the diagnostic efficacy, and to study the effect of tumor suppressor gene p53 on the expression of hTERT mRNA.

METHODS: The expression of hTERT mRNA was examined by in situ hybridization in 12 cases of normal breast tissue nearby cancer, 7 of simple ductal hyperplasia, 20 of atypical hyperplasia, 18 of ductal carcinoma in situ and 25 with invasive ductal carcinoma. The expression of p53 protein were examined by immunohistochemistry in 43 carcinomas.

RESULTS: hTERT was not detected in normal breast tissue nearby cancer and simple ductal hyperplasia. The positive rate of hTERT mRNA in atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma were 25.0%, 83.3% and 88.0%, respectively. The prevalence and intensity of hTERT mRNA expression were much greater in carcinoma than those in simple or atypical hyperplasia and normal breast tissue nearby cancer (P < 0.05). The expression of hTERT was not correlated with tumor size and lymph node metastasis (P > 0.05). The positive correlation between hTERT mRNA and p53 was found in breast carcinoma (r = 0.5540, P < 0.01).

CONCLUSION: hTERT mRNA expression is closely related to the malignant transformation of breast tissue. Semi-quantitative detection of hTERT mRNA expression in situ is helpful in differentiated diagnosis of carcinoma in situ and atypical hyperplasia. Inactivation of p53 may play a role in the transcriptive activation of hTERT gene in breast carcinoma.}, } @article {pmid16875423, year = {2006}, author = {Ivković-Kapicl, T and Knelević-Usaj, S and Panjković, M and Mastilović, K}, title = {[Immunohistochemical analysis of angiogenesis in invasive ductal breast carcinoma with correlations to clinicopathological factor].}, journal = {Vojnosanitetski pregled}, volume = {63}, number = {7}, pages = {635-642}, doi = {10.2298/vsp0607635i}, pmid = {16875423}, issn = {0042-8450}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood supply/chemistry/pathology ; Carcinoma, Ductal, Breast/*blood supply/chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neovascularization, Pathologic/*pathology ; }, abstract = {BACKGROUND/AIM: Angiogenesis is the formation of new vessels from preexisting ones. The aim of our study was to determine the relevance of tumor-induced angiogenesis, its correlation with some of the commonly used clinical, pathological factors and the recent biological indicators, and metastatic potential of the tumor in a series of 120 patients with invasive ductal carcinoma of the breast.

METHODS: The identification of microvessels was performed immunohistochemically with factor VIII-related antigen. The microvessel count (MVC) was assessed at the invasive front of each carcinoma. The cases were divided into high-and low-microvessel density groups according to an average number of microvessels found in the multiple fields of the most vessel-dense part of each tumor. The nuclear immunohistochemical staining for hormone receptors, and the p53, and the membranous staining for c-erbB-2 were evalueted.

RESULTS: There were significant correlations between a high MVC and a large tumor size, high histological grade, and c-erbB-2 protein overexpression. There was no association between tumor angiogenesis, as assessed by the MVC, and the hormone receptors status, and the p53 protein expression. In the cases with a high MVC, there was a significant number of tumors with lymph node metastases.

CONCLUSION: Our findings showed that a high MVC might point out an aggressive tumor phenotype. This might help to stratify patients for an appropriate therapy on an individual basis and, thus, offer the possibility of a more effectively tailored treatment program.}, } @article {pmid16872435, year = {2006}, author = {Umekita, Y and Souda, M and Ohi, Y and Sagara, Y and Rai, Y and Takahama, T and Yoshida, H}, title = {Expression of wild-type estrogen receptor beta protein in human breast cancer: specific correlation with HER2/neu overexpression.}, journal = {Pathology international}, volume = {56}, number = {8}, pages = {423-427}, doi = {10.1111/j.1440-1827.2006.01983.x}, pmid = {16872435}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/secondary/surgery ; Cell Nucleus/metabolism/pathology ; Estrogen Receptor beta/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Mammary Glands, Human/metabolism ; Middle Aged ; Neoplasm Staging ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/*metabolism ; Receptors, Progesterone/metabolism ; Trastuzumab ; }, abstract = {Expression of estrogen receptor beta (ERbeta) protein in human breast cancer and correlation with clinicopathological factors have been reported by many investigators, but many of them used ERbeta antibodies that react with both wild-type ERbeta (ERbetawt) and splicing variant isoform. Therefore, the frequency and correlation with clinicopathological factors of ERbetawt expression remain to be established. In the present study a monoclonal antibody EMR02, specific for ERbetawt, was used in formalin-fixed paraffin-embedded sections from 225 female primary breast cancer patients diagnosed as having invasive ductal carcinoma. Expression of ERalpha, progesterone receptor (PgR) and HER2/neu were also investigated by immunohistochemistry. For ERbetawt, ERalpha and PgR, positivity was defined as nuclear staining in >10% of the cancer cells. HER2/neu overexpression was defined as a Hercep test score 3+. Positivity for ERbetawt, ERalpha, PgR and HER2/neu overexpression was 55%, 74%, 61% and 25%, respectively. The expression of ERbetawt had a positive correlation with ERalpha (P=0.018) and PgR (P=0.02). There was significant positive correlation between ERbetawt expression and HER2/neu overexpression (P<0.0001). According to multivariate logistic regression analysis the most significant association was between ERbetawt expression and HER2/neu overexpression (P<0.0001). These results suggest that clinical significances of ERbetawt expression in human breast cancer patients may be more complex.}, } @article {pmid16861974, year = {2006}, author = {Weinreb, I and Tabanda-Lichauco, R and Van der Kwast, T and Perez-Ordoñez, B}, title = {Low-grade intraductal carcinoma of salivary gland: report of 3 cases with marked apocrine differentiation.}, journal = {The American journal of surgical pathology}, volume = {30}, number = {8}, pages = {1014-1021}, doi = {10.1097/00000478-200608000-00013}, pmid = {16861974}, issn = {0147-5185}, mesh = {Aged ; Apocrine Glands/*pathology ; Biomarkers, Tumor/analysis ; Carcinoma, Ductal/*metabolism/*pathology ; Carcinoma, Squamous Cell/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasms, Multiple Primary/pathology ; Salivary Gland Neoplasms/*metabolism/*pathology ; }, abstract = {Low-grade intraductal carcinomas (LG-IDCs) of salivary gland are rare neoplasms that resemble atypical ductal hyperplasia or LG-IDCs of the breast. They have been referred to as "low-grade salivary duct carcinomas" or "low-grade cribriform cystadenocarcinomas." Herein, we describe 3 additional cases of LG-IDCs, 2 were pure intraductal carcinomas, although 1 demonstrated increasing cytologic atypia and progression to an invasive adenosquamous carcinoma. The latter had been present for 7 years before demonstrating clinical and pathologic progression to a widely invasive malignancy. The intraductal component in all cases exhibited a remarkable degree of apocrine differentiation. The tumor cells were positive for AE1:AE3, Cam 5.2, high molecular weight keratin, CK7, CK19, BRST-2, and androgen receptors (ARs). S-100 was positive in 2 cases and negative in 1 case. The intraductal neoplastic cells were surrounded by myoepithelial cells positive for CK14, actins, calponin, high molecular weight keratin, and p63. All the tumors were negative for CK20, estrogen and progesterone receptors, Her2Neu, and p53. Extensive apocrine differentiation, expression of ARs, CK7, and CK19, and progression to a widely invasive carcinoma after a long clinical latency have not been reported in LG-IDCs previously. These tumors share some histopathologic features with salivary duct carcinoma including apocrine differentiation, and expression of ARs and BRST-2. The terms "low-grade salivary duct carcinomas" and "low-grade cribriform cystadenocarcinomas" should be abandoned in favor of LG-IDC of salivary gland, which better reflects their predominantly noninvasive, intraductal nature.}, } @article {pmid16861530, year = {2006}, author = {Narisada, H and Aoki, T and Sasaguri, T and Hashimoto, H and Konishi, T and Morita, M and Korogi, Y}, title = {Correlation between numeric gadolinium-enhanced dynamic MRI ratios and prognostic factors and histologic type of breast carcinoma.}, journal = {AJR. American journal of roentgenology}, volume = {187}, number = {2}, pages = {297-306}, doi = {10.2214/AJR.05.0696}, pmid = {16861530}, issn = {1546-3141}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; *Contrast Media ; Female ; *Gadolinium ; Humans ; Magnetic Resonance Imaging/*methods/statistics & numerical data ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVE: The purpose of this study was to assess the usefulness of numeric ratios from dynamic contrast-enhanced MRI in predicting histologic type of breast carcinoma and three histologic prognostic factors for invasive ductal carcinoma.

MATERIALS AND METHODS: A total of 104 patients with breast carcinoma were included in the study. Dynamic contrast-enhanced MR images were obtained every 30 seconds during the first 4.5 minutes after administration of contrast material, and peripheral contrast enhancement ratio and central contrast enhancement ratio were calculated in the early phase (1 minute after contract injection) and in the delayed phase (4 minutes after injection). Four contrast enhancement ratios were used for quantitative analysis of the following numeric ratios: early peripheral/early central, delayed peripheral/delayed central, delayed peripheral/early peripheral, and delayed central/early central. The four ratios were compared with histologic type. For invasive ductal carcinoma, the ratios were then compared with modified Scarff-Bloom-Richardson histologic grade, microvessel density, and fibrotic focus.

RESULTS: Mucinous carcinoma had significantly higher mean early peripheral/early central and delayed central/early central ratios than other types of tumors (p< 0.0001). For invasive ductal carcinoma, the mean early peripheral/early central ratio was significantly lower for modified Scarff-Bloom-Richardson grade 1 tumors than for grades 2 and 3 tumors (p < 0.0001). Early peripheral/early central ratio had a significant correlation with the ratio of peripheral to central mean microvessel density (p < 0.0001). There was also a significant difference in early peripheral/early central ratio (p < 0.0001) between tumors with a fibrotic focus and those without a fibrotic focus.

CONCLUSION: Numeric ratios obtained on gadolinium-enhanced dynamic MRI of the breast may be useful in predicting histologic type of breast carcinoma and three histologic prognostic factors for invasive ductal carcinoma: modified Scarff-Bloom-Richardson grade, microvessel density, and fibrotic focus.}, } @article {pmid16858545, year = {2006}, author = {Nishikawa, N and Kimura, Y and Okita, K and Zembutsu, H and Furuhata, T and Katsuramaki, T and Kimura, S and Asanuma, H and Hirata, K}, title = {Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {13}, number = {4}, pages = {327-335}, doi = {10.1007/s00534-005-1073-1}, pmid = {16858545}, issn = {0944-1166}, mesh = {Adenocarcinoma, Mucinous/metabolism/surgery ; Adenocarcinoma, Papillary/metabolism/surgery ; Adult ; Aged ; Aged, 80 and over ; Cadherins/*metabolism ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/surgery ; Disease-Free Survival ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 7/*metabolism ; Middle Aged ; Pancreatic Neoplasms/*metabolism/mortality/surgery ; Prognosis ; Proliferating Cell Nuclear Antigen/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {BACKGROUND/PURPOSE: The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs.

METHODS: Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded.

RESULTS: Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05).

CONCLUSIONS: Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.}, } @article {pmid16855320, year = {2006}, author = {Khanna, AK}, title = {Pharmaceutical industry's corporate social responsibility towards HIV/AIDS.}, journal = {Journal of postgraduate medicine}, volume = {52}, number = {3}, pages = {194-196}, pmid = {16855320}, issn = {0022-3859}, mesh = {Acquired Immunodeficiency Syndrome/*drug therapy ; *Anti-HIV Agents/administration & dosage/economics ; Chemistry, Pharmaceutical ; Developing Countries ; Dosage Forms ; Drug Combinations ; Drug Costs ; *Drug Industry ; Health Services Accessibility ; Humans ; Patient Compliance ; *Social Responsibility ; }, abstract = {The pharmaceutical industry has a corporate social responsibility (CSR) towards HIV/AIDS. Measures taken to increase awareness of HIV/AIDS, availability and accessibility of potent and patient-friendly FDCs / Kits for adults and children will go a long way in increasing awareness and acceptance of this disease and its therapy. This will improve adherence, lower resistance and facilitate better disease management. This article discusses some of the CSR initiatives and their scope.}, } @article {pmid16850685, year = {2006}, author = {Wiratkapun, C and Wibulpolprasert, B and Lertsithichai, P}, title = {Breast cancer in patients initially assigned as BI-RADS category 3.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {89}, number = {6}, pages = {834-839}, pmid = {16850685}, issn = {0125-2208}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Disease Progression ; Female ; Hospitals, University ; Humans ; Mammography ; Middle Aged ; Neoplasm Staging ; Population Surveillance ; Predictive Value of Tests ; Retrospective Studies ; Time Factors ; Ultrasonography ; }, abstract = {OBJECTIVES: To determine the Positive Predictive Value (PPV) for malignancy and characteristics of breast cancer found in patients who were initially categorized as having Breast Imaging Reporting and Data System (BI-RADS) 3.

MATERIAL AND METHOD: Medical records of patients assigned to BI-RADS 3 from January, 1st to December; 31st 2002 at the Breast diagnostic center, Ramathibodi Hospital who had imaging follow-up for at least 2 years or had biopsy performed were retrospectively reviewed

RESULTS: Of 949 patients, 23 were found to have malignancy, i.e., 2.4% PPV. The most common imaging findings of breast cancer were calcifications on mammogram and mass on sonogram. Mean interval from first imaging to biopsy was 13.1 months. Only 78% of malignancies were diagnosed within 2 years. Less than 50% of these were ductal carcinoma in situ or stage I invasive ductal carcinoma.

CONCLUSION: PPV for malignancy in the present study was comparable to the previous studies. However, longer time to diagnosis and more advanced stage of breast cancer at diagnosis were found Periodically short-interval mammogram and sonogram, at not less than 2 year-intervals, were recommended}, } @article {pmid16848850, year = {2006}, author = {Ruiz-Tovar, J and Reguero-Callejas, ME and Aláez, AB and Ramiro, C and Rojo, R and Collado, MV and González-Palacios, F and Muñoz, J and García-Villanueva, A}, title = {Infiltrating ductal carcinoma and ductal carcinoma in situ associated with mammary hamartoma.}, journal = {The breast journal}, volume = {12}, number = {4}, pages = {368-370}, doi = {10.1111/j.1075-122X.2006.00279.x}, pmid = {16848850}, issn = {1075-122X}, mesh = {Adult ; Breast Diseases/*complications/pathology/surgery ; Breast Neoplasms/*complications/pathology/surgery ; Carcinoma, Ductal, Breast/*complications/pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*complications/pathology/surgery ; Female ; Hamartoma/*complications/pathology/surgery ; Humans ; Mastectomy ; }, abstract = {Mammary hamartoma is a rare nonmalignant lesion. Only 11 cases of carcinoma associated with hamartoma have been previously described in the literature. We describe a case of infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) associated with hamartoma in a 35-year-old woman. Mammography showed the features of a typical hamartoma with suspicious microcalcifications arising in it. The patient underwent a radical modified mastectomy. It is likely that hamartoma is a coincidental finding. The identification of suspicious microcalcifications in a typical mammographic image of a hamartoma should prompt continued examination to exclude an underlying tumor.}, } @article {pmid16848839, year = {2006}, author = {Killebrew, LK and Oneson, RH}, title = {Comparison of the diagnostic accuracy of a vacuum-assisted percutaneous intact specimen sampling device to a vacuum-assisted core needle sampling device for breast biopsy: initial experience.}, journal = {The breast journal}, volume = {12}, number = {4}, pages = {302-308}, doi = {10.1111/j.1075-122X.2006.00268.x}, pmid = {16848839}, issn = {1075-122X}, mesh = {Biopsy/adverse effects/*instrumentation ; Biopsy, Needle/instrumentation ; Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Predictive Value of Tests ; Retrospective Studies ; Specimen Handling ; Vacuum ; }, abstract = {The objective of this research was to determine whether biopsy of the breast using a percutaneous intact specimen sampling device influences the underestimation rate of ductal carcinoma in situ (DCIS) compared to a vacuum-assisted core needle biopsy (VACNB) device. This study was a retrospective comparison of two series of 800 consecutive patients that underwent stereotactic biopsy of the breast for mammographic lesions presenting as microcalcifications classified by our institution as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5. In the first series of patients (n = 800), a VACNB device was used; in the second series (n = 800), a vacuum-assisted percutaneous intact specimen biopsy (VAPIB) device was used. Initial diagnoses were made from the histopathologic examination of the tissue retrieved at biopsy. Lesions presenting as DCIS or atypical ductal hyperplasia (ADH) after percutaneous biopsy were then compared to the histopathologic analysis of specimens retrieved at surgical biopsy. DCIS upgrades were defined as cases in which the diagnosis of the stereotactic biopsy was DCIS and the diagnosis of the subsequent surgical excision was infiltrating ductal carcinoma (IDC). ADH upgrades were defined as cases in which the diagnosis of the stereotactic biopsy specimen was ADH and the diagnosis of the surgical excision was DCIS, lobular carcinoma in situ (LCIS), or IDC. The lesions retrieved by both biopsy techniques yielded a similar pathology distribution. Underestimation of DCIS occurred less frequently (p = 0.06) in the biopsy samples taken using the intact biopsy device (1/31, 3.2%) as compared to biopsy samples taken using the core needle biopsy device (7/36, 19.4%). No significant adverse events were reported. Breast biopsy can be performed safely and accurately using a vacuum-assisted percutaneous intact specimen sampling device. In this study, such a device trended toward fewer underestimations of DCIS at biopsy compared to the vacuum-assisted core needle sampling biopsy method.}, } @article {pmid16847919, year = {2006}, author = {Dinshaw, KA and Sarin, R and Budrukkar, AN and Shrivastava, SK and Deshpande, DD and Chinoy, RF and Badwe, R and Hawaldar, R}, title = {Safety and feasibility of breast conserving therapy in Indian women: two decades of experience at Tata Memorial Hospital.}, journal = {Journal of surgical oncology}, volume = {94}, number = {2}, pages = {105-113}, doi = {10.1002/jso.20497}, pmid = {16847919}, issn = {0022-4790}, mesh = {Adolescent ; Adult ; Aged ; Axilla ; Breast Neoplasms/mortality/pathology/*radiotherapy/*surgery ; Cohort Studies ; Combined Modality Therapy ; Dose Fractionation, Radiation ; Feasibility Studies ; Female ; Humans ; India/ethnology ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; *Mastectomy, Segmental/standards/statistics & numerical data ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE: The NIH consensus statement on the management of breast cancer has highlighted the paucity of outcome data in non-Caucasian women. Treatment outcome and factors determining it in a large cohort of ethnic Indian women treated with breast conserving therapy (BCT) at Tata Memorial Hospital are reported here.

MATERIALS AND METHODS: During 1980-2000, 1,022 pathological Stage I/II breast cancer patients (median age 43 years) underwent BCT (wide excision, complete axillary clearance, whole breast radiotherapy with 6 MV photons plus tumor bed boost, +/-systemic therapy). Median pathological tumor size was 3 cm (1-5 cm). Axillary node metastases were found in 39% women. Of the 938 patients with IDC, 70% were Grade III and in patients where receptor status was known, 209/625 (33%) were ER positive and 245/591 (41%) were PR positive.

RESULTS: The 5- and 10-year actuarial overall survival was 87% and 77% and disease-free survival was 76% and 68%, respectively. Actuarial 5-year local and locoregional control rates were 91% and 87%, respectively. Cosmesis was good or excellent in 78% women. Independent adverse prognostic factors for local recurrence were, age<40 years, axillary node metastasis, lymphovascular invasion (LVI), and adjuvant systemic therapy; for locoregional recurrence-inner quadrant tumor, axillary node metastasis, and LVI; for survival-LVI and axillary node metastasis.

CONCLUSION: Compared to Caucasians, these Indian women undergoing BCT were younger, had larger, higher grade, and receptor negative tumors. Comparable local control and survival was obtained by using stringent quality assurance in the diagnostic and therapeutic protocol. BCT, a resource intense treatment is safe for selected and motivated patients undergoing treatment at centers with adequate facilities and expertise even in countries with limited resources.}, } @article {pmid16846989, year = {2006}, author = {Wood, CE and Usborne, AL and Starost, MF and Tarara, RP and Hill, LR and Wilkinson, LM and Geisinger, KR and Feiste, EA and Cline, JM}, title = {Hyperplastic and neoplastic lesions of the mammary gland in macaques.}, journal = {Veterinary pathology}, volume = {43}, number = {4}, pages = {471-483}, doi = {10.1354/vp.43-4-471}, pmid = {16846989}, issn = {0300-9858}, support = {AT00639/AT/NCCIH NIH HHS/United States ; P51RR000167/RR/NCRR NIH HHS/United States ; P51RR000169/RR/NCRR NIH HHS/United States ; T32 RR07009/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Carcinoma in Situ/genetics/metabolism/pathology/*veterinary ; Carcinoma, Ductal/genetics/metabolism/pathology/*veterinary ; Female ; Gene Expression ; Genes, erbB-2 ; Immunohistochemistry/veterinary ; Ki-67 Antigen/metabolism ; *Macaca fascicularis ; *Macaca mulatta ; Male ; Mammary Glands, Animal/metabolism/pathology ; Mammary Neoplasms, Animal/genetics/metabolism/*pathology ; Monkey Diseases/genetics/metabolism/*pathology ; Oncogenes ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Retrospective Studies ; }, abstract = {Macaques provide an important animal model for the study of hormonal agents and their effects on risk biomarkers for breast cancer. A common criticism of this model is that spontaneous breast cancer has rarely been described in these animals. In this report, we characterize 35 mammary gland lesions ranging from ductal hyperplasia to carcinoma in situ and invasive ductal carcinoma in cynomolgus and rhesus macaques. Based on a retrospective analysis, we estimated the lifetime incidence of mammary gland neoplasia in aged female macaques to be about 6%. Hyperplastic lesions (n = 19) occurred segmentally along ducts and included such features as columnar alteration, micropapillary atypia, and fibroadenomatous change. In situ carcinomas (n = 8) included solid, comedo, cribriform, and micropapillary elements, encompassing 4 of the major architectural patterns seen in human lesions. Invasive ductal carcinomas (n = 8) were generally solid, with prominent central necrosis and mineralization, often on a background of micropapillary ductal hyperplasia and in situ carcinoma. Cytologic changes of invasive lesions included increased mitoses, nuclear pleomorphism, extensive microinvasion, and stromal desmoplasia. Axillary lymph-node metastases were confirmed in 5 of the 8 invasive carcinomas. On immunohistochemistry, intraductal and invasive carcinomas had increased Ki67/MIB1 and HER2 expression and selective loss of estrogen and progesterone receptors. These findings suggest that breast cancer is an underreported lesion in macaques and highlight unique morphologic and molecular similarities in breast cancer between human and macaque species.}, } @article {pmid16846613, year = {2006}, author = {Marrero, A and Mallorquí-Fernández, G and Guevara, T and García-Castellanos, R and Gomis-Rüth, FX}, title = {Unbound and acylated structures of the MecR1 extracellular antibiotic-sensor domain provide insights into the signal-transduction system that triggers methicillin resistance.}, journal = {Journal of molecular biology}, volume = {361}, number = {3}, pages = {506-521}, doi = {10.1016/j.jmb.2006.06.046}, pmid = {16846613}, issn = {0022-2836}, mesh = {Acylation ; Amino Acid Sequence ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Methicillin/*pharmacology ; Methicillin Resistance/*physiology ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; Staphylococcus aureus/drug effects/*metabolism ; }, abstract = {Methicillin-resistant Staphylococcus aureus (MRSA) strains are responsible for most hospital-onset bacterial infections. Lately, they have become a major threat to the community through infections of skin, soft tissue and respiratory tract, and subsequent septicaemia or septic shock. MRSA strains are resistant to most beta-lactam antibiotics (BLAs) as a result of the biosynthesis of a penicillin-binding protein with low affinity for BLAs, called PBP2a, PBP2' or MecA. This response is regulated by the chromosomal mec-divergon, which encodes a signal-transduction system including a transcriptional repressor, MecI, and a sensor/transducer, MecR1, as well as the structural mecA gene. This system is similar to those encoded by bla divergons in S. aureus and Bacillus licheniformis. MecR1 comprises an integral-membrane latent metalloprotease domain facing the cytosol and an extracellular sensor domain. The latter binds BLAs and transmits a signal through the membrane that eventually triggers activation of the metalloprotease moiety, which in turn switches off MecI-induced repression of mecA transcription. The MecR1 sensor domain, MecR1-PBD, reveals a two-domain structure of alpha/beta-type fold reminiscent of penicillin-binding proteins and beta-lactamases, and a catalytic serine residue as the ultimate cause for BLA-binding. Covalent complexes with benzylpenicillin and oxacillin provide evidence that serine acylation does not entail significant structural changes, thus supporting the hypothesis that additional extracellular segments of MecR1 are involved in signal transmission. The chemical nature of the residues shaping the active-site cleft favours stabilisation of the acyl enzyme complexes in MecR1-PBD, in contrast to the closely related OXA beta-lactamases, where the cleft is more likely to promote subsequent hydrolysis. The present structural data provide insights into the mec-encoded BLA-response mechanism and an explanation for kinetic differences in signal transmission with the related bla-encoded systems.}, } @article {pmid16842243, year = {2006}, author = {Fulford, LG and Easton, DF and Reis-Filho, JS and Sofronis, A and Gillett, CE and Lakhani, SR and Hanby, A}, title = {Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast.}, journal = {Histopathology}, volume = {49}, number = {1}, pages = {22-34}, doi = {10.1111/j.1365-2559.2006.02453.x}, pmid = {16842243}, issn = {0309-0167}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/classification/metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Keratin-14 ; Keratins/metabolism ; Neoplasms, Basal Cell/classification/metabolism/pathology ; Phenotype ; }, abstract = {AIMS: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC.

METHODS AND RESULTS: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002).

CONCLUSIONS: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.}, } @article {pmid16841753, year = {2006}, author = {Garamvölgyi, R and Petrási, Z and Hevesi, A and Jakab, C and Vajda, Z and Bogner, P and Repa, I}, title = {Magnetic resonance imaging technique for the examination of canine mammary tumours.}, journal = {Acta veterinaria Hungarica}, volume = {54}, number = {2}, pages = {143-159}, doi = {10.1556/AVet.54.2006.2.1}, pmid = {16841753}, issn = {0236-6290}, mesh = {Animals ; Carcinoma, Ductal, Breast/blood supply/pathology/*veterinary ; Dog Diseases/*pathology ; Dogs ; Female ; Magnetic Resonance Imaging/methods/*veterinary ; Mammary Neoplasms, Animal/blood supply/*pathology ; Mixed Tumor, Malignant/blood supply/pathology/*veterinary ; Neovascularization, Pathologic/pathology/veterinary ; }, abstract = {The aim of this study was to adapt the human magnetic resonance imaging (MRI) sequences for use in the routine examination of canine mammary glands. MRI was performed on 10, middle- to old-aged dogs of different breeds. It was found that T1- and T2-weighted spin echo, short T1 inversion recovery sequences and a gradient echo (GE) dynamic T1-weighted measurement made in the coronal and transversal planes were the most informative MR diagnostic methods for imaging canine mammary tumours. The static MR technique is the most detailed imaging modality for differentiating the tissue types in the substance of the mammary gland. The MRI findings were in close relationship with the histological result (five malignant mixed tumours and five cases of invasive ductal carcinoma). Using the GE dynamic contrast-enhanced sequence the morphological patterns as well as the kinetic parameters proved to be malignant. By the dynamic measurement technique initial information was obtained on the contrast enhancing properties, which are valuable factors during in vivo staging and in the prognostic work.}, } @article {pmid16839413, year = {2006}, author = {Tsutsui, S and Yasuda, K and Suzuki, K and Takeuchi, H and Nishizaki, T and Higashi, H and Era, S}, title = {Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer.}, journal = {BMC cancer}, volume = {6}, number = {}, pages = {187}, pmid = {16839413}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cyclin-Dependent Kinase Inhibitor p27/*metabolism ; Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Lymphatic Metastasis/pathology ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated.

METHODS: The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously.

RESULTS: The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS.

CONCLUSION: The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.}, } @article {pmid16828238, year = {2006}, author = {Bircan, S and Kapucuoglu, N and Baspinar, S and Inan, G and Candir, O}, title = {CD24 expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.}, journal = {Pathology, research and practice}, volume = {202}, number = {8}, pages = {569-576}, doi = {10.1016/j.prp.2006.05.004}, pmid = {16828238}, issn = {0344-0338}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; CD24 Antigen/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Membrane/metabolism/pathology ; Cytoplasm/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques/*methods ; Middle Aged ; Pilot Projects ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {CD24 is a small, heavily glycosylated cell surface protein, that is expressed in a large variety of solid tumors. It is considered to play an important role in tumor progression and metastasis. We aimed to evaluate CD24 expression in invasive ductal carcinomas (IDCa), ductal carcinoma in situ (DCIS) and non-tumorous breast tissues, and to investigate the relationship between histopathological parameters, estrogen and progesterone receptors, and c-erbB2 expressions. The study included 34 IDCa, 25 DCIS, and 13 non-tumorous breast tissues. All cases were reevaluated histopathologically, and immunohistochemistry was performed with monoclonal CD24 antibody. The results clearly demonstrated that CD24 expression, including membranous and cytoplasmic staining, was significantly higher in DCIS and IDCa than in the non-tumorous breast (p=0.001, p=0.000, and p=0.035, p=0.000, respectively). Cytoplasmic staining was detected predominantly in neoplastic tissues and was significantly increased in high grade DCIS (p=0.013). In invasive carcinomas, although the level of membranous staining was significantly positively correlated with tumor grade (p=0.040), there was no such an association with the cytoplasmic level. However, it showed a trend towards pT (p=0.089). In conclusion, our results suggest that higher CD24 expression may be associated with malignant transformation and progression in breast cancer biology. Furthermore, higher membranous expression and, in particular, cytoplasmic staining seem to predict malignant transformation, and different patterns of CD24 expression may be associated with different pathological features in breast tumors.}, } @article {pmid16826579, year = {2006}, author = {Tham, YL and Sexton, K and Kramer, R and Hilsenbeck, S and Elledge, R}, title = {Primary breast cancer phenotypes associated with propensity for central nervous system metastases.}, journal = {Cancer}, volume = {107}, number = {4}, pages = {696-704}, doi = {10.1002/cncr.22041}, pmid = {16826579}, issn = {0008-543X}, support = {P01 CA 30195/CA/NCI NIH HHS/United States ; P20 CA 1033698/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/metabolism ; Brain Neoplasms/metabolism/mortality/*secondary ; Breast Neoplasms/metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/metabolism/mortality/*secondary ; Carcinoma, Intraductal, Noninfiltrating/metabolism/mortality/*secondary ; Carcinoma, Lobular/metabolism/mortality/*secondary ; ErbB Receptors/metabolism ; Female ; Humans ; Incidence ; Middle Aged ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm Staging ; Phenotype ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {BACKGROUND: There is anecdotal evidence that the incidence of central nervous system (CNS) metastases in breast cancer patients is increasing. It is unclear whether specific tumor biological properties or the use of systemic therapies influence this risk.

METHODS: Using a database of 10,782 patients, 2685 patients were identified who experienced recurrence distantly. Clinical and biological features were analyzed in 2 ways: (1) patients who ever had versus those who never had CNS metastases, and (2) CNS metastases as the first site of recurrence versus those who had other sites. Correlations of survival after CNS metastasis with clinical and biologic features were also analyzed.

RESULTS: In the ever versus never analysis, CNS metastases were significantly associated with younger age, premenopausal status, infiltrating ductal carcinoma histology (IDC), estrogen receptor (ER) and progesterone receptor (PR) negativity, low Bcl-2, high S-phase, aneuploidy, and altered p53. Tumor size, lymph node status, and use of adjuvant systemic therapy played little role. HER-2 overexpression was not associated with an increased risk in these patients (none of whom were treated with trastuzumab) (P = .91). However, epidermal growth factor receptor (EGFR) overexpression was associated with increased risk (P = .02). A multivariate analysis revealed ER negativity (odds ratio [OR] 2.8, P < .001), IDC histology (OR 2.5, P = .02), and young age (P < .001) as independent factors for CNS metastases. The clinical and biologic profiles of primary tumors with CNS metastases at first recurrence did not differ from those with CNS metastases after recurrence to other sites, except for HER-2 status. HER-2-positive tumors were not more likely to undergo recurrence initially in the CNS (P =.04). The median survival after CNS metastases was 5.5 months and HER-2-positive patients had a shorter survival.

CONCLUSIONS: Younger patients with hormone receptor-negative, highly proliferative, genomically unstable, and p53-altered tumors were at increased relative risk for CNS metastases. HER-2 expression and adjuvant systemic therapies did not increase this risk.}, } @article {pmid16807982, year = {2006}, author = {Kim, HJ and Park, CI and Park, BW and Lee, HD and Jung, WH}, title = {Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast.}, journal = {Yonsei medical journal}, volume = {47}, number = {3}, pages = {333-342}, pmid = {16807982}, issn = {0513-5796}, mesh = {Breast Neoplasms/genetics/*physiopathology ; Carcinoma in Situ/genetics/*physiopathology ; Carcinoma, Ductal, Breast/genetics/*physiopathology ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinases/*genetics ; Matrix Metalloproteinases, Membrane-Associated ; RNA, Messenger/metabolism ; Tissue Inhibitor of Metalloproteinase-2/genetics ; }, abstract = {We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.}, } @article {pmid16800895, year = {2006}, author = {Rubinstein, WS and Latimer, JJ and Sumkin, JH and Huerbin, M and Grant, SG and Vogel, VG}, title = {Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for the detection of breast cancer in young, high-risk women.}, journal = {BMC women's health}, volume = {6}, number = {}, pages = {10}, pmid = {16800895}, issn = {1472-6874}, support = {R29 CA071894/CA/NCI NIH HHS/United States ; R29 CA071894-03/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Evidence-based screening guidelines are needed for women under 40 with a family history of breast cancer, a BRCA1 or BRCA2 mutation, or other risk factors. An accurate assessment of breast cancer risk is required to balance the benefits and risks of surveillance, yet published studies have used narrow risk assessment schemata for enrollment. Breast density limits the sensitivity of film-screen mammography but is not thought to pose a limitation to MRI, however the utility of MRI surveillance has not been specifically examined before in women with dense breasts. Also, all MRI surveillance studies yet reported have used high strength magnets that may not be practical for dedicated imaging in many breast centers. Medium strength 0.5 Tesla MRI may provide an alternative economic option for surveillance.

METHODS: We conducted a prospective, nonrandomized pilot study of 30 women age 25-49 years with dense breasts evaluating the addition of 0.5 Tesla MRI to conventional screening. All participants had a high quantitative breast cancer risk, defined as > or = 3.5% over the next 5 years per the Gail or BRCAPRO models, and/or a known BRCA1 or BRCA2 germline mutation.

RESULTS: The average age at enrollment was 41.4 years and the average 5-year risk was 4.8%. Twenty-two subjects had BIRADS category 1 or 2 breast MRIs (negative or probably benign), whereas no category 4 or 5 MRIs (possibly or probably malignant) were observed. Eight subjects had BIRADS 3 results, identifying lesions that were "probably benign", yet prompting further evaluation. One of these subjects was diagnosed with a stage T1aN0M0 invasive ductal carcinoma, and later determined to be a BRCA1 mutation carrier.

CONCLUSION: Using medium-strength MRI we were able to detect 1 early breast tumor that was mammographically undetectable among 30 young high-risk women with dense breasts. These results support the concept that breast MRI can enhance surveillance for young high-risk women with dense breasts, and further suggest that a medium-strength instrument is sufficient for this application. For the first time, we demonstrate the use of quantitative breast cancer risk assessment via a combination of the Gail and BRCAPRO models for enrollment in a screening trial.}, } @article {pmid16800732, year = {2006}, author = {Zhang, Y and Bhat, I and Zeng, M and Jayal, G and Wazer, DE and Band, H and Band, V}, title = {Human kallikrein 10, a predictive marker for breast cancer.}, journal = {Biological chemistry}, volume = {387}, number = {6}, pages = {715-721}, doi = {10.1515/BC.2006.090}, pmid = {16800732}, issn = {1431-6730}, support = {CA 76118/CA/NCI NIH HHS/United States ; CA 87986/CA/NCI NIH HHS/United States ; CA 99163/CA/NCI NIH HHS/United States ; CA 99900/CA/NCI NIH HHS/United States ; CA81076/CA/NCI NIH HHS/United States ; CA94143/CA/NCI NIH HHS/United States ; CA96844/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/diagnosis/genetics/*pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; In Vitro Techniques ; Kallikreins/*analysis/genetics ; Neoplasms ; Prognosis ; RNA, Messenger/analysis ; }, abstract = {Our laboratory is involved in identifying genes that can be used as early diagnostic or prognostic markers in breast cancer. We previously identified a gene (NES1) that is expressed in normal but not in transformed mammary epithelial cells (MECs). NES1 is located on chromosome 19q13.4 within the kallikrein locus and thus was designated as human kallikrein 10 (hK10), although we have been unable to detect any protease activity. Importantly, hK10 expression is decreased in a majority of breast cancer cell lines. Transfection of hK10 into hK10-negative breast cancer cells reduces the tumorigenicity. Using methylation-specific PCR and subsequent sequencing, we demonstrate a strong correlation between hypermethylation of hK10 and loss of mRNA expression. Further analysis showed that essentially 100% of normal breast specimens had hK10 expression, whereas 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) samples lacked the hK10 mRNA. Importantly, hK10-negative DCIS diagnosed at the time of biopsy were subsequently diagnosed as IDC at the time of definitive surgery. It has been shown that hK10 protein expression is regulated by steroids. In addition to breast cancers, hK10 is downregulated in cervical cancer, prostate cancer and acute lymphocytic leukemia, whereas it is upregulated in ovarian cancers. These results point to the paradoxical role of hK10 in human cancers and underscore the importance of further studies of this kallikrein.}, } @article {pmid16796889, year = {2006}, author = {Zhang, N and Tong, YJ and Shan, ZY and Teng, WP}, title = {[Effect of chronic mild and moderate iodine excess on thyroid anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats].}, journal = {Zhonghua yi xue za zhi}, volume = {86}, number = {18}, pages = {1274-1278}, pmid = {16796889}, issn = {0376-2491}, mesh = {Animals ; Chronic Disease ; Deficiency Diseases/drug therapy/metabolism ; Dietary Supplements ; Dose-Response Relationship, Drug ; Female ; Glutathione Peroxidase/metabolism ; Goiter, Endemic/*drug therapy/metabolism ; Hydrogen Peroxide/metabolism ; Iodine/*administration & dosage/*deficiency/urine ; Male ; Malondialdehyde/metabolism ; Oxidative Stress/*drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Superoxide Dismutase/metabolism ; Thyroid Gland/drug effects/metabolism/pathology ; }, abstract = {OBJECTIVE: To investigate the effects of chronic mild and moderate iodine excess on thyroid oxidative injury and anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats.

METHODS: Four-week-old Wistar rats were fed with iodine deficient diet for three months to make iodine deficient goiter models, then divided randomly into three groups: iodine deficient control group (Group IDC) fed with double distilled water, iodine-supplement group I (Group IS I) fed with potassium iodate solutions with the iodine concentrations of 100 microg/L, and iodine-supplement group II (Group IS II), fed with potassium iodate solution with the iodine concentrations of 330 microg/L. Another four-week-old Wistar rats were fed with normal diet for three months, and then divided randomly into three groups: normal control group (NC) fed with double distilled water, iodine-excess group I (IEI) fed with potassium iodate solution with the iodine concentration of 300 microg/L, and iodine-excess group II (Group IEII), fed with potassium iodate solution with the iodine concentration of 660 microg/L. 1, 2, 4, 8, and 24 weeks after treatment samples of urine were collected to detect the median urine iodine (MUI), samples of plasma were collected from the hearts of 8-14 rats from each group and then rats were killed. Their thyroid glands were taken out to measure the wet weight and made into homogenate. Biochemical method was used to measure the activities of glutathione-peroxidase (GSH-P(X)) and superoxide dismutase (SOD) as well as the contents of malonyldialdehyde (MDA) and H2O2 in the homogenates of thyroid glands.

RESULTS: The GSH-P(X) activity 2 weeks after treatment of Group IS II was significantly lower than that of Group IDC (P < 0.05), and the GSH-P(X) activity 4 weeks after treatment of Group IS I was significantly lower than that of Group IDC (P < 0.001). The activities of GSH-P(X) 4, 8, and 24 weeks after treatment of Groups IS I and IS II were all lower than those of Group C at the same time points significantly (P < 0.001, < 0.01, and < 0.05 respectively). The activities of SOD were decreased gradually in Groups IS I and IS II and were significantly lower than those of Group IDC since 8 weeks after treatment (P < 0.001 or < 0.05). The SOD activities in thyroid glands of Groups IEI and IEII since 8 weeks after treatment decreased significantly in comparison with Group NC (all P < 0.01 or < 0.001). The contents of H2O2 in thyroid glands of Groups IS I and IS II were significantly lower than those of Group IDC at different time points (P < 0.001, < 0.01, or < 0.05), and were significantly lower than those of Group NC 8 and 24 weeks after treatment (P < 0.001 or < 0.01). The contents of MDA in thyroid glands since 2 weeks after treatment of Group IEI were all significantly lower than those of Group IDC at the same time points (all P < 0.05), and the content of MDA in thyroid glands since 1 week after treatment of Groups IS II were all significantly lower than those of Group IDC at the same time points (all P < 0.05).

CONCLUSION: Supplementation of 100 microg/L and 330 microg/L iodine on iodine deficiency Wistar rats may alleviate the oxidative injury but weaken the anti-oxidative protection of thyroid. The anti-oxidative protection of thyroid glands of non-iodine deficiency Wistar rats may also be weakened by supplementation of 300 microg/L and 660 microg/L iodine.}, } @article {pmid16791737, year = {2006}, author = {Wei, Y and Werner, MH}, title = {iDC: A comprehensive toolkit for the analysis of residual dipolar couplings for macromolecular structure determination.}, journal = {Journal of biomolecular NMR}, volume = {35}, number = {1}, pages = {17-25}, pmid = {16791737}, issn = {0925-2738}, mesh = {*Algorithms ; Nuclear Magnetic Resonance, Biomolecular/*methods ; Nucleic Acid Conformation ; Nucleic Acids/chemistry ; Protein Conformation ; Proteins/chemistry ; *Software ; User-Computer Interface ; }, abstract = {Measurement of residual dipolar couplings (RDCs) has become an important method for the determination and validation of protein or nucleic acid structures by NMRf spectroscopy. A number of toolkits have been devised for the handling of RDC data which run in the Linux/Unix operating environment and require specifically formatted input files. The outputs from these programs, while informative, require format modification prior to the incorporation of this data into commonly used personal computer programs for manuscript preparation. To bridge the gap between analysis and publication, an easy-to-use, comprehensive toolkit for RDC analysis has been created, iDC. iDC is written for the WaveMetrics Igor Pro mathematics program, a widely used graphing and data analysis software program that runs on both Windows PC and Mac OS X computers. Experimental RDC values can be loaded into iDC using simple data formats accessible to Igor's tabular data function. The program can perform most useful RDC analyses, including alignment tensor estimation from a histogram of RDC occurrence versus values and order tensor analysis by singular value decomposition (SVD). SVD analysis can be performed on an entire structure family at once, a feature missing in other applications of this kind. iDC can also import from and export to several different commonly used programs for the analysis of RDC data (DC, PALES, REDCAT) and can prepare formatted files for RDC-based refinement of macromolecular structures using XPLOR-NIH, CNS and ARIA. The graphical user interface provides an easy-to-use I/O for data, structures and formatted outputs.}, } @article {pmid16789413, year = {2006}, author = {Kigure, S}, title = {Immunohistochemical study of the association between the progression of pancreatic ductal lesions and the expression of MUC1, MUC2, MUC5AC, and E-cadherin.}, journal = {Rinsho byori. The Japanese journal of clinical pathology}, volume = {54}, number = {5}, pages = {447-452}, pmid = {16789413}, issn = {0047-1860}, mesh = {Antigens, Neoplasm/*analysis ; Cadherins/*analysis ; Carcinoma, Pancreatic Ductal/*pathology ; Disease Progression ; Humans ; Immunohistochemistry ; Mucin 5AC ; Mucin-1 ; Mucin-2 ; Mucins/*analysis ; Pancreatic Ducts/chemistry/pathology ; Pancreatic Neoplasms/*pathology ; Pancreatitis/metabolism/pathology ; }, abstract = {Pancreatic cancer is a highly malignant tumor. In this study, we examined the association between the expression of MUC1, MUC2, MUC5AC, and E-cadherin, and the pathological changes from normal pancreatic tissue to invasive ductal carcinoma(IDC). Since MUC1 is known to be involved in the inhibition of E-cadherin, we also examined the association between MUC1 and E-cadherin. Five normal pancreatic tissues, 6 chronic pancreatitis tissues, 20 pancreatic intraepithelial neoplasia (PanIN) tissues, and 24 IDC tissues were fixed in formalin, embedded in paraffin, and sections were immunostained. MUC1 was positive in nonneoplastic tissues, PanIN-3, and IDC. MUC2 was negative in almost all tissues. MUC5AC was positive in neoplastic tissues. E-cadherin was positive in almost all tissues. Changes in MUC1 staining were observed in PanIN-3 and IDC, and E-cadherin staining was seen in neoplastic tissues. MUC1 was more diffusely positive in lymph node metastasis-positive cases. The expression of MUC1 and MUC5AC is associated with the progression of PanIN. MUC1 may promote the inhibition of E-cadherin. The results also suggest that MUC1 is useful as a prognostic marker.}, } @article {pmid16786567, year = {2006}, author = {Kumar, M and Jagannathan, NR and Seenu, V and Dwivedi, SN and Julka, PK and Rath, GK}, title = {Monitoring the therapeutic response of locally advanced breast cancer patients: sequential in vivo proton MR spectroscopy study.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {24}, number = {2}, pages = {325-332}, doi = {10.1002/jmri.20646}, pmid = {16786567}, issn = {1053-1807}, mesh = {Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*pathology ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Disease Progression ; Doxorubicin/administration & dosage ; Female ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Monitoring, Physiologic/*methods ; Neoadjuvant Therapy ; Protons ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate the use of the water-to-fat (W-F) value obtained from in vivo proton ((1)H) MR spectroscopy (MRS) as a response indicator of cytologically confirmed patients with locally advanced breast cancer (LABC), and to monitor the therapeutic response of such patients to neoadjuvant chemotherapy (NACT).

MATERIALS AND METHODS: Serial (1)H MR spectra were recorded both before and after the completion of chemotherapy in 33 LABC patients (with infiltrating ductal carcinoma (IDC)) at 1.5T. In addition, spectra from normal breast tissues of 28 healthy volunteers were recorded.

RESULTS: Malignant breast tissues showed elevated W-F values compared to normal breast tissues of controls. Statistically significant higher pretherapy W-F value (P < 0.01) was observed in patients compared to controls. In patients who received NACT resulting in the reduction of the primary tumor size, the W-F value showed a decrease that was statistically significant (P < 0.01). Analysis of the MR data further indicates that the W-F value had no correlation with the menstrual status of the patients. A comparison of pretherapy W-F value with pretherapy tumor volume showed a fair correlation (P = 0.05), while the posttherapy W-F value showed no such correlation with the posttherapy tumor volume.

CONCLUSION: This study demonstrates that simple, conventional in vivo (1)H MRS is a useful technique for monitoring the therapeutic response of breast cancer patients. The observed trend in the reduction of W-F value provides a noninvasive response indicator to monitor the clinical outcome of locally advanced breast cancer patients to NACT.}, } @article {pmid16786469, year = {2006}, author = {Wieczorek, M and Hoeltgen, R and Djajadisastra, I}, title = {[Avoidance of intermittent T-wave oversensing with device programming].}, journal = {Herzschrittmachertherapie & Elektrophysiologie}, volume = {17}, number = {2}, pages = {106-111}, pmid = {16786469}, issn = {0938-7412}, mesh = {Adult ; Defibrillators, Implantable/*adverse effects ; Electrocardiography/*methods ; Humans ; Male ; Tachycardia, Ventricular/*etiology/*prevention & control ; Therapy, Computer-Assisted/*methods ; }, abstract = {We report the case of a 35-year-old man who was suffering from severe heart failure due to cardiomyopathy. He underwent heart transplantation years ago and developed complex ventricular arrhythmias in the following months in combination with recurrent episodes of syncope due to hypertrophic non-obstructive cardiomyopathy in the transplanted heart, so a dual chamber ICD was implanted. Months later repetitive episodes of intermittent T-wave oversensing with consecutive activation of the ICD could be observed. Surgical revision of the electrode was performed and the patient was closely followed up. One year later, further episodes of T-wave oversensing led to multiple inappropriate IDC-shocks. A very short AV-conduction time was programmed to allow ventricular capture whenever possible, because T-wave oversense after ventricular capture would be annotated as single ventricular ectopy not resulting in antitachycardia pacing. As a consequence, the patient was free from inappropriate ICD-shocks, but showed several shorter episodes of T-wave oversensing. They were all initiated by atrial activity that was seen in the refractory period, thus leading to a loss of AV synchrony. Programming a very short post ventricular atrial refractory period (PVARP) in addition to a short AV-delay led to the complete disappearance of T-wave oversensing in this patient. During a 9-month follow-up, no further tachycardia episodes were detected by the device.}, } @article {pmid16786147, year = {2006}, author = {Kalfoglou, EA and Faikoglu, R and Ozcan, S and Petridis, G and Yükseloglu, H and Atasoy, S}, title = {DNA analysis as a tool for breast cancer malpractice determination: an interdisciplinary approach.}, journal = {Oncology reports}, volume = {16}, number = {1}, pages = {203-206}, pmid = {16786147}, issn = {1021-335X}, mesh = {Biopsy ; Breast Neoplasms/*genetics/surgery ; DNA/metabolism ; Female ; Humans ; *Malpractice ; Medical Oncology/*legislation & jurisprudence ; Middle Aged ; Polymorphism, Genetic ; *Sequence Analysis, DNA ; Tandem Repeat Sequences/genetics ; }, abstract = {Malpractice in breast cancer can be seen as false-negative or false-positive findings which may result in either late or incorrect therapies. Biopsy material can be unintentionally interchanged, leading to incorrect treatment, and psychological damage to the patient. There is an obvious need for individualization of the tissue samples in such cases. In this study we used a multidisciplinary approach to integrate DNA technology that has been standardized and used in forensic science for other purposes, mainly to prove malpractice that has been the result of interchanging tissue samples in breast cancer. The main focus of the study was to evaluate the applicability of the technique, therefore we studied the samples of a 58-year-old female for whom the result of pathological analysis was reported as 'invasive ductal carcinoma'. The patient was surgically treated by a modified mastectomy technique and referred for chemotherapy. Prior to chemotherapy we found that the tissue samples analyzed did not belong to the patient in question. We used a battery of 15 polymorphic STR loci to identify the sample and we had strong evidence for exclusion of the patient. The analysis was done on both blood and buccal swab of the patient and on the tissue sample. We concluded that the technique is applicable and useful; however care should be taken in the interpretation of the results because the mutations in the tumoral tissues are very well known. Therefore, the maximum of informative loci should be studied and loss of heterozygosity should always be considered. We should also have in mind the possibility of intentional interchange which gives the results value in medico-legal investigations.}, } @article {pmid16785780, year = {2006}, author = {Vogl, G and Bartel, H and Dietze, O and Hauser-Kronberger, C}, title = {HER2 is unlikely to be involved in directly regulating angiogenesis in human breast cancer.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {14}, number = {2}, pages = {138-145}, doi = {10.1097/01.pai.0000168591.58721.a6}, pmid = {16785780}, issn = {1541-2016}, mesh = {Angiogenesis Inducing Agents/analysis/*metabolism ; Breast Neoplasms/*etiology ; Carcinoma, Ductal, Breast/*etiology ; Female ; Humans ; Immunohistochemistry/methods ; Neovascularization, Pathologic/*etiology ; Prognosis ; Receptor, ErbB-2/*physiology ; Receptors, Growth Factor/analysis/classification/*metabolism ; Up-Regulation ; }, abstract = {Angiogenesis is a fundamental component of oncogenesis. Angiogenic factors such as vascular endothelial growth factor (VEGF) and platelet derived-endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) are generated from tumor cells to provide tumor growth and are thought to be regulated via the HER2 oncogene, whose amplification is the most common genetic alteration in breast cancer. The present study aimed to evaluate the immunoreactivity of angiogenic factors (VEGF, PD-ECGF/TP) and microvessel density (MVD) via epidermal growth factor receptor (EGFR) and HER2, and to correlate their expression with clinicopathologic features. Two hundred one invasive human breast cancer specimens were tested immunohistochemically for the expression of these proteins. In addition, MVD was examined using computerized image analysis. VEGF could be an additional interesting prognostic variable, as it was significantly associated with tumor grade (P=0.002), stage (P=0.018), and negative estrogen receptor status (P=0.011). EGFR was significantly related to invasive ductal carcinoma (P=0.030), tumor grade (P=0.009), VEGF expression (P=0.013), PD-ECGF/TP expression (P=0.024), and MVD (P=0.050). The finding that VEGF is not correlated to MVD does not rule out a crucial role of VEGF as a key factor in angiogenesis. HER2 could not be correlated to MVD, VEGF expression, or PD-ECGF/TP expression, indicating that this factor is unlikely to be involved in directly regulating angiogenesis, whereas the significant correlations between EGFR and histologic tumor type, tumor grade, the angiogenic factors VEGF and PD-ECGF/TP, and MVD point out that EGF is the major modulating growth factor for angiogenesis in breast cancer.}, } @article {pmid16782429, year = {2006}, author = {Eguchi, H and Ishikawa, O and Ohigashi, H and Tomimaru, Y and Sasaki, Y and Yamada, T and Tsukuma, H and Nakaizumi, A and Imaoka, S}, title = {Patients with pancreatic intraductal papillary mucinous neoplasms are at high risk of colorectal cancer development.}, journal = {Surgery}, volume = {139}, number = {6}, pages = {749-754}, doi = {10.1016/j.surg.2005.11.008}, pmid = {16782429}, issn = {0039-6060}, mesh = {Adenocarcinoma, Mucinous/*complications ; Aged ; Carcinoma, Pancreatic Ductal/*complications ; Carcinoma, Papillary/*complications ; Colorectal Neoplasms/*etiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Pancreatic Neoplasms/*complications ; Risk ; }, abstract = {BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been recognized recently and is being diagnosed with increasing frequency. Although IPMN has a more favorable prognosis than standard invasive ductal carcinoma (IDC) of the pancreas, recent reports suggest that IPMN patients are at higher risks of synchronous or metachronous primary cancers arising from various organs other than the pancreas (extrapancreatic cancers).

METHODS: Records of 370 patients (69 of IPMN, 301 of IDC) who underwent surgery were used to assess risk factors for preoperative or postoperative extrapancreatic cancers. To calculate the rate of increase of extrapancreatic cancers in IPMN patients, compared with the normal population, the observed/expected ratio (O/E ratio) was calculated by using the Osaka Cancer Registry, one of the world largest cancer databases.

RESULTS: The incidence of preoperative extrapancreatic cancers was significantly higher in IPMN patients (28%, 19 patients) than that in IDC (9%, 27 patients). In the IPMN-group, the preoperative incidence of colorectal cancer was 12% followed by gastric cancer at 4%. Logistic regression analysis showed IPMN and age to be independent risk factors for preoperative colorectal cancer development. The O/E ratio of preoperative colorectal cancer was significantly high in IPMN patients (5.37; 95% confidence interval, 2.31-10.58) but not in IDC patients (1.24; 95% confidence interval, 0.46-2.70). The incidence of postoperative extrapancreatic cancers also was significantly higher in IPMN patients (15%, 10 patients) than that in IDC (4%, 12 patients). During the postoperative follow-up, 4% of IPMN (3 patients) and 0.7% of IDC (2 patients) died from extrapancreatic cancers.

CONCLUSIONS: Our results indicate that IPMN patients are at significantly higher risks of extrapancreatic cancers including colorectal cancer. A careful systemic checkup is therefore required for preoperative screening and postoperative follow-up for IPMN patients.}, } @article {pmid16780019, year = {2006}, author = {Sauer, T and Garred, O and Lømo, J and Naess, O}, title = {Assessing invasion criteria in fine needle aspirates from breast carcinoma diagnosed as DICS or invasive carcinoma: can we identify an invasive component in addition to DCIS?.}, journal = {Acta cytologica}, volume = {50}, number = {3}, pages = {263-270}, doi = {10.1159/000325952}, pmid = {16780019}, issn = {0001-5547}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; Neoplasm Invasiveness/*pathology ; }, abstract = {OBJECTIVE: To evaluate invasion criteria in fine needle aspiration cytology (FNAC) of histologically diagnosed breast ductal carcinoma in situ (DCIS) and invasive carcinoma and to evaluate their usefulness in identifying an invasive component in addition to DCIS.

STUDY DESIGN: The material consisted of 331 smears diagnosed as suspicious for or consistent with DCIS and in which histology had shown either DCIS or invasive ductal carcinoma. All smears were reevaluated for the following invasion criteria: invasion of fat or fibrous tissue fragments, fibroblast proliferation, cell-poor elastoid tissue fragments, tubular structures and intracytoplasmic vacuoles.

RESULTS: All invasion criteria except cytoplasmic vacuoles correlated with invasiveness, but none of them were found exclusively in invasive lesions. Pseudoinvasion in fibrous or fatty tissue fragments were found in 8 cases of histologic pure DCIS. One DCIS (0.4%) revealed > or = 2 invasion features as well as 22 invasive carcinomas (20.7%), representing 7.4% of all cases.

CONCLUSION: Using established invasion criteria, practically no pure DCIS lesion will be diagnosed as invasive on FNAC, but one will identify only a subset of cases harboring an invasive component.}, } @article {pmid16778390, year = {2006}, author = {Jo, BH and Chun, YK}, title = {Heterogeneity of invasive ductal carcinoma: proposal for a hypothetical classification.}, journal = {Journal of Korean medical science}, volume = {21}, number = {3}, pages = {460-468}, pmid = {16778390}, issn = {1011-8934}, mesh = {Adult ; Aged ; Breast Neoplasms/*classification/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*classification/*diagnosis/pathology ; Cell Nucleus/metabolism ; *Classification ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Time Factors ; Treatment Outcome ; }, abstract = {To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.}, } @article {pmid16769196, year = {2006}, author = {Wu, YC and Chen, DR and Kuo, SJ}, title = {Personal experience of ultrasound-guided 14-gauge core biopsy of breast tumor.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {32}, number = {7}, pages = {715-718}, doi = {10.1016/j.ejso.2006.04.012}, pmid = {16769196}, issn = {0748-7983}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Biopsy, Fine-Needle ; Breast/pathology ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; False Negative Reactions ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; *Ultrasonography, Interventional ; }, abstract = {AIM: This study was aimed to examine the efficacy of ultrasound-guided core needle biopsy of breast tumor and compared with the results of previous publications.

METHODS: From January 2001 to September 2003, 546 lesions in 513 consecutive patients with the identification of a tumor on ultrasound examination categorized belong and above C3 according to BIRADS (Breast Image Reporting and Data Systems). A minimum of three samples was taken during the biopsy process.

RESULTS: The patients' ages ranged from 17 to 89 years (mean, 43 years); tumors were from 5.7 to 41.6 mm in diameter (mean, 20.3 mm). There were 341 lesions with benign findings, 202 lesions with malignancy and 3 lesions with atypical ductal hyperplasia (ADH). Underestimates were found in five patients. Two patients were "ADH-DCIS (ductal carcinoma in situ) underestimate", and three patients were "DCIS-IDC (invasive ductal carcinoma) underestimate". The ADH underestimation rate was 40% (2/5) and DCIS underestimation rate was 43% (3/7). No false-positive results were observed. According to this study, the accuracy rate was 99%, sensitivity rate 97.6%, specificity rate 100%, and false-negative rate 2.4%.

CONCLUSIONS: Both palpable and impalpable breast lesions should be examined under image guidance and automated core biopsy is the technique of first choice. Fourteen-gauge core biopsy can provide a definitive diagnosis in 99% of solid tumors in this series.}, } @article {pmid16762512, year = {2006}, author = {Gong, N and Zhao, Y and Dong, C and Chen, ZK}, title = {Negative costimulatory molecules: the proximal of regulatory T cells?.}, journal = {Medical hypotheses}, volume = {67}, number = {4}, pages = {841-847}, doi = {10.1016/j.mehy.2006.04.013}, pmid = {16762512}, issn = {0306-9877}, mesh = {Abatacept ; Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; CD28 Antigens/immunology ; CD4 Antigens/immunology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Immunoconjugates/immunology ; L-Selectin/immunology ; Leukocyte Common Antigens/immunology ; Ligands ; Lymphocyte Activation ; Models, Immunological ; Receptors, Interleukin-2/immunology ; Signal Transduction ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells (Tregs) are a central mechanism of immune regulation. It is well known that their regulatory effect is antigen-specific and depends on cell-cell contact. In addition, some immunological phenomenon such as linked suppression and iDC-induced tolerance are related with Tregs. But the surface markers, which reliably distinguish Treg from other T cell populations, and the regulatory mechanism still remain to be further revealed. Negative costimulatory molecule (NCM) family is one natural intrinsic mechanism that delivers the negative signal into cytoplasma to modulate immunoresponse and its expression can be induced not only on the immune cells but also on the parenchymal cells. Based on the present knowledge, we hypothesize NCMs are the specific surface markers to define Tregs. Tregs are one kind of activated T cells with high expression of NCM receptor and have the capability to induce NCM ligands expression on the membrane of APCs and the target cells of the activated cells. The NCM receptor-ligand complexes deliver negative signal into lymphocytes to regulate the immune response. This hypothesis remains to be fully elucidated.}, } @article {pmid16762272, year = {2006}, author = {Ruibal, A and Garrido Pumar, M and Arias, JI}, title = {[Preoperative serum CA15.3 and CEA levels and clinical-biological parameters in breast tumors].}, journal = {Revista espanola de medicina nuclear}, volume = {25}, number = {3}, pages = {180-183}, doi = {10.1157/13088414}, pmid = {16762272}, issn = {0212-6982}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biomarkers, Tumor/analysis/*blood ; Breast Neoplasms/*blood/chemistry/pathology/surgery ; Carcinoembryonic Antigen/*analysis ; Carcinoma, Ductal, Breast/*blood/chemistry/secondary/surgery ; Cathepsin D/analysis ; Cytosol/chemistry ; ErbB Receptors/analysis ; Female ; Humans ; Hyaluronic Acid/analysis ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Mucin-1/*blood ; Neoplasm Proteins/analysis/blood ; Receptors, Estrogen/analysis ; Sensitivity and Specificity ; Trefoil Factor-1 ; Tumor Burden ; Tumor Suppressor Proteins/analysis ; }, abstract = {OBJECTIVE: To study the possible associations between preoperative serum CEA and CA15.3 levels and different clinical-biological parameters of infiltrating ductal carcinomas of the breast (IDC).

PATIENTS AND METHOD: Preoperative serum CA15.3 and CEA levels were determined in 255 and 224 females, respectively, having IDC. We assayed the cytosolic levels of estrogen receptor, pS2, cathepsin D and hyaluronic acid, as well as the levels of epidermal growth factor receptor in cell surfaces. Tumor size, axillary involvement (N), distant metastasis (M), histological grade (HG) and cellular S-phase (SP) were taken into account.

RESULTS: 22 IDC were positive for CA15.3 (> 40 U/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p: 0.005) and distant metastasis (p < 0.001). 19 IDC were positive for CEA (> 4 ng/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p < 0.001), > 5 cm (p: 0.052) and global S-phase values (p: 0.062), and were more frequently N + (p: 0.045), > 3N + (p: 0.001) and > 10N + (p < 0.001), M + (p: 0.004), HG3 (p: 0.091) and SP > 7 % (p: 0.006).

CONCLUSIONS: Our results led us to the following: In patients having IDC of the breast, preoperative serum CA15.3 levels are associated with greater tumor size and distant metastasis, while pre-treatment CEA serum levels are associated moreover with axillary involvement; we have not observed any correlation between serum levels of both antigens and the hormonal status of the tumor; these results had physiopathological interest but reduced clinical value in pretreatment breast carcinomas due to their low sensitivity of both markers. However, they are useful in the follow-up of the patients when assessing serum concentrations of both markers, since they contribute to knowing the patients' clinical status better.}, } @article {pmid16755121, year = {2006}, author = {Kijima, Y and Umekita, Y and Yoshinaka, H and Owaki, T and Sakamoto, A and Yoshida, H and Aikou, T}, title = {A case of breast carcinoma with cartilaginous and osseous metaplasia.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {2}, pages = {214-219}, doi = {10.2325/jbcs.13.214}, pmid = {16755121}, issn = {1340-6868}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Biopsy, Needle ; Bone Neoplasms/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/*secondary/surgery ; Carcinosarcoma/pathology/*secondary/surgery ; Diagnosis, Differential ; Disease Progression ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/pathology/*secondary ; Magnetic Resonance Imaging ; Mammography ; Mastectomy, Segmental ; Metaplasia ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/*pathology ; Risk Assessment ; }, abstract = {We report a case of a 49-year-old Japanese woman diagnosed with breast carcinoma with osseous and cartilaginous metaplasia with a poor outcome. Histological examination revealed invasive ductal carcinoma with undifferentiated sarcomatous components including chondrosarcomatous areas. Osseous metaplasia was also noted in a very limited area. Neither axillary lymph node metastases nor vessel invasion were observed. Immunohistochemical examination was negative for estrogen receptor, progesterone receptor and HER2 overexpression. Stage II A T2N0M0 carcinoma was diagnosed postoperatively. Five months after the operation, she developed lung metastases. Although she received systemic chemotherapy, the lesions increased in number and grew rapidly. She died of pulmonary distress 5 months after relapse.}, } @article {pmid16755106, year = {2006}, author = {Sasano, H and Suzuki, T and Nakata, T and Moriya, T}, title = {New development in intracrinology of breast carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {13}, number = {2}, pages = {129-136}, doi = {10.2325/jbcs.13.129}, pmid = {16755106}, issn = {1340-6868}, mesh = {17-Hydroxysteroid Dehydrogenases/*metabolism ; Adult ; Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy, Needle ; Breast Neoplasms/drug therapy/*enzymology/pathology ; Disease Progression ; Estrogens/analysis/*metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Hormone-Dependent/drug therapy/*enzymology ; Sensitivity and Specificity ; Steryl-Sulfatase/*metabolism ; Sulfotransferases/*metabolism ; }, abstract = {Intratumoral metabolism and synthesis of estrogens as a result of the interactions of various enzymes are considered to play very important roles in the pathogenesis and development of hormone dependent breast carcinoma. Among these enzymes, intratumoral aromatase plays as important role converting serum androgens to estrogens in situ, and serves as a source of estrogen, especially in postmenopausal patients with breast carcinoma. However, other enzymes such as the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, estrogen sulfatase (STS) and estrogen sulfotransferase, also play pivotal roles in intratumoral estrogen production. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone (E1), and thereby serve to modulate the tissue levels of bioactive E2 in human breast carcinoma. 17Beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17beta-HSD type 2 catalyzes primarily the oxidation of E2 to E1. In human breast disease, 17beta-HSD type 1 is expressed in proliferative disease without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17Beta-HSD type 2 has not been detected in any of these breast lesions. In addition, 17beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E1, produced as a result of in situ aromatization, to E2, a biologically potent estrogen, which exerts estrogenic actions on tumor cells through estrogen receptor, especially the alpha subtype in carcinoma cells. Therefore, inhibiting intratumoral 17beta-HSD type 1 is also considered to contribute to inhibition of cell proliferation by decreasing intratumoral estradiol. Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, while steroid sulfatase (STS) hydrolyzes estrone sulfate (E1-S) to estrone. EST immunoreactivity was recently demonstrated to be significantly associated with a decreased risk of recurrence or improved prognosis by both uni- and multivariate analyses. STS immunoreactivity was significantly associated with an increased risk of recurrence by univariate analysis. These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma. Therefore, the inhibition of intratumoral STS might also serve as an endocrine therapy in postmenopausal patients. It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer. These findings indicate that there are patients who could benefit more from inhibition of these intratumoral enzymes rather than aromatase inhibition as an endocrine therapy. Therefore, it will become very important to examine the intratumoral levels of 17beta-HSD type 1 and STS in the resected specimens of human breast carcinoma as potential targets of novel endocrine therapy in the near future.}, } @article {pmid16753605, year = {2006}, author = {Oakley, GJ and Tubbs, RR and Crowe, J and Sebek, B and Budd, GT and Patrick, RJ and Procop, GW}, title = {HER-2 amplification in tubular carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {126}, number = {1}, pages = {55-58}, doi = {10.1309/E0YE-KHBP-3YYQ-YUBD}, pmid = {16753605}, issn = {0002-9173}, mesh = {Adenocarcinoma/*genetics/metabolism/secondary ; Axilla ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Female ; *Gene Amplification ; Gene Dosage ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Receptor, ErbB-2/*genetics/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; }, abstract = {The prognostic and therapeutic implications of HER-2 gene amplification and estrogen and progesterone receptor status in breast cancer are well described. To address the relative paucity of information concerning HER-2 amplification for tubular carcinomas, we assessed the frequency of gene amplification in 55 tubular carcinomas of the breast from 54 patients, 5 of which had axillary node metastases. The HER-2 gene copy number was assessed by fluorescence in situ hybridization for the majority of tumors analyzed, whereas estrogen and progesterone receptor status was achieved by immunohistochemical analysis. HER-2 gene amplification was not observed in any of the tumors examined, and most were estrogen receptor-positive. This HER-2 gene amplification frequency was significantly lower than the frequency of gene amplification previously reported for all invasive ductal carcinoma of no special type (P < .01). HER-2 gene amplification likely occurs infrequently, or not at all, in tubular carcinomas of the breast, whereas most express estrogen receptors.}, } @article {pmid16752227, year = {2006}, author = {Kawaguchi, T and Takazawa, H and Imai, S and Morimoto, J and Watanabe, T and Kanno, M and Igarashi, S}, title = {Expression of Vicia villosa agglutinin (VVA)-binding glycoprotein in primary breast cancer cells in relation to lymphatic metastasis: is atypical MUC1 bearing Tn antigen a receptor of VVA?.}, journal = {Breast cancer research and treatment}, volume = {98}, number = {1}, pages = {31-43}, doi = {10.1007/s10549-005-9115-6}, pmid = {16752227}, issn = {0167-6806}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/chemistry ; Antigens, Tumor-Associated, Carbohydrate/*biosynthesis ; Breast Neoplasms/*metabolism ; Carbohydrates/chemistry ; Cell Proliferation ; Epitopes/chemistry ; Female ; Glycoproteins/*metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/*biosynthesis ; Plant Lectins/*chemistry/metabolism ; }, abstract = {Aberrant carbohydrate expression frequently occurs in breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of Vicia villosa agglutinin (lectin) (VVA)-binding carbohydrates and aggressive breast cancer. We then investigated the molecular characteristics of these glycoproteins and compared them with those of glycoproteins recognized by the mouse anti-Tn monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive ductal carcinoma demonstrated that VVA-binding carbohydrate expression correlated with tumor stage, lymphatic invasion, and lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major cancer cell-specific VVA-binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the approximately 33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the approximately 30 and approximately 33 kDa molecules was completely lost by preincubation of VVA with 1 mM Tn antigen (N-acetylgalactosamine alpha1-O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in breast cancer cells showed significant correlation with expression of VVA-binding carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to breast cancer aggressiveness. Because anti-Tn MAbs bound to Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of Tn antigen is implicated in aggressive growth of primary breast cancer cells, particularly in lymphatic metastasis.}, } @article {pmid16751301, year = {2007}, author = {Lawson, JS and Tran, DD}, title = {Localised breast cancers may have systemic influences on skin and hair.}, journal = {Journal of clinical pathology}, volume = {60}, number = {2}, pages = {180-184}, pmid = {16751301}, issn = {0021-9746}, mesh = {Biomarkers, Tumor/*metabolism ; Breast/metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Intraductal, Noninfiltrating/metabolism ; Cyclin D1/metabolism ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Neoplasm Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Skin/*metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {HYPOTHESIS: Biomarkers, commonly expressed in breast cancer cells, may be correlated with their expression in breast skin of the same subjects.

METHODS: The expression of biomarkers in specimens from 33 breast tumours and breast skin from the same subject and from 32 normal controls was studied using immunohistochemical techniques.

RESULTS: (1) In normal women, there are significant correlations between the levels of expression of cyclin D1, bcl-2 and p53 in normal breast epithelial cells and breast skin epithelial cells. (2) These patterns of biomarker expression in normal women are similar in breast cancer and breast skin epithelial cells of women with invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS), but are at significantly higher levels in both breast cancer cells and skin from the same subjects. (3) In normal women, human epidermal growth factor receptor 2 (HER-2) is not expressed in either breast epithelial cells or skin epithelial cells. (4) HER-2 is expressed in the breast skin of some subjects with HER-2-positive breast cancer. (5) Positive oestrogen receptor alpha expression occurs significantly more frequently in the breast skin of women with IDC and DCIS than in normal controls.

CONCLUSION: The influence of localised breast cancer seems to be systemic, and leads to changes in skin and hair.}, } @article {pmid16740599, year = {2006}, author = {Tubiana-Hulin, M and Stevens, D and Lasry, S and Guinebretière, JM and Bouita, L and Cohen-Solal, C and Cherel, P and Rouëssé, J}, title = {Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {17}, number = {8}, pages = {1228-1233}, doi = {10.1093/annonc/mdl114}, pmid = {16740599}, issn = {0923-7534}, mesh = {Breast Neoplasms/*drug therapy/mortality/pathology ; Carcinoma, Ductal/*drug therapy/mortality/pathology ; Carcinoma, Lobular/*drug therapy/mortality/pathology ; Female ; Humans ; *Neoadjuvant Therapy ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC).

PATIENTS AND METHODS: We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment.

RESULTS: Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P<0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis.

CONCLUSIONS: ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.}, } @article {pmid16731957, year = {2006}, author = {Holl, V and Peressin, M and Decoville, T and Schmidt, S and Zolla-Pazner, S and Aubertin, AM and Moog, C}, title = {Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells.}, journal = {Journal of virology}, volume = {80}, number = {12}, pages = {6177-6181}, pmid = {16731957}, issn = {0022-538X}, support = {R01 AI036085/AI/NIAID NIH HHS/United States ; AI36085/AI/NIAID NIH HHS/United States ; R01 HL059725/HL/NHLBI NIH HHS/United States ; HL59725/HL/NHLBI NIH HHS/United States ; AI27742/AI/NIAID NIH HHS/United States ; P30 AI027742/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Line ; Dendritic Cells/*virology ; HIV Antibodies/*pharmacology ; HIV-1/*immunology ; Humans ; Immunoglobulin Fab Fragments/pharmacology ; Macrophages/*virology ; Neutralization Tests ; Receptors, IgG ; Virus Replication/drug effects/*immunology ; }, abstract = {Only five monoclonal antibodies (MAbs) neutralizing a broad range of primary isolates (PI) have been identified up to now. We have found that some MAbs with no neutralizing activities according to the "conventional" neutralization assay, involving phytohemagglutinin-stimulated peripheral blood mononuclear cells as targets, efficiently inhibit the replication of human immunodeficiency virus type 1 (HIV-1) PI in macrophages and immature dendritic cells (iDC). The mechanism of inhibition is distinct from the neutralization of infectivity occurring via Fab fragments and involves the interaction of the F portion with the FcgammaRs present on macrophages and iDC. We propose that, if such nonneutralizing inhibitory antibodies limit mucosal HIV transmission, they should be induced by vaccination.}, } @article {pmid16725011, year = {2006}, author = {Shim, HS and Jung, WH and Kim, H and Park, K and Cho, NH}, title = {Expression of androgen receptors and inhibin/activin alpha and betaA subunits in breast apocrine lesions.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {114}, number = {5}, pages = {352-358}, doi = {10.1111/j.1600-0463.2006.apm_321.x}, pmid = {16725011}, issn = {0903-4641}, mesh = {Apocrine Glands/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Female ; Fibrocystic Breast Disease/*metabolism/pathology ; Humans ; Immunohistochemistry ; Inhibin-beta Subunits/*metabolism ; Inhibins/*metabolism ; Metaplasia/*metabolism/pathology ; Papilloma, Intraductal/*metabolism/pathology ; Receptors, Androgen/*metabolism ; Sweat Gland Neoplasms/*metabolism/pathology ; }, abstract = {The importance of androgens and their receptors inhibin and activin remains unknown for mammary epithelial cells. We investigated the role of these hormones in breast apocrine lesions (BAL) using immunohistochemistry to study androgen receptors (AR) and the inhibin/activin alpha and betaA subunits. Forty-two cases of BAL were evaluated, including 22 cases of fibrocystic disease (FCD) showing prominent apocrine changes, 10 intraductal papillomas with extensive apocrine metaplasia, 5 cases of apocrine carcinoma in situ (CIS), and 5 cases of apocrine carcinoma. Fifty non-apocrine lesions were included as controls: 20 cases of FCD, 5 cases of DCIS, and 25 cases of invasive ductal carcinoma. AR was more frequently expressed in BAL than in non-apocrine lesions (p=0.001). AR expression was not related to tumor progression. AR showed a significant positive correlation with betaA subunits (r=0.832, p<0.001), and an inverse correlation with alpha subunits (r=-0.233). The alpha and betaA subunits demonstrated a significant inverse correlation with each other (r=-0.271, p=0.0048). As the expression of the alpha and betaA subunits reflects inhibin and activin A, respectively, AR and activin A may be implicated in apocrine morphogenesis, but not in tumor progression.}, } @article {pmid16721362, year = {2006}, author = {Tsutsui, S and Yasuda, K and Suzuki, K and Takeuchi, H and Nishizaki, T and Higashi, H and Era, S}, title = {A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer.}, journal = {British journal of cancer}, volume = {94}, number = {12}, pages = {1874-1878}, pmid = {16721362}, issn = {0007-0920}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/mortality/*pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis/pathology ; Neoplasm Staging ; Prognosis ; Proto-Oncogene Proteins c-kit/*metabolism ; Survival Analysis ; Survival Rate ; }, abstract = {To evaluate the c-kit expression in breast cancer, 217 invasive ductal carcinomas of the breast were immunohistochemically stained for c-kit protein. The c-kit expression was positive in 59 (27%) of 217 tumours, while the c-kit expression was negative in 158 (73%) of 217 tumours. There was a significant correlation between a negative expression of the c-kit protein and lymph node metastasis (P < 0.0001), and the incidence of a negative expression of the c-kit protein increased as the number of the metastatic lymph nodes increased (P = 0.0003). The c-kit expression did not significantly correlate with the tumour size, nuclear grade, oestrogen receptor status, MIB-1 counts and p53 protein expression. A univariate analysis indicated the patients with the negative c-kit expression to have a worse disease-free survival (DFS) than those with the positive c-kit expression (P = 0.0041), while a multivariate analysis determined lymph node metastases and the MIB-1 counts to be independently significant factors for DFS. In conclusion, a loss of the c-kit expression was found in about three-fourth of invasive ductal carcinoma of the breast and was associated with lymph node metastases. The prognostic implications of the c-kit expression seem to be due to fact that a loss of the c-kit expression is associated with an advanced stage of breast cancer.}, } @article {pmid16711217, year = {2006}, author = {Shamir, A and Rubinstein, M and Levinboim, T}, title = {Generating comics from 3D interactive computer graphics.}, journal = {IEEE computer graphics and applications}, volume = {26}, number = {3}, pages = {53-61}, doi = {10.1109/mcg.2006.58}, pmid = {16711217}, issn = {0272-1716}, mesh = {*Art ; *Communication ; *Computer Graphics ; Imaging, Three-Dimensional/*methods ; *Narration ; *Software ; *User-Computer Interface ; }, } @article {pmid16708301, year = {2006}, author = {Tanase, H and Suda, K and Yamasaki, S and Nobukawa, B}, title = {Intraductal low papillary histological pattern of carcinoma component shows intraductal spread in invasive carcinoma of the pancreas.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {13}, number = {3}, pages = {235-238}, doi = {10.1007/s00534-005-1059-z}, pmid = {16708301}, issn = {0944-1166}, mesh = {Adult ; Aged ; Carcinoma in Situ/blood supply/*pathology ; Carcinoma, Pancreatic Ductal/blood supply/*pathology ; Carcinoma, Papillary/blood supply/*pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/blood supply/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND/PURPOSE: We attempted to discriminate between carcinoma in situ (CIS) and the intraductal invasion/cancerization of invasive ductal carcinoma (IDC) of the pancreas, by comparing the histological patterns of the intraductal components and those of venous invasion.

METHODS: Specimens from 30 patients with IDC were examined histopathologically. Intraductal components and blood vessel invasion in IDC were assessed in specimens stained with hematoxylin & eosin and elastica van Gieson (EVG).

RESULTS: Intraductal components of IDC were found in 28 of the 30 cases of IDC, in 261 ducts, and in 2.3 ducts per one section of one case, on average. The intraductal components of IDC were classified into three histological patterns, as follows: low papillary (including flat), tubular (including solid and cribriform), and mixed (low papillary plus tubular). The incidences of the low papillary, tubular, and mixed patterns in the 261 ducts, were 39% (102 ducts), 56% (145 ducts), and 5% (14 ducts), respectively. The histological pattern of venous invasion was tubular in all but 1 of the 26 cases, and this 1 case showed low papillary patterns as well as a tubular pattern.

CONCLUSIONS: A tubular pattern of intraductal components in IDC of the pancreas indicates intraductal invasion, while a low papillary pattern indicates CIS or carcinoma in another location to which it has spread.}, } @article {pmid16707453, year = {2006}, author = {Schuetz, CS and Bonin, M and Clare, SE and Nieselt, K and Sotlar, K and Walter, M and Fehm, T and Solomayer, E and Riess, O and Wallwiener, D and Kurek, R and Neubauer, HJ}, title = {Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis.}, journal = {Cancer research}, volume = {66}, number = {10}, pages = {5278-5286}, doi = {10.1158/0008-5472.CAN-05-4610}, pmid = {16707453}, issn = {0008-5472}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cell Movement/genetics ; Cluster Analysis ; Disease Progression ; Epithelial Cells/pathology ; Female ; Gene Amplification ; Gene Expression Profiling ; Humans ; Microdissection/methods ; Neoplasm Invasiveness ; Oligonucleotide Array Sequence Analysis ; Protein Biosynthesis/genetics ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Becoming invasive is a crucial step in breast cancer oncogenesis. At this point, a lesion carries the potential for spreading and metastasis--a process, whose molecular characteristics still remain poorly understood. In this article, we describe a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast ductal carcinomas to identify novel molecular markers characterizing the transition from DCIS to IDC. The purpose of this study was to better understand the molecular biology of this transition and to identify candidate genes whose products might serve as prognostic markers and/or as molecular targets for treatment. To obtain cellular-based gene expression profiles from epithelial tumor cells, we combined laser capture microdissection with a T7-based two-round RNA amplification and Affymetrix oligonucleotide microarray analysis. Altogether, a set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC and replicate DCIS/IDC preparations from three of the nine tumors. Cluster analysis on expression data shows the robustness and reproducibility of the techniques we established. Using multiple statistical methods, 546 significantly differentially expressed probe sets were identified. Eighteen candidate genes were evaluated by RT-PCR. Examples of genes already known to be associated with breast cancer invasion are BPAG1, LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C, SART2, and TNFAIP6 was localized to epithelial tumor cells by in situ hybridization and/or immunohistochemistry, confirming the accuracy of laser capture microdissection sampling and microarray analysis.}, } @article {pmid16703184, year = {2006}, author = {Crippa, S and Di Bella, C and Faravelli, A}, title = {Skin adnexal neoplasm closely resembling adenomatoid tumor: a unique occurrence.}, journal = {International journal of surgical pathology}, volume = {14}, number = {2}, pages = {177-178}, doi = {10.1177/106689690601400215}, pmid = {16703184}, issn = {1066-8969}, mesh = {Adenomatoid Tumor/pathology ; Adnexal Diseases/*pathology ; Aged ; Breast Neoplasms/surgery ; Carcinoma, Ductal/surgery ; Diagnosis, Differential ; Eccrine Glands/*pathology ; Female ; Humans ; Immunohistochemistry ; Neoplasms, Second Primary/*pathology ; Skin Neoplasms/metabolism/*pathology ; Thoracic Wall/*pathology ; }, abstract = {We describe a primary skin neoplasm located in the left chest wall that closely resembled adenomatoid tumor of male and female genital tract. It occurred in a 52-year-old woman who had undergone a left quadrantectomy with regional lymphadenectomy for invasive ductal carcinoma of the breast 7 years previously. The tumor involved the dermis and subcutaneous tissue and measured 0.7 cm in greatest diameter. Immunohistochemical evaluation showed strong positivity for cytokeratin pool and negativity for CD31, calretinin, WT-180, and for estrogen and progesterone receptors. We are unaware of a previous description of this morphologic pattern in a primary skin tumor, which we have interpreted as of skin adnexal and specifically of eccrine sweat gland origin.}, } @article {pmid16702952, year = {2006}, author = {Roylance, R and Gorman, P and Papior, T and Wan, YL and Ives, M and Watson, JE and Collins, C and Wortham, N and Langford, C and Fiegler, H and Carter, N and Gillett, C and Sasieni, P and Pinder, S and Hanby, A and Tomlinson, I}, title = {A comprehensive study of chromosome 16q in invasive ductal and lobular breast carcinoma using array CGH.}, journal = {Oncogene}, volume = {25}, number = {49}, pages = {6544-6553}, pmid = {16702952}, issn = {0950-9232}, support = {/WT_/Wellcome Trust/United Kingdom ; 077008/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; Chromosome Aberrations ; Chromosome Breakage ; *Chromosomes, Human, Pair 16 ; Cluster Analysis ; DNA, Neoplasm ; Gene Amplification ; Gene Deletion ; Genetic Linkage ; Humans ; Loss of Heterozygosity ; Models, Statistical ; Neoplasm Invasiveness/*genetics ; Neoplasm Staging ; Nucleic Acid Hybridization/*methods ; Tissue Array Analysis/*methods ; }, abstract = {We analysed chromosome 16q in 106 breast cancers using tiling-path array-comparative genomic hybridization (aCGH). About 80% of ductal cancers (IDCs) and all lobular cancers (ILCs) lost at least part of 16q. Grade I (GI) IDCs and ILCs often lost the whole chromosome arm. Grade II (GII) and grade III (GIII) IDCs showed less frequent whole-arm loss, but often had complex changes, typically small regions of gain together with larger regions of loss. The boundaries of gains/losses tended to cluster, common sites being 54.5-55.5 Mb and 57.4-58.8 Mb. Overall, the peak frequency of loss (83% cancers) occurred at 61.9-62.9 Mb. We also found several 'minimal' regions of loss/gain. However, no mutations in candidate genes (TRADD, CDH5, CDH8 and CDH11) were detected. Cluster analysis based on copy number changes identified a large group of cancers that had lost most of 16q, and two smaller groups (one with few changes, one with a tendency to show copy number gain). Although all morphological types occurred in each cluster group, IDCs (especially GII/GIII) were relatively overrepresented in the smaller groups. Cluster groups were not independently associated with survival. Use of tiling-path aCGH prompted re-evaluation of the hypothetical pathways of breast carcinogenesis. ILCs have the simplest changes on 16q and probably diverge from the IDC lineage close to the stage of 16q loss. Higher-grade IDCs probably develop from low-grade lesions in most cases, but there remains evidence that some GII/GIII IDCs arise without a GI precursor.}, } @article {pmid16698952, year = {2006}, author = {Lawson, JS and Tran, DD and Carpenter, E and Ford, CE and Rawlinson, WD and Whitaker, NJ and Delprado, W}, title = {Presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer.}, journal = {Journal of clinical pathology}, volume = {59}, number = {12}, pages = {1287-1292}, pmid = {16698952}, issn = {0021-9746}, mesh = {Animals ; Breast Neoplasms/pathology/*virology ; Carcinoma, Ductal, Breast/pathology/*virology ; Carcinoma, Intraductal, Noninfiltrating/pathology/*virology ; DNA, Viral/analysis ; Female ; Humans ; Mammary Neoplasms, Animal/pathology/virology ; Mammary Tumor Virus, Mouse/genetics/*isolation & purification ; Mice ; Mice, Inbred C3H ; Polymerase Chain Reaction/methods ; Retroviridae Infections/complications ; Tumor Virus Infections/complications ; Viral Envelope Proteins/analysis ; }, abstract = {BACKGROUND: Mouse mammary tumour virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. MMTV-like env gene sequences, which indicate the presence of a replication-competent MMTV-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. However, no evidence for a causal role of an MMTV-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological characteristics of human cancers and the presence of oncogenic viruses.

AIM: To investigate the possibility of an association between breast cancer and MMTV-like viruses.

METHODS: Histological characteristics of invasive ductal human breast cancer specimens were compared with archival MMTV-associated mammary tumours from C3H experimental mice. The presence of MMTV-like env DNA sequences in the human breast cancer specimens was determined by polymerase chain reaction and confirmed by Southern hybridisation.

RESULTS: MMTV-like env gene sequences were identified in 22 of 59 (37.3%) human breast cancer specimens. Seventeen of 43 (39.5%) invasive ductal carcinoma breast cancer specimens and 4 of 16 (25%) ductal carcinoma in situ specimens had some histological characteristics, which were similar to MMTV-associated mouse mammary tumours. However, these similarities were not associated with the presence or absence of MMTV-like gene sequences in the human breast tumour specimens. A significant (p = 0.05) correlation was found between the grade of the human breast cancer and similarity to the mouse mammary tumours. The lower the grade, the greater the similarity.

CONCLUSION: Some human breast cancer specimens, in which MMTV-like env DNA sequences have been identified, were shown to have histological characteristics (morphology) similar to MMTV-associated mouse mammary tumours. These observations are compatible with, but not conclusive of, an association between the presence of MMTV-like env DNA sequences and some human breast cancers.}, } @article {pmid16698674, year = {2006}, author = {Eigenbrod, S and Derwand, R and Jakl, V and Endres, S and Eigler, A}, title = {Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells.}, journal = {Immunological investigations}, volume = {35}, number = {2}, pages = {149-165}, doi = {10.1080/08820130600616490}, pmid = {16698674}, issn = {0882-0139}, mesh = {Apoptosis/immunology ; Cell Movement/*immunology ; Cell Survival/immunology ; Chemokines/immunology ; Dendritic Cells/cytology/enzymology/*immunology ; Endocytosis/immunology ; Humans ; Immunotherapy, Adoptive ; Lysophospholipids/*immunology/pharmacology ; Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/biosynthesis/*immunology/metabolism ; RNA, Messenger/biosynthesis/genetics ; Receptors, Lysosphingolipid/biosynthesis/genetics ; Sphingosine/*analogs & derivatives/immunology/pharmacology ; Statistics, Nonparametric ; }, abstract = {Dendritic cells (DC) are inducers of primary immune responses and represent an attractive vector for cancer immunotherapy. Sphingosine kinase (SphK) and its product sphingosine-1-phosphate (S1P) play an important role in the regulation of immune cells and cancer, affecting processes such as differentiation, growth or migration. We studied the role of SphK and S1P on migration of DC. RT-PCR showed mRNA expression of SphK in DC, declining from immature (iDC) to mature DC (mDC) to antigen-loaded mDC. Expression of S1P receptors was S1P(1) > S1P(2) = S1P(3), unrelated to maturation or antigen uptake. In transwell assays, iDC migrated towards SDF-1, MIP-1alpha, MCP and S1P, whereby S1P combined with a chemokine had a synergistic effect. mDC migrated towards 6Ckine and MIP-3beta, but not towards S1P. The SphK-inhibitor dihydro-sphingosine (DHS) reduced migration of iDC but not of mDC. In addition S1P(3)-inhibitor suramin inhibited DC migration in response to S1P. DHS had a reverse effect on endocytosis, enhancing the uptake of FITC dextran. We also observed an anti-apoptotic effect of S1P on mDC for the first time. This indicates that SphK/S1P may play a role in accumulation of peripheral iDC at the location of antigen and subsequent antigen-uptake. These findings may help to optimise DC-based cancer immunotherapy by modulation of SphK/S1P.}, } @article {pmid16685297, year = {2006}, author = {Hazza'a, AM and Albashaireh, ZS and Bataineh, A}, title = {The relationship of the inferior dental canal to the roots of impacted mandibular third molars in a Jordanian population.}, journal = {The journal of contemporary dental practice}, volume = {7}, number = {2}, pages = {71-78}, pmid = {16685297}, issn = {1526-3711}, mesh = {Adolescent ; Adult ; Age Distribution ; Female ; Humans ; Jordan ; Male ; Mandibular Nerve/*diagnostic imaging ; Molar, Third/*diagnostic imaging ; Radiography, Panoramic ; Sex Distribution ; Tooth Apex/*diagnostic imaging ; Tooth, Impacted/*diagnostic imaging/pathology ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the topographic relationship between the inferior dental canals (IDCs) and the roots of impacted mandibular third molars.

METHODS: Preoperative orthopantomograms (OPGs) were examined and the proximity of the IDC to the roots of impacted mandibular third molars was categorized into the following: groups: superimposition, adjacent, perforation, grooving, notching, or none. The categories notching, grooving, and perforation were regrouped together and called the true relationship between the IDC and the root apices. The type of impaction, age, and sex of the patient were also noted.

RESULTS: The positional category of 96.1% of the radiographs with bilateral impactions was identical on both sides of the mandible. Out of 2526 impacted mandibular third molars examined, 1146 (45.3%) belonged to the superimposition category, 663 (26.2%) were adjacent, 312 (12.3%) showed grooving, 78 (3.08%) showed notching, and 9 (0.35%) were actually perforating the IDC. The results showed 15.7% of the total cases were in true relationship with the IDC. There was a significant association (p = 0.000) between patient's age and true relationship.

CONCLUSIONS: Identical positional relationship of the bilateral impacted third molars to the IDC was noted in 96.1% of the radiographs. The position of the IDC in relation to the roots of impacted third molars varied according to the patient's age.}, } @article {pmid16684316, year = {2006}, author = {Duarte, GM and dos Santos, CC and Torresan, RZ and Alvarenga, M and Telles, GH and Bianchessi, ST and Caserta, N and Segala, SR and Lopes de Lima, Mda C and de Camargo Etchebehere, EC and Camargo, EE}, title = {Radioguided surgery using intravenous 99mTc sestamibi associated with breast magnetic resonance imaging for guidance of breast cancer resection.}, journal = {The breast journal}, volume = {12}, number = {3}, pages = {202-207}, doi = {10.1111/j.1075-122X.2006.00242.x}, pmid = {16684316}, issn = {1075-122X}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*surgery ; Feasibility Studies ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Minimally Invasive Surgical Procedures/*methods ; Radionuclide Imaging ; *Radiopharmaceuticals ; Surgery, Computer-Assisted/methods ; *Technetium Tc 99m Sestamibi ; Treatment Outcome ; }, abstract = {The purpose of this study was to evaluate the feasibility of surgery radioguided with intravenous (99m)Tc sestamibi associated with magnetic resonance imaging (MRI) of the breast to detect tumor extent and guide complete tumor resection. A descriptive experimental study was developed with 10 breast cancer patients (stage IIA-IIB) who underwent mastectomy. From 2 to 10 days before surgery, the patients underwent breast MRI with 0.1 mmol/kg of gadolinium and scintimammography with a 740 MBq of (99m)Tc sestamibi. A region of interest was drawn around the tumor image and an uptake curve as a function of time was plotted to calculate the optimal time to perform radioguided surgery. In the perioperative period, the same dose of (99m)Tc sestamibi was intravenously injected into the patients. Tumor resection was performed under the guidance of a gamma probe. MRI was used to evaluate the skin and deep fascia involvement and to detect occult tumor foci which were also excised. Subsequently a modified radical mastectomy was performed. Tumor and residual breast were histopathologically examined. In a series of 10 women, all demonstrated (99m)Tc sestamibi uptake in tumor cells. Eight patients showed no disease in the residual breast, one presented with one foci of invasive ductal carcinoma measuring 0.5 cm in diameter located 5 cm from the tumor bed, and one presented with one foci of ductal carcinoma in situ measuring 0.8 cm at the resection margin. The mean tumor size in the histopathologic assessment was 3.3 cm and in MRI was 5.0 cm. Radioguided surgery using (99m)Tc sestamibi associated with MRI is a feasible technique that can be employed in tumor resection.}, } @article {pmid16683225, year = {2006}, author = {Morrow, M and Keeney, K and Scholtens, D and Wei, J and Steel, J and Khan, SA}, title = {Selecting patients for breast-conserving therapy: the importance of lobular histology.}, journal = {Cancer}, volume = {106}, number = {12}, pages = {2563-2568}, doi = {10.1002/cncr.21921}, pmid = {16683225}, issn = {0008-543X}, mesh = {Adult ; Age Factors ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Case-Control Studies ; Contraindications ; Female ; Humans ; Magnetic Resonance Imaging ; Mammography ; *Mastectomy, Segmental/methods ; Middle Aged ; Neoplasm Recurrence, Local/prevention & control ; Neoplasm Staging ; *Patient Selection ; Regression Analysis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Concerns exist regarding the ability to select patients with lobular carcinoma for breast-conserving therapy (BCT) using mammography. The purpose of this study was to compare the conversion rate from BCT to mastectomy among patients with lobular (ILC) and ductal carcinoma (IDC), and to compare the number of resections needed to obtain negative margins.

METHODS: In all, 349 patients with pure or mixed ILC were identified from a database and 318 were successfully matched to 2 controls with IDC on the basis of year of diagnosis, menopausal status, and stage of disease. Conditional logistic regression was used to control for matching.

RESULTS: Patients with ILC were older, had larger tumors (2.6 vs. 2.1 cm; P<.001), and were more likely to have contraindications to BCT (25% vs. 20%). In patients thought to be candidates for BCT, no difference in success rate was noted on the basis of histologic type after controlling for age and stage. In those undergoing BCT, no difference in the number of procedures was seen on the bases of histology after adjustment for age and stage.

CONCLUSIONS: Patients with ILC are not more likely to fail BCT than those with IDC, nor do they require more operations to obtain negative margins. These results do not support the use of more extensive preoperative evaluation such as magnetic resonance imaging in patients with ILC.}, } @article {pmid16681686, year = {2006}, author = {Park, K and Han, S and Kim, HJ and Kim, J and Shin, E}, title = {HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry.}, journal = {Histopathology}, volume = {48}, number = {6}, pages = {702-707}, doi = {10.1111/j.1365-2559.2006.02403.x}, pmid = {16681686}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Male ; Middle Aged ; Receptor, ErbB-2/analysis/*genetics ; }, abstract = {AIM: To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC.

METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831).

CONCLUSION: Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.}, } @article {pmid16670630, year = {2006}, author = {Einama, T and Kagata, Y and Tsuda, H and Morita, D and Ogata, S and Ueda, S and Takigawa, T and Kawarabayashi, N and Fukatsu, K and Sugiura, Y and Matsubara, O and Hatsuse, K}, title = {High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome.}, journal = {Pancreas}, volume = {32}, number = {4}, pages = {376-381}, doi = {10.1097/01.mpa.0000220862.78248.c4}, pmid = {16670630}, issn = {1536-4828}, mesh = {Adenocarcinoma/mortality/*pathology ; Carcinoma, Pancreatic Ductal/mortality/*pathology ; Chromosomes, Human, Pair 5 ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/mortality/*pathology ; Prognosis ; S-Phase Kinase-Associated Proteins/*analysis/genetics ; Survival Rate ; }, abstract = {OBJECTIVES: Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma.

METHODS: Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise.

RESULTS: High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140).

CONCLUSIONS: It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.}, } @article {pmid16648106, year = {2006}, author = {Ruiz Tovar, J and Reguero Callejas, ME and Aláez Chillarón, AB and Ramiro Pérez, C and Collado Guirao, MV and Rojo Blanco, R and Muñoz Martín-Cámara, J and González-Palacios, F and García Villanueva, A}, title = {Mammary hamartoma.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {8}, number = {4}, pages = {290-293}, pmid = {16648106}, issn = {1699-048X}, mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Biopsy, Needle ; Breast Diseases/complications/diagnosis/diagnostic imaging/*pathology/surgery ; Breast Neoplasms/complications/diagnosis ; Carcinoma, Ductal, Breast/complications/diagnosis ; Female ; Hamartoma/complications/diagnosis/diagnostic imaging/*pathology/surgery ; Humans ; Mammography ; Middle Aged ; Recurrence ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {INTRODUCTION: Mammary hamartomas are rare benign breast lumps. They are usually painless, wellcircumscribed, mobile and with no adherence to skin or muscle, composed of varying amounts of fat, glandular and fibrous tissue. Mammary hamartoma has been classically considered as an underdiagnosed pathology, but with the increasing use of diagnostic procedures in breast tumours, the number of hamartomas has increased in the last years. Because there is no distinct pathological feature, a correlation with the clinical findings and image techniques is necessary in order to achieve a correct diagnosis of the pathology.

MATERIALS AND METHODS: The clinicopathological features of 8 mammary hamartomas are reported here.

RESULTS: The patients are ranged in age from 34 to 67 years. The initial manifestation was in all cases a well-circumscribed, soft, palpable breast lump. Mammography was performed in all patients. Other diagnostic procedures used in the diagnosis were Ultrasound, Fine Needle Aspiration Cytology and Needle Core Biopsy. Treatment was tumorectomy. We describe a case of recurrence after excision of the lump in a more aggressive histological form and one patient who presented the coexistence of a mammary hamartoma and an invasive ductal carcinoma.

CONCLUSION: Mammary hamartoma is an uncommon breast tumour. It is necessary the correlation between pathology and clinical and radiological findings. We express our management plan for these lesions.}, } @article {pmid16647957, year = {2006}, author = {Strauss, BL and Bratthauer, GL and Tavassoli, FA}, title = {STAT 5a expression in the breast is maintained in secretory carcinoma, in contrast to other histologic types.}, journal = {Human pathology}, volume = {37}, number = {5}, pages = {586-592}, doi = {10.1016/j.humpath.2006.01.009}, pmid = {16647957}, issn = {0046-8177}, mesh = {Adenocarcinoma/*metabolism/pathology ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; STAT5 Transcription Factor/*metabolism ; Tumor Suppressor Proteins ; }, abstract = {The 7 signal transducer and activator of transcription (STAT) molecules are responsible for the transcription of a variety of regulatory and differentiation proteins. STAT 5a is activated through a variety of mechanisms; in the breast, this is predominantly through binding of prolactin to its receptor. Previously, we showed that STAT 5a expression is decreased in atypical and malignant breast ductal epithelial cells. Interestingly, STAT 5a overexpression was observed in cells undergoing secretory change. In this study, secretory carcinomas were examined by immunohistochemistry for the presence of STAT 5a. In contrast to usual in situ or invasive ductal carcinoma, which lacked STAT 5a expression, all secretory carcinomas (11 invasive and 7 in situ, including 4 cases with both) expressed STAT 5a. No expression was seen in apocrine metaplasia or in other specialized breast carcinomas, such as mucinous or clear cell carcinoma. This retention of signal in the secretory carcinomas may be explained by the higher STAT 5a concentration present in cells undergoing secretory changes in general. Alternatively, STAT 5a expression may be related to the t(12;15)(p13;q25) chromosomal translocation, associated with certain pediatric tumors and recently demonstrated in many secretory carcinomas of the breast, which results in the expression of a tyrosine kinase through ETV6 and NTRK3 fusion. ETV6 also has been associated with the STAT 5a signaling pathway in another gene translocation and may be altering STAT 5a expression in secretory carcinomas. Breast cancer causes significant morbidity and mortality, and, regardless of the mechanism for retention of STAT 5a expression in this uncommon variant, the examination of STAT 5a will aid our understanding of normal and abnormal breast tissues.}, } @article {pmid16645950, year = {2006}, author = {Neubauer, H and Clare, SE and Kurek, R and Fehm, T and Wallwiener, D and Sotlar, K and Nordheim, A and Wozny, W and Schwall, GP and Poznanović, S and Sastri, C and Hunzinger, C and Stegmann, W and Schrattenholz, A and Cahill, MA}, title = {Breast cancer proteomics by laser capture microdissection, sample pooling, 54-cm IPG IEF, and differential iodine radioisotope detection.}, journal = {Electrophoresis}, volume = {27}, number = {9}, pages = {1840-1852}, doi = {10.1002/elps.200500739}, pmid = {16645950}, issn = {0173-0835}, mesh = {Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/*chemistry/drug therapy/genetics ; Cell Extracts/chemistry ; Cryopreservation ; Drug Resistance, Neoplasm ; Electrophoresis, Gel, Two-Dimensional/*methods ; Female ; Humans ; Hydrogen-Ion Concentration ; Iodine Radioisotopes/analysis ; *Lasers ; Microdissection/*methods ; Mutation ; Neoplasm Proteins/*analysis ; Proteomics/*methods ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Tamoxifen/therapeutic use ; }, abstract = {The presence of progesterone receptor (PR) in estrogen receptor (ER)-positive breast cancer is associated with a good prognosis, and indicates that tumors are likely to respond to tamoxifen. However, ER+/PR- tumors respond less well. To reveal the potential molecular mechanism of this phenomenon, we sought to identify differential protein abundances between invasive ductal carcinoma cells from cryopreserved ER+/PR+ and ER+/PR- mammary tumor specimens. Because current proteomics methods are hampered in the examination of most primary human tumor samples by the extreme tissue heterogeneity, we used laser capture microdissection (LCM) to isolate tumor cells and developed a sample pooling strategy to analyze small sample protein lysates. Proteins from LCM-harvested tumors were pooled into four sub-pools from each condition of three tumors/sub-pool, and proteins from respective paired sub-pools were co-electrophoresed by 2-DE using 54-cm IEF over pH 4-9. Abundance ratios were accurately quantified by a differential multiplex radioactive ProteoTope method at low attomole levels (approximately 3.6 microg protein per labeling reaction, <180 ng per multiplex protein sample per 54-cm gel). Applying this approach, differentially displayed proteins were identified by MS using comigrating non-radioactively labeled tumor proteins. They include decreased cytochrome b5 and transgelin, and more abundant CRABP-II, cyclophilin A, Neudesin, and hemoglobin in ER+/PR+ tumors versus ER+/PR- providing a possible explanation for differential susceptibility against tamoxifen as a result of deregulated cytochrome b5-dependent metabolism. This study demonstrates the potential of ProteoTope and LCM to enable extremely sensitive and precise differential analyses from well-defined primary clinical specimen.}, } @article {pmid16642558, year = {2006}, author = {Kim, YJ and Shim, HS and Lee, H and Jung, WH}, title = {Metaplastic carcinoma with extensive chondroid differentiation in the breast (chondroid carcinoma).}, journal = {Yonsei medical journal}, volume = {47}, number = {2}, pages = {259-263}, pmid = {16642558}, issn = {0513-5796}, mesh = {Actins/metabolism ; Antigens, CD34/biosynthesis ; Breast Neoplasms/complications/metabolism/*pathology ; Carcinoma/*complications/metabolism/pathology ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; Keratins/metabolism ; Metaplasia ; Middle Aged ; Mucin-1/metabolism ; Muscle, Smooth/pathology ; Neoplasm Metastasis ; S100 Proteins/chemistry ; }, abstract = {Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.}, } @article {pmid16631754, year = {2006}, author = {Celis, JE and Gromova, I and Gromov, P and Moreira, JM and Cabezón, T and Friis, E and Rank, F}, title = {Molecular pathology of breast apocrine carcinomas: a protein expression signature specific for benign apocrine metaplasia.}, journal = {FEBS letters}, volume = {580}, number = {12}, pages = {2935-2944}, doi = {10.1016/j.febslet.2006.03.080}, pmid = {16631754}, issn = {0014-5793}, mesh = {Apocrine Glands/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Neoplasm Proteins/*metabolism ; }, abstract = {Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.}, } @article {pmid16628084, year = {2006}, author = {Shimada, K and Sakamoto, Y and Sano, T and Kosuge, T and Hiraoka, N}, title = {Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: a clinicopathologic comparison with a common type of invasive ductal carcinoma.}, journal = {Pancreas}, volume = {32}, number = {3}, pages = {281-287}, doi = {10.1097/01.mpa.0000202955.33483.e2}, pmid = {16628084}, issn = {1536-4828}, mesh = {Adenocarcinoma, Mucinous/*pathology ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; Liver Neoplasms/secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*pathology ; }, abstract = {OBJECTIVES: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an indolent neoplasm by nature; however, it sometimes acquires invasive potential and has been classified as invasive IPMN. The aim of the present study was to investigate the clinicopathologic difference between invasive IPMN and a common type of invasive ductal carcinoma of the pancreas.

METHODS: Eighteen patients with invasive IPMN underwent pancreatectomy between 1992 and 2004. Clinical, biochemical, and histopathologic factors were retrospectively analyzed. The resulting data were compared with those of 274 patients with a common type of pancreatic ductal carcinoma who underwent surgery during the same period.

RESULTS: The total size of tumor of invasive IPMN, including cystic and invasive components, was statistically larger than that of a common type of invasive ductal carcinoma (62 vs 40 mm, P < 0.001), but the size of invasive component of invasive IPMN was smaller than that of a common type of invasive ductal carcinoma (21 vs 40 mm, P < 0.001). Negative lymph node metastases and relatively limited local tumor spreading were frequently observed in patients with invasive IPMN. On microscopic examination, the tumors infiltrating the surrounding tissue had a less invasive growth pattern, and a lower frequency of lymphatic invasion, venous invasion, and intrapancreatic neural invasion was also observed in patients with invasive IPMN. The 5-year survival rate of invasive IPMN was significantly higher than that of common-type invasive ductal carcinoma (42% vs 20%, P = 0.04).

CONCLUSIONS: An increased awareness of invasive IPMN has enabled pancreatectomies to be performed at an earlier stage, relative to that for ordinary pancreatic cancer. The less frequent detection of pathological factors concerned with tumor invasiveness in patients with invasive IPMN suggested the lower aggressive behavior of this tumor.}, } @article {pmid16627986, year = {2006}, author = {Zhong, D and Morikawa, A and Guo, L and Colpaert, C and Xiong, L and Nassar, A and Chen, C and Lamb, N and Dong, JT and Zhou, W}, title = {Homozygous deletion of SMAD4 in breast cancer cell lines and invasive ductal carcinomas.}, journal = {Cancer biology & therapy}, volume = {5}, number = {6}, pages = {601-607}, doi = {10.4161/cbt.5.6.2660}, pmid = {16627986}, issn = {1538-4047}, mesh = {Base Sequence ; Breast Neoplasms/*genetics ; Carcinoma, Ductal/*genetics/pathology ; Cell Line, Tumor ; DNA Primers ; Female ; *Gene Deletion ; Homozygote ; Humans ; Neoplasm Invasiveness ; Smad4 Protein/*genetics ; }, abstract = {Inactivation of TGF-beta/SMAD4 signaling was postulated to play an important role in breast cancer development. Even though SMAD4 is located on 18q21, a region frequently lost in breast cancers, point mutations of SMAD4 were rarely observed, implying that biallelic inactivation of SMAD4 was not necessary in the process. In this study, a novel homozygous deletion of SMAD4 was identified in breast cancer cell line SW527 during a screening of 31 breast cancer cell lines. As several breast cancer cell lines were shown to contain SMAD4 homozygous deletion, we sought to develop a reliable method to access such lesions in archived primary tumor specimens. First, a DNA quantification method was developed to measure as few as 5 copies of DNA templates so that the amount of genomic DNA isolated by laser-capture microdissection can be accurately determined. Next, accurate DNA quantitation allowed sufficient DNA templates to be included in the homozygous deletion assay for the robust amplification of SMAD4 genetic markers. Two out of 24 primary infiltrative ductal carcinomas (IDC) with 18q allelic imbalance were determined to contain SMAD4 homozygous deletions, and these samples are also negative for Smad4 protein expression by immunohistochemistry. Our data suggest that biallelic inactivation of SMAD4 through homozygous deletion does occur in a small percentage of IDCs, and support the hypothesis that inactivation of TGF-beta/SMAD4 signaling plays in a role in the development of a subset of IDC.}, } @article {pmid16627391, year = {2006}, author = {Bergenstal, RM}, title = {Treatment models from the International Diabetes Center: advancing from oral agents to insulin therapy in type 2 diabetes.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {12 Suppl 1}, number = {}, pages = {98-104}, doi = {10.4158/EP.12.S1.98}, pmid = {16627391}, issn = {1530-891X}, mesh = {Algorithms ; Behavior Therapy ; Cost-Benefit Analysis ; Diabetes Mellitus, Type 2/*drug therapy/economics/therapy ; Humans ; Hypoglycemic Agents/*therapeutic use ; Insulin/adverse effects/*therapeutic use ; Patient Care Team ; Patient Education as Topic/methods ; }, abstract = {OBJECTIVE: To discuss treatment models used at the International Diabetes Center (IDC) and present strategies for transitioning patients with type 2 diabetes from orally administered medications to insulin therapy.

METHODS: The experiences of the IDC in developing and improving patient care and educational programs are reviewed. In addition, clinical outcomes and economic results are highlighted.

RESULTS: In the management of chronic conditions such as diabetes, the patient is a crucial member of the health-care team. Therefore, patients must understand and endorse treatment goals. Key components of the patient-centered IDC treatment model are group instruction focused on behavioral change, worksite education and coaching programs, and treatment algorithms to help clinicians identify treatment priorities and initiate appropriate therapeutic strategies, including early and more effective use of insulin therapy.

CONCLUSION: The IDC patient-centered team model aimed at helping patients live well with diabetes has been shown to improve achievement of glycemic, lipid, and blood pressure goals, and it is economically viable. One approach to helping more patients with type 2 diabetes reach glycemic targets is for clinicians to become more comfortable with, and therefore more aggressive in, initiating and adjusting insulin therapy.}, } @article {pmid16627203, year = {2006}, author = {Kuzmiak, CM and Dancel, R and Pisano, E and Zeng, D and Cole, E and Koomen, MA and McLelland, R}, title = {Consensus review: A method of assessment of calcifications that appropriately undergo a six-month follow-up.}, journal = {Academic radiology}, volume = {13}, number = {5}, pages = {621-629}, doi = {10.1016/j.acra.2006.01.042}, pmid = {16627203}, issn = {1076-6332}, mesh = {Breast Diseases/diagnostic imaging/epidemiology ; Breast Neoplasms/*diagnostic imaging/*epidemiology ; Calcinosis/*diagnostic imaging/*epidemiology ; *Consensus ; Female ; Humans ; Incidence ; Mammography/*statistics & numerical data ; Outcome Assessment, Health Care/methods ; Precancerous Conditions/diagnostic imaging/epidemiology ; Prognosis ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors ; Severity of Illness Index ; United States/epidemiology ; }, abstract = {RATIONALE AND OBJECTIVES: Breast calcifications seen on mammography may be associated with benign conditions or malignancies. Accurate characterization of these calcifications is crucial to providing optimal care that may spare women unnecessary biopsies and appropriately allow interval mammography. The purpose of this study is to determine if consensus characterization of calcifications by two breast imaging experts using standardized criteria can establish that follow-up is a safe option.

MATERIALS AND METHODS: For this retrospective study, our breast imaging database was reviewed and the cases imaged between the years 1999 and 2001 were used to identify patients with calcifications who were recommended for a six-month follow-up or biopsy. All cases had been prospectively assessed by at least two expert breast imagers using standardized features to assess the findings before a recommendation for follow-up or a biopsy was made. A retrospective chart review examining the radiology reports was done to determine the percentage of women from each of the two groups who developed malignancies.

RESULTS: Of 744 patients who had mammographically identified clusters of calcifications, 490 clusters (409 single and 81 multiple) were diagnosed as probably-benign, and a short-interval 6-month follow-up was recommended. Of these calcifications followed for three years, only two (0.5%) of the single clusters proved to be malignant, and malignancy was diagnosed at the 12-month follow-up examination. In both cases, the women were diagnosed with ductal carcinoma in situ (DCIS). Of 254 clusters recommended for biopsy, 242 (215 single and 27 multiple) underwent biopsy. A total of 70 cancers were diagnosed: 54 (77.1%) were DCIS and 16 (22.9%) were primary invasive mammary carcinoma (10 cases of invasive ductal carcinoma, 3 cases of invasive lobular carcinoma, 2 cases of invasive ductal carcinoma with DCIS, and one case of invasive mucinous carcinoma with DCIS). Twenty-nine percent of women who had a biopsy performed had calcifications associated with malignancy. In contrast, in the women whose calcifications were followed by mammography, only 0.5% went on to develop malignancies.

CONCLUSION: Consensus review of calcifications by two breast imagers using standardized criteria is a safe follow-up option.}, } @article {pmid16626574, year = {2006}, author = {Huang, RC and Yao, K and Li, YL and Zhang, YQ and Xu, SK and Shi, HY and Pan, CZ and Yang, S and Zhang, SH and Ge, L and Niu, YH and Zhang, F and Qian, JY and Zou, YZ and Ge, JB}, title = {[Transplantation of autologous bone marrow mononuclear cells on patients with idiopathic dilated cardiomyopathy: early results on effect and security].}, journal = {Zhonghua xin xue guan bing za zhi}, volume = {34}, number = {2}, pages = {111-113}, pmid = {16626574}, issn = {0253-3758}, mesh = {*Bone Marrow Transplantation ; Cardiomyopathy, Dilated/surgery/*therapy ; Humans ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {OBJECTIVE: The aim of this study is to identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy (IDC) patients who were treated by intracoronary transplantation of autologous mononuclear bone marrow cells (BMCs) in addition to standard therapy.

METHODS: Based on given standard therapy, eighteen patients with idiopathic dilated cardiomyopathy were enrolled and divided into transplantation group and control group. The clinical characteristics of two groups were comparable. Among these patients, 10 patients were performed percutaneous coronary autologous BMCs transplantation. Blood routine test, hepatic function, renal function, glucose, triglyceride (TG), cholesterol, low density cholesterol (LDL), high density cholesterol (HDL), uric acid (UA) and high sensitive C-reactive protein (hsCRP) were measured at the time point of pre-operation and some time after transplantation. All patients were monitored under ultrasonic cardiography, Holter, six-minute-walk test and magnetic resonance imaging over a period of at least 6 months. Annual hospital days were recorded during two-year follow-up.

RESULTS: Blood routine test, hepatic function, renal function, glucose, TG, cholesterol, LDL, HDL, UA and hsCRP had no significant differences among 48 hours, 3 months and 6 months after transplantation compared with control and pre-transplantation (P > 0.05). Six-minute-walk distance elevated significantly six months after BMCs transplantation compared with control and pre-transplantation [(494.3 +/- 62.8) m vs (307.2 +/- 75.0) m, (321.5 +/- 63.7) m, P < 0.05]. Left ventricular ejection fraction (LVEF) and the sizes of LVEDd had no significant changes compared with that of control and pre-transplantation (P > 0.05). Myocardium lesion area measured by (MRI) seemed decrease in transplantation group compared with that of control and pre-operation [(4.96 +/- 0.47) cm(2) vs (5.12 +/- 0.54) cm(2), (5.02 +/- 0.39) cm(2), P > 0.05], but there was no significance. None of proarrhythmias and side effects had been observed around transplantation and 2 years follow-up. There was no significant difference in survival between two groups in 2 years follow-up. Interestingly, annual hospital day in BMCs transplantation patients was significantly shorter than that in control group [(30.2 +/- 11.2) d vs (43.6 +/- 9.8) d, P < 0.05].

CONCLUSIONS: Autologous bone marrow mononuclear cells transplantation can prolong six-minute-walk, decrease re-hospitalization rate, elevate exercise ability and help to improve cardiac function in patients with IDC. In addition, it was demonstrated that cell transplantation is safe.}, } @article {pmid16619588, year = {2006}, author = {Kourea, HP and Koutras, AK and Zolota, V and Grimani, I and Tzoracoeleftherakis, E and Koukouras, D and Fountzilas, G and Gogas, H and Kyriakou, K and Adamou, A and Kalofonos, HP}, title = {Expression of p27KIP1, p21WAF1 and p53 does not correlate with prognosis in node-negative invasive ductal carcinoma of the breast.}, journal = {Anticancer research}, volume = {26}, number = {2B}, pages = {1657-1668}, pmid = {16619588}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Nucleus/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/*biosynthesis ; Cyclin-Dependent Kinase Inhibitor p27/*biosynthesis ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {The expressions ofp27Kip1 (p27) and p21waf1 (p21) cyclin-dependent kinase inhibitors and p53 were examined in a series of 170 node-negative breast carcinomas (NNBCs) to evaluate their prognostic significance. Low nuclear (p27TN) and cytoplasmic (p27TC) p27 expressions were noted in 66% and 81% of NNBCs, respectively. p21 and p53 overexpressions were detected in 56% and 26%, respectively. Low p27TN was significantly associated with high grade (p=0.001), age < or = 50 years (p=0.01), negative hormone receptors (p<0.001), low p27TC (p<0.001) and p53 overexpression (p=0.02). Low p27TC was associated with negative hormone receptors (p<0.001). p53 overexpression was associated with high grade (p<0.001) and negative hormone receptors (p<0.001). p21 overexpression, although not correlated with the examined parameters, was associated with increased disease-free survival in univariate analysis. In multivariate analysis, p27TN, p27TC, p21 and p53 were not associated with disease-free survival or overall survival. These findings argue against the prognostic value of p27, p21 and p53 in NNBC.}, } @article {pmid16619488, year = {2006}, author = {Seth, RM and Burger, AM and Kahn, HJ}, title = {Analysis of the HER2/neu gene amplification in microdissected breast cancer tumour samples.}, journal = {Anticancer research}, volume = {26}, number = {2A}, pages = {927-931}, pmid = {16619488}, issn = {0250-7005}, mesh = {Base Sequence ; Breast Neoplasms/*genetics/metabolism/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; Microdissection ; Molecular Sequence Data ; Polymerase Chain Reaction ; Receptor, ErbB-2/biosynthesis/genetics ; }, abstract = {The HER2/neu oncogene has been reported to be amplified in > 20% of invasive ductal carcinomas. In order to investigate the HER2/neu status in pure populations of breast cancer cells, a laser capture microdissection (LCM) system was used. Formalin-fixed paraffin-embedded breast tissue areas corresponding to normal ducts, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were microdissected and genomic DNA was isolated by a modified proteinase K- phenol extraction method and subjected to PCR for HER2/neu analysis. One hundred % concordance for detection of the HER2/neu gene amplification was found between immunohistochemistry and PCR used in combination with LCM. Our results indicated that LCM is a powerful technique for isolating pure populations of cells from paraffin-embedded tissue sections and that these cells can be used to study genomic alterations at the DNA level.}, } @article {pmid16615151, year = {2006}, author = {Tani, M and Kawai, M and Terasawa, H and Ina, S and Hirono, S and Uchiyama, K and Yamaue, H}, title = {Does postoperative chemotherapy have a survival benefit for patients with pancreatic cancer?.}, journal = {Journal of surgical oncology}, volume = {93}, number = {6}, pages = {485-490}, doi = {10.1002/jso.20440}, pmid = {16615151}, issn = {0022-4790}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/mortality/pathology/surgery ; Combined Modality Therapy ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage ; Humans ; Infusions, Intra-Arterial ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatectomy/*mortality ; Pancreatic Neoplasms/*drug therapy/mortality/pathology/surgery ; Postoperative Care ; Survival Rate ; Gemcitabine ; }, abstract = {In our study, we investigated whether postoperative chemotherapy improved survival in patients with invasive ductal carcinoma of the pancreas. Between 1987 and 2004, 111 patients underwent pancreatic resection against invasive ductal carcinoma of the pancreas in Wakayama Medical University Hospital. Median survival time (MST) was 19.4 months, 8.6 months, and 7.2 months, in JPS Stage III (UICC Stage IIA and IIB), JPS Stage IVa (UICC Stage IIA and IIB), and JPS Stage IVb (UICC Stage IV), respectively (P < 0.01). The MST of the chemotherapy group was 12 months, and the MST of the non-chemotherapy group was 8.4 months (P < 0.05). Moreover, in JPS Stage IV (UICC Stage IIA, IIB, III, and IV) highly advanced pancreatic cancer, the MST of the chemotherapy group was 10.9 months, and the MST of the group without chemotherapy was 6.6 months (P < 0.01). Since pancreatic cancer is characterized by an aggressive tumor with a high recurrent rate, postoperative chemotherapy is effective for an improvement of survival.}, } @article {pmid16614520, year = {2006}, author = {Lee, MJ and Suh, CH and Li, ZH}, title = {Clinicopathological significance of maspin expression in breast cancer.}, journal = {Journal of Korean medical science}, volume = {21}, number = {2}, pages = {309-314}, pmid = {16614520}, issn = {1011-8934}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/mortality/pathology ; DNA, Neoplasm/analysis/genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Ploidies ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Serpins/*metabolism ; Survival Rate ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype.}, } @article {pmid16613340, year = {2006}, author = {Qureshi, HS and Linden, MD and Divine, G and Raju, UB}, title = {E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters.}, journal = {American journal of clinical pathology}, volume = {125}, number = {3}, pages = {377-385}, pmid = {16613340}, issn = {0002-9173}, mesh = {Adenocarcinoma/classification/*metabolism/pathology ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/classification/*metabolism/*pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/classification/metabolism/pathology ; Carcinoma, Lobular/classification/metabolism/pathology ; Cell Count ; Female ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Staging ; Prognosis ; Sensitivity and Specificity ; }, abstract = {Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or a predictor of prognosis. We stained 276 breast carcinomas with monoclonal antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type, 9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%; EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while cords were negative. Statistically a correlation of EC loss with a positive diagnosis of ILC was found but there was no correlation with any prognostic tumor variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%; negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value, 91.2%). EC is helpful in classifying cases with indeterminate histologic features. EC loss is uncommon in nonlobular carcinomas with no correlation to currently established prognostic variables.}, } @article {pmid16610682, year = {2006}, author = {Robles-Frías, A and González-Cámpora, R and Martínez-Parra, D and Robles-Frías, MJ and Vázquez-Cerezuela, T and Otal-Salaverri, C and Almeida-González, C}, title = {Robinson cytologic grading in invasive ductal carcinoma of the breast: correlation with E-cadherin and alpha-, beta- and gamma-catenin expression and regional lymph node metastasis.}, journal = {Acta cytologica}, volume = {50}, number = {2}, pages = {151-157}, doi = {10.1159/000325924}, pmid = {16610682}, issn = {0001-5547}, mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/*diagnosis/pathology ; Cadherins/*biosynthesis ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Sensitivity and Specificity ; Staining and Labeling ; alpha Catenin/*biosynthesis ; beta Catenin/*biosynthesis ; gamma Catenin/*biosynthesis ; }, abstract = {OBJECTIVE: To correlate the cytologic grade of breast carcinoma with the expression of E-cadherin/catenin system molecules and the presence of metastasis in regional lymph nodes.

STUDY DESIGN: Aspirate smears were examined together with histologic sections from the corresponding neoplasms taken from 100 patients with invasive ductal carcinoma. In 50 cases, > or = 1 metastatic nodes were identified. Cytologic grading of the smears was performed using the Robinson method. Immunohistochemical expression of E-cadherin and of alpha-, beta- and gamma-catenin was studied.

RESULTS: A statistically significant relationship was observed between E-cadherin/catenin expression and cytologic grade (p < 0.0005). This association was particularly relevant to the cell dissociation parameter (p < 0.0005).

CONCLUSION: The cytological grade established in preoperative studies may provide relevant information on the aggressiveness of invasive ductal carcinoma and its tendency to produce regional metastasis. This finding could be particularly useful in cases of breast carcinoma in which neoadjuvant therapy is the method of choice.}, } @article {pmid16606540, year = {2006}, author = {Niu, Y and Wang, Y and Yu, Y and Ding, XM and Lü, SH and Xiao, XQ}, title = {[Expression of alpha-tubulin and gamma-tubulin in premalignant lesion and carcinoma of breast and the significance thereof].}, journal = {Zhonghua yi xue za zhi}, volume = {86}, number = {1}, pages = {56-60}, pmid = {16606540}, issn = {0376-2491}, mesh = {Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Centrosome/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Precancerous Conditions/genetics/metabolism/*pathology ; RNA, Messenger/genetics/metabolism ; Survival Analysis ; Tubulin/genetics/*metabolism ; }, abstract = {OBJECTIVE: To investigate the expression of alpha-tubulin and gamma-tubulin, 2 kinds of centrosome proteins, in premalignant lesion and carcinoma of breast and the significance thereof.

METHODS: Forty specimens of premalignant lesions of breast, 40 specimens of infiltrating ductal carcinoma of breast, 40 specimens of intraductal carcinoma (IDC), and 30 specimens of normal breast tissues were obtained during operation. Immunohistochemistry was used to analyze the protein expression of alpha-tubulin and gamma-tubulin, and the percentages of ki67 positive cells. Western blotting was used to examine the mRNA expression of alpha-tubulin and gamma-tubulin.

RESULTS: The protein and mRNA expression values of alpha-tubulin and gamma-tubulin in breast carcinoma were higher than those in the premalignant lesions and normal breast tissues with significant differences between the premalignant lesions and normal breast torques and without significant differences between infiltrating ductal carcinoma of breast and IDC. The ki67 positive rates of the infiltrating ductal carcinoma of breast group, IDC group, premalignant lesion group, and normal breast tissues group were 16.0%, 37.0%, 53.6%, and 67.8% (P = 0.001). A positive correlation existed between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P = 0.00) and there was no significant correlation between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P > 0.05). Both the expression of alpha-tubulin and the expression of gamma-tubulin were significantly associated with the prognosis.

CONCLUSIONS: Centrosome protein is one of the distinct phenotypes of breast cancer cells. Aberration of centrosome proteins may be used to screen high risk cases of breast carcinoma and to estimate the prognosis.}, } @article {pmid16604511, year = {2006}, author = {Larson, PS and de las Morenas, A and Cerda, SR and Bennett, SR and Cupples, LA and Rosenberg, CL}, title = {Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors.}, journal = {The Journal of pathology}, volume = {209}, number = {3}, pages = {307-316}, doi = {10.1002/path.1973}, pmid = {16604511}, issn = {0022-3417}, support = {CA81078/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; *Allelic Imbalance ; Breast/*pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Humans ; Hyperplasia/genetics ; Microdissection ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction/methods ; Precancerous Conditions/*genetics ; }, abstract = {It remains unclear whether hyperplastic breast lesions, especially with atypia, are cancer precursors or markers of increased cancer risk. Quantified comparisons of genomic alterations in coexisting lesions could address this question. Therefore, we examined allele imbalance (AI), also known as loss of heterozygosity (LOH), at 20 microsatellite markers on nine chromosome arms, in DNA from 106 samples microdissected from 17 randomly selected cancer-containing breast specimens: 13 simple (DH) and 45 atypical ductal hyperplastic (ADH) lesions, 30 in situ (DCIS) and 18 invasive ductal carcinomas (IDC). Data were analysed using regression models and generalized estimating equations. We found that AI increased as histology became more aberrant and varied with histology across the chromosome arms (p<0.0001). ADH had more AIs on 1q (p=0.03) and 16q (p=0.02) and fewer AIs on 17p (p=0.06) and 17q (p<0.0001) than on other arms. In cancers, AIs remained high on 1q and 16q, and became frequent on 17p and 17q. Concordance between AIs in ADHs and cancers exceeded the 50% expected if the lesions were separate clones in 16/20 (80%) ADHs (p=0.05), from 9/11 (82%) cases (p=0.03), and involved 41/51 (80%) evaluable markers (p=0.05). The occurrence of any AI in ADH predicted greater AI (p=0.009) and possibly lower grade (p=0.05) in coexisting cancers. Nevertheless, ADHs were not genetically identical to cancers or to each other. We found AIs discordant between ADHs and cancers (always on 1q and 16q), AIs unique to ADH (usually on 11q) and some genetic heterogeneity among coexisting ADHs. We conclude that ADH lesions are genetically advanced, with frequent alterations on 1q and 16q, and are often direct cancer precursors. Their global genetic characteristics predict features of cancers in the same breast. Nevertheless, the genetic heterogeneity detected suggests that hyperplasias and cancers may arise on a field at generalized increased cancer risk.}, } @article {pmid16604497, year = {2006}, author = {Liu, W and Li, WM and Gao, C and Li, Y and Kong, YH}, title = {[The research on associating the single nucleotide polymorphism of CTLA-4 gene promoter region with idiopathic dilated cardiomyopathy].}, journal = {Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics}, volume = {23}, number = {2}, pages = {198-201}, pmid = {16604497}, issn = {1003-9406}, mesh = {Antigens, CD/*genetics ; CTLA-4 Antigen ; Cardiomyopathy, Dilated/*genetics ; Female ; Haplotypes ; Humans ; Male ; *Polymorphism, Single Nucleotide ; Promoter Regions, Genetic/*genetics ; }, abstract = {OBJECTIVE: To investigate the expression of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in patients with idiopathic dilated cardiomyopathy (IDC) and to explore genetic susceptibility to IDC caused possibly by single nucleotide polymorphism (SNP) of CTLA-4 gene promoter.

METHODS: PCR-restriction fragment length polymorphism techniques were used to analyze the SNPs of CTLA-4 gene at position -1772, -1661 and -318 in the promoter region. Serum sCTLA-4, IFN-gamma and IL-4 were tested by ELISA.

RESULTS: sCTLA-4 levels of IDC patients were associated with the haplotype and genotype. Patients with -1772 TC genotype or -1772 TC -1661 AA, -1772 TC -1661 AG haplotypes had higher sCTLA-4 levels than patients with other haplotypes did. The frequency of -1772 TC genotype was significantly high in patients with low ejection factor(EF) values. Whereas the frequencies of -1661 G allele and -1661 GG genotype were lower in IDC patients. Levels of IL-4 were increased in IDC group.

CONCLUSION: Patients with IDC have an aberrant expression of the CTLA-4 products, and the -1772 C/T and -1661 A/G polymorphisms. The two SNPs may function as genetic markers for disease susceptibility.}, } @article {pmid16598321, year = {2006}, author = {Hussain, SS and Qattan, AT and Nirmal, MS and Al-Malik, OA and Al-Tweigeri, TA and Tulba, AM and Bin Amer, SM}, title = {Gene expression profiles of the fibroblasts from breast tumors and normal tissue compared with the tumor expression profiles.}, journal = {Saudi medical journal}, volume = {27}, number = {4}, pages = {463-469}, pmid = {16598321}, issn = {0379-5284}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Case-Control Studies ; Female ; Fibroblasts/*physiology ; Gene Expression Profiling ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; }, abstract = {OBJECTIVE: The study was designed to examine whether the gene expression profiles of fibroblast cell lines, established from the tumor and the normal tissue from the same breast, exhibit any similarities with the profiles of the original tissues.

METHODS: Fibroblast cell lines were established from invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) of the breast and the adjacent normal tissues. Isolated total RNA from the cell lines and tissues were used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas microarrays for obtaining profiles of expressed genes. The profiles of tumors and cell lines were compared. This study was carried out at King Faisal specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and 2005.

RESULTS: Alterations of expression of most of the genes in the tissues were not detectable in the cell lines. The expression of a lower number of genes was altered in DCIS compared with that in IDC tumors.

CONCLUSION: Although the fibroblasts discharge important functions, their gene expression profiles do not represent the breast tissue to the extent that any prognostic decisions could be made.}, } @article {pmid16581652, year = {2006}, author = {Kwaepila, N and Burns, G and Leong, AS}, title = {Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis?.}, journal = {Pathology}, volume = {38}, number = {2}, pages = {125-131}, doi = {10.1080/00313020600559975}, pmid = {16581652}, issn = {0031-3025}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Fatty Acid Transport Proteins/*metabolism ; Female ; Genes, Tumor Suppressor ; Humans ; Neoplasm Proteins/*metabolism ; }, abstract = {AIMS: To examine the immunohistological expression in human breast cancers of human FAT1 (hFAT) protein, a recently described member of the cadherin superfamily, and its correlation with histological type and grade.

METHODS: A total of 326 cases of invasive and in situ breast cancer representing a broad spectrum of histological subtypes were immunostained with affinity-purified rabbit antibodies produced to the cytoplasmic region of hFAT using a standard avidin-biotin system. Staining intensity was arbitrarily graded on a scale of 0 to 3.

RESULTS: All tumours showed diffuse staining for hFAT. Immunoexpression of the protein was generally strong in both lobular (LCIS, n = 2) and ductal in situ carcinoma (DCIS, n = 55). hFAT was also strongly immunoexpressed in all types of invasive carcinoma. Grade 3 DCIS displayed the highest hFAT intensity compared with lower grade tumours, with significant differences between grade 1 and 3 (p = 0.015) and grade 2 and 3 (p = 0.047). With invasive ductal carcinomas (n = 128) the difference was not as clear-cut, as most tumours showed moderate (n = 63) or strong staining (n = 49), although grade 3 IDC revealed significantly decreased immunoexpression compared with grade 1 IDC (p = 0.03).

CONCLUSIONS: The results illustrate that hFAT1 does not display the pattern of expression seen with the E-cadherin-ss-catenin adhesion complex; however, its over-expression and diffuse expression in both in situ and invasive carcinoma strongly suggests a role in carcinogenesis. From the known functions of FAT1 it is suggested that the concurrent loss of classical cadherins from cell-cell junctions accompanied by increased FAT1 expression contributes to loss of duct formation, and increased cell migration and invasion.}, } @article {pmid16569492, year = {2006}, author = {Broekhuizen, LN and Wijsman, JH and Peterse, JL and Rutgers, EJ}, title = {The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {32}, number = {5}, pages = {502-506}, doi = {10.1016/j.ejso.2006.02.006}, pmid = {16569492}, issn = {0748-7983}, mesh = {Adenocarcinoma/pathology/secondary ; Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology ; Carcinoma/pathology/*secondary ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/pathology/*secondary ; Carcinoma, Lobular/pathology/secondary ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Neoplastic Cells, Circulating/pathology ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Survival Rate ; }, abstract = {AIM: To report the incidence and predictive value of positive axillary nodes in ductal carcinoma in situ (DCIS) and T1a carcinoma of the breast.

METHODS: Cases from The Netherlands Cancer Institute were used to determine the incidence of lymph-node metastases. All consecutive patients with primary breast cancer that were treated between 1989 and 1998 and who had undergone axillary dissection were selected. Patients were identified with pure DCIS (n = 71), DCIS with small invasion (n = 12), invasive ductal/lobular carcinoma (IDC/ILC) < or =5 mm (n = 18) or tubular carcinoma < or =10 mm (n = 17). All archived lymph nodes of these patients were re-evaluated using immunohistochemistry (IHC).

RESULTS: In DCIS the incidence increased from 1.4% with routine staining to 11% with IHC. For DCIS with small invasion it was 0 vs 27%, respectively. In IDC/ILC sized 2-5 mm the incidence rose from 6 to 12% and in tubular carcinoma < or =10 mm from 0 to 12%. All but one of the immunohistochemically detected metastases were isolated tumour cells (n = 9) or small (micro)metastases (n = 4). Maximally two nodes per patient were affected. None of the patients with positive lymph nodes died during follow-up (mean 102 months).

CONCLUSIONS: Survival of our patients appeared not to be influenced by the finding of micrometastases in the lymph nodes by IHC. Immunohistochemistry of the sentinel node seems not contributive to further treatment in these patients.}, } @article {pmid16567872, year = {2006}, author = {Satish Rao, BS and Krishnanand, BR and Krishan, A}, title = {Androgen & vitamin D nuclear receptor expression in archival breast tumour samples.}, journal = {The Indian journal of medical research}, volume = {123}, number = {1}, pages = {73-82}, pmid = {16567872}, issn = {0971-5916}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast Neoplasms/*chemistry/pathology ; Cell Nucleus/chemistry ; Female ; Humans ; Middle Aged ; Receptors, Androgen/*analysis ; Receptors, Calcitriol/*analysis ; Regression Analysis ; }, abstract = {BACKGROUND & OBJECTIVE: Breast tumour cells have receptors for androgen and vitamin D and their clinical significance is not completely understood. Therefore, the present study was undertaken to analyze androgen and vitamin D receptor levels in human primary infiltrating ductal breast carcinomas (IDC) and benign breast tumour archival samples and to find out their correlation, if any, with the clinical findings.

METHODS: Paraffin blocks of benign and malignant breast tumours were sectioned, deparaffinized, and nuclei released by pepsin digestion. After antigen retrieval, nuclei were stained with primary antibodies for androgen or vitamin D receptors and secondary fluorescein isothiocyanate (FITC) labeled antibodies and propidium iodide respectively, to quantitative receptor expression and DNA content by flow cytometry.

RESULTS: Androgen receptor positive nuclei ranged from 16-66 per cent in the IDC tumours as compared to 36-67 per cent in the benign tumours. Based on flow cytometric comparison of AR expression in AR positive and negative cell lines established earlier, 24 of 28 tumours from postmenopausal women were AR positive compared to all benign tumours and 32 of 33 tumours from pre-menopausal patients. Vitamin D receptor positive nuclei ranged from 14-89 and 2-75 per cent in IDC and benign tumours, respectively. All pre- or post-menopausal tumours were VDR positive as compared to 10 of 15 benign tumours that were VDR positive. No correlation was seen between nuclear androgen and vitamin D receptor expression of the IDC or benign tumours. There was a positive correlation between per cent of receptor positive nuclei and antigen density as measured by ratio of the mean log fluorescence channel value (MFC). No statistically significant correlation was found between nuclear receptor expression (per cent positive nuclei or antigen density) with that of tumour stage, lymph node status, tumour grade, patient age or menopausal status.

There was no significant correlation between androgen or vitamin D receptor expression and clinical findings. The expression of AR and VDR and the antigen density in the nuclei of the archival breast tumour samples were highly variable because of the tumour heterogeneity. Future studies with fresh biopsy samples of tumour on AR and VDR levels and their up- or down-regulation may be useful while stratifying the patients for hormonal therapy.}, } @article {pmid16552336, year = {2006}, author = {Sanada, Y and Yoshida, K and Ohara, M and Oeda, M and Konishi, K and Tsutani, Y}, title = {Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components.}, journal = {Pancreas}, volume = {32}, number = {2}, pages = {164-170}, doi = {10.1097/01.mpa.0000202947.80117.a0}, pmid = {16552336}, issn = {1536-4828}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/genetics/pathology/physiopathology/surgery ; Disease Progression ; Female ; Gastric Mucosa/*pathology ; HMGB Proteins/*genetics ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mucin 5AC ; Mucins ; Neoplasm Invasiveness ; Pancreatic Ducts/pathology ; Pancreatic Neoplasms/genetics/*pathology/physiopathology/surgery ; Retrospective Studies ; SOXB1 Transcription Factors ; Transcription Factors/*genetics ; }, abstract = {OBJECTIVES: The purpose of this study was to perform histopathologic and immunohistochemical analyses of gastric transcription factor SOX2 and gastric mucin MUC5AC to better understand the stepwise progression of pancreatic carcinoma.

METHODS: Twenty-eight representative sections from 14 surgically resected pancreatic carcinomas were assessed microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma (IDC) were determined. The expression of SOX2 and MUC5AC in PanIN and IDC was examined immunohistochemically.

RESULTS: One hundred thirty-eight PanINs were identified. In 4 of the 14 cases, gradual transition from PanIN-1A to PanIN-3 was observed in a single duct, suggesting stepwise progression. The expression of MUC5AC increased with the progression of lesions from PanIN-1A to PanIN-3. SOX2 was expressed in only 6 of 107 early PanINs (5.8%). Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis. In addition, SOX2 was frequently and strongly expressed in poorly differentiated (57.1%) and neurally invasive (63.6%) components.

CONCLUSIONS: The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.}, } @article {pmid16552071, year = {2006}, author = {Dionne, SO and Podany, AB and Ruiz, YW and Ampel, NM and Galgiani, JN and Lake, DF}, title = {Spherules derived from Coccidioides posadasii promote human dendritic cell maturation and activation.}, journal = {Infection and immunity}, volume = {74}, number = {4}, pages = {2415-2422}, pmid = {16552071}, issn = {0019-9567}, support = {P01 AI061310/AI/NIAID NIH HHS/United States ; IP01AI061310-01/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Adhesion/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coccidioides/cytology/*immunology/metabolism ; Dendritic Cells/*cytology/*immunology/metabolism ; Dose-Response Relationship, Immunologic ; Fungal Vaccines/immunology ; Humans ; Leukocytes, Mononuclear/immunology ; }, abstract = {Previous studies have shown that dendritic cells (DC) pulsed with T27K, an antigenic preparation derived from spherules (of Coccidioides posadasii), activate peripheral blood mononuclear cells (PBMC) from nonimmune subjects as well as from patients with disseminated coccidioidomycosis. In this study, we have assessed the interaction between human DC and C. posadasii spherules in order to better understand the initial response between Coccidioides and the human host. Whole autoclaved spherules induced lymphocyte transformation in PBMC obtained from immune but not from nonimmune donors. Immature DC (iDC) bound fluorescein isothiocyanate-labeled spherules in a time- and temperature-dependent manner. This binding was blocked by the addition of mannan, suggesting mannose receptor involvement in the DC-Coccidioides interaction. Binding was subsequently associated with ingestion and intracellular processing of spherules. Coculturing of spherules with iDC was associated with the development of mature DC that were morphologically, phenotypically, and functionally similar to those induced by tumor necrosis factor alpha and prostaglandin E2. Finally, spherules incubated with iDC induced activation of PBMC from nonimmune donors. These data indicate that human DC are capable of binding, internalizing, and presenting antigens from Coccidioides spherules and suggest that DC may play a critical early role in the formation of a cellular immune response in human coccidioidomycosis.}, } @article {pmid16540006, year = {2006}, author = {Ruibal, A and Garrido-Pumar, M and Arias, JI}, title = {[Expression of epidermal growth factor receptor (EGFR) in hormone-independent breast cancers].}, journal = {Revista espanola de medicina nuclear}, volume = {25}, number = {1}, pages = {15-19}, doi = {10.1157/13083345}, pmid = {16540006}, issn = {0212-6982}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Cathepsin D/analysis ; Cell Division ; ErbB Receptors/*analysis ; Female ; Humans ; Hyaluronic Acid/analysis ; Membrane Proteins/analysis ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins/*analysis ; Presenilin-2 ; Radioligand Assay ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tissue Plasminogen Activator/analysis ; }, abstract = {OBJECTIVE: To determine the expression of epidermal growth factor receptor (EGFR) in ER-negative and Pg-R negative infiltrating ductal carcinomas of the breast (IDC) and to analyze the possible relationship between the EGFR positivity and some clinico-biological parameters of tumors.

MATERIAL AND METHODS: EGFR was measured by a single point radioligand assay in the cell surfaces of 115 ER-negative and Pg-R-negative (< 10 fmol/mg prot.) IDC. We measured also the cytosolic concentrations of pS2, cathepsin D, tissue-type plasminogen activator (t-PA) and hyaluronic acid (AH), as well as the levels of AH in cell surfaces. Tumor size, axillary involvement, distant metastasis, histological grading, ploidy and S-phase (SP) were taken account.

RESULTS: Using as cut-off for EGFR a value of 5 fmol/mg prot., we can observed that IDCs -EGFR + had greater global values of S-phase (p: 0.005) and were more frequently metastastatic (p: 0.004), SP > 7 % (p < 0.001) and SP > 14 % (p: 0.077); likewise, they were lower frequently pS2-positive (p < 0.01) and t-PA-positive (p < 0.01). During the follow up time (median 85 months), the number of recurrences was higher in EGFR-positive than in EGFR- negative tumors (14/41 frente a 1/29; p: 0.002), but there was not differences in the number of deaths by the tumor.

CONCLUSIONS: 1) The EGFR-positivity in ER-negative and PgR-negative IDCs is associated with distant metastasis, greater cellular proliferation (SP), lower positivity for pS2 and t-PA and greater number of recurrences. 2) Using 10 fmol/mg prot. as cut-off, we observed the same findings, except the change in cellular proliferation. 3) Our findings support the possible use of EGFR as a prognostic parameter in those breast carcinomas.}, } @article {pmid16538528, year = {2006}, author = {Tsutsui, S and Inoue, H and Yasuda, K and Suzuki, K and Takeuchi, H and Nishizaki, T and Higashi, H and Era, S and Mori, M}, title = {Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density.}, journal = {Breast cancer research and treatment}, volume = {98}, number = {3}, pages = {261-266}, doi = {10.1007/s10549-005-9157-9}, pmid = {16538528}, issn = {0167-6806}, mesh = {Adult ; Aged ; Aged, 80 and over ; Angiopoietin-2/*biosynthesis ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Disease-Free Survival ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; *Microcirculation ; Middle Aged ; Multivariate Analysis ; Treatment Outcome ; Vascular Endothelial Growth Factor A/*biosynthesis/metabolism ; }, abstract = {Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.}, } @article {pmid16538049, year = {2006}, author = {Carter, MR and Hornick, JL and Lester, S and Fletcher, CD}, title = {Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases.}, journal = {The American journal of surgical pathology}, volume = {30}, number = {3}, pages = {300-309}, doi = {10.1097/01.pas.0000184809.27735.a1}, pmid = {16538049}, issn = {0147-5185}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*metabolism/*pathology/therapy ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Metastasis/pathology ; Sarcoma/*metabolism/*pathology/therapy ; Treatment Outcome ; }, abstract = {Spindle cell (sarcomatoid) carcinoma of the breast is a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma. Because the term "metaplastic carcinoma" comprises a heterogeneous group of tumors, it has been difficult to reliably predict biologic potential or to determine optimal therapy. To better characterize the spindle cell subset of metaplastic breast carcinomas, we reviewed 29 cases. All patients were adult females ranging from 40 to 96 years of age (median, 68 years). Tumor size ranged from 1.5 to 15 cm (median, 4 cm). Treatment was by excision and/or mastectomy with axillary node evaluation in most cases, often combined with postoperative radiation and/or chemotherapy. All cases were clinically of breast origin, showed >or=80% spindled/sarcomatoid morphology, and demonstrated keratin positivity and/or close association with ductal carcinoma in situ. Immunohistochemical studies showed evidence suggesting myoepithelial differentiation as exhibited by immunoreactivity for smooth muscle actin, cytokeratin 14, and p63 in a subset of cases (39%). Twenty-seven cases exhibited pure spindled or sarcomatoid morphology of variable appearance and nuclear grade, whereas 2 contained high-grade invasive ductal carcinoma comprising
METHODS: Eighty cases showing IMPC or IMPC-like pattern were selected from our surgical files of 1,240 cases of IDC. We examined the expression of MUC1, D2-40 and CD34 by immunohistochemistry.

RESULTS: Eighty cases were classified into 9 cases (0.7%) of pure-IMPC, 31 cases (2.5%) of mixed-IMPC, and 40 cases of pseudo-IMPC, according to the expression pattern of MUC1. In pure-IMPC cases, MUC1 expression was found at the reversed apical membrane of neoplastic cell clusters, while in pseudo-IMPC, MUC1 expression was present in the whole cytoplasmic membrane and/or cytoplasm. There were no significant differences among the three groups in patient age, tumor size and nuclear grade of neoplastic cells. However, lymphatic invasion and lymph node metastasis in the pure-IMPC or mixed-IMPC cases were higher than those in pseudo-IMPC cases with statistically significant values. Pure-IMPC has a higher recurrence rate and lower overall survival compared to pseudo-IMPC [P = 0.0165(DFS) P = 0.025(OS)].

CONCLUSIONS: This study demonstrated that immunohistochemistry of MUC1 is useful for the diagnosis of IMPC. The pure-IMPC cases had higher incidences of lymphatic invasion and lymph node metastasis, and also showed a poorer prognosis.}, } @article {pmid16509555, year = {2006}, author = {Quilon, JM and Gaskin, TA and Ludwig, AS and Alley, C}, title = {Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast.}, journal = {Southern medical journal}, volume = {99}, number = {2}, pages = {164-167}, doi = {10.1097/01.smj.0000198640.58397.c5}, pmid = {16509555}, issn = {0038-4348}, mesh = {Biopsy ; Bone Marrow/pathology ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone/*pathology/surgery ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasms, Multiple Primary ; }, abstract = {Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.}, } @article {pmid16507410, year = {2005}, author = {Lui, EL and Loo, WT and Zhu, L and Cheung, MN and Chow, LW}, title = {DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {59 Suppl 2}, number = {}, pages = {S363-5}, doi = {10.1016/s0753-3322(05)80079-4}, pmid = {16507410}, issn = {0753-3322}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; *DNA Methylation ; DNA, Neoplasm/biosynthesis/genetics ; Female ; Humans ; Lymphatic Metastasis/pathology ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Inhibitor of Metalloproteinase-3/*genetics ; }, abstract = {BACKGROUND: Neoplastic cells often display aberrant methylation and silencing of multiple genes, including tumor suppressor genes (TSGs) that regulate critical processes such as cell cycle control, DNA repair and angiogenesis. Tissue inhibitor of metalloproteinase-3 (TIMP3) is an extracellular matrix-bound protein which regulates matrix composition and affects tumor growth, invasion and angiogenesis. It mediates vascular endothelial growth factor (VEGF) by blocking the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling. This study focused on the hypermethylation status of the TIMP3 gene with clinical parameters in invasive breast ductal carcinoma (IDC) samples.

MATERIALS AND METHODS: DNA extraction and methylation specific PCR (MSP) was performed on 173 patients with invasive breast carcinoma. Both specific methylated and unmethylated primers for each gene were used for PCR and the products were visualized on agarose gel. The methylation status of TIMP3 was then compared with corresponding patients' clinicopathologic characteristics.

RESULTS: Methylation frequencies of TIMP3 in the breast cancer samples were 20.81 %. Among the hypermethylated cancers, 50% were tumor grade II-III, 44.44% were positive in lymph node involvement (LN), 36.11% were positive in lymphovascular permeation (LVP); 44.44%, 22.22% and 47.22% for the overexpressions in estrogen receptor (ER), progesterone receptor(PR) and c-erbB2, respectively.

CONCLUSION: The result demonstrated that hypermethylation of TIMP3 in IDC might be associated with high tumor grading and lymph nodes metastasis, and overexpression of ER, PR and c-erbB2, respectively.}, } @article {pmid16507397, year = {2005}, author = {Chow, LW and Loo, WT and Wai, CC and Lui, EL and Zhu, L and Toi, M}, title = {Study of COX-2, Ki67, and p53 expression to predict effectiveness of 5-flurouracil, epirubicin and cyclophosphamide with celecoxib treatment in breast cancer patients.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {59 Suppl 2}, number = {}, pages = {S298-301}, doi = {10.1016/s0753-3322(05)80050-2}, pmid = {16507397}, issn = {0753-3322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/administration & dosage ; Antimetabolites, Antineoplastic/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/enzymology ; Celecoxib ; Cell Proliferation/drug effects ; Cyclooxygenase 2/*biosynthesis ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Cyclophosphamide/administration & dosage ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Middle Aged ; Pyrazoles/*therapeutic use ; Sulfonamides/*therapeutic use ; }, abstract = {BACKGROUND: Cyclooxygenase-2 (COX-2) affects cell proliferation, apoptosis, and metastasis of breast cancer, and may also be involved in tumor angiogenesis through vascular endothelial growth factor. Ki67 and p53 are common markers of proliferation and apoptosis in tumor cells. This study investigated the change in expression of COX-2, Ki67, and p53 in solid tumors after the administration of chemotherapeutic drugs.

MATERIALS AND METHODS: Fifty patients were eligible to be treated with preoperative 5-fluorouracil, epirubicin, and cyclophosphamide, with celecoxib (FECC). Tumor tissue samples from 10 patients who, diagnosed with invasive ductal carcinoma, completed chemotherapy were examined immunohistochemically for COX-2, Ki67, and p53.

RESULTS: From the 60% of patients who expressed COX-2 and 90% who expressed Ki67 and p53 before treatment, 90% of patients revealed a lower intensity staining for each marker after FECC treatment. However, changes in expression of the three markers did not significantly correlate with tumor size, grade, axillary lymph node status. Immunostained slides clearly showed that the diaminobenzidine intensity was markedly reduced after the three-cycle FECC treatment, which implied the combined regimens be effective to the cancer patients.

CONCLUSIONS: This study demonstrates a novel relationship between COX-2, Ki67, and p53 expression of human breast invasive ductal carcinomas. This functional relationship provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer.}, } @article {pmid16498929, year = {2006}, author = {Sardanelli, F and Lupo, P and Esseridou, A and Fausto, A and Quarenghi, M}, title = {Dynamic breast magnetic resonance imaging without complications in a patient with dual-chamber demand pacemaker.}, journal = {Acta radiologica (Stockholm, Sweden : 1987)}, volume = {47}, number = {1}, pages = {24-27}, doi = {10.1080/02841850500409542}, pmid = {16498929}, issn = {0284-1851}, mesh = {Aged ; Breast/*pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Female ; Humans ; Magnetic Resonance Imaging/*adverse effects/methods ; Mammography/methods ; *Pacemaker, Artificial ; }, abstract = {Mammography and ultrasound indicated a cancer of the right breast in a 77-year-old woman with a dual-chamber demand pacemaker. The patient was not pacemaker-dependent. She underwent breast 1.5T magnetic resonance imaging (MRI) (dynamic gradient echo sequence with Gd-DOTA 0.1 mmol/kg). Before the patient entered the MR room, the configuration of the device was changed (the response to magnet was switched from asynchronous to off and the rate-responsive algorithm was disabled). No relevant modifications of heart rhythm or rate were observed during the MR examination. No symptom was reported. Immediately after the examination, the pacemaker interrogation showed neither program changes nor alert warnings. MRI detected a bifocal cancer in the right breast which allowed tailored breast-conserving treatment to be initiated. Histopathology confirmed a bifocal invasive ductal carcinoma.}, } @article {pmid16493140, year = {2006}, author = {Llinás, M and Bozdech, Z and Wong, ED and Adai, AT and DeRisi, JL}, title = {Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains.}, journal = {Nucleic acids research}, volume = {34}, number = {4}, pages = {1166-1173}, pmid = {16493140}, issn = {1362-4962}, support = {U01 AI053862/AI/NIAID NIH HHS/United States ; AI53862/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigenic Variation ; Antigens, Protozoan/genetics ; Drug Resistance ; Erythrocytes/parasitology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Protozoan ; Phenotype ; Plasmodium falciparum/drug effects/*genetics/growth & development ; RNA, Messenger/metabolism ; RNA, Protozoan/*metabolism ; Species Specificity ; Transcription, Genetic ; }, abstract = {Gene expression patterns have been demonstrated to be highly variable between similar cell types, for example lab strains and wild strains of Saccharomyces cerevisiae cultured under identical growth conditions exhibit a wide range of expression differences. We have used a genome-wide approach to characterize transcriptional differences between strains of Plasmodium falciparum by characterizing the transcriptome of the 48 h intraerythrocytic developmental cycle (IDC) for two strains, 3D7 and Dd2 and compared these results to our prior work using the HB3 strain. These three strains originate from geographically diverse locations and possess distinct drug sensitivity phenotypes. Our goal was to identify transcriptional differences related to phenotypic properties of these strains including immune evasion and drug sensitivity. We find that the highly streamlined transcriptome is remarkably well conserved among all three strains, and differences in gene expression occur mainly in genes coding for surface antigens involved in parasite-host interactions. Our analysis also detects several transcripts that are unique to individual strains as well as identifying large chromosomal deletions and highly polymorphic regions across strains. The majority of these genes are uncharacterized and have no homology to other species. These tractable transcriptional differences provide important phenotypes for these otherwise highly related strains of Plasmodium.}, } @article {pmid16487965, year = {2006}, author = {Fragoso, JM and Rodríguez-Pérez, JM and González, J and Cruz, D and Pérez-Méndez, O and de Jesus García, J and de la Peña, A and Arce, M and Reyes, PA and Vargas-Alarcón, G}, title = {Beta1-adrenergic receptor gene polymorphisms in Mexican patients with idiopathic dilated cardiomyopathy.}, journal = {Experimental and molecular pathology}, volume = {80}, number = {3}, pages = {279-282}, doi = {10.1016/j.yexmp.2005.12.005}, pmid = {16487965}, issn = {0014-4800}, mesh = {Cardiomyopathy, Dilated/*genetics ; Gene Frequency ; *Genetic Predisposition to Disease ; Humans ; Mexico ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Adrenergic, beta-1/*genetics ; }, abstract = {The objective of the study was to evaluate the role of beta1-adrenergic receptor gene polymorphisms (Ser49Gly and Arg389Gly) as susceptibility markers for idiopathic dilated cardiomyopathy (IDC) in Mexican patients. The polymorphisms were analyzed in 47 patients with IDC and 93 ethnically matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The Ser49Gly allele and genotype frequencies were similar in patients and healthy controls. On the other hand, the analysis of the Arg389Gly polymorphism showed an increased frequencies of the *Gly allele (pC = 0.022, OR = 2.16) and *Arg/*Gly genotype (pC = 0.027, OR = 2.70) in the group of IDC patients when compared to healthy controls. The data suggest that Arg389Gly polymorphism could be involved in the genetic susceptibility to develop IDC in Mexicans.}, } @article {pmid16472480, year = {2006}, author = {Otero-López, MJ and Alonso-Hernández, P and Maderuelo-Fernández, JA and Garrido-Corro, B and Domínguez-Gil, A and Sánchez-Rodríguez, A}, title = {[Preventable adverse drug events in hospitalized patients].}, journal = {Medicina clinica}, volume = {126}, number = {3}, pages = {81-87}, doi = {10.1157/13083875}, pmid = {16472480}, issn = {0025-7753}, mesh = {*Drug-Related Side Effects and Adverse Reactions ; Hospitalization/*statistics & numerical data ; Humans ; *Medication Errors/statistics & numerical data ; }, abstract = {BACKGROUND AND OBJECTIVE: To determine the incidence of adverse drug events (ADE) in hospitalized patients, identify those that were potentially preventable, and asses the drug classes involved, the clinical symptoms and the type of medication errors that led to the preventable ADE.

PATIENTS AND METHOD: An observational study of ADE prevalence in hospitalized patients in internal medicine, pneumology, gastroenterology, nephrology and neurology wards, over a six-month period, at a tertiary university hospital. ADE were prospectively detected through physician and nurses reporting fostered by daily visits of a clinical research and retrospectively through review of medical records using event codes as defined by the IDC-9-CM system.

RESULTS: In a total of 2,643 hospitalized patients, 191 (7.2%) ADE were detected. Of these, 38 cases (19.9%) were classified as preventable, of which 21.1% were mild; 60.5% moderate and 18.4% serious or life-threatening. Preventable ADE were frequently associated with anti-infective drugs (22.9%), diuretics (18.8%) and digoxin (16.7%). Inadequate therapy monitoring (28.3%), excessive dosage (21.7%), selection of an inappropriate drug according to patient characteristics and/or to diagnosis (15.0%), lack of prescription of a necessary drug (15.0%) and drug-drug interactions (11.7%) were the most common identified type of errors leading to preventable ADE.

CONCLUSIONS: 1.4% of hospitalized patients in medical wards experienced potentially preventable ADE. Healthcare professionals and administrators must be made aware of the scope of this problem so that they will implement effective safety practices directed to reduce the incidence of medication errors, particularly prescription and monitoring errors.}, } @article {pmid16471119, year = {2005}, author = {Sampatanukul, P and Chaiwun, B and Wongwaisayawan, S and Suwanagool, P and Vinyuvat, S and Karalak, A and Praditphol, N and Paueksakon, P and Ruangvejvorachai, P and Field, AS and Wannakrairot, P}, title = {A two-phase study model for the standardization of HER2 immunohistochemical assay on invasive ductal carcinoma of the breast.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {88}, number = {11}, pages = {1680-1688}, pmid = {16471119}, issn = {0125-2208}, mesh = {Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Clinical Protocols ; Coloring Agents ; Female ; Genes, erbB-2/*immunology ; Humans ; Immunohistochemistry/methods/*standards ; Models, Theoretical ; Pathology, Clinical/methods/*standards ; Receptor, ErbB-2/*immunology ; Thailand ; }, abstract = {OBJECTIVES: To develop and verify a standardized protocol for HER2 immunohistochemical assays on invasive ductal carcinoma of the breast in Thailand.

MATERIAL AND METHOD: A two-phase study approach was employed. In the Phase One, after verifying the proposed protocol that adopted the HercepTest procedure using readily available primary antibodies, CB11 and A0485, Lab 1 performed the HER2 immunohistochemical staining for 137 cases of invasive ductal carcinoma twice with two types of the antibody. Nine pathologists from 8 centers independently examined and scored all the 2 x 137 stained slides that were blinded for antibody type. Interobserver reliability was calculated using pair-wise kappa. Following discussion of the results, the Phase Two study was planned. Lab 2 and Lab 3 independently performed the HER2 staining according to the protocol for 60 invasive breast carcinoma cases. The same group of pathologists scored 2 x 60 stained slides that were masked for laboratories. Interobserver reliability and interlaboratory agreement from each pathologist were calculated using kappa statistics. Three interpreted categories--namely negative, equivocal and positive tests were used in the analyses.

RESULTS: Phase One study showed interobserver agreement between pairs varied from kappa 0.75 (95%CI, 0.68-0.82) to 0.06 (95%CI, 0-0.14) while Phase Two study obtained pair-wise kappa scores ranged from 0.84 (95%CI, 0. 80-0.89) to 0. 65 (95%CI, 0.59-0.71). Interlaboratory kappa for each pathologist was 0.67 (95%CI, 0.61-0.73).

CONCLUSION: The standardization of HER2 immunohistochemical assay was achieved through this two-phase study model. It had added benefits of improving pathologists' expertise and verifying the HER2 testing protocol to be used in Thailand.}, } @article {pmid16469432, year = {2006}, author = {Jang, KS and Han, HX and Paik, SS and Brown, PH and Kong, G}, title = {Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intratumoral microvessel density in ER-negative/node-positive breast cancer.}, journal = {Cancer letters}, volume = {244}, number = {2}, pages = {203-210}, doi = {10.1016/j.canlet.2005.12.016}, pmid = {16469432}, issn = {0304-3835}, mesh = {Adenocarcinoma/blood supply/metabolism/pathology ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Inhibitor of Differentiation Protein 1/*metabolism ; Lymph Nodes/*pathology ; Microcirculation ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Neoplasms, Ductal, Lobular, and Medullary/blood supply/metabolism/pathology ; Neovascularization, Pathologic/*metabolism ; Prognosis ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {The aim of this study is to investigate the possible role of inhibitor of DNA binding (Id-1) overexpression in human breast cancer. We examined Id-1 expression by immunohistochemistry in 263 human breast cancers, 15 in situ lesions and 248 invasive cancers to investigate the relationship between its expression and various clinicopathological factors. Id-1 expression was significantly higher in invasive ductal carcinoma than in in situ ductal carcinoma or other invasive cancer subtypes (P=0.029 and 0.006, respectively). We also examined the association between Id-1 expression and tumor angiogenesis by measuring microvessel densities (MVD). Regarding the endothelial cells of microvessels showed negative or very weak Id-1 expression, Id-1 overexpression was found to be significantly related to MVD (P=0.014). Furthermore, Id-1 overexpression was found to be significantly associated with higher MVD in the ER-negative and node-involved subgroups of breast cancer (P=0.040 and 0.046, respectively). These data indicate that Id-1 overexpression is significantly associated with tumor angiogenesis, especially in the ER-negative and node-positive subtypes of invasive breast cancer. Thus, Id-1 presents a possible therapeutic antitumor target molecule in ER-negative and node-positive breast cancer.}, } @article {pmid16457686, year = {2005}, author = {Morikawa, A and Williams, TY and Dirix, L and Colpaert, C and Goodman, M and Lyles, RH and Zhong, D and Zhou, W}, title = {Allelic imbalances of chromosomes 8p and 18q and their roles in distant relapse of early stage, node-negative breast cancer.}, journal = {Breast cancer research : BCR}, volume = {7}, number = {6}, pages = {R1051-7}, pmid = {16457686}, issn = {1465-542X}, mesh = {Adult ; Aged ; *Allelic Imbalance ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Case-Control Studies ; Chromosomes, Human, Pair 18/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis/genetics ; Neoplasm Staging ; }, abstract = {INTRODUCTION: Identification of breast cancer patients at risk for postoperative distant relapse is an important clinical issue. Existing pathological markers can predict disease recurrence only to a certain extent, and there is a need for more accurate predictors.

METHODS: Using 'counting alleles', a novel experimental method, we determined allelic status of chromosomes 8p and 18q in a case-control study with 65 early stage, node negative, invasive ductal carcinomas (IDCs). The association between allelic imbalance (AI) of both chromosomal markers and distant relapses was examined.

RESULTS: Eighty percent of tumors contained 8pAI and sixty-eight percent of tumors contained 18qAI. However, none of the tumor samples retained both chromosome 8p and 18q alleles. More importantly, tumors with 8pAI but not 18qAI were more likely to have distant relapse compared to tumors with 18qAI but not 8pAI.

CONCLUSION: Our finding suggests that differential allelic loss of chromosomes 8p and 18q may represent subtypes of early stage IDC with different tumor progression behaviors.}, } @article {pmid16455138, year = {2006}, author = {Metharom, P and Velten, FW and Goerdt, S}, title = {Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by tumour-conditioned media retain the capacity to mature and induce TH1 T-cell proliferation.}, journal = {Molecular immunology}, volume = {43}, number = {13}, pages = {2070-2082}, doi = {10.1016/j.molimm.2005.12.008}, pmid = {16455138}, issn = {0161-5890}, mesh = {Antigen-Presenting Cells/cytology/*immunology ; Antigens, CD/*immunology ; CD4 Antigens/*immunology ; Cell Differentiation/drug effects/immunology ; Cell Line, Tumor ; *Cell Proliferation/drug effects ; Culture Media, Conditioned/pharmacology ; Cytokines/immunology ; GPI-Linked Proteins ; Humans ; Lipopolysaccharide Receptors/*immunology ; Neoplasms/immunology ; Receptors, IgG/*immunology ; Th1 Cells/*immunology ; }, abstract = {The tumour microenvironment down-modulates antigen-presentation by dendritic cells (DC), presumably due to inhibition of DC maturation. Here, we sought to examine (1) whether monocyte-derived cells cultivated with tumour-conditioned media under conditions that are conducive to DC generation (APCTCM) resemble immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are functionally defective. Four tumour cell lines expressing different cytokines were used to mimic different tumour microenvironments. As compared to iDC, DCims or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and CD4. These markers and a high phagocytic capacity were unique features of these cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR and CD25 were up-regulated to levels considerably higher than in DCIL10 and comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated. Activated APCTCM induced 50-60% of the proliferative response of DCims in the allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC elicited approximately 10%). Activated APCTCM induced secretion of almost equal amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1 differentiation. When mature DCims were exposed to TCM, their immunostimulatory function was not significantly altered. However, when TCM were added to the co-cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the TCM. In summary, APCTCM display special features but can mature into DCims-like cells.}, } @article {pmid16442946, year = {2006}, author = {Dillon, MF and Hill, AD and Fleming, FJ and O'Doherty, A and Quinn, CM and McDermott, EW and O'Higgins, N}, title = {Identifying patients at risk of compromised margins following breast conservation for lobular carcinoma.}, journal = {American journal of surgery}, volume = {191}, number = {2}, pages = {201-205}, doi = {10.1016/j.amjsurg.2005.03.041}, pmid = {16442946}, issn = {0002-9610}, mesh = {Breast Neoplasms/diagnosis/pathology/*surgery ; Carcinoma, Ductal/pathology/surgery ; Carcinoma, Lobular/diagnosis/pathology/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness/*diagnosis ; }, abstract = {BACKGROUND: The association of invasive lobular carcinoma with high rates of compromised margins in breast conservation makes choice of operation for these patients difficult. We sought to identify patients at risk of compromised margins following breast conservation surgery.

METHODS: We reviewed all patients with invasive lobular and invasive ductal carcinoma over a 5-year period (1999-2004). The imaging, pathology and surgical details of patients with invasive lobular carcinoma undergoing breast conservation were analyzed.

RESULTS: A total of 991 patients with invasive ductal carcinoma and 150 patients with invasive lobular carcinoma were identified. Lobular carcinomas had a compromised margin rate of 49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal carcinomas (P < .0001). Mammographic size (P = .017), pathological size (P = .01), age (P = .03), multifocality (P < .0001), and lymphovascular invasion (P = .015) were significantly associated with compromised margins.

CONCLUSION: Invasive lobular carcinoma has a 49% rate of compromised margins following breast conservation. Mammographic size greater than 1.5 cm and young age were preoperative factors predictive of compromised margins.}, } @article {pmid16442403, year = {2006}, author = {Fauchier, L and Poret, P and Robin, I and de Labriolle, A and Giraudeau, C and Cosnay, P and Babuty, D}, title = {Different criteria of cardiac resynchronization therapy and their prognostic value for worsening heart failure or major arrhythmic events in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {97}, number = {3}, pages = {393-399}, doi = {10.1016/j.amjcard.2005.08.059}, pmid = {16442403}, issn = {0002-9149}, mesh = {Adult ; Arrhythmias, Cardiac/*etiology ; Cardiomyopathy, Dilated/complications/*therapy ; Clinical Trials as Topic ; Defibrillators, Implantable ; Disease Progression ; Electric Countershock/*adverse effects/instrumentation ; Female ; Heart Failure/*etiology ; Humans ; Male ; Middle Aged ; *Patient Selection ; Prognosis ; }, abstract = {There are still controversies about pertinent criteria for cardiac resynchronization therapy (CRT) and prophylactic indications for biventricular cardioverter-defibrillators, particularly in idiopathic dilated cardiomyopathy (IDC). This study compared several criteria for resynchronization therapy in IDC among those of several completed trials. In 201 patients with IDC, the relative risk for (1) death from heart failure (HF) or heart transplantation and (2) sudden death or sustained ventricular tachyarrhythmia were calculated separately according to the inclusion criteria of the Multisite Stimulation in Cardiomyopathy (MUSTIC), InSync, Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Pacing Therapies for Congestive Heart Failure (PATH-CHF), Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), and CONTAK studies. The percentage of patients meeting the criteria ranged from 6% for those of MUSTIC to 23% for those of CONTAK. In a follow-up of 51 +/- 42 months, 28 patients died (15 from progressive HF, 13 from sudden death), 20 underwent heart transplantation, and 12 had sustained ventricular tachyarrhythmia. Relative risks of worsening HF ranged from 3.14 (95% confidence interval [CI] 1.41 to 6.99, p = 0.005) for the MIRACLE criteria to 4.63 (95% CI 1.76 to 12.2, p = 0.0019) for the MUSTIC criteria. Only the CONTAK criteria were significantly associated with a risk for major arrhythmic events (2.65, 95% CI 1.19 to 5.95, p = 0.018). Arrhythmic events constituted 16% of all cardiac events for the MUSTIC patients, 11% for InSync patients, 31% for PATH-CHF patients, 36% for MIRACLE patients, 38% for COMPANION patients, and 42% for CONTAK patients. In conclusion, in IDC, the less restrictive criteria for CRT were associated with the greatest risk for arrhythmic events. In contrast, patients with the MUSTIC criteria for CRT mainly had a risk for worsening HF and may not benefit from biventricular cardioverter-defibrillators.}, } @article {pmid16434695, year = {2006}, author = {Chabot, V and Reverdiau, P and Iochmann, S and Rico, A and Sénécal, D and Goupille, C and Sizaret, PY and Sensebé, L}, title = {CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9.}, journal = {Journal of leukocyte biology}, volume = {79}, number = {4}, pages = {767-778}, doi = {10.1189/jlb.0804464}, pmid = {16434695}, issn = {0741-5400}, mesh = {Antibodies/pharmacology ; Basement Membrane/immunology/*metabolism ; Cell Membrane/drug effects/immunology ; Cell Movement/drug effects/*immunology ; Chemokine CCL5 ; Chemokines, CC/antagonists & inhibitors/immunology/*pharmacology ; Collagen/immunology ; Dendritic Cells/drug effects/metabolism/*physiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Humans ; In Vitro Techniques ; Laminin/immunology ; Matrix Metalloproteinase 9/drug effects/*metabolism ; Monocytes/drug effects/immunology ; Proteoglycans/immunology ; RNA, Messenger/biosynthesis/drug effects ; Reference Values ; Time Factors ; Tissue Inhibitor of Metalloproteinases/pharmacology ; }, abstract = {The proinflammatory chemokine CC chemokine ligand 5 (CCL5) is a potent chemoattractant of immature dendritic cells (iDCs). It remains to be elucidated whether CCL5 may also enhance iDC migration through the basement membrane by affecting matrix metalloproteinase (MMP)-9 secretion. In this study, iDCs were differentiated in vitro from human monocytes of healthy donors. Zymographic analysis of cellular membranes of nontreated iDCs revealed a basal secretion of the pro- and active MMP-9, whereas only pro-MMP-9 was detected in conditioned media. Increasing concentrations of CCL5 significantly enhanced MMP-9 secretion by iDCs, peaking at 100 ng/ml, which optimally increased iDC migration through a reconstituted basement membrane (Matrigel) in vitro. The CCL5-enhanced secretion of MMP-9 occurred early (2 h) and was maintained at least for 10 h. A significant increase in MMP-9 mRNA synthesis was detected by reverse transcriptase-polymerase chain reaction, only at 6 h of CCL5 treatment, which suggests that the early effect of CCL5 (0-4 h) on MMP-9 secretion was independent of mRNA synthesis, whereas the more delayed effect (6-10 h) could be mediated through an increase in MMP-9 gene expression. In a Matrigel migration assay, the CCL5-enhanced iDC migration was reduced significantly by specific inhibitors of MMP-9, such as tissue inhibitor of metalloproteinase-1 or an anti-MMP-9 antibody, which indicates that iDC migration through the basement membrane depends on MMP-9. These results suggest that under inflammatory conditions, the chemokine CCL5 may enhance iDC migration through the basement membrane by rapidly increasing their MMP-9 secretion.}, } @article {pmid16428471, year = {2006}, author = {Stange, DE and Radlwimmer, B and Schubert, F and Traub, F and Pich, A and Toedt, G and Mendrzyk, F and Lehmann, U and Eils, R and Kreipe, H and Lichter, P}, title = {High-resolution genomic profiling reveals association of chromosomal aberrations on 1q and 16p with histologic and genetic subgroups of invasive breast cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {12}, number = {2}, pages = {345-352}, doi = {10.1158/1078-0432.CCR-05-1633}, pmid = {16428471}, issn = {1078-0432}, mesh = {Biomarkers, Tumor/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/genetics/metabolism/pathology ; *Chromosome Aberrations ; Chromosomes, Artificial, Bacterial ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; Cluster Analysis ; DNA, Neoplasm ; *Genome, Human ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness/pathology ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; }, abstract = {PURPOSE: Invasive ductal carcinoma and invasive lobular carcinoma (ILC) represent the major histologic subtypes of invasive breast cancer. They differ with regard to presentation, metastatic spread, and epidemiologic features. To elucidate the genetic basis of these differences, we analyzed copy number imbalances that differentiate the histologic subtypes.

EXPERIMENTAL DESIGN: High-resolution genomic profiling of 40 invasive breast cancers using matrix-comparative genomic hybridization with an average resolution of 0.5 Mb was conducted on bacterial artificial chromosome microarrays. The data were subjected to classification and unsupervised hierarchical cluster analyses. Expression of candidate genes was analyzed in tumor samples.

RESULTS: The highest discriminating power was achieved when combining the aberration patterns of chromosome arms 1q and 16p, which were significantly more often gained in ILC. These regions were further narrowed down to subregions 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. Located within the candidate gains on 1q are two genes, FMO2 and PTGS2, known to be overexpressed in ILC relative to invasive ductal carcinoma. Assessment of four candidate genes on 16p11.2 by real-time quantitative PCR revealed significant overexpression of FUS and ITGAX in ILC with 16p copy number gain. Unsupervised hierarchical cluster analysis identified three molecular subgroups that are characterized by different aberration patterns, in particular concerning gain of MYC (8q24) and the identified candidate regions on 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. These genetic subgroups differed with regard to histology, tumor grading, frequency of alterations, and estrogen receptor expression.

CONCLUSIONS: Molecular profiling using bacterial artificial chromosome arrays identified DNA copy number imbalances on 1q and 16p as significant classifiers of histologic and molecular subgroups.}, } @article {pmid16427184, year = {2006}, author = {Miki, Y and Clyne, CD and Suzuki, T and Moriya, T and Shibuya, R and Nakamura, Y and Ishida, T and Yabuki, N and Kitada, K and Hayashi, S and Sasano, H}, title = {Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis.}, journal = {Cancer letters}, volume = {244}, number = {1}, pages = {24-33}, doi = {10.1016/j.canlet.2005.11.038}, pmid = {16427184}, issn = {0304-3835}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; DNA-Binding Proteins/*metabolism ; Female ; Gene Expression Profiling ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/genetics/*metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was negatively correlated with clinical stage, histological grade and HER2 status, and positively associated with sex-steroid receptors, steroidogenic acute regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal carcinoma in situ. These results suggest that LRH-1 is frequently detected in breast carcinoma tissues, and plays important roles including the regulation of in situ steroidogenesis.}, } @article {pmid16425085, year = {2006}, author = {Furuyama, K and Doi, R and Mori, T and Toyoda, E and Ito, D and Kami, K and Koizumi, M and Kida, A and Kawaguchi, Y and Fujimoto, K}, title = {Clinical significance of focal adhesion kinase in resectable pancreatic cancer.}, journal = {World journal of surgery}, volume = {30}, number = {2}, pages = {219-226}, pmid = {16425085}, issn = {0364-2313}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Blotting, Western ; Female ; Focal Adhesion Kinase 1/genetics/*metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/mortality/*pathology/*surgery ; Probability ; Prognosis ; RNA, Neoplasm ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Sensitivity and Specificity ; Statistics, Nonparametric ; Survival Analysis ; }, abstract = {Focal adhesion kinase (FAK) is a non-receptor, cytoplasmic protein tyrosine kinase that is involved in the regulation of cellular signaling, migration, apoptosis, and cell cycle progression. Previous reports have shown that FAK is expressed in various kinds of cancer tissues and cancer cell lines; however, no information is available about human pancreatic carcinoma specimens. Tissue such specimens were obtained from 50 patients who underwent pancreatic resection for pancreatic invasive ductal carcinoma at our institute from 1996 to 2002. Immunohistochemical analysis of FAK was performed in the resected specimens. Focal adhesion kinase expression in seven human pancreatic cancer cell lines was analyzed by reverse transcription polymerase chain reaction (PCR) analysis and Western blot analysis. Focal adhesion kinase expression was detected in 24 of 50 cases (48%). There was a statistically significant correlation between FAK expression and tumor size (P=0.004), although FAK expression did not significantly correlate with other factors such as tumor histological grade, lymph node metastasis, distant metastasis, histological stage, and overall survival. Reverse transcription PCR analysis and Western blot analysis showed that FAK was expressed in all seven pancreatic cancer cell lines. Focal adhesion kinase expression was not directly related to clinicopathological factors except tumor size in pancreatic carcinoma. Focal adhesion kinase expression may not be a prognostic marker for pancreatic cancer patients.}, } @article {pmid16424165, year = {2006}, author = {Devilder, MC and Maillet, S and Bouyge-Moreau, I and Donnadieu, E and Bonneville, M and Scotet, E}, title = {Potentiation of antigen-stimulated V gamma 9V delta 2 T cell cytokine production by immature dendritic cells (DC) and reciprocal effect on DC maturation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {176}, number = {3}, pages = {1386-1393}, doi = {10.4049/jimmunol.176.3.1386}, pmid = {16424165}, issn = {0022-1767}, mesh = {Antigens/immunology ; Antineoplastic Agents/pharmacology ; Calcium/metabolism ; Cell Adhesion/immunology ; Cell Differentiation/*immunology ; Cells, Cultured ; Coculture Techniques ; Cytokines/*biosynthesis ; Dendritic Cells/*cytology/drug effects/*immunology/microbiology ; Diphosphates/pharmacology ; Diphosphonates/pharmacology ; Humans ; Kinetics ; Mycobacterium bovis/immunology ; Pamidronate ; Receptors, Antigen, T-Cell, gamma-delta/*immunology/metabolism ; T-Lymphocytes/*immunology/metabolism ; Th1 Cells/immunology/metabolism ; Th2 Cells/immunology/metabolism ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {Vgamma9Vdelta2 T cells, a major gammadelta PBL subset in human adults, have been previously implicated in dendritic cell (DC) licensing, owing to their high frequency in peripheral tissues and their ability to produce inflammatory cytokines upon recognition of a broad array of conserved Ags. Although these observations implied efficient recognition of Ag-expressing immature DC (iDC) by Vgamma9Vdelta2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that iDC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established Vgamma9Vdelta2 T cell clones and ex vivo memory Vgamma9Vdelta2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate Vgamma9Vdelta2 production of inflammatory cytokines required for their own maturation suggested that Vgamma9Vdelta2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly Vgamma9Vdelta2 cells induced accelerated maturation of Ag-expressing iDC but not "bystander" DC, even within mixed cell populations comprising both Ag-expressing and nonexpressing iDC. Furthermore Vgamma9Vdelta2 cells induced full differentiation into IL-12-producing cells of iDC infected by Vgamma9Vdelta2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory Vgamma9Vdelta2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.}, } @article {pmid16422073, year = {2005}, author = {Liu, R and Fu, F and Shi, X and You, F and Ji, Z and Dong, X}, title = {[Frequency characteristic of diseased breast tissues detected by electrical impedance scanning].}, journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi}, volume = {22}, number = {6}, pages = {1090-1094}, pmid = {16422073}, issn = {1001-5515}, mesh = {Breast Diseases/*diagnosis/pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; *Electric Impedance ; Electronics, Medical/instrumentation/methods ; Female ; Humans ; Hyperplasia/diagnosis ; }, abstract = {The rules of conductance parameters on diseased breast tissue, which change with the driven frequency, are studied by use of electrical impedance scanning. This work is intended to provide a basis for further examination of breast. We have obtained conductance parameters' frequency characteristic of three kinds of breast diseases, i.e. invasive ductal carcinoma, neoplastic hyperplasia, and mastopathia. And by comparison, we find that the frequency characteristic of the diseased breast tissues is different from that of the peripheral normal tissues, and the frequency characteristic shows differences among the three kinds of diseased breast tissues. So, we are able to identify the kind of breast disease by its frequency characteristic.}, } @article {pmid16417224, year = {2006}, author = {Isomura, I and Tsujimura, K and Morita, A}, title = {Antigen-specific peripheral tolerance induced by topical application of NF-kappaB decoy oligodeoxynucleotide.}, journal = {The Journal of investigative dermatology}, volume = {126}, number = {1}, pages = {97-104}, doi = {10.1038/sj.jid.5700027}, pmid = {16417224}, issn = {0022-202X}, mesh = {Animals ; CD4 Antigens/immunology ; Cell Movement/drug effects ; Dendritic Cells/drug effects/immunology ; Hypersensitivity, Delayed/immunology/*prevention & control ; Immune Tolerance ; *Immunosuppression Therapy ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Ointments ; Oligodeoxyribonucleotides/*administration & dosage ; Ovalbumin/immunology ; Receptors, Interleukin-2/immunology ; Skin/drug effects ; T-Lymphocytes, Regulatory/*drug effects/immunology ; }, abstract = {Activation and maturation of dendritic cells (DC) are crucial for the establishment of delayed-type hypersensitivity (DTH). However, antigen presentation by immature DC (iDC) might lead to antigen-specific peripheral tolerance. NF-kappaB plays significant roles in upregulation of co-stimulatory molecules and cytokines in DC and therefore we investigated whether NF-kappaB decoy oligodeoxynucleotide (ODN) might induce tolerance to DTH. NF-kappaB decoy ODN suppressed ovalbumin (OVA)-induced DTH responses not only in naïve but also in presensitized mice. The suppressive effect was found to be antigen-specific. NF-kappaB decoy ODN-induced tolerance involved CD4(+)CD25(+) regulatory T cells (Treg), because in vivo depletion of CD25(+) T cells abrogated the tolerance, whereas adoptive transfer of such T cell population from tolerant mice induced tolerance. Furthermore, the induction of Treg was related to insufficient migration and/or maturation of DC, because a sizable DC population still remained in peripheral tissue even after exposure to exogenous antigen in NF-kappaB decoy ODN-treated mice. Even if they migrated into lymph nodes, they showed insufficient upregulation of co-stimulatory molecules and impaired antigen-specific activation of T cells. Topical application of NF-kappaB decoy ODN might thus be a new approach to induce antigen-specific peripheral tolerance.}, } @article {pmid16410723, year = {2006}, author = {Lo, PK and Mehrotra, J and D'Costa, A and Fackler, MJ and Garrett-Mayer, E and Argani, P and Sukumar, S}, title = {Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer.}, journal = {Cancer biology & therapy}, volume = {5}, number = {3}, pages = {281-286}, doi = {10.4161/cbt.5.3.2384}, pmid = {16410723}, issn = {1538-4047}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Acetylation ; Azacitidine/analogs & derivatives/pharmacology ; Breast/metabolism ; Breast Neoplasms/*genetics ; Cell Line ; Cell Line, Tumor ; *DNA Methylation/drug effects ; Decitabine ; Down-Regulation ; *Epigenesis, Genetic ; Genes, Tumor Suppressor ; Histones/*metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Intracellular Signaling Peptides and Proteins ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Proteins/*genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {Expression of Secreted frizzled related protein 1 (SFRP1), a recently identified tumor suppressor gene encoding a WNT signaling antagonist, has been found to be frequently down-regulated in breast cancer and is associated with disease progression and poor prognosis. Here, we investigated the role of epigenetic silencing of SFRP1 in breast cancer cell lines and primary breast tumors. Through analyses by methylation-specific PCR and bisulfite sequencing, promoter methylation of SFRP1 was detected in 88% (7/8) of breast cancer cell lines, 17% (1/6) of grade 1 of ductal carcinoma in situ (DCIS), 69% (9/13) of grade 2 and 3 of DCIS, 68% (19/28) of invasive ductal carcinomas (IDC) and 33% (6/18) of lobular carcinomas but not in any (0/14) of normal mammoplasty specimens and mammary epithelial organoids examined. Real-time RT-PCR studies indicated that loss or downregulation of SFRP1 expression in tumors is frequently associated with promoter hypermethylation. In addition, breast cancer cell lines with SFRP1 promoter hypermethylation reexpressed SFRP1 mRNA after treatment with 5-azaC, implying that DNA methylation is the predominant epigenetic mechanism for SFRP1 gene silencing. These findings suggest that frequent downregulation of SFRP1 expression in breast cancer can be attributed, in large part, to aberrant promoter hypermethylation in conjunction with or without histone deacetylation. Based on the frequency of tumor-specific hypermethylation in this gene, SFRP1 could provide a valuable marker for breast cancer.}, } @article {pmid16406060, year = {2006}, author = {Goth, SR and Chu, RA and Pessah, IN}, title = {Oxygen tension regulates the in vitro maturation of GM-CSF expanded murine bone marrow dendritic cells by modulating class II MHC expression.}, journal = {Journal of immunological methods}, volume = {308}, number = {1-2}, pages = {179-191}, doi = {10.1016/j.jim.2005.10.012}, pmid = {16406060}, issn = {0022-1759}, support = {P01 ES11269/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation ; Bone Marrow Cells/*cytology/*drug effects/immunology/metabolism ; CD11c Antigen/metabolism ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Separation ; Dendritic Cells/*cytology/*drug effects/immunology/metabolism ; Female ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology ; Histocompatibility Antigens Class II/*metabolism ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Oxygen/metabolism ; Recombinant Proteins ; }, abstract = {Conventional culture conditions for GM-CSF expanded murine bone marrow derived dendritic cells (BMDCs) uses ambient (hyperoxic) oxygen pressure (20% v/v, 152 Torr) and medium supplemented with the thiol 2-mercaptoethanol (2-Me). Given the redox activities of O2 and 2-Me, the effects of 2%, 5%, 10%, and 20% v/v O2 atmospheres and omitting 2-Me from the medium were tested upon the generation of GM-CSF expanded BMDCs. DC yield, phenotype and function were compared to BMDCs grown using conventional conditions. All cultures yielded DC subsets with CD11c+ MHC II(NEG), CD11c+ MHC II(INT), CD11c+ MHC II(HI) expression phenotypes, classed as precursor, immature, and mature DCs (IDC, MDC). Low O2 tensions generated significantly fewer precursor DCs, and more IDCs and MDCs. Cytometer sorted precursor DCs expressed surface class II MHC after transfer to low, but not high O2 atmospheres. Expression of myeloid markers was similar between BMDC cultures generated in 5% O2 or conventional conditions, and MDCs from low O2 cultures had the morphology typical of mature myeloid DCs. IDCs and MDCs from low O2 and conventional culture conditions were similarly potent allostimulatory APCs. The O2 tension (but not 2-Me addition) in vitro significantly influences overall DC subset frequencies and yield, and governs DC maturation by regulating the surface class II MHC expression of GM-CSF expanded BMDC cultures.}, } @article {pmid16405845, year = {2005}, author = {Liu, W and Li, WM and Gao, C and Wang, XR and Li, DM and Sun, NL}, title = {[Relationship of CTLA-4 exon 1 A49-->G polymorphism with sCTLA-4 and Th1/Th2 bias in idiopathic dilated cardiomyopathy].}, journal = {Zhonghua yi xue za zhi}, volume = {85}, number = {45}, pages = {3221-3224}, pmid = {16405845}, issn = {0376-2491}, mesh = {Antigens, CD/blood/*genetics ; Antigens, Differentiation/blood/*genetics ; CTLA-4 Antigen ; Cardiomyopathy, Dilated/blood/*genetics/*immunology ; Case-Control Studies ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interferon-gamma/blood ; Interleukin-4/blood ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; *Polymorphism, Single Nucleotide ; T-Lymphocytes, Helper-Inducer/*immunology ; Th1 Cells/immunology ; Th2 Cells/immunology ; }, abstract = {OBJECTIVE: To investigate the association of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene exon 1 A49-->G polymorphism with the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Chinese Han nationality.

METHODS: Peripheral blood samples were collected from 48 patients with IDC, 31 males and 17 females, and 50 sex- and age-matched normal controls. ELISA was used to examine the cytokines: sCTLA-4, gamma-interferon (IFN-gamma), and interleukin-4 (IL-4)with the ratio of IFN-gamma/IL-4 as an indicator for Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1 A49-->G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4, IFN-gamma and IFN-gamma/IL-4 was evaluated by linear regression analysis.

RESULTS: Compared with the normal controls, the frequencies of GG genotype (0.6042 and 0.7396, P = 0.012) and the G allele (0.36 and 0.56, P = 0.008) were significantly increased in the patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls (1.87 microg/L +/- 1.06 microg/L vs. 0.54 microg/L +/- 0.19 microg/L, P < 0.05). IFN-gamma was significantly lower in the IDC group than in the control group (16 ng/L +/- 6 ng/L vs. 30 ng/L +/- 10 ng/L, P < 0.05). The ratio of IFN-gamma/IL-4 was significantly in the IDC group than in the control group (1.63 +/- 0.50 vs. 3.01 +/- 0.89, P < 0.05). No statistically difference was found in the IL-4 level between the two groups. Linear regression analysis manifested significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4 (r = 0.57, P = 0.021), IFN-gamma/IL-4 ratio (r = 0.42, P = 0.028) in the IDC group. While no correlation was found for AA, AG genotype and the A allele frequency.

CONCLUSION: CTLA-4 gene exon 1 A49-->G substitution is associated with an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene may have a significant role in IDC, possibly via a Thr-->Ala change in CTLA-4 signal peptide, with a result of functional change of sCTLA-4. The bias of Th1/Th2 paradigm is associated with the increased sCTLA-4 level under certain background of immunogenicity.}, } @article {pmid16402338, year = {2006}, author = {Vanden Bempt, I and Vanhentenrijk, V and Drijkoningen, M and De Wolf-Peeters, C}, title = {Comparative expressed sequence hybridization reveals differential gene expression in morphological breast cancer subtypes.}, journal = {The Journal of pathology}, volume = {208}, number = {4}, pages = {486-494}, doi = {10.1002/path.1911}, pmid = {16402338}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Chromosomes, Human, Pair 8 ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Humans ; In Situ Hybridization/methods ; Oligonucleotide Array Sequence Analysis ; }, abstract = {In this study, comparative expressed sequence hybridization (CESH) has been used to compare gene expression patterns in three morphologically different breast cancer subtypes: classic-type invasive lobular carcinoma (ILC), poorly differentiated ERBB2-negative invasive ductal carcinoma-not otherwise specified (IDC-NOS), and poorly differentiated ERBB2-positive IDC-NOS. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridization (CGH). Eight cases of each breast cancer subtype were included in the study. For each subtype, two pools of four cases each were constructed. CESH was used to compare both pools within the same morphological subtype, followed by a comparison of pools belonging to different subtypes. This revealed three chromosomal regions that were differentially expressed in ductal and lobular carcinomas, including relative overexpression at 8q13-q23 and 16q22, and relative underexpression at 8p21-p22. In addition, an expression signature characterized by relative overexpression at 3q24-q26.3, 14q23-31, 17q12, and 20q12-13 was identified for ERBB2-positive IDC-NOS. In summary, CESH analysis highlights chromosomal regions of differential gene expression that are associated with morphologically defined breast cancer subtypes and suggests that regions on chromosome 8 are of interest in the discrimination between ductal and lobular carcinomas. In addition, using CESH, it was possible to identify an ERBB2 expression signature, comprising four chromosomal regions with potential significance in the aggressive behaviour of ERBB2-positive IDC-NOS.}, } @article {pmid16397925, year = {2005}, author = {Izgi, C and Cevik, C and Ozdemir, N and Kaymaz, C and Ozkan, M}, title = {Serum anti-p53 antibodies do not occur in patients with heart failure due to idiopathic dilated and ischemic cardiomyopathies.}, journal = {European journal of heart failure}, volume = {7}, number = {7}, pages = {1095-1098}, doi = {10.1016/j.ejheart.2005.01.015}, pmid = {16397925}, issn = {1388-9842}, mesh = {Adolescent ; Adult ; Aged ; Autoantibodies/*blood ; Biomarkers/blood ; Cardiomyopathy, Dilated/*complications ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart Failure/blood/*etiology/immunology ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*complications ; Tumor Suppressor Protein p53/*immunology ; }, abstract = {BACKGROUND: P53 is a key protein which controls cell cycle arrest and apoptosis in response to DNA damage. Auto-antibodies against p53 have been detected in some cancer patients and also in patients with autoimmune diseases. In these patients, the main cause of anti-p53 antibody occurrence was considered to be increased intracellular p53 protein in cancer cells and autoreactive lymphocytes, respectively. Intracellular p53 also increases with cardiomyocyte apoptosis during heart failure and autoreactive lymphocytes play a role in the course of idiopathic dilated cardiomyopathy (IDC) and ischemic cardiomyopathy (ICM). Based on these observations, we hypothesized that anti-p53 antibody response may also occur in patients with heart failure due to ICM and IDC.

AIM: The aim of this study was to evaluate anti-p53 antibodies in the serum of patients with heart failure due to IDC and ICM.

METHODS: 70 eligible patients with heart failure and severe left ventricular systolic dysfunction (mean fractional shortening 12.03 +/- 3.93%) were included in the study. The aetiology of heart failure was IDC in 26 patients and ICM in 44 patients, according to the angiographic and echocardiographic findings.

RESULTS: Anti-p53 antibodies were not detected in any of the patients.

CONCLUSION: Anti-p53 antibodies do not occur in patients with heart failure due to IDC and ICM, possible explanations are discussed in the text.}, } @article {pmid16381010, year = {2006}, author = {Yeh, YT and Hou, MF and Chung, YF and Chen, YJ and Yang, SF and Chen, DC and Su, JH and Yuan, SS}, title = {Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival.}, journal = {International journal of cancer}, volume = {118}, number = {11}, pages = {2678-2684}, doi = {10.1002/ijc.21707}, pmid = {16381010}, issn = {0020-7136}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Case-Control Studies ; Cell Transformation, Neoplastic ; Female ; Gene Expression Profiling ; Humans ; Immunoblotting ; Mitogen-Activated Protein Kinase 1/biosynthesis ; Mitogen-Activated Protein Kinase 3/biosynthesis ; Mitogen-Activated Protein Kinase 8/*biosynthesis/genetics ; Mitogen-Activated Protein Kinase 9/*biosynthesis/genetics ; Phosphorylation ; Prognosis ; Survival Analysis ; p38 Mitogen-Activated Protein Kinases/biosynthesis ; }, abstract = {Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In this study, we analyzed the expression of p-JNK, as well as p-ERK1/2 and p-38, in the pair of cancer and noncancer breast tissues, by using immunoblotting techniques. These results were further correlated with the clinicopathological characteristics and overall survival. Decreased p-JNK1/2 expression in cancer tissues was observed in 48.5% of breast infiltrating ductal carcinoma (IDC) cases and was correlated significantly with the increased tumor grade and the decreased age at diagnosis (p = 0.030 and 0.029). Interestingly, the Kaplan-Meier survival curve showed that the decreased p-JNK1/2 expression was associated with a better overall survival of IDC (p = 0.004). The expression of p-JNK1/2 was positively correlated with p-p38 (p = 0.002), but not p-ERK1/2. Furthermore, co-expressed p-JNK1/2 and p-p38 was associated with a poor overall survival of IDC (p = 0.007). In conclusion, our results indicate that the aberrant p-JNK1/2 expression and the co-expressed p-JNK1/2 and p-p38 in breast tissues may play a role in the carcinogenesis of breast IDC.}, } @article {pmid16380768, year = {2005}, author = {Meteoglu, I and Dikicioglu, E and Erkus, M and Culhaci, N and Kacar, F and Ozkara, E and Uyar, M}, title = {Breast carcinogenesis. Transition from hyperplasia to invasive lesions.}, journal = {Saudi medical journal}, volume = {26}, number = {12}, pages = {1889-1896}, pmid = {16380768}, issn = {1658-3175}, mesh = {Adult ; Aged ; Apoptosis/physiology ; Biopsy, Needle ; Breast/*pathology ; Breast Neoplasms/*pathology/*physiopathology ; Carcinoma, Ductal, Breast/pathology/physiopathology ; Carcinoma, Intraductal, Noninfiltrating/pathology/physiopathology ; Cell Proliferation ; Cell Transformation, Neoplastic/*pathology ; Female ; Humans ; Hyperplasia/pathology/physiopathology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; Probability ; Sampling Studies ; Statistics, Nonparametric ; Tissue Culture Techniques ; }, abstract = {OBJECTIVES: To examine the balance loss between proliferation and apoptosis that play a role in breast cancer development, and to explore the places of various genes and molecules within this process in this supposed multistep process.

METHODS: We obtained the specimens from 40 patients between 2002 and 2004 at the Department of Pathology, Medical Faculty, Adnan Menderes University, Aydin, Turkey. We categorized the lesions ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), in situ ductal carcinoma (DCIS), and invasive ductal carcinoma (IDC). We determined the tumor size, histological grade and lymph node status of invasive cases and we used nottingham prognostic index (NPI). We applied ER, PR, c-erbB2, p53, Ki-67, bcl-2, dUTP nick end labeling (TUNEL), breast cancer gene-1, matrix metalloproteinases-1 and tissue inhibitor matrix metalloproteinases-1 stains to each lesion using the immunohistochemical method.

RESULTS: We observed that ER and PR decreased in ADH when compared with DH (p=0.0001 and p=0.019). However, we determined that in DCIS as c-erbB2 (p=0.005) and Ki-67 (p=0.004) increase, TUNEL (p=0.04) and bcl-2 (p=0.005) decrease, when compared with ADH. When compared with DCIS lesions, we observed the existence of a higher c-erbB2 (p=0.003) and a lower TUNEL (p=0.012) in invasive tumors. Furthermore, we found that there is a higher MMP-1 (p=0.04) in invasive lesions, when compared with non-invasive lesions. We detected higher PR (p=0.049), lower TUNEL and c-erbB2 (p=0.017) in low grade group of NPI, when compared with high grade group of NPI.

CONCLUSION: As a result, it has been shown that together with increase in proliferation, decrease in apoptosis, too, contributes to the proliferation/apoptosis imbalance that occurs in breast carcinogenesis. Increase in proliferation and decrease in apoptosis are parallel with the progression of lesions. We also showed that the changes, beginning with loss of ER and PR in ADH step, can cause malign transformation, which is especially notable both in DCIS step due to Ki-67 and c-erbB2 increase, and also with bcl-2 and TUNEL decrease.}, } @article {pmid16378281, year = {2002}, author = {Soyuer, I and Ekinci, C and Kaya, M and Bahar, K}, title = {The value of fine needle aspiration biopsy in the diagnosis of metastatic liver tumours.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {13}, number = {2}, pages = {78-82}, pmid = {16378281}, issn = {1300-4948}, abstract = {BACKGROUND/AIMS: Fine needle aspiration biopsy is a useful tool in the diagnosis of primary malignancies and metastatic lesions of the liver. The aim of this study was to determine the types and features of tumors diagnosed by this method and the difficulties in differential diagnosis.

METHODS: Fine needle aspiration biopsy smears from 704 patients with metastatic liver lesions were reviewed.

RESULTS: Among the metastastatic carcinomas in which their primary origin was identified, pulmonary carcinomas were the largest group. While colon adenocarcinoma was most prevalent (21.65%) where the primary origin of metastatic tumors was identified, followed by breast carcinoma (20.10%) and gastric adenocarcinoma (19.59%). The cases which cannot be differentiated from hepatocellular carcinoma in cytologic examination are invasive ductal carcinoma, renal cell carcinoma and squamous cell carcinoma.

CONCLUSIONS: Pulmonary and colon carcinomas are the common metastatic tumors of the liver.}, } @article {pmid16378230, year = {2005}, author = {Tsuchiya, S and Li, F}, title = {Electron microscopic findings for diagnosis of breast lesions.}, journal = {Medical molecular morphology}, volume = {38}, number = {4}, pages = {216-224}, pmid = {16378230}, issn = {1860-1480}, mesh = {Breast/pathology/ultrastructure ; Breast Neoplasms/*diagnosis/pathology/*ultrastructure ; Female ; Humans ; }, abstract = {The normal mammary gland can be roughly divided into the large duct close to the nipple and the terminal duct located within the lobulus. Both the large duct and the terminal duct are composed of epithelial cells and myoepithelial cells. The epithelial cells can be divided into light and dark cells using electron density. Heterochromatin is the predominant type of chromatin found in normal mammary glands. The cytoplasm of myoepithelial cells contains a number of fine filaments that possess dense patches. The myoepithelial cells of the large duct have a large process with a crablike appearance that protrudes from the cytoplasm. The myoepithelial cells of the terminal duct, by contrast, assume a relatively flat form and are approximately parallel to the epithelial-stromal junction. If the nuclei of the epithelial cells of normal mammary glands and benign breast lesions are compared with those of malignant breast lesions, the latter are primarily oval or circular in shape whereas the former often show marked notches. The predominant chromatin is heterochromatin in noncancer cells and euchromatin in cancer cells. The intracytoplasmic lumen (ICL) can be roughly divided into two types. The ICL is frequently seen in breast cancers, especially scirrhous carcinoma and lobular carcinoma. Invasive ductal carcinoma can be divided into three types: papillotubular carcinoma, solid-tubular carcinoma, and scirrhous carcinoma. Scirrhous carcinoma can be divided into two subtypes: scirrhous carcinoma in the broader sense of the term (characterized by scirrhous invasion of the stroma by papillotubular carcinoma or solid-tubular carcinoma), and scirrhous carcinoma in the narrower sense of the term (characterized by linear or cluster-like invasion of the stroma without forming ducts). Ultrastructural characteristics of scirrhous carcinoma in the narrow sense are bright cytoplasm (seen in most cells) and euchromatin (seen in all cells of this type of carcinoma). In cases of papillotubular carcinoma, solid-tubular carcinoma, and scirrhous carcinoma in the broad sense, euchromatin is predominant but sporadic cells with heterochromatin are also seen. Adenoid cystic carcinoma and carcinoid tumor of the breast are histological types of breast carcinoma that show characteristic features under an electron microscope. Ultrastructurally, the former shows a pseudocyst and true lumen whereas the latter presents numerous neuroendocrine granules within the cytoplasm. Breast carcinoma shows several ultrastructural characteristics that are useful in differential diagnosis. Therefore, it is advisable to take electron microscopic findings into account when evaluating or diagnosing breast lesions.}, } @article {pmid16372244, year = {2006}, author = {García-Caballero, T and Menéndez, MD and Vázquez-Boquete, A and Gallego, R and Forteza, J and Fraga, M}, title = {HER-2 status determination in breast carcinomas. A practical approach.}, journal = {Histology and histopathology}, volume = {21}, number = {3}, pages = {227-236}, doi = {10.14670/HH-21.227}, pmid = {16372244}, issn = {1699-5848}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*chemistry/drug therapy/genetics ; Carcinoma, Ductal, Breast/*chemistry/drug therapy/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/genetics ; Humans ; Immunohistochemistry/*methods ; In Situ Hybridization, Fluorescence/*methods ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis/genetics ; Reproducibility of Results ; Trastuzumab ; }, abstract = {Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression/gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.}, } @article {pmid16367904, year = {2005}, author = {Mitsunaga, S and Hasebe, T and Iwasaki, M and Kinoshita, T and Ochiai, A and Shimizu, N}, title = {Important prognostic histological parameters for patients with invasive ductal carcinoma of the pancreas.}, journal = {Cancer science}, volume = {96}, number = {12}, pages = {858-865}, doi = {10.1111/j.1349-7006.2005.00128.x}, pmid = {16367904}, issn = {1347-9032}, mesh = {Aged ; Carcinoma, Ductal/mortality/*pathology/surgery ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatectomy ; Pancreatic Neoplasms/mortality/*pathology/surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; Time Factors ; }, abstract = {For clinicians, the orthodox histological investigation of patients with invasive ductal carcinoma (IDC) remains important for predicting prognoses. The purpose of the present study was to determine the most important of the known prognostic histological parameters (including fibrotic focus and tumor necrosis), enabling the outcomes of 101 patients with IDC of the pancreas to be predicted accurately. Furthermore, we established a scoring classification consisting of important prognostic histological parameters examined in this study. Multivariate survival analyses showed that invasive tumor size of more than 3 cm, the presence of tumor necrosis, the presence of nerve plexus invasion and lymph vessel invasion scores of 2 or 3 were important prognostic factors. Our scoring classification, consisting of the above four parameters, accurately classified the outcome of patients independent of the invasive tumor size of IDC. We concluded that invasive tumor size of 3 cm or more, the presence of tumor necrosis, the presence of nerve plexus invasion and lymph vessel invasion scores of 2 or 3 are important histological prognostic parameters for patients with IDC of the pancreas. Furthermore, the scoring system consisting of the above four histological parameters is probably a very useful prognostic histological classification for patients with IDC of the pancreas.}, } @article {pmid16364645, year = {2006}, author = {Haraguchi, M and Kuroki, T and Tsuneoka, N and Furui, J and Kanematsu, T}, title = {Management of chylous leakage after axillary lymph node dissection in a patient undergoing breast surgery.}, journal = {Breast (Edinburgh, Scotland)}, volume = {15}, number = {5}, pages = {677-679}, doi = {10.1016/j.breast.2005.11.004}, pmid = {16364645}, issn = {0960-9776}, mesh = {Aged ; Axilla ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Chylous Ascites/*diagnosis/etiology/surgery ; Diagnosis, Differential ; Female ; Humans ; Lymph Node Excision/*adverse effects ; Lymphatic Vessels/*surgery ; Mastectomy/adverse effects ; Postmenopause ; Postoperative Complications/*diagnosis/etiology/surgery ; Reoperation ; Suction ; }, abstract = {A 71-year old woman who underwent a modified radical mastectomy for invasive ductal carcinoma of the left breast, developed postoperative chylous leakage. Though conservative management was uneffective, a direct surgical repair led to good results. Because the morbidity of a reoperation to the superficial chest wall is low, timely surgical treatment is therefore strongly recommended in cases of high output chylous leakage following a mastectomy.}, } @article {pmid16360363, year = {2005}, author = {Sampietro, T and Neglia, D and Bionda, A and Dal Pino, B and Bigazzi, F and Puntoni, M and Startari, U and Morales, A and Minichilli, F and Bianchi, F and L'Abbate, A}, title = {Inflammatory markers and serum lipids in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {96}, number = {12}, pages = {1718-1720}, doi = {10.1016/j.amjcard.2005.07.093}, pmid = {16360363}, issn = {0002-9149}, mesh = {Adult ; Aged ; Biomarkers/blood ; C-Reactive Protein/*metabolism ; Cardiomyopathy, Dilated/*blood/complications/immunology ; Ceruloplasmin/metabolism ; Cholesterol, HDL/*blood ; Complement C3/metabolism ; Complement C4/metabolism ; Disease Progression ; Dyslipidemias/blood/complications/immunology ; E-Selectin/blood ; Female ; Haptoglobins/metabolism ; Humans ; Immunity, Innate/physiology ; Inflammation/blood ; Intercellular Adhesion Molecule-1/blood ; Male ; Middle Aged ; Prognosis ; Risk Factors ; Triglycerides/*blood ; }, abstract = {Coronary microcirculation is impaired in idiopathic dilated cardiomyopathy (IDC), possibly because of endothelial dysfunction. High-density lipoproteins (HDLs) have the potential to regulate endothelial function and modulate inflammation and the innate immune response. This study investigated whether reduced HDLs, concomitantly with the activation of inflammation, are associated with IDC. Fifty-five patients with IDC, without evidence of other organ or systemic, chronic, or recurrent diseases, were compared with 55 healthy controls for HDLs and complete lipid profiles, C-reactive protein, C3 and C4 complement fractions, soluble intercellular adhesion molecule-1 and soluble endothelial leukocyte adhesion molecule-1, haptoglobin, and ceruloplasmin. Patients with IDC differed from controls, with lower HDL levels, lower apolipoprotein A-I and A-II levels, and higher triglyceride levels, but not on total and low-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein(a). In addition, all measured inflammation markers were significantly greater in patients with IDC than in controls and were negatively correlated with HDLs. A strong and independent association with IDC was found for age, soluble intercellular adhesion molecule-1, and HDLs that, when categorized as <40 or >40 mg/dl, showed the strongest association (prevalence odds ratio 0.10, p <0.0005) with the disease. In conclusion, the data here reported on reduced HDLs and increased endothelial inflammatory activation and the linear negative correlation between HDLs and inflammation markers, particularly soluble intercellular adhesion molecule-1, could suggest a role for HDLs in the endothelial-microvascular dysfunction seen in IDC.}, } @article {pmid16351611, year = {2005}, author = {Rotstein, AH and Neerhut, PK}, title = {Ultrasound characteristics of histologically proven grade 3 invasive ductal breast carcinoma.}, journal = {Australasian radiology}, volume = {49}, number = {6}, pages = {476-479}, doi = {10.1111/j.1440-1673.2005.01515.x}, pmid = {16351611}, issn = {0004-8461}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; *Ultrasonography, Mammary ; }, abstract = {High-grade invasive ductal carcinoma (IDC) may paradoxically display features similar to benign breast masses. This study analysed the ultrasound features of histologically proven cases of grade 3 IDC. At North Western BreastScreen Victoria, from 4 February 1993 to 30 September 2002, 181 cases of grade 3 IDC that had ultrasound evaluation were available for retrospective analysis. For each tumour, four features were assessed: margin, attenuation characteristics, echotexture and depth versus width ratio. Eighty-seven per cent of tumours had an aggressive margin with an echogenic rind, microlobulation or angular margins. However, 11% had a well-defined smooth margin. The classic sonographic malignant feature of posterior shadowing was present in only 30%, whereas the tissues posterior to the lesion remained isoechoic in 48% and showed posterior enhancement in 11%. Six per cent of the tumours were isoechoic and difficult to appreciate on ultrasound. The best feature to characterize lesions as malignant was the margin of the lesion. To ensure that malignant lesions are correctly categorized, it is important that interfaces between the tumour and adjacent breast parenchyma are meticulously evaluated in a real-time fashion rather than viewed as a single still image.}, } @article {pmid16338494, year = {2005}, author = {Chang, CC and Satwani, P and Oberfield, N and Vlad, G and Simpson, LL and Cairo, MS}, title = {Increased induction of allogeneic-specific cord blood CD4+CD25+ regulatory T (Treg) cells: a comparative study of naïve and antigenic-specific cord blood Treg cells.}, journal = {Experimental hematology}, volume = {33}, number = {12}, pages = {1508-1520}, doi = {10.1016/j.exphem.2005.09.002}, pmid = {16338494}, issn = {0301-472X}, support = {5P-30CA13697/CA/NCI NIH HHS/United States ; }, mesh = {Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Coculture Techniques ; Dendritic Cells/immunology ; Fetal Blood/*immunology ; Graft vs Host Disease/etiology/immunology ; Humans ; Isoantigens/*immunology ; Lymphocyte Activation/*immunology ; Models, Biological ; T-Cell Antigen Receptor Specificity/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Transplantation Immunology ; }, abstract = {OBJECTIVE: The genetic and immunological mechanism(s) responsible for the significant decrease in the incidence of graft-vs-host disease (GVHD) following HLA-disparate unrelated cord blood transplantation remains largely unknown. In this study, we investigated if cord blood (CB) CD4(+)CD25(+) T cells play a significant role in reducing the immune responses of allo-reactive CD4(+)CD25(-) T lymphocytes.

METHODS: We compared CB CD4(+)CD25(-) and CD4(+)CD25(+) T cells, either naïve or antigenic stimulated, to their counterparts in unmobilized adult peripheral blood (APB) with respect to genetic expression patterns, immunophenotype, suppressive activity, and mechanism(s) of suppression.

RESULTS: Both naïve CB and APB CD4(+)CD25(+) T cells expressed similarly elevated mRNA levels of CTLA-4, GITR, Foxp3, CD25, and elevated protein levels of CTLA-4 (p < 0.001) and GITR (p < 0.001). However, only naïve APB but not CB CD4(+)CD25(+) T cells showed suppression of allogeneic responses. Stimulation of CD4(+)CD25(-) T cells by MUTZ-iDC (MUTZ-3-specific immature dendritic cells) elicited amplification of these genes and potent suppression (69% +/- 5% and 71% +/- 3% suppression, p < 0.001, CB and APB, respectively) on CD4(+)CD25(-) T cell proliferation induced by MUTZ-iDC but not by unrelated stimulators. Compared to that from unmobilized APB, a significantly higher percentage (2.7-fold +/- 0.5-fold; p < 0.002) of CD4(+)CD25(+)CTLA-4(+) T regulatory (Treg) cell subsets were induced from CB CD4(+)CD25(-) T cells following allogeneic stimulation.

CONCLUSION: Our results suggest that CB CD4(+)CD25(+) Treg cells, which are induced at a higher rate by allogeneic stimulation when compared to unmobilized APB, can readily function as potent allogeneic immune suppressors and may in part contribute to the decrease in CB alloantigen recognition and activation of CB CD4(+)CD25(-) T cells.}, } @article {pmid16328121, year = {2005}, author = {Haberstich, R and Tuech, JJ and Wilt, M and Rodier, JF}, title = {Anal localization as first manifestation of metastatic ductal breast carcinoma.}, journal = {Techniques in coloproctology}, volume = {9}, number = {3}, pages = {237-238}, doi = {10.1007/s10151-005-0235-0}, pmid = {16328121}, issn = {1123-6337}, mesh = {Aged ; Anastrozole ; Anus Neoplasms/pathology/*secondary/*therapy ; Biopsy, Needle ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology/*secondary/surgery ; Chemotherapy, Adjuvant ; Colectomy/methods ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Nitriles/*administration & dosage ; Rare Diseases ; Risk Assessment ; Treatment Outcome ; Triazoles/*administration & dosage ; }, abstract = {The incidence of extrahepatic gastrointestinal metastases from breast cancer is reported in the literature only as necroscopy studies (6-18%); they usually originate from lobular or a mixed ductal-lobular subtype. Nonspecific presenting symptoms, death of the patients caused by other more frequent metastases, and variable radiographic features mimicking primary neoplasms cause a clinical underestimation of this pathology. We report here a case of rectal metastasis from an invasive ductal carcinoma (IDC). This is to our knowledge, the first recorded instance of an anal metastasis from IDC.}, } @article {pmid16324201, year = {2005}, author = {Park, SS and Kim, JE and Kim, YA and Kim, YC and Kim, SW}, title = {Caveolin-1 is down-regulated and inversely correlated with HER2 and EGFR expression status in invasive ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {47}, number = {6}, pages = {625-630}, doi = {10.1111/j.1365-2559.2005.02303.x}, pmid = {16324201}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Cadherins/analysis/metabolism ; Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology ; Case-Control Studies ; Caveolin 1/*analysis/genetics/metabolism ; *Down-Regulation ; ErbB Receptors/analysis/metabolism ; Female ; Genes, erbB-1 ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/metabolism ; Microarray Analysis ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/analysis/metabolism ; Receptors, Progesterone/analysis/metabolism ; Tumor Suppressor Protein p53/analysis/metabolism ; beta Catenin/analysis/metabolism ; }, abstract = {AIMS: To evaluate the caveolin-1 status of invasive ductal carcinoma and its correlation with other important parameters of breast carcinogenesis. Caveolin-1, the main structural protein of caveolae, is involved in the regulation of several intracellular signalling pathways and also functions as a tumour suppressor in breast carcinogenesis.

METHODS AND RESULTS: One hundred and thirty cases of invasive ductal carcinomas with matched normal breast tissue were evaluated immunohistochemically for caveolin-1 expression. Using a tissue microarray, caveolin-1 expression was also correlated with the expression of other antigens such as eostrogen receptor, progesterone receptor, epidermal growth factor receptor (EGFR), HER2, beta-catenin, E-cadherin, p53, Ki67 and with clinicopathological parameters. Immunohistochemical results showed strong expression of caveolin-1 in all normal breast epithelial cells, but a reduction of caveolin-1 expression in 56 cases (43.1%) of invasive ductal carcinoma. Furthermore, a statistically significant inverse correlation between caveolin-1 and EGFR and HER2 was noted (P < 0.001).

CONCLUSIONS: Our results indicate a reduction in caveolin-1 expression in invasive ductal carcinoma of the breast, which supports in vitro studies of its role as a tumour suppressor. Caveolin-1 also shows an inverse correlation with EGFR and HER2, which fits with its function as a negative regulator of signal transduction.}, } @article {pmid16322898, year = {2006}, author = {Oliveira, VM and Piato, S and Silva, MA}, title = {Correlation of cyclooxygenase-2 and aromatase immunohistochemical expression in invasive ductal carcinoma, ductal carcinoma in situ, and adjacent normal epithelium.}, journal = {Breast cancer research and treatment}, volume = {95}, number = {3}, pages = {235-241}, doi = {10.1007/s10549-005-9010-1}, pmid = {16322898}, issn = {0167-6806}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aromatase/*metabolism ; Biomarkers, Tumor ; Breast/pathology ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; Cyclooxygenase 2/*metabolism ; Epithelium/enzymology/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Membrane Proteins/*metabolism ; Middle Aged ; Neoplasm Invasiveness/*pathology ; }, abstract = {The purpose of our study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and aromatase immunohistochemical expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast, as well as in adjacent stroma and normal epithelium, we still correlated with nuclear grade, histologic grade, presence or absence of comedonecrosis, tumor size, and age at diagnosis. Forty-seven cases were evaluated through the use of anti-aromatase and anti-COX-2 polyclonal antibodies. Making the correlation of COX-2 and aromatase expression, we observed that COX-2 expression in IDC was correlated with aromatase expression in IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.024), and stroma tumor (p < 0.001). When the correlation was made between COX-2 expression in DCIS with aromatase, we observed positive correlation in IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.013), and stroma tumor (p < 0.001). In the correlative analysis of COX-2 expression in normal epithelium with aromatase in different evaluated tissues, we observed the following statistical results: IDC (p < 0.001), DCIS (p < 0.001), normal epithelium (p = 0.005), and stroma tumor (p = 0.047). Our results demonstrate the high correlation between COX-2 and aromatase expression in IDC, DCIS and normal epithelium, showing the importance of these two enzymes in the induction, promotion and progression of breast cancer.}, } @article {pmid16316732, year = {2006}, author = {Gökalp, G and Topal, U}, title = {MR imaging in probably benign lesions (BI-RADS category 3) of the breast.}, journal = {European journal of radiology}, volume = {57}, number = {3}, pages = {436-444}, doi = {10.1016/j.ejrad.2005.10.004}, pmid = {16316732}, issn = {0720-048X}, mesh = {Breast/*pathology ; Breast Diseases/*diagnosis ; Breast Neoplasms/diagnosis ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To investigate the role of dynamic magnetic resonance (MR) imaging in the evaluation of probably benign lesions (BI-RADS category 3) and its contribution to patient management.

MATERIALS AND METHODS: Dynamic breast MR imaging was performed in 56 lesions assessed as probably benign in mammography of 43 patients. In MR imaging, T2-weighted turbo spin echo (TSE) with fat suppression sequence followed by pre- and post-contrast T1-weighted 3D-FLASH sequences were used. MR imaging findings were scored using 0-2 point criterion scale. The lesions were divided into five groups according to their total score (0 point: group 1, negative; 1-2 points: group 2, benign; 3 points: group 3, probably benign; 4-5 points: group 4, suspicious for malignancy; 6-8 points: group 5, highly suggestive of malignancy). Histopathologic verification of lesions in group 4 and above was obtained. Lesions in group 3 were either biopsied or followed up by mammography or MR imaging. Lesions in group 1-2 were followed by mammography of 6-month intervals for 2 years. The sensitivity, specificity, accuracy, and positive and negative predictive values of MR imaging in the determination of malignancy in BI-RADS category 3 lesions were calculated.

RESULTS: Fifty-six findings (45 mass, 9 breast tissue, 2 focal enhancement) in 43 patients were detected in MR imaging. According to their total score, 41 lesions (73.2%) and breast tissue had 0 point (group 1); 10 lesions (17.8%) had 1-2 points (group 2); 2 lesions (3.6%) had 3 points (group 3); 2 lesions (3.6%) had 4 and 5 points (group 4); and 1 lesion (1.8%) had 6 points (group 5). Ten lesions (of six in groups 1 and 2, one in group 3, three in groups 4 and 5) were histopathologically confirmed. Out of 10 lesions, only 1 (1.8%) with 4 points in group 4 was diagnosed as invasive ductal carcinoma. Other lesions followed with mammography or MR imaging did not change. The sensitivity, specificity, accuracy, positive and negative predictive values of MR imaging in the determination of malignancy in BI-RADS category 3 lesions were calculated as 100, 96.4, 96.4, 33.3, and 100%, respectively.

CONCLUSION: In the evaluation of BI-RADS category 3 lesions, dynamic MR imaging does not provide additional information with low positive predictive value similar to that of short interval mammography follow-up.}, } @article {pmid16315943, year = {2005}, author = {Sakurai, K and Enomoto, K and Amano, S and Kitajima, A and Suzuki, M and Matsuo, S and Sakamoto, A and Kashio, M and Tani, M and Negishi, N}, title = {[A case of advanced breast cancer with multiple lung and liver metastases successfully treated with multi-disciplinary therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {32}, number = {11}, pages = {1792-1794}, pmid = {16315943}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal/pathology/secondary/*therapy ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Liver Neoplasms/*secondary/*therapy ; Lung Neoplasms/*secondary/*therapy ; Middle Aged ; Taxoids/administration & dosage ; Trastuzumab ; Treatment Outcome ; }, abstract = {We report a case of advanced breast cancer with multiple lung and liver metastases (T4bN1M1) achieving a significant improvement of QOL by multi-disciplinary therapy. The patient was a 63-year-old woman with slight jaundice who had ascites and an ulcerative breast lump with multiple lung and liver metastases. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although the ascites and the jaundice disappeared after chemotherapy, the response for breast tumor, metastatic sites in the lung and the liver were less satisfactory. Fifteen-months later, she received radiation therapy so that metastasis in the brain was recognized. But she had no neurological symptoms. Multi-disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.}, } @article {pmid16311351, year = {2005}, author = {Shien, T and Tashiro, T and Omatsu, M and Masuda, T and Furuta, K and Sato, N and Akashi-Tanaka, S and Uehara, M and Iwamoto, E and Kinoshita, T and Fukutomi, T and Tsuda, H and Hasegawa, T}, title = {Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation.}, journal = {Journal of clinical pathology}, volume = {58}, number = {12}, pages = {1299-1304}, pmid = {16311351}, issn = {0021-9746}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/pathology ; Cell Differentiation ; Disease-Free Survival ; ErbB Receptors/*metabolism ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Myoepithelioma/*diagnosis/metabolism/pathology ; Neoplasm Proteins/metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIMS: To evaluate the expression of common biological markers and the epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation (DCMDs).

MATERIALS/METHODS: Thirty DCMDs were clinicopathologically and immunohistochemically analysed and compared with 36 control cases of high grade conventional invasive ductal carcinoma (IDC).

RESULTS: EGFR, HER2/neu, oestrogen receptor, progesterone receptor, and p53 expression was seen in 21, one, three, four, and 20 of the 30 DCMDs, compared with eight, nine, 18, 17, and five of the 36 conventional IDCs (p<0.05), respectively. In 16 of the 30 DCMDs, metastases were found in the brain, lung, bone, and liver, within a maximum of 47 months (mean, 13.9) after initial surgery, whereas only four of the 36 conventional IDCs metastasised to the lung and bone within a maximum of 27 months (mean, 18.0) after initial surgery (p=0.0001). There was a significant difference in disease free survival between DCMD and conventional IDC (p=0.001). EGFR was frequently overexpressed in DCMD compared with conventional IDC, whereas the expression of HER2/neu and hormone receptors was lower in DCMD. Fluorescent in situ hybridisation revealed that the mean EGFR to chromosome 7 centromere (CEP7) ratio of the 24 DCMD cases available for evaluation was 1.03, and EGFR gene amplification was not detected in the 21 DCMD cases with EGFR overexpression.

CONCLUSION: Immunohistochemistry for myoepithelial markers and EGFR is useful for the accurate diagnosis and molecular target treatment of high grade DCMD.}, } @article {pmid16308473, year = {2005}, author = {Hwang, HG and Choi, HJ and Lee, BI and Yoon, HK and Nam, SH and Choi, HK}, title = {Multi-resolution wavelet-transformed image analysis of histological sections of breast carcinomas.}, journal = {Cellular oncology : the official journal of the International Society for Cellular Oncology}, volume = {27}, number = {4}, pages = {237-244}, doi = {10.1155/2005/526083}, pmid = {16308473}, issn = {1570-5870}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating ; Discriminant Analysis ; Female ; Humans ; *Image Processing, Computer-Assisted ; Neural Networks, Computer ; }, abstract = {Multi-resolution images of histological sections of breast cancer tissue were analyzed using texture features of Haar- and Daubechies transform wavelets. Tissue samples analyzed were from ductal regions of the breast and included benign ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (CA). To assess the correlation between computerized image analysis and visual analysis by a pathologist, we created a two-step classification system based on feature extraction and classification. In the feature extraction step, we extracted texture features from wavelet-transformed images at 10x magnification. In the classification step, we applied two types of classifiers to the extracted features, namely a statistics-based multivariate (discriminant) analysis and a neural network. Using features from second-level Haar transform wavelet images in combination with discriminant analysis, we obtained classification accuracies of 96.67 and 87.78% for the training and testing set (90 images each), respectively. We conclude that the best classifier of carcinomas in histological sections of breast tissue are the texture features from the second-level Haar transform wavelet images used in a discriminant function.}, } @article {pmid16307158, year = {2005}, author = {Brooksbank, R and Woodiwiss, AJ and Sliwa, K and Badenhorst, D and Deftereos, D and Wadee, AA and Essop, MR and Sareli, P and Norton, GR}, title = {Endotoxin-independent white cell cytokine production in haemodynamically stable patients with idiopathic dilated cardiomyopathy.}, journal = {Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners}, volume = {16}, number = {5}, pages = {260-265}, pmid = {16307158}, mesh = {Cardiomyopathy, Dilated/*blood ; Endotoxins/*pharmacology ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; In Vitro Techniques ; Leukocytes/*metabolism ; Lymphotoxin-alpha/blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/analysis/*biosynthesis ; }, abstract = {INTRODUCTION: In heart failure, increased circulating white cell tumour necrosis factor-alpha production could be attributed to elevated plasma endotoxin concentrations or an increase in white cell sensitivity to endotoxin.

AIMS: To ascertain whether, in patients with IDC, circulating white cell TNF-alpha production is also mediated through endotoxin-independent mechanisms.

METHODS: Whole blood production of TNF-alpha, both with and without the presence of an endotoxin stimulus, was evaluated in 89 controls and in 60 patients with IDC in New York Heart Association functional class I, II or III heart failure and without evidence of oedema, reduced peripheral perfusion or elevated plasma endotoxin concentrations. Circulating concentrations of selected pro and anti-inflammatory factors were also measured.

RESULTS: In patients compared to controls, IgG (p < 0.01) (IgG1 and IgG3), but not IgM concentrations were elevated, and plasma TNF-alpha and TGF-beta concentrations were raised (p < 0.001, p < 0.02 respectively). In addition, endotoxin-free cultured whole blood TNF-alpha production (p < 0.0005) was increased. Against a role for endotoxin-mediated pre-activation of white cells in patients, the sensitivity of white cells to endotoxin, as determined from the excitatory endotoxin concentration producing 50% maximal TNF-alpha production was unchanged. Moreover, in favour of non-endotoxin-mediated white cell activation, the calcineurin inhibitor, cyclosporin-A, which did not alter endotoxin-induced TNF-alpha production, decreased TNF-alpha produced by unstimulated cultured cells in patients to values not significantly greater than those in controls.

CONCLUSIONS: We concluded that circulating white cell cytokine over-production can occur through both endotoxin- dependent and -independent mechanisms in IDC.}, } @article {pmid16295319, year = {2004}, author = {Stăvaru, C and Caplanus, A and Radu, DL}, title = {Phenotypical changes during in vitro cultivation of monocytes derived immature dendritic cells.}, journal = {Roumanian archives of microbiology and immunology}, volume = {63}, number = {1-2}, pages = {35-46}, pmid = {16295319}, issn = {1222-3891}, mesh = {Antigens, CD/metabolism ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/*cytology/*physiology ; Flow Cytometry ; Granulocytes/immunology/metabolism ; HLA-DR Antigens/metabolism ; Humans ; Luminescence ; Monocytes/*cytology ; Phenotype ; Reactive Oxygen Species/metabolism ; }, abstract = {Dendritic cells (DC) form a link between the first line of host defence and cellular immunity. In the present study we investigated the effect of cultivation time in generation of immature dendritic cells (iDCs) in vitro from human peripheral blood (PB) monocytes and the influence of iDCs on the oxygen free radicals (OFR) release by polymorphonuclear granulocytes (PMN) stimulated with opsonized zymozan (OZ) and concanavalin A (ConA). Our data suggest that the differentiation in vitro of PB monocytes in iDCs is influenced by the health status of the cell donor, and more by the concentration of cytokines GM-CSF and IL-4 in the system than by the time of cultivation. The in vitro experiments performed demonstrated the interactions between iDC and PMN granulocytes, evaluated by enhanced release of OFR.}, } @article {pmid16292947, year = {2005}, author = {Shah, N and Gibbs, J and Wolverton, D and Cerussi, A and Hylton, N and Tromberg, BJ}, title = {Combined diffuse optical spectroscopy and contrast-enhanced magnetic resonance imaging for monitoring breast cancer neoadjuvant chemotherapy: a case study.}, journal = {Journal of biomedical optics}, volume = {10}, number = {5}, pages = {051503}, doi = {10.1117/1.2070147}, pmid = {16292947}, issn = {1083-3668}, support = {P41RR01192/RR/NCRR NIH HHS/United States ; U54CA105480/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*diagnosis/*drug therapy ; Carcinoma, Ductal/*diagnosis/*drug therapy ; Chemotherapy, Adjuvant ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement/methods ; Lasers ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Prognosis ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrum Analysis/*methods ; Subtraction Technique ; Treatment Outcome ; }, abstract = {Monitoring tumor response to therapy can enable assessment of treatment efficacy, maximizing patient outcome and survival. We employ a noninvasive, handheld laser breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma. DOS measurements are used to quantify bulk tissue optical and physiological parameters, which are mapped to T2- and T1-weighted cMRI images. Initial DOS measurements show high tumor/normal contrast in total hemoglobin concentration (THC, 56+/-7 versus 27+/-4 microM) and water fraction (81.4+/-1% versus 24+/-3%) colocalized with regions of strongly enhancing T2-weighted and cMRI signals. After the fourth cycle of chemotherapy, we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent lesion volume (21.9 versus 13.7 cm3), which corresponds to physiological changes measured by DOS, including a 20 to 25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus 23.4 microM). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.}, } @article {pmid16288397, year = {2005}, author = {Perencevich, EN and Harris, AD and Kaye, KS and Bradham, DD and Fisman, DN and Liedtke, LA and Strausbaugh, LJ and , }, title = {Physicians' acceptable treatment failure rates in antibiotic therapy for coagulase-negative staphylococcal catheter-associated bacteremia: implications for reducing treatment duration.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {41}, number = {12}, pages = {1734-1741}, doi = {10.1086/498116}, pmid = {16288397}, issn = {1537-6591}, support = {K23 AI01752-01A1/AI/NIAID NIH HHS/United States ; U50/CCU112346/CC/ODCDC CDC HHS/United States ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy/*microbiology ; *Catheterization ; *Equipment Contamination ; Humans ; *Practice Patterns, Physicians' ; Staphylococcal Infections/*drug therapy/*microbiology ; Surveys and Questionnaires ; Time Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Decreasing the duration of antimicrobial therapy is an attractive strategy for delaying the emergence of antimicrobial resistance. Limited data regarding optimal treatment durations for most clinical infections hinder the adoption of this approach and impair optimal physician-patient communication under the shared decision-making model. We aimed to identify acceptable failure rates among infectious disease consultants (IDCs) for treatment of central venous catheter-associated bacteremia.

METHODS: A case scenario involving a representative patient who developed central venous catheter-associated bacteremia caused by coagulase-negative staphylococci and who received standard-of-care therapy was distributed to all nonpediatric IDC members of the Infectious Diseases Society of America's Emerging Infections Network in August 2003. Each member was suggested 1 of 10 treatment failure rates and asked whether he or she would accept or reject the given value. Logistic regression was used to evaluate the relationship between specific failure rates offered to respondents and their willingness to accept them using a methodology derived from contingent valuation.

RESULTS: Among the 374 respondents (response rate, 54%), the median acceptable failure rate was 6.8%. Thus, one-half of the IDCs would have found a failure rate of 6.8% to be acceptable. Seventy-five percent of IDCs would have found a failure rate of 1.6% to be acceptable, and 25% of IDCs would have found a failure rate as high as 11.9% to be acceptable.

CONCLUSIONS: The quantified acceptable failure rates, when used to interpret clinical trial or cohort study results, will help select optimal antimicrobial therapy durations for this specific condition. These findings are a critical step in the development of effective shared decision-making models.}, } @article {pmid16286918, year = {2005}, author = {Komatsu, S and Lee, CJ and Hosokawa, Y and Hamashima, T and Shirono, K and Ichikawa, D and Okabe, H and Kurioka, H and Yamagishi, H and Oka, T}, title = {A case of occult contralateral breast cancer incidentally detected by contrast-enhanced MRI; report of a case with review of literature.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {4}, pages = {341-345}, doi = {10.2325/jbcs.12.341}, pmid = {16286918}, issn = {1340-6868}, mesh = {Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Functional Laterality ; Humans ; Lymph Node Excision ; Magnetic Resonance Imaging ; Mastectomy, Segmental ; Neoplasms, Second Primary/*pathology/surgery ; Neoplasms, Unknown Primary/*pathology/surgery ; Treatment Outcome ; }, abstract = {We encountered a case of occult contralateral breast cancer, previously undetected by conventional imaging such as mammography (MMG) and ultrasonography (US), but incidentally detected by contrast-enhanced magnetic resonance imaging (CE-MRI). We present it here with a review of the literature. A 67-year-old Japanese woman was referred to our hospital in October 2000 because of a 1.5 cm right breast lump detected in a medical checkup. MMG, US and fine needle aspiration cytology revealed a cancerous lesion during the right breast. No mass lesion was palpable nor was any detected by MMG or US in the left breast. Bilateral breast CE-MRI was performed for more detailed evaluation. Consequently, an occult contralateral breast cancerous lesion was detected incidentally by CE-MRI, with the images showing rapid initial enhancement of time to signal intensity curves. Before surgery, bilateral breast lesions were diagnosed as invasive ductal carcinoma by open biopsy. She underwent bilateral breast conserving surgery with bilateral axillary lymph node dissection. The postoperative course was uneventful and no recurrence has been noted as of January 18th, 2004. CE-MRI of the contralateral breast should be of value as a routine screen in those patients with a known or suspected malignancy in one breast considering the limits of breast cancer detection by such conventional modalities as MMG and US.}, } @article {pmid16286911, year = {2005}, author = {Ohta, T and Tsujimoto, F and Nakajima, Y and Fukuda, M and Takag, M}, title = {Ultrasonographic findings of invasive lobular carcinoma differentiation of invasive lobular carcinoma from invasive ductal carcinoma by ultrasonography.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {4}, pages = {304-311}, doi = {10.2325/jbcs.12.304}, pmid = {16286911}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology ; Carcinoma, Lobular/*diagnostic imaging/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness/*diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography ; }, abstract = {BACKGROUND: Although controversy exists, invasive lobular carcinoma (ILC) differs in its high frequency of microscopically positive margins after conservative therapy compared to invasive ductal carcinoma (IDC). If ILC could be recognized by imaging modalities, it would provide important information for surgeons. We tried to confirm whether it is possible to distinguish ILC from other invasive carcinomas by ultrasonography (US).

METHODS: A total of 81 histologically confirmed cases of IDC, including 26 cases of papillotubular carcinoma, 28 cases of solid-tubular carcinoma and 27 cases of scirrhous carcinoma, as well as 24 cases of ILC were selected and retrospectively studied with regard to the features of mass lesions on US examination.

RESULTS: The sensitivities of US for papillotubular carcinoma, solid-tubular carcinoma, scirrhous carcinoma and ILC were 88.5%, 100%, 92.6% and 91.7% respectively. We could divide invasive breast cancer into two groups by US findings. One group had a low frequency of malignant findings and consisted of papillotubular and solid-tubular carcinomas, and the other group had a high frequency of malignant findings and consisted of scirrhous carcinomas and ILC. However, there were no statistical differences between papillotubular carcinoma and solid-tubular carcinoma or between scirrhous carcinoma and ILC with regard to the US findings.

CONCLUSIONS: Scirrhous carcinoma, the most common type of IDC, and ILC are difficult to distinguish by US. Therefore it is difficult to separate ILC from IDC by US.}, } @article {pmid16285589, year = {2005}, author = {Tamura, M and Yamamoto, M and Shima, K and Nakamura, T and Hirasawa, T and Takeyama, Y and Yoshida, K and Suzuki, K}, title = {[Three cases of transcatheter embolization for pulmonary arteriovenous fistula using detachable coils].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {43}, number = {10}, pages = {583-587}, pmid = {16285589}, issn = {1343-3490}, mesh = {Aged ; Arteriovenous Fistula/diagnostic imaging/*therapy ; *Embolization, Therapeutic/instrumentation ; Female ; Humans ; Middle Aged ; Pulmonary Artery/*abnormalities ; Pulmonary Veins/*abnormalities ; Radiography ; }, abstract = {We report three cases of transcatheter embolization for pulmonary arteriovenous fistula (PAVF) using Interlocking detachable coils (IDC) and detachable fibered coils (DFC), and evaluate the outcome of transcatheter embolization with reference to previous reports. The three patients were women aged 56, 70 and 71 years. They had no symptoms, but chest radiographs were abnormal. None of them had Rendu-Osler-Weber disease. The three PAVFs were of the simple type, with a single feeding vessel and a single draining vein. In case 1, the feeding vessel arose from the left A4, while the feeding vessels in case 2 and 3 arose from the left A5. In case 1, we embolized the venous sac with detachable coils because the feeding vessel was short and kinked. In case 2 and 3, we embolized the feeding vessels closer as to the neck of the venous sac using detachable coils. The three PAVFs were all successfully embolized without severe complications, and transcatheter embolization seems to be an effective therapy.}, } @article {pmid16282452, year = {2005}, author = {Narváez, CF and Angel, J and Franco, MA}, title = {Interaction of rotavirus with human myeloid dendritic cells.}, journal = {Journal of virology}, volume = {79}, number = {23}, pages = {14526-14535}, pmid = {16282452}, issn = {0022-538X}, mesh = {Cells, Cultured ; Dendritic Cells/*physiology ; Humans ; Interferon-gamma/biosynthesis ; Interleukin-10/biosynthesis ; Interleukin-12/biosynthesis ; Interleukin-4/biosynthesis ; Lymphocyte Activation ; Rotavirus/*physiology ; }, abstract = {We have previously shown that very few rotavirus (RV)-specific T cells that secrete gamma interferon circulate in recently infected and seropositive adults and children. Here, we have studied the interaction of RV with myeloid immature (IDC) and mature dendritic cells (MDC) in vitro. RV did not induce cell death of IDC or MDC and induced maturation of between 12 and 48% of IDC. Nonetheless, RV did not inhibit the maturation of IDC or change the expression of maturation markers on MDC. After treatment with RV, few IDC expressed the nonstructural viral protein NSP4. In contrast, a discrete productive viral infection was shown in MDC of a subset of volunteers, and between 3 and 46% of these cells expressed NSP4. RV-treated IDC secreted interleukin 6 (IL-6) (but not IL-1beta, IL-8, IL-10, IL-12, tumor necrosis factor alpha, or transforming growth factor beta), and MDC released IL-6 and small amounts of IL-10 and IL-12p70. The patterns of cytokines secreted by T cells stimulated by staphylococcal enterotoxin B presented by MDC infected with RV or uninfected were comparable. The frequencies and patterns of cytokines secreted by memory RV-specific T cells evidenced after stimulation of peripheral blood mononuclear cells (PBMC) with RV were similar to those evidenced after stimulation of PBMC with RV-infected MDC. Finally, IDC treated with RV strongly stimulated naive allogeneic CD4+ T cells to secrete Th1 cytokines. Thus, although RV does not seem to be a strong maturing stimulus for DC, it promotes their capacity to prime Th1 cells.}, } @article {pmid16276696, year = {2005}, author = {Gukas, ID and Jennings, BA and Mandong, BM and Igun, GO and Girling, AC and Manasseh, AN and Ugwu, BT and Leinster, SJ}, title = {Clinicopathological features and molecular markers of breast cancer in Jos, Nigeria.}, journal = {West African journal of medicine}, volume = {24}, number = {3}, pages = {209-213}, doi = {10.4314/wajm.v24i3.28220}, pmid = {16276696}, issn = {0189-160X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Black People/genetics ; Breast Neoplasms/*diagnosis/ethnology/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Neoplasm Staging ; Nigeria ; Prognosis ; }, abstract = {BACKGROUND: Several studies have suggested that breast cancer in black women is associated with aggressive features and poor survival. This study examines molecular markers along with clinical stage and pathological grade in breast cancer material from Jos, Nigeria.

STUDY DESIGN: The histological diagnoses of 178 consecutive Nigerian patients with breast cancer were retrieved from their hospital records. A subset of 36 patients was staged and their tumours typed and graded. Immunohistochemical staining of sections from paraffin wax embedded tissues from these cases for the expression of oestrogen receptor (ER), progesterone receptor (PGR), Human ERBB2 (or HER2/neu), p53 and cyclin D1 (CCND1) was carried out using the avidin biotin complex (ABC) procedure.

RESULTS: A majority of the cases were invasive ductal carcinoma (92.7%), high grade (grade 3, 70.6%) and of late clinical stage (stages III and IV, 58.3%). Only 25% and 27.8% of cases expressed ER and PGR respectively. The ERBB2 and CCND1 antigens were expressed in 25%, and 5.7% of cases respectively. The p53 protein was the most frequently expressed in this study (47.2% of cases). High grade tumours were significantly more likely to be ER and PGR negative (P = 0.006 and P = 0.002 respectively). CONLCLUSION: There is predominance of high grade, invasive ductal carcinomas which are likely to be ER and PGR negative but p53 positive. These features suggest a biologically aggressive form of breast cancer in Nigerian women with the possibility of poor response to both hormonal therapy and chemotherapy.}, } @article {pmid16275197, year = {2005}, author = {Tziakas, DN and Chalikias, GK and Papaioakeim, M and Hatzinikolaou, EI and Stakos, DA and Tentes, IK and Papanas, N and Kortsaris, A and Maltezos, E and Hatseras, DI}, title = {Comparison of levels of matrix metalloproteinase-2 and -3 in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {96}, number = {10}, pages = {1449-1451}, doi = {10.1016/j.amjcard.2005.06.096}, pmid = {16275197}, issn = {0002-9149}, mesh = {Aged ; Cardiomyopathy, Dilated/*blood/physiopathology ; Female ; Heart Failure/blood/physiopathology ; Heart Ventricles/pathology/physiopathology ; Humans ; Male ; Matrix Metalloproteinase 2/*blood ; Matrix Metalloproteinase 3/*blood ; Middle Aged ; Myocardial Ischemia/*blood/physiopathology ; Tissue Inhibitor of Metalloproteinase-1/blood ; Ventricular Remodeling/physiology ; }, abstract = {It has been reported that circulating matrix metalloproteinase (MMP) levels are upregulated in patients with chronic heart failure. However, experimental studies indicate that differences in the profiles of MMPs and tissue inhibitors of metalloproteinase (TIMPs) may exist in ischemic compared with nonischemic cardiomyopathy. This study examined whether circulating levels of MMPs and TIMP-1 are related to the pathogenesis of heart failure. Circulating levels of MMP-2, MMP-3, and TIMP-1 were assessed in 52 patients with compensated end-stage chronic heart failure, including 26 patients (mean 64 +/- 7 years; 10 men) with ischemic cardiomyopathy (IC) and 26 (mean age 66 +/- 6 years; 14 men) with idiopathic dilated cardiomyopathy (IDC). Serum MMP-2 (p <0.001) and MMP-3 (p <0.001) levels were higher in patients with IDC than in those with IC. Serum TIMP-1 levels were lower in patients with IDC (p = 0.011) than in those with IC. This study shows that in patients with compensated end-stage chronic heart failure, circulating levels of MMP-2, MMP-3, and TIMP-1 are associated with the pathogenesis of heart failure.}, } @article {pmid16264937, year = {2005}, author = {Katz, MS and Schapira, L and Harisinghani, MG and Hughes, KS}, title = {Palpable right breast mass in a pregnant woman.}, journal = {Nature clinical practice. Oncology}, volume = {2}, number = {4}, pages = {218-21; quiz 1 p following 222}, doi = {10.1038/ncponc0135}, pmid = {16264937}, issn = {1743-4254}, mesh = {Adult ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Combined Modality Therapy ; Diagnosis, Differential ; Female ; Gestational Age ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mastectomy ; Pregnancy ; Pregnancy Complications, Neoplastic/*pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: A 29-year-old female presented with a palpable right breast mass at a 12-week prenatal visit. She had no family history of breast or ovarian cancer. Ultrasound revealed a 3 cm lobulated mass, which was confirmed to be malignant by a core biopsy. Postmastectomy pathology at 15 weeks' gestation demonstrated this mass to be a stage T2N0M0 high-grade invasive ductal carcinoma with 0/20 axillary nodes involved. A staging CT scan postpartum showed an enlarged right internal mammary lymph node, confirmed by MRI as suspicious for malignancy.

INVESTIGATIONS: Physical examination, breast ultrasound, core biopsy, mastectomy, CT scan, MRI.

DIAGNOSIS: Pregnancy-associated breast carcinoma.

MANAGEMENT: Mastectomy, chemotherapy and radiotherapy.}, } @article {pmid16261396, year = {2006}, author = {Marshall, C and Blackburn, E and Clark, M and Humphreys, S and Gullick, WJ}, title = {Neuregulins 1-4 are expressed in the cytoplasm or nuclei of ductal carcinoma (in situ) of the human breast.}, journal = {Breast cancer research and treatment}, volume = {96}, number = {2}, pages = {163-168}, doi = {10.1007/s10549-005-9073-z}, pmid = {16261396}, issn = {0167-6806}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Female ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Neuregulins/immunology/*metabolism ; }, abstract = {A new family of epidermal growth factor-like proteins, the Neuregulins (NRGs), have recently been identified and are expressed in a range of normal tissues and in some forms of cancer including breast cancer. In this study we examined using immunohistochemical staining expression of NRG1alpha, NRG1beta, NRG2alpha, NRG2beta, NRG3 and NRG4 in sixty cases of pre-invasive ductal carcinoma in situ of the breast representing different degrees of differentiation. Each protein was expressed in a high proportion of these cases showing a predominantly homogenous cytoplasmic staining pattern. Nuclear expression of NRG1alpha, NRG1beta, and NRG3 was however also observed in a significant fraction of cases. High levels of expression of NRG2beta and NRG4 were associated with high-grade tumours (p< or =0.005), NRG2beta staining was associated with tumour size >25 mm (p=0.005) while NRG3 nuclear staining was present more often in low-grade tumours (p=0.039). This data demonstrates that each member of the NRG family of ligands is present in pre-invasive ductal breast cancer and that they may be involved in regulating cell behaviour. The significance of intranuclear expression remains to be determined but suggests a novel mechanism of action for some of these proteins.}, } @article {pmid16258765, year = {2006}, author = {Tatsumi, M and Cohade, C and Mourtzikos, KA and Fishman, EK and Wahl, RL}, title = {Initial experience with FDG-PET/CT in the evaluation of breast cancer.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {33}, number = {3}, pages = {254-262}, pmid = {16258765}, issn = {1619-7070}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Middle Aged ; Pilot Projects ; Positron-Emission Tomography/*methods ; Radiopharmaceuticals ; Reproducibility of Results ; Sensitivity and Specificity ; *Subtraction Technique ; Tomography, X-Ray Computed/*methods ; }, abstract = {PURPOSE: We retrospectively reviewed FDG-PET/CT images in patients with breast cancer to determine whether PET/CT improved the level of diagnostic confidence as compared with PET and to compare PET/CT and CT findings at the location of suspected malignancies.

METHODS: The study included 75 patients with known breast cancer. The initial PET/CT study for each patient was retrospectively reviewed to determine whether improved diagnostic confidence (IDC) regarding lesion localization and characterization was observed with PET/CT as compared with PET alone. PET/CT and CT findings were compared regarding lesion characterization and staging in 69 of the 75 patients, and in the case of discordant findings, comparison with histological or informative follow-up results was also performed.

RESULTS: Fifty of the 75 patients exhibited increased FDG uptake in a total of 95 regions. In the comparison of PET/CT and PET, PET/CT resulted in IDC in 30 (60%) of these 50 patients and in 52 (55%) of the 95 regions. In the comparison between PET/CT and CT in 69 patients, PET/CT demonstrated a significantly better accuracy than CT (P<0.05). PET/CT showed definitely positive findings in 60 regions with malignancies, among which CT exhibited positive findings in 43 (72%). PET/CT and CT accurately staged 59 (86%) and 53 (77%) of the 69 patients, respectively.

CONCLUSIONS: PET/CT added incremental diagnostic confidence to PET in more than 50% of patients and regions with increased FDG uptake. PET/CT accurately detected more regions with malignancies than did CT. This initial evaluation suggests that PET/CT is preferable to PET or CT in the diagnosis of breast cancer.}, } @article {pmid16258702, year = {2005}, author = {Nagi, C and Guttman, M and Jaffer, S and Qiao, R and Keren, R and Triana, A and Li, M and Godbold, J and Bleiweiss, IJ and Hazan, RB}, title = {N-cadherin expression in breast cancer: correlation with an aggressive histologic variant--invasive micropapillary carcinoma.}, journal = {Breast cancer research and treatment}, volume = {94}, number = {3}, pages = {225-235}, doi = {10.1007/s10549-005-7727-5}, pmid = {16258702}, issn = {0167-6806}, support = {5 R24 CA 88282-04/CA/NCI NIH HHS/United States ; R01 CA90872/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, CD ; Breast Neoplasms/*pathology ; Cadherins/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*pathology ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; *Neoplasm Invasiveness ; Phenotype ; Up-Regulation ; }, abstract = {Upregulation of N-cadherin in epithelial tumor cells has been shown to contribute to the invasive/metastatic phenotype. It remains however to be determined whether N-cadherin is increased in human breast cancers with enhanced malignant potential. We examined a large number of invasive breast cancer specimens (n = 114) for N- and E-cadherin. These specimens compared invasive duct carcinomas (IDCs) of varying histologic grades with an aggressive subtype, invasive micropapillary carcinoma of the breast (MPAP), which has a high propensity for lymphatic invasion and lymph node metastasis. Staining scores for N- and E-cadherin were compared between non-MPAP and MPAP IDCs, and between the invasive and ductal carcinoma in situ (DCIS) of each IDC using statistical analysis. We found that N-cadherin was expressed in 76% of MPAP and 52% of non-MPAP carcinomas, and E-cadherin in 57% of MPAP and 36% of non-MPAP tumors. More MPAP (25%) compared to non-MPAP (5%) tumors expressed both cadherins. Of the two cadherins, N-cadherin was significantly associated with MPAP tumors (p = 0.033) compared to E-cad (p = 0.171). Moreover, in the majority of tumors that were positive for N-cadherin, the staining scores were increased in the IDC relative to intraductal components, and this effect was more dramatic in the MPAP carcinomas. This difference for N-cadherin was greater than the corresponding difference for E-cadherin in the MPAP group (p = 0.005), whereas such changes were not significant in the non-MPAP group (p = 0.10). Thus, N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression.}, } @article {pmid16257133, year = {2006}, author = {Zhang, Y and Ma, QY and Dang, CX and Moureau-Zabotto, M and Chen, WK}, title = {Quantitative molecular diagnosis of axillary drainage fluid for prediction of locoregional failure in patients with one to three positive axillary nodes after mastectomy without adjuvant radiotherapy.}, journal = {International journal of radiation oncology, biology, physics}, volume = {64}, number = {2}, pages = {505-511}, doi = {10.1016/j.ijrobp.2005.07.984}, pmid = {16257133}, issn = {0360-3016}, mesh = {Adult ; Analysis of Variance ; Axilla ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/mortality/*pathology/surgery ; Carcinoembryonic Antigen/*analysis ; Carcinoma, Ductal, Breast/mortality/*secondary/surgery ; Female ; Humans ; Keratins/*analysis ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Models, Biological ; Neoplasm Recurrence, Local/metabolism/pathology ; Neoplasm, Residual ; Radiotherapy, Adjuvant ; Reverse Transcriptase Polymerase Chain Reaction/*methods/standards ; Sensitivity and Specificity ; }, abstract = {PURPOSE: A quantitative multiple-marker reverse transcriptase (RT)-polymerase chain reaction (PCR) assay for sensitive detection of cancer cells in axillary drainage fluid was developed to examine whether the presence of cancer cells in axillary drainage fluid can be used as a predictor of locoregional recurrence (LRR) in patients with breast cancer who had T1/2 primary tumors and one to three positive axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy.

METHODS AND MATERIALS: Axillary drainage fluid was collected from 126 patients with invasive ductal carcinoma of the breast who were treated with modified radical mastectomy and were found to have one to three positive axillary nodes. Cancer cells in axillary drainage fluid were detected by RT-PCR assay using primers specific for carcinoembryonic antigen (CEA) and cytokeratin-19 (CK-19) together with numerous clinicopathologic and treatment-related factors and were analyzed for their impact on LRR.

RESULTS: A total of 38 patients suffered LRR during follow-up and the multimarker RT-PCR assays for CEA and CK-19 in the axillary drainage fluid both were positive in 34 patients (27.0%), of which 29 patients had LRR. In univariate analysis, the 5-year LRR-free survival showed higher rates in patients with PCR-negative findings in axillary drainage fluid (p<0.0001), age>or=40 years old (p<0.0001), tumor size<2.5 cm (p<0.0001), negative lymph-vascular space invasion (p=0.026), and T1 status (<0.0001); in multivariate analysis, PCR-positive findings together with age and tumor size were found to be independent predictors of LRR (all p<0.05).

CONCLUSION: Multiplex RT-PCR assay for CEA and CK-19 was highly sensitive for detection and might be useful for prediction of LRR in such subgroup breast cancer patients.}, } @article {pmid16246429, year = {2006}, author = {Leong, PP and Mohammad, R and Ibrahim, N and Ithnin, H and Abdullah, M and Davis, WC and Seow, HF}, title = {Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast.}, journal = {Immunology letters}, volume = {102}, number = {2}, pages = {229-236}, doi = {10.1016/j.imlet.2005.09.006}, pmid = {16246429}, issn = {0165-2478}, mesh = {Adult ; Breast Neoplasms/*immunology ; CD28 Antigens/analysis ; CD4-CD8 Ratio ; Carcinoma, Ductal/*immunology ; Estrogen Receptor alpha/analysis ; Female ; Forkhead Transcription Factors/analysis ; Humans ; *Immunophenotyping ; Lymphocytes, Tumor-Infiltrating/*classification/immunology ; Middle Aged ; Receptors, Interleukin-2/analysis ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Dysfunction of the host immune system in cancer patients can be due to a number of reasons including suppression of tumour associated antigen reactive lymphocytes by regulatory T (Treg) cells. In this study, we used flow cytometry to determine the phenotype and relative abundance of the tumour infiltrating lymphocytes (TILs) from 47 enzymatically dissociated tumour specimens from patients with infiltrating ductal carcinoma (IDC) of the breast. The expression of both effector and regulatory markers on the TILs were determined by using a panel of monoclonal antibodies. Analysis revealed CD8(+) T cells (23.4+/-2.1%) were predominant in TILs, followed by CD4(+) T cells (12.6+/-1.7%) and CD56(+) natural killer cells (6.4+/-0.7%). The CD4(+)/CD8(+) ratio was 0.8+/-0.9%. Of the CD8(+) cells, there was a higher number (68.4+/-3.5%) that expressed the effector phenotype, namely, CD8(+)CD28(+) and about 46% of this subset expressed the activation marker, CD25. Thus, a lower number of infiltrating CD8(+) T cells (31.6+/-2.8%) expressed the marker for the suppressor phenotype, CD8(+)CD28(-). Of the CD4(+) T cells, 59.6+/-3.9% expressed the marker for the regulatory phenotype, CD4(+)CD25(+). About 43.6+/-3.8% CD4(+)CD25(+) subset co-expressed both the CD152 and FOXP3, the Treg-associated molecules. A positive correlation was found between the presence of CD4(+)CD25(+) subset and age (> or =50 years old) (r=0.51; p=0.045). However, no significant correlation between tumour stage and CD4(+)CD25(+) T cells was found. In addition, we also found that the CD4(+)CD25(-) subset correlated with the expression of the nuclear oestrogen receptor (ER)-alpha in the tumour cells (r=0.45; p=0.040). In conclusion, we detected the presence of cells expressing the markers for Tregs (CD4(+)CD25(+)) and suppressor (CD8(+)CD28(-)) in the tumour microenvironment. This is the first report of the relative abundance of Treg co-expressing CD152 and FOXP3 in breast carcinoma.}, } @article {pmid16244250, year = {2005}, author = {Espinosa, LA and Daniel, BL and Vidarsson, L and Zakhour, M and Ikeda, DM and Herfkens, RJ}, title = {The lactating breast: contrast-enhanced MR imaging of normal tissue and cancer.}, journal = {Radiology}, volume = {237}, number = {2}, pages = {429-436}, doi = {10.1148/radiol.2372040837}, pmid = {16244250}, issn = {0033-8419}, mesh = {Adult ; Breast/*anatomy & histology/pathology ; Breast Neoplasms/*pathology ; Contrast Media/pharmacokinetics ; Female ; Gadolinium DTPA/pharmacokinetics ; Humans ; *Lactation ; Least-Squares Analysis ; Magnetic Resonance Imaging/*methods ; Retrospective Studies ; Statistics, Nonparametric ; }, abstract = {PURPOSE: To retrospectively describe the magnetic resonance (MR) imaging characteristics of normal breast tissue and breast cancer in the setting of lactation.

MATERIALS AND METHODS: The HIPAA-compliant study was exempt from institutional approval, and informed consent was not required. Unilateral MR imaging of 10 breasts was performed in seven lactating patients aged 27-42 years. For the three patients in whom both breasts were imaged, each breast was imaged on a separate day. Nonenhanced T1-weighted and fat-saturated T2-weighted images and contrast material-enhanced dynamic three-dimensional (3D) T1-weighted spiral gradient-echo images interleaved with T1-weighted high-spatial-resolution 3D gradient-echo images (2.0 x 1.0 x 0.4-mm voxels) were obtained. Three readers in consensus assessed the glandular density, T2-weighted signal intensity, milk duct appearance, and contrast enhancement in normal and tumor-containing breast regions. The pharmacokinetic contrast enhancement parameters of tumors were compared with those of normal tissue by using Student t and Mann-Whitney tests.

RESULTS: MR findings of normal breast tissue in the seven women included increased glandular density in six women, high T2-weighted signal intensity in six, dilated central ducts in seven, and rapid initial glandular contrast enhancement in seven. MR findings of invasive ductal carcinoma in five women, compared with findings of the normal glandular tissue, included lower T2-weighted signal intensity in five women, more avid and rapid contrast enhancement in five, and early contrast enhancement washout in four. One minute after contrast agent injection, tumor signal intensity increased significantly more than normal lactating tissue signal intensity (153% vs 60% from baseline, P = .016). The median two-compartment model K(21) exchange rate in the tumors, 0.078 sec(-1), was significantly faster than the K(21) exchange rate in normal tissue, 0.011 sec(-1) (P = .03).

CONCLUSION: Normal lactating glands have increased density, high T2-weighted signal intensity, and rapid moderate contrast enhancement. Breast cancers are visible during lactation owing to their lower signal intensity and more intense initial contrast enhancement with early washout compared with normal breast tissue.}, } @article {pmid16236472, year = {2006}, author = {Cárdaba, B and del Pozo, V and Gallardo, S and Palomino, P and Posada, M and Lahoz, C}, title = {Genetic approaches in the understanding of Toxic Oil Syndrome.}, journal = {Toxicology letters}, volume = {161}, number = {1}, pages = {83-88}, doi = {10.1016/j.toxlet.2005.09.027}, pmid = {16236472}, issn = {0378-4274}, mesh = {Adult ; Case-Control Studies ; Chromosomes, Human, Pair 6/genetics ; Eosinophilia/etiology ; Fatty Acids, Monounsaturated ; Female ; Gene Frequency/genetics ; Genetic Markers/genetics ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Liver Diseases/etiology ; Logistic Models ; Lung Diseases/etiology ; Male ; Microsatellite Repeats/genetics ; Odds Ratio ; Plant Oils/administration & dosage/*poisoning ; Rapeseed Oil ; Scleroderma, Systemic/etiology ; Sex Factors ; Spain ; Syndrome ; }, abstract = {The Toxic Oil Syndrome (TOS) is a multisystemic disease that occurred in Spain in 1981 due to the ingestion of rapeseed oil denatured with 2% aniline. Female prevalence and the different clinical evolution even inside the same family (similar exposition), pointed to genetic implications. Furthermore, HLA-DR2 was increased in patients dead because of TOS. Th2 activation and eosinophilia implicated immunological mechanisms. For those reasons we firstly decided, to do a genome-wide search by linkage mapping set along the chromosome 6 (where HLA loci are located), to identify loci associated to the TOS development. The design was case-control-matched (n = 328). By this procedure, microsatellite (near to HLA) was related with the patients. After fine-mapping around this marker, we defined four more closely related to TOS-, , and . Secondly, we analysed in 420 patients, the association of these four markers with 14 TOS clinical phenotypes. We demonstrated that alveolar infiltration, liver disease and scleroderma are clearly associated with . As conclusion, we have identified in chromosome 6, a region where are located some genes related with autoimmune diseases, associated with certain TOS phenotypes, pointing out the possible role of autoimmune reactions in the pathogenesis of the disease.}, } @article {pmid16236180, year = {2005}, author = {Saxena, S and Rekhi, B and Bansal, A and Bagga, A and Chintamani, and Murthy, NS}, title = {Clinico-morphological patterns of breast cancer including family history in a New Delhi hospital, India--a cross-sectional study.}, journal = {World journal of surgical oncology}, volume = {3}, number = {}, pages = {67}, pmid = {16236180}, issn = {1477-7819}, abstract = {BACKGROUND: Breast cancer is the second most common malignancy among women, next to cervix cancer. Understanding its pathogenesis, morphological features and various risk-factors, including family history holds a great promise for the treatment, early detection and prevention of this cancer.

PATIENTS AND METHODS: In an attempt to evaluate the clinico-morphological patterns of breast cancer patients, including their family history of breast and/or other cancers, a detailed analysis of 569 breast cancer cases diagnosed during the years 1989-2003 was carried out. Mean and standard deviation and Odds ratios along with 95% confidence intervals were estimated. Chi2/Fisher's exact test were employed to test for proportions.

RESULTS: Mean age of the patient at presentation was 47.8 years, ranging from 13-82 years. Among the various histo-morphological types, Infiltrating duct carcinoma (IDC) was found to be commonest type i.e. in 502 cases (88.2%), followed by infiltrating lobular carcinoma (ILC) in 21 cases (3.7%) and other types forming 9(1%). Out of 369 cases where TNM staging was available, stage IIIB (35.2%) was the commonest. Lymph node positivity was observed in 296 cases (80.2%). Out of 226 cases evaluated for presence of family history, 47 cases (20.7%) revealed positive family history of cancer, among which breast or ovarian cancer were the commonest type (72.0%). Patients below 45 years of age had more frequent occurrence of family history as compared to above 45 years. Amongst familial cases, Infiltrating duct carcinoma was the commonest form accounting for 68.8% cases while ILC was found to be in a higher proportion (12.5%) as compared to non- familial cases (5.4%).

CONCLUSION: Among the various determining factors for development of breast cancer and for its early detection, family history of cancer forms one of the major risk factor. It is important to take an appropriate history for eliciting information pertaining to occurrence of cancers amongst the patients' relatives there by identifying the high risk group. Educating the population about the risk factors would be helpful in early detection of breast cancer.}, } @article {pmid16230949, year = {2005}, author = {Giusiano, S and Andrac-Meyer, L and Meunier-Carpentier, S and Xerri, L and Boubli, L and Taranger-Charpin, C}, title = {[A tumor-like lymphocytis mastitis].}, journal = {Annales de pathologie}, volume = {25}, number = {3}, pages = {231-234}, doi = {10.1016/s0242-6498(05)80114-2}, pmid = {16230949}, issn = {0242-6498}, mesh = {Adult ; Breast Neoplasms/pathology ; Diagnosis, Differential ; Female ; Humans ; Inflammation ; Lymphocytes/*pathology ; Mastitis/*pathology/surgery ; Necrosis ; }, abstract = {A 44-year-old woman presenting with an inflammatory and palpable firm breast lump underwent surgical excision. Intraoperative frozen section analysis showed an extensive lesion consisting of ducts with intraluminal "necrosis". In addition, a very dense stromal inflammation was observed around these ducts, suggesting an invasive ductal carcinoma with predominant intraductal proliferation. However, on paraffin sections, epithelial cells close to the lymphocytic infiltrate were rare, subatrophic, without any neoplastic feature. The density and architecture of the lymphocytic infiltrate mimicked a breast lymphoma. However, immunochemistry and molecular biology investigation favored the diagnosis of a tumor-like lymphocytic mastitis. Although extremely rare, this particular form of lymphocytic mastitis, a diagnostic pitfall particularly during peroperative examination, should be recognized by pathologists.}, } @article {pmid16225776, year = {2004}, author = {Liu, W and Li, W and Sun, N}, title = {Association of HLA-DQ with idiopathic dilated cardiomyopathy in a northern Chinese Han population.}, journal = {Cellular & molecular immunology}, volume = {1}, number = {4}, pages = {311-314}, pmid = {16225776}, issn = {1672-7681}, mesh = {Adolescent ; Adult ; Aged ; Asian People/*genetics ; Autoimmune Diseases/genetics ; Cardiomyopathy, Dilated/*genetics ; Case-Control Studies ; China ; Ethnicity/*genetics ; Female ; Gene Frequency ; *Genes, MHC Class II ; Genotype ; HLA-DQ Antigens/*genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Humans ; Male ; Middle Aged ; }, abstract = {Autoimmune mechanisms are likely involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) and components of MHC may serve as markers for the propensity to develop immune-mediated myocardial damage. This study was conducted to investigate the possible association between HLA-DQA1, -DQB1 alleles and IDC in Han population from northern China by using PCR-based sequence-specific primer (PCR-SSP) technique for HLA genotyping. Among 68 unrelated IDC patients, 4 probands of IDC pedigrees and 100 healthy controls, we found that the alleles of HLA-DQA1*0501 and HLA-DQB1*0303 conferred susceptibility to IDC while HLA-DQA1*0201 and HLA-DQB1*0502, *0504 alleles were in negative association with IDC. The serine at position 57 (SER57) in the exon of HLA-DQB1*0502 and *0504 was confirmed in our experiment as a marker for resistance to IDC. The results suggest that HLA-DQ polymorphism may be involved in the pathogenesis of IDC.}, } @article {pmid16224211, year = {2005}, author = {Agarwal, B and Saxena, R and Morimiya, A and Mehrotra, S and Badve, S}, title = {Lymphangiogenesis does not occur in breast cancer.}, journal = {The American journal of surgical pathology}, volume = {29}, number = {11}, pages = {1449-1455}, doi = {10.1097/01.pas.0000174269.99459.9d}, pmid = {16224211}, issn = {0147-5185}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal, Murine-Derived ; Biomarkers ; Biomarkers, Tumor ; Breast/pathology/*physiology ; Breast Neoplasms/pathology/*physiopathology ; Carcinoma, Ductal, Breast/pathology/physiopathology ; Carcinoma, Intraductal, Noninfiltrating/pathology/*physiopathology ; Carcinoma, Lobular/pathology/*physiopathology ; Female ; Homeodomain Proteins/immunology ; Humans ; Lymphangiogenesis/*physiology ; Lymphatic Metastasis ; Membrane Glycoproteins/immunology ; Middle Aged ; Proliferating Cell Nuclear Antigen/immunology ; Tumor Suppressor Proteins ; }, abstract = {Breast cancer metastasis predominantly occurs via lymphatic vessels. However, the study of lymphatic vessels and lymphangiogenesis has been hampered by lack of specific markers. Recently, antibodies directed against M2A (D2-40), Podoplanin, and Prox-1 that specifically mark lymphatic vessels in paraffin-embedded sections have become available. These were used to study lymphangiogenesis in archival paraffin sections of normal breast (n = 23), fibrocystic disease (n = 7), ductal carcinoma in situ (n = 32), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 5). In addition, endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and proliferating cell nuclear antigen (PCNA). Expression of D2-40, Prox-1, and Podoplanin was seen in lymphatic vessels but not in blood vessels. Lymphatic vessels were seen in the peritumoral area and as "entrapped" intratumoral vessels adjacent to preexisting normal lobules and ducts. Unlike angiogenesis, there was no increase of lymphatic vessel density in association with neoplastic transformation. On the contrary, a marked reduction in intratumoral lymphatic vessel density was seen in comparison to normal breast tissue, fibrocystic disease, and ductal carcinoma in situ (P = 0.0001). There was an increase in peritumoral lymphatic vessel density as compared with normal breast (P = 0.0001). However, the endothelial cells in the "entrapped" or the peritumoral lymphatic vessels did not show any expression of PCNA indicating minimal or no proliferative activity. This was in contrast to the strong expression seen in adjacent tumor cells and blood vessel endothelial cells. Thus, lymphangiogenesis was not evident when studied by lymphatic vessel density or by lymph vessel endothelial proliferation.}, } @article {pmid16216748, year = {2005}, author = {Connors, AM and Svensson, WE and Sinnett, HD and Shousha, S}, title = {Invasive ductal carcinoma of the breast with large central acellular zones (ring carcinoma): imaging and clinical findings in eight cases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {14}, number = {5}, pages = {419-424}, doi = {10.1016/j.breast.2004.10.006}, pmid = {16216748}, issn = {0960-9776}, mesh = {Aged ; Breast Neoplasms/diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: To review the mammographic and ultrasound appearances in patients who have invasive ductal carcinoma with a central acellular zone (ring carcinoma), as this feature has been reported to be associated with a poorer outcome.

MATERIALS: Eight patients were identified with ring carcinomas. Two breast radiologists reviewed their mammograms and ultrasound images. Patient records were reviewed to assess outcome.

RESULTS: All patients had lesions deep within the breast, adjacent to the chest wall, five lesions were incompletely visualised on mammography. The appearance was of a circumscribed or obscured mass, without microcalcification. Five patients had ultrasound demonstrating a solid well-circumscribed hypoechoic microlobulated lesion.

CONCLUSION: In our series of patients who have a ring carcinoma of the breast, mammographic and ultrasound appearances were similar in all cases and lacked the typical features of malignancy.}, } @article {pmid16212073, year = {2005}, author = {Zecchin, M and Di Lenarda, A and Gregori, D and Moretti, M and Driussi, M and Aleksova, A and Chersevani, D and Sabbadini, G and Sinagra, G}, title = {Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.}, journal = {Italian heart journal : official journal of the Italian Federation of Cardiology}, volume = {6}, number = {9}, pages = {721-727}, pmid = {16212073}, issn = {1129-471X}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*diagnosis/mortality/physiopathology ; Echocardiography ; Electrocardiography, Ambulatory ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Stroke Volume ; Survival Analysis ; Tachycardia, Ventricular/complications/*diagnosis/mortality/physiopathology ; Ventricular Dysfunction, Left/diagnosis ; }, abstract = {BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain.

METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months).

RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment.

CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.}, } @article {pmid16211123, year = {2005}, author = {Brooksbank, R and Woodiwiss, A and Sliwa, K and Deftereos, D and Essop, MR and Sareli, P and Norton, GR}, title = {Sustained white cell cytokine activation in idiopathic dilated cardiomyopathy despite haemodynamic improvement with medical therapy.}, journal = {Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners}, volume = {16}, number = {4}, pages = {200-204}, pmid = {16211123}, mesh = {Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Cardiomyopathy, Dilated/blood/drug therapy/*physiopathology ; Cytokines/*blood ; Female ; Hemodynamics ; Humans ; Leukocytes/*physiology ; Losartan/therapeutic use ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/analysis ; Ventricular Function, Left/drug effects ; }, abstract = {Cytokine production in idiopathic dilated cardiomyopathy (IDC) may depend on neurohumoral stimulation, haemodynamic impairment or auto-antibody production. We aimed to ascertain the impact of haemodynamic improvements with standard medical therapy and neurohumoral blockade on white cell tumour necrosis factor- alpha (TNF-alpha) production in patients with IDC. Twenty-seven patients with IDC and NYHA class I to IV heart failure but without evidence of oedema, reduced peripheral perfusion, or elevated plasma endotoxin concentrations were evaluated for indicators of cytokine activation. Plasma TNF-alpha concentrations were raised (p < 0.001) in patients prior to commencement of medical therapy as compared to controls (n = 27). In addition, endotoxin-free cultured whole blood TNF-alpha production was enhanced (p < 0.02) in the patients. Although plasma TNF-alpha tended to decrease, excessive whole blood TNF-alpha production remained unaltered following marked improvements in haemodynamics and functional class (increase in absolute left ventricular ejection fraction = 8.7 +/- 2.6%, p < 0.01, 37% in NYHA functional class I after therapy) with six to 12 months of medical therapy (diuretic, angiotensin converting enzyme inhibitor and beta-blocker). Against a role for neurohumoral substances in promoting excessive white cell TNF-alpha synthesis the angiotensin II receptor antagonist, losartan, failed to modulate white cell TNF- alpha production in patients with IDC. We concluded that white cell TNF-alpha overproduction is sustained in patients with IDC despite haemodynamic improvement with standard medical therapy and blockade of angiotensin II receptors. These data suggest that mechanisms other than haemodynamic impairment and neurohumoral activation contribute to excess white cell TNF-alpha production in IDC.}, } @article {pmid16207355, year = {2005}, author = {Huang, S and Li, Y and Chen, Y and Podsypanina, K and Chamorro, M and Olshen, AB and Desai, KV and Tann, A and Petersen, D and Green, JE and Varmus, HE}, title = {Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice.}, journal = {Genome biology}, volume = {6}, number = {10}, pages = {R84}, pmid = {16207355}, issn = {1474-760X}, support = {P01 CA094060/CA/NCI NIH HHS/United States ; P01 CA94060-02/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm/genetics ; Genotype ; Hyperplasia ; Mammary Glands, Animal/cytology/pathology ; Mammary Neoplasms, Animal/*genetics ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Mice, Transgenic ; Wnt1 Protein/*genetics ; }, abstract = {BACKGROUND: In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development.

RESULTS: We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV-Wnt-1 transgenic mice, and 12 mammary tumors from MMTV-Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes.

CONCLUSION: We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression.}, } @article {pmid16198508, year = {2005}, author = {Vicini, F and Winter, K and Straube, W and Wong, J and Pass, H and Rabinovitch, R and Chafe, S and Arthur, D and Petersen, I and McCormick, B}, title = {A phase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319.}, journal = {International journal of radiation oncology, biology, physics}, volume = {63}, number = {5}, pages = {1531-1537}, doi = {10.1016/j.ijrobp.2005.06.024}, pmid = {16198508}, issn = {0360-3016}, support = {U24CA81647/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Combined Modality Therapy ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Prospective Studies ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted/*methods ; Radiotherapy, Conformal/*methods ; Reproducibility of Results ; }, abstract = {BACKGROUND: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken.

METHODS AND MATERIALS: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between > or = 95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value.

RESULTS: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations.

CONCLUSION: Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria.}, } @article {pmid16196516, year = {2005}, author = {Kim, MJ and Gong, G and Joo, HJ and Ahn, SH and Ro, JY}, title = {Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component.}, journal = {Archives of pathology & laboratory medicine}, volume = {129}, number = {10}, pages = {1277-1282}, doi = {10.5858/2005-129-1277-IACCOI}, pmid = {16196516}, issn = {1543-2165}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary ; Carcinoma, Papillary/chemistry/mortality/*secondary ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Survival Rate ; Tissue Array Analysis/methods ; }, abstract = {CONTEXT: A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described.

OBJECTIVE: We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC).

DESIGN: We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components.

RESULTS: Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit.

CONCLUSIONS: Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected.}, } @article {pmid16195769, year = {2005}, author = {Behjati, F and Atri, M and Najmabadi, H and Nouri, K and Zamani, M and Mehdipour, P}, title = {Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among Iranian women: an interphase FISH analysis.}, journal = {Pathology oncology research : POR}, volume = {11}, number = {3}, pages = {157-163}, pmid = {16195769}, issn = {1219-4956}, mesh = {Aneuploidy ; Biomarkers/analysis ; Breast Neoplasms/*genetics/mortality/pathology/surgery ; Carcinoma, Ductal/*genetics/mortality/pathology/surgery ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Diploidy ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Iran ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients' age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.}, } @article {pmid16187283, year = {2006}, author = {Zafrakas, M and Chorovicer, M and Klaman, I and Kristiansen, G and Wild, PJ and Heindrichs, U and Knüchel, R and Dahl, E}, title = {Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue.}, journal = {International journal of cancer}, volume = {118}, number = {6}, pages = {1453-1459}, doi = {10.1002/ijc.21517}, pmid = {16187283}, issn = {0020-7136}, mesh = {Breast/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cell Line ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization/methods ; Protein Subunits/*genetics ; RNA, Messenger/genetics/metabolism ; Receptors, GABA-A/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The GABRP gene has been previously identified by in silico analysis of four million ESTs as a candidate gene differentially expressed in breast cancer. GABRP is located on chromosome 5q34 and it encodes the pi-subunit of the gamma-aminobutyric acid (GABA) receptor, a transmembrane protein expressed in the brain and several nonneuronal tissues. Using cDNA dot blot hybridisation (cancer profiling array), quantitative RT-PCR and non-radioisotopic in situ hybridisation (ISH), we have analysed GABRP expression in breast cancer and normal breast tissues as well as in nontumorigenic and tumorigenic breast cell lines. Analysis of the cancer profiling array revealed a more than 2-fold downregulation of GABRP (p < 0.001) in 76% of primary breast carcinomas (n = 50) compared to corresponding normal tissues. Quantitative RT-PCR in a panel of 23 normal human tissues showed that the GABRP expression level was most abundant in the normal breast tissues compared to other human tissues. GABRP downregulation in breast cancer was confirmed by quantitative RT-PCR in cryopreserved breast tumour and normal breast tissue specimens (n = 22), in archival formalin-fixed, paraffin-embedded tissue specimens (n = 32), as well as in breast cancer cell lines (n = 8). Furthermore, a significant downregulation of GABRP was noted in large (pT3-pT4) (p = 0.044) primary breast tumours. Non-radioisotopic ISH showed strong GABRP expression in normal epithelial and benign papilloma breast cells, but no signal could be detected in invasive ductal carcinoma. Altogether, these data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer.}, } @article {pmid16187230, year = {2005}, author = {Gao, RJ and Bao, HZ and Yang, Q and Cong, Q and Song, JN and Wang, L}, title = {The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters.}, journal = {Breast cancer research and treatment}, volume = {93}, number = {2}, pages = {111-115}, doi = {10.1007/s10549-005-4321-9}, pmid = {16187230}, issn = {0167-6806}, mesh = {Antibodies, Neoplasm/*blood ; Biomarkers, Tumor/analysis/*blood ; Breast Neoplasms/*blood/metabolism/pathology ; Carcinoma, Ductal/*blood/metabolism/pathology ; China ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis/*immunology ; }, abstract = {Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.}, } @article {pmid16184928, year = {2005}, author = {Rai, Y and Ando, M and Sagara, Y and Takahama, T and Matsuyama, Y and Ooi, Y and Sagara, Y}, title = {[Neoadjuvant endocrine therapy with anastrozole significantly downstaged an elderly breast cancer woman with locally-advanced breast cancer which became operable].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {32}, number = {9}, pages = {1301-1305}, pmid = {16184928}, issn = {0385-0684}, mesh = {Aged ; Anastrozole ; Antineoplastic Agents, Hormonal/*therapeutic use ; Bone Neoplasms/secondary ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; *Mastectomy ; Neoadjuvant Therapy ; Nitriles/*therapeutic use ; Postmenopause ; Preoperative Care ; Sternum ; Triazoles/*therapeutic use ; }, abstract = {A 73-year-old postmenopausal woman had a 13 cm-sized huge tumor in her left breast with an extensive purple skin color change. She had sternal destruction, axillary and supraclavicular lymph node metastases (T4bN3M1, Stage IV). Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+++, PgR+++). She was treated with 1 mg per day of anastrozole. The tumor decreased in size gradually and became operable after 7.5 months of the anastrozole monotherapy. She underwent mastectomy and axillary node clearance. The resected specimen showed a 3.5 cm sized tumor with significant fibrosis and scanty viable tumor cells. We concluded that neoadjuvant therapy with anastrozole is a good choice for receptor-positive postmenopausal breast cancer, especially for elderly or poor risk women.}, } @article {pmid16183152, year = {2006}, author = {Nanas, JN and Tsagalou, EP and Nanas, SN and Terrovitis, JV and Tsolakis, EJ and Toumanidis, S and Papazoglou, PD and Alexopoulos, GP and Kanakakis, J and Anastasiou-Nana, MI}, title = {Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy.}, journal = {International journal of cardiology}, volume = {108}, number = {2}, pages = {237-243}, doi = {10.1016/j.ijcard.2005.05.010}, pmid = {16183152}, issn = {0167-5273}, mesh = {Administration, Oral ; Adult ; Aged ; Amiodarone/*administration & dosage ; Cardiomyopathy, Dilated/complications/physiopathology ; Cardiovascular Agents/*administration & dosage ; Dobutamine/*administration & dosage ; Female ; Heart Failure/*drug therapy/etiology/physiopathology ; Hemodynamics/drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Prospective Studies ; Stroke Volume/drug effects ; Ventricular Remodeling/*drug effects ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF).

METHODS: This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up.

RESULTS: A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006).

CONCLUSIONS: In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.}, } @article {pmid16180213, year = {2005}, author = {Agarwal, A and Heron, DE and Sumkin, J and Falk, J}, title = {Contralateral uptake and metastases in sentinel lymph node mapping for recurrent breast cancer.}, journal = {Journal of surgical oncology}, volume = {92}, number = {1}, pages = {4-8}, doi = {10.1002/jso.20282}, pmid = {16180213}, issn = {0022-4790}, mesh = {Adult ; Axilla ; Breast Neoplasms/diagnostic imaging/*pathology/surgery ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/*diagnostic imaging ; Neoplasm Recurrence, Local/*diagnosis ; Neoplasm Staging/*methods ; Radionuclide Imaging ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND AND OBJECTIVES: Sentinel lymph node mapping as a constitutive component in the staging process for invasive breast cancer continues to gain acceptance. We have identified two patients with recurrent invasive breast cancer in whom contralateral sentinel lymph node uptake and metastases, respectively, were detected. Such findings have not been previously reported in our review of the medical literature between 1966 and October 2004.

METHODS: Sentinel lymph node mapping was performed on two patients with recurrent invasive breast cancer at our institution. At the time of their index diagnosis, both had received breast conserving surgery and an axillary lymph node dissection with post-operative radiotherapy (RT). All lymph nodes and margins of resection were without tumor. Both patients remained with no evidence of disease for years until routine serial screening mammography was interpreted as suspicious. Each underwent a stereotactic biopsy of the ipsilateral breast corresponding to the mammographic abnormality. Pathology confirmed invasive ductal carcinoma. Both patients refused the recommended salvage mastectomy.

PRINCIPAL RESULTS: During a second attempt at breast conservation, sentinel lymph node mapping--which is typically contraindicated for patients with prior axillary surgery--revealed contralateral axillary uptake for both patients. The respective contralateral sentinel node was excised with pathology revealing no tumor in one case, and a microscopic focus of metastatic carcinoma in the second case.

MAJOR CONCLUSION: Some patients may benefit from sentinel lymph node mapping prior to salvage mastectomy. Identifying uptake in a contralateral sentinel lymph node may change the multi-disciplinary management of recurrent invasive breast cancer to include a contralateral axillary dissection, chemotherapy, and/or RT to the contralateral axilla.}, } @article {pmid16179626, year = {2005}, author = {Dogan, BE and Ceyhan, K and Tukel, S and Saylisoy, S and Whitman, GJ}, title = {Ductal dilatation as the manifesting sign of invasive ductal carcinoma.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {24}, number = {10}, pages = {1413-1417}, doi = {10.7863/jum.2005.24.10.1413}, pmid = {16179626}, issn = {0278-4297}, mesh = {Aged ; Breast Neoplasms/*diagnostic imaging/pathology/therapy ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/therapy ; Combined Modality Therapy ; Dilatation, Pathologic ; Female ; Humans ; Mammary Glands, Human/*pathology ; Mammography ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, } @article {pmid16177415, year = {2005}, author = {Nishino, TK and Wu, X and Johnson, RF}, title = {Thickness of molybdenum filter and squared contrast-to-noise ratio per dose for digital mammography.}, journal = {AJR. American journal of roentgenology}, volume = {185}, number = {4}, pages = {960-963}, doi = {10.2214/AJR.04.1489}, pmid = {16177415}, issn = {0361-803X}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Humans ; Mammography/*instrumentation ; *Molybdenum ; Monte Carlo Method ; Phantoms, Imaging ; Radiation Dosage ; Radiographic Image Enhancement/*instrumentation ; Radiometry/methods ; }, abstract = {OBJECTIVE: The objective of our study was to test whether the lesion-tissue contrast-to-noise ratio (CNR) at a given dose level can be improved by increasing the thickness of the molybdenum (Mo) filter currently used in digital mammography.

MATERIALS AND METHODS: We studied how the CNR between breast and a 5-mm simulated infiltrating ductal carcinoma (IDC) embedded in a 5-cm-thick breast changes with Mo filter thickness. We performed phantom imaging experiments by modifying the filter wheel of a Senographe 2000D unit with Mo filters that ranged from 15 to 90 microm in thickness. A 5-cm-thick 50% glandular-50% adipose breast phantom with a 5-mm insert simulating IDC was used as the phantom for all the cases. The CNRs between the breast phantom and the IDC insert were measured, and average glandular doses were calculated using a filtration-dependent X-ray spectra model and a breast dosimetry model based on a validated Monte Carlo simulation.

RESULTS: The lesion-tissue CNR at a given dose level increases with increasing Mo filter thickness from 15 to 90 microm. The measured squared CNR per dose increased by 8%, 14%, 17%, and 17% for 45-, 60-, 75-, and 90-microm Mo filters, respectively, compared with the standard 30-microm Mo filter. Meanwhile, the exposure times were increased by 35% (45 microm), 71% (60 microm), 177% (75 microm), and 229% (90 microm).

CONCLUSION: Increasing Mo filter thickness from 30 to 60 microm can increase lesion-tissue squared CNR per dose by 14% with a tolerable increase in the duration of exposure.}, } @article {pmid16173186, year = {2005}, author = {Hel-Or, Y and Hel-Or, H}, title = {Real-time pattern matching using projection kernels.}, journal = {IEEE transactions on pattern analysis and machine intelligence}, volume = {27}, number = {9}, pages = {1430-1445}, doi = {10.1109/TPAMI.2005.184}, pmid = {16173186}, issn = {0162-8828}, mesh = {*Algorithms ; *Artificial Intelligence ; Computer Graphics ; Computer Systems ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Imaging, Three-Dimensional/*methods ; Information Storage and Retrieval/methods ; Numerical Analysis, Computer-Assisted ; Pattern Recognition, Automated/*methods ; Signal Processing, Computer-Assisted ; *Subtraction Technique ; }, abstract = {A novel approach to pattern matching is presented in which time complexity is reduced by two orders of magnitude compared to traditional approaches. The suggested approach uses an efficient projection scheme which bounds the distance between a pattern and an image window using very few operations on average. The projection framework is combined with a rejection scheme which allows rapid rejection of image windows that are distant from the pattern. Experiments show that the approach is effective even under very noisy conditions. The approach described here can also be used in classification schemes where the projection values serve as input features that are informative and fast to extract.}, } @article {pmid16169726, year = {2006}, author = {Cho, MH and Yoon, JH and Jaegal, YJ and Choi, YD and Lee, JS and Lee, JH and Nam, JH and Choi, C and Lee, MC and Park, CS and Woo Juhng, S and Min, KW}, title = {Expression of cyclooxygenase-2 in breast carcinogenesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {15}, number = {3}, pages = {390-398}, doi = {10.1016/j.breast.2005.06.011}, pmid = {16169726}, issn = {0960-9776}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Cyclooxygenase 2/*biosynthesis ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2/*biosynthesis ; Survival Analysis ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in the successive steps of breast carcinogenesis and to determine its correlation with HER-2/neu and p53 expression in invasive ductal carcinomas of the breast. Immunohistochemical staining with anti-COX-2 antibody was performed in normal breast tissue, usual hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Expression of COX-2 in invasive ductal carcinoma was correlated with immunohistochemical expression of HER-2/neu and p53 protein. COX-2 expression was found to be progressively elevated along the continuum from normal breast tissue to invasive ductal carcinoma (P<0.001). COX-2 expression significantly correlated with p53 and HER-2/neu protein expression (P<0.05 and P<0.001). On multivariate analysis, only TNM stage and elevated COX-2 expression correlated with survival. Our results suggest that COX-2 may be involved in the carcinogenesis of the breast and may be an independent prognostic indicator in patients with invasive ductal carcinoma. HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.}, } @article {pmid16164939, year = {2005}, author = {Lim, SM and Lam, FL}, title = {Laparoscopic-assisted axillary dissection in breast cancer surgery.}, journal = {American journal of surgery}, volume = {190}, number = {4}, pages = {641-643}, doi = {10.1016/j.amjsurg.2005.06.031}, pmid = {16164939}, issn = {0002-9610}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/*surgery ; Carcinoma, Ductal, Breast/*pathology/*surgery ; Female ; Humans ; Laparoscopy ; Lymph Node Excision/*methods ; Mastectomy ; Middle Aged ; Neoplasm Staging ; }, abstract = {BACKGROUND: Significant morbidity such as pain, paresthesia, and arm stiffness has often been associated with axillary dissection for breast cancer. We report our experience of 30 patients with stage I and II invasive ductal carcinoma of the breast who underwent laparoscopic-assisted axillary dissection together with segmental mastectomy.

METHODS: Tumours were situated in the upper or lower lateral quadrants only. In all cases, initial exposure for axillary dissection was performed through the breast periareolar incision. A 10-mm 30 degrees laparoscope was introduced through the breast incision to gain entry to the axilla. A separate stab incision in the lower aspect of the axilla was used for introduction of the 5-mm Harmonic shears (Ethicon Endo-Surgery, Inc, Cincinnati, OH). A grasping forceps was introduced through the main incision alongside the endoscope. Subsequent axillary dissection was performed laparoscopically, and the axillary content was removed through the breast incision.

RESULTS: Average yield of lymph nodes was 15 (range 7 to 25). There were no intraoperative complications. Immediately postsurgery, all patients were able to fully mobilize the upper limb, facilitated by absence of an axillary scar. Patients also reported minimal pain, paresthesia, with no stiffness or frozen shoulder.

CONCLUSION: Laparoscopic-assisted axillary dissection offers a safe and improved approach to the axilla, which can be incorporated into breast cancer surgery.}, } @article {pmid16163035, year = {2005}, author = {Woodhams, R and Matsunaga, K and Iwabuchi, K and Kan, S and Hata, H and Kuranami, M and Watanabe, M and Hayakawa, K}, title = {Diffusion-weighted imaging of malignant breast tumors: the usefulness of apparent diffusion coefficient (ADC) value and ADC map for the detection of malignant breast tumors and evaluation of cancer extension.}, journal = {Journal of computer assisted tomography}, volume = {29}, number = {5}, pages = {644-649}, doi = {10.1097/01.rct.0000171913.74086.1b}, pmid = {16163035}, issn = {0363-8715}, mesh = {Adult ; Aged ; Aged, 80 and over ; Artifacts ; Breast Neoplasms/*diagnosis/pathology/surgery ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Statistics, Nonparametric ; }, abstract = {The authors used breast diffusion-weighted imaging (DWI) to diagnose breast cancer and identify cancer extension. Isotropic DWI was performed with EPI. The apparent diffusion coefficient (ADC) value was calculated and displayed on an ADC map. The authors compared between the distribution of low ADC values and pathologic cancer extension. The mean ADC value of breast cancer was 1.12 +/- 0.24 x 10(-3) mm/s, which was lower than that of normal breast tissue. The ADC value for invasive ductal carcinoma was lower than that of noninvasive ductal carcinoma. The sensitivity of the ADC value for breast cancer using a threshold of less than 1.6 x 10(-3) mm/s was 95%. Seventy-five percent of all cases showed precise distribution of low ADC value as cancer extension. The causes of underestimation were susceptibility artifact from bleeding and the limit of spatial resolution. Benign proliferative change showed a low ADC value. The authors conclude that DWI has a potential for clinical appreciation in detecting breast cancer.}, } @article {pmid16154043, year = {2005}, author = {Huck, B and Steck, T and Habersack, M and Dietl, J and Kämmerer, U}, title = {Pregnancy associated hormones modulate the cytokine production but not the phenotype of PBMC-derived human dendritic cells.}, journal = {European journal of obstetrics, gynecology, and reproductive biology}, volume = {122}, number = {1}, pages = {85-94}, doi = {10.1016/j.ejogrb.2005.02.017}, pmid = {16154043}, issn = {0301-2115}, mesh = {Cytokines/*biosynthesis ; Dendritic Cells/*drug effects/metabolism ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Estradiol/administration & dosage/*pharmacology ; Female ; Humans ; Lymphocyte Activation/drug effects ; Male ; Monocytes/drug effects/metabolism ; Phenotype ; Pregnancy ; Progesterone/administration & dosage/*pharmacology ; T-Lymphocytes/immunology ; }, abstract = {OBJECTIVE: Dendritic cells (DC) play a central role in initiating and polarizing immune responses. As effects of pregnancy associated hormones on phenotype and function of DC are unknown, our objective was to test the influence of progesterone, beta-estradiol and betaHCG on immature (iDC) and mature (mDC) DC.

STUDY DESIGN: DC generated from peripheral-blood-monocytes were exposed to different doses of hormones. DC phenotype was determined by FACS-analysis of surface marker expression (CD40, CD86, CD83 and HLA-DR). Modifications in the secretion of cytokines (IL12p70, IL-18, IL-10, IL-6, TNFalpha) and chemokines (MDC, IL-8) were analysed by ELISA. T cell stimulatory capacity of mDC was assessed by mixed lymphocyte reaction.

RESULTS: Incubation with progesterone or estradiol resulted in a significant upregulation of IL-10 production by iDC and mDC. Combinations of progesterone and betaHCG or estradiol respectively induced a significant decrease in production of IL-18 by mDC. No significant changes could be observed in surface marker expression or T cell stimulatory capacity, neither in cultures of DC matured under influence of progesterone, estradiol nor betaHCG.

CONCLUSIONS: PBMC-derived DC seem to be relatively stable against the influence of pregnancy associated hormones apart from particular effects on cytokine production which partly could contribute to the modification of immune responses observed in normal early pregnancy.}, } @article {pmid16142429, year = {2005}, author = {Lim, SM and Kum, CK and Lam, FL}, title = {Nerve-sparing axillary dissection using the da Vinci Surgical System.}, journal = {World journal of surgery}, volume = {29}, number = {10}, pages = {1352-1355}, pmid = {16142429}, issn = {0364-2313}, mesh = {Axilla/innervation/surgery ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; Lymph Node Excision/*instrumentation/methods ; Mastectomy ; Middle Aged ; *Robotics ; }, abstract = {This is an initial report of a new method of axillary dissection via a periareolar incision and an 8 mm incision in the axilla with the da Vinci Surgical System. The 10x magnification and three-dimensional image, together with the versatility and precision of the robotic telemanipulators, has enabled us to perform nerve-sparing axillary dissection in four patients with invasive ductal carcinoma of the breast undergoing segmental (conservative) excision and level II axillary dissection. The time for the robotic axillary dissection ranged from 30 to 105 minutes (average 70.5 minutes). The average number of lymph nodes retrieved was 13 (11, 11, 13, and 17, respectively). Postoperatively all four patients recovered well and were discharged the next day. The robotic system can enhance the surgeon's ability by providing a high-definition, magnified, three-dimensional view of the operative field, intuitively controlled articulating instruments, and elimination of tremors; and it has potential benefits for the patient.}, } @article {pmid16131446, year = {2005}, author = {Cejas, P and García-Cabezas, MA and Casado, E and Barriuso, J and Fresno, JA and Díaz, E and Belda-Iniesta, C and Castro, J and Espinosa, E and Zamora, P and Feliu, J and Redondo, A and Hardisson, DA and González-Barón, M}, title = {Localisation of COX-2 protein is different in breast ductal carcinoma and adjacent non-tumour ductal epithelium.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {7}, number = {6}, pages = {239-243}, pmid = {16131446}, issn = {1699-048X}, mesh = {Adult ; Aged ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Epithelium/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; RNA, Messenger/analysis ; }, abstract = {INTRODUCTION: A number of findings suggest that cyclooxygenase-2 (COX-2) is overexpressed in breast tumours. However, there is a lack of consensus in the literature regarding the pattern of expression of this protein in invasive breast ductal carcinoma and in the adjacent non-tumour ductal epithelium. This study compares the expression of COX-2 mRNA and protein in breast ductal carcinoma relative to non-tumour breast tissue.

MATERIAL AND METHODS: We analysed the expression of COX-2 mRNA by quantitative PCR, and COX-2 protein by immunohistochemistry in invasive ductal carcinoma as well as in non-tumour adjacent ductal epithelium from 34 breast biopsies diagnosed as being invasive ductal carcinoma. As control, we analysed expression of COX-2 protein by immunohistochemistry in surgically-resected benign breast lesions.

RESULTS: Our results show that COX-2 mRNA and protein are overexpressed in non-tumour ductal epithelium compared with invasive ductal carcinoma. However, the pattern of the protein expression is different in tumour and non-tumour tissue: COX-2 protein is expressed predominantly in the membrane of the non-tumour ductal epithelium (including in benign breast lesions) while, in invasive ductal carcinoma cells, it is localised in the cytoplasm.

CONCLUSIONS: The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.}, } @article {pmid16127252, year = {2005}, author = {Woodhams, R and Matsunaga, K and Kan, S and Hata, H and Ozaki, M and Iwabuchi, K and Kuranami, M and Watanabe, M and Hayakawa, K}, title = {ADC mapping of benign and malignant breast tumors.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {4}, number = {1}, pages = {35-42}, doi = {10.2463/mrms.4.35}, pmid = {16127252}, issn = {1347-3182}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Artifacts ; *Artificial Intelligence ; Breast Neoplasms/*diagnosis ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Information Storage and Retrieval/methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The purpose of this study was to investigate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value in differentiating benign and malignant breast lesions and evaluating the detection accuracy of the cancer extension.

MATERIALS AND METHODS: We used DWI to obtain images of 191 benign and malignant lesions (24 benign, 167 malignant) before surgical excision. The ADC values of the benign and malignant lesions were compared, as were the values of noninvasive ductal carcinoma (NIDC) and invasive ductal carcinoma (IDC). We also evaluated the ADC map, which represents the distribution of ADC values, and compared it with the cancer extension.

RESULTS: The mean ADC value of each type of lesion was as follows: malignant lesions, 1.22+/-0.31 x 10(-3) mm2/s; benign lesions, 1.67+/-0.54 x 10(-3) mm2/s; normal tissues, 2.09+/-0.27 x 10(-3) mm2/s. The mean ADC value of the malignant lesions was statistically lower than that of the benign lesions and normal breast tissues. The ADC value of IDC was statistically lower than that of NIDC. The sensitivity of the ADC value for malignant lesions with a threshold of less than 1.6 x 10(-3) mm2/s was 95% and the specificity was 46%. A full 75% of all malignant cases exhibited a near precise distribution of low ADC values on ADC maps to describe malignant lesions. The main causes of false negative and underestimation of cancer spread were susceptibility artifact because of bleeding and tumor structure. Major histologic types of false-positive lesions were intraductal papilloma and fibrocystic diseases. Fibrocystic diseases also resulted in overestimation of cancer extension.

CONCLUSIONS: DWI has the potential in clinical appreciation to detect malignant breast tumors and support the evaluation of tumor extension. However, the benign proliferative change remains to be studied as it mimics the malignant phenomenon on the ADC map.}, } @article {pmid16118805, year = {2005}, author = {Peppercorn, J and Herndon, J and Kornblith, AB and Peters, W and Ahles, T and Vredenburgh, J and Schwartz, G and Shpall, E and Hurd, DD and Holland, J and Winer, E}, title = {Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: results from Cancer and Leukemia Group B 9066.}, journal = {Cancer}, volume = {104}, number = {8}, pages = {1580-1589}, doi = {10.1002/cncr.21363}, pmid = {16118805}, issn = {0008-543X}, support = {CA02599/CA/NCI NIH HHS/United States ; CA03927/CA/NCI NIH HHS/United States ; CA04326/CA/NCI NIH HHS/United States ; CA04457/CA/NCI NIH HHS/United States ; CA07968/CA/NCI NIH HHS/United States ; CA08025/CA/NCI NIH HHS/United States ; CA11789/CA/NCI NIH HHS/United States ; CA14028/CA/NCI NIH HHS/United States ; CA16450/CA/NCI NIH HHS/United States ; CA21060/CA/NCI NIH HHS/United States ; CA31809/CA/NCI NIH HHS/United States ; CA31946/CA/NCI NIH HHS/United States ; CA31983/CA/NCI NIH HHS/United States ; CA32291/CA/NCI NIH HHS/United States ; CA33601/CA/NCI NIH HHS/United States ; CA35279/CA/NCI NIH HHS/United States ; CA37135/CA/NCI NIH HHS/United States ; CA41287/CA/NCI NIH HHS/United States ; CA42777/CA/NCI NIH HHS/United States ; CA47545/CA/NCI NIH HHS/United States ; CA47559/CA/NCI NIH HHS/United States ; CA47577/CA/NCI NIH HHS/United States ; CA47642/CA/NCI NIH HHS/United States ; CA60138/CA/NCI NIH HHS/United States ; CA77440/CA/NCI NIH HHS/United States ; CA77651/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; *Bone Marrow Transplantation ; Breast Neoplasms/psychology/*therapy ; Carmustine/administration & dosage ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Dose-Response Relationship, Drug ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; *Quality of Life ; Survival Rate ; Time Factors ; Transplantation, Autologous ; }, abstract = {BACKGROUND: The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting.

METHODS: Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had > or = 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS).

RESULTS: At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved.

CONCLUSIONS: Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline.}, } @article {pmid16110288, year = {2005}, author = {Kuroda, H and Sakamoto, G and Ohnisi, K and Itoyama, S}, title = {Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {3}, pages = {189-195}, doi = {10.2325/jbcs.12.189}, pmid = {16110288}, issn = {1340-6868}, mesh = {Adenocarcinoma, Clear Cell/genetics/*metabolism/pathology ; Adult ; Aged ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Genes, erbB-2 ; Glycogen/*metabolism ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; }, abstract = {BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen.

METHODS: The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status.

RESULTS: Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis.

CONCLUSION: Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.}, } @article {pmid16110134, year = {2005}, author = {Abrial, C and Mouret-Reynier, MA and Amat, S and Sillet-Bach, I and Bougnoux, P and Delva, R and Cure, H and Dauplat, J and Penault-Llorca, F and Chollet, P}, title = {Tumor parameters, clinical and pathological responses, medical management, and survival through time on 710 operable breast cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {22}, number = {3}, pages = {233-240}, pmid = {16110134}, issn = {1357-0560}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/*pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; History, Medieval ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Treatment Outcome ; }, abstract = {The aim of the current study is an analysis of tumor parameters, clinical and pathological responses, medical management, and survival on 710 operable breast cancer patients who received neoadjuvant chemotherapy from 1982 to 2004 and were grouped into four successive periods according to diagnosis date: (1) 1982-1989; (2) 1990-1994; (3) 1995-1999; and (4) 2000-2004. Patients were treated by different neoadjuvant chemotherapies combinations: AVCF/M, TNCF, NEM, NET, TAXOTERE, FEC 50, 75, 100, FAC 50, and TAXOTERE-TNCF, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After primary chemotherapy, patients underwent a surgery and a radiotherapy. In case of significant residual disease, some patients received additional courses of chemotherapy. In addition, menopausal patients with hormonal receptor-positive tumors received tamoxifen for 5 yr. Clinical factors had some remarkable variations with time. The median age of the patients was 49.5 yr (range, 26-81). The size of the tumor was significantly greater from 1995; conversely, clinical lymph-node involvement was lower in period 4 than in the first period. The percentage of invasive ductal carcinoma and of SBR III tumors increased about 20% from 1982-1989 to 2000-2004. The number of positive hormonal receptors increased from 38.3% in period 1 to 74% in period 4. The clinical response rate improved recently from before 1990. The pathological response rate was greater in periods 2 and 3 than in periods 1 and 4. An adjuvant hormonotherapy became progressively more frequently given (44.7 for period 1 and 73.3% for period 4). Finally, no significant difference was found when we compared overall and disease-free survival through the four periods. It appears that the progressive increase of tumor burden was compensated by more effective treatments.}, } @article {pmid16107908, year = {2005}, author = {Demirbag, R and Yilmaz, R and Erel, O and Gultekin, U and Asci, D and Elbasan, Z}, title = {The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.}, journal = {The Canadian journal of cardiology}, volume = {21}, number = {10}, pages = {851-855}, pmid = {16107908}, issn = {0828-282X}, mesh = {Age Distribution ; Aged ; Analysis of Variance ; Antioxidants/*metabolism ; Cardiomyopathy, Dilated/*epidemiology/*etiology/physiopathology ; Case-Control Studies ; Cohort Studies ; Female ; Heart Function Tests ; Humans ; Incidence ; Male ; Middle Aged ; Oxidation-Reduction ; Oxidative Stress/*physiology ; Probability ; Prognosis ; Reference Values ; Risk Assessment ; Sensitivity and Specificity ; Severity of Illness Index ; Sex Distribution ; Survival Rate ; }, abstract = {BACKGROUND: It has been suggested that oxidative stress may have a role in the etiopathogenesis of congestive heart failure.

OBJECTIVES: To investigate and compare the oxidative-antioxidative status and oxidative stress index (OSI) of patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy volunteers, and to determine the relationship between total antioxidant capacity (TAC) and ejection fraction (EF).

METHODS: Twenty-eight patients with IDC and 24 control subjects were enrolled in the study. Antioxidative status was evaluated by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative status was evaluated by measuring the total peroxide level. The per cent ratio of TAC to total peroxide level was accepted as the OSI. EF was measured using Simpson's method.

RESULTS: TAC and vitamin C and thiol levels of plasma were found to be significantly lower in patients with IDC than in control subjects (P < 0.001). In contrast, total peroxide levels and OSIs were significantly higher in patients with IDC than in control subjects (P = 0.002 and P = 0.002, respectively). An important positive correlation was found between TAC and EF (r = 0.772; P < 0.001). On the other hand, significant negative correlations were found between EF and OSI and between EF and total peroxide levels in patients.

CONCLUSIONS: Oxidants are increased and antioxidants are decreased in patients with IDC; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. There is a significant correlation between the potency of oxidative stress and the severity of IDC. It is believed that supplementation of antioxidants in the treatment of IDC may be helpful to these patients.}, } @article {pmid16102447, year = {2005}, author = {Moloney, ED and Egan, JJ and Kelly, P and Wood, AE and Cooper, LT}, title = {Transplantation for myocarditis: a controversy revisited.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {24}, number = {8}, pages = {1103-1110}, doi = {10.1016/j.healun.2004.06.015}, pmid = {16102447}, issn = {1053-2498}, mesh = {Adult ; Biopsy, Needle ; Echocardiography, Transesophageal ; Follow-Up Studies ; Graft Survival ; Heart Failure/*complications/diagnosis ; Heart Function Tests ; Heart Transplantation/adverse effects/*methods ; Humans ; Immunohistochemistry ; Immunosuppressive Agents/*therapeutic use ; Male ; Myocarditis/diagnostic imaging/etiology/*pathology/*surgery ; Postoperative Complications/drug therapy/pathology ; Risk Assessment ; Severity of Illness Index ; }, abstract = {Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide, approximately 45% of all heart transplants are performed for IDC and up to 8% for myocarditis. Early reports suggested that survival after transplantation for myocarditis was poor and patients had an increased risk of rejection. More recently, larger case series suggest that overall survival after transplantation for myocarditis is similar to survival after transplantation for other causes. However, certain disorders, including cardiac sarcoidosis and giant cell myocarditis (GCM), require heightened surveillance for post-transplantation disease recurrence. We present the case of a 42-year-old man with recurrence of GCM 8 years after transplantation and review the literature on the role of cardiac transplantation for patients with myocarditis.}, } @article {pmid16101174, year = {2005}, author = {Nio, Y and Omori, H and Hashimoto, K and Itakura, M and Koike, M and Yano, S and Toga, T and Higami, T and Maruyama, R}, title = {Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.}, journal = {Anticancer research}, volume = {25}, number = {5}, pages = {3523-3529}, pmid = {16101174}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/drug therapy/*metabolism/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/drug therapy/*metabolism/pathology/surgery ; Proto-Oncogene Proteins c-kit/*biosynthesis ; Transforming Growth Factor beta/*metabolism ; Transforming Growth Factor beta1 ; }, abstract = {BACKGROUND: The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas.

PATIENTS AND METHODS: This study included 91 pancreatic IDC patients who received a pancreatectomy between 1982 and 2003. The expression of KIT and TGF-beta1 was analyzed by immunohistochemistry.

RESULTS: KIT and TGF-beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression correlated inversely with nodal involvement, but KIT expression did not correlate with any clinicopathological factors. KIT expression had no significant influence on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co-expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+) IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a significant effect on the efficacy of adjuvant chemotherapy (ACT). In multivariate analysis, TGF-beta1 expression was one of the significant variables for survival in IDC patients overall, but KIT expression was not.

CONCLUSION: TGF-beta1 expression is suggested to have a significant influence on c-kit-mediated cell proliferation in human pancreatic IDCs.}, } @article {pmid16094691, year = {2005}, author = {Pruenster, M and Wilflingseder, D and Bánki, Z and Ammann, CG and Muellauer, B and Meyer, M and Speth, C and Dierich, MP and Stoiber, H}, title = {C-type lectin-independent interaction of complement opsonized HIV with monocyte-derived dendritic cells.}, journal = {European journal of immunology}, volume = {35}, number = {9}, pages = {2691-2698}, doi = {10.1002/eji.200425940}, pmid = {16094691}, issn = {0014-2980}, mesh = {Antibodies, Monoclonal/immunology/pharmacology ; CD4 Antigens/immunology ; Cell Adhesion Molecules/immunology ; Coculture Techniques ; Complement C3/*immunology ; Dendritic Cells/*immunology/*virology ; HIV/*immunology ; HIV Envelope Protein gp120/*immunology ; HIV Infections/*immunology ; Humans ; Immunity, Innate/immunology ; Intercellular Adhesion Molecule-1/immunology ; Lectins, C-Type/immunology ; Mannans/immunology ; Protein Binding ; Receptors, Cell Surface/immunology ; T-Lymphocytes/immunology ; }, abstract = {HIV directly activates the complement cascade and is, therefore, opsonized with C3-cleavage products in vivo. This cloud of C3 fragments on the viral surface may impair the interaction of the HIV envelope glycoproteins gp120/gp41 with C-type lectins expressed on immature dendritic cells (iDC). Therefore, we determined the accessibility of gp120 after opsonization and compared the interaction of DC with non-opsonized or complement-opsonized HIV. The recognition of native gp120 was drastically impaired when the virus was covered by complement. Independent of opsonization, similar amounts of HIV bound to DC. The interaction of iDC and the infection of DC-PBL co-cultures with non-opsonized virus was significantly reduced by mannan and antibodies which inhibit the ICAM-1-CR3 interaction. The binding of opsonized virus to iDC was reduced by an anti-CR3-antibody, which interferes with the binding of C3 fragments, but was not affected by mannan. Complement enhanced the HIV infection of DC and DC-PBL co-cultures significantly. Mannan did not inhibit the complement-dependent enhancement of infection. Thus, non-opsonized and opsonized HIV interacted with iDC, although the binding mechanisms seemed to differ. As HIV is opsonized in vivo, the C-type lectin-independent interaction of opsonized viruses with iDC has to be taken into account.}, } @article {pmid16093623, year = {2004}, author = {Kuroki, Y and Nasu, K and Kuroki, S and Murakami, K and Hayashi, T and Sekiguchi, R and Nawano, S}, title = {Diffusion-weighted imaging of breast cancer with the sensitivity encoding technique: analysis of the apparent diffusion coefficient value.}, journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine}, volume = {3}, number = {2}, pages = {79-85}, doi = {10.2463/mrms.3.79}, pmid = {16093623}, issn = {1347-3182}, mesh = {Artifacts ; Breast Neoplasms/*diagnosis ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The usefulness of diffusion-weighted imaging (DWI) in the field of neuroradiology has been established. Despite its high contrast resolution, DWI has the disadvantages of susceptibility artifact and chemical shift artifact. We performed DWI of breast cancer with the sensitivity encoding (SENSE) technique.

METHODS: The subjects were 60 female patients with breast mass. All patients underwent MRI including SENSE-DWI and were diagnosed histologically. Of these patients, 55 were diagnosed with breast cancer and the remaining five were diagnosed with benign mass. The histological diagnoses of breast cancer were as follows: 39 cases of invasive ductal carcinoma (IDC); 11 cases of IDC with a predominant intraductal component and non IDC (pure or predominant NIDC); and five cases of special types of cancer. The MR system used was a Gyroscan Intera 1.5T (Philips Medical Systems). In addition to routine MRI for breast cancer, including contrast-enhanced dynamic, SENSE-DWI was obtained. The accuracy of the positional information of SENSE-DWI was visually compared with that of conventional images. The apparent diffusion coefficient (ADC) values of breast mass were analyzed with SENSE-DWI.

RESULTS: The accuracy of positional information was adequate for diagnosing of all patients. The mean ADC value of breast cancer was 1.021x10(-3) mm2/s and that of benign mass was 1.488x10(-3) mm2/s (p=0.0002). The mean ADC value of IDC was 0.968x10(-3) mm2/s and that of pure or predominant NIDC was 1.218x10(-3) mm2/s (p=0.0011).

CONCLUSION: SENSE-DWI was of sufficient quality to support diagnosis of breast mass. SENSE-DWI may permit the acquisition of more detailed information about lesions, including tumor cellularity, that is difficult to obtain with conventional techniques.}, } @article {pmid16091843, year = {2005}, author = {García-Castellanos, R and Bonet-Figueredo, R and Pallarés, I and Ventura, S and Avilés, FX and Vendrell, J and Gomis-Rütha, FX}, title = {Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {62}, number = {17}, pages = {1996-2014}, doi = {10.1007/s00018-005-5174-4}, pmid = {16091843}, issn = {1420-682X}, mesh = {Amino Acid Sequence ; Animals ; Antigens/*chemistry/*pharmacology ; Carboxypeptidase B/antagonists & inhibitors/chemistry ; Carboxypeptidases A/*antagonists & inhibitors/*chemistry ; Crystallography, X-Ray ; Enzyme Precursors/*antagonists & inhibitors/*chemistry ; Humans ; Male ; Mice ; Molecular Sequence Data ; Prostatic Neoplasms/*enzymology ; Protein Conformation ; }, abstract = {Treatment of advanced stages of prostate carcinoma with histone-deacetylase inhibitors entails expression of human procarboxypeptidase-A4 (hPCPA4). The three-dimensional structure of hPCPA4 has been solved and shows the features of related metallocarboxypeptidase zymogens, with a preformed alpha/beta/-hydrolase active-enzyme moiety (hCPA4) and an inhibiting pro-domain (PD). The protease moiety recalls a sphere, out of which a spherical cone has been cut. This results in a funnel-like structure, at the bottom of which the active-site cleft resides. The border of this funnel is shaped by loops, which are responsible for the interaction with the PD, characterised by a large interface area and relatively few contacts. Such an inhibitory mode is evocative of the recently reported structure of the human inhibitor latexin in its complex with hCPA4. The main contacting structure of latexin is similar to the one employed for PD inhibition. In both cases, active-site blocking relies mainly on a loop provided by the central part of a beta sheet.}, } @article {pmid16086078, year = {2005}, author = {Bassarova, AV and Nesland, JM and Sedloev, T and Lilleby, W and Hristova, SL and Trifonov, DY and Torlakovic, E}, title = {Simultaneous bilateral breast carcinomas: a category with frequent coexpression of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53.}, journal = {International journal of surgical pathology}, volume = {13}, number = {3}, pages = {239-246}, doi = {10.1177/106689690501300302}, pmid = {16086078}, issn = {1066-8969}, mesh = {Adenocarcinoma/metabolism/*secondary ; Adult ; Aged ; Axilla ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Ki-67 Antigen/metabolism ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis/pathology ; Middle Aged ; Neoplasm Proteins/*metabolism ; *Neoplasms, Multiple Primary ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.}, } @article {pmid16084677, year = {2006}, author = {Tang, MW and Kwok, TC and Hui, E and Woo, J}, title = {Intermittent versus indwelling urinary catheterization in older female patients.}, journal = {Maturitas}, volume = {53}, number = {3}, pages = {274-281}, doi = {10.1016/j.maturitas.2005.05.014}, pmid = {16084677}, issn = {0378-5122}, mesh = {Aged ; Aged, 80 and over ; Bacteriuria/epidemiology/etiology ; Catheters, Indwelling ; Female ; Humans ; Prospective Studies ; Treatment Outcome ; Urinary Catheterization/instrumentation/*methods ; Urinary Retention/*therapy ; }, abstract = {OBJECTIVES: To compare the use of intermittent and indwelling catheterization in older female patients with urinary retention.

METHODS: A randomized, 2-week prospective study in a geriatric rehabilitation ward. Female patients of age 65 years and older with post-voiding residual urine volume (PVRU) persistently > or = 300 ml were randomly assigned to one of the two groups: intermittent catheterization (IMC group, n=36) and indwelling catheterization (IDC group, n=45). The primary outcome was the proportion of subjects being catheter-free and had a PVRU < 150 ml on day 14. The secondary outcomes were the time to become catheter-free and the rate of bacteriuria on day 14.

RESULTS: Sixteen out of 27 (59.3%) in the IMC group versus 27 out of 39 (69.2%) in the IDC group achieved the primary outcome on day 14 (P=.403) without significant difference in the PVRU. The IMC and IDC groups took a mean of 8.6+/-3.3 and 9.2+/-4.0 days to become catheter-free, respectively (P=.609). Fourteen out of 22 (63.6%) in the IMC group versus 21 out of 34 (61.8%) in the IDC group had bacteriuria on day 14 (P=.888).

CONCLUSION: Given the similar success rate of regaining bladder voiding function, the similar rate of bacteriuria and considering that the IMC group only underwent a median of 3 times of intermittent catheterization, we believe that the approach of intermittent urinary catheterization when required would be justified in managing elderly female urinary retention in rehabilitation ward as the presence of indwelling catheters would hinder rehabilitation and adversely affect patient quality of life.}, } @article {pmid16080559, year = {2005}, author = {Okada, K and Osaki, M and Araki, K and Ishiguro, K and Ito, H and Ohgi, S}, title = {Expression of hypoxia-inducible factor (HIF-1alpha), VEGF-C and VEGF-D in non-invasive and invasive breast ductal carcinomas.}, journal = {Anticancer research}, volume = {25}, number = {4}, pages = {3003-3009}, pmid = {16080559}, issn = {0250-7005}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal/*metabolism/pathology ; Female ; Fibroadenoma/metabolism/pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Immunohistochemistry ; Neoplasm Invasiveness ; Transcription Factors/*biosynthesis ; Vascular Endothelial Growth Factor C/*biosynthesis ; Vascular Endothelial Growth Factor D/*biosynthesis ; }, abstract = {BACKGROUND: Hypoxia-inducible factor 1 alpha (HIF-1alpha) is a transcription factor that may play an important role in tumour growth and metastasis by its regulation of angiogenesis and lymphangiogenesis to survive cellular hypoxia. Lymphangiogenesis is promoted by vascular endothelial growth factors (VEGF)-C and VEGF-D, but the correlation between the expression of HIF-1alpha and VEGF-C or VEGF-D in human breast carcinoma is not well elucidated. This study examined the pathobiological role of these molecules in human breast ductal carcinoma.

MATERIALS AND METHODS: The expressions of HIF-1alpha, VEGF-C and VEGF-D were analyzed in 10 normal mammary epithelia, 12 fibroadenomas, 20 ductal carcinomas in situ (DCISs and 36 invasive ductal carcinomas (IDCs) by immunohistochemistry, comparing clinicopathological parameters.

RESULTS: HIF-1alpha expression in nuclei was found in DCIS and IDC, but not in normal or fibroadenoma cells. The HIF-1alpha labelling index was significantly correlated with the degree of VEGF-C expression in IDC (p < 0.001), but not in DCIS. HIF-1alpha expression was significantly correlated with tumour necrosis and with the Van Nuys prognostic index (VNPI) (p < 0.05, p < 0.05, respectively) in the 20 DCISs. On the other hand, VEGF-D levels, but not those of HIF-1alpha and VEGF-C, were significantly higher in cases with lymph node metastasis and estrogen receptor expression in carcinoma cells (p < 0.01, p < 0.05, respectively) in the 36 IDCs.

CONCLUSION: These findings suggest that HIF-1alpha is expressed in the early stage of mammary carcinogenesis, in which the expression correlates with necrosis in the DCISs and with VEGF-C expression in the IDCs, the latter resulting in a higher frequency of metastasis to regional lymph nodes.}, } @article {pmid16053511, year = {2005}, author = {Peng, DF and Kanai, Y and Sawada, M and Ushijima, S and Hiraoka, N and Kosuge, T and Hirohashi, S}, title = {Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas.}, journal = {Cancer science}, volume = {96}, number = {7}, pages = {403-408}, doi = {10.1111/j.1349-7006.2005.00071.x}, pmid = {16053511}, issn = {1347-9032}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Pancreatic Ductal/*chemistry/genetics ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/*analysis ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/*chemistry/genetics ; Precancerous Conditions/*chemistry/genetics ; Prognosis ; Up-Regulation ; }, abstract = {Aberrant DNA methylation has been shown to play an important role during multistage carcinogenesis in various human organs. The aim of the present study was to evaluate the significance of DNA methyltransferase 1 (DNMT1) protein expression during pancreatic carcinogenesis. Immunohistochemical analysis of DNMT1 in 48 peripheral pancreatic duct epithelia showing no remarkable histological findings without an inflammatory background (DE), 54 peripheral pancreatic duct epithelia with an inflammatory background (DEI), 188 pancreatic intraepithelial neoplasias (PanIN), and 220 areas of invasive ductal carcinoma from surgical specimens resected from 100 patients, was carried out. The average incidence of DNMT1 immunoreactivity increased progressively from DE to DEI (P = 0.003), from DE and DEI to PanIN (P < 0.0001), among PanIN with different grades of dysplasia (from PanIN I to PanIN II, P = 0.0012), from PanIN to invasive ductal carcinomas (P < 0.0001) and among invasive ductal carcinomas with different grades of histological differentiation (from well or moderately to poorly differentiated adenocarcinomas, P < 0.0001). High-level DNMT1 protein expression in invasive ductal carcinomas was correlated significantly with an advanced t category (P = 0.0224) and an advanced stage (P = 0.0294). Moreover, patients with invasive ductal carcinomas showing high-level DNMT1 protein expression had a poorer outcome (P = 0.0469). These data suggest that increased DNMT1 protein expression participates in multistage pancreatic carcinogenesis from the precancerous stage to malignant progression of ductal carcinomas and may be a biological predictor of poor prognosis.}, } @article {pmid16052519, year = {2006}, author = {Ohuchida, K and Mizumoto, K and Yamada, D and Fujii, K and Ishikawa, N and Konomi, H and Nagai, E and Yamaguchi, K and Tsuneyoshi, M and Tanaka, M}, title = {Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer.}, journal = {International journal of cancer}, volume = {118}, number = {2}, pages = {405-411}, doi = {10.1002/ijc.21317}, pmid = {16052519}, issn = {0020-7136}, mesh = {Biomarkers, Tumor/analysis ; Case-Control Studies ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Mucin 5AC ; Mucin-1/*analysis/biosynthesis/genetics ; Mucins/*analysis/biosynthesis/genetics ; Pancreatic Juice/chemistry ; Pancreatic Neoplasms/*diagnosis ; Polymerase Chain Reaction ; Preoperative Care ; RNA, Messenger/analysis ; Tumor Cells, Cultured ; }, abstract = {Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer.}, } @article {pmid16049287, year = {2005}, author = {Saitou, M and Goto, M and Horinouchi, M and Tamada, S and Nagata, K and Hamada, T and Osako, M and Takao, S and Batra, SK and Aikou, T and Imai, K and Yonezawa, S}, title = {MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.}, journal = {Journal of clinical pathology}, volume = {58}, number = {8}, pages = {845-852}, pmid = {16049287}, issn = {0021-9746}, support = {R01 CA078590/CA/NCI NIH HHS/United States ; CA 78590/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Carcinoma, Pancreatic Ductal/*metabolism/pathology/secondary ; Disease Progression ; Female ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin-4 ; Mucins/*metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Pancreas/metabolism ; Pancreatic Neoplasms/*metabolism/pathology ; Prognosis ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.

AIMS: To investigate the prognostic significance of MUC4 expression in IDC.

METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.

RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.

CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.}, } @article {pmid16047331, year = {2005}, author = {Brem, RF and Rapelyea, JA and Zisman, G and Hoffmeister, JW and Desimio, MP}, title = {Evaluation of breast cancer with a computer-aided detection system by mammographic appearance and histopathology.}, journal = {Cancer}, volume = {104}, number = {5}, pages = {931-935}, doi = {10.1002/cncr.21255}, pmid = {16047331}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Lobular/diagnosis ; *Diagnosis, Computer-Assisted ; Female ; Humans ; *Mammography ; Middle Aged ; }, abstract = {BACKGROUND: The objective of this study was to evaluate the performance of a computer-aided detection (CAD) system for the detection of breast cancer, based on mammographic appearance and histopathology.

METHODS: From 1000 consecutive screening mammograms from women with biopsy-proven breast carcinoma, 273 mammograms were selected randomly for retrospective evaluation by CAD. The sensitivity of the CAD system for breast cancer was assessed from the proportion of masses and microcalcifications detected. The corresponding tumor histopathologies also were evaluated. Normal mammograms (n = 155 patients) were used to determine the false-positive rate of the system.

RESULTS: Of the 273 breast carcinomas, 149 appeared mammographically as masses, and 88 appeared as microcalcifications, including 36 carcinomas that presented as mixed lesions. The CAD system marked 125 of 149 masses correctly (84%), marked 86 of 88 microcalcifications correctly (98%), and marked 32 of 36 of mixed lesions correctly (89%.). The system showed a high sensitivity for the detection of ductal carcinoma in situ (95%; 73 of 77 lesions), invasive lobular carcinoma (95%; 18 of 19 lesions), invasive ductal carcinoma (85%; 125 of 147 lesions), and invasive mammary carcinoma (90%; 27 of 30 lesions). The highest CAD system sensitivity was for all invasive carcinomas that presented as microcalcifications (100%). On normal mammograms, there was an average of 1.3 false-positive CAD marks per image.

CONCLUSIONS: The CAD system correctly marked a large majority of biopsy-proven breast cancers, with a greater sensitivity for lesions with microcalcifications and without significant impact of performance based on tumor histopathology. CAD was highly effective in detecting invasive lobular carcinoma (sensitivity, 95%) and ductal carcinoma in situ (sensitivity, 95%). CAD represents a useful tool for the detection of breast cancer.}, } @article {pmid16047330, year = {2005}, author = {Kaufman, SA and Dipetrillo, TA and Ruthazer, R and Wazer, DE}, title = {MammoSite excision volume as a predictor for residual disease.}, journal = {Cancer}, volume = {104}, number = {5}, pages = {906-912}, doi = {10.1002/cncr.21269}, pmid = {16047330}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Brachytherapy/*instrumentation ; Breast Neoplasms/pathology/*radiotherapy ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; }, abstract = {BACKGROUND: The MammoSite catheter is a brachytherapy device used for accelerated partial breast irradiation. Currently, it is available as 2 spherically shaped balloons meant to fill 70-cc and 120-cc cavity volumes. This study was designed to define the relation of these excision volumes to the likelihood of microscopically detectable, residual disease based on tumor size, margin status, patient age, and histology.

METHODS: The study data base was comprised of 531 patients with Stage 0, I, and II breast carcinoma (using American Joint Committee on Cancer staging criteria) who received breast-conserving therapy and underwent surgical reexcision. Patients in the data base were stratified based on the volume of their initial excision: < or = 70 cc versus > 70 cc and < or = 120 cc versus > 120 cc.

RESULTS: Surgical margin size was found to be a strong predictor of residual disease both for patients with smaller excision volumes (P = 0.0014) and patients with larger excision volumes (P = 0.0003); histology (extensive intraductal component [EIC] or pure ductal carcinoma in situ [DCIS]) also was a strong predictor. Tumor size was significant only for the larger volume group (P = 0.029). On multivariate analysis, only histology and initial margin status were significant correlates with residual disease. The adjusted odds ratio for residual disease with pure DCIS was 0.79, and the adjusted odds ratio for invasive ductal or lobular carcinoma (IDC/ILC) without EIC was 0.44 relative to IDC/ILC with EIC (P = 0.008). The adjusted odds ratio for residual disease with a positive initial margin versus a negative initial margin was 2.65 (P < or = 0.0001).

CONCLUSIONS: For excisions amenable to use of the MammoSite catheter, a margin > or = 1.0 mm appeared to afford at most a 35% risk of microscopically detectable residual tumor. Evidence of EIC on excision of IDC/ILC connoted a significantly higher risk. Age did not appear to be predictive for residual disease.}, } @article {pmid16043406, year = {2005}, author = {Mocelin, AO and Issa, VS and Bacal, F and Guimarães, GV and Cunha, E and Bocchi, EA}, title = {The influence of aetiology on inflammatory and neurohumoral activation in patients with severe heart failure: a prospective study comparing Chagas' heart disease and idiopathic dilated cardiomyopathy.}, journal = {European journal of heart failure}, volume = {7}, number = {5}, pages = {869-873}, doi = {10.1016/j.ejheart.2004.10.014}, pmid = {16043406}, issn = {1388-9842}, mesh = {Adult ; Cardiomyopathy, Dilated/*blood/mortality/physiopathology ; Chagas Cardiomyopathy/*blood/mortality/physiopathology ; Female ; Humans ; Interleukin-6/*blood ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Neurotransmitter Agents/blood ; Prospective Studies ; Receptors, Tumor Necrosis Factor/*blood ; Survival Analysis ; Tumor Necrosis Factor-alpha/*analysis ; fas Receptor/*blood ; }, abstract = {Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.}, } @article {pmid16040901, year = {2005}, author = {Birdwell, RL and Bandodkar, P and Ikeda, DM}, title = {Computer-aided detection with screening mammography in a university hospital setting.}, journal = {Radiology}, volume = {236}, number = {2}, pages = {451-457}, doi = {10.1148/radiol.2362040864}, pmid = {16040901}, issn = {0033-8419}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging ; Female ; Hospitals, University ; Humans ; *Mammography/methods ; Middle Aged ; Prospective Studies ; *Radiographic Image Interpretation, Computer-Assisted ; }, abstract = {PURPOSE: To prospectively assess the effect of computer-aided detection (CAD) on screening mammogram interpretation in an academic medical center to determine if the outcome is different than that previously reported for community practices.

MATERIALS AND METHODS: Institutional review board approval was granted, and informed consent was waived. During a 19-month period, 8682 women (median age, 54 years; range, 33-95 years) underwent screening mammography. Each mammogram was interpreted by one of seven radiologists, followed by immediate re-evaluation of the mammogram with CAD information. Each recalled case was classified as follows: radiologist perceived the finding and CAD marked it, radiologist perceived the finding and CAD did not mark it, or CAD prompted the radiologist to perceive the finding and recall the patient. Lesion type was also recorded. Recalled patients were tracked to determine the effect of CAD on recall and biopsy recommendation rates, positive predictive value (PPV) of biopsy, and cancer detection rate. A 95% confidence interval was calculated for cancer detection rate. Pathologic examination was performed for all cancers.

RESULTS: Of 8682 patients, 863 (9.9%) with 960 findings were recalled for further work-up (Breast Imaging Reporting and Data System category 0). After further diagnostic imaging, it was recommended that biopsy or aspiration be performed for 181 of 960 findings (19%); 165 interventions were confirmed to have been performed. Twenty-nine cancers were found in this group, with a PPV for biopsy of 18% (29 of 165 findings) and a cancer detection rate of 3.3 per 1000 screening mammograms (29 of 8682 patients). CAD-prompted recalls contributed 8% (73 of 960 findings) of total recalled findings and 7% (two of 29 lesions) of cancers detected. Of 29 cancers (59%), 17 manifested as masses and 12 (41%) were microcalcifications. Ten (34%) cancers were ductal carcinoma in situ, and the remaining cancers had an invasive component. Both cancers found with CAD manifested as masses, and both were invasive ductal carcinoma.

CONCLUSION: Prospective clinical use of CAD in a university hospital setting resulted in a 7.4% increase (from 27 to 29) in cancers detected. Both cancers were nonpalpable masses.}, } @article {pmid16037890, year = {2005}, author = {Alberty, M and Sidney, M and Huot-Marchand, F and Hespel, JM and Pelayo, P}, title = {Intracyclic velocity variations and arm coordination during exhaustive exercise in front crawl stroke.}, journal = {International journal of sports medicine}, volume = {26}, number = {6}, pages = {471-475}, doi = {10.1055/s-2004-821110}, pmid = {16037890}, issn = {0172-4622}, mesh = {Adult ; Arm/*physiology ; Exercise/*physiology ; Female ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption/physiology ; Physical Endurance/*physiology ; Psychomotor Performance/physiology ; Swimming/*physiology ; *Task Performance and Analysis ; }, abstract = {The purpose of this study was to analyse the effects of an exhaustive exercise on arm coordination and intracyclic velocity variations (IVV) to better understand the ways in which they are modified under fatigue conditions. Seventeen competitive swimmers performed a 200-m all-out test and a set of two 25-m (before and after the 200-m) at maximal intensity to measure stroking parameters, IVV, and the relative duration of the different parts of the stroke cycle and identify the model of arm coordination by using the index of coordination (IdC). Results showed an increase in the relative duration of the propulsive time, which induced a change in arm coordination as fatigue developed in relation to a decrease in stroke length (SL) and stroke rate (SR) (p<0.05). The evolution of IdC corresponds to a reduction of the non-propulsive lag time between the two arms' propulsive actions. Despite these modifications, IVV were not significantly modified (p<0.05). The present results highlighted that IdC and relative durations of each part of the cycle (particularly the pull phase) could be assessed to complete the "SL x SR" model and to partly understand the technique modifications under fatigue condition.}, } @article {pmid16037526, year = {2005}, author = {Oken, SM and Mercado, CL and Memeo, L and Hibshoosh, H}, title = {Invasive ductal carcinoma with fibrotic focus: mammographic and sonographic findings with histopathologic correlation.}, journal = {AJR. American journal of roentgenology}, volume = {185}, number = {2}, pages = {490-494}, doi = {10.2214/ajr.185.2.01850490}, pmid = {16037526}, issn = {0361-803X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Female ; Humans ; Mammography ; Middle Aged ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: We sought to define the imaging findings of invasive ductal carcinoma with fibrotic focus and its associated histopathologic correlation.

CONCLUSION: Radiologists should be aware of the imaging characteristics of this newly described entity because of the significant prognostic implications and perhaps to prompt the pathologist to assess for the presence of a fibrotic focus at excision.}, } @article {pmid16033096, year = {2005}, author = {Shabani, N and Mylonas, I and Kunert-Keil, C and Briese, V and Janni, W and Gerber, B and Friese, K and Jeschke, U}, title = {Expression of glycodelin in human breast cancer: immunohistochemical analysis in mammary carcinoma in situ, invasive carcinomas and their lymph node metastases.}, journal = {Anticancer research}, volume = {25}, number = {3A}, pages = {1761-1764}, pmid = {16033096}, issn = {0250-7005}, mesh = {Breast Neoplasms/*metabolism/pathology ; Glycodelin ; Glycoproteins/*metabolism ; Humans ; Immunohistochemistry ; *Lymphatic Metastasis ; *Neoplasm Invasiveness ; Pregnancy Proteins/*metabolism ; }, abstract = {OBJECTIVE: Glycodelin is a 28 kDa glycoprotein, previously known as placental protein 14 (PP 14). Glycodelin displays immunosuppressive and contraceptive properties. It also suppresses the cytolytic capacity of human natural killer (NK) cells in vitro and inhibits binding of sperm cells to the zona pellucida (the outer membrane of the oocyte). Glycodelin is expressed in normal glandular epithelium of the endometrium as well as in endometrial, ovarian and cervical carcinoma cells. Glycodelin is also expressed in normal and malignant glandular cells outside the reproductive tract, like hidroadenoma, parabronchial glands, sweat glands and pancreatic cystadenoma. Recently, glycodelin was demonstrated to be expressed in normal and cancerous human breast tissue.

MATERIALS AND METHODS: Paraffin-embedded slides of carcinoma in situ (8 DCIS, 2 CLIS), invasive carcinomas without lymph node metastases (9 invasive duct carcinomas, 1 invasive lobular carcinoma) and invasive carcinomas (7 invasive duct carcinomas, 2 invasive lobular carcinomas, 1 mucinous carcinoma) with corresponding lymph node metastases were used. Immunohistochemical staining reaction was used to detect glycodelin expression in the different types of carcinoma in situ, in invasive carcinoma of the human breast and in metastatic carcinoma in axillary lymph nodes.

RESULTS: Glycodelin expression was found in all cases of carcinoma in situ (10/10). In the group of invasive carcinoma of the breast (ductal and lobular carcinoma) without lymph node metastases, expression of glycodelin was demonstrated in 9 cases (9/10), of whom 3 cases showed a strong and 6 cases a mediate to weak expression of glycodelin. Only 1 case was negative. In the group of invasive breast cancer with axillary lymph node metastases, in 5 cases (4 ductal and 1 lobular carcinoma) there was no expression of glycodelin, either in the primary tumour tissue, or in the metastatic infiltration of the axillary lymph nodes (5/10). In only one case (invasive ductal carcinoma) was there a strong expression of glycodelin in the primary tumour and a weak expression in the metastasis in axillary lymph node. In 4 other cases (2 ductal, 1 lobular and 1 mucinous), there was a weak staining in primary breast cancer cells and no expression in the metastatic lymph node.

CONCLUSION: These results demonstrate that invasive breast carcinomas without axillary lymph node metastases (better prognosis) are more likely to express glycodelin. In contrast, the cases of breast cancer with metastatic infiltration of the axillary lymph nodes showed no (or weak) expression of glycodelin (worse prognosis). On the basis of these results, we speculate that glycodelin expression could be used as a prognostic marker for breast cancer. This has to be confirmed in larger studies.}, } @article {pmid16033090, year = {2005}, author = {Mylonas, I and Makovitzky, J and Jeschke, U and Briese, V and Friese, K and Gerber, B}, title = {Expression of Her2/neu, steroid receptors (ER and PR), Ki67 and p53 in invasive mammary ductal carcinoma associated with ductal carcinoma In Situ (DCIS) Versus invasive breast cancer alone.}, journal = {Anticancer research}, volume = {25}, number = {3A}, pages = {1719-1723}, pmid = {16033090}, issn = {0250-7005}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal/*metabolism/pathology ; Female ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Neoplasm Invasiveness ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {AIMS: (a) To assess the expression patterns of HER2/neu, steroid receptors (ER and PR), Ki67 and p53 in invasive ductal cancer (IDC) and IDC associated with carcinoma in situ (IDC/DCIS) and (b) to determine if there is a differential expression of these molecular markers between IDC and IDC/DCIS.

MATERIALS AND METHODS: Paraffin-fixed breast cancer samples, diagnosed with only one histological invasive tumor (IDC (n=130), and IDC/DCIS (n=36) were analyzed by immunohistochemical means. The non-parametric Mann-Whitney and chi2 tests were used to evaluate any statistical differences between different groups. Significance was assumed at p<0.05.

RESULTS: A significant increase of the tumor grading was observed between IDC and IDC/DCIS (p<0.05). Her2/neu amplification was demonstrated in 49.6% of IDC compared to 31% of IDC/DCIS (p<0.05). ER expression showed no statistical differences between IDC and IDC/DCIS. The PR expression was demonstrated in 71% of IDC with significantly lower intensity than IDC/DCIS (p<0.05). The Ki67 expression was significantly higher (p<0.05) in IDC cases (64%) versus IDC/DCIS (49.7%). No differences were observed between IDC and IDC/DCIS for p53 expression.

CONCLUSION: We demonstrated significantly different expression patterns of Her2/neu, PR and Ki67 in IDC versus IDC/DCIS. Since these molecular markers play important roles in carcinogenesis and tumor progression, IDC/DCIS could be an important subtype of mammary invasive ductal cancer. Differences in expression of the evaluated markers might suggest a higher malignant potential of invasive carcinomas alone. The lower expression of Her2/neu and Ki67 in IDC/DCIS could implicate a less malignant behavior compared to a differentiated IDC. Additionally, these results might suggest that DCIS might be a malignant preform and the interaction with neoplastic tissue could result in an aggressive type of invasive tumor.}, } @article {pmid16024247, year = {2005}, author = {Sasano, H and Anderson, TJ and Silverberg, SG and Santen, RJ and Conway, M and Edwards, DP and Krause, A and Bhatnagar, AS and Evans, DB and Miller, WR}, title = {The validation of new aromatase monoclonal antibodies for immunohistochemistry--a correlation with biochemical activities in 46 cases of breast cancer.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {95}, number = {1-5}, pages = {35-39}, doi = {10.1016/j.jsbmb.2005.04.027}, pmid = {16024247}, issn = {0960-0760}, mesh = {*Antibodies, Monoclonal ; Aromatase/*analysis/immunology ; Breast Neoplasms/diagnosis/*enzymology ; Female ; Humans ; *Immunohistochemistry ; }, abstract = {Intratumoral aromatase is a therapeutic target for the treatment of post-menopausal estrogen-dependent breast cancers. Therefore, reliable methods should be developed for routine application for the detection of intratumoral aromatase. Immunohistochemistry (IHC) is considered one of the most suitable methods in this regard. A multi-centre collaborative group has been established to generate and validate new aromatase monoclonal antibodies. We have selected two monoclonal antibodies, #677 against native aromatase protein and F2 against formalin-fixed protein for this purpose. With these two monoclonal antibodies 43 cases of invasive ductal carcinoma, which had been previously assayed for aromatase activity by product isolation methodology, were immunostained in three laboratories in UK, USA and Japan and independently evaluated by three pathologists (H.S., T.A. and S.G.S.). Staining of malignant epithelium, adipose tissue, normal/benign and stromal compartments of the tumors were assessed by estimating the proportion of positive staining cells and the relative intensity of staining in this fashion. Immunoreactivity could be detected in each component of the tissue specimens but a significant positive correlation with biochemical activity was detected only in malignant epithelium stained with 677 not in other components with #677 and not in any of the components. Staining using F2 as a primary antibody did not produce a positive correlation in any components with aromatase activity. These results suggest that we now have a monoclonal antibody against aromatase (#677) which may be used to stain archival materials. A methodology and scoring system is recommended whereby staining significantly correlates with aromatase activity of the resected tissue specimens of breast cancer.}, } @article {pmid16023232, year = {2006}, author = {Tsagalou, EP and Anastasiou-Nana, MI and Terrovitis, JV and Nanas, SN and Alexopoulos, GP and Kanakakis, J and Nanas, JN}, title = {The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease.}, journal = {International journal of cardiology}, volume = {108}, number = {2}, pages = {244-250}, doi = {10.1016/j.ijcard.2005.05.012}, pmid = {16023232}, issn = {0167-5273}, mesh = {Administration, Oral ; Aged ; Amiodarone/administration & dosage/*therapeutic use ; Cardiomyopathy, Dilated/*drug therapy/mortality ; Dobutamine/administration & dosage/*therapeutic use ; Female ; Hemodynamics/drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Myocardial Ischemia/*drug therapy/mortality ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI+amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC).

METHODS: The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h.

RESULTS: There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups. The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P=0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P=0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods.

CONCLUSIONS: Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.}, } @article {pmid16022118, year = {2005}, author = {Lombardi, R and Costantini, M and Romani, M and Belli, P}, title = {Combined diagnostic approach in a breast unit: a case of minimal sign.}, journal = {Rays}, volume = {30}, number = {1}, pages = {31-36}, pmid = {16022118}, issn = {0390-7740}, mesh = {Biopsy, Needle ; Breast/pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Female ; Humans ; Mammography ; Middle Aged ; Ultrasonography, Mammary ; }, abstract = {The case of a 57-year old woman, apparently in good health, in menopause with familial incidence of breast cancer is discussed. The patient came to the Senology Unit for annual control mammography. For diagnostic completion US was performed: it showed the presence of a hypoechoic neoformation highly suggestive of malignancy (class V BI-RADS). Therefore, US-guided needle aspiration biopsy was performed. It confirmed the malignant nature of the neoformation and surgery was planned. At definitive histological examination a small invasive ductal carcinoma, 6 mm in diameter, was diagnosed.}, } @article {pmid16022017, year = {2005}, author = {Hoehne, FM and Taylor, E}, title = {Trends in breast cancer at a county hospital.}, journal = {The American surgeon}, volume = {71}, number = {2}, pages = {159-163}, pmid = {16022017}, issn = {0003-1348}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biopsy/statistics & numerical data ; Breast/pathology ; Breast Neoplasms/*epidemiology ; Breast Self-Examination/statistics & numerical data ; California/epidemiology ; Carcinoma in Situ/epidemiology ; Carcinoma, Ductal, Breast/epidemiology ; Carcinoma, Lobular/epidemiology ; Female ; Hospitals, County/statistics & numerical data ; Hospitals, Teaching/statistics & numerical data ; Humans ; Mammography/statistics & numerical data ; Mass Screening/statistics & numerical data ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; }, abstract = {Breast cancer mortality has changed dramatically with improvements in screening techniques. Mammography is essential for early detection; however, its contribution to the survival benefit in young women is questionable. We report our experience in breast biopsies at a county teaching hospital with a traditionally younger patient population. Institutional review board approval was obtained prior to data collection. A total of 550 breast biopsies were conducted between 1995 and 2000. Data regarding age, method of breast biopsy, and pathology was reviewed. One hundred twenty of 550 patients (21.8%) had breast carcinoma detected on breast biopsies with the predominant histologic subtype being invasive ductal carcinoma. The mean age of patients with carcinoma was 52.8 years, whereas that of patients with benign breast disease was 43.6 years (P < 0.05). Forty-three per cent of all breast cancers occurred in women under the age of 50 years. During the study period, there was neither an increase in the number of breast biopsies performed per year nor a decrease in the average age of women with breast cancer. However, observing a significant percentage of breast cancer patients under 50 years old, our data suggest the importance of strict adherence to current screening recommendations including self-breast examination and yearly mammography.}, } @article {pmid16021542, year = {2005}, author = {Obenauer, S and Sohns, C and Werner, C and Grabbe, E}, title = {[Retrospective analysis of a computer-aided detection (CAD) system in full-field digital mammography in correlation to tumor histology].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {177}, number = {8}, pages = {1103-1109}, doi = {10.1055/s-2005-858321}, pmid = {16021542}, issn = {1438-9029}, mesh = {Adult ; Aged ; *Artificial Intelligence ; Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Radiographic Image Enhancement/*methods ; Radiographic Image Interpretation, Computer-Assisted/*methods ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Statistics as Topic ; }, abstract = {PURPOSE: To evaluate the usefulness of a computer-aided detection (CAD) system in full-field digital mammography in correlation to tumor histology.

MATERIAL AND METHODS: A total of 476 patients (226 patients with histologically proven malignant tumors, 250 healthy women) took part in this study. The mammograms were studied retrospectively, using the CAD system Image Checker. For 226 patients digital mammograms in MLO-projection were available. For 186 of these patients the CC-projection was also available. CAD markers that correlated with histologically proven carcinomas were considered to be true-positive markers. All other CAD markers were considered to be false-positive. Histologically proven carcinomas without markers were false-negative results. The dependence of the CAD markers placement upon the different carcinoma histologies was studied using the Chi-square test.

RESULTS: No significant difference could be proven for the detectability of malignant breast lesions of different histologic types. For the detectability of ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), lobular carcinoma in situ (LCIS), tubular carcinoma and ductulo-lobular carcinoma, the true positives were 71.1 %, 75 %, 70.7 %, 70 %, 60 % and 80 %, respectively, in the MLO projection and 83.9 %, 75.9 %, 81.8 %, 77.8 %, 87.5 % and 33.3 %, respectively, in the CC projection. There was an average of 0.5 false-positive markers per mammographic image.

CONCLUSION: The histologic type of carcinoma seems to have no influence on detectability when using the CAD system. The high rate of false-positive markers shows, however, the limited specificity of the CAD system and that improvements are necessary.}, } @article {pmid16020969, year = {2005}, author = {Tsutsui, S and Inoue, H and Yasuda, K and Suzuki, K and Higashi, H and Era, S and Mori, M}, title = {Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast.}, journal = {Oncology}, volume = {68}, number = {4-6}, pages = {398-404}, doi = {10.1159/000086981}, pmid = {16020969}, issn = {0030-2414}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/metabolism ; *Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases/*metabolism ; Prognosis ; Receptors, Estrogen/metabolism ; Survival Rate ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {OBJECTIVE: The PTEN tumor suppressor gene has been demonstrated to be inactivated in a variety of human tumors. In breast cancer, the PTEN gene mutation is not commonly found whereas loss of heterozygosity affecting the PTEN locus is frequently found. The aim of this study was to analyze PTEN protein expression in breast cancer and to evaluate the prognostic significance of PTEN protein expression.

METHODS: Paraffin-embedded sections ofinvasive ductal carcinoma of the breast were immunohistochemically stained for PTEN protein expression in 236 breast cancers. The immunohistochemical expression of breast cancer cells was judged to be either normal or reduced compared with the PTEN protein expression of the normal mammary gland.

RESULTS: The expression of PTEN protein was found to have decreased in 67 (28%) of 236 breast cancers. The reduced expression correlated with lymph node metastasis (p = 0.0371), but not with tumor size, nuclear grade, MIB-1 counts or p53 protein expression. Univariate analysis indicated that patients with a reduced PTEN expression had a shorter disease-free survival (DFS) than those with a normal PTEN expression (p = 0.0174). Univariate analyses also determined tumor size, lymph node metastases, nuclear grade, MIB-1 counts, p53 protein as well as PTEN protein expression to be significant factors for DFS, while multivariate analysis determined lymph node metastases and the MIB-1 counts to be independent significant factors for DFS.

CONCLUSIONS: The inactivation of PTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers. The reduced expression of PTEN protein correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.}, } @article {pmid16012726, year = {2005}, author = {Tsutsui, S and Yasuda, K and Suzuki, K and Tahara, K and Higashi, H and Era, S}, title = {Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density.}, journal = {Oncology reports}, volume = {14}, number = {2}, pages = {425-431}, pmid = {16012726}, issn = {1021-335X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/metabolism/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Macrophages/*pathology ; Middle Aged ; Multivariate Analysis ; Neovascularization, Pathologic/pathology ; Prognosis ; Vascular Endothelial Growth Factor A/biosynthesis ; }, abstract = {Stromal cells, within and around the tumor, as well as tumor cells are both involved in angiogenesis which is an important step in tumor growth and metastasis. Among such stromal cells, macrophages are known to play various roles in tumor angiogenesis and have thus been called tumor-associated macrophages (TAMs). The TAM density, vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) were immunohistochemically evaluated in 249 paraffin-embedded sections of invasive ductal carcinoma of the breast. The TAM density and MVD were assessed as the average density of three hot spots at a magnification of x400 and x200, respectively. The TAM density showed a significant correlation with both the VEGF expression and MVD, while a significant correlation was also found between the VEGF expression and MVD. The TAM density was also associated with the nuclear grade, estrogen receptor status and MIB-1 count. Patients with a high TAM density had a significantly (p=0.0025) worse disease-free survival (DFS) prognosis than those with a low TAM density, while univariate analyses also indicated both the MVD (p<0.0001) and VEGF expression (p=0.0152) to be prognostic factors for DFS. A multivariate analysis indicated MVD (p=0.0057), as well as lymph node metastasis and the MIB-1 count, to be independently significant prognostic factors for DFS. In conclusion, the present study demonstrated a close association between TAM infiltration and both the VEGF expression and MVD. The prognostic significance of MVD was the strongest among these three factors in breast cancer. These findings suggested that the prognostic implications of TAM infiltration are due to the involvement of TAMs in tumor angiogenesis.}, } @article {pmid16008586, year = {2005}, author = {Edwards, JL and Apicella, MA}, title = {I-domain-containing integrins serve as pilus receptors for Neisseria gonorrhoeae adherence to human epithelial cells.}, journal = {Cellular microbiology}, volume = {7}, number = {8}, pages = {1197-1211}, doi = {10.1111/j.1462-5822.2005.00547.x}, pmid = {16008586}, issn = {1462-5814}, support = {5-T32-AI07511-07/AI/NIAID NIH HHS/United States ; AI45728/AI/NIAID NIH HHS/United States ; }, mesh = {Asialoglycoprotein Receptor/metabolism ; Bacterial Adhesion ; Cells, Cultured ; Epithelial Cells/metabolism/microbiology/*physiology ; Humans ; Immunoprecipitation ; Integrin alpha Chains/*metabolism ; Male ; Neisseria gonorrhoeae/metabolism/*physiology ; Pili, Sex/metabolism/*physiology ; Protein Structure, Tertiary ; Urethra/cytology/*microbiology ; }, abstract = {Two pilus receptors are identified for the pathogenic Neisseria, CD46 and complement receptor 3. An intimate association between the asialoglycoprotein receptor and gonococcal lipooligosaccharide mediates invasion of primary, male urethral epithelial cells (UECs); however, studies to identify pilus receptors on these cells have not been performed. Based on our previous studies we reasoned that the I-domain-containing (IDC), alpha(1)- and alpha(2)-integrins might serve as pilus receptors on UECs and on urethral tissue. Confocal microscopy revealed colocalization of pilus with alpha(1) and alpha(2) integrins on UECs and tissue. We found that recombinant I-domain and antibodies directed against the alpha(1)- and alpha(2)-integrins inhibited gonococcal association with UECs and with immortal cell lines of variable origin. Gonococcus-integrin colocalization occurred at early time points post infection, but this interaction dissociated with extended infection. Similarly, Western Blot analyses revealed that gonococcal pilin coimmunoprecipitates with alpha(1)- and alpha(2)-integrins. However, studies performed in parallel and that were designed to capture CD46-pilus immune complexes indicated that a CD46-pilus interaction did not occur. Collectively, these data suggest that while CD46 might be able to bind gonococcal pilus, IDC integrins are preferentially used as the initial docking site for gonococci on UECs, on urethral tissue and on some immortal cell lines.}, } @article {pmid16007648, year = {2005}, author = {Yokoyama, T and Kawahara, A and Kage, M and Kojiro, M and Takayasu, H and Sato, T}, title = {Image analysis of irregularity of cluster shape in cytological diagnosis of breast tumors: cluster analysis with 2D-fractal dimension.}, journal = {Diagnostic cytopathology}, volume = {33}, number = {2}, pages = {71-77}, doi = {10.1002/dc.20309}, pmid = {16007648}, issn = {8755-1039}, mesh = {Adenofibroma/*pathology ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Cluster Analysis ; Female ; Humans ; Image Processing, Computer-Assisted ; Predictive Value of Tests ; }, abstract = {To establish diagnostic criteria using comparison of cell cluster shapes, between benign and malignant tumors, breast tumors demonstrating weak cellular atypia in low grade invasive ductal carcinoma (IDC) were compared. Fine-needle aspiration (FNA) specimens of breast tumors were obtained from 37 patients. Among these, 16 were histologically diagnosed as IDC low-grade and the other 21 as benign fibroadenoma (FA). For evaluation, we examined 740 clusters from these 37 FNA specimens. Nine image morphometric parameters were studied, including the cluster area, circumference, maximal length, maximal breadth, ratio of length to breadth, cluster roundness, cluster size, and the edge and distribution image fractal dimensions for cluster analysis. We evaluated the irregularity in cell cluster shape using fractal dimension analysis, and determined the correlation to cluster size. The irregularity in the IDC cluster shape was higher than that in the FA cluster shape. However, six cases (28.5%) of 21 FA clusters showed high fractal dimensions similar to those for IDC. The clusters were classified by cluster analysis into three types: IDC clusters, FA with irregular cluster shape, and FA with no irregular clusters. The average cell cluster area of the FA with irregular shape was found to be about three times larger than that of IDC clusters. When the differential diagnosis between IDC and FA is difficult, it is important to focus on irregularities in the shape and on overall size of the cell clusters. For accurate diagnosis, the cell cluster shape is as important as the individual cellular atypia.}, } @article {pmid15999153, year = {2005}, author = {Simsa, P and Teillaud, JL and Stott, DI and Tóth, J and Kotlan, B}, title = {Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.}, journal = {Pathology oncology research : POR}, volume = {11}, number = {2}, pages = {92-97}, pmid = {15999153}, issn = {1219-4956}, mesh = {B-Lymphocytes/*immunology ; Brain Stem Neoplasms/immunology/pathology ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; *Genes, Immunoglobulin ; Humans ; Immunoglobulin Variable Region/*genetics ; Lymphocytes, Tumor-Infiltrating/*immunology ; Neoplasm Invasiveness/*pathology ; Retrospective Studies ; }, abstract = {A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.}, } @article {pmid15998374, year = {2005}, author = {Guler, G and Uner, A and Guler, N and Han, SY and Iliopoulos, D and McCue, P and Huebner, K}, title = {Concordant loss of fragile gene expression early in breast cancer development.}, journal = {Pathology international}, volume = {55}, number = {8}, pages = {471-478}, doi = {10.1111/j.1440-1827.2005.01855.x}, pmid = {15998374}, issn = {1320-5463}, support = {CA53036/CA/NCI NIH HHS/United States ; CA77738/CA/NCI NIH HHS/United States ; }, mesh = {Acid Anhydride Hydrolases/*biosynthesis/genetics ; Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Chi-Square Distribution ; Chromosome Fragile Sites/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*biosynthesis/genetics ; Oxidoreductases/*biosynthesis/genetics ; Receptor, ErbB-2/analysis ; Tumor Suppressor Protein p53/analysis ; Tumor Suppressor Proteins ; WW Domain-Containing Oxidoreductase ; }, abstract = {The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression has been reported in approximately two-thirds of invasive breast tumors. Expression of these fragile gene products, as well as ErbB2 and p53, were evaluated immunohistochemically in 44 pure and 31 adjacent-to-invasive ductal carcinoma in-situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent-to-invasive tumor cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases. Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in the DCIS adjacent-to-invasive group. Reduced Fhit and Wwox expression was observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS adjacent-to-invasive lesions, Fhit and Wwox expression was positively associated (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component there was a positive trend toward association (P = 0.075). Fhit and Wwox were more frequently reduced in high-grade lesions in the DCIS adjacent-to-invasive (P = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a statistically significant negative association between Fhit and ErbB2 expression in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in-situ breast cancer was associated, which may contribute to the high-grade DCIS-invasive tumor pathway.}, } @article {pmid15996865, year = {2006}, author = {Yamaguchi, H and Ishikawa, M and Hatanaka, K and Uekusa, T and Ishimaru, M and Nagawa, H}, title = {Occult breast cancer presenting as axillary metastases.}, journal = {Breast (Edinburgh, Scotland)}, volume = {15}, number = {2}, pages = {259-262}, doi = {10.1016/j.breast.2005.04.018}, pmid = {15996865}, issn = {0960-9776}, mesh = {Axilla ; Breast Neoplasms/*diagnosis/secondary ; Carcinoma, Ductal, Breast/*diagnosis/secondary ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Unknown Primary/*diagnosis/pathology ; }, abstract = {We report the case of a 52-year-old woman with occult breast cancer who presented with a hard metastatic nodule in the left axilla. Although histology identified a metastatic adenocarcinoma in the lymph nodes, numerous tests failed to detect the primary tumor. Immunohistochemistry showed that the resected lymph node was positive for both estrogen and progesterone receptors, suggesting the breast as the site of the primary tumor. Left modified radical mastectomy was performed. Pathology revealed an invasive ductal carcinoma (1.5x1 mm in size) with extensive lymphatic involvement, which strongly expressed both vascular endothelial growth factor-C (VEGF-C) and VEGF-D.}, } @article {pmid15996167, year = {2005}, author = {Liu, W and Li, WM and Sun, NL}, title = {HLA-DQA1, -DQB1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy in Hans of northern China.}, journal = {Annals of human genetics}, volume = {69}, number = {Pt 4}, pages = {382-388}, doi = {10.1111/j.1529-8817.2005.00166.x}, pmid = {15996167}, issn = {0003-4800}, mesh = {Adult ; Alleles ; Asian People/genetics ; Cardiomyopathy, Dilated/epidemiology/*genetics/immunology ; Case-Control Studies ; China/epidemiology ; Female ; *Genetic Predisposition to Disease ; Genotype ; HLA-DQ Antigens/*genetics/immunology ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Humans ; Lod Score ; Male ; *Polymorphism, Genetic ; }, abstract = {Autoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex (MHC) may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, especially HLA-DQ genes, which are highly polymorphic, play an important role in the activation of immune responses and thus control the predisposition to, or protection from, IDC. This study was conducted to investigate the association of HLA-DQA1, -DQB1 allele polymorphisms with an autoantibody against the myocardial mitochondria ADP/ATP carrier, and to explore susceptibility to idiopathic dilated cardiomyopathy (IDC) among the Han ethnic group in northern China and the immunological mechanisms and hereditary susceptibility to IDC. Polymerase chain reaction sequence-specific primer (PCR-SSP) techniques were used to analyze polymorphisms of the second exon of HLA-DQA1 and -DQB1 alleles among 68 unrelated IDC patients, 4 probands of IDC pedigrees, and 100 healthy controls, all of Han nationality and having lived in northern China for a long time. Following echocardiography examination the IDC subjects were stratified according to ejection fraction (EF) values. Those with EF values higher than 50% were placed in subgroup 1, subgroup 2 included the patients with an EF value of 15-35%, and subgroup 3 consisted of those whose EF values were less than 15%. An autoantibody against the myocardial mitochondria ADP/ATP carrier was examined using immunoblot analysis. The frequencies of HLA-DQA1*0501 and HLA-DQB1*0303 were 0.3889 and 0.1806 in the IDC group, significantly higher than those of the healthy controls (0.0900 and 0.0364 respectively, both P < 0.05). The OR was 5.20 (95% CI: 3.60-8.50) and 4.85 (95% CI: 2.56-9.39) respectively. Further analysis of the three subgroups showed a higher frequency of HLA-DQA1*0501 among patients whose EF was less than 15% than those whose EF values were > or =15%. Conversely, the frequencies of HLA-DQA1*0201 and -DQB1*0502, *0504 were significantly lower in the IDC group (0.0139, 0.0139 and 0.0417 respectively) than in the control group (0.2000, 0.0727 and 0.1091 respectively) (P < 0.05). The frequency of the HLA-DQA1*0501 allele was significantly higher in IDC patients whose autoantibody is positive in contrast with those whose autoantibody is negative (18.57% vs. 5.86%, P < 0.05); the relative risk (RR) was 4.32. The other frequencies of HLA-DQA1 and -DQB1 alleles showed no significant difference in the antibody positive and negative groups of IDC patients. The alleles of HLA-DQA1*0501 and HLA-DQB1*0303 were closely associated with poor EF values in the IDC group, and may be involved in susceptibility to the disease. The DQA1*0201 and DQB1*0502, *0504 alleles may confer protection to IDC among individuals of northern Chinese Han nationality. The SER(57) residue in the second exon of DQB1*0502 and *0504 may confer resistance to IDC, and defects or substitution of this amino acid residue at position 57 of the DQbeta chain may be associated with IDC susceptibility. HLA-DQ allele polymorphisms may serve as genetic markers for IDC and be involved in the regulation of the immune specific response to auto or exterior anti-myocardium antibodies.}, } @article {pmid15995634, year = {2005}, author = {Tokatli, F and Altaner, S and Uzal, C and Ture, M and Kocak, Z and Uygun, K and Bilgi, S}, title = {Association of HER-2/neu overexpression with the number of involved axillary lymph nodes in hormone receptor positive breast cancer patients.}, journal = {Experimental oncology}, volume = {27}, number = {2}, pages = {145-149}, pmid = {15995634}, issn = {1812-9269}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/secondary ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*metabolism/pathology ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/*metabolism ; Receptors, Estrogen/metabolism ; Survival Rate ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIM: To evaluate the prognostic significance of HER-2/neu overexpression in hormone receptor and axillary lymph node positive breast cancer patients treated in a single institution.

METHODS: Paraffin-embedded primary breast cancers from 40 patients with invasive ductal carcinoma were studied immunohistochemically. HER-2/neu staining was classified as negative (0, 1+), weak/moderate positive (2+), or moderate/strong positive (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses.

RESULTS: 20% of patients were positive for HER-2/neu. Significant associations were observed between HER-2/neu and increasing number of involved nodes (p = 0.014), p53 positivity (p = 0.039), the presence of vascular invasion (p = 0.029) and metastases (p = 0.01). Multivariate analysis demonstrated that HER-2/neu overexpression (p = 0.016) and age (p = 0.005) were independent predictors for disease-free survival (DFS) where the number of involved nodes (p = 0.032) was shown to be independent predictor for overall survival. In the HER-2/neu positively stained tumors, significant number of patients developed distant metastases than the patients with HER-2/neu negatively stained tumors (87.5% vs 34.4%, p = 0.01).

CONCLUSION: For node positive patients, HER-2/neu overexpression was a significant predictor of DFS.}, } @article {pmid15990453, year = {2005}, author = {Pellegrini, P and Totaro, R and Contasta, I and Berghella, AM and Carolei, A and Adorno, D}, title = {CD30 antigen and multiple sclerosis: CD30, an important costimulatory molecule and marker of a regulatory subpopulation of dendritic cells, is involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. The role of IFNbeta-1a in the treatment of multiple sclerosis.}, journal = {Neuroimmunomodulation}, volume = {12}, number = {4}, pages = {220-234}, doi = {10.1159/000085654}, pmid = {15990453}, issn = {1021-7401}, mesh = {Adult ; Biomarkers/metabolism ; Cytokines/immunology ; Dendritic Cells/drug effects/*immunology ; Down-Regulation/drug effects/immunology ; Female ; Humans ; Immune Tolerance/immunology ; Immunity, Cellular/drug effects/immunology ; Immunologic Factors/*immunology/metabolism ; Interferon beta-1a ; Interferon-beta/pharmacology/therapeutic use ; Ki-1 Antigen/*immunology ; Male ; Multiple Sclerosis/drug therapy/*immunology/physiopathology ; Principal Component Analysis ; Severity of Illness Index ; Th1 Cells/*immunology ; Th2 Cells/*immunology ; }, abstract = {OBJECTIVES: The immunological effect of CD30 on dendritic cells (DCs) was examined in a comparative study of patients with relapsing-remitting multiple sclerosis (RRMS). The patients were divided into two groups on the basis of interferon (IFN)beta-1a treatment: IFNbeta-1a-treated patients and untreated patients. We have already shown that CD30 is a marker of cells involved in the regulation of the balance between TH1 and TH2 immune responses and so the aim of this study was to confirm this role in DCs and, consequently, to clarify the immunopathological mechanisms of MS and the causes of immunosuppressive drug failure.

METHODS: We studied network interactions between soluble (s) CD30 and TH1/TH2 cytokines in the supernatants of CD14+-derived immature DC (IDC) and DC cultures from treated and untreated patients. Network interactions between the sCD30 and cytokines in IDC and DC supernatants were also evaluated in relation to TH1/TH2 cytokine serum levels.

RESULTS: Our overall results show that CD30 is expressed on IDCs and DCs, indicating an immunological role in resting and activated physiological conditions. This role would appear to be the regulation of the resting and activated physiological balance between the TH1/TH2 immune functions as abnormal increases in sCD30 levels result in impaired regulation. Further studies are undoubtedly required to clarify this situation. IFNbeta-1a treatment was found to determine a fall in sCD30 levels, leading to the restoration of the normal functional selection of IDCs from progenitor cells and the regulation of the TH1/TH2 network balance. However, IFNbeta-1a treatment may also be responsible for the in vivo suppression of CD30-mediated TH1-DC functions in immune activation. TH1-DC functions are involved in the induction of T-regulatory cells for the physiological deletion of self-aggressive cells.

CONCLUSION: We conclude that CD30 is an important costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells involved in the maintenance of the physiological balance between TH1/TH2 immune responses and tolerance. Elucidating the mechanisms restoring DC and T-regulatory cell function could lead to more effective therapy and strategies for the prevention and treatment of immunopathological conditions such as autoimmunity, transplant rejection, allergy and tumors.}, } @article {pmid15986450, year = {2005}, author = {Kasper, G and Weiser, AA and Rump, A and Sparbier, K and Dahl, E and Hartmann, A and Wild, P and Schwidetzky, U and Castaños-Vélez, E and Lehmann, K}, title = {Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.}, journal = {International journal of cancer}, volume = {117}, number = {6}, pages = {961-973}, doi = {10.1002/ijc.21235}, pmid = {15986450}, issn = {0020-7136}, mesh = {Base Sequence ; Breast Neoplasms/chemistry/*genetics/pathology ; Cation Transport Proteins/analysis/*genetics ; DNA, Complementary/chemistry ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Endoplasmic Reticulum/chemistry ; *Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Middle Aged ; Molecular Sequence Data ; Neoplasm Proteins/analysis/*genetics ; Neoplasm Recurrence, Local ; Prognosis ; RNA, Messenger/analysis ; Receptors, Estrogen/analysis ; Survival Rate ; Tamoxifen ; }, abstract = {We investigated the expression pattern of the breast cancer associated gene LIV-1 on mRNA and protein level in 111 human breast cancer patients by in situ hybridization as well as immunohistochemistry and focused on the unknown potential of LIV-1 expression levels as a prognostic marker. To our knowledge, this is the first study on endogenous LIV-1 protein expression. Results of our study indicate that LIV-1 mRNA and protein expression levels are only weakly correlated, suggesting posttranscriptional regulatory mechanisms. Furthermore, LIV-1 mRNA quantity in combination with a positive ER status seem to represent a better marker than the progesterone receptor status according to the prognostic significance for relapse free survival (RFS). A negative correlation of LIV-1 protein levels with tumor size, grade and stage reflects an association of LIV-1 protein expression with less aggressive tumors. High LIV-1 protein expression seems to be associated with a longer relapse free and overall survival in breast cancer patients with invasive ductal carcinoma. This association, however, seems to be dependent from other prognostic markers. Our data suggest that LIV-1 is a promising candidate for a novel marker for breast cancer patients with better outcome. Furthermore, our study presents a revised cDNA sequence of LIV-1 and demonstrates the localization of endogenous LIV-1 in the endoplasmic reticulum.}, } @article {pmid15983632, year = {2005}, author = {Rossini, M and Piscitelli, P and Fitto, F and Camboa, P and Angeli, A and Guida, G and Adami, S}, title = {[Incidence and socioeconomic burden of hip fractures in Italy].}, journal = {Reumatismo}, volume = {57}, number = {2}, pages = {97-102}, doi = {10.4081/reumatismo.2005.97}, pmid = {15983632}, issn = {0048-7449}, mesh = {Aged ; Arthroplasty, Replacement, Hip/economics ; Diagnosis-Related Groups ; Female ; Femoral Fractures/economics/*epidemiology/rehabilitation/surgery ; Fractures, Spontaneous/economics/epidemiology/etiology/rehabilitation/surgery ; Health Expenditures/statistics & numerical data ; Hip Fractures/economics/*epidemiology/rehabilitation/surgery ; Hospitalization/economics/statistics & numerical data ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; National Health Programs/economics ; Orthopedic Procedures/economics ; Osteoporosis/complications/economics ; Rehabilitation/economics ; Sick Leave/economics ; }, abstract = {OBJECTIVES: The aim of this study was to evaluate the trend of the incidence and costs of hip fractures in Italy.

METHODS: The incidence of hip fractures after 45 years of age in both females and males during the years 1999-2002 was obtained by analyzing the Italian Ministry of Health national hospitalization database, according to the diagnosis codes of International Classification of Diseases, Clinical Modification, 9th edition (IDC-9-CM) that indicate femoral fracture. We have computed all direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRG) referring to hip fractures. The expenses of rehabilitation and indirect expenses were based on estimates.

RESULTS: In 2002, more than 86,000 hip fractures were registered in Italy in male and female patients over 45 years old, with 9% progression compared to 1999; 77% were female and 80% were over 75 years of age. In 2002 the direct costs of hospitalization, in the patients over 65 years alone, were almost 400 million euros, with an increase of 15% as compared to 1999. Considering also estimated rehabilitation costs, social aid and indirect costs, we estimate that hip fractures due to age-related osteoporosis created over a billion euros in expenses in 2002.

CONCLUSIONS: Preventive intervention regarding the risk of hip fracture in elderly patients is urgent.}, } @article {pmid15979827, year = {2005}, author = {Gallardo, S and Cárdaba, B and Posada, M and del Pozo, V and Messeguer, A and David, CS and Lahoz, C}, title = {Toxic oil syndrome: genetic restriction and immunomodulatory effects due to adulterated oils in a model of HLA transgenic mice.}, journal = {Toxicology letters}, volume = {159}, number = {2}, pages = {173-181}, doi = {10.1016/j.toxlet.2005.05.009}, pmid = {15979827}, issn = {0378-4274}, support = {AI-14764/AI/NIAID NIH HHS/United States ; }, mesh = {Aniline Compounds/*toxicity ; Animals ; Eosinophils/*drug effects/immunology ; Fatty Acids, Monounsaturated ; Female ; *Genetic Predisposition to Disease ; Histocompatibility Antigens Class II/genetics ; Humans ; Immunoglobulin E/blood ; Interleukin-4/biosynthesis ; Interleukin-5/biosynthesis ; Lung/drug effects/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Plant Oils/*toxicity ; Propylene Glycols/toxicity ; RNA, Messenger/biosynthesis ; Rapeseed Oil ; Syndrome ; Th2 Cells/*drug effects/immunology ; }, abstract = {Toxic oil syndrome (TOS) was described in Spain in 1981, due to the ingestion of contaminated rapeseed oil denatured with 2% aniline. More than 20,000 persons were affected, causing over 2500 deaths. Immunological findings were: eosinophilia, mRNA for Th2 cytokines (IL-4 and IL-5) in lungs, elevated total IgE and sIL-2R and increase of DR2 HLA class II phenotypic frequency in patients died by TOS. Our objective is to test the genetic restriction found in humans using HLA transgenic mice. Results show that mice expressing human DR2 and DQ6 (both in linkage disequilibrium), had higher percentage of eosinophils (DQ6) and IgE (DR2) than other transgenic mice tested (DR3 and DR4). Also, a Th2 shift was found in DR2 transgenic mice when toxic oil was administered with OVA. This has been corroborated by the IL-5 mRNA expression in 4 out of 6 lung tissues from TOS oil treated BALB/c mice. These data indicate that an immunological response was induced as consequence of the toxic administration. These results correlate with those found in TOS patients and reinforce the implication of genetic restrictions in the acquisition of toxic-mediated disease.}, } @article {pmid15973138, year = {2005}, author = {Pfleiderer, SO and Marx, C and Vagner, J and Franke, RP and Reichenbach, JR and Kaiser, WA}, title = {Magnetic resonance-guided large-core breast biopsy inside a 1.5-T magnetic resonance scanner using an automatic system: in vitro experiments and preliminary clinical experience in four patients.}, journal = {Investigative radiology}, volume = {40}, number = {7}, pages = {458-463}, doi = {10.1097/01.rli.0000167423.27180.54}, pmid = {15973138}, issn = {0020-9996}, mesh = {Biopsy, Needle/instrumentation/*methods ; Breast/*pathology ; Breast Neoplasms/diagnosis/*pathology ; Feasibility Studies ; Female ; Humans ; In Vitro Techniques ; *Magnetic Resonance Imaging ; Middle Aged ; Robotics/*instrumentation ; Sensitivity and Specificity ; }, abstract = {RATIONALE AND OBJECTIVE: The aim of this study was to investigate the feasibility and the precision of magnetic resonance (MR)-guided large-core breast biopsies (LCBB) by using the second prototype of an automatic system (ROBITOM II), which is used to localize lesions while operating at the isocenter of a 1.5-T whole-body scanner.

METHODS AND MATERIALS: In comparison to the first prototype, ROBITOM II is equipped with a dedicated double breast coil and a high-speed trocar setting unit. In vitro experiments (n = 25) with grapefruit phantoms, which contained multiple vitamin E capsules (12 x 7 mm in size) as artificial lesions, were performed. Four patients with MR-detectable breast lesions underwent biopsy. A trocar was positioned in front of the lesion and inserted into the breast. Specimens were harvested with a coaxial technique by using a 14-G core needle biopsy gun.

RESULTS: In all 25 in vitro experiments, capsule material was detected in the specimen cylinder. In 4 patients, the coaxial needle was detected exactly at the expected position. Between 8 and 16 tissue cylinders were harvested. Histologic evaluation resulted in 1 invasive ductal carcinoma and 1 papilloma, which were confirmed after open surgery. One patient who had a proven breast cancer was biopsied for exclusion of multifocal disease. She showed fibrocystic changes, whereas open surgery revealed 3 small areas of ductal carcinoma in situ (DCIS). Another patient showed fibroadenoma after biopsy. This patient is in the follow-up period, which has lasted between 3 and 4 months up until now.

CONCLUSIONS: In this pilot patient study, the feasibility of manipulator-assisted large-core breast biopsy inside a 1.5-T whole-body scanner was demonstrated by using ROBITOM II. The precision of the device was confirmed with in vitro experiments. Although these findings are preliminary and the follow-up period is rather short, they nevertheless represent a successful proof-of-principle of LCBB with ROBITOM II.}, } @article {pmid15971199, year = {2005}, author = {Furman-Haran, E and Schechtman, E and Kelcz, F and Kirshenbaum, K and Degani, H}, title = {Magnetic resonance imaging reveals functional diversity of the vasculature in benign and malignant breast lesions.}, journal = {Cancer}, volume = {104}, number = {4}, pages = {708-718}, doi = {10.1002/cncr.21225}, pmid = {15971199}, issn = {0008-543X}, mesh = {Breast Neoplasms/*blood supply/*diagnostic imaging ; Carcinoma, Ductal, Breast/*blood supply/*diagnostic imaging ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Neovascularization, Pathologic/*diagnostic imaging ; Radiography ; Retrospective Studies ; }, abstract = {BACKGROUND: Tumor perfusion through the microvascular network can be imaged noninvasively by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The objective of the current study was to quantify the microvascular perfusion parameters in various human breast lesions and to determine whether they varied between benign lesions and malignancy and whether they were altered with increased invasiveness.

METHODS: Perfusion parameters in 22 benign fibrocystic changes, 15 ductal carcinomas in situ (DCIS), 30 infiltrating ductal carcinomas (IDC), and 22 fibroadenomas were measured using high-resolution DCE-MRI. Pixel-by-pixel image analysis yielded parametric images of two perfusion indicators: the influx transcapillary transfer constant (k(trans)) and the efflux transcapillary rate constant (k(ep)). Correlations of lesion type and perfusion parameters were calculated using Spearman correlation. Logistic regression analysis evaluated the best predictors of the kinetic parameters that differentiate between IDC and benign lesions.

RESULTS: The perfusion parameters exhibited a progressive increase from benign fibrocystic changes to DCIS and IDC, with a significant correlation between lesion type and the parameters' values (range of correlation coefficients, 0.56-0.76; P < 0.0001). In addition, k(trans) increased from low-grade DCIS to high-grade DCIS. Fibroadenomas were characterized uniquely by high k(trans) but low k(ep). Stepwise logistic regression selected k(trans) as the best predictor for distinguishing benign fibrocystic changes from IDC, yielding 93% sensitivity and 96% specificity.

CONCLUSIONS: The microvascular perfusion parameters in breast lesions were elevated with invasiveness. Quantification of these parameters using high-resolution DCE-MRI was helpful for differentiating between breast lesions and should improve breast carcinoma diagnosis.}, } @article {pmid15964648, year = {2005}, author = {Seifert, L and Chollet, D and Allard, P}, title = {Arm coordination symmetry and breathing effect in front crawl.}, journal = {Human movement science}, volume = {24}, number = {2}, pages = {234-256}, doi = {10.1016/j.humov.2005.05.003}, pmid = {15964648}, issn = {0167-9457}, mesh = {Acceleration ; Adolescent ; Adult ; Competitive Behavior ; *Functional Laterality ; Humans ; Male ; *Motor Skills ; *Psychomotor Performance ; *Respiration ; *Swimming ; }, abstract = {This study analysed the relationships among arm coordination symmetry, motor laterality and breathing laterality during a 100-m front crawl, as a function of expertise. Ten elite swimmers (G1), 10 mid-level swimmers (G2), and 8 non-expert swimmers (G3) composed three skill groups, which were distinguished by velocity, stroke rate, stroke length, breathing frequency (BF) and the mean number of strokes between two breaths - the stroke breath (SB) - over a 100-m front crawl. Four stroke phases were identified by video analysis (catch, pull, push and recovery) and the index of coordination (IdC) measured the lag time between the propulsive phases of the two arms. The three modes of coordination are catch-up (IdC<0%), opposition (IdC=0%) and superposition (IdC>0%). The IdC was established as the mean of IdC1 and IdC2, which measured the lag time between the propulsive phases of the left and right arms, respectively. The coordination symmetry was analysed by comparing IdC1 and IdC2, and the breathing effect was studied by distinguishing IdC1 (and IdC2) with and without breathing. Motor laterality was determined by an adaptation of the Edinburgh Handedness Inventory. Breathing laterality was determined by a questionnaire and observation during the 100-m trial. Most of the front crawl swimmers showed asymmetric arm coordination, with propulsive discontinuity on one side and propulsive superposition on the other. This asymmetry was most often related to breathing laterality (a preferential breathing side for a unilateral breathing pattern) and motor laterality (arm dominance), with different profiles noted. More than the breathing laterality itself, the breathing actions of the non-expert swimmers amplified their asymmetric coordination on the breathing side. Conversely, the elite swimmers, who had higher and more stable spatial-temporal parameters (velocity and stroke lengths), a high coordination value (IdC) and lower breathing frequency (BF), managed their race better than the less proficient swimmers and their asymmetric arm coordination was not disturbed by breathing actions. By determining the dominant arm and the preferential breathing side, the coach can obtain a swimmer profile that allows both coach and swimmer to better understand and respond to excessive coordination asymmetry.}, } @article {pmid15958055, year = {2005}, author = {Tsuda, H and Tani, Y and Weisenberger, J and Kitada, S and Hasegawa, T and Murata, T and Tamai, S and Hirohashi, S and Matsubara, O and Natori, T}, title = {Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated-type breast carcinomas with 'stem-cell-like' features.}, journal = {Cancer science}, volume = {96}, number = {6}, pages = {333-339}, doi = {10.1111/j.1349-7006.2005.00060.x}, pmid = {15958055}, issn = {1347-9032}, mesh = {Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma/*genetics/*pathology ; Carcinoma, Ductal/*genetics/*pathology ; Cell Differentiation ; ErbB Receptors/*biosynthesis/genetics ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-kit/*biosynthesis/genetics ; Receptor, ErbB-2/biosynthesis ; *Stem Cells ; }, abstract = {It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.}, } @article {pmid15944938, year = {2005}, author = {Yu, Z and Sun, J and Zhen, J and Zhang, Q and Yang, Q}, title = {Thymidylate synthase predicts for clinical outcome in invasive breast cancer.}, journal = {Histology and histopathology}, volume = {20}, number = {3}, pages = {871-878}, doi = {10.14670/HH-20.871}, pmid = {15944938}, issn = {0213-3911}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/enzymology/pathology ; Carcinoma, Ductal, Breast/*drug therapy/enzymology/pathology ; Dihydrouracil Dehydrogenase (NADP)/metabolism ; Female ; Fluorouracil/administration & dosage ; Humans ; Immunohistochemistry ; Middle Aged ; Multivariate Analysis ; Prognosis ; Survival Analysis ; Thymidylate Synthase/*metabolism ; Treatment Outcome ; }, abstract = {Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the degradation of 5-FU. Whether TS or DPD could be used as valuable parameters for 5-FU sensitivity in clinical patients are largely unknown. We analyzed TS and DPD expression in breast carcinomas to evaluate the clinicopathological significance of these enzymes in patients with invasive breast cancer receiving 5-FU-based chemotherapy. A total of 197 patients with invasive ductal carcinoma were included in our study. Both the TS and DPD expression were analyzed using immunohistochemical method for all the surgical samples. Sixty-three out of 197 (31.97%) patients are positive for TS expression, and 77 out of 197 (39.09%) patients are positive for DPD expression. TS expression was not correlated with DPD expression. Patients with TS-positivity had aggressive phenotype including large tumor size, low differentiation and nodal metastasis. DPD expression is not related with phenotype or prognosis. Multivariate analysis demonstrated that TS expression was an independent prognostic factor for both disease-free and overall survival. The current study demonstrated that TS but not DPD expression was associated with both progression and prognosis in breast cancer receiving 5-FU-based chemotherapy. TS expression in the primary tumor might be useful as a predictive parameter for the efficacy of 5-FU-based chemotherapy for breast cancer.}, } @article {pmid15944918, year = {2005}, author = {Kuroda, N and Jin, YL and Hamauzu, T and Toi, M and Miyazaki, E and Hiroi, M and Moriki, T and Enzan, H}, title = {Consistent lack of CD34-positive stromal cells in the stroma of malignant breast lesions.}, journal = {Histology and histopathology}, volume = {20}, number = {3}, pages = {707-712}, doi = {10.14670/HH-20.707}, pmid = {15944918}, issn = {0213-3911}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/*analysis ; Breast/chemistry/*pathology ; Breast Neoplasms/metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Female ; Fibroadenoma/metabolism/pathology ; Fibrocystic Breast Disease/metabolism/pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Stromal Cells/chemistry/pathology ; }, abstract = {To examine the distribution of CD34-positive and ASMA-positive stromal cells in various breast lesions, we performed immunohistochemical assays (using a streptavidin-biotin immunoperoxidase technique) of tissue specimens, obtained by excisional biopsy and partial or total mastectomy, from 62 patients with breast lesions. Specimens were obtained from 64 lesions as follows: fibrocystic disease (n=12), intraductal papilloma (n=4), fibroadenoma (n=17), invasive lobular carcinoma (n=6), invasive ductal carcinoma (n=20) and invasive micropapillary carcinoma (n=5). In normal breast tissue (controls), CD34-positive spindle cells were abundant in the intralobular stroma, but no ASMA-positive stromal cells were identified except myoepithelial cells. Small to large numbers of CD34-positive cells were observed in the stroma of 29 of 33 benign diseases. In all invasive carcinomas (lobular, ductal and micropapillary), no CD34-positive stromal cells were observed in the stroma. In the stroma of benign lesions, the number of ASMA-positive stromal cells was various, but the stroma of all invasive breast cancers contained ASMA-positive stromal cells. The present results indicate that disappearance of CD34-positive stromal cells consistently occurs in the stroma of invasive carcinoma of the breast, irrespective of histological type and may be associated with the presence of ASMA-positive stromal cells.}, } @article {pmid15942148, year = {2005}, author = {Sezgin, N and Sezgin, AT and Gullu, H and Karabulut, A and Barutcu, I and Topal, E and Yalcintas, D and Temel, I}, title = {Decreased serum lipoprotein levels as a guide for clinical severity in patients with idiopathic dilated cardiomyopathy.}, journal = {The Tohoku journal of experimental medicine}, volume = {206}, number = {3}, pages = {219-224}, doi = {10.1620/tjem.206.219}, pmid = {15942148}, issn = {0040-8727}, mesh = {Adult ; Aged ; Apolipoprotein A-I/metabolism ; Apolipoproteins/metabolism ; Cardiomyopathy, Dilated/*blood/diagnosis ; Cholesterol/metabolism ; Cholesterol, HDL/metabolism ; Cholesterol, LDL/metabolism ; Cytokines/metabolism ; Echocardiography ; Female ; Glucose/metabolism ; Humans ; Interleukin-6/metabolism ; Lipoproteins/*blood/metabolism ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not fully clarified. It has been known that there is a direct relationship between the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and deteriorating functional classes of heart failure and mortality. The present study compared the levels of circulating TNF-alpha, IL-6, lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total cholesterol (TC) was significantly lower in stable IDC patients than controls (p < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but not statistically significant. The IDC patients had significantly higher concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and Apo AI levels were significantly different between stable and unstable IDC patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = -0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p < 0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum levels of cytokines in patients with IDC are associated with decreased lipoprotein concentrations, which may indicate impaired prognosis.}, } @article {pmid15923404, year = {2005}, author = {Peter, JC and Tugler, J and Eftekhari, P and Maurice, D and Hoebeke, J and Roegel, JC}, title = {Effects on heart rate of an anti-M2 acetylcholine receptor immune response in mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {19}, number = {8}, pages = {943-949}, doi = {10.1096/fj.04-3042com}, pmid = {15923404}, issn = {1530-6860}, mesh = {Allosteric Regulation ; Amino Acid Sequence ; Animals ; Antibodies/blood/*immunology/physiology ; Atropine/pharmacology ; CHO Cells ; Carbachol/pharmacology ; Cricetinae ; Cricetulus ; Cyclic AMP/analysis ; Electrocardiography ; Female ; Gallamine Triethiodide/pharmacology ; Heart Rate/drug effects/*physiology ; Humans ; Immunization ; Isoproterenol/pharmacology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Parasympathetic Nervous System/physiology ; Peptide Fragments/chemistry/immunology ; Receptor, Muscarinic M2/genetics/*immunology/physiology ; Transfection ; }, abstract = {Autoantibodies in vitro modulating the M2 acetylcholine receptor (M2ACh-R) were observed in patients with idiopathic dilated cardiomyopathy (IDC) or Chagas' cardiomyopathy (ChC). We investigated the in vivo consequences on heart rate of such antibodies in mice immunized with a peptide derived from the second extracellular loop of the M2ACh-R compared with mice immunized with an irrelevant peptide. Sera of mice immunized with the M2ACh-R-derived peptide recognized the M2ACh-R on immunoblots and enhanced agonist activity of carbachol toward the M2AChR transfected in CHO cells. In vivo, no difference could be shown in heart rate or heart rate variability between the two groups of mice. The decrease in heart rate induced by carbachol was more pronounced, however, in the M2ACh-R immunized mice. The increase in heart rate induced by atropine, gallamine, and isoproterenol was significantly attenuated in the M2ACh-R immunized mice. Analysis of heart rate variability further argued for an increased parasympathetic response to different drugs in the M2ACh-R immunized mice. Antibodies raised against the M2AChR can behave as positive M2AChR allosteric modulators in vivo. They might be protective in boosting the activity of the parasympathetic drive to the heart, especially in patients with a high sympathetic tone.}, } @article {pmid15917448, year = {2005}, author = {Oppenheim, JJ and Dong, HF and Plotz, P and Caspi, RR and Dykstra, M and Pierce, S and Martin, R and Carlos, C and Finn, O and Koul, O and Howard, OM}, title = {Autoantigens act as tissue-specific chemoattractants.}, journal = {Journal of leukocyte biology}, volume = {77}, number = {6}, pages = {854-861}, doi = {10.1189/jlb.1004623}, pmid = {15917448}, issn = {0741-5400}, support = {N01-CO-12400/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Neoplasm/*immunology ; Autoantigens/*immunology ; Autoimmune Diseases/*immunology ; Chemotactic Factors/*immunology ; Chemotaxis, Leukocyte/immunology ; Dendritic Cells/immunology ; Humans ; Leukocytes, Mononuclear/immunology ; Mice ; Neoplasms/*immunology ; }, abstract = {We have investigated the chemoattractant properties of self-antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi-protein-coupled receptors (GiPCR). Our initial observation that myositis-associated autoantigens, histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)- and CCR3-expressing leukocytes, while other nonautoantigenic aminoacyl-tRNA synthesases were not, suggested that only self-antigens capable of interacting with receptors on antigen-presenting cells were immunogenic. We next determined that self-antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10-100 ng/ml, but did not induce DC maturation until they reached 1000-fold higher concentrations. Interphotoreceptor retinoid-binding protein and retinal arrestin (S-antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)- and/or CXCR3-expressing iDC. However, although S-antigen does not induce EAU in wild-type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue-specific self-antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.}, } @article {pmid15915241, year = {2005}, author = {Granizo Martínez, JJ}, title = {[Resistance to penicillin and erythromycin of Streptococcus pneumoniae and Streptococcus pyogenes isolated from community-acquired respiratory infections in Spain between 1986-1999 and its relationship with the use of beta-lactams and macrolides].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {18}, number = {1}, pages = {83-85}, pmid = {15915241}, issn = {0214-3429}, mesh = {Community-Acquired Infections/microbiology ; Drug Resistance, Bacterial ; Drug Utilization/statistics & numerical data ; Erythromycin/*pharmacology ; Humans ; Macrolides/*therapeutic use ; *Penicillin Resistance ; Pneumonia, Bacterial/microbiology ; Pneumonia, Pneumococcal/*microbiology ; Spain ; Streptococcal Infections/*microbiology ; Streptococcus pneumoniae/*drug effects/isolation & purification ; Streptococcus pyogenes/*drug effects/isolation & purification ; beta-Lactams/*therapeutic use ; }, } @article {pmid15910716, year = {2005}, author = {Cellini, C and Huston, TL and Martins, D and Christos, P and Carson, J and Kemper, S and Simmons, RM}, title = {Multiple re-excisions versus mastectomy in patients with persistent residual disease following breast conservation surgery.}, journal = {American journal of surgery}, volume = {189}, number = {6}, pages = {662-666}, doi = {10.1016/j.amjsurg.2005.03.005}, pmid = {15910716}, issn = {0002-9610}, mesh = {Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; Mastectomy/*statistics & numerical data ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm, Residual ; Receptors, Progesterone/analysis ; Reoperation/statistics & numerical data ; Retrospective Studies ; }, abstract = {BACKGROUND: Persistently involved margins following breast conservation surgery (BCS) create a diagnostic dilemma regarding the recommendation of further BCS or mastectomy.

METHODS: A retrospective review of 276 breast cancer patients who underwent BCS and required additional surgical treatment between 1990-2002 was performed.

RESULTS: For treatment of persistently involved margins, 63% of subjects underwent re-excision the first time, 49% the second time, and 37% the third time. The incidence of residual carcinoma increased linearly with the number of initially involved margins (P = .03). Ductal carcinoma-in-situ (DCIS) or infiltrating lobular carcinoma (IFLC) primary histology was associated with a higher rate of residual cancer compared to invasive ductal carcinoma (IFDC) (62% vs. 69% vs. 54%, respectively, P = .56). A trend towards an increased risk of residual cancer in primary tumors > or =2 cm versus tumors under 2 cm was also evident (63%% vs. 50%, respectively, P = .38).

CONCLUSIONS: Approximately half of patients repeatedly selected BCS over mastectomy. It is important to realistically discuss the probability of definitive resection with patients who are undergoing breast conservation with re-excision.}, } @article {pmid15909708, year = {2005}, author = {Kidmas, AT and Ugwu, BT and Manasseh, AN and Iya, D and Opaluwa, AS}, title = {Male breast malignancy in Jos University Teaching Hospital.}, journal = {West African journal of medicine}, volume = {24}, number = {1}, pages = {36-40}, doi = {10.4314/wajm.v24i1.28160}, pmid = {15909708}, issn = {0189-160X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*diagnosis/epidemiology/physiopathology/therapy ; Child ; Hospitals, Teaching/statistics & numerical data ; Hospitals, University/*statistics & numerical data ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Staging ; Nigeria/epidemiology ; Patient Acceptance of Health Care ; Retrospective Studies ; Time Factors ; }, abstract = {BACKGROUND: Male breast malignancies are rare. Cancer of the male breast accounts for about 1% of all breast cancers. Poor level of awareness often results in late presentation and delayed diagnosis in our environment.

PATIENTS AND METHODS: A retrospective study of all cases of male breast cancer (MBC) managed in Jos University Teaching Hospital over a 17-year period (January 1987-December 2003.)

RESULTS: A total of 302 cases of breast malignancies were managed over the study period. Twenty-six (8.6%) of these were males giving a male:female ratio of 1:10.6. The ages of the 26 MBC cases ranged from 12 years to 85 years, with a mean of 57.9 years and median age of 67 years. The right breast was affected in 15 and the left in 11. Mean duration of symptoms before presentation was 6 months with a range of 3 months to 4 years. All the patients had history of breast lumps, 21 (80.8%) of which were painless. Skin ulceration and axillary node enlargement were present in 19(73.1%) and 24(92.3%) respectively. Five (19.2%) were stage II; 15(57.7%) stage III and 6(23.1%) stage IV. There were 23 (88.5%) carcinomas, 2 (7.7%) fibrosarcomas and a case of Hodgkin's lymphoma. Invasive ductal carcinoma was the most common histological type in 20 (76.9%) of all breast malignancy and 20 (87.0%) of all breast carcinomas. Modified radical mastectomy (mastectomy with axillary clearance with or without division of the pectoralis minor muscle) was done in 10(38.5%) patients. Two of these were fibrosarcomas. Simple mastectomy was done in 13 (50%) as toilet procedures for advanced disease. The only case of Hodgkin's lymphoma had chemotherapy. Bilateral orchidectomy (BO), Tamoxifen, chemotherapy and radiotherapy were offered in 7(26.9%), 13(50%), 17(65.4%) and 7(26.9%) patients respectively. Wound infection was the most common complication in 14(53.8%) patients. There was no case of hospital mortality.

CONCLUSION: MBC accounts for 8.6% of all breast cancers in our centre. It affects elderly males. Late presentation with advanced disease and ulceration is a common feature in our environment.}, } @article {pmid15900371, year = {2005}, author = {Khairy, GA and Guraya, SY and Ahmed, ME and Ahmed, MA}, title = {Bilateral breast cancer. Incidence, diagnosis and histological patterns.}, journal = {Saudi medical journal}, volume = {26}, number = {4}, pages = {612-615}, pmid = {15900371}, issn = {1658-3175}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/epidemiology/pathology ; Female ; Humans ; Incidence ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: Bilateral breast cancer is uncommon (1-2.6% of all patients with breast carcinoma). There are conflicting reports and inadequate data regarding the incidence and survival of such patients. This study examined the frequency, mode of detection, therapeutic modalities and histological features among the 2 breasts.

METHODS: Medical records of patients who were treated for breast cancer were reviewed at Khartoum Teaching Hospital, Sudan during a 5-year period of 1994 to 1999. Data of patients found to have bilateral breast cancer was analyzed focusing on the demographic information, family history, menstrual status, surgical therapy, chemoradiation, staging and histopathological characteristics.

RESULTS: Of 521 patients treated for breast cancer, 90 (17.2%) were reported to have advanced breast carcinoma (stage III, IV) and 7 (1.3%) revealed bilateral cancer: 5 (0.9%) synchronous and 2 (0.4%) metachronous breast cancer. The median age was 47.3 years (range, 24-81 years). Four (57.1%) patients had positive family history for breast cancer. First breast cancer was detected by mammogram in 2 cases while second cancer was diagnosed by the same study in 5 patients. Five (71.5%) underwent mastectomy and 2(28.5%) were treated by lumpectomy and axillary dissection. Six patients presented with stage III and one with stage IV breast cancer. Invasive ductal carcinoma was reported to be the most common type found in 10 (71.5%) breasts. Grade III breast carcinoma was revealed in 9 and Grade I cancer in 3 specimens.

CONCLUSION: Bilateral breast cancer is invariably advanced when diagnosed. Mammogram is a valuable tool in early detection. Whether synchronous or metachronous, both breasts often share the same histological type.}, } @article {pmid15899192, year = {2005}, author = {Sitges, M and Roig, E and Morales, M and Azqueta, M and Pérez Villa, F and Paré, C and Orús, J and Heras, M and Sanz, G}, title = {[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels].}, journal = {Revista espanola de cardiologia}, volume = {58}, number = {5}, pages = {477-483}, pmid = {15899192}, issn = {0300-8932}, mesh = {Arm/blood supply ; Cardiomyopathy, Dilated/*blood/complications/*physiopathology ; Endothelium, Vascular/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Tumor Necrosis Factor-alpha/*analysis ; Vasodilation ; Ventricular Dysfunction, Left/*blood/complications/*physiopathology ; }, abstract = {INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation.

PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time.

RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD.

CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.}, } @article {pmid15897740, year = {2005}, author = {Simpson, PT and Gale, T and Reis-Filho, JS and Jones, C and Parry, S and Sloane, JP and Hanby, A and Pinder, SE and Lee, AH and Humphreys, S and Ellis, IO and Lakhani, SR}, title = {Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis.}, journal = {The American journal of surgical pathology}, volume = {29}, number = {6}, pages = {734-746}, doi = {10.1097/01.pas.0000157295.93914.3b}, pmid = {15897740}, issn = {0147-5185}, support = {BREAST CANCER NOW RESEARCH CENTRE/BCN_/Breast Cancer Now/United Kingdom ; }, mesh = {*Biomarkers, Tumor ; Breast/*pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/*pathology ; Cell Transformation, Neoplastic ; Disease Progression ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Nucleic Acid Hybridization ; }, abstract = {Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER and PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma.}, } @article {pmid15896864, year = {2005}, author = {Satkunskiene, D and Schega, L and Kunze, K and Birzinyte, K and Daly, D}, title = {Coordination in arm movements during crawl stroke in elite swimmers with a loco-motor disability.}, journal = {Human movement science}, volume = {24}, number = {1}, pages = {54-65}, doi = {10.1016/j.humov.2005.04.001}, pmid = {15896864}, issn = {0167-9457}, mesh = {Adult ; Arm/*physiology ; Female ; Humans ; Locomotion/*physiology ; Male ; Movement Disorders/*physiopathology ; Psychomotor Performance/*physiology ; *Swimming ; }, abstract = {The purpose of this study was to investigate selected kinematics parameters of the arm stroke in crawl swimmers with disabilities and to examine the potential use of an index of arm coordination (IdC) to evaluate the stroking technique of swimmers with diverse functional abilities. The degree of overlap in the propulsive phases (superposition model) and lag time between the propulsive phases (catch-up model) was examined in 18 well-trained swimmers with loco-motor disabilities, 9 females and 9 males, from functional classes S3-S10 with S10 being most functional. Based on the results, correct coordination appears to be fundamental to swimming crawl stroke in both able-bodied swimmers as well as swimmers with a disability. Some swimmers with disabilities examined here exhibited extreme values at both ends of the index scale. This might be essential to maintaining balance while swimming when not all limb activity contributes to the forward movement.}, } @article {pmid15892087, year = {2005}, author = {Schimke, I and Müller, J and Dandel, M and Gremmels, HD and Bayer, W and Wallukat, B and Wallukat, G and Hetzer, R}, title = {Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study.}, journal = {Journal of clinical apheresis}, volume = {20}, number = {3}, pages = {137-142}, doi = {10.1002/jca.20050}, pmid = {15892087}, issn = {0733-2459}, mesh = {Adsorption ; Adult ; *Autoantibodies/blood/immunology ; Cardiomyopathy, Dilated/blood/immunology/*therapy ; Female ; *Hemodiafiltration/methods ; Humans ; Male ; Middle Aged ; *Oxidative Stress ; Pilot Projects ; *Receptors, Adrenergic, beta-1/blood/immunology ; *Recovery of Function ; Ventricular Function, Left ; }, abstract = {Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress--thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB)--were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance.}, } @article {pmid15887223, year = {2005}, author = {Santiago, RJ and Harris, EE and Qin, L and Hwang, WT and Solin, LJ}, title = {Similar long-term results of breast-conservation treatment for Stage I and II invasive lobular carcinoma compared with invasive ductal carcinoma of the breast: The University of Pennsylvania experience.}, journal = {Cancer}, volume = {103}, number = {12}, pages = {2447-2454}, doi = {10.1002/cncr.21071}, pmid = {15887223}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/pathology/*therapy ; Carcinoma, Ductal, Breast/pathology/*therapy ; Carcinoma, Lobular/pathology/*therapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: The objective of the current study was to determine the long-term results of breast-conservation treatment in women with early-stage, invasive lobular carcinoma of the breast.

METHODS: Between 1977 and 1995, 1093 women with Stage I and II invasive ductal carcinoma of the breast and 55 women with invasive lobular carcinoma of the breast underwent lumpectomy, axillary lymph node dissection, and radiation treatment. Overall, 49% of the women received adjuvant systemic therapy (chemotherapy and/or hormones).

RESULTS: The median age was 52 years for patients in the invasive ductal group and 54 years for patients in the invasive lobular group. The median follow-up was 8.7 years and 10.2 years for patients in the invasive ductal and invasive lobular groups, respectively. A comparison of patients who had invasive lobular carcinoma with patients who had invasive ductal carcinoma showed no difference in the 10-year actuarial rates of overall survival (85% vs. 79%, respectively; P = 0.73), cause-specific survival (93% vs. 84%, respectively; P = 0.85), or freedom from distant metastases (81% vs. 80%, respectively; P = 0.76). The 10-year rates of local failure were 18% for patients with invasive lobular carcinoma and 12% for patients with invasive ductal carcinoma (P = 0.24), and the 10-year rates of contralateral breast carcinoma development for the 2 groups were 12% and 8%, respectively (P = 0.40).

CONCLUSIONS: Breast-conservation treatment yielded similar long-term results for women with early-stage, invasive lobular carcinoma and women with the more prevalent invasive ductal carcinoma.}, } @article {pmid15879625, year = {2005}, author = {Moriya, T and Kimura, W and Semba, S and Sakurai, F and Hirai, I and Ma, J and Fuse, A and Maeda, K and Yamakawa, M}, title = {Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.}, journal = {International journal of gastrointestinal cancer}, volume = {35}, number = {2}, pages = {111-119}, pmid = {15879625}, issn = {1537-3649}, mesh = {Aged ; Bile Duct Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/*pathology ; Carcinoma, Papillary/*genetics/*pathology ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/*genetics/*pathology ; }, abstract = {BACKGROUND: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.

AIMS: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.

METHODOLOGY: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.

RESULTS: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).

CONCLUSIONS: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.}, } @article {pmid15871723, year = {2005}, author = {Yamasaki, T and Tsuda, H and Imazeki, N and Matsubara, O}, title = {Vascular endothelial growth factor mRNA levels quantified by reverse transcription-polymerase chain reaction in microdissected breast carcinoma tissues are correlated with histological type and grade of both invasive and intraductal components.}, journal = {Pathology international}, volume = {55}, number = {5}, pages = {255-263}, doi = {10.1111/j.1440-1827.2005.01822.x}, pmid = {15871723}, issn = {1320-5463}, mesh = {Adult ; Aged ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microdissection ; Middle Aged ; Neoplasm Invasiveness ; RNA, Messenger/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A/*genetics/metabolism ; }, abstract = {In breast cancer, vascular endothelial growth factor (VEGF) is a prognostic factor, but the relationship of VEGF mRNA levels with various parameters or tumor progression is unclear. VEGF mRNA levels were measured in 48 cases of invasive ductal carcinoma by using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean VEGF mRNA levels were compared among different histological types and grades in 41 and 29 samples of invasive and intraductal components, respectively. VEGF mRNA levels were always higher in cancerous cells than in non-cancerous cells, but mean VEGF mRNA levels were not significantly different between invasive component (3.24 +/- 3.18-fold the value of non-cancerous tissue) and intraductal component (4.14 +/- 4.43-fold). They were higher in papillotubular type than in other types, and higher in grade 2 carcinomas than in grade 3 carcinomas of invasive component, and higher in comedo type than in other types of intraductal component. Mean VEGF mRNA levels were higher in the VEGF-immunopositive group than in the VEGF-immunonegative group. There was no correlation between VEGF mRNA levels and tumor size, nodal status, or hormone receptor status. VEGF expression may play an important role in the development of both invasive and intraductal carcinoma components, especially those carcinoma components of less aggressive histological features.}, } @article {pmid15865092, year = {2005}, author = {Hashimoto, K and Nio, Y and Koike, M and Itakura, M and Yano, S and Higami, T and Maruyama, R}, title = {Expression of retinoblastoma and p53 pathway-related proteins in resectable invasive ductal carcinoma of the pancreas: potential cooperative effects on clinical outcome.}, journal = {Anticancer research}, volume = {25}, number = {2B}, pages = {1361-1368}, pmid = {15865092}, issn = {0250-7005}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/*metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Retinoblastoma Protein/*metabolism ; Survival Rate ; Time Factors ; Tumor Suppressor Protein p53/*metabolism ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: The retinoblastoma protein (RB) is an important cell cycle regulator. RB also plays an important role in the regulation of apoptosis, which is mediated by interaction of p53 signaling mediators. The present study was designed to assess the clinicopathological significance of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) expression in resectable invasive ductal carcinoma (IDC) of the pancreas.

MATERIALS AND METHODS: The present study included 79 pancreatic IDC patients, who received surgery between 1982 and 2002. The expression of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) were analyzed by immunohistochemistry.

RESULTS: RB was expressed in 45 (57%) of the 79 patients. RB expression correlated significantly with histological grade and grade of nodal involvement. The positive rate of p53, p21WAF1/CIP1 and Bax expression was 49%, 48% and 67%, respectively. RB expression alone did not have a significant effect on patient survival. However, coexpression analysis of RB and p53 pathway-related proteins indicated that, in the patients with RB (+) IDC, the p21WAF1/CIP1 (+) group had a significantly higher survival rate than the p21WAF1/CIP1 (-) group. On the other hand, in the patients with RB (-) IDC, the Bax (+) group had a significantly higher survival rate than the Bax (-) group. Multivariate analysis indicated that, in the RB (-) group, pTNM stage, adjuvant chemotherapy and Bax expression were significant variables.

CONCLUSION: The evaluation of RB expression combined with the mediators of the p53 pathway, p21WAF1/CIP1 and Bax, may provide more accurate information regarding clinical outcome, beyond that which is provided by RB expression alone.}, } @article {pmid15864214, year = {2005}, author = {Fernandez, C and Chetaille, B and Tasei, AM and Sastre, B and Sahel, J and Payan-Defais, MJ}, title = {From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis.}, journal = {Gastroenterologie clinique et biologique}, volume = {29}, number = {4}, pages = {465-468}, doi = {10.1016/s0399-8320(05)80818-8}, pmid = {15864214}, issn = {0399-8320}, mesh = {Carcinoma in Situ/diagnosis/*genetics/*physiopathology ; Cell Transformation, Neoplastic/*genetics ; Disease Progression ; Female ; Genes, ras/*genetics ; Humans ; Immunohistochemistry ; Middle Aged ; Pancreatic Neoplasms/diagnosis/*genetics/*physiopathology ; }, abstract = {Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a woman suffering from idiopathic chronic pancreatitis associated with PanINs lesions who developed six years later an invasive ductal carcinoma. Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene were performed at different stages of disease and revealed that the PanINs and the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras mutation was present at the carcinoma stage. The relationship between cancer and chronic pancreatitis and the main difficulties concerning the early diagnostic of pancreatic cancer are discussed.}, } @article {pmid15857596, year = {2005}, author = {Aziz, SA and Pervez, S and Khan, SM and Kayani, N and Nasir, MI}, title = {Prognostic value of proliferating cell nuclear antigen (PCNA) in infiltrating ductal carcinoma breast.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {15}, number = {4}, pages = {225-229}, pmid = {15857596}, issn = {1022-386X}, mesh = {Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Proliferating Cell Nuclear Antigen/*metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {OBJECTIVE: To assess the independent and interdependent prognostic value of proliferating cell nuclear antigen (PCNA) in carcinoma of breast in our female population and its association with pathologic variables and disease outcome.

DESIGN: A descriptive study.

PLACE AND DURATION OF STUDY: Section of Histopathology, Department of Pathology and Microbiology, The Aga Khan University, Karachi from January 1992 to December 1997.

PATIENTS AND METHODS: All cases diagnosed with invasive ductal carcinomas (IDC) of breast with lymph nodes sampling were included. The expression of PCNA was analyzed on tumor specimens of IDC breast. These patients also had axillary lymph node sampling. The expression of PCNA protein was analyzed immunohistochemically by PAP technique. Patients were followed for a median duration of 48 months.

RESULTS: The percentage of PCNA positive tumor cells was estimated semi-quantitatively. Positivity was seen in every case, mean PCNA positivity was 27% (range 10-80) with a median of 28%. The <25% positivity was seen in 149 (47%) cases, and >25% positivity seen in 166 (53%) cases. According to the pathological grading lowest mean PCNA was seen in grade-I i.e., 26% tumor cells showed nuclear reactivity to PCNA followed by grade-II 30% and grade-III 33%. PCNA categorical expression was significantly correlated with histological differentiation, (p<0.05) and tumor size (p<0.01). Distant metastases were seen in>25% positive cases (p<0.05). PCNA expression when correlated with overall survival, showed significant correlation between categorical PCNA (p<0.05). At a median follow-up of 48 months, 66% of <25 PCNA positive patients died with an overall survival of 3.16 years and disease-free survival of 2.5 years, among >25% PCNA positive patients 77% died with an overall survival of 2.7 years and a disease-free survival of 2.2 years.

CONCLUSION: In this study PCNA proved to be an independent prognostic indicator in predicting disease-free and overall survival in breast carcinoma patients.}, } @article {pmid15846392, year = {2005}, author = {Ogbagabriel, S and Fernando, M and Waldman, FM and Bose, S and Heaney, AP}, title = {Securin is overexpressed in breast cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {18}, number = {7}, pages = {985-990}, doi = {10.1038/modpathol.3800382}, pmid = {15846392}, issn = {0893-3952}, mesh = {Analysis of Variance ; Blotting, Northern ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Nucleus/chemistry ; Cytoplasm/chemistry ; Estrogen Receptor alpha/analysis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymph Nodes/pathology ; Mitotic Index ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*biosynthesis/genetics ; RNA, Messenger/genetics/metabolism ; Securin ; }, abstract = {Securin regulates sister chromatid separation during mitosis, induces bFGF-mediated angiogenesis, and securin overexpression causes in vitro transformation and in vivo tumor formation in nude mice. As estrogen administration to oophorectomized rats increased pituitary securin expression, we used immunohistochemistry to examine securin and estrogen receptor alpha (ER-alpha) expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin and ER-alpha expression were quantitated by image analysis and expressed as fold difference relative to securin expression in normal breast tissue. Low cytoplasmic securin expression was seen in the normal breast epithelium, whereas abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. Highest securin expression was seen in brain metastatic breast tumors (4.3-fold, P<0.01), cells derived from metastatic breast cancers (6.5-fold, P<0.001), and in invasive ductal carcinoma (mean+/-s.e.: 3.8-fold, P<0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors (1.6-fold) exhibited high immunohistochemical securin expression compared to low-grade breast tumors (P<0.05). Northern blot analysis in 12 of the breast tumors confirmed the immunohistochemical findings demonstrating increased securin mRNA expression compared to normal breast mucosa (2.5-fold, P=0.03), with highest securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P=0.03). In addition, some tumors that exhibited high securin expression also expressed high ER-alpha levels (P<0.0001). These results demonstrate that the estrogen-induced transforming gene, securin is abundantly expressed in breast carcinoma, and is associated with the presence of metastatic spread, and lymph node invasion. We propose immunohistochemical tumor securin expression as a potential invasive marker, and novel therapeutic target in breast cancer.}, } @article {pmid15845796, year = {2005}, author = {Sardanelli, F and Iozzelli, A and Fausto, A and Carriero, A and Kirchin, MA}, title = {Gadobenate dimeglumine-enhanced MR imaging breast vascular maps: association between invasive cancer and ipsilateral increased vascularity.}, journal = {Radiology}, volume = {235}, number = {3}, pages = {791-797}, doi = {10.1148/radiol.2353040733}, pmid = {15845796}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast/*blood supply ; Breast Neoplasms/*blood supply/*pathology ; *Contrast Media/administration & dosage ; Female ; *Gadolinium DTPA/administration & dosage ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Severity of Illness Index ; Single-Blind Method ; }, abstract = {PURPOSE: To retrospectively compare three different doses of gadobenate dimeglumine with a standard dose of gadopentetate dimeglumine for magnetic resonance (MR) imaging evaluation of breast vessels and to evaluate the accuracy of one-sided increased vascularity seen on gadobenate dimeglumine-enhanced MR images as an indicator of ipsilateral breast cancer.

MATERIALS AND METHODS: The original study had local ethics committee approval; informed consent was obtained from all enrolled patients. Ninety-five patients known to have or suspected of having breast cancer were randomly assigned to four groups to receive gadobenate dimeglumine at a dose of 0.05, 0.10, or 0.20 mmol per kilogram of body weight or gadopentetate dimeglumine at a dose of 0.10 mmol/kg. T1-weighted gradient-echo MR images were acquired before and 2 minutes after intravenous contrast material injection. Subtracted images were used to obtain maximum intensity projections (MIPs). Two readers blinded to the type and dose of contrast agent administered scored the MIPs obtained in the dose groups for vessel number, length, and conspicuity from 0, which indicated absent or low breast vascularity, to 3, which indicated high breast vascularity. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of one-sided increased vascularity in association with ipsilateral malignancy for 69 histopathologically confirmed lesions (reference standard) were determined after gadobenate dimeglumine-enhanced MR imaging.

RESULTS: The mean MIP scores assigned to the gadobenate dimeglumine groups were significantly higher than those assigned to the gadopentetate dimeglumine group (P < or = .044). Histopathologic analysis revealed malignant lesions in 52 of 69 patients examined with gadobenate dimeglumine MR imaging: invasive ductal carcinoma in 45, invasive lobular carcinoma in four, and invasive mixed ductal-lobular carcinoma in three patients. Seventeen patients had benign lesions. Two cases of bilateral invasive cancer with symmetric breast vascular maps were excluded. Thus, the overall sensitivity, specificity, accuracy, PPV, and NPV of one-sided increased vascularity as a finding associated with ipsilateral malignancy were 88% (44 of 50 patients), 82% (14 of 17 patients), 87% (58 of 67 patients), 94% (44 of 47 patients), and 70% (14 of 20 patients), respectively.

CONCLUSION: Gadobenate dimeglumine is effective for MR imaging evaluation of breast vessels at doses as low as 0.05 mmol/kg. One-sided increased vascularity is an MR imaging finding frequently associated with ipsilateral invasive breast cancer.}, } @article {pmid15844251, year = {2004}, author = {Tamiolakisl, D and Venizelos, I and Lambropoulou, M and Jivannakis, T and Seliniotakis, E and Tsikouras, P and Limberis, V and Tsalkidis, A and Papadopoulos, N}, title = {Gains and losses of HLA class II (DR) and CD4 in atypical hyperplasia, carcinoma in situ and infiltrating ductal carcinoma of the breast.}, journal = {Acta medica (Hradec Kralove)}, volume = {47}, number = {4}, pages = {257-262}, pmid = {15844251}, issn = {1211-4286}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/*immunology ; CD4 Antigens/analysis ; *CD4 Lymphocyte Count ; Carcinoma, Ductal, Breast/*immunology ; Carcinoma, Intraductal, Noninfiltrating/*immunology ; Female ; HLA-DR Antigens/*analysis ; Humans ; Hyperplasia/immunology ; Middle Aged ; }, abstract = {AIM: Breast cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with breast cancer, such as cellular immunotherapy. In this immunohistochemical study we analyzed the epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR) on atypical and malignant primary mammary epithelial cells, as well as the magnitude of the stromal T lymphocytes (T4 subset) at the tumor site.

EXPERIMENTAL DESIGN: The study was carried out retrospectively in tumor tissue from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia -ADH-, 12 cases of ductal carcinoma in situ -DCIS- and 39 cases of infiltrating ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not included in our investigation. Material used had been formalin fixed and paraffin embedded.

RESULTS: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4 of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of 31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDC-NOSs (67%).

CONCLUSIONS: The results showed decreased epithelial expression of HLA class II (DR) and increased stromal expression of CD4, as the lesion progressed to malignancy. Gradual loss of epithelial HLA class II expression might be a manifestation of cellular differentiation from the atypical form versus the malignant one, signaling simultaneously a selective effect on the response capacity of the immune system.}, } @article {pmid15842422, year = {2005}, author = {Alonso, JL and Martínez, P and Vallverdú, M and Cygankiewicz, I and Pitzalis, MV and Bayés Genís, A and Cinca, J and Rizzon, P and Caminal, P and Zareba, W and Bayés de Luna, A}, title = {Dynamics of ventricular repolarization in patients with dilated cardiomyopathy versus healthy subjects.}, journal = {Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc}, volume = {10}, number = {2}, pages = {121-128}, pmid = {15842422}, issn = {1082-720X}, mesh = {Adult ; Algorithms ; Cardiomyopathy, Dilated/*physiopathology ; *Electrocardiography, Ambulatory ; Female ; Heart Conduction System/*physiopathology ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Signal Processing, Computer-Assisted ; Ventricular Function, Left ; }, abstract = {BACKGROUND: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24-hour Holter ECG recordings.

METHODS: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24-hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds.

RESULTS: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients.

CONCLUSIONS: The automatic assessment of repolarization parameters in 24-hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T-wave morphology, the factors which might predispose them to the development of arrhythmic events.}, } @article {pmid15840906, year = {2005}, author = {Liesmaa, I and Kuoppala, A and Shiota, N and Kokkonen, JO and Kostner, K and Mäyränpää, M and Kovanen, PT and Lindstedt, KA}, title = {Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {288}, number = {5}, pages = {H2317-22}, doi = {10.1152/ajpheart.00815.2004}, pmid = {15840906}, issn = {0363-6135}, mesh = {Adult ; Cardiomyopathy, Dilated/physiopathology ; Coronary Disease/physiopathology ; Coronary Vessels/*physiology ; Endothelium, Vascular/*physiology ; Female ; Heart Failure/*physiopathology ; Humans ; Male ; Middle Aged ; RNA, Messenger/analysis ; Receptor, Bradykinin B1/*genetics ; Receptor, Bradykinin B2/genetics ; Tumor Necrosis Factor-alpha/genetics ; }, abstract = {In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure. Nothing is known about the expression of BK-1Rs in human heart failure. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13), due to idiopathic dilated cardiomyopathy (IDC; n = 7) or to coronary heart disease (CHD; n = 6), and from normal hearts (n = 6). The expression of BK-1Rs was analyzed by means of competitive RT-PCR, Western blot analysis, and immunohistochemistry. Expression of BK-1R mRNA was increased in both IDC (2.8-fold) and CHD (2.1-fold) hearts compared with normal hearts. The observed changes were verified at the protein level. Expression of BK-1Rs in failing hearts localized to the endothelium of intramyocardial coronary vessels and correlated with an increased expression of TNF-alpha in the vessel wall. Treatment of human coronary artery endothelial cells with TNF-alpha increases their BK-1R expression. These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure.}, } @article {pmid15840262, year = {2005}, author = {Mao, GY and Yang, J and Chen, HB and Guo, W and Nie, HX}, title = {[A study of phenotype and function of dendritic cells and secretory cytokine in allergic asthmatic patients].}, journal = {Zhonghua nei ke za zhi}, volume = {44}, number = {3}, pages = {206-209}, pmid = {15840262}, issn = {0578-1426}, mesh = {Adolescent ; Adult ; Asthma/*immunology ; Cytokines/*metabolism ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunophenotyping ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Male ; T-Lymphocytes/immunology ; }, abstract = {OBJECTIVE: To investigate the deficiency of the expression of the phenotypes (CD(1a), CD(83), CD(40), CD(86)) and cytokines (IL-12 and IL-10) by human peripheral blood monocyte (PBMC)-derived dendritic cell (DCs) from asthmatic subjects, and their influence on naive T cell polarization.

METHODS: Adherent cells were isolated from peripheral blood samples in asthmatic patients and in healthy volunteers, and were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 as immature DC (iDC). iDCs were stimulated with lipopolysaccharide as mature DC (mDCs). Nonadherent cells were obtained from umbilical cord blood by idem methods, and naïve T cells were sorted by adding anti-CD(4) and anti-CD(45RA) in nonadherent cells respectively and magnetic microbeads. Naïve T cells and mDCs from two groups were co-cultured in complete RPMI1640 media respectively, and naive T cells polarized as T helper cells 1 (Th1) and Th2. The expression of the CD(1a), CD(83), CD(40) and CD(86) on mature DCs were examined by fluorescent activated cell sorter. IL-12 and IL-10 released by mDCs and IL-4 and IFNgamma produced by Th cells were measured by ELISA.

RESULTS: (1) The expression of CD(86) on dendritic cells from atopic asthmatics was higher than that from healthy control subjects (40.75 +/- 3.99 vs 29.88 +/- 1.25, P < 0.01). (2) The levels of IL-12, IL-12p40 and IL-10 produced by DCs from asthmatic subjects were all significantly lower than those from healthy control group (217.79 +/- 118.65 vs 905.66 +/- 495.32, P < 0.01; 2072.22 +/- 1496.37 vs 5569.43 +/- 2922.75, P < 0.01; 336.89 +/- 261.52 vs 1425.00 +/- 1148.87, P < 0.05, respectively). (3) IL-4 production by Th2 cells which were primed by DCs from asthmatics was significantly increased as compared to that from control group (368.56 +/- 190.72 vs 584.91 +/- 290.13, P < 0.01); On the contrary, IFNgamma in the patient group was reduced as compared to that in the control group (425.33 +/- 164.94 vs 49.86 +/- 18.14, P < 0.05). (4) In the patient group, the level of IL-12 was positively correlated to that of IFNgamma (P < 0.05), negatively correlated to that of IL-4 (P < 0.05); IL-10 was negatively correlated to IL-4 (P < 0.05). (5) There was a positive correlation between IL-12 and IL-10 in the two groups (P < 0.01).

CONCLUSION: Because of DC deficiency, naïve T cells preferentially polarize to Th2 which synthesize more Th2-type cytokine (i.e. IL-4) and T cell tolerance cannot be induced, which may be one of the important pathogenic mechanisms for allergic asthma.}, } @article {pmid15837543, year = {2005}, author = {Parrella, P and Scintu, M and Prencipe, M and Poeta, ML and Gallo, AP and Rabitti, C and Rinaldi, M and Tommasi, S and Paradiso, A and Schittulli, F and Valori, VM and Toma, S and Altomare, V and Fazio, VM}, title = {HIC1 promoter methylation and 17p13.3 allelic loss in invasive ductal carcinoma of the breast.}, journal = {Cancer letters}, volume = {222}, number = {1}, pages = {75-81}, doi = {10.1016/j.canlet.2004.08.026}, pmid = {15837543}, issn = {0304-3835}, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 17/genetics ; *DNA Methylation ; DNA Mutational Analysis ; DNA, Neoplasm/analysis ; DNA-Binding Proteins ; Female ; Humans ; Kruppel-Like Transcription Factors ; Microsatellite Repeats ; *Promoter Regions, Genetic ; Transcription Factors/*genetics ; }, abstract = {The HIC1 gene is a transcriptional regulator commonly methylated in a variety of human cancer. Thirty-three invasive ductal carcinomas of the breast and 21 matched normal breast tissues were analysed for HIC1 promoter methylation, and allelic loss of a 700 kb region spanning the gene locus. At least one genetic or epigenetic abnormality was found in 27 of the carcinomas tested (82%). Promoter methylation was demonstrated in 21 carcinomas (64%), and nine normal tissues (43%), whereas 18 malignant tumors (54%) showed allelic loss. Concomitant loss of heterozigosity and promoter hypermethylation in the region spanning HIC1 was detected in eight carcinomas (24%) suggesting that in this subset of tumors both copies of the gene are functionally lost. These observations support a role for the HIC1 gene in the pathogenesis of breast ductal carcinomas.}, } @article {pmid15832647, year = {2005}, author = {Gogo-Abite, M and Nwosu, SO}, title = {Histopathological characteristics of female breast carcinomas seen at the University of Port Harcourt Teaching Hospital, Port Harcourt Nigeria.}, journal = {Nigerian journal of medicine : journal of the National Association of Resident Doctors of Nigeria}, volume = {14}, number = {1}, pages = {72-76}, doi = {10.4314/njm.v14i1.37139}, pmid = {15832647}, issn = {1115-2613}, mesh = {Biopsy, Needle ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma/*epidemiology/*pathology ; Developing Countries ; Female ; Hospitals, Teaching ; Humans ; Immunohistochemistry ; Incidence ; Neoplasm Invasiveness/*pathology ; Neoplasm Staging ; Nigeria/epidemiology ; Prognosis ; Registries ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: Breast carcinoma is an unpredictable disease in the sense that some patients may present with relatively early disease and die of widespread metastases within six months to one year, while others present with fairy advanced disease and yet survive longer. The aim of this study was to characterize breast carcinomas into prognostic groups using histological features.

METHODOLOGY: A total of 269 breast carcinomas in females received during a five-year period (January 1991 to December 1995 inclusive) were analyzed. Archive records (request forms and microscopic slides) of all breast malignancies diagnosed in the department of Anatomical Pathology of University of Port Harcourt Teaching Hospital were retrieved and evaluated with respect to histological type, histological grades, and mononuclear cell infiltration within the primary tumour. The modified Bloom-Richardson system of microscopic grading of breast carcinoma was used.

RESULTS: The majority of carcinomas showed scanty or absent tubule formation (43.1%) and 59% of cases showed numerous mitotic figures. Forty-nine percent of carcinomas show poorly differentiated or anaplastic nuclei. The final tumour grade (FG) which is the summation of tubular pattern, nuclear pleomorphism and mitotic grades of each of the tumours reveals that 53% fall in FG3, 26% in FG2while only 21% fall in FG1. The majority of the breast carcinomas in this study, 58%, show scanty or absent mononuclear infiltration.

CONCLUSION: The majority of breast carcinomas in this study are poorly differentiated invasive ductal carcinoma, "not otherwise specified" which exhibit high proliferation ratio and are associated with poor host cellular immune reaction. These attributes translate to poor prognosis.}, } @article {pmid15832194, year = {2005}, author = {Furukawa, T and Fujisaki, R and Yoshida, Y and Kanai, N and Sunamura, M and Abe, T and Takeda, K and Matsuno, S and Horii, A}, title = {Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {18}, number = {8}, pages = {1034-1042}, doi = {10.1038/modpathol.3800383}, pmid = {15832194}, issn = {0893-3952}, mesh = {Adenocarcinoma, Mucinous/genetics/metabolism/*pathology ; Adenocarcinoma, Papillary/genetics/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA Mutational Analysis/methods ; DNA-Binding Proteins/metabolism ; Disease Progression ; Dual Specificity Phosphatase 6 ; Humans ; Immunohistochemistry ; Mutation ; Pancreatic Ducts/metabolism/pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Precancerous Conditions/metabolism/*pathology ; Protein Tyrosine Phosphatases/*metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Signal Transduction ; Smad4 Protein ; Trans-Activators/metabolism ; Tumor Suppressor Protein p53/metabolism ; ras Proteins ; }, abstract = {DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer. The aim of this study was to elucidate the roles of DUSP6 in the pancreatic carcinogenesis through the pancreatic intraepithelial neoplasia and/or intraductal papillary-mucinous neoplasms, both of which are considered to be precursor lesions of invasive carcinoma of the pancreas, by comparing with involvements of other major tumor suppressive pathways. Expressions of DUSP6, CDKN2A, TP53, and SMAD4 were investigated by immunohistochemistry in a total of 206 lesions of dysplastic ductal precursors and carcinomas retrieved from 52 pancreata with invasive ductal carcinomas and 51 of those with intraductal papillary-mucinous neoplasms. The intensity of staining was evaluated in lesions at different atypical grades and statistically compared among them. Mutations of KRAS2 were analyzed by methods of the allele-specific oligonucleotide hybridization and nucleotide sequencing. In pancreata with invasive ductal carcinomas, expressions of DUSP6 were abrogated exclusively in the invasive carcinoma cells in contrast to its fairly preserved expressions in pancreatic intraepithelial neoplasia. In pancreata with intraductal papillary-mucinous neoplasms, abrogated expressions of DUSP6 were observed in a relatively small fraction of intraductal adenoma/borderlines and intraductal carcinomas. Most of the intraductal adenoma/borderline lesions with abrogation of DUSP6 harbored mutations of KRAS2. None of the molecules was associated with each other in any grade of lesions. Morphological variations of papillae of the intraductal papillary-mucinous neoplasms were evaluated and analyzed for their associations with abrogations of the molecules, which resulted in finding of no significant associations. Our results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma while it is potentially associated with initiation of intraductal papillary-mucinous neoplasms with mutated KRAS2, which is independent of other major tumor suppressive pathways in both types of neoplasms.}, } @article {pmid15830137, year = {2005}, author = {Man, YG and Fu, SW and Schwartz, A and Pinzone, JJ and Simmens, SJ and Berg, PE}, title = {Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion.}, journal = {Breast cancer research and treatment}, volume = {90}, number = {3}, pages = {241-247}, doi = {10.1007/s10549-004-4492-9}, pmid = {15830137}, issn = {0167-6806}, support = {CA 91149/CA/NCI NIH HHS/United States ; K08 CA 101875/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/*pathology ; Case-Control Studies ; Disease Progression ; Female ; *Gene Expression Profiling ; Homeodomain Proteins/*biosynthesis ; Humans ; Neoplasm Invasiveness/*genetics ; RNA, Messenger/biosynthesis ; Transcription Factors/*biosynthesis ; }, abstract = {BACKGROUND: Our previous studies revealed that the mRNA encoded by BP1, a member of the homeobox gene superfamily of transcription factors, was expressed in leukemia and infiltrating breast ductal carcinoma (IDC). This study investigated the immunohistochemical profile of BP1, to determine whether the expression of BP1 protein correlated with breast tumor progression and invasion and whether BP1 was co-localized with erbB2.

DESIGN: Paraffin sections from normal reduction mammoplasties (n = 34) and a variety of in situ and invasive breast cancers (n = 270) were either singly immunostained for BP1, or doubly immunostained for BP1 plus either erbB2 or Ki-67.

RESULTS: The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and carcinogenesis. BP1 expression was barely detectable in normal reduction mammoplasties compared to distinct staining in 21, 46, and 81% of hyperplastic, in situ, and infiltrating lesions, respectively. In cases with co-existing normal, hyperplastic, in situ, and invasive lesions, the tumor cells of the invasive lesions consistently showed the highest frequency and the highest intensity of BP1 immunostaining, followed by in situ tumor cells. Double immunostaining revealed that BP1 co-localized with a subset of erbB2 positive cells in all 15 in situ and IDC tumors examined, and that BP1 positive cells had a substantially higher proliferation rate than morphologically similar cells without BP1 expression.

CONCLUSION: These findings suggest that BP1 is an important upstream factor in an oncogenic pathway, and that expression of BP1 may reliably reflect or directly contribute to tumor progression and/or invasion.}, } @article {pmid15825206, year = {2005}, author = {Terenji, A and Willmann, S and Osterholz, J and Hering, P and Schwarzmaier, HJ}, title = {Measurement of the coagulation dynamics of bovine liver using the modified microscopic Beer-Lambert law.}, journal = {Lasers in surgery and medicine}, volume = {36}, number = {5}, pages = {365-370}, doi = {10.1002/lsm.20178}, pmid = {15825206}, issn = {0196-8092}, mesh = {*Algorithms ; Animals ; Blood Coagulation/*radiation effects ; Body Temperature/radiation effects ; Cattle ; In Vitro Techniques ; *Laser Coagulation ; Liver/*radiation effects ; Refractometry ; Spectrum Analysis/*methods ; }, abstract = {BACKGROUND AND OBJECTIVES: During heating, the optical properties of biological tissues change with the coagulation state. In this study, we propose a technique, which uses these changes to monitor the coagulation process during laser-induced interstitial thermotherapy (LITT).

Untreated and coagulated (water bath, temperatures between 35 degrees C and 90 degrees C for 20 minutes.) samples of bovine liver tissue were examined using a Nd:YAG (lambda = 1064 nm) frequency-domain reflectance spectrometer. We determined the time integrated intensities (I(DC)) and the phase shifts (Phi) of the photon density waves after migration through the tissue. From these measured quantities, the time of flight (TOF) of the photons and the absorption coefficients of the samples were derived using the modified microscopic Beer-Lambert law.

RESULTS: The absorption coefficients of the liver samples decreased significantly with the temperature in the range between 50 degrees C and 70 degrees C. At the same time, the TOF of the investigated photos was found increased indicating an increased scattering. The coagulation dynamics could be well described using the Arrhenius formalism with the activation energy of 106 kJ/mol and the frequency factor of 1.59 x 10(13)/second.

CONCLUSIONS: Frequency-domain reflectance spectroscopy in combination with the modified microscopic Beer-Lambert (MBL) is suitable to measure heat induced changes in the absorption and scattering properties of bovine liver in vitro. The technique may be used to monitor the coagulation dynamics during local thermo-coagulation in vivo.}, } @article {pmid15824180, year = {2005}, author = {Li, CI and Daling, JR and Malone, KE}, title = {Age-specific incidence rates of in situ breast carcinomas by histologic type, 1980 to 2001.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {14}, number = {4}, pages = {1008-1011}, doi = {10.1158/1055-9965.EPI-04-0849}, pmid = {15824180}, issn = {1055-9965}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*epidemiology/pathology ; Carcinoma, Lobular/*epidemiology/pathology ; Female ; Humans ; Incidence ; Middle Aged ; Regression Analysis ; SEER Program ; United States/epidemiology ; }, abstract = {Incidence rates of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have increased rapidly over the past several decades largely due to the increased use of mammography. However, recent data from 1987 to 1999 indicate that invasive ductal carcinoma incidence rates have remained essentially constant, whereas rates of invasive lobular carcinoma have increased 65%, with greater increases observed among postmenopausal women. Data on recent trends in DCIS and LCIS incidence rates, particularly age-specific trends, are lacking. We evaluated trends in the incidence rates of DCIS overall, noncomedo DCIS, comedo DCIS, and LCIS using data from nine Surveillance, Epidemiology, and End Results cancer registries. DCIS incidence rates increased 7.2-fold [95% confidence interval (95% CI), 6.8-7.7] from 1980 to 2001, 1.8-fold (95% CI, 1.7-1.9) over the past 10 years (1992-2001), and 1.1-fold (95% CI, 1.0-1.2) over the past 5 years (1997-2001). The magnitudes of these increases were highest among women ages > or = 50 years. Furthermore, over the past 10- and 5-year periods, rates of noncomedo DCIS have generally increased across all age groups, whereas rates of comedo DCIS held constant or decreased. LCIS incidence rates increased 2.6-fold (95% CI, 2.3-2.9) from 1980 to 2001, 1.3-fold (95% CI, 1.2-1.5) over the past 10 years, and 1.1-fold (95% CI, 1.0-1.3) over the past 5 years. Similar to invasive lobular carcinoma, but unlike invasive ductal carcinoma, incidence rates of both DCIS and LCIS continue to increase in the United States primarily among older women. These trends present important public health and clinical challenges.}, } @article {pmid15816611, year = {2005}, author = {Sheen-Chen, SM and Eng, HL and Chen, WJ and Cheng, YF and Ko, SF}, title = {Adenoid cystic carcinoma of the breast: truly uncommon or easily overlooked?.}, journal = {Anticancer research}, volume = {25}, number = {1B}, pages = {455-458}, pmid = {15816611}, issn = {0250-7005}, mesh = {Aged ; Breast/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma, Adenoid Cystic/*diagnosis/diagnostic imaging ; Female ; Humans ; Image Processing, Computer-Assisted ; Mammography/*methods ; Pain ; Ultrasonography, Mammary/methods ; }, abstract = {BACKGROUND: Adenoid cystic carcinoma of the breast is an uncommon histologic form of breast cancer, comprising in most series less than 1% of all mammary cancers. Due to the rarity, little information about its presentation on image studies has been noted in the literature. Here we report two additional cases with emphasis on the intriguing image presentations.

CASE ONE: A 67-year-old woman came to our clinic with the chief complaint of mastodynia. No obvious palpable mass of breast was found on physical examination. Mammography showed a small well-defined nodule in the medial part of the left breast without mammographic evidence of malignancy. Ultrasonography showed a 1.5 cm nodule with well-defined margin and heterogenous echogenicity in the medial part of the left breast. Unusually, a painful sensation was experienced on compression by the probe. The final pathological report was adenoid cystic carcinoma.

CASE TWO: A 48-year-old woman also came to our clinic with the chief complaint of mastodynia. No obvious palpable mass of breast was found on physical examination. Mammography showed dense mammary tissue with no mammographic evidence of malignancy. Ultrasonography showed two contiguous well-defined nodules with heterogenous echogenicity in the upper, middle part of the left breast. Unusually, a painful sensation was also noted on compression by the probe. Histopathological examination showed typical features of an adenoid cystic carcinoma.

CONCLUSION: Adenoid cystic carcinoma of the breast fails to show the typical appearance of invasive ductal carcinoma on both mammogram and ultrasonography, probably due to its relatively well-defined nature with less surrounding architectural disruption and fibrosis. Hence a "negative" finding or a benign-looking breast lesion on mammography cannot completely exclude the existence of this disease. The presence of a painful breast lesion without obvious inflammatory evidence while compressed is a meaningful clue, which should lead to the suspicion of adenoid cystic carcinoma of the breast.}, } @article {pmid15816121, year = {2005}, author = {Kinkor, Z and Skálová, A}, title = {[Acinic cell-like differentiation in invasive ductal carcinoma and in ductal hyperplasia of the breast--report of two cases].}, journal = {Ceskoslovenska patologie}, volume = {41}, number = {1}, pages = {29-33}, pmid = {15816121}, issn = {1210-7875}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Acinar Cell/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Hyperplasia ; }, abstract = {Described are two epithelial lesions of the breast displaying extremely rare, widespread acinic cell-like differentiation (metaplasia). Two women, 70 and 40-year-old, one with invasive ductal papillocarcinoma, the other one with conventional intraductal hyperplasia without atypia, both demonstrated massive diffuse, PAS positive, granular eosinophilic transformation of the cell cytoplasm. This unusual cell appearance closely simulated acinar cells in normal serous salivary gland/acinic cell carcinoma or Paneth cells. Both extensive expression of lysozyme and finding of numerous zymogen granules ultrastructurally confirmed the acinic cell-like fenotype. Discussed is differential diagnosis of the breast neoplasm containing overt eosinophilic and granular cytoplasm. Reviewing literature and comparing our unique finding of unusual salivary-type differentiation in conventional ductal hyperplasia of the breast, biologic implications are considered.}, } @article {pmid15812750, year = {2005}, author = {Cinquegrana, G and D'Aniello, L and Landi, M and Spinelli, L and Grande, G and De Prisco, F and Petretta, M}, title = {Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {11}, number = {3}, pages = {213-219}, doi = {10.1016/j.cardfail.2004.07.006}, pmid = {15812750}, issn = {1071-9164}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/blood/*drug therapy/physiopathology ; Carvedilol ; Echocardiography ; Female ; Heart Failure/blood/*drug therapy/physiopathology ; Humans ; Interleukin-1/blood ; Interleukin-6/blood ; Male ; Metoprolol/*therapeutic use ; Middle Aged ; Myocardial Ischemia/blood/*drug therapy/physiopathology ; Propanolamines/*therapeutic use ; Stroke Volume/drug effects/physiology ; Tumor Necrosis Factor-alpha/analysis ; Ventricular Remodeling/drug effects/physiology ; }, abstract = {BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC).

METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group (P < .01).

CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC.}, } @article {pmid15812230, year = {2005}, author = {Feder-Mengus, C and Schultz-Thater, E and Oertli, D and Marti, WR and Heberer, M and Spagnoli, GC and Zajac, P}, title = {Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.}, journal = {Human gene therapy}, volume = {16}, number = {3}, pages = {348-360}, doi = {10.1089/hum.2005.16.348}, pmid = {15812230}, issn = {1043-0342}, mesh = {Animals ; Antibodies, Monoclonal/metabolism ; Antigen-Presenting Cells/*immunology/metabolism ; Antigens, Neoplasm ; CD4-Positive T-Lymphocytes/*immunology ; CD40 Antigens/*immunology/metabolism ; CD40 Ligand/immunology/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Cell Line ; Chlorocebus aethiops ; Cytokines/genetics/metabolism ; Cytotoxicity Tests, Immunologic ; DNA Primers ; Flow Cytometry ; Genetic Vectors ; Immunity, Cellular/*immunology ; Immunotherapy/*methods ; Interleukin-12/metabolism ; Interleukin-12 Subunit p40 ; Ligands ; Lymphocyte Activation/immunology ; MART-1 Antigen ; Neoplasm Proteins/metabolism ; Neoplasms/immunology/*therapy ; Protein Subunits/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vaccinia virus/genetics/*immunology ; }, abstract = {Recombinant poxviruses expressing immunomodulatory molecules together with specific antigens represent powerful vaccines for cancer immunotherapy. Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens. To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV). Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities. Therefore, we evaluated the effects of CD154rVV infection on APC activation and its consequences on T cell stimulation. CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC. Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies. Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection. As expected, VV infection triggered cytokines gene expression in cultures including APC and T cells from VV immune donors. However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV. Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA). In the presence of CD154rVV activated APCs, significantly higher numbers of specific cytotoxic CD8+ T cells were detected, as compared with cultures performed in the presence of WT VV or in the absence of virus. Taken together, these data indicate that functional CD154 expression from rVV infected cells promotes APC activation, thereby enhancing antigen-specific T cell generation. Such a recombinant vector might help bypass the requirement for activated helper cells during CTL priming, thus qualifying as a potentially relevant vector in the generation of CD8+ T cell responses in cancer immunotherapy.}, } @article {pmid15810296, year = {1998}, author = {Li, H and Kong, F}, title = {[The constant-in time DC component in the time-resolved FTIR spectroscopy].}, journal = {Guang pu xue yu guang pu fen xi = Guang pu}, volume = {18}, number = {2}, pages = {152-157}, pmid = {15810296}, issn = {1000-0593}, abstract = {The direct current component in the interferogram of conventional FTIR spectroscopy is expressed by integral(infinity)0 B(sigma)dsigma. However, in time-resolved FTIR spectroscopy, the direct current component Idc(tau) also depends upon tau, the time which IR signal appears. Idc(tau) is then represented by integral(infinity)0 B(sigma, tau)dsigma, called as constant-in-time DC component by us. Idc(tau) is proportional to the signal intensity B(sigma). Idc(tau) can not be filtered by any band pass filter. After Fourier transforming, the Idc(tau) converts to a strong peak at 0cm(-1) in the IR spectrum. We call it as constant-in-time zero frequency signal Btau(0). Either Idc or Btau(0) can be used to monitor a variety of experimental conditions, such as the variation of gas pressure, laser intensity, the carbon deposition on the optics, etc. They can also be applied to measure the instrumental response time and the band pass frequency.}, } @article {pmid15808750, year = {2005}, author = {Burkett, EL and Hershberger, RE}, title = {Clinical and genetic issues in familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {45}, number = {7}, pages = {969-981}, doi = {10.1016/j.jacc.2004.11.066}, pmid = {15808750}, issn = {0735-1097}, support = {NIH R01 HL 58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/diagnostic imaging/*genetics ; Echocardiography ; Electrocardiography ; Family ; Genetic Counseling ; Genetic Testing ; Humans ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular dilatation and systolic dysfunction after known causes have been excluded. Idiopathic dilated cardiomyopathy occurring in families, or familial dilated cardiomyopathy (FDC), may occur in 20% to 50% of IDC cases. Sixteen genes have been shown to cause autosomal dominant FDC, but collectively may account for only a fraction of genetic causation; it is anticipated that additional genes causative of FDC will be discovered. Familial dilated cardiomyopathy demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making clinical and genetic diagnosis complex. Echocardiographic and electrocardiographic screening of first-degree relatives of individuals with IDC and FDC is indicated, as detection and treatment are possible before the onset of advanced symptomatic disease. Genetic counseling for IDC and FDC is also indicated to assist with family evaluations for genetic disease and with the uncertainty and anxiety surrounding the significance of clinical and genetic evaluation. Genetic testing is not yet commonly available, but its emergence will provide new opportunities for presymptomatic diagnosis.}, } @article {pmid15802534, year = {2005}, author = {Semino, C and Angelini, G and Poggi, A and Rubartelli, A}, title = {NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.}, journal = {Blood}, volume = {106}, number = {2}, pages = {609-616}, doi = {10.1182/blood-2004-10-3906}, pmid = {15802534}, issn = {0006-4971}, mesh = {Calcium Signaling ; Cell Communication/immunology ; Cell Differentiation ; Cell Polarity ; Cytokines/biosynthesis ; Cytotoxicity, Immunologic ; Dendritic Cells/cytology/*immunology/metabolism ; HMGB1 Protein/*biosynthesis ; Humans ; In Vitro Techniques ; Interleukin-18/*biosynthesis/pharmacology ; Killer Cells, Natural/drug effects/*immunology/metabolism ; Recombinant Proteins/pharmacology ; Tubulin/metabolism ; }, abstract = {Interaction of natural killer (NK) cells with autologous immature dendritic cells (DCs) results in reciprocal activation; however, the underlying mechanisms are so far elusive. We show here that NK cells trigger immature DCs to polarize and secrete interleukin 18 (IL-18), a cytokine lacking a secretory leader sequence. This occurs through a Ca2+-dependent and tubulin-mediated recruitment of IL-18-containing secretory lysosomes toward the adhering NK cell. Lysosome exocytosis and IL-18 secretion are restricted at the synaptic cleft, thus allowing activation of the interacting NK cells without spreading of the cytokine. In turn, DC-activated NK cells secrete the proinflammatory cytokine high mobility group B1 (HMGB1), which induces DC maturation and protects DCs from lysis. Also HMGB1 is a leaderless cytokine that undergoes regulated secretion. Differently from IL-18, soluble HMGB1 is consistently detected in NK/DC supernatants. These data point to secretion of leaderless cytokines as a key event for the reciprocal activation of NK cells and DCs. DCs initiate NK cell activation by targeted delivery of IL-18, thus instructing NK cells in the absence of adaptive-type cytokines; in turn, activated NK cells release HMGB1, which promotes inflammation and induces DC maturation, thus favoring the onset of the adaptive immune response.}, } @article {pmid15799760, year = {2005}, author = {Zheng, W and Zheng, J and Ma, L and Meng, F and Huang, L and Ma, D}, title = {Comparison of HER-2/neu, ER and PCNA expression in premenopausal and postmenopausal patients with breast carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {113}, number = {3}, pages = {175-181}, doi = {10.1111/j.1600-0463.2005.apm1130304.x}, pmid = {15799760}, issn = {0903-4641}, mesh = {Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/*diagnosis/immunology/pathology ; Carcinoma, Ductal, Breast/*diagnosis/immunology/pathology ; Cell Membrane/chemistry/immunology ; Cell Nucleus/chemistry/immunology ; Cell Proliferation ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; *Postmenopause ; *Premenopause ; Proliferating Cell Nuclear Antigen/analysis/*metabolism ; Receptor, ErbB-2/analysis/*metabolism ; Receptors, Estrogen/analysis/*metabolism ; }, abstract = {We attempted to compare the pattern of HER-2/neu, ER and PCNA in premenopausal and postmenopausal patients with breast carcinoma to identify potential biological differences. Five hundred and forty-eight samples from 318 premenopausal and 230 postmenopausal women with invasive ductal carcinoma of the breast were evaluated for HER-2/neu, ER and PCNA expression by immunohistochemistry. HER-2/neu expression showed 27.4% positivity in premenopausal and 24.8% in postmenopausal women; there was no significant difference between the two groups (p>0.05). In contrast, HER-2/neu expression was found to be significantly associated with ER negativity in the two groups (p<0.05 in premenopausal, p<0.001 in postmenopausal patients). However, it was significantly associated with PCNA expression only in the postmenopausal group (p<0.001). 54.4% showed premenopausal tumor cell ER positivity, whereas 64.3% of the postmenopausal group showed positivity. ER expression showed a significant correlation with patient menopausal status (p<0.05). The prevalence of PCNA positivity in the tumor cell components is slightly higher in postmenopausal compared to premenopausal women (p>0.20). The current study is consistent with reports from other groups regarding the correlation of HER-2/neu with adverse pathologic features and with expression of other markers in carcinoma. We also observed there was no trend toward increased HER-2/neu expression in either premenopausal or postmenopausal patients, i.e. there was similar HER-2/neu expression in the two groups. This suggests that HER-2/neu status could be used to determine assignment to specific intensive adjuvant therapy and evaluation of biological behavior in both pre- and postmenopausal patients with breast carcinoma.}, } @article {pmid15795813, year = {2005}, author = {Seifert, L and Boulesteix, L and Carter, M and Chollet, D}, title = {The spatial-temporal and coordinative structures in elite male 100-m front crawl swimmers.}, journal = {International journal of sports medicine}, volume = {26}, number = {4}, pages = {286-293}, doi = {10.1055/s-2004-821010}, pmid = {15795813}, issn = {0172-4622}, mesh = {Adult ; Arm ; Competitive Behavior/*physiology ; Humans ; Leg ; Male ; Psychomotor Performance/*physiology ; Spatial Behavior/*physiology ; Swimming/*physiology/psychology ; Task Performance and Analysis ; Time Factors ; }, abstract = {This study analysed the spatial-temporal and coordinative structures in 12 elite male 100-m front crawl swimmers. Swim performance was analysed over each length of a 25-m pool divided into five zones of 5 m. Velocity (V), stroke rate (SR), and stroke length (SL) were calculated for each zone and each length. Four stroke phases were identified by video analysis and the Index of Coordination (IdC) was established. Three modes of coordination were identified: catch-up (IdC < 0), opposition (IdC = 0), and superposition (IdC > 0). The swimmers tended to reduce the decrease in V and SR over the course of the 100 m by maintaining a stable SL. In fact, these spatial-temporal values were stable during the time spent stroking and were higher or lower during the start, the turns (in and out), and the finish. Thus the spatial-temporal changes did not occur within the lengths, but between them. Conversely, the evolution in the IdC showed that the swimmers had to install the stroke at the beginning and only reached a stable coordination in the second part of the race. Moreover, the IdC increased throughout the different zones of each 25-m length, indicating changes in motor organisation, particularly increases in the push or pull phases. The IdC values corresponded to a superposition of the arms, linked to a six-beat leg kick. Achievement of an effective superposition coordination occurred by boosting the stroke just after the turn-out until the end of the length. Regarding the spatial-temporal and coordinative structures of a 100-m front crawl, great swimming skill was reflected by both high and stable data.}, } @article {pmid15795104, year = {2005}, author = {Takeda, Y and Yoshikawa, K}, title = {Contrast-enhanced dynamic MR imaging parameters and histological types of invasive ductal carcinoma of breast.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {59}, number = {3}, pages = {115-121}, doi = {10.1016/j.biopha.2004.08.022}, pmid = {15795104}, issn = {0753-3322}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/classification/diagnosis/*pathology ; Carcinoma, Ductal, Breast/classification/diagnosis/*pathology ; Female ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; }, abstract = {The diagnosis of breast cancer has progressed owing to the improvement of both MRI equipments and MR techniques. CE-MRI is expected to be more useful for diagnosis of the existence and characteristics of breast cancer than mammography and ultrasound. Forty-three breast cancer patients, who underwent breast MRI examination before surgery and had histologically confirmed invasive ductal carcinomas, were included in this study. In 19, seven and 17 of them, carcinomas were histologically classified as papillotubular, solid-tubular, and scirrhous type, respectively. In dynamic MRI studies, the MR parameters were calculated from the signal intensity determined before and at five time-points after a bolus of 0.1 mmol Gd-DTPA/kg in the chosen region of interest (ROI). The differential analysis of MR parameters with reference to histopathology was performed by one-way analysis of variance (ANOVA) in dynamic studies. Four of 15 parameters analyzed, ENH1-2, ENH1, MSLP, and SAT3, were significantly different between papillotubular and scirrhous carcinoma. The dynamic curve of papillotubular carcinoma reached a maximum in the very early phase and then decreased slowly (linear pattern), while that of scirrhous carcinoma peaked in the slightly later phase and then decreased (parabolic pattern). In the differential analysis by Kruskal-Wallis test, although no significant differences were found in any morphological parameters among three histological types, spicula formation and rim enhancement tended to appear comparatively frequently in scirrhous and solid-tubular carcinoma. CE-MRI might reveal the differences of growth characteristics among different histological types of breast carcinomas and provide a diagnostic method useful for estimation of the prognosis of breast cancer.}, } @article {pmid15790698, year = {2005}, author = {Busund, LT and Richardsen, E and Busund, R and Ukkonen, T and Bjørnsen, T and Busch, C and Stalsberg, H}, title = {Significant expression of IGFBP2 in breast cancer compared with benign lesions.}, journal = {Journal of clinical pathology}, volume = {58}, number = {4}, pages = {361-366}, pmid = {15790698}, issn = {0021-9746}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/pathology ; Carcinoma in Situ/chemistry/pathology ; Epithelial Cells/metabolism/pathology ; Female ; Humans ; Hyperplasia/metabolism ; Image Processing, Computer-Assisted/methods ; Immunohistochemistry/methods ; Insulin-Like Growth Factor Binding Protein 2/*analysis ; Mammary Glands, Human/chemistry/pathology ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Proteins/*analysis ; Precancerous Conditions/chemistry/pathology ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {BACKGROUND/AIM: Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play a role in the normal development of breast tissue, and possibly in breast cancer aetiology. IGFBP2, one of six members of the IGFBP superfamily, acts as regulator of the IGFs and has pleiotropic effects in normal and neoplastic tissues. Because IGFs have mitogenic effects on mammary epithelia, this study investigated IGFBP2 expression in mammary tissues of different benign and malignant entities.

METHODS: Immunohistochemistry was used to study correlations between the presence and intensity of IGFBP2 staining and tumour type and grade, in addition to steroid hormone receptor status, in 120 breast specimens. Expression was measured by quantitative colour video image analysis and semiquantitative evaluation, and the measurements correlated well (r = 0.92; p<0.05).

RESULTS: Both methods found no significant expression of IGFBP2 in normal glandular cells and hyperplasia (group I). Atypical hyperplasia showed a slightly increased cytoplasmic expression of IGFBP2, and carcinoma in situ showed a distinctive, membrane associated and cytoplasmic expression (group II). Infiltrating carcinomas strongly expressed cytoplasmic IGFBP2 (group III). There were significant differences between group I and II, and between group II and III. There were no significant differences between invasive lobular and invasive ductal carcinoma, or between grades I, II, and III within these entities. There was no significant correlation between IGFBP2 immunostaining and oestrogen or progesterone receptor positivity within the malignant group.

CONCLUSIONS: IGFBP2 mitogenic signals of autocrine/paracrine regulatory mechanisms may be responsible for the growth of breast carcinomas and IGFBP2 may be an independent indicator of malignancy.}, } @article {pmid15785303, year = {2005}, author = {Parissis, JT and Adamopoulos, S and Karatzas, D and Paraskevaidis, J and Livanis, E and Kremastinos, D}, title = {Growth hormone-induced reduction of soluble apoptosis mediators is associated with reverse cardiac remodelling and improvement of exercise capacity in patients with idiopathic dilated cardiomyopathy.}, journal = {European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology}, volume = {12}, number = {2}, pages = {164-168}, doi = {10.1097/01.hjr.0000159320.70090.3d}, pmid = {15785303}, issn = {1741-8267}, mesh = {Apoptosis/drug effects ; Cardiomyopathy, Dilated/*diagnosis/*drug therapy ; Cross-Over Studies ; Cytokines/*blood ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Enzyme-Linked Immunosorbent Assay ; Exercise Tolerance/*drug effects ; Fas Ligand Protein ; Female ; Follow-Up Studies ; Growth Hormone/*therapeutic use ; Heart Function Tests ; Humans ; Injections, Subcutaneous ; Male ; Membrane Glycoproteins/*blood ; Probability ; Reference Values ; Risk Assessment ; Treatment Outcome ; Tumor Necrosis Factors/blood ; }, abstract = {OBJECTIVE: Recent experimental and clinical data indicate that abnormal inflammatory and apoptotic processes contribute to the progression of chronic heart failure (CHF). We sought to study the effects of growth hormone (GH) on circulating soluble apoptosis mediators, and to investigate whether these GH-induced anti-apoptotic effects are associated with the reduction of left ventricular (LV) volumes and attenuation of exercise intolerance in idiopathic dilated cardiomyopathy (IDC) patients.

METHODS: Plasma tumour necrosis factor-alpha (TNF-alpha), its soluble receptors sTNFRI and sTNFRII, and plasma apoptosis mediators soluble Fas (sFas) and sFas Ligand (sFAsL) were measured (enzyme-linked immunosorbent assay) in 12 IDC patients (NYHA III; LVEF: 24+/-2%) before and after a 3-month subcutaneous administration of GH 4 IU every other day (randomized, crossover design). Peak oxygen uptake (VO2max), as well as LV volume indices, wall thickness, and end-systolic wall stress (ESWS) were also determined at the same period.

RESULTS: Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 versus 5.5+/-0.9 pg/ml, P<0.02), sTNFRI (4.0+/-0.4 versus 3.3+/-0.3 ng/ml, P<0.05), sTNFRII (2.8+/-0.3 versus 2.4+/-0.2 ng/ml, P<0.05), sFas (4.7+/-0.7 versus 3.3+/-0.5 ng/ml, P<0.05) and sFasL (33.5+/-9.7 versus 20.2+/-6.2 pg/ml, P<0.01). A significant reduction in ESWS (841+/-62 versus 634+/-48 g/cm, P<0.01), LV end-systolic volume index (LVESVI, 128+/-12 versus 102+/-12 ml/m, P<0.001) and LV end-diastolic volume index (LVEDVI, 228+/-16 versus 200+/-18 ml/m, P<0.01) as well as a significant increase in VO2max (15.3+/-0.7 versus 17.1+/-0.9 ml/kg per min, P<0.01) were also observed in the patient population after GH administration. Significant correlations were found between the GH-induced decrease of sTNFRII and sFasL and respective reduction of LVESVI.

CONCLUSION: Growth hormone administration reduces circulating TNF system and soluble apoptosis mediators in patients with IDC. These GH-induced anti-apoptotic effects may be associated with the improvement in exercise capacity as well as with the reverse of LV remodelling in patients with CHF and IDC.}, } @article {pmid15782094, year = {2005}, author = {Nakata, B and Nishino, H and Ogawa, Y and Yokomatsu, H and Kawasaki, F and Kosaka, K and Wada, T and Suto, R and Montani, A and Hirakawa, K}, title = {Prognostic predictive value of endoscopic ultrasound findings for invasive ductal carcinomas of pancreatic head.}, journal = {Pancreas}, volume = {30}, number = {3}, pages = {200-205}, doi = {10.1097/00006676-200504000-00002}, pmid = {15782094}, issn = {1536-4828}, mesh = {Adenocarcinoma/diagnostic imaging ; Adenocarcinoma, Papillary/diagnostic imaging ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*diagnostic imaging ; *Endosonography/standards ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*diagnostic imaging ; Predictive Value of Tests ; Prognosis ; Reproducibility of Results ; }, abstract = {OBJECTIVES: Accurate preoperative prediction of the prognosis of patients with invasive ductal carcinoma of pancreatic head (pancreatic head cancer) is important for selecting treatment methods. We retrospectively examined the prognostic predictive values of endoscopic ultrasound (EUS) findings for patients with this disease.

METHODS: The subjects were 66 patients with pancreatic head cancer who had undergone EUS. We examined each EUS finding as a possible prognostic predictor, including heterogeneity of internal echo, irregularity of peripheral echo, clarity of boundary echo, dilatation of the main pancreatic duct (MPD), dilatation of the common bile duct, lymph node swelling, vessel invasion, and the presence of ascites, by univariate and multivariate analysis for survival.

RESULTS: Irregular peripheral echo, portal vein invasion, superior mesenteric artery/celiac artery invasion, and the presence of ascites were significant predictors of a poorer prognosis by univariate analysis for survival. In resectable cases, EUS findings of MPD dilatation and portal invasion were significant prognostic predictors by univariate analysis, and MPD dilatation was an independent prognostic predictor by multivariate analysis.

CONCLUSION: EUS may be useful for predicting the prognosis of patients with pancreatic head cancer, based on the accuracy it provides in evaluating locoregional spreading.}, } @article {pmid15779300, year = {2005}, author = {Skálová, A and Ryska, A and Kajo, K and Kinkor, Z}, title = {[Cystic hypersecretory carcinoma: rare and potentially aggressive variant of intraductal carcinoma of the breast. Report of five cases].}, journal = {Ceska gynekologie}, volume = {70}, number = {1}, pages = {73-78}, pmid = {15779300}, issn = {1210-7832}, mesh = {Aged ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; }, abstract = {OBJECTIVE: To describe a poorly recognized histological and immunohistochemical features of cystic hypersecretory carcinoma of breast, including the overexpression of HER-2/neu protein and androgen receptors.

SUBJECT: Review of clinical and pathological features of 5 cases of cystic hypersecretory carcinoma.

SETTING: Private Bioptic Lab, Plzen and Department of Pathology, Charles University, Plzen.

SUBJECT AND METHODS: Five cases of rare variant of intraductal carcinoma of the breast, so-called cystic hypersecretory carcinoma, are reported. The patients were females aged between 53 and 78 years (average 66.8 years). The size of the lesions ranged between 7 and 8 cm in largest dimension.

RESULTS: In two cases, the development of high grade invasive ductal carcinoma was observed; in one additional case there was recurrence of high grade in situ carcinoma after three years. Strong overexpression of HER-2/neu protein was observed in three cases including those two with invasive component. Protein p53 was variably positive in all cases. Steroid receptor immunohistochemical study yielded variable results with only one case being positive for both estrogen and progesterone receptors. Interestingly, in most case (4/5) staining for androgen receptors was observed.

CONCLUSION: The importance of correct diagnosis of this potentially aggressive lesion is emphasized. The differential diagnosis of breast lesions with predominantly cystic growth pattern is discussed in detail.}, } @article {pmid15778950, year = {2005}, author = {Watzinger, N and Lund, GK and Saeed, M and Reddy, GP and Araoz, PA and Yang, M and Schwartz, AB and Bedigian, M and Higgins, CB}, title = {Myocardial blood flow in patients with dilated cardiomyopathy: quantitative assessment with velocity-encoded cine magnetic resonance imaging of the coronary sinus.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {21}, number = {4}, pages = {347-353}, doi = {10.1002/jmri.20274}, pmid = {15778950}, issn = {1053-1807}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*physiopathology ; Coronary Circulation/*physiology ; Dipyridamole ; Female ; Heart Failure/physiopathology ; Humans ; Magnetic Resonance Imaging, Cine/*methods ; Male ; Microcirculation/physiopathology ; Middle Aged ; *Vasodilator Agents ; }, abstract = {PURPOSE: To quantify global myocardial perfusion using magnetic resonance imaging (MRI) in patients with heart failure due to idiopathic dilated cardiomyopathy (IDC) and to compare myocardial perfusion and microvascular reactivity with healthy subjects.

MATERIALS AND METHODS: A total of 19 subjects (healthy volunteers (N = 12) and IDC patients (N = 7)) were studied using cine MRI to measure left ventricular (LV) mass and a velocity-encoded cine MRI technique to measure coronary sinus flow at rest and after dipyridamole-induced hyperemia. Absolute values of total myocardial blood flow (MBF) were calculated from coronary sinus flow and LV mass.

RESULTS: At baseline, MBF was not significantly different in patients with IDC (0.48 +/- 0.07 mL/minute/g) and healthy subjects (0.55 +/- 0.19 mL/minute/g, P= 0.41). After dipyridamole administration, MBF in IDC patients increased to a level significantly less than that in normal volunteers (1.05 +/- 0.35 mL/minute/g vs. 1.99 +/- 1.05 mL/minute/g, P < 0.05). Consequently, MBF reserve was impaired in patients with IDC (2.19 +/- 0.77) compared to that in healthy subjects (3.51 +/- 1.29, P < 0.05). A moderate correlation was found between MBF reserve and LV ejection fraction (r = 0.48, P < 0.05).

CONCLUSION: MBF reserve is reduced in patients with IDC, indicating that coronary microcirculatory flow is impaired. This integrated MRI approach allows quantitative measurement of global MBF in humans and may have the potential to study the effects of pharmacological interventions on myocardial perfusion.}, } @article {pmid15778382, year = {2005}, author = {Buettner, M and Meinken, C and Bastian, M and Bhat, R and Stössel, E and Faller, G and Cianciolo, G and Ficker, J and Wagner, M and Röllinghoff, M and Stenger, S}, title = {Inverse correlation of maturity and antibacterial activity in human dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {174}, number = {7}, pages = {4203-4209}, doi = {10.4049/jimmunol.174.7.4203}, pmid = {15778382}, issn = {0022-1767}, mesh = {Bacteria/growth & development/*immunology ; Bronchoalveolar Lavage ; *Cell Differentiation ; Cells, Cultured ; Dendritic Cells/*cytology/*immunology ; Humans ; *Immunity, Innate ; Immunophenotyping ; Macrophages, Alveolar/immunology ; Mycobacterium tuberculosis/growth & development/immunology ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Dendritic cells (DCs) are a key part of host defense against microbial pathogens, being part of the innate immune system, but also instructing the adaptive T cell response. This study was designed to evaluate whether human DCs directly contribute to innate immunity by killing intracellular bacteria, using tuberculosis as a model. DCs were detected in bronchoalveolar lavage samples indicating that DCs are available for immediate interaction with Mycobacterium tuberculosis (M. Tb) after inhalation of the pathogen. The phenotype of DC in bronchoalveolar lavage closely resembles monocyte-derived immature DC (iDC) according to the expression of CD1a, CD83, and CCR7. The antimicrobial activity of iDC against intracellular M. Tb inversely correlated with TNF-alpha-release and was enhanced by treatment with anti-TNF-alpha Abs. Differentiation of iDC into mature DC by addition of TNF-alpha or activation via Toll-like receptors further reduced killing of M. Tb. The antibacterial activity against intracellular M. Tb of all DCs was significantly lower than alveolar macrophages. Therefore, the maintenance of a pool of DCs at the site of disease activity in tuberculosis, and the maturation of these DC by TNF-alpha provides a mechanism by which M. Tb escapes the innate immune system.}, } @article {pmid15770294, year = {2005}, author = {Agarwal, AK and Venugopalan, P and Meharali, A and de Bono, D}, title = {Survival analysis of patients with idiopathic dilated cardiomyopathy in Oman.}, journal = {Saudi medical journal}, volume = {26}, number = {2}, pages = {220-224}, pmid = {15770294}, issn = {0379-5284}, mesh = {Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/epidemiology ; Cardiomyopathy, Dilated/epidemiology/*mortality/physiopathology ; Comorbidity ; Female ; Humans ; Male ; Oman/epidemiology ; Prospective Studies ; Stroke Volume ; Survival Analysis ; }, abstract = {OBJECTIVE: To study the 10-year survival of adults with idiopathic dilated cardiomyopathy (IDC) in Oman.

METHODS: Ninety-seven patients aged >13 years with IDC attending the Cardiology Unit, Sultan Qaboos University Hospital, Muscat, Oman from 1992-1995 were prospectively studied, in order to identify the outcome and factors contributing to death.

RESULTS: Among 97 patients, 2 died from acute heart failure at presentation. The remaining 95 patients were followed up for periods ranging from 1-10 years (median 7 years). Twenty-four out of 95 patients exhibited clinical deterioration with reduced left ventricular ejection fraction (LVEF), by 5-11%, and 17 of them expired due to resistant heart failure. The remaining 71 patients remained stable and did not show deterioration in LVEF; however, 7 of them died suddenly at home possibly from ventricular arrhythmia. The survival rates were 94% at one year (95% confidence interval [CI] 88% to 99%), 86% at 3 years (95% CI 79% to 93%), and 64% at 10 years (95% CI 51% to 78%). Mean survival was 6.5 years (95% CI 6 to 7 years). Multivariate regression analysis revealed that factors related to death were LVEF <30% (p<0.001) and presence of severe mitral regurgitation (p=0.01).

CONCLUSION: Outcome of dilated cardiomyopathy has improved due to greater understanding of this condition leading to better therapeutic approach. Resistant heart failure and cardiac arrhythmias remain the main causes of mortality. Poor outcome was related to low LVEF and presence of severe mitral regurgitation.}, } @article {pmid15759182, year = {2005}, author = {Jersenius, U and Arvidsson, D and Lindholm, J and Anttila, S and Elvin, A}, title = {Radiofrequency ablation in the liver close to the bile ducts: can intraductal cooling offer protection?.}, journal = {Surgical endoscopy}, volume = {19}, number = {4}, pages = {546-550}, pmid = {15759182}, issn = {1432-2218}, mesh = {Animals ; Bile Ducts/diagnostic imaging/*injuries ; Body Temperature ; Catheter Ablation/*adverse effects ; Feasibility Studies ; *Hypothermia, Induced ; Intraoperative Complications/*prevention & control ; Liver/diagnostic imaging/*surgery ; Monitoring, Intraoperative ; Sus scrofa ; Treatment Failure ; Ultrasonography, Interventional ; }, abstract = {BACKGROUND: One complication of radiofrequency ablation (RFA) of the liver is biliary duct damage. Intraductal cooling (IDC) has been proposed as a means of protection.

METHODS: In the first experiment, designed to evaluate the influence of IDC on the RFA procedure per se and on lesion formation, lesions were created in vivo in pig liver with and without IDC. The RFA needle was placed with a 1.5-cm safety margin from the bile ducts. In the second experiment, designed to evaluate the potential protective effects of IDC, lesions were created close to a bile duct with and without IDC.

RESULTS: With the safety margin, the RFA parameters and lesion size were not negatively affected by IDC. Microscopic examination revealed that IDC had a protective effect in most of the lesions created close to a bile duct.

CONCLUSIONS: The IDC procedure was feasible and had no negative effect on the RFA procedure or the lesions. However, the protective effect of IDC was not statistically significant (p = 0.12).}, } @article {pmid15756255, year = {2005}, author = {Hasebe, T and Sasaki, S and Imoto, S and Wada, N and Ishii, G and Ochiai, A}, title = {Primary tumour-vessel tumour-nodal tumour classification for patients with invasive ductal carcinoma of the breast.}, journal = {British journal of cancer}, volume = {92}, number = {5}, pages = {847-856}, pmid = {15756255}, issn = {0007-0920}, mesh = {Breast Neoplasms/*blood supply/*classification/mortality/pathology/surgery ; Carcinoma, Ductal, Breast/*blood supply/*classification/mortality/pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Staging ; Neovascularization, Pathologic/*pathology ; Recurrence ; Retrospective Studies ; Survival Analysis ; Time Factors ; }, abstract = {There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour-vessel tumour-nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.}, } @article {pmid15746244, year = {2005}, author = {Klein, E and Koch, S and Borm, B and Neumann, J and Herzog, V and Koch, N and Bieber, T}, title = {CD83 localization in a recycling compartment of immature human monocyte-derived dendritic cells.}, journal = {International immunology}, volume = {17}, number = {4}, pages = {477-487}, doi = {10.1093/intimm/dxh228}, pmid = {15746244}, issn = {0953-8178}, mesh = {Antigens, CD ; Dendritic Cells/*immunology ; Endosomes/immunology ; Golgi Apparatus/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunoglobulins/*immunology ; Membrane Glycoproteins/*immunology ; Time Factors ; }, abstract = {Dendritic cells (DC) change their phenotype and functional properties during maturation. CD83 cell surface expression is induced on mature DC (mDC). In this study, we investigated intracellular CD83 localization and transport in human monocyte-derived DC. The enhanced level of CD83 cell surface expression in mDC resulted predominantly from increased protein synthesis, and in addition from regulated intracellular transport of CD83 protein. An internal pool of CD83 protein is present in immature DC (iDC). Although CD83 protein in iDC and in mDC was localized in the Golgi compartment and in recycling endosomes, only in mature cells did CD83 co-localize with MHC class II molecules in endocytic vesicles. CD83 cell surface expression on iDC was induced by inhibition of endocytosis. This result could be explained by CD83 cycling between endosomes and the cell surface in iDC. The mDC also rapidly internalized membrane-bound CD83 protein. Furthermore, a thiol protease inhibitor and specific cathepsin inhibitors impaired CD83 up-regulation in DC, indicating a role of endosomal proteases in the maturation-induced exposure of CD83 on the plasma membrane.}, } @article {pmid15743520, year = {2005}, author = {Frangou, EM and Lawson, J and Kanthan, R}, title = {Angiogenesis in male breast cancer.}, journal = {World journal of surgical oncology}, volume = {3}, number = {1}, pages = {16}, pmid = {15743520}, issn = {1477-7819}, abstract = {BACKGROUND: Male breast cancer is a rare but aggressive and devastating disease. This disease presents at a later stage and in a more advanced fashion than its female counterpart. The immunophenotype also appears to be distinct when compared to female breast cancer. Angiogenesis plays a permissive role in the development of a solid tumor and provides an avenue for nutrient exchange and waste removal. Recent scrutiny of angiogenesis in female breast cancer has shown it to be of significant prognostic value. It was hypothesized that this holds true in invasive ductal carcinoma of the male breast. In the context of male breast cancer, we investigated the relationship of survival and other clinico-pathological variables to the microvascular density of the tumor tissue. METHODS: Seventy-five cases of primary male breast cancer were identified using the records of the Saskatchewan Cancer Agency over a period of 26 years. Forty-seven cases of invasive ductal carcinoma of the male breast had formalin-fixed paraffin-embedded tissue blocks that were suitable for this study. All cases were reviewed. Immunohistochemical staining was performed for the angiogenic markers (cluster designations 31 (CD31), 34 (CD34) and 105 (CD105), von Willebrand factor (VWF), and vascular endothelial growth factor (VEGF)). Microvascular density (MVD) was determined using average, centre, and highest microvessel counts (AMC, CMC, and HMC, respectively). Statistical analyses compared differences in the distribution of survival times and times to relapse between levels of MVD, tumor size, node status and age at diagnosis. In addition, MVD values were compared within each marker, between each marker, and were also compared to clinico-pathological data. RESULTS: Advanced age and tumor size were related to shorter survival times. There were no statistically significant differences in distributions of survival times and times to relapse between levels of MVD variables. There was no significant difference in MVD between levels of the different clinico-pathological variables. MVD was strongly and significantly correlated between AMC, CMC and HMC for CD31, CD34, and CD105 (p < 0.01) and remained moderate to weak for VWF and VEGF. CONCLUSION: Microvascular density does not appear to be an independent prognostic factor in male breast cancer. However, the likelihood of death for men with breast cancer is increased in the presence of increased age at diagnosis and advanced tumor size. This is perhaps linked to inherent tumor vasculature, which is strongly related throughout a tumor section.}, } @article {pmid15741305, year = {2005}, author = {Amano, G and Yajima, M and Moroboshi, Y and Kuriya, Y and Ohuchi, N}, title = {MRI accurately depicts underlying DCIS in a patient with Paget's disease of the breast without palpable mass and mammography findings.}, journal = {Japanese journal of clinical oncology}, volume = {35}, number = {3}, pages = {149-153}, doi = {10.1093/jjco/hyi044}, pmid = {15741305}, issn = {0368-2811}, mesh = {Biopsy ; Breast Neoplasms/*diagnosis/pathology/surgery ; Breast Self-Examination ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology/surgery ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Mastectomy, Modified Radical ; Middle Aged ; Nipples/*pathology ; Paget's Disease, Mammary/*diagnosis/pathology/surgery ; }, abstract = {Breast-conserving therapy must be carefully indicated among patients with Paget's disease of the breast, because the disease is often associated with an underlying in situ or invasive carcinoma, even when there are no palpable mass or mammography findings. We report a 52-year-old woman who complained of skin color change of her right nipple for 11 months. No mass was palpable in her breasts, and mammography did not show any density or calcification. Nipple biopsy revealed Paget's disease of the breast with ductal carcinoma in situ (DCIS) in the breast epithelium just beneath the nipple. Magnetic resonance imaging (MRI) of the breast demonstrated diffuse segmental enhancement in two different quadrants. According to the pattern of enhancement, the lesions depicted by MRI were diagnosed as an extensively spreading type of DCIS. Based on informed consent, the patient received a total mastectomy. The histopathological examination demonstrated non-invasive ductal carcinoma with comedo-necrosis. The histological mapping with subserial sectioning demonstrated an extent of the lesions that corresponded accurately to the lesions defined by MRI. We conclude that MRI may play an important role in selecting candidates for breast-conserving therapy out of those patients with mammary Paget's disease with no clinical evidence of an underlying breast carcinoma.}, } @article {pmid15736718, year = {2004}, author = {Ozbilgin, MK and Polat, S and Mete, UO and Tap, O and Kaya, M}, title = {Antigen-presenting cells in the hypertrophic pharyngeal tonsils: a histochemical, immunuhistochemical and ultrastructural study.}, journal = {Journal of investigational allergology & clinical immunology}, volume = {14}, number = {4}, pages = {320-328}, pmid = {15736718}, issn = {1018-9068}, mesh = {Antigen-Presenting Cells/*physiology ; Child ; Child, Preschool ; Dendritic Cells, Follicular/physiology ; HLA-DR Antigens/analysis ; Humans ; Hypertrophy ; Immunohistochemistry ; Microscopy, Electron ; Palatine Tonsil/immunology/*pathology/ultrastructure ; Pharynx/immunology/*pathology/ultrastructure ; }, abstract = {The antigen presenting cells (APCs) with special interest to dendritic cells (DC), were investigated in 28 hypertrophic and 10 control pharyngeal tonsils of children by histochemistry, immunohistochemistry and electron microscopy. In this study, we are trying to clarify the function and classification of APC in pharyngeal tonsils using morphologic criteria, Human Leukocyte Antigen Monoclonal Antibody (HLA-DR MoAb), which is specific for APCs, and acid phosphatase (APh) reacting with both phagosomes and lysosomes. The surface epithelium of the patient group examined by light microscopy, heavy infiltration of lymphocytes, degenerated columnar cells and a few HLA-DR MoAb (+) columnar cells was observed. Additionally, a significant number of APCs which were Langerhans cells (LCs), interdigitating dendritic cell (IDC), follicular dendritic cell (FDC) and macrophages were stained with both HLA-DR MoAb and APh in the epithelial, interfollicular-subepithelial and follicular areas. Ultrastructural examinations revealed that lymphocytes, macrophages, LC and M cells were found among the surface columnar epithelial cells of the patient group. The interactions between M cells and LC suggested that M cells probably passed antigens from surface to LC. In the interfollicular-subepithelial areas of the hypertrophic pharyngeal tonsil, IDCs were in close contact with lymphocytes, macrophages and plasma cells. Seven types of FDCs (FDC-1 - FDC-7) were recognised according to their ultrastructural appearances. Differentiated FDCs (FDC-4) were also in close contact with each active subtype of FDCs in follicular areas besides lymphocytes. These findings supported the idea that although the pharyngeal tonsils contained several types of active APCs, only DC were in close contact with immunocompetent cells and the other APC's. Therefore, these morphologic appearances of DC could be a sign of function to initiate the immune response of the pharyngeal tonsil.}, } @article {pmid15735855, year = {2005}, author = {Kuroda, N and Sugimoto, T and Takahashi, T and Moriki, T and Toi, M and Miyazaki, E and Hiroi, M and Enzan, H}, title = {Invasive micropapillary carcinoma of the breast: an immunohistochemical study of neoplastic and stromal cells.}, journal = {International journal of surgical pathology}, volume = {13}, number = {1}, pages = {51-55}, doi = {10.1177/106689690501300107}, pmid = {15735855}, issn = {1066-8969}, mesh = {Actins/analysis ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology ; Cadherins/*analysis ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Papillary/chemistry/*pathology ; Cytoskeletal Proteins/*analysis ; Female ; Fibroblasts/chemistry/pathology ; Humans ; Middle Aged ; Mucin-1/*analysis ; Stromal Cells/chemistry/*pathology ; Trans-Activators/*analysis ; beta Catenin ; }, abstract = {A 59-year-old woman complained of a palpable mass in the right breast, and a needle biopsy disclosed small clusters of neoplastic cells in the fibrous stroma. The small clusters did not contain fibrovascular cores but exhibited micropapillary configuration. Epithelial membrane antigen (EMA) immunohistochemistry confirmed the reverse polarity of the neoplastic cells. Additionally, the plasma membrane of many neoplastic cells stained with E-cadherin and beta-catenin. Myofibroblasts, which were positive for alpha smooth muscle actin (ASMA) and negative for cytokeratin 14, were abundant in the neoplastic stroma, but no CD34-positive stromal cells were observed in the neoplastic stroma. For comparison, 3 additional cases of invasive micropapillary carcinoma (IMC) and 4 cases of invasive ductal carcinoma (IDC) were studied. Similar results for stromal cells were obtained in all cases. Our results from this preliminary investigation suggest that CD34-positive stromal cells may disappear from the stroma of IMC as well as IDC.}, } @article {pmid15726895, year = {2005}, author = {Matsuzaki, S and Shiba, E and Kobayashi, Y and Kawai, M and Kitamura, K and Nishita, T and Nishio, H and Kobayashi, N}, title = {[Stereotactic vacuum-assisted breast biopsy (Mammotome biopsy) for non-palpable microcalcification on mammography].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {65}, number = {1}, pages = {16-22}, pmid = {15726895}, issn = {0048-0428}, mesh = {Adult ; Aged ; Biopsy/*methods ; Breast/*pathology ; Breast Diseases/pathology ; Breast Neoplasms/pathology ; Calcinosis ; Female ; Humans ; *Mammography ; Middle Aged ; }, abstract = {PURPOSE: The purpose of this study was to assess the benefits of stereotactic vacuum-assisted breast biopsy in patients with non-palpable microcalcification detected on mammography.

METHODS: Between October 2001 and November 2003, stereotactic Mammotome biopsies were performed for 150 microcalcified lesions on mammography using the prone-type stereotactic vacuum-assisted breast biopsy system (Mammotest and Mammovision, Fischer, Denver, USA) . The mammography findings were classified according to the guidelines of The Japan Radiological Society/The Japan Association of Radiological Technologists. Ninety-eight cases were category 3, 38 were category 4, and 14 were category 5.

RESULTS: All cases were determined to be cases of microcalcification by specimen radiography or histology. Complications were negligible. One hundred twenty of the cases were mastopathy, and 30 of them were breast cancer (14 were ductal carcinoma in situ, 7 were ductal carcinoma in situ with microinvasion, and 9 were invasive ductal carcinoma). Twenty-seven breast cancers were diagnosed as category 4 or 5 (51.9%) on mammography. The operative stages of 27 cases were as follows: 7 were stage 0, 17 were stage 1, and 3 were stage 2A. Twenty-four of 27 (88.9%) were early breast cancers.

CONCLUSION: Mammotome biopsy is a safe and useful modality for the histological diagnosis of non-palpable microcalcifications.}, } @article {pmid15723402, year = {2005}, author = {Li, X and Huang, W and Yankeelov, TE and Tudorica, A and Rooney, WD and Springer, CS}, title = {Shutter-speed analysis of contrast reagent bolus-tracking data: Preliminary observations in benign and malignant breast disease.}, journal = {Magnetic resonance in medicine}, volume = {53}, number = {3}, pages = {724-729}, doi = {10.1002/mrm.20405}, pmid = {15723402}, issn = {0740-3194}, support = {R01 EB 00422/EB/NIBIB NIH HHS/United States ; R01 NS 40801/NS/NINDS NIH HHS/United States ; }, mesh = {Breast Diseases/*metabolism ; Breast Neoplasms/metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Contrast Media/*pharmacokinetics ; Female ; Fibroadenoma/*metabolism ; Gadolinium DTPA/*pharmacokinetics ; Humans ; Image Processing, Computer-Assisted ; }, abstract = {The standard pharmacokinetic model applied to contrast reagent (CR) bolus-tracking (B-T) MRI (dynamic-contrast-enhanced) data makes the intrinsic assumption that equilibrium transcytolemmal water molecule exchange is effectively infinitely fast. Theory and simulation have suggested that this assumption can lead to significant errors. Recent analyses of animal model experimental data have confirmed two predicted signature inadequacies: a specific temporal mismatch with the B-T time-course and a CR dose-dependent underestimation of model parameters. The most parsimonious adjustment to account for this aspect leads to the "shutter-speed" pharmacokinetic model. Application of the latter to the animal model data mostly eliminates the two signature inadequacies. Here, the standard and shutter-speed models are applied to B-T data obtained from routine human breast examinations. The signature standard model temporal mismatch is found for each of the three invasive ductal carcinoma (IDC) cases and for each of the three fibroadenoma (FA) cases studied. It is effectively eliminated by use of the shutter-speed model. The size of the mismatch is considerably greater for the IDC lesions than for the FA lesions, causing the shutter-speed model to exhibit improved discrimination of malignant IDC tumors from the benign FA lesions compared with the standard model. Furthermore, the shutter-speed model clearly reveals focal "hot spots" of elevated CR perfusion/permeation present in only the malignant tumors.}, } @article {pmid15719436, year = {2005}, author = {de Mascarel, I and Soubeyran, I and MacGrogan, G and Picot, V and Mathoulin-Pélissier, S}, title = {Immunohistochemically detected lymph node metastases from breast carcinoma: practical considerations about the new American Joint Committee on Cancer classification.}, journal = {Cancer}, volume = {103}, number = {7}, pages = {1319-1322}, doi = {10.1002/cncr.20937}, pmid = {15719436}, issn = {0008-543X}, mesh = {Breast Neoplasms/*classification ; Carcinoma, Ductal, Breast/*classification ; Carcinoma, Lobular/*classification ; Female ; Humans ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Neoplasm Staging ; }, abstract = {BACKGROUND: The authors applied the sixth edition of the American Joint Committee on Cancer (AJCC) classification system to their previously published group of patients with breast carcinoma who had immunohistochemically detected lymph node metastases.

METHODS: The original lymph node-negative slides from 218 patients, including 129 patients with infiltrating duct carcinoma (IDC) and 89 patients with infiltrating lobular carcinoma (ILC), were reviewed and then destained to perform immunohistochemistry. Each tumor cell deposit was measured. Single tumor cells could not counted or measured (because the distance separating the most distant cells could be > 2.0 mm), but they were separated into Class 1 (sparse) and Class 2 (numerous). According to the AJCC classification, isolated tumor cells (ITCs) should be classified as pN0(i+) when they measure < or = 0.2 mm and pN1mi when they measure < or = 2.0 mm but > 0.2 mm.

RESULTS: ITCs were found in 13 IDCs (10%) and in 37 ILCs (41%) and corresponded in IDCs to a single deposit of a few tumor cells that measured < or = 0.2 mm (associated with a single tumor cell in 3 tumors) and were classified as pN0(i+). In ILCs, ITCs corresponded to single tumor cells with an irregular distribution throughout the entire lymph node section (24 ITCs and 13 ITCs in Class 1 and Class 2, respectively) and were difficult to classify.

CONCLUSIONS: The results suggest that there are 2 categories of pN0(i+): measurable tumor cell deposits < or = 0.2 mm, which were found exclusively in IDCs; and nonmeasurable ITCs, which were found in ILCs and rarely in IDCs. The new classification is difficult to apply to ITCs that are detected by immunohistochemistry in ILCs.}, } @article {pmid15717000, year = {2004}, author = {Saleh, EM and Wahab, AH and Elhouseini, ME and Eisa, SS}, title = {Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in human breast carcinoma.}, journal = {Journal of the Egyptian National Cancer Institute}, volume = {16}, number = {1}, pages = {62-68}, pmid = {15717000}, issn = {1110-0362}, abstract = {BACKGROUND: In Egypt, breast cancer ranks number one among the female malignancies. Activation of oncogenes and inactivation of tumor suppressor genes are thought to play an important role in the development and progression of breast cancer.

PURPOSE: The present study is a trial to investigate the role of chromosome 17 in sporadic invasive ductal carcinoma of the breast through detection of LOH for 6 highly polymorphic microsatellite loci, two of which are located at BRCA1 gene (D17S855 and D17S856), one at TP53 gene, one at nm-23 gene and finally two at 17q12-12.3 (D17S183 and D17S250).

MATERIAL AND METHODS: Tissue samples and their corresponding safety margin normal tissues were collected from 25 patients with invasive ductal carcinoma of the breast of grades 2 and 3. LOH was detected for the 6 highly polymorphic microsatellite markers mentioned previously using PCR assay.

RESULTS: The percentage of overall LOH recorded was 68% of the cases examined. The highest LOH recorded in D17S855 and D17S856 (43% and 32% respectively), both markers are located at BRCA1 gene, followed by 32% LOH in nm-23 gene. D17S183 and D17S250, which are localised telomeric and centromeric to BRCA1 gene, showed 24% and 28% LOH, respectively. The lowest percentage of LOH was observed in the TP53 gene (14%). No significant correlation was found between each of the six markers used and lymph node status, grade, or menopausal status. LOH at the nm-23 marker exhibited a significant association with lymph node involvement.

CONCLUSION: It can be concluded from the present study that BRCA1 gene may be involved in carcinogenesis of some sporadic breast cancer cases. Deletion in nm-23 gene is associated with advanced stage of the disease. Finally, another gene located at 17q12-12.3 region may be involved in some sporadic breast cancer cases.}, } @article {pmid15711412, year = {2005}, author = {Cocquyt, V and Van Belle, S}, title = {Lobular carcinoma in situ and invasive lobular cancer of the breast.}, journal = {Current opinion in obstetrics & gynecology}, volume = {17}, number = {1}, pages = {55-60}, doi = {10.1097/00001703-200502000-00010}, pmid = {15711412}, issn = {1040-872X}, mesh = {Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/drug therapy/epidemiology/pathology/*surgery ; Carcinoma in Situ/drug therapy/epidemiology/pathology/*surgery ; Carcinoma, Lobular/drug therapy/epidemiology/pathology/*surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Incidence ; Magnetic Resonance Imaging ; Mastectomy, Radical ; Mastectomy, Segmental ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/epidemiology/etiology/pathology ; Neoplasm Staging ; Preoperative Care ; Prognosis ; Risk Factors ; Sentinel Lymph Node Biopsy ; Survival Rate ; }, abstract = {PURPOSE OF REVIEW: The incidence of lobular carcinoma in situ and invasive lobular carcinoma of the breast is increasing. Recent data suggest that lobular carcinoma in situ is an indolent precursor for breast cancer, rather than a pure risk factor. This could imply free surgical margins become important. The risk of contralateral carcinoma and of multifocality of invasive lobular carcinoma is higher than for invasive ductal carcinoma. Therefore, the need for mastectomy, or even for preventative contralateral mastectomy is questioned. Conventional mammography or ultrasonography cannot always give useful preoperative information about the extent of lobular cancers. The value of dynamic contrast-enhanced magnetic resonance imaging needs to be established for these patients.

RECENT FINDINGS: The risk of invasive carcinoma after lobular carcinoma in situ is increased. Invasive carcinoma is usually located at the index point of lobular carcinoma in situ and is of lobular histology. Dynamic contrast-enhanced magnetic resonance imaging can be useful in the detection and preoperative staging of invasive lobular carcinoma. The risk of local recurrence is high in patients with invasive lobular carcinoma. Mastectomy and breast reconstruction could be an option in selected patients. The response to preoperative chemotherapy is worse for invasive lobular carcinoma compared with invasive ductal carcinoma, with a greater need for rescue mastectomy.

SUMMARY: Lobular carcinoma in situ and invasive lobular carcinoma are different entities from ductal carcinoma in situ and invasive lobular carcinoma. Their biological profile should be studied further in order to make the fine tuning of treatment possible.}, } @article {pmid15701478, year = {2005}, author = {Fauchier, L and Douglas, J and Babuty, D and Cosnay, P and Fauchier, JP}, title = {QT dispersion in nonischemic dilated cardiomyopathy. A long-term evaluation.}, journal = {European journal of heart failure}, volume = {7}, number = {2}, pages = {277-282}, doi = {10.1016/j.ejheart.2004.07.009}, pmid = {15701478}, issn = {1388-9842}, mesh = {Adult ; Aged ; Arrhythmias, Cardiac/*etiology ; Cardiomyopathy, Dilated/complications/*mortality/*physiopathology ; Death, Sudden, Cardiac/*etiology ; Disease-Free Survival ; *Electrocardiography ; Female ; Follow-Up Studies ; Heart Rate/physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Severity of Illness Index ; Ventricular Function, Left/*physiology ; }, abstract = {BACKGROUND: In idiopathic dilated cardiomyopathy (IDC), the predictive value of QT dispersion is still under debate.

AIMS: This study assessed the role of QT dispersion for the long-term risk of cardiac death and of major arrhythmic events in IDC.

METHODS AND RESULTS: In 162 patients with IDC (age 52+/-12 years), the QT interval on a 12-lead ECG was measured manually. QT dispersion was evaluated with QT range and QT standard deviation, for both QT and QTc (Bazett formula). With a follow-up of 53+/-41 months, QT dispersion was not a predictor of cardiac death in univariate or in multivariate analysis, and was of similar value for patients with or without bundle branch block. Using multivariate analysis, increased pulmonary capillary wedge pressure (p=0.003), decreased heart rate variability (Standard deviation of all NN intervals, p=0.01) and non-sustained ventricular tachycardia (NSVT) (p=0.03) were predictors of cardiac death. Sudden death and/or major arrhythmic events were independently predicted by NSVT (p=0.005), decreased heart rate variability (p=0.01) and late ventricular potentials on signal averaged ECG (p=0.02).

CONCLUSION: This study confirms the poor prognostic value of QT dispersion in patients with IDC. Other methods to assess repolarization abnormalities need to be evaluated in such patients.}, } @article {pmid15695074, year = {2005}, author = {Japaze, H and Emina, J and Diaz, C and Schwam, RJ and Gercovich, N and Demonty, G and Morgenfeld, E and Rivarola, E and Gil Deza, E and Gercovich, FG}, title = {'Pure' invasive apocrine carcinoma of the breast: a new clinicopathological entity?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {14}, number = {1}, pages = {3-10}, doi = {10.1016/j.breast.2004.06.003}, pmid = {15695074}, issn = {0960-9776}, mesh = {Adult ; Aged ; Apocrine Glands ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Case-Control Studies ; Female ; Humans ; Middle Aged ; *Neoplasm Invasiveness ; Prognosis ; Survival Analysis ; }, abstract = {Invasive apocrine carcinoma (IAC) of the breast has a similar prognosis to infiltrating ductal carcinoma not otherwise specified (IDC-NOS). The existence of a pure IAC subtype (PIAC) and its possible prognostic implications have not been fully investigated. To this end, pathological inclusion criteria for the diagnosis of PIAC were defined and three pathologists reviewed their slides blind to identify it. To assess its clinical behavior, a case-control evaluation was performed, for which 122 cases were selected. There was 100% agreement among the pathologists on the diagnosis: PIAC was identified in 37 cases and IDC-NOS, in 68, while 17 cases were categorized as complex IAC. The probability of 6-year survival was 0.72 for PIAC and 0.52 for IDC-NOS (P=0.02), and was still better after adjustment for tumor grade and axillary status. PIAC may be a distinct clinicopathological entity with a less aggressive behavior than high-grade IDC-NOS and might be regarded as an independent prognostic factor in early breast cancer.}, } @article {pmid15690336, year = {2005}, author = {Gutmann, EJ and Cates, JM}, title = {Initial diagnosis of breast cancer via cytological examination of a pleural effusion: a rare event facilitated by recognition of an unusual morphological pattern.}, journal = {Diagnostic cytopathology}, volume = {32}, number = {3}, pages = {177-181}, doi = {10.1002/dc.20207}, pmid = {15690336}, issn = {8755-1039}, mesh = {Adenocarcinoma/diagnosis ; Aged ; Biopsy, Needle ; Breast Neoplasms/complications/*diagnosis/pathology ; Carcinoma, Ductal, Breast/complications/*diagnosis/pathology ; Diagnosis, Differential ; Dyspnea/etiology ; Female ; Humans ; Lung Neoplasms/diagnosis ; Pleural Effusion, Malignant/pathology ; Pulmonary Disease, Chronic Obstructive/complications ; }, abstract = {It is uncommon for breast carcinoma to present as a malignant serous effusion. Here, we describe a case in which the initial diagnosis of an occult invasive ductal carcinoma of the breast was made via cytological examination of a pleural effusion. Recognition of a cribriform architecture with intraluminal necrosis and microcalcifications in a cell block preparation was critical in making that diagnosis. To our knowledge, this specific morphological pattern of breast carcinoma in a cell block preparation from an effusion has not been reported previously.}, } @article {pmid15683503, year = {2005}, author = {Lamparter, S and Grimm, W}, title = {Predictive value of high-sensitivity C-reactive protein in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S233-6}, doi = {10.1111/j.1540-8159.2005.00034.x}, pmid = {15683503}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/epidemiology/*etiology ; C-Reactive Protein/*analysis ; Cardiomyopathy, Dilated/*blood/*complications ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; }, abstract = {We analyzed the serum concentrations of high-sensitivity C-reactive protein (hsCRP) at the time of diagnostic cardiac catheterization in 198 patients with idiopathic dilated cardiomyopathy (IDC) to evaluate its prognostic value. Patients were dichotomized according to a median value of hsCRP of 2 mg/dL. Predefined study endpoints over 69 +/- 33 months of follow-up included major arrhythmic events and transplant-free survival. Major arrhythmic events during follow-up occurred in 20 of 98 patients (20%) with low, compared to 22 of 100 patients (22%) with high hsCRP (ns). By multivariate analysis, a depressed left ventricular ejection fraction (LVEF) was the only significant predictor of arrhythmic risk. Death or cardiac transplantation was observed in 36% of patients with high, versus 22% of patients with low hsCRP (P < 0.05). By multivariate analysis, hsCRP and LVEF were independent predictors of transplant-free survival. Thus, in this patient population with IDC, hsCRP had independent prognostic value with regard to transplant-free survival, but did not contribute in the stratification with regard to arrhythmic risk.}, } @article {pmid15683498, year = {2005}, author = {Grimm, W and Christ, M and Maisch, B}, title = {Long runs of non-sustained ventricular tachycardia on 24-hour ambulatory electrocardiogram predict major arrhythmic events in patients with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S207-10}, doi = {10.1111/j.1540-8159.2005.00035.x}, pmid = {15683498}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/diagnosis/etiology ; Cardiomyopathy, Dilated/*complications ; *Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Tachycardia, Ventricular/*diagnosis/etiology ; Time Factors ; }, abstract = {This study examined the prognostic significance of the rate and length of non-sustained (NS) ventricular tachycardia (VT) on 24-hour ambulatory electrocardiograms (ECG) recorded in 343 patients with idiopathic dilated cardiomyopathy (IDC) in the prospective Marburg Cardiomyopathy study. NSVT was defined as >/=3 consecutive ventricular premature beats at >120 bpm. During 52 +/- 21 months of follow-up, major arrhythmic events defined as sustained VT, VF, or sudden cardiac death occurred in 46 of 343 patients (13%). Patients with 3-4 beat runs of NSVT had a similar arrhythmia-free survival as patients without NSVT on baseline 24-hour ambulatory ECG. The incidence of major arrhythmic events during follow-up increased significantly from 2% per year in patients without NSVT, to 5% per year in patients with 5-9 beat runs of NSVT, to 10% per year in patients with >/=10 beat runs of NSVT (P < 0.05). Unlike the length, the rate of NSVT was similar in patients with versus without subsequent major arrhythmic events (163 +/- 23 vs 160 +/- 24 bpm). Thus, the length but not the rate of NSVT on 24-hour ambulatory ECG was a predictor of major arrhythmic events in patients with IDC. The presence of NSVT with >/=10 beat runs on ambulatory ECG was associated with a particularly high risk of major arrhythmic events.}, } @article {pmid15683497, year = {2005}, author = {Grimm, W and Christ, M and Sharkova, J and Maisch, B}, title = {Arrhythmia risk prediction in idiopathic dilated cardiomyopathy based on heart rate variability and baroreflex sensitivity.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {28 Suppl 1}, number = {}, pages = {S202-6}, doi = {10.1111/j.1540-8159.2005.00033.x}, pmid = {15683497}, issn = {0147-8389}, mesh = {Arrhythmias, Cardiac/epidemiology/*etiology ; Baroreflex/*physiology ; Cardiomyopathy, Dilated/*complications/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; }, abstract = {UNLABELLED: This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 +/- 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 +/- 46 vs 109 +/- 45, ns) and BRS (7.9 +/- 5.5 vs 7.7 +/- 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%+/- 7% vs 31%+/- 10%, P < 0.019.

CONCLUSIONS: Neither HRV nor BRS predicted MAE in patients with IDC.}, } @article {pmid15678538, year = {2005}, author = {Sinkus, R and Tanter, M and Catheline, S and Lorenzen, J and Kuhl, C and Sondermann, E and Fink, M}, title = {Imaging anisotropic and viscous properties of breast tissue by magnetic resonance-elastography.}, journal = {Magnetic resonance in medicine}, volume = {53}, number = {2}, pages = {372-387}, doi = {10.1002/mrm.20355}, pmid = {15678538}, issn = {0740-3194}, mesh = {*Algorithms ; Anisotropy ; Breast/*pathology/*physiopathology ; Breast Neoplasms/*diagnosis/*physiopathology ; Computer Simulation ; Elasticity ; Humans ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Models, Biological ; Phantoms, Imaging ; Reproducibility of Results ; Sensitivity and Specificity ; Viscosity ; }, abstract = {MR-elastography is a new technique for assessing the viscoelastic properties of tissue. One current focus of elastography is the provision of new physical parameters for improving the specificity in breast cancer diagnosis. This analysis describes a technique to extend the reconstruction to anisotropic elastic properties in terms of a so-called transversely isotropic model. Viscosity is treated as being isotropic. The particular model chosen for the anisotropy is appealing because it is capable of describing elastic shear anisotropy of parallel fibers. The dependence of the reconstruction on the particular choice of Poisson's ratio is eliminated by extracting the compressional displacement contribution using the Helmholtz-Hodge decomposition. Results are presented for simulations, a polyvinyl alcohol breast phantom, excised beef muscle, and measurements in two patients with breast lesions (invasive ductal carcinoma and fibroadenoma). The results show enhanced anisotropic and viscous properties inside the lesions and an indication for preferred fiber orientation.}, } @article {pmid15671541, year = {2005}, author = {Bhatia, P and Sanders, MM and Hansen, MF}, title = {Expression of receptor activator of nuclear factor-kappaB is inversely correlated with metastatic phenotype in breast carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {11}, number = {1}, pages = {162-165}, pmid = {15671541}, issn = {1078-0432}, support = {AR44904/AR/NIAMS NIH HHS/United States ; }, mesh = {Bone Remodeling ; Bone and Bones/metabolism ; Breast/*metabolism ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; *Gene Expression Regulation, Neoplastic ; Glycoproteins/*metabolism ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Osteoblasts/metabolism ; Osteoclasts/metabolism ; Osteoprotegerin ; Phenotype ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Receptors, Tumor Necrosis Factor/*metabolism ; Time Factors ; }, abstract = {During normal bone remodeling, the receptor activator of nuclear factor-kappaB (RANK) interacts with its ligand RANKL, which is present on pre-osteoclasts, resulting in bone resorption and initiation of new bone formation. When breast cancer metastasizes to bone, normal bone remodeling is disturbed by invasion of tumor cells, resulting in osteolytic lesions. We have studied the expression of both RANK and RANKL in 10 nonneoplastic breast samples, 58 infiltrating ductal carcinoma (IDC), and 43 breast cancer bony metastases (BTM). RANK seemed to be present in all samples tested. However, whereas RANKL expression was observed in 90% of nonneoplastic breast, RANKL expression was only observed in 62% of nonmetastatic IDC, 31% of metastatic IDC, and 2% of osteolytic BTM lesions. This decreased or absent expression of RANKL in the tumor cells may allow RANK, which is normally expressed as a receptor on the cell surface, to target RANKL present on the cell surface of normal osteoblasts and stromal cells of the bone. Stimulation of the normal osteoblasts and stromal cells by the tumor cells may then lead to secondary osteoclastogenesis, resulting in the osteolytic phenotype common to breast metastases.}, } @article {pmid15666042, year = {2004}, author = {Góes, JC and Landecker, A and Lyra, EC and Henríquez, LJ and Góes, RS and Godoy, PM}, title = {The application of mesh support in periareolar breast surgery: clinical and mammographic evaluation.}, journal = {Aesthetic plastic surgery}, volume = {28}, number = {5}, pages = {268-274}, doi = {10.1007/s00266-004-3099-1}, pmid = {15666042}, issn = {0364-216X}, mesh = {Adult ; Breast/abnormalities ; Breast Diseases/*diagnostic imaging/*surgery ; Breast Implantation ; Female ; Humans ; Mammaplasty/*methods ; Mammography/methods ; Middle Aged ; Patient Satisfaction ; Prosthesis Fitting ; Quality of Life ; Surgical Mesh/*statistics & numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Numerous techniques have been described for the treatment of breast hypertrophy and ptosis. Unfortunately, recurrent ptosis after mammaplasty can occur regardless of the technique used. To avoid this problem, different kinds of supporting devices have been described with variable rates of success. However, the true implications of incorporating prosthetic materials into breast surgery have never been clarified. Therefore, surgeons have traditionally been reluctant to apply any kind of prosthetic material to the breast, fearing inflammation, an unfavorable aesthetic outcome, palpable or visible deformities, and interference with the mammographic evaluation of breast cancer. This study analyzed the aesthetic, clinical, and mammographic implications of using mesh as a supportive device in periareolar breast surgery.

METHODS: For this study, 18 patients (mean age, 42 years) with breast hypertrophy, ptosis, or both were managed with the double-skin periareolar mammaplasty technique, with placement of mixed (60% Polyglactine and 40% polyester) mesh. Clinical assessment was performed by three breast surgeons actively working on cancer surveillance who knew that the patients had experienced mesh application. After a mean follow-up period of 30 months, a standard mammogram was performed for each patient and analyzed by both the surgeons and an expert radiologist. The evaluated factors were hyperemia, calcifications, contour irregularities, capsular contraction, thickening or widening of the scar with extrusion of the mesh, and any palpable or hardened areas.

RESULTS: According to the authors' clinical observations, there were no mesh-related abnormalities in the breast; the mesh was not palpable after the operation; and there was no recurrent ptosis. In terms of mammographic imaging, the mesh was visible as a very fine line in the periphery of the breast's parenchyma (measuring 0.2 mm on the lateral views) in three patients (17%). The mesh did not interfere with the visualization and analysis of the breast's parenchyma. In seven patients (39%), benign localized microcalcifications were detected in the breast and no further investigation was performed. In two patients (11%), grouped calcifications were detected and biopsied, with histopathologic analysis demonstrating epithelial hyperplasia with atypia. In two patients (11%), nodules smaller than 1 cm were detected and biopsied, with histopathologic analysis demonstrating a fibroadenoma in one patient and an invasive ductal carcinoma in the other.

CONCLUSIONS: The use of mesh support in breast surgery can enhance the aesthetic results without inducing visible or palpable deformities or mammographic abnormalities. In terms of surveillance mammograms, the presence of the mesh did not interfere with the diagnosis and treatment of minute lesions such as calcifications and small nodules.}, } @article {pmid15657525, year = {2005}, author = {Kijima, Y and Yoshinaka, H and Higuchi, I and Owaki, T and Aikou, T}, title = {A case of amyotrophic lateral sclerosis and breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {12}, number = {1}, pages = {57-59}, doi = {10.2325/jbcs.12.57}, pmid = {15657525}, issn = {1340-6868}, mesh = {Amyotrophic Lateral Sclerosis/*complications ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; }, abstract = {We report a case of breast cancer occurring in a patient with amyotrophic lateral sclerosis (ALS). A 58-year-old Japanese woman diagnosed with ALS 6 years previously noticed a mass in the left breast. We performed a modified radical mastectomy for the mass lesion. Invasive ductal carcinoma without lymph node metastasis was diagnosed. During the operation, she had no worsening of her neurological symptoms. The patient has been cancer-free for 11 months since her operation and no improvement has been seen in her neurological condition. To the best of our knowledge, this is the first case of breast cancer occurring in a patient with ALS in Japan.}, } @article {pmid15656885, year = {2005}, author = {Skalova, A and Ryska, A and Kajo, K and Di Palma, S and Kinkor, Z and Michal, M}, title = {Cystic hypersecretory carcinoma: rare and poorly recognized variant of intraductal carcinoma of the breast. Report of five cases.}, journal = {Histopathology}, volume = {46}, number = {1}, pages = {43-49}, doi = {10.1111/j.1365-2559.2005.02055.x}, pmid = {15656885}, issn = {0309-0167}, mesh = {Aged ; Breast Neoplasms/*diagnosis/metabolism/pathology/surgery/ultrastructure ; Carcinoma in Situ/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/metabolism/pathology/surgery/ultrastructure ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/pathology ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Time Factors ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {AIMS: To report five cases of a rare variant of intraductal carcinoma of the breast, so-called cystic hypersecretory carcinoma. The clinical and pathological characteristics of the lesion are described, along with a review of the literature.

METHODS AND RESULTS: The patients were females aged between 53 and 78 years (average 66.8 years). The size of the lesions ranged between 70 and 80 mm in largest dimension. In two cases, the development of high-grade invasive ductal carcinoma was observed; in one additional case there was recurrence of high-grade in-situ carcinoma after 3 years. This emphasizes the importance of correct diagnosis of this potentially aggressive lesion. Strong over-expression of HER-2/neu protein was observed in three cases, including the two with an invasive component. Protein p53 was variably positive in all cases. Steroid receptor immunohistochemistry yielded variable results with only one case being positive for both oestrogen and progesterone receptors. Interestingly, in most cases (4/5) staining for androgen receptors was observed.

CONCLUSIONS: Cystic hypersecretory ductal carcinoma of the breast is a rare distinctive variant of ductal carcinoma in situ. It has the potential for invasive growth and the development of metastases.}, } @article {pmid15656336, year = {2004}, author = {Hama, Y and Tsuda, H and Sato, K and Hiraide, H and Mochizuki, H and Kusano, S}, title = {Invasive ductal carcinoma of the breast with a large central acellular zone associated with matrix-producing carcinoma.}, journal = {Tumori}, volume = {90}, number = {5}, pages = {498-500}, doi = {10.1177/030089160409000510}, pmid = {15656336}, issn = {0300-8916}, mesh = {Adult ; Biopsy, Needle ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/pathology ; *Extracellular Matrix/pathology ; Female ; Humans ; Metaplasia ; Radiography ; }, abstract = {Matrix-producing carcinoma is a variant of metaplastic carcinoma of the breast that consists of overt carcinoma with direct transition to a cartilagenous and osseous stromal matrix. A clinicopathological association between MPC and high-grade invasive ductal carcinoma with a large central acellular zone has been recently discussed. However, few reports have ever shown the radiological, pathological and immunohistochemical correlation of this unique tumor. We present a case of 27-year-old woman with matrix-producing carcinoma with a large central acellular zone, which was characterized by a large homogeneous hypodense center with well-marginated, ring-like enhancement on contrast enhanced computerized tomography.}, } @article {pmid15651361, year = {2004}, author = {Takeuchi, M and Yamashita, A and Ohgi, K and Kobori, K and Furukawa, T}, title = {[Breast multidetector-row CT with histopathologic correlation].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {64}, number = {8}, pages = {557-563}, pmid = {15651361}, issn = {0048-0428}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; Humans ; Mammography ; Middle Aged ; *Radiographic Image Enhancement ; Tomography, X-Ray Computed/*methods ; }, abstract = {PURPOSE: To evaluate the correlation between multidetector-row CT (MDCT) and histopathologic findings using the same MDCT image as the histopathologic cross-section.

MATERIALS AND METHODS: MDCT with contrast enhancement was performed in 10 patients with breast cancers (8 invasive ductal carcinomas, one invasive lobular carcinoma, and one non-invasive ductal carcinoma). We tried to reconstruct multiplanar reconstructions (MPR) in the same plane as the histopathologic cross-section, and we evaluated the histopathologic findings of the false-positive lesions.

RESULTS: In all cases, we obtained the same MDCT image as the histopathologic cross-section. There were 10 main lesions and 18 other lesions. In the other lesions, we found no false-negative lesions and 11 false-positive lesions. False-positive lesions included periductal fibrosis, cystic change, duct papillomatosis, sclerosing adenosis, fibroadenoma, and others.

CONCLUSION: Using MDCT of the breast, it is possible to obtain good correlation between CT images and histopathologic findings. MDCT is thought to be useful in the evaluation CT findings on the basis of histopathologic evidence.}, } @article {pmid15651359, year = {2004}, author = {Kuwada, T and Tozaki, M and Harada, J}, title = {[Evaluation of enhancement patterns using three-dimensional dynamic contrast-enhanced MR imaging in 209 cases of breast cancer].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {64}, number = {8}, pages = {544-551}, pmid = {15651359}, issn = {0048-0428}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis ; Breast Neoplasms, Male/diagnosis ; Female ; Humans ; *Image Enhancement ; *Imaging, Three-Dimensional ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; }, abstract = {PURPOSE: To evaluate contrast-enhanced patterns using three-dimensional (3D) dynamic MR imaging in 209 cases of breast cancer.

MATERIALS AND METHODS: Three-dimensional dynamic imaging of the breast (1.5-T scanner) was performed in 755 cases. Of 227 breast carcinomas, 209 cases that were histologically confirmed were enrolled in this study. The histological diagnoses included ductal carcinoma in situ (DCIS) (n=12), invasive ductal carcinoma (n=176), mucinous carcinoma (n=10), medullary carcinoma (n=4), invasive lobular carcinoma (n=6), and other (n=1). Tumor size was a mean 24.6 mm in diameter (range, 7-110 mm), including 110 cases of small breast carcinomas (< or = 2 cm). The contrast-enhancement pattern was analyzed from the early phase of 3D-MRI and the post-contrast T1-weighted SE image acquired before the delayed phase of 3D-MRI. The type of peripheral enhancement (PE) was evaluated on the early and delayed phases of 3D-MRI. These enhancement patterns were also compared with the histological findings of small breast carcinomas.

RESULTS: The sensitivity of the 209 cases of breast carcinoma was 99% (207/209) on 3D dynamic MRI. Two hundred six cases (98.6%), including all DCIS, showed strong enhancement on the early phase of 3D MRI. An increased washout pattern showing signal intensity lower than that of fat on post-contrast T1-weighted imaging was noted in 201 cases (96.1%), of which 179 cases (85.6%) showed washout patterns. PE was identified in 63 cases (30.4%) and in 35 of 110 cases of small breast carcinoma (31.8%). Delayed PE following central washout was noted in 65% of 63 cases and 71.4% of 35 cases of small breast carcinoma. Delayed PE was well correlated with marginal fibrosis.

CONCLUSION: Three-dimensional dynamic MRI of the breast was highly sensitive for breast carcinoma. Delayed PE following central washout was considered a specific finding of breast carcinoma. It is important to understand the enhancement patterns of 3D dynamic MRI for excellent specificity of breast carcinomas.}, } @article {pmid15649093, year = {2005}, author = {Thomas, MA and Wyckoff, N and Yue, K and Binesh, N and Banakar, S and Chung, HK and Sayre, J and DeBruhl, N}, title = {Two-dimensional MR spectroscopic characterization of breast cancer in vivo.}, journal = {Technology in cancer research & treatment}, volume = {4}, number = {1}, pages = {99-106}, doi = {10.1177/153303460500400113}, pmid = {15649093}, issn = {1533-0346}, mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*pathology ; Female ; Humans ; *Magnetic Resonance Spectroscopy ; Middle Aged ; Neoplasm Staging ; }, abstract = {The major goal of this work was to characterize invasive ductal carcinoma and healthy fatty breast tissues noninvasively using the classification and regression tree analysis (CART) of 2D MR spectral data. 2D L-COSY spectra were acquired in 14 invasive breast carcinoma and 21 healthy fatty breasts using a GE 1.5 Tesla MRI/MRS scanner equipped with a 2-channel phased-array breast MR coil. The 2D spectra were recorded in approximately 10 minutes using a minimum voxel size of 1 ml without any water suppression technique. For healthy breasts, spectra were acquired from at least one fatty region. 2D L-COSY spectra were recorded in a total of 43 voxels. Five diagonal and six cross peak volumes were integrated and at least eighteen ratios were selected as potential features for the statistical method, namely CART. The 2D L-COSY data showed a significant increase for the majority of these ratios in invasive breast carcinomas compared to healthy fatty tissues. Better accuracy of identifying carcinomas and fatty tissues is reported using CART analysis of different combinations of ratios calculated from the relative levels of water, choline, and saturated and unsaturated lipids. This is a first report on the statistical classification of 2D L-COSY in human breast carcinomas in vivo.}, } @article {pmid15645698, year = {2004}, author = {Glaser, NS and Iden, SB and Green-Burgeson, D and Bennett, C and Hood-Johnson, K and Styne, DM and Goodlin-Jones, B}, title = {Benefits of an insulin dosage calculation device for adolescents with type 1 diabetes mellitus.}, journal = {Journal of pediatric endocrinology & metabolism : JPEM}, volume = {17}, number = {12}, pages = {1641-1651}, doi = {10.1515/jpem.2004.17.12.1641}, pmid = {15645698}, issn = {0334-018X}, mesh = {Adolescent ; Adult ; Child ; Cross-Over Studies ; Diabetes Mellitus, Type 1/complications/*drug therapy ; Dose-Response Relationship, Drug ; Female ; Humans ; Hypoglycemia/complications ; Insulin/*administration & dosage ; Male ; Patient Satisfaction ; }, abstract = {OBJECTIVE: Multiple daily injection insulin regimens (MDI) and continuous subcutaneous insulin infusion (CSII) allow adolescents with type 1 diabetes mellitus (DM) meal flexibility, and may improve metabolic control. The insulin dosage calculations, however, involve ratios of insulin to carbohydrate and corrections for high blood glucose values, and are labor-intensive and prone to error. We evaluated the impact of an insulin dosage calculation device (IDC) on metabolic control, treatment satisfaction, regimen adherence and quality of life in adolescents using MDI or CSII.

RESEARCH DESIGN AND METHODS: We conducted a randomized control trial using the IDC in 83 adolescents on MDI or CSII. At enrollment, patients received training on dosage calculation using either the IDC or conventional methods, and performed sample calculations. At enrollment, 6 months and 12 months, we recorded HbA1c and frequency of hypoglycemia, and patients completed questionnaires assessing treatment satisfaction, regimen adherence and quality of life. After 6 months, patients in the control group were also given the IDC.

RESULTS: We observed a higher frequency of errors with conventional calculations (53-67% incorrect calculations) than with the IDC (25-32% incorrect). At 6 months, there was a trend toward improved HbA1c in the IDC group overall (9.3 vs 8.9, p = 0.07) and a significant improvement in the subset (42%) who used the IDC consistently (9.7 vs 8.8, p = 0.03). There was no change in HbA1c in the control group during this interval (9.0 vs 8.9, p = 0.90). During months 6-12, when both groups were combined, there was a significant increase in HbA1c in patients using the IDC inconsistently or not at all (8.9 vs 9.4, p = 0.005), but no change in HbA1c in those using the IDC consistently (9.1 vs 8.9, p = 0.57). Treatment satisfaction, adherence and quality of life improved throughout the study in both groups.

CONCLUSIONS: Errors in calculation of insulin dosage by adolescents occur frequently. Consistent use of an insulin dosage calculation device may help to improve metabolic control in adolescents using MDI or CSII.}, } @article {pmid15643600, year = {2005}, author = {Maru, D and Middleton, LP and Wang, S and Valero, V and Sahin, A}, title = {HER-2/neu and p53 overexpression as biomarkers of breast carcinoma in women age 30 years and younger.}, journal = {Cancer}, volume = {103}, number = {5}, pages = {900-905}, doi = {10.1002/cncr.20850}, pmid = {15643600}, issn = {0008-543X}, mesh = {Adult ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Receptor, ErbB-2/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: Although p53 and HER-2/neu overexpression are found in 30% of breast carcinomas in women of all ages and are associated with high rates of lymph node metastases, their role in women age < 30 years has not been studied extensively.

METHODS: The institutional breast cancer data base was searched to identify young women (23-30 years) with breast carcinoma. An immunohistochemical analysis was performed to determine estrogen receptor and progesterone receptor expression and p53 and HER-2/neu overexpression. Positive staining for p53 was defined as nuclear staining in > 10% of tumor cells. HER-2/neu membranous staining was graded as 0, 1 (incomplete, faint staining in > 10% of cells), 2 (weak-to-moderate, complete staining in > 10% of cells), or 3 (complete, strong staining in > 10% of cells). Fluorescence in situ hybridization (FISH) was performed on all samples with > or = 2 and > or = 3 results, and only FISH-positive samples were classified as positive. The overexpression was correlated with clinicopathologic features.

RESULTS: Among 44 patients, 1 patient had medullary carcinoma, and 1 had mixed ductal/lobular carcinoma. All remaining patients were diagnosed with invasive ductal carcinoma. The clinical stage was T1 in 5 patients, T2 in 24 patients, T3 in 10 patients, T4 in 4 patients, and unavailable in 1 patient. Positive p53 status was determined in 22 of 44 patients (50%), and positive HER-2/neu status was determined in 18 of 41 patients (44%). Tumors with lymph node metastasis had a significantly greater incidence of HER-2/neu overexpression (P=0.04).

CONCLUSIONS: Frequent overexpression of HER-2/neu and p53 was found in the patient population. HER-2/neu overexpression was associated significantly with lymph node involvement and, thus, may be a marker for aggressive clinical behavior in patients with breast carcinoma age < or = 30 years.}, } @article {pmid15627894, year = {2004}, author = {Yazhou, C and Wenlv, S and Weidong, Z and Licun, W}, title = {Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {25}, number = {5-6}, pages = {290-295}, doi = {10.1159/000081394}, pmid = {15627894}, issn = {1010-4283}, mesh = {Adult ; Aged ; Antigens, CD34/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Female ; *Fibroblasts ; Humans ; Hyperplasia ; Immunohistochemistry ; Middle Aged ; Muscle, Smooth/*cytology ; Prognosis ; Stromal Cells ; }, abstract = {The purpose of this study was to investigate the distribution of CD34-positive fibroblasts and alpha-smooth muscle actin (alpha-SMA)-reactive myofibroblasts in the stroma of benign and malignant breast lesions and, secondly, to determine whether the presence of stromal myofibroblasts is associated with some of the clinicopathological characteristics of patients with invasive ductal carcinoma. The presence of stromal CD34-positive fibroblasts and myofibroblasts was investigated (as defined immunohistochemically) in 8 normal breast tissue samples, 58 invasive ductal carcinomas, 9 ductal carcinomas in situ and 16 specimens with benign lesions of the breast (fibroadenomas, ductal hyperplasias). We further studied the correlations between the presence of stromal myofibroblasts with 7 clinicopathological parameters in 58 invasive ductal carcinomas. The results indicated that the stroma of normal breast tissues contained CD34-positive fibroblasts. All benign breast lesions exhibited stromal CD34-positive fibroblasts. In contrast, the stroma of ductal carcinomas showed a complete loss of CD34-positive fibroblasts. alpha-SMA expression in stromal fibroblasts (myofibroblasts) was not detected in normal tissue samples or benign lesions except in 1 case of fibroadenoma, whereas positive myofibroblasts were found in 44.4% of ductal carcinomas in situ and 56.9% of invasive breast carcinomas. Comparison of clinicopathological parameters between invasive ductal carcinomas with and without stromal myofibroblasts revealed significant differences in lymph node metastasis, high histological grade and high microvessel density. These results suggest that CD34 loss and the presence of myofibroblasts favor the diagnosis of breast carcinoma. In invasive ductal carcinoma, the presence of stromal myofibroblasts correlated significantly with pathological parameters associated with a poor prognosis.}, } @article {pmid15625359, year = {2005}, author = {Cristofanilli, M and Gonzalez-Angulo, A and Sneige, N and Kau, SW and Broglio, K and Theriault, RL and Valero, V and Buzdar, AU and Kuerer, H and Buchholz, TA and Hortobagyi, GN}, title = {Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {23}, number = {1}, pages = {41-48}, doi = {10.1200/JCO.2005.03.111}, pmid = {15625359}, issn = {0732-183X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/*mortality/pathology ; Bridged-Ring Compounds/therapeutic use ; Carcinoma, Ductal/drug therapy/mortality/pathology ; Carcinoma, Lobular/*drug therapy/*mortality/pathology ; Disease-Free Survival ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Neoplasms, Hormone-Dependent/drug therapy/mortality ; Taxoids/therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE: To investigate the impact of histologic type invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) on response to primary chemotherapy (PC) and long-term outcome.

PATIENTS AND METHODS: The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002. One hundred twenty-two patients (12%) had ILC and 912 (88%) had IDC. All patients received anthracycline-based PC, and 346 patients (33.5%) also received a taxane as part of PC. Pathologic complete response (pCR) was defined as no evidence of invasive disease in the breast and axillary lymph nodes.

RESULTS: The median patient age was 48 years (range, 18 to 79 years). Patients with ILC tended to be older (median age, 53 years v 47 years for patients with IDC) and have more hormone-receptor-positive tumors (92% v 62%; P < .001), lower nuclear grade (nuclear grade 3, 16% v 56%; P < .001), and higher stage at diagnosis (10% v 0% with stage IIIB or IIIC disease; P < .001). Patients with ILC were less likely to have a pCR (3% v 15%; P < .001) and had a larger number of involved axillary lymph nodes (41% v 26% had > 3 involved nodes; P = .001). At a median follow-up time of 70 months, ILC patients tended to have longer recurrence-free survival (P = .004) and overall survival (P = .001).

CONCLUSION: ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC. pCR might not be a prognostic indicator for this group of patients.}, } @article {pmid15608061, year = {2004}, author = {Zucchi, I and Mento, E and Kuznetsov, VA and Scotti, M and Valsecchi, V and Simionati, B and Vicinanza, E and Valle, G and Pilotti, S and Reinbold, R and Vezzoni, P and Albertini, A and Dulbecco, R}, title = {Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {101}, number = {52}, pages = {18147-18152}, pmid = {15608061}, issn = {0027-8424}, mesh = {Breast/metabolism ; Breast Neoplasms/*genetics/*pathology ; Carcinoma/genetics/*pathology ; DNA, Complementary/metabolism ; Down-Regulation ; Epithelial Cells/*metabolism ; Epithelium/metabolism ; *Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; In Situ Hybridization ; *Lymphatic Metastasis ; Up-Regulation ; }, abstract = {Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells (approximately 500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer.}, } @article {pmid15605359, year = {2005}, author = {Cox, C and Centeno, B and Dickson, D and Clark, J and Nicosia, S and Dupont, E and Greenberg, H and Stowell, N and White, L and Patel, J and Furman, B and Cantor, A and Hakam, A and Ahmad, N and Diaz, N and King, J}, title = {Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma.}, journal = {Cancer}, volume = {105}, number = {1}, pages = {13-20}, doi = {10.1002/cncr.20738}, pmid = {15605359}, issn = {0008-543X}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma/*pathology/surgery ; Cytodiagnosis/methods ; Female ; Humans ; Intraoperative Period ; Lymphatic Metastasis/*pathology ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND: The current report provides results from a large retrospective analysis of intraoperative imprint cytology performed on axillary sentinel lymph nodes (IIC(N)) removed over the course of 2137 breast surgeries (4905 lymph nodes). It is hoped that these results may serve as benchmarks for those interested in using this technique.

METHODS: The current study included 2078 patients with T1-2 invasive breast carcinoma who underwent sentinel lymph node biopsy (SLNB) and IIC(N). Lymph nodes were bivalved, imprinted, stained with Diff-Quik (Baxter Diagnostics, McGaw Park, IL), and reviewed by a cytopathologist. A positive intraoperative diagnosis led to immediate complete axillary lymph node dissection (CALND). On final pathology, lymph nodes found to be negative on hematoxylin and eosin staining were submitted for cytokeratin staining.

RESULTS: Of the 2137 cases for which SLNB was performed, 673 were found to have positive lymph node status on final pathology. Of these 673 cases, 359 were identified by IIC(N), resulting in a sensitivity rate of 53.3%. The specificity and overall accuracy rates for this technique were 99.5% and 85.0%, respectively. In IDC cases, IIC(N) had a sensitivity rate of 55.5%, compared with 38.7% in ILC cases. Based on these results, the reoperative CALND rate was calculated to be approximately 14.7%, with 54.5% of these reoperative procedures being performed for cases in which lymph nodes positive only for micrometastases were found. Macrometastasis-positive lymph nodes that went undetected by IIC(N) were present in only 154 of the 2137 cases examined (7.2%).

CONCLUSIONS: IIC(N) accurately predicts final lymph node status in 85.0% of patients. Although the accuracy of this technique varies with tumor size and type, IIC(N) remains a time-efficient and cost-effective adjunct to SLNB.}, } @article {pmid15605082, year = {2005}, author = {Bane, AL and Tjan, S and Parkes, RK and Andrulis, I and O'Malley, FP}, title = {Invasive lobular carcinoma: to grade or not to grade.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {18}, number = {5}, pages = {621-628}, doi = {10.1038/modpathol.3800273}, pmid = {15605082}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Cadherins/analysis ; Carcinoma, Lobular/metabolism/*pathology ; Cohort Studies ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; }, abstract = {Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain. The purpose of this study was to correlate histologic grade in invasive lobular carcinoma with known prognostic and predictive markers. All primary resections for invasive mammary carcinomas diagnosed in Mount Sinai Hospital, Toronto, between the years 1996 and 2002 were reviewed (n=1053). Of these cases, 50 were pure invasive lobular carcinoma (incidence 4.7%). The median age at diagnosis was 64 years. These tumors were graded using the Nottingham combined histologic grading system and analyzed for estrogen receptor, progesterone receptor, HER2/neu and E-cadherin expression. Tumor grade was correlated with tumor size (P=0.03), and the American Joint Committee on Cancer nodal status (P=0.05). Assessment of the individual components of grade showed that the mitotic score was highly correlated with tumor size (P=0.02), lymph node positivity (P=0.02) and overall American Joint Committee on Cancer stage (P=0.01). Estrogen receptor and progesterone receptor were highly expressed irrespective of the grade of tumor. HER2/neu protein overexpression and E-cadherin protein expression was absent in all invasive lobular carcinomas studied. We conclude that pure invasive lobular carcinoma is uncommon and occurs predominantly in postmenopausal women. Increasing tumor grade is correlated with median tumor size and the American Joint Committee on Cancer nodal stage, but not correlated with the expression of estrogen receptor, progesterone receptor, E-cadherin or HER2/neu protein overexpression.}, } @article {pmid15604988, year = {2004}, author = {Oyama, T and Koibuchi, Y and McKee, G}, title = {Core needle biopsy (CNB) as a diagnostic method for breast lesions: comparison with fine needle aspiration cytology (FNA).}, journal = {Breast cancer (Tokyo, Japan)}, volume = {11}, number = {4}, pages = {339-342}, doi = {10.1007/BF02968040}, pmid = {15604988}, issn = {1340-6868}, mesh = {Biopsy, Fine-Needle ; *Biopsy, Needle ; Breast Neoplasms/*pathology ; Female ; Humans ; Predictive Value of Tests ; }, abstract = {In Japan, fine needle aspiration biopsy (FNA) of the breast has long been recognized as a useful diagnostic tool, and has been used in many institutions because it provides a rapid, accurate and cost-effective evaluation. However, the use of core needle biopsy (CNB) is increasing, and vacuum assisted biopsy devices have been developed to produce larger specimens for analysis. CNB is useful because the frequency of inadequate specimens is lower than in FNA, and it requires a less invasive procedure than open biopsy. CNB is also more widely used, compared to FNA, because it can provide a more definitive diagnosis of borderline lesions and can be used to distinguish between IDC and ILC. Therefore, the use of CNB with mammographic or ultrasonographic guidance is especially high for non-palpable tumors. FNA is a rapid and non-invasive procedure that is useful for mass lesions. The accuracy of FNA for non-palpable lesions is relatively low, and depends upon the skill of the aspirators, cytoscreeners and cytopathologists involved in the procedure. However, FNA for palpable masses, coupled with a physical and mammographic examination (the so-called triple test) is highly accurate for diagnosis of breast cancer when all three modalities indicate malignancy, and for a benign lesion when all three are negative.}, } @article {pmid15604022, year = {2004}, author = {Vakkila, J and DeMarco, RA and Lotze, MT}, title = {Imaging analysis of STAT1 and NF-kappaB translocation in dendritic cells at the single cell level.}, journal = {Journal of immunological methods}, volume = {294}, number = {1-2}, pages = {123-134}, doi = {10.1016/j.jim.2004.09.007}, pmid = {15604022}, issn = {0022-1759}, mesh = {Antineoplastic Agents/pharmacology ; CD40 Ligand/metabolism ; Cell Communication/physiology ; Cell Nucleus/*physiology ; Cell Separation ; Cell- and Tissue-Based Therapy ; DNA-Binding Proteins/*metabolism ; Dendritic Cells/cytology/*physiology ; Dose-Response Relationship, Drug ; Flow Cytometry ; Humans ; Interferon-gamma/pharmacology ; Interleukin-1/pharmacology ; Interleukin-12/biosynthesis ; K562 Cells ; Killer Cells, Natural/cytology/physiology ; Lipopolysaccharides/pharmacology ; *Microscopy, Fluorescence ; NF-kappa B/*metabolism ; Protein Transport/drug effects/physiology ; Quality Control ; STAT1 Transcription Factor ; Signal Transduction/drug effects/physiology ; Trans-Activators/*metabolism ; }, abstract = {Rapid assessment of immune or stem cells, which are now widely applied in the clinical setting of cancer treatment, is necessary to speed their development and to determine their quality. We have evaluated immature dendritic cells (iDC) by semiautomated imaging cytometry which provides detailed assessment at a single cell level. Nuclear translocation of NF-kappaB was studied by imaging analysis as well as electrophoretic mobility shift assay with an excellent correlation (r=0.981) over a broad range of lipopolysaccharide (LPS) concentrations. Imaging analysis was time saving (5 h vs. 3 days), and required 30- to 100-fold less cells per analysis. Single cell information revealed remarkable heterogeneity between individual iDC and permitted detection of responses to 40 pg/ml of LPS. In IL-1beta/IFNgamma activated iDC, STAT1 responses preceded NF-kappaB responses, and the expression of both was strongly correlated in individual cells (p<0.001). IFNgamma amplified IL-1-induced NF-kappaB responses. NF-kappaB responses to IL-1beta, CD40L, and LPS were donor-dependent (n=7), correlated with the quality of iDC preparations (p=0.002), and IL-12 p70 production (p=0.010). NF-kappaB measurements in iDC within mixed cell cultures (iDC, NK, K562) demonstrated that these strategies are applicable for analyses of complex cell-cell interactions. Imaging analysis is a method that could be valuable for quality control of cell therapy preparations.}, } @article {pmid15592928, year = {2005}, author = {de Jong, RM and Willemsen, AT and Slart, RH and Blanksma, PK and van Waarde, A and Cornel, JH and Vaalburg, W and van Veldhuisen, DJ and Elsinga, PH}, title = {Myocardial beta-adrenoceptor downregulation in idiopathic dilated cardiomyopathy measured in vivo with PET using the new radioligand (S)-[11C]CGP12388.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {32}, number = {4}, pages = {443-447}, pmid = {15592928}, issn = {1619-7070}, mesh = {Adult ; Aged ; Benzimidazoles/*pharmacokinetics ; Carbon Radioisotopes/pharmacokinetics ; Cardiomyopathy, Dilated/*diagnostic imaging/*metabolism ; Down-Regulation ; Female ; Heart/diagnostic imaging ; Humans ; Ligands ; Male ; Middle Aged ; Myocardium/*metabolism ; Positron-Emission Tomography/*methods ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Adrenergic, beta/*metabolism ; Tissue Distribution ; }, abstract = {PURPOSE: The beta-adrenoceptor (beta-AR) plays an important role in heart failure. Recently, the new tracer (S)-[11C]CGP12388 has been developed. It displays excellent properties for investigation of the cardiac beta-ARs in vivo with positron emission tomography (PET). Furthermore, the simple production method allows its use in a routine clinical setting. The aim of this study was to investigate whether decreased myocardial beta-AR density in patients with idiopathic dilated cardiomyopathy (IDC) can be estimated using (S)-[11C]CGP12388 PET.

METHODS: Myocardial beta-AR density was investigated in six patients with IDC and six age-matched healthy controls, using (S)-[11C]CGP12388 PET.

RESULTS: Beta-AR densities of 5.4+/-1.3 pmol/g (mean +/- SD) were observed in patients; these values were significantly lower than those observed in healthy controls (8.4+/-1.5 pmol/g, p<0.005).

CONCLUSION: This study indicates that PET with (S)-[11C]CGP12388 is applicable for the measurement of myocardial beta-AR density in patients. A highly significant reduction in beta-AR density was found in patients with IDC compared with healthy controls.}, } @article {pmid15591718, year = {2004}, author = {Tamiolakis, D and Venizelos, D and Antoniou, C and Tsiminikakis, N and Alifieris, E and Papadopoulos, N}, title = {Breast cancer development in a female with Poland's syndrome.}, journal = {Onkologie}, volume = {27}, number = {6}, pages = {569-571}, doi = {10.1159/000081341}, pmid = {15591718}, issn = {0378-584X}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Female ; Humans ; Poland Syndrome/*pathology ; }, abstract = {BACKGROUND: Poland's syndrome, a rare congenital anomaly characterized by a defect of the pectoralis muscles, has been reported in association with lymphoreticular malignancies and some solid tumors.

CASE REPORT: We report the case of a 53-year-old woman with Poland's syndrome who developed breast cancer in the afflicted ipsilateral hypoplastic breast. FNA cytology revealed a moderately differentiated carcinoma and histology was consistent with a well differentiated invasive ductal carcinoma.

CONCLUSION: Poland's syndrome can be associated with breast cancer so all females with the syndrome should be thoroughly examined for early detection of neoplasia.}, } @article {pmid15583806, year = {2005}, author = {Mylonas, I and Jeschke, U and Shabani, N and Kuhn, C and Friese, K and Gerber, B}, title = {Inhibin/activin subunits (inhibin-alpha, -betaA and -betaB) are differentially expressed in human breast cancer and their metastasis.}, journal = {Oncology reports}, volume = {13}, number = {1}, pages = {81-88}, pmid = {15583806}, issn = {1021-335X}, mesh = {Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/diagnosis/*metabolism/pathology ; Carcinoma, Ductal, Breast/diagnosis/*metabolism/pathology ; Female ; Humans ; Inhibin-beta Subunits/analysis/*metabolism ; Inhibins/analysis/*metabolism ; Lymphatic Metastasis ; Prognosis ; Recurrence ; }, abstract = {Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB). Aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in breast cancer tissue. Paraffin-fixed ductal carcinoma in situ (DCIS; n=7), invasive ductal carcinomas without lymph node metastases (IDC; n=8), infiltrating ductal carcinomas with their lymph node metastases (IDC/LN; n=8), primary ductal carcinomas with their subsequent recurrence (n=7) were analyzed by immunohistochemical means with monoclonal antibodies against inhibin-alpha, -betaA and -betaB subunits. INH-alpha was observed in DCIS (5/7), while its expression was significantly higher in DCIS than IDC (1/7; p<0.05) and IDC/LN (0/8; p<0.005) and recurrent breast cancer tissue (0/7; p<0.005). The INH-betaA subunit was also demonstrated in all DCIS cases with a significantly higher intensity compared to IDC (p<0.05), IDC/LN (p<0.01) and primary carcinoma with subsequent recurrence (p<0.05). INH-betaA expression was significant higher in primary tumors with subsequent recurrence compared to IDC/LN (p<0.05). The metastatic lymph nodes expressed the lowest inhibin-betaA compared to all other groups (p<0.01). INH-betaB was also demonstrated in all mammary carcinoma tissues, but without any statistical differences. The differential expression of INH-alpha in DCIS might suggest a function as a tumor suppressor in breast tissue, suggesting a useful marker for recognizing patients with subsequent risk of developing invasive ductal cancer. The higher INH-betaA expression in DCIS than invasive cancer suggests an important role in mammary carcinogenesis. Interestingly, primary breast tumor with a subsequent recurrence expressed a higher intensity of the inhibin-betaA subunit, suggesting an important role in metastatic pathogenesis, and utilization as a tumor marker. The immunoreactivity of inhibin-betaA was significantly higher in DCIS than invasive ductal carcinomas, suggesting an important role in mammary carcinogenesis. The metastatic lymph nodes expressed lower INH-betaA and -betaB than the primary tumor, which might be the cause of less differentiated and aggressive tumor cells within the primary tumor. Therefore, inhibin/activin subunits might be useful prognostic markers for breast cancer.}, } @article {pmid15578708, year = {2005}, author = {Yankeelov, TE and Rooney, WD and Huang, W and Dyke, JP and Li, X and Tudorica, A and Lee, JH and Koutcher, JA and Springer, CS}, title = {Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology.}, journal = {NMR in biomedicine}, volume = {18}, number = {3}, pages = {173-185}, doi = {10.1002/nbm.938}, pmid = {15578708}, issn = {0952-3480}, support = {P01-CA05826-038A1/CA/NCI NIH HHS/United States ; R01-CA62556/CA/NCI NIH HHS/United States ; R01-EB00422/EB/NIBIB NIH HHS/United States ; R01-HL50139/HL/NHLBI NIH HHS/United States ; R01-NS40801/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; *Algorithms ; Breast Neoplasms/*diagnosis ; Computer Simulation ; *Contrast Media ; Evidence-Based Medicine ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; *Models, Biological ; Multiple Sclerosis/*diagnosis ; Osteosarcoma/*diagnosis ; Reproducibility of Results ; Sample Size ; Sensitivity and Specificity ; }, abstract = {The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (tau(i)) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the tau(i) magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: K(trans), the vascular wall CR transfer rate constant, and v(e), the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's K(trans) and v(e) magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic tau(i) values is the 'shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this 'shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of K(trans). The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model K(trans), v(e), and tau(i) magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.}, } @article {pmid15578430, year = {2005}, author = {Katayama, S and Nakayama, T and Ito, M and Naito, S and Sekine, I}, title = {Expression of the ets-1 proto-oncogene in human breast carcinoma: differential expression with histological grading and growth pattern.}, journal = {Histology and histopathology}, volume = {20}, number = {1}, pages = {119-126}, doi = {10.14670/HH-20.119}, pmid = {15578430}, issn = {0213-3911}, mesh = {Breast/metabolism ; Breast Neoplasms/genetics/*metabolism/physiopathology ; Carcinoma/genetics/*metabolism/physiopathology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Metastasis/genetics ; Proto-Oncogene Mas ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/biosynthesis/*genetics ; Proto-Oncogene Proteins c-ets ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {The proto-oncogene, ets-1, is a transcription factor known to control the expression of a number of genes and has been postulated to play a role in cell growth, differentiation and tumour invasion. We examined 137 cases of breast carcinoma by immunohistochemistry and compared the degree of Ets-1 expression among the different histological types of invasive carcinomas. Ets-1 was not expressed in the normal breast epithelium nor in noninvasive carcinomas. Among the 137 breast carcinoma cases, 104 (83.2%) showed positive staining for the Ets-1 protein. Histologically, invasive ductal carcinomas expressed immunopositivity with intense staining for Ets-1 in the tumour cells. Ets-1 expression correlated with Bloom-Richardson grading in invasive ductal carcinoma (p<0.01). However, there was no correlation between Ets-1 expression and lymph node metastasis, "t" classification or TNM staging. In situ hybridization confirmed the presence of Ets-1 mRNA in breast carcinomas. The expression of Ets-1 mRNA was detected in two of three different kinds of cultured human breast carcinoma cell lines and one of three human breast carcinoma tissues by the reverse transcription polymerase chain reaction method. These findings suggest that ets-1 is overexpressed in ductal cells of the breast that have undergone malignant conversion and that ets-1 is one of the factors associated with tumour growth and histological differentiation of breast carcinomas.}, } @article {pmid15575377, year = {2004}, author = {Zaĭrat'iants, OV and Kolobov, SV and Akopian, IG and Opalenov, KV and Barsanova, TG}, title = {[Expression of estrogen and progesterone receptors and HER-2 by breast cancer cells].}, journal = {Arkhiv patologii}, volume = {66}, number = {5}, pages = {9-12}, pmid = {15575377}, issn = {0004-1955}, mesh = {Adult ; Aged ; Biomarkers, Tumor/biosynthesis ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal/*metabolism/pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Receptor, ErbB-2/*biosynthesis ; Receptors, Estrogen/*biosynthesis ; Receptors, Progesterone/*biosynthesis ; }, abstract = {Breast cell carcinomas removed from 62 women aged from 33 to 74 years were studied immunohistochemically. 24 tumours were of T1N0M0, 5-T1N1M0, 20-T2N0M0, 11-T2N1M0 and 2-T2N0M0. Invasive ductal carcinoma occurred in 59.6%, invasive ductal in 40.4%. Estrogen receptor expression was found in 59.6%, progesterone in 38.7%. Simultaneous expression of these receptors was in 35.5%. Estrogen receptor and progesterone receptor expression were registered in 24.2 and 3.2% cases, respectively. There was neither estrogen nor progesterone expression in 37%. HER-2 expression was observed in 45.2%, the highest being at the age from 50 to 55 years and in invasive ductal carcinoma. Enhancement of estrogen receptor expression was accompanied with lower rate of HER-2 expression. All three antigens expression does not depend on the presence or absence of metastases to the regional lymph nodes.}, } @article {pmid15566931, year = {2004}, author = {Aso, N and Tamura, A and Nasu, M}, title = {Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {94}, number = {11}, pages = {1468-1470}, doi = {10.1016/j.amjcard.2004.07.156}, pmid = {15566931}, issn = {0002-9149}, mesh = {Aged ; Aged, 80 and over ; Biomarkers/*blood ; Cardiomyopathy, Dilated/*pathology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index ; Tenascin/*blood ; Ventricular Dysfunction, Left ; }, abstract = {Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.}, } @article {pmid15565806, year = {2004}, author = {Cayre, A and Cachin, F and Maublant, J and Mestas, D and Penault-Llorca, F}, title = {Does 99mTc-sestamibi uptake discriminate breast tumors?.}, journal = {Cancer investigation}, volume = {22}, number = {4}, pages = {498-504}, doi = {10.1081/cnv-200026388}, pmid = {15565806}, issn = {0735-7907}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism ; Carcinoma, Lobular/metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Neoplasms, Hormone-Dependent/metabolism ; Prognosis ; Radiopharmaceuticals/*metabolism ; Technetium Tc 99m Sestamibi/*metabolism ; }, abstract = {The aim of this work was to investigate 99mTc-sestamibi uptake and histopathological characteristics of breast tumors. Static 99mTc-sestamibi scintimammography (SMM) has been performed in 101 breast tumors (98 patients). SMM were scored from 0 to 4 according to intensity of 99mTc-sestamibi uptake and classified in two groups: SMM with absence or low tumor uptake (0, 1, 2) and SMM with high tumor uptake (3, 4). Tumor histopathological characteristics have been determined on core or excisional biopsy. The 99mTc-sestamibi uptake (low vs. high) correlated to classical prognostic factors: positively with Scarff-Bloom and Richardson (SBR) grade (p < 0.0005), axillary involvement (p < 0.0005), and tumor size (p < 0.0005) and negatively with estrogen receptors (p < 0.001). Fixation of 99mTc-sestamibi in invasive lobular carcinoma was lower than in invasive ductal carcinoma (p < 0.01) despite a similar mean tumor size (28 +/- 14 mm vs. 24 +/- 14 mm). Relations between 99mTc-sestamibi uptake and tumor size, histologic type, and axillary involvement were independent variables also significant in multivariate analysis (p < 0.0005, p < 0.005, p < 0.05, respectively). Moreover, the five-year survival rate was higher when 99mTc-sestamibi breast tumor uptake was low (p < 0.005). This difference is also significant using the Cox model (p < 0.05). Uptake of 99mTc-sestamibi (low vs. high) discriminates breast tumors with different histopathological characteristics and prognosis.}, } @article {pmid15564794, year = {2004}, author = {Lightfoot, HM and Lark, A and Livasy, CA and Moore, DT and Cowan, D and Dressler, L and Craven, RJ and Cance, WG}, title = {Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis.}, journal = {Breast cancer research and treatment}, volume = {88}, number = {2}, pages = {109-116}, doi = {10.1007/s10549-004-1022-8}, pmid = {15564794}, issn = {0167-6806}, support = {CA65910/CA/NCI NIH HHS/United States ; CA83895/CA/NCI NIH HHS/United States ; }, mesh = {Breast Diseases/enzymology/physiopathology ; Breast Neoplasms/*enzymology/*physiopathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/*physiopathology ; Cell Survival ; Cell Transformation, Neoplastic ; Female ; Fibrocystic Breast Disease/enzymology/physiopathology ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; *Gene Expression Profiling ; Humans ; Hyperplasia ; Immunohistochemistry ; Protein-Tyrosine Kinases/*biosynthesis ; Up-Regulation ; }, abstract = {Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in a subset of invasive breast cancers. FAK transmits signals that mediate several functions including tumor cell proliferation, migration, adhesion and survival. We used immunohistochemical techniques to assess FAK expression in patients with fibrocystic disease (FCD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained from 119 patients (12 FCD, 38 ADH, 51 DCIS and 18 IDC). The anti-FAK 4.47 monoclonal antibody was used to detect FAK expression. FAK expression was scored as high (3 or 4 intensity and > or =90% positive cells) or low. The DCIS tissue sections demonstrated high FAK expression in 34/51 (66%) of the sections. High FAK expression was demonstrated in 6/18 (33%) of the IDC tissue sections and 8/38 (21%) of the ADH tissue sections. None (0/12) of the FCD tissues sections stained high for FAK. The pattern of FAK expression in DCIS was significantly higher than ADH (p < 0.0001) and IDC (p = 0.02). We conclude that FAK overexpression in preinvasive, DCIS tumors precedes tumor cell invasion or metastasis, suggesting that FAK may function as a survival signal and be an early event in breast tumorigenesis.}, } @article {pmid15563862, year = {2004}, author = {Apple, SK}, title = {Invasive ductal carcinoma with tissue neutrophilia: a distinct entity?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {13}, number = {6}, pages = {519-521}, doi = {10.1016/j.breast.2004.06.011}, pmid = {15563862}, issn = {0960-9776}, mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neutrophils/*metabolism ; }, abstract = {Infiltrating ductal carcinoma with tissue neutrophilia in the absence of tumor necrosis or clinical evidence of abscess is a rare and unreported phenomenon. A case report is described with cytomorphologic features of FNA and histopathology with immunohistochemical features.}, } @article {pmid15554925, year = {2004}, author = {Mehrotra, S and Chhabra, A and Chakraborty, A and Chattopadhyay, S and Slowik, M and Stevens, R and Zengou, R and Mathias, C and Butterfield, LH and Dorsky, DI and Economou, JS and Mukherji, B and Chakraborty, NG}, title = {Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells.}, journal = {Immunology}, volume = {113}, number = {4}, pages = {472-481}, pmid = {15554925}, issn = {0019-2805}, support = {R01 CA077623/CA/NCI NIH HHS/United States ; CA88059/CA/NCI NIH HHS/United States ; CA77623/CA/NCI NIH HHS/United States ; R01 CA088059/CA/NCI NIH HHS/United States ; R01 CA083130/CA/NCI NIH HHS/United States ; R01 CA079976/CA/NCI NIH HHS/United States ; CA83130/CA/NCI NIH HHS/United States ; CA79976/CA/NCI NIH HHS/United States ; CA61398/CA/NCI NIH HHS/United States ; }, mesh = {Adenoviridae/genetics ; Antigen Presentation/*immunology ; Antigens, Neoplasm/*immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytotoxicity, Immunologic/immunology ; Dendritic Cells/*immunology ; Genetic Vectors ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-10/genetics/*immunology ; Lymphocyte Activation/immunology ; MART-1 Antigen ; Melanoma/immunology ; Neoplasm Proteins/genetics/*immunology ; Transduction, Genetic ; }, abstract = {Dendritic cells (DC) play critical roles in generating an immune response and in inducing tolerance. Diverse microenvironmental factors can 'polarize' DC toward an immunogenic or non-immunogenic phenotype. Among the various microenvironmental factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated in the presence of IL-10 exhibit a profound down-regulation of many genes that are associated with immune activation and show that the IL-10-grown DC are poor stimulators of CD8(+) T cells in a strictly autologous and major histocompatibility complex (MHC) class I-restricted melanoma antigen recognized by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC can efficiently activate the epitope-specific CD8(+) T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen. In addition, we show that the MART-1 protein colocalizes with the MHC class I protein, equally well, in the iDC and in the DC cultured in presence of IL-10 when both DC types are infected with the viral vector. We also show that the vector transduced DC present the MART-1(27-35) epitope for a sustained period compared to the peptide pulsed DC. These data suggest that although DCs generated in the presence of IL-10 tend to be non-immunogenic, they are capable of processing and presenting an antigen when the antigen is synthesized within the DC.}, } @article {pmid15553762, year = {2004}, author = {Sengoku, N and Kuranami, M and Handa, K and Hayashi, K and Enomoto, T and Watanabe, M}, title = {[A case of local advanced breast cancer with multiple lung metastases successfully treated with multimodal therapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {31}, number = {11}, pages = {1927-1929}, pmid = {15553762}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal/*pathology/*therapy ; Combined Modality Therapy ; Docetaxel ; Female ; Humans ; Lung Neoplasms/*secondary/*therapy ; Mastectomy ; Middle Aged ; Palliative Care ; Quality of Life ; Taxoids/administration & dosage ; Trastuzumab ; Ulcer/pathology ; }, abstract = {We report a case of local advanced breast cancer with multiple lung metastases (T4bN2M1) achieving a significant improvement of QOL by multimodal therapy with chemotherapy, antibody therapy, radiation therapy and surgery. The patient was a 47-year-old woman with mental deterioration who had an ulcerative breast cancer with multiple lung metastases. Breast biopsy led to a diagnosis of an invasive ductal carcinoma positive for erbB2 protein expression. She received 6 cycles of tri-weekly docetaxel (60 mg/m2) and weekly trastuzumab. Although metastases in the lung disappeared after chemotherapy, the response of breast ulceration was less satisfactory. Simple mastectomy followed by radiation therapy (50 Gy) to the axilla was performed as a palliative treatment. No signs of recurrence were observed for more than 14 months of treatment by trastuzumab. Multimodal therapy can improve patient QOL and the clinical outcomes in Stage IV local advanced breast cancer.}, } @article {pmid15551757, year = {2004}, author = {Jin, GS and Kondo, E and Miyake, T and Shibata, M and Takashima, T and Liu, YX and Hayashi, K and Akagi, T and Yoshino, T}, title = {Expression and intracellular localization of FKHRL1 in mammary gland neoplasms.}, journal = {Acta medica Okayama}, volume = {58}, number = {4}, pages = {197-205}, doi = {10.18926/AMO/32088}, pmid = {15551757}, issn = {0386-300X}, mesh = {Adult ; Animals ; Antibodies ; Breast Neoplasms/pathology/*physiopathology ; Carcinoma, Ductal, Breast/physiopathology/secondary ; DNA-Binding Proteins/*genetics/immunology/metabolism ; Female ; Fibroadenoma/pathology/physiopathology ; Forkhead Box Protein O1 ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Papilloma, Intraductal/*physiopathology/secondary ; Paraffin Embedding ; Rabbits ; Transcription Factors/*genetics/immunology/metabolism ; }, abstract = {FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.}, } @article {pmid15551732, year = {2004}, author = {Lee, JS and Kim, HS and Kim, YB and Lee, MC and Park, CS and Min, KW}, title = {Reduced PTEN expression is associated with poor outcome and angiogenesis in invasive ductal carcinoma of the breast.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {12}, number = {3}, pages = {205-210}, doi = {10.1097/00129039-200409000-00004}, pmid = {15551732}, issn = {1541-2016}, mesh = {Adult ; Aged ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Microcirculation/pathology ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases/*metabolism ; Prognosis ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {Loss of PTEN expression has been associated with advanced stages of tumor. Tumor angiogenesis is involved in tumor progression. In breast cancer, a high frequency of mutations of the PTEN locus has been reported. However, the prognostic importance of PTEN expression and its correlation with angiogenesis in breast cancer have not been well established. Formalin-fixed, paraffin-embedded tissues from 99 women with a primary diagnosis of invasive ductal carcinoma were evaluated for PTEN expression by immunohistochemical methods. The microvessel density (MVD) was also studied by immunohistochemical labeling of endothelial cells with CD34 antibody. Computerized image analysis was used to evaluate MVD. Reduced PTEN expression was seen in 27.3% of invasive ductal carcinoma. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). Reduced PTEN expression correlated with lymph node status (P < 0.01), tumor grade (P < 0.05), and tumor-node-metastasis (TNM) stage (P < 0.05). There was a statistically significant correlation between reduced PTEN expression and increased MVD (P < 0.05). The mean MVD was higher in reduced PTEN-expressive tumors, irrespective of stage, compared with normal PTEN-expressive tumors with the same stage. On multivariate analysis, only TNM stage and reduced PTEN expression correlated with survival. Our results suggest that reduced PTEN expression may be an independent prognostic indicator in patients with invasive ductal carcinoma. PTEN loss may be associated with increased tumor angiogenesis.}, } @article {pmid15550863, year = {2004}, author = {Kuroda, H and Sakamoto, G and Ohnisi, K and Itoyama, S}, title = {Clinical and pathologic features of invasive micropapillary carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {11}, number = {2}, pages = {169-174}, doi = {10.1007/BF02968297}, pmid = {15550863}, issn = {1340-6868}, mesh = {Adult ; Age of Onset ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma(IMC)of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastases and poor clinical outcome. This histological subtype of breast carcinoma has remained unclear due to the rarity of cases. Many questions exist on the clinicopathological significance of this subtype, especially regarding prognosis.

METHODS: We reviewed all 671 cases of primary breast carcinoma that were surgically resected at our institute between 1990 and 2004. Of these, 27 cases of invasive ductal carcinoma of the breast with a pure or partial micropapillary component were reported. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, presence of lymphatic invasion, and axially lymph node status.

RESULTS: The patients' age at presentation ranged from 31 to 74 years (mean 52.4 years). Tumor size ranged from 0.7 to 10 cm (mean 4 cm). 88.9% (24 of 27) of the cases had lymphatic invasion. Of cases who underwent with axillary dissection, 66.6% (18 of 27) had positive lymph nodes. Clinical follow up data were available for 17 cases with IMC for 1 to 72 months. Among these, 10 patients died from breast carcinoma within 5 years.

CONCLUSION: While our series is too small to make conclusions about the behavior of IMC, the difference in 6-year survival rate between the patients with IMC and those with breast carcinoma in general was statistically significant. Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its poor prognosis and high incidence of lymph node metastases.}, } @article {pmid15550850, year = {2004}, author = {Kuroda, H and Sakamoto, G and Ohnisi, K and Itoyama, S}, title = {Overexpression of Her2/neu, estrogen and progesterone receptors in invasive micropapillary carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {11}, number = {3}, pages = {301-306}, doi = {10.1007/BF02984553}, pmid = {15550850}, issn = {1340-6868}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Papillary/metabolism/*pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; }, abstract = {BACKGROUND: Invasive micropapillary carcinoma (IMC) of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastasis and poor clinical outcome. Furthermore, there has been interest in the prognostic markers related to the biological characteristics of breast carcinoma, such as the status of Her2/neu, estrogen receptor (ER) and progesterone receptor (PgR).

MATERIALS AND METHODS: We reviewed 671 cases of primary breast carcinoma which were surgically resected between 1990 and 2003. Of these, 27 cases of invasive ductal carcinoma of the breast with a pure or partial micropapillary component were reported. Tests for Her2/neu protein, estrogen receptor (ER) and progesterone receptor (PgR) were performed on paraffin sections. The relationship among these markers was analyzed and statistical significance determined by chi-square test.

CONCLUSION: The rate of Her2/neu protein overexpression, ER and PgR status was quite similar to those of common breast carcinomas.}, } @article {pmid15547233, year = {2004}, author = {Kitagawa, K and Sakuma, H and Ishida, N and Hirano, T and Ishihara, A and Takeda, K}, title = {Contrast-enhanced high-resolution MRI of invasive breast cancer: correlation with histopathologic subtypes.}, journal = {AJR. American journal of roentgenology}, volume = {183}, number = {6}, pages = {1805-1809}, doi = {10.2214/ajr.183.6.01831805}, pmid = {15547233}, issn = {0361-803X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasm Invasiveness ; Regression Analysis ; }, abstract = {OBJECTIVE: We sought to determine whether contrast-enhanced MRI could aid in the identification of the histopathologic subtypes of invasive ductal carcinoma.

MATERIALS AND METHODS: We evaluated the contrast-enhanced MR images obtained in 62 women with invasive ductal carcinoma of no special type. The presence or absence of three distinct MRI findings-linear enhancement, a serrated border, and delayed rim enhancement-was evaluated. Classification and regression tree analyses were performed to construct the most efficient algorithm for predicting histopathologic subtype on the basis of dynamic MRI features.

RESULTS: Histopathologic subtypes of the invasive ductal carcinomas were scirrhous carcinoma in 22 patients, solid tubular carcinoma in 14, and papillotubular carcinoma in 26. A lesion with a serrated border was observed in 28 (45.2%) of the 62 patients. Delayed rim enhancement was seen in 23 (37.1%) and linear enhancement in 20 (32.3%). Scirrhous carcinomas were closely associated with a serrated border (20/22 or 90.9%, p < 0.0001). Delayed rim enhancement was frequently observed in solid tubular carcinomas (12/14 or 85.7%, p < 0.0001) but was not typically seen in scirrhous carcinomas (1/22 or 4.5%, p < 0.0001). Linear enhancement showed relatively high prevalence in papillotubular carcinomas (13/26 or 50%) and low prevalence in solid tubular carcinomas (1/22 or 7%, p < 0.02). Histopathologic subtypes of invasive breast carcinoma of no special type could be correctly identified in 47 (75.8%) of 62 lesions using the diagnostic algorithm generated by the classification and regression tree analyses.

CONCLUSION: MRI features showed a close relationship with histopathologic subtypes of invasive ductal carcinoma of no special type. Contrast-enhanced MRI can be a noninvasive diagnostic tool for histopathologic subtypes of invasive breast cancer.}, } @article {pmid15547078, year = {2004}, author = {Radstake, TR and Blom, AB and Slöetjes, AW and van Gorselen, EO and Pesman, GJ and Engelen, L and Torensma, R and van den Berg, WB and Figdor, CG and van Lent, PL and Adema, GJ and Barrera, P}, title = {Increased FcgammaRII expression and aberrant tumour necrosis factor alpha production by mature dendritic cells from patients with active rheumatoid arthritis.}, journal = {Annals of the rheumatic diseases}, volume = {63}, number = {12}, pages = {1556-1563}, pmid = {15547078}, issn = {0003-4967}, mesh = {Antigen-Antibody Complex/immunology ; Arthritis, Rheumatoid/*immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/*immunology ; Gene Expression ; Humans ; RNA, Messenger/genetics ; Receptors, IgG/genetics/*metabolism ; Synovial Membrane/immunology ; Tumor Necrosis Factor-alpha/*biosynthesis ; Up-Regulation/immunology ; }, abstract = {OBJECTIVES: To investigate potential differences in phenotype and behaviour of immature (iDC) and mature dendritic cells (mDC) from patients with RA and healthy subjects.

METHODS: iDC and mDC were derived from blood monocytes of patients with RA and healthy controls following standardised protocols. FACS was used to analyse expression of FcgammaRI, II, and III and molecules to characterise DC. Discrimination between FcgammaRIIa and FcgammaRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFalpha production by iDC and mDC upon FcgammaR dependent stimulation was compared between patients with RA and controls by ELISA.

RESULTS: iDC from patients with active RA but not from patients with inactive RA or healthy controls markedly up regulated FcgammaRII. mDC from patients with active RA also lacked the physiological down regulation of FcgammaRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcgammaRII in RA-especially marked for FcgammaRIIb. FcgammaR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFalpha production by DC from healthy subjects, but significantly decreased TNFalpha by DC from patients with RA. Overlapping expression patterns between FcgammaRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcgammaRIIb.

CONCLUSION: The presence and altered characteristics of DC during active RA suggest that DC help to modulate autoimmunity in RA. Further studies should elucidate the role of local factors in altering the function of DC in RA and in increasing expression of FcgammaRII.}, } @article {pmid15539129, year = {2004}, author = {Perez-Villa, F and Leivas, A and Roig, E and Jiménez, W and Sanz, G}, title = {Adrenomedullin messenger RNA expression is increased in myocardial tissue of patients with idiopathic dilated cardiomyopathy.}, journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}, volume = {23}, number = {11}, pages = {1297-1300}, doi = {10.1016/j.healun.2003.09.002}, pmid = {15539129}, issn = {1053-2498}, mesh = {Adrenomedullin ; Cardiomyopathy, Dilated/*genetics ; Female ; Humans ; Male ; Middle Aged ; Myocardium/chemistry ; Peptides/*genetics ; RNA, Messenger/analysis/*biosynthesis ; }, abstract = {Increased plasma levels of adrenomedullin (ADM) have been reported in patients with congestive heart failure Immunohistochemical ADM has been identified in failing human ventricle, but the gene expression pattern of ADM messenger RNA (mRNA) in myocardial tissue of patients with heart failure has not been elucidated. In this study, gene expression of ADM mRNA (analyzed by northern blot) and tissue concentration of ADM (measured by radioimmunoassay) were assessed in the explanted hearts of 17 patients with idiopathic dilated cardiomyopathy (IDC) and in 7 organ donors with no cardiopathy (controls). Myocardial tissue samples of patients with IDC showed increased ADM mRNA gene expression (p < 0.05) and decreased immunoreactive ADM protein content (p < 0.02) compared with controls.}, } @article {pmid15535846, year = {2004}, author = {Kitayama, J and Shida, D and Sako, A and Ishikawa, M and Hama, K and Aoki, J and Arai, H and Nagawa, H}, title = {Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {6}, pages = {R640-6}, pmid = {15535846}, issn = {1465-542X}, mesh = {Antibodies, Monoclonal/chemistry ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; RNA, Messenger/biosynthesis/genetics ; Receptors, Lysophosphatidic Acid/*biosynthesis/genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor.

METHODS: The relative expression levels of each receptor's mRNA against beta-actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody.

RESULTS: In 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 +/- 426.6 versus 1287.3 +/- 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant (P < 0.05).

CONCLUSION: These findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer.}, } @article {pmid15530488, year = {2005}, author = {Sontag, L and Axelrod, DE}, title = {Evaluation of pathways for progression of heterogeneous breast tumors.}, journal = {Journal of theoretical biology}, volume = {232}, number = {2}, pages = {179-189}, doi = {10.1016/j.jtbi.2004.08.002}, pmid = {15530488}, issn = {0022-5193}, mesh = {Algorithms ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Computer Simulation ; Disease Progression ; Female ; Humans ; Models, Biological ; Neoplasm Invasiveness ; Neoplastic Stem Cells/pathology ; }, abstract = {To better understand the progression of heterogeneous breast cancers, four models of progession pathways have been evaluated. The models describe the progression through the grades of ductal carcinoma in situ (DCIS) 1, 2, and 3, and through the grades of invasive ductal carcinoma (IDC) 1, 2, and 3. The first three pathways, termed linear, nonlinear, and branched, describe DCIS as a progenitor of IDC, and grades of DCIS progressing into grades of IDC. The fourth pathway, termed parallel, describes DCIS and IDC as diverging from a common progenitor and progressing through grades in parallel. The best transition rates for the linear, nonlinear, and branched pathways were sought using a random search in combination with a directed search based on the Nelder-Mead simplex method. Parameter values for the parallel pathway were determined with heuristic graphs. Results of computer simulation were compared with clinically observed frequencies of grades of DCIS and grades of IDC that were reported to occur together in heterogeneous tumors. Each of the four pathways could simulate frequencies that resembled, to varying degrees, the clinical observations. The parallel pathway produced the best correspondence with clinical observations. These results quantify the traditional descriptions in which grades of DCIS are the progenitors of grades of IDC. The results also raise the alternative possibility that, in some tumors with both components, DCIS and IDC may have diverged from a common progenitor.}, } @article {pmid15516615, year = {2004}, author = {Meisamy, S and Bolan, PJ and Baker, EH and Bliss, RL and Gulbahce, E and Everson, LI and Nelson, MT and Emory, TH and Tuttle, TM and Yee, D and Garwood, M}, title = {Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response with in vivo (1)H MR spectroscopy--a pilot study at 4 T.}, journal = {Radiology}, volume = {233}, number = {2}, pages = {424-431}, doi = {10.1148/radiol.2332031285}, pmid = {15516615}, issn = {0033-8419}, support = {CA92004/CA/NCI NIH HHS/United States ; P30 CA77398/CA/NCI NIH HHS/United States ; RR00400/RR/NCRR NIH HHS/United States ; RR08079/RR/NCRR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*drug therapy ; Female ; Gadolinium ; Humans ; Magnetic Resonance Imaging ; *Magnetic Resonance Spectroscopy ; Middle Aged ; *Neoadjuvant Therapy ; Pilot Projects ; }, abstract = {PURPOSE: To determine if changes in the concentration of choline-containing compounds (tCho) from before primary systemic therapy (PST) to within 24 hours after the first treatment enable prediction of clinical response in patients with locally advanced breast cancer.

MATERIALS AND METHODS: Sixteen women with biopsy-confirmed locally advanced breast cancer scheduled to undergo doxorubicin-based PST were recruited. Magnetic resonance (MR) imaging and spectroscopy were performed at 4 T prior to treatment, within 24 hours after the first dose, and after the fourth dose. Lesion size was assessed by using gadolinium-enhanced MR imaging. Lesion tCho concentration was quantified by using single-voxel hydrogen 1 MR spectroscopy. Statistical analysis was performed by using the Pearson correlation coefficient and the Wilcoxon rank sum test.

RESULTS: Fourteen of 16 patients completed the protocol. In one patient, the level of tCho was not measurable because of unfavorable lesion morphology for MR spectroscopy voxel placement. Of the remaining 13 patients, four had inflammatory breast cancer, six had invasive ductal carcinoma, two had invasive lobular carcinoma, and one had mixed invasive ductal and lobular carcinoma. On the basis of the Response Evaluation Criteria in Solid Tumors, eight of 13 patients had an objective response and five had no response. The change in concentration of tCho from baseline to within 24 hours after the first dose of PST showed significant positive correlation with the change in lesion size (R = 0.79, P = .001). Change in tCho concentration within 24 hours after first dose was significantly different between patients with objective response and those with no response (P = .007).

CONCLUSION: These results suggest that the change in tCho concentration between baseline and 24 hours after the first dose of PST can serve as an indicator for predicting clinical response to doxorubicin-based chemotherapy in locally advanced breast cancer.}, } @article {pmid15502381, year = {2004}, author = {Miura, K and Nakagawa, H and Toyoshima, H and Kodama, K and Nagai, M and Morikawa, Y and Inaba, Y and Ohno, Y}, title = {Environmental factors and risk of idiopathic dilated cardiomyopathy: a multi-hospital case-control study in Japan.}, journal = {Circulation journal : official journal of the Japanese Circulation Society}, volume = {68}, number = {11}, pages = {1011-1017}, doi = {10.1253/circj.68.1011}, pmid = {15502381}, issn = {1346-9843}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Infections/complications ; Cardiomyopathy, Dilated/*etiology ; Case-Control Studies ; Education ; *Environment ; Fatigue/complications ; Female ; Humans ; Japan ; Male ; Medical Records ; Middle Aged ; Occupational Exposure ; Odds Ratio ; Risk Factors ; Temperature ; Tobacco Smoke Pollution/adverse effects ; }, abstract = {BACKGROUND: Detailed epidemiological investigations on the relationship of environmental factors, especially occupational and microbiological factors, to the development of idiopathic dilated cardiomyopathy (IDC) are scarce.

METHODS AND RESULTS: A multi-hospital case-control study was conducted in 38 hospitals throughout Japan in order to survey IDC cases and age, sex-matched outpatient controls at each hospital. Crude and adjusted odds ratios (ORs) by various environmental factors were calculated in 135 pairs of cases and controls. Univariate analyses revealed significantly increased ORs for lower education, passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue and history of bacterial infection; in contrast, decreased ORs were associated with a history of rubella and gastroduodenal diseases. Based on multivariate adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13-3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk.

CONCLUSIONS: Some occupational and microbiological factors appear to relate independently to the development of IDC and further investigation is required to establish their respective mechanisms.}, } @article {pmid15499599, year = {2004}, author = {Ranger, GS and Jewell, A and Thomas, V and Mokbel, K}, title = {Elevated expression of cyclooxygenase-2 in breast cancer and ductal carcinoma in situ has no correlation with established prognostic markers.}, journal = {Journal of surgical oncology}, volume = {88}, number = {2}, pages = {100-103}, doi = {10.1002/jso.20142}, pmid = {15499599}, issn = {0022-4790}, mesh = {Breast Neoplasms/*enzymology/pathology/prevention & control ; Carcinoma, Ductal, Breast/*enzymology/pathology/prevention & control ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology/prevention & control ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/therapeutic use ; Female ; Humans ; Isoenzymes/*biosynthesis ; Membrane Proteins ; Precancerous Conditions/enzymology/pathology ; Prognosis ; Prostaglandin-Endoperoxide Synthases/*biosynthesis ; }, abstract = {BACKGROUND AND OBJECTIVES: Elevated expression of cyclooxygenase-2 (COX-2) has been established to be a feature of breast cancer. There has been inconsistency in the literature regarding the precise significance of this-some studies have found no clinicopathological relevance at all, whilst others have concluded COX-2 expression is an important biomarker in invasive disease and pre-cancerous lesions, correlating with poor prognostic features. We studied COX-2 expression in invasive ductal cancer (IDC) specimens and ductal carcinoma in situ (DCIS) in order to clarify these issues.

METHOD: Archival specimens of IDC and DCIS (n = 39) were stained with a polyclonal antibody to COX-2. Results were correlated with recognised clinicopathological parameters.

RESULTS: COX-2 expression occurred in 36.7% of IDCs and 54.5% of DCIS lesions. There was no correlation between increased expression and any clinicopathological features. COX-2 expression did not occur in adjacent non-cancerous tissue (ANCT).

CONCLUSION: We have confirmed that COX-2 expression does occur in invasive cancers, in DCIS, and is not associated with established prognostic markers. The presence of COX-2 expression in DCIS and invasive cancers has positive implications for the future prevention and treatment of breast cancer with COX-2 inhibitors. A large proportion of tumours are, however, COX-2 negative and may be poor candidates for COX-2 suppression.}, } @article {pmid15498363, year = {2004}, author = {Liu, W and Li, WM and Sun, NL}, title = {Relationship between HLA-DQA1 polymorphism and genetic susceptibility to idiopathic dilated cardiomyopathy.}, journal = {Chinese medical journal}, volume = {117}, number = {10}, pages = {1449-1452}, pmid = {15498363}, issn = {0366-6999}, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/*genetics ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; HLA-DQ Antigens/*genetics ; HLA-DQ alpha-Chains ; Humans ; Male ; Middle Aged ; *Polymorphism, Genetic ; }, abstract = {BACKGROUND: Autoimmune mechanisms are likely to participate in the pathogenesis of subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, especially highly polymorphic HLA-DQ genes, play an important role in the activation of immune responses, and thus control the predisposition for or protect from IDC. This study was conducted to investigate the HLA-DQA1 allele polymorphisms in IDC patients and to explore the underlying immunological mechanism and the hereditary susceptibility to IDC.

METHODS: The polymerase chain reaction sequence-specific primers (PCR-SSP) technique was used to analyze the polymorphisms in the second exon of DQA1 in three groups: 72 IDC patients diagnosed according to the criteria of World Health Organization (IDC group); 100 end-stage heart failure patients suffering from a disease of known etiology (HF group); and 100 healthy subjects enrolled for the study during a routine health survey (control group). Patients in the IDC group were stratified according to ejection fraction (EF). Those with EF values were higher than 35% were placed into subgroup 1; subgroup 2 included patients with an EF value of 15% - 35%; and subgroup 3 consisted of those whose EF values less than 15%.

RESULTS: The frequency of HLA-DQA1 *0501 alleles was significantly higher in the IDC group (0.39) than that in the HF group (0.12) and the control group (0.09) (both P < 0.05). Further analysis of the three IDC subgroups showed a higher frequency of DQA1 *0501 among patients with lower EF values (both P < 0.05, compared with subgroups 1 and 2). The frequency of DQA1 *0201 was higher in the control group than that in the IDC group (P < 0.05).

CONCLUSIONS: The HLA-DQA1 *0501 allele confers susceptibility to IDC, while the DQA1 *0201 allele confers protection against it, which indicates that genetic background involved in IDC and heart failure is different. HLA-DQA1 genes are involved in the regulation of specific immune responses by auto- or foreign anti-myocardium antibody.}, } @article {pmid15491965, year = {2004}, author = {Ozdemir, BH and Akcali, Z and Haberal, M}, title = {Hypercholesterolemia impairs angiogenesis in patients with breast carcinoma and, therefore, lowers the risk of metastases.}, journal = {American journal of clinical pathology}, volume = {122}, number = {5}, pages = {696-703}, doi = {10.1309/HW2M-YB5T-VF4A-M0Y4}, pmid = {15491965}, issn = {0002-9173}, mesh = {*Angiogenesis Inhibitors ; Breast Neoplasms/*blood supply/metabolism/*pathology ; Female ; Fibroblast Growth Factor 2/metabolism ; Humans ; *Hypercholesterolemia ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness/*pathology ; Neovascularization, Pathologic/*pathology ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Our aim was to study the effect of hypercholesterolemia on angiogenesis induced by breast carcinoma. Of 51 patients with invasive ductal carcinoma, 28 had hypercholesterolemia and 23 had normocholesterolemia. The intratumoral microvessel density (MVD) was evaluated by using anti-CD31 antibody. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on endothelial and tumor cells was examined and graded semiquantitatively. Patients with normocholesterolemia had a higher MVD (76.4 +/- 8.2) than those with hypercholesterolemia (54.6 +/- 5.1) (P < .01). The risks of recurrence and distant metastasis were higher in patients with normocholesterolemia than in patients with hypercholesterolemia (P < .01). Patients with hypercholesterolemia showed lower expression of endothelial VEGF and bFGF than patients with normocholesterolemia (P < .05 and P < .01, respectively). In addition, tumoral bFGF and VEGF expression showed negative correlation with the presence of hypercholesterolemia (P < .01). We suggest that hypercholesterolemia impairs angiogenesis by suppressing endothelial and tumoral bFGF and VEGF expression and, therefore, lowers the risk of metastases in cases of invasive breast carcinoma.}, } @article {pmid15490785, year = {2004}, author = {Adedoyin, RA and Olaogun, MO and Ukponmwan, OE and Orafidiya, OO}, title = {The effect of histamine iontophoresis on the heart rate and blood pressure of female subjects.}, journal = {African journal of medicine and medical sciences}, volume = {33}, number = {1}, pages = {5-9}, pmid = {15490785}, issn = {0309-3913}, mesh = {Adult ; Arm ; Blood Pressure/*drug effects ; Drug Administration Schedule ; Female ; Gels ; Heart Rate/*drug effects ; Histamine/*administration & dosage ; Humans ; Iontophoresis/adverse effects/*methods ; Sphygmomanometers ; Systole/drug effects ; }, abstract = {The main purpose of this study was to determine the effect of histamine iontophoresis on the Blood Pressure (BP), and heart rate (HR) of female subjects. Twenty apparently healthy female undergraduates of Obafemi Awolowo University, Ile-Ife (average age 24.2 +/- 2.9) participated in the study. An automated electronic sphygmo-manometer that monitors both BP and HR was used to measure the Systolic Blood Pressure(SBP) and diastolic Blood Pressure (DBP) over the left brachial artery. The histamine gel used in this study contained 1 percent histamine dihydro-chloride. The gel was applied to the right biceps brachii and active was applied below the cubital fossa. The current intensity Interrupted Direct Current (IDC) was gradually increased and subjects were instructed to indicate immediately they experienced tingling sensation under the electrode. The same procedure was carried out the second time on the subjects with the same intensity of IDC current but without histamine for each subject. The treatments were administered on different days but within a two-week interval. The cardiovascular response was monitored five minutes before the administration, twenty minutes during the administration and five minutes after the termination of each treatment. Blood Pressure and heart rate did not change significantly from the baseline during the histamine iontophoresis and direct currents treatments (P > 0.05). The findings suggest that the subjects' BP and HR were not affected by histamine iontophoresis during the twenty minutes treatment. It was concluded that local administration of 1 percent histamine dihydrochloride into the subcutaneous tissue of females' right upper arm with the aid of direct current did not appreciably affect the blood pressure and heart rate after 20 minutes of treatment.}, } @article {pmid15486214, year = {2004}, author = {Berg, WA and Gutierrez, L and NessAiver, MS and Carter, WB and Bhargavan, M and Lewis, RS and Ioffe, OB}, title = {Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer.}, journal = {Radiology}, volume = {233}, number = {3}, pages = {830-849}, doi = {10.1148/radiol.2333031484}, pmid = {15486214}, issn = {0033-8419}, mesh = {Adipose Tissue/pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Breast/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging ; Carcinoma in Situ/diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/diagnosis/diagnostic imaging ; Carcinoma, Lobular/diagnosis/diagnostic imaging ; Contrast Media ; False Negative Reactions ; Female ; Humans ; *Magnetic Resonance Imaging/statistics & numerical data ; *Mammography/statistics & numerical data ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; *Palpation/statistics & numerical data ; Prospective Studies ; Sensitivity and Specificity ; *Ultrasonography, Mammary/statistics & numerical data ; }, abstract = {PURPOSE: To prospectively assess accuracy of mammography, clinical examination, ultrasonography (US), and magnetic resonance (MR) imaging in preoperative assessment of local extent of breast cancer.

MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Results of bilateral mammography, US, and contrast-enhanced MR imaging were analyzed from 111 consecutive women with known or suspected invasive breast cancer. Results were correlated with histopathologic findings.

RESULTS: Analysis included 177 malignant foci in 121 cancerous breasts, of which 89 (50%) foci were palpable. Median size of 139 invasive foci was 18 mm (range, 2-107 mm). Mammographic sensitivity decreased from 100% in fatty breasts to 45% in extremely dense breasts. Mammographic sensitivity was highest for invasive ductal carcinoma (IDC) in 89 of 110 (81%) cases versus 10 of 29 (34%) cases of invasive lobular carcinoma (ILC) (P < .001) and 21 of 38 (55%) cases of ductal carcinoma in situ (DCIS) (P < .01). US showed higher sensitivity than did mammography for IDC, depicting 104 of 110 (94%) cases, and for ILC, depicting 25 of 29 (86%) cases (P < .01 for each). US showed higher sensitivity for invasive cancer than DCIS (18 of 38 [47%], P < .001). MR showed higher sensitivity than did mammography for all tumor types (P < .01) and higher sensitivity than did US for DCIS (P < .001), depicting 105 of 110 (95%) cases of IDC, 28 of 29 (96%) cases of ILC, and 34 of 38 (89%) cases of DCIS. In anticipation of conservation or no surgery after mammography and clinical examination in 96 breasts, additional tumor (which altered surgical approach) was present in 30. Additional tumor was depicted in 17 of 96 (18%) breasts at US and in 29 of 96 (30%) at MR, though extent was now overestimated in 12 of 96 (12%) at US and 20 of 96 (21%) at MR imaging. After combined mammography, clinical examination, and US, MR depicted additional tumor in another 12 of 96 (12%) breasts and led to overestimation of extent in another six (6%); US showed no detection benefit after MR imaging. Bilateral cancer was present in 10 of 111 (9%) patients; contralateral tumor was depicted mammographically in six and with both US and MR in an additional three. One contralateral cancer was demonstrated only clinically.

CONCLUSION: In nonfatty breasts, US and MR imaging were more sensitive than mammography for invasive cancer, but both MR imaging and US involved risk of overestimation of tumor extent. Combined mammography, clinical examination, and MR imaging were more sensitive than any other individual test or combination of tests.}, } @article {pmid15482568, year = {2004}, author = {Chen, WY and Chen, CS and Chen, HC and Hung, YJ and Chu, JS}, title = {Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal carcinoma.}, journal = {Pathology international}, volume = {54}, number = {10}, pages = {781-786}, doi = {10.1111/j.1440-1827.2004.01755.x}, pmid = {15482568}, issn = {1320-5463}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology/therapy ; Carcinoma, Ductal, Breast/metabolism/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Cystadenocarcinoma, Mucinous/metabolism/*pathology/therapy ; Female ; Humans ; Mastectomy, Radical ; Mucins/metabolism ; Neoplasm Staging ; Neoplasms, Multiple Primary/metabolism/*pathology/therapy ; Treatment Outcome ; }, abstract = {A recently described and rare variant of breast carcinoma, mucinous cystadenocarcinoma (MCA), is reported in a 65-year-old post-menopausal woman. She presented with a gradually enlarged breast tumor. A well-circumscribed tumor measuring about 3 cm in diameter was noted in the mammographic and ultrasonographic examinations. The mammographic and ultrasonographic findings were indistinguishable from more common mucinous carcinoma (colloid carcinoma) of the breast. The gross appearance of the tumor was well-defined and cystic, consisting of abundant transparent to bloody mucin, as well as whitish solid parts. Microscopically, the tumor was characterized by abundant extracellular and intracellular mucin. It looked like a mucinous cystic neoplasm of the ovary and pancreas. Particularly, few microscopic foci of ordinary intermediate-grade infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) were observed around the main lesion in this case. A transition from ordinary DCIS to MCA in situ was found. It might indicate MCA derives from a metaplasia process of ordinary DCIS. MCA can be easily differentiated from mucinous carcinoma by quite different histologic and immunohistochemical findings. According to the previously reported and present cases, MCA of the breast more commonly affects elderly women and has a relatively favorable prognosis.}, } @article {pmid15480266, year = {2004}, author = {Frachon, S and Pasquier, D and Treilleux, I and Seigneurin, D and Ringeisen, F and Rosier, P and Bolla, M and Boutonnat, J}, title = {[Breast carcinoma with predominant neuroendocrine differentiation].}, journal = {Annales de pathologie}, volume = {24}, number = {3}, pages = {278-283}, doi = {10.1016/s0242-6498(04)93966-1}, pmid = {15480266}, issn = {0242-6498}, mesh = {Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/*secondary ; Breast Neoplasms/chemistry/drug therapy/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Carcinoma, Neuroendocrine/chemistry/pathology/*secondary ; Cell Differentiation ; Chemotherapy, Adjuvant ; Chromogranin A ; Chromogranins/analysis ; Combined Modality Therapy ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Proteins/analysis ; Neoplastic Stem Cells/*pathology ; Neural Cell Adhesion Molecules/analysis ; Radiotherapy, Adjuvant ; Sternum/chemistry/*pathology ; Synaptophysin/analysis ; }, abstract = {Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.}, } @article {pmid15478975, year = {2004}, author = {Mischi, M and Kalker, TA and Korsten, EH}, title = {Contrast echocardiography for pulmonary blood volume quantification.}, journal = {IEEE transactions on ultrasonics, ferroelectrics, and frequency control}, volume = {51}, number = {9}, pages = {1137-1147}, doi = {10.1109/tuffc.2004.1334846}, pmid = {15478975}, issn = {0885-3010}, mesh = {*Algorithms ; *Blood Flow Velocity ; Blood Volume/*physiology ; Blood Volume Determination/*methods ; Computer Simulation ; Contrast Media ; Echocardiography/instrumentation/*methods ; Image Enhancement/methods ; Image Interpretation, Computer-Assisted/*methods ; Indicator Dilution Techniques ; Models, Cardiovascular ; Phantoms, Imaging ; Pulmonary Circulation/*physiology ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {Pulmonary blood volume quantification is important both for diagnosis and for monitoring of the circulatory system. It requires employment of transpulmonary indicator dilution techniques, which are very invasive due to the need for double catheterization. This paper presents a new minimally invasive technique for blood volume quantification. An ultrasound contrast agent bolus is injected peripherally and detected by an ultrasound transducer in the central circulation. Several echocardiographic views permit simultaneous detection of contrast in different cardiac cavities and central vessels, and acoustic backscatter measurements produce multiple indicator dilution curves (IDCs). Contrast mean-transit-time differences are derived from the IDC analysis and multiplied times cardiac output for the assessment of blood volumes between different detection sites. For pulmonary blood volume estimates, the right ventricle and the left atrium IDCs are measured. The mean transit time of the IDC is estimated by specific modelling. The Local Density Random Walk and the First Passage Time models were tested for IDC interpolation and interpretation. The system was validated in vitro for a wide range of flows. The results show very accurate volume measurements. The volume estimate determination coefficient is greater than 0.999 for both model fits. A preliminary study in patients shows promising results.}, } @article {pmid15474428, year = {2004}, author = {Romero, L and Klein, L and Ye, W and Holmes, D and Soni, R and Silberman, H and Lagios, MD and Silverstein, MJ}, title = {Outcome after invasive recurrence in patients with ductal carcinoma in situ of the breast.}, journal = {American journal of surgery}, volume = {188}, number = {4}, pages = {371-376}, doi = {10.1016/j.amjsurg.2004.06.034}, pmid = {15474428}, issn = {0002-9610}, mesh = {Breast Neoplasms/*mortality ; Carcinoma in Situ/*mortality ; Carcinoma, Ductal, Breast/*mortality ; Female ; Follow-Up Studies ; Humans ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/*mortality ; Prospective Studies ; Survival Rate ; Time Factors ; }, abstract = {BACKGROUND: Local recurrence is used as a marker of treatment failure for patients with ductal carcinoma in situ (DCIS). As follow-up lengthens, distant recurrence, breast cancer-specific survival (BCSS), and overall survival must be monitored.

METHODS: A prospective database was used to analyze 1031 patients with DCIS. Patients having invasive recurrence after DCIS treatment were compared with patients having infiltrating ductal carcinoma (IDC). End points included distant recurrence, BCSS, and overall survival.

RESULTS: Overall, patients with DCIS had a BCSS of 99%. BCSS was 85% for patients with invasive recurrences. DDFS in this group was 80%. Stage I IDC patients had a BCSS of 91%, whereas it was 38% in those with stage I IDC and invasive recurrences.

CONCLUSIONS: Most patients with DCIS that recur can be salvaged. For the small subgroup of patients who recur with invasive breast cancer, survival is similar to that of patients with stage IIA IDC.}, } @article {pmid15472858, year = {2004}, author = {DeJesus, E and Herrera, G and Teofilo, E and Gerstoft, J and Buendia, CB and Brand, JD and Brothers, CH and Hernandez, J and Castillo, SA and Bonny, T and Lanier, ER and Scott, TR and , }, title = {Abacavir versus zidovudine combined with lamivudine and efavirenz, for the treatment of antiretroviral-naive HIV-infected adults.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {39}, number = {7}, pages = {1038-1046}, doi = {10.1086/424009}, pmid = {15472858}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; Aged ; Alkynes ; Anti-HIV Agents/adverse effects/therapeutic use ; Benzoxazines ; CD4 Lymphocyte Count ; Cyclopropanes ; Dideoxynucleosides/adverse effects/*therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; HIV Infections/*drug therapy ; Humans ; Lamivudine/adverse effects/*therapeutic use ; Male ; Middle Aged ; Oxazines/adverse effects/*therapeutic use ; RNA, Viral/blood ; Zidovudine/adverse effects/*therapeutic use ; }, abstract = {BACKGROUND: Zidovudine, lamivudine, and efavirenz comprise a highly effective and well-tolerated triple regimen for antiretroviral-naive patients. Evaluating other unique nucleoside reverse-transcriptase inhibitor (NRTI) combinations for long-term viral suppression is desirable.

METHODS: This multicenter, randomized, double-blind noninferiority clinical trial compared the efficacy and safety of abacavir with that of zidovudine plus lamivudine and efavirenz in 649 antiretroviral-naive HIV-infected patients. The primary objective was a comparison of proportions of patients achieving plasma HIV-1 RNA levels
RESULTS: At study week 48, 70% of patients in the abacavir group, compared with 69% in the zidovudine group, maintained confirmed plasma HIV-1 RNA levels of
CONCLUSION: Abacavir provided an effective and durable antiretroviral response that was noninferior to zidovudine, when combined with lamivudine and efavirenz.}, } @article {pmid15467428, year = {2004}, author = {Hussein, MR and Ismael, HH}, title = {Alterations of p53, Bcl-2, and hMSH2 protein expression in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas in the upper Egypt.}, journal = {Cancer biology & therapy}, volume = {3}, number = {10}, pages = {983-988}, doi = {10.4161/cbt.3.10.1136}, pmid = {15467428}, issn = {1538-4047}, mesh = {Adult ; Breast/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; DNA-Binding Proteins/*metabolism ; Egypt ; Female ; Humans ; Immunoenzyme Techniques ; MutS Homolog 2 Protein ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND: Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (Bcl-2) and housekeeping genes [human MutS homologue-2 (hMSH2)]. We hypothesized that mammary carcinogenesis involves interactions among p53, Bcl-2 and hMSh2 proteins. In the Upper Egypt, the clinicopathologic features and genetic changes during mammary carcinogenesis are unknown.

METHODS: To test our hypothesis and to examine these issues, 53 mastectomy specimens, each entailing normal breast, benign proliferative breast disease (BPBD), duct carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were immunostained for p53, Bcl-2 and hMSH2 protein expression.

RESULTS: The average age incidence of ductal carcinomas was 43.2 +/- 7.06 years. The tumors were common in the left than right side (1.2:1, respectively, p > 0.05). Infiltrating ductal carcinoma of non-specific type was the most common histologic type. Examination of the average weighted scores in the normal breast, BPBD, DCIS and IDC, respectively, showed: (1) significant upregulation of p53 proteins (0.00 +/- 0.00, 0.00 +/- 0.00, 6.25 +/- 2.42, 6.62 +/- 2.15, p = 0.001), (2) insignificant downregulation of Bcl-2 (6.67 +/- 1.33, 5.17 +/- 2.20, 4.79 +/- 2.27 and 4.42 +/- 2.83, p = 0.37), and (3) significant downregulation of hMSH2 (11.3 +/- 0.75, 10.70 +/- 1.27, 7.11 +/- 1.50 and 7.0 +/- 1.33, p = 0.0006). There were insignificant negative correlations between p53 and both Bcl-2 (r = -0.20, p > 0.05) and hMSH2 (r = -0.15, p > 0.05) protein expression.

CONCLUSIONS: In the Upper Egypt: (1) breast cancer had similar clinicopathologic features to those in the high risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during mammary carcinogenesis.}, } @article {pmid15466187, year = {2004}, author = {Zhang, J and Shridhar, R and Dai, Q and Song, J and Barlow, SC and Yin, L and Sloane, BF and Miller, FR and Meschonat, C and Li, BD and Abreo, F and Keppler, D}, title = {Cystatin m: a novel candidate tumor suppressor gene for breast cancer.}, journal = {Cancer research}, volume = {64}, number = {19}, pages = {6957-6964}, doi = {10.1158/0008-5472.CAN-04-0819}, pmid = {15466187}, issn = {0008-5472}, support = {CA36481/CA/NCI NIH HHS/United States ; CA91785/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*genetics/metabolism/pathology ; Cell Division/physiology ; Cell Line, Tumor ; Cystatin M ; Cystatins/biosynthesis/*genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Liver Neoplasms, Experimental/pathology/secondary ; Lung Neoplasms/pathology/secondary ; Mice ; Mice, Inbred ICR ; Mice, SCID ; Neoplasm Staging ; Transfection ; }, abstract = {The contribution of pericellular proteolysis to tumor progression is well documented. To better understand protease biology and facilitate clinical translation, specific proteolytic systems need to be better defined. In particular, the precise role of endogenous protease inhibitors still needs to be deciphered. We reported previously that cystatin M, a potent endogenous inhibitor of lysosomal cysteine proteases, significantly suppressed in vitro cell proliferation, migration, and Matrigel invasion. Here, we show that scid mice orthotopically implanted with breast cancer cells expressing cystatin M show significantly delayed primary tumor growth and lower metastatic burden in the lungs and liver when compared with mice implanted with mock controls. The incidence of metastasis, however, appeared to be unaltered between the cystatin M group and the control group. Experimental metastasis assays suggest that cystatin M suppressed tumor cell proliferation at the secondary site. By using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction, we found consistent expression of cystatin M in normal human breast epithelial cells, whereas expression was decreased by 86% in invasive ductal carcinoma (IDC) cells of stage I to IV patients. Complete loss of expression of cystatin M was observed in two of three IDCs from stage IV patients. Immunohistochemical studies confirmed that expression of cystatin M in IDCs was partially or completely lost. We propose cystatin M as a novel candidate tumor suppressor gene for breast cancer.}, } @article {pmid15459534, year = {2004}, author = {Tomasini, C and Grassi, M and Pippione, M}, title = {Cutaneous angiosarcoma arising in an irradiated breast. Case report and review of the literature.}, journal = {Dermatology (Basel, Switzerland)}, volume = {209}, number = {3}, pages = {208-214}, doi = {10.1159/000079891}, pmid = {15459534}, issn = {1018-8665}, mesh = {Aged ; Breast Neoplasms/*radiotherapy ; Female ; Hemangiosarcoma/*etiology/pathology ; Humans ; Neoplasms, Radiation-Induced/*etiology/pathology ; Radiotherapy/adverse effects ; Skin Neoplasms/*etiology/pathology ; }, abstract = {Angiosarcoma (AS) is a rare, aggressive tumour of endothelial origin occurring in various clinical settings, including idiopathic AS on the head and neck in elderly people, lymphoedema-associated AS, post-irradiation AS, soft-tissue AS, and various others. Despite the widespread use of radiation therapy in the treatment of breast carcinoma, AS developing in the wake of a radiation therapy is extremely infrequent. Although there is little doubt that radiation in therapeutic doses can induce sarcomas, quantification of that risk is complicated by many variables, among them chronic lymphoedema. We describe a 70-year-old woman in generally good health who presented with a 2-year history of a maculo-papular eruption on the skin of her right breast. There was no lymphoedema of the thoracic area. The lesions developed 3 years after she had undergone ipsilateral quadrantectomy for an invasive ductal carcinoma followed by 25 tangent field radiotherapy sessions on the breast. The oncological follow-up did not disclose local recurrence of the tumour or metastases of breast carcinoma. Histopathologic examination of a papule was diagnostic for AS. In addition, signs of chronic radiation dermatitis were found in the biopsy specimens. The patient underwent monthly cycles of chemotherapy with intravenous doxorubicin with partial remission of the affected area after 24 months, followed by the occurrence of liver metastases and exitus 30 months after diagnosis. From the review of the literature, it appears that post-irradiation mammary AS mainly affects women over 60 who have undergone breast-sparing surgery and that it is usually associated with axillary lymphadenectomy. Whereas the role of lymphoedema does not seem relevant to the pathogenesis of this malignancy, the association with chronic radiation dermatitis in our case reinforces the supposed role of radiation in the development of this tumour. Onset of AS should be taken into consideration when treating patients who develop multiple lesions on the skin above the irradiated area, even many years after the therapy.}, } @article {pmid15455946, year = {2004}, author = {Ishikawa, H and Kimura, T and Oya, A and Kamitani, A and Inoue, Y and Suzuki, K and Akira, M and Hayashi, S and Kawahara, M and Okada, Z and Kimura, K and Iuchi, K and Sakatani, M}, title = {[Application of interlocking detachable coil (IDC) in superselective bronchial artery embolization].}, journal = {Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society}, volume = {42}, number = {8}, pages = {730-736}, pmid = {15455946}, issn = {1343-3490}, mesh = {Aged ; *Bronchial Arteries ; Embolization, Therapeutic/*methods ; Hemoptysis/prevention & control/*therapy ; Humans ; Metals ; Middle Aged ; Plastics ; Secondary Prevention ; Time Factors ; Treatment Outcome ; }, abstract = {Bronchial artery embolization (BAE) is almost the only effective nonsurgical treatment for massive hemoptysis. Metallic coils with plastic fibers are widely used as embolic materials. We have introduced an interlocking detachable coil (IDC) for BAE. IDC is a mechanically detachable coil, allowing the operator to seek the ideal shape until its final release. We compared hemoptysis patients treated with conventional metallic coils (24 patients, non-IDC group) with those treated with conventional coils and IDCs (26 patients, IDC group). The hemoptysis rate after three months is significantly lower in the IDC group than in the non-IDC group (7.7% vs. 16.3%, p = 0.035 Fisher's exact method). Total procedure time (in staged or repetitive BAE cases, procedure times are added together) is significantly shorter in the IDC group than in the non-IDC group (3.4 +/- 1.4 hours vs. 4.4 +/- 2.5 hours, p = 0.040 unpaired t-test). IDC is a useful device for BAE. This is the first-ever report documenting the usefulness of IDC for BAE.}, } @article {pmid15455373, year = {2005}, author = {Yuan, Y and Liu, H and Sahin, A and Dai, JL}, title = {Reactivation of SYK expression by inhibition of DNA methylation suppresses breast cancer cell invasiveness.}, journal = {International journal of cancer}, volume = {113}, number = {4}, pages = {654-659}, doi = {10.1002/ijc.20628}, pmid = {15455373}, issn = {0020-7136}, support = {R01CA100278/CA/NCI NIH HHS/United States ; }, mesh = {Antimetabolites, Antineoplastic/pharmacology ; Azacitidine/*analogs & derivatives/pharmacology ; Breast/metabolism ; Breast Neoplasms/genetics/*prevention & control ; Carcinoma, Ductal/genetics/prevention & control ; Carcinoma, Intraductal, Noninfiltrating/genetics/prevention & control ; Cell Proliferation/drug effects ; *DNA Methylation ; DNA Modification Methylases/antagonists & inhibitors ; Decitabine ; Enzyme Precursors/*antagonists & inhibitors/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Intracellular Signaling Peptides and Proteins ; Neoplasm Invasiveness/*prevention & control ; Phenotype ; Protein-Tyrosine Kinases/*antagonists & inhibitors/*genetics/metabolism ; Stilbenes/pharmacology ; Syk Kinase ; }, abstract = {The gene product of spleen tyrosine kinase (SYK) has been implicated in the suppression of breast cancer invasion. We previously reported that SYK expression is lost in a subset of breast cancer; primarily by methylation-mediated gene silencing. In our study, we explored the possibility of using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (AZA), to suppress breast cancer cell invasion by restoring SYK expression. We found that AZA treatment reestablished the expression of SYK(L) that was accompanied by suppression of the invasion capacity of SYK-negative cells. This invasion inhibition was not due to global cellular toxicity since this treatment did not affect overall cell proliferation. This decreased invasiveness by AZA treatment was diminished by piceatannol, a SYK inhibitor, suggesting that SYK play a significant role in AZA-inducible invasion suppression. SYK promoter hypermethylation was found infrequent in pathologically normal mammary tissues or benign lesions (<5%). In contrast, SYK methylation was frequently identified in ductal carcinoma in situ (approximately 45%) and invasive ductal carcinoma (47% in node-negative and 40% in node-positive cases), indicating that the hypermethylation of SYK occurs at a stage prior to the development of invasion phenotypes. All these results suggested a potential use of SYK methylation as a valuable biomarker to detect early cancerous lesions and support the use of AZA as a new reagent to the management of advanced breast cancer.}, } @article {pmid15454252, year = {2004}, author = {Ainsworth, PD and Winstanley, JH and Pearson, JM and Bishop, HM and Garrod, DR}, title = {Protein kinase C alpha expression in normal breast, ductal carcinoma in situ and invasive ductal carcinoma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {40}, number = {15}, pages = {2269-2273}, doi = {10.1016/j.ejca.2004.06.027}, pmid = {15454252}, issn = {0959-8049}, mesh = {Breast/*enzymology ; Breast Neoplasms/*enzymology ; Carcinoma, Ductal, Breast/*enzymology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology ; Female ; Humans ; Immunohistochemistry ; Neoplasm Proteins/*metabolism ; Protein Kinase C/*metabolism ; Protein Kinase C-alpha ; }, abstract = {The purpose of this study was to determine if Protein Kinase C alpha (PKC alpha) is altered in expression or localisation in normal breast, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). We obtained 14 mixed cases of invasive ductal carcinoma (IDC) and DCIS, 36 pure DCIS cases and 25 cases of normal breast. The sections were stained immunohistochemically for PKC alpha expression. Staining was cytoplasmic. The results showed a progressive reduction in staining intensity from normal breast to invasive ductal carcinoma. The staining pattern was heterogeneous in the cytoplasm of DCIS and IDC, but homogeneous in the cytoplasm of normal breast ductal epithelium. Interestingly, mitotic cells and cells with aberrant nuclear morphology showed increased cytoplasmic staining in DCIS and IDC. PKC alpha activity is altered in dividing or abnormal cells, but overall expression is reduced in IDC. This raises the possibility of an alteration in the subcellular localisation of PKC alpha which may relate to changes in desmosomal adhesive state.}, } @article {pmid15454194, year = {2004}, author = {Molland, JG and Donnellan, M and Janu, NC and Carmalt, HL and Kennedy, CW and Gillett, DJ}, title = {Infiltrating lobular carcinoma--a comparison of diagnosis, management and outcome with infiltrating duct carcinoma.}, journal = {Breast (Edinburgh, Scotland)}, volume = {13}, number = {5}, pages = {389-396}, doi = {10.1016/j.breast.2004.03.004}, pmid = {15454194}, issn = {0960-9776}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/surgery ; Breast Neoplasms, Male/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Carcinoma, Lobular/*diagnosis/surgery ; Female ; Humans ; Male ; Mastectomy/*methods ; Middle Aged ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {The treatment and outcomes for 182 patients with lobular carcinoma were compared with 1612 patients with infiltrating ductal carcinoma managed concurrently at The Strathfield Breast Centre. The lobular carcinomas were larger (P < 0.0001) but of lower grade (P < 0.0001). Diagnosis with mammography and FNA was less sensitive in ILC (mammography P = 0.0002, FNA P < 0.0001). Although similar numbers of patients underwent initial attempted conservation, patients with ILC were more likely to have positive margins at attempted breast conservation surgery and the final mastectomy rate was higher (58.2% ILC versus 47% IDC, P = 0.0041). Of the patients who had successful conservation, the local recurrence rates for ILC (3.9%) were equivalent to the patients with IDC (5.3%). There was no significant difference in overall survival (90% ILC, 87% IDC, median follow-up 3.6 years ILC, 4.3 years IDC) or disease free survival (87.9% ILC, 81.6% IDC). Although mastectomy is more likely to be necessary to obtain clear margins, breast conservation therapy is reasonable in patients with infiltrating lobular carcinoma where clear margins can be obtained.}, } @article {pmid15452174, year = {2004}, author = {Adams, SA and Smith, ME and Cowley, GP and Carr, LA}, title = {Reversal of glandular polarity in the lymphovascular compartment of breast cancer.}, journal = {Journal of clinical pathology}, volume = {57}, number = {10}, pages = {1114-1117}, pmid = {15452174}, issn = {0021-9746}, mesh = {Animals ; Antibodies, Monoclonal/analysis ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Laminin/analysis ; Lymphatic System/pathology ; Mice ; Platelet Endothelial Cell Adhesion Molecule-1/analysis ; }, abstract = {AIM: To investigate the polarity of breast invasive ductal carcinoma cells by comparing the polarity of the tumour located within lymphovascular spaces with that located in the extravascular compartment.

METHODS: An immunohistochemical study identifying the apical HMFG-1, basolateral AUA-1, and basal laminin polarity markers of 11 cases of invasive ductal carcinoma (grades 1 or 2) metastatic to lymph nodes, all of which contained areas of tumour within and outside of lymphovascular spaces.

RESULTS: Only one of 11 tumours had a focus of apparent reversed glandular polarity in the larger extravascular tumour compartment (with AUA-1 present internally and HMFG-1 expressed externally on tumour clumps), but six of the 11 tumours showed reversed glandular polarity (either with AUA-1, or HMFG-1, or both) within the very much smaller lymphovascular space tumour compartment. Laminin was not identified in association with lymphovascular tumour.

CONCLUSIONS: Reversed glandular polarity in invasive ductal breast carcinomas was identified and was significantly more frequent within vessels than outside of them. Reversal of tumour glandular polarity within lymphovascular spaces allows direct interaction between apical domain-type molecules-which are then aberrantly expressed on the external surface of tumour clumps-and lymphovascular endothelium. Such interactions may affect the establishment of metastatic disease.}, } @article {pmid15377846, year = {2004}, author = {Lawson, JS and Tran, DD and Ford, C and Rawlinson, WD}, title = {Elevated expression of the tumor suppressing protein p53 is associated with the presence of mouse mammary tumor-like env gene sequences (MMTV-like) in human breast cancer.}, journal = {Breast cancer research and treatment}, volume = {87}, number = {1}, pages = {13-17}, doi = {10.1023/B:BREA.0000041573.09142.00}, pmid = {15377846}, issn = {0167-6806}, mesh = {Animals ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*genetics/*virology ; Carcinoma, Ductal, Breast/*genetics/*virology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*virology ; *Gene Expression Profiling ; Genes, env/*genetics ; Humans ; Mammary Neoplasms, Animal/virology ; Mammary Tumor Virus, Mouse/*genetics/pathogenicity ; Mice ; Polymerase Chain Reaction ; Tumor Suppressor Protein p53/*biosynthesis ; }, abstract = {Mouse mammary tumor virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible laboratory inbred mice. The carcinogenic characteristics of this virus are enhanced by estrogen and other steroid hormones. MMTV-like envelope gene sequences, with 95% homology to MMTV have been identified in approximately 40% of breast cancers in US, Australian and Argentinian women. The presence of such sequences indicates the presence of a replication competent MMTV-like virus in human breast tumors. Whether an MMTV-like virus contributes to human breast cancer remains to be demonstrated. Non-statistically significant differences in p53 expression between MMTV-like positive and negative human breast cancers have previously been observed. As high p53 protein expression is associated with aggressive breast carcinogenesis we sought to determine if there were associations between the presence of MMTV-like gene sequences and elevated p53 expression in both invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS). We also investigated the expression of other biomarkers which are commonly associated with human breast cancer. These included estrogen receptor, progesterone receptor, Ki67, Cyclin D1, Bcl-2 and HER-2. Using polymerase chain reaction (PCR) analyses, MMTV-like envelope gene sequences were detected in 15 (75%) of 20 IDC specimens and 5 (23%) of 22 DCIS specimens. The average percentage of p53 positive cells in MMTV-like positive IDC specimens was 69% as compared to 44% in MMTV-like negative specimens (p for difference = 0.067). The average percentage of p53 positive cells in MMTV-like positive DCIS specimens was 93% as compared to 35% in MMTV-like negative specimens (numbers too few for statistical analysis). There was an increased intensity of p53 expression in IDC and DCIS specimens that were MMTV-like positive compared to those that were MMTV-like negative. There were no statistically significant differences in age, grade, and percentage of average positive cells for ERa, PR, Ki67, cyclin D1, Bcl-2, and HER-2, between MMTV-like positive and negative breast cancer specimens. Although these observations do not provide evidence of causality, they are consistent with a role for MMTV-like viruses in some human breast cancers.}, } @article {pmid15375712, year = {2004}, author = {Abe, H and Hanasawa, K and Naitoh, H and Endo, Y and Tani, T and Kushima, R}, title = {Invasive ductal carcinoma within a fibroadenoma of the breast.}, journal = {International journal of clinical oncology}, volume = {9}, number = {4}, pages = {334-338}, doi = {10.1007/s10147-004-0401-9}, pmid = {15375712}, issn = {1341-9625}, mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Fine-Needle ; Breast Neoplasms/etiology/*pathology/therapy ; Carcinoma, Ductal, Breast/etiology/*pathology/therapy ; Combined Modality Therapy ; Cyclophosphamide/therapeutic use ; Female ; Fibroadenoma/complications/*pathology/therapy ; Fluorouracil/therapeutic use ; Humans ; Lymphatic Metastasis ; Mastectomy/methods ; Methotrexate/therapeutic use ; Treatment Outcome ; }, abstract = {A rare case of invasive ductal carcinoma within a fibroadenoma of the breast in a 42-year-old woman is reported. The patient had a well-defined mass, measuring 6.0 x 5.0 cm, in the upper lateral quadrant of the left breast. Physical examination suggested fibroadenoma. Ultrasonography and mammography revealed some malignant findings. Needle biopsy demonstrated fibroadenoma. Frozen section revealed invasive ductal carcinoma, scirrhous type, arising in a fibroadenoma; muscle-preserving mastectomy was performed. Only 16 cases of carcinoma within a fibroadenoma of the breast have been reported in the literature in Japan. Carcinoma in a fibroadenoma should be treated on the basis of the therapeutic criteria for ordinary carcinoma.}, } @article {pmid15375528, year = {2004}, author = {Nishidate, T and Katagiri, T and Lin, ML and Mano, Y and Miki, Y and Kasumi, F and Yoshimoto, M and Tsunoda, T and Hirata, K and Nakamura, Y}, title = {Genome-wide gene-expression profiles of breast-cancer cells purified with laser microbeam microdissection: identification of genes associated with progression and metastasis.}, journal = {International journal of oncology}, volume = {25}, number = {4}, pages = {797-819}, pmid = {15375528}, issn = {1019-6439}, mesh = {Adult ; Aged ; Breast Neoplasms/*genetics/pathology ; Disease Progression ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lasers ; Lymphatic Metastasis ; Microdissection ; Middle Aged ; Multigene Family ; }, abstract = {Breast carcinoma is a complex disease characterized by accumulation of multiple genetic alterations, and the understanding of the molecular basis of mammary tumorigenesis is still incomplete. In this study we analyzed gene-expression profiles of 81 surgical specimens of 12 ductal carcinoma in situ (DCIS) and 69 invasive ductal carcinoma (IDC). After applying laser-microbeam micro-dissection to all samples we achieved 98-99% pure populations of breast cancer cells, and of normal breast epithelial cells used as controls. A cDNA-microarray analysis of 23,040 genes in these samples and a subsequent unsupervised hierarchical clustering distinguished two tumor groups, mainly in terms of estrogen-receptor (ER) status. We then undertook a supervised analysis and identified 325 genes that were commonly either up- or down-regulated in both pathologically discrete stages (DCIS and IDC), indicating that these genes might play important roles in malignant transformation of breast ductal cells. In addition, we searched invasion-associated gene candidates whose expression was altered in IDC, but not in DCIS, and identified 24 up-regulated genes and 41 down-regulated genes. Furthermore, we identified 34 genes that were expressed differently in tumors from patients with lymph node metastasis as opposed to no metastasis. On that basis we developed a scoring system that correlated well with the metastatic status. Tumors from all of the 37 test patients with lymph-node metastasis yielded positive scores by our definition, whereas 38 of the 40 tumors (95%) without lymph node metastasis had negative scores. Our data should provide useful information for identifying predictive markers for invasion or metastasis, and suggest potential target molecules for treatment of breast cancers.}, } @article {pmid15374801, year = {2004}, author = {Koike, A and Hoshimoto, M and Nagayama, O and Tajima, A and Kubozono, T and Oikawa, K and Uejima, T and Momose, T and Aizawa, T and Fu, LT and Itoh, H}, title = {Cerebral oxygenation during exercise and exercise recovery in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {94}, number = {6}, pages = {821-824}, doi = {10.1016/j.amjcard.2004.06.013}, pmid = {15374801}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/*physiopathology ; *Cerebrovascular Circulation ; Exercise/*physiology ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Oxygen/*blood ; Ventricular Dysfunction, Left/*physiopathology ; }, abstract = {We compared cerebral oxygenation during exercise and during exercise recovery between 22 healthy subjects and 35 patients with idiopathic dilated cardiomyopathy (IDC). Although cerebral oxyhemoglobin increased during exercise in most of the healthy subjects, oxyhemoglobin decreased during exercise in 15 of 35 patients with IDC. Cerebral oxygenation during exercise and exercise recovery was related to left ventricular function in the patients with IDC.}, } @article {pmid15368805, year = {2004}, author = {Stöllberger, C and Leitner, S and Kopsa, W and Finsterer, J}, title = {Left ventricular hypertrabeculation/noncompaction and neuromuscular disorders in idiopathic dilated cardiomyopathy.}, journal = {Acta cardiologica}, volume = {59}, number = {4}, pages = {425-430}, doi = {10.2143/AC.59.4.2005209}, pmid = {15368805}, issn = {0001-5385}, mesh = {Aged ; Austria ; Cardiomyopathy, Dilated/*diagnosis/*etiology/metabolism ; Coronary Angiography ; Echocardiography ; Electrocardiography ; Electromyography ; Female ; Follow-Up Studies ; Heart Ventricles/diagnostic imaging/pathology ; Humans ; Hypertrophy, Left Ventricular/*diagnosis/*etiology/metabolism ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myocardium/enzymology/pathology/ultrastructure ; Neuromuscular Diseases/*diagnosis/*etiology/metabolism ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Our aim was to assess 1) the association of idiopathic dilative cardiomyopathy (IDC) and left ventricular hypertrabeculation/noncompaction (LVHT), 2) the use of cardiac magnetic resonance imaging (CMRI) in IDC and 3) the association of IDC and neuromuscular disorders (NMD).

METHODS: Patients in whom coronary heart disease had been excluded by coronary angiography and whose left ventricular end diastolic diameter was > 59 mm and fractional shortening < 25% with no other causes of cardiac dysfunction, were invited to participate.

RESULTS: Among 25 patients, 18 refused CMRI (claustrophobia n = 13, inability to lie flat n = 5), thus 7 patients (2 female, 47-66 years) were included. LVHT was found in 5/7 cases. In 4/5 patients who were neurologically investigated, a NMD was found. In 2/7 cases echocardiography failed to visualise the ventricular apex.

CONCLUSIONS: Patients with IDC should be investigated neurologically. In IDC patients with poor echocardiographic quality CMRI should be applied.}, } @article {pmid15368253, year = {2004}, author = {Yoshida, M and Babensee, JE}, title = {Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells.}, journal = {Journal of biomedical materials research. Part A}, volume = {71}, number = {1}, pages = {45-54}, doi = {10.1002/jbm.a.30131}, pmid = {15368253}, issn = {1549-3296}, mesh = {Animals ; Antigens, CD/immunology ; Biocompatible Materials/*pharmacology ; Biomarkers ; Cell Culture Techniques/methods ; Cell Shape ; Cells, Cultured ; Dendritic Cells/cytology/*drug effects/immunology/physiology ; Glycolates/immunology/*pharmacology ; Humans ; Hypersensitivity, Delayed ; Lactic Acid ; Lymphocyte Culture Test, Mixed ; Materials Testing ; Mice ; Monocytes/cytology/*drug effects/immunology/physiology ; Phenotype ; Polyglycolic Acid ; Polylactic Acid-Polyglycolic Acid Copolymer ; }, abstract = {Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysaccharide (LPS) treatment for DC maturation or negative control of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhancement of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, biomaterial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a moderate delayed type hypersensitivity reaction in mice indicative of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation.}, } @article {pmid15363314, year = {2004}, author = {Zhang, JL and Zhang, HY and Wei, B and Lang, ZQ and Bu, H}, title = {[Role of cytokeratin expression in differential diagnosis of intraductal proliferative lesions of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {33}, number = {4}, pages = {316-319}, pmid = {15363314}, issn = {0529-5807}, mesh = {Breast/chemistry/*pathology ; Breast Neoplasms/chemistry/*diagnosis/pathology ; Carcinoma, Ductal, Breast/chemistry/diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*diagnosis ; Cell Line, Tumor ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Keratins/*analysis ; Precancerous Conditions/chemistry/*pathology ; }, abstract = {OBJECTIVE: To evaluate the expression of cytokeratins in intraductal proliferative lesions of breast, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma-in-situ (DCIS) and its role in differential diagnosis.

METHODS: Ninety two cases of paraffin-embedded lesional breast tissue, 30 cases of frozen samples, cell cultures of hyperplastic ductal cells and 2 invasive ductal carcinoma cell lines (T47D and MCF-7) were used for this study. Immunohistochemistry was performed using EnVision method for 34betaE12, CK8 and CK14.

RESULTS: The percentage of 34betaE12-positivity in paraffin-embedded samples of UDH, ADH, DCIS and invasive ductal carcinoma (IDC) was found to be 95.2%, 33.3%, 19.2% and 12.5% respectively. In frozen tissues, all UDH cases and 55% of IDC cases expressed 34betaE12. The primary UDH cell cultures and T47D cell line were also 34betaE12-positive, whereas MCF7 cell line showed negative staining. The expression rate of CK8 and CK14 in UDH was also different from that in ADH and DCIS.

CONCLUSIONS: 34betaE12 can be useful in differential diagnosis of intraductal proliferative lesions of the breast. However application of this cytokeratin stain in intraoperative frozen sections is relatively limited. The expression patterns of CK8 and CK14 are also helpful in the differential diagnosis of similar lesions.}, } @article {pmid15363312, year = {2004}, author = {Fan, Y and Lang, RG and Wang, Y and Sun, BC and Fu, L}, title = {[Relationship between expression of cell adhesion molecules and metastatic potential in invasive micropapillary carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {33}, number = {4}, pages = {308-311}, pmid = {15363312}, issn = {0529-5807}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/metabolism/secondary ; Carcinoma, Papillary/*metabolism/secondary ; Cell Membrane/*metabolism ; Cytoskeletal Proteins/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Trans-Activators/metabolism ; alpha Catenin ; beta Catenin ; }, abstract = {OBJECTIVE: To investigate the expression of cell adhesion molecules and Their significance in invasive micropapillary carcinoma (IMPC) of the breast.

METHODS: Immunohistochemical study for E-cadherin was performed on 64 cases of IMPC and 57 cases of invasive ductal carcinoma (IDC).

RESULTS: E-cadherin was mainly expressed on the cell membrane of tumor cells. The expression of E-cadherin in IMPC (85.9%, 55/64) was significantly higher than that in IDC (43.9%, 25/57). E-cadherin expressed in the intercellular contact surface of IMPC cells. In contrast, it was weakly positive/not expressed on the outer membranous surface of the tumor clusters in IMPC. The rate of lymph node metastasis in IMPC (85.9%, 55/64) was significantly higher than that in IDC (52.6%, 30/57), the rate of alpha-catenin and beta-catenin coexpression in IMPC (45.1%, 26/51) with lymph node metastasis and E-cadherin normal expression was also significantly higher than that in IDC (15.4%, 2/13).

CONCLUSION: Weak cell adhesion molecule expression on the outer surface of IMPC cell clusters, in contrast to strong cohesion in intercellular contact surface, may help to explain the high metastatic potential of this type of breast cancer.}, } @article {pmid15362227, year = {2004}, author = {Campbell, ID and Ginsberg, MH}, title = {The talin-tail interaction places integrin activation on FERM ground.}, journal = {Trends in biochemical sciences}, volume = {29}, number = {8}, pages = {429-435}, doi = {10.1016/j.tibs.2004.06.005}, pmid = {15362227}, issn = {0968-0004}, mesh = {Animals ; *Cell Adhesion ; *Cell Movement ; Cytoskeleton ; Extracellular Matrix ; Humans ; *Inflammation ; Integrin beta Chains/chemistry/*metabolism ; Ligands ; *Neovascularization, Physiologic ; Protein Binding ; Signal Transduction ; Talin/*metabolism ; }, abstract = {Integrins are essential receptors for the development and functioning of multicellular animals because they mediate cell migration and cell adhesion, and regulate cell proliferation and apoptosis. Cellular regulation of the affinity of integrins for ligands - so-called 'integrin activation' - is a central property of these receptors. Integrin activation controls cell adhesion, migration and extracellular matrix assembly, thereby contributing to processes such as angiogenesis, tumor cell metastasis, inflammation, the immune response and hemostasis. Recent studies indicate that a crucial, final step in integrin activation is the binding of talin, a cytoskeletal protein, to the cytoplasmic domain of the integrin beta subunit. These results provide a focus for unraveling the many biochemical pathways implicated in integrin activation and suggest a general structural model for the connections between integrins and diverse cellular signal transduction pathways.}, } @article {pmid15361217, year = {2004}, author = {Ohira, S and Itoh, K and Osada, K and Oka, K and Suzuki, A and Osada, R and Kobayashi, M and Konishi, I}, title = {Vulvar Paget's disease with underlying adenocarcinoma simulating breast carcinoma: case report and review of the literature.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {14}, number = {5}, pages = {1012-1017}, doi = {10.1111/j.1048-891X.2004.14544.x}, pmid = {15361217}, issn = {1048-891X}, mesh = {Adenocarcinoma/*diagnosis/*pathology/surgery ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Paget Disease, Extramammary/*diagnosis/*pathology/surgery ; Vulvar Neoplasms/*diagnosis/*pathology/surgery ; }, abstract = {We report a case of extramammary Paget's disease with underlying adenocarcinoma simulating breast carcinoma of the vulva. An 82-year-old woman was found to have a 5 x 3-cm bulky tumor located in the left labium major, infiltrating to the clitoris, left labium minor, and left lateral tissue of the vulva. Small biopsy of the vulva showed intraepidermal proliferation of Paget cells. The patient underwent wide local excision of the vulvar tumor and dissection of left inguinal lymph nodes. Histopathological examination of the resected specimens revealed that Paget cells were distributed singly or tended to form small nests in the epidermis, and that association of these cells with the underlying carcinoma invading to the subcutis could be seen. The underlying carcinoma was composed of squamoid solid nests with central necrotic debris, mimicking 'comedocarcinoma' of the breast. In other areas, the tumor cells were present in tubular formations and solid cords reminiscent of invasive ductal carcinoma of the breast. Immunohistochemically, the Paget cells and the underlying carcinoma cells were positive for carcinoembryonic antigen, epithelial membrane antigen, estrogen receptors, and glandular keratins except for CK 20. We speculate that our case is vulvar Paget's disease presenting as a manifestation of underlying breast carcinoma of the vulva, which might have arisen from either the ectopic breast tissue or anogenital mammary-like glands.}, } @article {pmid15358256, year = {2004}, author = {Llinás, M and DeRisi, JL}, title = {Pernicious plans revealed: Plasmodium falciparum genome wide expression analysis.}, journal = {Current opinion in microbiology}, volume = {7}, number = {4}, pages = {382-387}, doi = {10.1016/j.mib.2004.06.014}, pmid = {15358256}, issn = {1369-5274}, mesh = {Animals ; Erythrocytes/*parasitology ; Gene Expression Profiling/methods ; *Gene Expression Regulation ; *Genome, Protozoan ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*growth & development ; *Proteome ; Protozoan Proteins/genetics/*metabolism ; }, abstract = {The asexual intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum is responsible for the majority of the clinical manifestations of malaria in humans. Although malaria has been studied for over a century, the elucidation of the full genome sequence of P. falciparum has now allowed for in-depth studies of gene expression throughout the entire intraerythrocytic stage. As the mainstays of anti-malarial chemotherapy become increasingly ineffective, we need a deeper understanding of fundamental plasmodial bioregulatory mechanisms to successfully subvert them. Recent gene expression studies have begun to examine different aspects of the IDC and are providing key insights into the basic mechanisms of Plasmodium gene regulation and are helping to define gene functions. However, to date, no transcription factor has been fully characterized from Plasmodium and the definitive identification of cis-acting regulatory elements along with their corresponding trans-acting partners is still lacking. The characterization of the transcriptome of P. falciparum is the first major step towards the understanding of the genome wide regulation of gene expression in this parasite. IDC expression data for almost every gene in the P. falciparum genome can now be publicly queried at and. The results of these studies suggest promising leads for identifying novel targets for anti-malarial therapeutics and vaccines in addition to providing a solid foundation for the ongoing elucidation of plasmodial gene expression.}, } @article {pmid15356156, year = {2004}, author = {Skorokhod, OA and Alessio, M and Mordmüller, B and Arese, P and Schwarzer, E}, title = {Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptor-gamma-mediated effect.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {6}, pages = {4066-4074}, doi = {10.4049/jimmunol.173.6.4066}, pmid = {15356156}, issn = {0022-1767}, mesh = {Aldehydes/metabolism/pharmacology ; Animals ; Antigens, CD ; Antigens, CD1/biosynthesis ; Antigens, Surface/biosynthesis ; Apoptosis/immunology ; Biotransformation ; Cell Differentiation/immunology ; Dendritic Cells/*immunology/metabolism/parasitology/pathology ; Growth Inhibitors/metabolism/pharmacology/*physiology ; Hemeproteins/metabolism/*physiology ; Humans ; Hydroxyeicosatetraenoic Acids/metabolism/physiology ; Immunoglobulins/biosynthesis/genetics ; Immunosuppressive Agents/metabolism/*pharmacology ; Leukocyte Count ; Ligands ; Membrane Glycoproteins/antagonists & inhibitors/biosynthesis/genetics ; Monocytes/*immunology/metabolism/parasitology/pathology ; NF-kappa B/metabolism ; Peroxisomes/immunology/metabolism/parasitology/pathology ; Phagocytosis/immunology ; Pigments, Biological/metabolism/*physiology ; Plasmodium falciparum/*immunology ; RNA, Messenger/antagonists & inhibitors/biosynthesis ; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism/*physiology ; Transcription Factors/biosynthesis/genetics/metabolism/*physiology ; Up-Regulation/immunology ; }, abstract = {Acute and chronic Plasmodium falciparum malaria are accompanied by severe immunodepression possibly related to subversion of dendritic cells (DC) functionality. Phagocytosed hemozoin (malarial pigment) was shown to inhibit monocyte functions related to immunity. Hemozoin-loaded monocytes, frequently found in circulation and adherent to endothelia in malaria, may interfere with DC development and play a role in immunodepression. Hemozoin-loaded and unloaded human monocytes were differentiated in vitro to immature DC (iDC) by treatment with GM-CSF and IL-4, and to mature DC (mDC) by LPS challenge. In a second setting, hemozoin was fed to iDC further cultured to give mDC. In both settings, cells ingested large amounts of hemozoin undegraded during DC maturation. Hemozoin-fed monocytes did not apoptose but their differentiation and maturation to DC was severely impaired as shown by blunted expression of MHC class II and costimulatory molecules CD83, CD80, CD54, CD40, CD1a, and lower levels of CD83-specific mRNA in hemozoin-loaded iDC and mDC compared with unfed or latex-loaded DC. Further studies indicated activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in hemozoin-loaded iDC and mDC, associated with increased expression of PPAR-gamma mRNA, without apparent involvement of NF-kappaB. Moreover, expression of PPAR-gamma was induced and up-regulation of CD83 was inhibited by supplementing iDC and mDC with plausible concentrations of 15(S)-hydroxyeicosatetraenoic acid, a PPAR-gamma ligand abundantly produced by hemozoin via heme-catalyzed lipoperoxidation.}, } @article {pmid15354746, year = {2004}, author = {Vassallo, J and Pinto, GA and Alvarenga, JM and Zeferino, LC and Chagas, CA and Metze, K}, title = {Comparison of immunoexpression of 2 antibodies for estrogen receptors (1D5 and 6F11) in breast carcinomas using different antigen retrieval and detection methods.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {12}, number = {2}, pages = {177-182}, doi = {10.1097/00129039-200406000-00014}, pmid = {15354746}, issn = {1541-2016}, mesh = {*Antibodies, Monoclonal ; Antigen-Antibody Reactions ; Antigens, Neoplasm/*analysis/immunology ; Carcinoma, Ductal, Breast/*diagnosis ; Female ; Humans ; Immunohistochemistry/methods ; Receptors, Estrogen/*analysis/immunology ; }, abstract = {The importance of in situ immunodetection of hormone receptors for therapy planning and prognostic evaluation in patients with breast carcinoma is well established. Sensitive detection methods are of utmost importance, especially in poorly fixed tissues, which are not uncommon in routine pathologic practice. The purpose of the present study is to compare immunoexpression of estrogen receptors in 20 cases of invasive ductal carcinoma using two antibodies, 1D5 and 6F11, and to verify the effect of different antigen retrieval solutions and detection systems. Immunoperoxidase was performed on paraffin sections using 1D5 and 6F11 as primary antibodies. Heat-induced antigen retrieval was performed using citrate buffer (pH 6.0) or Tris-EDTA buffer (pH 8.9). Detection was achieved using the following systems: EnVision, EnVision Plus, and labeled streptavidin-biotin peroxidase complex. Reaction was semiquantified from 0 to 4. There were no differences between the two markers, 1D5 and 6F11, except when 6F11 was used with EnVision and citrate buffer, in which case weaker reactivity was observed. Only in this combination (6F11/EnVision) was EDTA buffer significantly better than citrate. Labeled streptavidin-biotin peroxidase complex presented the best results, followed by EnVision Plus.}, } @article {pmid15343133, year = {2004}, author = {Caruso, G and Ienzi, R and Piovana, G and Ricotta, V and Cirino, A and Salvaggio, G and Lagalla, R}, title = {High-frequency ultrasound in the study of male breast palpable masses.}, journal = {La Radiologia medica}, volume = {108}, number = {3}, pages = {185-193}, pmid = {15343133}, issn = {0033-8362}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Diseases/*diagnostic imaging/surgery ; Breast Neoplasms, Male/diagnostic imaging ; Carcinoma/diagnostic imaging ; Child ; Fibroma ; Follow-Up Studies ; Gynecomastia/diagnostic imaging ; Humans ; Liposarcoma/diagnostic imaging ; Male ; Middle Aged ; Radiography ; *Ultrasonography, Doppler, Color ; }, abstract = {PURPOSE: To evaluate the role of high frequency colour-Doppler ultrasound in the study of diffuse or local breast nodules in males, and compare these results with those of mammography.

MATERIALS AND METHODS: We studied 105 men aged between 12 and 82 years (mean age 42.3 years) with a palpable breast mass with or without pain. All patients underwent clinical and ultrasound examination. Seventy-eight also underwent mammography, whereas 27 did not because of young age (under 25 years) (n=10), no clinical or sonographic suspicion of a malignant mass (n=16), and ulcerated neoplastic lesion (n=1). The final diagnosis derived from surgery in six patients and from three-year follow-up for 99 patients.

RESULTS: Eighty-nine patients had gynecomastia (85%), nine had adipomastia (8%), one had fibrolipoma (1%), five had carcinoma (5%) (invasive ductal carcinoma in four and bifocal ductal carcinoma and lobular carcinoma in one patient) and one had liposarcoma (1%). The clinical examination detected a bilateral (n=66) or unilateral (n=39) breast mass. Ultrasonography provided the correct diagnosis of diffuse nodular pathology in all cases and orientated diagnosis towards malignancy (6 cases) or benignity (1 case) of the lesions. No additional information was obtained from mammography, as compared to high-frequency ultrasonography. The integration of colour-Doppler in the examination was of little use as it demonstrated extensive vascularisation of most (5 cases) of the malignant lesions.

CONCLUSIONS: Our results indicate that ultrasound allows the detection and characterization of palpable breast masses as well as correct local staging of neoplasms by identifying the degree of infiltration of the surrounding tissues.}, } @article {pmid15342290, year = {2004}, author = {Fujioka, S and Kitaura, Y and Deguchi, H and Shimizu, A and Isomura, T and Suma, H and Sabbah, HN}, title = {Evidence of viral infection in the myocardium of American and Japanese patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {94}, number = {5}, pages = {602-605}, doi = {10.1016/j.amjcard.2004.05.023}, pmid = {15342290}, issn = {0002-9149}, mesh = {Adult ; Cardiomyopathy, Dilated/complications/*ethnology/*virology ; Coxsackievirus Infections ; Enterovirus ; Female ; Heart/*virology ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Myocarditis/*complications/*ethnology/virology ; United States/epidemiology ; Virus Diseases/complications ; }, abstract = {Enteroviruses have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Recently, the association of adenovirus or parvovirus with IDC has been reported. Viral infection in the myocardium of American and Japanese patients with end-stage IDC was evaluated. Myocardial specimens from 30 American patients with IDC and 47 Japanese patients with IDC were analyzed for the presence of cardiotropic viruses. The strand-specific detection of enteroviral ribonucleic acid (RNA) was performed to determine viral activity in hearts with IDC. Established reverse transcription-polymerase chain reaction (PCR) or PCR techniques were used to detect genomic sequences of influenza viruses, mumps virus, adenovirus, parvovirus, herpes simplex viruses, varicella-zoster virus, and Epstein-Barr virus. Enteroviral RNA was detected in 7 of the 30 American patients (23%) and in 15 of the 47 Japanese patients (32%). Minus-strand enteroviral RNA, an indicator of active enteroviral RNA replication, was demonstrated in 5 of 7 plus-strand-positive American patients (71%) and in 12 of 15 plus-strand-positive Japanese patients (80%). Sequence analysis revealed that the viruses detected were Coxsackie B viruses. No genomic sequences of other viruses were detected in the myocardium of either American or Japanese patients with IDC. Therefore, active group B Coxsackie virus RNA replication in the myocardium was demonstrated in a significant proportion of American and Japanese patients with end-stage IDC. There was no evidence of persistent infection by other viruses in hearts with IDC. Specific therapy should be designed for Coxsackie virus positive patients with IDC.}, } @article {pmid15338348, year = {2004}, author = {Kijima, Y and Yoshinaka, H and Owaki, T and Nozaki, T and Hamada, T and Yasumoto, Y and Aikou, T}, title = {Breast cancer with nephrotic syndrome: report of two cases.}, journal = {Surgery today}, volume = {34}, number = {9}, pages = {755-759}, doi = {10.1007/s00595-004-2811-8}, pmid = {15338348}, issn = {0941-1291}, mesh = {Breast Neoplasms/*complications/diagnosis/surgery ; Carcinoma, Ductal, Breast/*complications/diagnosis/surgery ; Female ; Glomerulonephritis, Membranous/*etiology ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Nephrotic Syndrome/*etiology ; Treatment Outcome ; }, abstract = {We report two cases of women found to have breast cancers within a few months of being diagnosed with nephrotic syndrome. Case 1 was a 53-year-old Japanese woman in whom breast cancer was diagnosed 14 months after the onset of nephrotic syndrome. The histological diagnosis was invasive ductal carcinoma with no lymph node metastasis. We performed a modified radical mastectomy, after which the proteinuria and hypoproteinemia resolved almost completely, and the patient has been disease-free for 5 years since. Case 2 was a 61-year-old Japanese woman in whom breast cancer was diagnosed 2 months after the onset of membranous nephropathy. We performed a modified radical mastectomy and the histological diagnosis was invasive ductal carcinoma with marked lymphatic vessel permeation and involvement of five axillary lymph nodes. Proteinuria and hypoproteinemia did not resolve postoperatively and there is a high possibility of remnant or recurrent cancer. To our knowledge, there are only four other reported cases of paraneoplastic membranous nephropathy complicating breast cancer. However, we speculate that the postoperative resolution of nephrotic syndrome might be a measure of cancer control.}, } @article {pmid15334643, year = {2004}, author = {Weizman, DA and Leong, WL}, title = {Anti-Ri antibody opsoclonus-myoclonus syndrome and breast cancer: a case report and a review of the literature.}, journal = {Journal of surgical oncology}, volume = {87}, number = {3}, pages = {143-145}, doi = {10.1002/jso.20103}, pmid = {15334643}, issn = {0022-4790}, mesh = {Aged ; Antigens, Neoplasm/*immunology ; Autoantibodies/analysis ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Nerve Tissue Proteins/*immunology ; Neuro-Oncological Ventral Antigen ; Paraneoplastic Syndromes, Nervous System/complications/*immunology ; Purkinje Cells/immunology ; RNA-Binding Proteins/*immunology ; }, abstract = {Opsoclonus-myoclonus is a rare neurological paraneoplastic syndrome associated with breast cancer and the presence of anti-Ri antibody. We presented a case of a 79-year-old woman with this syndrome and a small invasive ductal carcinoma [pT1aN0(sn)M0], whose symptoms improved 3 months following her simple mastectomy without any adjuvant therapy. Based on the 15 previously reported cases in the literature, there is no uniform treatment option available, and the response to such treatments is mixed.}, } @article {pmid15331393, year = {2005}, author = {Radstake, TR and van der Voort, R and ten Brummelhuis, M and de Waal Malefijt, M and Looman, M and Figdor, CG and van den Berg, WB and Barrera, P and Adema, GJ}, title = {Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with rheumatoid arthritis, and regulation by Fc gamma receptors.}, journal = {Annals of the rheumatic diseases}, volume = {64}, number = {3}, pages = {359-367}, pmid = {15331393}, issn = {0003-4967}, mesh = {Arthritis, Rheumatoid/*blood ; Cells, Cultured ; Chemokine CCL17 ; Chemokine CCL19 ; Chemokines, CC/biosynthesis/*blood/genetics ; Dendritic Cells/*metabolism ; Gene Expression Regulation ; Humans ; Monocytes/metabolism ; Polymerase Chain Reaction/methods ; RNA, Messenger/genetics ; Receptors, IgG/*physiology ; Severity of Illness Index ; Synovial Membrane/metabolism ; }, abstract = {BACKGROUND: Dendritic cells (DC) have a role in the regulation of immunity and tolerance, attracting inflammatory cells by the production of various chemokines (CK). Fc gamma receptors (Fc gamma R) may be involved in regulation of the DC function.

OBJECTIVE: To assess the expression of CK by immature (iDC) and mature DC (mDC) and its regulation by Fc gamma R in patients with RA and healthy donors (HC).

METHODS: Expression of CK by DC from patients with RA and from HC was determined by real time quantitative PCR and ELISA. DC were derived from monocytes following standardised protocols. To study the potential regulation by Fc gamma R, iDC were stimulated with immune complexes (IC) during lipopolysaccharide (LPS) induced maturation. The presence of CK was studied in synovial tissue from patients with RA, osteoarthritis, and healthy subjects by RT-PCR and immunohistochemistry.

RESULTS: iDC from patients with RA had markedly increased mRNA levels of the CK CCL18 and CXCL8. Upon maturation with LPS, expression of CCL18, CCL19, CXCL8, CCL3, and CCL17 increased dramatically, reaching significantly higher levels in patients with RA. Monocytes failed to express these CK, except for CXCL8 and CCL3. IC-mediated triggering of the Fc gamma R on DC from patients with highly active RA down regulated all CK, whereas the reverse was seen when DC from patients with low disease activity and healthy donors were stimulated. CCL18 was significantly increased in RA synovial tissue.

CONCLUSION: Increased CK expression by DC was found in patients with RA. This expression is partly regulated by Fc gamma R triggering and results in an inhibitory DC subtype in RA upon Fc gamma R-mediated triggering.}, } @article {pmid15330252, year = {2004}, author = {Castriconi, R and Della Chiesa, M and Moretta, A}, title = {Shaping of adaptive immunity by innate interactions.}, journal = {Comptes rendus biologies}, volume = {327}, number = {6}, pages = {533-537}, doi = {10.1016/j.crvi.2003.12.001}, pmid = {15330252}, issn = {1631-0691}, mesh = {Animals ; Cell Communication/immunology ; Dendritic Cells/*immunology ; *Immunity, Innate ; Killer Cells, Natural/*immunology ; Lymphocyte Activation ; Monocytes/immunology ; }, abstract = {In inflamed tissues, the reciprocal interaction between Natural Killer (NK) cells and Dendritic Cells (DC) results in a potent activating cross talk that leads to DC maturation and NK cell activation with acquisition of NK-mediated cytotoxicity against immature DC (iDC). We focused our studies on NK-mediated killing of monocyte-derived iDC and we provided evidence that NK cells that express CD94/NKG2A but not killer Ig-like receptors (KIR) are able to kill autologous iDC. Indeed HLA-E (i.e. the cellular ligand of CD94/NKG2A) is sharply reduced in iDC, whereas it is partially recovered in mDC. The latter are lysed only by a small fraction of NK clones characterized by low levels of CD94/NKG2A expression. Another NK receptor, whose surface density is crucial for the ability to kill iDC, is represented by NKp30, a member of the NCR (Natural Cytotoxicity Receptor) family. We showed that transforming growth factor beta1 (TGFbeta1) treatment results in specific downregulation of NKp30 expression. This effect profoundly inhibits the NK-mediated killing of DC suggesting a possible mechanism by which TGFbeta1-producing DC may acquire resistance to the NK-mediated attack.}, } @article {pmid15329866, year = {2004}, author = {Perret, D and Gentili, A and Marchese, S and Sergi, M and Caporossi, L}, title = {Determination of free fatty acids in chocolate by liquid chromatography with tandem mass spectrometry.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {18}, number = {17}, pages = {1989-1994}, doi = {10.1002/rcm.1582}, pmid = {15329866}, issn = {0951-4198}, mesh = {Cacao/*chemistry ; *Candy ; Chromatography, High Pressure Liquid/*methods ; Fatty Acids, Nonesterified/*analysis/classification ; Spectrometry, Mass, Electrospray Ionization/*methods ; }, abstract = {This paper describes a rapid extraction method, based on a matrix solid-phase dispersion technique using diatomaceous earth as solid support and 50:50 (v/v) chloroform/methanol as extracting solvent, that can determine 11 free fatty acids in chocolate. The extraction procedure is followed by reversed-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) using a normal-bore (4.6 mm i.d.) C-18 column and an electrospray interface operating in the negative ion mode. The tandem mass spectra of selected compounds show that charge-remote fragmentation (CRF) mechanisms are occurring; the intensities of the CRF reactions increase with the carbon number and degree of unsaturation of the fatty acids. Average recoveries, evaluated by the standard addition method, vary between 79-103%, and the estimated quantification limits are less than 153 ng/g. The proposed method has been used to analyse nine chocolate samples from various price ranges, bought from supermarkets.}, } @article {pmid15325944, year = {2004}, author = {Sade, LE and Kanzaki, H and Severyn, D and Dohi, K and Gorcsan, J}, title = {Quantification of radial mechanical dyssynchrony in patients with left bundle branch block and idiopathic dilated cardiomyopathy without conduction delay by tissue displacement imaging.}, journal = {The American journal of cardiology}, volume = {94}, number = {4}, pages = {514-518}, doi = {10.1016/j.amjcard.2004.04.071}, pmid = {15325944}, issn = {0002-9149}, support = {K24 HL 04503-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bundle-Branch Block/*diagnostic imaging/physiopathology/therapy ; Cardiomyopathy, Dilated/*diagnostic imaging/physiopathology/therapy ; Coronary Disease/diagnostic imaging/physiopathology/therapy ; *Echocardiography ; *Echocardiography, Doppler, Color ; *Electrocardiography ; Female ; Heart Failure/*diagnostic imaging/physiopathology/therapy ; Heart Septum/diagnostic imaging/physiopathology ; Humans ; *Image Processing, Computer-Assisted ; Male ; Middle Aged ; Myocardial Contraction/*physiology ; Reference Values ; Ventricular Dysfunction, Left/*diagnostic imaging/physiopathology/therapy ; Ventricular Function, Left/physiology ; }, abstract = {Cardiac resynchronization therapy has made assessment of cardiac dyssynchrony clinically important. To test the hypothesis that echocardiographic displacement imaging can quantify dyssynchrony, 22 patients with left bundle branch block (LBBB), 14 with idiopathic dilated cardiomyopathy (IDC) without electrical conduction delay, and 22 normal controls were studied using radial angle-corrected displacement imaging. Control subjects had coordinated wall movement, whereas patients with LBBB had dyssynchrony characterized by early inward anteroseptal movement and markedly delayed posterior, lateral, or inferior regions (157 +/- 99 ms; p <0.001 vs normal). An interesting subset of patients with IDC without conduction delay (36%) had dyssynchrony with anteroseptal to posterior wall delays of 169 +/- 56 ms (p <0.001 vs normal), similar to patients with LBBB.}, } @article {pmid15325673, year = {2004}, author = {Aryal, KR and Lengyel, AJ and Purser, N and Harrison, N and Aluwihare, N and Isgar, B}, title = {Nipple core biopsy for the deformed or scaling nipple.}, journal = {Breast (Edinburgh, Scotland)}, volume = {13}, number = {4}, pages = {350-352}, doi = {10.1016/j.breast.2003.12.007}, pmid = {15325673}, issn = {0960-9776}, mesh = {Aged ; Biopsy, Needle/methods ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/*diagnosis ; Eczema/*diagnosis ; Female ; Humans ; Nipples/*pathology ; Paget's Disease, Mammary/*diagnosis ; Receptors, Estrogen/analysis ; }, abstract = {The key to diagnosis for deformed or scaling nipple is cytology or histology. While scrape cytology and punch biopsy do not provide underlying breast tissue for histology wedge excision requires more time and resource. We present the technique of nipple core biopsy (NCB) in 40 patients with deformed or scaling nipple done as a part of triple assessment yielding both skin and breast tissue for histological examination. Histological diagnosis confirmed eczema in 24, Paget's disease of nipple in 9 and chronic inflammation in 2. Among 5 remaining patients with normal skin histology, underlying breast invasive ductal carcinoma was seen in 3, ductal carcinoma in situ (DCIS) in 1 and adenoma in 1. NCB identified 5(55%) significant breast pathologies in Paget's disease and detected a further 2 invasive cancers in the absence of a palpable mass. The technique also provides additional information in the form of oestrogen receptor, which can have direct impact on patient management.}, } @article {pmid15322200, year = {2004}, author = {Giese, A and Stuhlsatz, S and Däubener, W and MacKenzie, CR}, title = {Inhibition of the growth of Toxoplasma gondii in immature human dendritic cells is dependent on the expression of TNF-alpha receptor 2.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {5}, pages = {3366-3374}, doi = {10.4049/jimmunol.173.5.3366}, pmid = {15322200}, issn = {0022-1767}, mesh = {Animals ; Cell Differentiation/*immunology ; Dendritic Cells/*immunology/microbiology ; Humans ; Receptors, Tumor Necrosis Factor/antagonists & inhibitors/genetics/immunology/*metabolism ; Toxoplasma/growth & development/*immunology ; Toxoplasmosis/*immunology ; Tumor Necrosis Factor-alpha/immunology/metabolism ; }, abstract = {An effective immunity to Toxoplasma gondii in humans is dependent on the cellular immune response. Toxoplasma can infect and replicate in almost all nucleated cells, and the most important cytokine regulating the growth in humans is IFN-gamma; however, the role of TNF-alpha has to date been largely described to be synergistic. We show that, compared with mature human dendritic cells (mDC), immature human DC (iDC) demonstrate a reduced parasite proliferation when infected with Toxoplasma. This toxoplasmostasis was only present in iDC after 11 days of culture and was not present in DC that had been matured ex vivo using a cytokine mixture (mDC). Spontaneous toxoplasmostatic activity has previously only been described in fresh human monocytes, and the mechanism involved is as yet unclear. We show that, in comparison with an absence of expression in mDC, TNF-R2 is expressed in both iDC and monocytes infected with Toxoplasma, and furthermore, that blocking the TNF-R2 with Abs abrogates the toxoplasmostasis in the iDC. These findings demonstrate a functional role for TNF-R2 in the newly described spontaneous toxoplasmostasis of iDC.}, } @article {pmid15318940, year = {2004}, author = {Madrid, MA and Lo, RW}, title = {Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {5}, pages = {R593-600}, pmid = {15318940}, issn = {1465-542X}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization/*methods ; Nucleic Acid Amplification Techniques ; Receptor, ErbB-2/metabolism ; }, abstract = {BACKGROUND: Chromogenic in situ hybridization (CISH) is emerging as a practical, cost-effective, and valid alternative to fluorescent in situ hybridization in testing for gene alteration, especially in centers primarily working with immunohistochemistry (IHC).

METHODS: We assessed Her-2/neu alteration using CISH on formalin-fixed paraffin-embedded primary invasive ductal carcinoma tumors in which IHC (CB11 antibody) had previously been performed, and we compared the results with IHC. The 160 selected cases were equally stratified randomly into the four IHC categories (scores of 0, 1+, 2+, and 3+). We also compared age at diagnosis and tumor histologic grade with IHC and CISH Her-2/neu.

RESULTS: We were able to perform and evaluate CISH successfully on all cases. The agreement between 3+ IHC and CISH-amplified cases as well as between all IHC and CISH Her-2/neu negative cases was 100%, and the concordance on all positive cases was 72.50%, with an overall agreement of 86.25%. All the discordant cases had 2+ IHC scores. Although we noted Her-2/neu positivity more in premenopausal women, the age at diagnosis was not significantly associated with IHC or CISH results. Similarly, although the small group of well-differentiated tumors was apparently Her-2/neu negative in both tests, no significant association was noted between any tumor histologic grade and either IHC or CISH results.

CONCLUSIONS: CISH is easily integrated into routine testing in our laboratory. It is a necessary adjunct in determining the subset of non-amplified IHC-positive invasive tumors that will not benefit from trastuzumab therapy. Those cases with 2+ IHC results will be triaged and subjected to CISH. Her-2/neu testing should be done on all breast cancer cases regardless of age at presentation and tumor histologic grade.}, } @article {pmid15318932, year = {2004}, author = {Abba, MC and Drake, JA and Hawkins, KA and Hu, Y and Sun, H and Notcovich, C and Gaddis, S and Sahin, A and Baggerly, K and Aldaz, CM}, title = {Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {5}, pages = {R499-513}, pmid = {15318932}, issn = {1465-542X}, support = {U19 CA084978/CA/NCI NIH HHS/United States ; 1U19 CA84978/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Cycle ; Cell Division ; Extracellular Matrix ; Gene Expression ; *Gene Expression Profiling ; Gene Library ; Humans ; NF-kappa B ; Neoplasm Invasiveness/genetics ; Neoplasm Metastasis/genetics ; Tumor Necrosis Factor-alpha ; }, abstract = {INTRODUCTION: Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution.

METHODS: In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed.

RESULTS: We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01).

CONCLUSION: A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions with fully invasive lesions, a much more heterogeneous group, clearly identified as the most importantly deregulated group of transcripts those encoding for various families of proteins in charge of extracellular matrix remodeling, invasion and cell motility functions.}, } @article {pmid15312346, year = {2004}, author = {Zhang, XM and Zhang, ZW and Wu, H}, title = {[Correlation between uptake of 99Tcm-MIBI and expression of multidrug resistant protein in breast cancer].}, journal = {Zhonghua zhong liu za zhi [Chinese journal of oncology]}, volume = {26}, number = {6}, pages = {353-355}, pmid = {15312346}, issn = {0253-3766}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism ; Adolescent ; Adult ; Aged ; Breast Neoplasms/diagnostic imaging/*metabolism ; Carcinoma, Ductal, Breast/diagnostic imaging/*metabolism ; Female ; Humans ; Middle Aged ; Multidrug Resistance-Associated Proteins/*metabolism ; Radiopharmaceuticals/pharmacokinetics ; Technetium Tc 99m Sestamibi/*pharmacokinetics ; Tomography, Emission-Computed ; }, abstract = {OBJECTIVE: To assess the correlation between uptake of (99)Tc(m)-MIBI and expression level of multidrug resistant protein in breast cancer.

METHODS: Thirty pathologically confirmed patients with primary invasive ductal carcinoma were examined by (99)Tc(m)-MIBI scintigraphy at 15 min and 90 min after injecting the tracer. The uptake of (99)Tc(m)-MIBI at the region of interest (ROI) was evaluated as tumor to normal background (T/N) ratio. Retention index (RI) was calculated from the early uptake ratio (EUR) and updelayed take ratio (DUR). The expression of P-glycoprotein (P-gp) and multidrug resistant-associated protein (MRP) was detected by immunohistochemistry and the results were expressed as optical density (A). The data were analyzed by t test, Pearson correlation and partial correlation analysis.

RESULTS: The expression of P-gp and MRP in tumor tissue was 0.1183 +/- 0.0700 and 0.1195 +/- 0.0522, respectively. In group with RI < 0. the expression of P-gp and MRP was 0.2181 +/- 0.0384 and 0.1718 +/- 0.0479, respectively. In group with RI >/= 0, the expression of P-gp and MRP was 0.1057 +/- 0.0217 and 0.0967 +/- 0.0362, respectively. There were significant differences between the two groups (t = 6.61, P = 0.0001; t = 5.01, P = 0.002). There was positive correlation between P-gp and RI (r = -0.919, P = 0.001), DUR (r = -0.675, P = 0.001), MRP(r = 0.549, P = 0.001), respectively, but no correlation between P-gp and EUR (r = -0.097, P = 0.610). There was positive correlation between MRP and RI (r = -0.547, P = 0.002), but no correlation between MRP and EUR (r = 0.292, P = 0.117) or DUR (r = -0.173, P = 0.361). Partial correlation analysis showed that there was high positive correlation between P-gp and RI (r = -0.8847, P = 0.001), but no significant correlation between MRP and RI (r = -0.1296, P = 0.512).

CONCLUSION: The study suggests that increased level of P-gp expression may contribute to a low accumulation of (99)Tc(m)-MIBI in breast cancer, but no correlation with the expression level of MRP. Thus (99)Tc(m)-MIBI scintigraphy may predict the MDR development associated with P-gp expression in breast carcinoma.}, } @article {pmid15307010, year = {2004}, author = {DeJesus, E and McCarty, D and Farthing, CF and Shortino, DD and Grinsztejn, B and Thomas, DA and Schrader, SR and Castillo, SA and Sension, MG and Gough, K and Madison, SJ and , }, title = {Once-daily versus twice-daily lamivudine, in combination with zidovudine and efavirenz, for the treatment of antiretroviral-naive adults with HIV infection: a randomized equivalence trial.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {39}, number = {3}, pages = {411-418}, doi = {10.1086/422143}, pmid = {15307010}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; Aged ; Alkynes ; Anti-HIV Agents/administration & dosage ; Antiretroviral Therapy, Highly Active/*methods ; Benzoxazines ; CD4 Lymphocyte Count ; Cyclopropanes ; Disease Progression ; Double-Blind Method ; Drug Administration Schedule ; Drug Resistance, Viral ; Female ; HIV Infections/*drug therapy/virology ; HIV-1/drug effects/isolation & purification ; Humans ; Lamivudine/*administration & dosage/adverse effects ; Male ; Middle Aged ; Oxazines/administration & dosage ; RNA, Viral/blood ; Reverse Transcriptase Inhibitors/*administration & dosage/adverse effects ; Viral Load ; Zidovudine/administration & dosage ; }, abstract = {A randomized, double-blind, double-dummy controlled, multicenter trial was conducted that involved 554 antiretroviral-naive human immunodeficiency virus-infected adults (plasma HIV type 1 [HIV-1] RNA level, >or=400 copies/mL; CD4(+) cell count, >100 cells/mm(3)) and compared a 300-mg once-daily (q.d.) regimen of lamivudine (3TC) versus a 150-mg twice-daily (b.i.d.) regimen of 3TC, combined with zidovudine (300 mg b.i.d.) and efavirenz (600 mg q.d.), during a 48-week period. Treatments were considered equivalent if the 95% confidence interval (CI) for the difference in proportions of patients achieving an HIV-1 RNA level of <400 copies/mL was within the bound of -12% to 12%. At week 48 of the study, an intent-to-treat analysis in which patients with missing data were considered to have experienced treatment failure showed that the 3TC q.d. and 3TC b.i.d. regimens were equivalent (HIV-1 RNA level <400 copies/mL, 178 [64%] of 278 vs. 174 [63%] of 276; treatment difference, 1% [95% CI, -7.1% to 8.9%]; HIV-1 RNA level <50 copies/mL, 165 [59%] of 278 vs. 168 [61%] of 276; treatment difference, 1.7% [95% CI, -9.7% to 6.6%]). Median increase above baseline in CD4(+) cell count was similar (q.d. group, +144 cells/mm(3); b.i.d. group, +146 cells/mm(3)), and the incidences of adverse events, disease progression, and HIV-associated conditions were comparable.}, } @article {pmid15295005, year = {2004}, author = {Cignetti, A and Vallario, A and Roato, I and Circosta, P and Allione, B and Casorzo, L and Ghia, P and Caligaris-Cappio, F}, title = {Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that efficiently stimulate T cell responses.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {173}, number = {4}, pages = {2855-2865}, doi = {10.4049/jimmunol.173.4.2855}, pmid = {15295005}, issn = {0022-1767}, mesh = {CD40 Ligand/pharmacology ; Cell Differentiation/drug effects/*immunology ; Cell Movement/immunology ; Cells, Cultured ; Cytokines/biosynthesis/immunology ; Dendritic Cells/cytology/drug effects/*immunology ; Female ; Flow Cytometry ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute/*immunology ; Lipopolysaccharide Receptors/immunology ; Lymphocyte Activation/drug effects/*immunology ; Male ; Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/*immunology ; }, abstract = {Primary acute myeloid leukemia cells can be induced to differentiate into dendritic cells (DC). In the presence of GM-CSF, TNF-alpha, and/or IL-4, leukemia-derived DC are obtained that display features of immature DC (i-DC). The aim of this study was to determine whether i-DC of leukemic origin could be further differentiated into mature DC (m-DC) and to evaluate the possibility that leukemic m-DC could be effective in vivo as a tumor vaccine. Using CD40L as maturating agent, we show that leukemic i-DC can differentiate into cells that fulfill the phenotypic criteria of m-DC and, compared with normal counterparts, are functionally competent in vitro in terms of: 1) production of cytokines that support T cell activation and proliferation and drive Th1 polarization; 2) generation of autologous CD8(+) CTLs and CD4(+) T cells that are MHC-restricted and leukemia-specific; 3) migration from tissues to lymph nodes; 4) amplification of Ag presentation by monocyte attraction; 5) attraction of naive/resting and activated T cells. Irradiation of leukemic i-DC after CD40L stimulation did not affect their differentiating and functional capacity. Our data indicate that acute myeloid leukemia cells can fully differentiate into functionally competent m-DC and lay the ground for testing their efficacy as a tumor vaccine.}, } @article {pmid15289310, year = {2004}, author = {Fernández-Madrid, F and Tang, N and Alansari, H and Granda, JL and Tait, L and Amirikia, KC and Moroianu, M and Wang, X and Karvonen, RL}, title = {Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer.}, journal = {Cancer research}, volume = {64}, number = {15}, pages = {5089-5096}, doi = {10.1158/0008-5472.CAN-03-0932}, pmid = {15289310}, issn = {0008-5472}, mesh = {Annexins/*immunology ; Antibodies, Monoclonal ; Autoantibodies/*blood ; Autoantigens/*immunology ; Autoimmune Diseases/immunology/metabolism/pathology ; Breast Neoplasms/*diagnosis ; Carcinoma, Ductal, Breast/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Female ; Humans ; Middle Aged ; Peptide Library ; }, abstract = {We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.}, } @article {pmid15285807, year = {2004}, author = {Ridolfi, R and Riccobon, A and Galassi, R and Giorgetti, G and Petrini, M and Fiammenghi, L and Stefanelli, M and Ridolfi, L and Moretti, A and Migliori, G and Fiorentini, G}, title = {Evaluation of in vivo labelled dendritic cell migration in cancer patients.}, journal = {Journal of translational medicine}, volume = {2}, number = {1}, pages = {27}, pmid = {15285807}, issn = {1479-5876}, abstract = {BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with 99mTc-HMPAO or 111In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20-60 min after inoculation and the maximum concentration was reached after 48-72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC.}, } @article {pmid15279632, year = {2004}, author = {Sastre-Garau, X and Genin, P and Rousseau, A and Al Ghuzlan, A and Nicolas, A and Fréneaux, P and Rosty, C and Sigal-Zafrani, B and Couturier, J and Thiery, JP and Magdelénat, H and Vincent-Salomon, A}, title = {Increased cell size and Akt activation in HER-2/neu-overexpressing invasive ductal carcinoma of the breast.}, journal = {Histopathology}, volume = {45}, number = {2}, pages = {142-147}, doi = {10.1111/j.1365-2559.2004.01899.x}, pmid = {15279632}, issn = {0309-0167}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Case-Control Studies ; Cell Membrane/metabolism/pathology ; Cell Nucleus ; Cell Size ; DNA, Neoplasm/analysis ; Female ; Humans ; Image Processing, Computer-Assisted ; In Situ Hybridization, Fluorescence ; Protein Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Receptor, ErbB-2/*metabolism ; }, abstract = {AIMS: To determine whether cell size is related to HER-2/neu status and/or to Akt activation in breast carcinomas. HER-2/neu overexpression is observed in 20-30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/neu activation. Akt has been found to be involved in the HER-2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models.

METHODS AND RESULTS: A case-control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER-2/neu overexpression and 20 HER-2/neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin-fixed histological sections using an anti-phosphorylated-Akt (Ser473) antibody.

RESULTS: HER-2/neu-overexpressing carcinomas had a mean nuclear size of 75 +/- 22.2 micro m(2) and a mean cytoplasmic size of 187 +/- 52.3 micro m(2). Both values were higher than the nuclear and cytoplasmic size of HER-2/neu-negative cases (nucleus = 58 +/- 24.5 micro m(2), cytoplasm = 133 +/- 56.6 micro m(2); P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 micro m(2) were HER-2/neu-positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER-2/neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER-2/neu-positive and in 10% (2/19) of HER-2/neu-negative cases (P = 0.02).

CONCLUSIONS: HER-2/neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER-2/neu-overexpressing breast carcinomas may provide useful information for optimized individual HER-2/neu-targeted therapy.}, } @article {pmid15277404, year = {2004}, author = {Rivas-Carvalho, A and Meraz-Ríos, MA and Santos-Argumedo, L and Bajaña, S and Soldevila, G and Moreno-García, ME and Sánchez-Torres, C}, title = {CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines.}, journal = {International immunology}, volume = {16}, number = {9}, pages = {1251-1263}, doi = {10.1093/intimm/dxh127}, pmid = {15277404}, issn = {0953-8178}, mesh = {Cytokines/*physiology ; Dendritic Cells/*physiology ; Humans ; Immunophenotyping ; Interferon-gamma/biosynthesis ; Interleukin-10/biosynthesis ; Interleukin-12/biosynthesis ; Interleukin-4/biosynthesis ; Lymphocyte Activation ; Monocytes/*cytology ; Receptors, IgG/*analysis ; Th2 Cells/*immunology ; }, abstract = {We previously demonstrated that tumor necrosis factor (TNF)-alpha-matured CD16- and CD16+ human monocyte-derived dendritic cells (16-mDC and 16+mDC) differentially stimulate naive CD4+ lymphocytes by inducing Th1- and Th2-like responses, respectively. Here, we further characterized the role of different DC maturation factors on Th polarization. Immature 16+mDC and 16-mDC (iDC) obtained by culture of purified monocytes with GM-CSF and IL-4 were maturated with (i) Toll-like receptor (TLR) ligands [lipopolysaccharide (LPS)], (ii) lymphocyte-derived (soluble CD40 ligand, IFN-gamma) and (iii) endogenous inflammatory stimuli [TNF-alpha, prostaglandin (PG)E2]. After activation with these stimuli, DC secrete IL-12 only in presence of LPS, and 16+mDC produced lower amounts of IL-12 and IL-10 than 16-mDC. Allogeneic CD4+CD45RO- lymphocytes co-cultured with 16+mDC secreted higher levels of IL-4 and IL-10 than those co-cultured with 16-mDC, regardless of the maturation stimuli. Results were similar when DC were activated with TLR-2 or TLR-3 ligands. The higher induction of IL-4 by 16+mDC was primarily dependent on IL-12, IL-4 and IL-10. IFN-gamma production by CD4+ T cells was similar with all the conditions except with LPS-16+mDC, which induced reduced amounts of this cytokine. Those differences were totally eliminated by neutralization of IL-12, IL-4 or IL-10. Finally, 16-mDC could reverse the Th2 phenotype of already committed lymphocytes toward a Th1 pattern in short-term cultures, whereas 16+mDC had less ability to skew this phenotype. These results indicate that 16+mDC elicit superior Th2 responses independently of the maturation factors that they received, and suggest that they could represent an important population of regulatory DC.}, } @article {pmid15260850, year = {2004}, author = {Simooka, H and Oyama, T and Sano, T and Horiguchi, J and Nakajima, T}, title = {Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis.}, journal = {Pathology international}, volume = {54}, number = {8}, pages = {595-602}, doi = {10.1111/j.1440-1827.2004.01668.x}, pmid = {15260850}, issn = {1320-5463}, mesh = {14-3-3 Proteins ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Exonucleases/*metabolism ; Exoribonucleases ; Female ; Humans ; Hyperplasia/metabolism/pathology ; Immunoenzyme Techniques ; Neoplasm Proteins/*metabolism ; Precancerous Conditions/*metabolism/pathology ; }, abstract = {In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.}, } @article {pmid15256443, year = {2004}, author = {Ford, CE and Faedo, M and Crouch, R and Lawson, JS and Rawlinson, WD}, title = {Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women.}, journal = {Cancer research}, volume = {64}, number = {14}, pages = {4755-4759}, doi = {10.1158/0008-5472.CAN-03-3804}, pmid = {15256443}, issn = {0008-5472}, mesh = {Adult ; Aged ; Animals ; Breast/cytology ; Breast Neoplasms/genetics/*virology ; Breast Neoplasms, Male/genetics/*virology ; Carcinoma in Situ/genetics/virology ; Carcinoma, Ductal/genetics/virology ; Cell Transformation, Viral/*genetics ; Cohort Studies ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Male ; Mammary Tumor Virus, Mouse/*genetics ; Mice ; Middle Aged ; NIH 3T3 Cells ; Precancerous Conditions/genetics/*virology ; Sex Factors ; }, abstract = {Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.}, } @article {pmid15256368, year = {2004}, author = {Del Corsso, C and de Carvalho, AC and Martino, HF and Varanda, WA}, title = {Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {287}, number = {5}, pages = {H1928-36}, doi = {10.1152/ajpheart.00044.2004}, pmid = {15256368}, issn = {0363-6135}, mesh = {Action Potentials ; Adrenergic beta-Agonists/pharmacology ; Adult ; Aged ; Animals ; Autoantibodies/*blood ; Calcium Channels, L-Type/drug effects/*metabolism ; Cardiomyopathy, Dilated/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Isoproterenol/pharmacology ; Male ; Middle Aged ; Myocytes, Cardiac/*metabolism ; Patch-Clamp Techniques ; Rabbits ; Reaction Time ; Receptor, Muscarinic M2/*immunology ; Receptors, Adrenergic, beta-1/*immunology ; }, abstract = {Autoantibodies against muscarinic and adrenergic receptors have been found in the sera of patients with idiopathic dilated cardiomyopathy (IDC) and Chagas disease, but it is still unclear whether they can functionally interact with their respective receptors to modulate cardiac functions. In this study, our goal was to detect the presence of those antibodies in the sera of patients with IDC and characterize their electrophysiological effects on cardiomyocytes from rabbits. By using ELISA immunoassays, we detected high titers of antibodies against muscarinic M2 receptors in the sera of all IDC patients, whereas the detection of antibodies against the beta1-receptor occurred in 50% of them. Electrophysiological experiments using the whole cell configuration of the patch-clamp technique showed that sera from 43% of IDC patients induced a significant decrease (approximately 26%) in isoproterenol-stimulated L-type Ca2+ currents in rabbit ventricular myocytes, whereas the sera from healthy blood donors failed to do so. As expected, IDC sera also decreased the action potential duration (by 10.5%) due to a shortening of the plateau phase. Sera that reduced isoproterenol-stimulated L-type Ca2+ currents did not cause any effect on K+ currents. We conclude that sera from IDC patients have autoantibodies, which interact with muscarinic M2 receptors of rabbit cardiomyocytes, acting in an agonist-like fashion. This action results in changes in electrogenesis, which, as often observed in patients with IDC, could initiate ventricular arrhythmias that lead to sudden death.}, } @article {pmid15253443, year = {2004}, author = {Zang, L and Palmer Toy, D and Hancock, WS and Sgroi, DC and Karger, BL}, title = {Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling.}, journal = {Journal of proteome research}, volume = {3}, number = {3}, pages = {604-612}, doi = {10.1021/pr034131l}, pmid = {15253443}, issn = {1535-3893}, support = {GM 15847/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cattle ; Chromatography, Liquid ; Female ; Humans ; Lasers ; Mass Spectrometry ; Microdissection ; Molecular Sequence Data ; Oxygen Isotopes/*chemistry ; *Proteome ; Serum Albumin, Bovine/analysis/chemistry ; Trypsin/chemistry ; *Up-Regulation ; }, abstract = {The goal of this study was the development of a method for quantitative expression proteomics on the limited sample amounts obtained through laser capture microdissection (LCM) of tissues, e.g., approximately 10 000 cells, which typically contain roughly 1-4 microg protein. The 16O/18O labeling method was selected as an approach to measure differential expression. A sample preparation protocol including lysis, digestion and 16O/18O labeling was first developed for LCM cell samples. The selected protocol was examined using two LCM caps of 10 000 cells from invasive ductal carcinoma of the breast and shown to be repeatable. A further test of LC-IT-MS/MS in combination with the 16O/18O post-digestion labeling method for studying low level samples was conducted first on a single protein (BSA) and then on a 5-standard protein mixture digest of different protein amounts, each with a total content approximately 1 microg. Next, protein expression was compared between 10 000 cells, each of microdissected normal ductal epithelium and metastatic ductal carcinoma, using the developed method. The proteins from the microdissected cells were extracted, precipitated, digested with trypsin and then 16O/18O labeled. The normal and metastatic cell samples were analyzed using reversed phase LC-ESI-MS/MS on the ion trap mass spectrometer. A total of 76 proteins were identified. Some, such as mitochondrial isocitrate dehydrogenase, actin and 14-3-3 protein xi/delta were found to be significantly up-regulated in the breast tumor cells.}, } @article {pmid15252843, year = {2004}, author = {Desruisseau, S and Palmari, J and Giusti, C and Romain, S and Martin, PM and Berthois, Y}, title = {Clinical relevance of amphiregulin and VEGF in primary breast cancers.}, journal = {International journal of cancer}, volume = {111}, number = {5}, pages = {733-740}, doi = {10.1002/ijc.20312}, pmid = {15252843}, issn = {0020-7136}, mesh = {Adult ; Aged ; Amphiregulin ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Disease Progression ; EGF Family of Proteins ; Enzyme-Linked Immunosorbent Assay ; Female ; Glycoproteins/*analysis/*biosynthesis/pharmacology ; Humans ; Intercellular Signaling Peptides and Proteins/*analysis/*biosynthesis/pharmacology ; Middle Aged ; Multivariate Analysis ; Postmenopause ; Premenopause ; Prognosis ; Retrospective Studies ; Vascular Endothelial Growth Factor A/*analysis/*biosynthesis/pharmacology ; }, abstract = {The characterization of novel prognostic markers in breast cancer is necessary to improve the identification of high-risk populations. In our study, the prognostic significance of VEGF and amphiregulin (AR) was investigated and compared to conventional prognostic factors in primary breast cancers. The analysis was performed using enzyme-linked immuno-assay in a series of 193 patients, and univariate and multivariate analysis were performed in the overall population as well as in pre- and post-menopausal patients subdivided in node-negative (N-) and node-positive (N+) subsets. AR (median, 44.8 pg/mg protein) appeared strongly correlated with progesterone receptors (PgR) (p = 0.0018) in the premenopausal N+ population, and with uPA (p= 0.020) and VEGF (p= 0.0053) in the postmenopausal/N+ patients. Despite these attractive data, AR expression was not significant for recurrence or survival outcome. Data revealed strong correlation between VEGF and uPA, and PAI-1, in the N+ population. Moreover, patients with high VEGF levels displayed poor outcome, with an increased risk for N+ subset. These data were confirmed by multivariate analysis that presented histologic grade (HR, 10.55, p = 0.001) and VEGF (HR, 3.89, p = 0.03) as the prominent prognostic markers for overall survival for the N+ population. Furthermore, infiltrating ductal carcinomas (IDC) were shown to express higher levels of both uPA (p < 0.0001) and VEGF (p = 0.002) than intralobular carcinomas. This retrospective study reinforces the pejorative biological role of VEGF in the progression of breast tumors. Our data also suggest that VEGF and uPA might play particular role in the biology and progression of IDC.}, } @article {pmid15246916, year = {2004}, author = {Högye, M and Mándi, Y and Csanády, M and Sepp, R and Buzás, K}, title = {Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {94}, number = {2}, pages = {249-251}, doi = {10.1016/j.amjcard.2004.03.078}, pmid = {15246916}, issn = {0002-9149}, mesh = {Aged ; Cardiomyopathy, Dilated/*blood ; Cardiomyopathy, Hypertrophic/*blood/physiopathology ; Female ; Humans ; Interleukin-6/*blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/*analysis ; Ventricular Function, Left/physiology ; }, abstract = {It is known from the literature that the circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are elevated in heart failure and idiopathic dilated cardiomyopathy (IDC). Few convincing data are available on the production of cytokines in hypertrophic cardiomyopathy (HC). The levels of circulating IL-6, the soluble form of the IL-6 receptor (sIL-6R), and TNF-alpha in 19 patients with HC, 31 patients with IDC, and 20 healthy subjects (control group) were examined and compared with their clinical parameters. The levels of TNF-alpha and circulating IL-6 proved to be elevated in the sera of patients with IDC. In contrast, the level of TNF-alpha was not elevated in HC, although the levels of IL-6 and sIL-6R were significantly higher than those in the sera of patients with IDC. Although elevated levels of IL-6 may correlate with the extent of left ventricular dysfunction in IDC, the markedly elevated IL-6 levels did not correlate with left ventricular function in HC. The markedly elevated TNF-alpha levels in IDC were associated with the elevated IL-6 levels, probably because of an inflammatory process and/or heart failure. In contrast, in HC, in which the New York Heart Association functional class was actually good, the even higher IL-6 and sIL-6R levels were not associated with a TNF-alpha elevation. In HC, the IL-6 and sIL-6R elevations were due to another mechanism, probably by way of the cardiotrophin-associated gp130 receptor. The sources of IL-6 production in HC are not clear yet.}, } @article {pmid15239795, year = {2004}, author = {Pelte, MF and Schwaller, J and Cerrato, C and Meier, CA}, title = {Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion.}, journal = {The breast journal}, volume = {10}, number = {4}, pages = {350-354}, doi = {10.1111/j.1075-122X.2004.21467.x}, pmid = {15239795}, issn = {1075-122X}, mesh = {ACTH Syndrome, Ectopic/*complications ; Adrenocorticotropic Hormone/analysis/blood/metabolism ; Arrhythmias, Cardiac/etiology ; Biopsy, Needle ; Bone Neoplasms/secondary ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/*secondary ; Cushing Syndrome/*complications ; Fatal Outcome ; Female ; Gene Expression Regulation, Neoplastic ; Heart Failure/etiology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver Neoplasms/secondary ; Lung Neoplasms/metabolism/secondary ; Middle Aged ; Pro-Opiomelanocortin/*biosynthesis/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.}, } @article {pmid15235131, year = {2003}, author = {Jinfeng, M and Kimura, W and Hirai, I and Sakurai, F and Moriya, T and Mizutani, M}, title = {Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis.}, journal = {International journal of gastrointestinal cancer}, volume = {34}, number = {1}, pages = {9-18}, pmid = {15235131}, issn = {1537-3649}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Female ; *Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin 5AC ; Mucin-6 ; Mucins/*biosynthesis ; Pancreatic Neoplasms/*genetics/*pathology ; Prognosis ; Survival Analysis ; }, abstract = {AIM/BACKGROUND: MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis.

METHODS: Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically.

RESULTS: The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival.

CONCLUSION: The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.}, } @article {pmid15233641, year = {2004}, author = {Leidenius, M and Krogerus, L and Tukiainen, E and von Smitten, K}, title = {Accuracy of axillary staging using sentinel node biopsy or diagnostic axillary lymph node dissection--a case-control study.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {112}, number = {4-5}, pages = {264-270}, doi = {10.1111/j.1600-0463.2004.apm11204-0506.x}, pmid = {15233641}, issn = {0903-4641}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/*surgery ; Case-Control Studies ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Metastasis/pathology ; Neoplasm Staging ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; *Sentinel Lymph Node Biopsy ; }, abstract = {We aimed to compare the accuracy of axillary staging in breast cancer between sentinel node biopsy (SNB) and axillary lymph node dissection (ALND). The prevalence of axillary metastases was studied in 166 breast cancer patients with SNB and pair-matched control patients with ALND. The matching factors included age of the patient and grade, histological type and histological size of the tumour. There were 37% of patients with axillary metastases in the SNB group and 31% in the ALND group. Altogether, 57 pairs were discordant in relation to axillary metastases. In 34 discordant pairs the SNB patient and in 23 the ALND patient had axillary metastases, p=ns. Among the 36 discordant pairs with invasive ductal carcinoma (IDC), axillary metastases were detected as often in the SNB and the ALND patients. In the 21 discordant pairs with other histological types, the SNB patient had axillary metastases in 16 pairs and the ALND patient in 5 pairs, p<0.03. SNB seems to be as accurate a method for axillary staging as ALND. However, SNB generated no upstaging effect in IDC, only in other histological tumour types.}, } @article {pmid15226612, year = {2004}, author = {Mieda, J and Ohaki, Y and Oguro, T and Shimizu, H and Akasaka, K and Kyomoto, A and Kurokawa, M and Arai, S and Mori, O and Okada, S and Kyono, S and Tanaka, N}, title = {Breast cancer with neuroendocrine differentiation detected by unique staining pattern of neoplastic cells in hercep test.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {71}, number = {3}, pages = {203-208}, doi = {10.1272/jnms.71.203}, pmid = {15226612}, issn = {1345-4676}, mesh = {Aged ; Aged, 80 and over ; *Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Carcinoma, Neuroendocrine/*diagnosis/genetics/pathology ; Female ; Humans ; Immunohistochemistry/*methods ; *Neoplasms, Multiple Primary ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/*analysis ; Trastuzumab ; }, abstract = {Hercep Test (DAKO) is an immunohistological screening kit to select cases of advanced breast cancer with indication for treatment with a humanized mouse monoclonal antibody to human epidermal growth factor receptor-2, trasthzumab (Herceptin). We report a case of an 84-year-old female with invasive ductal carcinoma of the right breast, whose neoplastic cells showed a unique staining pattern in Hercep Test. The cells showed an intracytoplasmic fine granular staining pattern, instead of the membranous pattern of typical breast cancer cells. This unique staining pattern suggested some special features of the neoplastic cells. This case was finally diagnosed as invasive ductal carcinoma with focal neuroendocrine differentiation by subsequent imunohistochemical and electron microscopic examinations. The neoplastic cells showed positive reactivity for grimelius stain, chromogranin A, synaptophysin, and neuronspecific enolase, as well as electron-dense neurosecretory granules (up to 150 nm in diameter). This unique staining pattern of the neoplastic cells with Hercep Test is a useful clue to detect breast cancer with neuroendocrine differentiation, which is likely to be missed in routine examination. Clinical and pathologic findings including immunohistochemical and ultrastructural findings of this case are reported, together with a brief review of the literature.}, } @article {pmid15223751, year = {2004}, author = {Chhieng, DC and Frost, AR and Niwas, S and Weiss, H and Grizzle, WE and Beeken, S}, title = {Intratumor heterogeneity of biomarker expression in breast carcinomas.}, journal = {Biotechnic & histochemistry : official publication of the Biological Stain Commission}, volume = {79}, number = {1}, pages = {25-36}, doi = {10.1080/10520290410001715237}, pmid = {15223751}, issn = {1052-0295}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/*pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; }, abstract = {Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA.}, } @article {pmid15222110, year = {2004}, author = {Yoshida, T and Horiguchi, J and Koibuchi, Y and Kanoh, T and Iijima, K and Yoshida, M and Kikuchi, M and Takata, D and Oyama, T and Iino, Y and Morishita, Y}, title = {[Metastatic breast cancer treated with trastuzumab and paclitaxel--a case report with clinically complete response].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {31}, number = {6}, pages = {907-910}, pmid = {15222110}, issn = {0385-0684}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/secondary/surgery ; Combined Modality Therapy ; Drug Administration Schedule ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/surgery ; Paclitaxel/administration & dosage ; Receptor, ErbB-2/biosynthesis ; Remission Induction ; Trastuzumab ; }, abstract = {A 60-year-old woman who had undergone a total glandectomy for non-invasive ductal carcinoma of the left breast at the age of 56 in another hospital had a local recurrence in the left preserved breast. The patient was referred to our hospital and underwent a mastectomy. After surgery, treatment of UFT and CPA was started. Seven months after surgery, metastasis occurred at the left supraclavicular lymph node, and CPA, THP-adriamycine and 5-FU therapy was started. Fourteen months after surgery, skin redness of the left upper arm, the left chest wall and contralateral breast, and a contralateral axillary lymph node swelling were recognized. Neither docetaxel nor mitoxantrone-combined therapy was effective. Trastuzumab therapy was started because of HER2 overexpression by immunohistochemistry, and partial response was received after 7 weeks. Four months later, multiple nodules in the chest wall were recognized, and weekly treatment of trastuzumab and paclitaxel was started. Skin redness and multiple nodules in the chest wall completely disappeared after 3 months. No recurrence has been found for 14 months.}, } @article {pmid15218691, year = {2004}, author = {Günhan, O and Kafousi, M and Kurt, B and Koutsopoulos, AV and Karslioğlu, Y and Stathopoulos, E and Celasun, B}, title = {Comparison of C-erbB2 (HER-2/Neu) immunohistochemistry results on invasive breast carcinomas. Experience of 2 Pathology departments in Turkey and Greece.}, journal = {Analytical and quantitative cytology and histology}, volume = {26}, number = {3}, pages = {151-154}, pmid = {15218691}, mesh = {Breast Neoplasms/*metabolism/*pathology ; Greece ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; Pathology/*standards ; Receptor, ErbB-2/*analysis ; Reproducibility of Results ; Turkey ; }, abstract = {OBJECTIVE: To compare c-erbB2 (HER-2/Neu) immunohistochemical staining results obtained in 2 pathology departments and evaluate the reproducibility of staining and assessments.

STUDY DESIGN: Ninety primary invasive ductal carcinoma cases constituted the material of this study. For concordant assessment, serial sections from the same tissue blocks were prepared in both Turkey and Greece and were sent to each other. Evaluation of c-erbB2 (HER-2/Neu) staining was done independently in 2 departments by experienced pathologists. Stained slides were evaluated semiquantitatively in Turkey and both semiquantitatively and automatically in Greece.

RESULTS: There was complete agreement on staining density in 58 (64.4%) cases in both centers. In 15 cases there were major discordances in staining degrees, and in 17 cases there was a major discordance. Hypothetical treatment decisions based on these results showed that 82% of patients would have been handled the same way.

CONCLUSION: Comparison of immunostaining patterns performed at 2 centers provided valuable data that may be used in the development of quality assurance policies. The present study showed the usefulness of multicenter comparative studies in initiating the development of guidelines.}, } @article {pmid15215807, year = {2004}, author = {Smilde, TD and Hillege, HL and Navis, G and Boomsma, F and de Zeeuw, D and van Veldhuisen, DJ}, title = {Impaired renal function in patients with ischemic and nonischemic chronic heart failure: association with neurohormonal activation and survival.}, journal = {American heart journal}, volume = {148}, number = {1}, pages = {165-172}, doi = {10.1016/j.ahj.2004.02.007}, pmid = {15215807}, issn = {1097-6744}, mesh = {Aged ; Cardiomyopathy, Dilated/*blood/complications/mortality ; Coronary Artery Disease/complications ; Female ; Glomerular Filtration Rate ; Heart Failure/*blood/etiology/mortality ; Humans ; Kidney Diseases/blood/*complications/physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Natriuretic Peptides/*blood ; Neurotransmitter Agents/*blood ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Survival Analysis ; }, abstract = {BACKGROUND: Renal dysfunction is a strong predictor of mortality in chronic heart failure (CHF). Most patients with CHF have atherosclerotic vascular disease, and several authors have suggested that impaired renal function is only a marker of advanced atherosclerosis. We compared renal function in patients with ischemic and nonischemic CHF and examined associations with prognosis and extent of neurohormonal activation.

METHODS: In a large survival study (1906 patients), patients with documented coronary artery disease (CAD, n = 995), were compared with patients with idiopathic dilated cardiomyopathy (IDC, n = 429). In a smaller substudy, plasma neurohormones were determined in 270 patients and 37 patients (CAD and IDC, respectively). All patients had advanced CHF (New York Heart Association functional class III-IV). At baseline, the mean patient age was 64 +/- 10 years, and the mean left ventricular ejection fraction was 0.26 +/- 0.08. The baseline glomerular filtration rate was calculated with the Cockcroft-Gault equation (GFRc).

RESULTS: GFRc was a strong predictor for mortality in both groups on multivariate analysis. The relative risk was 3.04 for patients with IDC (P < or =.01, for the lowest quartile < or =53 mL/min), and the relative risk for patients with CAD was 1.81 (P =.01 for the lowest quartile < or =42 mL/min). Plasma neurohormones showed a relation with GFRc in both groups.

CONCLUSIONS: GFRc is related to survival and plasma neurohormones in both patient groups. In patients with IDC, this association appears to be at least as strong as in patients with CAD.}, } @article {pmid15194021, year = {2004}, author = {Fauchier, L and Eder, V and Casset-Senon, D and Marie, O and Babuty, D and Cosnay, P and Fauchier, JP}, title = {Segmental wall motion abnormalities in idiopathic dilated cardiomyopathy and their effect on prognosis.}, journal = {The American journal of cardiology}, volume = {93}, number = {12}, pages = {1504-1509}, doi = {10.1016/j.amjcard.2004.02.062}, pmid = {15194021}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/*diagnostic imaging/physiopathology ; Electrocardiography ; Female ; Fourier Analysis ; Gated Blood-Pool Imaging ; Heart Ventricles/*diagnostic imaging/physiopathology ; Humans ; Hypokinesia/diagnostic imaging ; Male ; Middle Aged ; Myocardial Contraction/*physiology ; Predictive Value of Tests ; Prognosis ; Stroke Volume/physiology ; Technetium ; Ventricular Dysfunction/diagnostic imaging/physiopathology ; }, abstract = {There is considerable variability in segmental wall motion abnormalities and in the prognosis of idiopathic dilated cardiomyopathy (IDC). Radionuclide ventriculography with Fourier analysis was performed in 107 patients with angiographically proved IDC. Amplitude analysis located the wall motion abnormalities. Using phase analysis in the left and right ventricles, the interventricular delay between the mean phase of the right and left ventricles was used to assess interventricular dyssynchrony and SDs of the mean phase in each ventricle was used to assess intraventricular dyssynchrony. Hypokinesis was global in 56 patients (52%) and localized in the anteroseptal wall in 34 (32%), the inferior wall in 12 (11%), the anteroseptal and inferior walls in 2 (2%), and the lateral wall in 3 (3%). Patients with localized wall motion abnormalities had larger left ventricular (LV) end-diastolic diameters (70 +/- 9 vs 66 +/- 8 mm, p = 0.009) and lower LV ejection fractions (25 +/- 9% vs 31 +/- 12%, p = 0.005). Intraventricular dyssynchrony was lower in patients with global hypokinesis (SD of LV mean phase 67 +/- 35 vs 48 +/- 22 ms, p = 0.002). With a follow-up of 27 +/- 23 months, increased SD of the LV phase (p = 0.005), decreased right ventricular ejection fraction (p = 0.006), decreased LV ejection fraction (p = 0.04), and localized wall motion abnormality (p = 0.009) were independent predictors of cardiac death or worsening heart failure leading to heart transplantation. Thus, segmental wall motion abnormalities are frequent in IDC and are associated with severe systolic dysfunction and a worse prognosis.}, } @article {pmid15184996, year = {2004}, author = {Mori, T and Sugimoto, K and Taniguchi, T and Tsurusaki, M and Izaki, K and Konishi, J and Zamora, CA and Sugimura, K}, title = {Renal arteriovenous fistula with rapid blood flow successfully treated by transcatheter arterial embolization: application of interlocking detachable coil as coil anchor.}, journal = {Cardiovascular and interventional radiology}, volume = {27}, number = {4}, pages = {374-376}, doi = {10.1007/s00270-004-0068-7}, pmid = {15184996}, issn = {0174-1551}, mesh = {Aged ; Arteriovenous Fistula/physiopathology/*therapy ; Blood Flow Velocity ; Catheters, Indwelling ; Embolization, Therapeutic/*instrumentation/methods ; Female ; Humans ; Renal Artery/*abnormalities ; Renal Veins/*abnormalities ; Treatment Outcome ; }, abstract = {A 70-year-old woman presented to our outpatient clinic with a large idiopathic renal arteriovenous fistula (AVF). Transcatheter arterial embolization (TAE) using interlocking detachable coils (IDC) as an anchor was planned. However, because of markedly rapid blood flow and excessive coil flexibility, detaching an IDC carried a high risk of migration. Therefore, we first coiled multiple loops of a microcatheter and then loaded it with an IDC. In this way, the coil was well fitted to the arterial wall and could be detached by withdrawing the microcatheter during balloon occlusion ("pre-framing technique"). Complete occlusion of the afferent artery was achieved by additional coiling and absolute ethanol. This technique contributed to a safe embolization of a high-flow AVF, avoiding migration of the IDC.}, } @article {pmid15182249, year = {2004}, author = {Chen, L and Jondal, M}, title = {Endolysosomal processing of exogenous antigen into major histocompatibility complex class I-binding peptides.}, journal = {Scandinavian journal of immunology}, volume = {59}, number = {6}, pages = {545-552}, doi = {10.1111/j.1365-3083.2004.01426.x}, pmid = {15182249}, issn = {0300-9475}, mesh = {Animals ; Antigen Presentation/*immunology ; Dendritic Cells/*cytology/immunology ; Egg Proteins/immunology ; Endosomes/*immunology ; Female ; Flow Cytometry ; Histocompatibility Antigens Class I/*immunology ; Lysosomes/*immunology ; Ovalbumin/immunology ; Peptide Fragments ; }, abstract = {An alternative endolysosomal pathway has recently been suggested for the processing of MHC-I-binding peptides, and peptide/MHC-I complexes have been demonstrated in this compartment. However, it remains unclear where in the antigen-presenting cells such peptides are processed, in the endolysosomes themselves or in the proteasomal complex. Here, we have investigated this using monoclonal antibodies specific for the immunodominant SIINFEKL/Kb complex (25-D1) or for the carbohydrate part of Db- or Kb-binding glycopeptides in combination with inhibitors for classical and endolysosomal MHC-I-processing pathways. Alternative processing was detected in both wt and TAP1(-/-) immature DC (iDC) as the expression of SIINFEKL/Kb complexes on the surface of OVA-treated cells in the presence of Brefeldin A (BFA) or lactacystin and their absence in the presence of the lysosomotropic amines ammonium chloride, chloroquine and methylamine. Internalized Db- and Kb-binding glycopeptides, detected with high specificity using an anti-galabiose (Gal2) monoclonal antibody, were found to appear on the cell surface of BFA-treated cells after intracellular MHC-I-binding. Peptide exchange in Kb was demonstrated as the gradual appearance of SIINFEKL/Kb complexes on BFA-treated cells which earlier had been saturated with another Kb-binding peptide. Our data support the presence of a fully functional endolysosomal processing pathway in iDC guided by the chaperone function of MHC-I molecules.}, } @article {pmid15173084, year = {2004}, author = {Takahashi, H and Oda, T and Hasebe, T and Aoyagi, Y and Kinoshita, T and Konishi, M and Nakagohri, T and Inoue, K and Takahashi, S and Kawahira, H and Monden, M and Ochiai, A}, title = {Biologically different subgroups of invasive ductal carcinoma of the pancreas: Dpc4 status according to the ratio of intraductal carcinoma components.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {10}, number = {11}, pages = {3772-3779}, doi = {10.1158/1078-0432.CCR-03-0120}, pmid = {15173084}, issn = {1078-0432}, mesh = {Adenocarcinoma/pathology ; Adult ; Aged ; Carcinoma, Pancreatic Ductal/diagnosis/*pathology ; Cell Differentiation ; DNA-Binding Proteins/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Lasers ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diagnosis/*pathology ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Smad4 Protein ; Time Factors ; Trans-Activators/*biosynthesis ; }, abstract = {PURPOSE: Among invasive ductal carcinomas of the pancreas (IDCP), there is a morphologically characteristic subgroup accompanied by abundant intraductal carcinoma components (ICCs). With the aim of determining whether ICC-rich IDCP are biologically different from ICC-poor IDCP, the expression status of Dpc4 protein was analyzed.

EXPERIMENTAL DESIGN: A total of 43 IDCP was subdivided into two groups: (a). ICC-rich IDCP (ICCs area occupies >or=10% of the entire tumorous area); and (b). ICC-poor IDCP (with <10% of ICCs area). A total of 10 invasive carcinomas derived from intraductal papillary-mucinous neoplasms (ICs from IPMNs) were also analyzed. Each invasive and intraductal carcinoma area was then evaluated for Dpc4 protein status by immunohistochemistry.

RESULTS: In a total of 43 IDCP, there were 23 ICC-rich IDCP and 20 ICC-poor IDCP. Dpc4-positive immunostaining was observed in the invasive carcinoma component of ICC-rich IDCP, ICC-poor IDCP, and ICs from IPMN in 18 of 23 (78%), 4 of 20 (20%), and 7 of 10 (70%) cases, respectively. In the intraductal component, positive staining for Dpc4 was found in 20 of 23 (87%), 3 of 7 (41%), and 8 of 10 (80%) cases, respectively. Dpc4 expression was found in both the invasive and ICC components of ICC-rich IDCP, similar to that found in IC derived from IPMN, whereas the expression of Dpc4 was largely diminished in ICC-poor IDCP.

CONCLUSIONS: Morphologically distinct subgroups of invasive ductal carcinomas of the pancreas, namely ICC-rich IDCP and ICC-poor IDCP, are also biologically distinguishable as revealed by the differential expression of Dpc4.}, } @article {pmid15162424, year = {2004}, author = {Zehn, D and Cohen, CJ and Reiter, Y and Walden, P}, title = {Extended presentation of specific MHC-peptide complexes by mature dendritic cells compared to other types of antigen-presenting cells.}, journal = {European journal of immunology}, volume = {34}, number = {6}, pages = {1551-1560}, doi = {10.1002/eji.200324355}, pmid = {15162424}, issn = {0014-2980}, mesh = {Antigen Presentation/*immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Line, Tumor/immunology ; Cell Membrane/immunology ; Dendritic Cells/*immunology ; Epitopes/immunology ; HLA-A Antigens/*immunology ; Humans ; Kinetics ; Microscopy, Confocal ; Monocytes/immunology ; Peptide Fragments/immunology ; Receptors, Antigen, T-Cell/*immunology ; Recombinant Proteins/immunology ; Sodium Azide ; }, abstract = {Dendritic cells are known as the most potent antigen-presenting cells for the induction of T cell-mediated immune responses. To discriminate between the presentation of antigens and the co-stimulatory aspects of this high immunostimulatory capacity, we used recombinant antibodies with T cell receptor-like specificity to detect defined MHC-peptide complexes on living cells. Mature human dendritic cells (mDC) were compared with immature DC (iDC), monocytes, CD4(+) T lymphocytes, melanoma cells, T2 cells and B lymphoblastoid cells for their capacity to present MHC class I-restricted tumor-associated T cell epitopes and were found to display the specific peptides two to six times longer than other cells. The most short-lived peptide had an average half-life of 8.7 h on mDCvs. 3.5 h on B lymphoblastoid cells, while the most long-lived peptide had a half-life of 118.5 h vs. 20.7 h on these two cell types. The decay kinetics of specific MHC-peptide complexes on iDC were among the fastest observed. The high potency of dendritic cells to induce specific T cell responses is thus based, in addition to the expression of co-stimulatory molecules, on an extended antigenic memory, which increases the likelihood and the extent of contacts between dendritic cells and antigen-specific T cells.}, } @article {pmid15154643, year = {2004}, author = {Toga, T and Nio, Y and Hashimoto, K and Higami, T and Maruyama, R}, title = {The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome.}, journal = {Anticancer research}, volume = {24}, number = {2C}, pages = {1173-1178}, pmid = {15154643}, issn = {0250-7005}, mesh = {Aged ; Carcinoma, Pancreatic Ductal/genetics/*metabolism/pathology/surgery ; Chemotherapy, Adjuvant ; DNA-Binding Proteins/*biosynthesis/genetics ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatic Neoplasms/genetics/*metabolism/pathology/surgery ; RNA, Messenger/*biosynthesis/genetics ; Smad4 Protein ; Trans-Activators/*biosynthesis/genetics ; Treatment Outcome ; }, abstract = {BACKGROUND: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated in about half of invasive ductal carcinoma (IDC) of the pancreas, but the expression of DPC4-mRNA remains to be evaluated. The present study assessed the comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their implication for patient outcome.

MATERIALS AND METHODS: In the freshly separated specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs, the expression of mRNA was assessed by in situ hybridization and the expression of pDpc4 was assessed by immunohistochemistry.

RESULTS: In the freshly separated specimens, DPC4-mRNA was expressed in 71% of the IDC, but pDpc4 expression was lost in 76% of the IDC. In 88 resectable IDCs, pDpc4 expression was lost in 75 (85.2%) and loss of pDpc4 expression was significantly correlated with the grade of nodal involvement (p =0.0265). Furthermore, the survival rate of the pDpc4 (-) group was significantly lower than that of the pDpc4 (+) group (p=0.0391). Adjuvant chemotherapy (ACT) significantly improved the survival rate and, in the ACT group, pDpc4 (-) patients had a significantly lower survival rate than the pDpc4 (+) patients.

CONCLUSION: In human pancreatic IDC, although DPC4-mRNA was usually expressed, the expression of pDpc4 was lost. The expression of pDpc-4 is an indicator of better prognosis and response to ACT.}, } @article {pmid15151696, year = {2004}, author = {Goulter, AB and Goddard, MJ and Allen, JC and Clark, KL}, title = {ACE2 gene expression is up-regulated in the human failing heart.}, journal = {BMC medicine}, volume = {2}, number = {}, pages = {19}, pmid = {15151696}, issn = {1741-7015}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Angiotensin-Converting Enzyme 2 ; Carboxypeptidases/*genetics ; Cardiomyopathy, Dilated/*enzymology ; Child, Preschool ; Female ; *Gene Expression ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*enzymology ; Myocardium/*enzymology ; Peptidyl-Dipeptidase A ; *Up-Regulation ; }, abstract = {BACKGROUND: ACE2 is a novel homologue of angiotensin converting enzyme (ACE). ACE2 is highly expressed in human heart and animal data suggest that ACE2 is an essential regulator of cardiac function in vivo. Since overactivity of the renin-angiotensin system contributes to the progression of heart failure, this investigation assessed changes in gene expression of ACE2, ACE, AT1 receptor and renin in the human failing heart.

METHODS: The sensitive technique of quantitative reverse transcriptase polymerase chain reaction was used to determine the level of mRNA expression of ACE and ACE2 in human ventricular myocardium from donors with non-diseased hearts (n = 9), idiopathic dilated cardiomyopathy (IDC, n = 11) and ischemic cardiomyopathy (ICM, n = 12). Following logarithmic transformation of the data, a one-way analysis of variance was performed for each target gene followed by a Dunnett's test to compare the two disease groups IDC and ICM versus control.

RESULTS: As anticipated, ACE mRNA was found to be significantly increased in the failing heart with a 3.1 and 2.4-fold up-regulation found in IDC and ICM relative to non-diseased myocardium. Expression of ACE2 mRNA was also significantly up-regulated in IDC (2.4-fold increase) and ICM (1.8-fold increase) versus non-diseased myocardium. No change in angiotensin AT1 receptor mRNA expression was found in failing myocardium and renin mRNA was not detected.

CONCLUSIONS: These data suggest that ACE2 is up-regulated in human IDC and ICM and are consistent with the hypothesis that differential regulation of this enzyme may have important functional consequences in heart failure. This strengthens the hypothesis that ACE2 may be a relevant target for the treatment of heart failure and will hopefully spur further studies to clarify the functional effects in human myocardium of ACE2 derived peptides.}, } @article {pmid15143932, year = {2004}, author = {Suzuki, K and Aiura, K and Kitagou, M and Hoshimoto, S and Takahashi, S and Ueda, M and Kitajima, M}, title = {Platelets counts closely correlate with the disease-free survival interval of pancreatic cancer patients.}, journal = {Hepato-gastroenterology}, volume = {51}, number = {57}, pages = {847-853}, pmid = {15143932}, issn = {0172-6390}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Ductal/*blood/pathology/surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/*blood/pathology/surgery ; *Platelet Count ; Postoperative Care ; Preoperative Care ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND/AIMS: We investigated the relationship between preoperative platelets count and the outcome of pancreatic cancer patients.

METHODOLOGY: We retrospectively reviewed the clinical records of 105 patients with invasive ductal carcinoma of the pancreas who underwent radical resection at our institution over a 20-year period. The patients were divided into two groups based on their preoperative platelets counts: a group with thrombocytosis (> or = 40x10(4)/mL) and a group with non-elevated platelets counts (< 40x10(4)/mL). Histopathological findings, survival rates, recurrence patterns, and disease-free survival intervals were compared between the two groups.

RESULTS: The outcome of the group with thrombocytosis was significantly poorer than that of the group with non-elevated platelets counts (p=0.043). The mean disease-free interval of patients with thrombocytosis was 4.9 months as opposed to 46.5 months for those with non-elevated platelets counts (p=0.006). Patients were classified into four groups according to changes in platelets counts after surgery. Consistently, the outcome of the group with both pre- and postoperative non-elevated platelets counts was the best compared to groups with post- and/or postoperative thrombocytosis.

CONCLUSIONS: Our clinical data suggest that high platelets counts in the preoperative and postoperative period may be associated with a poor outcome and shortening of postoperative disease-free survival interval.}, } @article {pmid15142882, year = {2004}, author = {Bengtsson, AK and Ryan, EJ and Giordano, D and Magaletti, DM and Clark, EA}, title = {17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells.}, journal = {Blood}, volume = {104}, number = {5}, pages = {1404-1410}, doi = {10.1182/blood-2003-10-3380}, pmid = {15142882}, issn = {0006-4971}, support = {AI 44257/AI/NIAID NIH HHS/United States ; DE 13061/DE/NIDCR NIH HHS/United States ; RR 00166/RR/NCRR NIH HHS/United States ; }, mesh = {CD40 Antigens/metabolism ; Cell Movement/drug effects/immunology ; Cell Survival/drug effects/immunology ; Cells, Cultured ; Chemokine CCL17 ; Chemokine CCL19 ; Chemokine CCL2/metabolism ; Chemokine CCL22 ; Chemokines, CC/metabolism/pharmacology ; Cytokines/*metabolism ; Dendritic Cells/cytology/*drug effects/*metabolism ; Estradiol/*immunology/*pharmacology ; Glycoproteins/metabolism ; Humans ; Immunophenotyping ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Lipopolysaccharides/pharmacology ; Monocytes/cytology ; Osteoprotegerin ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Tumor Necrosis Factor ; }, abstract = {The effects of estrogen on the immune system are still largely unknown. We have investigated the effect of 17beta-estradiol (E(2)) on human monocyte-derived immature dendritic cells (iDCs). Short-term culture in E(2) had no effect on iDC survival or the expression of cell surface markers. However, E(2) treatment significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E(2) significantly increased secretion of the inflammatory chemokines IL-8 and monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the constitutive chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). However, after E(2) pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced. Moreover, mature DCs pretreated with E(2) stimulated T cells better than control cells. Finally, we found that E(2) provides an essential signal for migration of mature DCs toward CCL19/macrophage inflammatory protein 3beta (MIP3beta). In summary, E(2) may affect DC regulation of T-cell and B-cell responses, as well as help to sustain inflammatory responses. This may explain, in part, the reason serum levels of estrogen correlate with the severity of certain autoimmune diseases.}, } @article {pmid15140777, year = {2004}, author = {Radstake, TR and van Lent, PL and Pesman, GJ and Blom, AB and Sweep, FG and Rönnelid, J and Adema, GJ and Barrera, P and van den Berg, WB}, title = {High production of proinflammatory and Th1 cytokines by dendritic cells from patients with rheumatoid arthritis, and down regulation upon FcgammaR triggering.}, journal = {Annals of the rheumatic diseases}, volume = {63}, number = {6}, pages = {696-702}, pmid = {15140777}, issn = {0003-4967}, mesh = {Arthritis, Rheumatoid/immunology/*metabolism ; Cytokines/*biosynthesis ; Dendritic Cells/*metabolism ; Down-Regulation/immunology ; Enzyme-Linked Immunosorbent Assay/methods ; Flow Cytometry/methods ; Humans ; Interferon-gamma/biosynthesis ; Interleukins/biosynthesis ; Radioimmunoassay/methods ; Receptors, IgG/*immunology ; Tumor Necrosis Factor-alpha/biosynthesis ; }, abstract = {OBJECTIVE: To assess whether DC from RA produce altered cytokine levels and whether this is regulated by triggering of Fc gamma receptors (FcgammaR).

METHODS: The production of proinflammatory (TNFalpha, IL1, IL6), Th1 (IL12, IFNgamma), and Th2 (IL10) cytokine profiles of immature DC (iDC) from patients with RA and healthy subjects upon triggering of FcgammaR dependent and independent pathways was investigated. iDC, derived from blood monocytes by standardised protocols, were stimulated with immune complexes (IC) at day 6 for 48 hours and, subsequently, for 2 days with LPS in the presence or absence of IC or IFNgamma, resulting in fully matured DC (mDC). IL1, IL6, TNFalpha, IFNgamma, IL12, and IL10 levels in supernatants were measured by ELISA and RIA.

RESULTS: mDC from patients with RA showed a markedly increased production of IL1, IL6, TNFalpha, and IL10 compared with DC from healthy donors. Triggering of FcgammaR decreased the production of proinflammatory cytokines IL1, IL12, and IFNgamma by iDC and mDC in RA and controls. The production of IL6 and TNFalpha decreased in patients with RA, whereas it was increased in controls. Triggering of FcgammaR independent mechanisms using IFNgamma increased the production of proinflammatory and Th1 cytokines, which was more pronounced in RA.

CONCLUSION: FcgammaR dependent pathways influence cytokine production by DC. A skewed balance towards proinflammatory and Th1 cytokines in RA can, at least partly, be restored by triggering FcgammaR on DC in RA. Insight into the mechanism which determines the FcgammaR balance might lead to new strategies to abrogate Th1 driven inflammatory processes in RA.}, } @article {pmid15137212, year = {2004}, author = {Weber, P and Eriksson, J and Seewer, S}, title = {Medical activities and statistics.}, journal = {Medicinski arhiv}, volume = {58}, number = {1 Suppl 2}, pages = {86-87}, pmid = {15137212}, mesh = {*Hospital Information Systems ; *International Classification of Diseases ; Medical Informatics Computing ; Software ; Switzerland ; }, abstract = {The evaluation of the medical activity is a major concern for hospitals and public health services. With the introduction of coding (IDC-10 and CHOP classifications) hospitals are now able to analyze their medical activity. A way to improve physicians' acceptance in analyzing their work is to give them valuable feedback information. Building statistics tools is costly and time consuming. Therefore introducing data warehouse tools is helpful. Nice Code is an easy-to-use software that helps medical encoding while immediately offering understandable statistics. In Switzerland, physicians demand real feedback based on the data transmitted at the "cantonal" or federal levels and more transparency in third payer's decisions. In this respect, several cantons decided to equip public health services and hospitals with this tool. The goal is to give, physicians and economists, powerful tools for analyzing the medical activity.}, } @article {pmid15129910, year = {2004}, author = {Shen, SS and Sahin, AA}, title = {Invasive ductal carcinoma of the breast with a microglandular adenosis pattern.}, journal = {Annals of diagnostic pathology}, volume = {8}, number = {1}, pages = {39-42}, doi = {10.1016/j.anndiagpath.2003.11.009}, pmid = {15129910}, issn = {1092-9134}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; Diagnosis, Differential ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Middle Aged ; }, abstract = {Invasive breast carcinomas of special type are composed of up to 35% of all cases, such as tubular carcinoma, mucinous carcinoma, invasive cribriform carcinoma, lobular carcinoma, metaplastic carcinoma, medullary carcinoma, and other rare variants. They are recognized by their specific growth and morphologic patterns, glandular differentiation, and cytologic and nuclear features. These features are also present as a focal or minor component in many carcinomas of no special type. In addition, there are a number of lesions that are mimickers of invasive carcinoma, which can sometimes create diagnostic difficulties. It is important for pathologists to recognize these histologic variants and mimickers of breast carcinoma, particularly in evaluating needle or core biopsies. We report a case of a 64-year-old woman with breast carcinoma of no special type with areas having features with resemblance to microglandular adenosis. Differential diagnosis and their histologic features are discussed.}, } @article {pmid15123465, year = {2004}, author = {Sabel, MS and Kaufman, CS and Whitworth, P and Chang, H and Stocks, LH and Simmons, R and Schultz, M}, title = {Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial.}, journal = {Annals of surgical oncology}, volume = {11}, number = {5}, pages = {542-549}, doi = {10.1245/ASO.2004.08.003}, pmid = {15123465}, issn = {1068-9265}, mesh = {Adult ; Aged ; Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Cryosurgery/adverse effects/*methods ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; *Neoplasm Staging ; *Pain, Postoperative ; Treatment Outcome ; }, abstract = {BACKGROUND: With recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.

METHODS: Twenty-nine patients with ultrasound-visible primary invasive breast cancer
RESULTS: Cryoablation was successfully performed in an office-based setting with only local anesthesia. There were no complications to the procedure or postprocedural pain requiring narcotic pain medications. Cryoablation successfully destroyed 100% of cancers <1.0 cm. For tumors between 1.0 and 1.5 cm, this success rate was achieved only in patients with invasive ductal carcinoma without a significant ductal carcinoma-in-situ (DCIS) component. For unselected tumors >1.5 cm, cryoablation was not reliable with this technique. Patients with noncalcified DCIS were the cause of most cryoablation failures.

CONCLUSIONS: Cryoablation is a safe and well-tolerated office-based procedure for the ablation of early-stage breast cancer. At this time, cryoablation should be limited to patients with invasive ductal carcinoma
RESULTS: The same RNA samples isolated from peripheral blood monocyte precursors and immature DC (iDC) were used for GeneChip microarray probing and SSH cDNA library construction. 10,000 clones from each of the two-way SSH libraries (iDC-monocytes and monocytes-iDC) were picked for sequencing. About 2000 transcripts were identified for each library from 8000 successful sequences. Only 70% to 75% of these transcripts were represented on the U95 series GeneChip microarrays, implying that 25% to 30% of these transcripts might not have been identified in a study based only on GeneChip microarrays. In addition, about 10% of these transcripts appeared to be "novel", although these have not yet been closely examined. Among the transcripts that are also represented on the chips, about a third were concordantly discovered as differentially regulated between iDC and monocytes by GeneChip microarray transcript profiling. The remaining two thirds were either not inferred as differentially regulated from GeneChip microarray data, or were called differentially regulated but in the opposite direction. This underscores the importance both of generating reciprocal pairs of SSH libraries, and of real-time RT-PCR confirmation of the results.

CONCLUSIONS: This study suggests that SSH could be used as an alternative and complementary transcript profiling tool to GeneChip microarrays, especially in identifying novel genes and transcripts of low abundance.}, } @article {pmid15110881, year = {2004}, author = {Arai, K and Teratani, T and Kuruto-Niwa, R and Yamada, T and Nozawa, R}, title = {S100A9 expression in invasive ductal carcinoma of the breast: S100A9 expression in adenocarcinoma is closely associated with poor tumour differentiation.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {40}, number = {8}, pages = {1179-1187}, doi = {10.1016/j.ejca.2004.01.022}, pmid = {15110881}, issn = {0959-8049}, mesh = {Adenocarcinoma/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Calgranulin B/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Female ; Humans ; Immunohistochemistry/methods ; Neoplasm Proteins/*metabolism ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; }, abstract = {S100A9 is associated with myelomonocytic cell differentiation and is also expressed in some epithelia. However, there have been few studies on S100A9 in adenocarcinoma (AC) because the expression in normal epithelia is limited to squamous epithelia. Our previous studies on pulmonary AC and liver carcinomas suggested that S100A9 expression in carcinomas of glandular cell origin is related to poor tumour differentiation. In this study, we examined S100A9 expression in invasive breast carcinoma and evaluated the relation of the expression to the tumour differentiation in 70 cases of invasive ductal carcinoma (IDC) of the breast. S100A9 gene and protein expression was detected in MCF-7 breast carcinoma cells. The rate of S100A9 immunopositivity in IDC showed a higher correlation with poor tumour differentiation, especially in nuclear pleomorphism (P=0.0002) and mitotic activity (P=0.0001). Furthermore, transcriptional expression of S100A9 in sections of IDC could be detected in cases with a high S100A9 immunopositivity. No significant differences in the number of myelomonocytic cells expressing S100A9 were found among cases. There was no correlation between S100A9 immunopositivity and lymph node metastasis (P=0.32). S100A9 immunopositivity in non-invasive ductal carcinoma was also associated with poor tumour differentiation. No immunopositive reaction was observed in invasive lobular carcinomas with a classic cytological appearance and non-neoplastic duct cells. We conclude that S100A9 in glandular epithelial cells is newly expressed under cancerous conditions and is over-expressed in poorly differentiated AC.}, } @article {pmid15108046, year = {2004}, author = {Lamy, O and Elmiger, H and Fiche, M and Bauer, J and Livio, F}, title = {Acquired hemophilia as first manifestation of breast carcinoma in a man under long-term spironolactone therapy.}, journal = {International journal of clinical oncology}, volume = {9}, number = {2}, pages = {130-133}, doi = {10.1007/s10147-003-0372-2}, pmid = {15108046}, issn = {1341-9625}, mesh = {Aged ; Antineoplastic Agents, Hormonal/therapeutic use ; Biopsy, Needle/methods ; Breast Neoplasms, Male/*chemically induced/diagnosis/therapy ; Carcinoma, Ductal, Breast/*chemically induced/diagnosis/therapy ; Diuretics/*adverse effects ; Hemophilia A/*etiology/therapy ; Humans ; Male ; Mammography ; Mastectomy/methods ; Paraneoplastic Syndromes/etiology ; Spironolactone/*adverse effects ; Tamoxifen/therapeutic use ; Treatment Outcome ; }, abstract = {A 69-year-old man under long-term spironolactone therapy (16 years) was hospitalized with spontaneous hematoma on the trunk and extremities. Coagulation studies disclosed an acquired hemophilia that was successfully treated with human factor VIII for a few days and immunosuppressive agents for several months. Physical examination revealed bilateral gynecomastia and an upper left quadrant breast nodule. Complete staging was unremarkable. Complete left mastectomy was performed. Histopathology showed invasive ductal carcinoma, expressing positivity for estrogen and progesterone receptors. The acquired hemophilia was considered to be a paraneoplasic syndrome. The question of a linkage between long-term spironolactone therapy and breast carcinoma is discussed.}, } @article {pmid15099140, year = {2004}, author = {Liberman, V}, title = {Local and global judgments of confidence.}, journal = {Journal of experimental psychology. Learning, memory, and cognition}, volume = {30}, number = {3}, pages = {729-732}, doi = {10.1037/0278-7393.30.3.729}, pmid = {15099140}, issn = {0278-7393}, mesh = {Humans ; *Judgment ; Surveys and Questionnaires ; }, abstract = {Studies of calibration have shown that people's mean confidence in their answers (local confidence) tends to be greater than their overall estimate of the percentage of correct answers (global confidence). Moreover, whereas the former exhibits overconfidence, the latter often exhibits underconfidence. Three studies present evidence that global underconfidence reflects a failure to make an allowance for correct answers that are likely to result from mere guessing and can be eliminated by informing participants of the dubious normative status of estimates below 50% (i.e., chance). Previously reported discrepancies between global and local confidence, it is concluded, arise less from possible methodological artifacts in assessment of local confidence than from normatively inappropriate assessments of global confidence.}, } @article {pmid15098783, year = {2004}, author = {Giron, GL and Friedman, I and Feldman, S}, title = {Lobular carcinoma in ectopic axillary breast tissue.}, journal = {The American surgeon}, volume = {70}, number = {4}, pages = {312-315}, pmid = {15098783}, issn = {0003-1348}, mesh = {Aged ; Axilla ; Biopsy, Needle ; *Breast ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Choristoma/*pathology/surgery ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphatic Diseases/*pathology/surgery ; Mammography ; Mastectomy/methods ; Risk Assessment ; Treatment Outcome ; }, abstract = {Accessory mammary tissue is reported to occur in 2 per cent to 6 per cent of women and results from failure of regression of a portion of the galactic band, which runs from the axilla to the groin during embryogenesis. The differential diagnosis of a mass located along the course of the primitive milk line must include accessory breast tissue. This tissue is subject to the same physiologic and pathologic changes as in the breast proper. There are numerous case reports of masses arising in accessory breast tissue ranging from fibroadenomas and phyllodes tumors to invasive mucinous adenocarcinoma. The predominant pathology, as with the pectoral breast, is that of invasive ductal carcinoma. We present the case of a lobular carcinoma arising in axillary ectopic breast tissue. Although this has previously been reported, it is a rare entity.}, } @article {pmid15093911, year = {2004}, author = {Thurman, SA and Schnitt, SJ and Connolly, JL and Gelman, R and Silver, B and Harris, JR and Recht, A}, title = {Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma.}, journal = {International journal of radiation oncology, biology, physics}, volume = {59}, number = {1}, pages = {152-159}, doi = {10.1016/j.ijrobp.2003.10.029}, pmid = {15093911}, issn = {0360-3016}, mesh = {Adenocarcinoma/mortality/pathology/*therapy ; Adenocarcinoma, Mucinous/mortality/pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/pathology/*therapy ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Carcinoma, Medullary/mortality/pathology/therapy ; Chemotherapy, Adjuvant ; Female ; Humans ; Logistic Models ; Lymph Node Excision ; Middle Aged ; Radiotherapy Dosage ; Radiotherapy, Adjuvant ; Retrospective Studies ; Treatment Outcome ; }, abstract = {PURPOSE: To evaluate the site of first failure of patients with early-stage tubular, mucinous, and medullary breast carcinoma after breast-conserving therapy and compare their results with those of patients with infiltrating ductal carcinoma (IDC).

METHODS AND MATERIALS: Twenty clinical Stage I and II patients with mucinous carcinoma, 27 with medullary carcinoma, 28 with tubular carcinoma, and 1055 with IDC were identified. The minimal potential follow-up was 10 years.

RESULTS: No statistically significant difference (p = 0.15) was seen in the site of first failure between the four histologic types within the first 10 years after treatment. When the IDC tumors were omitted from the comparison, the failure patterns of the remaining three histologic types were not significantly different (p = 0.31). In a polychotomous logistic model, histologic type was not significantly associated with the site of first failure (all p >0.17). Local failure was significantly associated with age <50 years (p = 0.04), positive surgical margins (p = 0.007), lymphovascular invasion (p = 0.04), and tumors with an extensive intraductal component (p <0.001). Regional/distant/opposite breast failure was significantly associated with clinical Stage T2 tumors (p <0.001), four or more positive lymph nodes (p = 0.004), and lymphovascular invasion-positive tumors (p <0.001). Second malignancy or death was significantly associated with age at diagnosis >60 years (p <0.001) and lymphovascular invasion-positive tumors (p = 0.03).

CONCLUSION: No statistically significant difference was noted in the site of first failure between patients with medullary, mucinous, or tubular carcinoma and patients with IDC. Although not statistically significant, we did note a trend toward a lower long-term rate of disease-free survival in patients with IDC.}, } @article {pmid15088247, year = {2004}, author = {Seifert, L and Boulesteix, L and Chollet, D}, title = {Effect of gender on the adaptation of arm coordination in front crawl.}, journal = {International journal of sports medicine}, volume = {25}, number = {3}, pages = {217-223}, doi = {10.1055/s-2003-45253}, pmid = {15088247}, issn = {0172-4622}, mesh = {Adaptation, Physiological ; Adolescent ; Adult ; Analysis of Variance ; Anthropometry ; Arm/*physiology ; Biomechanical Phenomena ; Female ; Humans ; Male ; Motor Skills ; Sex Factors ; Swimming/*physiology ; Videotape Recording ; }, abstract = {The aim of this study was to compare the arm coordination of 14 elite men swimmers and 10 elite women swimmers at eight different velocities, from the usual 3000 m velocity to their maximal velocity (V (max)). Each stroke phase was identified by video analysis and the Index of Coordination (IdC) was established. Three modes of coordination have been identified: catch-up (IdC < 0); opposition (IdC = 0); and superposition (IdC > 0). This study shows that at a greater individually imposed swim pace (ISP) elite men spontaneously adapt by opposing their arms during sprint time (IdC = +2.57 +/- 6 % at Vmax), whereas elite women (IdC = -3.88 +/- 6.1 % at V (max)) adapt more slowly, remaining in catch-up coordination. Elite men favoured the increase of propulsive actions by increasing the propulsive phases (pull and push phases) and decreasing the entry + catch phase, even if the recovery phase increased. Elite women generated less propulsive actions during sprint, i. e. shorter push and pull phases and a longer entry + catch phase. The biomechanical constraints (effective velocity: EV) could explain that men switched coordination at high velocity (sprint), whilst the differences between men and women at a similar EV related more to their motor organisation than to biomechanical constraints. Anthropometric data could partially explain this difference between genders. Height (171.6 +/- 5.8 cm vs. 185.5 +/- 4.2 cm) and arm span (177.12 +/- 6.24 cm vs. 192.75 +/- 1.83 cm) were smaller in women than in men. The women catch-up coordination was not a "worse coordination" when compared with that of men, but it reflected a different motor organisation resulting from different anthropometric properties and swimming technique. Therefore, catch-up coordination could be an individual response to different constraints.}, } @article {pmid15088179, year = {2004}, author = {Diekmann, F and Diekmann, S and Beljavskaja, M and Bick, U and Taupitz, M and Blohmer, JU and Winzer, KJ and Hamm, B}, title = {[Preoperative MRT of the breast in invasive lobular carcinoma in comparison with invasive ductal carcinoma].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {176}, number = {4}, pages = {544-549}, doi = {10.1055/s-2004-813011}, pmid = {15088179}, issn = {1438-9029}, mesh = {Breast/pathology ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging/surgery ; Carcinoma, Lobular/*diagnosis/diagnostic imaging/pathology/surgery ; Data Interpretation, Statistical ; Female ; Humans ; *Magnetic Resonance Imaging ; Mammography ; Preoperative Care ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: To evaluate the role of preoperative MRI of the breast in invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: For one year, all patients transferred by the hospital's gynecologic outpatient service for suspicious findings in routine mammography and/or ultrasound (conventional modalities = CM) underwent preoperative MRI of the breast. Retrospective analysis of the histologic findings identified 17 patients with ILC. These were compared with 30 proven IDC patients, chosen by random. The MRI findings of these 2 patient groups were compared with regard to the detection of additional lesions. The average number of additional lesions detected by MRI was compared for significant differences between both groups using the T-test for paired samples.

RESULTS: In the 17 patients with ILC, conventional modalities (CM) identified 21malignant lesions whereas MRI detected a total of 30 lesions. At least one additional lesion was detected by MRI in 7 of the 17 patients with ILC. In the 30 patients with IDC, on the other hand, MRI detected an additional lesion in three instances only. In one patient of the ILC group, MRI identified an additional lesion in the contralateral breast that had escaped detection by CM. No additional contralateral lesion was detected by MRI in any of the IDC patients. Benefit of MRI in ILC-Group: The mean numbers of detected malignant lesions differed significantly between diagnosis by MRI and CM in the ILC group (1.77 carcinomas per patient with MRI versus 1.24 with conventional modalities, T-test, p = 0.0078). Benefit of MRI in IDC-Group: although it was possible to find 1.27 carcinomas vs. 1.17 carcinomas per patient in the IDC-Group, this benefit was not statistical significant (T-test, p = 0.0831).

CONCLUSION: Preoperative MRI detects multiple additional lesions compared to the ones already known by CM. The higher incidence of multiple lesions in ILC compared to IDC and the difficult diagnosis of ILC in CM might be the reason for the fact that preoperative MRI is particularly useful in patients with ILC.}, } @article {pmid15084238, year = {2004}, author = {Arpino, G and Bardou, VJ and Clark, GM and Elledge, RM}, title = {Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {3}, pages = {R149-56}, pmid = {15084238}, issn = {1465-542X}, support = {P01 CA030195/CA/NCI NIH HHS/United States ; P50 CA058183/CA/NCI NIH HHS/United States ; P01 CA30195/CA/NCI NIH HHS/United States ; P50 CA58183/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/pathology/secondary ; Carcinoma, Lobular/chemistry/mortality/*pathology/secondary ; Disease-Free Survival ; ErbB Receptors/analysis ; Female ; Follow-Up Studies ; Humans ; Life Tables ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins/analysis ; Neoplasms, Hormone-Dependent/chemistry/mortality/pathology ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Analysis ; Survival Rate ; Treatment Outcome ; Tumor Suppressor Protein p53/analysis ; }, abstract = {INTRODUCTION: Invasive lobular carcinoma (ILC) comprises approximately 10% of breast cancers and appears to have a distinct biology. Because it is less common than infiltrating ductal carcinoma (IDC), few data have been reported that address the biologic features of ILC in the context of their clinical outcome. In the present study we undertook an extensive comparison of ILC and IDC using a large database to provide a more complete and reliable assessment of their biologic phenotypes and clinical behaviors.

METHODS: The clinical and biological features of 4140 patients with ILC were compared with those of 45,169 patients with IDC (not otherwise specified). The median follow-up period was 87 months.

RESULTS: In comparison with IDC, ILC was significantly more likely to occur in older patients, to be larger in size, to be estrogen and progesterone receptor positive, to have lower S-phase fraction, to be diploid, and to be HER-2, p53, and epidermal growth factor receptor negative. It was more common for ILC than for IDC to metastasize to the gastrointestinal tract and ovary. The incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (20.9% versus 11.2%; P < 0.0001). Breast preservation was modestly less frequent in ILC patients than in IDC patients. The 5-year disease-free survival was 85.7% for ILC and 83.5% for IDC (P = 0.13). The 5-year overall survival was 85.6% for ILC and 84.1% for IDC (P = 0.64).

CONCLUSION: Despite the fact that the biologic phenotype of ILC is quite favorable, these patients do not have better clinical outcomes than do patients with IDC. At present, management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.}, } @article {pmid15073245, year = {2004}, author = {Fukuchi, K and Yasumura, Y and Kiso, K and Hayashida, K and Miyatake, K and Ishida, Y}, title = {Gated myocardial SPECT to predict response to beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {45}, number = {4}, pages = {527-531}, pmid = {15073245}, issn = {0161-5505}, mesh = {Adrenergic beta-Antagonists/administration & dosage ; Adult ; Age Factors ; Aged ; Bisoprolol/*administration & dosage ; Carbazoles/*administration & dosage ; Cardiomyopathy, Dilated/complications/diagnosis/*diagnostic imaging/*drug therapy ; Carvedilol ; Drug Therapy, Combination ; Feasibility Studies ; Female ; Gated Blood-Pool Imaging/*methods ; Humans ; Male ; Middle Aged ; Prognosis ; Propanolamines/*administration & dosage ; Reproducibility of Results ; Risk Assessment/methods ; Sensitivity and Specificity ; Sex Factors ; Tomography, Emission-Computed, Single-Photon/*methods ; Treatment Outcome ; Ventricular Dysfunction, Left/diagnosis/*diagnostic imaging/*drug therapy/etiology ; }, abstract = {UNLABELLED: Because of the difficulty of predicting the response of patients with idiopathic dilated cardiomyopathy (IDC) to beta-blocker therapy, this study was performed to evaluate whether gated myocardial SPECT (gated SPECT) could be useful for predicting that response.

METHODS: We performed gated SPECT with (99m)Tc-sestamibi on 38 patients with IDC before treatment with a beta-blocker and standard medication. Perfusion abnormalities, left ventricular (LV) function, and spheric distortion were assessed by a quantitative software program.

RESULTS: We classified patients into 2 groups according to improvement in LV function after 4 mo of therapy. The groups consisted of 16 poor responders whose LV ejection fraction (LVEF) increased less than 10% and 22 good responders whose LVEF increased by 10% or more. The patient characteristics before therapy, including LV volume and LVEF, did not significantly differ between the 2 groups, but the size of the myocardial perfusion defect and spheric distortion were significantly greater in poor responders than in good responders.

CONCLUSION: Gated SPECT, by allowing simultaneous assessment of perfusion, function and geometry, might be useful for predicting the response of patients with IDC to beta-blocker therapy.}, } @article {pmid15059899, year = {2004}, author = {Grimshaw, MJ and Hagemann, T and Ayhan, A and Gillett, CE and Binder, C and Balkwill, FR}, title = {A role for endothelin-2 and its receptors in breast tumor cell invasion.}, journal = {Cancer research}, volume = {64}, number = {7}, pages = {2461-2468}, doi = {10.1158/0008-5472.can-03-1069}, pmid = {15059899}, issn = {0008-5472}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma in Situ/genetics/metabolism/*pathology ; Carcinoma, Ductal/genetics/metabolism/*pathology ; Cell Line, Tumor ; Chemotaxis/drug effects/physiology ; Coculture Techniques ; Endothelin-1/pharmacology/physiology ; Endothelin-2/biosynthesis/genetics/pharmacology/*physiology ; Humans ; Isoenzymes/biosynthesis ; MAP Kinase Signaling System/physiology ; Macrophages/cytology/drug effects/enzymology ; Matrix Metalloproteinases/biosynthesis ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Neoplasm Invasiveness ; RNA, Messenger/biosynthesis/genetics ; Receptor, Endothelin A/biosynthesis/genetics/*physiology ; Receptor, Endothelin B/biosynthesis/genetics/*physiology ; }, abstract = {We have studied the role of endothelins (ET-1, ET-2 and ET-3) and ET receptors (ET-RA and ET-RB) in the invasive capacity of breast tumor cells, which express ET-1 and ET-2 as well as ET-RA and ET-RB. Of five human breast tumor cell lines tested, all expressed mRNAs for ET-1, ET-2, and ET-RB. ET-RA mRNA was expressed by four of five tumor cell lines. Breast tumor cells migrated toward ET-1 and ET-2 but not toward ET-3. Chemotaxis involved signaling via both receptors, and a pertussis toxin-sensitive p42/p44 mitogen-activated protein kinase (MAPK)-mediated pathway that could be inhibited by MAPK kinase (MEK)1/2 antagonists. Chemotaxis toward ETs did not involve p38 or stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) and was not inhibited by hypoxia. Incubation of tumor cells with ET-2 also increased chemotaxis toward the chemokines CXCL12 and CCL21. As well as inducing chemotaxis of tumor cells, ET-1 and ET-2 increased tumor cell invasion through Matrigel. Furthermore, stimulation of macrophage/tumor cell cocultures with ETs led to increased matrix metalloproteinase (MMP)-2 and -9 production by macrophages and a marked increase in invasion of tumor cells. Antagonism of either ET-RA or ET-RB decreased the invasion seen in ET-stimulated cocultures, as did a broad-spectrum MMP inhibitor. Immunohistochemical staining of human breast tumor sections showed increased ET and ET receptor protein expression by tumor cells in invasive ductal carcinoma compared with normal breast tissue or ductal carcinoma in situ. Furthermore, tumor cell ET and receptor expression was stronger at the invasive margin of invasive ductal carcinomas, in the lymphovascular space, and in lymph node metastases. ET expression often colocalized with ET-RB expression in all neoplastic tissue indicating a possible autocrine action of ETs. We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells.}, } @article {pmid15053190, year = {2004}, author = {Entwistle, JW}, title = {Short- and long-term mechanical ventricular assistance towards myocardial recovery.}, journal = {The Surgical clinics of North America}, volume = {84}, number = {1}, pages = {201-221}, doi = {10.1016/S0039-6109(03)00213-5}, pmid = {15053190}, issn = {0039-6109}, mesh = {Female ; Heart Failure/diagnosis/mortality/*therapy ; Heart Function Tests ; *Heart-Assist Devices ; Hemodynamics/*physiology ; Humans ; Male ; Myocardial Contraction/physiology ; Prognosis ; Recovery of Function ; Risk Assessment ; Severity of Illness Index ; Stroke Volume ; Survival Rate ; Treatment Outcome ; Ventricular Dysfunction, Left/diagnosis/mortality/*therapy ; }, abstract = {Long-term LVADs are primarily used as a bridge to transplantation because cardiac transplantation currently offers a better long-term outlook for most patients. Some patients will not get the opportunity for transplantation due to organ shortages and long waiting lists, however, and alternate care strategies must be considered. LVAD weaning and explantation may be an appropriate course of action for patients who have IDC and in whom transplantation is not the optimal therapy. The data demonstrate that LVAD weaning may be performed successfully in selected patients with IDC, and that transplantation may be delayed or avoided altogether; however, VAD weaning is not without its risks. Many of the patients have demonstrated recurrence of heart failure at various times after undergoing device removal. Through proper monitoring, most of these patients can be identified early enough to be relisted for transplantation, although some will require reinsertion of an LVAD while waiting. The critical steps in establishing a successful VAD weaning program are proper patient selection, ventricular unloading in the early stages, the institution of heart failure medications, frequent monitoring for ventricular recovery, and a period of ventricular retraining before explantation. In addition, the surgeons must be able to perform the explantation procedure with a low operative mortality. As experience with LVAD weaning and explantation grows, we may be able to better predict which patients may be successfully treated without resorting to transplantation. Explantation may eliminate, or safely delay, the need for cardiac transplantation. Although it is unlikely that these patients will be studied in a randomized fashion, the collection of accurate and complete data may allow us to establish a database that can answer many of today's questions.}, } @article {pmid15050489, year = {2004}, author = {Molhoek, SG and Bax, JJ and van Erven, L and Bootsma, M and Boersma, E and Steendijk, P and van der Wall, EE and Schalij, MJ}, title = {Comparison of benefits from cardiac resynchronization therapy in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {93}, number = {7}, pages = {860-863}, doi = {10.1016/j.amjcard.2003.12.024}, pmid = {15050489}, issn = {0002-9149}, mesh = {Aged ; Cardiac Output/*physiology ; *Cardiac Pacing, Artificial ; Cardiomyopathy, Dilated/*mortality/physiopathology/*therapy ; Exercise Tolerance/physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/*mortality/physiopathology/*therapy ; Patient Selection ; Quality of Life ; Survival Rate ; Treatment Outcome ; }, abstract = {Cardiac resynchronization therapy (CRT) is a recently introduced therapeutic option for patients with severe heart failure and intraventricular conduction disturbances. However, it is estimated that 20% to 30% of patients may not respond to CRT. Patients with ischemic cardiomyopathy (IC) may respond less favorably to CRT compared with patients with idiopathic dilated cardiomyopathy (IDC). Accordingly, the beneficial effects of CRT were evaluated in 2 subsets of patients (IC and IDC). Seventy-four patients with end-stage heart failure, New York Heart Association (NYHA) class III or IV, left ventricular (LV) ejection fraction <35%, QRS >120ms, and left bundle branch block received a biventricular pacemaker. At baseline and 6 months after implantation these parameters were evaluated: NYHA class, Minnesota quality-of-life score, QRS duration, and 6-minute walking distance. LV ejection fraction and severity of mitral regurgitation were assessed before and 6 months after CRT using 2-dimensional echocardiography. Long-term follow-up and hospitalization rates were obtained up to 2 years. Of the 74 patients, 46% (n = 34) had IC and 54% (n = 40) IDC. At 6 months follow-up all clinical parameters, QRS duration, LV ejection fraction, and mitral regurgitation improved significantly in both groups. Long-term (2-year) follow-up showed a survival rate of 87.5% for patients with IDC and 88.3% for patients with IC. The percentages of responders to CRT (defined as an improvement in NYHA class >or=1 grade) were comparable in both groups (65% vs 71%). Therefore, the underlying etiology of heart failure (IC vs IDC) was not related to the response to CRT.}, } @article {pmid15050488, year = {2004}, author = {Seghatol, FF and Shah, DJ and Diluzio, S and Bello, D and Johnson, MR and Cotts, WG and O'Donohue, JA and Bonow, RO and Gheorghiade, M and Rigolin, VH}, title = {Relation between contractile reserve and improvement in left ventricular function with beta-blocker therapy in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {93}, number = {7}, pages = {854-859}, doi = {10.1016/j.amjcard.2003.12.023}, pmid = {15050488}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Cardiomyopathy, Dilated/complications/drug therapy/*physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Contraction/*physiology ; Myocardial Ischemia/complications/drug therapy/*physiopathology ; Predictive Value of Tests ; Prospective Studies ; Time Factors ; Ventricular Dysfunction, Left/complications/*drug therapy/*physiopathology ; }, abstract = {Beta blockers improve left ventricular (LV) ejection fraction but patient responses are heterogenous. We investigated the role of contractile reserve (CR) in predicting beta-blocker response in ischemic and nonischemic cardiomyopathy. Resting and low-dose dobutamine echocardiograms were recorded in 32 patients with heart failure (LV ejection fraction 6 apoptotic figures and those invading >3 mm from the tumor margin had significantly higher hazard rates (HRs) for recurrence (P<0.05). In IDCs with 1 to 3 nodal metastases, >2 apoptotic figures in tumor emboli in blood vessels and >5 invaded lymph vessels were associated with significantly higher HRs for tumor recurrence and death (P<0.005). In IDCs with 4 or more nodal metastases, nodal tumors with >5 mitotic figures and >5 nodes with extranodal extension were associated with significantly higher HRs for tumor recurrence or death (P<0.05). We conclude that several histological characteristics of tumors in vessels and nodes have significant implications for the progression of IDCs.}, } @article {pmid15015575, year = {2004}, author = {Rouleau-Dubois, C and Cuny, M and Ferrieres, G and Simony-Lafontaine, J and Rouanet, P and Grenier, J and Jeanteur, P and Baldet, P and Escot, C}, title = {Spontaneous apoptosis in the intra-ductal component's stroma of breast invasive carcinoma.}, journal = {Anticancer research}, volume = {24}, number = {1}, pages = {53-57}, pmid = {15015575}, issn = {0250-7005}, mesh = {Adult ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology ; DNA Fragmentation/*physiology ; Female ; Humans ; Stromal Cells/pathology ; }, abstract = {Spontaneous apoptosis by in situ detection of DNA fragmentation (DNAf) was investigated in breast invasive ductal carcinoma (IDC) frozen samples removed from 61 untreated patients. The incidence of DNAf was low in carcinoma cells and was mainly detected in the stroma. In the stroma at a distance from carcinoma cells, DNAf was inversely related to estradiol plasma level variations (p=0.01), indicating that it probably remained under physiological hormonal regulation. In the stroma adjacent to carcinoma cells, DNAf was correlated to tumor progression parameters such as the presence of a comedo intra ductal carcinoma (DCIS) component (p=0.001) and axillary lymph node metastasis (p=0.002), suggesting that this stromal compartment more probably represented a tumoral component closely associated to epithelial tumor cells. Therefore, the detection of DNAf in the adjacent stroma of breast carcinoma could help to predict progression in non invasive tumors and also in invasive tumors in those patients without lymph node invasion.}, } @article {pmid15010880, year = {2004}, author = {Yamamoto, J and Ohshima, K and Nabeshima, K and Ikeda, S and Iwasaki, H and Kikuchi, M}, title = {Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {11}, number = {4}, pages = {825-831}, pmid = {15010880}, issn = {1021-335X}, mesh = {Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnosis/metabolism/pathology ; Carcinoma, Ductal, Breast/*diagnosis/metabolism/pathology ; Carcinoma, Neuroendocrine/*diagnosis/metabolism/pathology ; Carcinoma, Small Cell/*diagnosis/metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; }, abstract = {Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.}, } @article {pmid15010798, year = {2004}, author = {Wang, CF and Gao, EQ and He, Z and Yan, CH}, title = {A novel mixed-valence complex containing Co(II)(2)Co(III)(2) molecular squares with 4,5-imidazoledicarboxylate bridges.}, journal = {Chemical communications (Cambridge, England)}, volume = {}, number = {6}, pages = {720-721}, doi = {10.1039/b315357f}, pmid = {15010798}, issn = {1359-7345}, abstract = {A heterometallic complex, Na(2)[Co(II)(2)Co(III)(2)(IDC(3-))(4)(bipy)(4)].12H(2)O (bipy = 2,2'-bipyridine), in which mixed-valence tetranuclear squares with imidazoledicarboxylate (IDC(3-)) linkers are tethered into a unique chain through disodium units, is hydrothermally synthesized and structurally and magnetically characterized.}, } @article {pmid14997049, year = {2004}, author = {Slater, M and Danieletto, S and Pooley, M and Cheng Teh, L and Gidley-Baird, A and Barden, JA}, title = {Differentiation between cancerous and normal hyperplastic lobules in breast lesions.}, journal = {Breast cancer research and treatment}, volume = {83}, number = {1}, pages = {1-10}, doi = {10.1023/B:BREA.0000010670.85915.0f}, pmid = {14997049}, issn = {0167-6806}, mesh = {Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Fibrocystic Breast Disease/metabolism/pathology ; Humans ; Immunohistochemistry/methods ; Precancerous Conditions/*metabolism/pathology ; Predictive Value of Tests ; Receptors, Purinergic P2/*metabolism ; Receptors, Purinergic P2X7 ; }, abstract = {Determining the risk that a particular area of hyperplastic breast tissue will progress to cancer is difficult and is currently expressed only as a general risk factor within the population. Using an antibody against the apoptotic purinergic receptor P2X7, we examined 40 cases each of the following histological categories: normal, moderate, florid and atypical hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive lobular and invasive ductal carcinoma. These were previously diagnosed by H&E and supplied by clinical laboratories as tissue sections. Normal and mildly hyperplastic epithelium was devoid of the cytolytic P2X7 receptors whereas all epithelial cells in all cases of in situ or invasive lobular or ductal carcinoma labelled intensely. The lobular and ductal in situ cases labelled intracellularly while the invasive epithelial cancer cells showed intense cell surface label indicating an attempt was being made to induce apoptosis. All these receptors however are non-functional and thus unable to induce apoptosis. Approximately 10% of all hyperplastic lobules examined in the biopsied tissue, regardless of H&E classification, labelled for P2X7, which is suggestive of early metabolic cancerous change. The acini within lobules were either completely labelled with P2X7 or were completely devoid of the receptor. A potential advantage of this method lies in identifying early cancerous change in hyperplastic lobules and in establishing the true extent of cancerous spread in infiltrating lesions, thus facilitating the task of reporting clear surgical margins.}, } @article {pmid14999142, year = {2004}, author = {Buijs, JT and Cleton, AM and Smit, VT and Löwik, CW and E Papapoulos, S and Pluijm, Gv}, title = {Prognostic significance of periodic acid-Schiff-positive patterns in primary breast cancer and its lymph node metastases.}, journal = {Breast cancer research and treatment}, volume = {84}, number = {2}, pages = {117-130}, doi = {10.1023/B:BREA.0000018408.77854.d1}, pmid = {14999142}, issn = {0167-6806}, mesh = {Adenocarcinoma/mortality/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; *Periodic Acid-Schiff Reaction ; Predictive Value of Tests ; Survival Analysis ; }, abstract = {Invasive ductal carcinoma is by far the largest histological subtype of breast cancer, but clinical behavior can differ greatly. Reliable morphological markers are, therefore, of invaluable help to distinguish between patients with good and poor prognosis. Histological patterns stained with periodic acid-Schiff (PAS) were previously shown to be of prognostic significance in cutaneous and uveal melanoma. In this study, we examined the presence of different PAS-positive (PAS+) structures in 54 women with infiltrating ductal adenocarcinoma of the breast and at least one axillary lymph node metastasis but no distant metastases who were followed for at least 11 years. We found that the complexity of the thin PAS+ patterns in lymph node metastases is associated with a shorter period of disease free survival (DFS) as well as of total survival (Kaplan-Meier curves). Furthermore, the presence of PAS+ networks - the most complex thin PAS+ pattern - in lymph node metastases is one of the two independent factors associated with the occurrence of a distant metastasis (multivariate Cox model). Moreover, the presence of PAS+ networks in positive lymph nodes is the feature most strongly associated with DFS. In conclusion, the presence of PAS+ networks in lymph node metastases is a new, reliable and convenient indicator for prognosis of breast cancer patients.}, } @article {pmid14997044, year = {2004}, author = {Pokieser, W and Cassik, P and Fischer, G and Vesely, M and Ulrich, W and Peters-Engl, C}, title = {Malignant pleural and pericardial effusion in invasive breast cancer: impact of the site of the primary tumor.}, journal = {Breast cancer research and treatment}, volume = {83}, number = {2}, pages = {139-142}, doi = {10.1023/B:BREA.0000010706.24181.b6}, pmid = {14997044}, issn = {0167-6806}, mesh = {Austria/epidemiology ; Breast Neoplasms/epidemiology/*pathology ; Case-Control Studies ; Female ; Humans ; Medical Records ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pericardial Effusion/epidemiology/*pathology ; Pleural Effusion, Malignant/epidemiology/*pathology ; Retrospective Studies ; }, abstract = {BACKGROUND: Malignant effusion in invasive breast cancer, either pleural or pericardial, is associated with a poor survival rate. We investigated the role of the location of invasive breast cancer in developing malignant pleural or pericardial effusion.

METHODS: Three thousand eight hundred and fifty six women with a history of invasive breast cancer between 1960 and 1994 were analyzed in a retrospective study. Two hundred and six patients (5.34%; group A) developed malignant pleural and/or pericardial fluid as the first visible clinical sign of distant metastasis. A control group of 206 patients (group B) without malignant effusions were matched in terms of clinical and pathological characteristics. The two groups were compared in respect of the location of the primary tumor. Fifty patients in group A (n = 50; 24.2%) had tumors in the inner quadrants, 83 patients (n = 83; 40.3%) in the outer quadrants, and 13 patients (n = 13; 6.3%) in a central location. No data were available for 60 patients (n = 60; 29.1%). In group B, 12 patients (n = 12; 5.9%) had tumors in the inner quadrants, 140 patients (n = 140; 68.0%) in the outer quadrants, 14 patients (n = 14; 6.8%) had centrally located tumors, while no data were available for 40 patients (n = 40; 19.4%). Invasive ductal carcinomas (IDC) located in the inner quadrants were highly significantly associated with increased pleural or pericardial effusion as the first site of distant metastasis (p
CONCLUSION: IDC in the inner quadrants were associated with a 4-fold higher rate of malignant pleural or pericardial effusions. Further studies will have to determine whether tumor location is a criterion for more aggressive adjuvant therapy.}, } @article {pmid14989923, year = {2004}, author = {Fu, L and Ikuo, M and Fu, XY and Liu, TH and Shinichi, T}, title = {[Relationship between biologic behavior and morphologic features of invasive micropapillary carcinoma of the breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {33}, number = {1}, pages = {21-25}, pmid = {14989923}, issn = {0529-5807}, mesh = {Adult ; Aged ; Breast Neoplasms/blood supply/*pathology/ultrastructure ; Carcinoma, Papillary/blood supply/*pathology/ultrastructure ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVE: To clarify the relationship between biologic behavior and morphologic features of invasive micropapillary carcinoma (IMPC) of the breast.

METHODS: Two thousand and eighty-eight cases of clinically defined monocentric breast cancer without pre-operative biopsy (except fine needle aspiration procedure) were examined by whole mammary gland serial sectioning. The clinicopathologic and morphologic features (including microscopic and ultrastructural) of IMPC were analyzed.

RESULTS: One hundred and seventeen cases of IMPC (6.2%, 117/1 880) were diagnosed during the period of study. The incidence of lymphovascular invasion (54.7%, 58/106) and nodal metastases (76.4%, 81/106) was significantly higher in IMPC, as well as the number of metastatic node (on average 9.6) was significantly more in IMPC, as compared with that of the invasive ductal carcinoma. Microscopically, the tumor was characterized by morula-like clusters and small papillae of malignant cells floating within irregular interstitial spaces and separated by fibrous septa. Ultrastructurally, microvilli were observed on the neoplastic cell surface at the periphery of the micropapillae. There were also numerous fine intermediate filaments in the cytoplasm. Newly formed capillaries were noted in the interstitium and some tumor cells were directly in contact with endothelial cells.

CONCLUSIONS: A predominant component of IMPC in breast carcinoma is associated with a higher risk of lymphovascular invasion and nodal metastasis. The aggressive behavior of IMPC can be attributed to the proliferative activity of the tumor cells, and its associated angiogenesis.}, } @article {pmid14984725, year = {2004}, author = {Fauchier, L and Babuty, D and Melin, A and Bonnet, P and Cosnay, P and Paul Fauchier, J}, title = {Heart rate variability in severe right or left heart failure: the role of pulmonary hypertension and resistances.}, journal = {European journal of heart failure}, volume = {6}, number = {2}, pages = {181-185}, doi = {10.1016/j.ejheart.2003.09.007}, pmid = {14984725}, issn = {1388-9842}, mesh = {Adult ; Arrhythmias, Cardiac/etiology ; Cardiomyopathy, Dilated/etiology/*physiopathology ; Case-Control Studies ; Electrocardiography, Ambulatory ; Female ; Heart Rate/*physiology ; Humans ; Hypertension, Pulmonary/complications/*physiopathology ; Male ; Middle Aged ; Pulmonary Wedge Pressure/physiology ; Regression Analysis ; Stroke Volume/physiology ; }, abstract = {BACKGROUND: The decrease in heart rate variability (HRV) might be related to the hemodynamic status in heart failure. However, HRV in patients with severe isolated right heart failure has not been extensively studied.

AIMS: This study compared HRV in patients with congestive heart failure (CHF) and in patients with isolated right heart failure.

METHODS: Time and frequency domain analysis of HRV on 24-h ECG recording was assessed in 15 healthy subjects and in two groups of patients with severe heart failure awaiting heart or heart/lung transplantation. These were 15 patients with CHF due to idiopathic dilated cardiomyopathy (IDC) and 10 patients with isolated right heart failure due to primary pulmonary hypertension (PPH).

RESULTS: Measurement of HRV were significantly decreased in both groups of patients compared with the control group. Patients with IDC had higher pulmonary capillary wedge pressure than patients with PPH (P=0.04) but lower pulmonary artery pressure and lower pulmonary vascular resistance (PVR) (P<0.0001). However, all the measurements of HRV were significantly lower in patients with IDC than in patients with PPH (range 22-77%, P<0.05 to P<0.01). None of the HRV measurements correlated with filling pressure measurements.

CONCLUSIONS: The increase in pulmonary vascular resistance in heart failure is not the main causal factor behind a decrease in HRV.}, } @article {pmid14965735, year = {1999}, author = {Palazzo, FF and Patel, A and Morgan, MW}, title = {Invasive ductal carcinoma of the breast metastatic to the endometrium.}, journal = {Breast (Edinburgh, Scotland)}, volume = {8}, number = {3}, pages = {147-148}, doi = {10.1054/brst.1999.0040}, pmid = {14965735}, issn = {0960-9776}, abstract = {Two patients with breast cancer which metastasized to the endometrium are described.}, } @article {pmid14965613, year = {2001}, author = {Maxwell, AJ and Hanson, IM and Sutton, CJ and Fitzgerald, J and Pearson, JM}, title = {A study of breast cancers detected in the incident round of the UK NHS Breast Screening Programme: the importance of early detection and treatment of ductal carcinoma in situ.}, journal = {Breast (Edinburgh, Scotland)}, volume = {10}, number = {5}, pages = {392-398}, doi = {10.1054/brst.1999.0266}, pmid = {14965613}, issn = {0960-9776}, abstract = {One hundred and seventy eight cancers detected on incident round screening in the UK National Health Service Breast Screening Programme were reviewed. Critical review of the immediately preceding screening films (from 3 years previously) found abnormalities at the site of the subsequently detected cancer in 93 cases (52%). Forty-eight of these (27% of the total) had microcalcification as the sole abnormality. All of these 48 women had invasive ductal carcinoma and/or ductal carcinoma in situ (DCIS) (including four cases in which DCIS was associated with another type of primary invasive breast cancer). The finding of microcalcification on the previous mammograms at the site of a subsequently detected cancer was a strong predictor for the presence of DCIS (with or without associated invasive disease) (P<0.0001). Of the women with invasive ductal carcinoma, those with microcalcification on previous films were significantly more likely to have intermediate or high grade (grade 2 or 3) tumours than those women without microcalcification on previous films (P=0.0015). Previous films were also read blind by two independent experienced breast radiologists. Cancers were correctly identified by one or both readers in 39 cases. However, 35 of the remaining 139 cases showed microcalcification which was not detected or considered significant by the readers. If only these 139 'true negative' screens are analysed, similar associations are seen between microcalcification on previous films and subsequent finding of DCIS (P=0.03) and between microcalcification on previous films and high grade invasive ductal carcinomas (P=0.015). These findings provide support for the hypothesis that microcalcification seen on previous screening films at the site of a subsequently detected invasive ductal carcinoma represents ductal carcinoma in situ. In this series, 19 of 82 women (23%) with invasive ductal carcinoma in the 'true negative' screen group had microcalcification suggestive of DCIS on mammograms taken, on average, 3 years previously. Significant microcalcification is often overlooked using current detection criteria. Early detection and treatment of DCIS is essential in order to prevent the development of aggressive invasive disease. Revision of the NHSBSP targets for DCIS detection is recommended.}, } @article {pmid14965581, year = {2001}, author = {Chandrasekharan, S and Fasanya, C and Macneill, FA}, title = {Invasive lobular carcinoma of the male breast: do we need to think of Klinefelter's syndrome?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {10}, number = {2}, pages = {176-178}, doi = {10.1054/brst.2000.0178}, pmid = {14965581}, issn = {0960-9776}, abstract = {Cancer of the male breast is generally seen in men over 60 years of age and, as in women, the commonest histological type is invasive ductal carcinoma. Invasive lobular cancers are seen very rarely because of the absence of lobules in the male breast. Genetic abnormalities such as Klinefelter's syndrome can increase the risk of breast cancer, and it is thought that there has to be some cytoarchitectural abnormality for development of lobular cancers in men.}, } @article {pmid14965568, year = {2001}, author = {Raja, MA and Hubbard, A and Salman, AR}, title = {Interval breast cancer: is it a different type of breast cancer?.}, journal = {Breast (Edinburgh, Scotland)}, volume = {10}, number = {2}, pages = {100-108}, doi = {10.1054/brst.2000.0217}, pmid = {14965568}, issn = {0960-9776}, abstract = {We have compared tumour type, tumour size, tumour grade and axillary lymph node status in three groups of women, 230 interval breast cancers (IC) in the West Sussex Breast Screening programme and 625 screen detected (SD) cancers and 916 symptomatic (S) cancers treated at Worthing Hospital between July 1989 to April 1996. Our true interval cancer detection rates were 5.28, 11.28 and 15.3 per 10,000 screened women for the 1st, 2nd and 3rd year after screening. The proportionate incidences of true interval cancer were 29%, 61% and 82% for the 1st, 2nd and 3rd year, similar to others' programmes in UK. In our programme a large proportion (42%) of IC and more than half of the true IC presented in the 3rd year after screening. Out of 230 interval cancers, 40% (90) were unclassifiable, the remaining 60% (140) were classified as: True interval cancers (T) 54% (76), False Negative Subtle (FNS) 12% (16), Occult (O) 12% (17), and 22% (31) as False Negative (FN). Analysis of interval cancers according to their classification did not demonstrate any significant difference with respect to tumour size (chi2 5.59, df 4, P=0.22), tumour grade (chi2 5.29, df 4, P=0.25) and axillary node status (chi2 3.16, df 4, P=0.53) thus establishing interval cancers as a single group. Invasive ductal carcinoma of no specific type was the main tumour type in all three groups. Analysis of variance (ANOVA) showed significant differences in size between the groups (df 2, F=71.36, p<0.0001). Symptomatic cancers were 1.19 times the size of IC while SD were 0.83 times the size of IC. The difference in groups in terms of tumour grade was significant (Kruskal-Wallis test chi2 33.31, df 2, P<0.0001). The incidence of grade 2 tumours was similar in the three groups while a third of the IC and S were grade 3 tumours. Comparison of axillary node status showed a significant difference between the three groups (chi2 26.59, df 2, P<0.0001). When means and 75th percentiles were compared IC had the greatest number of positive nodes while SD had the smallest number of positive nodes. Interval cancers are the middle spectrum between symptomatic and screen detected breast cancers and represent small cancers (<10 mm) not detected at the time of screening and de novo cancers developing in the screening interval. The need for improving the sensitivity of current screening methods and identifying newer methods of breast cancer detection is highlighted by our study.}, } @article {pmid14764699, year = {2004}, author = {Jackson, SH and Yu, CR and Mahdi, RM and Ebong, S and Egwuagu, CE}, title = {Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {172}, number = {4}, pages = {2307-2315}, doi = {10.4049/jimmunol.172.4.2307}, pmid = {14764699}, issn = {0022-1767}, mesh = {Animals ; Carrier Proteins/genetics/metabolism/*physiology ; Cell Differentiation/genetics/immunology ; Cells, Cultured ; DNA-Binding Proteins/deficiency/genetics/*physiology ; Dendritic Cells/*cytology/*immunology/metabolism ; Drug Synergism ; Feedback, Physiological/genetics/*immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interleukin-4/pharmacology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Progenitor Cells/cytology/immunology/metabolism ; Protein Biosynthesis ; Proteins/genetics/*physiology ; Repressor Proteins/biosynthesis/genetics/metabolism/*physiology ; STAT1 Transcription Factor ; Signal Transduction/genetics/*immunology ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; Trans-Activators/deficiency/genetics/*physiology ; Transcription Factors/biosynthesis/genetics/*physiology ; Transcriptional Activation/immunology ; Up-Regulation/genetics/immunology ; }, abstract = {In this study we show that activation of STAT pathways is developmentally regulated and plays a role in dendritic cell (DC) differentiation and maturation. The STAT6 signaling pathway is constitutively activated in immature DC (iDC) and declines as iDCs differentiate into mature DCs (mDCs). However, down-regulation of this pathway during DC differentiation is accompanied by dramatic induction of suppressors of cytokine signaling 1 (SOCS1), SOCS2, SOCS3, and cytokine-induced Src homology 2-containing protein expression, suggesting that inhibition of STAT6 signaling may be required for DC maturation. In contrast, STAT1 signaling is most robust in mDCs and is not inhibited by the up-regulated SOCS proteins, indicating that STAT1 and STAT6 pathways are distinctly regulated in maturing DC. Furthermore, optimal activation of STAT1 during DC maturation requires both IL-4 and GM-CSF, suggesting that synergistic effects of both cytokines may in part provide the requisite STAT1 signaling intensity for DC maturation. Analyses of STAT1(-/-) DCs reveal a role for STAT1 in repressing CD86 expression in precursor DCs and up-regulating CD40, CD11c, and SOCS1 expression in mDCs. We further show that SOCS proteins are differentially induced by IL-4 and GM-CSF in DCs. SOCS1 is primarily induced by IL-4 through a STAT1-dependent mechanism, whereas SOCS3 is induced mainly by GM-CSF. Taken together, these results suggest that cytokine-induced maturation of DCs is under feedback regulation by SOCS proteins and that the switch from constitutive activation of the STAT6 pathway in iDCs to predominant use of STAT1 signals in mDC is mediated in part by STAT1-induced SOCS expression.}, } @article {pmid14764165, year = {2004}, author = {Steinbigler, P and Haberl, R and Steinbeck, G}, title = {T wave spectral variance for noninvasive identification of patients with idiopathic dilated cardiomyopathy prone to ventricular fibrillation even in the presence of bundle branch block or atrial fibrillation.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {27}, number = {2}, pages = {156-165}, doi = {10.1111/j.1540-8159.2004.00405.x}, pmid = {14764165}, issn = {0147-8389}, mesh = {Algorithms ; Atrial Fibrillation/*complications ; Bundle-Branch Block/*complications ; Cardiac Pacing, Artificial ; Cardiomyopathy, Dilated/*complications ; Electrocardiography, Ambulatory/*methods/statistics & numerical data ; Fourier Analysis ; Heart Arrest/etiology ; Humans ; Middle Aged ; Myocardial Contraction/physiology ; Myocardial Ischemia/complications ; Reproducibility of Results ; Retrospective Studies ; Risk Factors ; Signal Processing, Computer-Assisted ; Statistics, Nonparametric ; Ventricular Fibrillation/*diagnosis/etiology ; }, abstract = {Conventional methods using Holter ECG recordings for noninvasive risk stratification are limited in patients with idiopathic dilated cardiomyopathy (IDC) prone to ventricular fibrillation (VF) having atrial fibrillation (AF) or bundle branch block (BBB). We therefore investigated, whether spectral assessment of beat-to-beat alternations of repolarization is associated with VF in these patients. Twenty-four-hour Holter ECG recordings in 462 patients with IDC were used. The VF group comprised of 64 consecutive patients who survived cardiac arrest, the no VF group consisted of 398 consecutive patients without a history of malignant ventricular arrhythmia. One hundred patients with ischemic cardiomyopathy (ICM) served as a control group. In each patient, 1,024 consecutive T waves were aligned using cross correlation methods. Two-dimensional Fourier transform (2D FFT) used the data matrix of 1,024 consecutive 200-ms segments centered to the T wave peak. Power spectra of the 2D FFT revealed the frequency content of the T wave in the first dimension and the periodicity of this frequency content in the second dimension. The ratio between periodic frequency contents and the sum of nonperiodic and periodic frequency contents between 0.5 and 50 Hz is equal to the T wave spectral variance (TWSV) index. Thus, TWSV index = 0 would mean that all 1,024 T waves are identical and TWSV index = 1 would mean that the 1,024 T waves are totally variable. The TWSV index was significantly higher in the VF group (0.93 +/- 0.14) than in the no VF group (0.53 +/- 0.13, P < 0.01). The best cutoff between the VF and the no VF group was achieved by using a TWSV index of 0.75 (sensitivity = 89%, specificity = 78%). No significant differences were observed between patients with and without AF or with and without BBB, and between patients with IDC and ICM. Even in the presence of BBB or AF spectral assessment of T wave alternations by TWSV index using 2D FFT in Holter ECG recordings, allows the identification of patients with IDC at risk for VF.}, } @article {pmid14759716, year = {2004}, author = {Greenberg, R and Barnea, Y and Kaplan, O and Kashtan, H and Skornick, Y}, title = {Detection of cancer cells in the axillary drainage using RT-PCR after operations for breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {13}, number = {1}, pages = {49-55}, doi = {10.1016/j.breast.2003.10.006}, pmid = {14759716}, issn = {0960-9776}, mesh = {Axilla/pathology/surgery ; Biomarkers, Tumor/*biosynthesis/genetics ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Case-Control Studies ; DNA Primers ; Exudates and Transudates/chemistry ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/*biosynthesis/genetics ; Neoplastic Cells, Circulating/*metabolism ; Prognosis ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The object of this study was to examine whether MUC-1 can be detected in the axillary lymphatic drainage of patients who have undergone conservative surgery for breast cancer and to assess the correlations between the presence of MUC-1 and prognostic factors in breast cancer. Sixty-eight women with invasive ductal carcinoma of the breast underwent wide local excision and axillary lymph node dissection. Axillary drains were inserted in all these cases, and the presence of MUC-1 and beta-actin was evaluated by RT-PCR in the lymphatic fluid collected after the operation. Prognostic factors included tumour size and grade, vascular and lymphatic invasion, clearance margins of the resected specimens and status of the axillary lymph nodes. RT-PCR assays for MUC-1 in the axillary fluid were positive in 17 patients (25%). The presence of MUC-1 was associated with increased tumour size and showed a positive correlation with axillary lymph node metastases and incomplete resection of the tumour. RT-PCR can disclose cancer cells in the axillary fluid after conservative surgery for breast cancer. The presence of MUC-1 in the axillary drainage may be associated with poor prognostic features, and its detection may have implications for therapy as it suggests that re-excision should be considered.}, } @article {pmid14758886, year = {2001}, author = {Misra, AK and Mishra, A and Agrawal, G and Agarwal, A and Mishra, SK}, title = {Occult breast carcinoma: a report of four cases and review of literature.}, journal = {Indian journal of cancer}, volume = {38}, number = {1}, pages = {49-54}, pmid = {14758886}, issn = {0019-509X}, mesh = {Adult ; Aged ; Algorithms ; Axilla ; Breast Neoplasms/*diagnosis/therapy ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; }, abstract = {We report four occult carcinoma breast cases in which extensive axillary node metastases was the first manifestation. Upper outer quadrentectomy with axillary dissection was done in three patients while modified radical mastectomy was done in one. Primary tumor could be found in three patients, one had squamous cell carcinoma (SCC) & two had infiltrating duct carcinoma (IDC). However primary tumor was not detected in breast tissue of the fourth patient. Extensive lymph node metastases were found in three out of 14,15 out of 15(SCC), 24 out of 24 and 1 out of three axillary nodes respectively. Results of immunohistochemical staining for estrogen and progesterone receptors on three cases were negative. All patient received postoperative radiotherapy and chemotherapy. We have reviewed the literature and discussed the approach to diagnosis and management in female patients presenting with metastatic carcinoma in the axillary nodes with emphasis on the appropriate pre-treatment evaluation.}, } @article {pmid14752511, year = {2004}, author = {Müller, FU and Loser, K and Kleideiter, U and Neumann, J and von Wallbrunn, C and Dobner, T and Scheld, HH and Bantel, H and Engels, IH and Schulze-Osthoff, K and Schmitz, W}, title = {Transcription factor AP-2alpha triggers apoptosis in cardiac myocytes.}, journal = {Cell death and differentiation}, volume = {11}, number = {5}, pages = {485-493}, doi = {10.1038/sj.cdd.4401383}, pmid = {14752511}, issn = {1350-9047}, mesh = {Adenoviridae/genetics ; Animals ; Apoptosis/*physiology ; Cardiomyopathy, Dilated/*metabolism ; Caspases/metabolism ; Cell Nucleus/*metabolism ; Cells, Cultured ; Cloning, Molecular ; DNA-Binding Proteins/genetics/*metabolism ; Genes, bcl-2/physiology ; Humans ; Myocardium ; Myocytes, Cardiac/*metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Rats ; Transcription Factor AP-2 ; Transcription Factors/genetics/*metabolism ; }, abstract = {Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology associated with apoptosis, cardiac dilatation, progressive heart failure and increased mortality. An elevation of the transcription factor activator protein 2alpha (AP-2alpha) is involved in vertebrate embryonic development and oncogenesis. Here, we show that AP-2alpha protein is expressed in the human heart and increased in human failing myocardium with IDC. Adenovirus-mediated overexpression of human AP-2alpha triggered apoptosis and increased mRNA levels of Bcl-2 family members Bax and Bcl-x in rat cardiomyocytes. Immunohistological analysis of human myocardium revealed an increased percentage of AP-2alpha-positive nuclei in IDC and, interestingly, a colocalization of AP-2alpha-positive but not -negative cells with a caspase-cleaved fragment of poly(ADP-ribose)polymerase. We suggest AP-2alpha as a novel cardiac regulator implicated in the activation of apoptosis in IDC.}, } @article {pmid14752191, year = {2004}, author = {Chanchairujira, K and Chung, CB and Kim, JY and Papakonstantinou, O and Lee, MH and Clopton, P and Resnick, D}, title = {Intervertebral disk calcification of the spine in an elderly population: radiographic prevalence, location, and distribution and correlation with spinal degeneration.}, journal = {Radiology}, volume = {230}, number = {2}, pages = {499-503}, doi = {10.1148/radiol.2302011842}, pmid = {14752191}, issn = {0033-8419}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Calcinosis/*diagnostic imaging/epidemiology ; California ; Cross-Sectional Studies ; Female ; Humans ; Intervertebral Disc/*diagnostic imaging ; Lumbar Vertebrae/*diagnostic imaging ; Male ; Middle Aged ; Radiography ; Reference Values ; Spinal Osteophytosis/*diagnostic imaging/epidemiology ; Thoracic Vertebrae/*diagnostic imaging ; }, abstract = {PURPOSE: To determine the prevalence, distribution, and location of intervertebral disk calcification (IDC) in the thoracic and lumbar spine and the association of IDC with radiographically evident spinal degenerative changes in cadavers.

MATERIALS AND METHODS: Anterior vertebral columns comprising T1 through L5 were removed from 223 cadavers (183 men, 40 women; mean age at death, 67 years; range, 37-94 years). Approximately 5-mm-thick parasagittal sections were investigated with high-contrast radiography. The presence of IDC, osteophytes, vertebral endplate abnormalities, and vacuum phenomena was recorded, and the height of disk space was measured at 3,568 intervertebral levels. Logistic regression analysis was performed.

RESULTS: IDC was identified in 178 (80%) of the 223 cadavers. Of 3,568 disks, 459 (13%) had IDC, and 289 cases (63%) were located in the annulus fibrosus. IDC was most common in the lower thoracic spine, occurring in 275 (60%) of 459 disks. IDC occurred in 159 (87%) of 183 men and 19 (48%) of 40 women. Logistic regression analysis was adjusted for age, and results showed that the frequency of IDC was significantly higher in men in upper, middle, and lower segments of the thoracic spine (P <.05) but not in the lumbar spine (P =.09). IDC correlated with increasing age (P <.001) and disk space loss (P <.001) at all spinal levels. There was no association of IDC with vacuum phenomena or vertebral endplate abnormalities at any spinal level.

CONCLUSION: IDC is common in elderly persons, especially in the annulus fibrosus and lower thoracic spine. The prevalence of IDC increases with age and extent of disk space loss.}, } @article {pmid14747067, year = {2004}, author = {Martins, MT and Witzel, AL and Sugaya, NN and Kowalski, LP and de Araujo, VC}, title = {Dendritic cell sarcoma of the oral cavity.}, journal = {Oral oncology}, volume = {40}, number = {3}, pages = {341-347}, doi = {10.1016/j.oraloncology.2003.08.012}, pmid = {14747067}, issn = {1368-8375}, mesh = {*Alveolar Process ; Dendritic Cells/*pathology ; Female ; Humans ; Maxillary Neoplasms/*diagnosis ; Middle Aged ; Sarcoma/*diagnosis ; Tomography, X-Ray Computed ; }, abstract = {Sarcomas derived from immune accessory cells are uncommon malignancies, most of them occurring in lymph nodes while extra nodal sites are very rarely affected. Based on the immune profile, the cells that give origin to these neoplasms are currently divided in: follicular dendritic cell (FDC), interdigitating dendritic cell (IDC), indeterminate cell and Langerhans cell. A case of a dendritic cell sarcoma arising in the alveolar ridge mucosa in a 50-year-old female is reported here. The lesion presented as a nodular mass without defined borders and covered by reddish mucosa. Histologically, the tumour was composed of spindle-shaped cells with large nuclei and abundant cytoplasm, arranged in variable patterns as storiform and whorled and revealing interspersed lymphocytes. No capsule could be seen and the neoplasm extended up to the lining epithelium. Immunohistochemically, the spindle cells were positive for vimentin, S-100 protein, CD1a, factor XIIIa and focally to smooth-muscle actin, but were negative for CD21, CD35, CD23 and caldesmon--all markers of follicular dendritic cells. In conclusion, the present case has morphologic pattern of dendritic cell sarcoma and the immunophenotype is compatible with IDC cells or with intermediate dendritic cells and demonstrates the overlap of features among these entities.}, } @article {pmid14746851, year = {2004}, author = {Mathieu, MC and Rouzier, R and Llombart-Cussac, A and Sideris, L and Koscielny, S and Travagli, JP and Contesso, G and Delaloge, S and Spielmann, M}, title = {The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {40}, number = {3}, pages = {342-351}, doi = {10.1016/j.ejca.2003.08.015}, pmid = {14746851}, issn = {0959-8049}, mesh = {Adult ; Aged ; Breast Neoplasms/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/pathology/surgery ; Carcinoma, Lobular/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Mastectomy/methods ; Middle Aged ; Survival Analysis ; Treatment Failure ; }, abstract = {The aim of this study was to determine the chemosensitivity of infiltrating lobular breast carcinoma (ILC) in comparison with infiltrating ductal carcinoma (IDC). Between 1987 and 1995, 457 patients with invasive T2>3 cm-T4 breast carcinomas were treated with primary chemotherapy (CT), surgery, radiation therapy. Clinical response, the possibility of breast preservation, pathological response and survival were evaluated according to the histological type. In order to evaluate the biological differences between ILC and IDC patients and their implication with regard to tumour chemosensitivity, additional immunohistochemical stainings (oestrogen receptor (ER), Bcl2, p53, c-erbB-2 and Ki67) were performed on 129 pretherapeutical specimens. 38 (8.3%) ILC were diagnosed by core needle biopsy before CT. ILC was an independent predictor of a poor clinical response (P=0.02) and ineligibility for breast-conserving surgery after neoadjuvant chemotherapy (P=0.03). Histological and biological factors predicting a poor response to CT (histological grade, ER, Ki67 and p53 status) were more frequent in ILC than in IDC patients. After a median follow-up of 98 months (range: 3-166), the low chemosensitivity of ILC did not result in a survival disadvantage. Our results demonstrate that ILC achieved a lower response to CT than IDC because of their immunohistochemical profile. Preoperative CT did not allow a high rate of conservative treatment for ILC and therefore the use of neoadjuvant CT for ILC patients should be questioned.}, } @article {pmid14746850, year = {2004}, author = {Ferlicot, S and Vincent-Salomon, A and Médioni, J and Genin, P and Rosty, C and Sigal-Zafrani, B and Fréneaux, P and Jouve, M and Thiery, JP and Sastre-Garau, X}, title = {Wide metastatic spreading in infiltrating lobular carcinoma of the breast.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {40}, number = {3}, pages = {336-341}, doi = {10.1016/j.ejca.2003.08.007}, pmid = {14746850}, issn = {0959-8049}, mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*secondary ; Carcinoma, Lobular/genetics/*secondary ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Phenotype ; }, abstract = {The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.}, } @article {pmid14744773, year = {2004}, author = {Zhao, YG and Xiao, AZ and Park, HI and Newcomer, RG and Yan, M and Man, YG and Heffelfinger, SC and Sang, QX}, title = {Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion.}, journal = {Cancer research}, volume = {64}, number = {2}, pages = {590-598}, doi = {10.1158/0008-5472.can-03-1932}, pmid = {14744773}, issn = {0008-5472}, support = {CA78646/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*enzymology/*pathology ; Carcinoma, Ductal/*enzymology/pathology ; Enzyme Activation ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Kinetics ; Matrix Metalloproteinase Inhibitors ; Matrix Metalloproteinases/*metabolism ; Matrix Metalloproteinases, Secreted ; Neoplasm Invasiveness ; Tissue Inhibitor of Metalloproteinase-2/*pharmacology ; Tissue Inhibitor of Metalloproteinases/*pharmacology ; }, abstract = {Local disruption of the integrity of both the myoepithelial cell layer and the basement membrane is an indispensable prerequisite for the initiation of invasion and the conversion of human breast ductal carcinoma in situ (DCIS) to infiltrating ductal carcinoma (IDC). We previously reported that human endometase/matrilysin-2/matrix metalloproteinase (MMP) 26-mediated pro-gelatinase B (MMP-9) activation promoted invasion of human prostate carcinoma cells by dissolving basement membrane proteins (Y. G. Zhao et al., J. Biol. Chem., 278: 15056-15064, 2003). Here we report that tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-4 are potent inhibitors of MMP-26, with apparent K(i) values of 1.6 and 0.62 nM, respectively. TIMP-2 and TIMP-4 also inhibited the activation of pro-MMP-9 by MMP-26 in vitro. The expression levels of MMP-26, MMP-9, TIMP-2, and TIMP-4 proteins in DCIS were significantly higher than those in IDC, atypical intraductal hyperplasia, and normal breast epithelia adjacent to DCIS and IDC by immunohistochemistry and integrated morphometry analysis. Double immunofluorescence labeling and confocal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9, TIMP-2, and TIMP-4 in DCIS cells. Higher levels of MMP-26 mRNA were also detected in DCIS cells by in situ hybridization.}, } @article {pmid14744536, year = {2004}, author = {Himmelfarb, M and Klopocki, E and Grube, S and Staub, E and Klaman, I and Hinzmann, B and Kristiansen, G and Rosenthal, A and Dürst, M and Dahl, E}, title = {ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer.}, journal = {Cancer letters}, volume = {204}, number = {1}, pages = {69-77}, doi = {10.1016/j.canlet.2003.09.011}, pmid = {14744536}, issn = {0304-3835}, mesh = {Amino Acid Sequence ; Blotting, Northern ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal/genetics/metabolism/pathology ; Carrier Proteins/*genetics/metabolism ; Cloning, Molecular ; DNA, Antisense/pharmacology ; Disease Progression ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Molecular Sequence Data ; Neoplasms/genetics/metabolism/pathology ; Phylogeny ; Proteinase Inhibitory Proteins, Secretory ; RNA, Messenger/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {The inter-alpha-trypsin inhibitor (ITI) family constitutes a group of proteins built up from one light chain and a variable set of heavy chains. Originally identified as plasma protease inhibitors, recent data indicate that ITI plays a role in extracellular matrix (ECM) stabilization and in prevention of tumor metastasis. Here we describe cloning as well as phylogenetic and expression analysis of a novel member of the heavy chain gene family, ITIH5. ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. However, ITIH5 diverged early from a common ancestor of the other subfamilies. We found strong downregulation of ITIH5 expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly express ITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma. ITIH5 mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss of ITIH5 expression may be involved in breast cancer development.}, } @article {pmid14731996, year = {2000}, author = {Grabau, DA and Thorpe, SM and Knoop, A and Vach, W and Schrøder, HD and Blichert-Toft, M and Al-Suliman, NN and Graversen, HP and Rose, C}, title = {Immunohistochemical assessment of oestrogen and progesterone receptors: correlations with the DCC method and clinical outcome in primary breast cancer patients.}, journal = {Breast (Edinburgh, Scotland)}, volume = {9}, number = {4}, pages = {208-217}, doi = {10.1054/brst.2000.0171}, pmid = {14731996}, issn = {0960-9776}, abstract = {Two different methods to determine steroid receptors were analysed with respect to their ability to estimate prognosis in primary breast cancer patients. The immunohistochemical assay (IHA) was compared with the dextran-coated charcoal (DCC) method of receptor determination. A random sample of 281 patients with invasive ductal carcinoma was drawn from 841 consecutive patients with primary breast carcinoma treated at Odense University Hospital between 1 January 1980 and 31 December 1990. Receptor determination by the DCC method had been carried out previously in 164 patients for the oestrogen receptor and in 132 patients for the progesterone receptor. The former group was reassessed by IHA with the antibody ER1D5, and the latter with the antibody PgR-ICA. The median follow-up time was 8.3 years (range 2.9-12.9 years). A cutoff of zero was used for the DCC method. Immunohistochemical results were quantified by counting in systematically random sampled fields of vision and values above zero were considered to be positive. Overall agreement of positive and negative cases was 86% for the oestrogen receptor and 83% for the progesterone receptor. Although the study included a limited number of patients, receptor positive cases fared better than negative cases in all situations. Investigation of the prognostic power revealed that classification based on IHA allowed better discrimination of patients than classification based on the DCC method. The reason for this difference might be because distinction between benign and malignant tissue is possible using the IHAmethod. Thus, IHAresults appear to be more clinically relevant.}, } @article {pmid14731438, year = {1999}, author = {Pointon, KS and Cunningham, DA}, title = {Ultrasound findings in pure invasive lobular carcinoma of the breast: comparison with matched cases of invasive ductal carcinoma of the breast.}, journal = {Breast (Edinburgh, Scotland)}, volume = {8}, number = {4}, pages = {188-190}, doi = {10.1054/brst.1999.0042}, pmid = {14731438}, issn = {0960-9776}, abstract = {Pure invasive lobular carcinoma is more difficult to diagnose clinically and mammographically than other invasive breast carcinomas. Our objective was to document the ultrasound appearances of pure invasive lobular carcinoma, to determine whether there were any specific features when compared to similar cases of invasive ductal carcinoma, and to compare the sensitivity of ultrasound with mammography in the diagnosis of invasive lobular carcinoma. We report on 23 cases of invasive lobular carcinoma who were matched for age and presentation with cases of invasive ductal carcinoma. High frequency ultrasound detected lesions in 22 cases of invasive lobular carcinoma and all had features highly suggestive of malignancy. Twenty-one of 23 cases of invasive ductal carcinoma also had malignant features. At mammography, six cases of invasive lobular carcinoma were not detected. Ultrasound is as specific for identifying invasive lobular carcinoma as it is for invasive ductal carcinoma. Ultrasound was more sensitive than mammography for diagnosing invasive lobular carcinoma.}, } @article {pmid14728288, year = {2003}, author = {Barbacioru, C and Arunachalam, A and Cowden, D and Kahwash, E and Saltz, JH}, title = {Pharmacokinetic mapping of breast tumors: a new statistical analysis technique for dynamic magnetic resonance imaging.}, journal = {AMIA ... Annual Symposium proceedings. AMIA Symposium}, volume = {2003}, number = {}, pages = {783}, pmid = {14728288}, issn = {1942-597X}, mesh = {Breast Neoplasms/*diagnosis/metabolism ; Carcinoma, Ductal/diagnosis ; Carcinoma, Intraductal, Noninfiltrating/diagnosis ; Contrast Media/*pharmacokinetics ; Female ; Humans ; *Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Models, Biological ; }, abstract = {Breast cancer is the most common malignancy among women, constituting a major health problem. Different MRI techniques have been investigated in the past in order to improve the detection and diagnosis of breast tumors. One such technique is the dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE-MRI), using diffusible CM (contrast media), such as Gd-DTPA. Here we employ a two compartment CM kinetics model (blood plasma and surrounding interstitial space being the two compartments), where the exchange of contrast agent between these compartments is bidirectionally linear. In this study we use images from 29 suspected breast carcinoma patients who underwent whole breast DCE-MRI. Each of these studies has 64 coronal sections of the whole breast, taken at 6 or 7 time points (the sampling period being about 2 minutes). Subsequent histo-pathological analysis of these patients reveal: 22 intraductal carcinomas (IDC), 3 intralobular carcinomas (ILC), 2 ductal carcinomas in-situ (DCIS) and 3 benign tumors.}, } @article {pmid14720138, year = {2004}, author = {De la Cruz, C and Moriya, T and Endoh, M and Watanabe, M and Takeyama, J and Yang, M and Oguma, M and Sakamoto, K and Suzuki, T and Hirakawa, H and Orita, Y and Ohuchi, N and Sasano, H}, title = {Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study.}, journal = {Pathology international}, volume = {54}, number = {2}, pages = {90-96}, doi = {10.1111/j.1440-1827.2004.01590.x}, pmid = {14720138}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply/chemistry/*pathology ; Carcinoma, Ductal, Breast/blood supply/chemistry/*secondary ; Carcinoma, Papillary/blood supply/chemistry/*secondary ; Cell Nucleus/pathology ; Female ; Fluorescent Antibody Technique, Direct ; Humans ; Lymph Nodes/pathology ; Neoplasm Invasiveness ; }, abstract = {Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent (P < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor (P < 0.05, P < 0.01), a higher frequency of HER-2 overexpression (P < 0.025), and more frequent lymph node metastases (P < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains (P < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.}, } @article {pmid14718145, year = {2004}, author = {Cordero, JM and Bernet, L and Cano, R and Bustamante, M and Vila, R and Ballester, B and González, PJ}, title = {[Study of the sentinel node in breast cancer using lymphoscintigraphy and a fast method for cytokeratin].}, journal = {Revista espanola de medicina nuclear}, volume = {23}, number = {1}, pages = {9-14}, doi = {10.1016/s0212-6982(04)72239-9}, pmid = {14718145}, issn = {0212-6982}, mesh = {Breast Neoplasms/*diagnostic imaging/*pathology ; Female ; *Frozen Sections ; Humans ; Keratins ; Lymph Nodes/*diagnostic imaging ; Radionuclide Imaging ; Sentinel Lymph Node Biopsy ; }, abstract = {INTRODUCTION: Histopathological examination of the axillary sentinel node (SN) is becoming a routine procedure in the surgical phase of infiltrating ductal carcinoma of the breast (IDC). The SN exam may yield false negative cases mainly due to identification failure of the SN but some of the false negative cases may be the result of the pathological examination procedure applied.

MATERIAL AND METHODS: Sixty two (62) cases of clinically staged N0 IDC of the breast by TNM nomenclature were assigned to breast surgery along with conventional axillary node dissection. The identification technique included lymphoscintigraphy and intraoperative gamma-detecting probe after peritumoral injection of 99mTc-labeled colloids.The histological study of SN was performed with paired 4 microm slices and staining with hematoxylin-eosin and with a fast method of cytokeratins for freezing.

RESULTS: In only two of the 62 patients, it was not possible to identify the SN. Eighteen of the remaining 60 had SN involvement by metastasis, having no metastases in the other nodes of the axillary dissection in 6 of them. Ten of those were micrometastasis (size of metastasis= or <0.2 cm). In two out of these last 10 cases, diagnosis of the micrometastasis was only possible using slices stained with CK. There were no false negative results.

CONCLUSIONS: The lymphoscintigraphy, after peritumoral injection of small volumes and low dose of the tracer, makes it possible to obtain excellent results in the intraoperative detection of the SN in breast cancer. The study of this SN with a fast method for CK decreases the number of false negative results of the technique.}, } @article {pmid14717755, year = {2004}, author = {Son, BH and Ahn, SH and Ko, CD and Ka, IW and Gong, GY and Kim, JC}, title = {Significance of mismatch repair protein expression in the chemotherapeutic response of sporadic invasive ductal carcinoma of the breast.}, journal = {The breast journal}, volume = {10}, number = {1}, pages = {20-26}, doi = {10.1111/j.1524-4741.2004.09609.x}, pmid = {14717755}, issn = {1075-122X}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*drug therapy/genetics/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/genetics/*metabolism/pathology ; Carrier Proteins ; Cisplatin/administration & dosage ; Cyclophosphamide/administration & dosage ; *DNA-Binding Proteins ; Doxorubicin/administration & dosage ; Drug Resistance, Neoplasm ; Female ; Fluorouracil/administration & dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Methotrexate/administration & dosage ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins/*metabolism ; Neoplasm Staging ; Nuclear Proteins ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Prognosis ; Proteins/*metabolism ; *Proto-Oncogene Proteins ; }, abstract = {The mismatch repair (MMR) gene plays a key role in the correction of DNA damage, and the loss of MMR has been implicated in resistance to a variety of chemotherapeutic drugs. The purpose of this study was to assess whether the reduced expression of hMLH1 and/or hMSH2 affects the chemotherapeutic responsiveness of sporadic invasive ductal carcinoma of the breast. Immunohistochemical studies were performed on 71 histologic specimens of breast cancer taken from the patients treated with surgery and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) chemotherapy for stage II or III primary breast cancer. Single-strand conformational polymorphism polymerase chain reaction (PCR-SSCP) and sequencing were carried out in 16 patients. A combined immunoreactivity score (hMLH1-IS and hMSH2-IS) was calculated by multiplying the staining grade by the intensity score. Positive expression (>4) of hMLH1-IS and hMSH2-IS were 57.7% and 60.6%, respectively, and complete losses of hMLH1 and hMSH2 were observed in 4.2% of patients. Of the patients with advanced cancer with lymph node metastasis, those having a low hMLH1-IS had a significantly higher failure rate with the CMF regimen than those having a high hMLH1-IS (p = 0.03). No significant difference was noted in chemotherapeutic response according to hMLH1 and hMSH2 expression in the CAF group. Both hMLH1-IS (p = 0.03) and progesterone receptor (PR) status (p = 0.03) were well correlated with CMF chemotherapy response in breast cancers with lymph node metastasis. Our study shows that a lack of hMLH1 expression may play a role in drug resistance, especially in the CMF group, and immunohistochemical assay for MMR protein can be used as a convenient tool for evaluating chemotherapeutic response in patients with breast cancer.}, } @article {pmid14717664, year = {2004}, author = {Zekioglu, O and Erhan, Y and Ciris, M and Bayramoglu, H and Ozdemir, N}, title = {Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma.}, journal = {Histopathology}, volume = {44}, number = {1}, pages = {18-23}, doi = {10.1111/j.1365-2559.2004.01757.x}, pmid = {14717664}, issn = {0309-0167}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*secondary/surgery ; Carcinoma, Papillary/chemistry/*secondary/surgery ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {AIMS: Invasive micropapillary carcinoma of the breast is an aggressive and distinctive variant of breast cancer. These tumours have a characteristic histological appearance and have been associated with a high incidence of axillary lymph node metastases and a poor clinical outcome. The aims of this study were to investigate the immunohistochemical profile of invasive micropapillary carcinoma of the breast, to compare it with invasive ductal carcinoma, and to identify the morphological parameters which predict its poor outcome.

METHODS AND RESULTS: Fifty-three (2.6%) invasive micropapillary carcinomas of the breast from 2022 cases of infiltrating breast carcinomas were identified by retrospective review. The patient age at presentation ranged from 33 to 78 years (mean 52.5 years). The tumour size ranged from 5 to 70 mm (mean 27 mm). Eighty-two percent (43 of 53) were of high histological grade; 69% (33 of 48) of cases with axillary lymph node dissections had positive lymph nodes; and 75.5% (40 of 53) had lymphatic invasion: 46% (22 of 48) of cases had extranodal extension. Of lymph node-positive cases, 61% had four or more metastatic lymph nodes. Of tumours with tumour size >10 mm, 77% had positive lymph nodes. The percentages of cases positive for oestrogen receptor (ER) and progesterone receptor (PR) were 68% and 61%, respectively. These values were significantly higher than the values for invasive ductal carcinomas. p53 and c-erbB-2 were detected in 48% and 54% of cases, respectively. The mean value of Ki67 was 26%. Follow-up was available in 36 patients. Eight patients had local recurrences, nine patients had distant metastases, and 10 patients died of disease within a follow-up period of 9 years.

CONCLUSION: Lymphotropism and an unfavourable prognosis are the hallmarks of this distinct entity. Prognostic markers such as ER, PR, p53, and c-erbB-2 failed to provide new criteria to allow discrimination of these tumours from other breast cancers.}, } @article {pmid14714254, year = {2003}, author = {Hinoda, Y and Ikematsu, Y and Horinochi, M and Sato, S and Yamamoto, K and Nakano, T and Fukui, M and Suehiro, Y and Hamanaka, Y and Nishikawa, Y and Kida, H and Waki, S and Oka, M and Imai, K and Yonezawa, S}, title = {Increased expression of MUC1 in advanced pancreatic cancer.}, journal = {Journal of gastroenterology}, volume = {38}, number = {12}, pages = {1162-1166}, doi = {10.1007/s00535-003-1224-6}, pmid = {14714254}, issn = {0944-1174}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/*metabolism/mortality/*pathology ; Epitope Mapping ; Female ; Humans ; Male ; Middle Aged ; Mucin-1/*metabolism ; Neoplasm Staging ; Pancreatic Neoplasms/*metabolism/mortality/*pathology ; Survival Rate ; }, abstract = {BACKGROUND: MUC1 is associated with tumor invasion and metastasis, and is expressed in pancreatic cancer with a high frequency. This study explored whether MUC1 expression affected the survival of patients with pancreatic cancer.

METHODS: Tissue specimens obtained from 70 patients with invasive ductal carcinoma of the pancreas, in pTNM stage III or IV, were immunostained with the anti-MUC1 monoclonal antibody DF3. The results of immunostaining were determined to be positive when more than 50% of the total cancer cells were positively stained. Association of the expression of the DF3 epitope with clinicopathological parameters or patients' survival was statistically evaluated.

RESULTS: The incidence of positivity of MUC1 expression was 55.7% (39/70) and this incidence was significantly higher in pTNM stage IV than in stage III (odds ratio [OR], 4.015; 95% confidence interval [CI], 1.459-11.0541; P = 0.0076). As there was a clear difference in overall survival between pTNM stages III and IV (P = 0.0016), the effect of MUC1 expression on survival was separately evaluated in each stage. It was shown that the expression of MUC1 was associated with unfavorable overall survival in stage IV (P = 0.0197).

CONCLUSIONS: Our data suggest that the expression of MUC1 may be related to the progression of pancreatic cancer.}, } @article {pmid14711979, year = {2003}, author = {Amari, M and Moriya, T and Ishida, T and Harada, Y and Ohnuki, K and Takeda, M and Sasano, H and Horii, A and Ohuchi, N}, title = {Loss of heterozygosity analyses of asynchronous lesions of ductal carcinoma in situ and invasive ductal carcinoma of the human breast.}, journal = {Japanese journal of clinical oncology}, volume = {33}, number = {11}, pages = {556-562}, doi = {10.1093/jjco/hyg109}, pmid = {14711979}, issn = {0368-2811}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Female ; Genes, Tumor Suppressor ; Humans ; *Loss of Heterozygosity ; Microsatellite Repeats ; Paraffin Embedding ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is known to possess characteristics of the pre-invasive stage of breast cancer and is the precursor to invasive ductal carcinoma (IDC). However, the natural history of the progression from DCIS to IDC remains unknown at the molecular level.

METHODS: We investigated the loss of heterozygosities (LOHs) in tumors of seven patients with a history of breast biopsy. The seven specimens were diagnosed as DCIS on histopathological re-examination. These patients were diagnosed with ipsilateral breast cancer a few years after biopsy. We used thirteen selected microsatellite markers that were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOHs in breast cancer. DNA isolated from microdissected formalin-fixed, paraffin-embedded tissues was subjected to a PCR-LOH analysis for these chromosome loci, and the pattern of LOHs was compared between the two asynchronous lesions for the seven cases.

RESULTS: In all patients except one, the LOHs were concordant at 91% as the informative chromosome loci in cases 1 to 6 were 56, and the concordance in LOH pattern between DCIS and IDC was detected at 50 loci. The LOHs had accumulated in accordance with the tumor progression from DCIS to IDC. The recurrent lesion occurred at or near the site of the primary biopsy and had similar or identical histopathologic features.

CONCLUSIONS: These recurrences observed were probably residual disease rather than true recurrences. Our results suggest the following: (i) genetic alternations accumulate during cancer progression from DCIS to IDC, (ii) DCIS is a lesion that has a high risk of developing invasive transformation and (iii) after approximately 5 years without treatment, DCIS may develop into IDC.}, } @article {pmid14710238, year = {2004}, author = {Adamina, M and Bolli, M and Albo, F and Cavazza, A and Zajac, P and Padovan, E and Schumacher, R and Reschner, A and Feder, C and Marti, WR and Oertli, D and Heberer, M and Spagnoli, GC}, title = {Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.}, journal = {British journal of cancer}, volume = {90}, number = {1}, pages = {263-269}, pmid = {14710238}, issn = {0007-0920}, mesh = {Antigens, Neoplasm/*immunology ; Epitopes ; Humans ; Immunotherapy/methods ; Liposomes ; Lymphocytes, Tumor-Infiltrating/immunology ; MART-1 Antigen ; Melanoma/*immunology ; Neoplasm Proteins/*immunology ; Skin Neoplasms/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (
METHODS AND RESULTS: Thirty-five patients with IDC and 10 age-matched healthy control subjects were enrolled. Using MCE, background-subtracted and peak myocardial contrast intensity (calibrated PMCI) were calculated as measures of myocardial blood volume. LV ejection fraction (LVEF) was calculated using the modified Simpson method. Patients with IDC were stratified into 2 groups according to the median value of the calibrated PMCI [high value group (n=17): calibrated PMCI > or = -22.7 dB, low value group (n=18): calibrated PMCI < -22.7 dB]. The calibrated PMCI was markedly reduced in patients with IDC compared with the control subjects (p=0.0025) and closely related to LVEF (r=0.688, p<0.0001). In the multivariate model, calibrated PMCI was the independent variable that predicted cardiac events in patients with IDC. According to the Kaplan-Meier analysis, cardiac event-free rates were significantly lower in the low-value group than in the high-value group (p<0.01).

CONCLUSIONS: Myocardial blood volume is closely related to LV dysfunction and future cardiac events in patients with IDC.}, } @article {pmid14693746, year = {2003}, author = {Hoque, A and Carter, J and Xia, W and Hung, MC and Sahin, AA and Sen, S and Lippman, SM}, title = {Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ to invasive ductal carcinoma of the breast.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {12}, number = {12}, pages = {1518-1522}, pmid = {14693746}, issn = {1055-9965}, support = {N01-CN-65004/CN/NCI NIH HHS/United States ; R01 CA 61979/CA/NCI NIH HHS/United States ; R01 CA 89716/CA/NCI NIH HHS/United States ; }, mesh = {Aneuploidy ; Aurora Kinase A ; Aurora Kinases ; Biomarkers, Tumor/analysis ; Biopsy, Needle ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Transformation, Neoplastic/*pathology ; Culture Techniques ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasm Invasiveness/*pathology ; Protein Serine-Threonine Kinases/*genetics ; Sampling Studies ; Sensitivity and Specificity ; }, abstract = {The biological mechanisms involved in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer are not fully understood. We previously have shown that the putative oncogene Aurora-A/STK15/BTAK, encoding a centrosome-associated kinase that regulates centrosomes and chromosome segregation, is amplified in human breast cancer. In this study, 37 archival breast tissue specimens of histologically confirmed DCIS lesions with adjacent invasive carcinoma and morphologically nonmalignant mammary ducts were analyzed immunohistochemically for expression of STK15. Statistically significant differences in overexpression of STK15 was found between invasive cancer and either nonmalignant mammary ducts (P < 0.0001) or DCIS lesions (P < 0.0005). Abnormalities in centrosome size and number was detected in the samples analyzed and 56% (14 of 25) of the cases also showed aneuploidy reflected in >2 signals of chromosome 3 and 17. Our data demonstrate that STK15 overexpression correlates with centrosome anomaly and aneuploidy in DCIS, and loss of STK15 overexpression is associated with progression of in situ to ductal invasive breast carcinoma.}, } @article {pmid14692838, year = {2004}, author = {Susnik, B and Jordi Rowe, J and Redlich, PN and Chitambar, C and Chang, CC and Kampalath, B}, title = {A unique collision tumor in breast: invasive ductal carcinoma and mucosa-associated lymphoid tissue lymphoma.}, journal = {Archives of pathology & laboratory medicine}, volume = {128}, number = {1}, pages = {99-101}, doi = {10.5858/2004-128-99-AUCTIB}, pmid = {14692838}, issn = {1543-2165}, mesh = {Aged ; Breast Neoplasms/complications/*pathology ; Carcinoma, Ductal, Breast/complications/*pathology ; Female ; Humans ; Lymphoma, B-Cell, Marginal Zone/complications/*pathology ; }, abstract = {We report an extraordinary case of a collision tumor consisting of invasive ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in the breast. A 79-year-old woman presented with a breast mass. A core biopsy performed at an outside hospital was interpreted as medullary carcinoma. On review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and axillary dissection. The excised specimen revealed a 2.1-cm, moderately differentiated invasive ductal carcinoma, partially surrounded by malignant lymphoma with areas where both tumors were intermixed. All 27 axillary lymph nodes were extensively involved by lymphoma, and 1 lymph node demonstrated metastatic carcinoma. The morphology and results of immunohistochemistry, flow cytometry, and cytogenetic analysis were consistent with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.}, } @article {pmid14691916, year = {2003}, author = {Diallo, R and Schaefer, KL and Bankfalvi, A and Decker, T and Ruhnke, M and Wülfing, P and Jackisch, C and Luttges, J and Sorensen, PH and Singh, M and Poremba, C}, title = {Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry.}, journal = {Human pathology}, volume = {34}, number = {12}, pages = {1299-1305}, doi = {10.1016/s0046-8177(03)00423-4}, pmid = {14691916}, issn = {0046-8177}, mesh = {Adult ; Aged ; Breast Neoplasms/*classification/genetics/*pathology ; Carcinoma, Ductal/genetics/*pathology ; Chromosome Aberrations ; DNA, Neoplasm/*analysis ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH). IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected, including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR. The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1 with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization analysis of the latter case showed no evidence of HER-2/neu-gene amplification. Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have immunohistochemical and genetic features that distinguish them from IDCs of the usual type.}, } @article {pmid14689308, year = {2004}, author = {Lotze, U and Egerer, R and Tresselt, C and Glück, B and Dannberg, G and Stelzner, A and Figulla, HR}, title = {Frequent detection of parvovirus B19 genome in the myocardium of adult patients with idiopathic dilated cardiomyopathy.}, journal = {Medical microbiology and immunology}, volume = {193}, number = {2-3}, pages = {75-82}, pmid = {14689308}, issn = {0300-8584}, mesh = {Adenoviridae/isolation & purification ; Adult ; Aged ; Base Sequence ; Biopsy ; Cardiomyopathy, Dilated/*virology ; Endocardium/*virology ; Enterovirus/isolation & purification ; Enterovirus Infections/virology ; Female ; *Genome, Viral ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Parvoviridae Infections/*virology ; Parvovirus B19, Human/*isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Aside from enteroviruses and other viruses, e.g., adenoviruses, which are known to be associated with idiopathic dilated cardiomyopathy (IDC), a cardiac tropism is also attributed to parvovirus B19 (PVB19). The purpose of the present study was to determine the prevalence of enterovirus, adenovirus and PVB19 genomes in the myocardium of adult patients with IDC and to analyze the significance of PVB19 with regard to the course of the disease, as compared to the other cardiotropic viruses. In 52 adult patients with IDC and 10 control patients with normal left ventricular ejection fraction (> or =55%) undergoing coronary artery bypass surgery, myocardial tissue samples were investigated for enteroviral RNA using polymerase chain reaction (PCR) and Southern blot hybridization of the PCR product. Specific nested PCR was used to assess the prevalence of adenovirus and PVB19 DNA, in addition to sequencing of the latter. The clinical and echocardiographic course of the disease was followed for a mean (+/- SD) period of 21.1+/-9.5 months. Fourteen of the 52 patients (27%) were enterovirus-positive, 2/52 (4%) patients were adenovirus-positive, 14/52 (27%) patients were PVB19-positive, 8/52 (15%) patients were enterovirus plus PVB19-positive, and in 14/52 (27%) patients no viral genomes were found. Six patients died during the follow-up period, without any significant difference between the patient groups: 1/14 (7%) in the enterovirus-positive, 0/2 (0%) in the adenovirus-positive, 2/14 (14%) in the PVB19-positive, 1/8 (12.5%) in the enterovirus plus PVB19-positive, and 2/14 (14%) in the virus-negative group. PVB19 genome was found in 4 of the 10 (40%) control patients, but no enterovirus or adenovirus genomes were detected in these patients. In conclusion, in the myocardium of patients with IDC, PVB19 is detectable as frequently as enteroviral genome. PVB19-positive patients with IDC have a rather favorable prognosis and do not differ significantly from the other virus-positive or virus-negative patient groups with respect to survival. Finally, the pathogenetic and prognostic significance of PVB19 in IDC still remains unclear.}, } @article {pmid14689049, year = {2004}, author = {Ribeiro-Silva, A and Ramalho, LN and Garcia, SB and Zucoloto, S}, title = {Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies?.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {37}, number = {1}, pages = {89-95}, doi = {10.1590/s0100-879x2004000100013}, pmid = {14689049}, issn = {0100-879X}, mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/metabolism/*virology ; Carcinoma, Ductal, Breast/genetics/metabolism/virology ; DNA-Binding Proteins ; Epstein-Barr Virus Nuclear Antigens/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Herpesvirus 4, Human/*isolation & purification ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphoproteins/*genetics ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Trans-Activators/*genetics ; Transcription Factors ; Tumor Suppressor Protein p53/*genetics ; Tumor Suppressor Proteins ; }, abstract = {Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N=12), grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8), lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1 and p53 (P=0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.}, } @article {pmid14687583, year = {2004}, author = {Nagorsen, D and Marincola, FM and Panelli, MC}, title = {Cytokine and chemokine expression profiles of maturing dendritic cells using multiprotein platform arrays.}, journal = {Cytokine}, volume = {25}, number = {1}, pages = {31-35}, doi = {10.1016/j.cyto.2003.08.012}, pmid = {14687583}, issn = {1043-4666}, mesh = {Antigens, CD ; B7-1 Antigen/metabolism ; CD40 Ligand/pharmacology ; Cells, Cultured ; Chemokine CCL22 ; Chemokine CCL5/metabolism ; Chemokines/*metabolism ; Chemokines, CC/metabolism ; Cytokines/*metabolism ; Dendritic Cells/drug effects/*physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Immunoglobulins/metabolism ; Interleukin-2/metabolism ; Interleukin-4/metabolism ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/metabolism ; Protein Array Analysis/*methods ; }, abstract = {Understanding the whole process of dendritic cell (DC) activation might help in the development of more efficient immunotherapeutic strategies for tumor patients. Part of this process is cytokine secretion, which has important effects on innate and adaptive immune response. Here, we cultured circulating monocytes for five days with interleukin-4 and GM-CSF followed by two-day culture with or without CD40 ligand and LPS to create a mature DC (mDC) and an immature DC (iDC) phenotype, respectively, characterized by differential expression of co-stimulatory molecules (CD80, CD83). We then compared the cytokine expression profile of the mDC and iDC using two protein platform arrays. Twelve supernatants from mDC paired with 12 from iDC were compared. The mDC protein expression profile showed significant increases in 16 out of 34 factors tested, including TNFalpha, IL-10, IL-12, IFNgamma, MIP1alpha, MIP1beta, IL-8, MDC, RANTES, and IL-6, which play a crucial role in the regulation of the innate immune response as well as the recruitment and activation of adaptive immune effectors. Interestingly, some of the cytokines expressed during maturation were also found in the gene expression profile identified in tumor metastases following IL-2 therapy using cDNA arrays. This finding suggests a possible role for resident DC maturation as a mediator of systemic IL-2 effects. Most important, the array of cytokines secreted during DC maturation may be considered an important component during adoptive transfer. Further characterization of the kinetics and persistence of their secretion should be undertaken in the future.}, } @article {pmid14680497, year = {2004}, author = {Yamashita, H and Nishio, M and Toyama, T and Sugiura, H and Zhang, Z and Kobayashi, S and Iwase, H}, title = {Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.}, journal = {Breast cancer research : BCR}, volume = {6}, number = {1}, pages = {R24-30}, pmid = {14680497}, issn = {1465-542X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Chi-Square Distribution ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/*biosynthesis ; Survival Analysis ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {INTRODUCTION: Many laboratories are currently evaluating the usefulness of determination of HER2, p53, and Ki67 proliferation indices using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might indeed be helpful in making treatment decisions in cancer patients, their clinical usefulness is still controversial.

METHODS: Expression of HER2, p53, and Ki67 was examined by immunohistochemistry in samples of breast tissue from 506 patients with invasive ductal carcinoma, obtained between 1981 and 1999 (median follow up period 82 months), and their significance for prognosis was analyzed.

RESULTS: Of the 506 carcinoma tissue samples, 20.1%, 29.0%, and 53.6% were positive for HER2 over-expression, p53 protein accumulation, and Ki67 expression, respectively. Over-expression of HER2 significantly reduced disease free (P = 0.02) and overall survival (P = 0.005). Accumulation of p53 protein significantly decreased disease free (P = 0.01) and overall survival (P = 0.01). Patients with tumors that were positive for both HER2 and p53 relapsed and died within a significantly shorter period of time after surgery (P = 0.0001 and P < 0.0001, respectively). In multivariate analysis, patients with both HER2 and p53 positive tumors had considerably decreased overall survival (P = 0.04), as did patients with larger tumor size and positive lymph node status.

CONCLUSION: The findings of the present study indicate that the coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.}, } @article {pmid14674989, year = {2004}, author = {Chung, MJ and Jung, SH and Lee, BJ and Kang, MJ and Lee, DG}, title = {Inactivation of the PTEN gene protein product is associated with the invasiveness and metastasis, but not angiogenesis, of breast cancer.}, journal = {Pathology international}, volume = {54}, number = {1}, pages = {10-15}, doi = {10.1111/j.1440-1827.2004.01576.x}, pmid = {14674989}, issn = {1440-1827}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/blood supply/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/blood supply/*genetics/metabolism/secondary ; Cell Nucleus/metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; *Gene Silencing ; Humans ; Immunoenzyme Techniques ; Microcirculation/metabolism/pathology ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/pathology ; Neoplasm Recurrence, Local ; *Neovascularization, Pathologic ; PTEN Phosphohydrolase/*genetics/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {PTEN is a novel tumor-suppressor gene located on chromosomal band 10q23. Loss of PTEN function has been implicated in the progression of several types of cancer, but the correlation between loss of PTEN expression and advanced carcinomas is not well established. The capacity for angiogenesis of a tumor is known to play a very important role in growth and metastasis, and there have been reports that PTEN relates to angiogenesis. In the present study, formalin-fixed and paraffin embedded tissues from 101 patients with breast carcinomas, including 88 cases of invasive ductal carcinomas and 13 cases of ductal carcinoma in situ (DCIS), were evaluated by immunohistochemical methods for the expression of PTEN and vascular endothelial growth factor (VEGF), as well as microvessel density (MVD). The results were compared with the clinicopathologic parameters. There was no loss of PTEN expression in any of the cases of DCIS, but 28 (32%) of the 88 invasive cases did not express PTEN. Loss of PTEN expression was associated with lymph node metastasis (P = 0.03), but did not correlate with tumor size, tumor grade, MVD or recurrence. VEGF expression significantly correlated with lymph node metastasis in invasive ductal carcinoma (P = 0.01). There was no correlation between the expression of PTEN and that of VEGF (P = 0.63). The present study suggests that loss of PTEN expression is common and correlates with tumor progression and lymph node metastasis in breast carcinoma. The relationship between loss of PTEN and progression of breast cancer may not be explained by modulation of angiogenesis.}, } @article {pmid14663374, year = {2003}, author = {Menes, T and Schachter, J and Morgenstern, S and Fenig, E and Lurie, H and Gutman, H}, title = {Primary squamous cell carcinoma (SqCC) of the breast.}, journal = {American journal of clinical oncology}, volume = {26}, number = {6}, pages = {571-573}, doi = {10.1097/01.coc.0000045809.85995.3B}, pmid = {14663374}, issn = {1537-453X}, mesh = {Adult ; *Breast Neoplasms/diagnosis/therapy ; *Carcinoma, Squamous Cell/diagnosis/therapy ; Disease Progression ; Female ; Humans ; Middle Aged ; Prognosis ; }, abstract = {Primary squamous cell carcinoma (SqCC) of the breast is a rare tumor that presents a unique biologic behavior. Thus, it challenges the justification for routine axillary dissection and adjuvant therapy. A MEDLINE search of all reported cases of primary SqCC of the breast was performed. Data on lymph node status, estrogen receptor (ER) and progesterone receptor (PR) status, and surgical and adjuvant treatment modalities were collected. We add three cases from our own experience. SqCC has several unique biologic characteristics; it is associated with a lower rate of lymph node metastasis at presentation (22% vs. 40-60% for infiltrating ductal carcinoma [IDC]) and a significant rate of distant metastasis without lymph node involvement. ER and PR receptor levels are usually very low. Because lymph node involvement plays a lesser prognostic and therapeutic role in this disease, we propose a more selective approach (i.e., sentinel node biopsy). The issue of adjuvant treatment remains unresolved, owing to lack of data. Surgical and medical treatment of SqCC of the breast should be tailored to fit its distinct biologic characteristics. The 5-fluorouracil-doxorubicin-cisplatin combination may be warranted in lieu of the combinations used for IDC.}, } @article {pmid14652816, year = {2003}, author = {Serrero, G and Ioffe, OB}, title = {Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium.}, journal = {Human pathology}, volume = {34}, number = {11}, pages = {1148-1154}, doi = {10.1016/s0046-8177(03)00425-8}, pmid = {14652816}, issn = {0046-8177}, support = {CA 85367/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/*biosynthesis ; Ki-67 Antigen/metabolism ; Progranulins ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium. PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression. These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.}, } @article {pmid14643022, year = {2003}, author = {Kapucuoglu, N and Coban, T and Raunio, H and Pelkonen, O and Edwards, RJ and Boobis, AR and Iscan, M}, title = {Expression of CYP3A4 in human breast tumour and non-tumour tissues.}, journal = {Cancer letters}, volume = {202}, number = {1}, pages = {17-23}, doi = {10.1016/j.canlet.2003.08.015}, pmid = {14643022}, issn = {0304-3835}, mesh = {Adult ; Aged ; Breast/enzymology ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Menopause ; Middle Aged ; Receptors, Estrogen/metabolism ; Smoking ; }, abstract = {Cytochrome P450 3A4 (CYP3A4), a member of multigene superfamily of enzymes, plays a major role in the activation of procarcinogens such as polycyclic hydrocarbon dihydrodiols, aflatoxins and heterocyclic amines as well as of several drugs including tamoxifen which is used in breast cancer therapy. Using immunohistochemistry, the cellular distribution and the level of expression of CYP3A4 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP3A4 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 68% (17/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP3A4 was detected in normal epithelium and myoepithelium. Only focal staining was noted in some of the non-epithelial cells (e.g. endothelial cells) in normal breast tissues. When CYP3A4 staining was assessed semiquantitatively the mean staining score values of CYP3A4 were found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP3A4 protein is expressed in both tumour and normal breast tissue with an increased expression in tumours.}, } @article {pmid14641800, year = {2003}, author = {Laghi-Pasini, F and Guideri, F and Petersen, C and Lazzerini, PE and Sicari, R and Capecchi, PL and Picano, E}, title = {Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients.}, journal = {Journal of internal medicine}, volume = {254}, number = {6}, pages = {591-596}, doi = {10.1111/j.1365-2796.2003.01234.x}, pmid = {14641800}, issn = {0954-6820}, mesh = {Adenosine/*blood ; Aged ; Cardiomyopathy, Dilated/*blood/diagnostic imaging ; Case-Control Studies ; Dipyridamole ; Echocardiography, Stress/methods ; Female ; Hemodynamics/drug effects ; Humans ; Male ; Middle Aged ; Vasodilator Agents ; }, abstract = {BACKGROUND: Heart failure is characterized by chronically increased adenosine levels, which are thought to express a protective anti-heart failure activation of the adenosinergic system. The aim of the study was to assess whether the activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can be mirrored by a blunted increase in plasma adenosine concentration following dipyridamole stress, which accumulates endogenous adenosine.

METHODS: Two groups were studied: IDC patients (n = 19, seven women, mean age 60 +/- 12 years) with angiographically confirmed normal coronary arteries and left ventricular ejection fraction <35%; and normal controls (n = 15, six women, mean age 68 +/- 5 years). Plasma adenosine was assessed by high-performance liquid chromatography methods in blood samples from peripheral vein at baseline and 12 min after dipyridamole infusion (0.84 mg kg-1 in 10 min).

RESULTS: At baseline, IDC patients showed higher plasma adenosine levels than controls (276 +/- 27 nM L-1 vs. 208 +/- 48 nM L-1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma adenosine levels than controls (322 +/- 56 nM L-1 vs. 732 +/- 250 nM L-1, P < 0.001). The dipyridamole-induced percentage increase in plasma adenosine over baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine levels found in normal subjects.

CONCLUSION: Patients with IDC have abnormally high baseline adenosine levels and--even more strikingly--blunted plasma adenosine increase following dipyridamole infusion. This is consistent with a chronic activation of the adenosinergic system present in IDC, which can be measured noninvasively in the clinical theatre.}, } @article {pmid14640991, year = {2003}, author = {Segerlantz, M and Bramnert, M and Manhem, P and Laurila, E and Groop, LC}, title = {Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults.}, journal = {European journal of endocrinology}, volume = {149}, number = {6}, pages = {511-519}, doi = {10.1530/eje.0.1490511}, pmid = {14640991}, issn = {0804-4643}, mesh = {Adult ; Aged ; Analysis of Variance ; Blood Glucose/drug effects ; Double-Blind Method ; Energy Metabolism/drug effects ; Fatty Acids, Nonesterified/blood ; Female ; Hormone Replacement Therapy/adverse effects ; Human Growth Hormone/*deficiency/*therapeutic use ; Humans ; Hypolipidemic Agents/*pharmacology ; Insulin/*metabolism ; Lipolysis/*drug effects/physiology ; Male ; Middle Aged ; Pyrazines/*pharmacology ; }, abstract = {OBJECTIVE: Previous studies evaluating the lipolytic effect of GH have in general been performed in subjects on chronic GH therapy. In this study we assessed the lipolytic effect of GH in previously untreated patients and examined whether the negative effect of enhanced lipolysis on glucose metabolism could be counteracted by acute antilipolysis achieved with acipimox.

METHODS: Ten GH-deficient (GHD) adults participated in four experiments each, during which they received in a double-blind manner: placebo (A); GH (0.88+/-0.13 mg) (B); GH+acipimox 250 mg b.i.d. (C); and acipimox b.i.d. (no GH) (D), where GH was given the night before a 2 h euglycemic, hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry.

RESULTS: GH increased basal free fatty acid (FFA) levels by 74% (P=0.0051) and insulin levels by 93% (P=0.0051). This resulted in a non-significant decrease in insulin-stimulated glucose uptakes (16.61+/-8.03 vs 12.74+/-5.50 micromol/kg per min (s.d.), P=0.07 for A vs B). The rates of insulin-stimulated glucose uptake correlated negatively with the FFA concentrations (r=-0.638, P<0.0001). However, acipimox caused a significant improvement in insulin-stimulated glucose uptake in the GH-treated patients (17.35+/-5.65 vs 12.74+/-5.50 micromol/kg per min, P=0.012 for C vs B). The acipimox-induced enhancement of insulin-stimulated glucose uptake was mainly due to an enhanced rate of glucose oxidation (8.32+/-3.00 vs 5.88+/-2.39 micromol/kg per min, P=0.07 for C vs B). The enhanced rates of glucose oxidation induced by acipimox correlated negatively with the rate of lipid oxidation in GH-treated subjects both in basal (r=-0.867, P=0.0093) and during insulin-stimulated (r=-0.927, P=0.0054) conditions. GH did not significantly impair non-oxidative glucose metabolism (6.86+/-5.22 vs 8.67+/-6.65 micromol/kg per min, P=NS for B vs A). The fasting rate of endogenous glucose production was unaffected by GH and acipimox administration (10.99+/-1.98 vs 11.73+/-2.38 micromol/kg per min, P=NS for B vs A and 11.55+/-2.7 vs 10.99+/-1.98 micromol/kg per min, P=NS for C vs B). On the other hand, acipimox alone improved glucose uptake in the untreated GHD patients (24.14+/-8.74 vs 16.61+/-8.03 micromol/kg per min, P=0.0077 for D vs A) and this was again due to enhanced fasting (7.90+/-2.68 vs 5.16+/-2.28 micromol/kg per min, P=0.01 for D vs A) and insulin-stimulated (9.78+/-3.68 vs 7.95+/-2.64 micromol/kg per min, P=0.07 for D vs A) glucose oxidation.

CONCLUSION: The study of acute administration of GH to previously untreated GHD patients provides compelling evidence that (i) GH-induced insulin resistance is mainly due to induction of lipolysis by GH; and (ii) inhibition of lipolysis can prevent the deterioration of insulin sensitivity. The question remains whether GH replacement therapy should, at least at the beginning of therapy, be combined with means to prevent an excessive stimulation of lipolysis by GH.}, } @article {pmid14645694, year = {2003}, author = {Guerra, I and Algorta, J and Díaz de Otazu, R and Pelayo, A and Fariña, J}, title = {Immunohistochemical prognostic index for breast cancer in young women.}, journal = {Molecular pathology : MP}, volume = {56}, number = {6}, pages = {323-327}, pmid = {14645694}, issn = {1366-8714}, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Survival Rate ; Tumor Suppressor Protein p53/analysis ; }, abstract = {AIMS: Women under 35 years of age comprise a small proportion of patients with breast cancer, but determining their prognosis can be difficult. This prospective, multivariate study looked at several factors with the aim of obtaining a useful index to evaluate the prognosis of these women.

METHODS: In total, 108 patients below 35 years of age affected by invasive ductal carcinoma without distant metastasis were studied. The mean duration of the follow up period was six years. Histopathological (tumour size, histological grade, and lymph node stage) and immunohistochemical (c-erbB-2, p53, oestrogen receptor, and progesterone receptor) factors were measured in all patients, and the Nottingham prognostic index (NPI) was then calculated. An immunohistochemical prognostic index (IHPI) was created using the arithmetic sum of the four individual immunohistochemical factors.

RESULTS: In univariate assessment of survival, all the studied factors yielded a significant association with either overall survival or disease free survival, except for c-erbB-2 and p53 with disease free survival. In univariate calculation of risk, all the factors gave significant results; however, in multivariate analysis only tumour size, histological grade, and progesterone receptor were significant. Both NPI and IHPI correlated significantly with prognosis. In multivariate regression analysis, IHPI correlated with tumour size and there was a significant interaction between both variables.

CONCLUSION: IHPI is very useful in determining the prognosis of tumours < or = 2 cm and of moderate use for tumours > 2, although it has no use in tumours > 5 cm.}, } @article {pmid14635052, year = {2003}, author = {Pietra, G and Romagnani, C and Mazzarino, P and Millo, E and Moretta, L and Mingari, MC}, title = {Comparative analysis of NK- or NK-CTL-mediated lysis of immature or mature autologous dendritic cells.}, journal = {European journal of immunology}, volume = {33}, number = {12}, pages = {3427-3432}, doi = {10.1002/eji.200324515}, pmid = {14635052}, issn = {0014-2980}, mesh = {Cells, Cultured ; Cytomegalovirus/immunology ; *Cytotoxicity, Immunologic ; Dendritic Cells/*physiology ; HLA Antigens/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Killer Cells, Natural/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viral Proteins/immunology ; }, abstract = {Natural killer (NK) cells have been shown to kill efficiently autologous immature dendritic cells (iDC), while sparing those undergone maturation. In this study we investigated the effect of the interaction between autologous DC and NK-cytolytic T lymphocytes (NK-CTL), a subset of HLA-E-restricted CD8(+) T cells that express HLA class I-specific inhibitory NK receptors. Although these cells share with NK cells various phenotypic and functional features (such as the capacity to lyse most allogeneic, NK-susceptible tumor cell lines), different from NK cells, NK-CTL failed to lyse autologous DC. However, after pulsing DC with a cytomegalovirus-derived, HLA-E-binding peptide recognized by NK-CTL, both iDC and mature DC became highly susceptible to lysis. On the other hand,the addition of the peptide resulted in the down-regulation of the NK-mediated lysis of the same autologous iDC. The capability of killing autologous DC, presenting a non-self, HLA-E-binding peptide, may represent a feedback mechanism by which NK-CTL down-regulate HLA-E-restricted responses to certain pathogens.}, } @article {pmid14634509, year = {2003}, author = {Tsutsui, S and Kume, M and Era, S}, title = {Prognostic value of microvessel density in invasive ductal carcinoma of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {4}, pages = {312-319}, doi = {10.1007/BF02967651}, pmid = {14634509}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*blood supply/pathology/therapy ; Carcinoma, Ductal/*blood supply/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Microcirculation ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Recurrence ; }, abstract = {BACKGROUND: Although the prognostic value of microvessel density (MVD) has been studied in breast cancer, the results still remain controversial.

PATIENTS AND METHODS: Paraffin embedded sections of invasive ductal carcinoma of the breast were immunohistochemically stained for factor VIII- related antigen in 252 patients with a median follow-up duration of 7.0 years. MVD quantification of the three most vascular areas at a magnification of x 200 was performed.

RESULTS: The 252 patients were stratified into high and low MVD groups according to a cut-off value that was the upper one-third MVD value of all patients. The patients with a high MVD had a significantly worse outcome in terms of both disease free survival (DFS) (p< 0.0001) and overall survival (OS) (p= 0.0012) compared with those with a low MVD. The same effects were seen in patients with lymph node negative as well as positive breast cancer. Multivariate analyses indicated the nodal status, nuclear grade and MVD (p= 0.0001) to be independent prognostic factors for the DFS, while the nodal status, estrogen receptor status, tumor size and MVD (p= 0.0006) were independent prognostic factors for the OS.

CONCLUSION: MVD was found to be an independent prognostic indicator of recurrence and death for breast cancer, and is therefore considered to be a useful factor for selecting high risk patients to receive adjuvant therapies.}, } @article {pmid14634505, year = {2003}, author = {Yoo, KY and Kang, D}, title = {Current researches on breast cancer epidemiology in Korea.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {4}, pages = {289-293}, doi = {10.1007/BF02967647}, pmid = {14634505}, issn = {1340-6868}, mesh = {Biomedical Research/trends ; Breast Neoplasms/*epidemiology/*genetics/mortality ; Female ; Genetic Predisposition to Disease ; Humans ; Incidence ; Korea/epidemiology ; Mortality/trends ; *Polymorphism, Genetic ; Risk Factors ; }, abstract = {As a cause of death in women, breast cancer ranks second to stomach cancer in Korea. Age-standardized mortality rates for breast cancer steadily increased during the 1980s and 1990s. There are big differences in the incidence rates for breast cancer compared with Western countries. Epidemiological features, trends in morbidity and mortality, various age-specific incidence curves, migrant study results, and analysis of the risk factors, however, suggest that the incidence of breast cancer might be further increasing in Korea. The key epidemiological hormonal risk factors for breast cancer are all explicable in terms of the estrogen augmented by progesterone hypothesis. These include older age, family history of breast cancer, early menarche, late menopause, late full-term pregnancy, and never a breast feeding. Both the establishment of high-risk groups and the estimation of lifetime risk are essential to develop a control strategy against breast cancer. Invasive ductal carcinoma is the most common histologic type of breast cancer in Korea, and the five-year survival rate has been estimated as 80-83%. Recent studies on the identification of susceptibility factors such as genetic polymorphisms of GSTM1/T1/P1, COMT, CYP2E1, CYP19, CYP17, ER-alpha, XRCC1, XRCC3, RAD52, TGF-alpha, TNF-alpha, IL-1B, IL-1RN, CDK7 etc. that predispose individuals to breast cancer by gene-environment or gene-gene interactions may possibly give further insight into both the etiology and the prevention of this malignancy.}, } @article {pmid14627268, year = {2003}, author = {Joseph, KA and El-Tamer, M and Ditkoff, BA and Komenaka, I and Horowitz, L and Schnabel, F}, title = {A 40-year delayed locoregional recurrence of breast carcinoma following mastectomy.}, journal = {The American surgeon}, volume = {69}, number = {11}, pages = {1015-1016}, pmid = {14627268}, issn = {0003-1348}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/*surgery ; Carcinoma, Ductal, Breast/*surgery ; Female ; Humans ; *Mastectomy, Modified Radical ; *Neoplasm Recurrence, Local/diagnosis/surgery ; Time Factors ; }, abstract = {A 90-year-old woman who underwent a left modified radical mastectomy 40 years ago with no further adjuvant treatment presented with a left chest wall mass at the suture line. A biopsy of the mass confirmed that it was invasive ductal carcinoma of the breast. After a negative metastatic work-up, the patient underwent a local resection of the chest wall mass with clear margins. We present here the longest documented delayed recurrence after modified radical mastectomy reported in the literature.}, } @article {pmid14624360, year = {2004}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Prognostic significance of the intra-vessel tumor characteristics of invasive ductal carcinoma of the breast: a prospective study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {444}, number = {1}, pages = {20-27}, pmid = {14624360}, issn = {0945-6317}, mesh = {Adult ; Aged ; Analysis of Variance ; Apoptosis ; Blood Vessels/*pathology ; Breast Neoplasms/*blood supply/mortality/*pathology ; Carcinoma, Ductal, Breast/*blood supply/mortality/*pathology ; Endothelium, Lymphatic/pathology ; Endothelium, Vascular/pathology ; Female ; Humans ; Lymphatic Metastasis/pathology ; Lymphatic Vessels/*pathology ; Middle Aged ; Mitosis ; Muscle, Smooth, Vascular/pathology ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prognosis ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; Survival Rate ; }, abstract = {Invasive ductal carcinomas (IDCs) of the breast are composed of stroma-invasive tumors and tumors in vessels. The purpose of this study was to prospectively investigate whether the histological characteristics of the tumors in vessels were more significantly associated with the outcome of 393 IDC patients than well-known histological parameters. Multivariate analyses showed greater than six apoptotic figures in tumor cells in lymph vessels to be significantly associated with increased hazard rates (HRs) of tumor recurrence and death in IDC patients without nodal metastasis (P<0.05). Among IDC patients with nodal metastasis whose tumors were positive for estrogen receptors (ERs) or progesterone receptors (PRs) or both, greater than six apoptotic figures in tumor cells in lymph vessels and greater than four mitotic figures in tumor cells in lymph vessels significantly increased the HR of tumor recurrence and the HR of death, respectively (P<0.05). Among IDC patients with nodal metastases whose tumors were negative for ERs and PRs, multivariate analyses showed that greater than two apoptotic figures in the blood vessel tumor emboli significantly increased the HRs of tumor recurrence and death (P<0.005). We conclude that apoptotic figures and mitotic figures in tumor cells in vessels are very important prognostic indicators for patients with IDC of the breast.}, } @article {pmid14623812, year = {2003}, author = {Grimm, W and Christ, M and Bach, J and Müller, HH and Maisch, B}, title = {Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.}, journal = {Circulation}, volume = {108}, number = {23}, pages = {2883-2891}, doi = {10.1161/01.CIR.0000100721.52503.85}, pmid = {14623812}, issn = {1524-4539}, mesh = {Adolescent ; Adrenergic beta-Antagonists/therapeutic use ; Adult ; Aged ; Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/*epidemiology/etiology/prevention & control ; Atrial Fibrillation/complications ; Baroreflex/drug effects ; Cardiomyopathy, Dilated/*complications/drug therapy ; Death, Sudden, Cardiac/epidemiology/etiology ; Defibrillators, Implantable ; Electric Countershock ; Electrocardiography, Ambulatory ; Female ; Germany/epidemiology ; Heart Rate ; Humans ; Life Tables ; Male ; Middle Aged ; Phenylephrine ; Proportional Hazards Models ; Prospective Studies ; Risk ; Stroke Volume ; Survival Analysis ; Tachycardia, Ventricular/epidemiology/etiology ; Ventricular Fibrillation/epidemiology/etiology ; }, abstract = {BACKGROUND: Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC).

METHODS AND RESULTS: Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52+/-21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend toward higher arrhythmia risk (RR, 1.7; 95% CI, 0.9 to 3.3; P=0.11), whereas beta-blocker therapy was associated with a trend toward lower arrhythmia risk (RR, 0.6; 95% CI, 0.3 to 1.2; P=0.13). In patients with atrial fibrillation, multivariate Cox analysis also identified LV ejection fraction and absence of beta-blocker therapy as the only significant arrhythmia risk predictors.

CONCLUSIONS: Reduced LV ejection fraction and lack of beta-blocker use are important arrhythmia risk predictors in IDC, whereas signal-averaged ECG, baroreflex sensitivity, heart rate variability, and T-wave alternans do not seem to be helpful for arrhythmia risk stratification. These findings have important implications for the design of future studies evaluating prophylactic implantable cardioverter-defibrillator therapy in IDC.}, } @article {pmid14614327, year = {2003}, author = {Tisserand, P and Fouquet, C and Barrois, M and Gallou, C and Dendale, R and Stoppa-Lyonnet, D and Sastre-Garau, X and Fourquet, A and Soussi, T}, title = {Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors.}, journal = {Cancer biology & therapy}, volume = {2}, number = {5}, pages = {559-563}, doi = {10.4161/cbt.2.5.511}, pmid = {14614327}, issn = {1538-4047}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; Carcinoma, Medullary/*genetics/pathology ; Cytokines/*genetics ; *DNA Methylation ; DNA, Neoplasm/genetics/metabolism ; Female ; Genes, BRCA1/*physiology ; Genes, p53/physiology ; Genetic Predisposition to Disease ; Humans ; Mutation/genetics ; Promoter Regions, Genetic ; RNA, Neoplasm/genetics/metabolism ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Medullary carcinoma is a poorly differentiated breast cancer with a high histologic grade and a paradoxically good prognosis. It accounts for only 3 percent of all breast cancers except in BRCA-1 families, in which it can account for as many as 13 percent of cancers. To date, only histologic criteria have been used to define this tumor type. In an attempt to more clearly define the genetic pathway leading to this subtype of cancer, we recently demonstrated that nearly 100 percent of these carcinomas display p53 mutations. In the present study, we extended our analysis to include HIN-1, a candidate tumor suppressor that has been shown to be silenced by methylation in the majority of breast tumors. In striking contrast to unselected sporadic invasive ductal carcinoma, we show that medullary carcinomas do not display a high frequency of HIN-1 methylation (p less than 0.001). This feature is also found in BRCA-1 associated tumors that shared several histologic characteristics with medullary carcinomas of the breast. Medullary carcinoma of the breast should therefore be considered to be a unique entity defined by specific histologic and molecular traits.}, } @article {pmid14611905, year = {2003}, author = {Wang, Q and Zhang, M and Ding, G and Liu, Y and Sun, Y and Wang, J and Zhang, W and Fu, Z and Cao, X}, title = {Anti-ICAM-1 antibody and CTLA-4Ig synergistically enhance immature dendritic cells to induce donor-specific immune tolerance in vivo.}, journal = {Immunology letters}, volume = {90}, number = {1}, pages = {33-42}, doi = {10.1016/s0165-2478(03)00160-3}, pmid = {14611905}, issn = {0165-2478}, mesh = {Abatacept ; Animals ; Cell Differentiation ; Dendritic Cells/*immunology ; Drug Synergism ; Graft Survival ; Heart Transplantation ; *Immune Tolerance ; Immunoconjugates/*immunology ; Intercellular Adhesion Molecule-1/*immunology ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; T-Lymphocytes/*immunology ; Transplantation, Homologous ; }, abstract = {Immature dendritic cells (DC) have been demonstrated to induce T-cell hyporesponsiveness in vitro and immune tolerance in vivo. However, immature DC (iDC) may become mature once infused in vivo, thus limiting the prolongation of the allograft survival. Considering that mature DC express high level of B7, intercellular adhesion molecule-1 (ICAM-1), and T-cell activation needs costimulation signals provided by DC, we selected anti-ICAM-1 mAb and cytotoxic T lymphocyte antigen-4Ig fusion protein (CTLA-4Ig) for in vivo administration to block costimulation pathways in order to further improve the efficacy of iDC to induce immune tolerance. Seven days before allogeneic cardiac transplantations, the recipients were intravenously (i.v.) pretreated of donor-derived iDC with or without simultaneous injections of anti-ICAM-1 mAb and CTLA-4Ig. CTLA-4Ig or anti-ICAM-1 mAb administration alone resulted in significant prolongation of cardiac allograft survival induced by iDC. When used simultaneously, CTLA-4Ig and anti-ICAM-1 mAb induced permanent allografts acceptance even in 90% recipients. The recipients could keep the skin alive for a longer time in the donor-specific second transplantation, but no effect was observed on the skin from C3H third-party mice. The efficient induction of donor-specific tolerance observed above may be related to the more potent inhibition of donor-specific T-cell responses including cytotoxicity activity, Th1 cytokines production, and alloantibody production by the combined use of anti-ICAM-1 mAb and CTLA-4Ig. Our data suggest that anti-ICAM-1 antibody and CTLA-4Ig can synergistically enhance iDC to induce donor-specific immune tolerance in vivo.}, } @article {pmid14605963, year = {2003}, author = {Yamaguchi, K and Nakano, K and Kobayashi, K and Ogura, Y and Konomi, H and Sugitani, A and Tanaka, M}, title = {Appleby operation for pancreatic body-tail carcinoma: report of three cases.}, journal = {Surgery today}, volume = {33}, number = {11}, pages = {873-878}, doi = {10.1007/s00595-003-2602-7}, pmid = {14605963}, issn = {0941-1291}, mesh = {Biopsy, Needle ; Carcinoma/*pathology/*surgery ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Node Excision/methods ; Lymph Nodes/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatectomy/*methods ; Pancreatic Neoplasms/*pathology/*surgery ; Risk Assessment ; Treatment Outcome ; }, abstract = {The clinical course of patients with carcinoma of the pancreas, especially of the body-tail, remains dismal despite recent advances in diagnostic and therapeutic procedures. We present three case reports to evaluate the role of the Appleby operation in the treatment of pancreatic body-tail cancer. Care 1 was a 55-year-old Japanese woman who underwent the Appleby operation for mucinous cystadenocarcinoma of the body and tail of the pancreas invading the stomach, celiac axis, superior mesenteric and splenic arteries, and the splenic, superior mesenteric, and portal veins. Local recurrence and peritoneal dissemination with malignant ascites were found 7 months later and she died 10 months after the operation. Case 2 was a 61-year-old Japanese man who underwent the Appleby operation with 20 Gy radiation therapy for invasive ductal carcinoma of the body of the pancreas involving the celiac axis, common hepatic, splenic, and left gastric arteries, and the splenic vein. Peritoneal dissemination with malignant ascites was evident 5 months later and he died 14 months after the operation. Case 3 was a 50-year-old Japanese man who underwent the Appleby operation with 20 Gy radiation therapy for invasive ductal carcinoma of the body of the pancreas invading the stomach, splenic artery, celiac axis, and splenic vein. Multiple hepatic metastases were found 2 months later and the patient died 8 months after the operation. Based on our experience of these three cases, we conclude that the indications for the Appleby operation to treat locally advanced pancreatic body carcinoma are still limited because it does not improve quality of life or clinical outcome.}, } @article {pmid14601057, year = {2003}, author = {Fackler, MJ and McVeigh, M and Evron, E and Garrett, E and Mehrotra, J and Polyak, K and Sukumar, S and Argani, P}, title = {DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma.}, journal = {International journal of cancer}, volume = {107}, number = {6}, pages = {970-975}, doi = {10.1002/ijc.11508}, pmid = {14601057}, issn = {0020-7136}, support = {P50 CA 88843/CA/NCI NIH HHS/United States ; P50 CA 89393/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Base Sequence ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Cyclin D2 ; Cyclins/*genetics ; Cytokines/*genetics ; *DNA Methylation ; DNA Primers ; Female ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Multigene Family ; Neoplasm Invasiveness ; Neoplasm Proteins/*genetics ; *Nuclear Proteins ; Receptors, Retinoic Acid/*genetics ; Reference Values ; Transcription Factors/*genetics ; *Tumor Suppressor Proteins ; Twist-Related Protein 1 ; }, abstract = {Little is known about epigenetic silencing of genes by promoter hypermethylation in lobular breast cancers. The promoter methylation status of 5 cancer-related genes (RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist) was evaluated in 2 types of lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32), and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71). By using methylation-specific PCR (MSP), 100% of ILC and 69% of LCIS cases were found to have 1 or more hypermethylated genes among the panel of 5 genes (compared to 100% IDC and 95% of DCIS). Two or more hypermethylated genes were detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A, Cyclin D2, RARbeta, and Hin-1 genes were similar, suggesting that gene silencing by promoter hypermethylation is likely to be important in both groups of diseases. Distinctly different, Twist was hyper- methylated less often in ILC (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results suggest that these 2 types of tumors share many common methylation patterns and some molecular differences. Additional studies might lend further understanding into the etiology and clinical behavior of this tumor type.}, } @article {pmid14593298, year = {2003}, author = {Paumier, A and Sagan, C and Campion, L and Fiche, M and Andrieux, N and Dravet, F and Pioud, R and Classe, JM}, title = {[Accuracy of conservative treatment for infiltrating lobular breast cancer: a retrospective study of 217 infiltrating lobular carcinomas and 2155 infiltrating ductal carcinomas].}, journal = {Journal de gynecologie, obstetrique et biologie de la reproduction}, volume = {32}, number = {6}, pages = {529-534}, pmid = {14593298}, issn = {0368-2315}, mesh = {Breast Neoplasms/pathology/*surgery ; Carcinoma, Ductal, Breast/pathology/*surgery ; Carcinoma, Lobular/pathology/*surgery ; Female ; France/epidemiology ; Humans ; Lymphatic Metastasis ; Mastectomy/statistics & numerical data ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology ; Prognosis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVES: Prognosis factors used for the management of infiltrative lobular carcinoma (ILC) are not different from those for infiltrative cuctal carcinoma (IDC). The aim of our work was to evaluate indications for conservative treatment for patients with ILC and to compare the results to those of patients with IDC. MATERIAL AND METHODS. Between 1985 and 1999 we retrospectively compared cases of 217 ILC with cases of 2155 IDC treated in Centre Rene Gauducheau, Nantes.

RESULTS: Clinical size of tumors was not different between ILC and IDC but pathological size>30 mm was more frequent for IDC. Good prognosis factors as pathological SBR classification I or II, positive hormone receptor, and the lack of axillary lymph node involvement, were more frequent for ILC. Clinical examination underestimated tumor size more frequently of ILC than IDC (p=0.02). Secondary mastectomy for involved margin was more frequent for ILC than IDC (p=0.001). For tumor with good prognosis factors, such as T<20mm, lack of lymph node involvement and SBR I or II with conservative treatment, 5 years local relapse were less frequent for ILC than IDC (p=0.025).

CONCLUSION: Parameters to validate conservative or radical treatment are the same for ILC and IDC. Diagnosis of ILC should not influence decisions regarding surgical treatment.}, } @article {pmid14580261, year = {2003}, author = {Zhang, Z and Yamashita, H and Toyama, T and Omoto, Y and Sugiura, H and Hara, Y and Wu, X and Kobayashi, S and Iwase, H}, title = {Quantitative determination, by real-time reverse transcription polymerase chain reaction, of aromatase mRNA in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {6}, pages = {R250-6}, pmid = {14580261}, issn = {1465-542X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aromatase/*genetics ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Disease-Free Survival ; Estrogen Receptor alpha ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; RNA, Messenger/genetics/*metabolism ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction/methods ; }, abstract = {BACKGROUND: Estrogen is a mitogenic factor that is implicated in the genesis and progression of breast cancer via its binding to estrogen receptor (ER)-alpha. Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase. Previous studies comparing the relative contributions from tumor cells and stromal cells to local estrogen synthesis, as assessed by immunohistochemical analysis, were quite controversial and no consistent relationship was found between the presence of aromatase and any clinicopathologic factor. In addition, previous studies into aromatase gene expression and clinicopathologic factors are limited.

METHODS: We assessed the level of expression of aromatase mRNA, using quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the breast. Associations between aromatase expression and different clinicopathologic factors were sought.

RESULTS: It was found that aromatase mRNA was expressed at significantly higher levels in patients older than 50 years, in those without axillary lymph node involvement, in those with tumor size less than 2 cm, and in ER-alpha positive tumors. However, no relationship was found between aromatase mRNA expression and any other clinicopathologic factor, including histologic grade and progesterone receptor status. Patients with high levels of expression of aromatase mRNA tended to have a better prognosis than did those patients with low expression.

CONCLUSION: These findings imply that ER-alpha and aromatase may be coexpressed in endocrine responsive patients. They may also indicate that aromatase expression could be a marker of endocrine responsiveness, and it may have prognostic implications for breast cancer progression.}, } @article {pmid14575147, year = {2003}, author = {Pavlinkova, G and Yanagawa, Y and Kikuchi, K and Iwabuchi, K and Onoé, K}, title = {Effects of histamine on functional maturation of dendritic cells.}, journal = {Immunobiology}, volume = {207}, number = {5}, pages = {315-325}, doi = {10.1078/0171-2985-00247}, pmid = {14575147}, issn = {0171-2985}, mesh = {Animals ; Antigens, CD/metabolism ; B7-2 Antigen ; Cell Differentiation/*drug effects ; Cell Line ; Dendritic Cells/cytology/*drug effects/*immunology/metabolism ; Flow Cytometry ; Histamine/*pharmacology ; Histamine Antagonists/pharmacology ; Interleukin-12/genetics/metabolism ; Lipopolysaccharides/pharmacology ; Membrane Glycoproteins/metabolism ; Mice ; Phenotype ; Receptors, Histamine/genetics/metabolism ; Spleen/cytology/drug effects/immunology ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {There is increasing evidence that histamine affects dendritic cell (DC) activation, maturation, and preference for Th1/Th2 differentiation. In this paper we report that histamine affects interleukin (IL)-12 and IL-6 production in an immature DC (iDC) line derived from murine spleen. Histamine treatment of iDC significantly increased the IL-12 p40 mRNA and protein levels compared to histamine untreated iDC. In the presence of tumor necrosis factor (TNF)-alpha histamine also increased IL-12 p40 and IL-6 production. However, histamine significantly decreased IL-12 p40 production by lipopolysaccharide (LPS)-stimulated DC in a concentration dependent manner. When expressions of histamine H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated iDC. Histamine treatment significantly increased the expression of H2R mRNA in iDC and H1R mRNA in LPS-activated DC. However, histamine treatment decreased the expression of both histamine receptors in TNF-alpha-stimulated DC. Similar results were obtained by flow cytometry with FITC-conjugated histamine. These results demonstrate that histamine can regulate the expression of its own receptors and activate iDC, which may influence subsequent functional states of mature DC in a maturation signal-dependent manner. Consequently, histamine may contribute to an immune response outcome.}, } @article {pmid14571180, year = {2003}, author = {Tasca, S and Tambussi, G and Nozza, S and Capiluppi, B and Zocchi, MR and Soldini, L and Veglia, F and Poli, G and Lazzarin, A and Fortis, C}, title = {Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from natural killer cell-mediated lysis.}, journal = {AIDS (London, England)}, volume = {17}, number = {16}, pages = {2291-2298}, doi = {10.1097/00002030-200311070-00003}, pmid = {14571180}, issn = {0269-9370}, mesh = {Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes/immunology ; Cytotoxicity, Immunologic/drug effects/*immunology ; Dendritic Cells/immunology/*virology ; Female ; Gene Products, tat/pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; HIV Infections/drug therapy/*immunology/virology ; *HIV-1 ; Humans ; Immune Tolerance ; Killer Cells, Natural/*immunology ; Male ; Middle Aged ; Monocytes/immunology ; Tumor Cells, Cultured ; Viral Load ; Viremia/immunology ; tat Gene Products, Human Immunodeficiency Virus ; }, abstract = {OBJECTIVE: To verify whether the in vitro sensitivity of immature dendritic cells (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected individuals might be correlated with HIV disease progression.

DESIGN: Both dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from 13 HIV-infected individuals early after seroconversion and not receiving highly active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV infection under HAART. The rate of NK cell-mediated killing of autologous iDC was correlated with classical parameters of HIV evolution.

METHODS: Peripheral blood monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to plastic were stimulated with granulocyte-macrophage colony stimulating factor plus IL-4 to induce their differentiation into iDC to be used as target cells in a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was stimulated with IL-2 to induce activation of NK cells to be used as effector cells.

RESULTS: During early HIV infection the extent of ex vivo lysis of monocyte-derived DC by activated autologous NK cells was inversely and directly correlated with the levels of viraemia and with the percentage of circulating CD4 T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost independently of the levels of plasma viraemia or the concurrence of HAART in chronically infected individuals. Addition of exogenous HIV Tat during the cytotoxicity assay inhibited NK cell-mediated lysis of DC.

CONCLUSIONS: NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.}, } @article {pmid14567723, year = {2003}, author = {Xu, R and Feiner, H and Li, P and Yee, H and Inghirami, G and Delgado, Y and Perle, MA}, title = {Differential amplification and overexpression of HER-2/neu, p53, MIB1, and estrogen receptor/progesterone receptor among medullary carcinoma, atypical medullary carcinoma, and high-grade invasive ductal carcinoma of breast.}, journal = {Archives of pathology & laboratory medicine}, volume = {127}, number = {11}, pages = {1458-1464}, doi = {10.5858/2003-127-1458-DAAOON}, pmid = {14567723}, issn = {1543-2165}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Medullary/*genetics ; Diagnosis, Differential ; Gene Amplification/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Genes, erbB-2 ; Genes, p53 ; Humans ; Ki-67 Antigen/biosynthesis/*genetics ; Lymphocytes, Tumor-Infiltrating/pathology ; Middle Aged ; Receptor, ErbB-2/biosynthesis/*genetics ; Receptors, Estrogen/biosynthesis/*genetics ; Receptors, Progesterone/biosynthesis/*genetics ; Tumor Suppressor Protein p53/biosynthesis/*genetics ; }, abstract = {CONTEXT: Medullary carcinoma (MC) is a special type of breast cancer that has a better prognosis than atypical medullary carcinoma (AMC) and high-grade invasive ductal carcinoma (HGIDC) with prominent lymphocytic infiltrates. What accounts for the different clinical courses of these carcinomas, despite their similar histology, is unknown. To address this issue, we performed a comparative study of amplification and overexpression of HER-2/neu and expression of several other important biochemical markers (p53, MIB1, and estrogen receptor [ER]/progesterone receptor [PR]) in these 3 cancer groups.

OBJECTIVE: To evaluate HER-2/neu, p53, MIB1, and ER/PR as markers in the differential diagnosis of MC, AMC, and HGIDC.Design.-Nine cases of MC, 13 cases of AMC, and 16 cases of HGIDC with prominent lymphocytic infiltrates were identified according to strict histologic criteria. All tests were performed on formalin-fixed, paraffin-embedded archival tissues. HER-2/neu gene amplification was examined by fluorescence in situ hybridization using PathVysion HER-2 DNA probes. Expression of HER-2/neu, p53, MIB1, and ER/PR was detected by immunohistochemistry. chi2 and Student t tests were applied for statistical analyses.

RESULTS: None of 9 cases of MC examined had either amplification or overexpression of HER-2/neu (0%). In contrast, HER-2/neu amplification was observed in AMC (46%, P <.025) and HGIDC (56%, P <.005). All 3 categories of tumors had similar percentages of expression of p53 (78% of MC, 77% of AMC, and 69% of HGIDC) and MIB1 (89% of MC, 92% of AMC, and 94% of HGIDC). Immunostaining for ER/PR was rarely positive in either MC or AMC, and there were no significant differences of expression of ER/PR between these 2 lesions (P >.05). However, the expression rate of ER/PR (31%/44%) in HGIDC is higher than in both MC (P =.05) and AMC (P =.01).

CONCLUSIONS: Medullary carcinoma of breast is distinct from AMC and HGIDC with prominent lymphocytic infiltrates in amplification and overexpression of HER-2/neu. This difference may account for its different clinical and biological behavior, and may potentially aid in diagnosis and management of these groups of patients.}, } @article {pmid14558437, year = {2003}, author = {Vergin, H and Mahr, G and Winterhalter, B and Wigand, R}, title = {Relative bioavailability and bioequivalence study of theophylline sustained release formulations.}, journal = {Arzneimittel-Forschung}, volume = {53}, number = {9}, pages = {635-639}, doi = {10.1055/s-0031-1297160}, pmid = {14558437}, issn = {0004-4172}, mesh = {Adult ; Algorithms ; Area Under Curve ; Biological Availability ; Bronchodilator Agents/*administration & dosage/*pharmacokinetics ; Chromatography, High Pressure Liquid ; Cross-Over Studies ; Delayed-Action Preparations ; Humans ; Male ; Pharmaceutical Solutions ; Theophylline/*administration & dosage/*pharmacokinetics ; Therapeutic Equivalency ; }, abstract = {The objective of this study was to determine the bioequivalence of two theophylline (CAS 58-55-9) sustained release formulations containing 400 mg (Theophyllin 400 retard Heumann, formulation A) and 375 mg (formulation C) theophylline, respectively. In addition, the relative bioavailability of the sustained release formulations in comparison to an oral solution (formulation B) was investigated. Twenty-four healthy male volunteers participated in the open randomized three-way crossover study. Multiple doses of the formulations were administered during three study periods of four days each (A: 400 mg once daily; B: 133 mg t.i.d.; C: 375 mg once daily). The absorption kinetics and the bioavailability of theophylline were investigated by model-independent and deconvolution methods. The relative bioavailability of formulation A as compared to the solution was 72%. The oral sustained release capsules did not exhibit any differences with respect to AUCss, tau and Css, max whereas differences were detected regarding tss, max and peak trough fluctuation indicating minor deviations of the plasma profiles of both formulations. However, 90% confidence intervals of the ratios of AUCss, tau and Css, max were within the respective acceptance limits. Thus, both formulations are bioequivalent considering rate and extent of absorption.}, } @article {pmid14557212, year = {2003}, author = {Li, CI and Moe, RE and Daling, JR}, title = {Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years.}, journal = {Archives of internal medicine}, volume = {163}, number = {18}, pages = {2149-2153}, doi = {10.1001/archinte.163.18.2149}, pmid = {14557212}, issn = {0003-9926}, support = {R01 CA 85913/CA/NCI NIH HHS/United States ; T32 CA 09168/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/mortality ; Aged ; Breast Neoplasms/*mortality/pathology ; Carcinoma, Ductal, Breast/*mortality ; Carcinoma, Lobular/*mortality ; Female ; Humans ; Middle Aged ; Prognosis ; Proportional Hazards Models ; SEER Program ; United States/epidemiology ; }, abstract = {BACKGROUND: Recent studies suggest that the use of combined estrogen and progestin hormone replacement therapy is associated with an increased risk of invasive lobular carcinoma (ILC), but that it has little association with risk of invasive ductal carcinoma (IDC). Also, the incidence rates of ILC have risen over the past 10 years while those of IDC have remained constant. Differences in survival rates by histologic types of tumor have been reported, but few of the published studies were population based or had adequate power to address this issue.

METHODS: We conducted a retrospective cohort study spanning the years 1974 through 1998 using data from the 9 cancer registries that have participated in the Surveillance, Epidemiology, and End Results Program since 1974. The cohort consisted of 164 958 women aged 50 to 79 years who had been diagnosed as having 1 of 7 histologic types of invasive breast cancer. Risks of mortality due to any cause were estimated using the Cox proportional hazards model.

RESULTS: Women with ILC had a risk of mortality 11% lower than women with IDC. The magnitude of this difference has increased over the past 10 years and, from 1994 through 1998, the risk of mortality was 26% lower for women with ILC. Also, the risk of mortality was between 8% and 34% lower in women with mucinous carcinoma, comedocarcinoma, or medullary, tubular, and papillary carcinomas compared with women with IDC.

CONCLUSIONS: Differences in prognosis by histologic type of breast cancer were identified. The survival rate of women 50 to 79 years old who have ILC, the cancer whose histologic type is the most closely linked with the use of combined estrogen and progestin hormone replacement therapy, is more favorable than that of women with IDC and appears to be improving over time.}, } @article {pmid14556972, year = {2003}, author = {Kikuchi, K and Yanagawa, Y and Iwabuchi, K and Onoé, K}, title = {Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells.}, journal = {Immunology letters}, volume = {89}, number = {2-3}, pages = {149-154}, doi = {10.1016/s0165-2478(03)00134-2}, pmid = {14556972}, issn = {0165-2478}, mesh = {Animals ; CD40 Antigens/*metabolism ; Dendritic Cells/*metabolism ; Interleukin-12/*biosynthesis/genetics ; Lipopolysaccharides/*metabolism ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinases/*metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Using a murine spleen-derived dendritic cell (DC) line (BC1) CD40-mediated interleukin (IL)-12 production was analyzed and compared between immature and mature DC. BC1 cells, immature DC (iDC), were maturated by treatment with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. IL-12 production of LPS-treated DC (LPS/DC) was markedly enhanced by treatment with an anti-CD40 monoclonal antibody (mAb). Although the anti-CD40 mAb also enhanced IL-12 productions of iDC and TNF-alpha-treated DC (TNF/DC), these production levels were considerably low compared with that of LPS/DC. CD40-mediated IL-12-productions by iDC and TNF/DC were significantly enhanced by treatment with PD98059, a specific inhibitor of extracellular signal-related kinase (ERK) pathway. In contrast, PD98059 showed no significant effects on CD40-mediated IL-12-production by LPS/DC. These results demonstrated that ERK pathway was involved in negative regulation of the IL-12 productions by iDC and TNF/DC but not by LPS/DC. On the other hand, SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK) pathway, completely inhibited CD40-mediated IL-12-production by iDC, while not affecting those of TNF/DC and LPS/DC. Thus, p38 MAPK pathway appeared to positively regulate the IL-12 production in iDC but not in mature DC. It seems that roles of ERK and p38 MAPK for IL-12 production are developmentally changed in murine DC.}, } @article {pmid14531536, year = {2003}, author = {Carlsson, E and Bosaeus, I and Nordgren, S}, title = {What concerns subjects with inflammatory bowel disease and an ileostomy?.}, journal = {Scandinavian journal of gastroenterology}, volume = {38}, number = {9}, pages = {978-984}, doi = {10.1080/00365520310004687}, pmid = {14531536}, issn = {0036-5521}, mesh = {Activities of Daily Living ; *Adaptation, Psychological ; Adult ; Aged ; Attitude to Health ; Female ; Humans ; Ileostomy/*psychology ; Inflammatory Bowel Diseases/complications/*psychology/surgery ; Male ; Middle Aged ; Quality of Life ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The greatest concern of patients with inflammatory bowel disease (IBD) is of having an ileostomy. The aim of this study was to describe worries and concerns in subjects with IBD and an ileostomy, and aspects of quality of life and coping strategies.

METHODS: 21 subjects with an ileostomy were included, mean age 51, range 36-65 (F/M = 12/9), Crohn disease (CD) n = 14, ulcerative colitis (UC) n = 6 and indeterminate colitis (IDC) n = 1. Worries and concerns were assessed using the rating form of IBD patient concerns (RFIPC). Health-related quality of life (HRQOL) was assessed using Short Form 36 (SF-36) and compared with a matched group for age and gender from the general population. Subjects' definition of quality of life, as well as perceived quality of life on a visual analogue scale, was evaluated. Coping strategies were investigated using the Jalowiec coping scale (JCS 40).

RESULTS: Greatest concerns were related to intimacy, access to quality medical care, energy level, loss of sexual drive, producing unpleasant odours, being a burden, ability to perform sexually, attractiveness and feelings about the body. Vitality was significantly reduced compared to controls. Subjects' definition of good quality of life mainly concerned social dimensions of life and health. Low values on perceived quality of life indicated greater concerns. Confrontational coping style was most frequently used.

CONCLUSION: The greatest concern for subjects with an ileostomy was intimacy. Vitality was reduced compared to controls. Integrating items of concern into counselling may result in greater coping ability and improved quality of life.}, } @article {pmid14528441, year = {2003}, author = {Paeng, MH and Choi, HY and Sung, SH and Moon, BI and Shim, SS}, title = {Secretory carcinoma of the breast.}, journal = {Journal of clinical ultrasound : JCU}, volume = {31}, number = {8}, pages = {425-429}, doi = {10.1002/jcu.10198}, pmid = {14528441}, issn = {0091-2751}, mesh = {Adult ; Biopsy, Fine-Needle ; Breast Neoplasms/*diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Female ; Humans ; Ultrasonography, Mammary ; }, abstract = {Secretory carcinoma of the breast is a rare but histologically distinct variant of invasive ductal carcinoma that has an indolent growth pattern and a more favorable prognosis than that of typical ductal carcinoma. We present the imaging and histopathologic findings of a case of this tumor that initially manifested as a palpable mass in the left breast of a 31-year-old woman. It appeared sonographically as a round, well-circumscribed but microlobulated hypoechoic solid mass. Secretory carcinoma of the breast may resemble other well-circumscribed breast carcinomas as well as some benign masses, including fibroadenomas. Breast imagers should be aware of this rare tumor's nonspecific imaging features and clinical implications when making a differential diagnosis of solid breast masses.}, } @article {pmid14521261, year = {2003}, author = {Mrhalová, M and Kodet, R and Kalinová, M and Hilská, I}, title = {Relative quantification of ERBB2 mRNA in invasive duct carcinoma of the breast: correlation with ERBB-2 protein expression and ERBB2 gene copy number.}, journal = {Pathology, research and practice}, volume = {199}, number = {7}, pages = {453-461}, doi = {10.1078/0344-0338-00445}, pmid = {14521261}, issn = {0344-0338}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/secondary ; Female ; *Gene Dosage ; *Gene Expression Regulation, Neoplastic ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; RNA, Messenger/metabolism ; RNA, Neoplasm/chemistry ; *Receptor, ErbB-2/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {The option to treat patients suffering from ERBB-2 protein-positive invasive duct carcinomas of the breast (IDC) with Herceptin requires a precise determination of the ERBB2 status. The aim of the study was to evaluate the ERBB2 mRNA level, placing emphasis on cases with discordant findings between ERBB-2 protein expression (IHC) and a copy number of the ERBB2 gene (FISH). Thirty-nine IDCs (21 cases IHC and FISH concordant, 15 cases moderately discordant, 3 cases markedly discordant) were investigated. ERBB2 mRNA expression was determined using quantitative real-time RT-PCR (Q-RT-PCR). IDCs with negative ERBB-2 protein and without ERBB2 gene amplification had a low ERBB2 mRNA level. Cases with 3+ overexpression of the protein and with strong gene amplification (> 10 copies/tumor cell) had a significantly increased expression of ERBB2 mRNA. In 13 of 15 IDCs with moderate discrepancies (up to 10 copies of the gene per one tumor cell/negative ERBB-2 protein; without amplification/2+ protein) mRNA was low, comparable to that in cases with negative ERBB-2 protein and without ERBB2 gene amplification. In three cases with markedly discordant findings (the gene amplified/protein negative--one case; protein 3+/no amplification--2 cases), Q-RT-PCR results were within a "normal" limit. Ineffective gene amplification and protein accumulation are suggested explanations. Q-RT-PCR revealed two cases with highly expressed ERBB2 mRNA and discordant FISH and/or IHC findings. Increased effectiveness of transcription (protein 2+/high mRNA/without the gene amplification), and combined dysregulation (protein negative/high mRNA/no amplification) are possible causes of these findings. Q-RT-PCR appears useful in clarifying borderline or discrepant IHC and FISH findings.}, } @article {pmid14520705, year = {2003}, author = {Li, CI and Malone, KE and Porter, PL and Weiss, NS and Tang, MT and Daling, JR}, title = {Reproductive and anthropometric factors in relation to the risk of lobular and ductal breast carcinoma among women 65-79 years of age.}, journal = {International journal of cancer}, volume = {107}, number = {4}, pages = {647-651}, doi = {10.1002/ijc.11465}, pmid = {14520705}, issn = {0020-7136}, support = {R01 CA072787/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; *Anthropometry ; Body Height ; Body Weight ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Case-Control Studies ; Female ; Humans ; Neoplasm Invasiveness ; Odds Ratio ; Postmenopause ; *Reproductive History ; Risk Factors ; Washington/epidemiology ; }, abstract = {Use of combined estrogen-progestin hormone replacement therapy appears to be associated with an increased risk of invasive lobular breast carcinomas (ILC) and, to a lesser degree, with risk of invasive ductal carcinoma (IDC). Conceivably, ILCs are more hormonally responsive and so may be more strongly associated than IDCs with reproductive and anthropometric characteristics that can influence hormone levels. However, few epidemiologic studies of breast cancer have evaluated these factors by histologic type. We conducted a population-based case-control study of women aged 65-79 years in western Washington State. Responses from 975 women diagnosed with breast cancer during 1997-1999 were compared to those of 1,007 controls. Associations between various reproductive and anthropometric factors and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous logistic regression. Earlier age at menarche, later age at menopause and obesity were more strongly associated with elevated risks of IDC than ILC. Alternatively, oral contraceptive use was associated with an increased risk of ILC but not IDC. Thus, the pattern of results that we observed suggest that factors influencing endogenous hormones and duration of ovarian function may be more strongly associated with IDC risk, while exogenous hormones may be more strongly associated with ILC risk.}, } @article {pmid14514971, year = {2003}, author = {Cocquyt, VF and Schelfhout, VR and Blondeel, PN and Depypere, HT and Daems, KK and Serreyn, RF and Praet, MM and Van Belle, SJ}, title = {The role of biological markers as predictors of response to preoperative chemotherapy in large primary breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {20}, number = {3}, pages = {221-231}, pmid = {14514971}, issn = {1357-0560}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*drug therapy/*metabolism/pathology ; Cathepsin D/metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Mastectomy, Segmental ; Middle Aged ; Preoperative Care ; Prospective Studies ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Remission Induction ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {The aim of this prospective study was to evaluate biological markers, their correlation with response and outcome, and the change in these markers under the influence of preoperative chemotherapy (PCT) in patients with a large primary breast cancer. One hundred and thirty-five women were treated with PCT, followed by locoregional therapy and adjuvant treatment. Estrogen receptor (ER), progesterone receptor (PgR), HER-2, p53, and cathepsin D were determined by immunohistochemistry (IHC) before and after PCT. The overall response (OR) was 70% and the pathologic complete response (pCR) was 13%. Forty-four percent of the patients could be offered breast-conserving surgery (BCS). At a median follow-up of 50 mo the overall survival is 82% and the disease-free survival is 70%. No local recurrence (LR) has developed following BCS. Invasive ductal carcinoma (IDC) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC). P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients (74% vs 53%) and ER-positive patients (75% vs 65%), but this difference did not reach statistical significance. A trend toward higher complete pathologic remission rate was seen for ER-negative patients (p = 0.0609). PgR, HER-2, and cathepsin D were not related to response. The pattern of biological markers did not change with PCT, making repeated determination useless.}, } @article {pmid14510128, year = {2001}, author = {Adegoke, BO and Badmos, KA}, title = {Acceleration of pressure ulcer healing in spinal cord injured patients using interrupted direct current.}, journal = {African journal of medicine and medical sciences}, volume = {30}, number = {3}, pages = {195-197}, pmid = {14510128}, issn = {0309-3913}, mesh = {Adult ; *Electric Stimulation Therapy/methods ; Humans ; Middle Aged ; Pressure Ulcer/etiology/nursing/*therapy ; Spinal Cord Injuries/*complications/physiopathology ; Time Factors ; *Wound Healing ; }, abstract = {This study was designed to investigate the efficacy of interrupted direct current (IDC) in augmenting routine nursing care in spinal cord injured (SCI) patients with pressure ulcers. Seven SCI patients aged 21 - 60 years (x = 43.8, S.D. = 13.9) with grade IV pressure ulcers were randomly assigned to either a group receiving routine nursing care plus IDC stimulations or a group receiving routine nursing care plus placebo IDC. Patients in both groups received 45 minutes treatment thrice weekly for 4 weeks, and had their pressure ulcers measured for surface area on day 0, at 2 weeks and at 4 weeks of the study using standard method. Percentage changes in surface area were calculated for the two groups at the different time frames. Ulcers in the IDC group had 22.2% reduction in surface area while those in the placebo IDC group had a 2.6% reduction in surface area. The reduction in size was most evident in the first two weeks of the study. The results indicate that IDC stimulation may be used in conjunction with routine nursing care to accelerate healing of grade IV pressure ulcers in SCI injured patients.}, } @article {pmid14509156, year = {2003}, author = {Greenberg, R and Barnea, Y and Schneebaum, S and Kashtan, H and Kaplan, O and Skornik, Y}, title = {Detection of hepatocyte growth factor/scatter factor receptor (c-Met) and MUC1 from the axillary fluid drainage in patients after breast cancer surgery.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {5}, number = {9}, pages = {649-652}, pmid = {14509156}, issn = {1565-1088}, mesh = {Axilla ; Biomarkers, Tumor/*isolation & purification ; Breast Neoplasms/classification/diagnosis/*surgery ; Carcinoma, Ductal, Breast/classification/diagnosis/secondary/*surgery ; Drainage/*methods ; Female ; Gene Expression Profiling ; Humans ; Lymph ; Lymph Nodes/*surgery ; Lymphatic Metastasis ; Middle Aged ; Mucin-1/*isolation & purification ; Prognosis ; Proto-Oncogene Proteins c-met/*isolation & purification ; RNA, Messenger ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer.

OBJECTIVE: To evaluate the presence and prognostic value of MUC1 and Met-hepatocyte growth factor/scatter factor in the axillary drainage of these patients.

METHODS: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-HGF/SF and beta-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status.

RESULTS: RT-PCR assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.0 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05).

CONCLUSION: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.}, } @article {pmid14505145, year = {2003}, author = {Takaori, K and Kobashi, Y and Matsusue, S and Matsui, K and Yamamoto, T}, title = {Clinicopathological features of pancreatic intraepithelial neoplasias and their relationship to intraductal papillary-mucinous tumors.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {10}, number = {2}, pages = {125-136}, doi = {10.1007/s00534-003-0756-8}, pmid = {14505145}, issn = {0944-1166}, mesh = {Aged ; Carcinoma in Situ/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/metabolism/*pathology ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Mucins/metabolism ; Pancreatic Ducts/*pathology ; Pancreatic Neoplasms/metabolism/*pathology ; }, abstract = {Pancreatic intraepithelial neoplasia (PanIN) is a recently proposed nomenclature for putative precursor lesions of pancreatic cancer, which are designated as PanIN-1 through -3 according to their increasing grade of dysplasia. A stepwise progression model of PanINs has been proposed, and multistep genetic alterations in PanINs are being investigated. PanIN-1A and PanIN-1B may remain unchanged for a long period. PanIN-3 potentially progresses toward invasive ductal carcinoma (IDC), and there are several case reports suggesting such progression. In these reported patients, PanIN-3 was found in specimens from partial pancreatectomies, and IDC manifested in the pancreatic remnant 17 months to 29 years after the surgery. We describe herein a patient with PanIN-3, in whom IDC manifested in the distal remnant pancreas 69 months after segmental pancreatectomy. Of the reported cases, including the present one, four of the patients were male and three were female, and the age at the first operation ranged from 46 to 70 years. Intraductal papillary-mucinous tumor (IPMT) is an entity that is distinct from PanIN. However, IPMTs of small size resemble PanINs morphologically. Loss of Dpc4 expression has been reported in the invasive component of IPMT, as well as in PanIN-3 and IDC. Analysis of mucin expression patterns has been reported, suggesting that, in practice, MUC1-positive MUC2-negative IPMTs may not be distinguishable from PanINs. There may be overlapping lesions between PanINs and IPMTs. Should the paradigm of the ductal origin of IDC be accepted, PanINs and a fraction of IPMTs would represent precursors of IDC.}, } @article {pmid14504186, year = {2003}, author = {Zisman, LS and Keller, RS and Weaver, B and Lin, Q and Speth, R and Bristow, MR and Canver, CC}, title = {Increased angiotensin-(1-7)-forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2.}, journal = {Circulation}, volume = {108}, number = {14}, pages = {1707-1712}, doi = {10.1161/01.CIR.0000094734.67990.99}, pmid = {14504186}, issn = {1524-4539}, support = {HL03404/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Angiotensin I/metabolism ; Angiotensin II/*metabolism ; Angiotensin-Converting Enzyme 2 ; Carboxypeptidases/*metabolism ; Cardiac Output, Low/*enzymology/metabolism ; Female ; Heart Ventricles/*enzymology/metabolism ; Humans ; Male ; Peptide Fragments/*metabolism ; Peptidyl-Dipeptidase A ; Up-Regulation ; }, abstract = {BACKGROUND: The formation of angiotensin-(1-7) from either angiotensin (Ang) I or Ang II in failing human hearts is not well understood.

METHODS AND RESULTS: Angiotensinase activity in left and right ventricular membranes from 14 idiopathic dilated cardiomyopathy (IDC), 8 primary pulmonary hypertension (PPH), and 13 nonfailing human hearts was measured with either 125I-Ang I or 125I-Ang II as substrate. Ang-(1-7)-forming activity from 125I-Ang I was inhibited by thiorphan. With 125I-Ang II as substrate, Ang-(1-7) formation was inhibited by the ACE2-specific inhibitor C16. Western blotting with an anti-ACE2 antibody confirmed the presence of ACE2. Angiotensinase activity with 125I-Ang I as substrate was increased in failing IDC left ventricles (LVs) compared with nonfailing LVs (P<0.001). Ang-(1-7)-forming activity with 125I-Ang II as substrate was increased in both failing LVs and right ventricles (RVs) of IDC hearts and only in failing RVs of PPH hearts (PPH LV, 51.12+/-5.25; PPH RV, 89.97+/-11.21; IDC LV, 139.7+/-21.96; and IDC RV, 192.7+/-5.43; NF LV, 32.89+/-5.38; NF RV 40.49+/-10.66 fmol/min per milligram (P<0.05 PPH RV versus PPH LV; P<0.05 PPH RV versus NF RV; P<0.001 IDC LV versus NF LV; P<0.001 IDC RV versus NF RV).

CONCLUSIONS: Ang-(1-7)-forming activity from both Ang I and Ang II was increased in failing human heart ventricles but was mediated by at least two different angiotensinases. The first, which demonstrated substrate preference for Ang I, was neutral endopeptidase (NEP)-like. The second was ACE2, as demonstrated by Western blotting and inhibition of activity with C16.}, } @article {pmid14504146, year = {2003}, author = {Schummer, W and Herrmann, S and Schummer, C and Funke, F and Steenbeck, J and Fuchs, J and Uhlig, T and Reinhart, K}, title = {Intra-atrial ECG is not a reliable method for positioning left internal jugular vein catheters.}, journal = {British journal of anaesthesia}, volume = {91}, number = {4}, pages = {481-486}, doi = {10.1093/bja/aeg208}, pmid = {14504146}, issn = {0007-0912}, mesh = {Aged ; Catheterization, Central Venous/*methods ; Echocardiography/*methods ; Echocardiography, Transesophageal/methods ; Female ; Humans ; Intraoperative Care/methods ; Jugular Veins/diagnostic imaging ; Male ; Middle Aged ; Postoperative Care/methods ; Prospective Studies ; Radiography ; Ultrasonography, Interventional/*methods ; }, abstract = {BACKGROUND: ECG guidance is widely used for positioning central venous catheters (CVCs) in the superior vena cava. We noticed a higher incidence of a more perpendicular angle between the catheter tip and the vessel wall after left-sided ECG-guided catheter positioning. To investigate the value of left-sided ECG guidance, we performed this prospective study.

METHODS: Of 114 patients, 53 were randomized to right and 61 to left internal jugular vein catheterization using a triple lumen catheter. Three methods to ascertain catheter tip position were sequentially applied in each patient, and the insertion depths (ID) obtained using each of the three methods were recorded: (i). ECG guidance with a Seldinger guide wire (ID-A); (ii). ECG guidance with saline 10% used as an exploring electrode (ID-B); (iii). from position ID-B, the catheter was rotated and advanced until all three lumina could be aspirated easily. The catheter was fixed in that position (ID-C). To determine final catheter tip position, intraoperative transoesophageal echocardiography (TOE) and a postoperative chest X-ray (CXR) were performed.

RESULTS: The depth of insertion of a catheter using the three methods varied significantly in left-sided (P<0.001), but not in right-sided catheters. Forty-eight of 57 (84%) left-sided CVCs, correctly positioned according to ECG guidance, had to be advanced further to achieve free aspiration through all three lumina. By this stage, five of the catheter tips had been positioned in the upper right atrium as demonstrated by TOE. There were 13 malpositions (23%) after left-sided insertion. In nine catheter malpositions, undetected by ECG guidance, the angle between the catheter tip and the lateral wall of the superior vena cava exceeded 40 degrees on CXR.

CONCLUSIONS: Intra-atrial ECG does not detect the junction between the superior vena cava and right atrium. It is not a reliable method for confirming position of left-sided CVCs. Post-procedural CXRs are recommended for left-sided, but not right-sided CVCs.}, } @article {pmid14502779, year = {2003}, author = {Leidenius, MH and Krogerus, LA and Toivonen, TS and Von Smitten, KJ}, title = {The feasibility of intraoperative diagnosis of sentinel lymph node metastases in breast cancer.}, journal = {Journal of surgical oncology}, volume = {84}, number = {2}, pages = {68-73}, doi = {10.1002/jso.10296}, pmid = {14502779}, issn = {0022-4790}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/pathology/surgery ; Carcinoma, Ductal, Breast/*diagnosis/secondary/surgery ; Carcinoma, Lobular/*diagnosis/secondary/surgery ; Feasibility Studies ; Humans ; Intraoperative Period ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Prospective Studies ; Sensitivity and Specificity ; *Sentinel Lymph Node Biopsy ; }, abstract = {BACKGROUND AND OBJECTIVES: The aim of the study was to analyse in detail the feasibility of intraoperative assessment of sentinel lymph nodes in breast cancer.

METHODS: Altogether 139 consecutive breast cancer patients with metastases in axillary sentinel nodes were included in a prospective study. A combination of imprint cytology and frozen section was used as the method of intraoperative diagnosis of sentinel node metastases. The definite postoperative evaluation of the sentinel nodes was taken as the gold standard.

RESULTS: The overall sensitivity of intraoperative diagnosis was 83%, reaching 81% if the intraoperative assessment had been limited to the two first retrieved sentinel nodes. False negative (FN) findings were more common in connection with invasive lobular carcinoma (28%) than with invasive ductal carcinoma (8%) (P < 0.01) as well as in connection with micro-metastases, in 38% of the cases, compared to the larger metastases, 6% (P < 0.00005).

CONCLUSIONS: Intraoperative examination of sentinel lymph nodes enables breast surgery, axillary staging, and treatment in the same operation in a substantial proportion of breast cancer patients. Hospital costs as well as workload in the pathology laboratory may be reduced, limiting the intraoperative assessment to the two first retrieved nodes.}, } @article {pmid14501369, year = {2003}, author = {Nishino, M and Hayakawa, K and Yamamoto, A and Nakamura, Y and Morimoto, T and Mukaihara, S and Urata, Y}, title = {Multiple enhancing lesions detected on dynamic helical computed tomography-mammography.}, journal = {Journal of computer assisted tomography}, volume = {27}, number = {5}, pages = {771-778}, doi = {10.1097/00004728-200309000-00015}, pmid = {14501369}, issn = {0363-8715}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*diagnostic imaging/*pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Contrast Media ; Female ; Humans ; Imaging, Three-Dimensional ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Tomography, Spiral Computed/*methods ; }, abstract = {OBJECTIVES: To review pathologic diagnoses of multiple enhancing lesions in a unilateral breast detected on dynamic helical computed tomography (CT)-mammography and to correlate imaging findings with pathologic results.

METHODS: From May 1998 to July 2001, preoperative contrast-enhanced helical CT scanning of the breast was performed in 200 female patients clinically diagnosed with breast cancer. The patients were scanned in the prone position in a specially designed CT-compatible device, with rapid intravenous bolus injection of 100 mL contrast material. Three-dimensional maximum intensity projection images were reconstructed. The cases with multiple enhancing lesions in a unilateral breast were retrospectively reviewed. The maximum diameter of the largest stain in each breast was measured, the patterns of multiple enhancing lesions were classified, and imaging findings were correlated with surgical and pathologic outcomes.

RESULTS: Twenty-five of 200 (12.5%) patients (age range: 39-86 years, mean age: 56 years) showed multiple stains on CT-mammography. Two patients showed multiple stains in bilateral breasts. The maximum diameter of the largest stain in each breast ranged from 5 to 55 mm (average: 22 mm). Among cases with multiple stains, 21 (78%) were shown to be invasive ductal carcinoma with multiple satellite cancer nodules. Four cases were ductal carcinoma in situ with multiple satellite nodules. One case revealed multiple fibroadenomas, and another showed intraductal papilloma.

CONCLUSIONS: Multiple enhancing lesions on CT-mammography in patients with breast cancer were relatively common, and most of them represented multiple cancer lesions. Dynamic CT-mammography is potentially useful in evaluating the spread of breast cancer.}, } @article {pmid12968544, year = {2003}, author = {Muttarak, M and Pojchamarnwiputh, S and Chaiwun, B}, title = {Breast cancer in women under 40 years: preoperative detection by mammography.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {32}, number = {4}, pages = {433-437}, pmid = {12968544}, issn = {0304-4602}, mesh = {Adult ; Age Factors ; Breast Neoplasms/mortality/*pathology/*surgery ; Cohort Studies ; Female ; Humans ; Incidence ; Mammography/*methods ; Mass Screening/*methods ; Neoplasm Invasiveness/*pathology ; Preoperative Care ; Retrospective Studies ; Risk Assessment ; Sensitivity and Specificity ; Survival Analysis ; United States/epidemiology ; }, abstract = {INTRODUCTION: This article assesses the diagnostic sensitivity of mammography in the preoperative detection of breast cancer in young women.

MATERIALS AND METHODS: We retrospectively reviewed 1010 women with breast carcinoma between January 1996 and September 2002. The patients were identified from pathological reports. Of these, 237 women were below 40 years of age, accounting for 23.5% of all breast cancers. Only 76 of 237 patients had mammograms performed prior to surgery. Seventy-five of the 76 patients also had ultrasonography performed. Histological types were reviewed and the proportions of each type were compared with those found in a consecutive series of 773 breast carcinomas in women above 40 years of age seen during the same period in our hospital. The breast patterns, as seen on mammograms, were classified as follows: fatty, scattered fibroglandular, heterogeneously dense and homogeneously dense. Specific features of a mass, microcalcifications, architectural distortion and asymmetrical density were evaluated.

RESULTS: Of the 76 patients who had mammograms performed prior to surgery, 81 cancers were found. The patients' age ranged from 25 to 40 years, with a mean of 36.4 years. The breast parenchymal patterns were homogeneously dense in 6.6%, heterogeneously dense in 67.1% and had scattered fibroglandular density in 26.3%. Abnormal mammographical findings were present in 93.8%. The most common mammographical findings were mass in 60% and microcalcifications, with or without associated breast abnormality, in 28.7%. The most frequent tumour (82.7%) was invasive ductal carcinoma, which is not significantly different to those found in older women (P = 0.895). Ultrasonography showed solid masses in 73 patients and was negative in the other 2 patients.

CONCLUSION: Mammography is a useful imaging technique in providing preoperative detection and diagnosis of breast carcinoma in women below 40 years of age with clinical suspicion of malignancy. Mass and microcalcifications are the most common abnormal mammographical findings and invasive ductal carcinoma is the most common tumour found in our study.}, } @article {pmid12967783, year = {2003}, author = {Ichim, TE and Zhong, R and Min, WP}, title = {Prevention of allograft rejection by in vitro generated tolerogenic dendritic cells.}, journal = {Transplant immunology}, volume = {11}, number = {3-4}, pages = {295-306}, doi = {10.1016/S0966-3274(03)00048-0}, pmid = {12967783}, issn = {0966-3274}, mesh = {Animals ; Antigen Presentation ; Dendritic Cells/chemistry/immunology/*transplantation ; Fas Ligand Protein ; Graft Rejection/immunology/*prevention & control ; Immune Tolerance ; Interleukin-12/genetics ; Killer Cells, Natural/immunology ; Lymphocyte Subsets/immunology ; Major Histocompatibility Complex ; Membrane Glycoproteins/genetics ; Mice ; NF-kappa B/antagonists & inhibitors ; Transfection ; *Transplantation Tolerance ; }, abstract = {Achieving immunological tolerance in transplantation has been a long sought-after goal since the 1960s. It is, therefore, interesting that the dendritic cells (DC), which are classically known as the most potent stimulators of T cell activation, are now also considered putative tools for tolerance induction. In line with this, much work has been performed using DC for vaccination and immune stimulation. Recently, great interest has been generated regarding the ability of DC to act as immune regulatory cells. Specific subsets of DC or immature DC (iDC) appear to be responsible for maintaining self-tolerance. In this review we will highlight our efforts at elucidating the contribution of DC in transplant tolerant in mice. Specifically, four strategies will be outlined that are currently being used for the generation of DC that have tolerogenic properties in the prevention of allograft rejection. The present study demonstrates that modulated iDC with blunted T cell stimulatory or antigen presentation abilities can afford transplant tolerance by minimizing T cell activation and proinflammatory cytokine production. Moreover, in an alternate strategy, normally matured DC have also been modulated such that alloreactive T cells are specifically targeted for deletion.}, } @article {pmid12961959, year = {2003}, author = {Makdissi, J and Barez, R and Whaites, E and Brown, J}, title = {Case report--Scanora imaging of an unusual unerupted tooth located entirely below the inferior dental canal.}, journal = {Journal of the Irish Dental Association}, volume = {49}, number = {2}, pages = {43-46}, pmid = {12961959}, issn = {0021-1133}, mesh = {Bicuspid ; Female ; Humans ; Mandible/*diagnostic imaging ; Middle Aged ; Radiography, Dental, Digital ; Radiography, Panoramic ; Tomography, Spiral Computed ; Tooth, Unerupted/*diagnostic imaging ; }, abstract = {We present an unusual case of an unerupted tooth located beneath the inferior dental canal (IDC) seen as an incidental finding on a dental panoramic radiograph (DPR). An unerupted premolar was identified on the DPR lying horizontally and located entirely below the inferior dental canal in the first and second molar region. The crown was distally orientated and was somewhat demineralised. As this unerupted tooth appeared to have an intimate relationship with the inferior dental canal, which in turn had a close relationship with the distal roots of the lower left first molar, this relationship was investigated further. Spiral tomography using Soredex's Scanora unit was used to obtain three contiguous 2 mm thick cross-sectional images of the area, which showed the separation of the inferior dental canal from both the first molar tooth above and the unerupted premolar. This case highlights the role of Scanora cross-sectional imaging in establishing accurately the relationship between teeth and the inferior dental canal and to document the unusual position of this unerupted tooth.}, } @article {pmid12939642, year = {2003}, author = {Nagorsen, D and Panelli, M and Dudley, ME and Finkelstein, SE and Rosenberg, SA and Marincola, FM}, title = {Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells.}, journal = {Gene therapy}, volume = {10}, number = {20}, pages = {1754-1765}, pmid = {12939642}, issn = {0969-7128}, support = {Z01 SC003811-32//Intramural NIH HHS/United States ; }, mesh = {Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; Cancer Vaccines ; Cell Line ; Clone Cells ; Dendritic Cells/*immunology ; Epitopes/*immunology ; Flow Cytometry ; Genetic Therapy/*methods ; Genetic Vectors/*administration & dosage ; HLA-A Antigens/*immunology ; HLA-A2 Antigen ; Humans ; Interferon-gamma/immunology ; Melanoma/immunology/therapy ; Membrane Glycoproteins/genetics ; Neoplasm Proteins/genetics ; Peptides ; Receptors, Antigen, T-Cell/immunology ; Vaccinia virus/*genetics ; gp100 Melanoma Antigen ; }, abstract = {Recombinant expression vectors represent a powerful way to deliver whole antigens (Ags) for immunization. Sustained Ag expression in vector-infected dendritic cells (DC) combines Ag-specific stimulation with powerful costimulation and, simultaneously, through 'self-selection' of ad hoc epitopes broadens the scope of immunization beyond restrictions posed by individual patients' human leukocyte antigen (HLA) phenotype. In this study, therefore, we evaluated the efficiency of a recombinant vaccinia virus encoding the gp100/PMel17 melanoma Ag (rVV-gp100) to infect immature (iDC) or mature dendritic cells (mDC) derived from circulating mononuclear cells and the effect of infection on their status of maturation. In addition, we tested the ability of rVV-gp100-infected iDC and mDC to present the HLA-A*0201-associated gp100:209-217 epitope (g209). Irrespective of status of maturation, rVV-gp100 infection induced gp100 expression while only partially reversing the expression of some maturation markers. However, endogenous presentation of the wild-type g209 epitope was inefficient. The low efficiency was epitope-specific since infection of DC with rVV encoding a gp100 construct containing the modified gp100:209-217 (210M) (g209-2M) epitope characterized by high binding affinity for HLA-A*0201 restored efficient Ag presentation. Presentation of an HLA-class II-associated epitope and cytokine release by DC was not altered by rVV infection. Thus, Ag expression driven by rVV may be an efficient strategy for whole Ag delivery. However, since the effectiveness of Ag processing and presentation is subject to stringent HLA/epitope pairing, and for other yet undefined rules, the assumption that whole Ag delivery may circumvent HLA restriction is incorrect and recombinant expression vectors encoding well-characterized polyepitopic constructs may prove more effective.}, } @article {pmid12931549, year = {2003}, author = {Ventura, K and Cangiarella, J and Lee, I and Moreira, A and Waisman, J and Simsir, A}, title = {Aspiration biopsy of mammary lesions with abundant extracellular mucinous material. Review of 43 cases with surgical follow-up.}, journal = {American journal of clinical pathology}, volume = {120}, number = {2}, pages = {194-202}, doi = {10.1309/2MKQ-RJ3D-LPMT-4LJA}, pmid = {12931549}, issn = {0002-9173}, mesh = {Adenocarcinoma, Mucinous/classification/*pathology/surgery ; Adult ; Aged ; Aged, 80 and over ; *Biopsy, Needle ; Breast Neoplasms/classification/*pathology/surgery ; Carcinoma, Ductal, Breast/classification/*pathology/surgery ; Diagnosis, Differential ; Extracellular Space ; Female ; Fibroadenoma/classification/*pathology/surgery ; Fibrocystic Breast Disease/classification/*pathology/surgery ; Follow-Up Studies ; Humans ; Middle Aged ; Mucocele/classification/pathology/surgery ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and "suspicious" for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia.}, } @article {pmid12929205, year = {2003}, author = {Bozdech, Z and Llinás, M and Pulliam, BL and Wong, ED and Zhu, J and DeRisi, JL}, title = {The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.}, journal = {PLoS biology}, volume = {1}, number = {1}, pages = {E5}, pmid = {12929205}, issn = {1545-7885}, support = {/WT_/Wellcome Trust/United Kingdom ; U01 AI053862/AI/NIAID NIH HHS/United States ; AI53862/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antimalarials/pharmacology ; Chromosome Mapping ; Chromosomes/ultrastructure ; Erythrocytes/*parasitology ; Gene Expression Regulation ; *Gene Expression Regulation, Developmental ; Genes, Protozoan ; Genome ; Genome, Protozoan ; Humans ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides/chemistry ; Open Reading Frames ; Plasmodium falciparum/*metabolism ; Plastids ; Protozoan Proteins ; RNA, Messenger/metabolism ; Time Factors ; *Transcription, Genetic ; }, abstract = {Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200-300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a "just-in-time" manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates.}, } @article {pmid12927045, year = {2003}, author = {Kato, M and Kitayama, J and Kazama, S and Nagawa, H}, title = {Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {5}, pages = {R144-50}, pmid = {12927045}, issn = {1465-542X}, mesh = {Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/pathology/*secondary ; Chemokine CXCL12 ; Chemokines, CXC/biosynthesis/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology ; Lymphatic Metastasis/pathology ; Receptors, CXCR4/*biosynthesis/genetics ; }, abstract = {BACKGROUND: The stromal cell-derived factor-1/CXC chemokine receptor-4 (SDF-1/CXCR4) signal has been shown to be important in various immunological reactions. Recent studies have suggested that CXCR4 is expressed in certain cancer cells and that they use this chemokine receptor efficiently for metastasis formation.

METHOD: The expression of CXCR4 was evaluated by immunohistochemical study in 79 surgically resected invasive ductal carcinomas, and the relation between the staining pattern and clinicopathological features was examined.

RESULTS: CXCR4 was diffusely and homogeneously expressed in 59 cancers, which were further divided into 28 high-expression and 31 low-expression cancers by their staining intensity. The other 20 cancers showed heterogeneous immunoreactivity in tumor tissue, which was defined as focal type. In comparison with the diffuse type, focal type tumors showed significantly more extensive lymph node metastasis, because the number and extent of metastatic nodes were larger in the focal than the diffuse type. In the diffuse type, the rate of node-positive cases did not show a difference in staining intensity. However, high-CXCR4 tumors showed more extensive nodal metastasis in comparison with low-expression tumors. In contrast, the expression pattern of CXCR4 did not have a significant correlation with hematogeneous metastasis. The overall survival of these patients tended to be better in the diffuse type than in the focal type, although the difference was not statistically significant.

CONCLUSION: The expression pattern of CXCR4 was significantly correlated with the degree of lymph node metastasis in breast cancers. Our data suggest that CXCR4 might be particularly important in facilitating metastasis through the lymphatic system.}, } @article {pmid12926055, year = {2003}, author = {Watanabe, O and Shimizu, T and Imamura, H and Kinoshita, J and Utada, Y and Okabe, T and Kimura, K and Hirano, A and Yoshimatsu, K and Aiba, M and Ogawa, K}, title = {Expression of cyclooxygenase-2 in malignant and benign breast tumors.}, journal = {Anticancer research}, volume = {23}, number = {4}, pages = {3215-3221}, pmid = {12926055}, issn = {0250-7005}, mesh = {Breast Neoplasms/*enzymology/pathology ; Carcinoma in Situ/enzymology ; Carcinoma, Ductal, Breast/enzymology ; Cyclooxygenase 2 ; Female ; Fibroadenoma/enzymology ; Humans ; Immunohistochemistry ; Isoenzymes/*biosynthesis ; Membrane Proteins ; Papilloma, Intraductal/enzymology ; Prostaglandin-Endoperoxide Synthases/*biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Cyclooxygenase-2 (COX-2) is reported to play an important role in carcinogenesis. We examined COX-2 expression in patients with breast cancer and benign breast tumors. Immunohistochemical staining revealed a high level of COX-2 expression in malignant lesions of invasive ductal carcinoma (IDC) at a rate of 40% and a low level of expression in 15% of adjacent normal-appearing breast epithelia. Similarly, in ductal carcinoma in situ (DCIS), a high level of COX-2 expression was found in 80% of malignant lesions and a low level of expression in 50% of normal epithelia. Reverse transcriptional polymerase chain reaction (RT-PCR) performed in 7 of these cases disclosed that COX-2 expression was restricted to the malignant lesion. Further, all 10 cases of fibroadenoma and 10 cases of intraductal papilloma, both of which are benign tumors, had a high level of COX-2 expression. When overexpression of COX-2 was analyzed in relation to the clinicopathological features of the patients, no characteristic correlation was noted. Our results demonstrated that COX-2 is expressed in mammary tissue during tumorigenesis of the breast gland, suggesting that the cyclooxygenase isoenzyme may be a target for the prevention and treatment of breast cancer.}, } @article {pmid12924421, year = {2003}, author = {Kijima, Y and Owaki, T and Yoshinaka, H and Aikou, T}, title = {Synchronous bilateral breast cancer with Paget's disease and invasive ductal carcinoma: report of a case.}, journal = {Surgery today}, volume = {33}, number = {8}, pages = {606-608}, doi = {10.1007/s00595-003-2549-8}, pmid = {12924421}, issn = {0941-1291}, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Mastectomy, Modified Radical ; Mastectomy, Segmental ; Middle Aged ; Neoplasms, Multiple Primary/pathology/surgery ; Nipples/pathology ; Paget's Disease, Mammary/*pathology/surgery ; }, abstract = {We report a case of synchronous bilateral breast cancer with Paget's disease and invasive ductal carcinoma. A 60-year-old Japanese woman presented with an 8-month history of discharge from the left nipple with eczema and itching. Mammography showed grouped fine calcification in the right breast, which was highly suggestive of right breast carcinoma with an intraductal component. Ultrasonography did not reveal any mass lesions in the bilateral breasts, and computed tomography and bone scintigraphy showed no site of distant metastasis. We performed a modified radical mastectomy for Paget's disease in the left breast and breast-conserving surgery for ductal carcinoma in the right breast. The histological diagnosis was Paget's disease in the left breast and invasive ductal carcinoma with a predominant intraductal component in the right breast. There was no metastasis in any of the 24 left axillary lymph nodes resected. We also gave her postoperative adjuvant chemoendocrine therapy, comprised of tamoxifen (20 mg) and UFT (uracil/tegafur) (400 mg)daily. The patient has been disease-free for 4 years since her operation.}, } @article {pmid12905618, year = {2003}, author = {Sun, Q and Zhou, YD and Huang, HY}, title = {[Diagnosis and treatment of Paget's disease of the breast: report of 33 cases].}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {25}, number = {1}, pages = {93-95}, pmid = {12905618}, issn = {1000-503X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Diagnostic Errors ; Female ; Humans ; Middle Aged ; Paget's Disease, Mammary/*diagnosis/surgery ; }, abstract = {OBJECTIVE: To study the clinical features and histologic criteria of Paget's disease of breast, and evaluate the potential prognostic factors for better appropriate treatment strategies.

METHODS: Thirty-three patients treated for Paget's disease of breast were reviewed retrospectively.

RESULTS: The median age of diagnosis was 57 years. Twenty-nine patients were treated by modified radical mastectomy, 4 cases by mastectomy. Twenty-three (69.7%) patients had underlying carcinoma. Twenty-six (78.8%) patients did not have a palpable breast mass, 10 of them was simple Paget's disease, eight had ductal carcinoma in situ, eight had invasive ductal carcinoma. Seven patients had a palpable breast mass, and none of them was simple Paget's disease, except one of them had ductal carcinoma in situ, six had invasive ductal carcinoma.

CONCLUSIONS: Most patients with Paget's disease had associated breast carcinoma. Paget's disease of the breast with a palpable breast mass is more likely to be accompanied by an invasive ductal carcinoma and had a poor prognosis. Patients with any nipple complaints deserve a serious investigation.}, } @article {pmid12894577, year = {2003}, author = {Seth, A and Kitching, R and Landberg, G and Xu, J and Zubovits, J and Burger, AM}, title = {Gene expression profiling of ductal carcinomas in situ and invasive breast tumors.}, journal = {Anticancer research}, volume = {23}, number = {3A}, pages = {2043-2051}, pmid = {12894577}, issn = {0250-7005}, mesh = {Biomarkers, Tumor/biosynthesis/genetics ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carrier Proteins/biosynthesis/genetics ; Disease Progression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; *Insulin-Like Growth Factor Binding Proteins ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; Up-Regulation ; }, abstract = {UNLABELLED: Comparative and functional genomics are powerful tools to advance the understanding of the molecular basis of cancer. It is believed that genes are epigenetically regulated and, thus, each tumor type and stage will be characterized by a gene expression fingerprint. In this study we identified genes that are differentially expressed in ductal carcinoma in situ and invasive ductal carcinoma of the breast. To isolate genes that are associated with progression of breast cancer we performed differential display and subtractive cloning procedures using matched RNA from normal and tumor tissue. cDNA microarray analysis generated gene expression profiles typical of the transition from in situ to invasive breast cancer when we used mRNA extracted from a case of low- to intermediate-grade DCIS and a case of high-grade DCIS/IDC. cDNAs from these samples were the probes in a cDNA microarray hybridization to 9183 unique cDNAs representing 8507 genes. Signals from both transcriptomes were obtained for 8083 genes, and the balanced differential expression values between pure DCIS and DCIS/invasive tumors revealed 303 distinct cDNAs with a ratio of > 2. Interferon inducible genes were found to be expressed at the highest level in the pure DCIS sample. Genes most abundantly expressed in the invasive tumor were immunoglobulin heavy constant gamma 3 and calgranulin B. Further analysis of RNA and protein expression in breast tumor cell lines and patient tissue samples revealed that: IGFBP-rP1 is down-regulated in invasive tumors whereas cyclin I protein is regulated by ubiquitination and is associated with ER-negative breast cancers.

CONCLUSION: The known and novel genes discussed here represent targets for molecular characterization during breast cancer development as well as for designing novel strategies for diagnosis and treatment.}, } @article {pmid12891210, year = {2003}, author = {Grimm, W and Rudolph, S and Christ, M and Pankuweit, S and Maisch, B}, title = {Prognostic significance of morphometric endomyocardial biopsy analysis in patients with idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {146}, number = {2}, pages = {372-376}, doi = {10.1016/S0002-8703(03)00148-0}, pmid = {12891210}, issn = {1097-6744}, mesh = {Adolescent ; Adult ; Aged ; Biopsy ; Cardiomyopathy, Dilated/complications/mortality/*pathology ; Death, Sudden, Cardiac/etiology ; Female ; Follow-Up Studies ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Myocardium/*pathology ; Prognosis ; Tachycardia, Ventricular/etiology ; Ventricular Fibrillation/etiology ; }, abstract = {BACKGROUND: To date, considerable controversy exists on the prognostic significance of morphometric endomyocardial biopsy findings in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS: Quantitative analyses of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters of left ventricular endomyocardial biopsy specimens were performed in 124 patients with IDC.

RESULTS: During 51 +/- 22 months follow-up after left ventricular endomyocardial biopsy, major arrhythmic events, defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death, were observed in 24 patients (19%). Death from any cause or heart transplant was observed in 39 patients (31%). The amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters determined from left ventricular endomyocardial biopsy specimens did not differ significantly between patients with and patients without major arrhythmic events or between patients with and patients without transplant-free survival during follow-up.

CONCLUSIONS: Quantitative analysis of the amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters in left ventricular endomyocardial biopsy specimens does not appear to be useful for predicting arrhythmic events and transplant-free survival in IDC.}, } @article {pmid12890042, year = {2003}, author = {Grimm, W and Schmidt, G and Maisch, B and Sharkova, J and Müller, HH and Christ, M}, title = {Prognostic significance of heart rate turbulence following ventricular premature beats in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of cardiovascular electrophysiology}, volume = {14}, number = {8}, pages = {819-824}, doi = {10.1046/j.1540-8167.2003.03085.x}, pmid = {12890042}, issn = {1045-3873}, mesh = {Age Distribution ; Cardiomyopathy, Dilated/*diagnosis/*epidemiology/mortality/surgery ; Comorbidity ; Disease-Free Survival ; Electrocardiography, Ambulatory/*methods ; Germany/epidemiology ; Heart Transplantation/*mortality/statistics & numerical data ; Humans ; Middle Aged ; Predictive Value of Tests ; Prevalence ; Prognosis ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Sex Distribution ; Single-Blind Method ; Survival Analysis ; Ventricular Premature Complexes/*diagnosis/*epidemiology/mortality/surgery ; }, abstract = {UNLABELLED: Heart Rate Turbulence in Dilated Cardiomyopathy.

INTRODUCTION: The aim of this study was to investigate the prognostic significance of heart rate turbulence (HRT) characterized by HRT onset and slope after ventricular premature beats in patients with idiopathic dilated cardiomyopathy (IDC).

METHODS AND RESULTS: Blinded HRT analysis was performed in 242 patients with IDC who were enrolled in the Marburg Cardiomyopathy database between 1992 and 2000. During 41 +/- 23 months of follow-up, 54 patients (22%) died or underwent heart transplant. On Cox univariate regression analysis, abnormal HRT onset, HRT slope, HRT onset combined with HRT slope, left ventricular (LV) ejection fraction, LV size, and New York Heart Association (NYHA) functional class III showed a significant association with total mortality or the need for heart transplant. On multivariate analysis, abnormal HRT onset identified patients without transplant-free survival, as did LV size and NYHA class III heart failure. Major arrhythmic events were observed in 42 patients (17%) during follow-up. On univariate analysis, abnormal HRT onset, HRT onset combined with HRT slope, male sex, NYHA class III, LV ejection fraction, and LV size were associated with a higher incidence of major arrhythmic events. On multivariate analysis, only LV ejection fraction remained as a significant arrhythmia risk predictor, with a relative risk of 2.2 per 10% decrease in ejection fraction (95% confidence interval 1.5-3.2).

CONCLUSION: In this selected patient population with IDC, HRT onset is a significant predictor of transplant-free survival, as are LV size and NYHA class. For arrhythmia risk stratification, however, only LV ejection fraction remained a significant risk predictor on multivariate analysis.}, } @article {pmid12881585, year = {2003}, author = {Jong, RA and Yaffe, MJ and Skarpathiotakis, M and Shumak, RS and Danjoux, NM and Gunesekara, A and Plewes, DB}, title = {Contrast-enhanced digital mammography: initial clinical experience.}, journal = {Radiology}, volume = {228}, number = {3}, pages = {842-850}, doi = {10.1148/radiol.2283020961}, pmid = {12881585}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; *Contrast Media/administration & dosage ; Female ; Humans ; Injections, Intravenous ; *Iohexol ; *Mammography ; Middle Aged ; *Radiographic Image Enhancement ; }, abstract = {PURPOSE: To investigate the potential of using intravenous contrast material with full-field digital mammography to facilitate the detection and characterization of lesions in the breast.

MATERIALS AND METHODS: Twenty-two women scheduled for biopsy because they were suspected of having abnormalities at breast imaging underwent imaging with contrast material-enhanced digital mammography. Six sequential images of the affected breast were obtained, with a contrast agent injected intravenously between the time the first and second images were obtained. Image processing included registration and logarithmic subtraction. Lesions were evaluated for the presence, morphology, and kinetics of enhancement. Lesion type, size, and pathologic findings were correlated with the findings at contrast-enhanced digital mammography.

RESULTS: At contrast-enhanced digital mammography, enhancement was observed in eight of 10 patients with biopsy-proved cancers. In one case of ductal carcinoma in situ and one case of invasive ductal carcinoma, enhancement was not observed. No enhancement was seen in seven of 12 cases in which lesions were suspected of being malignant at initial imaging but were benign. Morphology generally correlated with the pathologic diagnosis. The kinetics of lesion enhancement showed similarity to that seen with gadolinium-enhanced magnetic resonance imaging but was not consistent.

CONCLUSION: The results of this preliminary study suggest that contrast-enhanced digital mammography potentially may be useful in identification of lesions in the mammographically dense breast. Further investigation of contrast-enhanced digital mammography as a diagnostic tool for breast cancer is warranted.}, } @article {pmid12869683, year = {2003}, author = {Malich, A and Sauner, D and Marx, C and Facius, M and Boehm, T and Pfleiderer, SO and Fleck, M and Kaiser, WA}, title = {Influence of breast lesion size and histologic findings on tumor detection rate of a computer-aided detection system.}, journal = {Radiology}, volume = {228}, number = {3}, pages = {851-856}, doi = {10.1148/radiol.2283011906}, pmid = {12869683}, issn = {0033-8419}, mesh = {Breast/*pathology ; Breast Neoplasms/diagnostic imaging/*pathology ; Calcinosis/pathology ; *Diagnosis, Computer-Assisted ; False Positive Reactions ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To evaluate associations between histopathologic findings, tumor size, and detection rate of malignant mammographic findings by using a computer-aided detection (CAD) system.

MATERIALS AND METHODS: The study included 208 mammographically detected histologically proven malignant breast lesions in 208 women. Findings were 150 masses and 114 microcalcifications; 56 lesions showed both findings; 94 lesions, mass only; and 58 lesions, microcalcification only. CAD was used to evaluate mammograms in two views retrospectively. Also, corresponding histopathologic findings and lesion size were evaluated. CAD marks were considered positive if, on at least one view, they correctly identified the corresponding mammographic lesion location.

RESULTS: Ninety percent (135 of 150) of masses and 93.0% (106 of 114) of microcalcifications were marked correctly by the CAD system. Overall tumor detection rate was 93.8% (195 of 208). Size-related detection rate for masses was 83.3% (25 of 30) for lesions up to 10 mm, 100% (45 of 45) for lesions 11-20 mm, 100% (46 of 46) for lesions 21-30 mm, 83.3% (10 of 12) for lesions 31-40 mm, and 52.9% (nine of 17) for lesions larger than 40 mm. Size-related tumor detection rate for microcalcifications was 92.5% (37 of 40) for microcalcifications up to 10 mm, 93.1% (27 of 29) for lesions 11-20 mm, 100% (20 of 20) for lesions 21-30 mm, 87.5% (seven of eight) for lesions 31-40 mm, and 88.2% (15 of 17) for larger microcalcifications. Detection rates for mammographically visible masses (invasive ductal carcinoma, invasive lobular carcinoma, invasive tubular carcinoma, noninvasive cancers, mucinoid cancers, and others) were 92.3% (84 of 91), 89.3% (25 of 28), 75.0% (six of eight), 100% (15 of 15), 33.3% (one of three), and 80.0% (four of five), respectively. Detectability rates for mammographically visible areas suspicious for microcalcifications (invasive ductal carcinoma, invasive lobular carcinoma, invasive tubular carcinoma, and noninvasive cancers) were 92.3% (60 of 65), 100% (eight of eight), 100% (five of five), and 91.9% (31 of 34), respectively. Highest overall detection rates were observed for invasive ductal carcinomas (96.6% [112 of 116]) and noninvasive cancers (92.9% [39 of 42]).

CONCLUSION: Highest detection rates were observed for 10-30-mm tumor masses and for invasive ductal carcinomas and noninvasive cancers.}, } @article {pmid12866579, year = {2003}, author = {Giardina, C and Serio, G and Lepore, G and Lettini, T and Dalena, AM and Pennella, A and D'Eredità, G and Valente, T and Ricco, R}, title = {Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {22}, number = {2}, pages = {279-288}, pmid = {12866579}, issn = {0392-9078}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Cell Differentiation ; Cell Nucleus/metabolism ; Female ; Humans ; Middle Aged ; Mitosis ; Multivariate Analysis ; }, abstract = {Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.}, } @article {pmid12860273, year = {2003}, author = {Kapucuoglu, N and Coban, T and Raunio, H and Pelkonen, O and Edwards, RJ and Boobis, AR and Iscan, M}, title = {Immunohistochemical demonstration of the expression of CYP2E1 in human breast tumour and non-tumour tissues.}, journal = {Cancer letters}, volume = {196}, number = {2}, pages = {153-159}, doi = {10.1016/s0304-3835(03)00277-5}, pmid = {12860273}, issn = {0304-3835}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism ; Carcinoma, Ductal, Breast/*metabolism ; Cytochrome P-450 CYP2E1/*metabolism ; Female ; Humans ; Immunohistochemistry ; Menopause ; Middle Aged ; Receptors, Estrogen/analysis ; }, abstract = {Environmental chemicals are one of the risk factors in breast cancer genesis. Cytochrome P450 2E1 (CYP2E1), a member of multigene superfamily of enzymes, plays a major role in the activation of some of these chemicals such as tobacco-derived N-nitrosamines. Using immunohistochemistry, the cellular distribution and the level of expression of CYP2E1 was assessed in breast tumour and surrounding tumour free (control) breast tissue in 25 pairs of samples obtained from females with infiltrating ductal carcinoma. Cells staining with the CYP2E1 antibody showed only cytoplasmic positivity with varying intensities in 100% (25/25) of tumours and 96% (24/25) of normal breast tissues. Cytoplasmic staining was present in invasive ductal carcinoma cells but not in tumour stroma. CYP2E1 was detected in normal epithelial, myoepithelial and to a lesser degree in some of the non-epithelial cells (e.g. endothelial cells). No positive staining was detected in other non-epithelial cells such as fibroblasts in normal breast tissues. When CYP2E1 staining was assessed semiquantitatively the mean staining score values of CYP2E1 was found to be significantly higher in tumours compared to that of normal breast tissues. These results show that CYP2E1 protein is expressed in both tumour and normal breast tissue with an increased expression in breast tumours.}, } @article {pmid12847261, year = {2003}, author = {Tinsley, KW and Grayson, MH and Swanson, PE and Drewry, AM and Chang, KC and Karl, IE and Hotchkiss, RS}, title = {Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {171}, number = {2}, pages = {909-914}, doi = {10.4049/jimmunol.171.2.909}, pmid = {12847261}, issn = {0022-1767}, support = {GM44118/GM/NIGMS NIH HHS/United States ; GM55194/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*immunology ; B-Lymphocyte Subsets/chemistry/immunology ; Caspase 3 ; Caspases/physiology ; Cecum ; Cell Count ; Dendritic Cells, Follicular/enzymology/immunology/*pathology ; Disease Models, Animal ; Immunocompromised Host/immunology ; Immunohistochemistry ; Ligation ; Macrophages/chemistry/immunology ; Mice ; Mice, Inbred C57BL ; Punctures ; Sepsis/*immunology/*pathology ; Spleen/chemistry/enzymology/*immunology/*pathology ; Staining and Labeling ; T-Lymphocyte Subsets/chemistry/immunology ; }, abstract = {Dendritic cells are a phenotypically diverse group of APC that have unique capabilities to regulate the activity and survival of B and T cells. Although proper function of dendritic cells is essential to host control of invading pathogens, few studies have examined the impact of sepsis on dendritic cells. The purpose of this study was to determine the effect of sepsis on splenic interdigitating dendritic cells (IDCs) and follicular dendritic cells (FDCs) using a clinically relevant animal model. Immunohistochemical staining for FDCs showed that sepsis induced an initial marked expansion in FDCs that peaked at 36 h after onset. The FDCs expanded to fill the entire lymphoid zone otherwise occupied by B cells. Between 36 and 48 h after sepsis, there was a profound caspase 3 mediated apoptosis induced depletion of FDCs such that only a small contingent of cells remained. In contrast to the initial increase in FDCs, IDC numbers were decreased to approximately 50% of control by 12 h after onset of sepsis. IDC death occurred by caspase 3-mediated apoptosis. Such profound apoptosis induced loss of FDCs and IDCs may significantly compromise B and T cell function and impair the ability of the host to survive sepsis.}, } @article {pmid12846866, year = {2003}, author = {Gupta, D and Nath, M and Layfield, LJ}, title = {Utility of four-quadrant random sections in mastectomy specimens.}, journal = {The breast journal}, volume = {9}, number = {4}, pages = {307-311}, doi = {10.1046/j.1524-4741.2003.09411.x}, pmid = {12846866}, issn = {1075-122X}, mesh = {Biopsy/methods/*standards ; Breast Neoplasms/diagnostic imaging/*epidemiology/*pathology/surgery ; Carcinoma in Situ/epidemiology/pathology ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/pathology ; Carcinoma, Lobular/epidemiology/pathology ; Female ; Humans ; Incidence ; Mastectomy/methods ; Medical Records ; Pennsylvania/epidemiology ; Predictive Value of Tests ; Radiography ; Retrospective Studies ; Utah/epidemiology ; }, abstract = {Standard practice in surgical pathology dictates that random sections from the four quadrants of the breast be taken in mastectomy specimens. These sections are obtained in addition to sampling of any grossly visible lesions within the breast specimen. While tradition dictates the submission of these sections, we are unaware of any study supporting their efficacy. We have investigated the utility and significance of these random sections in a series of 78 mastectomy specimens. This retrospective study identified mastectomy specimens from pathology files of Magee Woman's Hospital, the University of Pittsburgh, and the University of Utah School of Medicine between 1997 and 2000. Clinical data (palpable versus nonpalpable), radiographic features (mammographic diagnosis, presence of mass density and/or calcification), and pathologic features (size, histopathologic type, etc.) were studied. The histologic sections of the cases were reviewed and the random sections were specifically studied for pathologic findings. Diagnosis and clinically significant features obtained from examining these random sections, but not demonstrable in grossly selected sections, were tabulated. A total of 78 mastectomy specimens were analyzed. Diagnoses rendered were infiltrating ductal carcinoma (23), infiltrating ductal carcinoma with ductal carcinoma in situ (DCIS) (16), DCIS (25), infiltrating lobular carcinoma (4), biopsy cavity with no residual malignancy (4), infiltrating lobular carcinoma with lobular carcinoma in situ (3), invasive ductal and lobular carcinoma (1), adenoid cystic carcinoma (1), and atypical ductal hyperplasia (1). The number of random sections ranged from 2 to 17 (mean 9). Random sections provided additional information in 21 of 78 mastectomies (27%). The multifocal/multicentric nature of the lesion was diagnosed in 20 cases: DCIS (6), lobular carcinoma in situ and invasive (2), invasive ductal carcinoma (6), invasive and in situ ductal carcinoma (5), invasive lobular carcinoma (1), invasive ductal and lobular carcinoma (1). Additional findings include lymphovascular invasion (2 cases), atypical ductal hyperplasia (1), DCIS at the operative margin (1), DCIS within less than 1 mm of an operative margin (1), and atypical lobular hyperplasia (1). In the remaining 57 cases, random sections did not provide any additional information. Histologic examination of random sections from breast quadrants yielded important information about the presence of multifocality, multicentricity, vascular invasion, and margin involvement by carcinoma in only a minority of cases, many of which had a lobular morphology.}, } @article {pmid12846864, year = {2003}, author = {Cabral, AH and Recine, M and Paramo, JC and McPhee, MM and Poppiti, R and Mesko, TW}, title = {Tubular carcinoma of the breast: an institutional experience and review of the literature.}, journal = {The breast journal}, volume = {9}, number = {4}, pages = {298-301}, doi = {10.1046/j.1524-4741.2003.09409.x}, pmid = {12846864}, issn = {1075-122X}, mesh = {Adenocarcinoma/*epidemiology/etiology/mortality/pathology/therapy ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/etiology/mortality/pathology/therapy ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Florida/epidemiology ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/*epidemiology/etiology/mortality/pathology/therapy ; Neoplasm Staging ; Receptors, Estrogen ; Retrospective Studies ; Survival Analysis ; }, abstract = {Tubular carcinoma of the breast is a variant of invasive ductal carcinoma that is well differentiated and characterized by an orderly tubular formation. Although often perceived to have a better prognosis, there continues to be questions regarding the extent of treatment required. A retrospective review of 44 patients diagnosed with tubular carcinoma of the breast from 1987 to 1999 was performed. All documented data regarding patient and tumor characteristics plus the extent of treatment were analyzed and compared. Lymph node metastases were present in 4 of 32 patients (13%) who had nodes examined. Tumor size correlated with axillary status, with tumors less than 15 mm having no axillary nodal involvement. No other factor influenced nodal status. In breast conservation patients without adjuvant radiation, 5% (1 of 20) had local recurrence versus 0% (0 of 13) of patients who received postoperative radiation. Ductal carcinoma in situ (DCIS) was associated with 52% of tubular cancers. Second breast cancers developed in 16% of cases. There was no difference in presentation or outcome for pure versus mixed tubular carcinoma. Overall mortality was 2%. Overall survival for patients with tubular carcinoma is quite good. Breast conservation treatment results in low rates of local recurrence for tubular carcinoma with or without the use of adjuvant radiation therapy. Pure tubular carcinomas had the same behavior and overall prognosis as mixed tubular carcinomas and should be classified together. Lymph node status did not influence disease-free or overall survival.}, } @article {pmid12845646, year = {2003}, author = {Buttiglieri, S and Galetto, A and Forno, S and De Andrea, M and Matera, L}, title = {Influence of drug-induced apoptotic death on processing and presentation of tumor antigens by dendritic cells.}, journal = {International journal of cancer}, volume = {106}, number = {4}, pages = {516-520}, doi = {10.1002/ijc.11243}, pmid = {12845646}, issn = {0020-7136}, mesh = {Annexin A5/metabolism ; Antigen Presentation/*physiology ; Antigens, Neoplasm/*immunology ; Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Cisplatin/pharmacology ; Cytokines/metabolism ; Dendritic Cells/*immunology ; Doxorubicin/pharmacology ; Epirubicin/pharmacology ; HSP70 Heat-Shock Proteins/metabolism ; Histocompatibility Antigens Class I/immunology ; Humans ; Necrosis ; Phagocytosis/drug effects ; Propidium/metabolism ; Stomach Neoplasms/*pathology ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Cells, Cultured ; }, abstract = {Here we have studied the effects of apoptotic cell death induced by chemotherapic agents on tumor phagocytosis by dendritic cells (DC) and presentation of the relevant antigen to T lymphocytes. Annexin-V-FITC (Ann-V) and propidium iodide (PI) staining was used to assess early apoptotic (Ann-V(+)/PI(-)) vs. late apoptotic/secondary necrotic (Ann-V(+)/PI(+)) death after a 24 hr observation of untreated and drug-treated gastric carcinoma cells. After treatments, the HLA-A*0201(+) tumor cell line KATO III was exposed for 24 hr to allogeneic, HLA-related GM-CSF, IL-4-driven immature (i) DC. Tumor-loaded iDC were tested for IL-12 release in an ELISA assay, incubated with the DC-maturating factor TNF-alpha and used as stimulators for autologous T lymphocytes. Generation of antitumor T response against KATO cells was evaluated in an anti-MHC class I MAb-blocked Interferon-gamma ELISPOT assay. After treatment with Cis-platin (cis), all dying cells were in early apoptosis, whereas secondary necrosis was the prevalent death pattern observed after epirubicin (epi) and doxorubicin (doxo). Doxo and epi increased tumor expression of heat shock protein (hsp) 70 and uptake of tumor cell components by DC, whereas cis treatment had no effect on hsp70 and was associated with poor tumor uptake by DC. Significant upmodulation of IL-12 was observed by DC that had taken up the doxo- and epi-treated tumors (p< 0.005 and p< 0.01, respectively). Increased IFN-gamma release was also observed after stimulation of T lymphocytes with DC loaded with doxo- and epi-treated (p< 0.02 and p< 0.005, respectively) but not with cis-treated DC. These data show that the products of early apoptosis cannot efficiently cross-activate MHC class I-restricted anti-tumor lymphocytes even in the presence of DC maturating factors, whereas secondary necrosis is associated with robust T cell response.}, } @article {pmid12841678, year = {2003}, author = {Dendale, R and Vincent-Salomon, A and Mouret-Fourme, E and Savignoni, A and Medioni, J and Campana, F and Vilcoq, JR and de la Rochefordière, A and Soussi, T and Asselain, B and de Cremoux, P and Fourquet, A}, title = {Medullary breast carcinoma: prognostic implications of p53 expression.}, journal = {The International journal of biological markers}, volume = {18}, number = {2}, pages = {99-105}, doi = {10.5301/jbm.2008.1279}, pmid = {12841678}, issn = {0393-6155}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/genetics/mortality ; Carcinoma, Medullary/*chemistry/genetics/mortality ; Female ; Genes, p53 ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.}, } @article {pmid12840971, year = {2003}, author = {Kanibolotskiĭ, AA and Lun'kova, LK and Makarova, OV and Solokhin, EV and Potemkin, AM and Mitkova, SV}, title = {[Prevalence and postmortem diagnosis of hemocontact infections in intravenous drug abusers based on forensic medical research data].}, journal = {Sudebno-meditsinskaia ekspertiza}, volume = {46}, number = {3}, pages = {14-16}, pmid = {12840971}, issn = {0039-4521}, mesh = {Autopsy ; *Forensic Medicine ; HIV Infections/*complications/diagnosis ; Hepatitis B/*complications/diagnosis ; Hepatitis C/*complications/diagnosis ; Humans ; Immunoenzyme Techniques ; Prevalence ; Substance Abuse, Intravenous/*complications ; }, abstract = {The spread of viral hepatitis C and B and of HIV was studied among the intravenous drug consumers (IDC) on the basis of 42 forensic-medical autopsies. The enzyme immune-assay (EIA) of blood serum showed, in 95.2% of cases, antibodies to hepatitis C virus, antibodies to HbsAg and HIV were registered in 11.9% in both cases. The possibilities of using the autopsy-blood serum for EIA-diagnosis of viral hepatitis and HIV were demonstrated. Morphological examinations of IDC showed, in them, chronic hepatitis (CH) of minimal, weakly-pronounced and moderate activities. Viral CH in HIV infected IDCs is characterized by a minimal and small-pronounced activity of the process and it is not different, according to its activity, from viral CH in IDCs without HIV.}, } @article {pmid12835955, year = {2003}, author = {Becker, R and Haass, M and Ick, D and Krueger, C and Bauer, A and Senges-Becker, JC and Voss, F and Hilbel, T and Niroomand, F and Katus, HA and Schoels, W}, title = {Role of nonsustained ventricular tachycardia and programmed ventricular stimulation for risk stratification in patients with idiopathic dilated cardiomyopathy.}, journal = {Basic research in cardiology}, volume = {98}, number = {4}, pages = {259-266}, doi = {10.1007/s00395-003-0398-7}, pmid = {12835955}, issn = {0300-8428}, mesh = {Adult ; Cardiomyopathy, Dilated/*mortality ; Disease-Free Survival ; Electrocardiography, Ambulatory ; Electrophysiologic Techniques, Cardiac ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; *Pacemaker, Artificial ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Risk Factors ; Tachycardia, Ventricular/*diagnosis/*mortality ; }, abstract = {BACKGROUND: The prognostic role of asymptomatic nonsustained ventricular tachycardia (NSVT) and programmed ventricular stimulation (PVS) in patients with idiopathic dilated cardiomyopathy (IDC) remains controversial.

METHODS: The prognostic significance of ventricular arrhythmias, ejection fraction, NYHA class, atrial fibrillation and age for overall and sudden death mortality was prospectively studied in 157 patients with IDC (group 1) free of documented sustained ventricular arrhythmia and syncope. In 99 patients with asymptomatic NSVT (group 2), PVS with 2 - 3 extrastimuli was performed. Non-inducible patients were discharged without specific antiarrhythmic therapy, whereas those with inducible monomorphic ventricular tachycardia were implanted with an ICD.

RESULTS: In group 1, 48% of patients had NSVT. Overall and sudden death mortality were significantly higher in patients with NSVT (34.2 vs. 9.8%, p = 0.0001 and 15.8 vs. 3.7%, p = 0.0037; follow-up 22 +/- 14 months). Multivariate analysis revealed that NSVT independently predicts both overall and sudden death mortality (p = 0.0021 and.0221, respectively; adjusted for EF, NYHA class and age). In group 2, inducibility of sustained ventricular tachyarrhythmia was 7%, but sustained monomorphic VT occurred in 3% only. Two of 7 inducible patients experienced arrhythmic events during a follow-up of 25 +/- 21 months (positive predictive value 29%). Overall and sudden death mortality were 29% and 0% in the inducible group vs. 17 and 4% in the non-inducible group. Both overall and sudden death mortality were significantly lower in non-inducible patients from group 2 as compared to patients from group 1 with NSVT (p = 0.0043 and 0.0048), most likely due to a more common use of betablockers and a higher EF in the former group (p < 0.001, respectively).

CONCLUSIONS: In patients with IDC, NSVT independently predicts both overall and sudden death mortality. Due to a low inducibility rate and a poor positive predictive value, PVS seems inappropriate for further arrhythmia risk assessment. However, in spite of documented NSVT, the incidence of SCD in patients on optimized medical treatment including betablockers seems to be very low, questioning the need for specific arrhythmia risk stratification.}, } @article {pmid12835515, year = {2003}, author = {Tagawa, Y and Yasutake, T and Ikuta, Y and Oka, T and Terada, R}, title = {Chromosome 8 numerical aberrations in stage II invasive ductal carcinoma: correlation with patient outcome and poor prognosis.}, journal = {Medical oncology (Northwood, London, England)}, volume = {20}, number = {2}, pages = {127-136}, pmid = {12835515}, issn = {1357-0560}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal/*genetics/pathology ; *Chromosome Aberrations ; *Chromosomes, Human, Pair 8 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Staging ; Prognosis ; Survival Analysis ; }, abstract = {Aberrations in chromosome 8 are common in breast cancer. However, the relationship between numerical aberrations of chromosome 8 and clinical behavior (especially prognosis) in breast cancer is not well understood. In this study, a total of 40 specimens of stage II invasive ductal carcinomas (IDCs) was analyzed by fluorescence in situ hybridization (FISH) with a chromosome 8 centromere-specific probe and DNA flow cytometry (stage IIA: 20 cases; stage IIB: 20 cases). All cases were followed for at least 5.7 yr (mean: 7.5 yr; median: 7.7 yr) after surgery or until death. Single (loss), double, and triple or more signals (gain) of chromosome 8 were found in 7.6 +/- 3.5% (range: 2-16%; median: 7%), 53.7 +/- 13.2% (range: 25-81%, median: 53%), and 38.7 +/- 13.2% (range: 17-65%, median: 38%), respectively, of tumors. The frequencies of chromosome 8 gain and disomy correlated with patient outcome (respectively p < 0.05 and p < 0.01). When median ratios of chromosome 8 loss, disomy, and gain were used as the cutoff values, the survival curves revealed that patients in the low-frequency group survived significantly longer than those in the high-frequency group for chromosome 8 gain (p < 0.05), and patients in the high-frequency group survived significantly longer than those in the low-frequency group for chromosome 8 disomy (p < 0.05). Poor prognosis was not associated with age, tumor size, lymph node metastasis, histologic type, TNM stage, estrogen-receptor status, progesterone- receptor status, or DNA ploidy. Our results suggest that the frequencies of chromosome 8 gain and disomy is a potentially useful parameter for predicting prognosis of stage II IDCs.}, } @article {pmid12834769, year = {2003}, author = {Bakkali, H and Marchal, C and Lesur-Schwander, A and Verhaeghe, JL}, title = {[Breast cancer in women thirty years old or less].}, journal = {Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique}, volume = {7}, number = {3}, pages = {153-159}, doi = {10.1016/s1278-3218(03)00021-0}, pmid = {12834769}, issn = {1278-3218}, mesh = {Adult ; Age Distribution ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/diagnosis/*epidemiology/etiology/therapy ; Carcinoma, Ductal, Breast/epidemiology ; Combined Modality Therapy ; Female ; France/epidemiology ; Genetic Predisposition to Disease/genetics ; Humans ; Lymph Node Excision ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Palpation ; Patient Selection ; Prognosis ; Receptors, Estrogen ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome ; }, abstract = {PURPOSE: Breast cancer rarely occurs in very young women, its diagnosis and management could sometimes be difficult. Our aim is to analyse the epidemiological and clinicopathological features of a group of very young women and especially to evaluate the results of therapeutic strategy.

METHODS: We report a retrospective study conducted at the department of radiotherapy in Alexis-Vautrin Centre, concerning 30 patients aged < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between 1986 and 2001.

RESULTS: Six patients had familial history of breast cancer. Palpable tumor was found in 90% of cases, the average size was 3.5 cm. Eleven patients presented with stage I, 11 presented with stage II, 6 presented with stage III and 2 presented with stage IV. Five cancers were diagnosed after pregnancy (average tumor size = 5.8 cm). Eleven patients received neoadjuvant chemotherapy and 23 (82%) of 28 operable cases of invasive malignancy underwent breast conservative surgery (BCS). We found an invasive ductal carcinoma with grade III in 13/27 cases and a nodal involvement in a half of cases, 11 patients of 26 had no expression of oestrogen receptor. The average follow-up was 5 years: six patients (20%) recurred locally (all of them were initially treated by BCS), four patients developed a contralateral breast cancer and three developed a second malignancy. Ten patients died of their metastatic disease. The 5-year overall survival rate was 78%.

CONCLUSION: Our results are consistent with those of the published reports and suggest that very young women with breast cancer have a poorer prognosis compared with the older ones. They should receive, according to their prognostic factors, an appropriate regional, systemic and hormonal therapy.}, } @article {pmid12832972, year = {2003}, author = {Ishikawa, O and Wada, H and Ohigashi, H and Doki, Y and Yokoyama, S and Noura, S and Yamada, T and Sasaki, Y and Imaoka, S and Kasugai, T and Matsunaga, T and Takenaka, A and Nakaizumi, A}, title = {Postoperative cytology for drained fluid from the pancreatic bed after "curative" resection of pancreatic cancers: does it predict both the patient's prognosis and the site of cancer recurrence?.}, journal = {Annals of surgery}, volume = {238}, number = {1}, pages = {103-110}, pmid = {12832972}, issn = {0003-4932}, mesh = {Adenocarcinoma/*pathology/surgery ; Adult ; Aged ; Ascitic Fluid/*cytology ; Drainage ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Neoplasm, Residual/*pathology ; Pancreatectomy/*methods ; Pancreatic Neoplasms/*pathology/surgery ; *Peritoneal Lavage ; Postoperative Care ; Predictive Value of Tests ; Prognosis ; }, abstract = {OBJECTIVE: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer.

SUMMARY BACKGROUND DATA: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy.

METHODS: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence.

RESULTS: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence.

CONCLUSIONS: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.}, } @article {pmid12824875, year = {2003}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Tumor cells in lymph vessels and lymph nodes closely associated with nodal metastasis by invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {94}, number = {6}, pages = {508-514}, doi = {10.1111/j.1349-7006.2003.tb01474.x}, pmid = {12824875}, issn = {1347-9032}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/*secondary/therapy ; Disease Progression ; Female ; Humans ; Japan ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Lymphatic Vessel Tumors/*secondary ; Lymphatic Vessels/pathology ; Menopause ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; }, abstract = {No studies have ever precisely investigated the mechanism of nodal metastasis based on the histological characteristics of tumor cells in lymph vessels and lymph nodes. The purpose of this study was to investigate whether the histological characteristics of tumor cells in lymph vessels and lymph nodes of 393 patients with invasive ductal carcinoma (IDC) were significantly associated with increased nodal metastasis compared with well known histological characteristics of their primary-invasive tumor cells. Multivariate analyses showed that having a single nodal metastasis was closely dependent on primary-invasive tumor size or distance of lymph vessel tumor emboli from the margin of the primary-invasive tumor (P < 0.05) and that having 2 or more nodal metastases was significantly associated with the histological characteristics of the nodal metastatic tumors independently of the size of the primary-invasive tumor, and the number of nodes with extra-nodal invasion (ENI) significantly increased the relative risk (RR) of 4 or more nodal metastases in IDCs 20 to 50 mm in size, number of lymph vessels invaded, severe fibrosis of the stroma of extra-nodal invasive tumors, and distance of ENI from the node significantly increased the RR of 10 or more nodal metastases in the multivariate analysis (P < 0.05). The results of this study strongly suggest that the histological characteristics of tumor cells in lymph nodes and lymph vessels play an important role in nodal metastasis in IDCs of the breast.}, } @article {pmid12824206, year = {2003}, author = {Li, CI and Malone, KE and Porter, PL and Weiss, NS and Tang, MT and Cushing-Haugen, KL and Daling, JR}, title = {Relationship between long durations and different regimens of hormone therapy and risk of breast cancer.}, journal = {JAMA}, volume = {289}, number = {24}, pages = {3254-3263}, doi = {10.1001/jama.289.24.3254}, pmid = {12824206}, issn = {1538-3598}, support = {R01 CA072787/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Breast Neoplasms/*epidemiology/metabolism/pathology ; Carcinoma, Ductal, Breast/epidemiology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology ; Carcinoma, Lobular/epidemiology ; Case-Control Studies ; Drug Administration Schedule ; *Estrogen Replacement Therapy/adverse effects ; Estrogens/*therapeutic use ; Female ; Humans ; Logistic Models ; Progestins/*therapeutic use ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk ; SEER Program ; Time Factors ; Washington/epidemiology ; }, abstract = {CONTEXT: Women using combined estrogen and progestin hormone replacement therapy (CHRT) have an increased risk of breast cancer; however, data on use for long durations and on risk associated with patterns of use are lacking.

OBJECTIVE: To evaluate relationships between durations and patterns of CHRT use and risk of breast cancer by histological type and hormone receptor status.

DESIGN: Population-based case-control study.

SETTING: Three counties in western Washington State.

PARTICIPANTS: Nine hundred seventy-five women 65-79 years of age diagnosed with invasive breast cancer from April 1, 1997, through May 31, 1999 (histology: 196 lobular cases, 656 ductal cases, 114 cases with other histological type, and 9 cases with an unspecified histological type; estrogen receptor (ER)/progesterone receptor (PR) status: 646 ER+/PR+ cases, 147 ER+/PR- cases, and 101 ER-/PR- cases [6 ER-/PR+ cases and 75 cases with unknown ER/PR status were not included in the analyses herein]) and 1007 population controls.

MAIN OUTCOME MEASURES: Risks of invasive lobular, ductal, ER+/PR+, ER+/PR-, and ER-/PR- breast carcinomas.

RESULTS: Women using unopposed estrogen replacement therapy (ERT) (exclusive ERT use), even for 25 years or longer, had no appreciable increase in risk of breast cancer, although the associated odds ratios were not inconsistent with a possible small effect. Ever users of CHRT (includes CHRT users who also had used ERT) had a 1.7-fold (95% confidence interval [CI], 1.3-2.2) increased risk of breast cancer, including a 2.7-fold (95% CI, 1.7-4.3) increased risk of invasive lobular carcinoma, a 1.5-fold (95% CI, 1.1-2.0) increased risk of invasive ductal carcinoma, and a 2.0-fold (95% CI, 1.5-2.7) increased risk of ER+/PR+ breast cancers. The increase in risk was greatest in those using CHRT for longer durations (users for 5-14.9 years and >or=15 years had 1.5-fold [95% CI, 1.0-2.3] and 1.6-fold [95% CI, 1.0-2.6] increases in risk of invasive ductal carcinoma, respectively, and 3.7-fold [95% CI, 2.0-6.6] and 2.6-fold [95% CI, 1.3-5.3] increases in risk of invasive lobular carcinoma, respectively. Associations of similar magnitudes were seen among users of both sequential and continuous CHRT. Risks of ER+/PR- and ER-/PR- tumors were not increased by use of any form of hormone replacement therapy; however, small numbers of these tumors limited power to detect possible associations.

CONCLUSION: These data suggest that use of CHRT is associated with an increased risk of breast cancer, particularly invasive lobular tumors, whether the progestin component was taken in a sequential or in a continuous manner.}, } @article {pmid12822446, year = {2003}, author = {Tozaki, M and Fukuda, Y and Fukuda, K}, title = {[Multi-section magnetic susceptibility perfusion echo-planar imaging of the breast].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {63}, number = {5}, pages = {214-220}, pmid = {12822446}, issn = {0048-0428}, mesh = {Adult ; Aged ; Breast/pathology ; Breast Neoplasms/*diagnosis/pathology ; Diagnosis, Differential ; Echo-Planar Imaging/*methods ; Female ; Humans ; Middle Aged ; }, abstract = {PURPOSE: To examine the diagnostic value of multi-section magnetic susceptibility perfusion echo-planar imaging (perfusion EPI) in patients with breast tumors prior to T1-weighted dynamic MRI.

MATERIALS AND METHODS: MR imaging was performed in 75 patients with pathologically proved breast tumors using a 1.5 Tesla MR unit (MAGNETOM Symphony, Siemens Medical Solutions, Erlangen, Germany). Perfusion EPI was carried out before, during, and after the bolus injection of 0.1 mmol Gd-DTPA/kg. Two patients had two carcinomas in the same breast, one patient had both a benign and a malignant lesion in the same breast, and two patients had lesions in both breasts. Histopathological diagnosis was non-invasive ductal carcinoma in 9, invasive carcinoma in 49, and benign lesion in 22. The first-pass signal intensity loss of the lesions was calculated by perfusion EPI.

RESULTS: Fifty-one of 58 carcinomas but only 4 of 22 benign lesions had a signal intensity loss of 20% or more during the first pass, for a sensitivity of 88% and specificity of 82%

CONCLUSION: Perfusion EPI can be used as a useful diagnostic tool for differentiation between benign and malignant lesions. It is also thought to be a promising method for diagnosing multifocal breast lesions.}, } @article {pmid12817473, year = {2003}, author = {Wenzel, K and Felix, SB and Flachmeier, C and Heere, P and Schulze, W and Grunewald, I and Pankow, H and Hewelt, A and Scherneck, S and Bauer, D and Hoehe, MR}, title = {Identification and characterization of KAT, a novel gene preferentially expressed in several human cancer cell lines.}, journal = {Biological chemistry}, volume = {384}, number = {5}, pages = {763-775}, doi = {10.1515/BC.2003.085}, pmid = {12817473}, issn = {1431-6730}, mesh = {Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Carcinoma, Ductal, Breast/metabolism ; Cell Adhesion Molecules/genetics ; Cell Line, Tumor ; Chromosomes, Human, Pair 1/*genetics ; *DNA-Binding Proteins ; Gene Frequency ; Genes ; Humans ; Molecular Sequence Data ; Neoplasm Proteins/biosynthesis/*genetics ; Neoplasms/*genetics/metabolism ; Nuclear Envelope/metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Cell Surface/genetics ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Transcription Factors/genetics ; Transcription Initiation Site ; Upstream Stimulatory Factors ; }, abstract = {We describe the molecular characterization of a novel human gene on chromosome 1q23.3, termed KAT, which is highly conserved among mammals. The KAT gene spans a genomic region of approximately 1.6 kilobases and consists of 4 exons encoding a 115 amino acid protein with a molecular mass of about 12.5 kDa. The gene is expressed in several human tissues, including kidney, liver, skeletal muscle, heart, colon, thymus, spleen, placenta and lung. We identified an alternatively spliced form, lacking exon 2, in human and mouse tissues. In silico analysis of expressed sequence tags, derived from different types of human tumors, revealed another splice variant. This transcript is characterized by retention of the third intron, leading to a truncated translation product. The KAT protein is localized around the nuclear membranes. It was found to be expressed in several breast, colon and lung carcinoma cell lines, but not in normal breast epithelial cell lines. In addition, KAT protein was detected in invasive ductal carcinoma, but not in adjacent tissues. This suggests a role of this gene in tumorigenesis.}, } @article {pmid12800791, year = {2003}, author = {Crawford, ED}, title = {A 42-year-old woman with breast cancer.}, journal = {Oncology (Williston Park, N.Y.)}, volume = {17}, number = {5}, pages = {614; discussion 615-20}, pmid = {12800791}, issn = {0890-9091}, mesh = {Adult ; Antineoplastic Agents, Hormonal/administration & dosage ; Biopsy, Needle ; Breast Neoplasms/*pathology/*therapy ; Carcinoma, Ductal, Breast/*pathology/*therapy ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes/*pathology/surgery ; Mammography ; Mastectomy, Segmental ; Premenopause ; Prognosis ; Radiotherapy, Adjuvant ; Receptors, Estrogen/analysis ; *Referral and Consultation ; Risk Assessment ; Sentinel Lymph Node Biopsy ; Tamoxifen/administration & dosage ; Treatment Outcome ; }, abstract = {This premenopausal women has a T1c, N1 (two nodes positive) ER-positive, PR weakly positive, HER2 FISH-positive, grade 3 invasive ductal carcinoma. She has been treated with lumpectomy and axillary node dissection. The recommendation of the panel is for her to join one of the randomized trials studying the role of trastuzumab in node-positive breast cancers. Off protocol, we would recommend adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by docetaxel, although numerous options are available. Chemotherapy would be followed by radiation therapy and hormonal treatment. At this point, we recommend tamoxifen, with consideration to adding goserelin (Zoladex) if the patient does not remain amenorrheic. The patient chose to enter the Intergroup trastuzumab trial.}, } @article {pmid12795749, year = {2003}, author = {Mario, FD and Dal Bo, N and Aragona, G and Moussa, AM and Iori, V and Cavestro, GM and Pilotto, A and Leandro, G and Franceschi, M and Rugge, M and Franze, A}, title = {Rabeprazole in a one-week eradication therapy of Helicobacter pylori: comparison of different dosages.}, journal = {Journal of gastroenterology and hepatology}, volume = {18}, number = {7}, pages = {783-786}, doi = {10.1046/j.1440-1746.2003.03035.x}, pmid = {12795749}, issn = {0815-9319}, mesh = {2-Pyridinylmethylsulfinylbenzimidazoles ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/*administration & dosage ; Antitrichomonal Agents/administration & dosage ; Benzimidazoles/*administration & dosage ; Breath Tests ; Clarithromycin/administration & dosage ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Omeprazole/analogs & derivatives ; Rabeprazole ; Tinidazole/administration & dosage ; Treatment Outcome ; }, abstract = {AIM: Many data regarding omeprazole-, lanzoprazole- and pantoprazole-based triple therapy for Helicobacter pylori (H. pylori) eradication have been reported, but there is few data present regarding rabeprazole (R). We report the efficacy and tolerability of rabeprazole in different dosages in association with clarithromycin (C)and tinidazole (T) in H. pylori eradication.

DESIGN AND METHODS: Ninety-four H. pylori-positive patients with dyspeptic symptoms were enrolled and randomly allocated to eradication therapy in two different one-week regimens. In regimen A, 47 patients received R 20 mg b.i.d, C 500 mg b.i.d and T 500 mg b.i.d, while in regimen B, 47 patients received R 10 mg b.i.d, C 500 mg b.i.d and T 500 mg b.i.d. Eradication of H. pylori was evaluated by a 13C urea breath test (UBT) two months after the end of the therapy.

RESULTS: Four patients (two in each regimen) did not complete treatment. The H. pylori eradication rate was 91.4% in group A compared to 89.3% in group B (P-value not significant). Minor side-effects were reported in 4.2% of group A and 6.4% of group B patients.

CONCLUSION: Rabeprazole showed good efficacy and tolerability in one-week H. pylori therapy at 20 mg b.i.d and 10 mg b.i.d, suggesting the use of the lower dosage.}, } @article {pmid12795089, year = {2003}, author = {Kuroi, K and Toi, M}, title = {[Male breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {30}, number = {5}, pages = {599-605}, pmid = {12795089}, issn = {0385-0684}, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/therapeutic use ; *Breast Neoplasms, Male/diagnosis/drug therapy/genetics ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Diagnosis, Differential ; Fluorouracil/administration & dosage ; Gynecomastia/diagnostic imaging ; Humans ; Male ; Mammography ; Methotrexate/administration & dosage ; Prognosis ; Ultrasonography, Mammary ; }, abstract = {As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.}, } @article {pmid12794169, year = {2003}, author = {De, AK and Laudanski, K and Miller-Graziano, CL}, title = {Failure of monocytes of trauma patients to convert to immature dendritic cells is related to preferential macrophage-colony-stimulating factor-driven macrophage differentiation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {12}, pages = {6355-6362}, doi = {10.4049/jimmunol.170.12.6355}, pmid = {12794169}, issn = {0022-1767}, support = {GM36214/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Antigen-Presenting Cells/immunology/metabolism/pathology ; Cell Differentiation/immunology ; Cells, Cultured ; Dendritic Cells/*immunology/metabolism/pathology ; Down-Regulation/immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-12/antagonists & inhibitors/biosynthesis ; Interleukin-4/pharmacology ; Isoantigens/immunology ; Lymphocyte Culture Test, Mixed ; Macrophage Colony-Stimulating Factor/*physiology ; Macrophages/*immunology/metabolism/pathology ; Male ; Middle Aged ; Monocytes/*immunology/metabolism/pathology ; T-Lymphocyte Subsets/immunology/metabolism ; Wounds and Injuries/*immunology/*pathology ; }, abstract = {Following trauma, increased inflammatory monokine activation and depressed APC function can occur simultaneously. These contradictory monocyte (Mphi) dysfunctions could result if postinjury Mphi differentiation preferentially favored inflammatory macrophage (Mac) differentiation over development into the most potent APC, dendritic cells (DC). In this report, Mphi of trauma patients with a depressed MLR induction capacity are, for the first time, shown to be unable to differentiate in vitro to immature CD1a(+) DC under the influence of GM-CSF and IL-4. Trauma patient Mphi that retained MLR-inducing capacity had a nonsignificant reduction in DC differentiation capacity. Only patient Mphi populations with depressed differentiation to immature DC (iDC) demonstrated depressed IL-12 and IL-15 production and a continued reduced MLR induction capacity. Neither increased IL-10 production nor decreased CD11c(+) DC precursor numbers correlated with depressed Mphi-to-DC differentiation. Instead, these patients' APC-dysfunctional Mphi populations had increased expression of inflammatory Mac phenotypes (CD64(+), CD86(low), HLA-DR(low)) and up-regulated secretion of M-CSF. M-CSF combined with IL-6 inhibits Mphi-to-iDC differentiation and promotes Mphi-to-Mac differentiation by down-regulating GM-CSFR expression and increasing DC apoptosis. Both depressed GM-CSFR expression and increased Mphi iDC apoptosis, as well as increased expression of CD126 (IL-6R) and CD115 (M-CSFR), were detected in APC-defective patient Mphi. In vitro addition of anti-M-CSF enhanced the IL-4 plus GM-CSF-induced Mphi-to-DC differentiation of these patients. This suggests that, in trauma patients, enhanced Mphi-to-Mac differentiation with concomitant inhibited iDC development is partially due to increased circulating Mphi sensitivity to and production of M-CSF and contributes to postinjury immunoaberrations.}, } @article {pmid12793903, year = {2003}, author = {Greenberg, R and Schwartz, I and Skornick, Y and Kaplan, O}, title = {Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary drainage after operations for breast cancer using reverse transcriptase-polymerase chain reaction.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {3}, pages = {R71-6}, pmid = {12793903}, issn = {1465-542X}, mesh = {Axilla/*pathology/surgery ; Biomarkers, Tumor/biosynthesis/genetics ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/secondary/surgery ; *Drainage ; Exudates and Transudates/chemistry ; Female ; Humans ; Lymph Nodes/pathology/surgery ; Lymphatic Metastasis/genetics/pathology ; Middle Aged ; Neoplasm Invasiveness/genetics/pathology ; Proto-Oncogene Proteins c-met/*biosynthesis/genetics ; RNA, Messenger/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; }, abstract = {BACKGROUND: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance.

METHODS: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status.

RESULTS: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02).

CONCLUSION: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.}, } @article {pmid12793894, year = {2003}, author = {Shirakawa, K and Kobayashi, H and Sobajima, J and Hashimoto, D and Shimizu, A and Wakasugi, H}, title = {Inflammatory breast cancer: vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model.}, journal = {Breast cancer research : BCR}, volume = {5}, number = {3}, pages = {136-139}, pmid = {12793894}, issn = {1465-542X}, mesh = {Animals ; Blood Vessels/pathology ; Breast Neoplasms/*blood supply/genetics/*pathology/ultrastructure ; Chromosome Aberrations ; Cytogenetic Analysis ; *Disease Models, Animal ; Endothelium, Vascular/*pathology/ultrastructure ; *Hemodynamics/genetics ; Humans ; Inflammation/genetics ; Magnetic Resonance Angiography ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Paraffin Embedding ; Time Factors ; Transplantation, Heterologous/*methods ; Tumor Cells, Cultured ; }, abstract = {We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, vasculogenic mimicry, which showed an absence of endothelial cells, was observed. Comparison of WIBC-9 with an established non-IBC xenograft (MC-5), using time-course dynamic micro-magnetic resonance angiography analysis (with a newly developed intravascular macromolecular contrast agent for magnetic resonance imaging) demonstrated that the WIBC-9 tumor had blood flow and a vascular mimicry-angiogenesis junction.}, } @article {pmid12792731, year = {2003}, author = {Kurosumi, M and Tabei, T and Inoue, K and Takei, H and Ninomiya, J and Naganuma, R and Suemasu, K and Higashi, Y and Tsuchiya, E}, title = {Prognostic significance of scoring system based on histological heterogeneity of invasive ductal carcinoma for node-negative breast cancer patients.}, journal = {Oncology reports}, volume = {10}, number = {4}, pages = {833-837}, pmid = {12792731}, issn = {1021-335X}, mesh = {Adenocarcinoma/classification/metabolism/pathology ; Adenocarcinoma, Papillary/classification/metabolism/pathology ; Adenocarcinoma, Scirrhous/classification/metabolism/pathology ; Adult ; Aged ; Breast Neoplasms/classification/metabolism/*pathology ; Carcinoma, Ductal, Breast/classification/metabolism/*pathology ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptors, Estrogen/metabolism ; Survival Rate ; }, abstract = {This study aimed to determine the prognostic significance of histological scoring system based on heterogeneity of invasive ductal carcinoma, for node-negative breast cancer patients. We studied 108 patients of node-negative invasive ductal carcinoma with invasive tumor >5 mm. Histological score of each patient was evaluated based on histological subtype of invasive ductal carcinoma and pattern of its heterogeneity. Score of each subtype was defined as follows; papillotubular carcinoma: score 1, solid-tubular carcinoma: score 2 and scirrhous carcinoma: score 3. The existence of histological heterogeneity was examined, and corresponding score was doubled in a pure case and scores of two dominant subtypes were summed in a composite case. Overall survival curves defined by sores were drawn by Kaplan-Meier method and the difference in survival rate was evaluated by log-rank test. The most significant difference of overall survival was recognized between low score group (scores 2, 3 and 4) and high score group (scores 5 and 6) (p<0.001). In addition, multivariate analysis confirmed that only histological score was an independent prognostic factor. These results suggested that assessment of histological heterogeneity of invasive ductal carcinoma could serve as independent potent prognostic factor for node-negative invasive ductal carcinoma of the breast, and this method might be useful to decide indication of postoperative adjuvant chemotherapy.}, } @article {pmid12792359, year = {2003}, author = {Woody, GE and Gallop, R and Luborsky, L and Blaine, J and Frank, A and Salloum, IM and Gastfriend, D and Crits-Christoph, P and , }, title = {HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative Treatment Study.}, journal = {Journal of acquired immune deficiency syndromes (1999)}, volume = {33}, number = {1}, pages = {82-87}, doi = {10.1097/00126334-200305010-00012}, pmid = {12792359}, issn = {1525-4135}, support = {P30-MH-45178/MH/NIMH NIH HHS/United States ; U01-DA07693/DA/NIDA NIH HHS/United States ; DA05593/DA/NIDA NIH HHS/United States ; K05-DA 00168/DA/NIDA NIH HHS/United States ; U01-DA07673/DA/NIDA NIH HHS/United States ; U01DA07090/DA/NIDA NIH HHS/United States ; U01-DA07663/DA/NIDA NIH HHS/United States ; K02-DA 00326/DA/NIDA NIH HHS/United States ; U01-DA07085/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Antisocial Personality Disorder ; Cocaine-Related Disorders/*complications/*therapy ; Female ; HIV Infections/*complications/etiology/*prevention & control/transmission ; Humans ; Male ; Middle Aged ; *National Institutes of Health (U.S.) ; Patient Dropouts ; Psychotherapy ; Racial Groups ; Risk Factors ; *Risk Reduction Behavior ; Safe Sex ; Sex Factors ; Sexual Behavior ; Treatment Refusal ; United States ; }, abstract = {HIV risk was evaluated among 487 cocaine-dependent patients recruited from five treatment programs in a trial that examined the efficacy of four outpatient-based psychosocial treatments. Treatments were offered two to three times per week for 6 months and consisted of group drug counseling (GDC) or group counseling plus individual drug counseling (IDC), cognitive therapy (CT), or supportive-expressive therapy (SE). The average patient had used cocaine for 7 years, with 10 days of use in the last month. Crack smoking was the main route in 79%, and HIV risk was mainly due to multiple partners and unprotected sex. Treatment was associated with a decrease in cocaine use from an average of 10 days per month at baseline to 1 day per month at 6 months. Reduction in cocaine use was associated with an average 40% decrease in HIV risk across all treatment, gender, and ethnic groups, mainly as a result of fewer sexual partners and less unprotected sex. The combination of IDC and GDC was associated with an equal or even greater reduction in HIV risk than the other treatment conditions and thus shows promise as an effective HIV prevention strategy, at least for some patients.}, } @article {pmid12792192, year = {2003}, author = {Kennedy, C and Charlesworth, A and Chen, JL}, title = {Interactive data collection: benefits of integrating new media into pediatric research.}, journal = {Computers, informatics, nursing : CIN}, volume = {21}, number = {3}, pages = {120-127}, doi = {10.1097/00024665-200305000-00007}, pmid = {12792192}, issn = {1538-2931}, support = {R01 NR004680-02/NR/NINR NIH HHS/United States ; }, mesh = {Child ; Computer Literacy ; Data Collection/*methods ; Humans ; Longitudinal Studies ; Microcomputers ; *Multimedia ; Nursing Assessment/*methods ; Nursing Research/*methods ; *Pediatric Nursing ; *Software Design ; Software Validation ; *User-Computer Interface ; Video Games ; }, abstract = {Despite the prevalence of children's computerized games for recreational and educational purposes, the use of interactive technology to obtain pediatric research data remains underexplored. This article describes the development of laptop interactive data collection (IDC) software for a children's health intervention study. The IDC integrates computer technology, children's developmental needs, and quantitative research methods that are engaging for school-age children as well as reliable and efficient for the pediatric health researcher. Using this methodology, researchers can address common problems such as maintaining a child's attention throughout an assessment session while potentially increasing their response rate and reducing missing data rates. The IDC also promises to produce more reliable data by eliminating the need for manual double entry of data and reducing much of the time and costs associated with data cleaning and management. Development and design considerations and recommendations for further use are discussed.}, } @article {pmid12786889, year = {2003}, author = {Umekita, Y and Yoshida, H}, title = {Expression of maspin is up-regulated during the progression of mammary ductal carcinoma.}, journal = {Histopathology}, volume = {42}, number = {6}, pages = {541-545}, doi = {10.1046/j.1365-2559.2003.01620.x}, pmid = {12786889}, issn = {0309-0167}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*metabolism/secondary ; Disease Progression ; Female ; Fluorescent Antibody Technique, Indirect ; *Genes, Tumor Suppressor ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis ; Proteins/analysis/genetics/*metabolism ; Serpins/analysis/genetics/*metabolism ; Up-Regulation ; }, abstract = {AIMS: The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down-regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS).

METHODS AND RESULTS: To clarify whether there is down-regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative.

CONCLUSIONS: These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up-regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.}, } @article {pmid12785176, year = {2002}, author = {Das, BR and Kundu, B and Khandapkar, R and Sahni, S}, title = {Geographical distribution of hepatitis C virus genotypes in India.}, journal = {Indian journal of pathology & microbiology}, volume = {45}, number = {3}, pages = {323-328}, pmid = {12785176}, issn = {0377-4929}, mesh = {*Genotype ; Hepacivirus/classification/*genetics/physiology ; Hepatitis C/diagnosis/epidemiology/*virology ; India/epidemiology ; RNA, Viral/genetics ; }, abstract = {HCV isolates from around the world show substantial nucleotide sequence variability throughout the viral genome. Based on the identification of these genome differences various genotypes and subtypes have been described from different geographical regions. They have been tentatively classified into six major genotypes and more than 30 subtypes, but new subtypes are continually being discovered. In recent years, substantial evidence has emerged indicating that typing and subtyping for HCV is clinically important. The present study aims at determining and comparing the prevalence of different genotypes from different parts of India (North, South, East and West). A total of 153 samples representing different regions have been genotyped in our lab. Our studies document a high prevalence of genotype 3 (> 76%) and very low prevalence of genotype 2 (< 2%), as a whole. However, genotype 3a has been found to be the highest (50%) with a decreased frequency of approximately 25% in the case of 3b, approximately 14% in 1b and approximately 10% in 1a, whereas a minimal number (approximately 4%) of genotype 4 has been found only in Southern and Western India.}, } @article {pmid12779085, year = {2003}, author = {Tammen, H and Kreipe, H and Hess, R and Kellmann, M and Lehmann, U and Pich, A and Lamping, N and Schulz-Knappe, P and Zucht, HD and Lilischkis, R}, title = {Expression profiling of breast cancer cells by differential peptide display.}, journal = {Breast cancer research and treatment}, volume = {79}, number = {1}, pages = {83-93}, doi = {10.1023/a:1023309621042}, pmid = {12779085}, issn = {0167-6806}, mesh = {Biomarkers, Tumor/metabolism ; Breast/cytology ; Breast Neoplasms/genetics/*metabolism ; Cells, Cultured ; Epithelial Cells/*metabolism ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Humans ; Proteomics/*methods ; Tumor Cells, Cultured ; }, abstract = {Expression profiling of RNAs or proteins has become a promising means to investigate the heterogeneity of histopathologically defined classes of cancer. Peptides, representing degradation as well as processing products of proteins offer an even closer insight into cell physiology. Peptides are related to the turnover of cellular proteins and are capable to reflect disease-related changes in homoeostasis of the human body. Furthermore, peptides derived from tumor cells are potentially useful markers in the early detection of cancer. In this study, we introduced a method called differential peptide display (DPD) for separating, detecting, and identifying native peptides derived from whole cell extracts. This method is a highly standardized procedure, combining the power of reversed-phase chromatography with mass spectrometry. This technology is suitable to analyze cell lines, various tissue types and human body fluids. Peptide-based profiling of normal human mammary epithelial cells (HMEC) and the breast cancer cell line MCF-7 revealed complex peptide patterns comprising of up to 2300 peptides. Most of these peptides were common to both cell lines whereas about 8% differed in their abundance. Several of the differentially expressed peptides were identified as fragments of known proteins such as intermediate filament proteins, thymosins or Cathepsin D. Comparing cell lines with native tumors, overlapping peptide patterns were found between HMEC and a phylloides tumor (CP) on the one hand and MCF-7 cells and tissue from a invasive ductal carcinoma (DC) on the other hand.}, } @article {pmid12779027, year = {2003}, author = {Kayani, N and Khan, MN and Bhurgri, Y and Gill, S and Nasir, MI and Siddiqui, T}, title = {Male breast cancer.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {53}, number = {3}, pages = {114-116}, pmid = {12779027}, issn = {0030-9982}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*pathology ; Carcinoma, Ductal, Breast/pathology ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {OBJECTIVE: To review cases of male breast cancer.

SETTINGS: Histopathology Section, Department of Pathology, The Aga Khan University, Karachi.

METHOD: Fifty one cases of male breast cancer specimens, received during a period of 10 years, routinely processed and stained with Haematoxylin and Eosin were analyzed. Special stains and Immunohistochemistry were used in difficult cases.

RESULTS: Male breast cancer affected individuals in the sixth and seventh decades of life with a mean age of 56.2 years. Infiltrating ductal carcinoma (IDC) was the predominant type. Skin involvement was seen in 27.45% of the cases. Breast lump was the most common presenting symptom followed by skin ulceration. At the time of presentation 43.13% patients had a tumour size of more than 3 cm.

CONCLUSION: Male breast cancer is a rare disease. Most of our findings correspond to the published local and international data.}, } @article {pmid12778484, year = {2003}, author = {Della Chiesa, M and Vitale, M and Carlomagno, S and Ferlazzo, G and Moretta, L and Moretta, A}, title = {The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors.}, journal = {European journal of immunology}, volume = {33}, number = {6}, pages = {1657-1666}, doi = {10.1002/eji.200323986}, pmid = {12778484}, issn = {0014-2980}, mesh = {Antigens, CD/*analysis ; Cells, Cultured/immunology ; Cytotoxicity, Immunologic ; Dendritic Cells/*immunology ; HLA Antigens/immunology ; HLA-B Antigens/analysis ; HLA-C Antigens/analysis ; Histocompatibility Antigens Class I/immunology ; Humans ; Killer Cells, Natural/classification/*immunology ; Lectins, C-Type/*analysis ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D ; Receptors, Immunologic/*analysis ; Receptors, KIR ; Receptors, KIR3DL1 ; Receptors, Natural Killer Cell ; }, abstract = {The cognate NK-DC interaction in inflamed tissues results in NK cell activation and acquisition of cytotoxicity against immature DC (iDC). This may represent a mechanism of DC selection required for the control of downstream adaptive immune responses. Here we show that killing of monocyte-derived iDC is confined to the NK cell subset that expresses CD94/NKG2A, but not killer Ig-like receptors (KIR). Consistent with these data, the expression of HLA-E (i.e. the cellular ligand of CD94/NKG2A) was down-regulated in iDC. On the other hand, HLA-B and HLA-C down-regulation in iDC was not sufficient to induce cytotoxicity in NK cells expressing KIR3DL1 or KIR2DL. Remarkably, CD94/NKG2A(+)KIR(-) NK cells were heterogeneous in their ability to kill iDC and an inverse correlation existed between their CD94/NKG2A surface density and the magnitude of their cytolytic activity. It is conceivable that the reduced CD94/NKG2A surface density enables these cells to efficiently sense the decrease of HLA-E surface expression in iDC. Finally, most NK cells that lysed iDC did not kill mature DC that express higher amounts of HLA class I molecules (including HLA-E)as compared with iDC. However, a small NK cell subset was capable of killing not only iDC but also mature DC.}, } @article {pmid12774668, year = {2003}, author = {Karamian, NA and Kazanets, EG and Aĭvazova, DKh and Kovrigina, ES and Krasil'nikova, MV and Tokarev, IuN and Smetanina, NS}, title = {[Soluble transferrin receptors: significance and diagnostic value in anemia].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {4}, pages = {40-42}, pmid = {12774668}, issn = {0869-2084}, mesh = {Anemia/blood/*diagnosis/etiology ; Anemia, Iron-Deficiency/blood/*diagnosis ; Child ; Child, Preschool ; Diagnosis, Differential ; Ferritins/blood ; Humans ; Iron/blood ; Receptors, Transferrin/*blood ; beta-Thalassemia/blood/diagnosis ; }, abstract = {The study was undertaken for the purpose of demonstrating a diagnostic importance of determining the level of soluble transferrin receptors not only in the diagnosis of iron-deficiency conditions (IDC) or in the differential diagnosis of anemia in a chronic disease (ACD) and of iron-deficiency anemia (IDA) but also in making a diagnosis in case of transfusion-dependent patients with Cooley's anemia. The iron metabolism (including determination of the serum iron (SI), of the total iron-binding ability (TIBA), of saturation of transferrin with iron (STFI), of serum transferrin (ST), and of soluble transferrin receptors (s-STR) was examined in 31 patients with different-genesis anemias, aged 3 to 7. Diagnoses were made for all children on the basis of the standard clinical-and-laboratory examinations and tests. A pattern of iron-metabolism parameters, typical of this pathology, was detected in all IDC patients; it is noteworthy, that the s-STR concentration amounted in this category to 9.4 +/- 1.35 mg/l, which essentially topped the normal values. It can be concluded on the basis of the obtained results that s-STR can be regarded as a key IDC marker. There was an increased SF (up to 324 +/- 64.5 mkg/L) alongside with hypoferremia in the ACD patients; the s-STR content was found to be within the reference values (3.21 +/- 0.55 mg/L), the determination of s-STR can be regarded as a test in the differential diagnosis of IDC and ACD. The results of s-STR research ranged, in patients with Cooley's anemia, drastically from 0.8 mg/L to 17 mg/L; it is noteworthy, that there was a reliable dependence on an adequacy of the conducted therapy in case of such patients. The highest sSTR values were found in children with the hereditary spherocytic hemolytic anemia (11.85 +/- 2.5 mg/L), which is, apparently, explained by a proliferative super-activity of the bone marrow observed in this pathology.}, } @article {pmid12768632, year = {2003}, author = {Nijhawan, R and Rajwanshi, A and Gautam, U and Gupta, SK}, title = {Cytoplasmic vacuolation, intracytoplasmic lumina, and DPAS staining in ductal carcinoma of the breast.}, journal = {Diagnostic cytopathology}, volume = {28}, number = {6}, pages = {291-294}, doi = {10.1002/dc.10272}, pmid = {12768632}, issn = {8755-1039}, mesh = {Amylases/metabolism ; Biopsy, Needle ; Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Female ; Humans ; *Periodic Acid-Schiff Reaction ; Retrospective Studies ; Vacuoles/chemistry/*pathology ; }, abstract = {A retrospective study was carried out on 30 cases of histologically proven invasive ductal carcinoma of the breast with a prior fine-needle aspiration (FNA) cytology. On evaluating the May-Grünwald-Giemsa (MGG) FNA smears, cytoplasmic vacuolation was observed in 70% cases. Positivity with periodic acid Schiff-positive, diastase-resistant (DPAS) staining was observed in 90% of cases. The chi(2) value on a McNemar test was 4.16. Thus, DPAS staining was significantly superior to MGG staining for picking up cytoplasmic vacuoles (P < 0.05). In 56.67% cases, DPAS staining showed an improvement in score as compared to MGG smears. This was highly significant (P < 0.001) on Wilcoxon matched-pairs signed-ranks test. Applying the strict criteria of thick-walled cytoplasmic vacuoles with a central darkly stained dot, none of our cases revealed true intracytoplasmic lumina. Larger studies are required to establish a role for DPAS staining in separating borderline, in situ, and invasive breast lesions, and to see if such positvity can be incorporated into the grading systems for breast carcinoma.}, } @article {pmid12764685, year = {2003}, author = {Buch, RS and Schmidt, M and Reichert, TE}, title = {[Acute tongue necrosis provoked by epirubicin-cyclophosphamide treatment for invasive ductal breast cancer].}, journal = {Mund-, Kiefer- und Gesichtschirurgie : MKG}, volume = {7}, number = {3}, pages = {175-179}, pmid = {12764685}, issn = {1432-9417}, mesh = {Acute Disease ; Airway Obstruction/chemically induced/pathology ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use ; Breast Neoplasms/*drug therapy ; Carcinoma, Ductal, Breast/*drug therapy ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage/*adverse effects ; Epirubicin/administration & dosage/*adverse effects ; Female ; Humans ; Middle Aged ; Necrosis ; Tongue/drug effects/*pathology ; Tongue Diseases/*chemically induced/pathology ; }, abstract = {CASE: Unilateral necrosis of the tongue is an uncommon symptom of different rare diseases. Previously, it had only been described as an infrequent complication of temporal arteritis or as a side effect of therapy with ergotamine. We present a case of unilateral necrosis of the tongue in a 62-year-old woman with invasive ductal carcinoma of the breast treated with epirubicin and cyclophosphamide.

RESULTS: The necrosis led to a rapid swelling of the tongue and consequently to an airway obstruction necessitating a tracheotomy. After excision of the necrosis, the swelling of the tongue and the airway obstruction subsided.

DISCUSSION: Because of the temporal connection between the occurrence of the necrosis and the administration of chemotherapy, an adverse effect of the administered drugs seems most likely. However, a paraneoplastic pathogenesis cannot be completely excluded. The occurrence of unilateral necrosis of the tongue is a rare complication of the above-mentioned conditions. However, it is important to be aware of the different causes leading to this rare disease in order to initiate the right therapy.}, } @article {pmid12763681, year = {2003}, author = {Moretta, L and Ferlazzo, G and Mingari, MC and Melioli, G and Moretta, A}, title = {Human natural killer cell function and their interactions with dendritic cells.}, journal = {Vaccine}, volume = {21 Suppl 2}, number = {}, pages = {S38-42}, doi = {10.1016/s0264-410x(03)00197-x}, pmid = {12763681}, issn = {0264-410X}, mesh = {Bacterial Infections/immunology ; *Cell Communication ; Dendritic Cells/*physiology ; Histocompatibility Antigens Class I/physiology ; Humans ; Immunity, Innate ; Killer Cells, Natural/*physiology ; }, abstract = {Natural killer (NK) cells have long been considered as "primitive" and "non-specific" effector cells. However, the past 10 years have witnessed dramatic progress in our understanding of how NK cells function and their role in innate defenses. Thanks to specialized inhibitory receptors specific for MHC-class I molecules, they can sense the decrease or loss of these molecules, a typical condition of potentially dangerous cells such as tumor or virally-infected cells. NK cell triggering and lysis of these cells is mediated by several activating receptors and co-receptors that have recently been identified and cloned. While normal cells are usually resistant to the NK-mediated attack, a remarkable exception is represented by dendritic cells (DC). In their immature form (iDC), they are susceptible to NK-mediated lysis because of the expression of low levels of surface MHC-class I molecules. Since the process of DC maturation (mDC) is characterized by the surface expression of high levels of MHC-class I molecules, mDC become resistant to NK cells. Exposure to live bacteria induces rapid DC maturation and, thus, resistance to NK cells. The cross-talk between DC and NK cells is more complex and involves also a DC-dependent NK cell activation and proliferation. Thus, two important players of the innate immunity may be involved in a coordinated regulation of critical events occurring at the interface between innate and adaptive immunity.}, } @article {pmid12759415, year = {2003}, author = {Hoves, S and Krause, SW and Halbritter, D and Zhang, HG and Mountz, JD and Schölmerich, J and Fleck, M}, title = {Mature but not immature Fas ligand (CD95L)-transduced human monocyte-derived dendritic cells are protected from Fas-mediated apoptosis and can be used as killer APC.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {11}, pages = {5406-5413}, doi = {10.4049/jimmunol.170.11.5406}, pmid = {12759415}, issn = {0022-1767}, mesh = {Adenoviridae/genetics ; Antigen-Presenting Cells/*immunology/metabolism ; Apoptosis/genetics/*immunology ; Cell Differentiation/genetics/immunology ; Cell Line ; Cells, Cultured ; Coculture Techniques ; Cytotoxicity Tests, Immunologic ; Dendritic Cells/*immunology/metabolism ; Fas Ligand Protein ; Genetic Vectors ; Green Fluorescent Proteins ; Humans ; Integrases/genetics ; Jurkat Cells ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; Luminescent Proteins/genetics ; Lymphocyte Activation/genetics ; Lymphocyte Depletion ; Membrane Glycoproteins/biosynthesis/*genetics/physiology ; Monocytes/*immunology/metabolism ; Recombination, Genetic ; Solubility ; T-Lymphocyte Subsets/immunology/metabolism/pathology ; Transduction, Genetic ; Viral Proteins/genetics ; fas Receptor/biosynthesis/*physiology ; }, abstract = {Several in vitro and animal studies have been performed to modulate the interaction of APCs and T cells by Fas (CD95/Apo-1) signaling to delete activated T cells in an Ag-specific manner. However, due to the difficulties in vector generation and low transduction frequencies, similar studies with primary human APC are still lacking. To evaluate whether Fas ligand (FasL/CD95L) expressing killer APC could be generated from primary human APC, monocyte-derived dendritic cells (DC) were transduced using the inducible Cre/Loxp adenovirus vector system. Combined transduction of DC by AdLoxpFasL and AxCANCre, but not single transduction with these vectors, resulted in dose- and time-dependent expression of FasL in >70% of mature DC (mDC), whereas <20% of immature DC (iDC) expressed FasL. In addition, transduction by AdLoxpFasL and AxCANCre induced apoptosis in >80% of iDC, whereas FasL-expressing mDC were protected from FasL/Fas (CD95/Apo-1)-mediated apoptosis despite coexpression of Fas. FasL-expressing mDC eliminated Fas(+) Jurkat T cells as well as activated primary T cells by apoptosis, whereas nonactivated primary T cells were not deleted. Induction of apoptosis in Fas(+) target cells required expression of FasL in DC and cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. Induction of apoptosis in Fas(+) target cells required expression of FasL in DC, cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. The present results demonstrate that FasL-expressing killer APC can be generated from human monocyte-derived mDC using adenoviral gene transfer. Our results support the strategy to use killer APCs as immunomodulatory cells for the treatment of autoimmune disease and allograft rejection.}, } @article {pmid12752628, year = {2003}, author = {Chhieng, DC and Tabbara, SO and Marley, EF and Talley, LI and Frost, AR}, title = {Microvessel density and vascular endothelial growth factor expression in infiltrating lobular mammary carcinoma.}, journal = {The breast journal}, volume = {9}, number = {3}, pages = {200-207}, doi = {10.1046/j.1524-4741.2003.09311.x}, pmid = {12752628}, issn = {1075-122X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Carcinoma, Lobular/blood supply/*metabolism/pathology ; Endothelial Growth Factors/*metabolism ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*metabolism ; Lymphokines/*metabolism ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/pathology ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Angiogenesis is an important prognostic factor in infiltrating ductal carcinoma (IDC). Vascular endothelial growth factor (VEGF) stimulates angiogenesis in vivo. VEGF expression has been correlated with high vascularity in IDC. However, little is known about the prognostic significance of microvessel density (MVD) and its correlation with the expression of VEGF in infiltrating lobular carcinoma (ILC). We analyzed tumor samples from 51 patients with primary classic ILC to determine the relationship between tumoral MVD and VEGF expression. Cases of pleomorphic lobular carcinoma and tubulolobular carcinoma were excluded. Five-micron thick sections obtained from formalin-fixed, paraffin-embedded tissue blocks were immunostained with antibodies to factor VIII-related antigen (Dako, Carpenteria, CA) and VEGF (Calbiochem, Boston, MA). The former was used for MVD analysis. The vessel counts from the three most vascular fields (x200 magnification) were recorded and the highest of the vessel counts of the three fields was designated as the MVD. The intensity of VEGF staining and the proportion of cells staining were scored. Both the vessel counts and the scoring of VEGF staining were evaluated by two independent pathologists. The Student's t-test and Wilcoxon rank sum test were used to compare mean MVD and VEGF scores according to various clinical and pathologic features. All significance tests were two-sided with an alpha-level of 0.05. There was good correlation between the MVD of each observer (correlation coefficient 0.775, p < 0.001). There was no correlation of MVD or VEGF score with the size or stage of the tumor. In addition, the MVD or VEGF score was not significantly different between axillary lymph node-positive cases and node-negative cases, between patients with recurrence and those without, and between patients who survived and those who died of disease. There was, however, a weak negative correlation between the MVD and VEGF expression (Spearman correlation coefficient -0.08). Neither MVD or VEGF immunoscore were associated with tumor recurrence or vital status in patients with ILC. The absence of a statistically significant positive correlation between MVD and VEGF expression suggests that other factors may play a more important role in the angiogenesis of ILC.}, } @article {pmid12745101, year = {2003}, author = {Parthenakis, FI and Patrianakos, A and Prassopoulos, V and Papadimitriou, E and Nikitovic, D and Karkavitsas, NS and Vardas, PE}, title = {Relation of cardiac sympathetic innervation to proinflammatory cytokine levels in patients with heart failure secondary to idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {91}, number = {10}, pages = {1190-1194}, doi = {10.1016/s0002-9149(03)00265-0}, pmid = {12745101}, issn = {0002-9149}, mesh = {3-Iodobenzylguanidine/pharmacokinetics ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart/*innervation ; Heart Failure/*blood/*physiopathology ; Humans ; Interleukin-1/blood ; Interleukin-6/blood ; Male ; Middle Aged ; Oxygen Consumption/physiology ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Tumor Necrosis Factor/blood ; Regression Analysis ; Sympathetic Nervous System/*physiology ; Tumor Necrosis Factor-alpha/analysis ; Ventricular Function, Left/physiology ; }, abstract = {Experimental studies have shown that cytokine production by the heart may be regulated by sympathetic nervous system stimulation of cardiac beta-adrenergic receptors. Proinflammatory cytokine levels are increased in heart failure, whereas cardiac fixation of 123-I-metaiodobenzylguanidine (MIBG) has been used to study myocardial adrenergic innervation. This study was designed to assess the relation between cardiac MIBG uptake and circulating levels of proinflammatory cytokines in patients with idiopathic dilated cardiomyopathy (IDC). Forty-seven patients (12 women; mean age 56.5 +/- 9 years) with angiographically proved IDC, in New York Heart Association functional classes II to III, and who had left ventricular ejection fraction 30.6 +/- 9.5%, and 20 healthy controls were studied with planar MIBG. The early (10 minutes) and late (4 hours) heart to mediastinum uptake ratio and washout were calculated. Circulating plasma levels of interleukins (IL)-1 and IL-6, tumor necrosis factor-alpha, and solube receptors of TNF (sTNFR) I and II were measured. The patient group had significantly lower values of MIBG uptake at 10 minutes (p <0.001) and 4 hours (p <0.001) and higher washout (p <0.001) than the controls. Late MIBG uptake was significantly correlated with New York Heart Association class (r = -0.42, p = 0.02), left ventricular ejection fraction (r = 0.34, p = 0.01), left ventricular systolic wall stress (r = -0.40, p = 0.05), oxygen consumption at peak exercise (r = 0.32, p = 0.03), IL-1 (r = -0.55, p <0.001), TNF (r = -0.33, p = 0.02), and sTNFRII (r = -0.44, p = 0.001). Multivariate linear regression analysis revealed that MIBG at 4 hours was independently associated with IL-1 levels (p <0.001). Thus, reduced cardiac sympathetic innervation in heart failure is associated with elevated levels of inflammatory cytokines, suggesting that it has a potential inflammatory effect via modulation of the cardiac production of these cytokines.}, } @article {pmid12738875, year = {2003}, author = {Gill, HK and Ioffe, OB and Berg, WA}, title = {When is a diagnosis of sclerosing adenosis acceptable at core biopsy?.}, journal = {Radiology}, volume = {228}, number = {1}, pages = {50-57}, doi = {10.1148/radiol.2281020447}, pmid = {12738875}, issn = {0033-8419}, mesh = {Adult ; Aged ; *Biopsy ; Breast Neoplasms/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Female ; Fibrocystic Breast Disease/*pathology ; Humans ; Hyperplasia ; Middle Aged ; Prospective Studies ; Sclerosis/pathology ; }, abstract = {PURPOSE: To determine concordance of imaging findings and diagnosis of sclerosing adenosis at histopathologic core biopsy and to establish the accuracy of core biopsy when cancer was coexistent.

MATERIALS AND METHODS: From a database of 1,166 percutaneous biopsies in which sclerosing adenosis was reported, 88 (7.5%) lesions were identified, and imaging and histopathologic findings were reviewed for concordance. Sclerosing adenosis proved to be a minor component at core biopsy for 44 lesions, including one invasive ductal carcinoma, one ductal carcinoma in situ (DCIS), one focus of atypical ductal hyperplasia (ADH), and one atypical lobular hyperplasia. Sclerosing adenosis was a major (> or =50%) component for 44 lesions, including four malignancies, all DCIS manifested as clustered calcifications (pleomorphic [n = 2] or amorphous [n = 2]), and seven foci of ADH manifested as amorphous calcifications. In 30 patients with 33 lesions without atypia or malignancy, sclerosing adenosis was the major finding at core biopsy (21 lesions at 14-gauge core biopsy and 12 at 11-gauge vacuum-assisted biopsy); these patients formed the study population. Mammographic (33 lesions) and sonographic (18 lesions) features were recorded. Twenty-seven lesions had at least 20-month follow-up (n = 25) or excision (n = 2).

RESULTS: One spiculated mass was considered discordant and was excised, showing a prospectively unrecognized radial sclerosing lesion with several 2-5-mm foci of invasive tubular and lobular carcinoma. Seventeen (53%) of 32 lesions manifested as masses; 10 (59%) were circumscribed, five (29%) were indistinctly marginated (one with punctate calcifications), and two (12%) were partially circumscribed and partially obscured (one with amorphous calcifications). Fifteen (47%) lesions manifested as clustered calcifications; nine (60%) were amorphous and indistinct, four (27%) were pleomorphic, and two (13%) were punctate. Of 27 lesions with acceptable follow-up, 26 (96%) were believed to have been accurately sampled at core biopsy. Of six radial sclerosing lesions associated with the original 88 lesions, only three (50%) were prospectively recognized.

CONCLUSION: Sclerosing adenosis is an acceptable result at core biopsy of circumscribed masses and nonpalpable indistinctly marginated masses and for clustered amorphous, pleomorphic, and punctate calcifications. Recognition and reporting of coexistent radial sclerosing lesions is encouraged and may prompt excision. Malignancy can be seen with sclerosing adenosis; core biopsy was accurate in six (86%) of seven coexistent malignancies in this series.}, } @article {pmid12736568, year = {2003}, author = {Tsutsui, S and Ohno, S and Murakami, S and Kataoka, A and Kinoshita, J and Hachitanda, Y}, title = {Histological classification of invasive ductal carcinoma and the biological parameters in breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {2}, pages = {149-152}, doi = {10.1007/BF02967640}, pmid = {12736568}, issn = {1340-6868}, mesh = {Aneuploidy ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; ErbB Receptors/biosynthesis ; Female ; Humans ; Ploidies ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Tumor Suppressor Protein p53/biosynthesis ; }, abstract = {BACKGROUND: The histological classification of invasive ductal carcinoma proposed by the Japanese Breast Cancer Society is based on the appearance of breast cancer invasion. However, few studies have been done to clarify the relationship between the histological classification and other parameters that represent the biological characteristics of individual breast cancer cells.

MATERIALS AND METHODS: We analyzed 1,025 invasive ductal carcinomas, consisting of 424 papillotubular, 330 solid-tubular and 271 scirrhous cases, with regard to the status of estrogen receptor (ER), progesterone receptor (PgR), DNA ploidy, epidermal growth factor receptor (EGFR) and p53 protein.

RESULTS: Absence of ER and PgR, aneuploidy, EGFR positivity and p53 protein positivity were all observed significantly more frequently in solid-tubular tumors than in the other two types. In addition, the number of abnormal features with regard to these 5 biological parameters was also significantly higher in solid-tubular tumors than in the other two types.

CONCLUSION: Abnormalities in the biological parameters listed above were frequently found in the solid-tubular type of invasive ductal carcinoma.}, } @article {pmid12732742, year = {2003}, author = {Snyder, RJ and Stillman, RM and Weiss, SD}, title = {Epidermoid cancers that masquerade as venous ulcer disease.}, journal = {Ostomy/wound management}, volume = {49}, number = {4}, pages = {63-4, 65-6}, pmid = {12732742}, issn = {0889-5899}, mesh = {Biopsy ; Cohort Studies ; *Diagnosis, Differential ; Female ; Florida ; Humans ; Male ; Neoplasms, Squamous Cell/*diagnosis/etiology ; Prevalence ; Skin Neoplasms/*diagnosis/etiology ; Ulcer/complications/*diagnosis/prevention & control ; Ultraviolet Rays/adverse effects ; Vascular Diseases/complications/*diagnosis ; Wound Healing/physiology ; Wounds and Injuries/complications/diagnosis ; }, abstract = {Many lesions originally diagnosed as venous ulcers exhibit characteristics that are strikingly similar to skin cancers and might represent sites of primary carcinomas. To ascertain the frequency of malignancy in patients previously diagnosed with venous ulcer disease, a retrospective cohort review of patients evaluated at a Wound Healing Center in Florida was conducted. Charts of all patients with IDC-9 codes for varicose veins with stasis ulcer, varicose veins with ulcer and inflammation, and venous peripheral insufficiency were reviewed. Only charts of patients with one of these diagnoses and documented clinical varicosities, hemosiderosis, brawny edema, and lesions located at the medial or lateral lower leg were included. Sixty (60) patients were identified. Of these, 20 had lesions that were clinically suspicious for epidermoid skin cancers (ie, showing raised borders and chronic scaling). Biopsies confirmed malignancy in 15 of the 60 ulcers (25%). Of these, eight were squamous cell cancers. Given the high rate of malignancies in this cohort of patients, it is postulated that primary epidermoid cancers may mimic venous ulcers in appearance, location, and symptoms; that Marjolin's ulcers are rare despite their propensity to develop in many different types of wounds; and that patients with a history of venous ulcers and prolonged exposure to ultraviolet rays may benefit from lesion biopsies to test for epidermoid cancers.}, } @article {pmid12715337, year = {2003}, author = {Ramalingam, P and Middleton, LP and Tamboli, P and Troncoso, P and Silva, EG and Ayala, AG}, title = {Invasive micropapillary carcinoma of the breast metastatic to the urinary bladder and endometrium: diagnostic pitfalls and review of the literature of tumors with micropapillary features.}, journal = {Annals of diagnostic pathology}, volume = {7}, number = {2}, pages = {112-119}, doi = {10.1053/adpa.2003.50015}, pmid = {12715337}, issn = {1092-9134}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Papillary/metabolism/pathology/*secondary ; Carcinoma, Transitional Cell/pathology ; Diagnosis, Differential ; Endometrial Neoplasms/metabolism/*secondary ; Female ; Humans ; Immunohistochemistry ; Keratin-7 ; Keratins/metabolism ; Lung Neoplasms/metabolism ; Middle Aged ; Receptors, Estrogen/metabolism ; Urinary Bladder Neoplasms/metabolism/*secondary ; }, abstract = {Carcinomas with micropapillary features have been described in the breast, urinary bladder, lung, and ovary. They are characterized by the presence of micropapillary tufts in clear spaces. Unequivocal vascular invasion is usually present at the periphery of the tumor. Consequently, these tumors have a high propensity for lymph node metastases and high-stage disease. The metastatic carcinoma can consist exclusively of the micropapillary component, which may elicit an erroneous diagnosis if located in the bladder or lung, as in the patient presented herein. We present a case of a 59-year-old woman with a history of bilateral breast carcinoma status post-bilateral mastectomy, chemotherapy, and tamoxifen therapy. She presented with urinary frequency, and a pelvic mass was noted. A biopsy of the endometrium revealed a poorly differentiated carcinoma. Urinary bladder biopsies showed a carcinoma with micropapillary features diagnosed as micropapillary transitional cell carcinoma. She presented to M.D. Anderson Cancer Center (Houston, TX) for further treatment recommendations. The urinary bladder and endometrial biopsies both contained carcinomas with micropapillary features. The mastectomy specimen showed an invasive ductal carcinoma with a significant micropapillary component. The tumor cells from the breast, endometrium, and urinary bladder were positive for cytokeratin (CK) 7 and estrogen receptor and negative for CK20. In view of the morphologic and immunohistochemical profile, the carcinoma in the endometrium and urinary bladder were interpreted as metastatic lesions from the breast primary. Carcinomas with a micropapillary component are morphologically identical in the breast, urinary bladder, and lung. However, micropapillary serous carcinoma has a different appearance more akin to borderline tumors of the ovary. Immunohistochemical stains are useful in distinguishing these lesions in that thyroid transcription factor-1 positivity suggests a lung primary, CK7 and estrogen receptor suggest a breast primary, and both CK7 and CK20 positivity suggest a urinary bladder primary. It is important to exclude metastatic carcinomas with micropapillary features before making a definite diagnosis of a primary tumor. Carcinomas with micropapillary features have a propensity for lymph node metastases and advanced stage disease. This article discusses the differential diagnosis of carcinomas with micropapillary features in different organs.}, } @article {pmid12712492, year = {2003}, author = {Gupta, A and Deshpande, CG and Badve, S}, title = {Role of E-cadherins in development of lymphatic tumor emboli.}, journal = {Cancer}, volume = {97}, number = {9}, pages = {2341-2347}, doi = {10.1002/cncr.11332}, pmid = {12712492}, issn = {0008-543X}, support = {1P 50 CA89018-01/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma in Situ/metabolism/parasitology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/parasitology ; Carcinoma, Lobular/metabolism/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/*metabolism/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: E-cadherin (E-cad) is a cell adhesion molecule that is expressed in normal breast tissue. While loss of E-cad expression is a characteristic feature of lobular carcinoma, it also is observed in infiltrating ductal carcinoma (IDC). The presence of peritumoral intralymphatic emboli also is a poor prognostic feature in IDC. Invasive lobular carcinoma rarely is associated with intralymphatic emboli. In the current study, the authors assessed E-cad expression in cases of IDC with and without intralymphatic tumor emboli to examine the potential role played by these molecules in the development of lymphatic emboli.

METHODS: Fifty patients with high-grade invasive ductal carcinoma--25 with prominent lymphatic invasion (LVI) and intralymphatic tumor emboli and 25 without LVI--were tested for expression of E-cad. For both groups, the intensity and frequency of E-cad expression was evaluated in tumor cells and lymphatic emboli; normal lobules were used as internal controls.

RESULTS: Membranous expression of E-cad was observed in normal lobules and tumor cells in all patients, with the tumor cells exhibiting varying degrees of loss of expression. In the 25 LVI-positive patients, the majority of tumor cells (including intralymphatic emboli) expressed E-cad with an intensity and distribution similar to what was seen in normal lobules. In the LVI-negative patients, the intensity and the distribution of E-cad staining varied significantly. Tumor cells at the tumor-stroma interface showed a greater frequency and intensity of E-cad expression than did cells in the central region of the tumor.

CONCLUSIONS: Strong expression of E-cad was observed in LVI-positive patients with high-grade IDC but not in LVI-negative patients. Emboli also exhibited high-intensity expression. These findings, taken in conjunction with the knowledge that intralymphatic tumor emboli in lobular carcinoma (which is E-cad-negative) are rare, suggest that E-cad plays an important role in tumor development and growth within the lymphatics.}, } @article {pmid12711296, year = {2003}, author = {Mersin, H and Yildirim, E and Gülben, K and Berberoğlu, U}, title = {Is invasive lobular carcinoma different from invasive ductal carcinoma?.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {29}, number = {4}, pages = {390-395}, doi = {10.1053/ejso.2002.1423}, pmid = {12711296}, issn = {0748-7983}, mesh = {Adult ; Aged ; Analysis of Variance ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Lobular/*diagnosis/pathology ; Disease-Free Survival ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Receptors, Estrogen/analysis ; Retrospective Studies ; Survival Analysis ; }, abstract = {AIMS: The purpose of this study is to determine whether the histopathologic features and outcome in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are different, and whether the histologic type is a prognostic factor for outcome.

METHODS: A retrospective cohort study was conducted in consecutive 510 stage I/II breast carcinoma patients who underwent modified radical mastectomy. The features of 65 patients with ILC were compared with those of 445 patients with IDC. In patients with median follow-up period of 44 months, univariate and multivariate prognostic factor analyses for cancer-specific death and relapse were carried out.

RESULTS: The median ages in patients with ILC and those with IDC were 52 and 41 (P=0.04). Tumor size, estrogen receptor positive expression and nodal positivity were not significantly different between the histologic types. Patients with ILC had more frequently (81.5%) low grade tumors and less lymphatic vascular invasion (9.3%) in primary tumor than those with IDC (P<0.05). Whereas the rates of 5-year overall survival were 94% in ILC and 90% in IDC, the rates of 5-year event-free survival were 71 and 67%, respectively (P=NS). Multivariate analyses in all patients demonstrated that tumor size, pathologic lymph node status and age at diagnosis were the most important prognostic factors for overall and event-free survival. Histologic type was not statistically significant for both outcomes.

CONCLUSIONS: Although patients with ILC had older age, low grade tumor and less lymphatic vascular invasion, they had no survival advantage comparing with their counterparts. Histologic type was not an independent prognostic factor for outcome.}, } @article {pmid12711290, year = {2003}, author = {Cocquyt, VF and Blondeel, PN and Depypere, HT and Praet, MM and Schelfhout, VR and Silva, OE and Hurley, J and Serreyn, RF and Daems, KK and Van Belle, SJ}, title = {Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {29}, number = {4}, pages = {361-367}, doi = {10.1053/ejso.2002.1404}, pmid = {12711290}, issn = {0748-7983}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/pathology/surgery ; Carcinoma, Lobular/chemistry/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Cisplatin/administration & dosage ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Mastectomy, Segmental ; Methotrexate/administration & dosage ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {AIM: Preoperative chemotherapy (PCT) is used in primary breast cancer, to facilitate breast conservative surgery (BCS). Clinical and pathologic responses are important prognostic parameters. Biologic markers are needed to individualize treatment.

PATIENTS AND METHODS: One hundred and thirty-five patients with breast carcinoma were treated with PCT, followed by surgery and adjuvant therapy. Clinical response and pathological complete response (pCR), biological markers and type of surgery were compared between invasive ductal (IDC) and invasive lobular carcinoma (ILC).

RESULTS: Overall response (OR) for IDC was 75% compared to 50% for ILC (P=0.0151). Pathological CR was 15% for IDC and 0% for ILC (P=0.0066). Fifty-six percent of the responding patients had BCS, in contrast with 16% of the non-responders. BCS was performed in 50% of patients with IDC, in 38% of the patients with ILC. Salvage surgery was more necessary in ILC (19%) compared to IDC (4%) (P=0.0068). Patients with ILC were more frequently ER-positive and HER-2 negative than patients with IDC.

CONCLUSIONS: Clinical and pathological responses are lower in ILC compared to IDC. After PCT, patients with large ILC should preferably be offered mastectomy with immediate breast reconstruction. However, PCT still remains valuable to evaluate tumor response and biologic factors in vivo.}, } @article {pmid12708494, year = {2003}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Significance of nodal metastatic tumor characteristics in nodal metastasis and prognosis of patients with invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {94}, number = {2}, pages = {181-187}, doi = {10.1111/j.1349-7006.2003.tb01416.x}, pmid = {12708494}, issn = {1347-9032}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Cell Nucleus/ultrastructure ; Combined Modality Therapy ; Disease Progression ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Japan ; Life Tables ; *Lymphatic Metastasis ; Menopause ; Middle Aged ; Mitotic Index ; Neoplasm Invasiveness ; Neoplastic Cells, Circulating ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Treatment Outcome ; }, abstract = {There is no study evaluating the significance of nodal metastatic tumor characteristics in tumor progression of invasive ductal carcinomas (IDCs) of the breast. The purpose of this study was to investigate whether nodal metastatic tumor characteristics play an important role in the tumor progression of IDCs. The subjects of this study were 205 IDC patients with nodal metastases. Significant associations with increased numbers of nodal metastases, and patient outcomes were evaluated by multivariate analyses, in comparison with well-known histological parameters. The numbers of lymph nodes with extra-nodal invasion and with extranodal blood vessel tumor emboli, the distance of extra-nodal blood vessel tumor emboli from the nodes, and the nodal tumor dimensions significantly increased the number of nodal metastases in the multivariate analysis (P<0.001). Cox multivariate analyses showed that the parameters which significantly increased hazard rates (HRs) of disease-free survival (DFS), distant organ metastasis (DOM) and overall survival were 6 or more mitotic figures of nodal metastatic tumors (P<0.05). Six or more lymph nodes with extra-nodal invasion, and an extra-nodal blood vessel tumor emboli dimension of >0.6 mm significantly increased the HRs of DFS and DOM in multivariate analyses (P<0.05). The present study demonstrated the important roles of nodal metastatic tumors in the tumor progression of IDCs.}, } @article {pmid12708491, year = {2003}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Histological characteristics of tumors in blood vessels play an important role in tumor progression of invasive ductal carcinoma of the breast.}, journal = {Cancer science}, volume = {94}, number = {2}, pages = {158-165}, doi = {10.1111/j.1349-7006.2003.tb01413.x}, pmid = {12708491}, issn = {1347-9032}, mesh = {Adult ; Aged ; Apoptosis ; Blood Vessels/*pathology ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Menopause ; Middle Aged ; Mitotic Index ; Multivariate Analysis ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplastic Cells, Circulating/*pathology ; Proportional Hazards Models ; Survival Analysis ; }, abstract = {Whether the characteristics of tumor cells in blood vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast is not known. The purpose of this study was to investigate the significance of the characteristics of tumor cells in blood vessels in relation to tumor progression in 247 IDC patients with blood vessel invasion, in comparison with well-known histological parameters. Blood vessel tumor embolus dimensions were measured. Nuclear atypia, numbers of mitotic and apoptotic figures, and fibrosis grade of tumor cells in blood vessels were assessed. Cox proportional hazard multivariate analyses showed that >2 mitotic figures in blood vessel tumors significantly increased the hazard rates (HRs) of disease-free survival (P=0.002) and initial distant organ metastasis-free survival (IDOMS) in node-negative IDCs (P=0.005), and the HRs of disease-free survival (DFS, P=0.007) and IDOMS (P=0.015) in node-positive IDCs. Apoptotic figures >2 in blood vessel tumor emboli significantly increased the HR of overall survival (P=0.007) in node-positive IDCs. The present study showed the number of mitotic and apoptotic figures in tumor cells in the blood vessels to play a very important role in the tumor progression of IDCs.}, } @article {pmid12707816, year = {2003}, author = {Yahara, T and Koga, T and Yoshida, S and Nakagawa, S and Deguchi, H and Shirouzu, K}, title = {Relationship between microvessel density and thermographic hot areas in breast cancer.}, journal = {Surgery today}, volume = {33}, number = {4}, pages = {243-248}, doi = {10.1007/s005950300055}, pmid = {12707816}, issn = {0941-1291}, mesh = {Breast Neoplasms/*blood supply/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*blood supply/*diagnosis/surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; *Thermography ; }, abstract = {PURPOSE: This study was conducted to evaluate the validity of thermography in breast examination.

METHODS: We performed contact thermography and measured the direct temperature by inserting a needle-type thermometer into the tissue. The core temperature of the tumor (dTt) and the temperature of the tissue surrounding the tumor (dTs) were compared with normal tissue. The microvessel density (MVD) and the MIB-1 labeling index (MIB-1 LI) of the tumor were examined immunohistochemically. The subjects were 48 women with primary invasive ductal carcinoma. The area of the tumor was diagnosed pathologically, and the hot area was measured using thermography.

RESULTS: The dTt was significantly higher than the dTs. Both the dTt and dTs were significantly higher when the thermographical hot area was positive, or when more than four lymph node metastases were found. The dTs was correlated with MVD. A correlation between MVD and tumor temperature measured directly was also confirmed. A higher dTs was related to the dissociated wide area of the thermogram.

CONCLUSION: These findings suggested a relationship between dTs and the high-risk group of breast cancer. We also found that abnormalities in temperature were reflected in thermography and that a higher dTs was related to the dissociated wide area of the thermogram.}, } @article {pmid12706194, year = {2003}, author = {Hall, TJ and Zhu, Y and Spalding, CS}, title = {In vivo real-time freehand palpation imaging.}, journal = {Ultrasound in medicine & biology}, volume = {29}, number = {3}, pages = {427-435}, doi = {10.1016/s0301-5629(02)00733-0}, pmid = {12706194}, issn = {0301-5629}, mesh = {Algorithms ; Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/diagnostic imaging ; Diagnosis, Differential ; Elasticity ; Female ; Fibroadenoma/diagnostic imaging ; Fibrocystic Breast Disease/diagnostic imaging ; Humans ; Image Processing, Computer-Assisted/methods ; Palpation/*methods ; Reproducibility of Results ; Ultrasonography, Mammary/*methods ; }, abstract = {Previous experience with laboratory fixtures and off-line processing of elasticity data showed that problems occurring in data acquisition often resulted in poor elasticity image quality. A system for real-time estimation and display of tissue elastic properties using a clinical ultrasonic imaging system has been developed. A brief description of that system and the initial clinical tests of that system are reported. Experience with real-time freehand elasticity imaging shows that images with high contrast-to-noise ratios are consistently obtained. Images of breast lesions were acquired with freehand palpation using standard linear-array ultrasound (US) transducers. Results in volunteer patients show that high-quality elasticity images are easily obtained from in vivo breast studies. The key element to successful scanning is real-time visual feedback of B-mode and strain images that guide the patient positioning and compression direction. Results show that individual images of axial strain in tissues can be quite misleading, and that a "movie loop" of side-by-side B-mode and strain images provides significantly more information. Our preliminary data suggest that the strain image sequences for various breast pathologies are unique. For example, strain images of fibroadenomas lose contrast with increasing precompression, but those of invasive ductal carcinoma have high negative contrast (dark relative to "normal" tissue) for a wide range of precompression. In addition, a comparison of the lesion area measured in B-mode vs. strain images, for a representative image from the sequence, appears to be a sensitive criterion for separating invasive ductal carcinoma from cyst and fibroadenoma.}, } @article {pmid12692841, year = {2003}, author = {Roylance, R and Droufakou, S and Gorman, P and Gillett, C and Hart, IR and Hanby, A and Tomlinson, I}, title = {The role of E-cadherin in low-grade ductal breast tumourigenesis.}, journal = {The Journal of pathology}, volume = {200}, number = {1}, pages = {53-58}, doi = {10.1002/path.1326}, pmid = {12692841}, issn = {0022-3417}, mesh = {Alleles ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; Genes, Neoplasm/genetics ; Humans ; Immunohistochemistry/methods ; Mutation/genetics ; Neoplasm Invasiveness ; }, abstract = {Grade I invasive ductal breast carcinomas have a specific pattern of genetic aberrations, namely gain of 1q and loss of 16q. This pattern is very similar to the changes seen in invasive lobular breast carcinomas (ILCs). The gene on 16q involved in ILC is known to be E-cadherin (CDH1). This study has investigated whether the same gene is responsible for grade I invasive ductal carcinoma (IDC), using allele imbalance analysis, mutation screening, and immunohistochemistry (IHC). The data suggest that despite the shared pattern of genetic aberrations seen in grade I IDC and ILC, CDH1 is not the target gene in low-grade ductal tumourigenesis.}, } @article {pmid12687856, year = {2003}, author = {Grimm, W and Herzum, I and Müller, HH and Christ, M}, title = {Value of heart rate variability to predict ventricular arrhythmias in recipients of prophylactic defibrillators with idiopathic dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {26}, number = {1P2}, pages = {411-415}, doi = {10.1046/j.1460-9592.2003.00060.x}, pmid = {12687856}, issn = {0147-8389}, mesh = {Cardiomyopathy, Dilated/complications/mortality/*physiopathology/surgery ; *Defibrillators, Implantable ; Electrocardiography, Ambulatory ; Female ; *Heart Rate ; Heart Transplantation ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Risk Factors ; Stroke Volume ; Survival Analysis ; Survival Rate ; Tachycardia, Ventricular/diagnosis/etiology/*prevention & control ; Ventricular Fibrillation/diagnosis/etiology/*prevention & control ; }, abstract = {This study investigated the relation between heart rate variability (HRV) measured as standard deviation of normal to normal RR intervals (SDNN) on baseline 24-hour ambulatory electrocardiogram (ECG) and subsequent appropriate implantable cardioverter defibrillator (ICD) interventions in 70 patients with idiopathic dilated cardiomyopathy (IDC) in whom ICDs were implanted prophylactically in the presence of a low left ventricular ejection fraction (LVEF). During 43 +/- 26 months of follow-up, 26 of 70 (37%) study patients with IDC received one or more appropriate ICD interventions for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) documented by electrograms stored in the ICD. Mean SDNN at ICD implant was 94 +/- 33 ms. No difference was found between patients with (90 +/- 25 ms) versus without (96 +/- 37 ms) appropriate ICD interventions for VT or VF during follow-up. Multivariate Cox regression analysis of baseline clinical characteristics including age, gender, LVEF, NYHA functional class, nonsustained VT on Holter, history of syncope, left bundle branch block, baseline medication and HRV revealed LVEF as the only significant predictor of arrhythmia. These findings do not support the use of HRV measured as SDNN on 24-hour ambulatory ECG to select patients with IDC for prophylactic ICD therapy.}, } @article {pmid12687844, year = {2003}, author = {Fauchier, L and Marie, O and Casset-Senon, D and Babuty, D and Cosnay, P and Fauchier, JP}, title = {Ventricular dyssynchrony and risk markers of ventricular arrhythmias in nonischemic dilated cardiomyopathy: a study with phase analysis of angioscintigraphy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {26}, number = {1P2}, pages = {352-356}, doi = {10.1046/j.1460-9592.2003.00048.x}, pmid = {12687844}, issn = {0147-8389}, mesh = {Cardiomyopathy, Dilated/*complications/*diagnostic imaging/physiopathology ; Death, Sudden, Cardiac/etiology ; Disease Progression ; Electrocardiography ; *Gated Blood-Pool Imaging ; Humans ; Middle Aged ; Prognosis ; Risk Factors ; Tachycardia, Ventricular/diagnosis/*etiology ; Ventricular Dysfunction/diagnosis/etiology ; Ventricular Fibrillation/diagnosis/*etiology ; }, abstract = {Biventricular pacing is a new form of treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. Limited information is available regarding the relationship between ventricular dyssynchrony and risk markers of ventricular arrhythmias in idiopathic dilated cardiomyopathy (IDC). In 103 patients with IDC, Fourier phase analysis of both ventricles was performed from equilibrium radionuclide angiography (ERNA). The difference between the mean phase of the LV and RV was a measure of interventricular dyssynchrony, and the standard deviations of the mean phases in each ventricle measured intraventricular dyssynchrony. There were no significant differences in inter- and intraventricular dyssynchrony between patients with versus without histories of sustained VT or VF, nonsustained VT, abnormal signal-averaged ECG, or induced sustained monomorphic VT. Dyssynchrony was not related to decreased heart rate variability (HRV). LV and interventricular dyssynchrony were weakly related to QT duration and QT dispersion. During a follow-up of 27 +/- 23 months, 21 patients had major adverse cardiac events (MACE), including 7 cardiac deaths, 11 progression of heart failure leading to cardiac transplantation, and 3 sustained VT/VF. The only independent predictors of MACE were an increased standard deviation of LV mean phase (P = 0.003), a decreased HRV (standard deviation of normal-to-normal intervals, P = 0.004), and histories of previous VT/VF (P = 0.03) or nonsustained VT (P = 0.04). In conclusion, left intraventricular dyssynchrony evaluated with ERNA was an independent predictor of MACE in IDC and was not related to usual risk markers of ventricular arrhythmias. This may have implications for resynchronization therapy and/or the use of implantable cardioverter defibrillators in IDC.}, } @article {pmid12679975, year = {2002}, author = {Belicza, M and Lenicek, T and Glasnović, M and Elez, M and Gladić, V and Marton, I and Zuteković, S and Jurlina, H and Kusić, Z and Cvrtila, D and Strnad, M and Tomas, D and Cupić, H and Kruslin, B}, title = {[Change in the occurrence of breast cancer in hospital registries (1980-2000)].}, journal = {Lijecnicki vjesnik}, volume = {124}, number = {11-12}, pages = {347-353}, pmid = {12679975}, issn = {0024-3477}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology ; Breast Neoplasms, Male/epidemiology ; Croatia/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Radioactive Hazard Release ; Registries ; Ukraine ; Warfare ; }, abstract = {The aim of our retrospective study was to analyze distribution of histological types, age of patients and hormonal dependency of breast cancer cases in the period 1980-2000 using computer database "Thanatos". This period was divided with regard to the war into a pre-war (1980-1990), war (1991-1995) and post-war period (1996-2000). We also paid attention to the Chernobyl accident (pre-Chernobyl from 1980-1986 and post-Chernobyl from 1987-2000). Special attention was focused on the period during the war mainly due to the fact that very little data exist in literature dealing with the war as a stress factor that may have induced and promoted carcinogenesis. During this twenty-one year period 2296 patients were diagnosed with breast cancer. In the female population of 2274, 2228 (98%) of these were ductal and only 46 (2%) were invasive lobular carcinomas. In all of the male cases (22) the cancer was pathohistologically verified as the invasive ductal type. The male:female ratio was 1:103. Comparing the pre-war and war periods we found a more than double increase in the male:female ratio (from 1:131 to 1:66). We observed similar results when we looked at the period after the Chernobyl incident where the ratio increased from 1:139 to 1:79. When we analyzed the distribution of histological types we found a significant increase in lobular carcinomas during the post-war period, from 1.1% to 5.5%; this increase was less significant for the post-Chernobyl period (1.0% to 3.3%). The average age of the patients with invasive ductal carcinomas increased from 56.7 yrs during the pre-war period to 59.7 yrs during the war and finally to 61.1 yrs during the post-war period. The average age of males with breast cancer decreased from 63.6 and 63.5 during the pre-war and war periods to 58.8 yrs during the post-war period. These results suggest that the war could have influenced the shift in the age of occurrence of breast cancer in both sexes appearing in younger males and in females in their postmenopausal period. The most commonly diagnosed stage of invasive ductal carcinoma during the war and post-war periods was T1N0MX, but in the controlled pre-war period the most frequently diagnosed stage was T2N1MX. With this we see that the increase in the age of the patient is not due to a more advanced pTNM stage which suggests that the increased age of our patients seeking medical help is not due to the incapacitating effects that the war may have on people needing medical attention. Our results showed that most of the patients were ER positive (72% throughout the twenty-one year period) and their average rate and number increase with the age of the patient. We found a significant drop in hormone dependent tumors in the period from 1991-95, which could mean that tumors in a war environment manifest a more aggressive phenotype. Our results show that the war within our region most likely had an effect on some clinical parameters involving breast cancer patients. Possible effects caused by "Chernobyl" could not be proved due to the overwhelming effect that war had upon the patients within this region.}, } @article {pmid12685185, year = {2003}, author = {Rajesh, L and Dey, P and Joshi, K}, title = {Fine needle aspiration cytology of lobular breast carcinoma. Comparison with other breast lesions.}, journal = {Acta cytologica}, volume = {47}, number = {2}, pages = {177-182}, doi = {10.1159/000326500}, pmid = {12685185}, issn = {0001-5547}, mesh = {Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Neoplasm Invasiveness/*pathology ; Observer Variation ; Prospective Studies ; Reproducibility of Results ; Retrospective Studies ; }, abstract = {OBJECTIVE: To analyze the detailed cytomorphology of lobular breast carcinoma and to compare the cytologic smears of benign, borderline and infiltrating duct carcinoma.

STUDY DESIGN: Fine needle aspiration cytology (FNAC) smears of histopathologically proven infiltrating lobular carcinoma (ILC), infiltrating ductal carcinoma (IDC), borderline lesions and benign breast lesions were selected for study. Detailed cytomorphologic analysis of the smears was carried out on hematoxylin and eosin- and May-Grünwald-Giemsa--stained slides, and a comparison of results was done. The various cytologic features were also graded semi-quantitatively with the numerical score; logistic regression analysis was done.

RESULTS: There were 25 cases of ILC, 30 of IDC, and 10 borderline and 18 benign lesions. Cytologic diagnosis of malignancy on FNAC smears of ILC was offered in 19 cases; of them, 2 cases were diagnosed as ILC. The remaining six cases were diagnosed as borderline (four) and benign lesions (two). Overall sensitivity in detection of malignancy in ILC cases was 76%. FNAC smears of ILC showed moderate (52%) to abundant (32%) cellularity. The cells of ILC were arranged both in clusters and in dissociation (72%). Individual cells were monomorphic (40%) to mildly pleomorphic (60%), and the cells were smaller. The cells showed a smooth, regular nuclear margin; bland chromatin; and indistinct nucleoli. Indian file arrangement was frequently observed (28%). Nuclear molding (28%) and intranuclear inclusions (16%) were also noted. Intracytoplasmic lumina were seen in occasional cases. Logistic regression analysis was carried out, and a comparison between lobular carcinoma and ductal carcinoma, and borderline and benign lesions was done. Logistic regression analysis of cytomorphologic features showed that cellularity and nuclear margin irregularities were the two most important features to distinguish ILC from IDC. In comparison to borderline lesions, cell dissociation was more common in ILC. The salient cytologic features that helped to distinguish ILC from benign lesions was cell size, cellularity, cell uniformity and chromatin pattern.

CONCLUSION: There are overlapping cytologic features between ILC, IDC and borderline breast lesions on FNAC smears. Logistic regression analysis may be helpful in this regard.}, } @article {pmid12679736, year = {2003}, author = {Nio, Y and Omori, H and Toga, T and Hashimoto, K and Itakura, M and Koike, M and Yano, S and Higami, T}, title = {Immunohistochemical expression of receptor-tyrosine kinase c-kit protein in invasive ductal carcinoma of the pancreas.}, journal = {Anti-cancer drugs}, volume = {14}, number = {4}, pages = {313-319}, doi = {10.1097/00001813-200304000-00009}, pmid = {12679736}, issn = {0959-4973}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Benzamides ; Carcinoma, Pancreatic Ductal/drug therapy/*metabolism/pathology ; Female ; Humans ; Imatinib Mesylate ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/*metabolism/mortality/pathology ; Piperazines/therapeutic use ; Proto-Oncogene Proteins c-kit/*biosynthesis ; Pyrimidines/therapeutic use ; Retrospective Studies ; Survival Rate ; }, abstract = {The expression of receptor tyrosine kinase c-kit and its biologic significance in pancreatic cancer are unclear. We studied the expression of c-kit protein (c-KIT) in resectable invasive ductal carcinomas (IDCs) of the pancreas, in order to assess whether a selective c-kit inhibitor, STI571 (Glivec), may be applied for the treatment of pancreatic IDCs. This study included 72 pancreatic IDC patients who received a pancreatectomy between 1982 and 2002. The expression of c-KIT was analyzed retrospectively by immunohistochemistry. c-KIT was expressed in 78% (56/72) of the pancreatic IDCs. c-KIT expression did not correlate with any clinicopathological factor of pancreatic IDC and c-KIT expression had no significant influence on the survival of the patients. The survival rate of the adjuvant chemotherapy (ACT) (+) group was significantly higher than that of the ACT (-) group, but c-KIT expression had no significant effects on the efficacy of the ACT. Multivariate analysis indicated that the pTNM stage, grade and ACT were all significant variables for survival in IDCs overall. As c-KIT was expressed in 78% of the pancreatic IDCs, it suggests that STI571 may be a beneficial agent for chemotherapy against human pancreatic IDCs.}, } @article {pmid12677894, year = {2002}, author = {Skálová, A and Stárek, I and Vanĕcek, T and Kucerová, V and Plank, L and Szépe, P}, title = {[Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization].}, journal = {Ceskoslovenska patologie}, volume = {38 Suppl 1}, number = {}, pages = {27-34}, pmid = {12677894}, issn = {1210-7875}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma/*chemistry/genetics ; Female ; *Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Parotid Neoplasms/*chemistry/genetics ; Receptor, ErbB-2/*analysis ; Retrospective Studies ; *Salivary Ducts ; }, abstract = {Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.}, } @article {pmid12677891, year = {2002}, author = {Mrhalová, M and Kodet, R}, title = {[Indications for treatment in invasive ductal carcinoma of the breast with Herceptin from the aspect of laboratory diagnosis--study of the ERBB-2 protein and determination of the number of copies of the ERBB2 gene. Review].}, journal = {Ceskoslovenska patologie}, volume = {38 Suppl 1}, number = {}, pages = {4-14}, pmid = {12677891}, issn = {1210-7875}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/*therapeutic use ; Breast Neoplasms/chemistry/*drug therapy/genetics ; Carcinoma, Ductal, Breast/chemistry/*drug therapy/genetics ; Female ; Gene Amplification ; Genes, erbB-2/*genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*analysis ; Trastuzumab ; }, abstract = {Overexpression of the ERBB-2 protein has become a target of the anti-neoplastic treatment in patients with invasive duct carcinomas of the breast with a monoclonal antibody trastuzumab (Herceptin, Genentech). From this reason the immunohistochemical (IHC) evaluation of ERBB-2 protein expression is crucial. However, there are patients in whom the IHC investigation is biased by a subjective evaluation among cases considered negative (in the range of 1+) and positive (2+), and among cases considered positive 2+ and 3+. In such cases it is advisable to complement the IHC investigation by detection of copy numbers of the ERBB2 gene with fluorescence in situ hybridization (FISH). The overexpression of the protein is caused by the gene amplification in a majority of cases. The patients, whose carcinomas show overexpression of the ERBB-2 protein and the overexpression is caused by a significant gene amplification, profit from the Herceptin therapy. In this review we focus also on the methodology of FISH in paraffin sections and tissue imprints with respect to the detection of copy numbers of chromosome 17 and the ERBB2 gene.}, } @article {pmid12673207, year = {2003}, author = {Kominsky, SL and Argani, P and Korz, D and Evron, E and Raman, V and Garrett, E and Rein, A and Sauter, G and Kallioniemi, OP and Sukumar, S}, title = {Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast.}, journal = {Oncogene}, volume = {22}, number = {13}, pages = {2021-2033}, doi = {10.1038/sj.onc.1206199}, pmid = {12673207}, issn = {0950-9232}, support = {P50 CA88843/CA/NCI NIH HHS/United States ; }, mesh = {Breast/cytology/*metabolism ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/pathology ; Carcinoma, Lobular/*chemistry/pathology ; Cell Adhesion/drug effects ; Cells, Cultured/chemistry/drug effects ; Claudins ; DNA Methylation ; Epithelial Cells/chemistry ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Hepatocyte Growth Factor/pharmacology ; Humans ; Membrane Proteins/biosynthesis/*deficiency/genetics/physiology ; Neoplasm Invasiveness/*genetics ; Neoplasm Proteins/biosynthesis/*deficiency/genetics/physiology ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Sequence Analysis, DNA ; Severity of Illness Index ; Tight Junctions/*chemistry ; Tumor Cells, Cultured/chemistry/drug effects ; }, abstract = {Claudins are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, as determined by both RT-PCR (9/10) and Western analysis (6/8). Immunohistochemical (IHC) analysis of ductal carcinoma in situ (DCIS) and IDC showed that the loss of CLDN-7 expression correlated with histological grade in both DCIS (P<0.001, n=38) and IDC (P=0.014, n=31), occurring predominantly in high-grade (Nuclear and Elston grade 3) lesions. Tissue array analysis of 355 IDC cases further confirmed the inverse correlation between CLDN-7 expression and histological grade (P=0.03). This pattern of expression is consistent with the biological function of CLDN-7, as greater discohesion is typically observed in high-grade lesions. In line with this observation, by IHC analysis, CLDN-7 expression was lost in the vast majority (13/17) of cases of lobular carcinoma in situ, which is defined by cellular discohesion. In fact, inducing disassociation of MCF-7 and T47D cells in culture by treating with HGF/scatter factor resulted in a loss of CLDN-7 expression within 24 h. Silencing of CLDN-7 expression correlated with promoter hypermethylation as determined by methylation-specific PCR (MSP) and nucleotide sequencing in breast cancer cell lines (3/3), but not in IDCs (0/5). In summary, these studies provide insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate.}, } @article {pmid12661895, year = {2003}, author = {Tang, P and Hajdu, SI and Conte, CC and Filardi, DA}, title = {Incidental finding of mammary carcinoma in lumpectomy specimens.}, journal = {Annals of clinical and laboratory science}, volume = {33}, number = {1}, pages = {23-31}, pmid = {12661895}, issn = {0091-7370}, mesh = {Adipose Tissue/pathology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Carcinoma, Lobular/*pathology/surgery ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Stromal Cells/pathology ; }, abstract = {More and more breast lumpectomies are being performed due to mammographic screening, and both in situ and invasive breast carcinomas are being detected earlier and smaller in size. The objective of this study was to determine the presence of incidental microscopic breast carcinoma in mammography-guided lumpectomy specimens. A prospective study was carried out by processing in surgical pathology approximately 9,000 breast lumpectomy specimens during a 2.5-yr period so that the entire specimens were embedded for microscopic examination. Excluded from the study were cases with grossly or microscopically identified carcinomas greater than 10 mm2, and non-invasive carcinomas diagnosed in association with invasive carcinoma. Cases with multifocal carcinomas, prior diagnosis of breast cancer, or prior history of breast biopsy were also excluded. Carcinomas present in the same tissue blocks as the clinically suspected lesions such as palpable nodules, microcalcification, or other mammographic abnormalities were excluded as well. Fifty cases of incidental microscopic mammary carcinoma were found including 8 infiltrating ductal carcinomas (IDC), 2 infiltrating lobular carcinomas (ILC), 21 intraductal carcinomas (DCIS), and 19 lobular carcinomas in situ (LCIS). All of the lesions were solitary, located in indistinct loosely arranged fibrous and adipose stromal tissues, and the majority of them were near or at the inked excisional margins. Physicians who care for patients with breast cancer should be aware of the existence of these minute breast carcinomas that are often near or at the surgical margins. The significance of these microscopic findings for therapeutic strategy and prognosis should be determined by long-term follow-up.}, } @article {pmid12653946, year = {2003}, author = {Skálová, A and Stárek, I and Vanecek, T and Kucerová, V and Plank, L and Szépe, P and Di Palma, S and Leivo, I}, title = {Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry.}, journal = {Histopathology}, volume = {42}, number = {4}, pages = {348-356}, doi = {10.1046/j.1365-2559.2003.01600.x}, pmid = {12653946}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma/genetics/*metabolism/secondary ; Female ; Gene Amplification ; Gene Expression/*genetics ; *Genes, erbB-2 ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Parotid Neoplasms/genetics/*metabolism/pathology ; *Receptor, ErbB-2/genetics/metabolism ; *Salivary Ducts/pathology ; }, abstract = {AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed.

METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma.

CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.}, } @article {pmid12653184, year = {2002}, author = {Stoupel, E and Petrauskiene, J and Abramson, E and Kalediene, R and Sulkes, J}, title = {Distribution of monthly deaths, solar (SA) and geomagnetic (GMA) activity: their interrelationship in the last decade of the second millennium: the Lithuanian study 1990-1999.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {56 Suppl 2}, number = {}, pages = {301s-308s}, doi = {10.1016/s0753-3322(02)00306-2}, pmid = {12653184}, issn = {0753-3322}, mesh = {Aged ; *Electromagnetic Fields/adverse effects ; Female ; Humans ; Lithuania/epidemiology ; Male ; Mortality/*trends ; Multivariate Analysis ; *Periodicity ; *Solar Activity ; *Statistical Distributions ; }, abstract = {Thirty percent of cardiovascular deaths cannot be explained by known risk factors. In this study, we sought links between 1) circannual rhythmicity, solar activity (SA) - sunspot number, solar radioflux and geomagnetic activity (GMA) - Ap., Cp., Am. with monthly number of deaths looking for environmental influence on mortality at the end of the second millennium. The Lithuanian national death data from for 120 consecutive months according to the IDC (1990 - 1999, n = 424925 deaths) was studied: 157189 from IHD (72144 male, 85045 female), 50228 from stroke (19062 male, 31166 female), 33722 from accidents (26193 male, 7529 female), 10655 from road accidents (8127 male, 2528 female) and 14810 from suicide (12137 male, 2673 female), 217508 - non cardiovascular (134308 male, 83200 female). Monthly death numbers (total, < 65y, 65-74, > 74y old for IHD and Stroke, and by gender) were compared with time of year, SA and GMA indices obtained from the National Geophysical Data and National Space Services Center, USA. Circannual rhythmicity indices, Pearson correlation coefficients and their probabilities were obtained and analyzed. The interrelationships of deaths from IHD and stroke and some other pathologies were also studied. In addition a multivariate linear regression analysis was done in order to evaluate the influence of time (month), Solar (S.A.) and Geomagnetic (GMA) activity on the temporal distribution of deaths. The total IHD monthly death number was significantly linked with GMA indices (r = 0.2-0.24, p = 0.03-0.075), but not with SA. IHD correlated with SA (r = 0.25-0.27, p = 0.006-0.0026), only in the 74 year age group. p = 0.0001) In the 65-74 age group, there was an inverse relationship with SA (r = -0.46-0.44) and no significant relationship to GMA. The IHD death number was correlated with GMA only in the < 65 and > 74 year age group (r = 0.30-0.36, p = 0.001-0.001). 2) Stroke-related deaths showed an inverse correlation with SA and GMA only for the 65-74y age group (r = -0.5, p = 0.0001 - SA, r = -0.4, p = 0.0001- GMA) and with GMA at age < 65 only for males (r = 0.20-0.25, p = 0.03-0.04). 3) Both IHD and stroke were strongly circannual rhythmic with acrophase at month 1.27 (IHD) and 1.32 (stroke) - first half of February, (p = 0.0001). 4) The IHD / stroke death ratio was correlated both with SA and GMA (r = 0.35, p 0.0001 - SA, r = 0.40-0.44, p = 0.0001 - GMA). 5) There was a strong inverse monthly deaths correlation between IHD and suicide (n = 14,810, r = -0.53, p = 0.0001). Stroke and suicide were also related, but to a much weaker extent (r = -0.217, p = 0.017). Accidents were inverse related to S.A. (r = -0.286, p = 0.0015), but not to GMA. Road Accidents - with both S.A. (r = 0.427, p < 0.0001) and GMA (r = 0.258, p = 0.004); with acrophases in October for road and November for other fatal accidents. Non cardiovascular deaths were annually rhythmic only for female - acrophase in early February, and for both gender inverse related to S.A. (r = -0.57, p < 0.0001) but not with GMA. Suicide victims had their acrophase in July (p < 0.0001) and were inverse related to S.A. (r = -0.6, p < 0.0001) and GMA (r = -0.27, p = 0.002). At the onset of the third millennium, the temporal distribution of deaths is still related to environmental physical activity. Those links differ for each of the pathologies, and by age and gender.}, } @article {pmid12651069, year = {2003}, author = {Gansuvd, B and Hagihara, M and Higuchi, A and Ueda, Y and Tazume, K and Tsuchiya, T and Munkhtuvshin, N and Kato, S and Hotta, T}, title = {Umbilical cord blood dendritic cells are a rich source of soluble HLA-DR: synergistic effect of exosomes and dendritic cells on autologous or allogeneic T-Cell proliferation.}, journal = {Human immunology}, volume = {64}, number = {4}, pages = {427-439}, doi = {10.1016/s0198-8859(03)00016-8}, pmid = {12651069}, issn = {0198-8859}, mesh = {Adult ; *Antigen Presentation ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/cytology/*immunology ; Cell Differentiation ; Cells, Cultured ; Dendritic Cells/cytology/*immunology ; Female ; Fetal Blood/cytology/*immunology ; HLA-DR Antigens/*blood/metabolism ; Humans ; Lymphocyte Activation ; Monocytes/immunology ; Pregnancy ; T-Lymphocytes/immunology ; Transport Vesicles/*metabolism ; }, abstract = {In this study, we compared soluble HLA-DR (sHLA-DR) production in the culture supernatants of various cell sources [T and B cells, monocytes and dendritic cells (DCs) either from adult peripheral blood (PB) or umbilical cord blood (UCB)]. DCs produced the highest amount of sHLA-DR molecules as compared to other cell sources, with UCB DCs producing the highest amount. Different kinetics of sHLA-DR production were found between immature and mature UCB DCs (mDC, iDC) (derived either from CD34(+) or CD14(+) cells). Maximum production of sHLA-DR was observed in 72-hour culture supernatants of both CD34- and CD14-derived mDCs, whereas it peaked in the 24-hour culture supernatants from iDC. sHLA-DR molecules were pelleted after sequential centrifugation from UCB CD34(+) DCs and were found to contain both 36 kD alpha-chain and 29 kD beta-chain of HLA-DR, CD86, and Fas molecules. These sHLA-DR containing vesicles/exosomes alone evoked weak proliferative responses from autologous and allogeneic T cells, but the immune response was significantly increased when vesicles/exosomes were presented with DCs.}, } @article {pmid12636465, year = {2003}, author = {Li, CI and Anderson, BO and Daling, JR and Moe, RE}, title = {Trends in incidence rates of invasive lobular and ductal breast carcinoma.}, journal = {JAMA}, volume = {289}, number = {11}, pages = {1421-1424}, doi = {10.1001/jama.289.11.1421}, pmid = {12636465}, issn = {0098-7484}, support = {R01 CA 85913/CA/NCI NIH HHS/United States ; T32 CA 09168/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology ; Carcinoma, Ductal, Breast/*epidemiology ; Carcinoma, Lobular/*epidemiology ; Estrogen Replacement Therapy/statistics & numerical data/*trends ; Female ; Humans ; Incidence ; Middle Aged ; Risk ; SEER Program ; United States/epidemiology ; }, abstract = {CONTEXT: Research has suggested that use of combined estrogen and progestin hormone replacement therapy (CHRT) increases breast cancer risk and that CHRT use is more strongly associated with the risk of invasive lobular breast carcinoma than that of invasive ductal carcinoma. Lobular carcinoma is less common than ductal carcinoma but can be more difficult to diagnose because of its subtle elusive infiltrative pattern.

OBJECTIVE: To evaluate trends in invasive lobular and ductal carcinoma incidence rates from 1987 through 1999, during which time use of CHRT increased in the United States.

DESIGN: Descriptive epidemiologic study.

SETTING: Nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and that cover Atlanta, Ga; Detroit, Mich; San Francisco-Oakland, Calif; Seattle, Wash; and Connecticut, Hawaii, Iowa, New Mexico, and Utah.

POPULATION: Women 30 years of age and older residing in the areas covered by the 9 SEER registries.

MAIN OUTCOME MEASURES: Proportional changes in incidence rates of invasive lobular and ductal carcinoma among women with no prior history of breast cancer.

RESULTS: A total of 190 458 women were included in this analysis who were identified through the registries as having invasive breast cancer; 7682 of the 198 140 potentially eligible women (ie, those identified as not having in situ breast cancer) were excluded from this analysis because stage of cancer was unknown. Invasive breast cancer incidence rates adjusted for age and for SEER historic stage increased 1.04-fold (95% confidence interval [CI], 1.004-1.07) from 1987-1999 (206.7/100 000 to 214.1/100 000, age-adjusted). However, incidence rates of tumors classified as lobular increased 1.52-fold (95% CI, 1.42-1.63), and those classified as mixed ductal-lobular increased 1.96-fold (95% CI, 1.80-2.14); rates of these types combined increased 1.65-fold (95% CI, 1.55-1.78) (19.8/100 000 to 33.4/100 000, age-adjusted). In contrast, ductal carcinoma rates remained largely constant (153.8/100 000 to 155.3/100 000, age-adjusted; proportional change, 1.03 [95% CI, 0.99-1.06]). The proportion of breast cancers with a lobular component increased from 9.5% in 1987 to 15.6% in 1999.

CONCLUSIONS: Ductal carcinoma incidence rates remained essentially constant from 1987-1999 while lobular carcinoma rates increased steadily. This increase presents a clinical challenge given that lobular carcinoma is more difficult to detect than ductal carcinoma by both physical examination and mammography.}, } @article {pmid12629061, year = {2003}, author = {Kitamura, N and Murata, S and Abe, H and Hanasawa, K and Tsukashita, S and Tani, T}, title = {Obstructive jaundice in a metastatic tumor of the pancreas from breast cancer: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {33}, number = {2}, pages = {93-97}, doi = {10.1093/jjco/hyg018}, pmid = {12629061}, issn = {0368-2811}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*complications/*secondary ; Cholestasis/*etiology/pathology/therapy ; Fatal Outcome ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Pancreatic Neoplasms/*complications/*secondary ; }, abstract = {Metastatic pancreas tumors from breast cancer are comparatively uncommon and patients with this tumor usually remain asymptomatic during their life. A 55-year-old woman presented with obstructive jaundice following mastectomy for invasive ductal carcinoma. We diagnosed obstructive jaundice due to a pancreatic tumor demonstrated on computed tomography and performed percutaneous transhepatic cholangio-drainage. Although the patient recovered from the jaundice, she had exacerbation of pneumonia from which she died. At autopsy, invasive ductal carcinoma was found in the pancreas tumor. Immunohistochemical staining was performed to confirm whether the pancreatic tumor was primary or secondary. Human milk fat globules 1 and 2 and gross cystic disease fluid protein-15, which characteristically exist in normal breast tissue or breast carcinoma, were expressed both in the primary breast tumor and the pancreatic tumor. In contrast, both the anti-estrogen receptor and anti-progesterone receptor antibodies stained positively in the primary breast cancer; however, neither of them was positive in the metastatic pancreatic tumor. We report a rare case of a patient who presented with obstructive jaundice from a pancreatic tumor metastasizing from breast cancer and in whom immunohistochemical staining using the antibodies unique to the mammary gland was effective for the diagnosis of this secondary tumor.}, } @article {pmid12627717, year = {2003}, author = {Hirayama, K and Honda, Y and Sako, T and Okamoto, M and Tsunoda, N and Tagami, M and Taniyama, H}, title = {Invasive ductal carcinoma of the mammary gland in a mare.}, journal = {Veterinary pathology}, volume = {40}, number = {1}, pages = {86-91}, doi = {10.1354/vp.40-1-86}, pmid = {12627717}, issn = {0300-9858}, mesh = {Animals ; Carcinoma, Ductal, Breast/pathology/*veterinary ; Fatal Outcome ; Female ; Horse Diseases/*pathology ; Horses ; Immunohistochemistry/veterinary ; Mammary Neoplasms, Animal/*pathology ; }, abstract = {A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.}, } @article {pmid12622431, year = {2002}, author = {Moriya, T and Kimura, W and Sakurai, F and Semba, S and Ozawa, K and Hirai, I and Fuse, A}, title = {Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor.}, journal = {International journal of gastrointestinal cancer}, volume = {31}, number = {1-3}, pages = {191-197}, pmid = {12622431}, issn = {1537-3649}, mesh = {Adenocarcinoma, Mucinous/*pathology/*surgery ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Pancreatic Ductal/*pathology ; Carcinoma, Papillary/*pathology/*surgery ; Fatal Outcome ; Humans ; Immunohistochemistry ; Immunophenotyping ; Male ; *Neoplasm Recurrence, Local ; Neoplasms, Second Primary/*pathology ; Pancreatic Neoplasms/*pathology/*surgery ; }, abstract = {Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.}, } @article {pmid12607598, year = {2002}, author = {Lee, WY}, title = {Frequent loss of BRCA1 nuclear expression in young women with breast cancer: an immunohistochemical study from an area of low incidence but early onset.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {10}, number = {4}, pages = {310-315}, doi = {10.1097/00129039-200212000-00004}, pmid = {12607598}, issn = {1541-2016}, mesh = {Adult ; Age Factors ; Aged ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Nucleus/metabolism ; Female ; Gene Expression ; Genes, BRCA1 ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Young women with breast cancer have a more unfavorable outcome and advanced disease than older women. This study was initiated to determine the difference in tumor biology between younger and older groups. One hundred fifty-five patients with invasive ductal carcinoma, not otherwise specified, comprised the study group, including 50 women aged less than 35 years, 50 aged 36 to 50 years, and 55 aged more than 50 years. Histopathologic parameters, including tumor size, combined histologic grade, and axillary lymph node status, were studied. Biomarkers, including estrogen receptor status, tumor proliferation rate as determined by Ki-67, and gene expressions of c-erbB-2, p53, bcl-2, and BRCA1, were determined by immunohistochemistry. Comparisons of the distribution of these parameters in three age groups were performed. Breast cancer occurring in women aged less than 35 years had a significantly higher incidence of large tumor, high proliferation rate, and loss of nuclear BRCA1 expression (44.0% versus 22.0% or 23.6%) than in the two older age groups. Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2-negative tumor than that found in the 36- to 50-year age group. No difference was found in lymph node status and c-erbB-2 and p53 gene expressions between the age groups. Loss of BRCA1 nuclear expression significantly correlated with higher histologic grade and high Ki-67 index (P < 0.05) in group A. These findings suggested that women aged less than 35 years have frequent loss of nuclear BRCA1 expression, which may be responsible for the specific tumor biology different from older women. However, c-erbB-2 and p53 gene expressions seem to have no important role in the adverse tumor behavior of breast cancer in young women.}, } @article {pmid12607595, year = {2002}, author = {Lee, JS and Kim, HS and Jung, JJ and Kim, YB and Lee, MC and Park, CS}, title = {Expression of vascular endothelial growth factor in invasive ductal carcinoma of the breast and the relation to angiogenesis and p53 and HER-2/neu protein expression.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {10}, number = {4}, pages = {289-295}, doi = {10.1097/00129039-200212000-00001}, pmid = {12607595}, issn = {1541-2016}, mesh = {Adult ; Aged ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/*blood supply/*metabolism/pathology ; Endothelial Growth Factors/*metabolism ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/*metabolism ; Lymphokines/*metabolism ; Middle Aged ; Neovascularization, Pathologic ; Prognosis ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {The vascular endothelial growth factor (VEGF) appears to play an important role in tumor angiogenesis. The p53 and HER-2/neu genes have been thought to regulate VEGF expression. Although the most common genetic alterations described in human breast cancer are p53 gene mutations and HER-2/neu gene amplification, there is a paucity of reports concerning a possible association between VEGF expression and p53 and HER-2/neu expression. Ninety-nine invasive ductal carcinoma cases were examined by immunohistochemical studies with anti-VEGF, anti-p53, anti-HER-2/neu, and anti-CD34 antibodies. Computerized image analysis was used to evaluate the microvessel density (MVD). Eighty-eight tumors (88.9%) were classified as being VEGF positive. Twenty-five tumors (25.3%) showed p53 protein expression, while 36 tumors (35.4%) expressed the HER-2/neu protein. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). The tumors expressing VEGF had a significantly higher MVD than those that did not (P < 0.05). VEGF expression was significantly associated with p53 protein expression (P < 0.01). In double VEGF and p53 immunohistochemical stained sections, the two markers were generally expressed in the same tumor cells. The cancer stage was the only independent prognostic factor of disease-free and overall survival. The authors' results suggest that VEGF expression plays a role in promoting angiogenesis in invasive ductal carcinoma of the breast, and p53 is likely to be involved in regulating VEGF expression.}, } @article {pmid12601182, year = {2003}, author = {Lee, SG and Orel, SG and Woo, IJ and Cruz-Jove, E and Putt, ME and Solin, LJ and Czerniecki, BJ and Schnall, MD}, title = {MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results.}, journal = {Radiology}, volume = {226}, number = {3}, pages = {773-778}, doi = {10.1148/radiol.2263020041}, pmid = {12601182}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Chi-Square Distribution ; Contrast Media ; Feasibility Studies ; Female ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging/*methods ; Middle Aged ; Neoplasms, Multiple Primary/*diagnosis ; Risk Factors ; Statistics, Nonparametric ; }, abstract = {PURPOSE: To investigate the role of screening magnetic resonance (MR) imaging in the detection of synchronous contralateral breast cancer in patients with newly diagnosed breast cancer.

MATERIALS AND METHODS: Between January 1999 and July 2001, 182 patients with newly diagnosed breast cancer (after either core or excisional biopsy with positive or close margins of resection) underwent bilateral contrast material-enhanced MR imaging at 1.5 T with a dedicated bilateral breast multicoil array. The contralateral breast was imaged for cancer screening. Family history of breast cancer, index cancer histology, breast density, and age at diagnosis of first breast cancer were assessed as potential risk factors for synchronous contralateral breast cancer.

RESULTS: Fifteen patients (8.2%) had a suspicious enhancing lesion depicted in the contralateral breast. Seven patients (3.8%) had malignant results: ductal carcinoma in situ (DCIS) in four, invasive ductal carcinoma with DCIS in two, and invasive ductal carcinoma in one. Eight patients (4.4%) had benign results: fibrocystic changes in four, atypical ductal hyperplasia in two, atypical lobular hyperplasia and focal lobular carcinoma in situ in one, and ductal hyperplasia in one. Six patients with negative MR findings underwent prophylactic mastectomy; no malignancy was found. No significant differences were noted among patients with true-positive (n = 7), false-positive (n = 8), or negative (n = 167) MR findings with regard to family history of breast cancer (P <.27), index cancer histology (P <.19), breast density (P <.34), or age at diagnosis of first breast cancer (P <.10).

CONCLUSION: The preliminary results demonstrate the feasibility of using MR imaging of the breast in a screening role, specifically to evaluate the contralateral breast in patients with newly diagnosed breast cancer to detect mammographically and clinically occult synchronous breast cancer.}, } @article {pmid12590171, year = {2002}, author = {Liu, J and Ferrari, M}, title = {Mechanical spectral signatures of malignant disease? A small-sample, comparative study of continuum vs. nano-biomechanical data analyses.}, journal = {Disease markers}, volume = {18}, number = {4}, pages = {175-183}, doi = {10.1155/2002/874157}, pmid = {12590171}, issn = {0278-0240}, mesh = {Breast Neoplasms/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Humans ; Models, Theoretical ; Nanotechnology/*methods ; Neoplasm Invasiveness ; Ultrasonography ; }, abstract = {Thin sections from human breast biopsies were employed to perform a differential analysis of the ultrasound spectral responses from invasive ductal carcinoma and normal tissue. A non-destructive testing methodology was employed, yielding the reflection coefficients as function of frequency in the clinical ultrasound range. The spectral responses were simulated both in the context of continuum and nano-biomechanics, with the objective of quantifying the physical properties that determine the differences in the spectral signature of normal vs. malignant tissue. The properties that were employed for the theoretical reconstruction of the spectra were: the density, the continuum and the nanomechanical elastic constants, and the nanomechanical theory internodal distance. The latter is a measure of the depth-of-penetration of mechanical actions between contiguous tissue elements. Together with vectorial descriptors of the tissue spatial arrangement, the internodal distance variable affords the quantitative incorporation of tissue architectural data in the theoretical model. In this paper, the validity of the nanomechanical approach to tissue characterization is discussed, and its potential extensions to biomolecular marker-based cancer diagnostics and therapeutics are considered.}, } @article {pmid12585661, year = {2002}, author = {Zuiani, C and Francescutti, GE and Londero, V and Zunnui, I and Bazzocchi, M}, title = {Ductal carcinoma in situ: is there a role for MRI?.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {21}, number = {3 Suppl}, pages = {89-95}, pmid = {12585661}, issn = {0392-9078}, mesh = {Aged ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; Image Enhancement ; *Magnetic Resonance Imaging/methods ; Mammography ; Middle Aged ; Neoplasm Invasiveness ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {The purpose of our study is to report personal experience about 28 cases of Ductal Carcinoma In Situ (DCIS) studied with Magnetic Resonance Imaging (MRI). From September 1995 to December 2001, 28 women affected by DCIS lesions underwent contrast enhanced MRI. All patients were submitted previously to mammographic examination. The results of histopathological examination included: 19 DCIS and 9 DCIS with associated microinvasive component or microfoci of invasive ductal carcinoma (IDC). MRI was performed with a 1 T system. A three dimensional fast low-angle shot (FLASH) pulse sequence was used, with a repetition time (TR) of 14 ms, an echo time (TE) of 7 ms and a flip angle of 25 degrees. We evaluated the morphologic features of the enhancement, the enhancement rate and the signal time intensity curve. On MRI 26 out of 28 (92.85%) DCIS lesions showed contrast uptake. 17 out of 19 pure DCIS lesions demonstrated contrast enhancement: 5 showed a low, 7 indeterminate and 5 a strong enhancement. Morphologically, the enhancing lesion was focal in 9, segmental in 5 and linear branching in 3. Wash out was found in 5 cases, plateau curve in 9 and Type I curve in 3. There were 5 cases of multifocality. All DCIS with associated microinvasion demonstrated contrast enhancement: 2 out of 9 cases showed a low enhancement, 4 out of 9 showed an indeterminate enhancement and 3 out of 9 showed a strong enhancement. Morphologically the enhancing lesion was focal in 3 out of 9, segmental in 5 and linear branching in 1. The wash out was demonstrated in 4 cases out of 9, plateau curve in 4 and Type I curve in 1. There were 3 cases of multifocality. In conclusion, MR imaging sensitivity for DCIS detection is lower than that achieved for invasive breast cancer; however, contrast enhanced MR imaging can depict mammographically occult foci of DCIS. The MR imaging technique is of complementary value in better description of tumor size and in additional malignant lesions detection.}, } @article {pmid12582956, year = {2003}, author = {Lerda, R and Cardelli, C}, title = {Breathing and propelling in crawl as a function of skill and swim velocity.}, journal = {International journal of sports medicine}, volume = {24}, number = {1}, pages = {75-80}, doi = {10.1055/s-2003-37195}, pmid = {12582956}, issn = {0172-4622}, mesh = {Apnea ; Arm/physiology ; Humans ; Male ; *Respiration ; Swimming/*physiology ; Task Performance and Analysis ; }, abstract = {This study analyzes apnea (A), exhalation (E), and inhalation (I) duration with respect to stroke organization in front crawl as a function of inhalation side, swim velocity and performance level. Thirty-six male subjects comprised two groups based on performance level: more expert (ME) and less expert (LE) swimmers. All swam with one inhalation per cycle to the preferred side at speeds corresponding to two specific race paces: 100-m (V100) and 800-m (V800) velocities. The breathing arm (BA) is located on the inhalation side, and the non-breathing arm (NBA) on the opposite side. The sound of air passing in and out of the swimmers' mouths was captured by a microphone and synchronized with video frames. Stroke phases and arm coordination were identified by video analyses. Arm coordination was quantified using two indices of coordination (IdC) corresponding to the lag time between the beginning of the BA (IdC-BA) or NBA (IdC-NBA) propulsive action and the end of that of the other arm. As velocity increases, the ME are observed to reduce I during BA recovery (-19.4 +/- 31.6 %, p < 0.05) while the LE increase A (+ 34.8 +/- 25.2 %, p < 0.05) during BA entry, catch and recovery and NBA pull and push. These variations are related to a lengthening of the pull for both arms at the expense of BA non-propulsive phases. At V100, the ME have greater E (p < 0.05) during BA entry and catch (+ 21.1 +/- 38.2 %) and NBA push (+ 26.3 +/- 39.5 %) compared to the LE. This increase, at the expense of A, corresponds to a shorter BA push and NBA recovery. At V800, the ME exhibit a longer A (p < 0.05) during BA recovery (+ 19.9 +/- 33.2 %) and NBA pull (+ 24.2 +/- 31.5 %), and decreased I during NBA push and pull. These differences are related to a shortening of BA recovery and pull and a longer push for both arms. These breath and stroke adaptations correspond to an increase in stroke rate and IdC-BA with the velocity and performance level. This study points out the breathing-propelling aspects of coordination that indicate technical skill in swimming.}, } @article {pmid12570949, year = {2003}, author = {Arenal, A and Glez-Torrecilla, E and Ortiz, M and Villacastín, J and Fdez-Portales, J and Sousa, E and del Castillo, S and Perez de Isla, L and Jimenez, J and Almendral, J}, title = {Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease.}, journal = {Journal of the American College of Cardiology}, volume = {41}, number = {1}, pages = {81-92}, doi = {10.1016/s0735-1097(02)02623-2}, pmid = {12570949}, issn = {0735-1097}, mesh = {Adult ; Aged ; Body Surface Potential Mapping/methods ; Catheter Ablation/*methods ; Electrophysiologic Techniques, Cardiac/methods ; Feasibility Studies ; Female ; Heart Diseases/complications/surgery ; Humans ; Incidence ; Male ; Middle Aged ; Tachycardia, Ventricular/complications/epidemiology/*surgery ; Treatment Outcome ; }, abstract = {OBJECTIVES: We sought to evaluate the feasibility of identifying and ablating the substrate of unmappable ventricular tachycardia (VT).

BACKGROUND: Noninducible and nonstable VT cannot be ablated by the conventional approach.

METHODS: We studied 24 patients with documented monomorphic VT. Twenty-one patients had ischemic cardiomyopathy, two had nonischemic cardiomyopathy, and one had tetralogy of Fallot. Twelve patients had an implantable cardioverter-defibrillator. Conventional activation mapping was not possible in 18 patients: at least 1 of the clinical VTs or the clinical VT was not inducible in 12 patients, and VT was not tolerated in 6 patients. This group had experienced between 1 and 106 VT episodes in the month before the ablation procedure. Endocardial electroanatomic activation maps (Carto System) during sinus rhythm (SR) and right ventricular apex (RVA) pacing were obtained to define areas for which an electrogram displayed isolated, delayed components (E-IDC). These electrograms were characterized by double or multiple components separated by >/=50 ms.

RESULTS: One area of E-IDC was recorded in 20 patients, and 2 or more were recorded in 4 patients. In 23 patients, these areas were detected during RVA pacing; in only 14 during SR. An E-IDC area related to the clinical VT was identified in each patient. Ablation guided by E-IDC suppressed all but one clinical VT whose inducibility suppression was tested. During a follow-up period of 9 +/- 4 months, three patients had recurrences of the ablated VT and two of a different VT.

CONCLUSIONS: Electrograms with IDCs related to clinical VT can be identified in the majority of patients during RVA pacing. Radiofrequency ablation of E-IDC seems effective in controlling unmappable VT.}, } @article {pmid12565210, year = {2003}, author = {Lee, EH and Wylie, EJ and Bourke, AG and Bastiaan De Boer, W}, title = {Invasive ductal carcinoma arising in a breast hamartoma: two case reports and a review of the literature.}, journal = {Clinical radiology}, volume = {58}, number = {1}, pages = {80-83}, doi = {10.1053/crad.2003.1133}, pmid = {12565210}, issn = {0009-9260}, mesh = {Aged ; Breast Diseases/diagnostic imaging/*pathology ; Breast Neoplasms/diagnostic imaging/pathology ; Carcinoma, Ductal, Breast/diagnostic imaging/*pathology ; Female ; Hamartoma/diagnostic imaging/*pathology ; Humans ; Mammography/methods ; Neoplasm Invasiveness ; Precancerous Conditions/diagnostic imaging/*pathology ; Ultrasonography, Mammary/methods ; }, } @article {pmid12560691, year = {2003}, author = {Spiegel, AJ and Butler, CE}, title = {Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction.}, journal = {Plastic and reconstructive surgery}, volume = {111}, number = {2}, pages = {706-711}, doi = {10.1097/01.PRS.0000041440.12442.05}, pmid = {12560691}, issn = {0032-1052}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/etiology/*surgery ; Carcinoma, Ductal, Breast/etiology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/etiology/*surgery ; Follow-Up Studies ; Humans ; *Mammaplasty ; *Mastectomy, Segmental ; *Mastectomy, Subcutaneous ; Middle Aged ; Neoplasm Recurrence, Local/*etiology ; Postoperative Complications/*etiology ; Reoperation ; Retrospective Studies ; Risk ; }, abstract = {Skin-sparing mastectomy with immediate breast reconstruction can provide an excellent cosmetic result. Despite its increasing popularity, few studies have assessed the risk of recurrence when the procedure is used for the treatment of ductal carcinoma in situ. To evaluate the oncologic safety of skin-sparing mastectomy used for the treatment of ductal carcinoma in situ, the recurrence rate was analyzed. Patients with ductal carcinoma in situ or invasive carcinoma or both who underwent skin-sparing mastectomy with immediate breast reconstruction between 1985 and 1994 and had a follow-up period of at least 6 years were included in this retrospective analysis. The recurrence rates were determined for invasive carcinoma (with or without foci of ductal carcinoma in situ) and ductal carcinoma in situ alone. A total of 221 patients were included, 177 patients with invasive carcinoma and 44 patients with ductal carcinoma in situ alone. The immediate breast reconstructions were performed with transverse rectus abdominis muscle (TRAM) flaps in 62 percent of patients, implants in 34 percent of patients, and latissimus dorsi myocutaneous flaps (with or without implants) in 4 percent of patients. The local recurrence rate was zero of 44 for patients with ductal carcinoma in situ and 5.6 percent (10 of 177) for patients with invasive carcinoma during a mean follow-up period of 9.8 years. There was a 6.8 percent (12 of 177) metastatic recurrence rate in the invasive carcinoma group. All recurrences were invasive ductal carcinoma. Of the patients with ductal carcinoma in situ alone, none developed metastatic disease. The combined metastatic and local recurrence rates for the invasive carcinoma group (n = 177) with each type of reconstruction were 13 percent (14 of 110), 12 percent (seven of 60), and 14 percent (one of seven) for TRAM flaps, implants, and latissimus dorsi flaps, respectively. The risk of recurrence following skin-sparing mastectomy and immediate breast reconstruction for ductal carcinoma in situ is low during this follow-up period. Therefore, skin-sparing mastectomy with immediate breast reconstruction seems to be a safe oncologic treatment option for ductal carcinoma in situ; however, a longer follow-up period is important to determine the long-term risk of recurrence.}, } @article {pmid12560343, year = {2003}, author = {Königshoff, M and Wilhelm, J and Bohle, RM and Pingoud, A and Hahn, M}, title = {HER-2/neu gene copy number quantified by real-time PCR: comparison of gene amplification, heterozygosity, and immunohistochemical status in breast cancer tissue.}, journal = {Clinical chemistry}, volume = {49}, number = {2}, pages = {219-229}, doi = {10.1373/49.2.219}, pmid = {12560343}, issn = {0009-9147}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis/*genetics ; Female ; Gene Dosage ; Heterozygote ; Humans ; Immunohistochemistry ; Middle Aged ; Polymerase Chain Reaction ; Receptor, ErbB-2/*genetics ; }, abstract = {BACKGROUND: Amplification of the oncogene HER-2/neu influences breast cancer pathogenesis, and therapy and prognosis may be affected by the degree of amplification. The extent of amplification or protein overexpression typically is analyzed by fluorescence in situ hybridization or immunohistochemistry (IHC), but quantitative PCR techniques have been described that may provide alternatives to these methods.

METHODS: We developed a rapid-cycle, real-time PCR assay for quantification of HER-2/neu gene status. We compared results obtained with this assay with short tandem repeat findings by capillary electrophoresis (CE) and with protein overexpression assessments by IHC. Accuracy and linearity were tested on cell lines and with simulation experiments. We analyzed the amplification of HER-2/neu in 51 clinical tissue samples from patients with suspected breast cancer.

RESULTS: The intra- and interrun CVs for HER-2/neu quantification by real-time PCR were 12% and 18%, and the CV for different simulated amplification and deletion experiments was <7%. The results for HER-2/neu gene status in cell lines matched the values reported in literature. We detected HER-2/neu amplification by real-time PCR in 11 samples, all from patients with invasive ductal carcinoma. Allelic imbalances were found by CE analyses in three samples and by protein overexpression in six samples; five of these were also detected by real-time PCR. Comparison of the quantification results with known prognostic indices yielded results similar to those reported in several other published studies.

CONCLUSIONS: The assay is suitable for accurate and precise quantification of HER-2/neu copy numbers in tumor tissue samples obtained in routine clinical practice.}, } @article {pmid12559622, year = {2003}, author = {Luppi, P and Rudert, W and Licata, A and Riboni, S and Betters, D and Cotrufo, M and Frati, G and Condorelli, G and Trucco, M}, title = {Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection.}, journal = {Human immunology}, volume = {64}, number = {2}, pages = {194-210}, doi = {10.1016/s0198-8859(02)00798-x}, pmid = {12559622}, issn = {0198-8859}, mesh = {Adolescent ; Adult ; Aged ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cardiomyopathy, Dilated/etiology/*immunology/virology ; Child ; Chlorocebus aethiops ; Complementarity Determining Regions/genetics ; Cytokines/biosynthesis/genetics ; DNA, Viral/isolation & purification ; Diabetes Mellitus, Type 1/genetics ; Enterovirus B, Human/*pathogenicity ; Enterovirus Infections/complications/*immunology/virology ; Female ; Gene Expression Profiling ; Gene Frequency ; Gene Rearrangement, T-Lymphocyte ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor beta ; Genetic Predisposition to Disease ; HLA-DQ Antigens/genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; HLA-DR Antigens/genetics ; HLA-DR4 Antigen/genetics ; HLA-DRB1 Chains ; Humans ; Lymphocyte Activation ; Macrophages/immunology ; Male ; Middle Aged ; Myocarditis/etiology/*immunology/virology ; Myocardium/*immunology/metabolism ; RNA, Messenger/analysis ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; T-Lymphocyte Subsets/*immunology ; Vero Cells/virology ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II alleles associated with susceptibility to type 1 diabetes (HLA-DR4 and HLA-DQA1*04/05/06 alleles) were remarkably infrequent in IDC patients (p < 0.005), thus suggesting that they might confer protection against IDC. Finally, mRNA for interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha was detected in the cardiac specimens, although at a lower level compared with specimens from hearts without signs of viral infections. We conclude that CVB infection of the human myocardium is associated with a selective, yet polyclonal activation of different T-cell subsets in genetically susceptible individuals. This immune response may play a critical role in modulating disease progression after viral infections.}, } @article {pmid12558664, year = {2003}, author = {Dmytrasz, K and Tartter, PI and Mizrachy, H and Chinitz, L and Rosenbaum Smith, S and Estabrook, A}, title = {The significance of atypical lobular hyperplasia at percutaneous breast biopsy.}, journal = {The breast journal}, volume = {9}, number = {1}, pages = {10-12}, doi = {10.1046/j.1524-4741.2003.09103.x}, pmid = {12558664}, issn = {1075-122X}, mesh = {Aged ; Biopsy, Needle ; Breast/*pathology ; Breast Diseases/diagnosis/*pathology ; Breast Neoplasms/diagnosis/*pathology ; Calcinosis/diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/pathology ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; Middle Aged ; Precancerous Conditions/diagnosis/*pathology ; Retrospective Studies ; Vacuum ; }, abstract = {Atypical lobular hyperplasia (ALH) is occasionally found in specimens obtained by percutaneous stereotactic vacuum-assisted breast biopsy for microcalcifications. Since malignancy is often found at surgical excision when atypical ductal hyperplasia is found at percutaneous biopsy, we reviewed our pathologic findings from surgery for ALH at percutaneous biopsy. This was a retrospective review of all percutaneous breast biopsy specimens for mammographic microcalcifications obtained from a single institution over a 30-month period. The pathologic findings from percutaneous biopsy were correlated with the radiologic appearance and the pathology from surgical excision. ALH was found in 13 of 766 (1.7%) stereotactic vacuum-assisted core needle biopsies performed for mammographic microcalcifications. Subsequent surgery in six patients revealed ductal carcinoma in situ (DCIS) in two patients and one case of invasive ductal carcinoma. Surgical excision is indicated for areas with ALH discovered by percutaneous biopsy for mammographic microcalcifications.}, } @article {pmid12558663, year = {2003}, author = {Bauer, VP and Ditkoff, BA and Schnabel, F and Brenin, D and El-Tamer, M and Smith, S}, title = {The management of lobular neoplasia identified on percutaneous core breast biopsy.}, journal = {The breast journal}, volume = {9}, number = {1}, pages = {4-9}, doi = {10.1046/j.1524-4741.2003.09102.x}, pmid = {12558663}, issn = {1075-122X}, mesh = {Aged ; Biopsy, Needle ; Breast/*pathology ; Breast Neoplasms/diagnosis/epidemiology/*pathology ; Carcinoma in Situ/diagnosis/epidemiology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/diagnosis/epidemiology/pathology ; Carcinoma, Lobular/diagnosis/epidemiology/*pathology ; Female ; Humans ; Hyperplasia ; Mammography ; Middle Aged ; Papilloma, Intraductal/diagnosis/epidemiology/pathology ; Practice Guidelines as Topic ; Retrospective Studies ; Treatment Outcome ; Ultrasonography, Mammary ; }, abstract = {The management of lobular neoplasia (LN) found on percutaneous core biopsy remains a clinical dilemma. The purpose of this study was to establish guidelines for the management of LN when obtained on percutaneous core needle biopsy. A retrospective review of the Breast Imaging Tissue Sampling Database at New York Presbyterian Hospital-Columbia Comprehensive Breast Center was performed from 1998 to 2000. A total of 1460 percutaneous core breast biopsies were performed using 11- or 14-gauge needles with LN identified in 43 biopsies from 34 patients. Eleven biopsies were ultrasound guided for nonpalpable masses and 32 were stereotactically guided for mammographically detected densities (10) and microcalcifications (22). The 43 LN biopsies were divided into three groups based on additional findings associated with LN on core biopsy: group I (n = 19), LN with invasive cancer or ductal carcinoma in situ (DCIS); group II (n = 11), LN plus a second indication for open surgical biopsy, such as atypical ductal hyperplasia (ADH), radial scar, phyllodes tumor, or intraductal papilloma; and group III (n = 13), LN plus benign fibrocystic changes. In group I, 19 of 19 biopsies (100%) yielded invasive cancer or DCIS on surgical biopsy versus 3 of 11 (27%) for group II, and 1 of 13 (8%) for group III. Outcomes in group III are described as follows: three patients were lost to follow-up, three patients did not undergo surgical biopsy but demonstrated more than 1 year of mammographic stability following core biopsy. Of the remaining seven patients, two had LN and ADH on surgical biopsy (one had a contralateral cancer), one had atypical lobular hyperplasia (with a contralateral cancer), two had LN and benign fibrocystic changes, one had LN and intraductal papilloma, and one had LN and invasive ductal carcinoma (IDC) with DCIS (with a contralateral cancer). These results suggest that surgical biopsy is indicated for patients with LN when found on core biopsy and when the biopsy demonstrates invasive cancer, DCIS, or other indications for surgical biopsy such as ADH, or in the examination of a patient with a synchronous contralateral breast cancer. The diagnosis of LN alone without these indications on percutaneous biopsy may not warrant routine surgical biopsy.}, } @article {pmid12541444, year = {2000}, author = {Zhou, HB and Mukai, Y}, title = {[Synthesis of fluorescent derivatization reagent 2-(4-carboxyphenyl)-naphthoimidazole and its application in the determination of alcohols by high performance liquid chromatography].}, journal = {Se pu = Chinese journal of chromatography}, volume = {18}, number = {1}, pages = {10-13}, pmid = {12541444}, issn = {1000-8713}, mesh = {Alcohols/*analysis ; Cholesterol/*analysis ; Chromatography, High Pressure Liquid/*methods ; Fluorescent Dyes ; Imidazoles/*chemical synthesis ; Indicators and Reagents/*chemistry ; Naphthalenes/*chemical synthesis ; }, abstract = {A new sensitive pre-column fluorescent derivatization method, which employs high performance liquid chromatography(HPLC) with fluorometric detection, for the determination of alcohols is described. The alcohols were transformed into the corresponding fluorescent esters by treating with 2-(4-carboxyphenyl)-naphthoimidazole in dichloromethane in the presence of 4-piperidinopyridine (PIP) and 1-isopropyl-3-(3-dimethylaminopropyl)-1-carbodiimide perchlorate(IDC) at 80 degrees C for 10 min. The resultant mixture was analyzed by HPLC on a reversed phase column(Zorbax Bp C8, 4.6 mm i.d. x 250 mm, 5 microns) with acetonitrile-methanol (volume ratio was 90:10) as mobile phase, and the sample volume was 20 microL. Monitored excitation and emission wavelengths were 345 nm and 485 nm respectively in determination of the alcohol. The calibration curve of cholesterol is linear between 0 and 2.5 g/L with correlation coefficient of 0.9992. The average recovery was 96.15% with RSD of 1.39%. The lowest detectable mass concentration of cholesterol was 1.0 microgram/L (S/N = 3).}, } @article {pmid12538684, year = {2003}, author = {Brown, JA and Dorfman, DM and Ma, FR and Sullivan, EL and Munoz, O and Wood, CR and Greenfield, EA and Freeman, GJ}, title = {Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {170}, number = {3}, pages = {1257-1266}, doi = {10.4049/jimmunol.170.3.1257}, pmid = {12538684}, issn = {0022-1767}, support = {AI39671/AI/NIAID NIH HHS/United States ; AI41584/AI/NIAID NIH HHS/United States ; CA84500/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD ; *Antigens, Surface ; Apoptosis/immunology ; Apoptosis Regulatory Proteins ; *B7-1 Antigen ; B7-H1 Antigen ; Binding, Competitive/immunology ; Blood Proteins/*antagonists & inhibitors/biosynthesis/immunology/*metabolism ; Breast Neoplasms/immunology/metabolism ; CD4-Positive T-Lymphocytes/*immunology/metabolism ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Cytokines/*biosynthesis ; Dendritic Cells/cytology/*immunology ; Female ; Humans ; Immunoglobulin Fab Fragments/metabolism/pharmacology ; Intercellular Signaling Peptides and Proteins ; Ligands ; Lymphocyte Activation/*immunology ; Membrane Glycoproteins ; Mice ; Monocytes/immunology/metabolism ; Organ Specificity/immunology ; Peptides/*antagonists & inhibitors/immunology/*metabolism ; Programmed Cell Death 1 Ligand 2 Protein ; Programmed Cell Death 1 Receptor ; Proteins/antagonists & inhibitors/immunology/metabolism ; Tumor Cells, Cultured ; }, abstract = {Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses.}, } @article {pmid12534733, year = {2003}, author = {Tsang, FH and Lo, JJ and Wong, JL and Lee, FC and Chow, LW}, title = {Application of image-guided biopsy for impalpable breast lesions in Chinese women.}, journal = {ANZ journal of surgery}, volume = {73}, number = {1-2}, pages = {23-25}, doi = {10.1046/j.1445-2197.2003.02614.x}, pmid = {12534733}, issn = {1445-1433}, mesh = {Biopsy/*instrumentation/methods ; Breast Neoplasms/diagnostic imaging/ethnology/*pathology ; Carcinoma in Situ/diagnostic imaging/ethnology/*pathology ; China/ethnology ; Equipment Design ; Female ; Hong Kong ; Humans ; Mammography ; Minimally Invasive Surgical Procedures/instrumentation ; Sensitivity and Specificity ; Stereotaxic Techniques/instrumentation ; }, abstract = {BACKGROUND: Screening for breast cancer has resulted in an increasing number of mammographically detected lesions that require further management. The Advanced Breast Biopsy Instrumentation system is a recently added biopsy technique for the management of such lesions. The present paper will review the authors' experience in the use of this procedure in Chinese patients whose breast volume was smaller than that of Caucasians.

METHODS: Ninety-three patients were listed for the procedure and 78 (84%) underwent the procedure successfully. Ninety-two lesions were biopsied. Advanced Breast Biopsy Instrumentation (ABBI) was performed for clustered microcalcifications or abnormal mass/density. Minimally Invasive Breast Biopsy (MIBB), a suction-assisted core biopsy device, was employed for more scattered lesions. For small volume breasts, it may be required to bring the hand through the aperture to get the targeted lesions onto the digital image or, in the case of ABBI, to excise just beyond the deep margin of the lesion rather than the recommended depth.

RESULTS: The ABBI was performed for 43 (46.7%) lesions and MIBB for 49 (53.3%) lesions. Nine (9.8%) were diagnosed to have ductal carcinoma in situ, two (2.2%) had ductal carcinoma in situ with microinvasion and eight (8.7%) had invasive ductal carcinoma. All the malignant lesions required further management. In addition, 19 (20.7%) were found to have atypical hyperplasia. Patients' satisfaction and cosmetic outcome are good.

CONCLUSION: The ABBI and MIBB procedures can be applied satisfactorily for biopsy of mammographic lesions with good -cosmetic outcome in Chinese patients.}, } @article {pmid12534227, year = {2002}, author = {Volchenko, NN and Medovyĭ, VS and Slavnova, EN and Savostikova, MV and Medovyĭ, VS and Sokolinskiĭ, BZ and Klimova, NV}, title = {[A comparative morphometric analysis of cytograms of invasive ductal and invasive lobular breast cancer].}, journal = {Arkhiv patologii}, volume = {64}, number = {6}, pages = {37-39}, pmid = {12534227}, issn = {0004-1955}, mesh = {Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Lobular/diagnosis/*pathology ; Diagnosis, Differential ; Female ; Humans ; Image Cytometry ; Image Processing, Computer-Assisted ; }, abstract = {The most informative for differential diagnosis parameters (surface and nucleus polarization) were determined on the basis of morphometric analysis of 42 cytograms of invasive duct cancer (IDC) and 39 cytograms of invasive lobular breast cancer (ILC) using the computer analyzer MEKOC-C. Combination of these two parameters allowed the authors to elaborate a decisive rule for differential diagnosis of these two cancers (the mistake is reduced to 8.6%). The analysis of 8 informative morphometric nuclear parameters has shown that in ILC the nuclei are more monomorphic, less in square and perimeter, nucleoli are less numerous than in IDC. The study gives objective criteria for preoperative differential cytological diagnosis between IDC and ILC.}, } @article {pmid12532908, year = {2002}, author = {Mrhalová, M and Kodet, R and Strnad, P}, title = {[Invasive ductal carcinoma of the breast: study of the number of copies of the CCND1 gene and chromosome 11 using fluorescence in situ hybridization (FISH) in comparison with expression of cyclin D1 protein and estrogen receptors (ER alpha) with immunohistochemical detection].}, journal = {Casopis lekaru ceskych}, volume = {141}, number = {22}, pages = {708-714}, pmid = {12532908}, issn = {0008-7335}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Breast Neoplasms, Male/genetics ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Chromosomes, Human, Pair 11/*genetics ; Cyclin D1/*genetics/metabolism ; Estrogen Receptor alpha ; Female ; *Gene Amplification ; Humans ; *In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Receptors, Estrogen/*analysis ; }, abstract = {BACKGROUND: Overexpression of oncogenic proteins may be caused by gene amplifications. Cyclin D1 participates in regulation of the cell cycle. Relations between cyclin D1 expression and amplification of CCND1 gene encoding this protein in invasive duct breast carcinomas (IDC) are not fully elucidated. An increased interest is also focused on relations to the estrogen receptor (ER alpha).

METHODS AND RESULTS: We investigated copy numbers of the CCND1 gene, expression of cyclin D1 and expression of ER alpha in a group of 60 females and 1 male with IDC. The age range varied from 33 to 89 years (median 57 years). The number of CCND1 gene copies and the number of chromosome 11 was evaluated using FISH, the expression of cyclin D1 and ER alpha was investigated by IHC. We detected a strong amplification of CCND1 gene (> 10 copies per tumor cell nuclei) in 9 patients, weak amplification (< or = copies) in 16 patients. Amplification of the CCND1 gene correlated well with the overexpression of cyclin D1. We observed the overexpression of cyclin D1 also in 13 of 36 patients without the gene amplification; therefore, the mechanism of the protein overexpression is different than that caused by the gene amplification in a proportion of patients. Amplification of the CCND1 gene was associated with a high histologic grade of IDC, whereas cases with cyclin D1 overexpression only were not. 24 of 31 patients with overexpression of cyclin D1 coexpressed ER alpha. We did not find correlation between expression/amplification of cyclin D1/CCND1 gene and the size of carcinomas and with metastases to the axillary lymph nodes.

CONCLUSIONS: Amplification of the CCND1 gene is associated with overexpression of cyclin D1 in a majority of IDC. Overexpression of cyclin D1 is related to an increased expression of ER alpha. Interaction between cyclin D1 and ER alpha may explain low response to anti-estrogen therapy of some patients.}, } @article {pmid12530044, year = {2002}, author = {Watermann, DO and Einert, A and Ehritt-Braun, C and Hasenburg, A and Kieback, DG}, title = {Experience with the Advanced Breast Biopsy Instrumentation (ABBI) system.}, journal = {Anticancer research}, volume = {22}, number = {5}, pages = {3067-3070}, pmid = {12530044}, issn = {0250-7005}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/instrumentation/*methods ; Breast Neoplasms/*pathology/*surgery ; Carcinoma in Situ/pathology/surgery ; Carcinoma, Ductal, Breast/pathology/surgery ; Carcinoma, Lobular/pathology/surgery ; Female ; Humans ; Middle Aged ; Stereotaxic Techniques/instrumentation ; }, abstract = {BACKGROUND: The Advanced Breast Biopsy Instrumentation (ABBI) System is designed to excise nonpalpable breast lesions under stereotactic control. We report our experience with special regard to the histological evaluation of margins.

PATIENTS AND METHODS: Breast biopsies using the ABBI system were performed on 101 patients with microcalcifications. In histologically-proven breast cancer, a re-excision was performed.

RESULTS: Malignant lesions were found in thirteen patients (3 CLIS, 5 DCIS, 5 invasive ductal carcinoma). The margins were positive in two specimens with DCIS. In subsequent lumpectomies one patient with invasive cancer had residual intraductal cancer. All the patients with DCIS had residual cancer, even those with negative margins of the ABBI-specimen. Only minor complications were observed with the ABBI procedure.

CONCLUSION: The ABBI system is a safe, minimally invasive stereotactic breast biopsy technique. It saves open biopsies in atypical hyperplasia and CLIS. In cases of DCIS or invasive cancer re-excision is inevitable.}, } @article {pmid12530033, year = {2002}, author = {Ikpatt, OF and Kuopio, T and Ndoma-Egba, R and Collan, Y}, title = {Breast cancer in Nigeria and Finland: epidemiological, clinical and histological comparison.}, journal = {Anticancer research}, volume = {22}, number = {5}, pages = {3005-3012}, pmid = {12530033}, issn = {0250-7005}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/*pathology ; Carcinoma, Ductal, Breast/*epidemiology/*pathology ; Female ; Finland/epidemiology ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Neoplasm Staging ; Nigeria/epidemiology ; Parity ; Survival Rate ; }, abstract = {BACKGROUND: We compared the histology and patterns of occurrence of breast cancers in Nigeria (n = 297) and Finland (n = 285).

PATIENTS AND METHODS: The histology of invasive ductal carcinoma (IDC) was re-evaluated using similar criteria. The clinical data were extracted from medical records.

RESULTS: The mean age at presentation was 42.7 (12.2) years in Nigeria vs. 58.7 (12.5) years in Finland. In both populations there was an association between reproductive factors and the occurrence of breast cancer. In Nigeria, 53.2% of cases belonged to stages 3 and 4 (vs. 6.7% in Finland). In Finland there were higher frequencies of lobular, tubular and mucinous types than in Nigeria. The Nigerian material had more medullary type (2.7% vs. 0.7% in Finland), extensive necrosis, nuclear atypia and pleomorphism, with coexisting pleomorphic ductal carcinoma in situ. At 2 years after treatment, the survival figures for Nigeria and Finland were 72.8% and 96.4%, respectively.

CONCLUSION: The histology of Nigerian and Finnish cancers clearly differ. Nigerian cancers appear more advanced with higher grade. The atypical in situ component is clearly more common in Nigeria. Part of the differences can be explained by diagnostic and treatment delays associated with misguided socio-cultural beliefs, poor health care access and impaired immunity.}, } @article {pmid12525766, year = {2003}, author = {Zhang, Z and Yamashita, H and Toyama, T and Omoto, Y and Sugiura, H and Hara, Y and Haruki, N and Kobayashi, S and Iwase, H}, title = {Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {10}, number = {1}, pages = {70-73}, doi = {10.1007/BF02967628}, pmid = {12525766}, issn = {1340-6868}, mesh = {Adult ; Aged ; Asian People/*genetics ; Breast Diseases/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/genetics ; Carcinoma, Intraductal, Noninfiltrating/genetics ; Female ; Humans ; Japan ; Middle Aged ; *Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Precancerous Conditions/genetics ; Receptors, Estrogen/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha.

METHODS: To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and cancer cells of DCIS were microdissected. We also performed direct sequencing analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of benign breast tumors, 11 cases of DCIS and 20 cases of IDC.

RESULTS: No A908G mutation was found in the ER alpha gene in these breast lesions.

CONCLUSION: This mutation might be absent or occur in so few cells as to be undetectable by PCR-RFLP or direct sequencing.}, } @article {pmid12519301, year = {2003}, author = {Kikuchi, K and Yanagawa, Y and Aranami, T and Iwabuchi, C and Iwabuchi, K and Onoé, K}, title = {Tumour necrosis factor-alpha but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation.}, journal = {Immunology}, volume = {108}, number = {1}, pages = {42-49}, pmid = {12519301}, issn = {0019-2805}, mesh = {Animals ; Cell Culture Techniques ; Cell Differentiation/immunology ; Cell Line ; Dendritic Cells/cytology/*immunology ; Dose-Response Relationship, Immunologic ; Immunophenotyping ; Interleukin-12/biosynthesis ; Lipopolysaccharides/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Th1 Cells/immunology ; Th2 Cells/*immunology ; Tumor Necrosis Factor-alpha/*immunology ; }, abstract = {Using murine spleen-derived dendritic cells (DC) and DO11.10 T cells specific for ovalbumin (OVA), the influences of maturational condition and antigen dose on the capability of DC to induce helper T-cell (Th) differentiation were analysed. Immature DC (iDC) with high- or low-dose OVA(323-339) predominantly induced Th1 or Th2 responses in DO11.10 T cells, respectively. DC matured by tumour necrosis factor-alpha (TNF/DC) induced a significantly higher Th2 response in the presence of low-dose OVA(323-339) than iDC and DC matured by lipopolysaccharide (LPS) (LPS/DC). In the presence of high-dose OVA(323-339), LPS/DC induced significantly lower levels of Th1 response than iDC. Under these conditions no difference in the Th1 response was noted between TNF/DC and iDC. The enhanced capability of TNF/DC with a low-dose antigen for Th2 polarization and the decreased preference of LPS/DC with a high-dose antigen to Th1 polarization were not related to the amount of IL-12 produced in these cultures. These results demonstrate for the first time that TNF/DC with a low-dose antigen are potent inducers of Th2 differentiation.}, } @article {pmid12516960, year = {2002}, author = {Grimshaw, MJ and Naylor, S and Balkwill, FR}, title = {Endothelin-2 is a hypoxia-induced autocrine survival factor for breast tumor cells.}, journal = {Molecular cancer therapeutics}, volume = {1}, number = {14}, pages = {1273-1281}, pmid = {12516960}, issn = {1535-7163}, mesh = {Antihypertensive Agents/pharmacology ; Blotting, Northern ; Breast Neoplasms/*metabolism/*pathology ; Cell Survival ; DNA-Binding Proteins/metabolism ; Dose-Response Relationship, Drug ; Endothelin-2/*metabolism ; Female ; Humans ; *Hypoxia ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Necrosis ; Nuclear Proteins/metabolism ; Oligopeptides/pharmacology ; Ovarian Neoplasms/metabolism/pathology ; Peptides, Cyclic/pharmacology ; Piperidines/pharmacology ; RNA, Messenger/metabolism ; Receptor, Endothelin B ; Receptors, Endothelin/metabolism ; Time Factors ; *Transcription Factors ; Tumor Cells, Cultured ; Up-Regulation ; }, abstract = {Endothelins (ETs) are a group of vasoactive peptides (ET-1, ET-2 and ET-3) produced by many cell types that bind to G-protein-linked transmembrane receptors, ET-A receptors (ET-RAs) and ET-B receptors (ET-RBs). These peptides are expressed in several human tumors, including carcinomas of the breast, and have a mitogenic effect in ovarian cancer cell lines. We investigated ET expression in infiltrating ductal carcinomas (IDCs) of the breast and the relationship between ET and hypoxia. ET staining was increased in human grade II IDC samples compared with normal breast tissue. ET-2 and ET-RB mRNA expression were absent in the majority of normal human breast samples (1 of 5 and 0 of 5, respectively) but was present in the majority of IDC tested (13 of 15 and 12 of 15, respectively). In a murine breast cancer model, HTH-K, ET-2, and ET-RB mRNA were detected in tumor but not normal breast tissue, and ET expression colocalized with areas of hypoxia. In vitro, ET-2, ET-RA, and ET-RB mRNA were increased by incubating HTH-K cells in hypoxia (0.1% oxygen) for 24 h. Hypoxia also up-regulated ET-2 mRNA in several human breast tumor cell lines. ET-2 mRNA increased within 3 h in a hypoxia-inducible factor 1-dependent manner. The ET-RB antagonist BQ-788 increased in hypoxia-associated apoptosis of breast tumor cells in vitro. These effects could be reversed by addition of ET-2 peptide. Intratumoral injection of BQ-788 led to an increase in the development and extent of necrosis within the HTH-K tumor and a decrease in the rate of tumor growth. The ET-RA antagonist, BQ-123, also led to a decrease in tumor growth but without a concomitant increase in necrosis. We propose that modulation of ET-2 production via the hypoxia-inducible factor 1 transcription factor and autocrine signaling via ET-RB is a novel mechanism by which tumor cells can withstand hypoxic stress. Treatment of breast carcinomas with ET receptor antagonists may have a therapeutic benefit.}, } @article {pmid12506168, year = {2003}, author = {Hoogerbrugge, N and Bult, P and de Widt-Levert, LM and Beex, LV and Kiemeney, LA and Ligtenberg, MJ and Massuger, LF and Boetes, C and Manders, P and Brunner, HG}, title = {High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {21}, number = {1}, pages = {41-45}, doi = {10.1200/JCO.2003.02.137}, pmid = {12506168}, issn = {0732-183X}, mesh = {Adult ; Age Distribution ; Breast Neoplasms/*epidemiology/*genetics/pathology/prevention & control ; Carcinoma in Situ/epidemiology/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/genetics/pathology ; Female ; *Genetic Predisposition to Disease ; Humans ; Hyperplasia/epidemiology/genetics/pathology ; Mastectomy ; Middle Aged ; Multivariate Analysis ; Precancerous Conditions/*epidemiology/*genetics/pathology ; Prevalence ; Prospective Studies ; ROC Curve ; Risk ; }, abstract = {PURPOSE: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy.

PATIENTS AND METHODS: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area.

RESULTS: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P =.01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02).

CONCLUSION: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.}, } @article {pmid12493023, year = {2003}, author = {Kim, DH and Yoon, DS and Dooley, WC and Nam, ES and Ryu, JW and Jung, KC and Park, HR and Sohn, JH and Shin, HS and Park, YE}, title = {Association of maspin expression with the high histological grade and lymphocyte-rich stroma in early-stage breast cancer.}, journal = {Histopathology}, volume = {42}, number = {1}, pages = {37-42}, doi = {10.1046/j.1365-2559.2003.01567.x}, pmid = {12493023}, issn = {0309-0167}, mesh = {Adenocarcinoma/*metabolism/mortality/pathology ; Biomarkers, Tumor/metabolism ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Lobular/metabolism/pathology ; Cell Count ; Disease-Free Survival ; Female ; *Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Lymphocytes/metabolism/pathology ; Neoplasm Staging ; Proteins/*metabolism ; Serine Proteinase Inhibitors/*metabolism ; Serpins/*metabolism ; Stromal Cells/metabolism/pathology ; Survival Rate ; }, abstract = {AIMS: Maspin is a recently described member of the serpin family or protease inhibitors that is known to be a tumour suppressor gene product. Loss of maspin expression has been found in most breast cancer cases and is correlated with cell motility and tumour invasiveness. However, its precise role in human breast cancer remains to be discovered. We aimed to evaluate the role of maspin in early-stage breast cancer.

METHODS AND RESULTS: We analysed the expression of maspin in 192 stage I and II primary breast cancers by immunohistochemistry. Of these cases, 34.4% showed maspin expression. Maspin expression was more frequently found in invasive ductal carcinoma (36.4%) than in invasive lobular carcinoma (7.1%). High maspin expression was demonstrated in breast cancers showing high histological grade or lymphocyte-rich stroma (P < 0.05). Maspin expression was not associated with overall and disease-free survival rate of breast cancer.

CONCLUSIONS: The results indicate that different biological mechanisms may be responsible for maspin expression in histologically distinct types of breast cancer. Our survey suggests that maspin expression in breast cancer might have a compensatory role rather than prognostic one.}, } @article {pmid12493022, year = {2003}, author = {Matsukita, S and Nomoto, M and Kitajima, S and Tanaka, S and Goto, M and Irimura, T and Kim, YS and Sato, E and Yonezawa, S}, title = {Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast: comparison with invasive ductal carcinoma.}, journal = {Histopathology}, volume = {42}, number = {1}, pages = {26-36}, doi = {10.1046/j.1365-2559.2003.01530.x}, pmid = {12493022}, issn = {0309-0167}, support = {CA 24321/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/*metabolism/pathology ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Mucin 5AC ; Mucin-1/metabolism ; Mucin-2 ; Mucin-6 ; Mucins/classification/*metabolism ; }, abstract = {AIMS: Mucinous carcinoma of the breast usually shows less frequent lymph node metastasis and more favourable outcome compared with invasive ductal carcinoma. The aim of this study is to compare the expression profiles of several mucins in mucinous carcinomas and invasive ductal carcinomas to gain insight into the relationship between the less aggressive biological nature of mucinous carcinoma and the role of mucins.

METHODS AND RESULTS: We examined the expression profiles of MUC1 (membrane-bound mucin) of different glycoforms (from non-glycosylated form to fully glycosylated form), MUC2 (intestinal type secretory mucin), MUC5AC (gastric surface type secretory mucin) and MUC6 (gastric pyloric gland type secretory mucin) in 17 mucinous carcinomas and 46 invasive ductal carcinomas using immunohistochemistry. Various glycoforms of MUC1 were expressed frequently in both mucinous carcinomas (65-100%) and invasive ductal carcinomas (92-100%), although non-glycosylated MUC1 (MUC1/CORE) and fully glycosylated MUC1 (MUC1/HMFG-1) showed significantly lower expression rates in mucinous carcinomas compared with those in invasive ductal carcinomas. The expression rates of MUC2 (94%) and MUC6 (71%) in mucinous carcinomas were significantly higher than those of MUC2 (15%) and MUC6 (15%) in invasive ductal carcinomas. There was no significant difference in the expression rate of MUC5AC in mucinous carcinomas (12%) and that in invasive ductal carcinomas (4%).

CONCLUSIONS: The expression rate of MUC1/CORE and MUC1/HMFG-1, which is related to poor prognosis in the gastric and colorectal cancers, is low in mucinous carcinomas. The high expression rate of gel-forming secretory mucins (MUC2 and MUC6) in mucinous carcinoma suggests that high production of these types of mucins may act as a barrier to cancerous extension resulting in their less aggressive biological behaviour.}, } @article {pmid12490977, year = {2002}, author = {Rivera-Hueto, F and Hevia-Vázquez, A and Utrilla-Alcolea, JC and Galera-Davidson, H}, title = {Long-term prognosis of teenagers with breast cancer.}, journal = {International journal of surgical pathology}, volume = {10}, number = {4}, pages = {273-279}, doi = {10.1177/106689690201000405}, pmid = {12490977}, issn = {1066-8969}, mesh = {Adenocarcinoma/chemistry/epidemiology/*pathology/therapy ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/epidemiology/*pathology/therapy ; Child ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; Mastectomy ; Pregnancy ; Pregnancy Complications, Neoplastic ; Spain/epidemiology ; Treatment Outcome ; }, abstract = {We report 4 new cases of breast carcinoma in teenage girls diagnosed by use of histochemical and immunohistochemical methods. These cases of breast carcinoma in women under 20 years of age were found in the files of our department in the last 24 years (1976-2000). The patients had operable breast carcinomas corresponding to various histologic types (1 invasive ductal carcinoma associated with fibroadenoma, 2 secretory carcinomas, and 1 invasive lobular-type carcinoma). Simple mastectomy with low axillary lymph node dissection was performed in 2 postpubertal patients. Only 1 patient received adjuvant chemotherapy (case 4). After follow-up ranging from 76 to 126 months, 3 patients are alive and disease-free and 1 has disseminated metastatic disease. The correlations with prognosis-related risk factors (stage, age, previous benign lesions, family history, histologic types, hormonal receptors, and pregnancy) were examined.}, } @article {pmid12488758, year = {2002}, author = {Kinoshita, T and Yashiro, N and Ihara, N and Funatu, H and Fukuma, E and Narita, M}, title = {Diffusion-weighted half-Fourier single-shot turbo spin echo imaging in breast tumors: differentiation of invasive ductal carcinoma from fibroadenoma.}, journal = {Journal of computer assisted tomography}, volume = {26}, number = {6}, pages = {1042-1046}, doi = {10.1097/00004728-200211000-00033}, pmid = {12488758}, issn = {0363-8715}, mesh = {Adult ; Aged ; Artifacts ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Diagnosis, Differential ; Female ; Fibroadenoma/diagnosis/*pathology ; Fourier Analysis ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Middle Aged ; }, abstract = {PURPOSE: The purpose of this investigation is to evaluate the usefulness of diffusion-weighted half-Fourier single-shot turbo spin echo (DW-HASTE) imaging in differentiating invasive ductal carcinoma from fibroadenoma.

METHOD: The DW-HASTE imaging was performed in patients with invasive ductal carcinoma (n = 16) and fibroadenoma (n = 6). Images were obtained with diffusion-sensitizing gradients of 0 and 700 mm(2)/s. The apparent diffusion coefficient (ADC) was calculated.

RESULTS: The DW-HASTE imaging was not affected with susceptibility and chemical shift artifacts usually present in DW echo planar imaging. The DW-HASTE imaging had low tumor detectability (62%), however. The difference in mean ADC of invasive ductal carcinoma (1.216 +/- 0.189 x 10(-3)mm(2)/s) and fibroadenoma (1.495 +/- 0.181 x 10(-3)mm(2)/s) was statistically significant.

CONCLUSION: Apparent diffusion coefficient measurement using DW-HASTE imaging is helpful in differentiating invasive ductal carcinoma from fibroadenoma. Nevertheless, DW-HASTE imaging has low detectability at present; therefore, more technologic improvement is desired.}, } @article {pmid12486098, year = {2002}, author = {Verbovetski, I and Bychkov, H and Trahtemberg, U and Shapira, I and Hareuveni, M and Ben-Tal, O and Kutikov, I and Gill, O and Mevorach, D}, title = {Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7.}, journal = {The Journal of experimental medicine}, volume = {196}, number = {12}, pages = {1553-1561}, pmid = {12486098}, issn = {0022-1007}, mesh = {Antigens, CD/immunology/*metabolism ; *Apoptosis ; B7-2 Antigen ; Complement C3b/*immunology ; Complement System Proteins/immunology/metabolism ; Dendritic Cells/*immunology ; Down-Regulation ; Genes, MHC Class II ; HLA-DR Antigens/*metabolism ; Humans ; Integrin alphaXbeta2/metabolism ; Jurkat Cells ; Macrophage-1 Antigen/metabolism ; Membrane Glycoproteins/*metabolism ; Opsonin Proteins/*immunology ; Receptors, CCR7 ; Receptors, Chemokine/*metabolism ; Up-Regulation ; }, abstract = {Immature dendritic cells (iDCs) do not mature after uptake of apoptotic cells and may play a role in the induction of peripheral tolerance to self antigens derived from apoptotic material. The integrins, alphavbeta3, alphavbeta5, and the scavenger receptor, CD36, have been shown to mediate uptake of apoptotic cells by iDCs. However, it is not known whether the complement system, also takes part in this process. In this study we investigated the ability of iDCs to bind to apoptotic cells opsonized by iC3b. Monocyte-derived dendritic cells were offered apoptotic Jurkat cells opsonized by autologous iC3b and labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate. A significant increase (P < 0.001) in the amount of cleared apoptotic cells was seen at low ratios. Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and beta2-integrins (P < 0.001), and up-regulated expression of CCR7 (P < 0.001). In addition, iDC maturation responses to CD40L and lipopolysaccharide were significantly inhibited. We conclude that opsonization of apoptotic cells by iC3b induces tolerant iDCs that are able to migrate to lymph nodes.}, } @article {pmid12485722, year = {2003}, author = {Nakashima, K and Yamamoto, K and Al-Dirbashi, OY and Kaddoumi, A and Nakashima, MN}, title = {Semi-micro column HPLC of triazolam in rat plasma and brain microdialysate and its application to drug interaction study with itraconazole.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {30}, number = {6}, pages = {1809-1816}, doi = {10.1016/s0731-7085(02)00523-x}, pmid = {12485722}, issn = {0731-7085}, mesh = {Animals ; Chromatography, High Pressure Liquid/methods ; Drug Interactions/physiology ; Itraconazole/blood/*metabolism ; Male ; Microdialysis/*methods ; Rats ; Rats, Wistar ; Triazolam/blood/*metabolism ; }, abstract = {Semi-micro column high-performance liquid chromatographic method with ultraviolet detection for the determination of triazolam (TZ) in rat plasma and brain microdialysate is described. The separation was achieved on a 250 x 1.5 mm, i.d. C(18) column and the column effluent was monitored at 222 nm. The detection limits at a signal-to-noise ratio of 3 obtained using spiked plasma and artificial cerebrospinal fluid were 2.1 and 0.7 ng/ml, respectively. The method was applied to drug-drug interaction study of TZ with itraconazole (ITZ). The peak concentration (C(max)) and the area under the curve (AUC) of TZ in brain microdialysate after simultaneous administration of TZ (2.5 mg/kg, intravenously (i.v.)) and ITZ (25 mg/kg, p.o.) to rats increased 3.4-folds (P<0.001) and 2.9-folds (P<0.001), respectively, compared to those of TZ alone. Also, the AUC of TZ in plasma increased 2.6-folds and remarkable delay in its elimination half-life (t(1/2)) was observed. The concentrations of TZ in brain microdialysate and plasma were also measured after single administration of TZ (2.5 mg/kg, i.v.) to rats pretreated with daily administration of ITZ (25 mg/kg, p.o.) once a day for a week. There was no significant difference in TZ's C(max) in both ITZ treatments (P>0.2) however its t(1/2) after the daily pretreatment with ITZ was significantly increased (P<0.05). In plasma, the AUC of TZ after daily pretreatment of ITZ was lower than the single combined treatment, but significantly different from TZ's AUC in the absence of ITZ (P<0.05). As a result, single simultaneous administration of TZ with ITZ and single administration of TZ after daily pretreatment with ITZ to rats, ITZ seriously interfered with the pharmacokinetic parameters of TZ in plasma and brain micodialysate.}, } @article {pmid12481013, year = {2002}, author = {Latta, EK and Tjan, S and Parkes, RK and O'Malley, FP}, title = {The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {12}, pages = {1318-1325}, doi = {10.1097/01.MP.0000038462.62634.B1}, pmid = {12481013}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Invasiveness ; Receptor, ErbB-2/biosynthesis/*genetics ; }, abstract = {HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast.}, } @article {pmid12475464, year = {2002}, author = {Fauchier, L and Marie, O and Casset-Senon, D and Babuty, D and Cosnay, P and Fauchier, JP}, title = {Interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy: a prognostic study with fourier phase analysis of radionuclide angioscintigraphy.}, journal = {Journal of the American College of Cardiology}, volume = {40}, number = {11}, pages = {2022-2030}, doi = {10.1016/s0735-1097(02)02569-x}, pmid = {12475464}, issn = {0735-1097}, mesh = {Adult ; Cardiomyopathy, Dilated/diagnosis/*etiology/*physiopathology ; Electrocardiography ; Female ; Follow-Up Studies ; Gated Blood-Pool Imaging ; Heart Ventricles/diagnostic imaging/physiopathology ; Hemodynamics/physiology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Severity of Illness Index ; Statistics as Topic ; Time Factors ; Ventricular Dysfunction/diagnosis/*etiology/*physiopathology ; }, abstract = {OBJECTIVES: The study evaluated the prognostic value of interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy (IDC).

BACKGROUND: Biventricular pacing is an emerging treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. The prognostic values of interventricular and intraventricular dyssynchrony have not been previously compared.

METHODS: A total of 103 patients with IDC were studied. Left bundle branch block was present in 25% of patients. Equilibrium radionuclide angiography was performed and Fourier phase analyses were examined in both ventricles. Difference between the mean phase of left ventricle (LV) and right ventricle (RV) assessed interventricular dyssynchrony, and standard deviations (SDs) of the mean phase in each ventricle assessed intraventricular dyssynchrony.

RESULTS: The QRS duration was related to both interventricular and intraventricular dyssynchrony. A degradation of the hemodynamic status was associated with an increase in intraventricular dyssynchrony but not in interventricular dyssynchrony. With a follow-up of 27 +/- 23 months, 18 patients had a major cardiac event (7 cardiac deaths; 11 worsening, leading to heart transplantation). The SDs of the LV and RV mean phase and QRS duration were predictors of cardiac event (all p < 0.0001), but interventricular dyssynchrony was not. Among 13 univariate predictors of cardiac event, the only independent predictors were an increased SD of LV mean phase (p = 0.0004) and an increased pulmonary capillary wedge pressure (p = 0.009).

CONCLUSIONS: Intraventricular dyssynchrony evaluated with phase analysis of radionuclide angiography is an independent predictor of cardiac event in IDC. The prognosis is related to intraventricular rather than to interventricular dyssynchrony in IDC.}, } @article {pmid12469156, year = {2003}, author = {Yang, Q and Sakurai, T and Yoshimura, G and Suzuma, T and Umemura, T and Nakamura, M and Nakamura, Y and Mori, I and Kakudo, K}, title = {Prognostic value of Bcl-2 in invasive breast cancer receiving chemotherapy and endocrine therapy.}, journal = {Oncology reports}, volume = {10}, number = {1}, pages = {121-125}, pmid = {12469156}, issn = {1021-335X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy/*metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/*metabolism/pathology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Epirubicin ; Female ; Fluorouracil ; Humans ; Ki-67 Antigen/metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Receptors, Estrogen/metabolism ; Survival Rate ; Tamoxifen ; }, abstract = {Apoptosis induced by anticancer agents is a mechanism of treatment activity, overexpression of antiapoptotic genes could produce drug resistant tumors. We have demonstrated that the susceptibility of Bcl-2-negative tumors to a series of anticancer drugs was significantly higher than that of Bcl-2-positive tumors. The purpose of this study was to examine if negative Bcl-2 expression has treatment benefit in breast cancer patients received chemotherapy and endocrine treatment. A cohort of 147 Japanese women with invasive ductal carcinoma was studied. All the patients received postoperative adjuvant therapy consisting of combination chemotherapy with cyclophosphamide, epirubicin, and fluorouracil, and tamoxifen therapy. The expression of Bcl-2, estrogen receptor (ER) and MIB-1 was evaluated in breast cancer surgical specimens. Bcl-2 immunostaining was inversely correlated with increasing histologic grade (p=0.0095) and MIB-1 (p=0.0128). Furthermore, a positive correlation between Bcl-2 and ER was observed (p<0.0001). Unexpectedly, survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that Bcl-2-positivity was associated with favorable prognosis (p=0.0430). Cox proportional hazard model demonstrated that positive Bcl-2 expression still has favorable survival (p=0.0242) after consideration of other prognostic factors. Our results imply that Bcl-2 is a significant favorable prognostic factor for breast cancer with chemotherapy and endocrine therapy.}, } @article {pmid12465329, year = {2002}, author = {Baier, V and Leder, U and Voss, A}, title = {[Effect of post-extrasystole potentiation on blood pressure and heart rate regulation].}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {47 Suppl 1 Pt 2}, number = {}, pages = {871-874}, doi = {10.1515/bmte.2002.47.s1b.871}, pmid = {12465329}, issn = {0013-5585}, mesh = {Baroreflex/physiology ; Blood Pressure/*physiology ; Blood Pressure Monitoring, Ambulatory/*instrumentation ; Cardiac Complexes, Premature/*physiopathology ; Cardiomyopathy, Dilated/*physiopathology ; Electrocardiography, Ambulatory/*instrumentation ; Heart Rate/*physiology ; Humans ; Reference Values ; Signal Processing, Computer-Assisted/*instrumentation ; }, abstract = {Noninvasive finger arterial blood pressure and ECG were recorded for 30 min in patients with idiopathic dilated cardiomyopathy (IDC) and healthy control subjects (CON) for the investigation of blood pressure and heart rate regulation following a premature ventricular complex (PVC). The potentiation of blood pressure amplitude of the postextrasystolic beat was fivefold increased in IDC compared with CON (48.7 +/- 32.6% vs. 9.8 +/- 5.4%, p < 0.01). PVC starts a baroreflex response, which last about 10 s in physiological regulation. In contrast, the baroreflex response in IDC is immediately suppressed by the augmented potentiation of the blood pressure amplitude from the first postextrasystolic beat. Thus, the regulation after PVC is determined by the PVC itself and postextrasystic potentiation.}, } @article {pmid12463710, year = {2002}, author = {Jmor, S and Al-Sayer, H and Heys, SD and Payne, S and Miller, I and Ah-See, A and Hutcheon, A and Eremin, O}, title = {Breast cancer in women aged 35 and under: prognosis and survival.}, journal = {Journal of the Royal College of Surgeons of Edinburgh}, volume = {47}, number = {5}, pages = {693-699}, pmid = {12463710}, issn = {0035-8835}, mesh = {Adult ; Breast/pathology ; Breast Neoplasms/epidemiology/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/epidemiology/mortality/pathology/therapy ; Combined Modality Therapy ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Breast cancer comprises 22% of all cancers occurring in females but only 2% of cases occur in women aged 35 years and less. The presentation, behaviour and prognosis of breast cancer in such women, when compared with older women, are unclear and conflicting results have been reported. This study has audited clinical and pathological features in patients aged 35 years and under with breast cancer.

METHODS: One hundred and thirteen patients were identified. The details of clinical staging, local and distant disease recurrence and overall survival were obtained for all patients. Histological sections of tumours were examined for type, grade, size, presence of surrounding intraductal carcinoma, presence of vascular space invasion, lymph node involvement and oestrogen receptor (ER) status.

RESULTS: Histological examination of the tumours revealed that 94% were invasive ductal carcinoma. In 73% of the cases the tumours were grade 3, 49% of patients who underwent axillary surgery had lymph node involvement and 20% of tumours expressed ERs. The overall 5-year survival was 64%. Predictors of a poorer survival (univariate analysis) were: increasing tumour size, absence of ERs, presence of lymphovascular space invasion, axillary lymph node involvement and detectable metastases at the initial presentation. Multivariate analysis revealed that only lymphovascular space invasion was an independent predictor of a poor survival.

CONCLUSION: Breast cancer in young (< or = 35 years) women is biologically aggressive, compared with older women. Factors predicting survival and overall survival rates, however, were comparable with those previously reported for older women with breast cancer.}, } @article {pmid12461672, year = {2002}, author = {Livesey, G}, title = {Thermogenesis associated with fermentable carbohydrate in humans, validity of indirect calorimetry, and implications of dietary thermogenesis for energy requirements, food energy and body weight.}, journal = {International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity}, volume = {26}, number = {12}, pages = {1553-1569}, doi = {10.1038/sj.ijo.0802168}, pmid = {12461672}, mesh = {Body Weight/*physiology ; Calorimetry, Indirect/*standards ; Cross-Over Studies ; Dietary Carbohydrates/*metabolism ; Energy Intake/physiology ; Female ; Fermentation/physiology ; Humans ; Middle Aged ; Randomized Controlled Trials as Topic ; Terminology as Topic ; Thermogenesis/*physiology ; }, abstract = {BACKGROUND: Animal studies and theory show fermentable carbohydrate (FC) intake causes appreciably thermogenesis, but a similar occurrence in humans is controversial.

HYPOTHESES: (a) That indirect calorimetry (IDC) is a valid method to assess thermogenesis during fermentation. (b) That a consistent and rigorous approach to the analysis of published IDC data from human studies will establish a representative thermogenic response to FC. (c) That conventional estimates of food energy and energy requirements can mismatch appreciably, more especially when thermogenesis is ignored.

PURPOSE: To derive information and understanding of IDC, thermogenesis and energy balance in relation to food energy and energy requirement estimates.

METHODS: (a) The validities of IDC equations that estimate the heat of reaction and carbohydrate utilization were assessed for various types of FCs under various circumstances. (b) Pooled analysis of eight published randomized cross-over studies in humans with elevation of FC intake. Studies were analysed for the first time or reanalysed according to a consistent approach with appropriate corrections for confounders. (c) Some 1500 regular and 'special' diet compositions were examined to assess the extent to which Atwater general food energy factors and updated estimates of energy requirements mismatch due to variation in substrate-associated thermogenesis and substrate-associated faecal+urinary energy losses. Impact of such mismatches on BMI was assessed under conditions of all else being equal.

RESULTS: (a) Indirect calorimetry was valid, providing robust estimates of heat production during various types of fermentation; only small correction factors were necessary. By contrast, IDC equations for carbohydrate utilization sometimes applied poorly to FC. (b) A best estimate of thermogenesis in humans due to fermentation, above that due to oral glucose as a reference standard, was 0.39 (s.e.m. 0.14) kJ per kJ net metabolizable energy (NME; P<0.05, n=8 studies, total 72 humans) compared with 0.34 kJ/kJ from theory. Six sources of bias were identified; all had potential to underestimate FC thermogenesis. (c) Mismatches in energy availability and requirement estimates were often marked and translated into long-term differences in body mass index from approximately 20 to 33 kg/m(2) in average-height middle-aged initially obese women, and from approximately 22 to a non-survivable 13 kg/m(2) in initially slim women.

CONCLUSIONS: (a) Indirect calorimetry is valid for the present purpose. (b) Thermogenesis in response to FC is real in humans and is comparable to that in animals and in theory. (c) Mismatches between estimates of energy requirements and dietary energy as metabolizable energy means the two expressions are not directly comparable, which has implications for the expression of food energy, energy requirements and the conduct and interpretation of research related to body weight.}, } @article {pmid12461063, year = {2002}, author = {Reis-Filho, JS and Milanezi, F and Amendoeira, I and Albergaria, A and Schmitt, FC}, title = {p63 Staining of myoepithelial cells in breast fine needle aspirates: a study of its role in differentiating in situ from invasive ductal carcinomas of the breast.}, journal = {Journal of clinical pathology}, volume = {55}, number = {12}, pages = {936-939}, pmid = {12461063}, issn = {0021-9746}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology ; DNA-Binding Proteins ; Diagnosis, Differential ; Female ; Genes, Tumor Suppressor ; Humans ; Immunoenzyme Techniques ; *Membrane Proteins ; Middle Aged ; Phosphoproteins/*analysis ; Retrospective Studies ; Trans-Activators/*analysis ; Transcription Factors ; Tumor Suppressor Proteins ; }, abstract = {AIMS: One of the limitations of fine needle aspiration biopsy (FNAB) of the breast is in distinguishing invasive carcinoma (IDC) from ductal carcinoma in situ (DCIS). It has been proposed that the presence of myoepithelial cells overlying epithelial malignant cell clusters suggests DCIS. However, the recognition of myoepithelial cells in aspirates may be difficult. The aim of this study was to investigate a new nuclear myoepithelial cell marker, p63, a p53 homologue nuclear transcription factor, in a series of breast FNABs in an attempt to distinguish IDC from DCIS.

METHODS: Papanicolaou stained smears from eight cases of pure DCIS and 15 cases of pure IDC with a histologically confirmed diagnosis were submitted to immunocytochemical analysis using the antibody 4A4 against p63. Two pathologists evaluated the presence of p63 positive cells overlying malignant cell clusters and admixed with malignant cells. The frequency of p63 positive cells in DCIS and IDC was compared using Fisher's exact test.

RESULTS: p63 consistently stained the nuclei of myoepithelial cells, either overlying malignant cell clusters and/or admixed with malignant cells. p63 positive myoepithelial cells were seen in all DCIS cases and in nine of the 15 cases of IDC (p = 0.0375). In eight cases (three DCIS and five IDC), scattered p63+ epithelial malignant cells were seen.

CONCLUSIONS: Although p63 positive myoepithelial cells are found more frequently in DCIS cases, their presence cannot be used as a criterion to rule out invasion in breast FNABs because they are present in up to 60% of invasive cases.}, } @article {pmid12455059, year = {2003}, author = {Hamanaka, Y and Suehiro, Y and Fukui, M and Shikichi, K and Imai, K and Hinoda, Y}, title = {Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer.}, journal = {International journal of cancer}, volume = {103}, number = {1}, pages = {97-100}, doi = {10.1002/ijc.10801}, pmid = {12455059}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Neoplasm/*blood ; Autoantibodies/*blood ; Carcinoma, Ductal, Breast/*immunology/mortality/pathology ; Female ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Mucin-1/*immunology ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*immunology/mortality/pathology ; Prognosis ; Survival Rate ; Transfection ; }, abstract = {MUC1 is immunogenic in vivo and humoral and cellular immune responses against MUC1 have been detected in cancer patients. Our study explored the association of circulating anti-MUC1 antibodies with clinicopathological parameters or patients' survival of pancreatic cancer. Serum specimens from 36 patients with invasive ductal carcinoma of the pancreas were subjected to enzyme immunoassay for anti-MUC1 IgG or IgM antibodies. Serum levels of anti-MUC1 IgG antibodies were significantly correlated with survival time (p = 0.0004), whereas neither those of anti-MUC1 IgM nor anti-Galalpha(1,3)Gal IgG antibodies, the latter known as natural antibodies cross-reactive with MUC1, showed a given tendency. Some patients' sera with the higher antibody titer showed the reactivity with MUC1-transfectants of cultured pancreatic cancer cells, but not with MUC1-negative parental cells. When the samples were tentatively divided into 2 groups by the serum level of anti-MUC1 IgG antibodies, the survival of patients was significantly longer in the group with optical density >or=0.3 than in that with optical density <0.3 (p = 0.008). Circulating anti-MUC1 IgG antibody levels remained significant (HR, 0.03; 95% CI, 0.003-0.289; p = 0.0024) after multivariate analysis for pTNM stage, patient age and gender. These data suggest that circulating anti-MUC1-IgG antibody levels may be predictive for survival of pancreatic cancer patients.}, } @article {pmid12452072, year = {2002}, author = {Zhao, P and Li, XY and Chen, LZ}, title = {[Loss of fragile histidine triad expression and metastasis in breast cancer].}, journal = {Ai zheng = Aizheng = Chinese journal of cancer}, volume = {21}, number = {6}, pages = {668-670}, pmid = {12452072}, mesh = {*Acid Anhydride Hydrolases ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Proteins/*biosynthesis ; Tumor Suppressor Proteins/*biosynthesis ; }, abstract = {BACKGROUND & OBJECTIVE: Fragile histidine triad(FHIT), a tumor suppressor candidate gene, encompasses FRA3B, a common region with the highest fragility in the human genome, and is altered in a large number of human cancers, particularly those of epithelial cell origin and associated with known carcinogenic agents. The aim of this study was to investigate the expression of FHIT protein, Fhit and the possible relationship between Fhit expression and clinicopathological indices in breast cancer.

METHODS: Fhit protein expression in 66 cases of formalin-fixed, paraffin-embedded breast cancer composed of 6 in situ and 60 invasive ductal carcinoma were detected with citrate-microwave-Streptavidin-HRP(SP) immunohistochemical method, using rabbit antibody to human FHIT gene protein and relationships to invasion and lymphatic metastasis were analyzed.

RESULTS: Thirty-eight (57.6%) cases of carcinomas showed a marked loss or absence of Fhit expression compared with the adjacent non-cancerous breast tissues, in which 22 cases were negative. The remain 18 (27.3%) showed stronger than, and 10 (15.2%) equal to the Fhit expression of the adjacent non-cancerous tissue. The lower expression of Fhit was found in 20/24(83.3%) cases with local or axillary lymphatic metastasis, and in 18/36 (50%) cases without metastasis in the invasive ductal carcinoma. Fhit expression was determined in all 6 cases of in situ ductal carcinoma did not show lower than non-cancerous tissue. There was a significant difference in the expression of Fhit between the breast cancers with and without lymphatic metastasis, both in ductal carcinoma (P < 0.01) and in invasive ductal carcinoma(P < 0.01).

CONCLUSIONS: The expression of Fhit is associated with invasion and metastasis of tumor in breast cancer. It is suggested that decreased Fhit expression may play an important role in the development and progression of the tumor, and thus may become a new prognostic marker for breast cancer.}, } @article {pmid12452061, year = {2002}, author = {He, JH and Liang, XM and Hou, JH and Huan, YL and Wu, QL and Xiao, YB}, title = {[Study of CD44v6 protein expression in intraductal papilloma and its malignant transformation of breast].}, journal = {Ai zheng = Aizheng = Chinese journal of cancer}, volume = {21}, number = {6}, pages = {615-618}, pmid = {12452061}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Glycoproteins/*biosynthesis ; Humans ; Hyaluronan Receptors/*biosynthesis ; Papilloma, Intraductal/*metabolism/pathology ; }, abstract = {BACKGROUND & OBJECTIVE: CD44v6 plays an important role in the malignant transformation of breast epithelia and is differentially expressed in normal and neoplastic breast tissue. The diagnostic value of this marker in differentiating malignant from benign breast lesions has not been well examined. This study was designed to evaluate the diagnostic value of CD44v6 protein in distinguishing between benign and malignant papillary lesions of the breast, which is be difficult morphologically, by determining the level of CD44v6 expression in different lesions of the breast.

METHODS: The level of CD44v6 protein was detected by immunohistochemistry in 111 paraffin-embeded blocks.

RESULT: The positive expressive rates of CD44v6 protein in the basal epithelial cells of the normal tissue, intraductal papilloma, and its malignant transformation, intraductal carcinoma, invasive ductal carcinoma were 95.00%, 85.72%, 66.66%, 66.66%, and 0.00% respectively. The difference between the intraductal papilloma and its malignant transformation was not significant(P > 0.05). However, the positive expressive rates of CD44v6 protein in the luminal epithelial cells of the above lesions were 5.00%, 20.41%, 83.34%, 93.33%, and 100% respectively. There was difference between intraductal papilloma and its malignant transformation(P < 0.01).

CONCLUSION: CD44v6 detection by immunohistochemistry is useful in distinguishing intraductal papilloma from its malignant transformation of the breast.}, } @article {pmid12440829, year = {2002}, author = {Tamiolakis, D and Papadopoulos, N and Cheva, A and Lambropoulou, M and Kotini, A and Jivannakis, T and Simopoulos, C}, title = {Immunohistochemical expression of alpha-smooth muscle actin in infiltrating ductal carcinoma of the breast with productive fibrosis.}, journal = {European journal of gynaecological oncology}, volume = {23}, number = {5}, pages = {469-471}, pmid = {12440829}, issn = {0392-2936}, mesh = {Actins/*metabolism ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Fibrosis/pathology ; Humans ; Immunohistochemistry ; *Muscle, Smooth ; Neoplasm Staging ; Prognosis ; Sampling Studies ; Sensitivity and Specificity ; }, abstract = {Myoepithelial cells are normally located between the epithelial cells and the basal lamina of secretory elements of exocrine glands. Their role in the histogenesis of breast tumours has been studied extensively, and a definite differentiation towards myoepithelial cells has been demonstrated in adenoid cystic carcinoma, adenomyoepithelioma, low-grade adenosquamous (syringomatous) carcinoma, pure malignant myoepithelioma and poorly differentiated myoepithelial-rich breast carcinoma. All these tumours are of low malignancy, with the exception of malignant myoepithelioma and poorly differentiated myoepithelial-rich carcinoma. We examined the possibility that invasive ductal carcinoma of the breast might show differentiation towards both epithelial and myoepithelial cells because there is no reason to assume that one type of differentiation necessarily excludes the other. We performed the avidin-biotin immunohistochemical analysis of 20 cases of infiltrating ductal carcinomas (IDCs) with diffuse fibrosis, 20 cases of IDCs without fibrosis and five cases of metaplastic carcinomas, to detect myoepithelial differentiation of the tumour cells. Myoepithelial differentiation was determined by the expression of alpha-smooth muscle actin (alpha-SMA). We concluded that IDCs with diffuse fibrosis are associated with a myoepithelial immunophenotype of carcinoma cells.}, } @article {pmid12437074, year = {2002}, author = {Hollender, P and Ittelett, D and Villard, F and Eymard, JC and Jeannesson, P and Bernard, J}, title = {Active matrix metalloprotease-9 in and migration pattern of dendritic cells matured in clinical grade culture conditions.}, journal = {Immunobiology}, volume = {206}, number = {4}, pages = {441-458}, doi = {10.1078/0171-2985-00193}, pmid = {12437074}, issn = {0171-2985}, mesh = {Cell Differentiation ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CCL20 ; Chemokines, CC/pharmacology ; Dendritic Cells/cytology/*enzymology/immunology/physiology ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/*metabolism ; Phenylalanine/*analogs & derivatives/pharmacology ; Protease Inhibitors/pharmacology ; Receptors, CCR6 ; *Receptors, Chemokine ; Thiophenes/pharmacology ; Tissue Inhibitor of Metalloproteinases/metabolism ; }, abstract = {Dendritic cells (DC) represent potent antigen presenting cells (APC) that are capable of generating tumor-specific immunity. In DC-based vaccination the migration of the infused DC from the site of injection to the secondary lymphoid organs might be critical to induce an effective immune response. Therefore we analyzed the migrating properties of maturing DC generated from human blood monocytes under culture conditions in compliance with the good manufacturing practice (GMP) guidelines. Highly purified CD14+ monocytes were differentiated into immature DC (iDC), then optimally matured as evidenced by CD83 expression. Time-lapse videomicroscopy and Transwell migration assays performed with or without Matrigel, proved mature DC (mDC) to be highly migrating cells compared to iDC although mDC migratory response varied markedly according to individuals (n= 15). Moreover, as shown by gelatin zymography and ELISA, mDC predominantly expressed both the active form of the matrix metalloprotease-9 (MMP-9) and low amounts of its physiological inhibitor, the tissue inhibitor of metalloprotease-1 (TIMP-1) which may explain their high migrating capacity through Matrigel layers. Macrophage inflammatory protein-3beta (MIP-3beta), strongly increased mDC migration through Matrigel by up-regulating the membrane MMP-9 active form suggesting that injected mDC could be selectively guided to T-cell areas of lymph nodes by this chemokine. Taken together, we demonstrate for the first time that mDC, but not iDC, prepared in clinical grade conditions are both physiologically invasive cells expressing chemokine-active and -sensitive MMP-9, which may be critical for their trafficking through tissues after injection. Consequently, we argue that migration characteristics should be included into a gold standard for DC administrated to patients.}, } @article {pmid12429029, year = {2002}, author = {Raccurt, M and Lobie, PE and Moudilou, E and Garcia-Caballero, T and Frappart, L and Morel, G and Mertani, HC}, title = {High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland.}, journal = {The Journal of endocrinology}, volume = {175}, number = {2}, pages = {307-318}, doi = {10.1677/joe.0.1750307}, pmid = {12429029}, issn = {0022-0795}, mesh = {Breast/pathology/physiopathology ; Carcinoma in Situ/*genetics/pathology ; Epithelium/pathology/physiology ; Female ; Fibroadenoma/*genetics ; Gene Expression/*genetics ; Growth Hormone/*genetics ; Humans ; Lymphatic Metastasis/genetics ; Mammary Neoplasms, Animal/*genetics ; Neoplasm Invasiveness/genetics ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {We have demonstrated and localized human GH (hGH) gene expression in surgical specimens of normal human mammary gland and in proliferative disorders of the mammary gland of increasing severity using sensitive in situ RT-PCR methodology. hGH mRNA identical to pituitary hGH mRNA was first detected by RT-PCR of RNA derived from samples of normal human mammary gland. Cellular localization of hGH gene expression in the normal mammary gland exhibited restriction to luminal epithelial and myoepithelial cells of the ducts and to scattered stromal fibroblasts. We subsequently examined the expression of the hgh gene in three progressive proliferative disorders of the human mammary gland, i.e. A benign lesion (fibroadenoma), a pre-invasive stage (intraductal carcinoma) and an invasive ductal carcinoma. hGH mRNA was readily detected in the tumoral and non-tumoral epithelial components and also in cells of the reactive stroma including fibroblasts, myofibroblastic and myoepithelial cells, inflammatory infiltrate lymphocytes and endothelial cells in areas of neovascularization. In all three proliferative disorders examined, the intensity of the cellular labeling observed in both the epithelial and stromal compartments was always stronger compared with that in adjacent normal tissue. hGH protein was also present in significantly higher concentration in extracts derived from proliferative disorders of the mammary gland compared with extracts derived from normal mammary gland. We also examined hGH gene expression in axillary lymph nodes not containing and containing metastatic mammary carcinoma. hGH gene expression was evidenced in metastatic mammary carcinoma cells and in reactive stromal cells by both in situ hybridization and in situ RT-PCR. In contrast, in lymph nodes not containing metastatic mammary carcinoma, hGH mRNA was detected only by use of in situ RT-PCR. Thus, increased expression of the hGH gene in the epithelial component and the de novo stromal expression in proliferative disorders of the mammary gland are suggestive of a pivotal role for autocrine hGH in neoplastic progression of the mammary gland.}, } @article {pmid12423812, year = {2002}, author = {Frei, KA and Bonel, HM and Forrer, P and Alleman, J and Steiner, RA}, title = {Primary breast lymphoma, contralateral breast cancer, and bilateral Brenner tumors of the ovary.}, journal = {Obstetrics and gynecology}, volume = {100}, number = {5 Pt 2}, pages = {1079-1082}, doi = {10.1016/s0029-7844(02)02070-7}, pmid = {12423812}, issn = {0029-7844}, mesh = {*Breast Neoplasms/diagnosis/therapy ; *Brenner Tumor/diagnosis/therapy ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Combined Modality Therapy ; Female ; Humans ; *Lymphoma, B-Cell/diagnosis/therapy ; Magnetic Resonance Imaging ; Mammography ; Middle Aged ; *Neoplasms, Multiple Primary/diagnosis/therapy ; *Ovarian Neoplasms/diagnosis/therapy ; }, abstract = {BACKGROUND: Primary lymphoma of the breast is an unusual clinical entity. Its presence with invasive breast cancer and bilateral Brenner tumors of the ovary is very rare.

CASE: We report a 62-year-old woman referred for further evaluation of a palpable mass in her breast. She was diagnosed and treated for simultaneous primary lymphoma of the right breast, contralateral invasive ductal carcinoma, and bilateral Brenner tumors of the ovary. One year after treatment, she is free of recurrence or progression.

CONCLUSION: Compared with breast carcinoma, primary breast lymphoma is a rare disease but should be considered in the differential diagnosis of breast masses. The presence of both breast malignancies presents a challenge in treatment decisions.}, } @article {pmid12417044, year = {2002}, author = {Kawahira, H and Hasebe, T and Kinoshita, T and Sasaki, S and Konishi, M and Nakagori, T and Inoue, K and Oda, T and Takahashi, S and Ochiai, T and Ochiai, A}, title = {The intraductal carcinoma component is a significant prognostic parameter in patients with invasive ductal carcinoma of the pancreas.}, journal = {Japanese journal of cancer research : Gann}, volume = {93}, number = {10}, pages = {1138-1144}, pmid = {12417044}, issn = {0910-5050}, mesh = {Adult ; Aged ; Carcinoma, Ductal, Breast/mortality/*pathology ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms/mortality/*pathology ; Prognosis ; }, abstract = {We have sometimes encountered invasive ductal carcinomas (IDCs) of the pancreas containing intraductal carcinoma components in the intra- and / or extra-tumor area. The purpose of this study was to investigate whether intraductal carcinoma components would be useful for predicting the outcome of IDC patients. Forty-seven surgically treated IDCs were examined, and all histological tumor sections were stained with Elastica to accurately confirm intraductal carcinoma components. Well-known clinicopathological parameters that exhibited a significant correlation in the univariate analyses for predicting disease-free survival (DFS) and overall survival (OS) were entered into the Cox proportional hazard multivariate analysis. Since the lowest P-value predicting DFS or OS periods was observed in IDCs with more than 10% intraductal carcinoma components and those with 10% or less intraductal carcinoma components (P = 0.028 and P = 0.019), we established the cutoff value of intraductal carcinoma components at 10%. In the multivariate analyses for DFS and OS, the presence of more than 10% intraductal carcinoma components showed a marginally significant increase in the hazard rate (HR) of tumor recurrence (P = 0.067) and significantly increased the HR of mortality (P = 0.040). The present study demonstrated that IDCs with more than 10% intraductal carcinoma components were associated with a significantly better patient outcome than those with 10% or less intraductal carcinoma components.}, } @article {pmid12412200, year = {2002}, author = {Wang, ZY and Morinobu, A and Kawano, S and Saegusa, J and Wang, B and Kumagai, S}, title = {Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes.}, journal = {Clinical and experimental rheumatology}, volume = {20}, number = {5}, pages = {683-688}, pmid = {12412200}, issn = {0392-856X}, mesh = {Antirheumatic Agents/*pharmacology ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Dendritic Cells/cytology/*drug effects/immunology ; Flow Cytometry ; Gold Sodium Thiomalate/*pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology ; Humans ; Interleukin-12/*immunology ; T-Lymphocytes/drug effects/*immunology ; }, abstract = {OBJECTIVE: Gold sodium thiomalate (GST) is a drug commonly used for the treatment of rheumatoid arthritis (RA). To clarify the mechanism of therapeutic effects of GST on RA, we investigated if GST affects the differentiation of dendritic cells (DC), which are thought to play a pivotal role in RA pathogenesis.

METHODS: We generated immature DC (iDC) in vitro from PB monocytes during the 5 to 7-day culture in the presence of IL-4 and GM-CSF. Mature DC (mDC) were induced by adding TNF alpha on day 5 of the 7-day culture with GM-CSF and IL-4. DC capacity of stimulating T cells was examined in allogenic MLR using generated DC as stimulators. IL-12 production from DC was assayed with ELISA.

RESULTS: We found that: 1) mDC generated in the presence of GST showed lower expression of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR compared to control mDC on FACS analysis. 2) GST-treated mDC showed reduced capacity of stimulating allogenic T cells in mixed leukocyte reaction. 3) IL-12p70 production after stimulation with SAC or LPS plus IFN gamma was markedly reduced in GST-treated mDC.

CONCLUSION: GST suppresses the differentiation and function of DC generated from peripheral blood monocytes. This previously unknown action may explain the in vivo effects of GST in the treatment of RA.}, } @article {pmid12404521, year = {2002}, author = {Cheung, YC and Lee, KF and Ng, SH and Chan, SC and Wong, AM}, title = {Sonographic features with histologic correlation in two cases of palpable breast cancer after breast augmentation by liquid silicone injection.}, journal = {Journal of clinical ultrasound : JCU}, volume = {30}, number = {9}, pages = {548-551}, doi = {10.1002/jcu.10110}, pmid = {12404521}, issn = {0091-2751}, mesh = {Biopsy, Needle ; Breast Implants/*adverse effects ; Breast Neoplasms/*diagnostic imaging/*etiology ; Carcinoma, Ductal, Breast/diagnostic imaging/etiology ; Carcinosarcoma/diagnostic imaging/etiology ; Female ; Humans ; Middle Aged ; Silicone Gels/*adverse effects ; Time Factors ; Ultrasonography, Mammary ; }, abstract = {Sonography is rarely used to evaluate the breasts in patients who have undergone liquid silicone injections for breast augmentation because strong acoustic shadowing from the resulting silicone granulomas hampers the examination. We report on 2 patients who underwent silicone injection 18 and 20 years earlier and in whom breast cancers (1 invasive ductal carcinoma and 1 carcinosarcoma) were diagnosed by sonographically guided core-needle biopsy. On sonograms, both cancers had a peripheral hypoechoic rim surrounding an echogenic center. The echogenic center corresponded histologically to a silicone granuloma in 1 patient and to a large area of necrosis in the other; the hypoechoic rims corresponded to areas of cancer in both patients.}, } @article {pmid12400981, year = {2002}, author = {Zheng, WQ and Looi, LM and Cheah, PL}, title = {Correlation between laminin and cathepsin D expressions in breast carcinoma.}, journal = {Tumori}, volume = {88}, number = {4}, pages = {296-299}, doi = {10.1177/030089160208800411}, pmid = {12400981}, issn = {0300-8916}, mesh = {Breast Neoplasms/*chemistry ; Cathepsin D/*analysis ; Female ; Humans ; Immunohistochemistry ; Laminin/*analysis ; }, abstract = {AIMS AND BACKGROUND: Laminin is a major glycoprotein component of basement membrane which is an important barrier to tumor cells which must be breached before metastatic spread can occur. Proteolytic enzymes play an important role in mediating the passage of cancer cells through the basement membrane (BM) and extracellular matrix. We have compared the patterns of laminin and cathepsin D (CD) expressions in a range of benign and malignant breast lesions to better understand the process of tumor progression.

METHODS: One hundred and sixty-two cases of breast samples comprising 18 fibroadenomas, 22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26 carcinomas with intraductal components were evaluated for laminin and cathepsin D expressions by immunohistochemical staining.

RESULTS: The prevalence of CD positivity in both neoplastic and stromal cell components were significantly higher in higher histological grade tumors compared to lower grades (P <0.01). Various severity of BM disruption correlated with histological grade of the carcinomas (P <0.001). There was a negative correlation between the laminin expression and CD presence.

CONCLUSIONS: It was confirmed that in a process of cancer cell invasion and metastasis, it could be necessary with the basement membrane disruption by proteinase secreted by cancer cells and especially by stroma cells of cancer.}, } @article {pmid12390417, year = {2002}, author = {Mannweiler, S and Tsybrovskyy, O and Regauer, S}, title = {The flow cytometric DNA index can predict the presence of lymph node metastases in invasive ductal breast carcinoma.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {110}, number = {7-8}, pages = {580-586}, doi = {10.1034/j.1600-0463.2002.1007810.x}, pmid = {12390417}, issn = {0903-4641}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; DNA, Neoplasm/*metabolism ; Female ; Flow Cytometry ; Humans ; Lymph Nodes/metabolism/*pathology ; Lymphatic Metastasis ; Middle Aged ; Predictive Value of Tests ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Sensitivity and Specificity ; }, abstract = {Axillary lymph node (LN) dissection is an important staging procedure for invasive ductal breast carcinoma (IDC), but causes elevated morbidity. Reliable preoperative prediction of metastases is at present not possible. We investigated whether flow cytometric analysis of primary IDC can correctly predict the presence of LN metastases at the time of primary diagnosis. In 341 primary IDC, DNA index (DI) in absolute values, S-phase fraction (SPF), size of the primary tumor, tumor grade (G), estrogen/progesterone receptors (ER/PR) expression and age were analysed and correlated with the axillary LN status with the aim of correctly predicting the LN status. No predictive value was identified for S-phase fraction (SPF), tumor grade, or ER/PR expression. The DI correlated statistically with LN status in all patients. A practically useful association was, however, only observed in 37 women aged 45-58 years with an IDC >2 cm diameter: a DI >1.44 predicted the presence of LN metastases at the time of operation with a specificity of 100% and a sensitivity of 89%, a negative predictive value of 91% and a positive predictive value of 100%. Determination of the absolute values of the DI may be a useful adjunct to sentinel LN preparation when predicting the axillary LN status and may spare some women the morbidity associated with axillary LN dissection.}, } @article {pmid12388496, year = {2002}, author = {Rosen, EL and Bentley, RC and Baker, JA and Soo, MS}, title = {Imaging-guided core needle biopsy of papillary lesions of the breast.}, journal = {AJR. American journal of roentgenology}, volume = {179}, number = {5}, pages = {1185-1192}, doi = {10.2214/ajr.179.5.1791185}, pmid = {12388496}, issn = {0361-803X}, mesh = {*Biopsy, Needle ; Breast Neoplasms/epidemiology/*pathology/surgery ; Carcinoma in Situ/epidemiology/pathology/surgery ; Carcinoma, Ductal, Breast/epidemiology/pathology/surgery ; Carcinoma, Papillary/epidemiology/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Incidence ; Mammography ; Predictive Value of Tests ; Retrospective Studies ; Ultrasonography, Mammary ; }, abstract = {OBJECTIVE: Our objective was to assess the incidence of papillary lesions of the breast diagnosed at imaging-guided core needle biopsy and the need for surgical excision after a benign diagnosis.

MATERIALS AND METHODS: This retrospective study included 1374 patients with consecutive suspicious breast lesions that underwent either mammography or sonographically guided large-core needle breast biopsy. Fifty-seven lesions (4%) were classified as papillary lesions. Eleven of the 57 cases were lost to follow-up (n = 6) or had not yet shown 2 years of stability (n = 5) and were excluded from this study. The remaining 46 papillary lesions constitute our study population.

RESULTS: Surgical excision was performed in 17 (37%) of 46 papillary lesions. In the group of patients whose lesions were recommended for excision because carcinoma was identified at core biopsy, surgical excision revealed one false-positive and two true-positive diagnoses. In four cases, histologic diagnoses of the excisional biopsy and the core needle biopsy were discordant. One false-positive finding at core needle biopsy initially was interpreted as invasive ductal carcinoma on the basis of core needle biopsy specimens. In three false-negative findings, the initial diagnosis at core needle biopsy was upgraded after surgical excision. Two cases of papilloma with adjacent atypical ductal hyperplasia and one of atypical papilloma were upgraded to ductal carcinoma in situ after surgical excision. Imaging follow-up was performed in the remaining 29 patients. All lesions were stable or had decreased in size during the 2-year follow-up period. The negative predictive value of core needle biopsy for excluding malignancy among the papillary lesions diagnosed in our study was 93%.

CONCLUSION: When the histologic diagnosis is benign, our data suggest that papillary lesions may be safely managed with imaging follow-up rather than with surgical excision. However, atypical papillary lesions or those associated with atypia require surgical excision because histologic underestimation occurs at a frequency similar to that in other atypical lesions undergoing core needle biopsy.}, } @article {pmid12380765, year = {2002}, author = {Leder, U and Pohl, HP and Baier, V and Baumert, M and Liehr, M and Haueisen, J and Voss, A and Figulla, HR}, title = {Alternans of blood pressure and heart rate in dilated cardiomyopathy.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {25}, number = {9}, pages = {1307-1314}, doi = {10.1046/j.1460-9592.2002.01307.x}, pmid = {12380765}, issn = {0147-8389}, mesh = {Blood Pressure/*physiology ; Cardiomyopathy, Dilated/*physiopathology ; Electrocardiography ; Heart Rate/*physiology ; Humans ; Middle Aged ; Pilot Projects ; *Pulse ; }, abstract = {Impaired myocardial performance is known to be associated with electrical and mechanical beat-to-beat alternans phenomena. The alternans in blood pressure and heart rate and their interdependency in idiopathic dilated cardiomyopathy (IDC) were studied. The arterial blood pressure and the electrocardiograph (ECG) were continuously recorded in 22 patients suffering from IDC (age 49 +/- 13 years, ejection fraction 0.33 +/- 0.13, left ventricular diameter of 67 +/- 8 mm) and in 21 healthy controls (age 52 +/- 15 years). The beat-to-beat variations of the interbeat intervals (IBI) and of the blood pressure amplitudes (AMP) were measured. An alternans beat was defined as a beat preceded and followed by beats that had higher or lower values in the respective modality. The percentages of singular and repetitive alternans patterns, and the interdependency of the alternans patterns in AMP and IBI were assessed. The study found significantly more singular and repetitive alternans patterns in the IDC group compared to the control group both in the analysis of AMP and IBI (singular alternans in IBI: 55 +/- 11 vs 47 +/- 7%, P < 0.01; singular alternans in AMP: 61 +/- 15 vs 45 +/- 6%, P < 0.01; triple alternans in IBI: 29 +/- 18 vs 16 +/- 9%, P < 0.01; triple alternans in AMP: 34 +/- 24 vs 12 +/- 7%, P < 0.01). The amplitudes of the AMP alternans patterns were higher in IDC compared to controls (9 +/- 7 vs 4 +/- 2% of AMP, P = 0.01) whereas they did not differ in IBI. The correlation analysis revealed a significant interdependency of the alternans pattern in IBI and AMP in 18 of 22 IDC patients and in 12 of 21 controls (r = 0.50 +/- 0.21 [IDC]; r = 0.26 +/- 0.05 [controls]). The slope of the linear regression (delta AMP vs delta IBI) was steeper in the IDC group compared to the control group (62 +/- 50 vs 20 +/- 22 mmHg/s, P < 0.01). The percentages of alternans patterns appearing in IBI and AMP were positively correlated to the left ventricular diameter (r = 0.70 in the IBI, and r = 0.30 in the AMP). The blood pressure amplitude and the heart rate did not differ between the two groups. Patients suffering from IDC have a higher prevalence, stability, amplitude, and interdependency of alternans patterns in IBI and AMP compared to the control group. The amount of alternans patterns indicates the stage of disease. The alternans analysis may have impact on the functional assessment of patients suffering from heart failure.}, } @article {pmid12378597, year = {2002}, author = {Lu, D and Masood, S and Khalbuss, WE and Bui, M}, title = {A subset of breast invasive ductal carcinoma with distinctive cytomorphology, aggressive clinical behavior, and unique immunologic profiles.}, journal = {Cancer}, volume = {96}, number = {5}, pages = {294-300}, doi = {10.1002/cncr.10745}, pmid = {12378597}, issn = {0008-543X}, mesh = {Adult ; Age Distribution ; Aged ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis ; }, abstract = {BACKGROUND: Invasive ductal carcinoma of the breast is a heterogeneous collection of divergent types of carcinomas. Some subtypes have been characterized by histologic observations. This study describes a distinctive subset recognized through cytomorphologic examination of breast carcinoma specimens obtained by fine-needle aspiration biopsies (FNAB). Identification of this subset is established further by analyses of its clinical and immunologic characteristics.

METHODS: One hundred patients underwent FNAB and were diagnosed with breast ductal carcinoma. These diagnoses were followed by surgical resections and histologic evaluation of tumors. Immunohistochemical analyses of estrogen receptor, progesterone receptor, Her2/neu, p53 protein, and Ki-67 were performed. Patient's age, race, and family history of breast carcinoma were obtained. The objective of the study is to identify a cytomorphologically distinctive, clinically relevant, subset of breast carcinomas.

RESULTS: A subset carcinoma was recognized by cytomorphologic examination of Pap-stained FNAB slides. This subset consisted of seven patients with a median age of 37 years. At the time of surgical resection, all patients had axillary lymph node metastases. Six of seven patients had distant metastases. Immunohistochemical studies revealed that all tumors are positive for p53 protein and negative for estrogen and progesterone receptors.

CONCLUSION: This study presented a unique subset of breast ductal carcinomas that involved young patients and had aggressive growth behavior. These tumors expressed p53 protein but not estrogen and progesterone receptors.}, } @article {pmid12355004, year = {2002}, author = {Yeung, DK and Yang, WT and Tse, GM}, title = {Breast cancer: in vivo proton MR spectroscopy in the characterization of histopathologic subtypes and preliminary observations in axillary node metastases.}, journal = {Radiology}, volume = {225}, number = {1}, pages = {190-197}, doi = {10.1148/radiol.2243011519}, pmid = {12355004}, issn = {0033-8419}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Biopsy, Needle ; Breast Neoplasms/chemistry/*diagnosis/pathology ; Carcinoma, Ductal, Breast/chemistry/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*diagnosis/pathology ; Choline/analysis ; Contrast Media ; Female ; Humans ; Lymph Nodes/chemistry ; Lymphatic Metastasis ; *Magnetic Resonance Spectroscopy ; Middle Aged ; Sensitivity and Specificity ; }, abstract = {PURPOSE: To assess the relationship between breast cancer subtypes and choline detection by using in vivo proton magnetic resonance (MR) spectroscopy and to assess the feasibility of proton MR spectroscopy in the study of axillary lymph node metastases.

MATERIALS AND METHODS: Breast and lymph node MR spectroscopy of lesions identified at contrast material-enhanced MR imaging was performed in 39 patients with breast cancer. Spectroscopic and histopathologic findings were determined and compared. The sensitivity, specificity, and accuracy of the MR spectroscopic technique in the detection of axillary lymph node metastases were determined.

RESULTS: There were four cases of ductal carcinoma in situ (DCIS) and 34 invasive carcinomas, including three with an extensive in situ component. Twenty-six breast lesions were positive for choline at MR spectroscopy; nine, negative; and three, failed cases (ie, determination of positive or negative for choline could not be made). No data were available for one lesion. Four of the nine negative findings were DCIS; three, infiltrating ductal carcinoma (IDC) with an extensive in situ component; and two, IDC. Fourteen axillary lymph nodes were positive for choline; 17, negative; and four, failed cases. No data were available for four nodes. Comparison of the preliminary diagnostic indexes of the MR spectroscopic technique with the ultrasonographically guided fine-needle aspiration biopsy findings in lymph nodes revealed a sensitivity of 82%, specificity of 100%, and accuracy of 90%.

CONCLUSION: Choline is consistently detected in IDC. DCIS and IDC with an extensive in situ component are likely to be negative for choline at MR spectroscopy. In vivo proton MR spectroscopy of axillary lymph nodes in patients with breast cancer is feasible and has encouraging preliminary results.}, } @article {pmid12354345, year = {2002}, author = {Madjar, S and Appell, RA}, title = {Impaired detrusor contractility: anything new?.}, journal = {Current urology reports}, volume = {3}, number = {5}, pages = {373-377}, pmid = {12354345}, issn = {1527-2737}, mesh = {Humans ; *Muscle Contraction ; Muscle, Smooth/physiopathology ; Nervous System/physiopathology ; Urinary Bladder Diseases/*physiopathology/therapy ; }, abstract = {Impaired detrusor contractility (IDC) is a poorly defined entity that represents a treatment challenge for the urologist. The etiology of IDC is variable and may include neurologic disorders, inflammatory conditions, and pharmacologic and psychogenic causes. The gold standard for the treatment of IDC is clean intermittent catheterization (CIC). Although well-established as efficacious and safe, CIC may be conceived as a major burden on a patient's quality of life and has been associated with urinary tract infections and urethral and/or bladder injury. Alternative treatment modalities for IDC can be divided into interventions at the nervous system supplying the bladder, the bladder itself, or the bladder outlet. We review and discuss novel and creative treatment options for patients with IDC that have been developed or tested over the past decade.}, } @article {pmid12353810, year = {2002}, author = {Tran, DD and Lawson, JS}, title = {Microcysts and breast cancer: a study of biological markers in archival biopsy material.}, journal = {Breast cancer research and treatment}, volume = {75}, number = {3}, pages = {213-220}, doi = {10.1023/a:1019969730552}, pmid = {12353810}, issn = {0167-6806}, mesh = {Biomarkers, Tumor/*metabolism ; Biopsy ; Breast/metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cyclin D1/metabolism ; Estrogen Receptor alpha ; Female ; Fibrocystic Breast Disease/*metabolism/pathology ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Breast cysts are associated with an increased risk of breast cancer. Some biomarkers such as estrogen receptor alpha (ERa), progesterone receptor (PR), and cyclin D1, show similar patterns of expression in epithelial cells lining breast cysts as malignant epithelial cells in local and invasive ductal breast cancer. We have attempted to answer two questions: (1) Do epithelial cells lining breast microcysts (cysts which can only be seen with a microscope) express biomarkers in a similar pattern to breast ductal carcinoma in situ and invasive ductal carcinoma? (2) Are breast microcysts precursors of breast cancer or are they part of normal involution of the breast? Seventy two archival open breast biopsy specimens of ductal carcinoma in situ and invasive ductal carcinoma and 32 normal breast biopsies from Australian women who had breast reduction surgery were selected from hospital archives. All specimens were analysed by standard immunohistochemistry for ERa, PR, cyclin D1, bcl-2, p53 and erbB-2 expression. In the same specimens, the pattern of high biomarker expression was very similar for all the above biomarkers in epithelial cells lining microcysts and in both ductal carcinoma in situ and invasive ductal carcinoma c. ErbB-2 was not expressed in normal control specimens. ErbB-2 was expressed in the same specimens in an increasing proportion of normal breast acini, microcysts and cancer cells in 36% of specimens with breast cancer. An apparent progression was observed from normal breast acini, to proliferation of epithelial cells in microcysts, ductal carcinoma in situ and invasive ductal carcinoma in the same specimen. When these findings are considered with other reports we conclude: (1) that epithelial cells lining breast cysts highly express biomarkers in a similar pattern to ductal carcinoma in situ and invasive ductal carcinoma; (2) that some microcysts are not part of normal involution of the breast and in some women may be part of the transition from normal to cancer.}, } @article {pmid12353144, year = {2002}, author = {Yonezawa, S and Nakamura, A and Horinouchi, M and Sato, E}, title = {The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms.}, journal = {Journal of hepato-biliary-pancreatic surgery}, volume = {9}, number = {3}, pages = {328-341}, doi = {10.1007/s005340200037}, pmid = {12353144}, issn = {0944-1166}, mesh = {Carcinoma, Pancreatic Ductal/*metabolism/pathology ; Glycosylation ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Mucin 5AC ; Mucin-1/*metabolism ; Mucin-2 ; Mucins/*metabolism ; Neoplastic Processes ; Pancreas/metabolism ; Pancreatic Neoplasms/*metabolism/pathology ; Prognosis ; }, abstract = {BACKGROUND/PURPOSE: Mucins are high molecular weight glycoproteins that have oligosaccharides attached to the apomucin protein backbone by O-glycosidic linkages. Here, we report the expression of MUC1 mucin (membrane-bound mucin), MUC2 mucin (intestinal-type secretory mucin), and MUC5AC mucin (gastric-type secretory mucin) in invasive ductal carcinomas (IDCs; n = 46) and intraductal papillary-mucinous neoplasms (IPMNs; n = 33) of the pancreas, and the relationship of this expression with malignant potential.

METHODS: To clarify the precise expression pattern of mucins in IPMNs, we classified IPMNs into three histologic subtypes; IPMN-dark cell type (n = 19), IPMN-clear cell type (n = 10), and IPMN-compact cell type (n = 4).

RESULTS: IDC, with a poor outcome, showed a pattern of MUC1(+), MUC2(-), and MUC5AC(+ or -). In contrast, IPMN-dark cell type tumors, with a fairly favorable outcome, showed a pattern of MUC1(-), MUC2(+), and MUC5AC (+), and IPMN-clear cell type tumors, with a favorable outcome, showed a pattern of MUC1(-), MUC2(-), and MUC5AC(+). On the other hand, IPMN-compact cell type tumors showed a pattern of MUC1(+), MUC2 (-), and MUC5AC(+). In IPMN-dark cell type tumors with carcinomatous change showing invasive growth, the invasive areas acquired a characteristic of MUC1 expression that was usually seen in IDC, although their main noninvasive lesions showed no MUC1 expression. The IPMN-compact cell type tumors usually showed high cellular atypia and frequent MUC1 expression, even in the noninvasive areas.

CONCLUSIONS: Our study of the mucin expression pattern in IDC and IPMN shows that this pattern may be related to the biological behavior of pancreatic tumors and their malignant potential.}, } @article {pmid12322635, year = {1998}, author = {Tolentino, RS and Ang, SD and Cajacom, CC and Eufemio, GG and Talla, V and Lo, RW}, title = {The prognostic significance of the S-phase fraction and DNCA ploidy in node-negative estrogen receptor-positive breast cancer.}, journal = {Philippine journal of surgical specialties}, volume = {53}, number = {1}, pages = {25-30}, pmid = {12322635}, issn = {0031-7691}, mesh = {Asia ; Asia, Southeastern ; *Breast Neoplasms ; Developing Countries ; *Diagnosis ; Disease ; *Longitudinal Studies ; Neoplasms ; Philippines ; *Research ; *Therapeutics ; }, abstract = {The aim of this study was to determine the significance of the phase fraction S-phase fraction (SPF) and DNA ploidy as determined by DNA flow cytometry on the prognosis of patients with Stage 1 (TINOMO) and stage II A (T2NOMO) breast cancer who had estrogen receptor-positive tumors. A total of 45 patients with invasive ductal carcinoma were studied. The median follow-up was 3.8 years. The prognostic cut-off for the SPF of the 45 patients was 34% as determined by log rank test and this was used to classify patients into low (34%) and high (34%) SPF groups. 30 patients (67%) had low SPF. 36 (80%) of the tumors examined were diploid. Using the cut-off, the SPF had no prognostic value in Stage 1 breast cancer patients. There was significantly longer disease-free survival and overall survival in Stage II A patients with low SPF compared to Stage II A patients with high SPF (96% vs. 50% at 4 years, p = 0.02, and 100% vs. 62% at 4 years, p = 0.03, respectively). No significant prognostic value was noted with the DNA ploidy status in both groups of patients.}, } @article {pmid12297479, year = {2002}, author = {Ji, YQ and Sun, PW and Hu, JX}, title = {Diagnosis and surgical treatment of congenital dextrocardia.}, journal = {Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA}, volume = {22}, number = {6}, pages = {536-538}, pmid = {12297479}, issn = {1000-2588}, mesh = {Adolescent ; Child ; Child, Preschool ; Dextrocardia/diagnosis/*surgery ; Female ; Humans ; Infant ; Male ; Treatment Outcome ; }, abstract = {OBJECTIVE: To understand the pathological features of congenital dextrocardia and explore its diagnosis and surgical treatment.

METHOD: The clinical data from 32 cases of congenital dextrocardia were collected to understand the major cardiac anomalies and evaluate the diagnostic approaches of this disease. Analysis of the effect of surgical treatment was also conducted in 16 among the 32 cases.

RESULTS: Complex anomalies such as transposition of great artery (TGA), single ventricle (SV), common trunk (CMT) formation for the arteries were found in 8 out of 13 mirror-image dextrocardia cases, most of the dextroversion (DV) accompanied by physiological correction of the TGA (C-TGA, 11/17) which often involved ventricle septal defect (VSD) and pulmonary stenosis (PS, 8/11). Another 2 cases diagnosed as isolated dextrocardia (IDC) also suffered TGA combined with complete atrioventricular canal (CAVC) defect. Definite diagnoses of dextrocardia (DC) were derived from X-ray examination, including thoracic-abdominal plain X-ray film, hilar computed tomography, high kV chest plain film or ultrafast CT, echocardiogram and angiography. Fontan operation was performed in 8 cases and anatomical correction in 7 with surgical exploration in 1 case. Thirteen patients survived, among whom 8 had complex cardiac defect and 5 of them received modified Fontan operation or total cavopulmonary connection (TCPC).

CONCLUSIONS: Complex cardiac anomalies are not rare in mirror-image dextrocardia, and dextroversion and isolated dextrocardia were usually related to C-TGA+VSD+PS and TGA+CAVC respectively. X-ray examinations are of great significance in the diagnoses and classification of dextrocardia, and echocardiogram and ultrafast CT constitute the major modalities for clarifying intracardial defect and surgical indications. Fontan operations, including modified Fontan and total cavopulmonary connection, might be hopeful surgical treatment for complex congenital heart disease when indications are carefully evaluated.}, } @article {pmid12271427, year = {2002}, author = {Neglia, D and Sambuceti, G and Iozzo, P and L'Abbate, A and Strauss, HW}, title = {Myocardial metabolic and receptor imaging in idiopathic dilated cardiomyopathy.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {29}, number = {10}, pages = {1403-1413}, doi = {10.1007/s00259-002-0898-y}, pmid = {12271427}, issn = {1619-7070}, mesh = {Cardiomyopathy, Dilated/complications/*diagnostic imaging/*metabolism ; Cerebrovascular Circulation ; Energy Metabolism ; Fatty Acids/metabolism ; Fluorodeoxyglucose F18/pharmacokinetics ; Glucose/metabolism ; Heart/*diagnostic imaging/innervation ; Humans ; Myocardial Ischemia/complications/diagnostic imaging/metabolism ; Myocardium/*metabolism ; Parasympathetic Nervous System/diagnostic imaging/metabolism ; Radionuclide Imaging ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Adrenergic/metabolism ; Receptors, Adrenergic, beta/metabolism ; Receptors, Cell Surface/*metabolism ; Receptors, Muscarinic/metabolism ; Sympathetic Nervous System/diagnostic imaging/metabolism ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a distinct disease of the myocardium, of unknown etiology. The disease can occur acutely, or evolve in a subacute fashion. IDC is often associated with a substantial impairment of ventricular function, which may recover over time. Although spontaneous recovery of LV function occurs in 20%-45% of newly diagnosed patients, the majority of patients do not do well. IDC has an average 5-year mortality of 20%. Abnormalities of energetics, perfusion, and adrenergic control of the myocardium are markers of the status of LV dysfunction. As the heart fails, changes occur in the production and catabolism of high-energy substrates, the efficiency of mitochondrial oxidative processes, the distribution of resting perfusion and coronary vasodilating capacity and the adrenergic receptor density and function. This article reviews the information provided by metabolic and receptor imaging in patients with IDC, and the role the data may play in patient management.}, } @article {pmid12270725, year = {2002}, author = {Murabayashi, N and Kurita-Taniguchi, M and Ayata, M and Matsumoto, M and Ogura, H and Seya, T}, title = {Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification.}, journal = {Microbes and infection}, volume = {4}, number = {8}, pages = {785-794}, doi = {10.1016/s1286-4579(02)01598-8}, pmid = {12270725}, issn = {1286-4579}, mesh = {Animals ; Antigens, CD/metabolism ; *Cell Differentiation ; Chlorocebus aethiops ; Dendritic Cells/cytology/*immunology/metabolism/*virology ; *Drosophila Proteins ; Flow Cytometry ; Glycoproteins/genetics/*metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunoglobulins/genetics/*metabolism ; Ligands ; Measles virus/genetics/*growth & development/immunology ; Membrane Cofactor Protein ; Membrane Glycoproteins/*metabolism ; RNA, Messenger/genetics/metabolism ; Receptors, Cell Surface/*metabolism ; Signaling Lymphocytic Activation Molecule Family Member 1 ; Toll-Like Receptor 2 ; Toll-Like Receptors ; Vero Cells ; *Virus Replication ; }, abstract = {Human CD46 (membrane cofactor protein, or MCP) and CDw150 (signaling lymphocyte activation molecule, or SLAM) serve as receptors for measles virus (MV), which induces marked host immune suppression. Although monocytes express CD46, they are considerably resistant to MV. Once monocytes differentiate into immature myeloid dendritic cells (iDCs) (GM-CSF + IL-4-treated), the cells become susceptible to MV. Therefore, we have identified CD46-adapted and CDw150-adapted strains of MV, and the dynamics of CD46 and CDw150 during monocyte-iDC conversion were examined in conjunction with MV susceptibility. Strikingly, CDw150 was not detected in monocytes and moderately induced in iDCs, while CD46 was constantly expressed in monocyte-to-iDC differentiation. Thus, iDCs were found to become highly permissive to CDw150-adapted MV strains via expression of CDw150. In fact, polyclonal and monoclonal antibodies that specifically blocked the MV receptor function of CD46 or CDw150 cancelled MV replication in iDCs according to the preferential usage of either CD46 or CDw150 in each strain of MV. Next, we showed that DCs that matured via stimulation of their Toll-like receptors (TLRs) 2 and/or 4 exhibited an approximately fivefold increase in CDw150 at the protein level, and concomitantly, higher levels of MV amplification were observed in mixed culture of lymphocytes than in iDCs without TLR2/4 stimuli. Hence, amplification of CDw150-dependent MV strains was augmented in DCs parallel with the levels of CDw150 in the presence of lymphocytes possessing CDw150. TLR-mediated functional potential of DCs may affect the degree of MV amplification through distinct MV strain-specific receptor usage of CDw150 or CD46.}, } @article {pmid12223529, year = {2002}, author = {Yang, D and Chen, Q and Gertz, B and He, R and Phulsuksombati, M and Ye, RD and Oppenheim, JJ}, title = {Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation.}, journal = {Journal of leukocyte biology}, volume = {72}, number = {3}, pages = {598-607}, pmid = {12223529}, issn = {0741-5400}, mesh = {Amino Acid Sequence ; Antigen Presentation ; Calcium Signaling/drug effects ; Chemotaxis, Leukocyte/drug effects ; Dendritic Cells/cytology/drug effects/*metabolism ; Endocytosis/drug effects ; Gene Expression Regulation/drug effects ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Ligands ; Lipopolysaccharides/pharmacology ; Microscopy, Confocal ; Molecular Sequence Data ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Oligopeptides/pharmacology ; Peptide Fragments/immunology/pharmacology ; Peptides/pharmacology ; RNA, Messenger/biosynthesis/genetics ; Receptors, Formyl Peptide ; Receptors, Immunologic/*biosynthesis/genetics/physiology ; Receptors, Peptide/*biosynthesis/genetics/physiology ; Recombinant Fusion Proteins/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Virulence Factors, Bordetella/pharmacology ; }, abstract = {Immature and mature dendritic cells (iDC and mDC, respectively) migrate to different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary lymphoid organs, respectively, to fulfill their roles in the induction of primary, Ag-specific immune responses. The trafficking pattern of iDC and mDC is based on their expression of functional chemotactic receptors and the in vivo sites expressing the corresponding ligands including chemokines and/or classical chemoattractants. In this study, we have evaluated the expression of the formyl peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond chemotactically and by Ca(2+) mobilization to N-formyl-Met-Leu-Phe and a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC express FPRL2 mRNA and protein. As mDC do not express any other members of the human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and maintain its expression even after maturation, suggesting that the interaction of FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking during Ag uptake and processing in the periphery as well as the T cell-stimulating phase of the immune responses.}, } @article {pmid12218207, year = {2002}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Characteristics of tumors in lymph vessels play an important role in the tumor progression of invasive ductal carcinoma of the breast: a prospective study.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {9}, pages = {904-913}, doi = {10.1097/01.MP.0000024289.59262.CE}, pmid = {12218207}, issn = {0893-3952}, mesh = {Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal, Breast/mortality/*pathology ; Cell Division ; Disease Progression ; Female ; Humans ; Lymphatic Metastasis ; Lymphatic System/pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating/*pathology ; Prospective Studies ; Risk Factors ; }, abstract = {It is unknown whether the characteristics of tumor cells in lymph vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast. The purpose of this study was to investigate the significance of the characteristics of tumor cells in the lymph vessels in relation to the tumor progression in 393 IDC patients in comparison with well-known histological parameters. The dimensions of lymph vessel tumor emboli were measured, and their structural features, nuclear atypia, and numbers of mitotic and apoptotic figures were also assessed. Multiple regression analysis showed the dimension, the distance, the number of mitotic figures, the number of apoptotic figures, and papillary features of lymph vessel tumor emboli to be significantly associated with the increased number of cells invading the lymph vessels (P < .05). The Cox proportional hazard multivariate analyses showed that more than six apoptotic figures in lymph vessel tumor emboli significantly increased the hazard rates (HRs) of tumor recurrence and death in IDCs without nodal metastasis and that more than four mitotic figures in lymph vessel tumor emboli significantly increased the HRs of tumor recurrence and death in IDCs with nodal metastasis (P < .05). The present study showed that the histological characteristics of tumor cells in lymph vessels play a very important role in the tumor progression of IDCs.}, } @article {pmid12217024, year = {2002}, author = {Simon, U and Sanders, D and Jockel, J and Heppel, C and Brinz, T}, title = {Design strategies for multielectrode arrays applicable for high-throughput impedance spectroscopy on novel gas sensor materials.}, journal = {Journal of combinatorial chemistry}, volume = {4}, number = {5}, pages = {511-515}, doi = {10.1021/cc020025p}, pmid = {12217024}, issn = {1520-4766}, abstract = {This paper reports the first design and fabrication of a 64 multielectrode array for high-throughput impedance spectroscopy. The purpose of this work is the development of a measurement system for the discovery and improvement of sensor materials using combinatorial methods. An array of interdigital capacitors (IDC) screen-printed onto a high-temperature-resistant Al(2)O(3) substrate is determined to be the optimal test plate. The electrode layout, and therefore also the idle capacity, is determined by specific requirements. Calculation of the idle capacity of the IDC as a function of the electrode width and distance allows adjustment and thus optimization of the array. Parasitic effects caused by the leads and contacts are compensated by a software-aided calibration. Apart from the use of the substrates for discovery of new sensor materials, the presented electrode array is also suitable for electrocatalytic applications as well as impedance spectroscopic studies of semiconductors and dielectrics.}, } @article {pmid12215297, year = {2002}, author = {Song, M and Mi, X and Li, B and Zhu, J and Gao, Y and Cui, S and Song, J}, title = {Expression of telomerase genes in cancer development in atypical hyperplasia of the mammary duct.}, journal = {Chinese medical journal}, volume = {115}, number = {8}, pages = {1221-1225}, pmid = {12215297}, issn = {0366-6999}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/pathology ; DNA-Binding Proteins ; Female ; Gene Expression ; Humans ; Precancerous Conditions/*genetics/pathology ; RNA/*genetics/physiology ; RNA, Messenger/analysis ; Telomerase/*genetics/physiology ; }, abstract = {OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation.

METHODS: Expression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer.

RESULTS: The expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%). The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypical hyperplasia and intraductal carcinoma was not significant (P > 0.05).

CONCLUSION: Telomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.}, } @article {pmid12203362, year = {2002}, author = {Mercapide, J and Zhang, SY and Fan, X and Furió-Bacete, V and Schneider, J and López de la Osa, I and Patchefsky, AS and Klein-Szanto, AJ and Castresana, JS}, title = {CCND1- and ERBB2-gene deregulation and PTEN mutation analyses in invasive lobular carcinoma of the breast.}, journal = {Molecular carcinogenesis}, volume = {35}, number = {1}, pages = {6-12}, doi = {10.1002/mc.10069}, pmid = {12203362}, issn = {0899-1987}, support = {CA-06927/CA/NCI NIH HHS/United States ; CA-71539/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; *Cell Cycle Proteins ; Cyclin D1/*genetics ; DNA Mutational Analysis ; *DNA-Binding Proteins ; E2F Transcription Factors ; E2F1 Transcription Factor ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Ki-67 Antigen/metabolism ; Neoplasm Invasiveness/genetics ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases/*genetics ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Receptor, ErbB-2/*genetics ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/*genetics ; }, abstract = {Because of the relatively low incidence of lobular breast carcinoma, there are very few studies on the molecular characteristics of this breast cancer. In an attempt to improve its characterization, we investigated in a large collection of invasive lobular carcinomas (ILCs) the status of markers known to be involved in the better-studied invasive ductal carcinomas (IDC). In the current study we disposed of 80 well-characterized ILC cases. Gene amplification of cyclin D1 (CCND1) and c-erbB2-encoding gene (ERBB2) and expression of their gene products were studied by differential polymerase chain reaction (PCR) and immunohistochemistry, respectively. A comprehensive point mutation study of the phosphatase and tensin homolog tumor suppressor gene (PTEN) was pursued by single strand conformation polymorphism (SSCP)/sequencing analysis. The CCND1 gene was rarely amplified in ILC in spite of showing overexpression of the protein in 41% of tumors. Hence, unlike IDC, increase in gene dosage did not account for the protein excess. PTEN mutations were detected in ILC (truncating mutations) in around 2% of the tumors. Unlike IDC, ILC did not display ERBB2 overexpression and expression of the transcription factor E2F1 correlated inversely with tumor grade. The observed discrepancy in the pattern of the human oncogenes CCND1 and ERBB2, which are involved in the process of carcinogenesis of ductal tumors, appears to suggest a different molecular basis for development and progression of ILC.}, } @article {pmid12199756, year = {2002}, author = {Roorda, AK and Hansen, JP and Rider, JA and Huang, S and Rider, DL}, title = {Ectopic breast cancer: special treatment considerations in the postmenopausal patient.}, journal = {The breast journal}, volume = {8}, number = {5}, pages = {286-289}, doi = {10.1046/j.1524-4741.2002.08507.x}, pmid = {12199756}, issn = {1075-122X}, mesh = {Aged ; Breast Neoplasms/*diagnosis/pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology/therapy ; *Choristoma ; Diagnosis, Differential ; Female ; Humans ; *Nipples ; Postmenopause ; }, abstract = {A 70-year-old woman with congenital bilateral accessory nipples developed a clinical mass and pain in the left accessory breast tissue. Excision revealed a T2 invasive ductal carcinoma with an identifiable in situ component. No masses were present in the normal breast, and 9 years after surgery, radiation therapy, and tamoxifen there has been no recurrence either in the ipsilateral affected accessory or normal breast tissue.}, } @article {pmid12196721, year = {2002}, author = {Matsuo, K and Fukutomi, T and Hasegawa, T and Akashi-Tanaka, S and Nanasawa, T and Tsuda, H}, title = {Histological and immunohistochemical analysis of apocrine breast carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {9}, number = {1}, pages = {43-49}, doi = {10.1007/BF02967546}, pmid = {12196721}, issn = {1340-6868}, mesh = {Adult ; Aged ; Apocrine Glands/*pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Case-Control Studies ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Hormone-Dependent ; Paraffin Embedding ; Receptors, Estrogen ; Receptors, Progesterone ; Retrospective Studies ; }, abstract = {BACKGROUND: There are few data regarding the biological characteristics of apocrine breast carcinoma in the literature due to its rarity and controversy over its definition. We analyzed the histopathological characteristics and tumor biology of apocrine breast carcinomas with regard to histological grade, p53, HER2, bcl-2, MIB-1 and hormone receptor status.

PATIENTS AND METHODS: A consecutive series of 24 female apocrine breast carcinoma patients were the primary source of these retrospective data. Background factors including histological grade, nodal status and lymphatic invasion by tumor cells were analyzed. Immunohistochemical staining for p53, HER2, MIB-1, bcl-2, estrogen receptor (ER) and progesterone receptor (PR) was carried out on formalin-fixed, paraffin embedded specimens.

RESULTS: Older age and postmenopausal status were observed more frequently in patients with apocrine breast carcinoma than those with invasive ductal carcinoma. Apocrine breast carcinoma also showed relatively lower histological grade than invasive ductal carcinoma. Nuclear accumulation of p53, HER2 overexpression, bcl-2 and MIB-1 index were observed in 29% (7/24), 33%(8/24), 25%(6/24) and 29% (7/24) of cases, respectively. Positivity for ER and PR was present in 17% (4/24) and 17% (4/24) of cases, respectively.

CONCLUSIONS: Apocrine breast carcinoma tended to show low MIB-1 index, low bcl-2 expression and low positive rate of hormone receptors. There was no correlation between the three types of apocrine carcinoma and the positivity rate of p53, HER2, bcl-2, MIB-1 and hormone receptor status.}, } @article {pmid12188412, year = {2002}, author = {Lertsanguansinchai, P and Chottetanaprasith, T and Chatamra, K and Sampatanukul, P and Wannakrairot, P and Rojpornpradit, P and Shotelersuk, K and Lertbutsayanukul, C and Boonjunwetwat, D and Vajragupta, L}, title = {Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at King Chulalongkorn Memorial Hospital.}, journal = {Journal of the Medical Association of Thailand = Chotmaihet thangphaet}, volume = {85 Suppl 1}, number = {}, pages = {S193-202}, pmid = {12188412}, issn = {0125-2208}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Climacteric ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Postmenopause ; Prognosis ; Receptors, Estrogen/analysis/*metabolism ; Receptors, Progesterone/analysis/*metabolism ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {A retrospective review was performed on 576 patients who have been diagnosed breast cancer and referred to Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between January 1995-September 2001. There were three hundred ninety nine cases of invasive breast cancer that available for estrogen (ER) and/or progesterone (PR) receptor status. The mean and median age in our study were 49.6 year and 49.0 year respectively. About 60.9 per cent of the patients were pre and peri-menopause and 37.8 per cent were post-menopause. Most of the histological cell type were invasive ductal carcinoma which comprised of 92.7 per cent. Histologic grading were nearly equal for moderately and poorly differentiated grade: 43.66 per cent and 40.66 per cent. The results of our study showed 53.4 per cent of 399 patients had ER positive and 42.1 per cent of 380 patients had PR positive. The proportion of ER+PR+, ER+PR-, ER-PR+, and ER-PR- were 36.31 per cent, 15.53 per cent, 5.79 per cent and 42.37 per cent respectively. Older age and post-menopause women had higher ER+. While patients with increase tumor size, poorly differentiated grading, increase positivity of axillary lymph nodes and higher stage have more chance of ER negative and PR negative.}, } @article {pmid12185332, year = {2002}, author = {Wang, X and Mori, I and Tang, W and Nakamura, M and Nakamura, Y and Sato, M and Sakurai, T and Kakudo, K}, title = {p63 expression in normal, hyperplastic and malignant breast tissues.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {9}, number = {3}, pages = {216-219}, doi = {10.1007/BF02967592}, pmid = {12185332}, issn = {1340-6868}, mesh = {Biopsy, Needle ; Breast Diseases/genetics/pathology ; Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Culture Techniques ; Diagnosis, Differential ; Female ; Gene Expression Regulation ; Genes, Tumor Suppressor ; Genes, p53/*genetics ; *Genetic Predisposition to Disease ; Humans ; Hyperplasia/*genetics/pathology ; Immunohistochemistry ; Probability ; Reference Values ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study.

METHODS: Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining.

RESULTS: p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas.

CONCLUSION: The results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.}, } @article {pmid12182452, year = {2002}, author = {Ruwhof, C and Canning, MO and Grotenhuis, K and de Wit, HJ and Florencia, ZZ and de Haan-Meulman, M and Drexhage, HA}, title = {Accessory cells with a veiled morphology and movement pattern generated from monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.}, journal = {Immunobiology}, volume = {205}, number = {3}, pages = {247-266}, doi = {10.1078/0171-2985-00129}, pmid = {12182452}, issn = {0171-2985}, mesh = {Antigen-Presenting Cells/cytology/immunology/*physiology ; Cell Adhesion/drug effects ; Cell Movement/drug effects/*physiology ; Dendritic Cells/cytology/immunology/*physiology ; Enzyme Activation/physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Monocytes/cytology/immunology/physiology ; NADPH Oxidases/*metabolism ; }, abstract = {Veiled cells (VC) present in afferent lymph transport antigen from the periphery to the draining lymph nodes. Although VC in lymph form a heterogeneous population, some of the cells clearly belong on morphological grounds to the Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and avoiding the activation of NADPH oxidase (blocking agents) results in the generation of a population of veiled accessory cells. The generated VC were actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/-) VC were as good in stimulating allogeneic T cell proliferation as immature DC (iDC) obtained after one week of adherent culture of monocytes in granulocyte-macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This underscores the accessory cell function of the mo-derived CD14(dim/-) VC. Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83 and were positive for S100, expression of the DC-specific markers CD1a, Langerin, DC-SIGN, and DC-LAMP were absent. This indicates that the here generated CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances, gaining some macrophage characteristics before dying. The IL-12 production from mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher as compared to iDC. Consequently the T cells that were stimulated by these mo-derived VC produced less IFN-gamma as compared with T cells stimulated by iDC. Our data indicate that it is possible to rapidly generate a population of CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and cytokine production of these VC indicate that this population is not a classical DC population. The cells might earlier be related to the veiled macrophage-like cells also earlier described in afferent lymph.}, } @article {pmid12181128, year = {2002}, author = {Todor, A and Sharov, VG and Tanhehco, EJ and Silverman, N and Bernabei, A and Sabbah, HN}, title = {Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {283}, number = {3}, pages = {H990-5}, doi = {10.1152/ajpheart.01003.2001}, pmid = {12181128}, issn = {0363-6135}, support = {HL-49090-07/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Apoptosis ; Apoptosis Regulatory Proteins ; Cardiomyopathy, Dilated/metabolism/pathology ; Caspase 3 ; Caspases/*metabolism ; Female ; Heart Failure/*metabolism/pathology ; Humans ; Hypoxia/*metabolism ; In Vitro Techniques ; Male ; Middle Aged ; Muscle Fibers, Skeletal/enzymology/pathology ; Myocardial Ischemia/metabolism/pathology ; Myocardium/*metabolism/pathology ; Proteins/*metabolism ; }, abstract = {It has been proposed that the hemodynamic deterioration associated with heart failure (HF) may be due in part to ongoing loss of viable cardiac myocytes through apoptosis. Hypoxia has been shown to promote apoptosis in normal cardiomyocytes. Adaptation and maladaptations inherent to heart failure can modify the susceptibility of cells to different stress factors. We hypothesized that HF modifies the threshold of cardiomyocytes to hypoxia-induced apoptosis. Cardiomyocytes were isolated from 18 human hearts explanted at the time of cardiac transplantation due to either ischemic cardiomyopathy (ICM) (n = 9) or idiopathic dilated cardiomyopathy (IDC) (n = 9). Tissue from five normal donor hearts (NL) for whom no suitable recipient was available was used as control. Cardiomyocytes were incubated for 3 h under normoxic (95% air-5% CO(2)) or hypoxic (95% N(2)-5% CO(2)) conditions. Expression of caspase-3 and DNA fragmentation factor-45 (DFF45)/inhibitor of caspase-3-activated DNase (ICAD) was detected by Western blot analysis. Three hours of hypoxia did not affect the expression of these proteins in NL cardiomyocytes. In contrast, hypoxia led to cleavage of caspase-3 and DFF45/ICAD both in ICM and IDC. In conclusion, failing cardiomyocytes exhibit increased susceptibility to hypoxia-induced apoptosis.}, } @article {pmid12177657, year = {2002}, author = {Adamopoulos, S and Parissis, JT and Georgiadis, M and Karatzas, D and Paraskevaidis, J and Kroupis, C and Karavolias, G and Koniavitou, K and Kremastinos, DT}, title = {Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.}, journal = {American heart journal}, volume = {144}, number = {2}, pages = {359-364}, doi = {10.1067/mhj.2002.124052}, pmid = {12177657}, issn = {1097-6744}, mesh = {Adult ; Aged ; Apoptosis ; Cardiomyopathy, Dilated/*complications ; Cross-Over Studies ; Cytokines/blood ; Female ; Growth Hormone/*administration & dosage ; Heart Failure/*blood/*drug therapy/etiology ; Humans ; Injections, Subcutaneous ; Interleukin-6/*blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha/*analysis ; }, abstract = {BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC).

METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% +/- 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo(2)max) was also used to evaluate the functional status of patients with IDC.

RESULTS: Treatment with GH produced a significant reduction in serum levels of TNF-alpha (8.2 +/- 1.2 vs 5.7 +/- 1.1 pg/mL, P <.05), sTNF-RI (3.9 +/- 0.4 vs 3.2 +/- 0.3 ng/mL, P <.05), sTNF-RII (2.6 +/- 0.3 vs 2.2 +/- 0.2 ng/mL, P <.05), IL-6 (5.5 +/- 0.6 vs 4.4 +/- 0.4 pg/mL, P =.05), sIL-6R (32.7 +/- 3.0 vs 28.2 +/- 3.0 ng/mL, P <.05), sFas (4.4 +/- 0.8 vs 3.1 +/- 0.6 ng/mL, P <.05), and sFasL (34.2 +/- 11.7 vs 18.8 +/- 7.3 pg/mL, P <.01). A significant improvement was also observed in VO2max after the completion of 3 months' treatment with GH (15.0 +/- 0.8 vs 17.2 +/- 1.0 mL/kg/min, P <.05). Good correlations were found between GH-induced reduction in TNF-alpha levels and increase in VO2max (r = -0.64, P <.05) as well as between GH-induced reduction in sFasL and increase in VO2max (r = -0.56, P =.08).

CONCLUSIONS: GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC.}, } @article {pmid12171884, year = {2002}, author = {Yamasawa, K and Nio, Y and Dong, M and Yamaguchi, K and Itakura, M}, title = {Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {8}, number = {8}, pages = {2563-2569}, pmid = {12171884}, issn = {1078-0432}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/*metabolism/mortality ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA Repair ; Exons ; Female ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; Male ; Middle Aged ; Multivariate Analysis ; Mutation ; Pancreatic Neoplasms/*genetics/*metabolism/mortality ; Point Mutation ; *Protein Biosynthesis ; Proteins/*genetics ; Sequence Analysis, DNA ; Sex Factors ; Time Factors ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {PURPOSE: The growth arrest and DNA damage-inducible 45 gene (GADD45a) is one of the downstream mediators of the p53 gene that stimulates DNA excision repair. The present study was designed to assess the clinicopathological significance of GADD45a and p53 in resectable invasive ductal carcinomas (IDCs) of the pancreas.

EXPERIMENTAL DESIGN: This study included 72 pancreatic IDC patients who received surgery between 1982 and 2001. Point mutations in exons 1 and 4 of GADD45a and the expression of the GADD45a gene product (Gadd45) and p53 protein were analyzed by direct DNA sequencing and immunohistochemistry.

RESULTS: Point mutations were found in exon 4 of GADD45a in eight cases (13.6%). Gadd45 and p53 were expressed in 54.2% (39 of 72) and 47.2% (34 of 72) of the patients. The expression of Gadd45 did not necessarily correlate with that of p53. However, Gadd45 expression correlated significantly with the grade of the pT factor of the tumors. Coexpression analysis of Gadd45 and p53 indicated that in patients with p53(+) IDC, the Gadd45(+) group had a significantly lower survival rate than the Gadd45(-) group. Furthermore, Gadd45 expression had no effect on the efficacy of the adjuvant chemotherapy. Multivariate analysis indicated that pTNM (tumor-node-metastasis) stage, grade, and adjuvant chemotherapy were significant variables for survival. Furthermore, in the p53(-) group, there were no significant variables. In contrast, in the p53(+) group, pTNM stage, histological grade, and Gadd45 expression were significant variables.

CONCLUSIONS: The frequency of GADD45a mutation is appreciable in human pancreatic IDC, and the expression of Gadd45, combined with that of p53, significantly affects the survival of patients with resectable IDCs of the pancreas.}, } @article {pmid12168058, year = {2002}, author = {Ben-Hur, H and Mordechay, E and Halperin, R and Gurevich, P and Zandbank, J and Herper, M and Zusman, I}, title = {Apoptosis-related proteins (Fas, Fas ligand, bcl-2 and p53) in different types of human breast tumors.}, journal = {Oncology reports}, volume = {9}, number = {5}, pages = {977-980}, pmid = {12168058}, issn = {1021-335X}, mesh = {Apoptosis ; Breast Neoplasms/blood/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood/metabolism ; Carcinoma, Intraductal, Noninfiltrating/blood/metabolism ; Disease Progression ; Epithelial Cells/metabolism ; Fas Ligand Protein ; Female ; Fibroadenoma/blood/metabolism ; Humans ; Immunohistochemistry ; Lymphocytes/metabolism ; Membrane Glycoproteins/*biosynthesis/blood ; Proto-Oncogene Proteins c-bcl-2/*biosynthesis/blood ; Time Factors ; Tumor Suppressor Protein p53/*biosynthesis/blood ; fas Receptor/*biosynthesis/blood ; }, abstract = {The aim of this study was to evaluate the possible role of apoptosis-related proteins (ARP: Fas and Fas ligand, bcl-2, p53) in the progress of tumorigenesis in breast cancer. Epithelial tumor cells and lymphocytes were analyzed immunohistochemically for the rate of lymphoid infiltration and presence of ARP in 50 human breast tumors of different types. The tumors included: i) fibrocystic disease (n=12); ii) benign fibroadenoma (n=11); iii) carcinoma in situ (n=8); iv) invasive ductal carcinoma with high lymphoid infiltration (n=12); and v) invasive ductal carcinoma with lymphoid depletion (n=7). Both fibrocystic disease and fibroadenomas had low amounts of lymphocytes and very little lymphoid infiltration. In cancer in situ, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a rise in the total number of lymphocytes, reflecting intensification of the immune response. In carcinomas with high lymphoid infiltration, a significant increase in the number of Fas and FasL and p53-positive cells was found. The number of bcl-2-positive tumor cells in these tumors was not changed, whereas the number of bcl-2-positive lymphocytes decreased. In carcinomas with lymphoid depletion, the opposite picture was found as a result of deep subcompensation of the lymph system. ARP are present in a significantly higher number of lymphocytes than of the epithelial tumor cells. This indicates that the cells initiating apoptosis in tumors are themselves damaged by the process. The intense apoptosis in lymphocytes in malignant tumors may be one of the reasons for the progress of breast tumors.}, } @article {pmid12165659, year = {2002}, author = {Kimura, N and Yoshida, R and Shiraishi, S and Pilichowska, M and Ohuchi, N}, title = {Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma.}, journal = {Endocrine pathology}, volume = {13}, number = {2}, pages = {117-122}, pmid = {12165659}, issn = {1046-3976}, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Chromogranin A ; Chromogranin B ; Chromogranins/*metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Lymphatic Metastasis/pathology ; Neoplasm Invasiveness ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; }, abstract = {Recent progress in the study of chromogranins has revealed that there are many novel peptides derived from chromogranin with their multiple pathophysiologic roles. To learn the possible roles of chromogranin in breast carcinoma, we immunohistochemically investigated tissue localization of chromogranin A (CgA) and chromogranin B (CgB) in 10 normal breast tissues, 23 noninvasive ductal carcinomas (NIDCs), and 169 invasive ductal carcinomas (IDCs) and compared their expression with estrogen receptor (ER), progesterone receptor (PR), and Ki67. CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion. The expression of CgA and CgB was higher in NIDCs than in IDCs: CgA = 70% of NIDC vs 22% of IDC and CgB = 65% of NIDC vs 30% of IDC. There was a statistical correlation between the expression of CgA and PR (p < 0.05) and CgB and ER (p < 0.05) in IDCs without lymph node metastasis. On the other hand, there was a significant correlation between expression of CgB and PR and an inverse correlation between CgA and Ki67 in IDCs of overall cases. The data suggest that CgA and CgB may play some role in the early phase of neoplastic progression.}, } @article {pmid12165506, year = {2002}, author = {Coronella, JA and Spier, C and Welch, M and Trevor, KT and Stopeck, AT and Villar, H and Hersh, EM}, title = {Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {169}, number = {4}, pages = {1829-1836}, doi = {10.4049/jimmunol.169.4.1829}, pmid = {12165506}, issn = {0022-1767}, support = {1R03AG20314-01/AG/NIA NIH HHS/United States ; 5F32CA79115-04/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Antigens, Neoplasm/*metabolism ; B-Lymphocytes/*immunology/pathology ; Breast Neoplasms/*immunology/pathology ; Carcinoma, Ductal, Breast/*immunology/pathology ; Female ; Genes, Immunoglobulin ; Germinal Center/immunology/pathology ; Humans ; Immunoglobulin Fab Fragments/metabolism ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/*immunology/pathology ; Mutation ; Peptide Library ; Tumor Cells, Cultured ; }, abstract = {The objective of this study was to determine whether tumor-infiltrating B cells (TIL-B) of infiltrating ductal carcinoma (IDC) of the breast represent a tumor-specific humoral immune response. Immunohistochemical analysis of three Her-2/neu-negative IDC tumors from geriatric patients showed that TIL-B cluster in structures similar to germinal centers containing CD20(+) B lymphocyte and CD3(+) T lymphocyte zones with interdigitating CD21(+) follicular dendritic cells, suggesting an in situ immune response. A total of 29, 31, and 58 IgG1 H chain clones was sequenced from the three IDC tumors, respectively. Intratumoral oligoclonal expansion of TIL-B was demonstrated by a preponderance (45-68%) of clonal B cells. In contrast, only 7% of tumor-draining lymph node and 0% of healthy donor PBL IgG H chains were clonal, consistent with the larger repertoires of node and peripheral populations. Patterns and levels of TIL-B IgG H chain somatic hypermutation suggested affinity maturation in intratumoral germinal centers. To examine the specificity of TIL-B Ig, a phage-displayed Fab library was generated from the TIL-B of one IDC tumor. Panning with an allogeneic breast cancer cell line enriched Fab binding to breast cancer cells, but not nonmalignant cell lines tested. However, panning with autologous tumor tissue lysate increased binding of Fab to both tumor tissue lysate and healthy breast tissue lysate. These data suggest an in situ Ag-driven oligoclonal B cell response to a variety of tumor- and breast-associated Ags.}, } @article {pmid12162965, year = {2002}, author = {Barbosa Pereira, PJ and Segura-Martín, S and Oliva, B and Ferrer-Orta, C and Avilés, FX and Coll, M and Gomis-Rüth, FX and Vendrell, J}, title = {Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI).}, journal = {Journal of molecular biology}, volume = {321}, number = {3}, pages = {537-547}, doi = {10.1016/s0022-2836(02)00648-4}, pmid = {12162965}, issn = {0022-2836}, mesh = {Amino Acid Sequence ; Binding Sites ; Carboxypeptidase B ; Carboxypeptidase B2/*pharmacology ; Carboxypeptidases/antagonists & inhibitors/*chemistry ; Enzyme Precursors/antagonists & inhibitors/*chemistry ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Recombinant Proteins/antagonists & inhibitors/chemistry ; Sequence Homology, Amino Acid ; }, abstract = {Besides their classical role in alimentary protein degradation, zinc-dependant carboxypeptidases also participate in more selective regulatory processes like prohormone and neuropeptide processing or fibrinolysis inhibition in blood plasma. Human pancreatic procarboxypeptidase B (PCPB) is the prototype for those human exopeptidases that cleave off basic C-terminal residues and are secreted as inactive zymogens. One such protein is thrombin-activatable fibrinolysis inhibitor (TAFI), also known as plasma PCPB, which circulates in human plasma as a zymogen bound to plasminogen. The structure of human pancreatic PCPB displays a 95-residue pro-segment consisting of a globular region with an open-sandwich antiparallel-alpha antiparallel-beta topology and a C-terminal alpha-helix, which connects to the enzyme moiety. The latter is a 309-amino acid residue catalytic domain with alpha/beta hydrolase topology and a preformed active site, which is shielded by the globular domain of the pro-segment. The fold of the proenzyme is similar to previously reported procarboxypeptidase structures, also in that the most variable region is the connecting segment that links both globular moieties. However, the empty active site of human procarboxypeptidase B has two alternate conformations in one of the zinc-binding residues, which account for subtle differences in some of the key residues for substrate binding. The reported crystal structure, refined with data to 1.6A resolution, permits in the absence of an experimental structure, accurate homology modelling of TAFI, which may help to explain its properties.}, } @article {pmid12161228, year = {2002}, author = {Richartz, BM and Werner, GS and Ferrari, M and Figulla, HR}, title = {Comparison of left ventricular systolic and diastolic function in patients with idiopathic dilated cardiomyopathy and mild heart failure versus those with severe heart failure.}, journal = {The American journal of cardiology}, volume = {90}, number = {4}, pages = {390-394}, doi = {10.1016/s0002-9149(02)02495-5}, pmid = {12161228}, issn = {0002-9149}, mesh = {Analysis of Variance ; Cardiomyopathy, Dilated/*complications/diagnostic imaging/physiopathology ; Diastole ; Echocardiography, Doppler ; Female ; Heart Failure/complications/diagnostic imaging/physiopathology ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulmonary Edema/*etiology ; Regression Analysis ; Systole ; Ventricular Dysfunction, Left/complications/diagnostic imaging/physiopathology ; }, abstract = {The pathogenesis of acute pulmonary edema in idiopathic dilated cardiomyopathy (IDC) is not completely understood. Because pulse-wave tissue Doppler imaging (TDI) allows a direct comparison between systolic as well as diastolic wall motion velocities, we tested the hypothesis that acute pulmonary edema is caused by both systolic and diastolic failure. We prospectively studied 65 patients. Forty patients had IDC (group 1), 15 of whom had recent-onset pulmonary congestion (group 1a, New York Heart Association [NYHA] functional classes III and IV) and 25 of whom were in clinically stable condition without signs of pulmonary congestion (group 1b, NYHA I and II). All of these patients were restudied after 3, 7, and 45 days. Groups 1a and 1b were compared with 25 subjects without evidence of heart disease (group 2). Peak systolic wall motion velocity (Vs), peak wall motion velocity of the early (Ve), and late (Va) filling waves were measured by TDI; mitral inflow pattern was determined by pulse-wave Doppler and left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography. In those patients without pulmonary edema (controls and group 1b, n = 50), we found a positive correlation between LVEF and Vs (r = 0.72, p <0.001) and between LVEF and Ve (r = 0.79, p <0.001). Early diastolic wall motion velocity always exceeded peak systolic wall motion velocity (Ve/Vs ratio >1). In patients with IDC with recent-onset pulmonary congestion (group 1a), Ve was significantly lower compared with group 1b (3.5 +/- 0.2 vs 4.9 +/- 0.4 cm/s, p <0.01, Ve/Vs ratio <1). Clinical improvement was paralled by a gradual increase in Ve (3.5 +/- 0.2 to 6.8 +/- 0.3 cm/s, p <0.01) but not in Vs or LVEF. Thus, in patients with IDC acute pulmonary edema is exclusively caused by diastolic rather than systolic failure.}, } @article {pmid12152162, year = {2002}, author = {Thor, AD and Eng, C and Devries, S and Paterakos, M and Watkin, WG and Edgerton, S and Moore, DH and Etzell, J and Waldman, FM}, title = {Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization.}, journal = {Human pathology}, volume = {33}, number = {6}, pages = {628-631}, doi = {10.1053/hupa.2002.124034}, pmid = {12152162}, issn = {0046-8177}, support = {P01 CA44768/CA/NCI NIH HHS/United States ; P53 CA58207/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; *Chromosome Aberrations ; Chromosome Banding ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 17 ; *Chromosomes, Human, Pair 8 ; Female ; Gene Deletion ; Genes, erbB-2/genetics ; Humans ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of invasive ductal carcinoma (IDC) characterized by unique histology and an extremely high incidence of lymph node metastases (approximately 95%). Comparative genomic hybridization (CGH) was used to characterize DNA extracted from 16 archival IMC cases to identify clonal genetic changes associated with this unique and highly metastatic cancer subtype. The average number of chromosomal alterations per IMC tumor was 7.4 +/-2.9 (3.4 gains and 3.9 losses), fewer than the number that we have observed in IDCs not otherwise specified (9.5 +/-6.6), IDCs with erbB-2 gene amplification (12.6 +/-5.9), and invasive lobular carcinomas (8.2 +/-5.5). The mean number of changes in IMC was significantly higher than we have observed in the rarely metastasizing tubular subtype of IDC (3.9 +/-2.3, P = 0.001), but less than the more aggressive subset of erbB-2-amplified IDC (P = 0.02). Remarkably, 100% of IMCs demonstrated loss involving the short arm of chromosome 8 (8p). Six cases showed loss of the entire 8p arm, whereas in 10 cases the loss was limited to the distal portion (8p21-pter) with localized gain of proximal 8p (8p11-p12). A reciprocal gain of 8q was detected in 14 cases (88%). Other common alterations included loss of 17p in 50% of tumors and loss of 16q in 50% of IMC cases. Gains of 17q (38%), 1q (31%), and 16p (25%) were also commonly detected. In comparison, IDCs (not otherwise specified), IDCs of the tubular subtype, and invasive lobular carcinomas showed only modest 8p loss (33%, 28%, and 13%, respectively). This region of chromosome 8 may contain 1 or more genes whose loss leads to this particular histology and/or the lymphotrophic phenotype associated with this histopathologic pattern.}, } @article {pmid12150452, year = {2002}, author = {Zhang, Z and Yamashita, H and Toyama, T and Hara, Y and Omoto, Y and Sugiura, H and Kobayashi, S and Harada, N and Iwase, H}, title = {Semi-quantitative immunohistochemical analysis of aromatase expression in ductal carcinoma in situ of the breast.}, journal = {Breast cancer research and treatment}, volume = {74}, number = {1}, pages = {47-53}, doi = {10.1023/a:1016022314608}, pmid = {12150452}, issn = {0167-6806}, mesh = {Adult ; Age Factors ; Aged ; Antineoplastic Agents, Hormonal/pharmacology ; Aromatase/analysis/*biosynthesis ; Breast Neoplasms/*enzymology/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/*pathology ; Enzyme Inhibitors/pharmacology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; }, abstract = {Although estrogens whose production is catalyzed by aromatase are considered to play a role in human breast carcinogenesis, it remains unclear whether aromatase expression occurs in ductal carcinoma in situ (DCIS) of the breast. Aromatase expression in 61 cases of pure DCIS and 101 cases of invasive ductal carcinoma (IDC) was investigated by immunohistochemical analysis using a polyclonal anti-aromatase antibody. The level of aromatase expression was semiquantified by the H-score which was estimated by the percentage of positive-staining cells and the intensity of staining. The levels of aromatase expression were compared between the DCIS and IDC samples, and were also compared among the tumor cells and stromal cells in the DCIS and IDC samples. Positive cytoplasmic staining for aromatase expression was found not only in stromal cells but also in tumor cells. The levels of aromatase expression in the tumor cells and stromal cells from the DCIS samples were significantly higher than those in the respective cells from the IDC samples. Among the DCIS samples, those specimens from patients of ages 50 years or over showed higher levels of aromatase expression in stromal cells, than those from patients below 50 years. The finding that significantly higher aromatase expression levels were found in DCIS than in IDC indicates that it may be possible to treat DCIS patients with aromatase inhibitors, especially as an adjuvant hormonal therapy for postmenopausal patients.}, } @article {pmid12149801, year = {2002}, author = {Leder, U and Baumert, M and Liehr, M and Schirdewan, A and Figulla, HR and Voss, A}, title = {[Modified interaction of blood pressure and heart rate in idiopathic dilated cardiomyopathy].}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {47}, number = {6}, pages = {151-154}, doi = {10.1515/bmte.2002.47.6.151}, pmid = {12149801}, issn = {0013-5585}, mesh = {Aged ; Autonomic Nervous System/physiopathology ; Blood Pressure/*physiology ; Blood Pressure Monitors ; Cardiac Volume/physiology ; Cardiomyopathy, Dilated/diagnosis/*physiopathology ; Electrocardiography ; Female ; Heart Failure/diagnosis/physiopathology ; Heart Rate/*physiology ; Humans ; Male ; Middle Aged ; Pressoreceptors/physiopathology ; Prognosis ; Stroke Volume/physiology ; Systole/physiology ; }, abstract = {BACKGROUND: Neurovegetative and haemodynamic changes impact on the regulation pattern of blood pressure and heart rate in patients with heart failure. We studied these patterns and their interactions in patients with idiopathic dilated cardiomyopathy (IDC) and in healthy subjects (REF).

METHODS: We continually measured the heart rate and blood pressure (Portapres device) in twenty-five supine IDC patients (age: 51 +/- 13 y; left ventricular end-diastolic diameter 67 +/- 11 mm; ejection fraction 30 +/- 11%) and in twenty-seven REF (age: 50 +/- 11 y) Recording time was 30 minutes. The heart rate (HR) of each beat and the systolic blood pressure (SYS) of the subsequent beat were measured. Code numbers (symbols) were assigned to the beat-to-beat changes in HR and SYS (increase: 1; decrease: 0). The frequencies of the symbols sequences of three successive beats were counted. In this way we obtained a matrix consisting of eight (two to the power of three) HR and SYS combinations: 000, 100, 010, 001, 111, 110, 011 and 101. We then counted the frequencies of the different combinations of the symbol sequences in HR and SYS (2(3) x 2(3) = 64 combinations). The relative frequencies of symbol patterns appearing in HR, SYS and in the combined analysis of HR and SYS, were compared for IDC and REF using the T-test for independent samples.

RESULTS: Significant differences were seen between IDC and REF. The HR patterns 101 and 010 were more frequent in IDC than in REF patients (11.1 +/- 4.7 vs. 7.7 +/- 2.9%, p = 0.003, and 16.1 +/- 6.3 vs. 11.7 +/- 4.9%, p = 0.008). This finding was even more marked in the analysis of the SYS patterns 101 and 010 (11.0 +/- 7.4 vs. 8.2 +/- 2.9%, p < 0.001, and 11.6 +/- 7.4 vs. 5.4 +/- 2.7%, p < 0.001). Non-alternating patterns were more frequent in REF (e.g. 000HR & 111SYS: 4.6 +/- 3.3 vs. 2.9 +/- 2.4%, p = 0.03).

CONCLUSIONS: We demonstrated significant interaction of the regulation patterns of blood pressure and heart rate, as also their interactions in IDC. Opposed changes in HR and SYS mediated by the baroreflex, became superimposed by alternans phenomena in IDC. The pattern analysis of changes in HR and SYS detects these disturbances of neurovegetative short-term control.}, } @article {pmid12144821, year = {2002}, author = {Ellis, PE and Fong, LF and Rolfe, KJ and Crow, JC and Reid, WM and Davidson, T and MacLean, AB and Perrett, CW}, title = {The role of p53 and Ki67 in Paget's disease of the vulva and the breast.}, journal = {Gynecologic oncology}, volume = {86}, number = {2}, pages = {150-156}, doi = {10.1006/gyno.2002.6629}, pmid = {12144821}, issn = {0090-8258}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*analysis ; Middle Aged ; Paget Disease, Extramammary/*chemistry ; Paget's Disease, Mammary/*chemistry ; Prognosis ; Risk Factors ; Tumor Suppressor Protein p53/*analysis ; Vulvar Neoplasms/*chemistry ; }, abstract = {OBJECTIVE: Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma.

METHODS: Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index).

RESULTS: p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%.

CONCLUSION: Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.}, } @article {pmid12138231, year = {2002}, author = {Shimizu, Y and Yasui, K and Yamao, K and Ohhashi, K and Kato, T and Yamamura, Y and Hirai, T and Kodera, Y and Kanemitsu, Y and Ito, S and Yanagisawa, A}, title = {Possible oncogenesis of mucinous cystic tumors of the pancreas lacking ovarian-like stroma.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {2}, number = {4}, pages = {413-420}, doi = {10.1159/000065090}, pmid = {12138231}, issn = {1424-3903}, mesh = {Adenoma/diagnosis/*metabolism/*pathology ; Aged ; Carcinoma/diagnosis/*metabolism/*pathology ; Cholangiopancreatography, Endoscopic Retrograde ; Female ; Humans ; Male ; Middle Aged ; Mucins/*metabolism ; Neoplasm Invasiveness ; Ovary/pathology ; Pancreatic Neoplasms/diagnosis/*metabolism/*pathology ; Stromal Cells/pathology ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {BACKGROUND/AIMS: Clinicopathological features and postoperative results from mucinous cystic tumors of the pancreas (MCTs) were reviewed. MCTs with ovarian-like stroma (MCTs-OLS+; n = 6) and those lacking ovarian-like stroma (MCTs-OLS-; n = 4) were compared to elucidate the oncogenesis of MCT without OLS.

PATIENTS AND METHODS: Ten patients with MCT were studied.

RESULTS: The 6 MCTs-OLS+ cases occurred in females and were located in the body and tail of the pancreas. The mean tumor size was 6.5 cm (range 2-11 cm). The majority (5/6) of MCTs-OLS+ were multilocular and exhibited tiny loculi on the cyst wall and septum characteristic of MCTs-OLS+. Pathological classifications were adenoma in 4 patients and noninvasive adenocarcinoma in 2 patients. All 6 patients were alive without tumor recurrence 6-124 months after tumor resection. Of the 4 MCTs-OLS- cases, 2 were males and 2 females; MCTs- OLS- were located in the tail of the pancreas. The mean tumor size was 6.9 cm (range 4-8.4 cm). Invasive cancer in the pancreatic parenchyma or extrapancreatic tissue was recognized in all 4 patients, and the pathological classification of epithelia of the cyst wall were adenocarcinomas. These findings were also compatible with common invasive ductal carcinomas of the pancreas with secondary retention cyst on pseudocyst. All patients died of the disease (15, 27, 31 and 80 months after resection, respectively). Whether or not OLS is specific for MCTs of the pancreas should be clarified in future studies.

CONCLUSION: The results of our study led to three hypotheses regarding the oncogenesis of MCTs-OLS-: (1) MCTs in which OLS disappears during the development of invasive carcinoma; (2) advanced cancer derived from intraductal papillary mucinous tumor of the pancreas, and (3) invasive ductal carcinoma of the pancreas with secondary cyst.}, } @article {pmid12132871, year = {2001}, author = {Swede, H and Moysich, KB and Freudenheim, JL and Quirk, JT and Muti, PC and Hurd, TC and Edge, SB and Winston, JS and Michalek, AM}, title = {Breast cancer risk factors and HER2 over-expression in tumors.}, journal = {Cancer detection and prevention}, volume = {25}, number = {6}, pages = {511-519}, pmid = {12132871}, issn = {0361-090X}, support = {P30 CA16056/CA/NCI NIH HHS/United States ; R25 CA1820/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Breast Neoplasms/*etiology/*metabolism ; Contraceptives, Oral ; Female ; Humans ; Immunoenzyme Techniques ; Menarche ; Menopause ; Menstrual Cycle ; Parity ; Receptor, ErbB-2/*metabolism ; Risk Factors ; }, abstract = {Few epidemiologic studies have investigated the potential role of HER2 in the etiology of breast cancer. We conducted a case-case study of 156 women with incident, invasive ductal carcinoma. Multivariate unconditional logistic regression was used to estimate the odds ratios for a HER2 positive tumor in relation to known and putative risk factors of breast cancer. HER2 status was detected by immunohistochemistry on archival tissue. HER2 positive breast cancers tended to be larger and were less likely to express estrogen receptors, and the incidence rate was higher in patients less than 40 years old. We observed an association between a self-reported history of benign breast disease and the occurrence of HER2 positive breast cancer (OR, 2.1;95% CI, 1.1-4.1). We did not detect associations between HER2 over-expression and family history of breast cancer, parity, late age at first birth, ever having breast fed an infant, or oral contraceptive use. Our findings merit consideration in light of recent evidence of HER2 amplification or over-expression in benign breast disease. Should the link to breast cancer be established, HER2 positive benign breast disease could potentially serve as an early marker for preventive intervention.}, } @article {pmid12118114, year = {2002}, author = {Kleer, CG and Tseng, MD and Gutsch, DE and Rochford, RA and Wu, Z and Joynt, LK and Helvie, MA and Chang, T and Van Golen, KL and Merajver, SD}, title = {Detection of Epstein-Barr virus in rapidly growing fibroadenomas of the breast in immunosuppressed hosts.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {7}, pages = {759-764}, doi = {10.1038/modpathol.3880602}, pmid = {12118114}, issn = {0893-3952}, support = {R01 CA77612/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Breast Neoplasms/*virology ; Carcinoma, Ductal, Breast/virology ; DNA, Viral/analysis ; Epstein-Barr Virus Infections/complications/*diagnosis ; Fibroadenoma/*virology ; Herpesvirus 4, Human/*isolation & purification ; Humans ; Immunocompromised Host/*immunology ; Middle Aged ; Polymerase Chain Reaction ; Tumor Virus Infections/complications/*diagnosis ; }, abstract = {Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P =.0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.}, } @article {pmid12115529, year = {2002}, author = {Umekita, Y and Ohi, Y and Sagara, Y and Yoshida, H}, title = {Expression of maspin predicts poor prognosis in breast-cancer patients.}, journal = {International journal of cancer}, volume = {100}, number = {4}, pages = {452-455}, doi = {10.1002/ijc.10500}, pmid = {12115529}, issn = {0020-7136}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*diagnosis/mortality ; Female ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Proteins/*analysis ; Serpins/*analysis ; Survival Rate ; }, abstract = {The tumor suppressor gene maspin has been reported to inhibit the invasiveness and motility of breast cancer cells. It has been reported that maspin is expressed in normal human mammary epithelial cells but is downregulated during cancer progression, and that p53 could induce maspin expression by transcriptional activation. However, to date, the clinical significance of maspin expression and its correlation with p53 protein expression in human breast cancer patients have not been elucidated. One hundred and sixty-eight female patients diagnosed with invasive ductal carcinoma, who had undergone a mastectomy (154 patients) or breast-conserving surgery (14 patients), were followed up for 15-119 months (median: 87 months) postoperatively. Immunoreactivity for maspin and p53 antibodies with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Tumors with more than 20% of positive cells were considered positive for the expression of maspin. The expression of maspin in carcinoma cells was found in 27.4% (46 of 168) and significantly correlated with larger tumor size (p = 0.008), higher histologic grade (p = 0.0001) and positive p53 status (p = 0.003). A significant inverse relationship was observed between the expression of maspin and estrogen receptor (p = 0.0004) or progesterone receptor status (p = 0.02). Univariate analysis by log-rank test revealed a significant association between the expression of maspin and shorter relapse-free survival (p < 0.0001) and overall survival (p < 0.0001). According to Cox's multivariate analysis, the expression of maspin had the most significant effect in relapse-free survival (p < 0.0001) and overall survival (p < 0.0001) followed by lymph node status. In turn, the expression of maspin in 58 cases of ductal carcinoma in situ were also investigated to explore whether the downregulation of maspin through cancer progression are true or not. However, there were no positive cases in our series. These results seem to be contrary to previous reports defining maspin as a tumor suppressor gene. Although more precise characterization of the maspin expression, especially gene analysis is essential, the present investigation suggests that the expression of maspin is not downregulated through malignant progression and that the immunohistochemic detection of maspin in carcinoma cells may be helpful for selecting the group of breast cancer patients with an aggressive phenotype.}, } @article {pmid12113587, year = {2002}, author = {Giani, C and Campani, D and Rasmussen, A and Fierabracci, P and Miccoli, P and Bevilacqua, G and Pinchera, A and Cullen, KJ}, title = {Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters.}, journal = {The International journal of biological markers}, volume = {17}, number = {2}, pages = {90-95}, doi = {10.1177/172460080201700203}, pmid = {12113587}, issn = {0393-6155}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor II/*analysis/genetics ; Middle Aged ; Prognosis ; RNA, Messenger/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.}, } @article {pmid12111516, year = {2002}, author = {Kawada, M and Kondo, S and Okushiba, S and Morikawa, T and Katoh, H}, title = {Reevaluation of the indications for radical pancreatectomy to treat pancreatic carcinoma: is portal vein infiltration a contraindication?.}, journal = {Surgery today}, volume = {32}, number = {7}, pages = {598-601}, doi = {10.1007/s005950200108}, pmid = {12111516}, issn = {0941-1291}, mesh = {Adult ; Aged ; Carcinoma/pathology/*surgery ; Female ; Humans ; Male ; Middle Aged ; *Neoplasm Invasiveness ; Neoplasm Staging ; *Pancreatectomy ; Pancreatic Neoplasms/pathology/*surgery ; Patient Selection ; Portal Vein/*pathology ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; }, abstract = {PURPOSE: Portal vein resection (PVR) has become more widely performed owing to improvements in the perioperative mortality rate. The present study was performed to determine whether portal vein infiltration is a contraindication against radical pancreatectomy for patients with pancreatic carcinoma.

METHODS: Between 1990 and 1997, a total of 66 patients with invasive ductal carcinoma of the pancreas underwent surgical resection at the Department of Surgery II, Hokkaido University Hospital. After the exclusion of those who underwent distal pancreatectomy, the remaining 43 patients were divided into a PVR(+) group (n = 28) and a PVR(-) group (n = 15). The clinicopathological characteristics, morbidity, and mortality were statistically compared between the two groups.

RESULTS: The overall survival rate of the patients who required PVR was not significantly different from that of those who underwent pancreatic resection without PVR.

CONCLUSION: These findings suggest that combined PVR should not be a contraindication to radical pancreatectomy for pancreatic carcinoma with positive vascular invasion.}, } @article {pmid12103265, year = {2002}, author = {Kuoppala, A and Shiota, N and Kokkonen, JO and Liesmaa, I and Kostner, K and Mäyränpää, M and Kovanen, PT and Lindstedt, KA}, title = {Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure.}, journal = {Journal of the American College of Cardiology}, volume = {40}, number = {1}, pages = {119-125}, doi = {10.1016/s0735-1097(02)01928-9}, pmid = {12103265}, issn = {0735-1097}, mesh = {Adult ; Blotting, Western ; Cardiomyopathy, Dilated/metabolism ; Coronary Disease/metabolism ; Down-Regulation ; Female ; Heart Failure/etiology/*metabolism ; Humans ; Male ; Middle Aged ; Myocardium/metabolism ; Nitric Oxide Synthase/biosynthesis ; Nitric Oxide Synthase Type III ; RNA, Messenger/genetics ; Receptor, Bradykinin B2 ; Receptors, Bradykinin/genetics/*metabolism/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Ventricular Function, Left/*physiology ; }, abstract = {OBJECTIVES: We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF).

BACKGROUND: Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF.

METHODS: Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein.

RESULTS: In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts.

CONCLUSIONS: These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.}, } @article {pmid12101816, year = {2001}, author = {Bozkurt, A and Canataroğlu, A and Cetiner, S and Dönmez, Y and Usal, A and Demirtaş, M}, title = {Lymphocyte subsets in patients with idiopathic dilated cardiomyopathy.}, journal = {Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology}, volume = {1}, number = {2}, pages = {98-100}, pmid = {12101816}, issn = {1302-8723}, mesh = {Adult ; CD4-CD8 Ratio ; Cardiomyopathy, Dilated/blood/diagnostic imaging/*immunology ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural/*cytology ; Lymphocyte Subsets/*cytology ; Male ; Middle Aged ; Ultrasonography ; }, abstract = {OBJECTIVE: Although chronic myocardial inflammatory process mediated by viral and autoimmune factors has been postulated in the pathogenesis of idiopathic dilated cardiomyopathy (IDC), the role of autoimmune mechanisms still remains unclear. The aim of the present study was to investigate the rates of various T cell subsets and natural killer (NK) cells in peripheral blood in order to see whether they had a role in the immunoregulation of IDC.

METHODS: The surface markers of peripheral T and B lymphocytes were detected and percentages of pan T and B cells as well as helper (CD4+) and suppressor (CD8+) T lymphocytes subsets in the peripheral blood and their ratio (CD4+/CD8+) were determined in 27 patients with IDC and in 20 healthy controls. NK cell percentage was also studied.

RESULTS: There were no significant differences between IDC and control groups with respect to T and B cell percentages. The percentages of CD4+ T cell subsets were similar in both groups (48.7 +/- 8.7% vs. 43.5 +/- 9.7% respectively; p = 0.107). CD8+ T cell percentage was significantly decreased in patients with IDC than in controls (22.6 +/- 7.7% vs. 28.2 +/- 8.2%, respectively; p = 0.044). CD4+/CD8+ ratio was markedly higher in patients with IDC than controls (2.6 +/- 1.8 vs. 1.6 +/- 0.6, respectively; p = 0.006). There was no significant difference in the NK cell percentage between groups.

CONCLUSION: Decreased CD8+ T cell subset is the cause of increased CD4+/CD8+ ratio, which may imply decreased self-tolerance and an immunoregulatory defect in the pathogenesis of IDC.}, } @article {pmid12099722, year = {2002}, author = {Asano, K and Bohlmeyer, TJ and Westcott, JY and Zisman, L and Kinugawa, K and Good, M and Minobe, WA and Roden, R and Wolfel, EE and Lindenfeld, J and David Port, J and Perryman, MB and Clevel, J and Lowes, BD and Bristow, MR}, title = {Altered expression of endothelin receptors in failing human left ventricles.}, journal = {Journal of molecular and cellular cardiology}, volume = {34}, number = {7}, pages = {833-846}, doi = {10.1006/jmcc.2002.2022}, pmid = {12099722}, issn = {0022-2828}, support = {HL 03404-03/HL/NHLBI NIH HHS/United States ; HL 48013/HL/NHLBI NIH HHS/United States ; HL616401/HL/NHLBI NIH HHS/United States ; }, mesh = {Cell Membrane/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Iodine Radioisotopes ; Myocardium/*metabolism ; RNA, Messenger/metabolism ; Receptors, Endothelin/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Ventricular Dysfunction, Left/*metabolism ; }, abstract = {BACKGROUND: Endothelin signaling is activated in failing human hearts, and may contribute to progressive myocardial dysfunction and remodeling. However, the behavior of endothelin receptor systems (ET(A) and ET(B)) in failing human hearts is not well understood.

METHODS AND RESULTS: (125)[I]-endothelin-1 binding assays conducted in the presence of a non-hydrolyzable guanine nucleotide to uncouple agonist binding demonstrated that membranes prepared from nonfailing left ventricles (LVs) exhibit a mixed pattern of ET(A) (approximately 60%) and ET(B) (approximately 40%) receptor protein expression. Chronic LV failure from either idiopathic dilated (IDC) or ischemic (ISC) cardiomyopathy was accompanied by a significant (P<0.001) increase in ET(A) receptor density, to approximately 80% of the total population, and a significant (P<0.02) decrease in ET(B) receptor density. Ribonuclease protection assays demonstrated an increase in ET(A) mRNA abundance in IDC and ISC LVs, and a significant (P<0.04) increase in ET(B) mRNA abundance in ISC LVs. Enzyme-linked immunoabsorbent assays demonstrated a significant increase in tissue immunoreactive endothelin-1 concentration in IDC (P=0.01) and in IDC+ISC LVs (P=0.02), but receptor subtype protein or mRNA level was not significantly correlated with tissue ET-1 across all LVs. In situ reverse-transcription polymerase chain reaction in LV sections demonstrated that in both failing and nonfailing LVs the ET(A) gene is expressed in cardiac myocytes, vascular smooth muscle and endothelium; the ET(B) gene is expressed in cardiac myocytes, fibroblasts and endothelium; and the prepro-endothelin-1 gene is expressed in myocytes and interstitial cells.

CONCLUSIONS: In chronically failing human LVs, ET(A) receptor density is increased to become the dominant subtype while ET(B) receptor density is decreased. The ET(A), but not the ET(B) density change is accompanied by cognate regulation of mRNA abundance. Both receptor genes and prepro-endothelin-1 are expressed in cardiac myocytes. Finally, based on a lack of correlation with endothelin-1 tissue levels, it is unlikely that the failure-related changes in ET(A) and ET(B) receptor protein and mRNA expression result from homologous regulation by agonist exposure.}, } @article {pmid12097593, year = {2002}, author = {Sanders, RW and de Jong, EC and Baldwin, CE and Schuitemaker, JH and Kapsenberg, ML and Berkhout, B}, title = {Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells.}, journal = {Journal of virology}, volume = {76}, number = {15}, pages = {7812-7821}, pmid = {12097593}, issn = {0022-538X}, mesh = {Cell Communication ; *Cell Differentiation ; Dendritic Cells/cytology/*virology ; HIV Infections/*transmission ; HIV-1/*physiology ; Humans ; Intercellular Adhesion Molecule-1/metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/metabolism ; Phenotype ; T-Lymphocytes/*virology ; }, abstract = {Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.}, } @article {pmid12091685, year = {2002}, author = {Helvie, MA and Bailey, JE and Roubidoux, MA and Pass, HA and Chang, AE and Pierce, LJ and Wilkins, EG}, title = {Mammographic screening of TRAM flap breast reconstructions for detection of nonpalpable recurrent cancer.}, journal = {Radiology}, volume = {224}, number = {1}, pages = {211-216}, doi = {10.1148/radiol.2241010061}, pmid = {12091685}, issn = {0033-8419}, mesh = {Adult ; Aged ; Breast Neoplasms/*diagnostic imaging/prevention & control/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging ; Female ; Humans ; *Mammaplasty ; *Mammography ; Mastectomy ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; *Surgical Flaps ; }, abstract = {PURPOSE: To evaluate findings from routine mammographic screenings in patients with transverse rectus abdominis musculocutaneous (TRAM) flap reconstructions.

MATERIALS AND METHODS: During a 25-month study period, 214 consecutive screening mammograms in 113 asymptomatic women (mean age, 51 years) with TRAM flap reconstructions were obtained. Mastectomies were performed for cancer in 106 (94%) of the 113 women and for prophylaxis in seven (6%). Prospectively, a Breast Imaging Reporting and Data System (BI-RADS) assessment category 1-5 was assigned to each mammogram. Surgical, medical, pathologic, and radiographic records were retrospectively reviewed. CIs were determined by the normal approximation to the binomial distribution.

RESULTS: Seven (3%) of 214 examinations were BI-RADS category 4 or 5. Six (86%) of seven patients underwent biopsy. Two (33%) of these six biopsies demonstrated invasive ductal carcinoma. Cancer detection rate for mammography was 1.9% (two of 106) (95% CI: 0.33%, 7.32%) for women with reconstruction for breast cancer during the 2-year period. One (6%) of 16 BI-RADS category 3 examinations later proved to be invasive ductal carcinoma at follow-up. No interval cancer was discovered in 171 cases of BI-RADS category 1 or 2 examinations with 1-year follow-up. No cancers occurred in women who underwent prophylactic mastectomy. A biopsy positive predictive value of 33% (95% CI: 6%, 76%) was observed.

CONCLUSION: Screening mammography of TRAM flap-reconstructed breasts enables detection of nonpalpable cancer before clinical examination.}, } @article {pmid12090139, year = {2002}, author = {Leder, U and Haueisen, J and Liehr, M and Baier, V and Frankenstein, L and Nowak, H and Figulla, HR}, title = {High frequency intra-QRS signals in idiopathic dilated cardiomyopathy.}, journal = {Biomedizinische Technik. Biomedical engineering}, volume = {47}, number = {5}, pages = {117-123}, doi = {10.1515/bmte.2002.47.5.117}, pmid = {12090139}, issn = {0013-5585}, mesh = {Adult ; Aged ; Bundle-Branch Block/diagnosis/*physiopathology ; Cardiomyopathy, Dilated/diagnosis/*physiopathology ; *Electrocardiography/instrumentation ; Equipment Design ; Female ; Heart Ventricles/physiopathology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Predictive Value of Tests ; Signal Processing, Computer-Assisted/instrumentation ; }, abstract = {We extracted and quantified high frequency intra-QRS signals in idiopathic dilated cardiomyopathy (IDC). In IDC the analysis of late potentials in the terminal QRS complex often fails in predicting clinical events because of intraventricular conduction abnormalities and the absence of a circumscribed arrhythmogenic substrate. Therefore, new approaches are required to assess the electrical state of the myocardium. We investigated 21 patients suffering from IDC with (n = 14) and without (n = 7) bundle branch block. High resolution 31 lead magnetocardiograms were filtered with a 67 point 4th order Savitzky-Golay filter. The difference of the measured and filtered signals was calculated (67-200 Hz). The spatio-temporal properties and the areas under the curves of the resulting high frequency intra-QRS signals (IQCs) were studied. We detected IQCs in all patients. The patients had individual patterns regarding the temporal and spatial properties of the IQCs during depolarisation. The IQCs predominantly appeared in the initial portion of the QRS. The ratios of the areas under the curves of the IQCs and the measured signals were linearly correlated to the left ventricular enddiastolic diameter (r = 0.71, significance 0.0012). In IDC the ventricular depolarization is accompanied by individual spatial and temporal patterns of high frequency intra-QRS signals. They can be studied non-invasively from body surface mapping data with the algorithm used in this study. This provides access to the assessment of the electrical status in patients with IDC.}, } @article {pmid12082640, year = {2002}, author = {Blanco, MJ and Moreno-Bueno, G and Sarrio, D and Locascio, A and Cano, A and Palacios, J and Nieto, MA}, title = {Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.}, journal = {Oncogene}, volume = {21}, number = {20}, pages = {3241-3246}, doi = {10.1038/sj.onc.1205416}, pmid = {12082640}, issn = {0950-9232}, mesh = {Breast Neoplasms/chemistry/*genetics/pathology ; Cadherins/analysis ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology ; Carcinoma, Lobular/chemistry/genetics/pathology ; Cell Differentiation ; Cytoskeletal Proteins/analysis ; DNA-Binding Proteins/analysis/genetics/*physiology ; Desmoplakins ; Disease Progression ; Epithelial Cells/pathology ; Female ; Humans ; Lymphatic Metastasis/*genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/analysis/genetics/*physiology ; Phenotype ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Snail Family Transcription Factors ; *Trans-Activators ; Transcription Factors/analysis/genetics/*physiology ; beta Catenin ; }, abstract = {Snail is a zinc finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a series of human breast carcinomas, we have analysed the expression of Snail and that of molecules of the E-cadherin/catenin complexes. We have also correlated these data with the pathological features of the tumours. We show that Snail expression inversely correlates with the grade of differentiation of the tumours and that it is expressed in all the infiltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. In addition, Snail is expressed in some dedifferentiated tumours with a negative nodal status. Considering that Snail is involved in the induction of the invasive and migratory phenotype in epithelial cells, these results indicate that it is also involved in the progression of breast ductal tumours, where it could additionally serve as a marker of the metastatic potential.}, } @article {pmid12080410, year = {2002}, author = {Carlsson, E and Bosaeus, I and Nordgren, S}, title = {Body composition in patients with an ileostomy and inflammatory bowel disease: validation of bio-electric impedance spectroscopy (BIS).}, journal = {European journal of clinical nutrition}, volume = {56}, number = {7}, pages = {680-686}, doi = {10.1038/sj.ejcn.1601378}, pmid = {12080410}, issn = {0954-3007}, mesh = {Absorptiometry, Photon ; Adult ; Aged ; Body Composition/*physiology ; Body Fluid Compartments/*physiology ; Body Water/*metabolism ; Bromides ; Deuterium Oxide ; *Electric Impedance ; Female ; Humans ; Ileostomy ; Indicator Dilution Techniques ; Inflammatory Bowel Diseases/*physiopathology/surgery ; Male ; Middle Aged ; Reproducibility of Results ; Sex Characteristics ; }, abstract = {OBJECTIVE: To validate bio-electric impedance spectroscopy (BIS) by comparison with other methods for determination of body water compartments in stable subjects with an ileostomy and no or minor small bowel resection for inflammatory bowel disease (IBD).

SUBJECTS: Twenty-one subjects were included, age range 36-65 y (female/male=12/9), Crohn's disease (CD), n=14, ulcerative colitis (UC), n=6 and indeterminate colitis (IDC), n=1.

METHODS: Fluid compartments were assessed by the use of three independent methods: BIS, dual-energy X-ray absorptiometry (DXA) and dilution techniques (DIL); tritiated water (total body water, TBW); and bromide (extracellular water, ECW), respectively. Intra-cellular water (ICW) was calculated as TBW-ECW. For comparison TBW was also predicted according to an empirical formula. Differences were analysed using Bland-Altman plots.

RESULTS: The mean TBW values obtained from the impedance measurement differed in the order of -2.21 (DIL) to 1.41 (DXA) in women and -2.01 (DIL) to 2.61 (DXA) in men, from the measured and derived values of total body water. Prediction of TBW gave values that were close to BIS, with a mean difference of -0.31 in male subjects and +0.51 in female subjects. Assessment of ECW revealed that the mean difference between dilution and impedance was less in women than in men (P<0.01).

CONCLUSION: The differences between all methods to assess fluid compartments are pronounced. To further investigate the use of the method in clinical practice for dynamic monitoring of rehydration in ileostomates with acute diarrhoea, repeated measurements together with comparison with weight fluid-balance charts are suggested.

SPONSORSHIP: The study was supported by grants from the Swedish Medical Research Council (17X-03117), Göteborgs Läkarsällskap and IB and A Lundbergs forskningsstiftelse.}, } @article {pmid12076930, year = {2002}, author = {Kawashima, M and Tamaki, Y and Nonaka, T and Higuchi, K and Kimura, M and Koida, T and Yanagita, Y and Sugihara, S}, title = {MR imaging of mucinous carcinoma of the breast.}, journal = {AJR. American journal of roentgenology}, volume = {179}, number = {1}, pages = {179-183}, doi = {10.2214/ajr.179.1.1790179}, pmid = {12076930}, issn = {0361-803X}, mesh = {Adenocarcinoma, Mucinous/*pathology/surgery ; Adult ; Aged ; Breast Neoplasms/*pathology/surgery ; Contrast Media ; Female ; Gadolinium DTPA ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Time Factors ; }, abstract = {OBJECTIVE: We examined retrospectively the MR imaging findings in eight patients with mucinous carcinoma of the breast to better describe the imaging characteristics of this disease.

CONCLUSION: The MR imaging findings in mucinous carcinomas include dynamic curves of the gradually enhancing type and a very high signal intensity on T2-weighted images compared with other histologic types of invasive ductal carcinoma. These findings appear to be useful for diagnosis.}, } @article {pmid12072425, year = {2002}, author = {Komori, T and Ishikawa, O and Ohigashi, H and Yamada, T and Sasaki, Y and Imaoka, S and Nakaizumi, A and Uehara, H and Tanaka, S and Mano, Y and Kasugai, T}, title = {Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation.}, journal = {Japanese journal of clinical oncology}, volume = {32}, number = {4}, pages = {146-151}, doi = {10.1093/jjco/hyf032}, pmid = {12072425}, issn = {0368-2811}, mesh = {Adenocarcinoma, Mucinous/*genetics/pathology ; Aged ; Base Sequence ; Carcinoma, Pancreatic Ductal/*genetics/pathology ; Carcinoma, Papillary/*genetics/pathology ; Female ; Genes, ras/*genetics ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pancreatectomy ; Pancreatic Neoplasms/*genetics/pathology/surgery ; *Point Mutation ; }, abstract = {Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.}, } @article {pmid12070597, year = {2002}, author = {Iwaya, K and Ogawa, H and Izumi, M and Kuroda, M and Mukai, K}, title = {Stromal expression of CD10 in invasive breast carcinoma: a new predictor of clinical outcome.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {440}, number = {6}, pages = {589-593}, doi = {10.1007/s00428-002-0639-4}, pmid = {12070597}, issn = {0945-6317}, mesh = {Adult ; *Biomarkers, Tumor ; Breast Neoplasms/*metabolism/*pathology ; Carcinoma, Ductal, Breast/*metabolism/*pathology ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neprilysin/*biosynthesis ; Prognosis ; Stromal Cells/metabolism/pathology ; }, abstract = {CD10 is a cell surface neutral endopeptidase that is not consistently expressed in the stromal cells of the normal breast. Expression of CD10 is sometimes observed in the stromal cells of invasive ductal carcinoma, but its clinical significance has never been studied. Immunohistochemical examination of CD10 was performed in 123 cases of breast cancer. The median follow-up period of all patients was 8.0 years, and univariate and multivariate analyses were performed to evaluate the prognostic significance of stromal CD10 expression. There was no staining in the stromal cells of 13 non-invasive ductal carcinomas or normal breast tissue. Of 110 invasive ductal carcinomas, 20 cases (18%) in which more than 10% of the stromal cells stained positive throughout the cancer tissue were judged "positive". The frequency of positive stromal staining was significantly higher in the cases with axillary lymph-node metastasis (P=0.038), but there were no correlations between stromal CD10 expression and age, tumor size, histologic grade, or clinical stage. The patients whose tumors contained CD10-positive stromal cells had a shorter metastasis-free interval (P=0.0008). Univariate analysis demonstrated that patients with lymph-node metastasis also had a significantly shorter metastasis-free interval (metastasis vs no metastasis; P=0.0318). In the multivariate analysis, only CD10 remained a significant predictor for time to recurrence (P=0.0059), and CD10 was the single significant prognostic factor for overall survival in the univariate analysis (P=0.0021). These results suggest that stromal expression of CD10 in breast cancer is an important novel prognostic factor.}, } @article {pmid12066205, year = {2002}, author = {Aoki, T and Nagakawa, Y and Tsuchida, A and Kasuya, K and Kitamura, K and Inoue, K and Ozawa, T and Koyanagi, Y and Itoi, T}, title = {Expression of cyclooxygenase-2 and vascular endothelial growth factor in pancreatic tumors.}, journal = {Oncology reports}, volume = {9}, number = {4}, pages = {761-765}, pmid = {12066205}, issn = {1021-335X}, mesh = {Adenocarcinoma/enzymology/pathology ; Adenocarcinoma, Mucinous/enzymology/pathology ; Adenoma/enzymology/pathology ; Carcinoma, Pancreatic Ductal/enzymology/pathology ; Cyclooxygenase 2 ; Endothelial Growth Factors/*metabolism ; Humans ; Immunoenzyme Techniques ; Intercellular Signaling Peptides and Proteins/*metabolism ; Isoenzymes/*metabolism ; Lymphatic Metastasis ; Lymphokines/*metabolism ; Membrane Proteins ; Neoplasm Invasiveness ; Pancreatic Neoplasms/*enzymology/pathology ; Papilloma, Intraductal/enzymology/pathology ; Prostaglandin-Endoperoxide Synthases/*metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.}, } @article {pmid12060456, year = {2002}, author = {Zehetleitner, G and Thiel, I and Petru, E}, title = {Long-term disease-free survival after breast cancer metastatic to the ovary.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {12}, number = {3}, pages = {317-318}, doi = {10.1046/j.1525-1438.2002.t01-2-01126.x}, pmid = {12060456}, issn = {1048-891X}, mesh = {Adult ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/radiotherapy/*secondary/surgery ; Disease-Free Survival ; Female ; Humans ; Laparotomy ; Mastectomy, Radical ; Ovarian Neoplasms/radiotherapy/*secondary/surgery ; Radiotherapy, Adjuvant ; Treatment Outcome ; }, abstract = {The prognosis of patients with breast cancer symptomatically metastatic to the ovary is almost uniformly poor. In this case report, we present a 33-year-old para-4 with a symptomatic metastasis to the ovary. Previously, a modified radical mastectomy with adjuvant radiotherapy had been performed for invasive ductal carcinoma of the left breast. Laparotomy showed a 13-cm tumor of the left ovary; frozen section histology showed malignancy consistent with the previous breast cancer. The patient received adjuvant combination chemotherapy. About 5 years later, a carcinoma of the right breast was treated with conservative surgery and adjuvant radiation and chemotherapy. After a further 4 years, a recurrence at the left chest wall was treated with radiation. At the last follow-up, more than 13 years after the first breast cancer and 12 years after the ovarian metastasis, the patient was alive and well without evidence of disease. Bilateral oophorectomy is a therapeutic option in premenopausal patients with localized or advanced breast cancer. Our patient experienced long-term disease-free survival following an isolated metastasis to one ovary. This represents the first report of long-term survival of such a patient in the literature.}, } @article {pmid12037031, year = {2002}, author = {Megha, T and Ferrari, F and Benvenuto, A and Bellan, C and Lalinga, AV and Lazzi, S and Bartolommei, S and Cevenini, G and Leoncini, L and Tosi, P}, title = {p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin.}, journal = {Journal of clinical pathology}, volume = {55}, number = {6}, pages = {461-466}, pmid = {12037031}, issn = {0021-9746}, mesh = {Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology ; Cell Division ; ErbB Receptors/metabolism ; Female ; *Genes, p53 ; Humans ; Keratins/metabolism ; Middle Aged ; Mitotic Index ; *Mutation ; Neoplasm Proteins/metabolism ; Neoplastic Stem Cells/pathology ; Phenotype ; Polymerase Chain Reaction/methods ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Vimentin/metabolism ; }, abstract = {AIM: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information.

METHODS: The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP).

RESULTS: Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression.

CONCLUSIONS: These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.}, } @article {pmid12034524, year = {2002}, author = {Ojopi, EP and Cavalli, LR and Cavalieri, LM and Squire, JA and Rogatto, SR}, title = {Comparative genomic hybridization analysis of benign and invasive male breast neoplasms.}, journal = {Cancer genetics and cytogenetics}, volume = {134}, number = {2}, pages = {123-126}, doi = {10.1016/s0165-4608(01)00613-6}, pmid = {12034524}, issn = {0165-4608}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms, Male/*genetics/*pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 11/genetics ; Chromosomes, Human, Pair 17/genetics ; Chromosomes, Human, Pair 4/genetics ; Chromosomes, Human, Pair 8/genetics ; Cytogenetic Analysis ; Humans ; Male ; Neoplasm Invasiveness/*genetics ; Nucleic Acid Hybridization ; }, abstract = {Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3 through pter, 11p14 through q12, and 17p11.2 through qter, and loss of 1q41 through qter and 4q33 through qter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2 through qter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer.}, } @article {pmid12033967, year = {2002}, author = {Al-Ahmadie, H and Hasselgren, PO and Yassin, R and Mutema, G}, title = {Colocalized granular cell tumor and infiltrating ductal carcinoma of the breast.}, journal = {Archives of pathology & laboratory medicine}, volume = {126}, number = {6}, pages = {731-733}, doi = {10.5858/2002-126-0731-CGCTAI}, pmid = {12033967}, issn = {0003-9985}, mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/chemistry/*pathology/therapy ; Combined Modality Therapy ; Female ; Granular Cell Tumor/chemistry/*pathology/therapy ; Humans ; Immunohistochemistry ; Keratins/analysis ; Mastectomy ; Middle Aged ; Neoplasms, Second Primary/chemistry/*pathology/therapy ; Radiotherapy ; Receptors, Estrogen/analysis ; }, abstract = {A 57-year-old woman presented with a 2-year history of a palpable mass in the upper inner quadrant of the right breast. A 1.1-cm, poorly circumscribed, firm tumor nodule was noted, consisting of 2 histologically distinct lesions in the same location, with some areas showing purely well-differentiated invasive ductal carcinoma and others composed of granular cell tumor. In 1 area, the 2 tumors collided and infiltrated each other. The invasive ductal carcinoma was admixed with ductal carcinoma in situ of solid and cribriform types. To our knowledge, this is the first case report demonstrating colocalization of these 2 neoplasms, which raises questions regarding causal relationship. We also review the literature on granular cell tumor of the breast.}, } @article {pmid12031704, year = {2002}, author = {Tiago, AD and Badenhorst, D and Skudicky, D and Woodiwiss, AJ and Candy, GP and Brooksbank, R and Sliwa, K and Sareli, P and Norton, GR}, title = {An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy.}, journal = {Cardiovascular research}, volume = {54}, number = {3}, pages = {584-589}, doi = {10.1016/s0008-6363(02)00281-x}, pmid = {12031704}, issn = {0008-6363}, mesh = {Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Angiotensinogen/genetics ; Cardiomyopathy, Dilated/*enzymology/pathology/*physiopathology ; Case-Control Studies ; Cytochrome P-450 CYP11B2/*genetics ; Digoxin/therapeutic use ; Diuretics/therapeutic use ; Echocardiography ; Enzyme Inhibitors/therapeutic use ; Female ; Furosemide/therapeutic use ; Heart Ventricles/pathology ; Humans ; Logistic Models ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/genetics ; *Polymorphism, Genetic ; Radionuclide Ventriculography ; *Stroke Volume ; }, abstract = {OBJECTIVE: To assess whether renin-angiotensin-aldosterone (RAA) system gene polymorphisms shown to be associated with alterations in the activity of the system, may predict cardiac function changes subsequent to initiating medical therapy in heart failure.

METHODS: The impact of RAA system genotypes on left ventricular ejection fraction (LVEF) following therapy to patients with idiopathic dilated cardiomyopathy (IDC) and class II-III heart failure was assessed. In 107 patients LVEF and LV dimensions were determined using radionuclide ventriculography and echocardiography prior to and subsequent to receiving furosemide, digoxin and angiotensin-converting enzyme (ACE) inhibitor therapy. Patients and controls were genotyped for variants of the ACE (insertion-deletion polymorphism), angiotensinogen (AGT; M235T polymorphism) and the aldosterone synthase (CYP11B2, C-344T polymorphism) genes.

RESULTS: RAA system genotypes were not significantly associated with LVEF prior to initiating medical therapy. However, the CYP11B2 gene variant (P=0.0064 on covariate analysis [adjusted for multiple genotyping] with a 1-2% chance of false positive data), but neither the ACE, nor the AGT variants, predicted improvement in LV ejection fraction in patients on medical therapy.

CONCLUSION: A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.}, } @article {pmid12029439, year = {2002}, author = {Tsuura, Y and Suzuki, T and Honma, K and Sano, M}, title = {Expression of c-kit protein in proliferative lesions of human breast: sexual difference and close association with phosphotyrosine status.}, journal = {Journal of cancer research and clinical oncology}, volume = {128}, number = {5}, pages = {239-246}, doi = {10.1007/s00432-002-0329-2}, pmid = {12029439}, issn = {0171-5216}, mesh = {Breast/metabolism/pathology ; Breast Neoplasms/*genetics/metabolism/physiopathology ; Breast Neoplasms, Male/*genetics/metabolism/physiopathology ; Female ; Fibrocystic Breast Disease/*genetics/metabolism/physiopathology ; Humans ; Hyperplasia ; Male ; Proto-Oncogene Proteins c-kit/biosynthesis/*genetics ; Sex Factors ; }, abstract = {PURPOSE: The c-kit gene which codes transmembrane tyrosine kinase receptor protein plays an important role in several types of normal and/or neoplastic human tissues. We examined the expression patterns of c-kit protein in proliferative lesions of human breast tissues in both sexes.

METHODS: The localization of c-kit protein was examined immunohistochemically in human breast, consisting of 366 normal tissue, 156 benign lesions (fibroadenoma, fibrocystic change, intraductal papilloma, benign phyllodes tumor, and gynecomastia), 13 borderline diseases (atypical ductal hyperplasia, atypical lobular hyperplasia, and borderline malignant phyllodes tumor), and 197 malignant lesions (non-invasive and/or invasive ductal carcinoma and malignant phyllodes tumor).

RESULTS: In normal tissues and benign proliferative lesions, c-kit product was consistently detected on epithelial cell membranes and/or cytoplasms regardless of gender difference. In contrast, we failed to find c-kit product in female borderline epithelial lesions, including atypical lobular hyperplasia, or in female malignant lesions, except for two carcinomas. In situ hybridization analysis of c-kit mRNA in female tissues gave results comparable to those obtained by immunohistochemistry. On the other hand, c-kit product was consistently detected in male benign and malignant proliferative lesions. Apart from the female breast carcinomas which lacked c-kit, c-kit expression was almost always accompanied by positivity for phosphotyrosine in the breast tissues examined, suggesting possible phosphorylation of tyrosine residues of the c-kit receptor protein.

CONCLUSIONS: Loss of c-kit product was related to malignant transformation in female breast, but not in the case of male breast. We suggest that the oncogenesis pathway of breast epithelium is different between males and females in terms of c-kit expression.}, } @article {pmid12026054, year = {2002}, author = {Rajesh, L and Dey, P and Joshi, K}, title = {Automated image morphometry of lobular breast carcinoma.}, journal = {Analytical and quantitative cytology and histology}, volume = {24}, number = {2}, pages = {81-84}, pmid = {12026054}, mesh = {Biopsy, Needle ; Breast/pathology ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/*pathology ; Cell Nucleus/pathology ; Diagnosis, Differential ; Female ; Fibroadenoma/pathology ; Fibrocystic Breast Disease/pathology ; Humans ; Hyperplasia/pathology ; Image Cytometry/*methods ; *Image Processing, Computer-Assisted ; }, abstract = {OBJECTIVE: To analyze the role of automated image morphometry (AIM) in distinguishing infiltrating lobular carcinoma (ILC) of the breast from benign, borderline and infiltrating ductal carcinoma (IDC).

STUDY DESIGN: Only histopathologically proven lobular carcinoma, ductal carcinoma, borderline lesions and benign breast lesions were selected for the study. There were 19 cases of ILC and 30 cases of IDC, 20 cases of benign lesions (fibroadenoma, 18; fibrocystic disease, 1; and fibroadenosis, 1); 10 cases were borderline lesions (mild epithelial hyperplasia, 3; moderate epithelial hyperplasia, 2; florid epithelial hyperplasia 4; intraductal papillary carcinoma, 1). In all cases hematoxylin and eosin-stained slides were used for AIM. At least 100 cells from each case were subjected to analysis randomly with an image cytometer with Leica Quantimet 600 software (Cambridge, England). Nuclear area, diameter, perimeter, convex perimeter, convex area and roundness were measured in each case with random, unbiased selection of cells and 40 x objectives (one pixel = 0.46 microm). AIM data on the cases were analyzed in relation to final cytologic diagnosis.

RESULTS: All the nuclear morphometric features of ILC were much lower than those of IDC and borderline lesions, whereas nuclear morphometric data on ILC were only marginally more than those on benign cases. ANOVA showed that mophometric data were significant (P < .05) in all the variables between ILC and IDC. However, there was no significant difference between ILC, and borderline and benign cases.

CONCLUSION: Image morphometry may be useful in distinguishing ILC from IDC on cytologic smears. However, morphometric data may not be helpful in distinguishing benign and borderline lesions from ILC.}, } @article {pmid12016392, year = {2002}, author = {Matsuo, K and Fukutomi, T and Akashi-Tanaka, S and Hasegawa, T and Tsuda, H}, title = {Histological grade, p53, HER2 and hormone receptor status of synchronous bilateral breast carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {9}, number = {2}, pages = {127-133}, doi = {10.1007/BF02967577}, pmid = {12016392}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma/*pathology ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Squamous Cell/pathology ; Chi-Square Distribution ; Female ; *Genes, erbB-2 ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Staging ; Probability ; Prognosis ; Receptors, Estrogen/analysis/*biosynthesis ; Receptors, Progesterone/analysis/*biosynthesis ; Retrospective Studies ; Sensitivity and Specificity ; Tumor Suppressor Protein p53/analysis/*biosynthesis ; }, abstract = {BACKGROUND AND OBJECTIVES: Histological grade and tumor biology remain important predictors of the clinical behavior of breast carcinomas. We analyzed the clinicopathological characteristics and tumor biology with regard to histological grade (HG), p53, HER2 and hormone receptor status to address this question.

PATIENTS AND METHODS: A consecutive series of 74 female synchronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital were the primary source of these retrospective data. Clinicopathological background factors, histological grade and immunohistochemical staining for p53, HER2 and hormone receptor status, were analyzed.

RESULTS: Of 148 synchronous bilateral tumors, 102 were invasive ductal carcinoma (IDC). The others included 24 pure or predominant ductal carcinoma in situ (DCIS), 5 spindle cell carcinomas, 16 invasive lobular carcinomas and 1 squamous cell carcinoma. 128 cases (128/148: 89%) were HG 1 (72/148: 49%) or HG 2 (56/148: 38%). The positivity rates for p53, HER2, estrogen receptor (ER) and progesterone receptor (PR) were 9%(14/148), 18%(26/148), 64%(95/148) and 64%(95/148), respectively.

CONCLUSION: Our findings indicate that synchronous bilateral breast carcinomas showed a higher frequency of invasive lobular carcinoma, lower HG and higher rate of hormone receptor positivity than unilateral breast carcinomas.}, } @article {pmid12021928, year = {2002}, author = {Röcken, C and Kronsbein, H and Sletten, K and Roessner, A and Bässler, R}, title = {Amyloidosis of the breast.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {440}, number = {5}, pages = {527-535}, doi = {10.1007/s00428-001-0555-z}, pmid = {12021928}, issn = {0945-6317}, mesh = {Aged ; Aged, 80 and over ; Amino Acid Sequence ; Amyloidosis/complications/*diagnosis/pathology ; Biopsy ; Breast Diseases/complications/*diagnosis/pathology ; Breast Neoplasms/complications/diagnosis/pathology ; Calcinosis/diagnosis/pathology ; Carcinoma, Ductal, Breast/complications/pathology ; Carcinoma, Lobular/complications/diagnosis/pathology ; Female ; Humans ; Immunoglobulin kappa-Chains/analysis/chemistry ; Lymphatic Metastasis ; Microscopy, Electron ; Middle Aged ; Peptide Fragments/chemistry ; }, abstract = {We report on three cases of amyloidosis of the breast, two of which coincided with breast cancer. Patient no. 1, a 60-year-old woman, presented with two mass lesions measuring 2 cm in diameter, one in each breast. Histologically, a tubulo-lobular carcinoma was found in the left breast accompanied by vascular, interstitial, and periductal amyloid deposits; the lesion in the right breast consisted of amyloid deposits only. Patient no. 2, an 86-year-old woman, presented with an ulcerated breast tumor measuring 5 cm in diameter on the left side. A poorly differentiated invasive ductal carcinoma was found in the mastectomy specimen, and it coincided with interstitial and vascular amyloid deposits. In both patients, tumor cells had invaded the amyloid deposits. Patient no. 3, a 73-year-old woman, presented with a mass measuring 5 x 3 x 3 cm in her left breast. Fibrocystic changes, as well as interstitial and periductal amyloid deposits, were found histologically. In each case electron microscopy showed rigid, non-branching fibrils of indefinite length and measuring 10-12 nm in diameter; these were consistent with amyloid fibrils. Clinical data, immunohistochemistry, and/or amino acid sequencing of the fibril proteins extracted from formalin-fixed and paraffin-embedded tissue specimens provided evidence that the amyloid deposits were of immunoglobulin light chain origin in all three cases. A review of the literature revealed that kappa-light chain has been described more frequently than lambda-light chain in the breast and that there are no specific clinical or radiological symptoms of amyloidosis affecting the breast; a diagnosis can be achieved only by histology.}, } @article {pmid12020967, year = {2002}, author = {Kouwenhoven, M and Ozenci, V and Tjernlund, A and Pashenkov, M and Homman, M and Press, R and Link, H}, title = {Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis.}, journal = {Journal of neuroimmunology}, volume = {126}, number = {1-2}, pages = {161-171}, doi = {10.1016/s0165-5728(02)00054-1}, pmid = {12020967}, issn = {0165-5728}, mesh = {Adult ; Cell Movement/immunology ; Dendritic Cells/cytology/*enzymology/metabolism ; Female ; Flow Cytometry ; Gene Expression Regulation, Enzymologic/immunology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Matrix Metalloproteinase 1/genetics/metabolism ; Matrix Metalloproteinase 2/genetics/metabolism ; Matrix Metalloproteinase 3/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Metalloendopeptidases/*genetics/metabolism ; Middle Aged ; Monocytes/*cytology ; Multiple Sclerosis/immunology/metabolism/*physiopathology ; RNA, Messenger/analysis ; Tissue Inhibitor of Metalloproteinase-1/*genetics/metabolism ; Tissue Inhibitor of Metalloproteinase-2/*genetics/metabolism ; }, abstract = {Dendritic cells (DC) are antigen-presenting cells (APC) that most efficiently initiate and control immune responses. Migration processes of blood DC are crucial to exert their professional antigen-presenting functions. Matrix-degrading metalloproteinases (MMP) are proteolytic enzymes, which are considered to be key enzymes in extracellular matrix (ECM) turnover and mediators of cell migration. Tissue inhibitors of metalloproteinases (TIMP) are important regulators of MMP activity. Here we investigate whether blood monocyte-derived immature DC (iDC) and mature DC (mDC) express, produce and secrete functionally active MMP-1, -2, -3 and -9 and their inhibitors TIMP-1 and -2, and examine their involvement in multiple sclerosis (MS). On mRNA level, we observed high numbers of MMP-2 and TIMP-2 mRNA expressing iDC in MS. On protein level, high percentages of MMP-1, -2 and -9 expressing iDC by flow cytometry, and high MMP-1 secretion by Western blot together with high MMP-2 and -9 activities in iDC supernatants as studied with zymography were observed. Similarly, MS is associated with high percentages of MMP-2 and -3 and of TIMP-1 expressing mDC by flow cytometry together with high MMP-3 secretion and high MMP-9 activity in culture supernatants. Spontaneous migratory capacity of both iDC and mDC over ECM-coated filters was higher in MS compared to healthy controls (HC). In conclusion, blood monocyte-derived iDC and mDC express, produce and secrete several MMP and TIMP. Alterations in these molecules as observed in MS may be functionally important for DC functioning.}, } @article {pmid12015744, year = {2002}, author = {Nakamura, A and Horinouchi, M and Goto, M and Nagata, K and Sakoda, K and Takao, S and Imai, K and Kim, YS and Sato, E and Yonezawa, S}, title = {New classification of pancreatic intraductal papillary-mucinous tumour by mucin expression: its relationship with potential for malignancy.}, journal = {The Journal of pathology}, volume = {197}, number = {2}, pages = {201-210}, doi = {10.1002/path.1109}, pmid = {12015744}, issn = {0022-3417}, support = {CA24321/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma, Mucinous/*classification/metabolism/pathology ; Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Carcinoma, Pancreatic Ductal/*classification/metabolism/pathology ; Carcinoma, Papillary/*classification/metabolism/pathology ; Cell Division ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Mucin-2 ; Mucins/*metabolism ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Pancreatic Neoplasms/*classification/metabolism/pathology ; Treatment Outcome ; }, abstract = {In previous studies of the expression of MUC1 (membrane-bound type mucin) and MUC2 (intestinal type secretory mucin) in pancreatic tumours, invasive ductal carcinoma (IDC) usually showed MUC1+ and MUC2- expression, whereas intraductal papillary-mucinous tumour (IPMT) showed MUC1- and MUC2+ expression. Recently, however, many IPMTs have been collected, a considerable number of which have shown MUC1- and MUC2- expression. In the present study, the clinicopathological features were examined of 18 IPMTs with MUC2+ and 32 IPMTs with MUC2-, and their potential for malignancy was compared. Most of the IPMTs with MUC2+ were composed of dark columnar cells, whereas most of the IPMTs with MUC2- were composed of clear columnar cells. The incidence of carcinomatous change and invasive proliferation of the carcinoma in the MUC2+ tumours was significantly higher than in the MUC2- tumours. The clinical outcome for the patients with IPMT showing the MUC2+ pattern tended to be worse than for those with IPMT showing the MUC2- pattern, although the overall outcome for the two types of IPMT was significantly better than for those with IDC. Because of the differences in mucin expression pattern, morphological appearance and potential for malignancy between the two types of IPMT, we believe that they belong to different neoplastic lineages and that it may be reasonable to classify them as different entities, although the WHO classification contains a single clinicopathological entity of IPMT forming an adenoma-carcinoma sequence. In conclusion, our classification of IPMTs by MUC2 expression pattern may be of value in the better assessment of the biological behaviour of IPMTs and their potential for malignancy.}, } @article {pmid12014222, year = {2002}, author = {Patla, A and Rudnicka-Sosin, L and Pawlega, J and Stachura, J}, title = {Prognostic significance of selected immunohistochemical parameters in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {53}, number = {1}, pages = {25-27}, pmid = {12014222}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis/metabolism ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma in Situ/*metabolism/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/mortality/secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Second Primary/metabolism/pathology ; Precancerous Conditions/*metabolism/pathology ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; }, abstract = {The purpose of the present study was to carry out multivariate analysis of the effect of the expression of estrogen and progesterone receptors, p53, proliferative antigen (Ki67) and c-erbB-2 on 5-year survival in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ. Material for study consisted of tissue specimens obtained from 48 patients undergoing modified Patey's mastectomy between 1991 and 1998. Univariate analysis revealed that the variables significantly affecting survival were tumour size on gross examination and the level of estrogen and progesterone receptors in the cells of invasive ductal carcinoma of the breast (for the level of significance p = 0.05). The Cox regression model revealed that the only independent variable having a significant effect on survival was the level of estrogen receptors in invasive cancer cells.}, } @article {pmid12011255, year = {2002}, author = {Hasebe, T and Sasaki, S and Imoto, S and Mukai, K and Yokose, T and Ochiai, A}, title = {Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast: a prospective observational study.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {15}, number = {5}, pages = {502-516}, doi = {10.1038/modpathol.3880555}, pmid = {12011255}, issn = {0893-3952}, mesh = {Adult ; Aged ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Disease-Free Survival ; Female ; Fibrosis ; Follow-Up Studies ; Humans ; Lymph Nodes/pathology ; Middle Aged ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; }, abstract = {We have already reported invasive ductal carcinomas (IDCs) with fibrotic focus (FF) to be associated with significantly poorer survival than IDCs without FF. The purpose of this study was to prospectively investigate the effect of the presence of FF on the outcomes of 439 patients with IDCs to confirm the prognostic significance of FF, by the multivariate analysis, employing the Cox proportional hazard regression model, as compared with well-known clinicopathological parameters. We also precisely evaluated the prognostic significance of FF from the viewpoint of FF characteristics. The present study demonstrated that the presence of FF is a very useful parameter predicting tumor recurrence (TR), as well as initial distant organ metastasis (IDOM), in lymph node-negative IDCs (P =.024 and P =.026) and in IDCs positive for either or both estrogen receptor (ER) or progesterone receptor (PR) (P =.007 and P =.015), respectively. In addition, FF of >8 mm in diameter was found to be an independent prognostic parameter for TR and IDOM in lymph node-negative patients and patients with IDC positive for either or both ER or PR (P =.005 and P =.018). We conclude that the presence of FF is a very important histologic prognostic parameter for patients with IDCs of the breast.}, } @article {pmid12006697, year = {2002}, author = {Kishimoto, R and Watanabe, Y and Shimizu, M}, title = {Best cases from the AFIP: invasive ductal carcinoma with osteoclast-like giant cells.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {22}, number = {3}, pages = {691-695}, doi = {10.1148/radiographics.22.3.g02ma13691}, pmid = {12006697}, issn = {0271-5333}, mesh = {Breast/*pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Contrast Media ; Female ; Gadolinium DTPA ; Giant Cells/pathology ; Humans ; *Magnetic Resonance Imaging ; Middle Aged ; Osteoclasts ; }, } @article {pmid12004646, year = {2002}, author = {Chlebovská, K and Chlebovskỳ, O and Ahlers, I and Ahlersová, E and Bacenková, D}, title = {Effect of K, MG aspartate on some biological parameters of aging rats.}, journal = {Archives italiennes de biologie}, volume = {140}, number = {2}, pages = {91-100}, pmid = {12004646}, issn = {0003-9829}, mesh = {Aging/*drug effects/metabolism/radiation effects ; Animals ; Aspartic Acid/*pharmacology ; Blood Proteins/*drug effects/metabolism/radiation effects ; Complement C3/drug effects/metabolism/radiation effects ; Gamma Rays/adverse effects ; Haptoglobins/drug effects/metabolism/radiation effects ; Hemopexin/drug effects/metabolism/radiation effects ; Immunity, Innate/drug effects/immunology/radiation effects ; Male ; Neutrophils/drug effects/metabolism/radiation effects ; Phagocytosis/drug effects/immunology/radiation effects ; Rats ; Rats, Wistar ; Serum Albumin/drug effects/metabolism/radiation effects ; Survival Rate ; Transferrin/drug effects/metabolism/radiation effects ; }, abstract = {The effect of K and Mg salts of aspartic acid (Cardilan) on the serum concentration of selected proteins and phagocytic activity in aging male Wistar rats was investigated. Cardilan was administered in tap water for 7 days a month for 3 months before the last observed interval (12, 18 and 24 month). In a part of animals, the aging process was accelerated by sublethally gamma-irradiation. The administration of Cardilan slowed down the changes in the concentration of prealbumin, albumin, haptoglobin, haemopexin, C3 complement in non-irradiated rats (DC). This effect was extended to the changes in transferrin level in irradiated rats (IDC). The phagocytic activity in both DC, IDC rats was lower compared with controls drinking water (DW, IDW), but not significantly. The effect of Cardilan administration appears to be the greatest in 24-month-old rats, when the treated animals survived better by 25% in IDC group and by 26% better in DC rats, compared with those of the same age controls. Potassium and magnesium salts of aspartates are suitable compounds for life prolongation in the experimental conditions.}, } @article {pmid12003264, year = {2002}, author = {Hara, J and Plymale, DR and Shepard, DL and Hara, H and Garry, RF and Yoshihara, T and Zenner, HP and Bolton, M and Kalkeri, R and Fermin, CD}, title = {Avian dark cells.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {259}, number = {3}, pages = {121-141}, doi = {10.1007/s004050100407}, pmid = {12003264}, issn = {0937-4477}, support = {A1-34754//PHS HHS/United States ; }, mesh = {Animals ; Chickens ; Ear, Inner/*cytology/*metabolism ; Hair Cells, Auditory/metabolism/ultrastructure ; Homeostasis ; Hydrogen-Ion Concentration ; Microscopy, Fluorescence ; Potassium Channels/metabolism ; Sodium Channels/metabolism ; Stria Vascularis/*metabolism/*ultrastructure ; }, abstract = {Dark cells (DCs) of mammalian and non-mammalian species help to maintain the homeostasis of the inner ear fluids in vivo. Although the avian cochlea is straight and the mammalian cochlea is coiled, no significant difference in the morphology and/or function of mammalian and avian DCs has been reported. The mammalian equivalent of avian DCs are marginal cells and are located in the stria vascularis along a bony sheet. Avian DCs hang free from the tegmentum vasculosum (TV) of the avian lagena between the perilymph and endolymph. Frame averaging was used to image the fluorescence emitted by several fluorochromes applied to freshly isolated dark cells (iDCs) from chickens (Gallus domesticus) inner ears. The viability of iDCs was monitored via trypan blue exclusion at each isolation step. Sodium Green, BCECF-AM, Rhodamine 123 and 9-anthroyl ouabain molecules were used to test iDC function. These fluorochromes label iDCs ionic transmembrane trafficking function, membrane electrogenic potentials and Na+/K+ ATPase pump's activity. Na+/K+ ATPase pump sites, were also evaluated by the p-nitrophenyl phosphatase reaction. These results suggest that iDCs remain viable for several hours after isolation without special culturing requirements and that the number and functional activity of Na+/K+ ATPase pumps in the iDCs were indistinguishable from in vivo DCs. Primary cultures of freshly iDCs were successfully maintained for 28 days in plastic dishes with RPMI 1640 culture medium. The preparation of iDCs overcomes the difficulty of DCs accessability in vivo and the unavoidable contamination that rupturing the inner ear microenvironments induces.}, } @article {pmid12001424, year = {2002}, author = {Velasco-Murillo, V and Ojeda-Mijares, RI and Navarrete-Hernández, E and Pozos-Cavanzo, JL and Camacho-Rodríquez, Mde L}, title = {[Training experience in climacteric and menopause among physicians of the IMSS].}, journal = {Gaceta medica de Mexico}, volume = {138}, number = {2}, pages = {145-148}, pmid = {12001424}, issn = {0016-3813}, mesh = {*Climacteric ; *Clinical Competence ; Family Practice ; Female ; Gynecology ; Humans ; *Menopause ; Mexico ; Obstetrics ; Prospective Studies ; Social Security ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: To analyze the level of knowledge concerning climateric and menopause among family physicians and gynecologists and obstetricians of the Instituto Mexicano del Seguro Social (IMSS), after a training process in institutional technical guidelines and in educational content for population. We also analyze possible changes in frequency of medical attention for climateric and menopause in the first level of medical care.

MATERIAL AND METHODS: Prospective and descriptive study on 1) results of the knowledge evaluation by means of 23 questions with multiple answers, and 2) analysis of rates of medical care for menopausal and perimenopausal disturbances (N95 code, X Revision, IDC) from 1995 to 2000.

RESULTS: The percentage of correct answers prior to training was 62.2 for family physicians and 65.9 for gynecologists and obstetricians; after training, 79.3 and 81.4, respectively. Both groups had on increase in knowledge levels (p < 0.001) but there were no differences among them. An increase was registered in medical care rates for menopausal and perimenopausal disturbances in the group from 45 to 64 years of age in the period from 1995 to 2000.

CONCLUSIONS: All physicians had on increase in knowledge on climateric and menopause issues but without differences among them, probably because the care of this health problem is referred to specialized services and as well as to more attention on other more frequent problems in women's health. In addition, we did not find changes yet in the rates of medical attentions attributable to training and information to population.}, } @article {pmid12001109, year = {2002}, author = {de Mascarel, I and MacGrogan, G and Mathoulin-Pélissier, S and Soubeyran, I and Picot, V and Coindre, JM}, title = {Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas.}, journal = {Cancer}, volume = {94}, number = {8}, pages = {2134-2142}, doi = {10.1002/cncr.10451}, pmid = {12001109}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma in Situ/mortality/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery/therapy ; Female ; Humans ; Lymph Nodes/*pathology ; Microtomy ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Radiotherapy ; Survival Rate ; }, abstract = {BACKGROUND: The significance of microinvasion is still debated and clinical management is controversial. The authors defined ductal carcinoma in situ with microinvasion (DCIS-MI) as DCIS with infiltration of the periductal stroma by a few tumor cells, singly (type 1) or in clusters (type 2). With this definition, the authors attempted to evaluate the clinical significance of microinvasion.

METHODS: The authors compared the clinical, pathologic features, and survival (median follow-up, 7.3 years) of 1248 patients with, respectively, DCIS (722 patients), DCIS-MI with microinvasion type 1 and type 2 (243 patients), and invasive ductal carcinoma in situ with a predominant DCIS component greater than or equal to 80% of the tumor (IDC-DCIS, 283 patients).

RESULTS: Microinvasion was associated with DCIS histologic type, grade, and extent (respectively, P < 10(-8), P < 10(-3), P < 10(-4)). Axillary lymph node metastases were observed in a few patients with DCIS and DCIS-MI type 1 (respectively, 1.4% and none), in 10.1% with DCIS-MI type 2 and in 27.6% with IDC-DCIS. Metastasis free and overall survival probabilities were significantly different between three groups in the following order from best to worst prognosis: 1) the group comprising DCIS and DCIS-MI type 1, 2) the DCIS-MI type 2 group, and 3) the IDC-DCIS group.

CONCLUSIONS: The authors' results suggest there are two types of DCIS-MI: 1) type 1 that behaves like DCIS and should be managed as such; 2) type 2 that is less pejorative than IDC-DCIS but is more so than type 1.}, } @article {pmid11994759, year = {2002}, author = {Park, SH and Kim, H and Song, BJ}, title = {Down regulation of bcl2 expression in invasive ductal carcinomas is both estrogen- and progesterone-receptor dependent and associated with poor prognostic factors.}, journal = {Pathology oncology research : POR}, volume = {8}, number = {1}, pages = {26-30}, pmid = {11994759}, issn = {1219-4956}, mesh = {Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; *Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*biosynthesis/genetics ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {In normal breast, Bcl2 is expressed in the non-pregnant and non-involuting mammary epithelium. The exact mechanism and the effect of the down regulation of the Bcl2 expression on breast cancer cells are not clearly defined. We compared down regulation as well as the persistent expression of Bcl2 with ER, PR, p53, and c-erb-B2 overexpression and clinicopathologic variables, and tumor stage in 11 cases of ductal carcinomas in situ (DCIS) and 44 cases of invasive ductal carcinomas (IDC) of Korean women by immunohistochemical studies. Bcl2 down regulation was found in 39% of IDC and in 18% of DCIS cases. In IDC, while persistent Bcl2 expression was displayed in 95% and 78.9% of ER and PR immunoreactive ones and 71.9 % of c-erb-B2 immunonegative ones. Seventeen cases of Bcl2 down regulated IDC had a significant correlation with ER negativity (94.1%), PR negativity, (76.5%), and high nuclear (61.1% is grade III) and histological grade (76% is grade III). However, in DCIS, no significant correlation between the Bcl2 expression and various parameters were obtained, probably due to small sample size. In conclusion, the Bcl2 expression was both ER and PR dependent and down regulation of Bcl2 in IDC was significantly correlated with poor prognostic factors.}, } @article {pmid11991512, year = {2002}, author = {Okamo, H and Miura, K and Yamane, T and Fujii, H and Matsumoto, Y}, title = {Invasive ductal carcinoma of the breast associated with Poland's syndrome: report of a case.}, journal = {Surgery today}, volume = {32}, number = {3}, pages = {257-260}, doi = {10.1007/s005950200030}, pmid = {11991512}, issn = {0941-1291}, mesh = {Arm/abnormalities ; Breast Neoplasms/*complications/surgery ; Carcinoma, Ductal, Breast/*complications/surgery ; Female ; Humans ; Lymph Node Excision ; Mastectomy, Segmental ; Middle Aged ; Pectoralis Muscles/abnormalities/diagnostic imaging ; Poland Syndrome/*complications ; Tomography, X-Ray Computed ; }, abstract = {We report herein a rare case of invasive ductal carcinoma of the breast associated with Poland's syndrome. The patient was a 59-year-old woman who was referred to our department after a nodule had been found in the upper outer portion of the left breast by a breast cancer screening program. On physical examination, marked hypoplasia of the right breast and upper limb was noted. Preoperative computed tomography also revealed a defect in the right pectoralis muscles. A quadrantectomy of the left breast with lymphadenectomy was subsequently performed and pathological examination of the resected specimen showed invasive ductal carcinoma. Her medical history revealed that her mother had attempted to abort the pregnancy around the fifth week of her gestation. The present case suggests that such an event during gestational development may be associated with congenital anomalies predisposing to malignant disorders.}, } @article {pmid11989854, year = {2002}, author = {Eyden, B and Banerjee, SS and Nesland, JM}, title = {Amphicrine carcinoma of breast with giant granules: an immunohistochemical, histochemical and ultrastructural study.}, journal = {Journal of submicroscopic cytology and pathology}, volume = {34}, number = {1}, pages = {27-36}, pmid = {11989854}, issn = {1122-9497}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*ultrastructure ; Carcinoma, Ductal, Breast/metabolism/*ultrastructure ; Carcinoma, Neuroendocrine/metabolism/*ultrastructure ; Female ; Humans ; Immunohistochemistry ; }, abstract = {A moderately differentiated grade 2 invasive ductal carcinoma was diagnosed in the right breast of an 81-year-old woman. The uniform nuclear profiles and moderately abundant granular cytoplasm suggested a neuroendocrine tumour and a Grimelius stain was positive. Neurone specific enolase, synaptophysin and somatostatin stained positively, and casein was interpreted as positive although with some background staining. By electron microscopy, tumour cells possessed desmosomes, tonofibrils, intercellular lumina, lamina and dense granules. Rounded dense granules 160-480 nm in diameter resembled neuroendocrine granules. They were found in both luminal and basal areas. Fewer and much larger ('giant') granules had a rounded profile and were up to 5 microm across. The smaller cytoplasmic granules were mostly Grimelius-positive while giant granules were negative. The smaller granules were also uranaffin-positive, but no uranaffin-positive cytoplasmic giant granules were encountered. Both small and giant granules were observed in lumina, and here both were uranaffin-positive. Intraluminal giant granules had a substructure of small pale lipid-like lacunae, and some had irregular profiles. The exceptional size of these exocrine granules is emphasised, and the nature of both the small and giant granules discussed in this amphicrine carcinoma.}, } @article {pmid11988771, year = {2002}, author = {Campbell, ID}, title = {Timeline: the march of structural biology.}, journal = {Nature reviews. Molecular cell biology}, volume = {3}, number = {5}, pages = {377-381}, doi = {10.1038/nrm800}, pmid = {11988771}, issn = {1471-0072}, mesh = {History, 20th Century ; History, 21st Century ; Molecular Biology/*history/trends ; *Molecular Structure ; }, abstract = {One hundred years ago, we knew very little about biological macromolecules and had no tools available to study their structure. Structural biology is now a mature science. New structures are being solved at an ever-increasing rate and there are important new initiatives to determine all the protein folds that are used by biological systems (structural genomics). This article traces some of the key developments in the field.}, } @article {pmid11988637, year = {2002}, author = {Casademont, J and Miró, O}, title = {Electron transport chain defects in heart failure.}, journal = {Heart failure reviews}, volume = {7}, number = {2}, pages = {131-139}, pmid = {11988637}, issn = {1382-4147}, mesh = {DNA, Mitochondrial/genetics/metabolism ; Energy Metabolism/genetics/physiology ; Heart Failure/*etiology/*metabolism/physiopathology ; Humans ; Mitochondria, Heart/genetics/metabolism ; Mitochondrial Diseases/*etiology/*metabolism/physiopathology ; Myocardial Contraction/genetics/physiology ; }, abstract = {In recent years, the possibility that disorders of cardiac metabolism play a role in the mechanisms that lead to ventricular dilatation and dysfunction in heart failure has attracted much attention. Electron transport chain is constituted by a series of multimeric protein complexes, located in the inner mitochondrial membranes, whose genes are distributed over both nuclear and mitochondrial DNA. Its normal function is essential to provide the energy for cardiac function. Many studies have described abnormalities in mitochondrial DNA genes encoding for electron transport chain (ETC) in dilated cardiomyopathies. In some cases, heart failure is one more or less relevant symptom among other multisystem manifestations characteristic of mitochondrial encephalomyopathies, being heart failure imputable to a primary mitochondrial disease. In the case of idiopathic dilated cardiomyopathies (IDC), many mitochondrial abnormalities have also been described using hystological, biochemical or molecular studies. The importance of such findings is under debate. The great variability in the mitochondrial abnormalities described has prompted the proposal that mitochondrial dysfunction could be a secondary phenomenon in IDC, and not a primary one. Among other possible explanations for such findings, the presence of an increased oxidative damage due to a free radical excess has been postulated. In this setting, the dysfunction of ETC could be a consequence, but also a cause of the presence of an increased free radical damage. Independently of its origin, ETC dysfunction may contribute to the persistence and worsening of heart failure. If this hypothesis, still to be proven, was certain, the modulation of cardiac metabolism could be an interesting approach to treat IDC. The precise mechanisms that lead to ventricular dilatation and dysfunction in heart failure are still nowadays poorly understood. Circumstances such as cytotoxic insults, viral infections, immune abnormalities, contractile protein defects, ischemic factors and familial conditions have been thoroughly investigated [1]. It is possible that several mechanisms combine to produce the clinical syndrome of heart failure. In recent years the possibility that disorders of energy metabolism, either isolated or in combination with the other aforementioned factors, may play a role in the development of heart failure in susceptible patients has attracted much attention. The present paper reviews the current knowledge on mitochondrial function in the failing myocardium. We restrain our discussion to heart failure where an impaired inotropic state leads to a weakened systolic contraction (i.e. the so-called systolic heart failure). Idiopathic dilated cardiomyopathy (IDC) is the prototype of the conditions under discussion. Other circumstances where a defect in myocardial contraction is due to a chronic excessive work load (i.e., hypertension, valvular or congenital heart diseases), and states in which the principal abnormality involves impaired relaxation of the ventricle (i.e. diastolic heart failure), as well as mitochondrial defects outside the electron transport chain (i.e., defects in Krebs cycle or beta-oxidation of fatty acids) are only approached circumstantially.}, } @article {pmid11988198, year = {2002}, author = {Rankovic, V and Karha, J and Passman, R and Kadish, AH and Goldberger, JJ}, title = {Predictors of appropriate implantable cardioverter-defibrillator therapy in patients with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {89}, number = {9}, pages = {1072-1076}, doi = {10.1016/s0002-9149(02)02278-6}, pmid = {11988198}, issn = {0002-9149}, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Cardiomyopathy, Dilated/*therapy ; *Defibrillators, Implantable ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Patient Selection ; Proportional Hazards Models ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {Evaluating predictors of appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with idiopathic dilated cardiomyopathy (IDC) may be helpful in developing risk stratification strategies for these patients. Fifty-four patients with IDC underwent ICD implantation and were followed up. Twenty-three patients (42%) had a class I indication for ICD implantation; the remaining patients underwent implantation for multiple risk factors for sudden death including left ventricular dysfunction, nonsustained ventricular tachycardia, syncope, or positive electrophysiologic study results. Clinical, electrocardiographic, and electrophysiologic data were collected. Appropriate ICD therapy was defined as an antitachycardia pacing therapy or shock for tachyarrhythmia determined to be either ventricular tachycardia or ventricular fibrillation. Appropriate ICD therapy was observed in 23 patients (42%). There was a significant difference in use of beta-blocker therapy between patients who did and did not have appropriate ICD therapy (p <0.0003). Cox regression analysis identified the following univariate predictors (p <0.1): class I indication (p <0.005) and lack of use of beta-blocker therapy (p <0.0007). In multivariate analysis, only lack of beta-blocker use (relative risk 0.15, 95% confidence intervals 0.05 to 0.45; p <0.0007) was identified as a predictor of appropriate ICD therapy. Of the patients who received ICD therapy, only 4 (17%) were taking beta blockers, whereas 21 of the 31 patients (68%) who did not receive ICD therapy were treated with beta blockers (p <0.0003). In patients with IDC selected for ICD implantation, the most consistent predictor of appropriate ICD therapy was lack of beta-blocker use. Attempts should be made to administer beta blockers to these patients, if tolerated.}, } @article {pmid11985914, year = {2002}, author = {Crispell, KA and Hanson, EL and Coates, K and Toy, W and Hershberger, RE}, title = {Periodic rescreening is indicated for family members at risk of developing familial dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {39}, number = {9}, pages = {1503-1507}, doi = {10.1016/s0735-1097(02)01788-6}, pmid = {11985914}, issn = {0735-1097}, support = {1R01HL58626/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cardiomyopathy, Dilated/*diagnosis/genetics/physiopathology ; Child ; Child, Preschool ; Echocardiography ; Electrocardiography ; Family ; Female ; Humans ; Infant ; Male ; Middle Aged ; Pedigree ; Phenotype ; Risk Factors ; Ventricular Dysfunction, Left/*diagnostic imaging ; }, abstract = {OBJECTIVES: This study evaluated the role of clinical rescreening of family members at risk for familial dilated cardiomyopathy (FDC).

BACKGROUND: Familial dilated cardiomyopathy is a genetic cardiomyopathy that usually is transmitted in an autosomal dominant pattern and may underlie from one-quarter to one-half of idiopathic dilated cardiomyopathy (IDC) diagnoses. Thus, FDC may present with advanced heart failure (HF) or sudden cardiac death (SCD). Because FDC may respond to medical intervention, we have previously recommended that screening of first-degree relatives (parents, siblings, children) of patients diagnosed with IDC be undertaken to rule out FDC, and that with a diagnosis of FDC in the kindred, unaffected but at-risk family members be rescreened every three to five years. METHODS; Follow-up screening (history, examination, electrocardiogram, echocardiography) of a large family with FDC was performed six years after initial screening. Of 68 family members who underwent rescreening, two (one with left ventricular enlargement only, one with a left bundle branch block) presented with advanced HF and SCD, respectively. Two additional subjects, asymptomatic at initial screening, were also affected with FDC at follow-up.

CONCLUSIONS: Considerable vigilance for disease presentation and progression is indicated in at-risk members of a kindred with FDC, especially those with incipient FDC.}, } @article {pmid11972869, year = {2002}, author = {Domoto, H and Tsuda, H and Miyakawa, K and Shinoda, A and Nanasawa, T}, title = {Invasive ductal carcinoma associated with tubular adenoma of the breast.}, journal = {Pathology international}, volume = {52}, number = {3}, pages = {244-248}, doi = {10.1046/j.1440-1827.2002.01338.x}, pmid = {11972869}, issn = {1320-5463}, mesh = {Adenoma/diagnostic imaging/*pathology/therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy, Needle ; Breast Neoplasms/diagnostic imaging/*pathology/therapy ; Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/*pathology/therapy ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Lymph Node Excision ; Mammography ; Mastectomy ; Methotrexate/administration & dosage ; Middle Aged ; Neoplasms, Multiple Primary/diagnostic imaging/*pathology/therapy ; Radiotherapy ; Treatment Outcome ; Ultrasonography ; }, abstract = {We report an extremely rare case of the colocalization of a tubular adenoma and an invasive ductal carcinoma occurring in a 55-year-old woman. Following radiographical evaluation, fine-needle aspiration cytology of the left breast tumor was undertaken. Because cytological examination revealed malignancy, a partial mastectomy was performed. Histologically, the tumor (measuring 1.7 x 1.3 cm) comprised two distinct parts: tubular adenoma and invasive ductal carcinoma. The invasive ductal carcinoma showed a solid pattern, high nuclear and structural atypia and frequent mitotic figures, while the tubular adenoma consisted of a proliferation of small ducts lined by single layers of epithelial and myoepithelial cells with bland nuclei and inconspicuous nucleoli. The histological boundary was clearly defined between the tubular adenoma and the invasive ductal carcinoma, and between the tubular adenoma and the surrounding breast tissue. The current case might be a collision between separate tubular adenoma and invasive ductal carcinoma, but the malignant transformation of a tubular adenoma cannot be ruled out. Both the long-term observation of this case and analysis of more cases may enable us to determine the histological characteristics and clinical significance of invasive ductal carcinoma associated with tubular adenoma.}, } @article {pmid11967758, year = {2002}, author = {Emir, H and Eroğlu, E and Tekant, G and Büyükünal, C and Danişmend, N and Söylet, Y}, title = {Urodynamic findings of posterior urethral valve patients.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {12}, number = {1}, pages = {38-41}, doi = {10.1055/s-2002-25093}, pmid = {11967758}, issn = {0939-7248}, mesh = {Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Urethra/*abnormalities/physiopathology ; Urinary Bladder/physiopathology ; Urinary Bladder Neck Obstruction/etiology/physiopathology ; *Urodynamics ; }, abstract = {The most frequently observed cause of obstructed bladder in children is the posterior urethral valve (PUV). In this report, we analysed the urodynamic findings of 26 patients whose valves were fulgurated 12.6 months previously (range: 2 days - 8 years,after the fulguration). The mean age of the patients at the time of the procedure was 4.5 years (range: 2 months -13 years). Bladder capacity was decreased in 15, increased in 6, and normal in 5 patients; hypo-compliance was observed in 13, hyper-compliance was observed in 4, and normo-compliance was observed in 9 children. Generally, hypo-compliance and decreased bladder capacity was more frequent in patients younger than 4 years of age. There were 10 patients with instable detrusor contractions(IDC) and high residual urine was present in 8 patients. Eight patients developed chronic renal failure and 6 of these patients had high residual urine. All the patients who required bladder augmentation during follow-up were the ones treated after 2.5 years of age; 4 of these 5 patients had hypo-compliance and low bladder capacity on urodynamic studies. In conclusion, all patients with PUV had pathological urodynamic findings that could change with age, and early relief of the infravesical obstruction could have an improving effect on bladder function. Urodynamic investigations may help us to design the proper treatment according to the bladder function.}, } @article {pmid11965722, year = {1999}, author = {Popovska, S and Iordanov, I and Betova, T and Baĭchev, G and Deliĭski, T}, title = {[Grading intraductal breast carcinoma].}, journal = {Akusherstvo i ginekologiia}, volume = {38}, number = {1}, pages = {46-49}, pmid = {11965722}, issn = {0324-0959}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Female ; Humans ; }, abstract = {Mammographic screening has led to increased detection of intraductal carcinoma of the breast (IdC). IdC is y heterogeneous disorder with different clinical outcomes. The study was designed to confirm consensibility of the three-tiered classification, accepted by Thomas Jefferson University Consensus Conference since 1997. The study population comprised 30 patients with IdC including patients with T1 mic and T1a. Sixty percent of IdC were classified as II-nd grade, 27% were III-rd grade and 13% as I-st grade. 20% of IdC exhibited heterogenity of grade. The cases with cribriform and papillary architecture were 1-st or II-nd grades. The other cases with comedo and solid architecture we are II-nd or III-rd grades. The cases with invasive component (T1 mic u T1a) were 25%--I-st grade, 75%--II-nd grade and III-rd grade--87.5%. In conclusion, the grading of IdC could y prognostic factor in far long term prognosis of patients with those lesions.}, } @article {pmid11964042, year = {2002}, author = {Bratthauer, GL and Tavassoli, FA}, title = {Lobular intraepithelial neoplasia: previously unexplored aspects assessed in 775 cases and their clinical implications.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {440}, number = {2}, pages = {134-138}, doi = {10.1007/s00428-001-0541-5}, pmid = {11964042}, issn = {0945-6317}, mesh = {Breast Neoplasms/*pathology ; Carcinoma in Situ/classification/*pathology ; Carcinoma, Intraductal, Noninfiltrating/pathology ; Carcinoma, Lobular/*pathology ; Disease Progression ; Female ; Humans ; Neoplasms, Second Primary ; Precancerous Conditions/*pathology ; Retrospective Studies ; }, abstract = {Lobular intraepithelial neoplasia (LIN) is currently considered a risk factor for the development of invasive breast cancer of varying morphologies (ductal or lobular) and prognoses in either breast. The reason for the high frequency (50%) of subsequent development of invasive ductal cancers remains unclear and the issue unexplored. A total of 775 LIN cases were retrieved from the Armed Forces Institute of Pathology files and separated into three groups using our three-tiered grading system. The presence or absence of simultaneous invasive cancer (ductal or lobular type) and various grades of ductal intraepithelial neoplasia (DIN) were noted for each case and correlated with the grade of LIN. Of the 775 cases, 80% qualified as LIN 2, with the other 20% being relatively evenly split between LIN 1 and LIN 3. Of the 775 cases, 163 cases were pure LIN, while invasive carcinoma was present in 140 cases. The remaining 472 cases were associated with various grades of DIN. The frequency of associated invasive carcinomas (ductal and lobular) increased from 14% in LIN 1 to 23% in LIN 3. Remarkably, while the frequency of invasive lobular carcinoma increased dramatically from 11% in LIN 1 to 86% in LIN 3, the frequency of invasive ductal carcinoma markedly decreased with advancing grade of LIN from 89% in LIN 1 to 14% in LIN 3. Among the cases of LIN unassociated with invasive carcinoma, DIN was present in 75% of LIN 1, 75% of LIN 2, and 66% of LIN 3 cases. The grade of DIN was directly proportional to the grade of LIN. Based on the higher frequency of invasive lobular carcinoma associated with LIN 3, biopsies with LIN 3 should be evaluated diligently for the presence of an associated invasive lobular carcinoma. Furthermore, an excisional biopsy should be performed when LIN 3 is observed in a core biopsy. The high frequency of DIN associated with LIN might suggest that the subsequent invasive ductal carcinomas originate from the associated DIN and that some of this may represent a different phenotype of the same cells that form the LIN lesion. It is also possible that the neoplastic cells may reflect or retain stem cell characteristics with plasticity and the capacity to attain or progress into either a ductal or lobular invasive phenotype.}, } @article {pmid11956603, year = {2002}, author = {Cayre, A and Cachin, F and Maublant, J and Mestas, D and Feillel, V and Ferrière, JP and Kwiaktowski, F and Chevillard, S and Finat-Duclos, F and Verrelle, P and Penault-Llorca, F}, title = {Single static view 99mTc-sestamibi scintimammography predicts response to neoadjuvant chemotherapy and is related to MDR expression.}, journal = {International journal of oncology}, volume = {20}, number = {5}, pages = {1049-1055}, pmid = {11956603}, issn = {1019-6439}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis ; Adult ; Aged ; Antigens, CD/biosynthesis ; Breast Neoplasms/*diagnosis/mortality ; *Chemotherapy, Adjuvant ; Drug Resistance, Neoplasm ; Female ; Humans ; Mammography/*methods ; *Membrane Glycoproteins ; Middle Aged ; Phenotype ; Prognosis ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Technetium Tc 99m Sestamibi/*pharmacology ; Tetraspanin 29 ; }, abstract = {We examined the relevance of a pre-treatment single static view 99mTc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following completion of anthracycline-based chemotherapy, clinical, mammographic, sonographic and pathological responses were determined. 99mTc-sestamibi scintimammography predicted the reduction of tumor size measured by sonography and the pathological response according to Sataloff classification (p<0.05) and tend to predict pathological response according to Chevallier (p<0.1). A negative 99mTc-sestamibi scintimammography predicted chemoresistance with a specificity of 100%. Uptake of 99mTc-sestamibi was inversely correlated to the expression of MDR1 (p<0.05) in invasive ductal carcinoma. A pre-treatment single-view 99mTc-sestamibi scintimammography is an excellent predictor of MDR1 chemoresistance and was highly specific of a lack of pathological response to chemotherapy.}, } @article {pmid11956269, year = {2002}, author = {Diller, L and Medeiros Nancarrow, C and Shaffer, K and Matulonis, U and Mauch, P and Neuberg, D and Tarbell, NJ and Litman, H and Garber, J}, title = {Breast cancer screening in women previously treated for Hodgkin's disease: a prospective cohort study.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {20}, number = {8}, pages = {2085-2091}, doi = {10.1200/JCO.2002.08.031}, pmid = {11956269}, issn = {0732-183X}, mesh = {Adult ; Breast Neoplasms/epidemiology/*prevention & control ; Female ; Hodgkin Disease/*radiotherapy ; Humans ; Mammography ; Middle Aged ; Neoplasms, Second Primary/*prevention & control ; Prospective Studies ; Risk Factors ; Survivors ; }, abstract = {PURPOSE: Young women who are exposed to chest irradiation for Hodgkin's disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors.

PATIENTS AND METHODS: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated > or = 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography. Annual follow-up was conducted through medical records, telephone, and/or mailed questionnaires.

RESULTS: At baseline, women were often unaware of their increased risk of breast cancer; 40% (35 of 87) reported themselves to be at equal or lower risk than women of the same age. Only 47% (41 of 87) reported having had a mammogram in the previous 24 months. Women who had received information from an oncologist were more likely to assess correctly their risk than women who received information from other sources (P <.001). Ten women developed 12 breast cancers (ductal carcinoma-in-situ [n = 2], invasive ductal carcinoma [n = 10]) during the study; two were diagnosed at study entry, and 10 during follow-up (median, 3.1 years). All cancers were evident on mammogram, and eight of 10 invasive cancers were node negative.

CONCLUSION: Practitioners who care for women after HD therapy need to educate patients regarding their risks and begin early screening. Screening by mammography can detect small, node-negative breast cancers in these patients.}, } @article {pmid11955332, year = {2002}, author = {Song, M and Mi, X and Li, B and Zhu, J and Gao, Y and Cui, S and Song, J}, title = {[Expression of telomerase genes in mamary atypical ductal hyperplasia].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {31}, number = {1}, pages = {30-33}, pmid = {11955332}, issn = {0529-5807}, mesh = {Breast Neoplasms/*enzymology/pathology ; Carcinoma, Intraductal, Noninfiltrating/*enzymology/pathology ; DNA-Binding Proteins ; Female ; *Gene Expression ; Humans ; RNA, Messenger ; Telomerase/*genetics ; }, abstract = {OBJECTIVE: To investigate the relationship of telomerase genes and the malignant transformation of atypical mammary ductal hyperplasia.

METHODS: Telomerase genes hTR and hTRT in 50 cases of mammary hyperplasia (the cases included 6 benign hyperplasia, 9 mild atypical hyperplasia, 12 medium atypical hyperplasia, 23 severe atypical hyperplasia) and 26 cases of breast carcinoma were detected by in situ hybridization.

RESULTS: The expression of hTR and hTRT mRNA were weak or negative in benign hyperplasia (1/6, 0), weaker in mild-moderate atypical hyperplasia (2/9, 1/9, 4/12, and 3/12), strong in severe atypical hyperplasia (14/23, 60.9% and 12/23, 52.1%), while very strong expression (23/26, 88.5% and 21/25, 80.8%) in carcinoma of the breast. The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypital hyperplasia and intraductal carcinoma was not significant (P > 0.05).

CONCLUSIONS: Telmerase genes (hTR, hTRT) expression is closely related to the malignant transformation of atypical hyperplasia. The reactivated telomerase may play a crucial role in the development of breast cancer.}, } @article {pmid11929776, year = {2002}, author = {Zimmer, MI and Larregina, AT and Castillo, CM and Capuano, S and Falo, LD and Murphey-Corb, M and Reinhart, TA and Barratt-Boyes, SM}, title = {Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS.}, journal = {Blood}, volume = {99}, number = {8}, pages = {2859-2868}, doi = {10.1182/blood.v99.8.2859}, pmid = {11929776}, issn = {0006-4971}, support = {AI43664/AI/NIAID NIH HHS/United States ; AI43916/AI/NIAID NIH HHS/United States ; HL62056/HL/NHLBI NIH HHS/United States ; RR00119/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/analysis ; Chemotaxis/immunology ; Dendritic Cells/immunology/*pathology/virology ; *Homeostasis ; Immunophenotyping ; Langerhans Cells/immunology/*pathology/virology ; Lymph Nodes/pathology/virology ; Macaca mulatta ; Models, Animal ; Simian Acquired Immunodeficiency Syndrome/*pathology ; }, abstract = {Langerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7. LCs migrated normally from skin in response to contact sensitization in monkeys with acute SIV infection. In contrast, LC migration from skin was markedly impaired during AIDS, associated with a reduction in antigen-bearing DCs in draining lymph nodes. Lymph node IDCs were increased in proportion during acute SIV infection and had an activated phenotype, whereas during AIDS IDCs had significantly lower expression of CD40 and the activation marker CD83. IDCs from monkeys with AIDS were refractory to stimulation with CD40L, demonstrating a functional consequence of decreased CD40 expression. SIV-infected DCs were not identified in lymph nodes or skin of monkeys with AIDS, suggesting an indirect effect of infection on DC populations in vivo. These data indicate that DCs are mobilized to lymph nodes during acute SIV infection, but that during AIDS this process is suppressed, with LC migration and IDC activation being impaired. We conclude that disruption of DC homeostasis may play a role in immunopathology induced by human immunodeficiency virus and suggest that therapeutic strategies targeting DCs may have limited efficacy during AIDS.}, } @article {pmid11921196, year = {2002}, author = {Russo, J and Tahin, Q and Lareef, MH and Hu, YF and Russo, IH}, title = {Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens.}, journal = {Environmental and molecular mutagenesis}, volume = {39}, number = {2-3}, pages = {254-263}, doi = {10.1002/em.10052}, pmid = {11921196}, issn = {0893-6692}, support = {CA87230/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast/*cytology ; Breast Neoplasms/etiology/genetics ; Carcinogens/*adverse effects ; Cell Transformation, Neoplastic/*chemically induced/pathology ; Epithelial Cells/*drug effects/pathology ; Estrogens/*adverse effects ; Female ; Humans ; Mice ; }, abstract = {Sporadic breast cancer, the most common cancer diagnosed in American and Northern European women, is gradually increasing in incidence in most Western countries. Prevention would be the most efficient way of eradicating this disease. This goal, however, cannot be accomplished until the specific agent(s) or mechanisms that initiate the neoplastic process are identified. Experimental studies have demonstrated that mammary cancer is a hormone-dependent multistep process that can be induced by a variety of compounds and mechanisms, that is, hormones, chemicals, radiation, and viruses, in addition to or in combination with genetic factors. Although estrogens have been shown to play a central role in breast cancer development, their carcinogenicity on human breast epithelial cells (HBECs) has not yet been clearly demonstrated. Breast cancer initiates in the undifferentiated lobules type 1, which are composed of three cell types: highly proliferating cells that are estrogen-receptor negative (ER-), nonproliferating cells that are ER positive (ER+), and very few (<1%) ER+ cells that proliferate. Interestingly, endogenous 17beta-estradiol (E(2)) is metabolized by the cytochrome P450 enzyme isoforms CYP1A1 and CYP1B1, which also activate benzo[a]pyrene (B[a]P), a carcinogen contained in cigarette smoke. We postulate that if estrogens are carcinogenic in HBECs, they should induce the same transformation phenotypes induced by chemical carcinogens and ultimately genomic changes observed in spontaneously developing primary breast cancers. To test this hypothesis we compared the transforming potential of E(2) on the HBEC MCF-10F with that of B[a]P. Both E(2) and B[a]P induced anchorage-independent growth, colony formation in agar methocel, and loss of ductulogenic capacity in collagen gel, all parameters indicative of cell transformation. In addition, the DNA of E(2)-transformed cells expressed LOH in chromosome 11 at 11q23.3, 11q24.2-q25, and LOH at 13q12-q13. B[a]P-induced cell transformation was also associated with LOH at 13q12-q13 and at 17p13.2. The relevance of these findings is highlighted by the observation that E(2)- and B[a]P-induced genomic alterations in the same loci found in ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma of the breast.}, } @article {pmid11920948, year = {2002}, author = {Nakashima, K and Yamamoto, K and Al-Dirbashi, OY and Nakashima, MN}, title = {Disposition of triazolam in the rat by brain microdialysis and semi-micro column high-performance liquid chromatography with UV absorbance detection.}, journal = {Biomedical chromatography : BMC}, volume = {16}, number = {3}, pages = {219-223}, doi = {10.1002/bmc.128}, pmid = {11920948}, issn = {0269-3879}, mesh = {Animals ; Anti-Anxiety Agents/blood/*pharmacokinetics ; Brain/*metabolism ; Calibration ; Chromatography, High Pressure Liquid ; Male ; Microdialysis ; Rats ; Rats, Wistar ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrophotometry, Ultraviolet ; Triazolam/blood/*pharmacokinetics ; }, abstract = {A semi-micro column high-performance liquid chromatography with ultraviolet detection for the determination of triazolam is described. The method was applied to determine plasma and brain microdialysate concentrations of triazolam after single intravenous bolus of 2.5 mg/kg to rat. The separation was achieved on a 250 x 1.5 mm i.d. C(18) column and the column effluent was monitored at 222 nm. The detection limits at a signal-to-noise ratio of 3 obtained using spiked plasma and artificial cerebrospinal fluid were 2.1 and 0.7 ng/mL, respectively. The intra- and inter-day reproducibility of the present method were satisfactory with the highest relative standard deviation of 9.1 (n > or = 5). The present method was successfully applied to study the disposition of triazolam in rat (n = 5) by analyzing plasma and brain microdialysate samples.}, } @article {pmid11920633, year = {2002}, author = {Schnack Nielsen, B and Rank, F and Engelholm, LH and Holm, A and Danø, K and Behrendt, N}, title = {Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells.}, journal = {International journal of cancer}, volume = {98}, number = {5}, pages = {656-664}, doi = {10.1002/ijc.10227}, pmid = {11920633}, issn = {0020-7136}, mesh = {Animals ; Antibody Formation ; Blotting, Western ; Breast/*metabolism ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Cross-Linking Reagents ; Female ; Fluorescent Antibody Technique ; Humans ; In Situ Hybridization ; *Mannose-Binding Lectins ; Membrane Glycoproteins/*genetics/metabolism ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; RNA, Messenger/metabolism ; Rabbits ; Receptors, Cell Surface/*genetics/metabolism ; Stromal Cells/*metabolism/pathology ; Transcription, Genetic ; U937 Cells/metabolism/pathology ; }, abstract = {The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new uPAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically recognized uPARAP in Western blotting and gave a strong signal in immunohistochemistry. The immunohistochemic localization pattern was found to be identical to that of uPARAP mRNA as determined in parallel by in situ hybridization. uPARAP expression was then studied in both benign and malignant breast lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor-associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling.}, } @article {pmid11920593, year = {2002}, author = {Umekita, Y and Ohi, Y and Sagara, Y and Yoshida, H}, title = {Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor-negative breast cancer patients.}, journal = {International journal of cancer}, volume = {98}, number = {3}, pages = {415-418}, doi = {10.1002/ijc.10151}, pmid = {11920593}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology/surgery ; Carcinoma, Ductal, Breast/*metabolism/pathology/surgery ; Cyclin D1/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/pathology ; Mastectomy ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/metabolism ; Survival Rate ; Treatment Outcome ; }, abstract = {CyclinD1 plays a critical role in regulating cell cycle progression. CyclinD1 mRNA and protein are overexpressed in approximately 50% of primary breast cancer cases. However, its clinical significance as a predictive factor remains unclear. One hundred and seventy-three female patients diagnosed with invasive ductal carcinoma who had undergone a mastectomy (161 patients) or breast-conserving surgery (12 patients) were followed up for 6-119 months (median 86 months) postoperatively. Immunoreactivity for monoclonal anti-cyclinD1 antibody (clone DCS-6) with paraffin-embedded carcinoma tissues was investigated using a labeled streptavidin-biotin method. Overexpression of cyclinD1 was found in 42% (73 of 173), and strongly correlated with estrogen receptor (ER) expression (p < 0.000001). Univariate analysis revealed no association between overexpression of cyclinD1 and overall survival or relapse-free survival in all patient groups. However, in the ER-negative subgroup (n = 75), overexpression of cyclinD1 was significantly correlated with shorter overall survival (p = 0.018) and relapse-free survival (p = 0.014) as well as the lymph node status and tumor size. In contrast, there were no significant associations between overexpression of cyclinD1 and clinical outcome in the ER-positive subgroup. According to Cox's multivariate analysis in the ER-negative subgroup, overexpression of cyclinD1 had the most significant effect on overall survival (p = 0.02) and relapse-free survival (p = 0.0058), followed by nodal status and histologic grade. These findings suggest that overexpression of cyclinD1 is an independent prognostic indicator in ER-negative breast cancer patients.}, } @article {pmid11917580, year = {2002}, author = {Ng, WK and Poon, CS and Kong, JH}, title = {Fine needle aspiration cytology of ductal breast carcinoma with neuroendocrine differentiation. Review of eight cases with histologic correlation.}, journal = {Acta cytologica}, volume = {46}, number = {2}, pages = {325-331}, doi = {10.1159/000326729}, pmid = {11917580}, issn = {0001-5547}, mesh = {Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Neuroendocrine/pathology ; Cell Differentiation ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; }, abstract = {OBJECTIVE: To describe the fine needle aspiration cytology findings of ductal breast carcinoma with neuroendocrine differentiation and correlate them with the histologic appearance.

STUDY DESIGN: We reviewed the cytologic features of eight cases of ductal carcinoma with neuroendocrine differentiation in the files of Pamela Youde Nethersole Eastern Hospital during the three-year period 1998-2000. Immunohistochemical study for neuroendocrine markers was performed, with ultrastructural correlation.

RESULTS: All cases showed similar cytologic features. The smears were of moderate to high cellularity with predominantly dispersed or loosely cohesive tumor cells. The carcinoma cells were mostly of low cytologic grade. They possessed round and relatively uniform, eccentric nuclei; finely stippled chromatin; sometimes small, distinct nucleoli; and discrete cell borders. Abundant eosinophilic and focally granular cytoplasm was a common finding. In some of the cases there was accentuation of staining in the paranuclear region; it correlated with aggregates of dense core neurosecretory granules seen ultrastructurally. Mucoid substance was seen in the background in some of the aspirates. Histologic examination of the tumors showed invasive ductal carcinoma with an organoid growth pattern and sometimes mucinous component. The neuroendocrine differentiation was confirmed immunohistochemically.

CONCLUSION: Although this subtype of ductal carcinoma probably carries no significant prognostic value per se, it has distinct cytologic features, rendering preoperative diagnosis possible. Recognition of this entity is important in order to avoid the misdiagnosis of neuroendocrine tumor metastatic to the breast.}, } @article {pmid11914644, year = {2002}, author = {Takamura, M and Nio, Y and Yamasawa, K and Dong, M and Yamaguchi, K and Itakura, M}, title = {Implication of thymidylate synthase in the outcome of patients with invasive ductal carcinoma of the pancreas and efficacy of adjuvant chemotherapy using 5-fluorouracil or its derivatives.}, journal = {Anti-cancer drugs}, volume = {13}, number = {1}, pages = {75-85}, doi = {10.1097/00001813-200201000-00009}, pmid = {11914644}, issn = {0959-4973}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/*enzymology/pathology ; Chemotherapy, Adjuvant ; Female ; Fluorouracil/analogs & derivatives/*therapeutic use ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*drug therapy/*enzymology/pathology ; Prognosis ; Survival Rate ; Thymidylate Synthase/*metabolism ; Tissue Distribution ; Treatment Outcome ; }, abstract = {Thymidine synthase (TS) is a key enzyme in the synthesis of pyrimidine in the de novo pathway of DNA synthesis and a major target of 5-fluorouracil (5-FU), but the implications of TS regarding human pancreatic cancer have not been reported. We assessed the expression of TS in invasive ductal carcinoma (IDC) of the pancreas by immunostaining and evaluated its clinicopathological significance, especially its implications regarding the efficacy of chemotherapy with 5-FU or its derivatives. The expression of TS in the nuclei of pancreatic cancer cells in 72 primary lesions of resectable IDC and 30 distant metastases of unresectable IDC was examined by immunostaining using anti-TS polyclonal antibody and immunoreactivity was classified into three categories: negative (-), low (+) and high (2+). High TS immunoreactivity was detected in 43% (31 of 72) of the primary lesions of the resectable IDCs and in 47% (18 of 38) of the metastatic lesions of the unresectable IDCs. The high TS in primary lesions showed a significantly inverse correlation with the level of nodal involvement. High TS immunoreactivity had a significant influence on the outcome of patients with resectable IDC and the rate of survival of the high TS immunoreactivity group was significantly higher than that of the negative or low reactivity groups, although high TS immunoreactivity did not have a significant influence on survival of the patients with unresectable IDC. The implications of TS immunoreactivity regarding the efficacy of 5-FU-based adjuvant chemotherapy (ACT) was also assessed. The high TS immunoreactivity group showed significantly better survival in both the patients who received ACT and those who were treated by surgery alone, in the resectable IDC among patients with resectable IDC. In cases of unresectable IDC, there were no differences in survival between the high and low TS groups among the patients who received ACT and those who were treated by surgery. In conclusion, high TS immunoreactivity was found to be cogent in predicting the prognosis of patients with pancreatic IDC, but its implications regarding the efficacy of 5-FU-based ACT are still unclear.}, } @article {pmid11899244, year = {2001}, author = {Towbin, JA and Bowles, NE}, title = {Molecular genetics of left ventricular dysfunction.}, journal = {Current molecular medicine}, volume = {1}, number = {1}, pages = {81-90}, doi = {10.2174/1566524013364077}, pmid = {11899244}, issn = {1566-5240}, mesh = {Cardiomyopathies/*genetics/metabolism/physiopathology ; Dystrophin/genetics/*metabolism ; Echocardiography ; Humans ; Models, Biological ; Syndrome ; Ventricular Dysfunction, Left/*genetics/metabolism/physiopathology ; }, abstract = {The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure (CHF), leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device (LVAD), or cardiac transplantation. In the majority of patients the etiology is unknown, leading to the term idiopathic dilated cardiomyopathy (IDC). During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30-40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy (FDCM), the genetic basis is beginning to unfold. To date, two genes for X-linked FDCM (dystrophin, G4.5) have been identified and four genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In one form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators and dystrophin cleavage play a role in the development of LV dysfunction. In this review, we will describe the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.}, } @article {pmid11893034, year = {2002}, author = {Rosenthal, SI and Depowski, PL and Sheehan, CE and Ross, JS}, title = {Comparison of HER-2/neu oncogene amplification detected by fluorescence in situ hybridization in lobular and ductal breast cancer.}, journal = {Applied immunohistochemistry & molecular morphology : AIMM}, volume = {10}, number = {1}, pages = {40-46}, doi = {10.1097/00129039-200203000-00007}, pmid = {11893034}, issn = {1541-2016}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; Female ; *Gene Amplification ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; *Oncogenes ; }, abstract = {BACKGROUND: Abnormal expression of the HER-2/neu oncogene, a tyrosine kinase-type transmembrane growth factor receptor localized to chromosome 17q, has been associated with poor prognosis and the prediction of therapy response in invasive breast cancer. The comparative incidence and significance of HER-2/neu gene amplification for lobular and ductal breast cancer have not been previously characterized.

DESIGN: Formalin-fixed, paraffin-embedded primary breast cancer tissue sections from 71 women diagnosed with invasive lobular carcinoma were tested for HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) method using the Ventana unique sequence probe (Ventana Medical Systems, Tucson, AZ). A series of 106 cases of invasive ductal carcinoma was similarly processed and tested. Lymph node status was available for 155 (88%) of the 177 cases and 82 (46%) were lymph node-negative (LN-) and 73 (41%) were lymph node-positive (LN+). Patients were treated for a mean of 65 months (range 1-169 months).

RESULTS: 9 of 71 (13%) cases of lobular cancer featured HER-2/neu gene amplification, whereas 51 (48%) of 106 cases of ductal cancer showed amplification (P < 0.0001). On univariate analysis of combined lobular and ductal cases, HER-2/neu gene amplification detected by FISH predicted disease-related death (P < 0.0001). HER-2/neu gene amplification also predicted disease-related death in lobular cases alone (P = 0.003), LN+ lobular cases separately (P = 0.019), and LN- and LN+ ductal cases separately and alone (P < 0.0001). Multivariate analysis of the lobular group alone revealed that LN+ status (P = 0.015) and stage (P = 0.01) were independent predictors of disease-related death, and HER-2/neu gene amplification reached near significance (P = 0.086). In the ductal carcinoma group alone, HER-2/neu gene amplification (P = 0.03), lymph node status (P = 0.0001), tumor stage (P = 0.0001), and tumor grade (P = 0.044) were independent predictors of overall disease survival.

CONCLUSIONS: HER-2/neu gene amplification detected by FISH was identified at a significantly lower rate in lobular compared with ductal breast cancer. HER-2/neu gene amplification when present in lobular breast cancer is a significant adverse prognostic factor.}, } @article {pmid11889601, year = {2002}, author = {Barth, PJ and Ebrahimsade, S and Ramaswamy, A and Moll, R}, title = {CD34+ fibrocytes in invasive ductal carcinoma, ductal carcinoma in situ, and benign breast lesions.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {440}, number = {3}, pages = {298-303}, doi = {10.1007/s004280100530}, pmid = {11889601}, issn = {0945-6317}, mesh = {Actins/metabolism ; Adenoma/metabolism/*pathology ; Adult ; Aged ; Antigens, CD34/metabolism ; Breast/metabolism/*pathology ; Breast Neoplasms/metabolism/*pathology ; Carcinoma in Situ/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/*pathology ; Female ; Fibroblasts/metabolism/pathology ; Humans ; Hyperplasia/metabolism/pathology ; Immunoenzyme Techniques ; Middle Aged ; Phyllodes Tumor/metabolism/*pathology ; Stromal Cells/metabolism/pathology ; }, abstract = {The present study was undertaken in order to elucidate the question of whether the distribution of stromal CD34+ fibrocytes and smooth muscle actin (SMA)-reactive myofibroblasts differs between benign and malignant lesions of the breast. We investigated a total of 31 ductal carcinomas and 27 specimens with benign lesions of the breast (ductal hyperplasia, sclerosing adenosis, fibroadenoma, phyllodes tumor) and compared the distribution of CD34+ fibrocytes and SMA-reactive myofibroblasts. The stroma of normal breast tissue contained CD34+ fibrocytes, whereas SMA-reactive myofibroblasts were absent. All benign breast lesions exhibited stromal CD34+ fibrocytes and few lesions (fibroadenomas and phyllodes tumor) showed additional SMA-reactive myofibroblasts. In invasive breast cancer the stroma was devoid of CD34+ fibrocytes but a varying number of stromal SMA-reactive myofibroblasts was detectable. In the setting of the present study the loss of CD34+ fibrocytes was specific for invasive breast cancer and ductal carcinoma in situ, whereas SMA-reactive myofibroblasts were observed in different benign and malignant lesions. These findings may be helpful tools in distinguishing benign breast lesions (e.g., sclerosing adenosis) from invasive breast cancer and in characterizing stromal remodeling associated with invasive cancer.}, } @article {pmid11887115, year = {2002}, author = {Groah, SL and Weitzenkamp, DA and Lammertse, DP and Whiteneck, GG and Lezotte, DC and Hamman, RF}, title = {Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer.}, journal = {Archives of physical medicine and rehabilitation}, volume = {83}, number = {3}, pages = {346-351}, doi = {10.1053/apmr.2002.29653}, pmid = {11887115}, issn = {0003-9993}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Catheters, Indwelling/*adverse effects ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Rehabilitation Centers ; Risk Factors ; Sex Distribution ; Spinal Cord Injuries/*rehabilitation ; Urinary Bladder Neoplasms/epidemiology/*etiology/mortality ; }, abstract = {OBJECTIVES: To evaluate whether the risk of bladder cancer is greater in individuals with spinal cord injury (SCI) than in the general population and whether indwelling catheter (IDC) use is a significant independent risk factor for bladder cancer.

DESIGN: Historical cohort study in which subjects with SCI were stratified according to bladder management method and followed for the development of bladder cancer.

SETTING: A large rehabilitation hospital in the Spinal Cord Injury Model Systems.

PARTICIPANTS: A total of 3670 patients with SCI who were evaluated for bladder cancer on at least 1 occasion by cystoscopy over a period of 1 to 47 years.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Bladder cancer occurring after SCI determined by diagnosis at our facility, by subject report, or by report of next of kin.

RESULTS: Twenty-one cases of bladder cancer were found in the 3670 study participants. The risk of bladder cancer for subjects with SCI using IDC is 77 per 100,000 person-years, corresponding to an age- and gender-adjusted standardized morbidity ratio (SMR) of 25.4 (95% confidence interval [CI], 14.0--41.9) when compared with the general population. After controlling for age at injury, gender, level and completeness of SCI, history of bladder calculi, and smoking, those using solely IDC had a significantly greater risk of bladder cancer (relative risk [RR] = 4.9; 95% CI, 1.3--13.8) than those using nonindwelling methods. Mortality caused by bladder cancer in individuals with SCI was significantly greater than that of the US population (SMR = 70.6; 95% CI, 36.9--123.3).

CONCLUSIONS: Bladder cancer risk and mortality are heightened in SCI compared with the general population. IDC is a significant independent risk factor for the increased risk of and mortality caused by bladder cancer in the SCI population.}, } @article {pmid11884044, year = {2002}, author = {Leidenius, MH and Leppänen, EA and Tykkä, HT and von Smitten, KA}, title = {The role of Tc99m-sestamibi scintimammography in combination with the triple assessment of primary breast cancer.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {28}, number = {2}, pages = {108-112}, doi = {10.1053/ejso.2001.1217}, pmid = {11884044}, issn = {0748-7983}, mesh = {Aged ; Biopsy, Needle ; Breast Neoplasms/diagnosis/*diagnostic imaging/*pathology/surgery ; Female ; Humans ; Mammography/*methods ; Middle Aged ; Neoplasm Staging ; *Radiographic Image Enhancement ; Radionuclide Imaging ; Sensitivity and Specificity ; Statistics, Nonparametric ; *Technetium Tc 99m Sestamibi ; Ultrasonography/methods ; }, abstract = {AIM: The aim of this study was to evaluate if Tc99m-sestamibi scintimammography in addition to the triple assessment consisting of clinical examination, mammography, breast ultrasonography and fine needle aspiration cytology (FNA) enhances the diagnosis of breast cancer and helps in avoiding unnecessary operative biopsies.

METHODS: Pre-operational scintimammography was performed within 2 weeks of operation to 46 consecutive patients with abnormal findings in clinical breast examination, mammography or ultrasonography. Three patients had abnormalities in both breasts. Histological diagnosis was obtained in all 49 cases.

RESULTS: The histological diagnosis was benign in 18 (37%) cases and malignant in 31 (63%) cases. The overall sensitivity of scintimammography was 77% and the specificity was 61%. The sensitivity of scintimammography was 95% in invasive ductal carcinoma, 50% in invasive lobular carcinoma and 25% in ductal carcinoma in situ. Scintimammography showed 100% sensitivity in cases with invasive carcinoma, with highly suspicious findings for malignancy in the other examinations. The sensitivity was 63% in cases with indeterminate or contradictory findings in mammography, ultrasonography and FNA.

CONCLUSIONS: Adding scintimammography to the triple assessment does not seem to be helpful in the diagnosis of breast abnormalities because of low sensitivity in malignant cases with a challenging diagnosis by mammography, ultrasonography and FNA, and because of low overall specificity.}, } @article {pmid11869841, year = {2002}, author = {Grimm, W and Hoffmann J, Jü and Müller, HH and Maisch, B}, title = {Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%.}, journal = {Journal of the American College of Cardiology}, volume = {39}, number = {5}, pages = {780-787}, doi = {10.1016/s0735-1097(01)01822-8}, pmid = {11869841}, issn = {0735-1097}, mesh = {Adolescent ; Adult ; Aged ; Cardiac Output, Low/*complications/physiopathology ; Cardiomyopathy, Dilated/*complications/physiopathology ; *Defibrillators, Implantable ; Electrocardiography ; *Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Stroke Volume/*physiology ; Syncope/*etiology/physiopathology/*therapy ; Tachycardia, Ventricular/*etiology/physiopathology/*therapy ; Time Factors ; Ventricular Fibrillation/*etiology/physiopathology/*therapy ; }, abstract = {OBJECTIVES: This study investigated the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions for ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with idiopathic dilated cardiomyopathy (IDC) and nonsustained VT in the presence of a left ventricular ejection fraction below 30%, versus in patients with syncope and patients with a history of VT or VF.

BACKGROUND: To date, only limited information is available about the prophylactic use of ICDs in patients with IDC.

METHODS: From January 1993 to July 2000, 101 patients with IDC underwent implantation of ICDs with electrogram storage capability at our institution. Patients were placed into one of three groups according to their clinical presentation: asymptomatic or mildly symptomatic nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% (49 patients, prophylactic group), unexplained syncope or near syncope (26 patients, syncope group) and a history of sustained VT or VF (26 patients, VT/VF group).

RESULTS: During 36 +/- 22 months follow-up, 18 of 49 patients (37%) in the prophylactic group received appropriate shocks for VT or VF, compared with 8 of 26 patients (31%) in the syncope group and with 9 of 26 patients (35%) of the VT/VF group. Multivariate Cox analysis of baseline clinical variables identified left ventricular ejection fraction, atrial fibrillation and a history of sustained VT or VF as predictors for appropriate ICD interventions during follow-up.

CONCLUSIONS: Patients with IDC and prophylactic ICD implantation for nonsustained VT in the presence of a left ventricular ejection fraction < or = 30% had an incidence of appropriate ICD interventions similar to that of patients with a history of syncope or sustained VT or VF. These findings indicate that ICDs may have a role in not only secondary but also primary prevention of sudden death in IDC.}, } @article {pmid11866953, year = {2001}, author = {Han, A and Xiong, M and Li, Z and Liang, Y}, title = {[E-cadherin associated protein expression and its significance in invasive lobular carcinoma and invasive ductal carcinoma of breast].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {30}, number = {1}, pages = {27-30}, pmid = {11866953}, issn = {0529-5807}, mesh = {Adult ; Aged ; Breast Neoplasms/*metabolism/pathology ; Cadherins/*metabolism ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology ; Carcinoma, Lobular/*metabolism/pathology ; Cell Adhesion ; Cytoskeletal Proteins/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Trans-Activators/metabolism ; alpha Catenin ; beta Catenin ; }, abstract = {OBJECTIVE: To study E-cadherin associated proteins alpha-, beta-, gamma-catenin expression and their significance in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of breast.

METHODS: Immunohistochemistry staining (labeled streptavidin-biotin method) was used to detect alpha-, beta-, gamma-catenin expression in invasive breast carcinoma (19 cases of ILC and 32 cases of IDC).

RESULTS: The loss and reduction rate of alpha-, beta-, gamma-catenin expression in ILC was 78.9% (15 cases), 52.6% (10 cases) and 84.2% (16 cases), respectively. The rate of alpha-, beta-, gamma-catenin expression showing loss and reduction in IDC was 75.0% (24 cases), 43.8% (14 cases) and 81.3% (26 cases), respectively. The staining intensity of alpha-, beta-, gamma-catenin expression in invasive carcinoma of breast was weaker than that in foci of carcinoma in situ (semiquantitative grading). There was a positive relationship between the expression of alpha-catenin and beta-catenin in invasive breast carcinoma. No significant association was seen between reduced protein expression of alpha-, beta-, gamma-catenin and the development of lymph node metastasis.

CONCLUSION: alpha-, beta-, gamma-catenin expression was almost identical in ILC and IDC of breast, showing significant loss and reduction of protein expression in the carcinoma cells of invasive breast carcinoma, suggesting that alpha-, beta-, gamma-catenin may lose their normal adherent ability in the pathogenesis of invasive breast carcinoma.}, } @article {pmid11866083, year = {2002}, author = {Mahlfeld, K and Kayser, R and Grasshoff, H}, title = {Permanent thoracic myelopathy resulting from herniation of a calcified intervertebral disc in a child.}, journal = {Journal of pediatric orthopedics. Part B}, volume = {11}, number = {1}, pages = {6-9}, doi = {10.1097/00009957-200201000-00002}, pmid = {11866083}, issn = {1060-152X}, mesh = {Calcinosis/*complications ; Child ; Female ; Humans ; Intervertebral Disc Displacement/complications/*diagnosis/surgery ; Laminectomy ; Magnetic Resonance Imaging ; Recovery of Function ; Retrospective Studies ; Spinal Cord Diseases/*etiology ; Thoracic Vertebrae/pathology ; }, abstract = {This retrospective study was made to illustrate the rare occurrence of neurologic deficits resulting from intervertebral disc calcification (IDC) in a child. Most authors agree that juvenile IDC is usually a benign, self-limiting disease with excellent prognosis. The symptoms subside spontaneously in 95% of patients. Conservative treatment is therefore usually sufficient. Reviewing the English-speaking literature, only two further cases of operated juvenile IDC with myelopathy have been published. In the current report, we describe a case of permanent thoracic myelopathy resulting from juvenile IDC treated by urgent decompressive thoracic laminectomy. At the 3-year follow-up examination, the patient had not recovered fully. Persisting deficits in motor and sensory function were observed.}, } @article {pmid11862580, year = {2002}, author = {Hanson, EL and Jakobs, PM and Keegan, H and Coates, K and Bousman, S and Dienel, NH and Litt, M and Hershberger, RE}, title = {Cardiac troponin T lysine 210 deletion in a family with dilated cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {8}, number = {1}, pages = {28-32}, doi = {10.1054/jcaf.2002.31157}, pmid = {11862580}, issn = {1071-9164}, support = {1R01HL58626-01/HL/NHLBI NIH HHS/United States ; }, mesh = {Cardiomyopathy, Dilated/*genetics ; Cardiomyopathy, Hypertrophic, Familial/genetics ; Exons ; Female ; Gene Deletion ; Humans ; Lysine/genetics ; Male ; Middle Aged ; Mutation ; Pedigree ; Troponin T/*genetics ; }, abstract = {BACKGROUND: The gene for cardiac troponin T (TNNT2) is 1 of 7 autosomal disease genes implicated in familial dilated cardiomyopathy (FDC). Identical deletions in exon 13 of TNNT2 have been reported in 2 families with FDC, but little is known about the frequency of this deletion among patients with FDC and idiopathic dilated cardiomyopathy (IDC) and the associated phenotype.

METHODS AND RESULTS: Exon 13 of the cardiac troponin T gene was sequenced in 61 subjects with FDC and 53 subjects with IDC. A 3-base pair deletion (DeltaLys210), identified in 1 family with at least 7 clinically affected family members, is reported. Age of disease onset and disease severity varied widely among affected individuals; phenotypic findings included dilated cardiomyopathy, sudden cardiac death, conduction system disease including atrial fibrillation and atrioventricular block, and heart failure. Sudden-onset, rapidly progressive disease was observed in younger individuals.

CONCLUSIONS: Cardiac troponin T exon 13 lysine deletions can cause FDC of varying severity and are an important but uncommon cause of FDC.}, } @article {pmid11857490, year = {2002}, author = {Farabegoli, F and Champeme, MH and Bieche, I and Santini, D and Ceccarelli, C and Derenzini, M and Lidereau, R}, title = {Genetic pathways in the evolution of breast ductal carcinoma in situ.}, journal = {The Journal of pathology}, volume = {196}, number = {3}, pages = {280-286}, doi = {10.1002/path.1048}, pmid = {11857490}, issn = {0022-3417}, mesh = {Breast Neoplasms/*genetics/mortality ; Carcinoma in Situ/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Chi-Square Distribution ; Disease-Free Survival ; Female ; Humans ; *Loss of Heterozygosity ; Neoplasms, Multiple Primary/*genetics/mortality ; Polymerase Chain Reaction ; }, abstract = {The patterns of allelic loss in 28 cases of pure ductal carcinoma in situ (DCIS) and 25 cases of DCIS associated with invasive ductal carcinoma (IDC) were compared, in order to define whether pure DCIS represented an earlier stage than DCIS associated with IDC in the progression of breast carcinoma. To this aim, the polymerase chain reaction (PCR) was performed on microdissected normal and neoplastic breast tissue, formalin-fixed and paraffin-embedded. Fifteen microsatellite markers were examined, on chromosomes 1p, 3p, 7q, 11q, 12p, 13q, 16q and 17q, mostly focused on regions altered in breast cancer. Loss of heterozygosity (LOH) was greater in pure DCIS than in the DCIS component associated with IDC for 11 out of 15 markers. The difference was statistically significant for D13S260 and D17S800 (p=0.008 and p=0.01, respectively). DCIS associated with IDC showed a lesser degree of alteration than the synchronous IDC component for ten out of 15 markers. In contrast, LOH at D11S1816 and D16S318 was lower in pure DCIS than in DCIS associated with IDC and even greater in the IDC component. These results confirm that DCIS is a possible but not an obligate precursor of invasive breast cancer and suggest that pure DCIS and DCIS associated with IDC may be genetically distinct. The evolution from DCIS to IDC may follow multiple pathways and not a linear model.}, } @article {pmid11842356, year = {2002}, author = {Millet, GP and Chollet, D and Chalies, S and Chatard, JC}, title = {Coordination in front crawl in elite triathletes and elite swimmers.}, journal = {International journal of sports medicine}, volume = {23}, number = {2}, pages = {99-104}, doi = {10.1055/s-2002-20126}, pmid = {11842356}, issn = {0172-4622}, mesh = {Adaptation, Physiological ; Adult ; Analysis of Variance ; Arm/*physiology ; Biomechanical Phenomena ; Humans ; Leg/physiology ; Motor Skills ; Swimming/*physiology ; Videotape Recording ; }, abstract = {The aim of this study was to compare the arm coordination in 19 elite triathletes and 15 elite swimmers at six different velocities between 80 % and 100 % of their maximal velocity (Vmax). The different phases of the stroke (A: entry; B: pull; C: push; D: recovery) were identified by video analysis. An index of coordination (IdC) was calculated. It was the time that separated the beginning of the propulsive phase of one arm from the end of the propulsive phase of the other arm. IdC allows to express the mode of arm coordination: catch-up, IdC < 0; opposition, IdC = 0; superposition, IdC > 0. Between 80 % and 98 % Vmax, elite triathletes showed similar increases in IdC than swimmers (from -8.8 % to 2.6 % vs from -8.6 % to 0.3 %) switching from a catch-up to a superposition coordination. Between 88 % and Vmax, triathletes increased the propulsive phase (B+C) less (p < 0.01) than swimmers (3.4 % vs 8.5 %) and increased the recovery phase (0.8 %) when swimmers reduced it (-1.6 %). Between V5 and Vmax, both triathletes and swimmers had a significant (p < 0.01) difference in IdC change (-1.7 % vs 2.3 %). Moreover, triathletes reduced the propulsive phase when swimmers increased it (-0.6 % vs 3.2 %). The lower velocity of the triathletes was associated to a shorter stroke length when compared to the swimmers (1.70 m vs 2.15 m at Vmax). The stroke rates were not statistically different (55.1 vs 51.2 stroke x min(-1) at Vmax). Thus, monitoring IdC and stroke length is recommended for triathletes mainly at maximal velocity.}, } @article {pmid11827073, year = {2000}, author = {Edel, MJ and Harvey, JM and Papadimitriou, JM}, title = {Comparison of vascularity and angiogenesis in primary invasive mammary carcinomas and in their respective axillary lymph node metastases.}, journal = {Clinical & experimental metastasis}, volume = {18}, number = {8}, pages = {695-702}, pmid = {11827073}, issn = {0262-0898}, mesh = {Breast Neoplasms/*blood supply/pathology ; Carcinoma, Ductal, Breast/*blood supply/pathology ; Endothelium, Vascular/pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunoenzyme Techniques ; Lymph Nodes/blood supply/pathology ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neovascularization, Pathologic/metabolism/*pathology ; }, abstract = {It is well established that the ability of a neoplasm to induce a blood supply from a pre-existing circulation (angiogenesis) is a major factor in tumour growth, invasion and metastasis. However, the angiogenic potential of metastases and their subsequent growth have not been extensively studied. The question arises: can metastatic clones induce the same level of angiogenesis as in the primary neoplasm they emanated from? In this study it is hypothesised that in the same patient the level of vascularity and angiogenesis is the same in both the primary invasive ductal carcinoma and in the axillary lymph node metastasis at the time of surgery, according to Kerbels theory of clonal-dominance. To directly address the hypothesis, morphological measures of the established blood/lymphatic circulation (vascularity) as well as estimates of angiogenesis (endothelial cell proliferation) were measured in primary tumours and directly compared to the same parameters in the corresponding lymph node metastasis in a case by case basis (n = 17). The results demonstrate varying associations between the level of vascularity and angiogenesis between matched individual tumours and their metastatic lymph nodal deposits. It is possible that either variations in the angiogenic characteristics of the metastasising clone or local or systemic promoters or inhibitors of angiogenesis influence tumour angiogenesis at the different sites.}, } @article {pmid11823735, year = {2002}, author = {Kelleher, MM}, title = {Removal of urinary catheters: midnight vs 0600 hours.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {11}, number = {2}, pages = {84-90}, doi = {10.12968/bjon.2002.11.2.9308}, pmid = {11823735}, issn = {0966-0461}, mesh = {Aged ; Catheters, Indwelling/*adverse effects ; Device Removal/*adverse effects ; Female ; Humans ; Male ; Prospective Studies ; Time Factors ; Urinary Catheterization/*adverse effects ; Urination Disorders/*etiology ; }, abstract = {In the fields of both nursing and medicine there is a dearth of published literature on the optimum time to remove indwelling urinary catheters (IDCs) following urological surgery. Tradition seems to be in favour of removing IDCs at 0600 hours despite a lack of evidence to support this practice. This study was undertaken to determine whether midnight removal of IDCs resulted in patients' resuming normal voiding patterns. A prospective clinical trial was conducted to determine the impact midnight removal of urinary catheters would have on the patients' voiding pattern, and subsequent discharge from hospital. One hundred and sixty patients were entered into the study. The patients were allocated at random to have their urinary catheter removed either at midnight or at 0600 hours. Patients who had their catheters removed at midnight passed a greater volume of urine with both their first (268 ml compared with 177 ml; P<0.0001) and second voids (322 ml compared with 195 ml; P<0.0001) than their counterparts in the 0600 group. This permitted earlier discharge from hospital. The results reported in this study support the findings of earlier research that midnight removal of IDC leads to an earlier resumption of normal voiding patterns, permits earlier discharge from hospital and appears to reduce patients' anxiety. The recommendation from this study is that there should be a change in hospital policy so that the majority of IDCs are removed at midnight.}, } @article {pmid11818015, year = {2002}, author = {Chernomordik, V and Hattery, DW and Grosenick, D and Wabnitz, H and Rinneberg, H and Moesta, KT and Schlag, PM and Gandjbakhche, A}, title = {Quantification of optical properties of a breast tumor using random walk theory.}, journal = {Journal of biomedical optics}, volume = {7}, number = {1}, pages = {80-87}, doi = {10.1117/1.1427049}, pmid = {11818015}, issn = {1083-3668}, mesh = {Absorption ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Female ; Humans ; Infrared Rays ; Light ; Mammography ; *Models, Theoretical ; Neoplasm Invasiveness ; *Optics and Photonics ; Photons ; Scattering, Radiation ; Time Factors ; }, abstract = {For the first time we use a random walk methodology based on time-dependent contrast functions to quantify the optical properties of breast tumors (invasive ductal carcinoma) of two patients. Previously this theoretical approach was successfully applied for analysis of embedded objects in several phantoms. Data analysis was performed on distributions of times of flight for photons transmitted through the breast which were recorded in vivo using a time-domain scanning mammograph at 670 and 785 nm. The size of the tumors, their optical properties, and those of the surrounding tissue were reconstructed at both wavelengths. The tumors showed increased absorption and scattering. From the absorption coefficients at both wavelengths blood oxygen saturation was estimated for the tumors and the surrounding tissue.}, } @article {pmid11812664, year = {2002}, author = {Dağdeviren, B and Akdemir, O and Eren, M and Bolca, O and Oğuz, E and Gürlertop, Y and Tezel, T}, title = {Prognostic implication of myocardial texture analysis in idiopathic dilated cardiomyopathy.}, journal = {European journal of heart failure}, volume = {4}, number = {1}, pages = {41-48}, doi = {10.1016/s1388-9842(01)00205-7}, pmid = {11812664}, issn = {1388-9842}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/*diagnostic imaging/*pathology ; Chi-Square Distribution ; Echocardiography, Doppler/*methods ; Female ; Humans ; Male ; Middle Aged ; Myocardium/*pathology/ultrastructure ; Predictive Value of Tests ; Probability ; Prognosis ; Prospective Studies ; Reference Values ; Sensitivity and Specificity ; Severity of Illness Index ; Statistics, Nonparametric ; Video Recording ; }, abstract = {BACKGROUND AND AIM: Abnormal myocardial acoustic properties have been reported in patients with idiopathic dilated cardiomyopathy (IDC). The aim of this study was to investigate the relationship between quantitative ultrasonic textural alterations of myocardium and clinical outcome in IDC.

METHODS: Baseline clinical and echocardiographic variables were obtained from 28 patients with IDC. By using a videodensitometric approach, quantitative myocardial texture analysis was performed on images obtained from septum and posterior wall (PW). Cyclic variation (CV) index of mean gray level (MGL) was calculated according to the formula: (MGLdiast-MGLsyst)/MGLdiastx100. All patients were followed for an average of 11+/-5 months for the occurrence of cardiac death or repeated hospitalization due to worsening of heart failure.

RESULTS: During follow-up, 10 patients experienced cardiac events (6 cardiac deaths and 4 heart failure events). The CV indexes of both septum and PW were significantly lower in patients with cardiac events than those of event free patients (6.8+/-9.6% vs. 13.6+/-8.2%, P<0.05 and 5.3+/-6.4% vs.15.7+/-7.2% P<0.001, respectively). Univariate analysis defined the following variables as predictors of outcome: PW-CV index (chi2=13.0, P=0.0003), transmitral E/A ratio (chi2=12.5, P=0.0004), symptom status (chi2=8.7, P=0.003), and septum-CV index (chi2=4.7, P=0.03). Multivariate stepwise regression analysis showed that the PW-CV index (chi2=7.5, P=0.006) and E/A ratio (chi2=6.5, P=0.01) were the independent predictors of outcome. The event-free survival rate of patients with PW-CV index <11% was significantly lower than those with an index > or = 11 (35.7% vs. 92.8%, P=0,001).

CONCLUSION: The assessment of severely depressed CV index provides valuable prognostic information in patients with IDC.}, } @article {pmid11809710, year = {2002}, author = {Shirakawa, K and Kobayashi, H and Heike, Y and Kawamoto, S and Brechbiel, MW and Kasumi, F and Iwanaga, T and Konishi, F and Terada, M and Wakasugi, H}, title = {Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft.}, journal = {Cancer research}, volume = {62}, number = {2}, pages = {560-566}, pmid = {11809710}, issn = {0008-5472}, mesh = {Animals ; Breast Neoplasms/*blood supply/pathology/physiopathology ; Carcinoma, Ductal, Breast/*blood supply/pathology/physiopathology ; Contrast Media ; Female ; Hemodynamics/physiology ; Humans ; Magnetic Resonance Angiography ; Mice ; Neoplasm Transplantation ; Neovascularization, Pathologic/*physiopathology ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous ; }, abstract = {In the present study, we examined hemodynamics in vasculogenic mimicry (VM) and angiogenesis of inflammatory breast cancer (IBC) xenografts (WIBC-9), having previously reported on the unique histological features and molecular basis of these processes (K. Shirakawa et al., Cancer Res., 61: 445-451, 2001). Histologically, the WIBC-9 xenografts exhibited invasive ductal carcinoma with a hypervascular structure (angiogenesis) in the tumor margin and VM without endothelial cells, central necrosis, or fibrosis in the tumor center. Results of molecular analysis indicated that WIBC-9 had a vasculogenic phenotype, including expression of Flt-1 and Tie-2. Comparison of WIBC-9 with an established non-IBC xenograft (MC-5), using time-coursed dynamic micromagnetic resonance angiography analysis (with our newly developed intravascular macromolecular magnetic resonance imaging contrast agent), electromicroscopy, and immunohistochemistry, demonstrated blood flow and a VM-angiogenesis junction in the central area of the WIBC-9 tumor. It has previously been considered impossible to prove a connection between VM and angiogenesis using angiography, because there are no intravascular macromolecular magnetic resonance imaging contrast agents that do not exhibit significant leakage through the vascular wall. In the present study, laser-captured microdissection was performed in regions of WIBC-9 tumors that exhibited VM without endothelial cells, central necrosis, or fibrosis, revealing expression of human-Flt-1 and human-Tie2 and the absence of human-CD31, human-endothelin B receptor, and human-thrombin receptor. These facts led us to hypothesize that the VM of WIBC-9 involves hemodynamics that serve to feed WIBC-9 cells, and this in turn suggests a connection between VM and angiogenesis.}, } @article {pmid11808897, year = {2001}, author = {Venugopalan, P and Agarwal, AK and de Bono, D}, title = {Low proportion of familial dilated cardiomyopathy in an arab population with a high prevalence of consanguineous marriages.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {90}, number = {11}, pages = {1267-1270}, doi = {10.1080/080352501317130308}, pmid = {11808897}, issn = {0803-5253}, mesh = {Adolescent ; Adult ; Cardiomyopathy, Dilated/*ethnology/*genetics ; Child ; Child, Preschool ; *Consanguinity ; Female ; Humans ; Infant ; Male ; Middle Aged ; Oman/epidemiology ; Prospective Studies ; Statistics, Nonparametric ; }, abstract = {UNLABELLED: In this study, 770/890 (87%) first-degree relatives from 108 families of hospitalized patients with idiopathic dilated cardiomyopathy (IDC) were screened using clinical examination, electrocardiography and echocardiography. Thirty percent of the patients were born to consanguineous parents. Familial dilated cardiomyopathy (FDC) was found in 7 (6.5%) families, which is lower than the earlier published figures of 20-25%. Patients with IDC were younger at presentation (p = 0.002) and were more often associated with parental consanguinity (p = 0.04). but the survival rates of familial patients did not differ significantly.

CONCLUSION: Despite the high prevalence of consanguinity, there was a low proportion of FDC in the study population. With the prospects of treatment of asymptomatic IDC to slow the progression of the disease, all family members of newly identified IDC patients should receive screening and counselling, with appropriate therapy where indicated.}, } @article {pmid11784211, year = {2001}, author = {Fujioka, S and Kitaura, Y}, title = {Coxsackie B virus infection in idiopathic dilated cardiomyopathy: clinical and pharmacological implications.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {15}, number = {12}, pages = {791-799}, doi = {10.2165/00063030-200115120-00002}, pmid = {11784211}, issn = {1173-8804}, mesh = {Antiviral Agents/*therapeutic use ; Cardiomyopathy, Dilated/*complications/drug therapy/*virology ; *Enterovirus B, Human/genetics ; Enterovirus Infections/*complications/*drug therapy/genetics/virology ; Heart/virology ; Humans ; Treatment Outcome ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC.}, } @article {pmid11781552, year = {2002}, author = {Dagdeviren, B and Akdemir, O and Bolca, O and Eren, M and Gürlertop, Y and Tezel, T}, title = {Myocardial texture analysis in idiopathic dilated cardiomyopathy: prediction of contractile reserve on dobutamine echocardiography.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {15}, number = {1}, pages = {36-42}, doi = {10.1067/mje.2002.115618}, pmid = {11781552}, issn = {0894-7317}, mesh = {Adrenergic beta-Agonists ; Adult ; Aged ; Blood Pressure/drug effects/physiology ; Cardiomyopathy, Dilated/diagnostic imaging/mortality/*pathology ; Dobutamine ; Echocardiography, Stress ; Female ; Follow-Up Studies ; Heart Rate/drug effects/physiology ; Humans ; Male ; Middle Aged ; Myocardial Contraction/drug effects/physiology ; Myocardium/*pathology/*ultrastructure ; Predictive Value of Tests ; ROC Curve ; Sensitivity and Specificity ; Severity of Illness Index ; Stroke Volume/drug effects/physiology ; Survival Analysis ; }, abstract = {Conventional resting echocardiography is not able to predict contractile reserve (CR) of patients with idiopathic dilated cardiomyopathy. The aim of this study was to investigate whether the videodensitometric myocardial texture analysis could predict the CR of these patients. Myocardial texture analysis was performed on echocardiographic digitized images of 27 patients with IDC through a calibrated 256 gray level digitization system. Cyclic variation (CV) index of myocardial mean gray level (MGL) was calculated according to the formula: (MGL(diast) - MGL(syst))/ MGL(diast) x 100. CR was defined as the %-change of ejection fraction by 10 microg/kg per minute dobutamine infusion. A clinical follow-up was also performed for all patients for an average of 8 +/- 3 months. CR ranged from -1.8% to 50.3%. CV index of both septum and posterior wall (PW) was the single parameter significantly correlated to CR (r = 0.69 and r = 0.77, respectively, P <.0001 for both). The mean resting CV index of septum and PW were significantly lower in patients with CR less than 17%-median value of all subjects-(5.7 +/- 5.6 vs 16.9 +/- 7.9 and 5.4 +/- 5.9 vs 16.1 +/- 6.4, respectively, P <.0001 for both). A CV index of 10% for both septum and PW yielded a sensitivity of 77% and 84%, and a specificity of 84% and 84% for predicting diminished CR, respectively. The event-free survival rate was significantly lower in patients with CR less than 17% (61.5% vs 92.8%, P <.05). The CV index of both septum and PW were also significantly lower in patients with cardiac events (13.6 +/- 8 vs 4.3 +/- 6, P <.05 and 14.7 +/- 7 vs 4.1 +/- 7, P <.01, respectively). Ultrasonic myocardial texture analysis in idiopathic dilated cardiomyopathy has a high ability to discriminate the patients with and without preserved CR, and patients with unfavorable outcome as well.}, } @article {pmid11773334, year = {2002}, author = {Voss, A and Baier, V and Schumann, A and Hasart, A and Reinsperger, F and Schirdewan, A and Osterziel, KJ and Leder, U}, title = {Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy.}, journal = {The Journal of physiology}, volume = {538}, number = {Pt 1}, pages = {271-278}, pmid = {11773334}, issn = {0022-3751}, mesh = {Adult ; *Blood Pressure ; Cardiac Complexes, Premature/*complications/*physiopathology ; Cardiomyopathy, Dilated/*complications/*physiopathology ; Electrocardiography ; Female ; *Heart Rate ; Humans ; Male ; Middle Aged ; Reference Values ; }, abstract = {Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non-invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 +/- 32.6 vs. 9.8 +/- 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 +/- 0.60 vs. 2.07 +/- 1.04 mmHg BBI(-1) (BBI, beat-to-beat interval), P < 0.05), as was HR-TS (8.46 +/- 7.90 vs. 30.73 +/- 22.90 ms BBI(-1), P < 0.01). HR-TO was significantly higher in IDC patients (-0.56 +/- 2.19 vs. -5.52 +/- 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC.}, } @article {pmid11770353, year = {2001}, author = {Gursan, N and Karakök, M and Sari, I and Gursan, MS}, title = {The relationship between expression of p53/Bcl-2 and histopathological criteria in breast invasive ductal carcinomas.}, journal = {International journal of clinical practice}, volume = {55}, number = {9}, pages = {589-590}, pmid = {11770353}, issn = {1368-5031}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Tumor Suppressor Protein p53/*analysis ; }, abstract = {Seventy-five cases of invasive ductal carcinoma (IDC) on whom axillary lymph node dissection and mastectomy were performed between 1996 and 2000 were reviewed histopathologically. The slides were stained immunohistologically with p53 and Bcl-2. In 40 cases we observed 53% Bcl-2 and 69% p53 positivity. There were correlations between p53 and tumour grade, and also between p53 and Bcl-2. We did not observe any connection between the main histopathological prognostic factors--lymph node metastasis, tumour size, tubule formation, pleomorphism--and p53/Bcl-2. In our study, IDC with a high mitotic index and poor differentiation showed mutant p53 positive staining. Expression of Bcl-2 is associated with low nuclear grade and absence of mutant p53. This study was designed to reveal the correlation between histopathological findings and the expression of p53/Bcl-2 on prognosis.}, } @article {pmid11756721, year = {2002}, author = {Thurfjell, MG and Lindgren, A and Thurfjell, E}, title = {Nonpalpable breast cancer: mammographic appearance as predictor of histologic type.}, journal = {Radiology}, volume = {222}, number = {1}, pages = {165-170}, doi = {10.1148/radiol.2221001471}, pmid = {11756721}, issn = {0033-8419}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*diagnostic imaging/pathology ; Calcinosis ; Diagnosis, Differential ; Female ; Humans ; Mammography ; Middle Aged ; Odds Ratio ; Palpation ; Predictive Value of Tests ; Retrospective Studies ; }, abstract = {PURPOSE: To investigate the association between mammographic appearance and histologic diagnosis of nonpalpable breast cancers.

MATERIALS AND METHODS: Mammographic characteristics of 317 consecutive clinically nonpalpable breast cancers in patients treated with breast-conserving surgery were reviewed. Malignant lesions were categorized as spiculated masses, other lesions, calcifications, and combined findings. Calcifications were characterized as amorphous, pleomorphic, or fine linear and branching. Logistic regression was used for the evaluation. Odds ratios (ORs) represent the magnitude of the association between a histologic diagnosis and a mammographic finding.

RESULTS: Spiculated mass without calcifications (n = 150) and calcifications alone (n = 79) accounted for three of four cancers. A spiculated mass without calcifications was strongly associated with invasive cancers (OR = 12). Calcifications alone were strongly associated with ductal carcinoma in situ (DCIS) (OR = 19). In a decreasing order, the following invasive cancers were each associated with spiculated lesions without calcifications: ductal carcinoma grade 1 (OR = 28), ductal carcinoma grade 2 (OR = 17), lobular carcinoma (OR = 11), and ductal carcinoma grade 3 (OR = 4.6). Fine linear and branching calcifications alone were associated with not only DCIS nuclear grades 3 (OR = 17) and 2 (OR = 9.7) but also with invasive ductal carcinoma grade 3 (OR = 13).

CONCLUSION: Mammographic appearance can be a predictor of histologic diagnosis in three of four nonpalpable breast cancers.}, } @article {pmid11744991, year = {2002}, author = {Terasaki-Fukuzawa, Y and Kijima, H and Suto, A and Takeshita, T and Iezumi, K and Sato, S and Yoshida, H and Sato, T and Shimbori, M and Shiina, Y}, title = {Decreased nm23 expression, but not Ki-67 labeling index, is significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.}, journal = {International journal of molecular medicine}, volume = {9}, number = {1}, pages = {25-29}, pmid = {11744991}, issn = {1107-3756}, mesh = {Antigens, Nuclear ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary ; Female ; Gene Expression ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/*metabolism ; Lymphatic Metastasis ; Monomeric GTP-Binding Proteins/genetics/*metabolism ; NM23 Nucleoside Diphosphate Kinases ; Nuclear Proteins ; *Nucleoside-Diphosphate Kinase ; Transcription Factors/genetics/*metabolism ; }, abstract = {The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly reduced metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between lymph node status and nm23 immunoreactivity, as well as Ki-67 labeling index (LI), of human breast cancer. Of the 44 breast invasive ductal carcinomas, nm23-diffusely positive expression [nm23(+)] was detected in 17 (38.6%), and focally positive/negative expression [nm23(+/-/-)] in 27 (61.4%) cases. Lymph node metastasis was found at a significantly higher incidence in the nm23(+/-/-) cases (18/27, 66.7%) than in the nm23(+) cases (4/17, 23.5%) (p>0.001). In the lymph node metastasis-positive cases, mean LI of Ki-67 cells was 20.9% at the center of the tumors and 24.0% at the advanced margins. In the lymph node metastasis-negative cases, mean LI of Ki-67 cells was 12.4% at the center of the tumors and 27.2% at the advanced margins. Decrease of nm23 expression, but not Ki-67 LI, was significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.}, } @article {pmid11743329, year = {2002}, author = {Stephan, C and Jung, K and Schnorr, D and Lein, M and Sinha, P and Loening, SA}, title = {Re: a prospective study to evaluate the role of complexed prostate specific antigen and free/total prostate specific antigen ratio for the diagnosis of prostate cancer. I.D.C. Mitchell, B.L. Croal, A. Dickie, N.P. Cohen and I. Ross. J Urol, 165: 1549-1553, 2001.}, journal = {The Journal of urology}, volume = {167}, number = {1}, pages = {259-260}, pmid = {11743329}, issn = {0022-5347}, mesh = {Humans ; Male ; Multicenter Studies as Topic ; Prospective Studies ; Prostate-Specific Antigen/*analysis ; Prostatic Neoplasms/*diagnosis ; ROC Curve ; }, } @article {pmid11741555, year = {2001}, author = {Pratali, L and Picano, E and Otasevic, P and Vigna, C and Palinkas, A and Cortigiani, L and Dodi, C and Bojic, D and Varga, A and Csanady, M and Landi, P}, title = {Prognostic significance of the dobutamine echocardiography test in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {88}, number = {12}, pages = {1374-1378}, doi = {10.1016/s0002-9149(01)02116-6}, pmid = {11741555}, issn = {0002-9149}, mesh = {Aged ; Cardiomyopathy, Dilated/*diagnostic imaging/mortality ; *Echocardiography, Stress ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; ROC Curve ; Survival Rate ; }, abstract = {Dobutamine stress echo provides potentially useful information on idiopathic dilated cardiomyopathy (IDC). From February 1, 1997, to October 1, 1999, 186 patients (131 men and 55 women, mean age 56 +/- 12 years) with IDC, ejection fraction <35%, and angiographically normal coronary arteries were studied by high-dose (up to 40 micro/kg/min) dobutamine echo in 6 centers, all quality controlled for stress echo reading. In all patients, wall motion score index (WMSI) (from 1 = normal to 4 = dyskinetic in a 16- segment model of the left ventricle) was evaluated by echo at baseline and peak dobutamine. One hundred eighty-four patients were followed up (mean 15 +/- 13 months) and only cardiac death was considered as an end point. There were 29 cardiac deaths. Significant parameters for survival prediction at univariate analysis are: DeltaWMSI (chi-square 20.1; p <0.0000), New York Heart Association (NYHA) class (chi-square 17.57; p <0.0000), rest ejection fraction (chi-square 10.41; p = 0.0013), angiotensin-converting enzyme inhibitors (chi-square 8.23; p = 0.0041), and hypertension (chi-square 8.08, p = 0.0045). In the multivariate stepwise analysis only DeltaWMSI and NYHA were independent predictors of outcome (DeltaWMSI = hazard ratio 0.02, p < 0.0000; NYHA class = hazard ratio 3.83, p < 0.0000). Kaplan-Meier survival estimates showed a better outcome for patients with a large inotropic response (DeltaWMSI > or =0.44, a cutoff identified by receiver-operating characteristic curves analysis) than for those with a small or no myocardial inotropic response to dobutamine (93.6% vs 69.4%, p = 0.00033). Thus, in patients with IDC, an extensive contractile reserve identified by high-dose dobutamine stress echocardiography is associated with a better survival.}, } @article {pmid11737309, year = {2001}, author = {Frolik, D and Caduff, R and Varga, Z}, title = {Pleomorphic lobular carcinoma of the breast: its cell kinetics, expression of oncogenes and tumour suppressor genes compared with invasive ductal carcinomas and classical infiltrating lobular carcinomas.}, journal = {Histopathology}, volume = {39}, number = {5}, pages = {503-513}, doi = {10.1046/j.1365-2559.2001.01252.x}, pmid = {11737309}, issn = {0309-0167}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Nuclear ; *Apolipoproteins ; Apolipoproteins D ; Apoptosis ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Carcinoma, Lobular/metabolism/*pathology ; Carrier Proteins/analysis ; Cell Division ; Female ; *Glycoproteins ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Ki-67 Antigen ; *Membrane Transport Proteins ; Middle Aged ; Mucin-1/analysis ; Nuclear Proteins/analysis ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/biosynthesis ; }, abstract = {AIMS: The study addresses whether pleomorphic lobular breast carcinomas represent a distinct entity with respect to proliferation and apoptosis as well the expression of the p53, bcl-2 and Her2 protein.

METHODS AND RESULTS: The study included 30 cases of pleomorphic lobular carcinoma (PLC; G2 n=15, G3 n=15). Poorly differentiated invasive ductal carcinomas (IDC; n=15) and well-differentiated infiltrating lobular carcinomas (ILC; n=15) were used as controls. Lymph node metastases were present equally in all groups. MIB-1 labelling was counted as: PLC (G2) 8.36%; PLC (G3) 11.3%; IDC 44.26%; ILC 2.19% (P=0.0001, P=0.004, P=0.001). Apoptotic index was: PLC (G2) 0.82%; PLC (G3) 1.2%; IDC 2.09%; ILC 0.6% (P=0.009, P=0.001). Over-expression of Her2 protein was detected in 53% of PLC (G3) tumours and was present only in scattered cases in the other groups. PLCs and ILCs were strongly positive for bcl-2 and for hormone receptors, while p53+ cells were rare. IDCs exhibited a heterogeneous staining pattern for bcl-2 and for hormone receptors, while p53+ cells occurred considerably more frequently. Stage could not be linked directly to proliferation or apoptosis.

CONCLUSION: Our data suggest that more frequent over-expression of Her2 among PLCs (G3) as well as the generally low apoptosis can contribute to their aggressive behaviour.}, } @article {pmid11729483, year = {2001}, author = {Chino, Y and Suzuki, Y and Ubukata, N and Yoshihara, K and Tani, T and Ogata, M}, title = {[Hepatic infusion of docetaxel using PEIT for a patient with stage IV breast cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {28}, number = {12}, pages = {1897-1899}, pmid = {11729483}, issn = {0385-0684}, mesh = {Antineoplastic Agents, Phytogenic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*drug therapy/*secondary ; Cyclophosphamide/administration & dosage ; Docetaxel ; Drug Administration Schedule ; Ethanol/administration & dosage ; Fadrozole/administration & dosage ; Female ; Floxuridine/administration & dosage ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Injections, Intralesional ; Liver Neoplasms/*drug therapy/*secondary ; Middle Aged ; Paclitaxel/*analogs & derivatives/*therapeutic use ; *Taxoids ; }, abstract = {Hepatic infusion of docetaxel using PEIT was performed for a patient with stage IV breast cancer. Docetaxel was effective to a solitary liver metastatic lesion. A 64-year-old woman was admitted to our hospital because of a left breast mass that was bleeding. She was diagnosed with stage IV breast cancer. Surgery was performed on February 16th. The pathological diagnosis was invasive ductal carcinoma, and hormone receptors were negative. Two weeks after operation, monthly docetaxel injections were given together with doxifluidine 400 mg/day p.o., cyclophosphamide 50 mg/day p.o., and fadrozole hydrochloride hydrate 2 mg/day p.o. After two courses, hepatic infusion of docetaxel was performed using PEIT after informed consent. The patient's high serum CEA and CA15-3 level returned to the normal range. A metastatic lesion on CT changed to a cystic pattern. These results suggest that PEIT is worth trying in patients with solitary liver metastasis from breast cancer.}, } @article {pmid11726136, year = {2001}, author = {Spisek, R and Bretaudeau, L and Barbieux, I and Meflah, K and Gregoire, M}, title = {Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {50}, number = {8}, pages = {417-427}, doi = {10.1007/s002620100215}, pmid = {11726136}, issn = {0340-7004}, mesh = {Apoptosis ; Cell Culture Techniques/*methods ; Cell Differentiation ; Cell Division ; Cell Survival ; Cells, Cultured/cytology/drug effects/metabolism ; Dendritic Cells/*cytology/drug effects/metabolism ; Dinoprostone/pharmacology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Hemocyanins/immunology ; Humans ; Immunophenotyping ; Interleukin-1/pharmacology ; Interleukin-12/chemistry/*metabolism ; Interleukin-13/pharmacology ; Interleukin-6/pharmacology ; Lymphocyte Culture Test, Mixed ; Melanoma/pathology ; Phagocytosis ; Poly I-C/pharmacology ; Protein Structure, Tertiary ; Recombinant Proteins/pharmacology ; Reproducibility of Results ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {Dendritic cells (DC) have been shown to be efficient antigen-presenting cells (APC) and, as such, could be considered ideal candidates for cancer immunotherapy. Immature DC (iDC) efficiently capture surrounding antigens; however, only mature DC (mDC) prime naive T lymphocytes. Clinical trials using DC-based tumor vaccines have achieved encouraging, but limited, success, possibly due to the use of immature or incompletely mature DC. Thus, it was apparent that a method capable of generating large numbers of fully functional iDC, their pulsing with desired form of tumor antigens and the subsequent complete and reproducible maturation of iDC is needed. Therefore, we compared two different methods of producing large numbers of iDC. Both protocols yielded comparable numbers of cells with an iDC phenotype with phagocytic function. We next determined which of the clinically applicable activators could induce the complete and reproducible maturation of DC, in order to define the most suitable combination for future clinical trials. Only a combination of TNFalpha + Poly (I:C), or a previously described cytokine cocktail of TNFalpha + IL-1beta + IL-6 + prostaglandin E2, induced the complete activation of the whole DC population, as assessed by the cell surface expression of CD83 and costimulatory molecules. The matured DC were functionally superior to iDC in their ability to stimulate the proliferation of allogeneic lymphocytes and autologous keyhole limpet hemocyanin (KLH)-specific T lymphocytes. Furthermore, only the combination of TNFalpha + Poly (L:C) activated DC to produce large amounts of biologically active p70 IL-12. Thus DC maturation by TNFalpha + Poly (I:C) could efficiently bias T cell response towards Th1 response. Implementation of our results into clinical protocols used for DC generation could be beneficial for future immunotherapy trials.}, } @article {pmid11721699, year = {2001}, author = {Matera, L and Mori, M and Galetto, A}, title = {Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells.}, journal = {Lupus}, volume = {10}, number = {10}, pages = {728-734}, doi = {10.1191/096120301717164967}, pmid = {11721699}, issn = {0961-2033}, mesh = {Animals ; *Antigen Presentation/drug effects ; Antigens, Surface/immunology ; Autoimmunity/immunology ; *Cell Differentiation ; Dendritic Cells/*cytology/drug effects/*immunology ; Humans ; Monocytes/*cytology ; Prolactin/*immunology/pharmacology ; Stem Cells/*cytology ; }, abstract = {Monocyte derived macrophages (Mphi) and dendritic cells (DC) play critical roles at the interface between innate and adaptive immunity. Both types of cells can effectively phagocytose exogenous antigens, whereas only DC can process and present them efficiently to antigen-specific T lymphocytes. The hormone PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine--immune loop and a local regulator of lymphocyte response. Its main feature is cooperation with cytokines and hemopoietins. Triggering of monocyte PRL receptors with physiological-to-supraphysiological concentrations of PRL up-regulates the GM-CSF receptors, resulting in synergistic PRL-GM-CSF induced maturation of immature (i)DC. Further incubation induces increased antigen-presenting activity at the highest PRL concentrations studied (200 ng/ml). IFN-gamma, release by allogeneic lymphocytes is dependent on T cell-triggered IL-12 release by PRL-preincubated iDC. This, in turn, may be secondary to increased DC expression of CD40 or IFN-gamma. The permissive action of high PRL concentrations in the antigen presenting process may be of significance in initiation of the response against major histocompatibility complex (MHC)-presented self-antigens and may explain the association of hyperprolactinemia with autoimmune diseases.}, } @article {pmid11706082, year = {2001}, author = {Wang, X and Mori, I and Tang, W and Yang, Q and Nakamura, M and Nakamura, Y and Sato, M and Sakurai, T and Kennichi, K}, title = {Metaplastic carcinoma of the breast: p53 analysis identified the same point mutation in the three histologic components.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {11}, pages = {1183-1186}, doi = {10.1038/modpathol.3880456}, pmid = {11706082}, issn = {0893-3952}, mesh = {Base Sequence ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Squamous Cell/genetics/metabolism/*pathology ; Chondrosarcoma/genetics/metabolism/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/chemistry/genetics ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Metaplasia ; Middle Aged ; Point Mutation ; Tumor Suppressor Protein p53/analysis/genetics ; }, abstract = {A rare case of metaplastic carcinoma of the breast with both squamous metaplasia and cartilaginous metaplasia was reported. Histologically, the neoplasm revealed complex features, which were consisting of invasive ductal carcinoma, squamous carcinomatous component and chondrosarcomatoid component. Gradual transition of each component was recognized microscopically. p53 mutation analysis disclosed the same point mutation in three histologically different components, but not in the normal epithelium. Based on the morphologic findings, immunohistochemical findings and the p53 mutation analysis, we concluded that these three components in the tumor originated from the same duct progenitor cells.}, } @article {pmid11706057, year = {2001}, author = {Nielsen, BS and Sehested, M and Duun, S and Rank, F and Timshel, S and Rygaard, J and Johnsen, M and Danø, K}, title = {Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {81}, number = {11}, pages = {1485-1501}, doi = {10.1038/labinvest.3780363}, pmid = {11706057}, issn = {0023-6837}, mesh = {Antibody Specificity ; Biomarkers, Tumor ; Breast Neoplasms/enzymology/*pathology ; Carcinoma, Ductal, Breast/enzymology/*pathology ; Detergents ; Enzyme-Linked Immunosorbent Assay ; Female ; Fixatives ; Fluorescent Antibody Technique ; Formaldehyde ; Humans ; In Situ Hybridization ; Octoxynol ; Paraffin Embedding ; RNA, Messenger/analysis ; Stromal Cells/*enzymology ; Trypsin ; Urokinase-Type Plasminogen Activator/*analysis/genetics/immunology ; }, abstract = {Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix, and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is highly expressed by myofibroblasts surrounding invasively growing cancer cells. However, the localization of uPA protein has not been settled in the published literature. Because uPA is a secreted molecule, it could conceivably be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal carcinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts and macrophages in all cases examined. Additionally, in approximately half of the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 cases, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cells, which thus play a major role in generation of proteolytic activity in ductal breast cancer.}, } @article {pmid11704912, year = {2001}, author = {Bock, K and Iwinska-Zelder, J and Duda, VF and Bonwetsch, C and Rode, G and Hadji, P and Klose, KJ and Schulz, KD}, title = {[Validity of the breast imaging reporting and data system BI-RADS(TM) for clinical mammography in men].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {173}, number = {11}, pages = {1019-1024}, doi = {10.1055/s-2001-18316}, pmid = {11704912}, issn = {1438-9029}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*diagnostic imaging ; Carcinoma in Situ/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging ; Female ; Gynecomastia/*diagnostic imaging ; Humans ; Leiomyosarcoma/*diagnostic imaging ; Male ; *Mammography/classification ; Middle Aged ; Retrospective Studies ; Sex Factors ; Terminology as Topic ; }, abstract = {AIM: The implementation of diagnostic standards enhances quality assurance. The American College of Radiology's Breast Imaging-Reporting and Data System (BI-RADS(TM)) is intended to standardize terminology in the mammography report, the assessment of the findings, and the recommendation af action to be taken. The purpose of this study was to assess the value of the standardized system for clinically apparent male breast tumors. Do the special male anatomy and physiology limit the applicability of an evaluation system designed for female screening mammograms?

METHODS: 4 investigators with different degrees of experience retrospectively evaluated 160 male mammograms. Our study was based on the 36 cases which could be correlated to histopathological findings: gynecomastia in the majority of cases, but also 4 invasive ductal carcinoma, 1 leiomyosarcoma and 1 ductal carcinoma in situ.

RESULTS: Assessment of the mammograms by BI-RADS(TM) (3(rd) Edition 1998) correctly placed all cases of malignancy into categories 4 and 5 without respect to the investigators's level of experience.

CONCLUSION: Therefore, we conclude that the BI-RADS(TM)-classification can successfully be used to classify male mammograms with a high positive predictive value for malignancy. Knowledge of gender-specific imaging characteristics increases the specificity at a constant high level of sensitivity.}, } @article {pmid11704911, year = {2001}, author = {Partik, B and Mallek, R and Rudas, M and Pokieser, P and Wunderbaldinger, P and Helbich, TH}, title = {[Malignant and benign diseases of the breast in 41 male patients: mammography, sonography and pathohistological correlations].}, journal = {RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin}, volume = {173}, number = {11}, pages = {1012-1018}, doi = {10.1055/s-2001-18336}, pmid = {11704911}, issn = {1438-9029}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms, Male/*diagnosis/diagnostic imaging ; Carcinoma in Situ/*diagnosis/diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnosis/diagnostic imaging ; Diagnosis, Differential ; Gynecomastia/*diagnosis/diagnostic imaging ; Humans ; Male ; *Mammography ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; *Ultrasonography, Mammary ; }, abstract = {AIM: The goal of our study was to evaluate findings in mammography and sonography in male patients with pathohistologically proven diseases of the breast.

MATERIAL AND METHODS: Mammographies and sonographies, which were obtained in 41 male patients in a 6-year period, were retrospectively evaluated in accordance with the BI-RADS(R) classification.

RESULTS: Histologically 13 carcinomas, 21 gynecomastias, 3 pseudogynecomastias, 2 epithelial inclusion cysts and 2 other benign lesions were diagnosed. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mammography in differentiation of benign versus malignant disease were 92 %, 89 %, 80 %, 96 % and 90 %, respectively. Additional sonography did not change these results. However, sonography increased diagnostic confidence in 18.2 % (2/11) of suspicious lesions.

CONCLUSION: In our study the invasive ductal carcinoma of male patients was a predominantly lobulated, ill-defined lesion in mammography and sonography. The differentiation of carcinoma to pseudogynecomastia and diffuse or dendritic gynecomastia was securely feasible. However, we could not reliably distinguish between carcinoma and some benign mass lesions. In cases of mammographically diagnosed masses or unclear mammography, additional sonography should be performed to increase the diagnostic confidence.}, } @article {pmid11694790, year = {2001}, author = {Ménard, S and Fortis, S and Castiglioni, F and Agresti, R and Balsari, A}, title = {HER2 as a prognostic factor in breast cancer.}, journal = {Oncology}, volume = {61 Suppl 2}, number = {}, pages = {67-72}, doi = {10.1159/000055404}, pmid = {11694790}, issn = {0030-2414}, mesh = {Adult ; Age of Onset ; Aged ; Biomarkers, Tumor/*analysis ; Breast/chemistry/pathology ; Breast Neoplasms/*chemistry/classification/genetics/mortality/pathology ; Carcinoma, Ductal, Breast/chemistry/genetics/mortality/pathology ; Carcinoma, Intraductal, Noninfiltrating/chemistry/genetics/pathology ; Cell Transformation, Neoplastic/genetics ; Diagnostic Tests, Routine ; Disease Progression ; Estrogens ; Female ; Genes, bcl-2 ; Genes, erbB-2 ; Genes, p53 ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating ; Middle Aged ; Mitotic Index ; Models, Biological ; Necrosis ; Neoplasm Invasiveness ; Neoplasm Proteins/*analysis ; Neoplasms, Hormone-Dependent/chemistry/genetics/mortality/pathology ; Phenotype ; Precancerous Conditions/metabolism/pathology ; Prognosis ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Risk Factors ; }, abstract = {HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. HER2-positive tumors also contain p53 abnormalities, tend to be hormone receptor and bcl-2 negative, have lymphoid infiltration (LI) and a high mitotic index. Patients with LI who are HER2 positive have a better prognosis than those who are HER2 negative, whereas HER2-positive patients without LI have a significantly worse prognosis than HER2-negative patients. Morphological and biological alterations appear to identify two categories of breast tumor. Two hypotheses may explain the progression to two tumor types: (1) atypical ductal hyperplasia (ADH) is a precursor of ductal carcinoma in situ (DCIS), which is a precursor of invasive ductal carcinoma (IDC); or (2) ADH is a precursor of HER2-negative IDC whereas DCIS is a precursor of HER2-positive IDC. The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.}, } @article {pmid11694076, year = {2001}, author = {Enomoto, M and Nagayama, H and Takahashi, TA}, title = {Enhancement of migratory and aggregate activities of human peripheral blood monocyte-derived dendritic cells by stimulation with RANTES.}, journal = {Microbiology and immunology}, volume = {45}, number = {9}, pages = {639-647}, doi = {10.1111/j.1348-0421.2001.tb01297.x}, pmid = {11694076}, issn = {0385-5600}, mesh = {Cell Movement ; Chemokine CCL5/analysis/genetics/*immunology ; Dendritic Cells/*immunology ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukocytes, Mononuclear/*immunology ; Lymphocyte Activation ; Polymerase Chain Reaction ; RNA, Messenger/analysis ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {We examined the effects of various chemokines on the functional activation of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4)-generated human peripheral blood monocyte-derived immature dendritic cells (iDC). Stimulation of iDC with regulated on activation normal T cell expressed and secreted (RANTES) resulted in the promotion of their chemotactic migratory capacity in response to RANTES when compared with that of unstimulated cells. TNF-alpha induced a homotypic aggregated cluster formation of iDC in a dose-dependent manner, whereas the combination of TNF-alpha and RANTES exhibited more potent induction. IDC stimulated with RANTES were more efficient than unstimulated iDC in the production of endogenous RANTES. Treatment of iDC with the combination of TNF-alpha and RANTES was just little effective for the enhancement of allogeneic T-cell stimulatory capacity as compared with that of TNF-alpha treated iDC. These results suggest that endogenous secretions of RANTES from iDC stimulated with RANTES be potentially involved in RANTES-induced changes of properties with respect to morphology and function.}, } @article {pmid11692213, year = {2001}, author = {de Leeuw, N and Ruiter, DJ and Balk, AH and de Jonge, N and Melchers, WJ and Galama, JM}, title = {Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy.}, journal = {Transplant international : official journal of the European Society for Organ Transplantation}, volume = {14}, number = {5}, pages = {299-306}, doi = {10.1007/s001470100339}, pmid = {11692213}, issn = {0934-0874}, mesh = {Adult ; CD8-Positive T-Lymphocytes/immunology/pathology ; Cardiomyopathy, Dilated/*pathology ; Cell Nucleus/pathology/ultrastructure ; Female ; Heart Transplantation/*physiology ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Inflammation/immunology/pathology ; Myocardium/immunology/*pathology/ultrastructure ; Patient Selection ; T-Lymphocytes/immunology/pathology ; }, abstract = {Explanted hearts were examined to determine whether specific histopathologic features are present in the myocardium of patients with end-stage idiopathic dilated cardiomyopathy (IDC). Extensive histopathologic examination by light microscopy, electron microscopy and immunohistochemistry revealed marked fibrosis in the hearts of 21 of 37 IDC patients and in 26 of 35 patients with heart diseases of known causes. Reactive (interstitial and perivascular) fibrosis predominated in the IDC hearts, whereas both reparative (replacement) fibrosis and reactive fibrosis were found in the comparison group. Endocardial fibroelastosis was found in nine patients with IDC and in 14 patients from the comparison group. Distinct patterns of fibrosis were the sole significant histopathologic difference between myocardial samples from patients with IDC and from those with heart diseases of known causes. The diffuse presence of reactive fibrosis in IDC patients suggests a more generalised dysfunction that affects the composition of the myocardial extracellular matrix.}, } @article {pmid11673063, year = {2001}, author = {Mehrabi, MR and Serbecic, N and Ekmekcioglu, C and Tamaddon, F and Ullrich, R and Sinzinger, H and Glogar, HD}, title = {The isoprostane 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human heart valves.}, journal = {Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology}, volume = {10}, number = {5}, pages = {241-245}, doi = {10.1016/s1054-8807(01)00084-9}, pmid = {11673063}, issn = {1054-8807}, mesh = {Adult ; Aged ; Aortic Valve/*metabolism/*pathology ; Biomarkers ; Cardiomyopathies/*metabolism/*pathology ; Dinoprost/*analogs & derivatives/*metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; *Oxidative Stress ; Pulmonary Valve/*metabolism/*pathology ; Radioimmunoassay ; Risk Factors ; }, abstract = {To date, little information is available concerning oxidative injury in human cardiac valves. Therefore, we sought to investigate whether the isoprostane, 8-epi-PGF(2alpha), a novel oxidative stress marker, is localized in aortic and pulmonary valves derived from explanted hearts of patients suffering from idiopathic dilative cardiomyopathy (IDC). By using semiquantitative immunohistochemistry, we demonstrated that 8-epi-PGF(2alpha) is localized in both valves with pulmonary valves accumulating more of this isoprostane compared to aortic valves (36.69+/-12.04% vs. 31.54+/-11.49%, P<.05). These results were confirmed by a radioimmunoassay (RIA) analysis showing a similar, but not significant, difference between the two valves (288.50+/-72.18 pg/mg protein in the pulmonary valves and 267.30+/-58.77 pg/mg protein in aortic valves, P=.09). Considering the data presented in this study, we suggest that 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human semilunar valves.}, } @article {pmid11665790, year = {2001}, author = {Baba, A and Yoshikawa, T and Chino, M and Murayama, A and Mitani, K and Nakagawa, S and Fujii, I and Shimada, M and Akaishi, M and Iwanaga, S and Asakura, Y and Fukuda, K and Mitamura, H and Ogawa, S and , }, title = {Characterization of anti-myocardial autoantibodies in Japanese patients with dilated cardiomyopathy.}, journal = {Japanese circulation journal}, volume = {65}, number = {10}, pages = {867-873}, doi = {10.1253/jcj.65.867}, pmid = {11665790}, issn = {0047-1828}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Autoantibodies/*analysis ; Cardiomyopathy, Dilated/etiology/*immunology ; Case-Control Studies ; Female ; Humans ; Immunoblotting ; Immunohistochemistry ; Japan ; Male ; Middle Aged ; Myocardium/*immunology ; Odds Ratio ; Tachycardia, Ventricular/immunology ; }, abstract = {Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.}, } @article {pmid11597324, year = {2001}, author = {Unger, MA and Rishi, M and Clemmer, VB and Hartman, JL and Keiper, EA and Greshock, JD and Chodosh, LA and Liebman, MN and Weber, BL}, title = {Characterization of adjacent breast tumors using oligonucleotide microarrays.}, journal = {Breast cancer research : BCR}, volume = {3}, number = {5}, pages = {336-341}, pmid = {11597324}, issn = {1465-5411}, mesh = {Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Diagnosis, Differential ; Female ; Gene Expression Profiling ; Humans ; Neoplasms, Second Primary/genetics/*pathology ; Oligonucleotide Array Sequence Analysis ; RNA, Neoplasm/*genetics ; }, abstract = {BACKGROUND: Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles.

METHOD: Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics.

RESULTS: The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710.

CONCLUSION: Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making.}, } @article {pmid11578285, year = {2001}, author = {Crombie, N and Rampaul, RS and Pinder, SE and Elston, CW and Robertson, JF and Ellis, IO}, title = {Extent of ductal carcinoma in situ within and surrounding invasive primary breast carcinoma.}, journal = {The British journal of surgery}, volume = {88}, number = {10}, pages = {1324-1329}, doi = {10.1046/j.0007-1323.2001.01928.x}, pmid = {11578285}, issn = {0007-1323}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/*pathology/radiotherapy/surgery ; Female ; Humans ; Mastectomy/methods ; Middle Aged ; Neoplasm Recurrence, Local/pathology/prevention & control ; Neoplasms, Multiple Primary/*pathology/radiotherapy/surgery ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the pathological and morphological features of ductal carcinoma in situ (DCIS) within and surrounding invasive ductal carcinoma, and to investigate its relationship with clinical outcome and established prognostic variables.

METHODS: One hundred and seven patients with primary operable invasive breast carcinoma and associated DCIS treated by simple or subcutaneous mastectomy or wide local excision with radiotherapy were assessed. Those with pure DCIS and insufficient tumour available for examination were excluded. The most representative haematoxylin and eosin-stained sections from the remaining 91 samples were selected and examined at x 100 magnification using a 45-point, 2-mm grid graticule. The entire section was assessed and the cell under each point of the graticule was classed as either normal (a), DCIS surrounded by normal tissue (b), invasive tumour (c) or DCIS surrounded by invasive malignancy (d). The volume ratio of DCIS in the normal (b/(a + b)) and invasive (d/(c + d)) tissue was then calculated.

RESULTS: The DCIS volume within invasive tumour was not associated with outcome. The DCIS volume within adjacent normal tissue, however, was associated with local recurrence (P = 0.025), disease-free interval (P = 0.048), the occurrence of distant metastases (P = 0.019), death (P = 0.049) and disease-free survival (P = 0.048). Volume ratios of DCIS in normal and invasive tissue were not related to known prognostic factors including lymph node stage, grade, tumour size, vascular invasion or patient age.

CONCLUSION: There is a significant prognostic effect relating to the extent of DCIS associated with an invasive cancer, particularly with respect to local recurrence of tumour. This effect is restricted to the volume of DCIS in the tissue surrounding the invasive lesion rather than the intratumoral component.}, } @article {pmid11569926, year = {2001}, author = {Skálová, A and Stárek, and Kucerová, V and Szépe, P and Plank, L}, title = {Salivary duct carcinoma--a highly aggressive salivary gland tumor with HER-2/neu oncoprotein overexpression.}, journal = {Pathology, research and practice}, volume = {197}, number = {9}, pages = {621-626}, doi = {10.1078/0344-0338-00136}, pmid = {11569926}, issn = {0344-0338}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antigens, Nuclear ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Cell Count ; Female ; Humans ; Immunoenzyme Techniques ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nuclear Proteins/analysis ; Proto-Oncogene Mas ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/analysis/*biosynthesis ; Salivary Gland Neoplasms/*metabolism/pathology/therapy ; Trastuzumab ; }, abstract = {Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.}, } @article {pmid11562768, year = {2001}, author = {Hoang, MP and Callender, DL and Sola Gallego, JJ and Huang, Z and Sneige, N and Luna, MA and Batsakis, JG and El-Naggar, AK}, title = {Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma.}, journal = {International journal of oncology}, volume = {19}, number = {4}, pages = {865-871}, doi = {10.3892/ijo.19.4.865}, pmid = {11562768}, issn = {1019-6439}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; Chromosome Aberrations ; DNA, Neoplasm/*analysis ; Female ; Flow Cytometry ; Humans ; Immunoenzyme Techniques ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Receptors, Androgen/analysis ; Salivary Gland Neoplasms/*chemistry/genetics/pathology ; Tumor Suppressor Protein p53/analysis ; }, abstract = {Salivary duct carcinoma (SDC) is a rare high-grade aggressive neoplasm that manifests close histologic features with invasive ductal carcinoma of the breast (IDC). In contrast to SDC, extensive molecular studies have been performed on IDC and led to the identification of certain biological markers. To investigate the underlying molecular and biologic characteristics of SDC, we performed molecular analyses using microsatellite markers on chromosomal arms 6q, 16q, 17p, and 17q, DNA flow cytometry and immunohistochemical staining for androgen receptor (AR) and p53 expression on 28 examples of these tumors in comparison to 24 IDC cases. Our results show that generally similar allelic alterations, elevated p53 and androgen receptor expressions, and high frequency of DNA aneuploidy are manifested in both SDCs and IDCs. Differences at certain markers on 6q, 17p and 17q chromosomal loci, however, were observed between the two entities. Certain loci on 6q were more frequently altered in SDC than IDC which loci on chromosomes 17p and q arms were more seen in IDCs than SDCs. The majority of SDCs had high AR expression while most of IDCs were AR negative. Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.}, } @article {pmid11561770, year = {2001}, author = {Kollara, A and Kahn, HJ and Marks, A and Brown, TJ}, title = {Loss of androgen receptor associated protein 70 (ARA70) expression in a subset of HER2-positive breast cancers.}, journal = {Breast cancer research and treatment}, volume = {67}, number = {3}, pages = {245-253}, doi = {10.1023/a:1017938608460}, pmid = {11561770}, issn = {0167-6806}, mesh = {Biopsy ; Blotting, Western ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; *Cell Division ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Nuclear Receptor Coactivators ; *Oncogene Proteins ; Phosphorylation ; Receptors, Androgen/*biosynthesis/metabolism ; Signal Transduction ; Trans-Activators/*biosynthesis/metabolism ; *Transcription Factors ; Transfection ; Tumor Cells, Cultured ; }, abstract = {Co-transfection studies indicate that HER2 (erbB-2) overexpression results in the phosphorylation and enhanced transcriptional activity of the androgen receptor (AR). This amplification of AR action is further enhanced by the expression of ARA70, a putative co-activator with a predilection for the AR. Because androgens inhibit the growth of breast cancer cells whereas HER2 overexpression stimulates the growth of these cells, it seems possible that loss of expression of AR or ARA70 in some HER2 overexpressing tumors might confer a growth advantage to these cells. We examined ARA70 and AR expression in 20 HER2-positive (overexpressing) and 21 HER2-negative cases of breast invasive ductal carcinoma (IDC) to determine the relationship between loss of ARA70 and/or AR with HER2 overexpression. Strong ARA70 immunostaining was observed in all normal and breast epithelial cells in fibrocystic change and in in situ carcinoma present in the patient samples. Of the 41 cases of IDC, focal or complete loss of ARA70 protein expression was observed in 46% of the cases, with 60% of HER2-positive versus 33% of HER2-negative cases showing loss. Loss of AR expression was observed in 60% of HER2-positive versus 43% of HER2-negative cases. Remarkably, only 20% of HER2-positive tumors expressed both AR and ARA70, while 43% of HER2-negative tumors expressed both of these elements of the AR signaling pathway. This trend is consistent with a possible clinical relevance of the potential crosstalk between the HER2 and AR signaling pathways. Western blot analysis for ARA70 expression performed on frozen breast biopsies of normal or malignant breast tissue from four patients revealed a 70 kDa immunoreactive band in all four normal tissue samples, with an additional 35 kDa band in two of the breast cancer samples and in human breast cancer MCF-7 cells. This may reflect aberrant splicing in some breast cancers, leading to the emergence of the 35 kDa isoform.}, } @article {pmid11557778, year = {2001}, author = {Nassar, H and Wallis, T and Andea, A and Dey, J and Adsay, V and Visscher, D}, title = {Clinicopathologic analysis of invasive micropapillary differentiation in breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {9}, pages = {836-841}, doi = {10.1038/modpathol.3880399}, pmid = {11557778}, issn = {0893-3952}, mesh = {Aged ; Breast Neoplasms/*pathology ; Carcinoma, Papillary/*pathology ; Cell Differentiation ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Survival Analysis ; }, abstract = {Invasive micropapillary carcinoma (IMPCa) of breast is histologically characterized by growth of cohesive tumor cell clusters within prominent clear spaces resembling dilated angiolymphatic vessels. In this study, eighty three breast carcinomas with IMPCa differentiation were identified by review of the invasive carcinoma cases in our institution and correlated retrospectively with standard clinicopathologic parameters and survival status relative to a control series of cases (mean follow up 7 years). IMPCa growth pattern was present in 6% of all breast carcinomas; it was generally a focal component in otherwise typical invasive ductal carcinoma. It comprised more than 80% of the total neoplasm in only 10 cases (12%), 50-80% of the neoplasm in 7 cases (8%), 20-50% of the neoplasm in 22 cases (26%) and less than 20% in 44 cases (53%). The mean tumor size was 4 cm, 22% invaded skin, and 58% were poorly differentiated, but 71% were ER positive. Axillary node metastases were present in 77% of cases, were typically multiple (51% had three or more positive), and usually contained an IMPCa component (81% of the cases). There was no significant difference in node status, ER status, size, tumor grade, or peritumoral angiolymphatic invasion between tumors with predominant (more than 50%) v/s focal IMPCa components. In both groups 46% of the patients died from their disease (mean interval to death = 36m). Skin involvement and nodal status were the only parameters which predicted poor survival (P =.01). The outcome of patients with IMPCa did not differ significantly from infiltrating ductal carcinomas of similar node status. In conclusion, our results suggest that IMPCa growth pattern may be a manifestation of aggressive behavior, as shown by frequent skin invasion and extensive nodal involvement. However, clinicopathologic features and outcome of IMPCa are not strongly dependent on the relative amount of micropapillary component.}, } @article {pmid11556937, year = {2001}, author = {Keitz, SA and Box, TL and Homan, RK and Bartlett, JA and Oddone, EZ}, title = {Primary care for patients infected with human immunodeficiency virus: a randomized controlled trial.}, journal = {Journal of general internal medicine}, volume = {16}, number = {9}, pages = {573-582}, pmid = {11556937}, issn = {0884-8734}, mesh = {Continuity of Patient Care/organization & administration ; Family Practice/*education ; Female ; HIV Infections/economics/*therapy ; Hospitals, University ; Humans ; Male ; *Medicine ; North Carolina ; *Outcome and Process Assessment, Health Care ; Outpatient Clinics, Hospital/*statistics & numerical data ; Practice Patterns, Physicians'/*statistics & numerical data ; Primary Health Care/*statistics & numerical data ; Prospective Studies ; Quality of Life ; *Specialization ; Utilization Review ; }, abstract = {OBJECTIVE: To measure the impact of a teaching intervention and to compare process and outcomes of care for HIV-infected patients randomly assigned to a general medicine clinic (GMC) or an infectious disease clinic (IDC) for primary care.

DESIGN: Prospective, randomized, controlled trial.

SETTING: University hospital in Durham, NC.

PATIENTS: Two hundred fourteen consecutive HIV-infected patients presenting for primary care.

INTERVENTION: Physicians at the GMC received HIV-related training and evidence-based practice guidelines.

MEASUREMENTS: Utilization of services, health-related quality of life, preventive and screening measures, and antiretroviral use for one year.

RESULTS: At baseline GMC patients were more likely to be African American (85% vs 71%; P =.03) and had lower baseline CD4+ cell counts than IDC patients (262 +/- 269 vs 329 +/- 275; P =.05). A similar and high proportion of patients in both groups received appropriate preventive care services including Pneumocystis carinii pneumonia (PCP) prophylaxis, pneumococcal vaccination, and antiretroviral therapy. Screening for TB was more frequent in GMC (89% vs 68%; P =.001). In the year following randomization, GMC patients made more visits to the emergency department than IDC patients (1.6 +/- 3.0 vs 0.7 +/- 1.5; P =.05). Hospital use was higher for GMC patients with average length of stay 7.8 +/- 6.3 days compared to 5.7 +/- 3.8 days for IDC patients (P =.01). In analyses, which adjust for potential baseline imbalances, these differences remained.

CONCLUSIONS: Targeted education in GMC achieved similar provision of primary care for GMC patients, yet use of health care services was higher for this group. The delivery of adequate primary care is necessary but not sufficient to produce changes in health care utilization.}, } @article {pmid11523929, year = {2001}, author = {Zheng, WQ and Looi, LM and Cheah, PL}, title = {A comparison of the patterns of laminin expression in fibroadenoma, fibrocystic diseases, pre-invasive and invasive ductal breast carcinoma.}, journal = {Pathology}, volume = {33}, number = {3}, pages = {303-306}, pmid = {11523929}, issn = {0031-3025}, mesh = {Basement Membrane/chemistry/metabolism/pathology ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Female ; Fibroadenoma/chemistry/*metabolism/pathology ; Fibrocystic Breast Disease/chemistry/*metabolism/pathology ; Humans ; Immunoenzyme Techniques ; Laminin/analysis/*biosynthesis ; Middle Aged ; Neoplasm Staging ; }, abstract = {The basement membrane (BM), of which laminin is a major glycoprotein component, is an important barrier to tumour cells which must be breeched before metastatic spread can occur. We have compared the pattern of laminin expression in a range of benign and malignant breast lesions to better understand the process of tumour progression. A total of 162 cases of breast samples, comprising 18 fibroadenomas, 22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26 carcinomas with intraductal components, were evaluated for laminin expression by a standard immunoperoxidase method on formalin-fixed, paraffin-embedded histological sections, using a commercial antibody against human laminin. The pattern of laminin expression was charted as follows: Type I, > 70% of BM complete/continuous; Type II, > 70% of BM moderately disrupted; Type III, > 70% of BM completely disrupted. The Type I pattern was observed in all cases of fibroadenoma and fibrocystic diseases, and in 77% of intraductal carcinoma components. Various patterns of BM disruption were observed in invasive ductal carcinoma. Severity of BM disruption correlated with histological grade of the carcinomas (P < 0.001). Small-sized tumours, those without lymphatic invasion and lymph node-negative tumours showed more complete patterns of laminin expression. The current study suggests that tumour cells with high histological grade possess an enhanced capacity to disrupt the basement membrane, an important step in the metastatic process. The detection of BM disruption by immunohistochemical staining for laminin is technically easy and may be usefully applied for the differentiation of in situ and microinvasive carcinoma.}, } @article {pmid11521228, year = {2001}, author = {Fukushima, N and Sakamoto, M and Mukai, K and Kanai, Y and Shimada, K and Kosuge, T and Hirohashi, S}, title = {Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.}, journal = {Human pathology}, volume = {32}, number = {8}, pages = {834-841}, doi = {10.1053/hupa.2001.26473}, pmid = {11521228}, issn = {0046-8177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/classification/mortality/*pathology/surgery ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/classification/mortality/*pathology/surgery ; Proportional Hazards Models ; Survival Rate ; }, abstract = {Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.}, } @article {pmid11500791, year = {2001}, author = {Giannotti Filho, O and Miiji, LN and Vainchenker, M and Gordan, AN}, title = {Breast cancer with choriocarcinomatous and neuroendocrine features.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {119}, number = {4}, pages = {154-155}, doi = {10.1590/s1516-31802001000400009}, pmid = {11500791}, issn = {1516-3180}, mesh = {Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/*pathology ; Choriocarcinoma/chemistry/*pathology ; Chorionic Gonadotropin/analysis ; Chorionic Gonadotropin, beta Subunit, Human/analysis ; Female ; Humans ; Middle Aged ; }, abstract = {CONTEXT: Breast cancer may express the presence of b-human chorionic gonadotrophin in 12% to 18% of cases, using immunohistochemical reactions. Usually the tumors will show positivity in a few scattered cells. Breast cancer with choriocarcinomatous features, as reported by Saigo and Rosen, is a distinct variant of breast cancer. We report a case of breast cancer with choriocarcinomatous and neuroendocrine features.

OBJECTIVE: This is a case report of an invasive ductal carcinoma of the breast with choriocarcinomatous and neuroendocrine features.

DESIGN: Case Report.

CASE REPORT: A 50-year-old Brazilian woman underwent surgery for a lump in the right breast, which had been first noticed about 3 months earlier. The surgery consisted of quadrantectomy followed by right mastectomy with ipsilateral axillary lymph node dissection. The specimen from the quadrantectomy revealed a 7 x 6.5 x 4.5 cm tumor. Histology of the lesion showed the presence of an invasive ductal carcinoma with areas of giant cells and intense atypia. The immunohistochemistry was positive in the pleomorphic areas for human chorionic gonadotrophin, while the less pleomorphic areas showed positivity for synaptophysin and chromogranin.}, } @article {pmid11499843, year = {2001}, author = {Farshid, G and Moinfar, F and Meredith, DJ and Peiterse, S and Tavassoli, FA}, title = {Spindle cell ductal carcinoma in situ. An unusual variant of ductal intra-epithelial neoplasia that simulates ductal hyperplasia or a myoepithelial proliferation.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {439}, number = {1}, pages = {70-77}, doi = {10.1007/s004280100446}, pmid = {11499843}, issn = {0945-6317}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/diagnostic imaging/*pathology/surgery ; Carcinoma in Situ/chemistry/diagnostic imaging/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/chemistry/diagnostic imaging/*pathology/surgery ; Cell Division ; Diagnosis, Differential ; Endothelium/pathology ; Female ; Follow-Up Studies ; Humans ; Hyperplasia/pathology ; Immunohistochemistry ; Keratins/analysis ; Mammography ; Middle Aged ; Treatment Outcome ; }, abstract = {Seventeen examples of a variant of ductal carcinoma in situ (DCIS) composed exclusively or predominantly of spindle cells arranged in fascicles, whorls, and solid sheets are described. The fascicular arrangement of the spindle cells simulates the "streaming" phenomenon associated with ordinary intraductal epithelial hyperplasia (IDH). This process also resembles the myoid, solid form of intraductal myoepithelial proliferation. The women ranged in age from 38 years to 79 years with a mean age of 59.3 years. Five patients presented with a palpable mass. The remaining tumors were discovered using mammography. The radiological appearances of the lesions raised concern for carcinoma, but there were no distinctive mammographic findings to suggest an unusual variant of DCIS. Cytological preparations were suspicious for malignancy in two patients and were reported as malignant in another case. Sixteen patients were treated with wide local excision, and one woman had a partial mastectomy. The tumors measured from 3 mm to 15 mm (mean 8.65 mm). In three cases, minute foci of stromal invasion were associated with the spindle cell DCIS. In another specimen, a 2.7-cm invasive ductal carcinoma of no special type was identified in an area away from the foci of the spindle cell DCIS. None of the patients has experienced recurrence or metastasis during the relatively short mean follow-up period of 16.2 months (range 4-77 months). Spindle cell DCIS is distinguished from the streaming pattern of ordinary IDH by its solid growth pattern, lack of secondary spaces or peripheral fenestrations, uniformity of appearance and distribution of nuclei, cytological atypia in the range of low to intermediate-grade DCIS, and negative immunoreaction with CK-34betaE12 (HMW-CK903). When fenestrations are present, they are evident in areas of cribriform DCIS that merge with the solid, spindle cell areas in hybrid ducts harboring both patterns. This admixture, with conventional cribriform DCIS, and the association with foci of invasive ductal carcinoma in some cases further help recognition and confirmation of this lesion as in situ carcinoma. When there is no transition from the spindle cells to recognizable cribriform DCIS, distinction from intraductal myoepithelial hyperplasia (myoepitheliosis) requires immunostains for actin and S-100 protein. Recognition of this pattern of DCIS is important in order to avoid its frequent misclassification as a benign lesion.}, } @article {pmid11496315, year = {2001}, author = {Kurosumi, M and Suemasu, K and Tabei, T and Inoue, K and Matsumoto, H and Sugamata, N and Higashi, Y}, title = {Relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis in invasive ductal carcinoma of the breast.}, journal = {Oncology reports}, volume = {8}, number = {5}, pages = {1051-1055}, doi = {10.3892/or.8.5.1051}, pmid = {11496315}, issn = {1021-335X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Female ; Humans ; Immunoenzyme Techniques ; Keratins/metabolism ; Lymph Node Excision ; Lymph Nodes/metabolism/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Postmenopause ; Premenopause ; Prognosis ; }, abstract = {Specimens obtained from 92 patients with invasive ductal carcinoma of the breast by quadrantectomy and axillary lymph node dissection were examined to evaluate the relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis. The number of lymphatic invasions was classified into 4 groups (ly0-3) by counting the number of peritumoral lymphatic invasions. In addition, immunohistochemistry for cytokeratin was performed to locate micrometastasis in the dissected lymph nodes. Thirty-seven (40.2%) of 92 cases had foci of lymphatic invasion and 29 (31.5%) cases revealed lymph node metastasis on initial routine examination. The rate of diagnosis of lymph node metastasis assessed by the existence of lymphatic invasion had an accuracy of 84.8%, a sensitivity of 89.7% and a specificity of 82.5%. On the other hand, all 3 cases (4.8%) with micrometastasis detected by immunohistochemistry for cytokeratin, showed lymphatic invasion. The rate of diagnosis after detection of micrometastasis increased and exhibited 88.0% accuracy. In addition, the rate of prediction of lymph node metastasis in cases with tumor larger than 15 mm was also high, and its accuracy was 88.2%. These results suggest that the assessment of peritumoral lymphatic invasion is very useful for predicting the presence of axillary lymph node metastasis including micrometastasis. They also suggest that excision specimens should be examined for lymphatic invasion, and that the results of the examination might be necessary to pick up false-negative cases and those at high risk for lymph node metastasis among patients who have not undergone lymph node dissection based on the result of sentinel lymph node biopsy.}, } @article {pmid11486901, year = {2001}, author = {Artuch, R and Colomé, C and Vilaseca, MA and Sierra, C and Cambra, FJ and Lambruschini, N and Campistol, J}, title = {Plasma phenylalanine is associated with decreased serum ubiquinone-10 concentrations in phenylketonuria.}, journal = {Journal of inherited metabolic disease}, volume = {24}, number = {3}, pages = {359-366}, pmid = {11486901}, issn = {0141-8955}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Cholesterol/blood ; Cholesterol, Dietary/administration & dosage ; Humans ; Infant ; Linear Models ; Phenylalanine/*blood ; Phenylketonurias/*blood/diet therapy ; Tyrosine/blood ; Ubiquinone/*blood ; }, abstract = {Decreased serum ubiquinone-10 concentrations is a common condition in patients with phenylketonuria (PKU) under dietary treatment. Our aim was to investigate the implication of the metabolic abnormalities of PKU (low concentrations of tyrosine and high concentrations of phenylalanine) and the effect of treatment with phenylalanine-restricted diets in decreased ubiquinone-10 concentrations in PKU patients. We studied 30 PKU patients (age range 5 months to 35 years; median age 7 years) under dietary treatment. Correlation between plasma tyrosine or phenylalanine and serum ubiquinone-10 concentrations was investigated. Daily cholesterol intake was calculated from the data obtained through a dietary questionnaire. The index of dietary control (IDC) was calculated as the average of the medians of plasma phenylalanine concentrations obtained every 6 months in the metabolic control of patients. Negative correlations were observed between serum ubiquinone and the IDC (r=-0.46; p<0.01) in PKU patients. No correlation was observed between tyrosine or daily cholesterol intake and serum ubiquinone concentrations. After adjustment for daily cholesterol intake by multiple linear regression analysis, for each 113 units of increase in IDC values serum ubiquinone decreased 0.1 micromol/L. According to our results, the main factor associated with the decreased serum ubiquinone concentrations was high plasma phenylalanine values. Although daily cholesterol intake seems to be associated with ubiquinone concentrations, it may not be relevant if we take into account the low intake of cholesterol in treated PKU patients.}, } @article {pmid11484500, year = {2001}, author = {Maluf, H and Koerner, F}, title = {Lobular carcinoma in situ and infiltrating ductal carcinoma: frequent presence of DCIS as a precursor lesion.}, journal = {International journal of surgical pathology}, volume = {9}, number = {2}, pages = {127-131}, doi = {10.1177/106689690100900206}, pmid = {11484500}, issn = {1066-8969}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Cadherins ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Middle Aged ; }, abstract = {Infiltrating ductal carcinoma (IDC) occurs frequently in patients with lobular carcinoma in-situ (LCIS). LCIS is not thought to be the direct precursor of the invasive component. The authors analyzed 15 cases of coexisting LCIS and IDC and found ductal carcinoma in situ (DCIS) in 12. The DCIS and IDC were of similar grade and located in the same area. Selected cases stained with E-cadherin demonstrated a different immunophenotype for the lobular and ductal lesions. These results support the notion that DCIS is the direct precursor of IDC occurring in patients with LCIS.}, } @article {pmid11482192, year = {2001}, author = {Sorkin, VM and Efetov, VM and Shcherbakov, GV}, title = {[Histological structure of a tumor as a criterion of primary multiplicity in bilateral cancer of mammary glands].}, journal = {Klinichna khirurhiia}, volume = {}, number = {4}, pages = {40-42}, pmid = {11482192}, issn = {0023-2130}, mesh = {Breast Neoplasms/*pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Neoplasms, Multiple Primary/*pathology ; }, abstract = {Comparative estimation of histological structure of contralateral tumors in 104 patients with primary and in 54--with metastatic mammarial gland cancer (MGC) was performed. Revealing of various histological types of tumoral nodes--of a one component infiltrating ductal cancer (IDC) in one mammarial gland and a one-component infiltrating lobular cancer (IPC)--in another one, combination of special form of the MGC with IDC and/or IPC, combination of cancer in situ with invasive form of the MGC constitutes the criterion of primarily-multiple affection. In differentiated diagnosis of primary and metastatic tumor this criterion is highly specific (92.9%), but has low prognostic value (37.5%). That's why in 73% of women-patients it is necessary to analyze the clinical examination data in addition to establish the diagnosis of primary bilateral MGC.}, } @article {pmid11479429, year = {2001}, author = {Lana, AM and Wen, DR and Cochran, AJ}, title = {The morphology, immunophenotype and distribution of paracortical dendritic leucocytes in lymph nodes regional to cutaneous melanoma.}, journal = {Melanoma research}, volume = {11}, number = {4}, pages = {401-410}, doi = {10.1097/00008390-200108000-00011}, pmid = {11479429}, issn = {0960-8931}, support = {CA29605/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antigen Presentation ; Cell Size ; Dendritic Cells/*immunology/pathology ; Female ; HLA-DR Antigens/immunology ; Humans ; Immunohistochemistry ; *Immunophenotyping ; Leukocytes/immunology/pathology ; Lymph Nodes/*immunology/pathology ; Male ; Melanoma/*immunology/pathology ; Middle Aged ; Neoplasm Metastasis/immunology ; Neoplasm Staging ; Skin Neoplasms/*immunology/pathology ; }, abstract = {Our aim was to identify and delineate alterations in the distribution and immunophenotype of the lymphocytes and paracortical dendritic leucocytes (interdigitating dendritic cells; IDCs) in lymph nodes regional to tumours. Using immunocytochemistry and computer-assisted image analysis we examined 65 lymph nodes excised from 47 patients with malignant melanoma. Twenty-nine patients had American Joint Committee on Cancer (AJCC) stage II melanoma (no tumour spread beyond the primary site) and 18 had AJCC stage III disease (metastases in the regional nodes). There were significant differences in the frequency, morphology, immunophenotype and anatomical distribution of the IDCs and in the complexity of their dendritic processes in different areas within individual lymph nodes. We conclude that morphological and phenotypical variations in IDCs correlate with differing levels of antigen presentation. Downregulation of antigen presentation in lymph nodes regional to tumours is most probably mediated by tumour products. Differences in IDC distribution and characteristics in lymph nodes from different anatomical sites must be considered in interpreting studies of nodal morphology and function.}, } @article {pmid11473487, year = {2001}, author = {Grassi, G and Seravalle, G and Bertinieri, G and Turri, C and Stella, ML and Scopelliti, F and Mancia, G}, title = {Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy.}, journal = {Clinical science (London, England : 1979)}, volume = {101}, number = {2}, pages = {141-146}, pmid = {11473487}, issn = {0143-5221}, mesh = {Adult ; Aged ; Analysis of Variance ; Baroreflex/drug effects/*physiology ; Blood Pressure/drug effects/physiology ; Cardiomyopathy, Dilated/blood/*complications/physiopathology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; Female ; Heart Failure/blood/etiology/*physiopathology ; Heart Rate/drug effects/physiology ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/blood/*complications/physiopathology ; Nitroprusside/pharmacology ; Norepinephrine/blood ; Phenylephrine/pharmacology ; Renin/blood ; Stroke Volume/drug effects/physiology ; Sympathetic Nervous System/drug effects/*physiopathology ; Vasodilator Agents/pharmacology ; }, abstract = {Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.}, } @article {pmid11470070, year = {2001}, author = {Ruibal, A and Arias, JI and Resino, C and Lapeña, G and Schneider, J and Tejerina, A}, title = {[Study of the cytosolic concentrations of the tissue poly-peptide specific (TPS) antigen in infiltrating ductal carcinomas of the breast. Positive relationship with hormone dependency and negative with cellular proliferation].}, journal = {Revista espanola de medicina nuclear}, volume = {20}, number = {5}, pages = {365-368}, doi = {10.1016/s0212-6982(01)71975-1}, pmid = {11470070}, issn = {0212-6982}, mesh = {Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Cathepsin D/analysis ; Cell Cycle ; Cell Division ; Cytosol/*chemistry ; *Estrogens ; Female ; Humans ; Immunoradiometric Assay ; Lymphatic Metastasis ; Neoplasm Metastasis ; Neoplasm Proteins/*analysis ; Neoplasms, Hormone-Dependent/*chemistry/pathology ; Ploidies ; *Progesterone ; Proteins/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tissue Plasminogen Activator/analysis ; Tissue Polypeptide Antigen/*analysis ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; }, abstract = {INTRODUCTION: The tissue-specific polypeptide antigen (TPS) is an epitope of the tissue polypeptide antigen (TPA) which is defined by the M3 monoclonal antibody and is related to cytokeratin 18. Several groups have demonstrated its value as a useful parameter in the follow-up of some tumors. This work has aimed to study the TPS cytosolic levels in infiltrating ductal carcinomas of the breast (IDC) and their possible correlations with other clinical-biological parameters.

PATIENTS AND METHODS: The TPS was determined by means of an immunoradiometric assay (Beki Diagnostics. Sweden). Other parameters included in the study were the estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D, tissue-type plasminogen activator (t-PA), tumor size, axillary lymph node involvement, distant metastases, histological grade, ploidy and S-phase.

RESULTS: The TPS cytosolic levels ranged from 1.8 to 606.3 KU/mg prt. (median 110.2) and had a significant correlation with the ER (r: 0.721), PR (r: 0.287), cathepsin D (r: 0.550) and t-PA (r:0.436). The TPS positive (> 110.2 KU/mg prt.) carcinomas had higher levels of ER (p: 0.001), PR (p: 0.021), pS2 (p: 0.058), cathepsin D (p: 0.000) and t-PA (p: 0.053) than the TPS negative tumors. When the IDC were classified according to S-phase values, we observed that the positive cases (S-phase > 8.1%, which represents the median value of all carcinomas) had lower levels of TPS (p: 0.046) than the negative tumors. Likewise, the GoG1 cellular fraction correlated positively and significantly with the TPS cytosolic levels (p: 0.000).

CONCLUSIONS: Based on our results, we suggest that there is a positive correlation between the TPS cytosolic levels and hormone-dependence parameters, as well as an inverse correlation between these and the cellular proliferation parameters. Based on the above, we consider that it is worthwhile to carry out further studies on cytosolic TPS in order to investigate its possible value as a prognostic parameter in breast carcinomas.}, } @article {pmid11458280, year = {2001}, author = {Székely, E and Madaras, L and Kulka, J and Járay, B and Nagy, L}, title = {Leiomyosarcoma of the female breast.}, journal = {Pathology oncology research : POR}, volume = {7}, number = {2}, pages = {151-153}, pmid = {11458280}, issn = {1219-4956}, mesh = {Actins/analysis ; Aged ; Biomarkers, Tumor/analysis ; Biopsy, Needle ; Breast Neoplasms/chemistry/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis ; Desmin/analysis ; Diagnosis, Differential ; Female ; Humans ; Leiomyosarcoma/chemistry/diagnosis/*pathology ; Neoplasm Proteins/analysis ; Phyllodes Tumor/diagnosis ; Vimentin/analysis ; }, abstract = {Leiomyosarcomas of the breast are rare tumors. Less than 15 such cases have been reported in the literature so far. In this paper authors describe a case of leiomyosarcoma of a female breast presenting as a firm lobulated mass, mimicking a phylloid tumor radiographically. By fine needle aspiration biopsy, on the smears discohesive malignant looking cells were conclusive to a poorly differentiated invasive ductal carcinoma of the breast. The mastectomy specimen contained a lobulated mass, microscopically showing a partly epithelioid spindle cell tumor, immunoreactive for vimentin, desmin, smooth muscle actin antibodies, and negative for epithelial markers, hormone and growth factor receptors. Axillary lymph nodes were free of tumor. A primary leiomyosarcoma of the breast was diagnosed.}, } @article {pmid11454996, year = {2001}, author = {Gamallo, C and Moreno-Bueno, G and Sarrió, D and Calero, F and Hardisson, D and Palacios, J}, title = {The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {7}, pages = {650-654}, doi = {10.1038/modpathol.3880367}, pmid = {11454996}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/*pathology ; Cadherins/*analysis ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cohort Studies ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Survival Analysis ; }, abstract = {We have immunohistochemically investigated P-cadherin (P-CD) expression in a series of 210 infiltrating ductal carcinomas (IDC) in an attempt to assess the biological and prognostic relevance of P-CD in patients harboring IDCs. Although only 74/210 (35%) of IDCs expressed P-CD in >5% of tumor cells (P-CD-positive carcinomas), categorical analyses revealed that P-CD-positive IDCs were larger (26 +/- 21 cm versus 22 +/- 11 cm, P =.0568), of higher histological grade (P =.0001), and had more lymph node metastases (P =.0327) than P-CD-negative breast carcinomas. In addition, P-CD-positive tumors were negative for estrogen (P =.0001) and progesterone receptors (P =.0001) and showed reduced E-cadherin expression (P =.0276) more frequently than P-CD-negative tumors. Univariate analysis carried out in 171 patients demonstrated that P-CD expression was also an indicator of poor prognosis (chi(2) = 8.292, P =.004), extent of lymph node metastasis (chi(2) = 20.854, P =.0000), histological grade (chi(2) = 12.908, P =.0016), and negative progesterone receptors (chi(2) = 4.116, P =.042). However, only histological grade and nodal metastases emerged as independent prognostic markers in the multivariate analysis. These results suggest that although P-CD expression may be involved in the progression of IDCs, its value as an independent prognostic factor remains to be established.}, } @article {pmid11451270, year = {2001}, author = {Schimke, I and Müller, J and Priem, F and Kruse, I and Schön, B and Stein, J and Kunze, R and Wallukat, G and Hetzer, R}, title = {Decreased oxidative stress in patients with idiopathic dilated cardiomyopathy one year after immunoglobulin adsorption.}, journal = {Journal of the American College of Cardiology}, volume = {38}, number = {1}, pages = {178-183}, doi = {10.1016/s0735-1097(01)01309-2}, pmid = {11451270}, issn = {0735-1097}, mesh = {Adsorption ; Adult ; Autoantibodies/blood ; Cardiomyopathy, Dilated/*physiopathology/therapy ; Female ; Humans ; Immunoglobulins/*blood ; Immunosorbent Techniques ; Lipid Peroxides/blood ; Male ; Middle Aged ; *Oxidative Stress ; Thiobarbituric Acid Reactive Substances ; }, abstract = {OBJECTIVES: In a substudy to a recently reported investigation that demonstrated the benefit of immunoglobulin adsorption (immunoadsorption) for patients with idiopathic dilated cardiomyopathy (IDC), we tested whether this benefit is associated with a reduction of oxidative stress.

BACKGROUND: The progression of cardiomyopathy is believed to be related to the increase of oxidative stress. Therefore, reduction of oxidative stress could be one of the effects of immunoadsorption for improvement of cardiac performance and clinical status.

METHODS: Plasma markers for oxidative stress-thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO), anti-oxidized low-density lipoprotein-autoantibodies (anti-oxLDL-AB), thiol groups and vitamin E-were compared in 31 patients, of whom 16 underwent immunoadsorption and 15 received conventional treatment (controls). All patients received a daily supplement of vitamins, minerals and trace elements.

RESULTS: After one year, TBARS (p = 0.026), LPO (p = 0.026) and anti-oxLD}, } @article {pmid11446840, year = {2001}, author = {Patel, MI and Watts, W and Grant, A}, title = {The optimal form of urinary drainage after acute retention of urine.}, journal = {BJU international}, volume = {88}, number = {1}, pages = {26-29}, doi = {10.1046/j.1464-410x.2001.02253.x}, pmid = {11446840}, issn = {1464-4096}, mesh = {Acute Disease ; Aged ; Aged, 80 and over ; Catheters, Indwelling ; Drainage/*methods ; Feasibility Studies ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Prospective Studies ; Self Care/methods ; Treatment Outcome ; Urinary Catheterization/*methods ; Urinary Retention/complications/*therapy ; Urinary Tract Infections/complications ; }, abstract = {OBJECTIVE: To assess the outcome of different forms of urinary drainage, particularly for urinary tract infection (UTI), operative findings and patient preference, in patients treated for acute urinary retention (AUR).

PATIENTS AND METHODS: A feasibility trial was conducted of men presenting with AUR; after a short period of indwelling catheterization (IDC) patients were taught how to use clean intermittent self-catheterization (CISC). Patients who failed this were re-catheterized and taught to manage a valve, or failing this a leg bag, and then discharged home. The patients were followed to assess the occurrence of spontaneous voiding, UTI, findings at prostatectomy and patient satisfaction.

RESULTS: The CISC group (34 men) had a higher rate of spontaneous voiding than the IDC group (16 men; 56% vs 25%). The incidence of UTI was 32% in the CISC and 75% in the IDC group. At TURP, 20% in the CISC group had a UTI, compared with 69% in the IDC group. Patients using CISC preferred it and had fewer complications than the IDC group. The CISC group had a similar ability to manage and similar acceptance of their method of drainage as the IDC group.

CONCLUSION: CISC is managed and accepted well by patients who can use the technique and results in fewer UTIs. It should be considered in patients who present with AUR, and it may delay surgery.}, } @article {pmid11439345, year = {2001}, author = {Cheng, CW and Wu, PE and Yu, JC and Huang, CS and Yue, CT and Wu, CW and Shen, CY}, title = {Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene.}, journal = {Oncogene}, volume = {20}, number = {29}, pages = {3814-3823}, doi = {10.1038/sj.onc.1204505}, pmid = {11439345}, issn = {0950-9232}, mesh = {Adaptor Proteins, Signal Transducing ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; MutL Protein Homolog 1 ; Neoplasm Proteins/genetics ; Nuclear Proteins ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Snail Family Transcription Factors ; Transcription Factors/genetics ; WT1 Proteins ; }, abstract = {Loss of heterozygosity (LOH) allows the expression of recessive mutation in tumor suppressor genes (TSG). Therefore, on the basis of Knudson's 'two-hit' hypothesis for TSG inactivation, the detection of a high LOH frequency in a chromosomal region is considered critical for TSG localization. One of these LOH regions in breast cancer is 16q22.1, which has been suggested to reflect the involvement of E-cadherin (E-cad), a cell-cell adhesion molecule. To confirm the tumorigenic role of E-cad, 81 sporadic invasive ductal carcinomas (IDCs) of the breast were tested for the 'two hits' required to inactivate this gene. A high frequency (37.3%) of LOH was detected in 67 informative tumors, but no mutation was found. To examine the possibility that transcriptional mechanisms serve as the second hit in tumors with LOH, specific pathways, including genetic variant and hypermethylation at the promoter region and abnormal expression of positive (WT1) and negative (Snail) transcription factors, were identified. Of these, promoter hypermethylation and increased expression of Snail were found to be common (>35%), and to be strongly associated with reduced/negative E-cad expression (P<0.05). However, unexpectedly, a significantly negative association was found between the existence of LOH and promoter hypermethylation (P<0.05), which contradicts the 'two-hit' model. Instead, since they coexisted in a high frequency of tumors, hypermethylation may work in concert with increased Snail to inactivate E-cad expression. Given that E-cad is involved in diverse mechanisms, loss of which is beneficial for tumors to invade but may also trigger apoptosis, this study suggests that maintaining a reversible mechanism, either by controlling the gene at the transcriptional level or by retaining an intact allele subsequent to LOH, might be important for E-cad in IDC and may also be common in TSGs possessing diverse functions. These findings provide clues to explain why certain TSGs identified by LOH cannot fulfil the two-hit hypothesis.}, } @article {pmid11438461, year = {2001}, author = {Takahashi, K and Kenji, A and Norihiro, T and Eisaku, K and Takashi, O and Kazuhiko, H and Tadashi, Y and Tadaatsu, A}, title = {Morphological interactions of interdigitating dendritic cells with B and T cells in human mesenteric lymph nodes.}, journal = {The American journal of pathology}, volume = {159}, number = {1}, pages = {131-138}, pmid = {11438461}, issn = {0002-9440}, mesh = {Aged ; B-Lymphocytes/*physiology ; Cell Aggregation ; *Cell Communication ; Cells, Cultured ; Dendritic Cells/*physiology ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Lymph Nodes/*cytology ; Mesentery ; Middle Aged ; T-Lymphocytes/*physiology ; Time Factors ; }, abstract = {Interdigitating dendritic cells (IDC) of the human mesenteric lymph nodes (LN) were examined by two-color immunofluorescent microscopy and flow cytometry to clarify their exact localization, immunophenotype, and relationships with T and B cells. IDC were identified as HLA-DR(bright) large dendriform cells of the T cell areas co-expressing CD40, CD54 (ICAM-1), CD80 (B7/B7-1), CD83, and CD86 (B70/B7-2). The majority of IDC directly attached to a few IgD+ naive B cells as well as to numerous CD4+ T cells. When LN cells were singly suspended and briefly incubated in vitro, IDC formed clusters with IgD+ IgM+ naive B cells, but not with IgA+ or IgG+ B cells. When suspended LN cells were cultured, clustered B cells disappeared within 7 days, and on prolonged culture, some IDC developed into extensively dendriform cells forming stable complexes with several or sometimes numerous CD4+ IL-2R+ CD40L+ activated T cells. These findings indicate that resting naive B cells actually interact with IDC directly in T cell areas of human secondary lymphoid tissues. IDC have a non-antigen (Ag)-specific, strong affinity for resting naive B cells, but this affinity is transient and IDC cannot form stable complexes with B cells, although they can form stable complexes with activated T cells. It is suggested that the stable IDC/Ag-activated T cell complexes make it possible to capture and to stimulate rare Ag-specific resting naive B cells with high efficiency.}, } @article {pmid11431676, year = {2001}, author = {La Vecchia, L and Zanolla, L and Varotto, L and Bonanno, C and Spadaro, GL and Ometto, R and Fontanelli, A}, title = {Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction.}, journal = {American heart journal}, volume = {142}, number = {1}, pages = {181-189}, doi = {10.1067/mhj.2001.116071}, pmid = {11431676}, issn = {0002-8703}, mesh = {Adult ; Cardiomyopathy, Dilated/*etiology/physiopathology ; Chi-Square Distribution ; Coronary Angiography ; Female ; Hemodynamics ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Ischemia/complications/physiopathology ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Stroke Volume ; Systole ; Ventricular Dysfunction, Left/*complications/physiopathology ; Ventricular Dysfunction, Right/*complications/physiopathology ; }, abstract = {BACKGROUND: Evidence for the role of right ventricular (RV) function is emerging in patients with heart failure of different etiologies. Studies conducted in dilated cardiomyopathy (IDC) showed a high prevalence of RV dysfunction unrelated to the severity of pulmonary hypertension. The aim of the study was to investigate the role of RV dysfunction in ischemic versus nonischemic patients.

METHODS: A series of 153 patients with left ventricular (LV) dysfunction (defined as a LV ejection fraction <45%) of either ischemic (n = 61, coronary artery disease [CAD] group) or nonischemic (n = 92, IDC group) origin were studied invasively. Besides routine catheterization data, RV volumes and ejection fractions were obtained angiographically. Reference data were collected in a control group of healthy subjects. RV dysfunction was defined as a RV ejection fraction <35% and ventricular concordance as a <10% difference between RV and LV ejection fraction. The LV/RV end-diastolic volume ratio was calculated to assess the relative dilatation of the ventricular chambers. Hemodynamic and angiographic data were compared in the 2 groups by univariate and multivariate logistic regression analysis.

RESULTS: Patients with IDC and CAD had comparable LV ejection fractions (29% +/- 3% vs 31% +/- 8%, P not significant) and mean pulmonary pressures (27 +/- 12 mm Hg vs 26 +/- 11 mm Hg, P not significant); the LV/RV end-diastolic volume ratio was identical in the 2 groups (1.26 +/- 0.4 vs 1.24 +/- 0.4, P not significant). RV ejection fraction was significantly lower in IDC compared with CAD (33% +/- 10 % vs 46% +/- 11%, P <.0001), with a prevalence of RV dysfunction in the IDC group of 65% compared with 16% in the CAD group (P <.0001); similarly, the prevalence of ejection fraction concordance was 74% versus 33%, respectively (P <.0001). At multivariate analysis, a low RV ejection fraction was a powerful independent predictor of IDC compared with CAD (odds ratio 0.91, 95% confidence interval 0.87-0.94, P <.0001). RV dysfunction had a positive predictive value of 75% and a negative predictive value of 78% for the diagnosis of IDC; for ventricular concordance, these values were 81% and 69%, respectively. The correlation between mean pulmonary artery pressure and RV ejection fraction was weaker in the IDC group compared with the CAD group (R(2) = 0.032, P =.047 and R(2) = 0.172,P <.0001, respectively).

CONCLUSION: In the presence of LV dysfunction, a reduced RV ejection fraction is a powerful marker for IDC compared with CAD, independent of age, pulmonary hypertension, LV function, and ventricular dimensions. These findings support the concept that IDC is frequently characterized by a biventricular involvement and that the presence of RV dysfunction represents a distinguishing feature of this disease.}, } @article {pmid11422790, year = {2001}, author = {Moriya, T and Suzuki, T and Pilichowska, M and Ariga, N and Kimura, N and Ouchi, N and Nagura, H and Sasano, H}, title = {Immunohistochemical expression of gonadotropin releasing hormone receptor in human breast carcinoma.}, journal = {Pathology international}, volume = {51}, number = {5}, pages = {333-337}, doi = {10.1046/j.1440-1827.2001.01210.x}, pmid = {11422790}, issn = {1320-5463}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*metabolism/pathology ; Carcinoma, Ductal, Breast/chemistry/*metabolism/secondary ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/chemistry ; Lymph Nodes/pathology ; Menopause ; Middle Aged ; Neoplasm Staging ; Receptors, Estrogen/analysis/metabolism ; Receptors, LHRH/analysis/*metabolism ; Receptors, Progesterone/analysis/metabolism ; }, abstract = {Gonadotropin releasing hormone (GnRH) analogs can cause regression of hormone-dependent breast carcinomas via the specific GnRH receptor (GnRH-R). In an attempt to obtain a better understanding of GnRH actions in human breast carcinoma, the expression of GnRH-R was examined immunohistochemically in 58 invasive ductal carcinomas and correlated with various clinicopathological parameters. GnRH-R was immunolocalized in the cytoplasm of carcinoma cells in 37 of 58 invasive ductal carcinoma cases (64%). Immunoreactivity for GnRH-R was also detected focally in the cytoplasm of morphologically normal glandular epithelia adjacent to the carcinoma. A significant correlation was observed between the immunohistochemical expression of GnRH-R and estrogen receptor labeling index (LI; P = 0.030) or progesterone receptor LI (P = 0.0074). There was a significant inverse correlation between GnRH-R immunoreactivity and Ki-67 LI (P = 0.012). No significant correlations were detected between GnRH-R and other clinicopathological parameters, including patient age, menopausal status, stage, tumor size, lymph node status, histological grade and prognosis. This study indicates that GnRH-R is widely distributed in human breast carcinoma cells and regulates GnRH actions locally. Breast carcinomas positive for GnRH-R maintain some hormonal regulatory mechanisms, and GnRH actions may lead to a low proliferative rate in human breast carcinoma.}, } @article {pmid11409797, year = {2001}, author = {Cox, CE and Nguyen, K and Gray, RJ and Salud, C and Ku, NN and Dupont, E and Hutson, L and Peltz, E and Whitehead, G and Reintgen, D and Cantor, A}, title = {Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS?.}, journal = {The American surgeon}, volume = {67}, number = {6}, pages = {513-9; discussion 519-21}, pmid = {11409797}, issn = {0003-1348}, support = {R21 CA66553-01/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology/surgery ; Female ; Humans ; Lymph Node Excision/economics ; Lymphatic Metastasis ; Mastectomy/economics ; Mastectomy, Segmental/economics ; Neoplasm Invasiveness/pathology ; Prospective Studies ; Risk Factors ; *Sentinel Lymph Node Biopsy/economics ; Staining and Labeling ; }, abstract = {The appropriateness of sentinel lymph node biopsy in the management of patients with biopsy diagnoses of ductal carcinoma in situ (DCIS) or DCIS with microinvasion (DCISM) has not been established. Three hundred forty-one patients presented with a biopsy diagnosis of DCIS or DCISM. Two hundred forty (70%) underwent sentinel node biopsy at their definitive procedure. All clinical and pathologic data were collected prospectively. Of 224 patients with a biopsy diagnosis of DCIS 23 (10%) were upstaged to infiltrating ductal carcinoma (IDC) at their definitive therapy and of 16 patients with a biopsy diagnosis of DCISM seven (44%) were upstaged to IDC. Excisional biopsies were no more sensitive for detecting IDC than was core biopsy. Lymph node metastases were detected in 26 of 195 (13%) patients with a definitive diagnosis of DCIS, in three of 15 (20%) with a definitive diagnosis of DCISM, and in eight of 30 (27%) with a definitive diagnosis of IDC. Sentinel lymph node biopsy is a valuable tool in the treatment of patients with DCIS and DCISM and is particularly needed in those undergoing mastectomy. No "high-risk" group of patients can be identified for selective sentinel lymph node biopsy.}, } @article {pmid11400156, year = {2001}, author = {Sapino, A and Bongiovanni, M and Cassoni, P and Righi, L and Arisio, R and Deaglio, S and Malavasi, F}, title = {Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast.}, journal = {The Journal of pathology}, volume = {194}, number = {2}, pages = {254-261}, doi = {10.1002/1096-9896(200106)194:2<254::AID-PATH880>3.0.CO;2-2}, pmid = {11400156}, issn = {0022-3417}, mesh = {Aged ; Aged, 80 and over ; Anus Neoplasms/immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/blood supply/*immunology ; Carcinoma in Situ/blood supply/*immunology ; Carcinoma, Ductal, Breast/blood supply/*immunology ; Case-Control Studies ; Female ; Humans ; Hyaluronan Receptors/analysis ; Middle Aged ; *Neovascularization, Pathologic ; Paget Disease, Extramammary/immunology ; Paget's Disease, Mammary/immunology ; Platelet Endothelial Cell Adhesion Molecule-1/*analysis ; Vulvar Neoplasms/immunology ; }, abstract = {CD31, an adhesion molecule expressed by endothelial cells, leukocytes, and platelets, is used in surgical pathology as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis in breast carcinomas, CD31 expression was observed in a single case of large (5.2 cm diameter) high nuclear grade ductal carcinoma in situ (HG-DCIS) associated with poorly differentiated invasive ductal carcinoma (G3-IDC). Expression was limited to the cell membrane. This study focused on 32 HG-DCIS> or = 2 cm, either pure or associated with IDC. Cancer cells wereCD31(+) in 11 cases. Double staining using anti-CD31 monoclonal antibody (MAb) and anti-CD44 MAb, the anti-hyaluronate receptor, showed that foci of CD31(+) and CD44(-) tumour cells could be traced throughout the glandular tree, marking the intraductal diffusion of tumour up to Paget's cells at the nipple. The associated G3-IDC and their lymph node metastases were instead CD31(+) and CD44(+). CD31(+) tumours were oestrogen receptor (ER)(-), frequently p53(+) and c-erb-B2(+), and infiltrated by CD4(+) T lymphocytes. Normal and hyperplastic epithelia were constantly CD31(-). Other endothelial markers (e.g Factor VIII-RA and CD34) were not expressed by carcinoma cells, as was CD38, the CD31 ligand. In conclusion, CD31 expression is a feature acquired by breast cancer cells in the DCIS model. CD31 expression mainly correlates with tumour cells spreading within the ductal system. Finally, the invasive phenotype requires the co-expression of CD31 and CD44.}, } @article {pmid11391857, year = {2001}, author = {Minari, Y and Nio, Y and Hirahara, N and Dong, M}, title = {Heterogeneic distribution of thymidine phosphorylase between primary tumors and metastatic lesions of human pancreatic ductal carcinoma: implications for the efficacy of chemotherapy with 5-FU or its derivatives.}, journal = {Cancer chemotherapy and pharmacology}, volume = {47}, number = {5}, pages = {415-422}, doi = {10.1007/s002800000252}, pmid = {11391857}, issn = {0344-5704}, mesh = {Aged ; Antimetabolites, Antineoplastic/*pharmacokinetics/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy/*enzymology/mortality/secondary ; Chemotherapy, Adjuvant ; Female ; Fluorouracil/*pharmacokinetics/therapeutic use ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms/drug therapy/*enzymology/mortality/pathology ; Survival Rate ; Thymidine Phosphorylase/*metabolism ; Treatment Outcome ; }, abstract = {PURPOSE: It has been suggested that the expression of thymidine phosphorylase (TdRPase) correlates with the malignant potential of various cancers, but its involvement in human invasive ductal carcinoma (IDC) of the pancreas has not been reported. In the present study, the distribution and clinical significance of TdRPase in IDCs and benign diseases of the pancreas were assessed, especially in relation to the efficacy of chemotherapy with 5-FU or its derivatives.

METHOD: The expression of TdRPase in 148 specimens of pancreatic IDCs (66 primary lesions, 46 nodal lesions and 36 distant metastases from 126 patients) and in 24 specimens of benign diseases (4 cystadenomas, 3 hyperplasias, and 17 chronic pancreatitises) was examined by immunohistochemical staining with anti-TdRPase monoclonal antibody and evaluated in terms of three grades of immunoreactivity: negative 0, low 1, or high 2.

RESULTS: Positive TdRPase staining (low and high immunoreactivity) was detected in 71% (47/66) of the primary lesions, in 46% (21/46) of the involved nodes, in 53% (19/36) of various lesions of distant metastasis, and in 37% (9/24) of the benign diseases. The staining intensity was significantly higher in the IDC tissues than in the benign disease tissues, and significantly lower in the metastatic lesions than in the primary lesions. TdRPase reactivity did not correlate with the survival rate in both resectable and unresectable IDCs. In patients with both primary tumor and nodal involvement, however, high TdRPase activity in involved nodes was significantly associated with a poor prognosis. On the other hand, although adjuvant chemotherapy was found to improve the survival of patients, TdRPase activity in the tumor did not show any significant relationship with the efficacy of chemotherapy with 5-FU or its derivatives.

CONCLUSIONS: The present study suggested that in pancreatic IDC the activity of TdRPase in primary lesions is different from that in metastatic lesions, and that DNA is synthesized mainly through the salvage pathway in primary lesions and through a de novo pathway in metastatic lesions. This may be one of the reasons for the heterogeneity in chemosensitivity of human pancreatic IDC.}, } @article {pmid11391609, year = {2001}, author = {Park, K and Han, S and Kim, HY and Ko, I}, title = {Cytologic evaluation of cyclin D1 expression in primary breast carcinoma.}, journal = {Cancer}, volume = {93}, number = {3}, pages = {211-215}, doi = {10.1002/cncr.9031}, pmid = {11391609}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Biopsy, Needle ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cyclin D1/*metabolism ; Female ; Humans ; Immunoenzyme Techniques ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {BACKGROUND: Preoperative assessment of the biologic characteristics of primary breast carcinoma is important because neoadjuvant medical therapy is being used increasingly. In the current study, the authors attempted to evaluate the validity of cyclin D1 assay in fine-needle aspiration (FNA) samples from patients with primary breast carcinoma.

METHODS: FNA samples were obtained prior to therapy and multiple slides were stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA for cyclin D1 protein was performed on FNA samples from 51 breast carcinoma patients and 20 samples from patients with benign breast disease. In 45 breast carcinoma patients who had undergone surgery, sections were taken from paraffin blocks and stained by ICA for cyclin D1 validation. Possible correlations between cyclin D1 expression in the FNA samples and the biologic data of the patients also were analyzed.

RESULTS: Cyclin D1 expression was detected in 37 FNA samples from 51 breast carcinomas (72.5%) whereas expression of cyclin D1 was detected in 8 FNA samples from 20 patients with benign breast disease (40%). In histologic sections after surgery, 26 cases of breast carcinoma (65%) showed a positive reaction to cyclin D1. Concordance for the presence of cyclin D1 between FNA samples and histologic samples was 75%. Cyclin D1 expression was high in patients with the tumors that expressed estrogen receptor (ER) (30 of 34 vs. 5 of 11; P = 0.028) and progesterone receptor (PR) (33 of 38 vs. 2 of 7; P = 0.007). There was no significant relation found between cyclin D1 expression and tumor size or lymph node metastasis. Cyclin D1 expression within invasive ductal carcinoma was observed in > 80% of low or intermediate nuclear grade tumors but its expression decreased to 61.5% (8 of 13 cases) in tumors with high nuclear grade (P = 0.023). All 14 breast carcinomas in which the S-phase fraction was 15% showed cyclin D1 expression. Cyclin D1 expression was found to be correlated inversely with proliferative activity in breast carcinoma (P = 0.023).

CONCLUSIONS: The results of the current study show that cyclin D1 expression can be measured by ICA in FNA samples with reasonable concordance with the results of histologic section. Cyclin D1 expression was found to be associated with ER/PR status and cell differentiation. The results of the current study indicate that the measurement of novel molecular markers could be performed adequately in FNA samples as well as in histologic sections.}, } @article {pmid11386835, year = {2001}, author = {Irie, K and Kawanishi, M and Kunishio, K and Nagao, S}, title = {The efficacy and safety of transvenous embolisation in the treatment of intracranial dural arteriovenous fistulas.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {8 Suppl 1}, number = {}, pages = {92-96}, doi = {10.1054/jocn.2001.0886}, pmid = {11386835}, issn = {0967-5868}, mesh = {Aged ; Central Nervous System Vascular Malformations/diagnostic imaging/*therapy ; Cerebral Angiography ; Cerebral Arteries ; Embolization, Therapeutic/instrumentation/*methods ; Female ; Femoral Vein ; Humans ; Male ; Middle Aged ; Safety ; Treatment Outcome ; }, abstract = {To evaluate the role of transvenous embolisation including its efficacy and safety in the treatment of intracranial dural arteriovenous fistulas (DAVFs), we retrospectively analysed seven cases of intracranial DAVFs treated with transvenous embolisation in combination with arterial embolisation. Four DAVFs were in the cavernous sinus, two in the transverse-sigmoid sinus, and one in the inferior petrosal sinus. The transarterial and transvenous embolic agents included fibred platinum coils (FPC) and interlocking detachable coils (IDC). In all patients, the transarterial embolisation alone had failed to cure the DAVFs. After the combined transvenous embolisation, the anatomical cure was proven in five patients, and all patients were clinically cured. There were no complications in any patient. In conclusion, the transvenous embolisation is a useful and safe approach in the management of intracranial DAVFs.}, } @article {pmid11385691, year = {2001}, author = {Romanzi, LJ and Groutz, A and Heritz, DM and Blaivas, JG}, title = {Involuntary detrusor contractions: correlation of urodynamic data to clinical categories.}, journal = {Neurourology and urodynamics}, volume = {20}, number = {3}, pages = {249-257}, doi = {10.1002/nau.1002}, pmid = {11385691}, issn = {0733-2467}, mesh = {Female ; Humans ; Male ; Muscle Contraction ; Muscle Hypertonia/*classification/complications/*physiopathology ; Muscle, Smooth/physiopathology ; Urinary Bladder/*physiopathology ; Urinary Bladder Diseases/*classification/complications/*physiopathology ; Urinary Bladder, Neurogenic/etiology/physiopathology ; Urinary Incontinence/etiology/physiopathology ; Urinary Incontinence, Stress/etiology/physiopathology ; Urination Disorders/etiology/*physiopathology ; *Urodynamics ; }, abstract = {Data regarding the prevalence and urodynamic characteristics of involuntary detrusor contractions (IDC) in various clinical settings, as well as in neurologically intact vs. neurologically impaired patients, are scarce. The aim of our study was to evaluate whether the urodynamic characteristics of IDC differ in various clinical categories. One hundred eleven consecutive neurologically intact patients and 21 consecutive neurologically impaired patients, referred for evaluation of persistent irritative voiding symptoms, were prospectively enrolled. All patients were presumed by history to have IDC, and underwent detailed clinical and urodynamic evaluation. Based on clinical evaluation, patients were placed into one of four categories according to the main presenting symptoms and the existence of neurological insult: 1) frequency/urgency; 2) urge incontinence; 3) mixed stress incontinence and irritative symptoms; and 4) neurogenic bladder. IDC was defined by detrusor pressure of > or = 15 cm H2O whether or not the patient perceived the contraction; or < 15 cm H2O if perceived by the patient. Eight urodynamic characteristics of IDC were analyzed and compared between the four groups. IDC were observed in all of the neurologically impaired patients, compared with 76% of the neurologically intact patients (P < 0.001). No correlation was found between amplitude of IDC and subjective report of urgency. All clinical categories demonstrated IDC at approximately 80% of cystometric capacity. Eighty-one percent of the neurologically impaired patients, compared with 97% of the neurologically intact patients, were aware of the IDC at the time of urodynamics (P < 0.04). The ability to abort the IDC was significantly higher among continent patients with frequency/urgency (77%) compared with urge incontinent patients (46%) and neurologically impaired patients (38%). In conclusion, when evaluating detrusor overactivity, the characteristics of the IDC are not distinct enough to aid in differential diagnosis. However, the ability to abort IDC and stop incontinent flow may have prognostic implications, especially for the response to behavior modification, biofeedback, and pelvic floor exercise.}, } @article {pmid11377350, year = {2001}, author = {Ortiz, M and Almendral, J and López-Palop, R and Villacastín, J and Arenal, A}, title = {Determinants of inducibility of ventricular tachycardia.}, journal = {The American journal of cardiology}, volume = {87}, number = {11}, pages = {1255-1259}, doi = {10.1016/s0002-9149(01)01545-4}, pmid = {11377350}, issn = {0002-9149}, mesh = {Adult ; Aged ; *Cardiac Pacing, Artificial ; *Electrocardiography ; Female ; Heart Conduction System/physiopathology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Risk Factors ; Stroke Volume/physiology ; Tachycardia, Ventricular/*diagnosis/etiology/physiopathology ; }, abstract = {We analyzed the incidence and predictive factors for induction of clinical ventricular tachycardia (VT) during an electrophysiologic study in 127 patients with structural heart disease and spontaneous VT documented by 12-lead electrocardiography. Eighty-five patients had coronary artery disease (CAD), 24 had idiopathic dilated cardiomyopathy (IDC), and 18 had right ventricular dysplasia (RVD). Clinical variables were age, gender, electrocardiographic patterns of spontaneous arrhythmia, cardiac diagnosis, left ventricular (LV) ejection fraction (EF), infarct location, and presence of LV aneurysm. Clinical VT was induced in 76 patients (60%, group 1) and was not induced in 51 patients (group 2). Clinical VT was induced in 83% of patients with RVD, 58% of patients with CAD, and 50% of patients with IDC (p = 0.07). LVEF tended to be significantly higher in group 1 than in group 2 (p = 0.06). The presence of left QRS axis in the frontal plane during spontaneous VT was significantly associated with a higher inducibility both in the general group (69% vs 46%, p <0.02) and in patients with CAD (70% vs 44%, p <0.02). In patients with CAD, only the presence of a left QRS axis was significantly associated with a higher inducibility. A multivariate analysis identified only the left QRS axis as a significant and independent predictor of induction of clinical VT. The association of a leftward axis with inducibility suggests that vectorial factors in the depolarization wavefronts may be related to inducibility since conventional stimulation is performed from the right ventricle, producing a leftward axis in most cases.}, } @article {pmid11376305, year = {2001}, author = {Kawai, K and Hata, K and Takaoka, H and Kawai, H and Yokoyama, M}, title = {Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment.}, journal = {American heart journal}, volume = {141}, number = {6}, pages = {925-932}, doi = {10.1067/mhj.2001.115435}, pmid = {11376305}, issn = {0002-8703}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Carbazoles/*therapeutic use ; Cardiomyopathy, Dilated/blood/diagnostic imaging/*drug therapy ; Carvedilol ; Echocardiography ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Norepinephrine/blood ; Propanolamines/*therapeutic use ; ROC Curve ; *Ventricular Function, Left ; }, abstract = {BACKGROUND: Plasma brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. In the treatment of heart failure, especially in idiopathic dilated cardiomyopathy (IDC), beta-blocker (BB) therapy has been established as a powerful strategy. The purpose of this study was to analyze relationships between changes in BNP level and LV function during BB therapy in patients with IDC.

METHODS: In 30 patients with IDC who had already received conventional therapy, measurement for plasma BNP and norepinephrine levels and echocardiographic indices were evaluated before and 2 and 6 months after carvedilol in 21 patients and at baseline and after 6 months in 9 patients who did not receive carvedilol.

RESULTS: After 6 months carvedilol treatment significantly improved LV end-diastolic dimension (LVEDD) (65 +/- 8 to 61 +/- 8 mm) and LV ejection fraction (LVEF) (34% +/- 13% to 43% +/- 12%) with intergroup differences; it significantly decreased BNP (127 +/- 113 to 69 +/- 92 pg/mL) with no intergroup difference; however, it did not decrease norepinephrine. BNP correlated strongly with LVEDD, LVEF, and LV mass index in carvedilol-treated patients. The degree of change in BNP correlated with that in LVEDD or LVEF 6 months after carvedilol. All 14 patients with decreased or unchanged BNP levels showed an increase in LVEF, and 4 of 7 with a rise in BNP had decreased or unchanged LVEF. According to receiver operating characteristic analysis, the optimal BNP levels for detecting LVEF <35% before and after carvedilol were 75.5 and 69 pg/mL, respectively.

CONCLUSION: Plasma BNP levels may accurately reflect alteration in LV function and structure and can be used as a therapeutic indicator for risk stratification in patients with IDC during BB therapy.}, } @article {pmid11358433, year = {2001}, author = {Le, Y and Wetzel, MA and Shen, W and Gong, W and Rogers, TJ and Henderson, EE and Wang, JM}, title = {Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {99}, number = {3}, pages = {365-372}, doi = {10.1006/clim.2001.5021}, pmid = {11358433}, issn = {1521-6616}, support = {DA06650/DA/NIDA NIH HHS/United States ; DA11130/DA/NIDA NIH HHS/United States ; DA12113/DA/NIDA NIH HHS/United States ; F31DA05894/DA/NIDA NIH HHS/United States ; N01-CO-56000/CO/NCI NIH HHS/United States ; T32DA07237/DA/NIDA NIH HHS/United States ; }, mesh = {Cell Differentiation ; Chemokine CCL4 ; Chemokine CCL5/pharmacology ; Dendritic Cells/*physiology/virology ; Down-Regulation ; HIV-1/drug effects/physiology ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Phosphorylation ; Receptors, CCR5/*physiology ; Receptors, Formyl Peptide ; Receptors, Immunologic/*physiology ; *Receptors, Lipoxin ; Receptors, Peptide/*physiology ; }, abstract = {Chemokine receptors are subjected to heterologous desensitization by activation of formyl peptide receptors. We investigated the cross-talk between formyl peptide receptors and the chemokine receptor CCR5 in human monocyte-differentiated immature dendritic cells (iDC). Monocytes cultured with GM-CSF and IL-4 for 4 days exhibit markers characteristic of iDC and maintain the expression of both formyl peptide receptors FPR and FPRL1, as well as CCR5. Pretreatment of iDC with W peptide (WKYMVm), a potent agonist for FPR and FPRL1 but with preference for FPRL1, resulted in down-regulation of CCR5 from the cell surface and reduced cell response to the CCR5 ligands through a PKC-dependent pathway. Furthermore, W peptide induced a PKC-dependent phosphorylation of CCR5 and inhibited infection of iDC by R5 HIV-1. Our results indicate that the expression and functions of CCR5 in iDC can be attenuated by W peptide, which activates formyl peptide receptors, and suggest an approach to the design of novel anti-HIV-1 agents.}, } @article {pmid11357998, year = {2000}, author = {Andrade, SG and Pimentel, AR and de Souza, MM and Andrade, ZA}, title = {Interstitial dendritic cells of the heart harbor Trypanosoma cruzi antigens in experimentally infected dogs: importance for the pathogenesis of chagasic myocarditis.}, journal = {The American journal of tropical medicine and hygiene}, volume = {63}, number = {1-2}, pages = {64-70}, doi = {10.4269/ajtmh.2000.63.64}, pmid = {11357998}, issn = {0002-9637}, mesh = {Animals ; Antibodies, Monoclonal ; Antigens, Protozoan/isolation & purification ; Case-Control Studies ; Chagas Cardiomyopathy/immunology/*parasitology ; Dendritic Cells/*immunology/pathology ; Dogs ; Heart/parasitology ; Immunohistochemistry ; Myocarditis/immunology/*parasitology ; Myocardium/*cytology ; Trypanosoma cruzi/*pathogenicity ; }, abstract = {Heart sections from 16 mongrel dogs, two normal controls and 14 infected with Trypanosoma cruzi, were submitted to immunohistochemical staining with either rabbit anti-cow S100 Protein monoclonal antibody or rabbit anti-T. cruzi purified specific antibody, using the peroxidase technique to investigate the participation of the interstitial dendritic cells of the heart (IDCs) in myocarditis of Chagas disease. Trypanosoma cruzi antigens were revealed as granular and dense deposits in IDC membrane in the heart of infected dogs both during acute and chronic myocarditis, but not in normal controls. Anti-S100 Protein labeled the IDCs, both in normal and infected dogs and a significant increase in the numbers of IDCs occurred in the myocardium, proportionally to the intensity of the inflammatory infiltration. These findings suggest that IDCs, probably by presenting T. cruzi antigens to immune-competent cells, play an important role in the pathogenesis of Chagas disease.}, } @article {pmid11353046, year = {2001}, author = {Tsuda, H and Takarabe, T and Akashi-Tanaka, S and Fukutomi, T and Hirohashi, S}, title = {Pattern of chromosome 16q loss differs between an atypical proliferative lesion and an intraductal or invasive ductal carcinoma occurring subsequently in the same area of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {5}, pages = {382-388}, doi = {10.1038/modpathol.3880322}, pmid = {11353046}, issn = {0893-3952}, mesh = {Adult ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal, Breast/*genetics/pathology/surgery ; *Chromosomes, Human, Pair 16 ; DNA, Neoplasm/analysis ; Female ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; Middle Aged ; Papilloma, Intraductal/genetics/pathology ; Polymerase Chain Reaction ; Precancerous Conditions/*genetics/pathology/surgery ; }, abstract = {Atypical proliferative lesions of the breast, such as atypical ductal hyperplasia and atypical papilloma, are considered to be precursors of breast carcinomas and have frequently been shown to have loss of heterozygosity (LOH) on chromosome 16q at the DNA level. We evaluated whether an atypical proliferative lesion and a carcinoma that subsequently occurred in the same area of the ipsilateral breast were of identical clonal origin in seven patients. Using DNA isolated from microdissected archival tissue of epithelial components of both the biopsy specimen of the atypical proliferative lesion and the mastectomy specimen of the carcinoma, the pattern of LOH on 16q was compared between these two lesions using polymerase chain reaction -microsatellite LOH analysis. As a control, LOH on 16q was examined in 13 cases of usual ductal hyperplasia, 10 usual papillomas, and 6 atypical ductal hyperplasias. In the seven cases, LOH on 16q was detected in three of the six atypical proliferative lesions and in five of the seven carcinomas, but the allele with LOH or a deleted region always differed between the two. LOH was detected in both atypical proliferative lesions and carcinomas in one case, only in the atypical proliferative lesion in two cases, and only in carcinomas in three cases. In the controls, LOH on 16q was absent in usual ductal hyperplasias or usual papillomas but was detected in two of six atypical ductal hyperplasias. Although atypical proliferative lesions were frequently confirmed to be of clonal nature with LOH on 16q, these lesions and carcinomas were considered to be clones, probably originated from a field with these clones.}, } @article {pmid11348414, year = {2001}, author = {Diaz, LK and Wiley, EL and Morrow, M}, title = {Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast.}, journal = {The breast journal}, volume = {7}, number = {1}, pages = {40-45}, doi = {10.1046/j.1524-4741.2001.007001040.x}, pmid = {11348414}, issn = {1075-122X}, mesh = {Biomarkers, Tumor/*analysis ; Biopsy, Needle ; Breast/chemistry ; Breast Neoplasms/*chemistry/pathology ; Carcinoma in Situ/*chemistry ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Culture Techniques ; Female ; Humans ; Immunohistochemistry ; Mucin-1/*analysis/*genetics ; Mucin-2 ; Mucin-3 ; Mucins/*analysis ; Prognosis ; Sensitivity and Specificity ; }, abstract = {Epithelial mucins are glycoproteins secreted by epithelial cells and their carcinomas. At least nine mucin genes have been identified, and their products (MUC1-MUC9) are expressed in various epithelia. MUC1 is a mucin expressed in breast epithelial cells, whereas MUC2 and MUC3 are primarily intestinal mucins. Although MUC1 and MUC2 expression has been documented in invasive ductal carcinoma of the breast, mucin expression in pure ductal carcinoma in situ (DCIS) has not been investigated. Sixty-one of 105 cases of DCIS without coexisting infiltrating carcinoma diagnosed during a 30-month period were selected as having sufficient tissue for study. Paraffin-embedded tissue sections were stained using immunohistochemical techniques with mouse monoclonal anti-MUC1, anti-MUC2, and rabbit-specific polyclonal anti-MUC3 antibodies. Immunoreactive epitopes of MUC1, MUC2, and MUC3 were expressed in DCIS in 61, 19, and 16 of 61 cases, respectively. MUC2 and MUC3 staining intensity in DCIS was markedly less than that observed for MUC1. Luminal and/or cytoplasmic patterns of staining were observed for MUC1. MUC2 and MUC3 showed only cytoplasmic staining. Cytoplasmic-only staining of MUC1 was associated with a higher grade of DCIS. Any MUC2 staining was also associated with a higher grade of DCIS. Coexpression of MUC2 and MUC3 was present in only 6 of 61 cases, and MUC3 staining was unrelated to the grade of DCIS. Cytoplasmic expression of MUC1 and MUC2 appears to be associated with a higher grade of DCIS. MUC3 expression appears to be independent of grade and expression of MUC1 and MUC2. The relationship of mucin expression and grade warrants further study.}, } @article {pmid11348410, year = {2001}, author = {Méndez, I and Andreu, FJ and Sáez, E and Sentís, M and Jurado, I and Cabezuelo, MA and Castañer, E and Gallardo, X and Díaz-Ruiz, MJ and López, E and Marco, V}, title = {Ductal carcinoma in situ and atypical ductal hyperplasia of the breast diagnosed at stereotactic core biopsy.}, journal = {The breast journal}, volume = {7}, number = {1}, pages = {14-18}, doi = {10.1046/j.1524-4741.2001.007001014.x}, pmid = {11348410}, issn = {1075-122X}, mesh = {Biopsy, Needle/*methods ; Breast Neoplasms/*pathology/surgery ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology/surgery ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia/pathology ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {Stereotactic core needle biopsy (SCNB) allows specific histopathologic diagnoses to be made without surgery and has been demonstrated to be an accurate, cost-effective method of diagnosing breast disease, particularly nonpalpable lesions. However, recent studies have concluded that the diagnosis of atypical ductal hyperplasia (ADH) by means of SCNB has resulted in nearly equal odds that a coexisting malignant lesion will be missed. Furthermore, others have concluded that SCNB diagnosed as DCIS cannot reliably indicate the absence of tumor invasion in surgical excision. Between 1993 and 1998, 1,221 consecutive SCNB of mammographically identified lesions were performed using a 14-gauge automated device with an average of 5.3 cores obtained per lesion. ADH was identified in 19 (1.6%) lesions and DCIS in 89 (7.3%). Surgical biopsy was performed in 89 of these patients and histopathologic results from SCNB and surgical biopsies were reviewed and correlated. In 12 cases of ADH diagnosed by SCNB, surgical biopsy showed ADH in 8 (67%) cases and DCIS in the other 4 (33%) cases. In 77 cases of DCIS diagnosed by SCNB, a surgical biopsy showed DCIS in 55 (71%) cases, 6 more cases (8%) had DCIS with focal microinvasion, and 15 (19%) had invasive ductal carcinoma. In one case no residual tumor was found at surgery. In the author's patient population, the diagnosis of ADH at SCNB indicates high probability of DCIS or residual ADH in the surgical biopsy. The diagnosis of DCIS at SCNB is confirmed in the majority of surgical biopsies; however, a significant number of cases may show microinvasion or invasive carcinoma.}, } @article {pmid11348409, year = {2001}, author = {Kader, HA and Jackson, J and Mates, D and Andersen, S and Hayes, M and Olivotto, IA}, title = {Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.}, journal = {The breast journal}, volume = {7}, number = {1}, pages = {8-13}, doi = {10.1046/j.1524-4741.2001.007001008.x}, pmid = {11348409}, issn = {1075-122X}, mesh = {Adenocarcinoma/epidemiology/*pathology ; Adolescent ; Adult ; Age Distribution ; Aged ; Axilla ; Breast Neoplasms/epidemiology/*pathology ; British Columbia/epidemiology ; Carcinoma, Ductal, Breast/epidemiology/*pathology ; Case-Control Studies ; Disease-Free Survival ; Female ; Humans ; Incidence ; Lymph Nodes/*pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Neoplasm Staging ; Population Surveillance ; Probability ; Reference Values ; Retrospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan-Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients.}, } @article {pmid11348375, year = {2000}, author = {Yang, JH and Lee, SD and Nam, SJ}, title = {Diagnostic Utility of ABBI(R) (Advanced Breast Biopsy Instrumentation) for Nonpalpable Breast Lesions in Korea.}, journal = {The breast journal}, volume = {6}, number = {4}, pages = {257-262}, doi = {10.1046/j.1524-4741.2000.99105.x}, pmid = {11348375}, issn = {1524-4741}, abstract = {Introduction of mammography along with particular attention for the diagnosis and treatment of nonpalpable breast lesions has led to the development of nonresectional biopsies such as mammography-guided core needle biopsy, ultrasound-guided fine needle aspiration cytology, and localization and excisional biopsy. The Advanced Breast Biopsy Instrumentation (ABBI(R)) system, a recently developed device, has made it possible to remove a lesion completely under local anesthesia, thus providing a more reliable and rapid evaluation on an outpatient basis. We studied 159 patients with nonpalpable breast lesions from December 1996 to August 1998. Fifty-nine patients received core needle biopsies and 100 patients received excision with the ABBI system. The ABBI system patients had postexcisional mammography and specimen radiographs to confirm complete excision of the lesions. Pathologists examined permanent section specimens. In cases of malignancy, total mastectomy or reexcision was performed to secure a tumor-free margin. We collected malignant lesions in 23 of 159 patients, of whom 17 had ductal carcinoma in situ (DCIS). Postoperative histopathologic reports showed DCIS in 11 and infiltrating ductal carcinoma (IDC) in 2 among the 13 malignancies proven by stereotactic core biopsy. Among 10 malignancies proven by the ABBI system, there were 6 DCIS, 1 lobular carcinoma in situ (LCIS), and 3 IDC. In seven patients in whom mammography suggested malignancy but core biopsy showed benign lesion, localization and excisional biopsy confirmed DCIS in four of seven patients. The ABBI system is a more reliable and rapid method of evaluating breast lesions compared with stereotactic core biopsy. It is usually done under local anesthesia, minimizing the deformity of the breast. Therefore the ABBI system can be used as a preferred technique over conventional localization and excisional biopsy.}, } @article {pmid11348296, year = {1999}, author = {Fasano, M and Vamvakas, E and Delgado, Y and Inghirami, G and Mitnick, J and Roses, D and Feiner, H}, title = {Tubular Carcinoma of the Breast: Immunohistochemical and DNA Flow Cytometric Profile.}, journal = {The breast journal}, volume = {5}, number = {4}, pages = {252-255}, doi = {10.1046/j.1524-4741.1999.98103.x}, pmid = {11348296}, issn = {1524-4741}, abstract = {Molecular markers of ordinary invasive ductal carcinoma of the breast have been extensively studied and their prognostic significance has been assessed. A common variant of breast cancer, tubular carcinoma, has an excellent prognosis as judged from several clinicopathologic studies. One would assume that tubular carcinomas have "favorable" molecular markers, however, published series of tubular carcinomas do not include molecular markers. We describe the molecular markers of 39 consecutive tubular carcinomas collected between January 1995 and July 1997. DNA ploidy, S-phase, estrogen and progesterone receptor (ER and PR, respectively) expression, and immunoreactivity for MIB-1, p53, and erbB2 were evaluated. Seventy-two percent of tubular carcinomas were DNA diploid, 49% had an S-phase less than 5%, 95% were ER positive, 69% were PR positive, 88% had less than 10% MIB-1-positive cells, 97% were p53 negative, and 97% did not overexpress erbB2 protein. Thus tubular carcinomas exhibit favorable molecular characteristics, which may play a role in their good prognosis.}, } @article {pmid11348292, year = {1999}, author = {Stomper, PC and Waddell, BE and Edge, SB and Klippenstein, DL}, title = {Breast MRI in the Evaluation of Patients with Occult Primary Breast Carcinoma.}, journal = {The breast journal}, volume = {5}, number = {4}, pages = {230-234}, doi = {10.1046/j.1524-4741.1999.99004.x}, pmid = {11348292}, issn = {1524-4741}, abstract = {Occult primary breast carcinoma presenting as isolated ipsilateral axillary lymph node metastases in patients with normal mammograms and normal physical exams accounts for less than 1% of all breast carcinomas. Contrast-enhanced magnetic resonance imaging (MRI) may identify the site of primary breast carcinoma and effect management of these patients. We report on eight consecutive women evaluated in our multidisciplinary clinic who had biopsy-proven metastatic adenocarcinomas to axillary lymph nodes and occult primary carcinomas. Each patient underwent MRI at 1.5 T with a volumetric fast-spoiled gradient-echo (3D FSPGR) pulse sequence before and after injection of gadopentetate dimeglumine. Wire localization of suspicious areas of enhancement was performed under MRI or mammography guidance followed by surgical excision. Seven (88%) of the eight normal mammograms showed dense (>50%) breast parenchyma. In two (25%) of the eight patients, suspicious focal or regional enhancement was seen on MRI. Following wire localization and excision, pathologic exam showed an invasive ductal carcinoma and ductal carcinoma in situ with invasion corresponding to the MRI enhancement in the two cases. Breast MRI can identify the primary tumor site and influence management of patients presenting with clinically and mammographically occult primary breast carcinomas.}, } @article {pmid11346867, year = {2001}, author = {Sasson, AR and Fowble, B and Hanlon, AL and Torosian, MH and Freedman, G and Boraas, M and Sigurdson, ER and Hoffman, JP and Eisenberg, BL and Patchefsky, A}, title = {Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.}, journal = {Cancer}, volume = {91}, number = {10}, pages = {1862-1869}, doi = {10.1002/1097-0142(20010515)91:10<1862::aid-cncr1207>3.0.co;2-#}, pmid = {11346867}, issn = {0008-543X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma in Situ/mortality/*pathology/therapy ; Carcinoma, Lobular/mortality/*pathology/therapy ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*diagnosis ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Risk Factors ; Survival Rate ; }, abstract = {BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy.

METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years.

RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women.

CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.}, } @article {pmid11345835, year = {2001}, author = {Leong, AS and Sormunen, RT and Vinyuvat, S and Hamdani, RW and Suthipintawong, C}, title = {Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems.}, journal = {American journal of clinical pathology}, volume = {115}, number = {5}, pages = {709-718}, doi = {10.1309/wbu9-22qn-c3na-2q12}, pmid = {11345835}, issn = {0002-9173}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/classification/pathology ; Carcinoma in Situ/*chemistry/classification/pathology ; Carcinoma, Ductal, Breast/*chemistry/classification/pathology ; Cell Nucleus/pathology ; Disease Progression ; Female ; Humans ; Ki-67 Antigen/analysis ; Microfilament Proteins/analysis ; Models, Biological ; *Muscle Proteins ; Necrosis ; Neoplasm Proteins/*analysis ; Neoplasm Staging ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; }, abstract = {The relevance of 8 contemporary classification and grading systems for ductal carcinoma in situ (DCIS) of the breast was examined in 100 tumors by comparing DCIS grade with grade of the concurrent infiltrating ductal carcinoma (IDC). Besides tumor size and nodal status, the immunohistochemical parameters in both lesions were compared, including estrogen receptor, progesterone receptor, c-erbB-2 protein, E-cadherin, vimentin, Ki-67 (MIB1), and p27. Nuclear grading of DCIS alone or in combination with architectural pattern and necrosis showed the best correlation with grade of the invasive component. There also was a positive correlation between every biologic marker expressed in DCIS and in the concurrent IDC, supporting a clonal relationship. Biologic markers varied between the different grades of DCIS. DCIS is heterogeneous, and the progression of DCIS to IDC may be from low-grade DCIS to low-grade IDC and high-grade DCIS to high-grade IDC. This concept is different from the conventional model held for intraepithelial neoplasia in the cervix, vulva, vagina, and skin, in which there is increasing severity of in situ atypia (dysplasia) before the development of stromal invasion.}, } @article {pmid11345133, year = {2001}, author = {Hashimoto, K and Nio, Y and Sumi, S and Toga, T and Omori, H and Itakura, M and Yano, S}, title = {Correlation between TGF-beta1 and p21 (WAF1/CIP1) expression and prognosis in resectable invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {22}, number = {4}, pages = {341-347}, doi = {10.1097/00006676-200105000-00002}, pmid = {11345133}, issn = {0885-3177}, mesh = {Adult ; Aged ; Carcinoma, Pancreatic Ductal/*genetics/mortality/surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/*genetics ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatectomy ; Pancreatic Neoplasms/*genetics/mortality/surgery ; Prognosis ; Survival Rate ; Transforming Growth Factor beta/*genetics ; }, abstract = {Transforming growth factor-beta1 (TGF-beta1) inhibits the growth of a variety of epithelial cells; however, in many types of tumors it loses its inhibitory effect. p21(WAF1/CIP1), one of the cyclin-dependent kinase (Cdk) inhibitors induced by TGF-beta1, is considered a downstream effector of the growth-inhibitory function of TGF-beta1. We assessed the clinicopathologic significance of TGF-beta1 and p21 expression in resectable invasive ductal carcinoma (IDC) of the pancreas. Immunohistochemical examination of the expression of TGF-beta1 and p21 in 62 patients revealed positive expression of TGF-beta1 in 28 (45%) and of p21 in 25 (40%) of the 62 patients, and a significant correlation between the two expressions. The survival curve of patients with TGF-beta1(+) tumors was significantly higher than that of patients with TGF-beta1(-) tumors; p21(+) patients showed a higher survival curve than did p21(-) patients, but the difference was not statistically significant. Simultaneous analysis of TGF-beta1 and p21 expression showed that the patients with TGF-beta1(+)/p21(+) tumors had a significantly better prognosis than the others. Multivariate analysis showed that TGF-beta1 was a significantly low risk factor for death due to IDC. The concurrent evaluation of TGF-beta1 and p21 expression would be an effective tool in the prediction of the prognosis of patients with pancreatic cancer.}, } @article {pmid11343777, year = {2001}, author = {Chalmers, IJ and Aubele, M and Hartmann, E and Braungart, E and Werner, M and Höfler, H and Atkinson, MJ}, title = {Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in ductal breast cancer.}, journal = {Cancer genetics and cytogenetics}, volume = {126}, number = {1}, pages = {39-44}, doi = {10.1016/s0165-4608(00)00376-9}, pmid = {11343777}, issn = {0165-4608}, mesh = {Base Sequence ; Breast Neoplasms/*genetics/pathology ; Cadherins/*genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Deletion ; Chromosome Mapping ; *Chromosomes, Human, Pair 16 ; DNA Primers ; Humans ; Loss of Heterozygosity ; Lymphatic Metastasis ; *Multigene Family ; Repetitive Sequences, Nucleic Acid ; }, abstract = {The cadherin family of cell adhesion molecules has been implicated in tumor metastasis and progression. Eight family members have been mapped to the long arm of chromosome 16. Using radiation hybrid mapping, we have located six of these genes within a cluster at 16q21-q22.1. In invasive lobular carcinoma of the breast frequent LOH and accompanying mutation affect the CDH1 gene, which is a member of this chromosome 16 gene cluster. CDH1 LOH also occurs in invasive ductal carcinoma, but in the absence of gene mutation. The proximity of other cadherin genes to 16q22.1 suggests that they may be affected by LOH in invasive ductal carcinomas. Using the mapping data, microsatellite markers were selected which span regions of chromosome 16 containing the cadherin genes. In breast cancer tissues, a high rate of allelic loss was found over the gene cluster region, with CDH1 being the most frequently lost marker. In invasive ductal carcinoma a minimal deleted region was identified within part of the chromosome 16 cadherin gene cluster. This provides strong evidence for the existence of a second 16q22 suppressor gene locus within the cadherin cluster.}, } @article {pmid11343435, year = {2001}, author = {Subramanian, B and Axelrod, DE}, title = {Progression of heterogeneous breast tumors.}, journal = {Journal of theoretical biology}, volume = {210}, number = {1}, pages = {107-119}, doi = {10.1006/jtbi.2001.2302}, pmid = {11343435}, issn = {0022-5193}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; Disease Progression ; Female ; Humans ; Models, Biological ; }, abstract = {Two possible pathways of breast tumor progression were investigated by searching for values of transition rates that could reproduce the clinically observed co-occurrence frequencies of grades of ductal carcinoma in situ and grades of invasive ductal carcinoma in heterogeneous tumors. Two different pathways were analysed, a linear pathway with seven parameters, and a nonlinear pathway with three parameters. In each pathway ductal carcinoma in situ (DCIS) is a progenitor of invasive carcinoma (IDC). In the linear pathway breast tumor progression is along increasing grades: DCIS 1-DCIS 2-DCIS 3-IDC 1-IDC 2-IDC 3. In the nonlinear pathway progression of DCIS and progression of IDC can proceed in parallel steps, and in addition, with transitions from each grade of DCIS to a corresponding grade of IDC. The biological pathways were interpreted mathematically as compartment models with transition rates between stages in an explicit series of coupled differential equations. Two methods were used to search for transition rates that could reproduce the observed co-occurrence frequencies, a limited empirical search and an extensive genetic algorithmic search. Neither search method, with either pathway, could find a combination of transition rates that would reproduce the set of observed co-occurrence frequencies. We conclude that neither the linear pathway, nor the nonlinear pathway considered here, is an adequate description of progression in heterogeneous breast tumors. This quantitative investigation lends support to previous evidence from histopathology and molecular biology that the grades of DCIS and IDC seen together in heterogeneous breast tumors may not be obligate steps in tumor progression.}, } @article {pmid11342982, year = {2001}, author = {Yang, Q and Mori, I and Sakurai, T and Yoshimura, G and Suzuma, T and Nakamura, Y and Nakamura, M and Taniguchi, E and Tamaki, T and Umemura, T and Kakudo, K}, title = {Correlation between nuclear grade and biological prognostic variables in invasive breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {8}, number = {2}, pages = {105-110}, doi = {10.1007/BF02967488}, pmid = {11342982}, issn = {1340-6868}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/chemistry/*pathology ; Carcinoma, Ductal, Breast/chemistry/pathology ; Carcinoma, Lobular/chemistry/pathology ; Cell Nucleus/*pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {BACKGROUND: Grading of carcinomas is an estimation of differentiation. Nuclear grading is the cytological evaluation of tumor nuclei in comparison with the nuclei of normal mammary epithelial cells. Because nuclear grading does not involve an assessment of the growth pattern of the tumor, it applies not only to invasive ductal carcinoma but also to other subtypes of breast carcinoma.

METHODS: A total of 215 primary breast carcinomas obtained from the Affiliated Kihoku Hospital of Wakayama Medical College were enrolled in our present study. Nuclear grade was evaluated according to the criteria of the National Surgical Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues for all cases.

RESULTS: Thirty-two (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3. Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308, p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172, p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001).

CONCLUSIONS: These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.}, } @article {pmid11342981, year = {2001}, author = {Iwase, H and Ando, Y and Ichihara, S and Toyoshima, S and Nakamura, T and Karamatsu, S and Ito, Y and Yamashita, H and Toyama, T and Omoto, Y and Fujii, Y and Mitsuyama, S and Kobayashi, S}, title = {Immunohistochemical analysis on biological markers in ductal carcinoma in situ of the breast.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {8}, number = {2}, pages = {98-104}, doi = {10.1007/BF02967487}, pmid = {11342981}, issn = {1340-6868}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis/genetics/immunology ; Breast Neoplasms/*chemistry/classification/genetics ; Carcinoma, Ductal, Breast/*chemistry/classification/genetics ; Carcinoma, Intraductal, Noninfiltrating/*chemistry/classification/genetics ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2/genetics/immunology ; Humans ; Immunohistochemistry ; Ki-67 Antigen/analysis/immunology ; Middle Aged ; Receptors, Estrogen/analysis/immunology ; Tumor Suppressor Protein p53/analysis/immunology ; }, abstract = {BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed.

METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications.

RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis.

CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.}, } @article {pmid11341636, year = {1999}, author = {Wiley, MJ and Tran, TA}, title = {Perioperative urinary catheterisation in conjunction with epidural anaesthesia for hip and knee arthroplasty. Is it safe?.}, journal = {International journal of surgical investigation}, volume = {1}, number = {2}, pages = {157-160}, pmid = {11341636}, issn = {1028-5229}, mesh = {Aged ; Aged, 80 and over ; *Anesthesia, Epidural ; Anti-Bacterial Agents/therapeutic use ; *Arthroplasty ; Female ; Hip Joint/*surgery ; Humans ; Incidence ; Knee Joint/*surgery ; Male ; Middle Aged ; *Postoperative Care ; *Preoperative Care ; Prospective Studies ; Safety ; Urinary Catheterization/*adverse effects ; Urinary Tract Infections/epidemiology/etiology/prevention & control ; }, abstract = {The place of indwelling urinary catheterisation following epidural anaesthesia to prevent acute retention of urine after hip and knee arthroplasty is controversial. Even with the use of aseptic techniques and closed sterile drainage, bacteriuria has been reported in 10-27% of catheterised patients. A prospective trial was carried out in 68 consecutive patients undergoing knee or hip joint arthroplasty with epidural anaesthesia to investigate the perioperative complications of short term urinary catheterisation. Following establishment of combined epidural and general anaesthesia, all patients underwent urinary catheterisation under aseptic technique by a member of the surgical team. Prophylactic antibiotics were given prior to insertion and continued for 24-48h postoperatively to minimise the risk of prosthetic infection. The mean indwelling urinary catheter (IDC) period was 3.6 days (range 2-14). There were three (4.4%) urinary tract infections (UTIs) all of which resolved with appropriate antibiotics. Two were detected upon removal of the urinary catheter and one was detected on the seventh postoperative day when symptoms were detected. No patient required recatheterisation. There was no other infective morbidity or wound infection. Our findings suggest the use of IDC for short periods combined with prophylactic antibiotics is safe in the perioperative phase of joint arthroplasty.}, } @article {pmid11334657, year = {2001}, author = {Venugopalan, P and Houston, AB and Agarwal, AK}, title = {The outcome of idiopathic dilated cardiomyopathy and myocarditis in children from the west of Scotland.}, journal = {International journal of cardiology}, volume = {78}, number = {2}, pages = {135-141}, doi = {10.1016/s0167-5273(00)00480-0}, pmid = {11334657}, issn = {0167-5273}, mesh = {Adolescent ; Cardiomyopathy, Dilated/*mortality/physiopathology ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Multivariate Analysis ; Myocarditis/*mortality/physiopathology ; Retrospective Studies ; Risk Factors ; Scotland/epidemiology ; Survival Rate ; Time Factors ; }, abstract = {We analysed retrospectively all infants and children with idiopathic dilated cardiomyopathy (IDC) and myocarditis at the Regional Cardiac Centre of the Royal Hospital for Sick Children, Glasgow, during 1980-1997. Among the 39 patients with IDC, 25 (64%) were infants aged < 1 year, eight (20.5%) had wheezing as the presenting symptom, and only six (15%) had a significant cardiac murmur. Thirty-eight of thirty-nine patients diagnosed in life were followed-up for 1 day to 15 years (median 3 years). Twelve of the thirty-nine (31%) died, six deaths were within a week of presentation and the rest within a year. The survival at 1 year and at 12 years was 0.69 (95% CI 0.54 to 0.84). Fourteen patients had histologically proven myocarditis, and all 9/14 (64%) detected at post-mortem and one of the five diagnosed in life died. Patients with myocarditis exhibited an actuarial survival of 0.29 (95% CI 0.04 to 0.53) at 1 year and at 9 years, significantly lower than IDC patients (log rank 9.8, P < 0.01). There was no difference in the outcome for patients with positive or negative Coxsackie titres or who presented in the 1980s and in the 1990s. No risk factor that independently influenced the outcome or survival could be identified in either group. Thus our study from a relatively well-defined population of the west of Scotland showed that a significant proportion of children with IDC and myocarditis died in the first week of illness and that patients with myocarditis had shorter survival.}, } @article {pmid11332083, year = {2001}, author = {Lee, JS and Kim, HS and Jung, JJ and Kim, YB and Park, CS and Lee, MC}, title = {Correlation between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior.}, journal = {Analytical and quantitative cytology and histology}, volume = {23}, number = {2}, pages = {161-168}, pmid = {11332083}, mesh = {Adult ; Aged ; Analysis of Variance ; Antigens, Neoplasm/analysis ; *Apoptosis ; Breast Neoplasms/*blood supply/pathology ; Carcinoma, Ductal, Breast/*blood supply/*pathology ; Cell Division ; DNA Fragmentation ; Endothelium, Vascular/*immunology ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted/methods ; In Situ Nick-End Labeling ; Middle Aged ; *Neovascularization, Pathologic ; Proliferating Cell Nuclear Antigen/metabolism ; }, abstract = {OBJECTIVE: To investigate the relationship between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior.

STUDY DESIGN: Microvessels were immunohistochemically labeled with antibody to CD34 in sections from 82 cases of invasive ductal carcinoma. Computerized image analysis was used to evaluate microvessel density (MVD). The authors measured the apoptotic index (AI) using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling technique and proliferating cell nuclear antigen labeling index (PCNA LI) by PCNA immunohistochemistry on serial sections.

RESULTS: Statistical analysis revealed a significant inverse correlation between MVD and AI (r = -.313, P = .004) and failed to find a significant correlation between MVD and PCNA LI. There was a significant positive correlation between AI and PCNA LI (r = .393, P = .000). Significant differences in AI between high MVD (> or = 59.9%) and low MVD (< 59.9%) were seen (P < .001), with no appreciable differences in PCNA LI between the two groups. Histologic grade and stage were the only independent prognostic factors in both disease-free and overall survival.

CONCLUSION: Angiogenesis in breast cancer may be related to the ability of tumor cells to survive rather than to their proliferative activity. Apoptosis is related to cell proliferation in breast cancer.}, } @article {pmid11329139, year = {2001}, author = {Wong, SC and Chan, JK and Lee, KC and Hsiao, WL}, title = {Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast.}, journal = {The Journal of pathology}, volume = {194}, number = {1}, pages = {35-42}, doi = {10.1002/path.838}, pmid = {11329139}, issn = {0022-3417}, mesh = {Apoptosis/*physiology ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Cell Cycle Proteins/*metabolism ; Cell Division/physiology ; Cyclin D1/metabolism ; Cyclin D3 ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins/metabolism ; Disease Progression ; Female ; Humans ; In Situ Nick-End Labeling ; Microtubule-Associated Proteins/metabolism ; Neoplasm Proteins/metabolism ; *Tumor Suppressor Proteins ; }, abstract = {In order to understand the intricate relationship of cell proliferation and apoptosis in tumour development, proliferation markers (Ki-67 and c-myc), apoptosis, cell-cycle inducers cyclin D1 and D3, and cell-cycle inhibitors p16(INK4), p21(CIP1), and p27(KIP1) were evaluated in ductal breast carcinoma. The heterogeneous nature of breast tumours provides a system by which the changes in cell-cycle genes can be explored under a wide range of proliferation and apoptotic indices. To address the above issues, immunohistochemical studies were conducted in 40 pairs of tumours and adjacent normal ductal tissues. The TUNEL method was used to identify apoptotic cells. Except for p27/KIP1, the proliferation (Ki-67, c-myc) and the apoptotic indexes together with levels of p16/INK4a, p21/CIP1, cyclin D1, and cyclin D3, were clearly elevated among tumour tissues, while absent in the adjacent normal tissues. Spearman correlation analysis indicated strong associations among apoptotic index, Ki-67, c-myc, and tumour grade. In addition, p21/CIP1 and cyclin D3 were positively correlated, while p16/INK4a, p27/KIP1, and cyclin D1 were negatively correlated with tumour grade. There was clear decoupling between p21 and p27, as well as decoupling between cyclin D1 and cyclin D3, in terms of their relationship to cell proliferation and apoptosis, indicating differential roles in tumour progression.}, } @article {pmid11328317, year = {2001}, author = {El All, HA and Ismail, E and Abbas, M and Ouf, K}, title = {MIB-1 index, S-phase fraction, mitotic figure count, and SBR histologic grading in invasive breast carcinoma: a comparative study.}, journal = {The breast journal}, volume = {7}, number = {2}, pages = {106-110}, doi = {10.1046/j.1524-4741.2001.007002106.x}, pmid = {11328317}, issn = {1075-122X}, mesh = {Antigens, Nuclear ; Biopsy/standards ; Breast Neoplasms/*pathology ; *Cell Differentiation ; Egypt ; Female ; Humans ; Ki-67 Antigen ; Mitotic Index ; Nuclear Proteins ; Predictive Value of Tests ; S Phase ; }, abstract = {Proliferative activity has been proven to be of prognostic significance in breast carcinoma. This study was performed to compare the different proliferative fractions in the Egyptian population and to define the most suitable one for daily routine use in our surgical pathology laboratories. The proliferative activity of 63 invasive ductal carcinomas was evaluated by immunohistochemical staining of paraffin-embedded tissue sections with MIB-1 rabbit polyclonal antibody and the heat-induced epitope retrieval method, flow cytometric determination of the S-phase fraction (SPF) on frozen tissues, and estimation of the Scarff-Bloom-Richardson (SBR) grading and mitotic figure count (MFC) on hematoxylin and eosin-stained tissue sections. Fifty-two percent of invasive ductal carcinoma were aneuploid. The mean values of MIB-1 index, SPF, and MFC were 17.7 +/- 12.3, 4.9 +/- 3.8, and 5.2 +/- 4.5, respectively, for diploid tumors; while for aneuploid tumors, they were 58.6 +/- 31.9, 19.9 +/- 12.2, and 23.1 +/- 16.9, respectively. These values were significantly higher in aneuploid versus diploid tumors (p < 0.0001). A close correlation was found between MIB-1 index, SPF, MFC, and SBR grading (p < 0.0001). In conclusion, in surgical pathology laboratories that cannot afford the costs of flow cytometry and/or immunostaining, proper SBR grading and MFC can provide an estimation of the proliferation fraction similar to the flow cytometric SPF and MIB-1 immunostaining.}, } @article {pmid11323475, year = {2001}, author = {Vizcaíno, I and Gadea, L and Andreo, L and Salas, D and Ruiz-Perales, F and Cuevas, D and Herranz, C and Bueno, F and , }, title = {Short-term follow-up results in 795 nonpalpable probably benign lesions detected at screening mammography.}, journal = {Radiology}, volume = {219}, number = {2}, pages = {475-483}, doi = {10.1148/radiology.219.2.r01ma11475}, pmid = {11323475}, issn = {0033-8419}, mesh = {Aged ; Biopsy ; Breast Diseases/diagnosis/*diagnostic imaging ; Breast Neoplasms/diagnosis/*diagnostic imaging ; Calcinosis/diagnosis/diagnostic imaging ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; *Mammography ; Middle Aged ; Palpation ; Predictive Value of Tests ; Sensitivity and Specificity ; Ultrasonography, Mammary ; }, abstract = {PURPOSE: To evaluate short-term follow-up of nonpalpable probably benign lesions in a 2-year mammographic screening.

MATERIALS AND METHODS: Of 13,790 women aged 45-65 years who underwent first-round screening, 795 (5.8%) underwent short-term mammographic follow-up (every 6 months for 2 years) of nonpalpable probably benign lesions (eg, masses, focal asymmetric densities, and calcifications) previously assessed at an additional imaging evaluation, including ultrasonography. When no changes were found at short-term mammographic follow-up, women were assigned to the 2-year screening interval. Needle localization and surgical biopsy were performed when the lesion progressed (was enlarged or had an increased number or size of calcifications or modification of their initial characteristics). The effectiveness of this approach was evaluated with statistical analysis.

RESULTS: Of 795 lesions, 788 (99%) remained stable, and seven (1%) had changes prompting surgical biopsy. Two cancers (0.3%), one microinvasive intraductal carcinoma and one 7-mm invasive ductal carcinoma without positive nodes, were found. Four of the five benign histologic results were probably benign calcifications with progression at short-term follow-up. The sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 99%, 99%, 29%, and 100%, respectively.

CONCLUSION: The benign nature of most nonpalpable probably benign lesions can be typified with short-term mammographic follow-up. This approach permitted identification of a few low-stage carcinomas, but progression in the probably benign calcifications was usually unrelated to malignancy.}, } @article {pmid11322170, year = {2001}, author = {Rieger-Christ, KM and Pezza, JA and Dugan, JM and Braasch, JW and Hughes, KS and Summerhayes, IC}, title = {Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.}, journal = {Molecular pathology : MP}, volume = {54}, number = {2}, pages = {91-97}, pmid = {11322170}, issn = {1366-8714}, mesh = {Breast Neoplasms/*genetics/metabolism/pathology ; Cadherins/*genetics/metabolism ; Carcinoma in Situ/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; Cytoskeletal Proteins/metabolism ; Disease Progression ; Female ; Humans ; *Mutation ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; Polymorphism, Single-Stranded Conformational ; *Trans-Activators ; beta Catenin ; }, abstract = {AIMS: The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients.

METHODS: Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4-16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and beta-catenin were assessed with the use of immunohistochemistry.

RESULTS: Immunohistochemistry revealed a lack of expression of E-cadherin and beta-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, beta-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma.

CONCLUSION: These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.}, } @article {pmid11305533, year = {2001}, author = {Zecchin, M and Lenarda, AD and Bonin, M and Mazzone, C and Zanchi, C and Di Chiara, C and Davanzo, M and Scherl, G and Sabbadini, G and Sinagra, G}, title = {Incidence and predictors of sudden cardiac death during long-term follow-up in patients with dilated cardiomyopathy on optimal medical therapy.}, journal = {Italian heart journal : official journal of the Italian Federation of Cardiology}, volume = {2}, number = {3}, pages = {213-221}, pmid = {11305533}, issn = {1129-471X}, mesh = {Adult ; Age Distribution ; Aged ; Cardiomyopathy, Dilated/diagnosis/*mortality/*therapy ; *Cause of Death ; Cohort Studies ; Death, Sudden, Cardiac/*epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Probability ; Prospective Studies ; Registries ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; Sex Distribution ; Time Factors ; }, abstract = {BACKGROUND: In spite of a total mortality reduction in recent years, sudden cardiac death (SD) remains a major problem in patients with idiopathic dilated cardiomyopathy (IDC) and its occurrence is often unpredictable. Furthermore, the risk of SD may change during follow-up because of the natural history of the disease and the effects of therapeutic interventions. In our study, we evaluated the modifications of the risk of SD during follow-up in a cohort of patients with IDC and analyzed the variables predicting SD not only at enrolment but also at the last examination during optimal medical treatment.

METHODS: Since 1978, 343 consecutive patients with IDC were enrolled in the Heart Muscle Disease Registry of Trieste (Italy) and submitted to complete invasive and non-invasive study. Patients were re-evaluated usually at intervals of 12 months.

RESULTS: After a mean of 68+/-45 months, 125 events (death, heart transplantation or aborted SD) had occurred. The cumulative risk after 5 years was 30%, while after 10 years it almost doubled (54%). During the first 3 months after enrolment, the incidence of SD was high (3%). A plateau, lasting about 3.5 years, followed. A slow but progressive rise in the risk of mortality then occurred (6% at 5 years, 18% at 10 years). No variables evaluated at enrolment were associated with SD at multivariate analysis. On the other hand, the end-diastolic left ventricular diameter (> or = 38 mm/m2) and ejection fraction (< or = 0.30) were predictive of SD if evaluated within 1 year before the event. Beta-blocker treatment was associated with a non-significant reduction of risk.

CONCLUSIONS: In patients with IDC the incidence of SD progressively increased during long-term follow-up, especially in those with persistent severe left ventricular dilation and dysfunction who were not on beta-blocker treatment. Serial clinical evaluation may help to select patients at higher risk for SD.}, } @article {pmid11304577, year = {2001}, author = {Kang, JH and Kim, SJ and Noh, DY and Park, IA and Choe, KJ and Yoo, OJ and Kang, HS}, title = {Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {81}, number = {4}, pages = {573-579}, doi = {10.1038/labinvest.3780266}, pmid = {11304577}, issn = {0023-6837}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/*pathology ; CpG Islands ; *DNA Methylation ; DNA, Neoplasm/chemistry ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; *Genes, p53 ; Humans ; Mutation ; Promoter Regions, Genetic ; }, abstract = {Aberrant methylation in the CpG sites located in the promoter region of several tumor suppressor genes has been reported in various types of cancers. However, the methylation status of the p53 promoter has not been clearly determined and no information is available on its role in breast cancer. The aim of the study was to determine the presence and timing of the methylation of CpG sites in the p53 promoter, in the progression from ductal carcinoma in situ to invasive cancer. We also explored the correlation between the CpG methylation of the p53 promoter and p53 mutation during the progression of breast cancer. The corresponding lesions of both the invasive and noninvasive types were microdissected in paraffin-embedded tissue of 26 breast carcinomas. Bisulfite-modified DNA sequencing for methylation status in the p53 promoter was carried out, and double-strand DNA sequencing was performed in the promoter region and exons 4 to 9 of the p53 gene. CpG site methylation in the p53 promoter was detected in three cases (11.5%). Two noninvasive and three invasive lesions harbored CpG methylation in the p53 promoter. Methylations in more than one site were observed in three lesions, all of which contained methylation in two sites. The methylated CpG sites were located near the AP1 and YY-1 binding sites and at the YY-1 binding site. The p53 mutation was not found in the lesions where methylation in p53 promoter region was evident. In 16 cases (61.5%), neither methylation nor p53 mutation was detected. We conclude that the methylation in the p53 promoter region is found in the breast cancer irrespective of the status of invasion, and that the hypermethylation in the p53 promoter region is an alternative pathway to tumorigenesis where there is no p53 gene mutation.}, } @article {pmid11302268, year = {2001}, author = {Barber, JP and Luborsky, L and Gallop, R and Crits-Christoph, P and Frank, A and Weiss, RD and Thase, ME and Connolly, MB and Gladis, M and Foltz, C and Siqueland, L}, title = {Therapeutic alliance as a predictor of outcome and retention in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study.}, journal = {Journal of consulting and clinical psychology}, volume = {69}, number = {1}, pages = {119-124}, doi = {10.1037//0022-006x.69.1.119}, pmid = {11302268}, issn = {0022-006X}, support = {U01-DA07090/DA/NIDA NIH HHS/United States ; P30-MH-45178/MH/NIMH NIH HHS/United States ; K05-DA00168/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Cocaine-Related Disorders/*therapy ; Cognitive Behavioral Therapy/*methods ; Female ; Humans ; Male ; Odds Ratio ; Outcome and Process Assessment, Health Care ; Outpatients ; Patient Dropouts/statistics & numerical data ; Predictive Value of Tests ; *Professional-Patient Relations ; Psychiatric Status Rating Scales ; Psychotherapeutic Processes ; Psychotherapy/*methods ; Psychotherapy, Group/methods ; }, abstract = {The authors examined the relation between therapeutic alliance, retention, and outcome for 308 cocaine-dependent outpatients participating in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. High levels of alliance were observed in supportive-expressive therapy (SE), cognitive therapy (CT), and individual drug counseling (IDC), and alliance levels increased slightly but significantly from Session 2 to Session 5 in all groups. In contrast to other studies, alliance was not a significant predictor of drug outcome. However, alliance did predict patient retention differentially across the 3 treatments. In SE and IDC, either higher levels of alliance were associated with increased retention or no relationship between alliance and retention was found, depending on the time alliance was measured. In CT, higher levels of alliance were associated with decreased retention.}, } @article {pmid11301349, year = {2001}, author = {Hasebe, T and Sasaki, S and Imoto, S and Ochiai, A}, title = {Highly proliferative fibroblasts forming fibrotic focus govern metastasis of invasive ductal carcinoma of the breast.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {14}, number = {4}, pages = {325-337}, doi = {10.1038/modpathol.3880310}, pmid = {11301349}, issn = {0893-3952}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antigens, Nuclear ; Breast Neoplasms/chemistry/mortality/*pathology ; Carcinoma, Ductal, Breast/chemistry/mortality/*secondary ; Female ; Fibroblasts/chemistry/*pathology ; Fibrosis/pathology ; Humans ; Immunoenzyme Techniques ; Ki-67 Antigen/analysis ; Lymph Nodes/pathology ; Lymphatic Metastasis/*pathology ; Menopause ; Middle Aged ; Mitotic Index ; Nuclear Proteins/analysis ; Premenopause ; Survival Rate ; }, abstract = {We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCS: Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts forming FF that have positively stained nuclei, and 300 fibroblasts were counted in each FF. The significance of the proliferative activity of fibroblasts forming FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM) was compared with well-known prognostic parameters. Multivariate analysis demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The present study indicated that the metastatic ability of IDCs with FF is highly dependent on the proliferative activity of the fibroblasts forming FF.}, } @article {pmid11291923, year = {2001}, author = {Nio, Y and Iguchi, C and Yamasawa, K and Sasaki, S and Takamura, M and Toga, T and Dong, M and Itakura, M and Tamura, K}, title = {Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas.}, journal = {Pancreas}, volume = {22}, number = {3}, pages = {230-239}, doi = {10.1097/00006676-200104000-00002}, pmid = {11291923}, issn = {0885-3177}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; *Apoptosis ; Carcinoma, Pancreatic Ductal/mortality/*pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Pancreatectomy ; Pancreatic Neoplasms/mortality/*pathology/surgery ; Prognosis ; Proto-Oncogene Proteins/*analysis ; Proto-Oncogene Proteins c-bcl-2/*analysis ; Survival Rate ; bcl-2-Associated X Protein ; }, abstract = {The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis, pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI. pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.}, } @article {pmid11291709, year = {2001}, author = {Takei, H and Iino, Y and Horiguchi, J and Maemura, M and Koibuchi, Y and Yokoe, T and Morishita, Y and Jordan, VC}, title = {Tamoxifen-failed male breast cancer with a high level of circulating estrogen: report of a case.}, journal = {Surgery today}, volume = {31}, number = {2}, pages = {149-151}, doi = {10.1007/s005950170199}, pmid = {11291709}, issn = {0941-1291}, mesh = {Adult ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents, Hormonal/*pharmacology/therapeutic use ; Breast Neoplasms, Male/drug therapy/*pathology/surgery ; Carcinoma, Ductal, Breast/drug therapy/*pathology/surgery ; Drug Administration Schedule ; Drug Resistance, Neoplasm ; Drug Therapy, Combination ; Estradiol/*blood ; Fatal Outcome ; Fluorouracil/therapeutic use ; Humans ; Male ; *Neoplasm Recurrence, Local ; Tamoxifen/*pharmacology/therapeutic use ; Time Factors ; }, abstract = {We report herein the case of a 40-year-old man with grade II invasive ductal carcinoma of the breast (pT1, pN0, M0: stage I) in whom a recurrence developed shortly after completion of a 2-year course of tamoxifen and 5-fluorouracil therapy following a mastectomy. Although the metastatic tumor was estrogen receptor-positive, hormone therapy combined with chemotherapy had no significant effect on tumor growth, and the patient died from disseminated tumors 2 years 6 months after completion of the adjuvant therapy. It is noteworthy that the circulating estradiol level increased from 18.0 to 892.3 pg/ml during the period of tumor progression and dissemination. We interpret these findings as an indication of high aromatase activity in the metastatic tumors. We suggest that extending tamoxifen treatment to 5 years or longer be recommended for the standard adjuvant hormone therapy of male breast cancer to prevent the early recurrence of hormone-responsive disease.}, } @article {pmid11288957, year = {2001}, author = {Ruibal, A and Arias, JI and Del Río, MC and Lapeña, G and Schneider, J and Tejerina, A}, title = {Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients.}, journal = {The International journal of biological markers}, volume = {16}, number = {1}, pages = {56-61}, doi = {10.1177/172460080101600108}, pmid = {11288957}, issn = {0393-6155}, mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology/secondary ; Female ; Humans ; Hyaluronan Receptors/metabolism ; Hyaluronic Acid/metabolism ; Lymphatic Metastasis ; Ploidies ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; S Phase ; Tissue Plasminogen Activator/metabolism ; }, abstract = {In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.}, } @article {pmid11284955, year = {2001}, author = {Bonzanini, M and Gilioli, E and Brancato, B and Cristofori, A and Bricolo, D and Natale, N and Valentini, A and Dalla Palma, P}, title = {The cytopathology of ductal carcinoma in situ of the breast. A detailed analysis of fine needle aspiration cytology of 58 cases compared with 101 invasive ductal carcinomas.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {12}, number = {2}, pages = {107-119}, doi = {10.1046/j.1365-2303.2001.00308.x}, pmid = {11284955}, issn = {0956-5507}, mesh = {Adult ; Aged ; Biopsy, Needle ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Intraductal, Noninfiltrating/*pathology ; False Negative Reactions ; False Positive Reactions ; Female ; Humans ; Mammography ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; }, abstract = {Bonzanini M., Gilioli E., Brancato B., Cristofori A., Bricolo D., Natale N., Valentini A., and Dalla Palma P. (2001)Cytopathology 12, 107-119. The cytopathology of ductal carcinoma in situ of the breast. A detailed analysis of fine needle aspiration cytology of 58 cases compared with 101 invasive ductal carcinomas. The existence of cytological findings that discriminate ductal carcinoma in situ (DCIS) of the breast from invasive ductal carcinoma (IDC) has not been unanimously accepted and the role of fine needle aspiration cytology (FNAC) remains controversial. We report the cytological findings of a large series of FNAC from histologically proven DCIS compared with those of ductal carcinomas having a different extent of the invasive component. The association of high cohesiveness of atypical cells and absence of tubular aggregates showed good sensitivity (SE) and specificity (SP) for the diagnosis of DCIS vs IDC. The simultaneous presence of necrotic background, atypical cells with abundant eosinophilic cytoplasm and a low percentage of single malignant cells resulted in low sensitivity but high specificity and positive predictive value (PPV) for differential cytological diagnosis of DCIS vs IDC.}, } @article {pmid11284515, year = {2001}, author = {Swanson, GP and Rynearson, K and Geyer, CE and Symmonds, R and Hardin, W}, title = {Breast conservation in the treatment of breast cancer: community-based experience.}, journal = {Southern medical journal}, volume = {94}, number = {3}, pages = {287-292}, pmid = {11284515}, issn = {0038-4348}, mesh = {Breast Neoplasms/mortality/radiotherapy/*surgery ; Carcinoma, Ductal, Breast/radiotherapy/*surgery ; Community Medicine ; Female ; Follow-Up Studies ; Humans ; Mastectomy, Segmental/*methods ; Middle Aged ; Recurrence ; Survival Analysis ; Texas/epidemiology ; }, abstract = {BACKGROUND: Results of large, randomized studies in the 1980s established wide excision and radiation as an accepted breast cancer treatment approach. We evaluated our initial results with this treatment in the community setting.

METHODS: We evaluated the frequency and outcome of breast conservation treatment in 303 women with invasive ductal carcinoma from 1985 to 1995.

RESULTS: The frequency of breast conservation treatment increased from 9% during 1985 to 1989 to 24% during 1990 to 1995. With a median follow-up of 4.7 years, there were 19 (6%) ipsilateral recurrences. Metastatic disease occurred in 23 patients (8%). Overall 5-year survival was 95%, and 5-year recurrence-free survival was 90%. Twelve patients died of breast cancer.

CONCLUSIONS: Increased use of breast conservation in our community practice parallels the national trend, with similar treatment results. Our findings suggest the successful integration of research-proven innovations into community practice.}, } @article {pmid11276023, year = {2001}, author = {Nio, Y and Dong, M and Iguchi, C and Yamasawa, K and Toga, T and Itakura, M and Tamura, K}, title = {Expression of Bcl-2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: effects on clinical outcome and efficacy of adjuvant chemotherapy.}, journal = {Journal of surgical oncology}, volume = {76}, number = {3}, pages = {188-196}, doi = {10.1002/jso.1033}, pmid = {11276023}, issn = {0022-4790}, mesh = {Adult ; Aged ; Antibodies, Monoclonal ; Carcinoma, Pancreatic Ductal/*drug therapy/*metabolism/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/*metabolism/surgery ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Statistics, Nonparametric ; Treatment Outcome ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND AND OBJECTIVES: p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The Bcl-2 can work to protect cells from apoptosis, which is induced by p53 gene. These facts suggest the significant role of these genes in the genesis and progression of various tumors. The present study was designed to assess the significance of p53 and Bcl-2 protein (pBcl-2) expression on resectable invasive ductal carcinoma (IDC) of the pancreas.

METHODS: The present study included 63 IDCs, which were resected between 1982 and 1998. pBcl-2 and p53 were stained immunohistochemically with monoclonal antibodies.

RESULTS: pBcl-2 was expressed in 16 (25.4%), and p53 was positively expressed in 32 out of 63 IDCs (50.8%); however, expression of pBcl-2 did not necessarily correlate with that of p53. Although p53 expression did not show any significant influence on the patients' survival, pBcl-2(+) patients showed a higher survival than pBcl-2(-) patients for both p53(+) and p53(-) patients, which suggested that pBcl-2 expression had a more significant effect on the survival of patients than p53 expression. On the other hand, there were no differences in the survival curve between the adjuvant chemotherapy (ACT) group and the surgery alone (SA) group. pBcl-2 expression had no influence on the effect of ACT, the ACT group showed a significantly better survival than the SA group for p53(+) IDC patients.

CONCLUSIONS: pBcl-2 expression is a beneficial prognostic factor for patients with IDC, whereas p53 expression may be beneficial in the prediction of the effects of adjuvant chemotherapy on patients with IDC. J. Surg. Oncol. 2001;76:188-196.}, } @article {pmid11268786, year = {2001}, author = {Tate, PS and Rogers, EL and McGee, EM and Page, GV and Hopkins, SF and Shearer, RG and Harris, JM and Johnson, RC and Dubilier, LD and Bensema, MH and Jansen, JF and Clark, TD}, title = {Stereotactic breast biopsy: a six-year surgical experience.}, journal = {The Journal of the Kentucky Medical Association}, volume = {99}, number = {3}, pages = {98-103}, pmid = {11268786}, issn = {0023-0294}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/*methods ; Breast Diseases/diagnostic imaging/*pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Mammography ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {A retrospective review was done of all stereotactic breast biopsies performed at the Central Baptist Hospital Breast Center from February 1994 through December 1999. A total of 1,080 biopsies were performed in 1,026 patients, all by surgeons working independently. Masses were biopsied in 54% and calcifications in 40%. Eighteen percent of biopsies were malignant. The most common benign diagnosis was fibrocystic disease (72%), followed by fibroadenoma (19%), lymph node (2%), and papilloma (2%). The most common malignant diagnosis was invasive ductal carcinoma (40%) followed by ductal carcinoma in situ (32%) and mixed invasive and in situ ductal carcinoma (19%). A prebiopsy BI-RADS mammographic Category III was associated with a 2% incidence of malignancy; Category IV--17%; Category V--90%. Atypical ductal hyperplasia on stereotactic biopsy was upgraded to a malignant diagnosis after reexcision in 19% of the cases. The false-negative rate was 0.4% (sensitivity 99%) and the complication rate was 3%, mostly related to bleeding. Stereotactic biopsy is a safe and accurate technique for the minimally-invasive diagnosis of abnormal mammograms.}, } @article {pmid11267953, year = {2001}, author = {Solin, LJ and Fourquet, A and Vicini, FA and Haffty, B and Taylor, M and McCormick, B and McNeese, M and Pierce, LJ and Landmann, C and Olivotto, IA and Borger, J and de La Rochefordiere, A and Schultz, DJ}, title = {Salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ of the breast.}, journal = {Cancer}, volume = {91}, number = {6}, pages = {1090-1097}, pmid = {11267953}, issn = {0008-543X}, mesh = {Adult ; Aged ; Antineoplastic Agents, Hormonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Breast Neoplasms/*drug therapy/pathology/*surgery ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/*surgery ; Databases, Factual ; Female ; Humans ; Mammography ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/*surgery ; Retrospective Studies ; Salvage Therapy ; Survival Analysis ; Tamoxifen/administration & dosage ; Treatment Outcome ; }, abstract = {BACKGROUND: The purpose of the current study is to evaluate the outcome of salvage treatment for local recurrence after breast-conserving surgery and radiation as initial treatment for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast.

METHODS: An analysis was performed of 42 patients with local only first failure (n = 41) or local-regional only first failure (n = 1) after breast-conserving surgery and radiation treatment had been given for DCIS of the breast. Surgical treatment at the time of local recurrence included mastectomy (n = 37; 88%) or excision (n = 5; 12%). Adjuvant systemic therapy at the time of local recurrence was chemotherapy (n = 3; 7%), tamoxifen (n = 8; 19%), both (n = 1; 2%), none (n = 29; 69%), or unknown (n = 1; 2%). The median interval from the time of initial treatment to local recurrence was 4.8 years (range = 1.0-15.2 yrs). The median follow-up after salvage treatment was 4.5 years (range = 0.2-12.8 yrs).

RESULTS: At the time of the local recurrence, 22 patients (52%) had invasive ductal carcinoma, 18 patients (43%) had DCIS, 1 patient (2%) had invasive lobular carcinoma, and 1 patient (2%) had angiosarcoma. After salvage treatment, the rate of overall survival and the rate of cause specific survival for all 42 patients were 92% at both 5- and 8-years after treatment. The rate of freedom from distant metastases was 89% at 5 and 8 years. Favorable prognostic factors after salvage treatment were DCIS as the histology of the local recurrence and mammography only as the method of detection of the local recurrence.

CONCLUSIONS: The results of salvage treatment in the current study demonstrated that local recurrences were salvaged with high rates of survival and freedom from distant metastases. These results support the use of breast-conserving surgery and radiation for initial management of DCIS of the breast.}, } @article {pmid11267940, year = {2001}, author = {Ariga, N and Suzuki, T and Moriya, T and Kimura, M and Inoue, T and Ohuchi, N and Sasano, H}, title = {Progesterone receptor A and B isoforms in the human breast and its disorders.}, journal = {Japanese journal of cancer research : Gann}, volume = {92}, number = {3}, pages = {302-308}, pmid = {11267940}, issn = {0910-5050}, mesh = {Breast/cytology/*pathology ; Breast Diseases/*pathology ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/pathology ; Carcinoma, Ductal, Breast/pathology ; Estrogen Receptor alpha ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Neoplasm Invasiveness ; Receptors, Estrogen/analysis ; Receptors, Progesterone/*analysis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Two different isoforms of progesterone receptor (PR), PRA and PRB, are expressed in target tissues at comparable levels. In this study, we first examined PRA and PRB immunoreactivity in human breast cancer and various intraductal proliferative epithelial lesions, and correlated these findings with clinicopathologic parameters. We then examined mRNA expression of PRA and PRB in six cases of invasive ductal carcinoma using RT-PCR. Immunoreactivity for both PRA and PRB was positive in the great majority of proliferative disease without atypia (PDWA) (85% for PRA and 96% for PRB) and atypical ductal hyperplasia (ADH) (100% for PRA and 100% for PRB), but the ratio of immunopositive cases and immunohistochemical (IHC) scores was significantly smaller in ductal carcinoma in situ (DCIS) (65% for PRA and 75% for PRB) and invasive ductal carcinoma (IDC) (66% for PRA and 55% for PRB) than in PDWA and ADH. There was a significant positive correlation between IHC scores for PRA and estrogen receptor alpha (ERalpha) in IDC, DCIS and ADH but not between PRB and ERalpha. In IDC, both PRA and PRB IHC scores were significantly associated with histological grade, but there was no association between PRA or PRB status and lymph node involvement, tumor size, or prognosis of the patients. The expression of mRNAs for both PRA and PRB was detected in all six cases of IDC examined. These results suggest that both PRA and PRB are strongly associated with ERalpha in human breast and this relation may be disturbed in breast cancer.}, } @article {pmid11265127, year = {2001}, author = {Mizutani, Y and Yamashita, T and Sakamoto, G}, title = {[Radiation therapy for brain metastases from breast cancer by histological classification].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {61}, number = {3}, pages = {89-95}, pmid = {11265127}, issn = {0048-0428}, mesh = {Adult ; Aged ; Brain Neoplasms/pathology/*radiotherapy/*secondary ; Breast Neoplasms/*classification/*pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Analysis ; }, abstract = {One hundred thirteen patients with metastatic brain tumor from breast cancer who were treated with external irradiation between 1989 and 1997 at Cancer Institute Hospital were studied. The patients were all histopathologically proven to have invasive ductal carcinoma (scirrhous type 54 cases, papillotubular type 18, solid-tubular type 41). The patients were evaluated for efficacy and histopathological subtypes. The time interval between the diagnosis of breast cancer and brain metastases was 53.6 months for the scirrhous type, 75.0 months for the papillotubular type, and 35.5 months for the solid-tubular type. The time interval between the diagnosis of initial distant metastases and brain metastases was 14.3 months for the scirrhous type, 22.5 months for the papillotubular type, and 12.5 months for the solid-tubular type. Efficacy rates (CR + PR) for external irradiation of the brain metastases were 40.0% for the scirrhous type, 66.7% for the papillotubular type, and 36.6% for the solid-tubular type. The papillotubular type had a favorable efficacy rate compared with the other two types. Median survival time (MST) from the start of treatment for brain metastases and one-year survival rate were 5 months and 11.1% for the scirrhous type, 7 months and 41.5% for the papillotubular type, and 4 months and 28.3% for the solid-tubular type, respectively. No statistically significant difference between survival rates was observed among the histopathological types. Univariate analysis showed performance status, number of metastatic tumors, and existence of extracranial metastases without bony metastasis to be significantly related to prognosis. Multivariate analysis showed only extracranial metastases without bony metastases to be related to prognosis.}, } @article {pmid11259968, year = {2001}, author = {Cawson, JN and Law, EM and Kavanagh, AM}, title = {Invasive lobular carcinoma: sonographic features of cancers detected in a BreastScreen Program.}, journal = {Australasian radiology}, volume = {45}, number = {1}, pages = {25-30}, doi = {10.1046/j.1440-1673.2001.00867.x}, pmid = {11259968}, issn = {0004-8461}, mesh = {Australia/epidemiology ; Breast Neoplasms/*diagnostic imaging/epidemiology ; Carcinoma, Lobular/*diagnostic imaging/epidemiology ; Chi-Square Distribution ; Female ; Humans ; Mammography ; Mass Screening ; Odds Ratio ; Sensitivity and Specificity ; *Ultrasonography, Mammary ; }, abstract = {Sixty-two screen-detected invasive lobular carcinomas (ILC) were studied for sonographic, mammographic, clinical and histological findings. Ultrasound (US) features were compared with 60 invasive duct cancers (IDC). Size and axillary lymph node status in ILC were compared with all other cancers detected. In 41 ILC examined with US, 36 were found as masses (87.8% sensitivity; 95% CI 77.8-97.8%). Some US features of ILC and IDC differed: ILC were 9.94 times more likely to be hyperechoic (odds ratio, OR, 9.94; 95% CI 3.28-31.74) and 77% less likely to be taller than wide (OR 0.23; 95% CI 0.18-0.62). Thirty-three ILC showed typical malignant features of spiculate margins and acoustic shadowing. invasive lobular carcinomas had a greater mean diameter (20.4 mm; n = 60) than other invasive cancers (14.4 mm; n = 322) (P < 0.001). Ultrasound-guided needle biopsy was the method of diagnosis in 26 of 41 impalpable ILC (63%). Ultrasound has high sensitivity in characterizing screen-detected ILC, which may have atypical sonographic features including hyperechogenicity and a wider than tall shape. Ultrasound was an important contributor to diagnosis.}, } @article {pmid11259807, year = {2001}, author = {de Boer, RA and Henning, RH and Suurmeijer, AJ and Pinto, YM and Olthof, E and Kirkels, JH and van Gilst, WH and Crijns, HJ and van Veldhuisen, DJ}, title = {Early expression of natriuretic peptides and SERCA in mild heart failure: association with severity of the disease.}, journal = {International journal of cardiology}, volume = {78}, number = {1}, pages = {5-12}, doi = {10.1016/s0167-5273(00)00440-x}, pmid = {11259807}, issn = {0167-5273}, mesh = {Adult ; Aged ; Atrial Natriuretic Factor/*metabolism ; Calcium-Transporting ATPases/*metabolism ; Cardiomyopathy, Dilated/*blood/physiopathology ; Disease Progression ; Female ; *Gene Expression ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*metabolism ; RNA, Messenger/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; Severity of Illness Index ; }, abstract = {BACKGROUND: We investigated changes in genetic expression of atrial and brain natriuretic peptides (ANP and BNP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in patients with stable mild to moderate chronic heart failure (CHF), since data on this topic were primarily obtained in end-stage CHF.

METHODS: We studied tissue from 25 patients with idiopathic dilated cardiomyopathy (IDC) in New York Heart Association (NYHA) class II (n=12) and III-IV (n=13). Myocardial tissue from normal hearts (n=10) served as controls. Messenger RNA (mRNA) expression of ANP, BNP, and SERCA was isolated, and correlated with severity of CHF, left ventricular function (LVEF), peak oxygen uptake (peak VO(2)), and wedge pressure.

RESULTS: A significant trend for gradual changes in mRNA expression according to increasing NYHA class was found for ANP, BNP (P<0.0001) and SERCA (P=0.04), with a marked increase in patients with more advanced CHF (ANP and BNP: P<0.01 vs. controls; SERCA: NS) and less pronounced changes in patients with mild CHF. mRNA of ANP and BNP correlated strongly with LVEF (-0.621 and -0.621, respectively, both P<0.01) and peak VO(2) (-0.625 and -0.555, respectively, both P<0.01) and, to a lesser extent, with wedge pressure (0.440 and 0.488, respectively, both P<0.05). SERCA correlated most strongly with wedge pressure (-0.623, P<0.01), and weak, non-significant correlations with LVEF and peak VO(2) were found.

CONCLUSIONS: Genetic expression of ANP, BNP, and SERCA is progressively altered in proportion to the severity of CHF, although this is more marked for ANP and to a lesser extent BNP, than for SERCA. These changes support the concept that already early in CHF, genetic expression is affected, which has implications for the understanding of the pathophysiology of CHF.}, } @article {pmid11249077, year = {2001}, author = {Furukawa, H and Iwata, R and Moriyama, N}, title = {Is CT during arterial portography useful for the preoperative evaluation of liver metastases from pancreatic carcinoma?.}, journal = {Pancreas}, volume = {22}, number = {2}, pages = {200-202}, doi = {10.1097/00006676-200103000-00015}, pmid = {11249077}, issn = {0885-3177}, mesh = {Humans ; Liver Neoplasms/*diagnostic imaging/*secondary/surgery ; Pancreatic Neoplasms/*diagnostic imaging/surgery ; Portography ; *Tomography, X-Ray Computed ; }, abstract = {We evaluated computed tomography during arterial portography (CTAP) for the preoperative evaluation of liver metastases from pancreatic carcinoma. Thirty-one patients with invasive ductal carcinoma of the pancreas underwent CTAP for evaluation of liver metastasis. Diagnostic accuracy of CTAP was compared with that of intravenous contrast-enhanced CT (IVCT). In this series, both CTAP and IVCT showed the same diagnostic accuracy for the patients. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of both CT examinations for detecting liver metastases were 60% (three of five), 100% (26 of 26), 100% (three of three), 93% (26 of 28), and 94% (29 of 31), respectively. CTAP did not confer any advantage over IVCT for the preoperative evaluation of liver metastases from pancreatic carcinoma.}, } @article {pmid11247699, year = {2001}, author = {O'Driscoll, D and Britton, P and Bobrow, L and Wishart, GC and Sinnatamby, R and Warren, R}, title = {Lobular carcinoma in situ on core biopsy-what is the clinical significance?.}, journal = {Clinical radiology}, volume = {56}, number = {3}, pages = {216-220}, doi = {10.1053/crad.2000.0615}, pmid = {11247699}, issn = {0009-9260}, mesh = {Aged ; Biopsy ; Breast Neoplasms/*diagnosis/surgery ; Carcinoma in Situ/*diagnosis/surgery ; Carcinoma, Ductal, Breast/*diagnosis/surgery ; Carcinoma, Lobular/*diagnosis/surgery ; Female ; Humans ; Mammography ; Mass Screening/*methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Stereotaxic Techniques ; }, abstract = {AIM: To retrospectively review the surgical histological findings in all cases where lobular carcinoma in situ(LCIS) was identified on percutaneous core biopsy (CB) performed as part of the Cambridge and Huntingdon breast screening programme.

MATERIALS AND METHODS: We retrospectively reviewed all the core biopsies performed in our department for screen detected abnormalities over a 5-year period between 1 April 1994 and 31 March 1999. All patients where LCIS was identified on CB were reviewed. As the significance of LCIS on CB was unclear all went on to surgical excision. We reviewed the clinical and imaging findings, biopsy technique and subsequent surgical histology of each patient.

RESULTS: During the study period 60 769 women were invited for screening, of whom 47 975 attended (attendance rate = 79%). Of these, 2330 (4.9%) were recalled for assessment and 749 (1.6%) underwent CB. A malignant diagnosis was obtained in 311 (42%), 211 invasive and 100 in situ lesions. LCIS was identified on CB in 13 (2%). LCIS was the only lesion identified in seven cases. All seven cases subsequently underwent surgical excision. Surgical histology revealed a single case of LCIS and invasive lobular carcinoma. There were two cases of LCIS and DCIS one with a probable focus of invasive ductal carcinoma. In one case LCIS was identified in association with a radial scar. In three of the seven cases LCIS was the only abnormality on both CB and surgical biopsy.

CONCLUSION: Our series shows that isolated LCIS on CB following mammographic screening is an infrequent finding, and it may be associated with either an invasive cancer or DCIS. It is therefore advisable that when LCIS is identified on CB, surgical excision of the mammographic abnormality should be performed. Decisions on management should be undertaken in a multidisciplinary setting taking into account clinical and imaging findings.}, } @article {pmid11247396, year = {2000}, author = {Rudnicka, L and Stachura, J}, title = {Correlation between type and grade of ductal carcinoma in situ and concomitant invasive ductal carcinoma of the breast.}, journal = {Polish journal of pathology : official journal of the Polish Society of Pathologists}, volume = {51}, number = {3}, pages = {137-143}, pmid = {11247396}, issn = {1233-9687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*pathology ; Calcinosis/pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; }, abstract = {Morphological analysis was made in a group of 52 breast cancers, in which ductal carcinoma in situ (DCIS) was coexisted with invasive ductal carcinoma. DCIS was graded according to the cytological, Van Nuys and Holland classifications sharing a criterion of evaluating the degree of cancer cell nuclear atypia, and the histological classification. Histological grading of invasive breast carcinoma was based upon the modified Bloom and Richardson classification. Statistical analysis revealed a significant correlation between grades of invasive carcinoma and concomitant DCIS. This indicates a high prognostic value of above-mentioned DCIS classifications, proving their clinical usefulness. The Van Nuys classification should be recommended as its criteria are precise and there is no need to isolate DCIS with intermediate nuclear atypia, which improves assessment of the lesion.}, } @article {pmid11244947, year = {1998}, author = {Zhang, T and Tu, X and Xu, W}, title = {[A study of prognostic factors in breast cancer: histological grading].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {27}, number = {6}, pages = {405-407}, pmid = {11244947}, issn = {0529-5807}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Follow-Up Studies ; Humans ; Neoplasm Staging ; Survival Rate ; }, abstract = {OBJECTIVE: To study the significance of histological grading as a prognostic factor in breast cancer.

METHODS: According to the grading systems of Bloom-Richardson and Elston, 476 cases of invasive ductal carcinoma (IDC) with more than 5 year follow-up were assessed for grade I (GI, 72 cases), grade II (G II, 216 cases) and grade III (G III, 188 cases).

RESULTS: The 5 year survival rate for IDC G I, G II and G III were 81.9% (59 cases), 63.4% (137 cases) and 49.5% (93 cases) respectively.

CONCLUSION: Histological grading of IDC is as good a prognostic factor as their clinical stage.}, } @article {pmid11241314, year = {2001}, author = {Ariga, N and Sato, E and Ohuchi, N and Nagura, H and Ohtani, H}, title = {Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast.}, journal = {International journal of cancer}, volume = {95}, number = {1}, pages = {67-72}, doi = {10.1002/1097-0215(20010120)95:1<67::aid-ijc1012>3.0.co;2-u}, pmid = {11241314}, issn = {0020-7136}, mesh = {Breast Neoplasms/*enzymology/*mortality ; Carcinoma, Ductal, Breast/*enzymology/*mortality ; Cell Membrane/*enzymology ; Disease-Free Survival ; Endopeptidases ; Female ; Fibroblasts/enzymology ; Gelatinases/*biosynthesis ; Humans ; Immunohistochemistry ; Keratins/biosynthesis ; Lymphatic Metastasis ; *Membrane Proteins ; Microscopy, Fluorescence ; Multivariate Analysis ; Procollagen/biosynthesis ; Prognosis ; Proportional Hazards Models ; Serine Endopeptidases/*biosynthesis ; Stromal Cells/*enzymology ; Time Factors ; }, abstract = {Fibroblast activation protein (FAP)/seprase is a serine integral membrane proteinase with gelatinase activity, which is expressed by activated fibroblasts in the stroma of various epithelial cancers, mesenchymal tumors and breast-cancer cells, as well as during wound repair. However, the pathophysiologic significance of its expression remains poorly understood. The present study was designed to reveal the impact of stromal expression of FAP/seprase on survival in human breast cancer. Immunohistochemical expression of FAP/seprase was restricted to stromal fibroblasts adjacent to tumor-cell nests but not cancer cells, which was confirmed by double-labeling immunohistochemistry. Clinicopathologic analysis revealed that more abundant FAP/seprase expression in 112 cases of invasive ductal carcinoma is associated with longer overall and disease-free survival. Multivariate analysis with other clinicopathologic factors demonstrated that FAP/seprase expression is an independent prognostic factor. The effect on the survival rate of FAP/seprase was also apparent in cases with lymph node metastasis. FAP/seprase expression is one of the manifestations of the stromal reaction (i.e., matrix turnover); thus, invasive ductal carcinomas with fewer stromal reactions expressing FAP/seprase may be more aggressive.}, } @article {pmid11238620, year = {2001}, author = {Bakri, Y and Schiffer, C and Zennou, V and Charneau, P and Kahn, E and Benjouad, A and Gluckman, JC and Canque, B}, title = {The maturation of dendritic cells results in postintegration inhibition of HIV-1 replication.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {166}, number = {6}, pages = {3780-3788}, doi = {10.4049/jimmunol.166.6.3780}, pmid = {11238620}, issn = {0022-1767}, mesh = {Active Transport, Cell Nucleus/immunology ; Antigens, CD34/biosynthesis ; Antiviral Agents/*immunology ; Cell Differentiation/immunology ; Cell Nucleus/immunology/metabolism/virology ; Cells, Cultured ; DNA, Viral/antagonists & inhibitors/metabolism ; Dendritic Cells/*cytology/enzymology/immunology/*virology ; Down-Regulation/immunology ; HIV Long Terminal Repeat/immunology ; HIV-1/growth & development/immunology/*physiology ; Hematopoietic Stem Cells/cytology/immunology/virology ; Humans ; Monocytes/cytology/immunology/virology ; Polymerase Chain Reaction ; Reverse Transcriptase Inhibitors/immunology ; Transcription, Genetic/immunology ; Virus Integration/*immunology ; Virus Replication/*immunology ; }, abstract = {Maturation of dendritic cells (DC) is known to result in decreased capacity to produce HIV due to postentry block of its replicative cycle. In this study, we compared the early phases of this cycle in immature DC (iDC) and mature DC (mDC) generated from monocytes cultured with GM-CSF and IL-4, trimeric CD40 ligand (DC(CD40LT)), or monocyte-conditioned medium (DC(MCM)) being added or not from day 5. Culture day 8 cells exposed to X4 HIV-1(LAI) or R5 HIV-1(Ba-L) were analyzed by semiquantitative R-U5 PCR, which detects total HIV DNA. CXC chemokine receptor 4(low) (CXCR4(low)) CCR5(+) iDC harbored similar viral DNA amounts when exposed to either strain. HIV-1(LAI) entered more efficiently into DC(CD40LT) or DC(MCM) with up-regulated CXCR4. CCR5(low) DC(CD40LT) still allowed entry of HIV-1(Ba-L), whereas CCR5(-) DC(MCM) displayed reduced permissivity to this virus. Comparing amounts of late (long terminal repeat (LTR)-gag PCR) and total (R-U5 PCR) viral DNA products showed that HIV-1(Ba-L) reverse transcription was more efficient than that of HIV-1(LAI), but was not affected by DC maturation. Southern blot detection of linear, circular, and integrated HIV DNA showed that maturation affected neither HIV-1 nuclear import nor integration. When assessing virus transcription by exposing iDC to pNL4-3.GFP or pNL4-3.Luc viruses pseudotyped with the G protein of vesicular stomatitis virus (VSV-G), followed by culture with or without CD40LT or MCM, GFP and luciferase activities decreased by 60-75% in mDC vs iDC. Thus, reduced HIV replication in mDC is primarily due to a postintegration block occurring mainly at the transcriptional level. We could not relate this block to altered expression and nuclear localization of NF-kappa B proteins and SP1 and SP3 transcription factors.}, } @article {pmid11237487, year = {2001}, author = {Jenkinson, AD and Al-Mufti, RA and Mohsen, Y and Berry, MJ and Wells, C and Carpenter, R}, title = {Does intraductal breast cancer spread in a segmental distribution? An analysis of residual tumour burden following segmental mastectomy using tumour bed biopsies.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {27}, number = {1}, pages = {21-25}, doi = {10.1053/ejso.2000.1051}, pmid = {11237487}, issn = {0748-7983}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Biopsy ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/pathology/*surgery ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm, Residual ; }, abstract = {INTRODUCTION: Breast-conserving surgery for early breast cancer is now routinely used as an alternative to mastectomy. Despite post-operative radiotherapy, early local recurrence of tumour remains a concern. It has been reported that invasive and in-situ ductal carcinoma spread locally through the ductal tree in a segmental distribution, however, there is no consensus as to the best surgical method to maximize tumour clearance whilst leaving a good cosmetic result.

AIM: We aimed to measure the effectiveness of segmental mastectomy (excision of tumour plus associated segmental ductal tissue) in the clearance of different tumour types. Bed biopsy of the excision cavity was employed to assess the rate of incomplete excision or the multifocality of certain breast cancers.

METHODS: One hundred and one patients with breast cancers underwent segmental mastectomy and cavity bed biopsies. Specimens were assessed for tumour type and completeness of excision. An excision of the cancer was considered incomplete if the margins were involved or if any of the bed biopsies showed residual or multifocal tumour.

RESULTS: A total of 24 patients had incomplete tumour excision. Invasive ductal carcinoma was more likely to be completely excised by segmental mastectomy than invasive lobular carcinoma (P<0.05). Incomplete excision was associated with multifocality and the presence of extensive DCIS. The report of clear pathological margins was significantly more likely to be accurate, as measured by negative bed biopsies, in invasive ductal carcinoma when compared to invasive lobular carcinoma (P<0.05).

CONCLUSION: These results support the concept that ductal carcinomas spread locally in a segmental fashion. Patients with invasive ductal carcinomas are more likely to benefit from breast conserving surgery that is tailored to include the associated ductal tissue, in a segmental fashioned excision.}, } @article {pmid11233739, year = {2001}, author = {Sağol, O and Culhaci, N and Yörükoğlu, K and Ozen, E and Canda, T}, title = {Quantification of tumor cellularity and mitotic index in invasive ductal carcinoma of the breast.}, journal = {Analytical and quantitative cytology and histology}, volume = {23}, number = {1}, pages = {21-26}, pmid = {11233739}, mesh = {Breast Neoplasms/*pathology/ultrastructure ; Carcinoma, Ductal, Breast/*pathology/ultrastructure ; Cell Count/*methods ; Humans ; *Mitotic Index ; Observer Variation ; }, abstract = {OBJECTIVE: To evaluate the use of stereologically estimated tumor cell counts in the mitotic index as well as to investigate its correlation with the currently used method and test the reproducibility of the method.

STUDY DESIGN: The stereologic method described by Simpson et al was used to estimate tumor cellularity in 50 invasive ductal carcinomas. Mitotic counts were also performed, and the mitotic index was calculated by the use of estimated tumor cell counts. Estimated cell counts and the mitotic index calculated were compared statistically with the actual cell counts and the traditional mitotic grades, respectively. Interobserver reproducibility of the method was also tested.

RESULTS: Stereologically estimated tumor cell counts had a good correlation with actual cell counts (r = .891, P < .001). Besides, the mitotic indices calculated with tumor cell counts (calculated with both estimated and actual cell counts) in the denominator of the fraction of the mitotic index were in agreement with the currently used method (P < .01 for both). There was no statistically significant difference between the counts of two observers (P = .068).

CONCLUSION: The suggested method, considering tumor cellularity as an influencing factor, was practical, reproducible and in agreement with the traditional method. This method should be studied in a large group of patients with follow-up data to determine the threshold values for different grades and determine its prognostic value during the disease course.}, } @article {pmid11233548, year = {2001}, author = {Krausz, Y and Ikeda, DM and Jadvar, H and Langleben, D and Birdwell, R and Strauss, HW}, title = {Non-visualization of sentinel lymph node in patients with breast cancer.}, journal = {Nuclear medicine communications}, volume = {22}, number = {1}, pages = {25-32}, doi = {10.1097/00006231-200101000-00004}, pmid = {11233548}, issn = {0143-3636}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Breast Neoplasms/*diagnostic imaging/pathology ; Female ; Humans ; Logistic Models ; Lymph Nodes/*diagnostic imaging/pathology ; Middle Aged ; Radionuclide Imaging ; Radiopharmaceuticals ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Technetium Tc 99m Sulfur Colloid ; }, abstract = {Histological evaluation of the first draining lymph node (sentinel node) in the axilla of patients with breast cancer has dramatically altered the surgical approach to these patients, with sparing of the axilla if no tumour cells are identified. In a fraction of patients imaged after peri-tumoural injection of the breast, there is no visualization of the sentinel node. We retrospectively analysed the status of patients whose nodes were visualized and of patients whose nodes failed to visualize, to define the variables associated with non-visualization of the sentinel node. Seventy-four breast cancer patients were imaged following peri-tumoural injection of filtered 99Tc(m)-sulfur colloid, immediately and up to 5.5 h post-injection. The scintigraphic data were analysed with reference to the patient's age, histology, grade, site and size of tumour, previous diagnostic procedure and time interval to scan, using univariate analysis and a logistic regression model. A sentinel node was visualized in 53 of 74 women (72%). Comparison of patients with non-visualized versus visualized sentinel nodes disclosed no statistically significant univariate relation to age of the patients (P = 0.10), size of tumour (P = 0.46), site (P = 0.26), histology [invasive ductal carcinoma in 16 of 20 (80%) non-visualized cases, and in 43 of 53 (81%) visualized patients], prior excision biopsy (P = 0.36) and time interval to surgery (P = 0.29). Tumour grade was the only significant variable on univariate analysis (P = 0.03), though multivariate analysis showed that none of the independent parameters were statistically significant. In 39 patients with an upper outer quadrant tumour, the location of the sentinel node was not limited to the axilla and even crossed the midline of the breast. Our results show that none of the independent variables is associated with non-visualization of sentinel lymph node on preoperative lymphoscintigraphy of patients with breast cancer, though the tumour grade may have contributed to non-visualization of this node. The non-axillary drainage from upper outer quadrant tumours suggests the routine use of lymphoscintigraphy prior to axillary dissection.}, } @article {pmid11230710, year = {2001}, author = {Waldman, FM and Hwang, ES and Etzell, J and Eng, C and DeVries, S and Bennington, J and Thor, A}, title = {Genomic alterations in tubular breast carcinomas.}, journal = {Human pathology}, volume = {32}, number = {2}, pages = {222-226}, doi = {10.1053/hupa.2001.21564}, pmid = {11230710}, issn = {0046-8177}, support = {CA 44768/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/chemistry/*genetics/pathology ; Breast Neoplasms/chemistry/*genetics/pathology ; Cadherins/analysis ; DNA, Neoplasm/analysis ; Dissection ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Laser Therapy ; Micromanipulation ; Middle Aged ; *Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers.}, } @article {pmid11221991, year = {2001}, author = {Luppi, P and Licata, A and Haluszczak, C and Rudert, WA and Trucco, G and McGowan, FX and Finegold, D and Boyle, GJ and Trucco, M}, title = {Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of autoimmunity}, volume = {16}, number = {1}, pages = {3-13}, doi = {10.1006/jaut.2000.0462}, pmid = {11221991}, issn = {0896-8411}, mesh = {Antigens, Viral/analysis ; CD4 Antigens/biosynthesis ; CD8 Antigens/biosynthesis ; Cardiomyopathy, Dilated/*immunology/pathology/virology ; Cytokines/*genetics ; Enterovirus B, Human/genetics/immunology ; Gene Expression ; HLA-DQ Antigens/classification ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; Histocompatibility Testing ; Humans ; Immunoenzyme Techniques ; Interferon-gamma/genetics ; Interleukin-1/genetics ; Interleukin-2/genetics ; Interleukin-4/genetics ; Interleukin-6/genetics ; Leukocytes, Mononuclear/immunology ; Myocarditis/immunology ; Myocardium/immunology/pathology ; Picornaviridae/genetics/isolation & purification ; RNA, Messenger ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.}, } @article {pmid11216956, year = {2001}, author = {Iwata, M and Yoshikawa, T and Baba, A and Anzai, T and Mitamura, H and Ogawa, S}, title = {Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy.}, journal = {Journal of the American College of Cardiology}, volume = {37}, number = {2}, pages = {418-424}, doi = {10.1016/s0735-1097(00)01109-8}, pmid = {11216956}, issn = {0735-1097}, mesh = {Adult ; Aged ; Autoantibodies/*blood ; Cardiomyopathy, Dilated/epidemiology/*immunology ; Death, Sudden, Cardiac/epidemiology/*etiology ; Extracellular Matrix/immunology ; Female ; Heart Ventricles/immunology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Receptors, Adrenergic, beta-1/*immunology ; Tachycardia, Ventricular/*immunology/mortality ; }, abstract = {OBJECTIVES: We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta1-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC).

BACKGROUND: Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta1-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder.

METHODS: Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta1-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis.

RESULTS: Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <30% (p = 0.001).

CONCLUSIONS: Autoantibodies directed against the second extracellular loop of beta1-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC.}, } @article {pmid11212228, year = {2001}, author = {Shirakawa, K and Tsuda, H and Heike, Y and Kato, K and Asada, R and Inomata, M and Sasaki, H and Kasumi, F and Yoshimoto, M and Iwanaga, T and Konishi, F and Terada, M and Wakasugi, H}, title = {Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.}, journal = {Cancer research}, volume = {61}, number = {2}, pages = {445-451}, pmid = {11212228}, issn = {0008-5472}, mesh = {Angiogenesis Inducing Agents/genetics/metabolism ; Animals ; Breast Neoplasms/genetics/metabolism/*pathology ; Cadherins/genetics/metabolism ; Cell Division ; Cytokines/genetics/metabolism ; Endothelium, Vascular/*pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrosis ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Integrins/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Middle Aged ; Necrosis ; Neoplasm Transplantation ; RNA, Messenger/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Receptor, TIE-2 ; Receptors, Growth Factor/genetics/metabolism ; Receptors, Vascular Endothelial Growth Factor ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous/pathology ; Tumor Cells, Cultured/metabolism/ultrastructure ; }, abstract = {We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.}, } @article {pmid11201116, year = {2000}, author = {Mizumoto, R and Hamada, T}, title = {[Carcinoma of the pancreatic head].}, journal = {Nihon Geka Gakkai zasshi}, volume = {101}, number = {12}, pages = {869-876}, pmid = {11201116}, issn = {0301-4894}, mesh = {Anastomosis, Surgical/methods ; Choledochostomy ; Humans ; Pancreas/*surgery ; Pancreatic Neoplasms/*surgery ; Stomach/surgery ; }, abstract = {Focusing mainly on invasive ductal carcinoma of the pancreas, the history of radical surgery for this type of cancer is reviewed, including pancreatoduodenectomy, total pancreatectomy, extended radical surgery with main vascular resection and extended lymphadenectomy/retroperitoneal soft-tissue clearance, pylorus-preserving pancreaticoduodenectomy. In addition, duodenum-preserving pancreatic head resection, which has recently attracted attention in this field, as an operative technique for less-malignant, noninvasive intraductal papillary adenocarcinoma is also reviewed.}, } @article {pmid11197980, year = {2001}, author = {Lotze, U and Kaepplinger, S and Kober, A and Richartz, BM and Gottschild, D and Figulla, HR}, title = {Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {42}, number = {1}, pages = {49-54}, pmid = {11197980}, issn = {0161-5505}, mesh = {*3-Iodobenzylguanidine ; Adrenergic beta-Antagonists/*therapeutic use ; Cardiomyopathy, Dilated/*diagnostic imaging/*drug therapy ; Female ; Follow-Up Studies ; Heart/diagnostic imaging/*innervation ; Humans ; *Iodine Radioisotopes ; Male ; Middle Aged ; Myocardium/metabolism ; Prospective Studies ; Radiopharmaceuticals ; Sympathetic Nervous System/*physiopathology ; Technetium Tc 99m Sestamibi ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; }, abstract = {UNLABELLED: In chronic heart failure, elevated plasma norepinephrine (NE) levels and a disparity between the neuronal release and the effective reuptake of NE lead to an increased concentration of NE in the presynaptic cleft, causing a downregulation of the myocardial beta-adrenoceptors. The clinical and prognostic effectiveness of beta-blocker therapy has been shown in patients with chronic heart failure in several large trials. The purpose of this study was to investigate the effect of long-term beta-blocker therapy on the cardiac adrenergic nervous system as assessed by the myocardial uptake of 123I-metaiodobenzylguanidine (MIBG), an analog of NE, in idiopathic dilated cardiomyopathy (IDC).

METHODS: In 10 patients with IDC and stable chronic heart failure the myocardial MIBG uptake was measured at baseline and at 1 y (median, 11.5 mo) after treatment with beta-blockers (metoprolol, n = 5; bisoprolol, n = 1; and carvedilol, n = 4) in addition to standard medication. In parallel with the changes in MIBG uptake, the New York Heart Association functional class, the left ventricular ejection fraction (LVEF), and the left ventricular end-diastolic diameter (LVEDD) were documented before and after 1 y of therapy with beta-blockers.

RESULTS: During the 1-y follow-up, a significant increase in myocardial 123I-MIBG uptake (P = 0.005) in parallel with an improved LVEF (P = 0.005) and a reduced LVEDD (P = 0.019) was found. A trend toward an improvement of the New York Heart Association functional class under the beta-blocker therapy (P = 0.139) was also found.

CONCLUSION: Assessment of the myocardial 123I-MIBG uptake is a useful noninvasive tool for evaluating changes in cardiac sympathetic nerve activity under medical therapy. Long-term treatment with beta-blockers in IDC causes a recovery of the cardiac adrenergic nervous system concomitantly with a clinical and hemodynamic improvement.}, } @article {pmid11177649, year = {2000}, author = {Jamali, F and Sattari, S}, title = {High performance liquid chromatographic determination of cyclooxygenase II inhibitor rofecoxib in rat and human plasma.}, journal = {Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques}, volume = {3}, number = {3}, pages = {312-317}, pmid = {11177649}, issn = {1482-1826}, mesh = {Animals ; Chromatography, High Pressure Liquid/*methods ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/*blood ; Drug Stability ; Humans ; Isoenzymes/antagonists & inhibitors ; Lactones/*blood ; Male ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases ; Rats ; Rats, Sprague-Dawley ; Reference Standards ; Reproducibility of Results ; Sulfones ; }, abstract = {Rofecoxib is a relatively new non-steroidal anti-inflammatory drug with high selectivity in cyclooxygenase 2 inhibitory activity. There is only one assay reported for determination of the drug in biological samples. The assay requires a post-column UV reactor for photocyclization before detection with fluorescence detector. In addition, the internal standard (IS) used in the assay in not commercially available. We developed a new assay for determination of rofecoxib. Rat blank plasma (200 microL) or human blank plasma (500 microL) was spiked with rofecoxib to make final concentrations of 10 to 3000 ng/mL, and 100 microl of a 2 microg/mL of ketoprofen as IS, 100 microl of a pH 4.5 acetate buffer, and 6 mL of ethyl acetate were added. The resultant was vortex-mixed for 90 seconds and centrifuged at 2500 g for 3 min. The organic layer was separated and evaporated to dryness under vacuum. The residues were reconstituted in 170 microL of mobile phase and 150 microL was injected into an HPLC consisting of an autoinjector, an isocratic pump, a 10 cm 4.6 i.d. C(18) analytical column packed with 5 microm reversed phase particles, a variable UV spectrophotometer detector set at 272 nm, and an integrator. The mobile phase consisted of water (77%), acetonitrile (23%), acetic acid (0.1%), and triethylamine (0.03%) and was pumped at 1 mL/min at ambient temperature. The drug and IS were eluted at 13 and 24 min, respectively. The peak drug/IS area ratio versus drug concentrations relationship was linear (r>0.99). The extraction efficiency was >87%. The minimum quantifiable concentration was set at 10 ng/mL (correlation coefficient of <10%). This convenient, sensitive, and simple method is suitable to pharmacokinetic studies of rofecoxib in rats and humans.}, } @article {pmid11175617, year = {2001}, author = {Ferrini, FS and Rossi, MA and Neto, MM and Soares, FA}, title = {Schirrous invasive ductal carcinoma of the breast overexpress p53 oncoprotein.}, journal = {Sao Paulo medical journal = Revista paulista de medicina}, volume = {119}, number = {1}, pages = {4-6}, doi = {10.1590/s1516-31802001000100002}, pmid = {11175617}, issn = {1516-3180}, mesh = {Adult ; Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Female ; Humans ; Mutation ; Receptor, ErbB-2/genetics/*metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Receptors, Steroid/genetics/*metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {CONTEXT: Breast cancer is the most important neoplasm in adult women, and its worldwide incidence is growing. The tumoral stroma is very important for modulating the growth and invasion of the tumor itself. The relationship between these two components is not completely understood. Schirrous carcinoma is a variant of ductal invasive carcinoma in which the stroma is very desmoplastic, and the importance of this finding still a motive for debate in the literature.

OBJECTIVE: To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells.

TYPE OF STUDY: Retrospective study.

SETTING: Cancer Hospital A C Camargo and Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

SAMPLE: 107 adult women operated because of ductal invasive carcinoma. The cases were separated into 4 groups according to the desmoplastic reaction - less than 15 per cent, between 15-50 per cent, 51-85 per cent, and more than 85 per cent fibrosis. The grade of fibrosis was determined by picrus-sirius staining and quantified by using a microscope with a stereo-imaging grid. Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein.

MAIN MEASUREMENTS: Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53.

RESULTS: The results showed that schirrous carcinoma expresses oncoprotein p53 more frequently than other carcinomas with less extensive desmoplastic reaction. There were no differences between the grade of fibrosis and the other biological markers.

CONCLUSION: The intense stromal reaction in invasive ductal carcinoma may modulate the expression of p53. Further investigations should be made with the aim of understanding how this expression determines the proliferative activity in schirrous carcinoma, and whether this overexpression is secondary to mutation of the p53 gene or due to modulation of other molecules of the stroma.}, } @article {pmid11173657, year = {2000}, author = {Rehman, S and Crow, J and Revell, PA}, title = {Bax protein expression in DCIS of the breast in relation to invasive ductal carcinoma and other molecular markers.}, journal = {Pathology oncology research : POR}, volume = {6}, number = {4}, pages = {256-263}, pmid = {11173657}, issn = {1219-4956}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Cell Cycle Proteins/metabolism ; *Drosophila Proteins ; ErbB Receptors/metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Middle Aged ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; *Transcription Factors ; Tumor Suppressor Protein p53/metabolism ; bcl-2-Associated X Protein ; }, abstract = {This study describes the incidence of Bax protein expression in a series of 106 cases of breast cancer including 56 cases of ductal carcinoma in situ (DCIS) and 50 cases of invasive ductal carcinoma (IDC). Relationships of Bax expression to the histological grades of DCIS & IDC, and to the expression of Ki67, ER, p53, cerbB2 & Bcl2 are described. The expression of Bax, Ki67, ER, p53, cerbB2 and Bcl2 proteins is determined immunohistochemically. Cases were regarded positive for Bax, Bcl2 and cerbB2 when they showed either moderate or strong staining for these markers. The nuclear stains (Ki67, ER, and p53) were quantified in terms of percentage positive cells and cases for ER and p53 were considered positive when more than 10% cells were labelled. DCIS were graded histologically as well (n=18), intermediately (n=18), and poorly differentiated (n=20) Invasive ductal carcinoma was graded as grade I (well-differentiated) n=7, grade II (intermediate) n=24 and grade III (poorly differentiated) n=19. 65/106 cases (61%) were Bax positive including 37/56 (66%) of DCIS and 28/50 (56%) of IDC. Bax expression did not correlate to increasing histological grades of either DCIS or IDC. It did not correlate to Ki67, ER, p53 or cerbB2 but positive correlation was seen with Bcl2 (p=0.003). Bcl2 immunostaining displayed a negative correlation with increasing histological grades both of DCIS and IDC (p=0.026), (p=0.041) respectively. There was a trend of negative correlation of Bcl2 with Ki67 (p=0.062). It correlated positively with Bax (p=0.003) and ER (p<0.0001). Results suggest that the regulation of apoptosis is important in ductal carcinoma in situ of the breast as well as invasive ductal carcinomas. Bcl2 is associated with good prognostic markers in both DCIS and IDC, whereas the regulation of Bax is complex and does not necessarily correlate with mutant p53.}, } @article {pmid11170188, year = {2001}, author = {Blaivas, JG and Groutz, A and Verhaaren, M}, title = {Does the method of cystometry affect the incidence of involuntary detrusor contractions? A prospective randomized urodynamic study.}, journal = {Neurourology and urodynamics}, volume = {20}, number = {2}, pages = {141-145}, doi = {10.1002/1520-6777(2001)20:2<141::aid-nau16>3.0.co;2-p}, pmid = {11170188}, issn = {0733-2467}, mesh = {Aged ; Female ; Humans ; Incidence ; Male ; Muscle Contraction/*physiology ; Muscle, Smooth/*physiology ; Prospective Studies ; *Urodynamics ; }, abstract = {The International Continence Society (ICS) defines overactive detrusor as "one that is shown objectively to contract during the filling phase while the patient is attempting to inhibit micturition." The aim of the present study was to assess whether instructing the patient neither to try void nor to inhibit micturition during filling cystometry may improve the detection rate of involuntary detrusor contractions (IDCs). Forty-two consecutive patients (mean age 65 +/- 13.5 years), referred for urodynamic evaluation of persistent irritative lower urinary tract symptoms were prospectively enrolled. All patients were presumed, by history, to have IDCs. Cystometry was performed twice at the same session, each time by using randomly different instructions: Method 1, patients were instructed to try to inhibit micturition during bladder filling; and Method 2, patients were instructed to neither try to void nor try to inhibit micturition, but simply report his or her sensations to the examiner. The occurrence, as well as the urodynamic characteristics of IDCs, were analyzed separately and compared between the two filling methods. Method 1 identified only 20 cases of IDCs, while Method 2 identified 27 cases (48 versus 64 % of the study population, respectively; P = 0.02). Analysis of urodynamic characteristics revealed a clear trend of reduced bladder volume at which IDCs occurred when patients were instructed to neither try to void nor to inhibit micturition during bladder filling; however, statistical significance was not established (189 +/- 122 versus 240 +/- 149 mL, respectively; P = 0.13). All other urodynamic characteristics of IDCs were similar in both methods. In conclusion, better detection rates of IDCs were achieved by instructing the patient to neither try to void nor try to inhibit micturition, but simply report his or her sensations to the examiner, during filling cystometry. If the patient is instructed to inhibit micturition during bladder filling-about 26 % of the IDC cases are misdiagnosed.}, } @article {pmid11157850, year = {2001}, author = {Sato, K and Kawasaki, H and Nagayama, H and Enomoto, M and Morimoto, C and Tadokoro, K and Juji, T and Takahashi, TA}, title = {Signaling events following chemokine receptor ligation in human dendritic cells at different developmental stages.}, journal = {International immunology}, volume = {13}, number = {2}, pages = {167-179}, doi = {10.1093/intimm/13.2.167}, pmid = {11157850}, issn = {0953-8178}, mesh = {Cell Differentiation/drug effects/immunology ; Cells, Cultured ; Chemokine CCL19 ; Chemokine CCL5/physiology ; Chemokines, CC/metabolism/physiology ; Chemotaxis, Leukocyte/drug effects ; Dendritic Cells/cytology/drug effects/*immunology/*metabolism ; Enzyme Activation/drug effects/immunology ; Focal Adhesion Kinase 1 ; Focal Adhesion Kinase 2 ; Focal Adhesion Protein-Tyrosine Kinases ; Genistein/pharmacology ; Humans ; Iodine Radioisotopes/metabolism ; JNK Mitogen-Activated Protein Kinases ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinases/immunology/metabolism ; Monocytes/immunology/metabolism ; Phosphorylation/drug effects ; Protein Binding/immunology ; Protein-Tyrosine Kinases/metabolism ; Receptors, Chemokine/biosynthesis/*immunology/*metabolism ; Signal Transduction/drug effects/*immunology ; Virulence Factors, Bordetella/pharmacology ; }, abstract = {Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, these expressions were decreased during development of iDC into mature DC (mDC) to levels similar to those of monocytes. Transcriptional expression of CCR-1, -3 and -5 was increased during differentiation of iDC from monocytes, while the expression was decreased during development of iDC into mDC. Expression of CCR-7 transcript was detected in mDC, but not in monocytes or iDC. Both monocytes and iDC, but not mDC, migrated in response to inflammatory CC chemokines such as regulated on activation normal T cell expressed and secreted (RANTES)/CCL5, whereas mDC, but not monocytes or iDC, migrated to macrophage inflammatory protein (MIP)-3ss/CCL19. Receptor engagement of monocytes or iDC by RANTES (for CCR-1, -3 and -5) resulted in protein tyrosine phosphorylation events including activation of focal adhesion kinase as well as mitogen-activated protein kinase, whereas this stimulation induced little activation of these molecular events in mDC when compared with monocytes or iDC. On the other hand, stimulation with MIP-3ss (for CCR-7) induced tyrosine phosphorylation events in mDC, but not in monocytes or iDC. These results suggest that the down-regulation of cell-surface expression of CCR and of their downstream signaling events may be involved in the reduced chemotaxis of DC to inflammatory CC chemokines during their maturation.}, } @article {pmid11149590, year = {2000}, author = {Danikas, D and Matthews, WE and Averbach, DJ}, title = {Mammary endocrine ductal carcinoma in situ: a case report.}, journal = {The American surgeon}, volume = {66}, number = {12}, pages = {1163-1164}, pmid = {11149590}, issn = {0003-1348}, mesh = {Age Distribution ; Aged ; Biopsy ; Breast Neoplasms/epidemiology/*pathology/surgery ; Carcinoma, Intraductal, Noninfiltrating/epidemiology/*pathology/surgery ; Cell Transformation, Neoplastic/*pathology ; Endocrine Gland Neoplasms/epidemiology/*pathology/surgery ; Female ; Humans ; Immunohistochemistry ; Neoplasm Invasiveness ; }, abstract = {Endocrine differentiation represents a pathway of neoplastic development available to a range of breast cancers. This pattern occurs in tumors with different morphological appearances as ductal carcinoma in situ (DCIS), mucinous carcinoma, a variant of lobular carcinoma, and low-grade invasive ductal carcinoma. Endocrine ductal carcinoma in situ is an uncommon entity. It occurs in older women with a mean age of 70 years. Histologically it shows expansile intraductal growth forming solid sheets and festoons transversed by delicate fibrovascular septa. Conventional microscopy permits the diagnosis in most cases. Specialized techniques such as immunohistochemistry and electron microscopy can serve as the basis of diagnosis in the absence of the appropriate morphological features. We present a 68-year-old female with a 1.5-cm firm mobile nodule of the left breast. Mammography and ultrasounds showed a 15 x 15-mm circumscribed solid lobulated nodule. The mass was excised and pathology was positive for endocrine DCIS. Although endocrine DCIS has a biologic marker profile similar to that of well-differentiated or noncomedo DCIS it may constitute a different histogenetic pathway of carcinogenesis in the breast. The tumor may exhibit the invasive characteristics of a neuroendocrine neoplasm. Larger studies and longer follow-up are needed for the determination of the clinical behavior.}, } @article {pmid11148574, year = {2001}, author = {Cangiarella, J and Waisman, J and Symmans, WF and Gross, J and Cohen, JM and Wu, H and Axelrod, D}, title = {Mammotome core biopsy for mammary microcalcification: analysis of 160 biopsies from 142 women with surgical and radiologic followup.}, journal = {Cancer}, volume = {91}, number = {1}, pages = {173-177}, doi = {10.1002/1097-0142(20010101)91:1<173::aid-cncr22>3.0.co;2-9}, pmid = {11148574}, issn = {0008-543X}, mesh = {Adenocarcinoma/*diagnosis/pathology ; Adult ; Aged ; Biopsy, Needle/*methods ; Breast Neoplasms/*diagnosis/pathology ; Calcinosis/*diagnosis/pathology ; Carcinoma, Ductal, Breast/*diagnosis/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Stereotaxic Techniques ; }, abstract = {BACKGROUND: Although stereotaxic fine-needle aspiration biopsy or core biopsy (14-gauge) have proven to be accurate techniques for the evaluation of mammographically detected microcalcification, the development of the Mammotome Biopsy System (Biopsys Medical, Inc., Irvine, CA) has led many medical centers to use this vacuum-assisted device for the sampling of microcalcification.

METHODS: One hundred forty-two women underwent 160 stereotaxic Mammotome core biopsies of mammographic calcification over a 1-year period. The stereotaxic procedure was performed by radiologists using the Mammotome Biopsy System. Microcalcification was evident on specimen radiographs and microscopic slides in 99% of the cases. Excisional biopsy was recommended for diagnoses of atypia or carcinoma. Patients with benign diagnoses underwent mammographic followup.

RESULTS: One hundred thirty-two benign, 12 atypical, and 15 adenocarcinoma diagnoses (comprising 1 lobular adenocarcinoma in situ [LCIS], 1 invasive ductal adenocarcinoma [IDC], and 13 intraductal adenocarcinomas [DCIS]: 10 comedo, 1 cribriform, 2 mixed cribriform and micropapillary) were rendered. Surgical excision in eight patients with atypia on Mammotome biopsy (two refused surgery, two were lost to followup) showed ductal hyperplasia in three, atypical ductal hyperplasia (ADH) in three and DCIS (low grade, solid) in two patients. Surgical excisions in 14 patients diagnosed with carcinoma (1 patient lost to followup) showed ADH in 3, ADH and LCIS in 1, residual DCIS in 8, IDC in 1, and microinvasive carcinoma in 1 patient.

CONCLUSIONS: A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was low for microcalcification diagnosed as DCIS on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling and diagnosis of mammary microcalcification.}, } @article {pmid11140941, year = {2000}, author = {Arimura, T and Nakamura, T and Hiroi, S and Satoh, M and Takahashi, M and Ohbuchi, N and Ueda, K and Nouchi, T and Yamaguchi, N and Akai, J and Matsumori, A and Sasayama, S and Kimura, A}, title = {Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy.}, journal = {Human genetics}, volume = {107}, number = {5}, pages = {440-451}, doi = {10.1007/s004390000389}, pmid = {11140941}, issn = {0340-6717}, mesh = {Adolescent ; Adult ; Aged ; Amino Acid Sequence ; Amino Acid Substitution ; Asian People/genetics ; Base Sequence ; Cardiomyopathy, Dilated/*genetics ; Carrier Proteins ; Cytoskeletal Proteins ; DNA Primers ; Exons ; Female ; Gene Frequency ; Gene Library ; *Genetic Variation ; Humans ; Japan ; LIM Domain Proteins ; Male ; Microfilament Proteins/genetics ; Middle Aged ; Molecular Sequence Data ; Muscle Proteins/*genetics ; Muscle, Skeletal/metabolism ; Mutation, Missense ; Myocardium/metabolism ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; RNA, Messenger/genetics ; Reference Values ; }, abstract = {Idiopathic dilated cardiomyopathy (IDC) is characterized by a thin-walled heart with systolic dysfunction of unknown etiology. Because abnormalities in genes for cytoskeletal proteins related to Z-disc function have recently been reported to cause IDC, genomic organization of the gene for nebulette, a novel actin-binding Z-disc protein, was determined and its sequence variations were searched for in Japanese patients with IDC and healthy controls. The nebulette gene consists of 28 exons, and four sequence variations leading to amino acid replacement (Gln187His, Met351Val, Asn654Lys, and Thr728Ala) were identified in the patients. These variations were also found in the healthy controls and hence they were polymorphisms and not disease-specific mutations. Frequencies of Gln187His, Met351Val, and Thr728Ala variants were similar in the patients and controls. However, the frequency of homozygotes for Lys at codon 654, a variant at a relatively conserved residue in an actinbinding motif, was significantly increased in nonfamilial IDC patients (n=106) as compared with healthy control subjects (n=331) (7.54% vs 1.21%, OR=6.25, P=0.002, 95% CI=1.92-20.29), while this association was not found in familial IDC patients (n=24). These observations suggest that the nebulette polymorphism in the actin-binding motif was a novel genetic marker of susceptibility to nonfamilial IDC.}, } @article {pmid11139967, year = {2000}, author = {Grimm, W and Hoffmann, J and Menz, V and Maisch, B}, title = {Relation between microvolt level T wave alternans and other potential noninvasive predictors of arrhythmic risk in the Marburg Cardiomyopathy Study.}, journal = {Pacing and clinical electrophysiology : PACE}, volume = {23}, number = {11 Pt 2}, pages = {1960-1964}, doi = {10.1111/j.1540-8159.2000.tb07062.x}, pmid = {11139967}, issn = {0147-8389}, mesh = {Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/complications/*diagnosis/physiopathology ; Baroreflex ; Bundle-Branch Block/complications/diagnosis ; Cardiac Volume ; Cardiomyopathy, Dilated/complications/*diagnosis/physiopathology ; *Electrocardiography ; Exercise Test ; Female ; Germany ; Heart Rate ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Assessment ; Severity of Illness Index ; Stroke Volume ; Ventricular Function, Left ; }, abstract = {The relation between microvolt level T wave alternans (TWA) and other noninvasive arrhythmia risk predictors was analyzed in 221 consecutive patients with idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg Cardiomyopathy Study between March 1996 and May 2000. TWA analysis was also performed in 110 healthy controls of similar age and sex. TWA during symptom-limited exercise was positive, negative and indeterminate in, respectively, 108 (49%), 65 (29%) and 48 (22%) patients with IDC versus, respectively, 5 (5%), 98 (89%) and 7 (6%) healthy controls (P < 0.05). Patients with IDC and positive TWA had a lower left ventricular (LV) ejection fraction (29 +/- 9% vs 34 +/- 10%, P < 0.05) and greater LV end-diastolic diameter (69 +/- 8 mm versus 64 +/- 6 mm, P < 0.05) than patients with negative TWA. Other variables, including age, gender, New York Heart Association functional class, presence of bundle branch block, arrhythmias on 24-hour ambulatory electrocardiogram, heart rate variability and baroreflex sensitivity, were not significantly different between patients with positive vs negative TWA. The prognostic significance of TWA in IDC with regard to arrhythmic events and total mortality will be determined by multivariate Cox analysis at the end of a 5-year follow-up in this ongoing study.}, } @article {pmid11132047, year = {2000}, author = {O'Neill, DH}, title = {Ergonomics in industrially developing countries: does its application differ from that in industrially advanced countries?.}, journal = {Applied ergonomics}, volume = {31}, number = {6}, pages = {631-640}, doi = {10.1016/s0003-6870(00)00033-8}, pmid = {11132047}, issn = {0003-6870}, mesh = {Agriculture ; *Developed Countries ; *Developing Countries ; Energy Metabolism ; *Ergonomics ; Humans ; Industry ; Mining ; Technology Transfer ; }, abstract = {Demographic characteristics of industrially developing countries (IDCs) and some comparisons with industrially advanced countries (IACs), particularly those aspects relevant to ergonomics, are presented. The majority of IDC populations are engaged in subsistence agriculture (the "informal" sector) and consideration is given to the scope for ergonomics interventions, aimed primarily at raising productivity to alleviate the poverty suffered by rural families. Ergonomics issues prevalent in the "formal" sector are also discussed and the importance of finding simple, low-cost solutions through participatory approaches emphasised. The possible contributions of ergonomics to alleviating problems common to both sectors, such as transport, are also indicated and attention is drawn to the difficulties of applying formal standards. The improvement of living and working conditions from incorporating an ergonomics approach into the sustainable livelihoods model, by enhancing human capital, is described in the context of the other livelihood assets. This demonstrates the importance of the cultural dimension for the successful delivery of ergonomics benefits. The application of ergonomics differs between IDCs and IACs particularly through the limited infrastructure in IDCs to support ergonomics activity and interventions. This broaches the different contributions that can be made by ergonomics and occupational health practitioners and implies the need for closer collaboration between these professions.}, } @article {pmid11128141, year = {2000}, author = {Kawatsu, K and Hamano, Y and Noguchi, T}, title = {Determination of domoic acid in Japanese mussels by enzyme immunoassay.}, journal = {Journal of AOAC International}, volume = {83}, number = {6}, pages = {1384-1386}, pmid = {11128141}, issn = {1060-3271}, mesh = {Animals ; Antibodies, Monoclonal ; Bivalvia/*chemistry ; Chromatography, High Pressure Liquid ; Immunoenzyme Techniques ; Indicators and Reagents ; Japan ; Kainic Acid/*analogs & derivatives/*analysis ; Marine Toxins/*analysis ; }, abstract = {Ten samples of commercial blue mussels (Mytilus edulis) from Japan were analyzed for domoic acid by an indirect competitive enzyme immunoassay (idc-EIA) based on an anti-domoic acid monoclonal antibody. Domoic acid was found in all samples at low concentrations (0.11-1.81 ng/g mussel tissue). The presence of domoic acid was confirmed by liquid chromatography coupled with immunoaffinity chromatography using an anti-domoic acid monoclonal antibody as ligand. To our knowledge, this is the first reported detection of domoic acid, a causative agent of amnesic shellfish poisoning, in Japanese mussels.}, } @article {pmid11127032, year = {2000}, author = {Le Bouëdec, G and Feillel, V and de Latour, M and Pomel, C and Dauplat, J}, title = {[Breast cancer detected by a stellar opacity. Histologic characteristics: 155 cases].}, journal = {Gynecologie, obstetrique & fertilite}, volume = {28}, number = {11}, pages = {798-805}, doi = {10.1016/s1297-9589(00)00013-8}, pmid = {11127032}, issn = {1297-9589}, mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*diagnostic imaging/pathology/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology/surgery ; Carcinoma, Lobular/diagnostic imaging/pathology/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mammography ; Middle Aged ; Receptors, Estrogen/analysis ; Retrospective Studies ; }, abstract = {UNLABELLED: Retrospective study (1985-1998) concerning surgical and histopathological features of 155 subclinical breast cancers revealed by spiculated opacity on screening mammograms.

MATERIALS AND METHODS: The patients were 44-78 years old (mean age, 58.5 years), 129 were postmenopausal. Preoperative localization was stereotactic in 57 instances (36.5%), sonographic in 98 instances (63.5%). Maximum tumor diameter varied from four to 25 millimeters (mean diameter 11 mm), below 10 min in 97 cases, below 5 mm in 15 cases. Axillary lymph node dissection was performed immediately (95%) or secondarily (5%).

RESULTS: Subclinical breast tumors exhibiting spiculated picture were infiltrating carcinomas: Infiltrating ductal carcinoma (IDC) in 130 cases (84%), infiltrating lobular carcinoma (ILC) in 25 cases (16%). Not any ductal carcinoma in situ (DCIS) was detected by such an irregular opacity. The grading according to Scarff-Bloom-Richardson was used in IDC: 95 grade I (73%), 31 grade II (24%), four grade III (3%). Hormone receptor status was obtained upon 145 tumors: both estrogen receptors were present in 125 cases (86%). Axillary lymph node involvement (N+) was found in ten cases (6%), always concerning IDC > 5 mm. Conservative surgery was achieved in mort cases (97%).

DISCUSSION: Subclinical breast cancers revealed by spiculated opacity were predominantly corresponding to infiltrating process IDC or ILC, in contrast with breast cancers revealed by microcalcifications, mainly meaning DCIS. In our experience mammographically-detected spiculated malignant tumors were not bearing unfavourable pathological or biological features: they appeared commonly well differentiated and hormonosensitive, furthermore axillary lymph nodes were rarely involved.}, } @article {pmid11123299, year = {2001}, author = {Visintin, A and Mazzoni, A and Spitzer, JH and Wyllie, DH and Dower, SK and Segal, DM}, title = {Regulation of Toll-like receptors in human monocytes and dendritic cells.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {166}, number = {1}, pages = {249-255}, doi = {10.4049/jimmunol.166.1.249}, pmid = {11123299}, issn = {0022-1767}, mesh = {Antigens, Surface/biosynthesis ; Blotting, Northern ; Cell Differentiation/immunology ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/cytology/enzymology/*metabolism ; *Drosophila Proteins ; Enzyme Activation/immunology ; Humans ; Interleukin-1 Receptor-Associated Kinases ; Lipopolysaccharides/pharmacology ; Lymphocyte Antigen 96 ; Membrane Glycoproteins/*biosynthesis/genetics/immunology ; Monocytes/cytology/enzymology/*metabolism ; Protein Kinases/metabolism ; RNA, Messenger/biosynthesis ; Receptors, Cell Surface/*biosynthesis/genetics/immunology ; Receptors, Interleukin-1/metabolism ; Toll-Like Receptor 3 ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {A number of pathogens induce immature dendritic cells (iDC) to migrate to lymphoid organs where, as mature DC (mDC), they serve as efficient APC. We hypothesized that pathogen recognition by iDC is mediated by Toll-like receptors (TLRs), and asked which TLRs are expressed during the progression of monocytes to mDC. We first measured mRNA levels for TLRs 1-5 and MD2 (a protein required for TLR4 function) by Northern analysis. For most TLRs, message expression decreased severalfold as monocytes differentiated into iDC, but opposing this trend, TLR3 and MD2 showed marked increases during iDC formation. When iDC were induced to mature with LPS or TNF-alpha, expression of most TLRs transiently increased and then nearly disappeared. Stimulation of iDC, but not mDC, with LPS resulted in the activation of IL-1 receptor-associated kinase, an early component in the TLR signaling pathway, strongly suggesting that LPS signals through a TLR. Surface expression of TLRs 1 and 4, as measured by mAb binding, was very low, corresponding to a few thousand molecules per cell in monocytes, and a few hundred or less in iDC. We conclude that TLRs are expressed in iDC and are involved in responses to at least one pathogen-derived substance, LPS. If TLR4 is solely responsible for LPS signaling in humans, as it is in mice, then its extremely low surface expression implies that it is a very efficient signal transducer in iDC.}, } @article {pmid11122455, year = {2000}, author = {Ciavarra, RP and Greene, AR and Horeth, DR and Buhrer, K and van Rooijen, N and Tedeschi, B}, title = {Antigen processing of vesicular stomatitis virus in situ. Interdigitating dendritic cells present viral antigens independent of marginal dendritic cells but fail to prime CD4(+) and CD8(+) T cells.}, journal = {Immunology}, volume = {101}, number = {4}, pages = {512-520}, pmid = {11122455}, issn = {0019-2805}, mesh = {Animals ; Antigen Presentation/*immunology ; Antigens, Viral/*immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/*immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Rhabdoviridae Infections/immunology ; Spleen/immunology ; T-Lymphocyte Subsets/*immunology ; Tumor Cells, Cultured ; Vesicular stomatitis Indiana virus/*immunology ; }, abstract = {Acute macrophage (M phi) depletion, using a liposome-mediated 'suicide technique', markedly suppressed priming of splenic CD4(+) and CD8(+) T-cell responses to vesicular stomatitis virus (VSV). However, phagocytic marginal dendritic cells (MDC), but not interdigitating dendritic cells (IDC), are now known to be also depleted by this technique. To clarify the role splenic dendritic cell (DC) subsets and M phi play in priming for a virus-specific T-cell-mediated immune response, DC and M phi were purified from VSV-infected mice and assayed for the presence of epitopes recognized by VSV helper T (Th) cells and cytotoxic T lymphocytes (CTL). Antigen pulse experiments performed in situ demonstrated that VSV Th cell and CTL epitopes became transiently associated only with DC, but not M phi or B cells, indicating that DC represent the critical antigen-presenting cell (APC) population in vivo for this virus. The failure of MDC/M phi-deficient mice to become primed was not due to the complete elimination of antigen-presenting DC because VSV peptide/class I and II complexes were detected on IDC following lipsome-mediated elimination of phagocytic cells. However, the VSV-induced chemokine response was dramatically suppressed in these mice. Thus, despite the expression of VSV peptide/class I and II complexes, IDC are not sufficient to prime VSV Th cells in the absence of MDC and/or splenic M phi.}, } @article {pmid11114860, year = {2000}, author = {Komoike, Y and Motomura, K and Inaji, H and Koyama, H}, title = {Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in situ hybridization (FISH) analysis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {4}, pages = {332-336}, doi = {10.1007/BF02966400}, pmid = {11114860}, issn = {1340-6868}, mesh = {Breast Neoplasms/*diagnosis/genetics/pathology ; Carcinoma in Situ/*diagnosis/genetics/pathology ; Carcinoma, Ductal, Breast/*diagnosis/genetics/pathology ; Female ; Humans ; *In Situ Hybridization, Fluorescence ; Monosomy ; Papilloma/*diagnosis/genetics/pathology ; }, abstract = {BACKGROUND: It is often difficult to pre-operatively diagnose ductal carcinoma in situ (DCIS)or intraductal papilloma (IDP). Current reports show that breast cancer frequently has numerical aberrations of chromosomes 1, 11 and 17. We investigated whether fluorescence in situ hybridization (FISH) analysis using three centromere-specific probes for chromosomes 1, 11 and 17 was feasible for diagnosing intraductal breast lesions.

METHODS: Fine-needle aspiration specimens from 102 breast lesions including DCIS (10), invasive ductal carcinoma (IDC) (78), IDP (7), fibroadenoma (6) and mastopathy (1) were examined for numerical aberrations on chromosomes 1, 11, 17 using FISH. If over 15% of all cells showed one signal, the sample was judged monosomic. If over 20% of cells showed three or more signals, it was considered polysomic. If the specimen had an aberration of at least one chromosome, it was judged positive.

RESULTS: Nine of 10 DCISs showed numerical aberrations of at least one chromosome whereas 65 of 78 IDCs and 2 of 14 benign lesions (containing 7 IDPs of which one case was positive) showed numerical aberrations on these chromosomes. The proportion of positive results was highest with DCIS. Moreover 6 out of 7 DCISs showed an aberration of all three chromosomes simultaneously and one case showed an aberration of two chromosomes. All aberrations in case of DCIS were polysomic while two benign lesions and 15 IDCs showed a monosomic pattern.

CONCLUSION: FISH may enable more accurate diagnosis of intraductal breast lesions.}, } @article {pmid11113011, year = {2000}, author = {Sharov, VG and Todor, AV and Silverman, N and Goldstein, S and Sabbah, HN}, title = {Abnormal mitochondrial respiration in failed human myocardium.}, journal = {Journal of molecular and cellular cardiology}, volume = {32}, number = {12}, pages = {2361-2367}, doi = {10.1006/jmcc.2000.1266}, pmid = {11113011}, issn = {0022-2828}, support = {HL-49090-06/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Atractyloside/pharmacology ; Endocardium/metabolism ; Enzyme Inhibitors/pharmacology ; Female ; Glutamic Acid/metabolism ; Heart Failure/metabolism/*physiopathology ; Heart Ventricles ; Humans ; Malates/metabolism ; Male ; Middle Aged ; Mitochondria/*metabolism/*physiology ; Myocardium/metabolism ; *Oxygen Consumption ; Phosphorylation ; }, abstract = {Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance.}, } @article {pmid11102891, year = {2000}, author = {Umekita, Y and Ohi, Y and Sagara, Y and Yoshida, H}, title = {Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients.}, journal = {International journal of cancer}, volume = {89}, number = {6}, pages = {484-487}, doi = {10.1002/1097-0215(20001120)89:6<484::aid-ijc3>3.0.co;2-s}, pmid = {11102891}, issn = {0020-7136}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/surgery ; Carcinoma, Ductal, Breast/*metabolism/surgery ; Disease-Free Survival ; ErbB Receptors/*biosynthesis ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Proportional Hazards Models ; Receptor, ErbB-2/biosynthesis ; Survival Analysis ; Transforming Growth Factor alpha/*biosynthesis ; Tumor Suppressor Protein p53/biosynthesis ; }, abstract = {Epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor-alpha (TGF-alpha), play an important role through the autocrine growth-regulation system in several human cancers, including breast cancer. However, the clinical significance of co-expression of EGF-R and TGF-alpha has not been elucidated. One hundred seventy-three female patients diagnosed as invasive ductal carcinoma who had undergone a mastectomy (159 patients) or breast-conserving surgery (14 patients) were followed up for 81 to 119 months (median 94 months) post-operatively. Immunoreactivity for EGF-R, TGF-alpha, p53 and c-erbB-2 with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Positive rates of carcinoma cells were 27%, 33%, 32% and 26% for EGF-R, TGF-alpha, p53 and c-erbB-2, respectively. Expression of EGF-R only was observed in 16% (28/173), of TGF-alpha only in 22% (38/173), of both EGF-R and TGF-alpha in 11% (19/173) and of neither in 51% (88/173). By univariate analysis, significant differences in overall survival and disease-free survival were noted according to the co-expression of EGF-R and TGF-alpha (p< 0.0001, p<0.0001), co-expression of EGF-R and c-erbB-2 (p = 0.0029, p = 0.0028), nodal status (p = 0.0028, p = 0.0001), tumor size (p = 0.0001, p<0.0001) and c-erbB-2 expression (p = 0.0034, p = 0.018), respectively. The status of p53 expression (p = 0.01), estrogen receptor (p = 0.042) and progesterone receptor (p = 0.046) showed significant differences in overall survival. According to Cox's multivariate analysis, co-expression of EGF-R and TGF-alpha had the most significant effect on disease-free survival (p<0.0001) and overall survival (p<0.0001), followed by nodal status. Co-expression of EGF-R and TGF-alpha by immunohistochemical detection is an independent prognostic indicator, and it may be helpful for determining the group of breast-cancer patients with an aggressive phenotype.}, } @article {pmid11096350, year = {2000}, author = {Sasano, H and Suzuki, T and Takeyama, J and Utsunomiya, H and Ito, K and Ariga, N and Moriya, T}, title = {17-beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma. A new development in intracrinology.}, journal = {Oncology}, volume = {59 Suppl 1}, number = {}, pages = {5-12}, doi = {10.1159/000055281}, pmid = {11096350}, issn = {0030-2414}, mesh = {Blotting, Northern ; Breast Neoplasms/*drug therapy/pathology ; Endometrial Neoplasms/*drug therapy/pathology ; Estradiol Dehydrogenases/*therapeutic use ; Female ; Humans ; Immunohistochemistry ; }, abstract = {Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of various sex steroid-dependent neoplasms including breast and endometrial carcinoma. 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) isozymes catalyze the interconversion of estradiol (E(2)) and estrone (E(1)), and thereby serve to modulate the tissue levels of bioactive E(2). 17 beta-HSD type 1 primarily catalyzes the reduction of E(1) to E(2), whereas 17 beta-HSD type 2 primarily catalyzes the oxidation of E(2) to E(1). In the human breast and its disorders, 17 beta-HSD type 1 is expressed in proliferative diseases without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17 beta-HSD type 2 is not detected in any of the lesions. In addition, 17 beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E(1), produced as a result of in situ aromatization, to E(2), a biologically potent estrogen, and exerts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17 beta-HSD type 2 is expressed, but not 17 beta-HSD type 1. 17 beta-HSD type 2 is expressed in the secretory phase but not in any proliferative phase in the endometrial mucosa. The enzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation has been detected between 17 beta-HSD type 2 immunoreactivity and age (p < 0.02). These results indicate that oxidation of E(2) to E(1) is dominant in endometrial carcinoma, 17 beta-HSD types 1 and 2 play an important role in the regulation of in situ estrogen production in breast and endometrial carcinoma.}, } @article {pmid11091721, year = {1999}, author = {Murayama, Y and Yamamoto, Y and Shimojima, N and Takahara, T and Kikuchi, K and Iida, S and Kondo, Y}, title = {T1 Breast Cancer Associated with Von Recklinghausen's Neurofibromatosis.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {6}, number = {3}, pages = {227-230}, pmid = {11091721}, issn = {1880-4233}, abstract = {A rare case of breast cancer associated with von Recklinghausen s neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis. A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skinretraction in October, 1998. The patient had von Recklinghausen fs disease (neurofibromatosis type 1). The TNM clinical staging was T1cN0M0. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pT1cN1aM0. Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.}, } @article {pmid11091720, year = {1999}, author = {Izuishi, K and Imoto, S and Hasebe, T}, title = {Signet Ring Cell Carcinoma Associated with Invasive Ductal Carcinoma of the Breast: A Case Report.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {6}, number = {3}, pages = {223-226}, doi = {10.1007/BF02967172}, pmid = {11091720}, issn = {1880-4233}, abstract = {A signet ring cell carcinoma (SRCC) associated with invasive ductal carcinoma(IDC) of the breast occurred in a 52-year-old woman. She was admitted in December 1994 for investigation of a palpable right breast mass. On physical examination a tumor measuring 2.5 x 2.1 cm was palpable in the right upper lateral portion of the breast. Ultrasonography of the breast visualized an irregular-shaped tumor. On January 1995, modified radical mastectomy was performed, and the postoperative course was uneventful. Histological examination revealed a tumor consisting of IDC with a component of SRCC that occupied about 40 % of the area of the invasive carcinoma. We reviewed the cases of IDC with SRCC from the Japanese literature with consideration of the characteristics and problems of this rare tumor.}, } @article {pmid11091703, year = {1999}, author = {Saimura, M and Fukutomi, T and Tsuda, H and Tanaka, SA and Nanasawa, T}, title = {Breast Carcinoma with Osteoclast-like Giant Cells: A Case Report and Review of the Japanese Literature.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {6}, number = {2}, pages = {121-126}, doi = {10.1007/BF02966918}, pmid = {11091703}, issn = {1880-4233}, abstract = {A 41-year-old premenopausal woman with a 3.5 cm freely mobile mass in the upper outer quadrant of the right breast was admitted to our hospital. Fine needle aspiration showed malignant epithelial cells and many multinucleated osteoclast-like giant cells (OGCs). Excisional biopsy revealed an invasive ductal carcinoma. A right modified radical mastectomy was subsequently performed. Macroscopically the tumor was well circumscribed with a dark brown cut surface. Microscopically, the tumor was a grade 2 invasive ductal carcinoma with many multinucleated OGCs adjacent the tumor cells and hemorrhage and infiltration of inflammatory cells in the stroma. The intra-mammary metastasis also contained OGCs and stromal reactions. By enzyme immunoassay, the tumor cells were negative for estrogen receptor but positive for progesterone receptor. The tumor cells were negative for both c-erbB-2 and p53. The OGCs showed positive immunostaining with the monoclonalantibody CD68, demonstrating a histiocytic origin. Lymph nodes were free of metastasis. We also review the Japanese literature concerning breast carcinoma withOGCs.}, } @article {pmid11091649, year = {1998}, author = {Okano, K and Fukutomi, T and Tsuda, H and Tanaka, SA and Nanasawa, T and Kanai, Y}, title = {Local Recurrence after Conservative Surgery without Postoperative Radiation for Pure Tubular Carcinoma of the Breast:A Case Report with Reference to Multifocality of Tubular Carcinoma.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {5}, number = {2}, pages = {201-204}, doi = {10.1007/BF02966696}, pmid = {11091649}, issn = {1880-4233}, abstract = {A 49-year-old premenopausal woman with stage I breast carcinoma underwent left quadrantectomy with axillary dissection in 1992. The tumor was 0.7x0.5 cm Histopathologically, this was a pure tubular carcinoma without lymph node metastasis or lymphatic or vascular invasion. Although the surgical margin was pathologically negative, atypical ductal hyperplasia was present close to the cut margin's edge. Neither adjuvant chemotherapy nor radiotherapy had been given after the operation. Approximately 5 years after the first surgery, she had a local recurrence in the vicinity of the operative wound. There was no clinical evidence of distant metastasis. A salvage mastectomy was performed. Histopathological examination revealed that the second tumor was an invasive ductal carcinoma, histological grade 2, with extensive intraductal component. It was difficult to determine whether this was a true in-breast recurrence or a second primary cancer. Overexpression of p53 and c-erbB-2 was observed in the second tumor. Estrogen receptor and progesterone receptor were both negative. No postoperative chemotherapy was given. Multifocality and atypical ductal hyperplasia were observed in 7(87.5%)and 6(75%) of 8 patients, respectively, with tubular carcinoma between 1991and 1997 at the National Cancer Center Hospital. Coexisting disease associated with tubular carcinoma suggests that radiotherapy may be an important component of breast conservation treatment to prevent local recurrence in this type of tumor.}, } @article {pmid11091648, year = {1998}, author = {Adachi, Y and Kakisako, K and Sato, K and Shiraishi, N and Kitano, S}, title = {Paget's Disease of the Breast: Report of Five Cases and Review of the Japanese Literature.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {5}, number = {2}, pages = {195-200}, doi = {10.1007/BF02966695}, pmid = {11091648}, issn = {1880-4233}, abstract = {Five cases of Paget's disease of the breast are presented, and 76 cases reported in the Japanese literature are analyzed. Paget's disease of the breast is often confined to the nipple-areolar complex(68%), and the duration of symptoms issometimes more than 5 years(25%). Paget's disease without palpable tumor in theunderlying breast is characterized by a low incidence of invasive ductal carcinoma(8%), lymph node metastasis(8%), and stage II or greater disease(0%). These cases indicate that Paget's disease without palpable breast tumor has less aggressive behavior and more benign course than that with palpable breast tumor, and local excision and/or radiation therapy may be an alternative to mastectomy as the initial treatment.}, } @article {pmid11091616, year = {1997}, author = {Hiramatsu, H and Enomoto, K and Ikeda, T and Mukai, M and Furukawa, J and Kikuchi, K and Oshio, K and Hiraoka, N and Kitajima, M and Hiramatsu, K}, title = {The Role of Contrast-Enhanced High Resolution MRI in the Surgical Planning of Breast Cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {4}, number = {4}, pages = {285-290}, doi = {10.1007/BF02966523}, pmid = {11091616}, issn = {1880-4233}, abstract = {The role of contrast-enhanced high resolution MRI for planning surgery in breast cancer was evaluated. Of 72 patients examined, 57 patients had invasive ductal carcinoma, 2 had mucinous carcinoma, 1 had medullary carcinoma, 7 had invasive lobular carcinoma, 2 had ductal carcinoma in situ (DCIS) and 3 had Paget's disease. A 1.5 T Signa imager (GE Medical Systems, Milwaukee, WI) was used with a dedicated breast coil. The pulse sequence based on RARE(rapid acquisition with relaxation enhancement) was used with a fat suppression technique. After examining both breasts, the affected breast alone was examined with Gd enhancement. Linear and/or spotty enhancement on MRI was considered to suggest DCIS or intraductal spread in the area surrounding the invasive cancer. Of 72 patients, 50 showed linear and/or spotty enhancement on MRI and 41 of those 50 patients had DCIS or intraductal spread. In contrast, 22 of 72 patients were considered to have little or no intraductal spread on MRI and 17 of the 22 patients had no or little intraductal spread on pathological examination. The sensitivity, specificity and accuracy for detecting intraductal spread on MRI were 89%, 82% and 81%, respectively. Discrepancies in the estimated extent of intraductal spread were less than 2 cm in 90% of the patients according to pathological mapping. High resolution MRI was considered useful in detecting intraductal spread and in estimating its extent, however, larger study using precise correlation with pathology is necessary.}, } @article {pmid11088049, year = {2000}, author = {Song, MM and Nio, Y and Dong, M and Tamura, K and Furuse, K and Tian, YL and He, SG and Shen, K}, title = {Comparison of K-ras point mutations at codon 12 and p21 expression in pancreatic cancer between Japanese and Chinese patients.}, journal = {Journal of surgical oncology}, volume = {75}, number = {3}, pages = {176-185}, doi = {10.1002/1096-9098(200011)75:3<176::aid-jso5>3.0.co;2-w}, pmid = {11088049}, issn = {0022-4790}, mesh = {Aged ; China ; Female ; Genes, ras/*genetics ; Humans ; Japan ; Male ; Middle Aged ; Pancreatic Neoplasms/ethnology/*genetics/pathology ; *Point Mutation ; Proto-Oncogene Proteins p21(ras)/*genetics ; Survival Analysis ; }, abstract = {BACKGROUND AND OBJECTIVES: K-ras (Kirsten-ras) point mutation (PM) in codon 12 are suggested to be significantly associated with the tumorigenesis of pancreatic cancer. The incidences of K-ras PMs in human pancreatic cancer are reported to be different between Europeans and Japanese. The present study was designed to compare the incidences and profile of K-ras PMs and ras-p21 expression in primary invasive ductal carcinoma (IDC) of the pancreas between Japanese and Chinese.

METHODS: The specimens included 51 Japanese and 34 Chinese patients with the primary IDC of the pancreas. K-ras PMs were tested by allele specific oligonucleotide dot blot hybridization methods and ras-p21 expression was stained by the immunohistochemical method.

RESULTS: K-ras PMs were detected in 48 Japanese IDCs (94%) and in 24 Chinese ones (71%). There was a significant difference between the two groups. The GAT mutation was more frequent both in Japanese (61%, 33/54) and in Chinese (60%, 18/30) IDCs. The transitions/transversions ratio in the Japanese group was 2.4 in this study. By contrast, that in the Chinese group was 1.5. The expression of p21 was detected in 24 Japanese IDCs (47%) and in 24 Chinese IDCs (71%). There was a significant difference between the two groups. The expression of p21 and the patterns of K-ras PMs did not show any significant influence on the survival of the patients both in Japanese and Chinese. In the present study, Chinese IDC had a lower frequency of K-ras PMs in codon 12 than Japanese IDC. The pattern of K-ras PMs in Chinese IDC was different from that in Japanese and European IDC, respectively.

CONCLUSIONS: Ki-ras PM and p21 expression were frequently seen both in Japanese and Chinese patients with pancreatic cancer. Factors such as lifestyle and environment may have influences on pancreatic carcinogenesis in various populations.}, } @article {pmid11087636, year = {2000}, author = {Sinha, PS and Bendall, S and Bates, T}, title = {Does routine grading of invasive lobular cancer of the breast have the same prognostic significance as for ductal cancers?.}, journal = {European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology}, volume = {26}, number = {8}, pages = {733-737}, doi = {10.1053/ejso.2000.0994}, pmid = {11087636}, issn = {0748-7983}, mesh = {Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging/methods ; Predictive Value of Tests ; Prognosis ; Recurrence ; Reproducibility of Results ; Retrospective Studies ; Survival Analysis ; }, abstract = {AIM: The routine tumour grading of invasive ductal carcinoma of the breast has been shown to be a robust determinant of outcome but pathologists have been reluctant to grade lobular cancers. The aim of this study was to determine the prognostic significance of the routine reporting of lobular grade.

METHODS: All patients with invasive lobular carcinoma (ILC) treated between 1981 and 1996 were reviewed. Patients with ILC which had been graded were included in the study. These cases were matched with two control patients with invasive ductal carcinoma (IDC) who were operated on in the same year and were closest to the patients in age. Recurrence-free survival was compared with grade for ILC cases and IDC controls using life-table analysis. Similar comparisons were made with the Nottingham Prognostic Index (NPI) between the different prognostic groups.

RESULTS: Of 139 cases with ILC, 33 were excluded from the study because 24 were ungraded, five had advanced disease and four had mixed tumours. The mean length of follow-up for ILC cases was 75 months vs 70 months for IDC controls. Recurrence rates for grade I were 10% ILC vs 24% IDC, for grade II 32%vs 32% and for grade III 33%vs 49%. The reported grades for ILC and IDC both showed the expected trend for an increased recurrence rate with more severe tumour grade, but this was only significant for IDC grade II vs grade III (P<0.02) on life-table analysis; only 6% of lobular cancers were reported as grade III. However, there was significant separation of the survival curves when NPI was compared for both lobular and ductal cancers.

CONCLUSION: The routine reporting of tumour grade for ILC did not show significant difference in outcome between grade I and grade II, and very few tumours were rated grade III. The validity of grading lobular cancer of the breast requires further evaluation.}, } @article {pmid11078278, year = {2000}, author = {Naqvi, TZ and Goel, RK and Forrester, JS and Davidson, RM and Siegel, RJ}, title = {Usefulness of left ventricular mass in predicting recovery of left ventricular systolic function in patients with symptomatic idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {85}, number = {5}, pages = {624-629}, doi = {10.1016/s0002-9149(99)00822-x}, pmid = {11078278}, issn = {0002-9149}, mesh = {Cardiomyopathy, Dilated/*diagnosis/epidemiology ; Case-Control Studies ; Echocardiography ; Follow-Up Studies ; Humans ; Hypertrophy, Left Ventricular/*diagnosis/diagnostic imaging/epidemiology ; Middle Aged ; Prognosis ; Prospective Studies ; Stroke Volume/physiology ; Systole/physiology ; Time Factors ; *Ventricular Function, Left ; }, abstract = {Prognosis of idiopathic dilated cardiomyopathy (IDC) is variable. We determined the prognostic value of left ventricular (LV) mass and systolic and diastolic function in patients with IDC of <12 months duration. Clinical and echocardiographic assessment was performed at baseline and at 8+/-6 months follow-up in 25 patients (47+/-13 years) with IDC and an LV ejection fraction (LVEF1) of <40% (22+/-7%). Based on a follow-up LVEF (LVEF2) of < or >40%, patients were divided into unimproved (n = 13, LVEF2 = 21+/-9%) and improved groups (n = 12, LVEF2 = 51+/-11%). There was no difference in the LVEF1 (22+/-8% vs. 22+/-6%), LV end-systolic (5.7+/-0.8 vs. 5.8+/-0.9 cm) or end-diastolic (6.5+/-0.6 vs. 6.6+/-0.9 cm) dimension, wall stress (102+/-26 vs 99+/-28 g/cm2), end-systolic (1.7+/-0.3 vs. 1.8+/-0.2) or end-diastolic (1.7+/-0.3 vs. 1.6+/-0.1) sphericity, dp/dt (582+/-163 vs. 678+/-222 mm Hg/s), or right ventricular fractional shortening (20+/-9% vs. 27+/-7%, p = 0.06) in unimproved and improved groups. LV mass was lower (1.00+/-0.21 vs. 1.38+/-0.27 g/ml, p = 0007) and mitral inflow E-wave deceleration time shorter (97+/-42 vs. 164+/-58 ms, p = 0007) in the unimproved versus the improved group. On Pearson correlation analysis, LV mass (r = 0.62, p = 0.001), deceleration time (r = 0.68, p = 0.0002), wall motion score index (r = -0.47, p = 02), and dp/dt (r = 0.52, p = 03) were the significant predictors of LVEF2. There was correlation between LV mass (grams per milliliter) and deceleration time (r = 0.61, p = 0.001). During follow-up, death occurred in 1, and readmission for worsening heart failure in 4 patients in the unimproved group versus no hospitalization in the improved group. Thus, in patients with recent onset IDC, LV mass and diastolic function determine late outcome.}, } @article {pmid11078277, year = {2000}, author = {Fauchier, L and Babuty, D and Cosnay, P and Poret, P and Rouesnel, P and Fauchier, JP}, title = {Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {85}, number = {5}, pages = {618-623}, doi = {10.1016/s0002-9149(99)00821-8}, pmid = {11078277}, issn = {0002-9149}, mesh = {Arrhythmias, Cardiac/epidemiology ; Cardiomyopathy, Dilated/*diagnosis/mortality ; Death, Sudden, Cardiac/epidemiology ; Electrocardiography/*methods ; Electrocardiography, Ambulatory/methods ; Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Risk Assessment ; *Signal Processing, Computer-Assisted ; Survival Analysis ; Time Factors ; }, abstract = {The aim of this study was to evaluate the long-term prognostic value of signal-averaged electrocardiography (SAECG) in idiopathic dilated cardiomyopathy (IDC). Time domain analysis of SAECG was assessed in 131 patients with angiographically confirmed IDC (age 52+/-12 years; 108 men; left ventricular ejection fraction 33+/-12%) using specific criteria in 44 patients with bundle branch block. Late potentials (LP) on SAECG were present in 27% of the patients. Patients with LP had a similar left ventricular ejection fraction and a similar left ventricular end-diastolic diameter than patients with a normal SAECG. With a follow-up of 54+/-41 months, 24 patients suffered cardiac death and 19 had major arrhythmic events (sudden death, resuscitated ventricular fibrillation, or sustained ventricular tachycardia). Patients with LP had an increased risk of all-cause cardiac death (RR 3.3, 95% confidence interval 1.5 to 7.5, p = 0.004) and of arrhythmic events (RR 7.2, 95% confidence interval 2.6 to 19.4, p = 0.0001). Using multivariate analysis, only LP on SAECG (p = 0.001), reduced SD of all normal-to-normal intervals (SDNN) (p = 0.002), increased pulmonary capillary wedge pressure (p = 0.005), and history of sustained ventricular tachyarrhythmia (p = 0.02) predicted cardiac death. A history of previous sustained ventricular tachyarrhythmia (p = 0.0001), reduced SDNN (p = 0.003), and LP on SAECG (p = 0.006) were the only independent predictors of major arrhythmic events. Results were not altered when considering separately patients with or without bundle branch block, or after exclusion of patients with a history of sustained ventricular tachyarrhythmia. This study is one of the first to suggest that LP on SAECG is an independent predictor of all-cause cardiac death and is of high interest for arrhythmia risk stratification in IDC.}, } @article {pmid11077126, year = {2000}, author = {Agarwal, AK and Venugopalan, P and Meharali, AK and de Debono, D}, title = {Idiopathic dilated cardiomyopathy in an Omani population of the Arabian Peninsula: prevalence, clinical profile and natural history.}, journal = {International journal of cardiology}, volume = {75}, number = {2-3}, pages = {147-58; discussion 158-9}, doi = {10.1016/s0167-5273(00)00315-6}, pmid = {11077126}, issn = {0167-5273}, mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/diagnosis/*epidemiology/mortality ; Female ; Humans ; Male ; Middle Aged ; Oman/epidemiology ; Prevalence ; Prognosis ; Prospective Studies ; }, abstract = {We have analysed prospectively the prevalence and clinical profile of idiopathic dilated cardiomyopathy (IDC) in a circumscribed native population of the Sultanate of Oman over 3 years (1992-1994). Identified patients were followed up for a period ranging from 1 to 8 years (median 4 years) and the variables related to outcome determined. IDC was diagnosed in 97 patients, giving a prevalence of 43.2/100,000 population during the study period. 84.5% of patients were aged over 35 years and males outnumbered females (M/F=1.4:1). Factors related to poor outcome were an initial left ventricular ejection fraction 30%.}, } @article {pmid11062111, year = {2000}, author = {Ruibal, A and Schneider, J and del Río, MC and Arias, J and Núñez, MI and Tejerina, A}, title = {[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases].}, journal = {Revista espanola de medicina nuclear}, volume = {19}, number = {5}, pages = {350-355}, doi = {10.1016/s0212-6982(00)71889-1}, pmid = {11062111}, issn = {0212-6982}, mesh = {Adenocarcinoma, Mucinous/immunology ; Antigens, Neoplasm/*analysis ; Breast/immunology ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Carcinoma, Medullary/immunology ; Female ; Fibroadenoma/immunology ; Fibrocystic Breast Disease/immunology ; Glycoproteins/*analysis ; Humans ; Hyaluronan Receptors/*analysis ; Neoplasms, Hormone-Dependent/*immunology ; }, abstract = {In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.}, } @article {pmid11060371, year = {2000}, author = {Hama, Y and Kaji, T and Iwasaki, Y and Hinokiyama, K and Shimizu, M and Kusano, S}, title = {Successful transcatheter embolization of penetrating aortic ulcer using interlocking detachable coils.}, journal = {Cardiovascular and interventional radiology}, volume = {23}, number = {5}, pages = {391-393}, doi = {10.1007/s002700010089}, pmid = {11060371}, issn = {0174-1551}, mesh = {Aortic Dissection/diagnostic imaging/etiology/*therapy ; Aortic Aneurysm, Thoracic/diagnostic imaging/etiology/*therapy ; Arteriosclerosis/complications ; Embolization, Therapeutic/*instrumentation ; Equipment Design ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; }, abstract = {A 54-year-old man with persistent chest pain was hospitalized for hypertension and DeBakey type IIIb aortic dissection. The false lumen of the dissection was almost completely thrombosed; however, a penetrating atherosclerotic ulcer (PAU) was observed 5 weeks later. At that time, we successfully embolized the PAU with a microcatheter and interlocking detachable coils (IDCs). The patient is well with no episodes of relapse in 20 months of follow-up. This case suggests the utility of the microcatheter and IDC system as an alternative to surgery.}, } @article {pmid11060273, year = {2000}, author = {Ruibal, A and Arias, J and del Río, MC and San Román, JM and Lapeña, G and Pardo, C and Tejerina, A}, title = {[Clinico-biological impact of pS2 positivity in estrogen receptor negative-infiltrating ductal carcinomas of the breast].}, journal = {Revista espanola de medicina nuclear}, volume = {19}, number = {6}, pages = {428-433}, doi = {10.1016/s0212-6982(00)71905-7}, pmid = {11060273}, issn = {0212-6982}, mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; Carcinoma, Ductal, Breast/*chemistry ; Cytosol/chemistry ; ErbB Receptors/analysis ; Female ; Humans ; Proteins/*analysis ; *Receptors, Estrogen ; Receptors, Progesterone/analysis ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; }, abstract = {UNLABELLED: The pS2 protein is regulated by estrogens, but it can also be expressed in hormone independent breast carcincomas. We have carried out the present study in order to analyze the clinical-biological impact of pS2 positivity (>2 ng/mg prt.) in negative estrogen receptors (< 10 fmol/mg prt.) infiltrating ductal breast carcinomas (IDC).

MATERIAL AND METHODS: 97 negative ER-IDC have been included in our study. We established the doses of the cytosol levels of pS2, progesterone receptors (PR), cathepsin D, tissue -type plasminogen activator (t-PA) and hyaluronic acid (HA), as well as the levels of HA, epidermal growth factor receptor (EGFR), CD44v5 and CD44v6 in cell surface membranes. We also considered the menopausal status, histological grade, ploidy, cellular synthesis phase, tumor size, axillary lymph node involvement and the existence of distant metastasis. The same results were obtained when the progesterone receptor status was also considered.

RESULTS: ER-/pS2+ IDC presented higher (p <0,05) PR, t-PA and HA cytosol level, as well as lower EGFR concentrations, S-phase > 7% and S-phase >14% and lower N+>10 percentages and aneuploidy. They were also more frequently CD44v6+. The same results were observed when the positivity of the progesterone receptors was considered.

CONCLUSIONS: The above results lead us to consider that the positivity for pS2 in ER- IDC is associated with hormone-dependent parameters, good differentiation and lower cellular proliferation, which can explain a better clinical outcome.}, } @article {pmid11053725, year = {2000}, author = {Mizuno, Y and Yoshimura, M and Harada, E and Nakayama, M and Sakamoto, T and Shimasaki, Y and Ogawa, H and Kugiyama, K and Saito, Y and Nakao, K and Yasue, H}, title = {Plasma levels of A- and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {86}, number = {9}, pages = {1036-40, A11}, doi = {10.1016/s0002-9149(00)01147-4}, pmid = {11053725}, issn = {0002-9149}, mesh = {Aged ; Atrial Natriuretic Factor/*blood ; Biomarkers/blood ; Cardiomyopathy, Dilated/*blood/diagnosis ; Cardiomyopathy, Hypertrophic/*blood/diagnosis ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Natriuretic Peptide, Brain/*blood ; Probability ; Prognosis ; Reference Values ; Sensitivity and Specificity ; Severity of Illness Index ; Stroke Volume ; }, abstract = {We investigated the relation between left ventricular structure and the secretion patterns of A- and B-type natriuretic peptides (ANP and BNP) by comparing their plasma levels in patients with hypertrophic cardiomyopathy (HC) and patients with idiopathic dilated cardiomyopathy (IDC). The secretion of ANP and BNP was much higher in patients with HC than in those with IDC; this shows that left ventricular cavity size is a key factor that regulates the secretion of ANP and BNP.}, } @article {pmid11044038, year = {2000}, author = {Darling, ML and Smith, DN and Lester, SC and Kaelin, C and Selland, DL and Denison, CM and DiPiro, PJ and Rose, DI and Rhei, E and Meyer, JE}, title = {Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision.}, journal = {AJR. American journal of roentgenology}, volume = {175}, number = {5}, pages = {1341-1346}, doi = {10.2214/ajr.175.5.1751341}, pmid = {11044038}, issn = {0361-803X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Automation ; Biopsy, Needle/instrumentation/*methods ; Breast/*pathology/surgery ; Calcinosis/pathology/surgery ; Carcinoma in Situ/*pathology/surgery ; Carcinoma, Ductal, Breast/*pathology/surgery ; Chi-Square Distribution ; Equipment Design ; Female ; Follow-Up Studies ; Humans ; Hyperplasia ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Stereotaxic Techniques ; Ultrasonography, Interventional ; Ultrasonography, Mammary ; Vacuum ; }, abstract = {OBJECTIVE: This investigation compares the frequency of histologic underestimation of breast carcinoma that occurs when a large-core needle biopsy reveals atypical ductal hyperplasia or ductal carcinoma in situ with the automated 14-gauge needle, the 14-gauge directional vacuum-assisted biopsy device, and the 11-gauge directional vacuum-assisted biopsy device.

SUBJECTS AND METHODS: Evaluation of 428 large-core needle biopsies yielding atypical ductal hyperplasia (139 lesions) or ductal carcinoma in situ (289 lesions) was performed. The results of subsequent surgical excision were retrospectively compared with the needle biopsy results.

RESULTS: For lesions initially diagnosed as ductal carcinoma in situ, underestimation of invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device when compared with the automated 14-gauge needle (10% versus 21%, p < 0.05) but was not significantly less frequent when compared with the 14-gauge directional vacuum-assisted device (10% versus 17%, p > 0.1). For lesions diagnosed initially as atypical ductal hyperplasia, underestimation of ductal carcinoma in situ and invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device compared with the 14-gauge directional vacuum-assisted device (19% versus 39%, p = 0. 025) and with the automated 14-gauge needle (19% versus 44%, p = 0. 01).

CONCLUSION: The frequency of histologic underestimation of breast carcinoma in lesions initially diagnosed as atypical ductal hyperplasia or ductal carcinoma in situ using large-core needle biopsy is substantially lower with the 11-gauge directional vacuum-assisted device than with the automated 14-gauge needle and with the 14-gauge directional vacuum-assisted device.}, } @article {pmid11029808, year = {2000}, author = {Kanoh, T and Iino, Y and Horiguchi, J and Takei, H and Maemura, M and Yokoe, T and Morishita, Y}, title = {A case report of advanced male breast cancer with an objective response to tamoxifen treatment.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {3}, pages = {256-260}, doi = {10.1007/BF02967470}, pmid = {11029808}, issn = {1340-6868}, mesh = {Aged ; Antineoplastic Agents, Hormonal/*therapeutic use ; Biopsy ; Brain Neoplasms/*secondary ; Breast Neoplasms, Male/*drug therapy/*pathology/psychology ; Carcinoma, Ductal, Breast/*secondary ; Fatal Outcome ; Humans ; Lung Neoplasms/*secondary ; Male ; Neoplasm Staging ; Quality of Life ; Tamoxifen/*therapeutic use ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago. The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall. Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.}, } @article {pmid11029799, year = {2000}, author = {Tsuda, H and Takarabe, T and Akashi-Tanaka, S and Fukutomi, T and Nanasawa, T and Watanabe, T}, title = {Evaluation of histopathological criteria for identifying node-negative breast cancer with high risk of early recurrence in the NSAS-BC protocol study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {3}, pages = {201-209}, doi = {10.1007/BF02967461}, pmid = {11029799}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy/methods/*standards ; Breast Neoplasms/*pathology/surgery ; Clinical Protocols/standards ; Female ; Humans ; Japan ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local/*pathology/surgery ; Neoplasm Staging/methods/*standards ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: The histopathological criteria for high-risk node-negative primary breast cancer stated in the National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) protocol were used to grade a consecutive series of 488 cases at our hospital.

METHODS: To validate the criteria retrospectively, we examined the histological features of node-negative primary breast cancers which showed early relapse within 2 years after surgical therapy.

RESULTS: Early relapse occurred in 12 patients, distant metastases in 11, and local recurrence in one. Among 278 cases followed for up to 1.5 years or longer, early systemic relapse was detected in 10 (5.8%) of 172 higher-grade tumors (9 invasive ductal carcinomas of nuclear grade 3 and one invasive ductal carcinoma of nuclear grade 2) and one stromal cell sarcoma. Among the 115 low-risk tumors, only one case (0.9%) of invasive ductal carcinomas with nuclear grade 1 showed early local recurrence. Early relapse occurred in only one (1.5%) of 67 tumors with an invasive component of 1.0 cm but in 11 (5.2%) of 211 tumors with an invasive component of 1.1 cm. The recurrence rate increased to 9.3% (8/86) when tumor invasion was 2.1 cm. In 12 cancers showing recurrence, strand structure, large central acellular zones, and squamoid features were histologically observed in four, two, and three cases, respectively. The present results confirmed the reported tendency of correlation between strand pattern and bone metastasis, large central acellular zones and lung and brain metastasis, and squamoid features and lung metastasis. Synchronous bilateral and unilateral multiple cancers were characterized by lower nuclear grades.

CONCLUSIONS: At our hospital, the criteria used in the NSAS-BC protocol were demonstrated to identify node-negative cancers with high risk of early recurrence at a hospital level. To further identify groups prone to recurrence, longer follow-up would be necessary. In addition, the histological criteria could be improved to correlate with patient outcome more accurately.}, } @article {pmid11029794, year = {2000}, author = {Nagasawa, M and Iino, Y and Horiguchi, J and Takei, H and Maemura, M and Horii, Y and Matsumoto, H and Nagaoka, H and Oyama, T and Nakajima, T and Morishita, Y}, title = {Sudden hemorrhage of the breast caused by breast cancer: a case report and review of the literature.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {2}, pages = {176-178}, doi = {10.1007/BF02967454}, pmid = {11029794}, issn = {1340-6868}, mesh = {Aged ; Breast Diseases/*etiology ; Breast Neoplasms/*complications ; Carcinoma, Ductal, Breast/*complications ; Female ; Hemorrhage/*etiology ; Humans ; }, abstract = {A rare case of sudden hemorrhage caused by breast cancer is reported. A 71-year-old woman noted bleeding from her left breast. Physical examination of the left breast showed a localized open cavity accompanied by bleeding and coagulation. The patient had no history of breast trauma or anticoagulation therapy. Incisional biopsy followed by histological examination resulted in a diagnosis of granulation tissue with no cancer cells present. Mammography and ultrasonography indicated probable breast cancer. As a result, a second incisional biopsy was performed, which suggested invasive ductal carcinoma without histological skin invasion. A modified radical mastectomy was performed under a diagnosis of stage II breast cancer. Breast cancer with sudden hemorrhage is rare. We review the literature and discuss the cause of this unusual manifestation.}, } @article {pmid11029768, year = {2000}, author = {Yu, Y and Morimoto, T and Sasa, M and Okazaki, K and Harada, Y and Fujiwara, T and Irie, Y and Takahashi, E and Tanigami, A and Izumi, K}, title = {Human papillomavirus type 33 DNA in breast cancer in Chinese.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {7}, number = {1}, pages = {33-36}, doi = {10.1007/BF02967185}, pmid = {11029768}, issn = {1340-6868}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blotting, Southern ; Breast Neoplasms/epidemiology/ethnology/*virology ; Carcinoma, Ductal, Breast/epidemiology/ethnology/*virology ; China/epidemiology ; DNA Probes, HPV ; DNA, Neoplasm/genetics/*isolation & purification ; DNA, Viral/genetics/*isolation & purification ; Female ; Genes, Viral ; Humans ; Middle Aged ; Papillomaviridae/classification/genetics/*isolation & purification/pathogenicity ; Papillomavirus Infections/epidemiology/ethnology/*virology ; Polymerase Chain Reaction ; Tumor Virus Infections/epidemiology/ethnology/*virology ; }, abstract = {BACKGROUND: The association between human papillomavirus (HPV) and anogenital tumors, especially cervical cancer, is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer.

METHODS: We used PCR and Southern blot hybridization to analyze HPV-related DNA specimens from 32 cases of invasive ductal carcinoma operated upon in the Shanghai region of China.

RESULTS: DNA derived from HPV33 was detected in 14 cases (43.8%). No HPV16 or HPV18 DNA was detected in any of the cases in this study. This is the first report demonstrating a correlation between HPV33 infection and breast cancer.

CONCLUSIONS: Our results suggest that HPV33 infection may be involved in the pathogenesis of breast cancer in Chinese.}, } @article {pmid11026070, year = {2000}, author = {Hernández-Cadena, L and Téllez-Rojo, MM and Sanín-Aguirre, LH and Lacasaña-Navarro, M and Campos, A and Romieu, I}, title = {[Relationship between emergency consultations for respiratory diseases and air pollution in Juarez City, Chihuahua].}, journal = {Salud publica de Mexico}, volume = {42}, number = {4}, pages = {288-297}, pmid = {11026070}, issn = {0036-3634}, mesh = {Acute Disease ; Adolescent ; *Air Pollution ; Asthma/*epidemiology ; Child ; Child, Preschool ; Emergency Service, Hospital/*statistics & numerical data ; Humans ; Infant ; Mexico ; Respiratory Tract Infections/*epidemiology ; *Urban Health ; }, abstract = {OBJECTIVE: To assess the relationship of < or = 10 microns particles (PM10) and atmospheric ozone concentrations, with the daily number of emergency visits due to asthma and acute respiratory diseases, among children aged under 15, living in Ciudad Juarez, Chihuahua, Mexico.

MATERIAL AND METHODS: Between 1998 and 1999, an ecologic study was conducted. Atmospheric data were obtained from the Environmental Protection Agency (EPA), from eight monitoring stations located in Ciudad Juarez, Chihuahua, and EI Paso, Texas. From July 1997 to December 1998, data from emergency room visits for respiratory illness were abstracted from existing medical records of two Mexican Institute of Social Security (IMSS) hospitals in Ciudad Juarez. Diagnoses were classified into two groups: a) asthma, and b) upper respiratory infections (URI), according to the International Classification of Diseases (ICD-9 and/or IDC-10). Statistical analysis was carried out using the Poisson regression time series method.

RESULTS: During the study period, the mean 24-hour PM10 level was 34.46 micrograms/m3 (SD = 17.99) and the mean ozone level was 51.60 ppb (SD = 20.70). The model shows that an increase of 20 micrograms/m3 in the mean 24-hour exposure to PM10 was related to an increase of 4.97% (95% CI 0.97-9.13) in emergency visits for asthma, with a 5-day lag, as well as to an increase of 9% (95% CI 1.8-16.8) when a cumulative 5-day exposure was considered. URI increased 2.95% as a cause of emergency room visits, for each 20 micrograms/m3 increase in the mean 24-hour exposure to PM10. The impact of PM10 on emergency visits for asthma was greater on days with ozone ambient levels exceeded 49 ppb (median value).

CONCLUSIONS: A positive association was found between environmental PM10 and ozone concentrations and the daily number of emergency room visits due to asthma and acute respiratory diseases, even with levels lower than the Mexican standard levels. Also, a synergic effect between PM10 and O3 was found.}, } @article {pmid11021468, year = {2000}, author = {Ingelmo, C and Frame, LH}, title = {Mechanism for site-dependent differences in the shape of the resetting response curve in fixed barrier reentry.}, journal = {Journal of cardiovascular electrophysiology}, volume = {11}, number = {9}, pages = {981-989}, doi = {10.1111/j.1540-8167.2000.tb00170.x}, pmid = {11021468}, issn = {1045-3873}, support = {HL38386/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Electric Stimulation ; Heart Conduction System/physiopathology ; Tachycardia, Atrioventricular Nodal Reentry/*physiopathology ; Tachycardia, Ventricular/physiopathology ; }, abstract = {INTRODUCTION: We investigated whether the site of stimulation within a reentrant circuit affects the resetting response curve (RRC). RRCs are used to characterize the excitable gap of reentrant circuits, including the duration of the fully excitable gap and the presence of partially excitable tissue.

METHODS AND RESULTS: We reset proximal and distal to a site of interval-dependent conduction (IDC) in canine in vitro atrial tricuspid rings. Adjustable reentry allowed changes in the cycle length and direction of reentry. In nine preparations we reset 26 tachycardias. In the 16 tachycardias with one site of IDC, RRCs were significantly different when stimulating distal and proximal to a site of interval-dependent conduction. For the distal curves, the duration of the flat portion was 42 +/- 26 msec greater (P < 0.001), the slope of the increasing portion was 0.20 +/- 0.17 less (P < 0.02), and the increase in the return cycle was 14 +/- 9 msec less (P < 0.001). These differences resulted from early activation of the site of IDC by the antidromic premature impulse when stimulating from distal sites. As a result, the coupling interval of the orthodromic impulse at the site of IDC was the same or greater than at the stimulation site. In 10 tachycardias with multiple sites of IDC, significant differences in the resetting responses did not occur even when the antidromic impulse penetrated one site of IDC.

CONCLUSION: In a fixed anatomic barrier reentrant circuit with one site of IDC, resetting distal to this site misrepresents the properties of the excitable gap of the entire circuit.}, } @article {pmid11019496, year = {2000}, author = {Nakamura, M and Shiokawa, S and Miyazaki, Y and Kita, H and Setoguchi, K and Kawahata, K and Misaki, Y and Yamamoto, K and Nishimura, J}, title = {Diffuse intervertebral disk calcification in a patient with rheumatoid arthritis.}, journal = {The journal of medical investigation : JMI}, volume = {47}, number = {3-4}, pages = {152-154}, pmid = {11019496}, issn = {1343-1420}, mesh = {Adult ; *Arthritis, Rheumatoid ; *Calcinosis ; Female ; Humans ; *Intervertebral Disc/pathology/physiopathology ; }, abstract = {A patient with seronegative rheumatoid arthritis (RA) who presented with intervertebral disk calcification (IDC) of several thoracic and lumbar intervertebral disks in herein described. There was no evidence of any other coexisting diseases such as ochronosis and hemochromatosis, but a remarkable degree of polyclonal hypergammaglobulinemia was observed as a notable finding. Although the appearance of IDC on T1-weighted images on magnetic resonance is controversial, no increased signal intensity was observed in our patient. To the best of our knowledge, this is the first report of IDC in RA.}, } @article {pmid11007434, year = {2000}, author = {Aubele, M and Cummings, M and Walsch, A and Zitzelsberger, H and Nährig, J and Höfler, H and Werner, M}, title = {Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma.}, journal = {Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology}, volume = {20}, number = {1}, pages = {17-24}, doi = {10.1155/2000/930246}, pmid = {11007434}, issn = {0921-8912}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Chromosome Aberrations ; Chromosomes/ultrastructure ; Dissection ; Female ; Histocytochemistry/*methods ; Humans ; Hyperplasia/genetics/pathology ; Lasers ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; Precancerous Conditions/genetics/pathology ; }, abstract = {There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser-microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and further processed for CGH analysis. Investigating multiple samples (n = 25) from four patients we found an average of 5.6 +/- 0.9 (mean +/- SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (+/- 0.9) aberrations was identified with 14.8 (+/- 0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples-even in all DH sample-was amplification of the 20q13 region. Our results demonstrate, that the applied combination of laser-microdissection, DOP-PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and evaluating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed. Figures on http://www.esacp.org/acp/2000/20-1/aubele. htm.}, } @article {pmid11002457, year = {2000}, author = {Ruibal, A and Arias, JI and Carmen del Río, M and San Román, JM and Lapeña, G and Schneider, J and Tejerina, A}, title = {[The cytosolic hyaluronic acid level defines several clinico-biological properties of CD44v5-positive infiltrating ductal carcinoma of the breast].}, journal = {Medicina clinica}, volume = {115}, number = {6}, pages = {201-207}, pmid = {11002457}, issn = {0025-7753}, mesh = {Adult ; Breast Neoplasms/chemistry/*diagnosis ; Carcinoma, Ductal, Breast/chemistry/*diagnosis ; Cathepsins/analysis ; Cytosol/*chemistry ; ErbB Receptors/analysis ; Female ; Humans ; Hyaluronan Receptors/*analysis ; Hyaluronic Acid/*analysis ; Immunoenzyme Techniques ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Radioimmunoassay ; Radioligand Assay ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tissue Plasminogen Activator/analysis ; }, abstract = {BACKGROUND: The hyaluronic acid (HA) is a ligand of CD44 adhesion molecule. In this work, we study if the cytosolic level of this proteoglycan can modulate certain clinical-biological properties at CD44v5-positive infiltrating ductal carcinomas (IDC) of the breast.

PATIENTS AND METHODS: We have assayed, by a radioligand method, the cytosolic level of hyaluronic acid in 127 IDC. Likewise, cytosolic levels of estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D and tissue.-type plasminogen activators (t-PA) have been dossified, as well as those of epidermal growth factor receptor (EGFR) at cell surfaces. The menopausal status, tumor size, axillary lymph node involvement, histological grade, ploidy and S-phase have also been taken into account.

RESULTS: HA positive (> 4800 ng/mg prt., which represents the median value obtained with 252 tumors) carcinomas had higher levels of PR (p = 0.035) and t-PA (p = 0.000), whereas HA negative showed a higher frequency of a tumor size > 2 cm (p = 0.015), aneuploidy (p = 0.015) and S-phase > 14% (p = 0.019), as well as histological grade 3 which reached statistical significance (p = 0.062), all of which were indicators of a worse behaviour and evolution.

CONCLUSIONS: Our results suggest that, as it also happens with that of the cell surface, cytosolic HA levels seems to modulate certain clinical-biological features of CD44v5-positive infiltrating ductal carcinomas of the breast. Likewise, they can help us to explain the discordant results described at the literature concerning its practical value when each of them are considered separately.}, } @article {pmid10988312, year = {2000}, author = {Broussas, M and Cornillet-Lefebvre, P and Bernard, J and Adjizian, JC and Potron, G and Nguyên, P}, title = {Separation of dendritic cells from highly purified human monocytes by counterflow centrifugation induces tissue factor expression.}, journal = {Transfusion}, volume = {40}, number = {9}, pages = {1088-1094}, doi = {10.1046/j.1537-2995.2000.40091088.x}, pmid = {10988312}, issn = {0041-1132}, mesh = {Animals ; Anions ; Antigens ; Cattle ; Cell Separation/*methods ; Cells, Cultured ; Centrifugation/methods ; Coagulants/metabolism ; Dendritic Cells/*cytology ; Fetal Blood/cytology ; Humans ; Monocytes/*cytology ; Phospholipids/biosynthesis ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Thromboplastin/*genetics/immunology ; }, abstract = {BACKGROUND: In vitro generation of dendritic cells (DCs) from human monocytes represents a promising tool in immunotherapy. However, it is not known whether the separation of DCs from monocytes induces tissue factor expression and therefore may trigger coagulation in patients receiving these DC preparations. The aim of this study is thus to analyze tissue factor expression on monocyte-derived DCs and to compare their ability to trigger thrombin generation to that of macrophages obtained from the same monocytes.

STUDY DESIGN AND METHODS: Human monocytes are separated by leukapheresis and washed by using counterflow centrifugation in sterile, endotoxin-free conditions. Macrophages are grown from human monocytes in the presence of GM-CSF alone and immature DCs are grown in the presence of GM-CSF plus IL-4 for 5 days with fetal calf serum (IDC-FCS). Immature DCs are also grown from human monocytes for 7 days in the presence of GM-CSF plus IL-4 with human group AB serum (IDC-HS). The addition of prostaglandin E(2) and TNFalpha in this culture medium at Day 5 leads to mature DCs (MDC-HS). Tissue factor mRNA expression is studied by RT-PCR analysis. Tissue factor antigen is measured by ELISA in cell lysates and by direct flow cytometry. The procoagulant activity of intact cells is assessed by using an amidolytic assay or a chronometric assay.

RESULTS: IDC-FCS express tissue factor mRNA and antigen and trigger thrombin generation. Procoagulant activity of IDC-FCS is dependent on both tissue factor expression and exposure to anionic phospholipid. Monocyte-derived macrophages cultured for 5 days with GM-CSF alone express lower levels of tissue factor mRNA, tissue factor antigen, and procoagulant activity than IDC-FCS. IDC-HS and MDC-HS also express high levels of tissue factor mRNA and antigen and support procoagulant activity.

CONCLUSION: Monocyte-derived DCs express a high level of functional tissue factor and support procoagulant activity. This finding should be taken into account in clinical trials.}, } @article {pmid10985175, year = {2000}, author = {Hirotsune, N and Kinugasa, K and Mandai, S and Tokunaga, K and Handa, A and Kawada, S and Ohmoto, T}, title = {Combined use of cellulose acetate polymer and retrievable platinum coils for the thrombosis of cervical carotid aneurysms.}, journal = {Acta medica Okayama}, volume = {54}, number = {4}, pages = {153-164}, doi = {10.18926/AMO/32274}, pmid = {10985175}, issn = {0386-300X}, mesh = {Aneurysm/diagnostic imaging/pathology/*therapy ; Angiography ; Animals ; Carotid Artery Diseases/diagnostic imaging/pathology/*therapy ; *Cellulose/*analogs & derivatives ; Dogs ; Embolization, Therapeutic/*instrumentation/*methods ; Neck/blood supply ; *Platinum ; *Polymers ; }, abstract = {Cellulose acetate polymer (CAP) solution is a new liquid embolic material, and it has been used clinically for the thrombosis of cerebral aneurysms. The purpose of the study was to test a method of aneurysm treatment. In an experimental model, retrievable interlocking detachable coils (IDCs) were used to create an intraaneurysmal frame or prop and then CAP was injected into 20 experimentally induced canine cervical aneurysms. Intraaneurysmal thrombosis was induced 1 week after aneurysm creation. Complete thrombosis was attempted in 12 aneurysms, and partial thrombosis was attempted in 4. Four other aneurysms served as controls. Follow-up angiography was performed for up to 8 weeks, and with the exception of 4 aneurysms, which were kept for a 2-year long-term follow-up study, the aneurysms were then harvested for histological examination. Thrombosis was successfully achieved in all cases except for 2 enlarged aneurysms that were initially partially thrombosed. No thromboembolism to distal vessels was observed. No compaction or shift of the CAP-IDC complex occurred even after 2 years. Histologically, CAP and IDCs conformed to the massive thrombotic complex without any fragmentation. By creating a frame or prop with retrievable microcoils, we were able to inject the CAP implies a comparison safely and precisely than has been previously reported. Our findings suggest that this method will be useful for the treatment of cerebral aneurysms.}, } @article {pmid10973791, year = {2000}, author = {Dietz, AB and Bulur, PA and Knutson, GJ and Matasić, R and Vuk-Pavlović, S}, title = {Maturation of human monocyte-derived dendritic cells studied by microarray hybridization.}, journal = {Biochemical and biophysical research communications}, volume = {275}, number = {3}, pages = {731-738}, doi = {10.1006/bbrc.2000.3372}, pmid = {10973791}, issn = {0006-291X}, mesh = {Antigens, CD/genetics ; *Cell Differentiation ; Cytokines/genetics ; Dendritic Cells/*cytology/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Monocytes/*cytology/*metabolism ; Neuropeptides/genetics ; Nucleic Acid Hybridization ; *Oligonucleotide Array Sequence Analysis ; RNA, Messenger/analysis/genetics ; Receptors, Cytokine/genetics ; Transcription, Genetic ; }, abstract = {We compared the transcript profiles of human myeloid immature dendritic (IDC) cells and mature dendritic cells (MDC) by hybridization of cell-derived cDNA to DNA probes immobilized on microarrays. The microarrays contained probes for 4110 known genes. We report maturation-dependent changes in transcription of clusters of differentiation, cytokines, cytokine receptors, chemokines, chemokine receptors, neuropeptides, adhesion molecules, and other genes. We identified 1124 transcripts expressed in IDC and 1556 transcripts expressed in MDC. Maturation increased the levels of 291 transcripts twofold or more and reduced the levels of 78 transcripts to one-half or less than in IDC. We identified a concerted maturation-stage-dependent transcription of the variable chains of the members of the gamma-chain-cytokine receptor family IL-4R, IL-7R, and IL-15R. Also, we found the reversal of the ratio of transcripts for galectin-3 and galectin-9 upon maturation. We identified maturation-dependent changes in the levels of transcripts for numerous genes encoding proteins previously undetected in dendritic cells such as indoleamine 2,3-deoxygenase, Epstein-Barr virus induced protein 3 and kinesin-2. Moreover, MDC transcribed and translated insulin like growth factor-1 receptor, transforming growth factor alpha, and neuropeptide Y.}, } @article {pmid10955735, year = {2000}, author = {Eriguchi, N and Aoyagi, S and Hara, M and Okuda, K and Tamae, T and Fukuda, S and Hashino, K and Sato, S and Fujiki, K and Furukawa, S and Jimi, A}, title = {Synchronous or metachronous double cancers of the pancreas and other organs: report on 12 cases.}, journal = {Surgery today}, volume = {30}, number = {8}, pages = {718-721}, pmid = {10955735}, issn = {0941-1291}, mesh = {Aged ; Carcinoma/*complications/pathology/surgery ; Colorectal Neoplasms/*pathology/surgery ; Female ; Gastrectomy ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Middle Aged ; Neoplasms, Multiple Primary/*pathology/surgery ; Neoplasms, Second Primary/*pathology/surgery ; Pancreatectomy ; Pancreatic Neoplasms/*pathology/surgery ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/*pathology/surgery ; }, abstract = {Pancreatic carcinoma carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. This retrospective study describes the results of the treatment and prognosis for double cancers in which cancer of the pancreas was associated with malignancies in other organs in 12 patients who were diagnosed and treated at Kurume University Hospital. The patients included 4 women and 8 men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous pancreatic cancers which occurred after resections of other organ malignancies. Five patients had synchronous double cancers, one of whom was diagnosed to have gastric cancer on admission. Two other patients of this group were diagnosed to have lung cancer, while the remaining 2 patients suffered from colon cancer. By the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7 patients for either gastric cancer or ulcers. In addition, one patient underwent a hysterectomy for uterine carcinoma and another received a low anterior resection for rectal carcinoma. Four of 5 patients in the synchronous group had nonresectable tumors and a palliative bypass operation was performed in 2 of these patients. Six patients who had metachronous double cancers died because of pancreatic cancer recurrence or metastases. We conclude that the prognosis of double cancers, where cancer of the pancreas is associated with other organ malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and the present study suggests the necessity of long-term follow-up examinations for gastrectomy patients in order to make an early diagnosis of pancreatic cancer.}, } @article {pmid10955380, year = {2000}, author = {Nanas, JN and Margari, ZJ and Lekakis, JP and Alexopoulos, GE and Prassopoulos, V and Agapitos, EV and Toumanidis, ST and Anastasiou-Nana, MI and Kostamis, P and Stamatelopoulos, SF}, title = {Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic dilated cardiomyopathy.}, journal = {The American journal of cardiology}, volume = {85}, number = {2}, pages = {214-220}, doi = {10.1016/s0002-9149(99)00641-4}, pmid = {10955380}, issn = {0002-9149}, mesh = {Adult ; Antibodies, Monoclonal/blood ; Cardiomyopathy, Dilated/*diagnostic imaging/immunology/physiopathology ; Follow-Up Studies ; Humans ; *Indium Radioisotopes ; Male ; Middle Aged ; Myosins/immunology ; Prognosis ; Radionuclide Imaging ; Risk Factors ; Severity of Illness Index ; Ventricular Function, Left ; }, abstract = {This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.}, } @article {pmid10952408, year = {2000}, author = {Ogawa, T and Isaji, S and Yabana, T}, title = {A case of mixed acinar-endocrine carcinoma of the pancreas discovered in an asymptomatic subject.}, journal = {International journal of pancreatology : official journal of the International Association of Pancreatology}, volume = {27}, number = {3}, pages = {249-257}, pmid = {10952408}, issn = {0169-4197}, mesh = {Carcinoma/*diagnosis/pathology ; Humans ; Immunohistochemistry ; Male ; Microscopy, Electron ; Middle Aged ; Pancreatic Neoplasms/*diagnosis/pathology ; Tomography, X-Ray Computed ; }, abstract = {A 50-yr-old Japanese man was found to have a hypoechoic mass 3 cm in diameter in the pancreatic head on an ultrasonography (US) examination without symptoms. A computed tomography (CT) scan demonstrated a 3-cm solid mass in the pancreatic head, and it was more clearly delineated as a low-density area on enhanced CT. Angiography showed a tumorlike stain, 3 cm in size, in the pancreatic head. The preoperative diagnosis was "special type of pancreatic tumor such as acinar cell carcinoma or non-functioning islet cell tumor." The patient was treated by pylorus-preserving pancreatoduodenectomy. Histological, immunohistochemical, and electron-microscopic studies of the surgical specimen led to a definitive diagnosis of a mixed acinar-endocrine carcinoma. The patient is currently well, with no signs of tumor recurrence, 18 mo after the operation. Our search of the Japanese and English-language literature retrieved only 15 well-documented cases of mixed acinar-endocrine carcinoma. Imaging in the reported cases revealed features of either acinar cell carcinoma or islet cell tumor, or both, which can may be detected even in small tumors more easily than conventional invasive ductal carcinoma of the pancreas because the detectability of this rare tumor on US and CT seems to be good.}, } @article {pmid10951489, year = {2000}, author = {Dawkins, HJ and Sellner, LN and Turbett, GR and Thompson, CA and Redmond, SL and McNeal, JE and Cohen, RJ}, title = {Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression.}, journal = {The Prostate}, volume = {44}, number = {4}, pages = {265-270}, doi = {10.1002/1097-0045(20000901)44:4<265::aid-pros1>3.0.co;2-i}, pmid = {10951489}, issn = {0270-4137}, mesh = {Adenocarcinoma/*genetics/pathology/surgery ; Alleles ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology/surgery ; Disease Progression ; Genetic Markers/genetics ; Humans ; *Loss of Heterozygosity ; Male ; Microsatellite Repeats/genetics ; Neoplasm Invasiveness ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*genetics/pathology/surgery ; Prostatic Neoplasms/*genetics/pathology/surgery ; }, abstract = {BACKGROUND: Prostate ducts and acini whose lumens are filled with malignant cells represent a well-recognized histological pattern recently termed intraductal carcinoma of the prostate (IDC-P). These tumors are often associated with rapid disease progression, and most recur after radical surgery. Controversy exists as to whether IDC-P should be recognized as a separate entity, an extension of high-grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading system. This study investigates the use of molecular markers in defining the position of IDC-P in the evolutionary hierarchy of prostate cancer progression.

METHODS: IDC-P, high-grade dysplasia, and invasive cancers from a cohort of 20 selected radical prostatectomy specimens were screened for loss of heterozygosity (LOH), using 12 polymorphic microsatellite markers frequently lost in prostate cancer.

RESULTS: LOH was absent in Gleason grade 3 cancer, infrequent in high-grade dysplasia (9%) and Gleason grade 4 cancer (29%), but common in IDC-P (60%). In IDC-P, and to a lesser extent Gleason grade 4 cancers, multiple sites of allelic loss in individual cases were usual.

CONCLUSIONS: Allelic instability provides further evidence that IDC-P is not a simple extension of dysplasia, nor does it represent invasion of Gleason grade 3 cancers into the ductal/acinar system. IDC-P and Gleason grade 4 cancer represent late but possibly separate events in prostate cancer evolution.}, } @article {pmid10948656, year = {2000}, author = {Eriguchi, N and Aoyagi, S and Hara, M and Okuda, K and Tamae, T and Fukuda, S and Hashino, K and Hashimoto, M and Sato, S and Furukawa, S and Fujiki, K and Jimi, A}, title = {A case of synchronous double cancers of the pancreas and stomach.}, journal = {The Kurume medical journal}, volume = {47}, number = {2}, pages = {169-171}, doi = {10.2739/kurumemedj.47.169}, pmid = {10948656}, issn = {0023-5679}, mesh = {Aged ; Humans ; Male ; Neoplasms, Multiple Primary/*diagnosis/pathology/surgery ; Pancreatic Neoplasms/*diagnosis/pathology/surgery ; Stomach Neoplasms/*diagnosis/pathology/surgery ; }, abstract = {Pancreatic cancer carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. We present here the case of a 76-year-old man who developed synchronous double cancers of the stomach and pancreas. He was referred to our hospital in December, 1997, with a provisional diagnosis of carcinoma of the stomach. Laboratory data on admission showed normal levels except for the serum carcinoembryonic antigen level. Abdominal ultrasonography revealed a low echoic mass anterior to the pancreas, suggestive of a nodal metastasis. Intraoperative histological findings from the pancreatic nodule confirmed a primary pancreatic cancer. The diagnosis of double cancers of the stomach and pancreas was made, and subtotal gastrectomy and distal pancreatectomy with lymph nodes dissection were carried out. The histologic sections from the stomach showed a moderately differentiated tubular adenocarcinoma, whereas those from the pancreas showed a well to moderately differentiated tubular adenocarcinoma. Double carcinomas in this association are relatively rare.}, } @article {pmid10944127, year = {2000}, author = {Pich, A and Margaria, E and Chiusa, L}, title = {Oncogenes and male breast carcinoma: c-erbB-2 and p53 coexpression predicts a poor survival.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {18}, number = {16}, pages = {2948-2956}, doi = {10.1200/JCO.2000.18.16.2948}, pmid = {10944127}, issn = {0732-183X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Analysis of Variance ; Antigens, Nuclear ; *Biomarkers, Tumor ; Breast Neoplasms, Male/*genetics/mortality ; Carcinoma, Ductal, Breast/*genetics/mortality ; Chi-Square Distribution ; Gene Expression ; Genes, erbB-2/*genetics ; Genes, p53/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Male ; Middle Aged ; Nuclear Proteins/analysis ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2/analysis ; Proto-Oncogene Proteins c-myc/analysis ; Receptor, ErbB-2/analysis ; Receptors, Androgen/analysis ; Receptors, Estrogen/analysis ; Retrospective Studies ; Risk Factors ; Statistics, Nonparametric ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53/analysis ; }, abstract = {PURPOSE: To investigate the prognostic value of biomarkers in male breast carcinoma (MBC).

PATIENTS AND METHODS: Fifty patients (mean age, 62.2 years) with invasive ductal carcinoma were retrospectively studied. All patients received surgery; 35 had adjuvant postoperative therapy. The median follow-up was 59 months (range, 1 to 230 months). c-myc, c-erbB-2, p53, and bcl-2 proteins were immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using 9E11, CB11, DO7, and bcl-2 124 monoclonal antibodies (mAbs). Estrogen, progesterone, and androgen receptors were detected using specific mAbs. Cell proliferation was assessed by MIB-1 mAb.

RESULTS: In univariate analysis, c-myc, c-erbB-2, and p53 protein overexpression was significantly correlated with prognosis. The median survival was 107 months for c-myc-negative and 52 months for c-myc-positive patients (P =.01), 96 months for c-erbB-2-negative and 39 months for c-erbB-2-positive patients (P =.02), and 100 months for p53-negative and 33 months for p53-positive patients (P =.0008). Tumor histologic grade (P =.01), tumor size (P =.02), patient age at diagnosis (P =.03), and MIB-1 scores (P =.0004) also had prognostic value. In multivariate analysis, only c-erbB-2 and p53 immunoreactivity retained independent prognostic significance. All nine patients who did not express c-erbB-2 and p53 proteins were alive after 58 months, whereas none of the 14 patients expressing both proteins survived at 61 months follow-up (P =.0002).

CONCLUSION: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.}, } @article {pmid10942102, year = {2000}, author = {Soslow, RA and Carlson, DL and Horenstein, MG and Osborne, MP}, title = {A comparison of cell cycle markers in well-differentiated lobular and ductal carcinomas.}, journal = {Breast cancer research and treatment}, volume = {61}, number = {2}, pages = {161-170}, doi = {10.1023/a:1006479113769}, pmid = {10942102}, issn = {0167-6806}, mesh = {Antigens, Neoplasm/analysis ; Antigens, Nuclear ; Biomarkers/analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/pathology ; Carcinoma, Lobular/*chemistry/pathology ; *Cell Cycle ; Cell Cycle Proteins/*analysis ; Cohort Studies ; Cyclin D1/analysis ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunophenotyping ; Ki-67 Antigen ; Microtubule-Associated Proteins/analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins/*analysis ; Nuclear Proteins/analysis ; Proto-Oncogene Proteins/analysis ; Proto-Oncogene Proteins c-bcl-2/analysis ; Proto-Oncogene Proteins c-mdm2 ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Tumor Suppressor Protein p53/analysis ; *Tumor Suppressor Proteins ; }, abstract = {Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom-Richardson Grade I). We believe that different antigen expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigens in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.}, } @article {pmid10939434, year = {2000}, author = {Rokutanda, N and Iino, Y and Yokoe, T and Maemura, M and Horiguchi, J and Takei, H and Koibuchi, Y and Iijima, K and Oyama, T and Morishita, Y}, title = {Primary squamous cell carcinoma of the breast during lactation: a case report.}, journal = {Japanese journal of clinical oncology}, volume = {30}, number = {6}, pages = {279-282}, doi = {10.1093/jjco/hyd069}, pmid = {10939434}, issn = {0368-2811}, mesh = {Adult ; Breast Neoplasms/*etiology/pathology/physiopathology ; Carcinoma, Squamous Cell/*etiology/physiopathology/secondary ; Female ; Humans ; *Lactation ; Lung Neoplasms/secondary ; }, abstract = {A case of primary squamous cell carcinoma of the breast during lactation is reported. The patient was a 32-year-old woman, in post-partum lactating 18 months after delivery, who was referred to our hospital following detection of a lump in her left breast during physical examination in mass screening for breast cancer. The tumor, palpated in the upper outer quadrant of the left breast, was firm, well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular-shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed tumor. Based on these findings, breast cancer was suspected and an excisional biopsy was performed. The resected specimen was a firm, solid and circumscribed tumor with central hemorrhage. Microscopic findings demonstrated that the tumor consisted of an invasive ductal carcinoma with marked squamous metaplasia, such as keratinization and squamo-columnar junction. Breast-conserving surgery was performed and no lymph node involvement was noted. Both estrogen and progesterone receptors of the tumor were negative. Generally, the size of both squamous cell carcinoma and carcinoma during the lactation period tends to be larger than ordinary carcinomas. In this case, the cancerous lesion was detected at a relatively early stage. Although the cancerous lesion was detected at a relatively early stage and no lymph node involvement was noted, lung metastases occurred within 12 months of the surgery. Malignant potential is generally considered to be high in cases of squamous cell carcinoma of the breast with lactation and thus intensive treatment potentially resulting in severe side effects was considered to be necessary for this patient.}, } @article {pmid10935476, year = {1999}, author = {Rogers, MS and Foley, MA and Crotty, TB and Hartmann, LC and Ingle, JN and Roche, PC and Strehler, EE}, title = {Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development.}, journal = {Neoplasia (New York, N.Y.)}, volume = {1}, number = {3}, pages = {220-225}, pmid = {10935476}, issn = {1522-8002}, support = {T32 CA075926/CA/NCI NIH HHS/United States ; P20 CA 65800-01/CA/NCI NIH HHS/United States ; T32CA75926/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*chemistry ; Calmodulin/*analysis/genetics/physiology ; Down-Regulation ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Rabbits ; }, abstract = {Cell proliferation requires calmodulin, a protein that regulates calcium-dependent enzymes involved in signal transduction pathways in eukaryotic cells. Calmodulin-like protein (CLP) is found in certain epithelial cell types, including normal breast epithelium, and, although it closely resembles calmodulin in amino acid sequence, CLP interacts with different proteins than does calmodulin. The observation that CLP mRNA expression is dramatically reduced in transformed breast epithelial cells led to two hypotheses: (1) CLP helps to maintain the differentiated state in epithelial cells; and (2) downregulation of CLP accompanies malignant transformation of breast epithelial cells. The objective of this study was to determine if the expression of CLP in human breast cancer specimens is reduced in comparison to its expression in normal breast tissue. Eighty human breast cancer biopsy specimens were analyzed immunohistochemically for CLP expression by using a polyclonal rabbit antihuman CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal carcinoma in-situ specimens, compared with normal breast specimens. None of the breast cancer specimens showed an increase in CLP expression. These findings support the hypotheses that CLP behaves as a functional tumor suppressor protein and is downregulated early in breast cancer progression.}, } @article {pmid10930114, year = {2000}, author = {Lo, YF and Chen, TC and Chen, SC and Chao, CC}, title = {Aberrant expression of TSG101 in Taiwan Chinese breast cancer.}, journal = {Breast cancer research and treatment}, volume = {60}, number = {3}, pages = {259-266}, doi = {10.1023/a:1006426400524}, pmid = {10930114}, issn = {0167-6806}, mesh = {Blotting, Western ; Breast Neoplasms/ethnology/*genetics/metabolism ; China/ethnology ; DNA Primers/chemistry ; DNA-Binding Proteins/biosynthesis/*genetics ; Endosomal Sorting Complexes Required for Transport ; Female ; Gene Expression/genetics ; Humans ; Immunohistochemistry ; Leucine Zippers/*genetics ; Neoplasm Staging ; RNA, Messenger/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Deletion ; Taiwan/epidemiology ; Transcription Factors/biosynthesis/*genetics ; }, abstract = {Functional inactivation of the tsg101 gene in mouse fibroblasts results in cell transformation and the ability to form metastatic tumors in nude mice. The human tsg101 gene was mapped to chromosome 11q15.1-2 and found to mutate in some cancer patients. To test the expression pattern of the tsg 101 gene in Chinese breast cancer patients, we analyzed the mRNA by RT-PCR in 51 breast cancer patients. The full-length tsg101 and 7 truncated transcripts were detected in both normal and matched tumor tissues. A short transcript with a deletion of nucleotides 154-1054 is frequently presented in late-stage breast cancers. TSG101 protein expression was also detected by Western blot analysis in 30 breast cancer patients. A predicted full-length 46 kDa and three proteins with smaller molecular weight were detected. The full-length 46 kDa protein was less expressed in tumor specimens. Immunohistochemical stains from 10 patients of each stage 0-4 revealed that TSG101 protein was predominantly present in the cytoplasm. Cell nuclei were occasionally immunopositive and the chromosomes were deeply stained during cell division. The intracellular location and the expression of TSG101 protein were both not stage-dependent in primary breast cancers. In addition, normal mammary glands were more homogenously immunopositive than invasive ductal carcinoma. These results support the notion that the aberrant expression of TSG101 in breast cancer is associated with altered cell growth.}, } @article {pmid10929825, year = {2000}, author = {Shahnavaz, H}, title = {Role of ergonomics in the transfer of technology to industrially developing countries.}, journal = {Ergonomics}, volume = {43}, number = {7}, pages = {903-907}, doi = {10.1080/001401300409099}, pmid = {10929825}, issn = {0014-0139}, mesh = {*Developing Countries ; *Ergonomics ; Humans ; Man-Machine Systems ; Risk Factors ; Technology Assessment, Biomedical ; *Technology Transfer ; }, abstract = {Technological development has contributed to economic growth and social progress as well as a reduction of many sources of occupational accidents, injuries and stresses. However, advanced technology has also brought new sources of work stress and injuries. Industrially developing countries (IDC) have tended to try to achieve economic growth and development by importing technology designed for IDC. However, because of several complex technical, cultural and socio-economic factors, this policy has not been always successful. Inappropriate technology transfer has led to many work environment and productivity problems. Consideration of ergonomics in the choice and utilization of the transferred technology can help to create a good fit between technology, technology users and the operating environment. Application of ergonomics is, however, not widely spread in most IDC. Ergonomics input will create the appropriate working environment in which people are safe and motivated to participate and can better utilize company resources for increasing system productivity, reliability and availability.}, } @article {pmid10921297, year = {2000}, author = {Yasumura, K and Ogawa, K and Yuasa, Y and Hiramatsu, H and Hiramatsu, K and Kitajima, M}, title = {[Dynamic MRI and tumor angiogenesis of breast cancer].}, journal = {Nihon Igaku Hoshasen Gakkai zasshi. Nippon acta radiologica}, volume = {60}, number = {7}, pages = {379-388}, pmid = {10921297}, issn = {0048-0428}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*blood supply/diagnosis/metabolism ; Carcinoma, Ductal, Breast/*blood supply/diagnosis/metabolism ; Endothelial Growth Factors/analysis ; Female ; Humans ; Lymphokines/analysis ; *Magnetic Resonance Imaging ; Middle Aged ; Neovascularization, Pathologic/*diagnosis ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {The purpose of this study was to clarify the mechanism underlying early enhanced MR images of breast cancer by dynamic MR imaging from the aspect of tumor angiogenesis. The images depicted by dynamic MR imaging of breast cancer were divided into the following two groups: a marginal strong enhancement (MSE) pattern and a variable pattern without marginal strong enhancement (non-MSE). Twenty patients with invasive ductal carcinoma (maximum diameter < 2 cm) were examined by dynamic MR imaging, and the histological materials were submitted to two-dimensional computer image analysis with immunohistochemistry and histochemistry; morphological microvessel characteristics and microvessel density were examined; and the expression of vascular endothelial growth factor (VEGF) was investigated. In the MSE cases, vessel wall irregularity of capillaries and venules in the peripheral area adjacent to the tumor correlated (p < 0.001) with the enhancement pattern, and the total microvessel density (especially of arterioles with a maximum diameter less than 50 microns) of the peripheral area adjacent to the tumor was significantly higher than that of the tumor area. However, in the non-MSE cases, total microvessel density showed no significant difference between the peripheral area adjacent to the tumor and the tumor area, whereas the capillary density of the tumor area was four times greater than that of the peripheral area adjacent to the tumor. The expression of VEGF was strongly positive for the tumor nest adjacent to the capillaries. These results suggest that the enhanced images of the MSE pattern depend on abundant blood supply from arterioles and that the images of the non-MSE pattern might be reflective of angiogenic activity including variable VEGF expression of tumor cells. Thus the mechanism underlying early dynamic MR images of breast cancer was a complex result of tumor angiogenesis and the microcirculatory environment.}, } @article {pmid10921219, year = {1999}, author = {Sikka, M and Agarwal, S and Bhatia, A}, title = {Interobserver agreement of the Nottingham histologic grading scheme for infiltrating duct carcinoma breast.}, journal = {Indian journal of cancer}, volume = {36}, number = {2-4}, pages = {149-153}, pmid = {10921219}, issn = {0019-509X}, mesh = {Biopsy/standards ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Female ; Guidelines as Topic ; Humans ; Observer Variation ; }, abstract = {Interobserver agreement of the histologic grading scheme for infiltrating duct carcinoma (IDC) of breast was assessed. Three pathologists independently evaluated histologic grade using the modified Bloom and Richardson histological grading system on 40 cases of IDC breast. Pairwise K value for agreement ranged from 0.68-0.83 (median 0.68) for histological grade suggesting substantial agreement. Generalized K values were 0.54, 0.34 and 0.36 for tubule formation, nuclear pleomorphism and mitotic count respectively indicating moderate and fair agreement. Similar levels of agreement were obtained specially in the final histologic grade between pathologists routinely reporting histopathology material and one pathologist who was not. This was achieved by use of precise guidelines. The ease with which this grading system could be applied by pathologists on histopathology material will greatly help its acceptability in routine histopathology.}, } @article {pmid10915850, year = {2000}, author = {Rouard, H and Léon, A and Klonjkowski, B and Marquet, J and Tennezé, L and Plonquet, A and Agrawal, SG and Abastado, JP and Eloit, M and Farcet, JP and Delfau-Larue, MH}, title = {Adenoviral transduction of human 'clinical grade' immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity.}, journal = {Journal of immunological methods}, volume = {241}, number = {1-2}, pages = {69-81}, doi = {10.1016/s0022-1759(00)00214-3}, pmid = {10915850}, issn = {0022-1759}, mesh = {Adenoviridae ; Antigen Presentation ; Antigens, CD ; *Cancer Vaccines ; Cell Differentiation ; Cell Separation/methods ; Cells, Cultured ; Culture Techniques/*methods ; Dendritic Cells/*cytology/*immunology ; Gene Transfer Techniques ; Genetic Vectors ; HLA-DR Antigens/biosynthesis ; Humans ; Immunoglobulins/biosynthesis ; Leukapheresis ; Lymphocyte Culture Test, Mixed ; Membrane Glycoproteins/biosynthesis ; Recombinant Proteins/immunology ; T-Lymphocytes/immunology ; *Transgenes ; beta-Galactosidase/genetics/immunology ; }, abstract = {The therapeutic use of dendritic cells (DC) in antigen-specific anti-tumor vaccines, requires sufficient numbers of functional DC, the preparation of which should comply with the code of Good Manufacturing Practice. In addition, the expression of tumor specific antigen should be possible in these DC. As a preclinical step, the method reported here was developed in healthy volunteers. Monocytes (Mo) were isolated by leukapheresis from 12 donors, purified by elutriation and then cultured for 6 days in sealed bags in AIM-V serum free medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13). Between 6x10(8) and 1x10(9) immature DC (iDC) could be differentiated from one leukapheresis. Cells displayed a characteristic iDC phenotype (CD1a(+), CD14(-), CD80(+), CD86(+), HLA DR(+), CD83(-)), and had potent allogeneic and antigen dependent autologous T cell-stimulatory capacity. Moreover, iDC could be further differentiated into mature DC by CD40 ligation as assessed by CD83 expression and the upregulation of HLA-DR and costimulatory molecules. After infection with a recombinant adenovirus encoding for beta-galactosidase (betaGal), 50% to 80% of iDC expressed betaGal without toxicity. Adenovirus infection increased the expression of both costimulatory molecules and CD83, and also increased allogeneic stimulatory capacity. Thus, the method developed here allows us to use large numbers of functional iDC as will be required for therapeutic uses in man. These DC can express a transgenic protein.}, } @article {pmid10914818, year = {2000}, author = {Shen, KL and Yang, LS and Hsieh, HF and Chen, CJ and Yu, JC and Tsai, NM and Harn, HJ}, title = {Microsatellite alterations on human chromosome 11 in in situ and invasive breast cancer: a microdissection microsatellite analysis and correlation with p53, ER (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity.}, journal = {Journal of surgical oncology}, volume = {74}, number = {2}, pages = {100-107}, doi = {10.1002/1096-9098(200006)74:2<100::AID-JSO5>3.0.CO;2-O}, pmid = {10914818}, issn = {0022-4790}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/chemistry/*genetics ; Carcinoma in Situ/chemistry/*genetics ; Carcinoma, Ductal, Breast/chemistry/*genetics ; *Chromosomes, Human, Pair 11 ; Female ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; *Microsatellite Repeats ; Middle Aged ; Mutation ; Neoplasm Proteins/immunology ; Receptors, Estrogen/*metabolism ; Receptors, Progesterone/*metabolism ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been documented in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromosome 11 loci in breast cancer is a frequent event. The purpose of the present study is to examine the incidence of microsatellite alterations in in situ and invasive human breast carcinoma and to clarify their significance in regulating the dynamics of cancer progression.

METHODS: Four highly polymorphic (CA)n repeat microsatellites were used to determine microsatellite alterations in ten ductal carcinoma in situ (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of p53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI, immunohistochemistry staining was applied.

RESULTS: MSI were detected in 20% (2/10) of DCIS and in 47.4% (9/19) of IDC. The frequency of MSI in IDC was significantly higher than that in DCIS (P < 0.001). Also, the MSI seemed to correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not histological grade or age. In addition, we found that 27% of the tumors showed LOH at 11q23.3-24 region between loci D11S934 and D11S912. Seven of nine MSI cases demonstrated low or no expression of p53. However, there was significantly reduced expression of PR, but not ER in MSI cases.

CONCLUSIONS: Our results suggest that breast cancer acquires the RER phenotype (replication-error phenotype) in the relatively late stages, and that the RER phenotype is associated with aggressiveness of IDC (infiltrative duct carcinoma). The result also implicated that mismatch repair failure can alter the expression of PR but not ER and p53.}, } @article {pmid10908085, year = {2000}, author = {Noori, A and Lindenfeld, J and Wolfel, E and Ferguson, D and Bristow, MR and Lowes, BD}, title = {Beta-blockade in adriamycin-induced cardiomyopathy.}, journal = {Journal of cardiac failure}, volume = {6}, number = {2}, pages = {115-119}, pmid = {10908085}, issn = {1071-9164}, mesh = {Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Antineoplastic Agents/*adverse effects ; Carbazoles/therapeutic use ; Cardiomyopathies/chemically induced/*drug therapy/physiopathology ; Cardiomyopathy, Dilated/drug therapy/physiopathology ; Carvedilol ; Doxorubicin/*adverse effects ; Female ; Humans ; Male ; Metoprolol/therapeutic use ; Middle Aged ; Myocardial Contraction/drug effects ; Neoplasms/drug therapy ; Propanolamines/therapeutic use ; Propranolol/therapeutic use ; Retrospective Studies ; Stroke Volume/drug effects ; }, abstract = {Beta-blockade consistently improves myocardial systolic function in patients with both nonischemic and ischemic cardiomyopathy. The effects of beta-blockade on Adriamycin-induced cardiomyopathy (ACM), however, are unknown. We retrospectively evaluated the effects of beta-blockade on patients with ACM by using a case-controlled design. The control group consisted of 16 consecutively chosen age- and sex-matched patients with idiopathic dilated cardiomyopathy (IDC) who were treated with beta-blockers. Patients with ACM had a baseline mean left ventricular ejection fraction (LVEF) of 28%, which improved to 41% (P = .041) after treatment with beta-blockers. The control group had a baseline mean LVEF of 26%, which improved to 32% (P = .015) after treatment. The mean duration of beta-blocker therapy in the Adriamycin and control groups was 8 and 9 months, respectively. The degree of improvement between the 2 groups was not significantly different. Beta-blockers have a beneficial effect on cardiac function in patients with ACM, which is at least comparable with other forms of heart failure with systolic dysfunction.}, } @article {pmid10907931, year = {2000}, author = {Kleer, CG and Michael, CW}, title = {Fine-needle aspiration of breast carcinomas with prominent lymphocytic infiltrate.}, journal = {Diagnostic cytopathology}, volume = {23}, number = {1}, pages = {39-42}, doi = {10.1002/1097-0339(200007)23:1<39::aid-dc9>3.0.co;2-#}, pmid = {10907931}, issn = {8755-1039}, mesh = {Adult ; Biopsy, Needle/methods ; Breast Neoplasms/classification/*pathology ; Carcinoma, Ductal, Breast/classification/*pathology ; Carcinoma, Medullary/classification/*pathology ; Female ; Follow-Up Studies ; Humans ; *Lymphocytes, Tumor-Infiltrating/immunology ; Middle Aged ; }, abstract = {Carcinomas of the breast with prominent lymphoplasmacytic background are commonly encountered in cytology. The aim of this study was to assess the prevalence of different types of carcinomas that share this common feature, identify possible distinguishing cytologic features, and evaluate the diagnostic pitfalls in this group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation was absent in the TMC but was common in IDC and AMC. No cytologic differences were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes and plasma cells may be seen in different types of breast carcinomas and should not be considered a diagnostic feature of TMC. Features potentially helpful in the cytologic differential diagnosis of a carcinoma with prominent lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2 microm in IDC and AMC, respectively) and the degree of nuclear atypia. Lymphocytosis may be part of the carcinoma or may originate from a lymph node involved by metastases. In rare cases, a prominent neutrophilic infiltrate may also be present.}, } @article {pmid10905514, year = {2000}, author = {Zhang, R and Zhang, H and Wei, H and Luo, X}, title = {Expression of metallothionein in invasive ductal breast cancer in relation to prognosis.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {19}, number = {1-2}, pages = {95-97}, pmid = {10905514}, issn = {0731-8898}, mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis ; Breast Neoplasms/diagnosis/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/diagnosis/*metabolism/mortality/pathology ; Female ; Humans ; Immunohistochemistry ; Metallothionein/*biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; }, abstract = {The aim of this study was to assess the presence and clinical significance of metallothionein (MT) in primary invasive ductal carcinoma of the breast. We investigated 96 cases of routinely fixed and paraffin-embedded primary breast carcinomas with the immunohistochemical method. Positive staining for MT was observed in 52.1% of specimen. In most cases both nuclear and cytoplasmic staining was seen. A statistically significant association was found between MT-positive staining and nuclear grade (p < 0.01). MT-positive cases had a significantly poorer prognosis when compared with the MT-negative cases (p < 0.01). We concluded that the MT expression may be of a prognostic value for primary invasive ductal carcinoma of the breast and is possibly an indicator of more aggressive and less differentiated carcinoma cells.}, } @article {pmid10904838, year = {2000}, author = {Grimm, W and Hoffmann, J and Menz, V and Müller, HH and Maisch, B}, title = {Prediction of major arrhythmic events and sudden cardiac death in dilated cardiomyopathy. The Marburg Cardiomyopathy Study design and description of baseline clinical characteristics.}, journal = {Herz}, volume = {25}, number = {3}, pages = {189-199}, doi = {10.1007/s000590050006}, pmid = {10904838}, issn = {0340-9937}, mesh = {Adolescent ; Adult ; Aged ; Atrial Fibrillation/*diagnosis/physiopathology ; Bundle-Branch Block/*diagnosis/physiopathology ; Cardiomyopathy, Dilated/*diagnosis/physiopathology ; Death, Sudden, Cardiac/*etiology/prevention & control ; Electrocardiography, Ambulatory ; Female ; Follow-Up Studies ; Heart Failure/diagnosis/physiopathology ; Hemodynamics/physiology ; Humans ; Male ; Middle Aged ; Pressoreceptors/physiopathology ; Prospective Studies ; Risk Factors ; Signal Processing, Computer-Assisted ; Ventricular Fibrillation/*diagnosis/physiopathology ; }, abstract = {The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study designed to determine the value of the following potential non-invasive arrhythmia risk predictors in more than 200 patients with idiopathic dilated cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association functional class, left ventricular end-diastolic diameter and ejection fraction, left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on 24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This report describes the rationale of MACAS as well as the clinical characteristics of the first 236 patients enrolled between March 1996 and October 1999. The prognostic significance of the potential arrhythmia risk predictors in MACAS will be determined by multivariate Cox analysis at the end of 5-year follow-up. Primary endpoints are total mortality and major arrhythmic events defined as sustained ventricular tachycardia, ventricular fibrillation or sudden cardiac death. The results of MACAS will have important implications for the design of future studies evaluating the role of prophylactic defibrillator therapy in idiopathic dilated cardiomyopathy.}, } @article {pmid10903870, year = {2000}, author = {Mallorquí-Fernández, G and Pous, J and Peracaula, R and Aymamí, J and Maeda, T and Tada, H and Yamada, H and Seno, M and de Llorens, R and Gomis-Rüth, FX and Coll, M}, title = {Three-dimensional crystal structure of human eosinophil cationic protein (RNase 3) at 1.75 A resolution.}, journal = {Journal of molecular biology}, volume = {300}, number = {5}, pages = {1297-1307}, doi = {10.1006/jmbi.2000.3939}, pmid = {10903870}, issn = {0022-2836}, mesh = {Amino Acid Sequence ; Arginine/metabolism ; Binding Sites ; Blood Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Disulfides/metabolism ; *Eosinophil Cationic Protein ; Eosinophil Granule Proteins ; Eosinophils/*enzymology ; Escherichia coli ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/genetics/metabolism ; Ribonucleases/*chemistry/genetics/metabolism ; Sequence Alignment ; Static Electricity ; Structure-Activity Relationship ; }, abstract = {Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The protein has been cloned, heterologously overexpressed, purified and crystallized. Its crystal structure has been determined and refined using data up to 1. 75 A resolution. The molecule displays the alpha+beta folding topology typical for members of the ribonuclease A superfamily. The catalytic active site residues are conserved with respect to other ribonucleases of the superfamily but some differences appear at substrate recognition subsites, which may account, in part, for the low catalytic activity. Most strikingly, 19 surface-located arginine residues confer a strong basic character to the protein. The high concentration of positive charges and the particular orientation of the side-chains of these residues may also be related to the low activity of ECP as a ribonuclease and provides an explanation for its unique cytotoxic role through cell membrane disruption.}, } @article {pmid10896736, year = {2000}, author = {Siqueland, L and Crits-Christoph, P and Barber, JP and Butler, SF and Thase, M and Najavits, L and Onken, LS}, title = {The role of therapist characteristics in training effects in cognitive, supportive-expressive, and drug counseling therapies for cocaine dependence.}, journal = {The Journal of psychotherapy practice and research}, volume = {9}, number = {3}, pages = {123-130}, pmid = {10896736}, issn = {1055-050X}, support = {K02-MH00756/MH/NIMH NIH HHS/United States ; P50-MH-45178/MH/NIMH NIH HHS/United States ; U18-DA07090/DA/NIDA NIH HHS/United States ; }, mesh = {Adult ; Cocaine-Related Disorders/psychology/*rehabilitation ; Cognitive Behavioral Therapy/*education ; Curriculum ; Female ; Humans ; Male ; Middle Aged ; Professional Competence ; Psychoanalytic Therapy/*education ; *Psychotherapeutic Processes ; Psychotherapy/*education ; Treatment Outcome ; }, abstract = {The role of therapist characteristics in therapy training was examined for 62 therapists in a multisite psychotherapy outcome study that included cognitive therapy (CT), supportive-expressive (SE) psychodynamic therapy, and individual drug counseling (IDC) for cocaine-dependent patients. Demographic variables and experience and competence ratings prior to training were correlated with measures of change in competence during the training phase. Higher competence ratings before training were associated with greater change in competence for SE and higher average competence for IDC. More years of experience were associated with greater change in competence for CT therapists, but more hours of pre-training supervision in the CT treatment modality were associated with less change.}, } @article {pmid10892294, year = {2000}, author = {Nakano, S and Tsuruta, J and Iyama, K}, title = {[Remodeling of basement membrane in association with cancer invasion].}, journal = {Rinsho byori. The Japanese journal of clinical pathology}, volume = {48}, number = {5}, pages = {451-457}, pmid = {10892294}, issn = {0047-1860}, mesh = {Basement Membrane/metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Collagen/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Neoplasm Invasiveness ; RNA, Messenger/metabolism ; }, abstract = {Type IV collagen the major component of basement membrane (BM), is composed of six genetically distinct alpha chains. In normal breast tissue, benign breast tumors, and in the intraductal components of invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were stained in all BM, whereas alpha 5 (IV) and alpha 6 (IV) chains were restrictively localized in a linear pattern in the epithelial BM. However, in invasive ductal carcinoma, alpha 1 (IV) and alpha 2 (IV) chains were discontinuously or negatively stained in the cancer cell nest, and the assembly of alpha 5 (IV) and alpha 6 (IV) chains into the BM was completely inhibited. The results indicate that the mammary gland forms a second network of BM composed of alpha 5 (IV)/alpha 6 (IV) chains, in addition to the classic network of alpha 1 (IV)/alpha 2 (IV) chains. Remodeling of type IV collagen alpha chains during the development of invasive breast cancer seems to be differentially regulated, and to be associated with modification of histopathological findings.}, } @article {pmid10886733, year = {2000}, author = {Umekita, Y and Yoshida, H}, title = {Cyclin D1 expression in ductal carcinoma in situ, atypical ductal hyperplasia and usual ductal hyperplasia: an immunohistochemical study.}, journal = {Pathology international}, volume = {50}, number = {7}, pages = {527-530}, doi = {10.1046/j.1440-1827.2000.01076.x}, pmid = {10886733}, issn = {1320-5463}, mesh = {Breast Neoplasms/*metabolism/pathology ; Carcinoma in Situ/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/secondary ; Cyclin D1/*metabolism ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Hyperplasia/metabolism/pathology ; Immunoenzyme Techniques ; Lymph Nodes/metabolism/pathology ; Lymphatic Metastasis/pathology ; Neoplasm Staging ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {The cell cycle regulatory gene, Cyclin D1, plays a critical role in the growth and progression of several types of human cancer, including breast cancer. Immunohistochemical study of Cyclin D1 expression has been extensively reported in invasive ductal carcinoma (IDC). In contrast, there have been few reports concerning Cyclin D1 expression in ductal carcinoma in situ (DCIS) and their positive rates are variable. The differences in the reported frequency may be largely due to the differences in antibodies used, immunohistochemical methods and the positive cut-off point. However, we speculated that the strictness of diagnosis of DCIS might be somewhat responsible for these differences in frequency. Therefore, we selected cases of DCIS by carefully eliminating cases of predominantly intraductal carcinoma (PIC). Moreover, to clarify whether Cyclin D1 expression is involved in multistep carcinogenesis or the progression of human breast cancer, we immunohistochemically investigated Cyclin D1 expression in 57 DCIS, 10 atypical ductal hyperplasia (ADH), 70 usual ductal hyperplasia (UDH), 44 PIC and 92 IDC. Cyclin D1 expression was detected in 41 DCIS cases (72%), 22 PIC cases (50%) and 40 IDC cases (43%). No expression of Cyclin D1 was observed in either ADH or UDH. There were no significant correlations between Cyclin D1 expression and histological grade or estrogen receptor expression in DCIS. These results suggest that Cyclin D1 expression may play an important role in the early stages of carcinogenesis, and that immunohistochemical detection of Cyclin D1 expression may be helpful in differentiating low-grade DCIS from ADH.}, } @article {pmid10880771, year = {2000}, author = {Ando, Y and Iwase, H and Ichihara, S and Toyoshima, S and Nakamura, T and Yamashita, H and Toyama, T and Omoto, Y and Karamatsu, S and Mitsuyama, S and Fujii, Y and Kobayashi, S}, title = {Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.}, journal = {Cancer letters}, volume = {156}, number = {2}, pages = {207-214}, doi = {10.1016/s0304-3835(00)00467-5}, pmid = {10880771}, issn = {0304-3835}, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; DNA, Neoplasm/genetics/isolation & purification ; Female ; Humans ; *Loss of Heterozygosity ; *Microsatellite Repeats ; Middle Aged ; Paraffin Embedding ; Polymerase Chain Reaction ; Receptors, Estrogen/physiology ; }, abstract = {To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.}, } @article {pmid10879734, year = {2000}, author = {Jones, C and Foschini, MP and Chaggar, R and Lu, YJ and Wells, D and Shipley, JM and Eusebi, V and Lakhani, SR}, title = {Comparative genomic hybridization analysis of myoepithelial carcinoma of the breast.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {80}, number = {6}, pages = {831-836}, doi = {10.1038/labinvest.3780087}, pmid = {10879734}, issn = {0023-6837}, mesh = {Aged ; Breast Neoplasms/*genetics/pathology ; *Chromosome Aberrations ; Chromosome Mapping ; Female ; Humans ; Karyotyping ; *Loss of Heterozygosity ; Middle Aged ; Myoepithelioma/*genetics/pathology ; Nucleic Acid Hybridization/methods ; Polymerase Chain Reaction ; Retrospective Studies ; }, abstract = {Although there seems to be a common stem cell for the two epithelial cell types in the breast, the vast majority of breast cancers exhibit a luminal phenotype. Pure myoepithelial carcinomas are rare. We report our findings of genetic alterations in these tumors. We have analyzed 10 cases of pure myoepithelial cell carcinomas using laser capture microdissection and comparative genomic hybridization. The mean number of changes was 2.1 (range 0-4), compared with a mean of 8.6 (range 3.6-13.8) in unselected ductal carcinomas. Common alterations included loss at 16q (3/10 cases), 17p (3/10), 11q (2/10), and 16p (2/10), regions also commonly deleted in ductal carcinomas. The single case in which both pure myoepithelial carcinoma and invasive ductal carcinoma was present showed 2 alterations in the myoepithelial tumor (losses at 17p and 17q), whereas the invasive ductal component showed 15 alterations (5 gains and 9 losses), including loss at 17p. The sharing of 17p loss in myoepithelial and ductal carcinoma is consistent with a common stem cell model in the breast. The relatively few genetic alterations in otherwise aggressive neoplasms suggests that myoepithelial tumors may be a good model for the delineation of genes important in breast tumorigenesis.}, } @article {pmid10874262, year = {2000}, author = {Grimm, W and Glaveris, C and Hoffmann, J and Menz, V and Müller, HH and Hufnagel, G and Maisch, B}, title = {Arrhythmia risk stratification in idiopathic dilated cardiomyopathy based on echocardiography and 12-lead, signal-averaged, and 24-hour holter electrocardiography.}, journal = {American heart journal}, volume = {140}, number = {1}, pages = {43-51}, doi = {10.1067/mhj.2000.107178}, pmid = {10874262}, issn = {0002-8703}, mesh = {Adolescent ; Adult ; Aged ; Analysis of Variance ; Cardiomyopathy, Dilated/*diagnosis/*mortality/physiopathology ; Death, Sudden, Cardiac/*epidemiology ; Echocardiography/*methods ; Electrocardiography, Ambulatory/*methods ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Probability ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Risk Factors ; Survival Analysis ; Ventricular Fibrillation/*diagnosis/*epidemiology ; }, abstract = {BACKGROUND: To date, considerable controversy exists regarding noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC). Methods and Results Between 1992 and 1997, 202 patients with IDC without a history of sustained ventricular tachycardia (VT) underwent echocardiography, signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major arrhythmic events, including sustained VT, ventricular fibrillation, or sudden death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and nonsustained VT on Holter as the only independent arrhythmia risk predictors. The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was associated with a 14. 3-fold risk for future arrhythmic events (95% confidence interval 2. 3-90). To further elucidate the prognostic value of LV ejection fraction, multivariate Cox analysis was repeated with ejection fraction forced to remain in the model. In the latter model, an ejection fraction
CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT on Holter, and the combination of LV ejection fraction
METHODS: Age specific and age-adjusted breast carcinoma incidence rates from 1977-1995 were obtained from the nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Three histologic groupings were used: lobular, ductal, and all invasive breast carcinomas. Overall incidence rates for each grouping, as well as for each stage (local, regional, and distant), were obtained.

RESULTS: The rate of incidence of lobular carcinoma increased steadily from 1977-1995 in women age >/= 50 years whereas it remained stable in women age < 50 years. Alternatively, the rate of incidence of ductal carcinoma increased steadily from 1977-1987, but from 1987-1995 it remained relatively constant across all age groups.

CONCLUSIONS: The incidence rates of invasive lobular breast carcinomas increased steadily since 1977 whereas the incidence rates of invasive ductal carcinoma have plateaued since 1987. This rise occurred specifically among women age >/= 50 years and may be related to postmenopausal status. Further epidemiologic, clinical, and laboratory research is required to assess what factors are contributing to this trend.}, } @article {pmid11091573, year = {1997}, author = {Akashi-Tanaka, S and Fukutomi, T and Miyakawa, K and Tsuda, H}, title = {Diagnostic Value of Enhanced Computed Tomography in the Detection of the Widely Spreading Intraductal Component of Breast Cancer: Case Reports.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {4}, number = {1}, pages = {29-32}, doi = {10.1007/BF02967052}, pmid = {11091573}, issn = {1880-4233}, abstract = {We report cases of breast cancer with extensive intraductal component (EIC), the extent of which could be detected only by contrast-enhanced computed tomography (CT) scan. One case was a 32-year-old woman who presented left nipple bloody discharge without breast mass palpation. Mammography (MMG), galactography and ultrasonography (US) showed no abnormalities. Contrast helical CT scan revealed numerous patchy enhancement in the upper-outer quadrant of the left breast. Histological examnation revealed invasive ductal carcinoma with a predominant intraductal component. The second case was a 36- year-old woman who had noticed a left breast mass 2.4 cm in diameter. MMG and US suggested a localized breast cancer. Contrast helical CT scan revealed numerous patchy enhancement throughout the mammary gland in addition to the index tumor near the nipple. Histopathological results indicated invasive ductal carcinoma with widely spread ELC. In these two cases, the extent of intraductal cancer also correlated well with the CT findings. Breast CT scan can be an effective tool for determining the extent of the intraductal component of breast cancer, which is an important factor when considering breast-conserving therapy.}, } @article {pmid10868038, year = {1997}, author = {Peng, J and Dubreuil, A and Raverdy, N and Ganry, O and Lorriaux, A}, title = {[Epidemiology of breast cancers in the Somme department (1990-1993)].}, journal = {Annales de chirurgie}, volume = {51}, number = {9}, pages = {974-980}, pmid = {10868038}, issn = {0003-3944}, mesh = {Adult ; Aged ; Breast Neoplasms/*epidemiology/pathology ; Carcinoma, Ductal, Breast/epidemiology ; Carcinoma, Lobular/epidemiology ; Female ; France/epidemiology ; Humans ; Incidence ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Rural Population ; Survival Rate ; Urban Population ; }, abstract = {Breast cancer is the commonest female cancer in the Somme region and represents the leading cause of cancer mortality in women. It therefore constitutes an important public health problem. From 1990 to 1993, 1,106 new cases of breast cancer were recorded by the Somme Cancer Registry. The incidence continued to increase over this period in the Somme region. The mortality rate for this period was 35.1/100,000 women, while the standardized mortality rate for the world population was 20.9/100,000 women. The most frequent histological types were invasive ductal carcinoma (64.3%) and invasive lobular carcinoma (5%). Carcinoma in situ represented 2.9% cases; 4% of patients presented metastases at the time of diagnosis. For the period 1990-1993, 44.3% cases were classified as T1, 37.9% as T2 and 11.5% as T3-T4. The lymph node extension rate was less than 15% for tumours less than 10 mm (on the resection specimen). The 5-year survival rate was 73%. It is important to increase the rate of early diagnosis in order to improve the overall survival of this disease.}, } @article {pmid11091760, year = {1996}, author = {Ohsumi, S and Nozaki, I and Takashima, S and Mandai, K}, title = {Invasive Ductal Carcinoma of the Nipple: A Case Report.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {3}, number = {3}, pages = {215-218}, pmid = {11091760}, issn = {1880-4233}, abstract = {We report a very rare case of breast carcinoma which possibly arose from the duct of the nipple and formed a nipple mass. A 71-year-old woman presented with an elastically hard and enlarged right nipple, 3.5x 2.8 cm in size. Mammograms and ultrasonograms suggested a benign tumor of the nipple, but histological examination revealed invasive ductal carcinoma. No Paget's cells were found in the epidermis. Modified radical mastectomy was performed. Both estrogen and progesterone receptors were positive. One of the nine axillary nodes dissected had metastatic foci. To our knowledge, this case is only the second reported case of invasive ductal carcinoma originating from the nipple. Differential diagnosis and histogenesis are discussed.}, } @article {pmid11091756, year = {1996}, author = {Arihiro, K and Kaneko, M and Suehiro, SI and Yamamoto, A and Kurihara, K and Takeda, S and Kuroi, K and Toge, T and Inai, K}, title = {Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {3}, number = {3}, pages = {181-198}, pmid = {11091756}, issn = {1880-4233}, abstract = {Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.}, } @article {pmid11667696, year = {1996}, author = {Abad, JL and Guardiola, M and Casas, J and Sánchez-Baeza, F and Messeguer, A}, title = {2,3,18,19-Dioxidosqualene Stereoisomers: Characterization and Activity as Inhibitors of Purified Pig Liver 2,3-Oxidosqualene-Lanosterol Cyclase.}, journal = {The Journal of organic chemistry}, volume = {61}, number = {21}, pages = {7603-7607}, doi = {10.1021/jo9607020}, pmid = {11667696}, issn = {1520-6904}, } @article {pmid12320022, year = {1996}, author = {Salazar, EL and Calzada, L and Pedron, N}, title = {Infiltrating ductal / lobular carcinoma: an evaluation of prognostic factors in primary breast cancer.}, journal = {Archives of AIDS research}, volume = {10}, number = {1-2}, pages = {73-82}, pmid = {12320022}, issn = {0899-4811}, mesh = {Americas ; Biology ; *Breast Neoplasms ; Developing Countries ; Disease ; Endocrine System ; *Estrogens ; *Histology ; Hormones ; Latin America ; Membrane Proteins ; *Menopause ; Mexico ; Neoplasms ; North America ; Physiology ; *Progesterone ; Progestins ; Reproduction ; *Research ; }, } @article {pmid11091533, year = {1995}, author = {Testempassi, E and Sakuma, T and Fukuda, Y and Murakami, Y and Harada, J and Tada, S and Suzuki, M}, title = {Solid Tubular Carcinoma of the Breast: MR Imaging and Pathologic Correlation.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {2}, number = {1}, pages = {59-63}, pmid = {11091533}, issn = {1880-4233}, abstract = {PURPOSE: Solid tubular carcinoma of the breast is a recognizable histologic type of invasive ductal carcinoma, characterized by rare axillary lymph nodal metastases and a good prognosis. The purpose of this study is to describe the magnetic resonance (MR) characteristics of solid tubular carcinoma and to emphasize the spotty appearance on the MR subtraction images. MATERIALS AND METHODS: We reviewed the MR findings of seven patients with biopsy-proven solid tubular carcinoma. Two of the 7 cases were of the pure type (more than 85% solid tubular component) and the remaining 5 were of the mixed type (50% to 85% solid tubular component). The mean age of the patients was 56 years. RESULTS: The mean size of the lesions was 28 mm. On T1-weighted images four of the lesions were visible and three were not identified. After Gd-DTPA all the lesions were enhanced. On the subtraction images, g" popcorn" appearence areas were noted in the stained mass. CONCLUSION: Our preliminary results suggest that solid tubular carcinomas have a characteristic apperarence on the subtraction MR images.}, } @article {pmid11091524, year = {1994}, author = {Fukutomi, T and Inoue, R and Ushijima, T and Tsuda, H and Adachi, I}, title = {Bilateral Breast Cancer in a Patient with a Strong Family History of Cancer: Analysis of p53 Germ Line Mutations.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {1}, number = {2}, pages = {151-155}, pmid = {11091524}, issn = {1880-4233}, abstract = {We report a case of bilateral breast carcinoma in a patient with a strong family history, including 4 cases of breast carcinoma, 1 case of prostate carcinoma (father), 1 case of hepatocellular carcinoma (mother), 2 cases of gastric carcinoma, 1 case of lung carcinoma, and 1 case of lingual carcinoma, in second degree relatives, together with analysis of germ line p53 mutations. The patient was a 51-year-old female who had undergone mastectomy 9 years previously for an invasive ductal carcinoma of the right breast. Lymph nodes were free of metastases and the tumor had negative estrogen receptor (ER) status. Bone and lung metastases developed 18 months after surgery, and had been well controlled with chemoendocrine therapy. She subsequently underwent a modified radical mastectomy for carcinoma in the contralateral breast. This was an invasive lobular carcinoma with negative lymph node metastasis, negative p53 immunoreaction, negative c-erbB-2 protein and positive ER status. In this breast-prostate carcinoma-type cancer family there was a high incidence of breast carcinoma; the father, who had prostate carcinoma, was possibly a carrier of a breast carcinoma susceptible gene. We have however detected to p53 germ line mutations in the lymphocytes DNA of the patient and her niece. The accumulation of cancers in this family line remains to be elucidated further using other genetic markers.}, } @article {pmid16667242, year = {1990}, author = {Longnecker, N and Welch, RM}, title = {Accumulation of apoplastic iron in plant roots : a factor in the resistance of soybeans to iron-deficiency induced chlorosis?.}, journal = {Plant physiology}, volume = {92}, number = {1}, pages = {17-22}, pmid = {16667242}, issn = {0032-0889}, abstract = {We hypothesized that the resistance of Hawkeye (HA) soybean (Glycine max L.) to iron-deficiency induced chlorosis (IDC) is correlated to an ability to accumulate a large pool of extracellular-root iron which can be mobilized to shoots as the plants become iron deficient. Iron in the root apoplast was assayed after efflux from the roots of intact plants in nutrient solution treated with sodium dithionite added under anaerobic conditions. Young seedlings of HA soybean accumulated a significantly larger amount of extracellular iron in their roots than did either IDC-susceptible PI-54619 (PI) soybean or IDC-resistant IS-8001 (IS) sunflower (Helianthus annus L.). Concurrently, HA soybean had much higher concentrations of iron in their shoots than either PI soybean or IS sunflower. The concentration of iron in the root apoplast and in shoots of HA soybean decreased sharply within days after the first measurements of extracellular root iron were made, in both +Fe and -Fe treatments. The accumulation of short-term iron reserves in the root apoplast and translocation of iron in large quantities to the shoot may be important characteristics of IDC resistance in soybeans.}, }